# Patent

## Title
Coleopteran-resistant transgenic plants and methods of their production

## Abstract

Disclosed are nucleic acid segments comprising synthetically-modified genes encoding Coleopteran-toxic B. thuringiensis δ-endotoxins. Also disclosed are methods of using these genes for the recombinant expression of polypeptides, the preparation of vectors containing the genes, and methods for transforming suitable host cells.

## Background
This application is a divisional of application Ser. No. 11/810,154, filed Jun. 4, 2007, now U.S. Pat. No. 7,544,862, which is a divisional of application Ser. No. 10/614,076, filed Jul. 3, 2003, now U.S. Pat. No. 7,227,056, which is a divisional of application Ser. No. 09/427,770, filed Oct. 27, 1999, now U.S. Pat. No. 6,620,988, which is a continuation of application Ser. No. 08/993,722, filed Dec. 18, 1997, now U.S. Pat. No. 6,060,594. All of the above priority documents are incorporated herewith by reference in their entirety.


1.0 BACKGROUND OF THE INVENTION
1.1 Field of the Invention
This invention relates to transformed host cells and vectors which comprise nucleic acid segments encoding genetically-engineered, recombinant Bacillus thuringiensis δ-endotoxins which are active against Coleopteran insects.
1.2 Description of the Related Art
Almost all field crops, plants, and commercial farming areas are susceptible to attack by one or more insect pests. Particularly problematic are Coleopteran and Lepidoptern pests. For example, vegetable and cole crops such as artichokes, kohlrabi, arugula, leeks, asparagus, lentils, beans, lettuce (e.g., head, leaf, romaine), beets, bok choy, malanga, broccoli, melons (e.g., muskmelon, watermelon, crenshaw, honeydew, cantaloupe), brussels sprouts, cabbage, cardoni, carrots, napa, cauliflower, okra, onions, celery, parsley, chick peas, parsnips, chicory, peas, chinese cabbage, peppers, collards, potatoes, cucumber, pumpkins, cucurbits, radishes, dry bulb onions, rutabaga, eggplant, salsify, escarole, shallots, endive, soybean, garlic, spinach, green onions, squash, greens, sugar beets, sweet potatoes, turnip, swiss chard, horseradish, tomatoes, kale, turnips, and a variety of spices are sensitive to infestation by one or more of the following insect pests: alfalfa looper, armyworm, beet armyworm, artichoke plume moth, cabbage budworm, cabbage looper, cabbage webworm, corn earworm, celery leafeater, cross-striped cabbageworm, european corn borer, diamondback moth, green cloverworm, imported cabbageworm, melonworm, omnivorous leafroller, pickleworm, rindworm complex, saltmarsh caterpillar, soybean looper, tobacco budworm, tomato fruitworm, tomato hornworm, tomato pinworm, velvetbean caterpillar, and yellowstriped armyworm. Likewise, pasture and hay crops such as alfalfa, pasture grasses and silage are often attacked by such pests as armyworm, beef armyworm, alfalfa caterpillar, European skipper, a variety of loopers and webworms, as well as yellowstriped armyworms.
Fruit and vine crops such as apples, apricots, cherries, nectarines, peaches, pears, plums, prunes, quince almonds, chestnuts, filberts, pecans, pistachios, walnuts, citrus, blackberries, blueberries, boysenberries, cranberries, currants, loganberries, raspberries, strawberries, grapes, avocados, bananas, kiwi, persimmons, pomegranate, pineapple, tropical fruits are often susceptible to attack and defoliation by achema sphinx moth, amorbia, armyworm, citrus cutworm, banana skipper, blackheaded fireworm, blueberry leafroller, cankerworm, cherry fruitworm, citrus cutworm, cranberry girdler, eastern tent caterpillar, fall webworm, fall webworm, filbert leafroller, filbert webworm, fruit tree leafroller, grape berry moth, grape leaffolder, grapeleaf skeletonizer, green fruitworm, gummosos-batrachedra commosae, gypsy moth, hickory shuckworm, hornworms, loopers, navel orangeworm, obliquebanded leafroller, omnivorous leafroller, omnivorous looper, orange tortrix, orangedog, oriental fruit moth, pandemis leafroller, peach twig borer, pecan nut casebearer, redbanded leafroller, red-humped caterpillar, roughskinned cutworm, saltmarsh caterpillar, spanworm, tent caterpillar, thecla-thecla basillides, tobacco budworm, tortrix moth, tufted apple budmoth, variegated leafroller, walnut caterpillar, western tent caterpillar, and yellowstriped armyworm.
Field crops such as canola/rape seed, evening primrose, meadow foam, corn (field, sweet, popcorn), cotton, hops, jojoba, peanuts, rice, safflower, small grains (barley, oats, rye, wheat, etc.), sorghum, soybeans, sunflowers, and tobacco are often targets for infestation by insects including armyworm, asian and other corn borers, banded sunflower moth, beet armyworm, bollworm, cabbage looper, corn rootworm (including southern and western varieties), cotton leaf perforator, diamondback moth, european corn borer, green cloverworm, headmoth, headworm, imported cabbageworm, loopers (including Anacamptodes spp.), obliquebanded leafroller, omnivorous leaftier, podworm, podworm, saltmarsh caterpillar, southwestern corn borer, soybean looper, spotted cutworm, sunflower moth, tobacco budworm, tobacco hornworm, velvetbean caterpillar,
Bedding plants, flowers, ornamentals, vegetables and container stock are frequently fed upon by a host of insect pests such as armyworm, azalea moth, beet armyworm, diamondback moth, ello moth (hornworm), Florida fern caterpillar, Io moth, loopers, oleander moth, omnivorous leafroller, omnivorous looper, and tobacco budworm.
Forests, fruit, ornamental, and nut-bearing trees, as well as shrubs and other nursery stock are often susceptible to attack from diverse insects such as bagworm, blackheaded budworm, browntail moth, california oakworm, douglas fir tussock moth, elm spanworm, fall webworm, fruittree leafroller, greenstriped mapleworm, gypsy moth, jack pine budworm, mimosa webworm, pine butterfly, redhumped caterpillar, saddleback caterpillar, saddle prominent caterpillar, spring and fall cankerworm, spruce budworm, tent caterpillar, tortrix, and western tussock moth. Likewise, turf grasses are often attacked by pests such as armyworm, sod webworm, and tropical sod webworm.
Because crops of commercial interest are often the target of insect attack, environmentally-sensitive methods for controlling or eradicating insect infestation are desirable in many instances. This is particularly true for farmers, nurserymen, growers, and commercial and residential areas which seek to control insect populations using eco-friendly compositions.
The most widely used environmentally-sensitive insecticidal formulations developed in recent years have been composed of microbial pesticides derived from the bacterium Bacillus thuringiensis. B. thuringiensis is a Gram-positive bacterium that produces crystal proteins or inclusion bodies which are specifically toxic to certain orders and species of insects. Many different strains of B. thuringiensis have been shown to produce insecticidal crystal proteins. Compositions including B. thuringiensis strains which produce insecticidal proteins have been commercially-available and used as environmentally-acceptable insecticides because they are quite toxic to the specific target insect, but are harmless to plants and other non-targeted organisms.
1.2.1 δ-Endotoxins
δ-endotoxins are used to control a wide range of leaf-eating caterpillars and beetles, as well as mosquitoes. These proteinaccous parasporal crystals, also referred to as insecticidal crystal proteins, crystal proteins, Bt inclusions, crystalline inclusions, inclusion bodies, and Bt toxins, are a large collection of insecticidal proteins produced by B. thuringiensis that are toxic upon ingestion by a susceptible insect host. Over the past decade research on the structure and function of B. thuringiensis toxins has covered all of the major toxin categories, and while these toxins differ in specific structure and function, general similarities in the structure and function are assumed. Based on the accumulated knowledge of B. thuringiensis toxins, a generalized mode of action for B. thuringiensis toxins has been created and includes: ingestion by the insect, solubilization in the insect midgut (a combination stomach and small intestine), resistance to digestive enzymes sometimes with partial digestion actually “activating” the toxin, binding to the midgut cells, formation of a pore in the insect cells and the disruption of cellular homeostasis (English and Slatin, 1992).
1.2.2 Genes Encoding Crystal Proteins
Many of the δ-endotoxins are related to various degrees by similarities in their amino acid sequences. Historically, the proteins and the genes which encode them were classified based largely upon their spectrum of insecticidal activity. The review by Höfte and Whiteley (1989) discusses the genes and proteins that were identified in B. thuringiensis prior to 1990, and sets forth the nomenclature and classification scheme which has traditionally been applied to B. thuringiensis genes and proteins: cryI genes encode lepidopterantoxic CryI proteins. cryII genes encode CryII proteins that are toxic to both lepidopterans and dipterans. cryIII genes encode coleopteran-toxic CryIII proteins, while cryIV genes encode dipteran-toxic CryIV proteins, etc. Based on the degree of sequence similarity, the proteins were further classified into subfamilies; more highly related proteins within each family were assigned divisional letters such as CryIA, CryIB, CryIC, etc. Even more closely related proteins within each division were given names such as CryIC1, CryIC2, etc.
Recently a new nomenclature was developed which systematically classifies the Cry proteins based upon amino acid sequence homology rather than upon insect target specificities. This classification scheme, including most of the known toxins but not including allelic variations in individual polypeptides, is summarized in Table 1.







TABLE 1







KNOWN B. THURINGIENSIS δ-ENDOTOXINS, GENBANK


ACCESSION NUMBERS, AND REVISED NOMENCLATUREA













GenBank



New
Old
Accession #






Cry1Aa1
CryIA(a)
M11250



Cry1Aa2
CryIA(a)
M10917



Cry1Aa3
CryIA(a)
D00348



Cry1Aa4
CryIA(a)
X13535



Cry1Aa5
CryIA(a)
D175182



Cry1Aa6
CryIA(a)
U43605



Cry1Ab1
CryIA(b)
M13898



Cry1Ab2
CryIA(b)
M12661



Cry1Ab3
CryIA(b)
M15271



Cry1Ab4
CryIA(b)
D00117



Cry1Ab5
CryIA(b)
X04698



Cry1Ab6
CryIA(b)
M37263



Cry1Ab7
CryIA(b)
X13233



Cry1Ab8
CryIA(b)
M16463



Cry1Ab9
CryIA(b)
X54939



Cry1Ab10
CryIA(b)
A29125



Cry1Ac1
CryIA(c)
M11068



Cry1Ac2
CryIA(c)
M35524



Cry1Ac3
CryIA(c)
X54159



Cry1Ac4
CryIA(c)
M73249



Cry1Ac5
CryIA(c)
M73248



Cry1Ac6
CryIA(c)
U43606



Cry1Ac7
CryIA(c)
U87793



Cry1Ac8
CryIA(c)
U87397



Cry1Ac9
CryIA(c)
U89872



Cry1Ac10
CryIA(c)
AJ002514



Cry1Ad1
CryIA(d)
M73250



Cry1Ae1
CryIA(e)
M65252



Cry1Ba1
CryIB
X06711



Cry1Ba2

X95704



Cry1Bb1
ET5
L32020



Cry1Bc1
CryIb(c)
Z46442



Cry1Bd1
CryE1
U70726



Cry1Ca1
CryIC
X07518



Cry1Ca2
CryIC
X13620



Cry1Ca3
CryIC
M73251



Cry1Ca4
CryIC
A27642



Cry1Ca5
CryIC
X96682



Cry1Ca6
CryIC
X96683



Cry1Ca7
CryIC
X96684



Cry1Cb1
CryIC(b)
M97880



Cry1Da1
CryID
X54160



Cry1Db1
PrtB
Z22511



Cry1Ea1
CryIE
X53985



Cry1Ea2
CryIE
X56144



Cry1Ea3
CryIE
M73252



Cry1Ea4

U94323



Cry1Eb1
CryIE(b)
M73253



Cry1Fa1
CryIF
M63897



Cry1Fa2
CryIF
M63897



Cry1Fb1
PrtD
Z22512



Cry1Ga1
PrtA
Z22510



Cry1Ga2
CryIM
Y09326



Cry1Gb1
CryH2
U70725



Cry1Ha1
PrtC
Z22513



Cry1Hb1

U35780



Cry1Ia1
CryV
X62821



Cry1Ia2
CryV
M98544



Cry1Ia3
CryV
L36338



Cry1Ia4
CryV
L49391



Cry1Ia5
CryV
Y08920



Cry1Ib1
CryV
U07642



Cry1Ja1
ET4
L32019



Cry1Jb1
ET1
U31527



Cry1Ka1

U28801



Cry2Aa1
CryIIA
M31738



Cry2Aa2
CryIIA
M23723



Cry2Aa3

D86084



Cry2Ab1
CryIIB
M23724



Cry2Ab2
CryIIB
X55416



Cry2Ac1
CryIIC
X57252



Cry3Aa1
CryIIIA
M22472



Cry3Aa2
CryIIIA
J02978



Cry3Aa3
CryIIIA
Y00420



Cry3Aa4
CryIIIA
M30503



Cry3Aa5
CryIIIA
M37207



Cry3Aa6
CryIIIA
U10985



Cry3Ba1
CryIIIB
X17123



Cry3Ba2
CryIIIB
A07234



Cry3Bb1
CryIIIB2
M89794



Cry3Bb2
CryIIIC(b)
U31633



Cry3Ca1
CryIIID
X59797



Cry4Aa1
CryIVA
Y00423



Cry4Aa2
CryIVA
D00248



Cry4Ba1
CryIVB
X07423



Cry4Ba2
CryIVB
X07082



Cry4Ba3
CryIVB
M20242



Cry4Ba4
CryIVB
D00247



Cry5Aa1
CryVA(a)
L07025



Cry5Ab1
CryVA(b)
L07026



Cry5Ba1
PS86Q3
U19725



Cry6Aa1
CryVIA
L07022



Cry6Ba1
CryVIB
L07024



Cry7Aa1
CryIIIC
M64478



Cry7Ab1
CryIIICb
U04367



Cry8Aa1
CryIIIE
U04364



Cry8Ba1
CryIIIG
U04365



Cry8Ca1
CryIIIF
U04366



Cry9Aa1
CryIG
X58120



Cry9Aa2
CryIG
X58534



Cry9Ba1
CryIX
X75019



Cry9Ca1
CryIH
Z37527



Cry9Da1
N141
D85560



Cry10Aa1
CryIVC
M12662



Cry11Aa1
CryIVD
M31737



Cry11Aa2
CryIVD
M22860



Cry11Ba1
Jeg80
X86902



Cry12Aa1
CryVB
L07027



Cry13Aa1
CryVC
L07023



Cry14Aa1
CryVD
U13955



Cry15Aa1
34 kDa
M76442



Cry16Aa1
cbm71
X94146



Cry17Aa1
cbm71
X99478



Cry18Aa1
CryBP1
X99049



Cry19Aa1
Jeg65
Y08920



Cry20Aa1

U82518



Cry21Aa1

I32932



Cry22Aa1

I34547



Cyt1Aa1
CytA
X03182



Cyt1Aa2
CytA
X04338



Cyt1Aa3
CytA
Y00135



Cyt1Aa4
CytA
M35968



Cyt1Ab1
CytM
X98793



Cyt1Ba1

U37196



Cyt2Aa1
CytB
Z14147



Cyt2Ba1
“CytB”
U52043



Cyt2Ba2
“CytB”
AF020789



Cyt2Ba3
“CytB”
AF022884



Cyt2Ba4
“CytB”
AF022885



Cyt2Ba5
“CytB”
AF022886



Cyt2Bb1

U82519





aAdapted from: http://epunix.biols.susx.ac.uk/Home/Neil_Crickmore/Bt/index.html






1.2.3 Bioinsecticide Polypeptide Compositions

The utility of bacterial crystal proteins as insecticides was extended beyond lepidopterans and dipteran larvae when the first isolation of a coleopteran-toxic B. thuringiensis strain was reported (Krieg et al., 1983; 1984). This strain (described in U.S. Pat. No. 4,766,203, specifically incorporated herein by reference), designated B. thuringiensis var. tenebrionis, is reported to be toxic to larvae of the coleopteran insects Agelastica alni (blue alder leaf beetle) and Leptinotarsa decemlineata (Colorado potato beetle).
U.S. Pat. No. 5,024,837 also describes hybrid B. thuringiensis var. kurstaki strains which showed activity against lepidopteran insects. U.S. Pat. No. 4,797,279 (corresponding to EP 0221024) discloses a hybrid B. thuringiensis containing a plasmid from B. thuringiensis var. kurstaki encoding a lepidopteran-toxic crystal protein-encoding gene and a plasmid from B. thuringiensis tenebrionis encoding a coleopteran-toxic crystal protein-encoding gene. The hybrid B. thuringiensis strain produces crystal proteins characteristic of those made by both B. thuringiensis kurstaki and B. thuringiensis tenebrionis. U.S. Pat. No. 4,910,016 (corresponding to EP 0303379) discloses a B. thuringiensis isolate identified as B. thuringiensis MT 104 which has insecticidal activity against coleopterans and lepidopterans.
1.2.4 Molecular Genetic Techniques Facilitate Protein Engineering
The revolution in molecular genetics over the past decade has facilitated a logical and orderly approach to engineering proteins with improved properties. Site specific and random mutagenesis methods, the advent of polymerase chain reaction (PCRTM) methodologies, and related advances in the field have permitted an extensive collection of tools for changing both amino acid sequence, and underlying genetic sequences for a variety of proteins of commercial, medical, and agricultural interest.
Following the rapid increase in the number and types of crystal proteins which have been identified in the past decade, researchers began to theorize about using such techniques to improve the insecticidal activity of various crystal proteins. In theory, improvements to δ-endotoxins should be possible using the methods available to protein engineers working in the art, and it was logical to assume that it would be possible to isolate improved variants of the wild-type crystal proteins isolated to date. By strengthening one or more of the aforementioned steps in the mode of action of the toxin, improved molecules should provide enhanced activity, and therefore, represent a breakthrough in the field. If specific amino acid residues on the protein are identified to be responsible for a specific step in the mode of action, then these residues can be targeted for mutagenesis to improve performance
1.2.5 Structural Analyses of Crystal Proteins
The combination of structural analyses of B. thuringiensis toxins followed by an investigation of the function of such structures, motifs, and the like has taught that specific regions of crystal protein endotoxins are, in a general way, responsible for particular functions.
Domain 1, for example, from Cry3Bb and Cry1Ac has been found to be responsible for ion channel activity, the initial step in formation of a pore (Walters et al., 1993; Von Tersch et al., 1994). Domains 2 and 3 have been found to be responsible for receptor binding and insecticidal specificity (Aronson et al., 1995; Caramori et al., 1991; Chen et al. 1993; de Maagd et al., 1996; Ge et al., 1991; Lee et al., 1992; Lee et al., 1995; Lu et al., 1994; Smedley and Ellar, 1996; Smith and Ellar, 1994; Rajamohan et al., 1995; Rajamohan et al., 1996; Wu and Dean, 1996). Regions in domain 2 and 3 can also impact the ion channel activity of some toxins (Chen et al., 1993, Wolfersberger et al., 1996; Von Fersch et al., 1994).
1.3 Deficiencies in the Prior Art
Unfortunately, while many laboratories have attempted to make mutated crystal proteins, few have succeeded in making mutated crystal proteins with improved lepidopteran toxicity. In almost all of the examples of genetically-engineered B. thuringiensis toxins in the literature, the biological activity of the mutated crystal protein is no better than that of the wild-type protein, and in many cases, the activity is decreased or destroyed altogether (Almond and Dean, 1993; Aronson et al., 1995; Chen et al., 1993, Chen et al., 1995; Ge et al., 1991; Kwak et al., 1995; Lu et al., 1994; Rajamohan et al., 1995; Rajamohan et al., 1996; Smedley and Ellar, 1996; Smith and Ellar, 1994; Wolfersberger et al., 1996; Wu and Aronson, 1992).
For a crystal protein having approximately 650 amino acids in the sequence of its active toxin, and the possibility of 20 different amino acids at each position in this sequence, the likelihood of arbitrarily creating a successful new structure is remote, even if a general function to a stretch of 250-300 amino acids can be assigned. Indeed, the above prior art with respect to crystal protein gene mutagenesis has been concerned primarily with studying the structure and function of the crystal proteins, using mutagenesis to perturb some step in the mode of action, rather than with engineering improved toxins.
Collectively, the limited successes in the art to develop synthetic toxins with improved insecticidal activity have stifled progress in this area and confounded the search for improved endotoxins or crystal proteins. Rather than following simple and predictable rules, the successful engineering of an improved crystal protein may involve different strategies, depending on the crystal protein being improved and the insect pests being targeted. Thus, the process is highly empirical.
Accordingly, traditional recombinant DNA technology is clearly not routine experimentation for providing improved insecticidal crystal proteins. What are lacking in the prior art are rational methods for producing genetically-engineered B. thuringiensis crystal proteins that have improved insecticidal activity and, in particular, improved toxicity towards a wide range of lepidopteran insect pests.
2.0 SUMMARY OF THE INVENTION
The present invention seeks to overcome these and other drawbacks inherent in the prior art by providing genetically-engineered modified B. thuringiensis δ-endotoxins (Cry*), and in particular modified Cry3 δ-endotoxins (designated Cry3* endotoxins). Also provided are nucleic acid sequences comprising one or more genes which encode such modified proteins. Particularly preferred genes include cry3* genes such as cry3A*, cry3B*, and cry3C* genes, particularly cry3B* genes, and more particularly, cry3Bb* genes, that encode modified crystal proteins having improved insecticidal activity against target pests.
Also disclosed are novel methods for constructing synthetic Cry3* proteins, synthetically-modified nucleic acid sequences encoding such proteins, and compositions arising therefrom. Also provided are synthetic cry3* expression vectors and various methods of using the improved genes and vectors. In a preferred embodiment, the invention discloses and claims Cry3B* proteins and cry3B* genes which encode improved insecticidal polypeptides.
In preferred embodiments, channel-forming toxin design methods are disclosed which have been used to produce a specific set of designed Cry3Bb* toxins with improved biological activity. These improved Cry3Bb* proteins are listed in Table 2 along with their respective amino acid changes from wild-type (WT) Cry3Bb, the nucleotide changes present in the altered cry3Bb* gene encoding the protein, the fold increase in bioactivity over WT Cry3Bb, the structural site of the alteration, and the design method(s) used to create the new toxins.
Accordingly, the present invention provides in an overall and general sense, mutagenized Cry3 protein-encoding genes and methods of making and using such genes. As used herein the term “mutagenized cry3 gene(s)” means one or more cry3 genes that have been mutagenized or altered to contain one or more nucleotide sequences which are not present in the wild type sequences, and which encode mutant Cry3 crystal proteins (Cry3*) showing improved insecticidal activity. Such mutagenized cry3 genes have been referred to in the Specification as cry3* genes. Exemplary cry3* genes include cry3A*, cry3B*, and cry3C* genes.
Exemplary mutagenized Cry3 protein-encoding genes include cry3B genes. As used herein the term “mutagenized cry3B gene(s)” means one or more genes that have been mutagenized or altered to contain one or more nucleotide sequences which are not present in the wild type sequences, and which encode mutant Cry3B crystal proteins (Cry3B*) showing improved insecticidal activity. Such genes have been designated cry3B* genes. Exemplary cry3B* genes include cry3Ba* and cry3Bb* genes, which encode Cry3Ba* and Cry3Bb* proteins, respectively.
Likewise, the present invention provides mutagenized Cry3A protein-encoding genes and methods of making and using such genes. As used herein the term “mutagenized cry3A gene(s)” means one or more genes that have been mutagenized or altered to contain one or more nucleotide sequences which are not present in the wild type sequences, and which encode mutant Cry3A crystal proteins (Cry3A*) showing improved insecticidal activity. Such mutagenized genes have been designated as cry3A* genes.
In similar fashion, the present invention provides mutagenized Cry3C protein-encoding genes and methods of making and using such genes. As used herein the term “mutagenized cry3C gene(s)” means one or more genes that have been mutagenized or altered to contain one or more nucleotide sequences which are not present in the wild type sequences, and which encode mutant Cry3C crystal proteins (Cry3C*) showing improved insecticidal activity. Such mutagenized genes have been designated as cry3C* genes.
Preferably the novel sequences comprise nucleic acid sequences in which at least one, and preferably, more than one, and most preferably, a significant number, of wild-type cry3 nucleotides have been replaced with one or more nucleotides, or where one or more nucleotides have been added to or deleted from the native nucleotide sequence for the purpose of altering, adding, or deleting the corresponding amino acids encoded by the nucleic acid sequence so mutagenized. The desired result, therefore, is alteration of the amino acid sequence of the encoded crystal protein to provide toxins having improved or altered activity and/or specificity compared to that of the unmodified crystal protein.
Examples of preferred Cry2Bb*-encoding genes include cry3Bb.60, cry3Bb.11221, cry3Bb.11222, cry3Bb.11223, cry3Bb.11224, cry3Bb.11225, cry3Bb.11226, cry3Bb.11227, cry3Bb.11228, cry3Bb.11229, cry3Bb.11230, cry3Bb.11231, cry3Bb.11232, cry3Bb.11233, cry3Bb.11234, cry3Bb.11235, cry3Bb.11236, cry3Bb.11237, cry3Bb.11238, cry3Bb.11239, cry3Bb.11241, cry3Bb.11242, cry3Bb.11032, cry3Bb.11035, cry3Bb.11036, cry3Bb.11046, cry3Bb.11048, cry3Bb.11051, cry3Bb.11057, cry3Bb.11058, cry3Bb.11081, cry3Bb.11082, cry3Bb.11083, cry3Bb.11084, cry3Bb.11095, and cry3Bb.11098.







TABLE 2







CRY3BB* PROTEINS EXHIBITING IMPROVED ACTIVITY AGAINST SCRW LARVAE













Cry3Bb*
cry3Bb*



Fold
Design


Protein
Plasmid
cry3Bb* Nucleotide Sequence
Cry3Bb* Amino
Structural Site
Increase Over
Method


Designation
Designation
Changes
Acid Changes
of Changes
WT Activity
Used





Cry3Bb.60
—
—
Δ1-159
Δα1-α3
3.6×
1, 6, 8


Cry3Bb.11221
pEG1707
A460T, C461T, A462T, C464A,
T154F, P155H,
1α3, 4
6.4×
1, 8




T465C, T466C, T467A, A468T,
L156H, L158R







A469T, G470C, T472C, T473G,








G474T, A477T, A478T, G479C






Cry3Bb.11222
pEG1708
T687C, T688C, A689T, C691A,
Y230L, H231S
α6
4.0×
3, 7




A692G






Cry3Bb.11223
pEG1709
T667C, T687C, T688A, A689G,
S223P, Y230S
α6
2.8×
3




C691A, A692G






Cry3Bb.11224
pEG1710
T687C, A692G
H231R
α6
5.0×
7, 8


Cry3Bb.11225
pEG1711
T687C, C691A
H231N, T241S
α6
3.6×
7


Cry3Bb.11226
pEG1712
T687C, C691A, A692C, T693C
H231T
α6
3.0×
7, 8


Cry3Bb.11227
pEG1713
C868A, G869A, G870T
R290N
1α7, β1
1.9×
2, 3, 4 6


Cry3Bb.11228
pEG1714
C932T, A938C, T942G, G949A,
S311L, N313T,
1β1, α8
4.1×
2, 4




T954C
E317K





Cry3Bb.11229
pEG1715
T931A, A933C, T942A, T945A,
S311T, E317K,
1β1, α8
2.5×
2, 4




G949A, A953G, T954C
Y318C





Cry3Bb.11230
pEG1716
T931G, A933C, C934G, T945G,
S311A, L312V,
1β1, α8
4.7×
2, 4 8




C946T, A947G, G951A, T954C
Q316W





Cry3Bb.11231
pEG1717
T687C, A692G, C932T, A938C,
H231R, S311L,
α6; 1β1, α8
7.9×
2, 4, 7, 8,




T942G, G949A, T954C
N313T, E317K


10


Cry3Bb.11232
pEG1718
T931A, A933G, T935C, T936A,
S311T, L312P,
1β1, α8
5.1×
4




A938C, T939C, T942C, T945A,
N313T, E317N







G951T, T954C






Cry3Bb.11233
pEG1719
T931G, A933C, T936G, T942C,
S311A, Q316D
1β1, α8
2.2×
2, 4




C943T, T945A, C946G, G948C,








T954C






Cry3Bb.11234
pEG1720
T861C, T866C, C868A, T871C,
I289T, L291R,
1α7, β1
4.1×
4




T872G, A875T, T877A, C878G,
Y292F, S293R







A882G






Cry3Bb.11235
pEG1721
T687C, A692G, C932T
H231R, S311L
α6; 1β1, α8
3.2×
2, 4, 7, 8,








10


Cry3Bb.11236
pEG1722
T931A, C932T, A933C, T936C,
S311I
1β1, α8
3.1×
2, 4




T942G, T945A, T954C






Cry3Bb.11237
pEG1723
T931A, C932T, A933C, T936C,
S311I, N313H
1β1, α8
5.4×
2, 4




A937G, A938T, C941A, T942C,








T945A, C946A, A947T, A950T,








T954C






Cry3Bb.11238
pEG1724
A933C, T936C, A937G, A938T,
N313V, T314N,
1β1, α8
2.6×
2, 4




C941A, T942C, T945A, C946A,
Q316M, E317V







A947T, A950T, T954C






Cry3Bb.11239
pEG1725
A933T, A938G, T939G, T942A,
N313R, L315P,
1β1, α8
2.8×
2, 4




T944C, T945A, A947T, G948T,
Q316L, E317A







A950C, T954C






Cry3Bb.11241
pEG1726
A860T, T861C, G862A, C868T,
Y287F, D288N,
1α7, β1
2.6×
2, 3, 4, 6




G869T, T871C, A873T, T877A,
R290L







C878G, A879T






Cry3Bb.11242
pEG1727
C868G, G869T
R290V
1α7, β1
2.5×
2, 3, 4, 6, 8


Cry3Bb.11032
pEG1041
A494G
D165G
α4
3.1×
2, 4, 8


Cry3Bb.11035
pEG1046
G479A, A481C, A482C,
S160N, K161P,
α4
2.7×
8




A484C, G485A, A486C, A494G
R162H, D165G





Cry3Bb.11036
pEG1047
A865G, T877C
I289V, S293P
1α7, β1
4.3×
4


Cry3Bb.11046
pEG1052
G479A, A481C, A482C,
S160N, K161P,
α4; 1α7, β1
2.6×
2, 4, 8, 10




A484C, G485A, A486C,
R162H, D165G,







A494G, A865G, T877C
I289V, S293P





Cry3Bb.11048
pEG1054
T309A, Δ310, Δ311, Δ312
D103E, ΔA104
1α2a, 2b
4.3×
8


Cry3Bb.11051
pEG1057
A565G, A566G
K189G
1α4, 5
3.0×
2, 3, 4


Cry3Bb.11057
pEG1062
T309A, Δ310, Δ311, Δ312,
D103E, ΔA104,
1α2a, 2b; α4
3.4×
2, 4, 8, 10




G479A, A481C, A482C,
S160N, K161P,







A484C, G485A, A486C, A494G
R162H, D165G





Cry3Bb.11058
pEG1063
T309A, Δ310, Δ311, Δ312,
D103E, ΔA104,
1α2a, 2b; 1α3, 4
3.5×
1, 8, 10




A460T, C461T, A462T, C464A,
T154F, P155H,







T465C, T466C, T467A, A468T,
L156H, L158R







A469T, G470C, T472C, T473G,








G474T, A477T, A478T, G479C






Cry3Bb.11081
pEG1084
A494G, T931A, A933C, T942A,
D165G, S311T,
α4; 1β1, α8
6.1×
2, 4, 8, 10




T945A, G949A, T954C
E317K





Cry3Bb.11082
pEG1085
A494G, A865G, T877C, T914C,
D165G, I289V,
α4; 1α7, β1; β1;
4.9×
2, 4, 5, 8,




T931G, A933C, C934G, T945G,
S293P, F305S,
1β1, α8; β2;

9, 10




C946T, A947G, G951A, T954C,
S311A, L312V,
β3b






A1043G, T1094C
Q316W, Q348R,








V365A





Cry3Bb.11083
pEG1086
A865G, T877C, A1043G
I289V, S293P,
1α7, β1; β2
7.4×
4, 5, 9, 10





Q348R





Cry3Bb.11084
pEG1087
A494G, C932T
D165G, S311L
α4; 1β1, α8
7.2×
2, 4, 8, 10


Cry3Bb.11095
pEG1095
A1043G
Q348R
β2
4.6×
5, 9


Cry3Bb.11098
pEG1098
A494G, T687C, A692G, C932T,
D165G, I1231R,
α4; α6, 1β1, α8
7.9×
2, 4, 7, 8




A938C, T942G, G949A, T954C
S311L, N313T,








E317K









In a variety of illustrative embodiments, the inventors have shown remarkable success in generating toxins with improved insecticidal activity using these methods. In particular, the inventors have identified unique methods of analyzing and designing toxins having improved or enhanced insecticidal properties both in vitro and in vivo.
In addition to modifications of Cry3Bb peptides, those having benefit of the present teaching are now also able to make mutations in a variety of channel-forming toxins, and particularly in crystal proteins which are related to Cry3Bb either functionally or structurally. In fact, the inventors contemplate that any B. thuringiensis crystal protein or peptide can be analyzed using the methods disclosed herein and may be altered using the methods disclosed herein to produce crystal proteins having improved insecticidal specificity or activity. Alternatively, the inventors contemplate that those of skill in the art having the benefit of the teachings disclosed herein will be able to prepare not only mutated Cry3 toxins with improved activity, but also other crystal proteins including all of those proteins identified in Table 1, herein. In particular, the inventors contemplate the creation of Cry3* variants using one or more of the methods disclosed herein to produce toxins with improved activity. For example, the inventors note Cry3A, Cry3B, and Cry3C crystal proteins (which are known in the art) may be modified using one or more of the design strategies employed herein, to prepare synthetically-modified crystal proteins with improved properties. Likewise, one of skill in the art will even be able to utilize the teachings of the present disclosure to modify other channel forming toxins, including channel forming toxins other than B. thuringiensis crystal proteins, and even to modify proteins and channel toxins not yet described or characterized.
Because the structures for insecticidal crystal proteins show a remarkable conservation of protein tertiary structure (Grochulski et al., 1995), and because many crystal proteins show significant amino acid sequence identity to the Cry3Bb amino acid sequence within domain 1, including proteins of the Cry1, Cry2, Cry3, Cry4, Cry5, Cry7, Cry8, Cry9, Cry10, Cry11, Cry12, Cry13, Cry14, and Cry16 classes (Table 1), now in light of the inventors' surprising discovery, for the first time, those of skill in the art having benefit of the teachings disclosed herein will be able to broadly apply the methods of the invention to modifying a host of crystal proteins with improved activity or altered specificity. Such methods will not only be limited to the insecticidal crystal proteins disclosed in Table 1, but may also been applied to any other related crystal protein, including those yet to be identified.
In particular, the high degree of homology between Cry3A, Cry3B, and Cry3C proteins is evident in the alignment of the primary amino acid sequence of the three proteins (FIG. 17A, FIG. 17B, and FIG. 17C).
As such, the disclosed methods may be now applied to preparation of modified crystal proteins having one or more alterations introduced using one or more of the mutational design methods as disclosed herein. The inventors further contemplate that regions may be identified in one or more domains of a crystal protein, or other channel forming toxin which may be similarly modified through site-specific or random mutagenesis to generate toxins having improved activity, or alternatively, altered specificity.
In certain applications, the creation of altered toxins having increased activity against one or more insects is desired. Alternatively, it may be desirable to utilize the methods described herein for creating and identifying altered insecticidal crystal proteins which are active against a wider spectrum of susceptible insects. The inventors further contemplate that the creation of chimeric insecticidal crystal proteins comprising one or more of these mutations may be desirable for preparing “super” toxins which have the combined advantages of increased insecticidal activity and concomitant broad spectrum activity.
In light of the present disclosure, the mutagenesis of one or more codons within the sequence of a toxin may result in the generation of a host of related insecticidal proteins having improved activity. While exemplary mutations have been described for each of the design strategies employed in the present invention, the inventors contemplate that mutations may also be made in insecticidal crystal proteins, including the loop regions, helices regions, active sites of the toxins, regions involved in protein oligomerization, and the like, which will give rise to functional bioinsecticidal crystal proteins. All such mutations are considered to fall within the scope of this disclosure.
In one illustrative embodiment, mutagenized cry3Bb* genes are obtained which encode Cry3Bb* variants that are generally based upon the wild-type Cry3Bb sequence, but that have one or more changes incorporated into the amino acid sequence of the protein using one or more of the design strategies described and claimed herein.
In these and other embodiments, the mutated genes encoding the crystal proteins may be modified so as to change about one, two, three, four, or five or so amino acids in the primary sequence of the encoded polypeptide. Alternatively even more changes from the native sequence may be introduced, such that the encoded protein may have at least about 1% or 2%, or alternatively about 3% or about 4%, or even about 5% to about 10%, or about 10% to about 15%, or even about 15% to about 20% or more of the codons either altered, deleted, or otherwise modified. In certain situations, it may even be desirable to alter substantially more of the primary amino acid sequence to obtain the desired modified protein. In such cases the inventors contemplate that from about 25%, to about 50%, or even from about 50% to about 75%, or more of the native (or wild-type) codons either altered, deleted, or otherwise modified. Alternatively, mutations in the amino acid sequences or underlying DNA gene sequences which result in the insertion or deletion of one or more amino acids within one or more regions of the crystal protein or peptide.
To effect such changes in the primary sequence of the encoded polypeptides, it may be desirable to mutate or delete one or more nucleotides from the nucleic acid sequences of the genes encoding such polypeptides, or alternatively, under certain circumstances to add one or more nucleotides into the primary nucleic acid sequence at one or more sites in the sequence. Frequently, several nucleotide residues may be altered to produce the desired polypeptide. As such, the inventors contemplate that in certain embodiments it may be desirable to alter only one, two, three, four, or five or so nucleotides in the primary sequence. In other embodiments, which more changes are desired, the mutagenesis may involve changing, deleting, or inserting 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or even 20 or so nucleotide residues in the gene sequence. In still other embodiments, one may desire to mutate, delete, or insert 21, 22, 23, 24, 25, 26, 27, 28, 29, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, or even 90-100, 150, 200, 250, 300, 350, 400, 450, or more nucleotides in the sequence of the gene in order to prepare a cry3* gene which produces a Cry3* polypeptide having the desired characteristics. In fact, any number of mutations, deletions, and/or insertions may be made in the primary sequence of the gene, so long as the encoded protein has the improved insecticidal activity or specificity characteristics described herein.
Changing a large number of the codons in the nucleotide sequence of an endotoxin-encoding gene may be particularly desirable and often necessary to achieve the desired results, particularly in the situation of “plantizing” a DNA sequence in order to express a DNA of non-plant origin in a transformed plant cell. Such methods are routine to those of skill in the plant genetics arts, and frequently many residues of a primary gene sequence will be altered to facilitate expression of the gene in the plant cell. Preferably, the changes in the gene sequence introduce no changes in the amino acid sequence, or introduce only conservative replacements in the amino acid sequence such that the polypeptide produced in the plant cell from the “plantized” nucleotide sequence is still fully functional, and has the desired qualities when expressed in the plant cell.
Genes and encoded proteins mutated in the manner of the invention may also be operatively linked to other protein-encoding nucleic acid sequences, or expressed as fusion proteins. Both N-terminal and C-terminal fusion proteins are contemplated. Virtually any protein- or peptide-encoding DNA sequence, or combinations thereof, may be fused to a mutated cry3* sequence in order to encode a fusion protein. This includes DNA sequences that encode targeting peptides, proteins for recombinant expression, proteins to which one or more targeting peptides is attached, protein subunits, domains from one or more crystal proteins, and the like. Such modifications to primary nucleotide sequences to enhance, target, or optimize expression of the gene sequence in a particular host cell, tissue, or cellular localization, are well-known to those of skill in the art of protein engineering and molecular biology, and it will be readily apparent to such artisans, having benefit of the teachings of this specification, how to facilitate such changes in the nucleotide sequence to produce the polypeptides and polynucleotides disclosed herein.
In one aspect, the invention discloses and claims host cells comprising one or more of the modified crystal proteins disclosed herein, and in particular, cells of B. thuringiensis strains EG11221, EG11222, EG11223, EG11224, EG11225, EG11226, EG11227, EG11228, EG11229, EG11230, EG11231, EG11232, EG11233, EG11234, EG11235, EG11236, EG11237, EG11238, EG11239, EG11241, EG11242, EG11032, EG11035, EG11036, EG11046, EG11048, EG11051, EG11057, EG11058, EG11081. EG11082, EG11083, EG11084, EG11095, and EG11098 which comprise recombinant DNA segments encoding synthetically-modified Cry3Bb* crystal proteins which demonstrates improved insecticidal activity.
Likewise, the invention also discloses and claims cell cultures of B. thuringiensis EG11221, EG11222, EG11223, EG11224, EG11225, EG11226, EG11227, EG11228, EG11229, EG11230, EG11231, EG11232, EG11233, EG11234, EG11235, EG11236, EG11237, EG11238, EG11239, EG11241, EG11242, EG11032, EG11035, EG11036, EG11046, EG11048, EG11051, EG11057, EG11058, EG11081, EG11082, EG11083, EG11084, and EG11095, and 11098.
Such cell cultures may be biologically-pure cultures consisting of a single strain, or alternatively may be cell co-cultures consisting of one or more strains. Such cell cultures may be cultivated under conditions in which one or more additional B. thuringiensis or other bacterial strains are simultaneously co-cultured with one or more of the disclosed cultures, or alternatively, one or more of the cell cultures of the present invention may be combined with one or more additional B. thuringiensis or other bacterial strains following the independent culture of each. Such procedures may be useful when suspensions of cells containing two or more different crystal proteins are desired.
The subject cultures have been deposited under conditions that assure that access to the cultures will be available during the pendency of this patent application to one determined by the Commissioner of Patents and Trademarks to be entitled thereto under 37 C.F.R. §1.14 and 35 U.S.C. §122. The deposits are available as required by foreign patent laws in countries wherein counterparts of the subject application, or its progeny, are filed. However, it should be understood that the availability of a deposit does not constitute a license to practice the subject invention in derogation of patent rights granted by governmental action.
Further, the subject culture deposits will be stored and made available to the public in accord with the provisions of the Budapest Treaty for the Deposit of Microorganisms, i.e., they will be stored with all the care necessary to keep them viable and uncontaminated for a period of at least five years after the most recent request for the finishing of a sample of the deposit, and in any case, for a period of at least 30 (thirty) years after the date of deposit or for the enforceable life of any patent which may issue disclosing the cultures. The depositor acknowledges the duty to replace the deposits should the depository be unable to furnish a sample when requested, due to the condition of the deposits. All restrictions on the availability to the public of the subject culture deposits will be irrevocably removed upon the granting of a patent disclosing them.
Cultures shown in Table 3 were deposited in the permanent collection of the Agricultural Research Service Culture Collection, Northern Regional Research Laboratory (NRRL) under the terms of the Budapest Treaty.







TABLE 3







STRAINS OF THE PRESENT INVENTION DEPOSITED


UNDER THE TERMS OF THE BUDAPEST TREATY













Accession Number


Strain
Deposit Date
Protein
(NRRL Number)





EG11032
May 27, 1997
Cry3Bb.11032
B-21744


EG11035
May 27, 1997
Cry3Bb.11035
B-21745


EG11036
May 27, 1997
Cry3Bb.11036
B-21746


EG11037
May 27, 1997
Cry3Bb.11037
B-21747


EG11046
May 27, 1997
Cry3Bb.11046
B-21748


EG11048
May 27, 1997
Cry3Bb.11048
B-21749


EG11051
May 27, 1997
Cry3Bb.11051
B-21750


EG11057
May 27, 1997
Cry3Bb.11057
B-21751


EG11058
May 27, 1997
Cry3Bb.11058
B-21752


EG11081
May 27, 1997
Cry3Bb.11081
B-21753


EG11082
May 27, 1997
Cry3Bb.11082
B-21754


EG11083
May 27, 1997
Cry3Bb.11083
B-21755


EG11084
May 27, 1997
Cry3Bb.11084
B-21756


EG11095
May 27, 1997
Cry3Bb.11095
B-21757


EG11204
May 27, 1997
Cry3Bb.11204
B-21758


EG11221
May 27, 1997
Cry3Bb.11221
B-21759


EG11222
May 27, 1997
Cry3Bb.11222
B-21760


EG11223
May 27, 1997
Cry3Bb.11223
B-21761


EG11224
May 27, 1997
Cry3Bb.11224
B-21762


EG11225
May 27, 1997
Cry3Bb.11225
B-21763


EG11226
May 27, 1997
Cry3Bb.11226
B-21764


EG11227
May 27, 1997
Cry3Bb.11227
B-12765


EG11228
May 27, 1997
Cry3Bb.11228
B-12766


EG11229
May 27, 1997
Cry3Bb.11229
B-21767


EG11230
May 27, 1997
Cry3Bb.11230
B-21768


EG11231
May 27, 1997
Cry3Bb.11231
B-21769


EG11232
May 27, 1997
Cry3Bb.11232
B-12770


EG11233
May 27, 1997
Cry3Bb.11233
B-21771


EG11234
May 27, 1997
Cry3Bb.11234
B-21772


EG11235
May 27, 1997
Cry3Bb.11235
B-21773


EG11236
May 27, 1997
Cry3Bb.11236
B-21774


EG11237
May 27, 1997
Cry3Bb.11237
B-21775


EG11238
May 27, 1997
Cry3Bb.11238
B-21776


EG11239
May 27, 1997
Cry3Bb.11239
B-21777


EG11241
May 27, 1997
Cry3Bb.11241
B-21778


EG11242
May 27, 1997
Cry3Bb.11242
B-21779









Also disclosed are methods of controlling or eradicating an insect population from an environment. Such methods generally comprise contacting the insect population to be controlled or eradicated with an insecticidally-effective amount of a Cry3* crystal protein composition. Preferred Cry3* compositions include Cry3A*, Cry3B*, and Cry3C* polypeptide compositions, with Cry3B* compositions being particularly preferred. Examples of such polypeptides include proteins selected from the group consisting of Cry3Bb-60, Cry3Bb.11221, Cry3Bb.11222, Cry3Bb.11223, Cry3Bb.11224, Cry3Bb.11225, Cry3Bb.11226, Cry3Bb.11227, Cry3Bb.11228, Cry3Bb.11229, Cry3Bb.11230, Cry3Bb.11231, Cry3Bb.11232, Cry3Bb.11233, Cry3Bb.11234, Cry3Bb.11235, Cry3Bb.11236, Cry3Bb.11237, Cry3Bb.11238, Cry3Bb.11239, Cry3Bb.11241, Cry3Bb.11242, Cry3Bb.11032, Cry3Bb.11035, Cry3Bb.11036, Cry3Bb.11046, Cry3Bb.11048, Cry3Bb.11051, Cry3Bb.11057, Cry3Bb.11058, Cry3Bb.11081, Cry3Bb.11082, Cry3Bb.11083, Cry3Bb.11084, Cry3Bb.11095, and Cry3Bb.11098.
In preferred embodiments, these Cry3Bb* crystal protein compositions comprise the amino acid sequence of any of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6. SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14. SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102 or SEQ ID NO:108.
2.1 Methods for Producing Modified Cry* Proteins
The modified Cry* polypeptides of the present invention are preparable by a process which generally involves the steps of obtaining a nucleic acid sequence encoding a Cry* polypeptide; analyzing the structure of the polypeptide to identify particular “target” sites for mutagenesis of the underlying gene sequence; introducing one or more mutations into the nucleic acid sequence to produce a change in one or more amino acid residues in the encoded polypeptide sequence; and expressing in a transformed host cell the mutagenized nucleic acid sequence under conditions effective to obtain the modified Cry* protein encoded by the cry* gene.
Means for obtaining the crystal structures of the polypeptides of the invention are well-known. Exemplary high resolution crystal structure solution sets are given in Section 9.0 of the disclosure, and include the crystal structure of both the Cry3A and Cry3B polypeptides disclosed herein. The information provided in Section 9.0 permits the analyses disclosed in each of the methods herein which rely on the 3D crystal structure information for targeting mutagenesis of the polypeptides to particular regions of the primary amino acid sequences of the δ-endotoxins to obtain mutants with increased insecticidal activity or enhanced insecticidal specificity.
A first method for producing a modified B. thuringiensis Cry3Bb δ-endotoxin having improved insecticidal activity or specificity disclosed herein generally involves obtaining a high-resolution 3D crystal structure of the endotoxin, locating in the crystal structure one or more regions of bound water wherein the bound water forms a contiguous hydrated surfaces separated by no more than about 16 Å; increasing the number of water molecules in this surface by increasing the hydrophobicity of one or more amino acids of the protein in the region; and obtaining the modified δ-endotoxin so produced. Exemplary δ-endotoxins include Cry3Bb.11032, Cry3Bb.11227, Cry3Bb.11241, Cry3Bb.11051, Cry3Bb.11242, and Cry3Bb.11098.
A second method for producing a modified B. thuringiensis Cry3Bb δ-endotoxin having improved insecticidal activity comprises identifying a loop region in a δ-endotoxin; modifying one or more amino acids in the loop to increase the hydrophobicity of the amino acids; and obtaining the modified δ-endotoxin so produced. Preferred δ-endotoxin produced by this method include Cry3Bb.11241, Cry3Bb.11242, Cry3Bb.11228, Cry3Bb.11229, Cry3Bb.11230, Cry3Bb.11231, Cry3Bb.11233, Cry3Bb.11236, Cry3Bb.11237, Cry3Bb.11238, and Cry3Bb.11239.
A method for increasing the mobility of channel forming helices of a B. thuringiensis Cry3B δ-endotoxin is also provided by the present invention. The method generally comprises disrupting one or more hydrogen bonds formed between a first amino acid of one or more of the channel forming helices and a second amino acid of the δ-endotoxin. The hydrogen bonds may be formed inter- or intramolecularly, and the disrupting may consist of replacing a first or second amino acid with a third amino acid whose spatial distance is greater than about 3 Å, or whose spatial orientation bond angle is not equal to 180±60 degrees relative to the hydrogen bonding site of the first or second amino acid. δ-endotoxins produced by this method and disclosed herein include Cry3Bb.11222, Cry3Bb.11223, Cry3Bb.11224, Cry3Bb.11225, Cry3Bb.11226, Cry3Bb.11227, Cry3Bb.11231, Cry3Bb.11241, and Cry3Bb.11242, and Cry3Bb.11098.
Also disclosed is a method of increasing the flexibility of a loop region in a channel forming domain of a B. thuringiensis Cry3Bb δ-endotoxin. This method comprises obtaining a crystal structure of a Cry3Bb δ-endotoxin having one or more loop regions; identifying the amino acids comprising the loop region; and altering one or more of the amino acids to reduce steric hindrance in the loop region, wherein the altering increases flexibility of the loop region in the δ-endotoxin. Examples of δ-endotoxins produced using this method include Cry3Bb.11032, Cry3Bb.11051, Cry3Bb.11228, Cry3Bb.11229, Cry3Bb.11230, Cry3Bb.11231, Cry3Bb.11232, Cry3Bb.11233, Cry3Bb.11236, Cry3Bb.11237, Cry3Bb.11238, Cry3Bb.11239, Cry3Bb.11227, Cry3Bb.11234, Cry3Bb.11241, Cry3Bb.11242, Cry3Bb.11036, and Cry3Bb.11098.
Another aspect of the invention is a method for increasing the activity of a δ-endotoxin, comprising reducing or eliminating binding of the δ-endotoxin to a carbohydrate in a target insect gut. The eliminating or reducing may be accomplished by removal of one or more α helices of domain 1 of the δ-endotoxin, for example, by removal of α helices α1, α2a/b, and α3. An exemplary δ-endotoxin produced using the method is Cry3Bb.60.
Alternatively, the reducing or eliminating may be accomplished by replacing one or more amino acids within loop β1,α8, with one or more amino acids having increased hydrophobicity. Such a method gives rise to δ-endotoxins such as Cry3Bb.11228, Cry3Bb.11230, Cry3Bb.11231, Cry3Bb.11237, and Cry3Bb.11098, which are described in detail, herein.
Alternatively, the reducing or eliminating is accomplished by replacing one or more specific amino acids, with any other amino acid. Such replacements are described in Table 2, and in the examples herein. One example is the δ-endotoxin designated herein as Cry3Bb.11221.
A method of identifying a region of a Cry3Bb δ-endotoxin for targeted mutagenesis comprising: obtaining a crystal structure of the δ-endotoxin; identifying from the crystal structure one or more surface-exposed amino acids in the protein; randomly substituting one or more of the surface-exposed amino acids to obtain a plurality of mutated polypeptides, wherein at least 50% of the mutated polypeptides have diminished insecticidal activity; and identifying from the plurality of mutated polypeptides one or more regions of the Cry3Bb δ-endotoxin for targeted mutagenesis. The method may further comprise determining the amino acid sequences of a plurality of mutated polypeptides having diminished activity, and identifying one or more amino acid residues required for insecticidal activity.
In another embodiment, the invention provides a process for producing a Cry3Bb δ-endotoxin having improved insecticidal activity. The process generally involves the steps of obtaining a high-resolution crystal structure of the protein; determining the electrostatic surface distribution of the protein; identifying one or more regions of high electrostatic diversity; modifying the electrostatic diversity of the region by altering one or more amino acids in the region; and obtaining a Cry3Bb δ-endotoxin which has improved insecticidal activity. In one embodiment, the electrostatic diversity may be decreased relative to the electrostatic diversity of a native Cry3Bb δ-endotoxin. Exemplary δ-endotoxins with decreased electrostatic diversity include Cry3Bb.11227, Cry3Bb.11241, and Cry3Bb.11242. Alternatively, the electrostatic diversity may be increased relative to the electrostatic diversity of a native Cry3Bb δ-endotoxin. An exemplary δ-endotoxin with increased electrostatic diversity is Cry3Bb.11234.
Furthermore, the invention also provides a method of producing a Cry3Bb δ-endotoxin having improved insecticidal activity which involves obtaining a high-resolution crystal structure; identifying the presence of one or more metal binding sites in the protein; altering one or more amino acids in the binding site; and obtaining an altered protein, wherein the protein has improved insecticidal activity. The altering may involve the elimination of one or more metal binding sites. Exemplary δ-endotoxin include Cry3Bb.11222, Cry3Bb.11224, Cry3Bb.11225, and Cry3Bb.11226.
A further aspect of the invention involves a method of identifying a B. thuringiensis Cry3Bb δ-endotoxin having improved channel activity. This method in an overall sense involves obtaining a Cry3Bb δ-endotoxin suspected of having improved channel activity; and determining one or more of the following characteristics in the δ-endotoxin, and comparing such characteristics to those obtained for the wild-type unmodified δ-endotoxin: (1) the rate of channel formation, (2) the rate of growth of channel conductance or (3) the duration of open channel state. From this comparison, one may then select a δ-endotoxin which has an increased rate of channel formation compared to the wildtype δ-endotoxin. Examples of Cry3Bb δ-endotoxins prepared by this method include Cry3Bb.60, Cry3Bb.11035, Cry3Bb.11048, Cry3Bb.11032, Cry3Bb.11223, Cry3Bb.11224, Cry3Bb.11226, Cry3Bb.11221, Cry3Bb.11242, Cry3Bb.11230, and Cry3Bb.11098.
Also provided is a method for producing a modified Cry3Bb δ-endotoxin, having improved insecticidal activity which involves altering one or more non-surface amino acids located at or near the point of greatest convergence of two or more loop regions of the Cry3Bb δ-endotoxin, such that the altering decreases the mobility of one or more of the loop regions. The mobility may conveniently be determined by comparing the thermal denaturation of the modified protein to a wild-type Cry3Bb δ-endotoxin. An exemplary crystal protein produced by this method is Cry3Bb.11095.
A further aspect of the invention involves a method for preparing a modified Cry3Bb δ-endotoxin, having improved insecticidal activity comprising modifying one or more amino acids in the loop to increase the hydrophobicity of said amino acids; and altering one or more of said amino acids to reduce steric hindrance in the loop region, wherein the altering increases flexibility of the loop region in the endotoxin. Exemplary Cry3Bb δ-endotoxins produced is selected from the group consisting of Cry3Bb.11057, Cry3Bb.11058, Cry3Bb.11081, Cry3Bb.11082, Cry3Bb.11083, Cry3Bb.11084, Cry3Bb.11231, Cry3Bb.11235, and Cry3Bb.11098.
The invention also provides a method of improving the insecticidal activity of a B. thuringiensis Cry3Bb δ-endotoxin, which generally comprises inserting one or more protease sensitive sites into one or more loop regions of domain 1 of the δ-endotoxin. Preferably, the loop region is α3,4, and an exemplary δ-endotoxin so produced is Cry3Bb.11221.
2.2 Polypeptide Compositions
The crystal proteins so produced by each of the methods described herein also represent important aspects of the invention. Such crystal proteins preferably include a protein or peptide selected from the group consisting of Cry3Bb-60, Cry3Bb.11221, Cry3Bb.11222, Cry3Bb.11223, Cry3Bb.11224, Cry3Bb.11225, Cry3Bb.11226, Cry3Bb.11227, Cry3Bb.11228, Cry3Bb.11229, Cry3Bb.11230, Cry3Bb.11231, Cry3Bb.11232, Cry3Bb.11233, Cry3Bb.11234, Cry3Bb.11235, Cry3Bb.11236, Cry3Bb.11237, Cry3Bb.11238, Cry3Bb.11239, Cry3Bb.11241, Cry3Bb.11242, Cry3Bb.11032, Cry3Bb.11035, Cry3Bb.11036, Cry3Bb.11046, Cry3Bb.11048, Cry3Bb.11051, Cry3Bb.11057, Cry3Bb.11058, Cry3Bb.11081, Cry3Bb.11082, Cry3Bb.11083, Cry3Bb.11084, Cry3Bb.11095, and Cry3Bb.11098.
In preferred embodiments, the protein comprises a contiguous amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6. SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14. SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36. SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102, and SEQ ID NO:108.
Highly preferred are those crystal proteins which are encoded by the nucleic acid sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5. SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13. SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, SEQ ID NO:101; or SEQ ID NO:107, or a nucleic acid sequence which hybridizes to the nucleic acid sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5. SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13. SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, SEQ ID NO:101, or SEQ ID NO:107 under conditions of moderate stringency.
Amino acid, peptide and protein sequences within the scope of the present invention include, and are not limited to the sequences set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22 SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46 SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102, and SEQ ID NO:108, and alterations in the amino acid sequences including alterations, deletions, mutations, and homologs.
Compositions which comprise from about 0.5% to about 99% by weight of the crystal protein, or more preferably from about 5% to about 75%, or from about 25% to about 50% by weight of the crystal protein are provided herein. Such compositions may readily be prepared using techniques of protein production and purification well-known to those of skill, and the methods disclosed herein. Such a process for preparing a Cry3Bb* crystal protein generally involves the steps of culturing a host cell which expresses the Cry3Bb* protein (such as a B. thuringiensis EG11221, EG11222, EG11223, EG11224, EG11225, EG11226, EG11227, EG11228, EG11229, EG11230, EG11231, EG11232, EG11233, EG11234, EG11235, EG11236, EG11237, EG11238, EG11239, EG11241, EG11242, EG11032, EG11035, EG11036, EG11046, EG11048, EG11051, EG11057, EG11058, EG11081, EG11082, EG11083, EG11084, EG11095, or EG11098 cell) under conditions effective to produce the crystal protein, and then obtaining the crystal protein so produced.
The protein may be present within intact cells, and as such, no subsequent protein isolation or purification steps may be required. Alternatively, the cells may be broken, sonicated, lysed, disrupted, or plasmolyzed to free the crystal protein(s) from the remaining cell debris. In such cases, one may desire to isolate, concentrate, or further purify the resulting crystals containing the proteins prior to use, such as, for example, in the formulation of insecticidal compositions. The composition may ultimately be purified to consist almost entirely of the pure protein, or alternatively, be purified or isolated to a degree such that the composition comprises the crystal protein(s) in an amount of from between about 0.5% and about 99% by weight, or in an amount of from between about 5% and about 95% by weight, or in an amount of from between about 15% and about 85% by weight, or in an amount of from between about 25% and about 75% by weight, or in an amount of from between about 40% and about 60% by weight etc.
2.3 Recombinant Vectors Expressing cry3* Genes
One important embodiment of the invention is a recombinant vector which comprises a nucleic acid segment encoding one or more of the novel B. thuringiensis crystal proteins disclosed herein. Such a vector may be transferred to and replicated in a prokaryotic or eukaryotic host, with bacterial cells being particularly preferred as prokaryotic hosts, and plant cells being particularly preferred as eukaryotic hosts.
In preferred embodiments, the recombinant vector comprises a nucleic acid segment encoding the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102, or SEQ ID NO:108. Highly preferred nucleic acid segments are those which have the sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, SEQ ID NO:101, or SEQ ID NO:107.
Another important embodiment of the invention is a transformed host cell which expresses one or more of these recombinant vectors. The host cell may be either prokaryotic or eukaryotic, and particularly preferred host cells are those which express the nucleic acid segment(s) comprising the recombinant vector which encode one or more B. thuringiensis crystal protein comprising modified amino acid sequences in one or more loop regions of domain 1, or between α helix 7 of domain 1 and β strand 1 of domain 2. Bacterial cells are particularly preferred as prokaryotic hosts, and plant cells are particularly preferred as eukaryotic hosts
In an important embodiment, the invention discloses and claims a host cell wherein the modified amino acid sequences comprise one or more loop regions between α helices 1 and 2, α helices 2 and 3, α helices 3 and 4, α helices 4 and 5, α helices 5 and 6 or α helices 6 and 7 of domain 1, or between α helix 7 of domain 1 and β strand 1 of domain 2. A particularly preferred host cell is one that comprises the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102, or SEQ ID NO:108, and more preferably, one that comprises the nucleic acid sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, SEQ ID NO:101, or SEQ ID NO:107.
Bacterial host cells transformed with a nucleic acid segment encoding a modified Cry3Bb crystal protein according to the present invention are disclosed and claimed herein, and in particular, a B. thuringiensis cell having designation EG11221, EG11222, EG11223, EG11224, EG11225, EG11226, EG11227, EG11228, EG11229, EG11230, EG11231, EG11232, EG11233, EG11234, EG11235, EG11236, EG11237, EG11238, EG11239, EG11241, EG11242, EG11032, EG11035, EG11036, EG11046, EG11048, EG11051, EG11057, EG11058, EG11081, EG11082, EG11083, EG11084, EG11095, or EG11098.
In another embodiment, the invention encompasses a method of using a nucleic acid segment of the present invention that encodes a cry3Bb* gene. The method generally comprises the steps of: (a) preparing a recombinant vector in which the cry3Bb* gene is positioned under the control of a promoter; (b) introducing the recombinant vector into a host cell; (c) culturing the host cell under conditions effective to allow expression of the Cry3Bb* crystal protein encoded by said cry3Bb* gene; and (d) obtaining the expressed Cry3Bb* crystal protein or peptide.
A wide variety of ways are available for introducing a B. thuringiensis gene expressing a toxin into the microorganism host under conditions which allow for stable maintenance and expression of the gene. One can provide for DNA constructs which include the transcriptional and translational regulatory signals for expression of the toxin gene, the toxin gene under their regulatory control and a DNA sequence homologous with a sequence in the host organism, whereby integration will occur, and/or a replication system which is functional in the host, whereby integration or stable maintenance will occur.
The transcriptional initiation signals will include a promoter and a transcriptional initiation start site. In some instances, it may be desirable to provide for regulative expression of the toxin, where expression of the toxin will only occur after release into the environment. This can be achieved with operators or a region binding to an activator or enhancers, which are capable of induction upon a change in the physical or chemical environment of the microorganisms. For example, a temperature sensitive regulatory region may be employed, where the organisms may be grown up in the laboratory without expression of a toxin, but upon release into the environment, expression would begin. Other techniques may employ a specific nutrient medium in the laboratory, which inhibits the expression of the toxin, where the nutrient medium in the environment would allow for expression of the toxin. For translational initiation, a ribosomal binding site and an initiation codon will be present.
Various manipulations may be employed for enhancing the expression of the messenger RNA, particularly by using an active promoter, as well as by employing sequences, which enhance the stability of the messenger RNA. The transcriptional and translational termination region will involve stop codon(s), a terminator region, and optionally, a polyadenylation signal. A hydrophobic “leader” sequence may be employed at the amino terminus of the translated polypeptide sequence in order to promote secretion of the protein across the inner membrane.
In the direction of transcription, namely in the 5′ to 3′ direction of the coding or sense sequence, the construct will involve the transcriptional regulatory region, if any, and the promoter, where the regulatory region may be either 5′ or 3′ of the promoter, the ribosomal binding site, the initiation codon, the structural gene having an open reading frame in phase with the initiation codon, the stop codon(s), the polyadenylation signal sequence, if any, and the terminator region. This sequence as a double strand may be used by itself for transformation of a microorganism host, but will usually be included with a DNA sequence involving a marker, where the second DNA sequence may be joined to the toxin expression construct during introduction of the DNA into the host.
By a marker is intended a structural gene which provides for selection of those hosts which have been modified or transformed. The marker will normally provide for selective advantage, for example, providing for biocide resistance, e.g., resistance to antibiotics or heavy metals; complementation, so as to provide prototropy to an auxotrophic host, or the like. Preferably, complementation is employed, so that the modified host may not only be selected, but may also be competitive in the field. One or more markers may be employed in the development of the constructs, as well as for modifying the host. The organisms may be further modified by providing for a competitive advantage against other wild-type microorganisms in the field. For example, genes expressing metal chelating agents, e.g., siderophores, may be introduced into the host along with the structural gene expressing the toxin. In this manner, the enhanced expression of a siderophore may provide for a competitive advantage for the toxin-producing host, so that it may effectively compete with the wild-type microorganisms and stably occupy a niche in the environment.
Where no functional replication system is present, the construct will also include a sequence of at least 50 basepairs (bp), preferably at least about 100 bp, more preferably at least about 1000 bp, and usually not more than about 2000 bp of a sequence homologous with a sequence in the host. In this way, the probability of legitimate recombination is enhanced, so that the gene will be integrated into the host and stably maintained by the host. Desirably, the toxin gene will be in close proximity to the gene providing for complementation as well as the gene providing for the competitive advantage. Therefore, in the event that a toxin gene is lost, the resulting organism will be likely to also lost the complementing gene and/or the gene providing for the competitive advantage, so that it will be unable to compete in the environment with the gene retaining the intact construct.
A large number of transcriptional regulatory regions are available from a wide variety of microorganism hosts, such as bacteria, bacteriophage, cyanobacteria, algac, fungi, and the like. Various transcriptional regulatory regions include the regions associated with the trp gene, lac gene, gal gene, the λL and λR promoters, the tac promoter, the naturally-occurring promoters associated with the δ-endotoxin gene, where functional in the host. See for example, U.S. Pat. Nos. 4,332,898; 4,342,832; and 4,356,270 (each of which is specifically incorporated herein by reference). The termination region may be the termination region normally associated with the transcriptional initiation region or a different transcriptional initiation region, so long as the two regions are compatible and functional in the host.
Where stable episomal maintenance or integration is desired, a plasmid will be employed which has a replication system which is functional in the host. The replication system may be derived from the chromosome, an episomal element normally present in the host or a different host, or a replication system from a virus which is stable in the host. A large number of plasmids are available, such as pBR322, pACYC 84, RSF1010, pR01614, and the like. See for example, Olson et al. (1982); Bagdasarian et al. (1981), Baum et al., 1990, and U.S. Pat. Nos. 4,356,270; 4,362,817; 4,371,625, and 5,441,884, each incorporated specifically herein by reference.
The B. thuringiensis gene can be introduced between the transcriptional and translational initiation region and the transcriptional and translational termination region, so as to be under the regulatory control of the initiation region. This construct will be included in a plasmid, which will include at least one replication system, but may include more than one, where one replication system is employed for cloning during the development of the plasmid and the second replication system is necessary for functioning in the ultimate host. In addition, one or more markers may be present, which have been described previously. Where integration is desired, the plasmid will desirably include a sequence homologous with the host genome.
The transformants can be isolated in accordance with conventional ways, usually employing a selection technique, which allows for selection of the desired organism as against unmodified organisms or transferring organisms, when present. The transformants then can be tested for pesticidal activity. If desired, unwanted or ancillary DNA sequences may be selectively removed from the recombinant bacterium by employing site-specific recombination systems, such as those described in U.S. Pat. No. 5,441,884 (specifically incorporated herein by reference).
2.4 cry3 DNA Segments
A B. thuringiensis cry3* gene encoding a crystal protein having one or more mutations in one or more regions of the peptide represents an important aspect of the invention. Preferably, the cry3* gene encodes an amino acid sequence in which one or more amino acid residues have been changed based on the methods disclosed herein, and particularly those changes which have been made for the purpose of altering the insecticidal activity or specificity of the crystal protein.
In accordance with the present invention, nucleic acid sequences include and are not limited to DNA, including and not limited to cDNA and genomic DNA, genes; RNA, including and not limited to mRNA and tRNA; antisense sequences, nucleosides, and suitable nucleic acid sequences such as those set forth in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, SEQ ID NO:101, or SEQ ID NO:107, and alterations in the nucleic acid sequences including alterations, deletions, mutations, and homologs capable of expressing the B. thuringiensis modified toxins of the present invention.
As such the present invention also concerns DNA segments, that are free from total genomic DNA and that encode the novel synthetically-modified crystal proteins disclosed herein. DNA segments encoding these peptide species may prove to encode proteins, polypeptides, subunits, functional domains, and the like of crystal protein-related or other non-related gene products. In addition these DNA segments may be synthesized entirely in vitro using methods that are well-known to those of skill in the art.
As used herein, the term “DNA segment” refers to a DNA molecule that has been isolated free of total genomic DNA of a particular species. Therefore, a DNA segment encoding a crystal protein or peptide refers to a DNA segment that contains crystal protein coding sequences yet is isolated away from, or purified free from, total genomic DNA of the species from which the DNA segment is obtained, which in the instant case is the genome of the Gram-positive bacterial genus, Bacillus, and in particular, the species of Bacillus known as B. thuringiensis. Included within the term “DNA segment”, are DNA segments and smaller fragments of such segments, and also recombinant vectors, including, for example, plasmids, cosmids, phagemids, phage, viruses, and the like.
Similarly, a DNA segment comprising an isolated or purified crystal protein-encoding gene refers to a DNA segment which may include in addition to peptide encoding sequences, certain other elements such as, regulatory sequences, isolated substantially away from other naturally occurring genes or protein-encoding sequences. In this respect, the term “gene” is used for simplicity to refer to a functional protein-, polypeptide- or peptide-encoding unit. As will be understood by those in the art, this functional term includes both genomic sequences, operon sequences and smaller engineered gene segments that express, or may be adapted to express, proteins, polypeptides or peptides.
“Isolated substantially away from other coding sequences” means that the gene of interest, in this case, a gene encoding a bacterial crystal protein, forms the significant part of the coding region of the DNA segment, and that the DNA segment does not contain large portions of naturally-occurring coding DNA, such as large chromosomal fragments or other functional genes or operon coding regions. Of course, this refers to the DNA segment as originally isolated, and does not exclude genes, recombinant genes, synthetic linkers, or coding regions later added to the segment by the hand of man.
Particularly preferred DNA sequences are those encoding Cry3Bb.60, Cry3Bb.11221, Cry3Bb.11222, Cry3Bb.11223, Cry3Bb.11224, Cry3Bb.11225, Cry3Bb.11226, Cry3Bb.11227, Cry3Bb.11228, Cry3Bb.11229, Cry3Bb.11230, Cry3Bb.11231, Cry3Bb.11232, Cry3Bb.11233, Cry3Bb.11234, Cry3Bb.11235, Cry3Bb.11236, Cry3Bb.11237, Cry3Bb.11238, Cry3Bb.11239, Cry3Bb.11241, Cry3Bb.11242, Cry3Bb.11032, Cry3Bb.11035, Cry3Bb.11036, Cry3Bb.11046, Cry3Bb.11048, Cry3Bb.11051, Cry3Bb.11057, Cry3Bb.11058, Cry3Bb.11081, Cry3Bb.11082, Cry3Bb.11083, Cry3Bb.11084, Cry3Bb.11095 and Cry3Bb.11098 crystal proteins, and in particular cry3Bb* genes such as cry3Bb.60, cry3Bb.11221, cry3Bb.11222, cry3Bb.11223, cry3Bb.11224, cry3Bb.11225, cry3Bb.11226, cry3Bb.11227, cry3Bb.11228, cry3Bb.11229, cry3Bb.11230, cry3Bb.11231, cry3Bb.11232, cry3Bb.11233, cry3Bb.11234, cry3Bb.11235, cry3Bb.11236, cry3Bb.11237, cry3Bb.11238, cry3Bb.11239, cry3Bb.11241, cry3Bb.11242, cry3Bb.11032, cry3Bb.11035, cry3Bb.11036, cry3Bb.11046, cry3Bb.11048, cry3Bb.11051, cry3Bb.11057, cry3Bb.11058, cry3Bb.11081, cry3Bb.11082, cry3Bb.11083, cry3Bb.11084, cry3Bb.11095 and cry3Bb.11098. In particular embodiments, the invention concerns isolated DNA segments and recombinant vectors incorporating DNA sequences that encode a Cry peptide species that includes within its amino acid sequence an amino acid sequence essentially as set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102, or SEQ ID NO:108.
The term “a sequence essentially as set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102, or SEQ ID NO:108” means that the sequence substantially corresponds to a portion of the sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50. SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102, or SEQ ID NO:108, and has relatively few amino acids that are not identical to, or a biologically functional equivalent of, the amino acids of any of these sequences. The term “biologically functional equivalent” is well understood in the art and is further defined in detail herein (e.g., see Illustrative Embodiments).
Accordingly, sequences that have between about 70% and about 75% or between about 75% and about 80%, or more preferably between about 81% and about 90%, or even more preferably between about 91% or 92% or 93% and about 97% or 98% or 99% amino acid sequence identity or functional equivalence to the amino acids of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102 or SEQ ID NO:108 will be sequences that are “essentially as set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102, or SEQ ID NO:108.”
It will also be understood that amino acid and nucleic acid sequences may include additional residues, such as additional N- or C-terminal amino acids or 5′ or 3′ sequences, and yet still be essentially as set forth in one of the sequences disclosed herein, so long as the sequence meets the criteria set forth above, including the maintenance of biological protein activity where protein expression is concerned. The addition of terminal sequences particularly applies to nucleic acid sequences that may, for example, include various non-coding sequences flanking either of the 5′ or 3′ portions of the coding region or may include various internal sequences, i.e., introns, which are known to occur within genes.
The nucleic acid segments of the present invention, regardless of the length of the coding sequence itself, may be combined with other DNA sequences, such as promoters, polyadenylation signals, additional restriction enzyme sites, multiple cloning sites, other coding segments, and the like, such that their overall length may vary considerably. It is therefore contemplated that a nucleic acid fragment of almost any length may be employed, with the total length preferably being limited by the ease of preparation and use in the intended recombinant DNA protocol.
For example, nucleic acid fragments may be prepared that include a short contiguous stretch encoding the peptide sequence disclosed in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102, or SEQ ID NO:108, or that are identical to or complementary to DNA sequences which encode the peptide disclosed in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68. SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102, or SEQ ID NO:108, and particularly the DNA segments disclosed in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, SEQ ID NO:101, or SEQ ID NO:107.
Highly preferred nucleic acid segments of the present invention comprise one or more cry genes of the invention, or a portion of one or more cry genes of the invention. For certain application, relatively small contiguous nucleic acid sequences are preferable, such as those which are about 14 or 15 or 16 or 17 or 18 or 19, or 20, or 30-50, 51-80, 81-100 or so nucleotides in length. Alternatively, in some embodiments, and particularly those involving preparation of recombinant vectors, transformation of suitable host cells, and preparation of transgenic plant cell, longer nucleic acid segments are preferred, particularly those that include the entire coding region of one or more cry genes. As such, the preferred segments may include those that are up to about 20,000 or so nucleotides in length, or alternatively, shorter sequences such as those about 19,000, about 18,000, about 17,000, about 16,000, about 15,000, about 14,000, about 13,000, about 12,000, 11,000, about 10,000, about 9,000, about 8,000, about 7,000, about 6,000, about 5,000, about 4,500, about 4,000, about 3,500, about 3,000, about 2,500, about 2,000, about 1,500, about 1,000, about 500, or about 200 or so base pairs in length. Of course, these numbers are not intended to be exclusionary of all possible intermediate lengths in the range of from about 20,000 to about 15 nucleotides, as all of these intermediate lengths are also contemplated to be useful, and fall within the scope of the present invention. It will be readily understood that “intermediate lengths”, in these contexts, means any length between the quoted ranges, such as 14, 15, 16, 17, 18, 19, 20, etc.; 21, 22, 23, 24, 25, 26, 27, 28, 29, etc.; 30, 31, 32, 33, 34, 35, 36 . . . etc.; 40, 41, 42, 43, 44 . . . etc., 50, 51, 52, 53 . . . etc.; 60, 61, 62, 63 . . . etc., 70, 80, 90, 100, 110, 120, 130 . . . etc.; 200, 210, 220, 230, 240, 250 . . . etc.; including all integers in the entire range from about 14 to about 10,000, including those integers in the ranges 200-500; 500-1,000; 1,000-2,000; 2,000-3,000; 3,000-5,000 and the like.
In a preferred embodiment, the nucleic acid segments comprise a sequence of from about 1800 to about 18,000 base pair in length, and comprise one or more genes which encode a modified Cry3* polypeptide disclosed herein which has increased activity against Coleopteran insect pests.
It will also be understood that this invention is not limited to the particular nucleic acid sequences which encode peptides of the present invention, or which encode the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102, or SEQ ID NO:108, including the DNA sequences which are particularly disclosed in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, SEQ ID NO:101, or SEQ ID NO:107. Recombinant vectors and isolated DNA segments may therefore variously include the peptide-coding regions themselves, coding regions bearing selected alterations or modifications in the basic coding region, or they may encode larger polypeptides that nevertheless include these peptide-coding regions or may encode biologically functional equivalent proteins or peptides that have variant amino acids sequences.
The DNA segments of the present invention encompass biologically-functional, equivalent peptides. Such sequences may arise as a consequence of codon redundancy and functional equivalency that are known to occur naturally within nucleic acid sequences and the proteins thus encoded. Alternatively, functionally-equivalent proteins or peptides may be created via the application of recombinant DNA technology, in which changes in the protein structure may be engineered, based on considerations of the properties of the amino acids being exchanged. Changes designed by man may be introduced through the application of site-directed mutagenesis techniques, e.g., to introduce improvements to the antigenicity of the protein or to test mutants in order to examine activity at the molecular level
If desired, one may also prepare fusion proteins and peptides, e.g., where the peptide-coding regions are aligned within the same expression unit with other proteins or peptides having desired functions, such as for purification or immunodetection purposes (e.g., proteins that may be purified by affinity chromatography and enzyme label coding regions, respectively).
Recombinant vectors form further aspects of the present invention. Particularly useful vectors are contemplated to be those vectors in which the coding portion of the DNA segment, whether encoding a full length protein or smaller peptide, is positioned under the control of a promoter. The promoter may be in the form of the promoter that is naturally associated with a gene encoding peptides of the present invention, as may be obtained by isolating the 5′ non-coding sequences located upstream of the coding segment or exon, for example, using recombinant cloning and/or PCRTM technology, in connection with the compositions disclosed herein.
2.5 Vectors, Host Cells, and Protein Expression
In other embodiments, it is contemplated that certain advantages will be gained by positioning the coding DNA segment under the control of a recombinant, or heterologous, promoter. As used herein, a recombinant or heterologous promoter is intended to refer to a promoter that is not normally associated with a DNA segment encoding a crystal protein or peptide in its natural environment. Such promoters may include promoters normally associated with other genes, and/or promoters isolated from any bacterial, viral, eukaryotic, or plant cell. Naturally, it will be important to employ a promoter that effectively directs the expression of the DNA segment in the cell type, organism, or even animal, chosen for expression. The use of promoter and cell type combinations for protein expression is generally known to those of skill in the art of molecular biology, for example, see Sambrook et al., 1989. The promoters employed may be constitutive, or inducible, and can be used under the appropriate conditions to direct high level expression of the introduced DNA segment, such as is advantageous in the large-scale production of recombinant proteins or peptides. Appropriate promoter systems contemplated for use in high-level expression include, but are not limited to, the Pichia expression vector system (Pharmacia LKB Biotechnology).
In connection with expression embodiments to prepare recombinant proteins and peptides, it is contemplated that longer DNA segments will most often be used, with DNA segments encoding the entire peptide sequence being most preferred. However, it will be appreciated that the use of shorter DNA segments to direct the expression of crystal peptides or epitopic core regions, such as may be used to generate anti-crystal protein antibodies, also falls within the scope of the invention. DNA segments that encode peptide antigens from about 8, 9, 10, or 11 or so amino acids, and up to and including those of about 30, 40, or 50 or so amino acids in length, or more preferably, from about 8 to about 30 amino acids in length, or even more preferably, from about 8 to about 20 amino acids in length are contemplated to be particularly useful. Such peptide epitopes may be amino acid sequences which comprise contiguous amino acid sequence from SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102, or SEQ ID NO:108.
2.6 Transformed Host Cells and Transgenic Plants
In one embodiment, the invention provides a transgenic plant having incorporated into its genome a transgene that encodes a contiguous amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6. SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14. SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, SEQ ID NO:102, and SEQ ID NO:108.
A further aspect of the invention is a transgenic plant having incorporated into its genome a cry3Bb* transgene, provided the transgene comprises a nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5. SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13. SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, SEQ ID NO:101, and SEQ ID NO:107. Also disclosed and claimed are progeny of such a transgenic plant, as well as its seed, progeny from such seeds, and seeds arising from the second and subsequent generation plants derived from such a transgenic plant.
The invention also discloses and claims host cells, both native, and genetically engineered, which express the novel cry3Bb* genes to produce Cry3Bb* polypeptides. Preferred examples of bacterial host cells include B. thuringiensis EG11221, EG11222, EG11223, EG11224, EG11225, EG11226, EG11227, EG11228, EG11229, EG11230, EG11231, EG11232, EG11233, EG11234, EG11235, EG11236, EG11237, EG11238, EG11239, EG11241, EG11242, EG11032, EG11035, EG11036, EG11046, EG11048, EG11051, EG11057, EG11058, EG11081, EG11082, EG11083, EG11084, EG11095, and EG11098.
Methods of using such cells to produce Cry3* crystal proteins are also disclosed. Such methods generally involve culturing the host cell (such as B. thuringiensis EG11221, EG11222, EG11223, EG11224, EG11225, EG11226, EG11227, EG11228, EG11229, EG11230, EG11231, EG11232, EG11233, EG11234, EG11235, EG11236, EG11237. EG11238, EG11239, EG11241, EG11242, EG11032, EG11035, EG11036, EG11046, EG11048, EG11051, EG11057, EG11058, EG11081, EG11082, EG11083, EG11084, or EG11095, or EG11098) under conditions effective to produce a Cry3* crystal protein, and obtaining the Cry3* crystal protein from said cell.
In yet another aspect, the present invention provides methods for producing a transgenic plant which expresses a nucleic acid segment encoding the novel recombinant crystal proteins of the present invention. The process of producing transgenic plants is well-known in the art. In general, the method comprises transforming a suitable host cell with one or more DNA segments which contain one or more promoters operatively linked to a coding region that encodes one or more of the disclosed B. thuringiensis crystal proteins. Such a coding region is generally operatively linked to a transcription-terminating region, whereby the promoter is capable of driving the transcription of the coding region in the cell, and hence providing the cell the ability to produce the recombinant protein in vivo. Alternatively, in instances where it is desirable to control, regulate, or decrease the amount of a particular recombinant crystal protein expressed in a particular transgenic cell, the invention also provides for the expression of crystal protein antisense mRNA. The use of antisense mRNA as a means of controlling or decreasing the amount of a given protein of interest in a cell is well-known in the art.
Another aspect of the invention comprises a transgenic plant which express a gene or gene segment encoding one or more of the novel polypeptide compositions disclosed herein. As used herein, the term “transgenic plant” is intended to refer to a plant that has incorporated DNA sequences, including but not limited to genes which are perhaps not normally present, DNA sequences not normally transcribed into RNA or translated into a protein (“expressed”), or any other genes or DNA sequences which one desires to introduce into the non-transformed plant, such as genes which may normally be present in the non-transformed plant but which one desires to either genetically engineer or to have altered expression.
It is contemplated that in some instances the genome of a transgenic plant of the present invention will have been augmented through the stable introduction of one or more Cry3Bb*-encoding transgenes, either native, synthetically modified, or mutated. In some instances, more than one transgene will be incorporated into the genome of the transformed host plant cell. Such is the case when more than one crystal protein-encoding DNA segment is incorporated into the genome of such a plant. In certain situations, it may be desirable to have one, two, three, four, or even more B. thuringiensis crystal proteins (either native or recombinantly-engineered) incorporated and stably expressed in the transformed transgenic plant.
A preferred gene which may be introduced includes, for example, a crystal protein-encoding a DNA sequence from bacterial origin, and particularly one or more of those described herein which are obtained from Bacillus spp. Highly preferred nucleic acid sequences are those obtained from B. thuringiensis, or any of those sequences which have been genetically engineered to decrease or increase the insecticidal activity of the crystal protein in such a transformed host cell.
Means for transforming a plant cell and the preparation of a transgenic cell line are well-known in the art, and are discussed herein. Vectors, plasmids, cosmids, YACs (yeast artificial chromosomes) and DNA segments for use in transforming such cells will, of course, generally comprise either the operons, genes, or gene-derived sequences of the present invention, either native, or synthetically-derived, and particularly those encoding the disclosed crystal proteins. These DNA constructs can further include structures such as promoters, enhancers, polylinkers, or even gene sequences which have positively- or negatively-regulating activity upon the particular genes of interest as desired. The DNA segment or gene may encode either a native or modified crystal protein, which will be expressed in the resultant recombinant cells, and/or which will impart an improved phenotype to the regenerated plant
Such transgenic plants may be desirable for increasing the insecticidal resistance of a monocotyledonous or dicotyledonous plant, by incorporating into such a plant, a transgenic DNA segment encoding a Cry3Bb* crystal protein which is toxic to coleopteran insects. Particularly preferred plants include grains such as corn, wheat, rye, rice, barley, and oats; legumes such as soybeans; tubers such as potatoes; fiber crops such as flax and cotton; turf and pasture grasses; ornamental plants; shrubs; trees; vegetables, berries, citrus, fruits, cacti, succulents, and other commercially-important crops including garden and houseplants.
In a related aspect, the present invention also encompasses a seed produced by the transformed plant, a progeny from such seed, and a seed produced by the progeny of the original transgenic plant, produced in accordance with the above process. Such progeny and seeds will have one or more crystal protein transgene(s) stably incorporated into its genome, and such progeny plants will inherit the traits afforded by the introduction of a stable transgene in Mendelian fashion. All such transgenic plants having incorporated into their genome transgenic DNA segments encoding one or more Cry3Bb* crystal proteins or polypeptides are aspects of this invention. Particularly preferred transgenes for the practice of the invention include nucleic acid segments comprising one or more cry3Bb* gene(s).
2.7 Biological Functional Equivalents
Modification and changes may be made in the structure of the peptides of the present invention and DNA segments which encode them and still obtain a functional molecule that encodes a protein or peptide with desirable characteristics. The following is a discussion based upon changing the amino acids of a protein to create an equivalent, or even an improved, second-generation molecule. In particular embodiments of the invention, mutated crystal proteins are contemplated to be useful for increasing the insecticidal activity of the protein, and consequently increasing the insecticidal activity and/or expression of the recombinant transgene in a plant cell. The amino acid changes may be achieved by changing the codons of the DNA sequence, according to the codons given in Table 4.








TABLE 4





Amino Acids
Codons


















Alanine
Ala
A
GCA GCC GCG GCU


 


Cysteine
Cys
C
UGC UGU


 


Aspartic Acid
Asp
D
GAC GAU


 


Glutamic Acid
Glu
E
GAA GAG


 


Phenylalanine
Phe
F
UUC UUU


 


Glycine
Gly
G
GGA GGC GGG GGU


 


Histidine
His
H
CAC CAU


 


Isoleucine
Ile
I
AUA AUC AUU


 


Lysine
Lys
K
AAA AAG


 


Leucine
Leu
L
UUA UUG CUA CUC CUC CUU


 


Methionine
Met
M
AUG


 


Asparagine
Asn
N
AAC AAU


 


Proline
Pro
P
CCA CCC CCG CCU


 


Glutamine
Gln
Q
CAA CAG


 


Arginine
Arg
R
AGA AGG CGA CGC CGG CGU


 


Serine
Ser
S
AGC AGU UCA UCC UCG UCU


 


Threonine
Thr
T
ACA ACC ACG ACU


 


Valine
Val
V
GUA GUC GUG GUU


 


Tryptophan
Trp
W
UGG


 


Tyrosine
Tyr
Y
UAC UAU









For example, certain amino acids may be substituted for other amino acids in a protein structure without appreciable loss of interactive binding capacity with structures such as, for example, antigen-binding regions of antibodies or binding sites on substrate molecules. Since it is the interactive capacity and nature of a protein that defines that protein's biological functional activity, certain amino acid sequence substitutions can be made in a protein sequence, and, of course, its underlying DNA coding sequence, and nevertheless obtain a protein with like properties. It is thus contemplated by the inventors that various changes may be made in the peptide sequences of the disclosed compositions, or corresponding DNA sequences which encode said peptides without appreciable loss of their biological utility or activity.
In making such changes, the hydropathic index of amino acids may be considered. The importance of the hydropathic amino acid index in conferring interactive biologic function on a protein is generally understood in the art (Kyte and Doolittle, 1982, incorporate herein by reference). It is accepted that the relative hydropathic character of the amino acid contributes to the secondary structure of the resultant protein, which in turn defines the interaction of the protein with other molecules, for example, enzymes, substrates, receptors, DNA, antibodies, antigens, and the like.
Each amino acid has been assigned a hydropathic index on the basis of their hydrophobicity and charge characteristics (Kyte and Doolittle, 1982), these are: isoleucine (+4.5); valine (+4.2); leucine (+3.8); phenylalanine (+2.8); cysteine/cystine (+2.5); methionine (+1.9); alanine (+1.8); glycine (−0.4); threonine (−0.7); serine (−0.8); tryptophan (−0.9); tyrosine (−1.3); proline (−1.6); histidine (−3.2); glutamate (−3.5); glutamine (−3.5); aspartate (−3.5); asparagine (−3.5); lysine (−3.9); and arginine (−4.5).
It is known in the art that certain amino acids may be substituted by other amino acids having a similar hydropathic index or score and still result in a protein with similar biological activity, i.e., still obtain a biological functionally equivalent protein. In making such changes, the substitution of amino acids whose hydropathic indices are within ±2 is preferred, those which are within ±1 are particularly preferred, and those within ±0.5 are even more particularly preferred.
It is also understood in the art that the substitution of like amino acids can be made effectively on the basis of hydrophilicity. U.S. Pat. No. 4,554,101, specifically incorporated herein by reference, states that the greatest local average hydrophilicity of a protein, as governed by the hydrophilicity of its adjacent amino acids, correlates with a biological property of the protein.
As detailed in U.S. Pat. No. 4,554,101, the following hydrophilicity values have been assigned to amino acid residues: arginine (+3.0); lysine (+3.0); aspartate (+3.0±1); glutamate (+3.0±1); serine (+0.3); asparagine (+0.2); glutamine (+0.2); glycine (0); threonine (−0.4); proline (−0.5±1); alanine (−0.5); histidine (−0.5); cysteine (−1.0); methionine (−1.3); valine (−1.5); leucine (−1.8); isoleucine (−1.8); tyrosine (−2.3); phenylalanine (−2.5); tryptophan (−3.4).
It is understood that an amino acid can be substituted for another having a similar hydrophilicity value and still obtain a biologically equivalent, and in particular, an immunologically equivalent protein. In such changes, the substitution of amino acids whose hydrophilicity values are within ±2 is preferred, those which are within ±1 are particularly preferred, and those within ±0.5 are even more particularly preferred.
As outlined above, amino acid substitutions are generally therefore based on the relative similarity of the amino acid side-chain substituents, for example, their hydrophobicity, hydrophilicity, charge, size, and the like. Exemplary substitutions which take various of the foregoing characteristics into consideration are well known to those of skill in the art and include: arginine and lysine; glutamate and aspartate; serine and threonine; glutamine and asparagine; and valine, leucine and isoleucine.



3.0 BRIEF DESCRIPTION OF THE DRAWINGS
The drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein.
FIG. 1. Schematic representation of the monomeric structure of Cry3Bb.
FIG. 2. Stereoscopic view of the monomeric structure of Cry3Bb with associated water molecules (represented by dots).
FIG. 3A. Schematic representation of domain 1 of Cry3Bb
FIG. 3B. Diagram of the positions of the 7 helices that comprise domain 1.
FIG. 4. Domain 1 of Cry3Bb is organized into seven α helices illustrated in FIG. 3A (schematic representation) and FIG. 3B (schematic diagram). The α helices and amino acids residues are shown.
FIG. 5A. Schematic representation of domain 2 of Cry3Bb.
FIG. 5B. Diagram of the positions of the 11 β strands that compose the 3 β sheets of domain 2.
FIG. 6. Domain 2 of Cry3Bb is a collection of three anti-parallel β sheets illustrated in FIG. 5. The amino acids that define these sheets is listed below (α8, amino aids 322-328, also is included in domain 2):
FIG. 7A. Schematic representation of domain 3 of Cry3Bb.
FIG. 7B. Diagram of the positions of the β strands that comprise domain 3.
FIG. 8. Domain 3 (FIG. 7) is a loosely organized collection of β strands and loops; no β sheets are present. The β stands contain the amino acids limited below:
FIG. 9A. A “side” view of the dimeric structure of Cry3Bb. The helical bundles of domains 1 can be seem in the middle of the molecule.
FIG. 9B. A “top” view of the dimeric structure of Cry3Bb. The helical bundles of domains 1 can be seem in the middle of the molecule.
FIG. 10. A graphic representation of the growth in conductance with time of channels formed by Cry3A and Cry3Bb in planar lipid bilayers. Cry3A forms channels with higher conductances much more rapidly than Cry3Bb.
FIG. 11. A map of pEG1701 which contains the Cry3Bb gene with the cry1F terminator.
FIG. 12. The results of replicated 1-dose assays against SCRW larvae of Cry3Bb proteins altered in the 1B2,3 region.
FIG. 13. The results of replicated, 1-dose assays against SCRW larvae of Cry3Bb proteins altered in the 1B6, 7 region.
FIG. 14. The results of replicated, 1-dose screens against SCRW larvae of Cry3Bb proteins altered in the 1B10,11 region.
FIG. 15. Single channel recordings of channels formed by Cry3Bb.11230 and WT Cry3Bb in planar lipid bilayers. Cry3Bb.11230 forms channels with well resolved open and closed states while Cry3Bb rarely does.
FIG. 16. Single channel recordings of channels formed by Cry3Bb and Cry3Bb.60, a truncated form of Cry3Bb. Cry3Bb.60 forms channels more quickly than Cry3Bb and, unlike Cry3Bb, produces channels with well resolved open and closed states.
FIG. 17A. Sequence alignment of the amino acid sequence of Cry3C (SEQ ID NO:109), Cry3Bb2 (SEQ ID NO:110), Cry3Bb (SEQ ID NO:111), Cry3Ba (SEQ ID NO:112) and Cry3A (SEQ ID NO:113).
FIG. 17B. Shown is a continuation of the alignment shown in FIG. 17A.
FIG. 17C. Shown is a continuation of the alignment shown in FIGS. 17A and 17B.



4.0 DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
The invention defines new B. thuringiensis (Bt) insecticidal δ-endotoxin proteins and the biochemical and biophysical strategies used to design the new proteins. Delta-endotoxins are a class of insecticdal proteins produced by B. thuringiensis that form cation-selective channels in planar lipid bilayers (English and Slatin, 1992). The new δ-endotoxins are based on the parent structure of the coleopteran-active, δ-endotoxin Cry3Bb. Like other members of the coleopteran-active class of δ-endotoxins, including Cry3A and Cry3B, Cry3Bb exhibits excellent insecticidal activity against the Colorado Potato Beetle (Leptinotarsa decemlineata). However, unlike Cry3A and Cry3B, Cry3Bb is also active against the southern corn rootworm or SCRW (Diabrotica undecimpuncrata howardi Barber) and the western corn rootworm or WCRW (Diabrotica virgifera virgifera LeConte). The new insecticidal proteins described herein were specifically designed to improve the biological activity of the parent Cry3Bb protein. In addition, the design strategies themselves are novel inventions capable of being applied to and improving B. thuringiensis δ-endotoxins in general. B. thuringiensis δ-endotoxins are also members of a larger class of bacterial toxins that form ion channels (see English and Slatin 1992, for a review). The inventors, therefore, believe that these design strategies can also be applied to any biologically active, channel-forming protein to improve its biological properties.
The designed Cry3Bb proteins were engineered using one or more of the following strategies including (1) identification and alteration of protease-sensitive sites and proteolytic processing; (2) analysis and manipulation of bound water; (3) manipulation of hydrogen bonds around mobile regions; (4) loop analysis and loop redesign around flexible helices; (5) loop design around β strands and β sheets; (6) identification and redesign of complex electrostatic surfaces; (7) identification and removal of metal binding sites; (8) alteration of quaternary structure; (9) identification and design of structural residues; and (10) combinations of any and all sites defined by strategies 1-9. These design strategies permit the identification and redesign of specific sites on Cry3Bb, ultimately creating new proteins with improved insecticidal activities. These new proteins are designated Cry3Bb designed proteins and are named Cry3Bb followed by a period and a suffix (e.g., Cry3Bb.60, Cry3Bb.11231). The new proteins are listed in Table 2 along with the specific sites on the molecule that were modified, the amino-acid sequence changes at those sites that improve biological activity, the improved insecticidal activities and the design method used to identify that specific site.
4.1 Some Advantages of the Invention
Mutagenesis studies with cry genes have failed to identify a significant number of mutant crystal proteins which have improved broad-spectrum insecticidal activity, that is, with improved toxicity towards a range of insect pest species. Since agricultural crops are typically threatened by more than one insect pest species at any given time, desirable mutant crystal proteins are preferably those that exhibit improvements in toxicity towards multiple insect pest species. Previous failures to identify such mutants may be attributed to the choice of sites targeted for mutagenesis. For example, with respect to the related protein, Cry1C, sites within domain 2 and domain 3 have been the principal targets of mutagenesis efforts, primarily because these domains are believed to be important for receptor binding and in determining insecticidal specificity (Aronson et al., 1995; Chen et al. 1993; de Maagd et al., 1996; Lee et al., 1992; Lee et al., 1995; Lu et al., 1994; Smedley and Ellar, 1996; Smith and Ellar, 1994; Rajamohan et al., 1995; Rajamohan et al., 1996)
In contrast, the present inventors reasoned that the toxicity of Cry3 proteins, and specifically the toxicity of the Cry3Bb protein, may be improved against a broader array of target pests by targeting regions involved in ion channel function rather than regions of the molecule directly involved in receptor interactions, namely domains 2 and 3. Accordingly, the inventors opted to target regions within domain 1 of Cry3Bb for mutagenesis for the purpose of isolating Cry3Bb mutants with improved broad spectrum toxicity. Indeed, in the pre-sent invention, Cry3Bb mutants are described that show improved toxicity towards several coleopteran pests.
At least one, and probably more than one, α helix of domain 1 is involved in the formation of ion channels and pores within the insect midgut epithelium (Gazit and Shai, 1993; Gazit and Shai, 1995). Rather than target for mutagenesis the sequences encoding the α helices of domain 1 as others have (Wu and Aronson, 1992; Aronson et al., 1995; Chen et al., 1995), the present inventors opted to target exclusively sequences encoding amino acid residues adjacent to or lying within the predicted loop regions of Cry3Bb that separate these α helices. Amino acid residues within these loop regions or amino acid residues capping the end of an α helix and lying adjacent to these loop regions may affect the spatial relationships among these α helices. Consequently, the substitution of these amino acid residues may result in subtle changes in tertiary structure, or even quaternary structure, that positively impact the function of the ion channel. Amino acid residues in the loop regions of domain I are exposed to the solvent and thus are available for various molecular interactions. Altering these amino acids could result in greater stability of the protein by eliminating or occluding protease-sensitive sites. Amino acid substitutions that change the surface charge of domain 1 could alter ion channel efficiency or alter interactions with the brush border membrane or with other portions of the toxin molecule, allowing binding or insertion to be more effective.
According to this invention, base substitutions are made in the underlying cry3Bb nucleic acid residues in order to change particular codons of the corresponding polypeptides, and particularly, in those loop regions between α-helices. The insecticidal activity of a crystal protein ultimately dictates the level of crystal protein required for effective insect control. The potency of an insecticidal protein should be maximized as much as possible in order to provide for its economic and efficient utilization in the field. The increased potency of an insecticidal protein in a bioinsecticide formulation would be expected to improve the field performance of the bioinsecticide product. Alternatively, increased potency of an insecticidal protein in a bioinsecticide formulation may promote use of reduced amounts of bioinsecticide per unit area of treated crop, thereby allowing for more cost-effective use of the bioinsecticide product. When expressed in planta, the production of crystal proteins with improved insecticidal activity can be expected to improve plant resistance to susceptible insect pests.
4.2 Methods for Culturing B. Thuringiensis to Produce Crystal Proteins
The B. thuringiensis strains described herein may be cultured using standard known media and fermentation techniques. Upon completion of the fermentation cycle, the bacteria may be harvested by first separating the B. thuringiensis spores and crystals from the fermentation broth by means well known in the art. The recovered B. thuringiensis spores and crystals can be formulated into a wettable powder, a liquid concentrate, granules or other formulations by the addition of surfactants, dispersants, inert carriers and other components to facilitate handling and application for particular target pests. The formulation and application procedures are all well known in the art.
4.3 Recombinant Host Cells for Expression of Cry* Genes
The nucleotide sequences of the subject invention can be introduced into a wide variety of microbial hosts. Expression of the toxin gene results, directly or indirectly, in the intracellular production and maintenance of the pesticide. With suitable hosts, e.g., Pseudomonas, the microbes can be applied to the sites of coleopteran insects where they will proliferate and be ingested by the insects. The result is a control of the unwanted insects. Alternatively, the microbe hosting the toxin gene can be treated under conditions that prolong the activity of the toxin produced in the cell. The treated cell then can be applied to the environment of target pest(s). The resulting product retains the toxicity of the B. thuringiensis toxin.
Suitable host cells, where the pesticide-containing cells will be treated to prolong the activity of the toxin in the cell when the then treated cell is applied to the environment of target pest(s), may include either prokaryotes or eukaryotes, normally being limited to those cells which do not produce substances toxic to higher organisms, such as mammals. However, organisms which produce substances toxic to higher organisms could be used, where the toxin is unstable or the level of application sufficiently low as to avoid any possibility or toxicity to a mammalian host. As hosts, of particular interest will be the prokaryotes and the lower eukaryotes, such as fungi. Illustrative prokaryotes, both Gram-negative and Gram-positive, include Enterobacteriaceae, such as Escherichia, Erwinia, Shigella, Salmonella, and Proteus; Bacillaceae; Rhizobiceae, such as Rhizobium; Spirillaceae, such as photobacterium, Zymomonas, Serratia, Aeromonas, Vibrio, Desulfovibrio, Spirillum; Lactobacillaceae; Pseudomonadaceae, such as Pseudomonas and Acetobacter; Azotobacteraceae, Actinomycetales, and Nitrobacteraceae. Among eukaryotes are fungi, such as Phycomycetes and Ascomycetes, which includes yeast, such as Saccharomyces and Schizosaccharomyces; and Basidiomycetes yeast, such as Rhodotorula, Aureobasidium, Sporobolomyces, and the like.
Characteristics of particular interest in selecting a host cell for purposes of production include ease of introducing the B. thuringiensis gene into the host, availability of expression systems, efficiency of expression, stability of the pesticide in the host, and the presence of auxiliary genetic capabilities. Characteristics of interest for use as a pesticide microcapsule include protective qualities for the pesticide, such as thick cell walls, pigmentation, and intracellular packaging or formation of inclusion bodies; leaf affinity; lack of mammalian toxicity; attractiveness to pests for ingestion; ease of killing and fixing without damage to the toxin; and the like. Other considerations include ease of formulation and handling, economics, storage stability, and the like.
Host organisms of particular interest include yeast, such as Rhodotorula sp., Aureobasidium sp., Saccharomyces sp., and Sporobolomyces sp.; phylloplane organisms such as Pseudomonas sp., Erwinia sp. and Flavobacterium sp.; or such other organisms as Escherichia, Lactobacillus sp., Bacillus sp., Streptomyces sp., and the like. Specific organisms include Pseudomonas aeruginosa, Pseudomonas fluorescens, Saccharomyces cerevisiae, B. thuringiensis, Escherichia coli, B. subtilis, B. megaterium, B. cereus, Streptomyces lividans and the like.
Treatment of the microbial cell, e.g., a microbe containing the B. thuringiensis toxin gene, can be by chemical or physical means, or by a combination of chemical and/or physical means, so long as the technique does not deleteriously affect the properties of the toxin, nor diminish the cellular capability in protecting the toxin. Examples of chemical reagents are halogenating agents, particularly halogens of atomic no. 17-80. More particularly, iodine can be used under mild conditions and for sufficient time to achieve the desired results. Other suitable techniques include treatment with aldehydes, such as formaldehyde and glutaraldehye; anti-infectives, such as zephiran chloride and cetylpyridinium chloride; alcohols, such as isopropyl and ethanol; various histologic fixatives, such as Lugol's iodine, Bouin's fixative, and Helly's fixatives, (see e.g., Humason, 1967); or a combination of physical (heat) and chemical agents that preserve and prolong the activity of the toxin produced in the cell when the cell is administered to the host animal. Examples of physical means are short wavelength radiation such as γ-radiation and X-radiation, freezing, UV irradiation, lyophilization, and the like. The cells employed will usually be intact and be substantially in the proliferative form when treated, rather than in a spore form, although in some instances spores may be employed.
Where the B. thuringiensis toxin gene is introduced via a suitable vector into a microbial host, and said host is applied to the environment in a living state, it is essential that certain host microbes be used. Microorganism hosts are selected which are known to occupy the “phytosphere” (phylloplane, phyllosphere, rhizosphere, and/or rhizoplane) of one or more crops of interest. These microorganisms are selected so as to be capable of successfully competing in the particular environment (crop and other insect habitats) with the wild-type microorganisms, provide for stable maintenance and expression of the gene expressing the polypeptide pesticide, and, desirably, provide for improved protection of the pesticide from environmental degradation and inactivation.
A large number of microorganisms are known to inhabit the phylloplane (the surface of the plant leaves) and/or the rhizosphere (the soil surrounding plant roots) of a wide variety of important crops. These microorganisms include bacteria, algae, and fungi. Of particular interest are microorganisms, such as bacteria, e.g., genera Bacillus (including the species and subspecies B. thuringiensis kurstaki HD-1, B. thuringiensis kurstaki HD-73, B. thuringiensis sotto, B. thuringiensis berliner, B. thuringiensis thuringiensis, B. thuringiensis totworthi, B. thuringiensis dendrolimus, B. thuringiensis alesti, B. thuringiensis galleriae, B. thuringiensis aizawai, B. thuringiensis subtoxicus, B. thuringiensis entomocidus, B. thuringiensis tenebrionis and B. thuringiensis son diego); Pseudomonas, Erwinia, Serratia, Klebsiella, Zanthomonas, Streptomyces, Rhizobium, Rhodopseudomonas, Methylophilius, Agrobacterium, Acetobacter, Lactobacillus, Arthrobacter, Azotobacter, Leuconostoc, and Alcaligenes; fungi, particularly yeast, e.g., genera Saccharomyces, Cryptococcus, Kluyveromyces, Sporobolomyces, Rhodotorula, and Aureobasidium. Of particular interest are such phytosphere bacterial species as Pseudomonas syringae, Pseudomonas fluorescens, Serratia marcescens, Acetobacter xylinum, Agrobacterium tumefaciens, Rhodobacter sphaeroides, Xanthomonas campestris, Rhizobium melioti, Alcaligenes eutrophus, and Azotobacter vinlandii; and phytosphere yeast species such as Rhodotorula rubra, R. glutinis, R. marina, R. aurantiaca, Cryptococcus albidus, C. diffluens, C. laurentii, Saccharomyces rosei, S. pretoriensis, S. cerevisiae, Sporobolomyces roseus, S. odorus, Kluyveromyces veronae, and Aureobasidium pollulans. 
4.4 Definitions
In accordance with the present invention, nucleic acid sequences include and are not limited to DNA (including and not limited to genomic or extragenomic DNA), genes, RNA (including and not limited to mRNA and tRNA), nucleosides, and suitable nucleic acid segments either obtained from native sources, chemically synthesized, modified, or otherwise prepared by the hand of man. The following words and phrases have the meanings set forth below.
A, an: In accordance with long standing patent law convention, the words “a” and “an” when used in this application, including the claims, denotes “one or more”.
Broad-spectrum: Refers to a wide range of insect species.
Broad-spectrum activity: The toxicity towards a wide range of insect species.
Expression: The combination of intracellular processes, including transcription and translation undergone by a coding DNA molecule such as a structural gene to produce a polypeptide.
Insecticidal activity: The toxicity towards insects.
Insecticidal specificity: The toxicity exhibited by a crystal protein or proteins, microbe or plant, towards multiple insect species.
Intraorder specificity: The toxicity of a particular crystal protein towards insect species within an Order of insects (e.g., Order Coleoptera).
Interorder specificity: The toxicity of a particular crystal protein towards insect species of different Orders (e.g., Orders Coleoptera and Diptera).
LC50: The lethal concentration of crystal protein that causes 50% mortality of the insects treated.
LC95: The lethal concentration of crystal protein that causes 95% mortality of the insects treated.
Promoter: A recognition site on a DNA sequence or group of DNA sequences that provide an expression control element for a structural gene and to which RNA polymerase specifically binds and initiates RNA synthesis (transcription) of that gene.
Regeneration: The process of growing a plant from a plant cell (e.g., plant protoplast or explant).
Structural gene: A gene that is expressed to produce a polypeptide.
Transformation: A process of introducing an exogenous DNA sequence (e.g., a vector, a recombinant DNA molecule) into a cell or protoplast in which that exogenous DNA is incorporated into a chromosome or is capable of autonomous replication.
Transformed cell: A cell whose DNA has been altered by the introduction of an exogenous DNA molecule into that cell.
Transgenic cell: Any cell derived or regenerated from a transformed cell or derived from a transgenic cell. Exemplary transgenic cells include plant calli derived from a transformed plant cell and particular cells such as leaf, root, stem, e.g., somatic cells, or reproductive (germ) cells obtained from a transgenic plant.
Transgenic plant: A plant or progeny thereof derived from a transformed plant cell or protoplast, wherein the plant DNA contains an introduced exogenous DNA molecule not originally present in a native, non-transgenic plant of the same strain. The terms “transgenic plant” and “transformed plant” have sometimes been used in the art as synonymous terms to define a plant whose DNA contains an exogenous DNA molecule. However, it is thought more scientifically correct to refer to a regenerated plant or callus obtained from a transformed plant cell or protoplast as being a transgenic plant, and that usage will be followed herein.
Vector: A DNA molecule capable of replication in a host cell and/or to which another DNA segment can be operatively linked so as to bring about replication of the attached segment. A plasmid is an exemplary vector.
As used herein, the designations “CryII” and “Cry3” are synonymous, as are the designations “CryIIIB2” and “Cry3Bb.” Likewise, the inventors have utilized the generic term Cry3Bb* to denote any and all Cry3Bb variants which comprise amino acid sequences modified in the protein. Similarly, cry3Bb* is meant to denote any and all nucleic acid segments and/or genes which encode a Cry3Bb* protein, etc.
4.5 Preparation of cry3* Polynucleotides
Once the structure of the desired peptide to be mutagenized has been analyzed using one or more of the design strategies disclosed herein, it will be desirable to introduce one or more mutations into either the protein or, alternatively, into the DNA sequence encoding the protein for the purpose of producing a mutated protein with altered bioinsecticidal properties.
To that end, the present invention encompasses both site-specific mutagenesis methods and random mutagenesis of a nucleic acid segment encoding a crystal protein in the manner described herein. In particular, methods are disclosed for the mutagenesis of nucleic acid segments encoding the amino acid sequences using one or more of the design strategies described herein. Using the assay methods described herein, one may then identify mutants arising from these procedures which have improved insecticidal properties or altered specificity, either intraorder or interorder.
The means for mutagenizing a DNA segment encoding a crystal protein are well-known to those of skill in the art. Modifications may be made by random, or site-specific mutagenesis procedures. The nucleic acid may be modified by altering its structure through the addition or deletion of one or more nucleotides from the sequence.
Mutagenesis may be performed in accordance with any of the techniques known in the art such as and not limited to synthesizing an oligonucleotide having one or more mutations within the sequence of a particular crystal protein. A “suitable host” is any host which will express Cry3Bb, such as and not limited to B. thuringiensis and E. coli. Screening for insecticidal activity, in the case of Cry3Bb includes and is not limited to coleopteran-toxic activity which may be screened for by techniques known in the art.
In particular, site-specific mutagenesis is a technique useful in the preparation of individual peptides, or biologically functional equivalent proteins or peptides, through specific mutagenesis of the underlying DNA. The technique further provides a ready ability to prepare and test sequence variants, for example, incorporating one or more of the foregoing considerations, by introducing one or more nucleotide sequence changes into the DNA. Site-specific mutagenesis allows the production of mutants through the use of specific oligonucleotide sequences which encode the DNA sequence of the desired mutation, as well as a sufficient number of adjacent nucleotides, to provide a primer sequence of sufficient size and sequence complexity to form a stable duplex on both sides of the deletion junction being traversed. Typically, a primer of about 17 to about 75 nucleotides or more in length is preferred, with about 10 to about 25 or more residues on both sides of the junction of the sequence being altered.
In general, the technique of site-specific mutagenesis is well known in the art, as exemplified by various publications. As will be appreciated, the technique typically employs a phage vector which exists in both a single stranded and double stranded form. Typical vectors useful in site-directed mutagenesis include vectors such as the M13 phage. These phage are readily commercially available and their use is generally well known to those skilled in the art. Double stranded plasmids are also routinely employed in site directed mutagenesis which eliminates the step of transferring the gene of interest from a plasmid to a phage.
In general, site-directed mutagenesis in accordance herewith is performed by first obtaining a single-stranded vector or melting apart of two strands of a double stranded vector which includes within its sequence a DNA sequence which encodes the desired peptide. An oligonucleotide primer bearing the desired mutated sequence is prepared, generally synthetically. This primer is then annealed with the single-stranded vector, and subjected to DNA polymerizing enzymes such as E. coli polymerase I Klenow fragment, in order to complete the synthesis of the mutation-bearing strand. Thus, a heteroduplex is formed wherein one strand encodes the original non-mutated sequence and the second strand bears the desired mutation. This heteroduplex vector is then used to transform or transfect appropriate cells, such as E coli cells, and clones are selected which include recombinant vectors bearing the mutated sequence arrangement. A genetic selection scheme was devised by Kunkel et al. (1987) to enrich for clones incorporating the mutagenic oligonucleotide. Alternatively, the use of PCRTM with commercially available thermostable enzymes such as Taq polymerase may be used to incorporate a mutagenic oligonucleotide primer into an amplified DNA fragment that can then be cloned into an appropriate cloning or expression vector. The PCRTM-mediated mutagenesis procedures of Tomic et al. (1990) and Upender et al. (1995) provide two examples of such protocols. A PCRTM employing a thermostable ligase in addition to a thermostable polymerase may also be used to incorporate a phesphorylated mutagenic oligonucleotide into an amplified DNA fragment that may then be cloned into an appropriate cloning or expression vector. The mutagenesis procedure described by Michael (1994) provides an example of one such protocol.
The preparation of sequence variants of the selected peptide-encoding DNA segments using site-directed mutagenesis is provided as a means of producing potentially useful species and is not meant to be limiting as there are other ways in which sequence variants of peptides and the DNA sequences encoding them may be obtained. For example, recombinant vectors encoding the desired peptide sequence may be treated with mutagenic agents, such as hydroxylamine, to obtain sequence variants.
As used herein, the term “oligonucleotide directed mutagenesis procedure” refers to template-dependent processes and vector-mediated propagation which result in an increase in the concentration of a specific nucleic acid molecule relative to its initial concentration, or in an increase in the concentration of a detectable signal, such as amplification. As used herein, the term “oligonucleotide directed mutagenesis procedure” is intended to refer to a process that involves the template-dependent extension of a primer molecule. The term template dependent process refers to nucleic acid synthesis of an RNA or a DNA molecule wherein the sequence of the newly synthesized strand of nucleic acid is dictated by the well-known rules of complementary base pairing (see, for example, Watson, 1987). Typically, vector mediated methodologies involve the introduction of the nucleic acid fragment into a DNA or RNA vector, the clonal amplification of the vector, and the recovery of the amplified nucleic acid fragment. Examples of such methodologies are provided by U.S. Pat. No. 4,237,224, specifically incorporated herein by reference in its entirety
A number of template dependent processes are available to amplify the target sequences of interest present in a sample. One of the best known amplification methods is the polymerase chain reaction (PCRTM) which is described in detail in U.S. Pat. Nos. 4,683,195, 4,683,202 and 4,800,159 (each of which is specifically incorporated herein by reference in its entirety). Briefly, in PCRTM, two primer sequences are prepared which are complementary to regions on opposite complementary strands of the target sequence. An excess of deoxynucleoside triphosphates are added to a reaction mixture along with a DNA polymerase (e.g., Taq polymerase). If the target sequence is present in a sample, the primers will bind to the target and the polymerase will cause the primers to be extended along the target sequence by adding on nucleotides. By raising and lowering the temperature of the reaction mixture, the extended primers will dissociate from the target to form reaction products, excess primers will bind to the target and to the reaction products and the process is repeated. Preferably a reverse transcriptase PCRTM amplification procedure may be performed in order to quantify the amount of mRNA amplified. Polymerase chain reaction methodologies are well known in the art.
Another method for amplification is the ligase chain reaction (referred to as LCR), disclosed in Eur. Pat. Appl. Publ. No. 320,308, incorporated herein by reference in its entirety. In LCR, two complementary probe pairs are prepared, and in the presence of the target sequence, each pair will bind to opposite complementary strands of the target such that they abut. In the presence of a ligase, the two probe pairs will link to form a single unit. By temperature cycling, as in PCRTM, bound ligated units dissociate from the target and then serve as “target sequences” for ligation of excess probe pairs. U.S. Pat. No. 4,883,750, specifically incorporated herein by reference in its entirety, describes an alternative method of amplification similar to LCR for binding probe pairs to a target sequence.
Qbeta ReplicaseTM, described in Intl. Pat. Appl. Publ. No. PCT/US87/00880, incorporated herein by reference in its entirety, may also be used as still another amplification method in the present invention. In this method, a replicative sequence of RNA which has a region complementary to that of a target is added to a sample in the presence of an RNA polymerase. The polymerase will copy the replicative sequence which can then be detected.
An isothermal amplification method, in which restriction endonucleases and ligases are used to achieve the amplification of target molecules that contain nucleotide 5′-[α-thio]triphosphates in one strand of a restriction site (Walker et al., 1992, incorporated herein by reference in its entirety), may also be useful in the amplification of nucleic acids in the present invention.
Strand Displacement Amplification (SDA) is another method of carrying out isothermal amplification of nucleic acids which involves multiple rounds of strand displacement and synthesis, i.e., nick translation. A similar method, called Repair Chain Reaction (RCR) is another method of amplification which may be useful in the present invention and is involves annealing several probes throughout a region targeted for amplification, followed by a repair reaction in which only two of the four bases are present. The other two bases can be added as biotinylated derivatives for easy detection. A similar approach is used in SDA
Sequences can also be detected using a cyclic probe reaction (CPR). In CPR, a probe having 3′ and 5′ end sequences of non-Cry-specific DNA and an internal sequence of a Cry-specific RNA is hybridized to DNA which is present in a sample. Upon hybridization, the reaction is treated with RNaseH, and the products of the probe identified as distinctive products generating a signal which are released after digestion. The original template is annealed to another cycling probe and the reaction is repeated. Thus, CPR involves amplifying a signal generated by hybridization of a probe to a cry-specific expressed nucleic acid
Still other amplification methods described in Great Britain Pat. Appl. No. 2 202 328, and in Intl. Pat. Appl. Publ. No. PCT/US89/01025, each of which is incorporated herein by reference in its entirety, may be used in accordance with the present invention. In the former application, “modified” primers are used in a PCRTM like, template and enzyme dependent synthesis. The primers may be modified by labeling with a capture moiety (e.g., biotin) and/or a detector moiety (e.g., enzyme). In the latter application, an excess of labeled probes are added to a sample. In the presence of the target sequence, the probe binds and is cleaved catalytically. After cleavage, the target sequence is released intact to be bound by excess probe. Cleavage of the labeled probe signals the presence of the target sequence
Other nucleic acid amplification procedures include transcription-based amplification systems (TAS) (Kwoh et al., 1989; Intl. Pat. Appl. Publ. No. WO 88/10315, incorporated herein by reference in its entirety), including nucleic acid sequence based amplification (NASBA) and 3SR. In NASBA, the nucleic acids can be prepared for amplification by standard phenol/chloroform extraction, heat denaturation of a sample, treatment with lysis buffer and minispin columns for isolation of DNA and RNA or guanidinium chloride extraction of RNA. These amplification techniques involve annealing a primer which has crystal protein-specific sequences. Following polymerization, DNA/RNA hybrids are digested with RNase H while double stranded DNA molecules are heat denatured again. In either case the single stranded DNA is made fully double stranded by addition of second crystal protein-specific primer, followed by polymerization. The double stranded DNA molecules are then multiply transcribed by a polymerase such as T7 or SP6. In an isothermal cyclic reaction, the RNAs are reverse transcribed into double stranded DNA, and transcribed once against with a polymerase such as T7 or SP6. The resulting products, whether truncated or complete, indicate crystal protein-specific sequences.
Eur. Pat. Appl. Publ. No. 329,822, incorporated herein by reference in its entirety, disclose a nucleic acid amplification process involving cyclically synthesizing single-stranded RNA (“ssRNA”), ssDNA, and double-stranded DNA (dsDNA), which may be used in accordance with the present invention. The ssRNA is a first template for a first primer oligonucleotide, which is elongated by reverse transcriptase (RNA-dependent DNA polymerase). The RNA is then removed from resulting DNA:RNA duplex by the action of ribonuclease H(RNase H, an RNase specific for RNA in a duplex with either DNA or RNA). The resultant ssDNA is a second template for a second primer, which also includes the sequences of an RNA polymerase promoter (exemplified by T7 RNA polymerase) 5′ to its homology to its template. This primer is then extended by DNA polymerase (exemplified by the large “Klenow” fragment of E. coli DNA polymerase I), resulting as a double-stranded DNA (“dsDNA”) molecule, having a sequence identical to that of the original RNA between the primers and having additionally, at one end, a promoter sequence. This promoter sequence can be used by the appropriate RNA polymerase to make many RNA copies of the DNA. These copies can then re-enter the cycle leading to very swift amplification. With proper choice of enzymes, this amplification can be done isothermally without addition of enzymes at each cycle. Because of the cyclical nature of this process, the starting sequence can be chosen to be in the form of either DNA or RNA
Intl. Pat. Appl. Publ. No. WO 89/06700, incorporated herein by reference in its entirety, disclose a nucleic acid sequence amplification scheme based on the hybridization of a promoter/primer sequence to a target single-stranded DNA (“ssDNA”) followed by transcription of many RNA copies of the sequence. This scheme is not cyclic; i.e., new templates are not produced from the resultant RNA transcripts. Other amplification methods include “RACE” (Frohman, 1990), and “one-sided PCRTM” (Ohara, 1989) which are well-known to those of skill in the art.
Methods based on ligation of two (or more) oligonucleotides in the presence of nucleic acid having the sequence of the resulting “di-oligonucleotide”, thereby amplifying the di-oligonucleotide (Wu and Dean, 1996, incorporated herein by reference in its entirety), may also be used in the amplification of DNA sequences of the present invention.
4.6 Phage-Resistant Variants
In certain embodiments, one may desired to prepare one or more phage resistant variants of the B. thuringiensis mutants prepared by the methods described herein. To do so, an aliquot of a phage lysate is spread onto nutrient agar and allowed to dry. An aliquot of the phage sensitive bacterial strain is then plated directly over the dried lysate and allowed to dry. The plates are incubated at 30° C. The plates are incubated for 2 days and, at that time, numerous colonies could be seen growing on the agar. Some of these colonies are picked and subcultured onto nutrient agar plates. These apparent resistant cultures are tested for resistance by cross streaking with the phage lysate. A line of the phage lysate is streaked on the plate and allowed to dry. The presumptive resistant cultures are then streaked across the phage line. Resistant bacterial cultures show no lysis anywhere in the streak across the phage line after overnight incubation at 30° C. The resistance to phage is then reconfirmed by plating a lawn of the resistant culture onto a nutrient agar plate. The sensitive strain is also plated in the same manner to serve as the positive control. After drying, a drop of the phage lysate is plated in the center of the plate and allowed to dry. Resistant cultures showed no lysis in the area where the phage lysate has been placed after incubation at 30° C. for 24 hours.
4.7 Crystal Protein Compositions as Insecticides and Methods of Use
Order Coleoptera comprises numerous beetle species including ground beetles, reticulated beetles, skin and larder beetles, long-homed beetles, leaf beetles, weevils, bark beetles, ladybird beetles, soldier beetles, stag beetles, water scavenger beetles, and a host of other beetles. A brief taxonomy of the Order is given at the website http://www.ncbi.nlm.nih.gov/Taxonomy/tax.html.
Particularly important among the Coleoptera are the agricultural pests included within the infraorders Chrysomeliformia and Cucujiformia. Members of the infraorder Chrysomeliformia, including the leaf beetles (Chrysomelidae) and the weevils (Curculionidae), are particularly problematic to agriculture, and are responsible for a variety of insect damage to crops and plants. The infraorder Cucujiformia includes the families Coccinellidae, Cucujidae, Lagridae, Meloidae, Rhipiphoridae, and Tenebrionidae. Within this infraorder, members of the family Chrysomelidae (which includes the genera Exema, Chrysomela, Oreina, Chrysolina, Leptinotarsa, Gonioctena, Oulema, Monozia, Ophraella, Cerotoma, Diabrotica, and Lachnaia), are well-known for their potential to destroy agricultural crops.
As the toxins of the present invention have been shown to be effective in combatting a variety of members of the order Coleoptera, the inventors contemplate that the insects of many Coleopteran genera may be controlled or eradicated using the polypeptide compositions described herein. Likewise, the methods described herein for generating modified polypeptides having enhanced insect specificity may also be useful in extending the range of the insecticidal activity of the modified polypeptides to other insect species within, and outside of, the Order Coleoptera.
As such, the inventors contemplate that the crystal protein compositions disclosed herein will find particular utility as insecticides for topical and/or systemic application to field crops, including but not limited to rice, wheat, alfalfa, corn (maize), soybeans, tobacco, potato, barley, canola (rapeseed), sugarbeet, sugarcane, flax, rye, oats, cotton, sunflower; grasses, such as pasture and turf grasses; fruits, citrus, nuts, trees, shrubs and vegetables; as well as ornamental plants, cacti, succulents, and the like.
Disclosed and claimed is a composition comprising an insecticidally-effective amount of a Cry3Bb* crystal protein composition. The composition preferably comprises the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52. SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, or SEQ ID NO:108 or biologically-functional equivalents thereof.
The insecticide composition may also comprise a Cry3Bb* crystal protein that is encoded by a nucleic acid sequence having the sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5. SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13. SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, or SEQ ID NO:108, or, alternatively, a nucleic acid sequence which hybridizes to the nucleic acid sequence of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5. SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13. SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, or SEQ ID NO:107 under conditions of moderate stringency.
The insecticidal compositions may comprise one or more B. thuringiensis cell types, or one or more cultures of such cells, or, alternatively, a mixture of one or more B. thuringiensis cells which express one or more of the novel crystal proteins of the invention in combination with another insecticidal composition. In certain aspects it may be desirable to prepare compositions which contain a plurality of crystal proteins, either native or modified, for treatment of one or more types of susceptible insects. The B. thuringiensis cells of the invention can be treated prior to formulation to prolong the insecticidal activity when the cells are applied to the environment of the target insect(s). Such treatment can be by chemical or physical means, or by a combination of chemical and/or physical means, so long as the technique does not deleteriously affect the properties of the insecticide, nor diminish the cellular capability in protecting the insecticide. Examples of chemical reagents are halogenerating agents, particularly halogens of atomic no. 17-80. More particularly, iodine can be used under mild conditions and for sufficient time to achieve the desired results. Other suitable techniques include treatment with aldehydes, such as formaldehyde and glutaraldehyde; antiinfectives, such as zephiran chloride; alcohols, such as isopropyl and ethanol; various histologic fixatives, such as Bouin's fixative and Helly's fixative (see Humason, 1967); or a combination of physical (heat) and chemical agents that prolong the activity of the δ-endotoxin produced in the cell when the cell is applied to the environment of the target pest(s). Examples of physical means are short wavelength radiation such as gamma-radiation and X-radiation, freezing, UV irradiation, lyophilization, and the like.
The inventors contemplate that any formulation methods known to those of skill in the art may be employed using the proteins disclosed herein to prepare such bioinsecticide compositions. It may be desirable to formulate whole cell preparations, cell extracts, cell suspensions, cell homogenates, cell lysates, cell supernatants, cell filtrates, or cell pellets of a cell culture (preferably a bacterial cell culture such as a B. thuringiensis cell culture described in Table 3) that expresses one or more cry3Bb* DNA segments to produce the encoded Cry3Bb* protein(s) or peptide(s). The methods for preparing such formulations are known to those of skill in the art, and may include, e.g., desiccation, lyophilization, homogenization, extraction, filtration, centrifugation, sedimentation, or concentration of one or more cultures of bacterial cells, such as B. thuringiensis cells described in Table 3, which express the Cry3Bb* peptide(s) of interest.
In one preferred embodiment, the bioinsecticide composition comprises an oil flowable suspension comprising lysed or unlysed bacterial cells, spores, or crystals which contain one or more of the novel crystal proteins disclosed herein. Preferably the cells are B. thuringiensis cells, however, any such bacterial host cell expressing the novel nucleic acid segments disclosed herein and producing a crystal protein is contemplated to be useful, such as Bacillus spp., including B. megaterium, B. subtilis; B. cereus, Escherichia spp., including E. coli, and/or Pseudomonas spp., including P. cepacia, P., aeruginosa, and P. fluorescens. Alternatively, the oil flowable suspension may consist of a combination of one or more of the following compositions: lysed or unlysed bacterial cells, spores, crystals, and/or purified crystal proteins.
In a second preferred embodiment, the bioinsecticide composition comprises a water dispersible granule or powder. This granule or powder may comprise lysed or unlysed bacterial cells, spores, or crystals which contain one or more of the novel crystal proteins disclosed herein. Preferred sources for these compositions include bacterial cells such as B. thuringiensis cells, however, bacteria of the genera Bacillus, Escherichia, and Pseudomonas which have been transformed with a DNA segment disclosed herein and expressing the crystal protein are also contemplated to be useful. Alternatively, the granule or powder may consist of a combination of one or more of the following compositions: lysed or unlysed bacterial cells, spores, crystals, and/or purified crystal proteins.
In a third important embodiment, the bioinsecticide composition comprises a wettable powder, spray, emulsion, colloid, aqueous or organic solution, dust, pellet, or collodial concentrate. Such a composition may contain either unlysed or lysed bacterial cells, spores, crystals, or cell extracts as described above, which contain one or more of the novel crystal proteins disclosed herein. Preferred bacterial cells are B. thuringiensis cells, however, bacteria such as B. megaterium, B. subtilis, B. cereus, E. coli, or Pseudomonas spp. cells transformed with a DNA segment disclosed herein and expressing the crystal protein are also contemplated to be useful. Such dry forms of the insecticidal compositions may be formulated to dissolve immediately upon wetting, or alternatively, dissolve in a controlled-release, sustained-release, or other time-dependent manner. Alternatively, such a composition may consist of a combination of one or more of the following compositions: lysed or unlysed bacterial cells, spores, crystals, and/or purified crystal proteins.
In a fourth important embodiment, the bioinsecticide composition comprises an aqueous solution or suspension or cell culture of lysed or unlysed bacterial cells, spores, crystals, or a mixture of lysed or unlysed bacterial cells, spores, and/or crystals, such as those described above which contain one or more of the novel crystal proteins disclosed herein. Such aqueous solutions or suspensions may be provided as a concentrated stock solution which is diluted prior to application, or alternatively, as a diluted solution ready-to-apply.
For these methods involving application of bacterial cells, the cellular host containing the Crystal protein gene(s) may be grown in any convenient nutrient medium, where the DNA construct provides a selective advantage, providing for a selective medium so that substantially all or all of the cells retain the B. thuringiensis gene. These cells may then be harvested in accordance with conventional ways. Alternatively, the cells can be treated prior to harvesting.
When the insecticidal compositions comprise B. thuringiensis cells, spores, and/or crystals containing the modified crystal protein(s) of interest, such compositions may be formulated in a variety of ways. They may be employed as wettable powders, granules or dusts, by mixing with various inert materials, such as inorganic minerals (phyllosilicates, carbonates, sulfates, phosphates, and the like) or botanical materials (powdered corncobs, rice hulls, walnut shells, and the like). The formulations may include spreader-sticker adjuvants, stabilizing agents, other pesticidal additives, or surfactants. Liquid formulations may be aqueous-based or non-aqueous and employed as foams, suspensions, emulsifiable concentrates, or the like. The ingredients may include rheological agents, surfactants, emulsifiers, dispersants, or polymers.
Alternatively, the novel Cry3Bb-derived mutated crystal proteins may be prepared by native or recombinant bacterial expression systems in vitro and isolated for subsequent field application. Such protein may be either in crude cell lysates, suspensions, colloids, etc., or alternatively may be purified, refined, buffered, and/or further processed, before formulating in an active biocidal formulation. Likewise, under certain circumstances, it may be desirable to isolate crystals and/or spores from bacterial cultures expressing the crystal protein and apply solutions, suspensions, or collodial preparations of such crystals and/or spores as the active bioinsecticidal composition.
Another important aspect of the invention is a method of controlling coleopteran insects which are susceptible to the novel compositions disclosed herein. Such a method generally comprises contacting the insect or insect population, colony, etc., with an insecticidally-effective amount of a Cry3Bb* crystal protein composition. The method may utilize Cry3Bb* crystal proteins such as those disclosed in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:100, or SEQ ID NO:108, or biologically functional equivalents thereof.
Alternatively, the method may utilize one or more Cry3Bb* crystal proteins which are encoded by the nucleic acid sequences of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5. SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13. SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, SEQ ID NO:101, or SEQ ID NO:107, or by one or more nucleic acid sequences which hybridize to the sequences of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5. SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13. SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, SEQ ID NO:101, or SEQ ID NO:107, under conditions of moderate, or higher, stringency. The methods for identifying sequences which hybridize to those disclosed under conditions of moderate or higher stringency are well-known to those of skill in the art, and are discussed herein.
Regardless of the method of application, the amount of the active component(s) are applied at an insecticidally-effective amount, which will vary depending on such factors as, for example, the specific coleopteran insects to be controlled, the specific plant or crop to be treated, the environmental conditions, and the method, rate, and quantity of application of the insecticidally-active composition.
The insecticide compositions described may be made by formulating either the bacterial cell, crystal and/or spore suspension, or isolated protein component with the desired agriculturally-acceptable carrier. The compositions may be formulated prior to administration in an appropriate means such as lyophilized, freeze-dried, dessicated, or in an aqueous carrier, medium or suitable diluent, such as saline or other buffer. The formulated compositions may be in the form of a dust or granular material, or a suspension in oil (vegetable or mineral), or water or oil/water emulsions, or as a wettable powder, or in combination with any other carrier material suitable for agricultural application. Suitable agricultural carriers can be solid or liquid and are well known in the art. The term “agriculturally-acceptable carrier” covers all adjuvants, e.g., inert components, dispersants, surfactants, tackifiers, binders, etc. that are ordinarily used in insecticide formulation technology; these are well known to those skilled in insecticide formulation. The formulations may be mixed with one or more solid or liquid adjuvants and prepared by various means, e.g. by homogeneously mixing, blending and/or grinding the insecticidal composition with suitable adjuvants using con entional formulation techniques.
The insecticidal compositions of this invention are applied to the environment of the target coleopteran insect, typically onto the foliage of the plant or crop to be protected, by conventional methods, preferably by spraying. The strength and duration of insecticidal application will be set with regard to conditions specific to the particular pest(s), crop(s) to be treated and particular environmental conditions. The proportional ratio of active ingredient to carrier will naturally depend on the chemical nature, solubility, and stability of the insecticidal composition, as well as the particular formulation contemplated.
Other application techniques, e.g., dusting, sprinkling, soaking, soil injection, soil tilling, seed coating, seedling coating, spraying, aerating, misting, atomizing, and the like, are also feasible and may be required under certain circumstances such as e.g., insects that cause root or stalk infestation, or for application to delicate vegetation or ornamental plants. These application procedures are also well-known to those of skill in the art.
The insecticidal composition of the invention may be employed in the method of the invention singly or in combination with other compounds, including and not limited to other pesticides. The method of the invention may also be used in conjunction with other treatments such as surfactants, detergents, polymers or time-release formulations. The insecticidal compositions of the present invention may be formulated for either systemic or topical use.
The concentration of insecticidal composition which is used for environmental, systemic, or foliar application will vary widely depending upon the nature of the particular formulation, means of application, environmental conditions, and degree of biocidal activity. Typically, the bioinsecticidal composition will be present in the applied formulation at a concentration of at least about 1% by weight and may be up to and including about 99% by weight. Dry formulations of the compositions may be from about 1% to about 99% or more by weight of the composition, while liquid formulations may generally comprise from about 1% to about 99% or more of the active ingredient by weight. Formulations which comprise intact bacterial cells will generally contain from about 104 to about 1012 cells/mg
The insecticidal formulation may be administered to a particular plant or target area in one or more applications as needed, with a typical field application rate per hectare ranging on the order of from about 1 g to about 1 kg, 2 kg, 5, kg, or more of active ingredient.
4.8 Nucleic Acid Segments as Hybridization Probes and Primers
In addition to their use in directing the expression of crystal proteins or peptides of the present invention, the nucleic acid sequences contemplated herein also have a variety of other uses. For example, they also have utility as probes or primers in nucleic acid hybridization embodiments. As such, it is contemplated that nucleic acid segments that comprise a sequence region that consists of at least a 14 nucleotide long contiguous sequence that has the same sequence as, or is complementary to, a 14 nucleotide long contiguous DNA segment of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5. SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13. SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, SEQ ID NO:101, or SEQ ID NO:107 will find particular utility. Longer contiguous identical or complementary sequences, e.g., those of about 20, 30, 40, 50, 100, 200, 500, 1000, 2000, 5000, 10000 etc. (including all intermediate lengths and up to and including full-length sequences will also be of use in certain embodiments.
The ability of such nucleic acid probes to specifically hybridize to crystal protein-encoding sequences will enable them to be of use in detecting the presence of complementary sequences in a given sample. However, other uses are envisioned, including the use of the sequence information for the preparation of mutant species primers, or primers for use in preparing other genetic constructions.
Nucleic acid molecules having sequence regions consisting of contiguous nucleotide stretches of 10-14, 15-20, 30, 50, or even of 100-200 nucleotides or so, identical or complementary to DNA sequences of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5. SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13. SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:19, SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:99, SEQ ID NO:101, or SEQ ID NO:107 are particularly contemplated as hybridization probes for use in, e.g., Southern and Northern blotting. Smaller fragments will generally find use in hybridization embodiments, wherein the length of the contiguous complementary region may be varied, such as between about 10-14 and about 100 or 200 nucleotides, but larger contiguous complementary stretches may be used, according to the length complementary sequences one wishes to detect.
The use of a hybridization probe of about 14 nucleotides in length allows the formation of a duplex molecule that is both stable and selective. Molecules having contiguous complementary sequences over stretches greater than 14 bases in length are generally preferred, though, in order to increase stability and selectivity of the hybrid, and thereby improve the quality and degree of specific hybrid molecules obtained. One will generally prefer to design nucleic acid molecules having gene-complementary stretches of 15 to 20 contiguous nucleotides, or even longer where desired.
Of course, fragments may also be obtained by other techniques such as, e.g., by mechanical shearing or by restriction enzyme digestion. Small nucleic acid segments or fragments may be readily prepared by, for example, directly synthesizing the fragment by chemical means, as is commonly practiced using an automated oligonucleotide synthesizer. Also, fragments may be obtained by application of nucleic acid reproduction technology, such as the PCRTM technology of U.S. Pat. Nos. 4,683,195 and 4,683,202 (each incorporated herein by reference), by introducing selected sequences into recombinant vectors for recombinant production, and by other recombinant DNA techniques generally known to those of skill in the art of molecular biology.
Accordingly, the nucleotide sequences of the invention may be used for their ability to selectively form duplex molecules with complementary stretches of DNA fragments. Depending on the application envisioned, one will desire to employ varying conditions of hybridization to achieve varying degrees of selectivity of probe towards target sequence. For applications requiring high selectivity, one will typically desire to employ relatively stringent conditions to form the hybrids, e.g., one will select relatively low salt and/or high temperature conditions, such as provided by about 0.02 M to about 0.15 M NaCl at temperatures of about 50° C. to about 70° C. Such selective conditions tolerate little, if any, mismatch between the probe and the template or target strand, and would be particularly suitable for isolating crystal protein-encoding DNA segments. Detection of DNA segments via hybridization is well-known to those of skill in the art, and the teachings of U.S. Pat. Nos. 4,965,188 and 5,176,995 (each incorporated herein by reference) are exemplary of the methods of hybridization analyses. Teachings such as those found in the texts of Maloy et al., 1994; Segal 1976; Prokop, 1991; and Kuby, 1994, are particularly relevant.
Of course, for some applications, for example, where one desires to prepare mutants employing a mutant primer strand hybridized to an underlying template or where one seeks to isolate crystal protein-encoding sequences from related species, functional equivalents, or the like, less stringent hybridization conditions will typically be needed in order to allow formation of the heteroduplex. In these circumstances, one may desire to employ conditions such as about 0.15 M to about 0.9 M salt, at temperatures ranging from about 20° C. to about 55° C. Cross-hybridizing species can thereby be readily identified as positively hybridizing signals with respect to control hybridizations. In any case, it is generally appreciated that conditions can be rendered more stringent by the addition of increasing amounts of formamide, which serves to destabilize the hybrid duplex in the same manner as increased temperature. Thus, hybridization conditions can be readily manipulated, and thus will generally be a method of choice depending on the desired results.
In certain embodiments, it will be advantageous to employ nucleic acid sequences of the present invention in combination with an appropriate means, such as a label, for determining hybridization. A wide variety of appropriate indicator means are known in the art, including fluorescent, radioactive, enzymatic or other ligands, such as avidin/biotin, which are capable of giving a detectable signal. In preferred embodiments, one will likely desire to employ a fluorescent label or an enzyme tag, such as urease, alkaline phosphatase or peroxidase, instead of radioactive or other environmental undesirable reagents. In the case of enzyme tags, colorimetric indicator substrates are known that can be employed to provide a means visible to the human eye or spectrophotometrically, to identify specific hybridization with complementary nucleic acid-containing samples.
In general, it is envisioned that the hybridization probes described herein will be useful both as reagents in solution hybridization as well as in embodiments employing a solid phase. In embodiments involving a solid phase, the test DNA (or RNA) is adsorbed or otherwise affixed to a selected matrix or surface. This fixed, single-stranded nucleic acid is then subjected to specific hybridization with selected probes under desired conditions. The selected conditions will depend on the particular circumstances based on the particular criteria required (depending, for example, on the G+C content, type of target nucleic acid, source of nucleic acid, size of hybridization probe, etc.). Following washing of the hybridized surface so as to remove nonspecifically bound probe molecules, specific hybridization is detected, or even quantitated, by means of the label.
4.9 Characteristics of Modified Cry3 δ-Endotoxins
The present invention provides novel polypeptides that define a whole or a portion of a B. thuringiensis cry3Bb.60, cry3Bb.11221, cry3Bb.11222, cry3Bb.11223, cry3Bb.11224, cry3Bb.11225, cry3Bb.11226, cry3Bb.11227, cry3Bb.11228, cry3Bb.11229, cry3Bb.11230, cry3Bb.11231, cry3Bb.11232, cry3Bb.11233, cry3Bb.11234, cry3Bb.11235, cry3Bb.11236, cry3Bb.11237, cry3Bb.11238, cry3Bb.11239, cry3Bb.11241, cry3Bb.11242, cry3Bb.11032, cry3Bb.11035, cry3Bb.11036, cry3Bb.11046, cry3Bb.11048, cry3Bb.11051, cry3Bb.11057, cry3Bb.11058, cry3Bb.11081, cry3Bb.11082, cry3Bb.11083, cry3Bb.11084, cry3Bb.11095 and cry3Bb.11098-encoded crystal protein.
4.10 Crystal Protein Nomenclature
The inventors have arbitrarily assigned the designations Cry3Bb.60, Cry3Bb.11221, Cry3Bb.11222, Cry3Bb.11223, Cry3Bb.11224, Cry3Bb.11225, Cry3Bb.11226, Cry3Bb.11227, Cry3Bb.11228, Cry3Bb.11229, Cry3Bb.11230, Cry3Bb.11231, Cry3Bb.11232, Cry3Bb.11233, Cry3Bb.11234, Cry3Bb.11235, Cry3Bb.11236, Cry3Bb.11237, Cry3Bb.11238, Cry3Bb.11239, Cry3Bb.11241, Cry3Bb.11242, Cry3Bb.11032, Cry3Bb.11035, Cry3Bb.11036, Cry3Bb.11046, Cry3Bb.11048, Cry3Bb.11051, Cry3Bb.11057, Cry3Bb.11058, Cry3Bb.11081, Cry3Bb.11082, Cry3Bb.11083, Cry3Bb.11084, Cry3Bb.11095 and Cry3Bb.11098 to the novel proteins of the invention.
Likewise, the arbitrary designations of cry3Bb.60, cry3Bb.11221, cry3Bb.11222, cry3Bb.11223, cry3Bb.11224, cry3Bb.11225, cry3Bb.11226, cry3Bb.11227, cry3Bb.11228, cry3Bb.11229, cry3Bb.11230, cry3Bb.11231, cry3Bb.11232, cry3Bb.11233, cry3Bb.11234, cry3Bb.11235, cry3Bb.11236, cry3Bb.11237, cry3Bb.11238, cry3Bb.11239, cry3Bb.11241, cry3Bb.11242, cry3Bb.11032, cry3Bb.11035, cry3Bb.11036, cry3Bb.11046, cry3Bb.11048, cry3Bb.11051, cry3Bb.11057, cry3Bb.11058, cry3Bb.11081, cry3Bb.11082, cry3Bb.11083, cry3Bb.11084, cry3Bb.11095 and Cry3Bb.11098 have been assigned to the novel nucleic acid sequences which encode these polypeptides, respectively. While formal assignment of gene and protein designations based on the revised nomenclature of crystal protein endotoxins (Table 1) may be made by the committee on the nomenclature of B. thuringiensis, any re-designations of the compositions of the present invention are also contemplated to be fully within the scope of the present disclosure.
4.11 Transformed Host Cells and Transgenic Plants
A bacterium, a yeast cell, or a plant cell or a plant transformed with an expression vector of the present invention is also contemplated. A transgenic bacterium, yeast cell, plant cell or plant derived from such a transformed or transgenic cell is also one aspect of the invention.
Such transformed host cells are often desirable for use in the production of endotoxins and for expression of the various DNA gene constructs disclosed herein. In some aspects of the invention, it is often desirable to modulate, regulate, or otherwise control the expression of the gene segments disclosed herein. Such methods are routine to those of skill in the molecular genetic arts. Typically, when increased or over-expression of a particular gene is desired, various manipulations may be employed for enhancing the expression of the messenger RNA, particularly by using an active promoter, as well as by employing sequences, which enhance the stability of the messenger RNA in the particular transformed host cell.
Typically, the initiation and translational termination region will involve stop codon(s), a terminator region, and optionally, a polyadenylation signal. In the direction of transcription, namely in the 5′ to 3′ direction of the coding or sense sequence, the construct will involve the transcriptional regulatory region, if any, and the promoter, where the regulatory region may be either 5′ or 3′ of the promoter, the ribosomal binding site, the initiation codon, the structural gene having an open reading frame in phase with the initiation codon, the stop codon(s), the polyadenylation signal sequence, if any, and the terminator region. This sequence as a double strand may be used by itself for transformation of a microorganism host, but will usually be included with a DNA sequence involving a marker, where the second DNA sequence may be joined to the δ-endotoxin expression construct during introduction of the DNA into the host.
By a marker is intended a structural gene which provides for selection of those hosts which have been modified or transformed. The marker will normally provide for selective advantage, for example, providing for biocide resistance, e.g., resistance to antibiotics or heavy metals; complementation, so as to provide prototropy to an auxotrophic host, or the like. Preferably, complementation is employed, so that the modified host may not only be selected, but may also be competitive in the field. One or more markers may be employed in the development of the constructs, as well as for modifying the host. The organisms may be further modified by providing for a competitive advantage against other wild-type microorganisms in the field. For example, genes expressing metal chelating agents, e.g., siderophores, may be introduced into the host along with the structural gene expressing the δ-endotoxin. In this manner, the enhanced expression of a siderophore may provide for a competitive advantage for the δ-endotoxin-producing host, so that it may effectively compete with the wild-type microorganisms and stably occupy a niche in the environment.
Where no functional replication system is present, the construct will also include a sequence of at least 50 basepairs (bp), preferably at least about 100 bp, and usually not more than about 1000 bp of a sequence homologous with a sequence in the host. In this way, the probability of legitimate recombination is enhanced, so that the gene will be integrated into the host and stably maintained by the host. Desirably, the δ-endotoxin gene will be in close proximity to the gene providing for complementation as well as the gene providing for the competitive advantage. Therefore, in the event that a δ-endotoxin gene is lost, the resulting organism will be likely to also lose the complementing gene and/or the gene providing for the competitive advantage, so that it will be unable to compete in the environment with the gene retaining the intact construct.
The crystal protein-encoding gene can be introduced between the transcriptional and translational initiation region and the transcriptional and translational termination region, so as to be under the regulatory control of the initiation region. This construct will be included in a plasmid, which will include at least one replication system, but may include more than one, where one replication system is employed for cloning during the development of the plasmid and the second replication system is necessary for functioning in the ultimate host. In addition, one or more markers may be present, which have been described previously. Where integration is desired, the plasmid will desirably include a sequence homologous with the host genome.
The transformants can be isolated in accordance with conventional ways, usually employing a selection technique, which allows for selection of the desired organism as against unmodified organisms or transferring organisms, when present. The transformants then can be tested for pesticidal activity.
Suitable host cells, where the pesticide-containing cells will be treated to prolong the activity of the δ-endotoxin in the cell when the then treated cell is applied to the environment of target pest(s), may include either prokaryotes or eukaryotes, normally being limited to those cells which do not produce substances toxic to higher organisms, such as mammals. However, organisms which produce substances toxic to higher organisms could be used, where the δ-endotoxin is unstable or the level of application sufficiently low as to avoid any possibility of toxicity to a mammalian host. As hosts, of particular interest will be the prokaryotes and the lower eukaryotes, such as fungi. Illustrative prokaryotes, both Gram-negative and -positive, include Enterobacteriaceae, such as Escherichia, Erwinia, Shigella, Salmonella, and Proteus; Bacillaceae; Rhizobiceae, such as Rhizobium; Spirillaceae, such as photobacterium, Zymomonas, Serratia, Aeromonas, Vibrio, Desulfovibdo, Spirillum; Lactobacillaceae; phylloplane organisms such as members of the Pseudomonadaceae (including Pseudomonas spp. and Acetobacter spp.); Azotobacteraceae and Nitrobacteraceae; Flavobacterium spp.; members of the Bacillaceae such as Lactobacillus spp., Bifidobacterium, and Bacillus spp., and the like. Particularly preferred host cells include Pseudomonas aeruginosa, Pseudomonas fluorescens, Bacillus thuringiensis, Escherichia coli, Bacillus subtilis, and the like.
Among eukaryotes are fungi, such as Phycomycetes and Ascomycetes, which includes yeast, such as Schizosaccharomyces; and Basidiomycetes, Rhodotorula, Aureobasidium, Sporobolomyces, Saccharomyces spp., and Sporobolomyces spp.
Characteristics of particular interest in selecting a host cell for purposes of production include ease of introducing the δ-endotoxin gene into the host, availability of expression systems, efficiency of expression, stability of the pesticide in the host, and the presence of auxiliary genetic capabilities. Characteristics of interest for use as a pesticide microcapsule include protective qualities for the pesticide, such as thick cell walls, pigmentation, and intracellular packaging or formation of inclusion bodies; leaf affinity; lack of mammalian toxicity; attractiveness to pests for ingestion; ease of killing and fixing without damage to the δ-endotoxin; and the like. Other considerations include ease of formulation and handling, economics, storage stability, and the like.
The cell will usually be intact and be substantially in the proliferative form when treated, rather than in a spore form, although in some instances spores may be employed. Treatment of the recombinant microbial cell can be done as disclosed infra. The treated cells generally will have enhanced structural stability which will enhance resistance to environmental conditions.
Genes or other nucleic acid segments, as disclosed herein, can be inserted into host cells using a variety of techniques which are well known in the art. For example, a large number of cloning vectors comprising a replication system in E. coli and a marker that permits selection of the transformed cells are available for preparation for the insertion of foreign genes into higher organisms, including plants. The vectors comprise, for example, pBR322, pUC series, M13mp series, pACYC 84, etc. Accordingly, the sequence coding for the δ-endotoxin can be inserted into the vector at a suitable restriction site. The resulting plasmid is used for transformation into E. coli. The E. coli cells are cultivated in a suitable nutrient medium, then harvested and lysed. The plasmid is recovered. Sequence analysis, restriction analysis, electrophoresis, and other biochemical-molecular biological methods are generally carried out as methods of analysis. After each manipulation, the DNA sequence used can be cleaved and joined to the next DNA sequence. Each plasmid sequence can be cloned in the same or other plasmids. Depending on the method of inserting desired genes into the plant, other DNA sequences may be necessary.
Methods for DNA transformation of plant cells include Agrobacterium-mediated plant transformation, protoplast transformation, gene transfer into pollen, injection into reproductive organs, injection into immature embryos and particle bombardment. Each of these methods has distinct advantages and disadvantages. Thus, one particular method of introducing genes into a particular plant strain may not necessarily be the most effective for another plant strain, but it is well known which methods are useful for a particular plant strain.
Suitable methods are believed to include virtually any method by which DNA can be introduced into a cell, such as by Agrobacterium infection, direct delivery of DNA such as, for example, by PEG-mediated transformation of protoplasts (Omirulleh et al., 1993), by desiccation/inhibition-mediated DNA uptake, by electroporation, by agitation with silicon carbide fibers, by acceleration of DNA coated particles, etc. In certain embodiments, acceleration methods are preferred and include, for example, microprojectile bombardment and the like.
Technology for introduction of DNA into cells is well-known to those of skill in the art. Four general methods for delivering a gene into cells have been described: (1) chemical methods (Graham and van der Eb, 1973; Zatloukal et al., 1992); (2) physical methods such as microinjection (Capecchi, 1980), electroporation (Wong and Neumann, 1982; Fromm et al., 1985) and the gene gun (Johnston and Tang, 1994; Fynan et al., 1993); (3) viral vectors (Clapp, 1993; Lu et al., 1993; Eglitis and Anderson, 1988; Eglitis et al., 1988); and (4) receptor-mediated mechanisms (Curiel et al., 1991; 1992; Wagner et al., 1992).
A large number of techniques are available for inserting DNA into a plant host cell. Those techniques include transformation with T-DNA using Agrobacterium tumefaciens or Agrobacterium rhizogenes as transformation agent, fusion, injection, or electroporation as well as other possible methods. If agrobacteria are used for the transformation, the DNA to be inserted has to be cloned into special plasmids, namely either into an intermediate vector or into a binary vector. The intermediate vectors can be integrated into the Ti or Ri plasmid by homologous recombination owing to sequences that are homologous to sequences in the T-DNA. The Ti or Ri plasmid also comprises the vir region necessary for the transfer of the T-DNA.
Intermediate vectors cannot replicate themselves in agrobacteria. The intermediate vector can be transferred into Agrobacterium tumefaciens by means of a helper plasmid (conjugation). Binary vectors can replicate themselves both in E. coli and in agrobacteria.
They comprise a selection marker gene and a linker or polylinker which are framed by the right and left T-DNA border regions. They can be transformed directly into agrobacteria (Holsters et al., 1978). The agrobacterium used as host cell is to comprise a plasmid carrying a vir region. The vir region is necessary for the transfer of the T-DNA into the plant cell. Additional t-DNA may be contained. The bacterium so transformed is used for the transformation of plant cells. Plant explants can advantageously be cultivated with Agrobacterium tumefaciens or Agrobacterium rhizogenes for the transfer of the DNA into the plant cell. Whole plants can then be regenerated from the infected plant material (for example, pieces of leaf, segments of stalk, roots, but also protoplasts or suspension-cultivated cells) in a suitable medium, which may contain antibiotics or biocides for selection. The plants so obtained can then be tested for the presence of the inserted DNA. No special demands are made of the plasmids in the case of injection and electroporation. It is possible to use ordinary plasmids, such as, for example, pUC derivatives. If, for example, the Ti or Ri plasmid is used for the transformation of the plant cell, then at least the right border, but often the right and the left border of the Ti or Ri plasmid T-DNA, has to be joined as the flanking region of the genes to be inserted. The use of T-DNA for the transformation of plant cells has been intensively researched and sufficiently described in Eur. Pat. Appl. No. EP 120 516; Hockema (1985); An et al., 1985, Herrera-Estrella et al., (1983), Bevan et al., (1983), and Klee et al., (1985).
A particularly useful Ti plasmid cassette vector for transformation of dicotyledonous plants consists of the enhanced CaMV35S promoter (EN35S) and the 3′ end including polyadertylation signals from a soybean gene encoding the α′-subunit of β-conglycinin. Between these two elements is a multilinker containing multiple restriction sites for the insertion of genes of interest.
The vector preferably contains a segment of pBR322 which provides an origin of replication in E. coli and a region for homologous recombination with the disarmed T-DNA in Agrobacterium strain ACO; the oriV region from the broad host range plasmid RK1; the streptomycin/spectinomycin resistance gene from Tn7; and a chimeric NPTII gene, containing the CaMV35S promoter and the nopaline synthase (NOS) 3′ end, which provides kanamycin resistance in transformed plant cells.
Optionally, the enhanced CaMV35S promoter may be replaced with the 1.5 kb mannopine synthase (MAS) promoter (Velten et al., 1984). After incorporation of a DNA construct into the vector, it is introduced into A. tumefaciens strain ACO which contains a disarmed Ti plasmid. Cointegrate Ti plasmid vectors are selected and subsequentially may be used to transform a dicotyledonous plant.
A. tumefaciens ACO is a disarmed strain similar to pTiB6SE described by Fraley et al. (1985). For construction of ACO the starting Agrobacterium strain was the strain A208 which contains a nopaline-type Ti plasmid. The Ti plasmid was disarmed in a manner similar to that described by Fraley et al. (1985) so that essentially all of the native T-DNA was removed except for the left border and a few hundred base pairs of T-DNA inside the left border. The remainder of the T-DNA extending to a point just beyond the right border was replaced with a novel piece of DNA including (from left to right) a segment of pBR322, the oriV region from plasmid RK2, and the kanamycin resistance gene from Tn601. The pBR322 and oriV segments are similar to these segments and provide a region of homology for cointegrate formation.
Once the inserted DNA has been integrated in the genome, it is relatively stable there and, as a rule, does not come out again. It normally contains a selection marker that confers on the transformed plant cells resistance to a biocide or an antibiotic, such as kanamycin, G 418, bleomycin, hygromycin, or chloramphenicol, inter alia. The individually employed marker should accordingly permit the selection of transformed cells rather than cells that do not contain the inserted DNA.
4.11.1 Electroporation
The application of brief, high-voltage electric pulses to a variety of animal and plant cells leads to the formation of nanometer-sized pores in the plasma membrane. DNA is taken directly into the cell cytoplasm either through these pores or as a consequence of the redistribution of membrane components that accompanies closure of the pores. Electroporation can be extremely efficient and can be used both for transient expression of clones genes and for establishment of cell lines that carry integrated copies of the gene of interest. Electroporation, in contrast to calcium phosphate-mediated transfection and protoplast fusion, frequently gives rise to cell lines that carry one, or at most a few, integrated copies of the foreign DNA.
The introduction of DNA by means of electroporation, is well-known to those of skill in the art. In this method, certain cell wall-degrading enzymes, such as pectin-degrading enzymes, are employed to render the target recipient cells more susceptible to transformation by electroporation than untreated cells. Alternatively, recipient cells are made more susceptible to transformation, by mechanical wounding. To effect transformation by electroporation one may employ either friable tissues such as a suspension culture of cells, or embryogenic callus, or alternatively, one may transform immature embryos or other organized tissues directly. One would partially degrade the cell walls of the chosen cells by exposing them to pectin-degrading enzymes (pectolyases) or mechanically wounding in a controlled manner. Such cells would then be recipient to DNA transfer by electroporation, which may be carried out at this stage, and transformed cells then identified by a suitable selection or screening protocol dependent on the nature of the newly incorporated DNA.
4.11.2 Microprojectile Bombardment
A further advantageous method for delivering transforming DNA segments to plant cells is microprojectile bombardment. In this method, particles may be coated with nucleic acids and delivered into cells by a propelling force. Exemplary particles include those comprised of tungsten, gold, platinum, and the like.
An advantage of microprojectile bombardment, in addition to it being an effective means of reproducibly stably transforming monocots, is that neither the isolation of protoplasts (Cristou et al., 1988) nor the susceptibility to Agrobacterium infection is required. An illustrative embodiment of a method for delivering DNA into maize cells by acceleration is a Biolistics Particle Delivery System, which can be used to propel particles coated with DNA or cells through a screen, such as a stainless steel or Nytex screen, onto a filter surface covered with corn cells cultured in suspension. The screen disperses the particles so that they are not delivered to the recipient cells in large aggregates. It is believed that a screen intervening between the projectile apparatus and the cells to be bombarded reduces the size of projectiles aggregate and may contribute to a higher frequency of transformation by reducing damage inflicted on the recipient cells by projectiles that are too large.
For the bombardment, cells in suspension are preferably concentrated on filters or solid culture medium. Alternatively, immature embryos or other target cells may be arranged on solid culture medium. The cells to be bombarded are positioned at an appropriate distance below the macroprojectile stopping plate. If desired, one or more screens are also positioned between the acceleration device and the cells to be bombarded. Through the use of techniques set forth herein one may obtain up to 1000 or more foci of cells transiently expressing a marker gene. The number of cells in a focus which express the exogenous gene product 48 hours post-bombardment often range from 1 to 10 and average 1 to 3.
In bombardment transformation, one may optimize the prebombardment culturing conditions and the bombardment parameters to yield the maximum numbers of stable transformants. Both the physical and biological parameters for bombardment are important in this technology. Physical factors are those that involve manipulating the DNA/microprojectile precipitate or those that affect the flight and velocity of either the macro- or microprojectiles. Biological factors include all steps involved in manipulation of cells before and immediately after bombardment, the osmotic adjustment of target cells to help alleviate the trauma associated with bombardment, and also the nature of the transforming DNA, such as linearized DNA or intact supercoiled plasmids. It is believed that pre-bombardment manipulations are especially important for successful transformation of immature embryos.
Accordingly, it is contemplated that one may wish to adjust various of the bombardment parameters in small scale studies to fully optimize the conditions. One may particularly wish to adjust physical parameters such as gap distance, flight distance, tissue distance, and helium pressure. One may also minimize the trauma reduction factors (TRFs) by modifying conditions which influence the physiological state of the recipient cells and which may therefore influence transformation and integration efficiencies. For example, the osmotic state, tissue hydration and the subculture stage or cell cycle of the recipient cells may be adjusted for optimum transformation. The execution of other routine adjustments will be known to those of skill in the art in light of the present disclosure.
4.11.3 Agrobacterium-Mediated Transfer
Agrobacterium-mediated transfer is a widely applicable system for introducing genes into plant cells because the DNA can be introduced into whole plant tissues, thereby bypassing the need for regeneration of an intact plant from a protoplast. The use of Agrobacterium-mediated plant integrating vectors to introduce DNA into plant cells is well known in the art. See, for example, the methods described (Fraley et al., 1985; Rogers et al., 1987). Further, the integration of the Ti-DNA is a relatively precise process resulting in few rearrangements. The region of DNA to be transferred is defined by the border sequences, and intervening DNA is usually inserted into the plant genome as described (Spielmann et al., 1986; Jorgensen et al., 1987).
Modern Agrobacterium transformation vectors are capable of replication in E. coli as well as Agrobacterium, allowing for convenient manipulations as described (Klee et al., 1985). Moreover, recent technological advances in vectors for Agrobacterium-mediated gene transfer have improved the arrangement of genes and restriction sites in the vectors to facilitate construction of vectors capable of expressing various polypeptide coding genes. The vectors described (Rogers et al., 1987), have convenient multi-linker regions flanked by a promoter and a polyadenylation site for direct expression of inserted polypeptide coding genes and are suitable for present purposes. In addition, Agrobacterium containing both armed and disarmed Ti genes can be used for the transformations. In those plant strains where Agrobacterium-mediated transformation is efficient, it is the method of choice because of the facile and defined nature of the gene transfer.
Agrobacterium-mediated transformation of leaf disks and other tissues such as cotyledons and hypocotyls appears to be limited to plants that Agrobacterium naturally infects. Agrobacterium-mediated transformation is most efficient in dicotyledonous plants. Few monocots appear to be natural hosts for Agrobacterium, although transgenic plants have been produced in asparagus using Agrobacterium vectors as described (Bytebier et al., 1987). Therefore, commercially important cereal grains such as rice, corn, and wheat must usually be transformed using alternative methods. However, as mentioned above, the transformation of asparagus using Agrobacterium can also be achieved (see, for example, Bytebier et al. 1987).
A transgenic plant formed using Agrobacterium transformation methods typically contains a single gene on one chromosome. Such transgenic plants can be referred to as being heterozygous for the added gene. However, inasmuch as use of the word “heterozygous” usually implies the presence of a complementary gene at the same locus of the second chromosome of a pair of chromosomes, and there is no such gene in a plant containing one added gene as here, it is believed that a more accurate name for such a plant is an independent segregant, because the added, exogenous gene segregates independently during mitosis and meiosis.
More preferred is a transgenic plant that is homozygous for the added structural gene; i.e., a transgenic plant that contains two added genes, one gene at the same locus on each chromosome of a chromosome pair. A homozygous transgenic plant can be obtained by sexually mating (selfing) an independent segregant transgenic plant that contains a single added gene, germinating some of the seed produced and analyzing the resulting plants produced for enhanced carboxylase activity relative to a control (native, non-transgenic) or an independent segregant transgenic plant.
It is to be understood that two different transgenic plants can also be mated to produce offspring that contain two independently segregating added, exogenous genes. Selfing of appropriate progeny can produce plants that are homozygous for both added, exogenous genes that encode a polypeptide of interest. Back-crossing to a parental plant and out-crossing with a non-transgenic plant are also contemplated.
Transformation of plant protoplasts can be achieved using methods based on calcium phosphate precipitation, polyethylene glycol treatment, electroporation, and combinations of these treatments (see, e.g., Potrykus et al., 1985; Lorz et al., 1985; Fromm et al., 1985; Uchimiya et al., 1986; Callis et al., 1987; Marcotte et al., 1988).
Application of these systems to different plant strains depends upon the ability to regenerate that particular plant strain from protoplasts. Illustrative methods for the regeneration of cereals from protoplasts are described (Fujimura et al., 1985; Toriyama et al., 1986; Yamada et al., 1986; Abdullah et al., 1986).
To transform plant strains that cannot be successfully regenerated from protoplasts, other ways to introduce DNA into intact cells or tissues can be utilized. For example, regeneration of cereals from immature embryos or explants can be effected as described (Vasil, 1988). In addition, “particle gun” or high-velocity microprojectile technology can be utilized (Vasil, 1992).
Using that latter technology, DNA is carried through the cell wall and into the cytoplasm on the surface of small metal particles as described (Klein et al., 1987; Klein et al., 1988; McCabe et al., 1988). The metal particles penetrate through several layers of cells and thus allow the transformation of cells within tissue explants.
4.11.4 Gene Expression in Plants
Although great progress has been made in recent years with respect to preparation of transgenic plants which express bacterial proteins such as B. thuringiensis crystal proteins, the results of expressing native bacterial genes in plants are often disappointing. Unlike microbial genetics, little was known by early plant geneticists about the factors which affected heterologous expression of foreign genes in plants. In recent years, however, several potential factors have been implicated as responsible in varying degrees for the level of protein expression from a particular coding sequence. For example, scientists now know that maintaining a significant level of a particular mRNA in the cell is indeed a critical factor. Unfortunately, the causes for low steady state levels of mRNA encoding foreign proteins are many. First, full length RNA synthesis may not occur at a high frequency. This could, for example, be caused by the premature termination of RNA during transcription or due to unexpected mRNA processing during transcription. Second, full length RNA may be produced in the plant cell, but then processed (splicing, polyA addition) in the nucleus in a fashion that creates a nonfunctional mRNA. If the RNA is not properly synthesized, terminated and polyadenylated, it cannot move to the cytoplasm for translation. Similarly, in the cytoplasm, if mRNAs have reduced half lives (which are determined by their primary or secondary sequence) insufficient protein product will be produced. In addition, there is an effect, whose magnitude is uncertain, of translational efficiency on mRNA half-life. In addition, every RNA molecule folds into a particular structure, or perhaps family of structures, which is determined by its sequence. The particular structure of any RNA might lead to greater or lesser stability in the cytoplasm. Structure per se is probably also a determinant of mRNA processing in the nucleus. Unfortunately, it is impossible to predict, and nearly impossible to determine, the structure of any RNA (except for tRNA) in vitro or in vivo. However, it is likely that dramatically changing the sequence of an RNA will have a large effect on its folded structure It is likely that structure per se or particular structural features also have a role in determining RNA stability.
To overcome these limitations in foreign gene expression, researchers have identified particular sequences and signals in RNAs that have the potential for having a specific effect on RNA stability. In certain embodiments of the invention, therefore, there is a desire to optimize expression of the disclosed nucleic acid segments in planta. One particular method of doing so, is by alteration of the bacterial gene to remove sequences or motifs which decrease expression in a transformed plant cell. The process of engineering a coding sequence for optimal expression in planta is often referred to as “plantizing” a DNA sequence.
Particularly problematic sequences are those which are A+T rich. Unfortunately, since B. thuringiensis has an A+T rich genome, native crystal protein gene sequences must often be modified for optimal expression in a plant. The sequence motif ATTTA (or AUUUA as it appears in RNA) has been implicated as a destabilizing sequence in mammalian cell mRNA (Shaw and Kamen, 1986). Many short lived mRNAs have A+T rich 3′ untranslated regions, and these regions often have the ATTTA sequence, sometimes present in multiple copies or as multimers (e.g., ATTTATTTA . . . ). Shaw and Kamen showed that the transfer of the 3′ end of an unstable mRNA to a stable RNA (globin or VA1) decreased the stable RNA's half life dramatically. They further showed that a pentamer of ATTTA had a profound destabilizing effect on a stable message, and that this signal could exert its effect whether it was located at the 3′ end or within the coding sequence. However, the number of ATTTA sequences and/or the sequence context in which they occur also appear to be important in determining whether they function as destabilizing sequences. Shaw and Kamen showed that a trimer of ATTTA had much less effect than a pentamer on mRNA stability and a dimer or a monomer had no effect on stability (Shaw and Kamen, 1987). Note that multimers of ATTTA such as a pentamer automatically create an A+T rich region. This was shown to be a cytoplasmic effect, not nuclear. In other unstable mRNAs, the ATTTA sequence may be present in only a single copy, but it is often contained in an A+T rich region. From the animal cell data collected to date, it appears that ATTTA at least in some contexts is important in stability, but it is not yet possible to predict which occurrences of ATTTA are destabiling elements or whether any of these effects are likely to be seen in plants.
Some studies on mRNA degradation in animal cells also indicate that RNA degradation may begin in some cases with nucleolytic attack in A+T rich regions. It is not clear if these cleavages occur at ATTTA sequences. There are also examples of mRNAs that have differential stability depending on the cell type in which they are expressed or on the stage within the cell cycle at which they are expressed. For example, histone mRNAs are stable during DNA synthesis but unstable if DNA synthesis is disrupted. The 3′ end of some histone mRNAs seems to be responsible for this effect (Pandey and Marzluff, 1987). It does not appear to be mediated by ATTTA, nor is it clear what controls the differential stability of this mRNA. Another example is the differential stability of IgG mRNA in B lymphocytes during B cell maturation (Genovese and Milcarek, 1988). A final example is the instability of a mutant β-thallesemic globin mRNA. In bone marrow cells, where this gene is normally expressed, the mutant mRNA is unstable, while the wild-type mRNA is stable. When the mutant gene is expressed in HeLa or L cells in vitro, the mutant mRNA shows no instability (Lim et al., 1988). These examples all provide evidence that mRNA stability can be mediated by cell type or cell cycle specific factors. Furthermore this type of instability is not yet associated with specific sequences. Given these uncertainties, it is not possible to predict which RNAs are likely to be unstable in a given cell. In addition, even the ATTTA motif may act differentially depending on the nature of the cell in which the RNA is present. Shaw and Kamen (1987) have reported that activation of protein kinase C can block degradation mediated by ATTTA.
The addition of a polyadenylate string to the 3′ end is common to most eukaryotic mRNAs, both plant and animal. The currently accepted view of polyA addition is that the nascent transcript extends beyond the mature 3′ terminus. Contained within this transcript are signals for polyadenylation and proper 3′ end formation. This processing at the 3′ end involves cleavage of the mRNA and addition of polyA to the mature 3′ end. By searching for consensus sequences near the polyA tract in both plant and animal mRNAs, it has been possible to identify consensus sequences that apparently are involved in polyA addition and 3′ end cleavage. The same consensus sequences seem to be important to both of these processes. These signals are typically a variation on the sequence AATAAA. In animal cells, some variants of this sequence that are functional have been identified; in plant cells there seems to be an extended range of functional sequences (Wickens and Stephenson, 1984; Dean et al., 1986). Because all of these consensus sequences are variations on AATAAA, they all are A+T rich sequences. This sequence is typically found 15 to 20 bp before the polyA tract in a mature mRNA. Studies in animal cells indicate that this sequence is involved in both polyA addition and 3′ maturation. Site directed mutations in this sequence can disrupt these functions (Conway and Wickens, 1988; Wickens et al., 1987). However, it has also been observed that sequences up to 50 to 100 bp 3′ to the putative polyA signal are also required; i.e., a gene that has a normal AATAAA but has been replaced or disrupted downstream does not get properly polyadenylated (Gil and Proudfoot, 1984; Sadofsky and Alwine, 1984; McDevitt et al., 1984). That is, the polyA signal itself is not sufficient for complete and proper processing. It is not yet known what specific downstream sequences are required in addition to the polyA signal, or if there is a specific sequence that has this function. Therefore, sequence analysis can only identify potential polyA signals.
In naturally occurring mRNAs that are normally polyadenylated, it has been observed that disruption of this process, either by altering the polyA signal or other sequences in the mRNA, profound effects can be obtained in the level of functional mRNA. This has been observed in several naturally occurring mRNAs, with results that are gene-specific so far.
It has been shown that in natural mRNAs proper polyadenylation is important in mRNA accumulation, and that disruption of this process can effect mRNA levels significantly. However, insufficient knowledge exists to predict the effect of changes in a normal gene. In a heterologous gene, it is even harder to predict the consequences. However, it is possible that the putative sites identified are dysfunctional. That is, these sites may not act as proper polyA sites, but instead function as aberrant sites that give rise to unstable mRNAs.
In animal cell systems, AATAAA is by far the most common signal identified in mRNAs upstream of the polyA, but at least four variants have also been found (Wickens and Stephenson, 1984). In plants, not nearly so much analysis has been done, but it is clear that multiple sequences similar to AATAAA can be used. The plant sites in Table 5 called major or minor refer only to the study of Dean et al. (1986) which analyzed only three types of plant gene. The designation of polyadenylation sites as major or minor refers only to the frequency of their occurrence as functional sites in naturally occurring genes that have been analyzed. In the case of plants this is a very limited database. It is hard to predict with any certainty that a site designated major or minor is more or less likely to function partially or completely when found in a heterologous gene such as those encoding the crystal proteins of the present invention.







TABLE 5





POLYADENYLATION SITES IN PLANT GENES

















PA
AATAAA
Major consensus site


 


P1A
AATAAT
Major plant site


 


P2A
AACCAA
Minor plant site


 


P3A
ATATAA
′′


 


P4A
AATCAA
′′


 


P5A
ATACTA
′′


 


P6A
ATAAAA
′′


 


P7A
ATGAAA
′′


 


P8A
AAGCAT
′′


 


P9A
ATTAAT
′′


 


P10A
ATACAT
′′


 


P11A
AAAATA
′′


 


P12A
ATTAAA
Minor animal site


 


P13A
AATTAA
′′


 


P14A
AATACA
′′


 


P15A
CATAAA
′′









The present invention provides a method for preparing synthetic plant genes which genes express their protein product at levels significantly higher than the wild-type genes which were commonly employed in plant transformation heretofore. In another aspect, the present invention also provides novel synthetic plant genes which encode non-plant proteins.
As described above, the expression of native B. thuringiensis genes in plants is often problematic. The nature of the coding sequences of B. thuringiensis genes distinguishes them from plant genes as well as many other heterologous genes expressed in plants. In particular, B. thuringiensis genes are very rich ( ̃62%) in adenine (A) and thymine (T) while plant genes and most other bacterial genes which have been expressed in plants are on the order of 45-55% A+T.
Due to the degeneracy of the genetic code and the limited number of codon choices for any amino acid, most of the “excess” A+T of the structural coding sequences of some Bacillus species are found in the third position of the codons. That is, genes of some Bacillus species have A or T as the third nucleotide in many codons. Thus A+T content in part can determine codon usage bias. In addition, it is clear that genes evolve for maximum function in the organism in which they evolve. This means that particular nucleotide sequences found in a gene from one organism, where they may play no role except to code for a particular stretch of amino acids, have the potential to be recognized as gene control elements in another organism (such as transcriptional promoters or terminators, polyA addition sites, intron splice sites, or specific mRNA degradation signals). It is perhaps surprising that such misread signals are not a more common feature of heterologous gene expression, but this can be explained in part by the relatively homogeneous A+T content ( ̃50%) of many organisms. This A+T content plus the nature of the genetic code put clear constraints on the likelihood of occurrence of any particular oligonucleotide sequence. Thus, a gene from E. coli with a 50% A+T content is much less likely to contain any particular A+T rich segment than a gene from B. thuringiensis. 
Typically, to obtain high-level expression of the S-endotoxin genes in plants, existing structural coding sequence (“structural gene”) which codes for the S-endotoxin are modified by removal of ATTTA sequences and putative polyadenylation signals by site directed mutagenesis of the DNA comprising the structural gene. It is most preferred that substantially all the polyadenylation signals and ATTTA sequences are removed although enhanced expression levels are observed with only partial removal of either of the above identified sequences. Alternately if a synthetic gene is prepared which codes for the expression of the subject protein, codons are selected to avoid the ATTTA sequence and putative polyadenylation signals. For purposes of the present invention putative polyadenylation signals include, but are not necessarily limited to, AATAAA, AATAAT, AACCAA, ATATAA, AATCAA, ATACTA, ATAAAA, ATGAAA, AAGCAT, ATTAAT, ATACAT, AAAATA, ATTAAA, AATTAA, AATACA and CATAAA. In replacing the ATTTA sequences and polyadenylation signals, codons are preferably utilized which avoid the codons which are rarely found in plant genomes.
The selected DNA sequence is scanned to identify regions with greater than four consecutive adenine (A) or thymine (T) nucleotides. The A+T regions are scanned for potential plant polyadenylation signals. Although the absence of five or more consecutive A or T nucleotides eliminates most plant polyadenylation signals, if there are more than one of the minor polyadenylation signals identified within ten nucleotides of each other, then the nucleotide sequence of this region is preferably altered to remove these signals while maintaining the original encoded amino acid sequence.
The second step is to consider the about 15 to about 30 or so nucleotide residues surrounding the A+T rich region identified in step one. If the A+T content of the surrounding region is less than 80%, the region should be examined for polyadenylation signals. Alteration of the region based on polyadenylation signals is dependent upon (1) the number of polyadenylation signals present and (2) presence of a major plant polyadenylation signal.
The extended region is examined for the presence of plant polyadenylation signals. The polyadenylation signals are removed by site-directed mutagenesis of the DNA sequence. The extended region is also examined for multiple copies of the ATTTA sequence which are also removed by mutagenesis.
It is also preferred that regions comprising many consecutive A+T bases or G+C bases are disrupted since these regions are predicted to have a higher likelihood to form hairpin structure due to self-complementarity. Therefore, insertion of heterogeneous base pairs would reduce the likelihood of self-complementary secondary structure formation which are known to inhibit transcription and/or translation in some organisms. In most cases, the adverse effects may be minimized by using sequences which do not contain more than five consecutive A+T or G+C.
4.11.5 Synthetic Oligonucleotides for Mutagenesis
When oligonucleotides are used in the mutagenesis, it is desirable to maintain the proper amino acid sequence and reading frame, without introducing common restriction sites such as BglII, HindIII, SacI, KpnI, EcoRI, NcoI, PstI and SalI into the modified gene. These restriction sites are found in poly-linker insertion sites of many cloning vectors. Of course, the introduction of new polyadenylation signals, ATTTA sequences or consecutive stretches of more than five A+T or G+C, should also be avoided. The preferred size for the oligonucleotides is about 40 to about 50 bases, but fragments ranging from about 18 to about 100 bases have been utilized. In most cases, a minimum of about 5 to about 8 base pairs of homology to the template DNA on both ends of the synthesized fragment are maintained to insure proper hybridization of the primer to the template. The oligonucleotides should avoid sequences longer than five base pairs A+T or G+C. Codons used in the replacement of wild-type codons should preferably avoid the TA or CG doublet wherever possible. Codons are selected from a plant preferred codon table (such as Table 6 below) so as to avoid codons which are rarely found in plant genomes, and efforts should be made to select codons to preferably adjust the G-+C content to about 50%.







TABLE 6







PREFERRED CODON USAGE IN PLANTS











Percent Usage


Amino Acid
Codon
in Plants












ARG
CGA
7



CGC
11



CGG
5



CGU
25



AGA
29



AGG
23


 


LEU
CUA
8



CUC
20



CUG
10



CUU
28



UUA
5



UUG
30


 


SER
UCA
14



UCC
26



UCG
3



UCU
21



AGC
21



AGU
15


 


THR
ACA
21



ACC
41



ACG
7



ACU
31


 


PRO
CCA
45



CCC
19



CCG
9



CCU
26


 


ALA
GCA
23



GCC
32



GCG
3



GCU
41


 


GLY
GGA
32



GGC
20



GGG
11



GGU
37


 


ILE
AUA
12



AUC
45



AUU
43


 


VAL
GUA
9



GUC
20



GUG
28



GUU
43


 


LYS
AAA
36



AAG
64


 


ASN
AAC
72



AAU
28


 


GLN
CAA
64



CAG
36


 


HIS
CAC
65



CAU
35


 


GLU
GAA
48



GAG
52


 


ASP
GAC
48



GAU
52


 


TYR
UAC
68



UAU
32


 


CYS
UGC
78



UGU
22


 


PHE
UUC
56



UUU
44


 


MET
AUG
100


 


TRP
UGG
100









Regions with many consecutive A+T bases or G+C bases are predicted to have a higher likelihood to form hairpin structures due to self-complementarity. Disruption of these regions by the insertion of heterogeneous base pairs is preferred and should reduce the likelihood of the formation of self-complementary secondary structures such as hairpins which are known in some organisms to inhibit transcription (transcriptional terminators) and translation (attenuators).
Alternatively, a completely synthetic gene for a given amino acid sequence can be prepared, with regions of five or more consecutive A+T or G+C nucleotides being avoided. Codons are selected avoiding the TA and CG doublets in codons whenever possible. Codon usage can be normalized against a plant preferred codon usage table (such as Table 6) and the G+C content preferably adjusted to about 50%. The resulting sequence should be examined to ensure that there are minimal putative plant polyadenylation signals and ATTTA sequences. Restriction sites found in commonly used cloning vectors are also preferably avoided. However, placement of several unique restriction sites throughout the gene is useful for analysis of gene expression or construction of gene variants.
4.11.6 “Plantized” Gene Constructs
The expression of a plant gene which exists in double-stranded DNA form involves transcription of messenger RNA (mRNA) from one strand of the DNA by RNA polymerase enzyme, and the subsequent processing of the mRNA primary transcript inside the nucleus. This processing involves a 3′ non-translated region which adds polyadenylate nucleotides to the 3′ end of the RNA. Transcription of DNA into mRNA is regulated by a region of DNA usually referred to as the “promoter.” The promoter region contains a sequence of bases that signals RNA polymerase to associate with the DNA and to initiate the transcription of mRNA using one of the DNA strands as a template to make a corresponding strand of RNA.
A number of promoters which are active in plant cells have been described in the literature. These include the nopaline synthase (NOS) and octopine synthase (OCS) promoters (which are carried on tumor-inducing plasmids of Agrobacterium tumefaciens), the Cauliflower Mosaic Virus (CaMV) 19S and 35S promoters, the light-inducible promoter from the small subunit of ribulose bis-phosphate carboxylase (ssRUBISCO, a very abundant plant polypeptide) and the mannopine synthase (MAS) promoter (Velten et al., 1984 and Velten and Schell, 1985). All of these promoters have been used to create various types of DNA constructs which have been expressed in plants (see e.g., Int. Pat. Appl. Publ. No. WO 84/02913).
Promoters which are known or are found to cause transcription of RNA in plant cells can be used in the present invention. Such promoters may be obtained from plants or plant viruses and include, but are not limited to, the CaMV35S promoter and promoters isolated from plant genes such as ssRUBISCO genes. As described below, it is preferred that the particular promoter selected should be capable of causing sufficient expression to result in the production of an effective amount of protein.
The promoters used in the DNA constructs (i.e. chimeric plant genes) of the present invention may be modified, if desired, to affect their control characteristics. For example, the CaMV35S promoter may be ligated to the portion of the ssRUBISCO gene that represses the expression of ssRUBISCO in the absence of light, to create a promoter which is active in leaves but not in roots. The resulting chimeric promoter may be used as described herein. For purposes of this description, the phrase “CaMV35S” promoter thus includes variations of CaMV35S promoter, e.g., promoters derived by means of ligation with operator regions, random or controlled mutagenesis, etc. Furthermore, the promoters may be altered to contain multiple “enhancer sequences” to assist in elevating gene expression.
The RNA produced by a DNA construct of the present invention also contains a 5′ non-translated leader sequence. This sequence can be derived from the promoter selected to express the gene, and can be specifically modified so as to increase translation of the mRNA. The 5′ non-translated regions can also be obtained from viral RNA's, from suitable eukaryotic genes, or from a synthetic gene sequence. The present invention is not limited to constructs, as presented in the following examples. Rather, the non-translated leader sequence can be part of the 5′ end of the non-translated region of the coding sequence for the virus coat protein, or part of the promoter sequence, or can be derived from an unrelated promoter or coding sequence. In any case, it is preferred that the sequence flanking the initiation site conform to the translational consensus sequence rules for enhanced translation initiation reported by Kozak (1984).
The cry DNA constructs of the present invention may also contain one or more modified or fully-synthetic structural coding sequences which have been changed to enhance the performance of the cry gene in plants. The structural genes of the present invention may optionally encode a fusion protein comprising an amino-terminal chloroplast transit peptide or secretory signal sequence.
The DNA construct also contains a 3′ non-translated region. The 3′ non-translated region contains a polyadenylation signal which functions in plants to cause the addition of polyadenylate nucleotides to the 3′ end of the viral RNA. Examples of suitable 3′ regions are (1) the 3′ transcribed, non-translated regions containing the polyadenylation signal of Agrobacterium tumor-inducing (Ti) plasmid genes, such as the nopaline synthase (NOS) gene, and (2) plant genes like the soybean storage protein (7S) genes and the small subunit of the RuBP carboxylase (E9) gene.
4.12 Methods for Producing Insect-Resistant Transgenic Plants
By transforming a suitable host cell, such as a plant cell, with a recombinant cry* gene-containing segment, the expression of the encoded crystal protein (i.e., a bacterial crystal protein or polypeptide having insecticidal activity against coleopterans) can result in the formation of insect-resistant plants.
By way of example, one may utilize an expression vector containing a coding region for a B. thuringiensis crystal protein and an appropriate selectable marker to transform a suspension of embryonic plant cells, such as wheat or corn cells using a method such as particle bombardment (Maddock et al., 1991; Vasil et al., 1992) to deliver the DNA coated on microprojectiles into the recipient cells. Transgenic plants are then regenerated from transformed embryonic calli that express the insecticidal proteins.
The formation of transgenic plants may also be accomplished using other methods of cell transformation which are known in the art such as Agrobacterium-mediated DNA transfer (Fraley et al., 1983). Alternatively, DNA can be introduced into plants by direct DNA transfer into pollen (Zhou et al., 1983; Hess, 1987; Luo et al., 1988), by injection of the DNA into reproductive organs of a plant (Pena et al., 1987), or by direct injection of DNA into the cells of immature embryos followed by the rehydration of desiccated embryos (Neuhaus et al., 1987; Benbrook et al., 1986).
The regeneration, development, and cultivation of plants from single plant protoplast transformants or from various transformed explants is well known in the art (Weissbach and Weissbach, 1988). This regeneration and growth process typically includes the steps of selection of transformed cells, culturing those individualized cells through the usual stages of embryonic development through the rooted plantlet stage. Transgenic embryos and seeds are similarly regenerated. The resulting transgenic rooted shoots are thereafter planted in an appropriate plant growth medium such as soil.
The development or regeneration of plants containing the foreign, exogenous gene that encodes a polypeptide of interest introduced by Agrobacterium from leaf explants can be achieved by methods well known in the art such as described (Horsch et al., 1985). In this procedure, transformants are cultured in the presence of a selection agent and in a medium that induces the regeneration of shoots in the plant strain being transformed as described (Fraley et al., 1983).
This procedure typically produces shoots within two to four months and those shoots are then transferred to an appropriate root-inducing medium containing the selective agent and an antibiotic to prevent bacterial growth. Shoots that rooted in the presence of the selective agent to form plantlets are then transplanted to soil or other media to allow the production of roots. These procedures vary depending upon the particular plant strain employed, such variations being well known in the art.
Preferably, the regenerated plants are self-pollinated to provide homozygous transgenic plants, as discussed before. Otherwise, pollen obtained from the regenerated plants is crossed to seed-grown plants of agronomically important, preferably inbred lines. Conversely, pollen from plants of those important lines is used to pollinate regenerated plants. A transgenic plant of the present invention containing a desired polypeptide is cultivated using methods well known to one skilled in the art.
Such plants can form germ cells and transmit the transformed trait(s) to progeny plants. Likewise, transgenic plants can be grown in the normal manner and crossed with plants that have the same transformed hereditary factors or other hereditary factors. The resulting hybrid individuals have the corresponding phenotypic properties. A transgenic plant of this invention thus has an increased amount of a coding region (e.g., a mutated cry gene) that encodes the mutated Cry polypeptide of interest. A preferred transgenic plant is an independent segregant and can transmit that gene and its activity to its progeny. A more preferred transgenic plant is homozygous for that gene, and transmits that gene to all of its offspring on sexual mating.
Seed from a transgenic plant may be grown in the field or greenhouse, and resulting sexually mature transgenic plants are self-pollinated to generate true breeding plants. The progeny from these plants become true breeding lines that are evaluated for, by way of example, increased insecticidal capacity against coleopteran insects, preferably in the field, under a range of environmental conditions. The inventors contemplate that the present invention will find particular utility in the creation of transgenic plants of commercial interest including various grasses, grains, fibers, tubers, legumes, ornamental plants, cacti, succulents, fruits, berries, and vegetables, as well as a number of nut- and fruit-bearing trees and plants.
4.13 Methods for Producing Combinatorial Cry3* Variants
Crystal protein mutants containing substitutions in one or more domains may be constructed via a number of techniques. For instance, sequences of highly related genes can be readily shuffled using the PCRTM-based technique described by Stemmer (1994). Alternatively, if suitable restriction sites are available, the mutations of one cry gene may be combined with the mutations of a second cry gene by routine subcloning methodologies. If a suitable restriction site is not available, one may be generated by oligonucleotide directed mutagenesis using any number of procedures known to those skilled in the art. Alternatively, splice-overlap extension PCRTM (Horton et al., 1989) may be used to combine mutations in different regions of a crystal protein. In this procedure, overlapping DNA fragments generated by the PCRTM and containing different mutations within their unique sequences may be annealed and used as a template for amplification using flanking primers to generate a hybrid gene sequence. Finally, cry* mutants may be combined by simply using one cry mutant as a template for oligonucleotide-directed mutagenesis using any number of protocols such as those described herein.
4.14 Isolating Homologous Gene and Gene Fragments
The genes and δ-endotoxins according to the subject invention include not only the full length sequences disclosed herein but also fragments of these sequences, or fusion proteins, which retain the characteristic insecticidal activity of the sequences specifically exemplified herein.
It should be apparent to a person skill in this art that insecticidal δ-endotoxins can be identified and obtained through several means. The specific genes, or portions thereof, may be obtained from a culture depository, or constructed synthetically, for example, by use of a gene machine. Variations of these genes may be readily constructed using standard techniques for making point mutations. Also, fragments of these genes can be made using commercially available exonucleases or endonucleases according to standard procedures.
For example, enzymes such as Bal31 or site-directed mutagenesis can be used to systematically cut off nucleotides from the ends of these genes. Also, genes which code for active fragments may be obtained using a variety of other restriction enzymes. Proteases may be used to directly obtain active fragments of these δ-endotoxins.
Equivalent δ-endotoxins and/or genes encoding these equivalent δ-endotoxins can also be isolated from Bacillus strains and/or DNA libraries using the teachings provided herein. For example, antibodies to the δ-endotoxins disclosed and claimed herein can be used to identify and isolate other δ-endotoxins from a mixture of proteins. Specifically, antibodies may be raised to the portions of the δ-endotoxins which are most constant and most distinct from other B. thuringiensis δ-endotoxins. These antibodies can then be used to specifically identify equivalent δ-endotoxins with the characteristic insecticidal activity by immunoprecipitation, enzyme linked immunoassay (ELISA), or Western blotting.
A further method for identifying the δ-endotoxins and genes of the subject invention is through the use of oligonucleotide probes. These probes are nucleotide sequences having a detectable label. As is well known in the art, if the probe molecule and nucleic acid sample hybridize by forming a strong bond between the two molecules, it can be reasonably assumed that the probe and sample are essentially identical. The probe's detectable label provides a means for determining in a known manner whether hybridization has occurred. Such a probe analysis provides a rapid method for identifying formicidal δ-endotoxin genes of the subject invention.
The nucleotide segments which are used as probes according to the invention can be synthesized by use of DNA synthesizers using standard procedures. In the use of the nucleotide segments as probes, the particular probe is labeled with any suitable label known to those skilled in the art, including radioactive and non-radioactive labels. Typical radioactive labels include 32P, 125I, 35S, or the like. A probe labeled with a radioactive isotope can be constructed from a nucleotide sequence complementary to the DNA sample by a conventional nick translation reaction, using a DNase and DNA polymerase. The probe and sample can then be combined in a hybridization buffer solution and held at an appropriate temperature until annealing occurs. Thereafter, the membrane is washed free of extraneous materials, leaving the sample and bound probe molecules typically detected and quantified by autoradiography and/or liquid scintillation counting.
Non-radioactive labels include, for example, ligands such as biotin or thyroxine, as well as enzymes such as hydrolases or peroxidases, or the various chemiluminescers such as luciferin, or fluorescent compounds like fluorescein and its derivatives. The probe may also be labeled at both ends with different types of labels for ease of separation, as, for example, by using an isotopic label at the end mentioned above and a biotin label at the other end.
Duplex formation and stability depend on substantial complementarity between the two strands of a hybrid, and, as noted above, a certain degree of mismatch can be tolerated. Therefore, the probes of the subject invention include mutations (both single and multiple), deletions, insertions of the described sequences, and combinations thereof, wherein said mutations, insertions and deletions permit formation of stable hybrids with the target polynucleotide of interest. Mutations, insertions, and deletion, can be produced in a given polynucleotide sequence in many ways, by methods currently known to an ordinarily skilled artisan, and perhaps by other methods which may become known in the future.
The potential variations in the probes listed is due, in part, to the redundancy of the genetic code. Because of the redundancy of the genetic code, i.e., more than one coding nucleotide triplet (codon) can be used for most of the amino acids used to make proteins. Therefore different nucleotide sequences can code for a particular amino acid. Thus, the amino acid sequences of the B. thuringiensis δ-endotoxins and peptides can be prepared by equivalent nucleotide sequences encoding the same amino acid sequence of the protein or peptide. Accordingly, the subject invention includes such equivalent nucleotide sequences. Also, inverse or complement sequences are an aspect of the subject invention and can be readily used by a person skilled in this art. In addition it has been shown that proteins of identified structure and function may be constructed by changing the amino acid sequence if such changes do not alter the protein secondary structure (Kaiser and Kezdy, 1984). Thus, the subject invention includes mutants of the amino acid sequence depicted herein which do not alter the protein secondary structure, or if the structure is altered, the biological activity is substantially retained. Further, the invention also includes mutants of organisms hosting all or part of a δ-endotoxin encoding a gene of the invention. Such mutants can be made by techniques well known to persons skilled in the art. For example, UV irradiation can be used to prepare mutants of host organisms. Likewise, such mutants may include asporogenous host cells which also can be prepared by procedures well known in the art.
4.15 Ribozymes
Ribozymes are enzymatic RNA molecules which cleave particular mRNA species. In certain embodiments, the inventors contemplate the selection and utilization of ribozymes capable of cleaving the RNA segments of the present invention, and their use to reduce activity of target mRNAs in particular cell types or tissues.
Six basic varieties of naturally-occurring enzymatic RNAs are known presently. Each can catalyze the hydrolysis of RNA phosphodiester bonds in trans (and thus can cleave other RNA molecules) under physiological conditions. In general, enzymatic nucleic acids act by first binding to a target RNA. Such binding occurs through the target binding portion of a enzymatic nucleic acid which is held in close proximity to an enzymatic portion of the molecule that acts to cleave the target RNA. Thus, the enzymatic nucleic acid first recognizes and then binds a target RNA through complementary base-pairing, and once bound to the correct site, acts enzymatically to cut the target RNA. Strategic cleavage of such a target RNA will destroy its ability to direct synthesis of an encoded protein. After an enzymatic nucleic acid has bound and cleaved its RNA target, it is released from that RNA to search for another target and can repeatedly bind and cleave new targets.
The enzymatic nature of a ribozyme is advantageous over many technologies, such as antisense technology (where a nucleic acid molecule simply binds to a nucleic acid target to block its translation) since the concentration of ribozyme necessary to affect a therapeutic treatment is lower than that of an antisense oligonucleotide. This advantage reflects the ability of the ribozyme to act enzymatically. Thus, a single ribozyme molecule is able to cleave many molecules of target RNA. In addition, the ribozyme is a highly specific inhibitor, with the specificity of inhibition depending not only on the base pairing mechanism of binding to the target RNA, but also on the mechanism of target RNA cleavage. Single mismatches, or base-substitutions, near the site of cleavage can completely eliminate catalytic activity of a ribozyme. Similar mismatches in antisense molecules do not prevent their action (Woolf et al., 1992). Thus, the specificity of action of a ribozyme is greater than that of an antisense oligonucleotide binding the same RNA site.
The enzymatic nucleic acid molecule may be formed in a hammerhead, hairpin, a hepatitis δ virus, group I intron or RNaseP RNA (in association with an RNA guide sequence) or Neurospora VS RNA motif. Examples of hammerhead motifs are described by Rossi et al. (1992); examples of hairpin motifs are described by Hampel et al. (Eur. Pat. EP 0360257), Hampel and Tritz (1989), Hampel et al. (1990) and Cech et al. (U.S. Pat. No. 5,631,359; an example of the hepatitis δ virus motif is described by Perrotta and Been (1992); an example of the RNaseP motif is described by Guerrier-Takada et al. (1983); Neurospora VS RNA ribozyme motif is described by Collins (Saville and Collins, 1990; Saville and Collins, 1991; Collins and Olive, 1993); and an example of the Group I intron is described by Cech et al. (U.S. Pat. No. 4,987,071). All that is important in an enzymatic nucleic acid molecule of this invention is that it has a specific substrate binding site which is complementary to one or more of the target gene RNA regions, and that it have nucleotide sequences within or surrounding that substrate binding site which impart an RNA cleaving activity to the molecule. Thus the ribozyme constructs need not be limited to specific motifs mentioned herein.
The invention provides a method for producing a class of enzymatic cleaving agents which exhibit a high degree of specificity for the RNA of a desired target. The enzymatic nucleic acid molecule is preferably targeted to a highly conserved sequence region of a target mRNA such that specific treatment of a disease or condition can be provided with either one or several enzymatic nucleic acids. Such enzymatic nucleic acid molecules can be delivered exogenously to specific cells as required. Alternatively, the ribozymes can be expressed from DNA or RNA vectors that are delivered to specific cells.
Small enzymatic nucleic acid motifs (e.g., of the hammerhead or the hairpin structure) may be used for exogenous delivery. The simple structure of these molecules increases the ability of the enzymatic nucleic acid to invade targeted regions of the mRNA structure. Alternatively, catalytic RNA molecules can be expressed within cells from eukaryotic promoters (e.g., Scanlon et al., 1991; Kashani-Sabet et al., 1992; Dropulic et al., 1992; Weerasinghe et al., 1991; Ojwang et al., 1992; Chen et al., 1992; Sarver et al., 1990). Those skilled in the art realize that any ribozyme can be expressed in eukaryotic cells from the appropriate DNA vector. The activity of such ribozymes can be augmented by their release from the primary transcript by a second ribozyme (Draper et al., Int. Pat. Appl. Publ. No. WO 93/23569, and Sullivan et al., Int. Pat. Appl. Publ. No. WO 94/02595, both hereby incorporated in their totality by reference herein; Ohkawa et al., 1992; Taira et al., 1991; Ventura et al., 1993).
Ribozymes may be added directly, or can be complexed with cationic lipids, lipid complexes, packaged within liposomes, or otherwise delivered to target cells. The RNA or RNA complexes can be locally administered to relevant tissues ex viva, or in vivo through injection, aerosol inhalation, infusion pump or stent, with or without their incorporation in biopolymers.
Ribozymes may be designed as described in Draper et al. (Int. Pat. Appl. Publ. No. WO 93/23569), or Sullivan et al., (Int. Pat. Appl. Publ. No. WO 94/02595) and synthesized to be tested in vitro and in viva, as described. Such ribozymes can also be optimized for delivery. While specific examples are provided, those in the art will recognize that equivalent RNA targets in other species can be utilized when necessary.
Hammerhead or hairpin ribozymes may be individually analyzed by computer folding (Jaeger et al., 1989) to assess whether the ribozyme sequences fold into the appropriate secondary structure. Those ribozymes with unfavorable intramolecular interactions between the binding arms and the catalytic core are eliminated from consideration. Varying binding arm lengths can be chosen to optimize activity. Generally, at least 5 bases on each arm are able to bind to, or otherwise interact with, the target RNA.
Ribozymes of the hammerhead or hairpin motif may be designed to anneal to various sites in the mRNA message, and can be chemically synthesized. The method of synthesis used follows the procedure for normal RNA synthesis as described in Usman et al. (1987) and in Scaringe et al. (1990) and makes use of common nucleic acid protecting and coupling groups, such as dimethoxytrityl at the 5′-end, and phosphoramidites at the 3′-end. Average stepwise coupling yields are typically >98%. Hairpin ribozymes may be synthesized in two parts and annealed to reconstruct an active ribozyme (Chowrira and Burke, 1992). Ribozymes may be modified extensively to enhance stability by modification with nuclease resistant groups, for example, 2′-amino, 2′-C-allyl, 2′-fluoro, 2′-o-methyl, 2′-H (for a review see Usman and Cedergren, 1992). Ribozymes may be purified by gel electrophoresis using general methods or by high pressure liquid chromatography and resuspended in water.
Ribozyme activity can be optimized by altering the length of the ribozyme binding arms, or chemically synthesizing ribozymes with modifications that prevent their degradation by serum ribonucleases (see e.g., Int. Pat. Appl. Publ. No. WO 92/07065; Perrault et al, 1990; Pieken et al., 1991; Usman and Cedergren, 1992; Int. Pat. Appl. Publ. No. WO 93/15187; Int. Pat. Appl. Publ. No. WO 91/03162; Eur. Pat. Appl. Publ. No. 92110298.4; U.S. Pat. No. 5,334,711; and Int. Pat. Appl. Publ. No. WO 94/13688, which describe various chemical modifications that can be made to the sugar moieties of enzymatic RNA molecules), modifications which enhance their efficacy in cells, and removal of stem II bases to shorten RNA synthesis times and reduce chemical requirements.
Sullivan et al. (Int. Pat. Appl. Publ. No. WO 94/02595) describes the general methods for delivery of enzymatic RNA molecules. Ribozymes may be administered to cells by a variety of methods known to those familiar to the art, including, but not restricted to, encapsulation in liposomes, by iontophoresis, or by incorporation into other vehicles, such as hydrogels, cyclodextrins, biodegradable nanocapsules, and bioadhesive microspheres. For some indications, ribozymes may be directly delivered ex vivo to cells or tissues with or without the aforementioned vehicles. Alternatively, the RNA/vehicle combination may be locally delivered by direct inhalation, by direct injection or by use of a catheter, infusion pump or stent. Other routes of delivery include, but are not limited to, intravascular, intramuscular, subcutaneous or joint injection, aerosol inhalation, oral (tablet or pill form), topical, systemic, ocular, intraperitoneal and/or intrathecal delivery. More detailed descriptions of ribozyme delivery and administration are provided in Sullivan et al. (Int. Pat. Appl. Publ. No. WO 94/02595) and Draper et al. (Int. Pat. Appl. Publ. No. WO 93/23569) which have been incorporated by reference herein.
Another means of accumulating high concentrations of a ribozyme(s) within cells is to incorporate the ribozyme-encoding sequences into a DNA expression vector. Transcription of the ribozyme sequences are driven from a promoter for eukaryotic RNA polymerase I (pol I), RNA polymerase II (pol II), or RNA polymerase III (pol III). Transcripts from pol II or pol III promoters will be expressed at high levels in all cells; the levels of a given pol II promoter in a given cell type will depend on the nature of the gene regulatory sequences (enhancers, silencers, etc.) present nearby. Prokaryotic RNA polymerase promoters may also be used, providing that the prokaryotic RNA polymerase enzyme is expressed in the appropriate cells (Elroy-Stein and Moss, 1990; Gao and Huang, 1993; Lieber et al., 1993; Zhou et at, 1990). Ribozymes expressed from such promoters can function in mammalian cells (e.g. Kashani-Saber et al., 1992; Ojwang et al., 1992; Chen et al., 1992; Yu et al., 1993; L'Huillier et al., 1992; Lisziewicz et al., 1993). Such transcription units can be incorporated into a variety of vectors for introduction into mammalian cells, including but not restricted to, plasmid DNA vectors, viral DNA vectors (such as adenovirus or adeno-associated vectors), or viral RNA vectors (such as retroviral, semliki forest virus, sindbis virus vectors).
Ribozymes of this invention may be used as diagnostic tools to examine genetic drift and mutations within cell lines or cell types. They can also be used to assess levels of the target RNA molecule. The close relationship between ribozyme activity and the structure of the target RNA allows the detection of mutations in any region of the molecule which alters the base-pairing and three-dimensional structure of the target RNA. By using multiple ribozymes described in this invention, one may map nucleotide changes which are important to RNA structure and function in vitro, as well as in cells and tissues. Cleavage of target RNAs with ribozymes may be used to inhibit gene expression and define the role (essentially) of specified gene products in particular cells or cell types.
5.0 EXAMPLES
The following examples are included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.
5.1 Example 1
Three-Dimensional Structure of Cry3Bb
The three-dimensional structure of Cry3Bb was determined by X-ray crystallography. Crystallization of Cry3Bb and X-ray diffraction data collection were performed as described by Cody et al. (1992). The crystal structure of Cry3Bb was refined to a residual R factor of 18.0% using data collected to 2.4 Å resolution. The crystals belong to the space group C2221 with unit cell dimensions a=122.44, b=131.81, and c=105.37 Å and contain one molecule in the asymmetric unit. Atomic coordinates for Cry3Bb are described in Example 31 and listed in Section 9.
The structure of Cry3Bb is similar to that of Cry3A (Li et al., 1991). It consists of 5825 protein atoms from 588 residues (amino acids 64-652) forming three discrete domains (FIG. 1). A total of 251 water molecules have been identified in the Cry3Bb structure (FIG. 2). Domain 1 (residues 64-294) is a seven helical bundle formed by six helices twisted around the central helix, α5 (FIG. 3). The amino acids forming each helix are listed in FIG. 4. Domain 2 (residues 295-502) contains three antiparallel O-sheets (FIG. 5A and FIG. 5B). Sheets 1 and 2, each composed of 4 β strands, form the distinctive “Greek key” motif. The outer surface of sheet 3, composed of 3 β strands, makes contact with helix α7 of domain 1. FIG. 6 lists the amino acids comprising each β strand in domain 2. A small α helix, α8 which follows β strand 1, is also included in domain 2. Domain 3 (residues 503-652) has a “jelly roll” β-barrel topology which has a hydrophobic core and is nearly parallel to the α and perpendicular to the c axes of the lattice (FIG. 7A and FIG. 7B). The amino acids comprising each β strand of domain 3 are listed in FIG. 8.
The monomers of Cry3Bb in the crystal form a dimeric quaternary structure along a two-fold axis parallel to the α axis (FIG. 9A and FIG. 9B). Helix α6 lies in a cleft formed by the interface of domain 1 and domains 1 and 3 of its symmetry related molecule. There are numerous close hydrogen bonding contacts along this surface, confirming the structural stability of the dimer.
5.2 Example 2
Preparation of Cry3B.60
B. thuringiensis EG7231 was grown through sporulation in C2 medium with chloramphenicol (Cml) selection. The solids from this culture were recovered by centrifugation and washed with water. The toxin was purified by recrystallization from 4.0 M NaBr (Cody et al., 1992). The purified Cry3Bb was solubilized in 10 ml of 50 mM KOH/100 mg Cry3Bb and buffered to pH 9.0 with 100 mM CAPS (pH 9.0). The soluble toxin was treated with trypsin at a weight ratio of 50 mg toxin to 1 mg trypsin. After 20 min of trypsin digestion the predominant protein visualized by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) was 60 kDa. Further digestion of the 60-kDa toxin was not observed. FIG. 4 illustrates the Coomassie-stained Cry3Bb and Cry3Bb.60 following SDS-PAGE.
5.3 Example 3
Purification and Sequencing of Cry3Bb.60
Cry3Bb.60 was electrophoretically purified by SDS-PAGE and electroblotted to Immobilon-P® (Millipore) membrane by semi-dry transfer at 15V for 30 min. The membrane was then washed twice with water and stained with 0.025% R-250, 40% methanol. To reduce the background, the blot was destained with 50% methanol until the stained protein bands were visible. The blot was then air dried, and the stained Cry3Bb.60 band was cut out of the membrane. This band was sent to the Tufts University Sequencing Laboratory (Boston, Mass.) for N-terminal sequencing. The experimentally-determined N-terminal amino acid sequence is shown in Table 7 beside the known amino acid sequence starting at amino acid residue 160.







TABLE 7







AMINO ACID SEQUENCE OF THE N-TERMINUS OF CRY3BB.60


AND COMPARISON TO THE KNOWN SEQUENCE OF CRY3BB









Deduced Sequence
Known Sequence
Residue #





S
S
160


K
K
161


R
R
162


S
S
163


Q
Q
164


D
D
165


R
R
166









5.4 Example 4
Bioactivity of Cry3Bb.60
Cry3Bb was prepared for bioassay by solubilization in a minimal amount of 50 mM KOH, 10 ml per 100 mg toxin, and buffered to pH 9.0 with 100 mM CAPS, pH 9.0. Cry3Bb.60 was prepared as described in Example 1. Both preparations were kept at room temperature 12 to 16 hours prior to bioassay. After seven days the mortality of the population was determined and analyzed to determine the lethal concentration of each toxin. These results are numerized in Table 8.







TABLE 8







BIOACTIVITY OF CRY3BB AND CRY3BB.60 AGAINST


THE SOUTHERN CORN ROOTWORM


(DIABIOTICA UNDECIMPUNCTATA)










LC50 mg/well
95% C.I.














Cry3Bb
24.09
15-39



Cry3Bb.60
6.72
5.25-8.4 









5.5 Example 5
Ion-Channel Formation by Cry3Bb and CryB2.60
Cry3Bb.60 and Cry3Bb were evaluated for their ability to form ion channels in planar lipid bilayers. Bilayers of phosphatidylcholine were formed on Teflon® supports over a 0.7-mm hole. A bathing solution of 3.5 ml 100 mM KOH, 10 mM CaCl2, 100 mM CAPS (pH 9.5) was placed on either side of the Teflon® partition. The toxin was added to one side of the partition and a voltage of 60 mV was imposed across the phosphatidylcholine bilayer. Any leakage of ions through the membrane was amplified and recorded. An analysis of the frequency of the conductances created by either Cry3Bb or Cry3Bb.60 are illustrated in FIG. 5A and FIG. 5B. Cry3Bb.60 readily formed ion channels whereas Cry3Bb rarely formed channels.
5.6 Example 6
Formation of High Molecular-Weight Oligomers
Individual molecules of Cry3Bb or Cry3Bb.60 form a complex with another like molecule. The ability of Cry3Bb to form an oligomer is not reproducibly apparent. The complex cannot be repeatedly observed to form under nondenaturing conditions. Cry3Bb.60 formed a significantly greater amount of a higher molecular-weight complex (≧120 kDa) with other Cry3Bb.60 molecules. Oligomers of Cry3Bb are demonstrated by the intensity of the Coomassie-stained SDS polyacrylamide gel. Oligomerization is visualized on SDS-PAGE by not heating samples prior to loading on the gel to retain some nondenatured toxin. These data suggest that Cry3Bb.60 more readily forms the higher order complex than Cry3Bb alone. Oligomerization is also observed by studying the conductance produced by these molecules and the time-dependent increase in conductance. This change in conductance can be attributed to oligomerization of the toxin.
5.7 Example 7
Design Method 1: Identification and Alteration of Protease-Sensitive Sites and Proteolytic Processing
It has been reported in the literature that treatment of Cry3A toxin protein with trypsin, an enzyme that cleaves proteins on the carboxyl side of available lysine and arginine residues, yields a stable cleavage product of 55 kDa from the 67 kDa native protein (Carroll et al., 1989). N-terminal sequencing of the 55 kDa product showed cleavage occurs at amino acid residue R158. The truncated Cry3A protein was found to retain the same level of insecticidal activity as the native protein. Cry3Bb toxin protein was also treated with trypsin. After digestion, the protein size decreased from 68 kDa, the molecular weight of the native Cry3Bb toxin, to 60 kDa. No further digestion was observed. N-terminal sequencing revealed the trypsin cleavage site of the truncated toxin (Cry3Bb.60) to be amino acid R159 in lα3,4 of Cry3Bb. Unexpectedly, the bioactivity of the truncated Cry3Bb toxin was found to increase.
Using this method, protease digestion of a B. thuringiensis toxin protein, a proteolytically sensitive site was identified on Cry3Bb, and a more highly active form of the protein (Cry3Bb.60) was identified. Modifications to this proteolytically-sensitive site by introducing an additional protease recognition site also resulted in the isolation of a biologically more active protein. It is also possible that removal of other protease-sensitive site(s) may improve activity. Proteolytically sensitive regions, once identified, may be modified or utilized to produce biologically more active toxins.
5.7.1 Cry3Bb.60
Treatment of solubilized Cry3Bb toxin protein with trypsin results in the isolation of a stable, truncated Cry3Bb toxin protein with a molecular weight of 60 kDa (Cry3Bb.60). N-terminal sequencing of Cry3Bb.60 shows the trypsin-sensitive site to be R159 in lα3,4 of the native toxin. Trypsin digestion results in the removal of helices 1-3 from the native Cry3Bb but also increases the activity of the toxin against SCRW larvae approximately four-fold.
Cry3Bb.60 is a unique toxin with enhanced insecticidal use over the parent Cry3Bb. Improved biological activity, is only one parameter that distinguishes it as a new toxin. Aside from the reduced size, Cry3Bb.60 is also a more soluble protein. Cry313b pre-cipitates from solution at pH 6.5 while Cry3Bb.60 remains in solution from pH 4.5 to pH 12. Cry3Bb.60 also forms ion channels with greater frequency than Cry3Bb.
Cry3Bb.60 is produced by either the proteolytic removal of the first 159 amino acid residues, or the in vivo production of this toxin, by bacteria or plants expressing the gene for Cry3Bb.60, that is, the Cry3Bb gene without the first 483 nucleotides.
In conclusion, Cry3Bb.60 is distinct from Cry3Bb in several important ways: enhanced insecticidal activity; enhanced range of solubility; enhanced ability to form channels; and reduced size.
5.7.2 EG11221
Semi-random mutagenesis of the trypsin-sensitive lα3,4 region of Cry3Bb resulted in the isolation of Cry3Bb.11221, a designed Cry3Bb protein that exhibits over a 6-fold increase in activity against SCRW larvae compared to WT. Cry3Bb.11221 has 4 amino acid changes in the lα3,4 region. One of these changes, L158R, introduces an additional trypsin site adjacent to R159, the proteolytically sensitive site used to produce Cry3Bb.60 (example 4.1.1). Cry3Bb.11221 is produced by B. thuringiensis as a full length toxin protein but is presumably digested by insect gut proteases to the same size as Cry3Bb.60 (see Cry3A results from Carroll et al., 1989). The additional protease recognition site may make the lα3,4 region even more sensitive to digestion, thereby increasing activity.
5.8 Example 8
Design Method 2: Determination and Manipulation of Bound Water
There are several ways that water molecules can associate with a protein, including surface water that is easily removed and bound water that is more difficult to extract (Dunitz, 1994; Zhang and Matthews, 1994). The function of bound water has been the subject of significant academic extrapolation, but the precise function has little experimental validation. Some of the most interesting bound or structural water is the water that participates in the protein structure from inside the protein itself.
The occupation of a site by a water molecule can indicate a stable pocket within a protein or a looseness of packing created by water-mediated salt bridges and hydrogen bonding to water. This can reduce the degree of bonding between amino acids, possibly making the region more flexible. A different amino acid sequence around that same site could result in better packing, collapsing the pocket around polar or charged amino acids. This may result in decreased flexibility. Therefore, the degree of hydration of a region of a protein may determine the flexibility or mobility of that region, and manipulation of the hydration may alter the flexibility. Methods of increasing the hydration of a water-exposed region include increasing the number of hydrophobic residues along that surface. It is taught in the art that exposed hydrophobic residues require significantly more water to hydrate than hydrophilic residues (CRC Handbook of Chemistry and Physics, CRC Press, Inc.). It is not taught, however, that by doing this, improvements to the biological activity of a protein can be achieved.
Structural water has not previously been identified in B. thuringiensis δ-endotoxins including Cry3Bb. Furthermore, there are no reports of the function of this structural water in δ-endotoxins or bacterial toxins. In the analysis of Cry3Bb, it was observed that a collection of water molecules are located around lα3,4, a site defined by the inventors as important for improvement of bioactivity. The loop α3,4 region is surface exposed and may define a hinge in the protein permitting either removal or movement of the first three helices of domain 1. The hydration found around this region may impart flexibility and mobility to this loop. The observation of structural water at the lα3,4 site provided an analytical tool for further structure analysis. If this important site is surrounded by water, then other important sites may also be completely or partially surrounded by water. Using this insight, structural water surrounding helices 5 and 6 was then identified. This structural water forms a column through the protein, effectively separating helices 5 and 6 from the rest of the molecule. The structures of Cry3A and Cry3Bb suggest that helices 5 and 6 are tightly associated, bound together by Van der Waals interactions. Alone, helix 5 from Cry3A, although insufficient for biological activity, has been demonstrated to have the ability to form ion channels in an artificial membrane (Gazit and Shai, 1993). The ion channels formed by helix 5 are 10-fold smaller than the channels of the full length toxin suggesting that significantly more toxin structure is required for the full-sized ion channels. In Cry3Bb, helix 5 as part of a cluster of α helices (domain 1) has been found to form ion channels (Von Tersch et al., 1994). Unpublished experimental observations by the inventors demonstrate that helix 6 also crossed the biological membrane. Helices 5 and 6, therefore, are the putative channel-forming helices necessary for toxicity.
The hydration around these helices may indicate that flexibility of this region is necessary for toxicity. It is conceivable, therefore, that if it were possible to improve the hydration around helices 5 and 6, one could create a better toxin protein. Care must be taken, however, to avoid creating continuous hydrophobic surfaces between helices 5-6 and any other part of the protein which could, by hydrophobic interactions, act to restrict movement of the mobile helices. The mobility of helices 5 and 6 may also depend on the flexibility of the loops attached to them as well as on other regions of the Cry3Bb molecule, particularly in domain 1, which may undergo conformational changes to allow insertion of the 2 helices into the membrane. Altering the hydration of these regions of the protein may also affect its bioactivity.
5.8.1 Cry3Bb.11032
A collection of bound water residues indicated the relative flexibility of the lα3,4 region. The flexibility of this loop can be increased by increasing the hydration of the region by substituting relatively hydrophobic residues for the exposed hydrophilic residues. An example of an improved, designed protein having this type of substitution is Cry3Bb.11032. Cry3Bb.11032 has the amino acid change D165G; glycine is more hydrophobic than aspartate (Kyte and Doolittle hydrophobicity score of −0.4 vs. −3.5 for aspartate). Cry3Bb.11032 is approximately 3 times more active than WT Cry3Bb.
5.8.2 Cry3Bb.11051
To increase the hydration of the lα4,5 region of Cry3Bb, glycine was substituted for the surface exposed residue K189. Glycine is more hydrophobic than lysine (Kyte and Doolittle hydrophobicity score of −0.4 vs. −3.9 for lysine) and may result in an increase in bound water. The increase in bound water may impart greater flexibility to the loop region which precedes the channel-forming helix, α5. The designed Cry3Bb protein with the K189G change, Cry3Bb.11051, exhibits a 3-fold increase in activity compared to WT Cry3Bb.
5.8.3 Alterations to lα7,β1 (Cry3Bb.11241 and 11242)
Amino acid changes made in the surface-exposed loop connecting α-helix 7 and β-strand 1 (lα7,β1) resulted in the identification of 2 altered Cry3Bb proteins with increased bioactivities, Cry3Bb.11241 and Cry3Bb.11242. Analysis of the hydropathy index of 2 of these proteins over the 20 amino acid sequence 281-300, inclusive of the lα7,β1 region, reveal that the amino acid substitutions in these proteins have made the lα7,β1 region much more hydrophobic. The grand average of hydropathy value (GRAVY) was determined for each protein sequence using the PC\GENE® (IntelliGenetics, Inc., Mountain View, Calif., release 6.85) protein sequence analysis computer program, SOAP, and a 7 amino acid interval. The SOAP program is based on the method of Kyte and Doolittle (1982). The increase in hydrophobicity of the lα7,β3 region for each protein may increase the hydration of the loop and, therefore, the flexibility. The altered proteins, their respective amino acid changes, fold-increases over WT bioactivity, and GRAVY values are listed in Table 9.







TABLE 9







HYDROPATHY VALUES FOR THE Lα7, β1 REGION OF


CRY3BB AND 2 DESIGNED CRY3BB PROTEINS SHOWING


INCREASED SCRW BIOACTIVITY












Fold Increase in
GRAVY


Cry3Bb*
Amino Acid
Bioactivity Over
(Amino Acids


Protein
Changes
WT
281-300)













wildtype
—
—
4.50


Cry3Bb.11241
Y287F, D288N,
2.6×
10.70



R290L




Cry3Bb.11242
R290V
2.5×
8.85









5.8.4 Alterations to lβ1,α8 (Cry3Bb.11228, Cry3Bb.11229, Cry3Bb.11230, Cry3Bb.11233, Cry3Bb.11236, Cry3Bb.11237, Cry3Bb.11238 and Cry3Bb.11239)

The surface-exposed loop between β-strand 1 and α-helix 8 (lβ3,α8) defines the boundary between domains 1 and 2 of Cry3Bb. The introduction of semi-random amino acid changes to this region resulted in the identification of several altered Cry3Bb proteins with increased bioactivity. Hydropathy index analysis of the amino acid substitutions found in the altered proteins shows that the changes have made the exposed region more hydrophobic which may result in increased hydration and flexibility. Table 10 lists the altered proteins, their respective amino acid changes and fold increases over WT Cry3Bb and the grand average of hydropathy value (GRAVY) determined using the PC\GENE® (IntelliGenetics, Inc., Mountain View, Calif., release 6.85) protein sequence analysis program, SOAP, over the 20 amino acid sequence 305-324 inclusive of lβ1,α8, using a 7 amino acid interval.







TABLE 10







HYDROPATHY VALUES FOR Lβ1,α8 REGION OF CRY3BB


AND DESIGNED CRY3BB* PROTEINS SHOWING 


INCREASED SCRW BIOACTIVITY












Fold Increase in
GRAVY


Cry3Bb*
Amino Acid
Bioactivity Over
(Amino Acids


Protein
Changes
Wild Type
305-324)





wildtype
—
—
0.85


Cry3Bb.11228
S311L, N313T,
4.1×
4.35



E317K




Cry3Bb.11229
S311T, E317K,
2.5×
2.60



Y318C




Cry3Bb.11230
S311A, L312V,
4.7×
3.65



Q316W




Cry3Bb.11233
S311A, Q316D
2.2×
2.15


Cry3Bb.11236
S311I
3.1×
3.50


Cry3Bb.11237
S311I, N313H
5.4×
3.65


Cry3Bb.11238
N313V, T314N,
2.6×
9.85



Q316M, E317V




Cry3Bb.11239
N313R, L315P,
2.8×
3.95



Q316L, E317A









5.8.5 Cry3Bb.11227, Cry3Bb.11241 and Cry3Bb.11242

Amino acid Q238, located in helix 6 of Cry3Bb, has been identified as a residue that, by its large size and hydrogen bonding to R290, blocks complete hydration of the space between helix 6 and helix 4. Substitution of R290 with amino acids that do not form hydrogen bonds or that have side chains that can not span the physical distance to hydrogen bond with Q238 may result in increased hydration around Q238. Q238, unable to hydrogen bond to R290, may now bind water. This may increase the flexibility of the channel-forming region. Designed proteins Cry3Bb.11227 (R290N), Cry3Bb.11241 (R290L) and Cry3Bb.11242 (R290V) show increased activities of approximately 2-fold, 2.6-fold and 2.5-fold, respectively, against SCRW larvae compared to WT.
5.9 Example 9
Design Method 3: Manipulation of Hydrogen Bonds Around Mobile Regions
Mobility of regions of a protein may be required for activity. The mobility of the α5,6 region, the putative channel-forming region of Cry3Bb, may be improved by decreasing the number of hydrogen bonds, including salt bridges (hydrogen bonds between oppositely charged amino acid side chains), between helices 5-6 and any other part of the molecule or dimer structure. These hydrogen bonds may impede the movement of the two helices. Decreasing the number of hydrogen bonds and salt bridges may improve biological activity. Replacement of hydrogen-bonding amino acids with hydrophobic residues must be done with caution to avoid creating continuous hydrophobic surfaces between helices 5-6 and any other part of the dimer. This may decrease mobility by increasing hydrophobic surface interactions.
5.9.1 Cry3Bb.11222 And Cry3Bb.11223
Tyr230 is located on helix 6 and, in the quaternary dimer structure of Cry3Bb, this amino acid is coordinated with Tyr230 from the adjacent molecule. Three hydrogen bonds are formed between the two helices 6 in the two monomers because of this single amino acid. In order to improve the flexibility of helices 5-6, the helices theoretically capable of penetrating the membrane and forming an ion channel, the hydrogen bonds across the dimer were removed by changing this amino acid and a corresponding increase in biological activity was observed. The designed Cry3Bb proteins, Cry3Bb.11222 and Cry3Bb.EG11223, show a 4-fold and 2.8-fold increase in SCRW activity, respectively, compared to WT.
5.9.2 Cry3Bb.11051
Designed Cry3Bb protein Cry3Bb.11051 has amino acid change K189G in lα4,5 of domain 1. In the WT Cry3Bb structure, the exposed side chain of K189 is close enough to the exposed side change of E123, located in lα2b,3, to form hydrogen bonds. Substitution of K189 with glycine, as found in this position in Cry3A, removes the possibility of hydrogen bond formation at this site and results in a protein with a bioactivity three-fold greater than WT Cry3Bb.
5.9.3 Cry3Bb.11227, Cry3Bb.11241 and Cry3Bb.11242
Amino acid Q238, located in helix 6 of Cry3Bb, has been identified as a residue that, by its large size and hydrogen bonding to R290, blocks complete hydration of the space between helix 6 and helix 4. Substitution of R290 with amino acids that do not form hydrogen bonds or that have side chains that can not span the physical distance to hydrogen bond with Q238 may increase the flexibility of the channel-forming region. Designed proteins Cry3Bb.11227 (R290N), Cry3Bb.11241 (R290L) and Cry3Bb.11242 (R290V) show increased activities of approximately 2-fold, 2.6-fold and 2.5-fold, respectively, against SCRW larvae compared to WT
5.10 Example 10
Design Method 4: Loop Analysis and Loop Design Around Flexible Helices
Loop regions of a protein structure may be involved in numerous functions of the protein including, but not limited to, channel formation, quaternary structure formation and maintenance, and receptor binding. Cry3Bb is a channel-forming protein. The availability of the ion channel-forming helices of δ-endotoxins to move into the bilayer depend upon the absence of forces that hinder the process. One of the forces possibly limiting this process is the steric hindrance of amino acid side chains in loop regions around the critical helices. The literature suggests that in at least one other bacterial toxin, not a B. thuringiensis toxin, the toxin molecule opens up or, in scientific terms, loses some of the quaternary structure to expose a membrane-active region (Cramer et al., 1990). This literature does not teach how to improve the probability of this event occurring and it is not known if B. thuringiensis toxins use this same process to penetrate the membrane. Reducing the steric hindrance of the amino acid side chains in these critical regions by reducing size or altering side chain positioning with the corresponding increase in biological activity was the inventive step.
5.10.1 Analysis of the Loop Between Helices 3 and 4 (Cry3Bb.11032)
The inventors have discovered that the first three helices of domain one could be cleaved from the rest of the toxin by proteolytic digestion of the loop between helices α3 and α4 (Cry3Bb.60). Initial efforts to truncate the cry3Bb gene to produce this shortened, though more active Cry3Bb molecule, failed. For unknown reasons, B. thuringiensis failed to synthesize this 60-kDa molecule. It was then reasoned that perhaps the first three helices of domain 1 did not have to be proteolytically removed, or equivalently, the protein did not have to be synthesized in this truncated form to take advantage of the Cry3Bb.60 design. It was observed that the protein Cry3A had a small amino acid near the lα3,4 that might impart greater flexibility in the loop region thereby permitting the first three helices of domain 1 to move out of the way, exposing the membrane-active region. By designing a Cry3Bb molecule with a glycine residue near this loop, the steric hindrance of residues in the loop might be lessened. The redesigned protein, Cry3Bb.11032, has the amino acid change D165G, which replaces the larger aspartate residue (average mass of 115.09) with the smallest amino acid, glycine (average mass of 57.05). The activity of Cry3Bb.11032 is approximately 3-fold greater than that of the WT protein. In this way, the loop between helices α3 and α4 was rationally redesigned with a corresponding increase in the biological activity.
5.10.2 Cry3Bb.11051
The loop region connecting helices α4 and α5 in Cry3Bb must be flexible so that the channel-forming helices α5-α6 can penetrate into the membrane. It was noticed that Cry3A has a glycine residue in the middle of this loop that may impart greater flexibility. The corresponding change, K189G, was made in Cry3Bb and the resulting, designed protein, Cry3Bb.11051, exhibits a 3-fold increase in activity against SCRW larvae compare to WT Cry3Bb.
5.10.3 Analysis of the Loop Between β-Strand 1 and Helix 8 (Cry3Bb.11228, Cry3Bb.11229, Cry3Bb.11230, Cry3Bb.11232, Cry3Bb.11233, Cry3Bb.11236, Cry3Bb.11237, Cry3Bb.11238, and Cry3Bb.11239)
The loop region located between β strand 1 of domain 2 and α helix 8 in domain 2 is very close to the loop between α helices 6 and 7 in domain 1. Some of the amino acids side chains of lβ1,α8 appear as though they may sterically impede movement of lα6,7. Since lα6,7 must be flexible for the channel-forming helices α5-α6 to insert into the membrane, it was thought that re-engineering this loop may change the positioning of the side chains resulting in less steric hindrance. This was accomplished creating proteins with increased biological activities ranging from 2.2 to 5.4 times greater than WT. These designed toxin proteins and their amino acid changes are listed in Table 2 as Cry3Bb.11228, Cry3Bb.11229, Cry3Bb.11230, Cry3Bb.11232, Cry3Bb.11233, Cry3 Bb.11236, Cry3Bb.11237, Cry3Bb.11238, and Cry3Bb.11239.
5.10.4 Analysis of the Loop Between Helix 7 and β-Strand 1 (Cry3Bb.1227, Cry3Bb.11234, Cry3Bb.11241, Cry3Bb.11242, and Cry3Bb.11036)
If Cry3Bb is similar to a bacterial toxin which must open up to expose a membrane active region for toxicity, it is possible that other helices in addition to the channel-forming helices must also change positions. It was reasoned that, if helices α5-α6 insert into the membrane, than helix α7 may have to change positions also. It was shown in example 4.4.3 that increasing flexibility between helix α6 and α7 can increase activity, greater flexibility in the loop following helix α7, lα7,β1 may also increase bioactivity. Alterations to the lα7,β1 region of Cry3Bb resulted in the isolation of several proteins with increased activities ranging from 1.9 to 4.3 times greater than WT. These designed proteins are listed in Table 7 as Cry3Bb.11227, Cry3Bb.11234, Cry3Bb.11241, Cry3Bb.11242, and Cry3Bb.11036.
5.11 Example 11
Design Method 5: Loop Design Around β Strands and β Sheets
Loop regions of a protein structure may be involved in numerous functions of the protein including, but not limited to, channel formation, quaternary structure formation and maintenance, and receptor binding. A binding surface is often defined by a number of loops, as is the case with immunoglobulin G (IgG) (see Branden and Tooze, 1991, for review). What can not be determined at this point, however, is what loops will be important for receptor interactions just by looking at the structure of the protein in question. Since a receptor has not been identified for Cry3Bb, it is not even possible to compare the structure of Cry3Bb with other proteins that have the same receptor for structural similarities. To identify Cry3Bb loops that contribute to receptor interactions, random mutagenesis was performed on surface-exposed loops.
As each loop was altered, the profile of the overall bioactivities of the resultant proteins were examined and compared. The loops, especially in domain 2 which appears to be unnecessary for channel activity, fall into two categories: (1) loops that could be altered without much change in the level of bioactivity of the resultant proteins and (2) loops where alterations resulted in overall loss of resultant protein bioactivity. Using this design method, it is possible to identify several loops important for activity.
5.11.1 Analysis of Loop β 2,3
Semi-random mutagenesis of the loop region between β strands 2 and 3 resulted in the production of structurally stable toxin proteins with significantly reduced activities against SCRW larvae. The lβ2,3 region is highly sensitive to amino acid changes indicating that specific amino acids or amino acid sequences are necessary for toxin protein activity. It is conceivable, therefore, that specific changes in the lβ2,3 region will increase the binding and, therefore, the activity of the redesigned toxin protein.
5.11.2 Analysis of Loop β 6,7
Semi-random mutations introduced to the loop region between β strands 6 and 7 resulted in structurally stable proteins with an overall loss of SCRW bioactivity. The lβ6,7 region is highly sensitive to amino acid changes indicating that specific amino acids or amino acid sequences are necessary for toxin protein activity. It is conceivable, therefore, that specific changes in the lβ6,7 region will increase the binding and, therefore, the activity of the redesigned toxin protein.
5.11.3 Analysis of Loop β 10,11
Random mutations to the loop region between β strands 10 and 11 resulted in proteins having an overall loss of SCRW bioactivity. Loop β10,11 is structurally close to and interacts with loops β2,3 and β6,7. Specific changes to individual residues within the lβ10,11 region may also result in increased interaction with the insect membrane, increasing the bioactivity of the toxin protein.
5.11.4 Cry3Bb.11095
Loops β2,3, β6,7 and β10,11 have been identified as important for bioactivity of Cry3Bb. The 3 loops are surface-exposed and structurally close together. Amino acid Q348 in the WT structure, located in β-strand 2 just prior to lβ2,3, does not form any intramolecular contacts. However, replacing Q348 with arginine (Q348R) results in the formation of 2 new hydrogen-bonds between R348 and the backbone carbonyls of R487 and R488, both located in lβ10,11. The new hydrogen bonds may act to stabilize the structure formed by the 3 loops. The designed protein carrying this change, Cry3Bb.11095, is 4.6-fold more active than WT Cry3Bb.
5.12 Example 12
Design Method 6: Identification and Re-Design of Complex Electrostatic Surfaces
Interactions of proteins include hydrophobic interactions (e.g., Van der Waals forces), hydrophilic interactions, including those between opposing charges on amino acid side chains (salt bridges), and hydrogen bonding. Very little is known about δ-endotoxin and receptor interactions. Currently, there are no literature reports identifying the types of interactions that predominate between B. thuringiensis toxins and receptors.
Experimentally, however, it is important to increase the strength of the B. thuringiensis toxin-receptor interaction and not permit the precise determination of the chemical interaction to stand in the way of improving it. To accomplish this, the electrostatic surface of Cry3Bb was defined by solving the Poisson-Boltzman distribution around the molecule. Once this electrically defined surface was solved, it could then be inspected for regions of greatest diversity. It was reasoned that these electrostatically diverse regions would have the greatest probability of participating in the specific interactions between the B. thuringiensis toxin proteins and the receptor, rather than more general and non-specific interactions. Therefore, these regions were chosen for redesign, continuing to increase the electrostatic diversity of the regions. In addition, examination of the electrostatic interaction around the putative channel forming region of the toxin created insights for redesign. This includes identification of an electropositive residue in an otherwise negatively charged conduit (see example 4.6.1).
5.12.1 R290 (Cry3Bb.11227, Cry3Bb.11241, and Cry3Bb.11242)
Examination of the Cry3Bb dimer interface along the domain 1 axis suggested that a pore or conduit for cations might be formed between the monomers. Electrostatic examination of this axis lent additional credibility to this suggestion. In fact, the hypothetical conduit is primarily negatively charged, an observation consistent with the biophysical analysis of cation-selective, δ-endotoxin channels. If a cation channel were formed along the axis of the dimer, then the cation could move between the monomers relatively easily with only one significant hurdle. A positively charged arginine residue (R290) lies in the otherwise negatively charged conduit. This residue could impede the cation movement through the channel. Based on this analysis, R290 was changed to uncharged residues. The bioactivity of redesigned proteins Cry3Bb.11227 (R290N), Cry3Bb.11241 (R290L) and Cry3Bb.11242 (R290V) was improved approximately 2-fold, 2.6-fold and 2.5-fold, respectively.
5.12.2 Cry3Bb.60
Trypsin digestion of solubilized Cry3Bb yields a stable, truncated protein with a molecular weight of 60 kDa (Cry3Bb.60). Trypsin digestion occurs on the carboxyl side of residue R159, effectively removing helices 1 through 3 from the native Cry3Bb structure. The cleavage of the first 3 helices exposes an electrostatic surface different than those found in the native structure. The new surface has a combination of hydrophobic, polar and charged characteristics that may play a role in membrane interactions. The bioactivity of Cry3Bb.60 is 3.6-fold greater than that of WT Cry313b.
5.13 Example 13
Design Method 7: Identification and Removal of Metal Binding Sites
The literature teaches that the in vitro behavior of B. thuringiensis toxins can be increased by chelating divalent cations from the experimental system (Crawford and Harvey 1988). It was not known, however, how these divalent cations inhibited the in vitro activity. Crawford and Harvey (1988) demonstrated that the short circuit current across the midgut was more severely inhibited by B. thuringiensis in the presence of EDTA, a chelator of divalent ions, than in the absence of this agent, thus suggesting that this step in the mode of action of B. thuringiensis could be potentiated by removing divalent ions. Similar observations were made using black-lipid membranes and measuring an increase in the current created by the δ-endotoxins in the presence of EDTA to chelate divalent ions. There were at least three possible explanations for these observations. The first explanation could be that the divalent ions are too large to move through a ion channel more suitable for monovalent ions, thereby blocking the channel. Second, the divalent ions may cover the protein in the very general way, thereby buffering the charge interactions required for toxin membrane interaction and limiting ion channel activity. The third possibility is that a specific metal binding site exists on the protein and, when occupied by divalent ions, the performance of the ion channel is impaired. Although the literature could not differentiate the value of one possibility over another, the third possibility led to an analysis of the Cry3Bb structure searching for a specific metal binding site that might alter the probability that a toxin could form an ion channel.
5.13.1H231 (Cry3Bb.11222, Cry3Bb.11224, Cry3Bb.11225, and Cry3Bb.11226)
A putative metal binding site is formed in the Cry3Bb dimer structure by the H231 residues of each monomer. The H231 residues, located in helix α6, lie adjacent to each other and close to the axis of symmetry of the dimer. Removal of this site by replacement of histidine with other amino acids was evaluated by the absence of EDTA-dependent ion channel activity. The bioactivities of the designed toxin proteins, Cry3Bb.11222, Cry3Bb.1224, Cry3Bb.11225 and Cry3Bb.11226, are increased 4-, 5-, 3.6- and 3-fold, respectively, over that of WT Cry3Bb. Their respective amino acid changes are listed in Table 2.
5.14 Example 14
Design Method 8: Alteration of Quaternary Structure
Cry3Bb can exist in solution as a dimer similar to a related protein, Cry3A (Walters et al., 1992). However, the importance of the dimer to biological activity is not known because the toxin as a monomer or as a higher order structure has not been seriously evaluated. It is assumed that specific amino acid residues contribute to the formation and stability of the quaternary structure. Once a contributing residue is identified, alterations can be made to diminish or enhance the effect of that residue thereby affecting the interaction between monomers. Channel activity is a useful way, but by no means the only way, to assess quaternary structure of Cry3Bb and its derivatives. It has been observed that Cry3Bb creates gated conductances in membranes that grow in size with time, ultimately resulting in large pores in the membrane (the channel activity of WT Cry3Bb is described in Section 12.1). It also has been observed that Cry3A forms a more stable dimer than Cry3Bb and co-incidentally forms higher level conductances faster (FIG. 10). This observation led the inventors to propose that oligomerization and ion channel formation (conductance size and speed of channel formation) were related. Based on this observation Cry3Bb was reengineered to make larger and more stable oligomers at a faster rate. It is assumed in this analysis that the rate of ion channel formation and growth mirrors this process. It is also possible that changes in quaternary structure may not affect channel activity alone or at all. Alterations to quaternary structure may also affect receptor interactions, protein processing in the insect gut environment, as well as other aspects of bioactivity unknown.
5.14.1 Cry3Bb.11048
Comparative structural analysis of Cry3A and Cry3Bb led to the identification of structural differences between the two toxins in the ion channel-forming domain; specifically, an insertion of one amino acid between helix 2a and helix 2b in Cry3Bb. Removal of this additional amino acid in Cry3B2, A104, and a D103E substitution, as in Cry3A, resulted in loss of channel gating and the formation of symmetrical pores. Once the pores are formed they remain open and allow a steady conductance ranging from 25-130 pS. This designed protein, Cry3Bb.11048, is 4.3 times more active than WT Cry3Bb against SCRW larvae.
5.14.2 Oligomerization of Cry3Bb.60
Individual molecules of Cry3Bb or Cry3Bb.60 can form a complex with another like molecule. Oligomerization of Cry3Bb is demonstrated by SDS-PAGE, where samples are not heated in sample buffer prior to loading on the gel. The lack of heat treatment allows some nondenatured toxin to remain. Oligomerization is visualized following Coomassie staining by the appearance of a band at 2 times the molecular weight of the monomer. The intensity of the higher molecular weight band reflects the degree of oligomerization. The ability of Cry3Bb to form an oligomer is not reproducibly apparent. The complex cannot be repeatedly observed to form. Cry3Bb.60, however, forms a significantly greater amount of a higher molecular weight complex (120 kDa). These data suggest that Cry3Bb.60 more readily forms the higher order complex than Cry3Bb alone. Cry3Bb.60 also forms ion channels with greater frequency than WT Cry3Bb (see Section 5.12.9).
5.14.3 Cry3Bb.11035
Changes were made in Cry3Bb to reflect the amino acid sequence in Cry3A at the end of lα3,4 and in the beginning of helix 4. These changes resulted in the designed protein, Cry3Bb.11035, that, unlike wild type Cry3Bb, forms spontaneous channels with large conductances. Cry3Bb.11035 is also approximately three times more active against SCRW larvae than WT Cry3Bb. Cry3Bb.11035 and its amino acid changes are listed in Table 10.
5.14.4 Cry3Bb.11032
Cry3Bb.11032 was altered at residue 165 in helix α4, changing an asparate to glycine, as found in Cry3A. Cry3Bb.11032 is three-fold more active than WT Cry3Bb. The channel activity of Cry3Bb.11032 is much like Cry3Bb except when the designed protein is artificially incorporated into the membrane. A 16-fold increase in the initial channel conductances is observed compared to WT Cry3Bb (see Section 5.12.2). This increase in initial conductance presumably is due to enhanced quaternary structure, stability or higher-order structure.
5.14.5 EG11224
In the WT Cry3Bb dimer structure, histidine, at position 231 in domain 1, makes hydrogen bond contacts with D288 (domain 1), Y230 (domain 1), and, through a network of water molecules, also makes contacts to D610 (domain 3), all of the opposite monomer. D610 and K235 (domain 1) also make contact. Replacing the histidine with an arginine, H231R, results, in one orientation, in the formation of a salt bridge to D610 of the neighboring monomer. In a second orientation, the contacts with D288 of the neighboring monomer, as appear in the WT structure, are retained. In either orientation, R231 does not hydrogen bond to Y230 of the opposite monomer but does make contact with K235 which retains is contacts to K610 (V. Cody, research communication). The shifting hydrogen bonds have changed the interactions between the different domains of the protein in the quaternary structure. Overall, fewer hydrogen bonds exist between domains 1 of the neighboring monomers and a much stronger bond has been formed between domains 1 and 3. Channel activity was found to be altered. Cry3Bb.11224 produces small, quickly gating channels like Cry3Bb. However, unlike WT Cry3Bb, Cry3Bb.11224 does not exhibit β-mercaptoethanol-dependent activation. Replacing H231 with arginine resulted in a designed Cry3Bb protein, Cry3Bb.11224, exhibiting a 5-fold increase in bioactivity.
5.14.6 Cry3Bb.11226
Cry3Bb.11226 is similar to Cry3Bb.11224, discussed in Section 4.8.5, in that the histidine at position 231 has been replaced. The amino acid change, H231T, results in the loss of β-mercaptoethanol dependent activation seen with WT Cry3Bb (see Section 5.12.1). The replacement of H231, a putative metal binding site, changes the interaction of regions in the quaternary structure resulting in a different type of channel activity. Cry3Bb.11226 is three-fold more active than WT Cry3Bb.
5.14.7 Cry3Bb.11221
Cry3Bb.11221 has been re-designed in the lα3,4 region of Cry3Bb. The channels formed by Cry3Bb.11221 are much more well resolved than the conductances formed by WT Cry3Bb (see Section 5.12.6). Cry3Bb.11221 exhibits a 6.4-fold increase in bioactivity over that of WT Cry3Bb. The amino acid changes found in Cry3Bb.11221 are listed in Table 2.
5.14.8 Cry3Bb.11242
The designed protein, Cry3Bb.11242, carrying the alteration R290V, forms small conductances immediately which grow rapidly and steadily to large conductances in about 3 min (see Section 5.12.7). This is contrast to WT Cry3Bb channels which take 30-45 min to appear and grow slowly over hours to large conductances. Cry3Bb.11242 also exhibits a 2.5-fold increase in bioactivity compared to WT Cry3Bb.
5.14.9 Cry3Bb.11230
Cry3Bb.11230, unlike WT Cry3Bb, forms well resolved channels with long open states. These channels reach a maximum conductance of 3000 pS but do not continue to grow with time. Cry3Bb.11230 has been re-designed in the lβ1,α8 region of Cry3Bb and exhibits almost a 5-fold increase in activity against SCRW larvae (Table 9) and a 5.4-fold increase against WCRW larvae (Table 10) compared to WT Cry3Bb. The amino acid changes found in Cry3Bb.11230 are listed in Table 2.
5.15 Example 15
Design Method 9: Design of Structural Residues
The specific three-dimensional structure of a protein is held in place by amino acids that may be buried or otherwise removed from the surface of the protein. These structural determinants can be identified by inspection of forces responsible for the surface structure positioning. The impact of these structural residues can then be enhanced to restrict molecular motion or diminished to enhance molecular flexibility.
5.15.1 Cry3Bb.11095
Loops β2,3, β6,7 and β10,11, located in domain 2 of Cry3Bb, have been identified as important for bioactivity. The three loops are surface-exposed and structurally close together. Amino acid Q348 in the WT structure, located in β-strand 2 just prior to lβ2,3, does not form any intramolecular contacts. However, replacing Q348 with arginine (Q348R) results in the formation of 2 new hydrogen-bonds between R348 and the backbone carbonyls of R487 and R488, both located in lβ10,11. The new hydrogen bonds may act to stabilize the structure formed by the three loops. Certainly, the structure around R348 is more tightly packed as determined by X-ray crystallography. The designed protein carrying this change, Cry3Bb.11095, is 4.6-fold more active than WT Cry3Bb.
5.16 Example 16
Design Method 10: Combinatorial Analysis and Mutagenesis
Individual sites in the engineered Cry3Bb molecule can be used together to create a Cry3Bb molecule with activity even greater than the activity of any one site. This method has not been precisely applied to any δ-endotoxin. It is also not obvious that improvements in two sites can be pulled together to improve the biological activity of the protein. In fact, data demonstrates that improvements to 2 sites, when pulled together into a single construct, do not necessarily further improve the biological activity of Cry3Bb. In some cases, the combination resulted in decreased protein stability and/or activity. Examples of proteins with site combinations that resulted in improved activity compared to WT Cry3Bb but decreased activity compared to 1 or more of the “parental” proteins are Cry3Bb.11235, 11046, 11057 and 11058. Cry3Bb.11082, which contains designed regions from 4 parental proteins, retains the level of activity from the most active parental strain (Cry3Bb.11230) but does not show an increase in activity. These proteins are listed in Table 7. The following are examples of instances where combined mutations have significantly improved biological activity.
5.16.1 Cry3Bb.11231
Designed protein Cry3Bb.11231 contains the alterations found in Cry3Bb.11224 (H231R) and Cry3Bb.11228 (changes in lβ1,α8). The combination of amino acid changes found in Cry3Bb.11231 results in an increase in bioactivity against SCRW larvae of approximately 8-fold over that of WT Cry3Bb (Table 2). This increase is greater than exhibited by either Cry3Bb.11224 (5.0×) or Cry3Bb.11228 (4.1×) alone. Cry3Bb.11231 was also exhibits an 12.9-fold increase in activity compared to WT Cry3Bb against WCRW larvae (Table 10).
5.16.2 Cry3Bb.11081
Designed Cry3Bb protein Cry3Bb.11081 was constructed by combining the changes found in Cry3Bb.1032 and Cry3Bb.11229 (with the exception of Y318C). Cry3Bb.11081 a 6.1-fold increase in activity over WT Cry3Bb; a greater increase in activity than either of the individual parental proteins, Cry3Bb.11032 (3.1-fold) and Cry3Bb.11229 (2.5-fold).
5.16.3 Cry3Bb.11083
Designed Cry3Bb protein Cry3Bb.11083 was constructed by combining the changes found in Cry3Bb.11036 and Cry3Bb.11095. Cry3Bb.11083 exhibits a 7.4-fold increase in activity against SCRW larvae compared to WT Cry3Bb; a greater increase than either Cry3Bb.11036 (4.3×) or Cry3Bb.11095 (4.6×). Cry3Bb.11083 also exhibits a 5.4-fold increase in activity against WCRW larvae compared to WT Cry3Bb (Table 10).
5.16.4 Cry3Bb.11084
Designed Cry3Bb protein Cry3Bb.11084 was constructed by combining the changes found in Cry3Bb.11032 and the S311L change found in Cry3Bb.11228. Cry3Bb.11084 exhibits a 7.2-fold increase in activity over that of WT Cry3Bb; a greater than either Cry3Bb.11032 (3.1×) or Cry3Bb.11228 (4.1×).
5.16.5 Cry3Bb.11098
Designed Cry3Bb protein Cry3Bb.11098 was constructed to contain the following amino acid changes: D165G, H231R, S311L, N313T, and E317K. The nucleic acid sequence is given in SEQ ID NO:107, and the encoded amino acid sequence is given in SEQ ID NO:108.
5.17 Example 17
Design Strategy 11: Alteration of Binding to Glycoproteins and to WCRW Brush Border Membranes
While the identity of receptor(s) for Cry3Bb is unknown, it is nonetheless important to increase the interaction of the toxin with its receptor. One way to improve the toxin-receptor interaction with knowing the identity of the receptor is to reduce or eliminate non-productive binding to other biomolecules. The inventors have observed that Cry3Bb binds non-specifically to bovine serum albumin (BSA) that has been glycosylated with a variety of sugar groups, but not to non-glycosylated BSA. Cry3A, which is not active on Diabrotica species, shows similar but even greater binding to glycosylated-BSA. Similarly, Cry3A shows greater binding to immobilized WCRW brush border membrane (BBM) than does WT Cry3Bb, suggesting that much of the observed binding is non-productive. It was reasoned that the non-specific binding to WCRW BBM occurs via glycosylated proteins, and that binding to both glycosylated-BSA and WCRW BBM is non-productive in reaction pathway to toxicity. Therefore reduction or elimination of that binding would lead to enhanced binding to the productive receptor and to enhanced toxicity. Potential binding sites for sugar groups were targeted for redesign to reduce the non-specific binding of Cry3Bb to glycoproteins and to immobilized WCRW BBM.
5.17.1 Cry3Bb.60
Cry3Bb-60, in which Cry3Bb has been cleaved at R159 in lα3,4, shows decreased binding to glycosylated-BSA and decreased binding to immobilized WCRW BBM. Cry3Bb-60 shows a 3.6-fold increase in bioactivity relative to WT Cry3Bb.
5.17.2 Alterations to lα3,4 (Cry3Bb.11221)
Cry3Bb.11221 has been redesigned in the lα3,4 region of domain 1, which is the region in which Cry3Bb is cleaved to produce Cry3Bb-60. Cry3Bb.11221 also shows decreased binding to both glycosylated-BSA and immobilized WCRW BBM, and exhibits a 6.4-fold increase in bioactivity over that of WT Cry3Bb. Together with data for Cry3Bb.60 (section 5.17.1) these data suggest that this loop region contributes substantially to non-productive binding of the toxin.
5.17.3 Alteration to 1β1,α8 (Cry3Bb.11228, 11230, 11237 and 11231)
The 1β,α8 region of Cry3Bb has been re-engineered to increase hydration (section 4.2.4) and enhance flexibility (section 4.4.3). Several proteins altered in this region, Cry3Bb.11228, 11230, and 11237 demonstrate substantially lower levels of binding both glycosylated-BSA and immobilized WCRW BBM, and also show between 4.1- and 4.5-fold increases in bioactivity relative to WT Cry3Bb.
5.17.4 Binding Activity
The tendencies of Cry3Bb and some of its derivatives to bind to glycosylated-BSA and to WCRW BBM were determined using a BIAcoreTM surface plasmon resonance biosensor. For glycosylated-BSA binding, the glycosylated protein was immobilized using standard NHS chemistry to a CM5 chip (BIAcore), and the solubilized toxin was injected over the glycosylated-BSA surface. To measure binding to WCRW BBM, brush border membrane vesicles (BBMV) purified from WCRW midguts (English et al., 1991) were immobilized on an HPA chip (BIAcore) then washed with either 10 mM KOH or with 40 mM β-octylglucoside. The solubilized toxin was then injected over the resulting hybrid bilayer surface to detect binding. Protein concentration were determined by Protein Dye Reagent assay (BioRad) or BCA Protein Assay (Pierce).
Other methods may also be used to determine the same binding information. These include, but are not limited to, ligand blot experiments using labeled toxin, labeled glycosylated protein, or anti-toxin antibodies, affinity chromatography, and in vitro binding of toxin to intact BBMV.
5.18 Example 18
Construction of plasmids with wt Cry3Bb Sequences
Standard recombinant DNA procedures were performed essentially as described by Sambrook et al., (1989).
5.18.1 pEG1701
pEG1701 (FIG. 11), contained in EG11204 and EG11037, was constructed by inserting the SphI-PstI fragment containing the cry3Bb gene and the cry1F terminator from pEG911 (Baum, 1994) into the SphI-PstI site of pEG854.9 (Baum et al., 1996), a high copy number B. thuringiensis-E. coli shuttle vector.
5.18.2 pEG1028
pEG1028 contains the HindIII fragment of cry3Bb from pEG1701 cloned into the multiple cloning site of pTZ18U at HindIII.
5.19 Example 19
Construction of Plasmids with Altered Cry3Bb Genes
Plasmid DNA from E. coli was prepared by the alkaline lysis method (Maniatis et al., 1982) or by commercial plasmid preparation kits (examples: PERFECTprepTM kit, 5 Prime-3 Prime, Inc., Boulder Colo.; QIAGEN plasmid prep kit, QIAGEN Inc.). B. thuringiensis plasmids were prepared from cultures grown in brain heart infusion plus 0.5% glycerol (BHIG) to mid logarithmic phase by the alkaline lysis method. When necessary for purification, DNA fragments were excised from an agarose gel following electrophoresis and recovered by glass milk using a Geneclean II® kit (BIO 101 Inc., La Jolla, Calif.). Alteration of the cry3Bb gene was accomplished using several techniques including site-directed mutagenesis, triplex PCRTM, quasi-random PCRTM mutagenesis, DNA shuffling and standard recombinant techniques. These techniques are described in Sections 6.1, 6.2, 6.3, 6.4 and 6.5, respectively. The DNA sequences of primers used are listed in Section 7.
5.20 Example 20
Site-Directed Mutagenesis
Site-directed mutagenesis was conducted by the protocols established by Kunkle (1985) and Kunkle et al. (1987) using the Muta-GeneTM M13 in vitro mutagenesis kit (BioRad, Richmond, Calif.). Combinations of alterations to cry3Bb were accomplished by using the Muta-GeneTM kit and multiple mutagenic oligonucleotide primers.
5.20.1 pEG1041
pEG1041, contained in EG11032, was constructed using the Muta-GeneTM kit, primer C, and single-stranded pEG1028 as the DNA template. The resulting altered cry3Bb DNA sequence was excised as a PflMI DNA fragment and used to replace the corresponding DNA fragment in pEG1701.
5.20.2 pEG1046
pEG1046, contained in EG11035, was constructed using the Muta-GeneTM kit, primer D, and single-stranded pEG1028 as the DNA template. The resulting altered cry3Bb DNA sequence was excised as a PflMI DNA fragment and used to replace the corresponding DNA fragment in pEG1701.
5.20.3 pEG1047
pEG1047, contained in EG11036, was constructed using the Muta-GeneTM kit, primer E, and single-stranded pEG1028 as the DNA template. The resulting altered cry3Bb DNA sequence was excised as a PflMI DNA fragment and used to replace the corresponding DNA fragment in pEG1701.
5.20.4 pEG1052
pEG1052, contained in EG11046, was constructed using the Muta-GeneTM kit, primers D and E, and single-stranded pEG1028 as the DNA template. The resulting altered cry3Bb DNA sequence was excised as a PflMI DNA fragment and used to replace the corresponding NA fragment in pEG1701.
5.20.5 pEG1054
pEG1054, contained in EG11048, was constructed using the Muta-GeneTM kit, primer F, and single-stranded pEG1028 as the DNA template. The resulting altered cry3Bb DNA sequence was excised as a PflMI DNA fragment and used to replace the corresponding DNA fragment in pEG1701.
5.20.6 pEG1057
pEG1057, contained in EG11051, was constructed using the Muta-GeneTM kit, primer G, and single-stranded pEG1028 as the DNA template. The resulting altered cry38b DNA sequence was excised as a PflMI DNA fragment and used to replace the corresponding DNA fragment in pEG1701.
5.21 Example 21
Triplex PCRTM
Triplex PCRTM is described by Michael (1994). This method makes use of a thermostable ligase to incorporate a phosphorylated mutagenic primer into an amplified DNA fragment during PCRTM. PCRTM was performed on a Perkin Elmer Cetus DNA Thermal Cycler (Perkin-Elmer, Norwalk, Conn.) using a AmpliTaqTM DNA polymerase kit (Perkin-Elmer) and SphI-linearized pEG1701 as the template DNA. PCRTM products were cleaned using commercial kits such as WizardTM PCRTM Preps (Promega, Madison, Wis.) and QIAquick PCRTM Purification kit (QIAGEN Inc., Chatsworth, Calif.).
5.21.1 pEG1708 and pEG1709
pEG1708 and pEG1709, contained in EG11222 and EG11223, respectively, were constructed by replacing the PflMI-PflMI fragment of cry3Bb in pEG1701 with PflMI-digested and gel purified PCRTM fragment altered at cry3Bb nucleotide positions 688-690, encoding amino acid Y230. Random mutations were introduced into the Y230 codon by triplex PCRTM. Mutagenic primer MVT095 was phosphorylated and used together with outside primer pair FW001 and FW006. Primer MVT095 also contains a silent mutation at position 687, changing T to C, which, upon incorporation, introduces an additional EcoRI site into pEG1701.
5.21.2 pEG1710, pEG1711 and pEG1712
Plasmids pEG1710, pEG1711 and pEG1712, contained in EG11224, EG11225 and EG11226, respectively, were created by replacing the PflMI-PflMI fragment of the cry3Bb gene in pEG1701 with PflMI-digested and gel purified PCRTM fragment altered at cry3Bb nucleotide positions 690-692, encoding H231. Random mutations were introduced into the H231 codon by triplex PCRTM. Mutagenic primer MVT097 was phosphorylated and used together with outside primer pair FW001 and FW006. Primer MVT097 also contains a T to C sequence change at position 687 which, upon incorporation, results in an additional EcoRI site by silent mutation.
5.21.3 pEG1713 and pEG1727
pEG1713 and pEG1727, contained in EG11227 and EG11242, respectively, were constructed by replacing the PflMI-PflMI fragment of the cry3Bb gene in pEG1701 with PflMI-digested and gel purified PCRTM fragment altered at cry3Bb nucleotide positions 868-870, encoding amino acid R290. Triplex PCRTM was used to introduce random changes into the R290 codon. The mutagenic primer, MVT091, was designed so that the nucleotide substitutions would result in approximately 36% of the sequences encoding amino acids D or E. MVT091 was phosphorylated and used together with outside primer pair FW001 and FW006.
5.22 Example 22
Quasi-Random PCRTM Mutagenesis
Quasi-random mutagenesis combines the mutagenic PCRTM techniques described by Vallette et al. (1989), Tomic et al. (1990) and LaBean and Kauffman (1993). Mutagenic primers, sometimes over 70 nucleotides in length, were designed to introduce changes over nucleotide positions encoding for an entire structural region, such as a loop. Degenerate codons typically consisted of a ratio of 82% WT nucleotide plus 6% each of the other 3 nucleotides per position to semi-randomly introduce changes over the target region (LaBean and Kauffman, 1993). When possible, natural restriction sites were utilized; class 2s enzymes were used when natural sites were not convenient (Stemmer and Morris, 1992, list additional restriction enzymes useful to this technique). PCRTM was performed on a Perkin Elmer Cetus DNA Thermal Cycler (Perkin-Elmer, Norwalk, Conn.) using a AmpliTaqTM DNA polymerase kit (Perkin-Elmer) and SphI-linearized pEG1701 as the template DNA. Quasi-random PCRTM amplification was performed using the following conditions: denaturation at 94° C. for 1.5 min.; annealing at 50° C. for 2 min. and extension at 72° C. for 3 min., for 30 cycles. The final 14 extension cycles were extended an additional 25 s per cycle. Primers concentration was 20 μM per reaction or 40 μM for long, mutagenic primers. PCRTM products were cleaned using commercial kits such as WizardTM PCRTM Preps (Promega, Madison, Wis.) and QIAquick PCRTM Purification kit (QIAGEN Inc., Chatsworth, Calif.). In some instances PCRTM products were treated with Klenow Fragment (Promega) following the manufacturer's instructions to fill in any single base overhangs prior to restriction digestion.
5.22.1 pEG1707
EG1707, contained in EG11221, was constructed by replacing the PflMI-PflMI fragment of the cry3Bb gene in pEG1701 with PflMI-digested and gel purified PCRTM fragment altered at cry3Bb nucleotide positions 460-480, encoding 1α3,4 amino acids 154-160. Primer MVT075, which includes a recognition site for the class 2s restriction enzyme BsaI, and primer FW006 were used to introduce changes into this region by quasi-random mutagenesis. Primers MVT076, also containing a BsaI site, and primer FW001 were used to PCRTM amplify a “linker” fragment. Following PCRTM amplification, both products were cleaned, end-filled, digested with BsaI and ligated to each other. Ligated fragment was gel purified and used as template for PCRTM amplification using primer pair FW001 and FW006. PCRTM product was cleaned, digested with PflMI, gel purified and ligated into PflMI-digested and purified pEG1701 vector DNA.
5.22.2 pEG1720 and pEG1726
pEG1720 and pEG1726, contained in EG11234 and EG11241, respectively, were constructed by replacing the PflMI-PflMI fragment of the cry3Bb gene in pEG1701 with PflMI-digested and gel purified PCRTM fragment altered at cry3Bb nucleotide positions 859-885, encoding 1α7,β1 amino acids 287-295. Quasi-random PCRTM mutagenesis was used to introduce changes into this region. Mutagenic primer MVT111, designed with a BsaI site, and primer FW006 were used to introduce the changes. Primer pair MVT094, also containing a BsaI site, and FW001 were used to amplify the linker fragment. The PCRTM products were digested with BsaI, gel purified then ligated to each other. Ligated product was PCRTM amplified using primer pair FW001 and FW006, digested with PflMI.
5.22.3 pEG1714, pEG1715, pEG1716, pEG1718, pEG1719, pEG1722, pEG1723, pEG1724 and pEG1725
pEG1714, pEG1715, pEG1716, pEG1718, pEG1719, pEG1722, pEG1723, pEG1724 and pEG1725, contained in EG11228, EG11229, EG11230, EG11232, EG11233, EG11236, EG11237, EG11238 and EG11239, respectively, were constructed by replacing the PflMI-PflMI fragment of the cry3Bb gene in pEG11701 with PflMI-digested and gel purified PCRTM fragment altered at cry3Bb nucleotide positions 931-954, encoding 1β1,α8 amino acids 311-318. Quasi-random PCRTM mutagenesis was used to introduce changes into this region using mutagenic primer MVT103 and primer FW006. Primers FW001 and FW006 were used to amplify a linker fragment. The PCRTM products were end-filled using Klenow and digested with BamHI. The larger fragment from the FW001-FW006 digest was gel purified then ligated to the digested MVT103-FW006 fragment. Ligated product was gel purified and amplified by PCRTM using primer pair FW001 and FW006. The amplified product was digested with PflMI and gel purified prior to ligation into PflMI-digested and purified pEG1701 vector DNA.
5.22.4 pEG1701.lβ2.3
Plasmids carrying alterations of cry3Bb WT sequence at nucleotides 1051-1065, encoding structural region lβ2,3 of Cry3Bb, were constructed by replacing the MluI-SpeI fragment of pEG1701 with isolated MluI- and SpeI-digested PCRTM product. The PCRTM product was generated by quasi-random PCRTM mutagenesis were mutagenic primer MVT081 was paired with FW0006. These plasmids as a group are designated pEG1701lβ2,3.
5.22.5 pEG1701.lβ6,7
Plasmids containing mutations of the cry3Bb WT sequence at nucleotides 1234-1248, encoding structural region lβ6,7 of Cry3Bb, were constructed by replacing the MluI-SpeI fragment of pEG1701 with isolated MluI- and SpeI-digested PCRTM product. The PCRTM product was generated by quasi-random PCRTM mutagenesis where mutagenic primer MVT085 was paired with primer WD115. Primer pair MVT089 and WD112 were used to amplify a linker fragment. Both PCRTM products were digested with TaqI and ligated to each other. The ligation product was gel purified and PCRTM amplified using primer pair MVT089 and FW006. The amplified product was digested with MluI and SpeI and ligated into MluI and SpeI digested and purified pEG1701 vector DNA. These plasmids as a group are designated pEG1701lβ6,7.
5.22.6 pEG1701lβ10,11
Plasmids containing mutated cry3Bb sequences at nucleotides 1450-1467, encoding structural region lβ0,11 of Cry3Bb, were constructed by replacing the SpeI-PstI fragment of pEG1701 with isolated SpeI- and PstI-digested PCRTM product. The PCRTM product was generated by quasi-random PCRTM mutagenesis where mutagenic primer MVT105 was paired with primer MVT070. Primer pair MVT092 and MVT083 were used to generate a linker fragment. (MVT083 is a mutagenic oligo designed for another region. The sequence changes introduced by MVT083 are removed following restriction digestion and do not impact the alteration of cry3Bb in the lβ10,11 region.) Both PCRTM products were digested with BsaI, ligated together, and the ligation product PCRTM amplified with primer pair MVT083 and MVT070. The resulting PCRTM product was digested with SpeI and PstI, and gel purified. These plasmids as a group are designated pEG1701.1β10,11.
5.23 Example 23
DNA Shuffling
DNA-shuffling, as described by Stemmer (1994), was used to combine individual alterations in the cry3Bb gene.
5.23.1 pEG1084, pEG1085, PEG 1086 and pEG1087
pEG1084, pEG1085, pEG1086, and pEG1087, contained in EG1081, EG11082, EG11083, and EG11084, respectively, were recovered from DNA-shuffling. Briefly, PflMI DNA fragments were generated using primer set A and B and each of the plasmids pEG1707, pEG1714, pEG1715, pEG1716, pEG1041, pEG1046, pEG1047, and pEG1054 as DNA templates. The resulting DNA fragments were pooled in equal-molar amounts and digested with DNaseI and 50-100 bp DNA fragments were recovered from an agarose gel by three successive freeze-thaw cycles: three min in a dry-ice ethanol bath followed by complete thawing at 50° C. The recovered DNA fragments were assembled by primerless-PCRTM and PCRTM-amplified using the primer set A and B as described by Stemmer (1994). The final PCRTM-amplified DNA fragments were cut with PflMI and used to replace the corresponding cry3Bb PflMI DNA fragment in pEG1701.
5.24 Example 24
Recombinant DNA Techniques
Standard recombinant DNA procedures were performed essentially as described by Sambrook et al. (1989).
5.24.1 pEG1717
pEG1717, contained in EG11231, was constructed by replacing the small BglII fragment of pEG1710 with the small BglII fragment from pEG1714.
5.24.2 pEG1721
pEG1721, contained in EG11235, was constructed by replacing the small BglII fragment from pEG1710 with the small BglII fragment from pEG1087.
5.24.3 pEG1063
pEG1062, contained in EG11057, was constructed by replacing the NcoI DNA fragment containing ori 43 from pEG1054 with the isolated NcoI DNA fragment containing ori 43 and the alterations in cry3Bb from pEG1046.
5.24.4 pEG1063
pEG1063, contained in EG11058, was constructed by replacing the NcoI DNA fragment containing ori 43 from pEG1054 with the isolated NcoI DNA fragment containing ori 43 and the alterations in cry3Bb from pEG1707.
5.24.5 pEG1095
pEG1095, contained in EG11095, was constructed by replacing the MluI-SpeI DNA fragment in pEG1701 with the corresponding MluI-SpeI DNA fragment from pEG1086.
5.25 Example 25
Primers Utilized in Constructing Cry3Bb* Variants
Shown below are the primers used for site-directed mutagenesis, triplex PCRTM and quasi-random PCRTM to prepare the cry3Bb* variants as described above. Primers were obtained from Ransom Hill Bioscience, Inc. (Ramona, Calif.) and Integrated DNA Technologies, Inc. (Coralville, Iowa). The specific composition of the primers containing particular degeneracies at one or more residues is given in Section 5.30, Example 30.
5.25.1 Primer FW001 (SEQ ID NO:71):









5′-AGACAACTCTACAGTAAAAGATG-3′






5.25.2 Primer FW006 (SEQ ID NO:72)










5′-GGTAATTGGTCAATAGAATC-3′






5.25.3 Primer MVT095 (SEQ ID NO:73):










5′-CAGAAGATGTTGCTGAATTCNNNCATAGACAATTAAAAC-3′






5.25.4 Primer MVT097 (SEQ ID NO:74):











5′-GATGTTGCTGAATTCTATNNNAGACAATTAAAAC-3′







5.25.5 Primer MVT091 (SEQ ID NO:75:











5′-CCCATTTTATGATATTBDNTTATACTCAAAAGG-3′







5.25.6 Primer MVT075 (SEQ ID NO:76):









5′-AGCTATGCTGGTCTCGGAAGAAAEFNFFNFJNJFJFJNFINJFJAAA



AGAAGCCAAGATCGAAT-3′






5.25.7 Primer MVT076 (SEQ ID NO:77):









5′-GGTCACCTAGGTCTCTCTTCCAGGAATTTAACGCATTAAC-3′







5.25.8 Primer MVT111 (SEQ ID NO:78):









5′-AGCTATGCTGGTCTCCCATTTJEHIEJEJJEIIKRRJEHEIJEENII



IGTTAAAACAGAACTAAC-3′






5.25.9 Primer MVT094 (SEQ ID NO:79):











5′-ATCCAGTGGGGTCTCAAATGGGAAAAGTACAATTAG-3′







5.25.10 Primer MVT103 (SEQ ID NO:80):









5′-CATTTTTACGGATCCAATTTTTJFFFJNEEJEFNFJNFEILEIJEOG



GACCAACTTTTTTGAG-3′






5.25.11 Primer MVT081 (SEQ ID NO:81):









5′-GAATTTCATACGCGTCTTCAACCTGGTJEHJJJIINMEEIEJTCTTT



CAATTATTGGTCTGG-3′






5.25.12 Primer MVT085 (SEQ ID NO:82):









5′-AAAAGTTTATCGAACTATAGCTAATACAGACGTAGCGGCTJQQFFNE



EJIIJEEIGTATATTTAGGTGTTACG-3′






5.25.13 Primer A (SEQ ID NO:83) 3b2 pflm1:











5′-GGAGTTCCATTTGCTGGGGC-3′







5.25.14 Primer B (SEQ ID NO:84) 3b2 pflm2:











5′-ATCTCCATAAAATGGGG-3′







5.25.15 Primer C (SEQ ID NO:85) 3b2165DG:











5′-GCGAAGTAAAAGAAGCCAAGGTCGAATAAGGG-3′







5.25.16 Primer D (SEQ ID NO:86) 3b2160SKRD:









5′-CCTTTAAGTTTGCGAAATCCACACAGCCAAGGTCGAATAAGGG-3′







5.25.17 Primer E (SEQ ID NO:87) 3b2290VP:











5′-CCCATTTTATGATGTTCGGTTATACCCAAAAGGGG-3′







5.25.18 Primer F (SEQ ID NO:88) 3b2EdA104:











5′-GGCCAAGTGAAGACCCATGGAAGGC-3′







5.25.19 Primer G (SEQ ID NO:89) 3b2KG189:










5′-GCAGTTTCCGGATTCGAAGTGC-3′






5.25.20 Primer WD112 (SEQ ID NO:90):










5′-CCGCTACGTCTGTATTA-3′






5.25.21 Primer WD115 (SEQ ID NO:91):










5′-ATAATGGAAGCACCTGA-3′






5.25.22 Primer MVT105 (SEQ ID NO:92):








5′-AGCTATGCTGGTCTCTTCTTAEJIFEIIEFFIJFIJIINACAATTCC


 


ATTTTTTACTTTGG-3′






5.25.23 Primer MVT092 (SEQ ID NO:93):








5′-ATCCAGTTGGGTCTCTAAGAAACAAACCGCGTAATTAAGC-3′






5.25.24 Primer MVT070 (SEQ ID NO:94):










5′-CCTCAAGGGTTATAACATCC-3′






5.25.25 Primer MVT083 (SEQ ID NO:95):








5′-GTACAAAAGCTAAGCTTTIEJIINPEEMEEIJNJESCGAACTATAGC


 


TAATACAG-3′






5.26 Example 26
Sequence Analysis of Altered cry3Bb Genes
E. coli DH5αTM (GIBCO BRL, Gaithersburg, Md.), JM110 and SureTM (Stratagene, La Jolla, Calif.) cells were sometimes used amplify plasmid DNA for sequencing. Plasmids were transformed into these cells using the manufacturers' procedures. DNA was sequenced using the Sequenase® 2.0 DNA sequencing kit purchased from U.S. Biochemical Corporation (Cleveland, Ohio). The plasmids described in Section 6, their respective divergence from WT cry3Bb sequence, the resulting amino acid changes and the protein structure site of the changes are listed in Table 11.







TABLE 11







DNA SEQUENCE CHANGES OF CRY3BB* GENES AND


RESULTING AMINO ACID SUBSTITUTIONS OF THE


CRY3BB* PROTEINS













Structural



cry3Bb* DNA
Cry3Bb* Amino
Site of


Plasmid
Sequence
Acid Sequence
Alteration





pEG1707
A460T, C461T,
T154F, P155H,
1α3, 4



A462T, C464A,
L156H, L158R




T465C, T466C,





T467A, A468T,





A469T, G470C,





T472C, T473G,





G474T, A477T,





A478T, G479C




 


pEG1708
T687C, T688C,
Y230L, H231S
α6



A689T, C691A,





A692G 




 


pEG1709
T667C, T687C,
S223P, Y230S
α6



T688A, A689G,





C691A, A692G




 


pEG1710
T687C, A692G
H231R
α6


 


pEG1711
T687C, C691A
H231N, T241S
α6


 


pEG1712
T687C, C691A,
H231T
α6



A692C, T693C




 


pEG1713
C868A, G869A,
R290N
1α7, β1



G870T




 


pEG1714
C932T, A938C,
S311L, N313T,
1β1, α8



T942G, G949A,
E317K




T954C




 


pEG1715
T931A, A933C,
S311T, E317K,
1β1, α8



T942A, T945A,
Y318C




G949A, A953G,





T954C




 


PEG1716
T931G, A933C,
S311A, L312V,
1β1, α8



C934G, T945G,
Q316W




C946T, A947G,





G951A, T954C




 


pEG1717
T687C, A692G,
H231R, S311L,
α6, 1β1,



C932T, A938C,
N313T, E317K
α8



T942G, G949A,





T954C




 


pEG1718
T931A, A933G,
S311T, L312P,
1β1, α8



T935C, T936A,
N313T, E317N




A938C, T939C,





T942C, T945A,





G951T, T954C




 


pEG1719
T931G, A933C,
S311A, Q316D
1β1, α8



T936G, T942C,





C943T, T945A,





C946G, G948C,





T954C




 


pEG1720
T861C, T866C,
I289T, L291R,
1α7, β1



C868A, T871C,
Y292F, S293R




T872G, A875T,





T877A, C878G,





A882G




 


pEG1721
T687C, A692G,
H231R, S311L
α6, 1β1,



C932T

α8


 


pEG1722
T931A, C932T,
S311I
1β1, α8



A933C, T936C,





T942G, T945A,





T954C




 


pEG1723
T931A, C932T,
S311I, N313H
1β1, α8



A933C, T936C,





A937G, A938T,





C941A, T942C,





T945A, C946A,





A947T, A950T,





T954C




 


pEG1724
A933C, T936C,
N313V, T314N,
1β1, α8



A937G, A938T,
Q316M, E317V




C941A, T942C,





T945A, C946A,





A947T, A950T,





T954C




 


pEG1725
A933T, A938G,
N313R, L315P,
1β1, α8



T939G, T942A,
Q316L, E317A




T944C, T945A,





A947T, G948T,





A950C, T954C




 


pEG1726
A860T, T861C,
Y287F, D288N,
1α7, β1



G862A, C868T,
R290L




G869T, T871C,





A873T, T877A,





C878G, A879T




 


pEG1727
C868G, G869T
R290V
1α7, β1


 


pEG1041
A494G
D165G
α4


 


pEG1046
G479A, A481C,
S160N, K161P,
α4



A482C, A484C,
R162H, D165G




G485A, A486C,





A494G




 


pEG1047
A865G, T877C
I289V, S293P
1α7, β1


 


pEG1052
G479A, A481C,
S160N, K161P,
α4, 1α7,



A482C, A484C,
R162H, D165G,
β1



G485A, A486C,
I289V, S293P




A494G, A865G,





T877C




 


pEG1054
T309A, Δ310,
D103E, ΔA104
1α2a, 2b



Δ311, Δ312




 


pEG1057
A565G, A566G
K189G
1α4, 5


 


pEG1062
T309A, Δ310,
D103E, ΔA104,
1α2a, 2b



Δ311, Δ312,
S160N, K161P,
α4



G479A, A481C,
R162H, D165G




A482C, A484C,





G485A, A486C,





A494G




 


pEG1063
T309A, Δ310,
D103E, ΔA104,
1α2a, 2b



Δ311, Δ312,
T154F, P155H,
1α3, 4



A460T, C461T,
L156H, L158R




A462T, C464A,





T465C, T466C,





T467A, A468T,





A469T, G470C,





T472C, T473G,





G474T, A477T,





A478T, G479C




 


pEG1084
A494G, T931A,
D165G, S311T,
α4, 1β1,



A933C, T942A,
E317K
α8



T945A, G949A,





T954C




 


pEG1085
A494G, A865G,
D165G, I289V,
α4, 1α7,



T877C, T914C,
S293P, F305S,
β1 βb,



T931G, A933C,
S311A, L312V,
1β1, α8



C934G, T945G,
Q316W, Q348R,




C946T, A947G,
V365A




G951A, T954C,





A1043G, T1094C




 


pEG1086
A865G, T877C,
I289V, S293P
1α7, β1,



A1043G
Q348R
β2


 


pEG1087
A494G, C932T
D165G, S311L
α4, 1β1,





α8


 


pEG1095
A1043G
Q348R
β2









5.27 Example 27
Expression of Cry3Bb* Proteins
5.27.1 Culture Conditions
LB agar was prepared using a standard formula (Maniatis et al., 1982). Starch agar was obtained from Difco Laboratories (Detroit, Mich.) and supplemented with an additional 5 g/l of agar. C2 liquid medium is described by Donovan et al. (1988). C2 medium was sometimes prepared without the phosphate buffer (C2-P). All cultures were incubated at 25° C. to 30° C.; liquid cultures were also shaken at 250 rpm, until sporulation and lysis had occurred.
5.27.2 Transformation Conditions
pEG1701 and derivatives thereof were introduced into acrystalliferious B. thuringiensis var. kurstaki EG7566 (Baum, 1994) or EG10368 (U.S. Pat. No. 5,322,687) by the electroporation method of Macaluso and Mettus (1991). In some cases, the method was modified as follows to maximize the number of transformants. The recipient B. thuringiensis strain was inoculated from overnight growth at 30° C. on LB agar into brain heart infusion plus 0.5% glycerol, grown to an optical density of approximately 0.5 at 600 nm, chilled on ice for 10 min, washed 2× with EB and resuspended in a 1/50 volume of EB. Transformed cells were selected on LB agar or starch agar plus 5 μg/ml chloramphenicol. Visual screening of colonies was used to identify transformants producing crystalline protein; those colonies were generally more opaque than colonies that did not produce crystalline protein.
5.27.3 Strain and Protein Designations
A transformant containing an altered cry3Bb* gene encoding an altered Cry3Bb* protein is designated by an “EG” number, e.g., EG11231. The altered Cry3Bb* protein is designated Cry3Bb followed by the strain number, e.g., Cry3Bb.11231. Collections of proteins with alterations at a structural site are designated Cry3Bb followed by the structural site, e.g., Cry3Bb.1β2,3. Table 12 lists the plasmids pertinent to this invention, the new B. thuringiensis strains containing the plasmids, the acrystalliferous B. thuringiensis recipient strain used, and the proteins produced by the new strains.
5.28 Example 28
Generation and Characterization of Cry3Bb-60
5.28.1 Generation of Cry3Bb-60
Cry3Bb-producing strain EG7231 (U.S. Pat. No. 5,187,091) was grown in C2 medium plus 3 mg/ml chloramphenicol. Following sporulation and lysis, the culture was washed with water and Cry3Bb protein purified by the NaBr solubilization and recrystallization method of Cody et al. (1992). Protein concentration was determined by BCA Protein Assay (Pierce, Rockford, Ill.). Recrystallized protein was solubilized in 10 ml of 50 mM KOH per 100 mg of Cry3Bb protein and buffered to pH 9.0 with 100 mM CAPS (3-[cyclohexylamino]-1-propanesulfonic acid), pH 9.0. The soluble toxin was treated with trypsin at a weight ratio of 50 mg toxin to 1 mg trypsin for 20 min to overnight at room temperature. Trypsin cleaves proteins on the carboxyl side of available arginine and lysine residues. For 8-dose bioassay, the solubilization conditions were altered slightly to increase the concentration of protein: 50 mM KOH was added dropwise to 2.7 ml of a 12.77 mg/ml suspension of purified Cry3Bb* until crystal solubilization occurred. The volume was then adjusted to 7 ml with 100 mM CAPS, pH 9.0.







TABLE 12







PLASMIDS CARRYING ALTERED CRY3BB* GENES


TRANSFORMED INTO B. THURINGIENSIS


FOR EXPRESSION OF ALTERED CRY3BB* PROTEINS









Plasmid Designation
New BT Strain
Expressed Protein





pEG1701
EG11204
WT Cry3Bb


pEG1701
EG11037
WT Cry3Bb


pEG1707
EG11221
Cry3Bb.11221


pEG1708
EG11222
Cry3Bb.11222


pEG1709
EG11223
Cry3Bb.11223


pEG1710
EG11224
Cry3Bb.11224


pEG1711
EG11225
Cry3Bb.11225


pEG1712
EG11226
Cry3Bb.11226


pEG1713
EG11227
Cry3Bb.11227


pEG1714
EG11228
Cry3Bb.11228


pEG1715
EG11229
Cry3Bb.11229


pEG1716
EG11230
Cry3Bb.11230


pEG1717
EG11231
Cry3Bb.11231


pEG1718
EG11232
Cry3Bb.11232


pEG1719
EG11233
Cry3Bb.11233


pEG1720
EG11234
Cry3Bb.11234


pEG1721
EG11235
Cry3Bb.11235


pEG1722
EG11236
Cry3Bb.11236


pEG1723
EG11237
Cry3Bb.11237


pEG1724
EG11238
Cry3Bb.11238


pEG1725
EG11239
Cry3Bb.11239


pEG1726
EG11241
Cry3Bb.11241


pEG1727
EG11242
Cry3Bb.11242


pEG1041
EG11032
Cry3Bb.11032


pEG1046
EG11035
Cry3Bb.11035


pEG1047
EG11036
Cry3Bb.11036


pEG1052
EG11046
Cry3Bb.11046


pEG1054
EG11048
Cry3Bb.11048


pEG1057
EG11051
Cry3Bb.11051


pEG1062
EG11057
Cry3Bb.11057


pEG1063
EG11058
Cry3Bb.11058


pEG1084
EG11081
Cry3Bb.11081


pEG1085
EG11082
Cry3Bb.11082


pEG1086
EG11083
Cry3Bb.11083


pEG1087
EG11084
Cry3Bb.11084


pEG1095
EG11095
Cry3Bb.11095


pEG1098
EG11098
Cry3Bb.11098


pEG1701.1β2,3
collection of unnamed strains
Cry3Bb.1β2,3


pEG1701.1β6,7
collection of unnamed strains
Cry3Bb.1β6,7


pEG1701.1β10,11
collection of unnamed strains
Cry3Bb.1β10,11









5.28.2 Determination of Molecular Weight of Cry3Bb-60

The molecular weight of the predominant trypsin digestion fragment of Cry3Bb was determined to be 60 kDa by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) analysis using commercial molecular weight markers. This digestion fragment is designated Cry3Bb-60. No further digestion of the 60 kDa cleavage product was observed.
5.28.3 Determination of NH2-Terminus of Cry3Bb-60
To determine the NH2-terminal sequence of Cry3Bb-60, the trypsin digest was fractionated by SDS-PAGE and transferred to ImmobilonTM-P membrane (Millipore Corporation, Bedford, Mass.) following standard western blotting procedures. After transfer, the membrane was rinsed twice with water then stained with 0.025% Coomassie Brilliant Blue R-250 plus 40% methanol for 5 min, destained with 50% methanol and rinsed in water. The Cry3Bb.60 band was excised with a razor blade. NH2-terminal sequencing was performed at the Tufts Medical School, Department of Physiology (Boston, Mass.) using standard automated Edman degradation procedures. The NH2-terminal amino acid sequence was determined to be SKRSQDR (SEQ ID NO:96), corresponding to amino acids 160-166 of Cry3Bb. Trypsin digestion occurred on the carboxyl side of amino acid R159 resulting in the removal of helices 1-3.
5.29 Example 29
Bioactivity of Cry3Bb* Proteins
5.29.1 Culture Conditions and Protein Concentration Determination
Cultures for 1-dose bioassays were grown in C2-P plus 5 μg/ml chloramphenicol (C2-P/cm5) then diluted with 3 volumes of 0.005% Triton X-100®. The protein concentrations of these cultures were not determined. Cultures for 8-dose bioassays were grown in C2/cm5, washed 1-2 times with 1-2 volumes of sterile water and resuspended in 1/10 volume of sterile 0.005% Triton X-100®. The toxin protein concentration of each concentrate was determined as described by Brussock and Currier (1990), omitting the treatment with 3 M HEPES. The protein concentration was adjusted to 3.2 mg/ml in 0.005% Triton X-100® for the top dose of the assay. Cry3Bb.60 was produced and quantified for 8-dose assay as described in Section 9.1.
5.29.2 Insect Bioassays
Diabrotica undecimpunctata howardi Barber (southern corn rootworm or SCRW) and Diabrotica virgifera virgifiera LeConte (western corn rootworm or WCRW) larvae were reared as described by Slaney et al. (1992). Eight-dose assays and probit analyses were performed as described by Slaney et al. (1992). Thirty-two larvae were tested per dose at 50 μl of sample per well of diet (surface area of 175 mm2). Positive controls were WT Cry3Bb-producing strains EG11037 or EG11204. All bioassays were performed using 128-well trays containing approximately 1 ml of diet per well with perforated mylar sheet covers (C-D International Inc., Pitman, N.J.). One-dose assays were performed essentially the same except only 1 dose was tested per strain. All assay were replicated at least twice.
5.29.3 Insect Bioassay Results: 1-Dose Assays Against SCRW
Results from 1-dose assays are expressed as the relative mortality (RM) of the experimental strain compared to WT (% mortality of experimental culture divided by % mortality of WT culture). Altered and improved Cry3Bb proteins derived from plasmids constructed using PCRTM methods introducing random or semi-random changes into the cry3Bb gene sequence were distinguished from other altered but not improved Cry3Bb proteins by replicated, 1-dose assay against SCRW larvae. Those proteins showing increased activity (defined as RM≧1.5) compared to WT Cry3Bb or, in the case of proteins with combinations of altered sites, compared to a “parental” altered Cry3Bb protein were further characterized by 8-dose assay. The overall RM “pattern” produced by 1-dose assay results from a collection of proteins carrying random or semi-random alterations within a single structural region, e.g., in 1β2,3, can be used to determine if that structural region is important for bioactivity.
Retention of WT levels of activity (RM≈1) indicate changes are tolerated in that region. Overall loss of activity (RM<1) distinguishes the region as important for bioactivity.
5.29.4 Cry3Bb.1β2,3: Results of 1-Dose Bioassays Against SCRW
Cry3Bb.1β2.3 protein are a collection of proteins altered in the 1β2,3 region of Cry3Bb (see Section 5.3.4). Typical results of 1-dose assays of these altered proteins are shown in FIG. 12. The RM values for Cry3Bb.1β2,3 proteins are less than 1, with a few exceptions of values close to 1, indicating that this region is important for toxicity.
5.29.5 Cry3Bb.l6,7: Results of 1-dose bioassays against SCRW
Cry3Bb.1β6,7 proteins are a collection of proteins altered in the 1β6,7 region of Cry3Bb (see Section 5.3.5). Typical results of 1-dose assays of these altered proteins are shown in FIG. 13. With a few exceptions of values close to 1, the RM values for Cry3Bb.1β6,7 proteins are less than 1, indicating that this region is important for toxicity.
5.29.6 Cry3Bb.1β10,11: Results of 1-Dose Bioassays Against SCRW
Cry3Bb.1β10,11 proteins are a collection of proteins altered in the 1β10,11 region of Cry3Bb (see Section 5.3.6). Typical results of 1-dose assays of these altered proteins are shown in FIG. 14. With a few exceptions of values close to 1, the RM values for Cry3Bb.1β10,11 proteins are less than 1, indicating that this region is important for bioactivity.
5.29.7 Insect Bioassay Results: Results of 8-Dose Assays Against SCRW
Results from 8-dose assays are expressed as an LC50 value (protein concentration giving 50% mortality) with 95% confidence intervals. The LC50 values with 95% confidence intervals of altered Cry3Bb proteins showing improved activities against SCRW larvae and LC50 values of the WT Cry3Bb control determined at the same time are listed in Table 13 along with the fold increase over WT activity for each improved protein.







TABLE 13







DESIGNED CRY3BB PROTEINS WERE TESTED AGAINST SCRW


LARVAE IN REPLICATED, 8-DOSE ASSAYS TO DETERMINE


THE LC50 VALUES










LC50 μg/well (95% C.I.)
Fold










Improved

WT Cry3Bb
Increase Over


Protein
Improved Protein
Control
WT Activity














Cry3Bb.60
6.7
(5.3-8.4)
24.1 (15-39)
3.6×


Cry3Bb.11221
3.2
(2.5-4)
  20.5 (14.5-29)
6.4×


Cry3Bb.11222
7.3
(6-9)
29.4 (23-37)
4.0×


Cry3Bb.11223
10.5
(9-12)
29.4 (23-37)
2.8×


Cry3Bb.11224
6.5
(5.1-8.2)
32.5 (25-43)
5.0×


Cry3Bb.11225
13.7
(11-16.8)
49.5 (39-65)
3.6×


Cry3Bb.11226
16.7
(10.6-24.2)
49.5 (39-65)
3.0×


Cry3Bb.11227
11.1
(9.1-13.5)
21.3 (16-28)
1.9×


Cry3Bb.11228
8.0
(6.6-9.8)
32.9 (25-45)
4.1×


Cry3Bb.11229
7.2
(5.8-8.8)
18.2 (15-22)
2.5×


Cry3Bb.11230
7.0
(5.8-8.6)
32.9 (25-45)
4.7×


Cry3Bb.11231
3.3
(3.0-3.7)
26.1 (22-31)
7.9×


Cry3Bb.11232
6.4
(5.4-7.7)
32.9 (25-45)
5.1×


Cry3Bb.11233
15.7
(12-20)
32.9 (25-45)
2.2×


Cry3Bb.11234
7
(6-9)
  29 (22-39)
4.1×


Cry3Bb.11235
4.2
(3.6-4.9)
13.3 (10-17)
3.2×


Cry3Bb.11236
11.6
(9-15)
36.4 (27-49)
3.1×


Cry3Bb.11237
6.8
(4-11)
36.4 (27-49)
5.4×


Cry3Bb.11238
13.9
(11-17)
36.4 (27-49)
2.6×


Cry3Bb.11239
13.0
(10-16)
36.4 (27-49)
2.8×


Cry3Bb.11241
11
(7-16)
  29 (22-39)
2.6×


Cry3Bb.11242
11.9
(9.2-16)
  30 (23-38)
2.5×


Cry3Bb.11032
4.2
(3.6-4.9)
13.3 (10-17)
3.1×


Cry3Bb.11035
10.3
(8-13)
27.9 (23-34)
2.7×


Cry3Bb.11036
6.5
(5.1-7.9)
27.9 (23-34)
4.3×


Cry3Bb.11046
12.1
(8-19)
31.2 (25-39)
2.6×


Cry3Bb.11048
8.3
(6-11)
35.4 (24-53)
4.3×


Cry3Bb.11051
11.8
(8-16)
35.4 (24-53)
3.0×


Cry3Bb.11057
8.8
(7-11)
29.5 (24-36)
3.4×


Cry3Bb.11058
9.6
(6-14)
33.4 (27-43)
3.5×


Cry3Bb.11081
8.5
(7-11)
51.5 (37-79)
6.1×


Cry3Bb.11082
10.6
(8-13)
51.5 (37-79)
4.9×


Cry3Bb.11083
7.0
(5-10)
51.5 (37-79)
7.4×


Cry3Bb.11084
7.2
(4-12)
51.5 (37-79)
7.2×


Cry3Bb.11095
11.1
(9-14)
51.5 (37-79)
4.6×


Cry3Bb.11098









5.29.8 Insect Bioassay Results: 8-Dose Assays Against WCRW

WCRW larvae are delicate and difficult to work with. Therefore, only some of the designed Cry3Bb showing improved activity against SCRW larvae were also tested against WCRW larvae in 8-dose assays. The LC50 determinations for the designed Cry3Bb proteins are shown in Table 14 along with the LC50 values of the WT Cry3Bb control determined at the same time.







TABLE 14







CRY3BB* PROTEINS SHOWING IMPROVED ACTIVITY


AGAINST SCRW LARVAE ALSO SHOW IMPROVED


ACTIVITY AGAINST WCRW LARVAE










LC50 μg/well (95% C.I.)











Improved

WT Cry3Bb
Fold Increase Over


Protein
Improved Protein
Control
WT Activity













EG11083
  6.3 (4.7-8.2)
63.5 (46-91) 
10.1×


EG11230
24.2 (13-40)
4.5 (2.1-7.4)
5.4×


EG11231
32.2 (14-67)
2.5 (1.7-3.6)
12.9×









5.30 Example 30
Channel Activity
Ion channels produced by Cry3Bb and some of its derivatives were measured by the methods described by Slatin et al. (1990). In some instances, lipid bilayers were prepared from a mixture of 4:1 phophatidylethanolamine (PE):phosphatidylcholine (PC). Toxin protein was solubilized from washed, C2 medium, B. thuringiensis cultures with 12 mM KOH. Following centrifugation to remove spores and other debris, 10 μg of soluble toxin protein was added to the cis compartment (4.5 ml volume) of the membrane chamber. Protein concentration was determined using the BCA Protein Assay (Pierce).
5.30.1 Channel activity of wt Cry3Bb.
Upon exposure to black lipid membranes, Cry3Bb forms ion channels with various conductance states. The channels formed by Cry3Bb are rarely discrete channels with well resolved open and closed states and usually require incubation of the toxin with the membrane for 30-45 min before any channel-like events are observed. After formation of the initial conductances, the size increases from approximately 200 pS to over 10,000 pS over 2-3 h. Only the small conductances (≦200 pS) are voltage dependent. Over 200 pS, the conductances are completely symmetric. Cry3Bb channels also exhibit β-mercaptoethanol-dependent activation, growing from small channel conductances of  ̃200 pS to several thousand pS within 2 min of the addition of β-mercaptoethanol to the cis compartment of the membrane chamber.
5.30.2 Cry3Bb.11032
The channel activity of Cry3Bb.11032 is much like WT Cry3Bb when the solubilized toxin protein is added to the cis compartment of the membrane chamber. However, when this protein is artificially incorporated into the membrane by forming or “painting” the membrane in the presence of the Cry3Bb.11032 protein, a 16-fold increase in the initial channel conductances is observed ( ̃4000 pS). This phenomenon is not observed with WT Cry3Bb.
5.30.3 Cry3Bb.11035
Upon exposure to artificial membranes, the Cry3Bb.11035 protein spontaneously forms channels that grow to large conductances within a relatively short time span ( ̃5 min).
Conductance values ranges from 3000-6000 pS and, like WT Cry3Bb, are voltage dependent at low conductance values.
5.30.4 Cry3Bb.11048
The Cry3Bb.11048 protein is quite different than WT Cry3Bb in that it appears not to form channels at all, but, rather, forms symmetrical pores with respect to voltage. Once the pore is formed, it remains open and allows a steady conductance ranging from 25 to 130 pS.
5.30.5 Cry3Bb.11224 and Cry3Bb.11226
The metal binding site of WT Cry3Bb formed by H231 in the dimer structure was removed in proteins Cry3Bb.11224 and Cry3Bb.11226. The conductances formed by both designed proteins are identical to that of WT Cry3Bb with the exception that neither of the designed proteins exhibits β-mercaptoethanol-dependent activation.
5.30.6 Cry3Bb.11221
Cry3Bb.11221 protein has been observed to immediately form small channels of 100-200 pS with limited voltage dependence. Some higher conductances were observed at the negative potential. In other studies, the onset of activity was delayed by 27 min, which is more typical for WT Cry3Bb. Unlike WT Cry3Bb, however, Cry3Bb.11221 forms well resolved, 600 pS channels with long open states. The protein eventually reaches conductances of 7000 pS.
5.30.7 Cry3Bb.11242
Cry3Bb.11242 protein forms small conductances immediately upon exposure to an artificial membrane. The conductances grow steadily and rapidly to 6000 pS in approximately 3 min. Some voltage dependence was noted with a preference for a negative imposed voltage.
5.30.8 Cry3Bb.11230
Unlike WT Cry3Bb, Cry3Bb.11230 forms well resolved channels with long open states that do not continue to grow in conductance with time. The maximum observed channel conductances reached 3000 pS. FIG. 15 illustrates the difference between the channels formed by Cry3Bb and Cry3Bb.11230.
5.30.9 Cry3Bb.60
Cry3Bb.60 forms well resolved ion channels within 20 min of exposure to an artificial membrane. These channels grow in conductance and frequency with time. The behavior of Cry3Bb.60 in a planar lipid bilayer differs from Cry3Bb in two significant ways. The conductances created by Cry3Bb.60 form more quickly than Cry3Bb and, unlike Cry3Bb, the conductances are stable, having well resolved open and closed states definitive of stable ion channels (FIG. 16).
5.31 Example 31
Primer Compositions









TABLE 15







SEQ ID NO: 83
% of Nucleotide in mixture












Code
A
T
G
C





N
25
25
25
25


















TABLE 16







SEQ ID NO: 84
% of Nucleotide in mixture












Code
A
T
G
C





N
25
25
25
25


















TABLE 17







SEQ ID NO: 85
% of Nucleotide in mixture












Code
A
T
G
C





B
16
16
52
16


 


D
70
10
10
10


 


N
25
25
25
25


















TABLE 18







SEQ ID NO: 86
% of Nucleotide in mixture












Code
A
T
G
C














E
82
6
6
6


 


F
6
6
6
82 


 


J
6
82 
6
6


 


I
6
6
82 
6


 


N
25 
25 
25 
25 


















TABLE 19







SEQ ID NO: 88
% of Nucleotide in mixture












Code
A
T
G
C














J
 6
82
 6
 6


 


E
82
 6
 6
 6


 


H
 1
 1
 1
97


 


I
 6
 6
82
 6


 


K
15
15
15
55


 


R
15
55
15
15


















TABLE 20







SEQ ID NO: 90
% of Nucleotide in mixture












Code
A
T
G
C














J
6
82 
6
6


 


F
6
6
6
82 


 


N
25 
25 
25 
25 


 


E
82 
6
6
6


 


I
6
6
82 
6


 


L
8
1
83 
8


 


O
1
1
1
97 


















TABLE 21







SEQ ID NO: 91
% of Nucleotide in mixture












Code
A
T
G
C














J
 6
82 
6
6


 


E
82
6
6
6


 


H
 1
1
1
97 


 


I
 6
6
82 
6


 


N
25
25 
25 
25 


 


M
82
2
8
8
















TABLE 22







SEQ ID NO: 92










% of Nucleotide in mixture












Code
A
T
G
C














J
6
82 
 6
6


 


Q
0
9
82
9


 


F
6
6
 6
82 


 


N
25 
25 
25
25 


 


E
82 
6
 6
6


 


I
6
6
82
6
















TABLE 23







SEQ ID NO: 92










% of Nucleotide in mixture












Code
A
T
G
C














J
6
82
6
6


 


F
6
6
6
82


 


N
25
25
25
25


 


E
82
6
6
6


 


I
6
6
82
6
















TABLE 24







SEQ ID NO: 95










% of Nucleotide in mixture












Code
A
T
G
C














J
6
82
6
6


 


N
25
25
25
25


 


E
82
6
6
6


 


I
6
6
82
6


 


M
82
2
8
8


 


P
8
2
8
82


 


S
1
97
1
1









5.32 Example 32
Atomic Coordinates for Cry3Bb
The atomic coordinates of the Cry3Bb protein are given in the Appendix included in Section 9.1
5.33 Example 33
Atomic coordinates for cry3A
The atomic coordinates of the Cry3A protein are given in the Appendix included in Section 9.2
5.34 Example-34
Modification of Cry Genes for Expression in Plants
Wild-type cry genes are known to be expressed poorly in plants as a full length gene or as a truncated gene. Typically, the G+C content of a cry gene is low (37%) and often contains many A+T rich regions, potential polyadenylation sites and numerous ATTTA sequences. Table 25 shows a list of potential polyadenylation sequences which should be avoided when preparing the “plantized” gene construct.







TABLE 25





LIST OF SEQUENCES OF THE POTENTIAL POLYADENY-


LATION SIGNALS


















AATAAA*
AAGCAT


 



AATAAT*
ATTAAT


 



AACCAA
ATACAT


 



ATATAA
AAAATA


 



AATCAA
ATTAAA**


 



ATACTA
AATTAA**


 



ATAAAA
AATACA**


 



ATGAAA
CATAAA**





*indicates a potential major plant polyadenylation site.


**indicates a potential minor animal polyadenylation site.


All others are potential minor plant polyadenylation sites.






The regions for mutagenesis may be selected in the following manner. All regions of the DNA sequence of the cry gene are identified which contained five or more consecutive base pairs which were A or T. These were ranked in terms of length and highest percentage of A+T in the surrounding sequence over a 20-30 base pair region. The DNA is analysed for regions which might contain polyadenylation sites or ATTTA sequences. Oligonucleotides are then designed which maximize the elimination of A+T consecutive regions which contained one or more polyadenylation sites or ATTTA sequences. Two potential plant polyadenylation sites have been shown to be more critical based on published reports. Codons are selected which increase G+C content, but do not generate restriction sites for enzymes useful for cloning and assembly of the modified gene (e.g., BamHI, BglII, SacI, NcoI, EcoRV, etc.). Likewise condons are avoided which contain the doublets TA or GC which have been reported to be infrequently-found codons in plants.
Although the CaMV35S promoter is generally a high level constitutive promoter in most plant tissues, the expression level of genes driven the CaMV35S promoter is low in floral tissue relative to the levels seen in leaf tissue. Because the economically important targets damaged by some insects are the floral parts or derived from floral parts (e.g., cotton squares and bolls, tobacco buds, tomato buds and fruit), it is often advantageous to increase the expression of crystal proteins in these tissues over that obtained with the CaMV35S promoter.
The 35S promoter of Figwort Mosaic Virus (FMV) is analogous to the CaMV35S promoter. This promoter has been isolated and engineered into a plant transformation vector. Relative to the CaMV promoter, the FMV 35S promoter is highly expressed in the floral tissue, while still providing similar high levels of gene expression in other tissues such as leaf. A plant transformation vector, may be constructed in which the full length synthetic cry gene is driven by the FMV 35S promoter. Tobacco plants may be transformed with the vector and compared for expression of the crystal protein by Western blot or ELISA immunoassay in leaf and floral tissue. The FMV promoter has been used to produce relatively high levels of crystal protein in floral tissue compared to the CaMV promoter.
5.35 Example 35
Expression of Synthetic Cry Genes with ssRUBISCO Promoters and Chloroplast Transit Peptides
The genes in plants encoding the small subunit of RUBISCO(SSU) are often highly expressed, light regulated and sometimes show tissue specificity. These expression properties are largely due to the promoter sequences of these genes. It has been possible to use SSU promoters to express heterologous genes in transformed plants. Typically a plant will contain multiple SSU genes, and the expression levels and tissue specificity of different SSU genes will be different. The SSU proteins are encoded in the nucleus and synthesized in the cytoplasm as precursors that contain an N-terminal extension known as the chloroplast transit peptide (CTP). The CTP directs the precursor to the chloroplast and promotes the uptake of the SSU protein into the chloroplast. In this process, the CTP is cleaved from the SSU protein. These CTP sequences have been used to direct heterologous proteins into chloroplasts of transformed plants.
The SSU promoters might have several advantages for expression of heterologous genes in plants. Some SSU promoters are very highly expressed and could give rise to expression levels as high or higher than those observed with the CaMV35S promoter. The tissue distribution of expression from SSU promoters is different from that of the CaMV35S promoter, so for control of some insect pests, it may be advantageous to direct the expression of crystal proteins to those cells in which SSU is most highly expressed. For example, although relatively constitutive, in the leaf the CaMV35S promoter is more highly expressed in vascular tissue than in some other parts of the leaf, while most SSU promoters are most highly expressed in the mesophyll cells of the leaf. Some SSU promoters also are more highly tissue specific, so it could be possible to utilize a specific SSU promoter to express the protein of the present invention in only a subset of plant tissues, if for example expression of such a protein in certain cells was found to be deleterious to those cells. For example, for control of Colorado potato beetle in potato, it may be advantageous to use SSU promoters to direct crystal protein expression to the leaves but not to the edible tubers.
Utilizing SSU CTP sequences to localize crystal proteins to the chloroplast might also be advantageous. Localization of the B. thuringiensis crystal proteins to the chloroplast could protect these from proteases found in the cytoplasm. This could stabilize the proteins and lead to higher levels of accumulation of active toxin. cry genes containing the CTP could be used in combination with the SSU promoter or with other promoters such as CaMV35S.
5.36 Example 36
Targeting of Cry* Proteins to the Extracellular Space or Vacuole Through the Use of Signal Peptides
The B. thuringiensis proteins produced from the synthetic genes described here are localized to the cytoplasm of the plant cell, and this cytoplasmic localization results in plants that are insecticidally effective. It may be advantageous for some purposes to direct the B. thuringiensis proteins to other compartments of the plant cell. Localizing B. thuringiensis proteins in compartments other than the cytoplasm may result in less exposure of the B. thuringiensis proteins to cytoplasmic proteases leading to greater accumulation of the protein yielding enhanced insecticidal activity. Extracellular localization could lead to more efficient exposure of certain insects to the B. thuringiensis proteins leading to greater efficacy. If a B. thuringiensis protein were found to be deleterious to plant cell function, then localization to a noncytoplasmic compartment could protect these cells from the protein.
In plants as well as other eukaryotes, proteins that are destined to be localized either extracellularly or in several specific compartments are typically synthesized with an N-terminal amino acid extension known as the signal peptide. This signal peptide directs the protein to enter the compartmentalization pathway, and it is typically cleaved from the mature protein as an early step in compartmentalization. For an extracellular protein, the secretory pathway typically involves cotranslational insertion into the endoplasmic reticulum with cleavage of the signal peptide occurring at this stage. The mature protein then passes through the Golgi body into vesicles that fuse with the plasma membrane thus releasing the protein into the extracellular space. Proteins destined for other compartments follow a similar pathway. For example, proteins that are destined for the endoplasmic reticulum or the Golgi body follow this scheme, but they are specifically retained in the appropriate compartment. In plants, some proteins are also targeted to the vacuole, another membrane bound compartment in the cytoplasm of many plant cells. Vacuole targeted proteins diverge from the above pathway at the Golgi body where they enter vesicles that fuse with the vacuole.
A common feature of this protein targeting is the signal peptide that initiates the compartmentalization process. Fusing a signal peptide to a protein will in many cases lead to the targeting of that protein to the endoplasmic reticulum. The efficiency of this step may depend on the sequence of the mature protein itself as well. The signals that direct a protein to a specific compartment rather than to the extracellular space are not as clearly defined. It appears that many of the signals that direct the protein to specific compartments are contained within the amino acid sequence of the mature protein. This has been shown for some vacuole targeted proteins, but it is not yet possible to define these sequences precisely. It appears that secretion into the extracellular space is the “default” pathway for a protein that contains a signal sequence but no other compartmentalization signals. Thus, a strategy to direct B. thuringiensis proteins out of the cytoplasm is to fuse the genes for synthetic B. thuringiensis genes to DNA sequences encoding known plant signal peptides. These fusion genes will give rise to B. thuringiensis proteins that enter the secretory pathway, and lead to extracellular secretion or targeting to the vacuole or other compartments. Signal sequences for several plant genes have been described. One such sequence is for the tobacco pathogenesis related protein PR1b has been previously described (Cornelissen et al., 1986). The PR1b protein is normally localized to the extracellular space. Another type of signal peptide is contained on seed storage proteins of legumes. These proteins are localized to the protein body of seeds, which is a vacuole like compartment found in seeds. A signal peptide DNA sequence for the β-subunit of the 7S storage protein of common bean (Phaseolus vulgaris), PvuB has been described (Doyle et al., 1986). Based on the published these published sequences, genes may be synthesized chemically using oligonucleotides that encode the signal peptides for PR1b and PvuB. In some cases to achieve secretion or compartmentalization of heterologous proteins, it may be necessary to include some amino acid sequence beyond the normal cleavage site of the signal peptide. This may be necessary to insure proper cleavage of the signal peptide.
5.37 Example 37
Isolation of Transgenic Maize Resistant to Diabrotica spp. Using Cry3Bb Variants
5.37.1 Plant Gene Construction
The expression of a plant gene which exists in double-stranded DNA form involves transcription of messenger RNA (mRNA) from one strand of the DNA by RNA polymerase enzyme, and the subsequent processing of the mRNA primary transcript inside the nucleus. This processing involves a 3′ non-translated region which adds polyadenylate nucleotides to the 3′ end of the RNA. Transcription of DNA into mRNA is regulated by a region of DNA usually referred to as the “promoter”. The promoter region contains a sequence of bases that signals RNA polymerase to associate with the DNA and to initiate the transcription of mRNA using one of the DNA strands as a template to make a corresponding strand of RNA.
A number of promoters which are active in plant cells have been described in the literature. Such promoters may be obtained from plants or plant viruses and include, but are not limited to, the nopaline synthase (NOS) and octopine synthase (OCS) promoters (which are carried on tumor-inducing plasmids of Agrobacterium tumefaciens), the cauliflower mosaic virus (CaMV) 19S and 35S promoters, the light-inducible promoter from the small subunit of ribulose 1,5-bisphosphate carboxylase (ssRUBISCO, a very abundant plant polypeptide), and the Figwort Mosaic Virus (FMV) 35S promoter. All of these promoters have been used to create various types of DNA constructs which have been expressed in plants (see e.g., U.S. Pat. No. 5,463,175, specifically incorporated herein by reference).
The particular promoter selected should be capable of causing sufficient expression of the enzyme coding sequence to result in the production of an effective amount of protein. One set of preferred promoters are constitutive promoters such as the CaMV35S or FMV35S promoters that yield high levels of expression in most plant organs (U.S. Pat. No. 5,378,619, specifically incorporated herein by reference). Another set of preferred promoters are root enhanced or specific promoters such as the CaMV derived 4 as-1 promoter or the wheat POX1 promoter (U.S. Pat. No. 5,023,179, specifically incorporated herein by reference; Hertig et al., 1991). The root enhanced or specific promoters would be particularly preferred for the control of corn rootworm (Diabroticus spp.) in transgenic corn plants.
The promoters used in the DNA constructs (i.e. chimeric plant genes) of the present invention may be modified, if desired, to affect their control characteristics. For example, the CaMV35S promoter may be ligated to the portion of the ssRUBISCO gene that represses the expression of ssRUBISCO in the absence of light, to create a promoter which is active in leaves but not in roots. The resulting chimeric promoter may be used as described herein. For purposes of this description, the phrase “CaMV35S” promoter thus includes variations of CaMV35S promoter, e.g., promoters derived by means of ligation with operator regions, random or controlled mutagenesis, etc. Furthermore, the promoters may be altered to contain multiple “enhancer sequences” to assist in elevating gene expression.
The RNA produced by a DNA construct of the present invention also contains a 5′ non-translated leader sequence. This sequence can be derived from the promoter selected to express the gene, and can be specifically modified so as to increase translation of the mRNA. The 5′ non-translated regions can also be obtained from viral RNA's, from suitable eucaryotic genes, or from a synthetic gene sequence. The present invention is not limited to constructs wherein the non-translated region is derived from the 5′ non-translated sequence that accompanies the promoter sequence.
For optimized expression in monocotyledenous plants such as maize, an intron should also be included in the DNA expression construct. This intron would typically be placed near the 5′ end of the mRNA in untranslated sequence. This intron could be obtained from, but not limited to, a set of introns consisting of the maize hsp70 intron (U.S. Pat. No. 5,424,412; specifically incorporated herein by reference) or the rice Act1 intron (McElroy et al., 1990). As shown below, the maize hsp70 intron is useful in the present invention.
As noted above, the 3′ non-translated region of the chimeric plant genes of the present invention contains a polyadenylation signal which functions in plants to cause the addition of adenylate nucleotides to the 3′ end of the RNA. Examples of preferred 3′ regions are (1) the 3′ transcribed, non-translated regions containing the polyadenylate signal of Agrobacterium tumor-inducing (Ti) plasmid genes, such as the nopaline synthase (NOS) gene and (2) plant genes such as the pea ssRUBISCO E9 gene (Fischhoff et al., 1987).
5.37.2 Plant Transformation and Expression
A chimeric plant gene containing a structural coding sequence of the present invention can be inserted into the genome of a plant by any suitable method. Suitable plant transformation vectors include those derived from a Ti plasmid of Agrobacterium tumefaciens, as well as those disclosed, e.g., by Herrera-Estrella (1983), Bevan (1983), Klee (1985) and Eur. Pat. Appl. Publ. No. EP0120516. In addition to plant transformation vectors derived from the Ti or root-inducing (R1) plasmids of Agrobacterium, alternative methods can be used to insert the DNA constructs of this invention into plant cells. Such methods may involve, for example, the use of liposomes, electroporation, chemicals that increase free DNA uptake, free DNA delivery via microprojectile bombardment, and transformation using viruses or pollen (Fromm et al., 1986; Armstrong et al., 1990; Fromm et al., 1990).
5.37.3 Construction of Monocot Plant Expression Vectors for Cry3Bb Variants
5.37.3.1 Design of Cry3Bb Variant Genes for Plant Expression
For efficient expression of the cry3Bb variants in transgenic plants, the gene encoding the variants must have a suitable sequence composition (Diehn et al., 1996). One example of such a sequence is shown for the v11231 gene (SEQ ID NO:99) which encodes the Cry3Bb11231 variant protein (SEQ ID NO:100) with Diabrotica activity. This gene was derived via mutagenesis (Kunkel, 1985) of a cry3Bb synthetic gene (SEQ ID NO:1101) encoding a protein essentially homologous to the protein encoded by the native cry3Bb gene (Gen Bank Accession Number m89794, SEQ ID NO:102). The following oligonucleotides were used in the mutagenesis of the original cry3Bb synthetic gene (SEQ ID NO:101) to create the v11231 gene (SEQ ID NO:99):







Oligo #1:


(SEQ ID NO: 103)


5′-TAGGCCTCCATCCATGGCAAACCCTAACAATC-3′


 


Oligo #2:


(SEQ ID NO: 104)


5′-TCCCATCTTCCTACTTACGACCCTGCAGAAATACGGTCCAAC-3′


 


Oligo #3:


(SEQ ID NO:105)


5-GACCTCACCTACCAAACATTCGATCTTG-3′


 


Oligo #4:


(SEQ ID NO:106)


5′-CGAGTTCTACCGTAGGCAGCTCAAG-3′






5.37.3.2 Construction of Cry3Bb Monocot Plant Expression Vector

To place the cry3Bb variant gene v11231 in a vector suitable for expression in monocotyledonous plants (i.e. under control of the enhanced Cauliflower Mosaic Virus 35S promoter and link to the hsp70 intron followed by a nopaline synthase polyadenylation site as in U.S. Pat. No. 5,424,412, specifically incorporated herein by reference), the vector pMON19469 was digested with NcoI and EcoRI. The larger vector band of approximately 4.6 kb was electrophoresed, purified, and ligated with T4 DNA ligase to the NcoI-EcoRI fragment of approximately 2 kb containing the v11231 gene (SEQ ID NO:99). The ligation mix was transformed into E. coli, carbenicillin resistant colonies recovered and plasmid DNA recovered by DNA miniprep procedures. This DNA was subjected to restriction endonuclease analysis with enzymes such as NcoI and EcoRI (together). NotI, and PstI to identify clones containing pMON33708 (the v1231 coding sequence fused to the hsp70 intron under control of the enhanced CaMV35S promoter).
To place the v11231 gene in a vector suitable for recovery of stably transformed and insect resistant plants, the 3.75-kb NotI restriction fragment from pMON33708 containing the lysine oxidase coding sequence fused to the hsp70 intron under control of the enhanced CaMV35S promoter was isolated by gel electrophoresis and purification. This fragment was ligated with pMON30460 treated with NotI and calf intestinal alkaline phosphatase (pMON30460 contains the neomycin phosphotransferase coding sequence under control of the CaMV35S promoter). Kanamycin resistant colonies were obtained by transformation of this ligation mix into E. coli and colonies containing pMON33710 identified by restriction endonuclease digestion of plasmid miniprep DNAs. Restriction enzymes such as NotI, EcoRV, HindIII, NcoI, EcoRI, and BglII can be used to identify the appropriate clones containing the NotI fragment of pMON33708 in the NotI site of pMON30460 (i.e. pMON33710) in the orientation such that both genes are in tandem (i.e. the 3′ end of the v11231 expression cassette is linked to the 5′ end of the nptII expression cassette). Expression of the v11231 protein by pMON33710 in corn protoplasts was confirmed by electroporation of pMON33710 DNA into protoplasts followed by protein blot and ELISA analysis. This vector can be introduced into the genomic DNA of corn embryos by particle gun bombardment followed by paromomycin selection to obtain corn plants expressing the v11231 gene essentially as described in U.S. Pat. No. 5,424,412, specifically incorporated herein by reference.
In this example, the vector was introduced via cobombardment with a hygromycin resistance conferring plasmid into immature embryo scutella (IES) of maize, followed by hygromycin selection, and regeneration. Transgenic corn lines expressing the v11231 protein were identified by ELISA analysis. Progeny seed from these events were subsequently tested for protection from Diabrotica feeding.
5.37.3.3 In Planta Performance of Cry3Bb.11231
Transformed corn plants expressing Cry3Bb.11231 protein were challenged with western corn rootworm (WCR) larvae in both a seedling and 10 inch pot assay. The trans-formed genotype was A634, where the progeny of the R0 cross by A634 was evaluated. Observations included effect on larval development (weight), root damage rating (RDR), and protein expression. The transformation vector containing the cry3Bb gene was pMON33710. Treatments included the positive and negative iso-populations for each event and an A634 check.
The seedling assay consisted of the following steps: (i) single seeds were placed in 1 oz cups containing potting soil; (ii) at spiking, each seedling was infested with 4 neonate larvae; and (iii) after infestation, seedlings were incubated for 7 days at 25° C., 50% RH, and 14:10 (L:D) photo period. Adequate moisture was added to the potting soil during the incubation period to maintain seedling vigor.
The 10 inch pot assay consisted of the following steps: (i) single seeds were placed in 10 inch pots containing potting soil; (ii) at 14 days post planting, each pot was infested with 800 eggs which have been pre-incubated such that hatch would occur 5-7 days post infestation; and (iii) after infestation, plants were incubated for 4 weeks under the same environmental conditions as the seedling assay. Pots were both sub and top irrigated daily.
For the seedling assay, on day 7 plants were given a root damage rating, and surviving larvae were weighed. Also at this time, Cry3Bb protein concentrations in the roots were determined by ELISA. The scale used for the seedling assay to assess root damage is as follows: RDR (root damage rating) 0=no visible feeding; RDR 1=very light feeding; RDR 2=light feeding; RDR 3=moderate feeding; RDR 4=heavy feeding; and RDR 5=very heavy feeding.
Results of the seedling assay are shown in Table 26. Plants expressing Cry3Bb protein were completely protected by WCR feeding, where surviving larvae within this treatment had not grown. Mean larval weights ranged from 2.03-2.73 mg for the nonexpressing treatments, where the surviving larval average weight was 0.11 mg on the expressing cry3Bb treatment. Root damage ratings were 3.86 and 0.33 for the nonexpressing and expressing isopopulations, respectively. Larval survival ranged from 75-85% for the negative and check treatments, where only 25% of the larvae survived on the Cry3Bb treatment.







TABLE 26







EFFECT OF CRY3BB EXPRESSING PLANTS ON


WCR LARVAE IN A SEEDLING ASSAY










Plants
Larvae

















Root


%
Mean ± SD


Event
Treatment
N
(ppm)
RDR ± SD
N
Surv
Wt. (mg)

















16
Negative
7
0.0
3.86 ± 0.65
21
75
2.73 ± 1.67


16
Positive
3
29.01
0.33 ± 0.45
3
25
0.11 ± 0.07


A634
Check
4
0.0
—
13
81
2.03 ± 0.83









For the 10 inch pot assay, at 4 weeks post infestation plant height was recorded and a root damage rating (Iowa 1-6 scale; Hills and Peters, 1971) was given.
Results of the 10 inch pot assay are shown in Table 27. Plants expressing Cry3Bb protein had significantly less feeding damage and were taller than the non-expressing plants. Event 16, the higher of the two expressing events provided nearly complete control. The negative treatments had very high root damage ratings indicating very high insect pressure. The positive mean root damage ratings were 3.4 and 2.2 for event 6 and 16, respectively. Mean RDR for the negative treatment was 5.0 and 5.6.







TABLE 27







EFFECT OF CRY3BB EXPRESSING CORN IN CONTROLLING


WCR LARVAL FEEDING IN A 10 INCH POT ASSAY















Root

Plant


Event
Treatment
N
(ppm)
RDR ± SD
Height (cm)















6
Negative
7
0.0
5.0 ± 1.41
49.7 ± 18.72


6
Positive
5
7.0
3.4 ± 1.14
73.9 ± 8.67


16
Negative
5
0.0
5.6 ± 0.89
61.2 ± 7.75


16
Positive
5
55.0
2.2 ± 0.84
83.8 ± 7.15









In summary, corn plants expressing Cry3Bb protein have a significant biological effect on WCR larval development as seen in the seedling assay. When challenged with very high infestation levels, plants expressing the Cry3Bb protein were protected from WCR larval feeding damage as illustrated in the 10 inch pot assay.
6.0 BRIEF DESCRIPTION OF THE SEQUENCE IDENTIFIERS
SEQ ID NO:1 DNA sequence of cry3Bb.11221 gene.
SEQ ID NO:2 Amino acid sequence of Cry3Bb.11221 polypeptide.
SEQ ID NO:3 DNA sequence of cry3Bb.1222 gene.
SEQ ID NO:4 Amino acid sequence of Cry3Bb.11222 polypeptide.
SEQ ID NO:5 DNA sequence of cry3Bb.11223 gene.
SEQ ID NO:6 Amino acid sequence of Cry3Bb.11223 polypeptide.
SEQ ID NO:7 DNA sequence of cry3Bb.11224 gene.
SEQ ID NO:8 Amino acid sequence of Cry3Bb.11224 polypeptide.
SEQ ID NO:9 DNA sequence of cry3Bb.11225 gene.
SEQ ID NO:10 Amino acid sequence of Cry3Bb.11225 polypeptide.
SEQ ID NO:11 DNA sequence of cry3Bb.11226 gene.
SEQ ID NO:12 Amino acid sequence of Cry3Bb.11226 polypeptide.
SEQ ID NO:13 DNA sequence of cry3Bb.11227 gene.
SEQ ID NO:14 Amino acid sequence of Cry3Bb.11227 polypeptide.
SEQ ID NO:15 DNA sequence of cry3Bb.11228 gene.
SEQ ID NO:16 Amino acid sequence of Cry3Bb.11228 polypeptide.
SEQ ID NO:17 DNA sequence of cry3Bb.11229 gene.
SEQ ID NO:18 Amino acid sequence of Cry3Bb.11229 polypeptide.
SEQ ID NO:19 DNA sequence of cry3Bb.11230 gene.
SEQ ID NO:20 Amino acid sequence of Cry3Bb.11230 polypeptide.
SEQ ID NO:21 DNA sequence of cry3Bb.11231 gene.
SEQ ID NO:22 Amino acid sequence of Cry3Bb.11231 polypeptide.
SEQ ID NO:23 DNA sequence of cry3Bb.11232 gene.
SEQ ID NO:24 Amino acid sequence of Cry3Bb.11232 polypeptide.
SEQ ID NO:25 DNA sequence of cry3Bb.11233 gene.
SEQ ID NO:26 Amino acid sequence of Cry3Bb.11233 polypeptide.
SEQ ID NO:27 DNA sequence of cry3Bb.11234 gene.
SEQ ID NO:28 Amino acid sequence of Cry3Bb.11234 polypeptide.
SEQ ID NO:29 DNA sequence of cry3Bb.11235 gene.
SEQ ID NO:30 Amino acid sequence of Cry3Bb.11235 polypeptide.
SEQ ID NO:31 DNA sequence of cry3Bb.11236 gene.
SEQ ID NO:32 Amino acid sequence of Cry3Bb.11236 polypeptide.
SEQ ID NO:33 DNA sequence of cry3Bb.11237 gene.
SEQ ID NO:34 Amino acid sequence of Cry3Bb.11237 polypeptide.
SEQ ID NO:35 DNA sequence of cry3Bb.11238 gene.
SEQ ID NO:36 Amino acid sequence of Cry3Bb.11238 polypeptide.
SEQ ID NO:37 DNA sequence of cry3Bb.11239 gene.
SEQ ID NO:38 Amino acid sequence of Cry3Bb.11239 polypeptide.
SEQ ID NO:39 DNA sequence of cry3Bb.11241 gene.
SEQ ID NO:40 Amino acid sequence of Cry3Bb.11241 polypeptide.
SEQ ID NO:41 DNA sequence of cry3Bb.11242 gene.
SEQ ID NO:42 Amino acid sequence of Cry3Bb.11242 polypeptide.
SEQ ID NO:43 DNA sequence of cry3Bb.11032 gene.
SEQ ID NO:44 Amino acid sequence of Cry3Bb.11032 polypeptide.
SEQ ID NO:45 DNA sequence of cry3Bb.11035 gene.
SEQ ID NO:46 Amino acid sequence of Cry3Bb.11035 polypeptide.
SEQ ID NO:47 DNA sequence of cry3Bb.11036 gene.
SEQ ID NO:48 Amino acid sequence of Cry3Bb.11036 polypeptide.
SEQ ID NO:49 DNA sequence of cry3Bb.11046 gene.
SEQ ID NO:50 Amino acid sequence of Cry3Bb.11046 polypeptide.
SEQ ID NO:51 DNA sequence of cry3Bb.11048 gene.
SEQ ID NO:52 Amino acid sequence of Cry3Bb.11048 polypeptide.
SEQ ID NO:53 DNA sequence of cry3Bb.1051 gene.
SEQ ID NO:54 Amino acid sequence of Cry3Bb.11051 polypeptide.
SEQ ID NO:55 DNA sequence of cry3Bb.11057 gene.
SEQ ID NO:56 Amino acid sequence of Cry3Bb.11057 polypeptide.
SEQ ID NO:57 DNA sequence of cry3Bb.11058 gene.
SEQ ID NO:58 Amino acid sequence of Cry3Bb.11058 polypeptide.
SEQ ID NO:59 DNA sequence of cry3Bb.11081 gene.
SEQ ID NO:60 Amino acid sequence of Cry3Bb.11081 polypeptide.
SEQ ID NO:61 DNA sequence of cry3Bb.11082 gene.
SEQ ID NO:62 Amino acid sequence of Cry3Bb.11082 polypeptide.
SEQ ID NO:63 DNA sequence of cry3Bb.11083 gene.
SEQ ID NO:64 Amino acid sequence of Cry3Bb.11083 polypeptide.
SEQ ID NO:65 DNA sequence of cry3Bb.11084 gene.
SEQ ID NO:66 Amino acid sequence of Cry3Bb.11084 polypeptide.
SEQ ID NO:67 DNA sequence of cry3Bb.11095 gene.
SEQ ID NO:68 Amino acid sequence of Cry3Bb.11095 polypeptide.
SEQ ID NO:69 DNA sequence of cry3Bb.60 gene.
SEQ ID NO:70 Amino acid sequence of Cry3Bb.60 polypeptide.
SEQ ID NO:71 Primer FW001.
SEQ ID NO:72 Primer FW006.
SEQ ID NO:73 Primer MVT095.
SEQ ID NO:74 Primer MVT097.
SEQ ID NO:75 Primer MVT091.
SEQ ID NO:76 Primer MVT075.
SEQ ID NO:77 Primer MVT076.
SEQ ID NO:78 Primer MVT111.
SEQ ID NO:79 Primer MVT094.
SEQ ID NO:80 Primer MVT103.
SEQ ID NO:81 Primer MVT081.
SEQ ID NO:82 Primer MVT085.
SEQ ID NO:83 Primer A.
SEQ ID NO:84 Primer B.
SEQ ID NO:85 Primer C.
SEQ ID NO:86 Primer D.
SEQ ID NO:87 Primer E.
SEQ ID NO:88 Primer F.
SEQ ID NO:89 Primer G.
SEQ ID NO:90 Primer WD112.
SEQ ID NO:91 Primer WD115.
SEQ ID NO:92 Primer MVT105.
SEQ ID NO:93 Primer MVT092.
SEQ ID NO:94 Primer MVT070.
SEQ ID NO:95 Primer MVT083.
SEQ ID NO:96 N-terminal amino acid of Cry3Bb polypeptide.
SEQ ID NO:97 DNA sequence of wild-type cry3Bb gene.
SEQ ID NO:98 Amino acid sequence of wild-type Cry3Bb polypeptide.
SEQ ID NO:99 Plantized DNA sequence for cry3Bb.11231 gene.
SEQ ID NO:100 Amino acid sequence of plantized Cry3Bb.11231 polypeptide.
SEQ ID NO:101 DNA sequence of cry3Bb gene used to prepare SEQ ID NO:99.
SEQ ID NO:102 DNA sequence of wild-type cry3Bb gene, Genbank #M89794.
SEQ ID NO:103 DNA sequence of Oligo #1.
SEQ ID NO:104 DNA sequence of Oligo #2.
SEQ ID NO:105 DNA sequence of Oligo #3.
SEQ ID NO:106 DNA sequence of Oligo #4.
SEQ ID NO:107 DNA sequence of cry3Bb.11098 gene.
SEQ ID NO:108 Amino acid sequence of Cry3Bb.11098 polypeptide.
7.0 REFERENCES
The following references, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated herein by reference.

    U.S. Pat. No. 4,237,224, issued Dec. 2, 1980.
    U.S. Pat. No. 4,332,898, issued Jun. 1, 1982.
    U.S. Pat. No. 4,342,832, issued Aug. 3, 1982.
    U.S. Pat. No. 4,356,270, issued Oct. 26, 1982.
    U.S. Pat. No. 4,362,817, issued Dec. 7, 1982.
    U.S. Pat. No. 4,371,625, issued Feb. 1, 1983.
    U.S. Pat. No. 4,448,885, issued May 15, 1984.
    U.S. Pat. No. 4,467,036, issued Aug. 21, 1984.
    U.S. Pat. No. 4,554,101, issued Nov. 19, 1985.
    U.S. Pat. No. 4,683,195, issued Jul. 28, 1987.
    U.S. Pat. No. 4,683,202, issued Jul. 28, 1987.
    U.S. Pat. No. 4,757,011, issued Jul. 12, 1988.
    U.S. Pat. No. 4,766,203, issued Aug. 23, 1988.
    U.S. Pat. No. 4,769,061, issued Sep. 6, 1988.
    U.S. Pat. No. 4,797,279, issued Jan. 10, 1989.
    U.S. Pat. No. 4,800,159, issued Jan. 24, 1989.
    U.S. Pat. No. 4,883,750, issued Nov. 28, 1989.
    U.S. Pat. No. 4,910,016, issued Mar. 20, 1990.
    U.S. Pat. No. 4,940,835, issued Feb. 23, 1990.
    U.S. Pat. No. 4,965,188, issued Oct. 23, 1990.
    U.S. Pat. No. 4,971,908, issued Nov. 20, 1990.
    U.S. Pat. No. 4,987,071, issued Jan. 22, 1991.
    U.S. Pat. No. 5,380,831, issued Jan. 10, 1995.
    U.S. Pat. No. 5,023,179, issued Jun. 11, 1991.
    U.S. Pat. No. 5,024,837, issued Jun. 18, 1991.
    U.S. Pat. No. 5,126,133, issued Jun. 30, 1992.
    U.S. Pat. No. 5,176,995, issued Oct. 15, 1991.
    U.S. Pat. No. 5,187,091, issued XXXXX, 1993.
    U.S. Pat. No. 5,322,687, issued Jun. 21, 1994.
    U.S. Pat. No. 5,334,711, issued Aug. 2, 1994.
    U.S. Pat. No. 5,378,619, issued Jan. 3, 1995.
    U.S. Pat. No. 5,424,412, issued Jun. 13, 1995.
    U.S. Pat. No. 5,441,884, issued Aug. 15, 1995.
    U.S. Pat. No. 5,463,175, issued Oct. 31, 1995.
    U.S. Pat. No. 5,500,365, issued Mar. 19, 1996.
    U.S. Pat. No. 5,591,616, issued Jan. 7, 1997.
    U.S. Pat. No. 5,631,359, issued May 20, 1997.
    U.S. Pat. No. 5,659,123, issued Aug. 19, 1997.
    Eur. Pat. No. EP 0120516.
    Eur. Pat. No. EP 0360257.
    Eur. Pat. Appl. No. 92110298.4.
    Eur. Pat. Appl. No. 295156A1.
    Great Britain Patent 2202328.
    Int. Pat. Appl. Publ. No. WO 91/03162.
    Int. Pat. Appl. Publ. No. WO 92/07065.
    Int. Pat. Appl. Publ. No. WO 93/15187.
    Int. Pat. Appl. Publ. No. WO 93/23569.
    Int. Pat. Appl. Publ. No. WO 94/02595.
    Int. Pat. Appl. Publ. No. WO 94/13688.
    Intl. Pat. Appl. Publ. No. PCT/US87/00880.
    Intl. Pat. Appl. Publ. No. PCT/US89/01025.
    Intl. Pat. Appl. Publ. No. WO 88/09812.
    Intl. Pat. Appl. Publ. No. WO 88/10315.
    Intl. Pat. Appl. Publ. No. WO 89/06700.
    Intl. Pat. Appl. Publ. No. WO 93/07278.
    Abbott, “A method for computing the effectiveness of an insecticide,” J. Econ. Entomol., 18:265-267, 1925.
    Abdullah et al., Biotechnology, 4:1087, 1986.
    Almond and Dean, Biochemistry, 32:1040-1046, 1993.
    An et al., EMBO J., 4:277-287, 1985.
    Angsuthanasamnbat et al., FEMS Microbiol. Lett.; 111:255-262, 1993.
    Armstrong et al., Plant Cell Rep., 9:335-339, 1990.
    Aronson, Wu, Zhang, “Mutagenesis of specificity and toxicity regions of a Bacillus thuringiensis protoxin gene.” J. Bacteriol., 177:4059-4065, 1995.
    Bagdasarian et al., Gene, 16:237, 1981.
    Baum et al., Appl. Environ. Microbiol., 56:3420-3428, 1990.
    Baum, “Tn5401, a new class II transposable element from Bacillus thuringiensis,” J. Bacteriol., 176:2835-2845, 1994.
    Baum, J. Bacteriol., 177:4036-4042, 1995.
    Baum, Kakefuda, Gawron-Burke, “Engineering Bacillus thuringiensis Bioinsecticides with an Indigenous Site-Specific Recombination System,” Appl. Environ. Microbiol., 62:XXX-XXX 1996.
    Benbrook et al., In: Proceedings Bio Expo 1986, Butterworth, Stoneham, Mass., pp. 27-54, 1986.
    Bevan et al., Nature, 304:184, 1983.
    Bolivar et al., Gene, 2:95, 1977.
    Branden and Tooze, “Introduction to Protein Structure,” Garland Publishing, Inc., New York, N.Y., 1991.
    Brussock and Currier, “Use of sodium dodecyl sulfate-polyacryamide gel electrophoresis to quantify Bacillus thuringiensis δ-endotoxins,” In: “Analytical Chemistry of Bacillus thuringiensis,” L. A. Hickle and W. L. Fitch, (Eds), American Chemical Society, Washington D.C., pp. 78-87, 1990.
    Capecchi, “High efficiency transformation by direct microinjection of DNA into cultured mammalian cells,” Cell, 22(2):479-488, 1980.
    Caramori, Albertini, Galizzi, “In vivo generation of hybrids between two Bacillus thuringiensis insect-toxin-encoding genes,” Gene, 98:37-44, 1991.
    Cashmore et al., Gen. Eng. of Plants, Plenum Press, New York, 29-38, 1983.
    Chambers et al., Appl Environ. Microbiol., 173:3966-3976, 1991.
    Chau et al., Science, 244:174-181, 1989.
    Chen et al., Nucl. Acids Res., 20:4581-9, 1992.
    Chen, Curtiss, Alcantara, Dean, “Mutations in domain I of Bacillus thuringiensis δ-endotoxin CryIAb reduce the irreversible binding of toxin to Manduca sexta brush border membrane vesicles,” J. Biol. Chem., 270:6412-6419, 1995.
    Chen, Lee, Dean, “Site-directed mutations in a highly conserved region of Bacillus thuringiensis δ-endotoxin affect inhibition of short circuit current across Bombyx mori midguts,” Proc. Natl. Acad. Sci. USA, 90:9041-9045, 1993.
    Chowrira and Burke, Nucl. Acids Res., 20:2835-2840, 1992.
    Clapp, “Somatic gene therapy into hematopoietic cells. Current status and future implications,” Clin. Perinatol., 20(1):155-168, 1993.
    Cody, Luft, Jensen, Pangborn English, “Purification and crystallization of insecticidal δ-endotoxin CryIIIB2 from Bacillus thuringiensis,” Proteins: Struct. Funct. Genet., 14:324, 1992.
    Collins and Olive, Biochem., 32:2795-2799, 1993.
    Conway and Wickens, In: RNA Processing, p. 40, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1988.
    Cornelissen et al., “A tobacco mosaic virus-induced tobacco protein is homologous to the sweet-tasting protein thaumatin,” Nature, 321(6069):531-532, 1986.
    Cramer, Cohen, Merrill, Song, “Structure and dynamics of the colicin E1 channel,” Molec. Microbiol., 4:519-526, 1990.
    CRC Handbook of Chemistry and Physics, 58th edition, CRC Press, Inc., Cleveland, Ohio, p. C-769, 1977.
    Cristou et al., Plant Physiol, 87:671-674, 1988.
    Curiel, Agarwal, Wagner, Cotten, “Adenovirus enhancement of transferrin-polylysine-mediated gene delivery,” Proc. Natl. Acad. Sci. USA, 88(19):8850-8854, 1991.
    Curiel, Wagner, Cotten, Birnstiel, Agarwal, Li, Loechel, Hu, “High-efficiency gene transfer mediated by adenovirus coupled to DNA-polylysine complexes,” Hum. Gen. Ther., 3(2):147-154, 1992.
    Daum, “Revision of two computer programs for probit analysis,” Bull. Entomol. Soc. Amer., 16:10-15, 1970.
    De Maagd, Kwa, van der Klei, Yamamoto, Schipper, Vlak, Stiekema, Bosch, “Domain II substitution in Bacillus thuringiensis delta-endotoxin Cry1A(b) results in superior toxicity for Spodoptera exigua and altered membrane protein recognition,” Appl. Environ. Microbiol., 62:1537-1543, 1996.
    Dean et al., Nucl. Acids Res., 14(5):2229, 1986.
    Dhir et al., Plant Cell Reports, 10:97, 1991.
    Diehn et al., Genet. Engineer., 18:83-99, 1996.
    Donovan, Dankocsik, Gilbert, Groat, Gawron-Burke, Carlton, “The P2 protein of Bacillus thuringiensis var. kurstaki: nucleotide sequence and entomocidal activity,” J. Biol. Chem., 263:561-567, 1988.
    Doyle et al., J. Biol. Chem., 261(20):9228-9236, 1986.
    Dropulic et al., J. Virol., 66:1432-41, 1992.
    Dunitz, “The entropic cost of bound water in crystals and biomolecules,” Science, 264:670-68x, 1994.
    Earp and Ellar, Nucl. Acids Res., 15:3619, 1987.
    Eglitis and Anderson, “Retroviral vectors for introduction of genes into mammalian cells,” Biotechniques, 6(7):608-614, 1988.
    Eglitis, Kantoff, Kohn, Karson, Moen, Lothrop, Blaese, Anderson, “Retroviral-mediated gene transfer into hemopoietic cells,” Adv. Exp. Med. Biol., 241:19-27, 1988.
    Elroy-Stein and Moss, Proc. Natl. Acad. Sci. USA, 87:6743-7, 1990.
    English and Slatin, Insect Biochem. Mol. Biol., 22:1-7, 1992.
    English, Readdy, Bastian, “Delta-endotoxin-induced leakage of 86Rb+—K+ and H2O from phospholipid vesicles is catalyzed by reconstituted midgut membrane,” Insect Biochem., 21:177-184, 1991.
    Fischhoff et al., Bio/Technology, 5:807-813, 1987.
    Fraley et al., Bio/Technology, 3:629-635, 1985.
    Fraley et al., Proc. Natl. Acad. Sci. USA, 80:4803, 1983.
    Frohman, PCRTM Protocols, a Guide to Methods and Applications XVIII Ed., Academic Press, New York, 1990.
    Fromm et al., Bio/Technology, 8:833-839, 1990.
    Fromm et al., Nature, 319:791-793, 1986.
    Fromm, Taylor, Walbot, “Expression of genes transferred into monocot and dicot plant cells by electroporation,” Proc. Natl. Acad. Sci. USA, 82(17):5824-5828, 1985.
    Fujimura et al., Plant Tissue Cult. Lett., 2:74, 1985.
    Fynan, Webster, Fuller, Haynes, Santoro, Robinson, “DNA vaccines: protective immunizations by parenteral, mucosal, and gene gun inoculations,” Proc. Natl. Acad. Sci. USA, 90(24):11478-11482, 1993.
    Galitsky, Cody, Wojtczak, Ghosh, Luft, Pangbom, Wawrzak, English, “Crystal and Molecular Structure of the Insecticidal Bacterial δ-Endotoxin CryIIIB2 of Bacillus thuringiensis,” Research Communication to Ecogen Inc., Langhorne, Pa., 1993.
    Gao and Huang, Nucl. Acids Res., 21:2867-72, 1993.
    Gazit and Shai, “Structural and Functional Characterization of the α-5 segment of Bacillus thuringiensis δ-endotoxin,” Biochemistry, 32:3429-3436, 1993.
    Gazit and Shai, “The assembly and organization of the α-5 and α7 helices from the pore-forming domain of Bacillus thuringiensis δ-endotoxin,” J. Biol. Chem., 270:2571-2578, 1995.
    Ge, Rivers, Milne, Dean, “Functional domains of Bacillus thuringiensis insecticidal crystal proteins: refinement of Heliothis virescens and Trichoplusia ni specificity domains on CryIA(c),” J. Biol. Chem., 266:17954-17958, 1991.
    Genovese and Milcarek, In: RNA Processing, p. 62, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1988.
    Gil and Proudfoot, Nature, 312:473, 1984.
    Gonzalez Jr. et al., Proc. Natl. Acad. Sci USA, 79:6951-6955, 1982.
    Graham and van der Eb, “Transformation of rat cells by DNA of human adenovirus 5,” Virology, 54(2):536-539, 1973.
    Grochulski, Masson, Borisova, Pusztai-Carey, Schwartz, Brousseau, Cygler, “Bacillus thuringiensis CryIA(a) insecticidal toxin: crystal structure and channel formation,” J. Mol. Biol., 254:447-464, 1995.
    Guerrier-Takada et al., Cell, 35:849, 1983.
    Hampel and Tritz, Biochem., 28:4929, 1989.
    Hampel et al., Nucl. Acids Res., 18:299, 1990.
    Harlow and Lane, “Antibodies: A Laboratory Manual,” Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1988.
    Herrera-Estrella et al., Nature, 303:209, 1983.
    Hertel et al., Nucl. Acids Res., 20:3252, 1992.
    Hertig et al., Plant Mol. Biol., 16:171-174, 1991.
    Hess, Intern Rev. Cytol., 107:367, 1987.
    Hills and Peters, J. Econ. Entomol, 64:764-765, 1971.
    Hockema, In: The Binary Plant Vector System, Offset-durkkerij, Kanters B. V., Alblasserdam, Chapter 5.
    Höfte and Whitely, Microbiol. Rev., 53:242-255, 1989.
    Holland et al., Biochemistry, 17:4900, 1978.
    Holsters et al., Mol. Gen. Genet., 163:181-187, 1978.
    Honee, van der Salm, Visser, Nucl. Acids Res., 16:6240, 1988.
    Horsch et al., Science, 227:1229-1231, 1985.
    Humason, In: Animal Tissue Techniques, W.H. Freeman and Company, 1967.
    Jaeger et al., Proc. Natl. Acad. Sci. USA, 86: 7706-7710, 1989.
    Johnston and Tang, “Gene gun transfection of animal cells and genetic immunization,” Methods Cell. Biol., 43(A):353-365, 1994.
    Jorgensen et al., Mol. Gen. Genet., 207:471, 1987.
    Kaiser and Kezdy, Science, 223:249-255, 1984.
    Kashani-Saber et al., Antisense Res. Dev., 2:3-15, 1992.
    Keller et al., EMBO J., 8:1309-14, 1989.
    Klee et al., Bio/Technology, 3:637-642, 1985.
    Klein et al., Nature, 327:70, 1987.
    Klein et al., Proc. Natl. Acad. Sci. USA, 85:8502-8505, 1988.
    Kozak, Nature, 308:241-246, 1984.
    Krieg et al., Anzeiger fur Schadlingskunde Pflanzenschutz Umweltschutz, 57:145-150, 1984.
    Krieg et al., Z. ang Ent., 96:500-508, 1983.
    Kuby, Immunology 2nd Edition, W.H. Freeman & Company, NY, 1994
    Kunkle, “Rapid and efficient site-specific mutagenesis without phenotypic selection,” Proc. Natl. Acad. Sci. USA, 82:488-492, 1985.
    Kunkle, Roberts, Zabour, Methods Enzymol., 154:367-382, 1987.
    Kwak, Lu, Dean, “Exploration of receptor binding of Bacillus thuringiensis toxins,” Mem. Inst. Oswaldo, 90:75-79, 1995.
    Kwoh et al., Proc. Natl. Acad. Sci. USA, 86(4):1173-1177, 1989.
    Kyte and Doolittle, J. Mol. Biol., 157:105-132, 1982.
    L'Huillier et al., EMBO J., 11:4411-8, 1992.
    LaBean and Kauffman, “Design of synthetic gene libraries encoding random sequence proteins with desired ensemble characteristics,” Prot. Sci., 2:1249-1254, 1993.
    Lambert, Buysse, Decock, Jansens, Piens, Saey, Seurinck, Van Audenhove, Van Rie, Van Vliet, Peferoen, “A Bacillus thuringiensis insecticidal crystal protein with a high activity against members of the family Noctuidae,” Appl. Environ. Microbiol., 62:80-86, 1996.
    Lee, Milne, Ge, Dean, “Location of a Bombyx mori receptor binding region on a Bacillus thuringiensis δ-endotoxin,” J. Biol. Chem., 267:3115-3121, 1992.
    Lee, Young, Dean, “Domain III exchanges of Bacillus thuringiensis CryIA toxins affect binding to different gypsy moth midgut receptors,” Biochem. Biophys. Res. Commun., 216:306-312, 1995.
    Li, Carroll, Ellar, “Crystal structure of insecticidal δ-endotoxin from Bacillus thuringiensis at 2.5 Å resolution,” Nature (London), 353:815-821, 1991.
    Lieber et al., Methods Enzymol., 217:47-66, 1993.
    Lindstrom et al., Developmental Genetics, 11:160, 1990.
    Lisziewicz et al., Proc. Natl. Acad. Sci. U.S.A. 90:8000-4, 1993.
    Lorz et al., Mol. Gen. Genet., 199:178, 1985.
    Lu, Rajamohan, Dean, “Identification of amino acid residues of Bacillus thuringiensis δ-endotoxin CryIAa associated with membrane binding and toxicity to Bombyx mori,” J. Bacteriol., 176:5554-5559, 1994.
    Lu, Xiao, Clapp, Li, Broxmeyer, “High efficiency retroviral mediated gene transduction into single isolated immature and replatable CD34(3+) hematopoietic stem/progenitor cells from human umbilical cord blood,” J. Exp. Med., 178(6):2089-2096, 1993.
    Macaluso and Mettus, J. Bacteriol., 173:1353-1356, 1991.
    Maddock et al., Third International Congress of Plant Molecular Biology, Abstract 372, 1991.
    Maloy et al., “Microbial Genetics” 2nd Edition. Jones and Bartlett Publishers, Boston, Mass., 1994.
    Maloy, “Experimental Techniques in Bacterial Genetics” Jones and Bartlett Publishers, Boston, Mass., 1990.
    Maniatis, Fritsch, Sambrook, In: Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1982.
    Marcotte et al., Nature, 335:454, 1988.
    McDevitt et al., Cell, 37:993-999, 1984.
    McElroy et al., Plant Cell, 2:163-171, 1990.
    Mettus and Macaluso, Appl. Environ. Microbiol., 56:1128-1134, 1990.
    Michael, “Mutagenesis by Incorporation of a Phosphorylated Oligo During PCRTM Amplification,” BioTechniques, 16(3):410-412, 1994.
    Neuhaus et al., Theor. Appl. Genet., 75:30, 1987.
    Odell et al., Nature, 313:810, 1985.
    Ohara et al., Proc. Natl. Acad. Sci. USA, 86(15):5673-5677, 1989.
    Ohkawa et al., Nucl. Acids Symp. Ser., 27:15-6, 1992.
    Ojwang et al., Proc. Natl. Acad. Sci. USA, 89:10802-6, 1992.
    Olson et al., J. Bacteriol., 150:6069, 1982.
    Omirulleh et al., Plant Molecular Biology, 21:415-428, 1993.
    Pandey and Marzluff, In “RNA Processing,” p. 133, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1987.
    Pena et al., Nature, 325:274, 1987.
    Perrault et al., Nature, 344:565, 1990.
    Perrotta and Been, Biochem., 31:16, 1992.
    Pieken et al., Science, 253:314, 1991.
    Poszkowski et al., EMBO J., 3:2719, 1989.
    Potrykus et al., Mol. Gen. Genet., 199:183, 1985.
    Poulsen et al., Mol. Gen. Genet., 205:193-200, 1986.
    Prokop and Bajpai, “Recombinant DNA Technology I,” Ann. N.Y. Acad. Sci., 646:xxx-xxx, 1991.
    Rajamohan, Alcantara, Lee, Chen, Curtiss, Dean, “Single amino acid changes in domain II of Bacillus thuringiensis CryIAb δ-endotoxin affect irreversible binding to Manduca sexta midgut membrane vesicles,” J. Bacteriol., 177:2276-2282, 1995.
    Rajamohan, Cotrill, Gould, Dean, “Role of domain II, loop 2 residues of Bacillus thuringiensis CryIAb δ-endotoxin in reversible and irreversible binding to Manduca sexta and Heliothis virescens,” J. Biol. Chem., 271:2390-2397, 1996.
    Rogers et al., In: Methods For Plant Molecular Biology, A. Weissbach and H. Weissbach, eds., Academic Press Inc., San Diego, Calif. 1988.
    Rogers et al., Methods Enzymol., 153:253-277, 1987.
    Rossi et al., Aids Res. Hum. Retrovir., 8:183, 1992.
    Sadofsky and Alwine, Molec. Cell. Biol., 4(8): 1460-1468, 1984.
    Sambrook et al., “Molecular Cloning: A Laboratory Manual,” Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1989.
    Sanchis, Lereclus, Menou, Chaufaux, Guo, Lecadet, Mol. Microbiol., 3:229-238, 1989.
    Sanchis, Lereclus, Menou, Chaufaux, Lecadet, Mol. Microbiol., 2:393-404, 1988.
    Sarver et al., Science, 247:1222-1225, 1990.
    Saville and Collins, Cell, 61:685-696, 1990.
    Saville and Collins, Proc. Natl. Acad. Sci. USA, 88:8826-8830, 1991.
    Scanlon et al., Proc. Natl. Acad. Sci. USA, 88:10591-5, 1991.
    Scaringe et al., Nucl. Acids Res., 18:5433-5441, 1990.
    Schnepf and Whitely, Proc. Natl. Acad. Sci. USA, 78:2893-2897, 1981.
    Schnepf et al., J. Biol. Chem., 260:6264-6272, 1985.
    Segal, “Biochemical Calculations” 2nd Edition, John Wiley & Sons, New York, 1976.
    Shaw and Kamen, Cell, 46:659-667, 1986.
    Shaw and Kamen, In: “RNA Processing”, p. 220, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1987.
    Simpson, Science, 233:34, 1986.
    Slaney, Robbins, English, “Mode of action of Bacillus thuringiensis toxin CryIIIA: An analysis of toxicity in Leptinotarsa decemlineata (Say) and Diabrotica undecimpunciata howardi Barber,” Insect Biochem. Molec. Biol., 22:9-18, 1992.
    Slatin, Abrams, English, “Delta-endotoxins form cation-selective channels in planar lipid bilayers,” Biochem. Biophys. Res. Comm., 169(2):765-772, 1990.
    Smedley and Ellar, “Mutagenesis of three surface-exposed loops of a Bacillus thuringiensis insecticidal toxin reveals residues important for toxicity, receptor recognition and possibly membrane insertion,” Microbiology, 142:1617-1624, 1996.
    Smith and Ellar, “Mutagenesis of two surface-exposed loops of the Bacillus thuringiensis Cry1C δ-endotoxin affects insecticidal specificity,” Biochem. J., 302:611-616, 1994.
    Smith, Merrick, Bone, Ellar, Appl. Environ. Microbiol., 62:680-684, 1996.
    Spielmann et al., Mol. Gen. Genet., 205:34, 1986.
    Stemmer and Morris, “Enzymatic Inverse PCRTM: A Restriction Site Independent, Single-Fragment Method for High-Efficiency, Site-Directed Mutagenesis,” BioTechniques, 13(2):214-220, 1992.
    Stemmer, Proc. Natl. Acad. Sci. USA, 91:10747-1075, 1994.
    Taira et al., Nucl. Acids Res., 19:5125-30, 1991.
    Tomic et al., Nucl. Acids Res., 12:1656, 1990.
    Tomic, Sunjevaric, Savtchenko, Blumenberg, “A rapid and simple method for introducing specific mutations into any position of DNA leaving all other positions unaltered,” Nucleic Acids Res., 18(6):1656, 1990.
    Toriyama et al., Theor Appl. Genet., 73:16, 1986.
    Uchimiya et al., Mol. Gen. Genet, 204:204, 1986.
    Upender et al., Biotechniques, 18:29-31, 1995.
    Usman and Cedergren, TIBS, 17:34, 1992.
    Usman and Cedergren, Trends in Biochem. Sci., 17:334, 1992.
    Usman et al., J. Am. Chem. Soc., 109:7845-7854, 1987.
    Vallette, Merge, Reiss, Adesnik, “Construction of mutant and chimeric genes using the polymerase chain reaction,” Nucl Acids Res., 17:723-733, 1989.
    Vasil et al., “Herbicide-resistant fertile transgenic wheat plants obtained by microprojectile bombardment of regenerable embryogenic callus,” Biotechnology, 10:667-674, 1992.
    Vasil, Biotechnology, 6:397, 1988.
    Velten and Schell, Nucl. Acids Res., 13:6981-6998, 1985.
    Velten et al., EMBO J., 3:2723-2730, 1984.
    Ventura et al., Nucl. Acids Res., 21:3249-55, 1993.
    Vodkin et al., Cell, 34:1023, 1983.
    Vogel et al., J. Cell Biochem., Suppl. 13D:312, 1989.
    Von Tersch, Slatin, Kulesza, English, “Membrane permeabilizing activity of Bacillus thuringiensis Coleopteran-active toxins CryIIIB2 and CryIITTB2 domain 1 peptides,” Appl. Env Microbiol., 60:3711-3717, 1994.
    Wagner, Zatloukal, Cotten, Kirlappos, Mechtler, Curiel, Birnstiel, “Coupling of adenovirus to transferrin-polylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes,” Proc. Natl. Acad. Sci. USA, 89(13):6099-6103, 1992.
    Walker et al., Proc. Natl. Acad. Sci. USA, 89(1):392-396, 1992.
    Walters et al., Biochem. Biophys. Res. Commun., 196:921-926, 1993.
    Watson et al., Molecular Biology of the Gene, 4th Ed., W. A. Benjamin, Inc., Menlo Park, Calif., 1987.
    Weerasinghe et al., J. Virol., 65:5531-4, 1991.
    Weissbach and Weissbach, Methods for Plant Molecular Biology, (eds.), Academic Press, Inc., San Diego, Calif., 1988.
    Wenzler et al., Plant Mol. Biol., 12:41-50, 1989.
    Wickens and Stephenson, Science, 226:1045, 1984.
    Wickens et al., In: “RNA Processing,” p. 9, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., 1987.
    Wolfersberger et al., Appl. Environ. Microbiol., 62:279-282, 1996.
    Wong and Neumann, “Electric field mediated gene transfer,” Biochim. Biophys. Res. Commun., 107(2):584-587, 1982.
    Woolf et al., Proc. Natl. Acad. Sci. USA, 89:7305-7309, 1992.
    Wu and Aronson, “Localized mutagenesis defines regions of the Bacillus thuringiensis δ-endotoxin involved in toxicity and specificity,” J. Biol. Chem., 267:2311-2317, 1992.
    Wu and Dean, “Functional significance of loops in the receptor binding domain of Bacillus thuringiensis CryIIIA δ-endotoxin,” J. Mol. Biol., 255:628-640, 1996.
    Yamada et al., Plant Cell Rep., 4:85, 1986.
    Yang et al., Proc. Natl. Acad. Sci. USA, 87:4144-48, 1990.
    Yu et al., Proc. Natl. Acad. Sci. USA, 90:6340-4, 1993.
    Zatloukal, Wagner, Cotten, Phillips, Plank, Steinlein, Curiel, Birnstiel, “Transferrinfection: a highly efficient way to express gene constructs in eukaryotic cells,” Ann. N.Y. Acad. Sci., 660:136-153, 1992.
    Zhang and Matthews, “Conservations of solvent-binding sites in 10 crystal forms of T4 lysozyme,” Prot. Sci, 3:1031-1039, 1994.
    Zhou et al., Mol. Cell Biol., 10:4529-37, 1990.


All of the compositions and methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.












9.0 APPENDIX


9.1 CRYSTAL COORDINATES OF CRY3BB


HEADER TOXIN 01 −DEC −94


COMPND DELTA−ENDOTOXIN CRYIIIB2


SOURCE (BACILLUS THURINGIENSIS. SUBSPECIES KUMAMOTOENSIS)


AUTHOR N.GALITSKY. V.CODY


REVDAT 1 01−DEC−94


REMARK 1


REMARK 1 REFERENCE 1


REMARK 1 AUTH NIKOLAI GALITSKY. VIVIAN CODY. ANDREZEJ WOJTCZAK.


REMARKS 1 AUTH DEBASHIS GHOSH. JOSEPH R. LUFT. WALTER PANGBORN.


REMARKS 1 AUTH ZEZISLAW WAWRZAK AND LEIGH ENGLISH.


REMARK 1 TITL CRYSTAL AND MOLECULAR STRUCTURE OF THE BACTERIRIAL


REMARK 1 TITL 2 DELTA−ENDOTOXIN CRYIIIB2.


REMARK 1 REF


REMARK 1 REFN


REMARK 1 REFERENCE 2


REMARK 1 AUTH CODY. V.. LUFT. J−R.. JENSEN. E.. PANGBORG. W.. &


REMARKS 1 AUTH ENGLISH .L.


REMARK 1 TITL PURIFICATION AND CRYSTALLIZATION OF INSECTICIDAL


REMARKS 1 TITL 1 DELTA−ENDOTOXIN CRYIIIB2 FROM BACILLUS THURINGIENSIS


REMARK 1 REF PROTEINS: STRUC.FUNC.GENETICS. (1992).14.324.


REMARK 2


REMARK 2


REMARK 2 RESOLUTION. 2.4 ANGSTROMS.


REMARK 3


REMARK 3


REMARK 3 REFINEMENT.


REMARK 3 PROGRAM X−PLOR


REMARK 3 AUTHORS BRUNGER


REMARK 3 A VALUE 0.18


REMARK 3 RFREE VALUE 0.253


REMARK 3 RMSD BOND DISTANCES 0.009 ANGSTROMS


REMARK 3 RMSD BOND ANGLES 1.30 DEGREES


REMARK 3


REMARK 3 NUMBER OF REFLECTIONS 29069


REMARK 3 RESOLUTION RANGE 8.0 −2.4 ANGSTROMS


REMARK 3 DATA CUTOFF 2.0 SIGMA(F)


REMARK 3


REMARK 3 NUMBER OF PROTEIN ATOMS 4750


REMARK 3 NUMBER OF SOLVENT ATOMS 251


REMARK 3


REMARK 3 THE ATOMIC MODEL INCLUDES RESIDUES 64 −652 OF THE PROTEIN


REMARK 3 AND 251 BOUND WATER MOLECULES.


REMARK 3


REMARK 4


REMARK 4 Bacillus thuringiensis (Bt) is a gram−positive soil


REMARK 4 bacterium characterized by its ability to produce


REMARK 4 crystalline inclusions during sporulation which consist of


REMARK 4 proteins exhibiting a highly specific insecticidal activity.


REMARK 4 There are a variety of toxins present in Bt which have


REMARK 4 different charactistics. for example. a−exotoxin


REMARK 4 (phospholipase C. and d−endotoxin (the crystal protein).


REMARK 4


REMARK 5


REMARK 6 REMARK 6 HERE RESULTED FROM LAST REFINEMENT.


REMARK 6 R=18.0%. Rfree=24.3% by X−PLOR


REMARK 6


SEQRES 1 ASP ALA VAL GLY THR GLY ILE SER VAL VAL GLY GLN ILE


SEQRES 2 LEU GLY VAL VAL GLY VAL PRO PHE ALA GLY ALA LEU THR


SEQRES 3 SER PHE TYR GLN SER PHE LEU ASN THR ILE TRP PRO SER


SEQRES 4 ASP ALA ASP PRO TRP LYS ALA PHE MET ALA GLN VAL GLU


SEQRES 5 VAL LEU ILE ASP LYS LYS ILE GLU GLU TYR ALA LYS SER


SEQRES 6 LYS ALA LEU ALA GLU LEU GLN GLY LEU GLN ASN ASN PHE


SEQRES 7 GLU ASP TYR TYR VAL ASN VAL LEU ASN TRP LYS LYS THR


SEQRES 8 PRO LEU SER LEU ARG SER LYS ARG SEE GLN ASP ARG ILE


SEQRES 9 ARG GLU LEU PHE SER GLN ALA GLU SEE HIS PHE PHE ARG


SEQRES 10 ASN SER MET PRO SER PHE ALA VAL SER LYS PHE GLU VAL


SEQRES 11 LEU PHE LEU PRO THR TYR ALA GLN ALA ALA ASN THR HIS


SEQRES 12 LEU LEU LEU LEU LYS ASP ALA GLN VAL PHE GLY GLU GLU


SEQRES 13 TRP GLY TYR SER SER GLU ASP VAL ALA GLU PHE TYR HIS


SEQRES 14 ARG GLN LEU LYS LEU THR GLN GLN TYR THR ASP HIS CYS


SEQRES 15 VAL ASP TRP TYR ASN VAL GLY LEU ASN GLY LEU ARG GLY


SEQRES 16 SER THR TYR ASP ALA TRP VAL LYS PHE ASN ARG PHE ARG


SEQRES 17 ARG GLU MET THR LEU THR VAL LEU ASP LEU ILE VAL LEU


SEORES 18 PHE PRO PHE TYR ASP ILE ARG LEU TYR SER LYS GLY VAL


SEQRES 19 LYS THR GLU LEU THR ARG ASP ILE PHE THR ASP PRO ILE


SEQRES 20 PHE SER ILE ASN THR LEU GLN GLU TYR GLY PRO THR PHE


SEQRES 21 LEU SER ILE GLU ASN SER ILE ARG LYS PRO HIS LEU PHE


SEQRES 22 ASP TYR LEU GLN GLY ILE GLU PHE THR ARG LEU GLN PRO


SEQRES 23 GLY TYR PHE GLY LYS ASP SER PHE ASN TYR TRP SER GLY


SEQRES 24 ASN TYR VAL GLU THR ARG PRO SER TLB GLY SER SER LYS


SEQRES 25 THR ILE THR SER PRO PHE TYR GLY ASP LYS SER THR GLU


SEQRES 26 PRO VAL GLN LYS LEU SER PHE ASP GLY GLN LYS VAL TYR


SEQRES 27 ARG THR ILE ALA ASN THR ASP VAL ALA ALA TRP PRO ASN


SEQRES 28 GLY LYS VAL TYR LEU GLY VAL THR LYS VAL ASP PHE SER


SEQRES 29 GLN TYR ASP ASP GLN LYS ASN GLU THR SER THR GLN THR


SEQRES 30 TYR ASP SER LYS ARG ASN ASN GLY HIS VAL SER ALA GLN


SEQRES 31 ASP SER ILE ASP GLN LEU PRO PRO GLU THR THR ASP GLU


SEQRES 32 PRO LEU GLU LYS ALA TYR SER HIS GLN LEU ASN TYR ALA


SEQRES 33 GLU CYS PHE LEU MET GLN ASP ARG ARG GLY THR ILE PRO


SEORES 34 PHE PHE THR TRP THR HIS ARG SER VAL ASP PHE PHE ASN


SEQRES 35 THR ILE ASP ALA GLU LYS ILE THR GLN LEU PRO VAL VAL


SEQRES 36 LYS ALA TYR ALA LEU SER SER GLY ALA SER ILE ILE GLU


SEQRES 37 GLY PRO GLY PHE THR GLY GLY ASN LEU LEU PHE LEU LYS


SEQRES 38 GLU SER SER ASN SER ILE ALA LYS PHE LYS VAL THR LEU


SEQRES 39 ASN SER ALA ALA LEU LEU GLN ARG TYR ARG VAL ARG ILE


SEQRES 40 ARG TYR ALA SER THR THR ASN LEU ARG LEU PHE VAL GLN


SEQRES 41 ASN SER ASN ASN ASP PHE LEU VAL ILE TYR ILE ASN LYS


SEQRES 42 THR MET ASN LYS ASP ASP ASP LEU THR TYR GLN THR PHE


SEQRES 43 ASP LEU ALA THR THR ASN SER ASN MET GLY PHE SER GLY


SEQRES 44 ASP LYS ASN GLU LEU ILE ILE GLY ALA GLU SER PHE VAL


SEQRES 45 SER ASN GLU LYS ILE TYR ILE ASP LYS ILE GLU PHE ILE


SEQRES 46 PRO VAL GLN LEU


CRYST1 122.440 131.810 105.370 90.00 90.00 90.00 C 2 2 21 6


ORIGX1 1.000000 0.000000 0.000000 0.00000


ORIGX2 0.000000 1.000000 0.000000 0.00000


ORIGX3 0.000000 0.000000 1.000000 0.00000


SCALE1 0.00817 0.00000 0.000000 0.00000


SCALE2 0.00000 0.00759 0.00000 0.00000


SCALE3 0.00000 0.00000 0.00949 0.00000



















ATOM
1
CB
ASP
64
38.002
27.615
24.114
1.00
41.41


ATOM
2
CG
ASP
64
36.543
27.914
23.755
1.00
52.75


ATOM
3
OD1
ASP
64
35.629
27.527
24.530
1.00
57.53


ATOM
4
OD2
ASP
64
36.313
28.570
22.707
1.00
55.49


ATOM
5
C
ASP
64
38.189
25.132
23.609
1.00
31.24


ATOM
6
O
ASP
64
39.200
24.940
22.931
1.00
32.62


ATOM
7
N
ASP
64
39.547
26.161
25.357
1.00
28.94


ATOM
8
CA
ASP
64
38.204
26.213
24.712
1.00
33.24


ATOM
9
N
ALA
65
37.061
24.450
23.398
1.00
26.88


ATOM
10
CA
ALA
65
37.015
23.396
22.384
1.00
24.54


ATOM
11
CB
ALA
65
35.695
22.650
22.456
1.00
25.47


ATOM
12
C
ALA
65
37.289
23.923
20.965
1.00
24.59


ATOM
13
O
ALA
65
38.208
23.470
20.298
1.00
28.06


ATOM
14
N
VAL
66
36.549
24.933
20.533
1.00
24.47


ATOM
15
CA
VAL
66
36.756
25.504
19.203
1.00
23.48


ATOM
16
CB
VAL
66
35.728
26.617
18.903
1.00
21.61


ATOM
17
CG1
VAL
66
36.030
27.331
17.611
1.00
22.39


ATOM
18
CG2
VAL
66
34.351
25.996
18.820
1.00
26.75


ATOM
19
C
VAL
66
38.187
26.004
19.045
1.00
19.98


ATOM
20
O
VAL
66
38.833
25.670
18.077
1.00
23.77


ATOM
21
N
GLY
67
38.713
26.713
20.034
1.00
21.48


ATOM
22
CA
GLY
67
40.081
27.219
19.954
1.00
20.29


ATOM
23
C
GLY
67
41.138
26.133
19.879
1.00
24.27


ATOM
24
O
GLY
67
42.192
26.309
19.265
1.00
23.94


ATOM
25
N
THR
68
40.866
25.002
20.515
1.00
24.20


ATOM
26
CA
THR
68
41.799
23.896
20.492
1.00
24.14


ATOM
27
CB
THR
68
41.461
22.851
21.597
1.00
23.58


ATOM
28
OG1
THR
68
41.688
23.440
22.875
1.00
31.21


ATOM
29
CG2
THR
GB
42.340
21.613
21.503
1.00
27.97


ATOM
30
C
THR
68
41.694
23.304
19.103
1.00
20.97


ATOM
31
O
THR
68
42.705
23.072
18.454
1.00
21.45


ATOM
32
N
GLY
69
40.461
23.174
18.618
1.00
19.58


ATOM
33
CA
GLY
69
40.215
22.672
17.293
1.00
19.83


ATOM
34
C
GLY
69
40.958
23.401
16.229
1.00
21.30


ATOM
35
O
GLY
69
41.668
22.836
15.387
1.00
27.17


ATOM
36
N
ILE
70
40.803
24.714
16.292
1.00
17.89


ATOM
37
CA
ILE
70
41.439
25.637
15.380
1.00
14.96


ATOM
38
CB
ILE
70
40.985
27.081
15.669
1.00
10.04


ATOM
39
CG2
ILE
70
41.955
28.068
15.070
1.00
12.80


ATOM
40
CG1
ILE
70
39.577
27.287
15.087
1.00
17.46


ATOM
41
CD1
ILE
70
38.902
28.609
15.424
1.00
11.32


ATOM
42
C
ILE
70
42.941
25.539
15.476
1.00
15.70


ATOM
43
O
ILE
70
43.620
25.618
14.480
1.00
14.84


ATOM
44
N
SER
71
43.456
25.322
16.675
1.00
20.78


ATOM
45
CA
SER
71
44.886
25.235
16.865
1.00
21.23


ATOM
46
CB
SER
71
45.203
25.328
18.342
1.00
27.06


ATOM
47
OG
SER
71
46.602
25.359
18.562
1.00
38.25


ATOM
48
C
SER
71
45.472
23.958
16.271
1.00
21.51


ATOM
49
O
SER
71
46.528
23.993
15.634
1.00
25.89


ATOM
50
N
VAL
72
44.800
22.835
16.494
1.00
22.02


ATOM
51
CA
VAL
72
45.234
21.543
15.966
1.00
21.27


ATOM
52
CD
VAL
72
44.307
20.400
16.439
1.00
18.56


ATOM
53
CG1
VAL
72
44.732
19.096
15.847
1.00
23.45


ATOM
54
CG2
VAL
72
44.350
20.282
17.908
1.00
24.48


ATOM
55
C
VAL
72
45.230
21.580
14.431
1.00
22.84


ATOM
56
O
VAL
72
46.224
21.210
13.806
1.00
26.65


ATOM
57
N
VAL
73
44.127
22.028
13.822
1.00
19.72


ATOM
58
CA
VAL
73
44.050
22.105
12.359
1.00
20.44


ATOM
59
CB
VAL
73
42.619
22.492
11.872
1.00
20.13


ATOM
60
CG1
VAL
73
42.619
22.896
10.378
1.00
13.81


ATOM
61
CG2
VAL
73
41.680
21.308
12.095
1.00
18.37


ATOM
62
C
VAL
73
45.152
22.995
11.752
1.00
20.22


ATOM
63
O
VAL
73
45.557
22.797
10.615
1.00
24.33


ATOM
64
N
GLY
74
45.663
23.939
12.532
1.00
21.00


ATOM
65
CA
GLY
74
46.743
24.784
12.072
1.00
16.98


ATOM
66
C
GLY
74
48.049
24.028
12.226
1.00
20.80


ATOM
67
O
GLY
74
48.950
24.221
11.434
1.00
23.14


ATOM
68
N
GLN
75
48.183
23.179
13.247
1.00
22.46


ATOM
69
CA
GLN
75
49.438
22.410
13.434
1.00
25.26


ATOM
70
CB
GLN
75
49.561
21.810
14.856
1.00
27.10


ATOM
71
CG
GLN
75
49.713
22.859
15.996
1.00
29.45


ATOM
72
CD
GLN
75
50.044
22.259
17.361
1.00
31.13


ATOM
73
OE1
GLN
75
51.122
21.706
17.557
1.00
40.11


ATOM
74
NE2
GLN
75
49.140
22.408
18.320
1.00
30.96


ATOM
75
C
GLN
75
49.566
21.308
12.389
1.00
24.92


ATOM
76
O
GLN
75
50.629
21.109
11.793
1.00
26.68


ATOM
77
N
ILE
76
48.466
20.601
12.159
1.00
23.54


ATOM
78
CA
ILE
76
48.432
19.541
11.174
1.00
23.61


ATOM
79
CB
ILE
76
47.092
18.760
11.249
1.00
22.99


ATOM
80
CG2
ILE
76
47.186
17.503
10.408
1.00
26.43


ATOM
81
CG1
ILE
76
46.744
18.375
12.700
1.00
19.22


ATOM
82
CD1
ILE
76
47.392
17.129
13.202
1.00
12.10


ATOM
83
C
ILE
76
48.659
20.118
9.733
1.00
24.28


ATOM
84
O
ILE
76
49.445
19.557
8.968
1.00
25.09


ATOM
85
N
LEU
77
48.004
21.224
9.361
1.00
18.82


ATOM
86
CA
LEU
77
48.195
21.810
8.021
1.00
19.38


ATOM
87
CB
LEU
77
47.438
23.142
7.864
1.00
19.61


ATOM
88
CG
LEU
77
46.056
23.261
7.195
1.00
17.45


ATOM
89
CD1
LEU
77
45.474
24.653
7.434
1.00
13.22


ATOM
90
CD2
LEU
77
46.148
22.973
5.711
1.00
11.85


ATOM
91
C
LEU
77
49.680
22.050
7.762
1.00
23.62


ATOM
92
O
LEU
77
50.181
21.881
6.642
1.00
28.58


ATOM
93
N
GLY
78
50.172
22.474
8.802
1.00
21.75


ATOM
94
CA
GLY
78
51.792
22.711
8.676
1.00
21.63


ATOM
95
C
GLY
78
52.564
21.405
8.563
1.00
25.33


ATOM
96
O
GLY
78
53.384
21.263
7.666
1.00
28.22


ATOM
97
N
VAL
79
52.287
20.443
9.449
1.00
24.06


ATOM
98
CA
VAL
79
52.998
19.164
9.452
1.00
18.58


ATOM
99
CB
VAL
79
52.551
18.244
10.651
1.00
16.10


ATOM
100
CG1
VAL
79
51.241
17.506
10.369
1.00
10.60


ATOM
101
CG2
VAL
79
53.637
17.275
10.986
1.00
9.60


ATOM
102
C
VAL
79
52.856
18.464
8.100
1.00
22.38


ATOM
103
O
VAL
79
53.835
17.989
7.512
1.00
24.19


ATOM
104
N
VAL
80
51.649
18.516
7.563
1.00
19.05


ATOM
105
CA
VAL
80
51.330
17.917
6.289
1.00
19.02


ATOM
106
CB
VAL
80
49.817
18.091
6.073
1.00
16.18


ATOM
107
CG1
VAL
80
49.453
18.035
4.624
1.00
25.56


ATOM
108
CG2
VAL
80
49.123
16.931
6.820
1.00
14.84


ATOM
109
C
VAL
80
52.172
18.488
5.140
1.00
16.87


ATOM
110
O
VAL
80
52.399
17.827
4.140
1.00
20.45


ATOM
111
N
GLY
81
52.668
19.704
5.319
1.00
16.74


ATOM
112
CA
GLY
81
53.499
20.337
4.318
1.00
11.13


ATOM
113
C
GLY
81
54.941
19.919
4.468
1.00
13.55


ATOM
114
O
GLY
81
55.812
20.383
3.738
1.00
16.53


ATOM
115
N
VAL
82
55.200
19.022
5.409
1.00
15.12


ATOM
116
CA
VAL
62
56.556
18.526
5.665
1.00
16.31


ATOM
117
CB
VAL
82
56.861
18.482
7.176
1.00
14.83


ATOM
118
CG1
VAL
82
58.245
17.911
7.438
1.00
14.94


ATOM
119
CG2
VAL
82
56.758
19.879
7.759
1.00
15.19


ATOM
120
C
VAL
82
56.632
17.125
5.094
1.00
14.65


ATOM
121
O
VAL
82
55.702
16.348
5.232
1.00
15.48


ATOM
122
N
PRO
83
57.754
16.762
4.481
1.00
19.00


ATOM
123
CD
PRO
83
58.996
17.501
4.237
1.00
18.29


ATOM
124
CA
PRO
83
57.845
15.418
3.917
1.00
22.61


ATOM
125
CB
PRO
83
59.296
15.336
3.482
1.00
18.37


ATOM
126
CG
PRO
83
59.574
16.726
3.089
1.00
21.28


ATOM
127
C
PRO
83
57.526
14.372
4.953
1.00
24.83


ATOM
128
O
PRO
83
57.892
14.532
6.124
1.00
29.53


ATOM
129
N
PHE
84
56.815
13.335
4.521
1.00
24.14


ATOM
130
CA
PHE
84
56.430
12.238
5.362
1.00
25.82


ATOM
131
CB
PHE
84
57.675
11.577
5.954
1.00
27.96


ATOM
132
CG
PHE
84
58.498
10.908
4.925
1.00
34.74


ATOM
133
CD1
PHE
84
59.878
11.046
4.924
1.00
39.61


ATOM
134
CD2
PHE
84
57.890
10.147
3.937
1.00
35.01


ATOM
135
CE1
PHE
84
60.645
10.431
3.946
1.00
40.72


ATOM
136
CE2
PHE
84
58.638
9.534
2.967
1.00
38.56


ATOM
137
CZ
PHE
84
60.023
9.673
2.964
1.00
40.66


ATOM
138
C
PHE
84
55.520
12.692
6.493
1.00
27.58


ATOM
139
O
PHE
84
55.566
12.154
7.595
1.00
27.77


ATOM
140
N
ALA
85
54.689
13.690
6.204
1.00
29.69


ATOM
141
CA
ALA
85
53.764
14.220
7.193
1.00
24.88


ATOM
142
CB
ALA
85
52.627
13.226
7.437
1.00
21.36


ATOM
143
C
ALA
85
54.515
14.562
8.496
1.00
24.27


ATOM
144
O
ALA
85
54.003
14.356
9.595
1.00
23.70


ATOM
145
N
GLY
86
55.737
15.081
8.338
1.00
22.37


ATOM
146
CA
GLY
86
56.560
15.491
9.465
1.00
20.63


ATOM
147
C
GLY
86
57.025
14.410
10.409
1.00
22.40


ATOM
148
O
GLY
86
51.475
14.705
11.509
1.00
23.81


ATOM
149
N
ALA
87
56.976
13.161
9.965
1.00
24.78


ATOM
150
CA
ALA
87
57.383
12.030
10.789
1.00
23.69


ATOM
151
CB
ALA
87
57.223
10.728
10.041
1.00
23.32


ATOM
152
C
ALA
87
58.789
12.145
11.295
1.00
25.85


ATOM
153
O
ALA
87
59.114
11.536
12.300
1.00
28.57


ATOM
154
N
LEU
88
59.625
12.932
10.629
1.00
24.24


ATOM
155
CA
LEU
88
60.995
13.056
11.087
1.00
27.43


ATOM
156
CB
LEU
88
61.980
12.910
9.934
1.00
25.11


ATOM
157
CG
LEU
88
61.986
11.535
9.297
1.00
24.44


ATOM
158
CD1
LEU
88
63.143
11.477
8.366
1.00
30.54


ATOM
159
CD2
LEU
88
62.115
10.462
10.333
1.00
24.31


ATOM
160
C
LEU
88
51.326
14.315
11.872
1.00
32.71


ATOM
161
O
LEU
88
62.508
14.586
12.138
1.00
36.61


ATOM
162
N
THR
89
60.305
15.074
12.263
1.00
34.99


ATOM
163
CA
THR
89
60.530
16.303
13.017
1.00
31.40


ATOM
164
CB
THR
89
59.828
17.505
12.335
1.00
31.27


ATOM
165
OG1
THR
89
58.410
17.351
12.419
1.00
36.54


ATOM
166
CG2
THR
89
60.200
17.572
10.860
1.00
26.51


ATOM
167
C
THR
89
60.067
16.114
14.467
1.00
30.59


ATOM
168
O
THR
69
59.862
14.984
14.913
1.00
29.02


ATOM
169
N
SER
90
59.899
17.206
15.206
1.00
30.64


ATOM
170
CA
SER
90
59.474
17.091
16.605
1.00
32.41


ATOM
171
CB
SER
90
60.435
17.853
17.517
1.00
34.87


ATOM
172
OG
SER
90
60.308
19.248
17.313
1.00
42.94


ATOM
173
C
SER
90
58.024
17.513
16.871
1.00
28.38


ATOM
174
O
SER
90
57.630
17.790
18.010
1.00
25.58


ATOM
175
N
PHE
91
57.235
17.519
15.806
1.00
25.68


ATOM
176
CA
PHE
91
55.827
17.856
15.871
1.00
27.47


ATOM
177
CB
PHE
91
55.147
17.476
14.535
1.00
26.66


ATOM
178
CG
PHE
91
53.635
17.344
14.615
1.00
20.42


ATOM
179
CD1
PHE
91
52.825
18.470
14.693
1.00
21.17


ATOM
180
CD2
PHE
91
53.035
16.085
14.615
1.00
21.20


ATOM
181
CE1
PHE
91
51.454
18.351
14.766
1.00
24.02


ATOM
182
CE2
PHE
91
51.665
15.953
14.689
1.00
21.82


ATOM
183
CZ
PHE
91
50.867
17.089
14.764
1.00
23.87


ATOM
184
C
PHE
91
55.101
17.187
17.050
1.00
28.20


ATOM
185
O
PHE
91
54.310
17.841
17.735
1.00
36.57


ATOM
186
N
TYR
92
55.375
15.913
17.320
1.00
27.08


ATOM
187
CA
TYR
92
54.681
15.220
18.406
1.00
25.16


ATOM
188
CB
TYR
92
55.192
13.800
18.545
1.00
25.42


ATOM
189
CG
TYR
92
54.629
12.844
17.543
1.00
21.49


ATOM
190
CD1
TYR
92
55.357
11.734
17.146
1.00
24.41


ATOM
191
CE1
TYR
92
54.850
10.933
16.227
1.00
23.54


ATOM
192
CD2
TYR
92
53.370
13.038
16.992
1.00
24.88


ATOM
193
CE2
TYR
92
52.851
12.136
16.060
1.00
22.72


ATOM
194
CZ
TYR
92
53.598
11.034
15.688
1.00
22.21


ATOM
195
OH
TYR
92
53.085
10.100
14.810
1.00
19.19


ATOM
196
C
TYR
92
54.686
15.906
19.763
1.00
25.24


ATOM
197
O
TYR
92
53.754
15.738
20.539
1.00
22.91


ATOM
198
N
GLN
93
55.725
16.684
20.039
1.00
27.18


ATOM
199
CA
GLN
93
55.842
17.399
21.303
1.00
30.97


ATOM
200
CB
GLN
93
57.202
18.081
21.397
1.00
39.48


ATOM
201
CG
GLN
93
58.171
17.110
21.318
1.00
51.60


ATOM
202
CD
GLN
93
58.464
16.206
22.541
1.00
58.73


ATOM
203
OE1
GLN
93
58.420
14.978
22.430
1.00
63.86


ATOM
204
NE2
GLN
93
58.593
16.814
23.716
1.00
61.76


ATOM
205
C
GLN
93
54.744
18.441
21.430
1.00
31.82


ATOM
206
O
GLN
93
54.101
18.539
22.481
1.00
31.42


ATOM
207
N
SER
94
54.535
19.215
20.361
1.00
31.11


ATOM
208
CA
SER
94
53.498
20.244
20.341
1.00
29.17


ATOM
209
CB
SER
94
53.567
21.108
19.082
1.00
27.65


ATOM
210
OG
SER
94
54.701
21.944
19.083
1.00
36.29


ATOM
211
C
SER
94
52.153
19.563
20.388
1.00
30.39


ATOM
212
O
SER
94
51.294
19.937
21.104
1.00
32.51


ATOM
213
N
PHE
95
51.985
18.549
19.537
1.00
28.11


ATOM
214
CA
PHE
95
50.739
17.791
19.483
1.00
28.46


ATOM
215
CB
PHE
95
50.832
16.657
18.454
1.00
27.56


ATOM
216
CG
PHE
95
49.502
16.068
18.086
1.00
28.26


ATOM
217
CD1
PHE
95
48.473
16.883
17.610
1.00
24.62


ATOM
218
CD2
PHE
95
49.270
14.703
18.224
1.00
25.73


ATOM
219
CE1
PHE
95
47.234
16.340
17.282
1.00
22.34


ATOM
220
CE2
PHE
95
48.031
14.153
17.895
1.00
22.66


ATOM
221
CZ
PHE
95
47.011
14.971
17.424
1.00
18.98


ATOM
222
C
PHE
95
50.390
17.241
20.875
1.00
26.55


ATOM
223
O
PHE
95
49.230
17.306
21.287
1.00
29.64


ATOM
224
N
LEU
96
51.384
16.752
21.617
1.00
26.06


ATOM
225
CA
LEU
96
51.133
16.232
22.959
1.00
25.65


ATOM
226
CB
LEU
96
52.395
15.670
23.587
1.00
25.73


ATOM
227
CG
LEU
96
52.764
14.221
23.325
1.00
28.75


ATOM
228
CD1
LEU
96
53.909
13.824
24.246
1.00
31.30


ATOM
229
CD2
LEU
96
51.583
13.334
23.583
1.00
33.49


ATOM
230
C
LEU
96
50.581
17.294
23.895
1.00
25.90


ATOM
231
O
LEU
96
49.566
17.079
24.554
1.00
24.48


ATOM
232
N
ASN
97
51.240
18.444
23.951
1.00
28.33


ATOM
233
CA
ASN
97
50.785
19.512
24.840
1.00
32.74


ATOM
234
CB
ASN
97
51.680
20.753
24.742
1.00
36.47


ATOM
235
CG
ASN
97
53.154
20.434
24.807
1.00
47.89


ATOM
236
OD1
ASN
97
53.985
21.175
24.248
1.00
53.39


ATOM
237
ND2
ASN
97
53.507
19.351
25.504
1.00
52.31


ATOM
238
C
ASN
97
49.355
19.967
24.535
1.00
34.80


ATOM
239
O
ASN
97
48.555
20.198
25.444
1.00
38.94


ATOM
240
N
THR
98
49.048
20.122
23.254
1.00
31.52


ATOM
241
CA
THR
98
47.755
20.608
22.849
1.00
27.60


ATOM
242
CB
THR
98
47.855
21.264
21.458
1.00
32.02


ATOM
243
OG1
THR
98
46.576
21.759
21.047
1.00
35.15


ATOM
244
CG2
THR
98
48.389
20.301
20.449
1.00
31.67


ATOM
245
C
THR
98
46.597
19.632
22.954
1.00
26.56


ATOM
246
O
THR
98
45.568
19.985
23.504
1.00
26.90


ATOM
247
N
ILE
99
46.771
18.398
22.495
1.00
25.90


ATOM
248
CA
ILE
99
45.694
17.414
22.542
1.00
22.63


ATOM
249
CB
ILE
99
45.495
16.771
21.138
1.00
21.44


ATOM
250
CG2
ILE
99
44.567
15.567
21.204
1.00
21.56


ATOM
251
CG1
ILE
99
44.888
17.780
20.176
1.00
18.21


ATOM
252
CD1
ILE
99
43.507
18.260
20.597
1.00
21.58


ATOM
253
C
ILE
99
45.823
16.317
23.638
1.00
26.20


ATOM
254
O
ILE
99
44.823
15.947
24.283
1.00
19.95


ATOM
255
N
TRP
100
47.036
15.824
23.896
1.00
25.49


ATOM
256
CA
TRP
100
47.195
14.775
24.907
1.00
29.32


ATOM
257
CB
TRP
100
47.826
13.507
24.301
1.00
21.69


ATOM
258
CG
TRP
100
47.076
12.975
23.125
1.00
19.06


ATOM
259
CD2
TRP
100
45.988
12.031
23.134
1.00
18.83


ATOM
260
CE2
TRP
100
45.564
11.866
21.793
1.00
14.99


ATOM
261
CE3
TRP
100
45.325
11.316
24.139
1.00
18.15


ATOM
262
CD1
TRP
100
47.262
13.324
21.813
1.00
21.00


ATOM
263
NE1
TRP
100
46.357
12.667
21.013
1.00
19.19


ATOM
264
CZ2
TRP
100
44.517
11.022
21.440
1.00
14.21


ATOM
265
CZ3
TRP
100
44.278
10.471
23.777
1.00
18.67


ATOM
266
CH2
TRP
100
43.886
10.334
22.441
1.00
14.87


ATOM
267
C
TRP
100
47.945
15.199
26.176
1.00
31.48


ATOM
268
O
TRP
100
48.938
14.585
26.560
1.00
32.21


ATOM
269
N
PRO
101
47.465
16.250
26.854
1.00
34.11


ATOM
270
CD
PRO
101
46.288
17.090
26.574
1.00
34.77


ATOM
271
CA
PRO
101
48.135
16.694
28.074
1.00
38.53


ATOM
272
CB
PRO
101
47.586
18.105
28.248
1.00
38.92


ATOM
273
CG
PRO
101
46.169
17.937
27.818
1.00
37.10


ATOM
274
C
PRO
101
47.713
15.771
29.219
1.00
39.63


ATOM
275
O
PRO
101
46.600
15.224
29.192
1.00
39.50


ATOM
276
N
SER
102
48.567
15.633
30.215
1.00
41.84


ATOM
277
CA
SER
102
48.283
14.754
31.372
1.00
42.97


ATOM
278
CB
SER
102
49.412
14.819
32.397
1.00
44.81


ATOM
279
OG
SER
102
50.492
13.979
32.036
1.00
46.18


ATOM
280
C
SER
102
46.935
14.949
32.072
1.00
46.58


ATOM
281
O
SER
102
46.304
13.965
32.470
1.00
47.97


ATOM
282
N
ASP
103
46.487
16.199
32.211
1.00
47.92


ATOM
283
CA
ASP
103
45.209
16.500
32.872
1.00
48.48


ATOM
284
CB
ASP
103
45.213
17.935
33.379
1.00
51.18


ATOM
285
CG
ASP
103
45.529
18.936
32.289
1.00
54.93


ATOM
286
OD1
ASP
103
44.942
18.862
31.177
1.00
53.60


ATOM
287
OD2
ASP
103
46.375
19.813
32.558
1.00
61.10


ATOM
288
C
ASP
103
43.932
16.268
32.049
1.00
48.05


ATOM
289
O
ASP
103
42.835
16.518
32.542
1.00
52.24


ATOM
290
N
ALA
104
44.085
15.863
30.788
1.00
45.10


ATOM
291
CA
ALA
104
42.971
15.591
29.873
1.00
39.51


ATOM
292
CB
ALA
104
42.393
14.204
30.114
1.00
40.01


ATOM
293
C
ALA
104
41.863
16.630
29.850
1.00
39.09


ATOM
294
O
ALA
104
40.698
16.314
29.606
1.00
34.52


ATOM
295
N
ASP
105
42.235
17.881
30.074
1.00
38.02


ATOM
296
CA
ASP
105
41.266
18.964
30.028
1.00
39.02


ATOM
297
CB
ASP
105
41.930
20.288
30.370
1.00
43.59


ATOM
298
CG
ASP
105
42.173
20.445
31.846
1.00
52.33


ATOM
299
OD1
ASP
105
43.073
21.242
32.199
1.00
57.65


ATOM
300
OD2
ASP
105
41.465
19.781
32.650
1.00
54.73


ATOM
301
C
ASP
105
40.613
19.072
28.657
1.00
34.78


ATOM
302
O
ASP
105
39.385
19.155
28.551
1.00
35.07


ATOM
303
N
PRO
106
41.423
19.017
27.582
1.00
30.97


ATOM
304
CD
PRO
106
42.876
18.735
27.539
1.00
27.68


ATOM
305
CA
PRO
106
40.882
19.116
26.226
1.00
27.20


ATOM
306
CB
PRO
106
42.044
18.617
25.371
1.00
26.38


ATOM
307
CG
PRO
106
43.232
19.059
26.125
1.00
27.63


ATOM
308
C
PRO
106
39.639
18.259
25.990
1.00
25.44


ATOM
309
O
PRO
106
38.660
18.711
25.416
1.00
32.50


ATOM
310
N
TRP
107
39.684
17.025
26.47
1.00
22.67


ATOM
311
CA
TRP
107
38.604
16.080
26.270
1.00
21.40


ATOM
312
CB
TRP
107
39.090
14.697
26.695
1.00
21.20


ATOM
313
CG
TRP
107
40.377
14.367
26.011
1.00
21.35


ATOM
314
CD2
TRP
107
40.549
14.025
24.630
1.00
23.47


ATOM
315
CE2
TRP
107
41.926
13.818
24.418
1.00
26.19


ATOM
316
CE3
TRP
107
39.666
13.859
23.552
1.00
22.11


ATOM
317
CD1
TRP
107
41.617
14.367
26.558
1.00
22.90


ATOM
318
NE1
TRP
107
42.560
14.040
25.610
1.00
23.51


ATOM
319
CZ2
TRP
107
42.442
13.453
23.171
1.00
27.67


ATOM
320
CZ3
TRP
107
40.175
13.499
22.326
1.00
14.25


ATOM
321
CH2
TRP
107
41.551
13.294
22.144
1.00
23.37


ATOM
322
C
TRP
107
37.305
16.463
26.944
1.00
22.55


ATOM
323
O
TRP
107
36.249
16.431
26.323
1.00
17.29


ATOM
324
N
LYS
108
37.375
16.879
28.200
1.00
28.78


ATOM
325
CA
LYS
108
36.156
17.274
28.902
1.00
31.84


ATOM
326
CB
LYS
108
36.463
17.711
30.334
1.00
33.26


ATOM
327
CG
LYS
108
37.016
16.622
31.215
1.00
38.45


ATOM
328
CD
LYS
108
38.128
17.191
32.086
1.00
48.94


ATOM
329
CE
LYS
108
38.924
16.104
32.803
1.00
54.01


ATOM
330
NZ
LYS
108
40.202
16.621
33.392
1.00
55.46


ATOM
331
C
LYS
108
35.513
18.416
28.120
1.00
30.68


ATOM
332
O
LYS
108
34.296
18.572
28.130
1.00
35.50


ATOM
333
N
ALA
109
36.342
19.190
27.428
1.00
28.04


ATOM
334
CA
ALA
109
35.885
20.306
26.609
1.00
27.59


ATOM
335
CB
ALA
109
37.064
21.153
26.194
1.00
33.31


ATOM
336
C
ALA
109
35.144
19.817
25.372
1.00
26.82


ATOM
337
O
ALA
109
34.100
20.362
24.999
1.00
28.89


ATOM
338
N
PHE
110
35.588
18.796
24.723
1.00
23.59


ATOM
339
CA
PHE
110
35.043
18.245
23.548
1.00
21.61


ATOM
340
CB
PHE
110
35.998
17.325 22.801
1.00
22.67



ATOM
341
CG
PHE
110
37.166
18.041
22.180
1.00
24.76


ATOM
342
CD1
PHE
110
38.474
17.607
22.421
1.00
22.40


ATOM
343
CD2
PHE
110
36.960
19.151
21.361
1.00
19.11


ATOM
344
CE1
PHE
110
39.555
18.274
21.859
1.00
25.16


ATOM
345
CE2
PHE
110
38.033
19.818
20.796
1.00
24.29


ATOM
346
CZ
PHE
110
39.334
19.383
21.044
1.00
24.30


ATOM
347
C
PHE
110
33.791
17.482
23.965
1.00
25.43


ATOM
348
O
PHE
110
32.754
17.566
23.304
1.00
26.45


ATOM
349
N
MET
111
33.883
16.801
25.109
1.00
29.94


ATOM
350
CA
MET
111
32.788
16.020
25.687
1.00
30.42


ATOM
351
CB
MET
111
33.255
15.316
26.957
1.00
28.69


ATOM
352
CG
MET
111
34.336
14.297
26.747
1.00
32.84


ATOM
353
SD
MET
111
33.729
12.637
26.927
1.00
32.93


ATOM
354
CE
MET
111
35.263
11.745
26.874
1.00
35.32


ATOM
355
C
MET
111
31.591
16.886
26.058
1.00
31.28


ATOM
356
O
MET
111
30.478
16.375
26.195
1.00
35.76


ATOM
357
N
ALA
112
31.821
18.180
26.276
1.00
33.59


ATOM
358
CA
ALA
112
30.737
19.103
26.653
1.00
36.25


ATOM
359
CB
ALA
112
31.117
19.895
27.903
1.00
37.41


ATOM
360
C
ALA
112
30.348
20.073
25.535
1.00
35.59


ATOM
361
O
ALA
112
29.274
20.690
25.573
1.00
36.38


ATOM
362
N
GLN
113
31.192
20.153
24.517
1.00
29.50


ATOM
363
CA
GLN
111
30.958
21.070
23.433
1.00
25.32


ATOM
364
CB
GLN
113
32.137
21.034
22.459
1.00
28.47


ATOM
365
CG
GLN
113
31.821
21.592
21.09
11.00
22.47


ATOM
366
CD
GLN
113
33.006
21.581
20.152
1.00
22.91


ATOM
367
OE1
GLN
113
33.272
22.581
19.471
1.00
18.94


ATOM
368
NE2
GLN
113
33.722
20.450
20.091
1.00
16.92


ATOM
369
C
GLN
113
29.659
20.830
22.714
1.00
23.43


ATOM
370
O
GLN
113
28.956
21.770
22.387
1.00
24.46


ATOM
371
N
VAL
114
29.306
19.583
22.472
1.00
23.56


ATOM
372
CA
VAL
114
28.091
19.362
21.721
1.00
22.74


ATOM
373
CB
VAL
114
28.206
18.138
20.835
1.00
24.34


ATOM
374
CG1
VAL
114
27.267
18.280
19.657
1.00
24.59


ATOM
375
CG2
VAL
114
29.630
17.968
20.349
1.00
18.65


ATOM
376
C
VAL
114
26.818
19.322
22.563
1.00
26.29


ATOM
377
O
VAL
114
25.756
19.710
22.083
1.00
27.22


ATOM
378
N
GLU
115
26.927
18.897
23.820
1.00
26.49


ATOM
379
CA
GLU
115
25.778
18.857
24.719
1.00
23.95


ATOM
380
CB
GLU
115
26.230
18.527
26.148
1.00
26.34


ATOM
381
CG
GLU
115
26.726
17.072
26.345
1.00
27.76


ATOM
382
CD
GLU
115
27.170
16.764
27.780
1.00
34.27


ATOM
383
OE1
GLU
115
27.688
17.665
28.494
1.00
34.36


ATOM
384
OE2
GLU
115
27.005
15.604
28.200
1.00
34.20


ATOM
385
C
GLU
115
25.170
20.250
24.665
1.00
24.85


ATOM
386
O
GLU
115
23.971
20.405
24.453
1.00
26.55


ATOM
387
N
VAL
116
26.041
21.254
24.740
1.00
23.84


ATOM
388
CA
VAL
116
25.675
22.675
24.680
1.00
26.40


ATOM
389
CB
VAL
116
26.963
23.573
24.910
1.00
26.32


ATOM
390
CG1
VAL
116
26.732
25.01
724.498
1.00
22.18


ATOM
391
CG2
VAL
116
27.417
23.519
26.378
1.00
22.96


ATOM
392
C
VAL
116
24.982
23.087
23.354
1.00
31.33


ATOM
393
O
VAL
116
24.060
23.912
23.357
1.00
30.41


ATOM
394
N
LEU
117
25.428
22.516
22.233
1.00
34.23


ATOM
395
CA
LEU
117
24.884
22.852
20.912
1.00
33.73


ATOM
396
CB
LEU
117
25.917
22.601
19.801
1.00
28.04


ATOM
397
CG
LEU
117
27.208
23.430
19.781
1.00
29.91


ATOM
398
CD1
LEU
117
28.256
22.795
18.853
1.00
24.06


ATOM
399
CD2
LEU
117
26.906
24.848
19.363
1.00
25.56


ATOM
400
C
LEU
117
23.585
22.144
20.563
1.00
35.30


ATOM
401
O
LEU
117
22.852
22.593
19.692
1.00
41.08


ATOM
402
N
ILE
118
23.315
20.998
21.171
1.00
32.43


ATOM
403
CA
ILE
118
22.056
20.350
20.861
1.00
34.23


ATOM
404
CB
ILE
118
22.219
18.996
20.103
1.00
33.52


ATOM
405
CG2
ILE
118
22.754
19.223
18.688
1.00
34.50


ATOM
406
CG1
ILE
118
23.104
18.030
20.880
1.00
31.03


ATOM
407
CD1
ILE
118
23.022
16.619
20.353
1.00
28.15


ATOM
408
C
ILE
118
21.268
20.161
22.140
1.00
38.68


ATOM
409
O
ILE
118
20.284
19.420
22.174
1.00
40.44


ATOM
410
N
ASP
119
21.668
20.898
23.173
1.00
42.31


ATOM
411
CA
ASP
119
21.037
20.819
24.487
1.00
48.51


ATOM
412
CB
ASP
119
19.998
21.936
24.690
1.00
53.59


ATOM
413
CG
ASP
119
20.619
23.201
25.331
1.00
63.54


ATOM
414
OD1
ASP
119
20.738
23.251
26.582
1.00
67.03


ATOM
415
OD2
ASP
119
21.023
24.133
24.588
1.00
66.97


ATOM
416
C
ASP
119
20.515
19.416
24.824
1.00
47.46


ATOM
417
O
ASP
119
19.316
19.175
25.000
1.00
46.57


ATOM
418
N
LYS
120
21.474
18.499
24.884
1.00
45.37


ATOM
419
CA
LYS
120
21.247
17.099
25.180
1.00
43.83


ATOM
420
CB
LYS
120
21.220
16.296
23.874
1.00
48.35


ATOM
421
CG
LYS
120
20.134
15.228
23.781
1.00
54.30


ATOM
422
CD
LYS
120
20.675
14.015
23.024
1.00
64.38


ATOM
423
CE
LYS
120
19.703
12.838
22.981
1.00
66.37


ATOM
424
NZ 
LYS
120
20.427
11.562
22.663
1.00
65.78


ATOM
425
C
LYS
120
22.465
16.724
26.022
1.00
40.72


ATOM
426
O
LYS
120
23.413
17.504
26.103
1.00
36.78


ATOM
427
N
LYS
121
22.446
15.552
26.650
1.00
40.87


ATOM
428
CA
LYS
121
23.558
15.121
27.499
1.00
44.88


ATOM
429
CB
LYS
121
23.203
15.298
28.984
1.00
52.11


ATOM
430
CG
LYS
121
22.708
16.683
29.408
1.00
62.07


ATOM
431
CD
LYS
121
23.801
17.739
29.350
1.00
69.11


ATOM
432
CE
LYS
121
23.201
19.140
29.325
1.00
73.00


ATOM
433
NZ
LYS
121
24.267
20.155
29.145
1.00
75.31


ATOM
434
C
LYS
121
23.918
13.656
27.293
1.00
42.40


ATOM
435
O
LYS
121
23.043
12.839
26.977
1.00
40.70


ATOM
436
N
ILE
122
25.207
13.344
27.464
1.00
39.16


ATOM
437
CA
ILE
122
25.722
11.972
27.363
1.00
38.99


ATOM
438
CB
ILE
122
27.239
11.901
27.043
1.00
36.73


ATOM
439
CG2
ILE
122
27.612
10.470
26.694
1.00
33.95


ATOM
440
CG1
ILE
122
27.617
12.828
25.893
1.00
34.62


ATOM
441
CD1
ILE
122
29.092
13.137
25.858
1.00
27.87


ATOM
442
C
ILE
122
25.575
11.413
28.777
1.00
39.57


ATOM
443
O
ILE
122
26.043
12.018
29.743
1.00
39.64


ATOM
444
N
GLU
123
24.978
10.245
28.921
1.00
40.10


ATOM
445
CA
GLU
123
24.814
9.750
30.259
1.00
44.03


ATOM
446
CB
GLU
123
23.874
8.566
30.281
1.00
49.74


ATOM
447
CG
GLU
123
22.459
8.971
29.925
1.00
60.66


ATOM
448
CD
GLU
123
21.423
7.983
30.411
1.00
71.25


ATOM
449
OE1
GLU
123
21.199
6.953
29.724
1.00
75.21


ATOM
450
OE2
GLU
123
20.830
8.246
31.485
1.00
77.91


ATOM
451
C
GLU
123
26.138
9.462
30.922
1.00
45.02


ATOM
452
O
GLU
123
27.136
9.236
30.247
1.00
46.99


ATOM
453
N
GLU
124
26.143
9.520
32.243
1.00
45.66


ATOM
454
CA
GLU
124
27.336
9.291
33.053
1.00
46.67


ATOM
455
CB
GLU
124
26.985
9.301
34.547
1.00
58.31


ATOM
456
CG
GLU
124
26.307
8.014
35.136
1.00
79.38


ATOM
457
CD
GLU
124
24.862
7.728
34.633
1.00
86.11


ATOM
458
OE1
GLU
124
24.036
8.669
34.506
1.00
93.57


ATOM
459
OE2
GLU
124
24.545
6.535
34.414
1.00
92.35


ATOM
460
C
GLU
124
28.184
8.059
32.716
1.00
43.44


ATOM
461
O
GLU
124
29.398
8.182
32.541
1.00
41.19


ATOM
462
N
TYR
125
27.564
6.882
32.624
1.00
39.19


ATOM
463
CA
TYR
125
28.305
5.654
32.342
1.00
38.90


ATOM
464
CB
TYR
125
27.362
4.450
32.153
1.00
41.22


ATOM
465
CG
TYR
125
26.336
4.629
31.048
1.00
52.24


ATOM
466
CD1
TYR
125
26.540
4.059
29.789
1.00
57.21


ATOM
467
CE1
TYR
125
25.616
4.229
28.750
1.00
62.24


ATOM
468
CD2
TYR
125
25.169
5.373
31.251
1.00
54.99


ATOM
469
CE2
TYR
125
24.236
5.548
30.224
1.00
60.71


ATOM
470
CZ
TYR
125
24.464
4.976
28.970
1.00
65.04


ATOM
471
OH
TYR
125
23.562
5.164
27.932
1.00
65.55


ATOM
472
C
TYR
125
29.176
5.833
31.120
1.00
38.81


ATOM
473
O
TYR
125
30.398
5.774
31.198
1.00
39.40


ATOM
474
N
ALA
126
28.529
6.200
30.025
1.00
38.18


ATOM
475
CA
ALA
126
29.189
6.395
28.759
1.00
35.81


ATOM
476
CB
ALA
126
28.160
6.777
27.715
1.00
36.47


ATOM
477
C
ALA
126
30.300
7.438
28.836
1.00
35.33


ATOM
478
O
ALA
126
31.416
7.184
28.390
1.00
39.00


ATOM
479
N
LYS
127
30.015
8.575
29.457
1.00
33.83


ATOM
480
CA
LYS
127
30.979
9.666
29.580
1.00
36.03


ATOM
481
CB
LYS
127
30.264
10.897
30.143
1.00
37.06


ATOM
482
CG
LYS
127
30.934
12.227
29.859
1.00
44.50


ATOM
483
CD
LYS
127
29.936
13.399
30.033
1.00
50.75


ATOM
484
CE
LYS
127
30.562
14.783
29.762
1.00
49.31


ATOM
485
NZ
LYS
127
29.575
15.897
29.940
1.00
48.23


ATOM
486
C
LYS
127
32.235
9.330
30.412
1.00
38.28


ATOM
487
O
LYS
127
33.350
9.752
30.084
1.00
39.37


ATOM
488
N
SER
128
32.086
8.557
31.473
1.00
38.74


ATOM
489
CA
SER
128
33.262
8.242
32.281
1.00
40.98


ATOM
490
CB
SER
128
32.863
7.861
33.705
1.00
43.21


ATOM
491
OG
SER
128
31.778
6.953
33.707
1.00
54.17


ATOM
492
C
SER
128
34.102
7.155
31.621
1.00
39.36


ATOM
493
O
SER
128
35.335
7.178
31.674
1.00
38.65


ATOM
494
N
LYS
129
33.421
6.238
30.946
1.00
37.47


ATOM
495
CA
LYS
129
34.081
5.145
30.254
1.00
35.27


ATOM
496
CB
LYS
129
33.027
4.216
29.643
1.00
37.51


ATOM
497
CG
LYS
129
33.446
2.768
29.510
1.00
41.85


ATOM
498
CD
LYS
129
34.432
2.565
28.374
1.00
51.04


ATOM
499
CE
LYS
129
35.429
1.457
28.704
1.00
55.30


ATOM
500
NZ 
LYS
129
36.243
1.784
29.934
1.00
58.49


ATOM
501
C
LYS
129
34.967
5.782
29.186
1.00
33.07


ATOM
502
O
LYS
129
36.155
5.469
29.070
1.00
33.07


ATOM
503
N
ALA
130
34.415
6.740
28.460
1.00
29.50


ATOM
504
CA
ALA
130
35.192
7.414
27.438
1.00
26.51


ATOM
505
CB
ALA
130
34.335
8.429
26.699
1.00
27.54


ATOM
506
C
ALA
130
36.425
8.081
28.055
1.00
25.32


ATOM
507
O
ALA
130
37.531
7.871
27.566
1.00
29.93


ATOM
508
N
LEU
131
36.262
8.868
29.119
1.00
21.01


ATOM
509
CA
LEU
131
37.420
9.508
29.745
1.00
18.71


ATOM
510
CB
LEU
131
36.993
10.317
30.944
1.00
19.17


ATOM
511
CG
LEU
131
36.275
11.598
30.568
1.00
28.02


ATOM
512
CD1
LEU
131
35.753
12.262
31.826
1.00
32.84


ATOM
513
CD2
LEU
131
37.217
12.538
29.844
1.00
26.14


ATOM
514
C
LEU
131
38.480
8.503
30.189
1.00
21.44


ATOM
515
O
LEU
131
39.676
8.813
30.234
1.00
22.24


ATOM
516
N
ALA
132
38.030
7.311
30.557
1.00
22.62


ATOM
517
CA
ALA
132
38.917
6.236
30.997
1.00
27.46


ATOM
518
CB
ALA
132
38.089
5.090
31.584
1.00
24.97


ATOM
519
C
ALA
132
39.780
5.720
29.838
1.00
28.21


ATOM
520
O
ALA
132
41.021
5.616
29.962
1.00
28.54


ATOM
521
N
GLU
133
39.113
5.395
28.725
1.00
24.88


ATOM
522
CA
GLU
133
39.788
4.906
27.534
1.00
21.77


ATOM
523
CB
GLU
133
38.806
4.655
26.394
1.00
20.10


ATOM
524
CG
GLU
133
37.982
3.382
26.535
1.00
22.13


ATOM
525
CD
GLU
133
38.836
2.133
26.735
1.00
29.26


ATOM
526
OE1
GLU
133
39.035
1.72127.897 1.0032.94





ATOM
527
OE2
GLU
133
39.303
1.555
25.733
1.00
33.24


ATOM
528
C
GLU
133
40.798
5.938
2.7.135
1.00
22.44


ATOM
529
O
GLU
133
41.963
5.613
26.908
1.00
25.37


ATOM
530
N
LEU
134
40.367
7.198
27.137
1.00
25.68


ATOM
531
CA
LEU
134
41.237
8.330
26.794
1.00
27.08


ATOM
532
CB
LEU
134
40.439
9.650
26.759
1.00
25.70


ATOM
533
CG
LEU
134
39.500
9.925
29.573
1.00
24.82


ATOM
534
CD1
LEU
134
38.672
11.152
25.847
1.00
26.04


ATOM
535
CD2
LEU
134
40.285
10.101
24.281
1.00
23.46


ATOM
536
C
LEU
134
42.452
8.459
27.732
1.00
28.99


ATOM
537
O
LEU
134
43.526
8.874
27.296
1.00
31.43


ATOM
538
N
GLN
135
42.298
8.100
29.007
1.00
29.30


ATOM
539
CA
GLN
135
43.416
8.184
29.933
1.00
24.79


ATOM
540
CB
GLN
135
42.984
7.936
31.359
1.00
37.17


ATOM
541
CG
GLN
135
44.183
7.664
32.243
1.00
50.15


ATOM
542
CD
GLN
135
43.898
7.810
33.710
1.00
57.04


ATOM
543
OE1
GLN
135
44.561
8.593
34.395
1.00
60.77


ATOM
544
NE2
GLN
135
42.938
7.036
34.218
1.00
62.19


ATOM
545
C
GLN
135
44.445
7.154
29.565
1.00
19.79


ATOM
546
O
GLN
135
45.643
7.431
29.595
1.00
19.13


ATOM
547
N
GLY
136
43.983
5.944
29.286
1.00
18.03


ATOM
548
CA
GLY
136
44.901
4.890
28.879
1.00
21.15


ATOM
549
C
GLY
136
45.595
5.199
27.543
1.00
21.95


ATOM
550
O
GLY
136
46.760
4.862
27.338
1.00
20.39


ATOM
551
N
LEU
1.37
44.887
5.863
26.636
1.00
17.33


ATOM
552
CA
LEU
137
45.450
6.204
25.348
1.00
17.93


ATOM
553
CB
LEU
137
44.346
6.640
24.382
1.00
20.38


ATOM
554
CG
LEU
137
43.472
5.486
23.897
1.00
17.15


ATOM
555
CD1
LEU
137
42.219
5.983
23.217
1.00
22.09


ATOM
556
CD2
LEU
137
44.292
4.635
22.970
1.00
19.05


ATOM
557
C
LEU
137
46.527
7.259
25.439
1.00
18.12


ATOM
558
O
LEU
137
47.564
7.143
24.799
1.00
20.83


ATOM
559
N
GLN
138
46.294
8.293
26.231
1.00
19.01


ATOM
560
CA
GLN
138
47.274
9.364
26.373
1.00
23.17


ATOM
561
CB
GLN
138
46.756
10.428
27.354
1.00
29.42


ATOM
562
CG
GLN
138
47.680
11.615
27.608
1.00
33.61


ATOM
563
CD
GLN
138
48.671
11.359
28.736
1.00
38.81


ATOM
564
OE1
GLN
138
49.881
11.383
28.525
1.00
43.59


ATOM
565
NE2
GLN
138
48.161
11.112
29.928
1.00
40.08


ATOM
566
C
GLN
138
48.581
8.777
26.854
1.00
24.66


ATOM
567
O
GLN
138
49.654
9.111
26.359
1.00
26.00


ATOM
568
N
ASN
139
48.464
7.858
27.796
1.00
24.89


ATOM
569
CA
ASN
139
49.614
7.203
28.376
1.00
26.38


ATOM
570
CB
ASN
139
49.127
6.275
29.474
1.00
28.88


ATOM
571
CG
ASN
139
50.211
5.915
30.436
1.00
33.91


ATOM
572
OD1
ASN
139
50.747
4.798
30.407
1.00
29.67


ATOM
573
ND2
ASN
139
50.554
6.863
31.305
1.00
34.35


ATOM
574
C
ASN
139
50.432
6.422
27.328
1.00
29.07


ATOM
575
O
ASN
139
51.619
6.706
27.106
1.00
30.84


ATOM
576
N
ASN
140
49.788
5.453
26.674
1.00
27.61


ATOM
577
CA
ASN
140
50.425
4.631
25.647
1.00
26.41


ATOM
578
CB
ASN
140
49.382
3.763
24.947
1.00
28.07


ATOM
579
CG
ASN
140
49.055
2.524
25.706
1.00
26.17


ATOM
580
OD1
ASN
140
47.969
1.982
25.586
1.00
33.30


ATOM
581
ND2
ASN
140
50.001
2.042
26.431
1.00
34.68


ATOM
582
C
ASN
140
51.102
5.492
24.554
1.00
30.46


ATOM
583
O
ASN
140
52.269
5.266
24.217
1.00
31.28


ATOM
584
N
PHE
141
50.332
6.462
24.106
1.00
30.47


ATOM
585
CA
PHE
241
50.777
7.375
23.083
1.00
26.60


ATOM
586
CB
PHE
141
49.643
8.294
22.656
1.00
23.65


ATOM
587
CG
PHE
141
50.001
9.127
21.500
1.00
23.59


ATOM
588
CD1
PHE
141
50.354
8.523
20.302
1.00
19.79


ATOM
589
CD2
PHE
141
50.123
10.503
21.631
1.00
25.06


ATOM
590
OE1
PHE
141
50.840
9.269
19.254
1.00
21.84


ATOM
591
CE2
PHE
141
50.612
11.264
20.582
1.00
22.29


ATOM
592
CZ 
PHE
141
50.974
10.640
19.391
1.00
18.99


ATOM
593
C
PHE
141
51.970
8.192
23.519
1.00
26.32


ATOM
594
O
PHE
141
52.962
8.285
22.790
1.00
28.72


ATOM
595
N
GLU
142
51.900
8.774
24.710
1.00
26.35


ATOM
596
CA
GLU
142
53.025
9.568
25.197
1.00
26.18


ATOM
597
CB
GLU
142
52.657
10.297
26.484
1.00
26.40


ATOM
598
CG
GLU
142
53.828
11.060
27.085
1.00
34.98


ATOM
599
CD
GLU
142
53.429
12.038
28.189
1.00
38.85


ATOM
600
OE1
GLU
142
52.358
11.876
28.826
1.00
40.50


ATOM
601
OE2
GLU
142
54.209
12.985
28.417
1.00
41.79


ATOM
602
C
GLU
142
54.265
8.680
25.387
1.00
25.06


ATOM
603
O
GLU
142
55.394
9.097
25.125
1.00
26.60


ATOM
604
N
ASP
143
54.045
7.451
25.836
1.00
25.61


ATOM
605
CA
ASP
143
55.118
6.494
26.029
1.00
22.86


ATOM
606
CB
ASP
143
54.521
5.161
26.422
1.00
29.76


ATOM
607
CG
ASP
143
54.827
4.793
27.835
1.00
32.84


ATOM
608
OD1
ASP
143
55.385
5.646
28.546
1.00
35.88


ATOM
609
OD2
ASP
143
54.524
3.647
28.236
1.00
38.26


ATOM
610
C
ASP
143
55.820
6.341
24.704
1.00
24.52


ATOM
611
O
ASP
143
57.009
6.642
24.576
1.00
28.25


ATOM
612
N
TYR
144
55.039
5.970
23.693
1.00
22.82


ATOM
613
CA
TYR
144
55.536
5.783
22.346
1.00
17.47


ATOM
614
CB
TYR
144
54.379
5.515
21.384
1.00
18.87


ATOM
615
CG
TYR
144
54.755
5.589
19.914
1.00
20.91


ATOM
616
CD1
TYR
144
55.499
4.573
19.303
1.00
24.91


ATOM
617
CE1
TYR
144
55.859
4.653
17.944
1.00
17.76


ATOM
618
CD2
TYR
144
54.376
6.685
19.128
1.00
26.29


ATOM
619
CE2
TYR
144
54.730
6.764
17.770
1.00
19.32


ATOM
620
CZ
TYR
144
55.470
5.746
17.200
1.00
16.89


ATOM
621
OH
TYR
144
55.844
5.836
15.895
1.00
19.87


ATOM
622
C
TYR
144
55.330
6.977
21.865
1.00
17.93


ATOM
623
O
TYR
144
57.437
6.822
21.371
1.00
17.85


ATOM
624
N
VAL
145
55.776
8.173
21.987
1.00
17.19


ATOM
625
CA
VAL
145
56.507
9.328
21.509
1.00
15.32


ATOM
626
CB
VAL
145
55.734
10.599
21.731
1.00
15.48


ATOM
627
CG1
VAL
145
56.622
11.814
21.404
1.00
13.94


ATOM
628
CG2
VAL
145
54.487
10.570
20.850
1.00
9.58


ATOM
629
C
VAL
145
57.896
9.437
22.110
1.00
20.37


ATOM
630
O
VAL
145
58.856
9.754
21.405
1.00
21.53


ATOM
631
N
ASN
146
53.011
9.115
23.397
1.00
19.99


ATOM
632
CA
ASN
146
59.297
9.165
24.082
1.00
22.23


ATOM
633
CB
ASN
146
59.138
9.071
25.592
1.00
26.65


ATOM
634
CG
ASN
146
58.687
10.375
26.192
1.00
23.52


ATOM
635
OD1
ASN
146
58.612
11.393
25.506
1.00
32.61


ATOM
636
ND2
ASN
146
58.371
10.356
27.461
1.00
33.71


ATOM
637
C
ASN
146
60.239
8.117
23.584
1.00
18.20


ATOM
638
O
ASN
146
61.409
8.405
23.380
1.00
21.90


ATOM
639
N
ALA
147
59.743
6.902
23.393
1.00
17.72


ATOM
640
CA
ALA
147
60.559
5.823
22.839
1.00
17.53


ATOM
641
CB
ALA
147
59.754
4.519
22.779
1.00
17.05


ATOM
642
C
ALA
147
60.970
6.222
21.417
1.00
22.69


ATOM
643
O
ALA
147
62.035
5.828
20.933
1.00
27.83


ATOM
644
N
LEU
148
60.142
7.026
20.752
1.00
24.44


ATOM
645
CA
LEU
148
60.442
7.423
19.388
1.00
25.40


ATOM
646
CB
LEU
148
59.180
7.831
18.619
1.00
22.84


ATOM
647
CG
LEU
148
59.406
8.092
17.125
1.00
22.68


ATOM
648
CD1
LEU
148
59.589
6.805
16.326
1.00
18.18


ATOM
649
CD2
LEU
148
58.268
8.886
16.582
1.00
20.06


ATOM
650
C
LEU
148
61.480
8.508
19.308
1.00
24.34


ATOM
651
O
LEU
148
62.312
8.462
18.435
1.00
27.64


ATOM
652
N
ASN
149
61.474
9.465
20.222
1.00
28.78


ATOM
653
CA
ASN
149
62.475
10.523
20.146
1.00
31.28


ATOM
654
CB
ASN
149
62.232
11.613
21.192
1.00
43.55


ATOM
655
CG
ASN
149
60.975
12.457
20.898
1.00
55.36


ATOM
656
OD1
ASN
149
60.817
13.032
19.802
1.00
60.56


ATOM
657
ND2
ASN
149
60.085
12.545
21.883
1.00
62.05


ATOM
658
C
ASN
149
63.863
9.936
20.299
1.00
27.77


ATOM
659
O
ASN
149
64.797
10.369
19.641
1.00
25.49


ATOM
660
N
SER
150
63.965
8.917
21.145
1.00
27.48


ATOM
661
CA
SER
150
65.212
8.206
21.414
1.00
29.75


ATOM
662
CB
SER
150
64.979
7.102
22.445
1.00
32.71


ATOM
663
OG
SER
150
64.942
7.628
23.756
1.00
35.48


ATOM
664
C
SER
150
65.686
7.543
20.150
1.00
29.64


ATOM
665
O
SER
150
66.781
7.814
19.661
1.00
32.57


ATOM
665
N
TRP
151
54.841
6.652
19.645
1.00
27.07


ATOM
667
CA
TRP
151
65.092
5.909
18.428
1.00
25.09


ATOM
668
CB
TRP
151
63.611
5.254
17.953
1.00
24.27


ATOM
669
CG
TRP
151
64.046
4.513
16.726
1.00
25.31


ATOM
670
CD2
TRP
151
64.627
3.213
16.629
1.00
26.75


ATOM
671
CE2
TRP
151
64.741
2.911
15.259
1.00
26.58


ATOM
672
CE3
TRP
151
65.068
2.273
17.572
1.00
30.19


ATOM
673
CD1
TRP
151
63.828
4.940
15.455
1.00
23.89


ATOM
674
NE1
TRP
151
64.251
3.984
14.560
1.00
27.19


ATOM
675
CZ2
TRP
151
65.277
1.708
14.804
1.00
31.26


ATOM
676
CZ3
TRP
151
65.600
1.080
17.127
1.00
29.51


ATOM
677
CH2
TRP
151
65.702
0.807
15.754
1.00
32.46


ATOM
678
C
TRP
151
65.606
6.787
17.310
1.00
26.40


ATOM
679
O
TRP
151
66.545
6.421
16.590
1.00
30.03


ATOM
680
N
LYS
152
64.935
7.913
17.111
1.00
27.05


ATOM
681
CA
LYS
152
65.321
8.844
16.072
1.00
27.57


ATOM
682
CB
LYS
152
64.293
9.955
15.937
1.00
27.96


ATOM
683
CG
LYS
152
63.159
9.635
15.008
1.00
30.45


ATOM
684
CD
LYS
152
62.571
10.919
14.428
1.00
36.04


ATOM
685
CE
LYS
152
61.524
11.548
15.340
1.00
36.97


ATOM
686
N2
LYS
152
61.646
13.036
15.381
1.00
44.84


ATOM
687
C
LYS
152
66.694
9.439
16.310
1.00
28.91


ATOM
688
O
LYS
152
67.394
9.733
15.345
1.00
26.55


ATOM
689
N
LYS
153
67.041
9.670
17.580
1.00
30.64


ATOM
690
CA
LYS
153
68.340
10.245
17.974
1.00
36.17


ATOM
691
CB
LYS
153
68.280
10.789
19.406
1.00
44.14


ATOM
692
CG
LYS
153
67.324
11.951
19.642
1.00
56.90


ATOM
693
CB
LYS
153
67.670
12.702
20.941
1.00
62.05


ATOM
694
CE
LYS
153
69.026
13.431
20.818
1.00
65.84


ATOM
695
NZ
LYS
153
69.403
14.260
22.014
1.00
64.03


ATOM
696
C
LYS
153
69.533
9.282
17.935
1.00
34.62


ATOM
697
O
LYS
153
70.681
9.709
17.901
1.00
35.40


ATOM
698
N
THR
154
69.254
7.989
17.993
1.00
35.88


ATOM
699
CA
THR
154
70.279
6.950
18.024
1.00
34.95


ATOM
700
CB
THR
154
69.638
5.639
18.516
1.00
35.22


ATOM
701
OG1
THR
154
68.842
5.912
19.685
1.00
39.37


ATOM
702
CG2
THR
154
70.694
4.616
18.877
1.00
38.14


ATOM
703
C
THR
154
71.081
6.675
16.748
1.00
34.92


ATOM
704
O
THR
154
70.503
6.360
15.704
1.00
34.58


ATOM
705
N
PRO
155
72.431
6.800
16.813
1.00
35.68


ATOM
706
CD
PRO
155
73.289
7.214
17.941
1.00
32.28


ATOM
707
CA
PRO
155
73.245
6.534
15.621
1.00
34.83


ATOM
708
CB
PRO
155
74.675
6.588
16.169
1.00
31.93


ATOM
709
CG
PRO
155
74.582
7.589
17.249
1.00
30.75


ATOM
710
C
PRO
155
72.906
5.122
15.162
1.00
35.09


ATOM
711
O
PRO
155
72.585
4.266
15.983
1.00
35.97


ATOM
712
N
LEU
156
72.949
4.888
13.852
1.00
40.23


ATOM
713
CA
LEU
156
72.653
3.572
13.284
1.00
40.64


ATOM
714
CB
LEU
156
72.996
3.536
11.793
1.00
43.18


ATOM
715
CG
LEU
156
72.262
4.560
10.936
1.00
46.77


ATOM
716
CD1
LEU
156
72.581
4.315
9.462
1.00
50.39


ATOM
717
CD2
LEU
156
70.763
4.465
11.186
1.00
50.02


ATOM
718
C
LEU
156
73.488
2.546
14.004
1.00
40.37


ATOM
719
O
LEU
156
72.967
1.569
14.514
1.00
43.12


ATOM
720
N
SER
157
74.782
2.832
14.097
1.00
41.57


ATOM
721
CA
SER
151
75.768
1.982
14.772
1.00
39.37


ATOM
722
CB
SER
157
77.108
2.720
14.810
1.00
42.46


ATOM
723
OG
SER
257
76.917
4.128
14.988
1.00
48.99


ATOM
724
C
SER
157
75.380
1.580
16.195
1.00
36.91


ATOM
725
O
SER
157
75.728
0.495
16.662
1.00
34.45


ATOM
726
N
LEU
158
74.646
2.443
16.881
1.00
34.52


ATOM
727
CA
LEU
158
74.264
2.133
18.242
1.00
35.24


ATOM
728
CB
LEU
158
74.391
3.371
19.121
1.00
33.75


ATOM
729
CG
LEU
158
75.760
4.029
19.172
1.00
28.13


ATOM
730
CD1
LEU
158
75.699
5.261
20.058
1.00
28.41


ATOM
731
CD2
LEU
158
76.758
3.025
19.703
1.00
28.88


ATOM
732
C
LEU
158
72.877
1.535
18.402
1.00
36.64


ATOM
733
O
LEU
158
72.450
1.284
19.530
1.00
43.40


ATOM
734
N
ARG
159
72.156
1.315
17.309
1.00
34.12


ATOM
735
CA
ARG
159
70.816
0.726
17.416
1.00
34.54


ATOM
736
CB
ARG
159
70.002
1.061
16.178
1.00
35.15


ATOM
737
CG
ARG
159
69.756
2.533
16.051
1.00
36.06


ATOM
738
CD
ARG
159
69.290
2.938
14.676
1.00
35.14


ATOM
739
NE
ARG
159
68.887
4.331
14.741
1.00
38.24


ATOM
740
CZ 
ARG
159
68.047
4.902
13.899
1.00
42.17


ATOM
741
NH1
ARG
159
67.731
6.181
14.043
1.00
44.23


ATOM
742
NH2
ARG
159
67.537
4.191
12.906
1.00
45.95


ATOM
743
C
ARG
159
70.886
−0.790
17.653
1.00
32.88


ATOM
744
O
ARG
159
71.503
−1.518
16.877
1.00
36.83


ATOM
745
N
SER
160
70.249
−1.253
18.723
1.00
27.95


ATOM
746
CA
SER
160
70.280
−2.659
19.105
1.00
24.33


ATOM
747
CB
SER
160
70.578
−2.744
20.595
1.00
26.10


ATOM
748
OG
SER
160
69.572
−2.088
21.356
1.00
24.55


ATOM
749
C
SER
160
68.982
−3.386
18.856
1.00
26.96


ATOM
750
O
SER
160
67.957
−2.749
18.632
1.00
31.18


ATOM
751
N
LYS
161
68.997
−4.713
18.980
1.00
27.03


ATOM
752
CA
LYS
161
67.781
−5.503
18.793
1.00
27.02


ATOM
753
CB
LYS
161
68.109
−6.990
18.781
1.00
28.66


ATOM
754
CG
LYS
161
69.045
−7.392
17.649
1.00
40.43


ATOM
755
CD
LYS
161
68.316
−7.505
16.298
1.00
49.88


ATOM
756
CE
LYS
161
69.283
−7.711
15.104
1.00
52.99


ATOM
757
NZ
LYS
161
68.622
−8.340
13.896
1.00
55.88


ATOM
758
C
LYS
161
66.810
−5.196
19.934
1.00
26.74


ATOM
759
O
LYS
161
65.596
−5.320
19.789
1.00
25.11


ATOM
760
N
ARG
162
67.369
−4.805
21.073
1.00
25.21


ATOM
761
CA
ARG
162
66.591
−4.459
22.257
1.00
25.16


ATOM
762
CB
ARG
162
67.536
−4.141
23.420
1.00
27.16


ATOM
763
CG
ARG
162
66.939
−4.222
24.815
1.00
27.89


ATOM
764
CD
ARG
162
67.605
−3.206
25.743
1.00
29.60


ATOM
765
NE
ARG
162
67.109
−1.850
25.492
1.00
28.75


ATOM
766
CZ
ARG
162
67.830
−0.859
24.963
1.00
30.83


ATOM
767
NH1
ARG
162
69.101
−1.050
24.615
1.00
35.66


ATOM
768
NH2
ARG
162
67.279
0.329
24.765
1.00
21.65


ATOM
769
C
ARG
162
65.766
−3.218
21.903
1.00
25.08


ATOM
770
O
ARG
162
64.568
−3.169
22.173
1.00
22.87


ATOM
771
N
SER
163
66.421
−2.236
21.293
1.00
25.20


ATOM
772
CA
SER
163
65.768
−0.997
20.890
1.00
27.25


ATOM
773
CB
SER
163
66.762
−0.043
20.233
1.00
28.12


ATOM
774
OG
SER
163
67.671
0.494
21.170
1.00
33.02


ATOM
775
C
SER
163
64.648
−1.279
19.911
1.00
30.21


ATOM
776
O
SER
163
63.576
−0.691
20.009
1.00
35.47


ATOM
777
N
GLN
164
64.913
−2.159
18.946
1.00
30.80


ATOM
778
CA
GLN
164
63.919
−2.520
17.938
1.00
29.81


ATOM
779
CB
GLN
164
64.499
−3.481
16.903
1.00
31.88


ATOM
780
CG
GLN
164
65.539
−2.859
15.992
1.00
35.34


ATOM
781
CD
GLN
164
65.955
−3.784
14.866
1.00
35.38


ATOM
782
OE1
GLN
164
66.055
−4.994
15.049
1.00
36.50


ATOM
783
NE2
GLN
164
66.155
−3.219
13.690
1.00
37.36


ATOM
784
C
GLN
164
62.723
−3.176
18.588
1.00
27.06


ATOM
765
O
GLN
164
61.599
−2.696
18.465
1.00
28.49


ATOM
786
N
ASP
165
62.984
−4.290
19.260
1.00
27.83


ATOM
787
CA
ASP
165
61.962
−5.043
19.956
1.00
28.49


ATOM
788
CB
ASP
165
62.588
−6.148
20.822
1.00
33.50


ATOM
789
CG
ASP
165
63.140
−7.321
20.004
1.00
38.35


ATOM
790
OD1
ASP
165
62.828
−7.442
18.802
1.00
43.20


ATOM
791
OD2
ASP
165
63.886
−8.152
20.573
1.00
41.66


ATOM
792
C
ASP
165
61.123
−4.118
20.820
1.00
28.33


ATOM
793
O
ASP
165
59.900
−4.146
20.719
1.00
29.40


ATOM
794
N
ARG
166
61.748
−3.267
21.635
1.00
26.02


ATOM
795
CA
ARG
166
60.928
−2.404
22.453
1.00
30.80


ATOM
796
CB
ARG
166
61.638
−1.826
23.703
1.00
41.63


ATOM
797
CG
ARG
166
62.815
−0.854
23.491
1.00
63.41


ATOM
798
CD
ARG
166
62.451
0.565
22.887
1.00
74.62


ATOM
799
NE
ARG
166
63.602
1.218
22.219
1.00
79.94


ATOM
800
CZ
ARG
166
63.505
2.185
21.299
1.00
80.41


ATOM
801
NH1
ARG
166
64.607
2.721
20.751
1.00
81.58


ATOM
802
NH2
ARG
166
62.308
2.607
20.911
1.00
81.81


ATOM
803
C
ARG
166
60.132
−1.356
21.699
1.00
29.00


ATOM
804
O
ARG
166
58.930
−1.280
21.909
1.00
29.60


ATOM
805
N
ILE
167
60.738
−0.608
20.777
1.00
26.06


ATOM
806
CA
ILE
167
59.963
0.394
20.066
1.00
23.75


ATOM
807
CB
ILE
167
60.810
1.191
19.093
1.00
20.38


ATOM
808
CG2
ILE
167
61.452
0.280
18.112
1.00
25.06


ATOM
809
CG1
ILE
167
59.951
2.228
18.385
1.00
20.43


ATOM 
810
CD1
ILE
167
60.140
3.600
18.837
1.00
18.35


ATOM
811
C
ILE
167
58.753
−0.240
19.363
1.00
28.10


AI'OM
812
O
ILE
167
57.628
0.240
19.495
1.00
29.42


ATOM
813
N
ARG
168
58.945
−1.384
18.698
1.00
28.88


ATOM
814
CA
ARG
168
57.817
2.048
18.033
1.00
32.17


ATOM
815
CB
ARG
168
58.232
−3.386
17.437
1.00
31.63


ATOM
816
CG
ARG
168
58.640
−3.323
16.009
1.00
37.29


ATOM
817
CD
ARG
168
58.832
−4.719
15.462
1.00
37.37


ATOM
818
NE
ARG
168
60.200
−5.185
15.647
1.00
34.57


ATOM
819
CZ
ARG
168
60.529
−6.378
16.122
1.00
33.36


ATOM
820
NH1
ARG
168
61.810
−6.699
16.249
1.00
34.45


ATOM
821
NE2
ARG
168
59.584
−7.235
16.487
1.00
35.04


ATOM
822
C
ARG
168
56.674
−2.321
19.000
1.00
34.64


ATOM
823
O
ARG
168
55.541
−1.914
18.769
1.00
39.25


ATOM
824
N
GLU
169
56.998
−3.021
20.079
1.00
37.29


ATOM
825
CA
GLU
169
56.059
−3.410
21.129
1.00
39.87


ATOM
826
CB
GLU
169
56.860
−3.956
22.320
1.00
48.72


ATOM
827
CG
GLU
169
56.049
−4.600
23.449
1.00
55.06


ATOM
828
CD
GLU
159
56.945
−5.101
24.578
1.00
57.67


ATOM
829
OE1
GLU
169
57.900
−4.379
24.949
1.00
55.59


ATOM
830
OE2
GLU
169
56.692
−6.214
25.091
1.00
58.16


ATOM
831
C
GLU
169
55.181
−2.250
21.580
1.00
38.09


ATOM
832
O
GLU
169
54.004
−2.425
21.898
1.00
33.57


ATOM
833
N
LEU
170
55.781
−1.069
21.615
1.00
32.71


ATOM
834
CA
LEU
170
55.093
0.135
22.005
1.00
29.32


ATOM
835
CB
LEU
170
56.097
1.231
22.321
1.00
27.42


ATOM
836
CG
LEU
170
56.464
1.321
23.795
1.00
29.26


ATOM
837
CD1
LEU
170
57.580
2.378
24.032
1.00
20.06


ATOM
838 
CD2
LEU
170
55.165
1.641
24.552
1.00
25.26


ATOM
839
C
LEU
170
54.197
0.595
20.893
1.00
28.58


ATOM
840
O
LEU
170
53.050
0.943
21.135
1.00
37.18


ATOM
841
N
PHE
171
54.709
0.611
19.671
1.00
24.66


ATOM
842
CA
PHE
171
53.899
1.063
16.563
1.00
22.29


ATOM
843
CB
PHE
171
54.699
1.053
17.247
1.00
19.78


ATOM
844
CG
PHE
171
53.874
1.411
16.018
1.00
17.53


ATOM
845
CD1
PHE
171
53.766
2.731
15.590
1.00
11.80


ATOM
846
CD2
PHE
171
53.148
0.422
15.330
1.00
14.77


ATOM
847
CE1
PHE
171
52.941
3.067
14.504
1.00
11.46


ATOM
848
CE2
PHE
171
52.315
0.758
14.242
1.00
10.44


ATOM
849
CZ
PHE
171
52.214
2.085
13.836
1.00
6.72


ATOM
850
C
PHE 
171
52.659
0.183
18.471
1.00
21.88


ATOM
851
O
PHE 
171
51.556
0.693
18.381
1.00
23.54


ATOM
852
N
SER
172
52.839
−1.129
18.540
1.00
23.14


ATOM
853
CA
SER
172
51.729
−2.069
18.428
1.00
27.99


ATOM
854
CB
SER
172
52.228
−3.504
18.485
1.00
27.59


ATOM
855
C
SER
172
53.331
−3.669
17.624
1.00
31.04


ATOM
856
C
SER
172
50.751
−1.875
19.547
1.00
33.07


ATOM
857
O
SER
172
49.564
−2.166
19.392
1.00
38.22


ATOM
858
N
GLN
173
51.276
−1.425
20.684
1.00
36.24


ATOM
859
CA
GLN
173
50.509
−1.166
21.903
1.00
37.57


ATOM
860
CB
GLN
173
51.499
−0.888
23.068
1.00
44.34


ATOM
861
CG
GLN
173
50.894
−0.718
24.476
1.00
54.23


ATOM
862
CD
GLN
173
51.291
−1.831
25.447
1.00
60.34


ATOM
863
OE1
GLN
173
51.402
−1.609
26.559
1.00
57.52


ATOM
864
NE2
GLN
173
51.482
−3.040
24.921
1.00
66.46


ATOM
865
C
GLN
173
49.557
0.031
21.692
1.00
32.96


ATOM
866
O
GLN
173
48.324
−0.078
21.833
1.00
30.70


ATOM
867
N
ALA
174
50.142
1.166
21.342
1.00
25.13


ATOM
868
CA
ALA
174
49.371
2.356
21.124
1.00
23.49


ATOM
869
CB
ALA
174
50.208
3.499
20.814
1.00
20.35


ATOM
870
C
ALA
174
48.368
2.139
20.008
1.00
22.23


ATOM
871
O
ALA
174
47.176
2.342
20.208
1.00
28.71


ATOM
872
N
GLU
175
48.833
1.646
18.865
1.00
23.39


ATOM
873
CA
GLU
175
47.973
1.415
17.703
1.00
24.62


ATOM
874
CB
GLU
175
48.790
0.901
16.505
1.00
23.76


ATOM
875
CG
GLU
175
48.055
0.935
15.154
1.00
28.00


ATOM
876
CD
GLU
175
47.069
−0.208
14.953
1.00
24.81


ATOM
877
OE1
GLU
175
47.415
−1.356
15.249
1.00
30.25


ATOM
878
OE2
GLU
175
45.944
0.031
14.493
1.00
25.54


ATOM
879
C
GLU
175
46.815
0.465
17.975
1.00
23.05


ATOM
880
O
GLU
175
45.680
0.718
17.549
1.00
23.75


ATOM
881
N
SER
176
47.117
−0.658
18.610
1.00
23.70


ATOM
882
CA
SER
176
46.093
−1.633
18.939
1.00
25.29


ATOM
883
CB
SER
176
46.720
−2.904
19.483
1.00
27.82


ATOM
884
OG
SER
176
45.715
−3.746
20.007
1.00
37.64


ATOM
885
C
SER
176
45.113
−1.066
19.955
1.00
27.15


ATOM
886
O
SER
176
43.911
−1.266
19.827
1.00
29.62


ATOM
887
N
HIS
177
45.616
−0.343
20.953
1.00
27.84


ATOM
888
CA
HIS
177
44.736
0.231
21.947
1.00
29.40


ATOM
889
CB
HIS
177
45.525
0.880
23.083
1.00
35.05


ATOM
890
CG
HIS
177
44.670
1.358
24.221
1.00
39.71


ATOM
891
CD2
HIS
177
43.330
1.519
24.331
1.00
39.99


ATOM
892
ND1
HIS
177
45.195
1.730
25.442
1.00
45.29


ATOM
893
CE1
HIS
177
44.215
2.098
26.251
1.00
43.30


ATOM
894
NE2
HIS
177
43.072
1.979
25.598
1.00
41.68


ATOM
895
C
HIS
177
43.827
1.248
21.262
1.00
31.02


ATOM
896
O
HIS
177
42.624
1.300
21.534
1.00
35.22


ATOM
897
N
PHE
178
44.369
2.050
20.359
1.00
28.97


ATOM
898
CA
PHE
178
43.525
3.023
19.683
1.00
28.86


ATOM
899
CG
PHE
178
44.358
3.929
18.779
1.00
25.66


ATOM
900
CG
PHE
178
44.816
5.209
19.441
1.00
22.69


ATOM
901
CD1
PHE
178
46.085
5.312
19.993
1.00
25.93


ATOM
902
CD2
PHE
178
44.019
6.347
19.411
1.00
23.46


ATOM
903
CE1
PHE
178
46.560
6.537
20.490
1.00
20.31


ATOM
904
CE2
PHE
170
44.485
7.567
19.906
1.00
21.41


ATOM
905
CZ
PHE
178
45.757
7.654
20.439
1.00
21.04


ATOM
906
C
PHE
178
42.457
2.290
18.875
1.00
29.52


ATOM
907
O
PHE
178
41.268
2.545
19.022
1.00
25.37


ATOM
908
N
ARG
179
42.888
1.299
18.105
1.00
32.49


ATOM
909
CA
ARG
179
41.989
0.525
17.269
1.00
30.66


ATOM
910
CB
ARG
179
42.733
−0.654
16.646
1.00
31.64


ATOM
911
CG
ARG
179
41.976
−1.291
15.519
1.00
34.21


ATOM
912
CD
ARG
179
42.831
−2.263
14.759
1.00
41.71


ATOM
913
NE
ARG
179
42.897
−3.560
15.417
1.00
45.91


ATOM
914
CZ
ARG
179
44.010
−4.095
15.909
1.00
52.23


ATOM
915
NH1
ARG
179
45.166
−3.448
15.815
1.00
48.56


ATOM
916
NH2
ARG
179
43.961
−5.278
16.518
1.00
60.56


ATOM
917
C
ARG
179
40.780
0.018
18.026
1.00
29.30


ATOM
918
O
ARG
179
39.656
0.169
17.574
1.00
34.87


ATOM
919
N
ASN
180
41.004
−0.537
19.201
1.00
29.94


ATOM
920
CA
ASN
180
39.911
−1.077
19.992
1.00
32.10


ATOM
921
CB
ASN
180
40.418
−2.277
20.804
1.00
36.87


ATOM
922
CG
ASN
180
41.000
−3.393
19.917
1.00
38.96


ATOM
923
OD1
ASN
180
40.358
−3.861
18.981
1.00
40.44


ATOM
924
ND2
ASN
180
42.214
−3.821
20.224
1.00
42.74


ATOM
925
C
ASN
180
39.125
−0.073
20.875
1.00
32.03


ATOM
926
O
ASN
180
38.036
−0.387
21.337
1.00
34.18


ATOM
927
N
SER
181
39.661
1.126
21.105
1.00
32.59


ATOM
928
CA
SER
181
38.965
2.150
21.904
1.00
26.92


ATOM
929
CB
SER
181
39.939
3.211
22.429
1.00
27.48


ATOM
930
OG
SER
181
40.884
2.658
23.324
1.00
31.01


ATOM
931
C
SER
181
37.883
2.902
21.134
1.00
25.45


ATOM
932
O
SER
181
36.871
3.288
21.705
1.00
25.81


ATOM
933
N
MET
182
38.111
3.143
19.847
1.00
23.99


ATOM
934
CA
MET
182
37.169
3.898
19.014
1.00
24.66


ATOM
935
CB
MET
182
37.418
3.676
17.519
1.00
25.35


ATOM
936
CG
MET
182
38.588
4.436
16.936
1.00
22.11


ATOM
937
SD
MET
182
38.582
6.169
17.397
1.00
31.27


ATOM
938
CE
MET
182
40.288
6.254
17.748
1.00
28.00


ATOM
939
C
MET
182
35.697
3.699
19.298
1.00
22.86


ATOM
940
O
MET
182
34.946
4.674
19.354
1.00
26.55


ATOM
941
N
PRO
183
35.257
2.448
19.504
1.00
20.02


ATOM
942
CD
PRO
183
35.911
1.131
19.367
1.00
17.72


ATOM
943
CA
PRO
183
33.814
2.311
19.771
1.00
20.18


ATOM
944
CB
PRO
183
33.626
0.790
19.918
1.00
19.03


ATOM
945
CG
PRO
183
34.758
0.210
19.057
1.00
15.96


ATOM
946
C
PRO
183
33.306
3.109
20.990
1.00
21.68


ATOM
947
O
PRO
183
32.167
3.557
20.995
1.00
27.17


ATOM
948
N
SER
184
34.166
3.342
21.986
1.00
22.98


ATOM
949
CA
SER
184
33.813
4.107
23.186
1.00
18.39


ATOM
950
CB
SER
184
34.968
4.066
24.198
1.00
15.92


ATOM
951
OG
SER
184
35.328
2.729
24.522
1.00
15.22


ATOM
952
C
SER
184
33.432
5.568
22.895
1.00
21.41


ATOM
953
O
SER
184
32.924
6.254
23.776
1.00
17.59


ATOM
954
N
PHE
185
33.702
6.057
21.682
1.00
20.87


ATOM
955
CA
PHE
185
33.367
7.435
21.342
1.00
21.72


ATOM
956
CB
PHE
185
34.591
8.195
20.843
1.00
19.91


ATOM
957
CG
PHE
185
35.865
7.657
21.578
1.00
23.10


ATOM
958
CD1
PHE
185
37.033
7.561
20.875
1.00
20.78


ATOM
959
CD2
PHE
185
35.909
7.840
22.960
1.00
19.79


ATOM
960
CE1
PHE
185
38.226
7.252
21.546
1.00
23.07


ATOM
961
CE2
PHE
185
37.106
7.529
23.633
1.00
25.58


ATOM
962
CZ
PHE
185
38.262
7.235
22.920
1.00
16.31


ATOM
963
C
PHE
185
32.306
7.429
20.261
1.00
24.33


ATOM
964
O
PHE
185
32.075
8.432
19.599
1.00
24.66


ATOM
965
N
ALA
186
31.613
6.306
20.134
1.00
28.12


ATOM
966
CA
ALA
186
30.581
6.146
19.116
1.00
27.05


ATOM
967
CB
ALA
186
31.189
5.473
17.870
1.00
29.72


ATOM
968
C
ALA
186
29.469
5.283
19.684
1.00
26.76


ATOM
969
O
ALA
186
28.840
4.492
18.969
1.00
26.03


ATOM
970
N
VAL
187
29.265
5.415
20.986
1.00
27.16


ATOM
971
CA
VAL
187
28.238
4.661
21.689
1.00
29.69


ATOM
972
CB
VAL
187
28.175
5.047
23.170
1.00
29.53


ATOM
973
CG1
VAL
187
27.451
3.966
23.923
1.00
32.69


ATOM
974
CG2
VAL 
187
29.555
5.282
23.730
1.00
31.55


ATOM
975
C
VAL
187
26.867
4.963
21.042
1.00
30.99


ATOM
976
O
VAL
187
26.544
6.121
20.818
1.00
32.51


ATOM
977
N
SER
168
26.045
3.933
20.944
1.00
33.95


ATOM
978
CA
SER
188
24.703
4.094
20.352
1.00
39.13


ATOM
979
CB
SER
188
23.924
2.782
20.524
1.00
37.12


ATOM
980
OG
SER
188
23.056
2.573
19.415
1.00
42.00


ATOM
981
C
SER
188
23.960
5.228
21.104
1.00
40.12


ATOM
982
O
SER
188
24.106
5.401
22.316
1.00
42.73


ATOM
983
N
LYS
189
23.231
6.038
20.338
1.00
42.58


ATOM
984
CA
LYS
189
22.468
7.158
20.883
1.00
43.93


ATOM
985
CB
LYS
189
21.718
6.715
22.151
1.00
51.42


ATOM
986
CG
LYS
189
20.770
7.737
22.743
1.00
65.46


ATOM
987
CD
LYS
189
20.195
7.249
24.074
1.00
75.80


ATOM
988
CE
LYS
189
19.366
8.343
24.769
1.00
83.02


ATOM
989
NZ 
LYS
189
18.929
7.964
26.159
1.00
86.33


ATOM
990
C
LYS
189
23.322
8.395
21.177
1.00
39.73


ATOM
991
O
LYS
169
22.799
9.507
21.251
1.00
40.92


ATOM
992
N
PHE
190
24.633
8.220
21.297
1.00
36.45


ATOM
993
CA
PHE
190
25.532
9.339
21.596
1.00
32.97


ATOM
994
CB
PHE
190
26.266
9.053
22.906
1.00
35.66


ATOM
995
CG
PHE
190
25.349
8.799
24.059
1.00
37.16


ATOM
996
CD1
PHE
190
25.189
7.510
24.544
1.00
37.15


ATOM
997
CD2
PHE
190
24.620
9.841
24.623
1.00
37.31


ATOM
998
CE1
PHE
190
24.279
7.259
25.568
1.00
36.95


ATOM
999
CE2
PHE
190
23.722
9.602
25.652
1.00
37.94


ATOM
1000
CZ
PHE
190
23.551
8.310
26.124
1.00
37.75


ATOM
1001
C
PHE
190
26.554
9.640
20.499
1.00
28.22


ATOM
1002
O
PHE 
190
27.573
10.285
20.746
1.00
27.75


ATOM
1003
N
GLU
191
26.270
9.210
19.280
1.00
27.87


ATOM
1004
CA
GLU
191
27.212
9.420
18.196
1.00
25.18


ATOM
1005
CB
GLU
191
26.823
8.642
16.961
1.00
23.69


ATOM
1006
CG
GLU
191
26.809
7.147
17.187
1.00
25.09


ATOM
1007
CD
GLU
191
25.416
6.613
17.376
1.00
26.96


ATOM
1008
OE1
GLU
191
25.157
5.496
16.884
1.00
31.29


ATOM
1009
OE2
GLU
191
24.575
7.304
18.000
1.00
27.39


ATOM
1010
C
GLU
191
27.439
10.865
17.869
1.00
25.02


ATOM
1011
O
GLU
191
28.576
11.247
17.631
1.00
27.85


ATOM
1012
N
VAL
192
26.391
11.685
17.898
1.00
27.84


ATOM
1013
CA
VAL
192
26.557
13.114
17.620
1.00
25.95


ATOM
1014
CB
VAL
192
25.232
13.804
17.352
1.00
26.44


ATOM
1015
CG1
VAL
192
25.468
15.283
17.037
1.00
24.26


ATOM
1016
CG2
VAL
192
24.489
13.089
16.240
1.00
22.90


ATOM
1017
C
VAL
192
27.245
13.824
18.793
1.00
28.20


ATOM
1018
O
VAL
192
28.198
14.584
18.605
1.00
33.10


ATOM
1019
N
LEU
193
26.805
13.541
20.010
1.00
24.52


ATOM
1020
CA
LEU
193
27.408
14.174
21.178
1.00
25.78


ATOM
1021
CB
LEU
193
26.669
13.706
22.436
1.00
25.22


ATOM
1022
CG
LEU
193
25.241
14.207
22.612
1.00
17.24


ATOM
1023
CD1
LEU
193
24.489
13.345
23.599
1.00
24.15


ATOM
1024
CD2
LEU
193
25.303
15.634
23.111
1.00
22.79


ATOM
1025
C
LEU
193
28.936
13.937
21.316
1.00
27.53


ATOM
1026
O
LEU
193
29.675
14.798
21.835
1.00
22.52


ATOM
1027
N
PHE
194
29.394
12.767
20.860
1.00
28.95


ATOM
1028
CA
PHE
194
30.809
12.371
20.912
1.00
27.24


ATOM
1029
CB
PHE
194
30.926
10.838
21.023
1.00
23.99


ATOM
1030
CG
PHE
194
30.883
10.302
22.424
1.00
19.23


ATOM
1031
CD1
PHE
194
29.946
9.331
22.771
1.00
16.74


ATOM
1032
CD2
PHE
194
31.806
10.734
23.381
1.00
12.01


ATOM
1033
CE1
PHE
194
29.924
8.790
24.058
1.00
20.23


ATOM
1034
CE2
PHE
194
31.807
10.213
24.670
1.00
15.47


ATOM
1035
CZ
PHE
194
30.862
9.233
25.019
1.00
21.85


ATOM
1036
C
PHE
194
31.597
12.769
19.653
1.00
30.35


ATOM
1037
O
PHE
194
32.771
12.413
19.540
1.00
33.71


ATOM
1038
N
LEU
195
30.990
13.512
18.730
1.00
27.41


ATOM
1039
CA
LEU
195
31.659
13.845
17.466
1.00
23.44


ATOM
1040
CB
LEU
195
30.755
14.704
16.592
1.00
24.37


ATOM
1041
CG
LEU
195
30.899
14.393
15.109
1.00
30.12


ATOM
1042
CD1
LEU
195
30.651
12.891
14.842
1.00
26.11


ATOM
1043
CD2
LEU
195
29.922
15.244
14.338
1.00
30.52


ATOM
1044
C
LEU
195
33.074
14.407
17.465
1.00
18.68


ATOM
1045
O
LEU
195
33.954
13.869
16.809
1.00
20.43


ATOM
1046
N
PRO
196
33.316
15.503
18.173
1.00
16.00


ATOM
1047
CD
PRO
196
32.351
16.380
18.850
1.00
13.80


ATOM
1048
CA
PRO
196
34.668
16.072
18.193
1.00
14.01


ATOM
1049
CB
PRO
196
34.491
17.343
18.991
1.00
14.53


ATOM
1050
CG
PRO
196
33.026
17.698
18.756
1.00
16.77


ATOM
1051
C
PRO
196
35.683
15.150
18.848
1.00
17.13


ATOM
1052
O
PRO
196
36.828
15.048
18.395
1.00
19.94


ATOM
1053
N
THR
197
35.268
14.499
19.929
1.00
18.61


ATOM
1054
CA
THR
197
36.118
13.557
20.659
1.00
20.79


ATOM
1055
CP
THR
197
35.320
12.890
21.797
1.00
24.29


ATOM
1056
OG1
THR
197
34.828
13.892
22.688
1.00
26.50


ATOM
1057
CG2
THR
197
36.182
11.905
22.554
1.00
20.17


ATOM
1058
C
THR
197
36.588
12.453
19.699
1.00
23.61


ATOM
1059
O
THR
197
37.780
12.111
19.663
1.00
26.22


ATOM
1060
N
TYR
198
35.631
11.891
18.946
1.00
21.68


ATOM
1061
CA
TYR
198
35.870
10.837
17.953
1.00
15.60


ATOM
1062
CB
TYR
198
34.545
10.373
17.342
1.00
12.95


ATOM
1063
CG
TYR
198
34.661
9.276
16.294
1.00
18.00


ATOM
1064
CD1
TYR
198
34.391
7.946
16.613
1.00
14.34


ATOM
1065
CE1
TYR
198
34.482
6.948
15.659
1.00
21.67


ATOM
1066
CD2
TYR
198
35.029
9.569
14.975
1.00
20.14


ATOM
1067
CE2
TYR
198
35.121
8.564
14.010
1.00
20.73


ATOM
1068
CZ
TYR
198
34.848
7.268
14.360
1.00
18.41


ATOM
1069
OH
TYR
198
34.917
6.287
13.407
1.00
24.92


ATOM
1070
C
TYR
198
36.807
11.342
16.850
1.00
19.32


ATOM
1071
O
TYR
198
37.813
10.700
16.554
1.00
19.54


ATOM
1072
N
ALA
199
36.494
12.487
16.251
1.00
14.36


ATOM
1073
CA
ALA
199
37.342
13.020
15.205
1.00
14.32


ATOM
1074
CB
ALA
199
36.818
14.357
14.748
1.00
16.43


ATOM
1075
C
ALA
199
38.789
13.146
15.694
1.00
16.89


ATOM
1076
O
ALA
199
39.714
12.639
15.044
1.00
16.56


ATOM
1077
N
GLN
200
38.964
13.765
16.868
1.00
18.58


ATOM
1078
CA
GLN
200
40.281
13.984
17.492
1.00
18.04


ATOM
1079
CB
GLN
200
40.151
14.844
18.744
1.00
16.98


ATOM
1080
CG
GLN
200
39.629
16.239
18.489
1.00
16.64


ATOM
1081
CD
GLN
200
40.593
17.109
17.709
1.00
17.76


ATOM
1082
OE1
GLN
200
41.811
16.965
17.821
1.00
20.73


ATOM
1083
NE2
GLN
200
40.051
18.032
16.926
1.00
16.40


ATOM
1084
C
GLN
200
41.067
12.721
17.833
1.00
16.13


ATOM
1085
O
GLN
200
42.287
12.732
17.758
1.00
18.50


ATOM
1086
N
ALA
201
40.393
11.665
18.276
1.00
15.14


ATOM
1087
CA
ALA
201
41.093
10.414
18.578
1.00
15.80


ATOM
1088
CB
ALA
201
40.244
9.507
19.463
1.00
11.71


ATOM
1089
C
ALA
201
41.447
9.696
17.277
1.00
15.73


ATOM
1090
O
ALA
201
42.521
9.110
17.155
1.00
23.19


ATOM
1091
N
ALA
202
40.528
9.724
15.315
1.00
16.63


ATOM
1092
CA
ALA
202
40.714
9.105
15.007
1.00
10.64


ATOM
1093
CB
ALA
202
39.519
9.386
14.120
1.00
12.27


ATOM
1094
C
ALA
202
41.954
9.686
14.376
1.00
11.25


ATOM
1095
O
ALA
202
42.855
8.966
13.963
1.00
12.02


ATOM
1096
N
ASN
203
42.005
11.005
14.328
1.00
10.25


ATOM
1097
CA
ASN
203
43.143
11.684
13.767
1.00
14.32


ATOM
1098
CB
ASN
203
43.015
13.167
14.008
1.00
14.52


ATOM
1099
CG
ASN
203
44.207
13.926
13.501
1.00
15.52


ATOM
1100
OD1
ASN
203
44.459
13.939
12.310
1.00
23.18


ATOM
1101
ND2
ASN
203
44.934
14.566
14.390
1.00
12.62


ATOM
1102
C
ASN
203
44.473
11.205
14.338
1.00
19.00


ATOM
1103
O
ASN
203
45.457
11.116
13.611
1.00
27.47


ATOM
1104
N
THR
204
44.518
10.882
15.628
1.00
19.90


ATOM
1105
CA
THR
204
45.765
10.433
16.249
1.00
19.76


ATOM
1106
CB
THR
204
45.691
10.527
17.761
1.00
19.43


ATOM
1107
OG1
THR
204
45.409
11.862
18.129
1.00
23.03


ATOM
1108
CG2
THR
204
47.001
10.115
18.364
1.00
22.47


ATOM
1109
C
THR
204
46.119
9.008
15.851
1.00
20.39


ATOM
1110
O
THR
204
47.300
8.673
15.663
1.00
11.64


ATOM
1111
N
HIS
205
45.079
8.179
15.716
1.00
15.29


ATOM
1112
CA
HIS
205
45.246
6.793
15.329
1.00
12.93


ATOM
1113
CB
HIS
205
43.890
6.119
15.303
1.00
9.41


ATOM
1114
CG
HIS
205
43.960
4.648
15.077
1.00
11.32


ATOM
1115 
CD2
HIS
205
45.012
3.796
15.056
1.00
12.67


ATOM
1116
ND1
HIS
205
42.842
3.881
14.841
1.00
11.26


ATOM
1117
CE1
HIS
205
43.198
2.616
14.686
1.00
11.39


ATOM
1118
NE2
HIS
205
44.509
2.536
14.810
1.00
10.23


ATOM
1119
C
HIS
205
45.914
6.731
13.954
1.00
14.03


ATOM
1120
O
HIS
205
46.788
5.912 
13.711
1.00
17.30


ATOM
1121
N
LEU
206
45.471
7.605
13.063
1.00
17.93


ATOM
1122
CA
LEU
206
45.988
7.715
11.705
1.00
20.38


ATOM
1123
CB
LEU
206
45.030
8.552
10.837
1.00
15.00


ATOM
1124
CG
LEU
206
43.611
7.985
10.669
1.00
17.79


ATOM
1125
CD1
LEU
205
42.902
8.815
9.643
1.00
16.39


ATOM
1126
CD2
LEU
206
43.606
6.519
10.256
1.00
7.72


ATOM
1127
C
LEU
206
47.394
8.333
11.670
1.00
22.16


ATOM
1128
O
LEU
206
48.200
7.964
10.811
1.00
26.75


ATOM
1129
N
LEU
207
47.652
9.315
12.541
1.00
18.99


ATOM
1130
CA
LEU
207
48.959
9.965
12.637
1.00
17.75


ATOM
1131
CB
LEU
207
48.953
11.016
13.716
1.00
18.85


ATOM
1132
CG
LEU
207
48.829
12.451
13.261
1.00
26.70


ATOM
1133
CD1
LEU
207
48.941
13.280
14.541
1.00
20.06


ATOM
1134
CD2
LEU
207
49.924
12.829
12.198
1.00
20.90


ATOM
1135
C
LEU
207
49.982
8.960
13.077
1.00
19.69


ATOM
1136
O
LEU
207
51.156
9.075
12.767
1.00
25.73


ATOM
1137
N
LEU
208
49.534
8.035
13.901
1.00
20.55


ATOM
1138
CA
LEU
208
50.377
6.989
14.432
1.00
21.59


ATOM
1139
CG
LEU
208
49.719
6.449
15.683
1.00
22.51


ATOM
1140
CG
LEU
208
50.338
5.240
16.322
1.00
25.67


ATOM
1141
CD1
LEU
208
51.707
5.621
16.833
1.00
25.95


ATOM
1142
CD2
LEU
208
49.403
4.792
17.428
1.00
24.34


ATOM
1143
C
LEU
208
50.607
5.874
13.411
1.00
21.91


ATOM
1144
O
LEU
208
51.758
5.505
13.173
1.00
25.74


ATOM
1145
N
LEU
209
49.535
5.367
12.787
1.00
19.26


ATOM
1146
CA
LEU
209
49.635
4.286
11.777
1.00
16.77


ATOM
1147
CB
LEU
209
48.271
3.966
11.168
1.00
13.38


ATOM
1148
CG
LEU
209
47.330
3.000
11.874
1.00
13.06


ATOM
1149
CD1
LEU
209
45.921
3.206
11.379
1.00
7.67


ATOM
1150
CD2
LEU
209
47.779
1.568
11.664
1.00
14.89


ATOM
1151
C
LEU
209
50.621
4.596
10.639
1.00
16.38


ATOM
1152
O
LEU
209
51.370
3.721
10.183 
1.00
17.07


ATOM
1153
N
LYS
210
50.635
5.842
10.187 
1.00
13.88


ATOM
1154
CA
LYS
210
51.536
6.208
9.123
1.00
14.30


ATOM
1155
CB
LYS
210
51.220
7.624
8.603
1.00
11.99


ATOM
1156
CG
LYS
210
51.477
8.779
9.526
1.00
7.35


ATOM
1157
CD
LYS
210
52.797
9.443
9.221
1.00
6.42


ATOM
1158
CE
LYS
210
53.002
10.669
10.085
1.00
6.47


ATOM
1159
NZ
LYS
210
53.263
10.313
11.513
1.00
14.19


ATOM
1160
C
LYS
210
53.008
6.020
9.523
1.00
17.24


ATOM
1161
O
LYS
210
53.845
5.688
8.670
1.00
21.95


ATOM
1162
N
ASP
211
53.306
6.139
10.819
1.00
19.90


ATOM
1163
CA
ASP
211
54.670
5.983
11.336
1.00
16.45


ATOM
1164
CB
ASP
211
54.685
6.109
12.854
1.00
11.34


ATOM
1165
CG
ASP
211
54.823
7.529
13.326
1.00
13.51


ATOM
1166
OD1
ASP
211
55.048
8.445
12.522
1.00
11.47


ATOM
1167
OD2
ASP
211
54.742
7.740
14.545
1.00
19.85


ATOM
1168
C
ASP
211
55.219
4.628
10.945 
1.00
16.72


ATOM
1169
O
ASP
211
56.424
4.461
10.749
1.00
21.07


ATOM
1170
N
ALA
212
54.307
3.679
10.778
1.00
15.96


ATOM
1171
CA
ALA
212
54.638
2.317
10.395
1.00
13.35


ATOM
1172
CB
ALA
212
53.406
1.453
10.450
1.00
9.60


ATOM
1173
C
ALA
212
55.246
2.251
9.001
1.00
17.10


ATOM
1174
O
ALA
212
56.055
1.368
8.735
1.00
21.49


ATOM
1175
N
GLN
213
54.860
3.181
8.122
1.00
17.33


ATOM
1176
CA
GLN
213
55.345
3.228
6.740
1.00
14.16


ATOM
1177
CB
GLN
213
54.295
3.896
5.838
1.00
13.57


ATOM
1178
CG
GLN
213
52.895
3.233
5.913
1.00
8.05


ATOM
1179
CD
GLN
213
52.956
1.733
5.680
1.00
9.09


ATOM
1180
OE1
GLN
213
53.641
1.288
4.777
1.00
13.24


ATOM
1181
NE2
GLN
213
52.284
0.950
6.518
1.00
7.38


ATOM
1182
C
GLN
213
56.681
3.948
6.661
1.00
17.76


ATOM
1183
O
GLN
213
57.479
3.716
5.752
1.00
22.36


ATOM
1184
N
VAL
214
56.918
4.838
7.614
1.00
16.49


ATOM
1185
CA
VAL
214
58.181
5.567
7.689
1.00
16.94


ATOM
1186
CB
VAL
214
58.008
6.922
8.418
1.00
17.23


ATOM
1187
CG1
VAL
214
59.328
7.615
8.598
1.00
17.53


ATOM
1188
CG2
VAL
214
57.076
7.809
7.631
1.00
17.23


ATOM
1189
C
VAL
214
59.261
4.731
6.396
1.00
15.03


ATOM
1190
O
VAL
214
60.314
4.506
7.833
1.00
12.50


ATOM
1191
N
PHE
215
58.961
4.188
9.576
1.00
18.28


ATOM
1192
CA
PHE
215
59.943
3.422
10.350
1.00
13.37


ATOM
1193
CB
PHE
215
59.892
3.849
11.805
1.00
14.35


ATOM
1194
CG
PHE
215
60.044
5.306
12.011
1.00 
12.08


ATOM
1195
CD1
PHE
215
58.932
6.092
12.281
1.00
13.84


ATOM
1196
CD2
PHE
215
61.284
5.903
11.895
1.00
11.02


ATOM
1197
CE1
PHE
215
59.052
7.459
12.125
1.00
11.98


ATOM
1198
CE2
PHE
215
61.420
7.264
12.038
1.00
16.66


ATOM
1199
CZ
PHE
215
60.294
8.052
12.302
1.00
17.15


ATOM
1200
C
PHE
215
59.854
1.906
10.141
1.00
15.97


ATOM
1201
O
PHE
215
60.826
1.243
10.675
1.00
19.35


ATOM
1202
N
GLY
216
58.700
1.355
9.981
1.00
16.28


ATOM
1203
CA
GLY
216
58.505
−0.087
9.975
1.00
16.57


ATOM
1204
C
GLY
216
59.707
−0.955
9.654
1.00
21.88


ATOM
1205
O
GLY
216
60.073
−1.849
10.433
1.00
19.41


ATOM
1206
N
GLU
217
60.342
−0.672
8.521
1.00
24.90


ATOM
1207
CA
GLU
217
61.488
−1.439
8.085
1.00
28.00


ATOM
1208
CB
GLU
217
61.919
−1.027
6.668
1.00
35.93


ATOM
1209
CG
GLU
217
63.039
−1.914
6.183
1.00
51.31


ATOM
1210
CD
GLU
217
63.279
−1.749
4.683
1.00
59.93


ATOM
1211
OE1
GLU
217
62.298
−1.817
3.904
1.00
65.77


ATOM
1212
OE2
GLU
217
64.456
−1.556
4.302
1.00
68.04


ATOM
1213
C
GLU
217
62.679
−1.407
9.025
1.00
27.28


ATOM
1214
O
GLU
217
63.299
−2.446
9.260
1.00
31.56


ATOM
1215
N
GLU
218
63.029
−0.126
9.535
1.00
22.80


ATOM
1216
CA 
GLU
218
64.149
−0.126
10.462
1.00
19.69


ATOM
1217
CB
GLU
218
64.705
1.302
10.527
1.00
19.03


ATOM
1218
CG
GLU
218
63.743
2.371
10.982
1.00
23.93


ATOM
1219
CD
GLU
218
64.270
3.783
10.738
1.00
31.49


ATOM
1220
OE1
GLU
218
64.001
4.706
11.543
1.00
29.38


ATOM
1221
OE2
GLU
218
64.949
3.977
9.718
1.00
38.81


ATOM
1222
C
GLU
218
63.794
−0.646
11.850
1.00
17.19


ATOM
1223
O
GLU
218
64.669
0.990
12.608
1.00
25.19


ATOM
1224
N
TRP
219
62.514
−0.735
12.168
1.00
13.68


ATOM
1225
CA
TRP
219
62.078
−1.230
13.452
1.00
11.22


ATOM
1226
CB
TRP
219
60.638
−0.816
13.740
1.00
15.63


ATOM
1227
CG 
TRP
219
60.475
0.563
14.192
1.00
19.27


ATOM
1228
CD2
TRP
219
59.249
1.297
14.263
1.00
17.84


ATOM
1229
CE2
TRP
219
59.555
2.568
14.791
1.00
16.01


ATOM
1230
CE3
TRP
219
57.918
1.000
13.924
1.00
22.82


ATOM
1231
CD1
TRP
219
61.450
1.395
14.658
1.00
20.82


ATOM
1232
NE1
TRP
219
60.903
2.600 
15.021
1.00
21.26


ATOM
1233
CZ2
TRP
219
58.589
3.547 
14.992
1.00
17.84


ATOM
1234
CZ3
TRP
219
56.945
1.982
14.121
1.00
20.61


ATOM
1235
CH2
TRP
219
57.289
3.238
14.651
1.00
24.23


ATOM
1236
C
TRP
219
62.093
2.729
13.468
1.00
12.69


ATOM
1237
O
TRP
219
61.905
−3.326
14.498
1.00
20.36


ATOM
1238
N
GLY
220
62.215
−3.370
12.331
1.00
14.83


ATOM
1239
CA
GLY
220
62.209
−4.816
12.384
1.00
15.91


ATOM
1240
C
GLY
220
60.923
−5.447
11.862
1.00
19.27


ATOM
1241
O
GLY
220
60.858
−6.662
11.767
1.00
23.97


ATOM
1242
N
TYR
221
59.884
−4.679
11.563
1.00
13.12


ATOM
1243
CA
TYR
221
58.684
−5.297
11.010
1.00
15.79


ATOM
1244
CB
TYR
221
57.579
−4.281
10.897
1.00
14.40


ATOM
1245
CG
TYR
221
56.915
−3.953
12.186
1.00
13.85


ATOM
1246
CD1
TYR
221
56.823
−2.645
12.607
1.00
15.85


ATOM
1247
CE1
TYR
221
56.110
−2.315
13.725
1.00
17.59


ATOM
1248
CD2
TYR
221
56.281
−4.941
12.939
1.00
13.29


ATOM
1249
CE2
TYR
221
55.564
−4.523
14.063
1.00
14.03


ATOM
1250
CZ
TYR
221
55.489
−3.301
14.443
1.00
16.10


ATOM
1251
OH
TYR
221
54.791
−2.942
15.554
1.00
26.08


ATOM
1252
C
TYR
221
58.972
−5.817
9.595
1.00
20.08


ATOM
1253
O
TYR
221
59.828
−5.291
8.905
1.00
25.54


ATOM
1254
N
SER
222
58.253
−6.832
9.140
1.00
22.90


ATOM
1255
CA
SER
222
58.481
−7.354
7.790
1.00
25.01


ATOM
1256
CB
SER
222
58.412
−8.881
7.807
1.00
25.19


ATOM
1257
OG
SER
222
57.154
−9.300
8.332
1.00
30.91


ATOM
1258
C
SER
222
57.437
−6.787
6.818
1.00
23.30


ATOM
1259
O
SER
222
56.534
−6.062
7.241
1.00
24.16


ATOM
1260
N
SER
223
57.542
−7.159
5.539
1.00
24.20


ATOM
1261
CA
SER
223
56.613
−6.705
4.486
1.00
22.69


ATOM
1262
CB
SER
223
56.827
−7.473
3.162
1.00
25.01


ATOM
1263
OG
SER
223
57.699
−6.777
2.293
1.00
30.78


ATOM
1264
C
SER
223
55.178
−6.832
4.910
1.00
18.96


ATOM
1265
O
SER
223
54.408
−5.924
4.904
1.00
24.83


ATOM
1266
N
GLU
224
54.849
−8.100
5.331
1.00
14.34


ATOM
1267
CA
GLU
224
53.510
−8.430
5.768
1.00
14.70


ATOM
1268
CB
GLU
224
53.452
−9.881
6.241
1.00
11.94


ATOM
1269
CD
GLU
224
53.594
−10.917
5.139
1.00
6.62


ATOM
1270
CD
GLU
224
55.008
−11.084
4.574
1.00
11.92


ATOM
1271
OE1
GLU
224
56.032
−10.939
5.277
1.00
17.07


ATOM
1272
PE2
GLU
224
55.100
−11.431
3.392
1.00
19.14


ATOM
1273
C
GLU
224
53.020
7.494
6.860
1.00
16.93


ATOM
1274
O
GLU
224
51.982
−6.859
6.719
1.00
23.58


ATOM
1275
N
ASP
225
53.794
−7.368
7.928
1.00
21.13


ATOM
1276
CA
ASP
225
53.423
−6.518
9.037
1.00
14.44


ATOM
1277
CB
ASP
225
54.554
−6.451
10.050
1.00
20.030


ATOM
1278
CG
ASP
225
54.686
−7.712
10.863
1.00
22.22


ATOM
1279
OD1
ASP
225
53.700
−8.071
11.531
1.00
22.32


ATOM
1280
OD2
ASP
225
55.782
−8.315
10.861
1.00
18.56


ATOM
1281
C
ASP
225
53.156
−5.127
8.534
1.00
19.11


ATOM
1282
O
ASP
225
52.081
−4.583
8.761
1.00
22.45


ATOM
1283
N
VAL
226
54.130
−4.547
7.843
1.00
17.57


ATOM
1284
CA
VAL
226
53.972
−3.206
7.332
1.00
18.36


ATOM
1285
CB
VAL
226
55.266
−2.702
6.681
1.00
17.30


ATOM
1286
CG1
VAL
226
55.029
−1.374
6.029
1.00
16.11


ATOM
1287
CG2
VAL
226
56.345
−2.540
7.739
1.00
16.32


ATOM
1288
C
VAL
226
52.762
−3.050
6.392
1.00
20.92


ATOM
1289
O
VAL
226
52.072
−2.031
6.467
1.00
24.32


ATOM
1290
N
ALA
227
52.472
−4.051
5.551
1.00
19.82


ATOM
1291
CA
ALA
227
51.314
3.986
4.634
1.00
19.35


ATOM
1292
CB
ALA
227
51.397
−5.063
3.574
1.00
15.70


ATOM
1293
C
ALA
227
49.962
−4.081
5.380
1.00
19.98


ATOM
1294
O
ALA
227
48.943
−3.530
4.945
1.00
21.24


ATOM
1295
N
GLU
228
49.947
−4.797
6.493
1.00
16.52


ATOM
1296
CA
GLU
228
48.735
−4.905
7.275
1.00
15.88


ATOM
1297
CB
GLU
228
48.932
−5.920
8.395
1.00
18.82


ATOM
1298
CG
GLU
228
48.725
−7.341
7.906
1.00
23.82


ATOM
1299 
CD
GLU
228
49.723
−8.330
8.473
1.00
28.53


ATOM
1300
OE1
GLU
228
50.241
−9.159
7.694
1.00
30.67


ATOM
1301
OE2
GLU
228
49.979
31 8.296
9.692
1.00
32.83


ATOM
1302
C
GLU
228
48.381
−3.535
7.812
1.00
12.58


ATOM
1303
O
GLU
228
47.222
−3.150
7.817
1.00
15.95


ATOM
1304
N
PHE
229
49.398
−2.785
8.222
1.00
13.17


ATOM
1305
CA
PHE
229
49.207
−1.438
8.730
1.00
13.77


ATOM
1306
CB
PHE
229
50.512
0.911
9.340
1.00
13.96


ATOM
1307
CG
PHE
229
50.856
−1.526
10.682
1.00
12.34


ATOM
1308
CD1
PHE
229
52.140
−2.010
10.944
1.00
12.39


ATOM
1309
CD2
PHE
229
49.890
−1.636
11.686
1.00
12.04


ATOM
1310
CE1
PHE
229
52.454
−2.597
12.171
1.00
8.60


ATOM
1311
CE2
PHE
229
50.207
−2.224
12.928
1.00
9.34


ATOM
1312
CZ
PHE
229
51.479
−2.701
13.164
1.00
6.27


ATOM
1313
C
PHE
229
48.698
−0.501
7.623
1.00
16.58


ATOM
1314
O
PHE
229
47.732
0.240
7.829
1.00
17.11


ATOM
1315
N
TYR
230
49.321
−0.545
6.443
1.00
17.83


ATOM
1316
CA
TYR
230
48.889
0.306
5.308
1.00
18.63


ATOM
1317
CB
TYR
230
49.775
0.095
4.085
1.00
17.05


ATOM
1318
CG
TYR
230
49.660
1.160
3.027
1.00
19.90


ATOM
1319
CD1
TYR
230
50.175
2.435
3.245
1.00
20.56


ATOM
1320
CE1
TYR
230
50.141
3.410
2.266
1.00
17.60


ATOM
1321
CD2
TYR
230
49.092
0.887
1.786
1.00
20.54


ATOM
1322
CE2
TYR
230
49.048
1.858
0.798
1.00
21.92


ATOM
1323
CZ
TYR
230
49.583
3.121
1.047
1.00
24.08


ATOM
1324
OH
TYR
230
49.569
4.100
0.079
1.00
22.12


ATOM
1325
C
TYR
230
47.452
−0.014
4.941
1.00
14.05


ATOM
1326
O
TYR
230
46.630
0.873
4.867
1.00
18.48


ATOM
1327
N
HIS
231
47.152
−1.288
4.724
1.00
15.20


ATOM
1328
CA
HIS
231
45.789
−1.698
4.408
1.00
16.34


ATOM
1329
CB
HIS
231
45.657
−3.218
4.400
1.00
19.85


ATOM
1330
CG
HIS
231
46.101
−3.869
3.126
1.00
27.74


ATOM
1331
CD2
HIS
231
47.267
−3.787
2.433
1.00
30.71


ATOM
1332
ND1
HIS
231
45.308
−4.754
2.423
1.00
28.38


ATOM
1333
CE1
HIS
231
45.963
−5.185
1.361
1.00
29.98


ATOM
1334
NE2
HIS
231
47.155
−4.612
1.143
1.00
22.31


ATOM
1335
C
HIS
231
44.846
−1.125
5.466
1.00
18.40


ATOM
1336
O
HIS
231
43.840
−0.507
5.141
1.00
27.16


ATOM
1337
N
ARG
232
45.192
−1.281
6.735
1.00
18.07


ATOM
1338
CA
ARG
232
44.354
−0.766
7.806
1.00
15.74


ATOM
1339
CB
ARG
232
44.940
−1.137
9.171
1.00
22.99


ATOM
1340
CG
ARG
232
44.049
−0.764
10.379
1.00
22.30


ATOM
1341
CD
ARG
232
44.601
−1.380
11.641
1.00
25.70


ATOM
1342
NE
ARG
232
44.646
−2.838
11.520
1.00
33.18


ATOM
1343
CZ 
ARG
232
45.690
−3.613
11.826
1.00
33.26


ATOM
1344
NH1
ARG
232
46.835
−3.093
12.292
1.00
22.03


ATOM
1345
NH2
ARG
232
45.572
−4.932
11.656
1.00
35.05


ATOM
1346
C
ARG
232
44.202
0.738
7.727
1.00
17.28


ATOM
1347
O
ARG
232
43.099
1.246
7.931
1.00
15.75


ATOM
1348
N
GLN
233
45.300
1.448
7.431
1.00
16.95


ATOM
1349
CA
GLN
233
45.272
2.903
7.343
1.00
10.93


ATOM
1350
CB
GLN
233
46.656
3.455
7.062
1.00
12.92


ATOM
1351
CG
GLN
233
46.688
4.957
6.820
1.00
7.74


ATOM
1352
CD
GLN
233
48.094
5.496
6.787
1.00
9.89


ATOM
1353
OE1
GLN
233
49.047
4.762
6.991
1.00
7.65


ATOM
1354
NE2
GLN
233
48.227
6.795
6.601
1.00
10.54


ATOM
1355
C
GLN
233
44.310
3.360
6.264
1.00
15.42


ATOM
1356
O
GLN
233
41.520
4.295
6.480
1.00
17.48


ATOM
1357
N
LEU
234
44.360
2.707
5.104
1.00
11.75


ATOM
1358
CA
LEU
234
43.467
3.080
4.016
1.00
11.38


ATOM
1359
CB
LEU
234
43.788
2.276
2.753
1.00
15.07


ATOM
1360
CG
LEU
234
45.197
2.340
2.165
1.00
16.15


ATOM
1361
CD1
LEU
234
45.214
1.734
0.753
1.00
16.02


ATOM
1362
CD2
LEU
234
45.639
3.778
2.121
1.00
15.26


ATOM
1363
C
LEU
234
42.003
2.849
4.420
1.00
12.48


ATOM
1364
O
LEU
234
41.157
3.716
4.243
1.00
19.53


ATOM
1365
N
LYS
235
41.727
1.681
4.982
1.00
13.76


ATOM
1366
CA
LYS
235
40.396
1.277
5.413
1.00
15.08


ATOM
1367
CB
LYS
235
40.483
−0.131
5.970
1.00
20.96


ATOM
1368
CG
LYS
235
39.259
−0.982
5.768
1.00
30.47


ATOM
1369
CD
LYS
235
39.452
−2.367
6.394
1.00
40.95


ATOM
1370
CE
LYS
235
40.776
−3.043
5.947
1.00
49.89


ATOM
1371
NZ 
LYS
235
41.705
−3.351
7.117
1.00
50.92


ATOM
1372
C
LYS
235
39.802
2.186
6.470
1.00
18.56


ATOM
1373
O
LYS
235
38.613
2.442
6.462
1.00
22.95


ATOM
1374
N
LEU
236
40.619
2.649
7.410
1.00
21.51


ATOM
1375
CA
LEU
236
40.134
3.538
8.462
1.00
14.99


ATOM
1376
CB
LEU
236
41.000
3.415
9.708
1.00
19.28


ATOM
1377
CG
LEU
236
40.947
1.987
10.248
1.00
17.90


ATOM
1378
CD1
LEU
236
41.728
1.869
11.495
1.00
22.07


ATOM
1379
CD2
LEU
236
39.531
1.624
10.530
1.00
21.26


ATOM
1380
C
LEU
236
40.028
4.981
8.019
1.00
17.01


ATOM
1381
O
LEU
236
39.148
5.701
8.477
1.00
20.51


ATOM
1382
N
THR
237
40.907
5.427
7.129
1.00
16.17


ATOM
1383
CA
THR
237
40.806
6.803
6.642
1.00
15.50


ATOM
1384
CB
THR
237
41.824
7.070
5.543
1.00
15.39


ATOM
1385
OG1
THR
237
43.144
6.962
6.077
1.00
17.24


ATOM
1386
CG2
THR
237
41.627
8.446
4.968
1.00
16.40


ATOM
1387
C
THR
237
39.414
6.972
6.023
1.00
20.09


ATOM
1388
O
THR 
237
38.776
8.002
6.162
1.00
20.01


ATOM
1389
N
GLN
238
38.960
5.933
5.343
1.00
23.44


ATOM
1390
CA
GLN
238
37.670
5.946
4.714
1.00
24.58


ATOM
1391
CB
GLN
238
37.559
4.775
3.738
1.00
24.07


ATOM
1392
CG
GLN
238
36.197
4.628
3.068
1.00
28.51


ATOM
1393
CD
GLN
238
35.322
3.583
3.724
1.00
31.81


ATOM
1394
OE1
GLN 
238
34.185
3.857
4.136
1.00
34.84


ATOM
1395
NE2
GLN
238
35.840
2.367
3.816
1.00
34.59


ATOM
1396
C
GLN
238
36.614
5.861
5.801
1.00
26.68


ATOM
1397
O
GLN
238
35.709
6.685
5.655
1.00
28.24


ATOM
1398
N
GLN
239
36.750
4.869
6.693
1.00
28.41


ATOM
1399
CA
GLN
239
35.777
4.718
7.768
1.00
25.98


ATOM
1400
CB
GLN
239
36.138
3.536
8.644
1.00
34.27


ATOM
1401
CG
GLN
239
35.788
2.203
8.062
1.00
42.96


ATOM
1402
CD
GLN
239
35.792
1.116
9.118
1.00
51.22


ATOM
1403
OE1
GLN
239
35.586
1.383
10.318
1.00
51.30


ATOM
1404
NE2
GLN
239
36.012
−0.118
8.685
1.00
54.93


ATOM
1405
C
GLN
239
35.585
5.933
8.644
1.00
22.06


ATOM
1406
O
GLN
239
34.460
6.397
8.793
1.00
24.27


ATOM
1407
N
TYR
240
36.669
6.420
9.257
1.00
22.64


ATOM
1408
CA
TYR
240
36.626
7.607
10.139
1.00
20.71


ATOM
1409
CB
TYR
240
38.010
7.923
10.729
1.00
16.77


ATOM
1410
CG
TYR
240
38.518
6.840
11.637
1.00
17.42


ATOM
1411
CD1
TYR
240
37.821
6.001
12.432
1.00
17.36


ATOM
1412
CE1
TYR
240
38.400
5.024
13.262
1.00
17.77


ATOM
1413
CD2
TYR
240
40.004
6.667
11.703
1.00
19.31


ATOM
1414
CE2
TYR
240
40.585
5.698
12.525
1.00
19.41


ATOM
1415
CZ
TYR
240
39.781
4.881
13.295
1.00
19.35


ATOM
1416
OH
TYR
240
40.373
3.873
14.031
1.00
19.37


ATOM
1417
C
TYR 
240
36.038
8.858
9.463
1.00
19.71


ATOM
1418
O
TYR 
240
35.248
9.588
10.077
1.00
18.91


ATOM
1419
N
THR 
241
36.422
9.082
8.205
1.00
20.29


ATOM
1420
CA
THR
241
35.938
10.195
7.397
1.00
16.59


ATOM
1421
CB
THR
241
36.619
10.194
5.995
1.00
21.67


ATOM
1422
OG1
THR
241
38.003
10.546
6.133
1.00
19.88


ATOM
1423
CG2
THR
241
35.923
11.168
4.990
1.00
20.34


ATOM
1424
C
THR
241
34.427
10.065
7.222
1.00
16.73


ATOM
1425
O
THR
241
33.672
10.988
7.536
1.00
20.54


ATOM
1426
N
ASP
242
33.982
8.916
6.734
1.00
17.09


ATOM
1427
CA
ASP
242
32.563
8.690
6.533
1.00
21.69


ATOM
1428
CB
ASP
242
32.299
7.300
5.954
1.00
21.39


ATOM
1429
CG
ASP
242
32.603
7.197
4.465
1.00
20.65


ATOM
1430
OD1
ASP
242
32.855
8.232
3.813
1.00
18.80


ATOM
1431
OD2
ASP
242
32.575
6.058
3.951
1.00
19.59


ATOM
1432
C
ASP
242
31.790
8.839
7.847
1.00
25.51


ATOM
1433
O
ASP
242
30.699
9.423
7.855
1.00
28.83


ATOM
1434
N
HIS 
243
32.344
8.354
8.961
1.00
21.95


ATOM
1435
CA
HIS
243
31.615
8.463
10.220
1.00
18.92


ATOM
1436
CB
HIS
243
32.309
7.708
11.352
1.00
17.61


ATOM
1437
CG
HIS
243
31.690
7.935
12.700
1.00
12.62


ATOM 
1438
CD2
HIS
243
31.795
8.970
13.562
1.00
14.95


ATOM
1439
ND1
HIS
243
30.935
6.981
13.349
1.00
16.29


ATOM
1440
CE1
HIS
243
30.620 
7.411
14.557
1.00
9.95


ATOM
1441
NE2
HIS 
243
31.130
8.616
14.709
1.00
16.91


ATOM
1442
C
HIS
243
31.383
9.904
10.628
1.00
21.10


ATOM
1443
O
HIS 
243
30.301
10.249
11.070
1.00
25.20


ATOM
1444
N
CYS
244
32.413
10.734
10.539
1.00
20.17


ATOM
1445
CA
CYS
244
32.271
12.128
10.916
1.00
20.48


ATOM
1446
CB
CYS
244
33.624
12.819
10.883
1.00
18.34


ATOM
1447
SG
CYS
244
34.760
12.105
12.050
1.00
16.47


ATOM
1448
C
CYS
244
31.269
12.890
10.058
1.00
21.21


ATOM
1449
O
CY5
244
30.462
13.654
10.570
1.00
22.28


ATOM
1450
N
VAL
245
31.312
12.683
8.746
1.00
22.25


ATOM
1451
CA
VAL
245
30.395
13.376
7.841
1.00
22.33


ATOM
1452
CB
VAL
245
30.781
13.140
6.359
1.00
19.16


ATOM
1453
CG1
VAL
245
29.816
13.827
5.443
1.00
21.10


ATOM
1454
CG2
VAL
245
32.171
13.691
6.093
1.00
17.45


ATOM
1455
C
VAL
245
28.957
12.942
8.113
1.00
21.40


ATOM
1456
O
VAL
245
28.055
13.770
8.214
1.00
22.33


ATOM
1457
N
ASN
246
28.780
11.651
8.348
1.00
21.90


ATOM
1458
CA
ASN
246
27.477
11.063
8.620
1.00
23.19


ATOM
1459
CB
ASN
246
27.639
9.557
8.771
1.00
34.68


ATOM
1460
CG
ASN
246
26.366
8.855
9.237
1.00
44.33


ATOM
1461
OD1
ASN
246
25.741
9.220
10.248
1.00
48.73


ATOM
1462
ND2
ASN
246
26.015
7.790
8.530
1.00
50.65


ATOM
1463
C
ASN
246
26.790
11.631
9.854
1.00
22.82


ATOM
1464
O
ASN
246
25.626 
12.038
9.797 
1.00
24.79


ATOM
1465
N
TRP
247
27.487
11.615
10.981
1.00
20.19


ATOM
1466
CA
TRP
247
26.906
12.120
12.208
1.00
18.58


ATOM
1467
CG
TRP
247
27.694
11.620
13.418
1.00
17.89


ATOM
1468
CG
TRP
247
27.467
10.185
13.549
1.00
21.14


ATOM
1469
CD2
TRP
247
26.199
9.532
13.782
1.00
22.32


ATOM
1470
CE2
TRP
247
26.388
8.158
13.537
1.00
22.60


ATOM
1471
CE3
TRP
247
24.920
9.982
14.167
1.00
22.25


ATOM
1472
CD1
TRP
247
28.337
9.210
13.222
1.00
23.88


ATOM
1473
NE1
TRP
247
27.701
7.991
13.194
1.00
25.03


ATOM
1474
CZ2
TRP
247
25.348
7.214
13.659
1.00
22.59


ATOM
1475
CZ3
TRP
247
23.883
9.045
11.289
1.00
15.92


ATOM
1476
CH2
TRP
247
24.107
7.679
14.036
1.00
21.52


ATOM
1477
C
TRP
247
26.734
13.619
12.203
1.00
21.26


ATOM
1478
O
TRP
247
25.872
14.151
12.888
1.00
23.07


ATOM
1479
N
TYR
248
27.530
14.291
11.385
1.00
22.21


ATOM
1480
CA
TYR
248
27.469
15.733
11.270
1.00
19.44


ATOM
1481
CB
TYR
248
28.634
16.262
10.397
1.00
22.06


ATOM
1482
CG
TYR
248
28.500
17.715
9.992
1.00
15.39


ATOM
1483
CD1
TYR
248
28.656
18.733
10.924
1.00
18.30


ATOM
1484
CE1
TYR
248
28.429
20.049
10.589
1.00
19.55


ATOM
1485
CD2
TYR
248
28.120
18.059
8.700
1.00
17.91


ATOM
1486
CE2
TYR
248
27.883
19.376
8.354
1.00
15.27


ATOM
1487
CZ
TYR
248
28.037
20.369
9.299
1.00
17.78


ATOM
1488
OH
TYR
248
27.793
21.684
8.965
1.00
25.83


ATOM
1489
C
TYR
248
26.158
16.041
10.611
1.00
20.61


ATOM
1490
O
TYR
248
25.378
16.842
11.111
1.00
22.05


ATOM
1491
N
ASN
249
25.892
15.369
9.500
1.00
23.02


ATOM
1492
CA
ASN
249
24.664
15.626
8.778
1.00
23.67


ATOM
1493
CB
ASN
249
24.597
14.835
7.483
1.00
21.11


ATOM
1494
CG
ASN
249
25.513
15.393
6.422
1.00
22.16


ATOM
1495
OD1
ASN
249
25.870
16.560
6.461
1.00
29.65


ATOM
1496
ND2
ASN
249
25.918
14.556
5.478
1.00
23.60


ATOM
1497
C
ASN
249
23.490
15.315
9.655
1.00
25.98


ATOM
1498
O
ASN
249
22.552
16.119
9.737
1.00
28.81


ATOM
1499
N
VAL
250
23.501
14.197
10.378
1.00
25.43


ATOM
1500
CA
VAL
250
22.507
13.792
11.270
1.00
23.20


ATOM
1501
CB
VAL
250
22.777
12.430
11.913
1.00
22.17


ATOM
1502
CG1
VAL
250
21.826 
12.188
13.069
1.00
17.43


ATOM
1503
CG2 
VAL
250
22.594
11.343
10.894
1.00
18.80


ATOM
1504
C
VAL
250
22.247
14.833
12.345
1.00
25.76


ATOM
1505
O
VAL
250
21.101
15.166
12.599
1.00
34.35


ATOM
1506
N
GLY
251
23.292
15.373
12.955
1.00
24.96


ATOM
1507
CA
GLY
251
23.092
16.373
13.986
1.00
23.97


ATOM
1508
C
GLY
251
22.657
17.701
13.402
1.00
28.06


ATOM
1509
O
GLY
251
21.793
18.396
13.947
1.00
31.01


ATOM
1510
N
LEU
252
23.273
18.070
12.290
1.00
29.10


ATOM
1511
CA
LEU
252
22.957
19.321
11.628
1.00
28.66


ATOM
1512
CB
LEU
252
23.704
19.424
10.309
1.00
23.77


ATOM
1513
CD1
LEU
252
23.320
20.699
9.575
1.00
22.56


ATOM
1514
CD1
LEU
252
23.869
21.892
10.323
1.00
26.59


ATOM
1515
CD2
LEU
252
23.816
20.672
8.152
1.00
24.48


ATOM
1516
C
LEU
252
21.474
19.391
11.342
1.00
30.41


ATOM 
1517
O
LEU
252
20.801
20.344
11.716
1.00
32.91


ATOM
1518
N
ASN
253
20.966
18.347
10.711
1.00
30.60


ATOM
1519
CA
ASN
253
19.569
18.295
10.351
1.00
33.65


ATOM
1520
CB
ASN
253
19.316
17.160
9.372
1.00
35.63


ATOM
1521
CG
ASN
253
19.862
17.463
7.994
1.00
42.54


ATOM
1522
OD1
ASN
253
20.855
18.186
7.835
1.00
42.40


ATOM 
1523
ND2
ASN
253
19.203
16.930
6.981
1.00
50.55


ATOM
1524
C
ASN
253
18.599
18.235
11.507
1.00
33.58


ATOM
1525
O
ASN
253
17.414
18.515
11.336
1.00
37.79


ATOM
1526
N
GLY
254
19.085
17.900
12.693
1.00
31.74


ATOM
1527
CA
GLY
254
18.189
17.842
13.839
1.00
29.82


ATOM
1528
C
GLY
254
17.844
19.241
14.310
1.00
29.07


ATOM
1529
O
GLY
254
16.876
19.454
15.024
1.00
29.77


ATOM
1530
N
LEU
255
18.645
20.208
13.885
1.00
28.00


ATOM
1531
CA
LEU
255
18.448
21.586
14.269
1.00
26.04


ATOM
1532
CB
LEU
255
19.804
22.200
14.577
1.00
22.14


ATOM
1533
CG
LEU
255
20.563
21.304
15.563
1.00
27.96


ATOM
1534
CD1
LEU
255
22.068
21.563
15.626
1.00
26.56


ATOM
1535
CD2
LEU
255
19.938
21.483
16.905
1.00
27.86


ATOM 
1536
C
LEU
255
17.687
22.391
13.209
1.00
30.33


ATOM
1537
O
LEU
255
17.556
23.608
13.330
1.00
35.36


ATOM
1538
N
ARG
256
17.187
21.726
12.169
1.00
31.16


ATOM
1539
CA
ARG
256
16.436
22.438
11.145
1.00
32.82


ATOM
1540
CB
ARG
256
16.244
21.610
9.865
1.00
31.47


ATOM
1541
CG
ARG
256
17.508
21.568
9.000
1.00
35.00


ATOM
1542
CD
ARG
256
17.291
21.321
7.501
1.00
30.02


ATOM
1543
NE
ARG
256
18.344
22.019
6.759
1.00
34.65


ATOM
1544
CZ
ARG
256
19.515
21.489
6.394
1.00
40.31


ATOM
1545
NH1
ARG
256
20.404
22.236
5.758
1.00
47.05


ATOM
1546
NH2
ARG
256
19.788
20.205
6.587
1.00
44.05


ATOM
1547
C
ARG
256
15.106
22.738
11.775
1.00
36.39


ATOM
1548
O
ARG
256
14.455
21.844
12.325
1.00
39.88


ATOM
1549
N
GLY
257
14.772
24.020
11.792
1.00
37.32


ATOM
1550
CA
GLY
257
13.522
24.492
12.359
1.00
37.66


ATOM
1551
C
GLY
257
13.120
25.647
11.475
1.00
39.38


ATOM
1552
O
GLY
257
13.795
25.892
10.466
1.00
45.14


ATOM
1553
N
SER
258
12.069
26.377
11.830
1.00
39.54


ATOM
1554
CA
SER
258
11.625
27.496
10.989
1.00
40.17


ATOM
1555
CB
SER
258
10.131
27.380
10.721
1.00
39.14


ATOM
1556
OG
SER
258
9.461
27.094
11.930
1.00
43.54


ATOM
1557
C
SER
258
11.921
28.885
11.518
1.00
37.11


ATOM
1558
O
SER
258
11.872
29.862
10.779
1.00
35.66


ATOM
1559
N
THR
259
12.259
28.957
12.790
1.00
37.79


ATOM
1560
CA
THR
259
12.518
30.215
13.455
1.00
41.44


ATOM
1561
CB
THR
259
12.301
30.043
14.95
11.00
45.91


ATOM
1562
OG1
THR
259
11.504
28.874
15.180
1.00
55.55


ATOM
1563
CG2
THR
259
11.600
31.273
15.530
1.00
55.48


ATOM
1564
C
THR
259
13.899
30.826
13.285
1.00
38.35


ATOM
1565
O
THR
259
14.813
30.213
12.739
1.00
41.82


ATOM
1566
N
TYR
260
14.020
12.057
13.771
1.00
35.05


ATOM 
1567
CA
TYR
260
15.269
32.786
13.777
1.00
31.66


ATOM
1568
CB
TYR
260
15.049
34.194
14.305
1.00
26.91


ATOM
1569
CG
TYR
260
16.340
34.934
14.460
1.00
26.27


ATOM
1570
CD1
TYR
260
16.998
15.438
13.349
1.00
28.25


ATOM
1571
OE1
TYR
260
18.205
36.077
13.463
1.00
26.96


ATOM
1572
CD2
TYR
260
16.933
35.097
15.702
1.00
28.45


ATOM
1573
OE2
TYR
260
18.152
35.740
15.828
1.00
26.78


ATOM
1574
CZ
TYR
260
18.770
36.224
14.695
1.00
27.71


ATOM
1575
OH
TYR
260
19.957
36.878
14.774
1.00
36.80


ATOM
1576
C
TYR
260
16.160
32.065
14.773
1.00
34.78


ATOM
1577
O
TYR
260
17.357
31.917
14.557
1.00
37.21


ATOM 
1578
N
ASP
261
15.566
31.656
15.891
1.00
37.42


ATOM
1579
CA
ASP
261
16.295
30.961
16.942
1.00
40.44


ATOM
1580
CB
ASP
261
15.433
30.745
18.155
1.00
46.19


ATOM
1581
CG
ASP
261
16.204
30.322
19.386
1.00
52.07


ATOM
1582
OD1
ASP
261
17.336
30.836
19.573
1.00
55.53


ATOM
1583
OD2
ASP
261
15.692
29.482
20.159
1.00
54.28


ATOM
1584
C
ASP
261
16.734
29.626
16.411
1.00
40.15


ATOM
1585
O
ASP
261
17.853
29.195
16.644
1.00
40.37


ATOM
1586
N
ALA
262
15.823
28.974
15.697
1.00
40.43


ATOM
1587
CA
ALA
262
16.113
27.679
15.104
1.00
39.06


ATOM
1588
CB
ALA
262
14.936
27.183
14.297
1.00
36.99


ATOM
1589
C
ALA
262
17.324
27.863
14.209
1.00
38.56


ATOM
1590
O
ALA
262
18.222
27.031
14.213
1.00
42.67


ATOM
1591
N
TRP
263
17.372
28.972
13.475
1.00
34.48


ATOM
1592
CA
TRP
263
18.501
29.200
12.612
1.00
30.51


ATOM 
1593
CB
TRP
263
18.254
30.341
11.647
1.00
29.10


ATOM 
1594
CG
TRP
263
19.279
30.344
10.580
1.00
27.55


ATOM
1595
CD2
TRP
263
20.493
31.087
10.566
1.00
26.16


ATOM
1596
CE2
TRP
263
21.195
30.722 
9.389
1.00
27.70


ATOM
1597
CE3
TRP
263
21.063
32.022
11.434
1.00
25.40


ATOM
1598
CD1
TRP
263
19.281
29.586
9.447
1.00
30.08


ATOM
1599
NE1
TRP
263
20.429
29.803
8.727
1.00
25.78


ATOM
1600
CZ2
TRP
263
22.441
31.264
9.050
1.00
26.88


ATOM
1601
CZ3
TRP
263
22.307
32.565
11.105
1.00
32.51


ATOM
1602
CH2
TRP
263
22.986
32.178
9.912
1.00
33.60


ATOM
1603
C
TRP
263
19.800
29.438
13.372
1.00
31.82


ATOM
1604
O
TRP
263
20.761
28.703
13.176
1.00
33.27


ATOM
1605
N
VAL
264
19.838
30.415
14.269
1.00
29.96


ATOM
1606
CA
VAL
254
21.088
30.704
14.981
1.00
33.08


ATOM
1607
CB
VAL
264
20.955
31.885
15.992
1.00
35.92


ATOM
1608
CG1
VAL
264
20.488
33.142
15.272
1.00
35.34


ATOM
1609
CG2
VAL
264
19.991
31.534
17.130
1.00
40.92


ATOM
1610
C
VAL
264
21.726
29.488
15.651
1.00
33.22


ATOM
1611
O
VAL
264
22.948
29.417
15.762
1.00
33.90


ATOM
1612
N
LYS
265
20.907
28.521
16.059
1.00
33.23


ATOM
1613
CA
LYS
265
21.414
27.303
16.697
1.00
34.85


ATOM
1614
CB
LYS
265
20.343
26.643
17.564
1.00
37.37


ATOM
1615
CG
LYS
265
20.023
27.416
18.819
1.00
44.29


ATOM
1616
CD
LYS
265
19.068
26.626
19.676
1.00
55.75


ATOM
1617
CE
LYS
265
18.503
27.475
20.813
1.00
63.56


ATOM
1618
NZ
LYS
265
17.404
26.772
21.560
1.00
68.84


ATOM
1619 
C
LYS
265
21.912
26.317
15.652
1.00
32.74


ATOM
1620
O
LYS 
265
22.906
25.631
15.855
1.00
31.29


ATOM
1621
N
PHE 
266
21.189
26.259
14.545
1.00
30.50


ATOM
1622
CA
PHE
266
21.515
25.422
13.411
1.00
27.65


ATOM
1623
CB
PHE
266
20.411
25.601
12.373
1.00
23.05


ATOM
1624
CG
PHE
266
20.742
25.066
11.028
1.00
26.10


ATOM
1625
CD1
PHE
265
20.494
23.727
10.714
1.00
23.77


ATOM
1626
CD2
PHE
265
21.253
25.915
10.036
1.00
27.75


ATOM
1627
CE1
PHE
266
20.746
23.235
9.426
1.00
20.79


ATOM
1628
CE2
PHE
266
21.506
25.434
8.748
1.00
25.12


ATOM
1629
C2
PHE
266
21.247
24.079
8.447
1.00
20.14


ATOM
1630
C
PHE
266
22.868
25.865
12.843
1.00
28.95


ATOM
1631
O
PHE
266
23.705
25.034
12.494
1.00
33.21


ATOM
1632
N
ASN
267
23.080
27.177
12.769
1.00
27.02


ATOM
1633
CA
ASN
267
24.323
27.716
12.244
1.00
26.43


ATOM
1634
CB
ASN
267
24.175
29.175
11.812
1.00
25.78


ATOM
1635
CG
ASN
267
25.484
29.752
11.261
1.00
30.92


ATOM
1636
OD1
ASN
267
25.979
29.315
10.216
1.00
34.66


ATOM
1637
ND2
ASN
267
26.061
30.707
11.975
1.00
31.20


ATOM
1638
C
ASN
267
25.497
27.609
13.197
1.00
28.55


ATOM
1639
O
ASN
267
26.640
27.638
12.760
1.00
35.77


ATOM
1640
N
ARG
268
25.246
27.537
14.498
1.00
30.56


ATOM
1641
CA
ARG
268
26.345
27.433
15.452
1.00
26.63


ATOM
1642
CB
ARG
268
25.851
27.773
16.844
1.00
31.27


ATOM
1643
CG
ARG
268
26.959
28.125
17.764
1.00
42.83


ATOM
1644
CD
ARG
268
26.452
28.417
19.139
1.00
52.31


ATOM
1645
NE
ARG
268
27.563
28.446
20.076
1.00
61.73


ATOM
1646
C2
ARG
268
27.510
27.929
21.295
1.00
68.05


ATOM
1647
NH1
ARG
268
28.574
27.980
22.086
1.00
71.21


ATOM
1648
NE2
ARG
268
26.382
27.374
21.725
1.00
75.05


ATOM
1649
C
ARG
268
26.955
26.028
15.407
1.00
25.08


ATOM
1650
O
ARG
268
28.157
25.861
15.473
1.00
24.26


ATOM
1651
N
PHE
269
26.106
25.020
15.284
1.00
21.54


ATOM
1652
CA
PHE
269
26.547
23.645
15.194
1.00
20.29


ATOM
1653
CB
PHE
269
25.315
22.731
15.083
1.00
17.88


ATOM
1654
CG
PHE
269
25.631
21.252 
14.947
1.00
23.71


ATOM
1655
CD1
PHE
269
25.620
20.419
16.063
1.00
22.41


ATOM
1656
CD2
PHE
269
25.870
20.677
13.691
1.00
25.94


ATOM
1657
CE1
PHE
269
25.838
19.062
15.937
1.00
20.65


ATOM
1658
CE2
PHE
269
26.091
19.315
13.552
1.00
17.14


ATOM
1659
CZ
PHE
269
26.071
18.509
14.679
1.00
25.30


ATOM
1660
C
PHE
269
27.361
23.588
13.917
1.00
22.39


ATOM
1661
O
PHE
269
26.492
23.108
13.910
1.00
22.11


ATOM
1662
N
ARG
270
26.794
24.133
12.841
1.00
24.10


ATOM
1663
CA
ARG
270
27.461
24.132
11.547
1.00
22.53


ATOM
1664
CB
ARG
270
26.638
24.864
10.482
1.00
21.20


ATOM
1665
CG
ARG
270
27.412
25.170
9.196
1.00
17.05


ATOM
1666
CD
ARG
270
26.472
25.476
8.036
1.00
20.10


ATOM
1667
NE
ARG
270
25.772
26.749
8.190
1.00
24.43


ATOM
1668
CZ
ARG
270
24.661
27.094
7.541
1.00
19.92


ATOM
1669
NH1
ARG
270
24.131
28.286
7.754 
1.00
16.84


ATOM
1670
NH2
ARG
270
24.069
26.257
6.695
1.00
18.36


ATOM
1671
C
ARG
270
28.839
24.730
11.667
1.00
21.46


ATOM
1672
O
ARG
270
29.810
24.131
11.230
1.00
25.30


ATOM
1673
N
ARG
271
28.943
25.893
12.286
1.00
24.12


ATOM
1674
CA
ARG
271
30.258
26.509
12.435
1.00
27.33


ATOM
1675
CB
ARG
271
30.155
27.931
13.005
1.00
23.38


ATOM
1676
CG
ARG
271
31.492
28.628
13.101
1.00
19.25


ATOM
1677
CD
ARG
271
31.372
30.006
13.673
1.00
15.09


ATOM
1678
NE
ARG
271
30.776
30.008
15.006
1.00
23.57


ATOM
1679
CZ
ARG
271
29.518
30.367
15.281
1.00
24.60


ATOM
1680
NH1
ARG
271
28.683
30.753
14.326
1.00
23.54


ATOM
1681
NH2
ARG
271
29.095
30.371
16.531
1.00
27.57


ATOM
1682
C
ARG
271
31.177
25.654
13.306
1.00
27.87


ATOM
1683
O
ARG
271
32.185
25.115
12.827
1.00
32.35


ATOM
1684
N
GLU
272
30.812
25.516
14.574
1.00
25.58


ATOM
1685
CA
GLU
272
31.603
24.761
15.525
1.00
23.38


ATOM
1686
CB
GLU
272
30.882
24.679
16.864
1.00
21.26


ATOM
1687
CG
GLU
272
30.754
26.023
17.597
1.00
24.09


ATOM
1688
CD
GLU
272
30.583
25.877
19.126
1.00
28.18


ATOM
1689
OE1
GLU
272
30.578
24.731
19.618
1.00
27.43


ATOM
1690
OE2
GLU
272
30.475
26.912
19.826
1.00
22.15


ATOM
1691
C
GLU
272
32.041
23.376
15.044
1.00
24.71


ATOM
1692
O
GLU
272
33.213
23.038
15.171
1.00
29.53


ATOM
1693
N
MET
273
31.152
22.600
14.425
1.00
24.06


ATOM
1694
CA
MET
273
31.550
21.267
13.963
1.00
21.72


ATOM
1695
CB
MET
273
30.346
20.369
13.702
1.00
18.83


ATOM
1696
CG
MET
273
29.513
20.153
14.957
1.00
25.80


ATOM
1697
SD
MET
273
30.469
19.573
16.380
1.00
26.36


ATOM
1698
CE
MET
273
30.020
18.024
16.256
1.00
25.30


ATOM
1699
C
MET
273
32.486
21.291
12.766
1.00
19.58


ATOM
1700
O
MET
273
33.248
20.352
12.542
1.00
22.39


ATOM
1701
N
THR
274
32.444
22.367
12.001
1.00
20.73


ATOM
1702
CA
THR
274
33.326
22.506
10.857
1.00
20.99


ATOM
1703
CB
THR
274
32.921
23.696
9.929
1.00
23.08


ATOM
1704
OG1
THR
274
31.617
23.470
9.369
1.00
16.49


ATOM
1705
CG2
THR
274
33.934
23.635
8.788
1.00
21.44


ATOM
1706
C
THR
274
34.730
22.765
11.395
1.00
23.86


ATOM
1707
O
THR
274
35.666
22.034
11.055
1.00
25.97


ATOM
1708
N
LEU
275
34.869
23.779
12.251
1.00
21.98


ATOM
1709
CA
LEU
275
36.175
24.142
12.813
1.00
20.62


ATOM
1710
CB
LEU
275
36.035
25.349
13.741
1.00
17.97


ATOM
1711
CG
LEU
275
35.412
26.626
13.158
1.00
20.11


ATOM
1712
CD1
LEU
275
35.130
27.603
14.269
1.00
15.23


ATOM
1713
CD2
LEU
275
36.304
27.264
12.143
1.00
15.87


ATOM
1714
C
LEU
275
36.845
22.996
13.564
1.00
21.58


ATOM
1715
O
LEU
275
38.058 
22.839
13.539
1.00
19.28


ATOM
1716
N
THR
276
36.029 
22.168
14.226
1.00
21.92


ATOM
1717
CA
THR
276
36.489
21.067
15.050
1.00
20.54


ATOM
1718
CB
THR
276
35.589
20.941
16.302
1.00
20.03


ATOM
1719
OG1
THR
276
35.488
22.205
16.964
1.00
27.51


ATOM
1720
CG2
THR
276
36.174
19.971
17.264
1.00
27.26


ATOM
1721
C
THR
276
36.545
19.692
14.413
1.00
18.29


ATOM
1722
O
THR
276
37.294 
18.850
14.864
1.00
24.41


ATOM
1723 
N
VAL
277
35.728
19.424
13.411
1.00
18.63


ATOM
1724
CA
VAL
277
35.738
16.103
12.619
1.00
17.30


ATOM
1725
CB
VAL
277
34.433
17.375
13.124
1.00
18.32


ATOM
1726
CG1
VAL
277
34.492
15.951
12.616
1.00
15.85


ATOM
1727
CG2
VAL
277
34.166
17.401
14.605
1.00
13.45


ATOM
1728
C
VAL
277
35.974
18.079
11.313
1.00
24.98


ATOM
1729
O
VAL
277
36.990 
17.559
10.832
1.00
29.29


ATOM
1730
N
LEU
278
35.027
18.619
10.558
1.00
26.28


ATOM
1731
CA
LEU
278
35.135
18.639
9.100
1.00
23.05


ATOM
1732
CB
LEU
278
33.947
19.402
8.480
1.00
19.55


ATOM
1733
CG
LEU
278
32.553
18.888
8.879
1.00
22.14


ATOM
1734
CE1
LEU
278
31.469
19.721
8.211
1.00
21.06


ATOM
1735
CD2
LEU
278
32.375
17.427
8.536
1.00
13.56


ATOM
1736
C
LEU
278
36.473
19.220
8.641
1.00
20.62


ATOM
1737
O
LEU
278
37.100
18.691
7.731
1.00
21.36


ATOM
1738
N
ASP
279
36.932
20.269
9.312
1.00
19.88


ATOM
1739
CA
ASP
279
38.205
20.904
8.965
1.00
22.41


ATOM
1740
CB
ASP
279
38.353
22.254
9.683
1.00
24.41


ATOM
1741
CG
ASP
279
37.817
23.425
8.871
1.00
24.32


ATOM
1742 
OD1
ASP
279
37.241
23.210
7.777
1.00
23.54


ATOM
1743
OD2
ASP
279
38.015
24.575
9.323
1.00
23.55


ATOM
1744
C
ASP
279
39.428
20.016
9.242
1.00
23.05


ATOM
1745
O
ASP
279
40.492
20.198
8.657
1.00
27.31


ATOM
1746
N
LEU
280
39.263
19.032
10.113
1.00
23.67


ATOM
1747
CA
LEU
280
40.345
18.116
10.453
1.00
17.65


ATOM
1748
CB
LEU
280
40.186
17.700
11.908
1.00
12.01


ATOM
1749
CG
LEU
280
41.302
16.835
12.494
1.00
14.79


ATOM
1750
CD1
LEU
280
42.512
17.735
12.874
1.00
14.08


ATOM
1751
CD2
LEU
280
40.761
16.090
13.692
1.00
2.29


ATOM
1752
C
LEU
280
40.324
16.879
9.531
1.00
14.80


ATOM
1753
O
LEU
280
41.348
16.453
9.015
1.00
14.17


ATOM
1754
N
ILE
281
39.136
16.322
9.365
1.00
12.91


ATOM
1755
CA
ILE
281
38.832
15.173
8.533
1.00
13.11


ATOM
1756
CB
ILE
281
37.212
15.034
8.580
1.00
16.92


ATOM
1757
CG2
ILE
281
36.583
15.195
7.244
1.00
12.65


ATOM
1758
CG1
ILE
281
36.890
13.820
9.397
1.00
21.95


ATOM
1759
CD1
ILE
281
27.394
13.892
10.805
1.00
26.67


ATOM
1760
C
ILE
281
39.427
15.268
7.009
1.00
18.88


ATOM
1761
O
ILE
281
39.820
14.243
6.490
1.00
15.78


ATOM
1762
N
VAL
282
39.530
16.494
6.555
1.00
17.36


ATOM
1763
CA
VAL
282
40.089
16.771
5.209
1.00
14.13


ATOM
1764
CB
VAL
282
40.002
18.262
4.876
1.00
14.53


ATOM
1765
CG1
VAL
282
40.212
18.503
3.416
1.00
14.65


ATOM
1766
CG2
VAL
282
38.751
18.844
5.403
1.00
18.25


ATOM
1767
C
VAL
282
41.598
16.479
5.106
1.00
17.65


ATOM
1768
O
VAL
282
42.124
16.243
4.014
1.00
17.42


ATOM
1769
N
LEU
283
42.304
16.627
6.221
1.00
18.73


ATOM
1770
CA
LEU
283
43.745
16.415
6.261
1.00
16.39


ATOM
1771
CB 
LEU
283
44.326
17.141
7.461
1.00
14.57


ATOM
1772
CG 
LEU
283
44.022
18.624
7.450
1.00
13.01


ATOM
1773
CD1
LEU
283
44.519
19.279
8.693
1.00
12.84


ATOM
1774
CD2
LEU
283
44.674
19.230
6.256
1.00
16.22


ATOM
1775
C
LEU
283
44.170
14.953
6.301
1.00
17.30


ATOM
1776
O
LEU
282
45.294
14.544
5.929
1.00
22.88


ATOM
1777
N
PHE
284
43.277
14.053
6.709
1.00
15.61


ATOM
1778
CA
PHE
284
43.603
12.626
6.804
1.00
15.45


ATOM
1779
CB 
PHE
284
42.359
11.777
7.096
1.00
14.83


ATOM
1780
CG 
PHE
284
41.812
11.897
8.507
1.00
18.52


ATOM
1781
CD1
PHE
284
42.400
12.723
9.451
1.00
14.14


ATOM
1762
CD2
PHE
284
40.646
11.184
8.864
1.00
16.50


ATOM
1783
CE1
PHE
284
41.825
12.837
10.714
1.00
15.64


ATOM
1784
CE2
PHE
294
40.090
11.295
10.092
1.00
7.62


ATOM
1785
CZ
PHE
284
40.670
12.122
11.019
1.00
9.46


ATOM
1786
C
PHE
284
44.310
12.002
5.592
1.00
18.21


ATOM
1787
O
PHE
284
45.276
11.266
5.760
1.00
23.49


ATOM
1788
N
PRO
265
43.851
12.276
4.352
1.00
20.88


ATOM
1789
CD
PRO
285
42.694
13.049
3.863
1.00
15.13


ATOM
1790
CA
PRO
285
44.556
11.644
3.225
1.00
17.86


ATOM
1791
CB
PRO
285
43.763
12.122
2.008
1.00
14.52


ATOM
1792
CG
PRO
285
42.390
12.350
2.575
1.00
15.75


ATOM
1793
C
PRO
285
46.052
11.942
3.079
1.00
14.50


ATOM
1794
O
PRO
285
46.769
11.186
2.424
1.00
14.19


ATOM
1795
N
PHE
286
46.534
12.995
3.722
1.00
14.02


ATOM
1796
CA
PHE
286
47.937
13.353
3.602
1.00
11.79


ATOM
1797
CB
PHE
286
48.089
14.849
3.714
1.00
11.85


ATOM
1798
CG
PHE
286
47.175
15.597
2.800
1.00
13.93


ATOM
1799
CD1
PHE
286
47.188
15.346
1.436
1.00
14.94


ATOM
1800
CD2
PHE
286
46.257
16.502
3.302
1.00
11.76


ATOM
1801
CE1
PHE
286
46.281
15.990
0.576
1.00
14.08


ATOM
1802
CE2
PHE
286
45.348
17.150
2.455
1.00
14.35


ATOM
1803
CZ
PHE
286
45.365
16.887
1.089
1.00
13.45


ATOM
1804
C
PHE
286
48.849
12.631
4.571
1.00
16.19


ATOM
1805
O
PHE
286
50.038
12.936
4.670
1.00
21.52


ATOM
1606
N
TYR
287
48.291
11.685
5.315
1.00
19.21


ATOM
1807
CA
TYR
287
49.077
10.892
6.256
1.00
20.55


ATOM
1808
CB
TYR
287
48.225
10.397
7.441
1.00
19.17


ATOM
1809
CG
TYR
287
47.739
11.484
8.362
1.00
16.07


ATOM
1810
CD1 
TYR
287
48.456
12.671
8.498
1.00
20.52


ATOM
1811
CE1 
TYR
287
48.005
13.696
9.351
1.00
24.03


ATOM
1812
CD2
TYR
287
46.560
11.335
9.097
1.00
15.61


ATOM
1813
CE2
TYR
287
46.101
12.339
9.943
1.00
16.01


ATOM
1814
CZ
TYR
287
46.820
13.517
10.064
1.00
20.29


ATOM
1815
OH
TYR
287
46.359
14.558
10.833
1.00
21.44


ATOM
1816
C
TYR
287
49.579
9.699
5.457
1.00
21.38


ATOM
1817
O
TYR
287
50.471
8.979
5.898
1.00
23.27


ATOM
1818
N
ASP
288
48.971
9.469
4.298
1.00
17.30


ATOM
1819
CA
ASP
288
49.378
8.368
3.430
1.00
17.56


ATOM
1820
CB
ASP
288
48.270
8.102
2.397
1.00
17.03


ATOM
1821
CG
ASP
288
48.601
6.972
1.427
1.00
19.23


ATOM
1822
OD1 
ASP
288
47.665
6.510
0.764
1.00
16.04


ATOM
1823
OD2 
ASP
288
49.766
6.541
1.309
1.00
19.93


ATOM
1824 
C
ASP
288
50.666
8.884
2.774
1.00 
17.17


ATOM
1825
O
ASP
288
50.652
9.342
1.634
1.00
15.73


ATOM
1826
N
ILE
289
51.788
8.743
3.479
1.00
18.54


ATOM
1827
CA
ILE
289
53.066
9.246
3.001
1.00
18.37


ATOM
1828
CB
ILE
289
54.042
9.459
4.194
1.00
19.04


ATOM
1829
CG2
ILE
289
53.428
10.472
5.175
1.00
19.10


ATOM
1830
CG1
ILE
289
54.324
8.143
4.926
1.00
12.09


ATOM
1831
CD1
ILE
289
55.331
7.259
4.239
1.00
11.61


ATOM
1832
C
ILE
289
53.721
8.564
1.782
1.00
21.85


ATOM
1833
O
ILE
289
54.834
8.930
1.363
1.00
23.95


ATOM
1834
N
ARG
290
53.037
7.567
1.224
1.00
19.57


ATOM
1835
CA
ARG
290
53.514
6.884
0.029
1.00
18.74


ATOM
1836
CB
ARG
290
53.182
5.394
0.051
1.00
17.14


ATOM
1837
CG
ARG
290
54.014
4.639
1.055
1.00
23.48


ATOM
1838
CD
ARG
290
53.876
3.149
0.876
1.00
34.60


ATOM
1839
NE
ARG
290
54.451
2.353
1.971
1.00
46.59


ATOM
1840
CE
ARG
290
55.735
2.347
2.345
1.00
47.76


ATOM
1841
NH1
ARG
290
56.626
3.117
1.723
1.00
51.55


ATOM
1842
NH2
ARG
290
56.149
1.501
3.292
1.00
45.76


ATOM
1843
C
ARG
290
52.847
7.567
−1.151
1.00
16.63


ATOM
1844
O
ARG
290
53.488
7.832
2.144
1.00
19.86


ATOM
1845
N
LEU
291
51.578
7.914
−1.011
1.00
13.74


ATOM
1846
CA
LEU
291
50.849
8.592
−2.084
1.00
15.52


ATOM
1847
CB
LEU
291
49.355
8.420
−1.874
1.00
13.32


ATOM
1848
CG
LEU
291
48.362
8.707
−2.984
1.00
16.72


ATOM
1849
CD1
LEU
291
48.440
7.651
−4.049
1.00
17.92


ATOM
1850
CD2
LEU
291
47.010
8.654
−2.355
1.00
17.47


ATOM
1851
C
LEU
291
51.231
10.077
−2.104
1.00
18.05


ATOM
1852
O
LEU
291
51.168
10.722
−3.145
1.00
20.46


ATOM
1853
N
TYR
292
51.564
10.638
−0.941
1.00
16.65


ATOM
1854
CA
TYR
292
51.995
12.028
−0.857
1.00
15.57


ATOM
1855
CE
TYR
292
50.999
12.900
−0.118
1.00
13.30


ATOM
1856
CG
TYR
292
49.652
13.041
−0.770
1.00
17.69


ATOM
1857
CD1 
TYR
292
48.642
12.118
−0.519
1.00
14.60


ATOM
1858
CE1 
TYR
292
47.386
12.269
−1.084
1.00
11.38


ATOM
1859
CD2 
TYR
292
49.372
14.125
−1.614
1.00
14.26


ATOM
1860
CE2
TYR
292
48.125
14.279
−2.186
1.00
9.45


ATOM
1861
CZ
TYR
292
47.136
13.349
−1.913
1.00
13.74


ATOM
1862
OH
TYR
292
45.880
13.498
−2.464
1.00
19.44


ATOM
1863
C
TYR
292
53.248
12.005
−0.040
1.00
17.77


ATOM
1864
O
TYR
292
53.188
12.265
1.140
1.00
21.18


ATOM
1865
N
SER
293
54.388
11.715
−0.652
1.00
17.12


ATOM
1866
CA
SER
293
55.630
11.650
0.098
1.00
18.41


ATOM
1867
CB
SER
293
56.527
10.586
−0.502
1.00
22.40


ATOM
1868
OG
SER
293
57.151
11.100
−1.661
1.00
17.65


ATOM
1869
C
SER
293
56.437
12.927
0.177
1.00
20.90


ATOM
1870
O
SER
293
57.334
13.013
1.008
1.00
27.08


ATOM
1871
N
LYS
294
56.134
13.911
−0.672
1.00
21.04


ATOM
1872
CA
LYS
294
56.899
15.174
−0.741
1.00
21.20


ATOM
1873
CB
LYS
294
56.888
15.687
−2.188
1.00
24.69


ATOM
1874
CG
LYS
294
57.667
14.826
−3.155
1.00
30.89


ATOM
1875
CD
LYS
294
57.400
15.182
−4.601
1.00
36.85


ATOM
1876
CE
LYS
294
56.381
14.457
−5.546
1.00
40.74


ATOM
1877
NZ
LYS
294
58.259
12.949
−5.574
1.00
49.08


ATOM
1878
C
LYS
294
56.464
16.329
0.148
1.00
21.21


ATOM
1879
O
LYS
294
57.117
17.375
0.194
1.00
24.04


ATOM
1880
N
GLY
295
55.374
16.150
0.863
1.00
19.05


ATOM
1881
CA
GLY
295
54.852
17.243
1.660
1.00
23.45


ATOM
1882
C
GLY
295
53.652
17.716
0.870
1.00
19.08


ATOM
1883
O
GLY
295
53.586
17.408
−0.305
1.00
25.31


ATOM
1884
N
VAL
296
52.691
18.410
1.466
1.00
16.95


ATOM
1885
CA
VAL
296
51.539
18.844
0.690
1.00
17.59


ATOM
1886
CB
VAL
296
50.299
17.958
0.980
1.00
15.37


ATOM
1887
CG1
VAL
296
49.139
18.372
0.110
1.00
11.50


ATOM
1888
CG2
VAL
296
50.612
16.502
0.708
1.00
18.57


ATOM
1889
C
VAL
296
51.182
20.302
0.955
1.00
20.48


ATOM
.1890
0
VAL
296
51.102
20.722
2.108
1.00
27.73


ATOM
1891
N
LYS
297
50.985
21.077
−0.105
1.00
19.95


ATOM
1692
CA
LYS
297
50.604
22.472
0.027
1.00
19.51


ATOM
1893
CB
LYS
297
51.444
23.358
−0.883
1.00
21.95


ATOM
1.894
CG
LYS
297
51.011
24.799
−0.891
1.00
23.14


ATOM
1895
Cr
LYS
297
51.814
25.617
−1.892
1.00
24.37


ATOM
1896
CE
LYS
297
51.247
27.021
−2.068
1.00
24.23


ATOM
1897
NZ
LYS
297
49.881
27.038
−2.664
1.00
23.46


ATOM
1898
C
LYS
297
49.143
22.532
−0.371
1.00
20.96


ATOM
1899
O
LYS
297
48.816
22.330
−1.533
1.00
21.98


ATOM
1900
N
THR
298
48.268
22.633
0.626
1.00
21.00


ATOM
1901
CA
THR
298
46.839
22.728
0.400
1.00
22.17


ATOM
1902
CB
THR
298
46.094
21.394
0.679
1.00
24.36


ATOM
1903
CG1
THR
298
44.705
21.551
0.328
1.00
21.16


ATOM
1904
CG2
THR
298
46.242
20.949
2.132
1.00
13.02


ATOM
1905
C
THR
298
46.203
23.850
1.210
1.00
21.58


ATOM
1906
O
THR
298
46.881
24.562
1.936
1.00
22.42


ATOM 
1907
N
GLU
299
44.897
24.020
1.069
1.00
20.01


ATOM
1908
CA
GLU
299
44.202
25.069
1.790
1.00
23.19


ATOM
1909
CB
GLU
299
44.394
26.388
1.028
1.00
21.52


ATOM
1910
CG
GLU
299
44.111
26.241
−0.457
1.00
24.08


ATOM
1911
CD
GLU
299
44.281
27.511
−1.246
1.00
21.25


ATOM
1912
OE1
GLU
299
43.347
27.904
−1.952
1.00
23.36


ATOM
1913
OE2
GLU
299
45.363
28.099
−1.199
1.00
25.32


ATOM
1914
C
GLU
299
42.709
24.689
1.942
1.00
22.52


ATOM
1915
O
GLU
299
42.226
23.799
1.218
1.00
21.89


ATOM
1916
N
LEU
300
42.031
25.288
2.935
1.00
18.80


ATOM
1917
CA
LEU
300
40.599
25.057
3.208
1.00
17.80


ATOM
1918
CB
LEU
300
40.346
24.957
4.716
1.00
18.20


ATOM
1919
CG
LEU
300
41.052
23.781
5.409
1.00
18.16


ATOM
1920
CD1
LEU
300
41.281
24.050
6.878
1.00
22.65


ATOM
1921
CD2
LEU
300
40.232
22.548
5.238
1.00
21.52


ATOM
1922
C
LEU
300
39.835
26.246
2.626
1.00
15.99


ATOM
1923
O
LEU
300
40.070
27.384
3.019
1.00
15.87


ATOM
1924
N
THR
301
38.920
25.988
1.691
1.00
16.43


ATOM
1925
CA
THR
301
38.196
27.078
1.039
1.00
16.67


ATOM
1926
CB
THR
301
38.204
26.860
−0.486
1.00
15.99


ATOM
1927
OG1
THR
301
37.397
25.725
−0.795
1.00
17.35


ATOM
1928
CG2
THR
301
39.629
26.604
−1.001
1.00
12.86


ATOM
1929
C
THR
301
36.750
27.381
1.451
1.00
16.97


ATOM
1930
O
THR
301
36.115
28.216
0.844
1.00
20.08


ATOM
1931
N
ARG
302
36.239
26.775
2.509
1.00
20.61


ATOM
1932
CA
ARG
302
34.849
27.007
2.891
1.00
21.32


ATOM
1933
CB
ARG
302
34.287
25.864
3.750
1.00
18.48


ATOM
1934
CG
ARG
302
34.722
25.893
5.198
1.00
14.88


ATOM
1935
CD
ARG
302
36.172
25.671
5.287
1.00
9.35


ATOM
1936
NE
ARG
302
36.696
25.844
6.621
1.00
20.42


ATOM
1937
CZ
ARG
302
37.108
27.008
7.107
1.00
22.97


ATOM
1938
NH1
ARG
302
37.594
27.070
8.146
1.00
22.13


ATOM
1939
NH2
ARG
302
36.999
28.107
6.368
1.00
17.69


ATOM
1940
C
ARG
302
34.591
28.299
3.621
1.00
20.20


ATOM
1941
O
ARG
302
35.471
28.855
4.271
1.00
17.57


ATOM
1942
N
ASP
303
33.346
28.737
3.495
1.00
25.15


ATOM
1943
CA
ASP
303
32.809
29.930
4.140
1.00
26.98


ATOM
1944
CB
ASP
303
31.470
30.313
3.515
1.00
26.18


ATOM
1945
CG
ASP 
303
31.601
30.933
2.177
1.00
29.18


ATOM
1946
OD1
ASP
303
32.703
31.375
1.800
1.00
37.69


ATOM
1947
OD2
ASP 
303
30.568
31.017
1.497
1.00
35.54


ATOM
1948
C
ASP
303
32.469
29.534
5.571
1.00
28.25


ATOM
1949
O
ASP
303
31.989
28.421
5.828
1.00
31.50


ATOM
1950
N
ILE
304
32.606
30.486
6.475
1.00
26.71


ATOM
1951
CA
ILE
304
32.283
30.267
7.862
1.00
25.31


ATOM
1952
CB
ILE
304
33.569
30.156
8.723
1.00
22.72


ATOM
1953
CG2
ILE
304
33.322
30.558
10.144
1.00
20.05


ATOM
1954
CG1
ILE
304
34.034
28.714
8.723
1.00
19.75


ATOM
1955
CD1
ILE
304
32.954
27.806
9.196
1.00
14.92


ATOM
1956
C
ILE
304
31.423
31.448
8.250
1.00
26.33


ATOM
1957
O
ILE
304
31.748
32.595
7.922
1.00
25.80


ATOM
1958
N
PHE 305
30.268
31.152
8.835
1.00
28.50



ATOM
1959
CA
PHE
305
29.344
32.188
9.293
1.00
31.16


ATOM
1960
CB
PHE
305
27.912
31.852
8.877
1.00
36.40


ATOM
1961
CG
PHE
305
27.662
32.026
7.432
1.00
42.07


ATOM
1962
CD1
PHE 
305
27.899
30.985
6.549
1.00
46.03


ATOM
1963
CD2
PHE
305
27.261
33.254
6.938
1.00
49.89


ATOM
1964
CE1
PHE 
305
27.752 
31.156 
5.185
1.00
49.49


ATOM
1965
CE2
PHE
305
27.106
33.446
5.571
1.00
54.89


ATOM
1966
CZ
PHE 
305
27.357
32.389
4.689
1.00
54.32


ATOM
1967
C
PHE
305
29.375
32.382
10.814
1.00
29.64


ATOM
1968
O
PHE
305
28.992
31.475
11.567
1.00
25.99


ATOM
1969
N
THR
306
29.882
33.533
11.261
1.00
28.12


ATOM
1970
CA
THR
306
29.873
33.837
12.679
1.00
28.81


ATOM
1971
CB
THR 
306
30.779
35.048
13.049
1.00
26.16


ATOM
1972
OG1
THR
306
30.624
36.078
12.082
1.00
27.19


ATOM
1973
CG2
THR
306
32.246
34.647
13.127
1.00
20.81


ATOM
1974
C
THR
306
28.387
34.136
12.965
1.00
30.50


ATOM
1975
O
THR
306
27.599
34.289
12.034
1.00
32.53


ATOM
1976
N
ASP
307
27.981
34.164
14.229
1.00
30.85


ATOM
1977
CA
ASP
307
26.582
34.411
14.551
1.00
28.56


ATOM
1978
CB
ASP
307
26.331
34.154
16.028
1.00
27.80


ATOM
1979
CG
ASP
307
26.639
32.741
16.427
1.00
25.34


ATOM
1980
OD1
ASP
307
26.394
31.814
15.621
1.00
27.45


ATOM
1981
OD2
ASP
307
27.126
32.565
17.556
1.00
26.95


ATOM
1982 
C
ASP
307
26.203
35.830
14.234
1.00
29.47


ATOM
1983
O
ASP
307
27.060
36.690
14.098
1.00
32.38


ATOM
1984
N
PRO
308
24.905
36.104
14.119
1.00
32.45


ATOM
1985
CD
PRO
308
23.768
35.163
14.163
1.00
31.35


ATOM
1986
CA
PRO
308
24.467
37.472
13.815
1.00
34.04


ATOM
1987
CB
PRO
308
22.958
37.360
13.956
1.00
34.15


ATOM
1988
CG
PRO
308
22.694
35.936
13.472
1.00
32.65


ATOM
1989
C
PRO
305
25.098
38.483
14.800
1.00
37.93


ATOM
1990
O
PRO
308
25.202
38.187
15.998
1.00
37.44


ATOM
1991
N
ILE
309
25.503
39.659
14.286
1.00
40.34


ATOM
1992
CA
ILE
309
26.182
40.696
15.087
1.00
43.93


ATOM
1993
CB 
ILE
309
26.369
42.034
14.319
1.00
48.28


ATOM
1994
CG2
ILE
309
26.862
43.148
15.252
1.00
51.65


ATOM
1995
CG1
ILE
309
27.437
41.892
13.240
1.00
49.09


ATOM
1996
CD1
ILE
309
27.842
43.242
12.649
1.00
46.27


ATOM
1997
C
ILE
309
25.651
40.995
16.506
1.00
44.62


ATOM
1998
O
ILE
309
26.432
41.296
17.431
1.00
41.13


ATOM
1999
N
PHE
310
24.341
41.003
16.675
1.00
42.38


ATOM
2000
CA 
PHE
110
23.843
41.236
18.003
1.00
41.16


ATOM
2001
CB
PHE
310
23.491
42.705
18.235
1.00
44.88


ATOM
2002
CO
PHE
310
22.411
43.235
17.351
1.00
44.58


ATOM
2003
CD1
PHE
310
21.077
43.166
17.747
1.00
44.20


ATOM
2004
CD2
PHE
310
22.724
43.860
16.159
1.00
38.66


ATOM
2005
CE1
PHE
310
20.076
43.717
16.967
1.00
42.71


ATOM
2006
CE2
PHE
310
21.735
44.406
15.386
1.00
41.33


ATOM
2007
C2
PHE
310
20.404
44.337
15.789
1.00
42.16


ATOM
2008
C
PHE
310
22.717
40.301
18.347
1.00
44.75


ATOM
2009
O
PHE
310
21.985
39.837
17.402
1.00
43.78


ATOM
2010
N
SER
311
22.633
39.981
19.627
1.00
51.28


ATOM
2011
CA
SER
311
21.629
39.064
20.151
1.00
56.76


ATOM
2012
CB
SER
311
22.166
38.462
21.440
1.00
58.74


ATOM
2013
OG
SER
311
23.083
39.374
22.031
1.00
61.15


ATOM
2014
C
SER
311
20.271
39.696
20.410
1.00
57.21


ATOM
2015
O
SER
311
20.125
40.505
21.328
1.00
59.60


ATOM
2016
N
LEU
312
19.275
39.303
19.625
1.00
57.51


ATOM
2017
CA
LEU
312
17.921
39.828
19.779
1.00
58.49


ATOM
2018
CD 
LEU
312
17.065
39.425
18.573
1.00
53.40


ATOM
2019
CG
LEU
312
17.575
39.521
17.136
1.00
49.68


ATOM
2020
CD1
LEU
312
16.401
39.249
16.208
1.00
45.27


ATOM
2021
CD2
LEU
312
18.174
40.885
16.843
1.00
49.90


ATOM
2022
C
LEU
312
17.316
39.231
21.057
1.00
60.36


ATOM
2023
O
LEU
312
16.569
38.269
21.001
1.00
64.66


ATOM
2024
N
ASN
313
17.651
39.786
22.210
1.00
60.93


ATOM
2025
CA
ASN
313
17.137
39.258
23.471
1.00
63.91


ATOM
2026
CB
ASN
313
17.737
40.037
24.667
1.00
71.17


ATOM
2027
CG
ASN
313
17.813
41.566
24.434
1.00
75.38


ATOM
2028
OD1
ASN
313
16.997
42.160
23.713
1.00
78.86


ATOM
2029
ND2
ASN
313
18.789
42.199
25.067
1.00
76.26


ATOM
2030
C
ASN
313
15.601
39.188
23.555
1.00
62.62


ATOM
2031
O
ASN
313
14.989
38.133
23.364
1.00
59.81


ATOM
2032
N
THR
314
14.990
40.330
23.839
1.00
61.63


ATOM
2033
CA
THR
314
13.549
40.458
23.948
1.00
57.86


ATOM
2034
CB
THR
314
13.217
41.790
24.674
1.00
58.51


ATOM
2035
OG1
THR
314
13.881
41.819
25.946
1.00
58.32


ATOM
2036
CG2
THR
314
11.724
41.947
24.888
1.00
59.87


ATOM
2037
C
THR
314
12.970
40.457
22.523
1.00
55.92


ATOM
2038
O
THR
314
11.757
40.260
22.327
1.00
55.62


ATOM
2039
N
LEU
315
13.856
40.624
21.537
1.00
52.11


ATOM
2040
CA
LEU
315
13.486
40.683
20.122
1.00
49.01


ATOM
2041
CB
LEU
315
14.320
41.757
19.404
1.00
50.14


ATOM
2042
CG
LEU
315
14.328
43.217
19.874
1.00
50.23


ATOM
2043
CD1
LEU
315
14.815
44.078
18.718
1.00
51.73


ATOM
2044
CD2
LEU
315
12.933
43.680
20.328
1.00
47.63


ATOM
2045
C
LEU
315
13.621
39.375
19.347
1.00
47.16


ATOM
2046
O
LEU
315
13.292
39.312
18.157
1.00
43.27


ATOM
2047
N
GLN
316
14.097
38.340
20.023
1.00
47.36


ATOM
2048
CA
GLN
316
14.311
37.036
19.414
1.00
48.53


ATOM
2049
CB
GLN
316
14.411
35.977
20.510
1.00
51.64


ATOM
2050
CG
GLN
316
15.051
34.671
20.073
1.00
57.31


ATOM
2051
CD
GLN
316
16.565
34.769
19.894
1.00
60.35


ATOM
2052
OE1
GLN
316
17.108
35.810
19.506
1.00
60.96


ATOM
2053
NE2
GLN
316
17.254
33.665
20.169
1.00
63.62


ATOM
2054
C
GLN
316
13.200
36.663
18.451
1.00
49.57


ATOM
2055
O
GLN
316
13.454
36.241
17.320
1.00
50.18


ATOM
2056
N
GLU
317
11.968
36.870
18.901
1.00
48.85


ATOM
2057
CA
GLU
317
10.775
36.544
18.126
1.00
52.71


ATOM
2058
CB
GLU
317
9.501
36.796
18.953
1.00
60.20


ATOM
2059
CG
GLU
317
9.493
36.204
20.377
1.00
70.71


ATOM
2060
CD
GLU
317
9.881
37.227
21.456
1.00
76.72


ATOM
2061
OE1
GLU
317
9.273
38.333
21.480
1.00
77.12


ATOM
2062
OE2
GLU
317
10.787
36.920
22.274
1.00
77.99


ATOM
2063
C
GLU
317
10.657
37.293
16.799
1.00
48.71


ATOM
2064
O
GLU
317
10.071
36.780
15.844
1.00
48.70


ATOM
2065
N
TYR
318
11.214
38.494
16.739
1.00
43.49


ATOM
2066
CA
TYR
318
11.129
39.300
15.538
1.00
39.92


ATOM
2067
CB
TYR
318
10.999
40.761
15.918
1.00
42.45


ATOM
2068
CG
TYR
318
9.803
40.971
16.782
1.00
42.68


ATOM
2069
CD1
TYR
318
9.946
41.197
18.144
1.00
40.60


ATOM
2070
CE1
TYR
318
8.849
41.304
18.969
1.00
40.01


ATOM
2071
CE2
TYR
318
8.526
40.860
16.260
1.00
38.85


ATOM
2072
CE2
TYR
318
7.424
40.969
17.078
1.00
40.89


ATOM
2073
CZ
TYR
318
7.593
41.189
18.437
1.00
39.14


ATOM
2074
OH
TYR
318
6.503
41.297
19.273
1.00
45.54


ATOM
2075
C
TYR
318
12.233
39.130
14.522
1.00
37.64


ATOM
2076
O
TYR
318
12.303
39.886
13.561
1.00
38.76


ATOM
2077
N
GLY
319
13.093
38.141
14.703
1.00
35.33


ATOM
2078
CA
GLY
319
14.154
37.962
13.733
1.00
31.25


ATOM
2079
C
GLY
319
13.662
37.273
12.475
1.00
30.50


ATOM
2080
O
GLY
319
12.575
36.689
12.503
1.00
32.90


ATOM
2081
N
PRO
320
14.385
37.395
11.344
1.00
26.91


ATOM
2082
CD
PRO
320
15.499
38.333
11.174
1.00
23.64


ATOM
2083
CA
PRO
320
14.061
36.776
10.053
1.00
29.07


ATOM
2084
CD
PRO
320
15.295
37.106
9.210
1.00
29.08


ATOM
2085
CG
PRO
320
16.336
37.590
10.207
1.00
28.14


ATOM
2086
C
PRO
320
13.880
35.251
10.152
1.00
30.61


ATOM
2087
O
PRO
320
14.650
34.591
10.831
1.00
32.60


ATOM
2088
N
THR
321
12.899
34.685
9.451
1.00
32.83


ATOM
2089
CA
THR
321
12.676
33.245
9.523
1.00
36.83


ATOM
2090
CB
THR
321
11.362
32.782
8.776
1.00
41.13


ATOM
2091
CG1
THR
321
11.482
12.904
7.346
1.00
35.95


ATOM
2092
CG2
THR
321
10.177
33.597
9.267
1.00
40.68


ATOM
2093
C
THR
321
13.871
32.438
9.041
1.00
37.20


ATOM
2094
O
THR
321
14.789
32.985
8.429
1.00
41.10


ATOM
2095
N
PHE
322
13.873
31.149
9.369
1.00
38.20


ATOM
2096
CA
PHE
322
14.941
30.216
8.993
1.00
36.64


ATOM
2097
CB
PHE
322
14.548
28.794
9.455
1.00
35.09


ATOM
2098
CG
PHE
322
15.669
27.776
9.400
1.00
37.60


ATOM
2099
CD1
PHE
322
16.356
27.416
10.554
1.00
36.41


ATOM
2100
CD2
PHE
322
16.016
27.157
8.204
1.00
36.13


ATOM
2101
CE1
PHE
322
17.359
26.466
10.505
1.00
32.41


ATOM
2102 
CE2
PHE
322
11.012
26.216
8.159
1.00
25.56


ATOM
2103
CZ
PHE
322
17.682
25.872
9.307
1.00
28.83


ATOM
2104
C
PHE
322
15.139
30.260
7.470
1.00
34.25


ATOM
2105
O
PHE
322
16.191
30.671
6.987
1.00
26.49


ATOM
2106
N
LEU
323
14.081
29.907
6.739
1.00
36.36


ATOM
2107
CA
LEU
323
14.078
29.876
5.281
1.00
39.50


ATOM
2108
CB
LEU
323
12.713
29.427
4.739
1.00
46.13


ATOM
2109
CG
LEU
323
12.323
27.951
4.927
1.00
50.61


ATOM
2110
CD1
LEU
323
10.873
27.714
4.506
1.00
52.63


ATOM
2111
CD2
LEU
323
13.267
27.041
4.131
1.00
52.44


ATOM
2112
C
LEU
323
14.486
31.183
4.627
1.00
41.16


ATOM
2113
O
LEU
323
15.230
31.174
3.651
1.00
45.33


ATOM
2114
N
SER
324
14.006
32.310
5.132
1.00
40.97


ATOM
2115
CA
SER
324
14.400
33.583
4.545
1.00
43.00


ATOM
2116
CB
SER
324
13.565
34.730
5.111
1.00
47.79


ATOM
2117
OG
SER
324
13.504
34.673
6.527
1.00
60.21


ATOM
2118
C
SER
324
15.892
33.840
4.774
1.00
40.32


ATOM
2119
O
SER
324
16.524
34.581
4.031
1.00
40.93


ATOM
2120
N
ILE
325
16.457
33.237
5.803
1.00
38.03


ATOM
2121
CA
ILE
325
17.863
33.420
6.060
1.00
35.42


ATOM
2122
CG
ILE
325
18.206
33.218
7.502
1.00
32.99


ATOM
2123
CG2
ILE
325
19.698
33.445
7.696
1.00
32.52


ATOM
2124
CG1
ILE
325
17.402
34.213
8.338
1.00
29.14


ATOM
2125
CD1
ILE
325
17.483
33.959
9.785
1.00
28.48


ATOM
2126
C
ILE
325
18.647
32.464
5.204
1.00
36.75


ATOM
2127
O
ILE
325
19.540
32.893
4.493
1.00
35.77


ATOM
2128
N
GLU
326
18.280
31.181
5.228
1.00
41.70


ATOM
2129
CA
GLU
326
18.958
30.159
4.420
1.00
45.37


ATOM
2130
CB
GUI
326
18.567 28.733
4.849
1.00
44.39



ATOM
2131
CG
GLU
326
19.363
28.140
6.032
1.00
46.61


ATOM
2132
CD
GLU
326
20.865
27.938
5.771
1.00
46.09


ATOM
2133
OE1
GLU
326
21.672
28.753
6.258
1.00
47.88


ATOM
2134
OE2
GLU
326
21.253
26.941
5.126
1.00
50.34


ATOM
2135
C
GLU
326
18.733
30.312
2.908
1.00
47.91


ATOM
2136
O
GLU
326
19.515
29.795
2.111
1.00
52.83


ATOM
2137
N
ASN
327
17.667
30.992
2.503
1.00
49.53


ATOM
2138
CA
ASN
327
17.392
31.186
1.077
1.00
50.26


ATOM
2139
CB
ASN
327
15.883
31.067
0.785
1.00
57.24


ATOM
2140
CG
ASN
327
15.348
29.639
0.923
1.00
63.35


ATOM
2141
OD1
ASN
327
14.362
29.271
0.272
1.00
65.72


ATOM
2142
OD2
ASN
327
15.973
28.838
1.787
1.00
66.61


ATOM
2143
C
ASN
327
17.885
32.557
0.602
1.00
49.12


ATOM
2144
O
ASN
327
17.732
32.910
−0.566
1.00
48.41


ATOM
2145
N
SER
328
18.460
33.336
1.513
1.00
48.24


ATOM
2146
CA
SER
320
18.940
34.666
1.177
1.00
44.37


ATOM
2147
CB
SER
328
16.354
35.682
2.141
1.00
43.90


ATOM
2148
CG
SER
328
18.337
36.973
1.573
1.00
53.23


ATOM
2149
C
SER
328
20.448
34.713
1.234
1.00
42.82


ATOM
2150
O
SER
328
21.068
35.599
0.662
1.00
44.52


ATOM
2151
N
ILE
329
21.043
33.789
1.973
1.00
41.88


ATOM
2152
CA
ILE
329
22.489
33.739
2.053
1.00
43.60


ATOM
2153
CB
ILE
329
23.002
32.593
2.976
1.00
47.00


ATOM
2154
CG2
ILE
329
24.519
32.637
3.053
1.00
51.01


ATOM
2155
CG1
ILE
329
22.439
32.700
4.395
1.00
45.80


ATOM
2156
CD1
ILE
329
23.249
33.560
5.348
1.00
51.95


ATOM
2157
C
ILE
329
22.993
33.464
0.632
1.00
44.62


ATOM
2158
O
ILE
329
22.281
32.911
−0.215
1.00 
42.08


ATOM
2159
N
ARG
330
24.244
33.838
0.409
1.00
47.30


ATOM
2160
CA
ARG
330
24.963
33.693
−0.851
1.00
46.81


ATOM
2161
CB
ARG
330
26.279
34.416
−0.638
1.00
45.98


ATOM
2162
CG
ARG
330
27.046 
34.848
−1.827
1.00
44.32


ATOM
2163
CD
ARG
330
28.355
35.373
−1.277
1.00
42.48


ATOM
2164
NE
ARG
330
29.270
35.765
−2.322
1.00
38.20


ATOM
2165
CZ
ARG
330
30.584
35.790
−2.188
1.00
34.54


ATOM
2166
NH1
ARG
330
31.303
36.170
−3.213
1.00
39.28


ATOM
2167
NH2
ARG
330
31.172
35.436
−1.055
1.00
32.79


ATOM
2168
C
ARG
330
25.214
32.203
−1.154
1.00
47.48


ATOM
2169
O
ARG
330
25.815
31.492
−0.345
1.00
49.75


ATOM
2170
N
LYS
331
24.788
31.735
−2.323
1.00
44.85


ATOM
2171
CA
LYS
331
24.965
30.321
−2.677
1.00
45.45


ATOM
2172
CB
LYS
331
23.947
29.905
−3.795
1.00
47.94


ATOM
2173
CG
LYS
331
23.989
30.723
−5.023
1.00
58.90


ATOM
2174
CD
LYS
331
22.634
30.357
−5.938
1.00
66.64


ATOM
2175
CE
LYS
331
22.853
31.194
−7.215
1.00
71.89


ATOM
2176
NE
LYS
331
21.564
31.088
−7.969
1.00
75.69


ATOM
2177
C
LYS
331
26.413
29.994
−3.086
1.00
39.16


ATOM
2178
O
LYS
331
27.229
30.912
−3.208
1.00
35.42


ATOM
2179
N
PRO
332
26.759
28.687
−3.243
1.00
36.88


ATOM
2180
CD
PRO
332
25.907
27.510
−2.988
1.00
34.11


ATOM
2181
CA
PRO
332
28.113
28.249
−3.627
1.00
35.07


ATOM
2.182
CH
PRO
332
27.952
26.732
−3.834
1.00
31.43


ATOM
2183
CG
PRO
332
26.465
26.521
−3.945
1.00
34.71


ATOM
2184
C
PRO
332
28.695
28.993
−4.237
1.00
33.27


ATOM
2185
O
PRO
332
28.069
29.092
−5.891
1.00
32.47


ATOM
2186
N
HIS
333
29.927
29.464
4.675
1.00
31.69


ATOM
2187
CA
HIS
333
30.592
30.283
−5.677
1.00
29.36


ATOM
2188
CB
HIS
333
30.345
31.755
−5.284
1.00
29.61


ATOM
2189
CG
HIS
333
30.759
32.078
−3.874
1.00
31.85


ATOM
2190
CD2
HIS
333
31.978
32.349
−3.343
1.00
30.11


ATOM
2191
NE1
HIS
333
29.879
32.052
−2.811
1.00
12.89


ATOM
2192
CE1
HIS
333
30.540
32.282
−1.688
1.00
33.67


ATOM
2193
NE2
HIS
333
31.815
32.467
−1.981
1.00
27.12


ATOM
2194
C
HIS
333
32.106
30.062
5.781
1.00
25.03


ATOM
2195
O
HIS
333
32.719
29.414
−4.932
1.00
25.48


ATOM
2196
N
LEU
334
32.706
30.630
−6.817
1.00
23.62


ATOM
2197
CA
LEU
334
34.156
30.561
−6.982
1.00
25.27


ATOM
2198
CB
LEU
334
34.615
31.210
−8.298
1.00
20.89


ATOM
2199
CG
LEU
334
34.198
30.552
−9.612
1.00
21.30


ATOM
2200
CD1
LEU
334
34.810
31.273
−10.609
1.00
16.30


ATOM
2201
CD2
LEU
334
34.625
29.094
−9.573
1.00
19.51


ATOM
2202
C
LEU
334
34.668
31.415
−5.837
1.00
25.83


ATOM
2203
O
LEU
334
34.023 
32.389
−5.461
1.00
27.82


ATOM
2204
N
PHE
335
35.832
31.077
−5.306
1.00
27.75


ATOM
2205
CA
PHE
335
36.413
31.821
−4.195
1.00
24.44


ATOM
2206
CB
PHE
335
37.718
31.140
−3.764
1.00
25.26


ATOM
2207
CG
PHE
335
38.196
31.546 
−2.403
1.00
27.14


ATOM
2208
CD1
PHE
335
37.761 
30.866
−1.269
1.00
27.42


ATOM
2209
CD2
PHE
335
39.077
32.609
−2.249
1.00
29.95


ATOM
2210
CE1
PHE
335
38.191
31.246
−0.002
1.00
31.73


ATOM
2211
CE2
PHE
335
39.514
32.997
−0.983
1.00
31.29


ATOM
2212
CZ 
PHE
335
39.073
32.318
0.141 
1.00
29.70


ATOM
2213
C
PHE
335
36.719
33.250
−4.601
1.00
21.92


ATOM
2214
O
PHE
335
37.287
33.463
−5.653
1.00
23.54


ATOM
2215
N
ASP
336
36.340
34.217
3.772
1.00
21.21


ATOM
2216
CA
ASP
336
38.652
35.623
−4.018
1.00
21.48


ATOM
2217
CB
ASP
336
35.525
36.366
−4.718
1.00
23.79


ATOM
2218
CG
ASP
336
34.172
36.174
−4.082
1.00
23.35


ATOM
2219
OD1
ASP
336
34.038
36.239
−2.844
1.00
22.38


ATOM
2220
OD2
ASP
336
33.228
35.955
−4.868
1.00
31.58


ATOM
2221
C
ASP
336
37.061
35.300 
−2.715
1.00
22.29


ATOM
2222
O
ASP
336
36.904
35.720
−1.661
1.00
25.71


ATOM
2223
N
TYR
337
37.518
37.544
−2.788
1.00
20.76


ATOM
2224
CA
TYR
337
38.037
38.268 
−1.632
1.00
21.98


ATOM
2225
CB
TYR
337
39.538
38.538
−1.877
1.00
17.10


ATOM
2226
CG
TYR
337
40.339
37.311
−2.313
1.00
17.63


ATOM
2227
CD1
TYR
337
40.203
36.764
−3.590
1.00
20.68


ATOM
2228
CE1
TYR
337
40.875
35.572
−3.955
1.00
23.11


ATOM
2229
CD2 
TYR
337
41.178
36.648
−1.415
1.00
23.13


ATOM
2230
CE2
TYR
337
41.854
35.466
−1.766
1.00
23.39


ATOM
2231
CZ
TYR
337
41.094
34.934
−3.030
1.00
24.50


ATOM
2232
OH
TYR
337
42.330
33.758
−3.332
1.00
26.47


ATOM
2233
C
TYR
337
37.305
39.586
−1.400
1.00
22.36


ATOM
2234
O
TYR
337
36.807
40.175
−2.333
1.00
24.56


ATOM
2235
N
LEU
338
37.283
40.079
−0.170
1.00
26.34


ATOM
2236
CA
LEU
338
36.590
41.342
0.121
1.00
29.06


ATOM
2237
CB
LEU
338
36.422
41.557
1.642
1.00
28.21


ATOM
2238
CG
LEU
338
35.501
42.690
2.150
1.00
25.11


ATOM
2239
CD1
LEU
338
34.056
42.386
1.828
1.00
24.92


ATOM
2240
CD2
LEU
338
35.645
42.872
3.652
1.00
24.77


ATOM
2241
C
LEU
338
37.318
42.542
−0.480
1.00
29.54


ATOM
2242
O
LEU
338
38.543
42.674
−0.332
1.00
32.83


ATOM
2243
N
GLN
339
36.562
43.389
−1.178
1.00
28.15


ATOM
2244
CA
GLN
339
37.101
44.605
−1.793
1.00
31.21


ATOM
2245
CB
GLN
339
16.617
44.766
−3.242
1.00
40.03


ATOM
2246
CG
GLN
339
37.561
44.240
−4.307
1.00
49.91


ATOM
2247
CD
GLN
339
38.935
44.882
−4.221
1.00
55.33


ATOM
2248
OE1
GLN
339
39.718
44.570
−3.311
1.00
58.04


ATOM
2249
NE2
GLN
339
39.235
45.786
5.155
1.00
57.36


ATOM
2250
C
GLN
339
36.640
45.818
−1.007 
1.00
27.69


ATOM
2251
O
GLN
339
37.430
46.720
−0.715
1.00
26.69


ATOM
2252
N
GLY
340
35.340
45.869
−0.744
1.00
21.87


ATOM
2253
CA
GLY
340
34.800
46.972
0.003
1.00
23.38


ATOM
2254
C
GLY
340
33.382
46.720
0.460
1.00 
24.89


ATOM
2255
O
GLY
340
32.747
45.762
−0.010
1.00
19.77


ATOM
2256
N
ILE
341
32.918
47.555
1.400
1.00
27.43


ATOM
2257
CA
ILE
341
31.557
47.502
1.942
1.00
27.30


ATOM
2258
CB
ILE
341
31.492
47.019
3.422
1.00
27.82


ATOM
2259
CG2
ILE
341
30.028
46.858
3.859
1.00
26.82


ATOM
2260
CG1
ILE
341
32.208
45.678
3.611
1.00
28.32


ATOM
2261
CD1
ILE
341
32.064
45.102
5.021
1.00
20.98


ATOM
2262
C
ILE
341
30.975
48.918
1.915
1.00
29.75


ATOM
2263
O
ILE
341
31.653
49.893
2.265
1.00
30.81


ATOM
2264
N
GLU
342
29.727
49.011
1.471
1.00
29.58


ATOM
2265
CA
GLU
342
29.002
50.263
1.393
1.00
29.98


ATOM
2266
CB
GLU
342
28.396
50.451
0.001
1.00
33.94


ATOM
2267
CG
GLU
342
27.313
51.535
−0.052
1.00
44.76


ATOM
2268
CD
GLU
342
26.970
52.004
−1.457
1.00
47.49


ATOM
2269
OE1
GLU
342
27.893
52.466
−2.164
1.00
50.86


ATOM
2270
OE2
GLU
342
25.780
51.915
−1.841
1.00
48.19


ATOM
2271
C
GLU
342
27.896
50.242
2.441
1.00
30.01


ATOM
2272
O
GLU
342
26.846
49.619
2.267
1.00
30.06


ATOM
2273
N
PHE
343
28.135
50.965
3.515
1.00
29.93


ATOM
2274
CA
PHE
343
27.213
51.059
4.624
1.00
29.27


ATOM
2275
CB
PHE
343
27.986
51.523
5.836
1.00
29.40


ATOM
2276
CG
PHE
343
29.021
50.555
6.278
1.00 
35.00


ATOM
2277
CD1
PHE
343
30.344
50.708
5.888
1.00
34.33


ATOM
2278
CD2
PHE
343
26.668
49.471
7.087
1.00
34.94


ATOM
2279
CE1
PHE
343
31.301
49.795
6.297
1.00
32.19


ATOM
2280
CE2
PHE
343
29.619
48.555
7.501
1.00
33.61


ATOM
2281
CZ
PHE
343
30.940
48.720
7.104
1.00
34.76


ATOM
2282
C
PHE
343
26.050
51.998
4.414
1.00
30.11


ATOM
2283
O
PHE
343
26.243
53.182
4.128
1.00
31.52


ATOM
2284
N
HIS
344
24.841
51.475
4.580
1.00
30.38


ATOM
2285
CA
HIS
344
23.624
52.280
4.450
1.00
32.05


ATOM
2286
CD
HIS
344
22.596
51.571
3.553
1.00
32.38


ATOM
2287
CG
HIS
344
22.806
51.818
2.083
1.00
33.83


ATOM
2288
CD2
HIS
344
23.922
51.755
1.317
1.00
32.02


ATOM
2289
ND1
HIS
344
21.788
52.209
1.238
1.00
30.81


ATOM
2290
CE1
HIS
344
22.265
52.376
0.020
1.00
29.92


ATOM
2291
NE2
HIS
344
23.558
52.106
0.040
1.00
32.00


ATOM
2292
C
HIS
344
23.076
52.567
5.855
1.00
30.97


ATOM
2293
O
HIS
344
22.927
51.648
6.648
1.00
31.67


ATOM
2294
N
THR
345
22.753
53.830
6.142
1.00
31.95


ATOM
2295 
CA
THR
345
22.290 
54.248
7.471 
1.00
31.87


ATOM
2296
CB
THR
345
23.297
55.247
8.060
1.00
30.00


ATOM
2297
OG1
THR
345
24.621
54.713
7.937
1.00
37.38


ATOM
2298
CG2
THR
345
23.012
55.496
9.513
1.00
34.79


ATOM
2299
C
THR
345
20.900
54.861
7.856
1.00
30.45


ATOM
2300
O
THR
345
20.481
55.707
6.907 
1.00
30.35


ATOM
2301
N
ARG
346
20.239
54.514
8.742
1.00
29.47


ATOM
2302
CA
ARG
346
18.931
55.064
9.021
1.00
33.75


ATOM
2303
CB
ARG
346
17.846
54.082
8.623
1.00
31.11


ATOM
2304
CG
ARG
346
17.570 
54.113
7.156
1.00
37.30


ATOM
2305
CD
ARG
346
16.698
52.963
6.778
1.00
40.39


ATOM
2306
NE
ARG
346
15.435
53.390
6.214
1.00
45.12


ATOM
2307
CZ
ARG
346
14.267
53.208
6.816
1.00
53.06


ATOM
2308
NH1
ARG
346
13.159
53.615
6.225
1.00
59.78


ATOM
2309
NH2
ARG
346
14.197
52.647
0.015
1.00
55.83


ATOM
2310
C
ARG
346
18.791
55.423
10.490
1.00
35.43


ATOM
2311
O
ARG
346
19.589
54.982
11.323
1.00
36.81


ATOM
2312
N
LEU
347
17.823
56.288
10.788
1.00
37.54


ATOM
2313
CA
LEU
347
17.548
56.712
12.156
1.00
36.68


ATOM
2314
CB
LEU
347
17.079
58.138
12.180
1.00
38.30


ATOM
2315
CG
LEU
347
16.484
58.548
13.554
1.00
41.60


ATOM
2316
CD1
LEU
347
17.617
58.883
14.514
1.00
42.74


ATOM
2317
CD2
LEU
347
15.558
59.708
23.397 
1.00
42.70


ATOM
2318
C
LEU
347
16.515
55.776
12.800 
1.00
37.67


ATOM
2319
O
LEU
347
15.596
55.252
12.136
1.00
39.32


ATOM
2320
N
GLN
348
16.699
55.528
14.090
1.00
35.33


ATOM
2321
CA
GLN
346
15.829
54.669
14.881
1.00
32.60


ATOM
2322
CB
GLN
348
16.666
53.583
15.546
1.00
33.20


ATOM
2323
CG
GLN
348
15.908
52.659
16.428
1.00
36.04


ATOM
2324
CD
GLN
348
14.852
51.898
15.687
1.00
41.50


ATOM
2325
OE1
GLN
348
13.702
52.330
15.616
1.00
40.24


ATOM
2326
OE2
GLN
348
15.219
50.731
15.162
1.00
43.99


ATOM
2327
C
GLN
348
15.321
55.653
15.905
1.00
31.09


ATOM
2328
O
GLN
348
16.075
56.120
16.753
1.00
32.14


ATOM
2329
N
PRO
349
14.058
56.060
15.784
1.00
31.17


ATOM
2330
CD
PRO
349
13.063
55.775
14.740
1.00
32.17


ATOM
2331
CA
PRO
349
13.533
57.021
16.739
1.00 
33.71


ATOM
2332
CB
PRO
349
12.323
57.590
15.993
1.00 33.92



ATOM
2333
CG
PRO
349
11.799
56.401
15.293
1.00
29.74


ATOM
2334
C
PRO
349
13.140
56.460
18.082
1.00
35.91


ATOM
2335
O
PRO
349
12.549
55.381
18.177
1.00
39.64


ATOM
2336
N
GLY
350
13.527
57.183
19.124
1.00
34.78


ATOM
2337
CA
GLY
350
13.145
56.802
20.463
1.00
29.91


ATOM
2338
C
GLY
350
11.810
57.502
20.645
1.00 
28.68


ATOM
2339
O
GLY
350
11.538
58.539
20.041
1.00
28.73


ATOM
2340
N
TYR
351
10.968 
56.949
21.492
1.00
31.04


ATOM
2341
CA
TYR
351
9.659
57.522
21.748
1.00
28.15


ATOM
2342
CB
TYR
351
8.939
56.667
22.782 
1.00 
25.11


ATOM
2343
CG
TYR
351
7.527
57.070
23.026
1.00 
28.78


ATOM
2344
CD1
TYR
351
6.530
56.806
22.090
1.00
29.11


ATOM
2345
CE1
TYR
351
5.210
57.197
22.325
1.00
36.47


ATOM
2346
CD2
TYR
351
7.181
57.727
24.199
1.00
32.05


ATOM
2347
CE2
TYR
351
5.879
58.125
24.451
1.00
37.99


ATOM
2348
CZ
TYR
351
4.892
57.866
23.517
1.00
40.84


ATOM
2349
OH
TYR
351
3.609
58.316
23.786
1.00
43.75


ATOM
2350
C
TYR
351
9.751
58.974
22.194
1.00
26.00


ATOM
2351
O
TYR
351
8.934
59.786
21.809
1.00
29.53


ATOM
2352
N
PHE
352
10.785
59.307
22.952
1.00
28.14


ATOM
2353
CA
PHE
352
10.978
60.669
23.442
1.00
30.63


ATOM
2354
CB
PHE
352
11.465
60.650
24.891
1.00
34.55


ATOM
2355
CG
PHE
352
10.616 
59.802
25.810
1.00
40.51


ATOM
2356
CD1
PHE
352
10.934
58.454
26.027
1.00
39.36


ATOM
2357
CD2 
PHE
352
9.512
60.356
26.476
1.00
39.04


ATOM
2358
CE1
PHE
352
10.174
57.670
26.891
1.00
40.28


ATOM
2359
CE2
PHE
352
8.743
59.589
27.341
1.00
40.04


ATOM
2360
C2
PHE
352
9.073
58.241
27.551
1.00
43.17


ATOM
2361
C
PHE
352
11.942
61.513
22.613
1.00
35.71


ATOM
2362
O
PHE
352
12.403
62.556
23.083
1.00
39.58


ATOM
2361
N
GLY
353
12.317
61.033
21.426
1.00
36.10


ATOM
2364
CA
GLY
353
13.201
61.791
20.549
1.00
37.76


ATOM
2365
C
GLY
353
14.656
62.037
20.933
1.00
40.10


ATOM
2366
O
GLY
353
15.544
62.011
20.072
1.00
41.93


ATOM
2367
N
LYS
354
14.928
62.314
22.195
1.00
37.55


ATOM
2368
CA
LYS
354
16.308
62.558
22.585 
1.00
40.81


ATOM
2369
CB
LYS
354
16.381
63.243
23.965
1.00
46.62


ATOM
2370
CG
LYS
354
17.574
64.209
24.106
1.00
50.82


ATOM
2371
CD
LYS
354
17.955
64.543
25.553
1.00
55.27


ATOM
2372
CE
LYS
354
19.409
65.106
25.624
1.00
59.06


ATOM
2373
NZ
LYS
354
19.989
65.226
27.011
1.00
61.08


ATOM
2374
C
LYS
354
17.097
61.243
22.597
1.00
39.24


ATOM
2375
O
LYS
354
18.321
61.243
22.467
1.00
39.45


ATOM
2376
N
ASP
355
16.387
60.130
22.746
1.00
36.63


ATOM
2377
CA
ASP
355
17.014
58.811
22.784
1.00
36.64


ATOM
2378
CB
ASP
355
16.433
57.956
23.918
1.00
38.81


ATOM
2379
CG
ASP
355
14.899
57.893
23.905
1.00
39.86


ATOM
2380
OD1
ASP
355
14.329
57.075
24.666
1.00
39.20


ATOM
2381
OD2
ASP
355
14.258
58.674
23.174
1.00
41.91


ATOM
2382
C
ASP
355
16.921
58.048
21.467 
1.00
36.41


ATOM
2383
O
ASP
355
16.687
56.839
21.459
1.00
39.46


ATOM
2384
N
SER
356
17.033
58.767
20.358
1.00
32.11


ATOM
2385
CA
SER
356
16.985
58.155
19.049
1.00
31.06


ATOM
2386
CB
SER
356
16.313
59.112
18.075
1.00
32.06


ATOM
2387
OG
SER
356
15.076
59.546
18.599
1.00
35.15


ATOM
2388
C
SER
356
18.426
57.884
18.613
1.00
32.46


ATOM
2389
O
SER
356
19.356
58.546
19.091
1.00
33.43


ATOM
2390
N
PHE
357
18.635
56.914
17.730
1.00
31.20


ATOM
2391
CA
PHE
357
19.994 
56.635
17.280
1.00
30.41


ATOM
2392
CB
PHE
357
20.662
55.552
18.150
1.00
26.65


ATOM
2393
CG
PHE
357
20.023
54.184
18.032
1.00
26.35


ATOM
2394
CD1
PHE
357
20.538
53.228
17.146
1.00
24.89


ATOM
2395
CD2
PHE
357
18.915
53.852
18.797
1.00
25.64


ATOM
2396
CE1
PHE
357
19.963
51.973
17.024
1.00
20.16


ATOM
2397
CE2
PHE
357
18.323
52.588
18.685
1.00
23.45


ATOM
2398
C2
PHE
357
18.851
51.649
17.794
1.00
25.99


ATOM
2399C
PHE
357
20.008 56.22315.825 1.0030.71







ATOM
2400
O
PHE
357
18.985
55.809
15.275
1.00
29.78


ATOM
2401
N
ASN
358
21.155
56.405
15.187
1.00
32.57


ATOM
2402
CA
ASN
358
21.326
56.021
13.795
1.00
33.87


ATOM
2403
CB
ASN
358
22.252
57.010
13.070
1.00
35.37


ATOM
2404
CG
ASN
358
21.633
58.398
12.892
1.00
37.55


ATOM
2405
OD1
ASN
358
22.327
59.358
12.511
1.00
38.07


ATOM
2406
ND2
ASN
358
20.336
58.517
13.162
1.00
37.72


ATOM
2407
C
ASN
358
21.954
54.622
13.846
1.00
33.48


ATOM
2408
O
ASN
358
22.761
54.341
14.736
1.00
31.82


ATOM
2409
N
TYR
359
21.570
53.744
12.924
1.00
33.09


ATOM
2410
CA
TYR
359
22.093
52.381
12.901
1.00
33.75


ATOM
2411
CB
TYR
359
21.098
51.434
13.563
1.00
33.52


ATOM
2412
CG
TYR
359
19.782
51.352
12.818
1.00
34.92


ATOM
2413
CD1
TYR
359
19.449
50.224
12.055
1.00
33.07


ATOM
2414
CE1
TYR
359
18.265
50.165
11.326
1.00
29.76


ATOM
2415
CD2
TYR
359
18.889
52.420
12.834
1.00
37.77


ATOM
2416
CE2
TYR
359
17.696
52.374
12.104
1.00
38.88


ATOM
2417
CZ
TYR
359
17.396
51.246
11.354
1.00
36.77


ATOM
2418
OH
TYR
359
16.235
51.223
10.618
1.00
35.92


ATOM
2419
C
TYR
359
22.231
51.978
11.454 
1.00
35.05


ATOM
2420
O
TYR
359
21.526
52.545
10.615
1.00
36.86


ATOM
2421
N
TRP
360
23.110
51.022
11.128
1.00
34.37


ATOM
2422
CA
TRP
360
23.178
50.647
9.731
1.00
32.80


ATOM
2423
CB
TRP
360
24.568
50.271
9.210
1.00
38.80


ATOM
2424
CG
TRP
360
25.172
48.996
9.571
1.00
40.63


ATOM
2425
CD2
TRP
360
25.669
48.006
8.655
1.00
39.06


ATOM
2426
CE2
TRP
360
26.392
47.049
9.423
1.00
40.29


ATOM
2427
CE3
TRP
360
25.591
47.840
7.275
1.00
27.60


ATOM
2428
CD1
TRP
360
25.564
48.606
10.808
1.00
46.32


ATOM
2429
NE1
TRP
360
26.307
47.437
10.732
1.00
48.10


ATOM
2430
CZ2
TRP
360
27.033
45.945
8.852
1.00
36.63


ATOM
2431
CZ3
TRP
360
26.224
46.743
5.709
1.00
33.68


ATOM
2432
CE2
TRP
360
26.942
45.810
7.499
1.00
36.39


ATOM
2433
C
TRP
360
22.091
49.676
9.393
1.00
29.48


ATOM
2434
O
TRP
360
21.916
48.662
10.043
1.00
28.40


ATOM
2435
N
SER
361
21.291
50.100
8.422
1.00
24.82


ATOM
2436
CA
SER
361
20.118
49.390
7.965
1.00
25.01


ATOM
2437
CB
SER
361
19.040
50.417
7.657
1.00
25.02


ATOM
2438
OG
SER
361
19.534
51.372
6.728
1.00
28.01


ATOM
2439
C
SER
361
20.272
48.481
6.770
1.00
25.86


ATOM
2440
O
SER
361
19.452
47.584
6.563
1.00
28.24


ATOM
2441
N
GLY
362
21.287
48.721
5.955
1.00
26.61


ATOM
2442
CA
GLY
362
21.470
47.893
4.775
1.00
26.68


ATOM
2443
C
GLY
362
22.843
48.075
4.174
1.00
24.88


ATOM
2444
O
GLY
362
23.624
48.876
4.681
1.00
25.16


ATOM
2445
N
ASN
363
23.135
47.385
3.078
1.00
24.77


ATOM
2446
CA
ASN
363
24.459
47.503
2.494 
1.00
25.21


ATOM
2447
CB
ASN
363
25.510
46.904
3.453
1.00
21.78


ATOM
2448
CO
ASN
363
25.509
45.366
3.479
1.00
24.03


ATOM
2449
OD1
ASN
363
26.521
44.736
3.172
1.00
24.61


ATOM
2450
ND2
ASN
363
24.396
44.762
3.893
1.00
26.86


ATOM
2451
C
ASN
363
24.598
46.810
1.166
1.00
28.38


ATOM
2452
O
ASN
363
23.737
46.009
0.783
1.00
27.10


ATOM
2453
N
TYR
364
25.684
47.158
0.477 
1.00
29.28


ATOM
2454
CA
TYR
364
26.101
46.545
−0.782
1.00
30.49


ATOM
2455
CB
TYR
364
26.241
47.570
−1.888
1.00
30.92


ATOM
2455
CG
TYR
364
24.976
47.958
−2.584
1.00
35.24


ATOM
2457
CD1
TYR
364
24.508
49.266
−2.504
1.00
37.00


ATOM
2458
CE1
TYR
364
23.391
49.671
−3.198 
1.00
37.99


ATOM
2459
CD2
TYR
364
24.280
47.047
−3.380
1.00
33.35


ATOM
2460
CE2
TYR
364
23.152
47.443
−4.082
1.00
38.54


ATOM
2461
CZ
TYR
364
22.717
48.766
−3.983
1.00
38.50


ATOM
2462
OH
TYR
364
21.612
49.214
−4.665
1.00
45.95


ATOM
2463
C
TYR
364
27.522
46.055
−0.422
1.00
32.98


ATOM
2464
O
TYR
364
28.281
46.720
0.230
1.00
33.48


ATOM
2465
N
VAL
365
27.899
44.898
−1.005
1.00
34.46


ATOM
2466
CA
VAL
365
29.266
44.442
−0.779
1.00
35.26


ATOM
2467
CB
VAL
365
29.324
43.174
0.132 
1.00
35.22


ATOM
2468
CG1
VAL
365
28.544
42.064
−0.479
1.00
36.06


ATOM
2469
CG2
VAL
365
30.774
42.761
0.415
1.00
32.31


ATOM
2470
C
VAL
365
29.946
44.221
−2.114
1.00
32.82


ATOM
2471
O
VAL
365
29.287
43.926
−3.127
1.00
29.89


ATOM
2472
N
GLU
366
31.239
44.490
−2.164
1.00
30.38


ATOM
2473
CA
GLU
366
32.002
44.298
−3.378
1.00
34.07


ATOM
2474
CB
GLU
366
32.648
45.606
−3.814
1.00
37.91


ATOM
2475
CG
GLU
366
31.688
46.701
−4.249
1.00
41.21


ATOM
2476
CD
GLU
366
32.428
47.937
4.782 
1.00
43.61


ATOM
2477
OE1
GLU
366
31.836
48.651
−5.635
1.00
40.82


ATOM
2478
OE2
GLU
366
33.591
48.184
−4.350
1.00
37.47


ATOM
2479
C
GLU
366
33.104
43.272
−3.155
1.00
33.05


ATOM
2480
O
GLU
366
33.875
43.392
−2.194
1.00
31.68


ATOM
2481
N
THR
367
33.169
42.261
−4.021
1.00
32.11


ATOM
2482 
CA 
THR
367
34.217
41.249
−3.923
1.00
31.20


ATOM
2483
CB
THR
367
33.687
39.839
−3.496
1.00
27.61


ATOM
2484
CG1
THR
367
32.743
39.357
−4.444
1.00
28.79


ATOM
2485
CG2
THR
367
33.031
39.876
−2.120
1.00
28.94


ATOM
2486
C
THR
367
34.979
41.142
−5.241
1.00
29.56


ATOM
2487
O
THR
367
34.447
41.405
−6.310
1.00
29.90


ATOM
2488
N
ARG
368
36.237
40.756 
−5.142
1.00
31.09


ATOM
2489
CA
ARG
368
37.123
40.604
−6.284
1.00
31.96


ATOM
2490
CB
ARG
368
38.3794
1.435
−6.014
1.00
29.37


ATOM
2491
CG
ARG
368
39.507
41.157
−6.926
1.00
34.48


ATOM
2492 
CD
ARG
368
40.493
40.266
−6.273
1.00
41.51


ATOM
2493
N8
ARG
368
41.404
39.670
−7.251
1.00
47.48


ATOM
2494
C2
ARG
368
42.269
40.372
−7.971
1.00
51.99


ATOM
2495
NE1
ARG
368
43.070
39.756
−8.839
1.00
54.18


ATOM
2496
NE2
ARG
368
42.336
41.697 
−7.820
1.00
53.93


ATOM
2497
C
ARG
368
37.451
39.109
−6.444
1.00
33.34


ATOM
2498
O
ARG
368
37.763
38.436
−5.464
1.00
34.00


ATOM
2499
N
PRO
369
37.391
38.580
−7.680
1.00
34.18


ATOM
2500
CD
PRO
369
37.115
39.364
−8.888
1.00
33.71


ATOM
2501
CA
PRO
369
37.656
37.186
−8.054
1.00
30.61


ATOM
2502
CB
PRO
369
37.4813
7.200
−9.561
1.00
31.74


ATOM
2503
CG
PRO
369
36.530
38.326
−9.771
1.00
35.33


ATOM
2504
C
PRO
369
39.044
36.722
−7.722
1.00
29.83


ATOM
2505
O
PRO
369
39.924
37.525
−7.398
1.00
27.32


ATOM
2506 
N
SER
370
39.255
35.417
−7.836
1.00
28.62


ATOM
2507
CA
SER
370
40.573
34.883
−7.554
1.00
31.48


ATOM
2508 
CB
SER
370
40.546
33.372
−7.433
1.00
27.56


ATOM
2509
OG
SER
370
41.406
33.022
−6.379
1.00
38.88


ATOM
2510
C
SER
370
41.553
35.358
−8.632
1.00
29.79


ATOM
2511
O
SER
370
41.136
35.864
−9.680
1.00
28.74


ATOM
2512
N
ILE
371
42.849
35.217
−8.367
1.00
29.17


ATOM
2513
CA
ILE
371
43.867
35.686
−9.297
1.00
28.44


ATOM
2514
CB
ILE
371
45.288
35.247
−8.863
1.00
24.69


ATOM
2515
CG2
ILE
371
45.532
33.810
−9.203
1.00
24.58


ATOM
2516
CG1
ILE
371
46.322
36.103
−9.586
1.00
29.48


ATOM
2517 
CD1
ILE
371
47.658
36.218
−8.891
1.00
30.22


ATOM
2518
C
ILE
371
43.560
35.358
−10.778
1.00
28.82


ATOM
2519
O
ILE
371
43.096
34.268
−11.119
1.00
28.35


ATOM
2520
N
GLY
372
43.745
36.354
−11.637
1.00
30.09


ATOM
2521
CA
GLY
372
43.456
36.181
−13.049
1.00
34.56


ATOM
2522
C
GLY
372
42.236
36.980
−13.483
1.00
36.19


ATOM
2523
O
GLY
372
41.849
36.930
−14.640
1.00
38.57


ATOM
2524
N
SER
373
41.608
37.689
−12.549
1.00
40.47


ATOM
2525
CA
SER
373
40.446
38.522
−12.841
1.00
41.94


ATOM
2526
CB
SER
373
39.187
37.678
−12.980
1.00
41.45


ATOM
2527
OG
SER
373
38.126
38.476
−13.463
1.00
43.54


ATOM
2528
C
SER
373
40.251
39.574
−11.752
1.00
45.16


ATOM
2529
O
SER
373
40.044
39.266
−10.570
1.00
46.16


ATOM
2530
N
SER
374
40.308
40.828
−12.157
1.00
48.44


ATOM
2531
CA
SER
374
40.162
41.911
−11.202
1.00
53.89


ATOM
2532 
CB
SER
374
41.048
43.071
−11.625
1.00
57.08


ATOM
2533
OG
SER
374
42.301
42.578
−12.055
1.00
68.67


ATOM
2534
C
SER
374
38.735
42.392
−11.070
1.00
53.37


ATOM
2535
O
SER
374
38.358
42.931
−10.033
1.00
53.57


ATOM
2536
N
LYS
375
37.954
42.204
−12.130
1.00
53.62


ATOM
2537
CA
LYS
375
36.565
42.646
−12.165
1.00
54.04


ATOM
2538
CB
LYS
375
35.804
41.962
−13.309
1.00
61.15


ATOM
2539
CG
LYS
375
35.604
40.453
−13.172
1.00
71.46


ATOM
2540
CD
LYS
375
34.757
39.912
−14.328
1.00
80.46


ATOM
2541
CE 
LYS
375
34.547
38.401
−14.234
1.00
85.39


ATOM
2542
NZ
LYS
375
33.824
37.872
−15.438
1.00
89.61


ATOM
2543
C
LYS
375
35.869
42.386
−10.847
1.00
49.20


ATOM
2544
O
LYS
375
35.898
41.276
−10.352
1.00
49.05


ATOM
2545
N
THR
376
35.289
43.420
−10.255
1.00
45.64


ATOM
2546
CA
THR
376
34.614
43.239
−8.991
1.00
43.45


ATOM
2547 
CB
THR
376
34.597
44.516
−8.122
1.00
47.21


ATOM
2548
CG1
THR
376
33.898
45.562
−8.803
1.00
50.56


ATOM
2549
CG2
THR
376
36.017
44.975
−7.798
1.00
48.78


ATOM
2550
C
THR
376
33.207
42.747
−9.207
1.00
40.09


ATOM
2551
O
THR
376
32.642
42.852
−10.300
1.00
35.92


ATOM
2552
N
ILE
377
32.656
42.202
−8.137
1.00
37.93


ATOM
2553
CA
ILE
377
31.326
41.653
−8.137
1.00
36.78


ATOM
2554
CB
ILE
377
31.362
40.152 
−7.774
1.00
34.83


ATOM
2555
CG2
ILE
377
29.980
39.533
−7.895
1.00
32.45


ATOM
2556
CG1
ILE
377
32.348
39.413
−8.684
1.00
32.69


ATOM
2557
CD1
ILE
377
32.748
38.041
−8.162
1.00
27.92


ATOM
2558
C
ILE
377
30.563
42.415
−7.072
1.00
39.31


ATOM
2559
O
ILE
377
30.962
42.435
−5.896
1.00
38.63


ATOM
2560
N
THR
378
29.566
43.169
−7.519
1.00
41.06


ATOM
2561
CA
THR
378
28.712
43.918
−6.616
1.00
40.06


ATOM
2562
CB
THR
378
28.209
45.243
−7.226
1.00
38.28


ATOM
2563
CG1
THR
378
29.316
46.145
−7.396
1.00
43.42


ATOM
2564
CG2
THR
378
27.163
45.891
−6.308
1.00
35.99


ATOM
2565
C
THR
378
27.536
42.999
−6.323
1.00
40.53


ATOM
2566
O
THR
378
27.024
42.310
−7.214
1.00
42.82


ATOM
2567
N
SER
379
27.153
42.959
−5.054
1.00
41.66


ATOM
2568
CA
SER
379
26.057
42.122
−4.585
1.00
37.15


ATOM
2569
CB
SER
379
26.315
41.774
−3.123
1.00
39.90


ATOM
2570
OG
SER
379
26.357
42.971
−2.344
1.00
39.97


ATOM
2571
C
SER
379
24.738
42.872
−4.840
1.00
34.85


ATOM
2572
O
SER
379
24.689
44.089
−4.869
1.00
34.30


ATOM
2573
N
PRO
380
23.838
42.148
−4.448
1.00
30.97


ATOM
2574
CD
PRO
380
23.467
40.702
−4.256
1.00
30.83


ATOM
2575
CA
PRO
380
22.355
42.837
−4.467
1.00
31.60


ATOM
2576
CB
PRO
380
21.355
41.692
−4.253
1.00
33.86


ATOM
2577
CG
PRO
380
22.064
40.484
−4.705
1.00
29.90


ATOM
2578
C
PRO
380
22.365
43.725
−3.219
1.00
31.83


ATOM
2579
O
PRO
380
23.212
43.544
−2.338
1.00
34.52


ATOM
2580
N
PHE
381
21.469
44.700
−3.144
1.00
31.79


ATOM
2581
CA
PHE
381
21.399
45.514
−1.940
1.00
30.64


ATOM
2582 
CB
PHE
381
20.547
46.761 
−2.152
1.00
26.26


ATOM
2583
CG
PHE
381
20.422
47.617
−0.932
1.00
24.77


ATOM
2584
CD1
PHE
381
21.530 
48.333
−0.452
1.00
26.36


ATOM
2585
CD2
PHE
381
19.198
47.712
−0.258
1.00
21.71


ATOM
2586
CE1
PHE
381
21.431
49.137
0.684
1.00
25.19


ATOM
2587
CE2
PHE
381
19.073
48.501
0.872
1.00
21.85


ATOM
2588
CZ 
PHE
381
20.201
49.224
1.353
1.00
27.79


ATOM
2589
C
PHE
381
20.751
44.613
−0.881
1.00
32.40


ATOM
2590
O
PHE
381
19.561
43.801
−1.185
1.00
32.67


ATOM
2591
N
TYR
382
21.225
44.746 
0.351
1.00
34.10


ATOM
2592
CA
TYR
382
20.732
43.974
1.485
1.00
30.09


ATOM
2593
CB
TYR
382
21.890
43.185
2.083
1.00
22.37


ATOM
2594
CG
TYR
382
22.562
42.226
1.140
1.00
15.64


ATOM
2595
CD1
TYR
382
23.940
42.249 
0.959
1.00
19.25


ATOM
2596
CE1
TYR
382
24.576
41.299
0.181
1.00
17.01


ATOM
2597
CD2
TYR
382
21.835
41.217
0.501
1.00
21.74


ATOM
2598
CE2
TYR
382
22.457
40.278
−0.286
1.00
17.61


ATOM
2599
CZ 
TYR
382
23.822
40.315
−0.436
1.00
20.73


ATOM
2600
OH
TYR
382
24.406
39.331
−1.176
1.00
22.81


ATOM
2601
C
TYR
382
20.220
44.975
2.530
1.00
33.35


ATOM
2602
O
TYR
382
20.899
45.969
2.818
1.00
34.99


ATOM
2603
N
GLY
383
19.014
44.748
3.051
1.00
32.94


ATOM
2604
CA
GLY
383
18.457
45.635
4.064
1.00
32.92


ATOM
2605
C
GLY
383
17.707
46.853
3.546
1.00
35.30


ATOM
2606
O
GLY
383
17.148
46.820
2.454
1.00
32.00


ATOM
2607
N
ASP
384
17.694
47.916
4.354
1.00
34.45


ATOM
2608
CA
ASP
384
17.015
49.159
4.027
1.00
33.27


ATOM
2609 
CB
ASP
384
16.294
49.698
5.241
1.00
36.97


ATOM
2610
CG
ASP
384
14.987
49.003
5.484
1.00
41.84


ATOM
2611
OD1
ASP
384
14.110
49.050
4.590
1.00
48.37


ATOM
2612
OD2
ASP
384
14.828
48.418
6.568
1.00
42.67


ATOM
2613
C
ASP
384
17.936
50.224 
3.531
1.00
35.10


ATOM
2614
O
ASP
384
19.068
50.319
3.998
1.00
34.64


ATOM
2615
N
LYS
385
17.4475
1.020
2.577
1.00
39.67


ATOM
2616
CA
LYS
385
18.212
52.128
1.969
1.00
42.47


ATOM
2617
CB
LYS
385
17.461
52.731
0.765
1.00
49.42


ATOM
2618
CG
LYS
385
17.308
51.805
−0.432
1.00
57.29


ATOM
2619
CD
LYS
385
18.609
51.672
−1.254
1.00
63.49


ATOM
2620
CE
LYS
385
18.395
50.774
−2.495
1.00
67.56


ATOM
2621
NZ
LYS
385
19.579
50.684
−3.406
1.00
67.31


ATOM
2622
C
LYS
385
18.442
53.219
2.993
1.00
39.12


ATOM
2623
O
LYS
385
17.573
53.470
3.838
1.00
43.51


ATOM
2624
N
SER
386
19.559
53.931
2.901
1.00
34.02


ATOM
2625
CA
SER
386
19.771
54.934
3.913
1.00
34.23


ATOM
2626
CB
SER
386
21.246
55.265
4.156
1.00
27.24


ATOM
2627
OG 
SER
386
21.916
55.575
2.988
1.00
29.42


ATOM
2628
C
SER
386
18.928
56.164
3.825
1.00
39.30


ATOM
2629 
O
SER
386
18.289
56.441 
2.814
1.00
45.39


ATOM
2630
N
THR
387
18.847
56.790
4.994
1.00
44.75


ATOM
2631
CA
THR
387
18.126
58.011
5.334
1.00
43.08


ATOM
2632 
CB
THR
387
17.432
57.749
6.690
1.00
45.54


ATOM
2633
OG1
THR
387
16.146
57.160
6.456
1.00
51.56


ATOM
2634
CG2
THR
387
17.365
58.983
7.581
1.00
48.46


ATOM
2635
C
THR
387
19.219
59.058
5.509
1.00
41.51


ATOM
2636
O
THR
367
19.060
60.229
5.207
1.00
45.34


ATOM
2637
N
GLU
328
20.372
58.578
5.945
1.00
39.65


ATOM
2638
CA
GLU
388
21.510
59.408
6.192
1.00
40.13


ATOM
2639
CB
GLU
388
22.079
58.996
7.537
1.00
42.68


ATOM
2640
CG
GLU
388
21.079
59.112
8.646
1.00
46.20


ATOM
2641
CD
GLU
388
20.744
60.555
8.979
1.00
51.34


ATOM
2642
OE1
GLU
388
21.607
61.454 
8.749
1.00
48.83


ATOM
2643
OE2
GLU
388
19.615
60.789 
9.496
1.00
54.12


ATOM
2644
C
GLU
388
22.554
59.136
5.115
1.00
40.71


ATOM
2645
O
GLU
388
22.342
58.275
4.252
1.00
39.83


ATOM
2646
N
PRO
389
23.702
59.825
5.183
1.00
42.10


ATOM
2647
CD
PRO
389
24.063
60.916
6.114
1.00
42.79


ATOM
2648
CA
PRO
389
24.763
59.619
4.198 
1.00
44.35


ATOM
2649 
CB
PRO
389
25.851
60.608
4.654
1.00
45.07


ATOM
2650
CG
PRO
389
25.090
61.684
5.323
1.00
43.93


ATOM
2651
C
PRO
389
25.311
58.169
4.187
1.00
45.36


ATOM
2652
O
PRO
389
25.363
57.489
5.234
1.00
46.15


ATOM
2653 
N
VAL
390
25.717
57.715
3.003
1.00
42.43


ATOM
2654
CA
VAL
390
26.286
56.379
2.838
1.00
39.18


ATOM
2655
CB
VAL
390
26.062
55.818
1.444
1.00
33.17


ATOM
2656
CG1
VAL
390
24.593
55.549
1.257
1.00
35.38


ATOM
2657
CG2
VAL
390
26.586
56.788
0.395
1.00
35.87


ATOM
2658
C
VAL
390
27.766
56.466
3.077
1.00
41.43


ATOM
2659
O
VAL
390
28.384
57.471
2.713
1.00
42.32


ATOM
2660
N
GLN
391
28.310
55.434
3.726
1.00
44.86


ATOM
2661
CA
GLN
391
29.739
55.358
4.036
1.00
47.38


ATOM
2662
CB
GLN
391
29.982
55.249
5.559
1.00
49.66


ATOM
2663
CG
GLN
391
29.536
56.490
6.359
1.00
50.20


ATOM
2664
CD
GLN
391
29.613
56.298
7.868
1.00
53.83


ATOM
2665 
OE1
GLN
391
30.599
55.765 
8.384
1.00
52.70


ATOM
2666
NE2
GLN
391
28.575
56.739 
8.583
1.00
48.35


ATOM
2667
C
GLN
391
30.334
54.159
3.299
1.00
45.72


ATOM
2668
O
GLN
391
29.836
53.032
3.392
1.00
46.80


ATOM
2669
N
LYS
392
11.412
54.420
2.571
1.00
44.47


ATOM
2670
CA
LYS
392
32.071
53.407
1.771
1.00
40.66


ATOM
2671
CB
LYS
392
32.196
53.911
0.335
1.00
42.32


ATOM
2672
CG
LYS
392
32.828
52.947
−0.666
1.00
48.87


ATOM
2673
CD
LYS
392
32.022
51.647
−0.844
1.00
51.56


ATOM
2674
CE
LYS
392
32.284
50.967 
−2.202
1.00
50.35


ATOM
2675
NZ
LYS
392
31.718
51.738
−3.365
1.00
53.19


ATOM
2676
C
LYS
392
33.439
53.116
2.328
1.00
38.02


ATOM
2677
O
LYS
392
34.230
54.024
2.578
1.00
40.88


ATOM
2678
N
LEU
393
33.692
51.839
2.562
1.00
35.52


ATOM
2679
CA
LEU
393
34.978
51.395
3.052
1.00
33.95


ATOM
2680
CB
LEU
393
34.827
50.700
4.404
1.00
30.25


ATOM
2681
CG
LEU
393
34.497
51.594
5.596
1.00
30.20


ATOM
2682
CD1
LEU
393
34.535
50.778
6.890
1.00
32.88


ATOM
2683
CD2
LEU
393
35.506
52.722
5.664 
1.003
1.84


ATOM
2684
C
LEU
393
35.528
50.418
2.014
1.00
34.73


ATOM
2685
O
LEU
393
34.796
49.539
1.543
1.00
36.19


ATOM
2686
N
SER
394
36.780
50.620
1.614
1.00
31.82


ATOM
2687
CA
SER
394
37.430
49.747
0.652
1.00
37.44


ATOM
2688
CB
SER
394
37.971
50.516
−0.541
1.00
41.95


ATOM
2689
OG
SER
394
38.489
49.617
−1.521
1.00
50.00


ATOM
2690
C
SER
394
38.591
49.051
1.312
1.00
39.64


ATOM
2691
O
SER
394
39.512
49.695
1.835
1.00
42.33


ATOM
2692
N
PHE
395
38.567
47.733
1.248
1.00
37.33


ATOM
2693
CA
PHE
395
39.605
46.933
1.846
1.00
39.32


ATOM
2694
CB
PHE
395
−38.963
45.836
2.682
1.00
34.54


ATOM
2695
CG
PHE
395
37.909
46.337
3.615
1.00
32.96


ATOM
2696
CD1
PHE
395
36.563
46.226
3.278
1.00
25.90


ATOM
2697
CD2
PHE
395
38.258
46.916
4.835
1.00
30.10


ATOM
2698
CE1
PHE
395
35.575
46.678
4.138
1.00
25.06


ATOM
2699 
CE2
PHE
395
37.270
47.376
5.708
1.00
31.10


ATOM
2700
CZ
PHE
395
35.921
47.255
5.356
1.00
27.26


ATOM
2701
C
PHE
395
40.555
46.333
0.818
1.00
42.66


ATOM
2702
O
PHE
395
41.275
45.388
1.127
1.00
43.59


ATOM
2703
N
ASP
396
40.544
46.858
−0.404
1.00
44.49


ATOM
2704
CA
ASP
396
41.434
46.355
−1.449
1.00
46.90


ATOM
2705
CB
ASP
396
41.338
47.261
−2.693
1.00
49.42


ATOM
2706 
CG
ASP
396
42.396
46.935
−3.764
1.00
55.28


ATOM
2707
OD1
ASP
396
42.247
45.919
−4.494
1.00
54.98


ATOM
2708
OD2
ASP
396
43.374
47.717
−3.884
1.00
56.58


ATOM
2709
C
ASP
396
42.879
46.293
−0.914
1.00
48.42


ATOM
2710
O
ASP
396
43.417
47.308
−0.452
1.00
51.13


ATOM
2711
N
GLY
397
43.465
45.093
−0.908
1.00
47.37


ATOM
2712
CA
GLY
397
44.836
44.908
−0.437
1.00
49.02


ATOM
2713
C
GLY
397
45.040
44.597 
1.045
1.00
49.20


ATOM
2714
O
GLY
397
46.155
44.290
1.497
1.00
50.80


ATOM
2715
N
GLN
398
43.949
44.642
1.797
1.00
48.76


ATOM
2716
CA
GLN
398
43.973
44.402
1.229
1.00
43.09


ATOM
2717
CB
GLN
398
43.194
45.515
3.957
1.00
42.33


ATOM
2718
CG
GLN
398
43.622
46.937
3.625
1.00
40.39


ATOM
2719
CD
GLN
398
45.056
47.224
4.023
1.00
41.78


ATOM
2720
OE1
GLN
398
45.473
46.965
5.149
1.00
40.33


ATOM
2721
NE2
GLN
398
45.827
47.747
3.088
1.00
46.48


ATOM
2722
C
GLN
398
43.353
43.051
3.575
1.00
39.37


ATOM
2723
O
GLN
398
42.579
42.480
2.793
1.00
35.23


ATOM
2724
N
LYS
399
43.741
42.535
4.743
1.00
36.01


ATOM
2725
CA
LYS
399
43.220
41.283
5.271
1.00
32.45


ATOM
2726
CB
LYS
399
44.354
40.298
5.627
1.00
32.95


ATOM
2727
CG
LYS
399
45.153
39.758
4.467
1.00
35.89


ATOM
2728
CD
LYS
399
44.318
38.913
3.525
1.00
45.68


ATOM
2729
CE
LYS
399
45.157
38.442
2.309
1.00
55.14


ATOM
2730
NZ 
LYS
399
44.438
37.617
1.261
1.00
52.03


ATOM
2731
C
LYS
399
42.506
41.712
6.554
1.00
28.99


ATOM
2732 
O
LYS
399
43.163
42.099
7.523
1.00
27.89


ATOM
2733
N
VAL
400
41.178
41.713
6.547
1.00
21.10


ATOM
2734
CA
VAL
400
40.433
42.091
7.736
1.00
22.51


ATOM
2735
CB
VAL
400
39.005
42.610
7.399
1.00
23.45


ATOM
2736
CG1
VAL
400
38.225
42.938
8.675
1.00
17.30


ATOM
2737
CG2
VAL
400
39.120
43.846
6.543
1.00
22.17


ATOM
2738
C
VAL
400
40.385
40.895
8.666
1.00
20.47


ATOM
2739
O
VAL
400
39.623
39.965
8.464
1.00
20.12


ATOM
2740
N
TYR
401
41.177
40.946
9.718
1.00
22.08


ATOM
2741
CA
TYR
401
41.235
39.832
10.626
1.00
23.87


ATOM
2742
CB
TYR
401
42.686
39.513
10.967
1.00
23.92


ATOM
2743
CG
TYR
401
43.399
40.624
11.667
1.00
21.62


ATOM
2744
CD1
TYR
401
43.361
40.718
13.049
1.00
23.62


ATOM
2745
CE1
TYR
401
44.024
41.725
13.718
1.00
22.25


ATOM
2746
CD2
TYR
401
44.124
41.583
10.949
1.00
23.09


ATOM
2747
CE2
TYR
401
44.791
42.607
11.602
1.00
21.21


ATOM
2748
CZ
TYR
401
44.733
42.663
12.995
1.00
26.42


ATOM
2749
OH
TYR
401
45.392
43.644
13.698
1.00
38.32


ATOM
2750
C
TYR
401
40.421
39.971
11.886
1.00
25.97


ATOM
2751
O
TYR
401
40.523
39.117
12.762
1.00
24.72


ATOM
2752
N
ARG
402
39.627
41.033
11.999
1.00
25.45


ATOM
2753
CA
ARG
402
38.797
41.206
13.181
1.00
21.27


ATOM
2754
CB
ARG
402
39.671
41.438
14.397
1.00
20.74


ATOM
2755
CG
ARG
402
38.922
41.510
15.687
1.00
19.16


ATOM
2756
CD
ARG
402
39.831
42.048
16.720
1.00
16.61


ATOM
2757
NE
ARG
402
39.323
41.788
18.050
1.00
24.94


ATOM
2758
CZ
ARG
402
40.054
41.922
19.154
1.00
34.52


ATOM
2759
NH1
ARG
402
39.521
41.650
20.337
1.00
40.03


ATOM
2760
NH2
ARG
402
41.314
42.347
19.081
1.00
29.20


ATOM
2761 
C
ARG
402
37.794
42.340
13.079
1.00
22.04


ATOM
2762
O
ARG
402
38.103
43.401
12.539
1.00
21.07


ATOM
2763
N
THR
403
36.622
42.113
13.670
1.00
23.73


ATOM
2764
CA
THR
403
35.519
43.062
13.702
1.00
22.58


ATOM
2765
CB
THR
403
34.395
42.681
12.701
1.00
26.34


ATOM
2766
CG1
THR
403
33.865
41.394
13.027
1.00
31.05


ATOM
2767
CG2
THR
403
34.930
42.618
11.297
1.00
28.24


ATOM
2768
C
THR
403
34.942
43.074
15.111
1.00
19.93


ATOM
2769
O
THR
403
34.810
42.033
15.751
1.00
17.31


ATOM
2770
N
ILE
404
34.672
44.274
15.603 
1.00
21.50


ATOM
2771
CA
ILE
404
34.117
44.490
16.941
1.00
23.42


ATOM
2772
CB
ILE
404
35.139
45.177
17.888
1.00
22.26


ATOM
2773
CG2
ILE
404
34.511
45.385
19.250
1.00
25.17


ATOM
2774
CG1
ILE
404
36.436
44.355
17.945
1.00
19.77


ATOM
2775
CG2
ILE
404
37.514
44.953
18.807
1.00
19.18


ATOM
2776
C
ILE
404
32.952
45.431
16.738
1.00
22.13


ATOM
2777
O
ILE
404
33.123
46.554
16.251
1.00
20.52


ATOM
2778
N
ALA
405
31.769
44.967
17.091
1.00
24.23


ATOM
2779
CA
ALA
405
30.566
45.761
16.903
1.00
29.85


ATOM
2760
CB
ALA
405
29.505
44.951
16.164
1.00
32.90


ATOM
2781
C
ALA
405
29.998
46.268
18.196
1.00
30.65


ATOM
2782 
O
ALA
405
30.172
45.654
19.261
1.00
32.26


ATOM
2783
N
ASN
406
29.314
47.401
16.086
1.00
33.60


ATOM
2784
CA
ASN
406
28.657
48.036
19.213
1.00
30.90


ATOM
2785
CB
ASN
406
29.353
49.328
19.575
1.00
35.26


ATOM
2786
CG
ASN
406
30.688
49.082
20.251
1.00
39.28


ATOM
2787
OD1
ASN
406
31.716
49.567 
19.796
1.00
46.28


ATOM
2788
ND2
ASN
406
30.677
48.323
21.345
1.00
41.47


ATOM
2789
C
ASN
406
27.221
48.255
18.823
1.00
27.42


ATOM
2790
O
ASN
406
26.917
48.549
17.680
1.00
31.60


ATOM
2791 
N
THR
407
26.335
48.093 
19.779
1.00
28.95


ATOM
2792
CA
THR
407
24.923
46.210
19.527
1.00
27.59


ATOM
2793
CB
THR
407
24.307
46.799
19.792
1.00
29.44


ATOM
2794
CG1
THR
407
23.752
46.264
18.585
1.00
34.58


ATOM
2795
CG2
THR
407
23.274
46.801
20.691
1.00
12.65


ATOM
2796
C
THR
407
24.312
49.344
20.376 
1.00
29.05


ATOM
2797
O
THR
407
25.039
50.103
21.043
1.00
29.87


ATOM
2798
N
ASP
408
22.994
49.517
20.272
1.00
30.16


ATOM
2799
CA
ASP
408
22.248
50.520
21.040
1.00
26.65


ATOM
2800
CB
ASP
408
22.396
51.893
20.417
1.00
26.06


ATOM
2801
CG
ASP
408
22.171
53.004
21.395
1.00
28.54


ATOM
2802
OD1
ASP
408
22.823
54.054
21.232
1.00
32.74


ATOM
2803
OD2
ASP
408
21.362
52.841
22.322
1.00
22.44


ATOM
2804
C
ASP
408
20.777
50.102
21.083
1.00
25.70


ATOM
2805
O
ASP
408
20.375
49.156
20.412
1.00
26.95


ATOM
2806 
N
VAL
409
19.998
50.740 
21.949
1.00
26.74


ATOM
2807
CA
VAL
409
18.579
50.416 
22.096
1.00
29.52


ATOM
2808
CB
VAL
409
10.318
49.460
23.308
1.00
33.88


ATOM
2809
CG1
VAL
409
18.152
48.015
22.865
1.00
32.06


ATOM
2010
CG2
VAL
409
19.450
49.583
24.330
1.00
36.32


ATOM
2811
C
VAL
409
17.750
51.675
22.354
1.00
29.41


ATOM
2812
O
VAL
409
18.284
52.726
22.744
1.00
27.31


ATOM
2813
N
ALA
410
16.438
51.524
22.171
1.00
28.05


ATOM
2814
CA
ALA
410
15.450
52.573
22.397
1.00
21.88


ATOM
2815
CB
ALA
410
15.244
53.387
21.135
1.00
18.08


ATOM
2816
C
ALA
410
14.196
51.772
22.714
1.00
22.70


ATOM
2817
O
ALA
410
13.674
51.018 
21.905
1.00
19.65


ATOM
2818
N
ALA
411
13.805
51.820
24.003
1.00
27.52


ATOM
2819
CA
ALA
411
12.623
51.091
24.470
1.00
31.81


ATOM
2820
CB
ALA
411
12.873
50.502
25.829
1.00
33.93


ATOM
2821
C
ALA
411
11.431
52.029
24.525
1.00
34.20


ATOM
2822
O
ALA
411
11.535
53.147
25.038
1.00
34.95


ATOM
2823
N
TRP
412
10.306
51.592
23.987
1.00
33.77


ATOM
2824
CA
TRP
412
9.134
52.436
23.996
1.00
39.98


ATOM
2825
CB
TRP
412
8.392
52.358
22.669
1.00
41.61


ATOM
2826
CG
TRP
412
9.054
53.098
21.571
1.00
43.46


ATOM
2827
CD2
TRP
412
8.430
53.596
20.392
1.00
45.56


ATOM
2828
CE2
TRP
412
9.440
54.195
19.607
1.00
42.47


ATOM
2829
CE3
TRP
412
7.110
53.590
19.916
1.00
46.54


ATOM
2830
CD1
TRP
412
10.376 
53.412
21.467
1.00
44.40


ATOM
2831
NE1
TRP
412
10.617 
54.067
20.288
1.00
43.38


ATOM
2832
CZ2
TRP
412
9.177
54.788
18.377
1.00
45.51


ATOM
2833
CZ3
TRP
412
6.844
54.179
18.689
1.00
46.75


ATOM
2834
CH2
TRP
412
7.877
54.770
17.931
1.00
48.56


ATOM
2835
C
TRP
412
8.213
52.038
25.114
1.00
44.25


ATOM
2836
O
TRP 
412
0.109
50.853
25.444
1.00
42.52


ATOM
2837
N
PRO 
413
7.519
53.028
25.716
1.00
50.07


ATOM
2838
CD
PRO
413
7.624
54.477
25.453
1.00
50.83


ATOM
2839
CA
PRO
413
6.584
52.781
26.815
1.00
50.92


ATOM
2840
CB
PRO
413
5.903
54.138
26.979
1.00
50.26


ATOM
2841
CG
PRO
413
7.019
55.079
26.697
1.00
49.66


ATOM
2842
C
PRO
413
5.599
51.690
26.424
1.00
51.13


ATOM
2843
O
PRO
413
5.244
50.846
27.240
1.00
53.47


ATOM
2844 
N
ASN
414
5.227
51.674
25.148
1.00
52.31


ATOM
2845
CA
ASN 
414
4.291
50.687
24.624
1.00
54.17


ATOM
2846
CB
ASN
414
3.559
51.238
23.388
1.00
58.82


ATOM
2847
CG
ASN
414
4.490
51.960
22.411
1.00
61.33


ATOM
2848
OD1
ASN 
414
4.680
53.184
22.501
1.00
64.05


ATOM
2849
ND2
ASN 
414
5.073
51.210
21.480
1.00
55.75


ATOM
2850
C
ASN 
414
4.947
49.338
24.321
1.00
54.03


ATOM
2851
O
ASN
414
4.481
48.586
23.466
1.00
55.04


ATOM
2852
N
GLY
415
6.058
49.060
24.992
1.00
51.36


ATOM
2853
CA
GLY
415
6.737
47.792
24.811
1.00
50.33


ATOM
2854 
C
GLY
415
7.639
47.544
23.614
1.00
49.60


ATOM
2855
O
GLY 
415
0.402
46.582
23.615
1.00
55.05


ATOM
2856
N
LYS
416
7.578
48.375
22.591
1.00
46.50


ATOM
2857
CA
LYS
416
8.423
48.147
21.431
1.00
43.10


ATOM
2858
CB
LYS
416
7.982
49.065
20.294
1.00
45.88


ATOM
2859
CG
LYS
416
6.489
49.015
19.989
1.00
40.22


ATOM
2860
CD
LYS
416
6.139
47.815
19.142
1.00
53.88


ATOM
2861
CE
LYS
416
4.658
47.762
18.779
1.00
53.22


ATOM
2862
NZ
LYS
416
4.374
46.692
17.766
1.00
54.21


ATOM
2863
C
LYS
416
9.887
48.429
21.775
1.00
39.40


ATOM
2864
O
LYS
416
10.197
49.492
22.311
1.00
39.18


ATOM
2865
N
VAL
417
10.771
47.453
21.571
1.00
36.07


ATOM
2866
CA
VAL
417
12.198
47.682
21.818
1.00
33.10


ATOM
2867 
CB
VAL
417
12.851
46.648
22.743
1.00
32.27


ATOM
2868
CG1
VAL
417
14.357
46.934
22.860
1.00
29.20


ATOM
2869
CG2
VAL 
417
12.234
46.738
24.127
1.00
30.38


ATOM
2870
C
VAL 
417
12.893
47.682
20.469
1.00
33.32


ATOM
2871
O
VAL 
417
12.521
46.923
19.553
1.00
32.49


ATOM
2872
N
TYR
418
13.877
48.562
20.332
1.00
32.46


ATOM
2873
CA
TYR
418
14.584
48.700
19.078
1.00
30.70


ATOM
2874 
CB 
TYR 
418
14.201
50.034
18.430
1.00
35.09


ATOM
2875
CG 
TYR 
418
12.723
50.142
18.087
1.00
39.67


ATOM
2876 
CD1
TYR
418
11.830 
50.796
18.939
1.00
41.36


ATOM
2877
CE1
TYR 
418
10.468 
50.837
18.656
1.00
41.55


ATOM
2878
CD2
TYR 
418
12.210
49.539
16.938
1.00
42.74


ATOM
2879
CE2
TYR
418
10.858
49.579
16.649
1.00
41.49


ATOM
2880 
CZ 
TYR
418
9.997
50.224
17.512
1.00
40.58


ATOM
2881 
OH
TYR 
418
8.660
50.227
17.231
1.00
43.39


ATOM
2882 
C
TYR 
418
16.087
48.604
19.217
1.00
31.90


ATOM
2883
O
TYR 418
16.674
49.292
20.050
1.00
34.09



ATOM
2884
N
LEU
419
16.697
47.794
18.349
1.00
35.53


ATOM
2885
CA
LEU
419
18.145
47.575
18.313
1.00
35.73


ATOM
2886
CB
LEU
419
18.470
46.108
18.875
1.00
40.81


ATOM
2887
CG
LEU
419
18.374 
46.005
20.396
1.00
45.56


ATOM
2888 
CD1
LEU
419
17.661
44.692
20.771
1.00
47.76


ATOM
2889
CD2
LEU
419
19.783
46.064
20.993
1.00
47.90


ATOM
2890
C
LEU
419
18.739
47.717
16.898
1.00
34.04


ATOM
2891
O
LEU
419
18.017
47.650
15.889
1.00
34.32


ATOM
2892
N
GLY
420
20.049
47.940
16.841
1.00
29.29


ATOM
2893
CA
GLY
420
20.743
48.085
15.576
1.00
26.65


ATOM
2894
C
GLY
420
22.211
48.353
15.836
1.00
27.14


ATOM
2895
O
GLY
420
22.575
48.680
16.964
1.00
28.38


ATOM
2896
N
VAL
421
23.046
48.253
14.803
1.00
26.69


ATOM
2897 CA
VAL
421
24.490
48.452
14.924
1.00
24.73



ATOM
2898
CB
VAL
421
25.274
47.527
13.945 
1.00
26.82


ATOM
2899
CG1
VAL
421
26.784
47.789
14.031
1.00
25.39


ATOM
2900
CG2
VAL
421
24.993
46.080
14.252
1.00
23.09


ATOM
2901
C
VAL
421
24.878
49.893
14.640
1.00
27.15


ATOM
2902
O
VAL
421
24.661
50.401
13.539
1.00
30.83


ATOM
2903
N
THR
422
25.535
50.521
15.605
1.00
27.69


ATOM
2904
CA
THR
422
25.946
51.910
15.470
1.00
28.13


ATOM
2905 
CB
THR
422
25.717
52.692
16.789
1.00
27.76


ATOM
2906 
OG1
THR
422
26.642
52.239
17.782
1.00
26.20


ATOM
2907
CG2
THR
422
24.285
52.503
17.289
1.00
22.77


ATOM
2908
C
THR
422
27.414
52.047
15.133
1.00
29.17


ATOM
2909
O
THR
422
27.864
53.111
14.725
1.00
31.06


ATOM
2910
N
LYS
423
28.167
50.974
15.315
1.00
31.17


ATOM
2911
CA
LYS
423
29.591
51.032
15.079
1.00
30.80


ATOM
2912
CH
LYS
423
30.242
51.794
16.234
1.00
27.04


ATOM
2913
CG
LYS
423
31.689
52.148
16.020
1.00
27.11


ATOM
2914
CD
LYS
423
32.186
52.755
17.273
1.00
31.47


ATOM
2915
CE
LYS
423
33.668
52.750
17.356
1.00
32.44


ATOM
2916
NZ
LYS
423
33.955
53.029
18.792
1.00
43.38


ATOM
2917
C
LYS
423
30.247
49.662
14.914
1.00
31.76


ATOM
2918
O
LYS
423
29.828
48.662
15.529
1.00
32.10


ATOM
2919
N
VAL
424
31.240
49.629
14.026
1.00
31.62


ATOM
2920
CA
VAL
424
32.015
48.435
13.715
1.00
30.00


ATOM
2921
CB
VAL
424
31.408
47.626
12.543
1.00
26.10


ATOM
2922
CG1
VAL
424
32.157
46.316
12.382
1.00
24.90


ATOM
2923
CG2
VAL
424
29.915
47.367
12.769 
1.00
23.72


ATOM
2924
C
VAL
424
33.430
48.856
13.329
1.00
29.28


ATOM
2925
O
VAL
424
33.622
49.766
12.524
1.00
29.28


ATOM
2926
N
ASP
425
34.409
48.247
13.984
1.00
32.53


ATOM
2927
CA
ASP
425
35.816
48.508
13.720
1.00
32.54


ATOM
2928
CB
ASP
425
36.598
48.641
15.021
1.00
34.95


ATOM
2929 
CG
ASP
425
36.257
49.900
15.769
1.00
45.99


ATOM
2930
OD1
ASP
425
36.132 
50.961
15.117 
1.00
46.60


ATOM
2931
OD2
ASP
425
36.107
49.828
17.010
1.00
52.51


ATOM
2932
C
ASP
425
36.369
47.329
12.954
1.00
30.71


ATOM
2933
O
ASP
425
36.189
46.176
13.364
1.00
28.66


ATOM
2934
N
PHE
426
37.035
47.619
11.845
1.00
30.44


ATOM
2935
CA
PHE
426
37.641
46.599 
11.003
1.00
27.35


ATOM
2936
CB
PHE
426
37.265
46.824
9.535
1.00
23.83


ATOM
2937
CG
PHE
426
35.811
46.617
9.260
1.00
22.42


ATOM
2938
CD1
PHE
426
34.917
47.675
9.353
1.00
29.21


ATOM
2939
CD2
PHE
426
35.325
45.356
8.952
1.00
23.84


ATOM
2940
CE1
PHE
426
33.535
47.482
9.143
1.00
30.42


ATOM
2941
CE2
PHE
426
33.953
45.141
8.738
1.00
28.45


ATOM
2942
CZ
PHE
426
33.054
46.211
8.836 
1.00
25.84


ATOM
2943
C
PHE
426
39.143
46.651
11.165
1.00
27.60


ATOM
2944
O
PHE
426
39.764
47.605
10.715 
1.00
30.18


ATOM
2945
N
SER
427
39.704 
45.697
11.914
1.00
28.92


ATOM
2945 
CA
SER
427
41.159 
45.613 
12.097
1.00
31.13


ATOM
2947
CB
SER
427
41.527
44.834
13.354
1.00
23.47


ATOM
2948
OG
SER
427
41.323
45.630
14.486
1.00
34.58


ATOM
2949
C
SER
427
41.734
44.896
10.885
1.00
30.97


ATOM
2950
O
SER
427
41.582
43.678
10.741
1.00 
34.75


ATOM
2951
N
GLN
428
42.388
45.647
10.019
1.00
32.50


ATOM
2952
CA
GLN
428
42.943
45.066
8.819
1.00
34.39


ATOM
2953
CB
GLN
428
42.474
45.849
7.597
1.00
35.19


ATOM
2954
CG
GLN
428
42.655
47.358
7.703
1.00
36.26


ATOM
2955
CD
GLN
428
41.675
48.109
6.635
1.00
37.21


ATOM
2956
OE1 
GLN
428
40.922
47.576
6.041
1.00
37.62


ATOM
2957
NE2 
GLN
428
42.263
49.357
6.395
1.00
37.30


ATOM
2958
C
GLN
428
44.445
45.024
8.895
1.00
34.53


ATOM
2959
O
GLN
428
45.047
45.761
9.658
1.00
32.24


ATOM
2960
N
TYR
429
45.026
44.081
6.168
1.00
39.80


ATOM
2961
CA
TYR
429
46.465
43.909
8.113
1.00
43.52


ATOM
2962
CB
TYR
429
46.867
42.578
8.733
1.00
45.24


ATOM
2963
CG
TYR
429
46.340
42.256
8.618
1.00
44.33


ATOM
2964
CD1 
TYR
429
49.285
42.965
9.350
1.00
44.13


ATOM
2965
OE1 
TYR
429
50.647
42.652
9.270
1.00
46.61


ATOM
2966
CD2 
TYR
429
48.764
41.222
7.794
1.00
45.15


ATOM
2967
CE2 
TYR
429
50.135
40.897
7.709
1.00
48.28


ATOM
2968
CZ
TYR
429
51.064
41.614
8.451
1.00
48.90


ATOM
2969
OH
TYR
429
52.400
41.271
8.405
1.00
49.66


ATOM
2970
C
TYR
429
46.905
43.961
6.653
1.00
48.69


ATOM
2971
O
TYR
429
46.203
43.476
5.759
1.00
46.50


ATOM
2972
N
ASP
430
48.069
44.560
6.431
1.00
54.63


ATOM
2973
CA
ASP
430
48.649
44.716
5.112
7.00
58.67


ATOM
2974
CS
ASP
430
49.064
46.175
4.942
1.00
58.82


ATOM
2975
CG
ASP
430
49.474
46.522
3.518
1.00
63.70


ATOM
2976
OD1 
ASP
430
49.781
45.612
2.709
1.00
62.99


ATOM
2977
OD2 
ASP
430
49.494
47.737
3.211
1.00
65.11


ATOM
2978
C
ASP
430
49.874
43.798
5.015
1.00
63.15


ATOM
2979
O
ASP
430
50.820
43.932
5.790
1.00
62.58


ATOM
2980
N
ASP
431
49.846
42.865
4.065
1.00
69.35


ATOM
2981
CA
ASP
431
50.951
41.916
3.852
1.00
74.25


ATOM
2982
CB
ASP
431
50.578
40.849
2.802
1.00
78.72


ATOM
2983
CG
ASP
431
49.404
39.965
3.231
1.00
63.39


ATOM
2984
OD1
ASP
431
49.588
39.108
4.127
1.00
86.73


ATOM
2985
OD2
ASP
431
48.299
40.117
2.657
1.00
85.57


ATOM
2986
C
ASP
431
52.189
42.659
3.365
1.00
74.94


ATOM
2987
O
ASP
431
53.265
42.526
3.937
1.00
74.05


ATOM
2988
N
GLN
432
52.006
43.437
2.300
1.00
77.50


ATOM
2989
CA
GLN
432
53.067
44.230
1.683
1.00
78.85


ATOM
2990
CB
GLN
432
52.469
45.250
0.709
1.00 
84.24


ATOM
2991
CG
GLN
432
52.081
44.770
−0.664
1.00
94.21


ATOM
2992
CD
GLN
432
51.874
45.945
−1.635
1.00
101.21


ATOM
2993
OE1
GLN
432
51.963
45.777
−2.856
1.00
102.84


ATOM
2994
NE2
GLN
432
51.620
47.141
−1.092
1.00
103.92


ATOM
2995
C
GLN
432
53.875
45.043
2.683
1.00
76.88


ATOM
2996
O
GLN
432
55.015
44.727
3.020
1.00
75.05


ATOM
2997
N
LYS
433
53.245
46.122
3.122
1.00
74.75


ATOM
2998
CA
LYS
433
53.841
47.075
4.032
1.00
73.23


ATOM
2999
CB
LYS
433
53.030
48.372
3.965
1.00
77.09


ATOM
3000
CG
LYS
433
52.809
48.809
2.501
1.00
82.48


ATOM
3001
CD
LYS
433
51.969
50.069
2.321
1.00
85.49


ATOM
3002
CE
LYS
433
51.789
50.363
0.628
1.00
85.34


ATOM
3003
NZ
LYS
433
51.088
51.648
0.574
1.00
83.39


ATOM
3004
C
LYS
433
53.963
46.549
5.445
1.00
70.28


ATOM
3005
O
LYS
433
54.678
47.139
6.266
1.00
69.41


ATOM
3006
N
ASN
434
53.359
45.409
5.711
1.00
70.07


ATOM
3007
CA
ASN
434
53.424
44.780
7.025
1.00
69.13


ATOM
3008
CB
ASN
434
54.833
44.269
7.292
1.00
72.41


ATOM
3009
CG 
ASN
434
54.838
43.081
8.213
1.00
77.33


ATOM 
3010
OD1
ASN
434
54.802
43.220
9.436
1.00
80.62


ATOM
3011
ND2
ASN 
434
54.833
41.892
7.631
1.00
82.09


ATOM
3012
C
ASN 
434
53.018
45.790
8.099
1.00
66.04


ATOM
3013
O
ASN
434
53.745
46.042
9.055
1.00
66.81


ATOM
3014
N
GLU 
435
51.862
46.399
7.896
1.00
63.11


ATOM
3015
CA
GLU
435
51.339
47.376
8.828
1.00
60.05


ATOM
3016
CB
GLU
435
51.279
48.762
8.171
1.00
65.39


ATOM
3017
CG
GLU
435
50.404
48.827
6.908
1.00
71.11


ATOM
3018
CD
GLU
435
50.166
50.249
6.398
1.00
76.12


ATOM 
3019
OE1
GLU
435
51.151
50.987
6.158
1.00
77.71


ATOM
3020
OE2
GLU
435
48.985
50.623
6.221
1.00
76.57


ATOM
3021 
C
GLU 435
49.933
46.940
9.207
1.00
56.46



ATOM
3022
O
GLU
435
49.271
46.226
8.443
1.00
53.33


ATOM
3023
N
THR
436
49.513
47.310
10.412
1.00
52.67


ATOM
3024
CA
THR
436
40.172
47.011
10.889
1.00
48.22


ATOM
3025
CB
THR
436
48.180
46.265
12.243
1.00
49.49


ATOM 
3026
CG1
THR 
436
48.928
47.011
13.217
1.00
53.64


ATOM
1027 
CG2
THR
436
48.706
44.882
12.074
1.00
50.64


ATOM
3028
C
THR
436
47.473
48.358
11.032
1.00
44.20


ATOM
3029
O
THR
436
48.120
49.373
11.308
1.00
43.15


ATOM 
3030
N
SER
437
46.172
48.303
10.784
1.00
39.81


ATOM
3032 
CA 
SER 
437
45.404
49.610
10.876
1.00
35.03


ATOM
3032
CB
SER
437
45.525
50.401
9.567
1.00
34.84


ATOM 
3033
OG
SER
437
45.215
49.603
8.130
1.00
26.92


ATOM
3034
C
SER
437
43.954
49.262
11.147
1.00
38.35


ATOM 
3035
O
SER 
437
43.571
48.082
11.142
1.00
40.79


ATOM
3036
N
THR 
438
43.138
50.288
11.354
1.00
37.88


ATOM
3037
CA
THR
438
41.723
50.088
11.610
1.00
31.21


ATOM 
3038
CB
THR
438
41.421
50.443
13.091
1.00
30.02


ATOM
3039
CG1
THR 
438
42.206
49.607
13.943
1.00
33.55


ATOM
3040
CG2
THR
438
39.981
50.224
13.428
1.00
32.35


ATOM
3041
C
THR 
438
40.909
50.974
10.672
1.00
31.00


ATOM
3042
O
THR
438
41.434
51.916
10.084
1.00
31.16


ATOM
3043
N
GLU
439
39.676
50.576
10.416
1.00
30.24


ATOM
3044
CA
GLU
439
38.768
51.358
9.602
1.00
34.37


ATOM
3045
CB
GLU
439
38.611
50.789
8.204
1.00
40.27


ATOM
3046
CG
GLU
439
39.717
51.176
7.242
1.00
42.06


ATOM
3047
CD
GLU
439
39.296
50.989
5.805
1.00
40.04


ATOM
3048
OE1
GLU
439
39.526
49.892
5.232
1.00
36.27


ATOM
3049
OE2
GLU 
439
38.711
51.952
5.267
1.00
39.88


ATOM
3050
C
GLU
439
37.478
51.222
10.377
1.00
37.64


ATOM
3051
O
GLU
439
37.216
50.158
10.948
1.00
39.86


ATOM
3052
N
THR
440
36.614
52.224
10.297
1.00
37.34


ATOM
3053
CA
THR
440
35.409
52.209
11.108
1.00
34.42


ATOM
3054
CB
THR
440
35.649
51.100
12.268
1.00
35.98


ATOM 
3055
CG1
THR
440
36.922
52.904
12.871
1.00
36.26


ATOM 
3056
CG2
THR
440
34.523
53.111
13.294
1.00
40.16


ATOM
3057 
C
THR
440
34.076
52.624
10.496
1.00
33.02


ATOM 
3058
O
THR
440
34.012
53.522
9.668
1.00
32.99


ATOM
3059
N
TYR
441
33.005
51.984
10.947
1.00
34.71


ATOM 
3060
CA
TYR
441
31.664
52.382
10.548
1.00
32.57


ATOM
3061
CB
TYR
441
30.798
51.202
10.102
1.00
30.07


ATOM
3062 
CG
TYR
441
29.315
51.543
10.127
1.00
30.12


ATOM
3063
CD1
TYR
441
28.777
52.454 
9.222
1.00
28.88


ATOM
3064 
CE1
TYR
441
27.456
52.877
9.325
1.00
29.33


ATOM
3065
CD2
TYR
441
28.478
51.046
11.135
1.00
29.87


ATOM
3066
CE2
TYR 
441
27.164
51.462
11.245
1.00
27.38


ATOM
3067
CZ 
TYR
441
26.660
52.384
10.337
1.00
29.54


ATOM
3068
OH
TYR
441
25.372
52.851
10.468
1.00
30.14


ATOM
3069
C
TYR
441
31.047
52.990
11.815
1.00
34.37


ATOM
3070
O
TYR
441
30.872
52.289
12.802
1.00
33.76


ATOM
3071
N
ASP
442
30.749
54.286
11.791
1.00
35.00


ATOM
3072
CA
ASP
442
30.131
54.987
12.915
1.00
36.42


ATOM
3073
CB
ASP
442
31.069
56.096
13.429
1.00
42.66


ATOM
3074
CG
ASP
442
30.795
56.488
14.697
1.00
48.14


ATOM
3075
OD1
ASP
442
29.611
56.518
15.319
1.00
50.77


ATOM
3076
OD2
ASP
442
31.775
56.770
15.630
1.00
49.26


ATOM
3077
C
ASP
442
28.834
55.595
12.371
1.00
38.05


ATOM
3078
O
ASP
442
28.861
56.412
11.451
1.00
37.61


ATOM
3079
N
SER
443
27.694
55.195 
12.924
1.00
39.24


ATOM
3080
CA
SER
443
26.406
55.697
12.456
1.00
40.93


ATOM
3081
CB
SER
443
25.257
54.972
13.146
1.00
43.62


ATOM
3082
OG 
SER
443
25.233
55.289
14.529
1.00
44.57


ATOM
3083
C
SER
443
26.289
57.160 
12.714
1.00
42.03


ATOM
3084
O
SER
443
25.411
57.851
12.174
1.00
39.08


ATOM
3085
N
LYS
444
27.130
57.661
13.620
1.00
46.56


ATOM
3086
CA
LYS
444
27.179
59.063
13.977
1.00
51.18


ATOM
3087
CB
LYS
444
27.357
59.894
12.706
1.00
53.90


ATOM
3088
CG 
LYS
444
28.579
59.425
11.922
1.00
62.90


ATOM
3089
CD
LYS
444
28.7196
0.075
10.563
1.00
73.49


ATOM
3090
CE
LYS
444
30.022
59.640
9.895
1.00
77.94


ATOM
3091
NZ
LYS
444
30.378
60.504
8.729
1.00
84.38


ATOM
3092
C
LYS
444
26.062
59.589
14.892
1.00
51.23


ATOM
3093
O
LYS
444
25.898
60.806
15.039
1.00
52.96


ATOM
3094
N
ARG
445
25.307
58.667
15.496
1.00
48.51


ATOM
3095
CA 
ARG
445
24.265
59.004
16.468
1.00
45.71


ATOM
3096
CB
ARG
445
22.967
59.507
15.832
1.00
46.38


ATOM
3097
CG
ARG
445
22.092
60.234
16.859
1.00
44.46


ATOM
3098
CD 
ARG
445
20.753
60.743
16.351
1.00
45.51


ATOM
3099
NE
ARG
445
19.999
61.330
17.464
1.00
52.32


ATOM
3100
CZ
ARG
445
18.887
62.053
17.347
1.00
53.85


ATOM
3101
NH1
ARG
445
18.294
62.533
18.437
1.00
55.79


ATOM
3102
NH2
ARG
445
18.351
62.286
16.155
1.00
58.42


ATOM
3103
C
ARG
445
23.975
57.834
17.411
1.00
44.59


ATOM
3104
O
ARG
445
23.439
56.801
17.012
1.00
42.64


ATOM
3105
N
ASN
446
24.333
58.018
18.671
1.00
47.32


ATOM
3106
CA
ASN
446
24.125
56.995
19.683
1.00
51.50


ATOM
3107
CB
ASN
446
25.218
55.918
19.582
1.00
50.30


ATOM
3108
CG
ASN
446
26.606
56.478
19.825
1.00
50.32


ATOM
3109
OD1
ASN
446
27.349
56.754
18.882
1.00
52.97


ATOM
3110
ND2
ASN
446
26.958
56.666
21.088
1.00
49.49


ATOM
3111
C
ASN
446
24.128
57.608
21.078
1.00
52.00


ATOM
3112
O
ASN
446
24.866
58.559
21.351
1.00
53.53


ATOM
3113
N
ASN
447
23.336
57.015
21.967
1.00
53.99


ATOM
3114
CA
ASN
447
23.195
57.460
23.358
1.00
54.97


ATOM
3115
CB 
ASN
447
21.887
56.927
23.940
1.00
53.00


ATOM
3116
CG
ASN
447
20.722
57.051
22.976
1.00
54.20


ATOM
3117
OD1
ASN
447
20.312
58.160
22.629
1.00
59.45


ATOM
3118
ND2
ASN
447
20.189
55.916
22.530
1.00
53.02


ATOM
3119
C
ASN
447
24.345
56.951
24.222
1.00
57.40


ATOM
3120
O
ASN
447
24.547
57.409
25.340
1.00
62.75


ATOM
3121
N
GLY
448
25.075
55.981
23.689
1.00
58.44


ATOM
3122
CA
GLY
448
26.192
55.389
24.396
1.00
56.36


ATOM
3123
C
GLY
448
26.432
54.065
23.700
1.00
53.77


ATOM
3124
O
GLY
448
25.747
53.771
22.717
1.00
58.09


ATOM
3125
N
HIS
449
27.376
53.258
24.162
1.00
49.50


ATOM
3126
CA 
HIS
449
27.599
52.007
23.450
1.00
48.10


ATOM
3127
CB
HIS
449
29.005
51.934
22.830
1.00
55.56


ATOM
3128
CG
HIS
449
29.141
52.749
21.581
1.00
61.28


ATOM
3129
CD2
HIS
449
29.963
53.783
21.278
1.00
61.16


ATOM
3130
ND1
HIS
449
28.310
52.584
20.450
1.00
63.15


ATOM
3131
CE1
HIS
449
28.613
53.486
19.576
1.00
65.47


ATOM
3132
NE2 
HIS
449
29.610
54.226
20.030
1.00
65.11


ATOM
3133
C
HIS
449
27.338
50.745
24.196
1.00
40.97


ATOM
3134
O
HIS
449
28.120
50.321
25.031
1.00
42.17


ATOM
3135
N
VAL
450
26.212
50.143
23.908
1.00
33.34


ATOM
3136
CA
VAL
450
25.933
48.883
24.516
1.00
33.89


ATOM
3137
CB
VAL
450
24.525
48.441
24.179
1.00
27.68


ATOM
3138
CG1
VAL
450
24.214
47.106
24.811
1.00
23.45


ATOM
3139
CG2 
VAL
450
23.555
49.506
24.621
1.00
19.28


ATOM
3140
C
VAL
450
26.961
48.066 
23.742 
1.00
42.79


ATOM
3141
O
VAL
450
27.421
48.496 
22.674
1.00
48.77


ATOM
3142
N
SER
451
27.392
46.937
24.273
1.00
47.08


ATOM
3143
CA
SER
451
28.383
46.149
23.550
1.00
46.69


ATOM
3144
CB
SER
451
29.418
45.553
24.529
1.00
49.40


ATOM
3145
OG
SER
451
30.187
46.575
25.155
1.00
52.97


ATOM
3146
C
SER
451
27.758
45.054
22.677
1.00
44.69


ATOM
3147
O
SER
451
26.524
44.869
22.643
1.00
43.38


ATOM
3148
N
ALA
452
28.612
44.394
21.904
1.00
40.41


ATOM
3149
CA
ALA
452
28.181
43.315
21.037
1.00
37.56


ATOM
3150
CB
ALA
452
27.379
43.865
19.841
1.00
35.98


ATOM
3151
C
ALA
452
29.378
42.474
20.577
1.00
35.17


ATOM
3152 
O
ALA
452
30.445
42.482
21.188
1.00
34.47


ATOM
3153
N
GLN
453
29.215
41.832
19.438
1.00
31.36


ATOM
3154
CA
GLN
453
30.208
40.947
18.818
1.00
28.35


ATOM
3155
CB
GLN
453
29.638
40.360
17.578
1.00
31.30


ATOM
3156
CG
GLN
453
30.246
39.018
17.163
1.00
32.89


ATOM
3157
CD
GLN
453
29.737
38.530
15.832
1.00
31.23


ATOM
3158
OE1
GLN
453
30.143
39.025
14.779
1.00
34.14


ATOM
3159 
NE2
GLN 
453
28.845
37.556
15.869
1.00
28.65


ATOM
3160
C
GLN
453
31.681
41.343
18.675
1.00
25.25


ATOM
3161
O
GLN
453
32.005
42.349
18.039
1.00
25.08


ATOM
3162
N
ASP
454
32.565
40.513
19.222
1.00
24.22


ATOM
3163
CA
ASP
454
33.998
40.645
19.019
1.00
23.88


ATOM
3164
CB
ASP
454
34.776
40.663
20.321
1.00
23.71


ATOM
3165
CG
ASP
454
36.292
40.678
20.099
1.00
27.65


ATOM
3166
OD1
ASP
454
36.752
40.687
18.941
1.00
26.59


ATOM
3167
OD2
ASP
454
37.040
40.670
21.098
1.00
34.10


ATOM
3168
C
ASP
454
34.274
39.332
18.299
1.00
28.07


ATOM
3169
O
ASP
454
33.990
38.257
18.841
1.00
26.35


ATOM
3170
N
SER
455
34.800
39.409
17.077
1.00
30.04


ATOM
3171
CA
SER
455
35.073
38.204
16.273
1.00
27.99


ATOM
3172
CB
SER
455
35.589
38.575
14.877
1.00
23.39


ATOM
3173
OG
SER
455
36.916
39.063
14.946
1.00
32.54


ATOM
3174
C
SER
455
35.966
37.112
16.882
1.00
26.74


ATOM
3175
O
SER
455
35.650
35.928
16.736
1.00
28.30


ATOM
3176
N
ILE
456
37.057
37.482
17.563
1.00
23.67


ATOM
3177
CA
ILE
456
37.948
36.485
18.155
1.00
18.04


ATOM
3178
CB
ILE
456
39.083
37.138
18.933
1.00
23.55


ATOM
3179
CG2
ILE
456
39.990
37.911
17.978
1.00
17.58


ATOM
3180
CG1
ILE
456
38.498
38.012
20.047
1.00
30.14


ATOM
3181
CD1
ILE
458
39.487
38.426 
21.128
1.00
35.57


ATOM
3182
C
ILE
456
37.246
35.486 
19.077
1.00
20.83


ATOM
3183
O
ILE
456
37.703
34.354
19.260
1.00
16.93


ATOM
3184
N
ASP
457
36.138
35.896
19.675
1.00
22.41


ATOM
3185
CA
ASP
457
35.416
34.996
20.550
1.00
27.43


ATOM
3186
CB
ASP
457
34.324
35.751
21.328
1.00
34.30


ATOM
3187
CG
ASP
457
34.900
36.788
22.308
1.00
41.24


ATOM
3188
OD1
ASP
457
34.382
37.925
22.163
1.00
44.36


ATOM
3189
OD2
ASP
457
35.874
36.471
23.032
1.00
50.52


ATOM
3190
C
ASP
457
34.847
33.825
19.742
2.00
27.01


ATOM
3191
O
ASP
457
34.839
32.685
20.210
1.00
31.27


ATOM
3192
N
GLN
458
34.413
34.096
18.515 
1.00
27.92


ATOM
3193
CA
GLN
458
33.883
33.044
17.632
1.00
30.33


ATOM
3194
CB
GLN
458
32.932
33.614
16.573
1.00
29.37


ATOM
3195
CG
GLN
458
31.866
34.561
17.053
1.00
32.48


ATOM
3196
CD
GLN
458
30.514
33.939
16.989
1.00
33.02


ATOM
3197
OE1
GLN
458
29.750
33.981
17.947
1.00
41.92


ATOM
3198
NE2
GLN
458
30.212
13.316
15.872
1.00
37.05


ATOM
3199
C
GLN
458
35.037
32.357
16.869
1.00
28.95


ATOM
3200
O
GLN
458
35.049
31.133
16.719
1.00
26.34


ATOM
3201
N
LEU
459
35.982
33.158
16.368
1.00
24.82


ATOM
3202
CA
LEU
459
37.107
32.652
15.587
1.00
19.59


ATOM
3203
CB
LEU
459
37.033
33.236
14.183
1.00
17.07


ATOM
3204
CG
LEU
459
35.684
32.976
13.504
1.00
19.32


ATOM
3205
CD1
LEU
459
35.541
33.890
12.331
1.00
16.44


ATOM
3206
CD2
LEU
459
35.549
31.523
13.074
1.00
11.36


ATOM
3207
C
LEU
459
38.455
32.987
16.182
1.00
15.91


AT011
3208
O
LEU
459
39.175
33.815
15.651
1.00
14.53


ATOM
3209
N
PRO
460
38.820
32.339
17.299
1.00
16.20


ATOM
3210
CD
PRO
460
38.042
31.315
18.012
1.00
17.21


ATOM
3211
CA
PRO
460
40.106
32.589
17.960
1.00
15.73


ATOM
3212
CB
PRO
460
40.133
31.541
19.086
1.00
17.01


ATOM
3213
CG
PRO
460
19.123
30.494
18.542
1.00
17.80


ATOM
3214 
C
PRO
460
41.257
32.386
17.008
1.00
16.53


ATOM
3215
O
PRO
460
41.079
31.758
15.967
1.00
22.97


ATOM
3216
N
PRO
461
42.426
32.982
17.302
1.00
16.43


ATOM
3217 
CD
PRO
461
42.687
33.873
18.151
1.00
16.11


ATOM
3218
CA
PRO
461
43.615
32.858
16.455
1.00
19.04


ATOM
3219
CB
PRO
461
44.550
33.938
17.011
1.00
17.90


ATOM
3220
CG
PRO
461
44.190
33.962
18.457
1.00
17.10


ATOM
3221
C
PRO
461
44.217
31.470
16.624
1.00
22.01


ATOM
3222
O
PRO
461
43.757
30.676
17.448
1.00
25.54


ATOM
3223
N
GLU
462
45.247
31.169
15.856
1.00
25.14


ATOM
3224
CA
GLU
462
45.888
29.877
15.958
1.00
28.39


ATOM
3225
CB
GLU
462
46.625
29.560
14.674
1.00
22.97


ATOM
3226
CO
GLU
462
45.675
29.090
13.527
1.00
21.83


ATOM
3227
CD
GLU
462
46.320
28.834
12.295
1.00
25.80


ATOM
3228
OE1
GLU
462
47.571
28.780
12.227
1.00
29.20


ATOM
3229
OE2
GLU
462
45.562
28.693
11.318
1.00
20.77


ATOM
3230
C
GLU
462
46.780
29.678
17.181
1.00
33.43


ATOM
3231
O
GLU
462
46.989
28.533
17.586
1.00
35.01


ATOM
3232
N
THR
463
47.307
30.775
17.745
1.00
37.95


ATOM
3233
CA
THR
463
48.170
30.767
18.946
1.00
40.65


ATOM
3234
CB
THR
463
49.674
30.861
18.635
1.00
40.48


ATOM
3235
CG1
THR
463
49.945
30.372
17.321
1.00
44.41


ATOM
3236
CG2
THR
463
50.464
30.089
19.571
1.00
40.34


ATOM
3237
C
THR
463
47.920
32.088
19.616
1.00
42.47


ATOM
3238
O
THR
463
47.497
33.022
18.952
1.00
41.83


ATOM
3239
N
THR
464
48.331
32.210
20.874
1.00
48.42


ATOM
3240
CA
THR
464
48.155
33.457
21.622
1.00
55.33


ATOM
3241
CH
THR
464
47.453
33.204
22.959
1.00
57.02


ATOM
3242
OG1
THR
464
48.099
32.118
23.633
1.00
62.71


ATOM
3243
OG2
THR
464
45.984 
32.855
22.730
1.00
59.94


ATOM
3244
C
THR
464
49.474 
34.195
21.879
1.00
58.07


ATOM
3245
O
THR
464
49.500
35.416
22.085
1.00
58.66


ATOM
3246
N
ASP
465
50.573 
33.453 
21.878 
1.00
61.40


ATOM
3247
CA
ASP
465
51.881
34.065
22.091
1.00
65.65


ATOM
3248
CB
ASP
465
52.843
33.061
22.731
1.00
66.43


ATOM
3249
CG
ASP
465
52.793
31.700
22.069
1.00
64.17


ATOM
3250
OD1
ASP 
465
52.245
30.777
22.709
1.00
61.40


ATOM 
3251
OD2
ASP 
465
53.302
31.556
20.929
1.00
62.59


ATOM
3252
C
ASP 
465
52.431
34.573
20.757
1.00
66.66


ATOM
3253 
O
ASP
465
53.641
34.569
20.518
1.00
70.16


ATOM
3254 
N
GLU
466
51.520
35.002
19.893
1.00
64.93


ATOM 
3255 
CA 
GLU 
466
51.851
35.511
18.577
1.00
60.06


ATOM 
3256 
CB 
GLU 
466
51.574
34.444
17.528
1.00
64.82


ATOM 
3257 
CG
GLU
456
52.657
33.415
17.372
1.00
71.79


ATOM 
3258
CD 
GLU 
466
53.441
33.627
16.098
1.00
76.80


ATOM
3259 
OE1
GLU 
466
52.797
33.726
15.024
1.00
78.10


ATOM 
3260
OE2
GLU 
466
54.691
33.703
16.173
1.00
79.01


ATOM 
3261 
C
GLU 
466
50.918
36.674
18.332
1.00
56.09


ATOM 
3262 
O
GLU 
466
49.742
36.607
18.684
1.00
56.03


ATOM 
3263 
N
PRO 
467
51.447
37.799
17.831
1.00
51.07


ATOM 
3254
CD
PRO
467
52.847
38.171
17.597
1.00
49.21


ATOM 
3265
CA 
PRO 
467
50.566
38.933
17.572
1.00
46.48


ATOM 
3266
CB
PRO 
467
51.486
39.931
16.858
1.00
48.89


ATOM 
3267 
CG
PRO
467
52.701
39.128
16.465
1.00
47.91


ATOM 
3268 
C
PRO
467
49.408
38.481
16.695
1.00
44.45


ATOM
3269
O
PRO 
467
49.600
37.737
15.721
1.00
42.21


ATOM
3270
N
LEU 
468
48.212
38.924
17.059
1.00
40.59


ATOM
3271
CA
LEU
468
46.995
38.561
16.352
1.00
40.01


ATOM
3272
CB
LEU
468
45.839
39.431
16.837
1.00
41.89


ATOM
3273
CG
LEU
468
44.463
39.052
16.305
1.00
41.02


ATOM
3274
CD1
LEU
468
44.105
37.664
16.775
1.00
42.02


ATOM
3275
CD2
LEU
468
43.447
40.052
16.786
1.00
44.91


ATOM
3276
C
LEU
468
47.086
38.502
14.824
1.00
37.52


ATOM
3277
O
LEU
468
46.714
37.647
14.153
1.00
36.89


ATOM
3278
N
GLU
469
47.622
39.690
14.286
1.00
38.63


ATOM
3279
CA
GLU
469
47.761
39.881
12.831
1.00
36.54


ATOM
3280
CB
GLU
469
48.312
41.280
12.543
1.00
36.96


ATOM
3281
CG
GLU
469
49.822
41.402
12.774
1.00
36.18


ATOM
3282
CD
GLU
469
50.168
42.065
14.072
1.00
33.77


ATOM
3283
OE1
GLU
469
51.233
42.715
14.107
1.00
36.01


ATOM 
3284
OE2
GLU
469
49.382
41.945
15.043
1.00
30.63


ATOM
3285
C
GLU
469
48.682
38.859
12.174
1.00
35.12


ATOM
3286
O
GLU 
469
48.816
38.801
10.941
1.00
32.72


ATOM
3287 
N
LYS
470
49.357
38.106
13.033
1.00
37.81


ATOM
3288
CA 
LYS
470
50.305
37.094
12.540
1.00
36.11


ATOM 
3289
CB
LYS
470
51.646
37.391
13.271
1.00
40.29


ATOM
3290
CG
LYS
470
52.622
37.924
12.260
1.00
50.88


ATOM
3291
CD
LYS
470
53.757
36.936
12.100
1.00
59.58


ATOM
3292
CE
LYS
470
53.236
35.529
11.834
1.00
61.72


ATOM
3293
NZ 
LYS
470
53.976
34.506
12.630
1.00
64.89


ATOM
3294
C
LYS
470
49.865
35.711
13.034
1.00
36.21


ATOM
3295
O
LYS 
470
50.504
34.733
12.659
1.00
39.63


ATOM
3295
N
ALA
471
48.771
35.613
13.779
1.00
33.18


ATOM
3297
CA
ALA
471
48.284
34.310
14.182
1.00
29.06


ATOM
3298
CB
ALA
471
48.598
34.060
15.651
1.00
25.21


ATOM
3299
C
ALA
471
46.799
34.083
13.911
1.00
29.06


ATOM
3300
O
ALA
471
46.295
33.013
14.238
1.00
31.11


ATOM 
3301
N
TYR
472
46.091
35.046
13.311
1.00
26.54


ATOM
3302
CA
TYR
472
44.650
34.861
13.057
1.00
23.18


ATOM
3303
CB
TYR
472
43.999
36.124
12.507
1.00
18.72


ATOM
3304
CG
TYR
472
44.489
36.511
11.157
1.00
22.75


ATOM
3305
CD1
TYR
472
43.860
36.031
10.020
1.00
25.95


ATOM
3306 
CE1
TYR
472
44.294
36.381
8.756
1.00
27.97


ATOM
3307
CD2
TYR
472
45.575
37.365
11.003
1.00
22.21


ATOM
3308
CE2
TYR
472
46.022
37.738
9.739
1.00
26.59


ATOM
3309
CZ
TYR
472
45.372
37.233
8.609
1.00
32.17


ATOM
3310
OH
TYR
472
45.797
37.549
7.327
1.00
36.52


ATOM
3311
C
TYR
472
44.325
33.647
12.183
1.00
20.40


ATOM
3312 
O
TYR
472
45.114
33.226
11.354
1.00
22.10


ATOM
3313
N
SER
473
43.161
33.073
12.393
1.00
15.42


ATOM
3314
CA
SER
473
42.773
31.901
11.654
1.00
18.76


ATOM
3315
CB
SER
473
42.068
30.968
12.596
1.00
20.56


ATOM
3316
OG
SER
473
40.944
31.663
13.113
1.00
18.80


ATOM
3317
C
SER
473
41.843
32.190
10.482
1.00
21.56


ATOM
3318
O
SER
473
41.654
31.317
9.623
1.00
22.66


ATOM
3319
N
HIS
474
41.203
33.366
10.478
1.00
21.81


ATOM
3320
CA
HIS
474
40.269
33.739
9.405
1.00
19.11


ATOM
3321
CB
HIS
474
38.841
33.314
9.752
1.00
15.89


ATOM
3322
CG
HIS
474
38.702
31.860
10.093
1.00
12.80


ATOM
3323
CD2
HIS
474
39.069
31.170
11.192
1.00
8.32


ATOM
3324
ND1
HIS
474
38.030
30.966
9.289
1.00
17.15


ATOM
3325
CE1
HIS
474
37.981
29.793
9.880
1.00
13.99


ATOM
3326
NE2
HIS
474
38.605
29.889
11.040
1.00
16.43


ATOM
3327
C
HIS
474
40.234
35.218
9.045
1.00
20.13


ATOM
3328
O
HIS
474
40.591
36.079
9.837
1.00
22.30


ATOM
3329
N
GLN
475
39.750
35.493
7.844
1.00
22.49


ATOM
3330
CA
GLN
475
39.613
36.848
7.328
1.00
23.06


ATOM
3331
CB
GLN
475
40.571
37.061
6.155
1.00
27.55


ATOM
3332
CG
GLN
475
40.762
35.814
5.317
1.00
44.65


ATOM
3333
CD
GLN
475
41.572
36.048
4.068
1.00
53.46


ATOM
3334
OD1
GLN
475
42.346
35.175
3.640
1.00
61.88


ATOM
3335
NE2
GLN
475
41.399
37.226
3.458
1.00
53.85


ATOM
3336
C
GLN
475
38.161
37.067
6.880
1.00
20.99


ATOM
3337
O
GLN
475
37.449
36.108
6.561
1.00
19.73


ATOM
3338
N
LEU
476
37.700
38.314
6.965
1.00
23.59


ATOM
3339
CA
LEU
476
36.337
38.691
6.565
1.00
23.47


ATOM
3340
CB
LEU
476
36.004
40.117
7.035
1.00
18.61


ATOM
3341
CG
LEU
476
34.553
40.579
6.997
1.00
13.45


ATOM
3342
CD1
LEU
476
33.742
39.763
7.990
1.00
17.94


ATOM
3343
CD2
LEU
476
34.476
42.042
7.354
1.00
16.38


ATOM
3344
C
LEU
476
36.224
38.573
5.037
1.00
25.91


ATOM
3345
O
LEU
476
37.137
38.974
4.273
1.00
24.64


ATOM
3346
N
ASN
477
35.111
37.999
4.601
1.00
23.61


ATOM
3347
CA
ASN
477
34.851
37.764
3.200
1.00
25.65


ATOM
3348
CB
ASN
477
34.815
36.245
2.973
1.00
26.73


ATOM
3349
CG 
ASN
477
34.376
35.858
1.594
1.00
30.01


ATOM
3350
OD1
ASN
477
33.219
35.499
1.365
1.00
34.38


ATOM
3351
ND2
ASN
477
35.299
35.899
0.659
1.00
27.30


ATOM
3352
C
ASN
477
33.560
38.435
2.701
1.00
27.24


ATOM
3353
O
ASN
477
33.509
38.929
1.575
1.00
30.67


ATOM
3354
N
TYR
478
32.583
38.597
3.587
1.00
28.03


ATOM
3355
CA
TYR
478
31.283
39.159
3.214
1.00
26.02


ATOM
3356
CB
TYR
478
30.437
38.021
2.617
1.00
28.82


ATOM
3357
CG 
TYR
478
29.454
38.399
1.528
1.00
29.16


ATOM
3358
CD1
TYR
478
29.910
38.749
0.244
1.00
29.31


ATOM
3359
CE1
TYR
478
29.019 
39.022
−0.799
1.00
29.21


ATOM
3360
CD2
TYR
478
28.072
38.337
1.746
1.00
25.53


ATOM
3361
CE2
TYR
478
27.170
38.609
0.702
1.00
31.35


ATOM
3362
CZ
TYR
478
27.663
38.949
−0.565
1.00
28.53


ATOM
3363
OH
TYR
478
26.818
39.188
−1.609
1.00
29.12


ATOM
3364
C
TYR
478
30.536
39.751
4.435
1.00
27.26


ATOM
3365
O
TYR
478
30.816
39.412
5.582
1.00
26.91


ATOM
3366
N
ALA
479
29.592
40.642
4.163
1.00
26.82


ATOM
3367
CA
ALA
479
28.761
41.273
5.178
1.00
26.75


ATOM
3368
CB
ALA
479
29.283
42.665
5.500
1.00
26.06


ATOM
3369
C
ALA
479
27.377
41.336
4.519
1.00
25.07


ATOM
3370
O
ALA
479
27.265
41.549
3.309
1.00
28.22


ATOM
3371
N
GLU
480
26.329
41.078
5.275
1.00
24.88


ATOM
3372
CA
GLU
480
25.008
41.108
4.677
1.00
30.15


ATOM
3373
CB
GLU
480
24.750
39.764
4.005
1.00
30.81


ATOM
3374
CG
GLU
480
23.335
39.525
3.511
1.00
34.30


ATOM
3375
CD
GLU
480
23.158
38.143
2.856
1.00
37.80


ATOM
3376
OE1
GLU
480
22.025
37.848
2.398
1.00
38.54


ATOM
3377
OE2
GLU
480
24.138
37.352
2.802
1.00
38.29


ATOM
3378
C
GLU
480
23.955
41.400
5.725
1.00
31.66


ATOM
3379
O
GLU
480
23.977
40.780
6.787
1.00
34.86


ATOM
3380
N
CYS
481
23.077
42.373
5.453
1.00
32.22


ATOM
3381
CA
CYS
481
22.013
42.740
6.391
1.00
31.34


ATOM
3382
CB
CYS
481
21.725
44.221
6.334
1.00
27.71


ATOM
3383
SG
CYS
481
23.102
45.167
6.880
1.00
33.86


ATOM
3384
C
CYS
481
20.719
42.008
6.158
1.00
33.16


ATOM
3385
O
CYS
481
20.363
41.713
5.027
1.00
36.23


ATOM
3386
N
PHE
482
20.033
41.691
7.247
1.00
34.11


ATOM
3387
CA
PHE
482
18.753
41.009
7.206
1.00
30.22


ATOM
3388
CB
PHE
482
18.845
39.637
7.849
1.00
34.49


ATOM
3389
CG
PHE
482
19.608
38.641
7.023
1.00
40.80


ATOM
3390
CD1
PHE
482
20.998
38.659
6.989
1.00
42.96


ATOM
3391
CD2
PHE
482
18.937
37.683
6.265
1.00
46.84


ATOM
3392
CE1
PHE
482
21.717
37.738
6.212
1.00
44.53


ATOM
3393
CE2
PHE
482
19.646
36.751
5.478
1.00
47.79


ATOM
3394
CZ
PHE
482
21.040
36.783
5.456
1.00
46.14


ATOM
3395
C
PHE
482
17.850
41.918
7.987
1.00
30.71


ATOM
3396
O
PHE
482
18.312
42.716
8.798
1.00
33.95


ATOM
3397
N
LEU
483
16.561
41.811
7.758
1.00
27.58


ATOM
3398
CA
LEU
483
15.647
42.703
8.420
1.00
27.73


ATOM
3399
CB
LEU
483
14.738
43.377
7.394
1.00
24.99


ATOM
3400
CG
LEU
483
15.270
44.192
6.226
1.00
21.74


ATOM
3401
CD1
LEU
483
14.098
44.627
5.397
1.00
25.27


ATOM
3402
CD2
LEU
483
16.019
45.395
6.678
1.00
21.38


ATOM
3403
C
LEU
483
14.778
41.959
9.401
1.00
31.66


ATOM
3404
O
LEU
483
14.371
40.810
9.164
1.00
31.14


ATOM
3405
N
MET
484
14.447
42.645
10.481
1.00
33.44


ATOM
3406
CA
MET
484
13.585
42.068
11.479
1.00
36.28


ATOM
3407
CB
MET
484
13.973
42.576
12.865
1.00
36.13


ATOM
3408
CG
MET
484
15.308
42.089
13.352
1.00
38.45


ATOM
3409
SD
MET
484
15.491
42.483
15.082
1.00
45.99


ATOM
3410
CE
MET
484
16.389
43.963
15.012
1.00
41.27


ATOM
3411
C
MET
484
12.132
42.427
11.152
1.00
38.11


ATOM
3412
O
MET
484
11.852
43.387
10.416
1.00
41.32


ATOM
3413
N
GLN
485
11.219
41.624
11.680
1.00
42.45


ATOM
3414
CA
GLN
485
9.782
41.819
11.511
1.00
46.46


ATOM
3415
CB
GLN
485
9.037
40.519
11.822
1.00
47.26


ATOM
3416
CG
GLN
485
9.396
39.376
10.884
1.00
48.83


ATOM
3417
CD
GLN
485
8.697
38.093
11.257
1.00
51.68


ATOM
3418
OE1
GLN
485
9.325
37.185
11.774
1.00
56.20


ATOM
3419
NE2
GLN
485
7.386
38.015
11.014
1.00
54.56


ATOM
3420
C
GLN
485
9.303
42.928
12.446
1.00
46.51


ATOM
3421
O
GLN
485
10.050
43.400
13.307
1.00
43.94


ATOM
34.22
N
ASP
486
8.054
43.344
12.278
1.00
48.98


ATOM
3423
CA
ASP
486
7.502
44.417
13.099
1.00
51.60


ATOM
3424
CB
ASP
486
7.163
43.889
14.498
1.00
55.79


ATOM
3425
CG
ASP
486
6.188
44.788
15.242
1.00
60.84


ATOM
3426
OD1
ASP
486
5.712
45.784
14.657
1.00
66.91


ATOM
3427
OD2
ASP
486
5.899
44.500
16.424
1.00
65.08


ATOM
3428
C
ASP
486
8.507
45.588
13.163
1.00
50.17


ATOM
3429
O
ASP
486
8.714
46.203
14.213
1.00
51.11


ATOM
3430
N
ARG
487
9.168
45.826
12.030
1.00
49.23


ATOM
3431
CA
ARG
487
10.150
46.895
11.851
1.00
50.67


ATOM
3432
CB
ARG
487
9.443
48.192
11.482
1.00
59.54


ATOM
3433
CG
ARG
487
8.846
48.250
10.104
1.00
69.48


ATOM
3434
CD
ARG
487
7.999
49.490
10.008
1.00
77.95


ATOM
3435
NE
ARG
487
7.637
49.805
8.634
1.00
90.05


ATOM
3436
CZ
ARG
487
7.217
51.006
8.243
1.00
96.14


ATOM
3437
NH1
ARG
487
6.905
51.221
6.961
1.00
99.29


ATOM
3438
NH2
ARG
487
7.108
51.995
9.138
1.00
97.66


ATOM
3439
C
ARG
487
11.067
47.204
13.017
1.00
48.25


ATOM
3440
O
ARG
487
11.190
48.369
13.405
1.00
50.28


ATOM
3441
N
ARG
488
11.721
46.198
13.580
1.00
43.30


ATOM
3442
CA
ARG
488
12.622 
46.470
14.693
1.00
44.26


ATOM
3443
CB
ARG
488
12.667
45.285
15.667
1.00
45.30


ATOM
3444
CG
ARG
488
11.324
44.941
16.242
1.00
38.00


ATOM
3445
CD
ARG
488
10.692
46.175
16.832
1.00
34.28


ATOM
3446
NE
ARG
488
9.310
45.889
17.157 
1.00
33.22


ATOM
3447
CZ
ARG
488
8.922
45.236
18.248
1.00
34.98


ATOM
3448
NH1
ARG
488
9.815
44.815
19.131
1.00
34.60


ATOM
3449
NH2
ARG
488
7.641
44.928
18.422
1.00
38.53


ATOM
3450
C
ARG
488
14.037
46.883
14.252
1.00
44.49


ATOM
3451
O
ARG
488
14.851
47.349
15.075
1.00
44.38


ATOM
3452 
N
GLY
489
14.323
46.738
12.958 
1.00
40.82


ATOM
3453
CA
GLY
489
15.634 
47.110
12.461
1.00
38.10


ATOM
3454 
C
GLY
489
16.300
46.037
11.622
1.00
37.57


ATOM
3455
O
GLY
489
15.618
45.144
11.094
1.00
36.28


ATOM
3456 
N
THR 
490
17.628 
46.1251
1.493 
1.00
35.19


ATOM
3457
CA
THR
490
18.379
45.152
10.711
1.00
30.90


ATOM
3458
CB
THR
490
18.837
45.747
9.346
1.00
29.73


ATOM
3459
CG1
THR
490
20.169
46.257
9.440
1.00
33.88


ATOM
3460
CG2
THR
490
17.924
46.870
8.941
1.00
24.06


ATOM
3461
C
THR
490
19.566
44.566
11.478
1.00
31.16


ATOM
3462
O
THR
490
20.287
45.296
12.156
1.00
31.36


ATOM
3463
N
ILE
491
19.705
43.235
11.423
1.00
28.86


ATOM
3464
CA
ILE
491
20.802
42.496
12.073
1.00
26.73


ATOM
3465
CB
ILE
491
20.320
41.170
12.803
1.00
26.17


ATOM
3466
CG2
ILE
491
20.602
41.207
14.292
1.00
29.86


ATOM
3467
CG1
ILE
491
18.854
40.882
12.535
1.00
27.37


ATOM
3468
CD1
ILE
491
18.659
39.784
11.547
1.00
32.39


ATOM
3469
C
ILE
491
21.786
42.045
10.992
1.00
24.72


ATOM
3470
O
ILE 
491
21.402
41.341
10.055
1.00
27.21


ATOM
3471
N
PRO
492
23.041
42.490
11.061
1.00
23.25


ATOM
3472
CD
PRO 
492
23.497
43.732
11.703
1.00
20.04


ATOM
3473
CA
PRO
492
24.005
42.064
10.036
1.00
24.76


ATOM
3474
CB
PRO
492
25.050
43.171
10.070
1.00
23.01


ATOM
3475
CG
PRO
492
24.301
44.338
10.611
1.00
24.54


ATOM
3476
C
PRO
492
24.634
40.677
10.326
1.00
27.40


ATOM
3477
O
PRO
492
24.626
40.210
11.476
1.00
27.66


ATOM
3478
N
PHE
493
25.124
40.027
9.263
1.00
30.29


ATOM
3479
CA
PHE
493
25.775
38.701
9.293
1.00
30.16


ATOM
3480 
CB
PHE
493
25.033
37.677
8.406
1.00
36.53


ATOM
3481
CG
PHE
493
23.702
37.212
8.925
1.00
45.55


ATOM
3482
CD1
PHE 
493
22.830
38.075
9.597
1.00
52.04


ATOM
3483
CD2
PHE 
493
23.279
35.916
8.660
1.00
47.34


ATOM
3484
OE1
PHE
493
21.540
37.651
9.992
1.00
52.95


ATOM
3485
CE2
PHE
493
22.007 
35.486 
9.044
1.00
51.52


ATOM
3486
C2
PHE
493
21.131
36.354
9.713
1.00
52.07


ATOM
3487
C
PHE
493
27.141
38.832
8.601
1.00
28.46


ATOM
3488
O
PHE
493
27.207
39.375
7.490
1.00
27.20


ATOM
3489
N
PHE
494
28.194
38.268 
9.193
1.00
22.47


ATOM
3490
CA
PHE
494
29.525
36.266
8.576
1.00
21.79


ATOM
3491
CB
PHE
494
30.585
38.704
9.569
1.00
24.52


ATOM
3492 
CG 
PHE
494
30.596
40.163 
9.819
1.00
31.15


ATOM
3493
CD1
PHE
494
30.974
40.682
11.056
1.00
28.30


ATOM
3494
CD2
PHE
494
30.267
41.059
8.793
1.00
33.44


ATOM
3495
CE1
PHE
494
31.028
42.043
11.265
1.00
31.41


ATOM
3496
CE2
PHE
494
30.315
42.445
8.992
1.00
29.26


ATOM
3497
CZ 
PHE
494
30.700
42.935
10.227
1.00
25.91


ATOM
3498
C
PHE
494
29.882
36.851
8.065
1.00
24.01


ATOM
3499
O
PHE
494
29.352
35.851
8.568
1.00
20.12


ATOM
3500
N
THR
495
30.753
36.786
7.057
1.00
20.49


ATOM
3501
CA
THR
495
31.220
35.533
6.467
1.00
18.98


ATOM
3502
CB
THR
495
30.712
35.369
5.053
1.00
22.01


ATOM
3503
OG1
THR
495
29.297
35.571
5.035
1.00
19.23


ATOM
3504
CG2
THR
495
31.056
33.962
4.531
1.00
19.98


ATOM
3505
C
THR
495
32.745
35.571
6.397
1.00
19.99


ATOM
3506
O
THR
495
33.314
36.519
5.857
1.00
17.46


ATOM
3507
N
TRP
496
33.403
34.527
6.893
1.00
19.16


ATOM
3508
CA
TRP
496
34.858
34.492
6.921
1.00
19.00


ATOM
3509
CB
TRP
496
35.328
34.416
8.378
1.00
19.02


ATOM
3510
CG
TRP
496
34.732
35.457
9.277
1.00
17.89


ATOM
3511
CD2
TRP
496
35.405
36.601
9.851
1.00
20.54


ATOM
3512
CE2
TRP
496
34.438
37.342
10.579
1.00
20.61


ATOM
3513
CE3
TRP
496
36.730
37.071
9.825
1.00
19.34


ATOM
3514
CD1
TRP
496
33.424
35.543
9.681
1.00
19.86


ATOM
3515
NE1
TRP
496
33.241
36.680
10.458
1.00
23.72


ATOM
3516
CZ2
TRP
496
34.756
38.525
11.263
1.00
18.67


ATOM
3517
CZ3
TRP
496
37.044
18.263
10.521
1.00
15.75


ATOM
3518
CH2
TRP 
496
36.059
38.963
11.223
1.00
12.02


ATOM
3519 
C
TRP
496
35.465
33.318
0.147
1.00
18.54


ATOM 
1520
O
TRP
496
34.789
32.321
5.914
1.00
16.59


ATOM
3521
N
THR 
497
36.729
33.459 
5.735
1.00
17.86


ATOM
3522
CA
THR 
497
37.463
32.391
5.040
1.00
20.19


ATOM
3523
CB
THR
497
37.694
32.650
3.524
1.00
19.90


ATOM
3524
OG1
THR
497
38.546
33.787
3.320
1.00
19.60


ATOM
3525
OG2
THR
497
36.390
32.884
2.835
1.00
18.46


ATOM
3526
C
THR
497
38.811
32.171
5.773
1.00
23.90


ATOM
3527
O
THR
497
39.338
33.085
6.443
1.00
24.61


ATOM
3528
N
HIS
498
39.328
30.947
5.681
1.00
20.24


ATOM
3529
CA
HIS
498
40.544
30.546
6.355
1.00
18.34


ATOM
3530
CB
HIS
498
40.721
29.034 
6.233
1.00
17.33


ATOM
3531
CG
HIS
498
41.575
28.440 
7.312
1.00
19.72


ATOM
3532
CD2
HIS
498
41.296
28.147 
8.603
1.00
17.68


ATOM
3533
ND1
HIS
498
42.889
28.069
7.112
1.00
18.83


ATOM
3534
CE1
HIS
498
43.385
27.578
8.233
1.00
18.42


ATOM
3535
NE2
HIS
498
42.438
27.615 
9.154
1.00
20.50


ATOM
3536
C
HIS
498
41.795
31.233
5.871
1.00
19.67


ATOM
3537
O
HIS
498
42.023
31.388
4.674
1.00
22.08


ATOM
3538
N
ARG 
499
42.679
31.520
6.809
1.00
21.68


ATOM
3539 
CA
ARG
499
43.937
32.177
6.475
1.00
24.21


ATOM
3540
CB
ARG
499
44.705
32.506
7.753
1.00
27.17


ATOM
3541
CG
ARG
499
45.003
31.299
8.637
1.00
33.94


ATOM
3542
CD
ARG
499
46.383
30.756
8.400
1.00
38.30


ATOM
3543
NE
ARG
499
46.458
29.344
8.771
1.00
51.54


ATOM
3544
CZ 
ARG
499
47.386
28.500
8.324
1.00
55.23


ATOM
3545
NH1
ARG
499
47.369
27.229
8.722
1.00
57.57


ATOM
3546
NH2
ARG 
499
48.322
28.920
7.473
1.00
55.32


ATOM
3547
C
ARG
499
44.813
31.328
5.556
1.00
23.51


ATOM
3548
O
ARG
499
45.787
31.816
4.999
1.00
27.69


ATOM
3549
N
SER
500
44.476
30.060
5.390
1.00
19.69


ATOM
3550
CA
SER
500
45.300
29.227
4.561
1.00
21.75


ATOM
3551
CB
SER
500
45.031
27.736
4.818
1.00
21.16


ATOM
3552
OG
SER
500
43.708
27.365
4.461
1.00
15.96


ATOM
3553
C
SER
500
45.178
29.533
3.082
1.00
25.26


ATOM
3554
O
SER
500
46.068
29.152
2.323
1.00
31.57


ATOM
3555
N
VAL
501
44.089
30.184
2.656
1.00
24.13


ATOM
3556
CA
VAL
501
43.888
30.486
1.226
1.00
21.77


ATOM
3557
CB
VAL
501
42.554
31.137
0.974
1.00
18.09


ATOM
3558
CG1
VAL
501
42.479
31.606
−0.440
1.00
15.04


ATOM
3559
CG2
VAL
501
41.437
30.158
1.276
1.00
18.35


ATOM
3560
C
VAL
501
44.976
31.359
0.599
1.00
25.52


ATOM
3561
O
VAL
501
45.155
32.518
0.963
1.00
31.84


ATOM
3562
N
ASP
502
45.666
30.800
−0.385
1.00
26.11


ATOM
3563
CA
ASP
502
46.751
31.478
−1.073
1.00
25.59


ATOM
3564
CB
ASP
502
47.673
30.432
−1.694
1.00
25.96


ATOM
3565
CG 
ASP
502
48.924
31.022
−2.302 
1.00
29.25


ATOM
3566
OD1
ASP
502
49.141
32.243
−2.177
1.00
32.80


ATOM
3567
OD2
ASP
502
49.702 
30.241
−2.904
1.00
28.44


ATOM
3568
C
ASP
502
46.153
32.319
−2.170
1.00
27.90


ATOM
3569
O
ASP
502
45.642
31.780
−3.153 
1.00
29.56


ATOM
3570
N
PHE
503
46.230
33.635
2.030
1.00
29.10


ATOM
3571
CA
PHE
503
45.691
34.514
−3.059
1.00
29.42


ATOM
3572
CB
PHE
503
45.842
35.970
−2.639
1.00
31.35


ATOM
3573
CG
PHE
503
45.414
36.927
−3.690
1.00
32.60


ATOM
3574
CD1
PHE
503
44.084
37.022
−4.043
1.00
31.44


ATOM
3575
CD2
PHE
503
46.351
37.691
−4.368
1.00
35.02


ATOM
3578
CE1
PHE
503
43.682
37.862
−5.055
1.00
34.84


ATOM
3577
CE2
PHE
503
45.965
38.535
−5.383
1.00
35.77


ATOM
3578
CZ
PHE
503
44.623
38.623
−5.733
1.00
35.90


ATOM
3579
C
PHE
503
46.367
34.296
−4.430
1.00
30.03


ATOM
3580
O
PHE
503
45.708
34.347
−5.480
1.00
30.07


ATOM
3581
N
PHE
504
41.667
34.001
−4.401
1.00
25.40


ATOM
3582
CA
PHE
504
48.459
33.792
−5.606
1.00
20.19


ATOM
3583
CB
PHE
504
49.896
34.175
−5.108
1.00
27.87


ATOM
3584
CG
PHE
504
50.033
35.605
−4.960
1.00
26.09


ATOM
3585
CD1
PHE
504
50.089
36.004
−3.635
1.00
23.60


ATOM
3565
CD2
PHE
504
49.954
36.579
−5.963
1.00
25.37


ATOM
3587
CE1
PHE
504
50.051
37.354
−3.310
1.00
26.79


ATOM
3588
CE2
PHE
504
49.914
37.927
−5.653
1.00
27.28


ATOM
3589
CZ
PHE
504
49.959
38.321
−4.323
1.00
26.34


ATOM
3590
C
PHE
504
48.421
32.462
−6.321
1.00
20.08


ATOM
3591
O
PHE
504
49.106
32.285
−7.328
1.00
19.90


ATOM
3592
N
ASN
505
47.650
31.518
−5.809
1.00
19.82


ATOM
3593
CA
ASN
505
47.581
30.208
−6.433
1.00
19.32


ATOM
3594
CB
ASN
505
46.744
30.294
−7.702
1.00
24.30


ATOM
3595
CG
ASN
505
45.284
30.542
−7.415
1.00
25.23


ATOM
3596
OD1
ASN
505
44.874
30.529
−6.261
1.00
31.04


ATOM
3597
ND2
ASN
505
44.488
30.756
−8.461
1.00
26.30


ATOM
3598
C
ASN
505
48.983
29.683
−6.756 
1.00 
20.70


ATOM
3599
O
ASN
505
49.216
29.101
−7.817
1.00
20.32


ATOM
3600
N
THR
506
49.917
29.914
−5.842
1.00
16.35


ATOM
3601
CA
THR
506
51.305
29.505
−6.010
1.00
20.86


ATOM
3602
CB
THR
506
52.150
30.067
−4.501
1.00
24.90


ATOM
3603
OG1
THR
506
51.526
31.483
−4.667
1.00
30.23


ATOM
3604
CG2
THR
506
53.640
29.820
−4.972
1.00
22.07


ATOM
3605
C
THR
506
51.514
27.973
−6.141
1.00
23.99


ATOM
3606
0
THR
506
50.138
327.197
−5.423 
1.00
27.58


ATOM
3607
N
ILE
507
52.354
27.542
−7.086
1.00
22.61


ATOM
3608
CA
ILE
507
52.684
26.128
−7.255
1.00
18.50


ATOM
3609
CB
ILE
507
52.811 
25.719
−8.720
1.00
17.29


ATOM
3610
CG2
ILE
507
53.059
24.277
−8.808
1.00
15.63


ATOM
3611
CG1
ILE
507
51.570
26.091
−9.523
1.00
20.82


ATOM
3612
CD1
ILE
507
50.307
25.413
−9.066
1.00
29.01


ATOM
3613
C
ILE
507
54.082
26.024
−6.663
1.00
22.48


ATOM
3614
O
ILE
507
55.009
26.678
−7.147
1.00
24.75


ATOM
3615
N
ASP
508
54.220
25.237
−5.598
1.00
28.69


ATOM
3616
CA
ASP
508
55.490
25.018
−4.872
1.00
29.24


ATOM
3617
CB
ASP
508
55.196
24.244
−3.576
1.00
30.26


ATOM
3618
CG
ASP
508
56.258
24.441
−2.513
1.00
30.30


ATOM
3619
OD1
ASP
508
56.151
25.441
−1.789
1.00
40.59


ATOM
3620
OD2
ASP
508
57.179
23.608
−2.368
1.00
33.88


ATOM
3621
C
ASP
508
56.497
24.218
−5.700
1.00
28.60


ATOM
3622
O
ASP
508
56.116
23.312
−6.426
1.00
31.91


ATOM
3623
N
ALA
509
57.785
24.472
−5.518
1.00
28.24


ATOM
3624
CA
ALA
509
58.805
23.750
−6.296
1.00
29.33


ATOM
3625
CB
ALA
509
60.049
24.613
−6.412
1.00
35.65


ATOM
3626
C
ALA
509
59.201
22.391
−5.788
1.00
27.56


ATOM
3627
O
ALA
509
59.779
21.599
−6.547
1.00
25.79


ATOM
3628
N
GLU
510
58.963
22.166
−4.491
1.00
27.06


ATOM
3629
CA
GLU
510
59.303
20.920
−3.783
1.00
29.89


ATOM
3630
CD
GLU
510
60.020
21.242
−2.458
1.00
38.97


ATOM
3631
CG
GLU
510
61.233
22.188
−2.502
1.00
49.84


ATOM
3632
CD
GLU
510
62.515
21.514
−2.997
1.00
58.12


ATOM
3633
OE1
GLU
510
63.358
22.221
−3.599
1.00
60.55


ATOM
3634
OE2
GLU
510
62.691
20.286
−2.779
1.00
63.36


ATOM
3635
C
GLU
510
58.076
20.055
−3.435
1.00
29.54


ATOM
3636
O
GLU
510
58.046
18.858
−3.696
1.00
30.98


ATOM
3637
N
LYS
511
57.101
20.655
−2.764
1.00
22.60


ATOM
3638
CA
LYS
511
55.905
19.944
−2.366
1.00
22.05


ATOM
3639
CB
LYS
511
55.161
20.748
−1.307
1.00
26.10


ATOM
3640
CG
LYS
511
55.963
21.228
−0.151
1.00
26.97


ATOM
3641
CD
LYS
511
55.046
21.938
0.826
1.00
27.62


ATOM
3642
CE
LYS
511
55.824
22.589
1.947
1.00
27.53


ATOM
3643
NE
LYS
511
56.428
23.877
1.516
1.00
38.15


ATOM
3644
C
LYS
511
54.900
19.680
−3.493
1.00
20.67


ATOM
3645
O
LYS
511
54.972
20.269
−4.573
1.00
17.60


ATOM
3646
N
ILE
512
53.932
18.819
−3.180
1.00
19.36


ATOM
3647
CA
ILE
512
52.829
18.484
−4.068
1.00
20.42


ATOM
3648
CB
ILE
512
52.170
17.166
−3.668
1.00
16.67


ATOM
3649
CG2
ILE
512
50.863
16.971
−4.416
1.00
9.97


ATOM
3650
CG1
ILE
512
53.148
16.022
−3.921
1.00
12.77


ATOM
3651
CD1
ILE
512
52.728
14.748
−3.293
1.00
12.13


ATOM
3652
C
ILE
512
51.860
19.607
−3.748
1.00
25.62


ATOM
3653
O
ILE
512
51.643
19.919
−2.569
1.00
26.02


ATOM
3654
N
THR
513
51.299
20.224
−4.781
1.00
23.63


ATOM
3655
CA
THR
513
50.398
21.344
−4.594
1.00
21.04


ATOM
3656
CB
THR
513
50.929
22.537
−5.378
1.00
21.80


ATOM
3657
OG1
THR
513
52.250
22.847
−4.910
1.00
19.60


ATOM
3658
CG2
THR
513
50.041 
23.733
−5.217
1.00
16.11


ATOM
3659
C
THR
513
48.980
21.046
−5.013
1.00
21.44


ATOM
3660
O
THR
513
48.760
20.534
−6.089
1.00
22.73


ATOM
3661
N
GLN
514
48.024
21.302
−4.125
1.00
24.53


ATOM
3662
CA
GLN
514
46.605
21.088
−4.432
1.00
24.32


ATOM
3663
CB
GLN
514
45.826
20.522
−3.230
1.00
19.75


ATOM
3664
CG
GLN
514
46.008
19.039
−2.972
1.00
16.42


ATOM
3665
CD
GLN 
514
44.859 
18.416
−2.171
1.00
17.95


ATOM
3666
OE1
GLN
514
44.379
17.318
−2.501
1.00
13.78


ATOM
3667
NE2
GLN
514
44.395
19.121
−1.141
1.00
10.87


ATOM
3668
C
GLN
514
46.004
22.441
−4.799
1.00
22.49


ATOM
3669
O
GLN
514
46.181
23.397
−4.041
1.00
25.77


ATOM
3670
N
LEU
515
45.357
22.522
−5.970
1.00
20.22


ATOM
3671
CA
LEU
515
44.694
23.734
−6.442
1.00
19.38


ATOM
3672
CB
LEU
515
45.116
24.108
−7.883
1.00
24.66


ATOM
3673
CG
LEU
515
44.498
25.381
−8.514
1.00
19.43


ATOM
3674 
CD1
LEU
515
44.854
26.618
−7.735
1.00
17.74


ATOM
3675
CD2
LEU
515
44.941
25.544
−9.931
1.00
20.58


ATOM
3676
C
LEU
515
43.197
21.474
−6.393
1.00
21.82


ATOM
3677
O
LEU
515
42.670
22.664
−7.172
1.00
20.91


ATOM
3678
N
PRO
516
42.509
24.057
−5.391
1.00
23.18


ATOM
3679
CD
PRO
516
43.000
24.926
−4.299
1.00
20.43


ATOM
3660
CA
PRO
516
41.062
23.849
−5.292
1.00
20.71


ATOM
3681
CB
PRO
516
40.677
24.713
−4.086
1.00
22.88


ATOM
3682
CG
PRO
516
41.941
24.755
−3.249
1.00
18.38


ATOM
3683
C
PRO
516
40.457
24.382
−6.600
1.00
21.60


ATOM
3684
O
PRO
516
40.820
25.459
−7.105
1.00
20.78


ATOM
3685
N
VAL
517
39.550
23.624
−7.174
1.00
19.37


ATOM
3686
CA
VAL
517
38.964
24.045
−8.431
1.00
19.42


ATOM
3687
CB
VAL
517
38.135
22.859
−9.010
1.00
17.07


ATOM
3688
CG1
VAL
517
36.717
22.848
−8.468
1.00
18.76


ATOM
3689
CG2
VAL
517
38.203
22.842
−10.505
1.00
19.36


ATOM
3690
C
VAL
517
38.206
25.410 
−8.324
1.00
20.59


ATOM
3691
O
VAL
517
38.076
26.146
−9.307
1.00
16.82


ATOM
3692
N
VAL
518
37.813
25.755
−7.100
1.00
23.40


ATOM
3693
CA
VAL
518
37.115
27.053
−6.842
1.00
19.17


ATOM
3694
CB
VAL
518
36.353
27.093
−5.486
1.00
10.97


ATOM
3695
CG1
VAL
518
35.202
26.153
−5.513
1.00
7.06


ATOM
3696 
CG2
VAL
518
37.302
26.810
−4.333
1.00
9.27


ATOM
3697
C
VAL
518
38.049
28.258
−6.877
1.00
21.48


ATOM
3698
O
VAL
516
37.595
29.399
−6.689
1.00
23.23


ATOM
3699
N
LYS
519
39.342
28.022
−7.089
1.00
8.73


ATOM
3700
CA
LYS
519
40.297
29.124
−7.173
1.00
19.19


ATOM
3701
CB
LYS
519
41.681
28.685
−6.676
1.00
21.90


ATOM
3702
CG
LYS
519
41.673
28.268
−5.224
1.00
21.02


ATOM
3703
CD
LYS
519
41.574
29.452
−4.322
1.00
12.82


ATOM
3704
CE
LYS
519
42.966
29.886
−4.023
1.00
12.46


ATOM
3705
NE
LYS
519
42.930
31.325
−4.032
1.00
21.04


ATOM
3706
C
LYS
519
40.376
29.653
−8.608
1.00
19.96


ATOM
3707
O
LYS
519
41.147
30.566
−8.897
1.00
23.17


ATOM
3708
N
ALA
520
39.642
29.016
−9.517
1.00
21.32


ATOM
3703
CA
ALA
520
39.572
29.439
−10.916
1.00
24.50


ATOM
3710
CB
ALA
520
38.624
28.531
−11.700
1.00
18.52


ATOM
3711
C
ALA
520
39.008
30.844
−10.906
1.00
28.46


ATOM
3712
O
ALA
520
38.227
31.196
−10.012
1.00
31.25


ATOM
3713
N
TYR
521
39.373
31.649
−11.893
1.00
31.66


ATOM
3714
CA
TYR
521
38.844
32.996
−11.943
1.00
30.02


ATOM
3715
CB
TYR
521
39.943
33.981
−12.295
1.00
33.11


ATOM
3716
CG
TYR
521
40.519
33.781
−13.660
1.00
39.15


ATOM
3717
CD1
TYR
521
39.878
34.304
−14.777
1.00
39.69


ATOM
3718
CE1
TYR
521
40.423
34.180
−16.043
1.00
44.05


ATOM
3719
CD2
TYR
521
41.733
33.115
−13.840
1.00
44.01


ATOM
3720
CE2
TYR
521
42.299
32.982
−15.116
1.00
44.87


ATOM
3721
CZ
TYR
521
41.635
33.527
−16.213
1.00
44.96


ATOM
3722
OH
TYR
521
42.177
33.480
−17.480
1.00
46.99


ATOM
3723
C
TYR
521
37.663
33.115
−12.897
1.00
29.31


ATOM
3724
O
TYR
521
36.953
34.115
−12.892
1.00
30.01


ATOM
3725
N
ALA
522
37.405
32.058
−13.654
1.00
27.46


ATOM
3726
CA
ALA
522
36.321
32.062
−14.626
1.00
25.98


ATOM
3727
CB
ALA
522
36.836
32.608
−15.952
1.00
25.45


ATOM
3728
C
ALA
522
35.783
30.654
−14.814
1.00
24.28


ATOM
3729
O
ALA
522
36.520
29.703
−14.620
1.00
28.55


ATOM
3730
N
LEU
523
34.501
30.524
−15.152
1.00
22.39


ATOM
3731
CA
LEU
523
33.873
29.215
−15.368
1.00
25.19


ATOM
3732
CB
LEU
523
32.917
28.811
−14.244
1.00
22.10


ATOM
3733
CG
LEU
523
33.289
28.143
−12.941
1.00
21.99


ATOM
3734
CD1 
LEU
523
31.973
27.665
−12.307
1.00
17.94


ATOM
3735
CG2
LEU
523
34.212
26.962
−13.171
1.00
21.88


ATOM
3736
C
LEU
523
33.028
29.278
−16.617
1.00
29.42


ATOM
3737
O
LEU
523
32.535
30.348
−16.958
1.00
34.90


ATOM
3738
N
SER
524
32.802
28.133
−17.258
1.00
30.06


ATOM
3739
CA
SER
524
31.998
28.085
18.463
1.00
31.24


ATOM
3740
CB
SER
524
32.529
27.015
−19.437
1.00
30.18


ATOM
3741
OG
SER
524
31.702
25.859
−19.512
1.00
33.88


ATOM
3742
C
SER
524
30.558
27.827
−18.055
1.00
34.56


ATOM
3743
0
SER
524
30.298
27.349
−16.955
1.00
35.42


ATOM
3744
N
SER
525
29.630
28.145
−18.953
1.00
40.50


ATOM
3745
CA
SEE
525
28.186
27.978
−18.745
1.00
41.55


ATOM
3746
CB
SER
525
27.443
28.284
−20.053
1.00
44.75


ATOM
3747
OG
SER
525
28.180
29.192
20.862
1.00
50.22


ATOM
3748
C
SER
525
27.793
26.570
−18.310
1.00
41.55


ATOM
3749
O
SER
525
26.793
26.386
−17.615
1.00
41.77


ATOM
3750
N
GLY
526
28.565
25.579
−18.748
1.00
41.99


ATOM
3751
CA
GLY
526
28.251
24.200
−18.427
1.00
42.33


ATOM
3752
C
GLY
526
28.766
23.641
−17.118
1.00
39.74


ATOM
3753
O
GLY
526
28.651
22.443
−16.887
1.00
41.33


ATOM
3754
N
ALA
527
29.321
24.463
−16.262
1.00
35.00


ATOM
3755
CA
ALA
527
29.840
24.010
−15.005
1.00
31.00


ATOM
3756
CH
ALA
527
31.319
24.130
−15.004
1.00
25.11


ATOM
3757
C
ALA
527
29.241
24.865
−13.917
1.00
32.0/


ATOM
3758
O
ALA
527
28.887
26.013
−14.153
1.00
35.83


ATOM
3759
N
SER
528
29.079
24.303
−12.732
1.00
31.08


ATOM
3760
CA
SER
528
28.546
25.076
−11.624
1.00
31.31


ATOM
3761
CB
SER
528
27.040
24.870
−11.515
1.00
30.58


ATOM
3762
OG
SER
528
26.734
23.533
−11.161
1.00
36.73


ATOM
3763
C
SER
528
29.232
24.686
−10.315
1.00
29.29


ATOM
3764
O
SER
528
29.679
23.545
−10.159
1.00
26.49


ATOM
3765
N
ILE
529
29.409
25.659
−9.424
1.00
27.83


ATOM
3766
CA
ILE
529
30.005
25.375
−8.130
1.00
27.64


ATOM
3767
CB
ILE
529
30.721
26.596
−7.493
1.00
27.04


ATOM
3768
CG2 
ILE
529
31.322
26.216
−6.134
1.00
18.53


ATOM
3769
CG1 
ILE
529
31.846
27.094
−8.415
1.00
19.40


ATOM
3770
CD1 
ILE
529
32.895
26.065
−8.767
1.00
21.82


ATOM
3771
C
ILE
529
28.834
24.871
−7.275
1.00
30.57


ATOM
3772
O
ILE
529
27.726
25.411
−7.288
1.00
32.70


ATOM
3773
N
ILE
530
29.084
23.801
−6.556
1.00
31.83


ATOM
3774
CA
ILE
530
28.059
23.163
−5.786
1.00
31.82


ATOM
3775
CB
ILE
530
27.571
21.955
−6.653
1.00
32.98


ATOM
3776
CG2 
ILE
530
27.538
20.628
−5.926
1.00
32.68


ATOM
3777
CG1 
ILE
530
26.272
22.355
−7.338
1.00
39.74


ATOM
3778
CD1
ILE
530
25.682
21.281
−8.215
1.00
51.04


ATOM
3779
C
ILE
530
28.594
22.862
−4.382
1.00
33.34


ATOM
3780
O
ILE
530
29.791
23.012
−4.129
1.00
34.98


ATOM
3781
N
GLU
531
27.705
22.578
−3.441
1.00
31.94


ATOM
3782
CA
GLU
531
28.123
22.303
−2.083
1.00
34.44


ATOM
3783
CB
GLU
531
26.929
22.278
−1.159
1.00
45.98


ATOM
3784
CG
GLU
531
26.914
23.434
−0.196
1.00
66.36


ATOM
3785
CD
GLU
531
26.232
23.083
1.115
1.00
77.90


ATOM
3786
OE
1 GLU
531
24.979
22.972
1.130
1.00
81.37


ATOM
3787
OE2
GLU
531
26.962
22.911
2.124
1.00
82.42


ATOM
3788
C
GLU
531
28.895
21.012
−1.933
1.00
32.72


ATOM
3789
O
GLU
531
28.470
19.961
−2.401
1.00
29.66


ATOM
3790
N
GLY
532
30.021
21.093
−1.232
1.00
30.18


ATOM
3791
CA
GLY
532
30.846
19.927
−1.030
1.00
27.98


ATOM
3792
C
GLY
532
30.138
18.922
−0.153
1.00
29.77


ATOM
3793
O
GLY
532
29.254
19.277
0.632
1.00
29.92


ATOM
3794
N
PRO
533
30.529
17.651
−0.251
1.00
28.01


ATOM
3795
CD 
PRO
533
31.657
17.234
1.095
1.00
26.16


ATOM
3796
CA
PRO
533
29.991
16.517
0.499
1.00
28.35


ATOM
3797
CB
PRO
533
30.744
15.341
−0.105
1.00
30.57


ATOM
3798
CG
PRO
533
32.064
15.941
−0.451
1.00
31.83


ATOM
3799
C
PRO
533
30.261
16.645
2.000
1.00
28.68


ATOM
3800
O
PRO
533
29.501
16.132
2.846
1.00
30.87


ATOM
3801
N
GLY
534
31.365
17.301
2.333
1.00
26.38


ATOM
3802
CA
GLY
534
31.669
17.488
3.734
1.00
22.29


ATOM
3803
C
GLY
534
33.105
17.254
4.099
1.00
22.73


ATOM
3804
O
GLY
534
33.609
17.901
5.014
1.00
24.94


ATOM
3805
N
PHE
535
33.772
16.350
3.385
1.00
20.12


ATOM
3806
CA
PHE
535
35.165
16.021
3.690
1.00
18.54


ATOM
3807
CD
PHE
535
35.314
14.500
3.811
1.00
15.96


ATOM
3808
CG
PHE
535
34.747
13.766
2.642
1.00
18.55


ATOM
3809
CE1
PHE
535
35.480
13.833
1.461
1.00
17.25


ATOM
3810
CD2
PHE
535
33.434
13.320
2.667
1.00
15.57


ATOM
3811
CE1
PHE
535
34.904
13.080
0.323
1.00
16.51


ATOM
3812
CE2
PHE
535
32.853
12.764
1.528
1.00
17.82


ATOM
3813
CZ
PHE
535
33.588
12.647
0.357
1.00
13.09


ATOM
3814
C
PHE
535
36.195
16.550
2.686
1.00
18.37


ATOM
3815
O
PHE
535
37.365
16.192
2.771
1.00
18.67


ATOM
3816
N
THR
536
35.797
17.366
1.717
1.00
17.09


ATOM
3817
CA
THR
536
36.803
17.850
0.793
1.00
20.39


ATOM
3818
CB
THR
536
36.269
17.966
−0.610
1.00
19.96


ATOM
3819
CG1
THR
536
35.193
18.909
−0.632
1.00
17.87


ATOM
3820
CG2
THR
536
35.820
16.617
−1.094
1.00
19.15


ATOM
3821
C
THR
536
37.412
19.165
1.262
1.00
23.00


ATOM
3822
O
THR
536
37.941
19.960
0.491
1.00
24.82


ATOM
3823
N
GLY
537
37.357
19.402
2.551
1.00
27.76


ATOM
3824
CA
GLY
537
37.947
20.616
3.033
1.00
33.89


ATOM
3825
C
GLY
537
37.002
21.709
2.752
1.00
33.32


ATOM
3826
O
GLY
537
35.911
21.463
2.287
1.00
38.06


ATOM
3827
N
GLY
538
37.449
22.924
2.980
1.00
37.93


ATOM
3828
CA
GLY
538
36.582
24.038
2.771
1.00
42.84


ATOM
3829
C
GLY
538
35.777
23.873
1.519
1.00
47.29


ATOM
3830
O
GLY
538
34.558
24.06
51.468
1.00
54.74


ATOM
3831
N
ASP
539
36.477
23.366
0.535
1.00
45.55


ATOM
3832
CA
ASP
539
35.907
23.168
−0.756
1.00
41.92


ATOM
3833
CB
ASP
539
36.785
22.204
−1.574
1.00
45.21


ATOM
3834
CG
ASP
539
37.857
22.920
−2.353
1.00
49.53


ATOM
3835
OD1
ASP
539
38.701
23.577
−1.693
1.00
44.03


ATOM
3836
OD2
ASP
539
37.835
22.831
−3.616
1.00
51.70


ATOM
3837
C
ASP
539
34.450
22.797
−0.928
1.00
34.91


ATOM
3838
O
ASP
539
33.806
22.129
−0.116
1.00
26.81


ATOM
3839
N
LEU
540
33.969
23.372
−2.011
1.00
29.82


ATOM
3840
CA
LEU
540
32.688
23.155
−2.585
1.00
27.20


ATOM
3841
CB
LEU
540
32.005
24.485
−2.857
1.00
24.69


ATOM
3842
CG
LEU
540
31.540
25.134
−1.561
1.00
20.73


ATOM
3843
CD1
LEU
540
30.836
26.432
−1.858
1.00
25.75


ATOM
3844
CD2
LEU
540
30.620
24.208
−0.826
1.00
15.49


ATOM
3845
C
LEU
540
33.270
22.506
−3.863
1.00
25.13


ATOM
3846
O
LEU
540
34.456
22.645
−4.147
1.00
22.50


ATOM
3847
N
LEU
541
32.488
21.736
−4.587
1.00
26.66


ATOM
3848
CA
LEU
541
33.029
21.059
−5.759
1.00
29.40


ATOM
3849
CB
LEU
541
32.562
19.590
−5.753
1.00
24.79


ATOM
3850
CG
LEU
541
32.965
18.655
−4.619
1.00
19.38


ATOM
3851
CD1
LEU
541
32.132
17.434
−4.653
1.00
23.37


ATOM
3852
CD2
LEU
541
34.394
18.273
−4.756
1.00
26.40


ATOM
3853
C
LEU
541
32.437
21.707
−6.967
1.00
31.74


ATOM
3854
O
LEU
541
31.630
22.914
−6.830
1.00
35.14


ATOM
3855
N
PHE
542
32.874
21.319
−8.156
1.00
33.03


ATOM
3856
CA
PHE
542
32.165
21.827
−9.305
1.00
34.85


ATOM
3857
CB
PHE
542
32.946
22.894
−10.101
1.00
41.04


ATOM
3858
CG
PHE
542
33.556
22.451
−11.401
1.00
41.46


ATOM
3859
CD1
PHE
542
34.706
23.080
−11.832
1.00
43.22


ATOM
3860
CD2
PHE
542
33.007
21.453
−12.192
1.00
43.55


ATOM
3061
OE1
PHE
542
35.299
22.725
−13.010
1.00
50.04


ATOM
3862
CE2
PHE
542
33.583
21.080
−13.372
1.00
51.19


ATOM
3863
CE
PHE
542
34.740
21.715
−13.791
1.00
54.39


ATOM
3864
C
PHE
542
31.563
20.654
−10.066
1.00
35.15


ATOM
3865
O
PHE
542
32.207
19.597
−10.215
1.00
34.08


ATOM
3666
N
LEU
543
30.273
20.786
−10.371
1.00
12.50


ATOM
3867
CA
LEU
543
29.531
19.770
−11.111
1.00
31.66


ATOM
3868
CB
LEU
543
28.057
19.692
−10.650
1.00
29.24


ATOM
3869
CG
LEU
543
27.107
18.714
11.379
1.00
31.50


ATOM
3870
CD1
LEU
543
27.411
17.275
−11.030
1.00
30.64


ATOM
3871
CD2
LEU
543
25.663
19.008
−11.049
1.00
31.69


ATOM
3872
C
LEU
543
29.610
20.159
−12.587
1.00
29.13


ATOM
3873
O
LEU
543
29.603
21.340
−12.933
1.00
23.01


ATOM
3874
N
LYS
544
29.727
19.165
−13.455
1.00
32.67


ATOM
3875 
CA
LYS
544
29.813
19.442
−14.876
1.00
36.80


ATOM
3876
CB
LYS
544
31.056
18.803
−15.476
1.00
37.11


ATOM
3677
CG
LYS
544
31.272
19.198
−16.904
1.00
37.33


ATOM
3878
CD
LYS
544
32.647
18.823
−17.345
1.00
42.84


ATOM
3879
CE
LYS
544
33.093
17.482
−16.791
1.00
40.97


ATOM
3880
NZ
LYS
544
13.958
17.669
−15.599
1.00
48.30


ATOM
3881
C
LYS
544
28.579
18.979
−15.605
1.00
36.90


ATOM
3882
O
LYS
544
28.158
17.827
−15.449
1.00
32.22


ATOM
3883
N
GLU
545
27.993
19.919
−16.352
1.00
40.67


ATOM
3884
CA
GLU
545
29.786
19.708
−17.153
1.00
49.67


ATOM
3885
CB
GLU
545
25.803
20.872
−16.986
1.00
57.26


ATOM
3886
CG
GLU
545
26.062
21.808
−15.801
1.00
70.57


ATOM
3887
CD
GLU
545
25.347
21.393
−14.524
1.00
79.49


ATOM
3808
OE1
GLU
545
24.824
20.253
−14.461
1.00
82.86


ATOM
3889
OE2
GLU
545
25.300
22.223
−13.561
1.00
84.89


ATOM
3890
C
GLU
545
27.132
19.591
−18.652
1.00
49.21


ATOM
3891
O
GLU
545
26.745
18.634
−19.318
1.00
47.69


ATOM
3892
N
SER
546
27.831
20.593
−19.176
1.00
52.91


ATOM
3893
CA
SER
546
28.236
20.626
−20.585
1.00
56.07


ATOM
3894
CB
SER
546
27.941
21.863
−21.289
1.00
59.19


ATOM
3895
OG
SER
546
26.228
21.789
−21.462
1.00
58.56


ATOM
3896
C
SER
546
29.760
20.718
−20.596
1.00
55.58


ATOM
3897
O
SER
546
30.338
21.272
−19.659
1.00
56.91


ATOM
3898
N
SER
547
30.397
20.214
−21.654
1.00
54.06


ATOM
3899
CA
SER
547
31.859
20.228
−21.759
1.00
54.75


ATOM
3900
CB
SER
547
32.336
18.833
−22.125
1.00
55.22


ATOM
3901
OG
SER
547
31.784
17.902
−21.213
1.00
58.09


ATOM
3902
C
SER
547
32.427
21.251
−22.753
1.00
53.95


ATOM
3903
O
SER
547
31.722
21.596
−23.705
1.00
58.59


ATOM
3904 
N
ASN
548
33.662
21.716
−22.544
1.00
52.76


ATOM
3905
CA
ASN
548
34.306
22.712
−23.428
1.00
51.19


ATOM
3906
CB
ASN
548
33.366
23.914
−23.633
1.00
56.75


ATOM
3907
CG
ASN
548
32.797
24.464
−22.328
1.00
58.52


ATOM
3908
OD1
ASN
548
33.076
23.955
−21.249
1.00
58.90


ATOM
3909
ND2
ASN
548
32.001
25.517
−22.431
1.00
67.62


ATOM
3910
C
ASN
548
35.720
23.222
−23.044
1.00
48.17


ATOM
3911
O
ASN
548
36.727
22.791
−23.603
1.00
46.64


ATOM
3912
N
SER
549
35.751
24.252
−22.199
1.00
47.03


ATOM
3913
CA
SER
549
36.959
24.892
−21.650
1.00
38.92


ATOM
3914
CB
SER
549
37.491
25.999
−22.547
1.00
42.82


ATOM
3915
OG
SER
549
37.544
27.249
−21.877
1.00
43.37


ATOM
3916
C
SER
549
36.313
25.450
−20.394
1.00
34.96


ATOM
3917
O
SER
549
35.966
26.625
−20.271
1.00
31.37


ATOM
3918
N
ILE
550
36.020
24.485
−19.541
1.00
32.88


ATOM
3919
CA
ILE
550
35.342
24.657
−18.291
1.00
32.30


ATOM
3920
CB
ILE
550
35.247
23.317
−17.575
1.00
31.25


ATOM
3921
CG2
ILE
550
34.300
23.433
−16.429
1.00
34.89


ATOM
3922
CG1
ILE
550
34.674
22.283
−18.542
1.00
30.40


ATOM
3923
CD1
ILE
550
34.896
20.896
−18.129
1.00
36.71


ATOM
3924
C
ILE
550
35.865
25.727
−17.364
1.00
31.36


ATOM
3925
O
ILE
550
35.151
26.673
−17.063
1.00
36.41


ATOM
3926
N
ALA
551
37.109
25.629
−16.932
1.00
28.45


ATOM
3927
CA
ALA
551
37.595
26.631
−16.020
1.00
23.43


ATOM
3928
CB
ALA
551
37.505
26.093
−14.589
1.00
21.57


ATOM
3929
C
ALA
551
38.994
27.128
−16.350
1.00
22.09


ATOM
3930
O
ALA
551
39.793
26.406
−16.951
1.00
20.34


ATOM
3931
N
LYS
552
39.260
28.387
−16.008
1.00
21.43


ATOM
3932
CA
LYS
552
40.561
28.996
−16.251
1.00
23.88


ATOM
3933
CB
LYS
552
40.452
30.215
−17.161
1.00
23.98


ATOM
3934
CG
LYS
552
39.861
29.894
−18.522
1.00
32.51


ATOM
3935
CD
LYS
552
39.797
31.113
−19.444
1.00
37.66


ATOM
3936
CE
LYS
552
38.344
31.508
−19.707
1.00
46.35


ATOM
3937
NZ
LYS
552
37.473
30.364
−20.166
1.00
51.47


ATOM
3938
C
LYS
552
41.122
29.414
−14.924
1.00
24.89


ATOM
3939
O
LYS
552
40.390
29.870
−14.049
1.00
25.99


ATOM
3940
N
PHE
553
42.435
29.291
−14.790
1.00
27.07


ATOM
3941
CA
PHE
553
43.116
29.623
−13.555
1.00
26.79


ATOM
3942
CB
PHE
553
43.630
28.346
−12.810
1.00
28.52


ATOM
3943
CG
PHE
553
42.560
27.342
−12.397
1.00
24.78


ATOM
3944
CD1
PHE
553
42.189
26.305
−13.251
1.00
25.89


ATOM
3945
CD2
PHE
553
41.967
27.407
−11.135
1.00
25.91


ATOM
3946
CE1
PHE
553
41.238
25.352
−12.853
1.00
29.14


ATOM
3947
CE2
PHE
553
41.021
26.461
−10.726
1.00
25.20


ATOM
3948
CZ
PHE
553
40.652
25.433
−11.584
1.00
24.73


ATOM
3949
C
PHE
553
44.366
30.352
−13.957
1.00
25.61


ATOM
3950
O
PHE
553
44.850
30.198
−15.065
1.00
25.20


ATOM
3951
N
LYS
554
44.874
31.171
−13.062
1.00
25.03


ATOM
3952
CA
LYS
554
46.157
31.764
−13.296
1.00
27.96


ATOM
3953
CB
LYS
554
46.126
33.275
−13.408
1.00
30.03


ATOM
3954
CG
LYS
554
47.524
33.810
−13.114
1.00
39.43


ATOM
3955
CD
LYS
554
47.787
35.200
−13.624
1.00
50.21


ATOM
3956
CE
LYS
554
49.197
35.626
−13.209
1.00
54.07


ATOM
3957
NZ
LYS
554
49.529
36.998
−13.675
1.00
56.26


ATOM
3958
C
LYS
554
46.907
31.312
−12.029
1.00
28.45


ATOM
3959
O
LYS
554
46.364
31.376
−10.913
1.00
28.90


ATOM
3960
N
VAL
555
48.106
30.771
−12.205
1.00
26.35


ATOM
3961
CA
VAL
555
48.886
30.278
−11.082
1.00
23.89


ATOM
3962
CB
VAL
555
49.143
28.753
−11.215
1.00
23.89


ATOM
3963
CG1
VAL
555
47.848
27.965
−11.005
1.00
19.80


ATOM
3964
CG2
VAL
555
49.693
28.436
−12.580
1.00
24.10


ATOM
3965
C
VAL
555
50.203
31.036
−10.957
1.00
26.91


ATOM
39.66
O
VAL
555
50.634
31.705
−11.892
1.00
29.30


ATOM
3967
N
THR
556
50.819
30.966
−9.785
1.00
27.03


ATOM
3968
CA
THR
556
52.077
31.644
−9.544
1.00
23.49


ATOM
3969
CB
THR
556
51.953
32.599
−8.367
1.00
23.49


ATOM
3970
OG1
THR
556
51.091
33.676
−6.743
1.00
24.29


ATOM
3971
OG2
THR
556
53.315
33.174
−7.982
1.00
22.99


ATOM
3972
C
THR
556
53.234
30.690
−9.289
1.00
26.69


ATOM
3973
O
THR
556
53.159
29.815
−8.420
1.00
27.95


ATOM
3974
N
LEU
557
54.317
30.872
−10.035
1.00
27.71


ATOM
3975
CA
LEU
557
55.500
30.038
−9.877
1.00
30.22


ATOM
3976
CB
LEU
557
55.827
29.295
−11.180
1.00
21.01


ATOM
3977
CG
LEU
557
54.939
28.087
−11.479
1.00
15.95


ATOM
3978
CD1
LEU
557
53.843
28.430
−12.423
1.00
12.75


ATOM
3979
CD2
LEU
557
55.766
26.986
−12.049
1.00
14.32


ATOM
3980
C
LEU
557
56.644
30.948
−9.506
1.00
36.22


ATOM
3981
O
LEU
557
56.571
32.146
−9.733
1.00
42.68


ATOM
3982
N
ASN
558
57.646
30.402
−8.834
1.00
42.11


ATOM
3983
CA
ASN
558
58.828
31.174
−8.458
1.00
43.14


ATOM
3984
CB
ASN
558
59.146
31.050
−6.950
1.00
47.42


ATOM
3985
CG
ASN
558
59.198
29.602
−6.457
1.00
51.14


ATOM
3986
OD1
ASN
558
60.280
29.070
−6.176
1.00
45.86


ATOM
3987
ND2
ASN
558
58.022
28.969
−6.316
1.00
53.80


ATOM
3988
C
ASN
558
59.952
30.628
−9.328
1.00
44.63


ATOM
3989
O
ASN
558
59.741
29.657
−10.066
1.00
46.90


ATOM
3990
N
SER
559
61.128
31.247
−9.273
1.00
43.06


ATOM
3991
CA
SER
553
62.270
30.812
−10.079
1.00
43.61


ATOM
3992
CB
SER
559
63.496
31.652
9.741
1.00
44.38


ATOM
3993
OG
SER
559
63.328
32.976
−10.226
1.00
50.82


ATOM
3994
C
SER
559
62.598
29.315
−9.984
1.00
41.12


ATOM
3995
O
SER
559
62.856
28.652
−10.995
1.00
41.23


ATOM
3996
N
ALA
560
62.598 
28.786
−8.768
1.00
39.09


ATOM
3997
CA
ALA
560
62.868
27.378
−8.580
1.00
34.53


ATOM
3998
CB
ALA
560
63.016
27.069
−7.113
1.00
37.40


ATOM
3999
C
ALA
560
61.719
26.583
−9.189
1.00
33.31


ATOM
4000
O
ALA
560
61.945
25.591
−9.869
1.00
35.43


ATOM
4001
N
ALA
561
60.489
27.052
−8.999
1.00
31.76


ATOM
4002
CA
ALA
561
59.330
26.347
−9.544
1.00
29.93


ATOM
4003
CB
ALA
561
58.064
26.850
−8.906
1.00
28.61


ATOM
4004
C
ALA
561
59.249
26.449
−11.066
1.00
30.20


ATOM
4005
O
ALA
561
58.607
25.630
−11.713
1.00
31.33


ATOM
4006
N
LEU
562
59.922
27.442
−11.638
1.00
32.60


ATOM
4007
CA
LEU
562
59.933
27.635
−13.088
1.00
34.08


ATOM
4008
CB
LEU
562
60.209
29.106
−13.438
1.00
13.88


ATOM
4009
CG
LEU
562
59.000
30.047
−13.329
1.00
34.94


ATOM
4010
CD1
LEU
562
59.424
11.495
−13.482
1.00
35.38


ATOM
4011
CD2
LEU
562
57.953
29.681
−14.373
1.00
32.01


ATOM
4012
C
LEU
562
60.899
26.703
−13.835
1.00
34.58


ATOM
4013
O
LEU
562
60.647
26.331
−14.979
1.00
33.64


ATOM
4014
N
LEU
563
61.992
26.314
−13.182
1.00
37.75


ATOM
4015
CA
LEU
563
62.990
25.406
−13.773
1.00
40.21


ATOM
4016
CB
LEU
563
64.290
25.475
−12.963
1.00
41.41


ATOM
4017
CG
LEU
563
65.333
26.561
−13.202
1.00
42.05


ATOM
4018
CD1
LEU
563
66.149
26.819
−11.939
1.00
43.00


ATOM
4019
CD2
LEU
563
66.231
26.107
−14.322
1.00
44.06


ATOM
4020
C
LEU
563
62.492
23.961
−13.691
1.00
41.90


ATOM
4021
O
LEU
563
63.112
23.034
−14.212
1.00
45.91


ATOM
4022
N
GLN
564
61.357
23.789
−13.036
1.00
41.36


ATOM
4023
CA
GLN
564
60.777
22.487
−12.774
1.00
39.60


ATOM
4024
CB
GLN
564
60.189
22.569
−11.349
1.00
43.83


ATOM
4025
CG
GLN
564
60.106
21.286
−10.543
1.00
50.18


ATOM
4026
CD
GLN
564
61.469
20.739
−10.147 
1.00
53.72


ATOM
4027
OE1
GLN
564
62.310
21.439
−9.558
1.00
55.36


ATOM
4028
NE2
GLN
564
61.690
19.470
−10.460
1.00
59.83


ATOM
4029
C
GLN
564
59.683
22.074
−13.761
1.00
35.38


ATOM
4030
O
GLN
564
59.102
22.912
−14.449
1.00
36.05


ATOM
4011
N
ARG
565
59.416
20.771
−13.818
1.00 
33.68


ATOM
4032
CA
ARG
565
58.333
20.220
−14.537
1.00
34.60


ATOM
4033
CB
ARG
565
58.830
19.257
−15.726
1.00
38.02


ATOM
4034
CG
ARG
565
59.353
19.990
−16.963
1.00
40.53


ATOM
4035
CD
ARG
565
59.021
19.276
−18.259
1.00
38.89


ATOM
4036
NE
ARG
565
58.289
20.150
−19.172
1.00
40.20


ATOM
4037
CZ
ARG
565
57.235
19.770
−19.887
1.00
42.15


ATOM
4038
NH1
ARG
565
56.630
20.617
−20.684
1.00
42.80


ATOM
4039
NH2
ARG
565
56.793
18.519
−19.821
1.00
45.49


ATOM
4040
C
ARG
565
57.386
19.528
−13.658
1.00
29.39


ATOM
4041
O
ARG
565
57.806
19.117
−12.573
1.00
26.69


ATOM
4042
N
TYR
566
56.131
19.368
−14.052
1.00
27.44


ATOM
4043
CA
TYR
566
55.125
18.807
−13.162
1.00
24.88


ATOM
4044
CB
TYR
566
54.241
19.954
−12.630
1.00
24.68


ATOM
4045
CG
TYR
566
55.022
21.022
−11.889
1.00
24.57


ATOM
4046
CD1
TYR
566
55.656
22.065
−12.580
1.00
23.18


ATOM
4047
CE1
TYR
566
56.479
22.951
−11.908
1.00
22.35


ATOM
4048
CD2
TYR
566
55.218
20.933 
−10.504
1.00
21.68


ATOM
4049
CE2
TYR
566
56.027
21.835
−9.833
1.00
23.53


ATOM
4050
CZ
TYR
566
56.657
22.845
−10.539
1.00
19.14


ATOM
4051
OH
TYR
566
57.511
23.668
−9.870
1.00
29.33


ATOM
4052
C
TYR
566
54.215
17.762
−13.760
1.00
26.96


ATOM
4053
O
TYR
566
53.827
17.845
−14.923
1.00
26.47


ATOM
4054
N
ARG
567
53.861
16.785
−12.937
1.00
28.74


ATOM
4055
CA
ARG
567
52.938
15.725
−13.318
1.00
27.05


ATOM
4056
CB
ARG
567
53.342
14.413
−12.647
1.00
25.39


ATOM
4057
CG
ARG
567
52.790
13.157
−13.292 
1.00
33.50


ATOM
4058
CD
ARG
567
53.135
11.592
−12.489
1.00
35.21


ATOM
4059
NE
ARG
567
52.052
11.476
11.599
1.00
37.84


ATOM
4060
CZ
ARG
567
52.230
10.952
−10.389
1.00
37.80


ATOM
4061
NH1
ARG
567
51.186
10.619
−9.660
1.00
36.93


ATOM
4062
NH2
ARG
567
53.443
10.783
−9.891
1.00
42.04


ATOM
4063
C
ARG
567
51.645
16.261
−12.689
1.00
29.34


ATOM
4064
O
ARG
567
51.678
16.847
−11.607
1.00
28.88


ATOM
4065
N
VAL
568
50.537
16.155
−13.406
1.00
29.48


ATOM
4066
CA
VAL
568
49.240
16.616
−12.929
1.00
23.50


ATOM
4067
CB
VAL
568
48.517
17.435
−14.054
1.00
29.72


ATOM
4068
CG1
VAL
568
47.083
17.817
−13.655
1.00
25.49


ATOM
4069
CG2
VAL
568
49.309
18.685 
−14.382
1.00
28.25


ATOM
4070
C
VAL
568
48.390
15.395
−12.545
1.00
23.91


ATOM
4071
O
VAL
568
48.400
14.367
−13.238
1.00
26.41


ATOM
4072
N
ARG
569
47.707
15.500
−11.411
1.00
22.32


ATOM
4073
CA
ARG
569
46.798
14.475
−10.887
1.00
21.06


ATOM
4074
CB
ARG
569
47.270
14.042
−9.543
1.00
19.44


ATOM
4075
CG
ARG
569
47.930
12.741
−9.372
1.00
20.01


ATOM
4076
CD
ARG
569
47.969
12.675
−7.867
1.00
16.43


ATOM
4077
NE
ARG
569
48.963
11.790
−7.329
1.00
17.92


ATOM
4078
CZ
ARG
569
49.377
11.807
−6.069
1.00
12.56


ATOM
4079
NH1
ARG
569
50.295
10.928
−5.686
1.00
8.11


ATOM
4080
NH2
ARG
569
48.885
12.683
−5.215
1.00
7.02


ATOM
4081
C
ARG
569
45.492
15.220
−10.600
1.00
22.50


ATOM
4082
0
ARG
569
45.535
16.336
−10.105
1.00
25.09


ATOM
4083
N
ILE
570
44.343
14.598
−10.799
1.00
21.96


ATOM
4084
CA
ILE
570
43.072
15.268
−10.535
1.00
21.79


ATOM
4085
CB
ILE
570
42.279
15.497
−11.871
1.00
24.30


ATOM
4086
CG2
ILE
570
40.750
15.555
−11.652
1.00
21.29


ATOM
4087
CG1
ILE
570
42.745
16.804
−12.494
1.00
21.98


ATOM
4088
CD1
ILE
570
43.373
16.637
−13.802
1.00
22.97


ATOM
4089
C
ILE
570
42.240
14.451
−9.563
1.00
19.98


ATOM
4090
O
ILE
570
42.061
13.258
−9.775
1.00
22.62


ATOM
4091
N
ARG
571
41.764
15.073
−8.484
1.00
22.31


ATOM
4092
CA
ARG
571
40.927
14.380
−7.502
1.00
19.02


ATOM
4093
CB
ARG
571
41.173
14.917
6.091
1.00
20.56


ATOM
4094
CG
ARG
571
40.276
14.283
−5.015
1.00
30.48


ATOM
4095
CD
ARG
571
41.093
13.628
−3.905
1.00
37.09


ATOM
4096
NE
ARG
571
40.302
13.065
−2.802
1.00
44.17


ATOM
4097
CZ
ARG
571
39.627
13.786
−1.896
1.00
49.87


ATOM
4098
NH1
ARG
571
39.607
15.129
−1.950
1.00
44.30


ATOM
4099
NH2
ARG
571
39.057
13.163
−0.861
1.00
47.17


ATOM
4100
C
ARG
571
39.505
14.657
−7.982
1.00
18.92


ATOM
4101
O
ARG
571
39.075
15.825
8.064
1.00
15.94


ATOM
4102
N
TYR
572
38.784
13.588
−8.316
1.00
16.89


ATOM
4103
CA
TYR
572
37.441
13.715
−8.860
1.00
14.77


ATOM
4104
CB
TYR
572
37.537
13.636
−10.385
1.00
16.10


ATOM
4105
CG
TYR
572
37.920
12.249
−10.863
1.00
19.08


ATOM
4106
CD1
TYR
572
36.942
11.366
−11.339
1.00
19.90


ATOM
4107
CE1
TYR
572
37.245
10.048
−11.669
1.00
16.26


ATOM
4108
CD2
TYR
572
39.237
11.778
−10.742
1.00
20.80


ATOM
4109
CE2
TYR
572
39.561
10.445
−11.070
1.00
22.00


ATOM
4110
CZ
TYR
572
38.551
9.582
−11.525
1.00
21.96


ATOM
4111
OH
TYR
572
38.799
8.241
−11.769
1.00
17.33


ATOM
4112
C
TYR
572
36.551
12.579
−8.398
1.00
16.70


ATOM
4113
O
TYR
572
36.994
11.674
7.706
1.00
17.05


ATOM
4114
N
ALA
573
35.298
12.634
−8.830
1.00
17.73


ATOM
4115
CA
ALA
573
34.280
11.618
−8.558
1.00
18.71


ATOM
4116
CB
ALA
573
33.439
12.013
−7.357
1.00
15.72


ATOM
4117
C
ALA
573
33.440
11.645
9.845
1.00
19.61


ATOM
4118
O
ALA
573
33.025
12.709
−10.291
1.00
21.78


ATOM
4119
N
SER
574
33.174
10.496
−10.444
1.00
20.78


ATOM
4120
CA
SER
574
32.442
10.490
−11.702
1.00
18.28


ATOM
4121
CB
SER
574
33.441
10.726
−12.839
1.00
20.54


ATOM
4222
OG
SER
574
32.924
10.279
−14.066
1.00
18.88


ATOM
4123
C
SER
574
31.695
9.201
−11.954
1.00
19.42


ATOM
4124
O
SER
574
32.129
8.135
−11.518
1.00
20.80


ATOM
4125
N
THR
575
30.594
9.292
−12.694
1.00
17.84


ATOM
4126
CA
THR
575
29.802
8.107
−13.017
1.00
20.27


ATOM
4127
CB
THR
575
28.302
8.391
−13.007
1.00
16.07


ATOM
4128
OG1
THR
575
28.007
9.424
−13.948
1.00
22.01


ATOM
4129
CG2
THR
575
27.875
8.857
−11.661
1.00
20.62


ATOM
4130
C
THR
575
30.138
7.475
−14.364
1.00
26.24


ATOM
4131
O
THR
575
29.468
6.511
−14.758
1.00
32.16


ATOM
4132
N
THR
576
31.146
8.009
−15.065
1.00
25.53


ATOM
4133
CA
THR
576
31.574
7.489
−16.365
1.00
28.39


ATOM
4134
CB
THR
576
30.923
8.210
−17.577
1.00
31.77


ATOM
4135
CG1
THR
576
30.795
9.612
−17.303
1.00
31.40


ATOM
4136
CG2
THR
576
29.604
7.570
−17.985
1.00
34.68


ATOM
4137
C
THR
576
33.029
7.746
−16.597
1.00
29.87


ATOM
4138
O
THR
576
33.623
8.601 
−15.950
1.00
34.81


ATOM
4139
N
ASN
577
33.585
7.029
−17.567
1.00
31.68


ATOM
4140
CA
ASN
577
34.965
7.234
−17.962
1.00
32.54


ATOM
4141
CB
ASN
577
35.513
6.018
−18.723
1.00
38.35


ATOM
4142
CG
ASN
577
35.575
4.757
−17.863
1.00
45.89


ATOM
4143
OD1
ASN
577
34.795
4.587
−16.924
1.00
53.01


ATOM
4144
ND2
ASN
577
36.505
3.863
−18.185
1.00
47.10


ATOM
4145
C
ASN
577
34.830
8.438
−18.898
1.00
29.69


ATOM
4146
O
ASN
577
33.765
8.651
−19.490
1.00
29.69


ATOM
4147
N
LEU
578
35.876
9.243
−18.999
1.00
25.93


ATOM
4148
CA
LEU
578
35.851
10.419
−19.856
1.00
24.60


ATOM
4149
CB
LEU
578
34.984
11.510
−19.216
1.00
24.64


ATOM
4150
CG
LEU
578
34.712
12.813
−19.972
1.00
22.62


ATOM
4151
CD1
LEU
578
33.537
12.583
−20.895
1.00
27.61


ATOM
4152
CD2
LEU
578
34.365
13.949
−19.023
1.00
21.47


ATOM
4153
C
LEU
578
37.278
10.923
−19.968
1.00
24.35


ATOM
4154
O
LEU
578
38.134
10.526
−19.191
1.00
29.74


ATOM
4155
N
ARG
579
37.560
11.745
−20.963
1.00
22.26


ATOM
4156
CA
ARG
579
38.888
12.318
−21.086
1.00
20.20


ATOM
4157
CB
ARG
579
39.371
12.315
−22.528
1.00
22.68


ATOM
4158
CG
ARG
579
39.639
10.946
−23.095
1.00
28.06


ATOM
4159
CD
ARG
579
40.144
11.045
−24.534
1.00
27.95


ATOM
4160
NE
ARG
579
39.100
11.464
−25.456
1.00
26.06


ATOM
4161
C2
ARG
579
39.351
12.036
−26.621
1.00
27.53


ATOM
4162
NH1
ARG
579
40.606
12.248
−26.993
1.00
28.69


ATOM
4163
NH2
ARG
579
38.354
12.417
−27.401
1.00
29.94


ATOM
4164
C
ARG
579
38.750
13.752
−20.664
1.00
18.59


ATOM
4165
O
ARG
579
37.763
14.411
−20.995
1.00
20.40


ATOM
4166
N
LEU
580
39.721
14.235
−19.920
1.00
19.86


ATOM
4167
CA
LEU
580
39.738
15.617
−19.481
1.00
23.93


ATOM
4168
CB
LEU
580
39.916
15.744
−17.970
1.00
28.52


ATOM
4169
CG
LEU
580
38.899
15.198
−16.973
1.00
28.66


ATOM
4170
CD1
LEU
580
39.238
15.819
−15.627
1.00
34.80


ATOM
4171
CD2
LEU
580
37.484
15.569
−17.365
1.00
29.91


ATOM
4172
C
LEU
580
40.984
16.140
−20.148
1.00
25.88


ATOM
4173
O
LEU
580
41.891
15.363
−20.481
1.00
28.77


ATOM
4174
N
PHE
581
41.051
17.445
−20.334
1.00
24.42


ATOM
4175
CA
PHE
581
42.207
18.039
−20.982
1.00
23.21


ATOM
4176
CB
PHE
581
41.802
18.656
−22.324
1.00
23.26


ATOM
4177
CG
PHE
581
40.999
17.757
−23.193
1.00
23.59


ATOM
4178
CD1
PHE
581
39.694
18.090
−23.543
1.00
24.13


ATOM
4179
CD2
PHE
581
41.528
16.541
−23.623
1.00
21.60


ATOM
4180
CET
PHE
581
38.917
17.225
−24.291
1.00
17.92


ATOM
4181
CE2
PHE
581
40.766
15.668
−24.375
1.00
20.87


ATOM
4182
CZ
PHE
581
39.452
16.007
−24.711
1.00
20.99


ATOM
4183
C
PHE
581
42.719
19.128
−20.092
1.00
18.97


ATOM
4184
O
PHE
581
41.943
19.854
−19.505
1.00
21.90


ATOM
4185
N
VAL
582
44.023
19.212
−19.942
1.00
21.20


ATOM
4186
CA
VAL
582
44.601
20.274
−19.151
1.00
24.64


ATOM
4187
CB
VAL
582
45.280
19.739
−17.894
1.00
27.84


ATOM
4188
CG1
VAL
582
45.931
20.889
−17.126
1.00
26.34


ATOM
4189
CG2
VAL
582
44.247
18.998
−17.019
1.00
30.24


ATOM
4190
C
VAL
582
45.579
20.970
−20.079
1.00
25.68


ATOM
4191
O
VAL
582
46.323
20.322
−20.792
1.00
23.96


ATOM
4192
N
GLN
583
45.499
22.291
−20.129
1.00
31.11


ATOM
4193
CA
GLN
583
46.341
23.103
−20.995
1.00
30.37


ATOM
4194
CB
GLN
583
45.485
23.732
−22.078
1.00
37.03


ATOM
4195
CG
GLN
583
44.573
22.758
−22.77
1.00
46.47


ATOM
4196
CD
GLN
583
43.483
23.449
−23.566
1.00
49.92


ATOM
4197
OE1
GLN
583
42.307
23.070
−23.475
1.00
54.21


ATOM
4198
NE2
GLN
583
43.856
24.471
−24.340
1.00
43.85


ATOM
4199
C
GLN
583
46.903
24.236
−20.188
1.00
27.68


ATOM
4200
0
GLN
583
46.271
24.679
−19.247
1.00
27.53


ATOM
4201
N
ANN
584
48.074
24.722
−20.565
1.00
25.21


ATOM
4202
CA
ASN
584
48.667
25.839
−19.862
1.00
25.95


ATOM
4203
CB
ASN
584
49.861
25.395
−19.017
1.00
27.68


ATOM
4204
CO
ASN
584
51.060
25.037
−19.837
1.00
24.49


ATOM
4205
OD1
ASN
584
50.977
24.927
−21.044
1.00
28.26


ATOM
4206
ND2
ASN
584
52.197
24.858
−19.181
1.00
25.26


ATOM
4207
C
ASN
584
49.059
26.829
−20.945
1.00
28.49


ATOM
4208
O
ASN
584
48.928
26.500
−22.129
1.00
29.88


ATOM
4209
N
SER
585
49.496
28.036
−20.579
1.00
27.45


ATOM
4210
CA
SER
585
49.875
29.035
−21.596
1.00
30.77


ATOM
4211
CB
SER
585
49.765
30.456
−21.039
1.00
29.03


ATOM
4212
OG
SER
585
50.325 
30.548
−19.741
1.00
34.88


ATOM
4213
C
SER
585
51.253
28.811
−22.246
1.00
34.38


ATOM
4214
O
SER
585
51.708
29.622
−23.057
1.00
31.24


ATOM
4215 
N
ASN
586
51.899
27.703
−21.867
1.00
37.42


ATOM
4216
CA
ASN
586
53.203
27.294
−22.371
1.00
35.38


ATOM
4217
CB
ASN
586
53.971
26.624 
−21.236
1.00
41.48


ATOM
4218
CG
ASN
586
55.456
26.554
−21.491
1.00
47.03


ATOM
4219
OD1
ASN
586
56.116
25.553
−21.166
1.00
53.23


ATOM
4220
ND2
ASN
586
56.012
27.626
−22.041
1.00
48.92


ATOM
4221
C
ASN
586
52.915
26.292
−23.494
1.00
37.30


ATOM
4222
O
ASN
586
53.795
25.601
−23.990
1.00
40.09


ATOM
4223
N
ASN
587
51.641
26.196
−23.852
1.00
37.02


ATOM
4224
CA
ASN
587
51.159
25.321
−24.903
1.00
36.39


ATOM
4225
CB
ASN
587
51.752
25.738
−26.243
1.00
39.55


ATOM
4226
CG
ASN
567
51.245
27.096
−26.691
1.00
44.89


ATOM
4227
OD1
ASN
587
50.047
27.283
−26.893
1.00
46.33


ATOM
4228
NO2
ASN
587
52.148
28.064
−26.807
1.00
48.96


ATOM
4229
C
ASN
587
51.265
23.826
−24.668
1.00
35.84


ATOM
4230
O
ASN
587
51.377
23.051
−25.616
1.00
37.37


ATOM
4231
N
ASP
588
51.315
23.415
−23.405
1.00
32.62


ATOM
4232
CA
ASP
588
51.367
21.994
−23.085
1.00
27.76


ATOM
4233
CB
ASP
588
51.890
21.743
−21.662
1.00
27.66


ATOM
4234
CG
ASP
588
53.360
22.117
−21.482
1.00
32.14


ATOM
4235
OD1
ASP
588
54.196
21.764
−22.342
1.00
34.35


ATOM
4236
OD2
ASP
588
53.689
22.743
−20.448
1.00
37.89


ATOM
4237
C
ASP
588
49.898
21.604
−23.153
1.00
24.16


ATOM
4238
O
ASP
588
49.042
22.424 
−22.859
1.00
29.81


ATOM
4239
N
PHE
589
49.601
20.378
−23.561
1.00
22.69


ATOM
4240
CA
PHE
589
48.233 
19.911
−23.653
1.00
19.26


ATOM
4241
CB
PHE
589
47.781
19.909 
−25.115
1.00
19.07


ATOM
4242
CG
PHE
589
46.329 
19.561
−25.308
1.00
17.33


ATOM
4243 
CD1 
PHE
589
45.382
20.555 
−25.464 
1.00
13.39


ATOM
4244
CD2 
PHE
589
45.913 
18.242
−25.294 
1.00
14.50


ATOM
4245 
CE1
PHE
589
44.041
20.230 
−25.595 
1.00
14.12


ATOM
4246
CE2
PHE
589
44.581
17.923
−25.426
1.00
16.69


ATOM
4247 
CE
PHE
589
43.645
18.923
−25.576
1.00
13.30


ATOM
4248
C
PHE
589
48.277
18.496
−23.113
1.00
24.44


ATOM
4249
O
PHE
589
48.926
17.640
−23.703
1.00
27.71


ATOM
4250
N
LEU
590
47.610
113.239
−21.991
1.00
26.31


ATOM
4251
CA
LEU
590
47.632
16.907
−21.393
1.00
24.82


ATOM
4252
CB
LEU
590
48.088
16.974
−19.927
1.00
31.03


ATOM
4253
CG
LEU
590
49.371
17.763
−19.647
1.00
34.58


ATOM
4254
CD1
LEU
590
49.688
17.755
−18.166
1.00
39.41


ATOM
4255
CD2
LEU
590
50.529
17.193
−20.440
1.00
40.80


ATOM
4256
C
LEU
590
46.264
16.285
−21.475
1.00
22.29


ATOM
4257
O
LEU
590
45.268
16.965
−21.365
1.00
24.04


ATOM
4258
N
VAL
591
46.220
14.983
−21.670
1.00
21.66


ATOM
4259
CA
VAL
591
44.955
14.302
−21.771
1.00
24.60


ATOM
4260
CB
VAL
591
44.860
13.505
−23.076
1.00
25.35


ATOM
4261
CG1
VAL
591
43.700
12.514
−23.016
1.00
25.77


ATOM
4262
CG2
VAL
591
44.694
14.474
−24.248
1.00
25.42


ATOM
4263
C
VAL
591
44.873
13.383
−20.599
1.00
29.13


ATOM
4264
O
VAL
591
45.784
12.564 
−20.389
1.00
34.66


ATOM
4265
N
ILE
592
43.773
13.510
−19.851
1.00
29.73


ATOM
4266
CA
ILE
592
43.530
12.726
−18.640
1.00
23.90


ATOM
4267
CB
ILE
592
43.552
13.666
−17.407
1.00
21.74


ATOM
4268
CG2
ILE
592
43.189
12.927
−16.148
1.00
16.67


ATOM
4269
CG1
ILE
592
44.940
14.319
−17.319
1.00
19.32


ATOM
4270
CD1
ILE
592
45.293
14.941
−15.995
1.00
24.87


ATOM
4271
C
ILE
592
42.245
11.903
−18.715
1.00
21.42


ATOM
4272
O
ILE
592
41.171
12.448
−18.843
1.00
19.52


ATOM
4273
N
TYR
593
42.380
10.580
−18.684
1.00
22.86


ATOM
4274
CA 
TYR
593
41.242
9.680
−18.751
1.00
26.10


ATOM
4275 
CB
TYR
593
41.630
8.313
−19.346
1.00
34.27


ATOM
4276
CG
TYR
593
42.224
8.392
−20.722
1.00
43.75


ATOM
4277
OD1
TYR
593
43.577
8.706
−20.903
1.00
47.60


ATOM
4278
CE1
TYR
593
44.120
8.903
−22.183
1.00
51.15


ATOM
4279
CD2
TYR
593
41.419
8.257
−21.854
1.00
51.36


ATOM
4280
CE2
TYR
593
41.951
6.450
−23.147
1.00
54.75


ATOM
4281 
CZ
TYR
593
43.300
8.780
−23.301
1.00
56.25


ATOM
4282
OH
TYR
593
43.805
9.043
−24.569
1.00
63.62


ATOM
4283
C
TYR
593
40.806
9.431
−17.344
1.00
27.01


ATOM
4284
O
TYR
593
41.552
8.843
−16.581
1.00
30.49


ATOM
4285
N
ILE
594
39.633
9.918
−16.971
1.00
28.13


ATOM
4286
CA
ILE
594
39.126
9.668
−15.640
1.00
24.97


ATOM
4287
CB
ILE
594
38.397
10.914
−15.060
1.00
26.87


ATOM
4288
CG2
ILE
594
39.366
12.111
−15.052
1.00
24.59


ATOM
4289
CG1
ILE
594
37.127
11.250
−15.855
1.00
25.95


ATOM
4290
CD1
ILE
594
36.068
12.055
−15.092
1.00
20.64


ATOM
4291
C
ILE
594
38.236
8.425
−15.778
1.00
26.39


ATOM
4292
O
ILE
594
37.811
8.087
−16.886
1.00
29.00


ATOM
4293
N
ASN
595
38.083
7.658
−14.703
1.00
28.31


ATOM
4294
CA
ASN
595
37.256
6.446
−14.731
1.00
27.72


ATOM
4295
CB
ASN
595
38.030
5.188
−14.310
1.00
30.83


ATOM
4296
CG
ASN
595
39.106
4.793
−15.305
1.00
32.89


ATOM
4297
OD1
ASN
595
40.238
5.267
−15.224
1.00
36.90


ATOM
4298
ND2
ASN
595
38.770
3.900
−16.225
1.00
33.97


ATOM
4299
C
ASN
595
36.075
6.583
−13.807
1.00
28.15


ATOM
4300
O
ASN
595
36.057
7.435
−12.909
1.00
27.50


ATOM
4301
N
LYS
596
35.107
5.701
−14.021
1.00
27.21


ATOM
4302
CA
LYS
596
33.883
5.672
−13.244
1.00
25.84


ATOM
4303
CD
LYS
596
32.955
4.603
−13.805
1.00
24.28


ATOM
4304
CG
LYS
596
31.686
4.499
−13.047
1.00
24.79


ATOM
4305
CD
LYS
596
30.841
3.335
−13.480
1.00
28.00


ATOM
4306
CE
LYS
596
29.412
3.630
−13.058
1.00
28.21


ATOM
4307
NZ 
LYS
596
28.558
2.421
−13.029
1.00
39.48


ATOM
4308
C
LYS
596
34.231
5.304
−11.819
1.00
26.80


ATOM
4309
O
LYS
596
34.908
4.308
−11.599
1.00
33.76


ATOM
4310
N
THR
597
33.764
6.075
−10.848
1.00
23.21


ATOM
4311
CA
THR
597
34.057
5.755
−9.465
1.00
19.85


ATOM
4312 
CB
THR
597
34.832
6.899
−8.789
1.00
17.47


ATOM
4313
OG1
THR
597
34.170
8.134
−9.045
1.00
23.13


ATOM
4314
CG2
THR
597
36.252
7.008
−9.346
1.00
20.56


ATOM
4315
C
THR
597
32.796
5.445
−8.660
1.00
23.42


ATOM
4316
O
THR
597
32.881
4.846
−7.523
1.00
25.02


ATOM
4317
N
MET
598
31.626
5.762
−9.217
1.00
24.63


ATOM
4318
CA
MET
596
30.350
5.574
−8.508
1.00
29.69


ATOM
4319
CB
MET
598
30.064
6.832
−7.670
1.00
31.74


ATOM
4320
CG
MET
598
30.027
8.092
−8.549
1.00
36.11


ATOM
4321
SD
MET
598
29.755
9.702
−7.775
1.00
37.36


ATOM
4322
CE
MET
598
27.948
9.542
−7.233
1.00
43.52


ATOM
4323
C
MET
598
29.201
5.415
−9.479
1.00
28.31


ATOM
4324
O
MET
598
29.351
5.702
−10.642
1.00
36.08


ATOM
4325
N
ASN
599
28.046
4.978
−9.015
1.00
29.59


ATOM
4326
CA
ASN
599
26.909
4.878
−9.914
1.00
34.34


ATOM
4327
CB
ASN
599
26.040
3.662
−9.612
1.00
36.17


ATOM
4328
CG
ASN
599
26.744
2.360
−9.880
1.00
37.88


ATOM
4329
OD1
ASN
599
27.835
2.326 
−10.422
1.00
44.96


ATOM
4330
ND2
ASN
599
26.124
1.271
−9.484
1.00
46.10


ATOM
4331
C
ASN
599
26.129
6.147
−9.654
1.00
38.09


ATOM
4332
O
ASN
599
26.335
6.794
−8.638
1.00
42.60


ATOM
4333
N
LYS
600
25.187
6.470
10.525
1.00
43.32


ATOM
4334
CA
LYS
600
24.405
7.696
−10.383
1.00
46.30


ATOM
4335
CB
LYS
600
23.445
7.836
−11.562
1.00
52.15


ATOM
4336
CG
LYS
600
24.108
7.719
−12.922
1.00
58.49


ATOM
4337
CD
LYS
600
23.111
7.956
−14.047
1.00
64.43


ATOM
4338
CE
LYS
600
23.755
7.665
−15.395
1.00
69.24


ATOM
4339
NZ
LYS
600
22.804
7.771
−16.540
1.00
75.49


ATOM
4340
C
LYS
600
23.622
7.799
−9.077
1.00
46.95


ATOM
4341
O
LYS
600
23.478
8.882
−8.502
1.00
46.03


ATOM
4342
N
ASP
601
23.092
6.662
−8.642
1.00
49.46


ATOM
4343
CA
ASP
601
22.289
6.577
−7.425
1.00
49.50


ATOM
4344
CB
ASP
601
21.352
5.366
7.507
1.00
50.83


ATOM
4345
CG
ASP
601
22.079
4.065
−7.887
1.00
55.52


ATOM
4346
OD1
ASP
601
21.381
3.044
−8.093
1.00
57.44


ATOM
4347
OD2
ASP
601
23.330
4.050
−7.989
1.00
53.34


ATOM
4348
C
ASP
601
23.130
6.516
−6.152
1.00
50.82


ATOM
4349
O
ASP
601
22.613
6.263
−5.055
1.00
54.21


ATOM
4350
N
ASP
602
24.434
6.710
−6.302
1.00
48.64


ATOM
4351
CA
ASP
602
25.330
6.691
−5.159
1.00
44.01


ATOM
4352
CB
ASP
602
26.717
6.214
−5.575
1.00
40.23


ATOM
4353
CG
ASP
602
26.791
4.738
−5.737
1.00
37.25


ATOM
4354
OD1
ASP
602
27.816
4.259
−6.264
1.00
36.68


ATOM
4355
OD2
ASP
602
25.833
4.054
−5.321
1.00
42.23


ATOM
4356
C
ASP
602
25.467
8.073
−4.558
1.00
44.20


ATOM
4357
O
ASP
602
25.306
9.086
−5.248
1.00
45.97


ATOM
4358
N
ASP
603
25.764
8.107
−3.265
1.00
43.46


ATOM
4359
CA
ASP
603
25.978
9.361
−2.571
1.00
38.92


ATOM
4360
CB
ASP
603
25.448
9.294
−1.135
1.00
48.43


ATOM
4361
CG
ASP
603
23.964
9.623
−1.042
1.00
58.48


ATOM
4362
OD1
ASP
603
23.139
8.684
−1.123
1.00
62.56


ATOM
4363
OD2
ASP
603
23.626
10.824
−0.878
1.00
63.75


ATOM
4364
C
ASP
603
27.477
9.613
−2.573
1.00
31.62


ATOM
4365
O
ASP
603
28.274
8.688
−2.279
1.00
23.41


ATOM
4366
N
LEU
604
27.842
10.881
2.448
1.00
28.74


ATOM
4367
CA
LEU
604
29.226
11.278
−2.422
1.00
27.24


ATOM
4368
CB
LEU
604
29.357
12.764
−2.664
1.00
22.42


ATOM
4369
CG
LEU
604
29.148
13.160
−4.095
1.00
19.01


ATOM
4370
CD1
LEU
604
29.691
14.557
−4.260
1.00
22.34


ATOM
4371
CD2
LEU
604
29.876
12.206
−4.987
1.00
23.64


ATOM
4372
C
LEU
604
29.915
10.933
−1.117
1.00
26.64


ATOM
4373
O
LEU
604
29.977
11.739
−0.206
1.00
30.89


ATOM
4374
N
THR
605
30.398
9.713
−1.020
1.00
27.07


ATOM
4375
CA
THR 
605
31.118
9.302
0.160
1.00
27.67


ATOM
4376
CB
THR
605
30.660
7.934
0.637
1.00
26.78


ATOM
4377
OG1
THR
605
30.956
6.950
−0.361
1.00
35.48


ATOM
4378
CG2
THR
605
29.155
7.972
0.902
1.00
28.06


ATOM
4379
C
THR
605
32.613
9.291
−0.151
1.00
26.21


ATOM
4380
O
THR
605
33.032
9.490
−1.307
1.00
26.25


ATOM
4381
N
TYR
606
33.416
9.058
0.879
1.00
24.88


ATOM
4382
CA
TYR
606
34.852
9.038
0.722
1.00
21.81


ATOM
4383
CB
TYR
606
35.530
8.580
2.010
1.00
19.51


ATOM
4384
CG
TYR
606
37.025
8.692
1.931
1.00
19.63


ATOM
4385
CD1
TYR
606
37.659
9.942
2.019
1.00
19.75


ATOM
4386
CE1
TYR
606
39.032
10.068
1.821
1.00
17.57


ATOM
4387
CD2
TYR
606
37.806
7.566
1.653
1.00
16.29


ATOM
4388
CE2
TYR
606
39.176
7.674
1.457
1.00
16.64


ATOM
4389
CZ
TYR
606
39.782
8.923
1.544
1.00
18.29


ATOM
4390
OH
TYR
606
41.144
9.001
1.411
1.00
23.20


ATOM
4391
C
TYR
606
35.287
8.184
−0.471
1.00
23.40


ATOM
4392
O
TYR
606
35.921
8.691
−1.389
1.00
22.13


ATOM
4393
N
GLN
607
34.870
6.924
−0.509
1.00
27.60


ATOM
4394
CA
GLN
607
35.250
6.036
−1.607
1.00
29.41


ATOM
4395
CB
GLN
607
34.811
4.594
−1.320
1.00
37.18


ATOM
4396
CG
GLN
607
33.310 
4.398
−1.147
1.00
50.31


ATOM
4397
CD
GLN
607
32.949
2.961
−0.777
1.00
59.10


ATOM
4396
OE1
GLN
607
33.005
2.048
−1.610
1.00
66.18


ATOM
4399
NE2
GLN
607
32.595
2.752
0.483
1.00
64.92


ATOM
4400
C
GLN
607
34.832
6.451
−3.027
1.00
29.69


ATOM
4401
O
GLN
607
35.347
5.892
−4.005
1.00
33.55


ATOM
4402
N
THR
608
33.935
7.430
−3.167
1.00
26.45


ATOM
4403
CA
THR
608
33.535
7.861
−4.512
1.00
22.19


ATOM
4404
CB
THR
608
32.188
8.600
−4.519
1.00
18.19


ATOM
4405
CG1
THR
608
32.268
9.728
−3.649
1.00
22.75


ATOM
4406
CG2
THR
608
31.052
7.605
−4.072
1.00
15.16


ATOM
4407
C
THR
608
34.596
8.751
−9.200
1.00
24.93


ATOM
4408
O
THR
608
34.521
8.982
−6.403
1.00
30.46


ATOM
4409
N
PHE
609
35.547 
9.301
−4.450
1.00
20.11


ATOM
4410
CA
PHE
609
36.575
10.116
−5.073
1.00
17.66


ATOM
4411
CB
PHE
609
36.904
11.346
4.251
1.00
16.23


ATOM
4412
CG
PHE
609
35.841
12.399
−4.296
1.00
15.72


ATOM
4413
CD1
PHE
609
34.710
12.290
−3.510
1.00
14.16


ATOM
4414
CD2
PHE
609
35.012
13.537
−5.062
1.00
19.17


ATOM
4415
CE1
PHE
609
33.785
13.285 
−3.467
1.00
13.99


ATOM
4416
CE2
PHE
609
35.080
14.554
−5.031
1.00
17.80


ATOM
4417
CZ
PHE
609
33.965
14.430
−4.225
1.00
19.15


ATOM
4418
C
PHE
609
37.822
9.306
−5.368
1.00
17.82


ATOM
4419
O
PHE
609
38.097
8.300
−4.704
1.00
18.54


ATOM
4420
N
ASP
610
38.589
9.760
−6.354
1.00
16.24


ATOM
4421
CA
ASP
610
39.774
9.043
−6.783
1.00
17.82


ATOM
4422
CB
ASP
610
39.332
7.956
−7.763
1.00
28.02


ATOM
4423
CG
ASP
610
40.381
6.868
−7.980
1.00
30.47


ATOM
4424
OD1
ASP
610
40.134
5.962
−8.812
1.00
36.74


ATOM
4425
OD2
ASP
610
41.442
6.910
−7.330
1.00
35.21


ATOM
4426
C
ASP
610
40.746
10.006
−7.437
1.00
15.64


ATOM
4427
O
ASP
610
40.479
11.198
−7.502
1.00
18.05


ATOM
4428
N
LEU
611
41.888
9.489
−7.888
1.00
19.89


ATOM
4429
CA
LEU
611
42.934
10.287
−8.535
1.00
22.31


ATOM
4430
CB
LEU
611
44.226
10.295
−7.718
1.00
18.56


ATOM
4431
CG
LEU
611
44.209
10.950
−6.347
1.00
20.61


ATOM
4432
CD1
LEU
611
45.472
10.479
−5.583
1.00
22.97


ATOM
4433 
CD2
LEU
611
44.143
12.474
−6.485
1.00
16.32


ATOM
4434
C
LEU
611
43.289 
9.779 
−9.923
1.00
24.26


ATOM
4435
O
LEU
611
43.798 
8.672
−10.070
1.00
28.19


ATOM
4436
N
ALA
612
43.054
10.620
−10.922
1.00
26.19


ATOM
4437
CA
ALA
612
43.367
10.303
−12.297
1.00
25.40


ATOM
4438
CB
ALA
612
42.212
10.711
−13.206
1.00
18.53


ATOM
4439
C
ALA
612
44.604
11.145
−12.583
1.00
26.87


ATOM
4440
O
ALA
612
44.722
12.255
−12.073
1.00
29.03


ATOM
4441
N
THR
613
45.563
10.589
−13.316
1.00
30.85


ATOM
4442
CA
THR
613
46.790
11.306
−13.677
1.00
30.80


ATOM
4443
CB
THR
613
47.954
11.021
−12.682
1.00
31.03


ATOM
4444
OG1
THR
613
49.138
11.733
−13.085
1.00
30.18


ATOM
4445
CG2
THR
613
48.230
9.526
−12.581
1.00
26.60


ATOM
4446
C
THR
613
47.203
10.922
−15.095
1.00
32.15


ATOM
4447
O
THR
613
46.509
10.148
−15.777
1.00
28.30


ATOM
4448 
N
THR
614
48.293
11.511
−15.559
1.00
33.49


ATOM
4449
CA
THR
614
48.793
11.217
−16.885
1.00
37.88


ATOM
4450
CB
THR
614
48.422
12.345
−17.907
1.00
39.76


ATOM
4451 
OG1
THR
614
48.954
12.044 
−19.206
1.00
41.06


ATOM
4452 
CG2 
THR
614
48.905 
13.698
−17.434
1.00
37.77


ATOM
4453
C
THR
614
50.285
11.049
−16.701
1.00
41.10


ATOM
4454
O
THR
614
50.842
11.420
−15.662
1.00
41.53


ATOM
4455
N
ASN
615
50.925
10.411
−17.662
1.00
45.48


ATOM
4456
CA
ASN
615
52.356
10.191
−17.563
1.00
50.76


ATOM
4457
CB
ASN
615
52.724
8.742
−17.888
1.00
56.94


ATOM
4458
CG
ASN
615
51.730
8.072
−18.820
1.00
64.66


ATOM
4459
OD1
ASN
615
50.839
8.714
−19.386
1.00
70.36


ATOM
4460
ND2
ASN
615
51.861
6.759
−18.964 
1.00
69.92


ATOM
4461
C
ASN
615
53.157
11.179 
−18.397
1.00
52.54


ATOM
4462
O
ASN
615
54.353 
10.975
−18.645
1.00
58.56


ATOM
4463
N
SER
616
52.491
12.244
−18.838
1.00
47.84


ATOM
4464
CA
SER
616
53.146
13.299
−19.602
1.00
43.54


ATOM
4465
CH
SER
616
52.307
13.715
−20.805
1.00
43.84


ATOM
4466
OG
SER
616
51.844
12.577
−21.512
1.00
54.32


ATOM
4467 
C
SER
616
53.147
14.417
−18.589
1.00
40.19


ATOM
4468
O
SER
616
52.263
14.471
−17.742
1.00
42.93


ATOM
4469
N
ASN
617
54.150
15.273
−18.617
1.00
37.04


ATOM
4470
CA
ASN
617
54.177
16.358
−17.663
1.00
35.69


ATOM
4471
CB
ASN
617
55.374
16.225
−16.707
1.00
37.96


ATOM
4472
CG
ASN
617
56.672
15.997
−17.423
1.00
39.01


ATOM
4473
OD1
ASN
617
56.979
14.882 
−17.803
1.00
43.35


ATOM
4474
ND2
ASN
617
57.455
17.044
−17.583
1.00
36.32


ATOM
4475
C
ASN
617
54.119
17.732
−18.325
1.00
34.05


ATOM
4476
O
ASN
617
54.092
17.853
−19.554
1.00
30.94


ATOM
4477
N
MET
618
54.030
18.767
−17.500
1.00
33.24


ATOM
4478
CA
MET
618
53.970
20.117
−18.013
1.00
33.10


ATOM
4479
CB
MET
618
52.520
20.636
−18.025
1.00
32.29


ATOM
4480
CG
MET
618
51.949
21.088
−16.702
1.00
29.92


ATOM
4481
SD
MET
618
50.249
21.651
−16.931
1.00
30.97


ATOM
4482
CE
MET
618
50.471
23.199
−16.787 
1.00
32.23


ATOM
4483
C
MET
618
54.921
21.078
−17.297
1.00
31.41


ATOM
4484
O
MET
618
55.356
20.833
−16.165
1.00
31.17


ATOM
4485
N
GLY
619
55.309
22.120
−10.0113
1.00
27.75


ATOM
4486
CA
GLY
619
56.210
23.112
−17.481
1.00
27.31


ATOM
4487
C
GLY
619
55.584
24.468
−17.688
1.00
27.73


ATOM
4488
O
GLY
619
54.616
24.605
−18.457
1.00
23.45


ATOM
4489
N
PHE
620
56.173
25.472
−17.046
1.00
32.05


ATOM
4490
CA
PHE
620
55.670
26.836
−17.087
1.00
34.44


ATOM
4491
CB
PHE
620
55.100
27.179
−15.715
1.00
33.94


ATOM
4492
CO
PHE
620
53.926
26.321
−15.312
1.00
28.19


ATOM
4493
CD1
PHE
620
54.124
25.157
−14.594
1.00
26.00


ATOM
4494
CD2
PHE
620
52.626
26.704
−15.632
1.00
28.04


ATOM
4495
CE1
PHE
620
53.063
24.389
−14.199
1.00
27.86


ATOM
4496
CE2
PHE
620
51.545
25.945
−15.237
1.00
24.13


ATOM
4497
CE
PHE
620
51.762
24.786
−14.518
1.00
29.09


ATOM
4498
C
PHE
620
56.743
27.854
−17.445
1.00
40.11


ATOM
4499 
O
PHE
620
57.936
27.577
−17.300
1.00
43.33


ATOM
4500
N
SER
621
56.317
29.042
−17.877
1.00
46.66


ATOM
4501
CA
SER
621
57.239
30.115
−18.269
1.00
53.27


ATOM
4502
CB
SER
621
57.435
30.146
−19.794
1.00
53.87


ATOM
4503
CG
SER
621
58.551
29.390
−20.252
1.00
59.49


ATOM
4504
C
SER
621
56.763 
31.502 
−17.826
1.00
56.51


ATOM
4505
O
SER
621
55.563 
31.802 
−17.846 
1.00
56.27


ATOM
4506
N
GLY
622
57.720
32.347
−17.453
1.00
58.36


ATOM
4507
CA
GLY
622
57.412
33.705
−17.050
1.00
60.94


ATOM
4508
C
GLY
622
56.503
33.879
−15.858
1.00
62.66


ATOM
4509
O
GLY
622
56.282
32.946
−15.085
1.00
61.90


ATOM
4510
N
ASP
623
55.975
35.092
−15.723
1.00
66.18


ATOM
4511
CA
ASP
623
55.087
35.438
−14.618
1.00
70.95


ATOM
4512
CB
ASP
623
55.539
36.754
−13.940
1.00
73.92


ATOM
4513
CG
ASP
623
55.538
37.966
−14.885
1.00
79.61


ATOM
4514
OD1
ASP
623
55.879
37.814
−16.085
1.00
81.17


ATOM
4515
OD2
ASP
623
55.216 
39.087
−14.405
1.00 
81.72


ATOM
4516
C
ASP
623
53.583
35.457
−14.972
1.00 
71.09


ATOM
4517
O
ASP
623
52.732
35.653 
−14.091
1.00
71.06


ATOM
4518
N
LYS
624
53.260
35.226
−16.247
1.00
69.73


ATOM
4519
CA
LYS
624
51.864
35.193
−16.704
1.00
65.87


ATOM
4520
CB
LYS
624
51.632
36.207
−17.839
1.00
71.81


ATOM
4521
CG
LYS
624
52.482
35.977
−19.090
1.00
81.96


ATOM
4522
CD
LYS
624
52.057
36.892
−20.248
1.00
88.09


ATOM
4523
CE
LYS
624
52.741 
36.515
−21.583
1.00 
91.31


ATOM
4524
NZ
LYS
624
52.259
37.339 
−22.749
1.00 
90.55


ATOM
4525
C
LYS
624
51.448
33.764
−17.119
1.00
59.37


ATOM
4526
O
LYS
624
51.266
33.448
−18.302
1.00 
58.24


ATOM
4527
N
ASN
625
51.314
32.906
−16.115
1.00
49.44


ATOM
4528
CA
ASN
625
50.948
31.519
−16.317
1.00
43.23


ATOM
4529
CB
ASN
625
51.789
30.642
−15.417
1.00
42.10


ATOM
4530
CG
ASN
625
53.236
30.661
−15.816
1.00
40.84


ATOM
4531
OD1
ASN
625
53.650 
29.911
−16.696
1.00
43.01


ATOM
4532
ND2
ASN
625
54.009
31.556
−15.215
1.00
39.55


ATOM
4533
C
ASN
625
49.479
11.251
−16.093
1.00
39.80


ATOM
4534
O
ASN
625
48.923
31.608
−15.064
1.00
39.13


ATOM
4535
N
GLU
626
48.845
30.629
−17.075
1.00
36.93


ATOM
4536
CA
GLU
626
47.423
30.335
−16.993
1.00
38.81


ATOM
4537
CB
GLU
626
46.619
31.272
−17.915
1.00
43.39


ATOM
4538
CG
GLU
626
47.131
32.752
−17.888
1.00
54.84


ATOM
4539
CD
GLU
626
46.114
33.803
−17.389
1.00
56.51


ATOM
4540
OE1
GLU
626
44.916
33.718
−17.760
1.00
55.31


ATOM
4541
OE2 
GLU
626
46.538 
34.745
−16.664
1.00
56.35


ATOM
4542
C
GLU
626
47.183
28.865
−17.313
1.00
34.04


ATOM
4543
O
GLU
626
47.992
28.227
−17.991
1.00 
28.94


ATOM
4544
N
LEU
627
46.117 
28.322 
−16.734
1.00
33.32


ATOM
4545
CA
LEU
627
45.757 
26.925
16.893
1.00
31.13


ATOM
4546
CB
LEU
627
46.061
26.154
−15.584
1.00
28.96


ATOM
4547
CG
LEU
627
46.022 
24.613
−15.610
1.00
27.57


ATOM
4548
CD1
LEU
627
47.403
24.059
−15.709
1.00
22.93


ATOM
4549
CD2
LEU
627
45.351
24.073
−14.391
1.00
28.78


ATOM
4550
C
LEU
627
44.271
26.838
−17.208
1.00
29.90


ATOM
4551
O
LEU
627
43.467
27.467
−16.538
1.00
33.36


ATOM
4552
N
ILE
628
43.912
26.063
−18.241
1.00
30.36


ATOM
4553
CA
ILE
628
42.519
25.902
−18.620
1.00
25.02


ATOM
4554
CB
ILE
628
42.269
26.290
−20.073
1.00
25.94


ATOM
4555
CG2
ILE
628
40.813
26.445
−20.299
1.00
34.05


ATOM
4556
CG1
ILE
628
43.022
27.565
−20.466
1.00
27.41


ATOM
4557
CD1
ILE
628
42.755
28.745
−19.614
1.00
29.63


ATOM
4558
C
ILE
628
42.263
24.411
−16.541
1.00
26.03


ATOM
4559
O
ILE
628
43.131
23.609
−18.886
1.00
28.68


ATOM
4560
N
ILE
629
41.090
24.033
−18.057
1.00
28.18


ATOM
4561
CA
ILE
629
40.700
22.627
−17.960
1.00
25.83


ATOM
4562
CB
ILE
629
40.135
22.262
−16.550
1.00
29.86


ATOM
4563
CG2 
ILE
629
39.803
20.774
−16.463
1.00
32.13


ATOM
4564
CG1
ILE
629
41.152
22.594
−15.466
1.00
36.05


ATOM
4565
CD1
ILE
629
42.503
21.916
−15.642
1.00
41.73


ATOM
4566
C
ILE
629
39.561
22.478 
−18.967
1.00
23.61


ATOM
4567
O
ILE
629
38.693
23.343
−19.063
1.00
19.96


ATOM
4568
N
GLY
630
39.558
21.396
−19.721
1.00
20.85


ATOM
4569
CA
GLY
830
38.500
21.188
−20.682
1.00
23.85


ATOM
4570
C
GLY
630
38.068
19.749
−20.561
1.00
23.37


ATOM
4571
O
GLY
630
38.690
19.001
−19.823
1.00
24.82


ATOM
4572
N
ALA
631
37.033
19.350
−21.286
1.00
20.81


ATOM
4573
CA
ALA
631
36.569
17.982
−21.226
1.00
23.26


ATOM
4574
CB
ALA
631
35.565
17.804
−20.091
1.00
20.73


ATOM
4575
C
ALA
631
35.916
17.661
−22.557
1.00
27.62


ATOM
4576
O
ALA
631
35.650
18.556
−23.356
1.00
29.95


ATOM
4577
N
GLU
632
35.732
16.377
−22.829
1.00
31.92


ATOM
4578
CA
GLU
632
35.078
15.963
−24.059
1.00
32.85


ATOM
4579
CB
GLU
632
35.650
14.644
−24.570
1.00
31.26


ATOM
4580
CG
GLU
632
35.053
13.414
−23.921
1.00
27.95


ATOM
4581
CD
GLU
632
35.713
12.143
−24.385
1.00
36.80


ATOM
4582
OE1
GLU
632
36.369
12.154
−25.451
1.00
40.53


ATOM
4583
OE2
GLU
632
35.590
11.123
−23.679
1.00
41.05


ATOM
4584
C
GLU
632
33.625
15.776
−23.674
1.00
33.61


ATOM
4585
O
GLU
632
33.280
15.718
−22.494
1.00
38.27


ATOM
4586
N
SER
633
32.788
15.582
−24.665
1.00 
32.84


ATOM
4587
CA
SER
633
31.371
15.420
−24.413
1.00
35.35


ATOM
4588
CB
SER
633
30.627
15.688
−25.723
1.00
38.12


ATOM
4589
OG
SER
633
30.955
16.994
−26.189
1.00
46.45


ATOM
4590
C
SER
633
30.937
14.092
−23.809
1.00
34.15


ATOM
4591
O
SER
633
31.566
13.058
−24.025
1.00
35.25


ATOM
4592
N
PHE
634
29.839
14.135
−23.064
1.00
34.80


ATOM
4593
CA
PHE
634
29.262
12.960
−22.419
1.00
37.23


ATOM
4594
CB
PHE
634
29.754
12.854
−20.976 
1.00 
34.83


ATOM
4595
CG
PHE
634
29.346
14.010
−20.117
1.00
30.25


ATOM
4596
CD1
PHE
634
28.262 
13.895
−19.245
1.00
28.96


ATOM
4597
CD2
PHE
634
30.016
15.226
−20.203
1.00
27.74


ATOM
4598
CE1
PHE
634
27.846
14.974
−18.476
1.00
24.91


ATOM
4599
CE2
PHE
634
29.610
16.314
−19.437
1.00
29.50


ATOM
4600
CZ
PHE
634
28.520
16.187
−18.571
1.00
25.99


ATOM
4601
C
PHE
634
27.746
13.173
−22.433
1.00
42.26


ATOM
4602
O
PHE
634
27.280
14.313
−22.607
1.00
43.66


ATOM
4603
N
VAL
635
26.969
12.105
−22.263
1.00
44.81


ATOM
4604
CA
VAL
635
25.510
12.249
−22.268
1.00
49.75


ATOM
4605
CB
VAL
635
24.773
10.914
−22.408
1.00
48.09


ATOM
4606
CG1
VAL
635
24.749
10.479
−23.868
1.00
54.19


ATOM
4607
CG2
VAL
635
25.127
9.860 
21.545
1.00 
48.38


ATOM
4608
C
VAL
635
25.045
12.875
−20.989
1.00
52.73


ATOM
4609
O
VAL
635
25.668
12.694
−19.947
1.00
56.22


ATOM
4610
N
SER
636
23.955
13.622
−21.064
1.00
56.71


ATOM
4611
CA
SER
636
23.401
14.258
−19.676
1.00
60.84


ATOM
4612
CB
SER
636
22.250
15.197
−20.266
1.00
66.55


ATOM
4613
OG
SER
636
21.286
14.545
−21.094
1.00
74.32


ATOM
4614
C
SER
636
22.925
13.169
−18.895
1.00
59.04


ATOM
4615
O
SER
636
22.573
12.049
−19.303
1.00
58.56


ATOM
4616
N
GLY
637
22.934
13.489
−17.605
1.00
55.58


ATOM
4617
CA
GLY
637
22.523
12.511
−16.616 
1.00
52.89


ATOM
4618
C
GLY
637
23.713
11.817
−15.961
1.00
50.21


ATOM
4619
O
GLY
637
23.534
10.968
−15.100
1.00 
54.08


ATOM
4620
N
GLU
638
24.924 
12.120
−16.417
1.00 
45.05


ATOM
4621
CA
GLU
638
26.123
11.544
−15.830
1.00
38.98


ATOM
4622
CB
GLU
638
27.134 
11.150
−16.902
1.00
40.82


ATOM
4623
CG
GLU
638
26.651
10.070
−17.846
1.00
41.29


ATOM
4624
CD 
GLU
638
26.536
8.713
−17.198 
1.00 
44.15


ATOM
4625
OE1
GLU
639
26.859
8.570
−16.008
1.00
51.56


ATOM
4626
OE2
GLU
638
26.140
7.758
−17.087 
1.00 
48.24


ATOM
4627
C
GLU
638
26.694
12.632
−14.936
1.00
37.82


ATOM
4628
O
GLU
638
26.748
13.809
−15.318
1.00
40.61


ATOM
4629
N
LYS
639
27.078
12.246
−13.730
1.00
31.64


ATOM
4630 
CA
LYS
639
27.601
13.190
12.765
1.00
25.56


ATOM
4631
CB
LYS
639
27.080 
12.853
−11.366
1.00
29.28


ATOM
4632
CG
LYS
639
25.593
12.600
−11.246
1.00
34.14


ATOM
4633
CD
LYS
639
25.316
11.994
−9.857
1.00
48.20


ATOM
4634
CE
LYS
639
23.830
11.816
9.571
1.00
50.33


ATOM
4635
NZ
LYS
639
23.172
10.838
−10.481
1.00
57.45


ATOM
4636
C
LYS
639
29.110
13.139
−12.133
1.00
20.16


ATOM
4637
O
LYS
639
29.686
12.056
−12.594
1.00
21.41


ATOM
4638
N
ILE
640
29.134
14.308
−12.856
1.00
16.72


ATOM
4639
CA
ILE
640
31.177
14.457
−12.802
1.00
13.62


ATOM
4640
CB
ILE
640
31.825
14.866
−14.158
1.00
13.79


ATOM
4641
CG2
ILE
640
33.295
15.154
−13.943
1.00
15.50


ATOM
4642
CG1
ILE
640
31.751
13.734
−15.191
1.00
13.55


ATOM
4643
CD1
ILE
640
30.610
13.831
−16.190
1.00
11.62


ATOM
4644
C
ILE
640
31.418
15.572
−11.809
1.00
18.26


ATOM
4645
O
ILE
640
30.845
16.646
−11.936
1.00
20.94


ATOM
4646
N
TYR
641
32.210
15.288
−10.778
1.00
20.12


ATOM
4647
CA
TYR
641
32.548
16.254
−9.741
1.00
17.06


ATOM
4648
CB
TYR
641
32.093
15.736
−8.394
1.00
12.33


ATOM
4649
CG
TYR
641
30.629
15.427
−8.353
1.00
19.71


ATOM
4650
CD1
TYR
641
30.170
14.134
−8.582
1.00
20.72


ATOM
4651
CE1
TYR
641
28.821
13.833
−8.508
1.00
25.35


ATOM
4652
CD2
TYR
641
29.697
16.421
−8.050
1.00
18.05


ATOM
4653
CE2
TYR
641
28.358
16.132
−7.968
1.00
26.09


ATOM
4654
CZ
TYR
641
27.924
14.834
−8.191
1.00
24.94


ATOM
4655
OH
TYR
641
26.597
14.530
−8.023
1.00
32.32


ATOM
4656
C
TYR
641
34.060
16.389
−9.708
1.00
18.01


ATOM
4657
O
TYR
641
34.779
15.391
−9.614
1.00
18.42


ATOM
4658
N
ILE
642
34.550
17.606
−9.833
1.00
16.45


ATOM
4659
CA
ILE
642
35.988
17.608
−9.791
1.00
20.87


ATOM
4660 
CB
ILE
642
36.491
16.575
−11.029
1.00
20.47


ATOM
4561
CG2
ILE
642
37.958
18.793
−10.911
1.00
20.81


ATOM
4662 
CG1
ILE
642
36.235
17.760
−12.306
1.00
19.36


ATOM
4663
CD1
ILE
642
36.571
18.515
−13.566
1.00
21.85


ATOM
4664
C
ILE
642
36.246 
18.593
−8.512
1.00
20.68


ATOM
4665
O
ILE
642
35.470
19.494
8.187
1.00
22.38


ATOM
4666
N
ASP
643
37.304
18.230
−7.783
1.00
20.18


ATOM
4667
CA
ASP
643
37.655
18.879
−6.548
1.00
16.65


ATOM
4668 
CB
ASP
643
37.531
17.821
−5.382
1.00
22.35


ATOM
4669
CG
ASP
643
38.028
18.294
−4.024
1.00
26.15


ATOM
4670
OD1
ASP
643
37.750
19.453
−3.625
1.00
25.20


ATOM
4671 
OD2
ASP
643
38.684
17.464
−3.338
1.00
24.15


ATOM
4672
C
ASP
643
39.030
19.587
−6.511
1.00
20.45


ATOM
4573
O
ASP
643
39.096
20.821
−6.361
1.00
24.99


ATOM
4674
N
LYS
644
40.116
18.842
−6.724
1.00
16.96


ATOM
4675
CA
LYS
644
41.457
19.428
−6.714
1.00
17.58


ATOM
4676
CB
LYS
644
42.246
18.997
−5.470
1.00
19.80


ATOM
4677
CG
LYS
644
41.602
19.216
−4.117
1.00
22.38


ATOM
4678
CD
LYS
644
41.412
20.666
3.773
1.00
23.96


ATOM
4679
CE
LYS
644
41.051
20.791
−2.310
1.00
20.00


ATOM
4680
NZ
LYS
644
40.046
19.745
−1.948
1.00
20.46


ATOM
4681
C
LYS
644
42.332
19.024
−7.884
1.00
18.74


ATOM
4682
O
LYS
644
42.322
17.872
−8.296
1.00
21.48


ATOM
4683
N
ILE
645
43.168
19.954
−8.329
1.00
17.54


ATOM
4684
CA
ILE
645
44.132
19.717
−9.388
1.00
17.59


ATOM
4685
CB
ILE
645
44.241
20.931
−10.352
1.00
21.58


ATOM
4686
CG2
ILE
645
45.150
20.602
−11.541
1.00
23.33


ATOM
4687
CG1
ILE
645
42.860
21.330
−10.878
1.00
25.80


ATOM
4688
CD1
ILE
645
42.170
20.258
−11.698
1.00
23.99


ATOM
4689
C
ILE
645
45.416
19.643
−8.565
1.00
16.72


ATOM
4690
O
ILE
645
45.684
20.540
−7.782
1.00
19.90


ATOM
4691
N
GLU
646
46.185
18.568
−8.686
1.00
18.31


ATOM
4692
CA
GLU
646
47.429
18.450
−7.922
1.00
16.72


ATOM
4693
CB
GLU
646
47.459 
17.158
−7.100
1.00
13.74


ATOM
4694
CG
GLU
646
46.218
16.841
−6.292
1.00
11.87


ATOM
4695
CD
GLU
646
46.475
15.711
−5.331
1.00
21.72


ATOM
4696
OE1
GLU
646
47.074
14.707
−5.762
1.00
22.74


ATOM
4697
OE2
GLU
646
46.104
15.822
−4.145
1.00
25.76


ATOM
4698
C
GLU
646
48.679
18.501
−8.804
1.00
15.32


ATOM
4699
O
GLU
646
48.728
17.894
−9.855
1.00
17.66


ATOM
4700
N
PHE
647
49.701
19.198
−8.337
1.00
18.90


ATOM
4701
CA
PHE
647
50.950
19.316
−9.060 
1.00
20.74


ATOM
4702
CB
PHE
647
51.299 
20.783
−9.253
1.00
22.54


ATOM
4703
CG 
PHE
647
50.309
21.508
−10.096
1.00
16.80


ATOM
4704
CD1
PHE
647
49.263
22.185
−9.513
1.00
15.88


ATOM
4705
CD2
PHE
647
50.388
21.442
−11.474
1.00
15.98


ATOM
4706
CE1
PHE
647
48.297
22.779
−10.285
1.00
19.07


ATOM
4707
CE2
PHE
647
49.440
22.026
−12.251
1.00
17.20


ATOM
4708
CZ
PHE
647
48.385
22.699
−11.658
1.00
21.92


ATOM
4709
C
PHE
647
52.048
18.597
−8.327
1.00
23.01


ATOM
4710
O
PHE
647
52.285
18.827
−7.145
1.00
25.26


ATOM
4711
N
ILE
648
52.682
17.676
−9.032
1.00
27.24


ATOM
4712
CA
ILE
648
53.766
16.884
−8.481
1.00
28.26


ATOM
4713
CB
ILE
648
53.499
15.385
−8.728
1.00
28.25


ATOM
4714
CG2
ILE
648
54.433
14.542
7.874
1.00
30.94


ATOM
4715
CG1
ILE
648
52.033
15.045
−8.428
1.00
26.62


ATOM
4716
CD1
ILE
648
51.634
13.616
−8.796
1.00
24.38


ATOM
4717
C
ILE
648
55.009
17.299
−9.260
1.00
29.24


ATOM
4718
O
ILE
648
54.979
17.314
−10.488
1.00
29.14


ATOM
4719
N
PRO
649
56.079 
17.735
−8.566
1.00
29.81


ATOM
4720
CD
PRO
649
56.096
18.156
−7.167
1.00
26.84


ATOM
4721
CA
PRO
649
57.323
18.153
−9.232
1.00
33.95


ATOM
4722
CB
PRO
649
58.101
18.818
−8.111
1.00
25.42


ATOM
4723
CG
PRO
649
57.039
19.324
−7.242
1.00
10.57


ATOM
4724
C
PRO
649
58.075
16.947
−9.760
1.00
39.61


ATOM
4725
O
PRO
649
58.648
16.186
−8.980
1.00
44.73


ATOM
4726
N
VAL
650
58.046
16.755
−11.075
1.00
44.21


ATOM
4727
CA
VAL
650
58.714
15.616
−11.696
1.00
48.14


ATOM
4728
CB
VAL
650
58.401
15.403
−13.180
1.00
45.37


ATOM
4729
CG1
VAL
650
59.150
14.313
−13.731
1.00
47.12


ATOM
4730
CG2
VAL
650
56.923
15.311
−13.407
1.00
44.38


ATOM
4731
C
VAL
650
60.196
15.817
−11.595
1.00
54.89


ATOM
4732
O
VAL
650
60.766
16.662
−12.294
1.00
56.42


ATOM
4733
N
GLN
651
60.817
15.043
−10.718
1.00
62.10


ATOM
4734
CA
GLN
651
62.253
15.136
−10.510
1.00
71.53


ATOM
4735
CB
GLN
651
62.568
15.175
−9.013
1.00
74.84


ATOM
4736
CG
GLN
651
61.980
16.384
−8.294
1.00
80.23


ATOM
4737
CD
GLN
651
62.380
16.453
6.828
1.00
86.44


ATOM
4738
OE1
GLN
651
61.827
17.251
−6.065
1.00
88.07


ATOM
4739
NE2
GLN
651
63.341
15.616
−6.420 
1.00
88.91


ATOM
4740
C
GLN
651
62.978
13.981
−11.185
1.00
75.09


ATOM
4741
O
GLN
651
63.591
13.140
−10.517
1.00
76.97


ATOM
4742
N
LEU
652
62.892
13.966
−12.513
1.00
78.20


ATOM
4743
CA
LEU
652
63.505
12.943
−13.354
1.00
80.82


ATOM
4744
CB
LEU
652
63.468
13.404
−14.811
1.00
83.43


ATOM
4745
CG
LEU
652
62.069
13.518
−15.418
1.00
84.78


ATOM
4746
CD1
LEU
652
62.119
14.172
−16.798
1.00
86.36


ATOM
4747
CD2
LEU
652
61.447
12.120
−15.483
1.00 
85.69


ATOM
4748
C
LEU
652
64.942
12.620
−12.960
1.00
82.59


ATOM
4749
OT1
LEU
652
65.216
11.449
−12.608
1.00
84.20


ATOM
4750
OT2
LEU
652
65.772
13.555
−13.013
1.00
86.03


ATOM
4751
O
HOH
1
39.600
24.576
11.813
1.00
12.17


ATOM
4752
O
HOH
2
40.792
27.069
11.597
1.00
25.65


ATOM
4753
O
HOH
3
43.758
26.829
11.570
1.00
13.86


ATOM
4754
O
HOH
4
55.446
23.281
8.689
1.00
39.72


ATOM
4755
O
HOH
5
54.367
13.815
2.943
1.00
30.80


ATOM
4756
O
HOH
6
57.911
14.284
16.519
1.00
30.98


ATOM
4757
O
HOH
7
38.642
1.242
15.206
1.00
35.24


ATOM
4758
O
HOH
8
39.462
−1.232
13.462
1.00 
39.99


ATOM
4759
O
HOH
9
30.581
9.208
17.185
1.00
12.58


ATOM
4760
O
HOH
10
43.871
15.044
17.131
1.00
13.07


ATOM
4761
O
HOH
11
57.356
−3.646
2.453
1.00
47.02


ATOM
4762
O
HOH
12
45.059
−5.877
8.478
1.00
34.13


ATOM
4763
O
HOH
13
42.458
6.455
1.498
1.00
37.54


ATOM
4764
O
HOH
14
38.876
8.797
−1.848
1.00
29.14


ATOM
4765
O
HOH
15
29.008
5.736
8.141
1.00
33.53


ATOM
4766
O
HOH
16
26.319
10.581
4.482
0.50
34.39


ATOM
4767
O
HOH
17
28.858
9.435
5.261
1.00
27.54


ATOM
4768
O
HOH
18
30.989
23.542
6.740
1.00
27.62


ATOM
4769
O
HOH
19
29.511
20.588
9.501
1.00
33.81


ATOM
4770
O
HOH
20
45.641
8.025
6.242
1.00
20.04


ATOM
4771
O
HOH
21
97.722
6.464
1.525
1.00
54.78


ATOM
4772
O
HOH
22
48.699
27.494
1.748
1.00
30.06


ATOM
4773
O
HOH
23
22.565
23.551
4.174
1.00
50.71


ATOM
4774
O
HOH
24
31.780
26.111
1.799
1.00
36.59


ATOM
4775
O
HOH
25
35.833
19.538
5.174
1.00
22.44


ATOM
4776
O
HOH
26
31.698
41.144
14.808
1.00
26.75


ATOM
4777
O
HOH
27
22.848
21.286
−7.106
0.50
44.55


ATOM
4778
O
HOH
28
28.149
35.263
−5.749
0.50
27.52


ATOM
4779
O
HOH
29
38.768
38.465
1.897
1.00
23.59


ATOM
4780
O
HOH
30
36.036
48.871 
−3.323
1.00
37.96


ATOM
4781
O
HOH
31
15.228
54.291
25.146
1.00
38.59


ATOM
4782
O
HOH
32
30.188
40.575
−3.853
1.00
25.30


ATOM
4783
O
HOH
33
41.541
42.499
−1.499
1.00
33.25


ATOM
4784 
O
HOH
34
38.585
45.910
14.986
1.00
46.67


ATOM
4785
O
HOH
35
39.850
41.334
2.080
1.00 
44.36


ATOM
4786
O
HOH
36
42.846
31.690
−10.923
1.00
21.98


ATOM
4787
O
HOH
37
43.450
12.688
−1.919
1.00
24.87


ATOM
4788
O
HOH
38
39.038
13.837
2.118
1.00
27.10


ATOM
4789
O
HOH
39
37.928
5.313
−6.284
1.00
50.72


ATOM
4790
O
HOH
40
24.875
4.116 
−12.560
0.50
29.43


ATOM
4791
O
HOH
41
55.553
35.810
−18.611
0.50
42.33


ATOM
4792
O
HOH
42
46.764
34.401
3.319
1.00
52.37


ATOM
4793
O
HOH
43
38.723
6.598
−19.519
1.00
45.34


ATOM
4794
O
HOH
44
65.474
2.330
6.882
0.50
53.47


ATOM
4795
O
HOH
45
62.312
4.587
26.852
0.50
32.00


ATOM
4796
O
HOH
46
71.750
−5.969
18.706
1.00 
37.47


ATOM
4797
O
HOH
47
58.775
1.057
6.153
1.00
30.94


ATOM
4798
O
HOH
48
45.175
6.998
1.494
1.00
34.82


ATOM
4799
O
HOH
49
63.008
22.148
−6.426
0.50
29.98


ATOM
4800
O
HOH
50
41.462
18.172
−0.139
1.00
30.33


ATOM
4801
O
HOH
51
32.560
21.738
2.331 
1.00 
29.61


ATOM
4802
O
HOH
52
14.519
37.667
0.321
0.50
37.60


ATOM
4803
O
HOH
53
42.144
26.546
23.602
1.00
41.27


ATOM
4804
O
HOH
54
54.172 
23.431
6.327
1.00 
37.79


ATOM
4805
O
HOH
55
58.450
21.703
4.673
1.00
52.24


ATOM
4806
O
HOH
56
53.956
13.326
12.026
1.00
49.78


ATOM
4807
O
HOH
57
44.302
20.733
35.040
0.50
36.95


ATOM
4808
O
HOH
58
25.387
22.349 
29.216
1.00
51.45


ATOM
4809
O
HOH
59
34.276
5.690
35.854
1.00
57.79


ATOM
4810
O
HOH
60
32.55
1 5.395
26.460
1.00
44.81


ATOM
4811
O
HOH
61
68.914
9.067
22.100
1.00
30.57


ATOM
4812
O
HOH
62
69.607
4.662
7.019
1.00
68.86


ATOM
4813
O
HOH
63
49.122
−5.437 
19.972
0.50
32.90


ATOM
4814
O
HOH
64
35.071
2.983
13.525
1.00
57.51


ATOM
4815
O
HOH
65
69.205
−0.072
8.173
0.50
30.67


ATOM
4816
O
HOH
66
59.499
−8.455
0.875
1.00
42.81


ATOM
4817
O
HOH
67
43.513
−7.338
4.202
1.00
58.46


ATOM
4818
O
HOH
68
24.836
23.892
5.544
1.00
25.95


ATOM
4819
O
HOH
69
12.711
29.928
21.875
1.00
59.62


ATOM
4820
O
HOH
70
11.349
34.141
13.154
1.00
37.81


ATOM
4821
O
HOH
71
24.776
30.568
19.682
1.00
32.79


ATOM
4822
O
HOH
72
35.674
22.015
5.914
1.00
25.68


ATOM
4823
O
HOH
73
39.992
22.649
0.839
1.00
26.71


ATOM
4824
O
HOH
74
33.304
19.359
1.262
1.00
21.88


ATOM
4825
O
HOH
75
34.676
25.968
−1.544
1.00
25.47


ATOM
4826
O
HOH
76
38.335
29.492
3.495
1.00
26.33


ATOM
4827
O
HOH
77
34.285
32.668
−0.876
1.00
32.85


ATOM
4828
O
HOH
78
26.762
34.664
2.474
1.00
38.71


ATOM
4829
O
HOH
79
26.382
37.981
−5.606
1.00
42.31


ATOM
4830
O
HOH
80
14.711
46.855
−4.418
0.50
35.57


ATOM
4831
O
HOH
81
48.032
50.318
1.569
1.00
49.00


ATOM
4832
O
HOH
82
40.081
36.290
12.462
1.00
18.52


ATOM
4833
O
HOH
83
48.045
27.052
−4.303
1.00
33.60


ATOM
4834
O
HOH
84
55.768
32.124
−2.269
0.50
25.70


ATOM
4999
O
HOH
249
59.791
24.221
−18.460
1.00
49.24


ATOM
5000
O
HOH
250
28.695
10.159
−21.579
1.00
57.39


ATOM
5001
O
HOH
251
23.322
9.183
−18.681
0.50
36.90


END




























9.2 CRYSTAL COORDINATES OF CRY3A




















HEADER
TOXIN
22-JUN-94
1DLC
1DLC
2










COMPND
DELTA-ENDOTOXIN CRYIIIA (BT13)
1DLC
3


SOURCE
(BACILLUS THURINGIENSIS. SUBSPECIES TENEBRIONIS)
1DLC
4


AUTHOR
J. LI
1DLC
5












REVDAT
1
30-SEP-94 1DLC
0
1DLC
6


REMARK
1


1DLC
7











REMARK
1
REFERENCE 1
1DLC
8












REMARK
1
AUTH
J. LI. J CARROLL,D. J. ELLAR
1DLC
9


REMARK
1
TITL
CRYSTAL STRUCTURE OF INSECTICIDAL DELTA-ENDOTOXIN
1DLC
10


REMARK
1
TITL 2
FROM BACILLUS THURINGIENSIS AT 2.5 ANGSTROMS
1DLC
11


REMARK
1
TITL 3
RESOLUTION
1DLC
12















REMARK
1
REF
NATURE
V. 353
815
1991
1DLC
13














REMARK
1
REFN
ASTM NATUAS
UK ISSN 0028-0836
0006
1DLC
14











REMARK
1
REFERENCE 2
1DLC
15












REMARK
1
AUTH
J. LI, R HENDERSON,J. CARROLL, D. ELLAR
1DLC
16


REMARK
1
TITL
X-RAY ANALYSIS OF THE CRYSTALLINE PARASPORAL
1DLC
17


REMARK
1
TITL 2
INCLUSION IN BACILLUS THURINGIENSIS VAR.
1DLC
18


REMARK
1
TITL 3
TENEBRIONIS
1DLC
19















REMARK
1
REF
J.MOL.BIOL.
V. 199
543
1988
1DLC
20














REMARK
1
REFN
ASTM JMOBAK
UK ISSN 0022-2836
0070
1DLC
21










REMARK
2
1DLC
22











REMARK
2
RESOLUTION. 2.5 ANGSTROMS.
1DLC
23










REMARK
3
1DLC
24











REMARK
3
REFINEMENT.
1DLC
25












REMARK
3
PROGRAM
X-PLOR
1DLC
26


REMARK
3
AUTHORS
BRUNGER
1DLC
27


REMARK
3
R VALUE
 0.183
1DLC
28













REMARK
3
RMSD BOND DISTANCES
 0.011
ANGSTROMS
1DLC
29


REMARK
3
RMSD BOND ANGLES
 1.58
DEGREES
1DLC
30


REMARK
3
RMSD DIHEDRAL ANGLES
25.06
DEGREES
1DLC
31


REMARK
3
RMSD IMPROPER ROTATION
 1.471
DEGREES
1DLC
32


REMARK
3



1DLC
33


REMARK
3
NUMBER OF REFLECTIONS
27726

1DLC
34













REMARK
3
RESOLUTION RANGE
16.0-2.5
ANGSTROMS
1DLC
35













REMARK
3
DATA CUTOFF
 0.0
SIGMA (F)
1DLC
36


REMARK
3
PERCENT COMPLETION
 100.

1DLC
37











REMARK
3

1DLC
38












REMARK
3
NUMBER OF PROTEIN ATOMS
4697
1DLC
39


REMARK
3
NUMBER OF SOLVENT ATOMS
106
1DLC
40










REMARK
3
1DLC
41











REMARK
3
THE ATOMIC MODEL INCLUDED RESIDUES 61-44 OF THE PROTEIN
1DLC
42


REMARK
3
AND 106 BOUND WATER MOLECULES. BULK SOLVENT CONTRIBUTION
1DLC
43


REMARK
3
TO THE STRUCTURE FACTOR WAS CALCULATED USING THE CCP4
1DLC
44


REMARK
3
PROGRAM SFALL AND INCLUDED IN THIS REFINEMENT.
1DLC
45


REMARK
3

1DLC
46


REMARK
4

1DLC
47


REMARK
4
CRYIIIA BELONGS TO THE “CRY” FAMILY OF DELTA-ENDOTOXINS,
1DLC
48


REMARK
4
WHICH ARE PORE-FORMING INSECTICIDAL PROTEIN TOXINS
1DLC
49


REMARK
4
CONTAINED IN THE CRYSTALLINE PARASPORAL INCLUSIONS OF
1DLC
50


REMARK
4
BACILLUS THURINGIENSIS. THE SUBCLASS III IS TOXIC
1DLC
51


REMARK
4
SPECIFICALLY TO COLEOPTERAN INSECTS. I.E., BEETLES. THEY
1DLC
52


REMARK
4
FUNCTION BY BINDING TO MIDGUT EPITHELIAL CELLS AND INDUCE
1DLC
53


REMARK
4
COLLOIDOSMOTIC LYSIS.
1DLC
54


REMARK
5

1DLC
55


REMARK
5
THE SEQUENCE OF CRYIIIA IN THE ATOMIC MODEL IS TAKEN FROM:
1DLC
56


REMARK
5
HOEFTE, H., SEURINCK, J., VAN HOUTVEN. A. AND VAECK.
1DLC
57


REMARK
5
(1987) NUCLEIC ACIDS RES. 15:7183. EMBL ACCESSION NUMBER
1DLC
58


REMARK
5
P07130. ENTRY NAME CR70 BACTT. RESIDUES 1-57 ARE
1DLC
59


REMARK
5
REMOVED IN THE MATURE TOXIN. RESIDUES 58-60 ARE
1DLC
60


REMARK
5
INVISIBLE IN THE CRYSTAL STRUCTURE.
1DLC
61


REMARK
6

1DLC
62


REMARK
6
THE STRUCTURE WAS REPORTED IN PAPER [1] ABOVE AFTER
1DLC
63


REMARK
6
PRELIMINARY REFINEMENT. THE COORDINATES BEING DEPOSITED
1DLC
64


REMARK
6
HERE RESULTED FROM FURTHER REFINEMENT.
1DLC
65


REMARK
7

1DLC
66


REMARK
7
CROSS REFERENCE TO SEQUENCE DATABASE
1DLC
67












REMARK
7
SWISS-PROT ENTRY NAME
PDR ENTRY CHAIN NAME
1DLC
68











REMARK
7
CR70_BACTT
1DLC
69
























SEQRES
1
584
THR
THR
LYS
ASP
VAL
ILE
GLN
LYS
GLY
ILE
SER
VAL
VAL
1DLC
70


SEQRES
2
584
GLY
ASP
LEU
LEU
GLY
VAL
VAL
GLY
PHE
PRO
PHE
GLY
GLY
1DLC
71


SEQRES
3
584
ALA
LEU
VAL
SER
PHE
TYR
THR
ASN
PHE
LEU
ASN
THR
ILE
1DLC
72


SEQRES
4
584
TRP
PRO
SER
GLU
ASP
PRO
TRP
LYS
ALA
PHE
MET
GLU
GLN
1DLC
73


SEQRES
5
584
VAL
GLU
ALA
LEU
MET
ASP
GLN
LYS
ILE
ALA
ASP
TYR
ALA
1DLC
74


SEQRES
6
584
LYS
ASN
LYS
ALA
LEU
ALA
GLU
LED
GLN
GLY
LEU
GLN
ASN
1DLC
75


SEQRES
7
584
ASN
VAL
GLU
ASP
TYR
VAL
SER
ALA
LEU
SER
SER
TRP
GLN
1DLC
76


SEQRES
8
584
LYS
ASN
PRO
VAL
SER
SER
ARG
ASN
PRO
HIS
SER
GLN
GLY
1DLC
77


SEQRES
9
584
ARG
ILE
ARG
GLU
LEU
PHE
SER
GLN
ALA
GLU
SER
HIS
PHE
1DLC
78


SEQRES
10
584
ARG
ASN
SER
MET
PRO
SER
PHE
ALA
ILE
SER
GLY
TYR
GLU
1DLC
79


SEQRES
11
584
VAL
LEU
PHE
LEU
THR
THR
TYR
ALA
GLN
ALA
ALA
ASN
THR
1DLC
80


SEQRES
12
584
HIS
LEU
PHE
LEU
LEU
LYS
ASP
ALA
GLN
ILE
TYR
GLY
GLU
1DLC
81


SEQRES
13
584
GLU
TRP
GLY
TYR
GLU
LYS
GLU
ASP
ILE
ALA
GLU
PHE
TYR
1DLC
82


SEQRES
14
584
LYS
ARG
GLN
LEU
LYS
LEU
THR
GLN
GLU
TYR
THR
ASP
HIS
1DLC
83


SEQRES
15
584
CYS
VAL
LYS
TRP
TYR
ASN
VAL
GLY
LEU
ASP
LYS
LEU
ARG
1DLC
84


SEQRES
16
584
GLY
SER
SER
TYR
GLU
SER
TRP
VAL
ASN
PHE
ASN
ARG
TYR
1DLC
85


SEQRES
17
584
ARG
ARG
GLU
MET
THR
LEU
THR
VAL
LEU
ASP
LEU
ILE
ALA
1DLC
86


SEQRES
18
584
LEU
PHE
PRO
LEU
TYR
ASP
VAL
ARG
LED
TYR
PRO
LYS
GLU
1DLC
87


SEQRES
19
584
VAL
LYS
THR
GLU
LEU
THR
ARG
ASP
VAL
LEU
THR
ASP
PRO
1DLC
88


SEQRES
20
584
ILE
VAL
GLY
VAL
ASN
ASN
LEU
ARG
SLY
TYR
GLY
THR
THR
1DLC
S9


SEQRES
21
584
PHE
SER
ASN
ILE
GLU
ASN
TYR
ILE
ARG
LYS
PRO
HIS
LEU
1DLC
90


SEQRES
22
584
PHE
ASP
TYR
LEU
HIS
ARG
ILE
GLN
PHE
HIS
THR
ARG
PHE
1DLC
91


SEQRES
23
584
GLN
PRO
GLY
TYR
TYR
GLY
ASN
ASP
SER
PHE
ASN
TYR
TRP
1DLC
92


SEQRES
24
584
SER
GLY
ASN
TYR
VAL
SER
THR
ARG
PRO
SER
ILE
GLY
SER
1DLC
93


SEQRES
25
584
ASN
ASP
ILE
ILE
THE
SER
PRO
PHE
TYR
GLY
ASN
LYS
SER
1DLC
94


SEQRES
26
584
SER
GLU
PRO
VAL
GLN
ASN
LEU
GLU
PHE
ASN
GLY
GLU
LYS
1DLC
95


SEQRES
27
584
VAL
TYR
ARG
ALA
VAL
ALA
ASN
THR
ASN
LEU
ALA
VAL
TRP
1DLC
96


SEQRES
28
584
PRO
SER
ALA
VAL
TYR
SER
GLY
VAL
THE
LYS
VAL
GLU
PHE
1DLC
97


SEQRES
29
584
SER
GLN
TYR
ASN
ASP
THR
GLN
ASP
GLU
ALA
SER
THR
GLN
1DLC
98


SEQRES
30
584
THR
TYR
ASP
SER
LYS
ARG
ASN
VAL
GLY
ALA
VAL
SER
TRP
1DLC
99


SEQRES
31
584
ASP
SER
ILE
ASP
GLN
LEU
PRO
PRO
GLU
THR
THR
ASP
GLU
1DLC
100


SEQRES
32
584
PRO
LED
GLU
LYS
GLY
TYR
SER
HIS
GLN
LEU
ASN
TYR
VAL
1DLC
101


SEQRES
33
584
MET
CYS
PHE
LEU
MET
GLN
GLY
SER
ARG
GLY
THR
ILE
PRO
1DLC
102


SEQRES
34
584
VAL
LEU
THR
TRP
THR
HIS
LYS
SER
VAL
ASP
PHE
PHE
ASN
1DLC
103


SEQRES
35
584
MET
ILE
ASP
SER
LYS
LYS
ILE
THR
GLN
LEU
PRO
LEU
VAL
1DLC
104


SEQRES
36
584
LYS
ALA
TYR
LYS
LEU
GLN
SER
GLY
ALA
SER
VAL
VAL
ALA
1DLC
105


SEQRES
37
584
GLY
PRO
ARG
PHE
THR
GLY
GLY
ASP
ILE
ILE
GLN
CYS
THR
1DLC
106


SEQRES
38
584
GLU
ASN
GLY
SER
ALA
ALA
THR
ILE
TYR
VAL
THR
PRO
ASP
1DLC
107


SEQRES
39
584
VAL
SER
TYR
SER
GLN
LYS
TYR
ARG
ALA
ARG
ILE
HIS
TYR
1DLC
108


SEQRES
40
584
ALA
SER
THR
SER
GLN
ILE
THR
PHE
THR
LEU
SER
LEU
ASP
1DLC
109


SEQRES
41
584
GLY
ALA
PRO
PHE
ASN
GLN
TYR
TYR
PHE
ASP
LYS
THR
ILE
1DLC
110


SEQRES
42
584
ASN
LYS
GLY
ASP
THR
LEU
THR
TYR
ASN
SER
PHE
ASN
LEU
1DLC
111


SEQRES
43
584
ALA
SER
PHE
SER
THR
PRO
PRE
GLU
LEU
SER
GLY
ASN
ASN
1DLC
112


SEQRES
44
584
LEU
GLN
ILE
GLY
VAL
THR
GLY
LEU
SER
ALA
GLY
ASP
LYS
1DLC
113


SEQRES
45
584
VAL
TYR
ILE
ASP
LYS
ILE
GLU
PHE
ILE
PRO
VAL
ASN

1DLC
114










FTNOTE
1
1DLC
115











FTNOTE'
1
RESIDUE ARG 443 IS MODELED IN TWO CONFORMATIONS.
1DLC
116












FORMUL
2
HOH
*106(H2 O1)
1DLC
117

















CRYST1
117.090
134.260
104.500
90.00
90.00
90.00
C 2 2 21
8
1DLC
118













ORIGX1
1.000000
0.000000
0.000000
0.00000
1DLC
119


ORIGX2
0.000000
1.000000
0.000000
0.00000
1DLC
120


ORIGX3
0.000000
0.000000
1.000000
0.00000
1DLC
121


SCALE1
0.008540
0.000000
0.000000
0.00000
1DLC
122


SCALE2
0.000000
0.007448
0.000000
0.00000
1DLC
123


SCALE3
0.000000
0.000000
0.009569
0.00000
1DLC
124



















ATOM
1
N
THR
61
29.687
34.216
28.976
1.00
81.05

1DLC
125


ATOM
2
CA
THR
61
29.891
35.382
28.051
1.00
79.92

1DLC
126


ATOM
3
C
THR
61
30.511
36.562
28.809
1.00
78.01

1DLC
127


ATOM
4
O
THR
61
30.542
35.553
30.039
1.00
78.99

1DLC
128


ATOM
5
CR
THR
61
28.566
35.808
27.359
1.00
81.30

1DLC
129


ATOM
6
CG1
THR
61
28.815
36.906
26.470
1.00
81.70

1DLC
130


ATOM
7
CG2
THR
61
27.514
36.206
28.388
1.00
82.00

1DLC
131


ATOM
8
N
THR
62
31.035
37.542
28.074
1.00
74.62

1DLC
132


ATOM
9
CA
THR
62
31.689
38.735
28.648
1.00
71.74

1DLC
133


ATOM
10
C
THR
62
32.886
38.447
29.565
1.00
68.69

1DLC
134


ATOM
11
O
THR
62
33.402
39.348
30.227
1.00
67.78

1DLC
135


ATOM
12
CB
THR
62
30.702
39.676
29.416
1.00
72.26

1DLC
136


ATOM
13
OG1
THR
62
30.353
39.108
30.689
1.00
70.81

1DLC
137


ATOM
14
CG2
THR
62
29.446
39.935
28.595
1.00
72.45

1DLC
138


ATOM
15
N
LYS
63
33.367
37.206
29.542
1.00
65.97

1DLC
139


ATOM
16
CA
LYS
63
34.505
36.792
30.369
1.00
64.35

1DLC
140


ATOM
17
C
LYS
63
35.716
37.704
30.142
1.00
60.39

1DLC
141


ATOM
18
O
LYS
63
36.514
37.928
31.050
1.00
58.79

1DLC
142


ATOM
19
CB
LYS
63
34.903
35.327
30.097
1.00
67.19

1DLC
143


ATOM
20
CG
LYS
63
33.799
34.413
29.553
1.00
71.54

1DLC
144


ATOM
21
CD
LYS
63
33.671
34.566
28.032
1.00
77.47

1DLC
145


ATOM
22
CE
LYS
63
32.583
33.671
27.434
1.00
79.28

1DLC
146


ATOM
23
NZ
LYS
63
32.253
34.062
26.018
1.00
79.70

1DLC
147


ATOM
24
N
ASP
64
35.829
38.242
28.928
1.00
56.53

1DLC
148


ATOM
25
CA
ASP
64
36.919
39.146
28.568
1.00
52.15

1DLC
149


ATOM
26
C
ASP
64
37.009
40.333
29.526
1.00
46.41

1DLC
150


ATOM
27
O
ASP
64
38.033
40.514
30.176
1.00
45.73

1DLC
151


ATOM
28
CH
ASP
64
36.747
39.647
27.131
1.00
59.48

1DLC
152


ATOM
29
CG
ASP
64
37.811
40.666
26.729
1.00
66.90

1DLC
153


ATOM
30
OD1
ASP
64
39.020
40.354
26.064
1.00
70.25

1DLC
154


ATOM
31
OD2
ASP
64
37.436
41.780
26.280
1.00
70.28

1DLC
155


ATOM
32
N
VAL
55
35.937
41.120
29.631
1.00
40.49

1DLC
156


ATOM
33
CA
VAL
65
35.929
42.276
30.535
1.00
36.43

1DLC
157


ATOM
34
C
VAL
65
35.981
41.865
31.998
1.00
33.19

1DLC
158


ATOM
35
O
VAL
65
36.481
42.612
32.843
1.00
33.95

1DLC
159


ATOM
36
CB
VAL
65
34.721
43.233
30.319
1.00
34.54

1DLC
160


ATOM
37
CG1
VAL
65
31.823
43.903
28.969
1.00
35.83

1DLC
161


ATOM
38
CG2
VAL
65
33.405
42.501
30.473
1.00
36.36

1DLC
162


ATOM
39
N
ILE
66
35.474
10.676
32.299
1.00
28.34

1DLC
163


ATOM
40
CA
ILE
66
35.506
40.187
33.666
1.00
26.84

1DLC
164


ATOM
41
C
ILE
66
36.953
39.854
34.029
1.00
27.43

1DLC
165


ATOM
42
O
ILE
66
37.405
40.153
35.138
1.00
27.70

1DLC
166


ATOM
43
CB
ILE
66
34.576
38.962
33.857
1.00
26.34

1DLC
167


ATOM
44
CG
ILE
66
33.138
39.362
33.533
1.00
26.70

1DLC
168


ATOM
45
CG2
ILE
66
34.627
38.459
35.299
1.00
23.41

1DLC
169


ATOM
46
CD1
ILE
66
32.625
40.529
34.377
1.00
27.75

1DLC
170


ATOM
47
N
GLN
67
37.696
39.313
33.063
1.00
26.53

1DLC
171


ATOM
48
CA
GLN
67
39.100
38.962
33.278
1.00
27.75

1DLC
172


ATOM
49
C
GLN
67
39.931
40.231
33.442
1.00
25.84

1DLC
173


ATOM
50
O
GLN
67
40.772
40.315
34.340
1.00
23.91

1DLC
174


ATOM
51
CB
GLN
67
39.639
38.122
32.122
1.00
32.89

1DLC
175


ATOM
52
CC 
GLN
67
40.360
36.852
32.576
1.00
39.52

1DLC
176


ATOM
53
CD
GLN
67
41.866
37.006
32.729
1.00
44.36

1DLC
177


ATOM
54
OE1
GLN
67
42.613
36.080
32.442
1.00
52.02

1DLC
178


ATOM
55
NE2
GLN
67
42.316
38.156
33.188
1.00
45.86

1DLC
179


ATOM
56
N
LYS
68
39.688
41.216
32.580
1.00
22.97

1DLC
180


ATOM
57
CA
LYS
68
40.388
42.496
32.664
1.00
24.69

1DLC
181


ATOM
58
C
LYS
68
40.100
43.123
34.030
1.00
24.93

1DLC
182


ATOM
59
O
LYS
68
41.010
43.577
34.725
1.00
28.51

1DLC
183


ATOM
60
CB
LYS
68
39.926
43.436
31.550
1.00
26.18

1DLC
184


ATOM
61
CG
LYS
68
40.265
42.946
30.158
1.00
29.43

1DLC
185


ATOM
62
CD
LYS
68
39.812
43.936
29.098
1.00
35.76

1DLC
186


ATOM
63
CE
LYS
68
40.187
43.453
27.710
1.00
37.35

1DLC
187


ATOM
64
NZ
LYS
68
41.635
43.087
27.651
1.00
43.99

1DLC
188


ATOM
65
N
GLY
69
38.832
43.092
34.431
1.00
21.56

1DLC
189


ATOM
66
CA
GLY
69
38.443
43.632
35.717
1.00
22.62

1DLC
190


ATOM
67
C
GLY
69
39.161
42.937
36.859
1.00
22.36

1DLC
191


ATOM
68
O
GLY
69
39.750
43.599
37.709
1.00
25.64

1DLC
192


ATOM
69
N
ILE
70
39.144
41.606
36.862
1.00
20.46

1DLC
193


ATOM
70
CA
ILE
70
39.801
40.821
37.908
1.00
19.46

1DLC
194


ATOM
71
C
ILE
70
41.318
41.037
37.943
1.00
21.56

1DLC
195


ATOM
72
O
ILE
70
41.911
41.211
39.015
1.00
20.57

1DLC
196


ATOM
73
CB
ILE
70
39.452
39.303
37.773
1.00
21.33

1DLC
197


ATOM
74
CG1
ILE
70
37.584
39.074
38.191
1.00
21.90

1DLC
198


ATOM
75
CG2
ILE
70
40.413
38.437
38.609
1.00
17.07

1DLC
199


ATOM
76
CD1
ILE
70
37.517
37.621
38.227
1.00
15.87

1DLC
200


ATOM
77
N
SER
71
41.929
41.072
36.763
1.00
22.90

1DLC
201


ATOM
78
CA
SER
71
43.371
41.277
36.627
1.00
24.32

1DLC
202


ATOM
79
C
SER
71
43.861
42.626
37.141
1.00
23.60

1DLC
203


ATOM
80
O
SER
71
44.873
42.697
37.815
1.00
23.30

1DLC
204


ATOM
81
CB
SER
71
43.795
41.111
35.171
1.00
25.61

1DLC
205


ATOM
82
OG
SER
71
43.497
39.802
34.733
1.00
34.05

1DLC
206


ATOM
83
N
VAL
72
43.153
43.698
36.787
1.00
20.94

1DLC
207


ATOM
84
CA
VAL
72
43.532
45.037
37.232
1.00
20.83

1DLC
208


ATOM
85
C
VAL
72
43.556
45.113
38.755
1.00
21.24

1DLC
209


ATOM
86
O
VAL
72
44.528
45.584
39.346
1.00
23.21

1DLC
210


ATOM
87
CB
VAL
72
42.572
46.104
36.673
1.00
22.69

1DLC
211


ATOM
88
CG1
VAL
72
42.850
47.458
37.309
1.00
24.49

1DLC
212


ATOM
89
CG2
VAL
72
42.738
46.203
35.165
1.00
25.89

1DLC
213


ATOM
90
N
VAL
73
42.493
44.613
39.380
1.00
19.28

1DLC
214


ATOM
91
CA
VAL
73
42.377
44.600
40.834
1.00
15.95

1DLC
215


ATOM
92
C
VAL
73
43.523
43.777
41.406
1.00
15.90

1DLC
216


ATOM
93
O
VAL
73
44.169
44.181
42.373
1.00
19.54

1DLC
217


ATOM
94
CB
VAL
73
40.993
44.023
41.277
1.00
15.19

1DLC
218


ATOM
95
CG1
VAL
73
40.977
43.726
42.762
1.00
11.40

1DLC
219


ATOM
96
CG2
VAL
73
39.882
45.005
40.936
1.00
8.14

1DLC
226


ATOM
97
N
GLY
74
43.804
42.043
40.773
1.00
18.80

1DLC
221


ATOM
98
CA
GLY
74
44.888
41.786
41.225
1.00
20.25

1DLC
222


ATOM
99
C
GLY
74
46.250
42.465
41.136
1.00
22.94

1DLC
223


ATOM
100
O
GLY
74
47.061
42.353
42.051
1.00
24.08

1DLC
224


ATOM
101
N
ASP
75
46.493
43.183
40.043
1.00
21.18

1DLC
225


ATOM
102
CA
ASP
75
47.750
43.892
39.849
1.00
25.01

1DLC
226


ATOM
103
C
ASP
75
47.858
45.070
40.810
1.00
25.78

1DLC
227


ATOM
104
O
ASP
75
48.904
45.296
41.423
1.00
27.64

1DLC
228


ATOM
105
CB
ASP
75
47.873
44.394
38.404
1.00
31.86

1DLC
229


ATOM
106
CG
ASP
75
48.091
43.263
37.397
1.00
35.66

1DLC
230


ATOM
107
OD1
ASP
75
48.511
42.153
37.802
1.00
39.68

1DLC
231


ATOM
108
OD2
ASP
75
47.847
43.487
36.189
1.00
42.21

1DLC
232


ATOM
109
N
LEU
76
46.772
45.819
40.947
1.00
26.59

1DLC
233


ATOM
110
CA
LEU
70
46.755
46.967
41.847
1.00
24.97

1DLC
234


ATOM
111
C
LEU
76
47.065
46.549
43.276
1.00
23.34

1DLC
235


ATOM
112
O
LEU
76
47.690
47.303
44.018
1.00
23.84

1DLC
236


ATOM
113
CB
LEU
76
45.410
47.678
41.790
1.00
24.54

1DLC
237


ATOM
114
CG
LEU
76
45.214
48.589
40.588
1.00
21.89

1DLC
238


ATOM
115
CD1
LEU
76
43.743
48.951
40.475
1.00
23.58

1DLC
239


ATOM
116
CD2
LEU
76
46.081
49.830
40.737
1.00
20.30

1DLC
240


ATOM
117
N
LEU
77
46.655
45.339
43.649
1.00
22.54

1DLC
241


ATOM
118
CA
LEU
77
46.928
44.834
44.992
1.00
23.75

1DLC
242


ATOM
119
C
LEU
77
48.440
44.786
45.278
1.00
24.55

1DLC
243


ATOM
120
O
LEU
77
48.864
44.713
46.435
1.00
25.25

1DLC
244


ATOM
121
CB
LEU
77
46.290
43.453
45.198
1.00
22.14

1DLC
245


ATOM
122
CG
LEU
77
44.817
43.440
45.633
1.00
23.83

1DLC
240


ATOM
123
CD1
LEU
77
44.298
42.016
45.692
1.00
21.52

1DLC
247


ATOM
124
CD2
LEU
77
44.652
44.116
46.991
1.00
19.85

1DLC
248


ATOM
125
N
GLY
78
49.240
44.837
44.215
1.00
24.11

1DLC
249


ATOM
126
CA
GLY
78
50.684
44.823
44.356
1.00
23.63

1DLC
250


ATOM
127
C
GLY
78
51.337
46.203
44.380
1.00
25.07

1DLC
251


ATOM
128
O
GLY
78
52.481
46.329
44.795
1.00
28.69

1DLC
252


ATOM
129
N
VAL
79
50.634
47.238
43.930
1.00
24.83

1DLC
253


ATOM
130
CA
VAL
79
51.190
48.599
43.920
1.00
22.91

1DLC
254


ATOM
131
C
VAL
79
50.332
49.576
44.728
1.00
23.48

1DLC
255


ATOM
132
O
VAL
79
50.285
50.775
44.461
1.00
28.13

1DLC
256


ATOM
133
CB
VAL
79
51.361
49.136
42.474
1.00
19.52

1DLC
257


ATOM
134
CG1
VAL
79
52.454
48.379
41.769
1.00
19.64

1DLC
258


ATOM
135
CG2
VAL
79
50.072
49.007
41.701
1.00
18.98

1DLC
259


ATOM
136
N
VAL
80
49.666
49.047
45.736
1.00
23.04

1DLC
260


ATOM
137
CA
VAL
80
48.795
49.835
46.588
1.00
21.33

1DLC
261


ATOM
138
C
VAL
80
49.632
50.446
47.753
1.00
24.09

1DLC
262


ATOM
139
O
VAL
80
50.565
49.810
48.267
1.00
24.41

1DLC
263


ATOM
140
CB
VAL
80
47.575
48.936
46.982
1.00
16.03

1DLC
264


ATOM
141
CG1
VAL
80
47.581
48.546
48.431
1.00
16.04

1DLC
265


ATOM
142
CG2
VAL
80
46.295
49.576
46.531
1.00
8.70

1DLC
266


ATOM
143
N
GLY
81
49.345
51.694
48.123
1.00
23.56

1DLC
267


ATOM
144
CA
GLY
81
50.134
52.364
49.150
1.00
20.79

1DLC
268


ATOM
145
C
GLY
81
51.281
53.055
48.416
1.00
24.82

1DLC
269


ATOM
146
O
GLY
81
51.128
53.400
47.244
1.00
26.66

1DLC
270


ATOM
147
N
PRE
82
52.419
53.292
49.067
1.00
26.10

1DLC
271


ATOM
148
CA
PHE
82
53.567
53.934
48.401
1.00
24.09

1DLC
272


ATOM
149
C
PHE
82
54.383
52.816
47.747
1.00
24.46

1DLC
273


ATOM
150
O
PRE
82
55.143
52.114
48.425
1.00
26.54

1DLC
274


ATOM
151
CE
PHE
82
54.429
54.684
49.417
1.00
22.55

1DLC
275


ATOM
152
CG
PHE
82
55.329
55.721
48.808
1.00
27.94

1DLC
276


ATOM
153
CD1
PHE
82
56.374
55.359
47.963
1.00
31.41

1DLC
277


ATOM
154
CD2
PHE
82
55.136
57.069
49.080
1.00
30.52

1DLC
278


ATOM
155
CE1
PHE
82
57.215
56.327
47.395
1.00
31.44

1DLC
279


ATOM
156
CE2
PHE
82
55.972
58.048
48.518
1.00
31.81

1DLC
280


ATOM
157
CZ
PHE
82
57.012
57.673
47.674
1.00
30.74

1DLC
281


ATOM
158
N
PRO
83
54.278
52.671
46.412
1.00
23.78

1DLC
282


ATOM
159
CA
PRO
83
54.988
51.632
45.663
1.00
26.68

1DLC
283


ATOM
160
C
PRO
83
56.418
51.983
45.255
1.00
30.99

1DLC
284


ATOM
161
O
PRO
83
56.763
53.156
45.095
1.00
31.60

1DLC
285


ATOM
162
CS
PRO
83
54.107
51.475
44.430
1.00
23.32

1DLC
286


ATOM
163
CG
PRO
83
53.801
52.905
44.103
1.00
24.30

1DLC
287


ATOM
164
CD
PRO
83
53.578
53.578
45.481
1.00
24.78

1DLC
288


ATOM
165
N
PHE
84
57.248
50.962
45.054
1.00
35.72

1DLC
289


ATOM
166
CA
PHE
84
58.610
51.222
44.622
1.00
37.68

1DLC
290


ATOM
167
C
PHE
84
58.622
51.455
43.101
1.00
36.16

1DLC
291


ATOM
168
O
PHE
94
57.928
50.768
42.344
1.00
35.44

1DLC
292


ATOM
169
CB
PHE
84
59.585
50.142
45.149
1.00
43.35

1DLC
293


ATOM
170
CG
PHE
84
60.018
49.109
44.139
1.00
53.50

1DLC
294


ATOM
171
CD1
PHE
84
60.836
49.450
43.055
1.00
55.35

1DLC
295


ATOM
172
CD2
PHE
84
59.682
47.768
44.324
1.00
58.10

1DLC
296


ATOM
173
CE1
PHE
84
61.311
48.473
42.178
1.00
57.42

1DLC
297


ATOM
174
CE2
PHE
84
60.156
46.778
43.448
1.00
59.43

1DLC
298


ATOM
175
CZ
PHE
84
60.971
47.133
42.375
1.00
58.66

1DLC
299


ATOM
176
N
GLY
85
59.320
52.515
42.701
1.00
34.26

1DLC
300


ATOM
177
CA
GLY
85
59.427
52.923
41.308
1.00
31.90

1DLC
301


ATOM
178
C
GLY
85
59.414
51.874
40.213
1.00
31.82

1DLC
302


ATOM
179
O
GLY
85
58.751
52.062
39.193
1.00
33.93

1DLC
303


ATOM
180
N
GLY
86
60.183
50.803
40.385
1.00
30.52

1DLC
304


ATOM
181
CA
GLY
86
60.205
49.750
39.380
1.00
30.25

1DLC
305


ATOM
182
C
GLY
86
58.868
49.035
39.291
1.00
29.35

1DLC
306


ATOM
183
O
GLY
86
58.369
48.752
38.204
1.00
29.94

1DLC
307


ATOM
184
N
ALA
87
58.273
48.764
40.445
1.00
27.51

1DLC
308


ATOM
185
CA
ALA
87
56.980
48.103
40.492
1.00
26.98

1DLC
309


ATOM
186
C
ALA
87
55.905
48.972
39.833
1.00
27.22

1DLC
310


ATOM
187
O
ALA
87
55.085
48.473
39.064
1.00
31.29

1DLC
311


ATOM
188
CB
ALA
87
56.606
47.796
41.927
1.00
28.74

1DLC
312


ATOM
189
N
LEU
88
55.944
50.276
40.106
1.00
26.83

1DLC
313


ATOM
190
CA
LEU
88
54.982
51.239
39.551
1.00
25.69

1DLC
314


ATOM
191
C
LEU
88
55.005
51.264
38.018
1.00
27.21

1DLC
315


ATOM
192
O
LEU
88
53.955
51.221
37.364
1.00
27.87

1DLC
316


ATOM
193
CB
LEU
88
55.274
52.637
40.110
1.00
27.08

1DLC
317


ATOM
194
CG
LEU
88
54.208
53.744
40.185
1.00
27.37

1DLC
318


ATOM
195
CD1
LEU
88
54.504
54.862
39.217
1.00
24.51

1DLC
319


ATOM
196
CD2
LEU
88
52.817
53.179
39.972
1.00
30.41

1DLC
320


ATOM
197
N
VAL
89
56.207
51.308
37.448
1.00
28.98

1DLC
321


ATOM
198
CA
VAL
89
56.369
51.325
35.993
1.00
28.90

1DLC
322


ATOM
199
C
VAL
89
55.898
50.001
35.387
1.00
29.01

1DLC
323


ATOM
200
O
VAL
89
55.165
49.999
34.396
1.00
28.22

1DLC
324


ATOM
201
CB
VAL
89
57.828
51.644
35.594
1.00
27.87

1DLC
325


ATOM
202
CG1
VAL
89
57.975
51.678
34.082
1.00
24.97

1DLC
326


ATOM
203
CG2
VAL
89
58.222
52.996
36.169
1.00
28.04

1DLC
327


ATOM
204
N
SER
90
56.278
48.885
36.013
1.00
30.42

1DLC
328


ATOM
205
CA
SER
90
55.856
47.551
35.559
1.00
32.29

1DLC
329


ATOM
206
C
SER
90
54.342
47.506
35.485
1.00
32.55

1DLC
330


ATOM
207
O
SER
90
53.765
47.085
34.479
1.00
34.09

1DLC
331


ATOM
208
CB
SER
90
56.295
46.472
36.544
1.00
34.34

1DLC
332


ATOM
209
OG
SER
90
57.694
46.292
36.525
1.00
46.73

1DLC
333


ATOM
210
N
PHE
91
53.701
47.924
36.575
1.00
31.31

1DLC
334


ATOM
211
CA
PHE
91
52.249
47.956
36.633
1.00
29.77

1DLC
335


ATOM
212
C
PHE
91
51.712
48.737
35.441
1.00
29.48

1DLC
336


ATOM
213
O
PHE
91
50.912
48.224
34.668
1.00
31.29

1DLC
337


ATOM
214
CB
PHE
91
51.758
48.622
37.924
1.00
29.25

1DLC
338


ATOM
215
CG
PHE
91
50.285
48.926
37.911
1.00
27.24

1DLC
339


ATOM
216
CD1
PHE
91
49.354
47.923
38.151
1.00
24.90

1DLC
340


ATOM
217
CD2
PHE
91
49.828
50.197
37.584
1.00
24.88

1DLC
341


ATOM
218
CE1
PHE
91
47.996
48.176
38.057
1.00
24.42

1DLC
342


ATOM
219
CE2
PHE
91
48.469
50.458
37.489
1.00
23.79

1DLC
343


ATOM
220
CZ
PRE
91
47.554
49.446
37.724
1.00
22.85

1DLC
344


ATOM
221
N
TYR
92
52.176
49.972
35.294
1.00
29.52

1DLC
345


ATOM
222
CA
TYR
92
51.736
50.835
34.211
1.00
29.00

1DLC
346


ATOM
223
C
TYR
92
51.764
50.214
32.815
1.00
30.26

1DLC
347


ATOM
224
O
TYR
92
50.858
50.466
32.017
1.00
30.35

1DLC
348


ATOM
225
CR
TYR
92
52.524
52.141
34.222
1.00
29.47

1DLC
349


ATOM
226
CG
TYR
92
51.925
53.227
35.088
1.00
27.60

1DLC
350


ATOM
227
CD1
TYR
92
50.587
53.603
34.947
1.00
27.51

1DLC
351


ATOM
228
CD2
TYR
92
52.716
53.938
35.993
1.00
24.64

1DLC
352


ATOM
229
CE1
TYR
92
50.062
54.669
35.677
1.00
25.83

1DLC
353


ATOM
230
CE2
TYR
92
52.197
54.999
36.726
1.00
21.65

1DLC
354


ATOM
231
CZ
TYR
92
50.876
55.363
36.562
1.00
23.23

1DLC
355


ATOM
232
OH
TYR
92
50.380
56.440
37.260
1.00
21.02

1DLC
356


ATOM
233
N
THR
93
52.774
49.396
32.515
1.00
30.64

1DLC
357


ATOM
234
CA
THR
93
52.839
48.771
31.190
1.00
32.20

1DLC
358


ATOM
235
C
THR
93
51.743
47.724
31.004
1.00
33.10

1DLC
359


ATOM
236
O
THR
93
51.126
47.658
29.945
1.00
34.96

1DLC
360


ATOM
237
CB
THR
93
54.226
48.171
30.866
1.00
33.29

1DLC
361


ATOM
238
OG1
THR
93
54.487
47.041
31.704
1.00
39.40

1DLC
362


ATOM
239
CG2
THR
93
55.308
49.213
31.080
1.00
34.17

1DLC
363


ATOM
240
N
ASN
94
51.479
46.926
32.038
1.00
33.41

1DLC
364


ATOM
241
CA
ASN
94
50.406
45.929
31.965
1.00
36.98

1DLC
365


ATOM
242
C
ARM
94
49.089
46.685
31.856
1.00
35.78

1DLC
366


ATOM
243
O
ASN
94
48.244
46.375
31.018
1.00
37.99

1DLC
367


ATOM
244
CB
ASN
94
50.348
45.068
33.230
1.00
44.19

1DLC
368


ATOM
245
CG
ASN
94
51.398
43.978
33.253
1.00
51.52

1DLC
369


ATOM
246
OD1
ASN
94
52.109
43.753
32.272
1.00
54.17

1DLC
370


ATOM
247
ND2
ASN
94
51.490
43.277
34.381
1.00
54.88

1DLC
371


ATOM
248
N
PHE
95
48.942
47.692
32.713
1.00
33.93

1DLC
372


ATOM
249
CA
PHE
95
47.755
48.538
32.771
1.00
33.38

1DLC
373


ATOM
250
C
PHE
95
47.398
49.047
31.385
1.00
32.29

1DLC
374


ATOM
251
O
PHE
95
46.270
48.895
30.927
1.00
34.55

1DLC
375


ATOM
252
CB
PHE
95
48.017
49.715
33.713
1.00
33.16

1DLC
376


ATOM
253
CO
PHE
95
46.806
50.551
34.005
1.00
32.63

1DLC
377


ATOM
254
CD1
PHE
95
45.602
49.953
34.386
1.00
30.05

1DLC
378


ATOM
255
CD2
PHE
95
46.873
51.941
33.920
1.00
31.23

1DLC
379


ATOM
256
CE1
PHE
95
44.485
50.726
34.678
1.00
29.10

1DLC
380


ATOM
257
CE2
PHE
95
45.761
52.726
34.210
1.00
28.92

1DLC
381


ATOM
258
CZ
PHE
95
44.566
52.117
34.590
1.00
31.14

1DLC
382


ATOM
259
N
LED
96
48.380
49.614
30.702
1.00
34.97

1DLC
383


ATOM
260
CA
LEO
96
48.166
50.126
29.360
1.00
35.92

1DLC
384


ATOM
261
C
LEO
96
47.771
49.028
28.384
1.00
36.69

1DLC
385


ATOM
262
O
LEO
96
46.903
49.230
27.539
1.00
39.72

1DLC
306


ATOM
263
CB
LEO
96
49.409
50.869
28.862
1.00
39.72

1DLC
387


ATOM
264
CG
LEO
96
49.427
52.393
29.075
1.00
42.79

1DLC
388


ATOM
265
CD1
LEO
96
49.134
52.771
30.537
1.00
43.39

1DLC
389


ATOM
266
CD2
LEO
96
50.776
52.937
28.633
1.00
45.04

1DLC
390


ATOM
267
N
ASN
97
48.371
47.853
28.523
1.00
37.06

1DLC
391


ATOM
268
CA
ASN
97
48.050
46.738
27.630
1.00
40.47

1DLC
392


ATOM
269
C
ASN
97
46.665
46.150
27.893
1.00
39.49

1DLC
393


ATOM
270
O
ASN
97
45.986
45.680
26.981
1.00
41.34

1DLC
394


ATOM
271
CB
ASN
97
49.103
45.629
27.741
1.00
40.91

1DLC
395


ATOM
272
CG
ASN
97
50.459
46.054
27.219
1.00
42.87

1DLC
396


ATOM
273
OD1
ASN
97
51.489
45.589
27.699
1.00
47.11

1DLC
397


ATOM
274
ND2
ASN
97
50.469
46.941
26.234
1.00
38.77

1DLC
398


ATOM
275
N
THR
98
46.244
46.214
29.144
1.00
38.36

1DLC
399


ATOM
276
CA
THR
98
44.959
45.677
29.543
1.00
36.23

1DLC
400


ATOM
277
C
THR
98
43.798
46.638
29.306
1.00
33.62

1DLC
401


ATOM
278
O
THR
98
42.957
46.412
28.445
1.00
34.42

1DLC
402


ATOM
279
CB
THR
98
44.983
45.290
31.039
1.00
37.03

1DLC
403


ATOM
280
OG1
THR
98
46.134
44.479
31.302
1.00
36.69

1DLC
404


ATOM
281
CG2
THR
98
43.726
44.516
31.427
1.00
39.60

1DLC
405


ATOM
282
N
ILE
99
43.796
47.740
10.045
1.00
31.37

1DLC
406


ATOM
283
CA
ILE
99
42.720
48.722
29.983
1.00
28.14

1DLC
407


ATOM
204
C
ILE
99
42.837
49.822
28.923
1.00
30.20

1DLC
408


ATOM
285
O
ILE
99
41.827
50.244
28.351
1.00
30.60

1DLC
409


ATOM
286
CB
I LE
99
42.523
49.378
31.383
1.00
25.44

1DLC
410


ATOM
287
CG1
ILE
99
42.274
48.301
32.445
1.00
23.31

1DLC
411


ATOM
288
CG2
ILE
99
41.389
50.388
31.362
1.00
24.47

1DLC
412


ATOM
289
CD1
ILE
99
41.002
47.504
32.253
1.00
24.55

1DLC
413


ATOM
290
N
TRP
100
44.056
50.270
28.631
1.00
29.78

1DLC
414


ATOM
291
CA
TRP
100
44.226
51.355
27.661
1.00
30.90

1DLC
415


ATOM
292
C
TRP
100
44.913
51.060
26.312
1.00
34.13

1DLC
416


ATOM
293
O
TRP
100
45.593
51.932
25.755
1.00
37.64

1DLC
417


ATOM
294
CB
TRP
100
44.916
52.548
28.341
1.00
25.25

1DLC
418


ATOM
295
CG
TRP
100
44.160
53.138
29.509
1.00
21.47

1DLC
419


ATOM
296
CD1
TRP
100
44.326
52.835
30.836
1.00
19.22

1DLC
420


ATOM
297
CD2
TRP
100
43.173
54.181
29.459
1.00
19.56

1DLC
421


ATOM
298
NE1
TRP
100
43.517
53.635
31.611
1.00
19.74

1DLC
422


ATOM
299
CE2
TRP
100
42.799
54.469
30.795
1.00
19.03

1DLC
423


ATOM
300
CE3
TRP
100
42.576
54.905
28.418
1.00
16.14

1DLC
424


ATOM
301
CE2
TRP
100
41.856
55.455
31.116
1.00
20.11

1DLC
425


ATOM
302
CE3
TRP
100
41.535
55.887
28.739
1.00
18.05

1DLC
426


ATOM
303
CH2
TRP
100
41.287
56.150
30.079
1.00
18.97

1DLC
427


ATOM
304
N
PRO
101
44.702
49.859
25.738
1.00
35.80

1DLC
428


ATOM
305
CA
PRO
101
45.347
49.557
24.455
1.00
37.30

1DLC
429


ATOM
306
C
PRO
101
44.651
50.132
23.217
1.00
38.37

1DLC
430


ATOM
307
O
PRO
101
45.309
50.557
22.271
1.00
39.64

1DLC
431


ATOM
308
CB
PRO
101
45.322
48.034
24.431
1.00
38.85

1DLC
432


ATOM
309
CG
PRO
101
44.017
47.726
25.088
1.00
35.28

1DLC
433


ATOM
310
CD
PRO
101
44.032
48.658
26.274
1.00
36.12

1DLC
434


ATOM
311
N
SER
102
43.322
50.129
23.227
1.00
40.19

1DLC
435


ATOM
312
CA
SER
102
42.514
50.620
22.105
1.00
41.68

1DLC
436


ATOM
313
C
SER
102
41.097
50.916
22.592
1.00
41.86

1DLC
437


ATOM
314
O
SER
102
40.831
50.852
23.769
1.00
41.66

1DLC
438


ATOM
315
CB
SER
102
42.439
49.547
21.019
1.00
43.16

1DLC
439


ATOM
316
OG
SER
102
41.925
48.330
21.556
1.00
45.57

1DLC
440


ATOM
317
N
GLU
103
40.178
51.206
21.674
1.00
41.50

1DLC
441


ATOM
318
CA
GLU
103
38.800
51.482
22.080
1.00
43.73

1DLC
442


ATOM
319
C
GLU
103
37.989
50.207
22.334
1.00
41.43

1DLC
443


ATOM
320
O
GLU
103
36.916
50.251
22.937
1.00
40.77

1DLC
444


ATOM
321
CB
GLU
103
38.078
52.403
21.076
1.00
48.24

1DLC
445


ATOM
322
CG
GLU
103
37.564
51.764
19.782
1.00
56.59

1DLC
446


ATOM
323
CD
GLU
103
38.656
51.448
18.766
1.00
63.51

1DLC
447


ATOM
324
OE1
GLU
103
39.739
52.096
18.786
1.00
66.38

1DLC
448


ATOM
325
OE2
GLU
103
38.417
50.544
17.931
1.00
65.54

1DLC
449


ATOM
326
N
ASP
104
38.544
49.065
21.947
1.00
40.07

1DLC
450


ATOM
327
CA
ASP
104
37.856
47.791
22.132
1.00
41.15

1DLC
451


ATOM
328
C
ASP
104
37.437
47.481
23.572
1.00
38.99

1DLC
452


ATOM
329
O
ASP
104
36.282
47.118
23.816
1.00
39.97

1DLC
453


ATOM
330
CB
ASP
104
38.674
46.634
21.543
1.00
44.04

1DLC
454


ATOM
331
CG
ASP
104
38.713
46.656
20.016
1.00
50.06

1DLC
455


ATOM
332
OD1
ASP
104
37.649
46.852
19.375
1.00
53.14

1DLC
456


ATOM
333
OD2
ASP
104
39.811
46.468
19.454
1.00
53.68

1DLC
457


ATOM
334
N
PRO
105
38.351
47.651
24.551
1.00
36.35

1DLC
458


ATOM
335
CA
PRO
105
37.984
47.364
25.944
1.00
34.16

1DLC
459


ATOM
336
C
PRO
105
36.845
48.263
26.449
1.00
33.17

1DLC
460


ATOM
337
O
PRO
105
35.899
47.794
27.069
1.00
31.65

1DLC
461


ATOM
338
CB
PRO
105
39.286
47.640
26.703
1.00
32.33

1DLC
462


ATOM
339
CG
PRO
105
40.336
47.374
25.695
1.00
32.70

1DLC
463


ATOM
340
CD
PRO
105
39.773
48.023
24.464
1.00
33.69

1DLC
464


ATOM
341
N
TRP
106
36.933
49.548
26.127
1.00
30.91

1DLC
465


ATOM
342
CA
TRP
106
35.928
50.519
26.543
1.00
31.51

1DLC
466


ATOM
343
C
THP
106
34.573
50.226
25.925
1.00
30.83

1DLC
467


ATOM
344
O
TRP
106
33.539
50.353
26.572
1.00
31.34

1DLC
468


ATOM
345
CB
TRP
106
36.404
51.928
26.200
1.00
30.77

1DLC
469


ATOM
346
CG
TRP
106
37.688
52.230
26.890
1.00
31.17

1DLC
470


ATOM
347
CD1
TRP
106
38.940
52.165
26.356
1.00
28.67

1DLC
471


ATOM
348
CD2
TRP
106
37.858
52.537
28.277
1.00
31.01

1DLC
472


ATOM
349
NE1
TRP
106
39.879
52.396
27.327
1.00
27.96

1DLC
473


ATOM
350
CE2
TRP
106
39.245
52.629
28.517
1.00
29.45

1DLC
474


ATOM
351
CE3
TRP
106
36.971
52.737
29.346
1.00
32.12

1DLC
475


ATOM
352
CE2
TRP
106
39.771
52.912
29.781
1.00
31.59

1DLC
476


ATOM
353
CZ3
TRP
106
37.495
53.019
30.607
1.00
33.16

1DLC
477


ATOM
354
CH2
TRP
106
38.884
53.103
30.811
1.00
31.59

1DLC
478


ATOM
355
N
LYS
107
34.588
49.786
24.678
1.00
33.17

1DLC
479


ATOM
356
CA
LYS
107
33.356
49.445
23.979
1.00
35.51

1DLC
480


ATOM
357
C
LYS
107
32.718
48.208
24.618
1.00
31.75

1DLC
481


ATOM
358
O
LYS
107
31.499
48.136
24.818
1.00
27.83

1DLC
482


ATOM
359
CB
LYS
107
33.674
49.188
22.506
1.00
40.04

1DLC
483


ATOM
360
CG
LYS
107
32.519
49.475
21.568
1.00
49.75

1DLC
484


ATOM
361
CD
LYS
107
33.032
49.919
20.204
1.00
56.89

1DLC
485


ATOM
362
CE
LYS
107
34.066
48.945
19.643
1.00
62.13

1DLC
486


ATOM
363
NZ
LYS
107
34.425
49.301
18.238
1.00
68.80

1DLC
487


ATOM
364
N
ALA
108
33.574
47.276
25.055
1.00
29.83

1DLC
488


ATOM
365
CA
ALA
108
33.160
46.045
25.720
1.00
28.62

1DLC
489


ATOM
366
C
ALA
108
32.569
46.312
27.115
1.00
29.18

1DLC
490


ATOM
367
O
ALA
108
31.652
45.598
27.559
1.00
28.23

1DLC
491


ATOM
368
CB
ALA
108
34.344
45.083
25.810
1.00
27.06

1DLC
492


ATOM
369
N
PHE
109
33.092
47.327
27.806
1.00
27.51

1DLC
493


ATOM
370
CA
PHE
109
32.589
47.701
29.129
1.00
26.94

1DLC
494


ATOM
371
C
PHE
109
31.193
48.301
29.013
1.00
27.69

1DLC
495


ATOM
372
O
PHE
109
30.338
48.104
29.876
1.00
29.41

1DLC
496


ATOM
373
CB
PHE
109
33.525
48.703
29.805
1.00
27.56

1DLC
497


ATOM
374
CG
PHE
109
34.672
48.064
30.528
1.00
32.09

1DLC
498


ATOM
375
CD1
PHE
109
34.465
46.954
31.344
1.00
33.41

1DLC
499


ATOM
376
CD2
PHE
109
35.962
48.566
30.396
1.00
32.21

1DLC
500


ATOM
377
CE1
PHE
109
35.523
46.351
32.018
1.00
34.60

1DLC
501


ATOM
378
CE2
PHE
109
37.025
47.972
31.065
1.00
34.23

1DLC
502


ATOM
379
CZ
PHE
109
36.805
46.860
31.879
1.00
34.84

1DLC
503


ATOM
380
N
MET
110
30.970
49.047
27.942
1.00
26.88

1DLC
504


ATOM
381
CA
MET
110
29.671
49.653
27.713
1.00
29.57

1DLC
505


ATOM
382
C
MET
110
28.666
48.544
27.402
1.00
31.10

1DLC
506


ATOM
383
O
MET
110
27.614
48.442
28.038
1.00
30.88

1DLC
507


ATOM
384
CB
MET
110
29.751
50.664
26.564
1.00
29.18

1DLC
508


ATOM
385
CG
MET
110
30.604
51.894
26.869
1.00
28.37

1DLC
509


ATOM
386
SD
MET
110
30.715
53.039
25.473
1.00
32.63

1DLC
510


ATOM
387
CE
MET
110
31.965
54.148
26.035
1.00
35.77

1DLC
511


ATOM
388
N
GLU
111
29.033
47.672
26.467
1.00
33.04

1DLC
512


ATOM
389
CA
GLU
111
28.179
46.553
26.078
1.00
33.48

1DLC
513


ATOM
390
C
GLU
111
27.885
45.632
27.257
1.00
31.71

1DLC
514


ATOM
391
O
GLU
111
26.801
45.054
27.338
1.00
30.92

1DLC
515


ATOM
392
CB
GLU
111
28.818
45.755
24.937
1.00
37.35

1DLC
516


ATOM
393
CG
GLU
111
28.863
46.510
23.607
1.00
45.28

1DLC
517


ATOM
394
CD
GLU
111
29.578
45.753
22.491
1.00
48.00

1DLC
518


ATOM
395
OE1
GLU
111
29.969
44.577
22.690
1.00
52.24

1DLC
519


ATOM
396
OE2
GLU
111
29.755
46.350
21.407
1.00
49.92

1DLC
520


ATOM
397
N
GLN
112
28.839
45.526
28.183
1.00
30.24

1DLC
521


ATOM
398
CA
GLN
112
28.671
44.682
29.368
1.00
28.56

1DLC
522


ATOM
399
C
GLN
112
27.431
45.053
30.182
1.00
28.06

1DLC
523


ATOM
400
O
GLN
112
26.565
44.277
30.454
1.00
29.19

1DLC
524


ATOM
401
CB
GLN
112
29.896
44.760
30.280
1.00
26.24

1DLC
525


ATOM
402
CG
GLN
112
29.763
43.882
31.517
1.00
27.12

1DLC
526


ATOM
403
CD
GLN
112
30.677
44.295
32.644
1.00
27.16

1DLC
527


ATOM
404
OE1
GLN
112
31.050
45.456
32.767
1.00
27.74

1DLC
528


ATOM
405
NE2
GLN
112
31.032
43.348
33.484
1.00
29.40

1DLC
529


ATOM
406
N
VAL
113
27.337
46.325
30.560
1.00
24.97

1DLC
530


ATOM
407
CA
VAL
113
26.201
46.764
31.349
1.00
23.68

1DLC
531


ATOM
408
C
VAL
113
24.932
46.792
30.519
1.00
24.60

1DLC
532


ATOM
409
O
VAL
113
23.853
46.539
31.031
1.00
27.38

1DLC
533


ATOM
410
CB
VAL
113
26.462
48.114
32.003
1.00
20.75

1DLC
534


ATOM
411
CG1
VAL
113
25.401
48.398
33.048
1.00
16.74

1DLC
535


ATOM
412
CG2
VAL
113
27.846
48.106
32.642
1.00
21.83

1DLC
536


ATOM
413
N
GLU
114
25.060
47.071
29.228
1.00
28.20

1DLC
537


ATOM
414
CA
GLU
114
23.894
47.081
28.351
1.00
27.34

1DLC
538


ATOM
415
C
GLU
114
23.268
45.681
28.368
1.00
27.33

1DLC
539


ATOM
416
O
GLU
114
22.048
45.527
26.410
1.00
27.26

1DLC
540


ATOM
417
CB
GLU
114
24.305
47.455
26.929
1.00
27.02

1DLC
541


ATOM
418
CG
GLU
114
24.757
48.893
26.776
1.00
29.51

1DLC
542


ATOM
419
CD
GLU
114
25.075
49.250
25.338
1.00
29.59

1DLC
543


ATOM
420
OE1
GLU
114
25.765
48.464
24.654
1.00
33.56

1DLC
544


ATOM
421
OE2
GLU
114
24.629
50.319
24.883
1.00
30.80

1DLC
545


ATOM
422
N
ALA
115
24.123
44.667
28.384
1.00
25.38

1DLC
546


ATOM
423
CA
ALA
115
23.700
43.276
26.425
1.00
23.38

1DLC
547


ATOM
424
C
ALA
115
22.994
42.964
29.735
1.00
24.92

1DLC
548


ATOM
425
O
ALA
115
21.939
42.357
29.731
1.00
30.01

1DLC
549


ATOM
426
CB
ALA
115
24.892
42.357
28.248
1.00
23.08

1DLC
550


ATOM
427
N
LEU
116
23.584
43.381
30.850
1.00
25.64

1DLC
551


ATOM
428
CA
LEU
116
23.008
43.153
32.179
1.00
26.66

1DLC
552


ATOM
429
C
LEU
116
21.688
43.895
32.397
1.00
27.99

1DLC
553


ATOM
430
O
LEU
116
20.761
43.382
33.023
1.00
29.24

1DLC
554


ATOM
431
CB
LEU
116
23.992
43.598
33.270
1.00
25.03

1DLC
555


ATOM
432
CO
LEU
116
25.261
42.770
33.501
1.00
28.01

1DLC
556


ATOM
433
CD1
LEU
116
26.257
43.525
34.380
1.00
26.20

1DLC
557


ATOM
434
CD2
LEU
116
24.890
41.442
34.132
1.00
27.91

1DLC
558


ATOM
435
N
MET
117
21.614
45.109
31.873
1.00
28.41

1DLC
559


ATOM
436
CA
MET
117
20.442
45.957
32.032
1.00
30.17

1DLC
560


ATOM
437
C
MET
117
19.390
45.825
30.934
1.00
31.82

1DLC
561


ATOM
438
O
MET
117
18.252
46.256
31.102
1.00
31.84

1DLC
562


ATOM
439
CB
MET
117
20.903
47.408
32.099
1.00
30.05

1DLC
563


ATOM
440
CG
MET
117
20.528
48.129
33.361
1.00
31.75

1DLC
564


ATOM
441
SD
MET
117
20.999
47.259
34.847
1.00
32.52

1DLC
565


ATOM
442
CE
MET
117
19.682
47.817
35.885
1.00
24.44

1DLC
566


ATOM
443
N
ASP
118
19.776
45.223
29.818
1.00
33.29

1DLC
567


ATOM
444
CA
ASP
118
18.894
45.073
28.666
1.00
37.23

1DLC
568


ATOM
445
C
ASP
118
18.412
46.445
28.203
1.00
37.19

1DLC
569


ATOM
446
O
ASP
118
17.225
46.683
27.979
1.00
37.25

1DLC
570


ATOM
447
CB
ASP
118
17.716
44.144
26.956
1.00
42.38

1DLC
571


ATOM
448
CG
ASP
118
17.205
43.450
27.697
1.00
47.50

1DLC
572


ATOM
449
OD1
ASP
118
18.027
42.797
27.009
1.00
50.29

1DLC
573


ATOM
450
OD2
ASP
118
15.993
43.564
27.392
1.00
50.50

1DLC
574


ATOM
451
N
GLN
119
19.372
47.355
28.106
1.00
39.11

1DLC
575


ATOM
452
CA
GLN
119
19.151
48.722
27.660
1.00
39.37

1DLC
576


ATOM
453
C
GLN
119
20.371
49.116
26.849
1.00
39.51

1DLC
577


ATOM
454
O
GLN
119
21.416
48.478
26.946
1.00
41.09

1DLC
578


ATOM
455
CB
GLN
119
19.029
49.674
28.841
1.00
41.10

1DLC
579


ATOM
456
CO
GLN
119
17.784
49.520
29.657
1.00
47.05

1DLC
580


ATOM
457
CD
GLN
119
17.628
50.660
30.637
1.00
52.24

1DLC
581


ATOM
458
OE1
GLN
119
17.745
50.484
31.851
1.00
54.31

1DLC
582


ATOM
459
NE2
GLN
119
17.385
51.850
30.111
1.00
55.17

1DLC
583


ATOM
460
N
LYS
120
20.250
50.179
26.066
1.00
41.11

1DLC
584


ATOM
461
CA
LYS
120
21.361
50.647
25.250
1.00
32.74

1DLC
585


ATOM
462
C
LYS
120
21.613
52.129
25.433
1.00
38.08

1DLC
586


ATOM
463
O
LYS
120
20.710
52.890
25.773
1.00
39.76

1DLC
587


ATOM
464
CE
LYS
120
21.100
50.341
23.779
1.00
41.32

1DLC
588


ATOM
465
CG
LYS
120
21.203
48.862
23.444
1.00
47.56

1DLC
589


ATOM
466
CD
LYS
120
20.881
48.608
21.991
1.00
54.97

1DLC
590


ATOM
467
CE
LYS
120
21.147
47.160
21.615
1.00
59.79

1DLC
591


ATOM
468
NZ
LYS
120
20.761
46.901
20.190
1.00
67.72

1DLC
592


ATOM
469
N
ILE
121
22.863
52.524
25.265
1.00
37.13

1DLC
593


ATOM
470
CA
ILE
121
23.241
53.921
25.385
1.00
37.29

1DLC
594


ATOM
471
C
ILE
121
22.939
54.602
24.039
1.00
38.92

1DLC
595


ATOM
472
O
ILE
121
23.157
54.009
22.977
1.00
39.34

1DLC
596


ATOM
473
CB
ILE
121
24.749
54.063
25.715
1.00
34.38

1DLC
597


ATOM
474
CG1
ILE
121
25.097
53.244
26.961
1.00
35.00

1DLC
598


ATOM
475
CG2
ILE
121
25.089
55.514
25.969
1.00
34.52

1DLC
599


ATOM
476
CD1
ILE
121
26.580
53.116
27.247
1.00
31.52

1DLC
600


ATOM
477
N
ALA
122
22.383
55.811
24.081
1.00
37.83

1DLC
601


ATOM
478
CA
ALA
122
22.083
56.545
22.854
1.00
37.13

1DLC
602


ATOM
479
C
ALA
122
23.388
56.682
22.075
1.00
38.77

1DLC
603


ATOM
480
O
ALA
122
24.391
57.131
22.629
1.00
42.15

1DLC
604


ATOM
481
CR
ALA
122
21.528
57.909
23.169
1.00
31.82

1DLC
605


ATOM
482
N
ASP
123
23.366
56.275
20.808
1.00
40.84

1DLC
606


ATOM
483
CA
ASP
123
24.588
56.342
19.971
1.00
42.51

1DLC
607


ATOM
484
C
ASP
123
25.452
57.587
20.115
1.00
40.46

1DLC
608


ATOM
485
O
ASP
123
26.671
57.482
20.157
1.00
37.07

1DLC
609


ATOM
486
CB
ASP
123
24.239
56.135
18.501
1.00
51.37

1DLC
610


ATOM
487
CG
ASP
123
24.397
54.690
18.069
1.00
59.26

1DLC
611


ATOM
488
OD1
ASP
123
25.508
54.135
18.240
1.00
63.85

1DLC
612


ATOM
489
OD2
ASP
123
23.414
54.107
17.560
1.00
65.85

1DLC
613


ATOM
490
N
TYR
124
24.821
58.756
20.210
1.00
41.62

1DLC
614


ATOM
491
CA
TYR
124
25.554
60.015
20.361
1.00
41.32

1DLC
615


ATOM
492
C
TYR
124
26.390
59.997
21.645
1.00
41.19

1DLC
616


ATOM
493
O
TYR
124
27.575
60.341
21.633
1.00
44.09

1DLC
617


ATOM
494
CS
TYR
124
24.590
61.220
20.349
1.00
41.20

1DLC
618


ATOM
495
CO
TYR
124
23.913
51.533
21.674
1.00
45.22

1DLC
619


ATOM
496
CD1
TYR
124
24.551
62.322
22.634
1.00
46.84

1DLC
620


ATOM
497
CD2
TYR
124
22.643
61.038
21.972
1.00
46.22

1DLC
621


ATOM
498
CE1
TYR
124
23.948
62.606
23.856
1.00
48.97

1DLC
622


ATOM
499
CE2
TYR
124
22.025
61.320
23.199
1.00
48.29

1DLC
623


ATOM
500
CZ
TYR
124
22.686
62.105
24.135
1.00
50.39

1DLC
624


ATOM
501
OH
TYR
124
22.109
62.394
25.353
1.00
51.34

1DLC
625


ATOM
502
N
ALA
125
25.775
59.545
22.738
1.00
38.41

1DLC
626


ATOM
503
CA
ALA
125
26.442
59.468
24.033
1.00
36.03

1DLC
627


ATOM
504
C
ALA
125
27.544
58.411
24.021
1.00
35.18

1DLC
628


ATOM
505
O
ALA
125
28.569
58.567
24.676
1.00
36.66

1DLC
629


ATOM
506
CB
ALA
125
25.429
59.169
25.127
1.00
36.03

1DLC
630


ATOM
507
N
LYS
126
27.332
57.349
23.253
1.00
34.60

1DLC
631


ATOM
508
CA
LYS
126
28.300
56.259
23.132
1.00
35.76

1DLC
632


ATOM
509
C
LYS
126
29.519
56.726
22.325
1.00
36.46

1DLC
633


ATOM
510
O
LYS
126
30.669
56.513
22.719
1.00
36.95

1DLC
634


ATOM
511
CE
LYS
126
27.621
55.071
22.445
1.00
38.14

1DLC
635


ATOM
512
CG
LYS
126
28.249
53.708
22.678
1.00
39.63

1DLC
636


ATOM
513
CD
LYS
126
27.180
52.619
22.514
1.00
43.72

1DLC
637


ATOM
514
CE
LYS
126
27.763
51.210
22.428
1.00
45.37

1DLC
638


ATOM
515
NZ
LYS
126
28.477
50.752
23.655
1.00
48.58

1DLC
639


ATOM
516
N
ASN
127
29.258
57.409
21.215
1.00
38.31

1DLC
640


ATOM
517
CA
ASN
127
30.321
57.915
20.353
1.00
39.67

1DLC
641


ATOM
518
C
ASN
127
31.184
58.966
21.032
1.00
38.46

1DLC
642


ATOM
519
O
ASN
127
32.404
58.932
20.904
1.00
39.48

1DLC
643


ATOM
520
CB
ANN
127
29.749
58.479
19.051
1.00
42.71

1DLC
644


ATOM
521
CG
ASN
127
29.088
57.415
18.198
1.00
46.61

1DLC
645


ATOM
522
OD1
ASN
127
28.081
57.675
17.543
1.00
52.98

1DLC
646


ATOM
523
ND2
ASN
127
29.648
56.209
18.198
1.00
42.83

1DLC
647


ATOM
524
N
LYS
128
30.563
59.911
21.733
1.00
38.09

1DLC
648


ATOM
525
CA
LYS
128
31.349
60.929
22.415
1.00
39.08

1DLC
649


ATOM
526
C
LYS
128
32.237
60.300
23.472
1.00
38.69

1DLC
650


ATOM
527
O
LYS
128
33.415
60.642
23.577
1.00
42.45

1DLC
651


ATOM
528
CS
LYS
128
30.495
62.006
23.071
1.00
41.87

1DLC
652


ATOM
529
CG
LYS
128
31.380
62.951
23.800
1.00
46.08

1DLC
653


ATOM
530
CD
LYS
128
30.689
64.221
24.295
1.00
49.62

1DLC
654


ATOM
531
CE
LYS
128
31.726
65.260
24.666
1.00
47.91

1DLC
655


ATOM
532
NZ
LYS
128
32.699
65.442
23.547
1.00
50.26

1DLC
656


ATOM
533
N
ALA
129
31.668
59.381
24.248
1.00
34.82

1DLC
657


ATOM
514
CA
ALA
129
32.420
58.691
25.287
1.00
33.08

1DLC
658


ATOM
535
C
ALA
129
33.673
58.059
24.676
1.00
32.09

1DLC
659


ATOM
536
O
ALA
129
34.793
58.278
25.150
1.00
31.18

1DLC
660


ATOM
537
CB
ALA
129
31.552
57.628
25.953
1.00
30.56

1DLC
661


ATOM
538
N
LEU
130
33.486
57.327
21.582
1.00
32.74

1DLC
662


ATOM
539
CA
LEO
130
34.600
56.673
22.903
1.00
30.32

1DLC
663


ATOM
540
C
LEU
130
35.640
57.669
22.407
1.00
31.27

1DLC
664


ATOM
541
O
LEU
130
36.849
57.410
22.474
1.00
31.13

1DLC
665


ATOM
542
CB
LEU
130
34.081
55.613
21.755
1.00
29.76

1DLC
666


ATOM
543
CG
LEO
130
33.435
54.489
22.182
1.00
30.23

1DLC
667


ATOM
544
CD1
LEU
130
32.732
53.832
21.000
1.00
30.62

1DLC
668


ATOM
545
CD2
LEU
130
34.499
53.559
22.764
1.00
26.30

1DLC
669


ATOM
546
N
ALA
131
35.166
58.829
21.960
1.00
32.32

1DLC
670


ATOM
547
CA
ALA
131
16.046
59.883
21.460
1.00
32.99

1DLC
671


ATOM
548
C
ALA
131
36.929
60.416
22.584
1.00
34.16

1DLC
672


ATOM
549
O
ALA
131
38.145
60.515
22.427
1.00
37.33

1DLC
673


ATOM
550
CR
ALA
131
35.229
61.008
20.847
1.00
31.10

1DLC
674


ATOM
551
N
GLU
132
36.318
60.735
23.725
1.00
34.14

1DLC
575


ATOM
552
CA
CLU
132
37.054
61.234
24.891
1.00
31.85

1DLC
676


ATOM
553
C
GLU
132
38.128
60.232
25.296
1.00
30.73

1DLC
677


ATOM
554
O
CICU
132
39.279
60.598
25.536
1.00
30.23

1DLC
678


ATOM
556
CB
GLU
132
36.109
61.439
26.072
1.00
28.74

1DLC
679


ATOM
556
CG
GLU
132
35.049
62.483
25.842
1.00
33.99

1DLC
680


ATOM
557
CD
GLU
132
35.617
63.884
25.722
1.00
40.12

1DLC
681


ATOM
558
OE1
GLU
132
36.787
64.104
26.104
1.00
41.36

1DLC
682


ATOM
659
OE2
GLU
132
34.882
64.778
25.251
1.00
46.52

1DLC
683


ATOM
560
N
LEU
133
37.739
58.961
25.320
1.00
31.50

1DLC
684


ATOM
561
CA
LEU
133
30.627
57.866
25.692
1.00
32.60

1DLC
685


ATOM
562
C
LEU
133
39.845
57.712
24.785
1.00
34.20

1DLC
686


ATOM
563
O
LEU
133
40.930
57.388
25.261
1.00
34.43

1DLC
687


ATOM
564
CB
LEU
133
37.833
56.561
25.795
1.00
30.47

1DLC
688


ATOM
565
CG
LEU
133
36.896
56.525
27.009
1.00
30.33

1DLC
689


ATOM
566
CD1
LEO
133
35.766
55.538
26.796
1.00
26.58

1DLC
690


ATOM
567
CD2
LEU
133
37.693
56.206
28.271
1.00
24.25

1DLC
691


ATOM
568
N
GLN
134
39.679
57.952
23.486
1.00
37.63

1DLC
692


ATOM
569
CA
GLN
134
40.812
57.866
22.564
1.00
39.17

1DLC
693


ATOM
570
C
GLN
134
41.814
58.949
22.945
1.00
36.45

1DLC
694


ATOM
571
O
GLN
134
43.015
58.701
23.038
1.00
38.66

1DLC
695


ATOM
572
CB
GLN
134
40.363
58.083
21.119
1.00
47.75

1DLC
696


ATOM
573
CG
GLN
134
39.344
57.074
20.614
1.00
61.82

1DLC
697


ATOM
574
CD
GLN
134
39.792
55.634
20.821
1.00
70.74

1DLC
698


ATOM
575
OE1
GLN
134
40.513
55.060
19.996
1.00
73.31

1DLC
699


ATOM
576
NE2
GLN
134
39.359
55.041
21.928
1.00
73.58

1DLC
700


ATOM
577
N
GLY
135
41.301
60.147
23.207
1.00
32.99

1DLC
701


ATOM
578
CA
GLY
135
42.156
61.255
23.599
1.00
32.54

1DLC
702


ATOM
579
C
GLY
135
42.871
61.024
24.921
1.00
32.17

1DLC
703


ATOM
580
O
GLY
135
44.039
61.378
25.080
1.00
34.18

1DLC
704


ATOM
581
N
LEU
136
42.160
80.445
25.881
1.00
30.44

1DLC
705


ATOM
582
CA
LEU
136
42.729
60.151
27.190
1.00
30.39

1DLC
706


ATOM
583
C
LEU
136
43.818
59.084
27.081
1.00
31.99

1DLC
707


ATOM
584
O
LEU
136
44.794
59.096
27.828
1.00
32.33

1DLC
708


ATOM
585
CB
LEU
136
41.837
59.668
28.141
1.00
28.24

1DLC
709


ATOM
586
CG
LEU
136
40.578
60.685
28.552
1.00
25.44

1DLC
710


ATOM
587
CD1
LEU
136
39.432
59.977
29.232
1.00
20.57

1DLC
711


ATOM
588
CD2
LEU
136
41.202
81.714
29.468
1.00
23.94

1DLC
712


ATOM
599
N
GLN
137
43.644
58.159
26.144
1.00
34.65

1DLC
713


ATOM
590
CA
GLN
137
44.612
57.091
25.937
1.00
36.83

1DLC
714


ATOM
591
C
GLN
137
45.968
57.692
25.570
1.00
37.51

1DLC
715


ATOM
592
O
GLN
137
46.980
57.410
26.221
1.00
35.29

1DLC
716


ATOM
593
CB
GLN
137
44.138
56.152
24.829
1.00
39.14

1DLC
717


ATOM
594
CG
GLN
137
44.992
54.905
24.664
1.00
43.17

1DLC
718


ATOM
595
CD
GLN
137
44.607
54.094
23.445
1.00
45.19

1DLC
719


ATOM
596
OE1
GLN
137
43.460
54.127
22.989
1.00
47.54

1DLC
720


ATOM
597
NE2
GLN
137
45.562
53.355
22.911
1.00
46.02

1DLC
721


ATOM
599
N
ASN
138
45.970
58.561
24.561
1.00
37.22

1DLC
722


ATOM
599
CA
ASN
138
47.195
59.219
24.119
1.00
39.24

1DLC
723


ATOM
600
C
ASN
138
47.872
59.935
25.281
1.00
36.46

1DLC
724


ATOM
601
O
ASN
138
49.078
59.799
25.478
1.00
36.61

1DLC
725


ATOM
602
CB
ANN
138
46.898
60.203
22.989
1.00
43.17

1DLC
776


ATOM
603
CG
ASN
138
46.319
59.516
21.164
1.00
50.90

1DLC
727


ATOM
604
OD
ASN
138
46.471
58.303
21.580
1.00
54.32

1DLC
728


ATOM
605
ND2
ASN
138
45.640
60.283
20.923
1.00
51.88

1DLC
729


ATOM
606
N
ASN
139
47.079
60.639
26.085
1.00
33.80

1DLC
730


ATOM
607
CA
ASN
139
47.601
61.358
27.247
1.00
31.83

1DLC
731


ATOM
808
C
ASN
139
48.263
60.412
28.233
1.00
30.17

1DLC
732


ATOM
609
O
ASN
139
49.350
60.691
28.733
1.00
29.01

1DLC
733


ATOM
610
CB
ASN
139
46.485
62.115
27.969
1.00
32.59

1DLC
734


ATOM
611
CG
ASN
139
45.928
63.270
27.154
1.00
37.15

1DLC
735


ATOM
612
OD1
ASN
139
45.081
64.014
27.634
1.00
42.84

1DLC
736


ATOM
613
ND2
ASN
139
46.392
63.425
25.926
1.00
35.37

1DLC
737


ATOM
614
N
VAL
140
47.611
59.281
28.493
1.00
30.85

1DLC
738


ATOM
615
CA
VAL
140
48.141
58.301
29.436
1.00
35.20

1DLC
739


ATOM
616
C
VAL
140
49.421
57.652
28.911
1.00
35.66

1DLC
740


ATOM
617
O
VAL
140
50.406
57.516
29.645
1.00
36.30

1DLC
741


ATOM
618
CB
VAL
140
47.097
57.202
29.794
1.00
33.23

1DLC
742


ATOM
619
CG
TVAL
140
47.596
56.370
30.970
1.00
30.81

1DLC
743


ATOM
620
CG2
VAL
140
45.772
57.829
30.158
1.00
34.27

1DLC
744


ATOM
621
N
GLU
141
49.412
57.280
27.635
1.00
36.48

1DLC
745


ATOM
622
CA
GLU
141
50.575
56.655
27.016
1.00
37.87

1DLC
746


ATOM
623
C
GLU
141
51.777
57.606
26.989
1.00
36.94

1DLC
747


ATOM
624
O
GLU
141
52.868
57.250
27.451
1.00
36.22

1DLC
748


ATOM
625
CB
GLU
141
50.223
56.142
25.613
1.00
39.44

1DLC
749


ATOM
626
CG
GLU
141
49.194
55.010
25.647
1.00
46.15

1DLC
750


ATOM
627
CD
GLU
141
48.815
54.460
24.273
1.00
50.50

1DLC
751


ATOM
628
OE1
GLU
141
48.932
55.189
23.255
1.00
48.49

1DLC
752


ATOM
629
OE2
GLU
141
48.377
53.286
24.225
1.00
52.05

1DLC
753


ATOM
630
N
ASP
142
51.562
58.831
26.514
1.00
34.71

1DLC
754


ATOM
631
CA
ASP
142
52.633
59.819
26.462
1.00
33.53

1DLC
755


ATOM
632
C
ASP
142
53.214
59.998
27.849
1.00
32.09

1DLC
756


ATOM
633
O
ASP
142
54.434
60.066
28.019
1.00
33.76

1DLC
757


ATOM
634
CS
ASP
142
52.124
61.168
25.943
1.00
34.47

1DLC
758


ATOM
635
CG
ASP
142
51.806
61.150
24.452
1.00
37.60

1DLC
759


ATOM
636
OD1
ASP 
142
52.150
60.158
23.765
1.00
37.44

1DLC
760


ATOM
637
OD2
ASP
142
51.204
62.135
23.967
1.00
37.76

1DLC
761


ATOM
638
N
TYR
143
52.336
60.020
28.847
1.00
29.85

1DLC
762


ATOM
639
CA
TYR 
143
52.770
60.160
30.228
1.00
31.12

1DLC
763


ATOM
640
C
TYR
143
53.619
59.010
30.741
1.00
31.96

1DLC
764


ATOM
641
O
TYR
143
54.655
59.221
31.373
1.00
29.33

1DLC
765


ATOM
642
CS 
TYR
143
51.569
60.394
31.162
1.00
29.85

1DLC
766


ATOM
643
CG
TYR
143
51.951
60.326
32.627
1.00
28.37

1DLC
767


ATOM
644
CD1
TYR 
143
52.705
61.347
33.220
1.00
27.51

1DLC
766


ATOM
645
CD2
TYR 
143
51.631
59.207
33.397
1.00
26.05

1DLC
769


ATOM
646
CE1
TYR
143
53.135
61.251
34.532
1.00
25.76

1DLC
770


ATOM
547
CE2
TYR 
143
52.057
59.101
34.716
1.00
26.39

1DLC
771


ATOM
648
CZ
TYR
143
52.809
60.124
35.274
1.00
27.82

1DLC
772


ATOM
649
OH 
TYR
143
53.252
60.012
36.569
1.00
30.91

1DLC
773


ATOM
650
N
VAL 
144
53.156
57.784
30.499
1.00
34.31

1DLC
774


ATOM
651
CA
VAL 
144
53.863
56.587
30.951
1.00
35.26

1DLC
775


ATOM
652
C
VAL 
144
55.239
56.440
30.316
1.00
36.56

1DLC
776


ATOM
653
O
VAL
144
56.205
56.111
31.008
1.00
37.15

1DLC
777


ATOM
654
CB
VAL
44
53.033
55.298
30.720
1.00
35.68

1DLC
778


ATOM
655
CG1
VAL
144
53.836
54.065
31.131
1.00
32.11

1DLC
779


ATOM
656
CG2
VAL
144
51.747
55.363
31.529
1.00
33.51

1DLC
780


ATOM
657
N
SER
145
55.341
56.599
29.011
1.00
37.88

1DLC
781


ATOM
658
CA
SER
145
56.642
56.601
28.332
1.00
38.87

1DLC
782


ATOM
659
C
SER
145
57.635
57.535
29.031
1.00
34.99

1DLC
783


ATOM
660
O
SER
145
58.720
57.117
29.437
1.00
38.01

1DLC
784


ATOM
651
CB
SER
145
56.534
56.951
26.834
1.00
39.91

1DLC
785


ATOM
662
OG 
SER
145
56.444
58.350
26.596
1.00
46.34

1DLC
786


ATOM
663
N
ALA
146
57.207
58.772
29.258
1.00
30.82

1DLC
787


ATOM
664
CA
ALA
146
58.031
59.761
29.931
1.00
30.30

1DLC
788


ATOM
665
C
ALA
146
58.359
59.340
31.364
1.00
31.85

1DLC
789


ATOM
660
O
ALA
146
59.509
59.426
31.790
1.00
35.45

1DLC
790


ATOM
667
CB
ALA 
146
57.345
61.123
29.915
1.00
27.74

1DLC
791


ATOM
668
N
LED
147
57.362
58.863
32.103
1.00
32.59

1DLC
792


ATOM
669
CA
LEO
147
57.595
58.432
33.477
1.00
32.81

1DLC
793


ATOM
670
C
LEO
147
58.607
57.297
33.490
1.00
33.53

1DLC
794


ATOM
671
O
LED
147
59.496
57.252
34.337
1.00
35.25

1DLC
795


ATOM
672
CB
LEO
147
56.300
57.968
34.150
1.00
32.39

1DLC
796


ATOM
673
CG
LEO
147
56.502
57.425
35.574
1.00
30.47

1DLC
797


ATOM
674
CD1
LEU 
147
57.043
58.522
36.480
1.00
29.60

1DLC
798


ATOM
675
CD2
LEO
147
55.204
56.866
36.129
1.00
32.87

1DLC
799


ATOM
676
N
SER
148
58.489
56.399
32.523
1.00
34.54

1DLC
800


ATOM
677
CA
SER
148
59.400
55.270
32.416
1.00
38.01

1DLC
801


ATOM
678
C
SER
148
60.844
55.766
32.240
1.00
38.45

1DLC
802


ATOM
679
O
SER 
148
61.767
55.311
32.931
1.00
38.67

1DLC
803


ATOM
680
CB
SER
148
58.993
54.398
31.237
1.00
41.71

1DLC
804


ATOM
681
OG 
SER
148
59.823
53.242
31.146
1.00
52.18

1DLC
605


ATOM
682
N
SER 
149
61.031
56.724
31.338
1.00
37.60

1DLC
806


ATOM
683
CA
SER
149
62.355
57.292
31.098
1.00
36.97

1DLC
807


ATOM
684
C
SER 
149
62.888
57.943
32.369
1.00
36.69

1DLC
808


ATOM
685
O
SER
149
64.015
57.693
32.768
1.00
40.93

1DLC
809


ATOM
686
CB
SER
149
62.317
58.329
29.968
1.00
40.27

1DLC
810


ATOM
687
OG 
SER
149
61.927
57.753
28.725
1.00
42.78

1DLC
811


ATOM
688
N
TRP
150
62.057
58.739
33.030
1.00
36.23

1DLC
812


ATOM
689
CA
TRP
150
62.458
59.417
34.260
1.00
35.43

1DLC
813


ATOM
690
C
TRP 
150
62.997
58.455
35.332
1.00
40.04

1DLC
814


ATOM
691
O
TRP 
150
64.055
58.695
35.912
1.00
41.77

1DLC
815


ATOM
692
CH 
TRP
150
61.296
60.237
34.813
1.00
29.63

1DLC
816


ATOM
693
CG
TRP
150
61.601
60.987
36.069
1.00
25.67

1DLC
817


ATOM
694
CD1
TRP 
150
61.510
60.519
37.346
1.00
25.82

1DLC
815


ATOM
695
CD2
TRP 
150
62.068
62.339
36.170
1.00
26.03

1DLC
819


ATOM
696
NE1
TRP
150
61.895
61.491
38.236
1.00
23.31

1DLC
820


ATOM
697
CE2
TRP
150
62.241
62.619
37.541
1.00
22.80

1DLC
321


ATOM
698
CE3
TRP
150
62.354
63.342
35.235
1.00
25.92

1DLC
822


ATOM
699
CZ2
TRP
150
62.687
63.857
38.001
1.00
25.85

1DLC
823


ATOM
700
CZ3
TRP
150
62.797
64.578
35.696
1.00
26.29

1DLC
824


ATOM
701
CH2
TRP
150
62.958
64.822
37.065
1.00
25.55

1DLC
825


ATOM
702
N
GLN
151
62.263
57.378
35.602
1.00
44.57

1DLC
826


ATOM
703
CA
GLN
151
62.681
56.396
36.602
1.00
48.28

1DLC
827


ATOM
704
C
GLN
151
64.013
55.747
36.227
1.00
50.95

1DLC
828


ATOM
705
O
GLN
151
64.902
55.586
37.061
1.00
50.37

1DLC
829


ATOM
706
CB
GLN
151
61.627
55.304
36.763
1.00
48.02

1DLC
830


ATOM
707
CO
GLN
151
60.751
55.460
37.990
1.00
51.89

1DLC
831


ATOM
708
CD
OLN
151
61.539
55.351
39.287
1.00
55.39

1DLC
832


ATOM
709
OE1
GLN
151
62.270
54.382
39.506
1.00
56.87

1DLC
833


ATOM
710
NE2
GLN
151
61.397
56.345
40.153
1.00
54.44

1DLC
834


ATOM
711
N
LYS
152
64.116
55.379
34.954
1.00
55.10

1DLC
835


ATOM
712
CA
LYS
152
65.296
54.729
34.388
1.00
59.98

1DLC
336


ATOM
713
C
LYS
152
66.545
55.624
34.404
1.00
62.63

1DLC
837


ATOM
714
O
LYS
152
67.645
55.172
34.734
1.00
63.39

1DLC
838


ATOM
715
CB
LYS
152
64.974
54.300
32.953
1.00
59.73

1DLC
839


ATOM
716
CG
LYS
152
65.960
53.357
32.101
1.00
62.85

1DLC
840


ATOM
717
CD
LYS
152
65.440
52.978
30.920
1.00
68.02

1DLC
841


ATOM
718
CE
LYS
152
66.367
52.023
30.168
1.00
69.39

1DLC
842


ATOM
719
NZ
LYS
152
65.842
51.764
28.785
1.00
68.57

1DLC
843


ATOM
720
N
ASN
153
66.367
55.891
34.044
1.00
64.53

1DLC
844


ATOM
721
CA
ASN
153
67.472
57.839
34.003
1.00
66.57

1DLC
845


ATOM
722
C
ASN
153
67.961
58.271
35.124
1.00
68.87

1DLC
846


ATOM
723
O
ASN
153
67.165
58.560
36.283
1.00
68.08

1DLC
847


ATOM
724
CB
ASN
153
67.097
59.057
33.153
1.00
67.50

1DLC
848


ATOM
725
CG
ASN
153
67.050
58.743
31.656
1.00
69.77

1DLC
849


ATOM
726
OD1
ASN
153
66.936
59.649
30.831
1.00
71.11

1DLC
850


ATOM
727
ND2
ASN
153
67.150
57.464
31.300
1.00
66.53

1DLC
851


ATOM
728
N
PRO
154
89.294
58.308
35.570
1.00
71.40

1DLC
852


ATOM
729
CA
PRO
154
69.934
58.697
36.830
1.00
71.82

1DLC
853


ATOM
730
C
PRO
154
69.610
60.141
37.198
1.00
72.79

1DLC
854


ATOM
731
O
PRO
154
69.311
60.961
36.324
1.00
73.90

1DLC
855


ATOM
732
CB
PRO
154
71.424
58.545
36.516
1.00
71.42

1DLC
856


ATOM
733
CG
PRO
154
71.450
57.498
35.443
1.00
71.51

1DLC
857


ATOM
734
CD
PRO
154
70.312
57.939
34.570
1.00
71.69

1DLC
858


ATOM
735
N
VAL
155
69.768
60.470
38.477
1.00
73.01

1DLC
859


ATOM
736
CA
VAL
155
69.491
61.818
38.977
1.00
73.15

1DLC
860


ATOM
737
C
VAL
155
70.486
62.875
38.445
1.00
75.28

1DLC
861


ATOM
738
O
VAL
155
70.723
63.903
39.077
1.00
75.71

1DLC
862


ATOM
739
CB
VAL
155
69.476
61.835
40.528
1.00
71.19

1DLC
863


ATOM
740
CG1
VAL
155
68.762
63.078
41.040
1.00
70.94

1DLC
864


ATOM
741
CG2
VAL
155
68.801
60.577
41.069
1.00
69.36

1DLC
865


ATOM
742
N
SER
156
71.065
62.602
37.280
1.00
77.11

1DLC
866


ATOM
743
CA
SER
156
72.021
63.495
36.635
1.00
78.87

1DLC
867


ATOM
744
C
SER
156
71.400
64.161
35.408
1.00
79.29

1DLC
668


ATOM
745
O
SER
156
71.396
65.386
35.299
1.00
82.25

1DLC
869


ATOM
746
CB
SER
156
73.261
62.709
36.206
1.00
80.07

1DLC
870


ATOM
747
OG
SER
16
72.912
61.680
35.287
1.00
82.66

1DLC
871


ATOM
748
N
SER 
157
70.853
63.352
34.500
1.00
76.97

1DLC
872


ATOM
749
CA
SER 
157
70.225
63.867
33.274
1.00
75.30

1DLC
873


ATOM
750
C
SER
157
68.956
64.689
33.534
1.00
72.28

1DLC
874


ATOM
751
O
SER 
157
68.296
65.162
32.599
1.00
72.55

1DLC
875


ATOM
752
CB
SER
157
69.896
62.715
32.317
1.00
78.07

1DLC
876


ATOM
753
OG
SER 
157
69.458
63.189
31.047
1.00
80.58

1DLC
877


ATOM
754
N
ARG
158
68.597
64.824
34.805
1.00
67.95

1DLC
878


ATOM
755
CA
ARG
158
67.422
65.585
35.193
1.00
62.74

1DLC
879


ATOM
756
C
ARG
158
67.736
67.076
35.191
1.00
59.17

1DLC
880


ATOM
757
O
ARG
158
68.229
67.636
36.170
1.00
60.26

1DLC
881


ATOM
758
CB
ARG
158
66.933
65.122
36.561
1.00
62.84

1DLC
882


ATOM
759
CG
ARG
158
66.524
63.677
36.539
1.00
64.01

1DLC
883


ATOM
760
CD
ARG
158
66.356
53.122
37.919
1.00
64.75

1DLC
884


ATOM
761
NE
ARG
158
66.051
61.699
37.848
1.00
67.56

1DLC
885


ATOM
762
CZ
ARG
158
65.636
60.970
38.879
1.00
71.03

1DLC
886


ATOM
763
NH1
ARG
158
65.479
61.529
40.079
1.00
70.73

1DLC
887


ATOM
764
NH2
ARG
158
65.372
59.678
38.706
1.00
73.39

1DLC
668


ATOM
765
N
ASN
159
67.500
67.692
34.045
1.00
52.90

1DLC
809


ATOM
766
CA
ASN
159
67.737
69.110
33.868
1.00
46.95

1DLC
890


ATOM
767
C
ASN
159
66.389
69.826
33.888
1.00
44.55

1DLC
891


ATOM
768
O
ASN
159
65.351
69.202
33.666
1.00
45.26

1DLC
892


ATOM
769
CB
ASN
159
68.435
69.331
32.532
1.00
45.92

1DLC
893


ATOM
770
CG
ASN
159
67.630
68.811
31.374
1.00
40.97

1DLC
894


ATOM
771
OD1
ASN
159
66.694
69.453
30.928
1.00
44.27

1DLC
895


ATOM
772
ND2
ASN
159
67.911
67.632
30.096
1.00
42.45

1DLC
896


ATOM
773
N
PRO
160
66.383
71.148
34.126
1.00
43.08

1DLC
697


ATOM
774
CA
PRO
160
65.129
71.908
34.161
1.00
40.97

1DLC
898


ATOM
775
C
PRO
160
64.253
71.635
32.942
1.00
40.72

1DLC
899


ATOM
776
O
PRO
160
63.033
71.541
33.039
1.00
43.29

1DLC
900


ATOM
777
CB
PRO
160
65.617
73.359
34.167
1.00
37.69

1DLC
901


ATOM
778
CG
PRO
160
66.883
73.275
34.935
1.00
38.08

1DLC
902


ATOM
779
CD
PRO
160
67.537
72.036
34.363
1.00
41.86

1DLC
903


ATOM
780
N
HIS
161
54.898
71.454
31.600
1.00
41.25

1DLC
904


ATOM
781
CA
HIS
161
64.199
71.210
10.551
1.00
41.19

1DLC
905


ATOM
782
C
HIS
161
63.401
69.905
30.481
1.00
38.76

1DLC
906


ATOM
783
O
HIS
161
62.324
69.880
29.901
1.00
40.73

1DLC
907


ATOM
704
CB
HIS
161
65.191
71.365
29.393
1.00
46.06

1DLC
900


ATOM
785
CG
HIS
161
64.907
70.490
28.220
1.00
51.42

1DLC
909


ATOM
786
ND1
HIS
161
63.840
70.697
27.171
1.00
53.89

1DLC
910


ATOM
787
CD2
HIS
161
65.564
69.405
27.743
1.00
54.97

1DLC
911


ATOM
788
CE1
HIS
161
63.851
69.775
26.428
1.00
57.18

1DLC
912


ATOM
789
NE2
1HIS
161
64.887
68.979
26.633
1.00
60.77

1DLC
913


ATOM
790
N
SER
162
63.927
68.824
31.048
1.00
37.14

1DLC
914


ATOM
791
CA
SER
162
63.201
67.547
31.031
1.00
37.50

1DLC
915


ATOM
792
C
SER
162
62.112
67.523
32.108
1.00
35.54

1DLC
916


ATOM
793
O
SER
162
61.074
66.881
31.944
1.00
35.11

1DLC
917


ATOM
794
CB
SER
162
64.147
66.347
31.188
1.00
35.89

1DLC
918


ATOM
795
OG
SER
162
64.975
66.468
32.332
1.00
43.72

1DLC
919


ATOM
796
N
GLN
163
62.349
68.245
33.197
1.00
33.11

1DLC
920


ATOM
797
CA
GLN
163
61.382
68.351
34.283
1.00
34.19

1DLC
921


ATOM
798
C
GLN
163
60.081
68.977
33.769
1.00
34.41

1DLC
922


ATOM
799
O
GLN
163
58.986
68.508
34.072
1.00
35.10

1DLC
923


ATOM
800
CB
GLN
163
61.924
69.248
35.385
1.00
31.93

1DLC
924


ATOM
801
CG
GLN
163
63.188
68.789
36.034
1.00
31.11

1DLC
925


ATOM
802
CD
GLN
163
63.564
69.707
37.178
1.00
37.44

1DLC
926


ATOM
803
OE1
GLN
163
63.862
69.258
38.281
1.00
39.60

1DLC
927


ATOM
804
NE2
GLN
163
63.508
71.009
36.932
1.00
39.57

1DLC
928


ATOM
805
N
GLY
164
60.216
70.052
33.001
1.00
33.81

1DLC
929


ATOM
806
CA
GLY
164
59.058
70.733
32.446
1.00
35.60

1DLC
930


ATOM
807
C
GLY
164
58.297
69.918
31.416
1.00
35.04

1DLC
931


ATOM
808
O
GLY
164
57.116
70.156
31.188
1.00
36.07

1DLC
932


ATOM
809
N
ARG
165
58.985
68.971
30.785
1.00
36.94

1DLC
933


ATOM
810
CA
ARG
165
58.392
68.094
29.774
1.00
38.83

1DLC
934


ATOM
811
C
ARG
165
57.436
67.133
30.467
1.00
38.42

1DLC
935


ATOM
812
O
ARG
165
56.289
66.960
30.043
1.00
41.35

1DLC
936


ATOM
813
CB
ARG
165
59.496
67.291
29.061
1.00
43.60

1DLC
937


ATOM
814
CG
ARG
165
59.010
66.120
28.187
1.00
49.27

1DLC
938


ATOM
815
CD
ARG
165
60.160
65.155
27.855
1.00
55.07

1DLC
939


ATOM
816
NE
ARG
165
59.759
64.045
28.979
1.00
59.97

1DLC
940


ATOM
817
CZ
ARG
165
60.243
62.804
27.059
1.00
64.96

1DLC
941


ATOM
818
NH1
ARG
165
61.153
62.491
27.981
1.00
64.66

1DLC
942


ATOM
819
NH2
ARG
165
59.843
61.869
26.199
1.00
64.23

1DLC
943


ATOM
820
N
TLE
166
57.915
66.523
31.548
1.00
35.09

1DLC
944


ATOM
821
CA
ILE
166
57.118
65.572
32.310
1.00
33.64

1DLC
945


ATOM
822
C
ILE
166
55.992
66.289
33.081
1.00
33.53

1DLC
946


ATOM
823
O
ILE
166
54.861
65.806
33.128
1.00
31.99

1DLC
947


ATOM
824
CB
ILE
166
58.024
64.698
33.236
1.00
30.93

1DLC
948


ATOM
825
CG1
ILE
166
57.315
63.392
33.595
1.00
30.98

1DLC
949


ATOM
826
CG2
ILE
166
58.432
65.459
34.481
1.00
24.94

1DLC
950


ATOM
827
CD1
ILE
166
58.200
62.399
34.321
1.00
34.42

1DLC
951


ATOM
828
N
ARG
167
56.292
67.473
33.611
1.00
34.45

1DLC
952


ATOM
829
CA
ARG
167
55.308
68.267
34.342
1.00
32.89

1DLC
953


ATOM
830
C
ARG
167
54.109
68.617
33.476
1.00
34.17

1DLC
954


ATOM
831
O
ARG
167
52.969
68.487
33.917
1.00
35.50

1DLC
955


ATOM
832
CB
ARG
167
55.918
69.559
34.891
1.00
31.58

1DLC
956


ATOM
833
CG
ARG
167
56.805
69.377
36.112
1.00
32.53

1DLC
957


ATOM
834
CD
ARG
167
56.993
70.697
36.848
1.00
33.11

1DLC
958


ATOM
835
NE
ARG
167
57.385
71.778
35.944
1.00
37.56

1DLC
959


ATOM
836
CZ
ARG
167
58.639
72.165
35.720
1.00
35.70

1DLC
960


ATOM
837
NH1
ARG
167
59.647
71.567
36.335
1.00
35.92

1DLC
961


ATOM
836
NH2
ARG
167
58.883
73.154
34.873
1.00
36.61

1DLC
962


ATOM
839
N
GLU
168
54.346
69.050
32.242
1.00
34.64

1DLC
563


ATOM
840
CA
GLU
168
53.213
69.388
31.390
1.00
38.41

1DLC
964


ATOM
841
C
GLU
168
52.484
68.185
30.790
1.00
37.42

1DLC
965


ATOM
842
O
GLU
168
51.286
68.266
30.497
1.00
37.11

1DLC
966


ATOM
843
CB
GLU
168
53.550
70.461
30.348
1.00
41.15

1DLC
967


ATOM
844
CG
GLU
168
54.653
70.159
29.376
1.00
47.25

1DLC
968


ATOM
845
CD
GLU
168
55.073
71.413
28.623
1.00
50.54

1DLC
969


ATOM
846
0E1
GLU
168
55.649
72.322
29.266
1.00
51.72

1DLC
970


ATOM
847
0E2
GLU
168
54.808
71.504
27.402
1.00
49.76

1DLC
971


ATOM
848
N
LEU
169
53.187
67.065
30.639
1.00
35.43

1DLC
972


ATOM
849
CA
LEU
169
52.553
65.849
30.137
1.00
33.88

1DLC
973


ATOM
850
C
LEU
169
51.561
65.365
31.216
1.00
35.40

1DLC
974


ATOM
851
O
LEU
169
50.422
64.987
30.921
1.00
33.65

1DLC
975


ATOM
852
CB
LEU
169
53.593
64.752
29.876
1.00
34.42

1DLC
976


ATOM
853
CO
LEU
169
54.409
64.833
28.582
1.00
32.40

1DLC
977


ATOM
854
CD1
LEU
169
55.219
63.568
28.399
1.00
29.86

1DLC
978


ATOM
855
CD2
LEU
169
53.477
65.002
27.412
1.00
30.50

1DLC
979


ATOM
856
N
PHE
170
52.003
65.476
32.470
1.00
34.05

1DLC
980


ATOM
857
CA
PHE
170
51.193
65.107
33.625
1.00
31.26

1DLC
981


ATOM
858
C
PHE
170
49.989
66.045
33.765
1.00
31.02

1DLC
982


ATOM
859
O
PHE
170
48.861
65.584
33.685
1.00
32.68

1DLC
983


ATOM
860
CH
PHE
170
52.038
65.150
34.901
1.00
28.00

1DLC
984


ATOM
861
CG
THE
170
51.268
64.746
36.135
1.00
27.48

1DLC
985


ATOM
862
CD1
PRE
170
51.194
63.407
36.499
1.00
26.84

1DLC
986


ATOM
863
CD2
PHE
170
50.657
65.698
36.923
1.00
24.94

1DLC
987


ATOM
864
CE1
PHE
170
50.479
63.021
37.630
1.00
24.21

1DLC
988


ATOM
865
CE2
PHE
170
49.941
65.320
38.052
1.00
26.51

1DLC
989


ATOM
866
CZ
THE
170
49.852
63.977
38.405
1.00
24.66

1DLC
990


ATOM
867
N
SER
171
50.231
67.356
33.759
1.00
31.26

1DLC
991


ATOM
868
CA
SER
171
49.147
68.335
33.867
1.00
30.61

1DLC
992


ATOM
869
C
SER
171
48.107
68.152
32.770
1.00
32.20

1DLC
993


ATOM
870
O
SER
171
46.915
68.359
32.996
1.00
32.31

1DLC
994


ATOM
871
CB
SER
171
49.681
69.766
33.821
1.00
30.26

1DLC
995


ATOM
872
00
SHR
171
50.166
70.179
35.089
1.00
36.66

1DLC
995


ATOM
873
N
GLN
172
48.563
67.781
31.577
1.00
31.91

1DLC
997


ATOM
874
CA
GLN
172
47.659
67.552
30.455
1.00
33.14

1DLC
998


ATOM
875
C
GLN
172
46.733
66.365
30.710
1.00
29.58

1DLC
999


ATOM
876
O
GLN
172
45.516
66.488
30.614
1.00
30.17

1DLC
1000


ATOM
877
CB
GLN
172
48.445
67.330
29.155
1.00
37.12

1DLC
1001


ATOM
878
CG
GLN
172
48.917
68.614
28.486
1.00
45.43

1DLC
1002


ATOM
879
CD
GLN
172
47.759
69.492
28.022
1.00
49.43

1DLC
1003


ATOM
880
OE1
GLN
172
46.967
69.099
27.163
1.00
52.00

1DLC
1004


ATOM
881
NE2
GLN
172
47.660
70.688
28.586
1.00
49.43

1DLC
1005


ATOM
882
N
ALA
173
47.313
65.223
31.057
1.00
24.78

1DLC
1006


ATOM
883
CA
ALA
173
46.533
64.027
31.321
1.00
22.98

1DLC
1007


ATOM
884
C
ALA
173
45.524
64.270
32.442
1.00
24.72

1DLC
1008


ATOM
885
O
ALA
173
44.319
64.077
32.254
1.00
28.98

1DLC
1009


ATOM
886
CB
ALA
173
47.448
62.864
31.662
1.00
17.04

1DLC
1010


ATOM
887
N
GLU
174
46.007
64.756
33.583
1.00
22.65

1DLC
1011


ATOM
888
CA
GLU
174
45.153
65.032
34.739
1.00
22.62

1DLC
1012


ATOM
869
C
GLU
174
43.983
65.962
34.379
1.00
23.92

1DLC
1013


ATOM
890
O
GLU
174
42.821
65.690
34.703
1.00
24.12

1DLC
1014


ATOM
891
CB
GLU
174
45.993
65.646
35.862
1.00
20.71

1DLC
1015


ATOM
892
CG
GLU
174
45.347
65.635
37.245
1.00
27.17

1DLC
1016


ATOM
893
CD
GLU
174
44.233
66.665
37.422
1.00
26.70

1DLC
1017


ATOM
894
OE1
GLU
174
44.464
67.856
37.132
1.00
30.91

1DLC
1018


ATOM
895
OE2
GLU
174
43.129
66.287
37.864
1.00
25.52

1DLC
1019


ATOM
896
N
SER
175
44.301
67.045
33.684
1.00
25.54

1DLC
1020


ATOM
897
CA
SER
175
43.308
68.022
33.262
1.00
25.56

1DLC
1021


ATOM
898
C
SER
175
42.301
67.409
32.283
1.00
27.17

1DLC
1022


ATOM
899
O
SER
175
41.097
67.641
32.389
1.00
27.41

1DLC
1023


ATOM
900
CB
SER
175
44.006
69.214
32.611
1.00
23.74

1DLC
1024


ATOM
901
OG 
SEP
175
43.135
70.322
32.527
1.00
33.11

1DLC
1025


ATOM
902
N
HIS
176
42.941
66.593
31.354
1.00
29.90

1DLC
1026


ATOM
903
CA
HIS
176
41.941
65.937
30.354
1.00
30.36

1DLC
1027


ATOM
904
C
HIS
176
40.948
65.023
31.080
1.00
28.97

1DLC
1028


ATOM
905
O
HIS
176
39.793
64.905
30.675
1.00
29.85

1DLC
1029


ATOM
906
CB
HIS
176
42.795
65.139
29.367
1.00
34.90

1DLC
1030


ATOM
907
CG
HIS
176
42.059
64.703
28.131
1.00
46.08

1DLC
1031


ATOM
908
ND1
HIS
176
40.692
64.506
28.094
1.00
49.82

1DLC
1032


ATOM
909
CD2
HIS
176
42.510
54.405
26.888
1.00
48.94

1DLC
1033


ATOM
910
CE1
HIS
176
40.335
64.107
26.686
1.00
50.00

1DLC
1034


ATOM
911
NE2
HIS
176
41.421
64.036
26.135
1.00
50.95

1DLC
1035


ATOM
912
N
PHE
177
41.386
64.401
32.165
1.00
26.81

1DLC
1036


ATOM
913
CA
PHE
177
40.501
63.525
32.916
1.00
27.11

1DLC
1037


ATOM
914
C
PHE
177
39.326
64.261
33.562
1.00
25.34

1DLC
1038


ATOM
915
O
PHE
177
38.188
63.814
33.482
1.00
26.87

1DLC
1039


ATOM
916
CB
PHE
177
41.285
62.731
33.961
1.00
27.16

1DLC
1040


ATOM
917
CG
PHE
177
41.851
61.443
13.439
1.00
27.15

1DLC
1041


ATOM
918
CD1
PHE
177
41.033
60.321
33.292
1.00
26.85

1DLC
1042


ATOM
919
CD2
PHE
177
43.188
61.352
33.074
1.00
24.38

1DLC
1043


ATOM
920
CE1
PRE
177
41.544
59.127
32.787
1.00
26.71

1DLC
1044


ATOM
921
CE2
PRE
177
43.706
60.172
32.571
1.00
26.25

1DLC
1045


ATOM
922
CZ 
PHE
177
42.882
59.055
32.426
1.00
27.48

1DLC
1046


ATOM
923
N
ARG
178
39.595
65.400
34.163
1.00
24.09

1DLC
1047


ATOM
924
CA
ARO
178
38.534
66.168
34.821
1.00
21.65

1DLC
1048


ATOM
925
C
ARG
178
37.544
66.715
33.796
1.00
25.36

1DLC
1049


ATOM
926
O
ARG
178
36.344
66.828
34.049
1.00
28.72

1DLC
1050


ATOM
927
CB
ARG
178
39.128
67.309
35.637
1.00
18.36

1DLC
1051


ATOM
928
CG
ARG
178
39.744
66.866
36.940
1.00
19.50

1DLC
1052


ATOM
929
CD
ARO
178
40.263
68.050
37.730
1.00
18.54

1DLC
1053


ATOM
930
NE
ARG
178
41.446
68.641
37.119
1.00
19.88

1DLC
1054


ATOM
931
CZ
ARG
178
41.544
69.911
36.742
1.00
23.68

1DLC
1055


ATOM
932
NH1
ARG
178
40.522
70.739
36.906
1.00
25.01

1DLC
1056


ATOM
933
NH2
ARG
178
42.669
70.356
36.202
1.00
22.04

1DLC
1057


ATOM
934
N
ASN
179
38.056
67.009
32.614
1.00
26.63

1DLC
1058


ATOM
935
CA
ASN
179
37.241
67.544
31.548
1.00
30.38

1DLC
1059


ATOM
936
C
ASN
179
36.323
66.476
30.938
1.00
32.76

1DLC
1060


ATOM
937
O
ASN
179
35.156
66.742
30.636
1.00
33.01

1DLC
1061


ATOM
938
CB
ASN 
179
38.163
68.128
30.487
1.00
38.68

1DLC
1062


ATOM
939
CG
ASN 
179
37.478
69.159
29.638
1.00
50.42

1DLC
1063


ATOM
940
OD1
ASN
179
37.101
68.889
28.496
1.00
58.00

1DLC
1064


ATOM
941
ND2
ASN
179
37.295
70.353
30.191
1.00
56.89

1DLC
1065


ATOM
942
N
SER 
180
36.849
65.257
30.815
1.00
31.80

1DLC
1066


ATOM
943
CA
SER 
180
36.123
64.128
30.229
1.00
29.25

1DLC
1067


ATOM
944
C
SER 
180
35.138
63.345
31.101
1.00
28.52

1DLC
1068


ATOM
945
O
SER 
180
34.139
62.844
30.592
1.00
29.31

1DLC
1069


ATOM
946
CB
SER
180
37.108
63.140
29.606
1.00
26.37

1DLC
1070


ATOM
947
OG
SER
180
37.889
63.706
28.624
1.00
28.28

1DLC
1071


ATOM
948
N
MET
181
35.411
63.222
32.397
1.00
25.80

1D1C
1072


ATOM
949
CA
MET
181
34.535
62.467
33.295
1.00
24.36

1DLC
1073


ATOM
950
C
MET
181
33.013
62.660
33.109
1.00
25.40

1DLC
1074


ATOM
951
O
MET
181
32.260
61.678
33.070
1.00
25.51

1DLC
1075


ATOM
952
CB
MET
181
34.939
62.674
34.760
1.00
19.33

1DLC
1076


ATOM
953
CO 
MET
181
36.253
61.994
35.152
1.00
20.86

1DLC
1077


ATOM
954
SD
MET
181
36.411
60.263
34.634
1.00
21.66

1DLC
1078


ATOM
955
CE
MET
181
35.276
59.487
35.735
1.00
16.01

1DLC
1079


ATOM
956
N
PRO
182
32.545
63.913
32.954
1.00
25.51

1DLC
1080


ATOM
957
CA
PRO 
182
31.103
64.138
32.772
1.00
25.99

1DLC
1081


ATOM
958
C
PRO 
182
30.491
63.331
31.615
1.00
25.29

1DLC
1082


ATOM
959
O
PRO
182
29.311
63.003
31.640
1.00
27.08

1DLC
1083


ATOM
960
CB
PRO
182
31.031
65.640
32.507
1.00
25.60

1DLC
1084


ATOM
961
CG
PRO
182
32.160
66.174
33.318
1.00
23.18

1DLC
1085


ATOM
962
CD
PRO 
182
33.264
65.200
33.011
1.00
25.77

1DLC
1086


ATOM
963
N
SER
183
31.303
63.000
30.617
1.00
24.96

1DLC
1087


ATOM
964
CA
SER 
183
30.842
62.226
29.465
1.00
26.52

1DLC
1088


ATOM
965
C
SER 
183
30.491
60.792
29.817
1.00
26.32

1DLC
1089


ATOM
966
O
SER
183
29.785
60.122
29.068
1.00
29.73

1DLC
1090


ATOM
967
CB
SER
183
31.899
62.204
28.356
1.00
25.87

1DLC
1091


ATOM
968
OG 
SER 
183
31.952
63.438
27.666
1.00
34.94

1DLC
1092


ATOM
969
N
PHE
184
31.025
60.300
30.928
1.00
26.09

1DLC
1093


ATOM
970
CA
PHE
184
30.754
58.928
31.357
1.00
25.51

1DLC
1094


ATOM
971
C
PHE
184
29.683
58.923
32.447
1.00
24.26

1DLC
1095


ATOM
972
O
PHE
184
29.529
57.957
33.188
1.00
24.61

1DLC
1096


ATOM
973
CB
PHE
184
32.039
58.266
31.859
1.00
23.91

1DLC
1097


ATOM
974
CG
PHE
184
33.248
58.594
31.031
1.00
25.50

1DLC
1098


ATOM
975
CD1
PHE
184
33.228
58.437
29.648
1.00
25.62

1DLC
1099


ATOM
976
CD2
PHE
184
34.402
59.085
31.630
1.00
23.80

1DLC
1100


ATOM
977
CE1
PHE 
184
34.339
58.767
28.876
1.00
26.43

1DLC
1101


ATOM
978
CE2
PHE 
184
35.515
59.418
30.866
1.00
24.57

1DLC
1102


ATOM
979
CZ 
PHE
184
35.485
59.260
29.488
1.00
23.14

1DLC
1101


ATOM
980
N
ALA
165
28.925
60.007
32.522
1.00
23.06

1DLC
1104


ATOM
981
CA
ALA
185
27.879
60.119
33.518
1.00
24.13

1DLC
1105


ATOM
982
C
ALA
185
26.708
60.976
33.041
1.00
23.68

1DLC
1106


ATOM
983
O
ALA
185
26.076
61.650
33.841
1.00
27.10

1DLC
1107


ATOM
984
CB
ALA
185
28.461
60.691
34.803
1.00
19.53

1DLC
1108


ATOM
985
N
ILE
186
26.396
60.930
31.749
1.00
26.51

1DLC
1109


ATOM
986
CA
ILE
186
25.287
61.737
31.219
1.00
30.55

1DLC
1110


ATOM
987
C
ILE 
186
23.923
61.273
31.738
1.00
31.15

1DLC
1111


ATOM
988
O
ILE
186
23.660
60.073
31.881
1.00
30.54

1DLC
1112


ATOM
989
CB
ILE 
186
25.310
61.876
29.645
1.00
32.49

1DLC
1113


ATOM
990
CG1
ILE
186
23.994
61.413
29.014
1.00
35.37

1DLC
1114


ATOM
991
CG2
ILE 
186
26.506
61.164
29.036
1.00
32.13

1DLC
1115


ATOM
992
CD1
ILE
186
22.958
62.522
28.851
1.00
41.70

1DLC
1116


ATOM
993
N
SEE
167
23.061
62.243
32.025
1.00
34.59

1DLC
1117


ATOM
994
CA
SER
187
21.730
61.969
32.570
1.00
35.55

1DLC
1118


ATOM
995
C
SER
187
20.948
60.887
31.836
1.00
32.95

1DLC
1119


ATOM
996
O
SER
187
20.761
60.942
30.620
1.00
33.44

1DLC
1120


ATOM
997
CB
SER
187
20.905
63.252
32.665
1.00
35.13

1DLC
1121


ATOM
998
OG
SER
187
10.848
63.077
33.595
1.00
42.12

1DLC
1122


ATOM
999
N
GLY
188
20.493
59.899
32.593
1.00
30.43

1DLC
1123


ATOM
1000
CA
GLY
188
19.761
58.799
32.001
1.00
28.56

1DLC
1124


ATOM
1001
C
GLY
188
20.642
57.624
31.609
1.00
28.57

1DLC
1125


ATOM
1002
O
GLY
188
20.135
56.536
31.335
1.00
31.17

1DLC
1126


ATOM
1003
N
TYR
189
21.957
57.821
31.584
1.00
27.24

1DLC
1127


ATOM
1004
CA
TYR
189
22.870
56.734
31.222
1.00
27.78

1DLC
1128


ATOM
1005
C
TYR
189
23.913
56.391
32.282
1.00
25.94

1DLC
1129


ATOM
1006
O
TYR
189
24.832
55.615
32.031
1.00
27.94

1DLC
1130


ATOM
1007
CB
TYR 
189
23.541
57.031
29.883
1.00
30.52

1DLC
1131


ATOM
1008
CG
TYR
189
22.541
57.088
28.765
1.00
35.63

1DLC
1132


ATOM
1009
CD1
TYR
189
21.957
55.925
28.280
1.00
37.70

1DLC
1133


ATOM
1010
CD2
TYR
189
22.125
58.307
28.237
1.00
38.49

1DLC
1134


ATOM
1011
CE1
TYR
189
20.979
55.967
27.302
1.00
44.20

1DLC
1135


ATOM
1012
CE2
TYR 
189
21.146
58.366
27.255
1.00
43.26

1DLC
1136


ATOM
1013
CZ
TYR
189
20.573
57.190
26.791
1.00
47.00

1DLC
1137


ATOM
1014
OH
TYR
189
19.593
57.227
25.816
1.00
53.52

1DLC
1138


ATOM
1015
N
GLU
190
23.719
56.921
33.484
1.00
24.53

1DLC
1139


ATOM
1016
CA
GLU
190
24.624
56.700
34.609
1.00
23.53

1DLC
1140


ATOM
1017
C
GLU 
190
24.978
55.243
34.900
1.00
24.17

1DLC
1141


ATOM
1018
O
GLU 
190
26.153
54.912
35.031
1.00
27.99

1DLC
1142


ATOM
1019
CR 
GLU
190
24.068
57.352
35.872
1.00
24.72

1DLC
1143


ATOM
1020
CO
GLU 
190
23.907
58.865
35.776
1.00
26.76

1DLC
1144


ATOM
1021
CD
GLU 
190
22.541
59.318
35.278
1.00
25.80

1DLC
1145


ATOM
1022
CE1
GLU
190
21.778
58.510
14.738
1.00
26.88

1DLC
1146


ATOM
1023
CE2
GLU
190
22.219
60.502
35.471
1.00
30.62

1DLC
1147


ATOM
1024
N
VAL
191
23.973
54.375
34.996
1.00
23.30

1DLC
1148


ATOM
1025
CA
VAL
191
24.207
52.952
35.272
1.00
19.79

1DLC
1149


ATOM
1026
C
VAL
191
24.897
52.243
34.108
1.00
19.46

1DLC
1150


ATOM
1027
O
VAL
191
25.799
51.432
34.308
1.00
22.56

1DLC
1151


ATOM
1028
CB
VAL 
191
22.889
52.203
35.615
1.00
18.04

1DLC
1152


ATOM
1029
CG1
VAL
191
23.163
50.719
35.865
1.00
18.90

1DLC
1153


ATOM
1030
CG2
VAL
191
22.232
52.824
36.045
1.00
20.32

1DLC
1154


ATOM
1031
N
LEU 
192
24.491
52.566
32.890
1.00
18.69

1DLC
1155


ATOM
1032
CA
LEU
192
25.082
51.941
31.717
1.00
19.74

1DLC
1156


ATOM
1033
C
LEU
192
26.572
52.295
31.545
1.00
20.71

1DLC
1157


ATOM
1034
O
LEU
192
27.359
51.487
31.061
1.00
21.17

1DLC
1158


ATOM
1035
CB
LEU 
192
24.271
52.294
30.464
1.00
18.07

1DLC
1159


ATOM
1036
CO
LEU
192
22.806
51.827
30.419
1.00
20.22

1DLC
1160


ATOM
1037
CD1
LEU
192
22.152
52.272
29.115
1.00
18.09

1DLC
1161


ATOM
1038
CD2
LEU
192
22.717
50.312
30.547
1.00
20.02

1DLC
1162


ATOM
1039
N
PHE
193
26.955
53.496
31.962
1.00
20.56

1DLC
1163


ATOM
1040
CA
PHE
193
28.348
53.942
31.871
1.00
20.78

1DLC
1164


ATOM
1041
C
PHE
193
29.168
53.568
33.104
1.00
21.28

1DLC
1165


ATOM
1042
O
PHE
193
30.340
53.907
33.174
1.00
23.88

1DLC
1166


ATOM
1043
CB
PHE
193
28.402
55.470
31.765
1.00
20.19

1DLC
1167


ATOM
1044
CG
PHE
193
28.185
56.011
30.386
1.00
23.31

1DLC
1168


ATOM
1045
CD1
PHE
193
29.016
55.646
29.333
1.00
20.93

1DLC
1169


ATOM
1046
CD2
PHE
193
27.178
56.943
30.151
1.00
23.78

1DLC
1170


ATOM
1047
CE1
PRE
193
28.848
56.205
28.066
1.00
23.90

1DLC
1171


ATOM
1048
CE2
PHE
193
27.005
57.506
28.886
1.00
25.20

1DLC
1172


ATOM
1049
CE
PHE
193
27.842
57.137
27.845
1.00
20.39

1DLC
1173


ATOM
1050
N
LEU 
194
28.566
52.872
34.065
1.00
22.74

1DLC
1174


ATOM
1051
CA
LEU 
194
29.242
52.536
35.324
1.00
21.21

1DLC
1175


ATOM
1052
C
LEU
194
30.634
51.887
35.302
1.00
21.36

1DLC
1176


ATOM
1053
O
LEU
194
31.533
52.328
36.019
1.00
20.76

1DLC
1177


ATOM
1054
CB
LEU 
194
28.297
51.768
36.263
1.00
17.75

1DLC
1172


ATOM
1055
CG
LEU
194
28.574
51.952
37.766
1.00
16.29

1DLC
1179


ATOM
1056
CD1
LEU
194
28.602
53.452
38.103
1.00
11.60

1DLC
1180


ATOM
1057
CD2
LEU
194
27.528
51.257
38.608
1.00
12.55

1DLC
1181


ATOM
1058
N
THR
195
30.525
50.841
34.507
1.00
22.96

1DLC
1182


ATOM
1059
CA
THR
195
32.140
50.197
34.451
1.00
22.99

1DLC
1183


ATOM
1060
C
THR
195
33.160
51.083
33.716
1.00
22.92

1DLC
1184


ATOM
1061
O
THR
195
34.343
51.108
34.061
1.00
24.03

1DLC
1185


ATOM
1062
CB
THR
195
32.067
48.777
33.832
1.00
22.11

1DLC
1186


ATOM
1063
CG1
THR
195
21.554
45.555
32.498
1.00
27.92

1DLC
1187


ATOM
1064
CG2
THR
195
31.150
47.896
34.663
1.00
19.33

1DLC
1188


ATOM
1065
N
THR
196
32.681
51.845
32.738
1.00
19.98

1DLC
1189


ATOM
1066
CA
THR
196
33.521
52.768
31.987
1.00
19.69

1DLC
1190


ATOM
1067
C
THR
196
33.958
53.893
32.925
1.00
20.38

1DLC
1191


ATOM
1068
O
THR
196
35.132
54.233
32.983
1.00
25.74

1DLC
1192


ATOM
1069
CB
THR
196
32.748
53.374
30.805
1.00
21.39

1DLC
1193


ATOM
1070
CG1
THR
196
32.366
52.330
29.903
1.00
23.90

1DLC
1194


ATOM
1071
CG2
THR
196
33.598
54.387
30.064
1.00
22.13

1DLC
1195


ATOM
1072
N
TYR
197
33.011
54.457
33.671
1.00
20.18

1DLC
1196


ATOM
1073
CA
TYR
197
33.292
55.529
34.630
1.00
19.63

1DLC
1197


ATOM
1074
C
TYR
197
34.236
55.009
35.717
1.00
21.21

1DLC
1198


ATOM
1075
O
TYR
197
35.208
55.668
36.072
1.00
23.03

1DLC
1199


ATOM
1076
CB
TYR
197
31.986
56.019
35.271
1.00
18.30

1DLC
1200


ATOM
1077
CG
TYR
197
32.119
57.108
36.326
1.00
14.96

1DLC
1201


ATOM
1078
CD1
TYR
197
32.471
56.799
37.639
1.00
16.47

1DLC
1202


ATOM
1079
CD2
TYR
197
31.840
58.443
36.020
1.00
16.19

1DLC
1203


ATOM
1080
CE1
TYR
197
32.540
57.784
38.620
1.00
16.31

1DLC
1204


ATOM
1081
CE2
TYR
197
31.903
59.442
36.995
1.00
14.65

1DLC
1205


ATOM
1082
CZ
TYR
197
32.252
59.103
38.296
1.00
18.45

1DLC
1206


ATOM
1083
OH
TYR
197
32.292
60.067
39.287
1.00
22.05

1DLC
1207


ATOM
1084
N
ALA
198
33.961
53.815
36.229
1.00
21.60

1DLC
1208


ATOM
1085
CA
ALA
198
34.793
53.225
37.277
1.00
21.41

1DLC
1209


ATOM
1086
C
ALA
198
36.259
53.101
36.852
1.00
20.73

1DLC
1210


ATOM
1087
O
ALA
198
37.157
53.523
37.579
1.00
19.18

1DLC
1211


ATOM
1088
CB
ALA
198
34.239
51.867
37.687
1.00
21.88

1DLC
1212


ATOM
1089
N
GLN
199
36.478
52.560
35.654
1.00
19.43

1DLC
1213


ATOM
1090
CA
GLN
199
37.816
52.374
35.100
1.00
19.21

1DLC
1214


ATOM
1091
C
GLN
199
38.515
53.708
34.780
1.00
21.06

1DLC
1215


ATOM
1092
O
GLN
199
39.726
53.849
34.969
1.00
22.54

1DLC
1216


ATOM
1093
CB
GLN
199
37.747
51.488
33.855
1.00
19.94

1DLC
1217


ATOM
1094
CG
GLN
199
37.211
50.082
34.106
1.00
21.16

1DLC
1218


ATOM
1095
CD
GLN
199
38.146
49.221
34.949
1.00
26.14

1DLC
1219


ATOM
1096
OE1
GLN
199
39.348
49.465
35.003
1.00
28.88

1DLC
1220


ATOM
1097
NE2
GLN
199
37.594
48.201
35.605
1.00
26.51

1DLC
1221


ATOM
1098
N
ALA
200
37.755
54.690
34.309
1.00
18.59

1DLC
1222


ATOM
1099
CA
ALA
200
38.318
56.002
34.006
1.00
17.37

1DLC
1223


ATOM
1100
C
ALA
200
36.668
56.712
35.316
1.00
19.35

1DLC
1224


ATOM
1101
O
ALA
200
39.754
57.287
35.455
1.00
22.44

1DLC
1225


ATOM
1102
CB
ALA
200
37.331
56.827
33.203
1.00
12.83

1DLC
1226


ATOM
1103
N
ALA
201
37.762
56.625
36.291
1.00
21.10

1DLC
1227


ATOM
1104
CA
ALA
201
37.946
57.232
37.612
1.00
18.23

1DLC
1228


ATOM
1105
C
ALA
201
39.206
56.667
38.259
1.00
18.71

1DLC
1229


ATOM
1106
O
ALA
201
40.045
57.404
38.769
1.00
22.55

1DLC
1230


ATOM
1107
CB
ALA
201
36.737
56.948
38.497
1.00
14.73

1DLC
1231


ATOM
1108
N
ASN
202
39.342
55.349
38.211
1.00
18.93

1DLC
1232


ATOM
1109
CA
ASN
202
40.506
54.674
38.773
1.00
19.98

1DLC
1233


ATOM
1110
C
ASN
202
41.795
55.231
38.172
1.00
20.62

1DLC
1234


ATOM
1111
O
ASN
202
42.723
55.601
38.897
1.00
20.33

1DLC
1235


ATOM
1112
CB
ASN
202
40.418
53.172
38.501
1.00
19.83

1DLC
1236


ATOM
1113
CG
ASN
202
41.612
52.418
39.032
1.00
19.77

1DLC
1237


ATOM
1114
OD1
ASN
202
42.334
51.761
38.278
1.00
23.18

1DLC
1238


ATOM
1115
ND2
ASN
202
41.835
52.509
40.332
1.00
14.55

1DLC
1239


ATOM
1116
N
THR
203
41.842
55.287
36.844
1.00
21.70

1DLC
1240


ATOM
1117
CA
THR
203
43.007
55.805
36.138
1.00
22.47

1DLC
1241


ATOM
1118
C
THR
203
43.322
57.223
36.631
1.00
23.03

1DLC
1242


ATOM
1119
O
THR
203
44.428
57.496
37.091
1.00
24.63

1DLC
1243


ATOM
1120
CB
THR
203
42.789
55.827
34.593
1.00
24.20

1DLC
1244


ATOM
1121
OG1
THR
203
42.470
54.507
34.123
1.00
17.39

1DLC
1245


ATOM
1122
CG2
THR
203
44.058
56.319
33.877
1.00
22.82

1DLC
1246


ATOM
1123
N
HIS
204
42.318
58.091
36.619
1.00
20.16

1DLC
1247


ATOM
1124
CA
HIS
204
42.485
59.468
37.064
1.00
18.30

1DLC
1248


ATOM
1125
C
HIS
204
43.123
59.566
38.451
1.00
19.42

1DLC
1249


ATOM
1126
O
HIS
204
44.064
60.328
38.651
1.00
23.12

1DLC
1250


ATOM
1127
CB
HIS
204
41.131
60.190
37.066
1.00
15.98

1DLC
1251


ATOM
1128
CO
HIS
204
41.224
61.664
37.314
1.00
15.26

1DLC
1252


ATOM
1129
ND1
HIS
204
40.123
62.443
37.582
1.00
18.22

1DLC
1253


ATOM
1130
CD2
HIS
204
42.285
62.508
37.302
1.00
14.66

1DLC
1254


ATOM
1131
CE1
HIS
204
40.495
63.703
37.719
1.00
17.73

1DLC
1255


ATOM
1132
NE2
HIS
204
41.803
63.768
37.554
1.00
15.61

1DLC
1256


ATOM
1133
N
LEU
205
42.603
58.810
39.410
1.00
19.20

1DLC
1257


ATOM
1134
CA
LEU
205
43.131
58.845
40.772
1.00
19.71

1DLC
1258


ATOM
1135
C
LEU
205
44.519
58.227
40.904
1.00
21.25

1DLC
1259


ATOM
1136
O
LEU
205
45.356
58.725
41.666
1.00
21.63

1DLC
1260


ATOM
1137
CB
LEU
205
42.168
58.161
41.745
1.00
18.84

1DLC
1261


ATOM
1138
CG
LEU
205
40.886
58.921
42.052
1.00
18.00

1DLC
1262


ATOM
1139
CD1
LEU
205
40.010
58.052
42.908
1.00
20.41

1DLC
1263


ATOM
1140
CD2
LEU
205
41.197
60.226
42.759
1.00
18.32

1DLC
1264


ATOM
1141
N
PHE
206
44.761
57.137
40.177
1.00
20.18

1DLC
1265


ATOM
1142
CA
PHE
206
46.060
56.477
40.233
1.00
20.34

1DLC
1266


ATOM
1143
C
PHE
206
47.117
57.423
39.677
1.00
20.04

1DLC
1267


ATOM
1144
O
PHE
206
45.221
57.522
40.192
1.00
21.09

1DLC
1268


ATOM
1145
CB
PHE
206
46.051
55.175
39.438
1.00
18.45

1DLC
1269


ATOM
1146
CG
PHE
206
47.169
54.263
39.798
1.00
16.28

1DLC
1270


ATOM
1147
CD1
PHE
206
47.221
53.683
41.063
1.00
14.90

1DLC
1271


ATOM
1148
CD2
PHE
206
46.196
54.006
38.897
1.00
16.65

1DLC
1272


ATOM
1149
CE1
PHE
206
48.279
52.863
41.423
1.00
15.74

1DLC
1273


ATOM
1150
CE2
PHE
206
49.259
53.185
39.247
1.00
14.95

1DLC
1274


ATOM
1151
CZ
PHE
206
49.303
52.612
40.510
1.00
13.30

1DLC
1275


ATOM
1152
N
LEU
207
46.737
58.124
38.621
1.00
21.24

1DLC
1276


ATOM
1153
CA
LEU
207
47.575
59.112
37.955
1.00
22.23

1DLC
1277


ATOM
1154
C
LET
207
47.927
60.224
38.966
1.00
23.44

1DLC
1278


ATOM
1155
O
LEU
207
49.098
60.547
39.190
1.00
22.70

1DLC
1279


ATOM
1156
CB
LEU
207
46.758
59.698
36.801
1.00
23.02

1DLC
1280


ATOM
1157
CG
LEU
207
47.360
60.368
35.571
1.00
31.73

1DLC
1281


ATOM
1158
CD1
LEU
207
47.968
61.698
35.942
1.00
33.70

1DLC
1282


ATOM
1159
CD2
LEU
207
48.369
59.439
34.915
1.00
34.96

1DLC
1283


ATOM
1160
N
LEU
208
46.894
60.762
39.610
1.00
22.59

1DLC
1284


ATOM
1161
CA
LEU
208
47.044
61.837
40.584
1.00
20.00

1DLC
1285


ATOM
1162
C
LEU
208
48.056
61.607
41.704
1.00
20.94

1DLC
1286


ATOM
1163
O
LEU
208
48.819
62.514
42.046
1.00
22.20

1DLC
1257


ATOM
1164
CE
LET
208
45.686
62.194
41.188
1.00
16.43

1DLC
1288


ATOM
1165
CO
LEU
208
44.872
63.256
40.452
1.00
17.48

1DLC
1289


ATOM
1166
CD1
LEU
208
43.449
63.277
40.998
1.00
19.96

1DLC
1290


ATOM
1167
CD2
LEU
208
45.527
64.630
40.597
1.00
13.67

1DLC
1291


ATOM
1168
N
LYS
209
48.073
60.410
42.282
1.00
20.58

1DLC
1292


ATOM
1169
CA
LYS
209
48.998
60.137
43.378
1.00
20.54

1DLC
1293


ATOM
1170
C
LYS
209
50.479
60.260
42.979
1.00
23.16

1DLC
1294


ATOM
1171
O
LYS
209
51.335
60.554
43.821
1.00
23.16

1DLC
1295


ATOM
1172
CR
LYS
209
48.672
58.798
44.057
1.00
16.68

1DLC
1296


ATOM
1173
CO
LYS
209
48.825
57.563
43.202
1.00
18.68

1DLC
1297


ATOM
1174
CD
LYS
209
50.232
57.019
43.295
1.00
18.58

1DLC
1298


ATOM
1175
CE
LYS
209
50.369
55.683
42.589
1.00
21.11

1DLC
1299


ATOM
1176
NZ
LYS
209
50.185
55.764
41.111
1.00
21.88

1DLC
1300


ATOM
1177
N
ASP
210
50.763
60.130
41.684
1.00
21.08

1DLC
1301


ATOM
1178
CA
ASP
210
52.131
60.261
41.191
1.00
19.70

1DLC
1302


ATOM
1179
C
ASP
210
52.703
61.647
41.503
1.00
20.97

1DLC
1303


ATOM
1180
O
ASP
210
53.907
61.798
41.741
1.00
21.99

1DLC
1304


ATOM
1181
CB
ASP
210
52.193
59.982
39.689
1.00
19.34

1DLC
1305


ATOM
1182
CG
ASP
210
52.109
58.504
39.366
1.00
19.19

1DLC
1306


ATOM
1183
OD1
ASP
210
51.971
57.689
40.298
1.00
19.56

1DLC
1307


ATOM
1184
OD2
ASP
210
52.205
58.153
38.178
1.00
21.76

1DLC
1308


ATOM
1185
N
ALA
211
51.829
62.650
41.540
1.00
19.23

1DLC
1309


ATOM
1186
CA
ALA
211
52.241
64.015
41.858
1.00
19.70

1DLC
1310


ATOM
1187
C
ALA
211
52.795
64.116
43.287
1.00
19.61

1DLC
1311


ATOM
1188
O
ALA
211
53.601
64.990
43.583
1.00
22.55

1DLC
1312


ATOM
1189
CS 
ALA
211
51.072
64.979
41.680
1.00
15.73

1DLC
1313


ATOM
1190
N
GLN
212
52.365
63.227
44.177
1.00
18.98

1DLC
1314


ATOM
1191
CA
GLN
212
52.856
63.265
45.557
1.00
19.82

1DLC
1315


ATOM
1192
C
GLN
212
54.149
62.482
45.687
1.00
19.72

1DLC
1316


ATOM
1193
O
GLN
212
54.903
62.674
46.632
1.00
22.58

1DLC
1317


ATOM
1194
CB
GLN
212
51.819
62.718
46.556
1.00
15.61

1DLC
1318


ATOM
1195
CG
GLN
212
50.456
63.394
46.496
1.00
12.71

1DLC
1319


ATOM
1196
CD
GLN
212
50.538
64.903
46.573
1.00
12.86

1DLC
1320


ATOM
1197
OE1
GLN
212
51.103
65.454
47.503
1.00
14.37

1DLC
1321


ATOM
1198
NE2
GLN
212
49.964
65.578
45.593
1.00
10.00

1DLC
1322


ATOM
1199
N
ILE
213
54.389
61.582
44.741
1.00
22.18

1DLC
1323


ATOM
1200
CA
ILE
213
55.594
60.767
44.752
1.00
20.68

1DLC
1324


ATOM
1201
C
ILE
213
56.754
61.481
44.057
1.00
22.54

1DLC
1325


ATOM
1202
O
ILE
213
57.836
61.622
44.623
1.00
21.78

1DLC
1326


ATOM
1203
CB
ILE
213
55.356
59.419
44.054
1.00
20.69

1DLC
1327


ATOM
1204
CG
1ILE
213
54.347
58.579
44.840
1.00
17.63

1DLC
1328


ATOM
1205
CG2
ILE
213
56.670
58.666
43.909
1.00
25.19

1DLC
1329


ATOM
1206
CD1
ILE
213
54.045
57.240
44.188
1.00
12.68

1DLC
1330


ATOM
1207
N
TYR
214
56.508
61.952
42.838
1.00
23.00

1DLC
1331


ATOM
1208
CA
TYR
214
57.528
62.631
42.043
1.00
22.33

1DLC
1332


ATOM
1209
C
TYR
214
57.425
64.154
41.979
1.00
24.14

1DLC
1333


ATOM
1210
O
TYR
214
58.269
64.801
41.374
1.00
28.23

1DLC
1334


ATOM
1211
CB
TYR
214
57.488
62.100
40.615
1.00
23.32

1DLC
1335


ATOM
1212
CG
TYR
214
57.727
60.620
40.479
1.00
26.06

1DLC
1336


ATOM
1213
CD1
TYR
214
59.009
60.092
40.618
1.00
27.10

1DLC
1337


ATOM
1214
CD2
TYR
214
56.678
59.746
40.184
1.00
25.78

1DLC
1338


ATOM
1215
CE1
TYR
214
59.249
58.728
40.466
1.00
32.00

1DLC
1339


ATOM
1216
CE2
TYR
214
56.907
58.374
40.026
1.00
31.14

10LC
1340


ATOM
1217
CZ 
TYR
214
58.199
57.874
40.169
1.00
32.77

1DLC
1341


ATOM
1218
OH
TYR
214
58.452
56.529
40.017
1.00
37.11

1DLC
1342


ATOM
1219
N
GLY
215
56.398
64.724
42.596
1.00
25.34

1DLC
1343


ATOM
1220
CA
GLY
215
56.198
66.166
42.560
1.00
27.83

1DLC
1344


ATOM
1221
C
GLY
215
57.419
67.067
42.648
1.00
29.47

1DLC
1345


ATOM
1222
O
GLY
215
57.663
67.867
41.746
1.00
28.30

1DLC
1346


ATOM
1223
N
GLU
216
58.174
66.954
43.737
1.00
32.54

1DLC
1347


ATOM
1224
CA
GLU
216
59.368
67.769
43.918
1.00
36.48

1DLC
1345


ATOM
1225
C
GLU
216
60.485
67.450
42.917
1.00
35.87

1DLC
1349


ATOM
1226
O
GLU
216
61.148
68.358
42.427
1.00
36.74

1DLC
1350


ATOM
1227
CB
GLU
216
59.878
67.676
45.351
1.00
41.84

1DLC
1351


ATOM
1228
CG
GLU
216
58.947
68.318
46.371
1.00
54.52

1DLC
1352


ATOM
1229
CD
GLU
216
59.656
68.698
47.671
1.00
64.18

1DLC
1353


ATOM
1230
OE1
GLU
216
60.560
67.944
48.118
1.00
67.77

1DLC
1354


ATOM
1231
OE2
GLU
216
59.311
69.764
48.244
1.00
67.98

1DLC
1355


ATOM
1232
N
GLU
217
60.665
66.172
42.591
1.00
34.29

1DLC
1356


ATOM
1233
CA
GLU
217
61.682
65.750
41.623
1.00
33.05

1DLC
1357


ATOM
1234
C
GLU
217
61.440
66.442
40.282
1.00
33.15

1DLC
1358


ATOM
1235
O
GLU
217
62.376
66.884
39.619
1.00
34.29

1DLC
1359


ATOM
1236
CB
GLU
217
61.617
64.238
41.385
1.00
36.76

1DLC
1360


ATOM
1237
CG
GLU
217
61.993
63.362
42.565
1.00
36.91

1DLC
1361


ATOM
1238
CD
GLU
217
62.121
61.887
42.182
1.00
39.24

1DLC
1362


ATOM
1239
OE1
GLU
217
61.938
61.540
40.993
1.00
37.21

1DLC
1363


ATOM
1240
OE2
GLU
217
62.416
61.067
43.074
1.00
42.79

1DLC
1364


ATOM
1241
N
TRP
218
60.172
66.488
39.878
1.00
31.27

1DLC
1365


ATOM
1242
CA
TRP
218
59.756
67.116
38.627
1.00
25.69

1DLC
1366


ATOM
1243
C
TRP
218
59.846
68.638
38.714
1.00
22.53

1DLC
1367


ATOM
1244
O
TRP
218
59.670
69.330
37.722
1.00
23.72

1DLC
1368


ATOM
1245
CB
TRP
218
58.312
66.720
38.282
1.00
26.69

1DLC
1369


ATOM
1246
CG
TRP
218
58.097
65.248
37.980
1.00
26.77

1DLC
1370


ATOM
1247
CD1
TRP
218
59.051
64.322
37.664
1.00
28.09

1DLC
1371


ATOM
1248
CD2
TRP
218
56.840
64.549
37.961
1.00
25.69

1DLC
1372


ATOM
1249
NE1
TRP
218
58.468
63.093
37.449
1.00
28.06

1DLC
1373


ATOM
1250
CE2
TRP
218
57.114
63.203
37.626
1.00
26.57

1DLC
1374


ATOM
1251
CE3
TRP
218
55.512
64.929
38.196
1.00
22.74

1DLC
1375


ATOM
1252
CZ2
TRP
218
56.102
62.235
37.519
1.00
25.71

1DLC
1376


ATOM
1253
CZ3
TRP
218
54.511
63.967
38.089
1.00
21.96

1DLC
1377


ATOM
1254
CH2
TRP
218
54.813
62.637
37.755
1.00
22.35

1DLC
1378


ATOM
1255
N
GLY
219
60.088
69.160
39.910
1.00
21.50

1DLC
1379


ATOM
1256
CA
GLY
219
60.192
70.595
40.068
1.00
22.27

1DLC
1380


ATOM
1257
C
GLY
219
58.871
71.338
40.117
1.00
27.62

1DLC
1381


ATOM
1258
O
GLY
219
58.757
72.444
39.593
1.00
31.08

1DLC
1382


ATOM
1259
N
TYR
220
57.852
70.712
40.696
1.00
30.00

1DLC
1383


ATOM
1260
CA
TYR
220
56.543
71.343
40.843
1.00
26.76

1DLC
13B4


ATOM
1261
C
TYR
220
56.611
72.221
42.088
1.00
28.73

1DLC
1385


ATOM
1262
O
TYR
220
57.304
71.886
43.054
1.00
27.48

1DLC
1386


ATOM
1263
CR
TYR
220
55.453
70.289
41.076
1.00
27.42

1DLC
1387


ATOM
1264
CO
TYR
220
54.625
69.913
39.873
1.00
23.12

1DLC
1388


ATOM
1265
CD1
TYR
220
53.951
70.881
39.130
1.00
21.42

1DLC
1389


ATOM
1266
CD2
TYR
220
54.487
68.576
39.496
1.00
23.42

1DLC
1390


ATOM
1267
CE1
TYR
220
53.152
70.521
38.034
1.00
22.62

1DLC
1391


ATOM
1268
CE2
TYR
220
53.698
68.207
38.413
1.00
20.38

1DLC
1392


ATOM
1269
CZ 
TYR
220
53.033
69.178
37.685
1.00
22.10

1DLC
1393


ATOM
1270
OH 
TYR
220
52.252
68.802
36.617
1.00
23.88

1DLC
1394


ATOM
1271
N
GLU
221
55.870
73.324
42.080
1.00
30.82

1DLC
1395


ATOM
1272
CA
GLU
221
55.825
74.225
43.233
1.00
32.66

1DLC
1396


ATOM
1273
C
GLU
221
55.123
73.517
44.398
1.00
30.03

1DLC
1397


ATOM
1274
O
GLU
221
54.287
72.638
44.182
1.00
27.72

1DLC
1398


ATOM
1275
CR
GLU
221
55.023
75.492
42.894
1.00
38.56

1DLC
1399


ATOM
1276
CG
GLU
221
55.470
76.271
41.656
1.00
43.49

1DLC
1400


ATOM
1277
CD
GLU
221
56.855
76.898
41.791
1.00
48.97

1DLC
1401


ATOM
1278
OE1
GLU
221
57.330
77.133
42.935
1.00
48.86

1DLC
1402


ATOM
1279
OE2
GLU
221
57.468
77.163
40.730
1.00
52.79

1DLC
1403


ATOM
1280
N
LYS
222
55.454
73.909
45.624
1.00
30.89

1DLC
1404


ATOM
1281
CA
LYS
222
54.823
73.341
46.823
1.00
33.36

1DLC
1405


ATOM
1282
C
LYS
222
53.298
73.481
46.711
1.00
33.05

1DLC
1406


ATOM
1283
O
LYS
222
52.553
72.577
47.082
1.00
33.57

1DLC
1407


ATOM
1204
CB
LYS
222
55.281
74.096
48.072
1.00
36.59

1DLC
1408


ATOM
1205
CG
LYS
222
56.696
73.829
48.528
1.00
41.95

1DLC
1409


ATOM
1286
CD
LYS
222
56.774
72.524
49.300
1.00
52.08

1DLC
1410


ATOM
1287
CE
LYS
222
57.623
72.678
50.563
1.00
56.91

1DLC
1411


ATOM
1288
NZ
LYS
222
57.030
73.645
51.546
1.00
59.58

1DLC
1412


ATOM
1289
N
GLU
223
52.865
74.631
46.188
1.00
31.86

1DLC
1413


ATOM
1290
CA
GLU
223
51.453
74.964
45.985
1.00
30.30

1DLC
1414


ATOM
1291
C
GLU
223
50.767
74.012
45.016
1.00
28.77

1DLC
1415


ATOM
1292
O
GLU
223
49.592
73.689
45.192
1.00
30.14

1DLC
1416


ATOM
1293
CR
GLU
223
51.303
76.382
45.430
1.00
32.15

1DLC
1417


ATOM
1294
CG
GLU
223
51.827
77.493
46.326
1.00
39.10

1DLC
1410


ATOM
1295
CD
GLU
223
53.302
77.826
46.105
1.00
39.68

1DLC
1419


ATOM
1296
OE1
GLU
223
53.980
77.137
45.315
1.00
36.48

1DLC
1420


ATOM
1297
OE2
GLU
223
53.777
78.807
46.719
1.00
44.29

1DLC
1421


ATOM
1298
N
ASP
224
51.488
73.622
43.964
1.00
26.06

1DLC
1422


ATOM
1299
CA
ASP
224
50.975
72.702
42.946
1.00
26.67

1DLC
1423


ATOM
1300
C
ASP
224
50.699
71.311
43.509
1.00
25.47

1DLC
1424


ATOM
1301
O
ASP
224
49.610
70.763
43.347
1.00
26.25

1DLC
1425


ATOM
1302
CB
ASP
224
51.964
72.578
41.787
1.00
29.40

1DLC
1426


ATOM
1303
CG
ASP
224
52.088
73.860
40.979
1.00
38.45

1DLC
1427


ATOM
1304
OD1
ASP
224
51.145
74.677
40.990
1.00
38.89

101.C
1428


ATOM
1305
OD2
ASP
224
53.134
74.052
40.319
1.00
45.08

1DLC
1429


ATOM
1306
N
ILE
225
51.684
70.762
44.205
1.00
21.39

1DLC
1430


ATOM
1307
CA
ILE
225
51.565
69.439
44.792
1.00
21.79

1DLC
1431


ATOM
1306
C
ILE
225
50.400
69.397
45.784
1.00
20.00

1DLC
1432


ATOM
1309
O
ILE
225
49.636
68.438
45.813
1.00
19.14

1DLC
1433


ATOM
1310
CB
ILE
225
52.901
69.030
45.465
1.00
20.50

1DLC
1434


ATOM
1311
CG1
ILE
225
54.034
69.121
44.438
1.00
21.29

1DLC
1435


ATOM
1312
CG2
ILE
225
52.819
67.608
46.001
1.00
20.23

1DLC
1436


ATOM
1313
CD1
ILE
225
55.407
69.056
45.037
1.00
21.75

1DLC
1437


ATOM
1314
N
ALA
226
50.239
70.479
46.538
1.00
19.79

1DLC
1438


ATOM
1315
CA
ALA
226
49.166
70.610
47.524
1.00
20.24

1DLC
1439


ATOM
1316
C
ALA
226
47.782
70.704
46.854
1.00
21.11

1DLC
1440


ATOM
1317
O
ALA
226
46.799
70.134
47.341
1.00
18.19

1DLC
1441


ATOM
1318
CB
ALA
226
49.414
71.836
48.403
1.00
16.06

1DLC
1442


ATOM
1319
N
GLU
227
47.711
71.436
45.744
1.00
19.52

1DLC
1443


ATOM
1320
CA
GLU
227
46.460
71.572
45.019
1.00
19.61

1DLC
1444


ATOM
1321
C
GLU
227
46.075
70.210
44.465
1.00
21.10

1DLC
1445


ATOM
1322
O
GLU
227
44.900
69.838
44.492
1.00
26.53

1DLC
1446


ATOM
1323
CB
GLU
227
46.584
72.584
43.885
1.00
19.91

1DLC
1447


ATOM
1324
CG
GLU
227
45.303
72.736
43.075
1.00
21.72

1DLC
1448


ATOM
1325
CD
GLU
227
45.385
73.811
42.014
1.00
26.65

1DLC
1449


ATOM
1326
OE1
GLU
227
46.212
74.736
42.159
1.00
30.03

1DLC
1450


ATOM
1327
OE2
GLU
227
44.613
73.734
41.033
1.00
27.79

1DLC
1451


ATOM
1328
N
PHE
228
47.068
69.460
43.987
1.00
20.19

1DLC
1452


ATOM
1329
CA
PHE
228
46.832
68.114
43.456
1.00
18.86

1DLC
1453


ATOM
1330
C
PHE
228
46.335
67.182
44.569
1.00
19.65

1DLC
1454


ATOM
1331
O
PHE
228
45.418
66.387
44.361
1.00
20.81

1DLC
1455


ATOM
1332
CB
PHE
228
48.102
67.523
42.832
1.00
15.98

1DLC
1456


ATOM
1333
CG
PHE
228
48.416
68.035
41.445
1.00
14.18

1DLC
1457


ATOM
1334
CD1
PRE
228
47.425
68.103
40.466
1.00
9.27

1DLC
1458


ATOM
1335
CD2
PHE
228
49.726
68.404
41.108
1.00
12.83

1DLC
1459


ATOM
1336
CE1
PHE
228
47.729
68.523
39.178
1.00
8.69

1DLC
1460


ATOM
1337
CE2
PHE
228
50.047
68.829
39.816
1.00
9.25

1DLC
1461


ATOM
1338
CZ 
PHE
228
49.049
68.887
38.849
1.00
13.45

1DLC
1462


ATOM
1339
N
TYR
229
46.919
67.297
45.757
1.00
17.04

1DLC
1463


ATOM
1340
CA
TYR
229
46.503
66.451
46.867
1.00
17.31

1DLC
1464


ATOM
1341
C
TYR
229
45.048
66.729
47.261
1.00
20.11

1DLC
1465


ATOM
1342
O
TYR
229
44.249
65.798
47.369
1.00
23.73

1DLC
1466


ATOM
1343
CB
TYR
229
47.426
66.625
48.072
1.00
13.52

1DLC
1467


ATOM
1344
CG
TYR
229
47.095
65.691
49.217
1.00
10.64

1DLC
1468


ATOM
1345
CD1
TYR
229
47.277
64.319
49.094
1.00
9.77

1DLC
1469


ATOM
1346
CD2
TYR
229
46.575
66.178
50.412
1.00
10.19

1DLC
1470


ATOM
1347
CE1
TYR
229
46.947
63.455
50.131
1.00
9.80

1DLC
1471


ATOM
1348
CE2
TYR
229
46.242
65.320
51.453
1.00
12.10

1DLC
1472


ATOM
1349
CZ
TYR
229
46.431
63.961
51.304
1.00
11.99

1DLC
1473


ATOM
1350
OH 
TYR
229
46.106
63.107
52.330
1.00
16.85

1DLC
1474


ATOM
1351
N
LYS
230
44.693
67.998
47.462
1.00
19.47

1DLC
1475


ATOM
1352
CA
LYS
230
43.313
68.326
47.815
1.00
19.61

1DLC
1476


ATOM
1353
C
LYS
230
42.357
67.868
46.723
1.00
19.13

1DLC
1477


ATOM
1354
O
LYS
230
41.259
67.382
47.008
1.00
20.93

1DLC
1478


ATOM
1355
CR
LYS
230
43.137
69.812
48.083
1.00
17.36

1DLC
1479


ATOM
1356
CO 
LYS
230
43.786
70.262
49.367
1.00
22.08

1DLC
1480


ATOM
1357
CD
LYS
230
43.346
71.657
49.735
1.00
22.71

1DLC
1481


ATOM
1358
CE
LYS
230
41.854
71.690
49.992
1.00
22.53

1DLC
1482


ATOM
1359
NZ
LYS
230
41.408
73.051
50.364
1.00
25.70

1DLC
1483


ATOM
1360
N
ARG
231
42.794
67.975
45.474
1.00
15.74

1DLC
1484


ATOM
1361
CA
ARG
231
41.972
67.527
44.366
1.00
16.22

1DLC
1485


ATOM
1362
C
ARG
231
41.786
66.011
44.455
1.00
17.99

1DLC
1486


ATOM
1363
O
ARG
231
40.698
65.508
44.202
1.00
20.26

1DLC
1487


ATOM
1364
CB
ARG
231
42.615
67.904
43.033
1.00
20.80

1DLC
1488


ATOM
1365
CG
ARG
231
41.890
67.346
41.811
1.00
20.81

1DLC
1489


ATOM
1365
CD
ARG
231
42.356
68.028
40.534
1.00
25.62

1DLC
1490


ATOM
1367
NE 
ARG
231
42.219
69.481
40.616
1.00
25.19

1DLC
1491


ATOM
1368
CZ 
ARG
231
43.158
70.346
40.247
1.00
24.34

1DLC
1492


ATOM
1369
NH1
ARG
231
44.314
69.913
39.760
1.00
25.84

1DLC
1493


ATOM
1370
NH2
ARG
231
42.947
71.648
40.390
1.00
23.15

1DLC
1494


ATOM
1371
N
GLN
232
42.838
65.293
44.852
1.00
16.37

1DLC
1495


ATOM
1372
CA
GLN
232
42.779
63.840
44.982
1.00
14.65

1DLC
1496


ATOM
1373
C
GLN
232
41.786
63.422
46.068
1.00
16.33

1DLC
1497


ATOM
1374
O
GLN
232
41.011
62.491
45.883
1.00
19.48

1DLC
1498


ATOM
1375
CB
GLN
232
44.160
63.255
45.289
1.00
13.62

1DLC
1499


ATOM
1376
CG
GLN
232
44.250
61.761
45.006
1.00
16.45

1DLC
1500


ATOM
1377
CD
GLN
232
45.507
61.102
45.540
1.00
18.66

1DLC
1501


ATOM
1378
OE1
GLN
232
45.465
59.968
46.006
1.00
21.82

1DLC
1502


ATOM
1379
NE2
GLN
232
46.631
61.797
45.468
1.00
17.44

1DLC
1503


ATOM
1380
N
LEU
233
41.812
64.114
47.201
1.00
13.18

1DLC
1504


ATOM
1381
CA
LEU
233
40.888
63.820
48.289
1.00
15.87

1DLC
1505


ATOM
1382
C
LEU
233
39.427
64.066
47.879
1.00
17.22

1DLC
1506


ATOM
1383
O
LEU
233
38.549
63.248
48.1.57
1.00
22.21

1DLC
1507


ATOM
1384
CR
LEU
233
41.209
64.679
49.507
1.00
14.55

1DLC
1508


ATOM
1385
CG
LEU
233
42.582
64.520
50.148
1.00
18.77

1DLC
1509


ATOM
1386
CD1
LEU
233
42.837
65.712
51.054
1.00
21.30

1DLC
1510


ATOM
1387
CD2
LEU
233
42.664
63.219
50.918
1.00
17.59

1DLC
1511


ATOM
1388
N
LYS
234
39.166
65.191
47.222
1.00
16.53

1DLC
1512


ATOM
1389
CA
LYS
234
37.811
65.604
46.802
1.00
17.73

1DLC
1513


ATOM
1390
C
LYS
234
37.280
64.450
45.831
1.00
18.98

1DLC
1514


ATOM
1391
O
LYS
234
36.177
63.925
46.003
1.00
20.56

1DLC
1515


ATOM
1392
CB
LYS
234
37.748
66.882
46.145
1.00
19.54

1DLC
1516


ATOM
1393
CO
LYS
234
36.316
67.360
45.891
1.00
30.78

1DLC
1517


ATOM
1394
CD
LYS
234
36.236
68.364
44.747
1.00
39.43

1DLC
1518


ATOM
1395
CE
LYS
234
36.703
67.727
43.433
1.00
48.46

1DLC
1519


ATOM
1396
NZ
LYS
234
35.739
68.660
42.257
1.00
52.24

1DLC
1520


ATOM
1397
N
LEU
235
38.080
64.119
44.825
1.00
19.47

1DLC
1521


ATOM
1398
CA
LEU
235
37.677
63.142
43.826
1.00
16.47

1DLC
1522


ATOM
1399
C
LEU
235
37.536
61.714
44.346
1.00
16.10

1DLC
1523


ATOM
1400
O
LEU
235
36.694
60.961
41.862
1.00
19.12

1DLC
1524


ATOM
1401
CB
LEU
235
38.593
63.224
42.604
1.00
17.24

1DLC
1525


ATOM
1402
CG
LEU
235
38.518
64.594
41.903
1.00
18.14

1DLC
1526


ATOM
1403
CD1
LEU
235
39.500
64.684
40.746
1.00
17.32

1DLC
1527


ATOM
1404
CD2
LEO
235
37.100
64.843
41.415
1.00
19.19

1DLC
1528


ATOM
1405
N
THR
236
38.324
61.337
45.347
1.00
15.47

1DLC
1529


ATOM
1406
CA
THR
236
38.200
59.988
45.915
1.00
16.87

1DLC
1530


ATOM
1407
C
THR
236
36.816
59.809
46.545
1.00
16.35

1DLC
1531


ATOM
1408
O
THR
236
36.196
58.763
46.418
1.00
16.83

1DLC
1532


ATOM
1409
CB
THR
236
39.284
59.705
46.966
1.00
15.64

1DLC
1531


ATOM
1410
CG1
THR
236
40.562
59.726
46.323
1.00
21.58

1DLC
1534


ATOM
1411
CG2
THR
236
39.073
58.337
47.618
1.00
11.02

1DLC
1535


ATOM
1412
N
GLN
237
36.333
60.845
47.216
1.00
16.17

1DLC
1536


ATOM
1413
CA
GLN
237
35.014
60.821
47.830
1.00
15.51

1DLC
1537


ATOM
1414
C
GLN
237
33.905
60.798
46.748
1.00
17.21

1DLC
1538


ATOM
1415
O
GLN
237
33.015
59.944
46.773
1.00
16.26

1DLC
1539


ATOM
1416
CB
GLN
237
34.881
62.037
48.751
1.00
16.03

1DLC
1540


ATOM
1417
CG
GLN
237
33.537
62.217
49.423
1.00
21.22

1DLC
1541


ATOM
1418
CD
GLN
237
32.598
63.054
48.596
1.00
25.16

1DLC
1542


ATOM
1419
OE1
GLN
237
32.760
64.265
48.486
1.00
27.94

1DLC
1543


ATOM
1420
NE2
GLN
237
31.633
62.411
47.969
1.00
27.25

1DLC
1544


ATOM
1421
N
GLU
238
33.998
61.704
45.776
1.00
18.54

1DLC
1545


ATOM
1422
CA
GLU
238
33.016
61.807
44.693
1.00
19.10

1DLC
1546


ATOM
1423
C
GLU
238
32.901
60.561
43.626
1.00
19.60

1DLC
1547


ATOM
1424
O
GLU
238
31.802
60.063
43.564
1.00
22.82

1DLC
1548


ATOM
1425
CB
GLU
238
33.326
63.001
43.789
1.00
20.79

1DLC
1549


ATOM
1426
CG
GLU
238
33.126
64.348
44.446
1.00
32.20

1DLC
1550


ATOM
1427
CD
GLU
238
33.403
65.518
43.513
1.00
38.00

1DLC
1551


ATOM
1428
OE1
GLU
238
33.582
65.314
42.283
1.00
38.36

1DLC
1SS2


ATOM
1429
OE2
GLU
238
33.434
66.657
44.028
1.00
45.77

1DLC
1553


ATOM
1430
N
TYR
239
34.032
60.082
43.328
1.00
17.99

1DLC
1554


ATOM
1431
CA
TYR
239
34.041
58.899
42.481
1.00
16.20

1DLC
1555


ATOM
1432
C
TYR
239
33.495
57.670
43.212
1.00
15.23

1DLC
1556


ATOM
1433
O
TYR
239
32.726
56.900
42.652
1.00
15.80

1DLC
1557


ATOM
1434
CB
TYR
239
35.455
58.646
41.965
1.00
18.91

1DLC
1558


ATOM
1435
CO
TYR
239
35.987
59.715
41.022
1.00
15.91

1DLC
1559


ATOM
1436
CD1
TYR
239
35.124
60.541
40.304
1.00
14.94

1DLC
1560


ATOM
1437
CD2
TYR
239
37.357
59.844
40.794
1.00
18.81

1DLC
1561


ATOM
1438
OE1
TYR
239
35.612
61.455
39.375
1.00
12.13

1DLC
1562


ATOM
1439
OE2
TYR
239
37.853
60.756
39.863
1.00
15.85

1DLC
1563


ATOM
1440
CZ 
TYR
239
36.978
61.552
39.155
1.00
13.69

1DLC
1564


ATOM
1441
OH 
TYR
239
37.468
62.392
38.181
1.00
16.58

1DLC
1565


ATOM
1442
N
THR
240
33.849
57.529
44.486
1.00
17.13

1DLC
1566


ATOM
1443
CA
THR
240
33.365
56.406
45.296
1.00
14.37

1DLC
1557


ATOM
1444
C
THR
240
31.878
56.494
45.457
1.00
16.34

1DLC
1568


ATOM
1445
O
THR
240
31.155
55.554
45.126
1.00
17.60

1DLC
1569


ATOM
1446
CB
THR
240
34.041
56.398
46.701
1.00
17.40

1DLC
1570


ATOM
1447
OG1
THR
240
35.450
56.166
46.573
1.00
22.45

1DLC
1571


ATOM
1448
CO2
THR
240
33.436
55.308
47.585
1.00
14.03

1DLC
1572


ATOM
1449
N
ASP
241
31.406
57.637
45.946
1.00
16.35

1DLC
1573


ATOM
1450
CA
ASP
241
29.977
57.844
46.145
1.00
13.45

1DLC
1574


ATOM
1451
C
ASP
241
29.170
57.692
44.863
1.00
15.38

1DLC
1575


ATOM
1452
O
ASP
241
28.119
57.051
44.862
1.00
21.27

1DLC
1576


ATOM
1453
CB
ASP
241
29.709
59.192
46.813
1.00
12.03

1DLC
1577


ATOM
1454
CG
ASP
241
30.062
59.192
48.290
1.00
10.13

1DLC
1576


ATOM
1455
OD1
ASP
241
30.272
58.107
46.864
1.00
15.38

1DLC
1579


ATOM
1456
OD2
ASP
241
30.122
60.277
48.890
1.00
14.27

1DLC
1580


ATOM
1457
N
HIS
242
29.692
58.205
43.757
1.00
14.94

1DLC
1581


ATOM
1458
CA
HIS
242
28.996
58.082
42.487
1.00
15.39

1DLC
1582


ATOM
1459
C
HIS
242
28.766
56.608
42.139
1.00
17.79

1DLC
1583


ATOM
1460
O
HIS
242
27.659
56.214
41.793
1.00
22.62

1DLC
1584


ATOM
1461
CB
HIS
242
29.781
58.772
41.360
1.00
15.91

1DLC
1585


ATOM
1462
CG
HIS
242
29.170
58.600
39.997
1.00
17.44

1DLC
1586


ATOM
1463
ND1
HIS
242
28.285
59.508
39.454
1.00
20.18

1DLC
1587


ATOM
1464
CD2
HIS
242
29.320
57.623
39.069
1.00
17.90

1DLC
1588


ATOM
1465
CE1
HIS
242
27.916
59.100
38.251
1.00
16.84

1DLC
1569


ATOM
1466
NE2
HIS
242
28.530
57.958
37.995
1.00
20.33

1DLC
1590


ATOM
1467
N
CYS
243
29.804
55.793
42.262
1.00
17.39

1DLC
1591


ATOM
1468
CA
CYS
243
29.694
54.377
41.924
1.00
17.86

1DLC
1592


ATOM
1469
C
CYS
243
28.721
53.588
42.776
1.00
17.12

1DLC
1593


ATOM
1470
O
CYS
243
27.939
52.800
42.251
1.00
21.15

1DLC
1594


ATOM
1471
CB
CYS
243
31.071
53.712
41.923
1.00
15.41

1DLC
1595


ATOM
1472
SG
CYS
243
32.126
54.356
40.620
1.00
18.63

1DLC
1596


ATOM
1473
N
VAL
244
28.742
53.812
44.083
1.00
17.77

1DLC
1597


ATOM
1474
CA
VAL
244
27.829
53.099
44.961
1.00
17.07

1DLC
1598


ATOM
1475
C
VAL
244
26.368
53.507
44.693
1.00
17.91

1DLC
1599


ATOM
1476
O
VAL
244
25.492
52.658
44.569
1.00
17.98

1DLC
1600


ATOM
1477
CB
VAL
244
28.185
53.318
46.434
1.00
16.68

1DLC
1601


ATOM
1478
CG1
VAL
244
27.179
52.611
47.319
1.00
15.45

1DLC
1602


ATOM
1479
CG2
VAL
244
29.582
52.804
46.711
1.00
11.35

1DLC
1603


ATOM
1480
N
LYS
245
26.129
54.805
44.551
1.00
19.29

1DLC
1604


ATOM
1481
CA
LYS
245
24.788
55.326
44.282
1.00
21.04

1DLC
1605


ATOM
1482
C
LYS
245
24.142
54.667
43.056
1.00
23.00

1DLC
1606


ATOM
1483
O
LYS
245
23.031
54.139
43.131
1.00
24.89

1DLC
1607


ATOM
1484
CR
LYS
245
24.855
56.837
44.073
1.00
21.68

1DLC
1608


ATOM
1485
CG
LYS
245
23.552
57.472
43.640
1.00
22.74

1DLC
1609


ATOM
1486
CD
LYS
245
23.779
58.929
43.268
1.00
30.91

1DLC
1610


ATOM
1487
CE
LYS
245
22.469
59.687
43.068
1.00
34.31

1DLC
1611


ATOM
1488
NZ
LYS
245
21.742
59.275
41.844
1.00
37.08

1DLC
1612


ATOM
1489
N
TRP
246
24.848
54.582
41.930
1.00
20.59

1DLC
1613


ATOM
1490
CA
TRP
246
24.332
54.088
40.701
1.00
19.32

1DLC
1614


ATOM
1491
C
TRP
246
24.386
52.568
40.685
1.00
21.56

1DLC
1615


ATOM
1492
O
TRP
246
23.604
51.918
39.983
1.00
23.26

1DLC
1616


ATOM
1493
CB
TRP
246
25.026
54.695
39.489
1.00
16.97

1DLC
1617


ATOM
1494
CG
TRP
246
24.705
56.132
39.400
1.00
20.83

1DLC
1616


ATOM
1495
CD1
TRP
246
25.528
57.179
39.697
1.00
22.17

1DLC
1619


ATOM
1496
CD2
TRP
246
23.427
56.697
39.096
1.00
21.29

1DLC
1620


ATOM
1497
NE1
TRP
246
24.837
58.361
39.609
1.00
24.09

1DLC
1621


ATOM
1498
CE2
TRP
246
23.546
58.097
39.239
1.00
23.54

1DLC
1622


ATOM
1499
CE3
TRP
246
22.191
56.157
38.722
1.00
20.29

1DLC
1623


ATOM
1500
CZ2
TRP
246
22.473
58.966
39.021
1.00
23.70

1DLC
1624


ATOM
1501
CZ3
TRP
246
21.127
57.017
38.507
1.00
22.34

1DLC
1625


ATOM
1502
CH2
TRP
246
21.274
58.410
38.657
1.00
23.62

1DLC
1626


ATOM
1503
N
TYR
247
25.304
51.997
41.460
1.00
20.03

1DLC
1627


ATOM
1504
CA
TYR
247
25.385
50.549
41.558
1.00
20.17

1DLC
1628


ATOM
1505
C
TYR
247
24.034
50.088
42.133
1.00
19.37

1DLC
1629


ATOM
1506
O
TYR
247
23.360
49.230
41.561
1.00
19.35

1DLC
1630


ATOM
1507
CB
TYR
247
26.528
50.121
42.494
1.00
17.68

1DLC
1631


ATOM
1508
CG
TYR
247
26.392
48.689
42.957
1.00
13.41

1DLC
1632


ATOM
1S09
CD1
TYR
247
26.579
47.633
42.067
1.00
14.48

1DLC
1633


ATOM
1510
CD2
TYR
247
25.966
48.398
44.247
1.00
11.29

1DLC
1634


ATOM
1511
CE1
TYR
247
26.331
46.325
42.446
1.00
14.18

1DLC
1635


ATOM
1512
CE2
TYR
247
25.714
47.096
44.637
1.00
13.99

1DLC
1636


ATOM
1513
CZ 
TYR
247
25.892
46.063
43.729
1.00
16.05

1DLC
1637


ATOM
1514
OH 
TYR
247
25.586
44.773
44.087
1.00
19.99

1DLC
1638


ATOM
1515
N
ASN
248
23.634
50.709
43.243
1.00
16.91

1DLC
1639


ATOM
1516
CA
ASN
248
22.373
50.393
43.905
1.00
19.32

1DLC
1640


ATOM
1517
C
ASN
248
21.147
50.687
43.031
1.00
19.33

1DLC
1641


ATOM
1518
O
ASN
248
20.169
49.939
43.050
1.00
18.74

1DLC
1642


ATOM
1519
CD
ASN
248
22.276
51.116
45.250
1.00
18.47

1DLC
1643


ATOM
1520
CO 
ASN
248
23.141
50.471
46.315
1.00
23.55

1DLC
1644


ATOM
1521
OD1
ASN
248
23.184
49.249
46.438
1.00
28.32

1DLC
1645


ATOM
1522
ND2
ASN
248
23.844
51.284
47.081
1.00
24.45

1DLC
1646


ATOM
1523
N
VAL
249
21.207
51.763
42.253
1.00
17.79

1DLC
1647


ATOM
1524
CA
VAL
249
20.105
52.103
41.366
1.00
16.98

1DLC
1648


ATOM
1525
C
VAL
249
19.883
50.921
40.422
1.00
19.97

1DLC
1649


ATOM
1526
O
VAL
249
18.763
50.425
40.284
1.00
22.20

1DLC
1650


ATOM
1527
CB
VAL
249
20.403
53.384
40.550
1.00
15.18

1DLC
1651


ATOM
1528
CG1
VAL
249
19.374
53.566
39.445
1.00
8.38

1DLC
1652


ATOM
1529
CG2
VAL
249
20.399
54.596
41.467
1.00
12.81

1DLC
1653


ATOM
1530
N
GLY
250
20.970
50.431
39.834
1.00
19.71

1DLC
1654


ATOM
1531
CA
GLY
250
20.879
49.304
38.924
1.00
20.85

1DLC
1655


ATOM
1532
C
GLY
250
20.409
48.035
39.609
1.00
22.20

1DLC
1656


ATOM
1533
O
GLY
250
19.558
47.316
39.089
1.00
26.29

1DLC
1657


ATOM
1534
N
LET
251
20.935
47.772
40.797
1.00
20.95

1DLC
1658


ATOM
1535
CA
LEU
251
20.554
46.594
41.563
1.00
20.76

1DLC
1659


ATOM
1536
C
LEO
251
19.031
46.532
41.792
1.00
22.33

1DLC
1660


ATOM
1537
O
LEU
251
18.386
45.516
41.502
1.00
21.83

1DLC
1661


ATOM
1538
CB
LEU
251
21.299
46.597
42.900
1.00
17.68

1DLC
1662


ATOM
1539
CG
LEU
251
21.274
45.306
43.716
1.00
19.56

1DLC
1663


ATOM
1540
CD1
LEU
251
21.908
44.160
42.937
1.00
16.74

1DLC
1664


ATOM
1541
CD2
LEU
251
22.002
45.537
45.009
1.00
16.93

1DLC
1665


ATOM
1542
N
ASP
252
18.463
47.629
42.287
1.00
25.34

1DLC
1666


ATOM
1543
CA
ASP
252
17.023
47.721
42.548
1.00
26.45

1DLC
1667


ATOM
1544
C
ASP
252
16.172
47.589
41.288
1.00
29.16

1DLC
1668


ATOM
1545
O
ASP
252
15.089
47.015
41.322
1.00
32.76

1DLC
1669


ATOM
1546
CB
ASP
252
16.684
49.029
43.257
1.00
28.64

1DLC
1670


ATOM
1547
CG
ASP
252
17.192
49.071
44.686
1.00
35.67

1DLC
1671


ATOM
1548
OD1
ASP
252
17.305
48.002
45.331
1.00
40.98

1DLC
1672


ATOM
1549
OD2
ASP
252
17.476
50.184
45.170
1.00
42.32

1DLC
1673


ATOM
1550
N
LYS
253
16.673
48.100
40.173
1.00
26.89

1DLC
1674


ATOM
1551
CA
LYS
253
15.953
48.009
38.916
1.00
27.76

1DLC
1675


ATOM
1652
C
LYS
251
15.801
46.549
38.449
1.00
27.94

1DLC
1676


ATOM
1553
O
LYS
253
14.893
46.226
37.692
1.00
33.46

1DLC
1677


ATOM
1554
CB
LYS
253
16.664
48.854
37.854
1.00
31.20

1DLC
1678


ATOM
1555
CG
LYS
253
15.927
48.957
36.523
1.00
41.11

1DLC
1679


ATOM
1556
CD
LYS
253
16.574
49.982
35.592
1.00
49.37

1DLC
1680


ATOM
1557
CE
LYS
253
16.569
51.381
36.206
1.00
55.35

1DLC
1681


ATOM
1558
NZ
LYS
253
17.234
52.399
35.335
1.00
58.91

1DLC
1682


ATOM
1559
N
LEO
254
16.674
45.662
18.915
1.00
26.78

1DLC
1683


ATOM
1560
CA
LEU
254
16.619
44.251
38.521
1.00
24.25

1DLC
1684


ATOM
1561
C
LEU
254
15.876
43.317
39.487
1.00
25.28

1DLC
1665


ATOM
1562
O
LEO
254
15.695
42.129
39.197
1.00
24.46

1DLC
1686


ATOM
1563
CB
LEO
254
18.027
43.713
38.289
1.00
22.43

1DLC
1687


ATOM
1564
CG
LEO
254
18.834
44.386
37.191
1.00
21.13

1DLC
1688


ATOM
1565
CD1
LEU
254
20.199
43.748
37.114
1.00
19.25

1DLC
1689


ATOM
1566
CD2
LEO
254
18.114
44.247
35.975
1.00
18.91

1DLC
1690


ATOM
1567
N
ARG
255
15.460
43.837
40.634
1.00
24.30

1DLC
1691


ATOM
1568
CA
ARG
255
14.738
43.018
41.598
1.00
26.66

1DLC
1692


ATOM
1569
C
ARG
255
13.400
42.587
41.003
1.00
26.42

1DLC
1693


ATOM
1570
O
ARG
255
12.638
43.406
40.497
1.00
28.64

1DLC
1694


ATOM
1571
CB
ARG
255
14.494
43.782
42.893
1.00
27.60

1DLC
1695


ATOM
1572
CG
ARG
255
15.646
44.655
43.323
1.00
35.20

1DLC
1696


ATOM
1573
CD
ARG
255
15.438
45.138
44.737
1.00
35.77

1DLC
1697


ATOM
1574
NE
ARG
255
15.670
44.042
45.666
1.00
40.94

1DLC
1698


ATOM
1575
CZ 
ARG
255
16.779
43.903
46.381
1.00
41.53

1DLC
1699


ATOM
1576
NH1
ARG
255
17.749
44.804
46.279
1.00
43.27

1DLC
1700


ATOM
1577
NH2
ARG
255
16.940
42.839
47.153
1.00
41.04

1DLC
1701


ATOM
1578
N
GLY
256
13.132
41.291
41.043
1.00
25.67

1DLC
1702


ATOM
1579
CA
GLY
256
11.893
40.777
40.502
1.00
21.48

1DLC
1703


ATOM
1580
C
GLY
256
11.314
39.735
41.428
1.00
22.34

1DLC
1704


ATOM
1581
O
GLY
256
11.690
39.653
42.600
1.00
22.71

1DLC
1705


ATOM
1582
N
SER
257
10.401
38.927
40.907
1.00
22.70

1DLC
1706


ATOM
1583
CA
SER
257
9.766
37.885
41.708
1.00
22.19

1DLC
1707


ATOM
1584
C
SER
257
10.123
36.504
41.191
1.00
19.96

1DLC
1708


ATOM
1585
O
SER
257
10.073
35.527
41.928
1.00
22.04

1DLC
1709


ATOM
1586
CB
GER
257
8.240
36.045
41.690
1.00
22.99

1DLC
1710


ATOM
1587
OG
SER
257
7.714
37.784
40.395
1.00
26.85

1DLC
1711


ATOM
1588
N
SER
258
10.488
36.427
39.920
1.00
18.79

1DLC
1712


ATOM
1589
CA
SER
258
10.835
35.154
39.311
1.00
20.57

1DLC
1713


ATOM
1590
C
SER
258
12.277
34.694
39.511
1.00
22.33

1DLC
1714


ATOM
1591
O
SER
258
13.156
35.462
39.895
1.00
24.89

1DLC
1715


ATOM
1592
CB
SER
258
10.544
35.191
37.809
1.00
19.52

1DLC
1716


ATOM
1593
OG 
SER
258
11.502
35.975
37.113
1.00
24.21

1DLC
1717


ATOM
1594
N
TYR
259
12.494
33.419
39.212
1.00
22.78

1DLC
1718


ATOM
1595
CA
TYR
269
13.799
32.787
39.281
1.00
23.11

1DLC
1719


ATOM
1596
C
TYR
259
14.714
33.449
38.243
1.00
25.26

1DLC
1720


ATOM
1597
O
TYR
259
15.901
33.677
38.490
1.00
26.66

1DLC
1721


ATOM
1598
CB
TYR
259
13.655
31.300
38.953
1.00
21.44

1DLC
1722


ATOM
1599
CG
TYR
259
14.959
30.627
38.663
1.00
21.31

1DLC
1723


ATOM
1600
CD1
TYR
259
15.812
30.253
39.698
1.00
22.67

1DLC
1724


ATOM
1601
CD2
TYR
259
15.369
30.411
37.351
1.00
19.37

1DLC
1725


ATOM
1602
CE1
TYR
259
17.045
29.682
39.432
1.00
23.31

1DLC
1726


ATOM
1603
CE2
TYR
259
16.592
29.847
37.078
1.00
21.89

1DLC
1727


ATOM
1604
CZ 
TYR
259
17.430
29.485
38.121
1.00
21.29

1DLC
1728


ATOM
1605
OH
TYR
259
18.655
28.932
37.850
1.00
26.88

1DLC
1729


ATOM
1606
N
GLU
260
14.154
33.732
37.073
1.00
21.58

1DLC
1730


ATOM
1607
CA
GLU
260
14.900
34.374
36.001
1.00
21.56

1DLC
1731


ATOM
1608
C
GLU
260
15.315
35.785
36.432
1.00
24.51

1DLC
1732


ATOM
1609
O
OLD
260
16.393
36.262
36.075
1.00
27.27

1DLC
1733


ATOM
1610
CB
GLU
260
14.064
34.432
34.723
1.00
20.53

1DLC
1734


ATOM
1611
CO
GLU
260
13.701
33.066
34.117
1.00
20.94

1DLC
1735


ATOM
1612
CD
GLU
260
12.625
32.287
34.881
1.00
23.83

1DLC
1736


ATOM
1613
OE1
GLU
260
11.805
32.886
35.616
1.00
27.07

1DLC
1737


ATOM
1614
OE2
GLU
260
12.593
31.051
34.743
1.00
26.90

1DLC
1738


ATOM
1615
N
SER
261
14.472
36.439
37.226
1.00
22.78

1DLC
1739


ATOM
1616
CA
SER
261
14.792
37.777
37.716
1.00
24.00

1DLC
1740


ATOM
1617
C
SER
261
16.020
37.733
38.617
1.00
22.5.3

1DLC
1741


ATOM
1618
O
SER
261
16.941
38.550
38.490
1.00
21.49

1DLC
1742


ATOM
1619
CB
SER
261
13.632
38.361
38.516
1.00
25.06

1DLC
1743


ATOM
1620
OG
SER
261
12.581
38.742
37.657
1.00
40.53

1DLC
1744


ATOM
1621
N
TRP
262
15.017
36.775
39.534
1.00
17.09

1DLC
1745


ATOM
1622
CA
TRP
262
17.125
36.627
40.450
1.00
19.88

1DLC
1746


ATOM
1623
C
TRP
262
18.464
36.306
39.770
1.00
18.85

1DLC
1747


ATOM
1624
O
TRP
262
19.496
36.795
40.213
1.00
22.45

1DLC
1748


ATOM
1625
CB
TRP
262
16.812
35.590
41.518
1.00
16.11

1DLC
1749


ATOM
1626
CG
TRP
262
17.835
35.588
42.585
1.00
17.10

1DLC
1750


ATOM
1627
CD1
TRP
262
17.807
36.307
43.745
1.00
17.25

1DLC
1751


ATOM
1628
CD2
TRP
262
19.065
34.852
42.593
1.00
17.80

1DLC
1752


ATOM
1629
NE1
TRP
262
18.943
36.061
44.476
1.00
18.81

1DLC
1753


ATOM
1630
CE2
TRP
262
19.735
35.175
43.794
1.00
18.51

1DLC
1754


ATOM
1631
CE3
TRP
262
19.668
33.951
41.699
1.00
15.16

1DLC
1755


ATOM
1632
CZ2
TRP
262
20.982
34.626
44.130
1.00
21.00

1DLC
1756


ATOM
1633
CZ3
TRP
262
20.906
33.406
42.029
1.00
15.42

1DLC
1757


ATOM
1634
CH2
TRP
262
21.550
33.745
43.235
1.00
19.20

1DLC
1758


ATOM
1635
N
VAL
263
18.456
35.502
38.709
1.00
19.89

1DLC
1759


ATOM
1636
CA
VAL
263
19.708
35.174
38.014
1.00
18.35

1DLC
1760


ATOM
1637
C
VAL
263
20.311
36.456
37.453
1.00
20.15

1DLC
1761


ATOM
1638
O
VAL
263
21.505
36.709
37.632
1.00
24.22

1DLC
1762


ATOM
1639
CB
VAL
263
19.528
34.097
36.887
1.00
18.77

1DLC
1763


ATOM
1640
CG1
VAL
263
20.859
33.850
36.151
1.00
12.43

1DLC
1764


ATOM
1641
CG2
VAL
263
19.042
32.778
37.488
1.00
14.72

1DLC
1765


ATOM
1642
N
ASN
264
19.474
37.289
56.838
1.00
19.11

1DLC
1766


ATOM
1643
CA
ASN
264
19.924
38.567
36.287
1.00
19.35

1DLC
1767


ATOM
1644
C
ASN
264
20.437
39.485
37.390
1.00
19.34

1DLC
1768


ATOM
1645
O
ASN
264
21.531
40.031
37.307
1.00
21.96

1DLC
1769


ATOM
1646
CB
ASN
264
18.784
39.256
35.563
1.00
24.05

1DLC
1770


ATOM
1647
CG
ASN
264
18.415
38.551
34.294
1.00
30.20

1DLC
1771


ATOM
1648
OD1
ASN
264
19.233
37.850
33.710
1.00
35.20

1DLC
1772


ATOM
1649
ND2
ASN
264
17.179
38.734
33.855
1.00
34.82

1DLC
1773


ATOM
1650
N
PHE
265
19.629
39.631
38.429
1.00
19.08

1DLC
1774


ATOM
1651
CA
PHE
265
19.941
40.445
39.594
1.00
16.55

1DLC
1775


ATOM
1652
C
PHE
265
21.318
40.065
40.165
1.00
17.77

1DLC
1776


ATOM
1653
O
PHE
265
22.194
40.914
40.321
1.00
19.27

1DLC
1777


ATOM
1654
CB
PHE
265
18.821
40.223
40.619
1.00
12.97

1DLC
1778


ATOM
1655
CG
PHE
265
19.066
40.831
41.971
1.00
10.89

1DLC
1779


ATOM
1656
CD1
PHE
265
18.677
42.137
42.241
1.00
13.68

1DLC
1780


ATOM
1657
CD2
PHE
265
19.574
40.059
43.010
1.00
9.55

1DLC
1.781


ATOM
1658
CE1
PHE
265
18.780
42.663
43.530
1.00
12.86

1DLC
1782


ATOM
1659
CE2
PHE
265
19.680
40.571
44.295
1.00
10.43

1DLC
1783


ATOM
1660
CZ 
PHE
265
19.281
41.876
44.559
1.00
10.95

1DLC
1784


ATOM
1661
N
ASN
266
21.518
38.773
40.403
1.00
19.03

1DLC
1785


ATOM
1662
CA
ASN
266
22.766
38.265
40.954
1.00
17.33

1DLC
1786


ATOM
1663
C
ASN 
266
23.957
32.336
39.992
1.00
17.92

1DLC
1787


ATOM
1664
O
ASN 
266
25.092
28.493
40.435
1.00
22.09

1DLC
1788


ATOM
1665
CB
ASN
266
22.584
36.840
41.468
1.00
15.11

1DLC
1789


ATOM
1666
CG
ASN
266
23.826
36.313
42.142
1.00
17.39

1DLC
1790


ATOM
1667
OD1
ASN
266
24.244
36.822
43.181
1.00
17.95

1DLC
1791


ATOM
1668
ND2
ASN 
266
24.444
35.307
41.543
1.00
18.20

1DLC
1792


ATOM
1669
N
ARG 
267
23.716
38.190
38.692
1.00
17.41

1DLC
1793


ATOM
1670
CA
ARG
267
24.801
38.283
37.707
1.00
17.83

1DLC
1794


ATOM
1671
C
ARG 
267
25.306
39.730
37.662
1.00
19.29

1DLC
1795


ATOM
1672
O
ARC 
267
26.505
39.976
31.578
1.00
20.96

1DLC
1796


ATOM
1673
CB
ARG
267
24.321
37.849
36.322
1.00
16.99

1DLC
1797


ATOM
1674
CG
ARG
267
25.377
37.917
35.248
1.00
17.92

1DLC
1798


ATOM
1675
CD
ARG 
267
24.824
37.461
33.916
1.00
22.41

1DLC
1799


ATOM
1676
NE 
ARC 
267
24.427
36.052
33.942
1.00
35.91

1DLC
1800


ATOM
1677
CZ 
ARO 
267
23.190
35.599
33.727
1.00
41.26

1DLC
1801


ATOM
1678
NH1
ARG
267
22.183
36.431
33.464
1.00
42.55

1DLC
1802


ATOM
1679
NH2
ARG 
267
22.959
34.293
33.767
1.00
44.18

1DLC
1203


ATOM
1680
N
TYR 
268
24.378
40.681
37.735
1.00
17.33

1DLC
1804


ATOM
1681
CA
TYR
268
24.711
42.098
17.748
1.00
15.33

1DLC
1805


ATOM
1682
C
TYR 
268
25.505
42.391
39.018
1.00
17.40

1DLC
1806


ATOM
1683
O
TYR 
268
26.557
43.032
38.976
1.00
20.28

1DLC
1807


ATOM
1684
CB
TYR 
268
23.432
42.932
37.739
1.00
13.81

1DLC
1808


ATOM
1685
CG
TYR 
268
23.625
44.400
38.058
1.00
15.29

1DLC
1809


ATOM
1686
CD1
TYR
268
23.588
44.852
39.378
1.00
17.01

1DLC
1810


ATOM
1687
CD2
TYR 
208
23.808
45.344
37.042
1.00
12.55

1DLC
1811


ATOM
1688
CE1
TYR 
268
23.720
46.207
39.685
1.00
18.91

1DLC
1812


ATOM
1689
CE2
TYR
268
23.937
46.703
37.335
1.00
15.35

1DLC
1813


ATOM
1690
CZ 
TYR
268
23.891
47.129
38.664
1.00
17.81

1DLC
1814


ATOM
1691
OH
TYR
268
23.989
48.470
38.983
1.00
14.63

1DLC
1815


ATOM
1692
N
ARG 
269
24.982
41.936
40.152
1.00
15.99

1DLC
1816


ATOM
1693
CA
ARG
269
25.643
42.129
41.436
1.00
16.03

1DLC
1817


ATOM
1694
C
ARG
269
27.084
41.570
41.420
1.00
20.77

1DLC
1818


ATOM
1695
O
ARG
269
28.024
42.257
41.831
1.00
23.24

1DLC
1819


ATOM
1696
CB
ARG
269
24.815
41.485
42.538
1.00
11.54

1DLC
1820


ATOM
1697
CG
ARG
269
25.506
41.407
43.864
1.00
10.15

1DLC
1821


ATOM
1698
CD
ARG
269
25.030
40.181
44.571
1.00
14.41

1DLC
1822


ATOM
1699
NE
ARG 
269
23.862
40.441
45.396
1.00
17.34

1DLC
1823


ATOM
1700
CZ
ARG 
269
22.933
39.541
45.710
1.00
21.53

1DLC
1824


ATOM
1701
NH1
ARG 
269
22.991
38.292
45.259
1.00
20.03

1DLC
1225


ATOM
1702
NH2
ARG 
269
21.977
39.878
46.558
1.00
26.32

1DLC
1826


ATOM
1703
N
ARG 
270
27.263
40.350
40.907
1.00
20.00

1DLC
1827


ATOM
1704
CA
ARG 
270
28.592
39.749
40.821
1.00
19.69

1DLC
1828


ATOM
1705
C
ARG
270
29.517
40.503
39.850
1.00
19.79

1DLC
1829


ATOM
1706
O
ARG 
270
30.647
40.841
40.199
1.00
23.48

1DLC
1830


ATOM
1707
CB
ARG
270
28.509
38.285
40.386
1.00
21.51

1DLC
1831


ATOM
1708
CC
ARC 
270
29.863
37.543
40.405
1.00
22.79

1DLC
1832


ATOM
1709
CD
ARG 
270
29.949
36.544
39.258
1.00
23.46

1DLC
1833


ATOM
1710
NE
ARC 
270
28.710
35.781
39.194
1.00
27.60

1DLC
1834


ATOM
1711
CZ
ARG 
270
28.020
35.535
38.087
1.00
23.27

1DLC
1835


ATOM
1712
NH1
ARG
270
28.437
35.961
36.906
1.00
16.76

1DLC
1036


ATOM
1713
NH2
ARG 
270
26.852
34.934
32.189
1.00
27.70

1DLC
1837


ATOM
1714
N
GLU
271
29.044
40.782
38.641
1.00
16.09

1DLC
1838


ATOM
1715
CA
GLU
271
29.871
41.489
37.672
1.00
16.33

1DLC
1839


ATOM
1716
C
GLU
271
30.236
42.910
38.103
1.00
19.12

1DLC
1840


ATOM
1717
O
GLU
271
31.364
43.351
37.878
1.00
22.66

1DLC
1841


ATOM
1718
CB
GLU
271
29.229
41.471
36.285
1.00
14.28

1DLC
1842


ATOM
1719
CG
GLU
271
29.077
40.055
35.742
1.00
18.54

1DLC
1843


ATOM
1720
CD
GLU
271
28.846
39.984
34.242
1.00
22.46

1DLC
1844


ATOM
1721
OE1
GLU
271
28.930
41.022
33.548
1.00
28.08

1DLC
1845


ATOM
1722
OE2
GLU
271
28.597
38.869
33.744
1.00
24.80

1DLC
1846


ATOM
1723
N
MET
272
29.305
43.616
38.745
1.00
17.93

1DLC
1847


ATOM
1724
CA
MET
272
29.580
44.968
39.223
1.00
15.97

1DLC
1848


ATOM
1725
C
MET
272
30.544
44.914
40.405
1.00
16.81

1DLC
1849


ATOM
1726
O
MET
272
31.253
45.876
40.684
1.00
20.74

1DLC
1850


ATOM
1727
CB
MET
272
28.300
45.705
39.616
1.00
14.65

1DLC
1851


ATOM
1728
CG
MET
272
27.362
45.953
38.464
1.00
20.31

1DLC
1852


ATOM
1729
SD
MET
272
28.183
46.581
36.973
1.00
27.85

1DLC
1853


ATOM
1730
CE
MET
272
27.795
48.276
37.085
1.00
32.60

1DLC
1854


ATOM
1731
N
THR 
273
30.571
43.769
41.104
1.00
14.53

1DLC
1855


ATOM
1732
CA
THR 
273
31.491
43.631
42.220
1.00
16.38

1DLC
1856


ATOM
1733
C
THR 
273
32.931
43.495
41.701
1.00
17.79

1DLC
1857


ATOM
1734
O
THR 
273
33.835
44.207
42.142
1.00
19.00

1DLC
1858


ATOM
1735
CS
THE 
273
31.130
42.402
43.072
1.00
12.43

1DLC
1859


ATOM
1736
OG1
THR 
273
29.875
42.532
43.716
1.00
13.76

1DLC
1860


ATOM
1737
CG2
THE 
273
32.190
42.146
44.139
1.00
12.75

1DLC
1661


ATOM
1738
N
LEO 
274
33.108
42.634
40.702
1.00
18.60

1DLC
1862


ATOM
1739
CA
LEU
274
34.413
42.376
40.100
1.00
17.81

1DLC
1863


ATOM
1740
C
LEO 
274
35.000
43.542
39.305
1.00
18.48

1DLC
1864


ATOM
1741
O
LEU 
274
36.214
43.754
39.306
1.00
23.04

1DLC
1865


ATOM
1742
CB
LEU 
274
34.340
41.136
39.198
1.00
10.87

1DLC
1866


ATOM
1743
CG
LEU 
274
33.850
39.850
39.870
1.00
11.27

10LC
1867


ATOM
1744
CD1
LEU
274
33.801
38.730
38.667
1.00
10.38

1DLC
1868


ATOM
1745
CD2
LEU
274
34.735
39.476
41.047
1.00
9.69

1DLC
1869


ATOM
1746
N
THR 
275
34.143
44.300
38.632
1.00
16.36

1DLC
1870


ATOM
1747
CA
THR
275
34.611
45.412
27.813
1.00
16.92

1DLC
1871


ATOM
1748
C
THR
275
34.489
46.807
38.413
1.00
18.24

1DLC
1872


ATOM
1749
O
THR
275
35.169
47.734
37.967
1.00
22.33

1DLC
1873


ATOM
1750
CB
THR 
275
33.932
45.417
36.421
1.00
16.38

1DLC
1874


ATOM
1751
CG1
THR 
275
32.508
45.523
36.581
1.00
22.03

1DLC
1875


ATOM
1752
CG2
THR
275
34.259
44.148
35.663
1.00
13.77

1DLC
1876


ATOM
1753
N
VAL
276
33.626
46.972
39.410
1.00
17.04

1DLC
1877


ATOM
1754
CA
VAL
276
33.443
48.287
40.021
1.00
14.32

1DLC
1878


ATOM
1755
C
VAL
276
33.739
48.366
41.523
1.00
15.28

1DLC
1879


ATOM
1756
O
VAL 
276
34.637
49.093
41.949
1.00
15.38

1DLC
1880


ATOM
1757
CR 
VAL
276
32.008
48.832
39.749
1.00
14.77

1DLC
1881


ATOM
1758
CG1
VAL 
276
31.796
50.185
40.439
1.00
14.41

1DLC
1882


ATOM
1759
CG2
VAL 
276
31.764
48.963
38.250
1.00
10.22

1DLC
1883


ATOM
1760
N
LEU
277
33.005
47.585
42.311
1.00
17.20

1DLC
1884


ATOM
1761
CA
LEU
277
33.137
47.596
43.767
1.00
16.40

1DLC
1885


ATOM
1762
C
LEU 
277
34.504
47.219
44.330
1.00
16.22

1DLC
1886


ATOM
1763
O
LEU 
277
34.967
47.831
45.294
1.00
16.50

1DLC
1887


ATOM
1764
CB
LEO 
277
32.009
46.781
44.421
1.00
13.32

1DLC
1888


ATOM
1765
CG
LEU 
277
30.565
47.184
44.067
1.00
10.97

1DLC
1889


ATOM
1766
CD1
LEU 
277
29.609
46.395
44.928
1.00
10.44

1DLC
1890


ATOM
1767
CD2
LEU
277
30.326
48.681
44.254
1.00
5.94

1DLC
1891


ATOM
1768
N
ASP
278
35.143
46.210
43.747
1.00
16.09

1DLC
1892


ATOM
1769
CA
ASP
278
36.484
45.792
44.188
1.00
17.29

1DLC
1893


ATOM
1770
C
ASP 
278
37.503
46.892
43.892
1.00
17.61

1DLC
1894


ATOM
1771
O
ASP 
278
38.430
47.134
44.659
1.00
20.19

1DLC
1895


ATOM
1772
CB
ASP
278
36.923
44.506
43.469
1.00
16.99

1DLC
1896


ATOM
1773
CG
ASP
278
36.247
43.269
44.015
1.00
15.27

1DLC
1897


ATOM
1774
OD1
ASP
278
35.693
43.336
45.127
1.00
18.92

1DLC
1898


ATOM
1775
OD2
ASP
278
36.270
42.229
43.336
1.00
18.16

1DLC
1899


ATOM
1776
N
LEU
279
37.281
47.579
42.778
1.00
20.55

1DLC
1900


ATOM
1777
CA
LEU
279
38.137
48.660
42.317
1.00
19.58

1DLC
1901


ATOM
1778
C
LEU
279
38.086
49.881
43.234
1.00
19.74

1DLC
1902


ATOM
1779
O
LEU
279
39.128
50.342
43.710
1.00
22.71

1DLC
1903


ATOM
1780
CB
LEU
279
37.734
49.052
40.893
1.00
17.72

1DLC
1904


ATOM
1781
CG
LEU
279
38.749
49.808
40.046
1.00
16.46

1DLC
1905


ATOM
1782
CD1
LEU
279
40.052
49.031
40.000
1.00
14.94

1DLC
1906


ATOM
1783
CD2
LEU
279
38.180
49.989
38.641
1.00
16.14

1DLC
1907


ATOM
1784
N
ILE
280
36.879
50.375
43.517
1.00
18.29

1DLC
1908


ATOM
1785
CA
1LE
280
36.719
51.560
44.366
1.00
13.41

1DLC
1909


ATOM
1786
C
ILE
280
37.199
51.324
45.798
1.00
13.89

1DLC
1910


ATOM
1787
O
ILE
280
37.507
52.267
46.526
1.00
13.40

1DLC
1911


ATOM
1788
CB
ILE
280
35.256
52.105
44.363
1.00
14.32

1DLC
1912


ATOM
1729
CG1
ILE
280
34.321
51.163
45.122
1.00
13.32

1DLC
1913


ATOM
1790
CG2
ILE
280
34.761
52.313
42.923
1.00
13.11

1DLC
1914


ATOM
1791
CD1
ILE
280
32.919
51.689
45.250
1.00
13.97

1DLC
1915


ATOM
1792
N
ALA
281
37.279
50.057
46.190
1.00
14.85

1DLC
1916


ATOM
1793
CA
ALA
281
37.753
49.696
47.523
1.00
14.09

1DLC
1917


ATOM
1794
C
ALA
281
39.244
50.047
47.686
1.00
16.05

1DLC
1910


ATOM
1795
O
ALA
281
39.711
50.300
48.792
1.00
19.60

1DLC
1919


ATOM
1796
CB
ALA
281
37.534
48.218
47.758
1.00
10.28

1DLC
1920


ATOM
1797
N
LEU
282
39.968
50.109
46.568
1.00
17.34

1DLC
1921


ATOM
1798
CA
LEU
282
41.404
50.412
46.566
1.00
17.85

1DLC
1922


ATOM
1799
C
LEU
282
41.772
51.901
46.551
1.00
12.73

1DLC
1923


ATOM
1800
O
LEU
282
42.853
52.282
47.002
1.00
20.35

1DLC
1924


ATOM
1801
CB
LEU
282
42.088
49.692
45.396
1.00
13.56

1DLC
1925


ATOM
1802
CC
LEU
282
41.818
48.181
45.369
1.00
15.77

1DLC
1926


ATOM
1803
CD1
LEU
282
42.557
47.527
44.222
1.00
15.69

1DLC
1927


ATOM
1804
CD2
LEU
282
42.219
47.554
46.693
1.00
11.02

1DLC
1928


ATOM
1805
N
PHE
283
40.853
52.738
46.078
1.00
17.7

1DLC
1929


ATOM
1806
CA
PHE
283
41.056
54.189
45.993
1.00
16.08

1DLC
1930


ATOM
1807
C
PHE
283
41.766
54.859
47.190
1.00
17.36

1DLC
1931


ATOM
1808
O
PHE
283
42.711
55.622
47.003
1.00
18.59

1DLC
1932


ATOM
1809
C8
PEE
283
39.714
54.910
45.750
1.00
16.79

1DLC
1933


ATOM
1810
CG
PHE
283
39.107
54.676
44.384
1.00
11.95

1DLC
1934


ATOM
1811
CD1
PEE
283
39.792
53.973
43.397
1.00
9.94

1DLC
1935


ATOM
1812
CD2
PHE
283
37.851
55.199
44.083
1.00
11.93

1DLC
1936


ATOM
1813
CE1
PEE
283
39.231
53.797
42.123
1.00
15.02

1DLC
1937


ATOM
1814
CE2
PHE
283
37.284
55.027
42.815
1.00
13.95

1DLC
1538


ATOM
1815
CZ
PHE
283
37.978
54.325
41.832
1.00
8.45

1DLC
1439


ATOM
1816
N
PRO
284
41.325
54.577
48.432
1.00
16.44

1DLC
1940


ATOM
1817
CA
PRO
284
41.954
55.188
49.613
1.00
16.04

1DLC
1941


ATOM
1818
C
PRO
284
43.435
54.855
49.775
1.00
18.64

1DLC
1942


ATOM
1819
O
PRO
284
44.206
55.624
50.357
1.00
20.90

1DLC
1943


ATOM
1820
CB
PRO
264
41.154
54.593
50.771
1.00
11.65

1DLC
1944


ATOM
1821
CG
PRO
284
39.841
54.292
50.168
1.00
13.79

1DLC
1945


ATOM
1822
CD
PRO
284
40.210
53.707
48.843
1.00
14.01

1DLC
1946


ATOM
1823
N
LEU
285
43.825
53.697
49.263
1.00
19.68

1DLC
1947


ATOM
1824
CA
LEU
285
45.198
53.244
49.366
1.00
17.84

1DLC
1948


ATOM
1825
C
LEU
285
46.126
53.959
48.383
1.00
17.73

1DLC
1949


ATOM
1826
O
LEU
285
47.334
53.743
48.391
1.00
22.07

1DLC
1950


ATOM
1827
CB
LEU
285
45.248
51.719
49.220
1.00
19.70

1DLC
1951


ATOM
1828
CO
LEU
285
44.269
50.970
50.149
1.00
20.17

1DLC
1952


ATOM
1829
CD1
LEU
285
44.337
49.484
49.897
1.00
22.11

1DLC
1953


ATOM
1830
CD2
LED
285
44.558
51.263
51.609
1.00
17.27

1DLC
1954


ATOM
1831
N
TYR
286
45.554
54.817
47.543
1.00
17.08

1DLC
1955


ATOM
1832
CA
TYR
286
46.335
55.608
46.588
1.00
16.87

1DLC
1956


ATOM
1833
C
TYR
286
46.575
56.856
47.292
1.00
17.31

1DLC
1957


ATOM
1834
O
TYR
286
47.635
57.630
46.709
1.00
18.04

1DLC
1958


ATOM
1835
CB
TYR
286
45.484
56.044
45.395
1.00
15.25

1DLC
1959


ATOM
1836
CG
TYR
266
44.982
54.917
44.529
1.00
17.75

1DLC
1960


ATOM
1837
CD
TYR
286
45.468
53.615
44.680
1.00
19.64

1DLC
1961


ATOM
1838
CD2
TYR
286
44.008
55.149
43.559
1.00
19.56

1DLC
1982


ATOM
1839
CE1
TYR
286
44.990
52.579
43.888
1.00
19.02

1DLC
1963


ATOM
1840
CE2
TYR
286
43.526
54.121
42.763
1.00
17.69

1DLC
1984


ATOM
1841
CZ
TYR
286
44.016
52.846
42.933
1.00
17.71

1DLC
1965


ATOM
1842
OH
TYR
286
43.507
51.832
42.166
1.00
19.21

1DLC
1966


ATOM
1043
N
ASP
287
46.449
57.080
48.531
1.00
15.82

1DLC
1967


ATOM
1844
CA
ASP
287
46.942
58.221
49.279
1.00
16.74

1DLC
1968


ATOM
1845
C
ASP
287
48.293
57.856
49.888
1.00
15.59

1DLC
1969


ATOM
1846
O
ASP
287
48.376
57.359
51.013
1.00
15.25

1DLC
1970


ATOM
1847
CB
ASP
207
45.958
58.648
50.365
1.00
14.24

1DLC
1971


ATOM
1848
CG
ASP
287
46.307
60.007
50.970
1.00
19.57

1DLC
1972


ATOM
1849
OD1
ASP
287
47.482
60.422
50.914
1.00
23.20

1DLC
1973


ATOM
1850
OD2
ASP
287
45.405
60.672
51.519
1.00
24.37

1DLC
1974


ATOM
1851
N
VAL
280
49.352
50.154
49.142
1.00
17.00

1DLC
1975


ATOM
1852
CA
VAL
280
50.717
57.860
49.564
1.00
19.40

1DLC
1976


ATOM
1853
C
VAL
288
51.236
58.650
50.761
1.00
20.76

1DLC
1977


ATOM
1854
O
VAL
288
52.334
58.403
51.236
1.00
24.76

1DLC
1978


ATOM
1855
CB
VAL
288
51.702
57.989
48.397
1.00
17.31

1DLC
1979


ATOM
1856
CG1
VAL
288
51.291
57.054
47.285
1.00
18.35

1DLC
1980


ATOM
1857
CG2
VAL
288
51.762
59.418
47.905
1.00
17.23

1DLC
1981


ATOM
1858
N
ARC
289
50.447
59.598
51.248
1.00
23.06

1DLC
1982


ATOM
1659
CA
ARG
289
50.846
60.391
52.410
1.00
22.35

1DLC
1983


ATOM
1060
C
ARG
289
50.361
59.717
53.669
1.00
20.93

1DLC
1984


ATOM
1861
O
ARG
289
51.051
59.715
54.684
1.00
21.28

1DLC
1985


ATOM
1862
CB
ARG
289
50.283
61.800
52.311
1.00
28.20

1DLC
1986


ATOM
1063
CG
ARG
289
50.680
62.438
51.025
1.00
31.27

1DLC
1987


ATOM
1864
CD
ARC
289
50.447
63.905
51.004
1.00
41.78

1DLC
1988


ATOM
1865
NE
ARO
289
51.389
64.454
50.046
1.00
51.47

1DLC
1989


ATOM
1066
CZ
ARG
289
52.620
64.833
50.361
1.00
52.65

1DLC
1990


ATOM
1867
NH1
ARG
289
53.034
64.743
51.621
1.00
52.33

1DLC
1991


ATOM
1868
NH2
ARG
289
53.469
65.194
49.403
1.00
53.49

1DLC
1992


ATOM
1869
N
LEU
290
49.142
59.187
53.599
1.00
21.77

1DLC
1993


ATOM
1870
CA
LEU
290
48.535
58.454
54.710
1.00
19.60

1DLC
1994


ATOM
1871
C
LEU
290
49.127
57.042
54.690
1.00
19.04

1DLC
1995


ATOM
1872
O
LEU
290
49.307
56.414
55.725
1.00
16.89

1DLC
1996


ATOM
1873
CB
LEU
290
47.014
58.368
54.545
1.00
17.72

1DLC
1997


ATOM
1874
CG
LEU
290
46.117
59.392
55.235
1.00
17.01

1DLC
1998


ATOM
1875
CD1
LEU
290
44.683
58.999
54.982
1.00
15.20

1DLC
1999


ATOM
1876
CD2
LEU
290
46.382
59.429
56.728
1.00
13.88

1DLC
2000


ATOM
1877
N
TYR
291
49.429
56.555
53.490
1.00
17.26

1DLC
2001


ATOM
1878
CA
TYR
291
50.018
55.231
53.316
1.00
17.98

1DLC
2002


ATOM
1879
C
TYR
291
51.379
55.394
52.648
1.00
19.81

1DLC
2003


ATOM
1880
O
TYR
291
51.533
55.142
51.446
1.00
19.73

1DLC
2004


ATOM
1881
CR
TYR
291
49.092
54.352
52.475
1.00
16.70

1DLC
2005


ATOM
1882
CG
TYR
291
47.755
54.103
53.142
1.00
17.30

1DLC
2006


ATOM
1883
CD1
TYR
291
47.562
53.028
54.024
1.00
15.12

1DLC
2007


ATOM
1884
CD2
TYR
291
46.674
54.963
52.927
1.00
12.11

1DLC
2000


ATOM
1885
CE1
TYR
291
46.379
52.820
54.672
1.00
15.98

1DLC
2009


ATOM
1886
CE2
TYR
291
45.469
54.763
53.576
1.00
11.41

1DLC
2010


ATOM
1007
CZ
TYR
291
45.330
53.689
54.444
1.00
13.44

1DLC
2011


ATOM
1888
OH
TYR
291
44.140
53.472
55.077
1.00
16.97

1DLC
2012


ATOM
1889
N
PRO
292
52.383
55.841
53.428
1.00
18.71

1DLC
2013


ATOM
1890
CA
PRO
292
53.760
56.078
52.988
1.00
19.79

1DLC
2014


ATOM
1891
C
PRO
292
54.569
54.810
52.769
1.00
21.30

1DLC
2015


ATOM
1892
O
PRO
292
55.746
54.877
52.441
1.00
27.34

1DLC
2016


ATOM
1893
CD
PRO
292
54.351
56.913
54.127
1.00
20.00

1DLC
2017


ATOM
1894
CG
PRO
292
53.159
57.371
54.919
1.00
24.03

1DLC
2018


ATOM
1895
CD
PRO
292
52.248
56.202
54.843
1.00
17.48

1DLC
2019


ATOM
1896
N
LYS
293
53.959
53.657
53.010
1.00
20.08

1DLC
2020


ATOM
1897
CA
LYS
293
54.625
52.381
52.793
1.00
20.58

1DLC
2021


ATOM
1898
C
LYS
293
53.692
51.508
51.950
1.00
23.91

1DLC
2022


ATOM
1899
O
LYS
293
52.543
51.884
51.690
1.00
27.52

1DLC
2023


ATOM
1900
CB
LYS
293
54.581
51.655
54.114
1.00
17.96

1DLC
2024


ATOM
1901
CG
LYS
293
55.286
52.512
55.267
1.00
20.88

1DLC
2025


ATOM
1902
CD
LYS
293
55.560
51.644
56.484
1.00
25.87

1DLC
2026


ATOM
1903
CE
LYS
293
55.546
52.459
57.770
1.00
34.09

1DLC
2027


ATOM
1904
NZ
LYS
293
56.452
53.641
57.721
1.00
38.99

1DLC
2028


ATOM
1905
N
GLU
294
54.180
50.345
51.530
1.00
22.97

1DLC
2029


ATOM
1906
CA
GLU
294
53.359
49.411
50.772
1.00
20.92

1DLC
2030


ATOM
1907
C
GLU
294
52.267
48.916
51.722
1.00
20.22

1DLC
2031


ATOM
1908
G
GLU
294
52.471
48.835
52.938
1.00
19.74

1DLC
2032


ATOM
1909
CB
GLU
294
54.192
48.218
50.314
1.00
24.35

1DLC
2033


ATOM
1910
CG
GLU
294
55.435
48.586
49.521
1.00
36.21

1DLC
2034


ATOM
1911
CD
GLU
294
56.236
47.367
49.086
1.00
37.88

1DLC
2035


ATOM
.1912
OE1
GLU
294
56.648
46.574
49.966
1.00
43.62

1DLC
2036


ATOM
1913
OE2
GLU
294
56.450
47.207
47.864
1.00
40.00

1DLC
2037


ATOM
1914
N
VAL
295
51.101
48.607
51.177
1.00
21.65

1DLC
2038


ATOM
1915
CA
VAL
295
49.999
48.127
52.002
1.00
21.78

1DLC
2039


ATOM
1916
C
VAL
295
49.628
46.669
51.752
1.00
20.58

1DLC
2040


ATOM
1917
O
VAL
295
49.519
46.236
50.608
1.00
21.08

1DLC
2041


ATOM
1918
CB
VAL
295
48.732
48.989
51.809
1.00
20.64

1DLC
2042


ATOM
1919
CG
VAL
295
47.553
48.390
52.569
1.00
22.03

1DLC
2043


ATOM
1920
CG2
VAL
295
48.991
50.400
52.284
1.00
22.52

1DLC
2044


ATOM
1921
N
LYS
296
49.509
45.905
52.834
1.00
18.88

1DLC
2045


ATOM
1922
CA
LYS
296
49.082
44.516
52.754
1.00
17.81

1DLC
2046


ATOM
1923
C
LYS
296
47.586
44.560
53.085
1.00
20.39

1DLC
2047


ATOM
1924
O
LYS
296
47.195
45.013
54.172
1.00
20.26

1DLC
2048


ATOM
1925
CB
LYS
296
49.809
43.651
53.782
1.00
15.08

1DLC
2049


ATOM
1925
CG
LYS
296
49.313
42.216
53.816
1.00
12.45

1DLC
2050


ATOM
1927
CD
LYS
296
49.980
41.4285
4.928
1.00
16.65

1DLC
2051


ATOM
1928
CE
LYS
296
49.434
40.008
55.028
1.00
12.92

1DLC
2052


ATOM
1929
NZ
LYS
296
48.362
39.892
56.047
1.00
15.35

1DLC
2053


ATOM
1930
N
THR
297
46.747
44.166
52.135
1.00
20.26

1DLC
2054


ATOM
1931
CA
THR
297
45.309
44.186
52.373
1.00
19.90

1DLC
2055


ATOM
1932
C
THR
297
44.572
43.049
51.671
1.00
19.99

1DLC
2056


ATOM
1933
O
THR
297
45.177
42.286
50.923
1.00
24.16

1DLC
2057


ATOM
1934
CB
THR
297
44.701
45.550
51.980
1.00
17.52

1DLC
2058


ATOM
1935
CG1
THR
297
43.325
45.579
52.366
1.00
18.25

1DLC
2059


ATOM
1936
CG2
THR
297
44.829
45.799
50.476
1.00
14.77

1DLC
2060


ATOM
1937
N
GLU
298
43.270
42.935
51.913
1.00
20.33

1DLC
2061


ATOM
1938
CA
GLU
298
42.461
41.874
51.307
1.00
19.29

1DLC
2062


ATOM
1939
C
GLU
298
40.997
42.259
51.105
1.00
17.75

1DLC
2063


ATOM
1940
O
GLU
298
40.470
43.129
51.795
1.00
20.54

1DLC
2064


ATOM
1941
CB
GLU
298
42.536
40.605
52.166
1.00
14.48

1DLC
2065


ATOM
1942
CG
GLU
298
42.130
40.827
53.611
1.00
14.45

1DLC
2066


ATOM
1943
CD
GLU
298
42.441
39.644
54.506
1.00
15.68

1DLC
2067


ATOM
1944
OE1
GLU
298
43.588
39.157
54.490
1.00
22.29

1DLC
2068


ATOM
1945
OE2
GLU
298
41.544
39.211
55.247
1.00
19.26

1DLC
2059


ATOM
1946
N
LEU
299
40.349
41.596
50.156
1.00
17.55

1DLC
2070


ATOM
1947
CA
LEU
299
38.933
41.826
49.856
1.00
18.90

1DLC
2071


ATOM
1948
C
LEU
299
38.165
40.652
50.488
1.00
21.39

1DLC
2072


ATOM
1949
O
LEU
299
38.385
39.493
50.108
1.00
23.60

1DLC
2073


ATOM
1950
CB
LEU
299
38.717
41.862
48.338
1.00
13.32

1DLC
2074


ATOM
1951
CG
LEU
299
39.472
42.945
47.563
1.00
10.97

1DLC
2075


ATOM
1952
CD3
LEU
299
39.359
42.688
46.085
1.00
14.82

1DLC
2076


ATOM
1953
CD2
LEU
299
38.929
44.312
47.894
1.00
9.97

1DLC
2077


ATOM
1954
N
THR
300
37.291
40.943
51.455
1.00
19.12

1DLC
2078


ATOM
1955
CA
THR
300
36.539
39.902
52.163
1.00
17.44

1DLC
2079


ATOM
1956
C
THR
300
35.105
39.598
51.710
1.00
20.09

1DLC
2080


ATOM
1957
O
THR
300
34.439
38.743
52.297
1.00
21.20

1DLC
2081


ATOM
1958
CB
THR
300
36.492
40.200
53.680
1.00
18.14

1DLC
2082


ATOM
1959
CG1
THR
300
35.829
41.449
53.904
1.00
20.85

1DLC
2083


ATOM
1960
CG2
THR
300
37.899
40.264
54.270
1.00
17.00

1DLC
2084


ATOM
1961
N
ARG
301
34.631
40.268
50.667
1.00
20.53

1DLC
2085


ATOM
1962
CA
ARG
301
33.259
40.074
50.184
1.00
18.35

1DLC
2086


ATOM
1963
C
ARG
301
32.953
38.762
49.451
1.00
19.18

1DLC
2087


ATOM
1964
O
ARG
301
33.850
38.158
48.849
1.00
18.71

1DLC
2088


ATOM
1965
CB
ARG
301
32.842
41.248
49.291
1.00
13.09

1DLC
2089


ATOM
1966
CG
ARG
301
33.280
41.126
47.830
1.00
13.61

1DLC
2090


ATOM
1967
CD
ARG
301
34.792
41.044
47.678
1.00
14.65

1DLC
2091


ATOM
1368
NE
ARG
301
35.197
40.844
46.291
1.00
14.20

1DLC
2092


ATOM
1969
CZ
ARG
301
35.305
39.661
45.890
1.00
17.27

1DLC
2093


ATOM
1970
NH1
ARG
301
35.040
38.534
46.343
1.00
13.79

1DLC
2094


ATOM
1971
NH2
ARG
301
35.667
39.613
44.420
1.00
14.12

1DLC
2095


ATOM
1972
N
ASP
302
31.690
38.370
49.478
1.00
19.99

1DLC
2096


ATOM
1973
CA
ASP
302
31.196
37.161
48.817
1.00
20.22

1DLC
2097


ATOM
1974
C
ASP
302
30.662
37.483
47.432
1.00
20.75

1DLC
2098


ATOM
1975
O
ASP
302
30.141
38.573
47.196
1.00
24.04

1DLC
2099


ATOM
1976
CB
ASP
302
29.980
36.582
49.556
1.00
24.46

1DLC
2100


ATOM
1977
CG
ASP
302
30.316
35.978
50.886
1.00
31.05

1DLC
2101


ATOM
1978
OG1
ASP
302
31.510
35.740
51.162
1.00
41.38

1DLC
2102


ATOM
1979
OD2
ASP
302
29.363
35.721
51.657
1.00
34.73

1DLC
2103


ATOM
1980
N
VAL
303
30.741
36.501
46.544
1.00
18.31

1DLC
2104


ATOM
1981
CA
VAL
303
30.182
36.601
45.199
1.00
18.50

1DLC
2105


ATOM
1982
C
VAL
303
29.592
35.219
44.926
1.00
17.19

1DLC
2106


ATOM
1983
O
VAL
303
30.131
34.204
45.370
1.00
18.03

1DLC
2107


ATOM
1984
CB
VAL
303
31.204
37.008
44.094
1.00
19.37

1DLC
2108


ATOM
1985
CG1
VAL
303
31.744
38.402
44.369
1.00
21.25

1DLC
2109


ATOM
1986
CG2
VAL
303
32.328
35.992
43.973
1.00
21.50

1DLC
2110


ATOM
1987
N
LEO
304
28.410
35.201
44.330
1.00
16.94

1DLC
2111


ATOM
1988
CA
LEU
304
27.713
33.962
44.022
1.00
13.97

1DLC
2112


ATOM
1989
C
LEU
304
27.764
33.726
42.527
1.00
14.14

1DLC
2113


ATOM
1990
O
LEO
304
27.474
34.622
41.730
1.00
13.74

1DLC
2114


ATOM
1991
CB
LEO
304
26.235
34.053
44.433
1.00
14.18

1DLC
2115


ATOM
1992
CO
LED
304
25.680
34.294
45.846
1.00
13.89

1DLC
2116


ATOM
1993
CD1
LEU
304
25.252
32.993
46.457
1.00
14.90

1DLC
2117


ATOM
1994
CD2
LEU
304
26.641
35.052
46.745
1.00
11.27

1DLC
2118


ATOM
1995
N
THR
305
28.146
32.521
42.140
1.00
14.38

1DLC
2119


ATOM
1996
CA
THR
305
28.175
32.187
40.721
1.00
16.18

1DLC
2120


ATOM
1997
C
THR
305
26.737
31.864
40.282
1.00
17.39

1DLC
2121


ATOM
1998
O
THR
305
25.845
31.688
41.124
1.00
15.94

1DLC
2122


ATOM
1999
CD
THR
305
29.115
30.969
40.422
1.00
17.34

1DLC
2123


ATOM
2000
OG1
THR
305
29.021
30.000
41.475
1.00
19.98

1DLC
2124


ATOM
2001
CG2
THR
305
30.565
31.415
40.270
1.00
18.26

1DLC
2125


ATOM
2002
N
ASP
306
26.488
31.891
38.978
1.00
15.04

1DLC
212G


ATOM
2003
CA
ASP
306
25.177
31.551
38.437
1.00
17.79

1DLC
2127


ATOM
2004
C
ASP
306
24.785
30.157
38.913
1.00
21.19

1DLC
2128


ATOM
2005
O
ASP
306
25.651
29.278
39.067
1.00
24.55

1DLC
2129


ATOM
2006
C8
ASP
306
25.222
31.530
36.912
1.00
15.07

1DLC
2130


ATOM
2007
CG
ASP
306
25.286
32.905
36.310
1.00
15.88

1DLC
2111


ATOM
2008
OD1
ASP
306
24.822
33.867
36.946
1.00
18.05

1DLC
2132


ATOM
2009
OD2
ASP
306
25.777
33.024
35.174
1.00
23.36

1DLC
2133


ATOM
2010
N
PRO
307
23.483
29.938
39.179
1.00
22.83

1DLC
2134


ATOM
2011
CA
PRO
307
23.004
28.623
39.639
1.00
20.21

1DLC
2135


ATOM
2012
C
PRO
307
23.289
27.551
38.587
1.00
16.74

1DLC
2136


ATOM
2013
O
PRO
307
23.289
27.827
37.389
1.00
17.78

1DLC
2137


ATOM
2014
CB
PRO
307
21.502
28.848
39.811
1.00
20.31

1DLC
2138


ATOM
2015
CG
PRO
307
21.410
30.306
40.150
1.00
21.80

1DLC
2139


ATOM
2016
CD
PRO
307
22.388
30.925
39.175
1.00
20.89

1DLC
2140


ATOM
2017
N
ILE
308
23.547
26.333
39.033
1.00
18.04

1DLC
2141


ATOM
2018
CA
ILE
308
23.851
25.245
38.107
1.00
19.10

1DLC
2142


ATOM
2019
C
ILE
308
22.579
24.514
37.684
1.00
21.11

1DLC
2143


ATOM
2020
O
ILE
308
22.004
23.759
36.473
1.00
23.40

1DLC
2144


ATOM
2021
CS
ILE
308
24.833
24.227
36.753
1.00
20.63

1DLC
2145


ATOM
2022
CG1
ILE
308
25.992
24.971
39.439
1.00
21.46

1DLC
2146


ATOM
2023
CG2
ILE
308
25.352
23.252
37.700
1.00
19.02

1DLC
2147


ATOM
2024
CD1
ILE
308
26.923
24.082
40.247
1.00
17.99

1DLC
2148


ATOM
2025
N
VAL
309
22.119
24.763
36.460
1.00
23.15

1DLC
2149


ATOM
2026
CA
VAL
309
20.907
24.106
35.944
1.00
25.59

1DLC
2150


ATOM
2027
C
VAL
309
21.139
23.415
34.602
1.00
25.03

1DLC
2151


ATOM
2028
O
VAL
309
21.908
23.891
33.778
1.00
24.20

1DLC
2152


ATOM
2029
CB
VAL
309
19.689
25.093
35.808
1.00
23.31

1DLC
2153


ATOM
2030
CG1
VAL
309
19.295
25.652
37.160
1.00
24.72

1DLC
2154


ATOM
2031
CG2
VAL
309
20.005
26.214
34.847
1.00
25.99

1DLC
2155


ATOM
2032
N
GLY
310
20.462
22.290
34.393
1.00
26.11

1DLC
2156


ATOM
2033
CA
GLY
310
20.610
21.549
33.151
1.00
28.39

1DLC
2157


ATOM
2034
C
GLY
310
19.889
22.100
31.926
1.00
31.24

1DLC
2152


ATOM
2035
O
GLY
310
20.257
21.777
30.802
1.00
35.55

1DLC
2159


ATOM
2036
N
VAL
311
18.266
22.927
32.128
1.00
32.38

1DLC
2160


ATOM
2037
CA
VAL
311
18.102
23.498
31.012
1.00
30.87

1DLC
2161


ATOM
2038
C
VAL
311
18.111
25.024
31.015
1.00
29.77

1DLC
2162


ATOM
2039
O
VAL
311
18.175
25.648
32.070
1.00
31.01

1DLC
2163


ATOM
2040
CB
VAL
311
16.616
23.022
31.028
1.00
31.20

1DLC
2164


ATOM
2041
CG1
VAL
311
16.525
21.524
30.803
1.00
32.24

1DLC
2165


ATOM
2042
CG2
VAL
311
15.966
23.374
12.347
1.00
28.27

1DLC
2166


ATOM
2043
N
ASN
312
17.976
25.613
29.832
1.00
34.45

1DLC
2167


ATOM
2044
CA
ASN
312
17.968
27.071
29.683
1.00
38.67

1DLC
2168


ATOM
2045
C
ASN
312
16.678
27.741
30.145
1.00
37.69

1DLC
2169


ATOM
2046
O
ASN
312
16.696
28.874
30.619
1.00
39.59

1DLC
2170


ATOM
2047
CM
ASN
312
18.219
27.462
28.225
1.00
46.17

1DLC
2171


ATOM
2048
CG
ASN
312
19.670
27.287
27.806
1.00
53.31

1DLC
2172


ATOM
2049
OD1
ASN
312
20.581
27.275
28.638
1.00
56.28

1DLC
2173


ATOM
2050
ND2
ASN
312
19.894
27.181
26.500
1.00
59.74

1DLC
2174


ATOM
2051
N
ASN
313
15.559
27.048
29.963
1.00
35.04

1DLC
2175


ATOM
2052
CA
ASN
313
14.243
27.559
30.339
1.00
31.97

1DLC
2176


ATOM
2053
C
ASN
313
13.538
26.549
31.247
1.00
30.91

1DLC
2177


ATOM
2054
O
ASN
313
13.221
25.432
30.819
1.00
32.94

1DLC
2178


ATOM
2055
CB
ASN
313
13.427
27.807
29.065
1.00
31.98

1DLC
2179


ATOM
2056
CG
ASN
313
12.051
28.364
29.339
1.00
29.11

1DLC
2180


ATOM
2057
OD1
ASN
313
11.646
22.542
30.486
1.00
31.35

1DLC
2181


ATOM
2058
ND2
ASN
313
11.322
28.651
28.279
1.00
26.80

1DLC
2182


ATOM
2059
N
LEU
314
13.295
26.950
32.493
1.00
26.72

1DLC
2123


ATOM
2060
CA
LEU
314
12.648
26.091
33.486
1.00
24.82

1DLC
2184


ATOM
2061
C
LEU
314
11.114
26.096
33.478
1.00
26.88

1DLC
2185


ATOM
2062
O
LEU
314
10.483
25.503
34.363
1.00
29.59

1DLC
2186


ATOM
2063
CS 
LEU
314
13.151
26.432
34.291
1.00
21.60

1DLC
2187


ATOM
2064
CG
LEU
314
14.519
25.889
35.295
1.00
22.09

1DLC
2188


ATOM
2065
CD1
LEU
314
14.849
26.325
36.707
1.00
20.63

1DLC
2189


ATOM
2066
CD2
LEU
314
14.510
24.373
35.217
1.00
20.55

1DLC
2190


ATOM
2067
N
ARG
315
10.525
26.768
32.491
1.00
24.99

1DLC
2191


ATOM
2068
CA
ARG
315
9.072
26.865
32.353
1.00
24.53

1DLC
2192


ATOM
2069
C
ARG
315
8.306
27.125
33.659
1.00
21.66

1DLC
2193


ATOM
2070
O
ARG
315
7.305
26.478
33.947
1.00
25.12

1DLC
2194


ATOM
2071
CB
ARG
315
8.508
25.640
31.619
1.00
28.28

1DLC
2195


ATOM
2072
CG
ARG
315
8.737
25.652
30.105
1.00
34.47

1DLC
2196


ATOM
2073
CD
ARG
315
7.977
24.524
29.387
1.00
45.54

1DLC
2197


ATOM
2074
NE 
ARG
315
6.513
24.685
29.412
1.00
59.49

1DLC
2198


ATOM
2075
CZ 
ARG
315
5.682
24.048
30.246
1.00
63.23

1DLC
2199


ATOM
2076
NH1
ARG
315
6.149
23.191
31.149
1.00
65.85

1DLC
2200


ATOM
2077
NH2
ARG
315
4.373
24.264
30.179
1.00
62.27

1DLC
2201


ATOM
2078
N
GLY
316
8.807
28.060
34.458
1.00
21.30

1DLC
2202


ATOM
2079
CA
GLY
316
8.151
28.420
35.704
1.00
16.98

1DLC
2203


ATOM
2080
C
GLY
316
8.497
27.638
36.953
1.00
18.35

1DLC
2204


ATOM
2081
O
GLY
316
8.082
28.010
38.049
1.00
17.47

1DLC
2205


ATOM
2082
N
TYR
317
9.256
26.561
36.812
1.00
20.77

1DLC
2206


ATOM
2083
CA
TYR
317
9.615
25.751
37.971
1.00
20.18

1DLC
2207


ATOM
2084
C
TYR
317
10.805
26.243
38.782
1.00
21.76

1DLC
2208


ATOM
2085
O
TYR
317
11.103
25.704
39.847
1.00
24.15

1DLC
2209


ATOM
2086
CB
TYR
317
9.800
24.298
37.554
1.00
22.53

1DLC
2210


ATOM
2087
CG
TYR
317
8.497
23.648
37.192
1.00
23.66

1DLC
2211


ATOM
2088
CD1
TYR
317
7.703
23.062
38.171
1.00
25.39

1DLC
2212


ATOM
2089
CD2
TYR
317
8.027
23.668
35.882
1.00
24.11

1DLC
2213


ATOM
2090
CE1
TYR
117
6.469
22.512
37.860
1.00
27.42

1DLC
2214


ATOM
2091
CE2
TYR
317
6.795
23.127
35.557
1.00
27.40

1DLC
2215


ATOM
2092
CZ
TYR
317
6.018
22.551
36.557
1.00
29.75

1DLC
2216


ATOM
2093
OH 
TYR
317
4.782
22.026
36.262
1.00
34.32

1DLC
2217


ATOM
2094
N
GLY
318
11.475
27.281
38.300
1.00
20.77

1DLC
2218


ATOM
2095
CA
GLY
318
12.608
27.810
39.029
1.00
18.55

1DLC
2219


ATOM
2096
C
GLY
318
12.210
28.393
40.374
1.00
19.44

1DLC
2220


ATOM
2097
O
GLY
318
11.130
28.977
40.519
1.00
20.54

1DLC
2221


ATOM
2098
N
THR
319
13.069
28.209
41.369
1.00
17.62

1DLC
2222


ATOM
2099
CA
THR
319
12.834
28.739
42.712
1.00
17.45

1DLC
2223


ATOM
2100
C
THR
119
12.556
30.236
42.630
1.00
20.62

1DLC
2224


ATOM
2101
O
THR
319
13.184
30.941
41.842
1.00
25.06

1DLC
2225


ATOM
2102
CH 
THR
319
14.075
28.548
43.573
1.00
17.42

1DLC
2226


ATOM
2103
CG1
THR
319
14.492
27.180
43.496
1.00
21.15

1DLC
2227


ATOM
2104
CG2
THR
319
13.794
28.924
45.012
1.00
14.83

1DLC
2228


ATOM
2105
N
THR
320
11.631
30.732
43.440
1.00
19.91

1DLC
2229


ATOM
2106
CA
THR
320
11.307
32.157
43.398
1.00
18.68

1DLC
2230


ATOM
2107
C
THR
320
12.414
33.064
43.936
1.00
20.02

1DLC
2221


ATOM
2108
O
THR
320
13.210
32.666
44.790
1.00
24.12

1DLC
2232


ATOM
2109
CR 
THR
320
9.997
32.468
44.141
1.00
16.01

1DLC
2233


ATOM
2110
CG1
THE
320
10.095
32.022
45.493
1.00
19.03

1DLC
2234


ATOM
2111
CG2
THE
320
8.848
31.775
43.477
1.00
10.83

1DLC
2235


ATOM
2112
N
PHE
321
12.446
34.291
43.431
1.00
18.76

1DLC
2236


ATOM
2113
CA
PHE
321
13.430
35.292
43.835
1.00
18.42

1DLC
2237


ATOM
2114
C
PHE
321
13.600
35.328
45.359
1.00
19.97

1DLC
2238


ATOM
2115
O
PHE
321
14.700
35.142
45.882
1.00
18.92

1DLC
2239


ATOM
2116
CB
PHE
321
12.990
36.666
43.311
1.00
18.89

1DLC
2240


ATOM
2117
CG
PHE
321
14.009
37.758
43.500
1.00
20.25

1DLC
2241


ATOM
2118
CD1
PHE
321
14.366
38.199
44.776
1.00
19.19

1DLC
2242


ATOM
2119
CD2
PHE
321
14.589
38.373
42.398
1.00
18.51

1DLC
2241


ATOM
2120
CE1
PHE
321
15.279
39.235
44.947
1.00
20.39

1DLC
2244


ATOM
2121
CE2
PHE
321
15.504
39.412
42.560
1.00
19.17

1DLC
2245


ATOM
2122
CZ 
PHE
321
15.849
39.844
43.835
1.00
21.01

1DLC
2246


ATOM
2123
N
SER
322
12.497
35.528
46.069
1.00
21.66

1DLC
2247


ATOM
2124
CA
SER
322
12.527
35.587
47.531
1.00
23.88

1DLC
2248


ATOM
2125
C
SER
322
12.978
34.310
48.220
1.00
21.84

1DLC
2249


ATOM
2126
O
SER
322
13.594
34.361
49.283
1.00
23.06

1DLC
2250


ATOM
2127
CB
SER
322
11.176
36.030
48.079
1.00
24.50

1DLC
2251


ATOM
2128
OG 
SER
322
10.894
37.344
47.621
1.00
37.62

1DLC
2252


ATOM
2129
N
ASN
323
12.695
33.163
47.614
1.00
22.20

1DLC
2253


ATOM
2130
CA
ASN
323
13.117
31.900
48.208
1.00
23.04

1DLC
2254


ATOM
2131
C
ASN
323
14.606
31.623
48.007
1.00
21.38

1DLC
2255


ATOM
2132
O
ASN
323
15.159
30.688
48.582
1.00
22.81

1DLC
2256


ATOM
2133
CR
ASN
323
12.250
30.743
47.732
1.00
24.92

1DLC
2257


ATOM
2134
CG
ASN
323
10.897
30.730
48.408
1.00
25.16

1DLC
2258


ATOM
2135
OD1
ASN 
323
10.741
31.216
49.525
1.00
26.34

1DLC
2259


ATOM
2136
NO2
ASN
323
9.909
30.193
47.727
1.00
29.75

1DLC
2260


ATOM
2137
N
ILE
324
15.240
32.426
47.160
1.00
19.13

1DLC
2261


ATOM
2138
CA
ILE
324
16.672
32.318
46.961
1.00
17.26

1DLC
2262


ATOM
2139
C
ILE
324
17.340
33.454
47.759
1.00
18.23

1DLC
2263


ATOM
2140
O
ILE
324
18.050
33.214
48.742
1.00
18.12

1DLC
2264


ATOM
2141
CB
ILE
324
17.073
32.449
45.485
1.00
13.05

1DLC
2265


ATOM
2142
CG1
ILE
324
16.380
31.379
44.655
1.00
10.69

1DLC
2266


ATOM
2143
CG2
ILE
324
18.584
32.294
45.342
1.00
13.12

1DLC
2267


ATOM
2144
CD1
TIM
324
16.771
31.402
43.202
1.00
11.56

1DLC
2268


ATOM
2145
N
GLU
325
17.014
34.693
47.399
1.00
17.70

1DLC
2269


ATOM
2146
CA
GLU
325
17.608
35.866
48.038
1.00
19.04

1DLC
2270


ATOM
2147
C
GLU
325
17.473
35.948
49.560
1.00
21.70

1DLC
2271


ATOM
2148
O
GLU
325
18.416
36.347
50.242
1.00
23.28

1DLC
2272


ATOM
2149
CG
GLU
325
17.117
37.149
47.356
1.00
20.14

1DLC
2273


ATOM
2150
CG
GLU
325
17.856
38.439
47.749
1.00
19.56

1DLC
2274


ATOM
2151
CD
GLU
325
19.369
38.422
47.477
1.00
19.74

1DLC
2275


ATOM
2152
OE1
GLU
325
19.836
37.805
46.497
1.00
19.17

1DLC
2276


ATOM
2153
OE2
GLU
325
20.104
39.056
48.259
1.00
21.56

1DLC
2277


ATOM
2154
N
ASN
326
16.333
35.529
50.100
1.00
22.82

1DLC
2278


ATOM
2155
CA
ANN
326
16.133
35.568
51.546
1.00
21.61

1DLC
2279


ATOM
2156
C
ASN
326
16.849
34.441
52.271
1.00
22.46

1DLC
2280


ATOM
2157
O
ASN
326
16.948
34.449
53.499
1.00
22.03

1DLC
2281


ATOM
2158
C8
ASN
326
14.646
35.512
51.891
1.00
25.83

1DLC
2282


ATOM
2159
CG
ASN
326
13.912
36.795
51.551
1.00
30.73

1DLC
2263


ATOM
2160
OD1
ASN
326
12.713
36.784
51.296
1.00
36.78

1DLC
2264


ATOM
2161
NID2
ASN
326
14.621
37.907
51.556
1.00
33.22

1DLC
2265


ATOM
2162
N
TYR
327
17.346
33.469
51.515
1.00
21.89

1DLC
2286


ATOM
2163
CA
TYR
327
18.023
32.335
52.128
1.00
23.83

1DLC
2267


ATOM
2164
C
TYR
327
19.516
32.203
51.912
1.00
22.96

1DLC
2288


ATOM
2165
O
TYR
327
20.148
31.355
52.533
1.00
27.36

1DLC
2289


ATOM
2166
CB
TYR
327
17.313
31.034
51.773
1.00
30.00

1DLC
2290


ATOM
2167
CG
TYR
327
15.943
30.955
52.399
1.00
33.84

1DLC
2291


ATOM
2168
CD1
TYR
327
14.835
31.495
51.755
1.00
32.53

1DLC
2292


ATOM
2169
CD2
TYR
327
15.761
30.363
53.649
1.00
34.52

1DLC
2293


ATOM
2170
CE1
TYR
327
13.589
31.452
52.333
1.00
36.59

1DLC
2294


ATOM
2171
CE2
TYR
327
14.511
30.313
54.239
1.00
36.84

1DLC
2295


ATOM
2172
CE
TYR
327
13.427
30.859
53.574
1.00
39.48

1DLC
2296


ATOM
2173
OH
TYR
327
12.167
30.805
54.138
1.00
48.47

1DLC
2297


ATOM
2174
N
ILE
328
20.085
33.005
51.020
1.00
20.63

1DLC
2298


ATOM
2175
CA
ILE
328
21.525
32.955
50.813
1.00
19.45

1DLC
2299


ATOM
2176
C
ILE
328
22.176
33.473
52.102
1.00
23.48

1DLC
2300


ATOM
2177
O
ILE
328
21.511
34.124
52.919
1.00
24.83

1DLC
2301


ATOM
2178
CS
ILE
328
21.977
33.815
49.610
1.00
17.68

1DLC
2302


ATOM
2179
CG1
ILE
328
21.666
35.292
49.842
1.00
19.52

1DLC
2303


ATOM
2180
CG2
ILE
328
21.308
33.332
48.348
1.00
15.95

1DLC
2304


ATOM
2181
CD1
ILE
328
22.220
36.207
48.778
1.00
18.88

1DLC
2305


ATOM
2182
N
ARG
329
23.457
33.161
52.296
1.00
24.61

1DLC
2306


ATOM
2183
CA
ARG
329
24.207
33.576
53.486
1.00
21.84

1DLC
2307


ATOM
2184
C
ARG
329
24.091
35.065
53.820
1.00
22.27

1DLC
2308


ATOM
2185
O
ARG
329
24.268
35.917
52.953
1.00
25.04

1DLC
2309


ATOM
2186
CB
ARG
329
25.683
33.242
53.299
1.00
23.15

1DLC
2310


ATOM
2187
CG
ARG
329
25.990
31.776
53.243
1.00
24.82

1DLC
2311


ATOM
2188
CD
ARG
329
26.732
31.373
54.501
1.00
28.71

1DLC
2312


ATOM
2189
NE
ARG
329
28.173
31.390
54.297
1.00
24.15

1DLC
2313


ATOM
2190
CZ
ARG
329
29.077
31.204
55.256
1.00
23.69

1DLC
2314


ATOM
2191
NH1
ARC
329
28.710
30.996
56.515
1.00
13.74

1DLC
2315


ATOM
2192
NH2
ARG
329
30.360
31.179
54.937
1.00
20.55

1DLC
2316


ATOM
2193
N
LYS
330
23.804
35.373
55.080
1.00
24.03

1DLC
2317


ATOM
2194
CA
LYS
330
23.696
36.763
55.533
1.00
24.69

1DLC
2316


ATOM
2195
C
LYS
330
25.041
37.243
56.085
1.00
22.84

1DLC
2319


ATOM
2196
O
LYS
330
25.929
36.428
56.345
1.00
22.64

1DLC
2320


ATOM
2197
CB
LYS
330
22.608
36.896
56.605
1.00
27.12

1DLC
2321


ATOM
2198
CG
LYS
330
21.199
36.885
56.033
1.00
33.76

1DLC
2322


ATOM
2199
CD
LYS
330
20.164
37.200
57.096
1.00
42.42

1DLC
2323


ATOM
2200
CE
LYS
330
16.753
37.179
56.510
1.00
47.90

1DLC
2324


ATOM
2201
NZ
LYS
330
18.405
35.828
55.959
1.00
53.46

1DLC
2325


ATOM
2202
N
PRO
331
25.219
38.568
56.245
1.00
22.24

1DLC
2326


ATOM
2203
CA
PRO
331
26.479
39.105
56.771
1.00
20.54

1DLC
2327


ATOM
2204
C
PRO
331
27.000
38.248
57.913
1.00
21.52

1DLC
2328


ATOM
2205
O
PRO
331
26.327
38.053
58.918
1.00
23.22

1DLC
2329


ATOM
2206
CS
PRO
331
26.079
40.497
57.230
1.00
21.52

1DLC
2330


ATOM
2207
CG
PRO
331
25.100
40.898
55.163
1.00
19.00

1DLC
2331


ATOM
2208
CD
PRO
331
24.252
39.654
55.996
1.00
19.95

1DLC
2332


ATOM
2209
N
HIS
332
28.193
37.700
57.715
1.00
21.33

1DLC
2333


ATOM
2210
CA
HIS
332
28.810
36.810
58.682
1.00
18.59

1DLC
2334


ATOM
2211
C
HIS
332
30.310
37.019
58.847
1.00
19.87

1DLC
2335


ATOM
2212
O
HIS
332
30.991
37.511
57.949
1.00
19.56

1DLC
2336


ATOM
2213
CB
HIS
332
26.597
35.371
58.214
1.00
14.92

1DLC
2337


ATOM
2214
CG
HIS
332
29.196
35.084
56.870
1.00
13.36

1DLC
2338


ATOM
2215
ND1
HIS
332
30.474
34.589
56.712
1.00
17.22

1DLC
2339


ATOM
2216
CD2
HIS
332
28.700
35.242
55.619
1.00
13.52

1DLC
2340


ATOM
2217
CE1
HIS
332
30.741
34.454
55.425
1.00
16.38

1DLC
2341


ATOM
2218
NE2
HIS
332
29.680
34.843
54.740
1.00
18.37

1DLC
2342


ATOM
2219
N
LED
333
30.828
36.585
59.987
1.00
20.07

1DLC
2343


ATOM
2220
CA
LEU
333
32.260
36.643
60.259
1.00
17.84

1DLC
2344


ATOM
2221
C
LED
333
32.683
35.741
99.780
1.00
18.07

1DLC
2345


ATOM
2222
O
LEU
333
32.246
34.784
58.719
1.00
19.71

1DLC
2346


ATOM
2223
CB
LEU
333
32.518
36.070
61.651
1.00
12.65

1DLC
2347


ATOM
2224
CG
LEU
333
33.158
36.944
62.721
1.00
14.26

1DLC
2348


ATOM
2225
CD1
LED
333
32.855
38.403
62.506
1.00
13.22

1DLC
2349


ATOM
2226
CD2
LED
333
32.689
36.472
64.083
1.00
9.06

1DLC
2350


ATOM
2227
N
PHE
334
34.089
36.065
58.738
1.00
16.81

1DLC
2351


ATOM
2228
CA
PHE
334
34.756
35.294
57.689
1.00
16.45

1DLC
2352


ATOM
2229
C
PHE
334
35.055
33.841
58.074
1.00
18.71

1DLC
2353


ATOM
2230
O
PHE
334
35.438
33.562
59.217
1.00
21.26

1DLC
2354


ATOM
2231
CS 
PHE
334
36.053
35.994
57.257
1.00
16.25

1DLC
2355


ATOM
2232
CG
PHE
334
36.519
35.602
55.891
1.00
15.09

1DLC
2356


ATOM
2233
CD1
PRE
334
37.286
14.455
55.702
1.00
13.90

1DLC
2357


ATOM
2234
CD2
PHE
334
36.141
36.350
54.779
1.00
13.34

1DLC
2358


ATOM
2235
CE1
PHE
334
37.663
34.056
54.422
1.00
11.52

1DLC
2359


ATOM
2236
CE2
PHE
334
36.516
35.958
53.496
1.00
14.32

1DLC
2360


ATOM
2237
CZ
PHE
334
37.278
34.806
53.318
1.00
12.48

1DLC
2361


ATOM
2238
N
ASP
335
34.851
32.919
57.133
1.00
14.83

1DLC
2362


ATOM
2239
CA
ASP
335
35.125
31.501
57.382
1.00
15.09

1DLC
2363


ATOM
2240
C
ASP
335
35.576
30.773
56.119
1.00
15.60

1DLC
2364


ATOM
2241
O
ASP
335
35.592
31.359
55.040
1.00
17.59

1DLC
2365


ATOM
2242
CB
ASP
335
33.941
30.783
58.058
1.00
15.88

1DLC
2366


ATOM
2243
CG
ASP
335
32.678
30.752
57.198
1.00
17.94

1DLC
2367


ATOM
2244
OD1
ASP
335
32.750
30.903
55.958
1.00
17.49

1DLC
2368


ATOM
2245
OD2
ASP
335
31.595
30.553
57.780
1.00
20.32

1DLC
2369


ATOM
2246
N
TYR
336
35.922
29.498
56.248
1.00
15.68

1DLC
2370


ATOM
2247
CA
TYR
336
36.415
28.728
55.109
1.00
17.74

1DLC
2371


ATOM
2248
C
TYR
336
35.711
27.387
54.888
1.00
17.85

1DLC
2372


ATOM
2249
O
TYR
336
35.266
26.734
55.836
1.00
17.36

1DLC
2373


ATOM
2250
CB
TYR
336
37.918
28.494
55.284
1.00
18.22

1DLC
2374


ATOM
2251
CO
TYR
336
38.700
29.753
55.593
1.00
21.42

1DLC
2375


ATOM
2252
CD1
TYR
336
38.688
30.310
56.874
1.00
20.91

1DLC
2376


ATOM
2253
CD2
TYR
336
39.437
30.398
54.597
1.00
23.29

1DLC
2377


ATOM
2254
CE1
TYR
336
39.389
31.481
57.153
1.00
25.49

1DLC
2378


ATOM
2255
CE2
TYR
336
40.147
31.567
54.865
1.00
24.79

1DLC
2379


ATOM
2256
CZ
TYR
336
40.119
32.105
56.142
1.00
25.10

1DLC
2380


ATOM
2257
OH 
TYR
336
40.820
33.262
56.402
1.00
25.35

1DLC
2381


ATOM
2258
N
LEU
337
35.634
26.968
53.631
1.00
17.01

1DLC
2382


ATOM
2259
CA
LEU
337
34.999
25.701
53.284
1.00
22.05

1DLC
2383


ATOM
2260
C
LEU
337
35.753
24.564
53.983
1.00
25.09

1DLC
2384


ATOM
2261
O
LEU
337
36.971
24.429
53.851
1.00
27.06

1DLC
2385


ATOM
2262
CB
LEU
337
35.041
25.493
51.765
1.00
19.73

1DLC
2386


ATOM
2263
CG
LEU
337
34.001
24.618
51.045
1.00
20.25

1DLC
2387


ATOM
2264
CD1
LEU
337
34.715
23.668
50.117
1.00
16.93

1DLC
2388


ATOM
2265
CD2
LEU
337
33.109
23.867
52.007
1.00
15.63

1DLC
2389


ATOM
2266
N
HIS
338
35.038
23.753
54.746
1.00
27.56

1DLC
2390


ATOM
2267
CA
HIS
338
35.886
22.654
55.447
1.00
32.45

1DLC
2391


ATOM
2268
C
HIS
338
35.223
21.263
55.002
1.00
35.61

1DLC
2392


ATOM
2269
O
HIS
338
36.040
20.350
54.825
1.00
37.52

1DLC
2393


ATOM
2270
CB
HIS
338
35.485
22.810
56.952
1.00
31.95

1DLC
2394


ATOM
2271
CG
HIS
338
36.423
21.983
57.771
1.00
35.39

1DLC
2395


ATOM
2272
ND1
HIS
338
36.028
20.835
58.424
1.00
39.61

1DLC
2396


ATOM
2273
CD2
HIS
338
37.740
22.140
58.047
1.00
35.97

1DLC
2397


ATOM
2274
CE1
HIS
338
37.060
20.320
59.070
1.00
39.82

1DLC
2398


ATOM
2275
NE2
HIS
338
38.110
21.093
58.856
1.00
39.08

1DLC
2399


ATOM
2276
N
ARG
339
33.918
21.111
54.801
1.00
36.63

1DLC
2400


ATOM
2277
CA
ARG
339
33.361
19.824
54.417
1.00
37.71

1DLC
2401


ATOM
2278
C
ARG
339
32.016
19.949
53.704
1.00
35.21

1DLC
2402


ATOM
2279
O
ARG
339
31.294
20.926
53.689
1.00
34.83

1DLC
2403


ATOM
2260
CB
ARG
339
33.231
18.972
55.684
1.00
41.00

1DLC
2404


ATOM
2701
CC 
ARG
339
32.608
17.602
55.526
1.00
48.56

1DLC
2405


ATOM
2282
CD
ARG
339
33.140
16.657
56.611
1.00
57.10

1DLC
2406


ATOM
2283
NE
ARG
339
33.391
17.338
57.888
1.00
62.49

1DLC
2407


ATOM
2284
CZ
ARG
339
34.520
17.235
58.597
1.00
63.78

1DLC
2408


ATOM
2285
NH1
ARG
339
35.521
16.474
58.171
1.00
61.26

1DLC
2409


ATOM
2286
NH2
AEG
339
34.651
17.905
59.739
1.00
63.23

1DLC
2410


ATOM
2287
N
ILE
340
31.717
18.981
52.642
1.00
33.04

1DLC
2411


ATOM
2288
CA
ILE
340
30.449
18.957
52.113
1.00
31.15

1DLC
2412


ATOM
2289
C
ILE
340
29.828
17.554
52.094
1.00
31.37

1DLC
2413


ATOM
2290
O
ILE
340
30.512
16.560
51.809
1.00
32.64

1DLC
2414


ATOM
2291
CB
ILE
340
30.594
19.440
50.642
1.00
28.39

1DLC
2415


ATOM
2292
CG1
ILE
340
31.263
20.812
50.588
1.00
26.45

1DLC
2416


ATOM
2293
CG2
ILE
340
29.204
19.547
49.988
1.00
23.66

1DLC
2417


ATOM
2294
CD1
ILE
340
31.491
21.316
49.181
1.00
23.48

1DLC
2418


ATOM
2295
N
GLN
341
28.542
17.475
52.430
1.00
29.86

1DLC
2419


ATOM
2296
CA
GLN
341
27.831
16.202
52.415
1.00
28.77

1DLC
2420


ATOM
2297
C
GLN
341
26.799
16.150
51.292
1.00
27.86

1DLC
2421


ATOM
2298
O
GLN
341
25.717
16.733
51.391
1.00
29.80

1DLC
2422


ATOM
2299
CB
GLN
341
27.153
15.903
53.752
1.00
27.96

1DLC
2423


ATOM
2300
CG
GLN
341
26.387
14.584
53.704
1.00
34.48

1DLC
2424


ATOM
2301
CD
GLN
341
25.905
14.100
55.057
1.00
37.10

1DLC
2425


ATOM
2302
NE1
GLN
341
24.703
13.989
55.297
1.00
39.41

1DLC
2428


ATOM
2303
NE2
GLN
341
26.834
13.776
55.932
1.00
37.66

1DLC
2427


ATOM
2304
N
PHE
342
27.143
15.439
50.228
1.00
27.45

1DLC
2428


ATOM
2305
CA
PHE
342
26.264
15.287
49.076
1.00
28.97

1DLC
2429


ATOM
2306
C
PHE
342
25.153
14.251
49.253
1.00
29.10

1DLC
2430


ATOM
2307
O
PHE
342
25.377
13.152
49.760
1.00
30.40

1DLC
2431


ATOM
2308
CB
PHE
342
27.081
14.942
47.831
1.00
27.31

1DLC
2432


ATOM
2309
CG
PHE
342
27.994
16.038
47.389
1.00
26.99

1DLC
2433


ATOM
2310
CD1
PHE
342
29.200
16.257
48.036
1.00
28.62

1DLC
2434


ATOM
2311
CD2
PHE
342
27.646
16.860
46.327
1.00
27.99

1DLC
2435


ATOM
2312
CE1
PHE
342
30.045
17.281
47.631
1.00
29.72

1DLC
2436


ATOM
2313
CE2
PHE
342
28.484
17.886
45.915
1.00
28.28

1DLC
2437


ATOM
2314
CZ 
PHE
342
29.684
18.096
46.568
1.00
29.89

1DLC
2438


ATOM
2315
N
HIS
343
23.936
14.647
48.898
1.00
31.24

1DLC
2439


ATOM
2316
CA
HIS
343
22.780
13.760
48.966
1.00
30.73

1DLC
2440


ATOM
2317
C
HIS
343
22.330
13.517
47.544
1.00
30.25

1DLC
2441


ATOM
2319
O
HIS
343
22.214
14.456
46.760
1.00
30.83

1DLC
2442


ATOM
2319
CH
HIS
343
21.644
14.367
49.786
1.00
27.80

1DLC
2443


ATOM
2320
CG
HIS
343
21.840
14.231
51.263
1.00
28.77

1DLC
2444


ATOM
2321
ND1
HIS
343
22.925
14.766
51.922
1.00
32.44

1DLC
2445


ATOM
2322
CD2
HIS
343
21.101
13.601
52.207
1.00
27.79

1DLC
2446


ATOM
2323
CE1
HIS
343
22.849
14.472
53.205
1.00
30.66

1DLC
2447


ATOM
2324
NE2
HIS
343
21.751
13.766
53.404
1.00
30.61

1DLC
2448


ATOM
2325
N
THR
344
22.118
12.248
47.214
1.00
30.51

1DLC
2449


ATOM
2326
CA
THR
344
21.707
11.853
45.873
1.00
30.88

1DLC
2450


ATOM
2327
C
THR
344
20.344
11.154
45.812
1.00
33.44

1DLC
2451


ATOM
2328
O
TER
344
19.928
10.442
46.744
1.00
32.56

1DLC
2452


ATOM
2329
CB
THR
344
22.775
10.938
45.225
1.00
26.81

1DLC
2453


ATOM
2330
OG1
THR
344
24.046
11.597
45.262
1.00
29.11

1DLC
2454


ATOM
2331
CG2
THR
344
22.430
10.614
43.785
1.00
24.42

1DLC
2455


ATOM
2332
N
ARG
345
19.655
11.385
44.698
1.00
32.36

1DLC
2456


ATOM
2333
CA
ARG
345
18.352
10.796
44.433
1.00
29.58

1DLC
2457


ATOM
2334
C
ARG
345
18.289
10.272
43.010
1.00
29.62

1DLC
2458


ATOM
2335
O
ARG
345
19.079
10.681
42.145
1.00
27.21

1DLC
2459


ATOM
2336
CB
ARG
345
17.233
11.812
44.659
1.00
26.82

1DLC
2460


ATOM
2337
CG
ARG
345
16.905
12.019
46.118
1.00
25.81

1DLC
2461


ATOM
2338
CD
ARG
345
15.509
12.552
46.288
1.00
25.24

1DLC
2462


ATOM
2339
NE
ARG
345
15.127
12.531
47.692
1.00
30.00

1DLC
2463


ATOM
2340
CZ 
ARG
345
13.978
12.998
48.167
1.00
32.09

1DLC
2464


ATOM
2341
NH1
ARG
345
13.076
13.525
47.348
1.00
32.16

1DLC
2465


ATOM
2342
NH2
ARG 
345
13.749
12.978
49.473
1.00
33.30

1DLC
2466


ATOM
2343
N
PHE
345
17.391
9.316
42.796
1.00
27.16

1DLC
2467


ATOM
2344
CA
PHE
346
17.193
8.715
41.497
1.00
26.42

1DLC
2468


ATOM
2345
C
PHE
346
16.082
9.404
40.701
1.00
26.65

1DLC
2469


ATOM
2346
O
PHE
346
15.003
9.651
41.224
1.00
27.28

1DLC
2470


ATOM
2347
CB
PHE
346
16.875
7.222
41.633
1.00
25.70

1DLC
2471


ATOM
2348
CG
PHE
346
16.431
6.565
40.349
1.00
24.42

1DLC
2472


ATOM
2349
CD1
PHE
346
17.296
6.461
39.267
1.00
25.47

1DLC
2473


ATOM
2350
CD2
PHE
346
15.145
6.057
40.222
1.00
24.17

1DLC
2474


ATOM
2351
CE1
PHE
346
16.884
5.863
38.079
1.00
26.24

1DLC
2475


ATOM
2352
CE2
PHE
346
14.726
5.457
39.037
1.00
22.53

1DLC
2475


ATOM
2353
CZ 
PHE
346
15.594
5.359
37.966
1.00
22.75

1DLC
2477


ATOM
2354
N
GLN
347
16.365
9.747
39.452
1.00
26.19

1DLC
2478


ATOM
2355
CA
GLN
347
15.361
10.368
38.602
1.00
28.50

1DLC
2479


ATOM
2356
C
GLN
347
15.031
9.390
37.497
1.00
29.83

1DLC
2480


ATOM
2357
O
GLN
347
15.876
9.075
36.643
1.00
29.71

1DLC
2481


ATOM
2358
CB
GLN
347
15.840
11.692
38.001
1.00
30.26

1DLC
2482


ATOM
2359
CU
GLN
347
14.880
12.280
36.951
1.00
29.03

1DLC
2483


ATOM
2360
CD
GLN
347
13.454
12.473
37.471
1.00
31.21

1DLC
2484


ATOM
2361
OE1
GLN
347
13.234
13.083
38.515
1.00
31.71

1DLC
2485


ATOM
2362
NE2
GLN
347
12.482
11.949
36.739
1.00
34.89

1DLC
2486


ATOM
2363
N
PRO
348
13.816
8.831
37.537
1.00
29.99

1DLC
2487


ATOM
2364
CA
PRO
348
13.392
7.873
36.521
1.00
30.56

1DLC
2488


ATOM
2365
C
PRO
348
13.079
8.512
35.180
1.00
31.08

1DLC
2489


ATOM
2366
O
PRO
348
12.571
9.630
35.109
1.00
29.47

1DLC
2490


ATOM
2367
CB
PRO
348
12.148
7.249
37.146
1.00
30.82

1DLC
2491


ATOM
2368
CG
PRO
348
11.586
8.367
37.960
1.00
28.95

1DLC
2492


ATOM
2369
CD
PRO
348
12.814
8.934
38.613
1.00
28.01

1DLC
2493


ATOM
2370
N
GLY
349
13.494
7.835
34.122
1.00
32.08

1DLC
2494


ATOM
2371
CA
GLY
349
13.203
8.310
32.788
1.00
36.84

1DLC
2495


ATOM
2372
C
GLY
349
11.906
7.627
32.382
1.00
40.08

1DLC
2496


ATOM
2373
O
GLY
349
11.629
6.511
32.825
1.00
39.90

1DLC
2497


ATOM
2374
N
TYR
350
11.103
8.277
31.550
1.00
42.86

1DLC
2498


ATOM
2375
CA
TYR
350
9.836
7.697
31.119
1.00
42.49

1DLC
2499


ATOM
2376
C
TYR
350
9.976
6.282
30.548
1.00
42.42

1DLC
2500


ATOM
2377
O
TYR
350
9.096
5.447
30.742
1.00
38.59

1DLC
2501


ATOM
2378
CB
TYR
350
9.157
8.611
30.107
1.00
41.54

1DLC
2502


ATOM
2379
CG
TYR
350
7.723
8.243
29.846
1.00
42.11

1DLC
2503


ATOM
2380
CD
TYR
350
6.758
8.372
30.846
1.00
42.70

1DLC
2504


ATOM
2381
CD2
TYR
350
7.323
7.778
29.597
1.00
41.41

1DLC
2505


ATOM
2382
CE1
TYR
350
5.428
8.051
30.604
1.00
43.17

1DLC
2506


ATOM
2383
CE2
TYR
350
6.002
7.453
28.345
1.00
44.30

1DLC
2507


ATOM
2384
CZ 
TYR
350
5.060
7.594
29.350
1.00
44.01

1DLC
2508


ATOM
2385
OH 
TYR
350
3.751
7.285
29.084
1.00
51.17

1DLC
2509


ATOM
2386
N
TYR
351
11.091
6.013
29.870
1.00
46.30

1DLC
2510


ATOM
2387
CA
TYR
351
11.342
4.689
29.293
1.00
49.39

1DLC
2511


ATOM
2388
C
TYR
351
12.413
3.853
30.005
1.00
50.19

1DLC
2512


ATOM
2389
O
TYR
351
12.900
2.862
29.459
1.00
49.12

1DLC
2513


ATOM
2390
CB
TYR
351
11.660
4.807
27.805
1.00
52.75

1DLC
2514


ATOM
2391
CG
TYR
351
10.484
5.296
27.001
1.00
59.62

1DLC
2515


ATOM
2392
CD1
TYR
351
9.431
4.437
26.674
1.00
60.34

1DLC
2516


ATOM
2393
CD2
TYR
351
10.401
6.629
26.596
1.00
62.29

1DLC
2517


ATOM
2394
CE1
TYR
351
8.324
4.896
25.964
1.00
62.98

1DLC
2518


ATOM
2395
CE2
TYR
351
9.299
7.101
25.888
1.00
64.82

1DLC
2519


ATOM
2396
CZ 
TYR
351
8.263
6.231
25.577
1.00
66.21

1DLC
2520


ATOM
2397
OH 
TYR
351
7.167
6.710
24.891
1.00
71.16

1DLC
2521


ATOM
2398
N
GLY
352
12.764
4.247
31.229
1.00
51.80

1DLC
2522


ATOM
2399
CA
GLY
352
13.756
3.519
32.013
1.00
54.02

1DLC
2523


ATOM
2400
C
GLY
352
15.203
3.694
31.585
1.00
54.76

1DLC
2524


ATOM
2401
O
GLY
352
16.086
3.933
32.407
1.00
56.76

1DLC
2525


ATOM
2402
N
ASN
353
15.439
3.562
30.289
1.00
54.09

1DLC
2526


ATOM
2403
CA
ASN
353
16.768
3.700
29.702
1.00
54.37

1DLC
2527


ATOM
2404
C
ASN
353
17.383
5.096
29.857
1.00
52.91

1DLC
2528


ATOM
2405
O
ASN
353
18.599
5.253
29.836
1.00
53.09

1DLC
2529


ATOM
2406
CB
ASN
353
16.685
3.347
28.216
1.00
58.15

1DLC
2530


ATOM
2407
CG
ASN
353
15.459
3.949
27.538
1.00
61.25

1DLC
2531


ATOM
2408
OD1
ASN
353
15.047
5.069
27.845
1.00
63.28

1DLC
2512


ATOM
2409
ND2
ASN
353
14.855
3.194
26.635
1.00
64.45

1DLC
2533


ATOM
2410
N
ASP
354
16.528
6.097
30.021
1.00
50.29

1DLC
2534


ATOM
2411
CA
ASP
354
16.961
7.488
30.140
1.00
46.56

1DLC
2535


ATOM
2412
C
ASP
354
17.013
8.056
31.560
1.00
45.20

1DLC
2536


ATOM
2413
O
ASP
354
16.987
9.277
31.759
1.00
41.77

1DLC
2537


ATOM
2414
CB
ASP
354
16.062
8.362
29.269
1.00
47.89

1DLC
2538


ATOM
2415
CG
ASP
354
14.594
8.263
29.652
1.00
49.69

1DLC
2539


ATOM
2416
OD1
ASP
354
14.110
7.156
29.988
1.00
49.83

1DLC
2540


ATOM
2417
OD2
ASP
354
13.921
9.309
29.616
1.00
53.54

1DLC
2541


ATOM
2418
N
SER
355
17.088
7.170
32.545
1.00
42.98

1DLC
2542


ATOM
2419
CA
SER
355
17.141
7.582
33.946
1.00
42.29

1DLC
2543


ATOM
2420
C
SER
355
18.522
8.087
34.354
1.00
39.61

1DLC
2544


ATOM
2421
O
SER
355
19.501
7.891
33.636
1.00
40.89

1DLC
2545


ATOM
2422
CB
SER
355
16.752
6.407
34.837
1.00
45.53

1DLC
2546


ATOM
2423
OG
SER
355
15.491
5.879
34.453
1.00
49.12

1DLC
2547


ATOM
2424
N
PHE
356
18.595
8.753
35.500
1.00
35.84

1DLC
2548


ATOM
2425
CA
PHE
356
19.863
9.268
36.013
1.00
33.36

1DLC
2549


ATOM
2426
C
PHE
356
19.735
9.633
37.486
1.00
33.41

1DLC
2550


ATOM
2427
O
PHE
356
18.626
9.773
38.006
1.00
33.51

1DLC
2551


ATOM
2428
CB
PHE
356
20.358
10.484
35.200
1.00
30.78

1DLC
2552


ATOM
2429
CG
PHE
356
19.510
11.727
35.353
1.00
30.29

1DLC
2553


ATOM
2430
CD1
PHE
356
18.374
11.921
34.568
1.00
30.93

1DLC
2554


ATOM
2431
CD2
PHE
356
19.849
12.709
36.278
1.00
29.49

1DLC
2555


ATOM
2432
CE1
PHE
356
17.592
13.073
34.708
1.00
27.44

1DLC
2556


ATOM
2433
CE2
PHE
356
19.071
13.864
36.424
1.00
26.60

1DLC
2557


ATOM
2434
CZ
PHE
356
17.946
4.044
35.640
1.00
27.20

1DLC
2558


ATOM
2435
N
ASN
357
20.864
9.665
38.183
1.00
34.56

1DLC
2559


ATOM
2436
CA
ASN
357
20.883
10.051
39.594
1.00
34.66

1DLC
2560


ATOM
2437
C
ASN
357
21.299
11.510
39.637
1.00
31.40

1DLC
2561


ATOM
2438
O
ASN
357
21.977
11.990
38.726
1.00
30.66

1DLC
2562


ATOM
2439
CB
ASN
357
21.892
9.221
40.385
1.00
38.51

1DLC
2563


ATOM
2440
CG
ASN
357
21.411
7.816
40.656
1.00
40.71

1DLC
2564


ATOM
2441
OD1
ASN
357
22.211
6.921
40.897
1.00
45.00

1DLC
2565


ATOM
2442
ND2
ASN
357
20.103
7.611
40.629
1.00
42.48

1DLC
2566


ATOM
2443
N
TYR
358
20.923
12.219
40.688
1.00
27.67

1DLC
2567


ATOM
2444
CA
TYR
358
21.294
13.620
40.758
1.00
26.55

1DLC
2568


ATOM
2445
C
TYR
358
21.457
14.115
42.186
1.00
26.59

1DLC
2569


ATOM
2446
O
TYR
358
20.937
13.521
43.132
1.00
24.94

1DLC
2570


ATOM
2447
CB
TYR
358
20.272
14.483
39.999
1.00
25.94

1DLC
2571


ATOM
2448
CG
TYR
358
18.936
14.566
40.683
1.00
27.85

1DLC
2572


ATOM
2449
CD1
TYR
358
17.962
13.584
40.461
1.00
31.47

1DLC
2573


ATOM
2450
CD2
TYR
358
18.679
15.546
41.630
1.00
32.37

1DLC
2574


ATOM
2451
CE1
TYR
358
16.765
13.587
41.180
1.00
34.73

1DLC
2575


ATOM
2452
CE2
TYR
358
17.494
15.562
42.354
1.00
36.61

1DLC
2576


ATOM
2453
CZ 
TYR
358
16.541
14.581
42.131
1.00
38.10

1DLC
2577


ATOM
2454
OH
TYR
358
15.384
14.586
42.886
1.00
45.04

1DLC
2578


ATOM
2455
N
TRP
359
22.212
15.200
42.318
1.00
27.94

1DLC
2579


ATOM
2456
CA
TRP
359
22.487
15.852
43.596
1.00
26.27

1DLC
2580


ATOM
2457
C
TRP
359
21.183
16.510
44.063
1.00
24.40

1DLC
2581


ATOM
2458
O
TRP
399
20.694
17.462
43.449
1.00
25.89

1DLC
2582


ATOM
2459
CR 
TRP
359
23.596
16.890
43.382
1.00
23.83

1DLC
2583


ATOM
2460
CG
TRP
359
24.070
17.584
44.604
1.00
23.65

1DLC
2584


ATOM
2461
CD1
TRP
359
23.782
17.267
45.901
1.00
25.90

1DLC
2585


ATOM
2462
CD2
TRP
359
24.919
18.733
44.649
1.00
25.70

1DLC
2586


ATOM
2463
NE1
TRP
359
24.396
18.152
46.752
1.00
25.43

1DLC
2587


ATOM
2464
CE2
TRP
359
25.103
19.062
46.011
1.00
27.53

1DLC
2588


ATOM
2465
CE3
TRP
359
25.547
19.518
43.669
1.00
26.62

1DLC
2589


ATOM
2466
CZ2
TRP
359
25.894
20.147
46.419
1.00
27.25

1DLC
2590


ATOM
2467
CZ3
TRP
359
26.333
20.596
44.075
1.00
25.15

1DLC
2591


ATOM
2468
CH2
TRP
359
26.498
20.897
45.437
1.00
26.00

1DLC
2592


ATOM
2469
N
SER
360
20.610
15.977
45.132
1.00
22.69

1DLC
2593


ATOM
2470
CA
SER
360
19.339
16.473
45.654
1.00
23.95

1DLC
2594


ATOM
2471
C
SER
360
19.405
17.470
46.812
1.00
25.02

1DLC
2595


ATOM
2472
O
SER
360
18.520
18.317
46.966
1.00
26.55

1DLC
2596


ATOM
2473
CB
SER
360
18.460
15.289
46.060
1.00
22.05

1DLC
2597


ATOM
2474
OG 
SER
360
19.050
14.555
47.123
1.00
20.36

1DLC
2598


ATOM
2475
N
GLY
361
20.422
17.345
47.653
1.00
23.75

1DLC
2599


ATOM
2476
CA
GLY
361
20.542
18.246
48.782
1.00
21.17

1DLC
2600


ATOM
2477
C
GLY
361
21.935
18.193
49.361
1.00
24.69

1DLC
2601


ATOM
2478
O
GLY
361
22.789
17.443
48.871
1.00
26.41

1DLC
2602


ATOM
2479
N
ASN
362
22.181
18.955
50.419
1.00
22.30

1DLC
2603


ATOM
2480
CA
ASN
362
23.510
18.954
51.003
1.00
22.20

1DLC
2604


ATOM
2481
C
ASN
362
23.590
19.569
52.381
1.00
21.51

1DLC
2605


ATOM
2482
O
ASN
362
22.543
20.179
52.871
1.00
20.57

1DLC
2606


ATOM
2483
CB
ASN
362
24.485
19.713
50.089
1.00
24.04

1DLC
2607


ATOM
2484
CO 
ASN
362
24.420
21.228
50.291
1.00
28.34

1DLC
2608


ATOM
2485
OD1
ASN
362
25.165
21.789
51.088
1.00
28.65

1DLC
2609


ATOM
2486
ND2
ASN
362
23.516
21.885
49.593
1.00
26.03

1DLC
2610


ATOM
2487
N
TYR
363
24.743
19.346
52.993
1.00
24.00

1DLC
2611


ATOM
2488
CA
TYR
363
25.110
19.902
54.286
1.00
26.62

1DLC
2612


ATOM
2489
C
TYR
363
26.466
20.551
53.960
1.00
28.28

1DL
2613


ATOM
2490
O
TYR
363
27.191
20.085
53.067
1.00
27.60

1DLC
2614


ATOM
2491
CB
TYR
363
25.381
18.810
55.329
1.00
27.58

1DLC
2615


ATOM
2492
CG
TYR
363
24.178
18.317
56.087
1.00
28.34

1DLC
2616


ATOM
2493
CD1
TYR
363
23.515
19.138
56.997
1.00
29.04

1DLC
2617


ATOM
2494
CD2
TYR
363
23.719
17.016
55.915
1.00
30.38

1DLC
2618


ATOM
2495
CE1
TYR
363
22.425
18.672
57.718
1.00
32.23

1DLC
2619


ATOM
2496
CE2
TYR
363
22.630
16.537
56.620
1.00
33.13

1DLC
2620


ATOM
2497
CZ 
TYR
363
21.985
17.366
57.529
1.00
34.94

1DLC
2621


ATOM
2498
OH
TYR
363
20.902
16.876
58.232
1.00
36.70

1DLC
2622


ATOM
2499
N
VAL
364
26.791
21.640
54.641
1.00
28.34

1DLC
2623


ATOM
2500
CA
VAL
364
28.075
22.294
54.431
1.00
26.27

1DLC
2624


ATOM
2501
C
VAL
364
28.651
22.630
55.790
1.00
24.54

1DLC
2625


ATOM
2502
O
VAL
364
27.923
22.972
56.722
1.00
27.34

1DLC
2626


ATOM
2503
CB
VAL
364
27.957
23.592
53.612
1.00
28.72

1DLC
2627


ATOM
2504
CG1
VAL
364
29.333
24.079
53.197
1.00
30.77

1DLC
2628


ATOM
2505
CG2
VAL
364
27.135
23.356
52.393
1.00
16.32

1DLC
2629


ATOM
2506
N
SER
365
29.953
22.456
55.920
1.00
24.40

1DLC
2630


ATOM
2507
CA
SER
365
30.639
22.766
57.166
1.00
24.54

1DLC
2631


ATOM
2508
C
SER
365
31.804
23.688
56.850
1.00
23.42

1DLC
2632


ATOM
2509
O
SER
365
32.538
23.477
55.883
1.00
21.82

1DLC
2633


ATOM
2510
CS 
SER
365
31.166
21.496
57.845
1.00
27.44

1DLC
2634


ATOM
2511
OG
SER
365
30.117
20.716
58.400
1.00
34.19

1DLC
2635


ATOM
2512
N
THR
366
31.938
24.737
57.645
1.00
21.84

1DLC
2636


ATOM
2513
CA
THR
366
33.018
25.690
57.469
1.00
23.59

1DLC
2637


ATOM
2514
C
THR
366
33.789
25.846
58.767
1.00
24.57

1DLC
2638


ATOM
2515
O
THR
366
33.265
25.580
59.851
1.00
21.97

1DLC
2639


ATOM
2516
CB
THR
366
32.502
27.105
57.062
1.00
22.30

1DLC
2640


ATOM
2517
OG1
THR
366
31.532
27.558
58.015
1.00
21.18

1DLC
2641


ATOM
2518
CG2
THR
366
31.913
27.107
55.641
1.00
16.40

1DLC
2642


ATOM
2519
N
ARG
367
35.060
26.198
58.654
1.00
23.66

1DLC
2643


ATOM
2520
CA
ARG
367
35.843
26.439
59.849
1.00
25.59

1DLC
2644


ATOM
2521
C
ARG
367
35.989
27.960
59.945
1.00
25.50

1DLC
2645


ATOM
2522
O
ARG
367
36.029
28.663
58.923
1.00
23.62

1DLC
2646


ATOM
2523
CB
ARG
367
37.201
25.721
59.819
1.00
28.50

1DLC
2647


ATOM
2524
CG
ARG
367
38.231
26.244
58.838
1.00
33.38

1DLC
2648


ATOM
2525
CD
ARG
367
39.617
26.227
59.483
1.00
39.84

1DLC
2649


ATOM
2526
NE 
ARG
367
39.715
27.236
60.538
1.00
46.62

1DLC
2650


ATOM
2527
CZ 
ARG
367
40.452
27.122
61.642
1.00
47.81

1DLC
2651


ATOM
2528
NH1
ARG
367
41.174
26.027
61.857
1.00
49.54

1DLC
2652


ATOM
2529
NH2
ARG
367
40.473
26.114
62.528
1.00
42.81

1DLC
2653


ATOM
2530
N
PRO
368
35.927
28.497
61.167
1.00
25.39

1DLC
2654


ATOM
2531
CA
PRO
368
36.055
29.944
61.357
1.00
24.95

1DLC
2655


ATOM
2532
C
PRO
368
37.430
30.514
61.038
1.00
25.37

1DLC
2656


ATOM
2533
O
PRO
368
38.312
29.832
60.517
1.00
25.73

1DLC
2657


ATOM
2534
CB
PRO
368
35.695
30.131
62.833
1.00
23.10

1DLC
2658


ATOM
2535
CG
PRO
368
36.052
28.813
63.453
1.00
27.44

1DLC
2659


ATOM
2536
CD
PRO
368
35.568
27.826
62.427
1.00
25.33

1DLC
2660


ATOM
2537
N
SER
369
37.582
31.800
61.301
1.00
25.94

1DLC
2661


ATOM
2538
CA
SER
369
38.849
32.470
61.075
1.00
28.16

1DLC
2662


ATOM
2539
C
SER
369
39.857
31.953
62.126
1.00
30.36

1DLC
2663


ATOM
2540
O
SER
369
39.459
31.446
63.195
1.00
27.15

1DLC
2664


ATOM
2541
CB
SER
369
38.647
33.983
61.205
1.00
28.25

1DLC
2665


ATOM
2542
OG
SER
369
39.797
34.702
60.811
1.00
31.44

1DLC
2666


ATOM
2543
N
ILE
370
41.151
32.051
61.813
1.00
27.89

1DLC
2667


ATOM
2544
CA
ILE
370
42.198
31.602
62.731
1.00
26.08

1DLC
2668


ATOM
2545
C
ILE
370
41.936
32.085
64.169
1.00
25.65

1DLC
2669


ATOM
2546
O
ILE
370
41.477
33.208
64.388
1.00
24.58

1DLC
2670


ATOM
2547
CB
ILE
370
43.612
32.047
62.241
1.00
28.63

1DLC
2671


ATOM
2548
CG1
ILE
370
44.695
31.410
63.116
1.00
28.81

1DLC
2672


ATOM
2549
CG2
ILE
370
43.749
33.576
62.236
1.00
24.11

1DLC
2673


ATOM
2550
CD1
ILE
370
46.064
31.482
62.521
1.00
22.91

1DLC
2674


ATOM
2551
N
GLY
371
42.179
31.218
65.143
1.00
26.12

1DLC
2675


ATOM
2552
CA
GLY
371
41.934
31.588
66.526
1.00
27.59

1DLC
2676


ATOM
2553
C
GLY
371
40.831
30.742
67.132
1.00
31.60

1DLC
2677


ATOM
2554
O
GLY
371
40.728
30.608
68.347
1.00
32.87

1DLC
2678


ATOM
2555
N
SER
372
39.973
30.198
66.279
1.00
34.07

1DLC
2679


ATOM
2556
CA
SER
372
36.806
29.334
66.733
1.00
38.39

1DLC
2680


ATOM
2557
C
SER
372
38.918
28.050
65.926
1.00
42.67

1DLC
2681


ATOM
2558
O
SER
372
39.225
28.058
64.731
1.00
45.63

1DLC
2682


ATOM
2559
CB
SER
372
37.522
30.000
66.553
1.00
37.68

1DLC
2683


ATOM
2560
OG
SER
372
36.484
29.117
66.945
1.00
35.42

1DLC
2684


ATOM
2561
N
ASN
373
38.605
26.940
66.571
1.00
45.05

1DLC
2685


ATOM
2562
CA
ASN
373
38.624
25.669
65.869
1.00
49.01

1DLC
2686


ATOM
2563
C
ASN
373
37.271
24.961
65.761
1.00
49.16

1DLC
2687


ATOM
2564
O
ASN
373
37.158
23.940
65.078
1.00
50.24

1DLC
2688


ATOM
2565
CB
ASN
373
39.670
24.745
66.501
1.00
53.82

1DLC
2689


ATOM
2566
CG
ASN
373
41.091
25.214
66.246
1.00
58.42

1DLC
2690


ATOM
2567
OD1
ASN
373
41.791
25.640
67.163
1.00
62.66

1DLC
2691


ATOM
2558
ND2
ASN
373
41.523
25.148
64.992
1.00
60.46

1DLC
2692


ATOM
2569
N
ASP
374
36.239
25.502
66.403
1.00
47.14

1DLC
2693


ATOM
2570
CA
ASP
374
34.941
24.849
68.331
1.00
48.54

1DLC
2694


ATOM
2571
C
ASP
374
34.255
25.010
64.975
1.00
45.07

1DLC
2695


ATOM
2572
O
ASP
374
33.989
26.120
64.514
1.00
43.01

1DLC
2696


ATOM
2573
CB
ASP
374
34.028
25.232
67.506
1.00
55.25

1DLC
2697


ATOM
2574
CG
ASP
374
33.826
26.723
67.644
1.00
62.12

1DLC
2898


ATOM
2575
OD1
ASP
374
33.068
27.308
66.835
1.00
68.28

1DLC
2699


ATOM
2576
OD2
ASP
374
34.403
27.303
68.590
1.00
66.38

1DLC
2700


ATOM
2577
N
ILE
375
34.029
23.868
64.335
1.00
41.73

1DLC
2701


ATOM
2578
CA
ILE
375
33.408
23.776
63.020
1.00
37.95

1DLC
2702


ATOM
2579
C
ILE
375
31.921
24.131
63.008
1.00
36.63

1DLC
2703


ATOM
2580
O
ILE
375
31.143
23.638
63.816
1.00
38.76

1DLC
2704


ATOM
2581
CR
ILE
375
33.618
22.355
62.428
1.00
36.39

1DLC
2705


ATOM
2582
CG1
ILE
375
35.110
22.015
62.422
1.00
36.11

1DLC
2706


ATOM
2583
CG2
ILE
375
33.056
22.254
61.014
1.00
35.62

1DLC
2707


ATOM
2584
CD1
ILE
375
35.966
22.993
61.658
1.00
34.10

1DLC
2708


ATOM
2585
N
ILE
376
31.541
25.001
62.084
1.00
35.72

1DLC
2709


ATOM
2586
CA
ILE
376
30.156
25.428
61.942
1.00
31.79

1DLC
2710


ATOM
2587
C
ILE
376
29.478
24.575
60.863
1.00
31.77

1DLC
2711


ATOM
2588
O
ILE
376
29.948
24.483
59.751
1.00
32.62

1DLC
2712


ATOM
2589
CS
ILE
376
30.077
26.885
61.481
1.00
31.87

1DLC
2713


ATOM
2590
CG1
ILE
376
30.864
27.781
62.432
1.00
27.90

1DLC
2714


ATOM
2591
CG2
ILE
376
28.632
27.324
61.391
1.00
28.10

1DLC
2715


ATOM
2592
CD1
ILE
376
31.122
29.148
61.868
1.00
30.02

1DLC
2716


ATOM
2593
N
THR
377
28.390
23.921
61.250
1.00
31.76

1DLC
2717


ATOM
2594
CA
THR
377
27.696
23.104
60.275
1.00
31.91

1DLC
2718


ATOM
2595
C
TER
377
26.337
23.687
59.972
1.00
31.49

1DLC
2719


ATOM
2596
O
THR
377
25.590
24.070
60.872
1.00
32.65

1DLC
2720


ATOM
2597
CB
TER
377
27.577
21.653
60.711
1.00
32.50

1DLC
2721


ATOM
2598
OG1
THR
377
28.890
21.137
60.960
1.00
34.88

1DLC
2722


ATOM
2599
CG2
THR
377
26.937
20.833
59.601
1.00
36.51

1DLC
2723


ATOM
2600
N
SER
378
26.056
23.790
58.681
1.00
31.02

1DLC
2724


ATOM
2601
CA
SER
378
24.813
24.351
58.166
1.00
30.69

1DLC
2725


ATOM
2602
C
SER
378
23.570
23.484
58.326
1.00
30.61

1DLC
2726


ATOM
2503
O
SER
378
23.648
22.276
58.573
1.00
32.66

1DLC
2727


ATOM
2604
CR
SER
378
24.969
24.591
56.672
1.00
29.80

1DLC
2728


ATOM
2605
OG
SER
378
24.957
23.342
56.002
1.00
24.82

1DLC
2729


ATOM
2506
N
PRO
379
22.392
24.105
58.200
1.00
30.39

1DLC
2730


ATOM
2607
CA
PRO
379
21.155
23.332
58.313
1.00
29.82

1DLC
2731


ATOM
2608
C
PRO
379
21.130
22.476
57.042
1.00
29.81

1DLC
2732


ATOM
2609
O
PRO
379
21.967
22.660
56.154
1.00
31.85

1DLC
2733


ATOM
2610
CS
PRO
379
20.076
24.413
58.234
1.00
28.69

1DLC
2734


ATOM
2611
CO
PRO
379
20.761
25.632
58.763
1.00
29.56

1DLC
2735


ATOM
2612
CD
PRO
379
22.107
25.547
58.115
1.00
30.05

1DLC
2735


ATOM
2613
N
PHE
380
20.206
21.535
56.941
1.00
28.23

1DLC
2737


ATOM
2614
CA
PRE
360
20.154
20.740
55.727
1.00
27.04

1DLC
2738


ATOM
2615
C
PHE
380
19.513
21.568
54.606
1.00
26.98

1DLC
2739


ATOM
2616
O
PHE
380
18.578
22.335
54.850
1.00
29.48

1DLC
2740


ATOM
2617
CB
PHE
380
19.381
19.435
55.938
1.00
25.05

1DLC
2741


ATOM
2618
CO 
PHE
380
19.383
18.545
54.731
1.00
24.11

1DLC
2742


ATOM
2619
CD1
PRE
380
20.527
17.846
54.377
1.00
20.89

1DLC
2743


ATOM
2620
CD2
PHE
380
18.268
18.467
53.903
1.00
21.40

1DLC
2744


ATOM
2621
CE1
PRE
380
20.566
17.089
53.216
1.00
20.66

1DLC
2745


ATOM
2622
CE2
PHE
380
18.300
17.714
52.742
1.00
22.67

1DLC
2746


ATOM
2623
CZ
PHE
380
19.453
17.025
52.396
1.00
21.89

1DLC
2747


ATOM
2624
N
TYR
381
20.050
21.446
53.395
1.00
26.14

1DLC
2748


ATOM
2625
CA
TYR
381
19.525
22.167
52.241
1.00
25.56

1DLC
2749


ATOM
2626
C
TYR
381
19.056
21.183
51.182
1.00
28.82

1DLC
2750


ATOM
2627
O
TYR
381
19.812
20.291
50.797
1.00
31.78

1DLC
2751


ATOM
2628
CB
TYR
381
20.607
23.053
51.608
1.00
25.41

1DLC
2752


ATOM
2629
CG
TYR
381
21.187
24.117
52.512
1.00
25.18

1DLC
2753


ATOM
2630
CD1
TYR
381
20.375
25.090
53.087
1.00
23.16

1DLC
2754


ATOM
2631
CD2
TYR
381
22.558
24.162
52.779
1.00
21.71

1DLC
2755


ATOM
2632
CE1
TYR
381
20.914
26.080
53.905
1.00
24.57

1DLC
2756


ATOM
2633
CE2
TYR
381
23.101
25.148
53.592
1.00
20.00

1DLC
2757


ATOM
2634
CZ 
TYR
381
22.277
26.102
54.153
1.00
20.22

1DLC
2758


ATOM
2635
OH
TYR
381
22.797
27.071
54.980
1.00
21.73

1DLC
2759


ATOM
2636
N
GLY
382
17.828
21.358
50.696
1.00
30.75

1DLC
2760


ATOM
2637
CA
GLY
382
17.307
20.495
49.646
1.00
29.98

1DLC
2761


ATOM
2638
C
GLY
382
16.603
19.230
50.093
1.00
32.07

1DLC
2762


ATOM
2639
O
GLY
382
15.939
19.219
51.126
1.00
34.65

1DLC
2763


ATOM
2640
N
ASN
363
16.765
18.157
49.325
1.00
31.65

1DLC
2764


ATOM
2641
CA
ASN
383
16.123
16.877
49.632
1.00
31.34

1DLC
2765


ATOM
2642
C
ASN
383
17.023
15.758
50.136
1.00
29.92

1DLC
2766


ATOM
2643
O
ASN
383
18.083
15.493
49.567
1.00
28.55

1DLC
2767


ATOM
2644
CB
ASN
363
15.346
16.373
48.417
1.00
32.90

1DLC
2766


ATOM
2645
CO 
ASN
383
13.928
16.892
48.383
1.00
33.10

1DLC
2769


ATOM
2646
OD1
ASN
383
13.267
16.978
49.412
1.00
34.94

1DLC
2770


ATOM
2647
ND2
ASN
383
13.453
17.242
47.203
1.00
33.54

1DLC
2771


ATOM
2648
N
LYS
384
16.566
15.070
51.179
1.00
30.21

1DLC
2772


ATOM
2649
CA
LYS
384
17.318
13.959
51.755
1.00
30.31

1DLC
2773


ATOM
2650
C
LYS
384
17.691
12.931
50.696
1.00
29.47

1DLC
2774


ATOM
2651
O
LYS
384
17.039
12.806
49.666
1.00
30.67

1DLC
2775


ATOM
2652
CB
LYS
384
16.538
13.283
52.877
1.00
31.48

1DLC
2776


ATOM
2653
CG
LYS
384
16.309
14.156
54.090
1.00
37.12

1DLC
2777


ATOM
2654
CD
LYS
384
17.594
14.459
54.835
1.00
38.68

1DLC
2778


ATOM
2655
CE
LYS
384
17.275
15.123
56.166
1.00
43.15

1DLC
2779


ATOM
2656
NZ
LYS
384
18.485
15.319
57.010
1.00
50.78

1DLC
2780


ATOM
2657
N
SER
385
18.736
12.174
50.977
1.00
31.31

1DLC
2781


ATOM
2658
CA
SER
385
19.230
11.191
50.033
1.00
33.17

1DLC
2782


ATOM
2659
C
SER
385
18.391
9.923
49.935
1.00
34.75

1DLC
2783


ATOM
2660
O
SER
385
17.817
9.464
50.921
1.00
35.39

1DLC
2784


ATOM
2661
CB
SER
385
20.572
10.821
50.401
1.00
31.08

1DLC
2785


ATOM
2662
OG 
SER
385
21.444
10.511
49.254
1.00
29.79

1DLC
2786


ATOM
2663
N
SER
386
18.249
9.425
48.714
1.00
36.92

1DLC
2787


ATOM
2664
CA
SER
386
17.559
8.158
48.476
1.00
39.69

1DLC
2788


ATOM
2665
C
SER
386
18.713
7.175
48.234
1.00
41.41

1DLC
2789


ATOM
2666
O
SER
386
18.573
5.965
48.395
1.00
45.84

1DLC
2790


ATOM
2667
CB
SER
386
16.666
8.215
47.233
1.00
38.56

1DLC
2791


ATOM
2668
OG
SER
386
17.424
8.118
46.036
1.00
38.61

1DLC
2792


ATOM
2669
N
GLU
387
19.862
7.730
47.857
1.00
39.62

1DLC
2793


ATOM
2670
CA
GLU
387
21.067
6.957
47.593
1.00
38.96

1DLC
2794


ATOM
2671
C
GLU
387
22.112
7.171
46.694
1.00
37.55

1DLC
2795


ATOM
2672
O
GLU
387
21.908
7.960
49.618
1.00
37.34

1DLC
2796


ATOM
2673
CB
GLU
387
21.653
7.387
46.250
1.00
41.28

1DLC
2797


ATOM
2674
CG
GLU
387
20.667
7.310
45.114
1.00
48.83

1DLC
2798


ATOM
2675
CD
GLU
387
19.985
5.962
45.046
1.00
54.03

1DLC
2799


ATOM
2676
OE1
GLU
387
20.706
4.937
45.061
1.00
55.83

1DLC
2800


ATOM
2677
OE2
GLU
367
18.732
5.928
44.997
1.00
55.98

1DLC
2801


ATOM
2578
N
PRO
388
23.230
6.438
48.632
1.00
36.30

1DLC
2802


ATOM
2679
CA
PRO
388
24.279
6.593
49.645
1.00
35.40

1DLC
2803


ATOM
2680
C
PRO
388
24.950
7.981
49.642
1.00
34.68

1DLC
2804


ATOM
2681
O
PRO
388
25.396
8.486
48.603
1.00
33.48

1DLC
2805


ATOM
2682
CB
PRO
368
25.278
5.503
49.261
1.00
35.55

1DLC
2806


ATOM
2683
CG
PRO
388
24.406
4.448
48.677
1.00
36.31

1DLC
2807


ATOM
2684
CD
PRO
388
23.481
5.245
47.804
1.00
35.19

1DLC
2806


ATOM
2685
N
VAL
389
25.025
8.573
50.826
1.00
31.70

1DLC
2809


ATOM
2686
CA
VAL
389
25.640
9.878
51.034
1.00
33.25

1DLC
2810


ATOM
2687
C
VAL
389
27.136
9.922
50.661
1.00
34.25

1DLC
2811


ATOM
2688
O
VAL
389
27.852
8.928
50.800
1.00
35.26

1DLC
2812


ATOM
2669
CR
VAL
389
25.459
10.293
52.516
1.00
31.82

1DLC
2813


ATOM
2690
CG1
VAL
389
26.378
11.431
52.887
1.00
34.96

1DLC
2814


ATOM
2691
CG2
VAL
389
24.021
10.687
52.761
1.00
34.70

1DLC
2815


ATOM
2692
N
GLN
390
27.589
11.069
50.159
1.00
34.02

1DLC
2816


ATOM
2693
CA
GLN
390
28.994
11.268
49.798
1.00
34.03

1DLC
2817


ATOM
2694
C
GLN
390
29.556
12.458
50.567
1.00
34.97

1DLC
2818


ATOM
2695
O
GLN
390
28.929
13.511
50.642
1.00
37.45

1DLC
2819


ATOM
2696
CB
GLN
390
29.156
11.502
48.298
1.00
30.86

1DLC
2820


ATOM
2697
CG
GLN
390
28.968
10.258
47.478
1.00
34.90

1DLC
2821


ATOM
2698
CD
GLN
390
28.993
10.520
45.985
1.00
37.84

1DLC
2822


ATOM
2699
OE1
GLN
390
29.887
11.189
45.467
1.00
39.97

1DLC
2823


ATOM
2700
NE2
GLN
390
28.011
9.982
45.282
1.00
36.71

1DLC
2824


ATOM
2701
N
ASN
391
30.735
12.285
51.150
1.00
36.13

1DLC
2825


ATOM
2702
CA
ASN
391
31.364
13.350
51.918
1.00
35.90

1DLC
2826


ATOM
2703
C
ASN
391
32.749
13.684
51.399
1.00
34.56

1DLC
2827


ATOM
2704
O
ASN
391
33.668
12.796
51.197
1.00
35.19

1DLC
2828


ATOM
2705
CB
ASN
391
31.471
12.951
53.389
1.00
38.72

1DLC
2829


ATOM
2706
CO
ASN
391
30.122
12.680
54.021
1.00
46.12

1DLC
2830


ATOM
2707
OD1
ASN
391
29.101
13.193
53.576
1.00
54.69

1DLC
2831


ATOM
2708
ND2
ASN
391
30.108
11.871
55.065
1.00
48.42

1DLC
2832


ATOM
2709
N
LEU
392
32.992
14.965
51.149
1.00
35.38

1DLC
2833


ATOM
2710
CA
LEU
392
34.302
15.428
50.690
1.00
31.94

1DLC
2834


ATOM
2711
C
LEO
392
34.846
16.361
51.758
1.00
32.63

1DLC
2835


ATOM
2712
O
LEU
392
34.106
17.196
52.280
1.00
35.13

1DLC
2816


ATOM
2713
CB
LEU
392
34.192
16.194
49.369
1.00
27.68

1DLC
2837


ATOM
2714
CO
LEU
392
33.624
15.448
48.164
1.00
26.82

1DLC
2838


ATOM
2715
CD1
LEU
392
33.756
16.283
46.906
1.00
26.78

1DLC
2839


ATOM
2716
CD2
LEU
392
34.365
14.155
47.987
1.00
29.40

1DLC
2840


ATOM
2717
N
GLU
393
36.098
16.162
52.157
1.00
34.76

1DLC
2841


ATOM
2718
CA
GLU
393
36.721
17.039
53.150
1.00
34.99

1DLC
2842


ATOM
2.719
C
GLU
393
37.754
17.931
52.477
1.00
33.60

1DLC
2843


ATOM
2720
O
GLU
393
38.398
17.522
51.510
1.00
27.84

1DLC
2844


ATOM
2721
C8
GLU
393
37.371
16.246
54.273
1.00
41.28

1DLC
2845


ATOM
2722
CG
GLU
393
36.404
15.790
55.338
1.00
49.72

1DLC
2846


ATOM
2723
CD
GLU
393
36.135
14.297
55.306
1.00
57.23

1DLC
2847


ATOM
2724
OE1
GLU
393
36.653
13.603
54.396
1.00
62.82

1DLC
2848


ATOM
2725
OE2
GLU
393
35.401
13.814
56.200
1.00
61.57

1DLC
2849


ATOM
2726
N
PRE
394
37.912
19.148
52.989
1.00
35.60

1DLC
2850


ATOM
2727
CA
PHE
394
38.851
20.104
52.393
1.00
37.09

1DLC
2851


ATOM
2728
C
PHE
394
39.931
20.691
53.302
1.00
41.43

1DLC
2852


ATOM
2729
O
PRE
394
40.735
21.489
52.847
1.00
42.91

1DLC
2853


ATOM
2730
CB
PHE
394
38.069
21.238
51.721
1.00
29.33

1DLC
2854


ATOM
2731
CG
PHE
394
37.104
20.756
50.682
1.00
28.27

1DLC
2855


ATOM
2732
CD1
PHE
394
37.521
20.549
49.369
1.00
26.99

1DLC
2856


ATOM
2733
CD2
PHE
394
35.792
20.448
51.021
1.00
26.84

1DLC
2857


ATOM
2734
CE1
PRE
394
36.648
20.037
48.411
1.00
24.88

1DLC
2858


ATOM
2735
CE2
PHE
394
34.911
19.935
50.067
1.00
26.52

1DLC
2859


ATOM
2736
CZ 
PHE
394
35.342
19.730
48.760
1.00
25.09

1DLC
2860


ATOM
2737
N
ASN
395
39.973
20.256
54.561
1.00
45.12

1DLC
2861


ATOM
2738
CA
ASN
395
40.939
20.741
55.563
1.00
51.55

1DLC
2862


ATOM
2739
C
ASN 
395
42.208
21.432
55.023
1.00
53.27

1DLC
2863


ATOM
2740
O
ASN 
395
43.197
20.769
54.699
1.00
57.04

1DLC
2064


ATOM
2741
CB
ASN
395
41.358
19.590
56.489
1.00
57.57

1DLC
2865


ATOM
2742
CG
AN
395
40.201
18.671
56.848
1.00
64.16

1DLC
2866


ATOM
2743
OD1
ASN
395
39.360
19.002
57.684
1.00
69.45

1DLC
2067


ATOM
2744
ND2
AGN 
395
40.144
17.516
56.202
1.00
66.55

1DLC
2868


ATOM
2745
N
GLY
396
42.167
22.756
54.897
1.00
52.24

1DLC
2869


ATOM
2746
CA
GLY
396
43.331
23.488
54.409
1.00
52.60

1DLC
2870


ATOM
2747
C
GLY
396
43.473
23.670
52.898
1.00
51.64

1DLC
2871


ATOM
2748
O
GLY 
396
44.241
24.524
52.432
1.00
55.32

1DLC
2872


ATOM
2749
N
GLU 
397
42.812
22.805
52.137
1.00
46.45

1DLC
2873


ATOM
2750
CA
GLU
397
42.820
22.863
50.681
1.00
40.85

1DLC
2874


ATOM
2751
C
GLU 
397
42.048
24.096
50.190
1.00
36.96

1DLC
2875


ATOM
2752
O
GLU 
397
41.064
24.510
50.801
1.00
36.76

1DLC
2876


ATOM
2753
CB
GLU
397
42.132
21.628
50.108
1.00
42.90

1DLC
2877


ATOM
2754
CG
GLU 
397
42.655
20.311
50.629
1.00
46.38

1DLC
2878


ATOM
2755
CD
GLU 
397
44.049
19.997
50.125
1.00
50.24

1DLC
2879


ATOM
2756
OE1
GLU 
397
44.319
20.217
48.920
1.00
48.15

1DLC
2880


ATOM
2757
OE2
GLU 
397
44.873
19.519
50.939
1.00
54.59

1DLC
2881


ATOM
2758
N
LYS
398
42.486
24.677
49.084
1.00
32.97

1DLC
2882


ATOM
2759
CA
LYS
398
41.793
25.819
48.515
1.00
29.53

1DLC
2883


ATOM
2760
C
LYS 
398
41.153
25.405
47.194
1.00
28.78

1DLC
2884


ATOM
2751
O
LYS 
398
41.874
25.081
46.234
1.00
28.04

1DLC
2885


ATOM
2762
CB
LYS
398
42.749
26.983
48.303
1.00
30.66

1DLC
2886


ATOM
2763
CG
LYS
398
43.278
27.560
49.591
1.00
36.26

1DLC
2887


ATOM
2764
CD
LYS 
398
44.378
28.545
49.306
1.00
42.44

1DLC
2088


ATOM
2765
CE
LYS 
398
44.979
29.085
50.580
1.00
44.63

1DLC
2089


ATOM
2766
NZ
LYS 
398
46.179
29.912
50.258
1.00
52.09

1DLC
2890


ATOM
2767
N
VAL 
399
39.830
25.374
47.162
1.00
25.99

1DLC
2891


ATOM
2768
CA
VAL
399
39.097
24.992
45.960
1.00
22.58

1DLC
2892


ATOM
2769
C
VAL 
399
39.068
26.170
45.001
1.00
20.61

1DLC
2893


ATOM
2770
O
VAL 
399
38.400
27.169
45.238
1.00
22.09

1DLC
2894


ATOM
2771
CB
VAL
399
37.663
24.509
46.293
1.00
24.43

1DLC
2895


ATOM
2772
CG1
VAL
399
36.933
24.069
45.021
1.00
21.92

1DLC
2896


ATOM
2773
CG2
VAL 
399
37.726
23.355
47.281
1.00
22.57

1DLC
2897


ATOM
2774
N
TYR 
400
39.840
26.057
43.931
1.00
19.64

1DLC
2898


ATOM
2775
CA
TYR
400
39.937
27.125
42.952
1.00
18.79

1DLC
2899


ATOM
2776
C
TYR 
400
39.132
26.805
41.684
1.00
20.30

1DLC
2900


ATOM
2777
O
TYR 
400
39.118
27.714
40.769
1.00
15.31

1DLC
2901


ATOM
2778
CB
TYR
400
41.408
27.404
42.624
1.00
19.27

1DLC
2902


ATOM
2779
CG
TYR 
400
42.148
26.253
42.000
1.00
16.63

1DLC
2903


ATOM
2780
CD1
TYR 
400
42.774
25.290
42.791
1.00
16.65

1DLC
2904


ATOM
2781
CD2
TYR
400
42.234
26.134
40.616
1.00
18.17

1DLC
2905


ATOM
2782
CE1
TYR 
400
43.477
24.226
42.215
1.00
19.68

1DLC
2906


ATOM
2783
CE2
TYR 
400
42.929
25.080
40.026
1.00
23.20

1DLC
2907


ATOM
2784
CZ 
TYR 
400
43.549
24.127
40.830
1.00
21.51

1DLC
2908


ATOM
2785
OH
TYR 
400
44.227
23.084
40.235
1.00
22.85

1DLC
2909


ATOM
2786
N
ARG 
401
38.461
25.742
41.632
1.00
20.95

1DLC
2910


ATOM
2787
CA
ARG
401
37.640
25.419
40.484
1.00
21.84

1DLC
2911


ATOM
2788
C
ARG 
401
36.590
24.354
40.770
1.00
23.36

1DLC
2912


ATOM
2789
O
ARG 
401
36.748
23.510
41.658
1.00
24.04

1DLC
2913


ATOM
2790
CB
ARG
401
38.508
24.984
39.312
1.00
24.53

1DLC
2914


ATOM
2791
CG
ARG 
401
37.822
25.117
37.966
1.00
24.58

1DLC
2915


ATOM
2792
CD
ARG 
401
38.656
24.464
36.894
1.00
25.33

1DLC
2916


ATOM
2793
NE
ARG 
401
38.195
24.815
35.558
1.00
29.66

1DLC
2917


ATOM
2794
CZ
ARG 
401
38.722
24.326
34.444
1.00
28.89

1DLC
2918


ATOM
2795
NH1
ARG 
401
39.724
23.463
34.506
1.00
35.25

1DLC
2919


ATOM
2796
NH2
ARG
401
38.273
24.723
33.268
1.00
27.33

1DLC
2920


ATOM
2797
N
ALA
402
35.4922
4.450
40.035
1.00
21.33

1DLC
2921


ATOM
2798
CA
ALA
402
34.384
23.514
40.135
1.00
21.93

1DLC
2922


ATOM
2799
C
ALA
402
33.763
23.383
38.747
1.00
23.71

1DLC
2923


ATOM
2800
O
ALA
402
33.400
24.385
38.116
1.00
27.23

1DLC
2924


ATOM
2801
CB
ALA
402
33.358
24.003
41.137
1.00
21.05

1DLC
2925


ATOM
2802
N
VAL
403
33.751
22.164
38.225
1.00
23.23

1DLC
2926


ATOM
2803
CA
VAL
403
33.173
21.907
36.910
1.00
24.12

1DLC
2927


ATOM
2604
C
VAL
403
32.056
20.674
37.081
1.00
25.85

1DLC
2928


ATOM
2805
O
VAL
403
32.241
19.841
37.747
1.00
26.19

1DLC
2929


ATOM
2806
CB
VAL
403
34.235
21.401
35.916
1.00
23.95

1DLC
2930


ATOM
2807
CG1
VAL
403
33.631
21.290
34.525
1.00
19.01

1DLC
2931


ATOM
2808
CG2
VAL
403
35.440
22.342
35.910
1.00
23.88

1DLC
2932


ATOM
2809
N
ALA
404
30.902
21.146
36.478
1.00
23.02

1DLC
2933


ATOM
2810
CA
ALA
404
29.754
20.263
36.631
1.00
19.31

1DLC
2934


ATOM
2811
C
ALA
404
29.100
19.659
35.390
1.00
18.96

1DLC
2935


ATOM
2812
O
ALA
404
29.104
20.236
34.299
1.00
19.34

1DLC
2936


ATOM
2813
CB
ALA
404
28.697
20.966
37.477
1.00
17.73

1DLC
2937


ATOM
2814
N
ASN
405
28.526
18.480
35.596
1.00
19.71

1DLC
2938


ATOM
2815
CA
ASN
405
27.792
17.748
34.574
1.00
21.57

1DLC
2939


ATOM
2816
C
ASN
405
26.322
17.840
34.955
1.00
21.86

1DLC
2940


ATOM
2817
O
ASN
405
25.963
17.847
36.143
1.00
20.98

1DLC
2941


ATOM
2818
CB
ASN
405
28.151
16.256
34.582
1.00
24.99

1DLC
2942


ATOM
2819
CG
ASN
405
29.564
15.985
34.146
1.00
28.98

1DLC
2943


ATOM
2820
OD1
ASN
405
30.513
16.496
34.730
1.00
36.18

1DLC
2944


ATOM
2821
ND2
ASN
405
29.720
15.150
33.136
1.00
28.22

1DLC
2945


ATOM
2822
N
THR
406
25.463
17.927
33.957
1.00
21.73

1DLC
2946


ATOM
2823
CA
THR
406
24.032
17.947
34.231
1.00
25.13

1DLC
2947


ATOM
2824
C
THR
406
23.374
16.983
33.257
1.00
26.31

1DLC
2948


ATOM
2825
O
THR
406
23.974
16.607
32.242
1.00
26.28

1DLC
2949


ATOM
2826
CR
THR
406
23.390
19.362
34.089
1.00
24.14

1DLC
2950


ATOM
2827
OG1
THR
406
23.651
19.889
32.785
1.00
25.97

1DLC
2951


ATOM
2828
CG2
THR
406
23.911
20.324
35.163
1.00
20.04

1DLC
2952


ATOM
2829
N
ASN
407
22.185
16.509
33.603
1.00
27.43

1DLC
2953


ATOM
2830
CA
ASN
407
21.474
15.608
32.706
1.00
27.11

1DLC
2954


ATOM
2831
C
ASN
407
19.98
115.902
32.722
1.00
25.60

1DLC
2955


ATOM
2832
O
ASN
407
19.478
16.551
33.637
1.00
24.05

1DLC
2956


ATOM
2833
CB
ASN
407
21.750
14.141
33.059
1.00
25.28

1DLC
2957


ATOM
2834
CO
ANN
407
21.683
13.226
31.842
1.00
22.24

1DLC
2958


ATOM
2835
OD1
ASN
407
21.389
13.665
30.730
1.00
19.56

1DLC
2959


ATOM
2836
ND2
ASN
407
21.969
11.955
32.047
1.00
24.80

1DLC
2960


ATOM
2837
N
LEO
408
19.281
15.447
31.692
1.00
25.59

1DLC
2961


ATOM
2838
CA
LEU
408
17.852
15.673
31.604
1.00
27.24

1DLC
2962


ATOM
2839
C
LEU
408
17.090
14.488
31.024
1.00
27.97

1DLC
2963


ATOM
2640
O
LEU
408
17.607
13.731
30.205
1.00
29.46

1DLC
2564


ATOM
2841
CB
LEO
408
17.561
16.945
30.790
1.00
28.54

1DLC
2965


ATOM
2842
CO
LEU
408
17.883
17.006
29.289
1.00
28.16

1DLC
2966


ATOM
2843
CD1
LEU
408
16.710
16.462
28.507
1.00
31.12

1DLC
2967


ATOM
2844
CD2
LEO
408
18.137
18.439
28.859
1.00
25.06

1DLC
2968


ATOM
2845
N
ALA
409
15.863
14.319
31.489
1.00
27.95

1DLC
2969


ATOM
2846
CA
ALA
409
14.990
13.263
31.011
1.00
26.71

1DLC
2970


ATOM
2847
C
ALA
409
13.750
13.974
30.501
1.00
26.39

1DLC
2971


ATOM
2648
O
ALA
409
13.185
14.819
31.197
1.00
27.94

1DLC
2972


ATOM
2849
CB
ALA
409
14.628
12.317
32.145
1.00
25.33

1DLC
2973


ATOM
2850
N
VAL
410
13.376
13.701
29.259
1.00
26.74

1DLC
2974


ATOM
2851
CA
VAL
410
12.189
14.312
28.670
1.00
27.20

1DLC
2975


ATOM
2852
C
VAL
410
10.956
13.404
28.802
1.00
28.76

1DLC
2976


ATOM
2853
O
VAL
410
10.885
12.345
28.179
1.00
31.07

1DLC
2977


ATOM
2854
CB
VAL
410
12.419
14.650
27.183
1.00
27.70

1DLC
2978


ATOM
2855
CG1
VAL
410
11.1621
5.238
26.567
1.00
25.34

1DLC
2979


ATOM
2856
CG2
VAL
410
13.561
15.627
27.050
1.00
28.45

1DLC
2980


ATOM
2857
N
TRP
411
10.027
13.792
29.669
1.00
28.92

1DLC
2981


ATOM
2858
CA
TRP
411
8.787
13.047
29.871
1.00
32.40

1DLC
2982


ATOM
2859
C
TRP
411
7.681
13.644
28.982
1.00
36.76

1DLC
2983


ATOM
2860
O
TRP
411
7.783
14.797
28.558
1.00
31.48

1DLC
2984


ATOM
2861
CB
TRP
411
8.374
13.087
31.341
1.00
30.13

1DLC
2985


ATOM
2862
CG
TRP
411
9.146
12.153
32.224
1.00
31.99

1DLC
2986


ATOM
2863
CD1
TRP
411
10.500
12.010
32.283
1.00
32.36

1DLC
2987


ATOM
2864
CD2
TRP
411
8.609
11.291
33.237
1.00
33.30

1DLC
2988


ATOM
2865
NE1
TRP
411
10.841
11.127
33.274
1.00
31.66

1DLC
2989


ATOM
2866
CE2
TRP
411
9.700
10.671
33.878
1.00
34.52

1DLC
2990


ATOM
2867
CE3
TRP
411
7.310
10.988
33.670
1.00
33.48

1DLC
2991


ATOM
2868
CZ2
TRP
411
9.534
9.767
34.938
1.00
37.09

1DLC
2992


ATOM
2869
CZ3
TRP
411
7.146
10.089
34.725
1.00
33.78

1DLC
2993


ATOM
2870
CH2
TRP
411
8.253
9.492
35.345
1.00
33.59

1DLC
2994


ATOM
2871
N
PRO
412
6.574
12.900
28.755
1.00
41.54

1DLC
2995


ATOM
2872
CA
PRO
412
5.451
13.348
27.917
1.00
41.87

1DLC
2996


ATOM
2873
C
PRO
412
4.993
14.776
28.158
1.00
43.64

1DLC
2997


ATOM
2874
O
PRO
412
4.725
15.517
27.218
1.00
46.92

1DLC
2998


ATOM
2875
CB
PRO
412
4.349
12.361
28.277
1.00
39.76

1DLC
2999


ATOM
2876
CG
PRO
412
5.098
11.130
28.537
1.00
42.46

1DLC
3000


ATOM
2877
CD
PRO
412
6.231
11.620
29.399
1.00
41.84

1DLC
3001


ATOM
2878
N
SER
413
4.901
15.157
29.421
1.00
45.10

1DLC
3002


ATOM
2879
CA
SER
413
4.460
16.501
29.764
1.00
49.60

1DLC
3003


ATOM
2880
C
SER
413
5.322
17.110
30.873
1.00
49.62

1DLC
3004


ATOM
2881
O
SER
413
4.843
17.900
31.695
1.00
51.51

1DLC
3005


ATOM
2882
CB
SER
413
2.998
16.446
30.199
1.00
51.77

1DLC
3006


ATOM
2883
OG
SER
413
2.797
15.328
31.045
1.00
57.37

1DLC
3007


ATOM
2884
N
ALA
414
6.607
16.764
30.865
1.00
45.33

1DLC
3008


ATOM
2885
CA
ALA
414
7.534
17.257
31.871
1.00
38.96

1DLC
3009


ATOM
2886
C
ALA
414
8.979
16.981
31.485
1.00
36.86

1DLC
3010


ATOM
2887
O
ALA
414
9.275
16.041
30.750
1.00
36.90

1DLC
3011


ATOM
2888
CR
ALA
414
7.227
16.613
33.222
1.00
36.07

1DLC
3012


ATOM
2889
N
VAL
415
9.874
17.834
31.959
1.00
31.55

1DLC
3013


ATOM
2890
CA
VAL
415
11.294
17.667
31.713
1.00
28.69

1DLC
3014


ATOM
2891
C
VAL
415
11.957
17.736
33.083
1.00
27.90

1DLC
3015


ATOM
2892
O
VAL
415
11.636
18.604
33.895
1.00
28.78

1DLC
3016


ATOM
2893
CR 
VAL
415
11.850
18.764
30.770
1.00
26.51

1DLC
3017


ATOM
2894
CG1
VAL
415
13.373
18.595
30.699
1.00
27.88

1DLC
3018


ATOM
2895
CG2
VAL
415
11.272
18.594
29.379
1.00
24.80

1DLC
3019


ATOM
2896
N
TYR
416
12.806
16.760
33.372
1.00
25.67

1DLC
3020


ATOM
2897
CA
TYR
416
13.504
16.713
34.648
1.00
26.02

1DLC
3021


ATOM
2898
C
TYR
416
14.992
16.821
34.407
1.00
26.24

1DLC
3022


ATOM
2899
O
TYR
416
15.537
16.120
33.560
1.00
28.40

1DLC
3023


ATOM
2900
CA
TYR
416
13.209
15.399
35.366
1.00
26.73

1DLC
3024


ATOM
2901
CG
TYR
416
11.746
15.180
35.657
1.00
29.24

1DLC
3025


ATOM
2902
CD1
TYR
416
10.910
14.571
34.720
1.00
30.70

1DLC
3026


ATOM
2903
CD2
TYR
416
11.194
15.583
36.669
1.00
26.65

1DLC
3027


ATOM
2904
CE1
TYR
416
9.567
14.373
34.985
1.00
30.31

1DLC
3028


ATOM
2905
CE2
TYR
416
9.857
15.387
37.144
1.00
31.22

1DLC
3029


ATOM
2906
CZ 
TYR
416
9.049
14.784
36.200
1.00
32.49

1DLC
3030


ATOM
2907
OH
TYR
416
7.716
14.603
36.473
1.00
38.69

1DLC
3031


ATOM
2908
N
SER
417
15.650
17.706
35.138
1.00
27.76

1DLC
3032


ATOM
2909
CA
SER
417
17.090
17.863
34.986
1.00
28.62

1DLC
3033


ATOM
2910
C
SER
417
17.796
18.114
36.319
1.00
28.34

1DLC
3034


ATOM
2911
O
SER
417
17.236
18.706
37.242
1.00
27.52

1DLC
3035


ATOM
2912
CO 
SER
417
17.403
19.015
34.003
1.00
26.02

1DLC
3036


ATOM
2913
OG 
SER
417
16.714
20.196
34.351
1.00
31.53

1DLC
3037


ATOM
2914
N
GLY
418
19.016
17.602
36.430
1.00
28.56

1DLC
3038


ATOM
2915
CA
GLY
418
19.765
17.766
37.660
1.00
27.48

1DLC
3039


ATOM
2916
C
GLY 
418
21.269
17.710
37.478
1.00
27.67

1DLC
3040


ATOM
2917
O
GLY 
418
21.769
17.358
36.397
1.00
26.87

1DLC
3041


ATOM
2918
N
VAL 
419
21.984
18.098
38.532
1.00
27.26

1DLC
3042


ATOM
2919
CA
VAL
419
23.446
18.087
38.551
1.00
23.88

1DLC
3043


ATOM
2920
C
VAL 
419
23.883
16.673
38.946
1.00
24.66

1DLC
3044


ATOM
2921
O
VAL 
419
23.612
16.192
40.047
1.00
23.69

1DLC
3045


ATOM
2922
CB
VAL 
419
23.992
19.146
39.531
1.00
22.05

1DLC
3046


ATOM
2923
CG1
VAL 
419
25.513
19.176
39.492
1.00
20.25

1DLC
3047


ATOM
2924
CG2
VAL
419
23.424
20.511
39.171
1.00
19.09

1DLC
3048


ATOM
2925
N
THE 
420
24.552
16.006
38.022
1.00
24.57

1DLC
3049


ATOM
2926
CA
THR 
420
24.965
14.628
38.227
1.00
26.41

1DLC
3050


ATOM
2927
C
THR 
420
26.407
14.410
38.671
1.00
29.16

1DLC
3051


ATOM
2928
O
THE 
420
26.720
13.410
39.323
1.00
30.90

1DLC
3052


ATOM
2929
CB
THR 
420
24.781
13.874
36.938
1.00
26.62

1DLC
3053


ATOM
2930
OG1
THR 
420
25.586
14.506
35.944
1.00
28.39

1DLC
3054


ATOM
2931
CG2
THR 
420
23.329
13.938
36.484
1.00
27.96

1DLC
3055


ATOM
2932
N
LYS 
421
27.292
15.325
38.295
1.00
31.11

1DLC
3056


ATOM
2933
CA
LYS 
421
28.704
15.194
38.646
1.00
30.22

1DLC
3057


ATOM
2934
C
LYS 
421
29.363
16.550
38.868
1.00
28.76

1DLC
3058


ATOM
2935
O
LYS 
421
29.099
17.506
38.138
1.00
26.51

1DLC
3059


ATOM
2936
CB
LYS 
421
29.433
14.443
37.526
1.00
29.98

1DLC
3060


ATOM
2937
CG
LYS 
421
30.858
14.012
37.820
1.00
29.15

1DLC
3061


ATOM
2538
CD
LYS 
421
31.539
13.708
36.499
1.00
33.33

1DLC
3062


ATOM
2939
CE
LYS 
421
33.002
13.320
36.640
1.00
36.06

1DLC
3063


ATOM
2940
NZ
LYS 
421
33.195
11.871
36.934
1.00
44.02

1DLC
3064


ATOM
2941
N
VAL 
422
30.191
16.637
39.904
1.00
28.39

1DLC
3065


ATOM
2942
CA
VAL
422
30.912
17.872
40.208
1.00
28.83

1DLC
3066


ATOM
2943
C
VAL 
422
32.374
17.589
40.571
1.00
28.74

1DLC
3067


ATOM
2944
O
VAL 
422
32.679
16.920
41.562
1.00
24.14

1DLC
3068


ATOM
2945
CB
VAT
422
30.269
18.688
41.364
1.00
28.45

1DLC
3069


ATOM
2946
CG1
VAL
422
30.903
20.084
41.428
1.00
26.59

1DLC
3070


ATOM
2947
CG2
VAL
422
28.760
18.792
41.187
1.00
26.33

1DLC
3071


ATOM
2948
N
GLU 
423
33.277
18.111
39.756
1.00
30.40

1DLC
3072


ATOM
2949
CA
GLU
423
34.697
17.934
39.988
1.00
32.36

1DLC
3071


ATOM
2950
C
GLU 
423
35.337
19.193
40.577
1.00
30.72

1DLC
3074


ATOM
2951
O
GLU 
423
35.353
20.255
39.952
1.00
29.33

1DLC
3075


ATOM
2952
CR 
CLU
423
35.365
17.560
38.684
1.00
35.60

1DLC
3076


ATOM
2953
CG
GLU
423
36.857
17.283
38.819
1.00
46.42

1DLC
3077


ATOM
2954
CD
GLU 
423
37.401
16.588
37.596
1.00
54.46

1DLC
3078


ATOM
2955
OE1
GLU
423
37.241
15.348
37.502
1.00
59.71

1DLC
3079


ATOM
2956
OE2
GLU
423
37.964
17.283
36.720
1.00
58.05

1DLC
3080


ATOM
2957
N
PHE
424
35.833
19.066
41.797
1.00
28.13

1DLC
3081


ATOM
2958
CA
PHE
424
36.491
20.167
42.486
1.00
29.49

1DLC
3082


ATOM
2959
C
PHE
424
38.029
20.130
42.355
1.00
30.85

1DLC
3083


ATOM
2960
O
PHE
424
38.672
19.105
42.628
1.00
30.79

1DLC
3084


ATOM
2961
CB
PHE
424
36.134
20.139
43.975
1.00
29.46

1DLC
3085


ATOM
2962
CG
PHE
424
34.662
20.205
44.253
1.00
30.25

1DLC
3086


ATOM
2963
CD1
PHE
424
34.019
21.434
44.378
1.00
29.50

1DLC
3087


ATOM
2964
CD2
PHE
424
33.923
19.043
44.422
1.00
29.43

1DLC
3088


ATOM
2965
CE1
PHE
424
32.668
21.504
44.670
1.00
27.70

1DLC
3089


ATOM
2966
CE2
PHE
424
32.572
19.100
44.714
1.00
29.35

1DLC
3090


ATOM
2967
CZ
PHE
424
31.942
20.336
44.840
1.00
30.09

1DLC
3091


ATOM
2968
N
SER 
425
38.613
21.249
41.937
1.00
29.43

1DLC
3092


ATOM
2969
CA
SER
425
40.065
21.361
41.830
1.00
25.64

1DLC
3093


ATOM
2970
C
SER 
425
40.569
22.074
43.080
1.00
27.43

1DLC
3094


ATOM
2971
O
SER 
425
40.136
23.184
43.390
1.00
27.70

1DLC
3095


ATOM
2972
CR
SER
425
40.469
22.167
40.603
1.00
24.73

1DLC
3096


ATOM
2973
OG 
SER 
425
40.202
21.458
39.410
1.00
27.45

1DLC
3097


ATOM
2974
N
GLN 
426
41.459
21.428
43.815
1.00
29.40

1DLC
3098


ATOM
2975
CA
GLN
426
42.010
22.018
45.028
1.00
34.28

1DLC
3099


ATOM
2976
C
GLN
426
43.541
22.162
45.029
1.00
37.43

1DLC
3100


ATOM
2977
O
GLN
426
44.257
21.428
44.344
1.00
38.20

1DLC
3101


ATOM
2978
CS 
GLN
426
41.548
21.225
46.251
1.00
32.26

1DLC
3102


ATOM
2979
CG
GLN
426
41.830
19.736
46.179
1.00
33.97

1DLC
3103


ATOM
2980
CD
GLN
426
41.196
18.983
47.329
1.00
37.54

1DLC
3104


ATOM
2981
OE1
GLN
426
40.063
19.258
47.714
1.00
39.93

1DLC
3105


ATOM
2992
NE2
GLN 
426
41.919
18.028
47.884
1.00
37.39

1DLC
3106


ATOM
2983
N
TYR
427
44.026
23.163
45.754
1.00
40.45

1DLC
3107


ATOM
2984
CA
TYR
427
45.455
23.402
45.872
1.00
41.55

1DLC
3108


ATOM
2985
C
TYR
427
45.819
23.459
47.351
1.00
42.39

1DLC
3109


ATOM
2986
O
TYR
427
45.118
24.072
48.149
1.00
40.82

1DLC
3110


ATOM
2987
CB
TYR
427
45.846
24.713
45.186
1.00
44.27

1DLC
3111


ATOM
2988
CG
TYR
427
47.328
25.006
45.252
1.00
49.58

1DLC
3112


ATOM
2989
CD1
TYR 
427
48.219
24.383
44.377
1.00
51.96

1DLC
3113


ATOM
2990
CD2
TYR 
427
47.848
25.883
46.209
1.00
49.78

1DLC
3114


ATOM
2991
CE1
TYR 
427
49.589
24.622
44.448
1.00
52.52

1DLC
3115


ATOM
2992
CE2
TYR 
427
49.218
26.128
46.292
1.00
52.70

1DLC
3116


ATOM
2993
CZ
TYR
427
50.083
25.493
45.408
1.00
53.61

1DLC
3117


ATOM
2994
OH 
TYR
427
51.440
25.726
45.482
1.00
54.14

1DLC
3118


ATOM
2995
N
ASN
428
46.883
22.761
47.721
1.00
47.81

1DLC
3119


ATOM
2996
CA
ASN
428
47.350
22.743
49.104
1.00
51.08

1DLC
3120


ATOM
2997
C
ASN
428
48.569
23.666
49.205
1.00
54.49

1DLC
3121


ATOM
2998
O
ASN
428
49.669
23.296
48.790
1.00
55.38

1DLC
3122


ATOM
2999
CB
ASN
428
47.724
21.313
49.504
1.00
49.62

1DLC
3123


ATOM
3000
CG
ASN
428
48.045
21.180
50.977
1.00
49.60

1DLC
3124


ATOM
3001
OD1
ASN 
428
48.565
22.103
51.600
1.00
50.02

1DLC
3125


ATOM
3002
ND2
ASN
428
47.762
20.021
51.536
1.00
51.27

1DLC
3126


ATOM
3003
N
ASP
429
48.365
24.871
49.732
1.00
57.69

1DLC
3127


ATOM
3004
CA
ASP
429
49.447
25.851
49.868
1.00
61.09

1DLC
1128


ATOM
3005
C
ASP
429
50.553
25.433
50.846
1.00
61.35

1DLC
3129


ATOM
3006
O
ASP
429
51.663
25.955
50.798
1.00
60.38

1DLC
3130


ATOM
3007
CE
ASP
429
48.884
27.234
50.231
1.00
63.50

1DLC
3131


ATOM
3008
CG
ASP
429
48.083
27.225
51.521
1.00
69.23

1DLC
3132


ATOM
3009
OD1
ASP 
429
47.071
26.486
51.596
1.00
74.87

1DLC
3133


ATOM
3010
OD2
ASP 
429
48.462
27.960
52.463
1.00
69.36

1DLC
3134


ATOM
3011
N
GLN
430
50.246
24.488
51.729
1.00
63.12

1DLC
3135


ATOM
3012
CA
GLN
430
51.221
23.987
52.688
1.00
64.06

1DLC
3136


ATOM
3013
C
GLN
430
52.185
23.064
51.938
1.00
60.99

1DLC
3137


ATOM
3014
O
GLN
430
53.368
23.353
51.802
1.00
62.46

1DLC
3138


ATOM
3015
CB
GLN
430
50.543
23.202
53.817
1.00
68.60

1DLC
3139


ATOM
3016
CG
GLN
430
49.735
24.035
54.821
1.00
77.24

1DLC
3140


ATOM
3017
CD
GLN
430
48.372
24.495
54.295
1.00
83.08

1DLC
3141


ATOM
3018
OE1
GLN 
430
48.121
25.694
54.164
1.00
86.17

1DLC
3142


ATOM
3019
NE2
GLN 
430
47.483
23.546
54.020
1.00
82.81

1DLC
3143


ATOM
3020
N
THR
431
51.643
21.973
51.409
1.00
57.70

1DLC
3144


ATOM
3021
CA
THR
431
52.425
20.992
50.658
1.00
54.67

1DLC
3145


ATOM
3022
C
THR
431
52.553
21.360
49.179
1.00
53.42

1DLC
3146


ATOM
3023
O
THR
431
52.775
20.505
48.334
1.00
52.29

1DLC
3147


ATOM
3024
CB
THR
431
51.786
19.594
50.760
1.00
54.43

1DLC
3148


ATOM
3025
OG1
THR
431
50.489
19.617
50.155
1.00
55.57

1DLC
3149


ATOM
3026
CG2
THR
431
51.627
19.188
52.223
1.00
54.20

1DLC
3150


ATOM
3027
N
ASP
432
52.399
22.643
48.883
1.00
55.66

1DLC
3151


ATOM
2028
CA
ASP
432
52.476
23.176
47.526
1.00
59.05

1DLC
3152


ATOM
3029
C
ASP
432
52.136
22.273
46.343
1.00
59.61

1DLC
3153


ATOM
3030
O
ASP
432
52.945
22.109
45.428
1.00
61.57

1DLC
3154


ATOM
3031
CB
ASP
432
53.816
23.875
47.288
1.00
63.68

1DLC
3155


ATOM
3032
CG
ASP
432
53.877
25.252
47.934
1.00
69.48

1DLC
3156


ATOM
3033
OD1
ASP 
432
53.439
26.238
47.293
1.00
70.82

1DLC
3157


ATOM
3034
OD2
ASP 
432
54.360
25.347
49.086
1.00
71.66

1DLC
3158


ATOM
3035
N
GLU
433
50.928
21.711
46.346
1.00
59.44

1DLC
3159


ATOM
3036
CA
GLU
433
50.480
20.871
45.233
1.00
57.29

1DLC
3160


ATOM
3037
C
GLU
433
48.957
20.787
45.047
1.00
52.84

1DLC
3161


ATOM
1038
O
GLU
433
48.178
20.915
45.994
1.00
46.51

1DLC
3162


ATOM
3039
CB
GLU
433
51.137
19.476
45.260
1.00
63.46

1DLC
3163


ATOM
3040
CG
GLU
433
50.290
18.331
45.795
1.00
69.79

1DLC
3164


ATOM
3041
CD
GLU
433
50.272
18.275
47.305
1.00
74.20

1DLC
3165


ATOM
3042
OE1
GLU
433
51.179
17.634
47.887
1.00
75.74

1DLC
3166


ATOM
3043
OE2
GLU
433
49.349
18.868
47.907
1.00
78.38

1DLC
3167


ATOM
3044
N
ALA
434
48.553
20.634
43.792
1.00
51.12

1DLC
3168


ATOM
3045
CA
ALA
434
47.146
20.552
43.419
1.00
50.02

1DLC
3169


ATOM
3046
C
ALA
434
46.636
19.113
43.301
1.00
48.51

1DLC
3170


ATOM
3047
O
ALA
434
47.418
18.168
43.249
1.00
51.46

1DLC
3171


ATOM
3048
CS 
ALA
434
46.913
21.302
42.107
1.00
49.76

1DLC
3172


ATOM
3049
N
SER
435
45.316
18.969
43.250
1.00
44.96

1DLC
3173


ATOM
3050
CA
SER
435
44.650
17.674
43.139
1.00
38.99

1DLC
3174


ATOM
3051
C
SER
435
43.159
17.914
42.940
1.00
39.56

1DLC
3175


ATOM
3052
O
SER
435
42.693
19.048
42.999
1.00
38.70

1DLC
3176


ATOM
3053
CB
SER
435
44.845
16.857
44.415
1.00
35.36

1DLC
3177


ATOM
3054
OG
SER
435
44.211
17.492
45.528
1.00
32.98

1DLC
3178


ATOM
3055
N
THR
436
42.407
16.847
42.705
1.00
38.68

1DLC
3179


ATOM
3056
CA
THR
436
40.967
16.979
42.526
1.00
36.86

1DLC
3180


ATOM
3057
C
THE
436
40.171
16.007
43.392
1.00
36.34

1DLC
3181


ATOM
3058
O
THR
436
40.679
14.970
43.823
1.00
37.73

1DLC
3182


ATOM
3059
CB
THE
436
40.540
16.757
41.065
1.00
35.68

1DLC
3183


ATOM
3060
OG1
THR
436
40.788
15.397
40.699
1.00
41.63

1DLC
3184


ATOM
3061
CG2
THE
436
41.313
17.674
40.110
1.00
37.09

1DLC
3185


ATOM
3062
N
GLN
437
38.947
16.407
43.713
1.00
35.55

1DLC
3186


ATOM
1081
CA
GLN
437
38.009
15.597
44.485
1.00
33.02

1DLC
3187


ATOM
3064
C
GLN
437
36.709
15.729
43.723
1.00
34.09

1DLC
3188


ATOM
3065
O
GLN
437
36.391
16.809
43.227
1.00
34.18

1DLC
3189


ATOM
3066
CB
GLN
437
37.813
16.140
45.894
1.00
30.43

1DLC
3190


ATOM
3067
CG
GLN
437
38.812
15.635
46.887
1.00
30.16

1DLC
3191


ATOM
3068
CD
GLN
437
38.380
15.896
48.305
1.00
12.10

1DLC
3192


ATOM
3069
OE1
GLN
437
37.962
14.984
49.015
1.00
36.80

1DLC
3193


ATOM
3070
NE2
GLN
437
38.458
17.144
48.726
1.00
34.86

1DLC
3194


ATOM
3071
N
THR
438
35.966
14.644
43.575
1.00
34.88

1DLC
3195


ATOM
3072
CA
THR
438
34.725
14.759
42.828
1.00
35.70

1DLC
3196


ATOM
3073
C
THE
438
33.533
14.042
43.417
1.00
34.07

1DLC
3197


ATOM
3074
O
THR
438
33.663
13.090
44.177
1.00
35.71

1DLC
3198


ATOM
3075
CB
THR
438
34.857
14.280
41.346
1.00
37.66

1DLC
3199


ATOM
3076
OG1
THE
438
34.466
12.905
41.251
1.00
37.09

1DLC
3200


ATOM
3077
CG2
THR
438
36.286
14.453
40.812
1.00
32.87

1DLC
3201


ATOM
3078
N
TYR
439
32.366
14.560
43.074
1.00
34.88

1DLC
3202


ATOM
3079
CA
TYR
439
31.100
13.988
43.473
1.00
32.18

1DLC
3203


ATOM
3080
C
TYR
439
30.575
13.313
42.197
1.00
32.47

1DLC
3204


ATOM
3081
O
TYR
439
30.636
13.888
41.102
1.00
30.88

1DLC
3205


ATOM
3082
CB
TYR
439
30.141
15.089
43.936
1.00
29.14

1DLC
3206


ATOM
3083
CO
TYR
439
28.691
14.683
43.824
1.00
30.66

1DLC
3207


ATOM
3084
CD1
TYR
439
28.126
13.796
44.732
1.00
28.98

1DLC
3208


ATOM
3085
CD2
TYR
439
27.902
15.117
42.751
1.00
27.98

1DLC
3209


ATOM
3086
CE1
TYR
439
26.825
13.344
44.588
1.00
29.00

1DLC
3210


ATOM
3087
CE2
TYR
439
26.598
14.667
42.595
1.00
26.79

1DLC
3211


ATOM
3088
CZ
TYR
439
26.072
13.778
43.518
1.00
25.85

1DLC
3212


ATOM
3089
OH
TYR
439
24.798
13.305
43.369
1.00
25.37

1DLC
3213


ATOM
3090
N
ASP
440
30.098
12.082
42.323
1.00
33.95

1DLC
3214


ATOM
3091
CA
ASP
440
29.568
11.366
41.162
1.00
36.24

1DLC
3215


ATOM
3092
C
ASP
440
28.231
10.735
41.551
1.00
37.15

1DLC
3216


ATOM
3093
O
ASP
440
28.152
10.014
42.547
1.00
37.73

1DLC
3217


ATOM
3094
CB
ASP
440
30.560
10.285
40.711
1.00
37.85

1DLC
3218


ATOM
3095
CG
ASP
440
30.332
9.831
39.277
1.00
40.56

1DLC
3219


ATOM
3096
OD1
ASP
440
29.253
9.284
38.575
1.00
45.14

1DLC
3220


ATOM
3097
OD2
ASP
440
31.246
10.006
38.442
1.00
44.83

1DLC
3221


ATOM
3098
N
SER
441
27.177
11.035
40.794
1.00
36.81

1DLC
3222


ATOM
3099
CA
SER
441
25.851
10.483
41.087
1.00
36.80

1DLC
3223


ATOM
3100
C
SER
441
25.825
8.972
40.882
1.00
39.60

1DLC
3224


ATOM
3101
O
SER
441
25.000
8.271
41.467
1.00
40.38

1DLC
3225


ATOM
3102
CB
SER
441
24.781
11.133
40.212
1.00
33.16

1DLC
3226


ATOM
3103
OG
SER
441
24.910
10.741
38.857
1.00
34.23

1DLC
3227


ATOM
3104
N
LYS
442
26.730
8.495
40.039
1.00
41.35

1DLC
3228


ATOM
3105
CA
LYS
442
26.901
7.078
39.701
1.00
45.48

1DLC
3229


ATOM
3106
C
LYS
442
25.977
6.509
38.618
1.00
46.07

1DLC
3230


ATOM
3107
O
LYS
442
26.260
5.446
38.055
1.00
49.36

1DLC
3231


ATOM
3108
CD
LYS
442
26.905
6.192
40.953
1.00
49.45

1DLC
3232


ATOM
3109
CG
LYS
442
28.279
5.606
41.309
1.00
56.04

1DLC
3233


ATOM
3110
CD
LYS
442
28.626
4.379
40.416
1.00
58.91

1DLC
3234


ATOM
3111
CE
LYS
442
29.111
4.762
39.050
1.00
60.19

1DLC
3235


ATOM
3112
NZ
LYS
442
28.866
3.683
38.044
1.00
60.75

1DLC
3236


ATOM
3113
N
ARG
443
24.885
7.201
38.310
1.00
43.51
1
1DLC
3237


ATOM
3114
CA
ARG
443
24.001
6.738
37.247
1.00
40.12
1
1DLC
3238


ATOM
3115
C
ARG
443
23.716
7.807
36.191
1.00
39.29
1
1DLC
3239


ATOM
3116
O
ARG
443
23.231
8.897
36.498
1.00
39.09
1
1DLC
3240


ATOM
3117
CB
AARG
443
22.686
6.168
37.792
0.50
39.58
1
1DLC
3241


ATOM
3118
CB
BARG
443
22.701
6.194
37.849
0.50
39.12
1
1DLC
3242


ATOM
3119
CG
AARG
443
21.828
5.580
36.678
0.50
38.20
1
1DLC
3243


ATOM
3120
CG
BARG
443
21.551
6.015
36.868
0.50
37.50
1
1DLC
3244


ATOM
3121
CD
AARG
443
20.703
4.678
37.156
0.50
38.35
1
1DLC
3245


ATOM
3122
CD
BARG
443
20.501
5.057
37.433
0.50
36.41
1
1DLC
3246


ATOM
3123
NE
AARG
443
20.266
3.824
36.050
0.50
38.24
1
1DLC
3247


ATOM
3124
NE
BARG
443
20.317
5.184
38.857
0.50
34.60
1
1DLC
3248


ATOM
3125
CZ
AARG
443
19.076
3.238
35.951
0.50
37.74
1
1DLC
3249


ATOM
3126
CZ 
BARG
443
19.823
4.226
39.636
0.50
34.26
1
1DLC
3250


ATOM
3127
NH1
AARG
443
18.160
3.392
36.895
0.50
38.52
1
1DLC
3251


ATOM
3128
NH1
BARG
443
19.452
3.064
39.110
0.50
31.83
1
1DLC
3252


ATOM
3129
NH2
AARG
443
18.798
2.508
34.882
0.50
37.87
1
1DLC
3253


ATOM
3130
NH2
BARG
443
19.727
4.418
40.948
0.50
31.14
1
1DLC
3254


ATOM
3131
N
ASN
444
24.070
7.481
34.950
1.00
40.97

1DLC
3255


ATOM
3132
CA
ASN
444
23.882
8.350
33.784
1.00
41.75

1DLC
3256


ATOM
3133
C
ASN
444
24.271
9.814
34.045
1.00
42.79

1DLC
3257


ATOM
3134
O
ASN
444
23.421
10.700
34.174
1.00
42.71

1DLC
3258


ATOM
3135
CB
ASN
444
22.446
8.230
33.271
1.00
43.21

1DLC
3259


ATOM
3136
CG
ASN
444
22.260
8.764
31.862
1.00
44.75

1DLC
3260


ATOM
3137
OD1
ASN
444
23.258
9.086
31.182
1.00
47.47

1DLC
3261


ATOM
3138
ND2
ASN
444
21.040
8.867
31.418
1.00
45.66

1DLC
3262


ATOM
3139
N
VAL
445
25.579
10.041
34.079
1.00
42.96

1DLC
3263


ATOM
3140
CA
VAL
445
26.195
11.345
34.342
1.00
41.13

1DLC
3264


ATOM
3141
C
VAL
445
26.035
12.460
33.282
1.00
39.24

1DLC
3265


ATOM
3142
O
VAL
445
26.037
13.641
33.602
1.00
41.51

1DLC
3266


ATOM
3143
CB
VAL
445
27.694
11.117
34.702
1.00
41.94

1DLC
3267


ATOM
3144
CG1
VAL
445
28.516
12.385
34.554
1.00
43.22

1DLC
3268


ATOM
3145
CG2
VAL
445
27.796
10.562
36.116
1.00
37.86

1DLC
3269


ATOM
3146
N
GLY
446
25.888
12.108
32.020
1.00
38.45

1DLC
3270


ATOM
3147
CA
GLY
446
25.737
13.157
31.032
1.00
37.87

1DLC
3271


ATOM
3148
C
GLY
446
27.023
13.933
30.806
1.00
38.06

1DLC
3272


ATOM
3149
O
GLY
446
28.108
13.458
31.137
1.00
39.17

1DLC
3273


ATOM
3150
N
ALA
447
26.899
15.146
30.276
1.00
38.09

1DLC
3274


ATOM
3151
CA
ALA
447
28.060
15.960
29.973
1.00
37.35

1DLC
3275


ATOM
3152
C
ALA
447
28.222
17.226
30.847
1.00
35.81

1DLC
3276


ATOM
3153
O
ALA
447
27.291
17.651
31.535
1.00
35.86

1DLC
3277


ATOM
3154
CB
ALA
447
29.043
16.373
28.490
1.00
38.30

1DLC
3278


ATOM
3155
N
VAL
448
29.426
17.794
30.818
1.00
33.69

1DLC
3279


ATOM
3156
CA
VAL
448
29.736
18.992
31.590
1.00
32.06

1DLC
3280


ATOM
3157
C
VAL 
448
29.041
20.194
30.976
1.00
30.84

1DLC
3281


ATOM
3158
O
VAL
448
29.117
20.413
29.771
1.00
30.03

1DLC
3282


ATOM
3159
CB
VAL 
448
31.275
19.263
31.695
1.00
30.42

1DLC
3281


ATOM
3160
CG1
VAL 
448
31.936
18.203
32.547
1.00
30.39

1DLC
3284


ATOM
3161
CG2
VAL
448
31.919
19.283
30.334
1.00
28.17

1DLC
3285


ATOM
3162
N
SER
449
28.324
20.942
31.805
1.00
29.95

1DLC
3286


ATOM
3163
CA
SER
449
27.609
22.116
31.326
1.00
10.08

1DLC
3287


ATOM
3164
C
SER
449
27.940
23.393
32.100
1.00
29.27

1DLC
3288


ATOM
3165
O
SER
449
27.571
24.486
31.675
1.00
29.45

1DLC
3289


ATOM
3166
CB
SER
449
26.093
21.875
31.386
1.00
31.17

1DLC
3290


ATOM
3167
OG 
SER
449
25.616
21.864
32.723
1.00
32.27

1DLC
3291


ATOM
3168
N
TRP
450
28.666
23.264
33.206
1.00
26.45

1DLC
3292


ATOM
3169
CA
TRP
450
28.993
24.427
34.023
1.00
24.97

1DLC
3293


ATOM
3170
C
TRP 
450
30.444
24.442
34.525
1.00
25.78

1DLC
3294


ATOM
3171
O
TRP 
450
30.903
23.514
35.193
1.00
26.98

1DLC
3295


ATOM
3172
CB
TRP 
450
28.003
24.475
35.198
1.00
22.55

1DLC
3296


ATOM
3173
CO 
TRP 
450
28.003
25.718
36.062
1.00
24.05

1DLC
3297


ATOM
3174
CD1
TRP 
450
27.071
26.723
36.046
1.00
24.31

1DLC
3298


ATOM
3175
CD2
TRP 
450
28.864
25.994
37.181
1.00
22.36

1DLC
3299


ATOM
3176
NE1
TRP 
450
27.282
27.585
37.101
1.00
24.38

1DLC
3300


ATOM
3177
CE2
TRP 
450
28.376
27.163
37.809
1.00
22.02

1DLC
3301


ATOM
3178
CE3
TRP 
450
29.989
25.361
37.719
1.00
23.01

1DLC
3302


ATOM
3179
CZ2
TRP 
450
28.970
27.705
38.946
1.00
23.92

1DLC
3303


ATOM
3180
CZ3
TRP 
450
30.579
25.902
38.852
1.00
23.85

1DLC
3304


ATOM
3181
CR2
TRP
450
30.068
27.062
39.451
1.00
24.68

1DLC
3305


ATOM
3182
N
ASP 
451
31.148
25.529
34.227
1.00
26.82

1DLC
3306


ATOM
3183
CA
ASP
451
32.541
25.703
34.640
1.00
23.64

1DLC
3307


ATOM
3184
C
ASP 
451
32.701
27.046
35.359
1.00
22.66

1DLC
3308


ATOM
3185
O
ASP
451
32.479
28.103
34.760
1.00
20.61

1DLC
3309


ATOM
3186
CB
ASP 
451
33.451
25.675
33.406
1.00
22.67

1DLC
3310


ATOM
3187
CG
ASP 
451
34.920
25.461
33.749
1.00
24.25

1DLC
3311


ATOM
3188
OD1
ASP 
451
35.325
25.616
34.919
1.00
24.75

1DLC
3112


ATOM
3189
OD2
ASP
451
35.674
25.116
32.824
1.00
24.52

1DLC
3313


ATOM
3190
N
SER
452
33.106
27.001
36.629
1.00
20.91

1DLC
3314


ATOM
3191
CA
SER
452
33.307
28.219
37.432
1.00
22.01

1DLC
3315


ATOM
3192
C
SER
452
34.262
29.231
36.786
1.00
23.43

1DLC
3316


ATOM
3193
O
SER
452
34.036
30.443
36.833
1.00
23.61

1DLC
3317


ATOM
3194
CB
SER 
452
33.799
27.868
38.840
1.00
20.07

1DLC
3318


ATOM
3195
OG 
SER
452
34.950
27.049
38.793
1.00
22.47

1DLC
3319


ATOM
3196
N
ILE
453
35.291
28.724
36.122
1.00
25.73

1DLC
3320


ATOM
3197
CA
ILE
453
36.272
29.571
35.454
1.00
27.62

1DLC
3321


ATOM
3198
C
ILE
453
35.641
30.563
34.469
1.00
25.55

1DLC
3322


ATOM
3199
O
ILE
453
36.181
31.645
34.255
1.00
28.13

1DLC
3323


ATOM
3200
CB
ILE
453
37.383
28.691
34.786
1.00
29.82

1DLC
3324


ATOM
3201
CGI
ILE 
453
38.345
28.183
35.866
1.00
35.65

1DLC
3325


ATOM
3202
CO2
ILE 
453
38.154
29.446
33.730
1.00
32.32

1DLC
3326


ATOM
3203
CD1
ILE 
453
38.910
29.287
36.786
1.00
36.52

1DLC
3327


ATOM
3204
N
ASP
454
34.474
30.225
33.926
1.00
22.83

1DLC
3328


ATOM
3205
CA
ASP
454
33.786
31.107
32.982
1.00
22.88

1DLC
3329


ATOM
3206
C
ASP
454
33.256
32.362
33.663
1.00
23.05

1DLC
3330


ATOM
3207
O
ASP
454
33.097
33.412
33.034
1.00
22.70

1DLC
3131


ATOM
3208
CB
ASP
454
32.598
30.397
32.337
1.00
29.00

1DLC
3332


ATOM
3209
CG
ASP 
454
33.000
29.187
31.533
1.00
36.53

1DLC
3333


ATOM
3210
OD1
ASP
454
33.975
29.279
30.749
1.00
38.64

1DLC
3334


ATOM
3211
OD2
ASP 
454
32.322
28.144
31.679
1.00
42.72

1DLC
3335


ATOM
3212
N
GLN 
455
32.929
32.226
34.943
1.00
21.53

1DLC
3336


ATOM
3213
CA
GLN
455
32.388
33.330
35.711
1.00
19.71

1DLC
3337


ATOM
3214
C
GLN 
455
33.440
33.991
36.574
1.00
21.92

1DLC
3313


ATOM
3215
O
GLN
455
33.399
35.198
36.801
1.00
26.53

1DLC
3339


ATOM
3216
CB
GLN
455
31.223
32.834
36.555
1.00
16.77

1DLC
3340


ATOM
3217
CG
GLN
455
30.108
32.308
35.690
1.00
22.31

1DLC
3341


ATOM
3218
CD
GLN
455
29.012
31.629
36.475
1.00
23.60

1DLC
3342


ATOM
3219
OE1
GLN
455
28.575
32.150
37.468
1.00
24.05

1DLC
3343


ATOM
3220
NE2
GLN
455
28.628
30.449
36.042
1.00
27.92

1DLC
3344


ATOM
3221
N
LEU
456
14.388
33.197
37.054
1.00
23.05

1DLC
3345


ATOM
3222
CA
LEU
456
35.469
33.709
37.894
1.00
22.56

1DLC
3346


ATOM
3223
C
LEU
456
36.813
33.349
37.274
1.00
20.68

1DLC
3347


ATOM
3224
O
LEU
456
37.508
32.440
37.730
1.00
19.98

1DLC
3348


ATOM
3225
CB
LEU
456
35.357
33.149
39.316
1.00
20.94

1DLC
3349


ATOM
3226
CG
LEU
456
34.034
33.435
40.044
1.00
22.46

1DLC
3350


ATOM
3227
CD1
LEU
456
34.021
32.668
41.344
1.00
21.63

1DLC
3351


ATOM
3228
CD2
LEU
456
33.850
34.935
40.297
1.00
17.51

1DLC
3352


ATOM
3229
N
PRO
457
37.193
34.071
36.211
1.00
21.65

1DLC
3353


ATOM
3230
CA
PRO
457
38.453
33.850
35.500
1.00
22.86

1DLC
3354


ATOM
3231
C
PRO
457
39.648
33.998
36.454
1.00
25.36

1DLC
3355


ATOM
3232
O
PRO
457
39.500
34.486
37.585
1.00
23.67

1DLC
3356


ATOM
3233
CB
PRO
457
38.450
34.975
34.458
1.00
21.76

1DLC
3357


ATOM
3234
CG
PRO
457
37.016
35.300
34.277
1.00
20.92

1DLC
3358


ATOM
3235
CD
PRO
457
36.495
35.251
35.673
1.00
19.85

1DLC
3359


ATOM
3236
N
PRO
458
40.843
33.557
36.022
1.00
25.47

1DLC
3360


ATOM
3237
CA
PRO
458
42.028
33.671
36.878
1.00
24.94

1DLC
3381


ATOM
3238
C
PRO
458
42.597
35.093
36.789
1.00
25.68

1DLC
3362


ATOM
3239
O
PRO
458
42.340
35.818
35.819
1.00
22.11

1DLC
3363


ATOM
3240
CB
PRO
458
43.008
32.672
36.251
1.00
24.27

1DLC
3364


ATOM
3241
CG
PHO
458
42.197
31.916
35.224
1.00
26.36

1DLC
3365


ATOM
3242
CD
PRO
458
41.187
32.894
34.759
1.00
23.11

1DLC
3366


ATOM
3243
N
GLU
459
43.343
35.504
37.809
1.00
26.71

1DLC
3367


ATOM
3244
CA
GLU
459
43.950
36.827
37.788
1.00
33.63

1DLC
3368


ATOM
3245
C
GLU
459
44.956
36.884
36.646
1.00
37.69

1DLC
3369


ATOM
3246
O
GLU
459
45.090
37.907
35.971
1.00
37.94

1DLC
3370


ATOM
3247
CB
GLU
459
44.654
37.129
39.106
1.00
34.45

1DLC
3371


ATOM
3248
CG
GLU
459
43.711
37.364
40.269
1.00
38.75

1DLC
3372


ATOM
3249
CD
GLU
459
44.438
37.530
41.590
1.00
40.23

1DLC
3373


ATOM
3250
OE1
GLU
459
45.678
37.372
41.614
1.00
44.97

1DLC
3374


ATOM
3251
OE2
GLU
459
43.772
37.811
42.610
1.00
41.43

1DLC
3375


ATOM
3252
N
THR
460
45.640
35.765
36.419
1.00
42.42

1DLC
3376


ATOM
3253
CA
THR
460
46.634
35.668
35.352
1.00
46.99

1DLC
3377


ATOM
3254
C
THR
460
46.516
34.423
34.495
1.00
48.85

1DLC
3378


ATOM
3255
O
THR
460
46.385
33.310
35.006
1.00
49.59

1DLC
3379


ATOM
3256
CB
THR
460
48.091
35.669
35.892
1.00
47.16

1DLC
3180


ATOM
3257
CG1
TER
460
48.212
34.744
36.980
1.00
48.60

1DLC
3381


ATOM
3258
CG2
THR
460
48.502
37.051
36.348
1.00
52.25

1DLC
3382


ATOM
3259
N
THR
461
46.583
34.625
33.185
1.00
52.04

1DLC
3383


ATOM
3260
CA
THR
461
46.555
33.524
32.231
1.00
55.43

1DLC
3384


ATOM
3261
C
THR
461
48.009
33.128
31.950
1.00
59.08

1DLC
3385


ATOM
3262
O
THR
461
48.290
32.305
31.077
1.00
62.04

1DLC
3386


ATOM
3263
CB
THR
461
45.898
33.942
30.914
1.00
55.22

1DLC
3387


ATOM
3264
OG1
THR
461
46.513
35.143
30.440
1.00
57.54

1DLC
3188


ATOM
3265
CG2
THR
461
44.419
34.183
31.113
1.00
54.73

1DLC
3389


ATOM
3266
N
ASP
462
48.929
33.768
32.668
1.00
61.13

1DLC
3390


ATOM
3267
CA
ASP
462
50.355
33.499
32.542
1.00
63.77

1DLC
3391


ATOM
3268
C
ASP
462
50.749
32.240
33.319
1.00
62.37

1DLC
3392


ATOM
3269
O
ASP
462
51.321
31.308
32.757
1.00
63.78

1DLC
3393


ATOM
3270
CB
ASP
462
51.162
34.700
33.054
1.00
70.21

1DLC
3394


ATOM
3271
CG
ASP
462
51.831
35.485
31.930
1.00
76.55

1DLC
3395


ATOM
3272
OD1
ASP
462
51.191
35.686
30.871
1.00
79.02

1DLC
3396


ATOM
3273
OD2
ASP
462
53.004
35.901
32.110
1.00
79.69

1DLC
3397


ATOM
3274
N
GLU
463
50.437
32.224
34.612
1.00
60.14

1DLC
3398


ATOM
3275
CA
GLU
463
50.752
31.090
35.483
1.00
58.33

1DLC
3399


ATOM
3276
C
GLU
463
49.703
29.968
35.441
1.00
55.57

1DLC
3400


ATOM
3277
O
GLU
463
48.610
30.140
34.890
1.00
57.13

1DLC
3401


ATOM
3278
CB
GLU
463
50.886
31.575
36.922
1.00
60.04

1DLC
3402


ATOM
1279
CG
GLU
463
51.932
32.639
37.123
1.00
69.89

1DLC
3403


ATOM
3280
CD
GLU
463
52.244
32.859
38.594
1.00
77.10

1DLC
3404


ATOM
3281
OE1
GLU
463
51.402
33.458
39.308
1.00
79.81

1DLC
3405


ATOM
3282
OE2
GLU
463
53.331
32.418
39.041
1.00
81.43

1DLC
3406


ATOM
3283
N
PRO
464
50.034
28.785
35.996
1.00
51.32

1DLC
3407


ATOM
3284
CA
PRO
464
49.045
27.702
35.982
1.00
47.85

1DLC
3408


ATOM
3285
C
PRO
464
47.898
28.044
36.955
1.00
44.75

1DLC
3409


ATOM
3286
O
PRO
464
48.124
28.725
37.963
1.00
41.10

1DLC
3410


ATOM
3287
CB
PRO
464
49.867
26.486
36.435
1.00
47.06

1DLC
3411


ATOM
3288
CG
PRO
464
50.929
27.067
37.300
1.00
46.21

1DLC
3412


ATOM
3289
CD
PRO
454
51.328
28.309
36.521
1.00
48.64

1DLC
3413


ATOM
3290
N
LEU
465
46.686
27.570
36.657
1.00
41.80

1DLC
3414


ATOM
3291
CA
LEU
465
45.497
27.853
37.475
1.00
37.33

1DLC
3415


ATOM
3292
C
LEU
465
45.658
27.777
38.992
1.00
35.76

1DLC
3416


ATOM
3293
O
LEU
465
45.174
28.655
39.707
1.00
34.89

1DLC
3417


ATOM
3294
CB
LEU
465
44.311
26.981
37.047
1.00
38.95

1DLC
3418


ATOM
3295
CG
LEU
465
43.043
27.695
36.542
1.00
40.98

1DLC
3419


ATOM
3296
CD1
LEU
465
41.879
26.706
36.476
1.00
41.37

1DLC
3420


ATOM
3297
CD2
LEU
465
42.673
28.853
37.448
1.00
38.54

1DLC
3421


ATOM
3298
N
GLU
466
46.341
26.749
39.489
1.00
31.43

1DLC
3422


ATOM
3299
CA
GLU
466
46.534
26.620
40.930
1.00
32.27

1DLC
3423


ATOM
3300
C
GLU
466
47.368
27.763
41.518
1.00
31.84

1DLC
3424


ATOM
3301
O
GLU
466
47.493
27.895
42.737
1.00
33.28

1DLC
3425


ATOM
3302
CR 
0131
466
47.144
25.263
41.300
1.00
35.86

1DLC
3426


ATOM
3303
CG
GLU
466
48.603
25.078
40.917
1.00
41.48

1DLC
3427


ATOM
3304
CD
GLU
466
48.789
24.358
39.595
1.00
43.01

1DLC
3428


ATOM
3305
OE1
GLU
466
48.001
24.585
38.650
1.00
43.46

1DLC
3429


ATOM
3306
OE2
GLU
466
49.737
23.552
39.506
1.00
49.70

1DLC
3430


ATOM
3307
N
LYS
467
47.959
28.568
40.643
1.00
30.87

1DLC
3431


ATOM
3308
CA
LYS
467
48.753
29.716
41.071
1.00
34.88

1DLC
3432


ATOM
3309
C
LYS
467
48.053
31.033
40.739
1.00
30.95

1DLC
3433


ATOM
3310
O
LYS
467
48.050
31.955
41.537
1.00
34.01

1DLC
3414


ATOM
3311
CB
LYS
467
50.126
29.727
40.395
1.00
41.82

1DLC
3435


ATOM
3312
CG
LYS
467
51.091
26.619
40.704
1.00
48.67

1DLC
3436


ATOM
3313
CD
LYS
467
52.383
28.821
39.991
1.00
59.85

1DLC
3437


ATOM
3314
CE
LYS
467
53.387
27.682
40.140
1.00
63.85

1DLC
3438


ATOM
3315
NZ
LYS
467
54.585
27.912
39.262
1.00
63.42

1DLC
3439


ATOM
3316
N
GLY
468
47.462
31.113
39.553
1.00
29.04

1DLC
3440


ATOM
3317
CA
GLY
468
46.806
32.342
39.136
1.00
28.69

1DLC
3441


ATOM
3318
C
GLY
468
45.319
32.552
39.384
1.00
27.26

1DLC
3442


ATOM
3319
O
GLY
468
44.794
33.614
39.036
1.00
26.73

1DLC
3443


ATOM
3320
N
TYR
469
44.640
31.570
39.977
1.00
23.94

1DLC
3444


ATOM
3321
CA
TYR
469
43.207
31.689
40.243
1.00
23.65

1DLC
3445


ATOM
3322
C
TYR
469
42.874
32.954
41.064
1.00
26.78

1DLC
3446


ATOM
3323
O
TYR
469
43.728
33.498
41.762
1.00
29.85

1DLC
3447


ATOM
3324
CB
TYR
469
42.687
30.427
40.931
1.00
18.50

1DLC
3448


ATOM
3325
CG
TYR
469
43.069
30.300
42.384
1.00
18.68

1DLC
3449


ATOM
3326
CD1
TYR
459
44.253
29.668
42.771
1.00
18.59

1DLC
3450


ATOM
3327
CD2
TYR
469
42.228
30.789
43.381
1.00
17.48

1DLC
3451


ATOM
3328
CE1
TYR
469
44.581
29.526
44.119
1.00
18.20

1DLC
3452


ATOM
3329
CE2
TYR
469
42.543
30.655
44.722
1.00
17.54

1DLC
3453


ATOM
3330
CZ 
TYR
469
43.715
30.025
45.088
1.00
19.23

1DLC
3454


ATOM
3331
OH
TYR
469
43.999
29.900
46.427
1.00
24.58

1DLC
3455


ATOM
3332
N
SER
470
41.637
33.430
40.970
1.00
26.56

1DLC
3456


ATOM
3333
CA
SER
470
41.235
34.646
41.684
1.00
26.36

1DLC
3457


ATOM
3334
C
SER
470
40.278
34.460
42.861
1.00
25.81

1DLC
3450


ATOM
3335
O
SEE
470
40.118
35.364
43.689
1.00
27.24

1DLC
3459


ATOM
3336
CD
SER 
470
40.604
35.631
40.701
1.00
26.16

1DLC
3460


ATOM
3337
OG 
SER 
470
39.445
35.070
40.106
1.00
24.14

1DLC
3461


ATOM
3338
N
HIS 
471
39.623
33.305
42.926
1.00
24.96

1DLC
3462


ATOM
3339
CA
HIS 
471
38.656
33.025
43.986
1.00
22.21

1DLC
3463


ATOM
3340
C
HIS 
471
38.652
31.573
44.426
1.00
20.34

1DLC
3464


ATOM
3341
O
HIS 
471
39.004
30.685
43.666
1.00
20.23

1DLC
3465


ATOM
3342
CB
HIS 
471
37.234
33.342
43.501
1.00
24.72

1DLC
3466


ATOM
3343
CG
HIS 
471
36.951
34.800
43.306
1.00
24.47

1DLC
3467


ATOM
3344
ND1
HIS 
471
37.260
35.474
42.142
1.00
22.67

1DLC
3468


ATOM
3345
CD2
HIS 
471
36.328
35.699
44.106
1.00
22.96

1DLC
3469


ATOM
3346
CE1
HIS 
471
36.835
36.720
42.232
1.00
22.12

1DLC
3470


ATOM
3347
NE2
HIS 
471
36.265
36.881
43.415
1.00
21.11

1DLC
3471


ATOM
3348
N
GLN 
472
38.180
31.334
45.638
1.00
19.76

1DLC
3472


ATOM
3349
CA
GLN
472
38.079
29.979
46.155
1.00
20.82

1DLC
3473


ATOM
3350
C
GLN 
472
36.680
29.724
46.709
1.00
22.36

1DLC
3474


ATOM
3351
O
GLN
472
35.976
30.664
47.097
1.00
22.13

1DLC
3475


ATOM
3352
CD
GLN
472
39.120
29.740
47.230
1.00
22.23

1DLC
3476


ATOM
3353
CG
GLN 
472
39.115
30.769
48.313
1.00
29.71

1DLC
3477


ATOM
3354
CD
GLN 
472
40.248
30.552
49.280
1.00
40.11

1DLC
3478


ATOM
3355
OE1
GLN 
472
40.174
29.680
50.151
1.00
41.87

1DLC
3479


ATOM
3356
NE2
GLN
472
41.326
31.317
49.116
1.00
44.52

1DLC
3480


ATOM
3357
N
LEU 
473
36.277
28.455
46.731
1.00
23.05

1DLC
3481


ATOM
3358
CA
LEU
473
34.959
28.054
47.221
1.00
20.06

1DLC
3482


ATOM
3359
C
LEU 
473
34.794
28.248
48.725
1.00
20.03

1DLC
3483


ATOM
3360
O
LEU 
473
35.637
27.833
49.517
1.00
19.02

1DLC
3484


ATOM
3361
CB
LEU 
473
34.678
26.587
46.876
1.00
21.51

1DLC
3485


ATOM
3362
CG
LEU 
473
33.401
26.198
46.118
1.00
22.58

1DLC
3486


ATOM
3363
CD1
LEU
473
33.188
24.714
46.270
1.00
20.29

1DLC
3487


ATOM
3364
CD2
LEU 
473
32.181
26.940
46.633
1.00
20.63

1DLC
3488


ATOM
3365
N
ASN 
474
33.685
28.862
49.108
1.00
20.98

1DLC
3489


ATOM
3366
CA
ASN
474
33.394
29.103
50.508
1.00
22.93

1DLC
3490


ATOM
3367
C
ASN 
474
32.087
28.434
50.936
1.00
22.97

1DLC
3491


ATOM
3368
O
ASN 
474
31.975
27.922
52.056
1.00
23.74

1DLC
3492


ATOM
3369
CB
ASN 
474
33.327
30.612
50.777
1.00
24.38

1DLC
3493


ATOM
3370
CG
ASN 
474
33.068
30.941
52.247
1.00
29.78

1DLC
3494


ATOM
3371
OD1
ASN 
474
32.237
31.760
52.563
1.00
38.30

1DLC
3495


ATOM
3372
ND2
ASN
474
33.789
30.298
53.140
1.00
29.37

1DLC
3496


ATOM
3373
N
TYR
475
31.119
28.383
50.028
1.00
21.61

1DLC
3497


ATOM
3374
CA
TYR
475
29.824
27.812
50.376
1.00
21.74

1DLC
3498


ATOM
3375
C
TYR
475
29.081
27.125
49.244
1.00
20.48

1DLC
3499


ATOM
3376
O
TYR
475
29.219
27.472
48.069
1.00
18.90

1DLC
3500


ATOM
3377
CH
TYR
475
28.922
28.910
50.958
1.00
22.80

1DLC
3501


ATOM
3378
CG
TYR 
475
28.050
28.481
52.117
1.00
23.56

1DLC
3502


ATOM
3379
CD1
TYR
475
20.601
28.258
53.379
1.00
27.52

1DLC
3503


ATOM
3380
CD2
TYR 
475
26.672
28.324
51.963
1.00
23.00

1DLC
3504


ATOM
3381
CE1
TYR 
475
27.802
27.895
54.464
1.00
26.40

1DLC
3505


ATOM
3382
CE2
TYR 
475
25.859
27.958
53.043
1.00
24.16

1DLC
3506


ATOM
3383
CZ 
TYR 
475
26.430
27.746
54.291
1.00
25.06

1DLC
3507


ATOM
3384
OH
TYR
475
25.643
27.405
55.375
1.00
26.34

1DLC
3508


ATOM
3385
N
VAL 
476
28.273
26.150
49.638
1.00
21.63

1DLC
3509


ATOM
3386
CA
VAL
476
27.444
25.379
48.724
1.00
22.28

1DLC
3510


ATOM
3387
C
VAL 
476
26.046
25.309
49.355
1.00
23.25

1DLC
3511


ATOM
3388
O
VAL 
476
25.905
25.032
50.546
1.00
22.42

1DLC
3512


ATOM
3389
CB
VAL 
476
28.026
23.958
48.499
1.00
19.04

1DLC
3513


ATOM
3390
CG1
VAL
476
27.025
23.077
47.813
1.00
20.37

1DLC
3514


ATOM
3391
CG2
VAL 
476
29.269
24.040
47.640
1.00
20.33

1DLC
3515


ATOM
3392
N
MET
477
25.026
25.652
48.575
1.00
22.47

1DLC
3516


ATOM
3393
CA
MET
477
23.655
25.627
49.069
1.00
22.92

1DLC
3517


ATOM
3394
C
MET
477
22.722
25.110
47.973
1.00
23.63

1DLC
3518


ATOM
3395
O
MET
477
22.819
25.531
46.825
1.00
24.06

1DLC
3519


ATOM
3396
CB
MET
477
23.246
27.030
49.517
1.00
24.95

1DLC
3520


ATOM
3397
CG
MET
477
22.027
27.076
50.406
1.00
34.31

1DLC
3521


ATOM
3398
SD
MET
477
21.578
26.761
50.913
1.00
36.69

1DLC
3522


ATOM
3399
CE
MET
477
22.689
29.015
52.281
1.00
38.04

1DLC
3523


ATOM
3400
N
CYS
478
21.870
24.150
48.327
1.00
25.18

1DLC
3524


ATOM
3401
CA
CYS
478
20.912
23.551
47.390
1.00
23.36

1DLC
3525


ATOM
3402
C
CYS
478
19.507
24.106
47.568
1.00
23.41

1DLC
3526


ATOM
3403
O
CYS
478
18.970
24.102
48.673
1.00
23.01

1DLC
3527


ATOM
3404
CB
CYS
478
20.843
22.029
47.564
1.00
21.73

1DLC
3528


ATOM
3405
SG
CYS
478
22.219
21.086
46.881
1.00
24.07

1DLC
3529


ATOM
3406
N
PHE
479
18.918
24.585
46.481
1.00
21.93

1DLC
3530


ATOM
3407
CA
PHE
479
17.563
25.118
46.513
1.00
19.16

1DLC
3531


ATOM
3408
C
PHE
479
16.629
24.149
45.814
1.00
20.36

1DLC
3532


ATOM
3409
O
PHE
479
17.032
23.431
44.897
1.00
13.20

1DLC
3533


ATOM
3410
CB
PHE
479
17.496
26.483
45.831
1.00
16.90

1DLC
3534


ATOM
3411
CG
PHE
479
18.194
27.563
46.592
1.00
19.07

1DLC
3535


ATOM
3412
CD1
PHE
479
17.550
28.229
47.625
1.00
20.04

1DLC
3536


ATOM
3413
CD2
PHE
479
19.509
27.891
46.308
1.00
17.03

1DLC
3537


ATOM
3414
CE1
PHE
479
18.210
29.207
48.368
1.00
22.59

1DLC
3538


ATOM
3415
CE2
PHE
479
20.173
28.866
47.044
1.00
23.10

1DLC
3539


ATOM
3416
CZ
PHE
479
19.525
29.524
48.075
1.00
18.71

1DLC
3540


ATOM
3417
N
LEU
480
15.384
24.102
46.269
1.00
21.81

1DLC
3541


ATOM
3418
CA
LEU
480
14.402
23.219
45.661
1.00
19.96

1DLC
3542


ATOM
3419
C
LEU
480
13.581
23.952
44.611
1.00
20.47

1DLC
3543


ATOM
3420
O
LEU
480
13.229
25.117
44.798
1.00
22.01

1DLC
3544


ATOM
3421
CB
LEU
480
13.474
22.629
46.719
1.00
16.36

1DLC
3545


ATOM
3422
CG
LEU
480
11.071
21.574
47.653
1.01
18.70

1DLC
3546


ATOM
3423
CD1
LEU
480
13.045
21.170
48.675
1.00
16.09

1DLC
3547


ATOM
3424
CD2
LEU
480
14.535
20.367
46.863
1.00
17.11

1DLC
3548


ATOM
3425
N
MET
481
13.375
23.300
43.473
1.00
19.08

1DLC
3549


ATOM
3426
CA
MET
481
12.557
23.875
42.411
1.00
21.22

1DLC
3550


ATOM
3427
C
MET
481
11.091
23.844
42.867
1.00
24.48

1DLC
3551


ATOM
3428
O
MET
481
10.729
23.084
43.772
1.00
25.50

1DLC
3552


ATOM
3429
CB
MET
481
12.674
23.055
41.133
1.00
18.69

1DLC
3553


ATOM
3430
CG
MET
481
14.002
23.129
40.458
1.00
20.79

1DLC
3554


ATOM
3431
SD
MET
481
13.988
22.032
39.060
1.00
25.38

1DLC
3555


ATOM
3432
CE
MET
481
15.738
21.837
38.753
1.00
21.04

1DLC
3556


ATOM
3413
N
GLN
482
10.251
24.662
42.241
1.00
25.74

1DLC
3557


ATOM
3434
CA
GLN
482
8.836
24.705
42.579
1.00
24.89

1DLC
3558


ATOM
3435
C
GLN
482
8.143
23.390
42.282
1.00
26.77

1DLC
3559


ATOM
3436
O
GLN
482
8.469
22.713
41.311
1.00
26.04

1DLC
3560


ATOM
3437
CB
GLN
482
8.153
25.834
41.840
1.00
22.45

1DLC
3561


ATOM
3438
CG
GLN
482
8.516
27.182
42.390
1.00
24.04

1DLC
3562


ATOM
3439
CD
GLN
482
7.592
28.241
41.888
1.00
25.93

1DLC
3563


ATOM
3440
OE1
GLN
482
6.758
28.740
42.630
1.00
33.56

1DLC
3564


ATOM
3441
NE2
GLN
482
7.697
28.565
40.617
1.00
24.90

1DLC
3565


ATOM
3442
N
GLY
483
7.200
23.017
43.141
1.00
31.29

1DLC
3566


ATOM
3443
CA
GLY
483
6.502
21.756
42.960
1.00
34.89

1DLC
3567


ATOM
3444
C
GLY
483
7.529
20.643
42.974
1.00
38.13

1DLC
3568


ATOM
3445
O
GLY
483
7.338
19.585
42.382
1.00
41.30

1DLC
3569


ATOM
3446
N
SER
484
8.644
20.928
43.539
1.00
40.46

1DLC
3570


ATOM
3447
CA
SER
484
9.781
20.027
43.760
1.00
39.19

1DLC
3571


ATOM
3448
C
SER
484
10.047
19.110
42.574
1.00
35.89

1DLC
3572


ATOM
3449
O
SER
484
9.982
17.891
42.582
1.00
34.78

1DLC
3573


ATOM
3450
CB
SER
484
9.716
19.258
45.070
1.00
44.00

1DLC
3574


ATOM
3451
OG
SER
484
9.864
20.160
46.158
1.00
49.80

1DLC
3575


ATOM
3452
N
ARG
485
10.322
19.728
41.430
1.00
34.10

1DLC
3576


ATOM
3453
CA
ARG
485
10.639
18.998
40.212
1.00
33.89

1DLC
3577


ATOM
3454
C
ARG
485
12.155
18.734
40.152
1.00
34.69

1DLC
3578


ATOM
3455
O
ARG
485
12.630
17.971
39.305
1.00
36.50

1DLC
3579


ATOM
3456
CR
ARG 
485
10.197
19.800
38.983
1.00
33.16

1DLC
3580


ATOM
3457
CG
ARG 
485
10.266
19.019
37.669
1.00
36.98

1DLC
3581


ATOM
3458
CD
ARG
485
9.882
19.889
36.485
1.00
41.59

1DLC
3582


ATOM
3459
NE
ARG
485
8.680
19.445
35.770
1.00
42.72

1DLC
3583


ATOM
3460
CZ
ARG
485
7.505
19.169
36.335
1.00
44.05

1DLC
3584


ATOM
3461
NH1
ARO 
485
7.332
19.265
37.647
1.00
44.99

1DLC
3585


ATOM
3462
NH2
ARG
485
6.470
18.863
35.569
1.00
47.30

1DLC
3S86


ATOM
3463
N
GLY
486
12.910
19.365
41.052
1.00
32.23

1DLC
3587


ATOM
3464
CA
GLY
486
14.352
19.174
41.068
1.00
29.57

1DLC
3588


ATOM
3465
C
GLY 
486
15.115
20.016
42.078
1.00
28.60

1DLC
3589


ATOM
3466
O
GLY 
486
14.511
20.692
42.919
1.00
25.84

1DLC
3590


ATOM
3467
N
THR 
487
16.443
19.992
41.966
1.00
25.86

1DLC
3591


ATOM
3468
CA
THR
487
17.337
20.732
42.862
1.00
24.67

1DLC
3592


ATOM
3469
C
THR 
487
18.295
21.665
42.121
1.00
25.25

1DLC
3593


ATOM
3470
O
THR 
487
18.962
21.260
41.164
1.00
25.06

1DLC
3594


ATOM
3471
CR
THR 
487
18.183
19.760
43.728
1.00
25.40

1DLC
3595


ATOM
3472
CG1
THR
487
17.344
19.141
44.707
1.00
26.03

1DLC
3596


ATOM
3473
CG2
THR
487
19.320
20.487
44.438
1.00
26.87

1DLC
3597


ATOM
3474
N
ILE
488
18.370
22.909
42.584
1.00
22.95

1DLC
3598


ATOM
3475
CA
ILE
488
19.257
23.915
41.993
1.00
24.06

1DLC
3599


ATOM
3476
C
ILE 
488
20.378
24.293
42.966
1.00
24.12

1DLC
3600


ATOM
3477
O
ILE
488
20.120
24.890
44.017
1.00
26.94

1DLC
3601


ATOM
3478
CB
ILE 
488
18.496
25.214
41.633
1.00
22.37

1DLC
3602


ATOM
3479
CG1
ILE 
488
17.343
24.915
40.668
1.00
21.27

1DLC
3603


ATOM
3480
CG2
ILE
488
19.456
26.225
41.020
1.00
16.51

1DLC
3604


ATOM
3481
CD1
ILE
488
16.468
26.115
40.375
1.00
20.81

1DLC
3605


ATOM
3482
N
PRO 
489
21.626
23.895
42.667
1.00
24.55

1DLC
3606


ATOM
3483
CA
PRO
489
22.741
24.239
43.567
1.00
22.62

1DLC
3607


ATOM
3484
C
PRO
489
23.285
25.646
43.290
1.00
20.82

1DLC
3608


ATOM
3485
O
PRO
489
23.321
26.094
42.137
1.00
22.41

1DLC
3609


ATOM
3486
CB
PRO
489
23.797
23.175
43.240
1.00
20.03

1DLC
3610


ATOM
3487
CG
PRO
489
23.028
22.083
42.522
1.00
22.59

1DLC
3611


ATOM
3488
CD
PRO 
489
22.052
22.876
41.695
1.00
20.82

1DLC
3612


ATOM
3489
N
VAL
490
23.663
26.340
44.353
1.00
10.80

1DLC
3613


ATOM
3490
CA
VAL
490
24.234
27.686
44.241
1.00
20.56

1DLC
3614


ATOM
3491
C
VAL
490
25.539
27.745
45.045
1.00
22.82

1DLC
3615


ATOM
3492
O
VAL
490
25.576
27.364
46.225
1.00
20.83

1DLC
3616


ATOM
3493
CB
VAL
490
23.257
28.772
44.732
1.00
22.17

1DLC
3617


ATOM
3494
CG1
VAL 
490
23.899
30.147
44.621
1.00
20.36

1DLC
3618


ATOM
3495
CG2
VAL 
490
21.989
28.740
43.895
1.00
24.80

1DLC
3619


ATOM
3496
N
LEU
491
26.610
28.206
44.397
1.00
22.64

1DLC
3620


ATOM
3497
CA
LEU
491
27.931
28.285
45.034
1.00
21.56

1DLC
3621


ATOM
3498
C
LEU 
491
28.397
29.704
45.377
1.00
19.56

1DLC
3622


ATOM
3499
O
LEU
491
28.279
30.622
44.566
1.00
21.15

1DLC
3623


ATOM
3500
CR
LEU
491
28.993
27.610
44.143
1.00
22.96

1DLC
3624


ATOM
3501
CG
LEU
491
28.739
26.213
43.549
1.00
22.44

1DLC
3625


ATOM
3502
CD1
LEU
491
29.970
25.728
42.817
1.00
19.64

1DLC
3626


ATOM
3503
CD2
LEU 
491
28.359
25.222
44.617
1.00
23.77

1DLC
3627


ATOM
3504
N
THR
492
28.926
29.867
46.584
1.00
17.65

1DLC
3628


ATOM
3505
CA
THR
492
29.451
31.153
47.050
1.00
21.18

1DLC
3629


ATOM
3506
C
THR 
492
30.987
31.103
47.093
1.00
24.42

1DLC
3630


ATOM
3507
O
THR 
492
31.580
30.111
47.545
1.00
25.76

1DLC
3631


ATOM
3508
CB
THR
492
28.927
31.503
48.451
1.00
20.37

1DLC
3632


ATOM
3509
CG1
THR
492
27.498
31.509
48.419
1.00
25.73

1DLC
3633


ATOM
3510
CG2
THR 
492
29.421
32.881
48.898
1.00
16.18

1DLC
3634


ATOM
3511
N
TRP 
493
31.622
32.184
46.638
1.00
23.37

1DLC
3635


ATOM
3512
CA
TRP
493
33.081
32.278
46.582
1.00
20.05

1DLC
3636


ATOM
3513
C
TRP 
493
33.650
33.491
47.311
1.00
19.63

1DLC
3637


ATOM
3514
O
TRP 
493
32.953
34.468
47.561
1.00
20.47

1DLC
3638


ATOM
3515
CB
TRP
493
33.546
32.333
45.123
1.00
16.78

1DLC
3639


ATOM
3516
CG
TRP
493
32.986
31.242
14.273
1.00
20.23

1DLC
3640


ATOM
3517
CD1
TRP
493
31.692
31.113
43.852
1.00
19.07

1DLC
3641


ATOM
3518
CD2
TRP
493
33.699
30.128
43.723
1.00
27.53

1DLC
3642


ATOM
3519
NE1
TRP
493
31.555
29.991
13.075
1.00
19.83

1DLC
3643


ATOM
3520
CE2
TRP
493
32.770
29.367
42.975
1.00
22.55

1DLC
3644


ATOM
3521
CE3
TRP
493
35.033
29.699
43.785
1.00
24.17

1DLC
3645


ATOM
3522
CZ2
TRP
493
33.132
28.198
42.294
1.00
22.22

1DLC
3646


ATOM
3523
CZ3
TRP
493
35.394
28.536
43.107
1.00
21.82

1DLC
3647


ATOM
3524
CH2
TRP
493
34.443
27.800
42.372
1.00
23.98

1DLC
3648


ATOM
3525
N
THR
494
34.930
33.402
47.661
1.00
19.10

1DLC
3649


ATOM
3526
CA
THR
494
35.643
34.488
48.323
1.00
15.75

1DLC
3650


ATOM
3527
C
THR
494
36.962
34.781
47.583
1.00
15.71

1DLC
3651


ATOM
3528
O
THR
494
37.497
33.923
46.885
1.00
15.53

1DLC
3652


ATOM
3529
CB
THR
494
35.867
34.299
49.832
1.00
17.76

1DLC
3653


ATOM
3530
CG1
THR
494
35.483
32.913
50.007
1.00
18.92

1DLC
3654


ATOM
3531
CG2
THR
494
34.530
34.232
50.580
1.00
13.45

1DLC
3655


ATOM
3532
N
HIS
495
37.448
36.011
47.679
1.00
17.73

1DLC
3656


ATOM
3533
CA
HIS
495
38.670
36.416
46.992
1.00
18.64

1DLC
3657


ATOM
3534
C
HIS
495
39.964
35.767
47.516
1.00
21.22

1DLC
3558


ATOM
3535
O
HIS
495
40.139
35.531
48.712
1.00
19.11

1DLC
3659


ATOM
3536
CB
HIS
495
38.788
37.953
46.991
1.00
18.90

1DLC
3660


ATOM
3537
CG
HIS
495
39.689
38.498
45.923
1.00
18.38

1DLC
3661


ATOM
3538
ND1
HIS
495
41.018
38.801
46.147
1.00
20.90

1DLC
3662


ATOM
3539
CD2
HIS
495
39.454
38.800
44.624
1.00
19.10

1DLC
3663


ATOM
3540
CE1
HIS
495
41.559
39.261
45.035
1.00
19.17

1DLC
3664


ATOM
3541
NE2
HIS
495
40.631
39.272
44.096
1.00
18.99

1DLC
3665


ATOM
3542
N
LYS
496
40.861
35.489
46.576
1.00
23.22

1DLC
3666


ATOM
3543
CA
LYS
496
42.171
34.876
46.818
1.00
25.84

1DLC
3667


ATOM
3544
C
LYS
496
43.103
35.666
47.755
1.00
26.33

1DLC
3668


ATOM
3545
O
LYS
496
43.986
35.095
48.388
1.00
26.36

1DLC
3669


ATOM
3546
CB
LYS
496
42.853
34.711
45.462
1.00
27.94

1DLC
3670


ATOM
3547
CG
LYS
496
44.251
34.139
45.447
1.00
28.83

1DLC
3671


ATOM
3548
CD
LYS
496
44.885
34.574
44.138
1.00
31.25

1DLC
3672


ATOM
3549
CE
LYS
496
46.050
33.721
43.720
1.00
30.77

1DLC
3673


ATOM
3550
NZ
LYS
496
46.516
34.187
42.380
1.00
37.65

1DLC
3674


ATOM
3551
N
SER
497
42.900
36.977
47.834
1.00
25.35

1DLC
3675


ATOM
3552
CA
SER
497
43.741
37.838
48.660
1.00
22.15

1DLC
3676


ATOM
3553
C
SER
497
43.607
37.644
50.152
1.00
22.22

1DLC
3677


ATOM
3554
O
SER
497
44.460
38.105
50.904
1.00
25.41

1DLC
3678


ATOM
3555
CD
SER
497
43.486
39.306
48.342
1.00
21.23

1DLC
3679


ATOM
3556
OG
SER
497
42.133
39.656
48.583
1.00
22.68

1DLC
3680


ATOM
3557
N
VAL
498
42.526
37.002
50.585
1.00
23.61

1DLC
3681


ATOM
3558
CA
VAL
498
42.293
36.777
52.013
1.00
20.99

1DLC
3682


ATOM
3559
C
VAL
498
43.379
35.909
52.659
1.00
21.85

1DLC
3683


ATOM
3560
O
VAL
498
43.637
34.783
52.229
1.00
23.91

1DLC
3684


ATOM
3561
CB
VAL
498
40.877
36.180
52.285
1.00
21.37

1DLC
3685


ATOM
3562
CG1
VAL
498
40.688
35.932
53.777
1.00
21.12

1DLC
3686


ATOM
3563
CG2
VAL
498
39.788
37.139
51.787
1.00
17.66

1DLC
3687


ATOM
3564
N
ASP
499
44.029
36.467
53.675
1.00
19.96

1DLC
3688


ATOM
3565
CA
ASP
499
45.101
35.801
54.408
1.00
16.56

1DLC
3689


ATOM
3566
C
ASP
499
44.551
35.050
55.623
1.00
17.05

1DLC
3690


ATOM
3567
O
ASP
499
44.184
35.659
56.619
1.00
17.65

1DLC
3691


ATOM
3558
CB
ASP
499
46.145
36.853
54.834
1.00
18.86

1DLC
3692


ATOM
3569
CO
ASP
499
47.238
36.290
55.750
1.00
20.23

1DLC
3693


ATOM
3570
OD1
ASP
499
47.451
35.066
55.786
1.00
28.20

1DLC
3694


ATOM
3571
OD2
ASP
499
47.903
37.079
56.440
1.00
20.77

1DLC
3695


ATOM
3572
N
PHE
500
44.555
33.724
55.561
1.00
18.66

1DLC
3696


ATOM
3573
CA
PHE
500
44.049
32.924
56.668
1.00
21.20

1DLC
3697


ATOM
3574
C
PHE
500
44.725
33.213
57.994
1.00
21.18

1DLC
3698


ATOM
3575
O
PHE
500
44.083
33.205
59.039
1.00
23.89

1DLC
3699


ATOM
3576
CB
PHE
500
44.167
31.416
56.391
1.00
24.40

1DLC
3700


ATOM
3577
CG
PHE
500
43.787
30.552
57.587
1.00
27.73

1DLC
3701


ATOM
3578
CD1
PHE
500
42.445
30.306
57.890
1.00
27.36

1DLC
3702


ATOM
3579
CD2
PHE
500
44.768
30.044
58.445
1.00
26.00

1DLC
3703


ATOM
3580
CE1
PHE
500
42.084
29.578
59.026
1.00
25.15

1DLC
3704


ATOM
3581
CE2
PHE
500
44.417
29.316
59.583
1.00
26.25

1DLC
3705


ATOM
3582
CZ 
PHE
500
43.070
29.084
59.874
1.00
25.99

1DLC
3706


ATOM
3583
N
PHE
501
46.027
33.443
57.959
1.00
21.02

1DLC
3707


ATOM
3584
CA
PHE
501
46.757
33.685
59.191
1.00
21.95

1DLC
3708


ATOM
3585
C
PHE
501
46.673
35.047
59.877
1.00
20.32

1DLC
3709


ATOM
2586
O
PHE
501
47.173
35.189
60.986
1.00
20.00

1DLC
3710


ATOM
3587
CB
PHE
501
48.234
33.285
59.001
1.00
25.51

1DLC
3711


ATOM
3588
CG
PHE
501
48.419
31.823
58.707
1.00
24.22

1DLC
3712


ATOM
3589
CD1
PHE
501
48.383
30.887
59.133
1.00
24.19

1DLC
3713


ATOM
3590
CD2
PHE
501
48.589
31.380
57.403
1.00
25.81

1DLC
3714


ATOM
3591
CE1
PHE
501
48.510
29.536
59.467
1.00
23.35

1DLC
3715


ATOM
3592
CE2
PHE
501
48.717
30.027
57.125
1.00
24.04

1DLC
3716


ATOM
3593
CZ 
PHE
501
48.677
29.104
58.160
1.00
23.29

1DLC
3717


ATOM
3594
N
ASN
502
46.005
36.024
59.256
1.00
21.94

1DLC
3718


ATOM
3595
CA
ANN
502
45.661
37.378
59.828
1.00
18.99

1DLC
3719


ATOM
3596
C
ASN
S02
47.281
37.834
60.228
1.00
19.72

1DLC
3720


ATOM
3597
O
ASN
502
47.530
38.238
61.359
1.00
21.21

1DLC
3721


ATOM
3598
CB
ASN
502
44.959
37.375
61.061
1.00
19.98

1DLC
3722


ATOM
3599
CG
ASN
502
43.470
37.293
60.703
1.00
18.11

1DLC
3723


ATOM
3600
OD1
ASN
502
43.079
37.424
59.544
1.00
34.73

1DLC
3724


ATOM
3601
ND2
ASN
502
42.639
37.089
61.712
1.00
11.25

1DLC
3725


ATOM
3002
N
MET
503
48.197
37.741
59.278
1.00
22.71

1DLC
3726


ATOM
3603
CA
MET
503
49.590
38.071
59.509
1.00
24.59

1DLC
3727


ATOM
3604
C
MET
503
49.958
39.544
59.415
1.00
26.15

1DLC
3728


ATOM
3605
O
MET
503
49.705
40.199
58.402
1.00
24.32

1DLC
3729


ATOM
3606
CB
MET
503
50.456
37.245
58.565
1.00
31.72

1DLC
3730


ATOM
3607
CG
MET
503
51.918
37.179
58.939
1.00
43.44

1DLC
3731


ATOM
3608
SD 
MET
503
52.748
35.901
57.973
1.00
55.24

1DLC
3732


ATOM
3009
CE
MET
503
52.027
34.424
58.732
1.00
51.41

1DLC
3733


ATOM
3610
N
ILE
504
50.583
40.042
60.482
1.00
26.22

1DLC
3734


ATOM
3611
CA
ILE
504
51.026
41.433
60.575
1.00
27.43

1DLC
3735


ATOM
3612
C
ILE
504
52.423
41.578
59.966
1.00
30.21

1DLC
3736


ATOM
3613
O
ILE
504
53.419
41.149
60.557
1.00
31.93

1DLC
3737


ATOM
3614
CB
ILE
504
51.048
41.912
62.050
1.00
25.85

1DLC
3738


ATOM
3615
CG1
ILE
504
49.702
41.626
62.707
1.00
24.52

1DLC
3739


ATOM
3616
CG2
ILE
504
51.336
43.401
62.129
1.00
24.26

1DLC
3740


ATOM
3617
CD1
ILE
504
48.522
42.137
61.919
1.00
25.27

1DLC
3741


ATOM
3618
N
ASP
505
52.483
42.169
58.776
1.00
32.77

1DLC
3742


ATOM
3619
CA
ASP
505
53.740
42.371
58.055
1.00
32.61

1DLC
3743


ATOM
3620
C
ASP
505
54.658
43.366
58.737
1.00
33.24

1DLC
3744


ATOM
3621
O
ASP
505
54.243
44.501
59.034
1.00
37.00

1DLC
3745


ATOM
3622
CB
ASP
505
53.454
42.928
56.629
1.00
33.22

1DLC
3746


ATOM
3623
CO
ASP
505
54.639
42.636
55.715
1.00
35.54

1DLC
3747


ATOM
3624
OD1
ASP
505
55.606
43.413
55.804
1.00
40.96

1DLC
3748


ATOM
3625
OD2
ASP
505
54.612
41.694
54.903
1.00
39.21

1DLC
3749


ATOM
3626
N
SER
506
55.924
43.018
58.910
1.00
33.99

1DLC
3750


ATOM
3627
CA
SER
506
56.916
43.878
59.569
1.00
31.14

1DLC
3751


ATOM
3628
C
SER
506
57.433
45.058
58.753
1.00
26.45

1DLC
3752


ATOM
3629
O
SER
506
58.091
49.932
59.296
1.00
25.94

1DLC
3753


ATOM
3630
CB
SER
506
58.116
43.049
60.035
1.00
35.65

1DLC
3754


ATOM
3631
OG 
SER
506
58.691
42.318
58.955
1.00
38.49

1DLC
3755


ATOM
3632
N
LYS
507
57.181
45.064
57.452
1.00
24.25

1DLC
3756


ATOM
3633
CA
LYS
507
57.653
46.155
56.603
1.00
29.55

1DLC
3757


ATOM
3634
C
LYS
507
56.540
47.011
56.016
1.00
29.60

1DLC
3758


ATOM
3635
O
LYS
507
56.773
48.150
55.611
1.00
30.94

1DLC
3759


ATOM
3636
CB
LYS
507
58.494
45.630
55.435
1.00
34.60

1DLC
3760


ATOM
3637
CC
LYS
507
59.661
44.732
55.793
1.00
44.16

1DLC
3761


ATOM
3638
CD
LYS
507
59.206
43.295
56.004
1.00
54.27

1DLC
3762


ATOM
3639
CE
LYS
507
60.303
42.327
55.603
1.00
60.68

1DLC
3763


ATOM
3640
NZ
LYS
507
60.686
42.532
54.163
1.00
64.19

1DLC
3764


ATOM
3641
N
LYS
508
55.339
46.452
55.942
1.00
28.18

1DLC
3765


ATOM
3642
CA
LYS
508
54.204
47.165
55.364
1.00
24.79

1DLC
3766


ATOM
3643
C
LYS
508
53.175
47.608
56.378
1.00
23.56

1DLC
3767


ATOM
3644
O
LYS
508
53.248
47.273
57.563
1.00
25.61

1DLC
3768


ATOM
3645
CB
LYS
508
53.480
46.273
54.359
1.00
21.88

1DLC
3769


ATOM
3646
CG
LYS
508
54.329
45.804
53.233
1.00
25.15

1DLC
3770


ATOM
3647
CD
LYS
508
53.592
44.816
52.383
1.00
26.67

1DLC
3771


ATOM
3648
CE
LYS
508
54.495
44.343
51.263
1.00
31.83

1DLC
3772


ATOM
3649
NZ
LYS
508
53.858
43.338
50.378
1.00
35.43

1DLC
3773


ATOM
3650
N
ILE
509
52.239
48.413
55.900
1.00
20.91

1DLC
3774


ATOM
3651
CA
ILE
509
51.121
48.837
56.715
1.00
19.88

1DLC
3775


ATOM
3652
C
ILE
509
50.137
47.695
56.446
1.00
19.04

1DLC
3776


ATOM
3653
O
ILE
509
49.887
47.333
55.293
1.00
17.01

1DLC
3777


ATOM
3654
CB
ILE
509
50.539
50.186
56.236
1.00
18.64

1DLC
3778


ATOM
3655
CG3
1ILE
509
51.530
51.317
56.558
1.00
14.90

1DLC
3779


ATOM
3656
CG2
ILE
509
49.157
50.421
56.872
1.00
15.43

1DLC
3780


ATOM
3657
CD1
ILE
509
51.149
52.677
56.007
1.00
11.51

1DLC
3781


ATOM
3658
N
THR
510
49.674
47.052
57.506
1.00
21.46

1DLC
3782


ATOM
3659
CA
THR
510
48.751
45.931
57.358
1.00
20.67

1DLC
3783


ATOM
3660
C
THR
510
47.309
46.291
57.709
1.00
19.90

1DLC
3784


ATOM
3661
O
THR
510
47.034
46.781
58.806
1.00
23.72

1DLC
3785


ATOM
3662
CB
THR
510
49.181
44.726
58.253
1.00
20.85

1DLC
3786


ATOM
3663
CG1
THR
510
50.522
44.326
57.929
1.00
20.93

1DLC
3787


ATOM
3664
CG2
THR
510
48.241
43.541
58.051
1.00
21.70

1DLC
3788


ATOM
3665
N
GLN
511
46.399
46.087
56.763
1.00
18.34

1DLC
3789


ATOM
3666
CA
GLN
511
44.979
46.336
57.001
1.00
16.87

1DLC
3790


ATOM
3667
C
GLN
511
44.283
45.037
57.428
1.00
20.95

1DLC
3791


ATOM
3668
O
GLN
511
44.281
44.048
56.689
1.00
22.60

1DLC
3792


ATOM
3669
CS
GLN
511
44.293
46.868
55.748
1.00
12.52

1DLC
3793


ATOM
3670
CG
GLN
511
44.506
48.332
55.481
1.00
14.00

1DLC
3794


ATOM
3671
CD
GLN
511
43.533
48.867
54.440
1.00
18.99

1DLC
3795


ATOM
3672
OE1
GIN
511
43.290
48.236
53.417
1.00
21.11

1DLC
3796


ATOM
3673
NE2
GLN
511
42.956
50.018
54.708
1.00
19.00

1DLC
3797


ATOM
3674
N
LED
512
43.710
45.043
58.626
1.00
22.52

1DLC
3798


ATOM
3675
CA
LED
512
42.989
43.889
59.162
1.00
21.75

1DLC
3799


ATOM
3676
C
LED
512
41.480
44.130
59.277
1.00
19.63

1DLC
3800


ATOM
3677
O
LEU
512
41.023
44.839
60.175
1.00
19.45

1DLC
3801


ATOM
3678
CB
LEU
512
43.522
43.518
60.546
1.00
25.44

1DLC
3802


ATOM
3679
CG
LED
512
44.431
42.303
60.672
1.00
32.43

1DLC
1803


ATOM
3680
CD1
LEU
512
44.559
41.951
62.148
1.00
32.49

1DLC
3804


ATOM
3681
CD2
LEU
512
43.843
41.128
59.892
1.00
35.48

1DLC
3805


ATOM
3682
N
PRO
513
40.685
43.537
58.372
1.00
17.33

1DLC
3806


ATOM
3683
CA
PRO
513
39.227
43.700
58.402
1.00
16.04

1DLC
3807


ATOM
3684
C
PRO
513
38.669
43.052
59.662
1.00
15.65

1DLC
3808


ATOM
3685
O
PRO
513
39.043
41.933
59.993
1.00
19.58

1DLC
3809


ATOM
3686
CR
PRO
513
38.776
42.934
57.163
1.00
12.95

1DLC
3810


ATOM
3687
CG
PRO
513
39.964
43.017
56.253
1.00
16.06

1DLC
3811


ATOM
3688
CD
PRO
513
41.096
42.757
57.195
1.00
16.99

1DLC
3812


ATOM
3689
N
LED
514
37.775
43.742
60.361
1.00
17.11

1DLC
3813


ATOM
3690
CA
LED
514
37.187
43.195
61.584
1.00
17.00

1DLC
3814


ATOM
3691
C
LEU
514
36.391
41.896
61.390
1.00
16.47

1DLC
3815


ATOM
3692
O
LEU
514
36.222
41.115
62.334
1.00
15.86

1DLC
3816


ATOM
3693
CB
LEU
514
36.324
44.249
62.279
1.00
20.38

1DLC
3817


ATOM
3694
CG
LEU
514
36.962
44.901
63.512
1.00
24.64

1DLC
3818


ATOM
3695
CD1
LEU
514
37.104
43.877
64.633
1.00
22.36

1DLC
3819


ATOM
3696
CD2
LEU 
514
38.319
45.500
63.156
1.00
26.24

1DLC
3820


ATOM
3697
N
VAL 
515
35.888
41.668
60.179
1.00
13.44

1DLC
3821


ATOM
3698
CA
VAL 
515
35.147
40.443
59.906
1.00
17.69

1DLC
3522


ATOM
3699
C
VAL 
515
36.038
39.200
59.983
1.00
19.77

1DLC
3823


ATOM
3700
O
VAL 
515
35.541
38.082
59.927
1.00
21.83

1D1C
3824


ATOM
3701
CB
VAL 
515
34.382
40.476
58.546
1.00
15.76

1DLC
3525


ATOM
3702
CG1
VAL 
515
33.316
41.552
58.564
1.00
15.76

1DLC
3826


ATOM
3703
CG2
VAL 
515
35.326
40.693
57.326
1.00
13.28

1DLC
3827


ATOM
3704
N
LYS 
516
37.351
39.405
60.106
1.00
22.24

1DLC
3828


ATOM
3705
CA
LYS
516
38.311
38.204
60.233
1.00
20.87

1DLC
3829


ATOM
3706
C
LYS 
516
38.405
37.867
61.704
1.00
21.16

1DLC
3830


ATOM
3707
O
LYS 
516
39.164
36.967
62.059
1.00
22.50

1DLC
3831


ATOM
3708
CB
LYS 
516
39.692
38.716
59.717
1.00
19.84

1DLC
3832


ATOM
3709
CG
LYS 
516
39.768
39.001
58.211
1.00
19.10

1DLC
3833


ATOM
3710
CD
LYS
516
39.499
37.756
57.361
1.00
18.48

1DLC
3834


ATOM
3711
CE
LYS
516
40.581
36.692
57.519
1.00
19.98

1DLC
3835


ATOM
3712
NZ
LYS
516
41.938
37.189
57.136
1.00
18.44

1DLC
3836


ATOM
3713
N
ALA
517
37.652
38.534
62.568
1.00
19.22

1DLC
3837


ATOM
3714
CA
ALA
517
37.631
38.173
63.972
1.00
18.13

1DLC
3838


ATOM
3715
C
ALA
517
37.037
36.769
64.075
1.00
15.92

1DLC
3839


ATOM
3716
O
ALA
517
36.396
36.277
63.141
1.00
21.52

1DLC
3840


ATOM
3717
CB
ALA
517
36.782
39.171
64.759
1.00
12.71

1DLC
3841


ATOM
3718
N
TYR
518
37.289
36.093
65.183
1.00
21.01

1DLC
3842


ATOM
3719
CA
TYR
518
36.728
34.759
65.364
1.00
23.07

1DLC
3843


ATOM
3720
C
TYR
518
35.657
34.785
66.451
1.00
24.25

1DLC
3844


ATOM
3721
O
TYR 
518
34.881
33.846
66.592
1.00
28.06

1DLC
1845


ATOM
3722
CB
TYR
518
37.824
33.743
65.716
1.00
19.73

1DLC
3846


ATOM
3723
CG
TYR
518
38.472
33.952
67.065
1.00
19.33

1DLC
3847


ATOM
3724
CD1
TYR 
518
37.888
33.442
68.229
1.00
22.01

1DLC
3848


ATOM
3725
CD2
TYR 
518
39.676
34.644
67.180
1.00
19.85

1DLC
3849


ATOM
3726
CE1
TYR
518
38.485
33.611
69.471
1.00
18.79

1DLC
3650


ATOM
3727
CE2
TYR 
518
40.283
34.823
68.417
1.00
20.61

1DLC
3851


ATOM
3728
CZ 
TYR
518
39.682
34.304
69.557
1.00
22.78

1DLC
3552


ATOM
3729
OH
TYR 
518
40.270
34.493
70.783
1.00
24.17

1DLC
3853


ATOM
3730
N
LYS 
519
35.564
35.905
67.160
1.00
24.18

1DLC
3854


ATOM
3731
CA
LYS
519
34.615
36.027
68.249
1.00
21.87

1DLC
3855


ATOM
3732
C
LYS 
519
34.027
37.429
68.430
1.00
22.52

1DLC
3856


ATOM
3733
O
LYS 
519
34.758
38.410
68.527
1.00
22.87

1DLC
3857


ATOM
3734
CB
LYS 
519
35.328
35.593
69.526
1.00
24.86

1DLC
3858


ATOM
3735
CG
LYS 
519
34.512
35.599
70.783
1.00
31.39

1DLC
3059


ATOM
3736
CD
LYS 
519
35.400
35.210
71.953
1.00
38.43

1DLC
3860


ATOM
3737
CE
LYS 
519
34.616
35.118
73.255
1.00
45.64

1DLC
3861


ATOM
3738
NZ
LYS
519
35.523
34.808
74.400
1.00
49.23

1DLC
3862


ATOM
3739
N
LEU
520
32.703
37.522
68.422
1.00
21.94

1DLC
3863


ATOM
3740
CA
LEU
520
32.024
38.794
68.653
1.00
24.06

1DLC
3864


ATOM
3741
C
LEU 
520
31.408
38.738
70.050
1.00
27.63

1DLC
3865


ATOM
3742
O
LEU 
520
31.091
37.660
70.556
1.00
29.95

1DLC
3866


ATOM
3743
CB
LEU 
520
30.943
39.063
67.600
1.00
20.93

1DLC
3867


ATOM
3744
CG
LEU 
520
31.438
39.461
66.209
1.00
21.24

1DLC
3868


ATOM
3745
CD1
LEU 
520
30.268
39.640
65.274
1.00
21.64

1DLC
3869


ATOM
3746
CD2
LEU
520
32.252
40.744
66.292
1.00
20.28

1DLC
3870


ATOM
3747
N
GLN 
521
31.214
39.894
70.668
1.00
30.71

1DLC
3871


ATOM
3748
CA
GLN
521
30.667
39.935
72.015
1.00
32.68

1DLC
3572


ATOM
3749
C
GLN 
521
29.943
41.237
72.338
1.00
32.85

1DLC
3873


ATOM
3750
O
GLN
521
29.963
42.183
71.554
1.00
33.05

1DLC
3874


ATOM
3751
CB
GLN 
521
31.795
39.681
73.019
1.00
38.17

1DLC
3875


ATOM
3752
CG
GLN 
521
33.040
40.525
72.764
1.00
47.16

1DLC
3876


ATOM
3753
CD
GLN 
521
34.341
39.733
72.860
1.00
50.53

1DLC
3877


ATOM
3754
OE1
GLN 
521
34.416
38.715
73.546
1.00
53.19

1DLC
3878


ATOM
3755
NE2
GLN 
521
35.372
40.205
72.171
1.00
49.13

1DLC
3879


ATOM
3756
N
SER 
522
29.284
41.261
73.494
1.00
34.02

1DLC
3880


ATOM
3757
CA
SER
522
28.529
42.427
73.963
1.00
33.25

1DLC
1881


ATOM
3758
C
SER 
522
27.458
42.871
72.973
1.00
32.49

1DLC
3882


ATOM
3759
O
SER 
522
27.132
44.051
72.887
1.00
34.90

1DLC
3883


ATOM
3760
CB
SER
522
29.464
43.607
74.261
1.00
34.44

1DLC
3884


ATOM
3761
OG
SER
522
30.460
43.269
75.221
1.00
37.23

1DLC
3835


ATOM
3762
N
GLY 
523
26.932
41.931
72.201
1.00
32.83

1DLC
3886


ATOM
3763
CA
GLY
523
25.906
42.283
71.236
1.00
35.47

1DLC
3887


ATOM
3764
C
GLY 
523
26.415
42.914
69.946
1.00
37.76

1DLC
3888


ATOM
3765
O
GLY 
523
25.694
43.676
69.291
1.00
43.56

1DLC
3889


ATOM
3766
N
ALA 
524
27.675
42.662
69.506
1.00
33.37

1DLC
3890


ATOM
3767
CA
ALA
524
28.228
43.181
68.366
1.00
25.62

1DLC
3891


ATOM
3768
C
MA
524
27.772
42.233
67.254
1.00
25.43

1DLC
3892


ATOM
3769
O
ALA
524
27.507
41.054
67.501
1.00
25.41

1DLC
3893


ATOM
3770
CB
ALA
524
29.742
43.232
68.443
1.00
22.42

1DLC
3894


ATOM
3771
N
SER 
525
27.648
42.738
66.035
1.00
24.40

1DLC
3895


ATOM
3772
CA
SER
525
27.224
41.887
64.927
1.00
22.01

1DLC
3896


ATOM
3773
C
SER 
525
27.755
42.326
63.571
1.00
19.44

1DLC
3897


ATOM
3774
O
SER 
525
28.125
43.479
63.380
1.00
21.43

1DLC
3898


ATOM
3775
CB
SER
525
25.702
41.820
64.863
1.00
21.54

1DLC
3899


ATOM
3776
OG
SER 
525
25.147
43.092
64.593
1.00
25.37

1DLC
3900


ATOM
3777
N
VAL 
526
27.797
41.387
62.634
1.00
19.65

1DLC
3901


ATOM
3778
CA
VAL
526
28.261
41.669
61.282
1.00
16.70

1DLC
3902


ATOM
3779
C
VAL 
526
27.096
42.274
60.519
1.00
19.66

1DLC
3903


ATOM
3780
O
VAL 
526
25.985
41.742
60.522
1.00
25.06

1DLC
3904


ATOM
3781
CB
VAL 
526
28.753
40.403
60.562
1.00
14.06

1DLC
3905


ATOM
3782
CG1
VAL 
526
29.368
40.763
59.211
1.00
11.22

1DLC
3906


ATOM
3783
CG2
VAL
526
29.761
39.676
61.436
1.00
14.41

1DLC
3907


ATOM
3784
N
VAL
527
27.365
43.390
59.863
1.00
19.37

1DLC
3908


ATOM
3785
CA
VAL
527
26.361
44.119
59.116
1.00
15.54

1DLC
3909


ATOM
3786
C
VAL 
527
26.834
44.303
57.672
1.00
15.70

1DLC
3910


ATOM
3787
O
VAL
527
28.034
44.247
57.392
1.00
17.61

1DLC
3911


ATOM
3788
CB
VAL 
527
26.098
45.469
59.854
1.00
17.86

1DLC
3912


ATOM
3789
CG1
VAL 
527
25.762
46.576
58.907
1.00
23.79

1DLC
3913


ATOM
3790
CG2
VAL
527
24.983
45.294
60.864
1.00
15.07

1DLC
3914


ATOM
3791
N
ALA
528
25.887
44.454
56.751
1.00
14.37

1DLC
3915


ATOM
3792
CA
ALA
528
25.204
44.644
55.340
1.00
15.60

1DLC
3916


ATOM
3793
C
ALA 
528
27.117
45.844
55.173
1.00
18.07

1DLC
3917


ATOM
3794
O
ALA 
528
26.894
46.890
55.775
1.00
20.56

1DLC
3918


ATOM
3795
CD
ALA
528
24.937
44.838
54.531
1.00
12.04

1DLC
3919


ATOM
3796
N
GLY
529
28.152
45.687
54.361
1.00
18.47

1DLC
3920


ATOM
3797
CA
GLY
529
29.081
46.778
54.165
1.00
19.29

1DLC
3921


ATOM
3798
C
GLY 
529
28.491
47.865
53.305
1.00
19.15

1DLC
3922


ATOM
3799
O
GLY
529
27.583
47.595
52.518
1.00
21.01

1DLC
3923


ATOM
3800
N
PRO
530
29.007
49.101
53.404
1.00
18.13

1DLC
3924


ATOM
3801
CA
PRO
530
28.519
50.239
52.618
1.00
16.51

1DLC
3925


ATOM
3802
C
PRO 
530
28.840
50.175
51.112
1.00
16.39

1DLC
3926


ATOM
3803
O
PRO 
530
28.610
51.139
50.386
1.00
17.87

1DLC
3927


ATOM
3804
CB
PRO
530
29.177
51.434
53.313
1.00
15.38

1DLC
3928


ATOM
3805
CG
PRO
530
30.462
50.873
53.810
1.00
15.73

1DLC
3929


ATOM
3806
CD
PRO 
530
30.048
49.526
54.357
1.00
17.90

1DLC
3930


ATOM
3807
N
ARG 
531
29.347
49.024
50.660
1.00
15.80

1DLC
3931


ATOM
3808
CA
ARG
531
29.705
48.743
49.260
1.00
16.70

1DLC
3932


ATOM
3809
C
ARG 
531
31.048
49.293
48.778
1.00
18.92

1DLC
3933


ATOM
3810
O
ARG 
531
31.478
48.985
47.672
1.00
23.34

1DLC
3934


ATOM
3811
CB
ARG
531
28.603
49.164
48.270
1.00
19.92

1DLC
3935


ATOM
3812
CG
ARG
531
27.162
48.685
48.568
1.00
28.20

1DLC
3936


ATOM
3813
CD
ARG 
531
26.953
47.171
48.469
1.00
31.24

1DLC
3937


ATOM
3814
NE 
ARG 
531
27.509
46.435
49.608
1.00
37.62

1DLC
3938


ATOM
3815
CZ
ARG 
531
26.844
45.526
50.321
1.00
41.22

1DLC
3939


ATOM
3816
NH1
ARG 
531
25.586
45.229
50.024
1.00
43.68

1DLC
3940


ATOM
3817
NH2
ARG
531
27.438
44.914
51.342
1.00
43.63

1DLC
3941


ATOM
3818
N
PHE
532
31.724
50.094
49.593
1.00
19.98

1DLC
3942


ATOM
3819
CA
PHE
532
33.014
50.644
49.175
1.00
18.86

1DLC
3943


ATOM
3820
C
PHE
532
34.203
50.235
50.042
1.00
18.68

1DLC
3944


ATOM
3921
O
PHE
532
35.295
50.766
49.876
1.00
22.14

1DLC
3945


ATOM
3822
CS
PHE
532
32.947
52.174
49.060
1.00
16.92

1DLC
3946


ATOM
3823
CG
PHE
532
32.563
52.873
50.338
1.00
19.17

1DLC
3947


ATOM
3824
CD1
PHE
532
33.496
53.066
51.356
1.00
18.16

1DLC
3948


ATOM
3825
CD2
PHE
532
31.264
53.337
50.527
1.00
15.07

1DLC
3949


ATOM
3826
CE1
PHE
532
33.135
53.708
52.546
1.00
17.02

1DLC
3950


ATOM
3827
CE2
PHE
532
30.898
53.977
51.708
1.00
10.86

1DLC
3951


ATOM
3828
CZ
PHE
532
31.831
54.163
52.719
1.00
15.12

1DLC
3952


ATOM
3829
N
THR
533
33.998
49.284
50.951
1.00
17.51

1DLC
3953


ATOM
3830
CA
THR
533
35.072
48.827
51.839
1.00
14.72

1DLC
3954


ATOM
3831
C
THR
533
35.651
47.437
51.531
1.00
14.62

1DLC
3955


ATOM
3832
O
THR 
533
36.485
46.945
52.279
1.00
16.18

1DLC
3956


ATOM
3833
CB
THR 
533
34.629
48.834
53.316
1.00
13.10

1DLC
3957


ATOM
3834
OG1
THR
533
33.574
47.884
53.498
1.00
17.35

1DLC
3958


ATOM
3835
CG2
THR 
533
34.140
50.210
51.730
1.00
9.08

1DLC
3959


ATOM
3836
N
GLY
534
35.193
46.797
50.457
1.00
13.58

1DLC
3960


ATOM
3837
CA
GLY 
534
35.702
45.480
50.099
1.00
11.66

1DLC
3961


ATOM
1818
C
GLY 
534
35.064
44.293
50.796
1.00
11.74

1DLC
3962


ATOM
3839
O
GLY
534
15.328
43.138
50.460
1.00
10.96

1DLC
3963


ATOM
3840
N
GLY 
535
34.217
44.586
51.776
1.00
14.26

1DLC
3964


ATOM
3841
CA
GLY 
535
33.524
43.554
52.528
1.00
14.95

1DLC
3965


ATOM
3842
C
GLY 
535
32.530
44.107
53.542
1.00
16.62

1DLC
1966


ATOM
3843
O
GLY 
535
32.129
45.269
53.460
1.00
15.43

1DLC
3967


ATOM
3844
N
ASP 
536
32.131
43.283
54.503
1.00
15.04

1DLC
3968


ATOM
3845
CA
ASP
536
31.180
43.722
55.514
1.00
16.74

1DLC
3969


ATOM
3846
C
ASP 
536
31.844
44.387
56.715
1.00
16.82

1DLC
3570


ATOM
3847
O
ASP 
536
33.066
44.423
56.806
1.00
18.08

1DLC
3971


ATOM
3848
CB
ASP 
536
30.265
42.566
55.935
1.00
15.87

1DLC
3972


ATOM
3849
CG
ASP 
536
29.333
42.124
54.811
1.00
19.56

1DLC
3973


ATOM
3850
OD1
ASP
536
28.895
42.978
54.003
1.00
19.60

1DLC
3974


ATOM
3851
OD2
ASP 
536
29.036
40.916
54.724
1.00
21.83

1DLC
3975


ATOM
3852
N
ILE 
537
31.037
44.932
57.621
1.00
15.79

1DLC
3976


ATOM
3853
CA
ILE
537
31.561
45.626
58.791
1.00
15.94

1DLC
3977


ATOM
3854
C
ILE 
537
30.911
45.174
60.094
1.00
19.56

1DLC
3978


ATOM
3855
O
ILE 
537
29.945
44.411
60.080
1.00
21.80

1DLC
3979


ATOM
3856
CB
ILE
537
31.392
47.160
58.659
1.00
17.46

1DLC
3980


ATOM
3857
CG1
ILE
537
29.902
47.537
58.605
1.00
18.41

1DLC
3981


ATOM
3858
CG2
ILE 
537
32.155
47.668
57.436
1.00
16.62

1DLC
3982


ATOM
3859
CD1
ILE
537
29.628
49.004
58.312
1.00
13.27

1DLC
3983


ATOM
3860
N
ILE 
538
31.464
45.619
61.219
1.00
19.15

1DLC
3984


ATOM
3861
CA
ILE 
538
30.929
45.263
62.533
1.00
19.28

1DLC
3985


ATOM
3862
C
ILE 
538
30.189
46.433
63.167
1.00
17.76

1DLC
3986


ATOM
3863
O
ILE 
538
30.687
47.556
63.207
1.00
17.93

1DLC
3987


ATOM
3864
CE
ILE 
538
32.047
44.748
63.506
1.00
20.58

1DLC
3988


ATOM
3665
CG1
ILE 
538
32.256
43.235
63.328
1.00
21.11

1DLC
3989


ATOM
3866
CG2
ILE 
538
31.696
45.055
64.977
1.00
15.08

1DLC
3990


ATOM
3867
CD1
ILE
538
32.758
42.812
61.968
1.00
22.07

1DLC
3991


ATOM
3868
N
GLN 
539
28.978
46.154
63.626
1.00
19.91

1DLC
3992


ATOM
3869
CA
GLN
539
28.139
47.142
64.283
1.00
21.14

1DLC
3993


ATOM
3870
C
GLN
539
28.148
46.929
65.790
1.00
21.70

1DLC
3994


ATOM
3871
O
GLN
539
27.816
45.847
66.273
1.00
23.99

1DLC
3995


ATOM
3872
CB
GLN
539
26.707
47.021
63.780
1.00
25.95

1DLC
3996


ATOM
3873
CG
GLN
539
25.764
48.075
64.333
1.00
30.75

1DLC
3997


ATOM
3874
CD
GLN 
539
24.328
47.810
63.941
1.00
32.55

1DLC
3998


ATOM
3875
OE1
GLN
539
23.816
48.378
62.980
1.00
33.12

1DLC
3999


ATOM
3876
NE2
GLN
539
23.679
46.918
64.669
1.00
34.27

1DLC
4000


ATOM
3877
N
CYS
540
28.528
47.968
66.523
1.00
23.44

1DLC
4001


ATOM
3878
CA
CYS
540
28.564
47.939
67.983
1.00
23.84

1DLC
4002


ATOM
3879
C
CYS
540
27.459
48.828
68.526
1.00
24.50

1DLC
4003


ATOM
3880
O
CYS
540
27.331
49.985
68.133
1.00
26.64

1DLC
4004


ATOM
3881
CB
CYS
540
29.921
48.408
68.505
1.00
20.82

1DLC
4005


ATOM
3882
SG 
CYS
540
31.256
47.385
67.896
1.00
24.17

1DLC
4006


ATOM
3883
N
THR
541
26.640
48.270
69.405
1.00
27.07

1DLC
4007


ATOM
3884
CA
THR
541
25.529
49.019
69.980
1.00
28.11

1DLC
4008


ATOM
3885
C
THR
541
25.593
49.152
71.501
1.00
29.79

1DLC
4009


ATOM
3886
O
THR
541
24.819
49.901
72.088
1.00
34.10

1DLC
4010


ATOM
3887
CB
THR
541
24.165
48.396
69.587
1.00
26.24

1DLC
4011


ATOM
3888
CG1
THR
541
24.060
47.068
70.118
1.00
30.21

1DLC
4012


ATOM
3889
CG2
THR
541
24.022
48.337
68.079
1.00
23.34

1DLC
4013


ATOM
3890
N
GLU
542
26.532
48.459
72.140
1.00
30.44

1DLC
4014


ATOM
3891
CA
GLU
542
26.654
48.529
73.595
1.00
29.89

1DLC
4015


ATOM
3892
C
GLU
542
28.070
48.788
74.082
1.00
29.72

1DLC
4016


ATOM
3893
O
OLD
542
29.038
48.531
73.371
1.00
28.80

1DLC
4017


ATOM
3894
CD
GLU
542
26.137
47.246
74.230
1.00
34.31

1DLC
4018


ATOM
3895
CG
GLU
542
24.633
47.084
74.162
1.00
44.89

1DLC
4019


ATOM
3896
CD
GLU
542
24.195
45.678
74.502
1.00
51.23

1DLC
4020


ATOM
3897
OE1
GLU
542
24.867
45.025
75.332
1.00
56.34

1DLC
4021


ATOM
1898
OE2
GLU
542
23.181
45.218
73.930
1.00
58.74

1DLC
4022


ATOM
3899
N
ASN
543
28.180
49.306
75.299
1.00
30.82

1DLC
4023


ATOM
3900
CA
ASN
543
29.479
49.589
75.894
1.00
33.54

1DLC
4024


ATOM
3901
C
ASN
543
30.123
48.319
76.434
1.00
35.03

1DLC
4025


ATOM
3902
O
ASN
543
29.534
47.626
77.254
1.00
40.96

1DLC
4026


ATOM
3903
CB
ASN
543
29.338
50.595
77.028
1.00
33.74

1DLC
4027


ATOM
3904
CG
ASN
543
29.091
51.994
76.531
1.00
35.64

1DLC
4028


ATOM
3905
OD1
ASN
543
29.652
52.412
75.527
1.00
37.08

1DLC
4029


ATOM
3906
ND2
ASN
543
28.267
52.739
77.245
1.00
39.76

1DLC
4030


ATOM
3907
N
GLY
544
31.326
48.016
75.969
1.00
33.62

1DLC
4031


ATOM
3908
CA
GLY
544
32.029
46.833
76.426
1.00
33.21

1DLC
4032


ATOM
3909
C
GLY
544
32.845
46.227
75.309
1.00
34.24

1DLC
4033


ATOM
3910
O
GLY
544
33.154
46.903
74.328
1.00
34.87

1DLC
4034


ATOM
3911
N
SER
545
33.226
44.964
75.454
1.00
34.84

1DLC
4035


ATOM
3912
CA
SER
545
33.997
44.305
74.402
1.00
37.03

1DLC
4036


ATOM
3913
C
SER
545
33.183
44.282
73.118
1.00
35.99

1DLC
4037


ATOM
3914
O
SER
545
31.978
44.513
73.126
1.00
39.41

1DLC
4038


ATOM
3915
CE
SER
545
34.370
42.873
74.785
1.00
39.43

1DLC
4039


ATOM
3916
OG
SER
545
35.464
42.856
75.677
1.00
47.60

1DLC
4040


ATOM
3917
N
ALA
546
33.835
43.972
72.015
1.00
31.02

1DLC
4041


ATOM
3918
CA
ALA
546
33.133
43.941
70.757
1.00
27.54

1DLC
4042


ATOM
3919
C
ALA
546
33.600
42.772
69.929
1.00
26.24

1DLC
4043


ATOM
3920
O
ALA
546
32.809
41.914
69.551
1.00
27.56

1DLC
4044


ATOM
3921
CB
ALA
546
33.356
45.248
70.012
1.00
28.49

1DLC
4045


ATOM
3922
N
ALA
547
34.905
42.705
69.705
1.00
24.78

1DLC
4046


ATOM
3923
CA
ALA
547
35.471
41.643
68.894
1.00
24.38

1DLC
4047


ATOM
3924
C
ALA
547
36.864
41.231
69.329
1.00
25.97

1DLC
4048


ATOM
3925
O
ALA
547
37.629
42.033
69.874
1.00
26.00

1DLC
4049


ATOM
3926
CB
ALA
547
35.494
42.068
67.427
1.00
19.70

1DLC
4050


ATOM
3927
N
THR
548
37.163
39.955
69.114
1.00
27.03

1DLC
4051


ATOM
3928
CA
THR
548
38.467
39.387
69.419
1.00
24.71

1DLC
4052


ATOM
3929
C
THR
548
38.967
38.779
68.118
1.00
24.86

1DLC
4053


ATOM
3930
O
THR
548
38.313
37.924
67.516
1.00
26.12

1DLC
4054


ATOM
3931
CB
THR
548
38.401
38.296
70.501
1.00
24.53

1DLC
4055


ATOM
3932
CG1
THR
548
37.845
38.849
71.699
1.00
26.86

1DLC
4056


ATOM
3933
CG2
TUR
548
39.805
37.768
70.805
1.00
23.92

1DLC
4057


ATOM
3934
N
ILE
549
40.090
39.293
67.651
1.00
24.94

1DLC
4058


ATOM
3935
CA
ILE
549
40.694
38.836
66.418
1.00
24.02

1DLC
4059


ATOM
3936
C
ILE
549
42.085
38.263
66.693
1.00
23.26

1DLC
4060


ATOM
3937
O
ILE
549
42.839
38.798
67.503
1.00
21.17

1DLC
4061


ATOM
3938
CB
ILE
549
40.730
39.992
65.387
1.00
25.33

1DLC
4062


ATOM
3939
CG1
ILE
549
41.441
39.562
64.104
1.00
26.33

1DLC
4063


ATOM
3940
CG2
ILE
549
41.342
41.241
66.004
1.00
27.68

1DLC
4064


ATOM
3941
CD1
ILE
549
41.136
40.472
62.934
1.00
28.86

1DLC
4065


ATOM
3942
N
TYR
550
42.375
37.116
66.089
1.00
24.17

1DLC
4066


ATOM
3943
CA
TYR
550
43.661
36.461
66.272
1.00
24.37

1DLC
4067


ATOM
3944
C
TYR
550
44.674
37.003
65.272
1.00
26.11

1DLC
4068


ATOM
3945
O
TYR
550
44.429
37.047
64.065
1.00
29.47

1DLC
4069


ATOM
3946
CR 
TYR
550
43.522
34.949
66.131
1.00
25.12

1DLC
4070


ATOM
3947
CG
TYR
550
44.776
34.184
66.470
1.00
24.27

1DLC
4071


ATOM
3948
CD1
TYR
550
45.802
34.041
65.533
1.00
26.12

1DLC
4072


ATOM
3949
CD2
TYR
550
44.932
33.590
67.721
1.00
23.82

1DLC
4073


ATOM
3950
CE1
TYR
550
46.944
33.327
65.827
1.00
22.97

1DLC
4074


ATOM
3951
CE2
TYR
550
46.075
32.869
68.025
1.00
22.49

1DLC
4075


ATOM
3952
CZ 
TYR
550
47.071
32.743
67.073
1.00
23.77

1DLC
4076


ATOM
3953
OH
TYR
550
48.194
32.015
67.361
1.00
31.16

1DLC
4077


ATOM
3954
N
VAL
551
45.836
37.362
65.791
1.00
24.14

1DLC
4078


ATOM
3955
CA
VAL
551
46.893
37.947
64.995
1.00
24.15

1DLC
4079


ATOM
3956
C
VAL
551
48.182
37.117
64.962
1.00
23.16

1DLC
4080


ATOM
3957
O
VAL
551
48.576
36.522
65.962
1.00
23.67

1DLC
4081


ATOM
3958
CB
VAL
551
47.132
39.393
65.500
1.00
21.76

1DLC
4082


ATOM
3959
CG1
VAT. 
551
48.555
39.817
65.337
1.00
27.10

1DLC
4083


ATOM
3960
CG2
VAL
551
46.210
40.334
64.761
1.00
23.25

1DLC
4084


ATOM
3961
N
THR
552
48.810
37.065
63.792
1.00
23.48

1DLC
4085


ATOM
3962
CA
THR
552
50.057
36.324
63.597
1.00
24.21

1DLC
4066


ATOM
3963
C
THR
552
51.219
37.236
63.229
1.00
24.68

1DLC
4087


ATOM
3964
O
THR
552
51.314
37.698
62.096
1.00
25.97

1DLC
4088


ATOM
3965
CB
THR
552
49.928
35.277
62.471
1.00
23.38

1DLC
4089


ATOM
3966
CG1
THR
552
48.951
34.300
62.838
1.00
29.47

1DLC
4090


ATOM
3967
CG2
THR
552
51.251
34.579
62.225
1.00
23.28

1DLC
4091


ATOM
3968
N
PRO
553
52.096
37.548
64.193
1.00
30.06

1DLC
4092


ATOM
3969
CA
PRO
553
53.254
38.416
63.925
1.00
31.84

1DLC
4093


ATOM
3970
C
PRO
553
54.218
37.699
62.977
1.00
33.44

1DLC
4094


ATOM
3971

PRO
553
54.444
36.497
63.123
1.00
32.03

1DLC
4095


ATOM
3972
CB
PRO
553
53.871
38.591
65.313
1.00
32.97

1DLC
4096


ATOM
3973
CO
PRO
553
52.671
38.468
66.241
1.00
33.91

1DLC
4097


ATOM
3974
CD
PRO
553
51.962
37.281
65.637
1.00
32.11

1DLC
4098


ATOM
3975
N
ASP
554
54.758
38.413
61.993
1.00
35.95

1DLC
4099


ATOM
3976
CA
ASP
554
55.676
37.788
61.036
1.00
41.00

1DLC
4100


ATOM
3977
C
ASP
554
57.150
37.717
61.467
1.00
42.22

1DLC
4101


ATOM
3978
O
ASP
554
57.949
37.037
60.829
1.00
46.36

1DLC
4102


ATOM
3979
CB
ASP
554
55.570
38.457
59.660
1.00
43.46

1DLC
4103


ATOM
3980
CO 
ASP
554
56.373
39.740
59.569
1.00
46.10

1DLC
4104


ATOM
3981
OD1
ASP
554
56.390
40.500
60.563
1.00
50.84

1DLC
4105


ATOM
3982
OD2
ASP
554
56.992
39.985
58.509
1.00
45.05

1DLC
4106


ATOM
3983
N
VAL
555
57.524
38.457
62.506
1.00
42.99

1DLC
4107


ATOM
3984
CA
VAL
555
58.904
38.429
62.991
1.00
41.56

1DLC
4108


ATOM
3985
C
VAL
555
58.988
38.030
64.454
1.00
45.35

1DLC
4109


ATOM
3986
O
VAL
555
58.022
38.149
65.208
1.00
46.82

1DLC
4110


ATOM
3987
CB
VAL
555
59.634
39.778
62.809
1.00
36.93

1DLC
4111


ATOM
3989
CG1
VAL
555
59.739
40.121
61.345
1.00
36.03

1DLC
4112


ATOM
3989
CG2
VAL
555
58.936
40.878
63.583
1.00
32.39

1DLC
4113


ATOM
3990
N
SER
556
60.174
37.591
64.854
1.00
48.53

1DLC
4114


ATOM
3991
CA
SER
556
60.434
37.149
66.224
1.00
48.94

1DLC
4115


ATOM
3992
C
SER
556
60.820
38.260
67.211
1.00
46.00

1DLC
4116


ATOM
3993
O
SER
556
60.361
38.265
68.359
1.00
48.54

1DLC
4117


ATOM
3994
CB
SER
556
61.524
36.079
66.189
1.00
52.10

1DLC
4118


ATOM
3995
OG 
SER
556
62.482
36.395
65.177
1.00
57.59

1DLC
4119


ATOM
3996
N
TYR
557
61.669
39.188
66.769
1.00
40.86

1DLC
4120


ATOM
3997
CA
TYR
557
62.129
40.295
67.614
1.00
35.42

1DLC
4121


ATOM
3998
C
TYR
557
61.042
41.301
67.985
1.00
34.52

1DLC
4122


ATOM
3999
O
TYR
557
60.016
41.395
67.316
1.00
35.21

1DLC
4123


ATOM
4000
CB
TYR
557
63.295
41.021
66.956
1.00
30.14

1DLC
4124


ATOM
4001
CO
TYR
557
62.963
41.630
65.615
1.00
27.40

1DLC
4125


ATOM
4002
CD1
TYR
557
62.352
42.886
65.527
1.00
25.94

1DLC
4126


ATOM
4003
CD2
TYR
557
63.288
40.971
64.436
1.00
20.52

1DLC
4127


ATOM
4004
CE1
TYR
557
62.078
43.464
64.301
1.00
24.25

1DLC
4128


ATOM
4005
CE2
TYR
557
63.019
41.542
63.204
1.00
24.51

1DLC
4129


ATOM
4006
CZ
TYR
557
62.414
42.787
63.138
1.00
26.31

1DLC
4130


ATOM
4007
OH
TYR
557
62.135
43.344
61.904
1.00
29.41

1DLC
4131


ATOM
4008
N
SER
558
61.331
42.118
68.991
1.00
33.34

1DLC
4132


ATOM
4009
CA
SER
558
60.395
43.114
69.512
1.00
32.79

1DLC
4133


ATOM
4010
C
SER
558
60.019
44.336
68.656
1.00
31.63

1DLC
4134


ATOM
4011
O
SER
558
60.148
45.481
69.099
1.00
30.68

1DLC
4135


ATOM
4012
CB
SER
558
60.855
43.563
70.904
1.00
35.65

1DLC
4136


ATOM
4013
OG 
SER
558
62.262
43.758
70.943
1.00
41.15

1DLC
4137


ATOM
4014
N
GLN
559
59.524
44.085
67.447
1.00
30.48

1DLC
4138


ATOM
4015
CA
GLN
559
59.077
45.140
66.533
1.00
29.46

1DLC
4139


ATOM
4016
C
GLN
559
57.911
45.942
67.143
1.00
31.04

1DLC
4140


ATOM
4017
O
GLN
559
56.986
45.378
67.738
1.00
26.59

1DLC
4141


ATOM
4018
CB
GLN
559
58.618
44.519
65.213
1.00
30.68

1DLC
4142


ATOM
4019
CG
GLN
559
57.983
45.485
64.227
1.00
30.37

1DLC
4143


ATOM
4020
CD
GLN
559
56.987
46.419
63.591
1.00
30.94

1DLC
4144


ATOM
4021
OE1
GLN
559
58.868
47.634
63.689
1.00
33.08

1DLC
4145


ATOM
4022
NE2
GLN
559
59.984
45.854
62.933
1.00
32.16

1DLC
4146


ATOM
4023
N
LYS
560
57.983
47.262
67.003
1.00
32.69

1DLC
4147


ATOM
4024
CA
LYS
560
56.959
48.156
67.521
1.00
32.07

1DLC
4148


ATOM
4025
C
LYS
560
56.011
48.599
66.419
1.00
28.30

1DLC
4149


ATOM
4026
O
LYS
560
56.401
48.725
65.256
1.00
23.65

1DLC
4150


ATOM
4027
CB
LYS
560
57.593
49.380
68.186
1.00
37.57

1DLC
4151


ATOM
4028
CG
LYS
560
58.226
49.100
69.538
1.00
44.56

1DLC
4152


ATOM
4029
CD
LYS
560
59.281
50.154
69.855
1.00
55.46

1DLC
4153


ATOM
4030
CE
LYS
560
58.671
51.528
70.103
1.00
59.12

1DLC
4154


ATOM
4031
NE 
LYS
560
58.034
51.582
71.456
1.00
66.07

1DLC
4155


ATOM
4032
N
TYR
561
54.762
48.833
66.816
1.00
28.00

1DLC
4156


ATOM
4033
CA
TYR
561
53.694
49.255
65.919
1.00
24.77

1DLC
4157


ATOM
4034
C
TYR
551
52.616
50.369
66.469
1.00
24.89

1DLC
4158


ATOM
4035
O
TYR
561
52.771
50.628
67.675
1.00
25.20

1DLC
4159


ATOM
4036
CB
TYR
561
52.768
48.073
65.623
1.00
22.54

1DLC
4160


ATOM
4037
CG
TYR
561
53.442
46.903
64.956
1.00
21.90

1DLC
4161


ATOM
4038
CD1
TYR
561
54.015
45.881
65.714
1.00
19.30

1DLC
4162


ATOM
4039
CD2
TYR
561
53.500
46.812
63.566
1.00
15.01

1DLC
4163


ATOM
4040
CE1
TYR
561
54.627
44.801
65.103
1.00
19.55

1DLC
4164


ATOM
4041
CE2
TYR
561
54.109
45.742
62.950
1.00
16.21

1DLC
4165


ATOM
4042
CZ 
TYR
561
54.666
44.736
63.722
1.00
20.28

1DLC
4166


ATOM
4043
OH
TYR
561
55.240
43.642
63.107
1.00
33.74

1DLC
4167


ATOM
4044
N
ARG
562
52.153
51.050
65.544
1.00
25.77

1DLC
4168


ATOM
4045
CA
ARG
562
51.179
52.094
65.654
1.00
23.64

1DLC
4169


ATOM
4046
C
ARG
562
49.907
51.506
65.251
1.00
23.48

1DLC
4170


ATOM
4047
O
ARG
562
49.960
50.823
54.216
1.00
20.35

1DLC
4171


ATOM
4048
CB
ARG
562
51.484
53.414
65.132
1.00
22.03

1DLC
4172


ATOM
4049
CG
ARC
562
52.666
54.190
65.655
1.00
30.26

1DLC
4173


ATOM
4050
CD
ARO
562
52.432
54.744
67.051
1.00
32.80

1DLC
4174


ATOM
4051
NE
ARG
562
51.345
55.719
67.109
1.00
39.02

1DLC
4175


ATOM
4052
CZ
ARG
562
51.269
56.825
66.372
1.00
40.34

1DLC
4176


ATOM
4053
NH1
ARG
562
52.217
57.124
65.494
1.00
42.09

1DLC
4177


ATOM
4054
NH2
ARG
562
50.237
57.645
66.521
1.00
42.48

1DLC
4178


ATOM
4055
N
ALA
563
48.773
51.741
65.894
1.00
22.02

1DLC
4179


ATOM
4056
CA
ALA
563
47.515
51.235
65.378
1.00
18.79

1DLC
4180


ATOM
4057
C
ALA
563
46.629
52.386
64.933
1.00
18.02

1DLC
4181


ATOM
4058
O
ALA
563
46.640
53.461
65.525
1.00
20.34

1DLC
4182


ATOM
4059
CB
ALA
563
46.800
50.392
66.440
1.00
18.24

1DLC
4183


ATOM
4060
N
ARG
564
45.908
52.159
63.846
1.00
18.32

1DLC
4184


ATOM
4061
CA
ARG
564
44.960
53.118
63.290
1.00
16.43

1DLC
4185


ATOM
4062
C
ARG
564
43.631
52.379
63.170
1.00
18.85

1DLC
4186


ATOM
4063
O
ARO
564
43.602
51.185
62.858
1.00
17.80

1DLC
4187


ATOM
4064
CB
ARG
564
45.338
53.481
61.874
1.00
15.45

1DLC
4188


ATOM
4065
CG
ARG
564
46.236
54.635
61.654
1.00
14.12

1DLC
4189


ATOM
4066
CD
ARG
564
46.452
54.611
60.165
1.00
18.52

1DLC
4190


ATOM
4067
NE
ARG
564
47.230
55.713
59.648
1.00
20.74

1DLC
4191


ATOM
4068
CZ
ARG
564
47.640
55.791
58.390
1.00
18.32

1DLC
4192


ATOM
4069
NH1
ARG
564
47.359
54.825
57.523
1.00
13.13

1DLC
4193


ATOM
4070
NH2
ARG
564
48.288
56.872
57.998
1.00
26.68

1DLC
4194


ATOM
4071
N
ILE
565
42.527
53.092
63.319
1.00
18.95

1DLC
4195


ATOM
4072
CA
ILE
565
41.238
52.440
63.187
1.00
17.58

1DLC
4196


ATOM
4073
C
ILE
565
40.301
53.192
62.229
1.00
19.97

1DLC
4197


ATOM
4074
O
ILE
565
40.261
54.430
62.223
1.00
20.07

1DLC
4198


ATOM
4075
CB
ILE
565
40.612
52.176
64.579
1.00
14.60

1DLC
4199


ATOM
4076
CG1
ILE
565
39.335
51.353
64.448
1.00
16.02

1DLC
4200


ATOM
4077
CG2
ILE
565
40.402
53.475
65.331
1.00
15.20

1DLC
4201


ATOM
4078
CD1
ILE
565
38.980
50.629
69.727
1.00
16.53

1DLC
4202


ATOM
4079
N
HIS
566
39.695
52.438
61.307
1.00
18.25

1DLC
4203


ATOM
4080
CA
HIS
566
38.752
52.981
60.329
1.00
14.18

1DLC
4204


ATOM
4081
C
HIS
566
37.366
52.640
60.859
1.00
15.68

1DLC
4205


ATOM
4082
O
HIS
566
36.950
51.482
60.816
1.00
16.47

1DLC
4206


ATOM
4083
CB
HIS
566
38.960
52.341
58.958
1.00
11.65

1DLC
4207


ATOM
4084
CG
HIS
566
38.314
53.093
57.831
1.00
11.11

1DLC
4208


ATOM
4085
ND1
HIS
566
37.635
52.465
56.808
1.00
11.16

1DLC
4209


ATOM
4086
CD2
HIS
566
38.258
54.418
57.558
1.00
11.95

1DLC
4210


ATOM
4087
CE1
HIS
566
31.191
53.366
55.951
1.00
8.58

1DLC
4211


ATOM
4088
NE2
HIS
566
37.554
54.561
56.383
1.00
13.33

1DLC
4212


ATOM
4089
N
TYR
567
36.654
53.654
61.339
1.00
16.40

1DLC
4213


ATOM
4090
CA
TYR
567
35.326
53.471
61.935
1.00
17.25

1DLC
4214


ATOM
4091
C
TYR
567
34.356
54.630
61.612
1.00
17.40

1DLC
4215


ATOM
4092
O
TYR
567
34.730
55.628
60.982
1.00
17.78

1DLC
4216


ATOM
4093
CB
TYR
567
35.485
53.406
63.471
1.00
13.75

1DLC
4217


ATOM
4094
CG
TYR
567
35.831
54.771
64.026
1.00
17.11

1DLC
4218


ATOM
4095
CD1
TYR
567
37.075
55.356
63.767
1.00
16.44

1DLC
4219


ATOM
4096
CD2
TYR
567
34.866
55.549
64.674
1.00
18.59

1DLC
4220


ATOM
4097
CE1
TYR
567
37.341
56.675
64.121
1.00
14.77

1DLC
4221


ATOM
4098
CE2
TYR
567
35.129
56.872
65.033
1.00
14.24

1DLC
4222


ATOM
4099
CZ
TYR
567
36.365
57.423
64.751
1.00
12.88

1DLC
4223


ATOM
4100
OH
TYR
567
36.624
58.727
65.094
1.00
18.70

1DLC
4224


ATOM
4101
N
ALA
568
33.128
54.491
62.114
1.00
15.14

1DLC
4225


ATOM
4102
CA
ALA
568
32.062
55.486
61.997
1.00
11.71

1DLC
4226


ATOM
4103
C
ALA
569
31.335
55.432
63.347
1.00
13.73

1DLC
4221


ATOM
4104
O
ALA
568
31.115
54.349
63.895
1.00
14.98

1DLC
4228


ATOM
4105
CB
ALA
568
31.119
55.140
60.872
1.00
8.00

1DLC
4229


ATOM
4106
N
SER
569
31.010
56.588
63.913
1.00
12.74

1DLC
4230


ATOM
4107
CA
SER
569
30.344
56.623
65.209
1.00
13.22

1DLC
4231


ATOM
4108
C
SER
569
29.342
57.768
65.333
1.00
19.84

1DLC
4232


ATOM
4109
O
SER
569
29.544
58.847
64.767
1.00
23.01

1DLC
4233


ATOM
4110
CB
SER
569
31.384
56.751
66.322
1.00
10.39

1DLC
4214


ATOM
4111
OG
SER
569
30.781
56.784
67.602
1.00
12.68

1DLC
4235


ATOM
4112
N
THR
570
28.262
57.530
66.075
1.00
20.82

1DLC
4236


ATOM
4113
CA
THR
570
27.246
58.561
66.302
1.00
22.66

1DLC
4237


ATOM
4114
C
TAR
570
27.608
59.465
67.494
1.00
24.67

1DLC
4238


ATOM
4115
O
THR
570
26.978
60.496
67.720
1.00
26.92

1DLC
4239


ATOM
4116
CB
THR
570
25.842
57.957
66.517
1.00
19.64

1DLC
4240


ATOM
4117
OG1
THR
570
25.870
57.024
67.602
1.00
17.72

1DLC
4241


ATOM
4118
CG2
THR
570
25.384
57.248
65.262
1.00
18.85

1DLC
4242


ATOM
4119
N
SER
571
28.646
59.085
68.237
1.00
26.33

1DLC
4243


ATOM
4120
CA
SER
571
29.107
59.869
69.186
1.00
26.65

1DLC
4244


ATOM
4121
C
SER
571
30.614
59.783
69.597
1.00
27.37

1DLC
4245


ATOM
4122
O
SER
571
31.309
59.001
68.942
1.00
26.89

1DLC
4246


ATOM
4123
CB
SER
571
28.437
59.388
70.677
1.00
28.07

1DLC
4247


ATOM
4124
OG
SEA
571
29.047
58.203
71.173
1.00
26.73

1DLC
4248


ATOM
4125
N
GLN
572
31.113
60.621
70.502
1.00
29.31

1DLC
4249


ATOM
4126
CA
GLN
572
32.520
60.596
70.871
1.00
27.70

1DLC
4250


ATOM
4127
C
GLN
572
32.645
59.287
71.646
1.00
25.42

1DLC
4251


ATOM
4128
O
GLN
572
31.771
58.935
72.444
1.00
25.29

1DLC
4252


ATOM
4129
CB
GLN
572
32.891
61.789
71.763
1.00
31.54

1DLC
4253


ATOM
4130
CG
GLN
572
32.791
63.161
71.076
1.00
40.28

1DLC
4254


ATOM
4131
CD
GLN
572
33.796
64.189
71.616
1.00
45.09

1DLC
4255


ATOM
4132
OE1
GLN
572
34.886
64.347
71.064
1.00
49.91

1DLC
4256


ATOM
4133
NE2
GLN
572
33.428
64.892
72.685
1.00
44.38

1DLC
4257


ATOM
4134
N
ILE
573
33.702
58.543
71.379
1.00
25.62

1DLC
4258


ATOM
4135
CA
ILE
573
33.891
57.252
72.027
1.00
24.87

1DLC
4259


ATOM
4136
C
ILE
573
35.318
56.964
72.451
1.00
23.49

1DLC
4260


ATOM
4137
O
ILE
573
36.244
57.724
72.165
1.00
24.22

1DLC
4261


ATOM
4138
CB
ILE
573
33.472
56.120
71.084
1.00
24.02

1DLC
4262


ATOM
4139
CG1
ILE
573
34.175
56.308
69.731
1.00
20.45

1DLC
4263


ATOM
4140
CG2
ILE
573
31.954
56.080
70.962
1.00
23.19

1DLC
4264


ATOM
4141
CD1
ILE
573
33.929
55.210
68.750
1.00
21.25

1DLC
4265


ATOM
4142
N
THR
574
35.477
55.856
73.156
1.00
21.66

1DLC
4266


ATOM
4143
CA
THR
574
36.786
55.424
73.591
1.00
L9.94

1DLC
4267


ATOM
4144
C
THR
574
36.991
54.009
73.106
1.00
21.16

1DLC
4268


ATOM
4145
O
THR
574
36.142
53.140
73.300
1.00
20.88

1DLC
4269


ATOM
4146
CB
THR
574
36.936
55.453
75.123
1.00
21.34

1DLC
4270


ATOM
4147
OG1
THR
574
36.902
56.608
75.579
1.00
27.16

1DLC
4271


ATOM
4148
CG2
THR
574
38.251
54.835
75.549
1.00
18.62

1DLC
4272


ATOM
4149
N
PHE
575
38.085
53.806
72.392
1.00
21.90

1DLC
4273


ATOM
4150
CA
PHE
575
38.433
52.408
71.904
1.00
21.69

1DLC
4274


ATOM
4151
C
PRE
575
39.556
51.976
72.801
1.00
22.38

1DLC
4275


ATOM
4152
O
PHE
575
40.441
52.741
73.185
1.00
24.96

1DLC
4276


ATOM
4153
CB
PHE
575
38.904
52.557
70.447
1.00
22.02

1DLC
4277


ATOM
4154
CG
PHE
575
37.782
52.563
69.433
1.00
22.92

1DLC
4278


ATOM
4155
CD1
PHE
575
36.741
51.637
69.514
1.00
23.97

1DLC
4279


ATOM
4156
CD2
PHE
575
37.792
53.462
68.370
1.00
22.78

1DLC
4280


ATOM
4157
CE1
PHE
575
35.729
51.604
68.550
1.00
23.30

1DLC
4281


ATOM
4158
CE2
PHE
575
36.765
53.438
67.402
1.00
24.47

1DLC
4282


ATOM
4159
CZ
PHE
575
35.751
52.502
67.495
1.00
22.95

1DLC
4283


ATOM
4160
N
THE
576
39.470
50.715
73.208
1.00
22.42

1DLC
4284


ATOM
4161
CA
THR
576
40.508
50.112
74.046
1.00
23.02

1DLC
4285


ATOM
4162
C
THR
576
41.004
48.841
73.362
1.00
26.73

1DLC
4286


ATOM
4163
O
THR
576
40.217
46.083
72.775
1.00
27.65

1DLC
4287


ATOM
4164
CB
THR
576
40.005
49.761
75.472
1.00
22.77

1DLC
4288


ATOM
4165
CG1
THE
576
39.490
50.938
76.107
1.00
22.85

1DLC
4289


ATOM
4166
CG2
THR
576
41.151
49.218
76.329
1.00
20.19

1DLC
4290


ATOM
4167
N
LED
577
42.322
48.661
73.364
1.00
26.31

1DLC
4291


ATOM
4168
CA
LED
577
42.952
47.491
72.762
1.00
23.97

1DLC
4292


ATOM
4169
C
LEO
577
43.588
46.622
73.834
1.00
22.18

1DLC
4293


ATOM
4170
O
LEO
577
44.242
47.119
74.752
1.00
22.92

1DLC
4294


ATOM
4171
CB
LEO
577
44.018
47.900
71.744
1.00
21.75

1DLC
4295


ATOM
4172
CG
LEO 
577
43.586
48.805
70.592
1.00
22.22

1DLC
4296


ATOM
4173
CD1
LEU
577
44.732
49.008
69.614
1.00
20.22

1DLC
4297


ATOM
4174
CD2
LEU
577
42.401
48.193
69.894
1.00
22.18

1DLC
4298


ATOM
4175
N
SER
578
43.367
45.321
73.721
1.00
22.27

1DLC
4299


ATOM
4176
CA
SER
578
43.926
44.365
74.660
1.00
22.35

1DLC
4300


ATOM
4177
C
SER
578
44.578
43.224
73.907
1.00
23.31

1DLC
4301


ATOM
4178
O
SER
578
44.143
42.859
72.814
1.00
23.83

1DLC
4302


ATOM
4179
CB
SER
578
42.839
43.784
75.564
1.00
21.54

1DLC
4303


ATOM
4180
OG
SER
578
42.197
44.801
76.303
1.00
25.56

1DLC
4304


ATOM
4181
N
LEO
579
45.659
42.708
74.475
1.00
23.36

1DLC
4305


ATOM
4182
CA
LEU
579
46.371
41.573
73.910
1.00
23.41

1DLC
4306


ATOM
4183
C
LEU
579
46.271
40.490
74.968
1.00
23.47

1DLC
4307


ATOM
4184
O
LEU
579
46.635
40.709
76.124
1.00
21.83

1DLC
4308


ATOM
4185
CB
LEU
579
47.836
41.907
73.655
1.00
25.86

1DLC
4309


ATOM
4186
CG
LEU
579
48.258
42.090
72.203
1.00
30.80

1DLC
4310


ATOM
4187
CD1
LEU
579
49.782
42.146
72.138
1.00
31.83

1DLC
4311


ATOM
4188
CD2
LEU
579
47.730
40.932
71.362
1.00
31.68

1DLC
4312


ATOM
4189
N
ASP
580
45.594
39.357
74.592
1.00
23.35

1DLC
4313


ATOM
4190
CA
ASP
580
45.514
38.243
75.512
1.00
22.65

1DLC
4314


ATOM
4191
C
ASP
580
44.902
38.664
76.853
1.00
21.10

1DLC
4315


ATOM
4192
O
ASP
580
45.335
38.238
77.917
1.00
22.53

1DLC
4316


ATOM
4193
CB
ASP
580
46.832
37.474
75.698
1.00
26.17

1DLC
4117


ATOM
4194
CG
ASP
580
47.291
36.765
74.416
1.00
31.25

1DLC
4318


ATOM
4195
CG1
ASP
580
46.497
36.658
73.459
1.00
33.31

1DLC
4319


ATOM
4196
OD2
ASP
580
48.450
36.303
74.359
1.00
36.06

1DLC
4320


ATOM
4197
N
GLY
581
43.917
39.552
76.786
1.00
21.32

1DLC
4321


ATOM
4198
CA
GLY
581
43.227
40.002
77.981
1.00
21.27

1DLC
4322


ATOM
4199
C
GLY
581
43.824
41.150
78.764
1.00
22.88

1DLC
4323


ATOM
4200
O
GLY
581
43.290
41.536
79.805
1.00
25.91

1DLC
4324


ATOM
4201
N
ALA
582
44.931
41.698
'18.291
1.00
23.56

1DLC
4325


ATOM
4202
CA
ALA
582
45.571
42.810
78.985
1.00
21.79

1DLC
4326


ATOM
4203
C
ALA
582
45.518
44.085
78.136
1.00
22.18

1DLC
4327


ATOM
4204
O
ALA
582
45.914
44.083
76.965
1.00
23.55

1DLC
4328


ATOM
4205
CB
ALA
582
47.005
42.451
79.323
1.00
19.42

1DLC
4329


ATOM
4206
N
PRO
581
44.975
45.177
78.698
1.00
21.27

1DLC
4330


ATOM
4207
CA
PRO
583
44.875
46.448
77.971
1.00
21.05

1DLC
4331


ATOM
4208
C
PRO
583
46.252
47.058
77.716
1.00
22.08

1DLC
4332


ATOM
4209
O
PRO
583
47.119
47.046
78.592
1.00
23.88

1DLC
4333


ATOM
4210
CR
PRO
583
44.089
47.344
78.939
1.00
19.25

1DLC
4334


ATOM
4211
CG
PRO
583
43.411
46.393
79.873
1.00
18.79

1DLC
4335


ATOM
4212
CD
PRO
583
44.427
45.310
80.059
1.00
20.08

1DLC
4336


ATOM
4213
N
PHE
584
46.462
47.585
76.522
1.00
20.46

1DLC
4337


ATOM
4214
CA
PHE
584
47.734
48.217
76.232
1.00
22.26

1DLC
4338


ATOM
4215
C
PHE
584
47.560
49.576
75.572
1.00
24.61

1DLC
4339


ATOM
4216
O
PHE
584
48.451
50.416
75.608
1.00
29.88

1DLC
4340


ATOM
4217
CB
PHE
584
48.622
47.308
75.381
1.00
17.78

1DLC
4341


ATOM
4218
CG
PHE
584
48.113
47.075
73.992
1.00
16.94

1DLC
4342


ATOM
4219
CD1
PHE
584
48.482
47.921
72.954
1.00
15.22

1DLC
4343


ATOM
4220
CD2
PHE
584
47.313
45.981
73.710
1.00
12.59

1DLC
4344


ATOM
4221
CE1
PHE
584
48.067
47.678
71.666
1.00
16.40

1DLC
4345


ATOM
4222
CE2
PHE
584
46.894
45.730
72.420
1.00
16.89

1DLC
4346


ATOM
4223
CZ
PHE
584
47.272
46.578
71.391
1.00
17.05

1DLC
4347


ATOM
4224
N
ASN
585
46.399
49.799
74.981
1.00
25.77

1DLC
4348


ATOM
4225
CA
ASN
585
46.138
51.064
74.319
1.00
27.68

1DLC
4349


ATOM
4226
C
ASN
585
44.688
51.488
74.531
1.00
28.54

1DLC
4350


ATOM
4227
O
ASN
585
43.770
50.671
74.499
1.00
30.79

1DLC
4351


ATOM
4228
CE
ASN
585
46.433
50.944
72.822
1.00
30.11

1DLC
4352


ATOM
4229
CG
ASN
585
47.358
52.038
72.310
1.00
31.24

1DLC
4353


ATOM
4230
OD1
ASN
585
47.347
53.171
72.796
1.00
36.32

1DLC
4354


ATOM
4231
ND2
ASN
585
48.145
51.709
71.303
1.00
34.47

1DLC
4355


ATOM
4232
N
GLN
586
44.494
52.764
74.812
1.00
27.87

1DLC
4356


ATOM
4233
CA
GLN
586
43.161
53.304
75.010
1.00
28.50

1DLC
4357


ATOM
4234
C
GLN
585
43.216
54.725
'14.525
1.00
27.04

1DLC
4358


ATOM
4235
O
GLN
586
44.153
55.445
74.850
1.00
29.74

1DLC
4359


ATOM
4236
CB
GLN 
566
42.782
53.287
76.485
1.00
29.22

1DLC
4360


ATOM
4237
CG
GLN 
586
41.398
53.806
76.740
1.00
29.84

1DLC
4361


ATOM
4238
CD
GLN 
586
41.013
53.713
78.189
1.00
34.57

1DLC
4362


ATOM
4239
OE1
GLN 
586
41.628
54.350
79.047
1.00
35.42

1DLC
4363


ATOM
4240
NE2
GLN 
586
40.001
52.908
78.481
1.00
35.86

1DLC
4364


ATOM
4241
N
TYR 
587
42.239
55.131
73.730
1.00
25.37

1DLC
4365


ATOM
4242
CA
TYR 
587
42.248
56.492
73.222
1.00
26.60

1DLC
4366


ATOM
4243
C
TYR 
587
40.850
57.033
72.971
1.00
25.35

1DLC
4367


ATOM
4244
O
TYR 
587
19.871
56.292
72.967
1.00
26.48

1DLC
4368


ATOM
4245
CB
TYR 
587
43.087
56.569
71.940
1.00
24.36

1DLC
4369


ATOM
4246
CO 
TYR 
587
43.718
57.923
71.683
1.00
23.54

1DLC
4370


ATOM
4247
CD1
TYR 
587
44.469
58.558
72.669
1.00
26.89

1DLC
4371


ATOM
4248
CD2
TYR 
587
43.599
58.551
70.443
1.00
23.40

1DLC
4372


ATOM
4249
CE1
TYR 
587
45.093
59.781
72.427
1.00
26.78

1DLC
4373


ATOM
4250
CE2
TYR 
587
44.217
59.774
70.191
1.00
24.34

1DLC
4374


ATOM
4251
CZ
TYR 
587
44.966
60.379
71.190
1.00
26.40

1DLC
4375


ATOM
4252
OH
TYR 
587
45.616
61.567
70.954
1.00
29.54

1DLC
4376


ATOM
4253
N
TYR 
588
40.777
58.341
72.782
1.00
26.44

1DLC
4377


ATOM
4254
CA
TYR 
588
39.521
59.022
72.524
1.00
27.44

1DLC
4378


ATOM
4255
C
TYR 
588
39.356
59.223
71.016
1.00
26.50

1DLC
4379


ATOM
4256
O
TYR 
588
40.129
59.529
70.320
1.00
23.62

1DLC
4380


ATOM
4257
CS
TYR 
588
39.524
60.372
73.218
1.00
33.96

1DLC
4381


ATOM
4258
CG
TYR 
588
39.899
60.333
74.685
1.00
47.28

1DLC
4382


ATOM
4259
CD
TYR 
588
41.220
60.098
75.091
1.00
53.44

1DLC
4383


ATOM
4260
CD
TYR 
588
38.949
60.612
75.668
1.00
54.01

1DLC
4384


ATOM
4261
CE1
TYR 
588
41.583
60.150
76.443
1.00
58.54

1DLC
4185


ATOM
4262
CE2
TYR 
588
39.297
60.670
77.018
1.00
60.11

1DLC
4386


ATOM
4263
CZ
TYR 
588
40.613
60.443
77.404
1.00
61.86

1DLC
4387


ATOM
4264
OH 
TYR 
588
40.941
60.543
78.746
1.00
65.13

1DLC
4388


ATOM
4265
N
PHE
589
38.132
59.026
70.518
1.00
25.50

1DLC
4389


ATOM
4266
CA
PHE
589
37.821
59.174
69.089
1.00
23.66

10LC
4390


ATOM
4267
C
PHE
589
36.558
59.994
68.795
1.00
22.64

1DLC
4391


ATOM
4268
O
PHE
589
35.549
59.901
69.493
1.00
23.58

1DLC
4392


ATOM
4269
CB
PHE
589
37.763
57.803
68.414
1.00
22.61

1DLC
4393


ATOM
4270
CG
PHE
589
39.078
57.071
68.446
1.00
24.27

1DLC
4394


ATOM
4271
CD1
PHE
589
39.422
56.279
69.537
1.00
24.25

1DLC
4395


ATOM
4272
CD2
PHE
589
39.991
57.207
67.408
1.00
22.86

1DLC
4396


ATOM
4273
CE1
PHE
589
40.658
55.638
69.592
1.00
23.24

1DLC
4397


ATOM
4274
CE2
PRE 
589
41.229
56.566
67.460
1.00
22.86

1DLC
4398


ATOM
4275
CZ 
PEE 
589
41.559
55.784
68.551
1.00
19.36

1DLC
4399


ATOM
4276
N
ASP 
589
36.629
60.800
67.749
1.00
20.80

1DLC
4400


ATOM
4277
CA
ASP 
590
35.522
61.668
67.374
1.00
21.27

1DLC
4401


ATOM
4278
C
ASP
590
34.286
61.011
66.776
1.00
23.02

1DLC
4402


ATOM
4279
O
ASP
590
34.339
59.922
66.206
1.00
24.31

1DLC
4403


ATOM
4280
CB
ASP 
590
36.006
62.740
66.395
1.00
20.90

1DLC
4404


ATOM
4281
CG
ASP 
590
37.235
63.476
66.887
1.00
21.49

1DLC
4405


ATOM
4282
OD1
ASP 
590
37.310
53.822
68.089
1.00
24.77

1DLC
4406


ATOM
4283
OD2
ASP 
590
38.135
63.704
66.058
1.00
25.71

1DLC
4407


ATOM
4284
N
LYS 
591
33.170
61.722
66.905
1.00
25.19

1DLC
4408


ATOM
4285
CA
LYS 
591
31.881
61.318
66.352
1.00
23.03

1DLC
4409


ATOM
4286
C
LYS 
591
31.970
61.618
64.846
1.00
22.08

1DLC
4410


ATOM
4287
O
LYS 
591
32.554
62.629
64.445
1.00
22.29

1DLC
4411


ATOM
4288
CS 
LYS 
591
30.784
62.162
67.007
1.00
25.59

1DLC
4412


ATOM
4289
CG
LYS 
591
29.517
62.378
66.194
1.00
27.04

1DLC
4413


ATOM
4290
CD
LYS 
591
28.657
63.423
66.891
1.00
32.39

1DLC
4414


ATOM
4291
CE
LYS 
591
27.559
63.969
65.997
1.00
33.92

1DLC
4415


ATOM
4292
NZ
LYS 
591
26.505
62.953
65.788
1.00
40.85

1DLC
4416


ATOM
4293
N
THR 
592
31.460
60.726
64.008
1.00
20.63

1DLC
4417


ATOM
4294
CA
THR 
592
31.532
60.961
62.567
1.00
21.77

1DLC
4418


ATOM
4295
C
THR 
592
30.182
61.124
61.878
1.00
24.80

1DLC
4419


ATOM
4296
O
THR
592
30.114
61.669
60.778
1.00
27.91

1DLC
4420


ATOM
4297
CB
THR
592
32.326
59.855
61.832
1.00
20.67

1DLC
4421


ATOM
4298
CG1
THR
592
31.636
58.602
61.933
1.00
18.07

1DLC
4422


ATOM
4299
CG2
TSR
592
33.715
59.716
62.428
1.00
20.53

1DLC
4413


ATOM
4300
N
ILE
593
29.113
60.643
62.510
1.00
23.91

1DLC
4424


ATOM
4301
CA
ILE
593
27.780
60.741
61.922
1.00
23.00

1DLC
4425


ATOM
4302
C
ILE
593
26.700
51.002
62.955
1.00
25.03

1DLC
4426


ATOM
4303
O
TLE
593
26.926
60.868
64.156
1.00
24.13

1DLC
4427


ATOM
4304
CB
ILE
593
27.362
59.431
61.185
1.00
20.64

1DLC
4428


ATOM
4305
CG1
ILE
593
27.403
58.244
62.148
1.00
18.67

1DLC
4429


ATOM
4306
CG2
ILE
593
28.219
59.189
59.962
1.00
20.92

1DLC
4430


ATOM
4307
CD1
ILE
593
26.812
56.980
61.577
1.00
17.37

1DLC
4431


ATOM
4308
N
ASN
594
25.512
61.331
62.456
1.00
27.20

1DLC
4432


ATOM
4309
CA
ASN
594
24.329
61.563
63.281
1.00
30.00

1DLC
4433


ATOM
4310
C
ASN
594
23.472
60.305
63.268
1.00
31.97

1DLC
4434


ATOM
4311
O
ASN
594
23.499
59.542
62.296
1.00
32.25

1DLC
4435


ATOM
4312
CB
ASN
594
23.495
62.698
62.712
1.00
33.50

1DLC
4436


ATOM
4313
CG
ASN
594
24.047
64.042
63.059
1.00
35.33

1DLC
4437


ATOM
4314
OD1
ASN
594
24.231
64.358
64.230
1.00
40.10

1DLC
4438


ATOM
4315
ND2
ASN
594
24.307
64.854
62.049
1.00
37.57

1DLC
4439


ATOM
4316
N
LYS
595
22.708
60.084
64.335
1.00
33.91

1DLC
4440


ATOM
4317
CA
LYS
595
21.833
58.913
64.390
1.00
35.24

1DLC
4441


ATOM
4318
C
LYS
595
20.936
58.918
63.159
1.00
33.13

1DLC
4442


ATOM
4319
O
LYS
595
20.454
59.970
62.740
1.00
31.59

1DLC
4443


ATOM
4320
CR
LYS
595
20.958
58.924
65.649
1.00
38.00

1DLC
4444


ATOM
4321
CG
LYS
595
21.607
58.302
66.882
1.00
45.73

1DLC
4445


ATOM
4322
CD
LYS
595
20.570
55.089
67.993
1.00
49.95

1DLC
4446


ATOM
4323
CE
LYS
595
20.323
59.344
68.835
1.00
53.81

1DLC
4447


ATOM
4324
NZ
LYS
595
21.391
59.568
69.861
1.00
54.01

1DLC
4448


ATOM
4325
N
GLY
596
20.803
57.763
62.525
1.00
34.32

1DLC
4449


ATOM
4326
CA
GLY
596
19.954
57.671
61.352
1.00
35.84

1DLC
4450


ATOM
4327
C
GLY
596
20.585
58.014
60.016
1.00
37.27

1DLC
4451


ATOM
4328
O
GLY
596
19.939
57.872
58.976
1.00
39.75

1DLC
4452


ATOM
4329
N
ASP
597
21.829
58.482
60.023
1.00
36.86

1DLC
4453


ATOM
4330
CA
ASP
597
22.502
58.810
58.772
1.00
33.14

1DLC
4454


ATOM
4331
C
ASP
597
22.864
57.551
58.002
1.00
30.98

1DLC
4455


ATOM
4332
O
ASP
597
23.057
56.487
58.589
1.00
30.44

1DLC
4456


ATOM
4333
CB
ASP
597
23.786
59.599
59.030
1.00
16.15

1DLC
4457


ATOM
4334
CG
ASP
597
23.530
61.040
59.404
1.00
38.83

1DLC
4458


ATOM
4335
OD1
ASP
597
22.359
61.481
59.389
1.00
43.82

1DLC
4459


ATOM
4336
OD2
ASP
597
24.516
61.739
59.707
1.00
41.04

1DLC
4460


ATOM
4337
N
THR
598
22.884
57.658
56.681
1.00
29.63

1DLC
4461


ATOM
4338
CA
THR
598
23.283
56.536
55.844
1.00
32.00

1DLC
4462


ATOM
4339
C
THR
598
24.793
56.650
55.683
1.00
28.95

1DLC
4463


ATOM
4340
O
THR
598
25.341
57.754
55.645
1.00
28.17

1DLC
4464


ATOM
4341
CB
THE
598
22.640
56.585
54.451
1.00
37.94

1DLC
4465


ATOM
4342
CG1
THR
598
22.909
57.857
53.839
1.00
44.78

1DLC
4466


ATOM
4343
CG2
THR
598
21.142
56.365
54.560
1.00
40.92

1DLC
4467


ATOM
4344
N
LEU
599
25.458
55.510
55.577
1.00
26.90

1DLC
4468


ATOM
4345
CA
LEU
599
26.908
55.483
55.446
1.00
24.58

1DLC
4469


ATOM
4346
C
LEU
599
27.4765
5.735
54.049
1.00
22.87

1DLC
4470


ATOM
4347
O
LEU
599
27.328
54.911
53.153
1.00
24.74

1DLC
4471


ATOM
4348
CB
LEU
599
27.449
54.166
56.003
1.00
22.58

1DLC
4472


ATOM
4349
CG
LEU
599
27.957
54.118
57.449
1.00
23.90

1DLC
4473


ATOM
4350
CD1
LEU
599
27.238
55.102
58.344
1.00
22.47

1DLC
4474


ATOM
4351
CD2
LET
599
27.829
52.693
57.973
1.00
23.37

1DLC
4475


ATOM
4352
N
THR
600
28.041
56.922
53.853
1.00
22.39

1DLC
4476


ATOM
4353
CA
THR
600
28.696
57.281
52.593
1.00
19.21

1DLC
4477


ATOM
4354
C
THR
600
30.187
57.440
52.899
1.00
19.66

1DLC
4478


ATOM
4355
O
THR
600
30.599
57.338
54.058
1.00
19.55

1DLC
4479


ATOM
4356
CB
THR
600
28.160
58.594
51.976
1.00
19.07

1DLC
4480


ATOM
4357
CG1
THR
600
28.297
59.671
52.911
1.00
19.57

1DLC
4481


ATOM
4358
CG2
THR
600
26.715
58.444
51.577
1.00
18.04

1DLC
4482


ATOM
4359
N
TYR
601
30.986
57.750
51.885
1.00
17.78

1DLC
4483


ATOM
4360
CA
TYR
601
32.426
57.884
52.072
1.00
17.44

1DLC
4484


ATOM
4361
C
TYR
601
32.891
58.710
53.278
1.00
18.41

1DLC
4485


ATOM
4362
O
TYR
601
33.715
58.256
54.064
1.00
18.54

1DLC
4486


ATOM
4363
CR
TYR
601
33.083
58.406
50.797
1.00
19.02

1DLC
4487


ATOM
4364
CG
TYR
601
34.576
58.213
50.799
1.00
20.72

1DLC
4488


ATOM
4365
CD1
TYR
601
35.132
56.947
50.612
1.00
23.42

1DLC
4489


ATOM
4366
CD2
TYR
601
35.435
59.281
51.036
1.00
20.19

1DLC
4490


ATOM
4367
CE1
TYR
601
36.509
56.747
50.665
1.00
23.81

1DLC
4491


ATOM
4368
CE2
TYR
601
36.809
59.098
51.094
1.00
18.57

1DLC
4492


ATOM
4369
CZ 
TYR
601
37.344
57.830
50.910
1.00
25.85

1DLC
4493


ATOM
4370
OH
TYR
601
38.712
57.644
50.988
1.00
30.21

1DLC
4494


ATOM
4371
N
ASN
602
32.336
59.905
53.440
1.00
21.65

1DLC
4495


ATOM
4372
CA
ASN
602
32.721
60.789
54.539
1.00
19.54

1DLC
4496


ATOM
4373
C
ASN
602
32.256
60.363
55.923
1.00
18.68

1DLC
4497


ATOM
4374
O
ASN
602
32.600
61.003
56.913
1.00
21.51

1DLC
4498


ATOM
4375
CB
ASN
602
32.248
62.219
54.262
1.00
22.37

1DLC
4499


ATOM
4376
CG
ASN
602
33.025
62.883
53.142
1.00
28.81

1DLC
4500


ATOM
4377
OD1
ASN
602
34.179
62.546
52.882
1.00
30.93

1DLC
4501


ATOM
4378
ND2
ASN
602
32.393
63.830
52.466
1.00
33.11

1DLC
4502


ATOM
4379
N
SER
603
31.458
59.305
55.995
1.00
18.60

1DLC
4503


ATOM
4380
CA
SER
603
30.956
58.828
57.280
1.00
18.99

1DLC
4504


ATOM
4381
C
SER
601
32.080
58.199
58.101
1.00
20.18

1DLC
4505


ATOM
4382
O
SER
603
32.060
58.219
59.334
1.00
20.27

1DLC
4506


ATOM
4383
CB
SER
603
29.859
57.775
57.094
1.00
21.15

1DLC
4507


ATOM
4384
OG
SER
603
28.932
58.158
56.099
1.00
22.65

1DLC
4508


ATOM
4385
N
PHE
604
33.043
57.611
57.400
1.00
18.74

1DLC
4509


ATOM
4386
CA
PHE
604
34.163
56.959
58.057
1.00
21.05

1DLC
4510


ATOM
4387
C
PHE
604
35.337
57.874
58.345
1.00
22.35

1DLC
4511


ATOM
4388
O
PHE
604
35.639
58.786
57.571
1.00
25.60

1DLC
4512


ATOM
4389
CB
PHE
604
34.642
55.761
57.243
1.00
17.33

1DLC
4513


ATOM
4390
CG
PHE
604
33.728
54.589
57.318
1.00
19.46

1DLC
4514


ATOM
4391
CD1
PHE
604
32.615
54.504
56.478
1.00
20.57

1DLC
4515


ATOM
4392
CD2
PHE
604
33.955
53.584
58.251
1.00
18.69

1DLC
4516


ATOM
4393
CE1
PHE
604
31.735
53.435
56.568
1.00
21.99

1DLC
4517


ATOM
4394
CE2
PHE
604
33.090
52.505
58.359
1.00
21.18

1DLC
4518


ATOM
4395
CZ
PHE
604
31.971
52.426
57.515
1.00
25.90

1DLC
4519


ATOM
4396
N
ASN
605
35.994
57.610
59.470
1.00
21.14

1DLC
4520


ATOM
4397
CA
ASN
605
37.168
56.359
59.890
1.00
19.17

1DLC
4521


ATOM
4398
C
ASN
605
38.294
57.351
60.132
1.00
17.19

1DLC
4522


ATOM
4399
U
ASN
605
38.033
56.195
60.457
1.00
13.48

1DLC
4523


ATOM
4400
CB
ASN
605
36.666
59.139
61.172
1.00
20.09

1DLC
4524


ATOM
4401
CG
ASN
605
38.083
59.882
61.715
1.00
24.94

1DLC
4525


ATOM
4402
OD1
ASN
605
38.877
60.446
60.961
1.00
23.59

1DLC
4526


ATOM
4403
ND2
ASN
605
38.230
59.886
63.029
1.00
23.22

1DLC
4527


ATOM
4404
N
LEU
606
39.529
57.768
59.862
1.00
15.78

1DLC
4528


ATOM
4405
CA
LEU
606
40.706
56.929
60.085
1.00
15.38

1DLC
4529


ATOM
4406
C
LEU
606
41.546
57.666
61.109
1.00
14.32

1DLC
4530


ATOM
4407
O
LEU
606
42.089
58.723
60.824
1.00
19.53

1DLC
4531


ATOM
4408
CB
LEU
606
41.512
56.726
58.803
1.00
11.43

1DLC
4532


ATOM
4409
CG
LEU
606
42.691
55.748
58.912
1.00
13.17

1DLC
4533


ATOM
4410
C71
LEU
606
42.188
54.310
59.013
1.00
8.03

1DLC
4534


ATOM
4411
CD2
LEU
606
43.591
55.891
57.712
1.00
11.28

1DLC
4535


ATOM
4412
N
ALA
607
41.610
57.132
62.316
1.00
14.53

1DLC
4536


ATOM
4413
CA
ALA
607
42.357
57.785
63.376
1.00
17.06

1DLC
4537


ATOM
4414
C
ALA
607
43.361
56.866
64.075
1.00
18.57

1DLC
4538


ATOM
4415
O
ALA
607
43.101
55.678
64.277
1.00
21.74

1DLC
4539


ATOM
4476
C
LEU
615
53.175
41.073
70.455
1.00
27.80

1DLC
4600


ATOM
4477
O
LEU
615
53.465
39.975
69.982
1.00
30.45

1DLC
4601


ATOM
4478
CB
LEU
615
52.558
41.746
68.128
1.00
24.01

1DLC
4602


ATOM
4479
CG
LEU
615
51.781
42.673
67.196
1.00
27.00

1DLC
4603


ATOM
4480
CD1
LEU 
615
51.591
41.995
65.850
1.00
26.98

1DLC
4604


ATOM
4481
CD2
LEU 
615
50.431
43.015
67.805
1.00
26.72

1DLC
4605


ATOM
4482
N
SER
616
53.162
41.311
71.759
1.00
28.53

1DLC
4606


ATOM
4483
CA
SER
616
53.525
40.292
72.744
1.00
34.72

1DLC
4607


ATOM
4484
C
SER
616
52.371
39.325
73.044
1.00
37.29

1DLC
4608


ATOM
4485
O
SER 
616
52.207
38.865
74.283
1.00
40.69

1DLC
4609


ATOM
4486
CS 
SER 
616
53.957
40.975
74.042
1.00
38.38

1DLC
4610


ATOM
4487
OG
SER 
616
52.908
41.795
74.545
1.00
40.32

1DLC
4611


ATOM
4488
N
GLY
617
51.575
39.027
72.021
1.00
35.36

1DLC
4612


ATOM
4489
CA
GLY
617
50.439
38.139
72.175
1.00
28.58

1DLC
4613


ATOM
4490
C
GLY 
617
49.746
37.935
70.846
1.00
27.52

1DLC
4614


ATOM
4491
O
GLY 
617
50.171
38.483
69.832
1.00
27.48

1DLC
4615


ATOM
4492
N
ASN 
618
48.673
37.152
70.836
1.00
26.58

1DLC
4616


ATOM
4493
CA
ASP 
618
47.958
36.898
69.588
1.00
25.03

1DLC
4617


ATOM
4494
C
ASN 
618
46.514
37.351
69.564
1.00
22.65

1DLC
4618


ATOM
4495
O
ASN 
618
45.993
37.679
68.513
1.00
24.08

1DLC
4619


ATOM
4496
CB
ASN
612
47.991
35.414
69.237
1.00
25.99

1DLC
4620


ATOM
9497
OG
ASN
618
49.388
34.872
69.126
1.00
27.81

1DLC
4621


ATOM
4498
OD1
ASN 
618
49.858
34.163
70.014
1.00
32.06

1DLC
4622


ATOM
4499
ND2
ASN 
618
50.060
35.191
68.038
1.00
28.41

1DLC
4623


ATOM
4500
N
ASN
619
45.857
37.337
70.711
1.00
21.28

1DLC
4624


ATOM
4501
CA
ASN
619
44.453
37.718
70.766
1.00
23.58

1DLC
4625


ATOM
4502
C
ASN 
619
44.187
39.189
70.986
1.00
23.07

1DLC
4626


ATOM
4503
O
ASN 
619
44.182
39.670
72.218
1.00
23.17

1DLC
4627


ATOM
4504
CS
ASN 
619
43.718
36.886
71.808
1.00
24.66

1DLC
4628


ATOM
4505
CG
ASN 
619
43.780
35.423
71.500
1.00
26.16

1DLC
4629


ATOM
4506
OD1
ASN 
619
42.964
34.912
70.754
1.00
30.61

1DLC
4630


ATOM
4507
ND2
ASN 
619
44.790
34.747
72.020
1.00
27.81

1DLC
4631


ATOM
4508
N
LEV 
620
43.962
39.897
69.888
1.00
24.96

1DLC
4632


ATOM
4509
CA
LEU 
620
43.681
41.320
69.938
1.00
24.70

1DLC
4633


ATOM
4510
C
LEG 
620
42.184
41.557
70.168
1.00
26.87

1DLC
4634


ATOM
4511
O
LEG 
620
41.332
41.071
69.421
1.00
26.49

1DLC
4635


ATOM
4512
CB
LEU 
620
44.132
41.996
68.640
1.00
21.52

1DLC
4636


ATOM
4513
CG
LEU 
620
43.980
43.521
68.582
1.00
21.06

1DLC
4617


ATOM
4514
CD1
LEU 
620
44.827
44.159
69.665
1.00
22.05

1DLC
4638


ATOM
4515
CD2
LEU 
620
44.383
44.042
67.220
1.00
19.94

1DLC
4639


ATOM
4516
N
GLN 
621
41.871
42.295
71.222
1.00
26.81

1DLC
4640


ATOM
4517
CA
GLN 
621
40.490
42.606
71.533
1.00
28.41

1DLC
4641


ATOM
4518
C
GLN 
621
40.238
44.107
71.450
1.00
27.09

1DLC
4642


ATOM
4519
O
GLN 
621
41.003
44.909
71.987
1.00
26.35

1DLC
4643


ATOM
4520
CB
GLN 
621
40.127
42.097
72.926
1.00
30.85

1DLC
4644


ATOM
4521
CG
GLN 
621
38.687
42.369
73.303
1.00
38.10

1DLC
4645


ATOM
4522
CD
GLN 
621
38.395
42.019
74.741
1.00
42.94

1DLC
4646


ATOM
4523
OE1
GLN 
621
38.025
40.885
75.054
1.00
46.82

1DLC
4647


ATOM
4524
NE2
GLN 
621
38.573
42.984
75.635
1.00
43.76

1DLC
4648


ATOM
4525
N
ILE 
522
39.193
44.480
70.723
1.00
27.04

1DLC
4649


ATOM
4526
CA
ILE 
622
38.819
45.881
70.585
1.00
24.51

1DLC
4650


ATOM
4527
C
ILE 
622
37.571
46.089
71.440
1.00
23.99

1DLC
4651


ATOM
4528
O
ILE 
622
36.602
45.342
71.329
1.00
24.51

1DLC
4652


ATOM
4529
CB
ILE 
622
38.491
46.269
69.113
1.00
25.00

1DLC
4653


ATOM
4530
CG1
ILE 
622
39.637
45.890
68.169
1.00
25.97

1DLC
4654


ATOM
4531
CG2
ILE 
622
38.266
47.772
69.005
1.00
22.97

1DLC
4655


ATOM
4532
CD1
ILE 
622
39.668
44.433
57.761
1.00
32.60

1DLC
4656


ATOM
4533
N
GLY
623
37.615
47.075
72.323
1.00
24.24

1DLC
4657


ATOM
4534
CA
GLY
623
36.476
47.360
73.178
1.00
23.29

1DLC
4658


ATOM
4535
C
GLY 
623
36.019
48.798
72.985
1.00
27.25

1DLC
4659


ATOM
4536
O
GLY
623
36.825
49.682
72.673
1.00
28.11

1DLC
4660


ATOM
4537
N
VAL
624
34.731
49.048
73.184
1.00
26.21

1DLC
4661


ATOM
4538
CA
VAL
624
34.197
50.390
73.009
1.00
24.65

1DLC
4662


ATOM
4539
C
VAL
624
33.390
50.847
74.217
1.00
25.91

1DLC
4663


ATOM
4540
O
VAL
624
32.695
50.060
74.854
1.00
28.03

1DLC
4664


ATOM
4541
CB
VAL
624
33.252
50.470
71.780
1.00
22.56

1DLC
4665


ATOM
4542
CG1
VAL
624
33.075
51.903
71.367
1.00
21.19

1DLC
4666


ATOM
4543
CG2
VAL
624
33.774
49.633
70.624
1.00
24.76

1DLC
4667


ATOM
4544
N
THR
625
33.528
52.117
74.564
1.00
25.09

1DLC
4668


ATOM
4545
CA
THE
625
32.755
52.693
75.653
1.00
24.39

1DLC
4669


ATOM
4546
C
THE
525
32.428
54.119
75.281
1.00
24.42

1DLC
4670


ATOM
4547
O
THR
625
33.051
54.700
74.387
1.00
22.03

1DLC
4671


ATOM
4548
CB
THR
625
33.473
52.690
77.007
1.00
24.18

1DLC
4672


ATOM
4549
OG1
THE
625
34.753
53.312
76.877
1.00
30.48

1DLC
4673


ATOM
4550
CG2
THR
625
33.610
51.271
77.544
1.00
25.23

1DLC
4674


ATOM
4551
N
GLY
626
31.432
54.672
75.956
1.00
28.18

1DLC
4675


ATOM
4552
CA
GLY
626
31.015
56.034
75.672
1.00
29.72

1DLC
4676


ATOM
4553
C
GLY
626
29.721
56.089
74.881
1.00
30.01

1DLC
4677


ATOM
4554
O
GLY
626
29.311
57.162
74.438
1.00
34.83

1DLC
4678


ATOM
4555
N
LEO
627
29.102
54.931
74.668
1.00
27.34

1DLC
4679


ATOM
4556
CA
LEO
627
27.840
54.852
73.946
1.00
28.54

1DLC
4680


ATOM
4557
C
LEU
627
26.655
55.102
74.872
1.00
31.09

1DLC
4681


ATOM
4558
O
LEO
627
26.687
54.772
76.058
1.00
32.97

1DLC
4682


ATOM
4559
CB
LEO
627
27.668
53.483
73.288
1.00
25.31

1DLC
4683


ATOM
4560
CG
LEU
627
28.673
53.087
72.211
1.00
24.90

1DLC
4684


ATOM
4561
CD1
LEU
627
28.212
51.813
71.544
1.00
25.05

1DLC
4685


ATOM
4562
CD2
LEU
627
28.784
54.196
71.185
1.00
26.40

1DLC
4686


ATOM
4563
N
SER
628
26.619
55.711
74.316
1.00
33.11

1DLC
4687


ATOM
4564
CA
SER
628
24.390
56.000
75.038
1.00
32.54

1DLC
4688


ATOM
4565
C
SER
628
23.306
55.280
74.259
1.00
34.13

1DLC
4689


ATOM
4566
O
SER
628
23.539
54.854
73.126
1.00
34.40

1DLC
4690


ATOM
4567
CS
SER
628
24.108
57.500
75.031
1.00
34.45

1DLC
4691


ATOM
4568
OG
SER
628
25.205
58.224
75.563
1.00
43.41

1DLC
4692


ATOM
4569
N
ALA
629
22.121
55.141
74.842
1.00
36.19

1DLC
4693


ATOM
4570
CA
ALA
629
21.026
54.462
74.149
1.00
35.18

1DLC
4694


ATOM
4571
C
ALA
629
20.802
55.085
72.769
1.00
32.86

1DLC
4695


ATOM
4572
O
ALA
629
20.722
56.307
72.632
1.00
33.61

1DLC
4696


ATOM
4573
CB
ALA
629
19.753
54.536
74.977
1.00
38.53 .

1DLC
4697


ATOM
4574
N
GLY
630
20.776
54.250
71.739
1.00
31.19

1DLC
4598


ATOM
4575
CA
GLY
630
20.572
54.767
70.397
1.00
31.13

1DLC
4699


ATOM
4576
C
GLY
630
21.845
55.068
69.625
1.00
30.12

1DLC
4700


ATOM
4577
O
GLY
630
21.797
55.416
68.440
1.00
29.53

1DLC
4701


ATOM
4578
N
ASP
631
22.984
54.975
70.303
1.00
29.51

1DLC
4702


ATOM
4579
CA
ASP
631
24.269
55.204
69.658
1.00
29.05

1DLC
4703


ATOM
4580
C
ASP
631
24.772
53.950
68.958
1.00
26.70

1DLC
4704


ATOM
4581
O
ASP
631
24.535
52.834
69.409
1.00
25.70

1DLC
4705


ATOM
4582
CB
ASP
631
25.315
55.686
70.662
1.00
30.55

1DLC
4706


ATOM
4583
CG
ASP
631
25.248
57.175
70.902
1.00
29.06

1DLC
4707


ATOM
4584
001
ASP
631
24.974
57.917
69.940
1.00
32.20

1DLC
4708


ATOM
4585
002
ASP
631
25.480
57.608
72.050
1.00
32.19

1DLC
4709


ATOM
4586
N
LYS
632
25.448
54.155
67.836
1.00
27.29

1DLC
4710


ATOM
4587
CA
LYS
632
26.001
53.063
67.041
1.00
28.14

1DLC
4711


ATOM
4588
C
LYS
632
27.423
53.376
66.582
1.00
28.21

1DLC
4712


ATOM
4589
O
LYS
632
27.751
54.529
66.259
1.00
27.32

1DLC
4713


ATOM
4590
CB
LYS
632
25.144
52.822
65.796
1.00
30.56

1DLC
4714


ATOM
4591
CG
LYS
632
24.302
51.570
65.808
1.00
34.27

1DLC
4715


ATOM
4592
CD
LYS
632
22.833
51.929
65.849
1.00
38.40

1DLC
4716


ATOM
4593
CE
LYS
632
21.989
50.859
65.198
1.00
38.52

1DLC
4717


ATOM
4594
NZ
LYS
632
22.334
50.732
63.756
1.00
39.82

1DLC
4718


ATOM
4595
N
VAL
633
28.257
52.337
66.557
1.00
27.38

1DLC
4719


ATOM
4596
CA
VAL
633
29.644
52.437
66.097
1.00
21.96

1DLC
4720


ATOM
4597
C
VAL
633
29.876
51.322
65.082
1.00
20.64

1DLC
4721


ATOM
4598
O
VAL
633
29.526
50.173
65.324
1.00
16.03

1DLC
4722


ATOM
4599
CR
VAL
633
30.665
52.281
67.244
1.00
20.74

1DLC
4723


ATOM
4600
CG1
VAL
633
32.082
52.171
66.701
1.00
21.42

1DLC
4724


ATOM
4601
CG2
VAL
633
30.462
53.360
68.275
1.00
21.81

1DLC
4725


ATOM
4602
N
TYR
634
30.393
51.687
63.917
1.00
21.62

1DLC
4726


ATOM
4603
CA
TYR
634
30.687
50.729
62.859
1.00
19.61

1DLC
4727


ATOM
4604
C
TYR
634
32.199
50.649
62.704
1.00
20.81

1DLC
4728


ATOM
4605
O
TYR
634
32.872
51.675
62.583
1.00
19.65

1DLC
4729


ATOM
4606
CB
TYR
634
30.072
51.188
61.541
1.00
20.60

1DLC
4730


ATOM
4607
CG
TYR
634
28.582
51.418
61.612
1.00
24.53

1DLC
4731


ATOM
4608
CD1
TYR
634
28.069
52.660
61.978
1.00
22.76

1DLC
4732


ATOM
4609
CD2
TYR
634
27.684
50.392
61.306
1.00
24.10

1DLC
4733


ATOM
4610
CE1
TYR
634
26.713
52.877
62.036
1.00
26.60

1DLC
4734


ATOM
4611
CE2
TYR
634
26.321
50.598
61.359
1.00
24.93

1DLC
4735


ATOM
4612
CZ
TYR
634
25.839
51.845
61.723
1.00
29.72

1DLC
4736


ATOM
4613
OH
TYR
634
24.481
52.074
61.754
1.00
34.36

1DLC
4737


ATOM
4614
N
ILE
635
32.741
49.438
62.750
1.00
20.73

1DLC
4738


ATOM
4615
CA
ILE
635
34.182
49.257
62.602
1.00
18.75

1DLC
4739


ATOM
4616
C
ILE
635
34.474
48.479
61.340
1.00
16.63

1DLC
4740


ATOM
4617
O
ILE
635
33.941
47.398
61.115
1.00
17.24

1DLC
4741


ATOM
4618
CB
ILE
635
34.811
48.520
63.794
1.00
20.45

1DLC
4742


ATOM
4619
CG1
ILE
635
34.344
49.147
65.119
1.00
22.26

1DLC
4743


ATOM
4620
CG2
ILE
635
36.329
48.591
63.692
1.00
22.68

1DLC
4744


ATOM
4621
CD1
ILE
635
34.684
48.321
66.359
1.00
21.31

1DLC
4745


ATOM
4622
N
ASP
636
35.302
49.070
60.499
1.00
17.78

1DLC
4746


ATOM
4623
CA
ASP
636
35.683
48.464
59.241
1.00
17.49

1DLC
4747


ATOM
4624
C
ASP
636
36.993
47.673
59.370
1.00
18.04

1DLC
4748


ATOM
4625
O
ASP
636
37.003
46.440
59.251
1.00
17.98

1DLC
4749


ATOM
4626
CB
ASP
636
35.802
49.561
58.170
1.00
15.99

1DLC
4750


ATOM
4627
CO
ASP
636
36.303
49.036
56.842
1.00
18.79

1DLC
4751


ATOM
4628
OD1
ASP
636
35.896
47.926
56.440
1.00
25.68

1DLC
4752


ATOM
4629
OD2
ASP
636
37.109
49.733
56.197
1.00
18.48

1DLC
4753


ATOM
4630
N
LYS
637
38.083
48.381
59.670
1.00
18.05

1DLC
4754


ATOM
4631
CA
LYS
637
39.402
47.758
59.775
1.00
16.49

1DLC
4755


ATOM
4632
C
LYS
637
40.305
48.342
60.846
1.00
15.84

1DLC
4756


ATOM
4633
O
LYS
637
40.099
49.462
61.305
1.00
19.42

1DLC
4757


ATOM
4634
CB
LYS
637
40.153
47.887
58.441
1.00
13.95

1DLC
4758


ATOM
4635
CG
LYS
637
39.432
47.343
57.217
1.00
15.81

1DLC
4759


ATOM
4636
CD
LYS
637
40.290
47.503
55.987
1.00
15.16

1DLC
4760


ATOM
4637
CE
LYS
637
39.562
47.083
54.729
1.00
18.94

1DLC
4761


ATOM
4638
NZ
LYS
637
38.566
48.094
54.290
1.00
25.98

1DLC
4762


ATOM
4639
N
ILE
638
41.285
47.547
61.255
1.00
17.01

1DLC
4763


ATOM
4640
CA
ILE
638
42.312
47.967
62.205
1.00
18.44

1DLC
4764


ATOM
4641
C
ILE
638
43.590
47.876
61.359
1.00
18.91

1DLC
4765


ATOM
4642
O
ILE
638
43.728
46.979
60.528
1.00
17.29

1DLC
4766


ATOM
4643
CB
ILE
638
42.402
47.038
63.455
1.00
19.92

1DLC
4767


ATOM
4644
CG1
ILE
638
43.633
47.371
64.303
1.00
23.39

1DLC
4768


ATOM
4645
CO2
ILE
638
42.467
45.589
63.051
1.00
22.91

1DLC
4769


ATOM
4646
CD1
ILE
638
43.463
48.546
65.222
1.00
25.42

1DLC
4770


ATOM
4647
N
GLU
639
44.452
48.876
61.467
1.00
19.60

1DLC
4771


ATOM
4648
CA
GLU
639
45.693
48.893
60.699
1.00
19.14

1DLC
4772


ATOM
4649
C
GLU
639
46.903
48.901
61.614
1.00
19.79

1DLC
4773


ATOM
4650
O
GLU
639
46.878
49.481
62.704
1.00
20.61

1DLC
4774


ATOM
4651
CE
GLU
639
45.772
50.131
59.807
1.00
21.25

1DLC
4775


ATOM
4652
CG
GLU
639
44.596
50.362
58.880
1.00
20.87

1DLC
4776


ATOM
4653
CD
GLU
639
44.831
51.536
57.938
1.00
21.31

1DLC
4777


ATOM
4654
OE1
GLU
639
45.626
52.437
58.270
1.00
23.01

1DLC
4778


ATOM
4655
OE2
GLU
639
44.225
51.560
56.853
1.00
23.98

1DLC
4779


ATOM
4656
N
PHE
640
47.969
48.259
61.162
1.00
18.90

1DLC
4790


ATOM
4657
CA
PHE
640
49.193
48.212
61.940
1.00
18.35

1DLC
4781


ATOM
4658
C
PHE
640
50.310
48.862
61.154
1.00
18.44

1DLC
4782


ATOM
4659
O
PHE
640
50.542
48.535
59.986
1.00
19.24

1DLC
4783


ATOM
4660
CR
PHE
640
49.552
46.775
62.303
1.00
18.10

1DLC
4784


ATOM
4661
CG
PHE
640
48.503
46.086
63.121
1.00
19.75

1DLC
4785


ATOM
4662
CD1
PHE
640
47.457
45.408
62.504
1.00
22.39

1DLC
4786


ATOM
4663
CD2
PHE
640
48.548
46.122
64.508
1.00
21.02

1DLC
4787


ATOM
4664
CE1
RHE
640
46.471
44.774
63.260
1.00
23.22

1DLC
4788


ATOM
4665
CE2
PHE
640
47.562
45.488
65.275
1.00
20.83

1DLC
4789


ATOM
4666
CZ
PHE
640
46.528
44.816
64.649
1.00
21.24

1DLC
4790


ATOM
4657
N
ILE
641
50.935
49.855
61.773
1.00
18.54

1DLC
4791


ATOM
4658
CA
ILE
641
52.032
50.574
61.148
1.00
17.65

1DLC
4792


ATOM
4669
C
ILE
641
53.354
50.254
61.525
1.00
18.10

1DLC
4793


ATOM
4670
O
TLE
641
53.532
50.515
63.020
1.00
16.34

1DLC
4794


ATOM
4671
CB
ILE
641
51.806
52.098
61.187
1.00
19.28

1DLC
4795


ATOM
4672
CG1
ILE
641
50.490
52.443
60.484
1.00
16.97

1DLC
4796


ATOM
4673
CG2
ILE
641
52.994
52.823
60.536
1.00
16.12

1DLC
4791


ATOM
4674
CD1
ILE
641
50.125
53.890
60.562
1.00
20.58

1DLC
4798


ATOM
4675
N
PRO
642
54.270
49.611
61.084
1.00
21.02

1DLC
4799


ATOM
4676
CA
PRO
642
55.590
49.252
61.616
1.00
22.98

1DLC
4800


ATOM
4677
C
PRO
642
56.315
50.542
61.966
1.00
24.81

1DLC
4801


ATOM
4678
O
PRO
642
56.451
51.442
61.131
1.00
29.36

1DLC
4802


ATOM
4679
CR
PRO
642
56.237
48.499
60.451
1.00
20.26

1DLC
4803


ATOM
4680
CG
PRO
642
55.532
49.048
59.237
1.00
23.90

1DLC
4804


ATOM
4681
CD
PRO
642
54.113
49.142
59.697
1.00
21.85

1DLC
4805


ATOM
4682
N
VAL
643
56.741
50.647
63.216
1.00
27.45

1DLC
4806


ATOM
4683
CA
VAL
643
57.389
51.859
63.694
1.00
31.83

1DLC
4807


ATOM
4684
C
VAL
643
58.701
51.581
64.435
1.00
36.92

1DLC
4808


ATOM
4685
O
VAL
643
58.839
50.545
65.083
1.00
41.24

1DLC
4809


ATOM
4686
CB
VAL
643
56.372
52.642
64.579
1.00
29.35

1DLC
4810


ATOM
4687
CG1
VAL
643
56.972
53.075
65.901
1.00
25.64

1DLC
4811


ATOM
4688
CG2
VAL
643
55.810
53.807
63.806
1.00
21.99

1DLC
4812


ATOM
4689
N
ASN
644
59.668
52.487
64.301
1.00
41.01

1DLC
4813


ATOM
4690
CA
ASN
644
60.962
52.336
64.973
1.00
46.63

1DLC
4814


ATOM
4691
C
ASN
644
60.972
52.790
66.436
1.00
49.51

1DLC
4815


ATOM
4692
O
ASN
G44
60.080
53.575
66.835
1.00
52.85

1DLC
4816


ATOM
4693
CB
ASN
644
62.067
53.061
64.204
1.00
45.33

1DLC
4817


ATOM
4694
CO
ASN
644
62.467
52.332
62.940
1.00
48.91

1DLC
4818


ATOM
4695
001
ASN
644
62.868
52.952
61.955
1.00
51.43

1DLC
4819


ATOM
4696
ND2
ASN
644
62.365
51.008
62.957
1.00
48.98

1DLC
4820


ATOM
4697
OXT 
ASN
644
61.887
52.354
67.174
1.00
54.29

1DLC
4821


TER
4698

ASN
644






1DLC
4822


HETATM 
4699
O
HOH
1
28.158
55.658
35.558
1.00
15.93

1DLC
4823


HETATM 
4700
O
HOH
2
30.007
42.529
51.310
1.00
29.97

1DLC
4824


HETATM 
4701
O
HOH
3
36.424
37.532
49.700
1.00
18.65

1DLC
4825


HETATM 
4702
O
HOH
4
37.001
54.392
48.062
1.00
10.97

1DLC
4826


HETATM 
4703
O
HOH
5
41.124
51.393
35.747
1.00
18.84

1DLC
4827


HETATM 
4704
O
HOH
6
39.377
60.985
65.970
1.00
19.48

1DLC
4828


HETATM 
4705
O
HOH
7
26.260
28.918
41.587
1.00
14.99

1DLC
4829


HETATM 
4706
O
HOH
8
33.639
33.867
54.596
1.00
15.88

1DLC
4830


HETATM 
4707
O
HOH
9
51.981
45.967
59.702
1.00
20.77

1DLC
4831


HETATM 
4708
O
HOH
10
49.865
76.628
42.176
1.00
46.98

1DLC
4832


HETATM 
4709
O
HOH
11
56.250
42.866
68.444
1.00
32.76

1DLC
4833


HETATM 
4710
O
HOH
12
48.128
58.353
60.425
1.00
13.12

1DLC
4834


HETATM 
4711
O
HOH
13
39.909
31.847
39.167
1.00
22.65

1DLC
4835


HETATM 
4712
O
HUH
14
42.525
40.309
74.464
1.00
21.75

1DLC
4836


HETATM 
4713
O
HOH
15
35.320
44.237
58.596
1.00
20.02

1DLC
4837


HETATM 
4714
O
HOH
16
42.939
52.321
46.818
1.00
20.43

1DLC
4838


HETATM 
4715
O
HOH
17
34.791
45.871
55.097
1.00
17.61

1DLC
4839


HETATM
4716
O
HOH
18
59.791
70.818
25.850
1.00
58.06

1DLC
4840


HETATM
4717
0
HOH
19
49.421
53.503
45.093
1.00
28.93

1DLC
4841


HETATM
4718
O
HOH
20
26.124
35.366
50.587
1.00
20.75

1DLC
4842


HETATM
4719
O
HOH
21
22.215
55.259
63.293
1.00
55.44

1DLC
4843


HETATM
4720
O
HOH
22
29.336
36.466
34.470
1.00
28.07

1DLC
4844


HETATM
4721
O
HOH
23
36.856
28.547
51.651
1.00
25.28

1DLC
4845


HETATM
4722
O
HOH
24
32.887
40.556
54.227
1.00
18.71

1DLC
4846


HETATM
4723
O
HOH
25
11.473
29.145
36.339
1.00
30.31

1DLC
4847


HETATM
4724
O
HOH
26
29.975
51.053
31.090
1.00
24.69

1DLC
4848


HETATM
4725
O
HOH
27
23.211
34.799
38.939
1.00
18.55

1DLC
4849


HETATM
4726
O
HOH
28
40.839
35.808
64.000
1.00
20.47

1DLC
4850


HETATM
4727
O
HOH
29
48.014
63.906
44.198
1.00
20.94

1DLC
4851


HETATM
4728
O
HOH
30
38.825
30.321
41.019
1.00
17.31

1DLC
4852


HETATM
4729
O
HOH
31
43.802
60.051
66.555
1.00
21.11

1DLC
4853


HETATM
4730
O
HUH
32
38.144
26.579
49.130
1.00
19.35

1DLC
4854


HETATM
4731
O
HOH
33
38.268
41.944
41.244
1.00
29.87

1DLC
4855


HETATM
4732
O
HOH
34
37.512
21.444
38.474
1.00
24.99

1DLC
4856


HETATM
4733
O
HOH
35
32.702
36.732
53.626
1.00
20.86

1DLC
4857


HETATM
4734
O
HOH
36
49.899
63.801
28.431
1.00
28.04

1DLC
4858


HETATM
4735
O
HOH
37
49.371
53.132
68.181
1.00
26.75

1DLC
4859


HETATM
4736
O
HOH
38
29.606
38.319
55.430
1.00
25.89

1DLC
4860


HETATM
4737
O
HOH
39
41.950
72.970
42.722
1.00
27.25

1DLC
4861


HETATM
4738
O
HOH
40
39.554
70.091
45.032
1.00
44.51

1DLC
4862


HETATM
4739
O
HOH
41
43.093
57.590
52.155
1.00
22.06

1DLC
4863


HETATM
4740
O
HOH
42
36.402
31.325
52.356
1.00
14.91

1DLC
4864


HETATM
4741
O
HOH
43
42.564
71.403
44.910
1.00
26.89

1DLC
4865


HETATM
4742
O
HOH
44
31.202
36.895
36.508
1.00
20.87

1DLC
4866


HETATM
4743
O
HOH
45
9.974
36.335
44.772
1.00
23.38

1DLC
4867


HETATM
4744
O
HOH
46
17.109
18.398
39.762
1.00
24.03

1DLC
4868


HETATM
4745
O
HOH
47
26.895
37.648
43.823
1.00
21.28

1DLC
4869


HETATM
4746
O
HOH
48
19.711
22.004
38.604
1.00
24.53

1DLC
4870


HETATM
4747
O
HOH
49
37.262
44.313
53.204
1.00
43.74

1DLC
4871


HETATM
4748
O
HOH
50
33.936
47.399
47.859
1.00
22.31

1DLC
4872


HETATM
4749
O
HOH
51
30.403
46.461
72.142
1.00
32.70

1DLC
4873


HETATM
4750
O
HOW
52
46.001
19.419
46.812
1.00
40.72

1DLC
4874


HETATM
4751
O
HOH
53
45.816
40.175
53.356
1.00
25.45

1DLC
4875


HETATM
4752
O
HOH
54
30.264
60.779
51.534
1.00
25.95

1DLC
4876


HETATM
4753
O
HOH
55
10.154
28.983
45.205
1.00
22.19

1DLC
4877


HETATM
4754
O
HOH
56
28.704
26.404
57.946
1.00
26.44

1DLC
4878


HETATM
4755
O
HOH
57
32.699
38.030
55.930
1.00
23.26

1DLC
4879


HETATM
4756
O
HOH
58
14.955
11.719
28.113
1.00
48.40

1DLC
4880


HETATM
4757
O
HOH
59
18.793
41.375
48.389
1.00
46.53

1DLC
4881


HETATM
4758
O
HOH
60
36.654
53.190
50.493
1.00
27.58

1DLC
4862


HETATM
4759
O
HOH
61
41.276
73.788
36.658
1.00
32.95

1DLC
4883


HETATM
4760
O
HOH
62
47.841
44.305
49.214
1.00
32.69

1DLC
4854


HETATM
4761
O
HOH
63
35.489
33.715
61.967
1.00
28.50

1DLC
4885


HETATM
4762
O
HOH
64
56.538
77.886
37.982
1.00
50.68

1DLC
4886


HETATM
4763
O
HOH
65
18.717
10.880
30.116
1.00
45.47

1DLC
4887


HETATM
4764
O
HOH
66
36.692
51.483
75.590
1.00
36.31

1DLC
4888


HETATM
4765
O
HOH
67
20.585
18.690
41.004
1.00
34.39

1DLC
4889


HETATM
4766
O
HOH
68
40.508
40.198
41.474
1.00
39.41

1DLC
4890


HETATM
4767
O
HOH
69
39.908
45.560
74.947
1.00
33.34

1DLC
4891


HETATM
4768
O
HOH
70
14.617
25.579
48.494
1.00
25.51

1DLC
4892


HETATM
4769
O
HOH
71
46.860
64.590
54.372
1.00
34.61

1DLC
4893


HETATM
4770
O
HOH
72
38.042
46.135
38.081
1.00
30.46

1DLC
4894


HETATM
4771
O
HOH
73
14.223
18.604
37.526
1.00
33.61

1DLC
4895


HETATM
4772
O
HOH
74
41.396
33.509
59.099
1.00
33.96

1DLC
4896


HETATM
4773
O
HOH
75
36.159
56.059
54.037
1.00
29.86

1DLC
4897


HETATM
4774
O
HOH
76
25.313
32.849
50.116
1.00
32.15

1DLC
4898


HETATM
4775
O
HOH
77
11.778
10.641
30.101
1.00
44.03

1DLC
4899


HETATM
4776
O
HOH
78
42.893
28.299
64.966
1.00
47.47

1DLC
4900


HETATM
4777
O
HOH
79
46.675
54.242
75.812
1.00
38.86

1DLC
4901


HETATM
4778
O
HOH
80
45.755
41.679
55.898
1.00
34.63

1DLC
4902


HETATM
4779
O
HOH
81
25.484
44.446
46.854
1.00
35.35

1DLC
4903


HETATM
4780
O
HOH
82
15.402
8.669
44.437
1.00
51.05

1DLC
4904


HETATM
4781
O
HOH
83
29.189
60.967
26.317
1.00
41.92

1DLC
4905


HETATM
4782
O
HOH
84
28.869
40.731
48.778
1.00
51.15

1DLC
4906


HETATM
4783
O
HOH
85
45.082
38.563
44.823
1.00
33.55

1DLC
4907


HETATM
4784
O
HOH
86
1.705
23.575
29.683
1.00
48.74

1DLC
4908


HETATM
4785
O
HOH
87
27.621
39.569
70.673
1.00
40.98

1DLC
4909


HETATM
4786
O
HOH
88
26.000
29.161
48.418
1.00
29.63

1DLC
4910


HETATM
4787
O
HOH
89
25.317
11.429
47.522
1.00
27.37

1DLC
4911


HETATM
4788
O
HOH
90
30.222
33.188
52.083
1.00
37.13

1DLC
4912


HETATM
4789
O
HOH
91
38.198
20.113
36.178
1.00
61.28

1DLC
4913


HETATM
4790
O
HOH
92
36.499
29.557
39.290
1.00
29.56

1DLC
4914


HETATM
4791
O
HOH
93
19.705
36.665
52.735
1.00
35.61

1DLC
4915


HETATM
4792
O
HOH
94
26.086
41.897
52.19
1.00
48.74

1DLC
4916


HETATM
4793
O
HOH
95
44.038
20.253
40.363
1.00
39.20

1DLC
4917


HETATM
4794
O
HOH
96
31.519
47.240
51.443
1.00
28.48

1DLC
4918


HETATM
4795
O
HOH
97
29.028
35.445
61.838
1.00
35.57

1DLC
4919


HETATM
4796
O
HOH
98
14.327
29.302
33.611
1.00
41.11

1DLC
4920


HETATM
4797
O
HOH
99
19.576
61.182
35.587
1.00
45.66

1DLC
4921


HETATM
4798
O
HUH
100
56.227
72.862
32.221
1.00
54.49

1DLC
4922


HETATM
4799
O
HOH
101
15.572
41.260
35.469
1.00
34.12

1DLC
4923


HETATM
4800
O
HOH
102
46.292
25.845
33.724
1.00
52.88

1DLC
4924


HETATM
4801
O
HOH
103
32.306
63.512
40.031
1.00
53.52

1DLC
4925


HETATM
4802
O
HUH
104
34.104
44.558
47.227
1.00
32.41

1DLC
4926


HETATM
4803
O
HOH
105
44.964
39.206
57.270
1.00
43.16

1DLC
4927


HETATM
4804
O
HOH
106
56.545
54.651
60.410
1.00
56.15

1DLC
4928











MASTER
63
  2   0   0   0   0   0    6  4803 1  0  45
1DLC
4929









END
1DLC
4930

## Claims

1. A transgenic plant comprising a gene encoding a modified Cry3Bb* polypeptide, wherein said modified Cry3Bb* polypeptide comprises one or more amino acids within loop α7, β1replaced with one or more amino acids resulting increased flexibility of the loop, wherein said replacement results in one or more amino acid substitutions selected from the group consisting of Tyr287 replaced by phenylalanine, Asp288 replaced by asparagines, Ile289 replaced by threonine or valine, Arg290 replaced by valine, asparagines or leucine, Leu291 replaced by arginine, Tyr292 replaced by phenylalanine, and Ser293 replaced by arginine or proline.

2. The transgenic plant of claim 1, wherein said gene encodes a modified Cry3Bb* polypeptide selected from the group consisting of SEQ ID NO:14, SEQ ID NO:28, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:62 and SEQ ID NO:64.

3. The transgenic plant of claim 2, wherein said gene comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:61 and SEQ ID NO:63.

4. A progeny plant or seed from the transgenic plant of any one of claims 1 to 3, wherein said progeny plant or seed comprises said gene encoding said modified Cry3Bb* polypeptide.

5. Seed from the progeny plant of claim 4, wherein said seed comprises said gene encoding said modified Cry3Bb* polypeptide.

6. A plant from the seed of claim 5, wherein said plant comprises said gene encoding said modified Cry3Bb* polypeptide.

7. A method of preparing a Coleopteran-resistant transgenic plant, said method comprising the steps of:
(a) obtaining a nucleic acid segment comprising a gene encoding a modified Cry3Bb* polypeptide, wherein said modified Cry3Bb* polypeptide comprises one or more amino acids within loop α7, β1 replaced with one or more amino acids resulting increased flexibility of the loop, wherein said replacement results in one or more amino acid substitutions selected from the group consisting of Tyr287 replaced by phenylalanine, Asp288 replaced by asparagines, Ile289 replaced by threonine or valine, Arg290 replaced by valine, asparagines or leucine, Leu291 replaced by arginine, Tyr292 replaced by phenylalanine, and Ser293 replaced by arginine or proline;
(b) transforming a plant cell with said nucleic acid segment; and
(c) regenerating from said plant cell a transgenic plant, which expresses said modified Cry3Bb* polypeptide and wherein said transgenic plant is resistant to Coleopteran insects as compared to a non-transformed plant.

8. The method of claim 7, wherein step a) further comprises introducing said nucleic acid segment into a vector, and wherein step b) comprises transforming said plant cell with said vector.

9. The method of claim 8, wherein said vector is a phage vector, bacterial vector or viral vector.

10. The method of any one of claims 7 to 9, wherein said gene encodes a modified Cry3Bb* polypeptide selected from the group consisting of SEQ ID NO:14, SEQ ID NO:28, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:62 and SEQ ID NO:64.

11. The method of claim 10, wherein said gene comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:61 and SEQ ID NO:63.

12. A method of preparing Coleopteran-resistant plant seed, said method comprising the steps of:
(a) transforming a plant cell with a nucleic acid segment comprising a gene encoding a modified Cry3Bb* polypeptide, wherein said modified Cry3Bb* polypeptide comprises one or more amino acids within loop α7, β1 replaced with one or more amino acids resulting increased flexibility of the loop, wherein said replacement results in one or more amino acid substitutions selected from the group consisting of Tyr287 replaced by phenylalanine, Asp288 replaced by asparagines, Ile289 replaced by threonine or valine, Arg290 replaced by valine, asparagines or leucine, Leu291 replaced by arginine, Tyr292 replaced by phenylalanine, and Ser293 replaced by arginine or proline;
(b) producing a transgenic plant from said transformed plant cell; and
(c) obtaining seed from said transgenic plant, wherein said seed exhibits increased Coleopteran-resistance as compared to non-transformed seed.

13. The method of claim 12, wherein said gene encodes a modified Cry3Bb* polypeptide selected from the group consisting of SEQ ID NO:14, SEQ ID NO:28, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:62 and SEQ ID NO:64.

14. The method of claim 13, wherein said gene comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:61 and SEQ ID NO:63.

15. A method of reducing insect infestations, said method comprising introducing into a plant a gene encoding a modified Cry3Bb* polypeptide, wherein said modified Cry3Bb* polypeptide is expressed in an insecticidally effective amount, and wherein said modified Cry3Bb* polypeptide comprises one or more amino acids within loop α7, β1 replaced with one or more amino acids resulting increased flexibility of the loop, wherein said replacement results in one or more amino acid substitutions selected from the group consisting of Tyr287 replaced by phenylalanine, Asp288 replaced by asparagines, Ile289 replaced by threonine or valine, Arg290 replaced by valine, asparagines or leucine, Leu291 replaced by arginine, Tyr292 replaced by phenylalanine, and Ser293 replaced by arginine or proline.

16. The method of claim 15, wherein said gene encodes a modified Cry3Bb* polypeptide selected from the group consisting of SEQ ID NO:14, SEQ ID NO:28, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:62 and SEQ ID NO:64.

17. The method of claim 16, wherein said gene comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:13, SEQ ID NO:27, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:61 and SEQ ID NO:63.