# Patent

## Title
Structure of protein kinase C theta

## Abstract

A three-dimensional structure of human protein kinase C theta (PKCθ) can be used in methods of designing an agent that interacts with PKCθ. The agent can be an inhibitor of PKCθ activity.

## Background
RELATED APPLICATIONS
This application claims the benefit of U.S. Provisional Application No. 60/560,441, filed Apr. 7, 2004, which is incorporated herein by reference in its entirety.


TECHNICAL FIELD
This invention relates to a three-dimensional structure of protein kinase C theta.
BACKGROUND
Protein kinases are mediators of signal transduction in eukaryotic cells that play key roles in physiological processes, development, and homeostasis. Deregulated kinases are present in abnormal cellular physiologies and diseases like cancer. As such, protein kinases are attractive targets for modulating disease pathologies. Serine/threonine kinases represent a significant portion of eukaryotic protein kinases and are broadly classified into six major classes called AGC, CAMK, CMGC, TKL, STE, and CK1. The protein kinase C subfamily belongs to the AKT kinase subfamily of the AGC family.
SUMMARY
A three-dimensional model of protein kinase C theta (PKCθ) can aid in the design of an agent that can interact with PKCθ. In particular, the three-dimensional model can include structural coordinates of atoms of PKCθ. A model including structural coordinates can be used in the structure based design or selection of agents, such as inhibitors or substrates, that interact with PKCθ. A comparison of a three-dimensional model of PKCθ with models of other protein kinases can facilitate the design of an agent that interacts selectively with PKCθ.
In one aspect, a composition includes a crystal including a PKCθ polypeptide. The PKCθ polypeptide can include a catalytic domain of PKCθ. The PKCθ polypeptide can include residues 377-696 of SEQ ID NO:1. The composition can include an agent bound to PKCθ. The agent can be a PKCθ substrate or a PKCθ inhibitor. The PKCθ inhibitor can be staurosporine. The crystal can diffract X-rays to a resolution of at least 2.5 Å, or at least 2.2 Å.
In another aspect, a method of designing an agent that interacts with PKCθ includes generating a three-dimensional model of PKCθ. The three-dimensional model can include structural coordinates of atoms of PKCθ. The three-dimensional model of PKCθ can be a three-dimensional model of a catalytic domain of PKCθ. The structural coordinates can be experimentally determined coordinates. The atoms can be atoms of an active site of PKCθ. The structural coordinates can be according to Table 2, ±a root mean square deviation for alpha carbon atoms of not more than 1.5 Å. The three-dimensional model can include structural coordinates of atoms of an agent. The method can include altering the structure of the agent of the model. The method can include altering the structural coordinates of the agent of the model.
The three-dimensional model can include structural coordinates of an atom selected from the group consisting of atoms of residues Leu386, Gly387, Gly389, Val394, Ala407, Lys409, Val422, Met458, Glu459, Tyr460, Leu461, Gly464, Leu466, Asp508, Asn509, Leu511, Ala521, and Asp522. The three-dimensional model can include structural coordinates of an atom selected from the group consisting of atoms of residues Glu428, Arg503, Asp504, Lys527, Thr536, and Thr538. The three-dimensional model can include structural coordinates of an atom selected from the group consisting of atoms of residues Lys413, Val416, Leu417, Val422, Met426, Lys429, Thr447, Gln449, Leu454, Phe456, Phe691, Arg692, Asn693, Phe694, and Ser695.
The method can include determining a fit between PKCθ and an agent. The method can include calculating a distance between atoms of PKCθ and atoms of agent. The method can include docking a three-dimensional model of an agent to the three-dimensional model of PKCθ. The method can include providing a composition including a PKCθ polypeptide. The PKCθ polypeptide can be crystalline. The composition can include an agent that interacts with PKCθ. The method can include determining a catalytic activity of PKCθ, e.g., a kinase activity of PKCθ. The catalytic activity of PKCθ determined in the presence of the agent can be compared to a catalytic activity of PKCθ determined in the absence of the agent.
In another aspect, a method of identifying an agent capable of altering a catalytic activity of PKCθ includes providing a three-dimensional model of PKCθ, and studying the interaction of a candidate agent with the three-dimensional model of PKCθ. In yet another aspect, a method of identifying an agent capable of altering a catalytic activity of PKCθ includes providing a three-dimensional model of PKCθ including structural coordinates of atoms of PKCθ, studying the interaction of a plurality of candidate agents with the three-dimensional model of PKCθ, and selecting from the plurality of candidate agents an agent which is predicted to alter a catalytic activity of PKCθ.
The interaction of a second candidate agent with the three-dimensional model of PKCθ can be studied. The method can include selecting a candidate agent which is predicted to alter a catalytic activity of PKCθ. A catalytic activity of PKCθ can be measured in the presence of the selected agent.
In another aspect, the invention features a method that includes selecting an agent by performing rational drug design with a three-dimensional structure of a crystal that includes PKCθ. The method includes contacting the agent with PKCθ and detecting the ability of the agent to bind PKCθ.
In another aspect, the invention features a method that includes contacting PKCθ with a ligand to form a composition and crystallizing the composition to form a crystalline complex in which the ligand is bound to PKCθ. The crystalline complex diffracts X-rays to a resolution of at least about 3.5 Å.
In yet another aspect, the invention features a software system that includes instructions for causing a computer system to accept information relating to the structure of PKCθ bound to a ligand, accept information relating to a candidate agent, and determine the binding characteristics of the candidate agent to PKCθ. This determination is based on the information relating to the structure of PKCθ bound to the ligand, and the information relating to the candidate agent.
In another aspect, the invention features a computer program on a computer readable medium on which is stored a plurality of instructions. When the instructions are executed by one or more processors, the processor(s) accept information relating to a structure of PKCθ bound to a ligand and a candidate agent, and determine binding characteristics of the agent to the PKCθ polypeptide. The binding characteristics are determined based on the information relating to the structure of PKCθ and the information relating to the candidate agent.
In another aspect the invention features a method that includes accepting information relating to the structure of a complex including PKCθ bound to a ligand and modeling the binding characteristics of PKCθ to a candidate agent. The method is implemented by a software system, for example.
In another aspect, the invention features a computer program on a computer readable medium on which is stored a plurality of instructions. When the instructions are executed by one or more processors, the processor(s) accept information relating to a structure of a complex including PKCθ bound to a ligand and model the binding characteristics of PKCθ to a candidate agent.
In another aspect, the invention features a software system that includes instructions for causing a computer system to accept information relating to a structure of a complex including PKCθ bound to a ligand and model the binding characteristics of PKCθ to a candidate agent.
In another aspect, the invention features a method of modulating PKCθ activity in a subject including using rational drug design to select an agent that is capable of modulating PKCθ activity and administering a therapeutically effective amount of the agent to the subject.
In another aspect, the invention features a method of treating a subject having a condition associated with PKCθ activity including using rational drug design to select an agent that is capable of affecting PKCθ activity and administering a therapeutically effective amount of the agent to a subject in need of the agent.
In another aspect the invention features a method of prophylactically treating a subject susceptible to a condition associated with PKCθ activity including determining that the subject is susceptible to the condition, using rational drug design to select an agent that is capable of effecting PKCθ activity, and administering a therapeutically effective amount of the agent to the subject.
Structure based modeling can allow the identification of an agent capable of interacting with PKCθ, without the need to experimentally test a large variety of compounds in vivo or in vitro with the goal of identifying a chemical structure that can interact with PKCθ. Such screening can be expensive and time-consuming. Modifications to a known agent that interacts with PKCθ can be examined with structure based design to identify an agent with more desirable properties, such as tighter binding or greater selectivity for PKCθ over other protein kinases, without the need to prepare and test each modified agent.
The details of one or more embodiments are set forth in the accompanying drawings and the description below. Other features, objects, and advantages will be apparent from the description and drawings, and from the claims.



DESCRIPTION OF DRAWINGS
FIG. 1 is a ribbon diagram of human PKCθ complexed with staurosporine.
FIG. 2 is a diagram of staurosporine bound to human PKCθ based on experimental structural coordinates.
FIG. 3A displays the amino acid sequence of full-length human PKCθ (SEQ ID NO:1).
FIG. 3B displays the amino acid sequence of the catalytic domain of human PKCθ with a hexahistidine tag at the C-terminus (SEQ ID NO:2).



DETAILED DESCRIPTION
Protein kinase C theta (PKCθ) and protein kinase B/AKT have been implicated in T cell signaling leading to T cell activation and survival. The expression and role of PKCθ is relatively restricted to T cells, with signaling in response to T cell receptor stimulation contributing to T cell activation and cytokine production. Thus, PKCθ inhibition is desirable in T cell leukemias and T cell mediated autoimmune disorders. See, for example, Fabbro et al., Pharmacology & Therapeutics 93:79-98, 2002; and Altman et al., Immunol. Today 21:567-573, 2000, each of which is incorporated by reference in its entirety.
Members of the PKC subfamily are regulated by calcium, diacylglycerol (DAG), and phorbol esters and can be divided into three groups based on their cofactor requirements: conventional (PKCα, βI, βII, γ), novel (PKCδ, ε, θ, η), and a typical (PKCζ, ι, λ, μ) isoforms (see Arendt et al., Curr. Opin. Immunol. 14:323-330, 2002, which is incorporated by reference in its entirety). These closely related PKC isoenzymes have been shown to have important roles in T cells, B cells, and mast cells contributing to adaptive and innate immunity. They also have diverse roles in cellular functions such as apoptosis, differentiation, motility, insulin resistance, and inflammation. Inhibitors of PKC are currently in clinical trials for various types of cancer.
Three-dimensional structures have been determined for the kinase domain of AKT (PKB) and cAMP dependent PKA, both of which belong to the AGC kinase family (see Huse and Kuriyan, Cell 109:257-282, 2002, which is incorporated by reference in its entirety). It can be desirable to have kinase inhibitors that specifically inhibit only one kinase. The structural similarities between the kinase domain ATP binding sites, however, present a challenge in the development of highly specific inhibitors for use as disease therapies (see Davies et al., Biochem. J. 351:95-105, 2000, which is incorporated by reference in its entirety). Structural elucidation of kinase active sites and those of closely related family members can increase understanding of inhibitor selectivity and the mechanism of enzyme action. In addition, structural information can aid the rational design and optimization of small molecule inhibitors as therapeutics for T cell mediated allergic and autoimmune diseases.
Structural coordinates are Cartesian coordinates that describe the location of atoms in three-dimensional space in relation to other atoms in a molecule or molecular complex. Structural coordinates may be obtained by using, for example, X-ray crystallography techniques or NMR techniques. Additional structural information can be obtained from spectral techniques (e.g., optical rotary dispersion (ORD), circular dichroism (CD)), homology modeling, and computational methods such as those that include data from molecular mechanics or from dynamics assays.
Various software programs allow for the graphical representation of a set of structural coordinates to obtain a representation of a molecule or molecular complex, such as PKCθ bound to staurosporine. In general, such a representation should accurately reflect (relatively and/or absolutely) structural coordinates, or information derived from structural coordinates, such as distances or angles between features. The representation can be a two-dimensional figure, such as a stereoscopic two-dimensional figure, or an interactive two-dimensional display (e.g., a computer display that can display different faces of the molecule or molecular complex), or an interactive stereoscopic two-dimensional display. The coordinates can be used to direct the creation of a physical three-dimensional representation of the molecule or molecular complex, such as a ball-and-stick model or a model prepared by rapid prototyping. The structural coordinates may be modified by mathematical manipulation, such as by inversion or integer additions or subtractions. As such, the structural coordinates are relative coordinates, and are in no way specifically limited by the actual x, y, z coordinates of Table 2.
A three-dimensional molecular model is a representation of a molecule or molecular complex. A three-dimensional model can be a physical model of a molecular structure (e.g., a ball-and-stick model), or a graphical representation of a molecular structure. A graphical representation can include, for example, a drawing or a figure presented on a computer display. A two-dimensional graphical representation (e.g., a drawing) can be a three-dimensional model when the two-dimensional representation reflects three-dimensional information, for example, through the use of perspective, shading, or the obstruction of features more distant from the viewer by features closer to the viewer. Preferably, the graphical representation accurately reflects structural coordinates, or information derived from structural coordinates, such as distances or angles between features of the model. When the three-dimensional model includes a polypeptide, such as a PKCθ polypeptide, the model can include one or more different levels of structure, such as primary structure (amino acid sequence), secondary structure (e.g., α-helices and β-sheets), tertiary structure (overall fold), and quarternary structure (oligomerization state). A model can include different levels of detail. For example, the model can include the relative locations of secondary structural features of a protein without specifying the positions of atoms. A more detailed model can include the positions of atoms.
The model can include features derived from the structural coordinates and other chemical information. For example, the shape of a solvent accessible surface can be derived from structural coordinates, the van der Waals radii of the atoms of the model, and the van der Waals radius of a solvent (e.g., water). Other features that can be derived from structural coordinates include without limitation, electrostatic potential, the location of voids or pockets within a macromolecular structure, and the location of hydrogen bonds and salt bridges.
The model can include structural coordinates of atoms in the molecular structure. Structural coordinates can be experimentally determined, for example by X-ray crystallography or NMR spectroscopy, or can be generated by, for example, homology modeling. The molecular structure can include a single molecule, a portion of a molecule, a complex of two or more molecules, a group of molecules, or a combination thereof. In a model of a molecular complex, the molecules can be associated by covalent or non-covalent bonds, including, for example, hydrogen bonds, hydrophobic interactions, or electrostatic attraction. A molecular complex can include tightly associated molecules, such as an enzyme/inhibitor complex, and loosely associated molecules, such as a crystalline compound having ordered solvent molecules or ions present in the crystal. A model can include, for example, a complex of a protein bound to an agent, such as, for example, a complex of an enzyme bound to an inhibitor. When the model includes structural coordinates, coordinates of some atoms in a molecule can be omitted.
Conservative substitutions are amino acid substitutions which are functionally or structurally equivalent to the substituted amino acid residue. A conservative substitution can include switching one residue for another with similar polarity, steric arrangement, or belonging to the same class (e.g., hydrophobic, acidic or basic) as the substituted residue. Conservative substitutions include substitutions having an inconsequential effect on the three-dimensional structure of PKCθ with respect to identification and design of agents that interact with PKCθ, as well as for molecular replacement analyses or homology modeling.
An agent includes a protein, polypeptide, peptide, nucleic acid (including DNA or RNA), molecule, compound or drug. An agent can act as a substrate, inhibitor, activator, allosteric effector, or binding partner with an enzyme.
An active site is a region of a molecule or molecular complex that can interact or associate with an agent (including, without limitation, a protein, polypeptide, peptide, nucleic acid, including DNA or RNA, molecule, compound or drug). An active site may include, for example, the site of agent binding, as well as accessory binding sites adjacent or proximal to the actual site of binding that may affect activity upon interaction or association with a particular agent. The active site can include a site of inhibitor binding. The inhibitor can inhibit either by direct interference with the actual site of substrate binding (i.e., by competing for substrate binding) or by indirectly affecting the steric conformation or charge potential, thereby preventing or reducing binding of substrate at the actual site of substrate binding. For example, an active site can be a site of cofactor binding, substrate binding (e.g., the substrate to be phosphorylated) or inhibitor binding. An active site can include a site of allosteric effector binding, or a site of phosphorylation, glycosylation, alkylation, acylation, or other covalent modification.
Root mean square deviation (rms deviation, or rmsd) is the square root of the arithmetic mean of the squares of the deviations from the mean, and is a way of expressing deviation or variation from structural coordinates. Conservative substitutions of amino acid residues can result in a molecular model having structural coordinates within the stated root mean square deviation. In particular, two molecular models of polypeptides that differ from one another by conservative substitutions can have coordinates of backbone atoms within a stated rms deviation, such as less than 1.5 Å, less than 1.0 Å, or less than 0.5 Å. Backbone atoms of a polypeptide include the alpha carbon (Cα or CA) atoms, carbonyl carbon (C) atoms, carbonyl oxygen (O) atoms, and amide nitrogen (N) atoms.
The numbering of the amino acid residues of PKCθ may be different than set forth here, and may contain certain conservative amino acid substitutions, additions or deletions that yield the same three-dimensional structures as those defined by Table 2, ± an rmsd for backbone atoms of less than 1.5 Å. Corresponding amino acids and conservative substitutions in other isoforms or analogs are easily identified by visual inspection of the relevant amino acid sequences or by using commercially available homology software programs (e.g., MODELLAR, MSI Management Simulations, Inc. San Diego, Calif.). An isoform is any of several multiple forms of a protein that differ in their primary structure. An analog is a polypeptide having conservative amino acid substitutions.
“PKCθ” refers to a PKCθ protein or nucleic acid (e.g., a DNA or RNA), or a fragment thereof. In some embodiments, a fragment of PKCθ can include, for example, only the N-terminal domain of the protein, only the C-terminal domain of the protein, or a fragment of either domain of the protein. In another embodiment, a fragment of PKCθ can include both the N-terminal domain and the C-terminal domain. The PKCθ protein or nucleic acid can originate from a nonmammalian or mammalian species. Mammalian PKCθ can originate from a human, for example. Exemplary nonhuman mammals include, a nonhuman primate (such as a monkey or ape), a mouse, rat, goat, cow, bull, pig, horse, sheep, wild boar, sea otter, cat, or dog. Exemplary nonmammalian species include a chicken, turkey, shrimp, alligator, or fish.
PKCθ includes an N-terminal domain and a C-terminal catalytic domain. The N-terminal domain consists of multiple modules and functions as a regulatory domain (see, for example, Newton, A. C., Biochem. J. 370, 361-371, 2003, which is incorporated by reference in its entirety). The C-terminal catalytic domain can be expressed from a DNA plasmid as a soluble, active protein, for example, including residues 362-706 of the full-length sequence of human PKCθ. The expression can be driven by a promoter, such as an inducible promoter. FIG. 3A displays the full-length sequence of PKCθ, and FIG. 3B the sequence of residues 362-706 of the catalytic domain with an added C-terminal hexahistidine tag. Other polypeptide sequences than the one shown in FIG. 3B can be used, for example, sequences having additional or fewer residues of the full-length PKCθ sequence at the N-terminus, or sequences having fewer residues at the C-terminus. In some embodiments, PKCθ can be expressed as a fusion protein with a tag other than hexahistadine, such as a glutathione-S-transferase (GST), myc, HA, Strep or FLAG tag. The tag can facilitate isolation of PKCθ from cells, such as from bacterial cells or from a mammalian cell line. For example, PKCθ can be expressed in and isolated from E. coli cells. A fusion protein can be cleaved at a protease site engineered into the fusion protein, such as at or near the site of fusion between the polypeptide and the tag. When it is desirable to form a complex between PKCθ and a ligand, such as staurosporine (a natural product kinase inhibitor), PKCθ can be contacted with the ligand following cleavage and purification. For example, PKCθ can be mixed with staurosporine prior to purification (e.g., prior to cleavage of a polypeptide tag), or PKCθ can be mixed with staurosporine after purification. In some embodiments, staurosporine can be mixed with PKCθ prior to purification and again following purification.
PKCθ can be placed in solution for collecting spectral data or NMR data, or for growing a crystal. For example, PKCθ can be crystallized in the presence of a salt (e.g., a sodium salt), a polymer (e.g., polyethylene glycol (PEG)), and/or an organic solvent. Crystals can be grown by various methods, such as, for example, sitting or hanging drop vapor diffusion. In general, crystallization can be performed at a temperature of from about 4° C. to about 60° C. (e.g., from about 4° C. to about 45° C., such as at about 4° C., about 15° C., about 18° C., about 20° C., about 25° C., about 30° C., about 32° C., about 35° C., about 37° C.).
The C-terminal catalytic domain of PKCθ can be crystallized as a complex with an agent. In particular, it can be crystallized as a 1:1 complex with staurosporine (a natural product kinase inhibitor), from a solution including NaCl, MgCl2, dithiothreitol (DTT), and Tris buffer. The solution can include a precipitant, such as ammonium sulfate. A crystal of PKCθ can belong to space group C2, with dimensions a=139.6 Å, b=42.4 Å, c=67.7 Å, and β=116.2°. The space group refers to overall symmetry of the crystal, and includes point symmetry and space symmetry. In certain embodiments, a crystal of PKCθ bound to staurosporine can contain one molecule of PKCθ in the asymmetric unit. The asymmetric unit is the smallest unit from which the crystal structure can be generated by making use of the symmetry operations of the space group. A crystal is generally made up of the motif defined by the space-group symmetry operations on the asymmetric units, and a translation of that motif through the crystal lattice.
In general, a crystal of PKCθ bound to staurosporine can diffract X-rays to a resolution of about 3.5 Å or less (e.g., about 3.2 Å or less, about 3.0 Å or less, about 2.5 Å or less, about 2.4 Å or less, about 2.3 Å or less, about 2.2 Å or less, about 2.1 Å or less, about 2.0 Å or less, about 1.9 Å or less, about 1.8 Å or less, about 1.7 Å or less, about 1.6 Å or less, about 1.5 Å or less, about 1.4 Å or less). In some embodiments, the crystal can diffract X-rays to a resolution of from about 1.6 to about 2.5 Å (e.g., from about 1.8 to about 2.2 Å).
Structural data describing a crystal can be obtained, for example, by X-ray diffraction. X-ray diffraction data for the crystals can be collected by a variety of means in order to obtain structural coordinates. Suitable X-ray sources include rotating anode and synchrotron sources (e.g., Advanced Light Source (ALS), Berkeley, Calif.; or Advanced Photon Source (APS), Argonne, Ill.). In certain embodiments, X-rays for generating diffraction data can have a wavelength of from about 0.5 Å to about 1.6 Å (e.g., about 0.7 Å, about 0.9 Å, about 1.0 Å, about 1.1 Å, about 1.3 Å, about 1.4 Å, about 1.5 Å, about 1.6 Å). Suitable X-ray detectors include area detectors and charge-couple devices (CCDs). X-ray diffraction data of a crystal of a complex of PKCθ bound to staurosporine can be used to obtain the structural coordinates of the atoms in the complex.
In some embodiments, the X-ray diffraction data can be used to construct an electron density map of PKCθ bound to staurosporine, and the electron density map can be used to derive a representation (e.g., a two dimensional representation, a three dimensional representation) of a complex including PKCθ bound to staurosporine, or a fragment of the complex. Creation of an electron density map typically involves using information regarding the phase of the X-ray scatter. Phase information can be extracted, for example, either from the diffraction data or from supplementing diffraction experiments to complete the construction of the electron density map. Methods for calculating phase from X-ray diffraction data, include, without limitation, multiwavelength anomalous dispersion (MAD), multiple isomorphous replacement (MIR), multiple isomorphous replacement with anomalous scattering (MIRAS), reciprocal space solvent flattening, molecular replacement, and single isomorphous replacement with anomalous scattering (SIRAS), or a combination thereof. These methods generate phase information by making isomorphous structural modifications to the native protein, such as by including a heavy atom or changing the scattering strength of a heavy atom already present, and then measuring the diffraction amplitudes for the native protein and each of the modified cases. If the position of the additional heavy atom or the change in its scattering strength is known, then the phase of each diffracted X-ray can be determined by solving a set of simultaneous phase equations. The location of heavy atom sites can be identified using a computer program, such as SHELXS (Sheldrick, Institut Anorg. Chemie, Göttingen, Germany), and diffraction data can be processed using computer programs such as MOSFLM, SCALA, SOLOMON, and SHARP (“The CCP4 Suite: Programs for Protein Crystallography,” Acta Crystallogr. Sect. D, 54:905-921, 1997; deLa Fortelle and Brigogne, Meth. Enzym. 276:472-494, 1997). Upon determination of the phase, an electron density map of the complex can be constructed.
The electron density map can be used to derive a representation of a polypeptide, a complex, or a fragment of a polypeptide or complex by aligning a three-dimensional model of a polypeptide or complex (e.g., a complex containing a polypeptide bound to a ligand) with the electron density map. For example, the electron density map corresponding to PKCθ bound to staurosporine can be aligned with a previously determined electron density map corresponding to an unbound TPK1δ polypeptide from Saccharomyces cerevisiae. The electron density map can be further aligned by aligning it with an electron density map created from a collection of similar structures (e.g., a collection or 5, 6, or 7 protein kinase structures) overlayed to generate an “average” electron density map.
The alignment process results in a comparative model that shows the degree to which the calculated electron density map varies from the model of the previously known polypeptide or the previously known complex. The comparative model is then refined over one or more cycles (e.g., two cycles, three cycles, four cycles, five cycles, six cycles, seven cycles, eight cycles, nine cycles, 10 cycles) to generate a better fit with the electron density map. A software program such as CNS (Brunger et al., Acta Crystallogr. D54:905-921, 1998) can be used to refine the model. The quality of fit in the comparative model can be measured by, for example, an Rwork or Rfree value. A smaller value of Rwork or Rfree generally indicates a better fit. Misalignments in the comparative model can be adjusted to provide a modified comparative model and a lower Rwork or Rfree value. The adjustments can be based on information (e.g., sequence information) relating to other known protein kinase polypeptides (e.g., a TKP1δ polypeptide), a human PKCθ polypeptide, staurosporine, or a human PKCθ polypeptide/staurosporine complex. As an example, in embodiments in which one or more models of previously known protein kinases are used, such as a structural model of a TKP1δ polypeptide, an adjustment can include replacing an amino acid in the previously known protein kinase polypeptide with the amino acid in the corresponding site of a different protein kinase (e.g., the human PKCθ polypeptide). When adjustments to the modified comparative model satisfy a best fit to the electron density map, the resulting model is that which is determined to describe the polypeptide or complex from which the X-ray data was derived. Methods of such processes are disclosed, for example, in Carter and Sweet, eds., “Macromolecular Crystallography” in Methods in Enzymology, Vol. 277, Part B, New York: Academic Press, 1997, and articles therein, e.g., Jones and Kjeldgaard, “Electron-Density Map Interpretation,” p. 173, and Kleywegt and Jones, “Model Building and Refinement Practice,” p. 208.
Discussed above is a method of deriving a representation of a complex by aligning a three-dimensional model of a previously known polypeptide or a previously known complex with a newly calculated electron density map corresponding to a crystal of the polypeptide or the complex. One adjustment that can be used in this modeling process can include replacing the compound in the representation of the previously known complex with staurosporine.
As described above, a three-dimensional model of PKCθ including structural coordinates can be derived from X-ray diffraction data of a PKCθ/staurosporine crystal. The structural coordinates of one such model are shown below in Table 2. A three-dimensional model can include structural coordinates of a portion of PKCθ (for example, a structural core of PKCθ, or an active site of PKCθ) according to Table 2, ±a root mean square deviation from the alpha carbon atoms of amino acids of not more than 1.5 Å, preferably not more than 1.0 Å, and most preferably not more than 0.5 Å. The three-dimensional model of PKCθ is useful for a number of applications, including, but not limited to, the visualization, identification and characterization of various active sites of PKCθ. The active site structures may then be used to design agents that interact with PKCθ.
A machine, such as a computer, can be programmed in memory with the structural coordinates of a PKCθ model, together with a program capable of generating a three-dimensional graphical representation of the structural coordinates on a display connected to the machine. Alternatively or additionally, a software system can be designed and/or utilized to accept and store the structural coordinates. The software system can be capable of generating a graphical representation of the structural coordinates. The software system can also be capable of accessing external databases to identify compounds with similar structural features as staurosporine, and/or to identify one or more candidate agents with characteristics that may render the candidate agent(s) likely to interact with PKCθ.
A machine having a memory containing such data or a software system containing such data can aid in the rational design or selection of inhibitors or activators of PKCθ activity, including the evaluation of the ability of an agent to associate with PKCθ or a PKCθ complex, as well as in the modeling of compounds or proteins related by structural or sequence homology to PKCθ. For example, such a machine or software system can aid in the evaluation of the ability of an agent to associate with PKCθ, or can aid in the modeling of compounds or proteins related by structural or sequence homology to PKCθ. As used herein, an activator, or agonist, refers to a compound that enhances at least one activity of PKCθ, and an inhibitor, or antagonist, refers to a compound that inhibits at least one activity, or has an opposite activity, of a human PKCθ polypeptide. For example, a compound, such as staurosporine can function as an antagonist of a human PKCθ polypeptide by decreasing the rate of PKCθ kinase activity in T cells.
The machine can produce a representation (e.g., a two dimensional representation or a three-dimensional representation) of PKCθ, a portion thereof (such as a portion including an active site or a binding site), a PKCθ/staurosporine complex, or a PKCθ analog. A software system, for example, can cause the machine to produce such information. The machine can include a machine-readable data storage medium comprising a data storage material encoded with machine-readable data. The machine-readable data can include structural coordinates of atoms of PKCθ or PKCθ bound to staurosporine. Machine-readable storage media including data storage material can include conventional computer hard drives, floppy disks, DAT tape, CD-ROM, DVD, and other magnetic, magneto-optical, optical, and other media which may be adapted for use with a computer. The machine can also have a working memory for storing instructions for processing the machine-readable data, as well as a central processing unit (CPU) coupled to the working memory and to the machine-readable data storage medium for the purpose of processing the machine-readable data into the desired three-dimensional representation. Finally, a display can be connected to the CPU so that the three-dimensional representation may be visualized by the user. Accordingly, when used with a machine programmed with instructions for using said data, (e.g., a computer loaded with one or more programs of the sort described herein) the machine is capable of displaying a graphical representation (e.g., a two-dimensional graphical representation, a three-dimensional graphical representation) of any of the molecules or molecular complexes, or portions of molecules of molecular complexes, described herein.
An active site of PKCθ can include an inhibitor binding site, such as a staurosporine binding site. An active site of PKCθ can include one or more of amino acid residues Leu386, Gly387, Gly389, Val394, Ala407, Lys409, Val422, Met458, Glu459, Tyr460, Leu461, Gly464, Leu466, Asp508, Asn509, Leu511, Ala521, and Asp522 (see FIGS. 3A and 3B). An active site can include amino acid residues belonging to the activation segment, residues 522-543, or residues that interact with the activation segment, such as Glu428, Arg503, Asp504, Lys527, Thr536, and Thr538. An active site of PKCθ can include amino acid residues of the hydrophobic motif, or amino acid residues that interact with the hydrophobic motif, such as Lys413, Val416, Leu417, Val422, Met426, Lys429, Thr447, Gln449, Leu454, Phe456, Phe691, Arg692, Asn693, Phe694, and Ser695. An active site of PKCθ can be described by structural coordinates. The structural coordinates can be adjusted±a root mean square deviation for the alpha carbon atoms of amino acids of not more than 1.5 Å, preferably not more than 1.0 Å, and most preferably not more than 0.5 Å. The active site can be described by the structural coordinates in Table 2 (see below).
An agent that interacts with (e.g., binds) PKCθ can be identified or designed by a method that includes using a representation of PKCθ, such as a three-dimensional model of PKCθ bound to staurosporine. The model can be a model of a PKCθ analog having conservative substitutions from the PKCθ amino acid sequence. Preferably the model includes structural coordinates of atoms of PKCθ. The structural coordinates can be, for example, the coordinates in Table 2, optionally adjusted±a root mean square deviation for the alpha carbon atoms of PKCθ of not more than 1.5 Å, not more than 1.0 Å, or not more than 0.5 Å. In the method, a three-dimensional model is generated using structural coordinates of PKCθ bound to staurosporine. The model can include a portion of PKCθ, such as an active site. A candidate agent that interacts with the model can then be designed or identified by performing computer fitting analysis of the candidate agent with the three-dimensional model.
A display (e.g., a computer display) can show a representation of a three-dimensional model of PKCθ, for example, a diagram of an active site of PKCθ, to a user. The model can include an agent bound to PKCθ, or the user can superimpose a three-dimensional model of an agent on the PKCθ model. The agent can be, for example, a substrate or inhibitor of PKCθ, a candidate substrate or candidate inhibitor. The agent in the model can be a known compound, a novel chemical structure, or a fragment of a chemical structure. The user can inspect the resulting three-dimensional model of a PKCθ/agent complex. A three-dimensional model of a PKCθ/agent complex can also be generated, for example, by altering, a previously existing PKCθ/agent complex model, such as a model of a PKCθ/staurosporine complex. It can be desirable for the agent to fit the active site closely. In other words, the agent can have a shape that complements the shape of the active site. There can be a preferred distance, or range of distances, between atoms of the agent and atoms of PKCθ. Distances longer than a preferred distance may be associated with a weak interaction between the agent and PKCθ (e.g., an active site of PKCθ). Distances shorter than a preferred distance may be associated with repulsive forces that can weaken the interaction between the agent and PKCθ. A steric clash can occur when distances between atoms are too short. A steric clash occurs when the locations of two atoms are unreasonably close together, for example, when two atoms are separated by a distance less than the sum of their van der Waals radii. If a steric clash exists, the user can adjust the position of the agent relative to PKCθ (e.g., a rigid body translation or rotation of the agent) until the steric clash is relieved. The user can adjust the conformation of the agent or of PKCθ in the vicinity of the agent in order to relieve a steric clash. Steric clashes can also be removed by altering the structure of the agent, for example, by changing a bulky group, such as an aromatic ring, to a smaller group, such as to a methyl or hydroxyl group, or by changing a-rigid group to a flexible group that can accommodate a conformation that does not produce a steric clash. Electrostatic forces can also influence an interaction between an agent and an active site. For example, electrostatic properties can be associated with repulsive forces that can weaken the interaction between the agent and PKCθ. Electrostatic repulsion can be relieved by altering the charge of the agent, e.g., by replacing a positively charged group with a neutral group.
Forces that influence binding strength between the agent and PKCθ can also be evaluated in the PKCθ/agent model. These can include, but are not limited to, hydrogen bonding, electrostatic forces, hydrophobic interactions, van der Waals interactions, dipole-dipole interactions, π-stacking forces, and cation-π interactions. The user can evaluate these forces visually, for example by noting a hydrogen bond donor/acceptor pair arranged with a distance and angle suitable for a hydrogen bond. Based on the evaluation, the user can alter the model to find a more favorable interaction between PKCθ and the agent. Altering the model can include changing the three-dimensional structure of PKCθ without altering its chemical structure, for example by altering the conformation of amino acid side chains or backbone dihedral angles. Altering the model can include altering the position or conformation of the agent, as described above. Altering the model can also include altering the chemical structure of the agent, for example by substituting, adding or removing groups. For example, if a hydrogen bond donor on PKCθ is located near a hydrogen bond donor on the agent, the user can replace the hydrogen bond donor on the agent with a hydrogen bond acceptor.
The relative locations of the agent and PKCθ, or their conformations, can be adjusted to find an optimized binding geometry for a particular agent to PKCθ. An optimized binding geometry is characterized by, for example, favorable hydrogen bond distances and angles, maximal electrostatic attractions, minimal electrostatic repulsions, the sequestration of hydrophobic moieties away from an aqueous environment, and the absence of steric clashes. The optimized geometry can have the lowest calculated energy of a family of possible geometries for a PKCθ/agent complex. An optimized geometry can be determined, for example, through molecular mechanics or molecular dynamics calculations.
A series of models (e.g., two dimensional models, three-dimensional models) of PKCθ/agent complexes having different bound agents can be generated. A score can be calculated for each model of a PKCθ/agent complex in the series. The score can describe, for example, an expected strength of interaction between PKCθ and the agent. The score can reflect one of the factors described above that influence binding strength described above. The score can be an aggregate score that reflects more than one of the factors. The different agents can be ranked according to their scores.
Steps in the design of the agent can be carried out in an automated fashion by a machine (e.g., a computer). For example, a model of a PKCθ active site can be programmed in the machine, along with models of a series of candidate agents. The machine can find an optimized binding geometry for each of the candidate agents to the PKCθ active site, and calculate a score to determine which of the agents in the series is likely to interact most strongly with PKCθ.
A software system can be designed and/or implemented to facilitate these steps. Software systems (e.g., computer programs) used to generate such three-dimensional models or perform the necessary fitting analyses include, but are not limited to: MCSS, Ludi, QUANTA® (macromolecular X-ray crystallography software), Insight II® (biological compound modeling and simulation software), Cerius2® (modeling and simulation software), CHARMm® (software for simulation of biological macromolecules), and Modeler from Accelrys, Inc. (San Diego, Calif.); SYBYL® (molecular modeling software), Unity, FleXX, and LEAPFROG from TRIPOS, Inc. (St. Louis, Mo.); AUTODOCK (Scripps Research Institute, La Jolla, Calif.); GRID (Oxford University, Oxford, UK); DOCK (University of California, San Francisco, Calif.); and Flo+ and Flo99 (Thistlesoft, Morris Township, N.J.). Other useful programs include ROCS, ZAP, FRED, Vida, and Szybki from Openeye Scientific Software (Santa Fe, N.Mex.); Maestro, Macromodel, and Glide from Schrodinger, LLC (Portland, Oreg.); MOE (Chemical Computing Group, Montreal, Quebec), Allegrow (Boston De Novo, Boston, Mass.), CNS (Brunger, et al., Acta Crystall. Sect. D 54:905- 921, 1997) and GOLD (Jones et al., J. Mol. Biol. 245:43-53, 1995). The structural coordinates can also be used to visualize the three-dimensional structure of PKCθ using MOLSCRIPT, RASTER3D, or PYMOL (Kraulis, J. Appi. Crystallogr. 24: 946-950, 1991; Bacon and Anderson, J. Mol. Graph. 6: 219-220, 1998; DeLano, The PYMOL Molecular Graphics System (2002) DeLano Scientific, San Carlos, Calif.).
The agent, whether an inhibitor or activator, may be selected by screening an appropriate database, may be designed de novo by analyzing the steric configurations and charge potentials of an empty PKCθ active site in conjunction with the appropriate software programs, or may be designed using characteristics of known inhibitors or activators to PKCθ or other protein kinases. The method can be used to design or select PKCθ inhibitors or activators. A software system can be designed and/or implemented to facilitate database searching, and/or agent selection and design.
Once an agent has been designed or identified, it may be obtained or synthesized and further evaluated for its effect on PKCθ activity. For example, the agent may be evaluated by contacting the identified agent with PKCθ and measuring the effect of the agent on PKCθ activity. A method for evaluating the agent can include an activity assay performed in vitro or in vivo. For example, the agent can be evaluated by contacting it with PKCθ and measuring the effect of the agent on kinase activity by the polypeptide. Agents can be assessed by their ability to increase or decrease the ability of PKCθ to phosphorylate a peptide substrate, such as a biotinylated peptide substrate FRAKGSLFQ. Reactions can include labelled ATP (e.g., 33P-ATP), and kinase activity can be monitored by measuring the resulting levels of labelled peptide substrate.
An activity assay, such as a kinase activity assay, can be performed in vivo. For example, the assay can be a cell-based assay.
Depending upon the action of the agent on PKCθ, the agent may act either as an inhibitor or activator of PKCθ activity. The agent also may be contacted with PKCθ in the presence of staurosporine in order to determine whether or not the agent inhibits binding between PKCθ and staurosporine. A crystal containing PKCθ bound to the identified agent can be grown and the structure determined by X-ray crystallography. A second agent can be designed or identified based on the interaction of the first agent with PKCθ.
Various molecular analysis and rational drug design techniques are further disclosed in, for example, U.S. Pat. Nos. 5,834,228, 5,939,528 and 5,856,116, as well as in PCT Application No. PCT/US98/16879, published WO 99/09148, the contents of which are hereby incorporated by reference.
While certain embodiments have been described, other embodiments are also contemplated. As an example, while embodiments involving PKCθ bound to staurosporine have been described, the description herein is more generally directed to any PKCθ polypeptide and any ligand.
EXAMPLE
The C-terminal catalytic domain of human PKCθ, from residue 362 to residue 706, was cloned into a pET-16b expression vector. This vector introduced a hexa-histidine tag to the C-terminus of the expressed protein (see FIG. 3B). The plasmid was used to transform E. coli strain BL21-DE3 for overexpression. A 10-liter cell culture was expanded at 37° C. to an OD600 of about 0.4. The temperature was then lowered to 25° C. before addition of IPTG to a final concentration of 0.1 mM to induce expression. The cells were grown for an additional 4 hours before they were harvested.
Harvested cells were resuspended in 25 mM Tris pH 8.0, 25 mM NaCl, 5 mM 2-mercaptoethanol, 5 mM imidazole, 50 μM ATP and protease inhibitors, and lysed using a microfluidizer. The lysate was applied to 20 mL of Nickel-NTA resin for 1 hour at 4° C. The resin was subsequently poured as a chromatography column and washed extensively with the same buffer including 25 mM imidazole. Protein bound to the resin was eluted with 200 mM imidazole buffer. The protein was then immediately loaded onto an anion exchanger HQ (high capacity quaternized polyethyleneimine) and the column was washed with 25 mM Tris pH 8.0, 25 mM NaCl, 5 mM DTT, 50 μM ATP before being resolved by the application of a linear gradient from 25 mM to 500 mM NaCl. Fractions containing PKCθ were selected by SDS-PAGE, pooled, and diluted two-fold with 25 mM Tris pH 8.0, 5 mM DTT and loaded onto a heparin chromatography column. The flow-through was immediately applied to a hydroxy-apatite column and washed extensively with 25 mM Tris pH 8.0, 50 mM NaCl, 5 mM DTT. A linear gradient of sodium phosphate from 0 to 100 mM eluted the target protein. The protein was then sized as a monomer on a Superdex 200 size exclusion chromatography column, dialyzed overnight against 25 mM Tris pH 8.0, 50 mM NaCl, 5 mM DTT and concentrated to 7 mg/mL (determined by Bradford assay) before being used for crystallization experiments. The staurosporine was added at a 1:1.2 molar ratio in excess to PKCθ before the final concentration step.
Bacterial extracts expressing the kinase domain were prepared and analyzed for kinase activity in vitro with 5 μg protein each, with a final concentration of 83 μM biotinylated peptide substrate (FRAKGSLFQ) (SEQ ID NO:3), 166 μM ATP, 0.5 μL of 33P ATP (specific activity 3000 Ci/mmol, 10 mCi/mL), 84 ng/μL phosphatidylserine, 8.4 ng/μL diacylglycerol in 20 mM MOPS pH 7.2, 2 5mM β-glyceraldehyde, 1 mM sodium orthovanadate, 1 mM DTT, 1 mM CaCl2 in a final volume of 30 μL for 30 minutes at room temperature. Purified kinase was assayed for activity using 4-10 nM kinase domain in similar radioactive kinase assays. Kinase reactions were stopped by addition of buffer containing EDTA and transferred to streptavidin-coated scintiplates for washing and radioactivity detection in a plate reader. Alternatively, 5 to 10 μL of the reaction mixture was spotted on phosphocellulose paper and washed three times in 0.75% phosphoric acid and once in acetone. Scintillation cocktail was added to the phosphocellulose paper and bound radioactivity was detected with a scintillation counter. The radioactivity associated with peptide-only and kinase-only control reactions was subtracted from final counts as background.
The solution of PKCθ with staurosporine was concentrated to 7 mg/mL in 50 mM NaCl, 5 mM MgCl2, 5 mM DTT, 25 mM Tris-HCl buffer, at pH 8.0. Crystals were obtained from hanging drops at 18° C. The drop contained 1 μL of protein solution and 1 μL of precipitating solution. The precipitating solution was 2 M ammonium sulfate, 40 mM DTT and 0.1 M Bis-tris, pH 5.0. Crystals were stabilized in cryo-solution containing the crystallization reagent plus 25% glycerol, mounted in nylon loops and flash-frozen in a 100 K nitrogen stream. The X-ray diffraction data were collected to 2 Å resolution at the Advanced Light Source (Berkeley, Calif.) using a Quantum-4 CCD detector (Area Detector Systems), then reduced using HKL2000 software (see Otwinowski and Minor, Methods Enzymol. 276:307-326, 1997, which is incorporated by reference in its entirety). Statistics of data collection are given in Table 1.
A sequence alignment showed that human PKCθ and TPK1δ, a cAMP-dependent protein kinase catalytic subunit from Saccharomyces cerevisiae, have a sequence identity of 42% and secondary structure similarity of 63%. Phases were calculated by molecular replacement using AMORE with the structure of TPK1δ (Protein Data Bank code 1FOT) as a search model (see Acta Cryst. D50, 1994; and Mashhoon et al., Arch. Biochem. Biophys. 387:11-19, 2001, each of which is incorporated by reference in its entirety). The rotation and translation function solutions were found using data from 8 to 3.5 Å. The BUSTER program and TNT were used in generating maximum entropy omit maps to reduce model bias and to produce a more detailed map for the bound inhibitor (see Bricogne, Acta Cryst. D49:37-60, 1993; and Tronrud, Methods in Enzymology 277B, 1997, each of which is incorporated by reference in its entirety). Some residues in the N-lobe, and all flex loops, fit the map poorly. In order to overcome the model bias and to generate better maps for the PKCθ model, an ‘average map’ was calculated by overlapping seven protein kinase coordinates including those from the 1FOT.pdb data file. The CNS program was used to calculate the average map (see Brunger et al., Acta Cryst. D54:905-921, 1998, which is incorporated by reference in its entirety). The resulting electron density maps were more easily interpreted, especially for loop regions in the N-lobe. The model was further rebuilt and refined, and the quality of the model was judged by the decrease in R-factor, Rfree, as well as how the residues fit the maps. Refinement converged after many rebuilding cycles to an R-factor of 0.201 and Rfree of 0.216. The refinement statistics are given above in Table 1. The final model included coordinates of residues Ile377-Pro649 and Gln688-Phe696, two phosphate groups (as phosphoserine and phosphothreonine, see below), 115 ordered water molecules and one staurosporine molecule. The first 12 residues at the N-terminus, C-terminal region Pro650-Asp687, and the last 10 residues at the C-terminus were not included in the model due to their electron density disorder.







TABLE 1





Statistics of X-Ray Diffraction Data Collection







Crystal and data collection










Crystal system
monoclinic



Space group
C2



Unit cell dimensions (Å)
a = 139.6, b = 42.4, c = 67.7,




β = 116.2°



Data collection temperature
100 K



Number of crystals
1



Radiation source
ALS, Berkeley, CA



X-ray wavelength
1.0 Å



Crystal mosaicity
0.63°



Maximum resolution (Å)
2.0



Rmerge
5.8%







Phasing and refinement










Model for molecular refinement
1FOT.pdb (TPK1δ, PKA)



Construct (aa)
PKCθ 362-706



Refined model (aa)
377-649, 688-696



Number atoms (protein)
2353



Water molecules
115



Phosphorylation sites
Thr538, Ser695



Compound (inhibitor)
1 staurosporine



PKCθ molecules
1



per asymmetric unit



Resolution range
20-2.0 Å



Rcryst
0.201 (19445 reflections)



Rfree
0.216 (818 reflections)



R.m.s. deviations from
0.005



ideal bond lengths



R.m.s. deviations from
1.082°



ideal bond angles










The structural coordinates of the refined model are presented below in Table 2. In Table 2, the “#” column assigns an index to each atom for which coordinates are given. The “name” column indicates what type of atom, and the “res” column indicates what type of residue the atom belongs to. The “chain” indicates which polypeptide the atom belongs to. “Res #” gives the residue number for the atom. For example, atom number 1 (the first row in Table 2) is the beta carbon (CB) of Ile377. Its x, y, and z structural coordinates are given in the X, Y, and Z columns, respectively. The column headed “occ” describes the occupancy assigned to the atom (1.00=full occupancy), and the “B” column provides B factors (or temperature factors) in units of Å2. Coordinates of bound staurosporine are denoted with the entry “STU” in the res column, and phosphothreonine and phosphoserine are denoted by “TPB” and “SPB,” respectively.
The overall fold of the catalytic domain of PKCθ was similar to other protein kinases, including those of the AGC family, PKA and PKB/AKT (see Yang et al., Nature Struct. Biology 9:940-944, 2002, which is incorporated by reference in its entirety). A ribbon diagram shown in FIG. 1 illustrates the conserved core of the structure, a small N-terminal lobe (residues 377-461) and a large C-terminal lobe (residues 466-696), connected by a flexible polypeptide linker (residues 462-465, NGGD), which functions as a hinge. The N-terminal lobe included a five-stranded β-sheet (β1-β5) and two alpha helices (αB and αC), and the C-terminal lobe was mostly helical having eight α-helices (αD-αK) and four β-strands (β6-β9).
The ATP-binding pocket was occupied by staurosporine and was located near the hinge segment at the interface of the two lobes. The nucleotide-binding loop between β strands 1 and 2 (residues 386-394), also termed the glycine-rich loop (LGxGxxGxV) (SEQ ID NO:4), shows considerable structural variability in many protein kinases (see Bossemeyer et al., Trends Biochem. Sci. 19:201-205, 1994, which is incorporated by reference in its entirety). In the PKCθ structure, the glycine-rich loop adopted a closed, fixed conformation as a result of staurosporine binding. The key catalytic residues that are invariant in all kinases were present in the PKCθ structure. These residues preserved intramolecular interactions observed in other active kinase structures, in accordance with structural criteria used to define catalytically active kinase conformations (see Huse and Kuriyan, Cell 109:257-282, 2002, which is incorporated by reference in its entirety).
As in most Ser/Thr kinase structures reflecting active enzymes (Johnson et al., Cell 85:149-158, 1996, which is incorporated by reference in its entirety), the activation segment of the C-lobe (residues 526-540) was well ordered, adopted an extended conformation and had a phosphorylated Thr at position 538. The phosphorylation of Thr538 indicated autophosphorylation (as opposed to phosphorylation catalyzed by another enzyme) of the activation segment, as the kinase domain is expressed in E. coli. Some of the ionic interactions, in particular between phosphothreonine 538 and positively charged Arg 503 and Lys 527, were similar to the equivalent interactions in PKA and PKB, whereas there were clear differences between those involving helix αC (see below).
The C-terminal hydrophobic motif (HM, sequence: FxxFS*, where * represents phosphorylation of the serine side chain), is a conserved feature across the AGC family. In the PKCθ structure, Ser695 was phosphorylated and was adjacent to the hydrophobic groove of the N-lobe, in a location similar to the FXXF-binding pocket in PKA and PKB. The HM motif is also autophosphorylated by the PKCθ kinase domain. It has been suggested that phosphorylation of the HM serine stabilizes the active conformation of AGC kinases by promoting tight intramolecular association between the HM and the N-lobe (see Yang et al., Nature Struct. Biology 9:940-944, 2002). Interactions between the characteristic aromatic residues, phosphoserine 695 and the hydrophobic groove of the N-lobe were preserved, indicating that phosphoserine 695 plays a similar role in PKCθ as in PKA and PKB.
Staurosporine is a natural product protein kinase inhibitor that has low nanomolar potency against PKC isoforms, but only micromolar potency against other protein kinases such as casein kinase 1 (CK1), casein kinase 2 (CK2), mitogen-activated protein kinase (MAPK) and CSK (see Meggio et al., Eur. J. Biochem. 234:317-22, 1995, which is incorporated by reference in its entirety). Because of this selectivity, staurosporine has been used as a pharmacophore model for targeting the catalytic site of kinases for rational drug design.
Staurosporine occupied the adenosine-binding pocket of PKCθ. The inhibitor formed three hydrogen bonds with the backbone of the enzyme and made extensive van der Waals contacts within a deep hydrophobic cleft between the N- and C-lobes. See FIG. 2, which shows van der Waals contacts between staurosporine and PKCθ in the ATP-binding site. The hydrogen-bonding motif involved interactions between the lactam ring of staurosporine and backbone atoms of Glu459 and Leu461, and between the glycosidic ring and carbonyl oxygen of Asp508. The majority of nonpolar interactions came from the glycine-rich loop residues (Leu386, Gly387, Gly389, Val394) and the remaining interactions involved four residues from the N-terminal lobe (Ala407, Lys409, Met458, and Tyr460) and nine residues from the C-terminal lobe (Leu461, Gly464, Leu466, Leu511, Ala521, Val422, Asn509, Ala521, and Asp522).
There were significant differences in staurosporine-PKCθ contacts when compared to structures of the PKA and CDK2 kinases bound to staurosporine. First, staurosporine made only three hydrogen bonds with PKCθ as opposed to the four potential hydrogen bond contacts in both PKA and CDK2. A significant difference lay in the glycine-rich loop. Specifically, in contrast to PKA and CDK2, accommodation of staurosporine in PKCθ led to the full closure of the glycine-rich loop. As a result, the backbone and side-chain residues in this region (residues 388-392) moved deeper into the ATP-binding pocket adopting positions that would clash with ATP, thereby making significantly more non-polar contacts with staurosporine. Similar shifts of the equivalent residues have been observed upon staurosporine binding to MK2 (Underwood et al., Structure 11:627-636, 2003, which is incorporated by reference in its entirety).
The activation segment is a highly variable structural element that is critical for regulation and catalytic activity of protein kinases. This region acts as a docking site for activating or inactivating cofactors (see Engh and Bossemeyer, Pharmrcology & Therapeutics 93:99-111, 2002, which is incorporated by reference in its entirety) and provides the P+1 pocket for accommodation of peptide substrates. Like in other Ser/Thr protein kinases, the activation segment of PKCθ (residues 522-543) is located between the invariant DFG and TPD motifs and includes a highly conserved phosphorylation site at Thr538. Indeed, clear electron density for the phosphate group attached to this residue was observed, indicating that Thr538 was phosphorylated autocatalytically during expression in E. coli. Interestingly, the sequence flanking the phosphorylated Thr538 (KTNT*F, where * represents phosphorylation) contains a positively charged residue at position −3, which is compatible with the preferred substrate sequence recognized by PKC subfamily (RXXT*/S*F) (see Nishikawa et al., J. Biol. Chem. 272:952-60, 1997, which is incorporated by reference in its entirety). Unlike the majority of PKC isoforms which lack this basic residue, the presence of Lys535 suggests a possibility for PKCθ to phosphorylate itself on Thr538, and is consistent with the determination the K409W mutant of full-length PKCθ is not phosphorylated at the activation loop and is inactive (see Liu et al., Biochem. J. 361:255-265, 2002, which is incorporated by reference in its entirety). Likewise, the K409W mutant of the catalytic domain of PKCθ was not phosphorylated at the activation loop and was inactive.
Structural results have suggested that the key role for the phosphate group in the activation segment is to compensate for a cluster of positively charged residues that point towards the activation segment. In PKCθ, the phosphorylated Thr538 formed two hydrogen bonds with Arg503 and one hydrogen bond with Lys527. This network of interactions is highly conserved in many protein kinases and plays an important role in activation. Specifically, ionic interactions of the Thr538 phosphate through conserved Arg503 can provide a direct link to the catalytic loop helping stabilize the correct orientation of the catalytic base, Asp504. In addition to the electrostatic interaction with basic residues, the phosphorylated Thr538 was also hydrogen bonded to the side chain oxygen of Thr536. In vitro activity studies of full length PKCθ immunoprecipitated from transfected HEK293 cells demonstrated that the Thr538Glu mutant was 3-fold less active than the wild-type enzyme (see Liu et al., Biochem. J. 361:255-265, 2002). This is consistent with the finding that all three oxygen atoms of the phosphate group are involved in direct ionic interactions with the protein, indicating that the glutamic acid at this position would provide only a partial mimic of the phosphoamino acid. Overall, these ionic contacts can stabilize the conformation of the phosphorylated activation loop, similar to that observed in active states of PKA and PKB.
Within the PKC subfamily, phosphorylation at the activation segment Thr is distinct between PKCθ, PKCκ, and PKCδ. PKCδ, in contrast to both PKCθ and PKCκ, does not require the activation segment Thr for activity. PKCδ presumably utilizes the nearby Glu500 residue to maintain some of the ionic interactions that described above for the phosphorylated PKCθ kinase domain. Interestingly, Glu500 is unique to PKCδ and not seen on other PKC isoforms. Consistent with this and again in contrast to PKCθ, the Thr to Glu acid substitution on PKCδ serves only to enhance the kinase activity in comparison with wild type (see Liu et al., Biochem. J. 361:255-265, 2002), presumably by facilitating the additional ionic interactions with the protein. Unlike PKCθ, the PKCκ activation segment Thr is not capable of autophosphorylation and is reported to be phosphorylated by PDK-1 (see Cenni et al., Biochem. J. 363:537-545, 2002, which is incorporated by reference in its entirety). PDK-1 association with PKCθ has been reported also (see Liu et al., Biochem. J. 361:255-265, 2002). However, the PKCθ kinase domain can autophosphorylate the activation segment Thr.
In addition to distinctions within the PKC novel subfamily, details of interactions involved in structural coupling between the activation loop and helix αC were quite different in PKCθ compared to other AGC kinases, including PKA or PKB. As in other kinases, the αC helix links together the N-lobe, the C-lobe and the active site. See FIG. 1. Glu428, the invariant glutamate residue at the N-terminus of the helix, formed an ion pair with the invariant lysine residue in the catalytic center, Lys409, and made direct contacts with the conserved DFG motif of the activation segment. A K409R mutation eliminated the catalytic activity of PKCθ (see Villalba and Altman, Current Cancer Drug Targets 2:125-137, 2002, which is incorporated by reference in its entirety).
In both PKA and PKB, helix αC provided a basic residue (His87 in PKA and His196 in PKB) to contact the phosphoamino acid. In PKCθ, the structurally equivalent residue is Cys424. Due to this sequence difference, the equivalent ion pair was absent from PKCθ. Instead, a new hydrogen bonding pattern was observed that links the αC helix directly to the activation segment, but did not engage the phosphate group. This pairing scheme involved electrostatic interaction between Glu528 from the N-terminal part of the activation segment and Arg430 from the αC helix. Thus, the structural role of the invariant histidine-phosphothreonine contact to promote the correct lobe orientation in PKA and PKB, can be accomplished in PKCθ by the alternative ion pair involving Glu528 and Arg430.
PKCθ, like other protein kinases, has two additional conserved phosphorylation sites referred to as the turn motif (residues 657-685) and the hydrophobic motif (HM) FxxFS* (residues 691-695). In the PKCθ structure, the region corresponding to the turn motif was completely disordered. There was no clearly defined electron density for residues 650-687. Residues 697-706 were also disordered. Unlike the hydrophobic motif (HM) of PKB, which has a stretch of 17 well-ordered amino acid residues, the HM of PKCθ was considerably shorter (residues 688-696) and showed high B-factor values, indicating disorder in this segment. Together these observations suggested that the turn motif and the HM of PKCθ were inherently flexible, either in this particular crystal form or due to the absence of kinase substrates.
The phosphate group attached at Ser695 of PKCθ had clear electron density and formed two hydrogen bonds with Gln449—one with its side chain atom and another one with its main chain amide nitrogen. The observed hydrogen bonding pattern was consistent with the results of the analysis of PKCθ activity in vitro. Substitution of glutamic acid for serine at this position in full-length PKCθ (i.e., the Ser695Glu mutant) was a satisfactory mimic of the PKCθ HM phosphorylation. Full length PKCθ Ser695Glu had 60% of the catalytic activity of wild type full length PKCθ. (see Liu et al., Biochem. J., 361:255-265, 2002).
There were also extensive hydrophobic contacts between the HM motif and the hydrophobic groove of the N-lobe. These involved the invariant phenylalanine residues (Phe691 and Phe694) and residues from the αB and αC helices and the β5 strand (Lys413, Val416, Leu417, Val422, Met426, Lys429, Thr447, Leu454 and Phe456). Together these interactions can play an important structural role in stabilizing ordered conformations of the αB and αC helices. The equivalent phenylalanine residues in PKA and PKB were shown to be essential for the stability and catalytic activity of these enzymes (see Balendran et al., Curr. Biol. 9:393-404, 1999; and Alessi et al., EMBO J. 15:6541-6551, 1996, each of which is incorporated by reference in its entirety).
The HM phosphorylation of PKCθ was required for optimal enzyme activity, with 5-fold reduction of kinase activity in the full length PKCθ Ser695Ala mutant immunoprecipitated from transfected HEK293 cells (see Liu et al., Biochem. J. 361:255-265, 2002). The PKCθ mutant T538A had completely lost phosphorylation of its hydrophobic motif, indicating that the HM region represents a site of autophosphorylation. See Lang and Cohen, Sci. STKE 108:RE17, 2001; and Yang et al., Molecular Cell 9:1227-1240, 2002, each of which is incorporated by reference in its entirety. By mutation analysis of the kinase domain expressed in E. coli, we have shown that the Ser695Ala catalytic domain mutant has completely lost phosphorylation of the activation segment at Thr538, suggesting that PKCθ autophosphorylation involves both the HM and activation segment phosphorylation as the initial activation mechanism.
The inactive and active conformations of other published AGC kinases, including their phosphorylated and non- or partially-phosphorylated counterparts, displayed different structural features. These differences, in addition to conformational changes seen in the activation segment and in the C-terminal hydrophobic motif, involved the relative disposition of the N- and C-lobes associated with structural disorder or misalignment of the αB and αC helices in the N-lobe. Like PKB and PKA (which were crystallized in their active state), the αB and αC helices, activation segment and HM of PKCθ were well ordered and were aligned with respect to the catalytic site residues. This stands in contrast to the corresponding regions of inactive PKA and PKB, which were characterized by a conformational disorder or structural misalignment.
Moreover, a detailed comparison of PKCθ with two so far reported main conformational states of protein kinases referred to as “open” and “closed” showed that the kinase domain of PKCθ in complex with staurosporine adopted a unique partially closed conformation (see Biondi et al., EMBO J. 21:4219-4228, 2002, which is incorporated by reference in its entirety). Two classification criteria were applied to distinguish between open and closed conformation: opening of the glycine-rich loop (based on distance Ser53-Gly186 in the PKA structure) and positioning of the αC-helix (based on the distance between His87 and phosphorylated Thr197). See Taylor et al., Annu. Rev. Cell. Biol. 8:429-62, 1992, which is incorporated by reference in its entirety. In order to avoid possible complications related with sequence discrepancy at structurally equivalent positions, and hence make these criteria applicable to PKCθ, the distances between the Cα-atoms of corresponding residues were measured instead. The results of this comparison indicated that, expect for the glycine-rich loop, the relative disposition of the lobes in PKCθ showed most similarity to ‘intermediate’ kinase structures: PKA in complex with inhibitors staurosporine or balanol and PDK1 in complex with ATP. Thus, the catalytic domain of PCKθ displayed an ‘intermediate’ conformation along with the full closure of the glycine rich-loop upon staurosporine binding, i.e., a partially closed conformation.







TABLE 2







Structure coordinates for PKCθ


(residues 377-696 of SEQ ID NO: 1)/staurosporine complex


















#
name
res
chain
res #
X
Y
Z
occ
B





















ATOM
1
CB
ILE
A
377
61.260
10.244
−14.257
1.00
43.86


ATOM
2
CG2
ILE
A
377
61.609
9.554
−15.554
1.00
44.55


ATOM
3
CG1
ILE
A
377
61.570
9.315
−13.080
1.00
43.99


ATOM
4
CD1
ILE
A
377
60.966
9.772
−11.760
1.00
43.08


ATOM
5
C
ILE
A
377
63.544
11.244
−14.112
1.00
43.99


ATOM
6
O
ILE
A
377
64.112
10.883
−13.080
1.00
43.10


ATOM
7
N
ILE
A
377
61.751
12.499
−15.245
1.00
43.07


ATOM
8
CA
ILE
A
377
62.055
11.565
−14.122
1.00
43.87


ATOM
9
N
GLU
A
378
64.172
11.377
−15.274
1.00
43.76


ATOM
10
CA
GLU
A
378
65.594
11.119
−15.386
1.00
43.81


ATOM
11
CB
GLU
A
378
65.990
10.928
−16.858
1.00
46.16


ATOM
12
CG
GLU
A
378
65.811
9.502
−17.392
1.00
49.37


ATOM
13
CD
GLU
A
378
64.371
9.163
−17.775
1.00
51.62


ATOM
14
OE1
GLU
A
378
63.490
10.047
−17.676
1.00
52.31


ATOM
15
OE2
GLU
A
378
64.121
8.005
−18.185
1.00
53.49


ATOM
16
C
GLU
A
378
66.372
12.276
−14.759
1.00
41.90


ATOM
17
O
GLU
A
378
67.591
12.205
−14.607
1.00
42.24


ATOM
18
N
ASP
A
379
65.658
13.337
−14.389
1.00
39.92


ATOM
19
CA
ASP
A
379
66.282
14.490
−13.750
1.00
38.76


ATOM
20
CB
ASP
A
379
65.432
15.747
−13.930
1.00
39.52


ATOM
21
CG
ASP
A
379
65.225
16.104
−15.383
1.00
40.80


ATOM
22
OD1
ASP
A
379
66.099
15.764
−16.208
1.00
42.30


ATOM
23
OD2
ASP
A
379
64.195
16.736
−15.698
1.00
41.13


ATOM
24
C
ASP
A
379
66.435
14.206
−12.259
1.00
36.67


ATOM
25
O
ASP
A
379
66.997
15.005
−11.514
1.00
36.14


ATOM
26
N
PHE
A
380
65.927
13.054
−11.838
1.00
34.33


ATOM
27
CA
PHE
A
380
65.990
12.649
−10.443
1.00
32.84


ATOM
28
CB
PHE
A
380
64.579
12.429
−9.885
1.00
31.32


ATOM
29
CG
PHE
A
380
63.740
13.675
−9.801
1.00
30.09


ATOM
30
CD1
PHE
A
380
63.842
14.526
−8.706
1.00
29.54


ATOM
31
CD2
PHE
A
380
62.821
13.978
−10.802
1.00
29.70


ATOM
32
CE1
PHE
A
380
63.039
15.660
−8.605
1.00
29.54


ATOM
33
CE2
PHE
A
380
62.012
15.107
−10.713
1.00
29.34


ATOM
34
CZ
PHE
A
380
62.120
15.952
−9.610
1.00
30.14


ATOM
35
C
PHE
A
380
66.753
11.341
−10.305
1.00
32.62


ATOM
36
O
PHE
A
380
66.767
10.518
−11.220
1.00
31.48


ATOM
37
N
ILE
A
381
67.392
11.165
−9.155
1.00
32.46


ATOM
38
CA
ILE
A
381
68.098
9.932
−8.855
1.00
31.18


ATOM
39
CB
ILE
A
381
69.502
10.179
−8.239
1.00
31.14


ATOM
40
CG2
ILE
A
381
70.088
8.862
−7.738
1.00
29.68


ATOM
41
CG1
ILE
A
381
70.438
10.794
−9.282
1.00
31.75


ATOM
42
CD1
ILE
A
381
71.799
11.184
−8.733
1.00
31.78


ATOM
43
C
ILE
A
381
67.208
9.284
−7.799
1.00
31.29


ATOM
44
O
ILE
A
381
66.887
9.907
−6.784
1.00
31.14


ATOM
45
N
LEU
A
382
66.787
8.051
−8.047
1.00
30.65


ATOM
46
CA
LEU
A
382
65.940
7.347
−7.098
1.00
31.26


ATOM
47
CB
LEU
A
382
64.956
6.435
−7.837
1.00
30.86


ATOM
48
CG
LEU
A
382
64.040
7.140
−8.842
1.00
30.89


ATOM
49
CD1
LEU
A
382
62.943
6.182
−9.275
1.00
31.47


ATOM
50
CD2
LEU
A
382
63.421
8.378
−8.213
1.00
31.32


ATOM
51
C
LEU
A
382
66.830
6.535
−6.172
1.00
31.58


ATOM
52
O
LEU
A
382
67.157
5.382
−6.454
1.00
31.79


ATOM
53
N
HIS
A
383
67.220
7.160
−5.066
1.00
31.52


ATOM
54
CA
HIS
A
383
68.102
6.545
−4.086
1.00
32.64


ATOM
55
CB
HIS
A
383
68.499
7.589
−3.043
1.00
32.11


ATOM
56
CG
HIS
A
383
69.340
8.697
−3.596
1.00
31.41


ATOM
57
CD2
HIS
A
383
69.024
9.963
−3.956
1.00
30.95


ATOM
58
ND1
HIS
A
383
70.683
8.548
−3.866
1.00
32.34


ATOM
59
CE1
HIS
A
383
71.158
9.673
−4.369
1.00
31.11


ATOM
60
NE2
HIS
A
383
70.171
10.547
−4.434
1.00
30.71


ATOM
61
C
HIS
A
383
67.533
5.313
−3.393
1.00
34.22


ATOM
62
O
HIS
A
383
68.239
4.320
−3.207
1.00
34.52


ATOM
63
N
LYS
A
384
66.266
5.373
−3.001
1.00
35.09


ATOM
64
CA
LYS
A
384
65.653
4.235
−2.329
1.00
36.72


ATOM
65
CB
LYS
A
384
66.178
4.120
−0.897
1.00
37.82


ATOM
66
CG
LYS
A
384
65.945
5.359
−0.043
1.00
39.26


ATOM
67
CD
LYS
A
384
66.465
5.158
1.375
1.00
40.56


ATOM
68
CE
LYS
A
384
67.963
4.875
1.390
1.00
41.12


ATOM
69
NZ
LYS
A
384
68.460
4.568
2.761
1.00
41.51


ATOM
70
C
LYS
A
384
64.139
4.302
−2.296
1.00
36.60


ATOM
71
O
LYS
A
384
63.540
5.347
−2.544
1.00
36.73


ATOM
72
N
MET
A
385
63.525
3.170
−1.988
1.00
37.13


ATOM
73
CA
MET
A
385
62.080
3.097
−1.905
1.00
38.73


ATOM
74
CB
MET
A
385
61.592
1.735
−2.380
1.00
40.93


ATOM
75
CG
MET
A
385
60.096
1.656
−2.427
1.00
44.71


ATOM
76
SD
MET
A
385
59.474
−0.006
−2.554
1.00
49.30


ATOM
77
CE
MET
A
385
57.783
0.362
−2.870
1.00
48.67


ATOM
78
C
MET
A
385
61.655
3.310
−0.457
1.00
38.14


ATOM
79
O
MET
A
385
62.022
2.529
0.422
1.00
38.59


ATOM
80
N
LEU
A
386
60.893
4.373
−0.208
1.00
37.50


ATOM
81
CA
LEU
A
386
60.426
4.677
1.143
1.00
36.58


ATOM
82
CB
LEU
A
386
59.989
6.140
1.240
1.00
35.18


ATOM
83
CG
LEU
A
386
61.064
7.205
1.016
1.00
34.48


ATOM
84
CD1
LEU
A
386
60.429
8.595
1.020
1.00
33.98


ATOM
85
CD2
LEU
A
386
62.122
7.097
2.101
1.00
34.59


ATOM
86
C
LEU
A
386
59.268
3.769
1.538
1.00
37.02


ATOM
87
O
LEU
A
386
59.131
3.396
2.703
1.00
36.40


ATOM
88
N
GLY
A
387
58.436
3.419
0.566
1.00
37.86


ATOM
89
CA
GLY
A
387
57.307
2.549
0.843
1.00
40.15


ATOM
90
C
GLY
A
387
56.221
2.648
−0.207
1.00
42.28


ATOM
91
O
GLY
A
387
56.404
3.282
−1.246
1.00
42.47


ATOM
92
N
LYS
A
388
55.085
2.017
0.064
1.00
44.15


ATOM
93
CA
LYS
A
388
53.955
2.041
−0.857
1.00
46.93


ATOM
94
CB
LYS
A
388
53.636
0.623
−1.336
1.00
48.32


ATOM
95
CG
LYS
A
388
53.521
−0.388
−0.215
1.00
50.61


ATOM
96
CD
LYS
A
388
53.366
−1.797
−0.753
1.00
52.47


ATOM
97
CE
LYS
A
388
53.307
−2.813
0.382
1.00
53.23


ATOM
98
NZ
LYS
A
388
53.228
−4.212
−0.129
1.00
53.72


ATOM
99
C
LYS
A
388
52.744
2.651
−0.159
1.00
48.02


ATOM
100
O
LYS
A
388
52.312
2.171
0.891
1.00
47.70


ATOM
101
N
GLY
A
389
52.210
3.723
−0.733
1.00
49.03


ATOM
102
CA
GLY
A
389
51.059
4.372
−0.130
1.00
50.80


ATOM
103
C
GLY
A
389
49.775
4.026
−0.849
1.00
52.03


ATOM
104
O
GLY
A
389
49.770
3.105
−1.675
1.00
51.88


ATOM
105
N
SER
A
390
48.697
4.747
−0.528
1.00
53.06


ATOM
106
CA
SER
A
390
47.383
4.550
−1.163
1.00
53.97


ATOM
107
CB
SER
A
390
46.682
5.903
−1.340
1.00
54.09


ATOM
108
OG
SER
A
390
47.548
6.810
−1.995
1.00
55.74


ATOM
109
C
SER
A
390
47.577
3.868
−2.491
1.00
54.31


ATOM
110
O
SER
A
390
47.163
2.719
−2.676
1.00
54.56


ATOM
111
N
PHE
A
391
48.192
4.586
−3.425
1.00
54.43


ATOM
112
CA
PHE
A
391
48.541
3.992
−4.720
1.00
54.69


ATOM
113
CB
PHE
A
391
47.506
4.274
−5.842
1.00
56.06


ATOM
114
CG
PHE
A
391
46.793
5.613
−5.742
1.00
57.62


ATOM
115
CD1
PHE
A
391
47.502
6.795
−5.798
1.00
58.68


ATOM
116
CD2
PHE
A
391
45.391
5.667
−5.801
1.00
58.30


ATOM
117
CE1
PHE
A
391
46.874
8.022
−5.926
1.00
58.76


ATOM
118
CE2
PHE
A
391
44.730
6.919
−5.934
1.00
59.27


ATOM
119
CZ
PHE
A
391
45.484
8.096
−5.998
1.00
58.75


ATOM
120
C
PHE
A
391
49.926
4.425
−5.163
1.00
53.64


ATOM
121
O
PHE
A
391
50.395
5.511
−4.831
1.00
54.01


ATOM
122
N
GLY
A
392
50.598
3.542
−5.888
1.00
51.85


ATOM
123
CA
GLY
A
392
51.936
3.838
−6.377
1.00
49.32


ATOM
124
C
GLY
A
392
52.965
3.758
−5.276
1.00
47.28


ATOM
125
O
GLY
A
392
52.628
3.815
−4.097
1.00
47.40


ATOM
126
N
LYS
A
393
54.222
3.624
−5.671
1.00
44.62


ATOM
127
CA
LYS
A
393
55.312
3.526
−4.724
1.00
40.96


ATOM
128
CB
LYS
A
393
56.394
2.601
−5.284
1.00
43.12


ATOM
129
CG
LYS
A
393
55.882
1.238
−5.751
1.00
45.23


ATOM
130
CD
LYS
A
393
55.351
0.417
−4.584
1.00
47.97


ATOM
131
CE
LYS
A
393
55.013
−1.016
−4.985
1.00
49.61


ATOM
132
NZ
LYS
A
393
54.591
−1.834
−3.799
1.00
51.11


ATOM
133
C
LYS
A
393
55.902
4.906
−4.447
1.00
37.45


ATOM
134
O
LYS
A
393
55.762
5.818
−5.258
1.00
35.26


ATOM
135
N
VAL
A
394
56.552
5.062
−3.295
1.00
34.25


ATOM
136
CA
VAL
A
394
57.168
6.338
−2.941
1.00
31.12


ATOM
137
CB
VAL
A
394
56.580
6.905
−1.638
1.00
31.15


ATOM
138
CG1
VAL
A
394
57.249
8.238
−1.304
1.00
29.93


ATOM
139
CG2
VAL
A
394
55.072
7.079
−1.793
1.00
28.47


ATOM
140
C
VAL
A
394
58.674
6.163
−2.791
1.00
30.07


ATOM
141
O
VAL
A
394
59.137
5.286
−2.061
1.00
28.52


ATOM
142
N
PHE
A
395
59.429
7.013
−3.483
1.00
28.61


ATOM
143
CA
PHE
A
395
60.887
6.949
−3.477
1.00
28.02


ATOM
144
CB
PHE
A
395
61.406
6.719
−4.902
1.00
28.94


ATOM
145
CG
PHE
A
395
60.877
5.477
−5.561
1.00
30.73


ATOM
146
CD1
PHE
A
395
61.538
4.262
−5.416
1.00
31.92


ATOM
147
CD2
PHE
A
395
59.718
5.520
−6.329
1.00
31.34


ATOM
148
CE1
PHE
A
395
61.055
3.106
−6.030
1.00
32.16


ATOM
149
CE2
PHE
A
395
59.224
4.368
−6.947
1.00
33.06


ATOM
150
CZ
PHE
A
395
59.894
3.159
−6.796
1.00
32.73


ATOM
151
C
PHE
A
395
61.557
8.213
−2.956
1.00
26.85


ATOM
152
O
PHE
A
395
61.037
9.315
−3.117
1.00
27.10


ATOM
153
N
LEU
A
396
62.716
8.041
−2.329
1.00
26.25


ATOM
154
CA
LEU
A
396
63.498
9.175
−1.863
1.00
26.29


ATOM
155
CB
LEU
A
396
64.519
8.733
−0.811
1.00
26.87


ATOM
156
CG
LEU
A
396
65.623
9.721
−0.408
1.00
28.36


ATOM
157
CD1
LEU
A
396
65.023
11.005
0.163
1.00
27.25


ATOM
158
CD2
LEU
A
396
66.534
9.047
0.614
1.00
27.56


ATOM
159
C
LEU
A
396
64.201
9.574
−3.155
1.00
25.98


ATOM
160
O
LEU
A
396
64.960
8.784
−3.718
1.00
26.49


ATOM
161
N
ALA
A
397
63.932
10.781
−3.639
1.00
25.33


ATOM
162
CA
ALA
A
397
64.514
11.229
−4.896
1.00
24.12


ATOM
163
CB
ALA
A
397
63.404
11.402
−5.926
1.00
24.69


ATOM
164
C
ALA
A
397
65.333
12.509
−4.812
1.00
24.45


ATOM
165
O
ALA
A
397
64.947
13.475
−4.155
1.00
24.98


ATOM
166
N
GLU
A
398
66.468
12.514
−5.497
1.00
24.62


ATOM
167
CA
GLU
A
398
67.328
13.687
−5.517
1.00
24.57


ATOM
168
CB
GLU
A
398
68.790
13.298
−5.274
1.00
23.76


ATOM
169
CG
GLU
A
398
69.764
14.461
−5.405
1.00
21.43


ATOM
170
CD
GLU
A
398
71.221
14.023
−5.362
1.00
21.44


ATOM
171
OE1
GLU
A
398
72.105
14.899
−5.477
1.00
20.70


ATOM
172
OE2
GLU
A
398
71.482
12.810
−5.216
1.00
21.19


ATOM
173
C
GLU
A
398
67.222
14.355
−6.877
1.00
25.47


ATOM
174
O
GLU
A
398
67.334
13.693
−7.904
1.00
24.24


ATOM
175
N
PHE
A
399
66.987
15.663
−6.879
1.00
26.98


ATOM
176
CA
PHE
A
399
66.924
16.411
−8.126
1.00
29.36


ATOM
177
CB
PHE
A
399
66.165
17.722
−7.924
1.00
29.46


ATOM
178
CG
PHE
A
399
66.030
18.544
−9.173
1.00
31.11


ATOM
179
CD1
PHE
A
399
65.419
18.018
−10.308
1.00
32.01


ATOM
180
CD2
PHE
A
399
66.517
19.850
−9.217
1.00
31.95


ATOM
181
CE1
PHE
A
399
65.293
18.783
−11.472
1.00
31.30


ATOM
182
CE2
PHE
A
399
66.397
20.621
−10.373
1.00
31.86


ATOM
183
CZ
PHE
A
399
65.783
20.084
−11.501
1.00
31.32


ATOM
184
C
PHE
A
399
68.391
16.687
−8.470
1.00
30.10


ATOM
185
O
PHE
A
399
69.009
17.589
−7.906
1.00
30.57


ATOM
186
N
LYS
A
400
68.931
15.891
−9.389
1.00
31.06


ATOM
187
CA
LYS
A
400
70.331
15.975
−9.821
1.00
32.56


ATOM
188
CB
LYS
A
400
70.492
15.305
−11.185
1.00
32.12


ATOM
189
CG
LYS
A
400
70.230
13.817
−11.161
1.00
34.00


ATOM
190
CD
LYS
A
400
70.351
13.218
−12.547
1.00
35.11


ATOM
191
CE
LYS
A
400
69.953
11.757
−12.533
1.00
36.02


ATOM
192
NZ
LYS
A
400
70.083
11.134
−13.877
1.00
37.94


ATOM
193
C
LYS
A
400
71.026
17.332
−9.865
1.00
32.31


ATOM
194
O
LYS
A
400
72.119
17.484
−9.323
1.00
32.07


ATOM
195
N
LYS
A
401
70.407
18.313
−10.508
1.00
33.24


ATOM
196
CA
LYS
A
401
71.015
19.635
−10.632
1.00
34.37


ATOM
197
CB
LYS
A
401
70.251
20.462
−11.670
1.00
36.78


ATOM
198
CG
LYS
A
401
70.386
19.945
−13.093
1.00
39.95


ATOM
199
CD
LYS
A
401
69.539
20.762
−14.060
1.00
43.32


ATOM
200
CE
LYS
A
401
69.940
22.236
−14.049
1.00
46.49


ATOM
201
NZ
LYS
A
401
69.064
23.065
−14.933
1.00
48.15


ATOM
202
C
LYS
A
401
71.149
20.457
−9.357
1.00
33.98


ATOM
203
O
LYS
A
401
71.881
21.441
−9.338
1.00
34.73


ATOM
204
N
THR
A
402
70.467
20.066
−8.286
1.00
33.84


ATOM
205
CA
THR
A
402
70.538
20.852
−7.059
1.00
32.57


ATOM
206
CB
THR
A
402
69.211
21.582
−6.820
1.00
33.23


ATOM
207
OG1
THR
A
402
68.154
20.619
−6.741
1.00
33.77


ATOM
208
CG2
THR
A
402
68.922
22.551
−7.963
1.00
32.46


ATOM
209
C
THR
A
402
70.880
20.091
−5.786
1.00
31.39


ATOM
210
O
THR
A
402
71.137
20.705
−4.750
1.00
31.77


ATOM
211
N
ASN
A
403
70.891
18.764
−5.858
1.00
30.02


ATOM
212
CA
ASN
A
403
71.172
17.936
−4.686
1.00
29.78


ATOM
213
CB
ASN
A
403
72.445
18.394
−3.958
1.00
30.04


ATOM
214
CG
ASN
A
403
73.701
18.198
−4.782
1.00
27.58


ATOM
215
OD1
ASN
A
403
73.985
17.098
−5.251
1.00
28.41


ATOM
216
ND2
ASN
A
403
74.465
19.268
−4.952
1.00
26.62


ATOM
217
C
ASN
A
403
70.003
17.992
−3.706
1.00
30.21


ATOM
218
O
ASN
A
403
70.106
17.506
−2.583
1.00
31.06


ATOM
219
N
GLN
A
404
68.894
18.592
−4.126
1.00
30.39


ATOM
220
CA
GLN
A
404
67.718
18.676
−3.264
1.00
30.79


ATOM
221
CB
GLN
A
404
66.780
19.787
−3.731
1.00
32.65


ATOM
222
CG
GLN
A
404
67.366
21.179
−3.633
1.00
37.04


ATOM
223
CD
GLN
A
404
66.400
22.236
−4.126
1.00
40.26


ATOM
224
OE1
GLN
A
404
65.333
22.440
−3.540
1.00
42.34


ATOM
225
NE2
GLN
A
404
66.761
22.907
−5.215
1.00
41.47


ATOM
226
C
GLN
A
404
66.977
17.345
−3.290
1.00
28.62


ATOM
227
O
GLN
A
404
66.777
16.754
−4.354
1.00
26.94


ATOM
228
N
PHE
A
405
66.576
16.871
−2.115
1.00
26.69


ATOM
229
CA
PHE
A
405
65.869
15.604
−2.028
1.00
25.08


ATOM
230
CB
PHE
A
405
66.432
14.756
−0.880
1.00
24.63


ATOM
231
CG
PHE
A
405
67.770
14.140
−1.190
1.00
24.41


ATOM
232
CD1
PHE
A
405
68.865
14.944
−1.500
1.00
23.39


ATOM
233
CD2
PHE
A
405
67.926
12.757
−1.217
1.00
24.12


ATOM
234
CE1
PHE
A
405
70.095
14.379
−1.837
1.00
21.96


ATOM
235
CE2
PHE
A
405
69.155
12.182
−1.553
1.00
24.18


ATOM
236
CZ
PHE
A
405
70.241
12.997
−1.865
1.00
22.68


ATOM
237
C
PHE
A
405
64.373
15.807
−1.870
1.00
24.33


ATOM
238
O
PHE
A
405
63.920
16.790
−1.287
1.00
23.85


ATOM
239
N
PHE
A
406
63.614
14.860
−2.409
1.00
23.00


ATOM
240
CA
PHE
A
406
62.163
14.904
−2.376
1.00
22.04


ATOM
241
CB
PHE
A
406
61.625
15.456
−3.702
1.00
20.90


ATOM
242
CG
PHE
A
406
62.029
16.872
−3.986
1.00
22.14


ATOM
243
CD1
PHE
A
406
61.329
17.936
−3.422
1.00
22.86


ATOM
244
CD2
PHE
A
406
63.124
17.146
−4.805
1.00
23.26


ATOM
245
CE1
PHE
A
406
61.713
19.256
−3.667
1.00
24.28


ATOM
246
CE2
PHE
A
406
63.521
18.463
−5.061
1.00
23.64


ATOM
247
CZ
PHE
A
406
62.818
19.518
−4.491
1.00
24.60


ATOM
248
C
PHE
A
406
61.628
13.495
−2.190
1.00
22.49


ATOM
249
O
PHE
A
406
62.372
12.513
−2.261
1.00
22.54


ATOM
250
N
ALA
A
407
60.330
13.402
−1.945
1.00
22.28


ATOM
251
CA
ALA
A
407
59.688
12.108
−1.811
1.00
22.69


ATOM
252
CB
ALA
A
407
58.898
12.032
−0.531
1.00
21.54


ATOM
253
C
ALA
A
407
58.761
12.059
−3.014
1.00
23.26


ATOM
254
O
ALA
A
407
57.851
12.883
−3.132
1.00
22.90


ATOM
255
N
ILE
A
408
59.006
11.115
−3.918
1.00
23.59


ATOM
256
CA
ILE
A
408
58.180
11.002
−5.112
1.00
24.60


ATOM
257
CB
ILE
A
408
59.047
10.971
−6.400
1.00
25.27


ATOM
258
CG2
ILE
A
408
58.157
10.771
−7.626
1.00
25.90


ATOM
259
CG1
ILE
A
408
59.831
12.278
−6.532
1.00
25.85


ATOM
260
CD1
ILE
A
408
60.663
12.382
−7.789
1.00
25.12


ATOM
261
C
ILE
A
408
57.290
9.771
−5.100
1.00
25.34


ATOM
262
O
ILE
A
408
57.753
8.650
−4.889
1.00
25.39


ATOM
263
N
LYS
A
409
56.001
10.003
−5.313
1.00
25.71


ATOM
264
CA
LYS
A
409
55.021
8.935
−5.377
1.00
26.54


ATOM
265
CB
LYS
A
409
53.689
9.415
−4.802
1.00
26.41


ATOM
266
CG
LYS
A
409
52.586
8.363
−4.757
1.00
27.51


ATOM
267
CD
LYS
A
409
51.415
8.892
−3.945
1.00
29.29


ATOM
268
CE
LYS
A
409
50.377
7.827
−3.668
1.00
29.58


ATOM
269
NZ
LYS
A
409
49.491
8.208
−2.539
1.00
29.26


ATOM
270
C
LYS
A
409
54.872
8.637
−6.864
1.00
27.38


ATOM
271
O
LYS
A
409
54.531
9.526
−7.644
1.00
27.13


ATOM
272
N
ALA
A
410
55.148
7.399
−7.259
1.00
28.59


ATOM
273
CA
ALA
A
410
55.044
7.014
−8.661
1.00
31.48


ATOM
274
CB
ALA
A
410
56.345
6.367
−9.122
1.00
30.20


ATOM
275
C
ALA
A
410
53.878
6.058
−8.869
1.00
32.81


ATOM
276
O
ALA
A
410
53.694
5.114
−8.101
1.00
32.74


ATOM
277
N
LEU
A
411
53.094
6.315
−9.911
1.00
35.30


ATOM
278
CA
LEU
A
411
51.931
5.491
−10.240
1.00
38.42


ATOM
279
CB
LEU
A
411
50.645
6.283
−9.976
1.00
39.70


ATOM
280
CG
LEU
A
411
50.432
6.781
−8.544
1.00
41.05


ATOM
281
CD1
LEU
A
411
49.441
7.921
−8.485
1.00
41.56


ATOM
282
CD2
LEU
A
411
49.950
5.640
−7.728
1.00
41.63


ATOM
283
C
LEU
A
411
51.968
5.066
−11.710
1.00
39.97


ATOM
284
O
LEU
A
411
52.261
5.877
−12.590
1.00
39.82


ATOM
285
N
LYS
A
412
51.660
3.799
−11.968
1.00
41.51


ATOM
286
CA
LYS
A
412
51.652
3.259
−13.327
1.00
42.58


ATOM
287
CB
LYS
A
412
51.956
1.759
−13.289
1.00
43.71


ATOM
288
CG
LYS
A
412
53.197
1.409
−12.478
1.00
45.79


ATOM
289
CD
LYS
A
412
53.219
−0.060
−12.091
1.00
48.20


ATOM
290
CE
LYS
A
412
53.701
−0.227
−10.650
1.00
49.51


ATOM
291
NZ
LYS
A
412
53.861
−1.657
−10.241
1.00
50.84


ATOM
292
C
LYS
A
412
50.271
3.491
−13.928
1.00
42.91


ATOM
293
O
LYS
A
412
49.303
2.844
−13.531
1.00
43.03


ATOM
294
N
LYS
A
413
50.183
4.419
−14.875
1.00
43.31


ATOM
295
CA
LYS
A
413
48.913
4.738
−15.518
1.00
43.75


ATOM
296
CB
LYS
A
413
49.159
5.491
−16.825
1.00
43.54


ATOM
297
CG
LYS
A
413
49.791
6.846
−16.644
1.00
42.54


ATOM
298
CD
LYS
A
413
50.017
7.520
−17.978
1.00
42.37


ATOM
299
CE
LYS
A
413
50.621
8.894
−17.781
1.00
41.90


ATOM
300
NZ
LYS
A
413
50.949
9.566
−19.064
1.00
41.51


ATOM
301
C
LYS
A
413
48.056
3.512
−15.811
1.00
45.15


ATOM
302
O
LYS
A
413
46.858
3.496
−15.535
1.00
45.34


ATOM
303
N
ASP
A
414
48.684
2.482
−16.365
1.00
46.13


ATOM
304
CA
ASP
A
414
47.997
1.257
−16.738
1.00
47.18


ATOM
305
CB
ASP
A
414
49.008
0.352
−17.463
1.00
49.16


ATOM
306
CG
ASP
A
414
48.491
−1.051
−17.728
1.00
51.39


ATOM
307
OD1
ASP
A
414
47.256
−1.262
−17.799
1.00
52.57


ATOM
308
OD2
ASP
A
414
49.354
−1.949
−17.882
1.00
53.60


ATOM
309
C
ASP
A
414
47.265
0.535
−15.599
1.00
46.66


ATOM
310
O
ASP
A
414
46.148
0.071
−15.800
1.00
46.58


ATOM
311
N
VAL
A
415
47.841
0.426
−14.404
1.00
46.12


ATOM
312
CA
VAL
A
415
47.065
−0.248
−13.367
1.00
45.42


ATOM
313
CB
VAL
A
415
47.974
−0.949
−12.283
1.00
45.49


ATOM
314
CG1
VAL
A
415
49.222
−1.503
−12.951
1.00
45.84


ATOM
315
CG2
VAL
A
415
48.315
−0.013
−11.143
1.00
45.66


ATOM
316
C
VAL
A
415
46.070
0.767
−12.772
1.00
45.01


ATOM
317
O
VAL
A
415
45.032
0.383
−12.229
1.00
44.28


ATOM
318
N
VAL
A
416
46.361
2.061
−12.930
1.00
44.87


ATOM
319
CA
VAL
A
416
45.468
3.123
−12.446
1.00
45.58


ATOM
320
CB
VAL
A
416
46.090
4.538
−12.634
1.00
45.24


ATOM
321
CG1
VAL
A
416
45.017
5.615
−12.459
1.00
44.34


ATOM
322
CG2
VAL
A
416
47.212
4.757
−11.627
1.00
44.33


ATOM
323
C
VAL
A
416
44.139
3.073
−13.209
1.00
46.40


ATOM
324
O
VAL
A
416
43.081
3.355
−12.648
1.00
46.71


ATOM
325
N
LEU
A
417
44.200
2.708
−14.487
1.00
47.08


ATOM
326
CA
LEU
A
417
43.005
2.618
−15.322
1.00
48.24


ATOM
327
CB
LEU
A
417
43.392
2.711
−16.798
1.00
47.71


ATOM
328
CG
LEU
A
417
43.745
4.126
−17.252
1.00
47.40


ATOM
329
CD1
LEU
A
417
44.464
4.107
−18.590
1.00
47.15


ATOM
330
CD2
LEU
A
417
42.465
4.930
−17.323
1.00
47.60


ATOM
331
C
LEU
A
417
42.244
1.326
−15.062
1.00
49.31


ATOM
332
O
LEU
A
417
41.016
1.323
−14.976
1.00
49.26


ATOM
333
N
MET
A
418
42.983
0.230
−14.934
1.00
50.92


ATOM
334
CA
MET
A
418
42.392
−1.072
−14.663
1.00
52.54


ATOM
335
CB
MET
A
418
43.484
−2.134
−14.631
1.00
54.34


ATOM
336
CG
MET
A
418
44.252
−2.259
−15.928
1.00
57.38


ATOM
337
SD
MET
A
418
43.284
−3.092
−17.188
1.00
61.64


ATOM
338
CE
MET
A
418
43.493
−4.785
−16.658
1.00
59.07


ATOM
339
C
MET
A
418
41.696
−1.006
−13.312
1.00
52.57


ATOM
340
O
MET
A
418
40.559
−1.448
−13.163
1.00
53.07


ATOM
341
N
ASP
A
419
42.391
−0.452
−12.325
1.00
52.90


ATOM
342
CA
ASP
A
419
41.822
−0.316
−10.995
1.00
52.76


ATOM
343
CB
ASP
A
419
42.925
−0.167
−9.944
1.00
53.36


ATOM
344
CG
ASP
A
419
43.754
−1.429
−9.791
1.00
53.84


ATOM
345
OD1
ASP
A
419
43.196
−2.533
−9.993
1.00
54.31


ATOM
346
OD2
ASP
A
419
44.953
−1.318
−9.455
1.00
53.61


ATOM
347
C
ASP
A
419
40.905
0.899
−10.980
1.00
52.53


ATOM
348
O
ASP
A
419
40.459
1.344
−9.925
1.00
53.11


ATOM
349
N
ASP
A
420
40.635
1.424
−12.172
1.00
51.98


ATOM
350
CA
ASP
A
420
39.754
2.572
−12.361
1.00
51.41


ATOM
351
CB
ASP
A
420
38.320
2.086
−12.526
1.00
54.26


ATOM
352
CG
ASP
A
420
37.841
1.287
−11.328
1.00
56.90


ATOM
353
OD1
ASP
A
420
38.247
0.112
−11.193
1.00
58.86


ATOM
354
OD2
ASP
A
420
37.072
1.841
−10.511
1.00
58.56


ATOM
355
C
ASP
A
420
39.788
3.606
−11.238
1.00
49.91


ATOM
356
O
ASP
A
420
38.741
4.043
−10.767
1.00
49.93


ATOM
357
N
ASP
A
421
40.980
4.000
−10.805
1.00
47.41


ATOM
358
CA
ASP
A
421
41.094
4.989
−9.739
1.00
45.18


ATOM
359
CB
ASP
A
421
41.960
4.457
−8.597
1.00
47.03


ATOM
360
CG
ASP
A
421
41.406
3.189
−7.990
1.00
49.15


ATOM
361
OD1
ASP
A
421
40.170
3.002
−8.033
1.00
50.60


ATOM
362
OD2
ASP
A
421
42.206
2.387
−7.457
1.00
50.37


ATOM
363
C
ASP
A
421
41.695
6.289
−10.262
1.00
42.40


ATOM
364
O
ASP
A
421
42.558
6.890
−9.619
1.00
40.21


ATOM
365
N
VAL
A
422
41.233
6.718
−11.431
1.00
39.96


ATOM
366
CA
VAL
A
422
41.732
7.939
−12.031
1.00
38.12


ATOM
367
CB
VAL
A
422
41.202
8.101
−13.457
1.00
37.55


ATOM
368
CG1
VAL
A
422
41.864
9.298
−14.130
1.00
37.26


ATOM
369
CG2
VAL
A
422
41.496
6.835
−14.242
1.00
38.40


ATOM
370
C
VAL
A
422
41.347
9.152
−11.187
1.00
37.11


ATOM
371
O
VAL
A
422
42.165
10.048
−10.999
1.00
35.39


ATOM
372
N
GLU
A
423
40.120
9.169
−10.666
1.00
36.67


ATOM
373
CA
GLU
A
423
39.670
10.286
−9.851
1.00
37.19


ATOM
374
CB
GLU
A
423
38.143
10.304
−9.704
1.00
38.72


ATOM
375
CG
GLU
A
423
37.574
11.298
−8.658
1.00
41.68


ATOM
376
CD
GLU
A
423
37.811
12.782
−8.980
1.00
43.48


ATOM
377
OE1
GLU
A
423
38.308
13.099
−10.088
1.00
44.39


ATOM
378
OE2
GLU
A
423
37.484
13.635
−8.117
1.00
45.44


ATOM
379
C
GLU
A
423
40.332
10.247
−8.481
1.00
36.30


ATOM
380
O
GLU
A
423
40.593
11.288
−7.875
1.00
36.39


ATOM
381
N
CYS
A
424
40.616
9.040
−7.984
1.00
35.01


ATOM
382
CA
CYS
A
424
41.300
8.930
−6.693
1.00
34.82


ATOM
383
CB
CYS
A
424
41.450
7.479
−6.278
1.00
37.40


ATOM
384
SG
CYS
A
424
39.877
6.714
−5.865
1.00
44.91


ATOM
385
C
CYS
A
424
42.673
9.629
−6.777
1.00
32.90


ATOM
386
O
CYS
A
424
43.164
10.191
−5.783
1.00
32.59


ATOM
387
N
THR
A
425
43.288
9.620
−7.960
1.00
30.54


ATOM
388
CA
THR
A
425
44.590
10.245
−8.093
1.00
28.60


ATOM
389
CB
THR
A
425
45.380
9.784
−9.353
1.00
28.67


ATOM
390
OG1
THR
A
425
44.775
10.308
−10.541
1.00
31.16


ATOM
391
CG2
THR
A
425
45.423
8.255
−9.441
1.00
27.55


ATOM
392
C
THR
A
425
44.418
11.754
−8.134
1.00
27.85


ATOM
393
O
THR
A
425
45.292
12.495
−7.664
1.00
26.55


ATOM
394
N
MET
A
426
43.302
12.211
−8.704
1.00
25.75


ATOM
395
CA
MET
A
426
43.018
13.638
−8.795
1.00
24.60


ATOM
396
CB
MET
A
426
41.820
13.897
−9.713
1.00
26.29


ATOM
397
CG
MET
A
426
42.020
13.470
−11.155
1.00
28.79


ATOM
398
SD
MET
A
426
43.495
14.210
−11.862
1.00
34.81


ATOM
399
CE
MET
A
426
42.926
15.904
−12.146
1.00
31.22


ATOM
400
C
MET
A
426
42.706
14.149
−7.397
1.00
22.77


ATOM
401
O
MET
A
426
43.038
15.280
−7.047
1.00
21.12


ATOM
402
N
VAL
A
427
42.046
13.313
−6.601
1.00
21.76


ATOM
403
CA
VAL
A
427
41.708
13.685
−5.233
1.00
21.87


ATOM
404
CB
VAL
A
427
40.968
12.541
−4.502
1.00
22.25


ATOM
405
CG1
VAL
A
427
40.756
12.905
−3.033
1.00
23.11


ATOM
406
CG2
VAL
A
427
39.630
12.274
−5.177
1.00
23.45


ATOM
407
C
VAL
A
427
42.987
14.005
−4.460
1.00
21.82


ATOM
408
O
VAL
A
427
43.105
15.071
−3.853
1.00
21.18


ATOM
409
N
GLU
A
428
43.949
13.084
−4.494
1.00
21.50


ATOM
410
CA
GLU
A
428
45.200
13.281
−3.774
1.00
22.20


ATOM
411
CB
GLU
A
428
46.124
12.067
−3.928
1.00
23.46


ATOM
412
CG
GLU
A
428
47.468
12.240
−3.222
1.00
27.57


ATOM
413
CD
GLU
A
428
48.115
10.918
−2.828
1.00
30.32


ATOM
414
OE1
GLU
A
428
48.100
9.980
−3.653
1.00
31.35


ATOM
415
OE2
GLU
A
428
48.646
10.826
−1.692
1.00
30.95


ATOM
416
C
GLU
A
428
45.918
14.538
−4.228
1.00
20.60


ATOM
417
O
GLU
A
428
46.416
15.301
−3.404
1.00
19.26


ATOM
418
N
LYS
A
429
45.969
14.749
−5.538
1.00
20.00


ATOM
419
CA
LYS
A
429
46.615
15.930
−6.088
1.00
19.74


ATOM
420
CB
LYS
A
429
46.485
15.956
−7.615
1.00
21.81


ATOM
421
CG
LYS
A
429
47.074
17.217
−8.231
1.00
24.06


ATOM
422
CD
LYS
A
429
46.877
17.277
−9.729
1.00
27.54


ATOM
423
CE
LYS
A
429
47.223
18.668
−10.246
1.00
30.32


ATOM
424
NZ
LYS
A
429
46.948
18.808
−11.703
1.00
34.56


ATOM
425
C
LYS
A
429
45.957
17.182
−5.522
1.00
19.15


ATOM
426
O
LYS
A
429
46.630
18.140
−5.148
1.00
17.60


ATOM
427
N
ARG
A
430
44.629
17.153
−5.465
1.00
18.16


ATOM
428
CA
ARG
A
430
43.836
18.267
−4.975
1.00
17.28


ATOM
429
CB
ARG
A
430
42.358
17.971
−5.204
1.00
17.62


ATOM
430
CG
ARG
A
430
41.596
19.071
−5.879
1.00
19.56


ATOM
431
CD
ARG
A
430
40.733
18.521
−6.993
1.00
17.79


ATOM
432
NE
ARG
A
430
39.892
17.416
−6.547
1.00
20.15


ATOM
433
CZ
ARG
A
430
39.412
16.482
−7.364
1.00
20.47


ATOM
434
NH1
ARG
A
430
39.691
16.530
−8.664
1.00
17.10


ATOM
435
NH2
ARG
A
430
38.672
15.491
−6.882
1.00
20.20


ATOM
436
C
ARG
A
430
44.078
18.559
−3.502
1.00
17.55


ATOM
437
O
ARG
A
430
44.282
19.709
−3.117
1.00
16.62


ATOM
438
N
VAL
A
431
44.048
17.523
−2.674
1.00
17.10


ATOM
439
CA
VAL
A
431
44.260
17.708
−1.246
1.00
17.74


ATOM
440
CB
VAL
A
431
43.914
16.419
−0.460
1.00
18.52


ATOM
441
CG1
VAL
A
431
44.130
16.644
1.041
1.00
17.16


ATOM
442
CG2
VAL
A
431
42.458
16.031
−0.735
1.00
16.07


ATOM
443
C
VAL
A
431
45.705
18.133
−0.975
1.00
18.19


ATOM
444
O
VAL
A
431
45.954
18.964
−0.102
1.00
18.13


ATOM
445
N
LEU
A
432
46.654
17.591
−1.731
1.00
18.42


ATOM
446
CA
LEU
A
432
48.044
17.988
−1.541
1.00
20.18


ATOM
447
CB
LEU
A
432
48.989
17.147
−2.411
1.00
20.15


ATOM
448
CG
LEU
A
432
49.309
15.711
−1.987
1.00
22.09


ATOM
449
CD1
LEU
A
432
50.062
15.017
−3.110
1.00
20.23


ATOM
450
CD2
LEU
A
432
50.145
15.707
−0.705
1.00
23.08


ATOM
451
C
LEU
A
432
48.204
19.475
−1.889
1.00
21.02


ATOM
452
O
LEU
A
432
48.988
20.179
−1.254
1.00
20.53


ATOM
453
N
SER
A
433
47.468
19.953
−2.894
1.00
20.67


ATOM
454
CA
SER
A
433
47.550
21.365
−3.276
1.00
22.20


ATOM
455
CB
SER
A
433
46.764
21.640
−4.561
1.00
22.20


ATOM
456
OG
SER
A
433
47.364
20.970
−5.654
1.00
27.08


ATOM
457
C
SER
A
433
46.978
22.208
−2.153
1.00
21.39


ATOM
458
O
SER
A
433
47.506
23.259
−1.812
1.00
21.27


ATOM
459
N
LEU
A
434
45.886
21.731
−1.578
1.00
21.50


ATOM
460
CA
LEU
A
434
45.240
22.423
−0.477
1.00
21.43


ATOM
461
CB
LEU
A
434
43.971
21.671
−0.092
1.00
20.13


ATOM
462
CG
LEU
A
434
43.222
22.168
1.139
1.00
21.96


ATOM
463
CD1
LEU
A
434
42.574
23.518
0.855
1.00
23.04


ATOM
464
CD2
LEU
A
434
42.172
21.141
1.510
1.00
22.32


ATOM
465
C
LEU
A
434
46.181
22.497
0.735
1.00
21.31


ATOM
466
O
LEU
A
434
46.363
23.560
1.327
1.00
20.57


ATOM
467
N
ALA
A
435
46.776
21.356
1.080
1.00
22.20


ATOM
468
CA
ALA
A
435
47.676
21.230
2.230
1.00
22.69


ATOM
469
CB
ALA
A
435
48.274
19.827
2.260
1.00
21.45


ATOM
470
C
ALA
A
435
48.797
22.262
2.324
1.00
23.79


ATOM
471
O
ALA
A
435
49.353
22.475
3.401
1.00
22.59


ATOM
472
N
TRP
A
436
49.132
22.894
1.206
1.00
25.03


ATOM
473
CA
TRP
A
436
50.197
23.891
1.201
1.00
27.02


ATOM
474
CB
TRP
A
436
50.252
24.568
−0.170
1.00
29.65


ATOM
475
CG
TRP
A
436
51.421
25.479
−0.326
1.00
31.45


ATOM
476
CD2
TRP
A
436
52.753
25.103
−0.696
1.00
32.03


ATOM
477
CE2
TRP
A
436
53.538
26.276
−0.677
1.00
33.34


ATOM
478
CE3
TRP
A
436
53.359
23.887
−1.042
1.00
32.87


ATOM
479
CD1
TRP
A
436
51.448
26.825
−0.105
1.00
32.63


ATOM
480
NE1
TRP
A
436
52.717
27.312
−0.313
1.00
33.25


ATOM
481
CZ2
TRP
A
436
54.906
26.270
−0.990
1.00
33.88


ATOM
482
CZ3
TRP
A
436
54.718
23.880
−1.353
1.00
33.29


ATOM
483
CH2
TRP
A
436
55.474
25.065
−1.324
1.00
33.66


ATOM
484
C
TRP
A
436
49.926
24.933
2.287
1.00
28.06


ATOM
485
O
TRP
A
436
50.838
25.464
2.914
1.00
27.33


ATOM
486
N
GLU
A
437
48.636
25.183
2.487
1.00
28.61


ATOM
487
CA
GLU
A
437
48.121
26.148
3.456
1.00
28.70


ATOM
488
CB
GLU
A
437
46.592
26.302
3.266
1.00
31.22


ATOM
489
CG
GLU
A
437
45.989
27.658
3.775
1.00
35.77


ATOM
490
CD
GLU
A
437
44.491
27.732
3.537
1.00
37.44


ATOM
491
OE1
GLU
A
437
44.046
27.334
2.436
1.00
39.80


ATOM
492
OE2
GLU
A
437
43.763
28.248
4.417
1.00
37.82


ATOM
493
C
GLU
A
437
48.405
25.786
4.939
1.00
28.26


ATOM
494
O
GLU
A
437
48.539
26.677
5.779
1.00
28.42


ATOM
495
N
HIS
A
438
48.513
24.491
5.241
1.00
24.97


ATOM
496
CA
HIS
A
438
48.705
24.035
6.620
1.00
22.59


ATOM
497
CB
HIS
A
438
47.622
22.997
6.936
1.00
21.19


ATOM
498
CG
HIS
A
438
47.344
22.830
8.396
1.00
22.04


ATOM
499
CD2
HIS
A
438
47.803
21.925
9.292
1.00
21.85


ATOM
500
ND1
HIS
A
438
46.501
23.668
9.092
1.00
21.68


ATOM
501
CE1
HIS
A
438
46.452
23.288
10.356
1.00
22.37


ATOM
502
NE2
HIS
A
438
47.235
22.234
10.504
1.00
22.90


ATOM
503
C
HIS
A
438
50.088
23.446
6.974
1.00
20.75


ATOM
504
O
HIS
A
438
50.654
22.673
6.211
1.00
20.81


ATOM
505
N
PRO
A
439
50.618
23.755
8.173
1.00
19.49


ATOM
506
CD
PRO
A
439
50.092
24.654
9.216
1.00
18.88


ATOM
507
CA
PRO
A
439
51.932
23.230
8.562
1.00
18.82


ATOM
508
CB
PRO
A
439
52.304
24.092
9.764
1.00
18.84


ATOM
509
CG
PRO
A
439
50.976
24.326
10.406
1.00
18.97


ATOM
510
C
PRO
A
439
51.989
21.744
8.903
1.00
18.39


ATOM
511
O
PRO
A
439
53.053
21.132
8.817
1.00
18.26


ATOM
512
N
PHE
A
440
50.859
21.152
9.268
1.00
18.66


ATOM
513
CA
PHE
A
440
50.865
19.746
9.654
1.00
19.86


ATOM
514
CB
PHE
A
440
50.127
19.582
10.986
1.00
18.03


ATOM
515
CG
PHE
A
440
50.652
20.491
12.083
1.00
20.56


ATOM
516
CD1
PHE
A
440
52.022
20.665
12.266
1.00
18.71


ATOM
517
CD2
PHE
A
440
49.773
21.192
12.911
1.00
19.36


ATOM
518
CE1
PHE
A
440
52.510
21.528
13.251
1.00
20.45


ATOM
519
CE2
PHE
A
440
50.249
22.055
13.897
1.00
19.82


ATOM
520
CZ
PHE
A
440
51.624
22.226
14.069
1.00
19.84


ATOM
521
C
PHE
A
440
50.349
18.758
8.607
1.00
20.28


ATOM
522
O
PHE
A
440
49.966
17.634
8.928
1.00
20.61


ATOM
523
N
LEU
A
441
50.347
19.185
7.351
1.00
20.58


ATOM
524
CA
LEU
A
441
49.942
18.323
6.248
1.00
20.81


ATOM
525
CB
LEU
A
441
48.695
18.875
5.549
1.00
20.65


ATOM
526
CG
LEU
A
441
47.390
18.957
6.349
1.00
20.89


ATOM
527
CD1
LEU
A
441
46.274
19.442
5.436
1.00
21.21


ATOM
528
CD2
LEU
A
441
47.043
17.591
6.917
1.00
20.09


ATOM
529
C
LEU
A
441
51.116
18.304
5.268
1.00
21.61


ATOM
530
O
LEU
A
441
51.814
19.306
5.110
1.00
20.26


ATOM
531
N
THR
A
442
51.333
17.166
4.618
1.00
22.42


ATOM
532
CA
THR
A
442
52.424
17.037
3.658
1.00
23.21


ATOM
533
CB
THR
A
442
52.572
15.569
3.184
1.00
23.90


ATOM
534
OG1
THR
A
442
52.751
14.715
4.322
1.00
23.44


ATOM
535
CG2
THR
A
442
53.775
15.421
2.243
1.00
24.18


ATOM
536
C
THR
A
442
52.167
17.929
2.440
1.00
24.13


ATOM
537
O
THR
A
442
51.056
17.950
1.904
1.00
22.62


ATOM
538
N
HIS
A
443
53.201
18.656
2.014
1.00
24.40


ATOM
539
CA
HIS
A
443
53.112
19.550
0.862
1.00
25.25


ATOM
540
CB
HIS
A
443
53.894
20.849
1.100
1.00
24.58


ATOM
541
CG
HIS
A
443
53.492
21.584
2.336
1.00
23.06


ATOM
542
CD2
HIS
A
443
54.158
22.492
3.085
1.00
22.44


ATOM
543
ND1
HIS
A
443
52.254
21.436
2.924
1.00
23.95


ATOM
544
CE1
HIS
A
443
52.175
22.219
3.984
1.00
19.84


ATOM
545
NE2
HIS
A
443
53.316
22.871
4.104
1.00
23.13


ATOM
546
C
HIS
A
443
53.665
18.905
−0.403
1.00
26.11


ATOM
547
O
HIS
A
443
54.524
18.024
−0.355
1.00
26.41


ATOM
548
N
MET
A
444
53.173
19.381
−1.537
1.00
27.13


ATOM
549
CA
MET
A
444
53.588
18.891
−2.841
1.00
28.71


ATOM
550
CB
MET
A
444
52.365
18.343
−3.581
1.00
30.60


ATOM
551
CG
MET
A
444
52.556
18.113
−5.061
1.00
33.85


ATOM
552
SD
MET
A
444
51.032
17.490
−5.794
1.00
40.55


ATOM
553
CE
MET
A
444
50.022
18.963
−5.807
1.00
36.09


ATOM
554
C
MET
A
444
54.188
20.067
−3.602
1.00
28.39


ATOM
555
O
MET
A
444
53.653
21.171
−3.553
1.00
27.44


ATOM
556
N
PHE
A
445
55.300
19.845
−4.293
1.00
29.18


ATOM
557
CA
PHE
A
445
55.925
20.927
−5.038
1.00
30.58


ATOM
558
CB
PHE
A
445
57.444
20.813
−4.976
1.00
30.22


ATOM
559
CG
PHE
A
445
58.000
21.087
−3.619
1.00
30.81


ATOM
560
CD1
PHE
A
445
58.476
20.054
−2.824
1.00
30.80


ATOM
561
CD2
PHE
A
445
58.001
22.381
−3.112
1.00
30.89


ATOM
562
CE1
PHE
A
445
58.943
20.311
−1.535
1.00
31.29


ATOM
563
CE2
PHE
A
445
58.463
22.647
−1.832
1.00
29.72


ATOM
564
CZ
PHE
A
445
58.935
21.613
−1.040
1.00
30.69


ATOM
565
C
PHE
A
445
55.456
20.952
−6.473
1.00
31.46


ATOM
566
O
PHE
A
445
55.149
22.008
−7.022
1.00
31.13


ATOM
567
N
CYS
A
446
55.398
19.786
−7.090
1.00
32.42


ATOM
568
CA
CYS
A
446
54.929
19.731
−8.452
1.00
34.41


ATOM
569
CB
CYS
A
446
56.019
20.154
−9.439
1.00
35.65


ATOM
570
SG
CYS
A
446
57.272
18.924
−9.707
1.00
41.67


ATOM
571
C
CYS
A
446
54.454
18.341
−8.771
1.00
34.80


ATOM
572
O
CYS
A
446
54.503
17.428
−7.947
1.00
33.47


ATOM
573
N
THR
A
447
53.997
18.192
−9.996
1.00
36.01


ATOM
574
CA
THR
A
447
53.470
16.941
−10.453
1.00
38.05


ATOM
575
CB
THR
A
447
51.946
16.917
−10.142
1.00
39.14


ATOM
576
OG1
THR
A
447
51.537
15.592
−9.798
1.00
42.34


ATOM
577
CG2
THR
A
447
51.150
17.403
−11.304
1.00
38.52


ATOM
578
C
THR
A
447
53.808
16.903
−11.944
1.00
38.40


ATOM
579
O
THR
A
447
53.855
17.942
−12.607
1.00
38.77


ATOM
580
N
PHE
A
448
54.106
15.718
−12.456
1.00
38.89


ATOM
581
CA
PHE
A
448
54.465
15.584
−13.857
1.00
40.43


ATOM
582
CB
PHE
A
448
55.930
15.981
−14.068
1.00
40.34


ATOM
583
CG
PHE
A
448
56.924
14.978
−13.535
1.00
40.76


ATOM
584
CD1
PHE
A
448
57.360
13.917
−14.328
1.00
40.15


ATOM
585
CD2
PHE
A
448
57.441
15.105
−12.247
1.00
40.30


ATOM
586
CE1
PHE
A
448
58.303
13.002
−13.848
1.00
41.09


ATOM
587
CE2
PHE
A
448
58.385
14.194
−11.756
1.00
40.11


ATOM
588
CZ
PHE
A
448
58.816
13.141
−12.558
1.00
40.32


ATOM
589
C
PHE
A
448
54.253
14.154
−14.294
1.00
41.70


ATOM
590
O
PHE
A
448
54.101
13.260
−13.460
1.00
40.26


ATOM
591
N
GLN
A
449
54.234
13.934
−15.601
1.00
43.78


ATOM
592
CA
GLN
A
449
54.044
12.592
−16.087
1.00
46.58


ATOM
593
CB
GLN
A
449
52.582
12.370
−16.501
1.00
47.16


ATOM
594
CG
GLN
A
449
52.154
13.037
−17.798
1.00
48.14


ATOM
595
CD
GLN
A
449
50.640
13.049
−17.958
1.00
48.93


ATOM
596
OE1
GLN
A
449
49.989
11.999
−17.922
1.00
49.32


ATOM
597
NE2
GLN
A
449
50.072
14.240
−18.128
1.00
48.57


ATOM
598
C
GLN
A
449
54.958
12.193
−17.224
1.00
48.47


ATOM
599
O
GLN
A
449
55.549
13.022
−17.928
1.00
48.22


ATOM
600
N
THR
A
450
55.088
10.882
−17.340
1.00
50.57


ATOM
601
CA
THR
A
450
55.850
10.233
−18.381
1.00
52.90


ATOM
602
CB
THR
A
450
56.772
9.121
−17.794
1.00
53.12


ATOM
603
OG1
THR
A
450
58.074
9.666
−17.552
1.00
54.78


ATOM
604
CG2
THR
A
450
56.895
7.922
−18.733
1.00
54.96


ATOM
605
C
THR
A
450
54.705
9.628
−19.174
1.00
53.95


ATOM
606
O
THR
A
450
53.539
9.886
−18.877
1.00
54.26


ATOM
607
N
LYS
A
451
55.027
8.820
−20.168
1.00
55.42


ATOM
608
CA
LYS
A
451
54.014
8.198
−20.988
1.00
55.88


ATOM
609
CB
LYS
A
451
54.584
7.997
−22.389
1.00
56.85


ATOM
610
CG
LYS
A
451
53.552
7.738
−23.457
1.00
58.03


ATOM
611
CD
LYS
A
451
54.136
7.970
−24.841
1.00
59.25


ATOM
612
CE
LYS
A
451
54.516
9.434
−25.044
1.00
59.59


ATOM
613
NZ
LYS
A
451
55.019
9.688
−26.424
1.00
60.34


ATOM
614
C
LYS
A
451
53.534
6.873
−20.399
1.00
55.47


ATOM
615
O
LYS
A
451
52.796
6.140
−21.047
1.00
56.36


ATOM
616
N
GLU
A
452
53.937
6.567
−19.167
1.00
54.71


ATOM
617
CA
GLU
A
452
53.526
5.314
−18.535
1.00
53.39


ATOM
618
CB
GLU
A
452
54.588
4.240
−18.786
1.00
55.47


ATOM
619
CG
GLU
A
452
55.039
4.142
−20.235
1.00
58.58


ATOM
620
CD
GLU
A
452
56.351
3.397
−20.391
1.00
60.72


ATOM
621
OE1
GLU
A
452
56.913
3.413
−21.509
1.00
62.08


ATOM
622
OE2
GLU
A
452
56.822
2.796
−19.399
1.00
61.41


ATOM
623
C
GLU
A
452
53.302
5.460
−17.029
1.00
51.25


ATOM
624
O
GLU
A
452
52.755
4.561
−16.387
1.00
50.98


ATOM
625
N
ASN
A
453
53.723
6.590
−16.467
1.00
48.56


ATOM
626
CA
ASN
A
453
53.570
6.815
−15.034
1.00
45.89


ATOM
627
CB
ASN
A
453
54.876
6.481
−14.307
1.00
46.62


ATOM
628
CG
ASN
A
453
55.248
5.019
−14.413
1.00
47.71


ATOM
629
OD1
ASN
A
453
55.677
4.548
−15.466
1.00
48.67


ATOM
630
ND2
ASN
A
453
55.077
4.287
−13.317
1.00
48.16


ATOM
631
C
ASN
A
453
53.152
8.224
−14.632
1.00
43.39


ATOM
632
O
ASN
A
453
53.283
9.179
−15.401
1.00
42.73


ATOM
633
N
LEU
A
454
52.645
8.323
−13.406
1.00
40.18


ATOM
634
CA
LEU
A
454
52.225
9.586
−12.808
1.00
37.46


ATOM
635
CB
LEU
A
454
50.777
9.504
−12.312
1.00
38.03


ATOM
636
CG
LEU
A
454
49.648
9.391
−13.337
1.00
39.23


ATOM
637
CD1
LEU
A
454
48.310
9.311
−12.603
1.00
40.02


ATOM
638
CD2
LEU
A
454
49.671
10.588
−14.270
1.00
39.29


ATOM
639
C
LEU
A
454
53.157
9.812
−11.617
1.00
34.99


ATOM
640
O
LEU
A
454
53.469
8.875
−10.876
1.00
33.99


ATOM
641
N
PHE
A
455
53.595
11.049
−11.424
1.00
32.51


ATOM
642
CA
PHE
A
455
54.508
11.347
−10.331
1.00
30.22


ATOM
643
CB
PHE
A
455
55.914
11.600
−10.884
1.00
29.47


ATOM
644
CG
PHE
A
455
56.529
10.411
−11.572
1.00
31.00


ATOM
645
CD1
PHE
A
455
57.059
9.361
−10.835
1.00
30.85


ATOM
646
CD2
PHE
A
455
56.597
10.350
−12.962
1.00
31.60


ATOM
647
CE1
PHE
A
455
57.650
8.269
−11.471
1.00
31.16


ATOM
648
CE2
PHE
A
455
57.186
9.261
−13.603
1.00
31.10


ATOM
649
CZ
PHE
A
455
57.713
8.221
−12.852
1.00
30.97


ATOM
650
C
PHE
A
455
54.095
12.541
−9.481
1.00
28.80


ATOM
651
O
PHE
A
455
53.752
13.604
−10.001
1.00
28.55


ATOM
652
N
PHE
A
456
54.125
12.352
−8.166
1.00
27.87


ATOM
653
CA
PHE
A
456
53.817
13.426
−7.225
1.00
26.89


ATOM
654
CB
PHE
A
456
52.835
12.977
−6.132
1.00
26.92


ATOM
655
CG
PHE
A
456
51.474
12.567
−6.636
1.00
28.68


ATOM
656
CD1
PHE
A
456
51.305
11.390
−7.365
1.00
29.62


ATOM
657
CD2
PHE
A
456
50.353
13.334
−6.342
1.00
28.90


ATOM
658
CE1
PHE
A
456
50.039
10.986
−7.787
1.00
29.67


ATOM
659
CE2
PHE
A
456
49.077
12.937
−6.763
1.00
29.12


ATOM
660
CZ
PHE
A
456
48.920
11.764
−7.484
1.00
29.10


ATOM
661
C
PHE
A
456
55.151
13.749
−6.549
1.00
26.14


ATOM
662
O
PHE
A
456
55.736
12.885
−5.890
1.00
26.60


ATOM
663
N
VAL
A
457
55.646
14.968
−6.716
1.00
24.61


ATOM
664
CA
VAL
A
457
56.897
15.347
−6.069
1.00
23.87


ATOM
665
CB
VAL
A
457
57.771
16.240
−6.982
1.00
24.28


ATOM
666
CG1
VAL
A
457
59.048
16.648
−6.241
1.00
24.15


ATOM
667
CG2
VAL
A
457
58.127
15.487
−8.262
1.00
22.51


ATOM
668
C
VAL
A
457
56.544
16.106
−4.792
1.00
23.23


ATOM
669
O
VAL
A
457
56.132
17.265
−4.840
1.00
22.81


ATOM
670
N
MET
A
458
56.697
15.433
−3.654
1.00
21.84


ATOM
671
CA
MET
A
458
56.375
16.012
−2.355
1.00
21.93


ATOM
672
CB
MET
A
458
55.502
15.039
−1.563
1.00
22.15


ATOM
673
CG
MET
A
458
54.184
14.683
−2.238
1.00
22.87


ATOM
674
SD
MET
A
458
53.413
13.216
−1.506
1.00
24.96


ATOM
675
CE
MET
A
458
54.231
11.926
−2.446
1.00
23.53


ATOM
676
C
MET
A
458
57.617
16.331
−1.533
1.00
21.95


ATOM
677
O
MET
A
458
58.721
15.889
−1.856
1.00
20.97


ATOM
678
N
GLU
A
459
57.429
17.097
−0.461
1.00
21.81


ATOM
679
CA
GLU
A
459
58.538
17.443
0.417
1.00
22.44


ATOM
680
CB
GLU
A
459
58.098
18.479
1.454
1.00
22.72


ATOM
681
CG
GLU
A
459
57.059
17.985
2.447
1.00
24.00


ATOM
682
CD
GLU
A
459
56.592
19.080
3.388
1.00
25.29


ATOM
683
OE1
GLU
A
459
57.454
19.798
3.930
1.00
27.08


ATOM
684
OE2
GLU
A
459
55.366
19.224
3.597
1.00
25.60


ATOM
685
C
GLU
A
459
59.016
16.170
1.117
1.00
22.69


ATOM
686
O
GLU
A
459
58.225
15.263
1.395
1.00
21.45


ATOM
687
N
TYR
A
460
60.316
16.098
1.373
1.00
22.91


ATOM
688
CA
TYR
A
460
60.908
14.949
2.040
1.00
23.13


ATOM
689
CB
TYR
A
460
62.296
14.683
1.442
1.00
24.36


ATOM
690
CG
TYR
A
460
63.227
13.844
2.291
1.00
24.71


ATOM
691
CD1
TYR
A
460
62.841
12.589
2.762
1.00
24.72


ATOM
692
CE1
TYR
A
460
63.706
11.810
3.529
1.00
25.19


ATOM
693
CD2
TYR
A
460
64.506
14.304
2.608
1.00
25.17


ATOM
694
CE2
TYR
A
460
65.377
13.534
3.374
1.00
26.32


ATOM
695
CZ
TYR
A
460
64.970
12.289
3.831
1.00
25.57


ATOM
696
OH
TYR
A
460
65.827
11.530
4.594
1.00
27.52


ATOM
697
C
TYR
A
460
60.985
15.244
3.540
1.00
23.25


ATOM
698
O
TYR
A
460
61.509
16.274
3.960
1.00
24.64


ATOM
699
N
LEU
A
461
60.437
14.335
4.338
1.00
22.56


ATOM
700
CA
LEU
A
461
60.388
14.468
5.791
1.00
22.00


ATOM
701
CB
LEU
A
461
58.927
14.329
6.236
1.00
21.44


ATOM
702
CG
LEU
A
461
57.988
15.265
5.444
1.00
22.36


ATOM
703
CD1
LEU
A
461
56.519
14.858
5.606
1.00
21.00


ATOM
704
CD2
LEU
A
461
58.206
16.699
5.912
1.00
20.61


ATOM
705
C
LEU
A
461
61.262
13.356
6.370
1.00
22.47


ATOM
706
O
LEU
A
461
60.836
12.207
6.452
1.00
21.94


ATOM
707
N
ASN
A
462
62.481
13.708
6.774
1.00
23.06


ATOM
708
CA
ASN
A
462
63.441
12.721
7.268
1.00
24.58


ATOM
709
CB
ASN
A
462
64.869
13.287
7.219
1.00
23.70


ATOM
710
CG
ASN
A
462
65.091
14.430
8.196
1.00
24.22


ATOM
711
OD1
ASN
A
462
64.504
14.471
9.282
1.00
24.87


ATOM
712
ND2
ASN
A
462
65.966
15.355
7.823
1.00
25.13


ATOM
713
C
ASN
A
462
63.228
12.083
8.631
1.00
25.66


ATOM
714
O
ASN
A
462
64.039
11.259
9.052
1.00
26.27


ATOM
715
N
GLY
A
463
62.150
12.436
9.317
1.00
26.85


ATOM
716
CA
GLY
A
463
61.909
11.857
10.626
1.00
28.07


ATOM
717
C
GLY
A
463
61.325
10.459
10.597
1.00
29.05


ATOM
718
O
GLY
A
463
61.368
9.751
11.603
1.00
31.65


ATOM
719
N
GLY
A
464
60.783
10.053
9.454
1.00
29.15


ATOM
720
CA
GLY
A
464
60.180
8.733
9.353
1.00
29.45


ATOM
721
C
GLY
A
464
58.743
8.751
9.865
1.00
29.34


ATOM
722
O
GLY
A
464
58.273
9.776
10.371
1.00
29.57


ATOM
723
N
ASP
A
465
58.040
7.628
9.746
1.00
26.76


ATOM
724
CA
ASP
A
465
56.657
7.557
10.199
1.00
25.67


ATOM
725
CB
ASP
A
465
55.867
6.585
9.317
1.00
25.97


ATOM
726
CG
ASP
A
465
56.383
5.164
9.409
1.00
26.64


ATOM
727
OD1
ASP
A
465
55.795
4.368
10.172
1.00
25.67


ATOM
728
OD2
ASP
A
465
57.382
4.848
8.725
1.00
27.99


ATOM
729
C
ASP
A
465
56.553
7.145
11.667
1.00
24.77


ATOM
730
O
ASP
A
465
57.456
6.505
12.210
1.00
24.43


ATOM
731
N
LEU
A
466
55.439
7.511
12.298
1.00
23.00


ATOM
732
CA
LEU
A
466
55.211
7.205
13.698
1.00
22.39


ATOM
733
CB
LEU
A
466
53.961
7.932
14.213
1.00
21.37


ATOM
734
CG
LEU
A
466
54.081
9.445
14.429
1.00
20.68


ATOM
735
CD1
LEU
A
466
52.938
9.911
15.318
1.00
19.21


ATOM
736
CD2
LEU
A
466
55.410
9.780
15.093
1.00
19.57


ATOM
737
C
LEU
A
466
55.094
5.719
13.987
1.00
23.24


ATOM
738
O
LEU
A
466
55.513
5.260
15.051
1.00
23.27


ATOM
739
N
MET
A
467
54.514
4.966
13.058
1.00
23.18


ATOM
740
CA
MET
A
467
54.380
3.528
13.257
1.00
24.69


ATOM
741
CB
MET
A
467
53.774
2.861
12.020
1.00
26.98


ATOM
742
CG
MET
A
467
53.645
1.347
12.130
1.00
29.65


ATOM
743
SD
MET
A
467
52.639
0.815
13.534
1.00
34.87


ATOM
744
CE
MET
A
467
51.045
0.659
12.785
1.00
33.52


ATOM
745
C
MET
A
467
55.762
2.942
13.535
1.00
23.90


ATOM
746
O
MET
A
467
55.936
2.150
14.457
1.00
22.82


ATOM
747
N
TYR
A
468
56.742
3.342
12.734
1.00
24.06


ATOM
748
CA
TYR
A
468
58.109
2.867
12.896
1.00
25.72


ATOM
749
CB
TYR
A
468
59.022
3.502
11.844
1.00
27.04


ATOM
750
CG
TYR
A
468
60.472
3.148
12.045
1.00
30.91


ATOM
751
CD1
TYR
A
468
60.943
1.869
11.749
1.00
33.62


ATOM
752
CE1
TYR
A
468
62.271
1.518
11.986
1.00
34.74


ATOM
753
CD2
TYR
A
468
61.368
4.073
12.582
1.00
32.99


ATOM
754
CE2
TYR
A
468
62.697
3.733
12.821
1.00
34.74


ATOM
755
CZ
TYR
A
468
63.138
2.454
12.520
1.00
35.55


ATOM
756
OH
TYR
A
468
64.451
2.116
12.755
1.00
39.66


ATOM
757
C
TYR
A
468
58.651
3.205
14.290
1.00
25.58


ATOM
758
O
TYR
A
468
59.226
2.355
14.971
1.00
24.84


ATOM
759
N
HIS
A
469
58.464
4.454
14.705
1.00
23.87


ATOM
760
CA
HIS
A
469
58.937
4.898
16.007
1.00
24.51


ATOM
761
CB
HIS
A
469
58.727
6.404
16.147
1.00
24.84


ATOM
762
CG
HIS
A
469
59.557
7.208
15.196
1.00
27.55


ATOM
763
CD2
HIS
A
469
59.209
8.066
14.208
1.00
28.42


ATOM
764
ND1
HIS
A
469
60.934
7.152
15.184
1.00
28.86


ATOM
765
CE1
HIS
A
469
61.399
7.940
14.231
1.00
29.62


ATOM
766
NE2
HIS
A
469
60.373
8.506
13.623
1.00
28.82


ATOM
767
C
HIS
A
469
58.270
4.151
17.158
1.00
24.11


ATOM
768
O
HIS
A
469
58.929
3.812
18.138
1.00
22.55


ATOM
769
N
ILE
A
470
56.970
3.894
17.042
1.00
23.67


ATOM
770
CA
ILE
A
470
56.254
3.174
18.088
1.00
25.07


ATOM
771
CB
ILE
A
470
54.715
3.204
17.850
1.00
25.63


ATOM
772
CG2
ILE
A
470
54.034
2.050
18.569
1.00
24.30


ATOM
773
CG1
ILE
A
470
54.143
4.546
18.332
1.00
25.19


ATOM
774
CD1
ILE
A
470
54.371
4.822
19.804
1.00
27.82


ATOM
775
C
ILE
A
470
56.737
1.729
18.161
1.00
25.82


ATOM
776
O
ILE
A
470
56.762
1.137
19.234
1.00
25.55


ATOM
777
N
GLN
A
471
57.127
1.167
17.022
1.00
26.72


ATOM
778
CA
GLN
A
471
57.609
−0.204
16.997
1.00
28.66


ATOM
779
CB
GLN
A
471
57.748
−0.713
15.559
1.00
30.40


ATOM
780
CG
GLN
A
471
56.436
−0.843
14.818
1.00
33.10


ATOM
781
CD
GLN
A
471
56.588
−1.562
13.492
1.00
36.30


ATOM
782
OE1
GLN
A
471
57.463
−1.230
12.685
1.00
37.77


ATOM
783
NE2
GLN
A
471
55.731
−2.549
13.254
1.00
36.53


ATOM
784
C
GLN
A
471
58.956
−0.320
17.702
1.00
29.39


ATOM
785
O
GLN
A
471
59.188
−1.266
18.450
1.00
29.90


ATOM
786
N
SER
A
472
59.840
0.645
17.470
1.00
28.10


ATOM
787
CA
SER
A
472
61.149
0.609
18.092
1.00
29.00


ATOM
788
CB
SER
A
472
62.157
1.394
17.250
1.00
29.93


ATOM
789
OG
SER
A
472
61.823
2.766
17.198
1.00
33.77


ATOM
790
C
SER
A
472
61.150
1.133
19.527
1.00
28.13


ATOM
791
O
SER
A
472
61.954
0.684
20.337
1.00
28.92


ATOM
792
N
CYS
A
473
60.252
2.068
19.841
1.00
26.87


ATOM
793
CA
CYS
A
473
60.164
2.653
21.185
1.00
27.39


ATOM
794
CB
CYS
A
473
59.800
4.139
21.092
1.00
28.88


ATOM
795
SG
CYS
A
473
61.012
5.194
20.268
1.00
38.25


ATOM
796
C
CYS
A
473
59.135
1.964
22.083
1.00
26.23


ATOM
797
O
CYS
A
473
59.119
2.182
23.298
1.00
25.29


ATOM
798
N
HIS
A
474
58.284
1.149
21.462
1.00
25.07


ATOM
799
CA
HIS
A
474
57.202
0.408
22.109
1.00
23.85


ATOM
800
CB
HIS
A
474
57.670
−0.285
23.393
1.00
25.37


ATOM
801
CG
HIS
A
474
58.661
−1.384
23.167
1.00
28.20


ATOM
802
CD2
HIS
A
474
59.471
−1.659
22.116
1.00
29.17


ATOM
803
ND1
HIS
A
474
58.944
−2.335
24.124
1.00
29.29


ATOM
804
CE1
HIS
A
474
59.886
−3.145
23.676
1.00
28.53


ATOM
805
NE2
HIS
A
474
60.224
−2.757
22.460
1.00
30.08


ATOM
806
C
HIS
A
474
56.005
1.311
22.411
1.00
23.60


ATOM
807
O
HIS
A
474
54.859
0.920
22.193
1.00
22.42


ATOM
808
N
LYS
A
475
56.270
2.511
22.921
1.00
22.82


ATOM
809
CA
LYS
A
475
55.207
3.473
23.222
1.00
22.22


ATOM
810
CB
LYS
A
475
54.330
2.990
24.382
1.00
24.73


ATOM
811
CG
LYS
A
475
55.067
2.756
25.690
1.00
26.81


ATOM
812
CD
LYS
A
475
54.155
2.053
26.683
1.00
29.39


ATOM
813
CE
LYS
A
475
54.953
1.362
27.788
1.00
31.24


ATOM
814
NZ
LYS
A
475
54.107
0.400
28.559
1.00
33.84


ATOM
815
C
LYS
A
475
55.793
4.831
23.556
1.00
21.06


ATOM
816
O
LYS
A
475
56.987
4.946
23.839
1.00
20.31


ATOM
817
N
PHE
A
476
54.953
5.861
23.503
1.00
19.63


ATOM
818
CA
PHE
A
476
55.391
7.219
23.803
1.00
19.64


ATOM
819
CB
PHE
A
476
54.822
8.233
22.793
1.00
19.65


ATOM
820
CG
PHE
A
476
55.298
8.044
21.381
1.00
19.76


ATOM
821
CD1
PHE
A
476
56.570
7.542
21.114
1.00
20.06


ATOM
822
CD2
PHE
A
476
54.481
8.414
20.313
1.00
19.20


ATOM
823
CE1
PHE
A
476
57.024
7.410
19.800
1.00
19.83


ATOM
824
CE2
PHE
A
476
54.921
8.288
18.997
1.00
19.06


ATOM
825
CZ
PHE
A
476
56.194
7.785
18.738
1.00
19.95


ATOM
826
C
PHE
A
476
54.912
7.652
25.178
1.00
20.01


ATOM
827
O
PHE
A
476
53.826
7.269
25.620
1.00
18.73


ATOM
828
N
ASP
A
477
55.722
8.467
25.843
1.00
20.43


ATOM
829
CA
ASP
A
477
55.347
9.002
27.144
1.00
21.85


ATOM
830
CB
ASP
A
477
56.498
9.806
27.746
1.00
24.67


ATOM
831
CG
ASP
A
477
56.078
10.573
28.971
1.00
29.03


ATOM
832
OD1
ASP
A
477
55.865
9.931
30.030
1.00
29.58


ATOM
833
OD2
ASP
A
477
55.943
11.817
28.872
1.00
31.01


ATOM
834
C
ASP
A
477
54.161
9.933
26.882
1.00
21.49


ATOM
835
O
ASP
A
477
53.996
10.438
25.767
1.00
19.17


ATOM
836
N
LEU
A
478
53.355
10.183
27.908
1.00
21.46


ATOM
837
CA
LEU
A
478
52.173
11.024
27.745
1.00
22.04


ATOM
838
CB
LEU
A
478
51.420
11.149
29.073
1.00
22.92


ATOM
839
CG
LEU
A
478
50.177
12.045
28.987
1.00
24.53


ATOM
840
CD1
LEU
A
478
49.227
11.490
27.935
1.00
26.73


ATOM
841
CD2
LEU
A
478
49.476
12.123
30.324
1.00
24.26


ATOM
842
C
LEU
A
478
52.413
12.415
27.159
1.00
21.48


ATOM
843
O
LEU
A
478
51.616
12.890
26.353
1.00
20.19


ATOM
844
N
SER
A
479
53.493
13.074
27.560
1.00
20.76


ATOM
845
CA
SER
A
479
53.778
14.412
27.044
1.00
22.81


ATOM
846
CB
SER
A
479
54.967
15.034
27.782
1.00
23.09


ATOM
847
OG
SER
A
479
54.631
15.275
29.138
1.00
27.61


ATOM
848
C
SER
A
479
54.065
14.407
25.545
1.00
22.31


ATOM
849
O
SER
A
479
53.588
15.276
24.813
1.00
22.28


ATOM
850
N
ARG
A
480
54.848
13.431
25.097
1.00
21.15


ATOM
851
CA
ARG
A
480
55.195
13.317
23.688
1.00
21.07


ATOM
852
CB
ARG
A
480
56.271
12.246
23.487
1.00
20.82


ATOM
853
CG
ARG
A
480
56.680
12.063
22.033
1.00
22.55


ATOM
854
CD
ARG
A
480
57.711
10.960
21.887
1.00
24.81


ATOM
855
NE
ARG
A
480
59.013
11.342
22.433
1.00
25.59


ATOM
856
CZ
ARG
A
480
59.883
12.130
21.810
1.00
27.11


ATOM
857
NH1
ARG
A
480
59.590
12.623
20.614
1.00
27.35


ATOM
858
NH2
ARG
A
480
61.049
12.421
22.380
1.00
26.65


ATOM
859
C
ARG
A
480
53.960
12.974
22.853
1.00
20.49


ATOM
860
O
ARG
A
480
53.716
13.593
21.813
1.00
20.34


ATOM
861
N
ALA
A
481
53.186
11.993
23.316
1.00
19.22


ATOM
862
CA
ALA
A
481
51.969
11.563
22.626
1.00
18.63


ATOM
863
CB
ALA
A
481
51.355
10.365
23.336
1.00
17.26


ATOM
864
C
ALA
A
481
50.953
12.699
22.558
1.00
18.28


ATOM
865
O
ALA
A
481
50.258
12.855
21.552
1.00
16.31


ATOM
866
N
THR
A
482
50.868
13.477
23.636
1.00
17.94


ATOM
867
CA
THR
A
482
49.950
14.615
23.715
1.00
16.84


ATOM
868
CB
THR
A
482
49.979
15.269
25.113
1.00
17.81


ATOM
869
OG1
THR
A
482
49.461
14.354
26.086
1.00
19.26


ATOM
870
CG2
THR
A
482
49.147
16.536
25.127
1.00
18.16


ATOM
871
C
THR
A
482
50.323
15.672
22.682
1.00
16.38


ATOM
872
O
THR
A
482
49.451
16.247
22.029
1.00
17.51


ATOM
873
N
PHE
A
483
51.620
15.929
22.538
1.00
15.89


ATOM
874
CA
PHE
A
483
52.103
16.913
21.573
1.00
16.51


ATOM
875
CB
PHE
A
483
53.628
17.068
21.685
1.00
17.27


ATOM
876
CG
PHE
A
483
54.207
18.094
20.748
1.00
18.29


ATOM
877
CD1
PHE
A
483
54.138
19.453
21.051
1.00
19.04


ATOM
878
CD2
PHE
A
483
54.794
17.703
19.545
1.00
19.61


ATOM
879
CE1
PHE
A
483
54.643
20.410
20.170
1.00
19.59


ATOM
880
CE2
PHE
A
483
55.303
18.649
18.658
1.00
20.16


ATOM
881
CZ
PHE
A
483
55.226
20.011
18.972
1.00
19.94


ATOM
882
C
PHE
A
483
51.735
16.505
20.138
1.00
16.55


ATOM
883
O
PHE
A
483
51.233
17.325
19.361
1.00
16.37


ATOM
884
N
TYR
A
484
51.983
15.244
19.785
1.00
14.77


ATOM
885
CA
TYR
A
484
51.667
14.768
18.439
1.00
15.27


ATOM
886
CB
TYR
A
484
52.197
13.349
18.198
1.00
15.72


ATOM
887
CG
TYR
A
484
53.707
13.215
18.235
1.00
17.82


ATOM
888
CD1
TYR
A
484
54.533
14.279
17.871
1.00
17.23


ATOM
889
CE1
TYR
A
484
55.917
14.146
17.857
1.00
16.78


ATOM
890
CD2
TYR
A
484
54.311
12.002
18.587
1.00
17.52


ATOM
891
CE2
TYR
A
484
55.704
11.856
18.570
1.00
15.64


ATOM
892
CZ
TYR
A
484
56.496
12.929
18.205
1.00
16.43


ATOM
893
OH
TYR
A
484
57.868
12.792
18.175
1.00
16.03


ATOM
894
C
TYR
A
484
50.167
14.769
18.209
1.00
14.02


ATOM
895
O
TYR
A
484
49.704
15.118
17.130
1.00
13.93


ATOM
896
N
ALA
A
485
49.417
14.368
19.228
1.00
13.39


ATOM
897
CA
ALA
A
485
47.968
14.319
19.140
1.00
14.86


ATOM
898
CB
ALA
A
485
47.385
13.801
20.446
1.00
12.89


ATOM
899
C
ALA
A
485
47.400
15.700
18.833
1.00
15.70


ATOM
900
O
ALA
A
485
46.507
15.843
18.000
1.00
14.51


ATOM
901
N
ALA
A
486
47.928
16.715
19.508
1.00
16.59


ATOM
902
CA
ALA
A
486
47.457
18.081
19.306
1.00
16.76


ATOM
903
CB
ALA
A
486
48.153
19.026
20.283
1.00
17.23


ATOM
904
C
ALA
A
486
47.681
18.549
17.869
1.00
16.08


ATOM
905
O
ALA
A
486
46.789
19.136
17.272
1.00
16.59


ATOM
906
N
GLU
A
487
48.865
18.303
17.316
1.00
14.04


ATOM
907
CA
GLU
A
487
49.136
18.728
15.942
1.00
16.71


ATOM
908
CB
GLU
A
487
50.635
18.609
15.615
1.00
16.19


ATOM
909
CG
GLU
A
487
51.513
19.477
16.525
1.00
18.81


ATOM
910
CD
GLU
A
487
52.973
19.565
16.080
1.00
20.88


ATOM
911
OE1
GLU
A
487
53.489
18.595
15.475
1.00
19.09


ATOM
912
OE2
GLU
A
487
53.615
20.608
16.359
1.00
21.07


ATOM
913
C
GLU
A
487
48.303
17.915
14.950
1.00
15.58


ATOM
914
O
GLU
A
487
47.911
18.410
13.899
1.00
15.41


ATOM
915
N
ILE
A
488
48.026
16.664
15.291
1.00
15.26


ATOM
916
CA
ILE
A
488
47.208
15.841
14.424
1.00
15.55


ATOM
917
CB
ILE
A
488
47.203
14.379
14.891
1.00
13.11


ATOM
918
CG2
ILE
A
488
46.049
13.613
14.225
1.00
15.10


ATOM
919
CG1
ILE
A
488
48.560
13.751
14.565
1.00
14.20


ATOM
920
CD1
ILE
A
488
48.755
12.349
15.125
1.00
17.27


ATOM
921
C
ILE
A
488
45.788
16.410
14.429
1.00
15.04


ATOM
922
O
ILE
A
488
45.134
16.466
13.391
1.00
16.32


ATOM
923
N
ILE
A
489
45.324
16.843
15.597
1.00
13.00


ATOM
924
CA
ILE
A
489
43.995
17.427
15.721
1.00
13.70


ATOM
925
CB
ILE
A
489
43.711
17.892
17.173
1.00
13.58


ATOM
926
CG2
ILE
A
489
42.581
18.929
17.193
1.00
13.47


ATOM
927
CG1
ILE
A
489
43.366
16.681
18.043
1.00
13.70


ATOM
928
CD1
ILE
A
489
43.269
16.992
19.535
1.00
14.08


ATOM
929
C
ILE
A
489
43.846
18.627
14.780
1.00
15.43


ATOM
930
O
ILE
A
489
42.853
18.718
14.049
1.00
14.03


ATOM
931
N
LEU
A
490
44.827
19.535
14.792
1.00
13.69


ATOM
932
CA
LEU
A
490
44.767
20.718
13.937
1.00
16.37


ATOM
933
CB
LEU
A
490
45.920
21.683
14.258
1.00
17.37


ATOM
934
CG
LEU
A
490
45.834
22.352
15.637
1.00
17.35


ATOM
935
CD1
LEU
A
490
47.078
23.223
15.895
1.00
18.38


ATOM
936
CD2
LEU
A
490
44.572
23.197
15.702
1.00
17.12


ATOM
937
C
LEU
A
490
44.789
20.335
12.460
1.00
16.50


ATOM
938
O
LEU
A
490
44.086
20.925
11.652
1.00
16.06


ATOM
939
N
GLY
A
491
45.593
19.336
12.115
1.00
18.00


ATOM
940
CA
GLY
A
491
45.649
18.888
10.737
1.00
17.83


ATOM
941
C
GLY
A
491
44.290
18.366
10.288
1.00
17.31


ATOM
942
O
GLY
A
491
43.831
18.695
9.190
1.00
16.63


ATOM
943
N
LEU
A
492
43.650
17.557
11.134
1.00
16.73


ATOM
944
CA
LEU
A
492
42.336
16.991
10.832
1.00
18.49


ATOM
945
CB
LEU
A
492
41.895
15.981
11.900
1.00
19.00


ATOM
946
CG
LEU
A
492
42.388
14.532
11.900
1.00
23.20


ATOM
947
CD1
LEU
A
492
41.595
13.767
12.971
1.00
23.49


ATOM
948
CD2
LEU
A
492
42.171
13.877
10.530
1.00
23.88


ATOM
949
C
LEU
A
492
41.266
18.048
10.742
1.00
17.70


ATOM
950
O
LEU
A
492
40.418
18.034
9.821
1.00
16.53


ATOM
951
N
GLN
A
493
41.265
18.965
11.706
1.00
16.20


ATOM
952
CA
GLN
A
493
40.261
20.017
11.721
1.00
16.22


ATOM
953
CB
GLN
A
493
40.341
20.884
12.996
1.00
14.50


ATOM
954
CG
GLN
A
493
39.909
20.077
14.252
1.00
16.12


ATOM
955
CD
GLN
A
493
39.912
20.900
15.495
1.00
15.87


ATOM
956
OE1
GLN
A
493
40.673
21.816
15.648
1.00
18.33


ATOM
957
NE2
GLN
A
493
39.033
20.544
16.442
1.00
15.27


ATOM
958
C
GLN
A
493
40.361
20.936
10.523
1.00
15.70


ATOM
959
O
GLN
A
493
39.363
21.445
10.019
1.00
15.96


ATOM
960
N
PHE
A
494
41.597
21.132
10.022
1.00
15.39


ATOM
961
CA
PHE
A
494
41.794
21.954
8.855
1.00
16.44


ATOM
962
CB
PHE
A
494
43.302
22.146
8.556
1.00
15.32


ATOM
963
CG
PHE
A
494
43.541
22.832
7.252
1.00
17.38


ATOM
964
CD1
PHE
A
494
43.305
24.203
7.116
1.00
17.01


ATOM
965
CD2
PHE
A
494
43.981
22.110
6.152
1.00
15.36


ATOM
966
CE1
PHE
A
494
43.517
24.840
5.902
1.00
17.03


ATOM
967
CE2
PHE
A
494
44.197
22.736
4.930
1.00
17.93


ATOM
968
CZ
PHE
A
494
43.968
24.106
4.804
1.00
17.43


ATOM
969
C
PHE
A
494
41.124
21.245
7.694
1.00
16.04


ATOM
970
O
PHE
A
494
40.313
21.844
6.981
1.00
16.17


ATOM
971
N
LEU
A
495
41.433
19.961
7.531
1.00
14.64


ATOM
972
CA
LEU
A
495
40.841
19.165
6.459
1.00
15.79


ATOM
973
CB
LEU
A
495
41.341
17.711
6.515
1.00
15.11


ATOM
974
CG
LEU
A
495
42.802
17.470
6.129
1.00
16.37


ATOM
975
CD1
LEU
A
495
43.151
15.991
6.298
1.00
15.22


ATOM
976
CD2
LEU
A
495
43.028
17.925
4.695
1.00
15.83


ATOM
977
C
LEU
A
495
39.322
19.173
6.519
1.00
14.97


ATOM
978
O
LEU
A
495
38.652
19.327
5.500
1.00
14.55


ATOM
979
N
HIS
A
496
38.780
18.997
7.718
1.00
15.73


ATOM
980
CA
HIS
A
496
37.332
19.002
7.903
1.00
16.47


ATOM
981
CB
HIS
A
496
36.983
18.639
9.347
1.00
16.06


ATOM
982
CG
HIS
A
496
37.336
17.232
9.717
1.00
17.23


ATOM
983
CD2
HIS
A
496
37.791
16.199
8.969
1.00
17.32


ATOM
984
ND1
HIS
A
496
37.232
16.754
11.004
1.00
16.18


ATOM
985
CE1
HIS
A
496
37.609
15.488
11.034
1.00
16.71


ATOM
986
NE2
HIS
A
496
37.954
15.127
9.813
1.00
15.84


ATOM
987
C
HIS
A
496
36.722
20.360
7.572
1.00
16.31


ATOM
988
O
HIS
A
496
35.634
20.433
7.004
1.00
16.29


ATOM
989
N
SER
A
497
37.423
21.438
7.920
1.00
17.23


ATOM
990
CA
SER
A
497
36.898
22.779
7.662
1.00
16.89


ATOM
991
CB
SER
A
497
37.748
23.854
8.361
1.00
16.11


ATOM
992
OG
SER
A
497
38.983
24.063
7.696
1.00
15.31


ATOM
993
C
SER
A
497
36.867
23.034
6.166
1.00
16.85


ATOM
994
O
SER
A
497
36.124
23.884
5.699
1.00
18.00


ATOM
995
N
LYS
A
498
37.672
22.285
5.419
1.00
15.86


ATOM
996
CA
LYS
A
498
37.718
22.424
3.972
1.00
16.00


ATOM
997
CB
LYS
A
498
39.162
22.272
3.474
1.00
15.59


ATOM
998
CG
LYS
A
498
40.095
23.416
3.892
1.00
16.30


ATOM
999
CD
LYS
A
498
39.712
24.745
3.238
1.00
16.10


ATOM
1000
CE
LYS
A
498
40.597
25.893
3.744
1.00
18.48


ATOM
1001
NZ
LYS
A
498
40.415
27.173
2.962
1.00
16.93


ATOM
1002
C
LYS
A
498
36.804
21.412
3.261
1.00
16.12


ATOM
1003
O
LYS
A
498
36.950
21.170
2.062
1.00
16.06


ATOM
1004
N
GLY
A
499
35.870
20.828
4.007
1.00
16.27


ATOM
1005
CA
GLY
A
499
34.936
19.862
3.438
1.00
18.36


ATOM
1006
C
GLY
A
499
35.532
18.508
3.086
1.00
19.34


ATOM
1007
O
GLY
A
499
35.057
17.823
2.172
1.00
19.30


ATOM
1008
N
ILE
A
500
36.565
18.112
3.818
1.00
19.00


ATOM
1009
CA
ILE
A
500
37.236
16.848
3.559
1.00
18.78


ATOM
1010
CB
ILE
A
500
38.721
17.095
3.182
1.00
19.08


ATOM
1011
CG2
ILE
A
500
39.463
15.769
3.009
1.00
18.70


ATOM
1012
CG1
ILE
A
500
38.796
17.921
1.897
1.00
20.51


ATOM
1013
CD1
ILE
A
500
40.157
18.517
1.637
1.00
19.85


ATOM
1014
C
ILE
A
500
37.192
15.891
4.748
1.00
19.58


ATOM
1015
O
ILE
A
500
37.392
16.291
5.896
1.00
19.29


ATOM
1016
N
VAL
A
501
36.901
14.628
4.455
1.00
19.79


ATOM
1017
CA
VAL
A
501
36.886
13.574
5.457
1.00
19.06


ATOM
1018
CB
VAL
A
501
35.579
12.752
5.410
1.00
19.05


ATOM
1019
CG1
VAL
A
501
35.662
11.582
6.397
1.00
19.68


ATOM
1020
CG2
VAL
A
501
34.387
13.645
5.773
1.00
18.08


ATOM
1021
C
VAL
A
501
38.085
12.733
5.017
1.00
19.05


ATOM
1022
O
VAL
A
501
38.126
12.250
3.883
1.00
17.88


ATOM
1023
N
TYR
A
502
39.066
12.597
5.907
1.00
19.22


ATOM
1024
CA
TYR
A
502
40.315
11.887
5.620
1.00
20.24


ATOM
1025
CB
TYR
A
502
41.325
12.184
6.734
1.00
20.54


ATOM
1026
CG
TYR
A
502
42.708
11.634
6.490
1.00
22.30


ATOM
1027
CD1
TYR
A
502
43.403
11.921
5.313
1.00
22.57


ATOM
1028
CE1
TYR
A
502
44.701
11.428
5.103
1.00
22.84


ATOM
1029
CD2
TYR
A
502
43.338
10.844
7.447
1.00
22.27


ATOM
1030
CE2
TYR
A
502
44.630
10.351
7.243
1.00
22.73


ATOM
1031
CZ
TYR
A
502
45.302
10.647
6.074
1.00
21.57


ATOM
1032
OH
TYR
A
502
46.573
10.152
5.885
1.00
21.68


ATOM
1033
C
TYR
A
502
40.161
10.382
5.411
1.00
21.47


ATOM
1034
O
TYR
A
502
40.691
9.829
4.448
1.00
22.30


ATOM
1035
N
ARG
A
503
39.450
9.732
6.326
1.00
22.06


ATOM
1036
CA
ARG
A
503
39.161
8.305
6.251
1.00
23.80


ATOM
1037
CB
ARG
A
503
38.349
8.005
4.991
1.00
23.28


ATOM
1038
CG
ARG
A
503
37.008
8.703
4.975
1.00
22.23


ATOM
1039
CD
ARG
A
503
36.081
8.075
3.975
1.00
17.63


ATOM
1040
NE
ARG
A
503
36.523
8.241
2.591
1.00
15.18


ATOM
1041
CZ
ARG
A
503
35.739
7.973
1.550
1.00
15.46


ATOM
1042
NH1
ARG
A
503
34.502
7.538
1.765
1.00
14.35


ATOM
1043
NH2
ARG
A
503
36.175
8.148
0.307
1.00
12.82


ATOM
1044
C
ARG
A
503
40.310
7.311
6.336
1.00
24.61


ATOM
1045
O
ARG
A
503
40.080
6.097
6.296
1.00
25.89


ATOM
1046
N
ASP
A
504
41.540
7.790
6.441
1.00
24.36


ATOM
1047
CA
ASP
A
504
42.643
6.851
6.548
1.00
24.64


ATOM
1048
CB
ASP
A
504
43.305
6.645
5.182
1.00
26.23


ATOM
1049
CG
ASP
A
504
44.133
5.372
5.130
1.00
28.98


ATOM
1050
OD1
ASP
A
504
43.706
4.359
5.735
1.00
30.02


ATOM
1051
OD2
ASP
A
504
45.198
5.379
4.479
1.00
29.70


ATOM
1052
C
ASP
A
504
43.678
7.267
7.587
1.00
23.66


ATOM
1053
O
ASP
A
504
44.880
7.080
7.388
1.00
23.47


ATOM
1054
N
LEU
A
505
43.205
7.816
8.703
1.00
22.88


ATOM
1055
CA
LEU
A
505
44.102
8.242
9.768
1.00
22.30


ATOM
1056
CB
LEU
A
505
43.376
9.177
10.743
1.00
22.34


ATOM
1057
CG
LEU
A
505
44.238
9.787
11.856
1.00
23.32


ATOM
1058
CD1
LEU
A
505
45.359
10.602
11.232
1.00
23.36


ATOM
1059
CD2
LEU
A
505
43.379
10.667
12.763
1.00
24.16


ATOM
1060
C
LEU
A
505
44.653
7.038
10.521
1.00
21.25


ATOM
1061
O
LEU
A
505
43.911
6.283
11.139
1.00
22.74


ATOM
1062
N
LYS
A
506
45.964
6.858
10.449
1.00
20.30


ATOM
1063
CA
LYS
A
506
46.626
5.756
11.129
1.00
20.81


ATOM
1064
CB
LYS
A
506
46.515
4.480
10.286
1.00
20.22


ATOM
1065
CG
LYS
A
506
47.103
4.593
8.900
1.00
21.40


ATOM
1066
CD
LYS
A
506
46.811
3.341
8.079
1.00
23.11


ATOM
1067
CE
LYS
A
506
47.477
3.423
6.722
1.00
21.39


ATOM
1068
NZ
LYS
A
506
47.106
2.286
5.856
1.00
26.55


ATOM
1069
C
LYS
A
506
48.089
6.139
11.356
1.00
20.61


ATOM
1070
O
LYS
A
506
48.603
7.038
10.688
1.00
20.40


ATOM
1071
N
LEU
A
507
48.748
5.476
12.303
1.00
20.46


ATOM
1072
CA
LEU
A
507
50.152
5.769
12.622
1.00
21.72


ATOM
1073
CB
LEU
A
507
50.694
4.765
13.637
1.00
21.51


ATOM
1074
CG
LEU
A
507
50.214
4.857
15.083
1.00
20.98


ATOM
1075
CD1
LEU
A
507
50.845
3.730
15.870
1.00
23.11


ATOM
1076
CD2
LEU
A
507
50.589
6.204
15.671
1.00
21.75


ATOM
1077
C
LEU
A
507
51.062
5.758
11.405
1.00
21.54


ATOM
1078
O
LEU
A
507
51.983
6.565
11.294
1.00
20.97


ATOM
1079
N
ASP
A
508
50.799
4.816
10.507
1.00
22.57


ATOM
1080
CA
ASP
A
508
51.564
4.650
9.277
1.00
22.87


ATOM
1081
CB
ASP
A
508
50.966
3.518
8.440
1.00
25.88


ATOM
1082
CG
ASP
A
508
50.753
2.250
9.239
1.00
31.04


ATOM
1083
OD1
ASP
A
508
49.997
2.274
10.248
1.00
33.35


ATOM
1084
OD2
ASP
A
508
51.339
1.223
8.848
1.00
32.58


ATOM
1085
C
ASP
A
508
51.558
5.921
8.436
1.00
21.45


ATOM
1086
O
ASP
A
508
52.495
6.170
7.666
1.00
20.81


ATOM
1087
N
ASN
A
509
50.501
6.719
8.576
1.00
19.00


ATOM
1088
CA
ASN
A
509
50.380
7.943
7.798
1.00
19.78


ATOM
1089
CB
ASN
A
509
48.950
8.091
7.266
1.00
19.10


ATOM
1090
CG
ASN
A
509
48.630
7.069
6.197
1.00
20.16


ATOM
1091
OD1
ASN
A
509
49.535
6.518
5.573
1.00
22.44


ATOM
1092
ND2
ASN
A
509
47.348
6.818
5.968
1.00
20.65


ATOM
1093
C
ASN
A
509
50.807
9.225
8.490
1.00
19.25


ATOM
1094
O
ASN
A
509
50.560
10.313
7.974
1.00
19.05


ATOM
1095
N
ILE
A
510
51.441
9.105
9.652
1.00
18.04


ATOM
1096
CA
ILE
A
510
51.917
10.289
10.358
1.00
18.42


ATOM
1097
CB
ILE
A
510
51.516
10.297
11.851
1.00
16.95


ATOM
1098
CG2
ILE
A
510
52.019
11.575
12.505
1.00
17.62


ATOM
1099
CG1
ILE
A
510
49.989
10.212
12.002
1.00
16.30


ATOM
1100
CD1
ILE
A
510
49.236
11.393
11.424
1.00
17.39


ATOM
1101
C
ILE
A
510
53.433
10.298
10.275
1.00
18.57


ATOM
1102
O
ILE
A
510
54.100
9.418
10.816
1.00
18.85


ATOM
1103
N
LEU
A
511
53.976
11.298
9.588
1.00
19.12


ATOM
1104
CA
LEU
A
511
55.418
11.410
9.433
1.00
18.91


ATOM
1105
CB
LEU
A
511
55.769
11.695
7.972
1.00
17.90


ATOM
1106
CG
LEU
A
511
55.364
10.653
6.928
1.00
19.17


ATOM
1107
CD1
LEU
A
511
55.419
11.289
5.549
1.00
18.27


ATOM
1108
CD2
LEU
A
511
56.279
9.429
7.014
1.00
16.37


ATOM
1109
C
LEU
A
511
55.967
12.526
10.304
1.00
19.34


ATOM
1110
O
LEU
A
511
55.246
13.453
10.676
1.00
19.91


ATOM
1111
N
LEU
A
512
57.251
12.429
10.622
1.00
20.38


ATOM
1112
CA
LEU
A
512
57.928
13.434
11.429
1.00
22.06


ATOM
1113
CB
LEU
A
512
58.739
12.768
12.545
1.00
24.58


ATOM
1114
CG
LEU
A
512
58.000
12.360
13.812
1.00
26.71


ATOM
1115
CD1
LEU
A
512
58.905
11.544
14.724
1.00
27.64


ATOM
1116
CD2
LEU
A
512
57.537
13.619
14.514
1.00
29.31


ATOM
1117
C
LEU
A
512
58.866
14.244
10.551
1.00
21.66


ATOM
1118
O
LEU
A
512
59.627
13.677
9.761
1.00
20.77


ATOM
1119
N
ASP
A
513
58.808
15.566
10.686
1.00
22.75


ATOM
1120
CA
ASP
A
513
59.675
16.449
9.911
1.00
24.28


ATOM
1121
CB
ASP
A
513
59.031
17.826
9.743
1.00
25.47


ATOM
1122
CG
ASP
A
513
59.607
18.602
8.567
1.00
27.30


ATOM
1123
OD1
ASP
A
513
60.754
18.315
8.146
1.00
27.20


ATOM
1124
OD2
ASP
A
513
58.913
19.512
8.067
1.00
28.69


ATOM
1125
C
ASP
A
513
60.996
16.578
10.673
1.00
24.55


ATOM
1126
O
ASP
A
513
61.116
16.087
11.793
1.00
24.45


ATOM
1127
N
LYS
A
514
61.976
17.248
10.075
1.00
24.50


ATOM
1128
CA
LYS
A
514
63.289
17.405
10.694
1.00
25.34


ATOM
1129
CB
LYS
A
514
64.286
17.922
9.660
1.00
26.21


ATOM
1130
CG
LYS
A
514
63.951
19.297
9.124
1.00
28.18


ATOM
1131
CD
LYS
A
514
64.978
19.740
8.102
1.00
30.84


ATOM
1132
CE
LYS
A
514
64.762
21.187
7.709
1.00
31.77


ATOM
1133
NZ
LYS
A
514
63.452
21.388
7.045
1.00
33.28


ATOM
1134
C
LYS
A
514
63.299
18.320
11.915
1.00
25.71


ATOM
1135
O
LYS
A
514
64.280
18.357
12.658
1.00
25.54


ATOM
1136
N
ASP
A
515
62.209
19.053
12.116
1.00
25.46


ATOM
1137
CA
ASP
A
515
62.087
19.962
13.246
1.00
24.68


ATOM
1138
CB
ASP
A
515
61.316
21.222
12.830
1.00
26.41


ATOM
1139
CG
ASP
A
515
60.014
20.904
12.097
1.00
28.98


ATOM
1140
OD1
ASP
A
515
59.613
19.714
12.063
1.00
28.81


ATOM
1141
OD2
ASP
A
515
59.389
21.850
11.555
1.00
28.10


ATOM
1142
C
ASP
A
515
61.385
19.290
14.421
1.00
23.39


ATOM
1143
O
ASP
A
515
61.292
19.856
15.509
1.00
22.94


ATOM
1144
N
GLY
A
516
60.886
18.079
14.203
1.00
21.31


ATOM
1145
CA
GLY
A
516
60.207
17.375
15.274
1.00
20.30


ATOM
1146
C
GLY
A
516
58.695
17.476
15.227
1.00
19.36


ATOM
1147
O
GLY
A
516
58.000
16.860
16.033
1.00
20.02


ATOM
1148
N
HIS
A
517
58.175
18.262
14.293
1.00
19.59


ATOM
1149
CA
HIS
A
517
56.732
18.410
14.155
1.00
20.79


ATOM
1150
CB
HIS
A
517
56.394
19.796
13.618
1.00
21.14


ATOM
1151
CG
HIS
A
517
56.776
20.902
14.550
1.00
22.26


ATOM
1152
CD2
HIS
A
517
57.803
21.783
14.515
1.00
22.56


ATOM
1153
ND1
HIS
A
517
56.079
21.169
15.709
1.00
22.64


ATOM
1154
CE1
HIS
A
517
56.661
22.169
16.348
1.00
23.15


ATOM
1155
NE2
HIS
A
517
57.709
22.559
15.644
1.00
23.02


ATOM
1156
C
HIS
A
517
56.223
17.334
13.203
1.00
21.25


ATOM
1157
O
HIS
A
517
56.987
16.817
12.390
1.00
21.56


ATOM
1158
N
ILE
A
518
54.945
16.986
13.303
1.00
20.88


ATOM
1159
CA
ILE
A
518
54.409
15.953
12.432
1.00
22.70


ATOM
1160
CB
ILE
A
518
53.478
14.970
13.215
1.00
22.97


ATOM
1161
CG2
ILE
A
518
54.286
14.225
14.271
1.00
24.54


ATOM
1162
CG1
ILE
A
518
52.318
15.714
13.879
1.00
23.64


ATOM
1163
CD1
ILE
A
518
51.147
16.010
12.951
1.00
23.04


ATOM
1164
C
ILE
A
518
53.676
16.483
11.204
1.00
22.23


ATOM
1165
O
ILE
A
518
53.343
17.666
11.107
1.00
21.28


ATOM
1166
N
LYS
A
519
53.454
15.584
10.256
1.00
21.56


ATOM
1167
CA
LYS
A
519
52.748
15.907
9.033
1.00
20.61


ATOM
1168
CB
LYS
A
519
53.731
16.327
7.935
1.00
21.67


ATOM
1169
CG
LYS
A
519
53.957
17.838
7.872
1.00
21.69


ATOM
1170
CD
LYS
A
519
55.005
18.201
6.853
1.00
22.59


ATOM
1171
CE
LYS
A
519
55.246
19.704
6.800
1.00
22.86


ATOM
1172
NZ
LYS
A
519
54.122
20.434
6.147
1.00
23.05


ATOM
1173
C
LYS
A
519
51.939
14.706
8.583
1.00
20.45


ATOM
1174
O
LYS
A
519
52.455
13.591
8.510
1.00
19.68


ATOM
1175
N
ILE
A
520
50.659
14.935
8.308
1.00
19.04


ATOM
1176
CA
ILE
A
520
49.784
13.877
7.837
1.00
18.49


ATOM
1177
CB
ILE
A
520
48.309
14.288
7.978
1.00
19.91


ATOM
1178
CG2
ILE
A
520
47.412
13.244
7.334
1.00
19.22


ATOM
1179
CG1
ILE
A
520
47.969
14.480
9.464
1.00
19.20


ATOM
1180
CD1
ILE
A
520
46.572
15.018
9.729
1.00
20.35


ATOM
1181
C
ILE
A
520
50.115
13.645
6.360
1.00
19.25


ATOM
1182
O
ILE
A
520
50.351
14.601
5.613
1.00
18.82


ATOM
1183
N
ALA
A
521
50.147
12.380
5.949
1.00
18.64


ATOM
1184
CA
ALA
A
521
50.464
12.034
4.568
1.00
19.29


ATOM
1185
CB
ALA
A
521
51.893
11.486
4.483
1.00
20.21


ATOM
1186
C
ALA
A
521
49.491
11.022
3.968
1.00
19.71


ATOM
1187
O
ALA
A
521
48.763
10.343
4.692
1.00
18.05


ATOM
1188
N
ASP
A
522
49.501
10.935
2.639
1.00
18.55


ATOM
1189
CA
ASP
A
522
48.653
10.024
1.878
1.00
20.06


ATOM
1190
CB
ASP
A
522
48.794
8.580
2.373
1.00
20.92


ATOM
1191
CG
ASP
A
522
48.319
7.571
1.339
1.00
24.08


ATOM
1192
OD1
ASP
A
522
47.547
7.969
0.441
1.00
24.83


ATOM
1193
OD2
ASP
A
522
48.704
6.382
1.417
1.00
25.31


ATOM
1194
C
ASP
A
522
47.192
10.428
1.940
1.00
20.15


ATOM
1195
O
ASP
A
522
46.472
10.049
2.863
1.00
20.16


ATOM
1196
N
PHE
A
523
46.749
11.174
0.934
1.00
20.43


ATOM
1197
CA
PHE
A
523
45.373
11.649
0.899
1.00
21.18


ATOM
1198
CB
PHE
A
523
45.360
13.167
0.695
1.00
20.08


ATOM
1199
CG
PHE
A
523
46.182
13.920
1.707
1.00
19.62


ATOM
1200
CD1
PHE
A
523
47.416
14.455
1.358
1.00
19.23


ATOM
1201
CD2
PHE
A
523
45.733
14.070
3.019
1.00
19.33


ATOM
1202
CE1
PHE
A
523
48.196
15.133
2.300
1.00
20.66


ATOM
1203
CE2
PHE
A
523
46.502
14.742
3.969
1.00
18.29


ATOM
1204
CZ
PHE
A
523
47.738
15.278
3.610
1.00
17.84


ATOM
1205
C
PHE
A
523
44.539
10.975
−0.173
1.00
21.50


ATOM
1206
O
PHE
A
523
43.498
11.491
−0.575
1.00
22.40


ATOM
1207
N
GLY
A
524
44.982
9.805
−0.615
1.00
22.46


ATOM
1208
CA
GLY
A
524
44.261
9.091
−1.651
1.00
24.81


ATOM
1209
C
GLY
A
524
42.866
8.605
−1.296
1.00
25.97


ATOM
1210
O
GLY
A
524
42.076
8.307
−2.188
1.00
27.99


ATOM
1211
N
MET
A
525
42.542
8.534
−0.010
1.00
24.70


ATOM
1212
CA
MET
A
525
41.236
8.045
0.404
1.00
24.83


ATOM
1213
CB
MET
A
525
41.413
6.973
1.483
1.00
26.53


ATOM
1214
CG
MET
A
525
42.290
5.812
1.017
1.00
33.82


ATOM
1215
SD
MET
A
525
42.556
4.523
2.254
1.00
40.11


ATOM
1216
CE
MET
A
525
40.911
3.792
2.275
1.00
38.02


ATOM
1217
C
MET
A
525
40.278
9.131
0.888
1.00
23.45


ATOM
1218
O
MET
A
525
39.189
8.833
1.375
1.00
23.04


ATOM
1219
N
CYS
A
526
40.676
10.390
0.745
1.00
21.76


ATOM
1220
CA
CYS
A
526
39.827
11.494
1.173
1.00
21.47


ATOM
1221
CB
CYS
A
526
40.571
12.825
1.068
1.00
21.15


ATOM
1222
SG
CYS
A
526
41.970
12.999
2.168
1.00
22.41


ATOM
1223
C
CYS
A
526
38.551
11.608
0.352
1.00
21.18


ATOM
1224
O
CYS
A
526
38.493
11.195
−0.807
1.00
21.68


ATOM
1225
N
LYS
A
527
37.530
12.177
0.976
1.00
21.26


ATOM
1226
CA
LYS
A
527
36.244
12.422
0.337
1.00
20.63


ATOM
1227
CB
LYS
A
527
35.124
11.711
1.101
1.00
21.60


ATOM
1228
CG
LYS
A
527
33.745
11.808
0.443
1.00
24.61


ATOM
1229
CD
LYS
A
527
33.673
10.958
−0.815
1.00
25.95


ATOM
1230
CE
LYS
A
527
32.294
11.031
−1.459
1.00
28.67


ATOM
1231
NZ
LYS
A
527
32.222
10.153
−2.671
1.00
30.33


ATOM
1232
C
LYS
A
527
36.071
13.936
0.457
1.00
19.86


ATOM
1233
O
LYS
A
527
36.138
14.482
1.556
1.00
20.20


ATOM
1234
N
GLU
A
528
35.876
14.615
−0.666
1.00
19.60


ATOM
1235
CA
GLU
A
528
35.704
16.067
−0.664
1.00
19.76


ATOM
1236
CB
GLU
A
528
36.455
16.682
−1.838
1.00
21.13


ATOM
1237
CG
GLU
A
528
37.935
16.434
−1.810
1.00
22.94


ATOM
1238
CD
GLU
A
528
38.526
16.446
−3.193
1.00
24.78


ATOM
1239
OE1
GLU
A
528
38.133
15.575
−3.998
1.00
25.30


ATOM
1240
OE2
GLU
A
528
39.375
17.319
−3.478
1.00
26.54


ATOM
1241
C
GLU
A
528
34.240
16.467
−0.757
1.00
19.00


ATOM
1242
O
GLU
A
528
33.358
15.615
−0.798
1.00
17.13


ATOM
1243
N
ASN
A
529
34.001
17.775
−0.796
1.00
20.30


ATOM
1244
CA
ASN
A
529
32.655
18.342
−0.879
1.00
21.66


ATOM
1245
CB
ASN
A
529
31.993
17.982
−2.215
1.00
22.30


ATOM
1246
CG
ASN
A
529
31.283
19.174
−2.859
1.00
25.51


ATOM
1247
OD1
ASN
A
529
30.672
19.053
−3.924
1.00
25.61


ATOM
1248
ND2
ASN
A
529
31.368
20.332
−2.214
1.00
24.70


ATOM
1249
C
ASN
A
529
31.790
17.854
0.273
1.00
22.28


ATOM
1250
O
ASN
A
529
30.571
17.804
0.173
1.00
23.01


ATOM
1251
N
MET
A
530
32.433
17.485
1.372
1.00
23.55


ATOM
1252
CA
MET
A
530
31.720
17.032
2.548
1.00
24.81


ATOM
1253
CB
MET
A
530
32.573
16.021
3.305
1.00
25.43


ATOM
1254
CG
MET
A
530
32.747
14.702
2.561
1.00
23.70


ATOM
1255
SD
MET
A
530
31.167
13.851
2.400
1.00
24.80


ATOM
1256
CE
MET
A
530
31.074
13.081
3.935
1.00
24.48


ATOM
1257
C
MET
A
530
31.460
18.280
3.377
1.00
26.65


ATOM
1258
O
MET
A
530
32.145
18.562
4.356
1.00
27.54


ATOM
1259
N
LEU
A
531
30.457
19.030
2.959
1.00
27.74


ATOM
1260
CA
LEU
A
531
30.066
20.265
3.612
1.00
28.65


ATOM
1261
CB
LEU
A
531
30.125
21.383
2.543
1.00
30.08


ATOM
1262
CG
LEU
A
531
31.569
21.373
2.004
1.00
31.31


ATOM
1263
CD1
LEU
A
531
31.756
22.247
0.787
1.00
32.06


ATOM
1264
CD2
LEU
A
531
32.496
21.745
3.120
1.00
32.22


ATOM
1265
C
LEU
A
531
28.674
20.223
4.220
1.00
28.40


ATOM
1266
O
LEU
A
531
27.791
19.556
3.691
1.00
27.67


ATOM
1267
N
GLY
A
532
28.494
20.989
5.291
1.00
28.00


ATOM
1268
CA
GLY
A
532
27.211
21.027
5.954
1.00
28.28


ATOM
1269
C
GLY
A
532
26.782
19.666
6.486
1.00
27.84


ATOM
1270
O
GLY
A
532
27.524
19.017
7.225
1.00
27.59


ATOM
1271
N
ASP
A
533
25.588
19.230
6.093
1.00
27.81


ATOM
1272
CA
ASP
A
533
25.069
17.944
6.534
1.00
28.45


ATOM
1273
CB
ASP
A
533
23.546
18.014
6.716
1.00
30.53


ATOM
1274
CG
ASP
A
533
22.805
18.320
5.417
1.00
33.51


ATOM
1275
OD1
ASP
A
533
23.327
18.004
4.326
1.00
34.72


ATOM
1276
OD2
ASP
A
533
21.680
18.864
5.485
1.00
36.06


ATOM
1277
C
ASP
A
533
25.407
16.812
5.565
1.00
27.34


ATOM
1278
O
ASP
A
533
24.810
15.746
5.613
1.00
27.74


ATOM
1279
N
ALA
A
534
26.369
17.039
4.683
1.00
25.29


ATOM
1280
CA
ALA
A
534
26.740
16.018
3.721
1.00
23.54


ATOM
1281
CB
ALA
A
534
27.753
16.582
2.728
1.00
20.51


ATOM
1282
C
ALA
A
534
27.299
14.767
4.393
1.00
23.05


ATOM
1283
O
ALA
A
534
28.096
14.849
5.325
1.00
23.22


ATOM
1284
N
LYS
A
535
26.867
13.603
3.919
1.00
22.84


ATOM
1285
CA
LYS
A
535
27.365
12.331
4.442
1.00
23.86


ATOM
1286
CB
LYS
A
535
26.342
11.696
5.357
1.00
24.88


ATOM
1287
CG
LYS
A
535
26.270
12.449
6.653
1.00
27.41


ATOM
1288
CD
LYS
A
535
25.282
11.871
7.646
1.00
29.64


ATOM
1289
CE
LYS
A
535
25.147
12.824
8.869
1.00
32.50


ATOM
1290
NZ
LYS
A
535
24.325
12.249
10.014
1.00
36.38


ATOM
1291
C
LYS
A
535
27.692
11.445
3.252
1.00
23.49


ATOM
1292
O
LYS
A
535
27.214
11.692
2.144
1.00
23.82


ATOM
1293
N
THR
A
536
28.556
10.455
3.451
1.00
22.12


ATOM
1294
CA
THR
A
536
28.924
9.545
2.374
1.00
20.15


ATOM
1295
CB
THR
A
536
30.354
9.807
1.869
1.00
19.00


ATOM
1296
OG1
THR
A
536
30.545
9.092
0.650
1.00
18.73


ATOM
1297
CG2
THR
A
536
31.398
9.355
2.884
1.00
18.42


ATOM
1298
C
THR
A
536
28.757
8.107
2.860
1.00
19.94


ATOM
1299
O
THR
A
536
28.426
7.884
4.024
1.00
19.89


ATOM
1300
N
ASN
A
537
28.997
7.131
1.989
1.00
19.53


ATOM
1301
CA
ASN
A
537
28.763
5.745
2.382
1.00
18.63


ATOM
1302
CB
ASN
A
537
27.359
5.349
1.937
1.00
18.00


ATOM
1303
CG
ASN
A
537
27.148
5.571
0.452
1.00
18.88


ATOM
1304
OD1
ASN
A
537
28.109
5.756
−0.302
1.00
17.85


ATOM
1305
ND2
ASN
A
537
25.892
5.549
0.020
1.00
19.43


ATOM
1306
C
ASN
A
537
29.728
4.658
1.911
1.00
18.16


ATOM
1307
O
ASN
A
537
29.398
3.471
1.991
1.00
17.90


ATOM
1308
N
THR
A
538
30.902
5.021
1.418
1.00
17.96


ATOM
1309
CA
THR
A
538
31.816
3.980
0.963
1.00
18.05


ATOM
1310
CG2
THR
A
538
33.680
3.407
−0.628
1.00
15.91


ATOM
1311
C
THR
A
538
32.488
3.279
2.151
1.00
19.24


ATOM
1312
O
THR
A
538
33.025
3.933
3.049
1.00
19.51


ATOM
1313
OG1
THR
A
538
32.329
5.358
−1.001
1.00
20.05


ATOM
1314
CB
THR
A
538
32.919
4.549
0.031
1.00
17.40


ATOM
1315
N
PHE
A
539
32.441
1.948
2.172
1.00
19.27


ATOM
1316
CA
PHE
A
539
33.095
1.186
3.239
1.00
19.63


ATOM
1317
CB
PHE
A
539
32.643
−0.283
3.222
1.00
19.06


ATOM
1318
CG
PHE
A
539
33.265
−1.131
4.308
1.00
18.84


ATOM
1319
CD1
PHE
A
539
32.556
−1.435
5.468
1.00
17.91


ATOM
1320
CD2
PHE
A
539
34.561
−1.623
4.173
1.00
18.45


ATOM
1321
CE1
PHE
A
539
33.131
−2.222
6.475
1.00
19.16


ATOM
1322
CE2
PHE
A
539
35.145
−2.411
5.179
1.00
17.02


ATOM
1323
CZ
PHE
A
539
34.431
−2.710
6.325
1.00
16.34


ATOM
1324
C
PHE
A
539
34.593
1.243
2.943
1.00
20.41


ATOM
1325
O
PHE
A
539
35.040
0.757
1.907
1.00
19.47


ATOM
1326
N
CYS
A
540
35.373
1.848
3.831
1.00
22.16


ATOM
1327
CA
CYS
A
540
36.814
1.916
3.597
1.00
23.85


ATOM
1328
CB
CYS
A
540
37.123
2.913
2.478
1.00
24.97


ATOM
1329
SG
CYS
A
540
36.649
4.612
2.834
1.00
28.24


ATOM
1330
C
CYS
A
540
37.621
2.272
4.839
1.00
22.97


ATOM
1331
O
CYS
A
540
37.072
2.699
5.847
1.00
23.35


ATOM
1332
N
GLY
A
541
38.933
2.079
4.745
1.00
23.63


ATOM
1333
CA
GLY
A
541
39.827
2.365
5.851
1.00
23.21


ATOM
1334
C
GLY
A
541
40.575
1.112
6.270
1.00
23.07


ATOM
1335
O
GLY
A
541
40.190
0.004
5.898
1.00
23.87


ATOM
1336
N
THR
A
542
41.651
1.285
7.031
1.00
22.53


ATOM
1337
CA
THR
A
542
42.447
0.169
7.523
1.00
21.10


ATOM
1338
CB
THR
A
542
43.800
0.665
8.059
1.00
21.37


ATOM
1339
OG1
THR
A
542
44.521
1.295
6.992
1.00
23.21


ATOM
1340
CG2
THR
A
542
44.627
−0.488
8.618
1.00
20.71


ATOM
1341
C
THR
A
542
41.623
−0.425
8.656
1.00
21.55


ATOM
1342
O
THR
A
542
41.233
0.289
9.579
1.00
20.88


ATOM
1343
N
PRO
A
543
41.345
−1.738
8.599
1.00
20.55


ATOM
1344
CD
PRO
A
543
41.784
−2.675
7.553
1.00
21.83


ATOM
1345
CA
PRO
A
543
40.548
−2.431
9.619
1.00
20.72


ATOM
1346
CB
PRO
A
543
40.818
−3.921
9.343
1.00
20.34


ATOM
1347
CG
PRO
A
543
41.951
−3.942
8.325
1.00
22.49


ATOM
1348
C
PRO
A
543
40.721
−2.053
11.090
1.00
20.46


ATOM
1349
O
PRO
A
543
39.727
−1.836
11.789
1.00
20.10


ATOM
1350
N
ASP
A
544
41.957
−1.973
11.570
1.00
19.91


ATOM
1351
CA
ASP
A
544
42.190
−1.614
12.970
1.00
20.86


ATOM
1352
CB
ASP
A
544
43.688
−1.532
13.275
1.00
23.86


ATOM
1353
CG
ASP
A
544
44.310
−2.879
13.543
1.00
25.82


ATOM
1354
OD1
ASP
A
544
43.808
−3.607
14.418
1.00
29.20


ATOM
1355
OD2
ASP
A
544
45.314
−3.202
12.888
1.00
29.50


ATOM
1356
C
ASP
A
544
41.574
−0.271
13.344
1.00
19.45


ATOM
1357
O
ASP
A
544
41.189
−0.064
14.495
1.00
18.17


ATOM
1358
N
TYR
A
545
41.488
0.630
12.366
1.00
18.20


ATOM
1359
CA
TYR
A
545
40.979
1.982
12.575
1.00
17.69


ATOM
1360
CB
TYR
A
545
41.909
2.987
11.893
1.00
16.32


ATOM
1361
CG
TYR
A
545
43.359
2.893
12.309
1.00
18.41


ATOM
1362
CD1
TYR
A
545
44.213
1.935
11.748
1.00
17.28


ATOM
1363
CE1
TYR
A
545
45.559
1.867
12.122
1.00
17.83


ATOM
1364
CD2
TYR
A
545
43.885
3.771
13.258
1.00
18.29


ATOM
1365
CE2
TYR
A
545
45.221
3.707
13.641
1.00
16.95


ATOM
1366
CZ
TYR
A
545
46.051
2.761
13.069
1.00
17.88


ATOM
1367
OH
TYR
A
545
47.382
2.746
13.419
1.00
19.97


ATOM
1368
C
TYR
A
545
39.553
2.283
12.115
1.00
17.84


ATOM
1369
O
TYR
A
545
39.072
3.401
12.298
1.00
16.52


ATOM
1370
N
ILE
A
546
38.875
1.309
11.517
1.00
17.86


ATOM
1371
CA
ILE
A
546
37.518
1.540
11.032
1.00
17.94


ATOM
1372
CB
ILE
A
546
37.026
0.344
10.201
1.00
18.45


ATOM
1373
CG2
ILE
A
546
35.580
0.552
9.783
1.00
18.31


ATOM
1374
CG1
ILE
A
546
37.913
0.192
8.964
1.00
20.01


ATOM
1375
CD1
ILE
A
546
37.523
−0.974
8.067
1.00
20.46


ATOM
1376
C
ILE
A
546
36.500
1.845
12.129
1.00
17.48


ATOM
1377
O
ILE
A
546
36.361
1.090
13.091
1.00
17.82


ATOM
1378
N
ALA
A
547
35.785
2.957
11.973
1.00
17.10


ATOM
1379
CA
ALA
A
547
34.778
3.373
12.948
1.00
16.70


ATOM
1380
CB
ALA
A
547
34.341
4.806
12.671
1.00
16.80


ATOM
1381
C
ALA
A
547
33.557
2.454
12.961
1.00
17.48


ATOM
1382
O
ALA
A
547
33.155
1.905
11.934
1.00
18.59


ATOM
1383
N
PRO
A
548
32.943
2.281
14.136
1.00
16.72


ATOM
1384
CD
PRO
A
548
33.309
2.870
15.435
1.00
15.05


ATOM
1385
CA
PRO
A
548
31.767
1.425
14.259
1.00
17.04


ATOM
1386
CB
PRO
A
548
31.451
1.481
15.757
1.00
17.00


ATOM
1387
CG
PRO
A
548
32.002
2.814
16.180
1.00
16.79


ATOM
1388
C
PRO
A
548
30.580
1.834
13.391
1.00
18.54


ATOM
1389
O
PRO
A
548
29.833
0.968
12.935
1.00
19.16


ATOM
1390
N
GLU
A
549
30.395
3.135
13.153
1.00
17.85


ATOM
1391
CA
GLU
A
549
29.262
3.547
12.340
1.00
17.87


ATOM
1392
CB
GLU
A
549
29.072
5.079
12.337
1.00
17.17


ATOM
1393
CG
GLU
A
549
30.270
5.928
11.945
1.00
15.50


ATOM
1394
CD
GLU
A
549
31.084
6.387
13.142
1.00
17.51


ATOM
1395
OE1
GLU
A
549
31.651
7.504
13.084
1.00
17.84


ATOM
1396
OE2
GLU
A
549
31.163
5.634
14.140
1.00
15.71


ATOM
1397
C
GLU
A
549
29.378
3.007
10.919
1.00
18.90


ATOM
1398
O
GLU
A
549
28.358
2.755
10.268
1.00
18.05


ATOM
1399
N
ILE
A
550
30.611
2.819
10.447
1.00
17.17


ATOM
1400
CA
ILE
A
550
30.841
2.274
9.115
1.00
17.57


ATOM
1401
CB
ILE
A
550
32.313
2.469
8.652
1.00
15.79


ATOM
1402
CG2
ILE
A
550
32.618
1.589
7.453
1.00
14.30


ATOM
1403
CG1
ILE
A
550
32.553
3.927
8.264
1.00
16.11


ATOM
1404
CD1
ILE
A
550
34.010
4.251
8.007
1.00
15.68


ATOM
1405
C
ILE
A
550
30.524
0.779
9.163
1.00
18.67


ATOM
1406
O
ILE
A
550
29.876
0.248
8.264
1.00
18.69


ATOM
1407
N
LEU
A
551
30.973
0.110
10.221
1.00
18.36


ATOM
1408
CA
LEU
A
551
30.716
−1.320
10.375
1.00
20.69


ATOM
1409
CB
LEU
A
551
31.422
−1.860
11.622
1.00
19.36


ATOM
1410
CG
LEU
A
551
32.950
−1.777
11.604
1.00
19.90


ATOM
1411
CD1
LEU
A
551
33.495
−2.356
12.895
1.00
17.81


ATOM
1412
CD2
LEU
A
551
33.502
−2.534
10.389
1.00
17.70


ATOM
1413
C
LEU
A
551
29.221
−1.618
10.475
1.00
21.63


ATOM
1414
O
LEU
A
551
28.772
−2.680
10.048
1.00
21.95


ATOM
1415
N
LEU
A
552
28.457
−0.683
11.040
1.00
22.00


ATOM
1416
CA
LEU
A
552
27.017
−0.856
11.192
1.00
23.63


ATOM
1417
CB
LEU
A
552
26.507
−0.081
12.409
1.00
25.79


ATOM
1418
CG
LEU
A
552
26.980
−0.550
13.792
1.00
28.51


ATOM
1419
CD1
LEU
A
552
26.501
0.419
14.866
1.00
29.25


ATOM
1420
CD2
LEU
A
552
26.443
−1.949
14.062
1.00
30.34


ATOM
1421
C
LEU
A
552
26.264
−0.399
9.946
1.00
23.90


ATOM
1422
O
LEU
A
552
25.034
−0.424
9.911
1.00
24.62


ATOM
1423
N
GLY
A
553
27.009
0.031
8.936
1.00
23.62


ATOM
1424
CA
GLY
A
553
26.407
0.450
7.684
1.00
23.80


ATOM
1425
C
GLY
A
553
25.667
1.778
7.635
1.00
23.76


ATOM
1426
O
GLY
A
553
24.747
1.937
6.833
1.00
23.17


ATOM
1427
N
GLN
A
554
26.063
2.746
8.463
1.00
22.25


ATOM
1428
CA
GLN
A
554
25.383
4.049
8.458
1.00
22.80


ATOM
1429
CB
GLN
A
554
25.355
4.691
9.848
1.00
25.52


ATOM
1430
CG
GLN
A
554
24.839
3.820
10.969
1.00
30.22


ATOM
1431
CD
GLN
A
554
25.167
4.358
12.362
1.00
34.81


ATOM
1432
OE1
GLN
A
554
25.229
3.649
13.350
1.00
37.99


ATOM
1433
NE2
GLN
A
554
25.418
5.684
12.416
1.00
35.48


ATOM
1434
C
GLN
A
554
26.099
5.044
7.550
1.00
21.79


ATOM
1435
O
GLN
A
554
27.319
4.996
7.419
1.00
22.01


ATOM
1436
N
LYS
A
555
25.348
5.959
6.938
1.00
21.37


ATOM
1437
CA
LYS
A
555
25.941
7.027
6.107
1.00
22.83


ATOM
1438
CB
LYS
A
555
24.832
7.920
5.511
1.00
23.48


ATOM
1439
CG
LYS
A
555
24.206
7.374
4.230
1.00
28.36


ATOM
1440
CD
LYS
A
555
23.078
8.260
3.663
1.00
31.39


ATOM
1441
CE
LYS
A
555
21.670
7.676
3.931
1.00
35.16


ATOM
1442
NZ
LYS
A
555
21.143
7.934
5.313
1.00
38.46


ATOM
1443
C
LYS
A
555
26.773
7.813
7.147
1.00
21.05


ATOM
1444
O
LYS
A
555
26.330
7.969
8.288
1.00
20.47


ATOM
1445
N
TYR
A
556
27.955
8.308
6.784
1.00
19.68


ATOM
1446
CA
TYR
A
556
28.788
9.006
7.777
1.00
18.52


ATOM
1447
CB
TYR
A
556
29.838
8.034
8.322
1.00
15.77


ATOM
1448
CG
TYR
A
556
30.772
7.535
7.242
1.00
14.96


ATOM
1449
CD1
TYR
A
556
31.900
8.273
6.872
1.00
13.59


ATOM
1450
CE1
TYR
A
556
32.712
7.869
5.814
1.00
13.56


ATOM
1451
CD2
TYR
A
556
30.479
6.369
6.527
1.00
14.85


ATOM
1452
CE2
TYR
A
556
31.277
5.954
5.463
1.00
14.04


ATOM
1453
CZ
TYR
A
556
32.393
6.710
5.108
1.00
14.22


ATOM
1454
OH
TYR
A
556
33.178
6.326
4.046
1.00
12.73


ATOM
1455
C
TYR
A
556
29.495
10.265
7.298
1.00
18.90


ATOM
1456
O
TYR
A
556
29.526
10.566
6.107
1.00
18.27


ATOM
1457
N
ASN
A
557
30.072
10.991
8.254
1.00
20.62


ATOM
1458
CA
ASN
A
557
30.811
12.215
7.968
1.00
21.51


ATOM
1459
CB
ASN
A
557
30.007
13.448
8.397
1.00
22.20


ATOM
1460
CG
ASN
A
557
29.695
13.457
9.873
1.00
23.40


ATOM
1461
OD1
ASN
A
557
30.404
12.850
10.677
1.00
25.63


ATOM
1462
ND2
ASN
A
557
28.640
14.169
10.247
1.00
25.64


ATOM
1463
C
ASN
A
557
32.169
12.192
8.682
1.00
21.51


ATOM
1464
O
ASN
A
557
32.709
11.119
8.942
1.00
21.91


ATOM
1465
N
HIS
A
558
32.706
13.366
9.014
1.00
20.63


ATOM
1466
CA
HIS
A
558
34.017
13.466
9.664
1.00
20.92


ATOM
1467
CB
HIS
A
558
34.383
14.934
9.913
1.00
23.43


ATOM
1468
CG
HIS
A
558
33.599
15.578
11.013
1.00
26.42


ATOM
1469
CD2
HIS
A
558
33.975
16.006
12.242
1.00
27.12


ATOM
1470
ND1
HIS
A
558
32.249
15.845
10.912
1.00
28.39


ATOM
1471
CE1
HIS
A
558
31.828
16.409
12.031
1.00
27.49


ATOM
1472
NE2
HIS
A
558
32.856
16.518
12.854
1.00
27.42


ATOM
1473
C
HIS
A
558
34.145
12.697
10.979
1.00
19.52


ATOM
1474
O
HIS
A
558
35.248
12.489
11.469
1.00
15.91


ATOM
1475
N
SER
A
559
33.018
12.286
11.550
1.00
18.52


ATOM
1476
CA
SER
A
559
33.037
11.538
12.803
1.00
18.47


ATOM
1477
CB
SER
A
559
31.623
11.075
13.173
1.00
18.34


ATOM
1478
OG
SER
A
559
31.176
10.056
12.302
1.00
19.25


ATOM
1479
C
SER
A
559
33.947
10.315
12.751
1.00
17.88


ATOM
1480
O
SER
A
559
34.505
9.914
13.776
1.00
17.73


ATOM
1481
N
VAL
A
560
34.084
9.710
11.569
1.00
16.09


ATOM
1482
CA
VAL
A
560
34.917
8.526
11.443
1.00
15.29


ATOM
1483
CB
VAL
A
560
34.743
7.832
10.055
1.00
15.81


ATOM
1484
CG1
VAL
A
560
33.267
7.487
9.838
1.00
13.22


ATOM
1485
CG2
VAL
A
560
35.261
8.729
8.929
1.00
15.40


ATOM
1486
C
VAL
A
560
36.384
8.846
11.681
1.00
15.76


ATOM
1487
O
VAL
A
560
37.136
7.995
12.152
1.00
15.26


ATOM
1488
N
ASP
A
561
36.801
10.072
11.375
1.00
15.18


ATOM
1489
CA
ASP
A
561
38.196
10.424
11.600
1.00
14.98


ATOM
1490
CB
ASP
A
561
38.574
11.743
10.922
1.00
14.46


ATOM
1491
CG
ASP
A
561
38.593
11.642
9.407
1.00
15.59


ATOM
1492
OD1
ASP
A
561
38.836
10.537
8.871
1.00
15.64


ATOM
1493
OD2
ASP
A
561
38.379
12.683
8.748
1.00
16.11


ATOM
1494
C
ASP
A
561
38.481
10.542
13.088
1.00
14.85


ATOM
1495
O
ASP
A
561
39.591
10.251
13.529
1.00
12.08


ATOM
1496
N
TRP
A
562
37.484
10.969
13.860
1.00
14.47


ATOM
1497
CA
TRP
A
562
37.681
11.124
15.299
1.00
16.86


ATOM
1498
CB
TRP
A
562
36.569
11.992
15.900
1.00
15.19


ATOM
1499
CG
TRP
A
562
36.704
13.416
15.419
1.00
17.27


ATOM
1500
CD2
TRP
A
562
37.832
14.281
15.622
1.00
17.57


ATOM
1501
CE2
TRP
A
562
37.581
15.471
14.905
1.00
17.29


ATOM
1502
CE3
TRP
A
562
39.035
14.161
16.339
1.00
16.59


ATOM
1503
CD1
TRP
A
562
35.837
14.102
14.616
1.00
17.03


ATOM
1504
NE1
TRP
A
562
36.359
15.336
14.300
1.00
17.38


ATOM
1505
CZ2
TRP
A
562
38.487
16.539
14.880
1.00
17.77


ATOM
1506
CZ3
TRP
A
562
39.940
15.221
16.314
1.00
18.82


ATOM
1507
CH2
TRP
A
562
39.660
16.397
15.589
1.00
18.40


ATOM
1508
C
TRP
A
562
37.803
9.786
16.006
1.00
16.65


ATOM
1509
O
TRP
A
562
38.416
9.697
17.063
1.00
16.32


ATOM
1510
N
TRP
A
563
37.232
8.742
15.412
1.00
17.84


ATOM
1511
CA
TRP
A
563
37.343
7.407
15.983
1.00
16.49


ATOM
1512
CB
TRP
A
563
36.315
6.466
15.364
1.00
16.30


ATOM
1513
CG
TRP
A
563
36.466
5.049
15.826
1.00
15.78


ATOM
1514
CD2
TRP
A
563
35.790
4.435
16.927
1.00
16.38


ATOM
1515
CE2
TRP
A
563
36.280
3.114
17.033
1.00
16.34


ATOM
1516
CE3
TRP
A
563
34.816
4.872
17.836
1.00
16.67


ATOM
1517
CD1
TRP
A
563
37.312
4.106
15.322
1.00
13.61


ATOM
1518
NE1
TRP
A
563
37.209
2.942
16.040
1.00
16.49


ATOM
1519
CZ2
TRP
A
563
35.831
2.225
18.009
1.00
15.68


ATOM
1520
CZ3
TRP
A
563
34.366
3.984
18.813
1.00
16.70


ATOM
1521
CH2
TRP
A
563
34.876
2.674
18.889
1.00
17.15


ATOM
1522
C
TRP
A
563
38.756
6.908
15.684
1.00
17.23


ATOM
1523
O
TRP
A
563
39.465
6.426
16.574
1.00
16.67


ATOM
1524
N
SER
A
564
39.172
7.036
14.428
1.00
17.73


ATOM
1525
CA
SER
A
564
40.510
6.609
14.034
1.00
17.56


ATOM
1526
CB
SER
A
564
40.743
6.896
12.553
1.00
18.31


ATOM
1527
OG
SER
A
564
39.776
6.222
11.771
1.00
24.56


ATOM
1528
C
SER
A
564
41.568
7.328
14.867
1.00
17.10


ATOM
1529
O
SER
A
564
42.596
6.744
15.213
1.00
15.95


ATOM
1530
N
PHE
A
565
41.315
8.602
15.172
1.00
16.47


ATOM
1531
CA
PHE
A
565
42.232
9.399
15.981
1.00
15.31


ATOM
1532
CB
PHE
A
565
41.700
10.838
16.121
1.00
15.68


ATOM
1533
CG
PHE
A
565
42.493
11.701
17.069
1.00
15.08


ATOM
1534
CD1
PHE
A
565
43.754
12.184
16.725
1.00
14.90


ATOM
1535
CD2
PHE
A
565
41.966
12.039
18.309
1.00
16.71


ATOM
1536
CE1
PHE
A
565
44.476
12.996
17.608
1.00
16.17


ATOM
1537
CE2
PHE
A
565
42.680
12.853
19.202
1.00
15.19


ATOM
1538
CZ
PHE
A
565
43.934
13.331
18.848
1.00
14.70


ATOM
1539
C
PHE
A
565
42.354
8.745
17.353
1.00
14.00


ATOM
1540
O
PHE
A
565
43.453
8.607
17.889
1.00
15.28


ATOM
1541
N
GLY
A
566
41.221
8.346
17.922
1.00
12.97


ATOM
1542
CA
GLY
A
566
41.242
7.685
19.214
1.00
14.08


ATOM
1543
C
GLY
A
566
42.097
6.423
19.184
1.00
15.08


ATOM
1544
O
GLY
A
566
42.873
6.156
20.108
1.00
13.47


ATOM
1545
N
VAL
A
567
41.961
5.643
18.114
1.00
15.37


ATOM
1546
CA
VAL
A
567
42.729
4.414
17.977
1.00
15.73


ATOM
1547
CB
VAL
A
567
42.344
3.644
16.698
1.00
15.71


ATOM
1548
CG1
VAL
A
567
43.162
2.361
16.596
1.00
15.31


ATOM
1549
CG2
VAL
A
567
40.853
3.318
16.714
1.00
16.84


ATOM
1550
C
VAL
A
567
44.205
4.762
17.914
1.00
15.83


ATOM
1551
O
VAL
A
567
45.028
4.147
18.597
1.00
16.87


ATOM
1552
N
LEU
A
568
44.525
5.761
17.101
1.00
15.86


ATOM
1553
CA
LEU
A
568
45.895
6.228
16.924
1.00
16.67


ATOM
1554
CB
LEU
A
568
45.918
7.345
15.876
1.00
16.39


ATOM
1555
CG
LEU
A
568
47.275
7.815
15.347
1.00
18.99


ATOM
1556
CD1
LEU
A
568
47.061
8.561
14.034
1.00
16.82


ATOM
1557
CD2
LEU
A
568
47.978
8.712
16.375
1.00
17.66


ATOM
1558
C
LEU
A
568
46.501
6.729
18.242
1.00
16.60


ATOM
1559
O
LEU
A
568
47.652
6.419
18.569
1.00
15.53


ATOM
1560
N
LEU
A
569
45.730
7.509
18.995
1.00
15.33


ATOM
1561
CA
LEU
A
569
46.218
8.030
20.269
1.00
15.32


ATOM
1562
CB
LEU
A
569
45.227
9.038
20.851
1.00
13.60


ATOM
1563
CG
LEU
A
569
45.501
9.573
22.264
1.00
13.58


ATOM
1564
CD1
LEU
A
569
46.914
10.130
22.364
1.00
12.08


ATOM
1565
CD2
LEU
A
569
44.470
10.648
22.586
1.00
12.30


ATOM
1566
C
LEU
A
569
46.425
6.879
21.248
1.00
15.28


ATOM
1567
O
LEU
A
569
47.431
6.829
21.946
1.00
15.83


ATOM
1568
N
TYR
A
570
45.467
5.958
21.297
1.00
14.84


ATOM
1569
CA
TYR
A
570
45.567
4.799
22.173
1.00
15.24


ATOM
1570
CB
TYR
A
570
44.343
3.891
21.980
1.00
15.81


ATOM
1571
CG
TYR
A
570
44.328
2.641
22.838
1.00
16.40


ATOM
1572
CD1
TYR
A
570
45.140
1.549
22.530
1.00
16.48


ATOM
1573
CE1
TYR
A
570
45.137
0.402
23.321
1.00
15.88


ATOM
1574
CD2
TYR
A
570
43.508
2.556
23.965
1.00
15.81


ATOM
1575
CE2
TYR
A
570
43.498
1.417
24.762
1.00
14.45


ATOM
1576
CZ
TYR
A
570
44.314
0.341
24.434
1.00
16.92


ATOM
1577
OH
TYR
A
570
44.293
−0.803
25.204
1.00
15.75


ATOM
1578
C
TYR
A
570
46.860
4.053
21.846
1.00
15.87


ATOM
1579
O
TYR
A
570
47.621
3.695
22.743
1.00
14.37


ATOM
1580
N
GLU
A
571
47.126
3.845
20.560
1.00
16.10


ATOM
1581
CA
GLU
A
571
48.339
3.145
20.151
1.00
17.33


ATOM
1582
CB
GLU
A
571
48.355
2.918
18.640
1.00
18.05


ATOM
1583
CG
GLU
A
571
47.252
2.011
18.118
1.00
20.46


ATOM
1584
CD
GLU
A
571
47.329
1.830
16.610
1.00
23.05


ATOM
1585
OE1
GLU
A
571
47.545
2.837
15.902
1.00
23.73


ATOM
1586
OE2
GLU
A
571
47.165
0.689
16.126
1.00
24.78


ATOM
1587
C
GLU
A
571
49.629
3.860
20.561
1.00
17.33


ATOM
1588
O
GLU
A
571
50.577
3.216
20.980
1.00
17.42


ATOM
1589
N
MET
A
572
49.677
5.183
20.434
1.00
17.45


ATOM
1590
CA
MET
A
572
50.883
5.917
20.805
1.00
17.86


ATOM
1591
CB
MET
A
572
50.745
7.411
20.491
1.00
15.64


ATOM
1592
CG
MET
A
572
50.800
7.768
19.015
1.00
15.50


ATOM
1593
SD
MET
A
572
51.162
9.527
18.803
1.00
15.78


ATOM
1594
CE
MET
A
572
49.593
10.292
19.306
1.00
11.33


ATOM
1595
C
MET
A
572
51.209
5.770
22.288
1.00
17.96


ATOM
1596
O
MET
A
572
52.379
5.709
22.679
1.00
17.73


ATOM
1597
N
LEU
A
573
50.163
5.715
23.106
1.00
18.08


ATOM
1598
CA
LEU
A
573
50.313
5.621
24.559
1.00
20.18


ATOM
1599
CB
LEU
A
573
49.114
6.259
25.252
1.00
19.31


ATOM
1600
CG
LEU
A
573
48.880
7.763
25.185
1.00
20.70


ATOM
1601
CD1
LEU
A
573
47.441
8.038
25.613
1.00
17.92


ATOM
1602
CD2
LEU
A
573
49.874
8.485
26.113
1.00
19.54


ATOM
1603
C
LEU
A
573
50.462
4.222
25.122
1.00
20.83


ATOM
1604
O
LEU
A
573
51.148
4.018
26.127
1.00
20.62


ATOM
1605
N
ILE
A
574
49.807
3.264
24.477
1.00
20.98


ATOM
1606
CA
ILE
A
574
49.807
1.893
24.957
1.00
22.95


ATOM
1607
CB
ILE
A
574
48.365
1.340
24.966
1.00
23.26


ATOM
1608
CG2
ILE
A
574
48.345
−0.051
25.555
1.00
23.31


ATOM
1609
CG1
ILE
A
574
47.449
2.275
25.768
1.00
22.98


ATOM
1610
CD1
ILE
A
574
47.864
2.457
27.215
1.00
25.32


ATOM
1611
C
ILE
A
574
50.706
0.954
24.167
1.00
23.41


ATOM
1612
O
ILE
A
574
51.141
−0.073
24.683
1.00
23.85


ATOM
1613
N
GLY
A
575
50.977
1.302
22.914
1.00
23.52


ATOM
1614
CA
GLY
A
575
51.836
0.468
22.100
1.00
24.90


ATOM
1615
C
GLY
A
575
51.135
−0.756
21.542
1.00
25.99


ATOM
1616
O
GLY
A
575
51.775
−1.630
20.959
1.00
25.65


ATOM
1617
N
GLN
A
576
49.821
−0.809
21.729
1.00
25.92


ATOM
1618
CA
GLN
A
576
48.982
−1.899
21.240
1.00
26.08


ATOM
1619
CB
GLN
A
576
48.544
−2.817
22.384
1.00
29.36


ATOM
1620
CG
GLN
A
576
49.638
−3.531
23.145
1.00
36.00


ATOM
1621
CD
GLN
A
576
49.063
−4.335
24.296
1.00
39.14


ATOM
1622
OE1
GLN
A
576
48.967
−3.853
25.427
1.00
42.47


ATOM
1623
NE2
GLN
A
576
48.648
−5.560
24.006
1.00
41.45


ATOM
1624
C
GLN
A
576
47.719
−1.259
20.678
1.00
24.01


ATOM
1625
O
GLN
A
576
47.381
−0.130
21.040
1.00
23.45


ATOM
1626
N
SER
A
577
47.012
−1.983
19.818
1.00
21.78


ATOM
1627
CA
SER
A
577
45.759
−1.487
19.254
1.00
20.53


ATOM
1628
CB
SER
A
577
45.414
−2.221
17.957
1.00
20.28


ATOM
1629
OG
SER
A
577
46.319
−1.864
16.924
1.00
21.59


ATOM
1630
C
SER
A
577
44.676
−1.744
20.292
1.00
20.48


ATOM
1631
O
SER
A
577
44.709
−2.750
20.994
1.00
20.26


ATOM
1632
N
PRO
A
578
43.703
−0.833
20.408
1.00
20.02


ATOM
1633
CD
PRO
A
578
43.571
0.447
19.689
1.00
20.14


ATOM
1634
CA
PRO
A
578
42.627
−1.002
21.387
1.00
20.99


ATOM
1635
CB
PRO
A
578
41.949
0.369
21.391
1.00
19.33


ATOM
1636
CG
PRO
A
578
42.136
0.839
19.982
1.00
18.62


ATOM
1637
C
PRO
A
578
41.652
−2.147
21.108
1.00
22.22


ATOM
1638
O
PRO
A
578
41.073
−2.713
22.035
1.00
23.94


ATOM
1639
N
PHE
A
579
41.460
−2.490
19.841
1.00
23.82


ATOM
1640
CA
PHE
A
579
40.548
−3.575
19.482
1.00
23.84


ATOM
1641
CB
PHE
A
579
39.417
−3.028
18.605
1.00
22.19


ATOM
1642
CG
PHE
A
579
38.696
−1.868
19.227
1.00
20.44


ATOM
1643
CD1
PHE
A
579
38.963
−0.564
18.821
1.00
19.24


ATOM
1644
CD2
PHE
A
579
37.823
−2.072
20.292
1.00
20.80


ATOM
1645
CE1
PHE
A
579
38.378
0.520
19.471
1.00
19.55


ATOM
1646
CE2
PHE
A
579
37.234
−0.997
20.952
1.00
20.02


ATOM
1647
CZ
PHE
A
579
37.513
0.302
20.543
1.00
20.44


ATOM
1648
C
PHE
A
579
41.326
−4.685
18.779
1.00
25.48


ATOM
1649
O
PHE
A
579
42.094
−4.417
17.858
1.00
26.10


ATOM
1650
N
HIS
A
580
41.135
−5.921
19.241
1.00
27.92


ATOM
1651
CA
HIS
A
580
41.846
−7.087
18.706
1.00
30.44


ATOM
1652
CB
HIS
A
580
42.578
−7.857
19.817
1.00
32.29


ATOM
1653
CG
HIS
A
580
43.521
−7.032
20.626
1.00
35.99


ATOM
1654
CD2
HIS
A
580
44.836
−6.756
20.457
1.00
38.57


ATOM
1655
ND1
HIS
A
580
43.144
−6.407
21.795
1.00
38.02


ATOM
1656
CE1
HIS
A
580
44.188
−5.783
22.313
1.00
39.52


ATOM
1657
NE2
HIS
A
580
45.228
−5.979
21.521
1.00
40.35


ATOM
1658
C
HIS
A
580
40.956
−8.099
18.012
1.00
29.39


ATOM
1659
O
HIS
A
580
39.734
−8.046
18.105
1.00
30.42


ATOM
1660
N
GLY
A
581
41.606
−9.048
17.348
1.00
29.70


ATOM
1661
CA
GLY
A
581
40.906
−10.106
16.649
1.00
29.49


ATOM
1662
C
GLY
A
581
41.906
−10.980
15.923
1.00
29.16


ATOM
1663
O
GLY
A
581
42.903
−10.473
15.404
1.00
28.80


ATOM
1664
N
GLN
A
582
41.656
−12.287
15.888
1.00
29.65


ATOM
1665
CA
GLN
A
582
42.564
−13.201
15.204
1.00
28.88


ATOM
1666
CB
GLN
A
582
42.185
−14.656
15.476
1.00
29.32


ATOM
1667
CG
GLN
A
582
43.336
−15.615
15.225
1.00
28.13


ATOM
1668
CD
GLN
A
582
44.455
−15.441
16.242
1.00
28.61


ATOM
1669
OE1
GLN
A
582
45.635
−15.573
15.918
1.00
28.38


ATOM
1670
NE2
GLN
A
582
44.083
−15.157
17.484
1.00
27.38


ATOM
1671
C
GLN
A
582
42.480
−12.914
13.714
1.00
29.02


ATOM
1672
O
GLN
A
582
43.436
−13.126
12.972
1.00
29.72


ATOM
1673
N
ASP
A
583
41.316
−12.438
13.286
1.00
30.16


ATOM
1674
CA
ASP
A
583
41.082
−12.076
11.890
1.00
31.10


ATOM
1675
CB
ASP
A
583
40.417
−13.226
11.126
1.00
33.62


ATOM
1676
CG
ASP
A
583
39.171
−13.747
11.817
1.00
36.31


ATOM
1677
OD1
ASP
A
583
38.443
−12.944
12.442
1.00
37.13


ATOM
1678
OD2
ASP
A
583
38.912
−14.966
11.721
1.00
38.41


ATOM
1679
C
ASP
A
583
40.189
−10.838
11.852
1.00
30.92


ATOM
1680
O
ASP
A
583
39.749
−10.351
12.897
1.00
30.04


ATOM
1681
N
GLU
A
584
39.912
−10.332
10.656
1.00
31.45


ATOM
1682
CA
GLU
A
584
39.081
−9.139
10.516
1.00
31.84


ATOM
1683
CB
GLU
A
584
38.998
−8.728
9.046
1.00
33.47


ATOM
1684
CG
GLU
A
584
40.307
−8.168
8.514
1.00
38.25


ATOM
1685
CD
GLU
A
584
40.212
−7.736
7.068
1.00
41.02


ATOM
1686
OE1
GLU
A
584
39.265
−6.992
6.735
1.00
42.48


ATOM
1687
OE2
GLU
A
584
41.088
−8.130
6.267
1.00
42.67


ATOM
1688
C
GLU
A
584
37.679
−9.257
11.099
1.00
31.35


ATOM
1689
O
GLU
A
584
37.173
−8.309
11.701
1.00
30.38


ATOM
1690
N
GLU
A
585
37.046
−10.414
10.933
1.00
31.03


ATOM
1691
CA
GLU
A
585
35.703
−10.593
11.461
1.00
31.13


ATOM
1692
CB
GLU
A
585
35.152
−11.975
11.095
1.00
34.50


ATOM
1693
CG
GLU
A
585
35.192
−12.301
9.608
1.00
39.82


ATOM
1694
CD
GLU
A
585
34.189
−13.378
9.227
1.00
43.33


ATOM
1695
OE1
GLU
A
585
33.925
−14.278
10.059
1.00
44.73


ATOM
1696
OE2
GLU
A
585
33.670
−13.329
8.090
1.00
45.88


ATOM
1697
C
GLU
A
585
35.691
−10.431
12.976
1.00
29.88


ATOM
1698
O
GLU
A
585
34.793
−9.795
13.532
1.00
29.57


ATOM
1699
N
GLU
A
586
36.686
−11.005
13.646
1.00
28.10


ATOM
1700
CA
GLU
A
586
36.755
−10.907
15.098
1.00
27.35


ATOM
1701
CB
GLU
A
586
37.824
−11.856
15.641
1.00
30.54


ATOM
1702
CG
GLU
A
586
37.761
−12.054
17.149
1.00
34.93


ATOM
1703
CD
GLU
A
586
38.813
−13.029
17.644
1.00
37.75


ATOM
1704
OE1
GLU
A
586
38.971
−14.103
17.019
1.00
39.44


ATOM
1705
OE2
GLU
A
586
39.480
−12.722
18.655
1.00
39.69


ATOM
1706
C
GLU
A
586
37.083
−9.469
15.484
1.00
24.29


ATOM
1707
O
GLU
A
586
36.561
−8.936
16.465
1.00
22.10


ATOM
1708
N
LEU
A
587
37.955
−8.846
14.701
1.00
22.26


ATOM
1709
CA
LEU
A
587
38.333
−7.465
14.957
1.00
21.64


ATOM
1710
CB
LEU
A
587
39.364
−6.998
13.929
1.00
19.76


ATOM
1711
CG
LEU
A
587
39.666
−5.495
13.899
1.00
19.53


ATOM
1712
CD1
LEU
A
587
40.252
−5.050
15.231
1.00
18.49


ATOM
1713
CD2
LEU
A
587
40.636
−5.197
12.777
1.00
18.54


ATOM
1714
C
LEU
A
587
37.081
−6.592
14.872
1.00
22.22


ATOM
1715
O
LEU
A
587
36.829
−5.773
15.753
1.00
22.02


ATOM
1716
N
PHE
A
588
36.282
−6.785
13.825
1.00
22.51


ATOM
1717
CA
PHE
A
588
35.074
−5.979
13.658
1.00
23.33


ATOM
1718
CB
PHE
A
588
34.388
−6.282
12.321
1.00
22.37


ATOM
1719
CG
PHE
A
588
35.178
−5.828
11.115
1.00
23.33


ATOM
1720
CD1
PHE
A
588
36.218
−4.911
11.248
1.00
22.14


ATOM
1721
CD2
PHE
A
588
34.870
−6.309
9.841
1.00
25.16


ATOM
1722
CE1
PHE
A
588
36.946
−4.476
10.135
1.00
23.11


ATOM
1723
CE2
PHE
A
588
35.590
−5.881
8.715
1.00
24.51


ATOM
1724
CZ
PHE
A
588
36.631
−4.962
8.864
1.00
24.93


ATOM
1725
C
PHE
A
588
34.106
−6.164
14.803
1.00
23.40


ATOM
1726
O
PHE
A
588
33.482
−5.207
15.258
1.00
23.18


ATOM
1727
N
HIS
A
589
33.976
−7.396
15.277
1.00
25.00


ATOM
1728
CA
HIS
A
589
33.087
−7.654
16.399
1.00
26.65


ATOM
1729
CB
HIS
A
589
33.030
−9.154
16.700
1.00
29.36


ATOM
1730
CG
HIS
A
589
32.383
−9.478
18.011
1.00
33.33


ATOM
1731
CD2
HIS
A
589
31.135
−9.914
18.307
1.00
34.26


ATOM
1732
ND1
HIS
A
589
33.025
−9.306
19.220
1.00
33.60


ATOM
1733
CE1
HIS
A
589
32.200
−9.620
20.203
1.00
34.51


ATOM
1734
NE2
HIS
A
589
31.046
−9.991
19.676
1.00
34.62


ATOM
1735
C
HIS
A
589
33.608
−6.891
17.618
1.00
25.74


ATOM
1736
O
HIS
A
589
32.839
−6.302
18.377
1.00
25.34


ATOM
1737
N
SER
A
590
34.925
−6.895
17.789
1.00
26.30


ATOM
1738
CA
SER
A
590
35.557
−6.213
18.917
1.00
26.09


ATOM
1739
CB
SER
A
590
37.057
−6.513
18.927
1.00
26.34


ATOM
1740
OG
SER
A
590
37.707
−5.806
19.961
1.00
28.64


ATOM
1741
C
SER
A
590
35.325
−4.703
18.851
1.00
25.75


ATOM
1742
O
SER
A
590
35.034
−4.068
19.861
1.00
25.33


ATOM
1743
N
ILE
A
591
35.459
−4.134
17.657
1.00
25.04


ATOM
1744
CA
ILE
A
591
35.251
−2.704
17.461
1.00
25.15


ATOM
1745
CB
ILE
A
591
35.577
−2.299
15.997
1.00
23.60


ATOM
1746
CG2
ILE
A
591
35.082
−0.877
15.703
1.00
22.21


ATOM
1747
CG1
ILE
A
591
37.087
−2.411
15.764
1.00
22.39


ATOM
1748
CD1
ILE
A
591
37.506
−2.243
14.312
1.00
21.00


ATOM
1749
C
ILE
A
591
33.800
−2.342
17.785
1.00
27.12


ATOM
1750
O
ILE
A
591
33.523
−1.273
18.330
1.00
26.48


ATOM
1751
N
ARG
A
592
32.880
−3.246
17.465
1.00
29.01


ATOM
1752
CA
ARG
A
592
31.464
−3.006
17.719
1.00
32.00


ATOM
1753
CB
ARG
A
592
30.598
−3.892
16.809
1.00
32.52


ATOM
1754
CG
ARG
A
592
30.678
−3.588
15.318
1.00
33.53


ATOM
1755
CD
ARG
A
592
29.561
−4.307
14.566
1.00
35.57


ATOM
1756
NE
ARG
A
592
29.655
−5.767
14.656
1.00
36.97


ATOM
1757
CZ
ARG
A
592
30.300
−6.536
13.780
1.00
38.65


ATOM
1758
NH1
ARG
A
592
30.910
−5.990
12.735
1.00
38.86


ATOM
1759
NH2
ARG
A
592
30.336
−7.855
13.945
1.00
39.69


ATOM
1760
C
ARG
A
592
31.009
−3.231
19.165
1.00
33.46


ATOM
1761
O
ARG
A
592
30.113
−2.542
19.647
1.00
34.26


ATOM
1762
N
MET
A
593
31.628
−4.175
19.862
1.00
35.85


ATOM
1763
CA
MET
A
593
31.186
−4.503
21.217
1.00
38.64


ATOM
1764
CB
MET
A
593
30.766
−5.976
21.260
1.00
41.97


ATOM
1765
CG
MET
A
593
29.685
−6.360
20.272
1.00
46.33


ATOM
1766
SD
MET
A
593
28.092
−5.700
20.752
1.00
54.48


ATOM
1767
CE
MET
A
593
27.587
−6.935
21.934
1.00
52.43


ATOM
1768
C
MET
A
593
32.119
−4.258
22.398
1.00
38.21


ATOM
1769
O
MET
A
593
31.676
−3.839
23.465
1.00
38.65


ATOM
1770
N
ASP
A
594
33.405
−4.522
22.221
1.00
37.44


ATOM
1771
CA
ASP
A
594
34.343
−4.388
23.325
1.00
36.80


ATOM
1772
CB
ASP
A
594
35.613
−5.187
23.020
1.00
37.02


ATOM
1773
CG
ASP
A
594
35.321
−6.644
22.737
1.00
37.70


ATOM
1774
OD1
ASP
A
594
34.353
−7.175
23.326
1.00
38.82


ATOM
1775
OD2
ASP
A
594
36.064
−7.257
21.941
1.00
38.55


ATOM
1776
C
ASP
A
594
34.751
−3.014
23.834
1.00
35.81


ATOM
1777
O
ASP
A
594
34.643
−1.993
23.153
1.00
34.95


ATOM
1778
N
ASN
A
595
35.218
−3.023
25.074
1.00
34.85


ATOM
1779
CA
ASN
A
595
35.714
−1.834
25.731
1.00
33.81


ATOM
1780
CB
ASN
A
595
35.162
−1.740
27.151
1.00
36.16


ATOM
1781
CG
ASN
A
595
33.818
−1.049
27.203
1.00
38.48


ATOM
1782
OD1
ASN
A
595
33.106
−1.134
28.204
1.00
41.34


ATOM
1783
ND2
ASN
A
595
33.468
−0.346
26.129
1.00
39.15


ATOM
1784
C
ASN
A
595
37.213
−2.033
25.766
1.00
31.92


ATOM
1785
O
ASN
A
595
37.692
−3.071
26.216
1.00
31.53


ATOM
1786
N
PRO
A
596
37.978
−1.056
25.260
1.00
30.60


ATOM
1787
CD
PRO
A
596
37.546
0.176
24.583
1.00
29.67


ATOM
1788
CA
PRO
A
596
39.440
−1.169
25.256
1.00
29.64


ATOM
1789
CB
PRO
A
596
39.883
0.132
24.595
1.00
29.35


ATOM
1790
CG
PRO
A
596
38.723
0.471
23.707
1.00
30.33


ATOM
1791
C
PRO
A
596
39.994
−1.308
26.670
1.00
28.01


ATOM
1792
O
PRO
A
596
39.380
−0.863
27.636
1.00
28.24


ATOM
1793
N
PHE
A
597
41.157
−1.935
26.788
1.00
27.78


ATOM
1794
CA
PHE
A
597
41.792
−2.106
28.088
1.00
26.60


ATOM
1795
CB
PHE
A
597
42.682
−3.351
28.086
1.00
27.31


ATOM
1796
CG
PHE
A
597
43.592
−3.446
29.280
1.00
30.04


ATOM
1797
CD1
PHE
A
597
43.094
−3.809
30.525
1.00
29.77


ATOM
1798
CD2
PHE
A
597
44.953
−3.160
29.159
1.00
29.89


ATOM
1799
CE1
PHE
A
597
43.935
−3.887
31.636
1.00
30.89


ATOM
1800
CE2
PHE
A
597
45.801
−3.235
30.265
1.00
31.09


ATOM
1801
CZ
PHE
A
597
45.291
−3.599
31.503
1.00
30.00


ATOM
1802
C
PHE
A
597
42.652
−0.886
28.392
1.00
25.52


ATOM
1803
O
PHE
A
597
43.442
−0.455
27.554
1.00
25.53


ATOM
1804
N
TYR
A
598
42.494
−0.327
29.585
1.00
24.22


ATOM
1805
CA
TYR
A
598
43.291
0.817
29.991
1.00
23.67


ATOM
1806
CB
TYR
A
598
42.394
1.995
30.378
1.00
22.81


ATOM
1807
CG
TYR
A
598
41.446
2.445
29.287
1.00
22.42


ATOM
1808
CD1
TYR
A
598
40.103
2.078
29.312
1.00
22.51


ATOM
1809
CE1
TYR
A
598
39.216
2.507
28.322
1.00
23.12


ATOM
1810
CD2
TYR
A
598
41.889
3.254
28.236
1.00
22.09


ATOM
1811
CE2
TYR
A
598
41.011
3.690
27.237
1.00
22.62


ATOM
1812
CZ
TYR
A
598
39.675
3.312
27.290
1.00
22.97


ATOM
1813
OH
TYR
A
598
38.797
3.745
26.328
1.00
22.74


ATOM
1814
C
TYR
A
598
44.157
0.412
31.189
1.00
24.15


ATOM
1815
O
TYR
A
598
43.636
0.028
32.234
1.00
23.99


ATOM
1816
N
PRO
A
599
45.491
0.474
31.040
1.00
23.70


ATOM
1817
CD
PRO
A
599
46.192
0.727
29.769
1.00
23.44


ATOM
1818
CA
PRO
A
599
46.445
0.122
32.102
1.00
24.35


ATOM
1819
CB
PRO
A
599
47.805
0.292
31.426
1.00
23.90


ATOM
1820
CG
PRO
A
599
47.504
0.014
29.983
1.00
25.50


ATOM
1821
C
PRO
A
599
46.311
1.039
33.315
1.00
24.95


ATOM
1822
O
PRO
A
599
45.901
2.195
33.187
1.00
24.15


ATOM
1823
N
ARG
A
600
46.672
0.527
34.490
1.00
26.05


ATOM
1824
CA
ARG
A
600
46.588
1.318
35.713
1.00
25.85


ATOM
1825
CB
ARG
A
600
46.892
0.455
36.942
1.00
29.45


ATOM
1826
CG
ARG
A
600
45.769
−0.484
37.347
1.00
34.03


ATOM
1827
CD
ARG
A
600
45.998
−1.898
36.832
1.00
39.90


ATOM
1828
NE
ARG
A
600
46.299
−2.836
37.917
1.00
44.39


ATOM
1829
CZ
ARG
A
600
46.470
−4.146
37.751
1.00
46.14


ATOM
1830
NH1
ARG
A
600
46.372
−4.682
36.538
1.00
45.41


ATOM
1831
NH2
ARG
A
600
46.743
−4.923
38.797
1.00
46.69


ATOM
1832
C
ARG
A
600
47.513
2.529
35.708
1.00
23.47


ATOM
1833
O
ARG
A
600
47.302
3.470
36.463
1.00
23.50


ATOM
1834
N
TRP
A
601
48.537
2.512
34.862
1.00
21.86


ATOM
1835
CA
TRP
A
601
49.460
3.638
34.809
1.00
22.35


ATOM
1836
CB
TRP
A
601
50.870
3.169
34.445
1.00
20.25


ATOM
1837
CG
TRP
A
601
50.933
2.223
33.283
1.00
22.07


ATOM
1838
CD2
TRP
A
601
50.945
2.569
31.890
1.00
20.12


ATOM
1839
CE2
TRP
A
601
51.049
1.362
31.159
1.00
20.17


ATOM
1840
CE3
TRP
A
601
50.880
3.782
31.189
1.00
20.56


ATOM
1841
CD1
TRP
A
601
51.019
0.857
33.339
1.00
21.89


ATOM
1842
NE1
TRP
A
601
51.091
0.335
32.065
1.00
21.32


ATOM
1843
CZ2
TRP
A
601
51.091
1.333
29.758
1.00
20.08


ATOM
1844
CZ3
TRP
A
601
50.922
3.754
29.788
1.00
19.61


ATOM
1845
CH2
TRP
A
601
51.027
2.535
29.093
1.00
17.82


ATOM
1846
C
TRP
A
601
49.035
4.739
33.846
1.00
23.13


ATOM
1847
O
TRP
A
601
49.686
5.778
33.770
1.00
24.05


ATOM
1848
N
LEU
A
602
47.956
4.516
33.102
1.00
22.98


ATOM
1849
CA
LEU
A
602
47.487
5.526
32.162
1.00
22.13


ATOM
1850
CB
LEU
A
602
46.467
4.934
31.188
1.00
22.04


ATOM
1851
CG
LEU
A
602
45.941
5.879
30.097
1.00
21.71


ATOM
1852
CD1
LEU
A
602
47.102
6.406
29.268
1.00
20.07


ATOM
1853
CD2
LEU
A
602
44.955
5.138
29.201
1.00
20.91


ATOM
1854
C
LEU
A
602
46.850
6.671
32.931
1.00
21.89


ATOM
1855
O
LEU
A
602
45.929
6.464
33.716
1.00
21.33


ATOM
1856
N
GLU
A
603
47.350
7.879
32.704
1.00
22.45


ATOM
1857
CA
GLU
A
603
46.832
9.062
33.378
1.00
25.25


ATOM
1858
CB
GLU
A
603
47.572
10.302
32.870
1.00
27.46


ATOM
1859
CG
GLU
A
603
47.469
11.519
33.775
1.00
32.35


ATOM
1860
CD
GLU
A
603
48.100
11.301
35.152
1.00
34.52


ATOM
1861
OE1
GLU
A
603
49.335
11.121
35.240
1.00
34.96


ATOM
1862
OE2
GLU
A
603
47.352
11.309
36.151
1.00
37.44


ATOM
1863
C
GLU
A
603
45.318
9.215
33.168
1.00
25.68


ATOM
1864
O
GLU
A
603
44.787
8.914
32.092
1.00
23.45


ATOM
1865
N
LYS
A
604
44.636
9.684
34.207
1.00
26.33


ATOM
1866
CA
LYS
A
604
43.192
9.870
34.178
1.00
28.53


ATOM
1867
CB
LYS
A
604
42.709
10.438
35.515
1.00
30.83


ATOM
1868
CG
LYS
A
604
41.958
9.436
36.370
1.00
34.84


ATOM
1869
CD
LYS
A
604
42.820
8.216
36.660
1.00
38.17


ATOM
1870
CE
LYS
A
604
42.058
7.169
37.450
1.00
39.22


ATOM
1871
NZ
LYS
A
604
42.011
5.874
36.709
1.00
42.12


ATOM
1872
C
LYS
A
604
42.645
10.742
33.055
1.00
27.71


ATOM
1873
O
LYS
A
604
41.671
10.373
32.405
1.00
27.04


ATOM
1874
N
GLU
A
605
43.246
11.902
32.817
1.00
27.80


ATOM
1875
CA
GLU
A
605
42.713
12.752
31.766
1.00
28.43


ATOM
1876
CB
GLU
A
605
43.309
14.174
31.858
1.00
31.54


ATOM
1877
CG
GLU
A
605
43.354
14.810
33.294
1.00
38.39


ATOM
1878
CD
GLU
A
605
41.989
14.959
34.018
1.00
43.04


ATOM
1879
OE1
GLU
A
605
40.929
14.566
33.460
1.00
45.70


ATOM
1880
OE2
GLU
A
605
41.989
15.476
35.168
1.00
45.62


ATOM
1881
C
GLU
A
605
42.937
12.113
30.372
1.00
26.18


ATOM
1882
O
GLU
A
605
42.181
12.412
29.427
1.00
24.76


ATOM
1883
N
ALA
A
606
43.935
11.239
30.229
1.00
23.82


ATOM
1884
CA
ALA
A
606
44.161
10.570
28.933
1.00
22.57


ATOM
1885
CB
ALA
A
606
45.578
9.939
28.874
1.00
21.71


ATOM
1886
C
ALA
A
606
43.106
9.484
28.740
1.00
22.43


ATOM
1887
O
ALA
A
606
42.544
9.350
27.655
1.00
20.21


ATOM
1888
N
LYS
A
607
42.824
8.734
29.807
1.00
21.01


ATOM
1889
CA
LYS
A
607
41.809
7.692
29.741
1.00
21.08


ATOM
1890
CB
LYS
A
607
41.675
6.964
31.083
1.00
21.77


ATOM
1891
CG
LYS
A
607
40.450
6.049
31.133
1.00
24.04


ATOM
1892
CD
LYS
A
607
40.400
5.159
32.366
1.00
26.01


ATOM
1893
CE
LYS
A
607
39.151
4.277
32.318
1.00
28.75


ATOM
1894
NZ
LYS
A
607
39.036
3.355
33.483
1.00
30.88


ATOM
1895
C
LYS
A
607
40.472
8.333
29.403
1.00
20.56


ATOM
1896
O
LYS
A
607
39.698
7.802
28.597
1.00
18.86


ATOM
1897
N
ASP
A
608
40.213
9.476
30.031
1.00
18.92


ATOM
1898
CA
ASP
A
608
38.963
10.190
29.822
1.00
19.51


ATOM
1899
CB
ASP
A
608
38.865
11.381
30.784
1.00
20.44


ATOM
1900
CG
ASP
A
608
37.577
12.168
30.611
1.00
23.54


ATOM
1901
OD1
ASP
A
608
37.527
13.064
29.740
1.00
26.83


ATOM
1902
OD2
ASP
A
608
36.603
11.884
31.341
1.00
24.81


ATOM
1903
C
ASP
A
608
38.803
10.664
28.381
1.00
18.24


ATOM
1904
O
ASP
A
608
37.700
10.629
27.831
1.00
17.10


ATOM
1905
N
LEU
A
609
39.893
11.114
27.771
1.00
16.92


ATOM
1906
CA
LEU
A
609
39.828
11.581
26.392
1.00
17.82


ATOM
1907
CB
LEU
A
609
41.163
12.192
25.963
1.00
17.75


ATOM
1908
CG
LEU
A
609
41.279
12.576
24.481
1.00
18.80


ATOM
1909
CD1
LEU
A
609
40.140
13.512
24.080
1.00
16.89


ATOM
1910
CD2
LEU
A
609
42.633
13.233
24.240
1.00
17.44


ATOM
1911
C
LEU
A
609
39.483
10.402
25.490
1.00
17.65


ATOM
1912
O
LEU
A
609
38.585
10.491
24.650
1.00
16.34


ATOM
1913
N
LEU
A
610
40.190
9.291
25.684
1.00
17.49


ATOM
1914
CA
LEU
A
610
39.964
8.088
24.887
1.00
17.58


ATOM
1915
CB
LEU
A
610
40.971
7.000
25.282
1.00
16.75


ATOM
1916
CG
LEU
A
610
42.401
7.321
24.844
1.00
18.71


ATOM
1917
CD1
LEU
A
610
43.379
6.313
25.414
1.00
19.41


ATOM
1918
CD2
LEU
A
610
42.458
7.333
23.315
1.00
16.53


ATOM
1919
C
LEU
A
610
38.538
7.557
25.018
1.00
17.89


ATOM
1920
O
LEU
A
610
37.920
7.158
24.024
1.00
18.16


ATOM
1921
N
VAL
A
611
38.015
7.561
26.241
1.00
18.35


ATOM
1922
CA
VAL
A
611
36.663
7.078
26.503
1.00
18.91


ATOM
1923
CB
VAL
A
611
36.338
7.109
28.022
1.00
19.47


ATOM
1924
CG1
VAL
A
611
34.865
6.801
28.255
1.00
20.48


ATOM
1925
CG2
VAL
A
611
37.193
6.089
28.762
1.00
18.53


ATOM
1926
C
VAL
A
611
35.648
7.937
25.751
1.00
19.87


ATOM
1927
O
VAL
A
611
34.666
7.428
25.195
1.00
20.48


ATOM
1928
N
LYS
A
612
35.887
9.242
25.725
1.00
20.16


ATOM
1929
CA
LYS
A
612
34.991
10.153
25.024
1.00
20.51


ATOM
1930
CB
LYS
A
612
35.268
11.599
25.439
1.00
22.37


ATOM
1931
CG
LYS
A
612
34.768
11.960
26.831
1.00
23.80


ATOM
1932
CD
LYS
A
612
35.319
13.315
27.235
1.00
25.64


ATOM
1933
CE
LYS
A
612
34.726
13.822
28.552
1.00
27.36


ATOM
1934
NZ
LYS
A
612
34.451
12.718
29.518
1.00
29.33


ATOM
1935
C
LYS
A
612
35.143
10.017
23.506
1.00
19.09


ATOM
1936
O
LYS
A
612
34.246
10.373
22.751
1.00
18.65


ATOM
1937
N
LEU
A
613
36.287
9.517
23.060
1.00
18.34


ATOM
1938
CA
LEU
A
613
36.505
9.332
21.635
1.00
18.28


ATOM
1939
CB
LEU
A
613
37.996
9.380
21.303
1.00
16.91


ATOM
1940
CG
LEU
A
613
38.628
10.773
21.333
1.00
18.21


ATOM
1941
CD1
LEU
A
613
40.147
10.653
21.287
1.00
17.29


ATOM
1942
CD2
LEU
A
613
38.089
11.593
20.155
1.00
16.95


ATOM
1943
C
LEU
A
613
35.929
7.996
21.189
1.00
19.04


ATOM
1944
O
LEU
A
613
35.481
7.863
20.052
1.00
18.79


ATOM
1945
N
PHE
A
614
35.931
7.009
22.083
1.00
18.64


ATOM
1946
CA
PHE
A
614
35.421
5.686
21.727
1.00
20.32


ATOM
1947
CB
PHE
A
614
36.187
4.588
22.478
1.00
18.01


ATOM
1948
CG
PHE
A
614
37.619
4.431
22.029
1.00
18.67


ATOM
1949
CD1
PHE
A
614
37.937
4.415
20.671
1.00
15.87


ATOM
1950
CD2
PHE
A
614
38.648
4.286
22.962
1.00
18.49


ATOM
1951
CE1
PHE
A
614
39.253
4.255
20.246
1.00
15.71


ATOM
1952
CE2
PHE
A
614
39.976
4.123
22.549
1.00
17.66


ATOM
1953
CZ
PHE
A
614
40.279
4.107
21.189
1.00
15.59


ATOM
1954
C
PHE
A
614
33.921
5.498
21.927
1.00
21.76


ATOM
1955
O
PHE
A
614
33.443
4.384
22.132
1.00
23.60


ATOM
1956
N
VAL
A
615
33.177
6.591
21.870
1.00
23.03


ATOM
1957
CA
VAL
A
615
31.732
6.517
21.998
1.00
24.19


ATOM
1958
CB
VAL
A
615
31.138
7.908
22.325
1.00
23.89


ATOM
1959
CG1
VAL
A
615
29.638
7.920
22.070
1.00
23.25


ATOM
1960
CG2
VAL
A
615
31.424
8.253
23.789
1.00
25.32


ATOM
1961
C
VAL
A
615
31.220
6.017
20.643
1.00
24.80


ATOM
1962
O
VAL
A
615
31.557
6.582
19.602
1.00
23.38


ATOM
1963
N
ARG
A
616
30.436
4.942
20.666
1.00
26.89


ATOM
1964
CA
ARG
A
616
29.880
4.344
19.449
1.00
29.04


ATOM
1965
CB
ARG
A
616
29.056
3.103
19.793
1.00
31.64


ATOM
1966
CG
ARG
A
616
29.785
1.778
19.607
1.00
34.39


ATOM
1967
CD
ARG
A
616
30.963
1.656
20.540
1.00
36.74


ATOM
1968
NE
ARG
A
616
31.607
0.346
20.450
1.00
39.00


ATOM
1969
CZ
ARG
A
616
32.574
−0.060
21.272
1.00
39.50


ATOM
1970
NH1
ARG
A
616
33.001
0.742
22.241
1.00
40.12


ATOM
1971
NH2
ARG
A
616
33.123
−1.258
21.124
1.00
39.14


ATOM
1972
C
ARG
A
616
29.012
5.304
18.642
1.00
28.72


ATOM
1973
O
ARG
A
616
29.221
5.472
17.443
1.00
30.06


ATOM
1974
N
GLU
A
617
28.024
5.910
19.294
1.00
28.29


ATOM
1975
CA
GLU
A
617
27.141
6.860
18.628
1.00
27.91


ATOM
1976
CB
GLU
A
617
26.036
7.314
19.586
1.00
29.77


ATOM
1977
CG
GLU
A
617
25.340
8.598
19.163
1.00
34.82


ATOM
1978
CD
GLU
A
617
24.729
8.501
17.776
1.00
38.01


ATOM
1979
OE1
GLU
A
617
24.977
9.408
16.944
1.00
38.60


ATOM
1980
OE2
GLU
A
617
23.999
7.518
17.520
1.00
39.63


ATOM
1981
C
GLU
A
617
27.973
8.058
18.177
1.00
25.97


ATOM
1982
O
GLU
A
617
28.435
8.848
18.994
1.00
24.63


ATOM
1983
N
PRO
A
618
28.178
8.204
16.858
1.00
25.94


ATOM
1984
CD
PRO
A
618
27.663
7.357
15.769
1.00
24.89


ATOM
1985
CA
PRO
A
618
28.970
9.317
16.324
1.00
25.61


ATOM
1986
CB
PRO
A
618
28.913
9.089
14.810
1.00
24.66


ATOM
1987
CG
PRO
A
618
27.646
8.316
14.614
1.00
24.37


ATOM
1988
C
PRO
A
618
28.534
10.728
16.726
1.00
26.29


ATOM
1989
O
PRO
A
618
29.377
11.608
16.895
1.00
25.62


ATOM
1990
N
GLU
A
619
27.235
10.948
16.893
1.00
26.10


ATOM
1991
CA
GLU
A
619
26.761
12.276
17.259
1.00
26.97


ATOM
1992
CB
GLU
A
619
25.254
12.401
16.990
1.00
29.74


ATOM
1993
CG
GLU
A
619
24.859
11.991
15.572
1.00
35.15


ATOM
1994
CD
GLU
A
619
23.476
12.472
15.170
1.00
39.06


ATOM
1995
OE1
GLU
A
619
22.501
12.210
15.915
1.00
40.39


ATOM
1996
OE2
GLU
A
619
23.365
13.109
14.097
1.00
40.52


ATOM
1997
C
GLU
A
619
27.075
12.652
18.704
1.00
25.65


ATOM
1998
O
GLU
A
619
26.899
13.798
19.097
1.00
25.78


ATOM
1999
N
LYS
A
620
27.542
11.696
19.498
1.00
24.88


ATOM
2000
CA
LYS
A
620
27.881
11.980
20.895
1.00
24.66


ATOM
2001
CB
LYS
A
620
27.165
11.007
21.835
1.00
25.75


ATOM
2002
CG
LYS
A
620
25.642
11.143
21.881
1.00
29.43


ATOM
2003
CD
LYS
A
620
25.042
10.075
22.802
1.00
32.34


ATOM
2004
CE
LYS
A
620
23.525
10.167
22.864
1.00
36.50


ATOM
2005
NZ
LYS
A
620
22.929
9.083
23.703
1.00
39.45


ATOM
2006
C
LYS
A
620
29.388
11.867
21.123
1.00
22.83


ATOM
2007
O
LYS
A
620
29.856
11.904
22.259
1.00
21.86


ATOM
2008
N
ARG
A
621
30.138
11.723
20.034
1.00
21.02


ATOM
2009
CA
ARG
A
621
31.584
11.570
20.105
1.00
18.14


ATOM
2010
CB
ARG
A
621
32.073
10.749
18.911
1.00
16.86


ATOM
2011
CG
ARG
A
621
33.562
10.398
18.932
1.00
17.14


ATOM
2012
CD
ARG
A
621
33.927
9.530
17.723
1.00
16.79


ATOM
2013
NE
ARG
A
621
33.102
8.324
17.686
1.00
16.88


ATOM
2014
CZ
ARG
A
621
32.660
7.748
16.569
1.00
16.19


ATOM
2015
NH1
ARG
A
621
32.972
8.259
15.379
1.00
14.37


ATOM
2016
NH2
ARG
A
621
31.870
6.685
16.644
1.00
12.08


ATOM
2017
C
ARG
A
621
32.317
12.903
20.139
1.00
18.18


ATOM
2018
O
ARG
A
621
32.048
13.792
19.326
1.00
17.33


ATOM
2019
N
LEU
A
622
33.243
13.036
21.087
1.00
17.53


ATOM
2020
CA
LEU
A
622
34.033
14.254
21.209
1.00
18.54


ATOM
2021
CB
LEU
A
622
35.085
14.099
22.321
1.00
19.59


ATOM
2022
CG
LEU
A
622
35.931
15.323
22.711
1.00
20.18


ATOM
2023
CD1
LEU
A
622
35.034
16.518
23.061
1.00
20.18


ATOM
2024
CD2
LEU
A
622
36.807
14.962
23.903
1.00
20.55


ATOM
2025
C
LEU
A
622
34.694
14.443
19.847
1.00
17.81


ATOM
2026
O
LEU
A
622
35.144
13.478
19.228
1.00
17.38


ATOM
2027
N
GLY
A
623
34.743
15.680
19.377
1.00
17.75


ATOM
2028
CA
GLY
A
623
35.309
15.948
18.066
1.00
18.80


ATOM
2029
C
GLY
A
623
34.144
16.258
17.139
1.00
20.02


ATOM
2030
O
GLY
A
623
34.220
17.140
16.286
1.00
20.81


ATOM
2031
N
VAL
A
624
33.058
15.512
17.309
1.00
21.39


ATOM
2032
CA
VAL
A
624
31.837
15.714
16.536
1.00
22.85


ATOM
2033
CB
VAL
A
624
31.053
14.392
16.373
1.00
22.84


ATOM
2034
CG1
VAL
A
624
29.697
14.662
15.726
1.00
22.60


ATOM
2035
CG2
VAL
A
624
31.866
13.402
15.545
1.00
21.63


ATOM
2036
C
VAL
A
624
31.014
16.673
17.391
1.00
25.48


ATOM
2037
O
VAL
A
624
30.473
17.668
16.911
1.00
27.26


ATOM
2038
N
ARG
A
625
30.947
16.348
18.677
1.00
27.42


ATOM
2039
CA
ARG
A
625
30.232
17.133
19.663
1.00
30.03


ATOM
2040
CB
ARG
A
625
29.289
16.241
20.467
1.00
33.23


ATOM
2041
CG
ARG
A
625
28.593
17.086
21.482
1.00
39.62


ATOM
2042
CD
ARG
A
625
27.798
16.404
22.568
1.00
43.58


ATOM
2043
NE
ARG
A
625
26.835
17.422
22.942
1.00
47.75


ATOM
2044
CZ
ARG
A
625
27.128
18.510
23.641
1.00
49.41


ATOM
2045
NH1
ARG
A
625
28.356
18.723
24.085
1.00
50.35


ATOM
2046
NH2
ARG
A
625
26.201
19.440
23.826
1.00
50.78


ATOM
2047
C
ARG
A
625
31.248
17.760
20.633
1.00
30.21


ATOM
2048
O
ARG
A
625
32.221
17.108
21.012
1.00
30.87


ATOM
2049
N
GLY
A
626
31.022
19.007
21.044
1.00
29.54


ATOM
2050
CA
GLY
A
626
31.937
19.653
21.972
1.00
27.47


ATOM
2051
C
GLY
A
626
33.178
20.236
21.319
1.00
26.92


ATOM
2052
O
GLY
A
626
33.237
20.367
20.094
1.00
26.89


ATOM
2053
N
ASP
A
627
34.172
20.580
22.135
1.00
25.86


ATOM
2054
CA
ASP
A
627
35.424
21.161
21.646
1.00
24.96


ATOM
2055
CB
ASP
A
627
35.552
22.605
22.138
1.00
26.17


ATOM
2056
CG
ASP
A
627
36.691
23.350
21.472
1.00
27.16


ATOM
2057
OD1
ASP
A
627
37.589
22.693
20.902
1.00
28.82


ATOM
2058
OD2
ASP
A
627
36.695
24.597
21.527
1.00
28.40


ATOM
2059
C
ASP
A
627
36.593
20.339
22.179
1.00
23.74


ATOM
2060
O
ASP
A
627
37.027
20.531
23.317
1.00
24.37


ATOM
2061
N
ILE
A
628
37.113
19.431
21.355
1.00
22.06


ATOM
2062
CA
ILE
A
628
38.211
18.570
21.773
1.00
19.76


ATOM
2063
CB
ILE
A
628
38.633
17.593
20.646
1.00
19.34


ATOM
2064
CG2
ILE
A
628
39.300
18.358
19.500
1.00
16.53


ATOM
2065
CG1
ILE
A
628
39.591
16.538
21.212
1.00
18.57


ATOM
2066
CD1
ILE
A
628
39.876
15.380
20.255
1.00
20.57


ATOM
2067
C
ILE
A
628
39.442
19.335
22.247
1.00
20.24


ATOM
2068
O
ILE
A
628
40.214
18.821
23.056
1.00
19.32


ATOM
2069
N
ARG
A
629
39.623
20.558
21.754
1.00
20.13


ATOM
2070
CA
ARG
A
629
40.776
21.364
22.149
1.00
21.20


ATOM
2071
CB
ARG
A
629
40.873
22.625
21.302
1.00
23.00


ATOM
2072
CG
ARG
A
629
41.103
22.422
19.813
1.00
26.51


ATOM
2073
CD
ARG
A
629
41.067
23.790
19.146
1.00
28.34


ATOM
2074
NE
ARG
A
629
40.993
23.709
17.695
1.00
32.08


ATOM
2075
CZ
ARG
A
629
40.515
24.679
16.924
1.00
31.10


ATOM
2076
NH1
ARG
A
629
40.067
25.802
17.472
1.00
32.62


ATOM
2077
NH2
ARG
A
629
40.475
24.520
15.609
1.00
31.06


ATOM
2078
C
ARG
A
629
40.715
21.780
23.615
1.00
21.03


ATOM
2079
O
ARG
A
629
41.749
22.024
24.235
1.00
20.90


ATOM
2080
N
GLN
A
630
39.500
21.876
24.153
1.00
21.32


ATOM
2081
CA
GLN
A
630
39.297
22.269
25.542
1.00
21.75


ATOM
2082
CB
GLN
A
630
37.947
22.995
25.695
1.00
24.51


ATOM
2083
CG
GLN
A
630
37.898
24.386
25.041
1.00
28.07


ATOM
2084
CD
GLN
A
630
36.482
24.948
24.936
1.00
32.22


ATOM
2085
OE1
GLN
A
630
36.075
25.432
23.875
1.00
35.05


ATOM
2086
NE2
GLN
A
630
35.728
24.892
26.033
1.00
34.16


ATOM
2087
C
GLN
A
630
39.364
21.092
26.518
1.00
21.79


ATOM
2088
O
GLN
A
630
39.085
21.256
27.708
1.00
20.81


ATOM
2089
N
HIS
A
631
39.732
19.905
26.038
1.00
20.56


ATOM
2090
CA
HIS
A
631
39.820
18.770
26.949
1.00
20.96


ATOM
2091
CB
HIS
A
631
39.964
17.443
26.186
1.00
20.32


ATOM
2092
CG
HIS
A
631
39.883
16.235
27.071
1.00
19.91


ATOM
2093
CD2
HIS
A
631
38.844
15.419
27.373
1.00
19.57


ATOM
2094
ND1
HIS
A
631
40.940
15.805
27.843
1.00
18.48


ATOM
2095
CE1
HIS
A
631
40.557
14.781
28.585
1.00
18.06


ATOM
2096
NE2
HIS
A
631
39.288
14.527
28.319
1.00
18.09


ATOM
2097
C
HIS
A
631
41.019
18.985
27.873
1.00
21.47


ATOM
2098
O
HIS
A
631
42.080
19.429
27.433
1.00
20.95


ATOM
2099
N
PRO
A
632
40.859
18.682
29.172
1.00
21.77


ATOM
2100
CD
PRO
A
632
39.638
18.111
29.774
1.00
22.35


ATOM
2101
CA
PRO
A
632
41.908
18.835
30.187
1.00
22.53


ATOM
2102
CB
PRO
A
632
41.333
18.083
31.387
1.00
22.88


ATOM
2103
CG
PRO
A
632
39.876
18.334
31.258
1.00
22.65


ATOM
2104
C
PRO
A
632
43.290
18.312
29.788
1.00
22.97


ATOM
2105
O
PRO
A
632
44.312
18.880
30.181
1.00
22.81


ATOM
2106
N
LEU
A
633
43.322
17.231
29.014
1.00
22.42


ATOM
2107
CA
LEU
A
633
44.591
16.654
28.580
1.00
22.24


ATOM
2108
CB
LEU
A
633
44.351
15.454
27.657
1.00
22.84


ATOM
2109
CG
LEU
A
633
45.628
14.711
27.245
1.00
24.28


ATOM
2110
CD1
LEU
A
633
46.275
14.108
28.488
1.00
23.65


ATOM
2111
CD2
LEU
A
633
45.308
13.618
26.233
1.00
24.13


ATOM
2112
C
LEU
A
633
45.464
17.665
27.846
1.00
22.12


ATOM
2113
O
LEU
A
633
46.691
17.586
27.898
1.00
21.96


ATOM
2114
N
PHE
A
634
44.828
18.612
27.164
1.00
21.41


ATOM
2115
CA
PHE
A
634
45.546
19.627
26.393
1.00
22.24


ATOM
2116
CB
PHE
A
634
44.846
19.827
25.040
1.00
19.99


ATOM
2117
CG
PHE
A
634
44.737
18.568
24.216
1.00
19.23


ATOM
2118
CD1
PHE
A
634
45.879
17.954
23.711
1.00
17.11


ATOM
2119
CD2
PHE
A
634
43.497
17.998
23.945
1.00
17.62


ATOM
2120
CE1
PHE
A
634
45.794
16.788
22.944
1.00
17.67


ATOM
2121
CE2
PHE
A
634
43.397
16.828
23.179
1.00
18.20


ATOM
2122
CZ
PHE
A
634
44.553
16.223
22.678
1.00
15.92


ATOM
2123
C
PHE
A
634
45.627
20.979
27.109
1.00
24.10


ATOM
2124
O
PHE
A
634
45.938
21.999
26.488
1.00
22.28


ATOM
2125
N
ARG
A
635
45.374
20.986
28.413
1.00
25.98


ATOM
2126
CA
ARG
A
635
45.362
22.238
29.156
1.00
29.34


ATOM
2127
CB
ARG
A
635
45.081
21.963
30.639
1.00
32.29


ATOM
2128
CG
ARG
A
635
46.271
21.515
31.461
1.00
37.47


ATOM
2129
CD
ARG
A
635
45.774
21.019
32.786
1.00
42.18


ATOM
2130
NE
ARG
A
635
45.403
19.616
32.675
1.00
47.46


ATOM
2131
CZ
ARG
A
635
45.616
18.713
33.627
1.00
49.68


ATOM
2132
NH1
ARG
A
635
46.208
19.074
34.752
1.00
51.44


ATOM
2133
NH2
ARG
A
635
45.200
17.449
33.486
1.00
51.05


ATOM
2134
C
ARG
A
635
46.574
23.154
28.996
1.00
29.35


ATOM
2135
O
ARG
A
635
46.422
24.370
28.968
1.00
29.93


ATOM
2136
N
GLU
A
636
47.767
22.590
28.872
1.00
29.88


ATOM
2137
CA
GLU
A
636
48.954
23.416
28.720
1.00
31.27


ATOM
2138
CB
GLU
A
636
50.173
22.690
29.285
1.00
34.01


ATOM
2139
CG
GLU
A
636
50.127
22.511
30.785
1.00
38.90


ATOM
2140
CD
GLU
A
636
51.453
22.058
31.342
1.00
43.00


ATOM
2141
OE1
GLU
A
636
51.890
20.938
31.001
1.00
45.28


ATOM
2142
OE2
GLU
A
636
52.067
22.824
32.117
1.00
44.88


ATOM
2143
C
GLU
A
636
49.256
23.859
27.289
1.00
30.50


ATOM
2144
O
GLU
A
636
50.222
24.581
27.051
1.00
30.25


ATOM
2145
N
ILE
A
637
48.434
23.446
26.333
1.00
28.70


ATOM
2146
CA
ILE
A
637
48.689
23.828
24.954
1.00
26.92


ATOM
2147
CB
ILE
A
637
48.282
22.695
23.977
1.00
27.47


ATOM
2148
CG2
ILE
A
637
48.187
23.232
22.550
1.00
26.79


ATOM
2149
CG1
ILE
A
637
49.301
21.553
24.075
1.00
28.20


ATOM
2150
CD1
ILE
A
637
49.044
20.425
23.133
1.00
30.14


ATOM
2151
C
ILE
A
637
48.031
25.119
24.482
1.00
25.43


ATOM
2152
O
ILE
A
637
46.837
25.338
24.670
1.00
24.21


ATOM
2153
N
ASN
A
638
48.838
25.981
23.876
1.00
24.21


ATOM
2154
CA
ASN
A
638
48.337
27.217
23.301
1.00
23.39


ATOM
2155
CB
ASN
A
638
49.351
28.352
23.455
1.00
24.07


ATOM
2156
CG
ASN
A
638
48.853
29.653
22.853
1.00
26.79


ATOM
2157
OD1
ASN
A
638
48.461
29.698
21.684
1.00
25.82


ATOM
2158
ND2
ASN
A
638
48.861
30.719
23.647
1.00
27.55


ATOM
2159
C
ASN
A
638
48.215
26.811
21.829
1.00
21.26


ATOM
2160
O
ASN
A
638
49.211
26.754
21.108
1.00
20.39


ATOM
2161
N
TRP
A
639
46.996
26.509
21.398
1.00
21.08


ATOM
2162
CA
TRP
A
639
46.752
26.050
20.031
1.00
21.27


ATOM
2163
CB
TRP
A
639
45.269
25.727
19.848
1.00
19.17


ATOM
2164
CG
TRP
A
639
44.831
24.646
20.779
1.00
19.03


ATOM
2165
CD2
TRP
A
639
44.866
23.236
20.530
1.00
17.97


ATOM
2166
CE2
TRP
A
639
44.434
22.594
21.709
1.00
17.66


ATOM
2167
CE3
TRP
A
639
45.223
22.452
19.423
1.00
16.87


ATOM
2168
CD1
TRP
A
639
44.391
24.797
22.058
1.00
18.23


ATOM
2169
NE1
TRP
A
639
44.150
23.572
22.626
1.00
18.28


ATOM
2170
CZ2
TRP
A
639
44.345
21.202
21.818
1.00
17.89


ATOM
2171
CZ3
TRP
A
639
45.135
21.065
19.528
1.00
15.97


ATOM
2172
CH2
TRP
A
639
44.698
20.454
20.720
1.00
18.31


ATOM
2173
C
TRP
A
639
47.228
26.958
18.916
1.00
21.59


ATOM
2174
O
TRP
A
639
47.739
26.483
17.898
1.00
22.22


ATOM
2175
N
GLU
A
640
47.074
28.261
19.090
1.00
21.76


ATOM
2176
CA
GLU
A
640
47.528
29.174
18.057
1.00
23.40


ATOM
2177
CB
GLU
A
640
47.065
30.584
18.362
1.00
26.20


ATOM
2178
CG
GLU
A
640
45.569
30.708
18.357
1.00
30.88


ATOM
2179
CD
GLU
A
640
45.135
32.134
18.488
1.00
32.97


ATOM
2180
OE1
GLU
A
640
45.463
32.935
17.586
1.00
35.29


ATOM
2181
OE2
GLU
A
640
44.476
32.447
19.497
1.00
36.31


ATOM
2182
C
GLU
A
640
49.037
29.147
17.933
1.00
22.82


ATOM
2183
O
GLU
A
640
49.571
29.147
16.828
1.00
22.84


ATOM
2184
N
GLU
A
641
49.729
29.136
19.065
1.00
22.39


ATOM
2185
CA
GLU
A
641
51.186
29.094
19.031
1.00
23.98


ATOM
2186
CB
GLU
A
641
51.776
29.251
20.434
1.00
26.01


ATOM
2187
CG
GLU
A
641
51.439
30.561
21.124
1.00
31.35


ATOM
2188
CD
GLU
A
641
52.274
30.783
22.372
1.00
34.23


ATOM
2189
OE1
GLU
A
641
52.348
29.872
23.225
1.00
36.36


ATOM
2190
OE2
GLU
A
641
52.858
31.875
22.502
1.00
38.31


ATOM
2191
C
GLU
A
641
51.640
27.756
18.454
1.00
23.36


ATOM
2192
O
GLU
A
641
52.658
27.680
17.761
1.00
22.24


ATOM
2193
N
LEU
A
642
50.879
26.703
18.744
1.00
22.32


ATOM
2194
CA
LEU
A
642
51.219
25.371
18.250
1.00
23.34


ATOM
2195
CB
LEU
A
642
50.221
24.323
18.764
1.00
21.57


ATOM
2196
CG
LEU
A
642
50.513
22.875
18.338
1.00
21.78


ATOM
2197
CD1
LEU
A
642
51.791
22.400
19.001
1.00
21.06


ATOM
2198
CD2
LEU
A
642
49.355
21.956
18.719
1.00
19.88


ATOM
2199
C
LEU
A
642
51.218
25.375
16.728
1.00
23.43


ATOM
2200
O
LEU
A
642
52.178
24.925
16.101
1.00
23.67


ATOM
2201
N
GLU
A
643
50.148
25.900
16.138
1.00
23.70


ATOM
2202
CA
GLU
A
643
50.043
25.948
14.688
1.00
24.81


ATOM
2203
CB
GLU
A
643
48.658
26.452
14.257
1.00
24.68


ATOM
2204
CG
GLU
A
643
48.483
26.454
12.745
1.00
26.60


ATOM
2205
CD
GLU
A
643
47.038
26.569
12.298
1.00
27.36


ATOM
2206
OE1
GLU
A
643
46.821
26.936
11.121
1.00
28.53


ATOM
2207
OE2
GLU
A
643
46.125
26.287
13.101
1.00
26.79


ATOM
2208
C
GLU
A
643
51.136
26.820
14.079
1.00
25.41


ATOM
2209
O
GLU
A
643
51.582
26.572
12.959
1.00
24.61


ATOM
2210
N
ARG
A
644
51.563
27.843
14.813
1.00
26.83


ATOM
2211
CA
ARG
A
644
52.626
28.719
14.331
1.00
28.50


ATOM
2212
CB
ARG
A
644
52.551
30.095
15.005
1.00
29.97


ATOM
2213
CG
ARG
A
644
51.364
30.947
14.557
1.00
31.25


ATOM
2214
CD
ARG
A
644
51.617
32.428
14.813
1.00
33.14


ATOM
2215
NE
ARG
A
644
51.705
32.749
16.234
1.00
34.76


ATOM
2216
CZ
ARG
A
644
50.656
32.828
17.044
1.00
36.97


ATOM
2217
NH1
ARG
A
644
49.437
32.613
16.568
1.00
37.67


ATOM
2218
NH2
ARG
A
644
50.825
33.120
18.329
1.00
37.98


ATOM
2219
C
ARG
A
644
53.969
28.071
14.626
1.00
29.00


ATOM
2220
O
ARG
A
644
55.023
28.635
14.339
1.00
28.66


ATOM
2221
N
LYS
A
645
53.916
26.875
15.203
1.00
30.31


ATOM
2222
CA
LYS
A
645
55.114
26.120
15.553
1.00
32.34


ATOM
2223
CB
LYS
A
645
55.872
25.715
14.283
1.00
32.10


ATOM
2224
CG
LYS
A
645
55.185
24.595
13.509
1.00
33.62


ATOM
2225
CD
LYS
A
645
55.978
24.184
12.282
1.00
35.74


ATOM
2226
CE
LYS
A
645
56.003
25.306
11.264
1.00
37.15


ATOM
2227
NZ
LYS
A
645
56.787
24.936
10.063
1.00
40.47


ATOM
2228
C
LYS
A
645
56.042
26.866
16.503
1.00
33.09


ATOM
2229
O
LYS
A
645
57.263
26.846
16.346
1.00
33.06


ATOM
2230
N
GLU
A
646
55.453
27.511
17.502
1.00
33.86


ATOM
2231
CA
GLU
A
646
56.225
28.254
18.483
1.00
35.00


ATOM
2232
CB
GLU
A
646
55.568
29.613
18.725
1.00
35.84


ATOM
2233
CG
GLU
A
646
55.268
30.319
17.412
1.00
37.58


ATOM
2234
CD
GLU
A
646
54.806
31.749
17.574
1.00
38.66


ATOM
2235
OE1
GLU
A
646
54.026
32.034
18.508
1.00
39.13


ATOM
2236
OE2
GLU
A
646
55.214
32.589
16.745
1.00
40.48


ATOM
2237
C
GLU
A
646
56.339
27.447
19.770
1.00
35.47


ATOM
2238
O
GLU
A
646
56.824
27.933
20.791
1.00
36.41


ATOM
2239
N
ILE
A
647
55.878
26.204
19.707
1.00
35.36


ATOM
2240
CA
ILE
A
647
55.955
25.290
20.834
1.00
35.47


ATOM
2241
CB
ILE
A
647
54.571
24.703
21.190
1.00
35.20


ATOM
2242
CG2
ILE
A
647
54.713
23.671
22.302
1.00
33.81


ATOM
2243
CG1
ILE
A
647
53.622
25.828
21.618
1.00
35.13


ATOM
2244
CD1
ILE
A
647
52.235
25.355
22.030
1.00
33.56


ATOM
2245
C
ILE
A
647
56.873
24.164
20.377
1.00
37.06


ATOM
2246
O
ILE
A
647
56.533
23.416
19.461
1.00
37.68


ATOM
2247
N
ASP
A
648
58.045
24.059
20.997
1.00
38.56


ATOM
2248
CA
ASP
A
648
59.013
23.025
20.639
1.00
40.29


ATOM
2249
CB
ASP
A
648
60.322
23.232
21.405
1.00
42.67


ATOM
2250
CG
ASP
A
648
61.016
24.528
21.040
1.00
45.84


ATOM
2251
OD1
ASP
A
648
60.430
25.607
21.275
1.00
47.54


ATOM
2252
OD2
ASP
A
648
62.153
24.467
20.521
1.00
48.45


ATOM
2253
C
ASP
A
648
58.486
21.622
20.930
1.00
40.04


ATOM
2254
O
ASP
A
648
57.721
21.419
21.872
1.00
38.73


ATOM
2255
N
PRO
A
649
58.891
20.635
20.113
1.00
40.99


ATOM
2256
CD
PRO
A
649
59.642
20.810
18.858
1.00
41.23


ATOM
2257
CA
PRO
A
649
58.474
19.237
20.271
1.00
41.88


ATOM
2258
CB
PRO
A
649
59.185
18.538
19.118
1.00
41.36


ATOM
2259
CG
PRO
A
649
59.227
19.596
18.065
1.00
40.72


ATOM
2260
C
PRO
A
649
58.887
18.668
21.627
1.00
43.01


ATOM
2261
O
PRO
A
649
58.087
18.025
22.310
1.00
45.59


ATOM
2262
N
GLN
A
688
41.314
7.240
−24.146
1.00
83.82


ATOM
2263
CA
GLN
A
688
42.769
7.135
−24.124
1.00
83.73


ATOM
2264
CB
GLN
A
688
43.215
7.098
−25.580
1.00
83.75


ATOM
2265
CG
GLN
A
688
44.097
8.259
−25.932
1.00
83.71


ATOM
2266
CD
GLN
A
688
45.193
7.784
−26.854
1.00
83.92


ATOM
2267
OE1
GLN
A
688
45.538
8.351
−27.892
1.00
83.95


ATOM
2268
NE2
GLN
A
688
45.763
6.636
−26.451
1.00
83.84


ATOM
2269
C
GLN
A
688
43.451
8.249
−23.348
1.00
83.82


ATOM
2270
O
GLN
A
688
44.406
8.040
−22.612
1.00
83.80


ATOM
2271
N
ASN
A
689
42.906
9.466
−23.474
1.00
83.51


ATOM
2272
CA
ASN
A
689
43.489
10.638
−22.833
1.00
83.17


ATOM
2273
CB
ASN
A
689
43.071
11.853
−23.685
1.00
83.43


ATOM
2274
CG
ASN
A
689
43.546
11.712
−25.110
1.00
83.69


ATOM
2275
OD1
ASN
A
689
44.764
11.714
−25.356
1.00
84.06


ATOM
2276
ND2
ASN
A
689
42.626
11.582
−26.042
1.00
83.71


ATOM
2277
C
ASN
A
689
43.248
10.870
−21.349
1.00
82.77


ATOM
2278
O
ASN
A
689
43.497
11.952
−20.833
1.00
82.58


ATOM
2279
N
MET
A
690
42.815
9.811
−20.670
1.00
82.42


ATOM
2280
CA
MET
A
690
42.543
9.813
−19.231
1.00
82.16


ATOM
2281
CB
MET
A
690
42.735
8.400
−18.667
1.00
82.70


ATOM
2282
CG
MET
A
690
41.516
7.537
−18.874
1.00
83.62


ATOM
2283
SD
MET
A
690
39.999
8.450
−18.468
1.00
84.51


ATOM
2284
CE
MET
A
690
39.003
7.203
−17.691
1.00
84.56


ATOM
2285
C
MET
A
690
43.228
10.790
−18.283
1.00
81.66


ATOM
2286
O
MET
A
690
42.568
11.362
−17.429
1.00
81.44


ATOM
2287
N
PHE
A
691
44.530
11.007
−18.415
1.00
81.19


ATOM
2288
CA
PHE
A
691
45.202
11.917
−17.479
1.00
80.70


ATOM
2289
CB
PHE
A
691
46.234
11.132
−16.670
1.00
80.81


ATOM
2290
CG
PHE
A
691
45.918
9.669
−16.538
1.00
80.86


ATOM
2291
CD1
PHE
A
691
46.505
8.737
−17.388
1.00
80.98


ATOM
2292
CD2
PHE
A
691
45.024
9.222
−15.568
1.00
81.28


ATOM
2293
CE1
PHE
A
691
46.211
7.385
−17.276
1.00
81.55


ATOM
2294
CE2
PHE
A
691
44.724
7.868
−15.448
1.00
81.78


ATOM
2295
CZ
PHE
A
691
45.319
6.949
−16.304
1.00
81.86


ATOM
2296
C
PHE
A
691
45.890
13.136
−18.086
1.00
80.23


ATOM
2297
O
PHE
A
691
47.095
13.334
−17.909
1.00
79.78


ATOM
2298
N
ARG
A
692
45.127
13.948
−18.804
1.00
80.06


ATOM
2299
CA
ARG
A
692
45.686
15.140
−19.434
1.00
80.00


ATOM
2300
CB
ARG
A
692
44.936
15.437
−20.728
1.00
80.57


ATOM
2301
CG
ARG
A
692
45.745
16.213
−21.722
1.00
81.51


ATOM
2302
CD
ARG
A
692
45.071
17.518
−22.074
1.00
82.17


ATOM
2303
NE
ARG
A
692
44.443
17.467
−23.388
1.00
82.75


ATOM
2304
CZ
ARG
A
692
44.169
18.547
−24.109
1.00
82.92


ATOM
2305
NH1
ARG
A
692
44.470
19.745
−23.630
1.00
82.73


ATOM
2306
NH2
ARG
A
692
43.608
18.433
−25.306
1.00
83.03


ATOM
2307
C
ARG
A
692
45.623
16.347
−18.495
1.00
79.58


ATOM
2308
O
ARG
A
692
44.663
16.508
−17.744
1.00
79.25


ATOM
2309
N
ASN
A
693
46.653
17.191
−18.544
1.00
79.24


ATOM
2310
CA
ASN
A
693
46.735
18.379
−17.691
1.00
78.70


ATOM
2311
CB
ASN
A
693
45.475
19.234
−17.831
1.00
78.66


ATOM
2312
CG
ASN
A
693
45.669
20.401
−18.771
1.00
78.73


ATOM
2313
OD1
ASN
A
693
44.724
21.123
−19.084
1.00
79.24


ATOM
2314
ND2
ASN
A
693
46.902
20.600
−19.220
1.00
78.29


ATOM
2315
C
ASN
A
693
46.929
17.985
−16.238
1.00
78.26


ATOM
2316
O
ASN
A
693
46.594
18.736
−15.315
1.00
77.68


ATOM
2317
N
PHE
A
694
47.481
16.794
−16.042
1.00
78.23


ATOM
2318
CA
PHE
A
694
47.731
16.269
−14.707
1.00
78.24


ATOM
2319
CB
PHE
A
694
47.923
14.757
−14.773
1.00
78.00


ATOM
2320
CG
PHE
A
694
48.428
14.166
−13.491
1.00
78.00


ATOM
2321
CD1
PHE
A
694
47.583
14.024
−12.393
1.00
77.64


ATOM
2322
CD2
PHE
A
694
49.760
13.789
−13.364
1.00
77.71


ATOM
2323
CE1
PHE
A
694
48.061
13.509
−11.188
1.00
77.25


ATOM
2324
CE2
PHE
A
694
50.248
13.273
−12.165
1.00
77.28


ATOM
2325
CZ
PHE
A
694
49.396
13.132
−11.075
1.00
77.21


ATOM
2326
C
PHE
A
694
48.963
16.902
−14.080
1.00
78.53


ATOM
2327
O
PHE
A
694
49.072
16.982
−12.857
1.00
78.24


ATOM
2328
N
SER
A
695
49.877
17.345
−14.941
1.00
79.31


ATOM
2329
CA
SER
A
695
51.127
17.966
−14.492
1.00
80.01


ATOM
2330
C
SER
A
695
50.844
19.279
−13.788
1.00
79.90


ATOM
2331
O
SER
A
695
49.834
19.926
−14.055
1.00
79.91


ATOM
2332
OG
SER
A
695
51.914
17.184
−16.614
1.00
82.44


ATOM
2333
CB
SER
A
695
52.033
18.234
−15.681
1.00
80.87


ATOM
2334
N
PHE
A
696
51.769
19.663
−12.917
1.00
79.79


ATOM
2335
CA
PHE
A
696
51.592
20.863
−12.165
1.00
79.91


ATOM
2336
CB
PHE
A
696
50.313
20.684
−11.292
1.00
79.86


ATOM
2337
CG
PHE
A
696
50.348
21.362
−9.959
1.00
79.95


ATOM
2338
CD1
PHE
A
696
51.375
21.095
−9.055
1.00
80.04


ATOM
2339
CD2
PHE
A
696
49.290
22.184
−9.579
1.00
80.04


ATOM
2340
CE1
PHE
A
696
51.367
21.633
−7.797
1.00
80.18


ATOM
2341
CE2
PHE
A
696
49.274
22.737
−8.293
1.00
80.17


ATOM
2342
CZ
PHE
A
696
50.317
22.454
−7.405
1.00
80.32


ATOM
2343
C
PHE
A
696
52.806
21.120
−11.337
1.00
79.99


ATOM
2344
O
PHE
A
696
53.315
20.153
−10.786
1.00
80.34


ATOM
2345
OXT
PHE
A
696
53.291
22.241
−11.239
1.00
80.10


ATOM
2346
O
HOH
W
1
44.405
−5.257
16.067
1.00
27.81


ATOM
2347
O
HOH
W
2
43.908
−7.626
15.396
1.00
31.97


ATOM
2348
O
HOH
W
3
38.566
0.748
15.081
1.00
17.03


ATOM
2349
O
HOH
W
4
51.061
33.563
21.928
1.00
46.43


ATOM
2350
O
HOH
W
5
37.775
5.803
−2.008
1.00
43.14


ATOM
2351
O
HOH
W
6
40.381
8.066
9.339
1.00
10.44


ATOM
2352
O
HOH
W
7
61.824
18.216
0.279
1.00
20.16


ATOM
2353
O
HOH
W
8
43.782
24.225
12.173
1.00
18.02


ATOM
2354
O
HOH
W
9
31.125
0.199
0.285
1.00
19.97


ATOM
2355
O
HOH
W
10
42.051
−3.360
24.518
1.00
21.43


ATOM
2356
O
HOH
W
11
55.788
23.461
6.982
1.00
27.61


ATOM
2357
O
HOH
W
12
52.691
6.016
27.604
1.00
16.16


ATOM
2358
O
HOH
W
13
29.699
−1.807
1.877
1.00
23.21


ATOM
2359
O
HOH
W
14
42.543
21.972
26.847
1.00
20.54


ATOM
2360
O
HOH
W
15
54.858
19.831
10.485
1.00
28.97


ATOM
2361
O
HOH
W
16
27.082
7.849
11.073
1.00
20.41


ATOM
2362
O
HOH
W
17
59.280
15.191
17.943
1.00
16.31


ATOM
2363
O
HOH
W
18
36.410
18.910
15.687
1.00
22.10


ATOM
2364
O
HOH
W
19
35.848
19.335
18.774
1.00
30.89


ATOM
2365
O
HOH
W
20
50.064
12.660
0.176
1.00
32.24


ATOM
2366
O
HOH
W
21
28.589
10.090
11.006
1.00
17.76


ATOM
2367
O
HOH
W
22
60.540
19.603
−7.946
1.00
51.97


ATOM
2368
O
HOH
W
23
35.553
17.240
27.309
1.00
33.05


ATOM
2369
O
HOH
W
24
27.328
15.237
13.103
1.00
43.62


ATOM
2370
O
HOH
W
25
36.165
23.947
17.186
1.00
50.30


ATOM
2371
O
HOH
W
26
35.357
20.052
−0.144
1.00
15.44


ATOM
2372
O
HOH
W
27
36.806
22.336
11.783
1.00
43.54


ATOM
2373
O
HOH
W
28
38.060
4.589
0.128
1.00
49.83


ATOM
2374
O
HOH
W
29
43.220
−9.174
10.881
1.00
44.22


ATOM
2375
O
HOH
W
30
41.490
25.041
11.497
1.00
35.34


ATOM
2376
O
HOH
W
31
67.616
18.210
0.377
1.00
30.10


ATOM
2377
O
HOH
W
32
24.046
14.749
11.303
1.00
45.32


ATOM
2378
O
HOH
W
33
36.391
18.472
13.067
1.00
26.28


ATOM
2379
O
HOH
W
34
54.306
24.084
17.765
1.00
29.86


ATOM
2380
O
HOH
W
35
44.689
24.321
25.503
1.00
28.37


ATOM
2381
O
HOH
W
36
42.290
−1.232
16.750
1.00
16.71


ATOM
2382
O
HOH
W
37
36.342
3.064
26.596
1.00
33.46


ATOM
2383
O
HOH
W
38
48.333
19.882
28.225
1.00
30.75


ATOM
2384
O
HOH
W
39
57.496
7.469
30.873
1.00
34.58


ATOM
2385
O
HOH
W
40
50.553
5.293
3.188
1.00
36.61


ATOM
2386
O
HOH
W
41
70.620
20.787
−1.977
1.00
54.10


ATOM
2387
O
HOH
W
42
47.632
−2.376
34.252
1.00
32.36


ATOM
2388
O
HOH
W
43
37.180
5.176
10.395
1.00
28.30


ATOM
2389
O
HOH
W
44
65.382
14.396
11.655
1.00
31.23


ATOM
2390
O
HOH
W
45
57.263
1.539
4.750
1.00
49.90


ATOM
2391
O
HOH
W
46
44.607
28.285
22.864
1.00
26.64


ATOM
2392
O
HOH
W
47
34.058
4.713
25.333
1.00
42.08


ATOM
2393
O
HOH
W
48
49.651
16.194
28.767
1.00
37.23


ATOM
2394
O
HOH
W
49
50.072
7.974
31.762
1.00
23.99


ATOM
2395
O
HOH
W
50
49.465
19.105
33.214
1.00
53.04


ATOM
2396
O
HOH
W
51
24.188
7.651
14.892
1.00
43.42


ATOM
2397
O
HOH
W
52
65.318
2.953
−5.733
1.00
53.32


ATOM
2398
O
HOH
W
53
34.951
9.039
−3.115
1.00
31.77


ATOM
2399
O
HOH
W
54
62.788
16.520
6.541
1.00
27.93


ATOM
2400
O
HOH
W
55
65.317
0.908
−1.037
1.00
39.92


ATOM
2401
O
HOH
W
56
22.736
6.224
7.854
1.00
37.18


ATOM
2402
O
HOH
W
57
22.354
−0.345
8.024
1.00
45.57


ATOM
2403
O
HOH
W
58
39.754
−10.441
4.356
1.00
41.90


ATOM
2404
O
HOH
W
59
28.903
2.816
5.921
1.00
36.89


ATOM
2405
O
HOH
W
60
51.831
3.389
5.105
1.00
41.56


ATOM
2406
O
HOH
W
61
68.191
17.402
−12.335
1.00
28.50


ATOM
2407
O
HOH
W
62
38.575
−5.049
5.076
1.00
32.80


ATOM
2408
O
HOH
W
63
67.628
6.871
−10.290
1.00
32.96


ATOM
2409
O
HOH
W
64
61.069
15.027
−16.486
1.00
44.39


ATOM
2410
O
HOH
W
65
51.197
21.314
−1.255
1.00
33.50


ATOM
2411
O
HOH
W
66
43.407
−8.262
13.149
1.00
43.24


ATOM
2412
O
HOH
W
67
28.328
20.172
21.424
1.00
55.05


ATOM
2413
O
HOH
W
68
24.787
13.752
1.867
1.00
33.58


ATOM
2414
O
HOH
W
69
56.831
16.690
24.349
1.00
42.38


ATOM
2415
O
HOH
W
70
49.409
8.548
−21.438
1.00
44.91


ATOM
2416
O
HOH
W
71
52.613
18.410
25.629
1.00
40.22


ATOM
2417
O
HOH
W
72
40.592
26.447
8.059
1.00
35.07


ATOM
2418
O
HOH
W
73
37.597
5.018
7.744
1.00
32.52


ATOM
2419
O
HOH
W
74
41.658
29.146
4.538
1.00
34.36


ATOM
2420
O
HOH
W
75
29.114
3.872
23.333
1.00
37.14


ATOM
2421
O
HOH
W
76
47.138
27.828
26.613
1.00
45.54


ATOM
2422
O
HOH
W
77
48.429
14.683
34.149
1.00
45.72


ATOM
2423
O
HOH
W
78
44.818
26.959
9.627
1.00
36.07


ATOM
2424
O
HOH
W
79
32.245
16.035
7.600
1.00
29.86


ATOM
2425
O
HOH
W
80
34.287
18.006
20.219
1.00
49.58


ATOM
2426
O
HOH
W
81
46.140
8.973
36.904
1.00
41.01


ATOM
2427
O
HOH
W
82
36.178
13.580
−3.440
1.00
35.51


ATOM
2428
O
HOH
W
83
43.909
13.668
37.111
1.00
58.57


ATOM
2429
O
HOH
W
84
28.754
0.872
3.464
1.00
53.40


ATOM
2430
O
HOH
W
85
58.227
−2.893
27.346
1.00
35.17


ATOM
2431
O
HOH
W
86
51.679
−1.044
27.253
1.00
32.70


ATOM
2432
O
HOH
W
87
54.344
−1.547
20.337
1.00
40.72


ATOM
2433
O
HOH
W
88
55.722
20.496
−13.650
1.00
57.49


ATOM
2434
O
HOH
W
89
28.429
13.038
−1.037
1.00
46.69


ATOM
2435
O
HOH
W
90
29.231
9.216
−1.912
1.00
46.23


ATOM
2436
O
HOH
W
91
54.865
1.093
3.517
1.00
43.59


ATOM
2437
O
HOH
W
92
58.721
1.874
6.787
1.00
50.25


ATOM
2438
O
HOH
W
93
64.156
3.084
3.700
1.00
51.88


ATOM
2439
O
HOH
W
94
65.008
6.626
5.313
1.00
46.57


ATOM
2440
O
HOH
W
95
64.832
4.948
10.246
1.00
61.80


ATOM
2441
O
HOH
W
96
74.347
21.947
−3.124
1.00
52.18


ATOM
2442
O
HOH
W
97
76.689
18.777
−2.619
1.00
61.15


ATOM
2443
O
HOH
W
98
38.819
−15.466
14.853
1.00
41.26


ATOM
2444
O
HOH
W
99
37.941
10.962
−12.972
1.00
48.80


ATOM
2445
O
HOH
W
100
32.483
6.619
−4.835
1.00
39.40


ATOM
2446
O
HOH
W
101
48.304
28.153
9.505
1.00
34.82


ATOM
2447
O
HOH
W
102
51.901
−2.777
16.129
1.00
48.45


ATOM
2448
O
HOH
W
103
45.328
12.905
34.608
1.00
38.67


ATOM
2449
O
HOH
W
104
32.098
11.673
24.028
1.00
31.67


ATOM
2450
O
HOH
W
105
48.096
7.776
37.247
1.00
61.92


ATOM
2451
O
HOH
W
106
60.343
17.220
−15.584
1.00
47.08


ATOM
2452
O
HOH
W
107
41.259
28.308
6.780
1.00
48.27


ATOM
2453
O
HOH
W
108
51.326
8.898
36.188
1.00
41.59


ATOM
2454
O
HOH
W
109
30.252
22.907
5.497
1.00
52.21


ATOM
2455
O
HOH
W
110
57.413
20.830
9.293
1.00
46.14


ATOM
2456
O
HOH
W
111
46.088
14.217
41.579
1.00
42.28


ATOM
2457
O
HOH
W
112
40.128
1.136
2.224
1.00
32.09


ATOM
2458
O
HOH
W
113
33.992
17.400
6.607
1.00
41.25


ATOM
2459
O
HOH
W
114
54.842
22.676
31.236
1.00
62.02


ATOM
2460
O
HOH
W
115
48.235
−0.372
10.526
1.00
51.22


ATOM
2461
O5
STU
A
1
59.277
12.216
3.424
1.00
21.44


ATOM
2462
C8
STU
A
1
58.213
11.942
2.911
1.00
19.74


ATOM
2463
N1
STU
A
1
57.427
12.742
2.229
1.00
18.27


ATOM
2464
C7
STU
A
1
57.488
10.647
2.887
1.00
19.44


ATOM
2465
C6
STU
A
1
57.931
9.292
3.545
1.00
19.72


ATOM
2466
C5
STU
A
1
58.992
8.833
4.330
1.00
21.14


ATOM
2467
C20
STU
A
1
58.755
7.365
4.590
1.00
22.15


ATOM
2468
C1
STU
A
1
59.705
6.568
5.431
1.00
22.07


ATOM
2469
C2
STU
A
1
60.918
7.223
5.917
1.00
22.36


ATOM
2470
C3
STU
A
1
61.177
8.665
5.634
1.00
21.99


ATOM
2471
C4
STU
A
1
60.241
9.426
4.840
1.00
21.85


ATOM
2472
N3
STU
A
1
57.542
6.993
4.044
1.00
21.06


ATOM
2473
C19
STU
A
1
56.975
8.152
3.343
1.00
20.78


ATOM
2474
C25
STU
A
1
57.043
5.523
3.938
1.00
21.48


ATOM
2475
O4
STU
A
1
56.126
5.390
2.811
1.00
21.40


ATOM
2476
C10
STU
A
1
56.331
10.786
2.200
1.00
19.21


ATOM
2477
C9
STU
A
1
56.206
12.205
1.700
1.00
18.62


ATOM
2478
C11
STU
A
1
55.387
9.642
1.986
1.00
19.47


ATOM
2479
C12
STU
A
1
54.129
9.482
1.354
1.00
19.14


ATOM
2480
C13
STU
A
1
53.280
10.398
0.573
1.00
17.85


ATOM
2481
C14
STU
A
1
52.012
9.993
−0.013
1.00
17.84


ATOM
2482
C15
STU
A
1
51.571
8.563
0.145
1.00
18.71


ATOM
2483
C17
STU
A
1
53.682
8.044
1.472
1.00
19.90


ATOM
2484
C16
STU
A
1
52.377
7.645
0.890
1.00
20.47


ATOM
2485
C18
STU
A
1
55.759
8.309
2.603
1.00
19.80


ATOM
2486
N2
STU
A
1
54.678
7.380
2.283
1.00
20.08


ATOM
2487
C21
STU
A
1
54.759
5.875
2.756
1.00
20.72


ATOM
2488
C26
STU
A
1
54.119
4.791
1.859
1.00
21.87


ATOM
2489
C22
STU
A
1
53.967
5.789
4.219
1.00
21.57


ATOM
2490
O6
STU
A
1
54.005
7.111
4.939
1.00
22.98


ATOM
2491
C27
STU
A
1
52.783
7.836
4.894
1.00
21.48


ATOM
2492
C23
STU
A
1
54.712
4.695
5.051
1.00
22.41


ATOM
2493
C24
STU
A
1
56.254
5.136
5.300
1.00
22.58


ATOM
2494
N4
STU
A
1
54.087
4.411
6.485
1.00
25.14


ATOM
2495
C28
STU
A
1
54.826
3.300
7.233
1.00
24.32


ATOM
2496
O1P
TPB
A
2
34.001
6.990
−1.433
1.00
18.24


ATOM
2497
O2P
TPB
A
2
32.139
7.348
0.244
1.00
20.04


ATOM
2498
O3P
TPB
A
2
31.766
7.269
−2.303
1.00
18.89


ATOM
2499
P
TPB
A
2
32.585
6.763
−1.066
1.00
21.60


ATOM
2500
O1P
SPB
A
3
53.748
18.218
−17.683
1.00
83.37


ATOM
2501
O2P
SPB
A
3
51.814
16.872
−18.638
1.00
83.11


ATOM
2502
O3P
SPB
A
3
53.921
15.822
−17.583
1.00
83.40


ATOM
2503
P
SPB
A
3
52.898
17.012
−17.594
1.00
83.90









Other embodiments are within the scope of the claims.

## Claims

1. A method of designing a candidate agent that interacts with protein kinase C theta (PKCθ), comprising:
(a) generating a three-dimensional model of the catalytic domain of PKCθ defined by the three-dimensional structural coordinates of the complex of the catalytic domain of PKCθ and staurosporine according to Table 2, ± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å, wherein the catalytic domain of PKCθ of the complex according to Table 2 consists of amino acids Ile377 to Pro649 and Gln688 to Phe696 of SEQ ID NO: 1;
(b) identifying the amino acid residues forming the ATP-binding pocket of the catalytic domain of PKCθ from the three-dimensional model in step (a) in order to generate a three-dimensional representation of the ATP-binding pocket which comprises the structural coordinates of residues Leu386, Gly387, Gly389, Val394, Ala407, Lys409, Val422, Glu428, Met458, Glu459, Tyr460, Leu461, Gly464, Leu466, Arg503, Asp504, Asp508, Asn509, Leu511, Ala521, Asp522, Lys527, Thr536, and Thr538 according to Table 2± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å;
(c) employing said three-dimensional representation from step (b) to design said candidate agent;
(d) synthesizing said candidate agent;
(e) contacting said candidate agent with said catalytic domain of PKCθ polypeptide; and
(f) detecting the ability of the candidate agent to bind to the catalytic domain of the PKCθ polypeptide,
whereby the detection of the ability of said candidate agent to interact or bind said catalytic domain of PKCθ polypeptide thereby identifies said candidate agent as an agent that interacts with PKCθ.

2. The method of claim 1, wherein the complex of the catalytic domain of PKCθ and staurosporine is a crystalline complex and has a space group symmetry C2, with dimensions a=139.6 Å, b=42.4 Å, c=67.7 Å and β=116.2°.

3. The method of claim 1, wherein the contacting of said candidate agent with said catalytic domain of PKCθ polypeptide occurs in vitro or in a cell-based assay.

4. The method of claim 1, wherein the three-dimensional model comprises structural coordinates of atoms of the candidate agent.

5. The method of claim 4, further comprising altering the structural coordinates of the candidate agent of the model.

6. The method of claim 1, wherein the three-dimensional representation further comprises structural coordinates of residues Lys413, Va1416, Leu417, Met426, Lys429, Thr447, Gln449, Leu454, Phe456, Phe691, Arg692, Asn693, Phe694, and Ser695 according to Table 2± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å.

7. The method of claim 1, wherein designing of the candidate agent comprises calculating a distance between an atom of the PKCθ and an atom of the candidate agent.

8. The method of claim 4, further comprising calculating a distance between atoms of the PKCθ and atoms of the candidate agent.

9. The method of claim 1, wherein designing of the candidate agent comprises docking a three-dimensional model of the candidate agent to the three-dimensional model of the catalytic domain of PKCθ.

10. The method of claim 1, wherein the PKCθ polypeptide used in steps (e) and (f) comprises a catalytic domain from amino acids 362 to 706 of SEQ ID NO: 1.

11. The method of claim 1, further comprising determining a catalytic activity of the PKCθ polypeptide.

12. The method of claim 1, further comprising comparing the catalytic activity of a PKCθ polypeptide determined in the presence of the candidate agent to a catalytic activity of the PKCθ polypeptide determined in the absence of the candidate agent.

13. The method of claim 12, wherein the catalytic activity of PKCθ is evaluated in vitro.

14. The method of claim 12, wherein the catalytic activity of PKCθ is evaluated in a cell-based assay.

15. A method of identifying a candidate agent capable of altering a catalytic activity of PKCθ comprising:
(a) generating a three-dimensional model of the catalytic domain of PKCθ defined by the three-dimensional structural coordinates of the complex of the catalytic domain of PKCθ and staurosporine according to Table 2, ± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å, wherein the catalytic domain of PKCθ in the complex according to Table 2 consists of amino acids Ile377 to Pro649 and Gln688 to Phe696 of SEQ ID NO: 1;
(b) identifying the amino acid residues forming the ATP-binding pocket of the catalytic domain of PKCθ from the three-dimensional model in step (a) in order to generate a three-dimensional representation of the ATP-binding pocket which comprises the structural coordinates of residues Leu386, Gly387, Gly389, Val394, Ala407, Lys409, Val422, Met458, Glu459, Tyr460, Leu461, Gly464, Leu466, Arg503, Asp504, Asp508, Asn509, Leu511, Ala521, Asp522, Lys527, Thr536, and Thr538 according to Table 2± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å;
(c) studying the interaction of a plurality of candidate agents with the three-dimensional representation of the ATP-binding pocket from step (b);
(d) selecting from the plurality of candidate agents an agent which is predicted to alter a catalytic activity of the catalytic domain of PKCθ; and
(e) determining a catalytic activity of the catalytic domain of a PKCθ polypeptide in the presence or the absence of the candidate agent.

16. The method of claim 15, wherein the catalytic domain of the PKCθ polypeptide according to step (e) comprises a catalytic domain from amino acids 362 to 706 of SEQ ID NO: 1.

17. A method of designing an agent that binds to a PKCθ polypeptide, comprising:
(a) generating a three-dimensional model of the catalytic domain of PKCθ defined by the three-dimensional structural coordinates of the crystalline complex of the catalytic domain of PKCθ and staurosporine according to Table 2, ± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å, wherein the catalytic domain of PKCθ in the complex according to Table 2 consists of amino acids Ile377 to Pro649 and Gln688 to Phe696 of SEQ ID NO: 1;
(b) identifying the amino acid residues forming the ATP-binding pocket of the catalytic domain of PKCθ from the three-dimensional model in step (a) in order to generate a three-dimensional representation of the ATP-binding pocket which comprises the structural coordinates of residues Leu386, Gly387, Gly389, Val394, Ala407, Lys409, Lys413, Val416, Leu417, Val422, Met426, Glu428, Lys429, Thr447, Gln449, Leu454, Phe456, Met458, Glu459, Tyr460, Leu461, Gly464, Leu466, Arg503, Asp504, Asp508, Asn509, Leu511, Ala521, Asp522, Lys527, Thr536, Thr538, Phe691, Arg692, Asn693, Phe694, and Ser695 according to Table 2± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å;
(c) selecting a candidate agent by performing rational drug design with the three-dimensional representation of the ATP-binding pocket from step (b);
(d) altering the structure of the candidate agent in the three-dimensional representation from step (b);
(e) contacting the candidate agent with the catalytic domain of a PKCθ polypeptide; and
(f) detecting the ability of the candidate agent to bind to the catalytic domain of the PKCθ polypeptide.

18. The method of claim 17, wherein the catalytic domain of the PKCθ polypeptide according to step (e) or (f) comprises a catalytic domain from amino acids 362 to 706 of SEQ ID NO: 1.

19. The method of claim 17, further comprising determining a catalytic activity of the PKCθ polypeptide.

20. The method of claim 17, wherein the crystalline complex has a space group symmetry C2, with dimensions a=139.6 Å, b=42.4 Å, c=67.7 Å and β=116.2°.

21. A method of designing a candidate agent that interacts with protein kinase C theta (PKCθ), comprising:
generating a three-dimensional model of a crystalline complex comprising the structural coordinates of a crystalline complex of a catalytic domain of a PKCθ and staurosporine defined by Table 2, ± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å, wherein the PKCθ in the complex according to Table 2 consists of the amino acid sequence of SEQ ID NO: 2, said structural coordinates of the crystalline complex being obtained by subjecting a co-crystal comprising the catalytic domain of PKCθ and staurosporine to X-ray diffraction and collecting data sufficient to determine the three-dimensional structure of said crystalline complex, wherein the crystalline complex has a space group symmetry C2, with dimensions a=139.6 Å, b=42.4 Å, c=67.7 Å and β=116.2°;
determining a fit between the structural coordinates of atoms of the three-dimensional model of the catalytic domain of PKCθ and a candidate;
altering the structure of the candidate agent in the three-dimensional model,
obtaining the candidate agent; and
detecting the ability of the candidate agent to bind to the catalytic domain of a PKCθ polypeptide.

22. The method of claim 21, wherein the PKCθ polypeptide of step (e) comprises a catalytic domain from amino acids 362 to 706 of SEQ ID NO: 1.

23. A method of designing a candidate agent that interacts with protein kinase C theta (PKCθ), comprising:
(a) generating a three-dimensional model of the catalytic domain of PKCθ defined by the three-dimensional structural coordinates of the crystalline complex of the catalytic domain of PKCθ and staurosporine according to Table 2± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å, wherein the catalytic domain of PKCθ in the complex according to Table 2 consists of amino acids lle377 to Pro649 and Gln688 to Phe696 of SEQ ID NO: 1;
(b) identifying the amino acid residues forming the ATP-binding pocket of the catalytic domain of PKCθ from the three-dimensional model in step (a) in order to generate a three-dimensional representation of the ATP-binding pocket which comprises the structural coordinates of residues Leu386, Gly387, Gly389, Val394, Ala407, Lys409, Lys413, Val416, Leu417, Va1422, Met426, Glu428, Lys429, Thr447, Gln449, Leu454, Phe456, Met458, Glu459, Tyr460, Leu461, Gly464, Leu466, Arg503, Asp504, Asp508, Asn509, Leu511, Ala521, Asp522, Lys527, Thr536, Thr538, Phe691, Arg692, Asn693, Phe694, and Ser695 according to Table 2± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å, wherein the ATP-binding pocket of the catalytic domain of PKCθ has a closed conformation;
(c) determining a fit between said three-dimensional model and a candidate agent;
(d) altering the structure of the candidate agent in the three-dimensional model,
(e) synthesizing the candidate agent; and
(f) detecting the ability of the candidate agent to bind to the catalytic domain of a PKCθ polypeptide.

24. The method of claim 23, wherein the PKCθ polypeptide of steps (e) and (f) comprises a catalytic domain from amino acids 362 to 706 of SEQ ID NO: 1.

25. A method of designing a candidate agent that interacts with protein kinase C theta (PKCθ), comprising:
(a) generating a three-dimensional model of the catalytic domain of PKCθ defined by the three-dimensional structural coordinates of the complex of the catalytic domain of PKCθ and staurosporine according to Table 2, ± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å, wherein the catalytic domain of PKCθ of the complex according to Table 2 consists of amino acids Ile377 to Pro649 and Gln688 to Phe696 of SEQ ID NO: 1;
(b) identifying the amino acid residues forming the ATP-binding pocket of the catalytic domain of PKCθ from the three-dimensional model in step (a) in order to generate a three-dimensional representation of the ATP-binding pocket which comprises the structural coordinates of residues Leu386, Gly387, Gly389, Val394, Ala407, Lys409, Val422, Glu428, Met458, Glu459, Tyr460, Leu461, Gly464, Leu466, Arg503, Asp504, Asp508, Asn509, Leu511, Ala521, Asp522, Lys527, Thr536, and Thr538 according to Table 2± a root mean square deviation for alpha carbon atoms of not more than 0.5 Å;
(c) employing said three-dimensional representation from step (b) to design said candidate agent;
(d) obtaining said candidate agent; and
(e) contacting said candidate agent with said catalytic domain of PKCθ to determine the ability of said candidate agent to interact or bind with said three-dimensional model of the catalytic domain of PKCθ,
whereby the detection of the ability of said candidate agent to interact or bind said catalytic domain of PKCθ thereby identifies said candidate agent as an agent that interacts with PKCθ.