# Patent

## Title
S8 rRNA-binding protein from the small ribosomal subunit of Staphylococcus aureus

## Abstract

A Staphylococcus aureus S8 native crystalline structure and a Staphylococcus aureus S8 mode of binding with rRNA were identified.

## Background
This application is a National Stage Application filed under 35 U.S.C. §371 of PCT/US02/32859, filed on 15 Oct. 2002 which claims the benefit of U.S. Provisional Application No. 60/329,439, filed 15 Oct. 2001.


TECHNICAL FIELD OF THE INVENTION
The invention relates to the identification of an RNA-binding domain, its mode of binding with a cognate RNA, and methods enabling design and selection of inhibitors of its binding site.
BACKGROUND OF THE INVENTION
With over 36 classes of known anti-ribosomal agents, the bacterial ribosome has been exploited for decades as a target for antibiotic drugs. The essentiality, selectivity, and conserved nature of bacterial translation continue to make the ribosome one of the most attractive targets for the discovery of antibacterial agents. The recent elucidation of the crystal structures of the 30S and 50S ribosomal subunits from Thermus thermophilus (Wimberly et al., (2000) Nature 407, 327-339) and Haloarcula matsumorii (Ban et al., (2000) Science 289, 905-920), respectively have provided an enormous amount of detailed structural information regarding RNA and protein structure, RNA-protein interactions, and ribosome assembly. In addition, these revolutionary discoveries have provided a structural basis for understanding the mechanistic processes of translation and the action of antibiotics, and may also allow for the de novo design of new antibacterial drugs that target the translation machinery.
Ribosomal protein S8 is an excellent target for the discovery of new antibacterials. In addition to being absolutely required for the proper assembly of the 30S ribosomal subunit in E. coli, the invention provide that S8 in S. pneumoniae is essential for bacterial growth. Moreover, alterations in S8-rRNA affinity can be correlated with growth defects that result from the expression of the same mutations in E. coli (Gregory and Zimmermann, (1986), Nucleic Acids Research 14, 5761-76). Ribosomal protein S8 is also a broad-spectrum target, as it is predicted to be very well conserved among bacterial species, see Table 1. Although there is a human ribosomal protein S8, it is significantly divergent and not thought to be a functional homolog of the bacterial S8. In addition, there does not appear to be any helix 21 homology in eukaryotic 18S rRNA.
Ribosomal protein S8 is a primary rRNA-binding protein that binds directly to a central region of bacterial 16S rRNA called Helix 21. Since S8 is required for the co-operative binding of all 30S proteins, it is essential for the proper assembly of the small ribosomal subunit (Held et al., (1974) J. Biol. Chem 249, 3101-3111). Indeed, mutations within the protein have been shown to result in ribosome assembly in defects in E. coli (Geyl et al. (1977) Mol Gen Genet. 29, 331-6). The binding site of S8 within Helix 21 rRNA has been extensively characterised in E. coli, and consists of two helical segments interrupted by a very highly conserved core element of irregular structure that spans nucleotides 595-598 and 640-644 of 16S rRNA. An unusual feature of this core element, which has been elucidated by NMR studies (Kalurachchi et al., (1 997) Proc. Natl Acad. Sci USA 94, 2139-2144), is the existence of a base triple element between nucleotides A595 and the A596/U644 base pair in the E. coli rRNA. The deletion of A595 severely impairs the binding of E. coli S8 (Mougel et al., (1993) Eur J. Biochem. 215, 787-792), indicating that this nucleotide is critical for RNA-protein recognition. Interestingly, this base triple is predicted by comparative phylogenetic evidence to be nearly universally-conserved in prokaryotes (Gutell (1993), Nucleic Acids Res. 21, 3051-3054).
While the S8-RNA interactions have been extensively characterized in E. coli, and the crystal structures of both B. stearothermophilus and T. Thermophilus S8 have been solved, prior to this invention very little was known regarding the structure and RNA-binding activities of ribosomal proteins from a pathogenic bacterial species. This problem is solved by the instant invention that provides cloned, expressed, and purified Staphylococcus aureus ribosomal protein S8, and RNA-binding studies showing a specific interaction between S8 and S. aureus or E. coli helix 21 RNAs. Mutagenesis studies also provided herein have defined nucleotides in the core RNA element from S. aureus that are essential for recognition by S8 and suggest a conservation of the structure of helix 21 in this organism. Also provided herein is a crystal structure of the native S8 protein from S. aureus to 1.56 Å resolution, and superimposition of this structure into the 30S ribosomal subunit structure of T. thermophilus has provided regions of contact with a cognate rRNA. Characterisation of S. aureus S8, taken together with a recent published crystal structure of the 30S ribosomal subunit (Wimberly et al., (2000) Nature 407, 327-339) advances understanding of bacterial ribosome architecture and allows for rational design of broad-spectrum antibiotics that target the translational apparatus.
The instant invention further provides a crystal structure of the protein S8 from the small ribosomal subunit of Staphylococcus aureus in its native state. A preferred structure shows that S8 presents two surfaces that are suited to bind a cognate rRNA. On of them is a α-helix that binds into the major groove of the double stranded rRNA. A second surface is one in which conserved residues are located and are critical for binding to a cognate rRNA. S8 interacts with rRNA through this second surface by an interaction that can be described as “riding” over the double helix. Given the significant role of S8 in organising and binding rRNA for proper ribosomal function and therefore proper protein synthesis, targeting either interaction between S8 and rRNA for disruption with small molecules could result in an effective antimicrobial.
SUMMARY OF THE INVENTION
In one aspect, the present invention relates to an S8 protein that is derived from Staphylococcus aureus and comprising a protein having the amino acid sequence shown in SEQ ID No. 1, and coordinates of Table 2 in an essentially pure native form or a homolog thereof.
In another aspect, the present invention provides a crystalline form of the S. aureus S8 rRNA-binding site as derived from models of S8 docked onto rRNA comprising coordinates of Table 2.
In yet another aspect, the invention provides structural coordinates of residues in a binding site responsible for binding of a rRNA.
In yet another aspect, the invention provides structural coordinates of a rRNA-binding-amino acid residues responsible for a function of S8 or involved in binding S8. The invention further provides a method for identifying inhibitors of an S8-rRNA interaction, which method comprises the steps of: providing coordinates of an S8 structure of the invention to a computerized modeling system; identifying compounds that will bind to the binding site; and screening the compounds identified for S8-rRNA binding inhibitory bio-activity.
Another aspect of this invention includes machine-readable media encoded with data representing the coordinates of the three-dimensional structure of the S8 crystal structure alone or in complex with RNA and/or DNA.
In another aspect of the invention provides a composition comprising a S8 rRNA-binding protein from a small ribosomal subunit of Staphylococcus aureus in crystalline form.
In a further aspect of the invention provides S8 protein derived from Staphylococcus aureus and comprising a protein having the coordinates of Table 2 in an essentially pure native form or a homolog thereof. Still further, an aspect of the invention provides a rRNA-binding mode of the protein S8 that is derived from Staphylococcus aureus and comprising a protein having the coordinates of Table 2. In yet another aspect, the invention provides a rRNA-binding function wherein said S8 protein has an rRNA-binding site formed by the amino acids 5-19 forming the N-terminal α-helix with nucleotides A820-A885, and the surface of S8 lined by residues 4-6, 30-32, 56-57, 82-92, 107-111, and 122-125 that interact with nucleotides A587-A758. Another aspect of the invention provides for a heavy atom derivative of a Staphylococcus aureus S8 protein crystal wherein a rRNA-binding function comprises a protein having the coordinates represented in FIGS. 1 and 7 to 14 and listed in Table 2.
In yet another aspect, the invention provides a process of identifying an inhibitor compound capable of inhibiting the rRNA-binding activity of a Staphylococcus aureus S8, said process comprising:
introducing into a suitable computer program information defining an rRNA-binding site conformation of a S8 inhibitor complex molecule comprising a conformation defined by the coordinates of the structures shown in FIGS. 1 and 7 to 14 and listed in Table 2 wherein said program displays the three-dimensional structure thereof;
creating a three dimensional structure of a test compound in said computer program;
displaying and superimposing the model of said test compound on the model of said rRNA-binding site;
assessing whether said test compound model fits spatially into the rRNA-binding site;
incorporating said test compound in a biological rRNA-binding assay for a activity characterized by said rRNA-binding site; and
determining whether said test compound inhibits binding activity in said assay.
In yet another aspect, the invention provides a process of identifying an inhibitor compound capable of inhibiting rRNA-binding activity of a Staphylococcus aureus S8 according to claim 2, said process comprising:
carrying out an in vitro assay by introducing said compound in a biological rRNA-binding assay according to claim 2 and
determining whether said test compound inhibits the ribosomal enzymatic activity or the rRNA-binding function in said assay.
In yet another aspect, the invention provides a product of the process of that is a peptide, peptidomimetic or synthetic molecule and is useful for inhibiting S8-rRNA binding in treatment of bacterial infections in a mammal. In another aspect, the invention provides a product that is a competitive or non-competitive inhibitor of a Staphylococcus aureus S8-rRNA binding activity.
In yet another aspect, the invention provides a process for determining a crystal structure form using structural coordinates of a Staphylococcus aureus S8 crystal or portions thereof, to determine a crystal form of a mutant, homologue or co-complex of said rRNA-binding function by molecular replacement.
In another aspect, the invention provides a process designing drugs useful for inhibiting Staphylococcus aureus S8 activity using atomic coordinates of a Staphylococcus aureus S8 to computationally evaluate a chemical entity for associating with a rRNA-binding site of a Staphylococcus aureus S8.
In yet another aspect, the invention provides a composition comprising a S8 rRNA-binding protein from the small ribosomal subunit of Staphylococcus aureus in orthorhombic crystalline form having a space group of P212121.
A preferred aspect of the invention provides a composition wherein the crystalline form has lattice constants of a=42.1 Å, b=55.9 Å, c=61.3 Å, α=90.0°, β=90.0°, γ=90.0°.
Another preferred aspect of the invention provides a composition wherein a crystalline form contains one Staphylococcus aureus S8 molecule in a asymmetric unit.
In yet another aspect, of the invention provides a S8 protein composition wherein a S8 protein has an active site cavity formed by the amino acids S107, T108, S109, and E126. S8 protein composition is characterised by the coordinates selected from the group consisting of the coordinates of FIGS. 1 and 7 to 14 and Table 2.
Other aspects and advantages of the present invention are described further in the following detailed description of the preferred embodiments thereof.



DESCRIPTION OF THE FIGURES
FIG. 1 provides a representation of a secondary structural element crystal structure of a native S8 form S. aureus. The figures (a) and (b) depict views of S8 related by a rotation of 90° around a vertical axis. The ribbons represent α-helices and the arrows represent β-sheets.
FIG. 2 provides the purification of S. aureus ribosomal protein S8. Lane 1, markers (3.5, 6, 14.4, 21.5, 31, 36.5, 55, 66, 97, 116, 200 kDa, bottom to top, respectively); lane 2, uninduced cell pellet; lane 3, induced cell pellet; lane 4, total cell lysate; lane 5, soluble cell lysate; lane 6, solubilized cellpellet; lane 7, purified S8 protein.
FIG. 3 provides a filter-binding of S. aureus ribosomal protein S8 to wt and ΔA603 H21 RNA, 32P-RNAs were incubated with increasing amounts of S. aureus S8 on ice for 15 minutes, and then filtered and washed. Maximal binding was normalized to 100% in this experiment.
FIG. 4 provides sequence and predicted secondary strucuture of S. aureus helix 21 rRNA (nts 596-659)
FIG. 5 provides a diagrammatic representation of a S8-rRNA scintillation proximity assay.
FIG. 6. Scintillation proximity assay development. (a) SPA signal due to the biotinylated S8 interaction is detected when RNA and protein are incubated together. (b) The SPA signal is specific and represents biologically-relevant interactions between S8 and rRNA.
FIG. 7 provides a representation of critical residues involved in rRNA binding and their position relative to secondary structural elements in a crystal structure of native S8 form S. aureus. The two Figures (a) and (b) depict orthogonal view of the S8 protein.
FIG. 8 provides a representation of the model of S8 from S. aureus bound to rRNA via its “lower” or N-terminal surface. In the model, the rRNA is from a small ribosomal particle of T. thermophilus, S. aureus S8 was superimposed on a corresponding S8 from T thermophilus. 
FIG. 9 provides a representation of a model of S8 from S. aureus bound to rRNA via the N-terminal α-helix. In the model, the helix binds to a major groove of a double stranded rRNA. The rRNA used in the model is from a small ribosomal particle of T. thermophilus, The figures (a) and (b) depict views related by a rotation of 90° around a vertical axis.
FIG. 10 provides a representation of a model of S8 from S. aureus bound to rRNA in an intact ribosomal particle. The model was created by superimposing a S. aureus S8 onto a homologous S8 in a T. thermophilus 30S ribosomal particle structure.
FIG. 11 provides a representation of a molecular surface of S8 from S. aureus. In the model, two surfaces come in contact with the rRNA, they are distinctly marked: the dense stippling (40%) surface corresponds to the N-terminal helix, and the less dense stippling (20%) surface corresponds to the surface located at the N-terminal side of the molecule.
FIG. 12 provides a representation of a relative position of S8 (arrow) in a ribosomal particle (rRNA also indicated by arrows) as it is shown in the structure of a 30S ribosomal particle of T. thermophilus, where three tRNA molecules are bound. S. aureus S8 is expected to bind at the same relative position in the S. aureus ribosome. The Figures (a) and (b) are related by a 180° rotation about the vertical axis.
FIG. 13 provides a Model of T. thermophilus helix 21 rRNA binding to “underside” of S. aureus S8. S8 residues S107, T108, S109, and E126 make contacts with helix 21 nts A642, C643, and G644 (the highly-conserved base triple).
FIG. 14 provides a surface representation of N-terminal region of S. aureus S8. (a) N-terminus (marked with less dense stippling (20%)) is predicted to bind to rRNA in T. thermophilus 30S ribosomal subunit. (b) The surface electrostatic potential is depicted.



DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a S8 from Staphylococcus aureus crystalline structure of the native enzyme.
S8 Protein From Staphylococcus aureus Crystalline Three-dimensional Structure.
Overall Structure
The crystal structures of S8 from Staphylococcus aureus in its native form has been determined and refined to 1.50 Å resolution. The final model includes residues 4-132 and a total of 281 water molecules as in FIG. 1. The polypeptide chain has an α+β fold divided in a somewhat defined two halves of the molecule: two α-helices and three β-strands form the N-terminal half of the molecule, and the C-terminal half is formed by a small helix and three short, anti-parallel strands. The N- and the C-terminus of molecule are located on opposite sides of the S8 molecule and the loop that connects the N- and C-terminal halves of the molecule protrudes into the solvent on the same side of the molecule as the C-terminus and opposite to the largest surface used by S8 to bind the rRNA.
rRNA Binding
Superposition of a S. aureus S8 onto a S8 of the S30 ribosomal subunit of T thermophylus (1FJG) indicates that there are two regions of interaction with the rRNA: the N-terminal helix formed by residues 5-19 inserts into a major groove of a double helix formed by nucleotides A820-A885. The second interacting surface is formed by residues 4-6, 30-32, 56-57, 82-92, 107-111, and 122-125 on the N-terminus side of a molecule that rides on a double helix formed by nucleotides A587-A758. Either of these two contact surfaces could be targets for small molecules that disrupt the interaction; which by affecting S8-rRNA interactions, ribosomal function would be impaired to the extent of being lethal for a bacterum.
Table 2 provides atomic coordinates of native crystal structures of S8 from S. aureus. The amino acid sequence of S8 from S. aureus is provided in SEQ ID No. 1. Small variations in the atomic coordinates shown in Table 2 will occur such as upon refinement of a crystal structure from a different crystal form that will result in a new set of coordinates. The deviation on Cα atoms from the present coordinate set is not expected to substantially exceed a rms of 2.5 Å. Similarly, bond angles and bond lengths will usually vary within a small range.(Engh, R. A., and Huber, R. (1991) Acta Crystallogr. A47, 392-400.), however, the inter-atomic interactions in Table 2 will remain constant, within the experimental error, as will the relative conformation and orientation or positioning of residues in the rRNA-binding site.
Mutants and Derivatives
The invention further provides homologues, co-complexes, mutants and derivatives of the S8 crystal structure of the invention.
The term “homologue” means a protein having at least 30% amino acid sequence identity with a functional domain of S8. Preferably the percentage identity will be 40, or 50%, more preferably 60 or 70% and most preferably 80 or 90%. A 95% identity is most particularly preferred.
The term “co-complex” means the S8 or a mutant or homologue of the S8 in covalent or non-covalent association with a chemical entity or compound.
The term “mutant” refers to the S8 polypeptide, i.e., a polypeptide displaying the biological activity of wild-type S8 activity, characterized by the replacement of at least one active-site amino acid from the wild-type sequence. Such a mutant may be prepared, for example, by expression of the S8 rRNA-binding protein cDNA previously altered in its coding sequence by oligonucleotide-directed mutagenesis.
S8 mutants may also be generated by site-specific incorporation of unnatural amino acids into the S8 protein using the general biosynthetic method of C. J. Noren et al, Science, 244: 182-188 (1989). In this method, the codon encoding the amino acid of interest in wild-type S8 is replaced by a “blank” nonsense codon, TAG, using oligonucleotide-directed mutagenesis. A suppressor directed against this codon is then chemically aminoacylated in vitro with the desired unnatural amino acid. The aminoacylated residue is then added to an in vitro translation system to yield a mutant S8 protein with the site-specific incorporated unnatural amino acid.
Selenocysteine or selenomethionine may be incorporated into wild-type or mutant S8 protein by expression of S8-encoding cDNAs in auxotrophic E. coli strains (W. A. Hendrickson et al, EMBO J., 9 (5): 1665-1672 (1990)) or a normal strain grown in a medium supplemented with appropriate nutrients that will prevent endogenous synthesis of methionine. In either of these methods, the wild-type or mutated undecaprenyl pyrophosphate synthase cDNA may be expressed in a host organism on a growth medium depleted of either natural cysteine or methionine (or both) but enriched in selenocysteine or selenomethionine (or both).
The term “heavy atom derivative” refers to derivatives of S8 produced by chemically modifying a crystal of S8. In practice, a native crystal is treated by immersing it in a solution containing the desired metal salt, or organometallic compound, e.g., lead chloride, gold thiomalate, thimerosal or uranyl acetate, which upon diffusion into the protein crystal can bind to the protein. The location of the bound heavy metal atom site(s) can be determined by X-ray diffraction analysis of the treated crystal. This information, in turn, is used to generate the phase angle information needed to construct a three-dimensional electron density map from that a model of the atomic structure of the enzyme is derived (T. L. Blundel and N. L. Johnson, Protein Crystallography, Academic Press (1976)).
The term “space group” refers to the arrangement of entities (i.e. molecules) throughout the crystal lattice. There are only 132 possible arrangements, each one unique and identified by a symbol. The space group symbol is formed by a letter (P, F, I, C) and numbers with or without subscripts, for example: P21, I222, C212121, etc.
Methods of Identifying Inhibitors of the S8 From Staphylococcus aureus Crystalline Structure
Another aspect of this invention involves a method for identifying inhibitors of S8 protein characterized by the crystal structure described herein, and the inhibitors themselves. The S8 crystal structure of the invention permits the identification of inhibitors of the rRNA-binding activity of a Staphylococcus aureus S8. Such inhibitors may bind to all or a portion of the active site of the S8; or even be competitive, non-competitive, or uncompetitive inhibitors. Once identified and screened for biological activity, these inhibitors may be used therapeutically or prophylactically to block the rRNA-binding activity of a Staphylococcus aureus S8, and thus, inhibit proper assembly of the small ribosomal subunit.
One design approach is to probe the S8 crystal of the invention with molecules composed of a variety of different chemical entities to determine optimal sites for interaction between candidate inhibitors and the rRNA-binding activity of S8. For example, high resolution X-ray diffraction data collected from crystals soaked in or co-crystallized with other molecules allows the determination of where each type of solvent molecule sticks. (J. Travis (1993) Science, 262:1374). Molecules that bind tightly to those sites can then be further modified and synthesized and tested for the ability to inhibit rRNA-binding activity of S8.
The time-dependent analysis of structural changes in S8 protein during its interaction with other molecules is permitted. The reaction intermediates of S8 protein can also be deduced from the reaction product in co-complex with S8 protein. Such information is useful to design improved analogues of S8 protein inhibitors or to design classes of inhibitors based on the reaction intermediates of the S8 protein and binding activity of S8 inhibitor co-complex. This provides a novel route for designing S8 inhibitors with both high specificity and stability.
Another approach made possible by this invention, is to screen computationally small molecule data bases for chemical entities or compounds that can bind in whole, or in part, to the S8 protein. In this screening, the quality of fit of such entities or compounds to the binding site may be judged either by shape complementarity or by estimated interaction energy (E. C. Meng et al, J. Comp. Chem., 13:505-524 (1992)).
Because S8 may crystallize in more than one crystal form, the structure coordinates of S8, or portions thereof, as provided by this invention are particularly useful to solve the structure of those other crystal forms of S8. They may also be used to solve the structure of S8 mutants, S8 co-complexes, or of the crystalline form of any other protein with significant amino acid sequence homology to any functional domain of S8.
One method that may be employed for this purpose is molecular replacement. In this method, the unknown crystal structure, whether it is another crystal form of S8, an S8 mutant, or an S8 co-complex, or the crystal of some other protein with significant amino acid sequence homology to any functional domain of S8, may be determined using the S8 structure coordinates of this invention as provided in Table 2. This method will provide an accurate structural form for the unknown crystal more quickly and efficiently than attempting to determine such information ab initio.
Thus, the S8 structure provided herein permits the screening of molecules and/or the designing of new molecules that bind to the S8 protein structure, particularly at the active site, via the use of computerized evaluation systems. For example, computer modelling systems are available in that the sequence of the S8, and the S8 structure (i.e., atomic coordinates of S8 and/or the atomic coordinate of the active site cavity, bond angles, dihedral angles, distances between atoms in the active site region, etc. as provided by Table 2 herein) may be input. Thus, a machine readable medium may be encoded with data representing the coordinates of Table 2. The computer then generates structural details of the site into that a test compound should bind, thereby enabling the determination of the complementary structural details of said test compound.
More particularly, the design of compounds that bind to or inhibit S8 according to this invention generally involves consideration of two factors. First, the compound must be capable of physically and structurally associating with the S8 protein. Non-covalent molecular interactions important in the association of S8 protein with its ligands include hydrogen bonding, van der Waals and hydrophobic interactions.
Second, the compound must be able to assume a conformation that allows it to associate with S8 protein. Although certain portions of the compound will not directly participate in this association of an S8 protein, those portions may still influence the overall conformation of the molecule. This, in turn, may have a significant impact on potency. Such conformational requirements include the overall three-dimensional structure and orientation of the chemical entity or compound in relation to all or a portion of the binding site, e.g., active site or accessory binding site of S8 protein, or the spacing between functional groups of a compound comprising several chemical entities that directly interact with S8, such as rRNA.
The potential inhibitory or binding effect of a chemical compound on S8 may be analyzed prior to its actual synthesis and testing by the use of computer modelling techniques. If the theoretical structure of the given compound suggests insufficient interaction and association between it and S8, synthesis and testing of the compound is obviated. However, if computer modelling indicates a strong interaction, the molecule may then be synthesized and tested for its ability to bind to S8 and inhibit using a suitable assay. In this manner, synthesis of inoperative compounds may be avoided.
An inhibitory or other binding compound of S8 may be computationally evaluated and designed by means of a series of steps in that chemical entities or fragments are screened and selected for their ability to associate with the individual binding pockets or other areas of S8 protein.
One skilled in the art may use one of several methods to screen chemical entities or fragments for their ability to associate with S8 and more particularly with the individual binding pockets of the S8 active site or accessory binding site. This process may begin by visual inspection of, for example, the active site on the computer screen based on the S8 coordinates in Table 2. Selected fragments or chemical entities may then be positioned in a variety of orientations, or docked, within a binding pocket of S8. Docking may be accomplished using software such as Quanta and Sybyl, followed by energy minimization and molecular dynamics with standard molecular mechanics forcefields, such as CHARMM and AMBER.
Specialized computer programs may also assist in the process of selecting fragments or chemical entities. These include:
1. GRID (P. J. Goodford, “A Computational Procedure for Determining Energetically Favorable Binding Sites on Biologically Important Macromolecules”, J. Med. Chem., 28:849-857 (1985)). GRID is available from Oxford University, Oxford, UK.
2. MCSS (A. Miranker and M. Karplus, “Functionality Maps of Binding Sites: A Multiple Copy Simultaneous Search Method”, Proteins: Structure, Function and Genetics, 11:29-34 (1991)). MCSS is available from Molecular Simulations, Burlington, Mass.
3. AUTODOCK (D. S. Goodsell and A. J. Olsen, “Automated Docking of Substrates to Proteins by Simulated Annealing”, Proteins: Structure, Function, and Genetics, 8:195-202 (1990)). AUTODOCK is available from Scripps Research Institute, La Jolla, Calif.
4. DOCK (I. D. Kuntz et al., “A Geometric Approach to Macromolecule-Ligand Interactions”, J. Mol. Biol., 161:269-288 (1982)). DOCK is available from University of California, San Francisco, Calif.
Additional commercially available computer databases for small molecular compounds includes Cambridge Structural Database, Fine Chemical Database, and CONCORD, for a review see Rusinko, A., Chem. Des. Auto. News 8, 44-47 (1993).
Once suitable chemical entities or fragments have been selected, they can be assembled into a single compound or inhibitor. Assembly may be proceed by visual inspection of the relationship of the fragments to each other on the three-dimensional image displayed on a computer screen in relation to the structure coordinates of S8 protein. This would be followed by manual model building using software such as Quanta or Sybyl.
Useful programs to aid one of skill in the art in connecting the individual chemical entities or fragments include:
1. CAVEAT (P. A. Bartlett et al, “CAVEAT: A Program to Facilitate the Structure-Derived Design of Biologically Active Molecules”, in Molecular Recognition in Chemical and Biological Problems”, Speical Pub., Royal Chem. Soc. 78, pp. 182-196 (1989)]. CAVEAT is available from the University of California, Berkeley, Calif.
2. 3D Database systems such as MACCS-3D (MDL Information Systems, San Leandro, Calif.). This area is reviewed in Y. C. Martin, “3D Database Searching in Drug Design,” J. Med. Chem., 35:2145-2154 (1992).
3. HOOK (available from Molecular Simulations, Burlington, Mass.).
Instead of proceeding to build an S8 protein inhibitor in a step-wise fashion one fragment or chemical entity at a time as described above, inhibitory or other S8 binding compounds may be designed as a whole or “de novo” using either an empty active site or optionally including some portion(s) of a known ligand(s). These methods include:
1. LUDI (H. J. Bohm, “The Computer Program LUDI: A New Method for the De Novo Design of Enzyme Inhibitors”, J. Comp. Aid. Molec. Design, 6:61-78 (1992)). LUDI is available from Biosym Technologies, San Diego, Calif.
2. LEGEND (Y. Nishibata and A. Itai, Tetrahedron, 47:8985 (1991)). LEGEND is available from Molecular Simulations, Burlington, Mass.
3. LEAPFROG (available from Tripos Associates, St. Louis, Mo.).
Other molecular modelling techniques may also be employed in accordance with this invention. See, e.g., N. C. Cohen et al, “Molecular Modeling Software and Methods for Medicinal Chemistry”, J. Med. Chem., 33:883-894 (1990). See also, M. A. Navia and M. A. Murcko, “The Use of Structural Information in Drug Design”, Current Opinions in Structural Biology, 2:202-210 (1992). For example, where the structures of test compounds are known, a model of the test compound may be superimposed over the model of the structure of the invention. Numerous methods and techniques are known in the art for performing this step, any of which may be used. See, e.g., P. S. Farmer, Drug Design, Ariens, E. J., ed., Vol. 10, pp 119-143 (Academic Press, New York, 1980); U.S. Pat. No. 5,331,573; U.S. Pat. No. 5,500,807; C. Verlinde, Structure, 2:577-587 (1994); and I. D. Kuntz, Science, 257:1078-1082 (1992). The model building techniques and computer evaluation systems described herein are not a limitation on the present invention.
Thus, using these computer evaluation systems, a large number of compounds may be quickly and easily examined and expensive and lengthy biochemical testing avoided. Moreover, the need for actual synthesis of many compounds is effectively eliminated.
In another aspect, the S8 structure of the invention permit the design and identification of synthetic compounds and/or other molecules that have a shape complimentary to the conformation of the S8 active site of the invention. Using known computer systems, the coordinates of the S8 structure of the invention may be provided in machine readable form, the test compounds designed and/or screened and their conformations superimposed on the structure of the invention. Subsequently, suitable candidates identified as above may be screened for the desired S8 inhibitory bioactivity, stability, and the like.
Once identified and screened for biological activity, these inhibitors may be used therapeutically or prophylactically to block rRNA-binding activity of S8, and thus, inhibit proper assembly of the small ribosomal subunit.
As used herein the term “natural product molecule” includes all non-synthetic products of nature and includes, but is not limited to, derivatives, extracts or homologs thereof, having, or containing, a bioactive component.
Another aspect of this invention involves a method for identifying inhibitors of a S8 characterized by the crystal structure and rRNA-binding site described herein. The S8 from S. aureus crystalline structure of the invention permits the identification of inhibitors of ribosomal function. Such inhibitors may be competitive, binding to all or a portion of the rRNA-binding site of the S8; or non-competitive and bind to and inhibit ribosomal assembly or function whether or not it is bound to another chemical entity.
One design approach is to probe the S8 crystal of the invention with molecules composed of a variety of different chemical entities to determine optimal sites for interaction between candidate S8 inhibitors and the protein. For example, high resolution X-ray diffraction data collected from crystals saturated with solvent allows the determination of where each type of solvent molecule binds. Small molecules that bind tightly to those sites can then be designed and synthesized and tested for their S8 inhibitor activity.
This invention also enables the development of compounds that can isomerize to short-lived reaction intermediates in the chemical reaction of a substrate or other compound that binds to or with the S8. Thus, the time-dependent analysis of structural changes in the S8 during its interaction with other molecules is permitted. The reaction intermediates of the S8 can also be deduced from the reaction product in co-complex with the S8. Such information is useful to design improved analogues of known S8 inhibitors or to design classes of inhibitors based on the reaction intermediates of the S8-rRNA and S8 inhibitor co-complex. This provides a route for designing S8 inhibitors with both high specificity and stability.
Another approach made possible by this invention is to screen computationally small molecule databases for chemical entities or compounds that can bind in whole, or in part, to the S8 protein. Details on this process and the results it can provide are now documented in the art. For a description of this type of technology please refer to PCT application WO 97/16177 published 09 May 1997; the techniques described there for computer modeling are incorporated herein by reference.
Once identified by the modeling techniques, the inhibitor of ribosomal function may be tested for bio-activity using standard techniques. For example, the structure of the invention may be used in activity assays to determine the inhibitory activity of the compounds or binding assays using conventional formats to screen inhibitors. One particularly suitable assay format includes the enzyme-linked immunosorbent assay (ELISA). Other assay formats may be used; these assay formats are not a limitation on the present invention.
In another aspect, the S8 structure of the invention permit the design and identification of synthetic compounds and/or other molecules that are characterized by the conformation of the S8 of the invention. Using known computer systems, the coordinates of the S8 structure of the invention may be provided in machine readable form, the test compounds designed and/or screened and their conformations superimposed on the structure of the S8 of the invention. Subsequently, suitable candidates identified as above may be screened for the desired inhibitory bio-activity, stability, and the like.
Once identified and screened for biological activity, these inhibitors may be used therapeutically or prophylactically to block S8 function, and thus, overcome bacterial resistance to antibiotics, for example, of the beta-lactam class, eg. imipenem, penicillins, cephalosporins, etc. by using an entirely different mechanism of attacking bacteria in diseases produced by bacterial infection.
The following examples illustrate various aspects of this invention. These examples do not limit the scope of this invention that is defined by the appended claims.
EXAMPLE 1
The Expression and Purification of the S8 From Staphylococcus aureus in Escherichia coli 
The gene for S. aureus S8 was PCR amplified from strain WCUH29 genomic DNA, and the resulting fragment was cloned into pET28a(+) for expression in E. coli. The S. aureus S8-expression construct (S8sa-pET28) was transformed into BL21(DE3) cells for expression and purified by cation exchange chromatography. The soluble polypeptide includes 132 amino acid residues with a molecular weight of 14,830 Da. This product was greater than 95% pure by SDS PAGE, has the desired RNA-binding activity, and N-terminal amino acid analysis confirmed its identity. A one liter culture of E. coli haboring the S8 expression construct was induced with IPTG for three hours at 37° C. FIG. 2 shows that very little of the overexpressed protein was present in the soluble fraction (lane 5). After solubilization of the protein in 6M urea and purification by anion exchange chromatography, the resulting protein appeared to be greater than 95% pure. N-terminal sequencing, MALDI-MS and AA analysis all confirmed the identity of the purified protein.
1.A. Measurement of S8 Activity.
It is also possible to define ligand interactions with S8 in experiments that are not dependent upon enzyme catalyzed turnover of substrates. This type of experiment can be done in a number of ways:
1.B.1. Effects of Ligand Binding Upon Intrinsic Fluorescence (e.g. of Tryptophan).
Binding of either natural ligands or inhibitors may result in the protein's conformational changes that alter its fluorescence. Using stopped-flow fluorescence equipment, this can be used to define the microscopic rate constants that describe binding. Alternatively, steady-state fluorescence titration methods can yield the overall dissociation constant for binding in the same way that these are accessed through enzyme inhibition experiments.
EXAMPLE 2
Crystallization, Structure Determination and Refinement of the Crystal Structure of the S8 from S. aureus 
2.A. Crystallization
Single crystals of native S8 grew from sitting drops prepared by mixing 2 μL protein with 2 μL of reservoir solution containing 30% PEG4000, 0.2M Li2SO4, 0.1M Tis-HCl, pH 8.5. The drops were left to equilibrate at room temperature against 500 μL of the reservoir solution. By registering the position and intensity of many tens of thousands of diffraction spots using the computer program HKL2000 (Otwinowski, Z. and Minor, W. (1996) Methods in Enzymology 276, 307-326) and, program MOSFLM (A. G. W. Leslie, MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK and Collaborative Computational Project, Number 4, (1994) Acta Cryst. D50, 760-763.) the crystal has been determined to be the orthorhombic space group P212121 and have unit cell parameters (lattice constants): a=42.1 Å, b=55.9 Å, c=61.3 Å, alpha=beta=gamma=90.0° and one molecule in the asymmetric unit.
2.B. X-ray Diffraction Data Collection
The crystal was picked up with a loop and frozen by quickly submerging it into liquid nitrogen before mounting it under the cold stream. Diffraction data was collected at CHESS F2 beamline using 1.000 Å wavelength x-rays and the ADSC QuantumIV detector. The data was integrated, reduced and scaled with DPS/MOSFLM/SCALA (CCP4). The data collection statistics are shown in Table 3.
2.C. Structure Determination
The structure was determined by molecular replacement using the program AmoRe (Navaza). and the atomic coordinates of the S8 structure from B. stearothermophylus (1SEI). The solution had a correlation coefficient of 0.50 and R=0.49. The correct amino acid sequence was traced before refinement. The suite of programs CNX was used for the refinement and the interactive graphics program O was used for manipulating the model. The final model includes residue 4 to 132 and 281 water molecules. Residues 1 to 3 are not visible in the electron density map.
2.D. Model Building and Refinement
The electron density map was of high quality and afforded the placement of the complete molecule using the interactive computer graphics program O (Jones, T. A. et al. (1991) Acta Crystallogr. A47: 110-119). The model was refined against diffraction data by successive rounds of simulated annealing with torsion angle dynamics, positional refinement and restrained B-factor refinement using CNX (A. Brunger et al., Science, 235: 458-460 (1987)) followed by manual intervention. The refinement and manual rebuilding was monitored by the quality of the 2Fo-Fc and Fo-Fc electron density maps and the value of the crystallographic R and Rfree. The final R is 0.19 and the Rfree is 0.23 for 23,473 reflections to 1.50 Å resolution. The rms deviation from the reference bond lengths and bond angles (Engh & Huber (1991) Acta Crystallogr. A47: 392-400) are 0.017 Å and 1.8°, respectively. The refined model includes residues 4-132 according to the amino acid sequence SEQ ID NO:1. The N-terminal residues 1 to 3 were disordered in the four molecules. In the refined model, all the main chain conformations fall in the “allowed” regions of the Ramachandran plot. The refinement statistics are shown in Table 4.
EXAMPLE 3
Identifying Inhibitors of Activity of the S. aureus S8 Protein
Avi-tagged S8 was expressed in E. coli along with with BirA (biotin ligase), and LC/MS indicated that approximately 50% of the S8 contained the biotin group at the N-terminus (data not shown). RNA filter-binding studies established that the biotinylated Avi-tagged S8 protein recognized Helix 21 rRNA with an affinity comparable to the untagged protein, Table 5, indicating that the peptide tag and subsequent labeling have no adverse effect on RNA-protein recognition. This biotinylated protein was then used to develop a high throughput-screening assay, which will be used to detect inhibitors of the S8-rRNA interaction. The basis of the scintillation proximity assay is shown in FIG. 5. Essentially, the Helix 21 rRNA fragment is labeled with 33P or 3H (either internally or at the -3′ or 5′-ends), and a complex is allowed to form with the biotinylated S8 protein. After formation of the RNA-protein complex, streptavidin SPA beads (Amersham Pharmacia) are added and incubated with the RNA-protein complex, and the samples are read in a microplate scintillation counter (eg, TopCount by Packard). Using biotinylated (Avi-tagged) S. aureus ribosomal protein S8, 33P-labeled helix 21 RNA, and streptavidin SPA beads, a specific signal due to protein-RNA binding was detected, FIG. 6(a). When Helix 21 ΔA649 substrate was used in the SPA assay, no signal above background could be detected, indicating the validity of the SPA format as a viable assay to examine S8-rRNA interactions, FIG. 6(b). The specificity of S8-rRNA recognition was further validated in the SPA format by titrating the binding reactions with unlabeled cognate and non-cognate RNAs. Results show that the addition of excess, unlabeled, wild-type Helix 21 RNA competes the SPA signal to near background levels, while the addition of like amounts of Helix 21 ΔA649 RNA does not (data not shown). This further indicates that the SPA format reflects true recognition of 16S rRNA by S8 protein. This assay can be transferred to a multi-well format (example, 96- or 384-well microplates) for high throughput screening of diverse compound collections. Such compounds that inhibit the S8-rRNA interaction may be useful anti-bacterials.
3.A. Cloning of S. aureus S8
The gene for S. aureus S8 was PCR amplified from strain WCUH29 genomic DNA using a forward primer containing a BspHI site (5′-ACTTC CTCATGACAATGACAGATCCAATCG-3′) (SEQ ID NO: 3) and a reverse primer containing a HindIII site (5′-CTTCTCAAGCTTTTACCAAACGTATGCGATAA-3′) (SEQ ID NO: 4). The 419bp fragment was digested with BspHI and HindIII, purified, and ligated into pET28a(+) cut with NcoI and HindIII. Positive transformants were confirmed by sequencing.
3.B. pET24-AviTag Vector Construction
A linker was made encoding the AviTag (Avidity, see below) with an NdeI 5′ overhang, 3′ BamHI overhang and containing a unique ScaI site after the tag. This was ligated into pET24b(+) from Novagen cut with NdeI and BamHI.









5′T ATG GCT GGT GGC CTG AAC GAT ATT TTC GAA GCT CAG
(SEQ ID NO: 5)



3′   AC CGA CCA CCG GAC TTG CTA TAA AAG CTT CGA GTC
(SEQ ID NO: 6)


     M   A   G   G   L   N   D   I   F   E   A   Q
(SEQ ID NO: 7)


 


AAA ATC GAA TGG CAT GAA AGT ACT G   3′


TTT TAG CTT ACC GTA CTT TCA TGA C CTA G 5′


 K   I   E   W   H   E   S






3.C. Cloning of AviTag-S8 Construct

The intact S. aureus S8 gene was PCR amplified from WCUH29 genomic DNA using Pwo polymerase (Roche) and the following primers: forward (5′-ATGACAATGACAGATCCAATCGC-3′) (SEQ ID NO: 8) and reverse (5′-TTTACCAAACGTATGCGATAATTTC-3′) (SEQ ID NO: 9). The 400 bp fragment was kinased and ligated into pET24-AviTag digested with ScaI and dephosphorylated. The construct was confirmed by sequencing and transformed into BL21 (DE3) cells containing pACYCbirA (Avidity) for expression of the biotinylated-AviTag-S8.
3.D. Protein Expression and Purification
The S. aureus S8-expression construct (S8sa-pET28) was transformed into BL21(DE3) cells for expression and a 10 ml overnight culture in LB, 50 ug/ml Kanamycin, 1% glucose was diluted 1:100 and grown to an OD600 of 0.55. IPTG was added to 0.5 mM and induction carried out for 3 h at 37° C. Cells were lysed in 30ml (5 ml/g wet weight) of 50 mM Na-phosphate pH 7.5 and lysed via sonication and freeze/thaw. After centrifugation, the pellet was solubilized in 30 ml of 6M Urea/20 mM Tris pH 7.0 (Buffer A) and the filtered supernatant applied to a 5 ml HiTrap SP column. S8 was eluted with a 40 column volume gradient of 0-1M NaCl in Buffer A. Fractions containing S8 were pooled and refolded by dialysis against several changes of 80 mM Hepes pH 7.6 and 1M KCl. Aliquots were frozen in a dry ice/ethanol bath and stored at −80° C. Integrity of the protein was confirmed by N-terminal sequencing, MALDI-MS and AA analysis. Yield from the 1 liter culture was 36 mg of purified protein.
3.E. Expression and Purification of B-Avi-S8
5 ml of an overnight LB/Kanamycin (50 ug/ml)/Chloramphenicol (34 ug/ml)/1% glucose culture was diluted 100-fold into media containing 50 uM biotin. The culture was grown at 37° C./250 rpm to an OD600 of 0.5, IPTG was added to 0.5 mM and growth continued at 37° C. for an additional 3 h. Pelleted cells were homogenized in 6M Urea/20 mM Tris pH7.0 (BufferA) in a volume of 5 ml/g cells. Clarified lysate was applied to a 5 ml HiTrapSP column (Amersham Pharmacia) and eluted with a 40 column volume gradient of 0-1M NaCl in BufferA. Fractions containing B-Avi-S8 were pooled and dialized at 4° C. against 80 mM Hepes pH 7.6/1M KCl. Aliquots were quick-frozen and stored at −80° C. N-terminal sequencing, LC/MS and AA analysis confirm the integrity of the protein. Yield was 14 mg of greater than 90% purity from a 500 ml culture with  ̃50% biotinylation.
3.F. Cloning and Transcription of Helix 21 rRNAs
A DNA fragment corresponding to Helix 21 (nts 584-655) of E. coli 16S rRNA was amplified by PCR of E. coli genomic DNA. A T7-promoter sequence was incorporated into the fragment by the 5′-primer, and the fragment was cloned into the EcoRI-KpnI sites of pUC19 to generate pUC-EcH21. Helix 21 from Staphylococcus aureus (corresponding to nts 596-659 of 16S rRNA) was cloned downstream of a T7 promoter in a similar manner to generate the plasmid pUC-SaH21. The generation of mutant derivatives of S. aureus Helix 21 was done by incorporation of site directed mutagenesis of PCR primers. Unlabeled RNAs were trancribed from BamHI-linearized DNA templates using MEGAshortscript kit (Ambion Inc., Austin, Tex.). RNA substrates for filter-binding studies were made by end-labeling with γ-32P or 33P-ATP.
3.G. Filter-binding
For filter-binding experiments, labeled RNAs were renatured by preincubation in binding buffer (80 mM HEPES-KOH pH 7.6, 350 mM KOAc, 20 mM MgOAc) for fifteen minutes at 40° C. Renatured RNA was then mixed with the appropriate amount of protein and then incubated for fifteen minutes on ice and then filtered immediately on 0.45 μM nitrocellulose filters (Whatman), washed with 1.0 ml of binding buffer, and then counted in a scintillation counter. Kd's were determined from several independent binding experiments for each substrate RNA.
3.H. Characterisation of the RNA-binding Activity of S. aureus S8
In order to characterise the RNA-binding activity of S. aureus S8, an RNA-filter-binding assay was developed. The results of these experiments, shown in FIG. 3, demonstrate that the interaction of S8 with wild-type Helix 21 RNA has a measured affinity of approximately 400 nM. This interaction is highly specific, in that an RNA containing a deletion of A603 fails to demonstrate any appreciable binding by S8. This result also highlights the importance of the base triple within helix 21, as A603 is predicted to interact with the A604-U652 basepair.
Several mutations were introduced into Helix 21 rRNA, shown in FIG. 4, and the apparent dissociation constants for the interaction of S8 and these variant RNA substrates was examined. These results are shown in Table 5. Substitution of the A-U base pair (nts 604-652) with G-C result in a tenfold decrease in binding affinity. This nucleotide substitution is predicted to maintain the stem structure in this region but it changes the primary sequence of the RNA. Since S8 still binds to this RNA, albeit at a tenfold decreased affinity, this underscores the fact that while maintenance of the secondary structure in this region is required, the exact sequence of the RNA is necessary for optimal recognition by S8. Deletion of A649, and substitutions of C651-U and A650C651-U all result in the complete abrogation of binding by S8, suggesting the critical importance of nucleotides in this region. The conserved nature of this RNA-protein recognition is further demonstrated by the fact that S. aureus S8 can recognize E. coli Helix 21 rRNA with a similar affinity as with S. aureus Helix 21 rRNA.
EXAMPLE 4
Modeling Studies of S. aureus S8-rRNA Binding
Superposition of the S. aureus S8 onto the S8 in the S30 ribosomal subunit of T thermophilus (1FJG), shown in FIG. 12(a), indicates that there are two regions of interaction with the rRNA: residues 5-19 (N-terminal α-helix) with nucleotides A820-A885 and residues 4-6, 30-32, 56-57, 82-92, 107-111, and 122-125 with nucleotides A587-A758. This second RNA-interacting face is in direct contact with bases and more likely the surface to target with inhibitors that disrupt the S8-rRNA interaction(s).
The surface representation of S. aureus S8 protein is shown in FIG. 14(a). The N-terminus, marked with less dense stippling (20%), is the region predicted to bind to rRNA in T. thermophylus S30 ribosomal particle and presumably also in S. aureus where it rides on the rRNA formed by a double stranded stem structure formed by nucleotides A587 to A758 in 1FJG. In FIG. 14(b), the calculated surface electrostatic potential shows that the S8-rRNA interactions are not predominantly electrostatic. In this interacting surfaces there appears to be cavities between protein and the rRNA that may accommodate drug(s) that could interfere with the normal S8-rRNA interaction.
FIG. 13 shows a model of T. thermophilus helix 21 rRNA binding to the “underside” of S. aureus S8. S8 residues S107, T108, S109, and E126 make contacts with helix 21 nts A642, C643, and G644 (the highly-conserved base triple). This modeling data is consistent with the biochemical data showing that nucleotides in this base triple are critical for accurate recognition by S. aureus S8 as shown in Table 5.

















TABLE 1





E.
H.
P.
M.
S.
B.
S.
S.
E.




coli
influenzae
aeruginosa
catarrhalis
aureus
subtilis
pneumoniae
pyogenes
faecalis
Human

























100
84
62
58
48
47
47
45
47
23
E. coli



100
62
63
45
45
45
45
45
22
H. influenzae




100
56
43
46
45
42
45
24
P. aeruginosa





100
46
46
45
46
47
23
M. catarrhalis






100
77
74
78
77
22
S. aureus







100
72
77
81
27
B. subtilis








100
91
80
29
S. pneumoniae









100
84
26
S. pyogenes










100
27
E. faecalis











100
Human
















TABLE 3







Data collection statistics











Resolution, Å
Complete, %
Multiplicity
I/σ<I>
Rsym














4.74
95.8
2.7
14.6
0.040


3.35
99.3
3.0
17.2
0.035


2.74
99.8
3.1
14.6
0.037


2.37
99.9
3.2
11.9
0.051


2.12
99.9
3.2
9.1
0.068


1.94
100.0
3.2
8.3
0.077


1.79
100.0
3.2
5.8
0.115


1.68
100.0
3.2
4.3
0.155


1.58
99.7
3.1
3.1
0.213


1.50
97.5
2.7
2.5
0.274



99.4
3.1
8.4
0.053
















TABLE 4





Refinement statistics


















Resolution
20-1.5Å



No. Reflections
23,473



Completeness
99.2%



R
0.19



Rfree
0.23



No. protein atoms
1049



No. solvent atoms
281



rms deviation from ideal:



bond length
0.017Å



bond angle
1.8°










Table 2. Atomic Coordinates of the Native S8 Structure (SEQ ID NO:1)

Legend:

    1. Under the heading ATOM appears a “atom number” (e.g. 1,2,3,4 . . . etc) and the “atom name” (e.g. CA, CB, N, . . . etc) such that to each “atom name” in the coordinate list corresponds an “atom number”.
    2. Under the heading RESIDUE appears a three-letter “residue name” (e.g THR, ASP, etc), a “chain identifier” represented by a capital letter (e.g. A, B, C D, etc) and a “residue number”, such that to each residue (or amino acid) in the amino acid sequence of the particular protein in the structure corresponds a name that identifies it, a number according to its position along the amino acid sequence, and a chain name. The chain name identifies a particular molecule in the crystal structure. For instance, if there are more than one molecule that form the unit that is repeated throughout the crystal lattice, then each unit is identified as molecule A, or molecule B, or molecule C, etc
    3. Under the headings X, Y, or Z appear the Cartesian coordinates of the atoms in the structure
    4. Under the heading OCC appears the “occupancy factor” for each atom. If the entity is present and observed in the structure then an occupancy of 1.00 is assigned to it. If the atom is present but not observed, an occupancy of 0.00 is assigned to it. Also, factors between 0.00 and 1.00 are also acceptable and represent the degree of confidence in observing that atom a that particular position.
    5. Under the heading B appears the “B-factor” or “temperature factor” that can adopt, in principle, any value. It is meant to represent the atomic displacement around that position. Atomic coordinates of the native S8 structure (SEQ ID NO:1)












Atomic coordinates of the native S8 structure


CRYST1 42.100 55.500 61.400 90.00 90.00 90.00















ATOM
RESIDUE

X
Y
Z
Occ
B




















1
CB
THR
A
4
−6.461
24.691
−0.181
1.00
42.83



2
OG1
THR
A
4
−5.711
24.797
−1.400
1.00
45.08


3
CG2
THR
A
4
−7.614
23.708
−0.339
1.00
45.36


4
C
THR
A
4
−5.729
26.957
0.416
1.00
33.79


5
O
THR
A
4
−5.382
27.840
−0.383
1.00
33.22


6
N
THR
A
4
−7.982
26.637
−0.747
1.00
37.31


7
CA
THR
A
4
−6.977
26.097
0.220
1.00
39.29


8
N
ASP
A
5
−5.025
26.661
1.495
1.00
23.47


9
CA
ASP
A
5
−3.817
27.419
1.821
1.00
17.33


10
CB
ASP
A
5
−4.144
28.279
3.011
1.00
15.38


11
CG
ASP
A
5
−2.929
29.006
3.517
1.00
14.79


12
OD1
ASP
A
5
−1.887
28.833
2.888
1.00
15.80


13
OD2
ASP
A
5
−3.079
29.711
4.494
1.00
14.90


14
C
ASP
A
5
−2.759
26.362
2.147
1.00
16.58


15
O
ASP
A
5
−2.704
25.870
3.281
1.00
18.05


16
N
PRO
A
6
−1.903
26.000
1.177
1.00
16.44


17
CD
PRO
A
6
−1.858
26.464
−0.226
1.00
20.90


18
CA
PRO
A
6
−0.887
24.971
1.423
1.00
17.38


19
CB
PRO
A
6
−0.116
24.882
0.115
1.00
19.60


20
CG
PRO
A
6
−1.151
25.310
−0.906
1.00
24.25


21
C
PRO
A
6
0.037
25.237
2.573
1.00
16.97


22
O
PRO
A
6
0.526
24.286
3.214
1.00
14.81


23
N
ILE
A
7
0.313
26.514
2.830
1.00
13.93


24
CA
ILE
A
7
1.212
26.837
3.939
1.00
12.98


25
CB
ILE
A
7
1.682
28.282
3.865
1.00
13.39


26
CG2
ILE
A
7
2.495
28.601
5.156
1.00
13.95


27
CG1
ILE
A
7
2.574
28.470
2.624
1.00
16.70


28
CD1
ILE
A
7
2.955
29.946
2.375
1.00
17.46


29
C
ILE
A
7
0.489
26.529
5.247
1.00
14.00


30
O
ILE
A
7
1.106
25.894
6.120
1.00
14.04


31
N
ALA
A
8
−0.761
26.953
5.427
1.00
14.80


32
CA
ALA
A
8
−1.482
26.605
6.644
1.00
13.39


33
CB
ALA
A
8
−2.869
27.199
6.629
1.00
13.83


34
C
ALA
A
8
−1.565
25.053
6.751
1.00
13.55


35
O
ALA
A
8
−1.446
24.453
7.843
1.00
15.03


36
N
ASP
A
9
−1.791
24.363
5.635
1.00
15.10


37
CA
ASP
A
9
−1.858
22.908
5.763
1.00
17.82


38
CB
ASP
A
9
−2.198
22.262
4.410
1.00
18.75


39
CG
ASP
A
9
−3.558
22.657
3.887
1.00
21.83


40
OD1
ASP
A
9
−4.455
23.107
4.646
1.00
25.74


41
OD2
ASP
A
9
−3.736
22.501
2.654
1.00
28.91


42
C
ASP
A
9
−0.533
22.332
6.276
1.00
14.90


43
O
ASP
A
9
−0.542
21.378
7.067
1.00
16.11


44
N
MET
A
10
0.597
22.861
5.827
1.00
13.05


45
CA
MET
A
10
1.906
22.383
6.285
1.00
14.46


46
CB
MET
A
10
3.071
23.090
5.575
1.00
13.13


47
CG
MET
A
10
4.441
22.738
6.164
1.00
12.70


48
SD
MET
A
10
5.626
23.707
5.172
1.00
15.11


49
CE
MET
A
10
7.153
23.070
5.887
1.00
13.64


50
C
MET
A
10
2.043
22.644
7.773
1.00
12.35


51
O
MET
A
10
2.446
21.742
8.503
1.00
13.00


52
N
LEU
A
11
1.741
23.853
8.222
1.00
13.28


53
CA
LEU
A
11
1.883
24.174
9.640
1.00
11.41


54
CB
LEU
A
11
1.444
25.617
9.913
1.00
10.89


55
CG
LEU
A
11
2.303
26.671
9.158
1.00
11.59


56
CD1
LEU
A
11
1.757
28.056
9.614
1.00
12.36


57
CD2
LEU
A
11
3.809
26.562
9.385
1.00
14.75


58
C
LEU
A
11
1.029
23.226
10.476
1.00
13.64


59
O
LEU
A
11
1.471
22.766
11.515
1.00
13.28


60
N
THR
A
12
−0.192
22.948
10.024
1.00
11.82


61
CA
THR
A
12
−1.082
22.038
10.735
1.00
12.04


62
CB
THR
A
12
−2.473
22.064
10.085
1.00
13.84


63
OG1
THR
A
12
−3.033
23.348
10.333
1.00
15.75


64
CG2
THR
A
12
−3.388
21.020
10.697
1.00
19.14


65
C
THR
A
12
−0.548
20.628
10.749
1.00
13.77


66
O
THR
A
12
−0.651
19.923
11.768
1.00
14.02


67
N
ARG
A
13
−0.018
20.151
9.633
1.00
14.34


68
CA
ARG
A
13
0.569
18.795
9.623
1.00
15.56


69
CB
ARG
A
13
1.106
18.446
8.216
1.00
17.77


70
CG
ARG
A
13
0.003
18.123
7.182
1.00
20.88


71
CD
ARG
A
13
−0.743
16.827
7.511
1.00
25.58


72
NE
ARG
A
13
0.198
15.737
7.751
0.75
27.19


73
CZ
ARG
A
13
1.008
15.198
6.833
1.00
29.03


74
NH1
ARG
A
13
1.006
15.633
5.580
1.00
33.07


75
NH2
ARG
A
13
1.846
14.232
7.186
1.00
31.78


76
C
ARG
A
13
1.708
18.724
10.658
1.00
13.44


77
O
ARG
A
13
1.784
17.737
11.426
1.00
14.13


78
N
VAL
A
14
2.564
19.762
10.721
1.00
12.16


79
CA
VAL
A
14
3.683
19.767
11.669
1.00
14.68


80
CB
VAL
A
14
4.629
20.954
11.397
1.00
11.85


81
CG1
VAL
A
14
5.649
21.137
12.586
1.00
12.44


82
CG2
VAL
A
14
5.380
20.736
10.084
1.00
12.20


83
C
VAL
A
14
3.120
19.855
13.087
1.00
11.52


84
O
VAL
A
14
3.578
19.108
13.967
1.00
12.95


85
N
ARG
A
15
2.098
20.672
13.301
1.00
11.56


86
CA
ARG
A
15
1.503
20.856
14.621
1.00
10.79


87
CB
ARG
A
15
0.346
21.843
14.578
1.00
11.82


88
CG
ARG
A
15
−0.211
22.232
15.946
1.00
11.89


89
CD
ARG
A
15
−1.464
23.174
15.884
1.00
13.82


90
NE
ARG
A
15
−1.098
24.376
15.121
1.00
14.40


91
CZ
ARG
A
15
−1.509
24.660
13.888
1.00
16.35


92
NH1
ARG
A
15
−2.346
23.837
13.259
1.00
15.77


93
NH2
ARG
A
15
−1.028
25.719
13.210
1.00
14.51


94
C
ARG
A
15
0.958
19.529
15.132
1.00
10.68


95
O
ARG
A
15
1.215
19.125
16.273
1.00
13.61


96
N
ASN
A
16
0.240
18.827
14.253
1.00
12.18


97
CA
ASN
A
16
−0.346
17.556
14.661
1.00
15.25


98
CB
ASN
A
16
−1.341
17.080
13.590
1.00
16.21


99
CG A
ASN
A
16
−2.549
18.008
13.398
0.50
18.74


100
CG B
ASN
A
16
−1.824
15.676
13.859
0.50
20.66


101
OD1A
ASN
A
16
−3.286
17.894
12.397
0.50
20.74


102
OD1B
ASN
A
16
−1.176
14.706
13.455
0.50
21.76


103
ND2A
ASN
A
16
−2.772
18.898
14.336
0.50
18.12


104
ND2B
ASN
A
16
−2.953
15.556
14.570
0.50
18.81


105
C
ASN
A
16
0.711
16.475
14.903
1.00
13.65


106
O
ASN
A
16
0.619
15.702
15.912
1.00
15.21


107
N
ALA
A
17
1.728
16.355
14.032
1.00
13.10


108
CA
ALA
A
17
2.773
15.354
14.192
1.00
14.08


109
CB
ALA
A
17
3.758
15.372
12.963
1.00
13.25


110
C
ALA
A
17
3.571
15.588
15.463
1.00
12.71


111
O
ALA
A
17
3.954
14.630
16.129
1.00
12.71


112
N
ASN
A
18
3.809
16.866
15.795
1.00
11.25


113
CA
ASN
A
18
4.544
17.266
16.992
1.00
12.37


114
CB
ASN
A
18
4.745
18.804
16.933
1.00
12.25


115
CG
ASN
A
18
5.595
19.334
18.082
1.00
11.43


116
OD1
ASN
A
18
6.644
18.759
18.401
1.00
13.81


117
ND2
ASN
A
18
5.148
20.396
18.705
1.00
13.40


118
C
ASN
A
18
3.726
16.858
18.230
1.00
10.83


119
O
ASN
A
18
4.291
16.311
19.197
1.00
11.44


120
N
MET
A
19
2.421
17.120
18.179
1.00
12.24


121
CA
MET
A
19
1.553
16.767
19.300
1.00
12.44


122
CB
MET
A
19
0.111
17.135
18.992
1.00
12.44


123
CG
MET
A
19
−0.835
16.721
20.145
1.00
13.33


124
SD
MET
A
19
−2.536
17.145
19.741
1.00
18.49


125
CE
MET
A
19
−2.867
15.921
18.627
1.00
20.10


126
C
MET
A
19
1.632
15.281
19.608
1.00
13.50


127
O
MET
A
19
1.740
14.873
20.782
1.00
13.60


128
N
VAL
A
20
1.538
14.452
18.562
1.00
12.37


129
CA
VAL
A
20
1.579
12.989
18.807
1.00
13.21


130
CB
VAL
A
20
0.656
12.247
17.810
1.00
15.22


131
CG1
VAL
A
20
−0.730
12.812
17.910
1.00
14.43


132
CG2
VAL
A
20
1.255
12.328
16.378
1.00
16.73


133
C
VAL
A
20
2.977
12.382
18.868
1.00
16.11


134
O
VAL
A
20
3.177
11.144
18.847
1.00
19.83


135
N
ARG
A
21
3.989
13.256
18.917
1.00
13.57


136
CA
ARG
A
21
5.382
12.881
19.060
1.00
14.55


137
CB
ARG
A
21
5.621
12.188
20.422
1.00
14.10


138
CG
ARG
A
21
5.330
13.146
21.572
1.00
10.31


139
CD A
ARG
A
21
5.546
12.449
22.926
0.50
9.37


140
CD B
ARG
A
21
5.543
12.473
22.941
0.50
13.63


141
NE A
ARG
A
21
5.322
13.318
24.071
0.50
5.45


142
NE B
ARG
A
21
5.749
13.534
23.896
0.50
20.38


143
CZ A
ARG
A
21
6.249
14.148
24.541
0.50
7.97


144
CZ B
ARG
A
21
6.905
14.178
24.000
0.50
17.62


145
NH1A
ARG
A
21
7.438
14.232
23.955
0.50
11.73


146
NH1B
ARG
A
21
7.938
13.839
23.243
0.50
16.00


147
NH2A
ARG
A
21
6.001
14.869
25.591
0.50
13.99


148
NH2B
ARG
A
21
6.999
15.205
24.787
0.50
9.14


149
C
ARG
A
21
5.929
11.985
17.950
1.00
19.18


150
O
ARG
A
21
6.742
11.110
18.212
1.00
19.79


151
N
HIS
A
22
5.490
12.236
16.714
1.00
17.02


152
CA
HIS
A
22
6.034
11.468
15.596
1.00
18.66


153
CB
HIS
A
22
5.294
11.744
14.280
1.00
19.15


154
CG
HIS
A
22
3.964
11.071
14.152
1.00
20.64


155
CD2
HIS
A
22
2.849
11.436
13.473
1.00
24.91


156
ND1
HIS
A
22
3.648
9.905
14.816
1.00
30.45


157
CE1
HIS
A
22
2.394
9.585
14.559
1.00
29.06


158
NE2
HIS
A
22
1.884
10.498
13.749
1.00
33.58


159
C
HIS
A
22
7.508
11.849
15.369
1.00
19.73


160
O
HIS
A
22
7.941
13.005
15.558
1.00
17.77


161
N
GLU
A
23
8.270
10.888
14.855
1.00
19.88


162
CA
GLU
A
23
9.664
11.113
14.541
1.00
20.11


163
CB
GLU
A
23
10.358
9.768
14.260
1.00
27.37


164
CG
GLU
A
23
11.815
9.905
13.819
1.00
30.59


165
CD
GLU
A
23
12.429
8.591
13.293
1.00
40.76


166
OE1
GLU
A
23
11.709
7.766
12.678
1.00
43.53


167
OE2
GLU
A
23
13.651
8.408
13.481
1.00
47.87


168
C
GLU
A
23
9.729
11.975
13.274
1.00
16.44


169
O
GLU
A
23
10.616
12.791
13.138
1.00
16.55


170
N
LYS
A
24
8.774
11.760
12.380
1.00
16.86


171
CA
LYS
A
24
8.785
12.509
11.109
1.00
19.29


172
CB
LYS
A
24
9.759
11.818
10.132
1.00
21.65


173
CG
LYS
A
24
9.201
10.533
9.541
1.00
28.20


174
CD
LYS
A
24
10.257
9.774
8.783
1.00
31.38


175
CE
LYS
A
24
11.155
9.031
9.726
0.50
33.74


176
NZ
LYS
A
24
11.650
9.926
10.809
0.50
33.81


177
C
LYS
A
24
7.408
12.562
10.493
1.00
17.40


178
O
LYS
A
24
6.445
11.905
10.940
1.00
18.36


179
N
LEU
A
25
7.305
13.356
9.425
1.00
16.29


180
CA
LEU
A
25
6.086
13.453
8.672
1.00
17.35


181
CB
LEU
A
25
5.117
14.499
9.247
1.00
17.32


182
CG
LEU
A
25
5.595
15.954
9.132
1.00
16.73


183
CD1
LEU
A
25
4.366
16.848
9.061
1.00
21.28


184
CD2
LEU
A
25
6.520
16.367
10.286
1.00
19.12


185
C
LEU
A
25
6.467
13.805
7.228
1.00
16.64


186
O
LEU
A
25
7.582
14.278
6.964
1.00
16.92


187
N
GLU
A
26
5.557
13.491
6.322
1.00
18.27


188
CA
GLU
A
26
5.785
13.801
4.903
1.00
18.14


189
CB
GLU
A
26
5.813
12.499
4.063
1.00
17.91


190
CG
GLU
A
26
7.116
11.762
4.199
1.00
24.85


191
CD
GLU
A
26
7.103
10.438
3.491
1.00
29.39


192
OE1
GLU
A
26
6.263
10.245
2.563
1.00
30.78


193
OE2
GLU
A
26
7.946
9.602
3.879
1.00
35.10


194
C
GLU
A
26
4.660
14.652
4.429
1.00
16.57


195
O
GLU
A
26
3.523
14.477
4.840
1.00
22.49


196
N
LEU
A
27
4.956
15.625
3.564
1.00
16.18


197
CA
LEU
A
27
3.917
16.450
3.000
1.00
19.66


198
CB
LEU
A
27
3.661
17.706
3.869
1.00
22.81


199
CG
LEU
A
27
4.884
18.573
4.237
1.00
25.00


200
CD1
LEU
A
27
4.664
19.914
3.610
1.00
22.75


201
CD2
LEU
A
27
5.029
18.750
5.734
1.00
28.32


202
C
LEU
A
27
4.323
16.842
1.571
1.00
17.53


203
O
LEU
A
27
5.495
16.802
1.239
1.00
19.86


204
N
PRO
A
28
3.349
17.237
0.736
1.00
20.65


205
CD
PRO
A
28
1.927
17.491
1.004
1.00
20.94


206
CA
PRO
A
28
3.704
17.621
−0.645
1.00
20.41


207
CB
PRO
A
28
2.361
18.010
−1.258
1.00
23.88


208
CG
PRO
A
28
1.321
17.286
−0.347
1.00
27.18


209
C
PRO
A
28
4.673
18.799
−0.653
1.00
20.38


210
O
PRO
A
28
4.556
19.748
0.129
1.00
19.44


211
N
ALA
A
29
5.603
18.790
−1.593
1.00
18.16


212
CA
ALA
A
29
6.564
19.853
−1.704
1.00
21.72


213
CB
ALA
A
29
7.848
19.311
−2.300
1.00
19.37


214
C
ALA
A
29
6.108
21.022
−2.553
1.00
18.53


215
O
ALA
A
29
5.245
20.890
−3.436
1.00
18.27


216
N
SER
A
30
6.626
22.190
−2.201
1.00
18.34


217
CA
SER
A
30
6.449
23.411
−3.047
1.00
16.19


218
CB
SER
A
30
5.183
24.209
−2.727
1.00
20.14


219
OG
SER
A
30
5.339
24.974
−1.529
1.00
21.32


220
C
SER
A
30
7.708
24.222
−2.777
1.00
15.57


221
O
SER
A
30
8.472
23.997
−1.798
1.00
18.05


222
N
ASN
A
31
7.994
25.191
−3.642
1.00
17.71


223
CA
ASN
A
31
9.196
25.960
−3.419
1.00
15.27


224
CB
ASN
A
31
9.347
27.009
−4.532
1.00
15.19


225
CG
ASN
A
31
9.730
26.380
−5.894
1.00
19.59


226
OD1
ASN
A
31
10.574
25.451
−5.969
1.00
21.13


227
ND2
ASN
A
31
9.134
26.918
−6.969
1.00
18.82


228
C
ASN
A
31
9.208
26.685
−2.050
1.00
14.86


229
O
ASN
A
31
10.204
26.632
−1.334
1.00
17.77


230
N
ILE
A
32
8.101
27.357
−1.743
1.00
19.65


231
CA
ILE
A
32
8.001
28.096
−0.485
1.00
15.20


232
CB A
ILE
A
32
6.812
29.111
−0.495
0.50
17.15


233
CB B
ILE
A
32
6.701
28.953
−0.500
0.50
14.78


234
CG2A
ILE
A
32
5.490
28.426
−0.375
0.50
19.36


235
CG2B
ILE
A
32
5.468
28.112
−0.368
0.50
23.40


236
CG1A
ILE
A
32
7.040
30.127
0.644
0.50
18.07


237
CG1B
ILE
A
32
6.797
29.987
0.609
0.50
21.16


238
CD1A
ILE
A
32
6.228
31.417
0.520
0.50
15.99


239
CD1B
ILE
A
32
7.978
30.835
0.383
0.50
19.15


240
C
ILE
A
32
7.989
27.143
0.727
1.00
16.46


241
O
ILE
A
32
8.619
27.437
1.757
1.00
15.29


242
N
LYS
A
33
7.332
25.998
0.591
1.00
17.77


243
CA
LYS
A
33
7.309
25.048
1.743
1.00
16.20


244
CB
LYS
A
33
6.261
23.944
1.526
1.00
13.11


245
CG
LYS
A
33
4.798
24.446
1.720
1.00
14.90


246
CD
LYS
A
33
3.750
23.335
1.630
1.00
15.37


247
CE
LYS
A
33
3.503
22.844
0.200
1.00
18.69


248
NZ
LYS
A
33
2.494
21.745
0.216
1.00
22.36


249
C
LYS
A
33
8.715
24.549
2.031
1.00
18.54


250
O
LYS
A
33
9.101
24.325
3.200
1.00
16.33


251
N
LYS
A
34
9.521
24.317
0.983
1.00
17.44


252
CA
LYS
A
34
10.901
23.930
1.190
1.00
15.42


253
CB
LYS
A
34
11.526
23.571
−0.171
1.00
19.61


254
CG
LYS
A
34
12.900
23.000
−0.095
1.00
26.10


255
CD
LYS
A
34
13.498
22.704
−1.485
1.00
29.86


256
CE
LYS
A
34
12.682
21.719
−2.274
1.00
27.95


257
NZ
LYS
A
34
13.503
21.212
−3.424
1.00
38.16


258
C
LYS
A
34
11.690
25.047
1.883
1.00
17.26


259
O
LYS
A
34
12.504
24.778
2.749
1.00
16.84


260
N
GLU
A
35
11.505
26.317
1.492
1.00
14.62


261
CA
GLU
A
35
12.208
27.398
2.161
1.00
16.43


262
CB
GLU
A
35
11.855
28.761
1.577
1.00
15.39


263
CG
GLU
A
35
12.379
29.019
0.228
1.00
17.59


264
CD
GLU
A
35
12.187
30.512
−0.087
1.00
14.10


265
OE1
GLU
A
35
13.022
31.331
0.398
1.00
15.22


266
OE2
GLU
A
35
11.194
30.810
−0.784
1.00
20.61


267
C
GLU
A
35
11.809
27.425
3.643
1.00
14.00


268
O
GLU
A
35
12.651
27.666
4.506
1.00
15.78


269
N
ILE
A
36
10.530
27.183
3.892
1.00
16.23


270
CA
ILE
A
36
10.039
27.185
5.292
1.00
14.47


271
CB
ILE
A
36
8.510
27.040
5.308
1.00
13.60


272
CG2
ILE
A
36
8.015
26.724
6.711
1.00
17.28


273
CG1
ILE
A
36
7.914
28.343
4.763
1.00
14.47


274
CD1
ILE
A
36
6.428
28.274
4.541
1.00
16.94


275
C
ILE
A
36
10.697
26.062
6.097
1.00
14.19


276
O
ILE
A
36
11.255
26.303
7.205
1.00
14.89


277
N
ALA
A
37
10.720
24.884
5.482
1.00
15.18


278
CA
ALA
A
37
11.319
23.723
6.148
1.00
15.59


279
CB
ALA
A
37
11.141
22.502
5.257
1.00
17.71


280
C
ALA
A
37
12.784
23.958
6.483
1.00
16.91


281
O
ALA
A
37
13.254
23.610
7.593
1.00
17.94


282
N
GLU
A
38
13.554
24.566
5.561
1.00
15.64


283
CA
GLU
A
38
14.947
24.850
5.847
1.00
17.27


284
CB
GLU
A
38
15.703
25.267
4.559
1.00
18.26


285
CG
GLU
A
38
15.871
24.166
3.536
1.00
26.66


286
CD
GLU
A
38
16.713
22.998
4.047
1.00
25.35


287
OE1
GLU
A
38
17.656
23.241
4.833
1.00
27.87


288
OE2
GLU
A
38
16.423
21.861
3.643
1.00
30.64


289
C
GLU
A
38
15.189
25.874
6.927
1.00
18.13


290
O
GLU
A
38
16.162
25.771
7.657
1.00
17.88


291
N
ILE
A
39
14.322
26.893
7.055
1.00
16.32


292
CA
ILE
A
39
14.469
27.862
8.132
1.00
16.76


293
CB A
ILE
A
39
13.596
29.114
7.940
0.50
17.98


294
CB B
ILE
A
39
13.552
29.099
7.926
0.50
20.20


295
CG2A
ILE
A
39
13.419
29.872
9.275
0.50
15.47


296
CG2B
ILE
A
39
13.701
30.070
9.112
0.50
20.19


297
CG1A
ILE
A
39
14.290
30.034
6.960
0.50
16.30


298
CG1B
ILE
A
39
13.891
29.783
6.599
0.50
21.26


299
CD1A
ILE
A
39
13.373
31.005
6.323
0.50
12.77


300
CD1B
ILE
A
39
15.255
30.429
6.550
0.50
23.48


301
C
ILE
A
39
14.101
27.176
9.485
1.00
14.27


302
O
ILE
A
39
14.752
27.410
10.487
1.00
17.34


303
N
LEU
A
40
13.111
26.294
9.466
1.00
15.11


304
CA
LEU
A
40
12.778
25.591
10.700
1.00
12.68


305
CB
LEU
A
40
11.566
24.659
10.517
1.00
12.13


306
CG
LEU
A
40
10.254
25.407
10.228
1.00
12.48


307
CD1
LEU
A
40
9.122
24.392
10.022
1.00
16.06


308
CD2
LEU
A
40
9.898
26.311
11.408
1.00
17.03


309
C
LEU
A
40
13.992
24.819
11.146
1.00
15.02


310
O
LEU
A
40
14.265
24.730
12.317
1.00
14.50


311
N
LYS
A
41
14.716
24.243
10.183
1.00
13.32


312
CA
LYS
A
41
15.908
23.470
10.524
1.00
14.52


313
CB
LYS
A
41
16.373
22.651
9.311
1.00
15.64


314
CG
LYS
A
41
17.618
21.819
9.539
1.00
18.37


315
CD
LYS
A
41
18.012
21.109
8.268
1.00
25.04


316
CE
LYS
A
41
19.355
20.435
8.470
1.00
28.16


317
NZ
LYS
A
41
19.776
19.797
7.183
1.00
24.42


318
C
LYS
A
41
17.038
24.386
10.993
1.00
17.40


319
O
LYS
A
41
17.623
24.180
12.049
1.00
21.49


320
N
SER
A
42
17.337
25.429
10.213
1.00
17.40


321
CA
SER
A
42
18.457
26.259
10.617
1.00
19.84


322
CB
SER
A
42
18.821
27.258
9.504
1.00
22.89


323
OG
SER
A
42
17.798
28.213
9.318
1.00
26.40


324
C
SER
A
42
18.209
26.949
11.933
1.00
21.31


325
O
SER
A
42
19.154
27.210
12.680
1.00
22.43


326
N
GLU
A
43
16.936
27.199
12.261
1.00
19.93


327
CA
GLU
A
43
16.581
27.857
13.509
1.00
17.11


328
CB
GLU
A
43
15.289
28.678
13.335
1.00
20.03


329
CG
GLU
A
43
15.506
29.879
12.424
1.00
20.26


330
CD
GLU
A
43
16.464
30.905
13.044
1.00
21.79


331
OE1
GLU
A
43
16.183
31.346
14.183
1.00
24.68


332
OE2
GLU
A
43
17.460
31.260
12.356
1.00
24.12


333
C
GLU
A
43
16.454
26.907
14.685
1.00
19.29


334
O
GLU
A
43
16.111
27.309
15.804
1.00
21.07


335
N
GLY
A
44
16.708
25.625
14.410
1.00
18.95


336
CA
GLY
A
44
16.684
24.647
15.485
1.00
18.08


337
C
GLY
A
44
15.331
24.095
15.866
1.00
20.18


338
O
GLY
A
44
15.224
23.368
16.853
1.00
22.41


339
N
PHE
A
45
14.292
24.392
15.090
1.00
16.56


340
CA
PHE
A
45
12.976
23.887
15.466
1.00
16.87


341
CB
PHE
A
45
11.905
24.822
14.943
1.00
12.09


342
CG
PHE
A
45
11.759
26.075
15.751
1.00
13.00


343
CD1
PHE
A
45
11.169
26.036
17.004
1.00
12.05


344
CD2
PHE
A
45
12.218
27.292
15.266
1.00
14.04


345
CE1
PHE
A
45
11.036
27.199
17.769
1.00
14.85


346
CE2
PHE
A
45
12.090
28.457
16.027
1.00
15.80


347
CZ
PHE
A
45
11.495
28.398
17.271
1.00
13.65


348
C
PHE
A
45
12.704
22.468
15.003
1.00
18.86


349
O
PHE
A
45
11.857
21.797
15.567
1.00
17.57


350
N
ILE
A
46
13.335
22.059
13.899
1.00
16.30


351
CA
ILE
A
46
13.224
20.683
13.456
1.00
17.57


352
CB
ILE
A
46
12.405
20.489
12.157
1.00
13.61


353
CG2
ILE
A
46
10.982
20.969
12.347
1.00
14.82


354
CG1
ILE
A
46
13.105
21.175
10.985
1.00
16.03


355
CD1
ILE
A
46
12.437
20.868
9.686
1.00
17.25


356
C
ILE
A
46
14.633
20.155
13.262
1.00
16.90


357
O
ILE
A
46
15.608
20.926
13.169
1.00
17.77


358
N
LYS
A
47
14.754
18.840
13.175
1.00
17.55


359
CA
LYS
A
47
16.050
18.200
13.042
1.00
20.67


360
CB
LYS
A
47
15.916
16.801
13.653
1.00
22.04


361
CG
LYS
A
47
17.167
15.986
13.857
1.00
34.96


362
CD
LYS
A
47
16.813
14.776
14.737
1.00
40.91


363
CE
LYS
A
47
18.049
14.001
15.192
1.00
45.35


364
NZ
LYS
A
47
17.689
12.841
16.081
1.00
47.44


365
C
LYS
A
47
16.587
18.137
11.627
1.00
23.96


366
O
LYS
A
47
17.791
18.352
11.410
1.00
27.25


367
N
ASN
A
48
15.724
17.862
10.660
1.00
23.14


368
CA
ASN
A
48
16.204
17.780
9.277
1.00
23.76


369
CB
ASN
A
48
17.093
16.533
9.136
1.00
28.30


370
CG
ASN
A
48
17.725
16.427
7.773
1.00
33.93


371
OD1
ASN
A
48
18.184
17.433
7.219
1.00
35.73


372
ND2
ASN
A
48
17.758
15.209
7.223
1.00
36.71


373
C
ASN
A
48
15.055
17.742
8.283
1.00
25.78


374
O
ASN
A
48
13.897
17.606
8.684
1.00
18.82


375
N
VAL
A
49
15.387
17.875
6.990
1.00
20.75


376
CA
VAL
A
49
14.418
17.827
5.891
1.00
20.69


377
CB
VAL
A
49
14.117
19.222
5.268
1.00
22.40


378
CG1
VAL
A
49
12.892
19.144
4.264
1.00
21.21


379
CG2
VAL
A
49
13.924
20.230
6.368
1.00
24.41


380
C
VAL
A
49
15.049
17.019
4.783
1.00
21.17


381
O
VAL
A
49
16.189
17.291
4.415
1.00
28.56


382
N
GLU
A
50
14.309
16.058
4.262
1.00
20.50


383
CA
GLU
A
50
14.783
15.246
3.130
1.00
22.14


384
CB
GLU
A
50
14.761
13.754
3.486
1.00
24.09


385
CG
GLU
A
50
15.952
13.292
4.274
1.00
29.46


386
CD
GLU
A
50
15.883
11.830
4.657
1.00
31.31


387
OE1
GLU
A
50
16.876
11.335
5.234
1.00
38.72


388
OE2
GLU
A
50
14.838
11.187
4.405
1.00
31.03


389
C
GLU
A
50
13.787
15.497
1.994
1.00
23.91


390
O
GLU
A
50
12.589
15.669
2.233
1.00
20.50


391
N
TYR
A
51
14.281
15.482
0.747
1.00
26.16


392
CA
TYR
A
51
13.432
15.676
−0.432
1.00
22.90


393
CB
TYR
A
51
14.198
16.524
−1.454
1.00
24.90


394
CG
TYR
A
51
14.616
17.903
−0.958
1.00
29.44


395
CD1
TYR
A
51
15.629
18.620
−1.617
1.00
33.16


396
CE1
TYR
A
51
16.051
19.883
−1.158
1.00
31.21


397
CD2
TYR
A
51
14.020
18.489
0.172
1.00
32.63


398
CE2
TYR
A
51
14.432
19.746
0.648
1.00
29.86


399
CZ
TYR
A
51
15.453
20.435
−0.022
1.00
37.58


400
OH
TYR
A
51
15.918
21.647
0.458
1.00
39.41


401
C
TYR
A
51
13.136
14.263
−0.982
1.00
21.94


402
O
TYR
A
51
14.049
13.483
−1.173
1.00
27.59


403
N
VAL
A
52
11.861
13.956
−1.220
1.00
21.78


404
CA
VAL
A
52
11.417
12.645
−1.653
1.00
26.05


405
CB
VAL
A
52
10.458
12.039
−0.556
1.00
25.02


406
CG1
VAL
A
52
9.963
10.670
−0.928
1.00
28.46


407
CG2
VAL
A
52
11.171
11.989
0.781
1.00
29.62


408
C
VAL
A
52
10.667
12.687
−2.982
1.00
22.77


409
O
VAL
A
52
9.787
13.492
−3.177
1.00
21.42


410
N
GLU
A
53
11.002
11.783
−3.900
1.00
25.82


411
CA
GLU
A
53
10.315
11.722
−5.182
1.00
24.93


412
CB
GLU
A
53
11.183
10.936
−6.170
1.00
31.27


413
CG
GLU
A
53
12.599
11.449
−6.262
1.00
35.20


414
CD
GLU
A
53
13.443
10.666
−7.242
0.50
39.45


415
OE1
GLU
A
53
12.862
10.086
−8.184
0.50
39.39


416
OE2
GLU
A
53
14.684
10.644
−7.077
0.50
38.84


417
C
GLU
A
53
8.943
11.061
−5.081
1.00
26.25


418
O
GLU
A
53
8.701
10.201
−4.212
1.00
27.80


419
N
ASP
A
54
8.029
11.480
−5.945
1.00
22.37


420
CA
ASP
A
54
6.694
10.889
−6.004
1.00
28.05


421
CB
ASP
A
54
5.725
11.540
−4.992
1.00
26.65


422
CG
ASP
A
54
5.247
12.911
−5.400
1.00
27.40


423
OD1
ASP
A
54
5.824
13.516
−6.325
1.00
26.17


424
OD2
ASP
A
54
4.283
13.394
−4.767
1.00
30.42


425
C
ASP
A
54
6.229
11.023
−7.467
1.00
26.89


426
O
ASP
A
54
7.054
11.330
−8.329
1.00
27.63


427
N
ASP
A
55
4.948
10.786
−7.750
1.00
32.96


428
CA
ASP
A
55
4.440
10.860
−9.127
1.00
36.53


429
CB
ASP
A
55
3.444
9.715
−9.347
1.00
39.57


430
CG
ASP
A
55
2.172
9.876
−8.515
1.00
45.50


431
OD1
ASP
A
55
2.252
10.429
−7.401
1.00
47.07


432
OD2
ASP
A
55
1.093
9.450
−8.972
1.00
48.67


433
C
ASP
A
55
3.786
12.216
−9.453
1.00
38.03


434
O
ASP
A
55
2.973
12.349
−10.395
1.00
39.71


435
N
LYS
A
56
4.152
13.226
−8.671
1.00
33.03


436
CA
LYS
A
56
3.630
14.574
−8.827
1.00
31.69


437
CB
LYS
A
56
2.611
14.862
−7.713
1.00
33.79


438
CG
LYS
A
56
1.376
13.938
−7.780
1.00
39.31


439
CD
LYS
A
56
0.462
14.111
−6.564
1.00
41.42


440
CE
LYS
A
56
−0.552
12.982
−6.461
0.50
44.11


441
NZ
LYS
A
56
−1.562
13.216
−5.374
0.50
44.17


442
C
LYS
A
56
4.811
15.532
−8.745
1.00
32.28


443
O
LYS
A
56
5.744
15.446
−9.556
1.00
32.47


444
N
GLN
A
57
4.822
16.426
−7.761
1.00
26.84


445
CA
GLN
A
57
5.947
17.356
−7.690
1.00
25.59


446
CB
GLN
A
57
5.455
18.807
−7.854
1.00
28.56


447
CG
GLN
A
57
4.630
19.349
−6.716
1.00
33.11


448
CD
GLN
A
57
4.089
20.762
−7.032
1.00
41.66


449
OE1
GLN
A
57
3.819
21.563
−6.126
1.00
40.37


450
NE2
GLN
A
57
3.933
21.063
−8.327
1.00
39.88


451
C
GLN
A
57
6.869
17.228
−6.458
1.00
22.95


452
O
GLN
A
57
7.460
18.204
−6.003
1.00
24.47


453
N
GLY
A
58
7.000
16.002
−5.954
1.00
22.17


454
CA
GLY
A
58
7.871
15.743
−4.843
1.00
18.50


455
C
GLY
A
58
7.246
15.913
−3.473
1.00
19.05


456
O
GLY
A
58
6.213
16.547
−3.300
1.00
18.74


457
N
VAL
A
59
7.932
15.306
−2.522
1.00
19.84


458
CA
VAL
A
59
7.518
15.281
−1.122
1.00
21.94


459
CB
VAL
A
59
7.141
13.809
−0.757
1.00
19.26


460
CG1
VAL
A
59
7.325
13.542
0.762
1.00
24.81


461
CG2
VAL
A
59
5.699
13.552
−1.174
1.00
23.20


462
C
VAL
A
59
8.615
15.811
−0.202
1.00
17.61


463
O
VAL
A
59
9.806
15.744
−0.494
1.00
18.55


464
N
LEU
A
60
8.214
16.469
0.894
1.00
17.50


465
CA
LEU
A
60
9.187
16.927
1.890
1.00
16.68


466
CB
LEU
A
60
8.917
18.375
2.301
1.00
20.18


467
CG
LEU
A
60
8.949
19.386
1.164
1.00
19.12


468
CD1
LEU
A
60
8.627
20.755
1.751
1.00
21.10


469
CD2
LEU
A
60
10.335
19.432
0.535
1.00
22.00


470
C
LEU
A
60
9.027
16.068
3.147
1.00
14.21


471
O
LEU
A
60
7.901
15.894
3.633
1.00
19.41


472
N
ARG
A
61
10.128
15.508
3.620
1.00
16.80


473
CA
ARG
A
61
10.062
14.670
4.820
1.00
14.82


474
CB
ARG
A
61
10.752
13.321
4.554
1.00
19.03


475
CG
ARG
A
61
10.862
12.440
5.794
1.00
20.10


476
CD
ARG
A
61
11.600
11.148
5.423
1.00
21.67


477
NE
ARG
A
61
10.792
10.381
4.498
1.00
25.73


478
CZ
ARG
A
61
11.312
9.660
3.515
1.00
24.65


479
NH1
ARG
A
61
12.623
9.638
3.365
1.00
26.59


480
NH2
ARG
A
61
10.517
8.958
2.713
1.00
23.07


481
C
ARG
A
61
10.764
15.456
5.909
1.00
15.91


482
O
ARG
A
61
11.903
15.814
5.788
1.00
19.77


483
N
LEU
A
62
9.995
15.842
6.924
1.00
15.80


484
CA
LEU
A
62
10.540
16.626
8.032
1.00
15.07


485
CB
LEU
A
62
9.526
17.710
8.412
1.00
14.09


486
CG A
LEU
A
62
9.612
19.002
7.538
0.50
11.86


487
CG B
LEU
A
62
9.092
18.710
7.313
0.50
19.47


488
CD1A
LEU
A
62
9.154
18.712
6.107
0.50
14.08


489
CD1B
LEU
A
62
8.156
19.737
7.881
0.50
15.45


490
CD2A
LEU
A
62
8.756
20.118
8.133
0.50
10.22


491
CD2B
LEU
A
62
10.308
19.396
6.747
0.50
22.00


492
C
LEU
A
62
10.755
15.708
9.237
1.00
13.03


493
O
LEU
A
62
9.854
14.957
9.588
1.00
19.09


494
N
PHE
A
63
11.912
15.853
9.852
1.00
15.26


495
CA
PHE
A
63
12.268
15.085
11.061
1.00
13.36


496
CB
PHE
A
63
13.692
14.580
10.949
1.00
17.23


497
CG
PHE
A
63
13.838
13.490
9.935
1.00
26.02


498
CD1
PHE
A
63
13.993
13.809
8.587
1.00
24.64


499
CD2
PHE
A
63
13.772
12.146
10.322
1.00
25.41


500
CE1
PHE
A
63
14.086
12.806
7.606
1.00
34.29


501
CE2
PHE
A
63
13.864
11.125
9.347
1.00
30.88


502
CZ
PHE
A
63
14.020
11.458
7.992
1.00
31.24


503
C
PHE
A
63
12.129
16.041
12.232
1.00
16.16


504
O
PHE
A
63
12.857
17.025
12.336
1.00
16.35


505
N
LEU
A
64
11.188
15.721
13.124
1.00
12.15


506
CA
LEU
A
64
10.949
16.628
14.265
1.00
13.95


507
CB
LEU
A
64
9.560
16.375
14.800
1.00
16.05


508
CG
LEU
A
64
8.443
16.513
13.753
1.00
15.55


509
CD1
LEU
A
64
7.115
16.434
14.462
1.00
14.33


510
CD2
LEU
A
64
8.494
17.868
12.999
1.00
18.42


511
C
LEU
A
64
11.995
16.495
15.341
1.00
16.79


512
O
LEU
A
64
12.764
15.541
15.331
1.00
16.10


513
N
LYS
A
65
12.018
17.455
16.268
1.00
14.93


514
CA
LYS
A
65
13.088
17.498
17.273
1.00
16.15


515
CB
LYS
A
65
13.953
18.742
17.031
1.00
16.36


516
CG
LYS
A
65
15.259
18.779
17.846
1.00
21.68


517
CD
LYS
A
65
16.138
19.944
17.424
1.00
24.61


518
CE
LYS
A
65
17.404
20.003
18.254
1.00
33.12


519
NZ
LYS
A
65
18.140
21.237
17.860
1.00
43.56


520
C
LYS
A
65
12.514
17.552
18.671
1.00
13.82


521
O
LYS
A
65
11.563
18.310
18.941
1.00
13.61


522
N
TYR
A
66
13.072
16.708
19.526
1.00
14.18


523
CA
TYR
A
66
12.679
16.640
20.929
1.00
14.37


524
CB
TYR
A
66
12.023
15.288
21.224
1.00
12.63


525
CG
TYR
A
66
10.835
15.085
20.291
1.00
13.29


526
CD1
TYR
A
66
9.609
15.707
20.538
1.00
13.69


527
CE1
TYR
A
66
8.549
15.590
19.660
1.00
10.82


528
CD2
TYR
A
66
10.952
14.337
19.115
1.00
12.56


529
CE2
TYR
A
66
9.886
14.225
18.218
1.00
14.32


530
CZ
TYR
A
66
8.683
14.849
18.492
1.00
10.23


531
OH
TYR
A
66
7.638
14.780
17.596
1.00
14.03


532
C
TYR
A
66
13.934
16.887
21.716
1.00
17.42


533
O
TYR
A
66
15.024
16.485
21.323
1.00
18.85


534
N
GLY
A
67
13.767
17.579
22.832
1.00
14.07


535
CA
GLY
A
67
14.908
17.936
23.635
1.00
16.44


536
C
GLY
A
67
15.520
16.825
24.458
1.00
12.83


537
O
GLY
A
67
15.195
15.612
24.419
1.00
14.24


538
N
GLN
A
68
16.444
17.296
25.294
1.00
19.98


539
CA
GLN
A
68
17.198
16.425
26.143
1.00
18.84


540
CB
GLN
A
68
18.177
17.301
26.948
1.00
23.70


541
CG
GLN
A
68
19.007
18.305
26.074
1.00
24.68


542
CD
GLN
A
68
19.915
17.585
25.083
1.00
30.35


543
OE1
GLN
A
68
20.240
18.098
24.001
1.00
32.02


544
NE2
GLN
A
68
20.316
16.394
25.446
1.00
25.11


545
C
GLN
A
68
16.310
15.597
27.098
1.00
19.88


546
O
GLN
A
68
16.651
14.507
27.503
1.00
20.76


547
N
ASN
A
69
15.154
16.139
27.467
1.00
14.22


548
CA
ASN
A
69
14.203
15.412
28.340
1.00
12.44


549
CB
ASN
A
69
13.869
16.247
29.555
1.00
10.77


550
CG
ASN
A
69
15.064
16.407
30.431
1.00
10.57


551
OD1
ASN
A
69
15.457
15.425
31.071
1.00
14.00


552
ND2
ASN
A
69
15.697
17.569
30.412
1.00
12.98


553
C
ASN
A
69
12.912
15.129
27.570
1.00
12.79


554
O
ASN
A
69
11.825
14.974
28.173
1.00
14.19


555
N
ASP
A
70
13.100
14.917
26.276
1.00
11.79


556
CA
ASP
A
70
12.025
14.595
25.313
1.00
12.02


557
CB
ASP
A
70
11.389
13.228
25.621
1.00
17.75


558
CG
ASP
A
70
12.406
12.087
25.591
1.00
19.88


559
OD1
ASP
A
70
12.497
11.343
26.604
1.00
23.44


560
OD2
ASP
A
70
13.099
11.949
24.563
1.00
21.00


561
C
ASP
A
70
10.937
15.657
25.224
1.00
13.39


562
O
ASP
A
70
9.861
15.382
24.666
1.00
13.36


563
N
GLU
A
71
11.201
16.863
25.704
1.00
10.62


564
CA
GLU
A
71
10.242
17.938
25.548
1.00
10.37


565
CB
GLU
A
71
10.604
19.104
26.511
1.00
14.47


566
CG
GLU
A
71
11.821
19.909
26.133
1.00
14.73


567
CD
GLU
A
71
13.156
19.327
26.526
1.00
14.61


568
OE1
GLU
A
71
13.331
18.126
26.789
1.00
12.82


569
OE2
GLU
A
71
14.102
20.160
26.520
1.00
27.36


570
C
GLU
A
71
10.200
18.408
24.092
1.00
12.85


571
O
GLU
A
71
11.197
18.298
23.355
1.00
13.50


572
N
ARG
A
72
9.047
18.872
23.638
1.00
13.46


573
CA
ARG
A
72
8.959
19.300
22.236
1.00
12.06


574
CB
ARG
A
72
7.489
19.429
21.832
1.00
14.51


575
CG
ARG
A
72
6.665
18.136
22.031
1.00
13.23


576
CD
ARG
A
72
5.223
18.386
21.673
1.00
13.43


577
NE
ARG
A
72
4.374
17.226
21.926
1.00
11.18


578
CZ
ARG
A
72
3.848
16.887
23.092
1.00
11.42


579
NH1
ARG
A
72
4.113
17.649
24.169
1.00
13.06


580
NH2
ARG
A
72
3.021
15.824
23.182
1.00
13.37


581
C
ARG
A
72
9.660
20.615
22.011
1.00
11.47


582
O
ARG
A
72
9.361
21.575
22.711
1.00
13.15


583
N
VAL
A
73
10.534
20.664
21.008
1.00
13.86


584
CA
VAL
A
73
11.256
21.876
20.721
1.00
14.77


585
CB
VAL
A
73
12.448
21.548
19.821
1.00
15.31


586
CG1
VAL
A
73
13.058
22.833
19.241
1.00
20.54


587
CG2
VAL
A
73
13.489
20.762
20.643
1.00
15.55


588
C
VAL
A
73
10.272
22.904
20.153
1.00
16.77


589
O
VAL
A
73
10.422
24.086
20.381
1.00
15.01


590
N
ILE
A
74
9.272
22.452
19.389
1.00
14.14


591
CA
ILE
A
74
8.235
23.348
18.905
1.00
12.14


592
CB
ILE
A
74
7.677
22.887
17.529
1.00
11.54


593
CG2
ILE
A
74
6.406
23.691
17.186
1.00
12.82


594
CG1
ILE
A
74
8.753
23.086
16.462
1.00
13.81


595
CD1
ILE
A
74
8.334
22.451
15.075
1.00
12.99


596
C
ILE
A
74
7.066
23.344
19.903
1.00
13.54


597
O
ILE
A
74
6.579
22.289
20.291
1.00
15.74


598
N
THR
A
75
6.680
24.514
20.382
1.00
12.14


599
CA
THR
A
75
5.510
24.628
21.230
1.00
13.84


600
CB
THR
A
75
5.731
25.709
22.300
1.00
12.46


601
OG1
THR
A
75
6.743
25.218
23.179
1.00
15.45


602
CG2
THR
A
75
4.478
25.976
23.111
1.00
18.14


603
C
THR
A
75
4.297
24.916
20.337
1.00
14.98


604
O
THR
A
75
3.187
24.353
20.522
1.00
17.04


605
N
GLY
A
76
4.463
25.826
19.375
1.00
11.66


606
CA
GLY
A
76
3.343
26.123
18.507
1.00
12.65


607
C
GLY
A
76
3.684
26.762
17.177
1.00
12.76


608
O
GLY
A
76
4.806
27.221
16.964
1.00
13.34


609
N
LEU
A
77
2.713
26.755
16.279
1.00
12.96


610
CA
LEU
A
77
2.888
27.371
14.964
1.00
12.42


611
CB
LEU
A
77
3.072
26.322
13.842
1.00
14.28


612
CG
LEU
A
77
4.132
25.265
14.107
1.00
12.84


613
CD1
LEU
A
77
3.401
24.050
14.640
1.00
17.27


614
CD2
LEU
A
77
4.956
24.885
12.857
1.00
15.61


615
C
LEU
A
77
1.582
28.080
14.667
1.00
14.97


616
O
LEU
A
77
0.487
27.554
14.965
1.00
18.39


617
N
LYS
A
78
1.655
29.236
14.041
1.00
10.89


618
CA
LYS
A
78
0.416
29.955
13.757
1.00
10.92


619
CB
LYS
A
78
0.172
31.055
14.804
1.00
12.46


620
CG
LYS
A
78
−1.154
31.763
14.642
1.00
15.96


621
CD
LYS
A
78
−1.350
32.790
15.742
1.00
22.89


622
CE
LYS
A
78
−2.622
33.607
15.540
1.00
29.30


623
NZ
LYS
A
78
−2.558
34.367
14.253
1.00
38.34


624
C
LYS
A
78
0.513
30.619
12.386
1.00
12.82


625
O
LYS
A
78
1.510
31.253
12.080
1.00
12.93


626
N
ARG
A
79
−0.475
30.382
11.519
1.00
11.89


627
CA
ARG
A
79
−0.494
31.037
10.220
1.00
10.36


628
CB
ARG
A
79
−1.506
30.340
9.317
1.00
11.45


629
CG
ARG
A
79
−1.630
30.922
7.924
1.00
10.70


630
CD
ARG
A
79
−0.428
30.458
7.065
1.00
11.44


631
NE
ARG
A
79
−0.709
30.696
5.643
1.00
10.29


632
CZ
ARG
A
79
−0.041
31.473
4.800
1.00
11.86


633
NH1
ARG
A
79
1.003
32.198
5.180
1.00
10.82


634
NH2
ARG
A
79
−0.424
31.510
3.506
1.00
13.18


635
C
ARG
A
79
−0.898
32.485
10.467
1.00
10.70


636
O
ARG
A
79
−1.844
32.761
11.213
1.00
12.98


637
N
ILE
A
80
−0.207
33.439
9.816
1.00
9.68


638
CA
ILE
A
80
−0.498
34.872
10.004
1.00
11.10


639
CB
ILE
A
80
0.816
35.639
10.398
1.00
10.52


640
CG2
ILE
A
80
0.556
37.170
10.588
1.00
10.50


641
CG1
ILE
A
80
1.316
35.053
11.733
1.00
11.58


642
CD1
ILE
A
80
0.359
35.297
12.974
1.00
15.29


643
C
ILE
A
80
−1.136
35.413
8.772
1.00
12.17


644
O
ILE
A
80
−2.353
35.571
8.728
1.00
11.92


645
N
SER
A
81
−0.344
35.677
7.729
1.00
10.37


646
CA
SER
A
81
−0.904
36.120
6.481
1.00
8.76


647
CB
SER
A
81
0.254
36.562
5.536
1.00
8.86


648
OG
SER
A
81
−0.277
37.045
4.338
1.00
12.21


649
C
SER
A
81
−1.681
34.906
5.922
1.00
10.94


650
O
SER
A
81
−1.324
33.758
6.143
1.00
11.56


651
N
LYS
A
82
−2.727
35.198
5.145
1.00
11.16


652
CA
LYS
A
82
−3.548
34.134
4.538
1.00
12.55


653
CB
LYS
A
82
−4.784
33.856
5.398
1.00
14.71


654
CG
LYS
A
82
−4.396
33.348
6.774
1.00
12.80


655
CD
LYS
A
82
−5.621
33.057
7.701
1.00
18.06


656
CE
LYS
A
82
−5.073
32.703
9.096
1.00
21.61


657
NZ
LYS
A
82
−6.120
32.420
10.082
1.00
32.93


658
C
LYS
A
82
−3.989
34.584
3.184
1.00
12.61


659
O
LYS
A
82
−3.998
35.755
2.894
1.00
13.82


660
N
PRO
A
83
−4.357
33.629
2.302
1.00
14.58


661
CD
PRO
A
83
−4.305
32.155
2.405
1.00
17.91


662
CA
PRO
A
83
−4.794
34.083
0.974
1.00
14.56


663
CB
PRO
A
83
−5.088
32.760
0.231
1.00
15.53


664
CG
PRO
A
83
−4.146
31.756
0.948
1.00
16.19


665
C
PRO
A
83
−6.014
34.979
1.077
1.00
14.00


666
O
PRO
A
83
−6.964
34.658
1.776
1.00
16.77


667
N
GLY
A
84
−5.918
36.115
0.383
1.00
15.18


668
CA
GLY
A
84
−6.980
37.103
0.402
1.00
15.76


669
C
GLY
A
84
−7.022
37.943
1.657
1.00
15.78


670
O
GLY
A
84
−7.873
38.827
1.783
1.00
16.65


671
N
LEU
A
85
−6.110
37.681
2.602
1.00
14.27


672
CA
LEU
A
85
−6.075
38.416
3.879
1.00
12.30


673
CB
LEU
A
85
−6.739
37.573
4.960
1.00
13.25


674
CG
LEU
A
85
−8.234
37.251
4.729
1.00
13.75


675
CD1
LEU
A
85
−8.639
36.120
5.626
1.00
15.04


676
CD2
LEU
A
85
−9.052
38.489
5.038
1.00
18.34


677
C
LEU
A
85
−4.570
38.552
4.204
1.00
11.17


678
O
LEU
A
85
−4.102
38.096
5.231
1.00
12.96


679
N
ARG
A
86
−3.890
39.225
3.306
1.00
13.55


680
CA
ARG
A
86
−2.425
39.357
3.426
1.00
11.95


681
CB
ARG
A
86
−1.859
39.999
2.156
1.00
14.49


682
CG
ARG
A
86
−0.344
40.227
2.136
1.00
17.98


683
CD
ARG
A
86
0.236
40.268
0.644
1.00
17.43


684
NE
ARG
A
86
1.670
40.580
0.600
1.00
18.04


685
CZ
ARG
A
86
2.156
41.811
0.538
1.00
21.23


686
NH1
ARG
A
86
1.322
42.858
0.504
1.00
22.22


687
NH2
ARG
A
86
3.468
42.009
0.510
1.00
18.96


688
C
ARG
A
86
−2.042
40.197
4.606
1.00
13.56


689
O
ARG
A
86
−2.766
41.169
4.971
1.00
14.01


690
N
VAL
A
87
−0.926
39.783
5.238
1.00
9.25


691
CA
VAL
A
87
−0.338
40.559
6.339
1.00
9.09


692
CB
VAL
A
87
−0.229
39.735
7.584
1.00
8.47


693
CG1
VAL
A
87
0.553
40.487
8.676
1.00
12.12


694
CG2
VAL
A
87
−1.661
39.516
8.105
1.00
11.24


695
C
VAL
A
87
1.077
40.956
5.919
1.00
10.79


696
O
VAL
A
87
1.913
40.081
5.739
1.00
10.09


697
N
TYR
A
88
1.297
42.255
5.750
1.00
15.79


698
CA
TYR
A
88
2.605
42.825
5.405
1.00
15.47


699
CB
TYR
A
88
2.498
43.608
4.112
1.00
12.62


700
CG
TYR
A
88
3.703
44.530
3.834
1.00
17.48


701
CD1
TYR
A
88
4.906
44.009
3.309
1.00
14.80


702
CE1
TYR
A
88
6.012
44.852
3.105
1.00
18.42


703
CD2
TYR
A
88
3.642
45.892
4.144
1.00
20.80


704
CE2
TYR
A
88
4.735
46.720
3.944
1.00
20.23


705
CZ
TYR
A
88
5.907
46.198
3.427
1.00
20.55


706
OH
TYR
A
88
6.987
47.068
3.190
1.00
24.23


707
C
TYR
A
88
3.057
43.742
6.518
1.00
16.01


708
O
TYR
A
88
2.284
44.560
7.020
1.00
15.46


709
N
ALA
A
89
4.293
43.540
6.975
1.00
11.50


710
CA
ALA
A
89
4.864
44.395
8.011
1.00
10.38


711
CB
ALA
A
89
5.488
43.586
9.101
1.00
14.07


712
C
ALA
A
89
5.936
45.230
7.349
1.00
16.04


713
O
ALA
A
89
6.851
44.668
6.748
1.00
16.15


714
N
LYS
A
90
5.822
46.562
7.419
1.00
16.05


715
CA
LYS
A
90
6.889
47.351
6.860
1.00
18.86


716
CB
LYS
A
90
6.501
48.834
6.782
1.00
17.60


717
CG
LYS
A
90
6.214
49.437
8.122
1.00
21.58


718
CD
LYS
A
90
6.033
50.969
7.971
1.00
33.81


719
CE
LYS
A
90
4.588
51.376
8.089
1.00
40.08


720
NZ
LYS
A
90
4.469
52.869
8.168
1.00
44.32


721
C
LYS
A
90
8.098
47.144
7.787
1.00
17.54


722
O
LYS
A
90
7.966
46.636
8.904
1.00
16.76


723
N
ALA
A
91
9.278
47.576
7.337
1.00
16.64


724
CA
ALA
A
91
10.479
47.366
8.128
1.00
18.67


725
CB
ALA
A
91
11.655
48.041
7.427
1.00
18.91


726
C
ALA
A
91
10.442
47.765
9.606
1.00
18.05


727
O
ALA
A
91
10.855
47.001
10.488
1.00
17.91


728
N
SER
A
92
9.917
48.942
9.896
1.00
23.72


729
CA
SER
A
92
9.857
49.403
11.285
1.00
23.89


730
CB
SER
A
92
9.585
50.926
11.318
1.00
26.05


731
OG
SER
A
92
8.330
51.249
10.729
1.00
26.98


732
C
SER
A
92
8.804
48.705
12.137
1.00
25.38


733
O
SER
A
92
8.788
48.889
13.352
1.00
27.23


734
N
GLU
A
93
7.916
47.913
11.516
1.00
20.29


735
CA
GLU
A
93
6.842
47.260
12.254
1.00
21.56


736
CB
GLU
A
93
5.502
47.560
11.571
1.00
19.70


737
CG
GLU
A
93
5.106
49.036
11.582
1.00
28.45


738
CD
GLU
A
93
5.101
49.629
12.970
1.00
29.50


739
OE1
GLU
A
93
4.379
49.096
13.837
1.00
26.15


740
OE2
GLU
A
93
5.827
50.621
13.210
1.00
39.50


741
C
GLU
A
93
7.049
45.751
12.307
1.00
17.97


742
O
GLU
A
93
6.153
45.012
12.704
1.00
18.18


743
N
MET
A
94
8.238
45.313
11.919
1.00
18.42


744
CA
MET
A
94
8.559
43.884
11.902
1.00
15.60


745
CB
MET
A
94
10.022
43.738
11.450
1.00
17.32


746
CG
MET
A
94
10.506
42.298
11.261
1.00
14.83


747
SD
MET
A
94
9.488
41.315
10.140
1.00
15.25


748
CE
MET
A
94
9.452
42.297
8.736
1.00
13.31


749
C
MET
A
94
8.303
43.333
13.298
1.00
18.99


750
O
MET
A
94
9.006
43.707
14.242
1.00
21.10


751
N
PRO
A
95
7.276
42.467
13.462
1.00
16.98


752
CD
PRO
A
95
6.432
41.893
12.376
1.00
15.20


753
CA
PRO
A
95
6.904
41.888
14.764
1.00
16.05


754
CB
PRO
A
95
5.548
41.244
14.471
1.00
18.87


755
CG
PRO
A
95
5.759
40.680
13.042
1.00
18.12


756
C
PRO
A
95
7.883
40.914
15.385
1.00
19.74


757
O
PRO
A
95
8.725
40.319
14.679
1.00
18.41


758
N
LYS
A
96
7.829
40.810
16.719
1.00
20.86


759
CA
LYS
A
96
8.642
39.817
17.439
1.00
15.85


760
CB
LYS
A
96
9.493
40.412
18.582
1.00
20.02


761
CG
LYS
A
96
10.828
41.009
18.113
1.00
23.65


762
CD
LYS
A
96
11.659
41.458
19.306
1.00
26.92


763
CE
LYS
A
96
13.005
41.929
18.852
1.00
31.82


764
NZ
LYS
A
96
13.814
42.480
19.977
1.00
38.15


765
C
LYS
A
96
7.640
38.861
18.013
1.00
17.68


766
O
LYS
A
96
6.505
39.237
18.327
1.00
20.06


767
N
VAL
A
97
8.048
37.599
18.089
1.00
15.40


768
CA
VAL
A
97
7.198
36.538
18.615
1.00
13.12


769
CB
VAL
A
97
7.302
35.297
17.676
1.00
14.86


770
CG1
VAL
A
97
6.486
34.125
18.179
1.00
18.80


771
CG2
VAL
A
97
6.754
35.714
16.258
1.00
17.83


772
C
VAL
A
97
7.750
36.254
20.009
1.00
16.78


773
O
VAL
A
97
8.926
35.882
20.157
1.00
16.90


774
N
LEU
A
98
6.873
36.385
21.019
1.00
18.18


775
CA
LEU
A
98
7.280
36.214
22.436
1.00
19.32


776
CB
LEU
A
98
7.452
34.717
22.818
1.00
24.20


777
CG
LEU
A
98
6.204
33.827
22.670
1.00
25.60


778
CD1
LEU
A
98
6.543
32.388
23.109
1.00
22.47


779
CD2
LEU
A
98
5.032
34.418
23.497
1.00
22.24


780
C
LEU
A
98
8.534
37.002
22.768
1.00
22.57


781
O
LEU
A
98
9.491
36.489
23.376
1.00
21.80


782
N
ASN
A
99
8.528
38.265
22.346
1.00
20.95


783
CA
ASN
A
99
9.639
39.167
22.588
1.00
21.68


784
CB
ASN
A
99
9.751
39.444
24.102
1.00
20.16


785
CG
ASN
A
99
8.731
40.461
24.605
1.00
28.35


786
OD1
ASN
A
99
8.645
40.709
25.808
1.00
29.89


787
ND2
ASN
A
99
7.955
41.054
23.699
1.00
22.63


788
C
ASN
A
99
10.985
38.682
22.028
1.00
21.34


789
O
ASN
A
99
12.037
39.161
22.432
1.00
22.61


790
N
GLY
A
100
10.971
37.747
21.066
1.00
16.11


791
CA
GLY
A
100
12.221
37.306
20.487
1.00
18.10


792
C
GLY
A
100
12.486
35.832
20.738
1.00
16.81


793
O
GLY
A
100
13.424
35.276
20.175
1.00
18.53


794
N
LEU
A
101
11.650
35.186
21.553
1.00
18.12


795
CA
LEU
A
101
11.877
33.774
21.866
1.00
17.08


796
CB
LEU
A
101
11.258
33.369
23.223
1.00
16.32


797
CG
LEU
A
101
11.960
33.969
24.458
1.00
19.19


798
CD1
LEU
A
101
11.193
33.475
25.709
1.00
21.03


799
CD2
LEU
A
101
13.398
33.542
24.543
1.00
23.46


800
C
LEU
A
101
11.378
32.857
20.773
1.00
16.32


801
O
LEU
A
101
11.834
31.726
20.668
1.00
16.93


802
N
GLY
A
102
10.406
33.340
19.991
1.00
15.32


803
CA
GLY
A
102
9.966
32.567
18.850
1.00
11.91


804
C
GLY
A
102
10.426
33.317
17.598
1.00
14.50


805
O
GLY
A
102
11.206
34.227
17.686
1.00
14.08


806
N
ILE
A
103
9.992
32.878
16.428
1.00
11.41


807
CA
ILE
A
103
10.360
33.553
15.196
1.00
10.51


808
CB
ILE
A
103
11.344
32.716
14.297
1.00
12.15


809
CG2
ILE
A
103
12.684
32.538
15.031
1.00
15.59


810
CG1
ILE
A
103
10.759
31.343
13.931
1.00
13.72


811
CD1
ILE
A
103
11.704
30.512
13.005
1.00
15.76


812
C
ILE
A
103
9.142
33.780
14.332
1.00
11.21


813
O
ILE
A
103
8.162
33.046
14.406
1.00
13.44


814
N
ALA
A
104
9.206
34.835
13.529
1.00
9.11


815
CA
ALA
A
104
8.196
35.037
12.480
1.00
11.44


816
CB
ALA
A
104
7.731
36.490
12.379
1.00
12.52


817
C
ALA
A
104
8.937
34.660
11.192
1.00
14.21


818
O
ALA
A
104
10.139
34.916
11.030
1.00
12.74


819
N
LEU
A
105
8.229
34.008
10.271
1.00
10.13


820
CA
LEU
A
105
8.820
33.679
8.953
1.00
9.95


821
CB
LEU
A
105
8.331
32.332
8.470
1.00
9.52


822
CG
LEU
A
105
8.710
31.200
9.432
1.00
17.45


823
CD1
LEU
A
105
8.104
29.878
8.932
1.00
19.68


824
CD2
LEU
A
105
10.206
31.078
9.536
1.00
23.41


825
C
LEU
A
105
8.283
34.800
8.034
1.00
9.90


826
O
LEU
A
105
7.099
35.097
7.995
1.00
10.55


827
N
VAL
A
106
9.221
35.455
7.327
1.00
9.62


828
CA
VAL
A
106
8.912
36.651
6.531
1.00
10.35


829
CB
VAL
A
106
9.725
37.845
7.062
1.00
12.20


830
CG1
VAL
A
106
9.395
39.124
6.314
1.00
9.56


831
CG2
VAL
A
106
9.476
37.991
8.604
1.00
12.36


832
C
VAL
A
106
9.251
36.425
5.066
1.00
12.29


833
O
VAL
A
106
10.368
36.045
4.741
1.00
11.23


834
N
SER
A
107
8.272
36.627
4.169
1.00
10.90


835
CA
SER
A
107
8.526
36.443
2.729
1.00
12.19


836
CB
SER
A
107
7.240
36.034
1.994
1.00
14.23


837
OG
SER
A
107
7.570
35.730
0.639
1.00
16.39


838
C
SER
A
107
8.985
37.782
2.187
1.00
10.58


839
O
SER
A
107
8.270
38.789
2.292
1.00
11.06


840
N
THR
A
108
10.204
37.818
1.621
1.00
10.16


841
CA
THR
A
108
10.782
39.049
1.128
1.00
10.99


842
CB
THR
A
108
12.017
39.513
1.947
1.00
10.30


843
OG1
THR
A
108
13.142
38.642
1.616
1.00
11.31


844
CG2
THR
A
108
11.749
39.445
3.451
1.00
11.47


845
C
THR
A
108
11.257
38.891
−0.286
1.00
9.32


846
O
THR
A
108
11.201
37.803
−0.875
1.00
11.44


847
N
SER
A
109
11.750
40.012
−0.856
1.00
10.95


848
CA
SER
A
109
12.223
39.937
−2.247
1.00
12.01


849
CB
SER
A
109
12.499
41.334
−2.759
1.00
13.38


850
OG
SER
A
109
13.522
41.854
−1.944
1.00
19.19


851
C
SER
A
109
13.462
39.058
−2.426
1.00
11.60


852
O
SER
A
109
13.771
38.660
−3.551
1.00
12.69


853
N
GLU
A
110
14.123
38.683
−1.328
1.00
11.99


854
CA
GLU
A
110
15.301
37.802
−1.372
1.00
14.00


855
CB A
GLU
A
110
16.487
38.458
−0.640
0.50
15.92


856
CB B
GLU
A
110
16.447
38.405
−0.513
0.50
13.21


857
CG A
GLU
A
110
17.317
39.438
−1.538
0.50
20.73


858
CG B
GLU
A
110
16.924
39.808
−0.907
0.50
12.55


859
CD A
GLU
A
110
18.087
38.755
−2.692
0.50
20.98


860
CD B
GLU
A
110
18.264
40.237
−0.267
0.50
16.47


861
OE1A
GLU
A
110
17.423
38.218
−3.630
0.50
14.75


862
OE1B
GLU
A
110
19.328
39.694
−0.639
0.50
20.77


863
OE2A
GLU
A
110
19.368
38.735
−2.674
0.50
20.13


864
OE2B
GLU
A
110
18.247
41.142
0.605
0.50
21.01


865
C
GLU
A
110
14.998
36.391
−0.844
1.00
15.80


866
O
GLU
A
110
15.924
35.574
−0.683
1.00
17.76


867
N
GLY
A
111
13.708
36.067
−0.653
1.00
11.83


868
CA
GLY
A
111
13.328
34.772
−0.100
1.00
13.35


869
C
GLY
A
111
12.771
34.903
1.322
1.00
10.68


870
O
GLY
A
111
12.666
36.014
1.881
1.00
11.13


871
N
VAL
A
112
12.470
33.747
1.924
1.00
10.43


872
CA
VAL
A
112
11.939
33.694
3.282
1.00
11.99


873
CB
VAL
A
112
11.179
32.365
3.517
1.00
11.37


874
CG1
VAL
A
112
10.583
32.363
4.913
1.00
14.43


875
CG2
VAL
A
112
10.018
32.256
2.519
1.00
11.74


876
C
VAL
A
112
13.097
33.793
4.283
1.00
10.65


877
O
VAL
A
112
14.121
33.141
4.102
1.00
14.31


878
N
ILE
A
113
12.919
34.676
5.252
1.00
11.14


879
CA
ILE
A
113
13.885
34.942
6.300
1.00
12.82


880
CB
ILE
A
113
14.714
36.232
6.040
1.00
12.46


881
CG2
ILE
A
113
15.514
36.051
4.737
1.00
14.34


882
CG1
ILE
A
113
13.839
37.499
6.046
1.00
13.84


883
CD1
ILE
A
113
14.689
38.841
5.855
1.00
12.60


884
C
ILE
A
113
13.172
35.080
7.629
1.00
12.25


885
O
ILE
A
113
11.940
35.138
7.670
1.00
12.19


886
N
THR
A
114
13.920
35.103
8.727
1.00
11.55


887
CA
THR
A
114
13.271
35.294
10.024
1.00
12.41


888
CB
THR
A
114
14.165
34.776
11.162
1.00
11.80


889
OG1
THR
A
114
15.400
35.530
11.176
1.00
15.64


890
CG2
THR
A
114
14.494
33.307
10.927
1.00
14.91


891
C
THR
A
114
13.080
36.791
10.297
1.00
11.81


892
O
THR
A
114
13.647
37.683
9.603
1.00
11.26


893
N
ASP
A
115
12.274
37.124
11.291
1.00
11.36


894
CA
ASP
A
115
12.113
38.521
11.660
1.00
10.96


895
CB
ASP
A
115
11.017
38.718
12.737
1.00
12.92


896
CG
ASP
A
115
11.284
37.910
13.990
1.00
14.65


897
OD1
ASP
A
115
11.391
36.689
13.875
1.00
15.57


898
OD2
ASP
A
115
11.430
38.516
15.085
1.00
14.56


899
C
ASP
A
115
13.435
39.122
12.145
1.00
12.23


900
O
ASP
A
115
13.668
40.271
11.888
1.00
13.08


901
N
LYS
A
116
14.268
38.332
12.815
1.00
12.96


902
CA
LYS
A
116
15.574
38.838
13.282
1.00
14.53


903
CB
LYS
A
116
16.274
37.743
14.104
1.00
16.96


904
CG
LYS
A
116
17.641
38.212
14.659
1.00
24.00


905
CD
LYS
A
116
18.226
37.192
15.611
1.00
25.03


906
CE
LYS
A
116
18.633
35.953
14.896
1.00
38.30


907
NZ
LYS
A
116
19.573
36.227
13.785
1.00
42.73


908
C
LYS
A
116
16.418
39.234
12.065
1.00
14.20


909
O
LYS
A
116
17.060
40.305
12.037
1.00
15.23


910
N
GLU
A
117
16.416
38.400
11.035
1.00
14.02


911
CA
GLU
A
117
17.200
38.697
9.836
1.00
11.91


912
CB
GLU
A
117
17.287
37.465
8.956
1.00
12.83


913
CG
GLU
A
117
18.125
37.658
7.727
1.00
15.14


914
CD
GLU
A
117
19.629
37.853
8.066
1.00
20.85


915
OE1
GLU
A
117
20.090
37.378
9.121
1.00
23.10


916
OE2
GLU
A
117
20.312
38.479
7.263
1.00
21.25


917
C
GLU
A
117
16.576
39.865
9.084
1.00
15.14


918
O
GLU
A
117
17.291
40.687
8.509
1.00
14.51


919
N
ALA
A
118
15.236
39.972
9.067
1.00
12.70


920
CA
ALA
A
118
14.617
41.104
8.406
1.00
11.31


921
CB
ALA
A
118
13.038
40.949
8.428
1.00
12.66


922
C
ALA
A
118
15.021
42.426
9.092
1.00
12.16


923
O
ALA
A
118
15.262
43.422
8.399
1.00
12.80


924
N
ARG
A
119
15.059
42.443
10.411
1.00
13.29


925
CA
ARG
A
119
15.495
43.646
11.129
1.00
15.43


926
CB
ARG
A
119
15.282
43.522
12.639
1.00
16.04


927
CG
ARG
A
119
13.807
43.603
13.028
1.00
19.01


928
CD A
ARG
A
119
13.591
43.740
14.511
0.50
19.48


929
CD B
ARG
A
119
13.719
43.584
14.582
0.50
20.49


930
NE A
ARG
A
119
13.824
42.462
15.138
0.50
18.80


931
NE B
ARG
A
119
12.375
43.210
14.988
0.50
21.60


932
CZ A
ARG
A
119
12.932
41.468
15.209
0.50
14.46


933
CZ B
ARG
A
119
11.972
41.953
15.129
0.50
23.90


934
NH1A
ARG
A
119
11.689
41.594
14.704
0.50
13.01


935
NH1B
ARG
A
119
12.826
40.949
14.943
0.50
23.65


936
NH2A
ARG
A
119
13.317
40.329
15.745
0.50
15.29


937
NH2B
ARG
A
119
10.697
41.697
15.336
0.50
23.44


938
C
ARG
A
119
16.954
43.948
10.843
1.00
16.59


939
O
ARG
A
119
17.307
45.131
10.722
1.00
18.33


940
N
LYS
A
120
17.783
42.913
10.695
1.00
16.72


941
CA
LYS
A
120
19.206
43.113
10.407
1.00
17.81


942
CB
LYS
A
120
19.945
41.777
10.444
1.00
19.86


943
CG
LYS
A
120
21.441
41.907
10.270
1.00
22.47


944
CD
LYS
A
120
22.127
40.605
10.508
1.00
25.51


945
CE
LYS
A
120
23.622
40.805
10.517
1.00
29.10


946
NZ
LYS
A
120
24.238
39.467
10.455
1.00
27.57


947
C
LYS
A
120
19.353
43.759
9.049
1.00
19.84


948
O
LYS
A
120
20.127
44.721
8.886
1.00
20.84


949
N
ARG
A
121
18.587
43.256
8.086
1.00
16.16


950
CA
ARG
A
121
18.597
43.788
6.708
1.00
16.00


951
CB
ARG
A
121
18.041
42.747
5.732
1.00
14.54


952
CG
ARG
A
121
18.815
41.472
5.727
1.00
14.40


953
CD
ARG
A
121
18.223
40.465
4.767
1.00
15.26


954
NE
ARG
A
121
18.925
39.209
4.868
1.00
16.91


955
CZ
ARG
A
121
18.747
38.187
4.039
1.00
17.71


956
NH1
ARG
A
121
17.865
38.307
3.035
1.00
17.28


957
NH2
ARG
A
121
19.415
37.056
4.216
1.00
21.13


958
C
ARG
A
121
17.788
45.066
6.557
1.00
15.53


959
O
ARG
A
121
17.820
45.672
5.477
1.00
18.69


960
N
ASN
A
122
17.048
45.486
7.589
1.00
14.07


961
CA
ASN
A
122
16.243
46.708
7.514
1.00
17.04


962
CB
ASN
A
122
17.137
47.955
7.244
1.00
22.48


963
CG
ASN
A
122
18.320
48.072
8.239
1.00
29.06


964
OD1
ASN
A
122
18.130
48.029
9.454
1.00
28.68


965
ND2
ASN
A
122
19.547
48.221
7.703
1.00
27.29


966
C
ASN
A
122
15.150
46.621
6.464
1.00
18.23


967
O
ASN
A
122
14.860
47.594
5.774
1.00
18.73


968
N
VAL
A
123
14.536
45.447
6.341
1.00
16.71


969
CA
VAL
A
123
13.461
45.251
5.376
1.00
15.28


970
CB
VAL
A
123
13.843
44.253
4.282
1.00
13.67


971
CG1
VAL
A
123
15.122
44.801
3.503
1.00
17.85


972
CG2
VAL
A
123
14.122
42.824
4.878
1.00
13.19


973
C
VAL
A
123
12.160
44.770
6.038
1.00
12.69


974
O
VAL
A
123
12.162
44.216
7.132
1.00
17.06


975
N
GLY
A
124
11.069
44.998
5.329
1.00
17.32


976
CA
GLY
A
124
9.793
44.462
5.785
1.00
15.85


977
C
GLY
A
124
9.432
43.252
4.931
1.00
16.00


978
O
GLY
A
124
10.264
42.696
4.186
1.00
16.36


979
N
GLY
A
125
8.182
42.775
5.037
1.00
10.61


980
CA
GLY
A
125
7.835
41.654
4.192
1.00
9.89


981
C
GLY
A
125
6.506
41.030
4.638
1.00
9.46


982
O
GLY
A
125
5.906
41.495
5.600
1.00
10.75


983
N
GLU
A
126
6.039
40.049
3.903
1.00
9.36


984
CA
GLU
A
126
4.803
39.356
4.277
1.00
9.61


985
CB
GLU
A
126
4.271
38.551
3.071
1.00
11.09


986
CG
GLU
A
126
2.972
37.777
3.385
1.00
10.61


987
CD A
GLU
A
126
2.484
36.896
2.225
0.50
12.54


988
CD B
GLU
A
126
2.185
37.457
2.115
0.50
10.50


989
OE1A
GLU
A
126
1.489
36.172
2.438
0.50
12.17


990
OE1B
GLU
A
126
1.219
36.688
2.239
0.50
11.10


991
OE2A
GLU
A
126
3.085
36.928
1.122
0.50
16.76


992
OE2B
GLU
A
126
2.520
37.960
0.999
0.50
8.65


993
C
GLU
A
126
5.065
38.409
5.444
1.00
10.32


994
O
GLU
A
126
5.984
37.577
5.426
1.00
10.19


995
N
ILE
A
127
4.243
38.516
6.496
1.00
8.30


996
CA
ILE
A
127
4.435
37.661
7.668
1.00
8.50


997
CB
ILE
A
127
3.927
38.380
8.967
1.00
11.00


998
CG2
ILE
A
127
4.258
37.485
10.202
1.00
10.20


999
CG1
ILE
A
127
4.566
39.791
9.075
1.00
9.94


1000
CD1
ILE
A
127
6.081
39.758
9.113
1.00
11.70


1001
C
ILE
A
127
3.659
36.378
7.442
1.00
12.94


1002
O
ILE
A
127
2.459
36.309
7.583
1.00
12.22


1003
N
ILE
A
128
4.385
35.338
7.127
1.00
8.16


1004
CA
ILE
A
128
3.788
34.069
6.756
1.00
8.43


1005
CB
ILE
A
128
4.893
33.088
6.162
1.00
11.68


1006
CG2
ILE
A
128
4.278
31.664
5.893
1.00
15.27


1007
CG1
ILE
A
128
5.483
33.723
4.912
1.00
14.92


1008
CD1
ILE
A
128
6.709
32.916
4.404
1.00
15.70


1009
C
ILE
A
128
3.225
33.362
7.969
1.00
11.10


1010
O
ILE
A
128
2.098
32.815
7.928
1.00
11.36


1011
N
ALA
A
129
4.001
33.360
9.056
1.00
8.42


1012
CA
ALA
A
129
3.651
32.517
10.190
1.00
11.31


1013
CB
ALA
A
129
3.886
31.030
9.831
1.00
12.62


1014
C
ALA
A
129
4.538
32.857
11.358
1.00
11.70


1015
O
ALA
A
129
5.573
33.471
11.188
1.00
10.52


1016
N
TYR
A
130
4.128
32.376
12.524
1.00
12.71


1017
CA
TYR
A
130
4.912
32.503
13.772
1.00
11.06


1018
CB
TYR
A
130
4.096
33.153
14.884
1.00
9.73


1019
CG
TYR
A
130
3.810
34.647
14.798
1.00
13.43


1020
CD1
TYR
A
130
2.929
35.276
15.743
1.00
13.93


1021
CE1
TYR
A
130
2.711
36.649
15.720
1.00
12.86


1022
CD2
TYR
A
130
4.440
35.453
13.850
1.00
13.69


1023
CE2
TYR
A
130
4.206
36.814
13.815
1.00
12.21


1024
CZ
TYR
A
130
3.361
37.403
14.744
1.00
14.07


1025
OH
TYR
A
130
3.164
38.783
14.702
1.00
19.26


1026
C
TYR
A
130
5.197
31.077
14.232
1.00
12.06


1027
O
TYR
A
130
4.330
30.179
14.093
1.00
13.06


1028
N
VAL
A
131
6.384
30.847
14.761
1.00
12.37


1029
CA
VAL
A
131
6.746
29.545
15.321
1.00
10.90


1030
CB
VAL
A
131
7.705
28.725
14.383
1.00
12.13


1031
CG1
VAL
A
131
8.111
27.380
15.002
1.00
13.61


1032
CG2
VAL
A
131
6.977
28.472
13.036
1.00
13.82


1033
C
VAL
A
131
7.443
29.836
16.639
1.00
12.68


1034
O
VAL
A
131
8.233
30.741
16.707
1.00
12.17


1035
N
TRP
A
132
7.148
29.060
17.688
1.00
11.81


1036
CA
TRP
A
132
7.791
29.277
18.979
1.00
10.13


1037
CB
TRP
A
132
6.984
30.310
19.794
1.00
12.88


1038
CG
TRP
A
132
5.533
29.885
20.176
1.00
14.49


1039
CD2
TRP
A
132
4.353
29.986
19.348
1.00
13.75


1040
CE2
TRP
A
132
3.279
29.441
20.090
1.00
18.93


1041
CE3
TRP
A
132
4.108
30.484
18.058
1.00
15.41


1042
CD1
TRP
A
132
5.129
29.306
21.355
1.00
15.76


1043
NE1
TRP
A
132
3.787
29.049
21.303
1.00
18.78


1044
CZ2
TRP
A
132
1.975
29.369
19.589
1.00
19.22


1045
CZ3
TRP
A
132
2.803
30.412
17.548
1.00
18.59


1046
CH2
TRP
A
132
1.748
29.854
18.316
1.00
18.85


1047
C
TRP
A
132
7.888
27.986
19.747
1.00
13.45


1048
O
TRP
A
132
8.580
28.009
20.780
1.00
14.24


1049
OXT
TRP
A
132
7.328
26.956
19.320
1.00
12.97


1050
OH2
WAT
w
3
0.261
32.289
0.727
1.00
26.37


1051
OH2
WAT
W
4
18.155
41.673
14.092
1.00
22.07


1052
OH2
WAT
W
5
3.066
13.691
1.139
1.00
31.38


1053
OH2
WAT
W
6
−2.001
26.219
10.471
1.00
17.18


1054
OH2
WAT
W
7
−3.962
21.533
14.199
1.00
24.79


1055
OH2
WAT
W
9
−4.219
27.772
10.372
1.00
22.54


1056
OH2
WAT
W
10
16.168
22.783
−3.704
1.00
40.38


1057
OH2
WAT
W
11
9.463
12.123
32.594
1.00
26.12


1058
OH2
WAT
W
15
7.517
46.701
0.692
1.00
28.15


1059
OH2
WAT
W
16
15.058
28.701
3.574
1.00
19.86


1060
OH2
WAT
W
17
7.778
8.089
14.852
1.00
34.39


1061
OH2
WAT
W
18
11.071
29.126
20.872
1.00
14.13


1062
OH2
WAT
W
21
5.925
27.933
−3.858
1.00
23.69


1063
OH2
WAT
W
22
17.743
35.692
1.568
1.00
23.60


1064
OH2
WAT
W
23
7.425
8.969
12.487
1.00
35.37


1065
OH2
WAT
W
24
−9.657
32.414
7.871
1.00
49.96


1066
OH2
WAT
W
27
−4.630
36.813
7.612
1.00
15.21


1067
OH2
WAT
W
28
14.275
36.488
−5.206
1.00
17.71


1068
OH2
WAT
W
30
−10.848
38.870
1.955
1.00
25.53


1069
OH2
WAT
W
31
0.258
18.619
24.130
1.00
30.00


1070
OH2
WAT
W
33
20.547
24.643
16.358
1.00
38.93


1071
OH2
WAT
W
34
2.932
31.091
−1.203
1.00
32.87


1072
OH2
WAT
W
35
13.726
13.258
31.530
1.00
16.96


1073
OH2
WAT
W
36
9.272
47.892
4.417
1.00
27.08


1074
OH2
WAT
W
38
18.453
24.784
6.373
1.00
33.48


1075
OH2
WAT
W
39
16.016
33.339
−2.654
1.00
21.68


1076
OH2
WAT
W
40
9.305
10.547
18.786
1.00
29.41


1077
OH2
WAT
W
41
16.215
43.320
−0.448
1.00
21.67


1078
OH2
WAT
W
43
−6.859
22.079
2.725
1.00
45.81


1079
OH2
WAT
W
44
1.105
13.913
2.759
1.00
37.15


1080
OH2
WAT
W
45
2.068
33.869
3.100
1.00
17.17


1081
OH2
WAT
W
46
9.123
25.869
22.179
1.00
15.32


1082
OH2
WAT
W
47
14.820
31.217
2.423
1.00
19.05


1083
OH2
WAT
W
48
15.352
13.453
23.126
1.00
36.77


1084
OH2
WAT
W
49
15.393
21.125
30.136
1.00
28.18


1085
OH2
WAT
W
50
10.067
35.302
−0.416
1.00
16.41


1086
OH2
WAT
W
52
6.479
39.660
20.953
1.00
29.28


1087
OH2
WAT
W
53
3.557
11.517
7.070
1.00
27.25


1088
OH2
WAT
W
54
21.164
16.162
27.968
1.00
32.52


1089
OH2
WAT
W
55
16.536
20.422
25.510
1.00
31.71


1090
OH2
WAT
W
56
10.272
19.641
15.854
1.00
14.72


1091
OH2
WAT
W
58
8.893
12.169
21.730
1.00
31.16


1092
OH2
WAT
W
59
17.216
35.031
−4.063
1.00
23.65


1093
OH2
WAT
W
61
13.867
22.615
28.037
1.00
27.42


1094
OH2
WAT
W
62
6.823
52.637
12.444
1.00
38.27


1095
OH2
WAT
W
63
12.660
25.624
20.931
1.00
29.04


1096
OH2
WAT
W
65
9.179
19.611
18.377
1.00
12.64


1097
OH2
WAT
W
66
12.788
26.455
−2.296
1.00
21.40


1098
OH2
WAT
W
68
1.620
13.251
10.080
1.00
33.25


1099
OH2
WAT
W
71
16.232
41.515
16.169
1.00
26.22


1100
OH2
WAT
W
74
4.087
10.020
−1.602
1.00
35.87


1101
OH2
WAT
W
76
1.542
24.687
−3.416
1.00
30.17


1102
OH2
WAT
W
83
3.523
8.602
19.487
1.00
16.30


1103
OH2
WAT
W
86
11.210
46.885
3.041
1.00
26.46


1104
OH2
WAT
W
87
19.040
30.033
2.757
1.00
42.90


1105
OH2
WAT
W
89
1.184
23.315
19.085
1.00
19.00


1106
OH2
WAT
W
92
12.801
45.216
9.729
1.00
21.02


1107
OH2
WAT
W
93
18.293
19.615
22.198
1.00
41.60


1108
OH2
WAT
W
94
17.487
34.488
12.316
1.00
22.73


1109
OH2
WAT
W
95
−7.069
36.729
8.954
1.00
22.21


1110
OH2
WAT
W
97
−6.520
27.123
5.883
1.00
27.24


1111
OH2
WAT
W
98
10.994
10.078
−9.567
1.00
37.87


1112
OH2
WAT
W
99
19.626
34.512
8.612
1.00
40.75


1113
OH2
WAT
W
101
1.015
16.289
25.198
1.00
15.37


1114
OH2
WAT
W
102
0.276
25.494
17.431
1.00
15.36


1115
OH2
WAT
W
103
2.139
20.825
18.331
1.00
15.98


1116
OH2
WAT
W
104
16.691
34.142
8.038
1.00
17.77


1117
OH2
WAT
W
105
−2.802
28.998
12.507
1.00
19.40


1118
OH2
WAT
W
106
6.285
25.347
−6.096
1.00
20.12


1119
OH2
WAT
W
107
10.723
37.111
17.353
1.00
16.57


1120
OH2
WAT
W
108
1.745
19.796
20.994
1.00
20.57


1121
OH2
WAT
W
109
2.983
26.279
−1.443
1.00
22.32


1122
OH2
WAT
W
110
7.048
22.458
24.019
1.00
19.45


1123
OH2
WAT
W
111
−1.785
36.791
1.344
1.00
27.44


1124
OH2
WAT
W
112
3.107
21.974
22.207
1.00
23.19


1125
OH2
WAT
W
113
−5.384
29.592
5.922
1.00
20.68


1126
OH2
WAT
W
114
0.554
15.364
10.840
1.00
20.38


1127
OH2
WAT
W
115
16.165
27.477
1.361
1.00
28.18


1128
OH2
WAT
W
116
14.556
47.250
10.297
1.00
22.90


1129
OH2
WAT
W
117
18.154
21.823
13.453
1.00
28.48


1130
OH2
WAT
W
118
15.610
40.135
2.416
1.00
21.57


1131
OH2
WAT
W
120
9.946
38.683
27.554
1.00
22.08


1132
OH2
WAT
W
121
13.699
35.927
14.523
1.00
21.15


1133
OH2
WAT
W
122
1.632
28.671
−1.043
1.00
25.21


1134
OH2
WAT
W
123
14.933
14.669
18.467
1.00
22.96


1135
OH2
WAT
W
124
16.737
47.364
11.299
1.00
29.14


1136
OH2
WAT
W
125
−3.093
19.738
7.218
1.00
23.07


1137
OH2
WAT
W
126
10.379
33.025
−1.744
1.00
25.17


1138
OH2
WAT
W
127
9.954
25.754
24.878
1.00
22.93


1139
OH2
WAT
W
128
13.853
33.965
−4.009
1.00
25.23


1140
OH2
WAT
W
129
−0.809
29.646
0.277
1.00
24.06


1141
OH2
WAT
W
130
9.502
51.180
7.807
1.00
25.54


1142
OH2
WAT
W
131
13.068
48.612
2.146
1.00
27.48


1143
OH2
WAT
W
132
14.127
42.274
0.839
1.00
23.95


1144
OH2
WAT
W
133
13.134
13.190
14.286
1.00
23.18


1145
OH2
WAT
W
134
15.159
12.904
20.597
1.00
26.16


1146
OH2
WAT
W
135
10.440
23.032
24.629
1.00
23.66


1147
OH2
WAT
W
136
−3.713
37.445
−0.713
1.00
28.18


1148
OH2
WAT
W
137
0.604
21.676
2.201
1.00
25.71


1149
OH2
WAT
W
138
1.066
37.345
−1.106
1.00
34.42


1150
OH2
WAT
W
139
16.905
23.452
19.180
1.00
34.87


1151
OH2
WAT
W
140
4.185
36.771
20.480
1.00
40.00


1152
OH2
WAT
W
142
10.914
13.273
30.854
1.00
24.89


1153
OH2
WAT
W
143
3.873
16.101
−4.915
1.00
28.61


1154
OH2
WAT
W
144
11.111
36.927
25.805
1.00
25.96


1155
OH2
WAT
W
145
13.608
12.384
16.901
1.00
23.49


1156
OH2
WAT
W
146
−0.954
11.414
−9.353
1.00
36.01


1157
OH2
WAT
W
147
16.603
32.573
5.264
1.00
23.66


1158
OH2
WAT
W
148
12.092
41.853
23.010
1.00
25.81


1159
OH2
WAT
W
149
11.751
10.811
17.753
1.00
27.61


1160
OH2
WAT
W
150
17.393
29.734
4.814
1.00
33.79


1161
OH2
WAT
W
151
16.056
33.961
14.670
1.00
30.25


1162
OH2
WAT
W
152
−1.210
27.071
19.148
1.00
28.86


1163
OH2
WAT
W
153
−6.321
36.116
11.372
1.00
33.09


1164
OH2
WAT
W
154
2.148
47.680
13.303
1.00
25.86


1165
OH2
WAT
W
155
14.992
11.270
27.745
1.00
31.33


1166
OH2
WAT
W
156
−1.274
22.960
20.245
1.00
29.25


1167
OH2
WAT
W
157
1.590
28.270
23.231
1.00
33.45


1168
OH2
WAT
W
158
12.847
26.022
−7.530
1.00
29.22


1169
OH2
WAT
W
159
4.214
11.114
1.150
1.00
24.17


1170
OH2
WAT
W
160
−1.655
11.811
13.568
1.00
29.91


1171
OH2
WAT
W
161
2.666
20.185
−4.292
1.00
38.55


1172
OH2
WAT
W
162
14.926
31.740
−1.411
1.00
28.82


1173
OH2
WAT
W
163
15.004
47.207
13.602
1.00
42.80


1174
OH2
WAT
W
164
14.059
33.176
18.340
1.00
27.02


1175
OH2
WAT
W
165
10.371
7.912
−3.670
1.00
43.64


1176
OH2
WAT
W
166
−5.215
23.809
8.874
1.00
30.82


1177
OH2
WAT
W
167
−1.687
21.400
0.893
1.00
32.38


1178
OH2
WAT
W
168
5.863
41.998
26.689
1.00
36.28


1179
OH2
WAT
W
169
18.586
43.498
2.324
1.00
41.21


1180
OH2
WAT
W
170
9.137
22.594
27.102
1.00
27.05


1181
OH2
WAT
W
171
19.822
37.167
11.677
1.00
33.36


1182
OH2
WAT
W
172
12.631
24.517
−4.342
1.00
31.01


1183
OH2
WAT
W
173
20.730
24.100
8.177
1.00
37.46


1184
OH2
WAT
W
174
22.422
39.621
6.823
1.00
34.02


1185
OH2
WAT
W
175
3.034
33.133
0.552
1.00
35.38


1186
OH2
WAT
W
176
20.107
21.863
5.289
1.00
39.46


1187
OH2
WAT
W
177
17.163
31.964
1.388
1.00
42.30


1188
OH2
WAT
W
178
12.187
29.146
−3.563
1.00
31.78


1189
OH2
WAT
W
179
−6.222
25.258
3.777
1.00
28.97


1190
OH2
WAT
W
180
12.001
47.032
13.002
1.00
29.82


1191
OH2
WAT
W
181
22.795
37.299
9.451
1.00
42.30


1192
OH2
WAT
W
182
−7.525
30.698
4.806
1.00
36.37


1193
OH2
WAT
W
183
−5.215
29.584
8.649
1.00
30.25


1194
OH2
WAT
W
184
19.872
33.405
−4.183
1.00
36.05


1195
OH2
WAT
W
185
4.744
20.991
24.051
1.00
25.27


1196
OH2
WAT
W
186
11.400
11.709
22.297
1.00
28.93


1197
OH2
WAT
W
187
−9.057
34.780
8.847
1.00
33.56


1198
OH2
WAT
W
188
−2.249
15.984
10.194
1.00
32.98


1199
OH2
WAT
W
189
−2.884
24.955
19.234
1.00
36.03


1200
OH2
WAT
W
190
9.696
50.530
4.968
1.00
35.77


1201
OH2
WAT
W
191
21.019
30.872
11.346
1.00
38.17


1202
OH2
WAT
W
192
14.204
30.960
21.968
1.00
25.74


1203
OH2
WAT
W
193
−7.976
32.734
3.191
1.00
36.90


1204
OH2
WAT
W
194
14.461
50.113
6.091
1.00
29.97


1205
OH2
WAT
W
195
17.801
16.321
21.589
1.00
36.20


1206
OH2
WAT
W
197
18.581
44.348
14.054
1.00
30.95


1207
OH2
WAT
W
198
2.731
12.003
−3.103
1.00
33.47


1208
OH2
WAT
W
199
14.447
21.324
23.946
1.00
37.36


1209
OH2
WAT
W
200
−4.238
31.779
12.341
1.00
29.12


1210
OH2
WAT
W
201
4.514
2.957
12.647
1.00
44.36


1211
OH2
WAT
W
203
0.642
19.740
3.863
1.00
38.63


1212
OH2
WAT
W
205
6.790
9.078
−2.562
1.00
40.08


1213
OH2
WAT
W
206
4.797
31.295
−3.250
1.00
33.26


1214
OH2
WAT
W
207
20.687
40.871
14.582
1.00
43.83


1215
OH2
WAT
W
211
19.926
29.795
15.512
1.00
44.11


1216
OH2
WAT
W
212
−2.671
29.660
−1.627
1.00
31.81


1217
OH2
WAT
W
213
15.587
48.423
3.075
1.00
30.76


1218
OH2
WAT
W
214
17.679
19.494
4.704
1.00
40.20


1219
OH2
WAT
W
215
14.957
25.819
0.027
1.00
33.37


1220
OH2
WAT
W
216
15.118
34.866
16.687
1.00
36.89


1221
OH2
WAT
W
217
−6.271
21.840
12.594
1.00
43.41


1222
OH2
WAT
W
218
7.913
37.111
26.296
1.00
42.81


1223
OH2
WAT
W
219
19.415
14.734
23.625
1.00
33.68


1224
OH2
WAT
W
220
17.263
9.938
−8.670
1.00
43.05


1225
OH2
WAT
W
221
7.507
8.481
0.718
1.00
42.02


1226
OH2
WAT
W
222
12.412
51.527
8.293
1.00
39.48


1227
OH2
WAT
W
223
−4.213
17.630
16.081
1.00
28.56


1228
OH2
WAT
W
225
13.627
8.137
6.246
1.00
45.87


1229
OH2
WAT
W
226
13.553
49.899
10.508
1.00
42.09


1230
OH2
WAT
W
227
1.479
51.259
7.651
1.00
36.49


1231
OH2
WAT
W
229
−6.368
26.008
8.421
1.00
35.35


1232
OH2
WAT
W
230
20.435
12.355
2.203
1.00
40.09


1233
OH2
WAT
W
231
18.153
28.461
6.720
1.00
44.41


1234
OH2
WAT
W
232
20.764
46.715
10.993
1.00
47.11


1235
OH2
WAT
W
233
4.419
8.228
−5.884
1.00
37.01


1236
OH2
WAT
W
234
−5.554
18.749
11.830
1.00
41.82


1237
OH2
WAT
W
235
8.115
47.714
15.867
1.00
40.18


1238
OH2
WAT
W
236
6.870
26.198
25.697
1.00
34.10


1239
OH2
WAT
W
237
10.662
45.778
14.817
1.00
35.68


1240
OH2
WAT
W
238
14.400
26.566
18.363
1.00
32.18


1241
OH2
WAT
W
240
3.335
45.023
0.285
1.00
38.84


1242
OH2
WAT
W
241
2.751
7.228
6.330
1.00
50.85


1243
OH2
WAT
W
242
5.710
37.994
25.220
1.00
37.91


1244
OH2
WAT
W
243
20.700
19.007
3.691
1.00
39.90


1245
OH2
WAT
W
244
19.908
16.572
17.568
1.00
56.94


1246
OH2
WAT
W
246
4.431
38.416
22.728
1.00
42.21


1247
OH2
WAT
W
247
8.317
9.182
6.964
1.00
54.58


1248
OH2
WAT
W
248
15.498
10.503
24.116
1.00
46.07


1249
OH2
WAT
W
249
14.443
8.663
−9.508
1.00
38.83


1250
OH2
WAT
W
250
0.806
46.599
2.414
1.00
38.84


1251
OH2
WAT
W
251
15.869
30.188
16.379
1.00
38.11


1252
OH2
WAT
W
252
7.352
28.899
−6.950
1.00
66.38


1253
OH2
WAT
W
254
−4.943
12.924
7.071
1.00
46.90


1254
OH2
WAT
W
255
−0.389
20.369
25.846
1.00
34.19


1255
OH2
WAT
W
256
19.975
48.181
4.575
1.00
41.62


1256
OH2
WAT
W
257
−3.747
29.175
−5.942
1.00
46.12


1257
OH2
WAT
W
258
17.067
29.492
0.012
1.00
45.57


1258
OH2
WAT
W
259
−5.841
26.305
11.606
1.00
44.57


1259
OH2
WAT
W
261
3.022
47.371
8.159
1.00
27.51


1260
OH2
WAT
W
262
6.150
29.001
24.769
1.00
27.00


1261
OH2
WAT
W
264
2.492
49.167
6.241
1.00
31.67


1262
OH2
WAT
W
265
18.777
45.611
3.013
1.00
32.27


1263
OH2
WAT
W
266
−11.514
36.131
7.903
1.00
33.94


1264
OH2
WAT
W
267
21.566
38.893
13.622
1.00
36.54


1265
OH2
WAT
W
269
15.298
19.519
28.683
1.00
51.15


1266
OH2
WAT
W
270
19.792
27.338
15.438
1.00
41.61


1267
OH2
WAT
W
271
15.581
11.901
13.471
1.00
33.75


1268
OH2
WAT
W
272
17.242
12.516
9.236
1.00
40.12


1269
OH2
WAT
W
273
−6.961
15.515
12.385
1.00
34.15


1270
OH2
WAT
W
274
19.422
14.241
27.137
1.00
46.30


1271
OH2
WAT
W
283
11.632
7.314
0.873
1.00
37.15


1272
OH2
WAT
W
285
3.527
24.309
−6.074
1.00
37.02


1273
OH2
WAT
W
286
2.752
33.234
20.239
1.00
40.00


1274
OH2
WAT
W
287
1.873
2.010
11.965
1.00
38.57


1275
OH2
WAT
W
288
18.284
30.464
10.373
1.00
44.52


1276
OH2
WAT
W
289
−0.575
17.304
3.770
1.00
36.81


1277
OH2
WAT
W
290
−4.610
26.297
15.067
1.00
43.10


1278
OH2
WAT
W
291
−10.059
35.001
1.831
1.00
38.83


1279
OH2
WAT
W
292
17.153
31.957
−4.434
1.00
38.60


1280
OH2
WAT
W
302
6.023
49.650
2.731
1.00
37.67


1281
OH2
WAT
W
303
21.385
13.626
28.217
1.00
35.56


1282
OH2
WAT
W
304
9.966
48.081
18.517
1.00
41.63


1283
OH2
WAT
W
305
−1.894
34.203
−0.825
1.00
41.23


1284
OH2
WAT
W
306
17.745
15.877
18.835
1.00
43.82


1285
OH2
WAT
W
307
18.401
15.878
2.446
1.00
52.53


1286
OH2
WAT
W
311
14.094
37.698
17.136
1.00
42.65


1287
OH2
WAT
W
312
3.354
11.493
10.405
1.00
45.24


1288
OH2
WAT
W
313
12.941
11.084
20.255
1.00
34.51


1289
OH2
WAT
W
314
−3.497
28.364
14.837
1.00
36.86


1290
OH2
WAT
W
315
3.319
36.874
26.026
1.00
41.44


1291
OH2
WAT
W
316
13.467
27.722
20.512
1.00
43.33


1292
OH2
WAT
W
317
17.053
25.876
19.181
1.00
45.68


1293
OH2
WAT
W
318
13.795
30.880
18.217
1.00
39.19


1294
OH2
WAT
W
319
−9.397
37.499
9.389
1.00
53.51


1295
OH2
WAT
W
321
1.652
0.597
14.057
1.00
36.90


1296
OH2
WAT
W
322
−6.598
30.034
−1.987
1.00
49.18


1297
OH2
WAT
W
323
12.454
23.087
24.086
1.00
41.19


1298
OH2
WAT
W
326
16.710
42.206
1.767
1.00
64.24


1299
OH2
WAT
W
327
10.083
29.660
−2.635
1.00
51.02


1300
OH2
WAT
W
328
−7.804
30.392
9.431
1.00
39.03


1301
OH2
WAT
W
330
22.466
48.916
2.705
1.00
48.85


1302
OH2
WAT
W
335
1.496
21.993
−2.407
1.00
38.10


1303
OH2
WAT
W
336
18.283
33.498
10.149
1.00
42.45


1304
OH2
WAT
W
337
4.233
30.289
25.277
1.00
42.76


1305
OH2
WAT
W
342
24.038
47.844
0.868
1.00
39.88


1306
OH2
WAT
W
344
16.813
14.879
0.411
1.00
41.75


1307
OH2
WAT
W
345
5.438
7.866
15.715
1.00
52.84


1308
OH2
WAT
W
346
16.291
23.734
−1.125
1.00
39.55


1309
OH2
WAT
W
347
13.025
9.450
−3.178
1.00
44.56


1310
OH2
WAT
W
349
14.233
22.340
2.733
1.00
50.22


1311
OH2
WAT
W
350
12.227
23.367
26.694
1.00
47.09


1312
OH2
WAT
W
351
18.563
36.730
−4.783
1.00
64.01


1313
OH2
WAT
W
352
4.655
14.983
26.660
1.00
25.91


1314
OH2
WAT
W
353
13.122
7.856
19.736
1.00
41.94


1315
OH2
WAT
W
354
−8.723
27.271
10.140
1.00
45.47


1316
OH2
WAT
W
355
21.589
17.424
5.171
1.00
48.12


1317
OH2
WAT
W
356
14.998
11.204
30.356
1.00
36.89


1318
OH2
WAT
W
357
−0.410
34.681
0.810
1.00
41.71


1319
OH2
WAT
W
358
1.781
24.032
17.043
1.00
50.64


1320
OH2
WAT
W
359
0.847
18.603
22.240
1.00
45.03


1321
OH2
WAT
W
360
13.105
36.160
−3.586
1.00
50.05


1322
OH2
WAT
W
361
−0.679
20.082
20.448
1.00
46.12


1323
OH2
WAT
W
362
11.784
45.772
1.769
1.00
41.27


1324
OH2
WAT
W
363
−1.314
36.478
−0.558
1.00
45.13


1325
OH2
WAT
W
364
17.040
12.298
27.168
1.00
46.18


1326
OH2
WAT
W
365
6.404
26.395
17.529
1.00
48.11


1327
OH2
WAT
W
366
13.011
50.732
13.200
1.00
39.87


1328
OH2
WAT
W
367
22.712
37.399
16.781
1.00
42.06


1329
OH2
WAT
W
368
18.576
33.861
3.979
1.00
40.44


1330
OH2
WAT
W
369
1.340
17.351
−4.937
1.00
40.33

## Claims

1. A composition comprising a Staphylococcus aureus S8 rRNA-binding protein (SEQ ID NO:1) in orthorhombic crystalline form, wherein the crystalline form has lattice constants of a=42.1 Å, b=55.9 Å, c=61.3 Å, α=90.0°, β=90.0°, γ=90.0°.

2. The composition according to claim 1 wherein the crystalline form contains a Staphylococcus aureus S8 rRNA-binding protein (SEQ ID NO:1) molecule in the asymmetric unit.

3. The composition according to claim 1 wherein said Staphylococcus aureus S8 rRNA-binding protein (SEQ ID NO:1) has an active site cavity formed by the amino acids S107, T108, S109, and E126.

4. A method for the production of a Staphylococcus aureus S8 rRNA-binding protein in orthorhombic crystalline form having a space group of P212121, said method comprising:
a) forming sitting drops by mixing Staphylococcus aureus S8 rRNA-binding protein with a reservoir solution at about pH 8.5, said reservoir solution further comprises 30% PEG4000, 0.2M Li2SO4, and 0.1M Tris-HCl; and
b) equilibrating said sitting drops at room temperature.