CA2390971A1

CA2390971A1 - Identification of compounds for inhibiting mta/adohcy nucleosidases

Info

Publication number: CA2390971A1
Application number: CA 2390971
Authority: CA
Inventors: Lynne Howell; Jeffrey Ernest Lee
Original assignee: Individual
Current assignee: Hospital for Sick Children HSC
Priority date: 2001-07-19
Filing date: 2002-07-19
Publication date: 2003-01-19

Abstract

The invention includes the 3D structure of MTA/AdoHcy nucleosidases. It also includes methods of identifying compounds that modulate MTA/AdoHcy nucleosidase activity by producing a compound that interacts with all or part of the 3D
structure of MTA/AdoHcy nucleosidase or a fragment or derivative thereof and which thereby modulates MTA/AdoHcy nucleosidase activity.

Description

DEMANDES OU BREVETS VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDS OU CE BREVETS
COMPREND PLUS D'UN TOME.
CECI EST LE TOME ~ DE J
NOTE: Pour les tomes additionels, veillez contacter 1e Bureau Canadien des Brevets.
JUMBO APPLICATIONS / PATENTS
THIS SECTION OF THE APPLICATION / PATENT CONTAINS MORE
THAN ONE VOLUME.
THIS IS VOLUME T OF
NOTE: For additional volumes please contact the Canadian Patent Office.

Identification of Compounds for Inhibiting MTAIAdoHcy nucleosidases Field of the Invention The invention relates to methods of using the three dimensional structure of a MTA/AdoHcy nucleosidase, preferably the E. co/i, S. aunsus or S. pneumoniae MTA/AdoHcy nucleosidase, to identify candidate compounds that will interact with a MTA/AdoHcy nucleosidase and inhibit its activity. The invention also includes compounds identified using the methods of the invention.
~ckground of the Invention The enzyme 5'-methylthioadenosine/S-adenosylhomocysteine (MTAIAdoHcy) nucleosidase (E.G. 3.2.2.9) catalyzes the hydrolysis of the glycosidic bond of 5'-methylthioadenosine (MTA) and S-adenosylhomocysteine (AdoHcy) to adenine and its corresponding thioribose [1 ). The reaction is irreversible with K", = 0.43 p.M and 4.3 ~M
for MTA and AdoHcy, respectively [2, 3).
MTA/AdoHcy nucleosidase represents an attractive target for the design of antimicrobial drugs. An exploitable metabolic difference exists in how the nucleosides, 5'-methylthioadenosine (MTA) and S-adenosylhamocysteine (AdoHcy) are catabolized in mammalian and microbial cells [4, 5). In mammalian cells and some microorganisms, the breakdown of MTA and AdoHcy requires two separate enzymes. MTA is catabolized in a reversible reaction to adenine and 5'-methylthioribose-1-phosphate (MTR-1-P) by MTA phosphorylase (MTAP), while AdoHcy is broken down to homocysteine and adenosine by AdoHcy hydrolase [6). In contrast, in microbes that are devoid of MTAP and AdoHcy hydrolase, the dual substrate-specific MTA/AdoHcy nucleosidase functions to recycle both nucleosides.
MTA and AdoHcy are critical for the regulation of ceNular processes such as protein and DNA methylation [7), polyamine synthesis [8, 9), CAMP metabolism [10], and cytokine secretion [11). In transmethylation reactions, S-adenosylmethionine (AdoMet) is converted to AdoHcy when the activated methyl group is transferred to a recipient molecule [12). AdoHcy is a potent feedback inhibitor of AdoMet dependent methylation reactions. Inhibition of MTA/AdoHcy nucleosidase would therefore increase cellular levels of AdoHcy thereby inhibiting biological methylation. MTA on the other hand is primarily obtained as a consequence of polyamine biosynthesis. In polyamine biosynthesis, AdoMet is first decarboxylated and then the propylamine group is transferred to form the polyamines, spermine and spermidine. MTA is a co-product of the polyamine synthase reactions and exerts a potent feedback inhibition of these enzymes at low micromolar concentrations [8, 9]. To avoid an inhibitory intracellular buildup of MTA, it rapidly enters a recycling pathway where it is salvaged to methionine and adenine [5]. In many prokaryotes, the entry into the recycling pathway occurs through the combined action of two enzymes, MTAIAdoHcy nucleosidase and 5'-methylthioribose (MTR) kinase. These finro enzymes respectively catalyze the irreversible hydrolytic cleavage of MTA to MTR and adenine, and the subsequent ATP-dependent phosphorylation of MTR to MTR-1-P. In contrast, in mammalian cells MTA is degraded in a single phosphorylytic cleavage to MTR-1-P and adenine.
Inhibition of MTA/AdoHcy nucleosidase would block the recycling of MTA and cause a build up of intracellular MTA levels, leading to inhibition of polyamine synthesis. Taken together, the critical nature of the nucleosidase in the functioning of finro pathways that are crucial for cell survival points to this enzyme as a logical target for structure-based drug design of broad-spectrum antimicrobial agents.
MTAIAdoHcy nucleosidase activity has been observed in a number of prokaryotic species including E. coli, B. subtilis, K. pneumoniae, and G. lamblia. The enzyme has subsequently been purified from several bacterial and plant species [3, 13-16].
The E. coli MTAIAdoHcy nucleosidase monomer contains 232 residues and has a molecular weight of 25.5 kDa [2, 3, 13]. The enzyme is active over a broad range of pH and temperature, with mildly acidic conditions and temperatures of 37-45 °C being the optimal [3]. The nucleosidase species sequenced to date exhibit between 27%
56% amino acid identity. A computational search of the sequence database reveals a lack of significant similarity to any known protein [2], although residues 69-91 of the MTA/AdoHcy nucieosidase do share high sequence similarity (73% with conservative substitutions) to human purine nucleoside phosphorylase (PNP). Residues 69-91 belong to the active site region of human PNP [17].
Inhibitors of MTAIAdoHcy nucleosidase are known, such as Formycin A (FMA) and 5'-methylthiotubercidin (M'rn, but their precise mecharrNSm of action is not known.
Neither compound has been exploited as a therapeutic compound. An effective therapeutic for humans must inhibit the bacterial MTAIAdoHcy nucleosidase while not affecting activity of the human MTA phosphorylase or AdoHcy hydrolase. This selectivity must currently be identified largely by trial and error with assays. Since there is no way of knowing the interactions at the molecular level, it is possible that a MTA/AdoHcy nucleosidase inhibitor affects MTA phosphorylase or AdoHcy hydrolase function. This may not be apparent until clinical trials are pertormed or until after a drug is marketed. Without a 3D structure, he risk of affecting human enzyme activity remains a barrier to development of selective MTA/AdoHcy nucleosidase inhibitors.

It would be ideal if one could determine the MTA/AdoHcy nucleosidase 3D
structure and catalytic mechanism. This would permit determination of the molecular interactions between a potential inhibitor and each of MTA/AdoHcy nucleosidase and MTA phosphorylase or AdoHcy hydrolase. Selective inhibitors could then be designed for treatment of bacterial disease. However, there remains a need for crystallization and X-ray analysis of recombinant E. coli MTA/AdoHcy nucleosidase in order to determine the MTA/AdoHcy nuclsosidase 3D.
Summary of the Invention The invention relates to the 3D structure of MTA/AdoHcy nucleosidases.
Structures have been determined for E. coli, S. aureus and S. pneumoniae MTAIAdoHcy nucleosidases in the presence of substrate and transition state analogs. These MTA/AdoHcy nucleosidase structures provide a detailed description of its active site and a simple model fortheenzyme activity.
Now that the three-dimensional structure of the nucleosidase crystal has been determined, an inhibitor of nucleosidase can be identfied through the use of rational drug design by computer modeling with a docking program. This procedure can inGude computer fitting of potential inhibitors to the nucleosidase to ascertain how well the shape and the chemical structure of the potential modulator will bind to either the individual bound subunits or to the entire nucleosidase. Computer programs can z0 also be employed to estimate the attraction, repulsion, and steric hindrance of the subunits with a modulator/inhibitor.
A particular advantage is that selective inhibitors can be ident~ed by comparing the potential inhibitor to the 3D structure of MTA phosphorylase and/or AdoHcy hydrolase or individual bound subunits.
The E. coli MTAIAdoHcy nucleosidase monomer consists of a mixed alai domain with a nine-stranded mixed (3-sheet, flanked by six a-helices and a small 3,o helix.
Intersubunit contacts between the two monomers present in the asymmetric unit are mediated primarily by helix-helix and helix-loop hydrophobic interactions. The presence of an adenine molecule in the active site of the enzyme has allowed the identification of both substrate binding and catalytic amino acid residues.
Although the sequence of E. coil MTAIAdoHcy nucleosidase has almost no identity with any known enzyme, its tertiary structure is similar to both the mammaban (trimeric) and prokaryotic (hexameric) purine nucleoside phosphorylases. The structure provides evidence that this protein is functional as a dimer and that the dual specificity for MTA and AdoHcy results from the truncation of a helix. The structure of MTA/AdoHcy nucleosidase is the first structure of a prokaryotic nucleoside N-ribohydrolase specific for 6-aminopurines.
The crystal structures of E. coli MTA/AdoHcy nucleosidase complexed with the transition state analogs, Formycin A (FMA) and 5'-methylthiotubercidin (MTT) have been solved to 2.2 A, and 2.0 A resolution, respectively. In addition, a crystal structure of an E. coli MTA/AdoHcy nucleosidase mutant (E12A) has been determined in complex with its natural substrate, AdoHcy. These are the first MTA/AdoHcy nucleosidase structures to be solved in the presence of a transition state inhibitor. These structures clearly identify the residues involved in substrate binding and catalysis in the active site. Comparisons of the transition state inhibitor-compiexes to the adenine-bound MTA/AdoHcy nucleosidase structure provide structural evidence for a ligand-induced conformational change in the active site and its substrate preference.
The invention includes a crystal comprising MTAIAdoHcy nucleosidase.
Accordingly, the invention also includes a method of identifying a compound that modulates (ie. increases or decreases) MTA/AdoHcy nucleosidase activity, comprising obtaining a 3D structure of MTA/AdoHcy nucleosidase or fragment thereof, designing a compound to interact with the 3D structure of MTA/AdoHcy nucleosidase or fragment thereof, obtaining the compound, and determining whether the compound affects MTA/AdoHcy nucleosidase activity. The designing may be by comparison of a known compound structure or by design (assembly) of a new or known compound structure. The 3D structure of MTA/AdoHcy nucleosidase or fragment thereof preferably comprises at least one of i) an active site ii) a 5' binding cavity and iii) a ribose binding site. Designing a compound optionally comprises comparing the structural coordinates of the compound to the structural coordinates of at least one of i) to iii) and determining whether the compound fits spatially into at least one of i) to iii) and is capable of a) changing MTA/AdoHcy nucleosidase from an open conformation to a closed conformation without nucleoside catalysis;
b) biasing MTA/AdoHcy nucleosidase toward a closed conformation; or c) preventing MTAIAdoHcy nucleosidase from changing toward a transition conformation or a closed conformation; wherein the ability of the compound to cause any of a) to c) indicates that the compound inhibits MTAIAdoHcy nucleosidase activity. The 3D structure is preferably determined from one or more sets of structural coordinates in Tables 1 to 6. The method preferably further comprisess introducing into a computer program the aforementioned structural coordinates defining an MTAIAdoHcy nucleosidase, wherein the program generates the 3D
structure of the MTA/AdoHcy nucleosidase. The MTAIAdoHcy nucleosidase preferably comprises all or part of an amino acid sequence selected from the group consisting of (SEQ ID N0:1), (SEQ ID N0:2), and (SEQ ID N0:3), all shown in Figure 19, and structurally equivalent and structurally homologous sequences having at least 60% sequence identity to (SEQ ID N0:1), (SEQ ID N0:2), and (SEQ ID N0:3). The MTA/AdoHcy nucteosidase is optionally isolated from a bacterium selected from the group consisting of E. coli, S. aureus, and S. pneumoniae. The 3D structure preferably comprises a conformation selected from the group consisting of open, closed, and transition conformations. In the method, optionally:
a) the E. coli MTA/AdoHcy nucleosidase structure comprises the following amino acids:
i) adenine binding site: residues Phe151, I1e152, Ser196, Asp197, and A1a199;
ii) ribose binding site: residues GIu174, Ser76, Met9, Met173, Arg193, and Phe207;
iii) 5'-tail binding site: residues Met9, IIe50, (Va1102, Phe105, Tyr107, Pro113), Phe151, Met173, and Phe207, wherein the residues in brackets are donated from a neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Table 1;
b) the S. aur~aus MTA/AdoHcy nucleosidase structure comprises the following amino acids:
i) adenine binding site: Ser75, Phe150, I1e151, Ser195, Asp196, and A1a198;
ii) ribose binding site: MetB, Ser?5, Met172, GIu173;
iii) 5'-tail binding site: MetB, I1e49, Phe150, Met172, Phe206 and (AIa101, Phe104, Tyr106, and Pro112), wherein the residues in the brackets are from a neighbouring monomer; the amino acids arranged in an open conformation spatial relationship represented by the structural coordinates listed in Table 5; and/or c) the S. pneumoniae MTA/AdoHcy nucleosidase structure comprises the following amino acids:

i) adenine binding site: Ser76, Phe151, IIs152, Ser196, Asp197, A1a199;
ii) ribose binding site: Met9, Ser76, Met173, GIu174; and/or iii) 5'-tail binding site: Met9, IIe50, Phe151, Met173, Phe207 and (Va1102, Phe105, Tyr107, and A1a113), wherein the residues in the brackets are from a neighbouring monomer; the amino acids arranged in an open conformation spatial relationship represented by the structural coordinates listed in Table 6. Some or all of these amino acids and structural coordinates may be used.
The E. coli MTA/AdoHcy nucleosidase is optionally complexed with FMA and the amino acids are arranged in a spatial relationship represented by the structural coordinates listed in Table 2. The MTA/AdoHcy nucleosidase is optionally complexed with MTT and the amino acids are arranged in a spatial relationship represented by the structural coordinates listed in Table 3.
The MTA/AdoHcy nucleosidase is optionally complexed to AdoHcy. The MTAIAdoHcy nucleosidase structure optinally comprises the following amino acids:
i) adenine binding site: residues Phe151, t1e152, Ser196, Asp197, and A1a199;
ii) ribose binding site: residues G1u174, Ser76, Met9, Met173, Arg193, and Phe207;
andlor iii) 5'-tail binding site: residues Met9, Iie50, (Vai102, Phe105, Tyr107, Pro113,) Phe151, Met173, and Phe207, wherein the residues in brackets are donated from a neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Table 4.
The method optionally further comprises determining whether the compound interacts with the 3D structure of MTA phosphorylase or a fragment thereof and/or AdoHcy hydrolase or a fragment thereof and inhibits MTA phosphorylase or AdoHcy hydrolase activity, wherein if the compound doss not inhibit MTA phosphorylase or AdoHcy hydrolase activity, the compound is a selective inhibitor of MTA/AdoHcy nucleosidase. The fragment optionally comprises at least one of i) an active site ii) a 5' binding cavity and iii) a ribose binding site.
The MTA phosphorylase optionally comprises the following amino acids:
i) adenine binding site: residues Phe177, Ser178, Thr219, Asp220 and Asp222;
ii) 5'-methylthioribose binding site: residues Met196, Va1233, Va1236, Leu237, (His237 and Leu279), wherein the residues in brackets are donated from a neighbouring subunit;

iii) sulfatelphosphats binding site: residues Thrl8, Ar~gfiO, His61, Thr93, A1a94, and Thr197; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Protein Data Bank Accession No. 1 CG6.
The AdoHcy hydrolase optionally comprises the following amino acids i) adenine binding site: residues Leu54, Thr57, GIu59, SeMet/Met351, His353, and SeMetIMet358;
ii) ribose binding site: residues His55, G1u156, Lys186, Thr157, and Asp190 and/or iii) homocysteinyl binding site: His55, Cys79, Asn80, Asp131, Asp134, and Leu344;
the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Protein Data Bank Accession No. 1A7A.
In one aspect of the invention. the method further comprises all or part of the binding cavity of MTAIAdoHcy nucleosidase as follows:
i) the binding cavity of MTA/AdoHcy nucleosidase comprises amino acids Met9, IIe50, Va1102, Phe105, Pro113, Met173, and Phe207 and (Va1102, Phe105 and Pro113);
wherein the residues in the brackets are from a neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in one of Tables 1 to 6;
ii) the binding cavity of MTA phosphorylase comprises amino acids Va1236, Leu237, Va1233, Leu279 and His137 and (Leu279 and His137) wherein the residues in the brackets are from a neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinate listed in Protein Data Bank Accession No. 1 CG6; and iii) the binding cavity of AdoHcy hydrolase comprises amino acids His55, Cys79, Asn80, Asp131, Asp134, and Leu344; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Protein Data Bank Accession No. 1 A7A.
The method preferably further comprises: obtaining or synthesizing the compound, forming a MTA/AdoHcy nucleosidase:compound complex and analysing the complex by X-ray crystallography to determine the ability of the compound to interact with MTAIAdoHcy nucieosidase.

The method also optionally further comprises:
a) determining the three-dimensional structure of the supplemental crystal with molecular replacement analysis;
b) identifying or designing an inhibitor by performing rational drug design w~h the three-dimensional structure determined for the supplemental crystal or a fragment thereof.
The method optionally further comprises determining whether the compound inhibits MTA phosphorylase or AdoHcy hydrolase.
In one embodiment, MTA/AdoHcy nucleosidase activity is determined by:
a) incubating a test sample comprising MTAIAdoHcy nucleosidase, (ii) the compound;
and (iii) a substrate comprising 5'-methylthioadenosine or S-adenosylhomocysteine;
b) detecting substrate hydrolysis products in the test sample, wherein a change in the amount of substrate hydrolysis products in the test sample in the presence of the compound relative to in its absence indicates that the compound affects the MTA/AdoHcy nucleosidase activity.
The method optionally further comprises:
a) contacting the compound with a MTA phosphorylase or AdoHcy hydrolase; and b) measuring the activity of the MTA phosphorylase or AdoHcy hydrolase;
wherein a compound is identified for use as an inhibitor of MTA/AdoHcy nucleosidase when it inhibits MTA/AdoHcy nucleosidase and but does not change the activity of the MTA
phosphorylase or AdoHcy hydrolase.
The invention includes a compound obtained according to a method of the invention.
Another embodiment of the invention includes a computer readable medium with either (a) structural coordinate data according to at least one of Tables 1 to 6 recorded thereon, the data defining the three-dimensional structure of the MTA/AdoHcy nucleosidase, MTA/AdoHcy nucleosidase bound to an inhibitor or a fragment of the foregoing, or (b) structural data for the MTA/AdoHcy nucleosidase, MTA/AdoHcy nucleosidase bound to an inhibitor or a fragment of the foregoing recorded thereon, the structural data being derivable from the structural coordinate data of at least one of Tables 1 to 6. The structural coordinate data is optionally obtained by x-ray diffraction with a crystal of the invention.
Another embodiment of the invention includes a computer system containing either (a) structural coordinate data according to at least one of Tables 1 to 6, the data defining the 3D structure of MTA/AdoHcy nucleosidase, MTA/AdoHcy nucleosidase bound to an inhibitor or a ftagment of the foregoing, or (b) structural data for MTAIAdoHcy nucleosidase, MTA/AdoHcy nucleosidase bound to an inhibitor or a fragment of the foregoing, the structural data being derivable from the atomic coordinate data of at least one of Tables 1 to 6. The structural coordinate data is optionally obtained by x-ray diffraction with a crystal of the invention.
The invention includes a method of designing of an MTAIAdoHcy nucleosidase inhibitor through use of a crystal of the invention or structure coordinates derived therefrom. Another aspect of the invention includes a method of treating a disease in a subject, comprising administering to the subject a compound identified with a method '15 of the invention. The disease may be one caused by a microbe having MTA/AdoHcy nucleosidase.The microbe is optionally selected from the group consisting of Str~epfococcus pyrogenes, Yersinia pesfis, Vibrio cholerae, Haemophilus influenzae, Enterococcus faecalis, Helicobacter pylori, Mycobacterium tuberculosis, Staphylococcus aureus, Streptococcus pneumoniae, Carnpylobacter jejuni, ;Z0 Treponema pallidum, Borrelia burgdorferi, Salmonella typhimurium, Escherichia coli, Neisseria meningitides or Bacillus anfhracis.. The disease may be selected from the group consisting of pharyngitis, scarlet fever, impetigo cellulites, bubonic plague, pneumonic plague, cholera pneumonia urinary tract infection peptic ulcer, gastritis, tuberculosis, staphyloenterotoxicosis, staphyloenterotoxemia, meningitis, 25 pneumonia, infections campylobacteriosis, syphilis, Lyme disease, food poisoning, haemorrhagic colitis, meningitis and septicaemia.
Brief Description of the Drawings Preferred embodiments are described in relation to the drawings, in w hick:
Figure 1. Coomassie stained 15% SDS-PAGE gel showing MTA/AdoHcy 30 nuGeosidase purification. Lane 1, molecular weight markers; Lane 2, soluble lysate;
Lane 3, Ni-NTA column flow through; Lane 4, Ni-NTA column wash; Lane 5, Ni-NTA
column elution with 250mM imidazole; Lane 6, chymotrypsin cleaved MTA/AdoHcy nuGeosidase; Lane 7, MTA/AdoHcy nucleosidase after FPLC gel filtration (Superdex-75HR).

Figure 2. Amino acid sequence of the expressed MTA/AdoHcy nucleosidase enzyme. The A and B an-ows indicates the site of cleavage by chymotrypsin and the start site of the MTAIAdoHcy nucleosidase enzyme, respectively. The numbering of the protein starts at the initiating methionine, residues in the fusion are numbered from -31 to -1.
Figure 3. Crystals of E. coli MTA/AdoHcy nucleosidase (Condition 2). The crystals are approximately (0.6 x 0.2 x 0.1 mm).
Figure 4. Experimental electron density map. (a) Stereoview of a representative section of the final aA-weighted 2Fo F~ electron density map. The map is contoured at 1a and superimposed on the refined model. (b) Stereoview of the final aA-weighted 2Fo F~ electron densi!y map of the adenine molecule (ADE) in the active site.
The map is contoured at 1 a This figure was generated using Xfit [44].
Figure 5. Structure of E. coli MTAIAdoHcy nucleosidase. (a) Ribbon representation of the secondary structure elements in the MTA/AdoHcy nuGeosidase monomer: ~i-strands (red) labeled ~i1-[i10 10 are represented by an-ows and a--helices, labeled a1-a6 are represented in blue. The adenine is represented in ball-and-stick format (blue). The secondary structure was assigned using PROMOTIF [49] (~1, residues 2-7; al, 10-19; (32, 21-28; (33, 31-38; [i4, 41-47; a2, 52-66; (35, 70-79;
[36, 89-97; 3,0, 103-105; (37, 118-120; a3, 123-135; [38, 140-I47; a4, 155-164; (i9, 168-172;
a5, I7 5-184; (310, 189-198; a6, 207-229). This figure was created using Molscript [50] and Raster3D [51 ]. (b) Topology diagram of the a!(3 structure in E. coli MTAIAdoHcy nucleosidase. ~i-strands are represented as red triangles and a-helices by blue circles. Secondary structure elements are labeled as in (a) and the relative orientation of the triangle denotes the direction of the strand. In panels (a) and (b), N
and C
indicate the N- and C-termini of the molecule. This figure was generated using TOPS
[52-54]. (c) Stereoview of a Ca trace of MTAIAdoHcy nucleosidase. The structure is in the same orientation as panel (a) and every twentieth residue is labeled.
The figure was produced using the program Setor [48].
Figure 6. Structure of the E. coli MTA/AdoHcy nucleosidase and PNP dimers. (a) 3CI Ribbon representation of the E, coli MTA/AdoHcy nucleosidase dimer viewed down the non crystallographic two-fold axis. (b) Ribbon representation of the E.
coli PNP
dimer viewed down its non crystallographic 2-fold axis. Secondary structural elements within a r.m.s. deviation of 2.0 A for helices and 4.5 A for [i-sheets of the E.
coli MTA/AdoHcy nucleosidase structure are coloured in blue and red, respectively.
Adenine and formycin B are shown in each active site in a ball-and-stick format (blue) in panels (a) and (b), respectively. Figures (a) and (b) were produced using Molscript [50], and Raster3D [51 ].
Figure 7. Structural comparison of E. coli inosine-uridine N-ribohydrolase (1 MAS), the catalytic domain of human S-adenosylhomocysteine hydrolase (1A7A), human MTA phosphorylase (1CG6), E. coli PNP (1ECP) and E. coli MTAIAdoHcy nucleosidase (1JYS). For human MTAP and E. coli PNP the secondary structural elements within a r.m.s. deviation of 2.0 A for helices and 4.5 A for [i-sheets of the E.
coli MTA/AdoHcy nucleosidase structure are coloured in blue and red, respectively.
E. coli IUNH and the catalytic domain of AdoHcy hydrolase do not have structural homology to the nucleosidase and have been coloured residue-by-residue in a rainbow colour gradient, starting with the N-terminus in blue and ending at the C-terminus in red. The figures are depicted in the same orientation as in Figure 2a.
Figure 8. Structural superimposition and structure-based sequence alignment of E.
coli MTA/AdoHcy nucleosidase, human MTA phosphorylase, and E. coli PNP. (a) Structural superimposition of the Ca atoms of MTA/AdoHcy nucleosidase (yellow), MTA phosphorylase (red), and E. coli PNP (blue). The orientation is the same as in Figure 2a. The modeled MTA is coloured in light blue. This figure was made using Setor [48]. (b) Structure-based sequence alignment of E. coli MTAIAdoHcy nucleosidase (MTAN), E. coli PNP (EPNP) and human MTAP (MTAP). Secondary structural elements are labeled, with helices depicted as blue rectangles and [i-strands as red block arrows. The secondary structural elements for MTAIAdoHcy nucleosidase are as defined in the legend to Figure 5. Catalytic residues that are conserved between the three different enzymes are boxed. The figure was made using BioEdit.
Figure 9. The MTAIAdoHcy nucleosidase active site. (a) Stereoview of the adenine-binding site showing key binding residues. (b) Stereoview of the ribose-binding site showing key binding residues. In both panels, the modeled MTA
substrate is coloured in yellow and the adenine ring is in purple. Water molecules involved in catalysis are represented as light blue spheres. Figures (a) and {b) were generated using VMD [55]. (c) Schematic representation of the MTA/AdoHcy nucleosidase active site. Dotted lines represent protein-protein or protein-ligand hydrogen bonds, distances in angstroms are shown above the dotted tines. Residues donated to the active site from the neighbouring monomer are denoted with an asterix. The diagram was produced using CHEMDRAW (CambridgeSoft, Cambridge, MA).

Figure 10. Structures of MTA, Formycin A (FMA) and 5'-methylthiotubercidin (MTT).
Although all three structures have different IUPAC numbering schemes, for ease of comparison MTT and FMA will be labeled in a similar scheme to MTA.
Figure 11. E. colt MTA/AdoHcy nucleosidase transition state inhibitor complexes. (a) Ribbon diagram of the overall structure of the monomer. (b) Ribbon diagram of the overall dimer viewed down the non-crystallographic two fold axis. The ribbon diagrams were generated using Swiss-PDB Viewer and POV-RAY. (c) The final E.
coli MTA/AdoHcy nucleosidase aA-weighted 3a ~Fo~-~Fc~ electron density map superimposed with the refined model in the active site. The electron density maps were created using Xfit .
Figure 12. Active site of MTAlAdoHcy nucleosidase complexed with MTT. Ball and stick representation of the (a) adenine and the (b) ribose and 5' tail binding sites.
Residues coloured in gn3en are donated from the neighbouring subunit. (c) Stereo van der Waals surface representation of the active site with bound MTT. Acidic residues are coloured in red and basic residues are depicted in blue. (d) A
schematic representation of the interactions between the transition state analogs and the enzyme. Dotted lines represent protein-protein or protein-ligand hydrogen bonds and distances in angstroms (A) are shown above the dotted lines. Residues donated from a neighbouring subunit are shown in shaded boxes. The ball and stick and the 2 0 molecular surface diagram were generated using VMD.
Figure 13. Active site of MTAIAdoHcy nuclsosidase complexed with FMA. Ball and stick representation of the (a) adenine and the (b) ribose and 5' tail binding sites.
Residues coloured in green are donated from the neighbouring subunit. These figures were produced using VMD . (c) A schematic representation of the interactions :?5 between FMA and the enzyme. This panel is labeled as shown in Figure 12.
Figure 14. Conformations of the MTA, MTT, and Formycin A nucleosides in the active site. The transition state inhibitors MTT (red), and FMA (green) in the inhibitor bound structures were superimposed with MTA (blue) from human MTA phosphorylase (PDB code: 1CG6) . The figure was generated using VMD.
30 Figure 15. Root mean square deviation (RMSD) plots of Ca posi~ons.
Structural differences between monomer A of the adenine and MTT-bound structure (blue) and FMA and MTT-bound structure (red). The generation of the superimposition of the structures is described in the Experimental Procedures section. Residues 202-were disordered in the adenine-bound crystal and thus the rmsd values for these residues are shown to be zero. a-helices and ~i-sheets are labeled as defined in Lee et al and are shown as rectangles and arrows, respectively.
Figure 16. Intrasubunit conformational changes upon transition state analog binding.
(a) Ribbon diagram of the superimposed adenine (yellow) and MTT (purple) 5. complexed MTA/AdoHcy nucleosidase monomers. (b) Ribbon diagram of the a6 helix extension. (c) Ribbon diagram of the 150's loop shift. (d) Ribbon diagram of the helix a1 shift. Figures were produced using Swiss-PDB Viewer and POV-RAY.
Figure 17. Intersubunit conformational changes upon transition state analog binding.
(a) Ribbon diagram of the superimposed adenine and MT'T complexed dimers. The dimers are superimposed as described in the Experimental Procedures section and are coloured blue and green, respectively. (b) A closer view of the 100's loop involved in donating residues into the neighbouring subunit. This figure was generated using Swiss-PDB Viewer and POV-RAY.
Figure 18. Proton relay mechanism of MTAIAdoHcy nucleosidase. Dotted lines 1;i represent protein-protein or protein-ligand hydrogen bonds and distances in angstroms (A) are shown above the dotted lines. Potential hydrogen bonds are shown as red dashed fines. This figure was generated using VMD.
Figure 19. Alignment of amiro acid sequences of MTA/AdoHcy nucleosidase from E.
coli (SEQ ID N0:1), S. aureus (SEQ ID N0:3) and S. pneumoniae (SEQ ID N0:3).
Also 2~0 shown are M. influenzae (SEQ ID N0:6), S. Typhimurium (SEQ ID N0:7), H.
pylori (SEQ ID N0:8), M. tuberculosis (SEQ ID NO:9), T. pallidum {SEQ ID N0:10) 2;5 Figure 20. (a) Amino acid sequences for human AdoHcy hydrolase (SEQ ID N0:4;
accession code # NP 000678), and (b) amino acid sequence for human MTA
phosphorylase (SEQ ID N0:5; accession code # Q13126).
Detaiisd Description of the Invention In one aspect the invention is directed to the three-dimensional structure of an isolated and purified enzyme MTA/AdoHcy nucleosidase and its structure coordinates.
These structures have been obtained from E. coli, S. aureus and S. pneumoniae. The 30 structures are very similar and may be generalized to other MTA/AdoHcy nucleosidases. The sequence alignments of different nucleosidase species in Fig. 19 reveal the conservation of key active site residues. The active site is highly conserved between the various species of MTAIAdoHcy nucleosidase.
The structure of E. coli MTA/AdoHcy nucleosidase has been determined complexed to adenine, and the transition state inhbitors, MTT and FMA. The structure of a mutant E12A MTA/AdoHcy nuclsosidase has also been determined bound to one of its natural substrates, Adol-by. These structures show critical regpns, such as the active site, and provide a general model for MTA/AdoHcy nucleosidase actNity. Structural coordinates for the nucleosidases are provided in tables, as described below .
Table 1 Adenine-bound E. coli MTAIAdoHcy nucleosidase Table 2 FMA-bound E. coli MTAIAdoHcy nucleosidase Table 3 MTT-bound E. coli MTA/AdoHcy nucleosidase Table 4 E12A AdoHcy-bound MTA/AdoHcy nucleosidase Table Formycin A-bound S. aureus MTA/AdoHcy nucleosidase Table 6 8-aminoaderine-bound S. pneunoniae MTAIAdoHcy nucleosidase The invention also includes methods of identifying compounds capable of inhibiting the enzymes. The inhbitors are preferably selective for bac9srial MTA/Adol-~y nucleosidases in that they do not affect mammalian MTA phosphorylase or Adol-Ey hydrolase activity. These selective inhbitors are useful for treating d~eases caused by baciaria that have MTAIAdoHcy nucleosidases.

h preferred examples, the 3D structure of the MTA/Adol-Ey nucleosidase is the E. coli, S. aureus or S. pneunoniae MTA/AdoHcy nucleosidase enzyme (amino acid sequences are shown in Figure 19). The structures are very similar and may be generalized to other MTA/AdoHcy nucleosidases. An example of the sequence identity between nucleosidases is provided below.
Organism Identity (compared to E. coli) Similarity S. pneumoniae 0.41 0.70 S. aureus 0.53 0.75 H. influenzae 0.56 0.78 The "3D structure" of MTA/AdoHcy nuclaosidase includes the structure of the MTA/AdoHcy nucleosidase domains fitted together. Another aspect of the invention is to use the structural coordinates of the MTA/AdoHcy nucleosidase to reveal the atomic details of the active site and other domains of MTA/AdoHcy nucleosidase. The entire enzyme may be used or particular regions of interest may be used. Prior to this invention, the 3D structure of the enzyme and its mechanism of activity were unknown. The relative positions of amino acids which bound MTA/AdoHcy nuclsosidase and provided enzyme activity were also poorly understood. The invention details the atomic interactions of substrate and inhbitors w ith the MTA/AdoHcy nucleosidase. Furthermore, a mechanism is detailed w hich shows how this substrate bincing results in conformational charges of the MTAIAdoHcy nucleosidase.
Structural and conformational changes induced in the enzyme may also be studied now that the 3D structure has been solved.
Another aspect of the invention is to use the structural coordinates of either the E.
colt, S. aurreus, or S. pneumoniae MTA/AdoHcy nucleosidase to homology model other nucleosidase species.
This invention provides the first rational drug design strategy for modulating enzyme activity. The structure coordinates and atomic details of MTA/AdoHcy nucleosidases are useful to design, evaluate (preferably computationally) and synthesize inhibitors of MTA/AdoHcy nucleosidase that prevent or treat bacterial pathologies. The invention includes methods for identifying compounds that can interact with MTA/AdoHcy nucleosidase. The method for idertifying inhbitors preferably include fitting structures of MTA/AdoHcy nucleosidase domains into the 3D structure of the complete inhbitor bound MTA/AdoHcy nucleosidase. These interactions can be easily identified by comparing the structural, chemical and spatial characteristics of a candidate compound to the three dimensional stnrcture of the MTA/AdoHcy nucleosidase.
Sinae the amino acids that are responsible for enzyme activity and binding were identfied by this invention, drug design may be done on a rational basis.
The structure serves as a detailed bas's for the desgn and testing of inhbitors, ini~aNy in the computer, but also in vitro in cell cuilure and in vivo, providing a method for identifying inhbitors hav~g speafic contacts w ith the MTA/AdoHcy nucleosidase or an isoform, homologue or mutant. The effect of a modification to a substrate or inhibitor such as M1T or FMA may be readily viewed on a computer, without the need to synthesize the compound and assay it in vitro. As well, non-protein organic molecules may also be compared to the MTA/AdoHcy nucleosidase on a computer.
One can readily determine if the molecules have suitable structural and chemical characteristics to interact with, and activate or inhibit, enzyme activity.
The invention includes the enzyme modulators discovered using all or part of an enzyme structure of the invention (preferably the 3D structure) and the methods of the invention.

Crystals Crystal Properties The invention includes a crystal comprising MTAIAdoHcy nudeosidase that is suitable for x-ray crystallographic analysis. The crystal preferably includes nucleosidase from E. coli, S. aureus or S. pneumoniae. The crystal including E. coli MTA/AdoHcy nucleosidase optionally comprises all or part of the amino acid sequence shown in Figure 19 (SEQ ID N0:1) or a structurally equivalent or structurally homologous sequence having at least 60°~ sequence identity to all or part of (SEQ
ID N0:1);
The crystal including S. aur~eus MTA/AdoHcy nucleosidase optionally comprises all or part of the amino acid sequence shown in Figure 19 (SEQ ID N0:2) or a structurally equivalent or structurally homologous sequence having at least 60% sequence identity to all or part of (SEQ ID N0:2). The crystal including S. pneumoniae MTA/AdoHcy nucleosidase optionally comprises ail or part of the amino acid sequence shown in Figure 19 (SEQ ID N0:3) or a structurally equivalent or structurally homologous sequence having at least 50% or 60% sequence identity to all or part of (SEQ ID N0:3). One may also use polypeptides which have sequence identity at least about: >70°r6, >80% or >90% more preferably at least about >95%, >99% or >99.5% Identity is calculated according to methods known in the art.
Sequence identity is most preferably assessed by the BLAST version 2.1 program advanced search (parameters as above). BLAST is a series of programs that are available online at http:/Mrww.ncbi.nlm.nih.gov/BLAST. The advanced blast search (http://www.ncbi.nlm.nih.gov/blastlblast.cgi?Jform=1) is set to default parameters. (ie Matrix BLOSUM62; Gap existence cost 11; Per residue gap cost 1; Lambda ratio 0.85 default). References to BLAST searches include: Altschul, S.F., Gish, W., Miller, W., Myers, E.W. 8 Lipman, D.J. (1990) "Basic local alignment search tool." J. Mol.
Biol.
215:403 410; Gish, W. & States, D.J. (1993) "identification of protein coding regions by database similarity search." Nature Genet. 3:266_272; Madden, T.L., Tatusov, R.L.
& Zhang, J. (1996) "Applications of network BLAST server" Meth. Enzymol.
266:131 141; Altschul, S.F., Madden, T.L., Sch~ffer, A.A., Zhang, J., Zhang, Z., Miller, W. & Lipman, D.J. (1997) "Gapped BLAST and PSI BLAST: a new generation of protein database search programs." Nucleic Acids Res. 25:3389 3402; Zhang, J.
&
Madden, T.L. (1997) "PowerBLAST: A new network BLAST application for interactive or automated sequence analysis and annotation." Genome Res. 7:649 656. The invention includes the use of polypeptides with mutations that cause an amino acid change in a portion of the polypeptide not involved in providing activity or an amino acid change in a portion of the polypeptide involved in providing activity so that the mutation increases or decreases the activity of the polypeptide. At least one methionine in SE(~ ID NOS:1-3 may comprise selenomethionine.. Using these crystals, the three-dimensional structure of MTA/AdoHcy nucleosidase was solved using high resolution x-ray crystallography. It will be readily apparent that one could use a variant of the nucleosidase with an amino acid sequence that differs from SEQ
ID
NOS:1-3 by having conservative or non-conservative substitutions. For example, an acidic amino acid may be replaced with another acidic amino acid. Amino acids may be categorized as follows: Acidc amino acids: Asp Glu; hydrophiic armo acids:
Asn, Gln, Ser, Thr, Tyr; hydrophobic amino acids acids: Ala, Cars, Phe, Met, Trp, Leu, Vie, Val, Pro, Gly; basic amino adds: Lys, His, Arg. Non-conservative substitutions may also be made although preferably they will nd sign~icantty affect the 3D structure of the nucleosidase. The sequence may have other changes such as a selenomethionine in place of a methionine. The sequence will also often include at least one amino acid of a 6-His tag linker sequence (the His tag being useful in protein purification) connected to the N- or C-terminus of the MTA/AdoHcy nucleosidase. As well, residual compounds such as adenine may bind to the nucleosidase. The invention indudes sequences and 3Dstructures having arrino acid changes that do nd sign~icanby alter the 3D nucleosidase structures disclosed herein and w hich are still su~able for rational drug design The properties of the crystals are described in more detail in the examples below and in the attached tables. The invention includes the use of a crystal of the invention or structure coordinates derived therefrom for drug design of a MTA/AdoHcy nucleosidase inhibitor for treatment of a microbial disease, preferably bacterial disease, caused by, for example, a bacteria or microbe such as: Streptococcus pyrogenes, Yersinia pestis, Vibrio cholerae, Haemophilus intluenzae, Enterococcus faecalis, Helicobacter pylori, Mycobacterium tuberculosis, Staphylococcus aureus, Streptococcus pneumoniae, Campylobacter jejuni, Treponema pallidum, Borrelia burgdon'eri, Salmonella typhimurium, Escherichia coli, Neisseria meningitides or Bacillus anthracis and any microbe, preferably bacteria, having MTA/AdoHcy nucleosidase. The methods of using the crystal involve subjecting the crystal to x-ray diffraction and obtaining structure coordinates from the crystal. The coordinates are then used in drug design as described in this application. In one embodiment, the crystal including the MTAIAdoHcy nucleosidase is in an open conformation and optionally comprises bound adenine or 8-aminoadenine. The open conformation refers to the nucleosidase in a free state or bound to a compound that does not significantly alter the nucleosidase conformation. The E. coli MTA/AdoHcy nucleosidase structure comprises the diffraction properties presented in Table 7 and the structural coordinates presented in Table 1. The S. aureus MTAIAdoHcy nucleosidase structure comprises the diffraction properties presented in Table 10 and the structural coordinates presented in Table 5. The S, pneumoniae MTAIAdoHcy nucleosidase stnrcture comprises the diffraction properties presented in Table 10 and the structural coordinates presented in Table 6. In the crystal, the E. coli MTAIAdoHcy nucleosidase may have approximately the following physical characteristics:
diffracting to a minimum d spacing of about 1.9 A; a density determined by a Matthews coefficient of about Vm = 2.4 A3/Da; and a solvent content of about 48%.
The S. aureus MTAIAdoHcy nucleosidase may have approximately the following physical characteristics: diffracting to a minimum d-spacing of about 1.9 A; a density determined by a Matthews coefficient of about Vm = 2.2 A~IDa and a solvent content of about 43%. The S. pneumoniae MTA/AdoHcy nucleosidase may have approximately the following physical characteristics: diffracting to a minimum d spacing of about 1.6 A; a density determined by a Matthews coefficient of about Vm = 2.6 A3IDa and a solvent content of about 52°i6.
The E. coli MTA/AdoHcy nuGeosidase may comprise a space group P2,2,2 and a unit cell having dimensions a = 50.92A, b = 133.99A, c = 70.88A, o~(i--ry=90°. The S.
aureus MTAIAdoHcy nucleosidase may comprise a space group P2,2,2 and a unit cell having dimensions with a unit cell a=58.3 A, b=81.7 A, and c=45.5 A, ar.~3=y==90°.
The S. pneumoniae MTA/AdoHcy nucleosidase may comprise a space group 14132 and a unit cell having dimensions a=145.7 A, b=145.7 A, and c=145.7 A, o~~--~
90°.
Typically, the nucleosidase will have one or two monomers per asymmetric unit.
In the crystal, a) the E. coli MTA/AdoHcy nucleosidase structure preferably comprises the following 2.5 amino acids:
i) adenine binding site: residues Phe151, I1e152, Ser196, Asp197, and A1a199;
ii) ribose binding site: residues GIu174, Ser76, Met9, Met173, Arg193, and Phe207;
iii) 5'-tail binding site: residues Met9, IIe50, (Va1102, Phe105, Pro113), Phe151, Met173, and Phe207; wherein the residues in the brackets are from the neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Table 1 b) the S. auneus MTA/AdoHcy nucleosidase structure comprises the following amino acids:
i) adenine binding site: Ser75, Phe150, I1e151, Ser195, Asp196, and A1a198;

ii) ribose binding site: MetB, Ser75, Met172, GIu173;
iii) 5'-tail binding site: MetB, I1e49, Phe150, Met172, Phe206 and (AIa101, Phe104, Tyr106, and Pro112), wherein the residues in the brackets are from the neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Table 5; and/or c) the S. pneumoniae MTA/AdoHcy nucleosidase structure comprises the following amino acids:
adenine binding site: Ser76, Phe151, I1e152, Ser196, Asp197, A1a199;
ii) ribose binding site: Met9, Ser76, Met173, GIu174;
iii) 5'-tail binding site: Met9, IIe50, Phe151, Met173, Phe207 and (Va1102, Phe105, Tyr107, and A1a113), wherein the residues in the brackets are from the neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Table 6.
The MTA/AdoHcy nucleosidase preferably comprises a dimer in which each monomer includes a mixed a/~i domain comprising a nine-stranded mixed ~3-sheet, proximate to six a-helices and a 3,o helix.
MTAIAdoHcy nucleosidase has also been crystallized with its substrate and the inhibitors MTT and FMA. Accordingly, in another embodiment, the MTA/AdoHcy nucleosidase is in a transition conformation and complexed to an inhibitor.
The transition conformation refers to the nucleosidase conformation when bound to a transition state analog or inhibitor, such that the analog or inhibitor causes the nucleosidase conformation shifts to its transition state conformation. In one variation, the MTA/AdoHcy nucleosidase comprises an E. coli MTA/AdoHcy nucleosidase. The inhibitor optionally comprises FMA or MTT. The diffraction properties for these crystals are presented in Tables 2 and 3. In this embodiment, the crystal may have a space group P2,2,2,. The FMA-bound nucleosidase crystal may have a unit cell having dimensions a=51.1 A, b=69.7 A, c=127.8 A, a=~i-='y=90°. When the inhibitor is MTT, the crystal may comprise a unit cell having dimensions a=51.3 A, b=69.3 A, c=127.2 A, a=(3=~=90°.
When the inhibitor is FMA, the E. coli MTA/AdoHcy nucleosidase structure may comprise the diffraction properties presented in Table 10 and the structural coordinates presented in Table 2.
When the inhibitor is FMA, the E. coli MTA/AdoHcy nucieosidase structure optionally comprises the following amino acids:

i) adenine binding site: residues Phe151, I1e152, Ser196, Asp197, and Aia199;
ii) ribose binding site: residues GIu174, Ser76, Met9, Met173, Arg193, and Phe207;
andlor iii) 5'-tail binding site: residues Met9, IIe50, (Va1102, Phe105, Pro113), Phe151, Met173, and Phe207, wherein the amino acids in the brackets are from the neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Table 2.
UVhen the inhibitor is MTT, the E. coli MTA/AdoHcy nucleosidase s~vcture may comprise the following amino acids:
i) adenine binding site: residues Phe151, I1e152, Ser196, Asp197, and A1a199;
ii) ribose binding site:residues GIu174, Ser76, Met9, Met173, Arg193, and Phe207; or iii) 5=tail binding site: residues Met9, IIe50, (Va1102, Phe105, Tyr107, Pro113), Phe151, Met173, and Phe207; wherein the residues in the brackets are from the neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Table 3.
In this embodiment, the MTA/AdoHcy nucleosidase preferably comprises a subunit including a central nine-stranded mixed ~i-sheet and a five ~3-stranded sheet proximate to six a-helices and a 3,o helix.
In another embodiment, the E. coli MTAIAdoHcy nucleosidase is in a closed conformation and complexed to a substrate. The closed conformation is an conformation between the open conformation and the transition conformation.
The bound substrate causes conformational changes in the nucleosidase.
The MTA/AdoHcy nucleosidase crystal may comprise an E. coli MTA/AdoHcy nucleosidase.
In one variation, glutamate 12 in the active site of the E. coli MTAIAdoHcy nucleosidase sequence has been converted to alanine or another neutral amino acid.
The crystal may comprise a space group P2,2,2, and a unit cell having dimensions a=
52.0 A, b= 69.0 A, c= 128.1 A, a=~i=y=90°.
In this variation, the E. coli MTA/AdoHcy nudeosidase structure optionally comprises 3U the structural coordinates presented in Table 4. The E. coli MTA/AdoHcy nucleosidase structure preferably comprises the following amino acids:
i) adenine binding site: residues Phe151, I1e152, Ser196, Asp197, and A1a199;

ii) ribose binding site: residues GIu174, Ser76, Met9, Met173, Arg193, and Phe207;
and/or iii) 5'-tail binding site: residues Met9, IIe50, (Va1102, Phe105, Tyr107, Pro113), Phe151, Met173, and Phe207, wherein the residues in the brackets are from the neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Table 4.
The MTAIAdoHcy nucleosidase preferably comprises a subunit including a central nine-stranded mixed oc/[i-sheet and a five [i-stranded sheet proximate to six a-helices and a 3,o helix.
The pathogenic species, S. aureus and S. pneumoniae MTAIAdoHcy nucleosidase were crystallized with Formycin A and 8-aminoadenosine, respectively.
Crystallization Procedure To prepare crystals, the proteins were first screened using commercial sparse matrix screens such as those from Hampton Research yhtta:llwww.hamptonresearch.com) and Emerald Biostructures (htt~:Ilwww.~meraldbio~tructur~s.com). The preferred screens are Hampton I and II, Wizard I and II, and Cryo I and II. Screens are visualized for crystals under a light microscope. Conditions are optimized to obtain crystals for x-ray diffraction.
In one example, purified E. coli MTA/AdoHcy nucleosidase, may be crystallized, for example, by hanging drop vapour diffusion in a solution comprising buffer and precipitating solution. Alternative crystallization techniques such as sitting drop vapour diffusion could also be used according to techniques known in the art.
Another aspect of the invention relates to a method for crystallizing a MTA/AdoHcy nucleosidase, comprising crystallizing MTAIAdoHcy nucleosidase on a substrate by hanging drop vapour diffusion in a solution comprising buffer and precipitating solution. The substrate optionally comprises a siliconized coverslide, a plastic coverslide and a plastic microbridge. The solution optionally comprises about:
0.6-1.0 M sodium citrate, 100 mM 2-(N-cyclohexylamino)ethanesulfonic acid (CHES) pH
8.5-9.5 and 0-0.8 mM 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate (CHAPS) detergent. The MTAIAdoHcy nucleosidase is optionally at a concentration of about: 10 - 20 mg/mL, preferably 15 mglmL. The crystals are preferably grown to a size of at least 0.1 x 0.1 x 0.1 rnm, more preferably 0.2 mm x 0.1 mm x 0.1 mm to 0.7 x 0.4 x 0.3 mm. The method preferably further comprises comprising contacting the crystals with a cryoprotectant for a time period sufficient to infuse the crystals with cryoprotectant without cracking the crystal, preferably about 2 minutes.
The step of contacting the crystals with a cryoprotectant optionally comprises:
a) contacting the crystals with about: 15% (wlv) glucose, 0.7M-0.9M sodium citrate, 100 mM CHES pH 8.5; and b) contacting the crystals with about: 30% wN glucose, 0.7 M-0.9M sodium citrate, 100 mM CHES pH 8.5.
In another aspect, the invention includes a method for crystallizing a MTA/AdoHcy nucleosidase in complex with an inhibitor, comprising: a) contacting the MTAIAdoHcy nucleosidase with an inhibitor and b) crystallizing MTA/AdoHcy nucleosidase on a substrate suitable for crystallization by hanging drop vapour diffusion in a solution comprising buffer and precipitating solution. In the method, the MTA/AdoHcy nucleosidase is optionally in a concentratian of about: 15 mg/ml and is contacted with about 1 mM of inhibitor. The substrate optionally comprises a siliconized coverslide.
The solution optionally comprises about: 35-60% (w/v) PEG 200, 100 mM sodium acetate pH 4.0- pH 5.5, 100 mM NaCI, and 0-10 mM cobaltous chloride. The crystals are preferably are grown to a size of at least: 0.05 mm x 0.05 mm x 0.2 mm , preferably0.05mmx0.05mmx1.5mmto0.15mmx0.15mmx1.Omm.
In another variation, the invention relates to a process for determining whether a candidate compound binds to MTA/AdoHcy nucleosidase, comprising, a) exposing the MTA/AdoHcy nucleosidase to the candidate compound before or after MTA/AdoHcy nucleosidase crystallization;
b) obtaining an X-ray diffraction pattern of the MTAIAdoHcy nucleosidase with exposure to the candidate compound; and c) determining whether a candidate compound:MTAIAdoHcy nucleosidase complex is formed by comparing the X-ray diffraction pattern of the MTA/AdoHcy nucleosidase when exposed to the candidate compound to the X-ray diffraction pattern of the MTA/AdoHcy nucleosidase obtained when not exposed to the candidate compound.
Structural Coordinates of Crystallized Amino Acids Each of the constituent amino acids of the nucleosidase is defined by a set of structure coordinates (also called structural coordinates). The term "structure coordinates" refers to Cartesian coordinates derived from mathematical equations related to the patterns obtained on diffraction of a manochromatic beam of x-rays by the atoms (scattering centers) of a nucleosidase or nucleosidase complex in crystal form. The diffraction data are used to calculate an electron density map of the repeating unit of the crystal. The electron density maps are then used to establish the positions of the individual atoms of the nucleosidase or complex.
Slight variations in structure coordinates can be generated by mathematically manipulating the nucleosidase structure coordinates. For example, the structure coordinates set forth in this application could be manipulated by crystallographic permutations of the structure coordinates, fractionalization of the structure coordinates, integer additions or subtractions to sets of the structure coordinates, inversion of the structure coordinates or any combination of the above. Alternatively, modifications in the crystal structure due to mutations, additions, substitutions, and/or deletions of amino acids, or other changes in any of the components that make up the crystal, could also yield variations in structure coordinates. Such slight variations in the individual coordinates will have little effect on overall shape. If such variations are within an acceptable standard error as compared to the original coordinates, the resulting three-dimensional shape is considered to be structurally equivalent. Structural equivalence is described in more detail below.
It should be noted that slight variations in individual structure coordinates of the nucleosidase or its complexes, as defined above, would not be expected to significantly alter the nature of chemical entities inhibitors that could associate with the active site (also called complexing or binding). In this context, the phrase "associate with"
refers to a condition of proximity between a chemical entity, or portions thereof, and a nucleosidase or portions thereof. The association may be non-covalent, wherein the juxtaposition is energetically favored by hydrogen bonding, van der Waals forces, or electrostatic interactions, or it may be covalent. Thus, for example, a compound that bound to or interfered with the active site of a nucleosidase would also be expected to bind to or interfere with another active site whose structure coordinates define a shape that falls within the acceptable error.
It will be readily apparent to those of skill in the art that the numbering of amino acids in other nucleosidase may be different than that of a nucleosidase disclosed in this application.
MTAIAdoHcy Nuclmosidase Structures These structures described below have been obtained from E. coli, S. aureus and S.
pneumoniae. The structures are very similar between these three species and are optionally generalized to other MTA/AdoHcy nucieosidases. The sequence alignments of different nucleosidase species in Fig. 19 reveal the conservation of key active site residues. The active site is highly conserved between the various species of MTA/AdoHcy nucleosidase. For example, the adenine-binding site and ribose-binding site are conserved. The catalytic acid (Asp197) and catalytic base (GIu12) are also conserved. The hydrophobic pocket is conserved. The nucleophilic water binding site primarily contains conserved residues with a few residues having conservative substitutions. Residues conserved are: AlaB, GIu12, GIy75, G1u172, GIu174, and Arg193.
Residues with conservative substitutions are: Met9, and Ser76 (the residues quoted are from the E. coli nucleosidase). Thus, the methods and crystals described in this application with E. coli, S. aureus and S. pneumoniae are readily extended to include any MTA/AdoHcy nucieosidase, such as those listed in Figure 19.
Structure determination Adenine-bound nucleosidase- The E. coli MTAIAdoHcy nucleosidase was expressed and purified. The crystallized protein preferably consists of 232 protein residues and a 10 amino acid N-terminal extension. This N-terminal extension is part of the 31 amino acid 6-histidine containing tag used for purification of the protein.
Chymotrypsin treatment of the protein cleaves the first 21 residues of the 31 residue tag. The structure of the selenomethionyl-incorporated protein was determined at 2.4 A resolution using the multiwavelength anomalous diffraction (MAD) technique (see Material and Methods; Table 8). The resulting model was refined against a high-resolution 1.90 A data set measured on a native sulfur containing crystal to a R~,St =
0.215 and R~" = 0.237 (Table 9}. The final model consists of residues 1-201 and 206-230. The N-terminal tag (residues -10 to -1) and residues 202-205 and 231-232 are not present in the final model because of weak or missing electron density.
FMA and MTT bound nucieosidase- The FMA and MTT-bound structures were solved with molecular replacement using the program CNS. The adenine-bound 25~ nucleosidase structure was used as the search model (see Material and Methods). In the MTT and FMA nucleosidase structures, a dimer is present in the asymmetric unit.
In both structures all 232 residues of the protein were clearly visible in the electron density map and have been modeled. The FMA and MTT complexed structures were refined to a R~ = 20.2 % and R~ = 24.2 °A, and R~,at =18.3 % and R~ =
21.9 %, respectively (Table 10). Analysis of the structures in PROCHECK and WHATIF
reveal that none of the nonglycine residues fall into the disallowed region of the Ramachandran plot.

Overall structure of the molecule Adenine-bound structure- The MTA/AdoHcy nucleosidase molecule is a single mixed a!(i domain with overall dimensions of ~50 x 40 x 35 A (Figure 5a-c). The central portion of the molecule is made up of a large twisting nine-stranded mixed ~3-sheet, with strands labeled ail, ~2, [33, (34, (35, (36, [38, (39 and X10. 0. Six a-helices and a small 3,a helix flank and pack into the ~i-sheet grooves. Although the enzyme has a nucleoside-binding site, MTA/AdoHcy nucleosidase does not contain the classical ~ia(3a[3 Rossmann fold (19].
FMA and MTT bound structures- The overall topology of the MTT and FMA
nucleosidase complexes is similar to that previously published. Each subunit has the same structure as the adenine bound form of the nucleosidase (Figure 11 ). The root mean square deviation (RMSD) for monomers A and B in the FMA and M'tT-bound structures are 0.20 A and 0.22 A, respectively. Strong electron density was seen in both active sites of the MTA/AdoHcy nucleosidase structures throughout refinement.
This electron density was easily recognizable as either FMA or MTT (Figure 11 c).
Each active site is fully occupied with one bound inhibitor.
Quaternary structure In the E. coli MTA/AdoHcy nucleosidase crystal structure, two monomers related by 2-fold non-crystallographic symmetry ar9e found in the asymmetric unit (Figure 6a, +
2.0 11 b). The interface of the two monomers is highly hydrophobic. The subunit interface involves a-helices a2 and a5, , the short 3,o helix and two other loops. The residues involved at the interface are GIy29, IIe50, GIy51, Lys52, Va153, AIa100, Asp101, Va1102, AIa104, Phe105, Leu112, Asp149, AIa150, Phe151, Met173, Va1181, Phe185 and one face of helix a2 (Leu57, Leu61). The 16 non-polar residues interact via sidechain-sidechain hydrophobic interactions, while the 3 polar residues are involved in mainchain-mainchain and sidechain-sidechain hydrogen bond interactions.
The amide nitrogen and carbonyl oxygen of Asp101 is hydrogen bonded to the carbonyl oxygen of Asp149 and the amide nitrogen of Phe151, respectively.
Lys52 N_ makes an electrostatic interaction with O 2 of Asp149. Upon dimerization, ~13%
or 1300 A2 of the monomer surface is buried in the dimer interface.
While the presence of two E. coli MTAIAdoHcy nucleosidase molecules in the crystallographic asymmetric unit is not necessarily proof that the protein exists as a dimer in solution, the observation that the protein elutes from an analytical gel filtration column (FPLC-Superdex-75 HR) at a volume consistent with a dimer of 51 kDa (data not shown) and the extensive hydrophobic nature of the monomer-monomer interactions proves this hypothesis. In addition, the MTT and FMA bound nucleosidase structures revealed that a number of residues from the neighbouring subunit contribute to substrate binding. Residues Va1102, Phe105, and Pro113 form part of a 3~o helix and loop that create a hydrophobic pocket into which the 5 =tail of the ribose appears to bind. Taken together these data show that E. coli MTAIAdoHcy nucleosidase is functional as a dimer in solution Sfrucfural homologies Prior to the structure determination of MTAIAdoHcy nucfeosidase, we had speculated (20] that it may share structural homology with the catalytic domain of AdoHcy hydrolase [21] and inosine-uridine nucleoside N-ribohydrolase (IUNH) [22].
AdoHcy hydrolase shares a common substrate with MTAIAdoHcy nucleosidase while ~JN-I
performs a similar reaction, hydrolyzing the N-ribosidic bond of purine ribosides to form purine and ribose. No structural similarities are found when the central (3-strands of MTA/AdoHcy nucleosidase are superimposed onto the core parallel a/[3 structures (topology: -1 x, -1 x, 3x, 1 x, 1 x, 2, -1 ) of the catalytic domains of AdoHcy hydrolase and IUNH (Figure 7). The topology of the core 9-element [i-sheet in MTA/AdoHcy nucleosidase is (-3x, +1, +1, +2x, +3, -1, +2, -1 x, -2x).
E. coli MTAIAdoHcy nucleosidase shows striking structural similarity to two different classes of purine nucleoside phosphorylase (PNP) (Figure 7 and 8). PNPs can be classified in two main categories: (a) low molecular mass (~90 kDa) homotrimers and (b) high molecular mass 0110-115 kDa) homohexamers. The low molecular weight trimeric class of PNPs is found in all mamma~an systems and many microbes. h general, the enzymes in this class are specific for 6-oxopurines, inosine and guanosine. However MTA phosphorylase is an exception, as this trimeric enzyme is highly specific for 6-aminopurines [23, 24]. Structures of four trimeric PNPs have been solved: bovine spleen PNP [25], human erythrocyte PNP [17], Cellulomonas sp.
PNP [26] and human MTA phosphorylase (MTAP) [27]. For the purpose of our comparison, we have chosen MTAP as the representative member of the trimeric class of PNPs since this enzyme, like the nucleosidase, binds MTA. The high molecular weight class of PNPs is found in E. coli and many microorganisms.
The enzymes in this class cleave both 6-amino (adenosine) and 6-oxopurines (inosine/guanosine) [28]. E, coli PAP [29] is the only member of the °high molecular weight class of PNP whose structure has been determined.

Pairwise superimposition of MTAP and E. coil PNP with MTA/AdoHcy nucleosidase yields r.m.s. deviations of 1.47 A for 161 and 1.57 ~4 for 156 Ca positions, respectively, indicating that the overall structure of the three proteins is essentially the same (Figure 7 + 8). The active sites of all the enzymes are found in a similar locale.
An analysis of the secondary structure composition revealed that E. coil MTA/AdoHcy nucleosidase contains significantly more secondary structural elements than the two classes of PNPs (Figure 8). Overall, the E. coil nucleosidase has 5%
more secondary structural elements than the hexameric phosphorylases and over 10% more than the mammalian phosphorylases. The PNPs have a larger percentage of loops, which are involved predominantly in subunit-subunit interactions.
Interestingly, hexameric E. coil Pfd' is arranged as a trimer of dimers. The dimer interface of E. coil PNP is primarily hydrophobic with a small number of electrostatic interactions between sidechains [29, 30], similar to that seen in the nucleosidase. A
closer inspection of the secondary structural elements involved in subunit-subunit interactions reveals significant differences between the two structures (Figure 6). h E. coil PNP, dimerization involves three loops and parts of 2 helices (a3, and a4) [29, 30], with the interactions made predominantly between a helix-loop or two loops. h the nucleosidase, the contacts between subunits are more extensive than in E.
toll PNP and dimerization primarily involves helix-loop (ie. a2 to 3,°-[i7, and a2 to ~8-a4) or helix-helix interactions (between a2-a2 and a2-a5). The dimer interfaces and relative location of the active sites in the dimer are not conserved between the two enzymes (Figure 6).
Active site in general Examination of the MTT and FMA-complexes shows that the active site can be divided into three regions: (1) the adenine, (2) the ribose, and (3) the 5' tail binding sites. The FMA and MTT-bound structures fully identifies the catalytic and binding residues in the active site. Please note for ease of comparison, the numbering of atoms in the purine base of the inhibitors (MTT and FMA) will be based on the numbering convention of MTA and not the IUPAC standard (Figure 10).
The adenine-binding site The adenine-binding site in MTAIAdoHcy nucleosidase involves [i-strand [i10 and the loop between [3-strand ~i8 and a-helix a4. This site is composed of the residues, Phe151, I1e152, Ser196, Asp197, and A1a199 (Figure 9a, 12a, and 13a). The binding site interactions involve predominantly mainchain hydrogen bond interactions, which is consistent with the K", being independent of the pH [31]. The phenyl ring of Phe151 makes a nearly perpendicular herringbone interaction with the adenine ring [32]. The distance between the C 1 atom of Phe151 and the plane of the adenine base is about 3.7 A. The mainchain carbonyl oxygen and amide nitrogen of I1e152 are in excellent hydrogen bonding distance to the amino group (N6) and N1 of the adenine base, respectively. Additional interactions exist between O_1 and O 2 of Asp197 and the N7 and the N6 amido group on the adenine moiety, respectively. Ser196 Oy and the amide nitrogen of A1a199 do not participate directly in the binding of the purine base but is thought to stabilize the sidechain of Asp197 so that it is in proper position over the purine N7.
Comparison of the adenine-binding sites The adenine-binding site closely resembles the binding site in the human MTAP
and E.
coli PNP structures. The herringbone type interaction made by a phenylalanine and the close proximity of an aspartate residue to N7 and N6 are observed in both classes of PNPs that are specific for 6-aminopurlnes. From the superimposition of the three structures, Phe151 and Asp197 appear to be structurally conserved in MTAP
(Phe177 and Asp220) and E. coil PNP (Phe159 and Asp204).
The major difference between the nucleosidase and PNPs is the size of the adenine-binding cavity. E. coii PNP has a more open purine-binding site compared to mammalian PNPs because the [i7-a5 loop has moved ~7-8 A away. The openness of the binding site is proposed to contribute to the enzyme's broader substrate specificity and decreased catalytic efficiency [29]. The nucleosidase active site is smaller than either the mammalian MTAP or E. coli PNP active site. The loop between strand [i8 and helix a4 is closer to the adenine ring than the analogous loop in MTAP
(~2 A closer) and hexameric PNP (~10 A closer). As a result the N1 and N6 positions of the adenine ring makes direct hydrogen bonds to the enzyme's mainchain rather than to sidechain atoms and water molecules as seen in the PNP and MTAP
structures.
The ribose-binding site The ribose-binding site is primarily made up of six residues, Met9, Ser76, Met173, GIu174, Arg193, and Phe207 (Figure 9b, 12b and 13). The ribose in both the MTT
and FMA complexed structures are anchored by both hydrogen bonds and van der Waals contacts. The hydrogen bonding network consists of four direct and one water-mediated hydrogen bond to the enzyme. Two hydrogen bonds are made by the O_1 and O 2 of GIu174 to the 03' and 02' hydroxyls of the ribose, respectively. A
third hydrogen bond is made from the backbone amide hydrogen of Met173 to the 02' hydroxyl of the ribose, while the hydrophobic sidechain of Met173 packs against the hydrophobic face of the ribose moiety. It is thought that this interaction helps stabilize and properly orients the sugar. The fourth direct hydrogen bond is made between the Oy hydrogen of Ser76 and the 04' position of the ribose. The water-mediated hydrogen bond interactions are between WAT3 and the 02' and 03' ribosyl hydroxyls. Van der Waals contacts are made between Met9 S8 and C_ and the 04' and C4' positions of the ribose, respectively. In addition, Phe207 Cz makes a van der Waals interaction to the C4' position.
Comparison of the ribose-binding sites The binding of the ribose moiety in the nucleosidase is completely different from that seen in the trimeric (mammalian) PNPs but is, in part, similar to E. coli PNPs. In MTAP, a phosphate anion rather than a glutamic acid residue coordinates the 02' and 03' hydroxyls of the ribose. In E. coli PNP, the 02' hydroxyl of the ribose hydrogen bonds to the O 2 of GIu181 and the 03 phosphate, while the 03' hydroxyl makes hydrogen bond interactions to the O_1 of GIu181 and the 02 phosphate. The interactions of the ribose hydroxyls and GIu181 are similar to that seen in the nucleosidase. The phosphate oxygen (03) in E. coli PNP is in close proximity to the proposed catalytic water (WAT3) in the nucleosidase. In both classes of phosphorylase, the phosphate is stabilized through a number of favorable charge-charge interactions and although the nucleosidase contains a cavity that could potentially fit a phosphate anion, the enzyme lacks the residues necessary for binding a phosphate anion [33]. For example Arg60 and Thr93 in human MTAP are replaced by Ser48 and GIy75, respectively in the nucleosidase. The nucleosidase is also missing the phosphate-binding His61 and Thr18 residues. In E. coli PNP, the phosphate-enzyme interactions include residues GIy20, Arg24, Arg43, His62, Arg87, and Ser90. His62 and Arg43 are replaced in the nucleosidase by Ser48 and GIy30, respectively, while Arg87 is replaced by Asn73. In addition, in E, coli PNP
residues GIy20 and Arg24 are found in helix a1, a helix that is not structurally conserved in the nucleosidase structure (Figure 8). E. coli PNP Ser90 is the only residue conserved in the nucleosidase (Ser76).
5 =tail binding site The 5'-methylthio tail of MTT is primarily coordinated by hydrophobic interactions. This 5' tail pocket is made up of residues Met9, IIs50, Va1102, Phe105, Pro113, Phe151, Met173, and Phe207 (Figure 12b + 13b). These residues make van der Waals interactions to the 5' tail and form a well defined hydrophobic pocket.
Residues Va1102, Phe105 and Pro113 are donated from a neighbouring monomer. Tyr107 was originally thought to be a part of the hydrophobic pocket but in the MTT and FMA-complexed structures, Tyr107 is ~6 A to the methyl moiety of the 5' tail in MTT.
Although Tyr107 seems to be too far to play a major role in the binding of the methylthio group, the Orl of Tyr107 could still potentially hydrogen bond the carboxylic acid or amino group of the homocysteinyl moiety of AdoHcy.
Comparison of fhe 5' tail binding site The binding of the 5' tail is different between the human MTAP and the nucleosidase.
In human MTAP, residues Phe177, Va1233, Va1236, and Va1237, and Leu279 and His137 from a neighbouring subunit make van der Waais contacts to the 5'-tail.
Va1233, Va1236, and Va1237 are part of a-helix a6 in MTAP. This helix in the nucleosidase structure is one turn shorter at the N-terminus and thus eliminates part of the hydrophobic region seen in MTAP (residues Va1233, Va1236, and Va1237).
The nucleosidase is also missing structurally equivalent counterparts for residues Leu279 and His137. In the nucleosidase structure, residues Met9, IIe50, Met173, and Phe207 plus Va1102, Phe105, Tyr107, and Phe113 from the neighbouring monomer likely forms a hydrophobic region used to bind the 5'-tail. The helix truncation of a6 and the loss of Leu279 and His137 explain the ability of the nucleosidase to exhibit dual substrate specificity for MTA and AdoHcy.
Conformation of the nucleosides Based on NMR experiments, MTA and AdoHcy are found predominantly in the anti-conformation and exhibit a glycosidic torsion angle of 45° (C8-N9-C1'-44'). The MTT
and FMA nucleosides are found in a high syn-conformation relative to the gfycosidic bond. This energetically unfavorable orientation of the substrate puts strain on the substrate and favours the formation of the transition state. In the human MTAP
structure, bound MTA also exhibited a glycosidic torsion angle of -54°.
MTAlAdoHcy nucleosidase binds nucleosides in a similar glycosidic conformation to those in MTAP
and PNP enzymes. In the FMA and MTT-bound structures, FMA and MTT have glycosidic torsion angles of -68° and -64°, respectively. The superimposition of the bound MTA, FMA and MTT structures comfirm the similarity in the glycosidic torsion angle (Figure 14). However, the superimposition reveals differences in the torsion angles of the 5' tail. MTA-bound in the human MTAP structure has a 5' tail torsion angle (C4-C5-S5-CS) of 39°, while MTT in the nucleosidase has a torsion angle of -68°.
Conformational changes A detailed comparison of the adenine, MTT and FMA-bound nucleosidase structures have been carried out to determine any conformational changes that occur on substrate binding. The structures are superimposed using residues in the central ~i-sheet as described in the experimental procedures. A superimposition of the dimeric FMA and MTT inhibitor complexes revealed an overall root mean square deviation (rmsd) of 0.3 A for the mainchain atoms (N-Ca-C). The two structures are virtually identical and for the purpose of the following discussion, we have used the MTT
complex as the representative model to describe the structural changes observed. A
rmsd plot of all Ca atoms in the monomer of the adenine and MTT complexed structures highlights regions of intrasubunit stnrctural deviation (Figure 15). As an additional check on the validity of our superimposition, the adenine-bound structure was superimposed onto the MTT-camplexed structure based on the adenine moiety.
The rmsd plot of the Ca positions shows similar regions with conformational changes.
Stereo van der Waals diagrams (Figure 12c) before and after binding MTT reveal the closure of the active site and a will defined hydrophobic pocket.
Adenine-binding site conformational changes The comparison of the adenine and MTT-bound structures of MTA/AdoHcy nucleosidase revealed numerous backbone and sidechain movements (Figure 16).
The largest movement is a loop to helix transition in residues 199-207. In the adenine-bound nucleosidase structure (1JYS), the electron densities for residues 202-were either weak or missing. These residues were disordered in a solvent exposed region of the enzyme. Upon binding of MTT or FMA, residues 200-211 form an extension to the existing a6 helix, with t_eu211 being the point at which the kink occurs. This extended a6 helix is not continuous as the extension is at a ~45° angle (Figure 16b). This conformational change results in a closing of the active site by moving residues 199-201 into the adenine-binding site where they make key hydrogen bonds to the enzyme, as described above. The amide nitrogen of A1a199 moves approximately 2 A to make a hydrogen bond to Asp197 O 2. This hydrogen bond between Asp197 and A1a199 and one made between Asp197 O_1 and Ser196 OY is thought to reposition the sidechain of Asp197 closer to the N7 atom of the purine ring.
The extension of the a6 helix and the additional hydrogen bonds made by A1a199 are proposed to be important in closing the adenine-binding cavity. The hydrogen bonding between the carbonyl oxygen of A1a199 and the amide nitrogen of G1y154 may serve to pull in residues 150-152 and hence shrink the adenine-binding cavity. From the superimposition, residues 150-152 were found to shift by approximately ~1.2 A
(Figure 16c).
The adenine molecule seen in the 1JYS structure is loosely bound as can be seen by the long hydrogen bond between the Asp197 and the N7 adenine (~3.9 A) and by the higher average B-factors for the adenine (~55 A2) than the average overall B-factors in the rest of the protein (33.7 AZ). The hydrogen bond between the N7 of the purine ring and the O_ hydrogen of Asp197 in the FMA-complexed structure is now 2.7 A
(Figure 13a) and thus forms a stronger hydrogen bond. The extension of the a6 helix (residues 200-211 ) also allows the residue Phe207 to move approximately 7.5 A
towards the 5'-tail to help complete the hydrophobic pocket. Phe151 and Phe207 make a herringbone interaction to Phe105 of the neighbouring subunit. The binding of the substrate/inhibitor causes an induced conformational change to the adenine molecule.
Intramolecular 5' tai! binding site conformational changes A major intrasubunit conformational change involves a movement of residues 7-42.
Residues Met9 and GIu12 in the a1 helix undergo a movement into the active site upon ligand binding and this conformational change is propagated to residues in ~-strands, ~i1, X32, X33, and ~i4 (Figure 16d). Met9 is moved towards the 5'-tail binding site. The sidechain of Met9 packs against the 5'-methylthio group of MTT and helps create part of the hydrophobic pocket. GIu12 does not bind the substrate but hydrogen bonds a water molecule ('WAT3) that is in close proximity to the C1' position of MTT
(~3.5 A).
The conformational change of GIu12 creates hydrogen bonds to the amide hydrogen of Met9 and Ser76, and the Oy of Ser76. G1u12 is proposed to deprotonate the nucleophilic water required for the hydrolysis of the N9-C1' bond (see later discussion).
The importance of the N-terminal residues of MTAIAdoHcy nucleosidase was previously analyzed with a truncation mutant of the f;rst 8 residues. A high degree of sequence similarity exists with the first 8 residues of the human MTAP
(VKIGIIGG) and the E. coli MTAIAdoHcy nucleosidase (MKIGIIGA). Comell et al postulated that this region is involved in MTA binding. Kinetic analysis revealed that the first 8 residues are involved in substrate binding. Although the inhibitor-enzyme complexed structures show that residues 1-8 do not play a direct role in the binding of the substrate, elimination of these residues may affect the local stability of this region and hinder the conformational changes required in the a1 helix (residues Met9 and GIu12 in particular) for catalysis.
Intermolecular 5' tail binding site conformational changes MTA/AdoHcy nucleosidase is a dimer based on the donation of residues in the 100's ;t loop from a neighbouring subunit. At the 5' tail, residues Va1102, Phe105, Tyr107, and Pro113 make hydrophobic interactions to the methylthio or homocysteinyl tail.
The identity of these residues was determined using a superimposed modeled of MTA
taken from the human MTAP structure. However, the modeled MTA molecule revealed that Tyr107, Pro113, and Va1102 are approximately 8.2 A, 7.2 A, and 6.2 A, respectively, away from the nearest atom in the 5' tail. This showed that an inter subunit conformational change was needed to bring the residues into van der Waals contacts. The only residue modeled close enough to the 5' tail position of the substrate was Phe105 (4.2 A).
The Ca superimpostion of the aderyne and M1T-bound dimer reveals a conserved dimer interface (Figure 17a). Upon further inspection, the 1005 Poop containing the donated residues w as not found to undergo a major conformational charge but rather a smaler loop translation by only some of the donated residues (Figure 17b). Residues Va1102 and Pro113 do not seem to undergo a conformational charge but residues Phe105 and Tyr107 moves ~1.5 A closer to the methylthio group in both cases. This result is not surprising given that the 5' tail of the nucleoside is in a different conformation than that seen in the MTA bound in human MTAP Residues Va1102, Phe105, and Pro113 are all in good van der Waah proxirrity to the methylthio tail of MTT. Even w ith the conformational charges seen in Tyr107, this residue is stil too far to make van der Waat~
contacts w ith the methyfthio group (5.8 A). How ewer Tyr107 O could hydrogen bond w ith the carboxyl moiety of a longer homocysteine group fromAdol-Ey.
lm picatior~s for catalys is MTA/AdoHcy nucleosidase is an inverting hydrolase that cleaves the glyoosidic Nnlage between the C1' postion of MTA or AdoHcy and the N9 of the aderine ring In addtion to hav~g a simiar overall topdogy to the hexameric and trirreric PNPs, the nucleosidase also shares a simiar enzymatic mechanism The Pl~enzymatic mechanism is proposed to be the same for enzymes that cleave nucleosides w ith &oxopurines (human and bovbe PNP) and 6-arrinopurbes (human MTAi~. The human PNP, human MTAP, and bovbe PNP react'rons are generally thought to proceed via a tw o-step mechanism w ith the formation of an oxocarbenium transition-state folbwed by a nucleophilic attack by the phosphate anion at the anorreric carbon in an SN-1 type mechanism [27, 34, 35].
Current biochemical data supports the formation of the oxocarbenium transition-state and an enzyme-mediated SN1-type nucleophilic attack for MTA/AdoHcy nucleosidase (31, 36, 37].
'The formation of the oxocarbenium trar~,sition-state requres the donation of a proton to the M pos~ion of the aderrne ring. F~esdue Asp197 is located in close proximity to the M aderrne pos~ion and is potentially involved in prothn donation. At physiological pH, an aspartate residue is theoretically deprotonated (free p1(8 ~~4.5) how ever, burial of aspartate has been shown to raise the plCa in the enzyme thioredoxin (38].
Based on this observation, the structurally homdogous aspartate (Asp220) in the MTAPstructure has a raised pKa and act as the catalytic acid [27]. Irrespective of the souroe of the proton, Asp197 makes a strong hydrogen bond w ith N7. The electron deficient purhe base (electron pull is stat~ilized w ith a flow of electrons from the ribosyl 04' (electron push). h PhIP, the ribosyl 04' is sandw iched between the 5'-hydroxyl of the inosine substrate and the 04 phosphate. This favours the migration of electrons tow ads the base and elongation of the C1'-I~ bond to form the oxocarbenium transition-slate [35].
The eluadation of the FMA and MTT-bound structures revealed that the 5' tail sulfur is in a different conformation than the sulfur in MTAP and PtW' (figure 14). The ribosyl 04' atomdoes notseemto be trapped between two electron rich groups. Ser7i6 Oy is the only electron rich group in proximity (3.5 A) to the 04' ribosyl moiety. This shows that the 5' sulfur has another role to play in the catalytic mechanism The 5' tail sulfur could be involved in directing the conformational changes seen in the a1 helot region.
How ever, another electron rich molecule in proximity to the ribosyl 04' is the nucleophilic w ater, WAT3. This w ater molecule stabilizes the partial pos~ive charge buit up at the 04' pos~ion in the transition state, in a simiar fashion to the 04 phosphate seen in the human MTAPstructure. It is unclear w hether the ribosyl 04' atom needs to be trapped between tw o electron rich groups to push the electrons to the purhe base.
The second step of the mechanism involves an enzyme directed nucleophilic attack by water on the oxocarbenium transition-state (31, 36]. Analysis of the FMA
and MTT
bound structures, reveals that WAT3 is clearly the nucleophilic water, as this molecule is in excellent position and distance to the anomeric carbon (3.6 A) (Figure 18). In addition, WAT3 is hydrogen bonded to GIu12, which is deprotonated.
This shows that GIu12 is the catalytic base and that activation of the nudeophile is necessary for catalysis.
The MTT bound structure has also revealed a proton relay system involving the nucleophilic water (WAT3) and residues GIu12, Ser76, Ser196, and Asp197 (Figure 18). All four proposed residues are absolutely conserved between the different species of MTA/AdoHcy nucteosidase. This proton relay system assumes that Asp197 is protonated. After proton donation by Asp197 to the N7 position, Asp197 O_1 could remove a proton off the Ser196 Oy, which could then in turn take a proton off the Ser76 Oy. In the MTT-bound structure, Ser76 and Ser196 are too far from one another (4.0 A) to transfer a proton. However, a rotation about x~ in either Ser76 or Ser196 may bring the sidechains into closer proximity. Ser76 can be easily re-protonated by a protonated GIu12 O_1. Since glutamates have a pKa = 4.3, the proton from GIu12 should be readily given up. The deprotonation of GIu12 will put it back into its catalytically active state, ready to activate another nucleophilic water.
Substrate specificity A previous analysis of over 20 nucleoside analogs has provided insight into the substrate characteristics required for recognition [3~. MTAlAdoHcy nucleosidase has preference for a 6-amino purine group, an intact ribose, and an uncharged sulfur atom at the 5' tail [3]. The substrate preference for a 6-amino purine ring and 2' and 3'-hydroxyls on the ribose can be clearly explained by hydrogen bonding interactions to these positions, as described previously. The requirement for a neutral sulfur atom is not as easily explained. However, the comparison of the FMA and MTT-complexed nucleosidase structure reveals differences that may explain the requirement for a 5' tail sulfur. The catalytic base, GIu12 has a different conformation in the FMA
as compared to the MTT-complexed nucleosidase structure. In the MTT-bound structure, GIu12 O 1 makes hydrogen bond interactions to the amide nitrogen of Ala8 and Met9 and WAT3. Hydrogen bonds anchor GIu12 O_2 to WAT3, Ser76 Oy and Ser76 amide nitrogen. The posi~oning of GIu12 in the MTT-bound structure is in the catalytically active state, as GIu12 is in position to activate the nucleophilic water and be able to facilitate a proton transfer mechanism through Ser76 and Ser196 to Asp197. In the FMA-complexed structure, GIu12 has a different conformation to the one seen in the MTT-bound structure. To complicate matters further, G1u12 has two conformations in the dimer. In monomerA, GIu12 is located away from the active site and makes six hydrogen bonds to the enzyme. GIul2 O 1 is hydrogen bonded to Thr74 Orl, Ser218 Oy, and Ser219 N while G1u12 O 2 is hydrogen bonded to GIy75 N, Thr74 OY1, and Ser218 Oy. GIu12 is thought to be in an inactive state, as it fails to interact with the nudeophilic water and Ser76 for proton transfer. In monomerB, GIu12 is found closer to the active site and has hydrogen bond interactions to two partners, the amide nitrogen of Met9 and WAT3 (nucleophilic water). Although GIu12 hydrogen bonds to the nudeophilic water (WAT3) in monomer B, GIul2 is still in a catalytically inactive state because the proton relay system is disrupted by the lack of a hydrogen bonding distance to Ser76 Oy. The binding of ligands with 5' hydroxyls disrupts the proper positioning of the catalytic base, G1u12. This accounts for the decrease in activity for 5'-hydroxyl containing nucleosides, like adenosine. The Ca backbone of the FMA-bound structure superimposes very well to the MTT-bound structure. The neutral 5'-tail sulfur may stabilize GIu12 into the catalytically active conformation.
Structures of MTAIAdoHcy nuclsosidase from pathogenic species The structures of the pathogenic species of MTAIAdoHcy nucleosidase reveal a conserved overall topology to the E. coli nucleosidase. Each monomer of the S.
aureus and S, pneumoniae has a mixed nine-stranded central ~-sheet, flanked by six a-helices and a small 3~o helix. The electron density map revealed the unambiguous presence of an 8-aminoadenine and Formycin A ligand in the S. pneumoniae and S.
aureus structures, repsectively. The identification of active site residues were based on the positions of these ligands. The active site residues involved in binding and catalysis are primarily conserved with the residues in the E. coli nucleosidase.
Streptococcus pneumoniae Adenine binding site- Ser76, Phe151, I1e152, Ser196, Asp197, A1a199 The ribose and 5'-tail binding sites are similar to the E. coli ribose and 5' tail binding sites.
Ribose binding site- Met9, Ser76, Met173, GIu174 5'-tail binding site- Met9, IIe50, Phe151, Met173, Phe207 and (Va1102, Phe105, Tyr107, and A1a113). The residues in brackets are from the neighbouring monomer Staphylococcus aursus Adenine binding site- Ser75, Phe150, I1e151, Ser195, Asp196, and A1a198 Ribose binding site- MetB, Ser75, Met172, GIu173 5'-tail binding site- Met8, I1e49, Phe150, Met172, Phe206 and (AIa101, Phe104, Tyr106, and Pro112). The residues in the brackets are from the neighbouring monomer.
Table 6 shows coordinates of Streptococcus pneumoniae complexed with 8-aminoadenosine. However from the electron density, the 8-aminoadenosine is cleaved and only an 8-aminoadenine molecule is seen in the active site. Table 5 shows coordinates of Staphylococcus aureus complexed to Formycin A.
Applicants' invention has provided, for the first time, information about the shape and structure of the MTA/AdoHcy nucleosidase and its active site.
Active sites are of significant utility in fields such as drug discovery. The association of natural substrates with the active sites of their corresponding enzymes is the basis of many biological mechanisms of action. Similarly, many drugs exert their biological effects through association with the active sites of receptors and enzymes. Such associations may occur with all or any parts of the active site. An understanding of such associations helps lead to the design of drugs having more favorable associations with their target, and thus improved biological effects. Therefore, this information is valuable in designing inhibitors of MTA/AdoHcy nucleosidase, as discussed in more detail below.
A "complex" means MTA/AdoHcy nucleosidase in covalent or non-covalent association with a chemical entity or compound. The term "binding site" as used herein, refers to a region of a molecule or molecular complex, that as a result of its shape, favorably associates with another chemical entity. A binding site may include or consist of features such as cavities, surfaces, or interfaces between domains. Chemical entities that may associate with a binding site include, but are not limited to, substrates and inhibitors.
Three-Dimensional Configurations X-ray structure coordinates define a unique configuration of points in space.
Those of skill in the art understand that a set of structure coordinates for protein or an protein/ligand complex, or a portion thereof, define a relative set of points that, in tum, define a configuration in three dimensions. A similar or identical configuration can be defined by an entirely different set of coordinates, provided the relative distances and angles between coordinates remain essentially the same.
The configurations of points in space derived from structure coordinates according to the invention can be visualized as, for example, a holographic image, a stereodiagram, a model or a computer-displayed image, and the invention thus includes such images, diagrams or models.
Structurally Equivalent Crystal Structures Various computational analyses can be used to determine whether a molecule or the active site portion thereof is "structurally equivalent," defined in terms of its three-dimensional structure, to all or part of MTA/AdoHcy nucleosidase or its binding sites.
Such analyses may be carried out in current software applications, such as the Molecular Similarity application of QUANTA (Molecular Simulations Inc., San Diego, Calif.) version 4.1, and as described in the accompanying User's Guide.
The Molecular Similarity application permits comparisons between different structures, different conformations of the same structure, and different parts of the same structure. The procedure used in Molecular Similarity to compare structures is divided into four steps: (1) load the structures to be compared; (2) define the atom equivalences in these structures; (3) perform a fitting operation; and (4) analyze the results.
Each structure is identified by a name. One structure is identified as the target (i.e., the fixed structure); all remaining structures are working structures (i.e., moving structures). Since atom equivalency within QUANTA is defined by user input, for the purpose of this invention equivalent atoms are defined as protein backbone atoms (N, C.alpha., C, and O) for all conserved residues between the two structures being compared. A conserved residue is defined as a residue that is structurally or functionally equivalent. Only rigid fitting operations are considered.
When a rigid fitting method is used, the working structure is translated and rotated to obtain an optimum fit with the target structure. The fitting operation uses an algorithm that computes the optimum translation and rotation to be applied to the moving structure, such that the root mean square difference of the fit over the specified pairs of equivalent atom is an absolute minimum. This number, given in angstroms, is reported by QUANTA.
For the purpose of this invention, any molecule or molecular complex or active site thereof, or any portion thereof, that has a root mean square deviation of conserved residue backbone atoms (N, Ca, C, O) of less than about 1.5 A, when superimposed on the relevant backbone atoms described by the reference structure coordinates listed in the tables, is considered "structurally equivalent" to the reference molecule.
That is to say, the crystal structures of those portions of the two molecules ace substantially identical, within acceptable error. Particularly preferred structurally equivalent molecules or molecular complexes are those that are defined by the entire set of structure coordinates listed in the tables, plus/minus a root mean square deviation from the conserved backbone atoms of those amino acids of not more than 1.5 A. More preferably, the root mean square deviation is less than about 1.0 A or 0.5 A.
The term "root mean square deviation" means the square root of the arithmetic mean of the squares of the deviations. It is a way to express the deviation or variation from a trend or object. For purposes of this invention, the "root mean square deviation"
defines the variation in the backbone of a protein from the backbone of MTA/AdoHcy nucleosidase or a binding site portion thereof, as defined by the structure coordinates of MTA/AdoHcy nucleosidase described herein.
Structurally Homologous Molecules, Molecular Complexes, and Crystal Structures The structure coordinates can be used to aid in obtaining structural information about another crystallized molecule or molecular complex. The method of the invention allows determination of at least a portion of the three-dimensional structure of molecules or molecular complexes which contain one or more structural features that are similar to structural features of MTAIAdoHcy nucleosidase. These molecules are referred to herein as "structurally homologous" to MTA/AdoHcy nucleosidase.
Similar structural features can include, for example, regions of amino acid identity, conserved active site or binding site motifs, and similarly arranged secondary structural elements (e.g., a-helices and ~i-sheets). Optionally, structural homology is determined by aligning the residues of the two amino acid sequences to optimize the number of identical amino acids along the lengths of their sequences; gaps in either or both sequences are permitted in making the aligmnent in order to optimize the number of identical amino acids, although the amino acids in each sequence must nonetheless remain in their proper order. Preferably, two amino acid sequences are compared using the Blastp program, version 2Ø9, of the BLAST 2 search algorithm, as described by Tatusova et al., FEMS Microbiol Lett 174, 247-50 (1899), and available at http://www.ncbi.nlm.nih.gov/gorflb12.html. Preferably, the default values for all BLAST 2 search parameters are used. In the comparison of two amino acid sequences using the BLAST search algorithm, structural similarity is referred to as "identity." Preferably, a structurally homologous molecule is a protein that has an amino acid sequence sharing at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity with a native or recombinant amino acid sequence of MTA/AdoHcy nucleosidase. More preferably, a protein that is structurally homologous to MTA/AdoHcy nucleosidase includes at feast one contiguous stretch of at least 25 or 50 amino acids that shares at least 80% amino acid sequence identity with the analogous portion of the native or recombinant MTA/AdoHcy nucleosidase.

Methods for generating structural information about the structurally homologous molecule or molecular complex are well-known and include, for example, molecular replacement techniques.
Therefore, in another embodiment this invention provides a method of utilizing molecular replacement to obtain structural information about a molecule or molecular complex whose structure is unknown comprising the steps of:
(a) crystallizing the molecule or molecular complex of unknown structure;
(b) generating an x-ray diffraction pattern from said crystallized molecule or molecular complex; and (c) applying at least a portion of the structure coordinates to the x-ray diffraction pattern to generate a three-dimensional electron density map of the molecule or molecular complex whose structure is unknown.
By using molecular replacement, all or part of the structure coordinates of MTA/AdoHcy nucleosidase or a MTA/AdoHcy nucleosidase complex as provided by this invention can be used to determine the structure of a crystallized molecule or molecular complex whose structure is unknown more quickly and efficiently than attempting to determine such information ab initio.
Molecular replacement provides an accurate estimation of the phases for an unknown structure. Phases are a factor in equations used to solve crystal structures that cannot be determined directly experimentally. Obtaining accurate values for the phases, by methods other than molecular replacement, is a time-consuming process that involves iterative cycles of approximations and refinements and greatly hinders the solution of crystal structures. However, when the crystal structure of a protein containing at least a structurally homologous portion has been solved, the phases from the known structure provide a satisfactory estimate of the phases for the unknown structure.
Thus, this method involves generating a preliminary model of a molecule or molecular complex whose structure coordinates are unknown, by orienting and positioning the relevant portion of MTAIAdoHcy nucleosidase or the complex according to the structure coordinates listed within the unit cell of the crystal of the unknown molecule or molecular complex so as best to account for the observed x-ray diffraction pattern of the crystal of the molecule or molecular complex whose structure is unknown.
Phases can then be calculated from this model and combined with the observed x-ray diffraction pattern amplitudes to generate an electron density map of the structure whose coordinates are unknown. This, in turn, can be subjected to any well-known model building and structure refinement techniques to provide a final, accurate structure of the unknown crystallized molecule or molecular complex (E.
Lattman, "Use of the Rotation and Translation Functions," in Meth. Enzymol., 115, pp.

(1985); M. G. Rossman, ed., 'The Molecular Replacement Method," Int. Sa. Rev.
Ser., No. 13, Gordon 8~ Breach, New York (1972)).
Structural information about a portion of any crystallized molecule or molecular complex that is sufficiently structurally homologous to a portion of MTAIAdoHcy nucleosidase can be resolved by this method. In addition to a molecule that shares one or more structural features with MTA/AdoHcy nucleosidase as described above, a molecule that has similar bioactivity, such as the same catalytic activity, substrate specificity or ligand binding activity as MTA/AdoHcy nucleosidase, may also be sufficiently structurally homologous to MTA/AdoHcy nucieosidase to permit use of the structure coordinates of MTAIAdoHcy nucleosidase to solve its crystal structure.
In a preferred embodiment, the method of molecular replacement is utilized to obtain structural information about a molecule or molecular complex, wherein the molecule or molecular complex comprises at least one MTA/AdoHcy nucleosidase fragment or homolog. A "fragment" of MTA/AdoHcy nucleosidase is an MTA/AdoHcy nucleosidase molecule that has been truncated at the N-terminus or the C-terminus, or both.
In the context of the present invention, a "homolog" of MTA/AdoHcy nucleosidase is a protein that contains one or more amino acid substitutions, deletions, additions, or rearrangements with respect to the amino acid sequence of MTAIAdoHcy nucleosidase, but that, when folded into its native conformation, exhibits or is reasonably expected to exhibit at least a portion of the tertiary (three-dimensional) structure of MTA/AdoHcy nucleosidase. For example, structurally homologous molecules can contain deletions or additions of one or more contiguous or noncontiguous amino acids, such as a loop or a domain. Structurally homologous molecules also include "modified" MTAIAdoHcy nucleosidase molecules that have been chemically or enzymatically derivatized at one or more constituent amino acid, including side chain modfications, backbone modifications, and N- and C
terminal modifications including acetylation, hydroxylation, methylation, amidation, and the attachment of carbohydrate or lipid moieties, cofactors, and the like.
A heavy atom derivative of MTA/AdoHcy nucleosidase is also included as an MTA/AdoHcy nucleosidase. The term "heavy atom derivative" refers to derivatives of MTAIAdoHcy nucleosidase produced by chemically modifying a crystal of MTA/AdoHcy nucleosidase. In practice, a crystal is soaked in a solution containing heavy metal atom salts, or organometallic compounds, e.g., lead chloride, gold thiomalate, thiomersal or uranyl acetate, which can diffuse through the crystal and bind to the surface of the protein. The locations) of the bound heavy metal atoms) can be determined by x-ray diffraction analysis of the soaked crystal. This information, in turn, is used to generate the phase information used to construct three-dimensional structure of the protein (T. L. Blundeil and N. L. Johnson, Protein Crystallography, Academic Press (1976)).
Because MTAIAdoHcy nucleosidase can crystallize in more than one crystal form, the 1C1 structure coordinates of MTA/AdoHcy nucleosidase as provided by this invention are particularly useful in solving the structure of other crystal forms of MTA/AdoHcy nucleosidase or MTAIAdoHcy nucleosidase complexes.
The structure coordinates of MTAIAdoHcy nuGeosidase as provided by this invention are particularly useful in solving the structure of MTA/AdoHcy nucleosidase mutants.
Mutants may be prepared, for example, by expression of MTAIAdoHcy nucleosidase cDNA previously altered in its coding sequence by oligonucieotide-directed mutagenesis. Mutants may also be generated by site-specific incorporation of unnatural amino acids into MTAIAdoHcy nucleosidase proteins using the general biosynthetic method of C. J. Noren et al., Science, 244:182-188 (1989). In this method, the colon encoding the amino acid of interest in wild-type S. MTA/AdoHcy nucleosidase is replaced by a "blank" nonsense colon, TAG, using oligonucleotide-directed mutagenesis. A suppressor tRNA directed against this colon is then chemically aminoacylated in vitro with the desired unnatural amino acid. The aminoacylated tRNA is then added to an in vitro translation system to yield a mutant a2 5 with the site-specific incorporated unnatural amino acid.
The structure coordinates of MTAIAdoHcy nucleosidase are also particularly useful to solve the structure of crystals of MTA/AdoHcy nucleosidase, MTA/AdoHcy nucleosidase mutants or MTAIAdoHcy nucleosidase co-complexed with a variety of chemical entities. This approach enables the determination of the optimal sites for interaction between chemical entities, including candidate MTA/AdoHcy nucleosidase inhibitors and MTA/AdoHcy nucleosidase. Potential sites for modification within the various binding site of the molecule can also be identified. This information provides an additional tool for determining the most efficient binding interactions, for example, increased hydrophobic interactions, between MTA/AdoHcy nucleosidase and a chemical entity. For example, high resolution x-ray diffraction data collected from crystals exposed to different types of solvent allows the determination of where each type of solvent molecule resides. Small molecules that bind tightly to those sites can then be designed and synthesized and tested for their MTA/AdoHcy nucleosidase inhibition activity.
All of the complexes referred to above may be studied using well-known x-ray diffraction techniques and may be refined versus 1.5-3.0 A resolution x-ray data to an R value of about 0.20 or less using computer software, such as CNS. This information may thus be used to optimize known MTAIAdaHcy nucleosidase inhibitors, and more importantly, to design new MTA/AdoHcy nucleosidase inhibitors.
The invention also includes the unique three-dimensional configuration defined by a set of points defined by the structure coordinates for a molecule or molecular complex structurally homologous to MTAIAdoHcy nucieosidase as determined using the method of the present invention, structurally equivalent configurations, and magnetic storage media comprising such set of structure coordinates.
Further, the invention includes structurally homologous m~ecules as identified using the method of the invention.
Homology Modeling Using homology modeling, a computer model of an MTAIAdoHcy nucJeosidase can be built or refined without crystallizing the homolog. First, a preliminary model of the MTA/AdoHcy nucleosidase is created by sequence alignment with MTAIAdoHcy nucleosidase, secondary structure prediction, the screening of structural libraries, or any combination of those techniques. Computational software may be used to cant' out the sequence alignments and the secondary structure predictions.
Structural incoherences, e.g., structural fragments around insertions and deletions, can be modeled by screening a structural library for peptides of the desired length and with a suitable conformation. For prediction of the side chain conformation, a side chain rotamer library may be employed. Where the MTAIAdoHcy nucleosidase has been crystallized, the final homology model can be used to solve the crystal structure of the homolog by molecular replacement, as described above. Next, the preliminary model is subjected to energy minimization to yield an energy minimized model. The energy ~0 minimized model may contain regions where stereochemistry restraints are violated, in which case such regions are remodeled to obtain a final homology model.

Drug Design of Inhibitors Inhibitors Inhibitors of MTA/AdoHcy nucleosidase provide a basis for diagnosis and/or treatment of enzyme-related pathologies. "Pathology" includes a disease, a disorder and/or an abnormal physical state caused by bacteria having MTAIAdoHcy nucleosidase. The structures are useful in the design of inhibitors, which may be used as therapeutic or prophylactic compounds for treating pathologies in which downregulation of enzyme activity is beneficial. It will be apparent that methods using enzyme described below may be readily adapted for use with a fragment of enzyme or an enzyme variant.
The characterization of the novel active site permits the design of potent, highly selective inhibitors. Several approaches can be taken for the use of the structure in the rational design of inhibitors. A computer-assisted, manual examination of a inhibitor binding site or active site structure may be done.
Rational Drug Design Computational techniques can be used to screen, identify, select and design chemical entities capable of associating with MTAIAdoHcy nucleosidase or structurally homologous molecules. Knowledge of the structure coordinates for MTA/AdoHcy nucleosidase permits the design and/or identification of synthetic compounds and/or other molecules which have a shape complementary to the conformation of an MTA/AdoHcy nucleosidase binding site. In particular, computational techniques can be used to identify or design chemical entities, such as inhibitors, agonists and antagonists, that associate with an MTA/AdoHcy nucleosidase binding site or an MTA/AdoHcy nucleosidase-like binding site. Inhibitors may bind to or interfere with all or a portion of the active site of MTA/AdoHcy nucleosidase, and can be competitive, non-competitive, or uncompetitive inhibitors. Once identified and screened for biological activity, these inhibitors/agonists/antagonists may be used therapeutically or prophylactically to block MTAIAdoHcy nucleosidase activity and, thus, inhibit the growth of the bacteria or cause its death. Structure-activity data for analogs of ligands that bind to or interfere with MTAIAdoHcy nucleosidase or MTAIAdoHcy nucleosidase -tike binding sites can also be obtained computationally.
Accordingly, the invention includes a method of designing a compound that inhibits MTA/AdoHcy nucleosidase activity, comprising performing rational drug design with a 3D structure of MTA/AdoHcy nucleosidase or fragment thereof to design a compound that interacts with the 3D structure of MTA/AdoHcy nucleosidease or fragment thereof and inhibits MTA/AdoHcy nucleosidase activity.
The invention also includes a method of identifying whether a compound inhibits MTA/AdoHcy nucleosidase activity, comprising performing rational drug design with a 3D structure of MTA/AdoHcy nucleosidase or fragment thereof, the drug design comprising i) comparing the 3D structure of the compound to the 3D structure of MTA/AdoHcy nucleosidase or fragment thereof and ii) determining whether the compound interacts with the 3D structure of MTA/AdoHcy nucleosidease and inhibits MTA/AdoHcy nucleosidase activity.
1 CI The 3D structure of MTA/AdoHcy nucleosidase or fragment thereof optionally comprises i) an active site ii) a 5' binding cavity and/or iii) a ribose binding site. The rational drug design optionally comprises comparing the structural coordinates of the compound to the structural coordinates of at least one of i) to iii) and determining whether the compound fits spatially into at least one of i) to iii) and is capable of a) changing MTA/AdoHcy nucleosidase from an open conformation to a closed conformation without nucleoside catalysis;
b) biasing MTA/AdoHcy nucleosidase toward a closed conformation; or c) preventing MTA/AdoHcy nucleosidase from changing toward a transition conformation or a closed conformation; wherein the ability of the compound to cause 2C/ any of a) to c) indicates that the compound inhibits MTA/AdoHcy nucleosidase activity.
In the method, the 3D structure is optionally determined from one or more sets of nucleosidase structural coordinates in Tables 1 to 6.
The drug design is preferably performed in conjunction with computer modeling 2fi comprising introducing into a computer program structural coordinates defining an MTA/AdoHcy nucleosidase or fragment thereof, wherein the program generates the 3D structure of the MTA/AdoHcy nucleosidase or fragment.
The MTA/AdoHcy nucleosidase preferably comprises E. coli MTA/AdoHcy nucleosidase, S. aureus MTA/AdoHcy nucleosidase or S, pneumoniae MTA/AdoHcy 3U nucleosidase.
The E. coli MTA/AdoHcy nucleosidase optionally comprises all or part of the amino acid sequence shown in Figure 19 (SEQ ID N0:1) or a structurally equivalent or structurally homologous sequence having at least 60% sequence identity to (SEQ
ID
N0:1);
The S. aureus MTA/AdoHcy nucleosidase optionally comprises all or part of the amino acid sequence shown in Figure 19 (SEQ ID NO:2) or a structurally equivalent or structurally homologous sequence having at least 60% sequence identity to (SEQ
ID
N0:2); or The S. pneumoniae MTA/AdoHcy nucleosidase optionally comprises all or part of the amino acid sequence shown in Figure 19 (SEQ ID N0:3) or a structurally equivalent or structurally homologous sequence having at least 60°~ sequence identity to (SEQ ID
'10 N0:3).
In the method, the compound that inhibits MTA/AdoHcy nucleosidase preferably has a greater affinity for the active site of MTA/AdoHcy nuGeosidase than does 5'-methylthioadenosine or S-adenosylhomocysteine.
In one embodiment, the 3D structure comprises an open conformation MTA/AdoHcy nucleosidase or fragment thereof or a structurally equivalent or structurally homologous conformation. The MTA/AdoHcy nucleosidase may comprise a subunit including a mixed ala domain comprising a nine-stranded mixed (3-sheet proximate to six a-helices and a 3,o helix.
In this embodiment, optionally:
a) the E. coli MTA/AdoHcy nucleasidase structure comprises the following amino acids:
i) adenine binding site: residues Phe151, I1e152, Ser196, Asp197, and A1a199;
ii) ribose binding site: residues GIu174, Ser76, Met9, Met173, Arg193, and Phe207;
iii) 5'-tail binding site: residues Met9, IIe50, (Va1102, Phe105, Tyr107, Pro113), Phe151, Met173, and Phe207, wherein the residues in brackets are donated from a neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Table 1;
b) the S. aureus MTA/AdoHcy nucleosidase structure comprises the following amino acids:
i) adenine binding site: Ser75, Phe150, I1e151, Ser195, Asp196, and A1a198;

ii) ribose binding site: MetB, Ser75, Met172, GIu173;
iii) 5'-tail binding site: MetB, I1e49, Phe150, Met172, Phe206 and (AIa101, Phe104, Tyr106, and Pro112), wherein the residues in the brackets are from a neighbouring monomer; the amino acids arranged in an open conformation spatial relationship represented by the structural coordinates listed in Table 5; and/or c) the S, pneumoniae MTA/AdoHcy nucleosidase structure comprises the following amino acids:
i) adenine binding site: Ser76, Phe151, 11e152, Ser196, Asp197, A1a199;
ii) ribose binding site: Met9, Ser76, Met173, GIu174; and/or iii) 5'-tail binding site: Met9, IIe50, Phe151, Met173, Phe207 and (Va1102, Phe105, Tyr107, and A1a113), wherein the residues in the brackets are from a neighbouring monomer; the amino acids arranged in an open conformation spatial relationship represented by the structural coordinates listed in Table 6.
All or some of these amino acids (and other nucleosidase amino acids described in this application) may be used. They may be used in modeling simultaneously or sequentially In another embodiment of the method, 3D structure of MTA/AdoHcy nudeosidase comprises a closed conformation MTA/AdoHcy nucleosidase or fragment thereof or a structurally equivalent or structurally homologous conformation. The MTA/AdoHcy nucleosidase may comprise a alai subunit including a nine-stranded mixed ~3-sheet and a five ~3-stranded sheet proximate to six a-helices and a 3,o helix.
In one aspect, the MTA/AdoHcy nucleosidase comprises E. coli MTA/AdoHcy nucleosidase complexed with FMA and the E. coli MTA/AdoHcy nucleosidase structure comprises the following amino acids:
i) adenine binding site: residues Phe151, I1e152, Ser196, Asp197, and A1a199;
ii) ribose binding site: residues GIu174, Ser76, Met9, Met173, Arg193, and Phe207;
and/or iii) 5'-tail binding site: residues Met9, IIe50, (Va1102, Phe105, Pro113) Phe151, Met173, and Phe207; wherein the residues in brackets are donated from a neighbouring monomer, the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Table 2.
In another aspect, the MTA/AdoHcy nucleosidase is complexed with MTT and the E.
coli MTAIAdoHcy nucleosidase structure comprises the following amino aads:
i) adenine binding site: residues Phe151, I1e152, Ser196, Asp197, and A1a199;
ii) ribose binding site: residues GIu174, Ser76, Met9, Met173, Arg193, and Phe207; or iii) 5'-tail binding site: residues Met9, IIe50, (Va1102, Phe105, Tyr107, Pro113), Phe151, Met173, and Phe207, wherein the residues in brackets are donated from a neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Table 3.
In another embodiment of the invention, the 3D structure used in the method comprises transition conformation MTA/AdoHcy nucleosidase or a fragment thereof or a conformation that is structurally equivalent or structurally homologous to the foregoing. Optionally, an E12A mutant MTA/AdoHcy nucleosidase is complexed to AdoHcy.
In one aspect of the method, the E. coli MTAIAdoHcy nucleosidase structure comprises the following amino acids:
i) adenine binding site: residues Phe151, IIe152, Ser196, Asp197, and A1a199;
ii) ribose binding site: residues G1u174, Ser76, Met9, Met173, Arg193, and Phe207;
andlor iii) 5'-tail binding site: residues Met9, IIe50, (Va1102, Phe105, Tyr107, Pro113,) Phe151, Met173, and Phe207, wherein the residues in brackets are donated from a neighbouring monomer; the amino acids an-angel in a spatial relationship represented by the structural coordinates listed in Table 4.
Selective Inhibitors Selective inhibitors may be obtained by comparing the interactions of an inhibitor with each of MTA/AdoHcy nucleosidase, MTA phosphorylase and AdoHcy hydrolase. h mammalian cells, the breakdown of MTA and AdoHcy requires two separate enzymes. MTA is catabolized in a reversible reaction to adenine and 5'-methylthioribose-1-phosphate (MTR-1-P) by MTA phosphorylase (MTAP), while AdoHcy is broken down to homocysteine and adenosine by AdoHcy hydrolase. h contrast, in microbes that are devoid of MTAP and AdoHcy hydrolase, the dual substrate-specific MTAIAdoHcy nucleosidase functions to recycle both nucleosides.
To selectively design inhibitors towards the bacterial enzyme requires a careful !i comparison between the human MTAP and human AdoHcy hydrolase enzymes to identify either active site residues or binding site regions that can be exploited. Two areas that can be exploited are at the 5' tail binding and the ribose-binding site.
In one embodiment, the method further comprises determining whether the compound interacts with the 3D structure of a PNP such as MTA phosphorylase or a fragment thereof and/or AdoHcy hydrolase or a fragment thereof and inhibits MTA
phosphorylase or AdoHcy hydrolase activity, wherein if the compound does not inhibit MTA phosphorylase or AdoHcy hydrolase activity, the compound is a selective inhibitor of MTA/AdoHcy nucleosidase. The fragment optionally comprises i) an active site ii) a 5' binding cavity and/or iii) a ribose binding site.
In one aspect, the MTA phosphorylase used in the method comprises the following amino acids:
i) adenine binding site: residues Phe177, Ser178, Thr219, Asp220 and Asp222;
ii) 5'-methylthioribose binding site: residues Met196, Va1233, Va1236, Leu237, (His237 and Leu279), wherein the residues in brackets are donated from a neighbouring subunit;
iii) sulfate/phosphate binding site: residues Thr18, Arg60, His61, Thr93, A1a94, and Thr197; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Protein Data Bank Accession No. 1 CG6.
In another aspect of the method, the AdoHcy hydrolase comprises the following amino acids i) adenine binding site: residues Leu54, Thr57, GIu59, SeMetIMet351, His353, and SeMet/Met358;
ii) ribose binding site: residues His55, GIu156, Lys186, Thr157, and Asp190 andJor iii) homocysteinyl binding site: His55, Cys79, Asn80, Asp131, Asp134, and Leu344;

the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Protein Data Bank Accession No. 1A7A.
According to one example of a method of the invention, the compound is a selective inhibitor of MTA/AdoHcy nucleosidase if:
i) the compound binds the ribose binding site of MTA/AdoHcy nucleosidase and inhibits MTA/AdoHcy nucleosidase activity and ii) the compound has a structure with at least one domain that would be capable of binding the compound to MTA phosphorylase and/or AdoHcy hydrolase but the structure and domain are prevented from binding to MTA phosphorylase and/or AdoHcy hydrolase by at least one domain that is too sterically or electrically hindered to bind to the ribose binding site of MTA phosphorylase or AdoHcy hydrolase.
In another example of a method of the invention, the compound is a selective inhibitor of MTAIAdoHcy nucleosidase if:
i) the compound binds to the 5'-tail binding cavity of MTA/AdoHcy nucleosidase and inhibits MTA/AdoHcy nucleosidase activity and ii) the compound has a structure with at least one domain that would be capable of binding to MTA phosphorylase and/or AdoHcy hydrolase but the structure and domain are prevented from binding to MTA phosphorylase and/or AdoHcy hydrolase by at least one domain that is too sterically hindered to bind to the 5'-tail binding cavity of :20 MTA phosphorylase or AdoHcy hydrolase.
The binding cavity of MTA/AdoHcy nucleosidase optionally comprises amino acids Met9, IIe50, Va1102, Phe105, Pro113, Met173, and Phe207 and (Va1102, Phe105 and Pro113); wherein the residues in the brackets are from a neighbouring monomer;
the amino acids arranged in a spatial relationship represented by the structural coordinates listed in one of Tables 1 to 6;
The binding cavity of MTA phosphorylase optionally comprises amino acids Va1236, Leu237, Va1233, Leu279 and His137 and (Leu279 and His137) wherein the residues in the brackets are from a neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Protein Data Bank Accession No. 1 CG6; and The binding cavity of AdoHcy hydrolase optionally comprises amino acids His55, Cys79, Asn80, Asp131, Asp134, and Leu344; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Protein Data Bank Accession No. 1A7A.
Exploiting the 5' tail binding site The 5'-tail binding cavity is larger in E. coli MTA/AdoHcy nucleosidase than human MTAP because of the deletion of one turn in helix a6 and a shifting of this helix . This truncation and shifting of the helix creates a larger cavity and helps explain the ability of the nucleosidase to bind substrates with bulkier 5'-substiutents, such as AdoHcy.
MTAP prefers binding substrates with smaller 5' tail substituents, such a methylthio group. This difference in substrate and 5' tail binding cavity is exploited by designing bulky substituents to the 5' tail. In the AdoHcy hydrolase structure, based on modeling studies, the homocysteinyl binding site is more restrictive than the nucleosidase's 5'-tail binding site. As well, the hydrolase homocysteine binding site is more hydrophilic as aspartate, asparagine and histidine residues are found in this region, while the nucleosidase binding site is predominantly made up of hydrophobic residues.
The selective inhibition of the MTA/AdoHcy nucleosidase over the AdoHcy hydrolase is optionally attained by introducing a bulky hydrophobic 5' tail group.
Bulkier hydrophobic 5'-substituents improve the binding to the nucteosidase.
The natural substrates, MTA and AdoHcy bind to the nucleosidase with binding constants of K, = 0.5 p.M and 4.3 pM, respectively. The substrate analog, p-2U nitrophenylthioadenosine has a K, = 20 nM [3]. The tighter binding of this compound is likely due to an increase in van der Waals interactions. This shows that the nucleosidase has a preference for 5' substituents that are hydrophobic and bulky.
Exploiting the ribose-binding site The second area where the nucleosidase is optionally exploited is at the ribose-binding site. MTA/AdoHcy nucleosidase has a similar sized ribose-binding site to MTA
phosphorylase but the residues involved in binding are different. These differences explain the inability of the nucleosidase to bind phosphate. In human MTAP, the phosphate interacts with a large number of polar and positively charged residues.
Residues Thr93, Thr197, Arg60, His61, and Thr18 are involved in coordinating the 3U negatively charged phosphate. In the nucleosidase, a cavity similar in size and location to the MTAP phosphate-binding cavity exists. However, the phosphate-binding residues are not present in the nucleosidase and are replaced by more neutral or non-polar residues (GIy75, GIu174, Ser48, and Met9). This cavity binds the nucleophilic water (WAT3). The human AdoHcy hydrolase does not bind phosphate and lacks the phosphate binding cavity all together. The entire ribose-binding site is much smaller than the nucleosidase or the phosphorylase. There is little room to accommodate any substituents at the nucleophilic water binding position.
Inhibitors specific to the nucleosidase can be designed by the addition of a group at the .5 nucleophilic water bindingposition. The addition of a neutral or hydrophobic functional group at the nucleophilic water binding site would complement the electronic nature of the nucleosidase cavity over MTAP and also create steric clashes in the AdoHcy hydrolase ribose-binding site.
The 3-D pdb coordinates of the mamm~ian enzymes can be accessed through the Protein Data Bank at (htta://www.rc,~b.orgl_~~). The pdb accession codes are:
human MTA phosphorylase (MTAP) complexed with MTA and sulfate (1CG6) [27] and human placental AdoHcy hydrolase (1A7A) [21]. The amino acid sequences are in Figure 20.
A candidate compound that is a inhibitor interacts with at least one MTA/AdoHcy nucleosidase residue to inhibit MTA/AdoHcy nucleosidase. "Interact" refers to binding to the enzyme which is capable of modulating its activity. Enzyme fragments may be used in the methods of the invention to predict how the full enzyme will react to a modulator. Since there are two monomers in the asymmetric unit, either may interact with the inhibitor. An inhibitor is capable of changing the enzyme from an open conformation to a closed conformation (or may keep or maintain the enzyme in its open conformation). An inhibitor may bias the enzyme towards a particular conformation instead of (or in addition to) changing the conformation.
A compound of the prlesent invention can be, but is not limited to, at least one selected ftom a nucleic acid, a protein, a lipid, a carbohydrate, a glycoprotein and antibody or fragment thereof, or any combination thereof. Diagnostic compounds (useful in diagnosis or as a research tool in an assay) can be detectably labeled as for labeling antibodies. Such labels include, but are not limited to, enzymatic labels, radioisotope or radioactive compounds or elements, fluorescent compounds or metals, chemiluminescent compounds and bioluminescent compounds. Other types of compounds may also be useful. The compound may include amino acid sequence derivative (i.e. an analog, prepared for example by substituting, deleting, modifying one or more amino acids - see, for example, US Patent Nos. 5,952,297, 5,922,675, 5,700,662, 5,693,609, 5,646,242, 5,149,777, 5,00,8241, 4,946,828 and 5,164,366.
The analog may be an FMA or MTT derivative. One skilled in the art may analyze FMA
or MTT, its precursors, and other known analogs to determine how they interact with enzyme and then prepare improved compounds. Those of skill in the art recognize that a variety of techniques are available for constructing derivatives with the same or similar desired biological activity but with more favorable activity than the FMA or MTT with respect to route of administration, solubility, stability, andlor susceptibility to .5 hydrolysis. Derivatives may be designed on computer by comparing compounds to the 3D structures disclosed in this application. Derivatives of known inhibitors may also be made according to other techniques known in the art. For example, by treating an inhibitor with an agent that chemically afters a side group by converting a hydrogen group to another group such as a hydroxy or amino group.
The amino acid constituents of an MTA/AdoHcy nucleosidase active site, are positioned in three dimensions in accordance with the structure coordinates listed in this application. In one aspect, the structure coordinates defining the active site of MTA/AdoHcy nucleosidase include structure coordinates of all atoms in the constituent amino acids; in another aspect, the structure coordinates of the active site include structure coordinates of just the backbone atoms of the constituent atoms.
The term "MTA/AdoHcy nucleosidase-like binding site" refers to a portion of a molecule or molecular complex whose shape is sufficiently similar to at least a portion of the active site of MTA/AdoHcy nucleosidase as to be expected to bind a structurally related substrate. A structurally equivalent active site is defined by a root mean square deviation from the structure coordinates of the backbone atoms of the amino acids that make up the active site in MTA/AdoHcy nucleosidase of at most about 1.5 A. How this calculation is obtained is described below.
Accordingly, the invention thus provides molecules or molecular complexes comprising an MTA/AdoHcy nucleosidase binding site or an MTA/AdoHcy nucleosidase -like binding site, as defined by the sets of structure coordinates described above.
The term "chemical entity," as used herein, refers to chemical compounds, complexes of two or more chemical compounds, and fragments of such compounds or complexes. Chemical entities that are determined to associate with MTA/AdoHcy nucleosidase are potential drug candidates.
Data stored in a machine-readable storage medium that is capable of displaying a graphical three-dimensional representation of the structure of MTA/AdoHcy nucleosidase or a structurally homologous molecule, as identified herein, or portions thereof may thus be advantageously used for drug discovery. The structure coordinates of the chemical entity are used to generate a three-dimensional image that can be computationally fit to the three-dimensional image of MTA/AdoHcy nucleosidase or a structurally homologous molecule. The three-dimensional molecular structure encoded by the data in the data storage medium can then be computationally evaluated for its ability to associate with chemical entities. When the molecular structures encoded by the data are displayed in a graphical three-dimensional representation on a computer screen, the protein structure can also be visually inspected for potential association with chemical entities.
One embodiment of the method of drug design involves evaluating the potential association of a known chemical entity with MTAIAdoHcy nucleosidase or a structurally homologous molecule, particularly with an MTA/AdoHcy nucleosidase active site or a MTA/AdoHcy nucleosidase-like binding site. The method of drug design thus includes computationally evaluating the potential of a selected chemical entity to associate with any of the molecules or molecular complexes set forth above.
This method comprises the steps of: (a) employing computational means to perform a fitting operation between the selected chemical entity and a binding site, or a pocket nearby the substrate binding site, of the molecule or molecular complex; and (b) analyzing the results of said fitting operation to quantify the association between the chemical entity and the active site.
In another embodiment, the method of drug design involves computer-assisted design of chemical entities that associate with MTA/AdoHcy nucleosidase, its homologs, or portions thereof. Chemical entities can be designed in a step-wise fashion, one fragment at a time, or may be designed as a whole or "de novo."
To be a viable drug candidate, the chemical entity identified or designed according to the method must be capable of structurally associating with at least part of an MTA/AdoHcy nucleosidase or MTA/AdoHcy nucleosidase -like binding sites, and must be able, sterically and energetically, to assume a conformation that allows it to associate with the MTA/AdoHcy nucleosidase or MTA/AdoHcy nucleosidase-like binding site. Non-covalent molecular interactions important in this association include 3.0 hydrogen bonding, van der Waals interactions, hydrophobic interactions, and electrostatic interactions. Conformational considerations include the overall three-dimensional structure and orientation of the chemical entity in relation to the active site, and the spacing between various functional groups of an entity that directly interact with the MTA/AdoHcy nucleosidase -like active site or homologs thereof.

Optionally, the potential binding of a chemical entity to an MTA/AdoHcy nucleosidase or MTA/AdoHcy nucleosidase -like binding site is analyzed using computer modeling techniques prior to the actual synthesis and testing of the chemical entity.
If these computational experiments suggest insufficient interaction and association between it and the MTA/AdoHcy nucleosidase or MTAIAdoHcy nucleosidase -like binding site, testing of the entity is obviated. However, if computer modeling indicates a strong interaction, the molecule may then be synthesized and tested for its ability to bind to or interfere with an MTAIAdoHcy nucleosidase or MTA/AdoHcy nucleosidase -like binding site. Binding assays to determine if a compound actually binds to MTA/AdoHcy nucleosidase can also be performed and are well known in the art. Binding assays may employ kinetic or thermodynamic methodology using a wide variety of techniques including, but not limited to, microcalorimetry, circular dichroism, capillary zone electrophoresis, nuclear magnetic resonance spectroscopy, fluorescence spectroscopy, and combinations thereof.
One skilled in the art may use one of several methods to screen chemical entities or fragments for their ability to associate with an MTA/AdoHcy nucleosidase or MTA/AdoHcy nucleosidase -like active site. This process may begin by visual inspection of, for example, an MTA/AdoHcy nucleosidase or MTA/AdoHcy nucleosidase -like binding site on the computer screen based on the MTA/AdoHcy nucleosidase structure coordinates or other coordinates which define a similar shape generated from the machine-readable storage medium. Selected fragments or chemical entities may then be positioned in a variety of orientations, or docked, within the active site. 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. Examples inGude GRID (P. J. Goodford, J. Med. Chem.
28:849-857 (1985); available from Oxford University, Oxford, UK); MCSS (A. Miranker et al., Proteins: Struct. Funct. Gen.,11:29-34 (1991 ); available from Molecular Simulations, San Diego, Calif.); AUTODOCK (D. S. Goodsell et al., Proteins: Struct. Funct.
Genet.
8:195-202 (1990); available from Scripps Research Institute, La Jolla, Calif.); and DOCK (I. D. Kuntz et al., J. Mol. Biol. 161:269-288 (1982); available from University of California, San Francisco, Calif.).
Once suitable chemical entities or fragments have been selected, they can be assembled into a single compound or complex. Assembly may be preceded 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 MTA/AdoHcy nucleosidase. This could be followed by manual model building using software such as QUANTA or SYBYL (Tripos Associates, St. Louis, Mo.).
Useful programs to aid one of skill in the art in connecting the individual chemical entities or fragments include, without limitation, CAVEAT (P. A. Bartlett et al., in Molecular Recognition in Chemical and Biological Problems," Special Publ., Royal Chem.
Soc., 78:182-196 (1989); G. Lauri et al., J. Comput. Aided Mol. Des. 8:51-66 (1994);
available from the Universihr of California, Berkeley, Calif.); 3D database systems such as ISIS (available from MDL Information Systems, San Leandro, Calif.;
reviewed in Y. C. Martin, J. Med. Cham. 35:2145-2154 (1992)); and HOOK (M. B. Eisen et al., Proteins: Struc. Funct., Genet. 19:199-221 (1994); available from Molecular Simulations, San Diego, Calif.).
MTA/AdoHcy nucleosidase binding compounds may be designed "de novo" using either an empty binding site or optionally including some portions) of a known inhibitor(s). There are many de novo ligand design methods inGuding, without limitation, LUDI (H.-J. Bohm, J. Comp. Aid. Molec. Design. 6:61-78 (1992);
available from Molecular Simulations Inc., San Diego, Calif.); LEGEND (Y. Nishibata et al., Tetrahedron, 47:8985 (1991); available from Molecular Simulations Inc., San Diego, Calif.); LeapFrog (available from Tripos Associates, St. Louis, Mo.); and SPROUT (V.
Gillet et al., J. Comput. Aided Mol. Design 7:127-153 (1993); available from the University of Leeds, UK).
Once a compound has been designed or selecked by the above methods, the efficiency with which that entity may bind to or interfere with an MTA/AdoHcy nucleosidase or MTA/AdoHcy nucleosidase -like binding site may be tested and optimized by computational evaluation. For example, an effective MTA/AdoHcy nucleosidase or MTA/AdoHcy nucleosidase -like binding site inhibitor must preferably demonstrate a relatively small difference in energy between its bound and free states (i.e., a small deformation energy of binding). Thus, the most efficient MTA/AdoHcy nucleosidase or MTA/AdoHcy nucleosidase -like binding site inhibitors should preferably be designed with a deformation energy of binding of not greater than about 10 kcal/mole; more preferably, not greater than 7 kcal/mole. MTAIAdoHcy nucleosidase or MTA/AdoHcy nucleosidase -like binding site inhibitors may interact with the active site in more than one conformation that is similar in overall binding energy. In those cases, the deformation energy of binding is taken to be the difference between the energy of the free entity and the average energy of the conformations observed when the inhibitor binds to the protein.
An entity designed or selected as binding to or interfering with an MTA/AdoHcy nucleosidase or AdoHcy nucleosidase -like binding site may be further computationally optimized so that in its bound state it would preferably lack repulsive electrostatic interaction with the target enzyme and with the surrounding water molecules. Such non-complementary electrostatic interactions include repulsive charge-charge, dipole-dipole, and charge-dipole interactions.
Specific computer software is available in the art to evaluate compound deformation energy and electrostatic interactions. Examples of programs designed for such uses include: Gaussian 94, revision C (M. J. Frisch, Gaussian, Inc., Pittsburgh, Pa. 15106);
AMBER, version 4.1 (P. A. Kollman, University of California at San Francisco, 94143);
QUANTA/CHARMM (Molecular Simulations, Inc., San Diego, Calif. 92121); Insight IIIDisoover (Molecular Simulations, Inc., San Diego, Calif. 92121 ); Delphi (Molecular Simulations, Inc., San Diego, Calif. 92121); and AMSOL (Quantum Chemistry Program Exchange, Indiana University). These programs may be implemented, for instance, using a Silicon Graphics workstation such as an Indigo² with "IMPACT"
graphics.
Other hardware systems and saftware packages will be known to those skilled in the art.
Another approach encompassed by this invention is the computational screening of small molecule databases for chemical entities or compounds that can bind in whole, or in part, to a MTA/AdoHcy nucleosidase or MTAIAdoHcy nucleosidase-like binding site. In this screening, the quality of fit of such entities 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, pp. 505-524 (1992)).
This invention also enables the development of chemical entities that can isomerize to short-lived reaction intermediates in the chemical reaction of a substrate or other compound that interferes with or with MTAlAdoHcy nucleosidase. Time-dependent analysis of structural changes in MTA/AdoHcy nucleosidase during its interaction with other molecules is carried out. The reaction intermediates of MTA/AdoHcy nucleosidase can also be deduced from the reaction product in co-complex with MTA/AdoHcy nucleosidase. Such information is useful to design improved analogs of known MTAIAdoHcy nucleosidase inhibitors or to design novel classes of inhibitors based on the reaction intermediates of the MTA/AdoHcy nucleosidase and inhibitor co-complex. This provides a novel route for designing MTA/AdoHcy nucleosidase inhibitors with both high specificity and stability.
Yet another approach to rational drug design involves probing the MTAlAdoHcy nucleosidase crystal of the invention with molecules comprising a variety of different functional groups to determine optimal sites for interaction between candidate MTA/AdoHcy nucleosidase inhibitors and the protein. 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.
Molecules that bind tightly to those sites can then be further modified and synthesized and tested for their MTA/AdoHcy nucleosidase inhibitor activity (,1. Travis, Science, 262:1374 (1993)).
In a related approach, iterative drug design is used to identify inhibitors of MTA/AdoHcy nucleosidase. Iterative drug design is a method for optimizing associations between a protein and a compound by determining and evaluating the three-dimensional structures of successive sets of protein/compound complexes.
In iterative drug design, crystals of a series of protein/compound complexes are obtained and then the three-dimensional structures of each complex are solved.
Such an approach provides insight into the association between the proteins and compounds of each complex. This is accomplished by selecting compounds with inhibitory activity, obtaining crystals of this new proteinlcompound complex, solving the three dimensional structure of the complex, and comparing the associations between the new proteinlcompound complex and previously solved protein/compound complexes. By observing how changes in the compound affected the protein/compound associations, these associations may be optimized.
A compound that is identified or designed as a result of any of these methods can be obtained (or synthesized) and tested for its biological activity, e.g., inhibition of MTA/AdoHcy nucleosidase activity.
Apparatus including the enzyme 3D structure or other enzyme structural information Storage media for the enzyme 3D structure or other enzyme structural information include, but are not limited to: magnetic storage media, such as floppy discs;
hard disc storage medium, and magnetic tape; optical storage media such as optical discs or CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetiGoptical storage media. Any suitable computer readable mediums can be used to create a manufacture comprising a computer readable medium having recorded on it an amino acid sequence and/or data of the present invention.
"Recorded° refers to a process for storing information on computer readable medium.
5~ A skilled artisan can readily adopt any of the presently know methods for recording information on computer readable medium to store an amino acid sequence, nucleotide sequence andlor EM data information of the present invention.
A variety of data storage structures are available to a skilled artisan for creating a computer readable medium having recorded thereon an amino acid sequence and/or data of the present invention. The choice of the data storage structure will generally be based on the means chosen to access the stored information. In addfion, a variety of data processor programs and formats can be used to store the sequence and data information of the present invention on computer readable medium. The sequence information can be represented in a word processing text file, formatted in commercially-available software such as WordPerfect and Microsoft Word, or represented in the form of an ASCII file, stored in a database application, such as DB2, Sybase, Oracle, or the like. A skilled artisan can readily adapt any number of data processor structuring formats (e.g. text file or database) in order to obtain computer readable medium having recorded thereon the information of the present invention.
By providing the sequence andlor data on computer readable medium and the structural information in this application, a skilled artisan can routinely access the sequence and data to model a enzyme a subdomain thereof, or a ligand thereof.
As described above, computer algorithms are publicly and commercially available which allow a skilled artisan to access this data provided in a computer readable medium and analyze it for molecular modeling or other uses.
The present invention further provides systems, particularly computer-based systems, which contain the sequence and/or data described herein. Such systems are designed to do molecular modeling for an enzyme or at least one subdomain or fragment thereof.
In one embodiment, the system includes a means for producing a 3D structure of MTA/AdoHcy nucleosidase (or a fragment or derivative thereof) and means for displaying the 3D structure of MTA/AdoHcy nucleosidase. The system is capable of carrying out the methods described in this application. The system preferably further includes a means for comparing the structural coordinates of a candidate compound to the structural coordinates of the MTAIAdoHcy nucieosidase (or a fragment or derivative thereof, such an active site or other region described in this application) and means for determining if the candidate compound is capable of modulating MTA/AdoHcy nucleosidase between an open conformation and an closed conformation or biasing MTA/AdoHcy nuGeosidase toward an active or closed conformation, as described in the methods of the invention.
As used herein, "a computer-based system" refers to the hardware means, software means, and data storage means used to analyze the sequence and/or data of the present invention. The minimum hardware means of the computer-based systems of the present invention comprises a central processing unit (CPU), input means, autput means, and data storage means. A skilled artisan can readily appreciate which of the currently available computer-based system are suitable for use in the present invention.
As stated above, the computer-based systems of the present invention comprise a data storage means having stored therein our enzyme or fragment sequence and/or data of the present invention and the necessary hardware means and software means for supporting and implementing an analysis means. As used herein, "data storage means" refers to memory which can store sequence or data (coordinates, distances, 3D structure etc.) of the present invention, or a memory access means which can access manufactures having recorded thereon the sequence or data of the present invention.
As used herein, "search means" or "analysis means" refers to one or more programs which are implemented on the computer-based system to compare a target sequence or target structural motif with the sequence or data stored within the data storage means. Search means are used to identify fragments or regions of an enzyme which match a particular target sequence or target motif. A variety of known algorithms are disclosed publicly and a variety of commercially available software for conducting search means are and can be used in the computer-based systems of the present invention. A skilled artisan can readily recognize that any one of the available algorithms or implementing software packages for conducting computer analyses that can be adapted for use in the present computer-based systems.
As used herein, "a target structural motif," or "target motif," refers to any rationally selected sequence or combination of sequences in which the sequences(s) are chosen based on a three-dimensional configuration or electron density map which is formed upon the folding of the target motif. There are a variety of target motifs known in the art. Protein targets include, but are not limited to, active sites, structural subdomains, epitopes, and functional domains. A variety of structural formats for the input and output means can be used to input and output the information in the computer-based systems of the present invention.
One application of this embodiment provides a block diagram of a computer system that can be used to implement the present invention. The computer system includes a processor connected to a bus. Also connected to the bus are a main memory (preferably implemented as random access memory, RAM) and a variety of secondary storage memory such as a hard drive and a removable storage medium.
The removable medium storage device may represent, for example, a floppy disk drive, A CD-ROM drive, a magnetic tape drive, etc. A removable storage unit (such as a floppy disk, a compact disk, a magnetic tape, etc.) containing control logic and/or data recorded therein may be inserted into the removable medium storage medium.
16 The computer system includes appropriate software for reading the control logic and/or the data from the removable medium storage device once inserted in the removable medium storage device. A monitor can be used as connected to the bus to visualize the structure determination data.
Amino acid, encoding nucleotide or other sequence and/or data of the present invention may be stored in a well known manner in the main memory, any of the secondary storage devices, andlor a removable storage device. Software for accessing and processing the amino acid sequence and/or data (such as search tools, comparing tools, etc.) reside in main memory during execution.
One or mere computer modeling steps and/or computer algorithms are used as 2;5 described above to provide a molecular 3-D model, preferably showing the structure, of a cleaved MTA/AdoHcy nucleosidase, using amino acid sequence data and atomic coordinates for the enzyme. The structure of other MTA/AdoHcy nucleosidases may be readily determined using methods of the invention and the present knowledge of these enzymes.
Accordingly, the invention provides computer media and systems for performing a method of the invention. The invention includes a computer readable media, such as a disk (eg. hard disk, floppy disk, CD-ROM, CD-RW, DVD), with either (a) structural coordinate data according to at least one of Tables 1 to 6 recorded thereon, the data defining the three-dimensional structure of the MTA/AdoHcy nucleosidase, 3;i MTA/AdoHcy nucleosidase bound to an inhibitor, substrate or a fragment of the foregoing, or (b) structure data for the MTA/AdoHcy nucleosidase, MTA/AdoHcy nucleosidase bound to an inhibitor, substrate or a fragment of the foregoing recorded thereon, the structure data being derivable from the structural coordinate data of at least one of Tables 1 to 6.The structural coordinate data is optionally obtained by x-ray diffraction with a crystal of the invention. The data may also be obtained from Protein Data Bank Deposit No. 1 JYS, when available.
Another aspect of the invention relates to a computer system, intended to generate structures and/or perform rational drug design for the MTAIAdoHcy nucleosidase or complexes of the MTA/AdoHcy nucleosidase with an inhibitor or a substrate, the 11) system containing either (a) structural coordinate data according to at least one of Tables 1 to 6, said data defining the 3D structure of MTA/AdoHcy nucleosidase, MTA/AdoHcy nucleosidase bound to an inhibitor, substrate or a fragment of the foregoing, or (b) structure data for MTA/AdoHcy nucleosidase, MTA/AdoHcy nucleosidase bound to an inhibitor, substrate or a fragment of the foregoing, said 1;i structure data being derivable from the atomic coordinate data of at least one of Tables 1 to 6. The structural coordinate data is optionally obtained by x-ray diffraction with a crystal of the invention.
Assays of inhibitors identified from enzyme structure Once identified, the inhbiitor may then be tested for bioactivity using standard 20 techniques (e.g. in vitro or in vivo assays). For example, the compound identified by drug design may be used in binding assays using conventional formats to screen agonists (e.g by measuring in vivo or in vitro binding of enzyme after addition of a compound). Suitable assays include, but are not limited to, the enzyme-linked immunosorbent assay (ELISA), or a fluorescence quench assay. In evaluating 25 enzyme modulators for biological activity in animal models (e.g. rat, mouse, rabbit), various oral and parenteral routes of administration are evaluated.
The method may also further comprise obtaining or synthesizing the compound and determining whether the compound modulates the activity of the MTA/AdoHcy nucleosidase, fragment or derivative in an in vivo or in vitro assay. Such an assay 30 optionally comprises:
a) contacting the compound with an MTA/AdoHcy nucleosidase; and b) measuring the activity of the MTA/AdoHcy nucleosidase; wherein the compound is identified as an compound that inhibits bacterial MTA/AdoHcy nucleosidase when there is a decrease in the activity of the MTAIAdoHcy nucleosidase in the presence of the compound relative to in its absence.
The method may further comprise determining whether the compound inhibits MTA
phosphorylase or AdoHcy hydrolase. MTA/AdoHcy nucleosidase activity is optionally determined by:
a) incubating a test sample comprising MTA/AdoHcy nucleosidase, (ii) the compound;
and (iii) a substrate comprising 5'-methylthioadenosine or S-adenosylhomocysteine;
b) detecting substrate hydrolysis products in the test sample, wherein a decrease in the amount of substrate hydrolysis products in the test sample in the presence of the compound relative to in its absence indicates that the compound is an inhibitor.
The method optionally further comprises:
a) contacting the compound with a MTA phosphorylase or AdoHcy hydrolase; and b) measuring the activity of the MTA phosphorylase or AdoHcy hydrolase;
wherein a compound is identified as an compound for use as an inhibitor of MTA/AdoHcy nucleosidase when MTA/AdoHcy nucleosidase is inhibited and there is no change in the activity of the MTA phosphorylase or AdoHcy hydrolase in the presence of the compound relative to in its absence.
The inhibitor is optionally further characterized by cell based experiments.
One such method involves:
a) contacting the compound with a bacterial culture; and b) measuring the growth of the bacterial culture under conditions in which the bacterial culture grows in the absence of the compound; wherein a potential compound is identified as a compound that inhibits bacterial growth when there is a decrease in the growth of the bacterial culture in the presence of the compound relative to in its absence.
The method optionally further comprises:
a) contacting the compound with a eukaryotic cell; and b) measuring the amount of proliferation of the eukaryotic cell under conditions in which the eukaryotic cell proliferates in the absence of the compound; wherein an compound is identified as an compound for inhibiting bacterial growth when bacterial growth is inhibited and there is no change in the proliferation of the eukaryotic cell in the presence of the compound relative to in its absence.The invention includes a compound obtained according to a method described in this application. The compound used in a method of the invention and thereby identified as an inhibitor :5 optionally comprises a nucleoside. Once identified and screened for biological activity, these inhibitors may be used therapeutically or prophylactically to modulate enzyme activity as described below.
Pharmaceuticalldiagnostic formulations of modulators identified from 3D
structure, methods of medical treatment and uses 1 t) Modulating enzyme in a Cell The present invention also provides a method for inhibiting the activity of the enzyme in a cell using enzyme inhibiting compounds or compositions of the invention.
h general, compounds (antagonists) which have been identified to inhibit the activity of enzyme can be formulated so that the agent can be contacted with a cell expressing 1!5 a enzyme protein in vivo. The contacting of such a cell with such an agent results in the in vivo modulation of the activity of the enzyme proteins. So long as a formulation barrier or toxicity barrier doss not exist, agents identified in the assays described above will be effective for in vivo and in vitro use. These modulators may be used in therapies that are beneficial in the treatment of diabetes and other diseases, 21) disorders and abnormal physical states involving bacteria that have MTA/AdoHcy nucleosidase activity.
Medical Treatments and Uses Microbial organisms, such as bacteria hav~g MTA/AdoHcy nucleosidase cause many diseases in mammals, such as humans. Examples of these bacteria are the folbw ing:
25 Strwtococcus pyrogenes, Yersinia pestis, Vibrio cholerae, Haemophilus influenzae, Ent~ococcus faecalis, Helicobacter pylori, Myccabacterium tuberculosis, Staphylococcus aureus, Streptococcus pneumoniae, Campylobac~r jeji,ni, Treponema pallidum, Borrelia burgdorferi, Salmonella typhimurium~, Escherichia colt, Neisseria meningitides and Bacillus anthracis. Diseases caused by these bacteria 3I) include:
Streptococcus pyrogenes (NP_606713)- pharyngitis (strep throat) scarlet fever impetigo oellulitis Yersinia paella (NP 406846 bubonic plague pneumonic plague brio choleras (NP_232009)- cholera Haemophilus intluenzae (P45113)- pneumonia Enterococcus faecalis- urinary tract infection Helicobacter pylori (024815)- peptic ulcer, gastritis Mycobacterium tuberculosis (Q10888)- tuberculosis 1~0 Staphylococcus aureus (NP_374712)- staphyloenterotoxicosis staphyk~enterotoxemia Streptococcus pneumoniae (NP_358488)- meningitis, pneumonia, infections (eg. ear infections) Campylobacter jsjuni (NP_281328)- campylobacteriosis (gastroenteritis) Treponema pallidum (NP_218608)- syphilis Borrelia burgdorferi (NP_212722)- Lyme disease Salmonella typhimurium (NP_458212)- food poisoning Escherichia coli 0157:H7 (AAC38281)- haemorrhagic colitis Neisseria meningitldis (NP_283757)- meningitis, septicaemia Accession codes are given in the brackets. These bacteria may be killed by administering to a having a bacterial infection a compound that inhibits MTA/AdoHcy nucleosidase. These compounds are preferably selective and inhibit MTA/AdoHcy nucleosidase without affecting mamm~ian enzymes such as MTA
phosphorylase (MTAP) and AdoHcy hydrolase.

Accordingly, the invention includes a method of medical treatment of a microbial disease, preferably bacterial disease, in a subject caused by, for example, a bacteria or microbe such as: Streptococcus pyrogenes, Yersinia pestis, Vibrio cholerae, Haemophilus influenzae, Enferococcus faecalis, Helicobacter pylori, Mycobacterium tuberculosis, Staphylococcus aunsus, Streptococcus pneumoniae, Campylobacter jejuni, Treponema pallidum, Borrelia burgdon'eri, Salmonella typhimurium, Escherichia coli, Neisseria meningitides or Bacillus anfhracis., comprising administering to the subject a compound identified by a method of the invention. The invention also includes the use of the compound of the invention for treatment of a microbial disease, preferably bacterial disease, caused by bacteria selected from the group consisting of: Strr~ptococcus pyrogenes, Yersinia pestis, Vibrio cholerae, Haemophilus influenzae, Enterococcus faecalis, Helicobacter pylori, Mycobacterium tuberculosis, Staphylococcus aureus, Streptococcus pneumoniae, Campylobacter jejuni, Treponema pallidum, Borrelia burgdorferi, Salmonella typhimurium, Escherichia coli, Neisseria meningitides and Bacillus anthracis and any microbe, preferably bacteria, having MTA/AdoHcy nucleosidase.Te disease includes a disease selected from the group consisting of pharyngitis, scarlet fever, impetigo cellulites, bubonic plague, pneumonic plague, cholera pneumonia urinary tract infection peptic ulcer, gastritis, tuberculosis, staphyloenterotoxicosis, staphyloenterotoxemia, meningitis, pneumonia, infections campylobacteriosis, syphilis, Lyme disease, food poisoning, haemorrhagic colitis, meningitis and septicaemia.
Pharmaceutical Compositions Inhibitors may be combined in pharmaceutical compositions according to known techniques. The compounds of this invention are preferably incorporated into pharmaceutical dosage forms suitable for the desired administration route such as tablets, dragees, capsules, granules, suppositories, solutions, suspensions and lyophilized compositions to be diluted to obtain injectable liquids. The dosage forms are prepared by conventional techniques and in addition to the compounds of this invention could contain solid or liquid inert diluents and carriers and pharmaceutically useful additives such as lipid vesicles liposomes, aggregants, disaggregants, salts for regulating the osmotic pressure, buffers, sweeteners and colouring agents.
Slow release pharmaceutical forms for oral use may be prepared according to conventional techniques. Other pharmaceutical formulations are described for example in US
5,192,746.
3.5 Pharmaceutical compositions used to treat patients having diseases, disorders or abnormal physical states could include a compound of the invention and an acceptable vehicle or excipient (Remington's Pharmaceutical Sciences 18th ed, (1990, Mack Publishing Company) and subsequent editions). Vehicles include saline and D5V11 (5% dextrose and water). Excipients include additives such as a buffer, solubilizer, suspending agent, emulsifying agent, viscosity controlling agent, flavor, lactose filler, antioxidant, preservative or dye. The compound may be formulated in solid or semisolid form, for example pills, tablets, creams, ointments, powders, emulsions, gelatin capsules, capsules, suppositories, gels or membranes.
Routes of administration include oral, topical, rectal, parenteral (injectable), local, inhalant and epidural administration. The compositions of the invention may also be conjugated to transport molecules to facilitate transport of the molecules. The methods for the preparation of pharmaceutically acceptable compositions which can be administered to patients are known in the art.
The pharmaceutical compositions can be administered to humans or animals.
Dosages to be administered depend on individual patient condition, indication of the drug, physical and chemical stability of the drug, toxicity, the desired effect and on the chosen route of administration (Robert Rakel, ed., Conn's Current Therapy (1995, W.B. Saunders Company, USA)).
Materials and Methods re Crystallization of the Adenine-bound E. coli MTAIAdoHcy nucleosidase Expression and Purification An EcoRIINotI fragment from p5Xmtan (Cornell & Riscoe, 1998) containing the complete E. coli MTA/AdoHcy nucleosidase gene (accession #U24438) was ligated into EcoRl/Notl digested pPROEX HTa expression vector (Gibco BRL) and transformed into E. coli strain TOP10F (F'{laclq,Tn10[Tet']}mcrA~(mrr-nsoIRMS-mcrBC) ~801acZOM1501acx74 deoR recA1araD1390[ara-leu)7697gaN galK rpsL[strR] endA1 nupG). The expressed enzyme contains a 31 residue N-terminal fusion consisting of a 6-histidine tag, spacer sequence and a rTEV protease cleavage site prior to the native initiating methionine of the nucleosidase. A starter culture of 10 mL
LB with 100Ng/ml ampicillin was inoculated with a single transformed colony and grown overnight at 37 °C in a water bath shaker (200rpm). This overnight culture was added to 1 L of LB media containing 100 Ng/ml ampiallin and incubated at 37 °C in a water bath shaker (200rpm) until an ODs reading of 0.7. At which point, protein expression was induced by IPTG to a final concentration of 1 mM. The cells were harvested 3 hours post-induction by centrifugation (5000rpm, Beckman JA-10 rotor, 4 °C, 10 minutes) and resuspended in 40m1 B-PER (Pierce) containing a protease inhibitor cocktail tablet (Boehringer-Mannheim). The cells were lysed by gentle vortexing at room temperature (22 °C) for 10 minutes. The cell debris were removed by centrifugation at 12,OOOrpm for 20 minutes in a Beckman JA-20 rotor. The supernatant was directly applied to a 5 mL Ni-NTA (Qiagen) column pre-equilibrated in Buffer A (50 mM sodium phosphate pH 7.5) with 20 mM imidazole. The column was subsequently washed with 25 mL of Buffer A plus 20 mM imidazole and the protein eluted from the column in a single 15 mL fraction of Buffer A with 250 mM
imidazole.
The protein was subsequently dialyzed against 1 L of Buffer A overnight at 4 °C.
Since attempts to crystallize the N-terminally His-tagged protein failed and cleaving the His-tag using rTEV resulted in the protein precipitating, limited proteolysis was used to find a smaller protein fragment that was more suitable for crystallographic study.
MTA/AdoHcy nucleosidase was incubated with chymotrypsin (1:1000 molar ratio of chymotrypsin to protein) at room temperature (22°C). After 1 hour, the reaction was stopped with the addition of PMSF to a final concentration of 1mM. The resulting reaction mixture (15 mL) was reapplied to a 5 mL Ni-NTA column pre-equAibrated in Buffer A to remove the N-terminal fragment and any unproteolyzed protein. The flow through was collected and EDTA was immediately added to a final concentration of 1 mM to bind any leached nickel. The protein was concentrated to approximately 2 mL
using an Ultrafree-15 BioMax-10K (Millipore) centrifuge concentrator prior to application on a gel-filtration column. MTA/AdoHcy nucleosidase was applied in 0.5 mL fractions to a Superdex-75HR FPLC column pre-equilibrated with 50 mM sodium I-EPES pH 7.5 and isocratically eluted at a flow rate of 0.5 mUmin. Fractions were pooled according to the chromatogram and concentrated to 15mglml in an Ultrafree-0.5 BioMax-10K micro-concentrator. This preparafion of enzyme was then subsequently used in crystallization trials.
Protein purity was assessed using SDS-PAGE stained with Coomassie blue (Fig.
1).
From 1 L of bacterial culture, approximately 30mg of ~99°l°
pure, soluble protein was obtained. The concentrations of MTA/AdoHcy nucleosidase were measured using the Coomassie Plus (Pierce) protein determination method (Bradford, 1976).
Analysis 3.0 of the proteolytic fragment using N-terminal amino acid sequencing revealed that in addition to the 6-histidine tag, 11 amino acids located in the N-terminal spacer region were cleaved (Fig. 2). A total of 21 residues were proteolyzed from the N
terminal region. The molecular weight of the protein, determined by electrospray mass spectrometry (25,464 Da) confirmed that no other residues had been excised.
Crystallization Initial screening for crystallization conditions was performed using commercially purchased sparse-matrix screens (Jancarik 8~ Kim, 1991) from Hampton Research (Crystal Screen I and II) and Emerald Biostructures {Wizard I and II). Two different crystallization conditions of E. coli MTA/AdoHcy nucleosidase were obtained.
At present, only one of these conditions (Condition 2) has yielded crystals suitable far X-ray diffraction studies. All crystals were grown using the hanging-drop vapour-diffusion technique by mixing 2N1 of protein (15mg/mL) in 50mM sodium HEPES pH
7.5 with 1 NL of precipitating solution on a siliconized coverslide and equilibrated against 1.0 mL of the same precipitant solution. Crystals were grown in an incubator maintained at 20°C. Condition 9: Microcrystals were obtained overnight from 4.0 M
sodium formate. Larger hexagonal disc-like crystals (0.4 x 0.4 x 0.1 mm) were grown by lowering the precipitant concentration to 3.2M sodium formate and adding 50 mM
guanidine-hydrochloride. When irradiated with X-rays, these crystals diffracted to 6 A. Condition 2: Small rod-like microcrystals were obtained within 2 days from 1.0 M
sodium citrate, 100 mM CHES pH 9.5. Optimization of this condition (0.72-0.77 M
sodium citrate, 100 mM CHES pH 8.5, 0.8 mM CHAPS) produced diamond-shaped crystals (0.6 x 0.2 x 0.1 mm) within 5-7 days (Fig. 3).
X ray Data Collection and Analysis Prior to data collection, a crystal (0.4 x 0.2 x 0.1 mm) was transferred to a cryoprotectant solution containing 15% {w/v) glucose, 0.9 M sodium citrate, 100 rrilA
CHES pH 8.5 for 2 minutes. The crystal was subsequently transferred to a 30%
(w/v) glucose, 0.9 M sodium citrate, 100 mM CHES pH 8.5 solution for an additional 2 minutes prior to being cooled in a stream of nitrogen gas (-173°C).
Data were collected using a MAR345 image plate with a Rigaku RU200 rotating anode X-ray generator. A total of 244 frames of 1 °-_~ oscillations were collected.
The crystals diffracted to a minimum d spacing of 2.3 A.
Preliminary autoindexing, refinement of the cell and setting parameters and the data processing were performed using the HKL data processing suite (Otwinowski &
Minor, 1997). The unit cell dimensions were found to be a = 50.92A, b =
133.99A, c =
70.88A, a=~i=r= 90°. The full data reduction statistics are presented in Table 7.
Examination of the systematic absences uniquely determined the space group to be P2,2,2.
SeMet protein preparation, crystaNization, and data coNection E. coli MTA/AdoHcy nucleosidase expression and purification was described previously (18]. Selenocysteine or selenomethionine may be incorporated into wild-type or mutant MTA/AdoHcy nucleosidase by expression of MTA/AdoHcy nucleosidase-encoding cDNAs in auxotrophic E. coli strains (W. A Hendrickson et al., EMBO J., 9(5):1665-1672 (1990)). In this method, the wild-type or mutagenized MTA/AdoHcy nucleosidase cDNA may be expressed in a host organism on a growth median depleted of either natural cysteine or methionine (or both) but enriched in selenocysteine or selenomethionine (or both). Alternatively, selenomethionine analogues may be prepared by down regulation methionine biosynthesis. (T. E
Benson et al., Nat. Struct. Biol., 2:644-53 (1995); G. D. Van Duyne et al., J.
Mol. Biol.
229:105-24 (1993)). The following modifications were made for the expression of the selenomethionyl incorporated protein. The cell line was changed from TOP10 F' to the 8834 Met E. coli auxotroph (Novagen, Inc) so that selenomethionine could be incorporated into the protein and the expression media was changed to M9 salts supplemented with 40 Ng/mL L-amino acid (all amino acids except L-methionine), 0.4%
(w/v) glucose, 2 mM MgS04, 25 pg/mL FeS04.7H20, 1 Ng/mL riboflavin, 1 frg/mL
niacinamide, 1 NgImL pyradoxine monohydrochloride, 1 Ng/mL thiamine, 100 Ng/mL
ampicillin, and 60 pg/mL D/L-seienomethionine. LB cultures were inoculated with cells from a 10 mL overnight LB starter culture. All buffers used in the purfication also contained 0.5 mM TCEP (Hampton Research) and 1 mM EDTA to prevent oxidation of the selenium. Crystals of SeMet MTA/AdoHcy nucleosidase were grown at 20 °C
using the hanging drop vapour diffusion technique as described previously [18].
Crystals were grown from 15 mglmL MTAIAdoHcy nucleosidase in 0.7 M sodium citrate, 100 mM (~-IES pH 8.5, and 0.8 mM CHAPS detergent. Diffraction quality crystals (0.6 mm x 0.2 mm x 0.2 mm) were grown in about 5-7 days. In preparation for data collection at liquid nitrogen temperatures, the crystals were soaked in 15%
(w/v) glucose, 0.7 M sodium citrate, 100 mM CHES pH 8.5 for two minutes then subsequently soaked in a cryoprotectant with a higher concentration of glucose (30%
w/v glucose, 0.7 mM sodium citrate, 100 mM CHES pH 8.5) for an additional 2 minutes prior to flash freezing.
Multiwavelength anomalous diffraction data were coltected on a single SeMet crystal at 100K on Beamline XBC, National Synchrotron Light Source (Brookhaven National Laboratories, Upton, NY). The data were collected to 2.05 A resolution on a Quantum-4 CCD detector. A total of 720, - 0.5° oscillation frames were collected at each of the three wavelengths in a continuous wedge. The data were processed using the HKL data processing suite [39]. The SeMet crystals are isomorphous with the native crystals (P2~2~2, a = 50.7 A, b = 133.4 A, c = 70.9 A, a=~=X900°) and contain two monomers in the asymmetric unit.
____._ ~_~____._ .""~""~",~"~"", ._-~w.____ Adenine-bound E. coli MTA/AdoHcy nucleosidase crystals were grown as previously described (18]. A 1.90 A resolution dataset was measured on a single crystal (100 K) at the Hospital for Sick Children using monochromated CuKa X-ray radiation (RU-H3R rotating anode X-ray generator) on a Rigaku R AXIS IV+'"
image plate. The data were indexed, integrated and scaled using the d*trek data processing suite [40]. Data collection statistics for the MAD and native data are presented in Table 8.
Structure determination, model building and refinement The program CNS (41] was used far all stages of the structure determination and refinement. The atomic positions of the selenium atoms were found using anomalous difference Patterson maps and the peak) wavelength data [42]. The selenium atom positions were refined and the MAD data phased as a speaal case of multiple isomorphous replacement to 2.4 A resolution [43]. The initial solvent-flattened MAD
map showed clear solvent boundaries and continuous electron density (Figure 4a).
The interactive computer graphics program Xfit in the XtalView crystallography program suite [44] was used to build the initial Ca trace of a MTA/AdoHcy nucleosidase monomer. A total of 227 Ca atoms were built into the initial map.
Using 2C1 the selenium sites as reference points for fitting the sequence, mainchain and sidechain atoms were inserted. The electron density for residues -10 to -1 (N-terminal fusion tag), 201-205 and the C-terminal residues 231-232 was poor in each monomer and these residues were therefore omitted from the model. The initial model was refined against the 2.4 A resolution SeMet data using CNS (41]. Rounds of simulated annealing (SA) using torsion angle dynamics [45], were alternated with manual refitting of the model using NCS averaged, aA weighted Fa F~, and 2Fo F
electron density maps. The final 2.4 A resolution model consisted of residues 1-201, and 205-230.
30~ The 2.4 A resolution SeMet MTA/AdoHcy nucleosidase model was subsequently used to phase and refine the native 1.90 A resolution data. This higher resolution data allowed for minor adjustments to many main chain and sidechain positions and significant changes to residues 206-210. Rounds of simulated annealing using torsion angle dynamics in the resolution range 50-1.9 A with no sigma cutoff and a bulk solvent correction applied to the data were alternated with manual rebuilding in Xfit.
The progress of the refinement was monitored by reductions in the R~~~ and R,,,B.
Water molecules were included in the model during the later rounds of the refinement based on the presence of a 3a peak in the Fo F~ difference map and at least one hydrogen bond to a protein, ligand or solvent atom. In the active site, strong planar density was observed in the Fo-Fc difference maps. In the final rounds of refinement, this planar density was modeled as an adenine ligand (Figure 4b).
The final model includes 215 water molecules, 20 ligand atoms, and 3318 protein atoms from 227 of the 232 MTA/AdoHcy nucleosidase residues. Analysis of the structure in PROCHECK [46, 47] reveals that none of the non-glycine residues fall into the disallowed region of the Ramachandran plot. A summary of the refinement statistics is presented in Table 9.
Structure-based sequence alignment A structural alignment of MTA/AdoHcy nucleosidase with E. coli PfW (1ECP), and human MTA phosphorylase (1CG6) was performed by submitting the three-dimensional coordinates of each model to the TOP server (http://bioinfo1.mbfys.lu.seITOP). The resulting PDB superimposition file was verified by graphically viewing the moc~l in Setor [48]. Based on the structural superimpositions, a sequence alignment was generated using the program BioEdit.
Materials and Methods re Co-crystallttation with FMA and MTT
Protein Preparation and Crystallization Soaking experiments were initially used to generate the inhibitor-nucleosidase complexes. Crystals grown from 0.7 M sodium citrate, 100 mM CHES pH 8.5, and 0.8 mM CHAPS were transferred to a drop of pseudo-mother liquor containing inhibitor.
The crystals however immediately cracked and disintegrated. Screening for alternative conditions was therefore initiated. The purified protein was concentrated to 15 mg/ml and incubated with 1 mM FMA or 1 mM MTT on ice for 2 hours. Rod-shaped crystals (0.15 mm x 0.15 mm x 1.0 mm) were grown at room temperature using the hanging drop vapour diffusion technique over a three week period (37%
(w/v) PEG 200, 100 mM sodium acetate pH 4.7, 100 mM NaCI, and 8.0 mM cobaltous chloride).
Data collection and processing The FMA and MTT-nucleosidase co-crystals were frozen without use of further cryo-protectant in a stream of nitrogen gas (100K). Data for the nucleosidase-FMA
complex were collected on a R-AXIS-IV'+ image plate and RUH3R rotating anode X-ray generator with Osmic optics. Data for the MTT containing crystal were collected at Station X8C at the National Synchrotron Light Source (NSLS, Brookhaven National Laboratories). All data were processed using the program d*trek . The data collection statistics are presented in Table 10.
Structure determination and refinement The structure of the FMA-complexed nucleosidase was determined using the molecular replacement technique and the structure of E. coli MTA/AdoHcy nucleosidase complexed with adenine (PDB code: 1JYS) as the search model. The program CNS was used for all structure determination and refinement steps.
Data between 12 and 5 A resolution were included in the cross-rotation and translation functions. The resulting model was then refined using torsion angle simulated annealing. The interactive computer graphics program Xfit in the XtaIView crystallographic suite was used to rebuild the initial model in the FMA-containing structures. Several rounds of torsion angle simulated annealing starting at using all data with no a cutoff and a bulk solvent correction were alternated with manual rebuilding in Xfit. The progress of the refinement was monitored by reductions in R~,~,Bt and R,,~ factors. Difference Fourier maps calculated after the initial round of simulated annealing revealed strong positive electron density corresponding to FMA in the two active sites. The FMA coordinates were generated by modifying the PDB file of adenosine downloaded from the HIC-UP server. The topology and parameter files for FMA were generated using the XPL02D server.
Water molecules were included into the model during the later rounds of the refinement based on the presence of a 3a peak in the aA weighted Fo-Fc difference electron density maps and at least one hydrogen bond to a protein, inhibitor, or solvent atom. After the addition of the inhibitor and water molecules, alternating rounds of crystallographic conjugate gradient minimization refinement and model rebuilding in Xfit was performed.
30i The MTT-complexed structure was solved using molecular replacement with the FMA-complexed structure. Data between 12 and 4 A resolution were included in the cross-rotation and translation functions. The resulting search model was carried through a round of rigid-body refinement using all data between 35-2.0 A in CNS. aA-35~ weighted difference and 2Fo F~ Fourier maps were calculated and the model was rebuilt using X6t. The model was subsequently refined using torsion angle simulated annealing and conjugate gradient minimization refinement. The MTT inhibitor was visible as the largest peak in the difference Fourier maps. The MTT molecule was generated by modifying the coordinates of the MTA ligand found in the MTA
phosphorylase structure. The topology and parameter files were generated using the XPL02D server. Water molecules were included into the model as described above in the FMA-complexed structure. Analysis of both structures using PROCHECK reveal that none of the nonglycine residues fall into the disallowed region of the Ramachandran plot. The refinement statistics for the structures are reported in Table 7.
Superimposition of structures The MTA/AdoHcy nucleosidase were aligned by non-linear least-squares fit of selected mainchain (N-Ca-C) atoms in the central ~i-sheet using the program PROh~T
(written by G. David Smith). The residue ranges used in the refinement of the superposition are Lys2-Ile6, G1u42-Leu46, Leu62-A1a77, Va190-Arg96, Pro116-A1a121, and Va1187-Va1191.
Materials and Methods re Crystallization of S. pneumoniae complexed with 8-aminoadenine Expression and purification An N-terminally 6-His tagged, full length S. pneumoniae MTAIAdoHcy nucleosidase was cloned into Nde/Xho digested pET 28a expression vector (Novagen). The expressed enzyme contains a 21 residue N-terminal fusion tag consisting of a 6-histidine tag, and a spacer sequence. The expression vector was transformed into BL21 (DE3) cells and a single colony was used to start an overnight culture of 50 mL
LB broth containing 100 wM kanamycin. This overnight culture was used to inoculate 1.6 L LB containing 100 p.M kanamycin and grown to an absorbance (600nm) of 0.6 at 37 °C. Expression was induced by addition of IPTG to 400 pM. Cells were allowed to grow for an additional 3 hours with a temperature shift to 27 °C. The induced culture was harvested by post-induction by centrifugation (6000 rpm, Beckman JA-10 rotor, 10 minutes). The cells were resuspended in 40 mL of BugBuster protein extraction reagent (Novagen) and lysed by gentle vortexing at room temperature for 20 minutes.
The cell debris were removed by centrifugation at 12,000 rpm for 20 minutes in a Beckman JA-20 rotor. The supernatant was directly applied to a 10 mL Ni-NTA
superfolw (Qiagen) column prequilibrated in Buffer A (50 mM sodium phosphate pH
7.5 with 20 mM imidazole). The column was subsequently washed with 2 column volumes of Buffer A and the protein was eluted in 30 mL of Buffer A with 500 mM
imidazole. The protein was subsequently dialyzed against 1 L of Buffer A
overnight at 4 °C. The, N-terminal fusion tag was cleaved using trypsin. The enzyme was 4CI incubated with chymotrypsin (1:1000 molar ratio of trypsin to protein) at room temperature for 1 hour. After 1 hour, the reaction was stopped with the addition of PMSF to a final concentration of 1 mM. The protein was concentrated to ~2 mL
using an Ultrafree-15 BioMax-10K (Millipore) centrifuge concentrator prior to application on a gel-filtration column. MTA/AdoHcy nucleosidase was applied in 0.5 mL fractions to a Superdex-200 HR FPLC column pre-equilibrated with 25 mM sodium HEPES pH 7.5 and isocratically eluted at a flow rate of 0.5 mUmin. Fractions were pooled according to the chromatogram and concentrated to 15 mg/mL. The substrate analog 8-aminoadenosine was incubated with the protein at a final concentration of 1.5 mM for 2 hours at room temperature. This preparation of enzyme was then subsequently used in crystallization trials.
Crystallization Initial screening for crystallization conditions was performed using commercially purchased sparse-matrix screens (Jancarik 8~ Kim, 1991 ) from Hampton Research (Crystal Screen I and II, and Cryo) and Emerald Biostructures (Wizard I and II, Cryo I
and II). All crystals were grown using the hanging-drop vapour-diffusion technique by mixing 2 wL of protein (15mgimL) in 25mM sodium HEPES pH 7.5 with 1 wl of precipitating solution on a siliconized coverslide and equilibrated against 1.0 mL of the 20~ same precipitant solution. Crystals were grown at roam temperature. One of the conditions from Hampton Screen Cryo (condition 38) yielded crystals suitable for X-ray diffraction studies. The reservoir in condtion 38 contained 1.26 M sodium citrate, 90 mM sodium HEPES pH 7.5, and 10 % glycerol. The crystals grew as cube to ~0.3 x 0.3 x 0.3 mm in size within 2-3 days.
Data collection and processing The S. pneumoniae nucleosidase crystals were frozen without use of further cryo-protectant in a stream of nitrogen gas (-180 °C). The crystals were diffracted on a R-AXIS-IV'~ image plate and RUH3R rotating anode X-ray generator with 4smic optics.
The crystal diffracts to 1.6 A resolution in the space group 14,32 with a unit cell a=145.7 A, b=145.7 A, and c=145.7 A, a=~.--y= 90° . There is only one molecule in the asymmetric unit. All data were processed using the program d*trek.
Structure determination and refinement The structure of the S. pneumoniae nucleosidase complexed with 8-aminoadenosine was determined using the molecular replacement technique and the structure of E.
coli MTA/AdoHcy nucleosidase complexed with MTT as the search model. The program CNS was used for all structure determination and refinement steps.
Data between 12 and 5 A resolution were included in the cross rotation and translation functions. The resulting model was then refined using rigid-body refinement.
The computer graphics program Xfit was used to rebuild the initial model. Several rounds of torsion angle simulated annealing starting at 5000 K using all data with no 6-cutoff and a bulk solvent correction were alternated with manual rebuilding in Xfit.
The progress of the refinement was monitored by reductions in Rat and R~ factors.
Difference Fourier maps calculated after the initial round of simulated annealing revealed strong positive electron density corresponding to 8-aminoadenine in the active site. The 8-aminoadenine coordinates were generated by modifying the PDB
file of adenine downloaded from the HIC-UP server. The topology and parameter files for 8-aminoadenine were generated using the XPL02D server. Water molecules were included into the model during the later rounds of the refinement based on the presence of a 3Q peak in the aA-weighted Fo F~ difference electron density maps and at least one hydrogen bond to a protein, inhibitor, or solvent atom. After the addition of the inhibitor and water molecules, alternating rounds of crystallographic conjugate gradient minimization refinement and model rebuilding in Xfit was performed.
Matsris~ls and Methods re Crystallization of S, aursus complsxed to FormycinA
Expression and purification An N-terminally 6-His tagged, full length S. aureus MTA/AdoHcy nucleosidase was cloned into Ndel/Xhol digested pET 28a expression vector (Novagen). The expressed enzyme contains a 21 residue N-terminal fusion tag consisting of a 6-histidine tag, and a spacer sequence. The expression vector was transformed into BL21 (DE3) cells and a single colony was used to start an overnight culture of 50 mL LB broth containing 100 pM kanamycin. This overnight culture was used to inoculate 1.6 L LB
containing 100 pM kanamycin and grown to an absorbance (600nm) of 0.6 at 37 °C.
Expression was induced by addition of IPTG to 400 p,M. Cells were allowed to grow for an additional 3 hours with a temperature shift to 27 °C. The induced culture was harvested by post-induction by centrifugation (6000 rpm, Beckman JA-10 rotor, minutes). The cells were resuspended in 40 mL of BugBuster protein extraction reagent (Novagen) and lysed by gentle vortexing at room temperature for 20 minutes.
The cell debris were removed by centrifugation at 12,000 rpm for 20 minutes in a Beckman JA-20 rotor. The supernatant was directly applied to a 10 mL Ni-NTA
superfolw (Qiagen) column prequilibrated in Buffer A (50 mM sodium phosphate pH
7.5 with 20 mM imidazole). The column was subsequently washed with 2 column volumes of Buffer A and the protein was eluted in 30 mL of Buffer A with 500 mM
imidazole. The protein was subsequently dialyzed against 1 L of Buffer A
overnight at 4 °C. The N-terminal fusion tag was cleaved using chymotrypsin. The enzyme was incubated with trypsin (1:1000 molar ratio of trypsin to protein) at room temperature ,5 for 1 hour. After 1 hour, the reaction was stopped with the addition of PMSF to a final concentration of 1 mM. The protein was concentrated to ~2 mL using an Ultrafnre-15 BioMax-1 OK (Millipore) centrifuge concentrator prior to application on a gel-filtration column. MTA/AdoHcy nucleosidase was applied in 0.5 mL fractions to a Superdex-200 HR FPLC column pre-equilibrated with 25 mM sodium HEPES pH 7.5 and isocratically eluted at a flow rate of 0.5 mUmin. Fractions were pooled according to the chromatogram and concentrated to 15 mg/mL. The transition state inhibitor Formycin A was incubated with the protein at a final concentration of 1.5 mM
for 2 hours at room temperature. This preparation of enzyme was then subsequently used in crystallization trials.
Crystallization Initial screening for crystallization conditions was performed using commercially purchased sparse-matrix screens (Jancarik & Kim, 1991) from Hampton Research (Crystal Screen I and II, and Cryo) and Emerald Biostructures (Wizard I and II, Cryo I
and II). All crystals were grown using the hanging-drop vapour-diffusion technique by mixing ZN.L of protein (15mgImL) in 25mM sodium HEPES pH 7.5 with 1p,L of precipitating solution on a siliconized coverslide and equilibrated against 1.0 mL of the same precipitant solution. Crystals were grown at room temperature. One of the conditions from Hampton Screen I (condition 42) yielded crystals suitable for X-ray diffraction studies. The reservoir in condtion 42 contained 20°10 (w/v) PEG 8000, and 50 mM potassium phosphate. The crystals grew as cube to ~0.3 x 0.3 x 0.3 mm in size within 2-3 days.
Data collection and processing The S. aureus nucleosidase crystals were first soaked in a cryo-protectant of 20%
PEG 8000, 50 mM potassium phos~ate, 1.5 mM Formycin A, and 1596 glycerol for 2 minutes. The crystal was subsequently soaked in a 20% PEG 8000, 50 mM
potassium phosphate, 1.5 mM Formcyin A, and 30% glycerol for another 2 minutes prior to being cooled in a stream of nitrogen gas (-180 °C). The crystals were diffracted on a R-AXIS-IV'''' image plate and RU H3R rotating anode X-ray ger~rator with Osmic optics.
The crystal diffracts to 1.9 A resolution in the space group P2,2~2 with a unit cell a=58.3 A, b=81.7 A, and c=45.5 A, a=~--~y=90°. There is only one molecule in the asymmetric unit. All data were processed using the program d*trek.
Structure determination and refinement The structure of the S. aureus nucleosidase complexed with Fonnycin A was determined using the molecular replacement technique and the structure of E.
coli MTA/AdoHcy nucleosidase complexed with MTT as the search model. The program CNS was used for all structure determination and refinement steps. Data between 12 and 5 A resolution were inGuded in the cross rotation and translation functions. The resulting model was then refined using rigid-body refinement. The computer graphics program Xfit was used to rebuild the initial model. Several rounds of torsion angle simulated annealing starting at 5000 K using all data with no a-cutoff and a bulk solvent correction were alternated with manual rebuilding in Xfit. The progress of the refinement was monitored by reductions in R~,st and Rfr~ factors. Difference Fourier maps calculated after the initial round of simulated annealing revealed strong positive electron density corresponding to Formycin A in the active site. Water molecules were included into the model during the later rounds of the refinement based on the presence of a 3a peak in the aA-weighted Fo F~ difference electron density maps and at least one hydrogen bond to a protein, inhibitor, or solvent atom. After the addition of the inhibitor and water molecules, alternating rounds of crystallographic conjugate gradient minimization refinement and model rebuilding in Xfit was performed.
Materials and Methods re Crystallization of E. cola MTAIAdoHcy nucieosidase E12A mutant complexed to AdoHcy Site-directed mutagenesis, expression, purification, crystallization The QuikChange site directed mutagenesis kit (Strategene) was used to generate the E12A mutant of MTAlAdoHcy nucleosidase. The wild type MTA/AdoHcy nucleosidase gene in the pPROEX HTa expression vector (Life Technologies) was used as a template for the mutagenesis reaction. The oligonucleotides, 5'-GCAATGGAAGAAGCGGTTACCCTGCTGCGTGAC-3' and 3'-GTCACGCAGCAGGGTAACCGCTTCTTCCATTGC-5' were designed and synthesized.
The site directed mutagenesis PCR reaction was pertormed according to the protocol provided with the QuikChange kit. The mutant cDNA was transformed into XL1-Blue supercompetent cells and plated on an LB-ampicillin agar plate. Selection of positive mutants was performed by DNA sequencing. The E12A mutant was expressed, and purified in the same manner as previously described.

The natural substrate AdoHcy was incubated with the purified E12A nucleosidase enzyme to a final concentration of 1 mM on ice for 2 hours. Co-crystals of AdoHcy and the nucleosidase were obtained in a crystallization range of 37%-55% (w/v) PEG
200, 100 mM sodium acetate pH 4.7, 100 mM NaCI, 10 mM CoC12.6H20, and 1 mM
AdoHcy.
Data collection and processing The AdoHcy-bound E12A nucleosidase crystal was frozen without use of further cryo-protectant in a stream of nitrogen gas (-180 °C). The crystals were diffracted on a R-AXIS-IV++ image plate and RU H3R rotating anode X-ray generator wkh Osmic optics. The crystal diffracts to 2.2 A resolution in the space group P2,2,2~
with a unit cell a=52.0 A, b=69.0 A, and c=128.1 A, a=[3--y= 90°. There are two molecules in the asymmetric unit. All data were processed using the program d*trek.
Structure determination and refinement Crystals of the E12A AdoHcy-bound and MTT-bound nucleosidase complexes were essentially isomorphous allowing for solution by a difference Fourier method.
Rigid-body refinement was initially performed to optimize the positioning of the nucleosidase molecules. Several rounds of torsion angle simulated annealing starting at using all data with no a-cutoff and a bulk solvent correction were alternated with manual rebuilding in Xfit. The progress of the refinement was monitored by reductions in R~~,at and R,~ factors. Difference Fourier maps calculated after the initial round of simulated annealing revealed strong positive electron density corresponding to AdoHcy in the active site. Water molecules were included into the model during the later rounds of the refinement based on the presence of a 3a peak in the aA weighted Fo F~ difference electron density maps and at least one hydrogen bond to a protein, substrate, or solvent atom.
The present invention has been described in detail and with particular reference to the preferred embodiments; however, it will be understood by one having ordinary skill in the art that changes can be made thereto without departing from the spirit and scope thereof.
All publications (including database entries), patents and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety.

References re Background of invention and Crystallization of E. coli MTA/AdoHcy nucleosidase:
Backlund, P. J. & Smith, R. A. (1981). J. Biol. Chem. 256, 1533-1535.
Backlund, P. J. & Smith, R. A. (1982). Biochem. Biophys. Res. Common. 108, 687-695.
Bradford, M. (1976). Anal. Biochem. 72, 248-254.
Cornell, K. A. & Riscoe, M. K. (1998). Biochemica et Biophysics Acta 1396, 8-14.
Comell, K. A., Swarts, W. E., Barry, R. D. 8 Riscoe, M. K. (1996). Biochem.
B'rophys.
Res. Comm. 228, 724-732.
Degano, M., Gopaul, D. N., Scapin, G., Schramm, V. L. & Sacchettini, J. C.
(1996).
Biochemistry 35, 5971-5981.
Delta Ragione, F., Porcelli, M., Carteni-Farina, M., Zappia, V. & Pegg, A. E.
(1985).
Biochem. J. 232, 335-341.
Duerre, J. A. (1962). J. Biol. Chem. 237, 3737-3741.
Hendrickson, W. A. (1991). Science 254(5028), 51-58.
Jancarik, J. & Kim, S.-H. (1991). J. Appl. Cryst 24, 409-411.
Kamatani, N. & Carson, D. A. (1981). Biochim. Biophys. Acts 675, 344-350.
Kamatani, N., Kul~ta, M., Wllis, E. H., Frincke, L. A. & Carson, D. A. (1984).
Adv. Exp.
Med. Biol.(83-88).
Matthews, B. W. (1968). J. Mot. Biol. 33(2), 491-497.
Otwinowski, Z. & Minor, W., (1997). Methods in Enzymology. Edited by Carter Jr., C.
W., & Sweet, R.M.: Academic Press.
Pegg, A. E. 8~ Williams-Ashman, H. G. (1969). Biochem. J. 115, 241-247.
Riscoe, M. K., Ferro, A. J. & Fitchen, J. H. (1989). Parasitology Today S(10), 330-333.

Shimizu, S., Abe, T. & Yamada, H. (1988). FEMS Letters 51, 177-180.
Tumer, M., Yuan, C.-S., Borchardt, R. T., Hershfiekl, M. S., Smith, G. D. &
Howell, P. L.
(1998). Nat. Struct. Biol. 5, 369-376.
Walker, R. D. & Duerre, J. A. (1975). Can. J. Biochem. 53, 312-319.
Zappia, V., Delta Ragione, F. & Carteni-Farina, M., (1985). Biological Methylation and Drug Design: Expreimental and Clinical Roles of S-Adenosylmethionine. Edited by Borchardt, R., Creveling, C., & Ueland, P. Clifton, N.J.: The Humana Press Inc.
References re 3D Strucure Determination of E, coli MTAlAdoHcy Nucleosidase 1. Duerre, J.A. (1962). A hydrolytic nucelosidase acting on S-adenosylhomocysteine and on 5'-methyfthioadenosine. J. Biol. Chem. 237, 3737-3741.
2. Cornell, K.A. & Riscoe, M.K. (1998). Cloning and expression of Escherichia coli 5'-methylthioadenosinelS-adenosylhomocysteine nucleosidase: identification of the pfs gene product. Biochim. Biophys. Acta. 1396, 8-14.
3. Cornell, K.A., Swarts, W.E., Barry, R.D. & Riscoe, M.K. (1996).
Characterization of recombinant Escherichia coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase: analysis of enzymatic activity and substrate specificity.
Biochem.
Biophys. Res. Commun. 228, 724-32.
4. Sufin, J.R., Meshnick, S.R., Spiess, A.J., Garofalo-Hannan, J., Pan, X.Q. &
Bacchi, C.J. (1995). Methionine recycling pathways and antimalarial drug design.
Antimicrob. Agents Chemofher. 39, 2511-5.
5. Riscoe, M.K., Ferro, A.J. & Fitchen, J.H. (1989). Methionine recycling as a target for antiprotozoai drug development. Parasitology Today 5, 330-333.
6. de la Haba, G. & Cantoni, G. (1959). The enzymatic synthesis of S-adenosyl-L-homocysteine from adenosine and homocysteine. J. Biol. Chem. 234, 603-608.
7. Borchardt, R.T. (1980). S-Adenosyl-L-methionine-dependent macromolecule methyltransferases: potential targets for the design of chemotherapeutic agents. J.
Med. Chem. 23, 347-57.
8. Pajula, R.L. & Raina, A. (1979). Methylthioadenosine, a potent inhibitor of spermine synthase from bovine brain. FEES Lett. 99, 343-5.
9. Raina, A., Tuomi, K. & Pajula, R.L. (1982). Inhibition of the synthesis of polyamines and macromolecules by 5'-methylthioadenosine and 5'-alkylthiotubercidins in cells. Biochem. J. 204, 697-703.

10. Riscoe, M.K., Tower, P.A. 8~ Ferro, A.J. (1984). Mechanism of action of 5'-methylthioadenosine in S49 cells. Biochem. Pharmacol. 33, 3639-43.
11. Cerri, M.A., Beltran-Nunez, A., Bemasconi, S., Dejana, E., Bassi, L. &
Bazzoni, G.
(1993). Inhibition of cytokine production and endothelial expression of adhesion antigens by 5'-methylthioadenosine. Eur. J. Pharmacol. 232, 291-4.

12. Borchardt, R.T., Creveling, C.R. & Ueland, P.M. (1986). Biological methylation and drug design-Experimental and clinical roles of S-adenosylmethione. Humana Press: Clifton, NJ.

13. Comell, K.A., Winter, R.W., Tower, P.A. & Riscoe, M.K. (1996). AfFnity purification of 5-methylthioribose kinase and 5-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Klebsiella pneumoniae. Biochem. J. 317, 285-90.

14. Ferro, A.J., Barren, A. & Shapiro, S.K. (1976). Kinetic properties and the effect of substrate analogues on 5'-methylthioadenosine nucleosidase from Escherichia coli.
Biochim. Biophys. Acta. 438, 487-94.

15. Guranowski, A.B., Chiang, P.K. & Cantoni, G.L. (1981). 5'-Methylthioadenosine nucleosidase. Purification and characterization of the enzyme from Lupinus luteus seeds. Eur. J. Biochem. 114, 293-9.

16. Della Ragione, F., Porcelli, M., Carteni-Farina, M., Zappia, V. 8 Pegg, A.E. (1985).
Escherichia coli S-adenosylhomocysteine/5'-methylthioadenosine nucleosidase.
Purification, substrate specificity and mechanism of action. Biochem. J. 232, 41.

17. Ealick, S.E., al., e. & Bugg, C.E. (1990). Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution. J. Biol.
Chem.
265, 1812-20.
2;i 18. Lee, J.E., Comell, K.A., Riscoe, M.K. & Howell, P.L. (2001).
Expression, purification, crystallization and preliminary X-ray analysis of Escherichia coli 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase. Acta Cryst. D 57, 150-152.
19. Rao, S.T. & Rossmann, M.G. (1973). Comparison of super-secondary structures in 31) proteins. J. Mol. Biol. 76, 241-56.
20. Turner, M.A., Yang, X., Yin, D., Kuczera, K., Borchardt, R.T. 8 Howell, P.L. (2000).
Structure and function of S-adenosylhomocysteine hydrolase. Cell Biochemistry and Biophysics 33, 101-125.
21. Turner, M.A., Yuan, C.S., Borchardt, R.T., Hershfleld, M.S., Smith, G.D. &
Howell, 35 P.L. (1998). Structure determination of selenomethionyl S-adenosylhomocysteine hydrolase using data at a single wavelength. Nat. Struct. Biol. 5, 369-76.

22. Degano, M., Gopaul, D.N., Scapin, G., Schramm, V.L. 8 Saochettini, J.C.
(1996).
Three-dimensional structure of the inosine-urldine nucleoside N-ribohydrolase from Crithidia fasciculata. Biochemistry 35, 5971-81.
23. Ghoda, L.Y., et al. & Bacchi, C.J. (1988). Substrate specificities of 5'-deoxy-5'-methylthioadenosine phosphorylase from Trypanosoma brucei brucei and mammalian cells. MoL Biochem. Parasitol. 27, 109-18.
24. Toorchen, D. & Miller, R.L. (1991). Purification and characterization of 5'-deoxy-5'-methylthioadenosine (MTA) phosphorylase from human liver. Biochem. Pharmacol.
41, 2023-30.
25. Koellner, G., Luic, M., Shugar, D., Saenger, W. & Bzowska, A. (1997).
Crystal structure of calf spleen purine nucleoside phosphorylase in a complex with hypoxanthine at 2.15 A resolution. J. Mol. Biol. 265, 202-16.
26. Tebbe, J., et al. & Koellner, G. (1999). Crystal structure of the purine nucleoside phosphorylase (PNP) from Cellulomonas sp. and its implication for the mechanism of trimeric PNPs. J. Mol. Biol. 294, 1239-55.
27. Appleby, T.C., Erion, M.D. 8 Ealick, S.E. (1999). The structure of human 5'-deoxy-5' methylthioadenosine phosphorylase at 1.7 A resolution provides insights into substrate binding and catalysis. Structure 7, 629-41.
28. Jensen, K.F. (1978). Two purine nucleoside phosphorylases in Bacillus subtilis.
Purification and some properties of the adenosine-specific phosphorylase.
Biochim.
Biophys. Acta. 525, 346-356.
29. Mao, C., Cook, W.J., Zhou, M., Koszalka, G.W., Krenitsky, T.A. & Ealick, S.E. (1997).
The crystal structure of Escherichia coli purlne nucleoside phosphorylase: a comparison with the human enzyme reveals a conserved topology. Structure 5, 1373-83.
30. Koellner, G., Luic, M., Shugar, D., Saenger, W. 8~ Bzowska, A. (1998).
Crystal structure of the ternary complex of E. coli purine nucleoside phosphorylase with formycin B, a structural analogue of the substrate inosine, and phosphate (Sulphate) at 2.1 A resolution. J. Mol. Biol. 280, 153-66.
31. Allart, B., Gatel, M., Guillerm, D. & Guillerm, G. (1998). The catalytic mechanism of adenosylhomocysteinelmethylthioadenosine nucleasidase from Escherichia coli-chemical evidence for a transition state with a substantial oxocarbenium character.
Eur. J. Biochem. 256, 155-62.
32. Burley, S.K. & Petsko, G.A. (1985). Aromatio-aromatic interaction: a mechanism of protein structure stabilization. Science 228, 23-8.
33. Copley, R.R. & Barton, G.J. (1994). A structural analysis of phosphate and sulphate binding sites in proteins. Estimation of propensities for binding and conservation of phosphate binding sites. J. Mol. Biol. 242, 321-9.

34. Erion, M.D., Stoeckler, J.D., Guida, W.C., Walter, R.L. & Ealidc, S.E.
(1997). Purine nucleoside phosphorylase. 2. Catalytic mechanism. Biochemistry 36, 11735-48.
35. Fedorov, A., et al. & Almo, S.C. (2001). Transition State Structure of Purine Nucleoside Phosphorylase and Principles of Atomic Motion in Enzymatic Catalysis.
Biochemistry 40, 853-860.
36. Allart, B., Guillerm, D. & Guillerm, G. (1999). On the catalytic mechanism of adenosylhomocysteinelmethylthioadenosine nucleosidase from E. coll.
Nucleosides Nucleotides 18, 861-2.
37. Horenstein, B.A., Parkin, D.W., Estupinan, B. & Schramm, V.L. (1991).
Transition-state analysis of nucleoside hydrolase from Crithidia fasciculata.
Biochemistry 30, 10788-95.
38. Langsetmo, K., Fuchs, J.A. & Woodward, C. (1991). The conserved, buried aspartic acid in oxidized Escherichia coli thioredoxin has a pKa of 7.5. Its titration produces a related shift in global stability. Biochemistry 30, 7603-9.
39. Otwinowski, Z. & W, M. (1997). Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326.
40. Pflugrath, J.W. {1999). The finer things in X-ray diffraction data collection. Acta Cryst. D 55, 1718-25.
41. Brunger, A.T., et al. & Warren, G.L. {1998). Crystallography & NMR system:
A new software suite for macromolecular structure determination. Acta Cryst. D 54, 21.
42. Grosse-Kunstleve, R.W. & Brunger, A.T. (1999). A highly automated heavy-atom search procedure for macromolecular structures. Acta Cryst. D 55, 1568-77.
43. Ramakrishnan, V. & Biou, V. (1997). Treatment of multiwavelength anomalous diffraction data as a special case of multiple isomorphous replacement.
Methods Enzymol. 276, 538-57.
44. McRee, D.E. (1999). XtaIViewIXfit-A versatile program for manipulating atomic coordinates and electron density. J. Struct. Biol. 125, 156-65.
45. Brunger, A.T., Krukowski, A. & Erickson, J.W. (1990). Slow-cooling protocols for crystallographic refinement by simulated annealing. Acta Cryst. A 46, 585-93.
46. Laskowski, R.A., MacArthur, M.W., Moss, D.S. 8 Thomton, J.M. (1993).
PROCHECK:
a program to check the stereochemical quality of protein structures. J. Appl.
Cryst.
26, 283-291.
47. Morris, A.L., MacArthur, M.W., Hutchinson, E.G. & Thomton, J.M. (1992).
Stereochemical quality of protein structure coordinates. Proteins 12, 345-G4.
48. Evans, S.V. (1993). SETOR: hardware-lighted three-dimensional solid model representations of macromolecules. J. MoJ. Graph. 11, 134-8, 127-8.

49. Hutchinson, E.G. & Thomton, J.M. (1996). PROMOTIF-a program to identify and analyze structural motifs in proteins. Protein Sci. 5, 212-20.
50. Kraulis, P.J. (1991). MOLSCRIPT: A program to produce both detailed and schematic plots of protein structures. J. App!. Cryst. 1991, 946-950.
51. Merritt, E.A. & Bacon, D.L. (1997). Raster3D: photorealistic molecular graphics.
Methods Enzymol. 277, 505-524.
52. Gilbert, D., Westhead, D., Nagano, N. & Thomton, J. (1999). Motif based searching in TOPS protein topology databases. Bioinformatics 15, 317-26.
53. Westhead, D.R., Slidel, T.W., Flores, T.P. & Thomton, J.M. (1999). Protein structural topology: Automated analysis and diagrammatic representation. Protein Sci. 8, 904.
54. Westhead, D.R., Hatton, D.C. & Thomton, J.M. (1998). An atlas of protein topology cartoons available on the World-Wide Web. Trends Biochem. Sci. 23, 35-6.
55. Humphrey, W., Dalke, A. & Schulten, K. (1996). VMD-visual molecular dynamics. J. Mol. Graph. 14, 33-38.

Table 1.
ATOId 1 N MET A 1 -1.5.406-69.279-5.116 1.0035.16 N

ATOM 2 CA MET A 1 -14.674 -68.026-4.747 1.0035.95 C

ATOM 3 C MET A 1 -15.604 -66.836-4.529 1.0033.64 C

ATOM 4 0 MET A 1 -16.496 -66.577-5.336 1.0034.34 0 ATOM 5 CB MET A 1 -13.652 -67.671-5.830 1.0038.00 C

ATOM 6 CG MET A 1 -12.881 -66.396-5.540 1.0042.84 C

ATOM 7 SD MET A 1 '11.526 -66.085-6.679 1.0049.13 S

ATOM 8 CE MET A 1 -16.164 -66.065-5.567 1.0046.72 C

ATOM 9 N LYS A 2 -15.399 -66.128-3.421 1.0031.48 N

ATOM 10 CA LYS A 2 -16.194 -64.944-3.103 1.0029.16 C

ATOM 11 C LYS A 2 -15.243 -63.763-3.008 1.0027.78 C

ATOM 12 0 LYS A 2 -14.291 -63.790-2.241 1.0026.01 O

ATOM 13 CB LYS A 2 -16.926 -65.095-1.775 1.0028,01 C

ATOM 14 CG LYS A 2 -17.861 -63.909-1.506 1.0029.99 C

ATOM 15 CD LYS A 2 -18.582 -64.015-0.174 1.0029.28 C

ATOM 16 CE LYS A 2 -19.534 -65.192-0.135 1.0027.20 C

ATOM 17 NZ LYS A 2 -20.230 -65.2201.177 1.0028.96 N

ATOM 18 N ILE A 3 -15.514 -62.722-3.779 1.0027.88 N

ATOM 19 CA ILE A 3 -14.646 -61.559-3.795 1.0026.42 C

ATOM 20 C ILE A 3 -15.242 -60.374-3.060 1.0025.27 C

ATOM 21 0 ILE A 3 -16.339 -59.926-3.375 1.0025.43 0 A'fOM 22 CB ILE A 3 -14.319 -61.175-5.259 1.0027.63 C

A'fOM 23 CG1 ILE A 3 -13.602 -62.354-5.935 1.0029.70 C

ATOM 24 CG2 ILE A 3 -13.436 -59.922-5.305 1.0027.21 C

ATOM 25 CD1 ILE A 3 -13.281 -62.139-7.393 1.0031.90 C

ATOM 26 N GLY A 4 -14.522 -59.879-2.059 1.0023.91 N

P,TOM 27 CA GLY A 4 -15.000 -58.727-1.324 1.0023.50 C

F~TOM 28 C GLY A 4 -14.505 -57.497-2.064 1.0024.34 C

ATOM 29 0 GLY A 4 -13.364 -57.468-2.524 1.0025.29 0 ATOM 30 N ILE A 5 -15.368 -56.497-2.204 1.0023.83 N

ATOM 31 CA ILE A 5 -15.019 -55.264-2.893 1.0022.54 C

ATOM 32 C ILE A 5 -15.335 -54.099-1.964 1.0022.86 C

ATOM 33 0 ILE A 5 -16.465 -53.958-1.507 1.0023.00 0 ATOM 34 CB ILE A 5 -15.848 -55.091-4.192 1.0022.90 C

ATOM 35 CG1 ILE A 5 -15.655 -56.306-5.105 1.0022.95 C

ATOM 36 CG2 ILE A 5 -15.428 -53.822-4.927 1.0023.25 C

ATOM 37 CD1 ILEA 5 -16.644 -56.369-6.2591.00 21.59 C

ATOM 38 N ILEA 6 -14.327 -53.287-1.6581.00 22.94 N

ATOM 39 CA ILEA 6 -14.522 -52.116-0.8121.00 21.89 C

ATOM 40 C ILEA 6 -14.087 -50.939-1.6741.00 22.24 C

ATOM 41 0 ILEA 6 -12.916 -50.826-2.0411.00 22.71 0 ATOM 42 CB ILEA 6 -13.665 -52.1910.471 1.00 22.86 C

ATOM 43 CG1 ILEA 6 -14.044 -53.4471.263 1.00 22.79 C

ATOM 44 CG2 ILEA 6 -13.892 -50.9381.342 1.00 21.56 C

ATOM 95 CD1 ILEA 6 -13.288 -53.5972.563 1.00 21.46 C

ATOM 46 N GLYA 7 -15.044 -50.088-2.0291.00 23.35 N

ATOM 47 CA GLYA 7 -14.744 -48.945-2.8701.00 23.03 C

ATOM 48 C GLYA 7 -15.044 -47.620-2.2061.00 24.14 C

ATOM 49 O GLYA 7 -16.063 -47.468-1.5361.00 22.57 0 ATOM 50 N ALAA 8 -14.148 -46.657-2.3941.00 25.56 N

ATOM 51 CA ALAA 8 -14.317 -45.340-1.8001.00 26.71 C

ATOM 52 C ALAA 8 -15.057 -44.385-2.7371.00 28.09 C

ATOM 53 O ALAA 8 -15.556 -43.353-2.2921.00 29.52 0 ATOM 54 CB ALAA 8 -12.953 -44.756-1.4241.00 25.54 C

ATOM 55 N META 9 -15.128 -44.713-4.0271.00 26.45 N

ATOM 56 CA META 9 -15.834 -43.841-4.9691.00 28.12 C

ATOM 57 C META 9 -17.290 -44.274-5.0511.00 28.39 C

ATOM 58 O META 9 -17.613 -45.348-5.5631.00 26.17 0 ATOM 59 CB META 9 -15.180 -43.864-6.3641.00 26.44 C

ATOM 60 CG META 9 -13.783 -43.246-6.3831.00 25.44 C

ATOM 61 SD META 9 -13.003 -43.017-7,9931.00 22.73 S

ATOM 62 CE META 9 -12.337 -44.667-8.3101,00 23.72 C

ATOM 63 N GLUA 10 -18.164 -43.426-4.5241.00 28.44 N

ATOM 64 CA GLUA 10 -19.595 -43.693-4.4901.00 30.93 C

ATOM 65 C GLUA 10 -20.199 -44.107-5.8261.00 30.30 C

ATOM 66 O GLUA 10 -21.027 -45.020-5.8911.00 27.57 O

A'COM 67 CB GLUA 10 -20.329 -42.460-3.9741.00 32.25 C

ATOM 68 CG GLUA 10 -21.827 --42.595-4.0081.00 39.77 C

ATOM 69 CD GLUA 10 -22.446 -42.225-2.6851.00 44.15 C

ATOM 70 OE1 GLUA 10 -22.167 ~-42.928-1.6841.00 47.88 0 ATOM 71 OE2 GLUA 10 -23.199 -41.229-2.6431.00 44.24 0 ATOM 72 N GLUA 11 -19.790 -43.435-6.8941.00 30.09 N

ATOM 73 CA GLUA 11 -20.333 -43.744-8.2011.00 31.98 C

P,TOM 74 C GLUA 11 -19.920 -45.143-8.6401.00 30.31 C

AT014 75 0 GLU A 11 -20.679 -45.835-9.317 1.0030.15 O

ATOM 76 CB GLU A 11 -19.875 -42.704-9.221 1.0036.68 C

ATOM 77 CG GLU A 11 -20.625 -42.781-10.5391.0043.94 C

ATOM 78 CD GLU A 11 -20.141 -41.749-11.5361.0047.66 C

ATOM 79 OE1 GLU A 11 -20.107 -40.552-11.1741.0049.48 0 ATOM 80 OE2 GLU A 11 -19.795 -42.136-12.6771.0050.12 0 ATOM 81 N GLU A 12 -18.719 -45.563-8.259 1.0027.29 N

ATOM 82 CA GLU A 12 -18.270 -46.897-8.628 1.0026.68 C

ATOM 83 C GLU A 12 -19.108 -47.925-7.865 1.0025.95 C

ATOM 84 0 GLU A 12 -19.522 -48.932-8.430 1.0026.38 0 ATOM 85 CB GLU A 12 -16.782 -47.085-8.305 1.0024.32 C

ATOM 86 CG GLU A 12 -16.319 -48.544-8.403 1.0025.45 C

ATOM 87 CD GLU A 12 -14.915 -48.756-7.874 1.0028.16 C

ATOM 88 OE1 GLU A 12 -14.622 -49.870-7.381 1.0026.39 0 ATOM 89 OE2 GLU A 12 -14.100 -47.813-7.954 1.0027.62 0 ATOM 90 N VAL A 13 -19.360 -47.670-6.584 1.0026.92 N

ATOM 91 CA VAL A 13 -20.153 -48.595-5.779 1.0028.48 C

ATOM 92 C VAL A 13 -21.579 -48.709-6.327 1.0028.64 C

ATOM 93 0 VAL A 13 -22.163 -49.793-6.339 1.0029.22 0 ATOM 94 CB VAL A 13 -20.192 -48.154-4.292 1.0028.46 C

ATOM 95 CG1 VAL A 13 -2,1.134-49.055-3.498 1.0028.22 C

ATOM 96 CG2 VAL A 13 -18.776 -48.225-3.694 1.0027.83 C

ATOM 97 N THR A 14 -22.136 -47.594-6.790 1.0028.49 N

ATOM 98 CA THR A 14 -23.489 -47.605-7.338 1.0029.62 C

A'POM 99 C THR A 14 -23.525 -48.386-8.644 1.0030.20 C

ATOM 100 O THR A 14 -24.411 -49.221-8.860 1.0030.62 0 ATOM 101 CB THR A 14 -24.002 ~-46.173-7.597 1.0029.13 C

ATOM 102 OG1 THR A 14 -24.158 -45.497-6.345 1.0032.57 0 ATOM 103 CG2 THR A 14 -25.346 -46.202-8.327 1.0030.52 C

ATOM 104 N LEU A 15 -22.563 -48.110-9.518 1.0030.22 N

ATOM 105 CA LEU A 15 -22.486 -48.805-10.7981.0031.03 C

ATOM 106 C LEU A 15 -22.387 -50.311-10.5871.0030.67 C

ATOM 107 O LEU A 15 -23.084 -51.083-11.2491.0031.32 0 ATOM 108 CB LEU A 15 -21.274 -48.322-11.5961.0031.74 C

ATOM 109 CG LEU A 15 -21.374 -46.929-12.2241.0032.68 C

ATOM 110 CD1 LEU A 15 -20.013 -46.508-12.7671.0032.25 C

.ATOM 111 CD2 LEU A 15 -22.419 -46.952-13.3301.0031.33 C

ATOM 112 N LEU A 16 -21.522 -50.730-9.665 1.0029.49 N

ATOM 113 CA LEUA 16 -2.1.346-52.157-9.3841.00 28.44 C

ATOM 114 C LEUA 16 -22.569 -52.743-8.6851.00 29.42 C

ATOM 115 O LEUA 16 -23.002 -53.858-9.0041.00 28.30 0 ATOM 116 CB LEUA 16 -20.096 -52.388-8.5231.00 26.88 C

ATOM 117 CG LEUA 16 -18.730 -52.155-9.1761.00 26.30 C

ATOM 118 CD1 LEUA 16 -17.631 -52.355-8.1351.00 26.27 C

ATOM 119 CD2 LEUA 16 -18.526 -53.130-10.3331.00 26.82 C

ATOM 120 N ARGA 17 -23.124 -51.998-7.7321.00 29.75 N

ATOM 121 CA ARGA 17 -24.303 -52.459-6.9901.00 32.36 C

ATOM 122 C ARGA 17 -25.463 -52.773-7.9321.00 32.78 C

ATOM 123 0 ARGA 17 -26.130 -53.804-7.7951.00 31.76 0 ATOM 124 CB ARGA 17 -24.750 -51.389-5.9851.00 33.88 C

ATOM 125 CG ARGA 17 -25.979 -51.766-5.1681.00 36.15 C

ATOM 126 CD ARGA 17 -26.653 -50.522-4.6151.00 40.81 C

ATUM 127 NE ARGA 17 -27.040 -49.616-5.6991.00 46.64 N

ATUM 128 CZ ARGA 17 -27.620 -48.430-5.5241.00 49.95 C

ATOM 129 NH1 ARGA 17 -2'7.885-47.987-4.2991.00 50.80 N

ATIJM130 NH2 ARGA 17 -27.942 -47.685-6.5771.00 50.28 N

ATOM 131 N ASPA 18 -25.701 -51.875-8.8841.00 33.05 N

ATOM 132 CA ASPA 18 -26.787 -52.045-9.8441.00 35.03 C

ATOM 133 C ASPA 18 -26.594 -53.237-10.?691.00 34.57 C

ATOM 134 0 ASPA 18 -27.553 -53.712-11.3711.00 35.70 O

ATOM 135 CB ASPA 18 -26.961 -50.773-10.6831.00 37.08 C

A~'OM136 CG ASPA 18 -27.658 -49.660-9.9191.00 39.68 C

ATOM 137 OD1 ASPA 18 -27.678 -48.513-10.4181.00 40.78 O

ATOM 138 OD2 ASPA 18 -28.193 -49.935-8.8231.00 40.76 0 A~'OM139 N LYSA 19 -25.361 -53.719-10.8841.00 32.92 N

ATOM 140 CA LYSA 19 -25.073 -54.860-11.7461.00 32.87 C

A'POM141 C LYSA 19 -25.140 -56.197-11.0151.00 32.63 C

A'POM142 0 LYSA 19 -25.101 -57.255-11.6441.00 33.04 O

ATOM 193 CB LYSA 19 -23.694 -54.704-12.3961.00 33.34 C

ATOM 144 CG LYSA 19 -23.677 '53.738-13.5681.00 34.85 C

ATOM 145 CD LYSA 19 -22.281 -53.605-14.1601.00 38.07 C

ATOM 146 CE LYSA 19 -22.297 -52.769-15.4281.00 39.19 C

ATOM 147 NZ LYSA 19 -20,946 -52.684-16.0581.00 43.40 N

F~TOM148 N ILEA 20 -25.233 -56.154-9.6901.00 31.86 N

ATOM 149 CA ILEA 20 -25.298 -57.378-8.900I.00 31.80 C

ATOM 150 C ILE 20 -26.646 -58.0'76-9.0741.00 31.81 C
A

ATOM 151 0 ILEA 20 -27.698 -57.443-8.979 1.00 30.96 0 ATOM 152 CB ILEA 20 -25.080 -57.085-7.396 1.00 31.02 C

ATOM 153 CG1 ILEA 20 -23.640 -56.632-7.158 1.00 29.69 C

ATOM 154 CG2 ILEA 20 -25.382 -58.328-6.564 1.00 30.07 C

ATO!~1S5 CD1 ILEA 20 -2.3.361-56.231-5.732 1.00 27.99 C

ATOM 156 N GLUA 21 -26.600 -59.378-9.342 1.00 32.95 N

ATOM 157 CA GLUA 21 -27.810 -60.183'9.507 1.00 34.70 C

ATOM 158 C GLUA 21 -28.173 -60,807'8.167 1.00 33.68 C

ATOM 159 0 GLUA 21 -?.7.289-61.098-7.361 1.00 32.82 O

ATOM 160 CB GLUA 21 -27.581 -61.297-10.5311.00 38.48 C

ATOM 161 CG GLUA 21 -27.529 -60.824-11.9661.00 45.03 C

ATOM 162 CD GLUA 21 -28.795 -60.094-12.3631.00 49.25 C

ATOM 163 OE1 GLUA 21 -29.891 -60.679-12.2071.00 51.94 0 ATOM 164 OE2 GLUA 21 -28.697 -58.938-12.8281.00 51.86 0 ATOM 165 N ASNA 22 -29.469 -61.019-7.937 1.00 32.43 N

ATOM 166 CA ASNA 22 -29.946 -61.603-6.685 1.00 32.05 C

ATOM 167 C ASNA 22 -29,391 -60.795-5.522 1.00 32.66 C

ATOM 168 0 ASNA 22 -28.957 -61.349-4.516 1.00 31.49 0 ATOM 169 CB ASNA 22 -29.492 -63.063-6.567 1.00 30.86 C

ATOM 170 CG ASNA 22 -30.101 -63.951-7.641 1.00 31.20 C

ATOM 171 OD1 ASNA 22 -31.300 -63.887-7.899 1.00 29.96 O

ATOM 172 ND2 ASNA 22 -29.278 -64.787-8.268 1.00 29.84 N

ATOM 173 N ARGA 23 -29.428 -59.474-5.667 1.00 33.02 N

ATOM 174 CA ARGA 23 -28.897 -58.564-4.658 1.00 35.24 C

ATOM 175 C ARGA 23 -29.585 -58.599-3.300 1.00 35.00 C

ATOM 176 0 ARGA 23 -30.808 -58.511-3.202 1.00 34.63 0 ATOM 177 CB ARGA 23 -28.929 -57.123-5.172 1.00 35.79 C

ATOM 178 CG ARGA 23 -27.999 -56.192-4.404 1.00 40.45 C

A7.'OM179 CD ARGA 23 -28.558 -54.783-4.297 1.00 43.70 C

A7.'OM180 NE ARGA 23 -29.089 -54.297-5.565 1.00 47.90 N

ATOM 181 CZ ARGA 23 -29.601 -53.083-5.738 1.00 51.21 C

A'COM182 NH1 ARGA 23 -29.648 -52.231-4.720 1.00 52.55 N

ATOM 183 NH2 ARGA 23 -30.075 -52.721-6.924 1.00 53.06 N

ATOM 184 N GLNA 24 -28.773 -58.710-2.257 1.00 34.78 N

ATOM 185 CA GLNA 24 -29.240 -58.722-0.879 1.00 35.53 C

ATOM 186 C GLNA 24 -28.513 -57.567-0.208 1.00 35.57 C

ATOM 187 0 GLNA 24 -27.357 '57.289-0.527 1.00 33.71 0 ATOM 188 CB GLNA 24 -28.839 -60.023-0.178 1.00 37.55 C

ATOM 189 CG GLNA 24 -29.304 -61.288-0.8691.00 40.83 C

ATOM 190 CD GLNA 24 -30.808 -61..413-0.8791.00 44.01 C

ATOM 191 OE1 GLNA 24 -31.441 -61.5060.172 1.00 47.56 0 ATOM 192 NE2 GLNA 24 -31.394 -61.416-2.0681.00 46.67 N

ATOM 193 N THRA 25 -29.181 -56.8900.715 1.00 36.67 N

ATOM 194 CA THRA 25 -28.554 -55.7911.424 1.00 37.81 C

ATOM 195 C THRA 25 -28.484 -56.1322.903 1.00 40.04 C

ATOM 196 0 THRA 25 -29.497 -56.4493.526 1.00 40.84 O

ATOM 197 CB THRA 25 -29.325 -54.4761.236 1.00 37.45 C

ATOM 198 OG1 THRA 25 -29.291 -54.099-0.1441.00 37.37 0 ATOM 199 CG2 THRA 25 -28.689 -53.3692.056 1.00 38.93 C

ATOM 200 N ILEA 26 -27,273 -56.0773.449 1.00 40.59 N

ATC>M201 CA ILEA 26 -27.024 -56.3794.852 1.00 41.41 C

ATOM 202 C ILEA 26 -26.661 -55.0795.565 1.00 42.12 C

ATOM 203 0 ILEA 26 -25.733 -54.3815.151 1.00 42.08 0 ATOM 204 CB ILEA 26 -25.847 -57.3764.981 1.00 41.98 C

ATOM 205 CG1 ILEA 26 -26.154 -58.6424.174 1.00 43.54 C

ATOM 206 CG2 ILEA 26 -25.598 -57.7176.444 1.00 41.38 C

ATOM 207 CD1 ILEA 26 -24.997 -59.6234.100 1.00 44.35 C

ATOM 208 N SERA 27 -27.382 -54.7436.630 1.00 41.83 N

ATOM 209 CA SERA 27 -27.088 -53.5107.353 1.00 42.10 C

ATOM 210 C SERA 27 -26.548 -53.8038.748 1.00 41.31 C

ATOM 211 0 SERA 27 -27.266 -54.3179.605 1.00 41.35 0 ATOM 212 CB SERA 27 -28.340 -52.6387.440 1.00 44.07 C

ATOM 213 OG SERA 27 -27.989 -51.2967.741 1.00 48.79 0 ATOM 214 N LEUA 28 -25.277 -53.4688.968 1,00 39.27 N

ATOM 215 CA LEUA 28 -24.610 -53.71710.2471.00 39.09 C

ATOM 216 C LEUA 28 -23.700 -52.56610.6481.00 38.01 C

Ay'OM217 0 LEUA 28 -?.3.024-51.9879.804 1.00 36.63 O

ATOM 218 CB LEUA 28 -23.741 -54.96810.1591.00 41.12 C

ATOM 219 CG LEUA 28 -24.324 -56.2559.581 1.00 43.14 C

A'POM220 CD1 LEUA 28 -23.192 --57.2509.373 1.00 43.58 C

ATOM 221 CD2 LEUA 28 -25.389 -56.81210.5161.00 42.68 C

ATOM 222 N GLYA 29 -23.664 -52.26611.9441.00 37.69 N

ATOM 223 CA GLYA 29 -22.815 -51.19912.4481.00 37.20 C

ATOM 224 C GLYA 29 -22.861 -49.92211.6351.00 36.90 C

ATOM 225 0 GLYA 29 -21.849 -49.23411.4841.00 36.94 0 ATOM 226 N GLYA 30 -24.037 -49.60511.1071.00 36.21 N

ATOM 227 CA GLYA 30 -24.194 -48.39710.3151.00 37.45 C

ATOPA228 C GLYA 30 -23,642 -48.4988.903 1.00 37.16 C

ATOM 229 O GLYA 30 -23.464 -47.4848.232 1.00 36.95 O

ATOM 230 N CYSA 31 -23.367 -49.7198.451 1.00 36.72 N

ATOM 231 CA CYSA 31 -22.836 -49.9437.110 1.00 36.78 C

ATOM 232 C CYSA 31 -23.815 -50.7886.308 1.00 36.82 C

ATOM 233 0 CYSA 31 -24.635 -51.5106.878 1.00 36.71 0 ATOM 234 CB CYSA 31 -21.496 -50.6897.176 1.00 36.62 C

ATOM 235 SG CYSA 31 -20.214 -49.8908.165 1.00 39.99 S

ATOM 236 N GLUA 32 -23.732 -50.6934.986 1.00 34.86 N

ATOM 237 CA GLUA 32 -24.5$8 -51.4904.120 1.00 34.87 C

ATOM 238 C GLUA 32 -23.705 -52.3443.225 1.00 32.45 C

ATOM 239 0 GLUA 32 -22.844 -51.8202.517 1.00 31.01 0 ATOM 240 CB GLUA 32 -25.469 -50.6113.230 1.00 37.23 C

ATOM 241 CG GLUA 32 -26.564 -49.8523.948 1.00 43.42 C

ATOM 242 CD GLUA 32 -27.795 -49.6693.076 1.00 46.85 C

ATOM 243 OE1 GLUA 32 -27.645 -49.2771.897 1.00 47.08 0 ATOM 244 OE2 GLUA 32 -28.917 -49.9203.573 1.00 49.89 0 ATOM 245 N ILEA 33 -23.901 -5.3.6563.266 1.00 30.69 N

ATOM 246 CA ILEA 33 -23.122 -54.5472.417 1.00 28.80 C

ATOM 247 C ILEA 33 -24.065 -55.1831.398 1.00 29.31 C

ATOM 248 0 ILEA 33 -25.144 -55.6651.750 1.00 29.40 0 ATOM 249 CB ILEA 33 -22.428 -55.6553.232 1.00 28.32 C

ATOM 250 CG1 ILEA 33 -2:1.559 -55.0264.322 1.00 29.16 C

ATOM 251 CG2 ILEA 33 -21.572 -56.5252.305 1.00 24.95 C

ATOM 252 CD1 ILEA 33 -20.883 -56.0375.234 1.00 29.90 C

ATOM 253 N TYRA 34 -23.664 -55.1670.132 1.00 28.97 N

ATOM 254 CA TYRA 34 -24.482 -55.743-0.9271.00 29.41 C

ATOM 255 C TYRA 34 -23.856 -57.063-1.3351.00 30.65 C

ATOM 256 0 TYRA 34 -22.655 -57.126-1.6011.00 30.06 0 ATOM 257 CB TYRA 34 -24.525 -54.800-2.1301.00 30.42 C

ATOM 258 CG TYRA 34 -24.856 -53.376-1.7471.00 31.35 C

ATOM 259 CD1 TYRA 34 -26.138 -53.028-1.3331.00 31.83 C

ATOM 260 CD2 TYRA 34 -23.866 -52.396-1.7281.00 31.52 C

ATOM 261 CE1 TYRA 34 -26.425 -51.740-0.9001.00 32.95 C

ATOM 262 CE2 TYRA 34 -2.4.140 -51.104-1.2941.00 32.09 C

ATOM 263 CZ TYRA 34 -25.419 -50.785-0.8791.00 33.22 C

A'.COM264 OH TYRA 34 -25.689 -49.517-0.4201.00 33.59 0 ATOM 265 N THRA 35 -24.664 -58.117-1.377 1.00 28.58 N

ATOM 266 CA THRA 35 -24.161 -59.423-1.764 1.00 28.96 C

ATOM 267 C THRA 35 -24.987 -59.953-2.927 1.00 27.70 C

ATOM 268 O THRA 35 -26.124 -59.540-3.144 1.00 29.04 0 ATO'K269 CB THRA 35 -24.226 -60.438-0.596 1.00 29.14 C

ATOM 270 OG1 THRA 35 -25.593 -61).706-0.269 1.00 28.88 0 ATOM 271 CG2 THRA 35 -23.524 -5'9.8820.628 1.00 28.85 C

ATOM 272 N GLYA 36 -24.398 -60.869-3.675 1.00 27.76 N

ATOM 273 CA GLYA 36 -25.076 -61.436-4.817 1.00 28.90 C

ATOM 274 C GLYA 36 -24.001 -61.818-5.801 1.00 29.40 C

ATOM 275 0 GLYA 36 -22.849 -62.013-5.414 1.00 29.93 0 ATOM 276 N GLNA 37 -24.356 -61.918-7.073 1.00 29.09 N

ATOM 277 CA GLNA 37 -23.369 -62.285-8.065 1.00 28.98 C

ATOM 278 C GLNA 37 -23.123 -61.183-9.081 1.00 28.67 C

ATOM 279 O GLNA 37 -24.059 -60.514-9.522 1.00 27.60 0 ATC>M280 CB GLNA 37 -23.802 -63.562-8.803 1.00 28.35 C

ATC)M281 CG GLNA 37 -24.070 -64.764-7.896 1.00 29.99 C

ATOM 282 CD GLNA 37 -25.961 -64.739-7.297 1.00 27.24 C

ATOM 283 OE1 GLNA 37 -26.454 -64.708-8.022 1.00 30.59 0 ATOM 284 NE2 GLNA 37 -25.543 -64.751-5.970 1.00 26.77 N

ATOM 285 N LEUA 38 -21.851 -60.998-9.428 1.00 27.87 N

ATOM 286 CA LEUA 38 -21.448 -60.031-10.4411.00 29.43 C

ATc)M287 C LEUA 38 -20.982 -60.899-11.6051.00 29.71 C

ATOM 288 0 LEUA 38 -19.921 -61.524-11.5391.00 30.54 0 ATOM 289 CB LEUA 38 -20.292 -59.153-9.943 1.00 28.34 C

ATOM 290 CG LEUA 38 -19.757 -58.091-10.9121.00 28.77 C

ATOM 291 CD1 LEUA 38 -20.899 -57.218-11.3991.00 29.49 C

ATOM 292 CD2 LEUA 38 -18.684 -57.242-10.2201.00 28.25 C

ATOM 293 N ASNA 39 -21.785 -60.958-12.6611.00 30.55 N

ATOM 294 CA ASNA 39 -21.447 -61.779-13.8171.00 31.11 C

ATOM 295 C ASNA 39 -21.195 -63.221-13.4051.00 30.89 C

ATOM 296 0 ASNA 39 -20.267 -63.862-13.9001.00 29.95 0 ATOM 297 CB ASNA 39 -20.214 -61.224-14.5361.00 33.15 C

ATOM 298 CG ASNA 39 -20.455 -59.846-15.1071.00 33.82 C

ATOM 299 OD1 ASNA 39 -21.439 -59.628-15.8071.00 35.35 0 A'.COM300 ND2 ASNA 39 -19.565 -58.906-14.8061.00 33.62 N

A'~OM301 N GLYA 40 -22.014 -63.719-12.4801.00 30.92 N

A'COM302 CA GLYA 40 -21.883 -65.098-12.0331.00 30.44 C

ATOM 303 C GLY A 40 -20.970 -65.377-10.8541.00 30.42 C

ATOM 304 0 GLY A 40 -20.998 -66.477-10.2891.00 29.59 0 ATOf9305 N THR A 41 -20.154 -64.401-10.4741.00 30.20 N

ATOM 306 CA THR A 41 -19.233 -64.584-9.354 1.00 28.99 C

ATOM 307 C THR A 41 -1.9.792 -63.966-8.074 1.00 28.01 C

ATOM 308 0 THR A 41 -20.284 -6:?.840-8.086 1.00 28.00 0 ATOM 309 CB THR A 41 -17.859 -63.941-9.655 1.00 30.62 C

ATOM 310 OG1THR A 41 -1.7.345 -64.458-10.8901.00 29.08 0 ATOM 311 CG2THR A 41 -16.873 -64.244-8.537 1.00 27.92 C

ATOM 312 N GLU A 42 -19.720 -69.705-6.970 1.00 26.30 N

ATOM 313 CA GLU A 42 -20.227 -64.202-5.693 1.00 26.79 C

ATOM 314 C GLU A 42 -19.376 -63.023-5.232 1.00 25.67 C

ATOM 315 0 GLU A 42 -18.151 -63.104-5.241 1.00 25.78 0 ATOM 316 CB GLU A 42 -20.170 -65.300-4.623 1.00 27.86 C

ATOM 317 CG GLU A 42 -21.010 -66.527-4.937 1.00 28.87 C

ATOM 318 CD GLU A 42 -22.483 -66.286-4.724 1.00 31.53 C

ATOM 319 OE1GLU A 42 -22.900 -65.111-4.643 1.00 29.83 0 ATOM 320 OE2GLU A 42 -23.235 -67.280-4.640 1.00 33.67 0 ATOM 321 N VAL A 43 -20.029 -61.933-4.842 1.00 24.90 N

ATOM 322 CA VAL A 43 -19.319 -60.762-4.355 1.00 25.70 C

ATOM 323 C VAL A 43 -20.005 -60.183-3.126 1.00 26.22 C

ATOM 324 0 VAL A 43 -21.159 -60.505-2.821 1.00 26.56 0 ATOM 325 CB VAL A 43 -19.226 -59.640-5.434 1.00 26.22 C

ATOM 326 CG1VAL A 43 -18.416 -60.127-6.619 1.00 23.96 C

ATOM 327 CG2VAL A 43 -20.624 -59.203-5.878 1.00 25.79 C

ATOM 328 N ALA A 44 -19.266 -59.346-2.409 1.00 24.15 N

ATOM 329 CA ALA A 44 -19.763 -58.659-1.229 1.00 24.95 C

ATOM 330 C ALA A 44 -19.169 -57.274-1.434 1.00 24.32 C

ATOM 331 O ALA A 44 -17.951 -57.108-1.439 1.00 25.86 0 ATOM 332 CB ALA A 44 -19.226 -59.3070.039 1.00 23.90 C

ATOM 333 N LEU A 45 -20.045 -56.295-1.628 1.00 24.51 N

ATOM 334 CA LEU A 45 -19.655 -54.916-1.910 1.00 23.73 C

ATOM 335 C LEU A 45 -19.975 -53.939-0.788 1.00 23.40 C

ATOM 336 0 LEU A 45 -21.066 -53.958-0.224 1.00 24.08 0 ATOM 337 CB LEU A 95 -20.353 -54.480-3.198 1.00 22.51 C

ATOM 338 CG LEU A 95 -2Ø287 -53.041-3.701 1.00 22.52 C

ATOM 339 CD1LEU A 45 -18.875 -52.687-4.129 1.00 22.73 C

ATOM 340 CD2LEU A 45 -21.236 -52.915-4.880 1.00 22.60 C

ATOM 341 N LEUA 46 -19.021 -53.066-0.4831.00 24.13 N

ATO1H342 CA LEUA 46 -19.198 -52.0910.579 1.00 24.07 C

ATOM 343 C LEUA 46 -18.549 -50.7660.238 1.00 25.40 C

ATOM 344 0 LEUA 46 -17,462 -50.733-0.3401.00 25.08 0 ATOM 345 CB LEUA 46 -18.581 -52.6211.874 1.00 24.66 C

ATOM 346 CG LEUA 46 -18.307 -51.6142.996 1.00 25.71 C

ATOM 347 CD1 LEUA 46 -19.605 -51.2443.709 1.00 27.42 C

ATOM 348 CD2 LEUA 46 -17.324 -52.2283,977 1.00 29.10 C

ATOM 349 N LYSA 47 -19.229 -49.6760.589 1.00 25.14 N

ATOM 350 CA LYSA 47 -18.699 -48.3360.376 1.00 26.52 C

ATOM 351 C LYSA 47 -17.772 -48.0821.568 1.00 26.01 C

ATOM 352 0 LYSA 47 -18.163 -48.2532.725 1.00 26.09 0 ATCM 353 CB LYSA 47 -19.841 -47.3130.351 1.00 29.26 C

ATOM 354 CG LYSA 47 -19.420 -45.8500.490 1.00 34.97 C

ATOM 355 CD LYSA 47 -18.650 -45.348-0.7121.00 37.03 C

ATOM 356 CE LYSA 47 -18.387 -43.848-0.6051.00 39.25 C

ATOM 357 NZ LYSA 47 -17.515 -43.4860.560 1.00 42.96 N

ATOM 358 N SERA 48 -16.541 -47.6801.280 1.00 25.55 N

ATOM 359 CA SERA 48 -15.543 -97.4292.316 1.00 25.95 C

ATOM 360 C SERA 48 -15.850 -46.2693.268 1.00 25.01 C

ATOM 361 0 SERA 48 -16.360 -45.2272.851 1.00 24.29 0 ATOM 362 CB SERA 98 -14.183 -47.1741.658 1.00 24.78 C

ATOM 363 OG SERA 48 -13.182 -47.1002.649 1.00 30.28 0 ATOM 364 N GLYA 49 -15.541 -46.4624.549 1.00 24.57 N

ATC>M365 CA GLYA 49 -15.729 -45.9005.526 1.00 23.46 C

ATOM 366 C GLYA 49 -14.559 -44.4315.365 1.00 23.38 C

ATOM 367 0 GLYA 49 -13.598 -44.7394.653 1.00 20.14 0 ATOM 368 N ILEA 50 -14.631 -43.2686.012 1.00 23.52 N

ATOM 369 CA ILEA 50 -13.576 -42.2495.918 1.00 23.04 C

ATOM 370 C ILEA 50 -12.662 -42.3007.138 1.00 22.17 C

ATOM 371 0 ILEA 50 -13.125 -42.2368.280 1.00 22.71 0 ATOM 372 CB ILEA 50 -14.185 -40.8195.834 1.00 25.57 C

ATOM 373 CG1 ILEA 50 -15.213 -40.7514.703 1.00 26.14 C

ATOM 374 CG2 ILEA 50 -13.073 -39.7745.638 1.00 22.89 C

ATOM 375 CD1 ILEA 50 -1.4.660 -41.0693.332 1.00 31.36 C

ATOM 376 N GLYA 51 -11.360 -42.4146.898 1.00 21.58 N

ATOM 377 CA GLYA 51 -10.423 -42.9697.995 1.00 19.66 C

A7.'OM378 C GLYA 51 -10.137 -43.9098.377 1.00 22.34 C

ATOM 379 0 GLY A 51 -10.901 -44.8078.035 1.00 21.18 0 AT014380 N LYS A 52 -9.053 -44.1079.114 1.00 23.03 N

ATOM 381 CA LYS A 52 -8.626 -45.4449.526 1.00 23.54 C

ATOM 382 C LYS A 52 -9.636 -46.27610.3141.00 22.54 C

ATOM 383 0 LYS A 52 -9.881 -4'7.4359.977 1.00 21.85 0 ATOM 384 CB LYS A 52 -7.312 -45.33210.3111.00 24.89 C

ATOM 385 CG LYS A 52 -6.149 -44.9099.922 1.00 28.49 C

ATOM 386 CD LYS A 52 -5.009 -44.20610.1771.00 28.34 C

ATOM 387 CE LYS A 52 -4.304 -45.12811.1311.00 26.54 C

ATOM 388 NZ LYS A 52 -3.032 -44.51111.5871.00 24.84 N

ATOM 389 N VAL A 53 -10.230 -45.70411.3541.00 20.99 N

ATOM 390 CA VAL A 53 -11.186 -46.47212.1561.00 22.17 C

ATOM 391 C VAL A 53 -12.497 -46.80211.4471.00 22.54 C

ATOM 392 O VAL A 53 -12.991 -47.92211.5651.00 19.92 O

ATOM 393 CB VAL A 53 -11.4?9 -95.76113.5171.00 22.34 C

ATOM 394 CG1VAL A 53 -12.698 -46.37414.2121.00 20.96 C

ATOM 395 CG2VAL A 53 -10.262 -45.90614.4201.00 21.73 C

ATOM 396 N ALA A 59 -13.064 -45.84810.7081.00 22.12 N

ATOM 397 CA ALA A 54 -14.323 -46.10910.0111.00 23.39 C

ATOM 398 C ALA A 54 -14.113 -97.1188.893 1.00 24.10 C

ATOM 399 O ALA A 54 -14.990 -47.9358.614 1.00 23.69 0 ATOM 400 CB ALA A 54 -14.907 -44.8169.453 1.00 23.24 C

ATOM 401 N ALA A 55 -12.949 -47.0618.254 1.00 23.19 N

ATOM 402 CA ALA A 55 -12.632 -47.9937.185 1.00 23.79 C

ATOM 403 C ALA A 55 -12.409 -49.3847.791 1.00 24.68 C

ATOM 404 0 ALA A 55 -12.826 -50.3977.221 1.00 26.01 0 ATOM 405 CB ALA A 55 -11.378 -47.5256.431 1.00 22.52 C

ATOM 406 N ALA A 56 -11.750 -49.4268.946 1.00 22.05 N

ATOM 407 CA ALA A 56 -11.480 -50.6809.637 1.00 23.55 C

ATOM 408 C ALA A 56 -12.791 -51.31410.1131.00 23.64 C

ATOM 409 0 ALA A 56 -12.961 -52.53510.0561.00 22.88 0 ATOM 410 CB ALA A 56 -10.554 -50.42810.8301.00 21.05 C

ATOM 411 N LEU A 57 -13.716 -50.47510.5741.00 23.01 N

ATOM 412 CA LEU A 57 -15.010 -50.94711.0561.00 24.81 C

ATOM 413 C LEU A 57 -15.752 -51.6879.942 1.00 25.45 C

ATOM 414 O LEU A 57 -16.170 -52.83610.1171.00 25.86 O

ATOM 415 CB LEU A 57 -15.851 -49.75811.5601.00 23.75 C

ATOM 416 CG LEU A 57 -1.7.133 -50.07412.3461.00 26.45 C

ATOM 417 CD1LEU A 57 -17.534 -98.86213.189 1.0025.34 C

ATOM 418 CD2LEU A 57 -18.257 -50.46311.398 1.0025.33 C

ATOM 419 N GLY A 58 -15.911 -51.0248.800 1.0024.64 N

ATOM 420 CA GLY A 58 -16.600 -5:1.6327.677 1.0025.01 C

ATOM 421 C GLY A 58 -15.922 -52.8917.168 1.0025.03 C

ATOM 422 0 GLY A 58 -16.590 -53.8976.917 1.0024.87 O

ATOM 423 N ALA A 59 -14.601 -52.8397.016 1.0024.86 N

ATOM 424 CA ALA A 59 -13.840 -53.9896.533 1.0025.20 C

ATOM 425 C ALA A 59 -13.978 -55.1867.466 1.0024.46 C

ATOM 426 0 ALA A 59 -14.079 -56.3207.005 1.0025.51 0 ATOM 427 CB ALA A 59 -12.372 -53.6186.374 1.0022.62 C

ATOM 928 N THR A 60 -13.973 -54.9328.774 1.0025.37 N

ATOM 429 CA THR A 60 -14.100 -55.9969.768 1.0025.59 C

ATOM 430 C THR A 60 -15.475 -56.6609.649 1.0025.44 C

ATCM 431 0 THR A 60 -15.592 -57.8889.682 1.0025.59 0 ATOM 432 CB THR A 60 -13.927 -55.44911.218 1.0026.52 C

ATOM 433 OG1THR A 60 -12.618 -54.88411.374 1.0026.58 O

ATOM 434 CG2THR A 60 -14.093 -56.56112.232 1.0023.50 C

ATOM 435 N LEU A 61 -16.514 -55.8469.508 1.0025.38 N

ATOM 436 CA LEU A 61 -17.866 -56.3739.382 1.0025.62 C

ATOM 437 C LEU A 61 -17.983 -57.2328.138 1.0026.59 C

ATC>M438 0 LEU A 61 -18.540 -58.3308.185 1.0026.36 O

ATOM 439 CB LEU A 61 -18.886 -55.2329.322 1.0025.58 C

ATC)M440 CG LEU A 61 -19.159 -54.54410.662 1.0027.26 C

ATOM 441 CD1LEU A 61 -20.081 -53.35710.474 1.0027.36 C

ATOM 442 CD2LEU A 61 -19.771 -55.55811.620 1.0027.90 C

ATUM 443 N LEU A 62 -17.443 -56.7397.026 1.0027.35 N

ATOM 444 CA LEU A 62 -17.507 -57.4675.761 1.0028.01 C

ATOM 445 C LEU A 62 -16.736 -58.7785.810 1.0028.27 C

ATOM 446 0 LEU A 62 -1'7.261 -59.8195.415 1.0028.49 0 AT(JM447 CB LEU A 62 -16.980 -56.5964.610 1.0028.34 C

ATOM 448 CG LEU A 62 -17.104 '57.1563.180 1.0030.10 C

ATOM 449 CD1LEU A 62 -16.976 -56.0282.172 1.0034.11 C

ATOM 450 CD2LEU A 62 -16.035 -58.1872.919 1.0030.50 C

ATOM 451 N LEU A 63 -15.495 -58.7296.287 1.0027.28 N

ATOM 452 CA LEU A 63 -14.671 -59.9296.368 1.0028.98 C

ATOM 453 C LEU A 63 -15.261 -60.9987.290 1.0029.98 C

ATOM 454 O LEU A 63 -15.212 -62.1896.983 1.0031.74 O

ATOM 455 CB LEU A 63 -13.253 -59.5686.829 1.0028.64 C

ATOM 456 CG LEU A 63 -12.371 -58.8835.774 1.0029.16 C

ATOM 457 CD1LEU A 63 -11.086 -58.3766.399 1.0029.86 C

ATOM 458 CD2LEU A 63 -12.062 -59.8764.663 1.0033.36 C

ATOM 459 N GLU A 64 -15.828 -60.5728.410 1.0030.18 N

ATOM 460 CA GLU A 64 -16.399 -61.5069.368 1.0032.61 C

ATOM 461 C GLU A 64 -17.748 -62.0728.950 1.0032.65 C

ATOM 462 0 GLU A 64 -18.001 -63.2669.097 1.0032.86 0 ATOM 463 CB GLU A 64 -16.537 -60.83910.740 1.0033.56 C

ATOM 464 CG GLU A 64 -17.199 -61.73211.774 1.0037.61 C

ATOM 465 CD GLU A 64 -16.471 -63.05611.954 1.0040.75 C

ATOM 466 OE1GLU A 64 -17.105 -64.00912.457 1.0043.95 O

ATOM 967 OE2GLU A 64 -15.270 -63.14811.601 1.0040.45 0 ATOM 468 N HIS A 65 -18.616 -61.2138.437 1.0032.14 N

ATOM 469 CA HIS A 65 -19.945 -61.6388.029 1,0034.34 C

ATOM 470 C HIS A 65 -20.008 -62.3586.676 1.0034.96 C

ATGM 471 0 HIS A 65 -20.764 -63.3226.520 1.0034.24 O

ATOM 472 CB HIS A 65 -20.876 -60.4238.016 1.0036.38 C

ATOM 473 CG HIS A 65 -22.320 -60.7697.839 1.0041.22 C

ATOM 474 ND1HIS A 65 -22.839 -61.2166.642 1.0043.20 N

ATGM 475 CD2HIS A 65 -23.355 -60.7468.713 1,0042.61 C

ATOM 476 CE1HIS A 65 -24.131 -61.4536.787 1.0042.42 C

ATOM 477 NE2HIS A 65 -24.469 -61.1758.034 1.0042.90 N

ATOM 478 N CYS A 66 -19.209 -61.9145.?06 1.0032.08 N

ATC>M479 CA CYS A 66 -19.234 -62.5164.371 1.0031.39 C

ATOM 480 C CYS A 66 -18.088 -63.4694.086 1.0031.52 C

ATOM 481 0 CYS A 66 -18.137 -64.2333.121 1.0030.99 0 ATOM 482 CB CYS A 66 -19.235 -61.4213.310 1.0030.67 C

ATOM 483 SG CYS A 66 -20.582 -60.2713.500 1.0037.46 S

ATOM 484 N LYS A 67 -17.054 -63.4054.915 1.0032.26 N

ATOM 485 CA LYS A 67 -15.885 -64.2589.770 1.0033.59 C

ATOM 486 C LYS A 67 -15.453 -64.4643.317 1.0033.79 C

ATIJM487 O LYS A 67 -15.485 -65.5812.793 1.0033.15 O

ATCJM488 CB LYS A 67 -16.146 -65.6035.458 1.0036.55 C

ATOM 489 CG LYS A 67 -16.469 -65.4396.945 1.0039.19 C

ATOM 490 CD LYS A 67 -16.620 -66.7697.660 1.0041.78 C

ATOM 491 CE LYS A 67 -16.975 -66.5559.130 1.0042.49 C

ATOM 492 NZ LYS A 67 -18.317 -65.9169.295 1.0042.74 N

ATOM 493 N PRO A 68 -15.036 -63.3772.645 1.0032.87 N

ATOM 494 CA PRO A 68 -14.596 -63.4631.252 1.0031.85 C

ATOM 495 C PRO A 68 -13.208 -64.0861.161 1.0031.33 C

ATOM 496 0 PRO A 68 -12.483 -64.1442.154 1.0032.59 0 ATOM 497 CB PRO A 68 -14.607 -62.0070.803 1.0032.78 C

ATOM 498 CG PRO A 68 -14.186 -61.2902.055 1.0033.31 C

ATOM 499 CD PRO A 68 -15.021 -61.9783.115 1.0033.24 C

ATOM 500 N ASP A 69 -:L2.839-64.543-0.030 1.0029.96 N

ATOM 501 CA ASP A 69 -11.533 -65.158-0.245 1.0028.37 C

ATOM 502 C ASP A 69 -1Ø476-64.099-0.505 1.0028.30 C

ATOM 503 O ASP A 69 -9.297 -64.297-0.218 1.0027.44 0 ATOM 504 CB ASP A 69 -11.595 -66.104-1.440 1.0029.05 C

ATOM 505 CG ASP A 69 -12.569 -67.234-1.225 1.0032.19 C

ATOM 506 OD1 ASP A 69 -:12.255-68.132-0.418 1.0032.53 0 ATOM 507 OD2 ASP A 69 -13.653 -67.212-1.847 1.0033.97 0 ATOM 508 N VAL A 70 -10.897 -62.972-1.063 1.0026.92 N

ATOM 509 CA VAL A 70 -9.956 -61.899-1.359 1.0026.92 C

ATOM 510 C VAL A 70 -10.646 -60.555-1.224 1.0026.65 C

ATOM 511 O VAL A 70 -11.875 -60.470-1.293 1.0025.75 0 ATOM 512 CB VAL A 70 -9.418 -61.987-2.811 1.0028.20 C

ATCM 513 CG1 VAL A 70 -$.730 -63.328-3.049 1.0029.40 C

ATOM 514 CG2 VAL A 70 -10.559 -61.799-3.794 1.0028.32 C

ATOM 515 N ILE A 71 -9.841 -59.507-1.093 1.0024.77 N

ATOM 516 CA ILE A 71 -10.359 -58.156-0.999 1.0025.11 C

ATOM 517 C ILE A 71 -9.715 -57.295-2.082 1.0025.82 C

ATOM 518 0 ILE A 71 -$.494 -57.337-2.283 1.0026.19 0 ATOM 519 CB ILE A 71 -10.060 -57.5100.389 1.0024.66 C

ATOM 520 CG1 ILE A 71 -10.985 -58.0981.469 1.0024.88 C

ATOM 521 CG2 ILE A 71 -10.252 -56.0090.312 1.0022.95 C

ATOM 522 CDl ILE A 71 -12.467 -57.7681.268 1.0023.97 C

ATUM 523 N ILE A 72 -10.556 -56.555-2.799 1.0024.65 N

ATOM 524 CA ILE A 72 -10.119 -55.620-3.820 1.0023.57 C

ATOM 525 C ILE A 72 -10.622 -54.314-3.231 1.0024.59 C

ATOM 526 0 ILE A 72 -11.830 -54.154-3.024 1.0025.45 0 ATOM 527 CB ILE A 72 -10.825 -55.833-5.164 1.0024.34 C

ATOM 528 CG1 ILE A 72 -10.457 -57.193-5.752 1.0022.48 C

ATOM 529 CG2 ILE A 72 -10.414 -54.726-6.140 1.0024.52 C

ATOM 530 CD1 ILE A 72 -11.314 -57.557-6.951 1.0026.75 C

ATOM 531 N ASN A 73 -9.698 -53.400-2.948 1.00 23.21 N

ATOM 532 CA ASN A 73 -10.017 -52.115-2.344 1.00 21.68 C

ATOM 533 C ASN A 73 -9.676 -51.018-3.339 1.00 22.58 C

AT01M534 0 ASN A 73 -8.509 -5().810-3.663 1.00 22.44 0 ATOM 535 CB ASN A 73 -9.191 -5:1.960-1.068 1.00 22.40 C

ATOM 536 CG ASN A 73 -9.320 -50.587-0.436 1.00 21.39 C

ATOM 537 ODlASN A 73 -8.346 -50.0550.094 1.00 24.26 O

ATOM 538 ND2ASN A 73 -10.517 -50.014-0.474 1.00 19.53 N

ATOM 539 N THR A 74 -10.700 -50.313-3.813 1.00 23.44 N

ATOM 540 CA THR A 74 -10.520 -49.254-4.802 1.00 23.60 C

ATOM 541 C THR A 74 -10.830 -47.866-4.243 1.00 22.25 C

ATOM 542 0 THR A 74 -11.478 -47.735-3.212 1.00 21.63 0 ATOM 543 CB THR A 74 -11.452 -49.474-6.010 1.00 25.63 C

ATOM 544 OG1THR A 74 -12.815 -49.462-5.559 1.00 26.27 0 ATOM 545 CG2THR A 79 -11.170 -50.805-6.678 1.00 24.67 C

ATOM 546 N GLY A 75 -10.374 -46.835-4.945 1.00 22.25 N

ATOM 547 CA GLY A 75 -10.632 -45.466-4.523 1.00 22.83 C

ATOM 548 C GLY A 75 -<1.768 -44.511-5.324 1.00 22.64 C

ATOM 549 0 GLY A 75 -9.363 -94.832-6.439 1.00 22.63 0 ATOM 550 N SER A 76 -9.493 -93.338-4.763 1.00 24.37 N

ATOM 551 CA SER A 76 -8.641 -42.344-5.412 1.00 23.56 C

ATUM 552 C SER A 76 -'7.543 -41.970-4.421 1.00 23.79 C

ATUM 553 0 SER A 76 -'7.656 -42.236-3.221 1.00 22.65 0 ATOM 554 CB SER A 76 -9.446 -41.096-5.812 1.00 23.44 C

ATOM 555 OG SER A 76 -10.010 -40.454-4.676 1.00 24.71 0 ATOM 556 N ALA A 77 -6.472 -41.358-4.915 1.00 24.30 N

ATOM 557 CA ALA A 77 -5.378 -40.982-4.036 1.00 25.50 C

ATOM 558 C ALA A 77 -4.547 -39.848-4.613 1.00 25.52 C

ATOM 559 0 ALA A 77 -4.589 -39.583-5.813 1.00 26.55 0 ATOM 560 CB ALA A 77 -4.483 -42.190-3.779 1.00 23.11 C

ATOM 561 N GLY A 78 -3.803 -.39.174-3.741 1.00 24.76 N

ATOM 562 CA GLY A 78 -2.931 -38.109-4.194 1.00 24.27 C

ATOM 563 C GLY A 78 -1.605 -38.751-4.562 1.00 25.68 C

ATOM 564 0 GLY A 78 -1.135 -39.667-3.871 1.00 25.03 0 ATOM 565 N GLY A 79 -1.002 -38.296-5.655 1.00 25.67 N

ATOM 566 CA GLY A 79 0.267 -38.859-6.077 1.00 26.86 C

ATOM 567 C GLY A 79 1.446 -38.185-5.396 1.00 28.54 C

ATOM 568 0 GLY A 79 1.428 '36.972-5.159 1.00 27.72 0 AT01K569 N LEU A 80 2.463 -3E3.977-5.064 1.00 28.42 N

ATOM 570 CA LEU A 80 3.668 -38.464-4.419 1.00 29.30 C

ATOM 571 C LEU A 80 4.839 -38.586-5.388 1.00 31.51 C

ATOM 572 0 LEU A 80 5.696 -3'7.705-5.444 1.00 32.34 0 ATOM 573 CB LEU A 80 3.975 -39.250-3.145 1.00 28.42 C

ATOM 574 CG LEU A 80 2.958 -39.206-2.008 1.00 27.55 C

ATOM 575 CD1LEU A 80 3.389 -40.184-0.917 1.00 25.65 C

ATOM 576 CD2LEU A 80 2.850 -37.784-1.460 1.00 25.77 C

ATOM 577 N ALA A 81 4.872 -39.680-6.150 1.00 31.27 N

ATOM 578 CA ALA A 81 5.932 -39.890-7.136 1.00 32.31 C

ATOM 579 C ALA A 81 5.744 -38.828-8.219 1.00 32.68 C

ATOM 580 0 ALA A 81 4.677 -38.734-8.818 1.00 31.68 0 ATCM 581 CB ALA A 81 5.823 -41.288-7.744 1.00 31.95 C

ATOM 582 N PRO A 82 6.785 -38.017-8.482 1.00 33.76 N

ATOM 583 CA PRO A 82 6.778 -36.938-9.479 1.00 34.50 C

ATGM 584 C PRO A 82 6.428 -37.367-10.9001.00 35.42 C

ATOM 585 0 PRO A 82 5.904 -36.580-11.6801.00 36.87 0 ATOM 586 CB PRO A 82 8.206 -36.386-9.409 1.00 35.71 C

ATC)M587 CG PRO A 82 8.673 -36.763-8.031 1.00 34.39 C

ATC)M588 CD PRO A 82 8.116 -38.144-7.863 1.00 33.30 C

ATOM 589 N THR A 83 6.721 -38.615-11.2371.00 35.91 N

ATOM 590 CA THR A 83 Ei.464 -39.106-12.5771.00 36.20 C

ATOM 591 C THR A 83 5.013 -39.520-12.8321.00 37.20 C

ATOM 592 0 THR A 83 4.671 '39.958-13.9331.00 35.11 0 ATOM 593 CB THR A 83 7.398 '40.276-12.8881.00 36.28 C

ATOM 594 OG1THR A 83 7.299 -41.248-11.8451.00 37.43 0 ATOM 595 CG2THR A 83 8.843 -39.792-12.9671.00 37.12 C

ATOM 596 N LEU A 84 4.162 -39.368-11.8211.00 36.35 N

ATOM 597 CA LEU A 84 2.754 -39.722-11.9601.00 35.59 C

ATOM 598 C LEU A 84 1.972 -38.591-12.6021.00 36.35 C

ATOM 599 0 LEU A 84 2.401 -37.438-12.6011.00 35.86 0 ATOM 600 CB LEU A 84 2.130 -90.035-10.5951.00 34.16 C

ATOM 601 CG LEU A 84 2.593 -41.300-9.870 1.00 35.38 C

ATOM 602 CD1LEU A 84 1.978 -41.353-8.482 1.00 34.22 C

ATOM 603 CD2LEU A 84 2.197 -42.524-10.6831.00 34.98 C

ATOM 604 N LYS A 85 0.824 -38.940-13.1651.00 36.43 N

ATOM 605 CA LYS A 85 -0.060 -37.965-13.77$1.00 37.26 C

ATOM 606 C LYS A 85 -1.480 -38.295-13.3491.00 36.22 C

ATOM 607 0 LYS A 85 -1.789 -39.443-13.0241.0037.15 O

ATO;~I608 CB LYS A 85 0.061 -3'7.999-15.3081.0038.50 C

ATOM 609 CG LYS A 85 0.477 -39.338-15.8841.0041.61 C

ATOM 610 CD LYS A 85 0.683 -39.250-17.3941.0043.64 C

ATOM 611 CE LYS A 85 1.317 -40.522-17.9431.0045.26 C

ATOM 612 NZ LYS A 85 0.542 -41.747-17.5921.0049.29 N

ATOM 613 N VAL A 86 -2.337 -37.285-13.3101.0035.67 N

ATOM 614 CA VAL A 86 -3.719 -37.508-12.9331.0036.32 C

ATOM 615 C VAL A 86 -4.252 -38.566-13.8921.0035.80 C

ATOM 616 0 VAL A 86 -3.923 -38.551-15.0771.0035.85 O

ATOM 617 CB VAL A 86 -4.541 -36.216-13.0701.0036.30 C

ATOM 618 CG1VAL A 86 -5.977 -36.459-12.6471.0035.73 C

ATOM 619 CG2VAL A 86 -3.917 -35.126-12.2071.0036.66 C

ATOM 620 N GLY A 87 -5.048 -39.501-13.3831.0034.68 N

ATOM 621 CA GLY A 87 -5.578 -40.534-14.2521.0032.50 C

ATOM 622 C GLY A 87 -4.781 -41.821-14.1941.0032.16 C

ATOM 623 O GLY A 87 -5.255 -42.863-14.6471.0032.01 0 ATOM 624 N ASP A 88 -3.564 -41.760-13.6621.0030.79 N

ATOM 625 CA ASP A 88 -2.761 -42.968-13.5901.0031.04 C

ATOM 626 C ASP A 88 -'.431 -43.810-12.4691.0028.78 C

ATOM 627 O ASP A 88 -4.137 -43.285-11.6121.0027.00 O

ATOM 628 CB ASP A 88 -1..327-42.658-13.1001.0032.08 C

ATOM 629 CG ASP A 88 -0.431 -92.292-14.2511.0035.69 C

ATOM 630 OD1ASP A 88 -0.770 -92.528-15.4181.0036.06 0 ATOM 631 OD2ASP A 88 0.631 -91.642-13.9791.0036.28 O

ATOM 632 N ILE A 89 -3.213 -45.117-12.5241.0029.91 N

ATOM 633 CA ILE A 89 -3.799 -46.022-11.5491.0028.34 C

ATOM 634 C ILE A 89 -2.668 -46.712-10.8111.0027.28 C

ATOM 635 0 ILE A 89 -1.909 -47.472-11.4091.0029.71 0 ATOM 636 CB ILE A 89 -4.675 -47.099-12.2391.0029.76 C

ATOM 637 CG1ILE A 89 -5.696 -46.442-13.1751.0029.83 C

ATOM 638 CG2ILE A 89 -5.389 -47.923-11.1821.0027.98 C

ATOM 639 CD1ILE A 89 -6.548 -45.375-12.5281.0030,48 C

ATOM 640 N VAL A 90 -2.534 -46.492-9.517 1.0026.81 N

ATOM 641 CA VAL A 90 -1.475 -47.078-8.748 1.0025.86 C

ATOM 642 C VAL A 90 -1.953 -48.372-8.120 1.0025.60 C

ATOM 643 0 VAL A 90 -3.085 -98.471-7.643 1.0024.06 0 ATOM 644 CB VAL A 90 -0.935 -46.160-7.635 1.0027.26 C

ATOM 645 CG1VAL A 90 -0.329 -44.908-8.257 1.0027.19 C

ATO1K646 CG2VAL A 90 -2.036 -45.811-6.657 1.0028.92 C

ATOM 647 N VAL A 91 -1.084 -49.371-8.148 1.0024.05 N

AT01H648 CA VAL A 91 --1.389-50.670-7.574 1.0025.98 C

ATOM 649 C VAL A 91 -0.373 -50.872-6.472 1.0026.55 C

ATOM 650 0 VAL A 91 0.832 -50.767-6.696 1.0026.21 0 ATOM 651 CB VAL A 91 -1.252 -51.799-8.610 1.0024.64 C

ATOM 652 CG1VAL A 91 -1.476 -53.145-7.937 1.0023,64 C

ATOM 653 CG2VAL A 91 -2.270 -51.592-9.732 1.0025.08 C

ATOM 654 N SER A 92 -0.872 -51.147-5.277 1.0025.95 N

ATOM 655 CA SER A 92 -0.025 -51.330-4.115 1.0027.98 C

ATOM 656 C SER A 92 0.784 -52.617-4.111 1.0029.65 C

ATOM 657 0 SER A 92 0.259 -53.681-4.940 1.0028.60 0 ATOM 658 CB SER A 92 -0.889 -51.337-2.859 1.0028.27 C

ATOM 659 OG SER A 92 -1.726 -52.496-2.850 1.0026.89 0 ATOM 660 N ASP A 93 2.063 -52.520-3.754 1.0028.66 N

ATCM 661 CA ASP A 93 2.858 -53.726-3.595 1.0029.57 C

ATOM 662 C ASP A 93 2.808 -53.905-2.077 1.0029.18 C

ATOM 663 0 ASP A 93 2.890 '55.019-1.556 1.0029.63 0 ATOM 664 CB ASP A 93 4.298 -53.567-4.117 1.0031.06 C

ATOM 665 CG ASP A 93 4.993 -52.319-3.607 1.0034.70 C

ATOM 666 OD1ASP A 93 4.398 -51.553-2.825 1.0034.41 0 ATOM 667 OD2ASP A 93 6.156 -52.103-4.007 1.0038.53 O

ATC)M668 N GLU A 94 2.634 -52.785-1.375 1.0028.39 N

ATOM 669 CA GLU A 94 2..510 -52.7760.084 I.0028.89 C

ATOM 670 C GLU A 94 1.921 -51.4960.557 1.0027.17 C

ATOM 671 0 GLU A 94 1.901 -50.463-0.189 1.0026.56 0 ATOM 672 CB GLU A 94 3.865 -53.0170.776 1.0029.42 C

ATOM 673 CG GLU A 94 4.894 -51.9230.592 1.0035.01 C

ATOM 674 CD GLU A 94 6.103 -52.0821.516 1.0036.21 C

ATOM 675 OE1GLU A 94 7.040 -51.2671.412 1.0040.33 0 ATC)M676 OE2GLU A 94 6.119 -53.0092.350 1.0037.31 0 ATOM 677 N ALA A 95 1.437 -51.4281.797 1.0026.91 N

ATOM 678 CA ALA A 95 0.852 -50.2282.383 1.0025.55 C

ATOM 679 C ALA A 95 1.419 -50.0043.778 1.0025.70 C

ATOM 680 O ALA A 95 1.615 -50.9554.536 1.0025.27 0 ATOM 681 CB ALA A 95 -0.668 -50.3722.449 1.0026.35 C

ATOM 682 N ARG A 96 1.692 -48.7474.112 1.0025.40 N

ATOM 683 CA ARG A 96 2.232 -48.3915.421 1.00 25.03 C

ATOM 684 C ARG A 96 1.501 -4'7.1685.968 1.00 25.37 C

ATOM 685 O ARG A 96 0.899 -46.3995.209 1.00 24.62 O

ATOM 686 CB ARG A 96 3.730 -48.0675.319 1.00 26.42 C

ATOM 687 CG ARG A 96 4.645 -49.2434.980 1.00 26.97 C

ATOM 688 CD ARG A 96 6.058 -48.7494.622 1.00 29.18 C

ATOM 689 NE ARG A 96 6.958 -49.8454.261 1.00 31.77 N

ATOM 690 CZ ARG A 96 7.938 -50.3075.035 1.00 39,55 C

ATOM 691 NH1ARG A 96 8.161 -49.7676.230 1.00 35.01 N

ATOM 692 NH2ARG A 96 8.696 -51.3174.618 1.00 33.79 N

ATOM 693 N TYR A 97 1.544 -47.0057.287 1.00 23.79 N

ATOM 694 CA TYR A 97 0.925 -45.8607.949 1.00 25.07 C

ATOM 695 C TYR A 97 1.975 -44.7567.963 1.00 25.70 C

ATCM 696 0 TYR A 97 3.079 -94.9638.468 1.00 26.83 0 ATOM 697 CB TYR A 97 0.576 -46.1939.399 1.00 24.07 C

ATOM 698 CG TYR A 97 -0.563 -47.1669.592 1.00 24.70 C

ATGM 699 CD1TYR A 97 -0.380 -48.33710.3301.00 23.46 C

ATOM 700 CD2TYR A 97 -1..838 -46.8909.093 1.00 22.44 C

ATOM 701 CE1TYR A 97 -1..447 -49.21110.5741.00 23.81 C

ATOM 702 CE2TYR A 97 -2.912 -47.7619.329 1.00 24.23 C

ATOM 703 CZ TYR A 97 -2.706 -48.91710.0741.00 23.68 C

ATOM 704 OH TYR A 97 -3.763 -99.77010.3361.00 25.32 0 ATOM 705 N HIS A 9$ 1.657 -43.5857.427 1.00 26.57 N

ATOM 706 CA HIS A 98 ?..652 -42.5277.440 1.00 25.83 C

ATOM 707 C HIS A 98 2.567 -41.7348.732 1.00 26.50 C

ATOM 708 0 HIS A 98 3.448 -40.9239.026 1.00 27.76 0 ATOM 709 CB HIS A 98 2.512 -41.6086.208 1.00 23.77 C

ATOM 710 CG HIS A 98 1.275 -40.7596.197 1.00 24.01 C

ATOM 711 ND1HIS A 98 1.006 -39.8197.168 1.00 22.25 N

ATOM 712 CD2HIS A 98 0.257 -40.6805.305 1.00 24.45 C

ATOM 713 CE1HIS A 98 -0.123 -39.1966.876 1.00 22.96 C

ATOM 714 NE2HIS A 98 -0.599 -39.6995.751 1.00 23.80 N

ATOM 715 N ASP A 99 1.529 -41.9989.526 1.00 26.70 N

ATOM 716 C;AASP A 99 1.347 -41.28610.7891.00 26.77 C

ATOM 717 C ASP A 99 1.477 -42.14812.0441.00 27.69 C

ATOM 718 0 ASP A 99 1.012 -91.76213.1121.00 28.49 0 ATOM 719 CB ASP A 99 -0.006 -40.55310.8091.00 26.44 C

ATOM 720 CG ASP A 99 -1.208 '41.49310.7131.00 26.73 C

ATOM 721 OD1ASP A99 -1.028 -42.72410.577 1.00 24.41 0 ATO'.M722 OD2ASP A99 -2.354 -40.98510.771 1.00 24.18 0 ATOM 723 N ALA A100 2.098 -43.31411.925 1.00 26.13 N

ATOM 724 CA ALA A100 2.277 -44.16813.093 1.00 28.78 C

ATOM 725 C ALA A100 3.731 -44.09013.537 1.00 29.02 C

ATOM 726 0 ALA A100 4.642 -44.13712.717 1.00 27.79 0 ATOM 727 CB ALA A100 1.947 -45.62412.752 1.00 28.82 C

ATOM 728 N ASP A101 3.946 -43.81114.830 1.00 29.64 N

ATOM 729 CA ASP A101 5.301 -43.65215.344 1.00 28.90 C

ATOM 730 C ASP A101 5.508 -44.20516.747 1.00 29.31 C

ATOM 731 0 ASP A101 5.100 -43.60517.746 1.00 25.74 0 ATOM 732 CB ASP A101 5.694 -42.17515.312 1.00 29.95 C

ATOM 733 CG ASP A101 7.107 -41.92615.813 1.00 31.93 C

ATOM 734 OD1ASP A101 7.558 -40.76915.728 1.00 34.37 0 ATOM 735 OD2ASP A101 7.768 -42.87016.295 1.00 32.97 0 ATOM 736 N VAL A102 6.151 -45.36216.810 1.00 29.67 N

ATOM 737 CA VAL A102 6.463 -46.00318.079 1.00 32.25 C

ATGM 738 C VAL A102 7.969 -46.31018.028 1.00 32.33 C

ATOM 739 0 VAL A102 8.458 -47.25518.638 1.00 30.29 0 ATOM 740 CB VAL A102 5.632 -47.29818.272 1.00 32.52 C

ATOM 741 CG1VAL A102 5.895 -47.89719.641 1.00 34.05 C

ATOM 742 CG2VAL A102 4.149 -96.97718.146 1.00 35.86 C

ATOM 743 N THR A103 8.689 -45.47217.287 1.00 34.36 N

ATOM 749 CA THR A103 10.136 -45.60417.123 1.00 36.32 C

ATOM 745 C THR A103 10.867 -45.54618.462 1.00 38.33 C

ATOM 746 0 THR A103 11.939 -46.13318.615 1.00 38.89 0 ATOM 747 CB THR A103 10.691 -44.48716.214 1.00 35.90 C

ATOM 748 OG1THR A103 10.365 -43.20816.774 1.00 34.98 0 ATOM 749 CG2THR A103 10.088 -44.58514.822 1.00 35.85 C

ATOM 750 N ALA A104 10.290 -44.83319.425 1.00 39.55 N

ATOM 751 CA ALA A104 10.888 -44.71620.750 1.00 41.48 C

ATOM 752 C ALA A104 11.091 -46.09621.378 1.00 43.27 C

ATOM 753 0 ALA A104 11.851 -46.24222.335 1.00 44.82 0 ATOM 754 CB ALA A104 10.006 -43.85721.649 1.00 40.64 C

ATOM 755 N PHE A105 10.418 -47.11020.843 1.00 43.24 N

ATOM 756 CA PHE A105 10.564 -48.45521.378 1.00 43.62 C

ATOM 757 C PHE A105 11.204 -49.43520.404 1.00 43.43 C

ATOM 758 0 PHE A105 10.987 -50.64420.497 1.00 42.16 0 ATOM 759 CB PHE A 105 9.215 -48.99821.850 1.00 44.79 C

ATOM 760 CG PHE A 105 8.659 -48.26923.037 1.00 47.27 C

ATOM 761 CD1PHE A 105 8.002 -47.05422.879 1.00 47.91 C

ATOM 762 CD2PHE A 105 8.832 -48.77424.320 1.00 48.18 C

ATOM 763 CE1PHE A 105 7.527 -46.35123.981 1.00 49.39 C

ATOM 764 CE2PHE A 105 8.360 -48.07725.432 1.00 49.60 C

ATOM 765 CZ PHE A 105 7.707 -46.86425.261 1.00 49.64 C

ATOM 766 N GLY A 106 11.987 -48.90419.468 1.00 43.33 N

ATOM 767 CA GLY A 106 12.683 -49.74818.511 1.00 42.98 C

ATOM 768 C GLY A 106 11.950 -50.12017.237 1.00 42.67 C

ATOM 769 0 GLY A 106 12.520 '50.77816.365 1.00 43.13 0 ATOM 770 N TYR A 107 10.693 -49.71017.113 1.00 40.70 N

ATOM 771 CA TYR A 107 9.926 -50.03315.919 1.00 38.65 C

ATOM 772 C TYR A 107 1Ø319 -49.13214.765 1.00 37.77 C

ATOM 773 0 TYR A 107 10.746 -47.99614.967 1.00 38.72 0 A7.'OM774 CB TYR A 107 8.428 -49.89116.197 1.00 37.89 C

ATOM 775 CG TYR A 107 7.886 -50.95317.121 1.00 36.33 C

ATOM 776 CD1TYR A 107 7.615 -52.23516.654 1.00 35.93 C

A'.COM777 CD2TYR A 107 7.669 -50.68318.470 1.00 36.07 C

ATOM 778 CE1TYR A 107 7.140 -53.22517.507 1.00 35.99 C

ATOM 779 CE2TYR A 107 '7.196 -51.66719.333 1.00 35.35 C

ATOM 780 CZ TYR A 107 6.933 -52.93218.842 1.00 36.03 C

ATOM 781 OH TYR A 107 6.452 -53,90219.687 1.00 38.62 0 ATOM 782 N GLU A 108 10.190 -49.65913.554 1.00 36.76 N

ATOM 783 CA GLU A 108 10.497 -48.90812.346 1.00 36.37 C

ATOM 784 C GLU A 108 9.432 -47.81912.225 1.00 35.27 C

ATOM 785 0 GLU A 108 8.309 -97.99612.703 1.00 34.93 0 ATOM 786 CB GLU A 108 10.494 -49.84611.140 1.00 37.97 C

ATOM 787 CG GLU A 108 10.490 -49.1569.800 1.00 42.35 C

ATOM 788 CD GLU A 108 10.756 -50.115$.653 1.00 44.37 C

ATOM 789 OE1GLU A 108 1Ø722 -49.6567.491 1.00 46.05 0 ATOM 790 OE2GLU A 108 11.006 -51.3178.911 1.00 44.53 0 ATOM 791 N TYR A 109 9.771 -46.69211.608 1.00 32.95 N

ATOM 792 CA TYR A 109 8.787 -45.63111.478 1.00 32.17 C

ATOM 793 C TYR A 109 7.572 -46.11910.690 1.00 30.48 C

ATOM 799 0 TYR A 109 7.716 -46.7499.641 1.00 29.16 0 :ATOM795 CB TYR A 109 9.375 -44.40310.780 1.00 33.78 C

ATOM 796 CG TYR A 109 8.413 -43.24010.828 1.00 35.32 C

ATC)M797 CD1TYR A109 8.327 -42.42911.961 1.0034.64 C

ATOM 798 CD2TYR A109 7.500 -43.0289.795 1.0034.63 C

ATOM 799 CE1TYR A109 '7.348 -41.44012.066 1.0036.19 C

ATOM 800 CE2TYR A109 6.518 -42.0499.892 1.0035.30 C

ATOM 801 CZ TYR A109 6.445 -41.26111.030 1.0035.86 C

ATOM 802 OH TYR A109 5.452 -40.31311.137 1.0036.66 O

ATOM 803 N GLY A110 6.379 -45.83111.206 1.0029.10 N

ATOM 804 CA GLY A110 5.156 -46.24010.536 1.0029.13 C

ATOM 805 C GLY A110 4.645 -47.59010.987 1.0028.78 C

ATOM 806 0 GLY A110 3.485 -47.93910.755 1.0028.57 0 ATOM 807 N GLN A111 5.512 -48.35611.640 1.0030.11 N

ATOM 808 CA GLN A111 5.149 -49.68512.120 1.0030.49 C

ATOM 809 C GLN A111 4.504 -49.65113.502 1.0030.79 C

ATOM 810 O GLN A111 4.953 -48.92614.395 1.0030.17 0 ATOM 811 CB GLN A111 6.396 -50.58312.141 1.0031.83 C

ATOM 812 CG GLN A111 6.205 -51.94512.805 1.0032.25 C

ATOM 813 CD GLN A111 7.446 -52.82212.699 1.0033.42 C

ATOM 814 OE1GLN A111 8.570 '52.35712.908 1.0032.42 0 ATOM 815 NE2GLN A111 7,246 -54.09912.384 1.0034.58 N

ATOM 816 N LEU A112 3.439 -50.43213.664 1.0029.13 N

A7.'OM817 CA LEU A112 2.732 -50.52714.934 1.0030.51 C

ATOM 818 C LEU A112 3.058 -51.85915.589 1.0030.32 C

ATOM 819 0 LEU A112 3.252 -52.85619.905 1.0031.26 O

A'.COM820 CB LEU A112 1.218 -50.42214.721 1.0029.91 C

A'POM821 CG LEU A112 0.692 -49.00814.466 1.0029.96 C

A'POM822 CD1LEU A112 -0.814 -49.04414.291 1.0027.95 C

ATOM 823 CD2LEU A112 1.065 -48.11915.647 1.0029.10 C

ATOM 824 N PRO A113 3.135 -51.88816.927 1.0031.57 N

ATOM 825 CA PRO A113 3.441 -53.11317.669 1.0032.90 C

ATOM 826 C PRO A113 2.529 -54,26317.263 1.0034.84 C

ATOM 827 O PRO A113 1.306 -54.11517.232 1.0036.63 O

ATOM 828 CB PRO A113 3.234 -52.69519.112 1.0031.93 C

ATOM 829 CG PRO A113 3.661 -51.26419.097 1.0031.19 C

ATOM 830 CD PRO A113 2.991 -50.75017.852 1.0030.96 C

P.TOM831 N GLY A114 3.130 -55.40516.949 1.0035.84 N

ATOM 832 CA GLY A114 2.353 -56.56916.563 1.0037.05 C

ATOM 833 C GLY A114 2.054 -56.64015.079 1.0037.56 C

ATOM 834 O GLY A114 1.311 -57.51914.690 1.0038.66 0 ATOM 835 N CYSA 115 2.633 -55.72514.305 1.0036.31 N

ATOM 836 CA CYSA 115 2.419 -55.68812.860 1.0035.65 C

ATOM 837 C CYSA 115 3.731 -55.63412.105 1.0034.97 C

ATOM 838 0 CYSA 115 4.763 -55.25312.656 1.0034.40 0 ATOM 839 CB CYSA 115 1.644 -59.43312.446 1.0034.62 C

ATOM 840 SG CYSA 115 0.068 -54.15413.229 1.0036.05 S

ATOM 841 N PROA 1I6 :3.710 -56.02810.825 1.0034.35 N

ATOM 842 CA PROA 116 4.997 -55.96710.047 1.0034.30 C

ATOM 843 C PROA 116 5.136 -54.4759.759 1.0033.36 C

ATOM 844 0 PROA 116 4.209 -.'i3.6809.969 1.0032.85 0 ATOM 845 CB PROA 116 4.613 -56.7898.803 i.0034.44 C

ATc7M846 CG PROA 116 3.128 -56.6028.660 1.0034.67 C

ATOM 847 CD PROA 116 2.651 -56.73010.081 1.0035.06 C

ATOM 848 N ALAA 117 6.316 -54.0779.294 1.0032.85 N

ATOM 849 CA ALAA 117 6.557 -52.6629.013 1.0031.88 C

ATOM 850 C ALAA 117 5.586 -52.1497.948 1.0032.34 C

ATOM 851 0 ALAA 117 5.138 -51.0007.995 1.0032.20 O

ATOM 852 CB ALAA 117 7.989 -52.4568.563 1.0031.53 C

ATOM 853 N GLYA 118 5.273 -53.0136.989 1.0031.42 N

ATOM 854 CA GLYA 118 4.347 -52.6645.928 1.0030.78 C

ATOM 855 C GLYA 118 3.458 -53.8675.669 1.0030.71 C

ATOM 856 0 GLYA 118 3.844 -54.9935.982 1.0029.46 0 ATOM 857 N PHEA 119 2.266 -53.6395.123 1.0029.91 N

ATOM 858 CA PHEA 119 1.336 -54.7314.820 1,0029.54 C

ATOM 859 C PHEA 119 1.428 -55.0333.326 1.0029.29 C

ATOM 860 0 PHEA 119 1.166 '54.1652.488 1.0028.39 0 ATOM 861 CB PHEA 119 -0.087 -54.3265.206 1.0027.97 C

A7.'OM862 CG PHEA 119 -0.251 -54.0446.670 1.0030.53 C

ATOM 863 CD1 PHEA 119 -0.391 -55.0877.583 1.0028.46 C

A".'OM864 CD2 PHEA 119 -0.229 -52.7397.147 1.0029.36 C

A'.COM865 CE1 PHEA 119 -0.504 -54.8338.948 1.0029.48 C

A'COM866 CE2 PHEA 119 --0.342 -52.4738.508 1.0031.49 C

ATOM 867 CZ PHEA 119 ~-0.480 -53.5289.915 1.0028.17 C

ATOM 868 N LYSA 120 1.806 -56.2652.996 1.0029.30 N

A'rOM869 CA LYSA 120 1.982 --56.6611.602 1.0029.46 C

A'rOM870 C LYSA 120 0.799 -57.1340.851 1.0028.96 C

ATOM 871 O LYSA 120 -0.008 -57.9831.328 1.0028.17 0 ATOM 872 CB LYSA 120 3.061 -57.7401.504 1.0032.54 C

ATOM 873 CG LYSA 120 9.440 -57.2651.909 1.00 39.90 C

ATOM 874 CD LYSA 120 5.506 -58.3251.622 1.00 44.51 C

ATOM 875 CE LYSA 120 6.904 -57.7921.929 1.00 47.43 C

ATOM 876 NZ LYSA 120 7.201 -56.5501.149 1.00 48.57 N

ATOM 877 N ALAA 121 0.556 -56.572-0.3371.00 28.84 N

ATC>M878 CA ALAA 121 -0.558 -56.942-1.1931.00 29.69 C

ATOM 879 C ALAA 121 -0.201 -58.309-1.7831.00 30.51 C

ATOM 880 0 ALAA 121 0.973 -58.657-1.8791.00 30.33 O

ATUM 881 CB ALAA 121 -0.733 -55.910-2.3031.00 27.72 C

ATUM 882 N ASPA 122 -1.214 -59.065-2.1711.00 32.27 N

ATOM 883 CA ASPA 122 -1.010 -60.397-2.7271.00 34.18 C

ATOM 884 C ASPA 122 -0.428 -60.312-4.1341.00 34.54 C

ATOM 885 0 ASPA 122 -0,916 -59.547-4.9651.00 34.08 0 ATOM 886 CB ASPA 122 -2.347 -61.135-2.7561.00 36.03 C

ATOM 887 CG ASPA 122 -2.201 -62.601-3.1011.00 38.71 C

AT(JM888 OD1 ASPA 122 -1.748 -63.382-2.2321.00 37.82 0 ATcJM889 OD2 ASPA 122 -2.544 -62.969-4.2451.00 39.77 0 ATOM 890 N ASPA 123 0.612 '61.101-4.3991.00 34.63 N

ATOM 891 CA ASPA 123 1.271 -61.111-5.7071.00 35.21 C

ATOM 892 C ASPA 123 0.340 -61.397-6.8811.00 33.59 C

ATOM 893 0 ASPA 123 0.455 -60.779-7.9411.00 32.73 O

ATOM 894 CB ASPA 123 2.403 -62.143-5.7261.00 37.99 C

ATOM 895 CG ASPA 123 3.669 -61.642-5.0591.00 41.80 C

ATOM 896 OD1 ASPA 123 4.571 -62.470-4.8181.00 45.63 0 ATOM 897 OD2 ASPA 123 3.775 -60.427-4.7861.00 43.59 0 ATOM 898 N LYSA 124 -0.570 -62.346-6.7011.00 32.95 N

ATOM 899 CA LYSA 124 -1.494 -62.703-7.7671.00 33.21 C

ATOM 900 C LYSA 129 -2.484 -61.577-8.0361.00 31.42 C

ATOM 901 0 LYSA 124 -2.769 -61.252-9.1871.00 31.66 O

ATOM 902 CB LYSA 124 -2.250 -63.984-7.3991.00 37.08 C

ATOM 903 CG LYSA 124 -3.212 -64.475-8.4721.00 40.34 C

ATOM 904 CD LYSA 124 -4.081 -65.608-7.9441.00 44.75 C

ATOM 905 CE LYSA 124 -5.250 -65.898-8.8811.00 47.58 C

ATOM 906 NZ LYSA 124 -6.220 -66.864-8.2841.00 50.57 N

ATOM 907 N LEUA 125 -3.007 -60.975-6.9751.00 29.19 N

ATOM 908 CA LEUA 125 -3.966 -59.893-7.1391.00 27.63 C

A'~OM909 C LEUA 125 -3.307 -58.703-7.8341.00 28.66 C

ATOM 910 0 LEUA 125 -3.903 -58.076-8.7101.00 29.47 0 ATOM 911 CB LEUA 125 -4.535 -59.488-5.777 1.00 25.90 C

ATOM 912 CG LEUA 125 -5.282 -60.595-5.023 1.00 24.90 C

ATOM 913 CD1 LEUA 125 -5.888 -60.042-3.753 1.00 26.06 C

ATOM 914 CD2 LEUA 125 -6.378 -61.175-5.901 1.00 25.35 C

ATOM 915 N ILEA 126 -2.071 -58.404-7.446 1.00 28.46 N

ATOM 916 CA ILEA 126 -1.317 -57.305-8.037 1.00 27.94 C

ATOM 917 C ILEA 126 -1.194 -57.511-9.545 1.00 29.22 C

ATOM 918 0 ILEA 126 -1.468 -56.609-10.3391.00 27.72 0 ATOM 919 CB ILEA 126 0.108 -57.225-7.443 1.00 28.01 C

ATOM 920 CG1 ILEA 126 0.049 '56.733-5.993 1.00 27.27 C

ATOM 921 CG2 ILEA 126 0.981 -56.314-8.304 1.00 27.53 C

ATOM 922 CD1 ILEA 126 1.390 -56.821-5.260 1.00 28.34 C

ATOM 923 N ALAA 127 -0.767 -58.707-9.935 1.00 29.54 N

ATOM 924 CA ALAA 127 -0.599 -59.031-11.3431.00 28.86 C

ATC)M925 C ALAA 127 -1.912 -58.952-12.1101.00 28.83 C

ATOM 926 0 ALAA 127 -1.968 -58.382-13.1951.00 29.37 0 ATOM 927 CB ALAA 127 0.005 -60.428-11.4821.00 30.81 C

ATOM 928 N ALAA 128 -2.970 -59.530-11.5521.00 28.67 N

ATOM 929 CA ALAA 128 -4.264 -59.511-12.2201.00 28.71 C

ATOM 930 C ALAA 128 -4.773 -58.073-12.3721.00 27.51 C

ATOM 931 0 ALAA 128 -5.295 -57.700-13.4201.00 27.87 0 ATOM 932 CB ALAA 128 -5.271 -60,360-11.4341.00 28.00 C

ATOM 933 N ALAA 129 -4.616 -57.267-11.3271.00 26.93 N

ATOM 934 CA ALAA 129 -5.055 -55.880-11.3781.00 26.44 C

ATOM 935 C ALAA 129 -4.295 -55.128-12.4761.00 28.05 C

ATOM 936 0 ALAA 129 -4.895 -54.418-13.2901.00 26.50 0 ATOM 937 CB ALAA 129 -4.833 -55.212-10.0221.00 25.94 C

ATOM 938 N GLUA 130 -2.975 -55.290-12.4981.00 29.44 N

ATOM 939 CA GLUA 130 -2.140 -54.632-13.5021.00 31.81 C

ATOM 940 C GLUA 130 -2.533 -55.038-14.9201.00 32.45 C

ATOM 941 0 GLUA 130 -2.481 -54.226-15.8431.00 31.23 0 ATOM 942 CB GLUA 130 -0.663 -54.952-13.2511.00 33.31 C

ATOM 943 CG GLUA 130 -0.029 -54.071-12.1811.00 36.56 C

ATOM 944 CD GLUA 130 1.371 -54.513-11.7801.00 39.40 C

ATOM 945 OE1 GLUA 130 2.083 -53.699-11.1471.00 39.55 0 ATOM 946 OE2 GLUA 130 1.757 -55.667-12.0791.00 38.99 O

ATOM 947 N ALAA 131 -2.935 -56.294-15.0901.00 32.47 N

ATOM 948 CA ALAA 131 -3.347 -56.785-16.3991.00 33.21 C

ATOM 949 C ALAA 131 -4.702 '56.193-16.7921.00 33.65 C

ATOM 950 0 ALAA 131 -4.913 -55.813-17.9441.00 33.55 O

ATOM 951 CB ALAA 131 -3.918 -58.312-16.3871.00 33.70 C

ATOM 952 N CYSA 132 -5.622 -56.112-15.8351.00 33.54 N

ATOM 953 CA CYSA 132 -6.944 -55.556-16.1141.00 32.72 C

ATOM 954 C CYSA 132 -6.849 '54.081-16.4661.00 32.83 C

ATOM 955 0 CYSA 132 -7.594 -53.589-17.3211.00 33.45 0 ATOM 956 CB CYSA 132 -7.870 -55.735-14.9121.00 32.73 C

ATOM 957 SG CYSA 132 -8.426 -57.438-14.6791.00 34.51 S

ATOM 958 N ILEA 133 -5.931 -53.378-15.8071.00 30.60 N

ATOM 959 CA ILEA 133 -5.743 -51.960-16.0631.00 29.50 C

ATOM 960 C ILEA 133 -5.189 -51.739-17.4711.00 29.68 C

ATOM 961 0 ILEA 133 -5.663 -50.869-18.2031.00 29.99 0 ATC>M962 CB ILEA 133 -4.802 -51.332-15.0081.00 28.01 C

ATOM 963 CG1 ILEA 133 -5.491 -51.360-13.6411.00 26.49 C

ATOM 964 CG2 ILEA 133 -4.439 -99.900-15.4021.00 28.18 C

ATOM 965 CD1 ILEA 133 -4.556 -51.143-12.4691.00 25.48 C

ATOM 966 N ALAA 134 -4.197 -52.530-17.8591.00 29.83 N

ATOM 967 CA ALAA 134 -3.624 -52.388-19.1941.00 31.84 C

ATOM 968 C ALAA 134 -4.666 -52.710-20.2701.00 31.71 C

ATOM 969 O ALAA 134 -4.726 -52.048-21.2971.00 30.84 0 ATOM 970 CB ALAA 134 -'x.404 -53.302-19.3501.00 30.64 C

ATOM 971 N GLUA 135 -5.497 -53.718-20.0271.00 33.64 N

ATOM 972 CA GLUA 135 -6.519 -54.104-20.9951.00 34.62 C

ATOM 973 C GLUA 135 -7.518 -52.992-21.2631.00 34.02 C

ATOM 974 0 GLUA 135 -8.140 -52.954-22.3271.00 34.38 0 ATc)M975 CB GLUA 135 -7.246 -55.361-20.5171.00 36.58 C

ATOM 976 CG GLUA 135 -6.357 -56.594-20.5281.00 41.70 C

ATOM 977 CD GLUA 135 -7.025 -57.818-19.9251.00 44.04 C

ATOM 978 OE1 GLUA 135 -6.370 -58.8$1-19.8781.00 44.66 O

ATOM 979 OE2 GLUA 135 -8.198 -57.718-19.4971.00 45.58 0 ATOM 980 N LEUA 136 -7.677 -52.094-20.2971.00 32.28 N

ATOM 981 CA LEUA 136 -8.589 -50.967-20.9351.00 32.18 C

ATOM 982 C LEUA 136 -7.832 -99.780-21.0311.00 32.05 C

ATOM 983 0 LEUA 136 -8.362 -48.662-21.1231.00 30.78 O

ATOM 984 CB LEUA 136 -9.167 -50.579-19.0681.00 32.83 C

ATOM 985 CG LEUA 136 -10.115 -51.577-18.3921.00 34.44 C

ATOM 986 CD1 LEUA 136 -10.415 -51.128-16.9681.00 34.64 C

ATOM987 CD2LEU A136 -11.404 -51.676-19.1891.0034.51 C

ATOM988 N ASN A137 -6.590 -50.032-21.4341.0030.53 N

ATOM989 CA ASN A137 -5.742 -48.998-22.0281.0032.25 C

ATOM990 C ASN A137 -5.907 -47.901-21.0261.0032.09 C

ATOM991 0 ASN A137 -5.251 -46.740-21.3971.0031.43 0 ATOM992 CB ASN A137 -6.430 -48.375-23.2511.0031.09 C

ATOM993 CG ASN A137 -6.676 -49.384-24.3581.0032.88 C

ATOM994 OD1ASN A137 -7.760 -49.429-24.9371.0032.17 0 ATOM995 ND2ASN A137 ~-5.666 -50.192-24.6621.0030.40 N

ATOM996 N LEU A138 -5.302 -48.273-19.7551.0033.21 N

ATOM997 CA LEU A138 -4.969 -47.315-18.7101.0033.06 C

ATOM998 C LEU A138 -3.543 -47.598-18.2581.0033.17 C

ATOM999 O LEU A138 -2.977 -48.638-18.5921.0033.07 0 ATOM1000 CB LEU A138 -5.952 -47.442-17.5421.0032.99 C

ATOM1001 CG LEU A138 -7.412 -47.186-17.9391.0033.72 C

ATOM1002 CD1LEU A138 -8.342 -47.597-16.8081.0035.43 C

ATOM1003 CD2LEU A138 -7.602 -45.714-18.2931.0033.78 C

ATOM1004 N ASN A139 -2.959 -46.673-17.5061.0033.38 N

ATOM1005 CA ASN A139 -1.585 -46.838-17.0521.0033.92 C

ATOM1006 C ASN A139 -1..479 -47.214-15.5841.0033.36 C

ATOM1007 0 ASN A139 -1.875 -46.442-14.7111.0033.74 0 ATOM1008 CB ASN A139 -0.795 -45.549-17.3111.0035.04 C

ATOM1009 CG ASN A139 0.674 -45.689-16.9681.0038.50 C

ATOM1010 OD1ASN A139 1..317 -46.682-17.3261.0039.86 0 ATC>M1011 ND2ASN A139 1..221 -44.690-16.2801.0037.58 N

ATUM1012 N ALA A140 -0.927 -48.397-15.3241.0031.59 N

ATOM1013 CA ALA A140 -0.757 -98.891-13.9631.0032.21 C

ATOM1014 C ALA A140 0.676 -48.697-13.4611.0032.52 C

ATOM1015 0 ALA A140 1.640 -98.988-14.1741.0033.13 0 ATOM1016 CB ALA A140 -1.126 -50.357-13.8961.0032.73 C

ATOM1017 N VAL A141 0.804 -48.206-12.2311.0031.10 N

ATOM1018 CA VAL A191 2.107 -47.980-11.6111.0029.86 C

ATOM1019 C VAL A141 2.110 -48.680-10.2581.0029.31 C

ATOM1020 0 VAL A141 :1.301 -48.352-9.386 1.0028.07 0 ATOM1021 CB VAL A141 2.369 -46.477-11.3881.0030.84 C

ATOM1022 CG1VAL A141 3.764 -46.272-10.7941.0029.73 C

ATOM1023 CG2VAL A141 2.223 -45.726-12.7031.0031.02 C

ATc)M1024 N ARG A142 3.024 -49.629-10.0781.0027.92 N

ATOM1025 CA ARG A192 3.097 -50.389-8.835 1.0028.73 C

ATOM1026 C ARG A142 3.981 -49.716-7.798 1.0028.89 C

ATOM1027 0 ARG A142 4.981 -49.095-8.137 1.0029.83 0 ATOM1028 CB ARG A142 3.629 -51.796-9.115 1.0030.58 C

ATOM1029 CG ARG A142 3.557 -52.724-7.912 1.0033.42 C

ATOM1030 CD ARG A142 4.362 -54.000-8.133 1.0036.76 C

ATOM1031 NE ARG A142 4.002 -54.680-9.373 1.0038.07 N

ATOM1032 CZ ARG A142 4.561 -55.813-9.788 1.0040.15 C

ATOM1033 NH1ARG A142 5.507 -56.391-9.060 1.0039.12 N

ATOM1034 NH2ARG A142 4.176 -56.370-10.9301.0039.12 N

ATOM1035 N GLY A143 3.618 -49.837-6.527 1.0029.01 N

ATOM1036 CA GLY A143 4.436 -99.222-5.502 1.0027.44 C

ATOM1037 C GLY A143 3.810 -49.103-4.127 1.0028.20 C

ATOM1038 0 GLY A143 2.699 -99.583-3.873 1.0027.11 0 ATOM1039 N LEU A144 9.553 -48.453-3.237 1.0027.25 N

ATOM1040 CA LEU A144 9.136 -48.237-1.863 1.0027.70 C

ATOM1041 C LEU A144 3.084 -47.145-1.712 1.0027.12 C

ATOM1042 0 LEU A144 3.242 -46.032-2.213 1.0027.93 0 ATOM1043 CB LEU A144 5.350 -97.879-0.999 1.0026.69 C

ATOM1044 CG LEU A144 5.040 -47.3760.417 1.0025.72 C

ATOM1045 CD1LEU A144 4.295 -48.4451.212 1.0025.10 C

ATC)M1046 CD2LEU A144 6.332 -47.0071.113 1.0026.65 C

ATOM1047 N ILE A145 2.006 -47.480-1.017 1.0026.79 N

ATOM1048 CA ILE A145 0.945 -46.525-0.751 1.0026.51 C

ATC)M1049 C ILE A145 0.947 -96.3330.756 1.0025.96 C

ATOM1050 0 ILE A145 1.055 -47.3051.513 1.0024.62 0 ATOM1051 CB ILE A145 -0.422 -47.063-1.213 1.0028.17 C

ATOM1052 CG1ILE A145 -0.395 -47.252-2.736 1.0030.74 C

ATOM1053 CG2ILE A145 -1.547 -46.099-0.792 1.0026.70 C

ATOM1054 CD1ILE A145 -1.697 -47.899-3.322 1.0034.38 C

ATOM1055 N VAL A146 0.871 -45.0811.193 1.0023.54 N

ATOM1056 CA VAL A146 0.844 -44.7832.614 1.0023.21 C

ATOM1057 C VAL A146 -0.465 -44.0772.939 1.0022.87 C

ATOM1058 0 VAL A146 -1.061 -43.4312.076 1.0023.54 0 ATOM1059 CB VAL A146 2.026 -43.8683.040 1.0024.62 C

ATOM1060 CG1VAL A146 3.361 -44.6132.876 1.0024.85 C

ATOM1061 CG2VAL A146 2.017 -42.5892.215 1.0025.93 C

ATc)M1062 N SER A14? -0.935 -44.2194.168 1.0021.67 N

ATOM1063 CA SER A147 -2.177 -43.5474.534 1.00 23.94 C

ATOM1064 C SER A147 -2.159 -43.0945.978 1.00 20.49 C

ATOM1065 0 SER A147 -1.359 -43.5646.786 1.00 21.37 0 ATOM1066 CB SER A147 -3.388 -44.4544.267 1.00 24.02 C

ATOM1067 OG SER A147 -3.296 -45.6325.016 1.00 29.64 0 ATOM1068 N GLY A148 -3.038 -42.1556.296 1.00 21,84 N

ATOM1069 CA GLY A148 -3.107 -41.6357.644 1.00 22.60 C

ATOM1070 C GLY A148 -4.385 -40.8487.791 1.00 23.10 C

ATGM1071 0 GLY A148 -5.040 -40.5966.792 1.00 24.75 0 ATOM1072 N ASP A149 -4.743 -40.5169.027 1.00 24.22 N

ATGM1073 CA ASP A149 -5.962 -39.7689.281 1.00 24.75 C

ATOM1074 C ASP A149 -5.807 -38.2849.034 1.00 27.87 C

ATOM1075 0 ASP A149 -6.201 -37.4619.850 1.00 27.50 0 ATOM1076 CB ASP A149 -6.445 -40.01210.7051.00 23.01 C

ATOM1077 CG ASP A149 -7.294 -41.25110.8081.00 23.19 C

ATOM1078 OD1ASP A149 -7.693 -41.7659.739 1.00 24.62 0 ATOM1079 OD2ASP A149 -7.578 -41.70211.9361.00 19.98 0 ATOM1080 N ALA A150 -5.256 -37.9447.880 1.00 29.67 N

ATOM1081 CA ALA A150 -5.055 -36.5467.539 1.00 32.31 C

ATOM1082 C ALA A150 -:1.221 -36.3326.051 1.00 33.66 C

ATOM1083 0 ALA A150 -4.865 -37.1895.238 1.00 32.99 0 ATOM1084 CB ALA A150 -3.661 -36.0967.967 1.00 30.97 C

ATOM1085 N PHE A151 -5.798 -35.1975.691 1.00 33.74 N

ATOM1086 CA PHE A151 -5.924 -34.8804.290 1.00 35.87 C

ATOM1087 C PHE A151 -4.689 -3.9.0224.043 1.00 36.77 C

ATOM1088 O PHE A151 -4.606 -32.9024.536 1.00 37.26 O

ATOM1089 CB PHE A151 -7.199 -34.0844.009 1.00 35.66 C

ATOM1090 CG PHE A151 -'1.340 -33.6842.575 1.00 37.83 C

ATOM1091 CD1PHE A151 -7.078 -32.3792.171 1.00 38.95 C

ATOM1092 CD2PHE A151 -'1.672 -34.6281.612 1.00 38.16 C

ATOM1093 CE1PHE A151 -7.141 -32.0240.826 1.00 39.79 C

ATOM1094 CE2PHE A151 -'7.737 -34.2800.263 1.00 39.05 C

ATOM1095 CZ PHE A151 -7.470 -32.978-0.1281.00 38.06 C

ATOM1096 N ILE A152 -3.716 -34.5723.322 1.00 39.11 N

ATOM1097 CA ILE A152 -2.477 -33.8603.023 1.00 41.33 C

ATC)M1098 C ILE A152 -2.767 -32.7362.044 1.00 44.11 C

ATOM1099 O ILE A152 -3.171 -32.9700.905 1.00 45.30 0 ATc7M1100 CB ILE A152 -1.417 -:34.8072.421 1.00 40.67 C

ATOM1101 CG1ILE A152 -1.181 -35.985 3.370 1.0038.45 C

ATOM1102 CG2ILE A152 -0.115 -34.054 2.189 1.0040.51 C

ATCM1103 CD1ILE A152 -0.867 -35.570 4.799 1.0037.82 C

ATCMll04 N ASN A153 -2.546 -31.510 2.497 1.0046.67 N

ATOM1105 CA ASN A153 -2.829 -30.344 1.680 1.0048.95 C

ATOM1106 C ASN A153 -1.603 -29.480 1.396 1.0049.03 C

ATOM1107 0 ASN A153 -1.377 -29.077 0.257 1.0050.43 0 ATOM1108 CB ASN A153 -3.893 -29.501 2.385 1.0050.98 C

ATOM1109 CG ASN A153 -4.677 -28.640 1.429 1.0053.81 C

ATOM1110 OD1ASN A153 -5.376 -27.712 1.843 1.0055.20 O

ATOM1111 ND2ASN A153 -9.577 -28.946 0.138 1.0054.91 N

ATOM1112 N GLY A154 -0.812 -29.204 2.431 1.0048.44 N

ATOM1113 CA GLY A154 0.360 -28.359 2.269 1.0045.14 C

ATOM1114 C GLY A154 1.724 -29.017 2.133 1.0043.26 C

ATOM1115 0 GLY A154 1..890 -30.227 2.304 1.0042.16 0 ATOM1116 N SER A155 2.711 -28.180 1.833 1.0040.52 N

ATOM1117 CA SER A155 4.093 -28.605 1.645 1.0038.45 C

ATOM1118 C SER A155 4.691 -29.350 2.841 1.0036.07 C

ATOM1119 0 SER A155 5.402 -30.340 2.674 1.0036.02 0 ATOM1120 CB SER A155 4.956 -27.377 1.328 1.0038.59 C

ATOM1121 OG SER A155 6.300 -27.743 1.070 1.0041.69 0 ATOM1122 N VAL A156 4.413 -28.865 4.044 1.0034.61 N

ATOM1123 CA VAL A156 4.946 -29.477 5.256 1.0033.94 C

ATOM1124 C VAL A156 4.503 -30.929 5.416 1.0031.68 C

ATOM1125 0 VAL A156 5.315 -31.805 5.735 1.0032.04 0 ATC)M1126 CB VAL A156 4.528 -28.668 6.500 1.0034.81 C

ATOM1127 CG1VAL A156 5.102 -29.300 7.757 1.0035.71 C

ATC)M1128 CG2VAL A156 5.022 -27.240 6.360 1.0037.00 C

ATOM1129 N GLY A157 3.219 -31.180 5.187 1.0029.88 N

ATOM1130 CA GLY A157 2.700 -32.534 5.301 1.0029.61 C

ATOM1131 C GLY A157 3.344 -33.468 4.291 1.0028.41 C

ATOM1132 0 GLY A157 3.677 -34.609 4.607 1.0028.45 0 ATOM1133 N LEU A158 3.516 -32.983 3.066 1.0029.24 N

ATOM1134 CA LEU A158 4.127 -33.770 2.004 1.0028.75 C

ATOM1135 C LEU A158 'i.596 -34.005 2.292 1.0028.35 C

ATOM1136 0 LEU A158 6.108 -35.110 2.079 1.0028.72 0 ATOM1137 CB LEU A158 3.984 -33.051 0.661 1.0031.81 C

ATOM1138 CG LEU A158 2.563 -32.952 0.104 1.0034.36 C

ATOM 1139 CD1LEU A158 2.490 -31.863-0.967 1.0034.64 C

ATOM 1140 CD2LEU A158 2.162 -34.308-0.471 1.0035.14 C

ATOM 1141 N ALA A159 6.275 -32.9702,783 1.0027.98 N

ATOM 1142 CA ALA A159 7.701 -33.0693,088 1.0026.67 C

ATOM 1143 C ALA A159 7.985 -34.1594.107 1.0025.89 C

ATOM 1144 0 ALA A159 8.911 -34.9563.937 1.0026.59 O

ATOM 1145 CB ALA A159 8.224 -31.7373.592 1.0027.38 C

ATOM 1146 N LYS A160 7.190 -34.1885.172 1.0026.99 N

ATOM 1147 CA LYS A160 7.356 -35.1856.220 1.0025.83 C

ATOM 1148 C LYS A160 7.145 -36.5845.656 1.0026.24 C

ATOM 1149 0 LYS A160 7.891 -37.5085.974 1.0024.93 0 ATOM 1150 CB LYS A160 6.358 -34.9407.354 1.0028.66 C

ATOM 1151 CG LYS A160 6.474 -35.9438.485 1.0029.31 C

ATOM 1152 CD LYS A160 5.518 -35.6189.623 1.0033.14 C

ATOM 1153 CE LYS A160 5.642 -36.64010.755 1.0032.20 C

ATOM 1154 NZ LYS A160 4.749 -36.29511.891 1.0032.97 N

ATOM 1155 N ILE A161 6.127 -36.7419.819 1.0026.09 N

ATOM 1156 CA ILE A161 5.855 -38.0444.235 1.0027.73 C

ATOM 1157 C ILE A161 6.978 -38.4923.298 1.0027.11 C

ATOM 1158 O ILE A161 7.441 -39.6293.377 1.0026.56 0 ATOM 1159 CB ILE A161 4.512 -38.0443.468 1.0028.04 C

ATOM 1160 CG1ILE A161 3.352 -37.9184.462 1.0028.64 C

ATOM 1161 CG2ILE A161 4.386 -39.3282.649 1.0027.47 C

ATCM 1162 CD1ILE A161 1.997 -37.7423.819 1.0027.62 C

ATOM 1163 N ARG A162 7.431 -37.6022.421 1.0027.78 N

ATOM 1164 CA ARG A162 8.492 -37.9661.486 1.0028.09 C

ATOM 1165 C ARG A162 9.826 -38.1882.186 1.0028.46 C

ATOM 1166 0 ARG A162 10.677 -38.9301.697 1.0028.37 0 ATOM 1167 CB ARG A162 8.630 -36.9030.394 1.0028.83 C

ATOM 1168 CG ARG A162 7.357 -36.708-0.433 1.0029.07 C

ATOM 1169 CD ARG A162 7.676 -36.631-1.918 1.0029.29 C

ATOM 1170 NE ARG A162 8.245 -37.890-2.378 1.0029.54 N

ATOM 1171 CZ ARG A162 8.927 -38.047-3.507 1.0031.14 C

ATC>M1172 NHlARG A162 9.135 -37.015-4.317 1.0030.27 N

ATOM 1173 NH2ARG A162 9.413 -39.243-3.819 1.0028.93 N

ATC>M1174 N HIS A163 10.010 -37.5583.339 1.0028.87 N

ATOM 1175 CA HIS A163 11.242 -37.7404.091 1.0030.34 C

ATOM 1176 C HIS A163 11.230 -39.1114.759 1.0029.63 C

ATOM1177 0 HIS A163 12.224 -39.8354.732 1.0029.08 0 ATOM1178 CB HIS A163 11.395 -36.6675.170 1.0032.33 C

ATOM1179 CG HIS A163 12.501 -36.9536.136 1.0037.04 C

ATOM1180 ND1 HIS A163 13.832 -36.7955.811 1.0039.78 N

ATOM1181 CD2 HIS A163 12.478 -37.4377.401 1.0038.74 C

ATOM1182 CE1 HIS A163 14.580 -37.1706.835 1.0040.34 C

ATOM1183 NE2 HIS A163 13.783 -37.5647.812 1.0039.54 N

ATOM1184 N ASN A164 10.103 -39.4675.368 1.0030.15 N

ATOM1185 CA ASN A164 9.990 -40.7636.033 1.0029.07 C

ATOM1186 C ASN A164 9.816 -41.9055.039 1.0027.90 C

ATOM1187 O ASN A164 10.274 -43.0195.284 1.0027.31 0 ATOM1188 CB ASN A164 8.821 -40.7687.021 1.0029.09 C

ATOM1189 CG ASN A164 9.085 -39.9108.244 1.0030.98 C

ATOM1190 OD1 ASN A164 10.194 -39.9038.790 1.0031.70 0 ATOM1191 ND2 ASN A164 8.061 -39.1998.696 1.0029.16 N

ATOM1192 N PHE A165 9.161 -41.6283.916 1.0026.30 N

ATOM1193 CA PHE A165 8.935 -42.6542.895 I.0027.59 C

ATOM1194 C PHE A165 9.228 -42.1181.508 1.0028.53 C

ATOM1195 O PHE A165 8.305 -41.8700.725 1.0029.00 0 ATOM1196 CB PHE A165 7.480 -43.1502.931 1.0026.10 C

ATGM1197 CG PHE A165 7.022 -43.5944.288 1.0027.45 C

ATOM1198 CD1 PHE A165 6.488 -42.6795.190 1.0026.53 C

ATOM1199 CD2 PHE A165 7.150 -44.9234.677 1.0027.06 C

ATOM1200 CE1 PHE A165 6.086 -43.0866.461 1.0028.82 C

ATOM1201 CE2 PHE A165 E~.752 -45.3425.951 1.0025.79 C

ATGM1202 CZ PHE A165 6.219 -44.4266.843 1.0025.08 C

ATOM1203 N PRO A166 10.518 -41.9261.176 1.0029.66 N

ATOM1204 CA PRO A166 10.865 -41.410-0.152 1.0029.60 C

ATOM1205 C PRO A166 10.384 -42.315-1.290 1.0030.21 C

ATC>M1206 0 PRO A166 10.193 -91.854-2.412 1.0030.45 0 ATOM1207 CB PRO A166 12.390 -41.299-0.091 1.0031.87 C

ATOM1208 CG PRO A166 12.772 -92.4010.865 1.0031.46 C

ATOM1209 CD PRO A166 11.731 -42.2391.953 1.0029.79 C

ATOM1210 N GLN A167 10.187 -93.598-0.999 1.0030.75 N

ATOM1211 CA GLN A167 9.723 -94.541-2.014 1.0032.40 C

ATOM1212 C GLN A167 8.187 -44.604-2.150 1.0031.19 C

ATOM1213 0 GLN A167 7.677 -45.218-3.085 1.0030.89 0 ATOM1214 CB GLN A167 10.265 -45.950-1.721 1.0034.63 C

ATOM 1215 CG GLNA 167 9.522 -46.697-0.6021.00 39.76 C

ATC)M1216 CD GLNA 167 9.906 -96.2350.800 1.00 41.44 C

ATOM 1217 OEl GLNA 167 10.213 -95.0631.026 1.00 41.18 O

ATOM 1218 NE2 GLNA 167 9.872 -97.1611.753 1.00 43.60 N

ATOM 1219 N ALAA 168 7.446 -93.991-1.2261.00 30.20 N

ATOM 1220 CA ALAA 168 5.977 -44.010-1.3181.00 28.31 C

ATOM 1221 C ALAA 168 5.533 -43.300-2.5991.00 27.38 C

ATOM 1222 0 ALAA 168 6.042 -92.228-2.9191.00 27.21 0 ATOM 1223 CB ALAA 168 5.369 -43.321-0.1121.00 28.83 C

ATOM 1224 N ILEA 169 4.585 -43.877-3.3381.00 25.59 N

ATOM 1225 CA ILEA 169 4.146 -43.225-4.5751.00 25.91 C

ATOM 1226 C ILEA 169 2.775 -42.549-4.5091.00 25.53 C

ATOM 1227 0 ILEA 169 2.457 -41.709-5.3541.00 27.47 0 ATOM 1228 CB ILEA 169 4.146 -44.199-5.7771.00 25.95 C

ATOM 1229 CG1 ILEA 169 3.109 -45.298-5.5671.00 27.04 C

ATOM 1230 CG2 ILEA 169 5.536 -44.813-5.9551.00 27.98 C

ATOM 1231 CD1 ILEA 169 :?.970 -46.224-6.7621.00 28.61 C

ATOM 1232 N ALAA 170 1.966 -42.902-3.5161.00 24.95 N

ATOM 1233 CA ALAA 170 0.637 -42.301-3.3721.00 24.60 C

ATOM 1234 C ALAA 170 ().231 -42.221-1.9081.00 24.79 C

ATOM 1235 0 ALAA 170 0.738 -42.967-1.0721.00 22.08 0 ATOM 1236 CB ALAA 170 -0.407 -43.115-4.1551.00 25.48 C

ATOM 1237 N VALA 171 -0.709 -41.330-1.6071.00 23.90 N

ATOM 1238 CA VALA 171 -1.168 -41.154-0.2401.00 23.66 C

ATOM 1239 C VALA 171 -2.670 -40.883-0.1791.00 25.47 C

ATC)M1240 0 VALA 171 -3.239 -40.241-1.0641.00 25.05 0 ATOM 1241 CB VALA 171 -0.417 -39.9660.438 1.00 24.52 C

ATOM 1242 CG1 VALA 171 -0.575 -38.703-0.4081.00 24.19 C

ATOM 1243 CG2 VALA 171 -0.961 -;39.7221.844 1.00 22.96 C

ATOM 1244 N GLUA 172 -3.311 -41.4090.856 1.00 26.69 N

ATOM 1245 CA GLUA 172 -4.729 -41.1741.069 1.00 26.75 C

ATOM 1246 C GLUA 172 -5.102 -41.5052.511 1.00 25.68 C

ATOM 1247 0 GLUA 172 -4.226 -41.5143.381 1.00 25.15 O

ATOM 1248 CB GLUA 172 -5.593 -41.9080.023 1.00 27.03 C

ATOM 1249 CG GLUA 172 -5.218 -43.338-0.3071.00 28.09 C

ATOM 1250 CD GLUA 172 -5.600 -44.3150.786 1.00 29.36 C

ATOM 1251 OE1 GLUA 172 -4.758 -44.5781.668 1.00 31.82 O

ATOM 1252 OE2 GLUA 172 -6.793 -44.8170.757 1.00 29.54 0 ATOM 1253 N META 173 -6.367 -4:1.7892.793 1.0024.26 N

ATOM 1254 CA META 173 -6.752 -41.9934.185 1.0023.89 C

ATOM 1255 C META 173 -7.304 -4:3.3374.640 1.0024.63 C

ATOM 1256 0 META 173 -7.603 -93.5075.821 1.0024.56 0 ATOM 1257 CB META 173 -7.749 -40.8874.575 1.0024.26 C

ATOM 1258 CG META 173 -7.257 -39.4624.269 1.0021.33 C

ATOM 1259 SD META 173 -8.511 -38.1734.587 1.0021.12 S

ATOM 1260 CE META 173 -8.828 -38.4096.249 1.0023.30 C

ATOM 1261 N GLUA 174 -7.425 -44.3093.746 1.0029.34 N

ATOM 1262 CA GLUA 174 -8.001 -45.5724.182 1.0024.45 C

ATOM 1263 C GLUA 174 -7.273 -46.8423.804 1.0023.90 C

ATOM 1264 O GLUA 174 -7.480 -47.8734.440 1.0023.93 0 ATOM 1265 CB GLUA 174 -9.453 -45.6783.683 1.0024.55 C

ATOM 1266 CG GLUA 174 -10.409 -44.6464.289 1.0023.35 C

ATOM 1267 CD GLUA 174 -10.476 -43.3483.512 1.0024.40 C

ATOM 1268 OE1 GLUA 174 -10.779 -42.3054.127 1.0024.96 0 ATOM 1269 OE2 GLUA 174 -10.253 -43.3592.283 1.0027.30 0 ATOM 1270 N ALAA 175 -6.417 -46.7722.793 1.0022.79 N

ATOM 1271 CA ALAA 175 -5.723 -47.9672.301 1.0024.40 C

ATOM 1272 C ALAA 175 -5.036 -48.8833.311 1.0025.54 C

ATOM 1273 0 ALAA 175 -5.275 -50.1013.315 1.0026.29 0 ATOM 1274 CB ALAA 175 -9.728 -47.5721.214 1.0023.78 C

ATOM 1275 N THRA 176 -9.183 -48.3154.160 1.0024.28 N

ATOM 1276 CA THRA 176 -3.445 -49.1215.123 1.0023.67 C

ATOM 1277 C THRA 176 -4.287 -49.7256.240 1.0024.21 C

ATOM 1278 0 THRA 176 -3.934 -50.7696.791 1.0023.78 O

ATOM 1279 CB THRA 176 -2.283 -48.3095.720 1.0024.49 C

ATOM 1280 OG1 THRA 176 -1.567 -47.6814.653 1.0021.72 0 ATOM 1281 CG2 THRA 176 -1.323 -49.2186.482 1.0022.98 C

ATOM 1282 N ALAA 177 -5.399 -49.0766.577 1.0023.18 N

ATOM 1283 CA ALAA 177 -6.291 -49.5887.613 1.0022.59 C

ATOM 1284 C ALAA 177 -6.977 -50.8527.084 1.0021.73 C

ATOM 1285 0 ALAA 177 -7.152 -51.8377.808 1.0021.35 0 ATOM 1286 CB ALAA 177 -7.334 -48.5337.967 1.0021.12 C

ATOM 1287 N ILEA 178 -7.365 -50.8185.816 1.0021.10 N

ATOM 1288 CA ILEA 178 -8.018 -51.9605.191 1.0023.31 C

ATOM 1289 C ILEA 178 -7.025 -53.1035.003 1.0023.75 C

ATOM 1290 0 ILEA 178 -7.360 -54.2735.214 1.0025.06 0 ATOM1291 CB ILE A178 -8.663 -51.5413.848 1.0023.96 C

ATOM1292 CG1ILE A178 -9.870 -50.6384.151 1.0023.84 C

ATCM1293 CG2ILE A178 -9.074 -52.7633.042 1.0024.90 C

ATOM1294 CD1ILE A178 -10.583 -50.1132.939 1.0026.15 C

ATOM1295 N ALA A179 -5.795 -52.7634.636 1.0024.80 N

ATOM1296 CA ALA A179 -4.742 -53.7624.452 1.0025.81 C

ATOM1297 C ALA A179 -4.444 -54.4115.799 1.0026.87 C

ATOM1298 0 ALA A179 -4.229 -55.6255.891 1.0028.41 O

ATOM1299 CB ALA A179 -3.481 -53.0953.907 1.0025.92 C

ATOM1300 N HIS A180 -9.436 -53.5876.844 1.0026.19 N

ATOM1301 CA HIS A180 -9.166 -54.0408.203 1.0025.72 C

ATOM1302 C HIS A180 -5.240 -55.0318.669 1.0026.74 C

ATOM1303 0 HIS A180 -9.914 -56.0879.224 1.0026.40 0 ATOM1304 CB HIS A180 -9.092 -52.8129.122 1.0029.85 C

ATOM1305 CG HIS A180 -3.716 -53.11010.541 1.0024.26 C

ATOM1306 ND1HIS A180 -3.418 -52.11111.447 1.0024.17 N

ATOM1307 CD2HIS A180 -3.622 -54.27611.224 1.0023.34 C

ATOM1308 CE1HIS A180 -3.161 -52.64912.627 1.0025.63 C

ATOM1309 NE2HIS A180 -3.278 -53.96012.519 1.0027.40 N

ATOM1310 N VAL A181 -6.513 -54.7088.442 1.0026.47 N

ATOM1311 CA VAL A181 -7.593 -55.6118.848 1.0027.34 C

ATOM1312 C VAL A181 -7.516 -56.9058.035 1.0026.42 C

ATOM1313 0 VAL A181 -7.713 -57.9888.575 1.0027.13 0 ATOM1314 CB VAL A181 -9.002 -54.9638.657 1.0027.53 C

ATOM1315 CG1VAL A181 -10.096 -56.0028.890 1.0028.43 C

ATOM1316 CG2VAL A181 -9.194 -53.8259.658 1.0027.79 C

ATOM1317 N CYS A182 -7.230 -56.7856.741 1.0026.95 N

ATOM1318 CA CYS A182 -7.119 -57.9575.870 1.0026.78 C

ATC>M1319 C CYS A182 -5.984 -58.8286.380 1.0028.02 C

ATC)M1320 0 CYS A182 -6.102 -60.0566.423 1.0027.74 0 ATOM1321 CB CYS A182 -6.835 -57.5434.420 1.0024.28 C

ATOM1322 SG CYS A182 -8.258 -56.8573.536 1.0027.27 S

ATC)M1323 N HIS A183 -4.887 -58.1806.764 1.0027.72 N

ATOM1324 CA HIS A183 -3.720 -58.8757.298 1.0029.52 C

ATC)M1325 C HIS A183 -4.113 -59.6748.544 1.0029.64 C

ATOM1326 0 HIS A183 -3.798 -60.8628.652 1.0028.53 O

ATOM1327 CB HIS A183 -2.622 -57.8677.669 1.0031.38 C

ATOM1328 CG HIS A183 -1.460 -58.4808.384 1.0032.70 C

AT01K1329 ND1 HISA 183 -0.904 -59.0737.722 1.0033.97 N

ATOM 1330 CD2 HISA 183 -1.221 -58.6569.706 1.0032.59 C

ATOM 1331 CE1 HISA 183 0.432 -59.5898.605 1.0032.18 C

ATOM 1332 NE2 HISA 183 -0.041 -59.3519.816 1.0032.09 N

ATOM 1333 N ASNA 184 -4.796 -59.0219.482 1.0029.04 N

ATOM 1334 CA ASNA 184 -5.221 -59.68810.707 1.0029.85 C

ATOM 1335 C ASNA 184 -6.203 -60.81910.448 1.0029.23 C

ATOM 1336 0 ASNA 184 -6.299 -61.73611.254 1.0030.25 0 ATOM 1337 CB ASNA 184 -5.859 -58.70311.692 1.0031.80 C

ATOM 1338 CG ASNA 184 -4.831 -57.87212.446 1.0033.17 C

ATOM 1339 ODl ASNA 184 -5.118 -57.34613.517 1.0035.11 0 ATOM 1340 ND2 ASNA 184 -3.636 -57.73911.882 1.0032.18 N

ATOM 1341 N PHEA 185 -6.950 -60.7449.349 1.0029.01 N

ATOM 1342 CA PHEA 185 -7.907 -61.8009.005 1.0029.35 C

ATOM 1343 C PHEA 185 -7.258 -62.8038.053 1.0030.55 C

ATOM 1344 0 PHEA 185 -7.900 -63.7587.610 1.0028.77 0 ATOM 1345 CB PHEA 185 -9.153 -61.2218.325 1.0029.54 C

ATOM 1346 CG PHEA 185 -10.260 -60.8489.277 1.0029.99 C

ATOM 1347 CDl PHEA 185 -10.296 -59.5879.869 1.0030.62 C

ATOM 1348 CD2 PHEA 185 -11.283 -61.7579.564 1.0029.05 C

ATOM 1349 CEl PHEA 185 -11.339 -59.23110.729 1.0030.52 C

ATOM 1350 CE2 PHEA 185 -12.327 -61.41310.421 1.0028.75 C

ATOM 1351 CZ PHEA 185 -12.358 -60.14911.004 1.0030.33 C

ATOM 1352 N ASNA 186 -5.992 -62.5567.726 1.0030.99 N

ATOM 1353 CA ASNA 186 -5.216 -63.4066.830 1.0032.52 C

ATOM 1354 C ASNA 186 -5.916 -63.5845.485 1.0032.41 C

ATOM 1355 0 ASNA 186 -5.949 -64.6794.923 1.0032.54 0 ATOM 1356 CB ASNA 186 -4.953 -64.7667.495 1.0036.85 C

ATOM 1357 CG ASNA 186 -3.907 -65.5896.753 1.0041.27 C

ATOM 1358 OD1 ASNA 186 -2.842 -65.0816.390 1.0043.73 0 ATOM 1359 ND2 ASNA 186 -9.200 -66.8696.536 1.0093.77 N

ATOM 1360 N VALA 187 -6.475 -62.4894.976 1.0030.80 N

ATOM 1361 CA VALA 187 -7.171 -62.4823.696 1.0029.22 C

ATOM 1362 C VALA 187 -6.333 -61.6712.705 1.0029.42 C

ATOM 1363 0 VALA 187 -~>.962 -60.5342.987 1.0028.13 O

ATOM 1364 CB VALA 187 -8.582 -61.8383.837 1.0029.24 C

ATC>M1365 CG1 VALA 187 -9.222 -61.6282.462 1.0027.71 C

ATOM 1366 CG2 VALA 187 -9.467 -62.7379.688 1.0029.26 C

ATOM 1367 N PROA 188 -6.003 -62.2581.541 1.00 29.21 N

ATOM 1368 CA PROA 188 -5.201 -61.5580.529 1.00 28.87 C

ATOM 1369 C PROA 188 -5.933 -60.3030.049 1.00 27.34 C

ATOM 1370 0 PROA 188 -'1.163 -60.297-0.0471.00 25.56 0 ATOM 1371 CB PROA 188 -5.070 -62.590-0.5911.00 30.14 C

ATOM 1372 CG PROA 188 -5.213 -63.9050.127 1.00 31.40 C

ATOM 1373 CD PROA 188 -6.322 -63.6251.103 1.00 29.66 C

ATOM 1374 N PHEA 189 -5.189 -~i9.245-0.2521.00 25.24 N

ATOM 1375 CA PHEA 189 -5.821 -58.016-0.7171.00 25.95 C

ATOM 1376 C PHEA 189 -4.942 -57.324-1.7341.00 25.41 C

ATOM 1377 0 PHEA 189 -3.776 -_'17.662-1.9091.00 26.89 0 ATOM 1378 CB PHEA 189 -6.038 -57.0250.444 1.00 24.35 C

ATOM 1379 CG PHEA 189 -4.763 -'.16.3340.886 1.00 26.07 C

ATOM 1380 CD1 PHEA 189 -3.922 -56.9211.821 1.00 27.46 C

ATOM 1381 CD2 PHEA 189 -4.356 -_'15.1480.282 1.00 26.63 C

ATOM 1382 CE1 PHEA 189 -2.691 -56.3462.146 1.00 27.24 C

ATOM 1383 CE2 PHEA 189 -3,129 -.'14.5640.596 1.00 27.42 C

ATOM 1384 CZ PHEA 189 -2.293 -55.1681.531 1.00 27.12 C

ATOM 1385 N VALA 190 -5.530 -'16.352-2.4141.00 24.28 N

ATOM 1386 CA VALA 190 -4.800 -.'15.515-3.3371.00 22.61 C

ATOM 1387 C VALA 190 -5.496 -54.165-3.2201.00 24.46 C

ATOM 1388 0 VALA 190 -6.730 -.'14.083-3.1641.00 23.65 0 ATOM 1389 CB VALA 190 -4.843 -56.013-9.8011.00 23.23 C

ATOM 1390 CG1 VALA 190 -6.235 -55.868-5.3831.00 24.15 C

ATOM 1391 CG2 VALA 190 -:3.832 -'.15.219-5.6271.00 24.16 C

ATOM 1392 N VALA 191 -4.699 -53.110-3.1231.00 24.53 N

ATt)M1393 CA VALA 191 -5.240 -51.767-3.0381.00 24.12 C

ATOM 1394 C VALA 191 -4.964 -51.131-4.3871.00 23.67 C

ATt)M1395 0 VALA 191 -3.857 -51.243-4.9091.00 25.32 0 ATOM 1396 CB VALA 191 -4.541 -50.961-1.9301.00 24.04 C

ATOM 1397 CG1 VALA 191 -4.825 -49.477-2.1081.00 22.49 C

ATOM 1398 CG2 VALA 191 -5.016 -51.450-0.5621.00 22.25 C

ATOM 1399 N VALA 192 -5.979 -50.496-4.9641.00 22.85 N

ATOM 1400 CA VALA 192 -5.849 -49.834-6.2561.00 23.70 C

ATOM 1401 C VALA 192 -6.430 -48.442-6.0781.00 23.65 C

ATOM 1402 0 VALA 192 -7.492 -48.292-5.4751.00 23.69 0 ATOM 1403 CB VALA 192 -6.649 -50.574-7.3621.00 25.96 C

ATOM 1404 CGl VALA 192 -6.484 -49.860-8.6921.00 25.72 C

ATOM 1405 CG2 VALA 192 -6.168 -52.020-7.480 1.0026.52 C

ATOM 1406 N ARGA 193 -5.732 -4'7.434-6.596 1.0023.35 N

ATOM 1407 CA ARGA 193 -6.177 -46.054-6.484 1.0024.09 C

ATOM 1408 C ARGA 193 -5.937 -45.236-7.758 1.0025.66 C

ATOM 1409 O ARGA 193 -4.841 -45.243-8.333 1.0026.00 0 ATOM 1410 CB ARGA 193 -5.451 -45.368-5.317 1.0023.40 C

ATOM 1411 CG ARGA 193 -5.734 -45.962-3.950 1.0023.40 C

ATOM 1412 CD ARGA 193 -7.085 -45.501-3.434 1.0024.09 C

ATOM 1413 NE ARGA 193 -7.306 -45.897-2.048 1.0023.76 N
, ATOM 1414 CZ ARGA 193 -7.662 -4'7.118-1.670 1.0025.39 C

ATOM 1415 NH1 ARGA 193 -7.841 -48.066-2.581 1.0025.46 N

ATOM 1416 NH2 ARGA 193 -7.828 -47.393-0.382 1.0025.60 N

ATOM 1417 N ALAA 194 -6.967 -44.523-8.195 1.0025.34 N

ATOM 1418 CA ALAA 194 -6.843 -4:3.669-9.358 1.0024.92 C

ATOM 1419 C ALAA 194 -6.248 -42.377-8.800 1.0025.39 C

ATOM 1420 0 ALAA 194 -6.699 -41.880-7.767 1.0023.64 0 ATOM 1421 CB ALAA 194 -8.211 -4.3.414-9.965 1.0025.86 C

ATOM 1422 N ILEA 195 -5.233 -41.841-9.466 1.0025.55 N

ATOM 1423 CA ILEA 195 -4.596 -40.620-8.983 1.0026.41 C

ATOM 1424 C ILEA 195 -5.397 -39.380-9.383 1.0027.03 C

ATOM 1425 0 ILEA 195 -5.516 -39.049-10.5611.0027.59 0 ATOM 1426 CB ILEA 195 -3.153 -40.530-9,505 1.0025.76 C

ATOM 1427 CG1 ILEA 195 -2.347 -41.714-8,960 1.0025.07 C

ATOM 1428 CG2 ILEA 195 -2.497 -39.223-9.056 1.0025.36 C

ATOM 1429 CD1 ILEA 195 -2.284 -41.770-7,423 1.0024.49 C

ATOM 1430 N SERA 196 -5.951 -38.709-8.381 1.0028.06 N

ATOM 1431 CA SERA 196 -6.770 -37.525-8.598 1.0029.83 C

ATOM 1432 C SERA 196 -5.955 -36.249-8.743 1.0031.78 C

ATOM 1433 0 SERA 196 -6.393 -35.290-9.379 1.0032.56 0 ATOM 1434 CB SERA 196 -7.754 -37.373-7.441 1.0028.11 C

ATOM 1435 OG SERA 196 -7.072 -37.367-6.201 1.002$.08 0 ATOM 1436 N ASPA 197 -4.774 -36.237-8.142 1.0033.95 N

ATOM 1437 CA ASPA 197 -3.901 -35.075-8.200 1.0036.14 C

ATOM 1438 C ASPA 197 -2.483 -35.488-7.862 1.0036.80 C

ATOM 1439 O ASPA 197 -2.268 -36.502-7.193 1.0036.97 0 ATOM 1440 CB ASPA 197 -4.364 -34.025-7.199 1.0038.72 C

ATOM 1441 CG ASPA 197 -4.583 -34.606-5.825 1.0041.89 C

ATOM 1442 OD1 ASPA 197 -5.693 -35.119-5.562 1.0044.62 0 ATOIK1443 OD2 ASPA 197 -3.639 -34.571-5.0091.00 45.77 0 ATOM 1444 N VALA 198 -1.519 -34.700-8.3241.00 36.42 N

ATOlK1445 CA VALA 198 -0.120 -34.974-8.0591.00 37.83 C

ATO1K1446 C VALA 198 0.452 -33.831-7.2221.00 39.04 C

ATO1M1447 0 VALA 198 0.255 -32.655-7.5321.00 37.18 0 ATOIM1448 CB VALA 198 0.666 -3'.1.128-9.3701.00 38.54 C

ATO1M1449 CG1 VALA 198 2.097 -35.529-9.0751.00 40.20 C

ATOIM1450 CG2 VALA 198 -0.003 -36.179-10.2421.00 39.58 C

ATOIM1451 N ALAA 199 1.151 -34.205-6.1551.00 40.82 N

ATOM 1452 CA ALAA 199 1.749 -3:3.280-5.1961.00 93.23 C

ATOM 1453 C ALAA 199 2.249 -3:1.935-5.7171.00 44.52 C

ATOM 1454 0 ALAA 199 1.819 -30.888-5.2261.00 44.81 0 ATOM 1455 CB ALAA 199 2.869 -33.987-4.4421.00 42.74 C

ATOM 1456 N ASPA 200 3.149 -3:1.948-6.6981.00 45.65 N

ATOM 1457 CA ASPA 200 3.692 -3().695-7.2141.00 47.74 C

ATOM 1458 C ASPA 200 3.351 -30.346-8.6581.00 48.66 C

ATOM 1459 0 ASPA 200 4.210 -29.877-9.4101.00 48.65 0 ATOM 1460 CB ASPA 200 5.219 -30.663-7.0361.00 47.39 C

ATOM 1461 CG ASPA 200 5.923 -3:1.782-7.7811.00 47.59 C

ATOM 1462 OD1 ASPA 200 7.167 -3:1.734-7.8821.00 44.05 0 ATOM 1463 OD2 ASPA 200 5.239 -32.711-8.2591.00 48.33 0 ATOM 1464 N GLNA 201 2.097 -30.560-9.0411.00 49.78 N

ATOM 1465 CA GLNA 201 1.647 -30.238-10.3931.00 51.03 C

ATOM 1466 C GLNA 201 0.257 -29.618-10.3301.00 51.52 C

ATOM 1467 0 GLNA 201 -0.370 -2'x.712-9.2541.00 51.75 0 ATOM 1468 CB GLNA 201 1.625 -31.493-11.2581.00 51.46 C

ATOM 1469 N SERA 206 -10.263 -30.961-14.2781.00 51.87 N

ATOM 1470 CA SERA 206 -11.650 -30.702-13.7891.00 52.25 C

ATOM 1471 C SERA 206 -12.169 -31.827-12.8951.00 51.76 C

ATOM 1472 0 SERA 206 -:11.940-33.006-13,1641.00 51.28 0 ATOM 1473 CB SERA 206 -12.605 -30.509-14.9661.00 52.74 C

ATOM 1474 OG SERA 206 -13.956 -30.679-14.5691.00 52.06 0 ATOM 1475 N PHEA 207 -12.876 -31.439-11.8381.00 51.26 N

ATOM 1476 CA PHEA 207 -13.446 -32.379-10.8781.00 50.59 C

ATOM 1477 C PHEA 207 -14.180 -33.527-11.5601.00 49.68 C

ATOM 1478 0 PHEA 207 -13.788 -34.686-11.4431.00 50.43 0 ATOM 1479 CB PHEA 207 -14.921 -31.649-9.9561.00 50.27 C

ATOM 1480 CG PHEA 207 -15.012 -32.520-8.8911.00 49.41 C

ATOM 1481 CD1 PHEA 207 -14.320 -32.760-7.7081.00 49.27 C

ATOIM1482 CD2 PHEA 207 -16.261 -3:3.109-9.0731.00 49.34 C

ATOIM1483 CE1 PHEA 207 -1.4.863-33.574-6.7151.00 49.38 C

ATOIM1484 CE2 PHEA 207 -16.816 -3:3.927-8.0891.00 49.91 C

ATO1M1485 CZ PHEA 207 -16.116 -34.160-6.9071.00 50.23 C

ATO1M1486 N ASPA 208 -15.255 -33.189-12.2631.00 48.76 N

ATO1M1487 CA ASPA 208 -16.065 -34.168-12.9701.00 48.52 C

ATOIM1488 C ASPA 208 -15.228 -34.937-13.9731.00 47.27 C

ATO1M1489 O ASPA 208 -15.305 -36.161-14.0481.00 96.13 0 ATO1H1490 CB ASPA 208 -17.209 -33.471-13.7101.00 50.85 C

ATOM 1491 CG ASPA 208 -18.:155-3:?.754-12.7751.00 52.92 C

ATO1H1492 OD1 ASPA 208 -17.671 -31.969-11.9301.00 54.48 0 ATOM 1493 OD2 ASPA 208 -19.380 -32.972-12.8911.00 54.07 0 ATOM 1494 N GLUA 209 -14.432 -34.213-14.7501.00 46.00 N

ATOIK1495 CA GLUA 209 -13.595 -34.850-15.7521.00 45.96 C

ATOM 1496 C GLUA 209 -:12.748-35.958-15.1371.00 44.46 C

ATOM 1497 0 GLUA 209 -12.414 -36.931-15.8091.00 45.95 0 ATOIM1498 CB GLUA 209 -12.714 -33.813-16.4471.00 47.82 C

ATO1M1499 CG GLUA 209 -13.529 -32.760-17.1851.00 51.93 C

ATO1N1500 CD GLUA 209 -12.678 -31.841-18.0351.00 54.84 C

ATOM 1501 OE1 GLUA 209 -11.690 -31.286-17.5081.00 56.91 0 ATO1M1502 OE2 GLUA 209 -13.002 -3:L.667-19.2301.00 56.50 0 ATOM 1503 N PHEA 210 -:L2.405-35.823-13.8601.00 40.50 N

ATOM 1504 CA PHEA 210 -11.626 -36.865-13.2141.00 36.53 C

ATOM 1505 C PHEA 210 -12.529 -37.891-12.5461.00 35.90 C

ATO1M1506 0 PHEA 210 -12.471 -39.076-12.8691.00 35.30 0 ATO1M1507 CB PHEA 210 -1Ø687-36.311-12.1451.00 32.94 C

ATO1M1508 CG PHEA 210 -10.156 -37.377-11.2281.00 32.09 C

ATOIM1509 CD1 PHEA 210 -9.134 -38.226-11.6481.00 29.89 C

ATOiM1510 CD2 PHEA 210 -1Ø'752-3'7.604-9.9861.00 30.37 C

ATOM 1511 CE1 PHEA 210 -8.714 -3!3.290-10.8501.00 29.56 C

ATOM 1512 CE2 PHEA 210 -10.344 -38.667-9.1741.00 31.37 C

ATOM 1513 CZ PHEA 210 -9.317 -3!x.516-9.6121.00 30.45 C

ATOM 1514 N LEUA 211 -13.361 -37.430-11.6151.00 34.84 N

ATOM 1515 CA LEUA 211 -14.233 -38.323-10.8711.00 36.06 C

ATOM 1516 C LEUA 211 -15.244 -39.091-11.7071.00 36.07 C

ATOM 1517 0 LEUA 211 -15.480 -40.273-11.4621.00 37.05 O

ATOM 1518 CB LEUA 211 -14.961 -3'7.564-9.7601.00 36.68 C

ATOM 1519 CG LEUA 211 -15.498 -38.501-8.6701.00 36.90 C

ATOM 1520 CD1 LEUA 211 -14.326 -39.273-8.0451.00 34.78 C

ATOM 1521 CD2 LEUA 211 -16.239 -37.710-7.6071.00 35.74 C

ATOM 1522 N ALAA 212 -15.848 -38.429-12.6861.00 37.30 N

ATOM 1523 CA ALAA 212 -16.825 -39.090-13.5391.00 37.02 C

ATOM 1524 C ALAA 212 -16.137 -40.233-14.2771.00 36.30 C

ATOM 1525 0 ALAA 212 -16.661 -41.348-14.3501.00 36.08 0 ATOM 1526 CB ALAA 212 -17.415 -38.094-14.5341.00 38.40 C

ATOM 1527 N VALA 213 -14.948 -39.944-14.7951.00 35.09 N

ATOM 1528 CA VALA 213 -14.144 -40.910-15.5381.00 39.25 C

ATOM 1529 C VALA 213 -13.516 -41,996-14.6601.00 33.43 C

ATOM 1530 0 VALA 213 -13.630 -43.180-19.9661.00 33.99 0 ATOM 1531 CB VALA 213 -12.999 -40.196-16.3061.00 36.10 C

ATOM 1532 CG1 VALA 213 -12.181 -42.208-17.1021.00 37.24 C

ATOM 1533 CG2 VALA 213 -13.581 -:39.128-17.2361.00 38.14 C

ATOM 1534 N ALAA 214 -12.853 -41.595-13.5771.00 31.16 N

ATOM 1535 CA ALAA 214 -12.187 -42.548-12.6881.00 28.81 C

ATOM 1536 C ALAA 214 -13.121 -43.588-12.0871.00 27.67 C

ATOM 1537 0 ALAA 214 -12.793 -44.775-12.0411.00 25.76 O

ATOM 1538 CB ALAA 214 -11.449 -41.804-11.5701.00 29.67 C

ATOM 1539 N ALAA 215 -14.281 -43.143-11.6301.00 25.90 N

ATOM 1540 CA ALAA 215 -15.255 -44.037-11.0221.00 27.36 C

ATOM 1541 C ALAA 215 -15.806 -45.060-12.0171.00 28.93 C

ATOM 1592 0 ALAA 215 -15.982 -46.234-11.6791.00 29.96 0 ATOM 1543 CB ALAA 215 -1.6.390-43.223-10.4211.00 27.82 C

ATOM 1544 N LYSA 216 -16.078 -44.619-13.2401.00 28.46 N

ATOM 1545 CA LYSA 216 -16.603 -45.512-14.2661.00 29.77 C

ATOM 1546 C LYSA 216 -15.553 -46,545-14.6371.00 29.74 C

ATOM 1547 O LYSA 216 -15.825 -47.746-14.6461.00 29.94 0 ATOM 1548 CB LYSA 216 -16.998 -44.716-15.5151.00 32.54 C

ATOM 1549 CG LYSA 216 -17.474 -45.570-16.6921.00 33.97 C

A'POM1550 CD LYSA 216 -18.807 -46.251-16.3991.00 37.51 C

ATOM 1551 CE LYSA 216 -:19.222-47.178-17.5371.00 40.61 C

ATOM 1552 NZ LYSA 216 '20.522 -47.863-17.2571.00 43.19 N

ATOM 1553 N GLNA 217 -14.349 --46.074-14.9411.00 28.78 N

ATOM 1554 CA GLNA 217 -13.263 ~-46.963-15.3281.00 28.61 C

ATOM 1555 C GLNA 217 -12.840 -47.905-14.1991.00 28.43 C

ATOM 1556 O GLNA 217 -12.470 -49.054-14.4431.00 27.93 O

ATOM 1557 CB GLNA 217 -12.071 -46.138-15.8291.00 31.54 C

ATOM 1558 CG GLNA 217 -12.367 -45.386-17.1381.00 35.01 C

ATOM 1559 CD GLNA 217 -13.055 -46.276-18.1871.00 40.12 C

ATOM 1560 OE1 GLNA 217 -12.503 -47.295-18.6221.00 38.58 0 ATOM 1561 NE2 GLNA 217 -14.268 -45.890-18.5881.00 39.77 N

ATGM 1562 N SERA 218 -12.893 -47.423-12.9651.00 26.87 N

ATOM 1563 CA SERA 218 -12.540 -48.262-11.8321.00 26.89 C

ATOM 1564 C SERA 218 -13.568 -49.385-11.7201.00 26.14 C

ATOM 1565 0 SERA 218 -13.208 -50.531-11.4591.00 26.91 0 ATOM 1566 CB SERA 218 -12.525 -47.448-10.5371.00 25.78 C

ATOM 1567 OG SERA 218 -12.069 -98.242-9.453 1.00 27.49 O

ATOM 1568 N SERA 219 -14.842 -49.063-11.9271.00 26.03 N

ATOM 1569 CA SERA 219 -15.893 -50.080-11.8411.00 27.24 C

ATOM 1570 C SERA 219 -15.707 -51.141-12.9291.00 27.53 C

ATOM 1571 0 SERA 219 -15.903 -52.333-12.6791.00 27.54 0 ATOM 1572 CB SERA 219 -17.286 -49.438-11.9521.00 26.55 C

ATOM 1573 OG SERA 219 -17.568 -48.997-13.2681.00 26.94 0 ATOM 1574 N LEUA 220 -15,323 -50.714-14.1321.00 26.66 N

ATOM 1575 CA LEUA 220 -15.086 -51.652-15.2291.00 26.94 C

ATOM 1576 C LEUA 220 -13.864 -52.489-14.8851.00 26.84 C

ATOM 1577 0 LEUA 220 -13.811 -53.683-15.1871.00 27.58 0 ATOM 1578 CB LEUA 220 -14.842 -50.907-16.5461.00 26.55 C

ATOM 1579 CG LEUA 220 -16.047 -50.185-17.1481.00 28.43 C

ATOM 1580 CD1 LEUA 220 -15.603 -49.419-18.3791,00 29.06 C

ATOM 1581 CD2 LEUA 220 -17.144 -51.204-17.5051.00 28.88 C

ATOM 1582 N META 221 -12.873 -51.850-14.2631.00 26.09 N

ATOM 1583 CA META 221 -11.654 -52.543-13.8491.00 26.51 C

ATOM 1584 C META 221 -11.995 -53.631-12.8281.00 25.38 C

ATOM 1585 O META 221 -11.476 -54.743-12.9081.00 26.63 0 ATOM 1586 CB META 221 -10.661 -51.562-13.2171.00 26.76 C

ATOM 1587 CG META 221 -9.389 -52.240-12.6931.00 28.97 C

ATOM 1588 SD META 221 -8.445 -51.245-11.5241.00 29.44 S

ATOM 1589 CE META 221 -9.471 -51.476-10.0401.00 28.74 C

ATOM 1590 N VALA 222 -12.855 -53.295-11.8651.00 25.47 N

A'.POM1591 CA VALA 222 -13.276 '54.241-10.8311.00 27.15 C

ATOM 1592 C VALA 222 -14.039 -55.408-11.4591.00 29.63 C

A'POM1593 0 VALA 222 -13.802 -56.571-11.1231.00 29.15 0 ATOM 1594 CB VALA 222 -14.199 -53.575-9.783 1.00 26.95 C

ATOM 1595 CG1 VALA 222 -14.820 -54.640-8.884 1.00 23.39 C

ATOM 1596 CG2 VALA 222 -13,410 -52.576-8.947 1.00 24.63 C

ATOM 1597 N GLUA 223 -14.959 -55.087-12.3631.00 29.36 N

ATOM 1598 CA GLUA 223 -15.747 -56.104-13.0431.00 31.35 C

ATOM 1599 C GLUA 223 -14.814 -5'7.043-13.8081.00 30.81 C

ATOM 1600 0 GLUA 223 -14.972 -58.265-13.7631.00 30.00 0 ATOM 1601 CB GLUA 223 -16.748 -55.425-13.9831.00 32.97 C

ATOM 1602 CG GLUA 223 -17.628 -56.352-14.7901.00 37.40 C

ATOM 1603 CD GLUA 223 -18.878 -55.651-15.2851.00 39.97 C

ATOM 1604 OEI GLUA 223 -18.803 -54.434-15.5801.00 42.16 0 ATOM 1605 OE2 GLUA 223 -19.934 -56.313-15.3821.00 41.93 0 ATC)M1606 N SERA 224 -13.828 -56.475-14.4951.00 30.17 N

ATOM 1607 CA SERA 224 -12.872 -57.286-15.2401.00 31.52 C

ATUM 1608 C SERA 224 -11.978 -58.100-14.3041.00 30.39 C

ATOM 1609 O SERA 224 -11.629 -59.240-14.6001.00 31.67 0 ATOM 1610 CB SERA 224 -11.996 -56.396-16.1311.00 33.99 C

ATOM 1611 OG SERA 224 -10.998 -57.166-16.7851.00 37.30 0 ATOM 1612 N LEUA 225 -11.609 -57.521-13.1701.00 29.85 N

ATOM 1613 CA LEUA 225 -10.745 -58.224-12.2271.00 30.64 C

ATOM 1614 C LEUA 225 -11.491 -59.360-11.5381.00 30.83 C

ATOM 1615 0 LEUA 225 -10.900 -60.397-11.2261.00 31.57 0 ATOM 1616 CB LEUA 225 -10.178 -57.244-11.1891.00 31.12 C

ATOM 1617 CG LEUA 225 -9.207 -57.826-10.1551.00 32.24 C

ATOM 1618 CD1 LEUA 225 -8.072 -58.542-10.8621.00 32.20 C

ATOM 1619 CD2 LEUA 225 -8.671 -56.711-9.259 1.00 32.61 C

ATOM 1620 N VALA 226 -J.2.788-59.169-11.3121.00 30.35 N

ATOM 1621 CA VALA 226 -13.607 -60.188-10.6711.00 32.80 C

ATOM 1622 C VALA 226 -13.693 -61.418-11.5771.00 35.19 C

ATOM 1623 0 VALA 226 -13.485 -62.550-11.1261.00 36.14 0 A'COM1624 CB VALA 226 -15.029 -59.647-10.3641.00 32.01 C

A'POM1625 CG1 VALA 226 -15.948 --60.7?7-9.915 1.00 31.57 C

ATOM 1626 CG2 VALA 226 -19.951 -58.594-9.263 1.00 30.59 C

ATOM 1627 N GLNA 227 -13.982 -61.189-12.8541.00 36.66 N

ATOM 1628 CA GLNA 227 -14.084 -62.276-13.8211.00 39.36 C

ATOM 1629 C GLNA 227 -12.740 -62.987-13.9791.00 40.04 C

ATOM 1630 0 GLNA 227 -12.680 -64.215-14.0401.00 40.46 0 ATOM 1631 CB GLNA 227 -14.549 -61.737-15.1791.00 40.15 C

ATOM 1632 CG GLNA 227 -14.854 -62.825-16.2061.00 44.82 C

ATOM 1633 CD GLNA 227 -15.845 -63.861-15.6891.0047.34 C

ATOM 1634 OE1 GLNA 227 -17.009 -63.549-15.4211.0048.70 O

ATOM 1635 NE2 GLNA 227 -15.381 -65.100-15.5251.0048.08 N

ATOM 1636 N LY5A 228 -11.663 -62.211-14.0311.0040.28 N

ATOM 1637 CA LYSA 228 -10.325 -62.770-14.1861.0041.06 C

ATOM 1638 C LYSA 228 -10.002 -63.721-13.0381.0041.49 C

ATOM 1639 O LYSA 228 -9.608 -64.863-13.2581.0042.88 0 ATOM 1640 CB LYSA 228 -9.287 -61.648-14.2281.0041.71 C

ATOM 1641 CG LYSA 228 -8.171 -61.880-15.2251.0043.24 C

ATC>M1642 CD LYSA 228 -7.122 -60.782-15.1561.0042.72 C

ATOM 1643 CE LYSA 228 -6.256 -60.784-16.4071.0043.75 C

ATOM 1644 NZ LYSA 228 -7.057 -60.443-17.6231.0043.39 N

ATUM 1645 N LEUA 229 -10.171 -63.247-11.8091.0041.47 N

ATOM 1646 CA LEUA 229 -9.895 -64.066-10.6371.0041.35 C

ATOM 1647 C LEUA 229 -10.870 -65.240-10.5611.0043.11 C

ATOM 1648 0 LEUA 229 -10.576 -66.258-9.935 1.0043.53 0 ATOM 1649 CB LEUA 229 -10.002 -63.220-9.371 1.0039.34 C

ATOM 1650 CG LEUA 229 -9.053 -62.022-9.282 1.0038.40 C

ATOM 1651 CD1 LEUA 229 -9.389 -61.186-8.050 1.0037.42 C

ATOM 1652 CD2 LEUA 229 -7.622 -62.511-9.234 1.0036.43 C

ATOM 1653 N ALAA 230 -12.031 -65.093-11.1991.0044.22 N

ATOM 1654 CA ALAA 230 -13.036 -66.156-11.2061.0045.23 C

ATOM 1655 C ALAA 230 -12.634 -67.256-12.1851.0045.93 C

ATOM 1656 0 ALAA 230 -1.2.240-66.917-13.3241.0046.25 0 ATOM 1657 CB ALAA 230 -14.392 -65.592-11.5941.0044.09 C

ATOM 1659 N METB 1 -29.622 -56.93331.030 1.0041.18 N

ATOM 1660 CA METB 1 -28.454 -56.08730.650 1.0040.39 C

ATOM 1661 C METB 1 -'Z7.184-56.89730.404 1.0039.30 C

ATOM 1662 O METB 1 -26.918 -57.87531.101 1.0040,69 0 A'rOM1663 CB METB 1 -28.180 --55.05331.743 1.0041.81 C

A'rOM1664 CG METB 1 -26.887 -54.28331.551 1.0041.99 C

ATOM 1665 SD METB 1 -26.837 -52.78232.533 1.0046.67 S

ATOM 1666 CE METB 1 -27.542 -51.61631.368 1.0041.94 C

ATOM 1667 N LYSB 2 -26.411 -56.98829.400 1.0035.91 N

ATOM 1668 CA LYSB 2 -25.149 -57.14329.072 1.0032.82 C

ATOM 1669 C LYSB 2 -24.091 -56.05528.966 1.0031.65 C

P.TOM1670 0 LYSB 2 -24.273 -55.07328.247 1.0029.80 0 ATOM 1671 CB LYS B 2 -25.231 -57.89327.743 1.0031.31 C

ATOM 1672 CG LYS B 2 -23.917 -58.58327.389 1.0031.90 C

ATOM 1673 CD LYS B 2 -23.960 -59.24226.026 1.0033.22 C

ATOM 1674 CE LYS B 2 -29.972 -60.37725.975 1.0034.12 C

ATOM 1675 NZ LYS B 2 -24.975 -61.03424.633 1.0033.44 N

ATOM 1676 N ILE B 3 -22.984 -56.23829.673 1.0030.50 N

ATOM 1677 CA ILE B 3 -21.922 -55.24529.677 1.0030.33 C

ATOM 1678 C ILE B 3 -20.681 -55.67928.908 1.0029.99 C

ATOM 1679 0 ILE B 3 -20.127 -i6.79929.152 1.0029.21 0 ATOM 1680 CB ILE B 3 -21.534 -54.90031.129 1.0031.17 C

ATOM 1681 CG1 ILE B 3 -22.799 -54.57331.925 1.0032.29 C

ATOM 1682 CG2 ILE B 3 -20.580 -53.70431,158 1.0030.70 C

ATOM 1683 CD1 ILE B 3 -22.552 -54.32333.400 1.0035.93 C

ATOM 1684 N GLY B 4 -20.253 -'.54.83927.969 1.0028.78 N

ATOM 1685 CA GLY B 4 -19.066 -.55.14027.194 1.0027.17 C

ATOM 1686 C GLY B 4 -17.898 -54.46827.886 1.0027.80 C

ATOM 1687 0 GLY B 4 -17.986 -53.29728.264 1.0026.34 0 ATOM 1688 N ILE B 5 -16.817 -55.21828.066 1.0026.14 N

ATOM 1689 CA ILE B 5 -15.617 -54.73428.729 1.0026.83 C

ATOM 1690 C ILE B 5 -14.409 -54.92327.810 1.0027.19 C

ATOM 1691 0 ILE B 5 -19.111 -56.03927.387 1.0026.75 0 ATOM 1692 CB ILE B 5 -15.345 -55.53330.040 1.0026.78 C

ATOM 1693 CG1 ILE B 5 -7.6.584-55.51830.932 1.0026.83 C

A7.'OM1694 CG2 ILE B 5 -14.151 -54.94330.786 1.0025.79 C

ATOM 1695 CD1 ILE B 5 '16.495 -56.49132.106 1.0028.30 C

ATOM 1696 N ILE B 6 -13.716 -53.83027.508 1.0027.05 N

A'POM1697 CA ILE B 6 -12.528 --53.88426.668 1.0026.96 C

A'POM1698 C ILE B 6 -11.405 -53.24527.485 1.0027.50 C

ATOM 1699 0 ILE B 6 -11.459 -52.05627.820 1.0025.90 O

ATOM 1700 CB ILE B 6 -12.750 -53.11225.340 1.0028.57 C

ATOM 1701 CG1 ILE B 6 -13.920 -53.74224.568 1.0028.00 C

ATOM 1702 CG2 ILE B 6 -11.489 -53.15124.488 1.0027.11 C

ATOM 1703 CD1 ILE B 6 -14.249 -53.05323.259 1.0028.94 C

ATOM 1704 N GLY B 7 -10.404 -54.04427.839 1.0027.03 N

ATOM 1705 CA GLY B 7 -9.307 -53.52628.634 1.0027.02 C

ATOM 1706 C GLY B 7 -7.964 -53.65127.954 1.0026.88 C

ATOM 1707 0 GLY B 7 -7.712 -54.62427.254 1.0026.45 0 ATOM 1708 N ALA B 8 -7.090 -52.67228.170 1.0028.04 N

ATOM 1709 CA ALAB 8 -5.765 -52.69027.557 1.0028.23 C

ATOM 1710 C ALAB 8 -4.743 -53.46928.374 1.0030.13 C

ATOM 1711 0 ALAB 8 -3.872 -54.13627.813 1.0030.56 0 ATOM 1712 CB ALAB 8 -5.265 -51.26727.348 1.0027.42 C

ATOM 1713 N METB 9 -4.838 -53.38329.697 1.0031.40 N

ATOM 1714 CA METB 9 -3.876 -54.07530.550 1.0032.60 C

ATOM 1715 C METB 9 -4.135 -55.56830.621 1.0032.93 C

ATOM 1716 0 METB 9 -5.162 -56.01831.123 1.0032.43 0 ATC)M1717 CB METB 9 -3.866 -53.46531.956 1.0031.03 C

ATOM 1718 CG METB 9 -3.397 -52.00231.975 1.0030.24 C

ATOM 1719 SD METB 9 -3.530 -51.18633.568 1.0025.08 S

ATOM 1720 CE METB 9 -5.270 -50.85333.634 1.0029.19 C

ATOM 1721 N GLUB 10 -3.180 -56.32430.100 1.0035.73 N

ATOM 1722 CA GLUB 10 -3.237 -57.77730.078 1.0038.52 C

ATOM 1723 C GLUB 10 -3.658 -'.18.38031.416 1.0038.84 C

ATOM 1724 O GLUB 10 -4.543 -59.23531.467 1.0038.30 0 ATOM 1725 CB GLUB 10 -1.863 -58.31929.678 1.0041.81 C

ATOM 1726 CG GLUB 10 -1.656 -.59.81229.887 1.0047.49 C

ATOM 1727 CD GLUB 10 -2.600 -60.65629.061 1.0050.33 C

ATOM 1728 OE1 GLUB 10 -2.746 -60,37627.851 1.0052.58 0 ATOM 1729 OE2 GLUB 10 -3.188 -61.60629.619 1.0052.87 0 ATOM 1730 N GLUB 11 -3.030 -57.93032.498 1.0038.61 N

ATOM 1731 CA GLUB 11 -3.328 -58.47033.819 1.0038.56 C

ATOM 1732 C GLUB 11 -4.773 -58.25334.263 1.0037.80 C

ATOM 1733 O GLUB 11 -5.348 -59.10034.952 1.0037.00 0 ATOM 1734 CB GLUB 11 -2.370 -57.87834.851 1.0041.33 C

ATOM 1735 CG GLUB 11 -2.292 -58.67136.143 1.0045.17 C

A'POM1736 CD GLUB 11 -1.255 -58.11337.101 1.0048.43 C

A'POM1737 OE1 GLUB 11 -O.11B -57.83236.657 1.0047.49 0 ATOM 1738 OE2 GLUB 11 -1.577 -57.96138.298 1.0050.67 0 ATOM 1739 N GLUB 12 -5.359 ~-57.12033.889 1.0035.46 N

ATOM 1740 CA GLUB 12 -6.741 ~-56.85434.262 1.0034.08 C

ATOM 1741 C GLUB 12 -7.685 -57.81433.595 1.0034.20 C

ATOM 1742 O GLUB 12 -8.657 -58.29134.135 1.0032.51 0 ATOM 1743 CB GLUB 12 -7.139 -55.42133.918 1.0033.72 C

ATOM 1744 CG GLUB 12 -8.640 -55.22833.910 1.0032.44 C

P.,TOM1745 CD GLUB 12 -9.048 -53.83433.512 1.0033.30 C

ATOM 1746 OE1 GLUB 12 -10.185 -53.67733.010 1.0031.00 0 ATOM 1797 OE2GLU B 12 -8.240 -52.89933.711 1.0032.98 0 ATOM 1748 N VAL B 13 -7.404 -58.08032.269 1.0033.80 N

ATOM 1749 CA VAL B 13 -8.228 -58.99131.481 1.0035.28 C

ATOM 1750 C VAL B 13 -8.155 -60.40332.054 1.0035.86 C

ATUM 1751 0 VAL B 13 -9.159 -61.10532.123 1.0037.61 0 ATOM 1752 CB VAL B 13 -'1.782 -59.02829.999 1.0035.35 C

ATOM 1753 CG1VAL B 13 -8.562 -60.10629.245 1.0034.28 C

ATOM 1754 CG2VAL B 13 -8.016 -57.67329.352 1.0033.43 C

ATOM 1755 N THR B 14 -6.962 -60.81632.464 1.0037.22 N

ATOM 1756 CA THR B 14 -6.778 -62.14533.037 1.0038.21 C

ATOM 1757 C THR B 14 -7.566 -62.27234.335 1.0038.06 C

ATOM 1758 0 THR B 14 -8.273 -63.25434.550 1.0038.55 0 ATOM 1759 CB THR B 14 -5.294 -62.42333.331 1.0038.64 C

ATOM 1760 OG1THR B 14 -4.553 -62.39132.107 1.0039.16 0 ATOM 1761 CG2THR B 14 -5.124 -63.79433.981 1.0040.00 C

ATOM 1762 N LEU B 15 -7.438 -61.27335.201 1.0038.78 N

ATOM 1763 CA LEU B 15 -8.142 -61.27636.475 1.0039.49 C

ATOM 1764 C LEU B 15 -9.655 -61.33136.276 1.0040.11 C

ATOM 1765 O LEU B 15 -10.358 -62.06436.977 1.0040.31 0 A~POM1766 CB LEU B 15 -7.772 -60.02837.284 1.0040.61 C

ATOM 1767 CG LEU B 15 -6.327 -59.94937.785 1.0040.51 C

ATOM 1768 CDILEU B 15 -6.088 -58.60438.453 1.0040.90 C

A'POM1769 CD2LEU B 15 -6.061 -61.09138.760 1.0041.29 C

ATOM 1770 N LEU B 16 -10.156 -60.55535.321 1.0038.94 N

ATOM 1771 CA LEU B 16 -11.587 -60.53835.056 1.0038.18 C

ATOM 1772 C LEU B 16 -12.017 -61.82334.346 1.0038.79 C

ATOM 1773 0 LEU B 16 -13.080 -62.37834.640 1.0036.89 0 ATOM 1774 CB LEU B 16 -11.957 -59.31534.212 1.0037.15 C

ATOM 1775 CG LEU B 16 -11.832 -57.94234.887 1.0036.35 C

ATOM 1776 CD1LEU B 16 -12.097 -56.85233.864 1.0034.72 C

ATOM 1777 CD2LEU B 16 -12.818 -57.82836.045 1.0035.73 C

ATOM 1778 N ARG B 17 -11.189 -62.30333.422 1.0039.32 N

ATOM 1779 CA ARG B 17 -11.514 -63.53232.703 1.0041.55 C

ATOM 1780 C ARG B 17 -11.668 -64.70533.671 1.0041.62 C

i~TOM1781 0 ARG B 17 -12.551 -65.54333.498 1.0042.54 O

ATOM 1782 CB ARG B 17 -10.436 -63.86831.670 1.0040.79 C

.ATOM1783 CG ARG B 17 -10.734 -65.14930.896 1.0044.83 C

ATOM 1784 CD ARG B 17 -9.644 -65.98429.888 1.0048.13 C

ATOM 1785 NE ARGB 17 -8.319 -65.50530.501 1.0053.79 N

ATOM 1786 CZ ARGB 17 -7.954 -66.33031.479 1.0055.64 C

ATOM 1787 NH1 ARGB 17 -8.818 -67.21731.962 1.0056.51 N

ATOM 1788 NH2 ARGB 17 -6.728 -66.26031.984 1.0055.44 N

ATOM 1789 N ASPB 18 -10.813 - 64.75434.690 1.0041.31 N

ATOM 1790 CA ASPB 18 -10.860 -65.82935.678 1.0042.34 C

ATOM 1791 C ASPB 18 -12.108 -65.79236.555 1.0041.47 C

ATOM 1792 O ASPB 18 -12.472 -66.80237.152 1.0041.97 0 ATOM 1793 CB ASPB 18 -9.615 -65.78936.571 1.0043.99 C

ATOM 1794 CG ASPB 18 -8.341 -66.14135.820 1.0045.52 C

ATOM 1795 OD1 ASPB 18 -7.245 -66.01736.409 1.0047.29 0 ATOM 1796 OD2 ASPB 18 -8.430 -66.54434.642 1.0048.32 0 ATOM 1797 N LYSB 19 -12.768 -64.63936.632 1.0040.42 N

ATOM 1798 CA LYSB 19 -13.964 -F>4.51437.462 1.0039.47 C

ATOM 1799 C LYSB 19 -15.275 -64.76336.730 1.0039.15 C

ATOM 1800 0 LYSB 19 -16.316 -Ei4.93337.367 1.0039.35 0 ATOM 1801 CB LYSB 19 -14.013 -63.13338.119 1.0039.73 c ATOM 1802 CG LYSB 19 -12.846 -62.86739.055 1.0042.94 C

ATOM 1803 CD LYSB 19 -13.042 -61.60439.869 1.0043.88 C

ATOM 1804 CE LYSB 19 -11.922 -61.44640.891 1.0046.38 C

ATOM 1805 NZ LYSB 19 -12.164 -60.30441.818 1.0048.92 N

ATOM 1806 N ILEB 20 -15.231 -64.78535.400 1.0037.89 N

ATOM 1807 CA ILEB 20 -16.435 -65.01134.606 1.0036.68 C

ATOM 1808 C ILEB 20 -1.7.008-66.41734.812 1.0036.99 C

ATOM 1809 0 ILEB 20 -1.6.285-67.41234.747 1.0036.44 0 ATOM 1810 CB ILEB 20 -16.162 -64.79333.095 1.0036.54 C

ATOM 1811 CG1 ILEB 20 -15.845 -63.31532.826 1.0033.75 C

ATOM 1812 CG2 ILEB 20 -17.380 -65.22132.277 1.0034.93 C

A'POM1813 CD1 ILEB 20 -15.454 -63.01931.385 1.0031.97 C

ATOM 1814 N GLUB 21 -18.312 -66.47935.059 1.0037.20 N

ATOM 1815 CA GLUB 21 -19.019 -67.74135.280 1.0039.08 C

ATOM 1816 C GLUB 21 -19.584 -68.24333.948 1.0037.77 C

ATOM 1817 0 GLUB 21 -20.025 -67.44333.122 1.0036.83 O

ATOM 1818 CB GLUB 21 -20.147 -67.51.436.292 1.0041.55 C

ATOM 1819 CG GLUB 21 -19.651 -66.93737.624 1.0047.56 C

ATOM 1820 CD GLUB 21 -20.757 -66.30538.466 1.0051.63 C

ATOM 1821 OE1 B 21 -21.378 -65.31238.011 1.0050.03 0 GLU

ATOM 1822 OE2 B 21 -20.999 -66.80339.591 1.0054.40 0 GLU

ATO1H1823 N ASN B22 -19.578 -69.56133.750 1.0036.73 N

ATOM 1824 CA ASN B22 -20.066 -70.17132.510 1.0037.02 C

ATOM 1825 C ASN B22 -19.345 -69.51231.342 1.0037.65 C

ATOM 1826 0 ASN B22 -19.946 -69.18630.321 1.003?.82 O

ATOM 1827 CB ASN B22 -21.583 -69.98432.351 1.0036.60 C

ATOM 1828 CG ASN B22 -22.377 -70.70033.425 1.0036.00 C

ATOM 1829 OD1 ASN B22 -22.136 -71.87133.708 1.0038.87 0 ATOM 1830 ND2 ASN B22 -23.336 -70.00434.022 1.0034.67 N

ATOM 1831 N ARG B23 -18.039 -69.34531.498 1.0038.40 N

ATOM 1832 CA ARG B23 -17.225 -68.69030.495 1.0040.18 C

ATOM 1833 C ARG B23 -17.093 -69.40529,159 1.0040.61 C

ATOM 1834 0 ARG B23 -16.767 -70.58929.0$8 1.0039.75 O

ATOM 1835 CB ARG B23 -15.832 -68.42131.062 1.0041.62 C

ATOM 1836 CG ARG B23 -15.120 -E>7.26730.383 I.0045.88 C

ATOM 1837 CD ARG B23 -13.927 -67.73729.594 1.0047.65 C

ATOM 1838 NE ARG B23 -12.908 -68.31330.460 1.0049.89 N

ATOM 1839 CZ ARG B23 -11.747 -68.78230.019 1.0052.34 C

ATOM 1840 NH1 ARG B23 -11.466 -68.74028.722 1.0053.18 N

ATOM 1841 NH2 ARG B23 -10.867 -69.29430.871 1.0054.31 N

ATOM 1842 N GLN B24 -17.346 -68.6542$.096 1.0040.77 N

ATOM 1843 CA GLN B24 -17.232 -69.15626.736 1.0041.30 C

ATOM 1844 C GLN B24 -16.184 -68.27126.077 1.0041.02 C

ATOM 1845 0 GLN B24 -7.6.077-67.08826.401 1.0040.73 0 ATOM 1846 CB GLN B24 -18.571 -69.01626.004 1.0042.53 C

ATOM 1847 CG GLN B24 -19.694 -69.85526.600 1.0045.14 C

ATOM 1848 CD GLN B24 -I9.570 -71.32626.247 1.0047.08 C

A'rOM1849 OE1 GLN B24 -19.958 -7I.75125.157 1.0048.97 O

A'rOM1850 NE2 GLN B24 -19.017 -72.11027.163 1.0048.72 N

ATOM 1851 N THR B25 -15.401 -68.84325.171 1.0040.82 N

ATOM 1852 CA THR B25 -14.379 -68.08424.468 1.0040.78 C

ATOM 1853 C THR B25 -14.674 -68.10122.978 1.0041.54 C

ATOM 1$54 0 THR B25 -14.826 -69.16122.374 1.0039.95 0 ATOM 1855 CB THR B25 -12.978 -68.66724.704 1.0040.55 C

ATOM 1856 OG1 THR B25 -12.689 -68.64826.105 1.0041.14 0 ATOM 1857 CG2 THR B25 -11.922 -67.89523.964 1.0041.11 C

ATOM 1858 N ILE B26 -14.755 -66.91322.394 1.0042.22 N

ATOM 1859 CA ILE B26 -15.037 -66.76520.976 1.0042.93 C

ATOM 1860 C ILE B26 -13.795 -66.24320.268 1.0043.31 C

ATOM 1861 0 ILEB 26 -13.211 -65.24120.689 1.0043.26 0 ATOM 1862 CB ILEB 26 -16.193 -65.76820.763 1.0043.27 C

ATOM 1863 CG1 ILEB 26 -17.388 -66.17821.628 1.0045.19 C

ATOM 1864 CG2 ILEB 26 -16.588 -65.72519.297 1.0044.43 C

ATOM 1865 CD1 ILEB 26 -18.477 -65.13121.709 1.0045.98 C

ATOM 1866 N SERB 27 -13.390 -66.92519.201 1.0043.27 N

ATOM 1867 CA SERB 27 -12.221 -66.52118.428 1.0043.88 C

ATOM 1868 C SERB 27 -12.645 -65.95117.080 1.0094.03 C

ATOM 1869 0 SERB 27 -13.129 -66.68416.215 1.0043.86 0 ATOM 1870 CB SERB 27 -11.297 -67.71418.196 1.0044.84 C

ATOM 1871 OG SERB 27 -10.845 -68.24819.425 1.0048.87 O

ATUM 1872 N LEUB 28 -12.454 -64.64716.903 1.0043.27 N

ATOM 1873 CA LEUB 28 -12.823 -63.97815.658 1.0042.90 C

ATOM 1874 C LEUB 28 -1:1.731-fi3.01215.205 I.0042.62 C

ATC)M1875 O LEUB 28 -1:1,124-62.32216.022 1.0041.47 0 ATOM 1876 CB LEUB 28 -14.121 -63.19215.845 1.0044.39 C

ATOM 1877 CG LEUB 28 -15.373 -63.91516.337 1.0044.79 C

ATOM 1878 CD1 LEUB 28 -16.460 -62.89416,612 1.0045.83 C

ATOM 1879 CD2 LEUB 28 -15.834 -64.92115.305 1.0045.41 C

ATOM 1880 N GLYB 29 -11.492 -62.96813.897 1.0042.61 N

ATOM 1881 CA GLYB 29 '10.493 -62.07113.337 1.0042,03 C

ATOM 1882 C GLYB 29 -9.209 -61.88814.123 1.0041.88 C

ATOM 1883 O GLYB 29 -8.665 -60.78414.178 1.0041.70 0 ATOM 1884 N GLYB 30 -8.718 -62.96914.722 1.0040.97 N

ATOM 1885 CA GLYB 30 -7.486 -62.89915.4$8 1.0040.82 C

ATOM 1886 C GLYB 30 -7.666 -62.42016.918 1,0040.81 C

ATOM 1887 0 GLYB 30 -6.691 -62.28917.657 1.0041.53 O

A'.POM1888 N CYSB 31 -8.911 -62.16617.308 1.0039.80 N

A'POM1889 CA CYSB 31 -9.221 -61.69318.652 1.0039.27 C

A'POM1890 C CYSB 31 -9.937 --62.76719.447 1.0039.04 C

ATOM 1891 O CYSB 31 -10.509 ~-63.69618.880 1.0038.66 0 ATOM 1892 CB CYSB 31 -10.128 -60.45818.589 1.0038.25 C

ATOM 1893 SG CYSB 31 -9.488 -59.09717.600 1.0039.80 S

ATOM 1894 N GLUB 32 -9.906 -62.62820.768 1.0038.88 N

ATOM 1895 CA GLUB 32 -10.579 -63.56321.656 1.0038.59 C

ATOM 1896 C GLUB 32 -11.529 -62.79722.561 1.0037.15 C

ATOM 1897 0 GLUB 32 -11.134 -61.83623.221 1.0037.59 0 F,TOM1898 CB GLUH 32 -9.563 -64.33422.503 1.0040.15 C

ATOM 1899 CG GLU B 32 -9.168 -65.68521.914 1.0043.69 C

ATOM 1900 CD GLU B 32 -8.231 -66.46622.820 1.0045.35 C

ATCM 1901 OEl GLU B 32 -8.442 -66.44924.053 1.0047.00 0 ATOM 1902 OE2 GLU B 32 -7.292 -67.11022.301 1.0046.80 0 ATOM 1903 N ILE B 33 -12.787 -63.22022.578 1.0035.37 N

ATOM 1904 CA ILE B 33 -13.803 -62.58323.407 1.0033.98 C

ATOM 1905 C ILE B 33 -14.340 -63.59124.416 1.0034.79 C

ATOM 1906 0 ILE B 33 -14.768 -64.68724.042 1.0034.30 0 ATOM 1907 CB ILE B 33 -14.990 -62.09122.561 1.0032.47 C

ATOM 1908 CG1 ILE B 33 -14.509 -61.08421.512 1.0030.19 C

ATOM 1909 CG2 ILE B 33 -16.053 -61.50123.465 1.0031.08 C

ATOM 1910 CD1 ILE B 33 -15.623 -60.58020.601 1.0032.32 C

ATOM 1911 N TYR B 34 -14.329 -63.21825.692 1.0033.47 N

ATOM 1912 CA TYR B 34 -14.824 -64.10126.736 1.0033.65 C

ATOM 1913 C TYR B 34 -16.210 -63.63227.147 1.0033.76 C

ATOM 1914 0 TYR B 34 -16.413 -62.44627.426 1.0032.57 0 ATOM 1915 CB TYR B 34 -13.881 -64.06727.938 1.0033.15 C

ATOM 1916 CG TYR B 34 -12.429 -64.12927.544 1.0034.64 C

ATOM 1917 CD1 TYR B 34 -11.885 -65.28526.983 1.0035.02 C

ATOM 1918 CD2 TYR B 34 -11.604 -63.01227.683 1.0034.86 C

ATOM 1919 CE1 TYR H 34 -1Ø552-65.32426.564 1.0034.84 C

ATOM 1920 CE2 TYR B 34 -7Ø276-63.04127.270 1.0035.52 C

ATOM 1921 CZ TYR B 34 -9.758 -64.19726.711 1.0034.89 C

AmOM 1922 OH TYR B 34 -8.453 -64.21326.280 1.0034.89 0 A'.COM1923 N THR B 35 -17.169 -64.55427.158 1.0032.62 N

ATOM 1924 CA THR B 35 -18.530 -64.20827.546 1.0032.75 C

A'POM1925 C THR B 35 -18.961 --65.06428.722 1.0033.31 C

A'rOM1926 O THR B 35 -18.384 -66.11828.988 1.0032.05 0 ATOM 1927 CB THR B 35 -19.548 -64.40626.392 1.0034.15 C

ATOM 1928 OG1 THR B 35 -19.523 -65.77025.955 1.0031.85 0 ATOM 1929 CG2 THR B 35 -19.218 -63.48425.220 1.0032.43 C

ATOM 1930 N GLY B 36 -19.985 -64.59929.423 1.0033.26 N

ATOM 1931 CA GLY B 36 -20.470 -65.32230.577 1.0034.95 C

P.,TOM1932 G GLY B 36 -21.028 -64.32531.566 1.0034.36 C

P,TOM1933 0 GLY B 36 -21.464 -63.23931.178 1.0033.32 0 ATOM 1934 N GLN B 37 -21.014 -64.68532.844 1.0034.95 N

ATOM 1935 CA GLN B 37 -21.537 -63.80033.867 1.0035.56 C

ATOM 1936 C GLN B 37 -20.485 -63.41534.898 1.0036.34 C

ATOM 1937 O GLN B 37 -19.726 -64.25535.374 1.0036.13 0 ATOM 1938 CB GLN B 37 -22.729 -64.44934.589 1.0036.50 C

ATOM 1939 CG GLN B 37 -23.910 -64.82633.697 1.0035.79 C

ATOM 1940 CD GLN B 37 -23.741 -66.18833.059 1.0037.10 C

ATCM 1941 OE1GLN B 37 -23.601 -67.19333.754 1.0035.64 0 ATOM 1942 NE2GLN B 37 -23.750 -66.22931.731 1.0037.09 N

ATOM 1943 N LEU B 38 -20.438 -62.12835.217 1.0037.12 N

ATOM 1944 CA LEU B 38 -19.524 -61.61336.223 1.0037.89 C

ATUM 1945 C LEU B 38 -20.458 -62.33337.395 1.0038.16 C

ATOM 1946 0 LEU B 38 -21.305 -60.44137.326 1.0037.40 0 ATOM 1947 CB LEU B 38 -18.849 -60.31835.746 1.0037.43 C

ATOM 1948 CG LEU B 38 -17.798 -59.71836.693 1.0038.26 C

ATOM 1949 CD1LEU B 38 -16.718 -60.75337.001 1.0035.85 C

ATOM 1950 CD2LEU B 38 -17.182 -58.47836.062 1.0037.08 C

ATOM 1951 N ASN B 39 -20.318 -62.11938.955 1.0038.63 N

ATOM 1952 CA ASN B 39 -21.175 -61.98239.624 1.0039.78 C

ATOM 1953 C ASN B 39 -22.653 -61.88939.223 1.0039.53 C

ATOM 1954 0 ASN B 39 -23.388 -61.03539.720 1.0039.57 0 ATOM 1955 CB ASN B 39 -20.759 -60.75640.444 1.0040.65 C

ATOM 1956 CG ASN B 39 -19.316 -60.83540.905 1.0042.44 C

ATOM 1957 OD1ASN B 39 -18.906 -61.81441.535 1.0043.75 O

A7.'OM1958 ND2ASN B 39 -18.533 -59.80940.588 1.0043.25 N

A".uOM1959 N GLY B 40 -23.074 -62.76838.309 1.0039.11 N

ATOM 1960 CA GLY B 40 -24.463 -62.79337.870 1.0036.36 C

A'POM1961 C GLY B 40 -24.874 -61.87436.729 1.0036.67 C

ATOM 1962 0 GLY B 40 -26.021 --61.92536.271 1.0035.89 0 A'rOM1963 N THR B 41 -23.959 -61.02836.265 1.0035.76 N

ATOM 1964 CA THR B 4I -24.261 -60.10435.172 1.0034.02 C

ATOM 1965 C THR B 41 -23.619 -60.54333.863 1.0033.06 C

ATOM 1966 0 THR B 41 -22.927 -60.83933.820 1.0034.43 O

ATOM 1967 CB THR B 41 -23.759 -58.68035.493 1.0033.23 C

P,TOM1968 OG1THR B 41 -24.464 -58.17136.628 1.0032.21 O

ATOM 1969 CG2THR B 41 -23.980 -57.75534.312 1.0031.12 C

ATOM 1970 N GLU B 42 -24.407 -60.58132.792 1.0032.85 N

ATOM 1971 CA GLU B 42 --23.874-60.97431.487 1.0032.09 C

ATOM 1972 C GLU B 42 -22.824 -59.95932.043 1.0031.24 C

ATOM 1973 0 GLU B 42 -23.097 -58.75631.002 2.0030.34 0 ATOM 1974 CB GLU B 42 -24.988 -61.01630.433 2.0032.43 C

ATOt91975 CG GLUB 42 -?.6,109-62.03430.6811.00 32.43 C

ATOM 1976 CD GLUB 42 -25.666 -63.47130.4921.00 33.97 C

ATOM 1977 OE1 GLUB 42 -26.545 -64.35730.4461.00 34.74 0 ATOM 1978 OE2 GLUB 42 -29.446 -63.72530.3921.00 33.71 O

ATOM 1979 N VALB 43 -21.631 -60.44530.7171.00 30.64 N

ATOM 1980 CA VALB 43 -20.549 -59.58930.2561.00 30.27 C

ATOM 1981 C VALB 43 -19.865 -60.17929.0191.00 31.24 C

ATOM 1982 0 VAL8 43 -20.023 -61.36528.7111.00 30.95 0 ATOM 1983 CB VALB 43 -19.464 -59.39831.3561.00 29.24 C

ATOM 1984 CG1 VALB 43 -20.070 -58.70432.5601.00 29.07 C

ATOM 1985 CG2 VALB 43 -18.876 -60.74431.7661.00 27.41 C

ATOM 1986 N ALAB 44 -19.126 -59.33728.3031.00 29.12 N

ATOM 1987 CA ALAB 44 -18,372 -59.75927.1261.00 29.21 C

ATUM 1988 C ALAB 44 -17.026 -59.05527.2811.00 28.59 C

ATOM 1989 0 ALAB 44 -16.952 -57.83427.2201.00 29.05 0 ATOM 1990 CB ALAB 44 -19.071 -59.31125.8571.00 30.82 C

ATOM 1991 N LEUB 45 -15.973 -59.83527.4941.00 28.75 N

ATOM 1992 CA LEUB 45 -14.627 -59.31427.7281.00 29.06 C

ATOM 1993 C LEUB 45 -13.646 -59.50026.5771.00 30.00 C

ATOM 1994 0 LEUB 45 -13.574 -60.57225.9701.00 30.23 0 ATOM 1995 CB LEUB 45 -14.054 -59.96828.9901.00 27,21 C

ATOM 1996 CG LEUB 45 -12.616 -59.67529.4281.00 28.82 C

ATOM 1997 CD1 LEUB 45 -12.499 -58.23329.8721.00 27.36 C

ATOM 1998 CD2 LEUB 45 -12.236 -60.61330.5801.00 27.37 C

ATOM 1999 N LEUB 46 -12.873 -58.45326.2991.00 28.41 N

ATOM 2000 CA LEUB 46 -11.888 -58.48325.2241.00 28.63 C

ATOM 2001 C LEUB 46 -10.684 -57.59925.5601.00 28.19 C

ATOM 2002 0 LEUB 46 -10.845 -56.53226.1461.00 26.91 0 ATOM 2003 CB LEUB 46 -12.534 -57.98223.9251.00 29.59 C

A'.COM2004 CG LEUB 46 -11.603 -57.53722.7931.00 31.10 C

A'fOM2005 CD1 LEUB 96 -11.064 -58.75022.0491.00 30.94 C

A'POM2006 CD2 LEUB 46 -12.374 --56.62$21.8421.00 31.82 C

ATOM 2007 N LYSB 47 -9.484 -58.05025.2041.00 27.82 N

ATOM 2008 CA LYSB 47 -8.280 -57.25625.9431.00 30.26 C

ATOM 2009 C LYSB 47 -8.041 -56.43424.1831.00 30.22 C

ATOM 2010 0 LYSB 47 -7.985 '56.98123.0781.00 30.66 0 ATOM 2011 CB LYSB 47 -7.060 '58.14025.7061.00 31.18 C

ATOM 2012 CG LYSB 47 -5.793 -57.30825.9151.00 34.72 C

ATOM 2013 CD LYS B 47 -4.563 -58.15126.136 1.0038.89 C

ATOM 2014 CE LYS B 47 -3.331 -57.26226.252 1.0040.78 C

ATCM 2015 NZ LYS B 47 -2.085 -58.05326.465 1.0042.96 N

ATOM 2016 N SER B 48 -7.901 -55.12424.338 1.0029.95 N

ATOM 2017 CA SER B 48 -7.704 -54.26023.178 1.0029.53 C

ATOM 2018 C SER B 48 -6.335 -54.39022.525 1.0030.37 C

ATOM 2019 0 SER B 48 -5.325 -54.61123.199 1.0029.42 0 ATOM 2020 CB SER B 48 -7.946 -52.79923.563 1.0031.96 C

ATOM 2021 OG SER B 48 -'1.132 -52.41924.657 1.0033.00 0 ATOM 2022 N GLY B 49 -6.312 -54.25721.201 1.0030.63 N

ATOM 2023 CA GLY B 49 -5.062 -54.33220.468 1.0030.67 C

ATOM 2024 C GLY B 49 -4.361 -52.98620.549 1.0030.16 C

ATOM 2025 0 GLY B 49 -4.895 -52.04621.145 1.0030.72 0 ATOM 2026 N ILE B 50 -3.181 -52.88819.944 1.0028.96 N

ATOM 2027 CA ILE B 50 -2.388 -:51.66119.955 1.0028.44 C

ATOM 2028 C ILE B 50 -2.651 -50.79418.725 1.0027.34 C

ATOM 2029 0 ILE B 50 -2.448 -51.23917.594 1.0027.57 0 ATOM 2030 CB ILE B 50 -0.875 -51.98219.979 1.0029.73 C

ATOM 2031 CG1 ILE B 50 -0.554 -52.92421.143 1.0031.58 C

ATOM 2032 CG2 ILE B 50 -0.066 -50.69020.079 1.0027.91 C

ATOM 2033 CD1 ILE B 50 -0.967 -52.38422.506 1.0034.21 C

ATOM 2034 N GLY B 51 -3.071 -49.55418.946 1.0026.18 N

ATOM 2035 CA GLY B 51 -3.329 -48.66317.824 1.0025.63 C

ATOM 2036 C GLY B 51 -4.803 -48.56017.503 1.0025.27 C

A'POM2037 0 GLY B 51 -5.596 -49.41917.903 1.0026.22 0 ATOM 2038 N LYS B 52 -5.171 --47.52616.749 1.0024.05 N

ATOM 2039 CA LYS B 52 -6.567 --47.28416.403 1.0024.30 C

ATOM 2040 C LYS B 52 -7.249 -48.38615.592 1.0023.95 C

ATOM 2041 0 LYS B 52 -8.357 -48.79915.915 1.0024.61 0 ATOM 2092 CB LYS B 52 -6.682 -45.94315.670 1.0026.08 C

ATOM 2043 CG LYS B 52 -5.933 -44.83116.395 1.0031.44 C

ATOM 2044 CD LYS B 52 -6.402 -93.42216.032 1.0039.92 C

P,TOM2045 CE LYS B 52 -6.254 -43.09214.563 1.0033.69 C

F,TOM2096 NZ LYS B 52 -6.305 -41.61514.378 1.0031.53 N

ATOM 2047 N VAL B 53 -6.592 -48.86514.547 1.0022.98 N

ATOM 2048 CA VAL B 53 -7.175 -49.90013.704 1.0023.63 C

ATOM 2049 C VAL B 53 -7.334 -51.23714.414 1.0023.32 C

ATOM 2050 0 VAL B 53 -8.383 -51.86914.299 1.0025.26 O

ATOM 2051 CB VAL B 53 -6.352 -50.07812.393 1.0022.90 C

ATCM 2052 CG1 VAL B 53 -6.857 -51.27111.593 1.0022.49 C

ATOM 2053 CG2 VAL B 53 -6.493 -48.82311.539 1.0021.20 C

ATOM 2054 N ALA B 54 -6.312 -51.67315.147 1.0023.81 N

ATOM 2055 CA ALA B 54 -6.403 -52.94515.859 1.0029.99 C

ATOM 2056 C ALA B 54 -7.474 -52.85016.930 1.0025.22 C

ATOM 2057 O ALA B 54 -8.237 -53.79517.142 1.0025.50 0 ATOM 2058 CB ALA B 54 -5.059 -53.30816.491 1.0025.51 C

ATOM 2059 N ALA B 55 -7.526 -51.71017.617 1.0024.20 N

ATOM 2060 CA ALA B 55 -8.523 -51.51418.656 1.0024.67 C

ATOM 2061 C ALA B 55 -9.920 -51.50418.028 1.0024,67 C

ATOM 2062 0 ALA B 55 -10.846 -52,12818.552 1.0024.61 0 ATOM 2063 CB ALA B 55 -8.265 -50.20519.394 1.0025.71 C

ATOM 2064 N ALA B 56 -10.065 -50.79916.906 1.0022.68 N

ATOM 2065 CA ALA B 56 -11.350 -50.70916.219 1.0022.83 C

ATOM 2066 C ALA B 56 -11.815 -52.06715.718 1.0022.83 C

ATOM 2067 O ALA B 56 -13.010 '52.36615.727 1.0022.63 0 ATOM 2068 CB ALA B 56 -11.256 -49.73915.049 1.0022.79 C

ATOM 2069 N LEU B 57 -10.870 -52.88815.281 1.0023.55 N

ATOM 2070 CA LEU B 57 -11.201 -54.21014.771 1.0025.55 C

ATOM 2071 C LEU B 57 -11.843 -55.05315.869 1.0025.98 C

ATOM 2072 0 LEU B 57 -12.927 -55.60915.675 1.0025.54 0 ATOM 2073 CB LEU B 57 -9.939 -54.88514.239 1.0024.46 C

ATOM 2074 CG LEU B 57 -10.057 -56.15713.397 1.0025.25 C

ATOM 2075 CDl LEU B 57 -8.700 -56.44912.768 1.0023.89 C

A'~OM2076 CD2 LEU B 57 -10.515 -57.33514.262 1.0025.18 C

A'rOM2077 N GLY B S8 -11.175 -55.14417.017 1.0026.60 N

A'POM2078 CA GLY B 58 -11.709 -55.91918.128 1.0026.60 C

ATOM 2079 C GLY B 58 -13.045 -55.39518.626 1.0027.12 C

ATOM 2080 O GLY B 58 -13.994 -56.16018.840 1.0028.19 0 ATOM 2081 N ALA B 59 -13.131 -54.08218.813 1.0026.25 N

ATOM 2082 CA ALA B 59 -14.371 -53.47219.286 1.0024.87 C

ATOM 2083 C ALA B 59 -15.537 -53.76618.343 1.0024.07 C

ATOM 2084 O ALA B 59 -16.655 -54.05218.790 1.0022.66 0 ATOM 2085 CB ALA B 59 -14.184 -51.96119.435 1.0023.38 C

ATOM 2086 N THR B 60 -15.280 -53.68817.039 1.0023.38 N

ATOM 2087 CA THR B 60 -16.319 -53.94416.044 1.0024.70 C

ATOM 2088 C THR B 60 -16.841 -55.37816.153 1.0026.02 C

ATOM 2089 O THRB 60 -18.044 -55.61316.0681.00 27.05 O

ATOM 2090 CB THRB 60 -15.797 -53.66914.6171.00 24.67 C

ATOP9 2091 OG1 THRB 60 -15.997 -52.27114.4931.00 24.77 0 ATOM 2092 CG2 THRB 60 -16.845 -54.03713.5651.00 23.13 C

ATOM 2093 N LEUB 61 -15.942 -56.33416.3541.00 26.80 N

ATOM 2094 CA LEUB 61 -16.355 -57.72616.4851.00 27.81 C

ATOM 2095 C LEUB 61 -17.210 -57.93417.7311.00 28.48 C

ATOM 2096 O LEUB 61 -18.233 -58.61717.6851.00 28.72 0 ATOM 2097 CB LEUB 61 -15.130 -58.64016.5551.00 27.02 C

ATOM 2098 CG LEUB 61 -14.323 -58.74615.2621.00 28.84 C

ATOM 2099 CD1 LEUB 61 -13.101 -59.63215.4891.00 28.28 C

ATOM 2100 CD2 LEUB 61 -15.204 -59.31414.1591.00 29.22 C

ATOM 2101 N LEUB 62 -16.792 -57.34318.8441.00 27.46 N

ATOM 2102 CA LEUB 62 -17.525 -57.49420.0911.00 28.08 C

ATGM 2103 C LEUB 62 -18.907 -56.85720.0351.00 28.83 C

ATOM 2104 0 LEUB 62 -19.892 -57.46420.4611.00 28.62 0 ATOM 2105 CB LEUB 62 -16.713 -56.90621.2521.00 30.03 C

ATC)M 2106 CG LEUB 62 -17.228 -57.18422.6691.00 31.51 C

ATOM 2107 CD1 LEUB 62 -16.068 -57.13223.6451.00 34.58 C

ATOM 2108 CD2 LEUB 62 -18.303 -56.17823.0471.00 32.49 C

ATOM 2109 N LEUB 63 -18.991 -55.64719.4931.00 28.30 N

ATOM 2110 CA LEUB 63 -20.269 -:14.95119.4071.00 30.31 C

AT(7M 2111 C LEUB 63 -21.284 -55.67418.5291.00 32.58 C

ATOM 2112 0 LEUB 63 -22.463 -55.75418.8761.00 32.62 0 ATOM 2113 CB LEUB 63 -20.062 -!i3.S1918.8931.00 30.34 C

ATOM 2114 CG LEUB 63 -19.489 -52.54819.9351.00 31.63 C

ATOM 2115 CD1 LEUB 63 -19.297 -51.16719.3371.00 32.74 C

ATOM 2116 CD2 LEUB 63 -20.440 -52.47721.1171.00 32.65 C

ATOM 2117 N GLUB 64 -20.816 -56.20817.4041.00 33.74 N

ATOM 2118 CA GLUB 64 -21.665 -56.92216.4541.00 36.76 C

ATOM 2119 C GLUB 64 -22.078 -58.31116.9161.00 36.09 C

ATOM 2120 0 GLUB 64 -23.244 -58.68716.8371.00 36.25 0 ATOM 2121 CB GLUB 64 -20.945 -57.06515.1121.00 38.24 C

ATOM 2122 CG GLUB 64 -21.663 -56.40313.9711.00 44.44 C

ATOM 2123 CD GLUB 64 -23.104 -56.83413.8661.00 45.18 C

A'.COM2124 OE1 GLUB 64 -23.352 -58.02513.5871.00 47.31 0 A'.COM2125 OE2 GLUB 64 -23.989 --55.97514.0671.00 46.90 O

A'COM 2126 N HISB 65 -21.103 -59.07317.3821.00 36.81 N

ATOM 2127 CA HIS B 65 -21.335 -60.43017.832 1.0038.38 C

ATOM 2128 C HIS B 65 -22.066 -60.53219.173 1.0038.70 C

ATGM 2129 O HIS B 65 -22.939 -61.37919.338 1.0039.18 0 ATOM 2130 CB HIS B 65 -19.994 -61.15617.926 1.0040.59 C

ATC)M2131 CG HIS B 65 -20.120 -62.63218.134 1.0044.55 C

ATOM 2132 ND1 HIS B 65 -20,278 -63,51817.092 1.0046.43 N

ATOM 2133 CD2 HIS B 65 -20.131 -63.37519.266 1.0045.64 C

ATOM 2134 CE1 HIS B 65 -20.379 -64.74517.572 1.0046.79 C

ATOM 2135 NE2 HIS B 65 -20.293 -fi4.68518.88$ 1.0045.33 N

ATOM 2136 N CYS B 66 -21.727 -59.66120.123 1.0037.87 N

ATOM 2137 CA CYS B 66 -22.337 -59.71921.451 1.0036.68 C

ATOM 2138 C CYS B 66 -23.469 -58.74321.752 1.0035.62 C

ATOM 2139 O CYS B 66 -24.202 -58.93622.715 1.0036.97 0 ATOM 2140 CB CYS B 66 -21.251 -59.56822.516 1.0035.97 C

ATOM 2141 SG CYS B 66 -19.909 -60.75022.343 1.0038.24 S

ATOM 2142 N LYS B 67 -23.618 -57.69620.952 1.0035.88 N

ATOM 2143 CA LYS B 67 -29.689 -56.72921.186 1.0036.84 C

ATOM 2144 C LYS B 67 -24.797 -56.24822.641 1.0036.34 C

ATOM 2145 0 LYS B 67 -25.858 -56.35923.258 1.0035.51 0 ATOM 2196 CB LYS B 67 -26.039 -57.32620.775 1,0039,93 C

ATOM 2147 CG LYS B 67 -26.581 -56.84419.436 1.0043.16 C

ATOM 2148 CD LYS B 67 -25.810 -57.42018.270 1.0046.19 C

ATOM 2149 CE LYS B 67 -26.507 -57.09916.951 1.0047.54 C

A".'OM2150 NZ LYS B 67 -25.859 -57.78515.798 1.0048.39 N

A'IOM2151 N PRO B 68 -23.707 -55.70823.209 1.0034.76 N

A'POM2152 CA PRO B 68 -23.779 -55.23724.596 1.0033.39 C

A'rOM2153 C PRO B 68 -24.611 -53.95924.698 1.0033.22 C

ATOM 2154 0 PRO B 68 -24.738 -53.21523.729 1.0034.29 0 ATOM 2155 CB PRO B 68 -22.316 -55.00524.947 1.0033.95 C

ATOM 2156 CG PRO B 68 -21.758 -54.50723.640 1.0032.71 C

ATOM 2157 CD PRO B 68 -22.365 -55.47422.643 1.0034.73 C

ATOM 2158 N ASP B 69 -25.180 -53.70625.872 1.0032.82 N

ATOM 2159 CA ASP B 69 -25.982 -52.50826.073 1.0031.49 C

F,TOM2160 C ASP B 69 -25.085 -51.32126.372 1.0030.95 C

F,TOM2161 0 ASP B 69 -25.446 -50.17526.097 1.0030.80 0 ATOM 2162 CB ASP B 69 -26.967 -52.71427.221 1.0033.51 C

ATOM 2163 CG ASP B 69 -27.965 -53.81126.926 1.0035.52 C

ATOM 2164 OD1 ASP B 69 -27.892 -54.87827.567 1.0034.51 O

ATOM2165 OD2ASP B 69 -28.810 -53.60526.031 1.0036.54 0 ATOM2166 N VAL B 70 -23.916 -51.60026.941 1.0029.45 N

ATOM2167 CA VAL B 70 -22.954 -50.55227.262 1.0028.35 C

ATOM2168 C VAL B 70 -21.540 -51.09327.113 1.0028.06 C

ATOM2169 O VAL B 70 -21.323 -52.30627,081 1.0026.57 0 ATOM2170 CB VAL B 70 -23.136 -50.01228.716 1.0028.75 C

ATOM2171 CG1VAL B 70 -24.541 -99.44528.901 1.0028.28 C

ATC)M2172 CG2VAL B 70 -22.880 -51.10929.720 1.0029.46 C

ATOM2173 N ILE B 71 -20.584 -50.18127.008 1.0027.17 N

ATOM2174 CA ILE B 71 -19.178 -50.53726.872 1.0027.35 C

ATOM2175 C ILE B 71 -18.345 -X19.84727.942 1.0027.59 C

ATOM2176 0 ILE B 71 -18.475 -48.63628.161 1.0028.20 0 ATOM2177 CB ILE B 71 -18.611 -50.11825.482 1.0027.22 C

ATOM2178 CG1ILE B 71 -19.045 -51.12124.413 1.0025.45 C

ATOM2179 CG2ILE B 71 -17.084 -50.03425.533 1.0025.49 C

ATOM2180 CD1ILE B 71 -18.405 -52.49224.567 1.0026.72 C

ATOM2181 N ILE B 72 -17.504 -50.62328.617 1.0026.09 N

ATOM2182 CA ILE B 72 -16.601 -50.08129.626 1.0027.26 C

ATOM2183 C ILE B 72 -15.228 -50.31629.018 1.0027.47 C

ATOM2184 0 ILE B 72 -14.854 -51.45928.742 1.0028.50 0 ATOM2185 CB ILE B 72 -16.679 -50.83930.982 1.0025.92 C

ATOM2186 CG1ILE B 72 -18.063 -50.65631.616 1.0026.85 C

A'COM2187 CG2ILE B 72 -15.594 -50.31531.927 1.0027.09 C

ATOM2188 CD1ILE B 72 -18.290 -51.52232.855 1.0027.67 C

ATOM2189 N ASN B 73 -14.487 --49.23728.799 1.0026.72 N

ATOM2190 CA ASN B 73 -13.165 -49.32628.196 1.0025.90 C

ATOM2191 C ASN B 73 -12.082 '48.85329.164 1.0025.94 C

ATOM2192 0 ASN B 73 -12.012 -47.67029.498 1.0026.96 0 ATOM2193 CB ASN B 73 -13.143 -48.47826.923 1.0023.98 C

P,TOM2194 CG ASN B 73 -11.800 -48.49326.236 1.0025.65 C

ATOM2195 OD1ASN B 73 -11.354 -47.47325.713 1.0026.03 0 ATOM2196 ND2ASN B 73 -11.147 -49.65426.220 1.0023.13 N

ATOM2197 N THR B 74 -11.230 -99.77329.597 1.0025.11 N

ATOM2198 CA THR B 74 -10.166 -49.45030.546 1.0025.93 C

ATOM2199 C THR B 74 -8.762 -49.59029.969 1.0026.37 C

ATOM2200 0 THR B 74 -8.555 -50.19828.915 1.0025.01 0 ;.TOM2201 CB THR B 74 -10.217 -50.37331.759 1.0025.72 C

ATOM2202 OGlTHR B 74 -10.026 -51.71631.307 1.0025.06 0 ATOhf2203 CG2THR B 74 -11.550 -50.25332.486 1.0023.01 C

ATOM 2204 N GLY B 75 -7.793 -99.04730.698 1.0024.30 N

ATOM 2205 CA GLY B 75 -6.413 -49.11630.264 1.0025.10 C

ATOM 2206 C GLY B 75 -5.572 -48.11831.029 1.0025.58 C

ATOPd2207 0 GLY B 75 -5,922 -47.73032.147 1.0025.22 0 ATOM 2208 N SER B 76 -4,456 -4.'.70930.434 1.0026.26 N

ATOM 2209 CA SER B 76 -3.573 -46.73331.062 1.0027.21 C

ATOM 2210 C SER B 76 -3.241 -45.65530.045 1.0027.40 C

ATOM 2211 0 SER B 76 -3.445 -45.83928.847 1.0027.69 0 ATOM 2212 CB SER B 76 -2.287 -47.40331.569 1.0028.51 C

ATOM 2213 OG SER B 76 -1.515 -4'7.93730.508 1.0029.67 0 ATOM 2214 N ALA B 77 -2.741 -44.52230.521 1.0027.34 N

ATOM 2215 CA ALA B 77 -2.398 -4:3.42829.631 1.0028.12 C

ATOM 2216 C ALA B 77 -1.341 -42.52730.262 1.0028.51 C

ATOM 2217 0 ALA B 77 -0.998 -42.68131.435 1.0028.55 0 ATOM 2218 CB ALA B 77 -3.650 -42.61229.313 1.0024.06 C

ATOM 2219 N GLY B 78 -0.819 -41.60629.462 1.0028.46 N

ATOM 2220 CA GLY B 78 0.164 -40.66029.952 1.0028.14 C

ATOM 2221 C GLY B 78 -0.612 -39.42730.370 1.0028.61 C

ATOM 2222 0 GLY B 78 -1.559 -39.03429.684 1.0029.39 0 ATOM 2223 N GLY B 79 -0.236 -38.82831.495 1.0028.94 N

ATOM 2224 CA GLY B 79 -C).925 -37.64231.968 1.0029.42 C

ATOM 2225 C GLY B 79 -0.431 -36.37731.297 1.0030.96 C

ATOM 2226 0 GLY B 79 0.766 -?.6.20631.072 1.0031.88 0 ATOM 2227 N LEU B 80 -1.360 -35.48930.965 1.0031.35 N

ATOM 2228 CA LEU B 80 -1.024 -34.22930.328 1.0031.82 C

ATOM 2229 C LEU B 80 -1.214 -33.06431.291 1.0032.94 C

ATOM 2230 0 LEU B 80 -0.445 -x2.11031.260 1.0033.29 0 ATOM 2231 CB LEU B 80 -1.886 -34.02029.079 1.0031.65 C

ATOM 2232 CG LEU B 80 -1.295 -34.29427.691 1.0032.96 C

ATOM 2233 CD1LEU B 80 -0.161 -35.28327.741 1.0032.52 C

ATOM 2234 CD2LEU B 80 -2.414 -34.79426.794 1.0033.95 C

ATOM 2235 N ALA B 81 -2.233 -33.13432.142 1.0033.10 N

ATOM 2236 CA ALA B 81 -2.469 -32.05433.100 1.0035.16 C

ATOM 2237 C ALA B 81 -1.340 -32.01539.136 1.0035.70 C

ATOM 2238 0 ALA B 81 -0.870 -33.05934.602 1.0033.71 0 ATOM 2239 CB ALA B 81 -3.826 -32.23933.795 1.0034.33 C

ATOM 2240 N PRO B 82 -0.881 -30.80734.499 1.0037.59 N

ATOM 2241 CA PROB 82 0.198 -30.64535.479 1.0038.62 C

ATOM 2242 C PROB 82 -0.179 -31,11836.877 1.0038.83 C

ATOM 2243 O PROB 82 0.687 -31.49537.666 1.0039.78 O

ATCM 2244 CB PROB 82 0.481 -29.14735.430 1.0038.95 C

ATOM 2245 CG PROB 82 -0.865 -28.56835.131 1.0040.48 C

ATGM 2246 CD PROB 82 -1.364 -29.49334.034 1.0038.47 C

ATOM 2247 N THRB 83 -1..472 -31.11337.180 1.0038.70 N

ATOM 2248 CA THRB 83 -7..933 -31.53938.496 1.0038.84 C

ATOM 2249 C THRB 83 -2.131 -33.04538.621 1.0038.44 C

ATOM 2250 0 THRB 83 -2.359 -33.55539.718 1.0038.03 0 ATOM 2251 CB THRB 83 -3.240 -30.81538.884 1.0039.65 C

ATOM 2252 OG1 THRB 83 -4.172 -30.88737.795 1.0039.38 0 ATOM 2253 CG2 THRB 83 -2.953 -29.34939.217 1.0039.72 C

ATOM 2254 N LEUB 84 -2.044 -33.75837.501 1.0038.15 N

ATOM 2255 CA LEUB 84 -2.193 -35.21037.516 1.0039.18 C

ATOM 2256 C LEUB 84 -0.927 -35.86238.047 1.0041.07 C

ATOM 2257 0 LEUB 84 0.179 -35.36737.818 1.0041.59 O

ATOM 2258 CB LEUB 84 -2.447 -35.75936.111 1.0037.34 C

ATOM 2259 CG LEUB 84 -3.$40 -35.64635.503 1.0036.34 C

ATOM 2260 CD1 LEUB 84 -3.807 -36.21634.095 1.0035.30 C

ATOM 2261 CD2 LEUB 84 -4.845 -36.39836.365 1.0035.04 C

ATOM 2262 N LYSB 85 -1.096 -36.97938.747 1.0041.01 N

ATOM 2263 CA LYSB B5 0.030 -37.71839.292 1.0042.46 C

ATOM 2264 C LYSB 85 -0.152 -39.18738.947 1.0042.80 C

ATOM 2265 0 LYSB 85 -1.277 -39.65338.734 1.0043.29 0 A7:'OM2266 CB LYSB 85 0.095 -37.55440.809 1.0044.95 C

ATOM 2267 CG LYSB 85 -1.142 -38.06041.533 1.0047.29 C

ATOM 2268 CD LYSB 85 -1.046 -37.83643.036 1.0049.34 C

A'.~OM2269 CE LYSB 85 -2.382 -38.12143.713 1.0050.62 C

A'POM2270 NZ LYSB 85 -3.482 -37.28243.135 1.0048.77 N

A'POM2271 N VALB 86 0.953 --39.91738.879 1.0041.50 N

ATOM 2272 CA VALB 86 0.877 -41.33438.570 1.0041.24 C

ATOM 2273 C VALB 86 -0.094 -41.94939.564 1.0040.29 C

ATOM 2274 0 VALB 86 -0.079 -41.60440.792 1.0040.29 0 ATOM 2275 CB VALB 86 2.255 -42.00838.708 1.0040.83 C

ATOM 2276 CG1 VALB 86 2.150 -43.49038.374 1.0040.81 C

ATOM 2277 CGZ VALB 86 3.248 -41.32237.788 1.0040.24 C

ATOM 2278 N GLYB 87 -0.955 -42.83939.086 1.0039.54 N

ATOM 2279 CA GLYB 87 -1.915 -43.46639.972 1.0037.70 C

ATOM 2280 C GLYB 87 -3.309 -42.88539.856 1.0037.50 C

ATOM 2281 0 GLYB 87 -4.281 -43.58540.124 1.0038.30 0 ATOM 2282 N ASPB 88 -3.424 -41.61339.478 1.0036.99 N

ATOM 2283 CA ASPB 88 -4.745 -41.00839.331 1.0036.37 C

ATOM 2284 C ASPB 88 -5.488 -41.77338.253 1.0035.89 C

ATOM 2285 0 ASPB 88 -4.867 -42.39737.397 1.0035.24 0 ATOM 2286 CB ASPB 88 -4.652 -39.54338.905 1.0038.19 C

ATC)M2287 CG ASPB 88 -4.208 -38.63240.025 1.0039.61 C

ATOM 2288 OD1 ASPB 88 -4.198 -39.07841.190 1.0040.17 0 ATOM 2289 OD2 ASPB 88 -3.879 -37.46439.735 1.0039.27 0 ATOM 2290 N ILEB 89 -6.815 -41.72038.292 1.0035.57 N

ATOM 2291 CA ILEB 89 -'7.629 -42.41137.302 1.0034.11 C

ATOM 2292 C ILEB 89 -8.475 -41.91236.532 1.0033.18 C

ATOM 2293 0 ILEB 89 -9.386 -40.79437.093 1.0033.53 0 ATOM 2294 CB ILEB 89 -8.578 -43.43637.955 1.0035.02 C

ATOM 2295 CG1 ILEB 89 -7.782 -44.44138.797 1.0035.08 C

ATOM 2296 CG2 ILEB 89 -9.367 -.44.16036.872 1.0032.68 C

ATOM 2297 CD1 ILEB 89 -6.788 -95.25538.001 1.0036.18 C

ATOM 2298 N VALB 90 -8.184 -41.25635.246 1.0031.27 N

ATOM 2299 CA VALB 90 -8.937 -40.32234.417 1.0029.92 C

ATOM 2300 C VALB 90 -10.180 -40.98333.830 1.0028.81 C

ATOM 2301 0 VALB 90 -1Ø123-42.09933.321 1.0027.60 O

ATOM 2302 CB VALB 90 -8.061 -39.77233.263 1.0030.81 C

ATOM 2303 CG1 VALB 90 -8.910 -38.95332.294 1.0031.89 C

ATOM 2309 CG2 VALB 90 -6.940 -38.90633.836 1.0032.29 C

ATOM 2305 N VALB 91 -11.311 -40.29833.938 1.0028.14 N

A'POM2306 CA VALB 91 -12.561 -40.79733.386 1.0028.40 C

A'POM2307 C VALB 91 -12.885 -39.82132.271 1.0029.15 C

ATOM 2308 0 VALB 91 -12.942 -38.60932.491 1.0029.56 0 ATOM 2309 CB VALB 91 -13.705 -40.78334.422 1.0028.51 C

ATOM 2310 CG1 VALB 91 -14.973 ~-41.37233.800 1.0027.08 C

ATOM 2311 CG2 VALB 91 -13.307 -91.57835.650 1.0028.35 C

ATOM 2312 N SERB 92 -13.080 -40.34031.069 1.0027.86 N

ATOM 2313 CA SERB 92 -13.369 -39.47829.937 1.0028.76 C

P.TOM2314 C SERB 92 -14.769 -38.90229.934 1.0029.29 C

F,TOM2315 0 SERB 92 -15.732 -39.57130.288 1.0029.92 0 F~TOM2316 CB SERB 92 -13.175 -40.23928.623 1.0028.99 C

ATOM2317 OG SER B 92 -14.130 -41.28628.506 1.00 31.16 0 ATOM2318 N ASP B 93 -14.875 -37.64129.549 1.00 30.25 N

ATOM2319 CA ASP B 93 -16.179 -3T.09229.402 1.00 32.15 C

ATOM2320 C ASP B 93 -16.295 -36.94727.883 1.00 31.48 C

ATOM2321 O ASP B 93 -17.385 -36.81127.321 1.00 32.71 0 ATOM2322 CB ASP B 93 -16.244 -35.65930.060 1.0O 35.93 C

ATOM2323 CG ASP B 93 -15.132 -31.73629.612 1.00 38.87 C

ATOM2324 OD1ASP B 93 -15.186 -33.54729.986 1.00 43.89 0 ATOM2325 OD2ASP B 93 -14.207 -35.18228.901 1.00 91.33 0 ATOM2326 N GLU B 94 -15.149 -3'7.08327.224 1.00 28.99 N

ATOM2327 CA GLU B 94 -15.082 -36.99025.773 1.00 29.69 C

ATOM2328 C GLU B 94 -13.758 -37.57625.275 1.00 28.43 C

ATOM2329 0 GLU B 94 -12.779 -37.61426.024 1.00 28.00 0 ATOM2330 CB GLU B 94 -15.185 -35.51225.397 1.00 32.79 C

ATOM2331 CG GLU B 94 -15.402 -35.20823.949 1.00 38.10 C

ATOM2332 CD GLU B 94 -15.564 -33.72323.717 1.00 40.05 C

ATOM2333 OE1GLU B 94 -19.628 -32.96024.046 1.00 42.80 0 ATOM2334 OE2GLU B 94 -16.629 -33.31523.214 1.00 45.22 0 ATOM2335 N ALA B 95 -13.733 -38.04724.026 1.00 26.43 N

ATOM2336 CA ALA B 95 -12.515 -38.60023.426 1.00 25.55 C

ATC)M2337 C ALA B 95 -12.306 -37.97422.052 1.00 25.77 C

ATOM2338 0 ALA B 95 -13.257 -37.81921.281 1,00 25.94 O

ATOM2339 CB ALA B 95 -12.611 -40.11823.293 1.00 24.19 C

ATOM2340 N ARG B 96 -11.061 -:37.62021.748 1.00 25.00 N

ATc>M2341 CA ARG B 96 -10.720 -37.00420.470 1.00 25.36 C

ATOM2342 C ARG B 96 -9.410 -37.54319.900 1.00 25.14 C

ATOM2343 0 ARG B 96 -8.531 -37.97320.649 1.00 25.39 0 ATOM2344 CB ARG B 96 -10.586 -35.48920.635 1.00 27.26 C

ATOM2345 CG ARG B 96 -11.882 -34.74720.915 1.00 26.14 C

ATOM2346 CD ARG B 96 -11.614 -33.25921.145 1.00 27.80 C

ATOM2347 NE ARG B 96 -12.833 -32.52021.472 1.00 30.37 N

ATOM2348 CZ ARG B 96 -13.351 -31.55120.717 1.00 32.25 C

ATOM2349 NH1ARG B 96 -12.?56 -31.19119.587 1.00 33.36 N

ATOM2350 NH2ARG B 96 -14.473 -30.94421.087 1.00 33.46 N

ATOM2351 N TYR B 97 -9.286 -37.52418.574 1.00 24.02 N

ATOM2352 CA TYR B 97 -8.059 -37.97217.918 1.00 22.38 C

ATOM2353 C TYR B 97 -7.088 -36.79417.889 1.00 23.83 C

ATOM2354 0 TYR B 97 -7.439 -35.72617.389 1.00 24.07 0 ATOM 2355 CB TYRB 97 -8.319 -38.37916.467 1.0022.26 C

ATOM 2356 CG TYRB 97 -9.171 -39.61216.275 1.0021.26 C

ATOM 2357 CD1 TYRB 97 -10.357 -39.54915.553 1.0021.79 C

ATOM 2358 CD2 TYRB 97 -8.765 -40.84816.770 1.0022.13 C

ATGM 2359 CE1 TYRB 97 -11.123 -40.68315.319 1.0021.53 C

ATOM 2360 CE2 TYRB 97 -9.524 -41.99516.540 1.0023.60 C

ATOM 2361 CZ TYRB 97 -10.697 -41.90215.812 1.0023.21 C

ATOM 2362 OH TYRB 97 -11.431 -93.03015.544 1.0022.39 0 ATOM 2363 N HISB 98 -5.871 -36.96718.405 1.0023.85 N

ATOM 2364 CA HISB 98 -4.924 -35.86118.353 1.0023.63 C

ATOM 2365 C HISB 98 -4.134 -35.86617.049 1.0025.81 C

ATOM 2366 0 HISB 98 -3.396 -34.91516.757 1.0024.96 0 ATcJM2367 CB HISB 98 -3.984 -35.87919.566 1.0023.63 C

ATOM 2368 CG HISB 98 -3.042 -37.04719.612 1.0024.30 C

ATOM 2369 ND1 HISB 98 -2.018 -:37.21818.706 1.0022.68 N

ATOM 2370 CD2 HISB 98 -2.946 -:38.07820.486 1.0022.60 C

ATOM 2371 CE1 HISB 98 -1.330 -38.30119.020 1.0022.35 C

ATOM 2372 NE2 HISB 98 -1.873 -38.84220.097 1.0022.57 N

ATOM 2373 N ASPB 99 -4.313 -36.91316.241 1.0024.87 N

ATOM 2374 CA ASPB 99 -3.592 -37.00714.976 1.0024.94 C

ATOM 2375 C ASPB 99 -4.495 -36.99213.705 1.0025,63 C

ATOM 2376 0 ASPB 99 -3.972 -37.40112.696 1.0027.33 0 ATOM 2377 CB ASPB 99 -2.696 -38.25314.972 1.0024.17 C

ATOM 2378 CG ASPB 99 -3.479 -39.54915.101 1.0024.48 C

ATOM 2379 OD1 ASPB 99 --4.712 -39.50415.312 1.0023.54 0 A"'OM2380 OD2 ASPB 99 -2.846 -40.62315.002 1.0025.43 0 A'.COM2381 N ALAB 100 -5.691 -36.53013.797 1.0025.12 N

ATOM 2382 CA ALAB 100 -6.558 -36.46212.617 1.0024.78 C

A'rOM2383 C ALAB 100 -6.592 --35.00712.183 1.0025.30 C

ATOM 2384 0 ALAB 100 -6.742 --34.11613.016 1.0023.68 0 A~rOM2385 CB ALAB 100 -7.967 -36.94412.947 1.0022.85 C

ATOM 2386 N ASPB 101 -6.454 -34.76710.884 1.0027.23 N

ATOM 2387 CA ASPB 101 -6.431 -33.39910.386 1.0029.26 C

ATOM 2388 C ASPB 101 -7.047 -33.2299.004 1.0029.11 C

ATOM 2389 O ASPB 101 -6.459 -33.6197.989 1,0028.29 0 ATOM 2390 CB ASPB 101 -4.979 -32.89210.385 1.0030.14 C

P,TOM2391 CG ASPB 101 -4.853 -31.4409.944 1.0032.87 C

F,TOM2392 OD1 ASPB 101 -3.723 -30.90510.014 1.0034.38 O

ATOM 2393 OD2 ASPB 101 -5.864 -30.8339.527 1.00 31.31 0 ATOM 2394 N VALB 102 -8.247 -32.6558.981 1.00 28.46 N

ATOM 2395 CA VALB 102 -8.950 -32.3757.739 1.00 28.68 C

ATOM 2396 C VALB 102 -9.428 -30.9337.886 1.00 29.36 C

ATOM 2397 0 VALB 102 -10.482 -30.5467.384 1.00 27.89 O

ATOM 2398 CB VALB 102 -10.160 -33.3247.528 1.00 29.52 C

ATOM 2399 CG1 VALB 102 -10.760 -33.1056.143 1.00 29.54 C

ATOM 2400 CG2 VALB 102 -9.715 -34.7657.657 1.00 31.15 C

ATOM 2401 N THRB 103 -8.624 -30.1388.585 1.00 29.29 N

ATOM 2402 CA THRB 103 -8.946 -28.7388.815 1.00 32.68 C

ATOM 2403 C THRB 103 -9.050 -27.9687.506 1.00 33.70 C

ATOM 2404 0 THRB 103 -9.672 -26.9097.453 1.00 33.77 O

ATOM 2405 CB THR8 103 -7.886 -28.0649.698 1.00 31.68 C

ATOM 2406 OGl THRB 103 -6.596 -28.2139.094 1.00 34.04 O

ATOM 2407 CG2 THRB 103 -7.880 -28.69411.0791.00 32.71 C

ATOM 2408 N ALAB 104 -8.446 -28.5056.452 1.00 34.78 N

ATOM 2409 CA ALAB 104 -8.485 -27.8555.148 1.00 37.01 C

ATC)M2410 C ALAB 104 -9.930 -27.6984.661 1.00 37.17 C

ATOM 2411 0 ALAB 104 -10.219 -26.8483.819 1.00 38.28 O

ATOM 2412 CB ALAB 104 -7.668 -28.6634.131 1.00 37.48 C

ATOM 2413 N PHEB 105 -10.832 -28.5155.200 1.00 36.29 N

ATOM 2414 CA PHEB 105 -12.237 -28.4664.812 1.00 34.18 C

ATOM 2415 C PHEB 105 -1:3.196 -28.0565.924 1.00 31.93 C

ATOM 2916 O PHEB 105 -14.353 -28.4805.950 1.00 31.04 0 ATOM 2417 CB PHEB 105 -12.650 -29.8124.211 1.00 36.16 C

ATOM 2418 CG PHEB 105 -12.134 -30.0182.818 1.00 38.48 C

ATOM 2419 CD1 PHEB 105 -12.746 -29.3891.739 1.00 39.77 C

ATOM 2420 CD2 PHEB 105 -10.986 -30.7722.590 1.00 39.37 C

ATOM 2421 CE1 PHEB 105 -12.219 -29.4920.455 1.00 40.91 C

ATOM 2422 CE2 PHEB 105 -10.448 -30.8861.309 1.00 39.90 C

ATOM 2423 CZ PHEB 105 -11.065 -30.2440.240 1.00 39.98 C

ATOM 2424 N GLYB 106 -X2.703 -27.2336.846 1.00 30.91 N

ATOM 2425 CA GLYB 106 -13.537 -26.7327.928 1.00 29.18 C

ATOM 2426 C GLYB 106 -13.740 -27.6059.147 1.00 29.57 C

ATOM 2427 0 GLYB 106 -14.508 -27.24810.0401.00 28.69 0 ATOM 2428 N TYRB 107 -13.078 -28.7579.187 1.00 28.66 N

A~'OM2429 CA TYRB 107 -13.196 -29.66010.3321.00 28.85 C

ATOM 2430 C TYRB 107 -:L2.361 -29.14511.5001.00 29.67 C

ATOM2431 O TYR B107 -11.289 -28.57611.292 1.0031.54 O

ATOM2432 CB TYR B107 -12.711 -31.0649.943 1.0025.16 C

ATOM2433 CG TYR B107 -13.685 -31.7969.058 1.0024.42 C

ATOM2434 CD1 TYR B107 -14.790 -32.4539.601 1.0023.80 C

ATOM2435 CD2 TYR B107 -13.556 -31.7607.669 1.0023.11 C

ATOM2436 CE1 TYR B107 -15.739 -33.0448.783 1.0023.04 C

ATOM2437 CE2 TYR B107 -14.500 -32.3516.846 1.0023,65 C

ATOM2438 CZ TYR B107 -15.586 -32.9867.410 1.0022.12 C

ATOM2439 OH TYR B107 -16.529 -33.5546.596 1.0023.05 0 ATOM2440 N GLU B108 -12.853 -29.31812.724 1.0030.35 N

ATOM2441 CA GLU B108 -12.071 -28.89213.879 1.0031.64 C

ATOM2442 C GLU B108 -10.878 -29.82813.855 1.0030.66 C

ATtJM2443 O GLU B108 -10.973 -30.93413.315 1.0027.55 O

ATOM2444 CB GLU B108 -12.805 -:?9.12715.197 1.0033.42 C

ATOM2445 CG GLU B108 -14.134 -28.44315.348 1.0039.20 C

ATOM2446 CD GLU B108 -14.634 -28.54016.769 1.0041.01 C

ATOM2447 OE1 GLU B108 -15.849 -28.37216.987 1.0044.84 0 ATOM2448 OE2 GLU B108 -13.797 -28.77817.670 1.0043.11 O

ATOM2449 N TYR B109 -9.761 -29.40514.434 1.0029.64 N

ATOM2450 CA TYR B109 -8.595 -30.27214.451 1.0030.13 C

ATOM2451 C TYR B109 -8.994 -31.53315.214 1.0028.55 C

ATOM2452 O TYR B109 -9.698 -31.45716.226 1.0028.20 0 ATOM2453 CB TYR B109 -7.407 -29.59715.140 1.0031.53 C

ATOM2454 CG TYR B109 -6.132 -30.38414.948 1.0033.47 C

A7.'OM2455 CD1 TYR B109 -5.368 -30.23713.792 1.0033.73 C

ATOM2456 CD2 TYR B109 --5.751 -31.36015.868 1.0034.68 C

A'COM2457 CE1 TYR B109 -4.261 -31.04813.549 1.0036.18 C

A'POM2458 CE2 TYR B109 -4.645 --32.18015.632 1.0036.80 C

ATOM2459 CZ TYR B109 -3.909 --32.02014.471 1.0037.30 C

ATOM2460 OH TYR B109 -2.839 -32.84814.220 1.0039.41 0 ATOM2461 N GLY B110 -8.559 -32.68914.721 1.0027.63 N

ATOM2462 CA GLY B110 -8.898 -33.94615.373 1.0025.29 C

ATOM2463 C GLY B110 -10.226 -34.54314.933 1.0025.30 C

ATOM2464 O GLY B110 -10.513 -35.69915.237 1.0025.69 0 ATOM2465 N GLN B111 -11.047 -33.76814.225 1.0023.74 N

P,TOM2466 CA GLN B111 -12.344 -34.26113.762 1.0024.53 C

P.TOM2467 C GLN B111 -12.249 -34.86812.365 1.0024.31 C

ATOM2468 0 GLN B111 -11.591 -34.31511.479 1.0026.04 O

ATOM 2469 CB GLNB 111 -13.376 -33.11913.754 1.0024.53 C

ATOM 2470 CG GLNB 111 -14.730 -33.49313.151 1.0025.68 C

ATOa~2471 CD GLNB 111 -15.727 -32.33913.175 1.0027.76 C

ATOM 2472 OE1 GLNB 111 -15.338 -31.16513.164 1.0026.99 O

ATOM 2473 NE2 GLNB 111 -17.018 -32.67013.183 1.0024.38 N

ATOM 2474 N LEUB 112 -12.896 -36.00912.168 1.0025.17 N

ATOM 2475 CA LEUB 112 -12.879 -36.66910.870 1.0026.54 C

ATOM 2476 C LEUB 112 -14.239 -36.56910.201 1.0026.77 C

ATOM 2477 O LEUB 112 -15.257 -36.42010.871 1.0025.65 0 ATGM 2478 CB LEUB 112 -12.505 -38.14511.018 1.0024.64 C

ATOM 2479 CG LEUB 112 -11.043 -38.46711.335 1.0026.45 C

ATC>M2480 CD1 LEUB 112 -10.907 -39.95611.568 1.0025.15 C

ATOM 2481 CD2 LEUB 112 -10.143 -38.03510.190 1.0025.49 C

ATOM 24$2 N PROB 113 -14.269 -36.6338.861 1.0027.82 N

ATOM 2483 CA PROB 113 -15.538 -36.5528.134 1.0027.50 C

ATOM 2484 C PROH 113 -16.455 -37.6508.645 1.0028.11 C

ATOM 2485 0 PROB 113 -15.993 -38.7478.960 1.0027.89 0 ATOM 2486 CB PROB 113 -15.116 -36.7786.689 1.0028.18 C

ATOM 2487 CG PROB 113 -13.752 -36.1316.693 1.0026.55 C

ATOM 2488 CD PROB 113 -13.125 -36.6397.929 1.0026.65 C

ATOM 2489 N GLYB 114 -17.745 -37.3448.751 1.0028.38 N

ATOM 2490 CA GLYB 114 -18.710 -38.3199.225 1.0027.23 C

ATOM 2491 C GLYB 114 -18.803 -38.45410.731 1.0028.20 C

ATOM 2492 0 GLYB 114 -19.623 -39.21711.225 1.0029.80 0 ATOM 2493 N CYSB 115 -17.987 -37.71011.475 1.0027.13 N

ATOM 2494 CA CYSB 115 -18.005 -37.80912.932 1.0026.27 C

ATOM 2495 C CYSB 115 -18.117 -36.45813.611 1.0025.86 C

ATOM 2496 0 CYSB 115 ?7.853 -35.42913.006 1.0025.92 O

ATOM 2497 CB CYSB 115 -16.703 -38.43313.447 1.0028.12 C

ATOM 2498 SG CYSB 115 -16.054 -39.80312.493 1.0027.23 S

A~roM2499 N PROB 116 -18.509 -36.45214.893 1.0027.11 N

A'rOM2500 CA PROB 116 -18.622 -35.20115.646 1.0027.05 C

ATOM 2501 C PROB 116 -17.166 -34.$7516.018 1.0028.39 C

ATOM 2502 O PROB 116 -16.296 -35.74515.894 1.0027.38 0 ATOM 2503 CB PROB 116 -19.469 -35.60016.845 1.0026.52 C

ATOM 2504 CG PROB 116 -19.046 -37.04317.077 1.0028.42 C

ATOM 2505 CD PROB 116 -19.016 -37.59715.673 1.0025.80 C

F,TOM2506 N ALAB 117 -16.887 -33.64916.458 1.0027.40 N

ATOM 2507 CA ALA B 117 -15,514 -3,1.27116.7951.00 27.81 C

ATOM 2508 C ALA B 117 -14.906 -34.21217.8361.00 28.33 C

ATOM 2509 O ALA B 117 -13.714 -34.53017.7981.00 28.87 0 ATOM 2510 CB ALA B 117 -15.478 -31.82917.2971.00 29.86 C

ATOM 2511 N GLY B 118 -15.740 -34.65418.7621.00 28.00 N

ATOM 2512 CA GLY B 118 -15.294 -35.56119.7961.00 26.94 C

ATOM 2513 C GLY B 118 -16.432 -36.49820.1331.00 27.70 C

ATOM 2514 0 GLY B 118 -17.601 -36.19519.8761.00 29.39 0 ATOM 2515 N PHE B 119 -16.096 -3'7.63320.7241.00 26.54 N

ATOM 2516 CA PHE B 119 -17.087 -38.62721.0961.00 28.22 C

ATOM 2517 C PHE B 119 -17.367 -38.53722.5911.00 28.86 C

ATOM 2518 0 PHE B 119 -16.463 -38.70723.4141.00 29.15 0 ATOM 2519 CB PHE B 119 -16.562 -40.00720.7121.00 26.67 C

ATOM 2520 CG PHE B 119 -16.162 -40.10319.2661.00 26.61 C

ATOM 2521 CD1PHE B 219 -17.117 -40.30318.2781.00 27.23 C

ATOM 2522 CD2PHE B I19 -14.837 -39.93918.8901.00 25.39 C

ATOM 2523 CE1PHE B I19 -16.756 -40.33716.9351.00 28.29 C

ATC>M2524 CE2PHE B 119 -14.463 -39.97117.5521.00 26.15 C

ATOM 2525 CZ PHE B 119 -15.427 -90.17116.5701.00 27.86 C

ATOM 2526 N LYS B 120 -18.625 -38.27322.9321.00 28.44 N

ATOM 2527 CA LYS B 120 -19.037 -38.12624.3201.00 29.67 C

ATOM 2528 C LYS B 120 -19.377 -39.42025.0481.00 28.12 C

ATOM 2529 O LYS B 120 -20.196 -40.21824.5811.00 28.29 0 ATOM 2530 CB LYS B 120 -20.237 -37.17824.4011.00 33.26 C

ATOM 2531 CG LYS B I20 -19.966 -35.80223.7941.00 39.71 C

ATOM 2532 CD LYS B 120 -21.149 -34.85823.9801.00 42.62 C

ATOM 2533 CE LYS B 120 -20.904 -33.51823.2951.00 45.07 C

ATOM 2534 NZ LYS B 120 -19.619 -32.89623.7131.00 46.06 N

ATOM 2535 N ALA B 121 -18.736 -39.62326.1951.00 25.93 N

ATOM 2536 CA ALA B 121 -19.001 -40.78627.0251.00 26.54 C

ATOM 2537 C ALA B 121 -20.371 -40.52827.6411.00 28.33 C

ATOM 2538 0 ALA B 121 -20.806 -39.37527.7461.00 26.02 0 ATOM 2539 CB ALA B 121 -17.953 -40.91728.1131.00 25.74 C

ATOM 2540 N ASP B 122 -21.052 -41.59428.0431.00 28.04 N

ATOM 2541 CA ASP B 122 -22.379 -41.46628.6201.00 30.85 C

ATOM 2542 C ASP B 122 -22.352 -40.81430.0001.00 31.92 C

ATOM 2543 0 ASP B 122 -21.615 -41.25430.8901.00 29.97 0 ATOM 2544 CB ASP B 122 -23.040 -42.84228.7211.00 32.68 C

AT0192545 CG ASPB 122 -24.4?1 -42..76229.2071.00 34.03 C

ATOM 2546 OD1 ASPB 122 -25.341 -42.32128.4241.00 33.99 0 ATOM 2547 OD2 ASPB 122 -24.720 -43.13230.3741.00 34.23 0 ATOLM2548 N ASPB 123 -23.168 -39.77230.1621.00 32.79 N

ATOM 2549 CA ASPB 123 -23.276 -3!x.03231.9221.00 34.42 C

ATOM 2550 C ASPB 123 -23.491 -39.96532.6031.00 33.98 C

ATOM 2551 O ASPB 123 -22.803 -39.86533.6201.00 34.13 0 ATOM 2552 CB ASPB 123 -24.450 -38.05431.3731.00 35.68 C

ATOM 2553 CG ASPB 123 -24.199 -36.87630.4651.00 38.43 C

ATOM 2554 OD1 ASPB 123 -25.167 -36.43129.8091.00 41.46 0 ATOM 2555 OD2 ASPB 123 -23.053 -36.38230.4161.00 39.31 0 ATOM 2556 N LYSB 124 -24.456 -40.86832.4701.00 34.06 N

ATOM 2557 CA LYSB 124 -24.758 -41.79633.5491.00 35.13 C

ATOM 2558 C LYSB 124 -23.611 -42.74733.8341.00 33.98 C

ATOM 2559 0 LYSB 124 -23.326 -43.09634.9921.00 34.42 0 ATOM 2560 CB LYSB 124 -26.021 -42.59933.2371.00 37.12 C

ATOM 2561 CG LYSB 124 -21.2?0 -41.75133.0821.00 42.17 C

ATOM 2562 CD LYSB 124 -28.500 -92.62332.8561.00 45.05 C

ATOM 2563 CE LYSB 124 -29.717 -41.77032.5361.00 48.89 C

ATOM 2564 NZ LYSB 124 -29.495 -40.95231.3071.00 51.05 N

ATOM 2565 N LEUB 125 -22.953 -43.22632.7831.00 33.27 N

ATOM 2566 CA LEUB 125 -21.836 -X14.14532.9561.00 31.47 C

ATOM 2567 C LEUB 125 -20.656 -43.43933.6121.00 31.16 C

ATOM 2568 0 LEUB 125 -19.955 -44.02534.4391.00 30.96 O

ATOM 2569 CB LEUB 125 -21.411 -44.73631.6061.00 30.32 C

ATOM 2570 CG LEUB 125 -22.391 -45.70630.9331.00 30.87 C

ATOM 2571 CD1 LEUB 125 -21.832 -46.15229.5901.00 26.09 C

ATOM 2572 CD2 LEUB 125 -22.625 -46.91731.8391.00 31.76 C

ATOM 2573 N ILEB 126 -20.434 -42.18333.2361.00 30.97 N

ATOM 2574 CA ILEB 126 -19.344 -41.40133.8121.00 31.12 C

ATOM 2575 C ILEB 126 -19.530 -41.28735.3251.00 31.93 C

ATOM 2576 0 ILEB 126 -18.642 -41.63936.0991.00 33.12 0 ATOM 2577 CB ILEB 126 -19.299 -39.97933.2101.00 30.48 C

ATOM 2578 CG1 ILEB 126 -18.879 -40.05131.7401.00 29.91 C

ATOM 2579 CG2 ILEB 126 -1.8.348 -39.09934.0131.00 31.73 C

ATOM 2580 CD1 ILEB 126 -19.050 -38.74230.9911,00 30.77 C

ATOM 2581 N ALAB 127 -20.691 -40.79435.7401.00 32.32 N

ATOM 2582 CA ALAB 127 -20.987 -40.63437.1581.00 32.96 C

ATOM 2583 C ALAB 127 -20.814 -41.95137.9201.00 33.20 C

ATOM 2584 O ALAB 127 -20.276 -41.97139.0301.00 32.02 0 ATOM 2585 CB ALAB 127 -22.411 -40.09937.3381.00 31.62 C

ATOM 2586 N ALAB 128 -21.263 -93.05137.3221.00 33.19 N

ATOM 2587 CA ALAB 128 -21.154 -49.35937.9601.00 32.14 C

ATOM 2588 C ALAB 128 -3.9.694-44.77438.1321.00 32.60 C

ATOM 2589 0 ALAB 128 -19.306 -45.31639.1691.00 32.83 0 ATOM 2590 CB ALAB 128 -21.903 -45.40637.1381.00 33.46 C

ATOM 2591 N ALAB 129 -18.886 -44.52737.1101.00 32.62 N

ATOM 2592 CA ALAB 129 -17.474 -44.87837.1731.00 32.47 C

ATGM 2593 C ALAB 129 -16.813 -44.03138.2601.00 32.55 C

ATOM 2594 0 ALAB 129 -15.991 -44.51439.0291.00 31.00 0 ATOM 2595 CB ALAB 129 -16.804 -44.62435.8191.00 30.25 C

ATOM 2596 N GLUB 130 -17.187 -42.76238.3281.00 31.91 N

ATOM 2597 CA GLUB 130 -16.611 -91.88139.3291.00 33.11 C

ATOM 2598 C GLUB 130 -16.927 -9:2.35940.7401.00 33.06 C

ATOM 2599 0 GLUB 130 -16.064 -42.31741,6161.00 33.06 0 ATOM 2600 CB GLUB 130 -17.101 -90.44639.1081.00 33,23 C

ATOM 2601 CG GLUB 130 -16.242 -39.68438.1101.00 35.53 C

ATOM 2602 CD GLUB 130 -16.892 -38.91237.6211.00 38.16 C

ATOM 2603 OE1 GLUB 130 -16.198 -37.61136.9621.00 39.53 0 ATOM 2604 OE2 GLUB 130 -18.100 -:38.21937.8831.00 38.24 0 ATOM 2605 N ALAB 131 -18.151 -92.83590.9541.00 32.07 N

ATOM 2606 CA ALAB 131 -18.556 -43.32442.2681.00 33.16 C

ATOM 2607 C ALAB 131 -17.774 -44.57842.6551.00 33.00 C

ATOM 2608 0 ALAB 131 -17.350 -44.73343.8031.00 31.22 0 ATOM 2609 CB ALAB 131 -20.065 -43.62042.2831.00 33.42 C

ATOM 2610 N CYSB 132 -17.588 -45.47541.6951.00 32.95 N

ATOM 2611 (:A CYSB 132 -16.857 -46.71541.9511.00 32.35 C

ATOM 2612 C CYSB 132 -15.404 -46.44042.3161.00 31.22 C

ATOM 2613 O CYSB 132 -14.850 -47.05543,2291.00 30.56 O

ATOM 2619 CB CYSB 132 -16.921 -47.62190.7211.00 33.24 C

ATOM 2615 SG CYSB 132 -18.578 -48.26040.4081.00 36.60 S

ATOM 2616 N ILEB 133 -14.787 -45.50341.6081.00 30.87 N

ATOM 2617 CA ILEB 133 -13.398 -45.16041.8811.00 30.65 C

ATOM 2618 C ILEB 133 -13.253 -44.55443.2871.00 31.08 C

A'.COM2619 0 ILEB 133 -12.351 -94.92344.0381.00 29.61 O

A'COM2620 CB ILEB 133 -12.876 --44.19140.8051.00 31.34 C

ATOM 2621 CG1 ILEB 133 -12.901 -44.90639.4481.00 29.74 C

ATOM 2622 CG2 ILEB 133 -11.471 -43.71141.1591.00 29.08 C

ATO1H2623 CD1 TLEB 133 -12.761 -43.99138.2431.00 30.35 C

AT01H2624 N ALAB 134 -14.157 -4:3.64543.6451.00 32.09 N

ATOM 2625 CA ALAB 134 -14.129 -43.01344.9651.00 33.56 C

ATOM 2626 C ALAB 134 -14.293 -44.07346.0551.00 34.88 C

ATOM 2627 0 ALAB 134 -13.577 -44.06947.0621.00 34.40 0 ATOM 2628 CB ALAB 134 -15.242 -41.98445.0721.00 32.89 C

ATOM 2629 N GLUB 135 -15.234 -44.98645.8451.00 34.62 N

ATOM 2630 CA GLUB 135 -15.492 -46.05946.7991.00 35.98 C

ATOM 2631 C GLUB 135 -14.270 -46.94047.0901.00 35.22 C

ATOM 2632 0 GLUB 135 -14.190 -47.64148.0511.00 35.88 0 ATOM 2633 CB GLUB 135 -16.646 -46.92646.3041.00 36.92 C

ATOM 2634 CG GLUB 135 -17.994 -46.24946.3821.00 41.85 C

ATOM 2635 CD GLUB 135 -19.074 -47.05545.6991.00 43.75 C

ATOM 2636 OE1 GLUB 135 -18.837 -48.25445.4231.00 44.84 0 ATOM 2637 OE2 GLUB 135 -20.158 -46.49145.4451.00 45.18 0 ATOM 2638 N LEUB 136 -13.328 -96.91146.1051.00 34.51 N

ATOM 2639 CA LEUB 136 -12.106 -97.70346.2121.00 33.13 C

ATOM 2640 C LEUB 136 -10.959 -46.87746.8021.00 32.45 C

ATOM 2641 0 LEUB 136 -9.817 -47.33546.8671.00 30.62 O

ATOM 2642 CB LEUB 136 -11.700 -48.22644.8301.00 34.12 C

ATOM 2643 CG LEUB 136 -12.641 -49.24344.1801.00 35.70 C

ATOM 2644 CD1 LEUB 136 -12.156 -49.56442.7671.00 36.10 C

ATOM 2645 CD2 LEUB 136 -12.684 -50.51045.0301.00 37.41 C

ATOM 2646 N ASNB 137 -11.267 -45.65547.2211.00 31.96 N

ATOM 2647 CA ASNB 137 -10.264 -44.76947.8071.00 32.25 C

ATOM 2648 C ASNB 137 -9.200 -44.33346.7971.00 33.13 C

ATOM 2649 0 ASNB 137 -8.055 -44.04047.1651.00 31.84 0 ATOM 2650 CB ASNB 137 -9.600 -45.45948.9981.00 31.99 C

ATOM 2651 CG ASNB 137 -10.602 -45.87350.0561.00 33.30 C

ATOM 2652 OD1 ASNB 137 -10.591 -47.01350.5281.00 30.31 0 ATOM 2653 ND2 ASNB 137 -11.476 -44.94850.4351.00 30.19 N

ATOM 2654 N LEUB 138 -9.584 -44.28745.5291.00 33.01 N

ATOM 2655 CA LEUB 138 -8.670 -43.87944.4681.00 32.89 C

ATOM 2656 C LEUB 138 -9.127 -42.52643.9641.00 33.03 C

ATOM 2657 O LEUB 138 -10.243 -42.10744.2511.00 32.78 0 A~OM 2658 CB LEUB 138 -8.682 -44.90743.3411.00 34.22 C

ATOM 2659 CG LEUB138 -8.202 -46.29143.7911.00 34.87 C

ATO1~2660 CD1 LEUB138 -8.437 -4'1.29442.6911.00 37.04 C

ATOM 2661 CD2 LEUB138 -6.730 -46.23144.1601.00 35.75 C

ATOM 2662 N ASNB139 -8.277 -41.83343.2191.00 33.78 N

ATOM 2663 CA ASNB139 -8.658 -40.51942.7351.00 36.42 C

ATOM 2664 C ASNB139 -9.043 -40.48141.2691.00 35.86 C

ATOM 2665 0 ASNB139 -8.248 -40.82040.3971.00 35.63 0 ATOM 2666 CB ASNB139 -7.542 -39.50742.9911.00 37.25 C

ATOM 2667 CG ASNB139 -7.997 -38.08542.7431.00 40.64 C

ATOM 2668 OD1 ASNB139 -9.086 -37.69343.1721.00 42.53 0 ATOM 2669 ND2 ASNB139 -7.172 -37.30142.0561.00 40.84 N

ATOM 2670 N ALAB140 -10.270 -40.04841.0071.00 36.17 N

ATOM 2671 CA ALAB140 -10.767 -39.96639.6461.00 35.98 C

ATOM 2672 C ALAB140 -10.726 -38.52639.1771.00 35.66 C

ATOM 2673 0 ALABI40 -11.066 -37.61139.9271.00 35.93 0 ATOM 2674 CB ALAB140 -12.195 -40.49939.5741.00 36.97 C

ATOM 2675 N VALB141 -10.302 -38.33237.9331.00 33.52 N

ATOM 2676 CA VALB141 -10.231 -37.00537.3381.00 32.16 C

ATOM 2677 C VALB141 -10.999 -3.7.06936.0221.00 31.71 C

ATOM 2678 O VALB141 -10.716 -37.91535.1811.00 30.60 0 ATUM 2679 CB VALB141 -8.764 -36.59937.0691.00 31.16 C

ATOM 2680 CG1 VALB141 '8.709 -35.19536.4821.00 31.38 C

ATOM 2681 CG2 VALB141 -7.962 -36.66938.3491.00 32.79 C

ATOM 2682 N ARGB142 -11.976 -36.18835.8471.00 32.22 N

ATOM 2683 CA ARGB142 -12.770 -36.19134.6221.00 32.75 C

ATOM 2684 C ARGB142 -12.216 -35.20133.6161.00 31.68 C

ATOM 2685 0 ARGB142 -11.854 -:34.08133.9741.00 32.50 0 ATOM 2686 CB ARGB142 -14.229 -35.84034.9251.00 34.44 C

ATOM 2687 CG ARGB142 -15.135 -35.96733.7121.00 37.16 C

ATOM 2688 CD ARGB142 -16.508 -35.36033.9381.00 38.77 C

ATOM 2689 NE ARGB142 -17.188 -35.90835.1081.00 38.11 N

ATOM 2690 CZ ARGB142 -18.460 -35.65935.4021.00 39.50 C

ATOM 2691 NH1 ARGB142 -19.179 -34.87834.6061.00 39.24 N

ATOM 2692 NH2 ARGB142 -19.013 -36.18136.4891.00 38.40 N

ATOM 2693 N GLYB143 -12.147 -35.61232.3541.00 30.26 N

ATOM 2694 CA GLYB143 -1.1.644 -34.71531.3311.00 30.03 C

ATOM 2695 C GLYB143 -1.1.503 -35.33729.9601.00 28.67 C

ATOM 2696 O GLYB193 -11.896 -36.48129.7321.00 29.67 0 ATOM 2697 N LEUB 144 -10.941 -34.56629.0381.00 28.10 N

ATOM 2698 CA LEUB 144 -10.724 -35.01327.6701.00 27.16 C

ATO?H2699 C LEUB 144 -9.492 -35.90627.5171.00 26.83 C

ATOM 2700 0 LEUB 144 -8.411 -35.57928.0051.00 24.86 O

ATOM 2701 CB LEUB 144 -10.564 -33.80326.7461.00 25.01 C

ATOM 2702 CG LEUB 144 -10.064 -34.07725.3211.00 26.78 C

ATOM 2703 CD1 LEUB 144 -11.098 -34.91324.5451.00 25.71 C

ATOM 2704 CD2 LEUB 144 -9.808 -32.75524.6111.00 26.46 C

ATOM 2705 N ILEB 145 -9.671 -37.03126.8331.00 27.77 N

ATOM 2706 CA ILEB 145 -8.577 -37.96426.5471.00 28.14 C

ATOM 2707 C ILEB 145 -8.367 -37.92225.0301.00 26.68 C

ATOM 2708 O ILEB 145 -9.336 -37.95624.2711.00 27.05 0 ATOM 2709 CB ILEB 145 -8.928 -39.42826.9281.00 28.69 C

ATOM 2710 CG1 ILEB 145 -9.084 -39.57328.4441.00 32.36 C

ATC>M2711 CG2 ILEB 145 -;'.805 -40.36526.4681.00 29.53 C

ATOM 2712 CD1 ILEB 145 -10.215 -38.76329.0381.00 36.13 C

ATOM 2713 N VALB 146 -7.119 -37.82324.5841.00 24.43 N

ATOM 2714 CA VALB 146 -6.840 -37.80723.1541.00 23.64 C

ATOM 2715 C VALB 146 -6.061 -39.07022.7971.00 24.84 C

ATOM 2716 0 VALB 146 -5.321 -39.60023.6341.00 25.69 0 ATOM 2717 CB VALB 146 -6.038 -36.53422.7281.00 23.20 C

ATOM 2718 CG1 VALB 146 -6.909 -35.28122.9281.00 21.56 C

ATOM 2719 CG2 VALB 146 -4.745 -36.41723.5331.00 23.96 C

ATOM 2720 N SERB 147 -6.246 -:39.55621.5701.00 23.07 N

ATOM 2721 CA SERB 147 -5.574 -40.77421.0981.00 24.56 C

ATOM 2722 C SERB 147 -4.981 -40.56419.7251.00 22.28 C

ATOM 2723 0 SERB 147 -5.441 -39.71418.9681.00 24.47 0 ATOM 2724 CB SERB 147 -6.553 -41.94720.9681.00 23.98 C

ATOM 2725 OG SERB 147 -7.287 -42.16622.1471.00 31.19 0 ATOM 2726 N GLYB 148 -3.988 -41.38119.3951.00 21.14 N

ATOM 2727 CA GLYB 148 -3.347 -41.29518.0981.00 22.07 C

ATOM 2728 C GLYB 198 -2.449 -42.50117.9631.00 21.24 C

ATOM 2729 O GLYB 148 -2.181 -43.16118.9631.00 23.75 0 ATOM 2730 N ASPB 149 -1.991 -42.79916.7501.00 22.46 N

ATOM 2731 CA ASPB 149 -1.115 -43.95116.5351.00 24.47 C

A'.~OM2732 C ASPB 149 0.366 -43.65816.7701.00 26.75 C

A'COM2733 0 ASPB 149 1.225 --44.02715.9761.00 24.87 0 A'rOM2734 CB ASPB 149 -1.318 -44.51515.1271.00 23.06 C

ATOM 2735 CG ASPB 149 -2.496 -4.5.47215.0611.00 24.54 C

ATOM 2736 OD1 ASPB 149 -2.939 -45.91716.1391.00 24.89 0 ATOM 2737 OD2 ASPB 149 -2.967 -45.79413.9471.00 24.54 0 ATOM 2738 N ALAB 150 0.662 -43.00$17.8861.00 29.49 N

ATOM 2739 CA ALAB 150 2.039 -42.67618.2041.00 32.48 C

ATOM 2740 C ALAB 150 2.219 -42.59419.7051.00 34.97 C

ATOM 2741 0 ALAB 150 1.277 -42.27520.4421.00 34.34 0 ATOM 2742 CB ALAB 150 2.425 -41.33717.5591.00 29.50 C

ATOM 2743 N PHEB 151 3.429 -42.91320.1531.00 35.88 N

ATOM 2744 CA PHEB 151 3.763 -92.83021.5611.00 38.57 C

ATOM 2745 C PHEB 151 4.320 -91.42621.7291.00 39.77 C

ATOM 2746 0 PHEB 151 5.229 -41.02821.0021.00 40.25 O

ATOM 2747 CB PHEB 151 4.843 -43.84021.9371.00 41.33 C

ATOM 2748 CG PHEB 151 5.222 -43.78723.3871.00 44.10 C

ATOM 2749 CD1 PHEB 151 4.415 -44.38524.3501.00 45.70 C

ATOM 2750 CD2 PHEH 151 6.349 -43.08623.7971.00 44.98 C

ATOM 2751 CE1 PHEB 151 4.725 -44.28225.7061.00 47.09 C

ATOM 2752 CE2 PHEB 152 6.668 -42.97425.1471.00 46.88 C

ATOM 2753 CZ PHEB 151 5.853 -43.57426.1031.00 46.62 C

ATOM 2754 N ILEB 152 3.777 -40.67022.6721.00 41.06 N

ATOM 2755 CA ILEB 152 4.251 -39.31222.8841.00 43.00 C

ATOM 2756 C ILEB 152 5.285 -39.28624.0051.00 46.11 C

ATOM 2757 O ILEB 152 4.979 -39.59625.1601.00 45.89 0 ATOM 2758 CB ILEB 152 3.080 -38.36323.2301.00 42.41 C

ATOM 2759 CG1 ILEB 152 1.959 -38.51522.1911.00 41.31 C

ATOM 2760 CG2 ILEB 152 3.563 -36.92423.2551.00 41.99 C

ATOM 2761 CD1 ILEB 152 2.373 -38.18420.7631.00 38.59 C

ATOM 2762 N ASNB 153 6.517 -38.93823.6461.00 49.26 N

ATOM 2763 CA ASNB 153 7.611 -38.85624.6061.00 52.72 C

ATOM 2764 C ASNB 153 8.170 -37.43524.6151.00 53.25 C

ATOM 2765 O ASNB 153 9.283 -37.18724.1451.00 53.62 0 A'.COM2766 CB ASNB 153 8.717 -39.85524.2431.00 55.44 C

A'POM2767 CG ASNB 153 9.260 -39.64622.8381.00 58.84 C

A'POM2768 OD1 ASNB 153 8.546 --39.82321.8471.00 60.97 0 A'POM2769 ND2 ASNB 153 10.531 --39.26622.7471.00 60.3? N

ATOM 2770 N GLYB 154 7.378 -36.50725.1461.00 52.78 N

ATOM 2771 CA GLYB 154 7.788 -35.11525.2111.00 52.71 C

ATOM 2772 C GLYB 154 8.170 ~-34.54923.8571.00 52.77 C

ATOM 2773 0 GLYB 154 7.662 -34.98722.8211.00 52.92 0 ATOM 2774 N SERB 155 9,061 -33.56123.8701.00 51.59 N

ATOM 2775 CA SERB 155 9.536 -32.93222.6461.00 50.81 C

ATOM 2776 C SERB 155 8.439 -32.17821.8751.00 49.55 C

AT01H2777 0 SERB 155 7.503 -31.63522.4661.00 48.94 0 ATOM 2778 CB SERB 155 10.177 -33.99521.7451.00 51.56 C

ATOM 2779 OG SERB 155 10.939 -33.40120.7071.00 53.85 O

ATOM 2780 N VALB 156 8.575 -32.15020.5521.00 48.22 N

ATOM 2781 CA VALB 156 7.632 -31.46519.6671.00 45.57 C

ATOM 2782 C VALB 156 6.260 -32.13719.6191.00 44.19 C

ATOM 2783 0 VALB 156 5.236 -31.47219.4251.00 43.28 0 ATOM 2784 CB VALB 156 8.194 -31.39918.2281.00 46.12 C

ATOM 2785 CG1 VALB 156 7.214 -30.68617.3071.00 46.02 C

ATOM 2786 CG2 VALB 156 9.544 -30.69318.2351.00 46.95 C

ATOM 2787 N GLYB 157 6.243 -33.45519.7811.00 41.73 N

ATOM 2788 CA GLYB 157 4.984 -34.17719.7471.00 41.16 C

ATOM 2789 C GLYB 157 4.064 -33.77120.8831.00 40.00 C

ATOM 2790 0 GLYB 157 2.849 -33.64620.6981.00 39.29 0 ATOM 2791 N LEUB 158 4.652 -33.56222.0581.00 39.15 N

ATOM 2792 CA LEUB 158 3.909 -33.16923.2491.00 38.35 C

ATUM 2793 C LEUB 158 3.403 -31.74023.0961.00 38.29 C

ATOM 2794 0 LEUB 158 2.232 -31.45523.3551.00 38.37 0 ATOM 2795 CB LEUB 158 4.814 -33.24624.4811.00 38.91 C

ATOM 2796 CG LEUB 158 4.234 -33.70025.8251.00 39.65 C

ATOM 2797 CD1 LEUB 158 5.201 -33.27726.9241.00 37.89 C

ATOM 2798 CD2 LEUB 158 2.857 -33.09726.0671.00 39.32 C

ATOM 2799 N ALAB 159 4.293 -30.84122.6811.00 37.29 N

ATOM 2800 CA ALAB 159 3.932 -29.43922.5021.00 36.84 C

ATOM 2801 C ALAB 159 2.782 -29.29521.5141.00 37,04 C

ATOM 2802 O ALAB 159 1.867 -28.49621.7211.00 36.83 0 ATOM 2803 CB ALAB 159 5.137 -28.65022.0171.00 36.73 C

ATOM 2804 N LYSB 160 2.836 -30.07020.4381.00 37.15 N

ATOM 2805 CA LYSB 160 1.796 -30.04519.4141.00 37.23 C

ATOM 2806 C LYSB 160 0.435 -30.43320.0091.00 36.56 C

ATOM 2807 O LYSB 160 -0.582 -29.79719.7181.00 36.14 0 ATOM 2808 CB LYSB 160 2.179 -31.00318.2831.00 40.16 C

ATOM 2809 CG LYSB 160 1.251 -31.00717.0841.00 43.77 C

ATOM 2810 CD LYSB 160 1.777 -31.99116.0401.00 46.63 C

ATOM 2811 CE LYSB 160 0.902 -32.03814.7951.00 48.08 C

ATOM 2812 NZ LYSB 160 1.457 -32.99313.7841.00 48.41 N

ATOM 2813 N ILEB 161 0.414 -31.47120.8451.00 35.10 N

ATOM 2814 CA ILEB 161 -0.835 -31.90521.4711.00 34.10 C

ATOM 2815 C ILEB 161 -1.358 -30.85822.4611.00 35.07 C

ATOM 2816 0 ILEB 161 -2.560 -30.60322.5211.00 32.85 0 ATOM 2817 CB ILEB 161 -0.666 -33.25922.2111.00 33.00 C

ATOM 2818 CG1 ILEB 161 -0.480 -34.39221.1961.00 33.76 C

ATOM 2819 CG2 ILEB 161 -1.882 -33.53323.0851.00 31.78 C

ATOM 2820 CD1 ILEB 161 -0.293 -35.76621.8161.00 32.90 C

ATOM 2821 N ARGB 162 -0.458 -30.25423.2341.00 35.90 N

ATOM 2822 CA ARGB 162 -0.865 -29.24124.2031.00 36.30 C

ATC>M2823 C ARGB 162 -1.422 -28.03923.4571.00 36.85 C

ATOM 2824 0 ARGB 162 -2.380 -27.40923.9021.00 37.83 0 ATOM 2825 CB ARGB 162 0.323 -28.79925.0651.00 37.14 C

ATOM 2826 CG ARGB 162 0.835 -29.84326.0461.00 38.52 C

ATOM 2827 CD ARGB 162 1.905 -29.22826.9391.00 39.80 C

ATOM 2828 NE ARGB 162 2.537 -30.17627.8521.00 39.98 N

ATOM 2829 CZ ARGB 162 :1.951 -30.69228.9291.00 41.37 C

ATOM 2830 NH1 ARGB 162 0.701 -30.35929.2351.00 41.73 N

ATOM 2831 NH2 ARGB 162 2.625 -31.52429.7141.00 38.64 N

ATOM 2832 N HISB 163 -0.819 -27.72722.3161.00 36.45 N

ATOM 2833 CA HISB 163 -1.264 -26.60521.5001.00 37.06 C

ATOM 2834 C HISB 163 -2.646 -26.84720.8901.00 36.46 C

ATOM 2835 0 HISB 163 -3.533 -;?6.00020.9911.00 35.42 0 ATOM 2836 CB HISB 163 -0.273 -26.34220.3651.00 38.30 C

ATOM 2837 CG HISB 163 -0.718 -25.26819.4231.00 40.58 C

ATOM 2838 ND1 HISB 163 -0.538 -23.92719.6841.00 41.41 N

ATOM 2839 CD2 HISB 163 -1.388 -25.33618.2481.00 41.74 C

ATOM 2840 CE1 HISB 163 -1.079 -23.21518.7121.00 43.31 C

ATOM 2841 NE2 HISB 163 -1.603 -24.04617.8281.00 43.34 N

ATOM 2842 N ASNB 164 -2.821 -27.99820.2431.00 33.60 N

ATOM 2843 CA ASNB 164 -4.096 -28.31319.6121,00 33.27 C

ATOM 2844 C ASNB 164 -5.207 -28,68320.5861.00 32.19 C

ATOM 2845 O ASNB 164 -6.382 -28.44320.3061.00 32.53 0 ATOM 2846 CB ASNB 164 -3.924 -29.44118.5931.00 33.75 C

ATOM 2847 CG ASNB 164 -3.110 -29.01617.3931.00 35.50 C

ATOM 2848 OD1 ASNB 164 -3.325 -27.94016.8341.00 36.41 0 ATOM 2849 ND2ASN B 164 -2.177 -29.86416.9801.00 35.10 N

ATOM 2850 N PHE B 165 -4.846 -29.27221.7211.00 31.13 N

ATOM 2851 CA PHE B 165 -5.844 -29.65622.7131.00 31.32 C

ATOM 2852 C PHE B 165 -5.441 -29.20724.1171.00 32.73 C

ATOM 2853 0 PHE B 165 -4.973 -30.00424.9331.00 31.18 0 ATOM 2854 CB PHE B 165 -6.068 -3:L.17322.6861.00 30.64 C

ATOM 2855 CG PHE B 165 -6.394 -31.71321.3221.00 30.39 C

ATOM 2856 CD1PHE 13165 -5.380 -32.01920.4181.00 30.48 C

ATOM 2857 CD2PHE B 165 -7.719 -31.91220.9371.00 31.21 C

ATOM 2858 CE1PHE B 165 -5.680 -32.51919.1991.00 30.35 C

ATOM 2859 CE2PHE B 165 -8.031 -32.41119.6721.00 31.55 C

ATOM 2860 CZ PHE B 165 -7.011 -32.71518.7771.00 31.51 C

ATOM 2861 N PRO B 166 -5.625 -27.90924.4131.00 33.84 N

ATOM 2862 CA PRO B 166 -5.296 -27.30425.7081.00 34.52 C

ATOM 2863 C PRO B 166 -6.033 -27.98026.8611.00 33.91 C

ATOM 2864 0 PRO B 166 -5.530 -28.04727.9821.00 33.64 0 ATC>M2865 CB PRO B 166 -5,747 -25.84925.5391.00 35.12 C

ATUM 2866 CG PRO B 166 -5.658 -25.62124.0651.00 37.35 C

ATOM 2867 CD PRO B 166 -6.197 -26.90423.4971.00 34.67 C

ATOM 2868 N GLN B 167 -7.228 -28.48226.5741.00 34.10 N

ATOM 2869 CA GLN B 167 -8.054 -29.12927.5851.00 34.73 C

ATOM 2870 C GLN B 167 -'7.785 -30.61827.8031.00 33.53 C

ATOM 2871 O GLN B 167 -8.250 -31.19328.7891,00 32.63 0 ATOM 2872 CB GLN B 167 -9.540 -:?8.92027.2531.00 38.51 C

ATOM 2873 CG GLN B 167 -10.025 -:?9.58225.9461.00 43.62 C

ATOM 2879 CD GLN B 167 -9.523 -28.88824.6801.00 44.63 C

ATOM 2875 OE1GLN B 167 -8.324 -28.78624.4461.00 44.93 0 ATOM 2876 NE2GLN B 167 -10.452 -28.41623.8571.00 97.75 N

ATOM 2877 N ALA B 168 -7.047 -31.24626.8911.00 31.73 N

ATOM 2878 CA ALA B 168 -6.753 -32.67027.0281.00 31.27 C

ATOM 2879 C ALA B 168 -5.944 -32.91128.2891.00 30.50 C

ATOM 2880 0 ALA B 168 -4.965 -32.21328.5431.00 30.43 0 ATOM 2881 CB ALA B 168 -5.979 -33.18125.8041.00 29.42 C

ATOM 2882 N ILE B 169 -6.347 -33.90229.0791.00 28.56 N

ATOM 2883 CA ILE B 169 -5.629 -34.20430.3041.00 28.78 C

ATOM 2884 C ILE B 169 -4.895 -35.53830.2541.00 29.09 C

A".'OM2885 O ILE B 169 -4.072 -35.82731.1251.00 30.57 O

A'COM2886 CB ILE B 169 -6.566 -34.20131.5321.00 29.11 C

ATOM 2887 CG1 ILEB 169 -7.625 -35.29331.3891.00 29.04 C

ATOM 2888 CG2 ILEB 169 -7.204 -32.81631.6971.00 28.83 C

ATOM 2889 CD1 ILEB 169 -8..437 -35.49332.6421.00 31.24 C

ATOM 2890 N ALAB 170 -5.181 -36.35729.2481.00 26.92 N

ATOM 2891 CA ALAB 170 -4.504 -3').64829.1351.00 26.14 C

ATOM 2892 C ALAB 170 -4.344 -38.05127.6731.00 25.94 C

ATOM 2893 0 ALAB 170 -5.122 -3'7.62226.8201.00 25.13 0 ATOM 2894 CB ALAB 170 -5.280 -38.72029.8991.00 23.97 C

ATOM 2895 N VALB 171 -3.338 -38.88027.3921.00 25.47 N

ATOM 2896 CA VALB 171 -3.071 -39.31726.0311.00 26.21 C

ATOM 2897 C VALB 171 -2.619 -40.76325.9681.00 28.05 C

ATOM 2898 0 VALB 171 -1.806 -41.20626.7851.00 28.88 0 ATOM 2899 CB VALB 171 -1.978 -38.43325.3691.00 27.56 C

ATOM 2900 CG1 VALB 171 -0.688 -38.49226.1841.00 27.78 C

ATOM 2901 CG2 VALB 171 -1.710 -38.90123.9401.00 25.51 C

ATOM 2902 N GLUB 172 -3.174 -41.50425.0141.00 28.87 N

ATOM 2903 CA GLUB 172 -2.798 -42.89924.7991.00 27.89 C

ATOM 2904 C GLUB 172 -3.077 -43.30423.3411.00 27.76 C

ATOM 2905 0 GLUB 172 -3.151 -42.43222.4731.00 26.23 0 ATOM 2906 CB GLUB 172 -3.482 -93.82025.8231.00 28.77 C

ATOM 2907 CG GLUB 172 -4.947 -43.54126.0961.00 29.21 C

ATOM 2908 CD GLUB 172 -5.822 -43.92624,9321.00 30.20 C

ATOM 2909 OE1 GLUB 172 -6.071 -4.3.06424.0631.00 30.20 O

ATOM 2910 OE2 GLUB 172 -6.247 -45.10124.8821.00 30.32 O

ATOM 2911 N METB 173 -3.244 -44.59223.0481.00 27.83 N

ATOM 2912 CA METB 173 -3.411 -44,99521.6461.00 26.52 C

ATOM 2913 C METB 173 -4.704 -45.68821.1781.00 25.60 C

ATOM 2914 0 METB 173 -4.851 -45.94719.9821.00 24.53 0 ATOM 2915 CB METB 173 -2.206 -45.87221.2341.00 25.27 C

ATOM 2916 CG METB 173 -0.824 -45.17121.3121.00 28.70 C

ATOM 2917 SD METB 173 0.671 -46.23921.0571.00 25.18 S

ATOM 2918 CE METB 173 0.540 -46.58519.3971.00 23.45 C

ATOM 2919 N GLUB 174 -5.639 -45.98222.0761.00 29.61 N

ATOM 2920 CA GLUB 174 -6.861 -46.67321.6481.00 25.46 C

ATOM 2921 C GLUB 174 -8.206 -46.03922.0041.00 25.65 C

ATOM 2922 O GLUB 174 -9.197 -46.22021.2801.00 24.77 O

ATOM 2923 CB GLUH 174 -6.853 -48.11422.1811.00 25.36 C

A':~OM2924 CG GLUB 174 --5.713 -48.98922.6491.00 26.37 C

ATOM 2925 CD GLUB 174 -4.384 -48.76822.3611.00 26.53 C

ATOtd2926 OE1 GLUB 174 -3.330 -48.97421.7321.00 27.43 0 ATOM 2927 OE2 GLUB 174 -4.380 -48.41223.5511.00 29.42 O

ATOM 2928 N ALAB 175 -8.247 -45.29423.1031.00 24.95 N

ATOLH2929 CA ALAB 175 -9.489 -44.69323.5881.00 24.92 C

ATOM 2930 C ALAB 175 -10.456 -44.11922.5531.00 23.76 C

ATOM 2931 0 ALAB 175 -11.628 - 44.49922.5151.00 24.67 0 ATOM 2932 CB ALAB 175 -9.171 -43.62724.6581.00 23.86 C

ATOM 2933 N THRB 176 -9.980 -43.21321.7111.00 23.51 N

ATOM 2934 CA THRB 176 -10.861 -42.58920.7361.00 22.92 C

ATOM 2935 C THRB 176 -11.350 -43.55419.6611.00 23.49 C

ATOM 2936 0 THRB 176 -12.481 -43.44319.1931.00 22.93 O

ATOM 2937 CB THRB 176 -10.179 -41.36620.0991.00 23.69 C

ATOM 2938 OG1 THRB 176 -9.654 -40.53321.1431.00 24.00 O

ATOM 2939 CG2 THRB 176 -11.192 -40.54219.2961.00 24.19 C

ATOM 2940 N ALAB 177 -10.517 -44.51519.2801.00 21.09 N

ATOM 2941 CA ALAB 177 -10.933 -95.49018.2801.00 23.33 C

ATOM 2942 C ALAB 177 -12.104 -46.31218.8271.00 23.47 C

ATOM 2943 0 ALAB 177 -13.058 -4.6.60818.1071.00 24.95 0 ATOM 2944 CB ALAB 177 -9.762 -46.40917.9281.00 20.70 C

ATOM 2945 N ILEB 178 -12.026 -46.69120.0991.00 23.79 N

ATOM 2946 CA ILEB 178 -13.079 -47.48020.7191.00 23.67 C

ATOM 2947 C ILEB 178 -14.335 -46.62820.8931.00 23.41 C

ATOM 2948 O ILEB 178 -15.439 -47.08620.6231.00 24.05 0 ATOM 2949 CB ILEB 178 -12.604 -48.05322.0751.00 25.30 C

ATOM 2950 CG1 ILEB 178 -11.490 -49.07121.8231.00 26.77 C

ATOM 2951 CG2 ILEB 178 -13.761 -48.73322.8081.00 23.86 C

ATOM 2952 CD1 ILEB 178 -10.911 -49.65923.0701.00 30.92 C

ATOM 2953 N ALAB 179 -14.166 -45.38021.3201.00 24.16 N

ATOM 2954 CA ALAB 179 -1.5.304-44.47521.4891.00 24.40 C

ATOM 2955 C ALAB 179 -16.014 -44.31720.1471.00 24.45 C

ATOM 2956 0 ALAB 179 -17.242 -44.34720.0711.00 26.34 0 ATOM 2957 CB ALAB 179 -14.820 -43.10721.9801.00 22.21 C

ATOM 2958 N HISB 180 -15.216 -44.12919.1011.00 24.51 N

A'.COM2959 CA HISB 180 -15.686 -43.95317.7251.00 25.14 C

A'T'OM2960 C HISB 180 -16.526 -45.14717.2691.00 23.79 C

A'POM2961 O HISB 180 -17.618 -44.97116.7281.00 22.49 0 ATOM 2962 CB HISB 180 -14.469 -43.77416.8041.00 24.66 C

ATOM 2963 CG HISB180 -19.801 -43.44615.3781.00 25.35 C

ATOM 2964 ND1 HISB180 -13.833 -43.09614.4591.00 23.47 N

ATOL42965 CD2 HISB180 -15.978 -43.43014.7071.00 24.40 C

ATOM 2966 CE1 HISB180 -14.398 -42.88013.2851.00 24.58 C

ATOM 2967 NE2 HISB180 -15.699 -4:3.07613.4071.00 25.34 N

ATOIK2968 N VALB181 -16.028 -46.35917.4841.00 22.51 N

ATOM 2969 CA VALB181 -16.785 -47.54317.0661.00 23.49 C

ATOM 2970 C VALB181 -18.111 -4'7.63317.8331.00 24.59 C

ATOM 2971 0 VALB181 -19.146 -4'7.93617.2381.00 25.37 0 ATOM 2972 CB VALB181 -15.970 -48.84617.2721.00 21.96 C

ATOM 2973 CG1 VALB181 -16.813 -50.05916.9171.00 22.06 C

ATOM 2974 CG2 VALB181 -14.742 -48.82116.3921.00 24.04 C

ATOM 2975 N CYSB182 -18.083 -47.36419.1401.00 24.01 N

ATCM 2976 CA CYSB182 -19.309 -47.39819.9481.00 24.75 C

ATOM 2977 C CYSB182 -20.285 -46.35919.4221.00 24.47 C

ATOM 2978 O CYSB182 -21.494 -46.59819.3461.00 23.55 0 ATOM 2979 CB CYSB182 -18.999 -47.09721.4201.00 25.08 C

ATC)M2980 SG CYSB182 -18.047 -48.36222.2861.00 27.75 S

ATOM 2981 N HISB183 -19.763 -45.19019.0731.00 24.85 N

ATOM 2982 CA HISB183 -20.602 -44.12518.5341.00 26.14 C

ATOM 2983 C HISB183 -21.336 -44.63017.2911.00 26.58 C

ATOM 2984 0 HISB183 -22.561 -44.51517.1821.00 26.78 0 ATOM 2985 CB HISB183 -19.740 -42.91918.1641.00 28.58 C

ATOM 2986 CG HISB183 -20.499 -41.81817.4941.00 30.51 C

ATOM 2987 ND1 HISB183 -21.260 -40.90318.1921.00 32.73 N

ATOM 2988 CD2 HISB183 -20.627 -91.49316.1861.00 31.07 C

ATOM 2989 CE1 HISB183 -21.821 -90.06117.3431.00 32.29 C

ATOM 2990 NE2 HISB183 -21.453 -40.39716.1191.00 34.08 N

ATOM 2991 N ASNB184 -20.590 -45.19816.3511.00 27.06 N

ATOM 2992 CA ASNB184 -21.197 -45.70515.1301.00 27.50 C

ATOM 2993 C ASNB184 -22.212 -46.82215.3801.00 27.27 C

ATOM 2994 0 ASNB184 -23.135 -47.00214.5871.00 26.90 0 ATOM 2995 CB ASNB184 -20.122 -46.18214.1991.00 27.82 C

ATOM 2996 CG ASNB184 -19.399 -45.02813.4621.00 28.72 C

ATOM 2997 OD1 ASNB184 -18.764 -45.21512.4221.00 30.03 0 ATOM 2998 ND2 ASNB184 -19.486 -43.83614.0431.00 26.31 N

A'COM2999 N PHEB185 -22.039 -47.57616.4641.00 27.01 N

ATOM 3000 CA PHEB185 -'2.980 -48.64916.8001.00 27.20 C

ATOM 3001 C PHEB 185 -24,070 -48.11417.738 1.0028.78 C

ATOf93002 0 PHEB 185 -24.963 -48.85618.158 1.0027.97 0 AT01~3003 CB PHEB 185 -22.263 -49.81317.493 1.0026.47 C

ATO1K3004 CG PHEB 185 -21.683 -50.82916.547 1.0026.42 C

ATOM 3005 CD1 PHEB 185 -20.417 -5().64315.988 1.0023.73 C

ATOM 3006 CD2 PHEB 185 -22.401 -51.98016.224 1.0023.88 C

ATOM 3007 CE1 PHEB 185 -19.872 -51.58515.128 1.0024.55 C

ATOM 3008 CE2 PHEB 185 -21.868 -52.93115.365 1.0025.66 C

ATOM 3009 CZ PHEB 185 -20.596 -52.73614.811 1.0025.31 C

ATOM 3010 N ASNB 186 -23.982 -46.82518.065 1.0028.99 N

ATOM 3011 CA ASNB 186 -24.939 -46.17418.955 1.0031.57 C

ATOM 3012 C ASNB 186 -25.027 -46.88420.310 1.0031.13 C

ATC>M3013 0 ASNB 186 -26.117 -47.09720.892 1.0030.87 0 ATC)M3014 CB ASNB 186 -26.321 -9.6.12118.299 1.0035.97 C

ATUM 3015 CG ASNB 186 -2'7.324-95.31419.100 1.0040.15 C

ATOM 3016 OD1 ASNB 186 -27.052 -94.17619.486 1.0042.43 0 ATC)M3017 ND2 ASNB 186 -28.494 -45.89719.353 1.0041.80 N

ATOM 3018 N VALB 187 -23.873 -47.25720.858 1.0029.72 N

ATOM 3019 CA VALB 187 -23.816 -47.93022.155 1.0029.65 C

ATOM 3020 C VALB 187 -23.135 -47.04023.196 1.0030.27 C

ATOM 3021 O VALB 187 -22.037 -46.53022.963 1.0030.26 0 ATOM 3022 CB VALB 187 -23.039 -49.26022.065 1.0029.20 C

ATOM 3023 CG1 VALB 187 -22.826 -49.83623.467 1.0029.10 C

ATOM 3024 CG2 VALB 187 -23.795 -50.25721.187 1.0029.27 C

ATOM 3025 N PROB 188 -23.787 -46.82924.356 1.0029.85 N

ATOM 3026 CA PROB 188 -23.206 -45.99525.413 1.0029.21 C

ATOM 3027 C PROB 188 -21.871 -46.56125.905 1.0028.00 C

A'COM3028 0 PROB 188 -21.717 -47.77026.053 1.0027.40 0 A'POM3029 CB PROB 188 -24.276 -46.02126.500 1.0029.25 C

ATOM 3030 CG PROB 188 -25.547 -46.14225.703 1.0031.81 C

ATOM 3031 CD PROB 188 -25.178 -47.19524.684 1.0029.64 C

ATOM 3032 N PHEB 189 -20.902 -45.68726.153 1.0027.63 N

ATOM 3033 CA PHEB 189 -19.599 -46.13926.621 1.0027.59 C

ATOM 3034 C PHEB 189 -18.998 -45.19127.651 1.0028.63 C

ATOM 3035 0 PHEB 189 -19.473 -44.07327.848 1.0029.75 0 ATOM 3036 CB PHEB 189 -18.617 -46.23225.455 1.0026.91 C

ATOM 3037 CG PHEB 1$9 -18.132 -44.89024.976 1.0028.80 C

ATOM 3038 CD1 PHEB 189 -18.857 -44.16724.036 1.002$.74 C

ATOM3039 CD2PHE B189 -16.981 -44.32325.513 1.0027.98 C

ATOM3040 CE1PHE B189 -18.444 -42.89923.646 1.0029.12 C

ATOM3041 CE2PHE B189 -1.6.563-43.06025.132 1.0026.39 C

ATOM3042 CZ PHE B189 -17.296 -42.34324.197 1.0027.96 C

ATOM3043 N VAL B190 -17.942 -45.65828.302 1.0028.57 N

ATOM3044 CA VAL B190 -17.208 -44.84929.251 1.0027.98 C

ATOM3045 C VAL B190 -15.751 -45.27729.139 1.0028.48 C

ATOM3046 0 VAL B190 -15.446 -46.47929.106 1.0027.58 0 ATOM3047 CB VAL B190 -7.7.720-45.02630.708 1.0028.35 C

ATOM3048 CG1VAL B190 -17.409 -46.41731.228 1.0028.06 C

ATOM3049 CG2VAL B190 -I7.101 -43.96231.594 1.0028.68 C

ATOM3050 N VAL B191 -I4.859 -44.29529.029 I.0028.05 N

ATOM3051 CA VAL B191 -13.427 -44.56228.936 1.0029.59 C

ATOM3052 C VAL B191 -12.775 -44.21930.272 1.0031.47 C

ATOM3053 O VAL B191 -13.024 -43.15330.849 1.0030.64 0 ATOM3054 CB VAL B191 -I2.761 -43.71927.817 1.0030.30 C

ATOM3055 CG1VAL B191 -11.238 -43.80027.923 1.0029.57 C

ATOM3056 CG2VAL B191 -13.213 -44.22026.456 1.0029.21 C

ATOM3057 N VAL B192 -11.956 -45.13930.769 1.0030.57 N

ATOM3058 CA VAL B192 -I1.257 -44.94432.030 1.0030.00 C

ATOM3059 C VAL B192 -9.795 -45.30431.793 1.0029.25 C

ATOM3060 0 VAL B192 -9.495 -46.29031.109 1.0026.13 0 ATOM3061 CB VAL B192 -11.839 -45.85233.145 1.0030.68 C

ATOM3062 CG1VAL B192 -I1.002 -45.72334.411 1.0032.29 C

ATOM3063 CG2VAL B192 -13.275 -45.46633.439 1.0030.12 C

ATOM3064 N ARG B193 -8.886 -44.50632.343 1.0027.95 N

ATOM3065 CA ARG B193 -7.464 -44.76032.156 1.0028.34 C

A~COM3066 C ARG B193 -6.628 -44.41533.385 1.0030.10 C

ATOM3067 O ARG B193 -6.683 -43.28933.888 1.0030.57 0 A'.POM3068 CB ARG B193 -6.944 -43.95530.959 1.0027.41 C

ATOM3069 CG ARG B193 -7.505 -44.37629.605 1.0027.00 C

A'.COM3070 CD ARG B193 -6.823 -45.63529.093 1.0027.17 C

ATOM3071 NE ARG B193 -7.227 -45.96927.731 1.0026.67 N

A'COM3072 CZ ARG B193 -8.383 -46.54027.403 1.0028.75 C

ATOM3073 NH1ARG B193 '9.264 -46.84728.346 1.0027.59 N

ATOM3074 NH2ARG B193 -8.649 -46.81826.127 1.0025.21 N

A'POM3075 N ALA B194 -5.859 -45.38733.867 1.0030.17 N

A"POM3076 CA ALA B194 '4.983 -45.17035.014 1.0031.78 C

A7.'OM3077 C ALA B 194 -3.721 -44.48634.484 1.0031.32 C

ATOM3078 0 ALA B 194 -3.123 -44.94933.517 1.0031.73 0 ATOM3079 CB ALA B 194 -4.630 -46.50135.671 1.0030.90 C

ATOM3080 N ILE B 195 -3.321 -43.38535.113 1.0031.88 N

A7.'OM3081 CA ILE B 195 -2.146 -42.63934.670 1.0032.43 C

ATOM3082 C ILE B 195 -0.836 -43.30335.086 1.0033.49 C

ATOM3083 0 ILE B 195 -0.499 -43.34636.271 1.0034.09 0 ATOM3084 CB ILE B 195 -2.182 -41.19535.209 1.0031.99 C

ATOM3085 CG1ILE B 195 -3.466 -40.49639.741 1.0030.93 C

ATOM3086 CG2ILE B 195 -0.956 -40.42834.724 1.0031.21 C

A9'OM3087 CD1ILE B 195 -3.623 -40.41933.225 1.0029.01 C

ATOM3088 N SER B 196 -0.102 -43.80634.093 1.0033.94 N

ATOM3089 CA SER B 196 7..166 -44.50334.310 1.0034.82 C

ATOM3090 C SER B 196 2.382 -43.58234.426 1.0037.55 C

ATOM3091 0 SER B 196 3.429 -43.98334.945 1.0035.87 0 ATOM3092 CB SER B 196 1.403 -45.49733.173 1.0034.10 C

ATOM3093 OG SER B 196 1.941 -44.83631.919 1.0033.09 0 ATOM3094 N ASP B 197 2.255 -42.36233.920 1.0039.10 N

ATOM3095 CA ASP B 197 3.345 -41.40133.990 1.0042.33 C

ATOM3096 C ASP B 197 2.843 -40.03233.561 1.0043.04 C

ATOM3097 0 ASP B 197 1.871 -39.92832.814 1.0042.61 0 ATOM3098 CB ASP B 197 4.504 -41.84033.097 1.0045.38 C

ATOM3099 CG ASP B 197 4.180 -41.73031.625 1.0050.02 C

ATOM3100 OD1ASP B 197 3.221 -42.39631.170 1.0053.87 0 ATOM3101 OD2ASP B 197 4.890 -40.97630.920 1.0051.51 0 ATOM3102 N VAL B 198 3.507 -38.98434.037 1.0042.89 N

ATOM3103 CA VAL B 198 3.111 -37.62333.711 1.0044.48 C

ATOM3104 C VAL B 198 4.177 -36.88732.908 1.0045.11 C

ATOM3105 0 VAL B 198 5.370 -37.00633.173 1.0043.23 0 ATOM3106 CB VAL B 198 2.793 -36.82834.991 1.0044.83 C

ATOM3107 CG1VAL B 198 2.399 -35.39434.638 1.0046.66 C

A~'OM3108 CG2VAL B 198 1.667 -37.51235.743 1.0045.76 C

ATOM3109 N ALA B 199 3.722 -36.12331.921 1.0047.51 N

A7.'OM3110 CA ALA B 199 4.602 -35.36531.041 1.0049.50 C

ATOM3111 C ALA B 199 5.558 -34.42731.774 1.0050.91 C

A7.'OM3112 0 ALA B 199 5.153 -33.65432.648 1.0051.36 0 ATOM3113 CB ALA B 199 3.766 -34.57130.040 1.0049.74 C

ATOM3114 N ASP B 200 6.830 -34.50931.398 1.0052.18 N

ATOM3115 CA ASP B200 7.887 -33.67931.965 1.0052.84 C

A'l.'OM3116 C ASP B200 8.290 -34.05533.386 1.0052.49 C

ATOM3117 0 ASP B200 9.109 -33.37433.998 1.0051.92 0 A9'OM3118 CB ASP B200 7.484 -32.20331.908 1.0053.91 C

ATOM3119 CG ASP B200 7.148 -31.74730.498 1.0055.27 C

A7.'OM3120 OD1ASP B200 8.001 -31.91229.597 1.0055.79 0 ATOM3121 OD2ASP B200 6.030 -31.22530.290 1.0055.57 0 ATOM3122 N GLN B201 7.723 -35.13833.908 1.0051.86 N

ATOM3123 CA GLN B201 8.064 -35.58935.255 1.0051.87 C

A9'OM3124 C GLN B201 8.786 -36.93035.178 1.0052.02 C

A7.'OM3125 O GLN B201 8.605 -37.64434.171 1.0052.27 O

ATOM3126 CB GLN B201 6.805 -35.71736.108 1.0050.41 C

ATOM3127 N SER B206 8.576 -47.57837.190 1.0054.60 N

ATOM3128 CA SER B206 8.612 -48.59336.095 1.0056.01 C

ATOM3129 C SER B206 7.216 -48.88935.557 1.0055.63 C

ATOM3130 0 SER B206 6.257 -49.01236.322 1.0055.73 O

ATOM3131 CB SER B206 9.239 -49.89136.603 1.0056.71 C

ATOM3132 OG SER B206 9.179 -50.90335.613 1.0058.08 0 ATOM3133 N PHE B207 7.106 -49.01134.237 1.0055.77 N

A9'OM3134 CA PHE B207 5.821 -49.28833.611 1.0056.20 C

A7.'OM3135 C PHE B207 5.217 -50.58534.133 1.0056.74 C

ATOM3136 O PHE B207 4.024 -50.65234.429 1.0056.27 O

ATOM3137 CB PHE B207 5.973 -49.37732.093 1.0055.84 C

ATOM3138 CG PHE B207 4.669 -49.56231.367 1.0056.23 C

ATOM3139 CD1PHE B207 3.634 -48.64231.527 1.0055.69 C

ATOM3140 CD2PHE B207 4.471 -50.65530.529 1.0055.96 C

ATOM3141 CE1PHE B207 2.419 -48.80730.863 1.0055.33 C

A~'OM3142 CE2PHE B207 3.257 -50.82929.860 1.0056.23 C

A~.'OM3143 CZ PHE B207 2.230 -49.90230.028 1.0055.26 C

A'COM3144 N ASP B208 6.050 -51.61434.250 1.0057.38 N

ATOM3145 CA ASP B208 5.595 -52.91134.730 1.0058.05 C

A':COM3146 C ASP B208 5.216 -52.86636.204 1.0057.36 C

A'.COM3147 0 ASP B208 4.255 -53.51236.625 1,0057.55 0 A'.COM3148 CB ASP B208 6.678 -53.96034.492 1.0059.99 C

A'.COM3149 CG ASP B208 7.125 -54.00333.044 1.0061.95 C

ATOM3150 OD1ASP B208 7.765 -53.02632.592 1.0062.96 0 ATOM3151 OD2ASP B208 6.825 -55.00432.357 1.0062.12 O

A~POM3152 N GLU B209 5.967 -52.10036.986 1.0056.53 N

ATOM 3153 CA GLU B209 5.679 -51.97138.410 1.0056.45 C

ATOM 3154 C GLU B209 4.342 -51.25438.588 1.0054.58 C

ATOM 3155 0 GLU B209 3.528 -51.61939.438 1.0054.32 0 ATOM 3156 CB GLU B209 6.788 -51.182.39.103 1.0058.27 C

ATOM 3157 CG GLU B209 8.144 -51.86139.063 1.0061.07 C

ATOM 3158 CD GLU B209 9.222 -51.03139.731 1.0062.48 C

ATOM 3159 OE1GLU B209 9.061 -50.69340.924 1.0063.35 0 ATOM 3160 OE2GLU B209 1Ø229-50.71839.064 1.0063.64 0 ATOM 3161 N PHE B210 9.132 -50.22237.779 1.0052.17 N

ATOM 3162 CA PHE B210 2.897 -49.45537.819 1.0049.65 C

ATOM 3163 C PHE B210 1.751 -50.38037.428 1.0048.64 C

ATOM 3164 0 PHE B210 0.699 -50.40438.068 1.0046.81 0 ATOM 3165 CB PHE B210 2.970 -48.29136.825 1.0047.98 C

ATOM 3166 CG PHE B210 1.629 -47.77636.410 1.0046.84 C

ATOM 3167 CD1PHE B210 0.910 -46.92237.237 1.0046.17 C

ATOM 3168 CD2PHE B210 1.051 -48.20235.217 1.0047.26 C

ATOM 3169 CE1PHE B210 -0.370 -46.50036.884 1.0046.30 C

ATOM 3170 CE2PHE B210 -0.228 -47.78834.856 1.0047.76 C

ATOM 3171 CZ PHE B210 -0.939 -46.93535.693 1.0046.73 C

ATOM 3172 N LEU B211 1.980 -51.13936.363 1.0047.95 N

ATOM 3173 CA LEU B211 1.003 -52.07735.830 1.0048.54 C

ATOM 3174 C LEU B211 0.557 -53.11136.870 1.0048.31 C

ATOM 3175 0 LEU B211 -0.633 -53.40037.004 1.0048.24 0 ATOM 3176 CB LEU B211 1.607 -52.78334.616 1.0048.64 C

ATOM 3177 CG LEU B211 0.749 -52.92533.360 1.0048.74 C

ATOM 3178 CD1LEU B211 0.224 -51.56332.919 1.0047.16 C

ATOM 3179 CD2LEU B211 1.592 -53.56832.262 1.0047.55 C

ATOM 3180 N ALA B212 1.518 -53.66137.604 1.0047.89 N

ATOM 3181 CA ALA B212 1.223 -54.65638.624 1.0048.14 C

ATOM 3182 C ALA B212 0.244 -54.13139.674 1.0048.15 C

ATOM 3183 0 ALA B212 -0.513 -54.90040.267 1.0050.46 O

ATOM 3184 CB ALA B212 2.515 -55.11339.291 1.0048.16 C

ATOM 3185 N VAL B213 0.254 -52.82239.901 1.0046.10 N

ATOM 3186 CA VAL B213 -0.640 -52.21540.881 1.0044.13 C

A~'OM31$7 C VAL B213 -1.955 -51.73340,266 1.0042.56 C

AroM 3188 o VAL B213 -3.043 -52.03940.773 1.0042.08 0 ATOM 3189 CB VAL B213 0.035 -51.00541.577 1.0044.62 C

AmOM 3190 CGiVAL B213 -0.966 -50.29742.481 1.0043.15 C

ATOM3191 CG2VAL B213 1..244 -51.47042.378 1.0045.72 C

ATOM3192 N ALA B214 -1.845 -50.98339.179 1.0039.89 N

ATOM3193 CA ALA B214 -3.007 -50.42238.494 1.0039.20 C

ATOM3194 C ALA B214 -3.953 -51.44037.856 1.0038.06 C

ATOM3195 0 ALA B214 -5.172 -51.25937.884 1.0037.40 0 ATOM3196 CB ALA B214 -2.547 -49.41337.440 1.0039.24 C

ATOM3197 N ALA B215 -3.394 -52.50137.282 1.0037.44 N

ATOM3198 CA ALA B215 -4.201 -53.51636.621 1.0037.40 C

ATOM3199 C ALA B215 -5.167 -54.16737.597 1.0038.39 C

ATOM3200 O ALA B215 -6.329 -54.41637.268 1.0037.56 0 ATOM3201 CB ALA B215 -3.299 -54.56835.986 1.0035.84 C

ATOM3202 N LYS B216 -4.682 -54.42838.805 1.0039.14 N

ATOM3203 CA LYS B216 -5.491 -55.05539.839 1.0040.15 C

ATOM3204 C LYS B216 -6.605 -54.12140.309 1.0040.09 C

ATOM3205 0 LYS B216 -7.767 -54.52840.408 1.0040.61 0 ATOM3206 CB LYS B216 -4.583 -55.47040.996 1.0042.07 C

ATOM3207 CG LYS B216 -3.351 -56.23140.503 1.0045.33 C

ATOM3208 CD LYS B216 -2.540 -56.87541.624 1.0048.00 C

ATOM3209 CE LYS B216 -1.339 -57.62041.047 1.0048.73 C

ATOM3210 NZ LYS B216 -0.668 -58.50842.033 1.0051.29 N

ATOM3211 N GLN B217 -6.258 -52.86740.586 1.0038.51 N

ATOM3212 CA GLN B217 -7.245 -51.88441.023 1.0038.56 C

ATOM3213 C GLN B217 -8.318 -51.70639.955 1.0037.91 C

ATOM3214 0 GLN B217 -9.513 -51.65240.257 1.0038.22 0 ATOM3215 CB GLN B217 -6.576 -50.53041.288 1.0038.34 C

ATOM3216 CG GLN B217 -5.694 -50.49142.525 1.0039.31 C

ATOM3217 CD GLN B217 -4.836 -49.23142.594 1.0040.43 C

ATOM3218 OE1GLN B217 -4.154 -48.98743.591 1.0042.68 0 A~OM3219 NE2GLN B217 -4.862 -48.43541.532 1.0038.03 N

A'.COM3220 N SER B218 -7.884 -51.61038.702 1,0037.55 N

ATOM3221 CA SER B218 -8.807 -51.42937.589 1.0036.24 C

ATOM3222 C SER B218 -9.791 -52.59837.476 1.0035.21 C

ATOM3223 0 SER B218 -10.964 -52.39537.165 1.0035.23 0 A'.COM3224 CB SER B218 -8.026 -51.25836.279 1.0035.00 C

ATOM3225 OG SER B218 -8.885 -50.87835.212 1.0034.97 p A'COM3226 N SER B219 -9.326 -53.81737.739 1.0035.28 N

A'POM3227 CA SER B219 -10.209 -54.98237.657 1.0036.04 C

A'.COM3228 C SER B219 -11.295 -54.90738.732 1.0036.81 C

ATOM3229 0 SER B219 -12.455 -55.23038.475 1.0036.76 0 ATOM3230 CB SER B219 -9.413 -56.28437.806 1.0037.35 C

ATOM3231 OG SER B219 -8.919 -56.45239.124 1.0039.36 0 ATOM3232 N LEU B220 -10.926 -54.47239.935 1.0035.62 N

ATOM3233 CA LEU B220 -11.908 -54.35341.005 1.0035.79 C

ATOM3234 C LEU B220 -12.880 -53.23940.653 1.0035.06 C

ATOM3235 0 LEU B220 -14.083 -53.36140.874 1.0034.73 0 ATOM3236 CB LEU B220 -11.222 -54.04942.343 1.0037.99 C

ATOM3237 CG LEU B220 -10.255 -55.13142.831 1.0039.09 C

A7.'OM3238 CD1LEU B220 -9.681 -54.72444.179 1.0039.31 C

ATOM3239 CD2LEU B220 -10.989 -56.46742.942 1.0040.51 C

ATOM3240 N MET B221 -12.352 -52.14840.105 1.0033.69 N

ATOM3241 CA MET B221 -7.3.185-51.02239.696 1.0033.67 C

ATOM3242 C MET B221 -14.228 -51.49938.683 1.0032.76 C

ATOM3243 O MET B221 -15.409 -51.15238.784 1.0032.78 0 ATOM3244 CB MET B221 -12.315 -49.92739.064 1.0033.32 C

ATOM3245 CG MET B221 -13.090 -48.85038.329 1.0033.24 C

ATOM3246 SD MET B221 -12.002 -47.75837.376 1.0036.06 S

ATOM3247 CE MET B221 -11.495 -48.84836.046 1.0034.60 C

ATOM3248 N VAL B222 -13.784 -52.29337.709 1.0032.73 N

ATOM3249 CA VAL B222 -14.676 -52.81436.672 1.0031.98 C

ATOM3250 C VAL B222 -15.799 -53.70837.285 1.0032.23 C

ATOM3251 0 VAL B222 -16.933 -53.57236.984 1.0032.60 0 ATOM3252 CB VAL B222 -13.889 -53.62335.601 1.0030.25 C

ATOM3253 CG1VAL B222 -14.851 -54.43834.732 1.0029.34 C

ATOM3254 CG2VAL B222 -13.092 -52.66734.716 1.0030.27 C

ATOM3255 N GLU B223 -15.324 -54.61838.148 1.0032.93 N

ATOM3256 CA GLU B223 -16.248 -55.53238.801 1.0036.12 C

ATOM3257 C GLU B223 -17.304 -54.71439.539 1.0036.20 C

A7.'OM3258 0 GLU B223 -18.504 -54.96339.413 1.0035.68 0 ATOM3259 CB GLU B223 -15.478 -56.41'739.773 1.0037.27 C

A"OM3260 CG GLU B223 -16.151 -57.72540.088 1.0042.05 C

A':COM3261 CD GLU B223 -15.303 -58.59140.985 1,0042.79 C

ATOM3262 OE1GLU B223 -14.088 -58.71940.714 1.0044.22 O

A'.COM3263 OE2GLU B223 -15.852 -59.14941.955 1.0046.56 0 A'.COM3264 N SER B224 -16.852 -53.72040.297 1.0036.69 N

ATOM3265 CA SER B224 -:L7.765-52.85541.037 1.0036.74 C

A':POM3266 C SER B224 -18.723 -52.09940.107 1.0036.51 C

ATOM3267 0 SER B224 -19.917 -51.98740.390 1.0036.85 0 ATOM3268 CB SER B224 -1.6.966-51.85641.881 1.0037.06 C

ATOM3269 OG SER B224 -7.7.833-50.94342.535 1.0043.30 0 ATOM3270 N LEU B225 -18.205 -51.57938.998 1.0036.12 N

ATOM3271 CA LEU B225 -19.035 -50.83638.047 1.0035.63 C

ATOM3272 C LEU B225 -20.086 -51.74737.403 1.0035.32 C

ATOM3273 0 LEU B225 -2.1.240-51.34737.199 1.0033.36 0 ATOM3274 CB LEU B225 -1.8.151-50.19936.969 1.0034.79 C

ATOM3275 CG LEU B225 -7.8.812-49.27235.945 1.0035.98 C

ATOM3276 CD1 LEU B225 -19.644 -48.20836.641 1.0035.52 C

ATOM3277 CD2 LEU B225 -17.727 -48.62435.094 1.0035.06 C

ATOM3278 N VAL B226 -19.684 -52.97237.079 1.0035.83 N

ATOM3279 CA VAL B226 -20.609 -53.93236.484 1.0037.88 C

ATOM3280 C VAL B226 -21.799 -54.12237.422 1.0039.16 C

ATOM3281 0 VAL B226 -22.953 -54.04537.003 1.0039.46 0 ATOM3282 CB VAL B226 -1.9.928-55.29536.249 1.0036.75 C

ATOM3283 CGl VAL B226 -20.964 -56.35035.902 1.0037.76 C

ATOM3284 CG2 VAL B226 -18.918 -55.17535.122 1.0036.37 C

ATOM3285 N GLN B227 -21.513 -54.34338.699 1.0041.70 N

ATOM3286 CA GLN B227 -22.568 -54.54639.684 1.0045.03 C

ATOM3287 C GLN B227 -23.400 -53.28339.872 1.0045.34 C

ATOM3288 0 GLN B227 -2.4.629-53.34139.958 1.0043.98 0 ATOM3289 CB GLN B227 -21.964 -54.97441.023 1.0046.57 C

ATOM3290 CG GLN B227 -20.887 -56.06240.912 1.0052.49 C

ATOM3291 CD GLN B227 -21.101 -57.02939.743 1.0055.05 C

ATOM3292 OE1 GLN B227 -22.218 -57.50539.499 1.0056.29 0 ATOM3293 NE2 GLN B227 -20.018 -57.33239.023 1.0054.05 N

ATOM3294 N LYS B228 -22.727 -52.14039.930 1.0046.07 N

ATOM3295 CA LYS B228 -2.3.412-50.87140.108 1.0046.73 C

ATOM3296 C LYS B228 -24.399 -50.66038.962 1.0046.91 C

ATOM3297 0 LYS B228 -25.523 -50.20239.179 1.0047.46 0 ATOM3298 CB LYS B228 -22.393 -49.72740.151 1.0049.02 C

ATOM3299 CG LYS B228 -22.985 -48.36540.476 1.0051.71 C

ATOM3300 CD LYS B228 -2.3.519-48.31541.901 1.0054.26 C

ATOM3301 CE LYS B228 -22.401 -48.49742.912 1.0054.86 C

ATOM3302 NZ LYS B228 -21.328 -47.48342.705 1.0055.58 N

ATOM3303 N LEU B229 -23.983 -51.00837.747 1.0046.08 N

ATOM3304 CA LEU B229 -24.843 -50.84736.578 1.0045.95 C

A7:'OM3305 C LEU B229 -25.969 -51.88036.530 1.0047.39 C

ATOM 3306 0 LEU B229 -27.057 -51.59036.042 1.0048.54 0 ATOM 3307 CB LEU B229 -24.012 -50.92635.289 1.0043.65 C

ATOM 3308 CG LEU B229 -22.973 -49.82035.051 1.0042.19 C

ATOM 3309 CDlLEU B229 -22.180 -50.12133.792 1.0040.19 C

ATOM 3310 CD2LEU B229 -23.665 -48.46534.934 1.0039.41 C

ATOM 3311 N ALA B230 -a?5.716-53.08137.090 1.0048.41 N

ATOM 3312 CA ALA B230 -26.732 -54.13237.030 1.0049.82 C

ATOM 3313 C ALA B230 -27.801 -53.92738.106 1.0050.77 C

ATOM 3314 0 ALA B230 -27.530 -53.23539.113 1.0051.90 0 ATOM 3315 CB ALA B230 -26.069 -55.49637.209 1.0048.33 C

HETATM3317 N9 ADE 233 -7.269 -38.516-0.556 0.8253.72 N

HF'sTATM3318 C8 ADE 233 -7.153 -37.960-1.775 1.5153.50 C

HETATM3319 N7 ADE 233 -6.174 -37.053-1.872 1.0453.80 N

HETATM3320 C5 ADE 233 -5.632 -37.038-0.611 0.4453.15 C

HETATM3321 C6 ADE 233 -4.568 -36.311-0.017 0.5052.87 C

HETATM3322 N6 ADE 233 -3.859 -35.422-0.711 0.9753.66 N

HETATM3323 N1 ADE 233 -4.292 -36.5621.321 1.2352.24 N

HETATM3324 C2 ADE 233 -5.026 -37.4712.010 0,8251.90 C

HETATM3325 N3 ADE 233 -6.059 -38.2141.536 0.6952.49 N

HETATM3326 C4 ADE 233 -6.300 -37.9380.212 1.1253.16 C

HETATM3327 N9 ADE 234 0.391 -44.98926.383 1.0257.54 N

HETATM3328 C8 ADE 234 0.805 -44.75827.646 1.8857.87 C

HETATM3329 N7 ADE 234 1.448 -43.59227.800 0.6257.09 N

HETATM3330 C5 ADE 234 1.437 -43.04926.540 1.0356.67 C

HI~TATM3331 C6 ADE 234 1.940 -41,83725.995 0.4756.73 C

HETATM3332 N6 ADE 234 2.579 -40.94726.751 1.0856.63 N

HETATM3333 Nl ADE 234 1.740 -41.61424.639 0.8557.11 N

HI'sTATM3334 C2 ADE 234 1.087 -42.53323.885 0.8556.67 C

HETATM3335 N3 ADE 234 0.570 -43.71724.306 0.7356.66 N

HETATM3336 C4 ADE 234 0.787 --43.90225.652 0.8656.89 C

HETATM3337 0 HOH 1 -8.313 --38.604-4.359 1.0042.19 0 HETATM3338 O HOH 2 -10.238 -43.102-1.867 1.0028.96 O

HETATM3339 0 HOH 3 -9.798 --44.7650.081 1.0034.71 0 HETATM3340 0 HOH 4 7.295 -40.353-1.411 1.0022.91 0 HETATM3341 O HOH 5 -3.776 -42.05912.935 1.0022.39 0 HETATM3342 0 HOH 6 -3.804 -48.29113.499 1.0019.63 O

HF,TATM3343 0 HOH 7 5.318 -39.5407.628 1.0024.38 0 Hf,TATM3344 0 HOH 8 -11.840 -36.75217.236 1.0027.01 0 Hf,TATM3345 O HOH 9 -3.679 -50.50915.022 1.0022.04 0 HFsTATM3346 O HOH 10 -1.427 -53.95716.422 1.0025.87 0 HETATM3347 0 HOH 11 -2.748 -38.36510.647 1.0026.54 0 Hf;TATM3348 0 HOH 12 -6.053 -48.30125.503 1.0034.44 0 HE;TATM3349 0 HOH 13 -17.180 -42.8017.406 1.0025.90 O

Hf;TATM3350 0 HOH 14 -15.487 -41.3519.224 1.0026.44 0 HE;TATM3351 0 HOH 15 -13.703 -46.864-5.426 1.0029.15 0 HE;TATM3352 0 HOH 16 6.536 -46.91714.698 1.0030.53 0 HE,TATM3353 0 HOH 17 -17.944 -41.915-7.303 1.0031.59 0 HE;TATM3354 0 HOH 18 -3.154 -39.1904.320 1.0026.51 0 HE~TATM3355 0 HOH 19 -8.940 -60.65324.508 1.0027.42 0 HE;TATM3356 0 HOH 20 2.665 -49.4638.624 1.0025.24 0 HE:TATM3357 0 HOH 21 -2.765 -55.47014.787 1.0029.39 0 HE:TATM3358 0 HOH 22 -0.868 -40.94621.252 1.0024.75 0 HE;TATM3359 0 HOH 23 -18.038 -67.146-7.244 1.0032.84 0 HE;TATM3360 0 HOH 24 -13.885 -37.07914.794 1.0025.88 0 HE:TATM3361 0 HOH 25 -JØ956-47.3440.668 1.0025.03 0 HE:TATM3362 0 HOH 26 -21.757 -42.67824.974 1.0025.10 0 HE:TATM3363 0 HOH 27 -21.994 -48.4464.231 1.0040.45 0 HE:TATM3364 0 HOH 28 -4.742 -51.54123.923 1.0031.83 0 HETATM3365 0 HOH 29 -1.610 -29.29928.383 1.0038.91 0 HE:TATM3366 0 HOH 30 0,102 -58.570-15.0961.0039.88 0 HE:TATM3367 0 HOH 31 4.118 -57.060-2.247 1.0036.91 0 HE;TATM3368 0 HOH 32 -6.230 -30.7066.369 1.0031.83 0 HE:TATM3369 0 HOH 33 2.396 -35.7157.040 1.0028.11 0 HE:TATM3370 0 HOH 34 -17.342 -42.82711.016 1.0026.30 0 HE:TATM3371 0 HOH 35 -10.596 -31.97629.891 1.0035.20 0 HE:TATM3372 0 HOH 36 -2.132 -32.84818.061 1.0029.55 0 HE:TATM3373 0 HOH 37 6.461 -48.6088.107 1.0034.09 0 HE:TATM3374 0 HOH 38 -9.764 -42.89912.262 1.0019.21 0 HE:TATM3375 0 HOH 39 -9.594 -47.363-8.414 1.0025.11 0 HE;TATM3376 0 HOH 40 -17.517 -67.0511.855 1.0033.89 0 HE:TATM3377 0 HOH 41 -24.632 -62.673-12.2731.0036.10 0 HE;TATM3378 0 HOH 42 -20.032 -47.48210.720 1,0031.76 0 HE:TATM3379 0 HOH 43 -3.174 -30.99126.864 1.0035.29 0 HE:TATM3380 0 HOH 44 -21.943 -49.5411.491 1.0032.89 0 HE:TATM33810 HOH 45 -8.173 -48.38833.984 1.0038.17 0 HE:TATM33820 HOH 46 -7.219 -52.33531.221 1.0031.37 0 HE:TATM33830 HOH 47 -18.610 -64.10538.500 1.0039.07 0 HE:TATM33840 HOH 48 2.990 -37.7668.206 1.0031.46 0 HE:TATM33850 HOH 99 -7.2.747-63.4576.931 1.0034.11 0 HE:TATM33860 HOH 50 -2.686 -46.90624.860 1.0034.57 0 HE:TATM33870 HOH 51 -1.1.462-32.90017.748 1.0036.25 0 HE;TATM33880 HOH 52 7.244 -47.736-4.172 1.0026.56 O

HE;TATM33890 HOH 53 -6.784 -58.75815.006 1.0032.79 0 HE;TATM33900 HOH 54 -0.421 -52.743-16.5321.0036.67 0 HE;TATM33910 HOH 55 -19.504 -47.4414.812 1.0041.31 0 HE;TATM33920 HOH 56 7.828 -43.13819.573 1.0033.94 0 HE;TATM33930 HOH 57 -24.509 -50.229-13.3831.0034.33 0 HE;TATM33940 HOH 58 -21.998 -43.82622.355 1.0034.07 0 HE;TATM3395O HOH 59 -0.269 -40.30515.108 1.0028.44 0 HE;TATM33960 HOH 60 -2.198 -59.5800.881 1.0031.19 0 HE;TATM33970 HOH 61 -1.7.665-47.4688.709 1.0037.76 0 HE;TATM33980 HOH 62 -1.1.121-40.2172.850 1.0028.80 0 HE;TATM33990 HOH 63 2.583 -26.23222.962 1.0037.87 0 HE;TATM34000 HOH 64 -1.325 -55.94132.759 1.0035.37 0 HE;TATM34010 HOH 65 -24.097 -59.295-12.9111.0035.30 0 HE;TATM34020 HOH 66 -20.545 -40.00640.729 1.0038.75 0 HE;TATM34030 HOH 67 2.400 -51.53610.878 1.0032.22 0 HE;TATM34040 HOH 68 2.009 -37.80210.845 1.0039.87 0 HE;TATM34050 HOH 69 -18.979 -31.95116.279 1.0037.94 0 HE;TATM34060 HOH 70 -13.029 -34.16637.733 1.0090.20 0 HE;TATM34070 HOH 71 -8.248 -49.98425.325 1.0042.16 0 HE;TATM34080 HOH 72 -4.000 -48.21927.623 1.0038.03 0 HE;TATM34090 HOH 73 -23.348 -47.814-0.159 1.0038.54 0 HE;TATM34100 HOH 74 -25.582 -53.55221.205 1.0027.64 0 HE;TATM34110 HOH 75 -23.830 -67.28036.560 1.0042.97 0 HE;TATM34120 HOH 76 -1.274 -62.1420.653 1.0038.74 0 HE;TATM34130 HOH 77 -26.981 -59.34533.114 1.0034.46 0 HE;TATM34140 HOH 78 11.564 -33.7583.157 1.0038.17 0 HE;TATM34150 HOH 79 -12.462 -64.9394.635 1.0031.01 0 HE~TATM34160 HOH 80 -2.384 -55.20318.514 1.0033.62 0 HE;TATM34170 HOH 81 -2.311 -32.391-10.0751.0032.80 0 HE;TATM34180 HOH 82 -3.426 -60.0293.551 1.0031.68 0 HE;TATM34190 HOH 83 -12.232 -41.042-3.439 1.0038.68 0 HE;TATM34200 HOH 84 -1Ø308-53.39720.833 1.0037.67 0 HE;TATM34210 HOH 85 -9.772 -32.46111.398 1.0023.10 0 HE;TATM34220 HOH 86 4.726 -50.194-12.3311.0036.91 0 HE;TATM34230 HOH 87 -11.537 -60.200-17.2241.0043.35 O

HE;TATM34240 HOH 88 -22.101 -66.54227.448 1.0031.36 O

HE;TATM34250 HOH 89 -4.214 -44.345-16.8821.0036.18 O

HE;TATM34260 HOH 90 8.258 -42.432-4.609 1.0040.68 0 HE;TATM34270 HOH 91 -5.854 -42.86742.546 1.0036.31 0 HE;TATM3428O HOH 92 -0.659 -50.263-17.6291.0036.27 O

HE;TATM34290 HOH 93 6.494 -37.46421.385 1.0040.13 0 HE;TATM34300 HOH 94 -1.8.005-33.15320.033 1.0039.42 O

HE;TATM34310 HOH 95 -19.728 -36.03528.484 1.0048.11 O

HE;TATM34320 HOH 96 -21.457 -62.9751.224 1.0042.35 0 HE;TATM34330 HOH 97 -10.406 -58.89840.027 1.0047.37 O

HE;TATM3434O HOH 98 -4.414 -66.0563.201 1.0046.01 0 HE;TATM34350 HOH 99 -30.710 -57.893-8.193 1.0043.56 0 HE;TATM34360 HOH 100 -9.291 -63.31639.140 1.0041.31 0 HE:TATM34370 HOH 101 -24.107 -53.65719.040 1.0037.01 0 HF:TATM34380 HOH 102 5.420 -28.99331.493 1.0044.67 0 HE:TATM34390 HOH 103 -26.316 -64.829-10.9841.0043.59 0 HE;TATM34400 HOH 104 -10.071 -45.199-12.4671.0039.12 0 HE:TATM34410 HOH 105 -16.742 -25.7319.685 1.0033.84 0 HE:TATM34420 HOH 106 -1.037 -35.241-3.500 1.0043.17 0 HE:TATM34430 HOH 107 -9.865 -55.039-17.7741.0040.01 0 HE:TATM34440 HOH 108 -2.2.438-63.00128.104 1.0045.48 0 HE:TATM34450 HOH 109 -14.891 -49.3905.150 1.0035.01 0 HE:TATM34460 HOH 110 9.850 -46.9477.821 1.0038.69 0 HE;TATM34470 HOH 111 -22.029 -33.82534.630 1.0047.12 0 HE;TATM34480 HOH 112 -19.467 -50.349-14.8061.0044.65 0 Hf;TATM34490 HOH 113 -2.2.322-68.568-11.8861.0056.35 0 Hf;TATM34500 HOH 114 10.012 -39.80814.217 1.0043.14 0 HFTATM34510 HOH 115 2.313 -62.416-2.231 1.0044.24 O

HFTATM34520 HOH 116 5.546 -34.975-5.768 1.0037.24 0 HFTATM3453O HOH 117 -0.531 -37.00810.018 1.0040.00 0 Hf;TATM3454O HOH 118 -24.401 -41.95725.595 1.0047.03 0 HETATM3455O HOH 119 -17.628 -62.484-12.8091.0030.69 0 HETATM34560 HOH 120 -16.287 -47.01750.145 1.0036.53 0 HE:TATM3457 0 HOH 121 -17.330 -59.594-13.2831.0045.18 0 HE:TATM3458 0 HOH 122 2.367 -57.544-13.9671.0045.31 0 HE;TATM3459 0 HOH 123 -7.025 -62.19225.663 1.0046.85 0 HE:TATM3460 0 HOH 124 -22.461 -62.28124.400 1.0046.02 0 HE:TATM3461 0 HOH 125 -14.866 -54.676-17.6251.0036.15 0 HE:TATM3462 0 HOH 126 -13.157 -64.94011.860 1.0049.89 0 HE:TATM3463 0 HOH 127 -27.020 -59.04123.861 1.0044.40 0 HE:TATM3464 0 HOH 128 3.476 -29.86033.178 1.0049.53 0 HE;TATM3465 0 HOH 129 -2.194 -61.7404.786 1.0041.02 0 HFTATM3466 0 HOH 130 8.324 -27.034-0.704 1.0040.03 0 HE;TATM3467 0 HOH 131 -12.814 -30.94728.900 1.0046.54 0 HE;TATM3468 0 HOH 132 7.191 -30.19924.755 1.0041.75 0 HE;TATM3469 0 HOH 133 -29.624 -51.12125.353 1.0047.34 0 HETATM3470 0 HOH 134 0.946 -37.99915.622 1.0043.27 0 HE;TATM3471 0 HOH 135 13.705 -35.1473.690 1.0047.02 0 HE;TATM3472 0 HOH 136 7.733 -34.742-4.581 1.0043.20 0 HE;TATM3473 0 HOH 137 -27.872 -49.19125.453 1.0041.60 0 HE;TATM3474 0 HOH 138 8.195 -47.525-6.616 1.0045.25 0 HF;TATM3475 0 HOH 139 -17.236 -29.45914.639 1.0046.49 0 HFTATM3476 0 HOH 140 -0.683 -28.87614.031 1.0045.63 0 HH.TATM3477 0 HOH 141 2.181 -34.92418.382 1.0041.49 0 HFTATM3478 0 HOH 142 -25.898 -48.016-12.1691.0041.74 O

HE'sTATM3479 0 HOH 143 -4.383 -57.05817.738 1.0046.86 0 HETATM3480 0 HOH 194 -10.10$ -29.55118.000 1.0040.55 0 HETATM3481 0 HOH 145 -21.792 -37.55134.285 1.0044.67 0 HFTATM3482 0 HOH 146 -17.984 -40.054-9.640 1,0040.47 0 HF'sTATM3483 0 HOH 147 2.603 -59.717-8.970 1.0042.08 0 HETATM3484 0 HOH 148 -20.513 -39.78620.555 1.0035.04 0 HI'sTATM3485 0 HOH 149 -7.950 --60.62321.896 1.0043.83 0 HETATM3486 0 HOH 150 -25.307 --53.89013.808 1.0045.08 0 HETATM3487 0 HOH 151 -31.396 -60.342-9.634 1.0038.22 O

HETATM3488 0 HOH 152 -19.146 --60.36114.831 1.0045.37 0 HI~TATM3489 0 HOH 153 -5.452 -26.49216.628 1.0045.94 0 H1,TATM3490 0 HOH 154 -13.202 --39.1811.434 1.0035.49 0 HI~TATM3491 O HOH 155 -2.345 --42.323-17.3851.0046.53 0 HI~TATM3492 0 HOH 156 3.964 -26.88725.194 1.0045.70 0 H13TATM3493 0 HOH 157 6.497 --47.39639.508 1.0048.32 0 HIsTATM3494 0 HOH 158 -18.877 --71.52535.982 1.0040.46 0 HF,TATM3495 0 HOH 159 -15.574 -43.145-19.0261.0041.72 0 HF~TATM3496 0 HOH 160 1.773 -52.554-14.9991.0044.99 0 HH~TATM3497 O HOH 161 -0.718 -54.80629.699 1.0039.46 0 HH,TATM3498 O HOH 162 -2.244 -50.23829.403 1.0040.40 0 HETATM3499 O HOH 163 -7.759 -66.8940.362 1.0049.88 0 HH~TATM3500 0 HOH 164 -1.706 -32.10310.775 1.0038.08 0 HH,TATM3501 O HOH 165 -10.140 -52.087-23.8621.0040.04 0 HFTATM3502 0 HOH 166 -8.252 -47.87536.995 1.0037.13 0 HETATM3503 0 HOH 167 -20.757 -37.29020.593 1.0041.36 0 HFTATM3504 O HOH 168 -14.891 -39.93842.300 1.0039.54 0 HF;TATM3505 0 HOH 169 -24.920 -42.93037.231 1.0039.99 0 HE;TATM3506 0 HOH 170 -10.964 -99.82048.267 1.0037.57 0 HETATM3507 0 HOH 171 2.325 -34.64011.538 1.0039.03 0 HFTATM3508 0 HOH 172 -6.036 -48.62138.296 1.0044.54 0 HF'sTATM3509 0 HOH 173 0.294 -46.34830.133 1.0053.13 0 HFTATM3510 O HOH 174 -0.034 -47.58526.532 1.0052.00 0 HFTATM3511 0 HOH 175 -0.810 -48.79922.851 1.0043.94 0 HFTATM3512 0 HOH 176 -0.710 -52.35728.670 1.0041.22 0 HETATM3513 0 HOH 177 -12.316 -43.05110.795 1.0019.67 0 HETATM3514 0 HOH 178 -9.536 -40.102-1.317 1.0096.54 0 HETATM3515 0 HOH 179 -11.707 -38.355-0.961 1.0039.12 0 HETATM3516 0 HOH 180 -8.798 -40.7011.188 1.0049.91 0 HETATM3517 0 HOH 181 -5.895 -42.9997.548 1.0050.24 0 HETATM3518 0 HOH 182 8.433 -27.67824.294 1,0051.23 0 HETATM3519 0 HOH 183 9.263 -45.120-6.249 1.0059.42 0 HETATM3520 0 HOH 184 5.631 -42.933-11.4821.0046.17 0 HI'sTATM3521 0 HOH 185 -21.355 -32.77614.854 1.0056.67 0 HI'sTATM3522 0 HOH 186 -19.958 -34.94920.149 1.0062.86 0 HETATM3523 0 HOH 187 :L0.791 --52.7266.946 1.0049.72 0 HETATM3524 0 HOH 188 9.145 -50.0240.773 1.0060.32 0 HETATM3525 O HOH 189 7.956 --50.363-1.952 1.0055.21 0 HI~TATM3526 0 HOH 190 -19.008 --41.653-16.5621.0061.42 0 HI~TATM3527 O HOH 191 -21.408 --40.830-19.0521.0053.77 0 HI~TATM3528 O HOH 192 -8.802 --55.29519.889 1.0045.57 0 H1,TATM3529 0 HOH 193 -25.706 -50.54414.801 1.0047.75 0 HI~TATM3530 0 HOH 194 -28.807 -54.769-8.063 1.0041.35 0 HI~TATM3531 0 HOH 195 -26.959 --46.90938.045 1.0052.04 0 H13TATM3532 0 HOH 196 -11.393 --41.63547.483 1.0058.82 0 HE)TATM35330 HOH 197 6.622 -26.12225.570 1.0055.34 0 HE;TATM35340 HOH 198 11.832 -50.2473.114 1.0056.79 0 HE:TATM35350 HOH 199 -13.181 -49.428-21.2081.0046.85 0 HE:TATM35360 HOH 200 3.379 -38.47229.679 1.0053.86 0 HE:TATM35370 HOH 201 -4.689 -65.153-4.131 1.0047.10 0 HE:TATM35380 HOH 202 -19.398 -41.31713.466 1.0055.28 0 HE:TATM35390 HOH 203 -18.476 -44.8708.366 1.0045.97 0 HE:TATM3540O HOH 204 -5.732 -62.32321.599 1.0053.22 0 HE:TATM35410 HOH 205 -23.153 -42.50720.255 1.0051.25 0 HE:TATM35420 HOH 206 -13.195 -30.86424.768 1.0053.65 0 HE:TATM35430 HOH 207 -14.115 -32.71827.562 1.0054.07 0 HE:TATM35440 HOH 208 -27.792 -63.643-3.291 1.0055.20 0 HE:TATM35450 HOH 209 -31.951 -57.7931.318 1.0045.79 0 HE:TATM35460 HOH 210 -?.5.012-66.888-3.013 1.0046.27 0 HE:TATM35470 HOH 211 -29.951 -63.315-2.842 1.0058.73 0 HE)TATM35480 HOH 212 3.712 -59.580-2.103 1.0051.63 0 HE:TATM35490 HOH 213 0.070 -35.2958.201 1.0052.89 O

HE:TATM35500 HOH 214 14.138 -41.2266.028 1.0055.74 0 HE;TATM35510 HOH 215 -26.140 -62.964-1.558 1.0040.58 0 CC)NECT331733183326 CC)NECT331933183320 CC)NECT332433233325 CC>NECT 3336 3327 3330 3335 END

~E 2 A'ICM CB C~U -3 87.070 54.24320.9071.00 51.96 A

A'I~M C~ C-~U -3 87.011 53.03519.9791.00 52.74 A

ATLM 3 CD C~(J -3 87.507 53.34618.5791.00 53.72 A
A

A2CM 4 CALC~J -3 87.591 52.41117.7551.00 52.92 A
A

A'nM 5 C~2C3~U -3 87.812 54.52618.2991.00 54.92 A
A

A'ICM C CPU -3 87.290 52.88423.0001.00 50.79 A

ATCM 7 O C~U -3 88.178 53.16423.8141.00 52.96 A
A

AICM 8 N CPU -3 86.545 55.24323.1151.00 51.15 A
A

A'ICM CA CPU -3 86.497 53.99022.3061.00 50.65 A

AEI 10 N PFD -2 86.969 51.63522.6671.00 47.38 A
A

ATCM 11 CA PHE -2 87.616 50.46123.2531.00 42.95 A
A

ATCM 12 CB PHE -2 89.140 50.53023.1081.00 42.27 A
A

AICM 13 C'GPHE -2 89.620 50.34121.7001.00 40.71 A
A

AICM 14 GD1Pi-~ -2 89.792 51.43120.8581.00 39.09 A
A

A'iCM C~ Pfd -2 89.851 49.06521,2001.00 39.78 A

A'I~2 CALPfd -2 90.186 51.25319.5351.00 36.96 A

ATOM 17 CQ PHE -2 90.244 48.87819.8801.00 38.73 A
A

AnM 18 CZ Pfd -2 90.410 49.97619.0461.00 36.92 A
A

A'ICM C PHE -2 87.260 50.24824.7181.00 40.32 A

AT'M 20 O FfiE -2 87.576 49.20425.2881.00 41.54 A
A

AZCM 21 N Sat -1 86.609 51.23125.3311.00 37.29 A
A

A'ICM CP.Sat -1 86.208 51.10726.7281.00 36.18 A

A'ICM CB Sat -1 86.875 52.18827.5811.00 36.59 A

A'1122 OG Sat -1 86.495 53.48627.1571. 39.65 A

A'It~2 C Sat -1 84.687 51.21326.8271.00 34.13 A

ATCM 26 O Sat -1 84.136 51.60527.8501.00 35.96 A
A

A'ICM N MEI' 1 84.011 50.85525.7461.00 32.83 A

A'~M 28 CA I~'r 1 82.559 50.89525.7121.00 32.06 A
A

A''tCM CS MET 1 82.076 51.41124.3541.00 35.84 A

A'ICM 03 MET 1 80.563 51.41224.1971.00 41.14 A

AnM 31 ~ MET 1 80.001 52.23822.6871.00 46.77 A
A

A'ICM CE MET 1 79.378 53.80023.3721.00 45.90 A

AnM 33 C ME,T 1 82.004 49.49925.9591.00 29.06 A
A

AIC~2 O MET 1 82.532 48.51225.4511.00 27.91 A

AnM 35 N LYS 2 80.955 49.41726.7661.00 26.04 A
A

A'iCM CA LYS 2 80.323 48.13627.0461.00 24.87 A

ABM 37 CB LYS 2 80.302 47.82628.5501.00 24.02 A
A

ATCM 38 03 LYS 2 79.733 46.43828.8651.00 25.52 A
A

ALCM 39 CD LYS 2 79.572 46.17230.3661.00 25.24 A
A

A'tCM CE LYS 2 80.907 46.13231.1011.00 26.32 A

A'tCM NZ LYS 2 80.719 45.86132.5591.00 28.08 A

ALCM 42 C LYS 2 78.906 48.25826.5261.00 23.45 A
A

A~ 43 O LYS 2 78.135 49.08027.0031.00 23.50 A
A

A'ICM N ILE 3 78.565 47.44425.5371.00 23.41 A

AnM 45 CA ILE 3 77.237 47.50024.9591.00 23.27 A
A

AICM 46 CB ILE 3 77.298 47.31223.4371.00 24.79 A
A

ALCM 47 O~ III 3 75.882 47.22222.8641.00 25.11 A
A

A'tCM O~.1LE 3 78.064 48.47822.8051.00 27.41 A

A'nM 49 Cue.ILE 3 78.349 48.29121.3271.00 31.66 A
A

A'~2 50 C ~E 3 76.319 46.44625.5531.00 23.78 A
A

A'ICM O ~E 3 76.606 45.25125.4931.00 24.26 A

A'ICM N GLY 4 75.218 46.90126.1381.00 21.99 A

ATOM 53 CA COY 4 74.258 45.98426.7151.0022.68 A
A

ATOM 54 C COY 4 73.243 45.57125.6651.0024.20 A
A

ATOM 55 0 COY 4 72.801 46.38524.8451.0023.21 A
A

ATOM 56 N II~E 5 72.883 44.29325.6771.0024.55 A
A

ATOM 57 CA ILE 5 71.915 43.76724.7261.0023.39 A
A

ATCM 58 CB ILE 5 72.604 42.90623.6551.0022.61 A
A

ATOM 59 O~ IIE 5 71.602 42.54822.5411.0021.73 A
A

ATOM 60 CALILE 5 73.798 43.67323.0741.0021.23 A
A

ATOM 61 CD1ILE 5 74.637 42.85222.1261.0020.34 A
A

ATOM 62 C ILE 5 70.930 42.90825.5021.0023.04 A
A

ATOM 63 O ILE 5 71.327 42.04426.2791.0024.31 A
A

ATOM 64 N ILE 6 69.645 43.16125.3051.0024.11 A
A

ATOM 65 CA ~E 6 68.621 42.40326.0051.0024.57 A
A

ATOM 66 CB ~E 6 67.819 43.30626.9771.0025.91 A
A

ATOM 67 Cfi2ILK 6 66.863 42.46027.8231.0022.51 A
A

ATOM 68 CX~.ILE 6 68.784 44.05827.8951.0026.93 A
A

ATOM 69 CD1IGE 6 68.109 45.05728.8301.0025.12 A
A

ATOM 70 C ILE 6 67.662 41.77625.0181.0024.44 A
A

ATOM 71 O ILE 6 67.077 42.46124.1881.0024.18 A
A

A'ICM N GAY 7 67.526 40.46025.1101.0026.45 A

ATOM 73 CA COY 7 66.616 39.72624.2511.0028.39 A
A

ATOM 74 C GAY 7 65.764 38.87425.1711.0030.64 A
A

ATOM 75 O COY 7 66.256 38.40926.2021.0030.49 A
A

ATCM 76 N ALA 8 64.498 38.66424.8181.0031.63 A
A

ATOM 77 GP.ALA 8 63.601 37.88025.6621.0034.87 A
A

ATOM 78 C8 ALA 8 62.183 38.42425.5511.0034.03 A
A

ATOM 79 C ALA 8 63.594 36.38225.3821.0038.10 A
A

ATCM 80 O ALA 8 63.456 35.57626.3071.0039.36 A
A

A'nM 81 N 1~'I' 9 63.744 36.00124.1181.0040.19 A
A

ABM 82 CA MEI' 9 63.714 34.58623.7661.0044.64 A
A

AZC~2 CB MET 9 62.672 34.34722.6741.0047.84 A

A'ICM ~ MET 9 61.248 34.63223.1141.0049.89 A

AnM 85 S'DMET 9 60.086 34.19021.8261.0053.38 A
A

ALCM 86 CE MET 9 60.300 32.39321.7911.0052.52 A
A

A'ICM C NAT 9 65.035 33.95123.3421.0045.25 A

A'ICM O 1~'I' 9 65.892 34.58622.7321.0044.28 A

A'ICM N C~J 10 65.159 32.66923.6631.0045.51 A

AnM 90 C~.C~J 10 66.338 31.87223.3651.0045.76 A
A

A'ICM C8 QU 10 66.040 30.40923.6891.0047.47 A

A'ICM 03 C~J 10 67.203 29.46123.4721.0051.93 A

AZCM 93 CD CST 10 66.827 28.01323.7441.0054.46 A
A

A2'CM CALCPU 10 67.706 27.13423.6151.0056.28 A

AnM 95 C~2C~J 10 65.651 27.75524.0831.0054.45 A
A

A'ICM C C3~U 10 66.853 31.97821.9311.0044.69 A

A'ICM O C~J 10 68.029 32.24821.7081.0042.87 A

A'ICM N C3~J 11 65.969 31.76520.9651.0044.36 A

A'ICM CA C~J 11 66.335 31.79419.5521.0046.13 A

A'ICM C8 (~J 11 65.072 31.92818.6931.0049.58 A

A'ICM 03 C~1 11 64.206 30.67218.6831.0051.69 A

AICM 102 CD C~J ll 63.653 30.32220.0581.0054.22 A
A

A'nM 103 CALC3~U 11 63.703 29.12820.4361.0054.78 A
A

A'ICM C~2C3~J 11 63.162 31.23720.7571.0054.08 A

A1CM 105 C C~tJ 11 67.384 32.82219.1081.0045.65 A
A

A'ICM O C~J 11 68.522 32.45318.8011.00 46.54 A

AZrM 107 N C3.~UU12 67.020 34.10019.0621.00 43.89 A
A

A'ICM C~.C3~1 12 67.978 35.11818.6271.00 43.08 A

A'nM 109 C8 C~IJ 12 67.307 36.48018.4721.00 43.85 A
A

A'!CM C~ C3~T 12 68.287 37.56218.0581.00 45.32 A

A'ICM CD CPU 12 67.763 38.95718.3011.00 45.00 A

AIC~2 OELCPU 12 68.497 39.92017.9951.00 44.91 A

AnM 113 ~ c~U 12 66.625 39.09018.7971.00 42.55 A
A

AZrM 114 C C~JtJ 12 69.165 35.27719.5701.00 40.99 A
A

ATOM 115 O (~JU 12 70.299 35.48319.1241.00 39.55 A
A

A'ICM N VAL 13 68.896 35.20520.8701.00 37.04 A

A'ICM CA VAL 13 69.949 35.34321.8641.00 35.80 A

A'ICM CB VAL 13 69.376 35.20123.2941.00 35.59 A

ATOM 119 CALUAL 13 70.491 35.23024.3181.00 35.47 A
A

AnM 120 Q~ VAL 13 68.390 36.33123.5631.00 36.58 A
A

AZrM 121 C UAL 13 71.027 34.29121.6321.00 35.29 A
A

A'iCM O UAL 13 72.217 34.56321.7941.00 36.44 A

A'ICM N ~t 14 70.607 33.09421.2361.00 34.36 A

A'ICM C~.'IHIt 14 71.531 31.99520.9771.00 33.26 A

AZrM 125 CB THIt 14 70.785 30.73520.5211.00 34.72 A
A

AT~2 126 OC;1'IF~2 14 69.737 30.43721.4501.00 37.80 A
A

A'nM 127 C~2~t 14 71.736 29.55520.4541.00 34.87 A
A

AnM 128 C 'IHIt 14 72.545 32.34619.8961.00 31.48 A
A

AICM 129 O ZHIt 14 73.743 32.10820.0581.00 28.82 A
A

AZCM 130 N L~J 15 72.063 32.90518.7911.00 31.05 A
A

ATOM 131 C~1LFxJ 15 72.943 33.27617.6851.00 32.03 A
A

A'ICM C8 LF~J 15 72.131 33.87016.5311.00 31.35 A

A'nM 133 OG LF11 15 71.223 32.88715.7941.00 31.89 A
A

A'ICM CD1L~J 15 70.504 33.61314.6721.00 32.59 A

AZrM 135 C~ L~J 15 72.056 31.73215.2321.00 30.88 A
A

ATOM 136 C LF~J 15 74.010 34.27218.1261.00 31.94 A
A

AZCM 137 O LExJ 15 75.180 34.13017.7791.00 32.01 A
A

A2CM 138 N L~U 16 73.596 35.27518.8961.00 31.92 A
A

ATOM 139 CA L'ExJ 16 74.512 36.29519.3881.00 32.23 A
A

AZrM 140 CB LFJJ 16 73.718 37.47519.9501.00 32.13 A
A

A'nM 141 CG L~1 16 72.873 38.21818.9061.00 32.76 A
A

AL~M 142 CD1L~J 16 72.054 39.32019.5581.00 30.72 A
A

AIC~2 CCeLETJ 16 73.795 38.80217.8581.00 32.48 A

AICM 144 C IFZJ 16 75.426 35.71820.4571.00 33.07 A
A

A'ICM O LF~T 16 76.616 36.02420.5071.00 34.82 A

A'nM 146 N ARG 17 74.861 34.87121.3061.00 33.63 A
A

A'ICM CA P~RG 17 75.610 34.24022 1.00 34.23 A
147 A .383 A'ICM CB Aid 17 74.674 33.35823.2061.00 36.28 A

AZCM 149 OG Ate 17 75.302 32.78324.4571.00 39.93 A
A

P.ZrM CD Ate 17 74.622 31.48724.8511.00 42.08 A

AZCM 151 I~ ARG 17 74.680 30.52323.7571.00 46.83 A
A

ATOM 152 CZ A~ 17 74.378 29.23423.8731.00 49.98 A
A

AICM 153 1~i1ARG 17 73.994 28.74125.0461.00 50.77 A
A

A'ICM 1~ ARG 17 74.460 28.43722.8151.00 50.59 A

A'ICM C ARG 17 76.751 33.39321.8211.00 35.29 A

AICM 156 O ARG 17 77.889 33.48822.2761.00 33.65 A
A

A'tCM N ASP 18 76.436 32.56620.8281.00 35.90 A

A'ICM CA ASP 18 77.424 31.69920.1911.00 36.93 A

ATOM 159 CB ASP 18 76.747 30.80419.1441.00 38.69 A
A

A'nM 160 C~ ASP 18 75.917 29.70219.7671.00 41.00 A
A

AICM 161 C~1 ASP 18 75.179 29.02319.0161.00 43.65 A
A

A'ICM C~ ASP 18 76.006 29.51021.0031.00 42.60 A

A'ICM C ASP 18 78.553 32.48319.5221.00 36.27 A

A'ICM O ASP 18 79.625 31.94019.2691.00 35.49 A

A'PC~I N LYS 19 78.305 33.75419.2231.00 35.53 A

AEI 166 CA LYS 19 79.315 34.58918.5901.00 34.86 A
A

A'ICM CB LYS 19 78.652 35.56117.6111.00 35.05 A

A'I~I 03 LYS 19 78.328 34.94916.2521.00 36.12 A

AIC~i CD LYS 19 77.526 35.91315.3891.00 39.29 A

A'IC~I CE LYS 19 77.521 35.50113.9231.00 39.70 A

A2CM 171 NZ LYS 19 78.895 35.57313.3481.00 40.95 A
A

A'~M 172 C LYS 19 80.172 35.36119.5901.00 34.21 A
A

A'ICM O LYS 19 81.131 36.02419.2041.00 35.91 A

A'ICM N aE 20 79.839 35.26720.8731.00 33.44 A

AZC~2 CA ~E 20 80.597 35.97521.9021.00 34.03 A

A'ICM CB ILE 20 79.798 36.07723.2271.00 32.39 A

A2CM 177 CJ~ ILE 20 80.664 36.70224.3181.00 30.69 A
A

AnM 178 cal ILE 20 78.537 36.91523.0141.00 29.94 A
A

A'ICM CDl ILE 20 77.759 37.17724.2851.00 26.97 A

A'nM 180 C ILE 20 81.947 35.32222.2051.00 36.26 A
A

A'I~I O ILE 20 82.032 34.11222.4241.00 36.28 A

A'PCM N C3IJ 21 83.000 36.13422.2271.00 36.69 A

A'IC~I CA C~J 21 84.343 35.63922.5121.00 37.48 A

AEI 184 CB C3xJ 21 85.380 36.49221.7961.00 39.60 A
A

A'I~M 03 CPU 21 85.029 36.84820.3751.00 43.99 A

ALCM 186 CD C3~J 21 85.849 38.01919.8871.00 46.54 A A

A'tCM C~1C3~T 21 87.090 37.95420.0181.00 49.10 A'ICM OF2C~J 21 85.261 38.99919.3801.00 45.85 A'ICM C (~J 21 84.602 35.72624.0101.00 37.65 ALCM 190 O C3~J 21 84.142 36.65724.6701.00 38.10 A A

A''ICM N A~1 22 85.358 34.77024.5391.00 36.84 A'hCM CA ACT 22 85.677 34.75225.9631.00 36.69 A'nM 193 C8 .a.9rT22 86.636 35.89326.3021.00 38.14 A A

A2CM 194 CG A~~T 22 87.860 35.90125.4071.00 39.43 A A

A'nM 195 OD1ASN 22 88.515 34.87325.2251.00 39.01 A A

A'I~t 1~ ASr1 22 88.176 37.06124.8431.00 38.47 A'ICM C ASN 22 84.382 34.90626.7391.00 36.60 A'ICM O A~1 22 84. 35 27 1. 34 .2 198 A 294 . . 00 2 A

AnM 199 N ARG 23 83.378 34.16226.2941.00 35.78 A A

AnM 200 CA .'9RG 23 82.066 34.19326.8981.00 37.30 A A

A'nM 201 B ARG 23 81.040 33.56125,9541.00 38.52 A A

A'nM 202 C~ ARG 23 79.639 33.45226.5461.00 40.58 A A

ALCM 203 CD At~G 23 78.607 33.08425.4881.00 43.34 A A

A'ICM NE ARG 23 78.773 31.72524.9751.00 45.76 ABM 205 CZ ARO 23 78.597 30.62525.6991.00 46.63 A A

A''LCM NH1ARG 23 78.248 30.71726.9761.00 48.99 ALCM 207 I~12A~ 23 78.764 29.43225.1451.00 45.37 A A

A'ICM C ARG 23 81.998 33.49928.2391.00 37.68 ALCM 209 O A~ 23 82.593 32.44528.4421.00 40.65 A A

A'ICM N C3N 24 81.276 34.12429.1591.00 37.72 ALCM 211 CA QN 24 81.045 33.57530.4851.00 38.32 A A

A'nM 212 CB QN 24 81.904 34.28431.5241.00 38.98 A A

AnM 213 C~ QN 24 83.388 34.04031.3111.00 39.86 A
A

A'ICM CD QN 24 84.211 34.58332.4361.00 39.85 A

A'ICM CAL CST 24 83.839 35.58233.0591.00 39.35 A

AICM 216 NE2 QN 24 85.350 33.94332.7071.00 39.43 A
A

A'ICM C CaN 24 79.569 33.81330.7641.00 38.92 A

AnM 218 O QN 24 78.970 34.73130.2031.00 37.65 A
A

ALCM 219 N 'II~t25 78.980 32.98031.6141.00 40.74 A
A

AICM 220 C~. 'IFS.25 77.570 33.12031.9301.00 42.67 A
A

A'nM 221 CB ~t 25 76.785 31.86731.5151.00 41.42 A
A

P:nM 222 OCiI.'IF~225 76.869 31.70830.0941.00 43.16 A
A

A'IC~t C~2 'If~t25 75.325 31.99131.9181.00 41.89 A

A2C~I C 'IHI~.25 77.330 33.39333.4051.00 44.60 A

A2C1~I O ~t 25 77.878 32.71634.2741.00 44.38 A

A'ICM N ILE 26 76.504 34.40233.6661.00 46.52 A

AnM 227 C~1 ~E 26 76.146 34.81335.0161.00 47.85 A
A

A'nM 228 C8 I!~ 26 76.499 36.30235.2471.00 48.62 A
A

ALCM 229 t~2 ~E 26 76.186 36.70136.6811.00 50.05 A
A

ALCM 230 C'~LILE 26 77.979 36.54134.9371.00 49.71 A
A

ALCM 231 Cfl11I~E 26 78.398 37.99635.0021.00 48.80 A
A

A'ICM C ~E 26 74.634 34.63435.1481.00 48.85 A

A'nM 233 O ILE 26 73.870 35.24334.4021.00 48.80 A
A

A'ICM N SER 27 74.206 33.79236.0831.00 49.04 A

A~ 235 C~ SER 27 72.782 33.55036.2861.00 49.68 A
A

ALCM 236 C8 S~t 27 72.518 32.04636.3911.00 50.58 A
A

A'ICM OG 8~R 27 71.128 31.77136.4491.00 53.47 A

AIC~t C Sat 27 72.280 34.26237.5431.00 50.23 A

ALCM 239 0 SE~t 27 72.764 34.00538.6461.0051.37 A
A

A'ICM N LExT 28 71.310 35.15837.3651.0049.77 A

AIC~2 C?~LEIJ 28 70.736 35.92638.4721.0048.53 A

A'nM 242 CB L~J 28 71.474 37.25538.6361.0049.25 A
A

A'ICM C.~LET 28 72.602 37.30939.6631.0050.75 A

A'ICM CDlLEZ1 28 73.253 38.68239.6161.0050.56 A

AnM 245 CS~LE1T 28 72.047 37.02141.0531.0050.46 A
A

A'nM 246 C LEIJ 28 69.247 36.22038.3101.0047.31 A
A

A'ICM O L~J 28 68.767 36.45037.2041.0045.82 A

ALCM 248 N GLY 29 68.533 36.22639.4321.0046.32 A
A

AICM 249 CA COY 29 67.109 36.50239.4241.0044.34 A
A

A'nM 250 C C3~Y 29 66.339 35.79538.3281.0043.72 A
A

A'ICM O COY 29 65.310 36.29337.8711.0043.88 A

AnM 252 N C3~Y 30 66.829 34.63537.9031.0042.63 A
A

A2CM 253 CA GLY 30 66.151 33.89436.8521.0040.88 A
A

A'IC~I C c~Y 30 66.553 34.35435.4611.0039.50 A

A'ICM 0 COY 30 65.894 34.02934.4731.0038.21 A

A'ICM N CYS 31 67.642 35.11235.3871.0038.39 A

A2CM 257 CA CYS 31 68.145 35.62334.1161.0038.62 A
A

A'ICM C8 CYS 31 68.137 37.15634.1011.0037.02 A

A'ICM 9~ CYS 31 66.508 37.90534.1721.0038.05 A

AnM 260 C CYS 31 69.564 35.16533.8521.0038.41 A
A

A'hCM O CYS 31 70.344 34.94134.7751.0038.72 A

A'ICM N C3.~T 32 69.897 35.04032.5771.0039.07 A

ABM 263 CA GC~U 32 71.239 34.65432.1901.0038.94 A
A

A'I~M CB QU 32 71.214 33.47531.2171.0042.00 A

ALCM 265 C~ CPU 32 71.296 32.11131.8811.0048.47 A
A

A'ICM C~ C~1 32 71.278 30.97830.8701.0051.58 A

A'I~I CALQ~J 32 70.223 30.76630.2301.0052.89 A

A'ICM C~'2CPU 32 72.322 30.30630.7091.0054.61 A

ATCM 269 C C~J 32 71.884 35.85231.5221.0036.60 A
A

ATOM 270 O C~U 32 71.291 36.47830.6441.0036.68 A
A

A'ICM N ILE 33 73.092 36.18131.9621.0034.20 A

A2CM 272 CA ILE 33 73.836 37.28731.3861.0032.20 A
A

ATOM 273 C8 ILE 33 74.181 38.35932.4351.0031.54 A
A

A'nM 274 Q~ ILE 33 74.951 39.49031.7781.0030.76 A
A

ATrM 275 O~.~E 33 72.899 38.90433.0681.0031.93 A
A

ATOM 276 C'fl1ILK 33 73.137 39.98634.0971.0033.67 A
A

ATOM 277 C ~ A 33 75.130 36.72330.8191.0032.04 A

ATOM 278 O III 33 75.915 36.09431.5351.0032.37 A
A

ATOM 279 N T'YR 34 75.339 36.93529.5261.0029.44 A
A

ATOM 280 CA T'YR 34 76.540 36.45328.8651.0028.35 A
A

ATOM 281 C8 T'YR 34 76.183 35.79127.5321.0028.10 A
A

ATOM 282 C~ T'YR 34 75.086 34.76727.6541.0030.54 A
A

ATrM 283 Ca1T'YR 34 75.314 33.54128.2801.0031.30 A
A

ATOM 284 CELTStR 34 74.275 32.61728.4541.0034.20 A
A

AZZM 285 CD2T'YR 34 73.794 35.04627.1971.0030.11 A
A

ATOM 286 C~2T'YR 34 72.753 34.13427.3661.0031.83 A
A

ATOM 287 CZ T'YR 34 72.998 32.92627.9941.0033.20 A
A

A'I~2 CH T'YR 34 71.964 32.03828.1731.0036.34 A

ATOM 289 C T'YR 34 77.458 37.63728.6201.0027.48 A
A

A'nM 290 O T'YR 34 77.067 38.61127.9741.0027.23 A
A

ATOM 291 N Tip. 35 78.671 37.55429.1511.0026.63 A
A

A'ICM c~ THIZ 35 79.655 38.60828.9831.0026.68 A

A'I~M CB 'IHIt 35 80.288 39.00630.3321.0027.26 A

A'nM 294 OG1'I~t 35 81.013 37.89530.8701.0027.89 A
A

A'I~I CG2~t 35 79.212 39.41931.3221.0024.52 A

A2C~I C 'IHR 35 80.744 38.09728.0491.0027.30 A

A~i 297 O 'If~.t35 80 . 36 27 1. 29.3 4 A 908 . . 00 A

A'I~M N GLY 36 81.483 39.02627.4591.0028.38 A

AnM 299 CA C3~Y 36 82.546 38.68026.5371.0028.02 A
A

A'IrM C GAY 36 82.577 39.76325.4801.0029.69 A

A''8=M O C3~Y 36 82.075 40.86425.7181.0028.76 A

A'I~M N C3N 37 83.154 39.46724.3181.0028.90 A

A'ICM CA CaN 37 83.215 40.44923.2451.0029.91 A

A'ICM C8 QN 37 84.663 40.83322.9251.0029.30 A

PAM 305 O3 QN 37 85.423 41.36524.1201.0029.19 A
A

A'nM 306 CD GtN 37 85.876 40.25725.0301.0028.24 A
A

A'ICM O~LQN 37 85.830 40.37526.2561.0028.58 A

A'IC~t I~2C3N 37 86.331 39.16424.4311.0028.31 A

A'ICM C QN 37 82.545 39.93521.9851.0030.99 A

A'ICM O QN 37 82.624 38.75621.6541.0030.16 A

A'ICM N LE~1 38 81.873 40.83621.2871.0033.05 A

A'ICM CA L'ExJ 38 81.202 40.48120.0571.0036.83 A

AICM 313 CB L~J 38 79.759 40.98220.0891.0036.29 A
A

A'nM 314 C~ L~7I1 38 78.806 40.44419.0301.0036.08 A
A

A'1CM CDlL~J 38 78.875 38.92618.9871.0034.88 A

AnM 316 CD2L~J 38 77.399 40.92219.3541.0035.67 A
A

A~ 317 C LFIT 38 81.991 41.16918.9611.0038.17 A
A

P~ 318 O ICJ 38 81.866 42.37318.7581.0040.97 A
A

A'IC~I N ASN 39 82.832 40.40018.2821.00 39.88 A

ATC~i CA ASD1 39 83.660 40.93417.2151.00 41.21 A

A'nM 321 CS ASrT 39 82.774 41.46016.0821.00 44.78 A
A

A'nM 322 Os ASrT 39 81.882 40.37415.4911.00 48.26 A
A

A'ICM CE~1ACT 39 82.370 39.40214.9101.00 48.26 A

ALCM 324 ND2ASN 39 80.568 40.53215.6461.00 49.52 A
A

AT~I 325 C ASrT 39 84.563 42.04317.7451.00 40.99 A
A

ALCM 326 0 A8r1 39 84.774 43.05517.0781.00 42.49 A
A

AnM 327 N COY 40 85.086 41.84818.9541.00 38.49 A
A

AnM 328 CA GAY 40 85.976 42.83019.5471.00 35.73 A
A

ATCM 329 C GLY 40 85.366 43.78720.5611.00 34.89 A
A

A'tcM O COY 40 86.062 44.27521.4501.00 33.95 A

A'ICM N 'II~2 41 84.070 44.05920.4441.00 33.13 A

A'ICM CA 'If~t 41 83.415 44.98821.3591.00 30.65 A

A'ICM CB 'Ii~t 41 82.247 45.71120.6661.00 29.35 A

A1CM 334 OG1'IHE2 41 82.719 46.32219.4611.00 31.21 A
A

ALCM 335 C~2'II~t 41 81.671 46.79021.5721.00 27.98 A
A

A'nM 336 C 'IHI~ 41 82.890 44.29222.6101.00 29.91 A
A

A'ICM O 'IHIt 41 82.237 43.25122.5241.00 28.96 A

A'ICM N Q.~J 42 83.187 44.86623.7731.00 26.72 A

AnM 339 CA C~.IU 42 82.727 44.28925.0291.00 27.52 A
A

A~ 340 C$ CPU 42 83.345 45.02026.2271.00 25.56 A
A

A'ICM 03 C~1 42 82.985 44.40127.5761.00 27.31 A

P:I~M ~ C~U 42 83.664 43.05727.8241.00 29.53 A

AICM 343 ~I.C3~U 42 83.159 42.28428.6641.00 28.73 A
A

A'IC~t DE2CPU 42 84.706 42.77327.1961.00 28.81 A

A'I~I C Q.~J 42 81.210 44.39925.0921.00 27.27 A

AnM 346 O C~J 42 80.647 45.49024.9641.00 26.92 A A

A'ICM N VAL 43 80.548 43.26525.2751.00 24.44 ABM 348 CA UAL 43 79.103 43.26225.3631.00 23.20 A A

P:IC~2 C8 UAL 43 78.456 42.59524.1191.00 22.89 A'ICM 0~1.UAL 43 78.872 43.32922.8541.00 21.47 A'ICM Ou2UAL 43 78.857 41.13324.0391.00 21.55 AICM 352 C UAL 43 78.643 42.51226.6021.00 23.38 A A

A'ICM O VAL 43 79.406 41.76427.2121.00 22.07 ALCM 354 N ALA 44 77.392 42.74726.9751.00 21.76 A A

ATC~I CA ALA 44 76.756 42.07928.1031.00 22.39 A'hCM CB ALA 44 76.646 43.01429.3071.00 21.22 AnM 357 C ALA 44 75.379 41.75427.5421.00 21.87 A A

ALCM 358 O ALA 44 74.566 42.65027.3111.00 23.10 A A

A'ICM N La1 45 75.149 40.47127.2951.00 22.53 A'IrM CTSLET 45 73.907 39.97826.7181.00 22.24 ALCM 361 CB L~J 45 74.224 38.99225.5891.00 21.63 A A

A'IrM 03 LF7IJ 45 73 . 38 24 1. 22 . O1 362 A 090 . , 00 A

AnM 363 CD1L~J 45 72.134 39.15924.2101.00 19.18 A A

A1CM 364 C~2ICJ 45 73.690 37.21323.9231.00 18.83 A A

A'ICM C L~J 45 73.046 39.28327.7571.00 23.14 A'1~M O LFLJ 45 73 . 38. 28. 1. 23 . 94 A1~! 367 N LEIT 46 71.871 39.84528.0131.00 24.50 A A

A'ICM CA LF1JJ 46 70.955 39.26528.9851.00 25.39 A'ICM CB ICJ 46 70.524 40.31130.0291.00 24.50 A'ICM C~ LF~J 46 69.502 39.83531.0791.00 25.61 A'ICM CDlLET 46 69.782 40.49732.4171.00 26.49 A'ICM CD2 LExJ 46 68.090 40.15730.6171.00 25.26 A'nM 373 C LF1J 46 69.730 38.70228.2911.00 25.10 A A

ALCM 374 O LExJ 46 69.107 39.36927.4651.00 26.10 A A

A'ICM N LYS 47 69.416 37.45328.6051.00 24.67 A'ICM CA LYS 47 68.238 36.80628.0541.00 25.44 AnM 377 CB LYS 47 68.475 35.30827.8811.00 26.62 A A

A'IC~I CG LYS 47 67.249 34.53327.4171.00 29.40 A'IC~2 CD LYS 47 67 . 33 27 1.0 34. 03 379 A 542 . . 0 A

A'ICM CE LYS 47 66.340 32.23226.9151.00 39.08 A'ICM 1~ LYS 47 66.646 30.76426.8531.00 39.47 A'ICM C LYS 47 67.181 37.04529.1211.00 25.46 A'IC~~I O LYS 47 67.235 36.46130.2071.00 24.90 A'IC~I N SER 48 66.245 37.93728.8311.00 25.04 A'IC1~I CA SEi~ 48 65.199 38.24429.7901.00 27.49 AZ'C~I CB SER 48 64.710 39.68029.6181.00 26.39 A'I~M OG SER 48 63.915 39.79328.4481.00 26.55 ALCM 388 C SQt 48 64.052 37.31229.5001.00 27.69 A A

A'ICM O Sit 48 64.043 36.61428.4881.00 31.90 A'ICM N GLY 49 63.082 37.28930.3921.00 27.71 A'ICM CA COY 49 61.934 36.45330.1401.00 24.48 A'ICM C C3~Y 49 61.025 37.29229.2691.00 21.27 AICM 393 O C3~Y 49 61.390 38.39128.8501.00 18.89 A A

A'ICM N ILE 50 59.836 36.77829.0071.00 22.35 A'nM 395 CA ILE 50 58.862 37.47928.1941.00 22.74 A A

AICM 396 CB ILE 50 57.983 36.45927.4401.00 23.91 A A

ALCM 397 OG2 ILE 50 56.783 37.14926.8151.00 21.89 A A

A'ICM O~l~E 50 58.848 35.73326.3991.0025.88 A

AnM 399 CD1~E 50 58.161 34.57725.7011.0025.48 A
A

A'ICM C IIrE 50 57.998 38.35829.0951.0022.90 A

A'nM 401 O ILE 50 57.667 37.97130.2191.0023.94 A
A

A'1C~2 N C3~Y 51 57.646 39.54828.6181.0020.36 A

A'IrM CA C~Y 51 56.810 40.41629.4261.0019.22 A

A1CM 404 C C~Y 51 57.540 41.60730.0091.0018.38 A
A

AEI 405 O COY 51 58.772 41.61630.1171.0019.48 A
A

A'I~I N LYS 52 56.764 42.60630.4091.0016.75 A

A1CM 407 C?~LYS 52 57.307 43.83930.9551.0017.07 A
A

ALCM 408 C~ LYS 52 56.180 44.86231.1311.0016.96 A
A

A'IC~i CG LYS 52 55.362 45.06429.8601.0021.55 A

A'ICM CD LYS 52 54.496 46.32329.8891.0023.05 A

A'ICM CE LYS 52 53.447 46.31230.9771.0021.92 A

A'ICM NZ LYS 52 52.494 47.45930.8151.0021.11 A

A'ICM C LYS 52 58.082 43.69232.2581.0015.48 A

A'tCM O LYS 52 59.164 44.26732.4031.0015.04 A

AnM 415 N UAL 53 57.537 42.92833.2011.0015.44 A
A

A'ICM CA VAL 53 58.194 42.74634.4871.0015.26 A

A'ICM C8 VAL 53 57.278 42.00535.4931.0014.62 A

A'IrM C~1VAL 53 58.063 41.65336.7591.0014.36 A

A'I~M C~ VAL 53 56.094 42.88635.8541.0012.28 A

AnM 420 C UAL 53 59.508 41.98834.3361.0016.48 A
A

A1CM 421 O VAL 53 60.530 42.40134.8821.0014.93 A
A

AnM 422 N ALA 54 59.477 40.88333.5981.0015.92 A
A

A1CM 423 CA ALp. 54 60.686 40.09533.3801.0018.44 A
A

A1CM 424 C8 ALA 54 60.381 38.88932.4981.0018.67 A
A

A'IrM C ALA 54 61.745 40.97332.7231.00 18.75 AnM 426 O ALA 54 62.908 40.95733.1181.00 19.07 A A

A'nM 427 N ALA 55 61.331 41 31.7241.00 20.10 A .748 A

AZCM 428 CA ALA 55 62.248 42.64131.0191.00 20.15 A A

ALCM 429 CB ALA 55 61.530 43.30129.8351.00 18.55 A A

A'ICM C ALA 55 62.787 43.70931.9731.00 20.62 A'ICM O ALA 55 63.975 44.02331.9611.00 21.18 A'ICM N ALA 56 61.904 44.27032.7951.00 21.37 A'ICM CA ALA 56 62.296 45.29433.7641.00 20.14 A'ICM CB ALA 56 61.067 45.79734.5141.00 17.61 AnM 435 C ALA 56 63.311 44.71434.7531.00 20.22 A A

ALCM 436 O ALA 56 64.348 45.32235.0401.00 18.70 A A

A'ICM N LBJ 57 62.992 43.53635.2731.00 21.13 A'ICM CA LF7tJ57 63.850 42.84036.2261.00 22.65 A'ICM C8 L~J 57 63.208 41.49236.5961.00 24.20 A'ICM C'~ LE~J 57 63.874 40.49937.5561.00 26.10 A'ICM CD1 L'EIJ57 62.910 39.36637.8311.00 25.61 A~2 442 CD2 LE7IJ57 65.149 39.94336.9621.00 29.36 A A

AnM 443 C ICJ 57 65.211 42.62435.5711.00 22.34 A A

AZCM 444 O LEZJ 57 66.247 42.91736.1621.00 21.47 A A

Aft 445 N C3~Y 58 65.196 42.11634.3421.00 22.05 A A

A'IC~I CA C3~Y 58 66.434 41.87033.6221.00 21.55 A~ 447 C C3.~Y58 67.210 43.14233.3411.00 21.04 A A

ABM 448 O Cd~Y 58 68.414 43.21633.5861.00 21.14 A A

AZCM 449 N ALA 59 66.522 44.14732.8131.00 20.11 A A

AZCM 450 CA ALA 59 67.158 45.41832.5181.00 21.76 A A

A'ICM C8 ALA 59 66. 141 46.37731.9291.00 21.23 A'ICM C ALA 59 67.782 46.02733.7831.00 22.67 A'IrM O ALA 59 68.881 46.57933.7351.00 22.55 A'I~2 N ~ 60 67 . 45 34 1. 22 . 31 454 A 082 , . 00 A

A'Il'~I CA 'IHIt60 67.591 46.47936.1651.00 20.44 ALCM 456 CB 'IHIt60 66.526 46.41237.2891.00 20.76 A A

A'IC~i OG1 ~t 60 65.364 47.14536.8851.00 20.49 An.M 458 C~2 'IHIt60 67.063 47.02038.5921.00 19.43 A A

A'ICM C 'If~t60 68.844 45.73636.6121.00 20.44 AZCM 460 0 ~ 60 69.833 46.35636.9971.00 19.14 A A

A'ICM N L~J 61 68.804 44.41136.5521.00 20.83 A2CM 462 CA LFxT 61 69.950 43.60036.9491.00 23.18 A A

AnM 463 C8 LF3J 61 69.604 42.10836.8901.00 23.43 A A

A'nM 464 CG LF~U 61 68.704 41.59738.0181.00 27.79 A A

AnM 465 CD1 IExJ 61 68.417 40.12437.8071.00 26.50 A A

AZCM 466 CD2 LF.~J61 69.382 41.82039.3741.00 27.99 A A

A'nM 467 C L~1 61 71.146 43.88036.0541.00 23.10 A A

ABM 468 O LFIJ 61 72.270 44.04036.5311.00 22.93 A A

A'ICM N I~1 62 70.898 43.93434.7511.00 23.22 A'ICI~i CA LET 62 71.959 44.19833.7911.00 24.22 A'ICM CB LE~J 62 71.387 44.20732.3711.00 23.30 A'ICM 03 LET 62 72.370 44.38131.2121.00 23.93 AZCM 473 C:D11LkLJ 62 73.394 43.24331.2251.00 21.51 A A

AnM 474 C~2 LD~J 62 71.598 44.39729.8951.00 22.66 A A

A~ 475 C LaT 62 72.630 45.54234.0861.00 25.40 A A

A'ICM O LE1J 62 73.855 45.63534.1631.00 25.03 AZCM 477 N LEx1 63 71.826 46.58534.2541.00 25.49 A A

ATCM 478 CA T~1 63 72.384 47.90234.5291.0028.17 A
A

ATCM 479 CB LFI1 63 71.268 48.94834.6091.0024.65 A
A

A'ICM C~ LE17 63 70.521 49.17333.2971.0026.55 A

ATCM 481 Cfl1IFxJ 63 69.504 50.28933.4631.0024.96 A
A

ATCM 482 C~ L~J 63 71.527 49.51432.1991.0024.64 A
A

A'ICM C L~J 63 73.186 47.90435.8201.0029.74 A

ATCM 484 O LF1T 63 74.298 48.41735.8701.0029.80 A
A

A'ICM N C~J 64 72.606 47.31736.8591.0031.43 A

AZC~t CA C~J 64 73.229 47.23838.1711.0035.02 A

AICM 487 C8 CPU 64 72.260 46.56439.1431.0036.82 A
A

A'nM 488 03 C3~U 64 71.113 47.45039.5531.0040.55 A
A

AICM 489 C~ C3~U 64 71.481 48.32740.7191.0043.50 A
A

ATOM 490 DE1C~JU 64 71.638 47.77441.8261.0044.63 A
A

A'ICM C~2C~J 64 71.624 49.55640.5331.0046.65 A

ATCM 492 C CST 64 74.570 46.51038.2211.0036.07 A
A

AT<M 493 0 C~'J 64 75.526 47.01838,7981.0036.92 A
A

AT'M 494 N HIS 65 74.641 45.32437.6241.0037.17 A
A

ATCM 495 C~.HIS 65 75.872 44.54137.6561.0039.68 A
A

A'rrM CB ~-ICS 65 75.547 43.05137.7631.0043.09 A

A'IrM C~ HIS 65 74.724 42.70438.9601.0048.58 A

A'tCM CD2HIS 65 73.570 42.00739.0771.0049.67 A

A'IrM I~1HIS 65 75.063 43.10540,2351.0050.40 A

A'IrM CE1HIS 65 74.150 42.67141,0861.0052.47 A

AT'M 501 NE2HIS 65 73.234 42.00240.4091.0052.06 A
A

ATCM 502 C HLS 65 76.848 44.73636.5091.0038.11 A
A

ATvM 503 O HIS 65 78.051 44.56036.6961.0039.07 A
A

AT'M 504 N CYS 66 76.352 45.08835.3281.0034.96 A
A

AnM 505 CP.CYS 66 77.247 45.25834.1911.0033.81 A
A

AnM 506 C8 CYS 66 76.779 44.38133.0271.0032.98 A
A

ALCM 507 9G CYS 66 76.786 42.60433.4181.0037.09 A
A

AnM 508 C CYS 66 77.440 46.69933.7341.0032.26 A
A

A'ICM O CYS 66 78.310 46.97932.9111.0031.54 A

AnM 510 N LYS 67 76.630 47.60734.2711.0032.50 A
A

ATCM 511 CA LYS 67 76.717 49.02933.9441.0032.22 A
A

A'nM 512 C8 LYS 67 77.806 49.69034.7961.0036.36 A
A

A'nM 513 O3 LYS 67 77.660 49.51736.3011.0039.81 A
A

A'I~M ~ LYS 67 76.794 50.60436.9131.0043.62 A

A'nM 515 CE LYS 67 76.793 50.50238.4381.0046.85 A
A

AnM 516 1~ LYS 67 76.027 51.60839.0861.0047.65 A
A

A'nM 517 C LYS 67 77.016 49.32532.4691.0031.18 A
A

ALCM 518 O LYS 67 77.924 50.10132.1671.0030.95 A
A

A'ICM N PRO 68 76.260 48.72431.5341.0029.67 A

AnM 520 ~ PR0 68 75.074 47.86231.6941.0029.31 A
A

A'nM 521 CA PR0 68 76.525 48.99330.1151.0027.70 A
A

A'ICM CS PR0 68 75.530 48.08129.4011.0027.93 A

A'ICM C~ PRO 68 74.374 48.02730.3621.0027.76 A

A'ICM C PRO 68 76.326 50.47129.7681.0028.25 A

AnM 525 O PRO 68 75.520 51.15730.3951.0026,84 A
A

At~M 526 N ASP 69 77.064 50.95728.7731.0027.87 A
A

ALCM 527 CA ASP 69 76.965 52.35928.3601.0026.85 A
A

A'ICM C8 ASP 69 78.153 52.73027.4741.0026.92 A

A'nM 529 03 ASP 69 79.468 52.59828.2031.0029.28 A
A

ALCM 530 OD1ASP 69 80.228 51.65427.9061.0028.43 A
A

A'nM 531 C~ ASP 69 79.729 53.43429.0901.0029.71 A
A

AZCM 532 C ASP 69 75.669 52.66727.6301.0025.95 A
A

AZrM 533 O ASP 69 75.128 53.76627.7451.0024.52 A
A

AZrM 534 N UAL 70 75.181 51.69426.8711.0023.09 A
A

A'ICM CA VAL 70 73.940 51.85726.1361.0022.45 A

A'nM 536 CB VAL 70 74.187 52.26724.6601.0023.24 A
A

A'ICM C~1VAL 70 74.925 53.59924.6021.0021.31 A

AZCM 538 C!~VAL 70 74.980 51.18523.9431.0020.40 A
A

A'nM 539 C VAL 70 73.235 50.52026.1531.0022.82 A
A

ABM 540 O UAL 70 73.845 49.49426.4401.0022.54 A
A

AnM 541 N ~ 71 71.945 50.53025.8541.0024.26 A
E
A

A2C~! CA ILE 71 71.188 49.29425.8311.0024.55 A

AZrM 543 C$ IIE 71 70.075 49.27226.9061.0023.00 A
A

A'ICM C1S2IIE 71 69.116 48.11526.6371.0022.16 A

AZrM 545 C7~LLIB 71 70.691 49.15428.3051.0022.87 A
A

ABM 546 CD1ILE 71 71.441 47.86528.5541.0022.70 A
A

A'i~2 C ILE 71 70.540 49.11324.4751.0025.63 A

ATOM 548 O ~E 71 69.959 50.04523.9251.0026.66 A
A

AZCM 549 N LLE 72 70.664 47.90823.9381.0025.58 A
A

A'ICM CA ~E 72 70.055 47.57822.6701.0023.81 A

AZrM 551 CB ILE 72 71.066 47.03121.6571.0023.49 A
A

A'ICM C~2~ 72 70.325 46.61020.3841.0020.16 A

ABM 553 CG1ILE 72 72 .12848 21. 1. 22 .3 A
A . 347 00 0 A'ICt2 C~1ILK 72 73.283 47.55020.5361.0021,70 A

ATCM 555 C IIE 72 69.058 46.46722.9431.0025.11 A
A

AICM 556 O IIE 72 69.444 45.36623.3521.0024.41 A
A

A'ICM N ASN 73 67.777 46.75222.7421.0025.54 A

ATOM 558 G?~A.a~173 66.772 45.72422.9441.0024.67 A
A

ALCM 559 CB A9rT 73 65.497 46.30223.5521.0025.03 A
A

ATOM 560 C'~A9r1 73 64.384 45.27023.6461.0024.42 A
A

ATCM 561 CE71ASL~T73 64.577 44.16924.1701.0026.05 A
A

ATCM 562 1~2A~1 73 63.218 45.61823.1331.0023.70 A
A

ATOM 563 C ASST 73 66.472 45.12621.5791.0024.39 A
A

ATOM 564 O A3d 73 66.176 45.85020.6301.0024.97 A
A

ATCM 565 N ~HIt 74 66.558 43.80521.4801.0024.94 A
A

ATOM 566 CA ~t 74 66.304 43.12920.2161.0026.72 A
A

ATCM 567 CB ~ 74 67.609 42.57819.6201.0026.37 A
A

ATOM 568 OG1'lift74 67.339 42.03218.3261.0030.98 A
A

A'nM 569 Os2'lift74 68.196 41.50120.5151.0025.42 A
A

ABM 570 C THIt 74 65.300 41.98720.3641.0025.22 A
A

ATOM 571 O 'IHIt74 64.853 41.68321.4631.0027.26 A
A

AT~t 572 N GAY 75 64.946 41.36519.2471.0025.30 A
A

ATL~I CA C3.Y 75 63.991 40.27019.2721.0024.98 A

ATZM 574 C C~Y 75 62.986 40.40318.1431.0024.51 A
A

A'ICM O Y 75 63.257 41.07817.1481.0024.55 A

ATCM 576 N SEft 76 61.825 39.76818.2901.0024.01 A
A

ATOM 577 CA Sit 76 60.794 39.84517.2631.0023.94 A
A

ATCM 578 CB SER 76 60.072 38.50217.1091.0023.54 A
A

ATCM 579 OG Sit. 76 59.266 38.20618.2371.0025.47 A
A

ATCM 580 C SE~t 76 59.784 40.92417.6111.0023.90 A
A

ATOM 582 O SER 76 59.922 41.62118.6161.0024.60 A
A

ATCM 582 N ALA 77 58.775 41.06516.7621.0023.16 A
A

ATOM 583 CA ALA 77 57.724 42.04516.9721.0022.27 A
A

AnM 584 CS AL~~177 58.291 43.45416.9271.0022.84 A
A

ABM 585 C ALA 77 56.684 41.88215.8861.0021.99 A
A

AnM 586 0 ALA 77 56.963 41.31314.8361.0021.34 A
A

AnM 587 N (~Y 78 55.484 42.38016.1501.0022.27 A
A

A'ICM CA (~Y 78 54.429 42.30615.1661.0024.33 A

A2CM 589 C COY 78 54.474 43.60214.3911.0026.19 A
A

A'ICM O GLY 78 54.405 44.67214.9881.0027.56 A

AnM 591 N C3~Y 79 54.616 43.51313.0701.0027.67 A
A

A'ICM CA GZY 79 54.670 44.71012.2471.0027.98 A

A'ICM C C3~Y 79 53.310 45.36212.0941.0028.80 A

A'IC~2 O G3~Y 79 52.315 44.68412.8561.0029.44 A

A1CM 595 N LBT 80 53.266 46.6$212.2381.0029.83 A
A

A'PCM CA LE~J 80 52.021 47.43012.1171.0031.23 A

ABM 597 CE IFZT 80 51.749 48.20113.4141.0028.90 A
A

A~2 598 Cu LE~J 80 51.515 47.37014.6871.0030.50 A
A

AnM 599 Ca1LExJ 80 51.443 48.29315.9071.0028.41 A
A

AnM 600 C'D2LFiT 80 50.231 46.56614.5561.0027.06 A
A

A'nM 601 C LEx1 80 52.081 48.38910.9231.0032.63 A
A

A2CM 602 O LF1T 80 51.057 48.70110.3151.0033.55 A
A

A'ICM N ALA 81 53.285 48.85310.5951.0034.37 A

AICM 604 CA ALA 81 53.481 49.7529.460 1.0035.03 A
A

AZCM 605 C8 ALA 81 54.892 50.3059.475 1.0034.79 A
A

A2CM 606 C ALA 81 53.235 48.9428.183 1.0036.99 A
A

A'ICM O ALA 81 53.764 47.$408.025 1.0036.08 A

AnM 608 N PRO 82 52.443 49.4957.247 1.0038.49 A
A

ABM 609 CD PRO 82 52.016 50.9067.250 1.0039.03 A
A

A'ICM CA PRO 82 52.091 48.8525.975 1.0038.88 A

A'PCM C8 PRO 82 51.256 49.9235.270 1.0039.85 A

AnM 612 CG PRO 82 51.852 51.1945.777 1.0039.52 A
A

A'ICM C PRO 82 53.220 48.3155.097 1.0039.69 A

A'nM 614 O PRO 82 53.067 47.2784.458 1.0039.25 A
A

A'1CM N ~ 83 54.353 49.0035.061 1.0040.71 A

AnM 616 CA 'IF~t83 55.454 48.5464.221 1.0041.97 A
A

A'ICM C8 ~t 83 56.393 49.7103.858 1.0042.71 A

A'ICM aG"1ZHIt 83 56.952 50.2675.053 1.0043.84 A

A'ICM OG2~t 83 55.626 50.7903.112 1.0042.81 A

AEI 620 C ~llt 83 56.281 47.4274.846 1.0041.82 A
A

ALCM 621 O ~t 83 57.208 46.9084.218 1.0043.24 A
A

AnM 622 N LEt1 84 55.945 47.0466.074 1.0040.70 A
A

A'ICM CA LEx1 84 56.682 45.9906.758 1.0037.99 A

A'ICM C8 LFIJ 84 56.527 4b.1218.274 1.0036.38 A

AZ'CM CG LBJ 84 57.286 47.2478.973 1.0035.67 A

ALCM 626 CD1LEZT 84 56.882 47.29910.4341.0034.13 A
A

A'ICM CDZLEtJ 84 58.783 47.0228.835 1.0035.17 A

AnM 628 C LE;J 84 56.264 44.5896.344 1.0037.36 A
A

AIC~2 O LEZT 84 55.079 44.2706.2$9 1.0035.85 A

AnM 630 N LYS 85 57.259 43.7596.058 1.0036.23 A
A

A'ICM CA LXS 85 57.042 42.3715.681 1.0036.84 A

ALCM 632 C8 LY5 85 57.561 42.1114.259 1.0039.14 A
A

AnM 633 03 LYS 85 56.965 43.0363.198 1.0043.51 A
A

AnM 634 CD LYS 85 57.567 42.8071.807 1.0045.38 A
A

ABM 635 CE LYS 85 57.173 41.4521.228 1.0047.81 A
A

ALCM 636 NZ LYS 85 57.675 41.247-0.1681.0049.90 A
A

ABM 637 C LYS 85 57.849 41.5556.686 1.0036.12 A
A

ALCM 638 O LYS 85 58.766 42.0817.325 1.0033.97 A
A

AnM 639 N VAL 86 57.515 40.2806.838 1.0035.62 A
A

ALCM 640 CA VAL 86 58.253 39.4397.769 1.0035.15 A
A

A2CM 641 CB UAL 86 57.820 37.9607.666 1.0035.93 A
A

A'ICM 031VAL 86 58.832 37.0698.374 1.0035.51 A

ABM 643 032UAL 86 56.447 37.7788.295 1.0036.55 A
A

A1CM 644 C VAL 86 59.742 39.5457.461 1.0034.41 A
A

A'iCM 0 UAL 86 60.146 39.4936.298 1.0035.67 A

A'ICM N COY 87 60.550 39.7048.504 1.0032.69 A

A'ICM CA Q~Y 87 61.985 39.8078.320 1.0030.01 A

A'ICM C COY 87 62.504 41.2328.344 1.0030.06 A

A'nM 649 O COY 87 63 .65641.4658.711 1.0031.71 A
A

AnM 650 N ASP 88 61.665 42.1887.955 1.0027.96 A
A

A'It~t CA ASP 88 62.070 43.5917.948 1.0027.28 A

A'iCM C8 ASP 88 60 . 44 7 . 1. 27 . A
652 A 987 . 297 00 6 7 ALCM 653 OG ASP 88 60.840 44.1595.808 1.0029.18 A
A

A'iCM C~1ASP 88 59.919 44.7175.172 1.0029.84 A

A't~M ODeASP 88 61.654 43.3715.273 1.0028.96 A

A'ICM C ASP 88 62.400 44.1039.352 1.0027.18 A

AnM 657 O ASP 88 61.963 43.53910.3571.0025.92 A
A

AEI 658 N ILE 89 63.173 45.1819.408 1.0026.62 A
A

A'I~M CA B.E 89 63.615 45.74710.6751.0025.71 A

AZCM 660 C8 ILE 89 65.082 46.20510.5701.0026.48 A
A

ALCM 661 C~2IGE 89 65.594 46.63511.9351.0025.73 A
A

A'ICM Cpl~E 89 65.938 45.0869.975 1.0024.09 A

A'ICM CD1IT~EE89 66.040 43.85510.8391.0023.17 A

ATrM 664 C ILE 89 62.809 46.94511.1541.0025.15 A
A

ATOM 665 O 7ZE 89 62.358 47.76310.3561.0025.75 A
A

ATOM 666 N VAL 90 62.622 47.03812.4661.0023.60 A
A

A'IC~I C~ VAL 90 61.926 48.17813.0391.0022.51 A

AnM 668 C8 VAL 90 60.589 47.80013.7141.0022.01 A
A

ATOM 669 ~L VAL 90 59.540 47.54812.6501.0021.96 A
A

ATOM 670 C~2VAL 90 60.763 46.57514.5991.0023.55 A
A

AnM 671 C VAL 90 62.859 48.79214.0611.0023.74 A
A

ATrM 672 O UAL 90 63.423 48.09614.9111.0023.85 A
A

ATOM 673 N VAL 91 63.042 50.10123.9471.0024.36 A
A

ATCM 674 CA UAL 91 63.913 50.83814.8381.0023.39 A
A

A'PCM (~ UAL 91 64.982 51.61114.0601.0023.99 A

ATOM 676 03LUAi~ 91 65.909 52.34715.0311.0022.46 A
A

ATOM 677 c~2UAL 91 65.766 50.64913.1731.0021.69 A
A

A'IC~2 C VAL 91 63.063 51.82615.5921.0024.26 A

AZC~2 O UAL 91 62.300 52.59415.0061.0026.40 A

AICM 680 N ~t 92 63.195 51.79816.9051.0024.48 A
A

ATOM 681 C1AgR 92 62.432 52.69217.7441.0025.04 A
A

ATrM 682 C8 Sat 92 62.333 52.12819.1531.0025.32 A
A

ATOM 683 DG ~t 92 63.609 52.18819.7741.0024.15 A
A

ATOM 684 C SER 92 63.060 54.06317.8601.0025.92 A
A

ATOM 685 0 SER 92 64.278 54.19818.0161.0024.92 A
A

ATOM 686 N ASP 93 62.223 55.08517.7721.0026.56 A
A

A'ICM C~1ASP 93 62.693 56.43617.9981.0028.08 A

ATCM 688 C$ ASP 93 62.340 57.38316.8371.0029.62 A
A

ATOM 689 C~ ASP 93 60.859 57.45016.5421.0032.86 A
A

AZrM 690 OD1ASP 93 60.499 58.11715.5461.0037.51 A
A

ATOM 691 C~2ASP 93 60.057 56.85617.2861.0032.16 A
A

ATCM 692 C ASP 93 61.948 56.79219.2831.0027.24 A
A

ATa'i O ASP 93 62.185 57.82719.8981.0028.92 A

ATOM 694 N t~J 94 61.072 55.87619.6981.0025.58 A
A

ATCM 695 C~ C31J 94 60.267 56.04820.9001.0025.65 A
A

ATOM 696 CB C3JU 94 59.246 57.16320.6751.0025.45 A
A

ATCM 697 CJ3Q.~J 94 58.558 57.65321.9251.0030.73 A
A

ATOM 698 CD C3~J 94 57.453 58.65621.6221.0033.86 A
A

ATCM 699 OEI.C3.~J 94 56.849 59.18022.5811.0037.23 A
A

ATCM 700 C~ C~J 94 57.185 58.91920.4301.0034.40 A
A

ATOM 701 C C~U 94 59.534 54.75021.2591.0024.95 A
A

ATOM 702 0 C3~U 94 59.256 53.90920.3911.0023.49 A
A

ATOM 703 N ALA 95 59.227 54.59622.5431.0022.68 A
A

ATCM 704 CA ALA 95 58.518 53.42423.0361.0021.32 A
A

ATCM 705 CB ALA 95 59.493 52.47323.6961.0019.75 A
A

ATCM 706 C ALA 95 57.438 53.84824.0331.0019.79 A
A

ATOM 707 O ALA 95 57.673 54.71024.8761.0020.35 A
A

ATOM 708 N ARG 96 56.257 53.25023.9191.0018.99 A
A

ATOM 709 CA ARG 96 55.135 53.54224.8111.0017.08 A
A

ATOM 710 CB ARG 96 54.140 54.50224.1521.0017.29 A
A

ATCM 711 C1~ARG 96 54.644 55.91223.9431.0019.86 A
A

ATOM 712 CD At~G 96 53.577 56.77223.2811.0020.48 A
A

ATOM 713 NE ARG 96 54.090 58.09722.9571.0020.05 A
A

A'nM 714 CZ AL~G 96 53.560 59.23623.3871.0020.06 A
A

ATE! 715 Ni1A1~ 96 52.481 59.22024.1661.0018.35 A
A

AnM 716 I~ Al~ 96 54.120 60.39323.0451.0018.71 A
A

A'iCM C ARG 96 54.387 52.25925.1501.0017.57 A

A'rCM O ARG 96 54.314 51.34524.3321.0017.71 A

AnM 719 N ~'YR 97 53.839 52.19626.3601.0017.91 A
A

A'1CM CA TYR 97 53.055 51.04526.7881.0017.62 A

P~ 72 CB TYR 97 52.810 51.07828.2931.0019.10 A

A'ICM C13'1'YR 97 54.036 50.95429.1501.0018.07 A

A'ICM Ca1TYR 97 54.422 51.98830.0071.0020.05 A

A'tCM CElTYR 97 55.533 51.85130.8471.0019.53 A

A'ICM CDe'ISZR 97 54.787 49.78429.1451.0018.33 A

AnM 726 CE2TYR 97 55.893 49.63629.9761.0021.62 A
A

A'ICM CZ TYR 97 56.260 50.66830.8211.0020.37 A

A'1rM CfiTYR 97 57.363 50.50431.6251.0024.62 A

A'ICM C TYR 97 51.712 51.21426.1101.0019.27 A

A'ICM O TYR 97 51.115 52.28826.1921.0019.79 A

A'ICr2 N HLS 98 51.220 50.18225.4401.0018.46 A

A'IC~! CA HIS 98 49.924 50.33124.8011.0019.79 A

AZCM 733 C8 HIS 98 49.882 49.60923.4431.0018.16 A
A

A'ICM OS HIS 98 49.965 48.11723.5361.0017.46 A

A'I~M CDeHIS 98 50.978 47.26223.2531.0013.73 A

A'IrM i~l.HIS 98 48.909 47.33623.9561.0015.85 A

A'ICM CE1HIS 98 49.269 46.06523.9271.0017.52 A

A'IC~i 1~2HIS 98 50.518 45.99323.503I.0015.37 A

A'ICM C HIS 98 48.836 49.81225.7331.0020.24 A

A'tCM O HIS 98 47.651 50.00925.4681.0021.54 A

A'rCM N ASP 99 49.244 49.17626.8341.0018.ll A

AnM 742 CA ASP 99 48.287 48.64427.7971.0019.54 A
A

A'ICM CB ASP 99 48.480 47.12627.9941.0016.57 A

l~ 744 (3;ASP 99 49.860 46.75828.5121.0017.16 A
A

A'ICM C~1ASP 99 50.080 45.55628.7821.0020.50 A

A'ICM OD2ASP 99 50.729 47.64528.6441.0017.05 A

A'ICM C ASP 99 48.287 49.34729.1561.0019.99 A

A'ICM 0 ASP 99 47.731 48.83930.1211.0022.65 A

ALCM 749 N ALA 100 48.895 50.52429.2361.0020.76 A
A

AnM 750 C~ ALA 100 48.913 51.27230.4911.0019.90 A
A

A'ICM CB ALA 100 50.245 51.98730.6651.0016. A

A'mM 752 C AL~1 100 47.779 52.28130.4021.0018.60 A
A

AZC~I O AIA 100 4?.604 52.92429.3671.0018.75 A

A'ICM N ASP 101 46.995 52.42231.4641.0016.75 A

AnM 755 CA ASP 101 45.890 53.37331.4111.0018.85 A
A

A'nM 756 CB ASP 101 44.669 52.72230.7501.0017.68 A
A

AICM 757 C~ ASP 101 43.499 53.68530.5921.0018.37 A
A

A'ILM C~1ASP 101 42.511 53.31029. 1.0019.00 A

AnM 759 CCdASP 101 43.557 54.81131.1311.0021.64 A
A

AnM 760 C ASP 101 45.478 53.98232.7481.0018.57 A
A

AnM 761 O ASP 101 44.796 53.35233.5521.0018.93 A
A

AnM 762 N VAL 102 45.896 55.22332.9661.0018.41 A
A

AnM 763 CA VAL 102 45.548 55.94934.1741.0018.19 A
A

AnM 764 CB VAL 102 46.795 56.24535.0261.0020.69 A
A

ALCM 765 (~lVAL 102 46.378 56.61736.4381.0022.37 A
A

A'nM 766 (~2VAL 102 47.702 55.03135.0541.0024.22 A
A

A'nM 767 C ZIAL 102 44.901 57.26033.7201.0016.96 A
A

AICM 768 O VAL 102 44.988 58.28134.4051.0015.50 A
A

ABM 769 N THIt 103 44.246 57.20832.5581.0016.32 A
A

AZCM 770 CA 'Iii 103 43.576 58.37131.9801.0016.74 A
A

A1CM 771 CB ~1R 103 42.912 58.03930.5941.0018.27 A
A

A'ICM OG1THIt 103 42.024 56.91830.7201.0015.47 A

AnM 773 C~2~iR 103 43.978 57.71029.5591.0015.60 A
A

A'ICM C ~t 103 42.521 58.89932.9371.0018.83 A

AnM 775 O g1R 103 42.213 60.09232.9431.0019.80 A
A

A'nM 776 N AtA 104 41.972 58.01733.7611.0018.62 A
A

A2CM 777 CA ALA 104 40.969 58.44434.7291.0020.45 A
A

AnM 778 CB ALA 104 40.517 57.26035.5731.0021.23 A
A

A1CM 779 C ALA 104 41.572 59.53735.6201.0021.91 A
A

AICM 780 O ALA 104 40.856 60.33136.2231.0022.43 A
A

A'ICM N P~ 105 42.896 59.57935.6981.0022.98 A

AnM 782 CA PHE 105 43.564 60.59536.5031.0024.90 A
A

AnM 783 CB PFD 105 44.667 59.95337.3431.0026.80 A
A

A'ICM C~ PFD 105 44.152 59.22038.5421.0028.7$ A

A1CM 785 CDlPfd 105 43.759 59.91839.6811.0031.57 A
A

AnM 786 CD2PFD 105 44.014 57.83838.5211.0027.93 A
A

A'nM 787 CElPI-~ 105 43.233 59.24440.7861 31 . .

A'IrM CE2Pig 105 43.490 57.15539.6161 29 . .

A'~~I CZ PFD 105 43.098 57.86040.7521.0029.27 A

A'ICM C PFD 105 44.134 61.74735.6771.0024.26 A

AnM 791 O Pfd 105 44.913 62.55536.1781.0026.06 A
A

A'ICriI N COY 106 43.744 61.82434.4101.0023.44 A

A2CM 793 CA GAY 106 44.229 62.90333.5661.0022.70 A
A

A'ICM C COY 106 45.567 62.65432.9011.0022.26 A

AnM 795 O COY 106 46.159 63.56832.3381.0023.24 A
A

A'1CM N TYR 107 46.064 61.42632.9701.0021.61 A

AnM 797 C~.TYR 107 47.330 61.10932,3271.0019.17 A
A

A'~I 798 CB TYR 107 48.007 59.92733.0121.0016.98 A
A

AnM 799 C~ 'IyR 107 48.488 60.26734.3861.0018.32 A
A

AEI 800 C171TYR 107 49.712 60.90634.5781.0019.00 A
A

A'ICM CE1TYR 107 50.117 61.29835.8551.0019.94 A

AnM 802 CC2TStR 107 47.683 60.02535.4971.0018.59 A
A

A'ICM CE2TYR 107 48.072 60.41236.766I.0018.47 A

ALCM 804 CZ TYR 107 49.286 61.04736.9401.0019.51 A
A

A'nM 805 CH TStR 107 49.648 61.43738.2061.0023.60 A
A

A'ICM C TYR 107 47.056 60.76130.8831.00I8.45 A

AnM 807 O TYR 107 45.957 60.34430.5371.0016.88 A
A

AnM 808 N (~J 108 48.058 60.94530.0371.0019.19 A
A

A'I~M CA C~J 108 47.910 60.61828.6351.0018.56 A

ALCM 810 C8 C~J 108 49.136 61.08927.8611.0018.58 A
A

ALCM 811 CG C~J 108 49.021 60.86826.3801.0019.46 A
A

AnM 812 Ca C~7 108 50.195 61.41925.6181.0016.80 A
A

A'ICM CALc~J 108 50.384 60.98824.4701.0022.81 A

AnM 814 C~2C3xJ 108 50.921 62.28426.1541.0018.35 A
A

ALCM 815 C (~J 108 47.792 59.10228.5561.0019.78 A
A

AnM 816 O C~J 108 48.376 58.39029.3671.0018.54 A
A

ALCM 817 N TYR 109 47.027 58.60227.5941.0021.88 A
A

AnM 818 C~ TYR 109 46.878 57.16227.4641.0022.78 A
A

A2LM 819 C8 TYR 109 45.978 56.81026.2781.0021.99 A
A

A'TC~2 CG TStR 109 45.706 55.33426.2241.0023.71 A

A1CM 821 CD1TStR 109 44.685 54.76526.9941.0023.77 A
A

A'ICM CE1T9tR 109 44.501 53.38227.0411.0021.93 A

AZrM 823 CCeTYR A 109 46.532 54.48425.4911.0022.66 A

ATOM 824 C~2TYR A 109 46.358 53.09925.5311.0023.55 A

A'ICM CZ TYR A 109 45.346 52.55626.3081.0022.61 A

A'I~M Qi TYR A 109 45.204 51.19026.3761.0024.09 A

ATOM 827 C TYR A 109 48.255 56.53227.2521.0022.10 A

AZt~2 O TYR A 109 49.072 57.06726.5041.0023.78 A

A'ICM N COY A 110 48.503 55.39627.8981.0021.85 A

A'nM 830 CA Q.Y A 110 49.785 54.72427.7561.0019.33 A

A'ICM C Q.Y A 110 50.810 55.20628.7691.0020.67 A

AnM 832 0 C3~Y A 51.803 54.52529.0451.0019.76 A

A'ICM N QN A 111 50.561 56.38529.3311. 19.20 A

A'1CM CA C3N A 111 51.455 56.97230.3161.0018.72 A

A'ICM C8 C3N A 111 51.362 58.50030.2641.0017.59 A

A'I~2 0~ QN A 111 52.118 59.21531.3841.0015.83 A

AnM 837 Ca QN A 111 51.926 60.72231.3401.0018.21 A

ABM 838 C~1C3N A 111 50.863 61.21330.9481.0017 .

A'nM 839 NE2C3N A 111 52.947 61.46431.7571.0015.01 A

ATOM 840 C QN A 111 51.161 56.51031.7371.0019.73 A

A2~M 841 O QN A 111 49.998 56.40532.1441.0016.99 A

AZrM 842 N L~7IJ A 52.225 56.23732.4851.0019.44 A

AnM 843 CA LFI1 A 52.095 55.83533.8791.0021.29 A

A'ICM CB LF11 A 52.938 54.59034.1621.0021.08 A

AZrM 845 03 LF~T A 52.279 53.32333.6051.0022.92 A

ALCM 846 CD1ICJ A 112 53.248 52.16533.5921.0022.01 A

ATOM 847 C~2L~J A 112 51.052 52.99634 1 23 . . .

ALCM $48 C LEx7 A 52.558 57.02134.7221.0022.07 A

A'ICM O LEZJ A 53.457 57.75834.3231.0022.55 A

A't~M N Hm A 113 51.937 57.22935.8921.0021.20 A

AnM 851 CD PRO A 113 50.863 56.41936.4911.0018.86 A

ATCM 852 CA PRO A 113 52.301 58.34436.7701.0022.92 A

A'ICM C8 PR0 A 113 51.443 58.09938.0121.0022.32 A

A'ICM C~ PRO A 113 50.235 57.39537.4461.0020.74 A

AnM 855 C PRO A 113 53.786 58.36937.0911.0024.77 A

A'ICM O PR0 A 113 54.370 57.33237.4001.0027.21 A

A1CM 857 N GLY A 114 54.391 59.55237.0151.0023.76 A

AnM 858 C~.C3rY A 55.809 59.67737.3101.0023.68 A

ALCM 859 C C3~Y A 56.698 59.38336.1131.0025.41 A

AlI.M O C3~Y A 57.923 59.48836.1981.0024.63 A

A'ICM N CYS A ll5 56.083 59.00634.9961.0023.61 A

ALCM 862 CA CYS A 115 56.828 58.70733.7751.0022.68 A

A'ICM C8 CYS A 115 56.557 57.28133.2901.0022.57 A

AnM 864 9G CYS A 115 57.012 55.95434.3711.0022.71 A

A'ICM C CYS A 115 56.368 59.61932.6581.0022.45 A

ALCM 866 O CYS A 115 55.242 60.10032.6641.0021.15 A

A1CM 867 N PRO A 116 57.245 59.88631.6871.0023.65 A

AnM 868 CD Pl~J A 58.690 59.60831.5911.0024.37 A

A1CM 869 CA PRO A 116 56.795 60.74330.5931.0022.64 A

ALCM 870 CB PRO A u6 58.095 61.07429.8621.0025.02 A

A'ICM 03 PR0 A 116 58.955 59.86530.1241.0025.08 A

AnM 872 C PRO A 116 55.852 59.85529.7691.0022.95 A

A'ICM O PRO A ll6 55.920 58.62829.8691.0023.14 A

AnM 874 N ALA A 117 54.967 60.45528.9791.0022.20 A

A''t~M C~1ALA A 117 54.027 59.67728.1721.0021.53 A

A'ICM C8 ALA A 117 53.222 60.61327.2681.0020.16 A

A'nM 877 C ALA A 117 54.754 58.62927.3271.0020.71 A

ALCM 878 O ALA A 117 54.237 57.54027.0771.0020.45 A

A'ICM N GLY A 118 55.955 58.97626.8852.0020.88 A

A'ICM C~.C3~Y A 56.746 58.07626.0741.0021.04 A

A'ICM C c~Y A 118 58.218 58.19726.4071.0022.34 A

A'ICM O c~.,Y A 58.667 59.20026.9661.0022.38 A

AnM 883 N P~ A 119 58.969 57.16126.0591.0022.99 A

AnM 884 CA 1~ A ll9 60.398 57.11326.3111.0023.97 A

ALCM 885 CB PIE A 119 60.740 55.80727.0181.0021.11 A

A'ICki OG Pfd A 119 60.001 55.61928.3081.0019.74 A

A'ICM CalPfd A ll9 60.491 56.16129.4911.0018.66 A

A'IrM CCdPfd A 119 58.808 54.91328.3401.0020.13 A

A'ICM CE1Pfd A 119 59.806 56.00230.6871.0015 .

Ate! 890 CE2PI~ A 119 58.111 54.74929.5331.0020.48 A

A'ICM CZ Pig A ll9 58.613 55.29530.7091.0017.86 A

A'ICM C Pfd A 119 61.1ll 57 24 1. 23 . 59 892 , . 00 A

AnM 893 O Pies A 60.936 56.35024.1051.0023.29 A

A'IrM N LYS A 120 61.911 58.24724.8081.0023.70 A

A'ICM C~1LYS A 120 62.620 58.46423.5631.0025.47 A

A'I~M C8 LYS A 120 62.864 59.96423.3681.0028.21 A

A'ICM O LYS A 120 61. 60. 23 1. 33 . 87 897 ; 580 765 .183 00 A

A'ICM CO LYS A 120 61.854 62.25423.0651.0039.73 A

AEI 899 CE LY5 A 120 60.568 63.03022.7971.0044.80 A

AnM 900 1~ LYS A 120 60.810 64.49822.6561.0046.14 A

A'~2 901 C LYS A 120 63.930 57.70523.4301.0024.61 A

A'ICM O LYS A 120 64.757 57.69424.3431.0025.00 A

ATOM 903 N ALA A 121 64.106 57.06322.2811.0023.20 A

ATOM 904 CA ALA A 121 65.330 56.32922.0121.0025.31 A

ATOM 905 C8 ALA A 121 65.146 55.39720.8131.0023.30 A

ATOM 906 C ALA A 121 66.414 57.36421.7281.0024.60 A

ATOM 907 0 ALA A 121 66.120 58.50021.3661.0024.92 A

ATOM 908 N ASP A 122 67.666 56.96021.9071.0025.6 8 A

ATOM 909 CA ASP A 122 68.814 57.83021.6971.0024.57 A

ATOM 910 CB ASP A 122 70.050 57.15322.2811.0024.63 A

ATOM 911 Os ASP A 122 71.256 58.04622.2841.0023.32 A

ATOM 912 C~1ASP A 122 71.315 58.95323.1371.0023.90 A

ATLM 913 OD2ASP A 122 72.144 57.84121.4341.0026.82 A

ATOM 914 C ASP A 122 69.044 58.13020.2141.0024.44 A

ATOM 915 O ASP A 122 69.101 57.21619.4041.0024.43 A

ATOM 916 N ASP A 123 69.188 59.41019.8701.0026.96 A

ATOM 917 CA ASP A 123 69.419 59.83118.4841.0028.63 A

ATOM 918 CB ASP A 123 69.585 61.35018.4141.0030.$7 A

ATOM 919 CJ3ASP A 123 68.274 62.09218.5721.0035.89 A

ATOM 920 C~1ASP A 123 68.316 63.27018.9861.0040.10 A

ATOM 921 C~12ASP A 123 67.203 61.51618.2741.0035.82 A

ATOM 922 C ASP A 123 70.646 59.17817.8571.0029.63 A

ATOM 923 O ASP A 123 70.600 58.71816.7161.0028.81 A

ATOM 924 N Ix5 A 124 71.748 59.14618.5971.0030.56 A

ATOM 925 CA LYS A 124 72.969 58.54718.0751.0032.60 A

A'PCM CB LYS A 124 74.103 58.63$19.1051.0034.62 A

A'nM 927 C~ LxS A 124 74.309 60.01919.7071.0040.41 A

ATOM 928 CD LYS A 124 74.702 61.04318.6581.0043.72 A

ATOM 929 CE LYS A 124 74.918 62.42319.2761.0047.18 A

A'ICM NZ LYS A 124 76.045 62.45120.2591.0047.59 A

ATOM 931 C LYS A 124 72.709 57.07917.7421.0031.67 A

ATCM 932 O LYS A 124 73.007 56.61216.6401.0031.00 A

ATCM 933 N LFIJ A 72.146 56.35118.7001.0029.76 A

AT<M 934 CA LF~J A 71.874 54.93918.4871.0028.11 A

ATOM 935 C8 ICJ A 125 71.281 54.32019.7541.0026.17 A

ATCM 936 (~ LF~J A 72.153 54,42421.0121.0027.71 A

ATCM 937 CfllLFIT A 71.460 53.73822.1801.0028.43 A

ATOM 938 CD2LExJ A 73.509 53.78720.7591.0026.17 A

ATCM 939 C LEIJ A 70.948 54.71817.2951.0027.71 A

ATCM 940 O LQJ A 125 71.168 53.81616.4891.0028.21 A

ATCM 941 N a E A 126 69.915 55.54517.1811.0028.45 A

ATOM 942 CA aE A 126 68.970 55.42016.0791.0028.49 A

ATCM 943 CB ILE A 126 67.836 56.45016.1981.0026.92 A

ATOM 944 C02II~E A 66.943 56.37614.9691.0028.36 A

AT;M 945 031T1~E A 67.030 56.19917.4781.0026.15 A

ATOM 946 CD1ILE A 126 66.033 57.30317.8021.0021.29 A

ATCM 947 C ILE A 126 69.674 55.63414.7431.0029.25 A

ATOM 948 O ILE A 126 69.495 54.85913.8001.0028.89 A

ATQK 949 N ALA A 127 70.472 56.69614.6721.0030.83 A

ATOM 950 CA ALA A 127 71.205 57.02513.4551.0031.70 A

ATOM 951 CB ALA A 127 72.006 58.31113.6561.0030.74 A

ATCM 952 C ALA A 127 72.137 55.87913.0851.0031.92 A

AT~I 953 O ALA A 127 72.221 55.48011.9201.0032.45 A

ATOM 954 N AIA A 128 72.837 55.35114.0831.0031.22 A

ATOM 955 CA ALA A 128 73.755 54.24813.8551.0029.82 A

AIM 956 C8 ALA A 128 74.360 53.80015.1681.0031.25 A

A'nM 957 C ALA A 128 72.981 53.10313.2141.0030.52 A

ATOM 958 O ALA A 128 73.388 52.56212.1811.0029.21 A

A'nM 959 N ALA A 129 71.857 52.75013.8321.0028.44 A

AnM 960 CA ALA A 129 71.007 51.67413.3471.0028.53 A

ATOM 961 C8 ALA A 129 69.795 51.52414.2561.0027.97 A

A'I~M C ALA A 129 70.554 51.89911.9081.0027.80 A

AZrM 963 0 ALA A 129 70.553 50.97511.1131.0027.18 A

ATrM 964 N Gu1 A 130 70.151 53.12211.5831.0030.17 A

ATOM 965 CA CST A 130 69.702 53.44110.2231.0034.37 A

ATCM 966 CB C3,L1 A 69.158 54.87710.1501.0035.61 A

ATOM 967 O3 (~U A 130 68.034 55.19411.1361.0040.12 A

A'nM 968 CD C3~IJ A 66.640 55.07910.5381.0042.29 A

AnM 969 ~1 C3zJ A 66.291 54.0119.986 1.0044.58 A

AZrM 970 C~2C~J A 130 65.876 56.06710.6261.0044.09 A

AZrM 971 C C3~1 A 70.896 53.3059.271 1.0034.37 A

A'ICM O t~JU A 70.731 52.9978.087 2.0036.11 A

AnM 973 N ALA A 131 72.096 53.5409.794 1.0034.92 A

ATOM 974 C2~ALA A 131 73.307 53.4218.988 1.0035.70 A

ALCM 975 C8 ALA A 131 74.508 53.9539.761 1.0036.52 A

ATOM 976 C ALA A 131 73.526 51.9548.623 1.0036.13 A

A2LM 977 O ALA A 131 73.818 51.6247.470 1.0037.28 A

A'ICM N CYS A 132 73.388 51.0739.609 1.0033.89 A

ATOM 979 CA CYS A 132 73.557 49.6489.369 1.0034.13 A

A'nM 980 C8 CYS A 132 73.401 48.86610.6741.0033.79 A

AnM 981 93 CYS A 132 74.708 49.16311.8861.0032.37 A

ATrM 982 C CYS A 132 72.509 49.1868.366 1.0034.53 A

A'IrM O CYS A 132 72.806 48.4457.433 1.0034.82 A

ABM 984 N ILE A 133 71.279 49.6398.573 1.0035.01 A

A'ICM C~.ILE A 133 70.161 49.3007.705 1.0035.41 A

AnM 986 CB ~E A 133 68.899 50.0678.146 1.0034.47 A

A2CM 987 CG2ILE A 133 67.856 50.0387.050 1.0035.29 A

A'ICM 0311LE A 133 68.375 49.4699.459 1.0035.77 A

A'ICM CD1~E A 133 67.333 50.30810.1571.0031.59 A

A'ICM C IZ,E A 70.474 49.6186.243 1.0036.35 A

ATCM 991 O ILE A 133 70.209 48.8115.353 1.0035.50 A

ATCM 992 N ALA A 134 71.037 50.7976.001 1.0037.06 A

A'ICM CA ALA A 134 71.380 51.1974.645 1.0040.15 A

AEI 994 CB ALA A 134 71.815 52.6604.620 1.0039.77 A

AZCM 995 C ALA A 134 72.496 50.3094.108 1.0041.16 A

A'IC~'t O ALA A 134 72.400 49.7772.999 1.0042.44 A

AZC~I N C~J A 2,3573.543 50.1424.910 1.0041.67 A

A~22 998 CA C3~U A 74.694 49.3314.531 1.0042.83 A

AnM 999 CB C~7lJ A 75.759 49.3965.626 1.0044.78 A

ALCM 1000O~ C~IJ A 76.285 50.7975.885 1.0046.63 A

ATCM 1001CD (~JIJ A 77.370 50.8266.943 1.0047.98 A

AnM 1002 Cpl.C3~IJ A 77.846 51.9337.274 1.0048.10 A

AnM 1003 CE2C~J A 135 77.749 49.7437.441 1.0049.57 A

AnM 1004 C C~J A 135 74.349 47.8744.247 1.0042.44 A

AnM 1005 O C~.7U A 74.987 47.2283.410 1.0042.55 A

AnM 1006 N L~7 A 136 73.345 47.3544.945 1.0041.28 A

ABM 1007 CA LFLT A 72.934 45.9664.763 1.0039.42 A

A'IC~2 C8 IFIJ A 72.450 45.3856.094 1.0038.29 A

ABM 1009 C~ IExJ A 73.539 45.2347.159 1.0038.52 A

ALCM 1010CalL~J A 136 72.921 44.8248.483 1.0037.85 A

AnM 1011 CD2LExJ A 74.552 44.1946.703 1.0037.90 A

ALCM 1012C LE~J A 71.842 45.8463.707 1.0038.85 A

AnM 1013 O LE~J A 71.437 44.7433.343 1.0038.62 A

AEI 1014 N ASt~i A 71.369 46.9903.224 1.0039.18 A

ABM 1015 C~.A3d A 137 70.331 47.0392.200 1.0040.34 A

ABM 1016 CB ASfiT A 70.870 46.4490.893 1.0042.23 A

A'ICM 03 A~1 A 137 69.881 46.561-0.2461.0044.61 A

ALCM 1018C9~1AS~T A 69.353 47.640-0.5191.0047.17 A

ATCM 1019I~ ACT A 137 69.624 45.447-0.9221.0046.27 A

AnM 1020 C A~1 A 137 69.052 46.3132.622 1.0040.17 A

A'1~M O ASrT A 68.444 45.5831.835 1.0040.37 A

A'.t~t N LaU A 138 68.640 46.5283.866 1.0038.75 A

A'ICM G~1ICJ A 138 67.440 45.8964.397 1.0036.62 A

A'ICM C8 I~T A 138 67.692 45.4055.825 1.0035.62 A

A'ICNI OJ I~7 A L38 68.845 44.4326.089 1.0035.31 A

A'I~M ~1 I~7U A 68.993 44.2227.595 1.0033.16 A

A'1CM CD2LF7U A 68.587 43.1095.390 1.0032.37 A

ABM 1028 C L~1 A 138 66.298 46.8974.414 1.0036.57 A

A'ICM O I~T A 138 66.530 48.1024.444 1.0037.81 A

ALCM 1030N ASt~1 A 65,065 46.4054.383 1.0036.11 A

A'I~M CA ASN A 139 63.913 47.2974.443 1.0037.04 A

A'IGM C8 A~1 A 139 62.671 46.6603.815 1.0038.40 A

A'ICM CG ASST A 61.473 47.6023.814 1.0041.87 A

A'iCM OD1AS~T A 60.322 47.1653.868 1.0045.29 A

A'ICM ND2AgT A 139 61.739 48.9023.740 1.0043.07 A

ATOM 1036C ASl~1 63.664 47.5055.929 1.0036.84 A
A
7.39 ATOM 1037O ASD1 139 63.689 46.5486.705 1.0036.68 A
A

ATCM 1038N ALA 140 63.427 48.7466.328 1.0037.07 A
A

ATLM 1039CA ALA 140 63.194 49.0427.733 1.0036.18 A
A

ATOM 1040CB ALA 140 64.523 49.2358.455 1.0035.15 A
A

ATOM 1041C ALp. 140 62.337 50.2787.899 1.0036.02 A
A

ATCM 1042O ALA 140 62.165 51.0676.967 1.0037.23 A
A

AT~I 1043N tTAL 141 61.799 50.4399.099 1.0034.97 A
A

ATCM 1044CA UAL 141 60.962 51.5819.410 1.0032.49 A
A

ATCM 1045C8 VAL 141 59.467 51.2029.368 1.0032.27 A
A

ATCM 1046C~1VAL 141 58.611 52.4299.620 1.0032.13 A
A

ATCM 1047OG2VAL 141 59.128 50.5778.021 1.0032.85 A
A

ATOM 1048C UAL 141 61.316 52.06910.8061.0032.48 A
A

AT~I 10490 UAL 141 61.535 51.26811.7221.0032.39 A
A

ATOM 1050N ARG 142 62.393 53.38610.9562.0030.62 A
A

ATOHI CA A~ 142 61.703 53.98712.2381.0030.71 A

ATOM 1052CB ARG 142 62.789 55.04612.0951.0032.18 A
A

ATOM 1053O; ARG 142 63.304 55.53713.4241.0038.01 A
A

A~.CM CD A1~G 142 63.480 57.04013.4101.0043.71 A

ATOM 1055NE ARG 142 64.396 57.47812.3621.0045.60 A
A

ATOM 1056CZ ARG 142 64.710 58.75012.1401.0048.25 A
A

ATOM 10571~HLARG 142 64.180 59.70412.8931.0049.65 A
A

ATOM 10581~ ARG 142 65.557 59.07011.1701.0049.80 A
A

ATOM 1059C ARG 142 60.440 54.64112.7701.0029.80 A
A

ATOM 1060O Alit 142 59.651 55.20012.0081.0029.20 A
A

ATOM 1061N C3~Y 143 60.249 54.57614.0811.0026.67 A
A

A'nM 1062CA C3~Y 143 59.068 55.17714.6561.0022.75 A
A

ATOM 1063C GAY 143 58.723 54.60616.0111.0022.30 A
A

A'nM 1064O COY 143 59.546 53.95716.6591.0020.86 A
A

A'ICM N IaJ 144 57.485 54.85016.4241.0021.06 A

A'ICM CA L~7U 144 56.976 54.40417.7131.0021.33 A

AnM 1067 CB IEx1 144 55.671 55.13918.0401.0019.46 A
A

A'1~CM O~ L~3J 144 54.890 54.59819.2441.0018.27 A

AnM 1069 CD1I~1 144 55.671 54.85420.5171.0016.09 A
A

AZrM 1070C~t2L~J 144 53.524 55.25919.3101.0015.65 A
A

ATC,M C ICI 144 56.722 52.91417.8141.0021.00 A

ATOM 1072O I~7U 144 56.050 52.33316.9661.0023.09 A
A

ATOM 1073N ~E 145 57.272 52.29918.8551.0020.84 A
A

A'ICM CA ILE 145 57.045 50.88319.1101.0019.76 A

A'ICNt CB ILE 145 58.358 50.08719.1781.0019.30 A

A'ICM ~2 ILE 145 58 . 48 19 1. 18 . 58 107 6 A 086 . . 00 A

A'ICM CALItrE 145 58.985 50.01417.7761.0022.53 A

ATOM 1078CD1IIE 145 60.251 49.17717.6881.0022.14 A
A

A'ICM C ICE 145 56.309 50.78420.4461.0020.98 A

ATOM 1080O ~.,E 145 56.722 51.39121.4411.0020.07 A
A

A'ICM N UAL 146 55.214 50.03120.4671.0020.26 A

AIC~2 CA VAL 146 54.432 49.88321.6861.0019.34 A

A'nM 1083C8 UAL 146 52.955 50.22921.4291.0020.13 A
A

A'ICM C~1VAL 146 52.840 51.70021.0121.0018.94 A

AZrM 1085C~2VAL 146 52.383 49.31720.3471.0020.30 A
A

A'ICM C VAL 146 54.528 48.49522.3151.0019.20 A

ATOM 1087O UAL 146 54.575 47.48621.6131.0019.85 A
A

A'hCM N gR 147 54.559 48.45723.6461.0017.30 A

A'ICM CA Sat 147 54.664 47.19624.3761.0017.00 A

AZC~I CB SE~t 147 55.943 47.16925.2171.0014.57 A

ALCM 1091OG SEIt 147 57.059 47.60024.4691.0018.00 A
A

AnM 1092 C Sat 147 53.482 46.96425.3011.0017.70 A
A

ALCM 10930 SER 147 52.826 47.90425.7481.0018.31 A
A

ATCM 1094N C3~Y 148 53.233 45.69425.5971.0018.84 A
A

ATCM 1095CA (~Y 14$ 52.150 45.31426.4861.0018.29 A
A

A'ICM C GLY 148 52.386 43.87626.8981.0019.22 A

AIC~i 0 C3~Y 148 53.249 43.21426.3191.0018.37 A

ALCM 1098N ASP 149 51.649 43.38227.8891.0019.47 A
A

AnM 1099 CA ASP 149 51.830 41.99828.3021.0021.17 A
A

A'ICM C8 ASP 149 51.701 41.85029.8171.0019.58 A

ALCM 110103 ASP 149 53.005 42.ll130.5211.0022.08 A
A

AEI 1102 OD1ASP 149 54.050 42.06029.8351.0020.56 A
A

A~i 1103 OD2ASP 149 52.992 42.35731.7441.0020.28 A
A

A'ICM C ASP 149 50.889 41.02527.6081.0021.73 A

AnM 1105 O ASP 149 50.458 40.03028.1981.0021.73 A
A

AnM 1106 N ALA 150 50 . 41. 26. 1. 22 . 0 A'ICM CA Aid. 150 49.708 40.44025.5661.0022.51 A

AnM 1108 C8 ALA 150 48.307 41.04725.4961.0021.99 A
A

ALCM 1109C ALA 150 50.241 40.20324.1571.0023.58 A
A

AnM 1110 O ALA 150 50.765 41.11523.5181.0022.44 A
A

A'ICM N Pig 151 50.119 38.96923.6791.0024.59 A

A'ICM C~1Pfd 151 50.555 38.66022.3281.0025.76 A

A'ICM C8 H~ 151 50.865 37.17522.1751.0025.51 A

A'nM 1114Q~iPHE 151 51.303 36.79820.7891.0026.87 A
A

A'ICM Cn1PIE 151 50.379 36.35319.8481.0026.35 A

AnM 1116 Ci~Pfd A 151 52.634 36.92620.4091.0026.06 A

A'1CM CAL1~ A 151 50.772 36.04518.5521.0024.87 A

ALCM 1118CE2Pfd A 151 53.039 36.62019.1111.0025.38 A

A'ICM CZ PIE A 151 52.104 36.17918.1811.0026.93 A

A'nM 1120C PIE A 151 49.410 39.05421.4101.0026.23 A

ALCM 1121O Pfd A 151 48.373 38.39921.3891.0027.73 A

ALCM 1122N II~E A 49.601 40.13820.6641.0027.46 A

A'ICM CA 7ZE A 152 48.573 40.64919.7641.0027.85 A

ALCM 1124CB B.~E A 48.990 42.01519.2071.0027.35 A

ABM 1125 C~2~E A 152 47.808 42.68518.5161.0025.00 A

A'nM 1126CAL~E A 152 49.506 42.89020.3531.0025.99 A

A'I~M CD1~E A 152 48.515 43.07021,4871.0021.76 A

AnM 1128 C ~E A 152 48.314 39.67118.6241.0029.65 A

A'ICM O ~E A 152 49.230 39.29517.8881.0030.39 A

A'ICM N A,~1 A 47.054 39.27318.4811.0030.76 A

A'ICM CA ACT A 153 46.658 38.29917.4691.0032.19 A

AZCM 1132CB ASST A 46.449 36.94418.1581.0035.21 A

A1CM 1133C~ ASN A 153 46.307 35.79817.1831.0037.56 A

A'I~M OD1A9rT A 46.109 34.65417.5861.0039.69 A

ATOM 1135I~.12ASI~T A 46.410 36.09515.8971.0040.35 A

A'ICM C .~4V A 45.379 38.71716.7471.0032.45 A

A~C'M O ASTT A 44.424 37.94516.6681.0032.64 A

AnM 1138 N GZY A 154 45.369 39.93716.2211.0031.86 A

ALCM 1139C~.COY A 154 44.202 40.43715.5181.0033.01 A

AnM ll40 C GZY A 154 43.064 40.79716.4561.0035.47 A

AnM 1141 O COY A 154 43.283 41.13617.6251.0035.91 A

ABM 1142 N Sat 41.842 40.73415.9361.0034.91 A
A

AnM 1143 CA SER 155 40.647 41.03416.7181.0035.80 A
A

ALCM 1144CB Sat 155 40.442 39.93717.7711.0036.15 A
A

AnM 1145 OG S~ 155 39.175 40.03518.4011.0040.46 A
A

A'ICM C Sat 155 40.707 42.41517.3861.0035.07 A

ATCM 1147O SE~2 155 41.244 43.36716.8191.0035.34 A
A

A'nM 1148N UAL 156 40.152 42.51118.5901.0033.16 A
A

AnM 1149 CA UAL 156 40.119 43.76219.3431.0032.18 A
A

AnM 1150 CB VAL 156 39.089 43.65720.5011.0034.03 A
A

A'tCM C7G1.VAL 156 39.291 42.35521.2521.0036.16 A

ALCM 1152C~2UAL 156 39.223 44.84221.4501.0035.09 A
A

AnM 1153 C VAL 156 41.489 44.18719.8921.0029.61 A
A

A'nM 1154O VAL 156 41.759 45.37720.0471.0029.14 A
A

AnM 1155 N COY 157 42.351 43.21920.1841.0028.31 A
A

A~2 1156 CA COY 157 43.667 43.55420.6941.0024.87 A
A

AnM 1157 C Q~Y 157 44.390 44.49419.7451.0024.05 A
A

ABM 1158 O c~Y 157 44.919 45.52620.1551.0022.99 A
A

ALCM 1159N LExT 158 44.398 44.13318.4651.0023.14 A
A

A'ICM CA LET 158 45.058 44.91417.4321.0023.95 A

A'PCM CB LET 158 45.156 44.08716.1481.0024.67 A

AnM 1162 C~ L~J 158 45.715 44.77814.9051.0025.40 A
A

A'ICM CD1LE~J 158 47.150 45.23415.1591.0024.82 A

AnM 1164 CD2LBJ 158 45.647 43.81113.7251.0023.53 A
A

A'ICM C LF11 158 44.366 46.24017.1321.0025.32 A

AnM 1166 O LQJ 158 45.010 47.29117.1091.0024.95 A
A

AnM 1167 N ALA 159 43.054 46.19316.9091.0025.75 A
A

A'.tCM CA ALA 159 42.284 47.39716.5871.0026.40 A

A'ICM C8 ALA 159 40.804 47.03816.4221.0024.68 A

A'ICM C ALA 159 42.442 48.50117.6321.0027.13 A

AnM 1171 O ALA 159 42.593 49.67617.2951.0029.12 A
A

AnM 1172 N Lx5 160 42.393 48.12218.9031.0028.12 A
A

AZCM 1173CA LYS 160 42.533 49.07819.9971.0027.17 A
A

A'nM 1174CB LYS 160 42.411 48.33721.3341.0029.23 A
A

ALCM ll7 00 LYS 160 42.470 49.20822.5871.0030.37 A
A

A'ICM C~ LYS 160 42.258 48.34323.8341.0033.83 A

AEI 1177 CE LYS 160 42.407 49.13825.1261.0037.64 A
A

ABM 1178 NZ LYS 160 42.280 48.25626.3241.0040.32 A
A

AZCM 1179C LYS 160 43.889 49.77319.8951.0026.62 A
A

A'nM 1180O LYS 160 43.996 50.99120.0591.0024.34 A
A

A'IrM N ~E 161 44.924 48.98719.6201.0026.45 A

A'nM 1182CA ~E 161 46.269 49.51919.4951.0027.55 A
A

AnM 1183 CB ~ 161 47.288 48.37719.3351.0027.09 A
A

AnM 1184 C~ aE 161 48.653 48.93118.9991.0028.90 A
A

A'ICM CG1aE 161 47.350 47.56920.6321.0028.62 A

A'nM 1186CD1~E 161 48.263 46.38020.5761.0026.09 A
A

A1C.M C ~E 161 46.357 50.47618.3111.0027.93 A

ATCM 1188O ~E 161 46.882 51.58618.4431.0 27.46 A

AnM ll89 N ARG 162 45.835 50.05617.1611.0028.19 A
A

A'ICM CA Ate 162 45.862 50.90115.9641.0029.31 A

A'nM ll91B Al~ 162 45.256 50.16914.7621.0027.65 A
A

ATCM 1192O;~A~ 162 46.125 49.06314.2001.0028.59 A
A

A~.CM CD ARG 162 45.520 48.48912.9271.0029.41 A

A'ICM NE ARG 162 46.289 47.35412.4271.0030.89 A

ATOM 1195CZ APG 162 47.479 47.45111.8411.0029.55 A
A

ATtM 1196NH1ARG 162 48.041 48.63511.6731.0029.90 A
A

ATrM 1197I~lA~G 162 48.106 46.35911.4241.0031.70 A
A

ATOM 1198C ARG 162 45.098 52.19916.1991.0029.33 A
A

A'ICM O ARG 162 45.449 53.23815.6531.0028.99 A

AT'M 1200N HIS 163 44.050 52.13317.0131.0029.41 A
A

ATOM 1201CA HIS 163 43.253 53.31117.3181.0030.19 A
A

A'ICM CB HLS 163 41.894 52.88317.8821.0033.90 A

ATCM 1203C~ HIS 163 41.068 54.01618,4091.0038.46 A
A

ATCM 1204C~ HLS 163 40.107 54.76917.8211.0040.47 A
A

AT<M 1205ND1HIS 163 41.184 54.48519.7011.0040.70 A
A

ATCM 1206CE1.HIS 163 40.328 55.47519.8871.0041.27 A
A

ATCM 1207NE2HIS 163 39.662 55.66718.7621.0042.07 A
A

AICM 1208C HIS 163 43.967 54.24118.3001.0028.62 A
A

A~~2 1209O HIS 163 44.005 55.45018.0941.0029.16 A
A

ATCM 1210N As~i 164 44.538 53.68019.3601.0026.52 A
A

A'PCM CA ASf1 164 45.237 54.48920.3561.0025.85 A

ATLM 1212CB ASr1 164 45.448 53.68621.6411.0026.98 A
A

A'ICM O3 A3~T 164 44.184 53.57622.4791.0029.15 A

A'TCM OD1ASr1 164 43.985 52.59523.1931.0030.13 A

AT<M 1215I~ ASr1 164 43.335 54.59222.4081.0027.13 A
A

AT'M 1216C ACT 164 46.580 55.02019.8691.0024.29 A
A

ATOM 1217O .~1 164 46.994 56.11720.2411.0024.91 A
A

AnM 1218 N PFD 165 47.259 54.24619.0331.0023.16 A
A

ATOM 1219CA PHS 165 48.558 54.66218.5221.0023.04 A
A

A'nM 1220CB PHE 165 49.673 53.87019.2201.0021.92 A
A

ATOM 1221C~ PIE 165 49.622 53.94620.7261.0021.49 A
A

A'ICM C~11Pfd 165 48.809 53.08321.4531.0019.96 A

A'IrM C~ PIE 165 50.376 54.89721.4131.0020.17 A

A'ICM CALPFD 165 48.744 53.16022.8511.0020.81 A

A'IrM CE2PIE 165 50.321 54.98722.8051.0020.63 A

A'ICM CZ Pfd 165 49.501 54.11323.5281.0021.02 A

AnM 1227 C PIE 165 48.614 54.44217.0191.0023.97 A
A

A'ICM O Pig 165 49.295 53.53616.5361.0023.70 A

ALCM 1229N PRO 166 47.896 55.27816.2551.0025.12 A
A

AnM 1230 CD PRO 166 47.152 56.46916.6921.0025.29 A
A

A'ICM CA PRO 166 47.871 55.15814.7961.0026.95 A

A'ICM C8 PRO 166 46.941 56.29614.3711.0026.62 A

A'IrM Os PRO 166 47.156 57.31515.4401.0028.62 A

AnM 1234 C PRO 166 49.248 55.24714.1521.0027.70 A
A

ATOM 1235O PR0 166 49.439 54.76213.0451.0029.57 A
A

A'ICM N CAN 167 50.211 55.84514.8481.0027.37 A

A'1CM CA QN 167 51.564 55.97614.2911.0028.98 A

A'I~CM C8 C~:N 167 52.211 57.29514.7471.0029.38 A

AnM 1239 C~ CAN 167 52.581 57.35816.2571.0032.89 A
A

ALCM 1240CD C3N 167 51.371 57.50017.1611.0032.55 A
A

A'ICM OE1.QN 167 50.431 56.72917.0711.0034.27 A

A'ICM I~2QN 167 51.396 58.48918.0431.0036.65 A

ATCM 1243C Q.N 167 52.501 54.81314.6511.0029.24 A
A

AICM 1244O C3N 167 53.614 54.72814.1241.0030.91 A
A

AnM 1245 N ALA 168 52.056 53.92015.5391.0027.80 A
A

A'ILM CA ALA 168 52.883 52.78815.9561.0024.71 A

ALCM 1247C8 ALA 168 52.140 51.95616.9831.0024.79 A
A

A'ICM C Aid 168 53.280 51.91714.7691.00 26.16 A'~M 12490 ALA 168 52.426 51.54213.9531.00 26.11 A A

A'ICM N ILE 169 54.568 51.58114.6771.00 23.22 A'IC~i C?~ ~E 169 55.057 50.75413.5741.00 23.20 AT'M 1252CB IIE 169 56.450 51.22313.0811.00 22.77 A A

A'ICM C~2 ILE 169 56.389 52.69812.7081.00 20.06 A'IC~I 031 ~E 169 57.501 50.97014.1691.00 21.84 A'ICM CD1 ILE 169 58.914 51.35413.7811.00 21.59 A'ICM C ILE 169 55.165 49.27313.9311.00 23.17 AEI 1257 O ILE 169 55.222 48.41913.0401.00 22.78 A A

A'ICM N ALA 170 55.202 48.97115.2271.00 20.79 A'ICM CA ALA 170 55.318 47.58615.6791.00 19.31 A'IrM C8 ALA 170 56.761 47.09915.5231.00 17.01 AEI 1261 C ALA 170 54.868 47.41417.1271.00 19.11 A A

A'ICI~t O ALA 170 54.852 48.37317.9061.00 16.79 AZCM 1263N UAL 171 54.506 46.18017.4721.00 16.88 A A

AT'M 1264CA UAL 171 54.061 45.85318.8151.00 17.64 A A

AnM 1265 C8 UAL 171 52.530 45.61418.8621.00 18.03 A A

AICM 1266CG1 VAL 171 52.141 44.53117.8531.00 17.54 A A

AnM 1267 032 VAL 171 52.102 45.21420.2761.00 17.90 A A

ATOM 1268C VAL 171 54.768 44.59819.3001.00 19.39 A A

ATOM 1269O VAL 171 54.966 43.64418.5461.00 21.24 A A

A'ICM N C~J 172 55.165 44.61220.5631.00 19.07 A'ICM CA CPU 172 55.836 43.47321.1611.00 18.47 A'ICM C8 C~J 172 57.312 43.45720.7511.00 19.23 AT3~2 O,~ C3.~J172 57.959 44.81620.7271.00 21.59 AT3~t CD Q.~J172 58.110 45.38122.1161.00 23.74 ATOM 1275C~1 C~J 172 57.404 46.36122.4451.00 22.41 A A

AZCM 1276C~2 CPU 172 58.934 44.83022.8761.00 24.83 A A

A'ICM C C~T 172 55.633 43.51522.6761.00 17.26 ATOM 1278O C~J 172 54.686 44.14823.1371.00 16.50 A A

A'IrM N 1~T 173 56.502 42.87723.4581.00 18.08 AnM 1280 CA 1~'I'173 56.269 42.82324.9071.00 16.86 A A

ATCM 1281CB MET 173 55.793 41.40525.2651.00 16.16 A A

A'ICM C~ MET 173 54.562 40.92524.4821.00 15.89 AnM 1283 SD MET 173 54.164 39.15924.6881.00 20.55 A A

ATOM 1284CE MET 173 53.806 39.07126.4571.00 19.68 A A

ATCM 1285C MET 173 57.356 43.23525.9101.00 18.05 A A

A'ICM O I~,'I'173 57.176 43.01727.1151.00 19.13 ATOM 1287N C~U 174 58.466 43.82325.4601.00 17.13 A A

ATCM 1288CA CPU 174 59.515 44.21026.4081.00 17.86 A A

A'ICM CB C~J 174 60.665 43.18826.3831.00 16.74 ATCM 1290C~ C31J174 60.261 41.76126.7431.00 15.74 A A

AZCM 1291CD CPU 174 59.739 40.97625.5501.00 16.09 A A

AZrM 1292C~1 CPU 174 58.993 39.99825 1 14 . . .

P:nM 1293DE2 C~U 174 60.084 41.33024.4021.00 19.90 A A

ATOM 1294C CPU 174 60.108 45.60726.2241.00 19.12 A A

ATCM 1295O C3~U174 60.518 46.24927.1961.00 20.53 A A

ATCM 1296N ALA 175 60.148 46.06224.9761.00 18.89 A A

ATOM 1297CA ALA 175 60.721 47.35324.6071.00 19.34 A A

ATt,M CB ALA 175 60.230 47.74023.2211.00 18.48 ATOM 1299C ALA 175 60.508 48.51825.5741.00 19.04 A A

ATOM 1300O ALA 175 61.470 49.09226.0941.00 20.57 A A

ATOM 1301N ~ 176 59.255 48.86625.8261.00 19.03 A A

ATOM 1302CPS 'IHR176 58.960 49.99226.7061.00 19.29 A A

ATCM 1303CB Ti-~t176 57.461 50.33826.6671.00 20.77 A A

ATOM 1304OG1 THR 176 57.011 50.35825.3061.00 19.55 A A

A'I~M 032 'IHR176 57.223 51.69827.2981.00 18.08 ATOM 1306C THR 176 59.382 49.77328.1581.00 18.96 A A

ATOM 1307O ~ 176 59.704 50.72928.8591.00 19.54 A A

A'~I 1308N ALA 177 59.375 48.52228.6071.00 17.93 A A

ATOM 1309CA ALA 177 59.768 48.20229.9741.00 17.80 A A

A'I~M CB ALA 177 59.484 46.75030.2711.00 15.81 ATOM 1311C ALA 177 61.256 48.47830.0991.00 19.49 A A

ATCM 13120 ALA 177 61.724 49.02331.1011.00 20.51 A A

ATOM 1313N ILE 178 61.995 48.09829.0641.00 18.59 A A

A'ICM CA ILE 178 63.431 48.30929.0361.00 18.18 ATCM 1315C8 llrE178 64.052 47.57227.8311.00 18.99 A A

ATOM 1316Ou2 ILE 178 65.513 47.97027.6561.00 18.33 A A

A'ICM 03L ILE 178 63.888 46.06128.0351.00 17.12 ATOM 1318CD1 ILE 178 64.371 45.21726.8751.00 18.18 A A

ATOM 1319C ILE 178 63.712 49.80928.9561.00 18.63 A A

AT~I 1320O ILE 178 64.558 50.32429.6821.00 17.37 A A

AT~I 1321N ALA 179 62.991 50.49928.0721.00 17.93 A A

ATOM 1322CA ALA 179 63.141 51.94527.9021.00 17.45 A A

AT~I 1323CB ALA 179 62.165 52.45026.8271.00 13.72 A A

AT~I 1324C ALA 179 62.849 52.63829.2331.00 17.81 A A

AT~I 1325O ALA 179 63.566 53.54429.6561.00 19.02 A A

AT~I 1326N HIS 180 61.782 52.19729.8831.00 17.82 A A

ATOM 1327CA HIS 180 61.366 52.74831.1681.00 18.38 A A

A'ICM CB F~.S180 60.130 51.98231.641 1.0019.34 A

A'nM 1329~ FMS 180 59.519 52.50232.903 1.0019.79 A
A

A'IL~2 CD2 FMS 180 60.037 53.23533.918 1.0020,90 A

ABM 1331 I~1 FMS 180 58.219 52.21733.260 1.0020.66 A
A

AICM 1332C~1 HIS 180 57.962 52.75034.442 1.0021,33 A
A

ABM 1333 I~2 Fff,S180 59.048 53 34 1 20 A

. . . .

A'ICM C FMS 180 62 . 52 32 .1911. 17 A
1334 A S05 . 00 .

A'nM 1335O FUSS180 62.853 53 32.835 1.0017.16 A
A .646 ALCM 1336N UAL 181 63.085 51.46432.335 1.0017.71 A
A

AIC~t CA UAL 181 64.184 51.26133.279 1.0016.80 A

AnM 1338 C8 UAL 181 64.567 49.77033.367 1.0016.30 A
A

AICM 1339031 UAL 181 65.815 49.59334.222 1.0015,31 A
A

AICM 1340OG2 VAL 181 63.406 48.97633.955 1.0014.90 A
A

AnM 1341 C UAL 181 65.414 52.08932.900 1.0018.27 A
A

A'ICM O UAL 181 66.064 52.67133.764 1.0018.10 A

A'IC~i N CYS 182 65.726 52.14331.606 1.0018.86 A

APCM 1344CA CYS 182 66.865 52.91531.119 1.0018.58 A
A

A'ICM CB CYS 182 67.061 52.68429.620 1.0017.97 A

A'I~t 9G CYS 182 67.678 51.03929.223 1.0019.14 A

A'ICM C CYS 182 66.637 54.39531.391 1.0020.68 A

A'ICM O CYS 182 67.566 55.12931.747 1.0021.76 A

A'ICM N FMS 183 65.395 54.83631.226 1.0021.05 A

A'ICM CA F~.S183 65.056 56.22731.476 1.0021.07 A

A'iCM CB FO:S183 63.569 56.46531.253 1.0021.24 A

A'ICM CG HIS 183 63.116 57.83531.647 1.0021.36 A

A'ICM C~ FMS 183 62.446 58.27232.739 1.0022.91 A

ATOM 1354ND1 183 63.372 58.95230.8831.00 23.08 HIS A
A

AT'M 1355CE1 HIS 183 62.881 60.01931.4871.00 22.49 A A

ATCM 1356NE2 HIS 183 62.314 59.63432.6161.00 22.12 A A

AT'M 1357C HIS 183 65.392 56.55732.9311.00 21.53 A A

ATOM 1358O HLS 183 66.050 57.55933.2131.00 20.38 A A

AT<M 1359N ASn1184 64.937 55.70233.8461.00 21.39 A A

ATCM 1360CA AST1184 65.164 55.90935.2731.00 22.47 A A

ATCM 1361CB ASST184 64.425 54.85736.1041.00 23.08 A A

ATCM 1362OS ASS 184 62.926 55.08836.1401.00 26.1 5 A A

ATOM 1363~1 A3~1184 62.231 54.55037.0011.00 29.94 A A

ATCM 13641~2 ASr1184 62.417 55.88035.2011.00 24.77 A A

ATCM 1365C A3~1184 66.630 55.90335.6531.00 22.47 A A

AT<M 1366O AS~1184 67.014 56.50636.6511.00 24.34 A A

A'ICM N Pi-~185 67.445 55.20534.8751.00 22.70 ATCM 1368CA PFD 185 68.873 55.16335.1471.00 24.60 A A

ATCM 1369C~ Pfd 185 69.412 53.73535.0141.00 24.90 A A

A'IrM C'G Pfd 185 69.089 52.86336.1911.00 26.36 AT'M 1371C~1 PHA 185 68.016 51.98336.1511.00 25.87 A A

A'ICM C~2 PHS 185 69.837 52.95737.3651.00 28.51 ATOM 1373CE1 PHE 185 67.689 51.20937.2571.00 26.36 A A

ATCM 1374CE2 Pfd 185 69.518 52.18838.4791.00 28.86 A A

AT<M 1375CZ PHE 185 68.441 51.31238.4251.00 28.79 A A

ATCM 1376C Pfd 185 69.637 56.10134.2281.00 23.90 A A

ATOM 1377O PFD 185 70.858 56.19534.3061.00 24.63 A A

A'I~I N ACT 186 68.904 56.79833.3631.00 25.35 ATOM 1379CA AS~1186 69.493 57,74432.4221.00 26.27 A A

ATOM 1380CB A3~T186 70.219 58.85933.1841.00 31.83 A A

A'mM 138103 ASr1186 70.739 59.95332.2671.0035.93 A A

AICM 1382OD1 ACT 186 71.644 60.69932.6361.0040.34 A A

A'ICM I~2 A~1 186 70.164 60.05831.0701.0038.18 A'ICM C ACT 186 70.465 57.05031.4681.0024.77 A'IC~2 O A~1 186 71.525 57.58931.1431.0023.91 A'ICM N VAL 187 70.095 55.85631.0201.0022.45 A2CM 1387CA VAL 187 70.924 55.08930.0991.0023.22 A A

A'ICM C8 UAL 187 71.071 53.62330.5861.0025.07 A'ICM CG1 UAL 187 71.783 52.78729.5341.0023.79 A'ICM CG2 VAL 187 71.848 53.58831.9051.0022.88 AnM 1391 C VAL 187 70.328 55.09028.6871.0022.93 A A

A'ICM 0 UAL 187 69.173 54.72328.4931.0021.85 A''ICM N PRO 188 71.110 55.52327.6841.0023.34 AICM 1394~ PRO 188 72.453 56.13127.7881.0023.13 A A

AZC~I CA E~RO188 70.624 55.55626.3011.0022.49 A'I~2 CB PRO 188 71.831 56.08025.5181.0024.08 A'nM 13970~ PRO 188 72.540 56.95126.5221.0022.61 A A

A'ICM C Am 188 70.206 54.17025.8191.0023.59 A'nM 1399O P1~ 188 70.883 53.17826.0981.0023.07 A A

A~C'M N PHE 189 69.096 54.10325.0901.0021.99 A'IC~ CA PIE 189 68.628 52.83124.5671.0022.40 AIC~I C8 PFD 189 67.488 52.27825.4211.0023.16 A'I~I C~ PFD 189 66.166 52.92625.1401.0022.88 A'ICM CD1 Pfd 189 65.829 54.13425.7301.0023.85 A'I~t ~ Pig 189 65.287 52.36024.2261.0024.25 AnM 1406 C~'1Pfd 189 64.635 54.77425.4121.0020.76 A A

A2CM 1407CE2 Pfd A 64.089 52.99123.8981.00 22.72 A'I~i CZ PFD A 63.765 54.20124.4941.00 23.95 A'I~I C Pfd A 68.109 52.97823.1441.00 22.60 A'nM 1410O PHE A 67.880 54.08022.6561.00 22.37 A'nM 1411N VAL A 67.925 51.84122.4891.00 22.28 A'~2 1412CA VAL A 67.370 51.79621.1491.00 20.06 A(C~t CB VAL A 68.411 52.08920.0421.00 20.93 ALCM 1414O~. VAL A 69.388 50.93219.9041.00 19.20 A'ICM CG2 VAL A 67.689 52.32818.7201.00 22.23 A2CM 1416C UAL A 66.840 50,38820.9701.00 20.54 A'iCM O UAL A 67.442 49.41821.4481.00 18.66 A'ICM N UAL A 65.697 50.28320.3061.00 20.16 A'ICM CA VAL A 65.087 48.99620.0561.00 20.03 A'ICM C8 VAL A 63.587 49.02520.4071.00 20.94 ALCM 1421O~. VAL A 62.969 47.65520.1761.00 17.99 A'ICM CJG2VAL A 63.406 49.46321.8661.00 18.71 A'ICM C UAL A 65.267 48.67418.5811.00 22.25 AICM 1424O VAL A 64.942 49.48317.7151.00 23.09 A'IC~ N UAL A 65.826 47.50218.3041.00 23.96 A'ICM CA DIAL A 66.042 47.06116.9351.00 23.70 ALCM 1427C~ VAL A 67.537 47.08016.5561.00 24.55 AICM 142803.1UAL A 67.714 46.60015.1171.00 25.32 A'ICM C.~2VAL A 68.095 48.47816.7181.00 22.09 A'ICM C VAL A 65.524 45.64016.8261.00 23.07 AICM 1431O VAL A 66.216 44.68817.1771.00 25.43 AIC~ 1432N ARG A 64.297 45.50016.3451.00 21.80 AnM 1433 CA ARG A 63.690 44.18516.2181.00 22.47 ATOM 1434CB ARG A 62.431 44.11917.0881.00 20.64 AnM 1435 C~ ARG A 62.721 44.05818.5891.00 21.59 ATCM 1436CD ARG A 61.479 44.37419.4171.00 21.52 ATOM 1437NE ARG A 61.731 44.33520.8581.00 18.31 ATOM 1438CZ ARG A 61.391 43.32521.6491.00 16.72 ATOM 1439Nii1ARG A 60.783 42.26421.1451.00 19.32 ALCM 14401~ ARG A 61.659 43.37422.9461.00 19.73 A'ICM C ARG A 63.353 43.83214.7741.00 22.14 A2CM 1442O ARG A 63.342 44.69213.8971.00 21.58 ATCM 1443N ALA A 63.095 42.55314.5311.00 22.97 ATOM 1444CA ALA A 62.746 42.09713.1941.00 24.10 ATCM 1445C8 ALA A 63.694 41.00412.7411.00 24.83 ATOM 1446C ALA A 61.322 41.57713.2221.00 23.33 ATOM 1447O ALA A 60.896 40.95014.1851.00 23.02 ATCM 1448N ILE A 60.586 41.84212.1571.00 24.83 ATOM 1449CA ILE A 59.206 41.41212.0761.00 24.28 AT'M 1450CB III A 58.501 42.11810.9051.00 24.35 ATOM 1451C7G2I<E A 57.055 41.66910.8101.00 22.06 ATCM 1452C~1 ICE A 58.594 43.63511.1031.00 23.13 ATCM 1453CD1 ILE A 58.159 44.10012.4961.00 24.46 ATOM 1454C ILE A 59.060 39.89911.9361.00 25.76 ATCM 14550 ILE A 59.722 39.26311.1071.00 24.27 ATOM 1456N SEft A 58.192 39.33212.7691.00 24.53 ATOM 1457CA SEi~ A 57.928 37.90212.7531.00 23.24 ATOM 1458C8 SEit A 58.253 37.29514.1171.00 23.55 ATOM 1459OG SER A 57.354 37,77615.1031.00 23.68 ATOM 1460C ~ A 196 56.457 37.64112.4281.00 23.57 A

A'~M 14610 Sat A 56.062 36.50312.191 1.0025.42 A

ALCM 1462N ASP A 55.652 38.69912.418 1.0024.10 A

A2CM 1463CA ASP A 54.221 38.58212.150 1.0024.34 A

AnM 1464 CB ASP A 53.537 37.83713.300 1.0025.34 A

ALCM 1465OG ASP A 53.717 38.54614.638 1.0026.63 A

A1CM 1466C~1.ASP A 52.964 39.49914.927 1.0024.05 A

A'TCM c~2 ASP A 54.636 38.16315.390 1.0026.98 A

AnM 1468 C ASP A 53.640 39.98312.049 1.0025.55 A

AnM 1469 0 ASP A 54.303 40.95812.390 1.0026.68 A

A2CM 1470N UAL A 52.404 40.08511.580 1.0027.11 A

A'IC~i CA VAL A 51.753 41.38111.460 1.0028.26 A

A'ICM CB VAL A 51.149 41.58410.052 1.0028.12 A

AfiCM CJG1.UAL A 52.263 41.7499 1 29 A

. . .

A2~M 1474C~2 UAL A 50.277 40.3949.677 1.0029.83 A

AiCM 1475C VAL A 50.663 41.51312.516 1.0028.17 A

A'nM 1476O VAL A 49.699 42.25512.348 1.0028.37 A

ALCM 1477N ALA A 50.832 40.77013.606 1.0030.03 A

ALCM 1478CA ALA A 49.908 40.79614.735 1.0031.31 A

A'ICM CB ALA A 50.129 42.07415.533 1.0031.84 A

A1CM 1480C ALA A 48.425 40.66114.389 1.0032.49 A

A'ICM 0 ALA A 47.5$2 41.24715.063 1.0030.79 A

AZCM 1482N ASP A 48.105 39.89713.348 1.0034.59 A

A'ICM C?~ ASP A 46.710 39.70012.964 1.0036.41 A

A'nM 1484CS ASP A 46.536 39.88211.451 1.0036.03 A

AnM 1485 C~ ASP A 47.321 38.86510.641 1.0035.15 A

A'IrM OD1 ASP A 47.323 38.9769.397 1.0037.51 A

A'nM 1487C7D2AS's 200 47.933 37.95811.237 1.0035.45 A
A

AnM 1488 C ASP 200 46.268 38.30313.384 1.0037.72 A
A

A'ICM 0 ASP 200 46.972 37.63014.136 1.0037.49 A

ALCM 1490N QN 201 45.109 37.87012.893 1.0039.23 A
A

AnM 1491 CA QN 201 44.565 36.55013.215 1.0041.47 A
A

A'1CM C$ QN 201 43.400 36.21412.280 1.0044.43 A

AnM 1493 C~ QN 201 42.152 37.05112.476 1.0050.84 A
A

AICM 1494CD QN 201 41.031 36.64711.528 1.0053.22 A
A

A'ICM DEL C3N 201 39.936 37.21111.564 1.0055.88 A

AnM 1496 NE2 QN 201 41.304 35.66610.670 1.0053.88 A
A

A'nM 1497C QN 201 45.570 35.39613.153 1.0040.36 A
A

A'I~M O Q.N 201 45.465 34.43713.921 1.0038.75 A

A'ICM N Q'.N 202 46.529 35.47712.236 1.0040.27 A

ALCM 1500CA QN 202 47.518 34.41212.085 1.0042.39 A
A

A'nM 1501CB C~.N 202 47.723 34.08810.603 1.0046.89 A
A

A'nM 150203 Q1V 202 46.484 33.5969.871 1.0051.03 A
A

ABM 1503 CD C3N 202 46.809 33.0828.480 1.0053.67 A
A

A'nM 1504DE:LQN 202 47.322 33 7 1 55 A

. . . .

A'nM 1505NE2 Ql1 202 46.519 31.8088.238 1.0055.88 A
A

P:ICM C C3N 202 48.881 34.70912.701 1.0040.87 A

A'ICM O QN 202 49.856 34.02212.397 1.0041.07 A

A'I~2 N 5'ER 203 48.957 35.71513.565 1.0038.12 A

A'I~M CA gR 203 50.234 36.07014.170 1.0036.51 A

AZCM 1510CB SER 203 50.060 37.25515.132 1.0036.93 A
A

AGM 1511 OG SER 203 49.226 36.92716.229 1.0033.96 A
A

A'ICM C S~3t 203 50.897 34.89914.894 1.0036.66 A

A'ICM O gR 203 52.121 34.79414.915 1.0035.50 A

ALCM 152 N HIS 204 50.092 34.01615.4791.0036.67 A
A

A'IrM C~.HIS 204 50.619 32.86116.1961.0036.72 A

A'ICM C8 HIS 204 49.491 32.14216.9371.0039.49 A

ALCM 1517C1~HLS 204 49.873 30.78817.4521.0042.97 A
A

A'IrM C~ HIS 204 49.378 29.55817.1761.0045.48 A

AnM 1519 1~1HLS 204 50.895 30.59418.3561.0045.55 A
A

A'nM 1520CALHLS 204 51.013 29.30318.6161.0045.69 A
A

A~Q~I 1~2HIS 204 50.104 28.65317.9121.0045.85 A

A'ICM C HLS 204 51.344 31.87015.2791.0037.41 A

A'nM 1523O HIS 204 52.458 31.43515.5841.0036.97 A
A

AIOM 1524N LD~J 205 50.710 31.49914.1691.0037.10 A
A

A'nM 1525CA L~~J 205 51.325 30.56113.2311.0037.77 A
A

A'ICM CB L'E71'J205 50.303 30.06712.2001.0039.06 A

A'ICM C~ LFIT 205 49.281 29.01012.6391.0039.41 A

A'trM CD1LF1J 205 48.474 29.48913.8411.0041.70 A

A'ICM c~2LE~U 205 48.356 28.71911.4741.0041.61 A

A''tOM C L~7U 205 52 . 31. 12 1. 37 . 50 153 0 A 495 229 . 00 A

A'ICM 0 LF1T 205 53.542 30.61312.3181.0037.92 A

AnM 1532 N S~Ft 206 52.319 32.49212.1461.0036.47 A
A

ABM 1533 CA SER 206 53.391 33.22811.4801.0035.61 A
A

A'nM 1534CB SE~t 206 52.938 34.65011.1461.0035.18 A
A

.F.~~ OG S~t 206 53.996 35.38810.5591.0035.96 A

A'ICM C S'ER 206 54.590 33.27912.4191.0034.95 A

A'ICM O SFR 206 55.721 33.00212.0181.0034.80 A

A'I~I N PFD 207 54.326 33.63413.6741.0034.24 A

A'I~I CA P~ 207 55.359 33.71214.6961.0032.66 A

ATLM 1540CB P~ 207 54.726 33.96416.0641.0032.37 A
A

ATCM 1541CG Pig 207 55.722 34.20017.1641.0031.87 A
A

ATCM 1542C~ H~ 207 56.306 35.45517.3351.0030.49 A
A

A'ICM C~ Pty 207 56 . 33 18 1. 31.10 A
1543 A 068 .172 . 0 ATLM 1544CELPig 207 57.218 35.68618.3691.0030.31 A
A

A'ICM CE2Pfd 207 56.980 33.39019.0781.0032.34 A

ATCM 1546CZ PI~ 207 57.556 34.65219.2441.0029.84 A
A

ATCM 1547C I~ 207 56.118 32.39214.7291.0033.85 A
A

ATCM 1548O PIE 207 57.345 32.37414.6801.0033.51 A
A

ATOM 1549N ASP 208 55.377 31.28814.8031.0035.54 A
A

AT'M 1550CA ASP 208 55.979 29.95714.8561.0038.71 A
A

A'nM 1551CB ASP 208 54.906 28.88215.0471.0040.28 A
A

ATCM 1552CG ASP 208 54.338 28.85916.4521.0042.14 A
A

A'ICM C~1ASP 208 55.104 29.07517.4161.0041.08 A

ATCM 1554~2 ASP 208 53.125 28.60416.5911.0043.72 A
A

ATCM 1555C ASP 208 56.803 29.58813.6281.0040.06 A
A

ATLM 1556O ASP 208 57.801 28.87413.7321.0040.65 A
A

ATCM 1557N C31U 209 56.385 30.07112.4661.0040.59 A
A

AT~I 1558CA C~J 209 57.080 29.74811.2311.0042.89 A
A

AICM 1559CB C~J 209 56.076 29.71210.0741.0044.61 A
A

ATCM 1560C~ C~fJ 209 54.975 28.66710.2541.0048.38 A
A

ATiM 1561CD C~J 209 53.798 28.8729.313 1.0050.37 A
A

AT'M 1562Cue(.CST 209 52.866 28.0389.339 1.0051.66 A
A

A'ICM ~2 C3.~J209 53.799 29.8668.553 1.0051.76 A

ATOM 1564C C~J 209 58.233 30.68210.8841.0042.32 A
A

ATiM 1565O CST 209 59.213 30.25210.2861.0043.25 A
A

ATCM 1566N Pfd 210 58.135 31.95111.2621.0041.75 A
A

A'1rM C~1PIE 210 59.192 32.89410.9251.0041.36 A

A~ 1568 C8 Pfd 210 58.621 34.04710.1021.0040.45 A
A

A'iCM C~ PHE 210 57.841 33.6058.905 1.0042.31 A

A'ICM CfllPHE 210 56.450 33.5828.936 1.0041.50 A

ALCM 1571CD2P~ 210 58.495 33.1937.746 1.0042.46 A
A

A'ICM CALPFD 210 55.721 33.1557.827 1.0042.80 A

A'ICM CE2PFD 210 57.776 32.7646.634 1.0040.84 A

A2CM 1574CZ PFD 210 56.388 32.7446.674 1.0042.56 A
A

AnM 1575 C E3~ 210 59.976 33.47312.0911.0040.84 A
A

A'ICM O Pfd 210 60.672 34.46911.9231.0041.71 A

A'iCM N L~J 211 59.872 32.87313.2711.0040.56 A

AZC~t cue.LF~J 211 60.616 33.39614.4101.0039.30 A

A'I~i CS LFiT 211 60.322 32.58715.6741.0038.57 A

A'ICM 03 L~1 211 61.087 33.04216.9231.0038.49 A

ALCM 1581c~ L~1 2ll 60.821 34.52217.1691.0037.52 A
A

A'ICM ClrlLB1 211 60.668 32.20318.1251.0036.51 A

A'ICM C LEx1 211 62.097 33.31114.0771.0038.81 A

ALCM 1584O LE~IJ211 62.871 34.21114.3961.0038.71 A
A

A'ICM N ALA 212 62.474 32.22013.4191.0038.44 A

ABM 1586 C~ ALA 212 63.857 31.99013.0231.0038.81 A
A

A'tCM CB ALA 212 63.965 30.66512.2701.0039.05 A

A'ICM C ALA 212 64.404 33.12512.1621.0038.75 A

ALCM 15890 ALA 212 65.457 33.69112.4631.0040.24 A
A

A'nM 1590N VAL 213 63.688 33.46411.0951.0037.44 A
A

AnM 1591 (~.VAL 213 64.138 34.52910.2091.0036.58 A
A

AnM 1592 CB VAL 213 63.206 34.6828.975 1.0037.12 A
A

A'IC1~2 0~1UAL 213 62.979 33.3218.329 1.0036.72 A

A'ICM Q~ VAL 213 61.885 35.3219.374 1.0037.86 A

A'ICM C UAL 213 64.212 35.85110.9581.0035.49 A

AnM 1596 0 VAL 213 65.091 36.67210.7021.0036.52 A
A

A'ICM N ALA 214 63.282 36.05811.8831.0034.36 A

A'ICM CA ALA 214 63.274 37.28312.6641.0033.08 A

A2CM 1599CB ALA 214 62.039 37.33413.5511.0032.35 A
A

AnM 1600 C ALA 214 64.539 37.29613.5111.0031.90 A
A

AZCM 1601O ALA 214 65.233 38.30513.5911.0033.08 A
A

A'ICM N ALA 215 64.841 36.15914.1301.0032.43 A

AnM 1603 CA ALA 215 66.028 36.03614.9731.0032.99 A
A

AnM 1604 C8 ALA 215 66.072 34.65315.6141.0032.21 A
A

A'LL~I C ALA 215 67.287 36.26414.1461.0032.35 A

A'ICM O ALA 215 68.237 36.89314.5991.0031.50 A

A1CM 1607N LYS 216 67.279 35.74412.9261.0032.71 A
A

A1CM 1608C~ LYS 216 68.414 35.87812.0311.0033.16 A
A

A'ICM C8 IyS 216 68.151 35.07310.7581.0035.75 A

A~NI 1610OG LY5 216 69.369 34.8509.885 1.0040.45 A
A

A'nM 1611CD LYS 216 69.078 33.8148.807 1.0042.79 A
A

ABM 1612 CE LYS 216 70.304 33.5447.942 1.0047.19 A
A

A1CM 1613NZ LYS 216 70.088 32.4236.966 1.0049.74 A
A

AZCM 1614C LxS 216 68.656 37.34711.6951.0032.46 A
A

AnM 1615 O LStS 216 69.756 37.86411.8901.0032.39 A
A

An,M 1616N C3N 217 67.617 38.02211.2131.0031.59 A
A

AnM 1617 CA C31~T217 67.724 39.42610.8391.0031.55 A
A

ABM 1618 CB f~N 217 66.474 39.85810.0821.0032.71 A
A

A'nM 161903 (3N 217 66.307 39.1578.743 1.0034.69 A
A

A'ICM CD QN 217 67.569 39.2167.898 1.0035.70 A

A'tCM DELQN 217 68.350 38.2637.856 1 36 A

. .

AnM 1622 NE2C3N 217 67.784 40.3457.237 1.0035.00 A
A

A'ICM C CST 217 67.980 40.38212.0061.0031.02 A

ALCM 1624O CAN 217 68.754 41.32611.8731.0031.11 A
A

A~i 1625 N SER 218 67.334 40.15513.1421.0029.67 A
A

A'I~2 CA S'E~Et218 67.560 41.02814.2921.0029.34 A

A'iCM CB Sit 218 66.576 40.70915.4191.0028.20 A

A''LCM OG S'E~.t218 66.690 39.35815,8281.0027.71 A

A'ICM C SER 218 68.994 40.84414.7861.0029.67 A

A'ICM 0 SEI~t218 69.690 41.82115.0641.0029.55 A

AICM 1631N S'E~2219 69.433 39.59014.8781.0029.57 A
A

A'ICM CA SEIt 219 70.785 39.28515.3351.0032.43 A

A'ICM C8 SER 219 70.999 37.76715.4221.0034.18 A

ABM 1634 OG Sit 219 70.999 37.17014.1321.0038.93 A
A

AnM 1635 C SF~t 219 71.812 39.90014.3891.0032.88 A
A

AnM 1636 O S~R 219 72.827 40.43814.8301.0033.14 A
A

ATCM 1637N L~J 220 71.544 39.81913.0891.0032.97 A
A

A'ICM CA LET 220 72.441 40.39312.0891.0033.76 A

AICM 1639C8 LFZ1 220 71.887 40.16010.6761.0034.76 A
A

A'ICM CJ~LFZJ 220 72.598 40.8589.512 1.0037.26 A

A'ICM CD1LFI1 220 74.017 40.3249.3?3 1.0036.05 A

A'tCM CD2ICJ 220 71. 40 8 .2191. 36. A
1642 A 816 . 0 88 ABM 1643 C LExJ 220 72.574 41.89112.3401.0032.08 A
A

P~ 1644 O LE~J 220 73.676 42.43212.3491.0032.69 A
A

A'ICM N 1~.'I'221 71.441 42.55712.5391.0030.61 A

A'ICM CA 1~,'I'221 71.435 43.99312.7931.0029.70 A

A'ICM CB MET A 221 70.001 44.51212.8861.0028.94 A

AnM 1648 CG 1~T A 221 69.396 44.94711.5621.0030.14 A

AnM 1649 SD NET A 221 70.280 46.33610.8331.0031.05 A

A'ICM CE MET A 221 69.944 47.65312.0271.0028.08 A

ALCM 1651C NET A 221 72.181 44.33914.0761.0029.94 A

AEI 1652 O I~T A 221 ?3.005 45.24414.0941.0031.45 A

A'ICM N UAL A 222 71.888 43.62415.1561.0029.58 A

A'PCM CA UAL A 222 72.561 43.89816.4131.0029.91 A

A'ICM C8 VAL A 222 72.095 42.94117.5231.0028.74 A

A'ICM C1~1.VAL A 222 72.995 43.08018.7391.0028.05 A

A'ICM O~ VAL A 222 70.658 43.25917.8981.0028.58 A

A'nM 1658C VAL A 222 74.068 43.77616.2451.0030.06 A

AICM 1659O VAL A 222 74.813 44.67316.6321.0030.57 A

AnM 1660 N (~J A 223 74.514 42.66515.6661.0031.48 A

A'ICM CA C3~J A 75.939 42.44515.4511.0033.24 A

A'ICM CB C~J A 223 76.177 41.16514.6431.0035.98 A

AZC~2 C~ C31T A 75.589 39.90715.2611.0040.45 A

AnM 1664 CD C~J A 223 75.688 38.70014.3371.0043.83 A

A'nM 1665C~1C3~T A 74.882 37.75414.4981.0044.88 A

ALCM 1666~2 C~J A 223 76.577 38.69613.4571.0044.57 A

AnM 1667 C C~U A 223 76.508 43.62814.6921.0031.98 A

A~2 1668 O C~J A 223 77.596 44.10214.9971.0033.57 A

AT(M 1669N S~t A 224 75.758 44.10413.7021.0031.76 A

ABM 1670 CA SE~t A 76.180 45.24112.8921.0030.96 A

A~ICM CB SEFt A 75.278 45.36911.6651.0032.65 A

AnM 1672 OG SE~t A 75.322 44.18810.8771.0035.46 A

ATCM 1673C S~Tt A 76.159 46.55013.6801.0030.70 A

ATCM 1674O SF3t A 77.047 47.38813.5341.0031.20 A

ATOM 1675N TAT A 225 75.142 46.72514.5151.0029.64 A

A'ICM CA L~'J A 75.029 47.93815.3121.0030.09 A

ATrM 1677CB ICJ A 225 73.680 47.96816.0341.0027.91 A

ATCM 1678C.1;~L~J A 225 73.331 49.25216.7961.0028.59 A

ATCM 1679CD1LBJ A 225 73.480 50.46215.8851.0023.42 A

A'nM 1680C~ L~J A 225 ?1.900 49.14917.3271.0026.74 A

ATOM 1681C IF~J A 76.171 48.03316.3251.0030.30 A

ATrM 1682O LF~T A 76.753 49.10016.5221.0031.34 A

A'nM 1683N VAL A 226 76.488 46.91716.9711.0031.92 A

AIrM 1684CA VAL A 226 77.566 46.90717.9451.0033.07 A

ATrM 1685C8 VAL A 226 77.769 45.50818.5461.0031.16 A

ATOM 1686CJ~1VAL A 226 79.013 45.49019.4241.0028.27 A

ATOM 1687r.X~2vAL A 226 76.549 45.12419.3671.0030.75 A

A'ITM C VAL A 226 78.845 47.34617.2501.0035.40 A

ATLM 1689O VAL A 226 79.567 48.21017.7471.0036.60 A

AEI 1690 N QN A 227 79.109 46.76016.0881.0037.40 A

ATCM 1691CA QN A 227 80.302 47.09415.3281.0039.53 A

ATfl~2 C8 GIN A 227 80.343 46.29614.0251.0042.52 A

ATtM 1693Os C3N A 227 81.483 46.69613.0961.0045.77 A

A'ICM CD QN A 227 82.852 46.36913.6671.0048.98 A

ATCM 1695CALC3N A 227 83.874 46.88213.1981.0049.11 A

A'ICM N~2C3N A 227 82.881 45.50414.6791.0048.23 A

A'nM 1697C QN A 227 80.352 48.58315.0101.0040.35 A

A'ICM O QN A 227 81.346 49.25115.2901.0040.76 A

A'ICM N LYS A 228 79.274 49.10014.4311.0039.98 A

A'ICM CA LYS A 228 79.217 50.50714.0651.0041.35 A

A'IC~t G8 LYS A 228 77.944 50.79613.2661.0042.00 A

ALCM 1702(3;LYS A 228 77.845 52.2361.2.7921.0043.42 A

A'nM 1703~ LYS A 228 76.795 52.39411.7081.0045.84 A

A'ICi2 CE LYS A 228 77.134 51.54610.4$01.0047.56 A

A'nM 1705NZ LYS A 228 78.475 51.8739.916 1.0046.87 A

ALCM 1706C LXS A 228 79.304 51.46115.2511.0041.64 A

A'nM 1707O LYS A 228 79.877 52.54015.1371.0041.36 A

A'nM 1708N ICJ A 229 78.734 51.07516.3871.0042.29 A

A'ICM CA LET A 229 78.781 51.93117.5661.0044.16 A

AnM 1710 CB LBT A 229 77.806 51.43418.6371.0043.24 A

ALCM 1711C1SIE~J A 76.321 51.73218.4571.0041.94 A

A'nM 1712CD1LEiJ A 75.554 51.15919.6371.0039.73 A

ABM 1713 CD2LFII A 76.106 53.23418.3601.0039.53 A

A'ICNt C IF~J A 80 .18151.97718.1611.0045.42 A

A'iCM O LExJ A 80.618 53.00918.6711.0045.74 A

A'1~CM N ALA A 230 80.877 50.84818.0891.0046.54 A

A'ICM CA ALA A 230 82.218 50.73218.6411.0048.3 4 AICM 1718C~ ALA A 230 82.564 49.26118.8441.0049.11 A

AnM 1719 C ALA A 230 83.279 51.39417.7801.0048.72 A

A'tCM O ALA A 230 84.285 51.88118.2911.0048.85 A

A'i~M N FMS A 231 83.056 51.41716.4731.0050.25 A

A'ICM CA HIS A 231 84.026 52.00815.5711.0052.17 A

AnM 1723 CB I~,S A 84.707 50.88714.7871.0053.72 A

A'IC~t ~ I-aS A 85.185 49.76715.6581.0055.04 A

A'ICM C1~HIS A 231 84.865 48.45115.6791.0056.09 A

A'ICM 1~E1 86.065 49.96216.7031.0056.12 A

A

ATOM 1727CELHIS 231 86.262 48.81717.3321.0055.73 A
A

ATCM 17281~2HIS 231 85.545 47.88416.7311.0056.66 A
A

AT<M 1729C HIS 231 83.399 53.03714.6411.0053.29 A
A

ATLM 1730O HIS 231 83.191 54.18715.0341.0054.08 A
A

AT<M 1731N Q.Y 232 83.094 52.63213.4141.0053,85 A
A

A'I~M CA C~Y 232 82.493 53.56012.4751.0054.28 A

ATOM 1733C C3~Y 232 81.590 52.88611.4641.0054.39 A
A

ATCM 1734O GLY 232 81.435 51.64911.5351.0054.49 A
A

AATOM Qxi'C31Y 232 81.036 53.59810.5981.0055.77 A

ATOM 1736C8 MET 1 64.319 38.76860.4141.0042.52 B
B

A'ICM C~ I~,T 1 63.234 39.49761.1891.0046.66 B

AT'M 1738SD NB,T 1 61.611 38.71960.9861.0054.35 B
B

A'ICM CB MET 1 61.597 37.59362.3931.0051.82 B

A'I?CM C MET 1 65.426 40.91659.8291.0036.68 B

A'nM 1741O MEi' 1 65.347 41.87560.5971.0036.12 B
B

ATiM 1742N NAT 1 66.314 39.49761.6961.0038.29 B
B

ATCM 1743CA N~,'I'1 65.661 39.50060.3551.0039.16 B
B

ATCM 1744N LYS 2 65.312 41.03858.5121.0034.27 B
B

ATCM 1745CA LYS 2 65.080 42.33657.8871.0031.40 B
B

A~C,M CE LYS 2 66.279 42.72757.0161.0029.61 B

A'ICM OG LYS 2 66.155 44.10656.3711.0030.07 B

AICM 1748CD LYS 2 67.285 44.37955.3861.0029.11 B
B

ATCM 1749CE LYS 2 68.629 44.49956.0821.0029.13 B
B

A'IC~I NZ LYS 2 69.732 44.65655.0911.0029.05 B

AT~2 1751C LYS 2 63.813 42.26757.0391.0029.46 B
B

ATCM 1752O LYS 2 63.721 41.46656.1081.0028.29 B
B

A'IC~2 N ~E 3 62.833 43.10257.3611.002?.02 B

A2CM 1754CA aE 3 61.589 43.09456.6041.0027.ll B
B

AnM 1755 CB ~E 3 60.365 43.36957.5111.0026.84 B
B

AnM 1756 002~E 3 59.073 43.12956.7261.0025.34 B
B

A'I~ 1757C7 ~E 3 60.398 42.45158 1.0027 .20 i1.B .739 B

AnM 1758 CD1a.E 3 60.436 40.97758.4111.0028.05 8 B

AnM 1759 C ~E 3 61.597 44.12955.4821.0026.15 B
B

A~C~2 0 ~E 3 61.777 45,32555.7261.0026.07 B

AnM 1761 N C3~Y 4 61.417 43.65654.2511.0024.98 B
B

ABM 1762 C~1C3~Y 4 61. 44 53 1. 23 . 50 B 370 . ,109 00 B

A'ICM C C3~Y 4 59.945 45.05252.9421.0023.12 8 A'I~t O COY 4 58.992 44.28553.0851.0024.14 B

A'ICM N ~E 5 59.791 46.33652.6461.0023.73 B

A~2 1766 CA ~E 5 58.470 46.92752.4771.0023.35 B
B

A'IC~i C8 ~E 5 58.115 47.83653.6801.0024.38 B

A1TM 1768C02~E 5 56.699 48.38453.5321.0020.69 B
B

AnM 1769 0 B.E 5 58. 47 54. 1. 25. 50 i1 B 236 . 987 00 B

A'ICM CD1~E 5 58.062 47.92156.2271.0024.74 B

AnM 1771 C ~ B 5 58.436 47.77751.2131.0023.38 B

1772 O ~E 5 59.280 48.64751.0261.0024.52 B
B

A'!CM N aE 6 57.457 47.53050.3521,0022.48 B

A'ICM CA ~E 6 57.335 48.30049.1231.0022.19 B

ALCM 1775CB ~E 6 57.630 47.43247.8811.0022.96 B

ALCM 1776CJ02~E 6 57.412 48.24046.6161.0021.15 B
B

A'ICM C~1~E 6 59.072 46.93247.9291.0023.73 B

AIM 1778 CD1~E 6 59.384 45.86246.8991.0023.86 B
B

DEMANDES OU BREVETS VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVETS
COMPREND PLUS D'UN TOME.
CECI EST LE TOME ~ DE J
NOTE: Pour les tomes additionels, veillez contacter 1e Bureau Canadien des Brevets.
JUMBO APPLICATIONS l PATENTS
THIS SECTION OF THE APPLICATION / PATENT CONTAINS MORE
THAN ONE VOLUME.
THIS IS VOLUME I OF
NOTE: For additional volumes please contact the Canadian Patent Office.

Claims

1. A method of identifying a compound that affects MTA/AdoHcy nucleosidase activity, comprising obtaining a 3D structure of MTA/AdoHcy nucleosidase or fragment thereof, designing a compound to interact with the 3D structure of MTA/AdoHcy nucleosidase or fragment thereof, obtaining the compound, and determining whether the compound affects MTA/AdoHcy nucleosidase activity.

2. The method of claim 1, wherein the 3D structure of MTA/AdoHcy nucleosidase or fragment thereof comprises at least one of i) an active site ii) a 5' binding cavity and iii) a ribose binding site.

3. The method of claim 2, wherein designing a compound comprises comparing the structural coordinates of the compound to the structural coordinates of at least one of i) to iii) and determining whether the compound fits spatially into at least one of i) to iii) and is capable of a) changing MTA/AdoHcy nucleosidase from an open conformation to a closed conformation without nucleoside catalysis;
b) biasing MTA/AdoHcy nucleosidase toward a closed conformation; or c) preventing MTA/AdoHcy nucleosidase from changing toward a transition conformation or a closed conformation; wherein the ability of the compound to cause any of a) to c) indicates that the compound inhibits MTA/AdoHcy nucleosidase activity.

4. The method of claim 1, wherein the 3D structure is determined from one or more sets of structural coordinates in Tables 1 to 6.

5. The method of claim 1, further comprising introducing into a computer program the structural coordinates of claim 4 defining an MTA/AdoHcy nucleosidase, wherein the program generates the 3D structure of the MTA/AdoHcy nucleosidase.

6. The method of claim 4, wherein the MTA/AdoHcy nucleosidase comprises all or part of an amino acid sequence selected from the group consisting of (SEQ
ID NO:1), (SEQ ID NO:2), and (SEQ ID NO:3), all shown in Figure 19, and structurally equivalent and structurally homologous sequences having at least 60% sequence identity to (SEQ ID NO:1), (SEQ ID NO:2), and (SEQ ID NO:3).

7. The method of claim 1, wherein the MTA/AdoHcy nucleosidase is isolated from a bacterium selected from the group consisting of E. coli, S. aureus, and S.
pneumoniae.

8. The method of claim 7, wherein the 3D structure comprises a conformation selected from the group consisting of open, closed, and transition conformations.

9. The method of claim 8, wherein the conformation is open.

10. The method of claim 9, wherein:
a) the E.coli MTA/AdoHcy nucleosidase structure comprises the following amino acids:
i) adenine binding site: residues Phe151, Ile152, Ser196, Asp197, and Ala199;
ii) ribose binding site: residues Glu174, Ser76, Met9, Met173, Arg193, and Phe207;
iii) 5'-tail binding site: residues Met9, Ile50, (Val102, Phe105, Tyr107, Pro113), Phe151, Met173, and Phe207, wherein the residues in brackets are donated from a neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Table 1;
b) the S. aureus MTA/AdoHcy nucleosidase structure comprises the following amino acids:
i) adenine binding site: Ser75, Phe150, Ile151, Ser195, Asp196, and Ala198;
ii) ribose binding site: Met8, Ser75, Met172, Glu173;
iii) 5'-tail binding site: Met8, Ile49, Phe150, Met172, Phe206 and (Ala101, Phe104, Tyr106, and Pro112), wherein the residues in the brackets are from a neighbouring monomer; the amino acids arranged in an open conformation spatial relationship represented by the structural coordinates listed in Table 5;
and/or c) the S. pneumoniae MTA/AdoHcy nucleosidase structure comprises the following amino acids:
i) adenine binding site: Ser76, Phe151, Ile152, Ser196, Asp197, Ala199;
ii) ribose binding site: Met9, Ser76, Met173, Glu174; and/or iii) 5'-tail binding site: Met9, Ile50, Phe151, Met173, Phe207 and (Val102, Phe105, Tyr107, and Ala113), wherein the residues in the brackets are from a neighbouring monomer; the amino acids arranged in an open conformation spatial relationship represented by the structural coordinates listed in Table 6.

11. The method of claim 8, wherein the conformation is closed.

12. The method of claim 11, wherein the E. coli MTA/AdoHcy nucleosidase is complexed with FMA and the amino acids are arranged in a spatial relationship represented by the structural coordinates listed in Table 2.

13. The method of claim 11, wherein the MTA/AdoHcy nucleosidase is complexed with MTT and the amino acids are arranged in a spatial relationship represented by the structural coordinates listed in Table 3.

14. The method of claim 8, wherein the conformation is a transition conformation.

15. The method of claim 14, wherein the MTA/AdoHcy nucleosidase is complexed to AdoHcy.

16. The method of claim 14, wherein the MTA/AdoHcy nucleosidase structure comprises the following amino acids:
i) adenine binding site: residues Phe151,Ile152, Ser196, Asp197, and Ala199;
ii) ribose binding site: residues Glu174, Ser76, Met9, Met173, Arg193, and Phe207; and/or iii) 5'-tail binding site: residues Met9, Ile50, (Val102, Phe105, Tyr107, Pro113,) Phe151, Met173, and Phe207, wherein the residues in brackets are donated from a neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Table 4.

17. The method of claim 1, further comprising determining whether the compound interacts with the 3D structure of MTA phosphorylase or a fragment thereof and/or AdoHcy hydrolase or a fragment thereof and inhibits MTA

phosphorylase or AdoHcy hydrolase activity, wherein if the compound does not inhibit MTA phosphorylase or AdoHcy hydrolase activity, the compound is a selective inhibitor of MTA/AdoHcy nucleosidase.

18. The method of claim 17, wherein the fragment comprises at least one of i) an active site ii) a 5' binding cavity and iii) a ribose binding site.

19. The method of claim 17, wherein the MTA phosphorylase comprises the following amino acids:
i) adenine binding site: residues Phe177, Ser178, Thr219, Asp220 and Asp222;
ii) 5'-methylthioribose binding site: residues Met196, Val233, Val236, Leu237, (His237 and Leu279), wherein the residues in brackets are donated from a neighbouring subunit;
iii) sulfate/phosphate binding site: residues Thr18, Arg60, His61, Thr93, Ala94, and Thr197; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Protein Data Bank Accession No. 1CG6.

20. The method of claim 17, wherein the AdoHcy hydrolase comprises the following amino acids i) adenine binding site: residues Leu54, Thr57, Glu59, SeMet/Met351, His353, and SeMet/Met358;
ii) ribose binding site: residues His55, Glu156, Lys186, Thr157, and Asp190 and/or iii) homocysteinyl binding site: His55, Cys79, Asn80, Asp131, Asp134, and Leu344;
the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Protein Data Bank Accession No. 1A7A.

21. The method of claim 2, wherein:
i) the binding cavity of MTA/AdoHcy nucleosidase comprises amino acids Met9, Ile50, Val102, Phe105, Pro113, Met173, and Phe207 and (Val102, Phe105 and Pro113); wherein the residues in the brackets are from a neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in one of Tables 1 to 6;

ii) the binding cavity of MTA phosphorylase comprises amino acids Val236, Leu237, Val233, Leu279 and His137 and (Leu279 and His137) wherein the residues in the brackets are from a neighbouring monomer; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Protein Data Bank Accession No. 1CG6; and iii) the binding cavity of AdoHcy hydrolase comprises amino acids His55, Cys79, Asn80, Asp131, Asp134, and Leu344; the amino acids arranged in a spatial relationship represented by the structural coordinates listed in Protein Data Bank Accession No. 1A7A.

22. The method of claim 1, which further comprises: obtaining or synthesizing the compound, forming a MTA/AdoHcy nucleosidase:compound complex and analysing the complex by X-ray crystallography to determine the ability of the compound to interact with MTA/AdoHcy nucleosidase.

23. The method of claim 22, further comprising:
a) determining the three-dimensional structure of the supplemental crystal with molecular replacement analysis;
b) identifying or designing an inhibitor by performing rational drug design with the three-dimensional structure determined for the supplemental crystal or a fragment thereof.

24. The method of claim 1, further comprising determining whether the compound inhibits MTA phosphorylase or AdoHcy hydrolase.

25. The method of claim 1, wherein MTA/AdoHcy nucleosidase activity is determined by:
a) incubating a test sample comprising MTA/AdoHcy nucleosidase, (ii) the compound; and (iii) a substrate comprising 5'-methylthioadenosine or S-adenosylhomocysteine;
b) detecting substrate hydrolysis products in the test sample, wherein a change in the amount of substrate hydrolysis products in the test sample in the presence of the compound relative to in its absence indicates that the compound affects the MTA/AdoHcy nucleosidase activity.

26. The method of claim 25, further comprising:
a) contacting the compound with a MTA phosphorylase or AdoHcy hydrolase;
and b) measuring the activity of the MTA phosphorylase or AdoHcy hydrolase;
wherein a compound is identified for use as an inhibitor of MTA/AdoHcy nucleosidase when it inhibits MTA/AdoHcy nucleosidase and but does not change the activity of the MTA phosphorylase or AdoHcy hydrolase.

27. A compound obtained according to the method of claim 1.

28. A computer readable medium with either (a) structural coordinate data according to at least one of Tables 1 to 6 recorded thereon, the data defining the three-dimensional structure of the MTA/AdoHcy nucleosidase, MTA/AdoHcy nucleosidase bound to an inhibitor or a fragment of the foregoing, or (b) structural data for the MTA/AdoHcy nucleosidase, MTA/AdoHcy nucleosidase bound to an inhibitor or a fragment of the foregoing recorded thereon, the structural data being derivable from the structural coordinate data of at least one of Tables 1 to 6.

29. The computer medium of claim 28, wherein the structural coordinate data is obtained by x-ray diffraction with a crystal of the invention.

30. A computer system containing either (a) structural coordinate data according to at least one of Tables 1 to 6, the data defining the 3D structure of MTA/AdoHcy nucleosidase, MTA/AdoHcy nucleosidase bound to an inhibitor or a fragment of the foregoing, or (b) structural data for MTA/AdoHcy nucleosidase, MTA/AdoHcy nucleosidase bound to an inhibitor or a fragment of the foregoing, the structural data being derivable from the atomic coordinate data of at least one of Tables 1 to 6.

31. The computer system of claim 30, wherein the structural coordinate data is obtained by x-ray diffraction with a crystal of the invention.

32. A method of designing of an MTA/AdoHcy nucleosidase inhibitor through use of a crystal of the invention or structure coordinates derived therefrom.

33. The method of claim 32, wherein the microbe is selected from the group consisting of Streptococcus pyrogenes, Yersinia pestis, Vibrio cholerae, Haemophilus influenzae, Enterococcus faecalis, Helicobacter pylori, Mycobacterium tuberculosis, Staphylococcus aureus, Streptococcus pneumoniae, Campylobacter jejuni, Treponema pallidum, Borrelia burgdorferi, Salmonella typhimurium, Escherichia coli, Neisseria meningitides or Bacillus anthracis.

34. A method of treating a disease in a subject, comprising administering to the subject the compound of claim 27.

35. The method of claim 34, wherein the disease is caused by a microbe having MTA/AdoHcy nucleosidase.

36. The method of claim 35, wherein the microbe is selected from the group consisting of Streptococcus pyrogenes, Yersinia pestis, Vibrio cholerae, Haemophilus influenzae, Enterococcus faecalis, Helicobacter pylori, Mycobacterium tuberculosis, Staphylococcus aureus, Streptococcus pneumoniae, Campylobacter jejuni, Treponema pallidum, Borrelia burgdorferi, Salmonella typhimurium, Escherichia coli, Neisseria meningitides and Bacillus anthracis.

37. The method of claim 34, wherein the disease is selected from the group consisting of pharyngitis, scarlet fever, impetigo cellulites, bubonic plague, pneumonic plague, cholera pneumonia urinary tract infection peptic ulcer, gastritis, tuberculosis, staphyloenterotoxicosis, staphyloenterotoxemia, meningitis, pneumonia, infections campylobacteriosis, syphilis, Lyme disease, food poisoning, haemorrhagic colitis, meningitis and septicaemia.

38. A crystal comprising MTA/AdoHcy nucleosidase.