WO2005056593A2 - Interactions between hsp90 and p50/cdc37 - Google Patents

Abstract

The invention derives from the finding that the interaction between Hsp90 and p50cdc37 is mediated through the N-terminal domain of Hsp90, rather than the C-terminal domain as was previously thought. A crystal structure of a complex between the N-terminal domain of Hsp90 and the C-terminal domain of p50cdc37 is provided. The structure may be used for homology modelling and structure solution, as well as for identifying compounds which modulate the interaction between Hsp90 and p50cdc37.

Description

Interaction between Hsp90 and p50^cdc37

FIELD OF THE INVENTION

, The present invention relates to chaperone proteins, and in particular to the Hsp90 chaperone and its interaction with the p₅₀ ^cdc37 _co__cnaperone. Inter alia, methods are provided for the identification of inhibitors of Hsp90 activity, which may have therapeutic potential e.g. in the treatment of cancer. BACKGROUND TO THE INVENTION Hsp90 is a molecular chaperone with an essential role in eukaryotes in activation and maintenance of a wide range of regulatory and signalling proteins (Pearl and Prodromou, 2002; Picard, 2002; Pratt and Toft, 2003) . The largest coherent class of proteins amongst Hsp90s structurally and functionally varied clientele are the protein kinases . Known protein kinase clients in mammalian cells include : PKB/Akt (Sato et al . , 2000; Basso et al . , 2002; Fontana et al . , 2001), PDK1 (Fujita et al., 2002), LKB1 (Boudeau et al . , 2003), Raf-1 (Stancato et al., 1993; Schulte et al . , 1995; Grammatikakis et al . , 1999), ErbB2 (Xu et al . , 2001), Bσr-Abl (An et al . , 2000), Src-family kinases (Xu and Lindquist, 1993; Xu et al . , 1999; Bijlmakers and Marsh, 2000), Aurora B (Lange et al . , 2002), and the cyclin dependent kinases Cdk4, Cdkβ and Cdk9 (Stepanova et al., 1996; Mahony et al . , 1998; Okeeffe et al . , 2000). The involvement of Hsp90 in the activity of so many potentially oncogenic protein kinases has engendered considerable interest in Hsp90 as a target for cancer chemotherapy (reviewed in (Neckers, 2002; Maloney and Workman, 2002; Blagosklonny, 2002) ) .

Activation of Hsp90-dependent client proteins proceeds through an ordered sequence of complexes involving a variety of co- chaperones (reviewed in (Pearl and Prodromou, 2002)) . Hsp90- dependent protein kinases in mammalian cells are particularly associated with a 50 kDa protein (Brugge, 1986) , whose N- terminal region has strong homology to the equivalent region of Cdc37p from budding yeast (Perdew et al . , 1997; Stepanova et al., 1996). Functional dissection of this protein, p50^cdc37, identified a protein kinase-binding domain at the N-terminus (Grammatikakis et al . , 1999), while the C-terminal region was found to interact with Hsp90 (Shao et al . , 2001). Thus, p50^cdc37 acts as an adaptor or scaffold, facilitating protein kinase interaction with the Hsp90 molecular chaperone (Silverstein et al., 1998). Binding to p50^cdc37 is highly specific, and otherwise closely related protein kinases may differ substantially in their interaction. Thus Cdk4 associates with p50^cdc37, whereas Cdk2 does not (Dai et al . , 1996; Stepanova et al., 1996). Similarly, the MAP-kinase MOK binds p50cdc37, while ERK, NK and p38 do not (Miyata et al . , 2001) .

While the majority of Hsp90-dependent protein kinases so far identified are also dependent on p50^cdc37 (Hunter and Poon, 1997) , the converse may not always be true and for some kinases interaction with p50^cdc37 alone may be sufficient to afford a degree of stabilisation (Tatebe and Shiozaki, 2003; Lee et al . , 2002) .

We have previously shown that p50^cdc37 is not a passive scaffold, but is an active Hsp90 co-chaperone participating in regulation of the Hsp90 chaperone cycle (Siligardi et al . , 2002) . Thus, like the TPR-domain co-chaperone Hop/Stil

(Prodromou et al . , 1999; Richter et al . , 2003), p50^cdc37 is able to arrest the ATPase cycle to facilitate client protein loading. This property resides in the C-terminal part of the molecule and is retained, although to a lesser degree, in the yeast Cdc37p, whose C-terminus has only low homology to its mammalian homologues . In order to define the nature of the functional interaction between p50^cdc37 and Hsp90, we have mapped the p50^cdc37-binding region in Hsp90 to the N-terminal nucleotide-binding domain and determined the crystal structure of the core Hsp90-p50^cdc37 complex. The structure reveals the mechanism by which p50^cdc37 arrests the ATPase cycle of Hsp90, locking the 'lid' of the nucleotide binding pocket in an open conformation, and holding the 'jaws' of the Hsp90 molecular clamp apart to facilitate client protein loading.

Definitions In the following by "binding site" we mean a site (such as an atom, a functional group of an amino acid residue or a plurality of such atoms and/or groups) in a binding cavity which may bind to an agent compound such as a modulator (e.g. inhibitor) of Hsp90 activity. Depending on the particular molecule in the cavity, sites may exhibit attractive or repulsive binding interactions, brought about by charge, steric considerations and the like.

By Hsp90 is meant a protein which has a sequence identity of equal to or greater than 40% at the amino acid level with residues 1 to 208 of the N-terminal domain of yeast Hsp90 protein (Bussey et al . , 1997, Nature 387 (6632 Suppl) : 103- 105), and preferably having greater than 50%, 60%, 70%, 80% or 90% identity with that sequence. Hsp90 activity means the ability of an Hsp90 protein to activate a client protein, e.g. a kinase, or alternatively refers to the ATPase activity of Hsp90 which is required for its chaperone function.

By p50^cdc37 is meant a protein which has a sequence identity of equal to or greater than 40% at the amino acid level with residues 140 to 378 of the C-terminal domain of human p50^cdc37 as shown in Figure 2, and preferably having greater than 50%, 60%, 70%, 80% or 90% identity with that sequence, or proteins known to be functionally identical to human p50^cdc3?. Thus this includes the corresponding proteins from X. laevis, T. fluviatilis, D. melanogaster, C. elegans as well as the Cdc37 protein from 5. cerevisiae .

By "fitting", is meant determining by manual, automatic, or semi-automatic means, interactions between one or more atoms of a candidate or agent molecule and one or more atoms or binding sites of the molecule to which the candidate molecule is to be fitted (in the context of the present invention typically Hsp90 and/or p50^cdc37) , and calculating the extent to which such interactions are stable. Various computer-based methods for fitting are described further herein.

By "root mean square deviation" we mean the square root of the arithmetic mean of the squares of the deviations from the mean.

By a "computer system" we mean the hardware means, software means and data storage means used to analyse atomic coordinate data. The minimum hardware means of the computer-based systems of the present invention comprises a central processing unit (CPU) , input means, output means and data storage means. Desirably a monitor is provided to visualise structure data. The data storage means may be RAM or means for accessing computer readable media of the invention. Examples of such systems are microcomputer workstations available from Silicon Graphics Incorporated and Sun Microsystems running Unix based, Windows NT or IBM OS/2 operating systems .

By "computer readable media" we mean any media which can be read and accessed directly by a computer e.g. so that the media is suitable for use in the above-mentioned computer system. Such media 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 magnetic/optical storage media .

DISCLOSURE OF THE INVENTION

The present invention derives from the realisation that, contrary to what was previously thought, the interaction between Hsp90 and p50^cdc37 is mediated through the N-terminal domain of Hsp90. Following on from this finding, the N- terminal domain of yeast Hsp90 has been crystallised with the C-terminal domain of human p50^cdc3?, which has enabled the mechanism by which p50^cdc37 inhibits the ATPase activity of Hsp90 to be elucidated.

In general terms the present invention is concerned with identifying or obtaining agent compounds for modulating Hsp90 activity, and in preferred embodiments identifying agent compounds which inhibit Hsp90 activity. Where methods of identifying or modelling inhibitors are described hereinafter, the skilled person will appreciate that the processes may be applied analogously to other modulators such as activators.

Crystal structure information presented herein is useful in designing potential modulators and modelling them or their potential interaction with Hsp90 binding cavities, possibly formed in conjunction with p50^cdc37, for example, the ATP binding pocket or other regions of interest such as binding sites for Hsp90-dependent client proteins and/or other co- chaperones of Hsp90. Potential modulators may be brought into contact with the Hsp90 molecule or the Hsp90-p50^cdc37 complex to test for ability to interact with an Hsp90 binding cavity. Actual modulators may be identified from among potential modulators synthesized following design and model work performed in silico. A modulator identified using the present invention may be formulated into a composition, for instance a composition comprising a pharmaceutically acceptable excipient, and may be used in the manufacture of a medicament for use in a method of treatment. These and other aspects and embodiments of the present invention are discussed below.

In a first aspect the present invention provides a crystal of a complex between Hsp90 and p50^cdc37 having a space group P3_X21 or its enantiomorph and unit cell dimensions of a = 83.76 A, c = 148.45 A, and more generally a = 83.76±0.2 A,, c = 148.45+0.2 A, or a = 83.76+0.5 A, C = 148.45±0.5 A. Additionally or alternatively the crystal may have the three- dimensional atomic coordinates of Table 2.

The coordinates of Table 2 provide a measure of atomic location in Angstroms. The coordinates are a relative set of positions that define a shape in three dimensions, so the skilled person would understand that an entirely different set of coordinates having a different origin and/or axes could define a similar or identical shape. Furthermore, the skilled person would understand that varying the relative atomic positions of the atoms of the structure so that the root mean square deviation of the residue backbone atoms (i.e. the nitrogen-carbon-carbon backbone atoms of the protein amino acid residues) is less than 1.5 A (preferably less than 1.0 A and more preferably less than 0.5 A) when superimposed on the coordinates provided for the residue backbone atoms, will generally result in a structure which is substantially the same as the structure of Table 2 in terms of both its structural characteristics and usefulness for structure-based analysis, including design of Hsp90 modulators.

Likewise the skilled person would understand that changing the number and/or positions of the water molecules in these structures (where shown) will not generally affect the usefulness of the structure for structure-based analysis.

Thus for the purposes described herein as being aspects of the present invention, it is within the scope of the invention if: the coordinates are transposed to a different origin and/or axes; the relative atomic positions of the atoms of the structure are varied so that the root mean square deviation of residue backbone atoms is less than 1.5 A (preferably less than 1.0 A and more preferably less than 0.5 A) when superimposed on the coordinates provided in Table 2 for the residue backbone atoms . Reference herein to the coordinate data of Table 2 thus includes the coordinate data in which one or more individual values of the Table are varied in this way. Modifications in the native structures of Hsp90 or p50^cdc37 due to e.g. mutations, additions, substitutions, and/or deletions of amino acid residues could lead to variations in the atomic coordinates shown and where such modified forms of these proteins are being investigated, atomic coordinate data of Table 2 modified so that a ligand that bound to one or more binding sites of Hsp90 or p50^cdc37 would be expected to bind to the corresponding binding sites of the modified Hsp90 or p50^cdc37 are, for the purposes described herein as being aspects of the present invention, also within the scope of the invention. Reference herein to the coordinates of Table 2 thus includes the coordinates modified in this way. Preferably, the modified coordinate data define at least one binding site.

The crystal may comprise a substrate molecule or analogue thereof bound to Hsp90. For example the crystal may comprise an ATP molecule, a drug capable of binding to the ATP binding site, such as geldanamycin, or a non-hydrolysable analogue of ATP, such as ATP-gammaS.

In preferred embodiments, the Hsp90 molecule within the crystal lacks some or all of C-terminal domain, and may also lack some or all of the M, or middle, domain . The C-terminal and M domains of yeast Hsp90 consist of amino acid residues 600 to 709 and 255 to 599 respectively of the sequence provided in Bussey et al . , 1997. Corresponding regions of other Hsp90 sequences may also be used.

The Hsp90 molecule may consist of or comprise the entire N- terminal domain. Thus it may consist of or comprise residues corresponding to residues 1 to 220 of yeast Hspl or a portion thereof, e.g. corresponding to residues 1 to 208 of yeast Hsp90. The N-terminal domain in the native protein displays ATPase activity, but references to this domain should not be interpreted to require the domain present in the crystal to be capable of hydrolysing ATP. For example, the Hsp90 may contain a mutation which impairs or abrogates the ATPase activity, e.g. at the ATP binding site, but does not affect the gross structure of the domain.

The p50^cdc37 molecule in the crystal may lack some or all of the N-terminal domain, which is defined as residues 1 to 140 in the human p50^cdc37 sequence shown herein. Preferably the p50^cdc37 molecule consists of or comprises the entire C-terminal domain, and in a preferred embodiment consists of residues corresponding to 138 to 378 of the human sequence.

In preferred embodiments the Hsp90 molecule is human or yeast (e.g. S. cerevisisae) . The p50^cdc37 molecule is preferably human .

In another aspect, the present invention provides a method of determining the structure of a complex between Hsp90 and p₅₀ ^cdc37 _comp_ri_si_ng the step of X-ray diffraction analysis of a crystal as described herein.

The crystals described herein, and the three-dimensional coordinate data which they provide, may be used to assist in the solution of a structure for a complex of Hsp90 and p50^cdc37 having a ligand bound to either or both of the Hsp90 and p50^cdc37. Thus in a further aspect, the present invention provides a method of analysing binding between a complex of Hsp90 and p50^cdc37 and a ligand, the ligand being bound to either or both of Hsp90 and p50^cdc37, the method comprising the step of employing (i) X-ray crystallographic diffraction data from the complex between Hsp90, p50^cdc37 and said ligand, and

(ii) a three-dimensional structure of a complex between Hsp90 and p50^cdc37 defined by atomic coordinate data according to Table 2, to generate a difference Fourier electron density map of the complex between Hsp90, p50^cdc37 and said ligand. If the complex is crystallised in a different space group to the crystals described herein, molecular replacement methods may be used instead of difference Fourier methods . Therefore, in the light of the present disclosure, Hsp90/p50^cdc37/ligand complexes can be crystallised and analysed using X-ray diffraction methods, e.g. according to the approach described by Greer et al . , J. of Medicinal Chemistry, Vol. 37, (1994), 1035-1054, and difference Fourier electron density maps can be calculated based on X-ray diffraction patterns of soaked or co-crystallised Hsp90/p50^cdc37 and ligand and the solved structure of the simple Hsp90/p50^cdc37 complex. These maps can then be used to determine whether and where a particular ligand binds to the complex and/or changes its conformation.

Electron density maps can be calculated using programs such as those from the CCP4 computing package (Collaborative

Computational Project 4. The CCP4 Suite: Programs for Protein Crystallography, Acta Crystallographica, D50, (1994), 760- 763. ) . For map visualisation and model building programs such as O (Jones et al . , Acta Crystallography, A47, (1991), 110- 119) can be used.

In a further aspect, the present invention relates to methods for using the three-dimensional structural data provided herein in determining structures for complexes between Hsp90 and p50^cdc37 molecules other than those used in the examples. These methods may be used for determining structures for complexes comprising Hsp90 and/or p50^odc37 molecules from other species, complexes containing alternative isoforms of Hsp90 and p50^cdc37 , and complexes comprising mutants or derivatives of the Hsp90 and p50^cdc37 molecules described herein.

The primary ways in which the three-dimensional coordinate data of the present invention can be used to solve other target structures are as follows:

The three-dimensional coordinate data provided herein for yeast Hsp90 and/or human p50^cdc37 may be aligned with an amino acid sequence of a target Hsp90 and/or p50^cdc37 to match homologous regions of the amino acid sequences, and a structure determined for the target by homology modelling.

The three-dimensional coordinate data of the present invention may be used to assist in interpretation of a set of raw X-ray crystallographic data obtained for a complex comprising a target Hsp90 and/or p50^cdc37, in order to establish a structure for the target molecules (s) .

Typically, in each of these alternatives, the target structure will be established by the calculation of a set of three- dimensional coordinate data for some or all of the atoms in the target structure .

Homology Modelling

Thus the invention provides a method of determining a three dimensional structure for a complex between Hsp90 and p50^cdc37 by homology modelling, comprising the steps of: (a) aligning a representation of an amino acid sequence of a target Hsp90 and/or p50^cdc37 with the amino acid sequence of yeast Hsp70 and/or human p50^cdc37 to match homologous regions of the amino acid sequences;

(b) modelling the structure of the matched homologous regions of the target Hsp90 and/or p50^cdc37 on the structure of the corresponding regions of yeast Hsp90 and/or human p50^cdc37 as defined by Table 2; and

(c) determining a conformation for the target Hsp90 and/or p50-^dc-⁷ _w]₁i_cι₁ substantially preserves the structure of said matched homologous regions.

The term "homologous regions" describes amino acid residues in two sequences that are identical or have similar (e.g. aliphatic, aromatic, polar, negatively charged, or positively charged) side-chain chemical groups. Identical and similar residues in homologous regions are sometimes described as being respectively "invariant" and "conserved" by those skilled in the art .

Preferably one or all of steps (a) to (c) are performed by computer modelling.

Homology modelling is a technique that is well known to those skilled in the art (see e.g. Greer, Science, Vol. 228, (1985), 1055, and Blundell et al . , Eur. J. Biochem, Vol. 172, (1988), 513) . By "homology modelling", is meant the prediction of related structures based either on x-ray crystallographic data or computer-assisted e novo prediction of structure, based upon manipulation of the coordinate data of Table 2.

The various in silico modelling techniques described in this section and in the other sections of this application may utilize coordinates from the crystal data set provided herein, or from any structure calculated by means of that data set .

"Homology modelling" extends to target molecules which are analogues or homologues of the Hsp90 and p50^cdc37 molecules whose structure in complex together has been determined in the accompanying examples . It also extends to mutants of these proteins .

In general, comparison of amino acid sequences is accomplished by aligning the amino acid sequence of a polypeptide of a known structure with the amino acid sequence of the polypeptide of unknown structure. Amino acids in the sequences are then compared and groups of amino acids that are homologous are grouped together. This method detects conserved regions of the polypeptides and accounts for amino acid insertions or deletions.

Homology between amino acid sequences can be determined using commercially available algorithms. The programs BLAST, gapped BLAST, BLASTN, PSI-BLAST and BLAST 2 sequences (provided by the National Center for Biotechnology Information) are widely used in the art for this purpose, and can align homologous regions of two amino acid sequences . These may be used with default parameters to determine the degree of homology between the amino acid sequence of the protein of known structure and other target proteins which are to be modeled.

Analogues are defined as proteins with similar three- dimensional structures and/or functions and little evidence of a common ancestor at a sequence level. For example, in view of their low degree of sequence identity with one another, S. cerevisiae Cdc37 may be regarded as an analogue of human p50^cdc37.

Homologues are defined as proteins with evidence of a common ancestor i.e. likely to be the result of evolutionary divergence and are divided into remote, medium and close subdivisions based on the degree (usually expressed as a percentage) of sequence identity.

A homologue is defined here as a protein with at least 40% sequence identity with the N-terminal domain of yeast Hsp90 or the C-terminal domain of human p50^cdc37 as described above, including polymorphic forms of those molecules.

A mutant is a molecule characterized by replacement or deletion of at least one amino acid from a wild type Hsp90 or p50^cdc37. Such a mutant may be prepared for example by site- specific mutagenesis, or incorporation of natural or unnatural amino acids.

The present invention contemplates "mutants", and the application of the methods of the present invention to "mutants" , wherein a "mutant" refers to a polypeptide which is obtained by replacing at least one amino acid residue in a native or synthetic molecule with a different amino acid residue and/or by adding and/or deleting amino acid residues within the native polypeptide or at the N- and/or C-terminus of a polypeptide corresponding to a wild-type molecule and which has substantially the same three-dimensional structure as the molecule from which it is derived. By having substantially the same three-dimensional structure is meant having a set of atomic structure co-ordinates that have a root mean square deviation (r.m.s.d.) of less than or equal to about 2. oA when superimposed with the atomic structure coordinates of the wild-type molecule from which the mutant is derived when at least about 50% to 100% of the C_α atoms of the molecule are included in the superposition. A mutant may have, but need not have, enzymatic or catalytic activity corresponding to the activity of the wild type molecule from which it is derived.

To produce homologues or mutants, amino acids present in the said protein can be replaced by other amino acids having similar properties, for example hydrop obicity, hydrophobic moment, antigenicity, propensity to form or break ..-helical or /J-sheet structures, and so. Substitutional variants of a protein are those in which at least one amino acid in the protein sequence has been removed and a different residue inserted in its place. Amino acid substitutions are typically of single residues but may be clustered depending on functional constraints e.g. at a crystal contact. Preferably amino acid substitutions will comprise conservative amino acid substitutions. Insertional amino acid variants are those in which one or more amino acids are introduced. This can be amino-terminal and/or carboxy-terminal fusion as well as intrasequence . Examples of amino-terminal and/or carboxy- terminal fusions are affinity tags, an MBP tag, and epitope tags.

Amino acid substitutions, deletions and additions which do not significantly interfere with the three-dimensional structure of the molecule will depend, in part, on the region of the molecule where the substitution, addition or deletion occurs. In highly variable regions of the molecule, non-conservative substitutions as well as conservative substitutions may be tolerated without significantly disrupting the three- dimensional structure of the molecule. In highly conserved regions, or regions containing significant secondary structure, conservative amino acid substitutions are preferred.

Conservative amino acid substitutions are well-known in the art, and include substitutions made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity and/or the amphipathic nature of the amino acid residues involved. For example, negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; amino acids with uncharged polar head groups having similar hydrophilicity values include the following: leucine, isoleucine, valine; glycine, alanine; asparagine, glutamine; serine, threonine; phenylalanine, tyrosine . Other conservative amino acid substitutions are well known in the art.

In some instances, it may be particularly advantageous or convenient to substitute, delete and/or add amino acid residues to a particular binding site or catalytic residue, in order to provide convenient cloning sites in cDNA encoding the polypeptide, to aid in purification of the polypeptide, etc. Such substitutions, deletions and/or additions which do not substantially alter the three dimensional structure of the wild-type molecule will be apparent to those having skills in the art .

It should be noted that the mutants contemplated herein need not exhibit enzymatic activity. Indeed, amino acid substitutions, additions or deletions that interfere with catalytic activity (e.g. ATPase activity) but which do not significantly alter the three-dimensional structure of the catalytic region are specifically contemplated by the invention. Such crystalline polypeptides, or the atomic structure co-ordinates obtained therefrom, can be used to identify compounds that bind to the protein.

Once the amino acid sequences of the polypeptides with known and unknown structures are aligned, the structures of the conserved amino acids in a computer representation of the polypeptide with known structure are transferred to the corresponding amino acids of the polypeptide whose structure is unknown. For example, a tyrosine in the amino acid sequence of known structure may be replaced by a phenylalanine, the corresponding homologous amino acid in the amino acid sequence of unknown structure.

The structures of amino acids located in non-conserved regions may be assigned manually by using standard peptide geometries or by molecular simulation techniques, such as molecular dynamics. The final step in the process is accomplished by refining the entire structure using molecular dynamics and/or energy minimization.

Structure Solution

In a further aspect, the invention provides a method of determining a three dimensional structure for a complex between Hsp90 and p50^cdc37, comprising the steps of; providing the co-ordinates of Table 2, and positioning the coordinates in the crystal unit cell of a target Hsp90 and/or p50^cdc37 so as to provide a structure for said target Hsp90 and/or p50^cdc37.

The structure provided of the complex between Hsp90 and p50^cdc37 can be used to solve the crystal structure of other target Hsp90 and p50^dc37 molecules including other crystal forms, mutants, and co-complexes, where X-ray diffraction data of these target proteins has been generated and requires interpretation in order to provide the structure. Thus the present invention allows the structures of such targets to be obtained more readily where raw X-ray diffraction data is generated.

Where X-ray crystallographic or NMR spectroscopic data is provided for a complex comprising such target molecules having an unknown three- dimensional structure, the structure defined by Table 2 may be used to interpret that data to provide a likely structure for the target molecules by techniques which are well known in the art, e.g. phasing in the case of X-ray crystallography and assisting peak assignments in NMR spectra.

One method that may be employed for these purposes is molecular replacement. In this method, the unknown crystal structure, may be determined using the data set as provided herein. This method will provide an accurate structural form for the unknown crystal more quickly and efficiently than attempting to determine such information ah ini tio.

Examples of computer programs known in the art for performing molecular replacement are CNX (Brunger A.T.; Adams P.D.; Rice L.M., Current Opinion in Structural Biology, Volume 8, Issue 5, October 1998, Pages 606-611 (also commercially available from Accelerys San Diego, CA) or AMORE (Navaza, J. (1994) . AMoRe: an automated package for molecular replacement. Acta Cryst. A50, 157-163) .

The invention may also be used to assign peaks of NMR spectra of such proteins, by manipulation of the data provided herein.

Computer Systems

In another aspect, the present invention provides systems, particularly a computer system, intended to generate structures and/or perform rational drug design for Hsp90, Hsp90 complexes or Hsp90 homologues or mutants, the system containing either (a) atomic coordinate data according to Table 2 recorded thereon, or at least selected coordinates thereof; (b) structure factor data for the Hsp90-p50^cdc37 complex recorded thereon, the structure factor data being derivable from the atomic coordinate data of Table 2; (c) a Fourier transform of atomic coordinate data according to Table 2, or at least selected coordinates thereof; (d) atomic coordinate data of a target Hsp90 and/or p50^cdc37 generated by homology modelling of the target based on the data of Table 2; (e) atomic coordinate data of a target generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Table 2; or (f) structure factor data derivable from the atomic coordinate data of (d) or (e) .

The invention also provides such systems containing atomic coordinate data of target Hsp90 and/or p50^cdc37 molecules or complexes wherein such data has been generated according to the methods of the invention described herein based on the starting data provided by Table 2.

Such data is useful for a number of purposes, including the generation of structures to analyze the mechanisms of action of Hsp90, and/or to perform rational drug design of compounds which interact with them, such as modulators of Hsp90 activity, e.g. activators or inhibitors.

In a further aspect, the present invention provides computer readable media with either (a) atomic coordinate data according to Table 2 recorded thereon, or at least selected coordinates thereof; (b) structure factor data for the Hsp90- p50^cd-³⁷ complex recorded thereon, the structure factor data being derivable from the atomic coordinate data of Table 2;

(c) a Fourier transform of atomic coordinate data according to Table 2, or at least selected coordinates thereof; (d) atomic coordinate data of a target Hsp90 and/or p50^cdc37 generated by homology modelling of the target based on the data of Table 2 ; (e) atomic coordinate data of a target generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Table 2; or (f) structure factor data derivable from the atomic coordinate data of (d) or (e) .

By providing such computer readable media, the atomic coordinate data can be routinely accessed to model the Hsp90- p50^c-^c-⁷ complex or selected coordinates thereof. For example, RASMOL (Sayle et al . , TIBS, Vol. 20, (1995), 374) is a publicly available computer software package which allows access and analysis of atomic coordinate data for structure determination and/or rational drug design.

On the other hand, structure factor data, which are derivable from atomic coordinate data (see e.g. Blundell et al . , in Protein Crystallography, Academic Press, New York, London and San Francisco, (1976) ) , are particularly useful for calculating e.g. difference Fourier electron density maps.

In further aspects the present invention provides methods for modelling the interaction between a complex of Hsp90 and p50^cdc37 and one or more candidate compounds. Such modelling may, for example, be undertaken with a view to identifying modulators of Hsp90 activity, or elucidating the mechanism of action of an Hsp90 modulator.

Thus the invention provides a method for modelling an interaction between a complex of Hsp90 and p50^cdc37 and a candidate compound, comprising the steps of: (a) employing three-dimensional atomic coordinate data of Table 2 to characterise at least one binding site; (b) providing the structure of said candidate compound (c) fitting said candidate compound to the binding site.

Also provided is a method for identifying an agent compound which modulates Hsp90 activity, comprising the steps of: (a) employing a three-dimensional structure of a complex between Hsp90 and p50^cdc37, defined by atomic coordinate data according to Table 2, to characterise at least one binding site; (b) providing the structure of a candidate agent compound; (c) fitting the candidate agent compound to the binding site; and (d) selecting the candidate agent compound.

Agent compounds identified by such methods will desirably be modulators, and preferably inhibitors, of Hsp90 activity. That is to say they will typically inhibit the activation of a client protein by Hsp90. This may be achieved by inhibiting the ATPase activity of Hsp90 which is required for the protein to exert its chaperone activity.

The present invention allows the skilled person to select or design modulators having any of a number of different modes of action or selectivity for the type of client protein whose activation is to be inhibited.

Known Hsp90 clients include a large number of kinases, the steroid hormone receptors (e.g. the oestrogen, progesterone and glucocorticoid receptors) , endothelial nitric oxide synthase (eNOS) and telomerase. These clients can be crudely divided into those whose activation is also p50^cdc37-dependent and those which are not. Hsp90 clients which are also p50^cdc37- dependent include most of the Hsp90 -dependent kinases (including PKB/Akt, PDK1, LKB1, Raf-1, ErbB2, Bcr-Abl, Srσ- family kinases, Aurora B, heme-regulated eIF2alpha kinase, stress-activated protein kinase, Polo, MOK, and the cyclin dependent kinases Cdk4 , Cdk6 and Cdk9, but not Cdk2) .

Thus a Hsp90 inhibitor which binds preferentially to the Hsp90-p50^cdc37 complex rather than to Hsp90 alone or in other complexes will selectively inhibit activation of p50^{cd 37}- dependent clients. Conversely those inhibitors which bind preferentially to Hsp90 when it is not present in a complex with p50^cdc37 will tend to inhibit activation of non—p50^cdc37- dependent clients. Inhibitors of this class that bind in competition with p50^cdc37 will have the further desirable characteristic of preventing recruitment of p50^cdc37-dependent clients to Hsp90 thereby preventing their activation. Inhibitors which bind more or less equally well to Hsp90 whether or not it is complexed with p50^cdc37 will act to inhibit activation of all varieties of Hsp90 clients. The present invention provides means to identify and/or distinguish inhibitors falling into each of these categories.

It may be desirable to compare the structures of the free form of Hsp90 (i.e. that not complexed with p50^cdc37 - see for example Prodromou et al . , 1997a, b) and the complexed form of the protein, in order to identify binding sites present on only one of said conformations. The three-dimensional coordinate data for such a site could then be used to identify a ligand capable of binding selectively to, and stabilising, that conformation.

Thus the method may comprise the step of comparing the three- dimensional structure of Hsp90 when complexed with p50^cdc37, or the structure of the complex itself, with a three dimensional structure of Hsp90 which is not in such a complex, to identify a binding site which is: (i) exposed on Hsp90 when not complexed with p50^cdc37 but not exposed in said complex; or (ii) exposed only in said complex; or (iii) exposed on Hsp90 whether in said complex or not.

In case (i) , the binding site may be masked sterically or by a conformational change on binding of p50^cαc37 to Hsp90. For example, the candidate agent compound which binds to the ATP binding pocket may be blocked from binding by insertion of Arg 167 of p50^cdc37 into the ATP binding pocket

In case (ii) the binding site may comprise residues from both p₅Q_^dc37 _an^ jjsp90, or may be exposed by a conformational change on binding of p50^cdc37 to Hsp90. For example the binding site may comprise one or more residues corresponding to the yeast Hsp90 lid section between Gly 100 and Gly 121, which moves on binding of p50^cdc37, or may comprise one or more residues corresponding to the section from Leu 93 to Gly 100, e.g. lie 96 , Ala 97 and/or Lys 98.

In this case, the binding site may be chosen so that it does not comprise Hsp90 surface residues which interact with p50^cdc37. These residues may include residues corresponding to Ala 103, Ala 107, Ser 109, Ala 110, Gly 111, Ala 112, Met 116, Gin 119 and Phe 120 of yeast Hsp90. All the residues in contact with p50^cdc37 are identical to those in both of the human cytoplasmic Hsp90 isoforms, with the exception of Ser 109 on the edge of the lid, which participates in a hydrogen bond to the side-chain of p50^cdc37 Lys 202 - an interaction also available to the glutamine found at this position in human Hsp90.

In any of the cases (i) to (iii) , the binding site may comprise one or more residues lying within the ATP binding site of Hsp90.

For example, the binding site may comprise one or more amino acid residues corresponding to Glu 33 or Asp 79 of yeast Hsp90.

Where the binding site also comprises residues from p50^cdc37, these may be amino acid residues corresponding to Arg 167 of human p50^cdc37.

When the candidate agent compound is fitted to the binding site, an interaction between said candidate agent compound and the binding site may mimic an interaction formed between one or more of the following sets of residues on binding of human _p50cdc37 _{and yeast} Hsp90: Ala 103 of Hsp90 and Met 164 of p50^cdc37; Glu 106 of Hsp90 and Ala 204 of p50^cdc37; Ala 107 of Hsp90 and Met 164 of p50^cdc37; Ser 109 of Hsp90 and Lys 202 of p50^cdc37; Ala 110 of Hsp90 and Ala 204 of p50^cdc37; Ala 112 of Hsp90 and Met 164 of p50^cdα37 _; Met 116 of Hsp90 and Met 164 of p50^cdc37; Gin 119 of Hsp90 and Leu 165 of p50^cdc37; Gin 119 of Hsp90 and Glu 221 of p50^cdc37 _; Phe 120 of Hsp90 and Met 164 of p50^cdc37; Glu 33 of Hsp90 and Arg 167 of _p50c^dc37. _{Ser 36 of Hsp90 and Arg 167} of p50^cdc37.

Preferred interactions to be mimicked include those between Glu 106 of Hsp90 and Ala 204 of p50^cdc37; Ser 109 of Hsp90 and Lys 202 of p50^cdc37; ; Gin 119 of Hsp90 and Leu 165 of p50^cdc37; Gin 119 of Hsp90 and Glu 221 of p50^cdc37 _; Glu 33 of Hsp90 and Arg 167 of p50^cdc37 _; Ser 36 of Hsp90 and Arg 167 of p50^cdc37.

An interaction between a candidate agent compound and Hsp90 is considered to mimic an interaction between p50^cdc37 and that residue if atoms from the candidate agent compound make similar interactions with corresponding residues in the binding site, e.g. ionic bonds, and electrostatic interactions such as salt bridges, hydrogen bonds, and van der Waals interactions, as well as hydrophobic interactions.

Preferably the atoms from the candidate agent compound, when fitted to the binding site, lie at a similar distance from atoms of the relevant residue as atoms of p50^cdc37 when fitted to the binding site. An interaction between the candidate agent compound and the binding site may be considered to mimic an interaction between p50^cdc37 and the binding site if the relevant atoms have the relevant separations as derivable from the crystallographic data of Table 2 +/- lA, preferably +/- 0.5A, more preferably +/- 0.2A.

Preferably a plurality of binding sites, e.g. two, three or four binding sites, are characterised. A plurality of agent compounds may be fitted to said sites and the respective compounds linked to form a potential modulator compound. An understanding of the residues involved in the interaction of Hsp90 with ATP and with the p50^cdc37 molecule allows the development of specific and potent inhibitors of Hsp90 ATPase. This information may thus be used to develop potent and specific small molecule inhibitors in a number of ways. The Hsp90-p50^cdc37 complex may be co-crystallised with potential inhibitors or lead compounds identified through the methods described herein, or those discovered in high-throughput screening programmes known to the skilled person, and/or existing crystals may be soaked with such compounds. Alternatively, or additionally, rational drug design programmes may make full use of the crystallographic coordinates. These techniques are discussed in more detail below.

Thus the candidate agent compound maybe selected by computationally screening a database of compounds for interaction with said binding site.

More specifically, a potential modulator of Hsp90 activity can be examined through the use of computer modelling using a docking program such as GRAM, DOCK, or AUTODOCK (see Walters et al., Drug Discovery Today, Vol .3 , No.4, (1998), 160-178, and Dunbrack et al . , Folding and Design, 2, (1997), 27-42). This procedure can include computer fitting of candidate inhibitors to Hsp90 and optionally to p50^cdc37 to ascertain how well the shape and the chemical structure of the candidate inhibitor will bind to the enzyme.

Also computer-assisted, manual examination of the binding cavity structure of Hsp90/ p50^cdc37 may be performed. The use of programs such as GRID (Goodford, J. Med. Chem. , 28, (1985), 849-857) - a program that determines probable interaction sites between molecules with various functional groups and the enzyme surface - may also be used to analyse the binding cavity to predict partial structures of inhibiting compounds. Computer programs can be employed to estimate the attraction, repulsion, and steric hindrance of the two binding partners (e.g. Hsp90 and a candidate inhibitor) . Generally the tighter the fit, the fewer the steric hindrances, and the greater the attractive forces, the more potent the potential modulator since these properties are consistent with a tighter binding constant. Furthermore, the more specificity in the design of a potential drug, the more likely it is that the drug will not interact with other proteins as well. This will tend to minimise potential side-effects due to unwanted interactions with other proteins .

In one embodiment a plurality of candidate agent compounds are screened or interrogated for interaction with the binding sites. In one example, step (b) involves providing the structures of the candidate agent compounds, each of which is then fitted in step (c) to computationally screen a database of compounds (such as the Cambridge Structural Database) for interaction with the binding sites. In another example, a 3-D descriptor for the agent compound is derived, the descriptor including e.g. geometric and functional constraints derived from the architecture and chemical nature of the binding cavity. The descriptor may then be used to interrogate the compound database, the identified agent compound being the compound which matches with the features of the descriptor. In effect, the descriptor is a type of virtual pharmacophore .

A descriptor may further incorporate features derived from that part of p50^σdc37 which interacts with ATP binding site, such as R167 of p50^cdc37, and/or features of molecules known to bind to the ATP binding site, such as geldanamycin, radicicol, or compounds described in WO03/055860.

Having designed or selected possible binding partners, these can then be screened for activity. Thus the method may comprise the further steps of : (e) obtaining or synthesising the candidate agent compound; and (f) contacting the candidate agent compound with Hsp90 and/or a complex between p50^cdc37 and Hsp90 to determine the ability of the candidate agent compound to modulate the activity of Hsp90.

The ability of the candidate agent compound to modulate the activity of Hsp90 may be determined by measuring ATPase activity of Hsp90 or the ability of Hsp90 to modulate the quantity or activity of a client protein, which may be a kinase. The skilled person will be aware of numerous appropriate assay formats and will be well capable of designing a suitable assay protocol .

The assay may be performed in a cell-free system or in a cell culture. Hsp90 activity in cell culture can be measured by observing quantity or activity of a client protein activity e.g. measuring levels of ERK-phosphorylation, or quantity of Raf-1 or B-Raf . Additionally or alternatively, the assay may comprise determining whether an increase in expression of further heat shock-regulated proteins, such as Hsp70, occurs. Suitable methods are described in Aherne et al (2003) .

Instead of, or in addition to, performing e.g. a chemical assay, the method may comprise the further steps of:

(e) obtaining or synthesising the candidate agent compound;

(f) forming a complex between Hsp90 and the candidate agent compound and optionally p50^cdc37; and (g) analysing said complex by X-ray crystallography or NMR spectroscopy to determine the ability of the candidate agent compound to interact with Hsp90.

Detailed structural information can then be obtained about the binding of the agent compound to the complex, and in the light of this information adjustments can be made to the structure or functionality of the compound, e.g. to improve binding to the binding cavity. Steps (e) to (g) may be repeated and re- repeated as necessary. For X-ray crystallographic analysis, the complex may be formed by crystal soak-in methods or co- crystallisation.

Greer et al . describes an iterative approach to ligand design based on repeated sequences of computer modelling, protein- ligand complex formation and X-ray crystallographic or NMR spectroscopic analysis. Thus novel thymidylate synthase inhibitor series were designed de novo by Greer et al . , and Hsp90 inhibitors may also be designed in the this way. More specifically, using e.g. GRID on the solved 3D structure of the Hsp90-p50^cdc37 complex, a ligand (e.g. a potential inhibitor) may be designed that complements the functionalities of the binding site(s) . The ligand can then be synthesised, formed into a complex with Hsp90 and optionally p50^cdc37, and the complex then analysed by X-ray crystallography to identify the actual position of the bound ligand. The structure and/or functional groups of the ligand can then be adjusted, if necessary, in view of the results of the X-ray analysis, and the synthesis and analysis sequence repeated until an optimised ligand is obtained. Related approaches to structure-based drug design are also discussed in Bohacek et al . , Medicinal Research Reviews, Vol.16, (1996), 3-50.

As a result of the determination of the structure of the Hsp90-p50^cdc37 complex, more purely computational techniques for rational drug design may also be used to design Hsp90 modulators, e.g. activators or inhibitors (for an overview of these techniques see e.g. Walters et al . ) . For example, automated ligand-receptor docking programs (discussed e.g. by Jones et al . in Current Opinion in Biotechnology, Vol.6, (1995) , 652-656) which require accurate information on the atomic coordinates of target receptors may be used to design potential modulators. Linked-fragment approaches to drug design also require accurate information on the atomic coordinates of target receptors. The basic idea behind these approaches is to determine (computationally or experimentally) the binding locations of plural ligands to a target molecule, and then construct a molecular scaffold to connect the ligands together in such a way that their relative binding positions are preserved. The connected ligands thus form a potential lead compound that can be further refined using e.g. the iterative technique of Greer et al . . For a virtual linked-fragment approach see Verlinde et al., J. of Computer-Aided Molecular Design, 6, (1992) , 131-147, and for NMR and X-ray approaches see Shuker et al . , Science, 274, (1996), 1531-1534 and Stout et al . , Structure, 6, (1998), 839-848. The use of these approaches to design Hsp90 inhibitors is made possible by the determination of the structure of the Hsp90-p50^dc37 complex.

Many of the techniques and approaches to structure-based drug design described above rely at some stage on X-ray analysis to identify the binding position of a ligand in a ligand-protein complex. A common way of doing this is to perform X-ray crystallography on the complex, produce a difference Fourier electron density map, and associate a particular pattern of electron density with the ligand. However, in order to produce the map (as explained e.g. by Blundell et al . ) it is necessary to know beforehand the protein 3D structure (or at least the protein structure factors) . Therefore, determination of the Hsp90- p50^cdc37 complex structure also allows difference Fourier electron density maps of such complexes to be produced, which can greatly assist the process of rational drug design.

The approaches to structure-based drug design described above all require initial identification of possible compounds for interaction with the target bio-molecule. Sometimes these compounds are known e.g. from the research literature. When no suitable known starting compounds are known, or when novel compounds are wanted, a first stage of the drug design program may involve computer-based in silico screening of compound databases (such as the Cambridge Structural Database) with the aim of identifying compounds which interact with the binding site or sites of the target bio-molecule. Screening selections criteria may be based on pharmacokinetic properties such as metabolic stability and toxicity. However, determination of the structure of the complex allows the architecture and chemical nature of each binding site to be identified, which in turn allows the geometric and functional constraints of a descriptor for the potential inhibitor to be derived. The descriptor is, therefore, a type of virtual 3-D pharmacophore, which can also be used as selection criteria or filter for database screening.

The present invention further provides "wet" or in vitro methods of identifying modulators of Hsp90 activity. Thus in a further aspect there is provided a method for determining the ability of a candidate agent compound to modulate Hsp90 activity, comprising contacting an Hsp90 protein with p50^cdc37 and the candidate agent compound. Preferably the Hsp90 protein lacks all or substantially all of the C-terminal domain, and may lack all or substantially all of the middle (M) domain.

The Hsp90 protein may comprise or consist of the portion corresponding to amino acid residues 1 to 208 of yeast Hsp90.

The method may further comprise contacting an Hsp90 protein with the candidate agent compound in the absence of p50^cdc37.

The method may further comprise contacting a full-length, or substantially full-length Hsp90 protein having ATPase activity with the candidate agent compound and optionally p50^cdc37. This allows the effect of the candidate compound on ATPase activity to be determined. For example, interaction between Hsp90 and p50^cdc37 may be studied in vitro by labelling one with a detectable label and bringing it into contact with the other which has been immobilised on a solid support. Suitable detectable labels, especially for petidyl substances, include radioactive labels such as ³⁵S-methionine which may be incorporated into recombinantly produced peptides and polypeptides, as well as fluorescent labels which may be detected using a laser and confocal microscope, and enzyme labels which act on a substrate, typically to produce a colour change which can be detected spectrophotometrically.

Alternatively the complex formed on the solid support may be detected by labelling with an antibody directed against an epitope present on the protein which is not immobilised on the solid support. If no suitable antibody is available, a recombinantly-produced peptide or polypeptide may be expressed as a fusion protein containing an epitope against which a suitable antibody is available.

The protein which is immobilized on a solid support may be immobilized using an antibody against that protein bound to a solid support or via other technologies which are known per se, including simply coating the protein on a suitable surface, such as a well of a microtiter plate. A preferred in vitro interaction may utilise a fusion protein including glutathione-S-transferase (GST) , which may be immobilized on glutathione agarose beads .

In an in vitro assay format of the type described above a candidate agent compound can be assayed by determining its ability to affect the amount of labelled peptide or polypeptide which binds to the immobilized polypeptide.

Calorimetric methods of measuring interaction, for example those described in the Examples, may also be used to determine binding between Hsp90, the candidate binding agent, and optionally p50^odc37.

Suitable methods for ATPase inhibition screens are described in WO03067262 or in Aherne et al (2003) .

The above-described in vitro methods may be performed as an alternative to the in silico methods for identifying modulators of Hsp90, or in addition to them. For example the in vitro methods may be used to validate a candidate compound identified in silico.

The invention also extends to a compound which is identified as a modulator of Hsp90 activity by a method as described in any of the aspects of the invention described herein.

Following identification of a suitable modulator compound, it may be manufactured and/or used in the preparation, i.e. manufacture or formulation, of a composition such as a medicament, pharmaceutical composition or drug. These may be administered to individuals for treatment of an appropriate condition, e.g. inhibitors for use in the treatment of cancers where the compound is capable of inhibiting activation of a protein kinase client of Hsp90 implicated in initiation or pathogenesis of cancer.

Thus, the present invention extends in various aspects not only to a modulator as provided by the invention, but also a pharmaceutical composition, medicament, drug or other composition comprising such a modulator e.g. for treatment (which may include preventative treatment) of disease such as cancer; a method comprising administration of such a composition to a patient, e.g. for treatment of disease such as cancer; use of such a modulator in the manufacture of a composition for administration, e.g. for treatment of disease such as cancer; and a method of making a pharmaceutical composition comprising admixing such a modulator with a pharmaceutically acceptable excipient, vehicle or carrier, and optionally other ingredients.

The modulator compound may be considered to be a lead compound, which may be optimised either to improve its efficacy or potency of inhibition of Hsp90 activity, or to improve its pharmacokinetic or toxicity profile.

Thus a further aspect of the present invention provides a method for preparing a medicament, pharmaceutical composition or drug, the method comprising: identifying a Hsp90 modulator molecule by a method of any one of the other aspects of the invention disclosed herein; and formulating the modulator molecule into a pharmaceutical composition by admixture with a pharmaceutically acceptable carrier.

Also provided is a method for preparing a medicament, pharmaceutical composition or drug, the method comprising: having identified a Hsp90 modulator molecule by a method of any one of the other aspects of the invention disclosed herein, formulating the modulator molecule into a pharmaceutical composition by admixture with a pharmaceutically acceptable carrier.

The method may further comprise the step of optimising the structure of the modulator molecule for in vivo administration.

The above-described processes of the invention may be iterated in that the modified compound may itself be the basis for further compound design.

By "optimising the structure" we mean e.g. adding molecular scaffolding, adding or varying functional groups, or connecting the molecule with other molecules (e.g. using a fragment linking approach) such that the chemical structure of the modulator molecule is changed while its original modulating functionality is maintained or enhanced. Such optimisation is regularly undertaken during drug development programmes to e.g. enhance potency, promote pharmacological acceptability, increase chemical stability etc. of lead compounds .

Modification will be those conventional in the art known to the skilled medicinal chemist, and will include, for example, substitutions or removal of groups containing residues which interact with the amino acid side chain groups of Hsp90 or p50^cdc37. For example, the replacements may include the addition or removal of groups in order to decrease or increase the charge of a group in a test compound, the replacement of a charge group with a group of the opposite charge, or the replacement of a hydrophobic group with a hydrophilic group or vice versa. It will be understood that these are only examples of the type of substitutions considered by medicinal chemists in the development of new pharmaceutical compounds and other modifications may be made, depending upon the nature of the starting compound and its activity.

Compositions may be formulated for any suitable route and means of administration. Pharmaceutically acceptable carriers or diluents include those used in formulations suitable for oral, rectal, nasal, topical (including buccal and sublingual) , vaginal or parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal and epidural) administration. The formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy.

For solid compositions, conventional non-toxic solid carriers include, for example, pharmaceutical grades of mannitol, lactose, cellulose, cellulose derivatives, starch, magnesium stearate, sodium saccharin, talcum, glucose, sucrose, magnesium carbonate, and the like may be used. Liquid pharmaceutically administrable compositions can, for example, be prepared by dissolving, dispersing, etc, an active compound as defined above and optional pharmaceutical adjuvants in a carrier, such as, for example, water, saline aqueous dextrose, glycerol, ethanol, and the like, to thereby form a solution or suspension. If desired, the pharmaceutical composition to be administered may also contain minor amounts of non-toxic auxiliary substances such as wetting or emulsifying agents, pH buffering agents and the like, for example, sodium acetate, sorbitan monolaurate, triethanolamine sodium acetate, sorbitan monolaurate, triethanolamine oleate, etc. Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in this art; see for example Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pennsylvania, 19th Edition, 1995.

Percent (%) amino acid sequence identity with respect to a reference sequence is defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the reference sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. % identity values may be determined by WU-BLAST-2 (Altschul et al., Methods in Enzymology, 266:460-480 (1996)). WU-BLAST-2 uses several search parameters, most of which are set to the default values. The adjustable parameters are set with the following values: overlap span = 1, overlap fraction = 0.125, word threshold (T) = 11. A % amino acid sequence identity value is determined by the number of matching identical residues as determined by WU-BLAST-2, divided by the total number of residues of the reference sequence (gaps introduced by WU-BLAST-2 into the reference sequence to maximize the alignment score being ignored), multiplied by 100.

A residue in a first protein may be said to correspond to a residue in a second protein where those residues in the first and second proteins are directly aligned with one another when an alignment is carried out as described above.

Additionally or alternatively a residue in a first protein may be said to correspond to a residue in a second protein when those residues make equivalent interactions with a given residue in a third protein when the first and second proteins respectively are bound to that third protein (e.g. ionic bonds, electrostatic interactions such as salt bridges, hydrogen bonds, van der Waals interactions, or hydrophobic interactions) .

Preferably, in the respective complexes, the atoms from the first and second proteins responsible for the interaction with the residue of the third protein lie at a similar distance from the same atoms of the relevant residue of the third protein, e.g. +/- 1A, preferably +/- 0.5A, more preferably +/- 0.2A.

Percent (%) amino acid similarity is defined in the same way as identity, with the exception that residues scoring a positive value in the BLOSUM62 matrix are counted. Thus, residues which are non-identical but which have similar properties (e.g. as a result of conservative substitutions) are also counted.

In a similar manner, percent (%) nucleic acid sequence identity with respect to a reference nucleic acid is defined as the percentage of nucleotide residues in a candidate sequence that are identical with the nucleotide residues in the reference nucleic acid sequence. The identity values used herein may be generated by the BLASTN module of WU-BLAST-2 set to the default parameters, with overlap span and overlap fraction set to 1 and 0.125, respectively.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1. Localisation of Hsp90 - C-p50 interaction a) Schematic of the domain structure of p50^cdc37 (left) and Hsp90 (right) b) Isothermal titration calorimetry (ITC) of full-length human p₅₀_^c37 i_nj_ec ed into full length yeast Hsp90. The proteins interact with KD = 1.46 μM, with approx..l:l stoichiometry, consistent with previous observations (Siligardi et al . , 2002) . c) ITC of a C-terminal construct of p50^cdc37 (residues 138-378 : C-p50^cdc37) binding to full-length yeast Hsp90. The affinity of the interaction is very similar to that of the fulllength proteins, confirming the previous observation that Hsp90- binding was a function of C-p50^cdc37. d) ITC of C- p50^cdc37 binding to the isolated nucleotide binding domain of Hsp90 (1-220 : N-Hsp90) . The affinity of the interaction is very close to that of the full-length protein, identifying N-Hsp90 as the primary binding site for p50^cdc37. e) As d) , but with the N-terminal nucleotide-binding domain of human Hsp90α. which has 69% sequence identity to the yeast equivalent. The similar affinity demonstrates unequivocally that the interaction between C- p50^cdc37 and N-Hsp90 is authentic and universal.

Figure 2. Structure of C- p50^cdc37 a) Secondary structure cartoon of C- p50^cdc37 shaded from the visible N-terminus at residue 148 to the visible C-terminus at

347. The disordered polypeptide chain connecting residues 308 and 316 is indicated by a dotted line. b) Alignment of the sequence and structure of human p50^cdc37 with the amino acid sequences of representative p50^cdc37 homologues from amphibians {Xenopus laevis) , fish (Tetraodon fluviatilis - puffer-fish) , insects (Drosophila melanogaster) , and worms ( Caenorhabdi tis elegans) ; human Hare (Hsp90- associating relative of Cdc37 (Scholz et al . , 2001)) and Saccharomyces cerevisiae Cdc37p. The observed secondary structural elements are shown above the sequence. The yeast

Cdc37p sequence beyond residue 120 is extremely diverged with several substantial relative insertions, and cannot be aligned reliably. The alignment shown here is based on optimal sequence threading (Jones et al . , 1992) of the Cdc37p sequence on the C- p50^cdc37 structure, and may be more accurate than a purely sequence-based alignment, but should be regarded with suspicion. The 'zigzag' over the N-terminal protein kinase- binding region of the p50^cdc37 sequence indicates a predicted -70 residue coiled-coil segment. Residues involved in Cp50^cdc37 dimerisation are enclosed in boxes with a dotted fill; those involved in interaction with Hsp90 are enlosed in boxes with a hatched fill.

Figure 3. C-p50^cdc37 dimer a) Secondary structure cartoon of C-p50^cdc37 dimer (one monomer is coloured cyan, the other green) . b) As a) but rotated around the vertical. c) As a) but rotated about the horizontal. The dimer is shown as molecular surfaces on the right. The C-p50^cdc37 dimer exists in solution with a KD approx ., 170μM and dimer formation buries -560 A² of molecular surface. d) Details of the interactions in the C-p50^cdc37 dimer interface . Hydrogen bonds are indicated by broken rods connecting interacting atoms.

Figure 4. Hsp90-p50 interaction a) Secondary structure cartoon of the N-Hsp90 - C-p50^odc37 complex (rainbow coloured as in Figure 2a) superimposed on the molecular surfaces of the two proteins (C p50^cdc37 cyan, N-Hsp90 gold) . b) Details of the interactions between N-Hsp90 (gold side- chain carbons and labels) and C-p50^cdc37 (cyan side-chain carbons and labels) . The interface primarily involves Hsp90 residues exposed on the face of the 'lid' segment (residues 100-121) in free N-Hsp90 structures, and residues from the loop between the first two helices and the beginning of the third helix, in the C-p50^cdc37 structure. Ala 107 (underlined) from Hsp90 is fully exposed in free N-Hsp90 structures, and its mutation to asparagine has previously been shown to enhance the ATPase activity of Hsp90 (Prodromou et al . , 2000) by favouring lid closure on ATP binding, and promoting N- terminal association in the Hsp90 dimer. In the complex Ala 107 is buried in the core of the hydrophobic interface with C- p50^cdc37, which would be completely disrupted by the presence of the larger hydrophilic residues such as asparagine. c) ATPase activity of wild-type and mutant Hsp90s (see METHODS) , in the presence of increasing amounts of C-p50^cdc37. Compared to wild-type, the A107N mutant Hsp90 is effectively resistant to ATPase arrest by C-p50^cdc37. A second hyperactive Hsp90 mutant T22I retains full sensitivity to by C-p50^cdc37. d) ITC of C-p50^cdo37 binding to wild-type or A107N Hsp90. While the wild-type chaperone interacts with micro olar affinity, there is no detectable binding to the A107N mutant, consistent with the disruption of the interface this mutation would cause.

Figure 5. Pocket and Lid interactions a) Model of ADP bound to N-Hsp90 in the presence of C-p50^cdc37, generated by superimposing N-Hsp90 from the previously described N-Hsp90 - ADP complex (Prodromou et al . , 1997a) onto the N-Hsp90 in this complex. Arg 167 of C-p50^cdc37 inserts its side-chain into the mouth of the nucleotide-binding pocket of Hsp90, hydrogen bonding with the carboxylate side-chain of the catalytic residue Glu 33, and with its guanidinium head-group occupying the position expected for the attacking water in the ATPase reaction. The key adenine-binding residue, Asp 79, is indicated. b) Model of geldanamycin (GD) bound to N-Hsp90 in the presence of C-p50^cdc37, generated by superimposing N-Hsp90 from the previously described N-Hsp90 - GD complex (Roe et al . , 1999) onto the N-Hsp90 in this complex. Consistent with biochemical observations (Siligardi et al . , 2002; Shao et al . , 2001) the presence of Arg 167 would not be expected to interfere with geldanamycin binding, however it would certainly alter the chemical environment of the mouth of the pocket, and in vivo could selectively limit or enhance binding of larger Hsp90 inhibitors . c) Superimposition of N-Hsp90 structure in the p50^dc37 complex (gold Ca trace) on the N-Hsp90 structure from the ADP-complex. Binding of C-p50^cdc37 (cyan cartoon) lifts the lid away from the body of the structure, and causes a rearrangement of residues 96-99. d) As C) but viewed towards the nucleotide-binding pocket. Lifting of the lid imposes a helical conformation on residues 96-99, causing the tip of the side-chain of Lys 98 to move by > 12A.

Figure 6. Architecture of the Hsp90 - p50^cdc37 complex a) Secondary structure cartoon of the (N-Hsp90)₂ - (C- p50^cdc37)₂ complex. The crystal asymmetric unit contains one N-Hsp90 - C- p₅₀ ^cd_³⁷ hetero-dimer, and the complete hetero-tetramer is formed by the homo-dimerisation of two crystallographically related C-p50^cdc37 molecules (cyan/green) . N-Hsp90 is shown in gold. The positions of the N-terminus of C-p50^cdc37 and the C- terminus of N-Hsp90 are indicated. b) As A) but viewed from the opposite side to the long helical protrusions of C-p50^cdc37. The N-termini of both C-p50^cdc37 molecules and the C-termini of both N-Hsp90s are on this face. c) Hypothetical model of a complete Hsp90 - p50^cdc37 - client protein kinase complex. The bottom of the structure is the observed (N-Hsp90)₂ - (C-p50^cdc37) ₂ heterotetramer, described here . The known crystal structure of the middle domain of Hsp90 (Meyer et al . , 2003) has been positioned so that its N- terminus is within δA of the C-terminus of N-Hsp90. The structure of the C-terminal constitutive dimerisation domain of Hsp90 has not yet been described, and is represented by a pair of cylinders. Although the structure of the N-terminal domain of p50^cdc37 is also unknown, it predicts strongly as a substantial coiled-coil, and in this model is represented by a coiled-coil of comparable length, from seryl-tRNA synthetase (PDB Code 1SET) , docked to connect with the N-terminus of the observed C-p50^cdc37. Finally, the structure of a known client protein kinase, Cdk6 (PDB Code 1BI7) (pink molecular surface) was docked between the two Hsp90 middle segments and the modelled p50^cdc37 N-terminal coiled-coil, so as to minimise steric clashes while contacting residues from the middle segment implicated in interaction with client proteins (Sato et al., 2000; Fontana et al . , 2002; Meyer et al . , 2003).

The invention will now be described with reference to specific examples which are exemplary and for illustrative purposes only. They are not intended to be limiting in any way to the scope of the invention described.

RESULTS AND DISCUSSION

Localising the Hsp90 - p50^cdc37 Interaction Previous studies of co-chaperone interactions with Hsp90 had shown mutually exclusive binding of p50^cdc37 and TPR-do ain co- chaperones such as Hop/Stil (Owens-Grillo et al . , 1996) which has been generally interpreted in terms of competitive binding by p50^cdc37 at or close to the known TPR-binding site at the C- terminus of Hsp90. However there was some ambiguity in this assignment, as although p50^cdc37 binding was competed by full length TPR-domain co-chaperones, an isolated TPR-domain could bind simultaneously with p50^cdc37 (Silverstein et al . , 1998). To resolve this question, we analysed the interaction between p50^cdc37 or a C-terminal segment of p50^cdc37 (C-p50^cdc37 : residues 138-378) previously shown to be sufficient for Hsp90 binding (Shao et al . , 2001; Siligardi et al . , 2002), and a set of yeast Hsp90 constructs, using isothermal titration calorimetry (ITC) (FIGURE 1) . As expected from previous studies using difference CD (Siligardi et al., 2002), full-length p50^cdc37 and C-p50^cdc37 bound to full-length Hsp90 with very similar affinities (KD = 1.46 μM, and 1.32 μM, respectively). However, no significant heats of interaction were observed with any Hsp90 construct lacking the N-terminal nucleotide binding domain, regardless of the presence or absence of the C- terminal constitutive dimerisation domain. Consistent with these observations the isolated nucleotide-binding domain bound to C-p50^cdc37 with comparable affinity to full length Hsp90 (KD = 1.80 μM), identifying it unambiguously as the primary binding site for p50^cdc37. Although Hsp90s are extremely highly conserved especially in the N-terminal domain, we, were concerned to verify that this interaction was not an artefact of yeast Hsp90 binding to human p50^cdc3?. In confirmation of this we found that the N-terminal domain of human Hsp90 . bound to C-p50^cdc37 with comparable affinity (Kd = 3.37 μM) . In all cases p50cdc37 constructs and Hsp90 constructs formed complexes with 1:1 stoichiometry.

On the basis of this observation, crystallisation screens were conducted with equimolar mixtures of C- p50cdc37 and various Hsp90 N-terminal domain constructs. Diffraction quality crystals were obtained in several conditions using human C- p50cdc37 and yeast Hsp90 (1-208) . The structure was phased by molecular replacement using the known structure of the yeast Hsp90 N-terminal domain (N-Hsp90) (Prodromou et al . , 1997b; Prodromou et al . , 1997a) as a search model. The structure of C-p50 cdc37 was determined from difference Fourier maps and the structure of the complex refined at 2.4A (see METHODS) .

Structure of C-p50^cdc37

The C-terminal segment of p50^cdc37 is entirely helical in structure, consisting of a large 6-helix bundle at the N- terminal end of the visible structure (residues 148-245) connected to a small 3-helix bundle (292-347) via a long single helix (246-286) . This small helical bundle is less well ordered than the rest of C-p50^cdc37 and no interpretable electron density is present for residues 309-315 which connect the first and second helices of this domain. The large helical domain has an unusual topology, with helices 2-5 forming a right-handed orthogonal 4-helix bundle while helix 6 and the proximal part of the long connecting helix form an c-arch that wraps around the surface of helix 5 (FIGURE 2A) . Comparison of C p50^cdc37 with libraries of known protein folds yielded no structure of comparable topology (Pearl et al . , 2000; Murzin et al . , 1995). The sequence of this region is reasonably conserved in vertebrates becoming more diverged in invertebrates and fungi (FIGURE 2B) . Nontheless, optimal sequence threading (Jones et al . , 1992) of the highly diverged S. cerevisiae Cdc37p sequence unambiguously recognises the large globular domain of p50^cdc37 as the best fit, suggesting that despite sequence variation the overall fold is universally conserved. In the crystals, C-p50^cdc37 forms a homo- dimeric interaction with a symmetry related molecule (FIGURE 3A,B,C). The core of the interface involves close packing of the main chain and side chains of Gin 247 and Tyr 248, in the first turn of the long connecting helix, with their equivalents in the other monomer. This hydrophobic core interaction is reinforced by ion-pairs between Lys 240 and Asp 245 from separate monomers, a carboxyl-carboxylate interaction between the side chains of Asp 294 from each monomer, and a network of hydrogen bonding involving the side chains of Arg 246 and Glu 250 from one monomer with Glu 221 and Glu 255 from the other (FIGURE 3D) . Previous studies showed that full- length p50^cdc37 is a dimer in solution with a KD approx. 5-10 μM (Siligardi et al . , 2002). The isolated C-terminal domain of p₅₀_^c37 _retains the ability to dimerise but with reduced affinity (KD approx.170 μM) . However at the concentrations used in crystallisation experiments and in the presence of the molecular crowding agents used to promote crystallisation, C- p₅Q^cdc37 _woui^ be predominantly dimeric so that the dimer observed in the crystals is likely to be authentic. The relatively small surface area buried in that interface (560 A²) would be consistent with the measured affinity.

Hsp90 - p50^cdc37 Interactions

The Hsp90 N-terminal nucleotide-binding domain binds to the large helical domain of C-p50^cdc3?, with helices 2, 3 and 5 from C-p50^cdc37 packing against the surface of the 'lid' segment in N-Hsp90 (residues 100-121) , which is thought to close over bound ATP (Prodromou et al . , 2000) (FIGURE 4A) . The core of the interaction involves a relatively flat hydrophobic patch formed by the side-chains of Met 164, Leu 165, Ala 204 and Leu 205 of p50^cdc37, which pack against a similar patch formed by the side chains of Ala 103, Ala 107, AlallO, Gly 111, Ala 112, Met 116 and Phe 120 of Hsp90. The central hydrophobic interface is reinforced by a network of polar interactions including several inter-molecular side-chain to main-chain hydrogen bonds. The most substantial part of this network involves Gin 119 of Hsp90 whose main-chain oxygen is hydrogen bonded to the side chain of Gin 208 of p50^cdc37, while its side chain hydrogen bonds to the main-chain carbonyl of Asp 120 and the main-chain nitrogens of Arg 166 and Arg 167 of p50^cdc37 (FIGURE 4B) . The interaction of Hsp90 and p50^cdc37 buries approx. 1056 A² of molecular surface. Although the Hsp90 N- terminal domain used in this study derives from yeast, all the residues in contact with p50^cdc37 are identical to those in both of the human cytoplasmic Hsp90 isoforms, with the exception of Ser 109 on the edge of the lid, which hydrogen bonds to the side-chain of p50^cdc37 Lys 202 - an interaction available to the glutamine found at this position in human Hsp90s.

We have previously described a mutation engineered in the surface of the lid segment, A107N, which activates the inherent ATPase of Hsp90 probably by favouring lid closure and N-terminal association on binding of ATP (Prodromou et al . , 2000) . As Ala 107 is intimately involved in the close-packed hydrophobic interface with p50^cdc37 observed in these crystals, its mutation to a larger hydrophilic residue would be expected to have a very substantial impact if that is indeed the functional interface between the two proteins . We therefore analysed the effect of the A107N mutation on interaction of

Hsp90 with p50^cdc37 in solution. In marked contrast to the wild- type, the ATPase activity of the Hsp90- A107N mutant was completely resistant to inhibition by p50^cdc37. We also examined the sensitivity of a second Hsp90 mutant, T22I, which like A107N has a substantially enhanced inherent ATPase activity (Prodromou et al . , 2000), but unlike Ala 107, Thr 22 is not involved in the observed interface with p50^cdc37. In this case the ATPase activity was fully sensitive to inhibition by p50^cdc37, showing that the desensitisation produced by the A107N mutation is specific and not a general property of hyperactive Hsp90 mutants. Consistent with its effect on ATPase inhibition, and in contrast to wild-type, no significant heat was generated when p50^cdc37 was titrated into Hsp90-A107N in ITC experiments (FIGURE 4C,D) .

The side-chain of Arg 167 from p50^cdc37 points down into the mouth of the nucleotide binding pocket in the Hsp90 N-terminal domain and hydrogen bonds to the carboxyl sidechain of Glu 33 (FIGURE 5A) . This residue is believed to act as the general base in the chaperone' s ATPase reaction (Prodromou et al . , 1997a; Panaretou et al . , 1998; Obermann et al . , 1998), and the guanidinium group of Arg 167 occupies the position expected for the attacking nucleophilic water. Arg 167 does not penetrate deeply enough into the pocket to obstruct binding of nucleotides or drugs such as geldanamycin (FIGURE 5B) . This is consistent with previous experimental observations that binding of p50^cdc37 does not displace geldanamycin from Hsp90 (Siligardi et al . , 2002) and that geldanamycin does not disrupt Hsp90-p50^cdc37 complexes (Shao et al . , 2001). Nonetheless, the presence of the side-chain of Arg 167 does alter the electronic and chemical environment at the top of the pocket, so that novel Hsp90 inhibitors that impinge upon this part of the pocket could be tailored to bind selectively to, or be selectively excluded from, Hsp90-p50^cdc37 complexes. Binding of p50^cdc37 elicits some small but potentially significant conformational changes in the N-terminal domain of Hsp90 compared to the structures of the free or nucleotide bound domain. The lid segment, which provides the majority of the interaction with p50^cdc37, moves away from the rest of the domain, hinging at glycines 100 and 121, with the tip of the lid moving by more than 3 A compared to the structures in the absence of p50^cdc37 (PDB codes 1AH6, 1AMW) (FIGURE 5C) . Accompanying the lid movement, is a substantial restructuring of the backbone between Leu 93 and Gly 100 which takes on an α-helical conformation, extending the helix from 101 to 109 in the free structure by nearly two turns at its N-terminus and the helix from 86-92 by a turn at its C-terminus. This change in backbone conformation causes substantial movement in the side chains of lie 96, Ala 97 and particularly Lys 98 whose side-chain e -amino group is flipped by > 12A away from the ATP-binding pocket, where it interacts with the /.-phosphate of bound nucleotides (Prodromou et al . , 1997a), and out into the solvent (FIGURE 5D) . This segment of the polypeptide chain displays two alternative conformations in human Hsp90 N- terminal domain structures (Stebbins et al . , 1997), however this helical conformation observed in the presence of p50^cdc37 is substantially different from either of those.

Architecture of the Hsp90 - p50^cdc37 Complex

Within the crystals the C-p50^cdc37 dimer sits between two symmetry related Hsp90 N-terminal domains, which are orientated so that the open mouths of their nucleotide-binding pockets are facing each other, but > 4θA apart. The large globular domain of the C-p50^cdo37 molecules forming the dimer, and the two bound Hsp90 N-terminal domains lie in a plane, with the long helix and small C-terminal helical bundle from each of the C-p50^cdc37 molecules projecting > 5θA from one face of the plane (FIGURE 6A,B) . Hsp90 functions as a dimer, with a high-affinity constitutive dimerisation interface provided by the C-terminal regions (Nemoto et al . , 1995) and an ATP- dependent interface involving the N-terminal domains (Prodromou et al . , 2000; Chadli et al . , 2000; Wegele et al . ,

2003) . Hsp90 and p50^{c c37} interact as dimers with 1:1 molar stoichiometry, and part of the p50^cdc37 dimerisation interface is provided by the Hsp90-binding C-terminal region of p50^cdc37 present in the structure described here (Siligardi et al . , 2002) . All the interactions observed between Hsp90 and p50^cdc37 and within the p50^cdc37 dimer are provided by the large globular domain of the C-p50^cdc37 structure consistent with the observation in yeast Cdc37p that regions C-terminal to this are dispensable for normal function in vivo (Lee et al . , 2002) . Taken together all these data suggest that the complex of the N-Hsp90 and C-p50^cdc37 domains described here is a true representation of the interaction of these regions of the two molecules within the full (Hsp90) ₂- (p50^cdc37) ₂ hetero-tetramer complex. In Hsp90, the N-terminal domain is followed by a middle segment, consisting of two -.jSc* domains connected by a short helical supercoil (Meyer et al . , 2003), which is directly implicated in interactions with several client proteins, including protein kinases (Sato et al.,2000; Fontana et al . , 2002) . From the position of the C-terminus of the Hsp90 N-domain in the complex described here, the middle and C-terminal segments in the intact Hsp90 dimer would have to be on the opposite side of the plane (see above) to the projecting helical segments of p50^cdc37. The structure of the N- terminal kinase-binding domain of p50^cdc37 is as yet unknown, although structure prediction suggests it has a substantial coiled-coil content. From a similar consideration of the position of the N-terminus of C-p50^cdc37, whatever its structure the N-terminal domain is also likely to be directed in the opposite direction to the helical protrusions and in the same direction as the middle segment of Hsp90, suggesting an overall head-to-tail interaction between Hsp90 and p50^cdc37. This arrangement would allow simultaneous interaction of a client protein kinase with the middle segment of Hsp90, and with the N-terminal domain of p50^cdc37 (FIGURE 6C) .

Mechanism of Hsp90 ATPase arrest by p50^dc37 The combination of the constitutive C-terminal interface and the ATP-dependent association of the N-terminal domains, generates a molecular clamp, whose opening and closing is coupled to the ATPase activity of the chaperone (Prodromou et al . , 2000) . Although it has not yet been observed directly, substantial evidence from biochemical studies (Prodromou et al., 2000; Richter et al . , 2001; Richter et al . , 2002) and analogy with related dimeric GHKL-family ATPases (Dutta and Inouye, 2000) suggests that the N-terminal domains in the Hsp90 dimer must come into direct contact for ATP hydrolysis to take place. Dimerisation of the N-terminal domains within the dimer is believed to be driven by self-association of a hydrophobic surface, exposed when the 'lid' segment closes over bound ATP (Prodromou et al . , 1997a; Prodromou et al . , 2000) , reinforced by interactions involving the first strand of the N-domain (Richter et al . , 2002). However, dimerisation of the N-terminal domains while necessary is not sufficient, and the middle segment of Hsp90 from each monomer must contribute additional catalytic residue (s), for ATP-hydrolysis to occur (Soti et al . , 2002; Meyer et al . , 2003).

From the complex described here, it is evident that p50^cdc37 achieves its inhibitory effect on the Hsp90 ATPase cycle by interfering with several key points in the chain of events that permits ATP-hydrolysis. Firstly, p50^cdc37 chemically disables nucleophilic attack on the β-y phosphoester bond of ATP by inserting the side-chain of Arg 167 into the mouth of the nucleotide-binding pocket, where it hydrogen bonds' to and neutralises the general base Glu 33, and occupies the probable site of the attacking water molecule. Secondly, it binds to the open face of the lid segment in the N-domain of Hsp90, simultaneously preventing its closure over bound ATP and blocking access by the middle segment which provides the 'missing' catalytic residue (s) needed to orientate and polarise the γ-phosphate. Thirdly, the p50^cdc37 dimer sits between the two N-domains of the Hsp90 clamp, holding them open like a brace and preventing their trans-activating interaction.

An ability to arrest the Hsp90 ATPase cycle is shared by p₅₀-^d-³⁷ _and Hop/Stil (Prodromou et al . , 1999; Siligardi et al . , 2002) , both of which are 'early' co-chaperones involved in recruitment of client proteins to the Hsp90 machinery. How Hop/Stil inhibits Hsp90 is not yet described. p50^cdc37 holds Hsp90 in an 'open' conformation in which the putative binding surfaces in the middle segment of the chaperone (Fontana et al., 2002; Sato et al . , 2000; Meyer et al . , 2003) would be accessible to a client protein kinase bound to the N-terminal domain of p50^cdc37. Progress from this arrested 'loading' phase through the ATPase cycle would absolutely depend on ejection of the p50^cdc37 C-terminus from between the jaws of the Hsp90 clamp to allow it to close. However p50^cdc37 could remain persistently associated with the cycling Hsp90 complex via the interaction of its N-terminus with the bound client protein kinase. The rate with which the arrested Hsp90- p50^cdc37 complex converts to a cycling complex will undoubtedly be affected by other cochaperones such as Ahal, immunophilins and p23/Sbal, whose binding influences the Hsp90 ATPase cycle (Panaretou et al., 2002; Lotz et al . , 2003; Young and Hartl, 2000).

However, it is also likely to depend on the nature and affinity of the interaction of the client protein itself with Hsp90, communicated via the N-terminal kinase-binding domain of p50^cdc37 to its inhibitory C-terminus.

METHODS

Expression and Purification of Proteins

Native and mutant yeast Hsp90 constructs, or human p50^cdc37 constructs, were inserted with N-terminal His₆-tag into pRSETA and expressed in E. coli BL21(DE3) pLysS as previously described (Prodromou et al . , 2000; Siligardi et al . , 2002; Meyer et al . , 2003) . In all cases expressed proteins were purified by metal affinity chromatography on Talon resin, ion- exchange on Q-sepharose, and size-exclusion chromatography on a Superdex 75 PG or Sephacryl 400 HR column equilibrated in 20 mM Tris pH 7.5, 150 mM NaCl , 1 mM EDTA and 0.5 mM DTT (buffer A) . Fractions containing pure cleaved proteins were dialysed against buffer A and finally concentrated using 5K Vivaspin concentrators. Purified human Hsp90α N-terminal domain was a kind gift from Dr. Adam Collier, British Biotechnology, Cambridge U.K. Isothermal titration calorimetry and ATPase assays.

Heats of interaction between Hsp90 and p50^cdc37 constructs were measured on a MSC system (Microcal Inc.) . 15 aliquots of 20 μl C-p50^cdc37 (250 μM) were injected into 1.458 ml of 25 μM Hsp90 construct at 30°C in 40 mM Tris pH 8.0 containing 1 mM EDTA and 5 mM NaCl . For the full-length proteins p50^cdc37 was injected at 324 μM into Hsp90 at 32.4 μM. Heats of dilution were determined in a separate experiment by diluting protein in buffer, and the corrected data were fitted using a non- linear least square curve-fitting algorithm (Microcal Origin) with three floating variables: stoichiometry, binding constant and change of enthalpy of interaction.

Hsp90 ATPase activity and its inhibition by p50^cdc37 was measured using an enzyme linked assay as previously described (Panaretou et al . , 1998; Prodromou et al . , 1999; Siligardi et al . , 2002) . Wild-type and mutant Hsp90s were used at 2μM, and p_5Q ^cdc37 constructs in a range from 0.5 to 16 μM. All data were corrected for geldanamycin-resistant background as previously described.

Crystallisation, data collection and structure determination.

After initial screens to identify promising conditions, diffraction quality crystals of the complex were grown from a mixture of N-Hsp90 and C-p50 at a final concentration of 0.5mM and 0.4mM respectively, in a solution containing 12% polyethylene glycol 4000, 16% isopropanol and lOOmM sodium citrate, pH 6.0. Crystal drops were set up using the hanging- drop vapour diffusion method, initially at 4°C for 48 hours and then transferred to 14°C. Complex crystals were cryoprotected in crystallisation buffer with the addition of 25% glycerol and were flash cooled in liquid nitrogen. Crystals belonged to space group P3121 (or its enantiomorph) with unit cell dimensions a = 83.76A, c = 148.45A. Analysis of the Matthews coefficient suggests a solvent content of 60%, with one molecule each of NHsp90 and C-p50 in the asymmetric unit. Diffraction data were collected on beamline ID14.4 at the ESRF Grenoble, and images processed and data reduced using MOSFLM (Leslie, 1995) and SCALA (CCP4, 1994) . A clear molecular replacement solution in P3121 was found using the program Molrep (Vagin and Teplyakov, 2000) , with the structure of the N-terminal domain of yeast Hsp90 as a search model (PDB code 1AMW) . The top solution gave a correlation coefficient of 0.363 and an R-factor of 0.515 for one N-terminal HSP90 molecule in the asymmetric unit. The electron density map generated from the molecular replacement solution was of a high quality and density corresponding to the Cp50 component of the complex was clearly visible. ARP-wARP (Lamzin and Wilson, 1997) was used initially for auto-tracing of the main chain polypeptide and subsequent building was preformed manually in O (Jones et al . , 1991) . Refmac (Murshudov et al., 1997) was used for structure refinement. Statistics for the crystallographic data collection and refinement are given in Table 1. All molecular graphics images were generated using PyMol (DeLano, 2002) .

Coordinates and structure factors for the refined complex have been deposited in the Protein Database with PDB code: 1US7.

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Data Collection overall (outer shell)

Resolution limit (A) 2.4 Observations 26462 Completeness (%) 96.4 (96.4) Multiplicity 3.6

■ -sym 0.063 (0.284) i/σl 15.2 (4.0)

Refinement

Resolution range (A) 72.5 - 2.4 No. reflections 25125 No . of protein atoms 3414 No . of solvent atoms 176

• cryst 0.185

Rfre_e (5% data) 0.240 <B> (A²) 38.1

Table 2. Crystallographic coordinate data

HEADER XX-XXX-XX COMPND REMARK REMARK REFINEMENT. REMARK PROGRAM REFMAC 5.1.24 REMARK AUTHORS MURSHUDOV, VAGIN, DODSON REMARK REMARK REFINEMENT TARGET : MAXIMUM LIKELIHOOD REMARK REMARK DATA USED IN REFINEMENT. REMARK RESOLUTION RANGE HIGH (ANGSTROMS) 2.30 REMARK RESOLUTION RANGE LOW (ANGSTROMS) 72.55 REMARK DATA CUTOFF (SIGMA (F) ) NONE REMARK COMPLETENESS FOR RANGE (%) 96.35 REMARK NUMBER OF REFLECTIONS 25125 REMARK REMARK FIT TO DATA USED IN REFINEMENT. REMARK CROSS-VALIDATION METHOD THROUGHOUT REMARK FREE R VALUE TEST SET SELECTION RANDOM REMARK R VALUE (WORKING + TEST SET) 0.19683 REMARK R VALUE (WORKING SET) 0.19344 REMARK FREE R VALUE 0.26487 REMARK FREE R VALUE TEST SET SIZE (%) 5.0 REMARK FREE R VALUE TEST SET COUNT 1333 REMARK REMARK FIT IN THE HIGHEST RESOLUTION BIN. REMARK TOTAL NUMBER OF BINS USED 20 REMARK BIN RESOLUTION RANGE HIGH 2.300 REMARK BIN RESOLUTION RANGE LOW 2.3S0 REMARK REFLECTION IN BIN (WORKING SET) 1839 REMARK BIN R VALUE (WORKING SET) 0.242 REMARK BIN FREE R VALUE SET COUNT 91 REMARK BIN FREE R VALUE 0.387 REMARK REMARK NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT. REMARK ALL ATOMS : 3418 REMARK REMARK B VALUES. REMARK FROM WILSON PLOT (A**2) NULL REMARK MEAN B VALUE (OVERALL, A**2) 50.573 REMARK OVERALL ANISOTROPIC B VALUE. REMARK Bll (A**2) -0.57 REMARK B22 (A**2) -0.57 REMARK B33 (A**2) 0.86 REMARK B12 (A**2) -0.29 REMARK B13 (A**2) 0.00 REMARK B23 (A**2) 0.00 REMARK REMARK ESTIMATED OVERALL COORDINATE ERROR. REMARK ESU BASED ON R VALUE (A) 0 .250 REMARK ESU BASED ON FREE R VALUE (A) 0 . 231 REMARK ESU BASED ON MAXIMUM LIKELIHOOD (A) 0 .142 REMARK ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2) 5 . 873 REMARK REMARK CORRELATION COEFFICIENTS . REMARK CORRELATION COEFFICIENT FO-FC : 0.950 REMARK CORRELATION COEFFICIENT FO-FC FREE : 0.918 REMARK REMARK RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT REMARK BOND LENGTHS REFINED ATOMS (A) 3292 0.033 0 022 REMARK BOND ANGLES REFINED ATOMS (DEGREES) 4423 2.383 1 966 REMARK TORSION ANGLES, PERIOD 1 (DEGREES) 396 8.256 5 000 REMARK CHIRAL-CENTER RESTRAINTS (A**3) 487 0.186 0 200 REMARK GENERAL PLANES REFINED ATOMS (A) 2451 012 0 020 REMARK NON-BONDED CONTACTS REFINED ATOMS (A) 1487 246 0 200 REMARK H-BOND (X...Y) REFINED ATOMS (A) 178 196 0 200 REMARK SYMMETRY VDW REFINED ATOMS (A) 46 304 0 200 REMARK SYMMETRY H-BOND REFINED ATOMS (A) 12 295 0 200 REMARK REMARK ISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT REMARK MAIN-CHAIN BOND REFINED ATOMS (A**2) : 1986 ; 1 . 536 1 . 500 REMARK MAIN-CHAIN ANGLE REFINED ATOMS (A**2) : 3205 ; 2 . 770 2 . 000 REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2) : 1306 ; 4.438 ; 3 000

REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2) : 1218 ; 7.144 ; 4 500

REMARK 3

REMARK 3 NCS RESTRAINTS STATISTICS

REMARK 3 NUMBER OF NCS GROUPS : NULL

REMARK 3

REMARK 3

REMARK 3 TLS DETAILS

REMARK 3 NUMBER OF TLS GROUPS : NULL

REMARK 3

REMARK 3

REMARK 3 BULK SOLVENT MODELLING.

REMARK 3 METHOD USED : BABINET MODEL WITH MASK

REMARK 3 PARAMETERS FOR MASK CALCULATION

REMARK 3 VDW PROBE RADIUS : 1. 40

REMARK 3 ION PROBE RADIUS : 0. 80

REMARK 3 SHRINKAGE RADIUS : 0. 80

REMARK 3

REMARK 3 OTHER REFINEMENT REMARKS: (TOLL

REMARK 3

LINK CYS B 308 MET B 316 gap

CRYST1 83 759 83 759 148.445 90. 00 90.00 120.00 P 31 2 1

SCALE1 0.011939 0.006893 0.000000 0. DO0O0

SCALE2 0.000000 0.013786 0.000000 0. DOOO0

SCALE3 0.000000 0.000000 0.006736 0. D0000

HELIX 1 1 ALA A 10 ASN A 21 1 12

HELIX 2 2 LYS A 27 LEU A 50 5 24

HELIX 3 3 PRO A 53 THR A 58 5 6

HELIX 4 4 LYS A 86 GLY A 94 1 9

HELIX 5 5 ILE A 96 ALA A 110 5 15

HELIX 6 6 VAL A 114 PHE A 120 5 7

HELIX 7 7 GLY A 123 LEU A 129 5 7

HELIX 8 8 ASP A 179 LEU A 185 5 7

HELIX 9 9 GLU A 187 SER A 198 1 12

HELIX 10 10 LYS B 149 MET B 164 1 16

HELIX 11 11 TRP B 168 LEU B 181 1 14

HELIX 12 12 GLU B 184 VAL B 199 1 IS

HELIX 13 13 CYS B 203 SER B 225 1 23

HELIX 14 14 PRO B 230 ALA B 232 5 3

HELIX 15 15 PHE B 234 THR B 243 1 10

HELIX 16 16 ARG B 246 ARG B 286 1 41

HELIX 17 17 PRO B 294 SER B 300 1 7

HELIX 18 18 LEU B 317 SER B 322 1 6

HELIX 19 19 ASP B 328 SER B 339 1 12

SHEET 1 A 7 GLU A 4 GLU A 7 0

SHEET 2 A 7 SER A 155 LEU A 160 -1 N VAL A 158 O GLU A 4

SHEET 3 A 7 GLN A 145 SER A 150 -1 N GLU A 149 O THR A 157

SHEET 4 A 7 ALA A 131 LYS A 139 -1 N SER A 138 O TYR A 146

SHEET 5 A 7 GLY A 170 LEU A 177 -1 N PHE A 176 O ASP A 132

SHEET 6 A 7 VAL A 74 ASP A 79 -1 N ASP A 79 O THR A 171

SHEET 7 A 7 ILE A 64 LYS A 69 -1 N LYS A 69 O VAL A 74

ATOM 1 N ALA A 2 37.021 66.244 19 553 1.00 63 25 N

ATOM 2 CA ALA A 2 35.888 66.191 18 552 1.00 62 70 C

ATOM 3 CB ALA A 2 35.219 67.601 18 335 1.00 62 82 C

ATOM 4 C ALA A 2 36.436 65.614 17 217 1.00 62 08 C

ATOM 5 O ALA A 2 36.504 66.298 16 181 1.00 63 82 O

ATOM 6 N SER A 3 36.819 64.349 17 227 1.00 57 95 N

ATOM 7 CA SER A 3 37.359 63.813 16 029 1.00 55 43 C

ATOM 8 CB SER A 3 38.296 62.716 16 397 1.00 54 10 C

ATOM 9 OG SER A 3 37.580 61.527 16 346 1.00 58 11 0

ATOM 10 C SER A 3 36.293 63.321 14 969 1.00 53 32 c

ATOM 11 O SER A 3 35.410 62.571 15 319 1.00 55 51 0

ATOM 12 N GLU A 4 36.469 63.648 13 694 1.00 47 86 N

ATOM 13 CA GLU A 4 35.593 63.245 12 596 1.00 45 78 C

ATOM 14 CB GLU A 4 35.555 64.389 11 605 1.00 43 87 C

ATOM 15 CG GLU A 4 35.251 65.721 12 277 1.00 48 84 C

ATOM 16 CD GLU A 4 34.961 66.784 11 235 1.00 53 89 C

ATOM 17 OE1 GLU A 4 33.984 66.587 10 441 1.00 56 01 O

ATOM 18 OE2 GLU A 4 35.719 67.786 11 231 1.00 50 79 O

ATOM 19 C GLU A 4 36.029 62.002 11 805 1.00 43 88 c

ATOM 20 O GLU A 4 37.221 61.778 11 525 1.00 43 75 0

ATOM 21 N THR A 5 35.052 61.252 11 364 1.00 40 89 N

ATOM 22 CA THR A 5 35.232 59.988 10 694 1.00 39 60 C

ATOM 23 CB THR A 5 34.510 58.898 11 499 1.00 38 99 C

ATOM 24 OG1 THR A 5 35.247 58.755 12 689 1.00 43 77 0

ATOM 25 CG2 THR A 5 34.626 57.439 10 919 1.00 35 80 C

ATOM 26 C THR A 5 34.636 60.100 9 305 1.00 38 06 C ATOM 27 O THR A 5 33.547 60.574 9.192 1.00 34.42 o

ATOM 28 N PHE A 6 35 .402 59 .664 8 .277 1 .00 36 .50 N

ATOM 29 CA PHE A 6 34 .982 59 .639 6 .850 1 .00 33 .93 C

ATOM 30 CB PHE A 6 35 .632 60 .770 6 .063 1 .00 32 .20 C

ATOM 31 CG PHE A 6 35 .381 62 .150 6 .652 1 .00 31 .94 C

ATOM 32 CD1 PHE A 6 36 .336 62 .769 7 .458 1 .00 31 .48 C

ATOM 33 CE1 PHE A 6 36 .128 64 .061 7 .988 1 .00 31 .76 C

ATOM 34 CZ PHE A 6 34 .970 64 .711 7 .731 1 .00 29 .77 C

ATOM 35 CE2 PHE A 6 34 .012 64 .090 6 .925 1 .00 32 .19 C

ATOM 36 CD2 PHE A 6 34 .209 62 .839 6 .385 1 .00 29 .71 c

ATOM 37 C PHE A 6 35 .390 58 .307 6 .250 1 .00 33 .27 c

ATOM 38 O PHE A 6 36 .307 57 .720 6 .800 1 .00 31 .15 o

ATOM 39 N GLU A 7 34 .659 57 .830 5 .200 1 .00 30 .85 N

ATOM 40 CA GLU A 7 35 .032 56 .659 4 .466 1 .00 31 .46 C

ATOM 41 CB GLU A 7 33 .806 55 .962 3 .976 1 .00 29 .73 C

ATOM 42 CG GLU A 7 33 .178 55 .196 5 .135 1 .00 42 .44 C

ATOM 43 CD GLU A 7 32 .462 56 .206 6 .138 1 .00 54 .16 C

ATOM 44 OEl GLU A 7 32 .878 56 .291 7 .372 1 .00 50 .02 O

ATOM 45 OE2 GLU A 7 31 .478 56 .970 5 .671 1 .00 58 .68 O

ATOM 46 C GLU A 7 35 .969 56 .992 3 .285 1 .00 31 .62 C

ATOM 47 0 GLU A 7 35 .825 58 .054 2 .517 1 .00 32 .67 o

ATOM 48 N PHE A 8 36 .947 56 .128 3 .094 1 .00 29 .73 N

ATOM 49 CA PHE A 8 37 .857 56 .244 1 .912 1 .00 28 .32 C

ATOM 50 CB PHE A 8 38 .803 55 .036 1 .979 1 .00 29 .52 C

ATOM 51 CG PHE A 8 39 .951 55 .203 2 .970 1 .00 31 .47 C

ATOM 52 CD1 PHE A 8 41 .087 55 .965 2 .621 1 .00 27 .06 C

ATOM 53 CE1 PHE A 8 42 .161 56 .091 3 .535 1 .00 30 .35 C

ATOM 54 CZ PHE A 8 42 .035 55 .462 4 .826 1 .00 35 .52 C

ATOM 55 CE2 PHE A 8 40 .894 54 .834 5 .189 1 .00 28 .27 C

ATOM 56 CD2 PHE A 8 39 .863 54, .642 4 .228 1, .00 28 .15 c

ATOM 57 C PHE A 8 36 .981 55 .960 0 .664 1 .00 28 .53 C

ATOM 58 O PHE A 8 36 .007 55, .181 0 .746 1 .00 25 .53 o

ATOM 59 N GLN A 9 37 .330 56, .523 -0 .497 1. .00 28 .36 N

ATOM 60 CA GLN A 9 36 .816 55, .922 -1 .763 1 .00 27 .88 C

ATOM 61 CB GLN A 9 37. .558 56. .500 -2, .968 1, .00 26, .01 C

ATOM 62 CG GLN A 9 37. .378 58. .031 -2 .917 1. .00 23, .72 C

ATOM 63 CD GLN A 9 35, .906 58. .408 -3, .200 1, .00 30, ,71 c

ATOM 64 OEl GLN A 9 35. .406 58, .138 -4, .312 1 .00 28, .93 o

ATOM 65 NE2 GLN A 9 35. .198 58. ,985 -2, .172 1. .00 22. .68 N

ATOM 66 C GLN A 9 37, .016 54. .398 -1, .745 1. .00 30. .69 C

ATOM 67 O GLN A 9 38. ,033 53. ,894 -1. .194 1, .00 29. ,51 0

ATOM 68 N ALA A 10 36. ,116 53. ,650 -2, .404 1. .00 31, .01 N

ATOM 69 CA ALA A 10 36, .256 52, .175 -2, .339 1, .00 32, .67 C

ATOM 70 CB ALA A 10 34, .969 51. .383 -2, .874 1, .00 29. ,51 C

ATOM 71 C ALA A 10 37, .593 51. .591 -2, .869 1, .00 32. .41 C

ATOM 72 O ALA A 10 38. ,058 50. ,547 -2, .373 1, .00 33. ,44 0

ATOM 73 N GLU A 11 38, ,154 52. .211 -3. .883 1, .00 31, ,20 N

ATOM 74 CA GLU A 11 39. ,352 51. .640 -4. .491 1. ,00 31. ,99 C

ATOM 75 CB GLU A 11 39. ,677 52. ,373 -5. .736 1, ,00 30. ,70 C

ATOM 76 CG GLU A 11 38. ,696 51. ,931 -6. ,892 1. ,00 38. ,04 C

ATOM 77 CD GLU A 11 37. ,366 52. ,779 -6. .986 1. .00 44. ,36 C

ATOM 78 OEl GLU A 11 36. ,661 52. ,690 -8. ,040 1. ,00 47. ,19 0

ATOM 79 OE2 GLU A 11 37. .022 53. ,547 -6. ,034 1. ,00 35. .60 O

ATOM 80 C GLU A 11 40. .517 51. ,759 -3, ,487 1, ,00 33, .13 C

ATOM 81 O GLU A 11 41. ,331 50. ,895 -3. .432 1. ,00 32. ,30 0

ATOM 82 N ILE A 12 40. .572 52. .855 -2, ,706 1. .00 31. ,79 N

ATOM 83 CA ILE A 12 41. ,609 52. .992 -1. ,721 1. ,00 30. ,48 C

ATOM 84 CB ILE A 12 41. ,683 54. .381 -1. .132 1. .00 28. ,45 C

ATOM 85 CGI ILE A 12 41. ,772 55. 390 -2. ,280 1. ,00 22. ,88 C

ATOM 86 CD1 ILE A 12 41. .325 56. .774 -1. .824 1. ,00 20. ,90 C

ATOM 87 CG2 ILE A 12 42. .876 54. 423 -0. .122 1. 00 25. 58 C

ATOM 88 C ILE A 12 41. ,550 51. 925 -0. ,624 1. ,00 31. 90 C

ATOM 89 O ILE A 12 42. ,599 51. ,291 -0. .347 1. ,00 32. ,09 O

ATOM 90 N THR A 13 40. ,357 51. 668 -0. .107 1. ,00 30. 48 N

ATOM 91 CA THR A 13 40. ,128 50. ,599 0. .861 1. ,00 32. ,16 C

ATOM 92 CB THR A 13 38. ,600 50. 490 1. .074 1. 00 33. 07 C

ATOM 93 OG1 THR A 13 38. ,154 51. ,734 1. ,578 1. ,00 32. ,33 O

ATOM 94 CG2 THR A 13 38. ,239 49. 332 2. ,169 1. 00 31. 02 C

ATOM 95 C THR A 13 40. ,529 49. ,198 0. ,331 1. .00 32. .29 C

ATOM 96 O THR A 13 41. ,027 48. 349 1. ,112 1. 00 32. 10 O

ATOM 97 N GLN A 14 40. ,137 48. 908 -0. ,907 1. ,00 31. 28 N

ATOM 98 CA GLN A 14 40. ,509 47. ,689 -1. ,552 1. ,00 33. ,80 C

ATOM 99 CB GLN A 14 39. ,940 47. 596 -2. ,983 1. 00 34. 21 C

ATOM 100 CG GLN A 14 38. .430 47. ,533 -2. ,992 1. ,00 42. ,32 C

ATOM 101 CD GLN A 14 37. ,716 47. 654 -4. ,372 1. 00 49. 24 C

ATOM 102 OEl GLN A 14 38. .309 47. ,935 -5. ,454 1. 00 46. ,85 O

ATOM 103 NE2 GLN A 14 36. ,406 47. 399 -4. 314 1. 00 53. 56 N ATOM 104 C GLN A 14 42.108 47.634 -1.615 1.00 35.06 c

ATOM 105 O GLN A 14 42 .730 46 .577 -1 .295 1 .00 33 .78 0

ATOM 106 N LEU A 15 42 .749 48 .720 -2 .064 1 .00 32 .13 N

ATOM 107 CA LEU A 15 44 .148 48 .569 -2 .201 1 .00 33 .46 C

ATOM 108 CB LEU A 15 44 .784 49 .792 -2 .849 1 .00 31 .93 C

ATOM 109 CG LEU A 15 46 .328 49 .698 -2 .965 1 .00 32 .45 C

ATOM 110 CDl LEU A 15 46 .898 48 .412 -3 .787 1 .00 31 .05 c

ATOM 111 CD2 LEU A 15 46 .921 50 .964 -3 .624 1 .00 30 .12 c

ATOM 112 C LEU A 15 44 .777 48 .273 -0 .766 1 .00 33 .80 c

ATOM 113 O LEU A 15 45 .644 47 .442 -0 .645 1 .00 32 .82 0

ATOM 114 N MET A 16 44 .301 48 .958 0 .276 1 .00 31 .11 N

ATOM 115 CA MET A 16 44 .876 48 .813 1 .569 1 .00 32 .88 C

ATOM 116 CB MET A 16 44 .335 49 .822 2 .564 1 .00 30 .16 C

ATOM 117 CG MET A 16 44 .713 51 .230 2 .219 1 .00 32 .62 C

ATOM 118 SD MET A 16 44 .140 52 .356 3 .591 1 .00 33 .18 S

ATOM 119 CE MET A 16 42 .351 52 .251 3 .385 1 .00 26 .42 C

ATOM 120 C MET A 16 44 .692 47 .374 2 .071 1 .00 33 .71 C

ATOM 121 O MET A 16 45 .564 46 .845 2 .757 1 .00 32 .80 0

ATOM 122 N SER A 17 43 .581 46 .775 1 .673 1 .00 33 .54 N

ATOM 123 CA SER A 17 43 .292 45 .423 2 .011 1 .00 35 .35 C

ATOM 124 CB SER A 17 41 .882 44 .998 1 .583 1 .00 34 .56 C

ATOM 125 OG SER A 17 41 .658 43 .805 2 .307 1 .00 41 .92 O

ATOM 126 C SER A 17 44 .300 44 .449 1 .350 1 .00 35 .27 C

ATOM 127 O SER A 17 44 .736 43 .528 2 .018 1 .00 35 .21 o

ATOM 128 N LEU A 18 44 .593 44 .590 0 .064 1 .00 34 .00 N

ATOM 129 CA LEU A 18 45 .548 43 .744 -0 .536 1 .00 34 .07 C

ATOM 130 CB LEU A 18 45 .708 44 .199 -1 .957 1 .00 34 .84 c

ATOM 131 CG LEU A 18 44 .418 44 .005 -2 .747 1 .00 37 .01 c

ATOM 132 CDl LEU A 18 44 .627 44 .492 -4 .170 1 .00 27 .80 c

ATOM 133 CD2 LEU A 18 43 .857 42 .485 -2 .668 1 .00 35 .40 c

ATOM 134 C LEU A 18 46 .953 43 .931 0 .149 1 .00 35 .50 c

ATOM 135 O LEU A 18 47 .722 42, .957 0 .329 1 .00 35 .17 0

ATOM 136 N ILE A 19 47 .319 45, .190 0, .418 1, .00 34 .40 N

ATOM 137 CA ILE A 19 48 .641 45 .520 0 .875 1 .00 33 .54 C

ATOM 138 CB ILE A 19 48 .936 47, .028 0 .906 1 .00 32 .06 C

ATOM 139 CGI ILE A 19 48 .867 47, .816 -0, .483 1 .00 29 .55 C

ATOM 140 CDl ILE A 19 50, .087 47, .546 -1, .422 1, .00 46, .07 c

ATOM 141 CG2 ILE A 19 50, .251 47, .252 1. .572 1, ,00 29. .66 c

ATOM 142 C ILE A 19 48 .798 44, ,953 2, .286 1, .00 35 .25 c

ATOM 143 O ILE A 19 49, .810 44, .343 2. .603 1, .00 37, .92 0

ATOM 144 N ILE A 20 47, .856 45. .173 3, .165 1. .00 34, .98 N

ATOM 145 CA ILE A 20 48, .030 44. .752 4, .530 1. .00 33, .93 C

ATOM 146 CB ILE A 20 46, .913 45, .341 5, .516 1, .00 34 .47 C

ATOM 147 CGI ILE A 20 47, .461 45, ,223 6, .955 1. .00 32. .43 C

ATOM 148 CDl ILE A 20 46. .806 46. ,032 8. .101 1. ,00 37. .37 C

ATOM 149 CG2 ILE A 20 45. .526 44. ,625 5. ,318 1. ,00 28, .25 C

ATOM 150 C ILE A 20 48. .083 43, ,221 4, .672 1, .00 37, .16 c

ATOM 151 O ILE A 20 48, .703 42. ,740 5. ,639 1. .00 38. .74 0

ATOM 152 N ASN A 21 47, .431 42. .484 3. ,779 1. ,00 35. .90 N

ATOM 153 CA ASN A 21 47. ,421 41. ,060 3. ,816 1. .00 39. .68 C

ATOM 154 CB ASN A 21 46. .052 40. ,522 3. ,306 1. 00 38. ,56 C

ATOM 155 CG ASN A 21 44, .976 40. ,761 4. .316 1. ,00 42. .91 C

ATOM 156 OD1 ASN A 21 45, ,111 40. ,361 5. ,459 1. .00 43. ,18 O

ATOM 157 ND2 ASN A 21 43. ,995 41. ,595 3. ,959 1. ,00 43. ,77 N

ATOM 158 C ASN A 21 48. ,544 40. 371 2. ,961 1. 00 41. ,01 C

ATOM 159 O ASN A 21 48, .818 39. ,206 3. ,200 1. ,00 41, ,49 O

ATOM 160 N THR A 22 49, .123 41. ,053 1. ,952 1. ,00 39. ,79 N

ATOM 161 CA THR A 22 50, .016 40. 349 1. 047 1. 00 37. .80 C

ATOM 162 CB THR A 22 50. ,453 41. 207 -0. 048 1. 00 35. ,83 C

ATOM 163 OG1 THR A 22 51. ,302 40. 413 -0. ,864 1. 00 34. ,94 O

ATOM 164 CG2 THR A 22 51. ,343 42. ,351 0. ,448 1. 00 32. ,78 C

ATOM 165 C THR A 22 51. ,230 39. 747 1. 855 1. 00 38. ,77 C

ATOM 166 O THR A 22 51. ,690 40. 328 2. 861 1. 00 36. ,64 O

ATOM 167 N VAL A 23 51. ,629 38. 547 1. 451 1. 00 39. ,34 N

ATOM 168 CA VAL A 23 52. .802 37. ,878 2. ,039 1, 00 41. ,17 C

ATOM 169 CB VAL A 23 52. ,642 36. ,287 2. ,157 1. 00 42. ,23 C

ATOM 170 CGI VAL A 23 51. ,379 35. 827 2. 999 1. 00 39. ,69 c

ATOM 171 CG2 VAL A 23 52. ,619 35. 619 0. 757 1. 00 40. 95 c

ATOM 172 C VAL A 23 54. .032 38. ,244 1. ,168 1. 00 41. ,50 c

ATOM 173 O VAL A 23 55. .108 37. 802 1. 467 1. 00 43. 85 0

ATOM 174 N TYR A 24 53. .873 39. 037 0. 100 1. 00 40. ,29 N

ATOM 175 CA TYR A 24 54. ,998 39. 587 -0. 648 1. 00 40. 10 C

ATOM 176 CB TYR A 24 54. ,676 40. 997 -1. 179 1. 00 39. 80 C

ATOM 177 CG TYR A 24 55. ,749 41. 591 -2. 049 1. 00 34. ,05 C

ATOM 178 CDl TYR A 24 56. ,033 41. 066 -3. 344 1. 00 32. 70 C

ATOM 179 CE1 TYR A 24 57. .065 41. 651 -4. 208 1. 00 29. 72 c

ATOM 180 CZ TYR A 24 57. ,741 42. 748 -3. 697 1. 00 31. 10 c ATOM 181 OH TYR A 24 58.730 43.406 -4.407 1.00 39.96 0

ATOM 182 CE2 TYR A 24 57 .466 43 .275 -2 .420 1 .00 27 .19 c

ATOM 183 CD2 TYR A 24 56 .502 42 .630 -1 .579 1 .00 30 .67 c

ATOM 184 C TYR A 24 56 .209 39 .736 0 .297 1 .00 41 .92 c

ATOM 185 O TYR A 24 56 .144 40 .457 1 .354 1 .00 42 .34 0

ATOM 186 N SER A 25 57 .313 39 .113 -0 .061 1 .00 40 .80 N

ATOM 187 CA SER A 25 58 .354 38 .975 0 .950 1 .00 43 .86 C

ATOM 188 CB SER A 25 59 .127 37 .611 0 .838 1 .00 44 .29 C

ATOM 189 OG SER A 25 59 .700 37 .532 -0 .482 1 .00 48 .51 0

ATOM 190 C SER A 25 59 .349 40 .115 0 .915 1 .00 43 .50 C

ATOM 191 O SER A 25 60 .191 40 .115 1 .768 1 .00 48 .00 o

ATOM 192 N ASN A 26 59 .279 41 .098 0 .001 1 .00 41 .16 N

ATOM 193 CA ASN A 26 60 .283 42 .175 -0 .032 1 .00 38 .28 C

ATOM 194 CB ASN A 26 60 .727 42 .313 -1 .487 1 .00 38 .51 C

ATOM 195 CG ASN A 26 61 .728 43 .418 -1 .729 1 .00 42 .71 C

ATOM 196 OD1 ASN A 26 62 .637 43 .713 -0 .906 1 .00 45 .19 O

ATOM 197 ND2 ASN A 26 61 .595 44 .047 -2 .899 1 .00 49 .74 N

ATOM 198 C ASN A 26 59 .699 43 .450 0 .606 1 .00 38 .99 C

ATOM 199 O ASN A 26 59 .615 44 .542 -0 .003 1 .00 37 .95 O

ATOM 200 N LYS A 27 59 .257 43 .313 1 .849 1 .00 37 .46 N

ATOM 201 CA LYS A 27 58 .505 44 .392 2 .476 1 .00 37 .60 C

ATOM 202 CB LYS A 27 57 .847 43 .926 3 .766 1 .00 37 .42 C

ATOM 203 CG LYS A 27 56 .615 42 .911 3 .555 1 .00 39 .00 C

ATOM 204 CD LYS A 27 56 .246 42 .195 4 .894 1 .00 45 .46 C

ATOM 205 CE LYS A 27 54 .777 41 .699 4 .985 1 .00 44 .40 C

ATOM 206 NZ LYS A 27 54 .290 40 .943 3 .790 1 .00 49 .05 N

ATOM 207 C LYS A 27 59 .257 45 .647 2 .697 1 .00 37 .96 C

ATOM 208 O LYS A 27 58 .672 46 .708 2 .961 1 .00 38 .19 O

ATOM 209 N GLU A 28 60 .571 45 .598 2 .617 1, .00 36 .68 N

ATOM 210 CA GLU A 28 61 .307 46 .802 3 .037 1, .00 34 .72 C

ATOM 211 CB GLU A 28 62 .777 46 .413 3 .078 1, .00 35 .81 C

ATOM 212 CG GLU A 28 63 .333 45 .838 1 .749 1, .00 40, .21 C

ATOM 213 CD GLU A 28 64, .785 45, .374 1. .936 1. .00 45, .63 C

ATOM 214 OEl GLU A 28 64, .928 44, .514 2. .828 1. .00 47, .67 O

ATOM 215 OE2 GLU A 28 65, .725 45 .896 1. .270 1. .00 41. .22 O

ATOM 216 C GLU A 28 61 .184 47 .959 2 .030 1, .00 33 .73 C

ATOM 217 O GLU A 28 61 .652 49 .111 2 .305 1, .00 31 .91 0

ATOM 218 N ILE A 29 60 .636 47 .682 0 .816 1. .00 33 .15 N

ATOM 219 CA ILE A 29 60 .415 48 .812 -0 .114 1. .00 32, .91 C

ATOM 220 CB ILE A 29 60 .044 48 .349 -1. .489 1. .00 36, .22 c

ATOM 221 CGI ILE A 29 58, .840 47 .424 -1 .492 1, .00 33, .68 c

ATOM 222 CDl ILE A 29 57, .569 48 .154 -1. .532 1. .00 37, .86 c

ATOM 223 CG2 ILE A 29 61. .202 47, .609 -2, .151 1. .00 39, ,76 c

ATOM 224 C ILE A 29 59. .482 49, .923 0, .420 1. ,00 33. .96 c

ATOM 225 O ILE A 29 59. .531 51, .044 -0, .120 1. ,00 35. ,27 0

ATOM 226 N PHE A 30 58, .770 49, .683 1, .543 1. ,00 31. ,74 N

ATOM 227 CA PHE A 30 57, .865 50, .724 2. .125 1. ,00 33. ,70 C

ATOM 228 CB PHE A 30 57. .080 50, .214 3. ,391 1. 00 33. ,45 C

ATOM 229 CG PHE A 30 57. .918 50, .298 4. ,707 1. 00 35. ,98 C

ATOM 230 CDl PHE A 30 58. .867 49. .304 5. ,010 1. 00 29. 80 C

ATOM 231 CE1 PHE A 30 59. .703 49. ,395 6. ,177 1. 00 30. 27 c

ATOM 232 CZ PHE A 30 59. ,536 50. ,439 7. ,057 1. 00 32. 80 c

ATOM 233 CE2 PHE A 30 58. .601 51. ,490 6. ,736 1. 00 34. 91 c

ATOM 234 CD2 PHE A 30 57, .802 51, .384 5, ,566 1. .00 34. ,54 c

ATOM 235 C PHE A 30 58, .600 51, .939 2. ,446 1. .00 33. ,59 c

ATOM 236 O PHE A 30 58. .149 53, ,065 2. .241 1. 00 35. ,98 0

ATOM 237 N LEU A 31 59. .788 51. .738 2. ,957 1. 00 35. 02 N

ATOM 238 CA LEU A 31 60. .579 52. ,851 3. ,503 1. 00 35. 01 C

ATOM 239 CB LEU A 31 61. ,743 52. ,261 4. ,385 1. 00 36. 99 C

ATOM 240 CG LEU A 31 62. ,579 53. ,362 4. ,966 1. 00 36. 40 c

ATOM 241 CDl LEU A 31 61. ,798 54. ,134 6. 047 1. 00 33. 24 c

ATOM 242 CD2 LEU A 31 63. ,803 52. ,741 5. 545 1. 00 45. 78 c

ATOM 243 C LEU A 31 61. 116 53. ,749 2. 404 1. 00 34. 20 c

ATOM 244 O LEU A 31 61. 107 54. ,981 2. 535 1. 00 37. 91 o

ATOM 245 N ARG A 32 61. 588 53. 162 1. 317 1. 00 34. 08 N

ATOM 246 CA ARG A 32 61. 868 53. 849 0. 019 1. 00 34. 98 C

ATOM 247 CB ARG A 32 62. 071 52. ,754 -1. 085 1. 00 35. 25 c

ATOM 248 CG ARG A 32 62. 499 53. 284 -2. 464 1. 00 40. 70 c

ATOM 249 CD ARG A 32 62. 525 52. 187 -3. 582 1. 00 44. 29 c

ATOM 250 NE ARG A 32 61. 192 51. 600 -3. 875 1. 00 42. 51 N

ATOM 251 CZ ARG A 32 61. ,003 50. ,472 -4. ,611 1. 00 42. 89 C

ATOM 252 NH1 ARG A 32 62. ,050 49. ,797 -5. ,084 1. 00 42. 15 N

ATOM 253 NH2 ARG A 32 59. ,781 50. ,009 -4. 891 1. 00 40. 42 N

ATOM 254 C ARG A 32 60. ,702 54. ,719 -0. 409 1. 00 34. 63 C

ATOM 255 O ARG A 32 60. ,889 55. ,881 -0. 739 1. 00 38. 00 O

ATOM 256 N GLU A 33 59. 492 54. ,162 -0. 424 1. 00 33. 97 N

ATOM 257 CA GLU A 33 58. 277 54. 945 -0. 822 1. 00 34. 13 C ATOM 258 CB GLU A 33 57.066 54.027 -0.858 1.00 31.57 C

ATOM 259 CG GLU A 33 57.238 52.881 -1.873 1.00 35.54 C

ATOM 260 CD GLU A 33 57.613 53.322 -3.303 1.00 45.46 C

ATOM 261 OEl GLU A 33 57.211 54.480 -3.760 1.00 46.86 O

ATOM 262 OE2 GLU A 33 58.338 52.516 -3.970 .00 42.82 O

ATOM 263 C GLU A 33 57.966 56.124 .089 ,00 32.67 C

ATOM 264 O GLU A 33 57.748 57.283 .389 ,00 34.89 O

ATOM 265 N LEU A 34 58.074 55.883 .381 .00 31.01 N

ATOM 266 CA LEU A 34 57.870 56.980 .342 00 32.26 C

ATOM 267 CB LEU A 34 57.809 56.439 .773 .00 31.32 C

ATOM 268 CG LEU A 34 56.647 55.403 .872 .00 32.40 C

ATOM 269 CDl LEU A 34 56.433 55.012 5.388 00 35.96 C

ATOM 270 CD2 LEU A 34 55.320 55.965 3.339 00 25.84 C

ATOM 271 C LEU A 34 58.963 57.989 2.253 00 33.04 C

ATOM 272 O LEU A 34 58.709 59.223 2.467 1.00 34.05 O

ATOM 273 N ILE A 35 60.193 57.530 1.929 1.00 33.11 N

ATOM 274 CA ILE A 35 61.289 58.514 1.899 1.00 33.53 C

ATOM 275 CB ILE A 35 62.720 57.822 .047 1.00 37.02 C

ATOM 276 CGI ILE A 35 62.999 57.443 .527 1.00 34.01 C

ATOM 277 CDl ILE A 35 64.175 56.429 .552 1.00 39.10 C

ATOM 278 CG2 ILE A 35 63.920 58.708 .404 1.00 34.99 C

ATOM 279 C ILE A 35 61.124 59.344 .654 1.00 32.79 c

ATOM 280 O ILE A 35 61.296 60.598 .678 1.00 32.66 o

ATOM 281 N SER A 36 60.751 58.688 .444 00 31.00 N

ATOM 282 CA SER A 36 60 429 59.453 .712 .00 30.32 c

ATOM 283 CB SER A 36 60 181 58.403 .823 ,00 31.55 c

ATOM 284 OG SER A 36 59.658 59.090 .918 ,00 37.64 O

ATOM 285 C SER A 36 59.206 60.444 .599 00 30.28 c

ATOM 286 O SER A 36 59.189 61.605 .098 .00 29.14 O

ATOM 287 N ASN A 37 58.157 60.028 .912 1.00 31.19 N

ATOM 288 CA ASN A 37 57.117 61.045 .529 1.00 32.14 C

ATOM 289 CB ASN A 37 55.957 60.352 .166 1.00 31.16 C

ATOM 290 CG ASN A 37 55.119 59.492 .828 1.00 34.85 C

ATOM 291 OD1 ASN A 37 55.504 59.288 .023 1.00 39.88 O

ATOM 292 ND2 ASN A 37 54.045 58.937 .340 33.94 N

ATOM 293 C ASN A 37 57.643 62.154 .316 32.85 C

ATOM 294 O ASN A 37 57.285 63.347 .104 34.71 O

ATOM 295 N ALA A 38 58.489 61.824 .309 34.00 N

ATOM 296 CA ALA A 38 59.038 62.915 2.163 34.50 C

ATOM 297 CB ALA A 38 59.916 62.355 3.193 33.09 C

ATOM 298 C ALA A 38 59.850 63.845 1.262 35.50 c

ATOM 299 O ALA A 38 59.771 65.053 1.350 37.20 o

ATOM 300 N SER A 39 60.603 63.287 0.339 34.96 N

ATOM 301 CA SER A 39 61.399 64.136 -0.567 1.00 35.84 C

ATOM 302 CB SER A 39 62.437 63.268 -1.400 1.00 36.28 C

ATOM 303 OG SER A 39 63.073 64.140 -2.376 1.00 41.19 O

ATOM 304 C SER A 39 60.572 65.006 -1.452 1.00 34.62 c

ATOM 305 O SER A 39 60.897 66.198 -1.629 .00 34.67 o^'

ATOM 306 N ASP A 40 59.507 64.455 -2.050 ,00 35.49 N

ATOM 307 CA ASP A 40 58.548 65.333 -2.778 ,00 36.14 C

ATOM 308 CB ASP A 40 57.396 64.571 -3.435 00 36.58 C

ATOM 309 CG ASP A 40 57.846 63.451 -4.306 ,00 41.55 C

ATOM 310 OD1 ASP A 40 59.055 63.396 -4.708 00 48.45 O

ATOM 311 OD2 ASP A 40 57.049 62.539 .654 .00 50.68 O

ATOM 312 C ASP A 40 57.860 66.437 .944 1.00 36.25 C

ATOM 313 O ASP A 40 57.638 67.588 .469 1.00 35.94 O

ATOM 314 N ALA A 41 57.450 66.111 .706 1.00 35.74 N

ATOM 315 CA ALA A 41 56.825 67.154 .180 1.00 36.76 C

ATOM 316 CB ALA A 41 56.451 66.588 .524 1.00 35.13 C

ATOM 317 C ALA A 41 57.856 68.278 .388 1.00 38.63 C

ATOM 318 O ALA A 41 57.492 69.460 .473 1.00 38.04 O

ATOM 319 N LEU A 42 59.137 67.897 0.475 1.00 37.68 N

ATOM 320 CA LEU A 42 60.180 68.896 0.655 1.00 39.75 C

ATOM 321 CB LEU A 42 61.513 68.240 1.102 1.00 39.10 C

ATOM 322 CG LEU A 42 61.489 67.614 2.496 42.16 C

ATOM 323 CDl LEU A 42 62.639 66.667 2.740 41.17 c

ATOM 324 CD2 LEU A 42 61.572 68.787 3.476 44.34 c

ATOM 325 C LEU A 42 60.404 69.710 -0.627 41.06 c

ATOM 326 O LEU A 42 60.653 70.930 -0.520 41.05 0

ATOM 327 N ASP A 43 60.330 69.064 -1.816 1.00 40.73 N

ATOM 328 CA ASP A 43 60.465 69.822 -3.082 1.00 42.21 c

ATOM 329 CB ASP A 43 60.328 68.943 -4.377 1.00 39.97 c

ATOM 330 CG ASP A 43 61.416 67.999 -4.559 1.00 44.93 c

ATOM 331 OD1 ASP A 43 62.513 68.175 -3.935 1.00 45.70 0

ATOM 332 OD2 ASP A 43 61.258 66.990 -5.324 1.00 47.17 0

ATOM 333 C ASP A 43 59.336 70.851 -3.168 1.00 42.18 c

ATOM 334 O ASP A 43 59.545 71.936 -3.689 1.00 43.90 0 ATOM 335 N LYS A 44 58.115 70.457 -2.789 1.00 43.31 N

ATOM 336 CA LYS A 44 56 .962 71 .359 -2 .796 1 .00 44 .00 C

ATOM 337 CB LYS A 44 55 .693 70 .656 -2 .391 1 .00 43 .95 C

ATOM 338 CG LYS A 44 55 .160 69 .818 -3 .568 1 .00 47 .27 c

ATOM 339 CD LYS A 44 53 .954 68 .932 -3 .205 1 .00 55 .07 c

ATOM 340 CE LYS A 44 53 .590 67 .978 -4 .397 1 .00 58 .63 c

ATOM 341 NZ LYS A 44 52 .790 66 .796 -3 .983 1 .00 64 .20 N

ATOM 342 C LYS A 44 57 .205 72 .629 -2 .003 1 .00 44 .83 C

ATOM 343 O LYS A 44 57 .008 73 .710 -2 .527 1 .00 43 .42 O

ATOM 344 N ILE A 45 57 .672 72 .515 -0 .767 1 .00 46 .29 N

ATOM 345 CA ILE A 45 57 .936 73 .740 -0 .007 1 .00 48 .03 C

ATOM 346 CB ILE A 45 58 .004 73 .526 1 .542 1 .00 48 .39 C

ATOM 347 CGI ILE A 45 57 .912 74 .905 2 .235 1 .00 50 .09 C

ATOM 348 CDl ILE A 45 56 .498 75 .488 2 .229 1 .00 48 .41 C

ATOM 349 CG2 ILE A 45 59 .260 72 .760 1 .985 1 .00 41 .17 C

ATOM 350 C ILE A 45 59 .125 74 .543 -0 .523 1 .00 49 .71 C

ATOM 351 O ILE A 45 59 .068 75 .766 -0 .477 1 .00 49 .26 O

ATOM 352 N ARG A 46 60 .170 73 .872 -1 .042 1 .00 52 .84 N

ATOM 353 CA ARG A 46 61 .257 74 .564 -1 .761 1 .00 55 .25 C

ATOM 354 CB ARG A 46 62 .380 73 .647 -2 .109 1 .00 55 .02 C

ATOM 355 CG ARG A 46 63 .480 73 .848 -1 .215 1 .00 63 .82 c

ATOM 356 CD ARG A 46 64 .807 73 .798 -1 .898 1 .00 74 .40 c

ATOM 357 NE ARG A 46 64 .591 73 .029 -3 .112 1 .00 79 .26 N

ATOM 358 CZ ARG A 46 65 .234 71 .915 -3 .390 1 .00 80 .04 C

ATOM 359 NH1 ARG A 46 66 .166 71 .470 -2 .545 1 .00 75 .69 N

ATOM 360 NH2 ARG A 46 64 .933 71 .265 -4 .517 1 .00 80 .92 N

ATOM 361 C ARG A 46 60 .748 75 .229 -3 .019 1 .00 56 .33 C

ATOM 362 O ARG A 46 61 .066 76 .391 -3 .235 1 .00 57 .28 O

ATOM 363 N TYR A 47 59 .928 74 .558 -3 .823 1 .00 57 .59 N

ATOM 364 CA TYR A 47 59 .290 75 .278 -4 .926 1 .00 60 .97 C

ATOM 365 CB TYR A 47 58 .458 74 .358 -5 .873 1 .00 61 .71 C

ATOM 366 CG TYR A 47 57 .825 75 .120 -7 .074 1 .00 67 .36 C

ATOM 367 CDl TYR A 47 56 .470 75 .480 -7 .058 1 .00 73 .36 C

ATOM 368 CE1 TYR A 47 55 .879 76 .169 -8 .138 1 .00 77 .52 C

ATOM 369 CZ TYR A 47 56 .655 76 .538 -9 .241 1, .00 78 .57 C

ATOM 370 OH TYR A 47 56. .043 77 .248 -10 .266 1, .00 82 .80 O

ATOM 371 CE2 TYR A 47 58, .008 76 .224 -9 .279 1, .00 75 .09 C

ATOM 372 CD2 TYR A 47 58, .587 75 .511 -8, .191 1, .00 72 .50 C

ATOM 373 C TYR A 47 58, .516 76 .570 -4 .506 1, .00 61 .72 C

ATOM 374 O TYR A 47 58, .680 77 .629 -5 .095 1. ,00 61 .39 O

ATOM 375 N LYS A 48 57, .676 76 .484 -3 .484 1, .00 63. .39 N

ATOM 376 CA LYS A 48 56, .822 77, .603 -3 .089 1, .00 65, .06 C

ATOM 377 CB LYS A 48 55. .836 77, .191 -1, .968 1, ,00 64, .78 C

ATOM 378 CG LYS A 48 54. .442 77, .893 -2, .041 1. ,00 66, .25 C

ATOM 379 CD LYS A 48 53. .669 77, .782 -0, .747 1. ,00 65, .27 C

ATOM 380 CE LYS A 48 52. ,268 77, .296 -1, .000 1. .00 67. .34 C

ATOM 381 NZ LYS A 48 51. ,401 78, .003 -0, .051 1. .00 68. .78 N

ATOM 382 C LYS A 48 57. ,633 78. .808 -2. .646 1. .00 66. ,07 C

ATOM 383 O LYS A 48 57. ,262 79. .955 -2. .872 1. .00 66. ,62 O

ATOM 384 N SER A 49 58. ,754 78. .526 -2. .011 1. 00 67. ,39 N

ATOM 385 CA SER A 49 59. 507 79. .566 -1. ,386 1. 00 68. ,82 C

ATOM 386 CB SER A 49 60. ,233 78. ,974 -0. .203 1. 00 67. ,66 C

ATOM 387 OG SER A 49 61. ,366 78. ,257 -0. ,706 1. 00 70. ,14 O

ATOM 388 C SER A 49 60. 499 80. ,207 -2. ,380 1. 00 69. ,72 C

ATOM 389 O SER A 49 61. 266 81. ,063 -1. ,989 1. 00 70. ,04 o

ATOM 390 N LEU A 50 60, 511 79. ,772 -3. .641 1. 00 71. 13 N

ATOM 391 CA LEU A 50 61. 259 80. ,488 -4. ,679 1. 00 72. 02 C

ATOM 392 CB LEU A 50 61. 361 79. ,715 -6. ,002 1. 00 71. 76 C

ATOM 393 CG LEU A 50 62. 189 78. 434 -6. ,186 1. 00 70. 60 C

ATOM 394 CDl LEU A 50 61. 976 77. ,929 -7. ,603 1. 00 70. 60 C

ATOM 395 CD2 LEU A 50 63. 687 78. 522 -5. 867 1. 00 70. 71 C

ATOM 396 C LEU A 50 60. 593 81. 856 -4. 892 1. 00 72. 79 C

ATOM 397 O LEU A 50 61. 266 82. 867 -5. ,077 1. 00 73. 80 O

ATOM 398 N SER A 51 59. 277 81. 911 -4. 805 1. 00 73. 46 N

ATOM 399 CA SER A 51 58. 614 83. 183 -5. 032 1. 00 73. 75 C

ATOM 400 CB SER A 51 57. 493 83. 003 -6. 059 1. 00 74. 23 C

ATOM .401 OG SER A 51 56. 379 82. 348 -5. 485 1. 00 75. 40 O

ATOM 402 C SER A 51 58. 121 83. 828 -3. 719 1. 00 73. 19 C

ATOM 403 O SER A 51 57. 642 84. 947 -3. 721 1. 00 73. 78 O

ATOM 404 N ASP A 52 58. 290 83. 130 -2. 598 1. 00 71. 94 N

ATOM 405 CA ASP A 52 57. 663 83. 509 -1. 344 1. 00 69. 69 C

ATOM 406 CB ASP A 52 56. 303 82. .805 -1, ,325 1. 00 69. 07 C

ATOM 407 CG ASP A 52 55. 353 83. ,318 -0. ,286 1. 00 69. 18 C

ATOM 408 OD1 ASP A 52 55. 696 84. ,171 0. ,562 1. 00 71. 56 O

ATOM 409 OD2 ASP A 52 54. 187 82. ,866 -0. 233 1. 00 71. 59 O

ATOM 410 C ASP A 52 58. 551 82. 968 -0. 227 1. 00 68. 95 C

ATOM 411 O ASP A 52 58. 146 82. ,016 0. 447 1. 00 68. 40 O ATOM 412 N PRO A 53 59.745 83.546 -0.001 1.00 68.37 N

ATOM 413 CA PRO A 53 60 .685 82 .953 0 .968 1 .00 66 .94 C

ATOM 414 CB PRO A 53 62 .005 83 .734 0 .747 1 .00 67 .38 C

ATOM 415 CG PRO A 53 61 .619 84 .991 0 .0 8 1 .00 68 .40 C

ATOM 416 CD PRO A 53 60 .306 84 .771 -0 .625 1 .00 68 .58 C

ATOM 417 C PRO A 53 60 .213 82 .947 2 .428 1 .00 65 .75 C

ATOM 418 O PRO A 53 60 .805 82 .202 3 .212 1 .00 65 .65 O

ATOM 419 N LYS A 54 59 .172 83 .687 2 .797 1 .00 64 .58 N

ATOM 420 CA LYS A 54 58 .690 83 .597 4 .191 1 .00 64 .21 C

ATOM 421 CB LYS A 54 58 .019 84 .904 4 .660 1 .00 65 .02 C

ATOM 422 CG LYS A 54 56 .539 84 .856 5 .001 1 .00 67 .44 C

ATOM 423 CD LYS A 54 55 .800 86 .136 4 .543 1 .00 74 .97 C

ATOM 424 CE LYS A 54 54 .260 85 .861 4 .318 1 .00 79 .82 C

ATOM 425 NZ LYS A 54 53 .956 84 .716 3 .355 1 .00 79 .65 N

ATOM 426 C LYS A 54 57 .921 82 .301 4 .561 1 .00 62 .82 C

ATOM 427 O LYS A 54 57 .652 82 .007 5 .757 1 .00 62 .37 O

ATOM 428 N GLN A 55 57 .639 81 .479 3 .547 1 .00 61 .07 N

ATOM 429 CA GLN A 55 57 .022 80 .162 3 .781 1 .00 59 .19 C

ATOM 430 CB GLN A 55 56 .567 79 .532 2 .477 1 .00 59 .87 C

ATOM 431 CG GLN A 55 55 .457 80 .289 1 .786 1 .00 60 .33 C

ATOM 432 CD GLN A 55 54 .059 79 .947 2 .312 1 .00 64 .73 C

ATOM 433 OEl GLN A 55 53 .861 79 .172 3 .300 1 .00 61 .79 O

ATOM 434 NE2 GLN A 55 53 .072 80 .555 1 .670 1 .00 67 .54 N

ATOM 435 C GLN A 55 58, .000 79 .243 4 .489 1, .00 58 .40 C

ATOM 436 O GLN A 55 57 .581 78 .375 5 .278 1 .00 57 .41 O

ATOM 437 N LEU A 56 59, .312 79 .466 4 .266 1 .00 56 .18 N

ATOM 438 CA LEU A 56 60, .308 78 .662 4, .958 1, ,00 54 .25 C

ATOM 439 CB LEU A 56 61, .681 78 .764 4 .303 1, .00 53 .57 C

ATOM 440 CG LEU A 56 61. .782 78 .176 2 .893 1 .00 49 .98 C

ATOM 441 CDl LEU A 56 63, .170 78, .326 2, .409 1, .00 51, .79 C

ATOM 442 CD2 LEU A 56 61, .429 76 .730 2 .919 1, .00 43 .77 C

ATOM 443 C LEU A 56 60. .421 78, .975 6 .420 1, ,00 54, .67 C

ATOM 444 O LEU A 56 60, .861 78, .139 7, .197 1. .00 56, .22 O

ATOM 445 N GLU A 57 60. .019 80 .162 6, .833 1. .00 55, .72 N

ATOM 446 CA GLU A 57 60. .331 80, ,614 8, .222 1, .00 55, .79 C

ATOM 447 CB GLU A 57 59, ,917 82, .066 8, .463 1. ,00 56, .36 C

ATOM 448 CG GLU A 57 60. .934 83, .048 7, .901 1. .00 61, .52 C

ATOM 449 CD GLU A 57 60. ,584 84. ,502 8. ,254 1. .00 72, .53 C

ATOM 450 OEl GLU A 57 61. ,311 85. ,387 7. .723 1. ,00 74, .47 O

ATOM 451 OE2 GLU A 57 59, ,595 84. .757 9, .050 1. ,00 72, .73 O

ATOM 452 C GLU A 57 59. ,758 79. ,795 9. ,368 1. ,00 53. .85 C

ATOM 453 O GLU A 57 60. ,278 79. ,890 10. .473 1. ,00 54. .17 O

ATOM 454 N THR A 58 58. ,734 78. .985 9. .109 1. ,00 50. .65 N

ATOM 455 CA THR A 58 58. ,114 78. ,179 10. ,152 1. 00 49. .91 C

ATOM 456 CB THR A 58 56. ,741 77. ,677 9. .697 1. 00 50. ,73 C

ATOM 457 OG1 THR A 58 56. .818 77, ,424 8. .292 1. ,00 49. .67 O

ATOM 458 CG2 THR A 58 55. .674 78. ,842 9. ,821 1. 00 47. . 99 C

ATOM 459 C THR A 58 58. ,963 76. ,998 10. .523 1. 00 49. .85 C

ATOM 460 O THR A 58 58. .691 76, ,393 11. .509 1. ,00 47. .32 O

ATOM 461 N GLU A 59 59. .953 76. ,685 9. ,672 1. 00 50. ,73 N

ATOM 462 CA GLU A 59 60. ,912 75. ,624 9. ,824 1. ,00 52. ,64 C

ATOM 463 CB GLU A 59 60. ,173 74. ,300 9. .866 1. ,00 52. .68 C

ATOM 464 CG GLU A 59 61. 019 73. ,079 9. .947 1. 00 55. .86 C

ATOM 465 CD GLU A 59 61. ,728 72. ,937 11. ,298 1. 00 67. ,25 C

ATOM 466 OEl GLU A 59 62. ,846 73. ,520 11. ,438 1. 00 67. .28 O

ATOM 467 OE2 GLU A 59 61. 189 72. ,197 12. ,183 1. 00 71. .66 O

ATOM 468 C GLU A 59 61. ,980 75. ,712 8. ,625 1. 00 54. .61 C

ATOM 469 O GLU A 59 61. ,819 75. ,053 7. ,560 1. 00 53. ,99 O

ATOM 470 N PRO A 60 63. 030 76. 555 8. ,782 1. 00 55. 41 N

ATOM 471 CA PRO A 60 64. ,023 76. ,794 7. ,706 1. 00 55. ,34 C

ATOM 472 CB PRO A 60 64. 950 77. ,887 8. .313 1. 00 56. ,32 C

ATOM 473 CG PRO A 60 64. 848 77. ,653 9. 752 1. 00 55. 70 C

ATOM 474 CD PRO A 60 63. ,345 77. ,359 9. ,993 1. 00 55. ,29 C

ATOM 475 C PRO A 60 64. 839 75. ,549 7. ,409 1. 00 55. ,08 C

ATOM 476 O PRO A 60 65. ,382 75. ,390 6. 365 1. 00 53. 82 O

ATOM 477 N ASP A 61 64. ,857 74. ,614 8. ,316 1. 00 56. .59 N

ATOM 478 CA ASP A 61 65. 593 73. 396 8. ,065 1. 00 58. .93 C

ATOM 479 CB ASP A 61 65. ,853 72. 795 9. ,424 1. 00 60. ,53 C

ATOM 480 CG ASP A 61 67. ,197 72. ,207 9. ,496 1. 00 66. ,90 C

ATOM 481 OD1 ASP A 61 68. 069 72. 791 8. 763 1. 00 71. ,28 O

ATOM 482 OD2 ASP A 61 67. ,457 71. 217 10. ,254 1. 00 70. ,47 O

ATOM 483 C ASP A 61 64. 870 72. 310 7. 188 1. 00 58. 10 C

ATOM 484 O ASP A 61 63. 850 71. 777 7. 639 1. 00 56, 84 O

ATOM 485 N LEU A 62 65. 445 71. 937 6. 025 1. 00 56. 28 N

ATOM 486 CA LEU A 62 64. 880 70. 938 5. 114 1. 00 54. 26 C

ATOM 487 CB LEU A 62 65. 049 71. 387 3. 666 1. 00 54. 67 C

ATOM 488 CG LEU A 62 64. 468 72. 771 3. 281 1. 00 55. 35 C ATOM 489 CDl LEU A 62 64.994 73.171 907 1.00 58.45 C

ATOM 490 CD2 LEU A 62 62.927 72.798 201 1.00 55.00 C

ATOM 491 C LEU A 62 65.456 69.558 311 1.00 51.94 C

ATOM 492 O LEU A 62 66.589 69.311 971 1.00 54.07 O

ATOM 493 N PHE A 63 64.678 68.619 826 1.00 49.20 N

ATOM 494 CA PHE A 63 65.254 67.321 236 .00 46.29 C

ATOM 495 CB PHE A 63 65.954 67.413 610 .00 45.72 C

ATOM 496 CG PHE A 63 64.971 67.719 8.793 .00 45.63 C

ATOM 497 CDl PHE A 63 64.258 66.690 9.426 .00 43.70 C

ATOM 498 CE1 PHE A 63 63.330 66.950 10.463 .00 46.31 C

ATOM 499 CZ PHE A 63 63.148 68.279 10.886 .00 46.21 c

ATOM 500 CE2 PHE A 63 63.835 69.308 10.238 .00 45.16 c

ATOM 501 CD2 PHE A 63 64.746 69.034 9.213 .00 43.21 c

ATOM 502 C PHE A 63 64.170 66.265 6.381 .00 44.93 c

ATOM 503 O PHE A 63 62.992 66.614 6.469 .00 44.02 o

ATOM 504 N ILE A 64 64.636 65.014 6.491 .00 42.43 N

ATOM 505 CA ILE A 64 63.884 63.820 6.734 1.00 41.93 C

ATOM 506 CB ILE A 64 64.010 62.827 .521 1.00 42.53 c

ATOM 507 CGI ILE A 64 63.477 63.522 .243 1.00 43.40 c

ATOM 508 CDl ILE A 64 63.741 62.731 ,879 1.00 38.86 c

ATOM 509 CG2 ILE A 64 63.300 61.477 ,817 1.00 36.97 c

ATOM 510 C ILE A 64 64.499 63.136 .948 1.00 41.37 c

ATOM 511 O ILE A 64 65.663 63.089 8.053 1.00 40.91 o

ATOM 512 N ARG A 65 63.711 62.574 8.829 1.00 41.69 N

ATOM 513 CA ARG A 65 64.241 62.022 10.054 1.00 42.16 C

ATOM 514 CB ARG A 65 64.207 63.112 11.142 00 43.33 C

ATOM 515 CG ARG A 65 64.646 62.593 12.568 00 45.08 C

ATOM 516 CD ARG A 65 64.656 63.673 13.653 00 46.36 c

ATOM 517 NE ARG A 65 65.299 64.919 13.238 00 49.62 N

ATOM 518 CZ ARG A 65 64.845 66.127 13.567 00 51.71 C

ATOM 519 NH1 ARG A 65 63.728 66.240 14.295 00 57.87 N

ATOM 520 NH2 ARG A 65 65.484 67.218 13.183 00 43.60 N

ATOM 521 C ARG A 65 63.411 60.835 10.430 00 41.36 C

ATOM 522 O ARG A 65 62.168 60.904 10.380 00 42.17 0

ATOM 523 N ILE A 66 64.087 59.743 10.717 00 39.70 N

ATOM 524 CA ILE A 66 63.524 58.453 11.055 00 38.74 C

ATOM 525 CB ILE A 66 64.125 57.399 10.127 00 37.92 C

ATOM 526 CGI ILE A 66 63.904 57.859 8.667 00 40.10 C

ATOM 527 CDl ILE A 66 64.063 56.755 7.711 00 45.02 C

ATOM 528 CG2 ILE A 66 63.549 56.017 10.343 00 33.45 C

ATOM 529 C ILE A 66 63.872 58.190 12.518 00 42.37 C

ATOM 530 O ILE A 66 65.025 58.341 12.931 00 44.17 O

ATOM 531 N THR A 67 62.865 57.893 13.331 1.00 43.07 N

ATOM 532 CA THR A 67 63.017 57.708 14.749 1.00 42.91 C

ATOM 533 CB THR A 67 62.376 58.813 15.497 1.00 43.25 C

ATOM 534 OG1 THR A 67 62.921 60.036 15.012 1.00 44.53 O

ATOM 535 CG2 THR A 67 62.783 58.741 17.069 1.00 43.25 C

ATOM 536 C THR A 67 62.250 56.498 15.119 1.00 43.46 C

ATOM 537 O THR A 67 61.025 56.538 15.078 1.00 43.05 0

ATOM 538 N PRO A 68 62.962 55.433 15.485 1.00 43.80 N

ATOM 539 CA PRO A 68 62.311 54.239 16.058 1.00 44 70 C

ATOM 540 CB PRO A 68 63.404 53.109 15.967 1.00 43, 81 C

ATOM 541 CG PRO A 68 64.527 53.759 15.264 1.00 44.27 C

ATOM 542 CD PRO A 68 64.435 55.278 15.352 1.00 43.07 C

ATOM 543 C PRO A 68 61.938 54.527 17.501 00 44.70 C

ATOM 544 O PRO A 68 62.599 55.286 18.217 00 45.31 o

ATOM 545 N LYS A 69 60.860 53.901 17.900 00 45.38 N

ATOM 546 CA LYS A 69 60.324 54.024 19.263 00 47.09 C

ATOM 547 CB LYS A 69 59.180 55.090 19.336 00 46.78 C

ATOM 548 CG LYS A 69 59.706 56.482 19.054 00 43.43 C

ATOM 549 CD LYS A 69 58.591 57.421 19.167 00 46.47 C

ATOM 550 CE LYS A 69 58.903 58.906 18.875 00 43.29 C

ATOM 551 NZ LYS A 69 57.673 59.691 19.395 00 45.69 N

ATOM 552 C LYS A 69 59.960 52.600 19.695 00 48.55 C

ATOM 553 O LYS A 69 58.814 52.139 19.563 00 49.18 O

ATOM 554 N PRO A 70 61.007 51.861 20.074 00 50.89 N

ATOM 555 CA PRO A 70 60.914 50.400 20.234 00 51.42 C

ATOM 556 CB PRO A 70 62.346 49.988 20.662 00 50.25 C

ATOM 557 CG PRO A 70 63.284 51.146 20.285 00 49.92 C

ATOM 558 CD PRO A 70 62.382 52.387 20.383 00 52.24 C

ATOM 559 C PRO A 70 59.920 50.109 21.351 00 53.54 C

ATOM 560 O PRO A 70 59.317 49.052 21.339 00 53.20 O

ATOM 561 N GLU A 71 59.741 51.058 22.281 00 56.07 N

ATOM 562 CA GLU A 71 58.872 50.851 23.455 00 60.30 C

ATOM 563 CB GLU A 71 59.260 51.814 24.616 00 61.89 C

ATOM 564 CG GLU A 71 58.836 51.344 26.030 00 71.83 C

ATOM 565 CD GLU A 71 59.939 50.552 26.792 00 81.09 C ATOM 566 OEl GLU A 71 60.435 49.517 26.208 1.00 81.07 O

ATOM 567 OE2 GLU A 71 60 .273 50 .948 27 .981 1 .00 80 .63 0

ATOM 568 C GLU A 71 57 .366 51 .018 23 .124 1 .00 59 .72 c

ATOM 569 O GLU A 71 56 .478 50 .780 23 .987 1 .00 61 .98 o

ATOM 570 N GLN A 72 57 .081 51 .455 21 .894 1 .00 56 .96 N

ATOM 571 CA GLN A 72 55 .719 51 .678 21 .436 1 .00 53 .34 C

ATOM 572 CB GLN A 72 55 .585 53 .132 21 .150 1 .00 52 .99 c

ATOM 573 CG GLN A 72 55 .365 53 .948 22 .360 1 .00 57 .14 c

ATOM 574 CD GLN A 72 55 .636 55 .410 22 .098 1 .00 63 .29 c

ATOM 575 OEl GLN A 72 56 .643 55 .960 22 .570 1 .00 66 .06 0

ATOM 576 NE2 GLN A 72 54 .754 56 .049 21 .326 1 .00 64 .38 N

ATOM 577 C GLN A 72 55 .493 50 .827 20 .171 1 .00 50 .66 C

ATOM 578 O GLN A 72 54 .391 50 .804 19 .604 1 .00 48 .14 O

ATOM 579 N LYS A 73 56 .592 50 .149 19 .733 1 .00 47 .85 N

ATOM 580 CA LYS A 73 56 .611 49 .324 18 .484 1 .00 43 .60 C

ATOM 581 CB LYS A 73 55 .708 48 .075 18 .639 1 .00 44 .60 C

ATOM 582 CG LYS A 73 56 .165 47 .065 19 .716 1 .00 45 .58 c

ATOM 583 CD LYS A 73 55 .362 45 .709 19 .848 1 .00 54 .67 c

ATOM 584 CE LYS A 73 54 .092 45 .557 18 .954 1 .00 65 .15 c

ATOM 585 NZ LYS A 73 53 .311 44 .209 19 .118 1 .00 67 .98 N

ATOM 586 C LYS A 73 56 .231 50 .243 17 .307 1 .00 40 .49 C

ATOM 587 O LYS A 73 55 .471 49 .916 16 .437 1 .00 39 .32 O

ATOM 588 N VAL A 74 56 .741 51 .446 17 .350 1 .00 38 .99 N

ATOM 589 CA VAL A 74 56 .373 52 .506 16 .471 1 .00 40 .09 C

ATOM 590 CB VAL A 74 55 .815 53 .722 17 .276 1 .00 40 .57 C

ATOM 591 CGI VAL A 74 56 .133 55 .025 16 .611 1 .00 40 .71 C

ATOM 592 CG2 VAL A 74 54 .278 53 .571 17 .594 1 .00 40 .68 C

ATOM 593 C VAL A 74 57 .655 52 .932 15 .687 1 .00 40 .67 C

ATOM 594 O VAL A 74 58 .777 52 .952 16 .230 1. .00 39 .30 O

ATOM 595 N LEU A 75 57, .471 53 .294 14, .404 1, .00 39 .58 N

ATOM 596 CA LEU A 75 58 .566 53 .831 13 .611 1 .00 35 .25 C

ATOM 597 CB LEU A 75 58 .843 52 .879 12 .431 1 .00 33 .33 C

ATOM 598 CG LEU A 75 59, .907 53 .422 11, .423 1, .00 33, .45 c

ATOM 599 CDl LEU A 75 61, .305 53. .651 12, .160 1, .00 32, .54 c

ATOM 600 CD2 LEU A 75 60 .058 52 .413 10, .289 1. .00 33 .55 c

ATOM 601 C LEU A 75 58. .015 55 .128 13, .139 1 .00 36 .49 c

ATOM 602 O LEU A 75 56. .928 55. ,086 12, .519 1, .00 37, .41 o

ATOM 603 N GLU A 76 58. .731 56. .261 13, .308 1, .00 34, .66 N

ATOM 604 CA GLU A 76 58. . 08 57, .477 12, .804 1 .00 36, .72 C

ATOM 605 CB GLU A 76 58. .192 58, .544 13, .876 1, .00 35, .80 C

ATOM 606 CG GLU A 76 57. .241 58, .210 15. .015 1, .00 40, .48 C

ATOM 607 CD GLU A 76 57. ,069 59, ,361 15. ,991 1, ,00 43. ,20 C

ATOM 608 OEl GLU A 76 57. .881 60, .329 15, .918 1, .00 46. .20 O

ATOM 609 OE2 GLU A 76 56, ,179 59. .241 16. .850 1, .00 44, .78 0

ATOM 610 C GLU A 76 59. ,068 57. .962 11. ,671 1, .00 38, .47 C

ATOM 611 O GLU A 76 60. ,303 57. ,884 11. ,779 1. ,00 41. .27 o

ATOM 612 N ILE A 77 58. .452 58. .488 10. ,595 1, .00 37. .78 N

ATOM 613 CA ILE A 77 59, .212 59, .101 9. ,531 1, .00 36, .76 C

ATOM 614 CB ILE A 77 58. ,962 58. .406 8. ,141 1. ,00 35. ,96 C

ATOM 615 CGI ILE A 77 59. ,200 56. ,893 8. 156 1. ,00 37. ,97 C

ATOM 616 CDl ILE A 77 58, .116 56, ,164 8. ,744 1, .00 47. .67 C

ATOM 617 CG2 ILE A 77 59. ,891 59, .027 7. ,106 1, ,00 31. ,15 C

ATOM 618 C ILE A 77 58. ,795 60. ,540 9. .445 1. ,00 36. ,89 c

ATOM 619 O ILE A 77 57. ,726 60. ,814 8. ,974 1. ,00 38. ,30 0

ATOM 620 N ARG A 78 59, ,667 61. .472 9. ,736 1, ,00 36. .24 N

ATOM 621 CA ARG A 78 59, ,304 62. ,837 9. ,659 1. ,00 35. ,96 C

ATOM 622 CB ARG A 78 59, ,766 63. ,487 10. ,941 1. .00 36. ,10 C

ATOM 623 CG ARG A 78 59. ,764 64. ,900 10. 768 1. .00 40. ,35 C

ATOM 624 CD ARG A 78 59, ,316 65, .552 11. ,890 1, .00 49. ,59 C

ATOM 625 NE ARG A 78 59, ,423 67. ,012 11. ,879 1, ,00 53. ,48 N

ATOM 626 CZ ARG A 78 59. ,692 67. ,597 13. ,048 1. ,00 55. ,05 C

ATOM 627 NH1 ARG A 78 59. ,852 66. ,819 14. 130 1. ,00 54. ,37 N

ATOM 628 NH2 ARG A 78 59, ,768 68. .900 13. ,180 1, .00 58. .13 N

ATOM 629 C ARG A 78 59, ,958 63. .588 8. ,503 1. ,00 37. .22 C

ATOM 630 O ARG A 78 61. ,106 63. ,319 8. 185 1. ,00 36. ,97 O

ATOM 631 N ASP A 79 59. ,246 64. ,573 7. 907 1. ,00 37. ,55 N

ATOM 632 CA ASP A 79 59, .842 65. .535 6. ,982 1. .00 37. .63 C

ATOM 633 CB ASP A 79 59, .469 65. ,240 5. ,497 1. ,00 36. ,56 C

ATOM 634 CG ASP A 79 57, ,949 65. ,299 5. 231 1. ,00 40. ,11 C

ATOM 635 OD1 ASP A 79 57. ,388 66. ,435 5. 116 1. ,00 36. ,53 O

ATOM 636 OD2 ASP A 79 57, .243 64. ,244 5. ,245 1. .00 35. ,15 O

ATOM 637 C ASP A 79 59, .424 66, ,960 7, 334 1. ,00 38. ,14 C

ATOM 638 O ASP A 79 58. ,335 67. ,175 7. 893 1, ,00 39. ,80 O

ATOM 639 N SER A 80 60. ,242 67. ,935 6. 973 1. 00 36. 82 N

ATOM 640 CA SER A 80 59, ,817 69. .326 7. ,100 1. ,00 37. ,59 C

ATOM 641 CB SER A 80 60, .947 70. ,226 7. ,714 1. ,00 36. ,19 C

ATOM 642 OG SER A 80 62. .097 70. ,255 6. 856 1. ,00 37. ,67 O ATOM 643 C SER A 80 59.324 69.884 5.758 1.00 37.34 c

ATOM 644 O SER A 80 59 .639 71 .032 5 .389 1 .00 37 .07 0

ATOM 645 N GLY A 81 58 .494 69 .092 5 .029 1 .00 39 .45 N

ATOM 646 CA GLY A 81 57 .985 69 .514 3 .736 1 .00 35 .99 C

ATOM 647 C GLY A 81 56 .767 70 .405 3 .951 1 .00 38 .34 C

ATOM 648 O GLY A 81 56 .529 70 .985 5 .045 1 .00 37 .35 0

ATOM 649 N ILE A 82 55 .976 70 .504 2 .891 1 .00 37 .43 N

ATOM 650 CA ILE A 82 54 .951 71 .470 2 .840 1 .00 36 .54 C

ATOM 651 CB ILE A 82 54 .366 71 .606 1 .376 1 .00 37 .21 C

ATOM 652 CGI ILE A 82 53 .414 72 .787 1 .259 1 .00 40 .17 C

ATOM 653 CDl ILE A 82 S3 .306 73 .189 -0 .158 1 .00 48 .07 C

ATOM 654 CG2 ILE A 82 53 .699 70 .398 0 .934 1 .00 32 .91 C

ATOM 655 C ILE A 82 53 .882 71 .200 3 .854 1 .00 35 .66 C

ATOM 656 O ILE A 82 53 .149 72 .107 4 .181 1 .00 34 .77 0

ATOM 657 N GLY A 83 53 .729 69 .949 4 .261 1 .00 35 .10 N

ATOM 658 CA GLY A 83 52 .667 69 .578 5 .192 1 .00 35 .05 C

ATOM 659 C GLY A 83 51 .335 69 .469 4 .518 1 .00 36 .75 c

ATOM 660 O GLY A 83 51 .159 69 .859 3 .333 1 .00 37 .16 o

ATOM 661 N MET A 84 50 .358 68 .967 5 .257 1 .00 37 .00 N

ATOM 662 CA MET A 84 48 .987 68 .972 4 .763 1 .00 37 .49 C

ATOM 663 CB MET A 84 48 .530 67 .508 4 .527 1 .00 37 .57 C

ATOM 664 CG MET A 84 49 .121 66 .837 3 .222 1 .00 40 .29 C

ATOM 665 SD MET A 84 48 .701 65 .075 3 .060 1 .00 40 .07 S

ATOM 666 CE MET A 84 49 .799 64 .476 4 .263 1 .00 40 .84 C

ATOM 667 C MET A 84 47 .983 69 .712 5 .784 1 .00 36 .55 C

ATOM 668 0 MET A 84 48 .031 69 .399 6 .946 1 .00 34 .59 O

ATOM 669 N THR A 85 47 .077 70 .583 5 .282 1 .00 34 .63 N

ATOM 670 CA THR A 85 45 .938 71 .148 6 .030 1 .00 35 .43 C

ATOM 671 CB THR A 85 45 .185 72 .181 5 .163 1 .00 34 .55 C

ATOM 672 OGl THR A 85 44 .679 71 .590 3, .931 1, .00 35, .67 0

ATOM 673 CG2 THR A 85 46 .119 73 .380 4 .715 1 .00 31 .19 c

ATOM 674 C THR A 85 44 .991 70 .059 6 .285 1 .00 36 .58 c

ATOM 675 O THR A 85 45 .145 68 .958 5, .683 1 .00 36 .01 0

ATOM 676 N LYS A 86 44 .025 70 .281 7 .179 1 .00 36 .76 N

ATOM 677 CA LYS A 86 43 .000 69 .249 7 .407 1 .00 36 .77 C

ATOM 678 CB LYS A 86 41, .902 69. .794 8, .307 1, .00 39, .35 C

ATOM 679 CG LYS A 86 40, .602 68 .908 8, .384 1, .00 37, .67 C

ATOM 680 CD LYS A 86 39 .613 69 .692 9 .193 1 .00 41, .25 C

ATOM 681 CE LYS A 86 38. .612 68, .763 9, .890 1, .00 41, .46 C

ATOM 682 NZ LYS A 86 37 .524 69 .645 10, .366 1, .00 44, .18 N

ATOM 683 C LYS A 86 42. .294 68 .811 6 .107 1 .00 36 .95 C

ATOM 684 O LYS A 86 42. .007 67. .642 5. .883 1. ,00 36. ,98 O

ATOM 685 N ALA A 87 41, .960 69. .760 5. .250 1. .00 35. .51 N

ATOM 686 CA ALA A 87 41. ,290 69, .421 3, .989 1, .00 34, .30 C

ATOM 687 CB ALA A 87 40, .878 70, .772 3. ,203 1. .00 34. .85 C

ATOM 688 C ALA A 87 42, .195 68, ,612 3, .066 1, .00 32, .81 C

ATOM 689 O ALA A 87 41, .703 67. .742 2, .348 1, .00 34, .35 O

ATOM 690 N GLU A 88 43. ,486 68. ,943 3. ,007 1. ,00 30. .80 N

ATOM 691 CA GLU A 88 44, .441 68, ,080 2. ,311 1, ,00 31. ,41 C

ATOM 692 CB GLU A 88 45. ,775 68. ,729 2. ,018 1. .00 33. .41 C

ATOM 693 CG GLU A 88 45. .654 70. .082 1. ,316 1. .00 35. ,25 c

ATOM 694 CD GLU A 88 46. .968 70, .872 1. .373 1. .00 45. ,09 c

ATOM 695 OEl GLU A 88 47. .750 70, ,918 2. ,381 1. ,00 41. .23 0

ATOM 696 OE2 GLU A 88 47. ,212 71. ,527 0. 373 1. 00 55. 73 0

ATOM 697 C GLU A 88 44. ,576 66. ,731 2. 921 1. ,00 30. ,91 c

ATOM 698 O GLU A 88 44. ,587 65. ,768 2. 198 1. 00 33, ,24 0

ATOM 699 N LEU A 89 44. ,502 66. ,583 4. 227 1. .00 31. ,18 N

ATOM 700 CA LEU A 89 44, ,533 65, .189 4. ,747 1. ,00 29. ,54 C

ATOM 701 CB LEU A 89 44. ,498 65. .189 6. 257 1. 00 27. 25 C

ATOM 702 CG LEU A 89 45. 814 65. .813 6. 821 1. 00 27. 71 C

ATOM 703 CDl LEU A 89 45. ,632 66. ,106 8. 357 1. 00 26. 76 C

ATOM 704 CD2 LEU A 89 46. 983 64. 868 6. 655 1. 00 22. 39 c

ATOM 705 C LEU A 89 43. ,395 64. ,357 4. 233 1. 00 31. 22 c

ATOM 706 O LEU A 89 43. ,555 63. ,153 3. 789 1. 00 31. 49 o

ATOM 707 N ILE A 90 42. 219 64. 984 4. 254 1. 00 30. 94 N

ATOM 708 CA ILE A 90 40. 995 64. 272 3. 884 1. 00 30. 71 C

ATOM 709 CB ILE A 90 39. .737 65. 152 4. 186 1. 00 30. 80 C

ATOM 710 CGI ILE A 90 39. 653 65. 317 5. 725 1. 00 29. 85 C

ATOM 711 CDl ILE A 90 38. ,727 66. ,405 6. 251 1. 00 27. 55 C

ATOM 712 CG2 ILE A 90 38. .435 64. ,505 3. 562 1. 00 28. 60 c

ATOM 713 C ILE A 90 41. 042 63. 948 2. 428 1. 00 31. 06 c

ATOM 714 O ILE A 90 40. 778 62. 830 2. 041 1. 00 30. 28 0

ATOM 715 N ASN A 91 41. ,360 64. ,964 1. 641 1. 00 31. 39 N

ATOM 716 CA ASN A 91 41. 276 64. 835 0. 216 1. 00 33. 58 C

ATOM 717 CB ASN A 91 41. ,428 66. .220 -0. 388 1. 00 34. 53 C

ATOM 718 CG ASN A 91 40, .780 66. ,356 -1. 800 1. 00 45. 87 C

ATOM 719 OD1 ASN A 91 41. 406 66. 934 -2. 795 1. 00 51. 62 O ATOM 720 ND2 ASN A 91 39.537 65.864 -1.913 1.00 50.41 N

ATOM 721 C ASN A 91 42 .368 63 .933 -0 .362 1 .00 31 .79 C

ATOM 722 O ASN A 91 42 .091 62 .974 -1 .086 1 .00 31 .07 O

ATOM 723 N ASN A 92 43 .598 64 .248 -0 .002 1 .00 31 .45 N

ATOM 724 CA ASN A 92 44 .753 63 .613 -0 .582 1 .00 32 .52 C

ATOM 725 CB ASN A 92 46 .021 64 .398 -0 .188 1 .00 33 .27 C

ATOM 726 CG ASN A 92 46 .069 65 .771 -0 .883 1 .00 37 .43 C

ATOM 727 OD1 ASN A 92 45 .213 66 .041 -1 .782 1 .00 39 .84 O

ATOM 7₂8 ND2 ASN A 92 47 .093 66 .585 -0 .567 1 .00 30 .54 N

ATOM 729 C ASN A 92 44 .862 62 .170 -0 .134 1 .00 32 .73 C

ATOM 730 O ASN A 92 45 .115 61 .323 -0 .991 1 .00 32 .84 O

ATOM 731 N LEU A 93 44 .618 61 .871 1 .166 1 .00 28 .98 N

ATOM 732 CA LEU A 93 44 .781 60 .482 1 .620 1 .00 26 .17 C

ATOM 733 CB LEU A 93 45 .198 60 .452 3 .132 1 .00 25 .55 C

ATOM 734 CG LEU A 93 46 .476 61 .342 3 .332 1 .00 26 .12 C

ATOM 735 CDl LEU A 93 46 .865 61 .304 4 .770 1 .00 26 .36 C

ATOM 736 CD2 LEU A 93 47 .656 60 .746 2 .479 1 .00 27 .13 C

ATOM 737 C LEU A 93 43 .515 59 .739 1 .475 1 .00 28 .04 C

ATOM 738 O LEU A 93 43 .576 58 .509 1 .363 1 .00 28 .31 O

ATOM 739 N GLY A 94 42 .314 60 .409 1 .569 1 .00 26 .74 N

ATOM 740 CA GLY A 94 41 .108 59 .599 1 .634 1 .00 25 .99 C

ATOM 741 C GLY A 94 40 .327 59 .608 0 .351 1 .00 25 .54 C

ATOM 742 O GLY A 94 39 .405 58 .840 0 .119 1 .00 27 .73 o

ATOM 743 N THR A 95 40 .678 60 .475 -0 .559 1 .00 27 .42 N

ATOM 744 CA THR A 95 39 .796 60 .630 -1 .742 1 .00 28 .50 C

ATOM 745 CB THR A 95 38 .920 61 ,989 -1, .605 1 .00 30 .57 C

ATOM 746 OG1 THR A 95 38 .130 61 .907 -0 .391 1 .00 32 .69 O

ATOM 747 CG2 THR A 95 37 .882 62 .166 -2 .808 1 .00 24 .65 C

ATOM 748 C THR A 95 40 .518 60 .623 -3 .066 1 .00 29 .63 C

ATOM 749 O THR A 95 40 .188 59 ,785 -3 .862 1 .00 32 .42 O

ATOM 750 N ILE A 96 41 .452 61 .523 -3 .332 1. .00 29 .97 N

ATOM 751 CA, ILE A 96 41 .950 61 .614 -4 .708 1 .00 31 .31 C

ATOM 752 CB ILE A 96 42 .364 63 .065 -5 .196 1. .00 31 .84 C

ATOM 753 CGI ILE A 96 43, .568 63 .512 -4 .407 1 .00 36 .25 C

ATOM 754 CDl ILE A 96 44, .152 64, .941 -4, .849 1, .00 39, .15 C

ATOM 755 CG2 ILE A 96 41, .079 64, .105 -5, .230 1, .00 31, .27 C

ATOM 756 C ILE A 96 43. .055 60, .599 -5, .120 1 .00 30, .55 C

ATOM 757 O ILE A 96 43 .444 60, .598 -6, .269 1 ,00 28, .87 0

ATOM 758 N ALA A 97 43 .494 59, .751 -4, .187 1, .00 29, .94 N

ATOM 759 CA ALA A 97 44, .295 58. .600 -4, .435 1 .00 28, .47 C

ATOM 760 CB ALA A 97 44. .784 57, .933 -3. .079 1. .00 27. ,84 C

ATOM 761 C ALA A 97 43. .488 57. .635 -5. ,209 1. ,00 28. ,53 C

ATOM 762 0 ALA A 97 43. .965 56, .564 -5, .573 1 .00 32. .40 O

ATOM 763 N LYS A 98 42, .233 57, ,917 -5, ,459 1, .00 28. ,13 N

ATOM 764 CA LYS A 98 41, .340 56, .818 -5, .985 1, .00 26. ,99 C

ATOM 765 CB LYS A 98 39. .923 57. ,382 -6. ,157 1. .00 27, ,10 C

ATOM 766 CG LYS A 98 38. .941 56. ,511 -6. ,963 1. .00 28. ,70 C

ATOM 767 CD LYS A 98 37 .644 57 .219 -7. .061 1. .00 31. .89 C

ATOM 768 CE LYS A 98 36, .713 56, ,477 -7. ,979 1. .00 40. .01 C

ATOM 769 NZ LYS A 98 35, .560 56, ,146 -7. ,024 1. ,00 50. .45 N

ATOM 770 C LYS A 98 41. .843 56, ,268 -7. ,354 1, .00 26. .77 C

ATOM 771 O LYS A 98 41. ,891 55. ,100 -7. ,551 1. ,00 25. .86 O

ATOM 772 N SER A 99 42. .180 57, .127 -8, .302 1, ,00 25. ,06 N

ATOM 773 CA SER A 99 42, .572 56, .685 -9, .656 1. .00 30. .31 C

ATOM 774 CB SER A 99 42, ,521 57. ,873 -10. .664 1. ,00 29. ,36 C

ATOM 775 OG SER A 99 43, .435 58, ,743 -10. .112 1. ,00 41. ,21 O

ATOM 776 C SER A 99 43, .984 56. .103 -9. ,720 1. ,00 28. ,11 C

ATOM 777 O SER A 99 44. ,165 55. ,155 -10. 370 1. 00 28. 95 O

ATOM 778 N GLY A 100 44. .939 56, .649 -8. .989 1. ,00 25. ,89 N

ATOM 779 CA GLY A 100 46. .188 55, .939 -8, ,705 1. ,00 26. ,19 C

ATOM 780 C GLY A 100 46. ,016 54, ,574 -8. ,106 1. 00 26. ,89 C

ATOM 781 O GLY A 100 46. .681 53. .634 -8. ,596 1. 00 27. ,33 O

ATOM 782 N THR A 101 45. .106 54, .371 -7. ,129 1. 00 2 . 26 N

ATOM 783 CA THR A 101 45. .053 53, .034 -6. ,518 1. ,00 27. 19 C

ATOM 784 CB THR A 101 44, .394 52, ,992 -5. ,171 1. ,00 29. ,24 C

ATOM 785 OG1 THR A 101 43. .044 53, .420 -5. ,314 1. ,00 27. .74 O

ATOM 786 CG2 THR A 101 45. ,068 53. ,928 -4. 122 1. 00 28. 97 C

ATOM 787 C THR A 101 44. .292 52. ,078 -7. ,492 1. 00 29. 97 C

ATOM 788 O THR A 101 44. .624 50, .823 -7. .587 1. ,00 29. .20 O

ATOM 789 N LYS A 102 43. .324 52, ,646 -8. ,238 1. 00 28. 29 N

ATOM 790 CA LYS A 102 42, .672 51, ,857 -9. ,244 1. ,00 27. ,90 C

ATOM 791 CB LYS A 102 41. ,398 52. ,505 -9. ,777 1. ,00 28. ,48 C

ATOM 792 CG LYS A 102 40. ,648 51. ,716 -10. 873 1. 00 35. 75 C

ATOM 793 CD LYS A 102 39. ,681 50, ,713 -10. ,162 1. 00 53. ,49 C

ATOM 794 CE LYS A 102 39, ,771 49. ,190 -10. ,506 1. ,00 56. .84 C

ATOM 795 NZ LYS A 102 39, .079 48. ,883 -11. 821 1. 00 54. 35 N

ATOM 796 C LYS A 102 43, .648 51, ,425 -10. 337 1. 00 27. 50 C ATOM 797 O LYS A 102 43.624 50.275 -10.771 1.00 29.17 0

ATOM 798 N ALA A 103 44 .504 52 .311 -10 .803 1 .00 27 .04 N

ATOM 799 CA ALA A 103 45 .358 51 .953 -11 .896 1 .00 27 .09 C

ATOM 800 CB ALA A 103 46 .091 53 .185 -12 .440 1 .00 26 .78 C

ATOM 801 C ALA A 103 46 .370 50 .910 -11 .377 1 .00 28 .54 C

ATOM 802 O ALA A 103 46 .788 49 .991 -12 .103 1 .00 28 .93 O

ATOM 803 N PHE A 104 46 .789 51 .078 -10 .132 1 .00 30 .05 N

ATOM 804 CA PHE A 104 47 .781 50 .143 -9 .575 1 .00 31 .08 C

ATOM 805 CB PHE A 104 48 .265 50 .643 -8 .214 1 .00 28 .59 C

ATOM 806 CG PHE A 104 49 .292 49 .719 -7 .637 1 .00 32 .79 C

ATOM 807 CDl PHE A 104 50 .427 49 .331 -8 .448 1 .00 32 .86 C

ATOM 808 CE1 PHE A 104 51 .345 48 .393 -8 .004 1 .00 34 .08 C

ATOM 809 CZ PHE A 104 51 .270 47 .894 -6 .660 1 .00 30 .38 C

ATOM 810 CE2 PHE A 104 50 .181 48 .245 -5 .856 1 .00 33 .04 C

ATOM 811 CD2 PHE A 104 49 .184 49 .206 -6 .354 1 .00 30 .08 C

ATOM 812 C PHE A 104 47 .153 48 .701 -9 .453 1 .00 31 .92 C

ATOM 813 O PHE A 104 47 .753 47 .722 -9 .847 1 .00 32 .21 O

ATOM 814 N MET A 105 45 .912 48 .594 -8 .945 1 .00 32 .17 N

ATOM 815 CA MET A 105 45 .216 47 .277 -8 .868 1 .00 32 .84 C

ATOM 816 CB MET A 105 43 .891 47 .352 -8 .113 1 .00 28 .94 C

ATOM 817 CG MET A 105 44 .172 47 .789 -6 .702 1 .00 30 .71 C

ATOM 818 SD MET A 105 42 .624 47 .656 -5 .716 1 .00 36 .16 S

ATOM 819 CE MET A 105 41 .458 49 .162 -6 .461 1 .00 26 .36 C

ATOM 820 C MET A 105 45 .025 46 .670 -10 .248 1 .00 34 .45 C

ATOM 821 O MET A 105 45 .113 45 .395 -10 .412 1 .00 35 .42 O

ATOM 822 N GLU A 106 44 .830 47 .576 -11 .247 1 .00 33 .89 N

ATOM 823 CA GLU A 106 44 .762 47 .121 -12 .614 1, .00 32 .23 C

ATOM 824 CB GLU A 106 44 .135 48 .177 -13 .538 1, .00 32 .95 C

ATOM 825 CG GLU A 106 42 .633 48 .434 -13 .186 1 .00 30 .81 C

ATOM 826 CD GLU A 106 42 .032 49 .591 -13 .970 1, .00 36 .39 C

ATOM 827 OEl GLU A 106 42 .797 50, .185 -14 .771 1, .00 38 .61 O

ATOM 828 OE2 GLU A 106 40 .784 49 .873 -13 .816 1, .00 39 .20 O

ATOM 829 C GLU A 106 46 .154 46, .597 -13 .079 1, .00 32 .87 C

ATOM 830 O GLU A 106 46 .213 45, .470 -13 .637 1, .00 35 .24 O

ATOM 831 N ALA A 107 47, .221 47. .305 -12 .732 1. ,00 29, .66 N

ATOM 832 CA ALA A 107 48 .546 46 .856 -13 .042 1, .00 32 .54 C

ATOM 833 CB ALA A 107 49, .658 47. .893 -12 .707 1, .00 33, .10 C

ATOM 834 C ALA A 107 48. .776 45, .506 -12 .335 1. .00 33, .13 C

ATOM 835 O ALA A 107 49, .255 44, .567 -12 .963 1. .00 34, .40 O

ATOM 836 N LEU A 108 48 .302 45, .355 -11 .132 1, .00 33. .31 N

ATOM 837 CA LEU A 108 48, .571 44, .099 -10 .434 1. ,00 34, .82 C

ATOM 838 CB LEU A 108 48, .240 44. .160 -8, .909 1. ,00 32, .06 C

ATOM 839 CG LEU A 108 48 .966 45, .073 -7 .927 1. .00 33, .56 C

ATOM 840 CDl LEU A 108 48, .108 45, .168 -6 .591 1. ,00 29, .88 C

ATOM 841 CD2 LEU A 108 50, .395 44. .558 -7, .549 1. ,00 32. .32 C

ATOM 842 C LEU A 108 47. ,886 42. ,927 -11, .135 1. ,00 37. ,25 C

ATOM 843 O LEU A 108 48, .438 41, .809 -11 .110 1. ,00 42, .29 O

ATOM 844 N SER A 109 46, .749 43. ,121 -11, .814 1. ,00 37. ,84 N

ATOM 845 CA SER A 109 46, .135 41. ,955 -12, .508 1. 00 37. ,96 C

ATOM 846 CB SER A 109 44, .581 42. .117 -12, .591 1. .00 36, ,68 C

ATOM 847 OG SER A 109 44, .255 43. ,146 -13, .529 1. ,00 42. ,91 O

ATOM 848 C SER A 109 46, ,744 41. ,750 -13, .908 1. 00 37. ,53 C

ATOM 849 O SER A 109 46. ,402 40. 846 -14. .597 1. 00 39. 62 O

ATOM 850 N ALA A 110 47, .642 42. ,615 -14. .333 1. ,00 36. .67 N

ATOM 851 CA ALA A 110 48, .129 42. ,590 -15. .672 1. 00 35. ,22 C

ATOM 852 CB ALA A 110 47, ,893 43. ,938 -16, .294 1. 00 33. ,76 C

ATOM 853 C ALA A 110 49, ,655 42. ,277 -15, .669 1. ,00 34. ,58 c

ATOM 854 O ALA A 110 50. ,347 42. ,520 -16, .668 1. 00 34. ,31 0

ATOM 855 N GLY A 111 50. .165 41. ,823 -14, .530 1. 00 34. ,56 N

ATOM 856 CA GLY A 111 51. ,565 41. ,443 -14. ,374 1. 00 35. 72 C

ATOM 857 C GLY A 111 52, ,475 42. ,283 -13, ,448 1. 00 37. ,71 C

ATOM 858 O GLY A 111 53, .655 41. .904 -13. ,338 1. 00 40. 82 O

ATOM 859 N ALA A 112 52. ,059 43. 449 -12. ,893 1. 00 34. 73 N

ATOM 860 CA ALA A 112 52, .946 44. ,218 -11, ,984 1. 00 33. ,57 C

ATOM 861 CB ALA A 112 52, .340 45. ,562 -11, ,714 1. 00 33. ,04 C

ATOM 862 C ALA A 112 53. ,049 43. ,484 -10. .627 1. 00 33. 31 C

ATOM 863 O ALA A 112 52. ,175 42. 630 -10. ,323 1. 00 34. 01 O

ATOM 864 N ASP A 113 53. .973 43. ,874 -9, .777 1. 00 31. ,73 N

ATOM 865 CA ASP A 113 53. .989 43. ,318 -8. ,420 1. 00 35. 32 C

ATOM 866 CB ASP A 113 55. ,314 42. 493 -8. ,218 1. 00 32. 90 C

ATOM 867 CG ASP A 113 56. .492 43. .363 -8, .306 1. 00 38. ,50 C

ATOM 868 OD1 ASP A 113 56. .818 43. .746 -9. ,474 1. 00 49. 59 O

ATOM 869 OD2 ASP A 113 57, ,094 43. 911 -7. ,337 1. 00 40. 06 O

ATOM 870 C ASP A 113 53. ,935 44. 505 -7. ,422 1. 00 34. 84 C

ATOM 871 O ASP A 113 54. .089 45. .645 -7. .801 1. 00 34. 68 O

ATOM 872 N VAL A 114 53. ,844 44. 200 -6. ,130 1. 00 35. 53 N

ATOM 873 CA VAL A 114 53. ,840 45. 182 -5. ,067 1. 00 33. 81 C ATOM 874 CB VAL A 114 53.952 44.448 -3.666 1.00 36.09 c

ATOM 875 CGI VAL A 114 54 .029 45 .431 -2 .462 1 .00 32 .20 c

ATOM 876 CG2 VAL A 114 52 .822 43 .507 -3 .483 1 .00 31 .52 c

ATOM 877 C VAL A 114 54 .898 46 .275 -5 .179 1 .00 34 .45 c

ATOM 878 O VAL A 114 54 .626 47 .452 -4 .831 1 .00 32 .98 0

ATOM 879 N SER A 115 56 .115 45 .977 -5 .630 1 .00 33 .57 N

ATOM 880 CA SER A 115 57 .214 47 .032 -5 .522 1 .00 31 .72 C

ATOM 881 CB SER A 115 58 .621 46 .414 -5 .813 1 .00 33 .66 C

ATOM 882 OG SER A 115 58 .582 45 .622 -7 .065 1 .00 36 .40 O

ATOM 883 C SER A 115 57 .021 48 .043 -6 .584 1 .00 30 .52 C

ATOM 884 O SER A 115 57 .766 48 .998 -6 .755 1 .00 31 .03 0

ATOM 885 N MET A 116 56 .044 47 .827 -7 .400 1 .00 30 .46 N

ATOM 886 CA MET A 116 55 .793 48 .878 -8 .414 1 .00 32 .59 C

ATOM 887 CB MET A 116 55 .309 48 .148 -9 .677 1 .00 33 .00 C

ATOM 888 CG MET A 116 56 .662 47 .494 -10 .483 1 .00 31 .66 C

ATOM 889 SD MET A 116 55 .900 46 .349 -11 .694 1 .00 45 .62 s

ATOM 890 CE MET A 116 55 .533 47 .684 -13 .083 1 .00 31 .66 c

ATOM 891 C MET A 116 54 .810 50 .003 -7 .988 1 .00 31 .85 c

ATOM 892 O MET A 116 54 .663 51 .062 -8 .678 1 .00 31 .88 0

ATOM 893 N ILE A 117 54 .170 49 .798 -6 .846 1 .00 29 .94 N

ATOM 894 CA ILE A 117 53 .280 50 .832 -6 .217 1 .00 32 .19 C

ATOM 895 CB ILE A 117 52 .934 50 .471 -4 .720 1 .00 31 .27 C

ATOM 896 CGI ILE A 117 51 .774 51 .313 -4 .165 1 .00 32 .07 C

ATOM 897 CDl ILE A 117 51 .230 50 .632 -2 .858 1 .00 30 .06 C

ATOM 898 CG2 ILE A 117 54 .174 50 .668 -3 .794 1 .00 31 .26 C

ATOM 899 C ILE A 117 53 .754 52 .298 -6 .345 1 .00 31 .83 c

ATOM 900 O ILE A 117 52 .954 53 .157 -6 .683 1 .00 34 .31 0

ATOM 901 N GLY A 118 55 .029 52 .604 -6 .148 1 .00 31 .41 N

ATOM 902 CA GLY A 118 55 .475 54 .007 -6 .251 1 .00 29 .94 c

ATOM 903 C GLY A 118 55, .413 54 .567 -7 .662 1 .00 31 .30 c

ATOM 904 O GLY A 118 55, .363 55 .793 -7 .871 1, .00 33, .75 0

ATOM 905 N GLN A 119 55, .277 53 .708 -8 .667 1 .00 30 .82 N

ATOM 906 CA GLN A 119 55, .086 54, .212 -10, .041 1, .00 29 .15 C

ATOM 907 CB GLN A 119 55, .378 53 .107 -11 .058 1 .00 29 .52 C

ATOM 908 CG GLN A 119 56, .823 52, .346 -10, .852 1, .00 28 .02 C

ATOM 909 CD GLN A 119 57, .951 53, .255 -11, .007 1. .00 31, .03 C

ATOM 910 OEl GLN A 119 57, .947 54 .134 -11 .882 1, .00 33 .66 0

ATOM 911 NE2 GLN A 119 58. .894 53, .155 -10, .123 1. .00 34, .34 N

ATOM 912 C GLN A 119 53, .690 54, .801 -10, .284 1. .00 28 .73 C

ATOM 913 O GLN A 119 53. ,485 55, .486 -11, .263 1, .00 29, .55 O

ATOM 914 N PHE A 120 52, .715 54, .483 -9, .416 1, .00 28, .90 N

ATOM 915 CA PHE A 120 51, ,352 54, .920 -9, .543 1. ,00 27, .28 C

ATOM 916 CB PHE A 120 50. ,457 53. .745 -9. .330 1. ,00 25, .85 C

ATOM 917 CG PHE A 120 50. ,586 52. .722 -10, .481 1. .00 32, .09 C

ATOM 918 CDl PHE A 120 51. .634 51. ,759 -10. .487 1. .00 31. ,44 C

ATOM 919 CE1 PHE A 120 51, .788 50. .894 -11. .506 1. ,00 34, .55 C

ATOM 920 CZ PHE A 120 50. ,834 50. .946 -12, .631 1. ,00 35, .65 C

ATOM 921 CE2 PHE A 120 49. 832 51. .861 -12. .599 1. 00 33, ,57 C

ATOM 922 CD2 PHE A 120 49. ,698 52. ,748 -11. .558 1. ,00 27, .31 C

ATOM 923 C PHE A 120 50. ,988 56. ,037 -8. ,631 1. 00 27. ,83 C

ATOM 924 O PHE A 120 49. ,863 56. ,390 -8. .543 1. ,00 28, .16 O

ATOM 925 N GLY A 121 51. ,918 56. ,589 -7. ,876 1. 00 30. ,13 N

ATOM 926 CA GLY A 121 51. ,592 57. .784 -7. ,143 1. ,00 27, .61 C

ATOM 927 C GLY A 121 50. ,963 57. ,429 -5. .820 1. 00 28. .44 C

ATOM 928 O GLY A 121 50. 595 58. ,357 -5. 117 1. 00 27. ,66 O

ATOM 929 N VAL A 122 50. ,868 56. ,119 -5. ,472 1. 00 28. ,45 N

ATOM 930 CA VAL A 122 50. 265 55. ,733 -4. 235 1. 00 26. ,88 C

ATOM 931 CB VAL A 122 48. .953 54. ,941 -4. .534 1. 00 27. ,53 C

ATOM 932 CGI VAL A 122 47. 920 55. ,914 -5. ,245 1. 00 27. ,75 C

ATOM 933 CG2 VAL A 122 49. 205 53. 687 -5. 399 1. 00 21. 46 C

ATOM 934 C VAL A 122 51. 138 54. ,959 -3. ,229 1. 00 28. ,47 C

ATOM 935 O VAL A 122 50. 597 54. 148 -2 . 467 1. 00 24. 98 O

ATOM 936 N GLY A 123 52. ,478 55. ,088 -3. ,354 1. 00 29. ,37 N

ATOM 937 CA GLY A 123 53. 422 54. 455 -2. 478 1. 00 30. 16 C

ATOM 938 C GLY A 123 53. ,129 54. ,660 -0. ,979 1. 00 31. ,99 C

ATOM 939 O GLY A 123 53. 425 53. 757 -0. 163 1. 00 31. ,08 O

ATOM 940 N PHE A 124 52. 580 55. 834 -0. 584 1. 00 32. 13 N

ATOM 941 CA PHE A 124 52. ,130 56. 028 0. 832 1. 00 29. ,46 C

ATOM 942 CB PHE A 124 51. 091 57. 174 0. 862 1. 00 29. 13 C

ATOM 943 CG PHE A 124 50, ,369 57. 307 2. ,212 1. 00 32. ,05 c

ATOM 944 CDl PHE A 124 50. 986 58. 010 3. 296 1. 00 30. 26 c

ATOM 945 CE1 PHE A 124 50. 339 58. 090 4. 603 1. 00 34. 45 c

ATOM 946 CZ PHE A 124 49. 132 57. 482 4. 804 1. 00 29. ,94 c

ATOM 947 CE2 PHE A 124 48. 445 56. 817 3. 684 1. 00 32. 45 c

ATOM 948 CD2 PHE A 124 49. ,092 56. ,683 2. 423 1. 00 30. ,77 c

ATOM 949 C PHE A 124 51. 537 54. 705 1. 394 1. 00 29. 12 c

ATOM 950 O PHE A 124 51. ,899 54. ,290 2. 467 1. 00 29. ,11 0 005 0

ATOM 951 N TYR A 125 50 .596 54 .062 0 .673 1 .00 28 .34 N

ATOM 952 CA TYR A 125 49 .860 52 .933 1 .212 1 .00 29 .17 C

ATOM 953 CB TYR A 125 48 .596 52 .602 0 .320 1 .00 28 .35 C

ATOM 954 CG TYR A 125 47 .701 53 .819 0 .182 1 .00 29 .46 C

ATOM 955 CDl TYR A 125 46 .716 54 .160 1 .237 1 .00 28 .19 C

ATOM 956 CE1 TYR A 125 45 .996 55 .333 1 .213 1 .00 24 .53 C

ATOM 957 CZ TYR A 125 46 .143 56 .178 0 .089 1 .00 26 .23 c

ATOM 958 OH TYR A 125 45 .462 57 .338 0 .032 1 .00 27 .29 0

ATOM 959 CE2 TYR A 125 47 .056 55, .888 -0 .955 1 .00 29 .39 c

ATOM 960 CD2 TYR A 125 47 .869 54 .701 -0 .854 1 .00 29 .73 c

ATOM 961 C TYR A 125 50 .716 51 .702 1 .422 1 .00 32 .25 c

ATOM 962 O TYR A 125 50 .283 50 .730 2 .139 1 .00 34 .45 0

ATOM 963 N SER A 126 51 .925 51 .702 0 .832 1 .00 31 .00 N

ATOM 964 CA SER A 126 52 .855 50 .584 1 .018 1 .00 32 .24 C

ATOM 965 CB SER A 126 54 .128 SO .715 0 .091 1 .00 29 .59 C

ATOM 966 OG SER A 126 55 .023 51. .677 0 .725 1, .00 33 .63 0

ATOM 967 C SER A 126 53 .229 50 .414 2 .576 1 .00 30 .72 C

ATOM 968 O SER A 126 53 .565 49 .276 3 .036 1 .00 29 .36 0

ATOM 969 N LEU A 127 53 .049 51. .462 3. .373 1. .00 30 .39 N

ATOM 970 CA LEU A 127 53 .340 51. .385 4, .795 1 .00 30 .24 C

ATOM 971 CB LEU A 127 53 .037 52 .714 5 .464 1 .00 30 .59 C

ATOM 972 CG LEU A 127 51 .531 53 .152 5 .614 1 .00 32 .06 C

ATOM 973 CDl LEU A 127 50 .971 52. .552 6, .914 1, .00 29 .75 C

ATOM 974 CD2 LEU A 127 51 .463 54. .668 5 .616 1 .00 26 .25 C

ATOM 975 C LEU A 127 52 .556 50 .210 5 .440 1 .00 32 .04 C

ATOM 976 O LEU A 127 52 .973 49, .668 6, .479 1, ,00 29 .94 0

ATOM 911 N PHE A 128 51 .460 49, .751 4 .792 1 .00 32 .00 N

ATOM 978 CA PHE A 128 50 .713 48 .663 5 .403 1 .00 32 .05 C

ATOM 979 CB PHE A 128 49 .242 48, .602 4. .886 1. .00 33 .19 C

ATOM 980 CG PHE A 128 48 .396 49, .747 5 .427 1, .00 36 .30 C

ATOM 981 CDl PHE A 128 48 .099 49, .799 6 .817 1, .00 42 .38 C

ATOM 982 CE1 PHE A 128 47 .418 50, .865 7 .378 1, .00 41 .23 C

ATOM 983 CZ PHE A 128 47 .017 51, .976 6, ,565 1, .00 35, .97 C

ATOM 984 CE2 PHE A 128 47 .339 51. .959 5 .200 1, .00 38, .14 C

ATOM 985 CD2 PHE A 128 48 .076 50. .841 .637 1, .00 31, .95 c

ATOM 986 C PHE A 128 51 .380 47. .347 5, .212 1. .00 31, .92 c

ATOM 987 O PHE A 128 50 .841 46, .325 5, .671 1, .00 30, .29 0

ATOM 988 N LEU A 129 52 .503 47, .311 4, .479 1, .00 30, .57 N

ATOM 989 CA LEU A 129 53 .178 46. .036 4. ,371 1. .00 32. .37 C

ATOM 990 CB LEU A 129 54 .276 46. .100 3, .320 1. .00 32, .00 C

ATOM 991 CG LEU A 129 S3 .901 46, .236 1, .859 1, .00 32. .92 C

ATOM 992 CDl LEU A 129 55 .178 46, .772 1 .103 1, .00 31, .28 C

ATOM 993 CD2 LEU A 129 53 .372 44. ,918 1, .220 1. .00 28. .73 C

ATOM 994 C LEU A 129 53 .795 45, ,660 5, .751 1. .00 32. .89 C

ATOM 995 O LEU A 129 53 .945 44, .478 6, .077 1, .00 34. .20 0

ATOM 996 N VAL A 130 54 .149 46. .673 6. .534 1. ,00 32. .10 N

ATOM 997 CA VAL A 130 54 .824 46. ,478 7, .802 1. ,00 33. .67 C

ATOM 998 CB VAL A 130 56 .286 47, .075 7, .784 1, .00 32, .47 C

ATOM 999 CGI VAL A 130 57, .064 46. ,498 6. ,580 1. ,00 31, ,39 C

ATOM 1000 CG2 VAL A 130 56 .242 48. ,558 7. .782 1. .00 31. .05 C

ATOM 1001 C VAL A 130 54 .075 47. .057 9, .049 1. ,00 35. .56 C

ATOM 1002 O VAL A 130 54 .477 46, .766 10, .209 1, .00 34, .54 0

ATOM 1003 N ALA A 131 53 .001 4₇. ,825 8. .824 1. .00 34. ,0 N

ATOM 1004 CA ALA A 131 52 .255 48. .409 9, .944 1. ,00 33. .61 C

ATOM 1005 CB ALA A 131 52 .401 49, .942 9, .942 1, .00 32, .40 C

ATOM 1006 C ALA A 131 50 .775 48. ,008 9. ,861 1. .00 36. ,98 C

ATOM 1007 O ALA A 131 50 .205 47. ,689 8, .765 1. ,00 32. ,13 0

ATOM 1008 N ASP A 132 50 .146 47, .896 11, .046 1. ,00 39. ,88 N

ATOM 1009 CA ASP A 132 48, .707 47. ,801 10. ,951 1. ,00 41. ,05 C

ATOM 1010 CB ASP A 132 48 .119 46. ,612 11, ,659 1. ,00 44. ,54 C

ATOM 1011 CG ASP A 132 48 .647 46. ,422 12, .963 1. ,00 52. ,62 C

ATOM 1012 OD1 ASP A 132 48 .922 47, ,492 13, .622 1. ,00 59. ,79 0

ATOM 1013 OD2 ASP A 132 48, .896 45. ,231 13. ,358 1. ,00 58. ,72 0

ATOM 1014 C ASP A 132 47 .975 49. ,092 11. .188 1. ,00 39. ,81 C

ATOM 1015 O ASP A 132 46 .795 49, .129 11, .101 1. ,00 39. ,46 0

ATOM 1016 N ARG A 133 48, .687 50. ,197 11. ,429 1. ,00 38. 63 N

ATOM 1017 CA ARG A 133 47 .954 51. ,391 11. ,706 1. ,00 35. ,98 C

ATOM 1018 CB ARG A 133 47 .377 51. .349 13, ,148 1. ,00 34. ,43 c

ATOM 1019 CG ARG A 133 46 .717 52, ,666 13, ,620 1, ,00 42. ,19 c

ATOM 1020 CD ARG A 133 45 .906 52. .527 14, ,906 1. ,00 54. ,22 c

ATOM 1021 NE ARG A 133 46 .723 52, .262 16, ,102 1. ,00 61. ,01 N

ATOM 1022 CZ ARG A 133 46 .882 53, .125 17, ,121 1. ,00 64, ,33 C

ATOM 1023 NH1 ARG A 133 46 .255 54, .308 17, ,088 1. 00 67. 04 N

ATOM 1024 NH2 ARG A 133 47 .641 52, .801 18. ,190 1. ,00 65. ,15 N

ATOM 1025 C ARG A 133 48 .947 52, .478 11, ,460 1. ,00 35. ,21 C

ATOM 1026 O ARG A 133 50 .106 52. .26 11, ,738 1. 00 36. ,34 0

ATOM 1027 N VAL A 134 48 .510 53, .629 10, .951 1. ,00 33. ,29 N ATOM 1028 CA VAL A 134 49.366 54.766 10.898 1.00 32.09 c

ATOM 1029 CB VAL A 134 49 .762 55 .093 9 .413 1 .00 31 .14 c

ATOM 1030 CGI VAL A 134 48 .541 55 .326 8 .517 1 .00 32 .92 c

ATOM 1031 CG2 VAL A 134 50 .626 56 .346 9 .339 1 .00 30 .40 c

ATOM 1032 C VAL A 134 48 .645 55 .986 11 .564 1 .00 34 .17 c

ATOM 1033 O VAL A 134 47 .425 56 .141 11 .415 1 .00 35 .28 0

ATOM 1034 N GLN A 135 49 .386 56 .864 12 .246 1 .00 34 .16 N

ATOM 1035 CA GLN A 135 48 .954 58 .245 12 .344 1 .00 35 .61 C

ATOM 1036 CB GLN A 135 48 .940 58 .725 13 .803 1 .00 36 .80 C

ATOM 1037 CG GLN A 135 47 .914 57 .925 14 .651 1 .00 37 .52 C

ATOM 1038 CD GLN A 135 48 .159 58 .062 16 .188 1 .00 42 .13 C

ATOM 1039 OEl GLN A 135 49 .089 58 .696 16 .617 1 .00 39 .50 o

ATOM 1040 NE2 GLN A 135 47 .311 57 .437 16 .969 1 .00 41 .22 N

ATOM 1041 C GLN A 135 49 .780 59 .169 11 .527 1 .00 36 .14 C

ATOM 1042 O GLN A 135 51 .027 59 .135 11 .646 1 .00 36 .49 O

ATOM 1043 N VAL A 136 49 .097 60 .036 10 .739 1 .00 34 .02 N

ATOM 1044 CA VAL A 136 49 .764 60 .987 9 .933 1 .00 32 .05 C

ATOM 1045 CB VAL A 136 49 .216 61 .107 8 .511 1 .00 32 .88 C

ATOM 1046 CGI VAL A 136 49 .886 62 .380 7 .742 1 .00 27 .78 C

ATOM 1047 CG2 VAL A 136 49 .325 59 .787 7 .746 1 .00 31 .12 C

ATOM 1048 C VAL A 136 49 .495 62 .310 10 .697 1 .00 33 .89 C

ATOM 1049 O VAL A 136 48 .338 62 .790 10 .728 1 .00 36 .28 O

ATOM 1050 N ILE A 137 50 .558 62 .893 11 .283 1 .00 32 .44 N

ATOM 1051 CA ILE A 137 50 .513 64 .128 11 .984 1 .00 32 .45 C

ATOM 1052 CB ILE A 137 51 .358 64 .027 13 .355 1 .00 34 .66 C

ATOM 1053 CGI ILE A 137 50 .889 62 .863 14 .257 1 .00 35 .07 C

ATOM 1054 CDl ILE A 137 51 .999 61 .897 14 .757 1 .00 39 .97 C

ATOM 1055 CG2 ILE A 137 51 .296 65 .405 14 .196 1 .00 32 .77 C

ATOM 1056 C ILE A 137 51 .058 65 .159 11 .089 1 .00 32 .23 C

ATOM 1057 O ILE A 137 52 .191 65 .025 10 .607 1 .00 35 .74 O

ATOM 1058 N SER A 138 50, .351 66 .232 10 .875 1 .00 30. .94 N

ATOM 1059 CA SER A 138 50, .801 67, .157 9, .875 1, .00 33. .03 C

ATOM 1060 CB SER A 138 50 .030 66 .808 8 .523 1 .00 33 .68 C

ATOM 1061 OG SER A 138 50 .683 67 .499 7 .473 1 .00 36. .54 O

ATOM 1062 C SER A 138 50, .549 68 .584 10 .192 1 .00 33. .04 C

ATOM 1063 O SER A 138 49, .506 68 .925 10, .800 1. .00 34. .59 O

ATOM 1064 N LYS A 139 51, .433 69, .475 9, .725 1 .00 36, .42 N

ATOM 1065 CA LYS A 139 51. .316 70, .924 9, .979 1, .00 35. ,23 C

ATOM 1066 CB LYS A 139 52. .252 71, .437 11, .ISO 1. .00 35. ,49 C

ATOM 1067 CG LYS A 139 52. .241 73. .077 11. .387 1, ,00 35. .93 c

ATOM 1068 CD LYS A 139 50. .873 73, .550 11, .947 1 .00 37, .79 c

ATOM 1069 CE LYS A 139 50, .905 75, .024 12, .291 1. .00 35. .15 c

ATOM 1070 NZ LYS A 139 50. .884 75, .886 11, .080 1, .00 33. .60 N

ATOM 1071 C LYS A 139 51. .626 71, .639 8. .743 1, .00 36. ,53 C

ATOM 1072 O LYS A 139 52. ,812 71. .724 8, ,291 1, ,00 40. ,87 O

ATOM 1073 N SER A 140 50. ,617 72. ,184 8. ,134 1. .00 36. ,90 N

ATOM 1074 CA SER A 140 50. ,857 73. ,047 6. ,978 1. ,00 38. ,30 C

ATOM 1075 CB SER A 140 49. .612 72. .952 6. ,093 1. .00 37. ,48 C

ATOM 1076 OG SER A 140 49. .660 73. .938 5. ,094 1. ,00 39. ,11 O

ATOM 1077 C SER A 140 50. ,991 74. ,529 7. ,417 1. ,00 40. ,09 C

ATOM 1078 O SER A 140 50. ,307 74. .923 8. ,303 1. ,00 38. 59 O

ATOM 1079 N ASN A 141 51. ,772 75. ,389 6. ,745 1. ,00 43. 17 N

ATOM 1080 CA ASN A 141 51. ,682 76. ,834 7. 081 1. 00 43. 67 C

ATOM 1081 CB ASN A 141 52. ,528 77. ,649 6. 139 1. 00 43. 62 C

ATOM 1082 CG ASN A 141 54. .033 77. ,444 6. 394 1. 00 43. 34 C

ATOM 1083 OD1 ASN A 141 54. ,459 76. ,787 7. ,382 1. ,00 39. 12 O

ATOM 1084 ND2 ASN A 141 54. ,827 77. ,979 5. .503 1. ,00 42. 05 N

ATOM 1085 C ASN A 141 50. ,266 77. ,422 7. 111 1. ,00 47. 00 C

ATOM 1086 O ASN A 141 50. ,023 78. ,428 7. 787 1. 00 47. 65 O

ATOM 1087 N ASP A 142 49. ,313 76. ,758 6. 432 1. 00 47. 89 N

ATOM 1088 CA ASP A 142 47. ,963 77. ,295 6. 189 1. 00 47. 27 C

ATOM 1089 CB ASP A 142 47. ,547 77. ,068 4. 699 1. 00 47. 94 C

ATOM 1090 CG ASP A 142 48. 514 77. 708 3. 715 1. 00 54. 07 c

ATOM 1091 OD1 ASP A 142 49. ,167 78. ,775 4. ,018 1. ,00 58. 68 0

ATOM 1092 OD2 ASP A 142 48. ,696 77. ,223 2. 578 1. ,00 63. 93 0

ATOM 1093 C ASP A 142 46. ,940 76. ,704 7. 125 1. 00 45. 70 c

ATOM 1094 O ASP A 142 45. 781 76. .908 6. 933 1. 00 46. 50 o

ATOM 1095 N ASP A 143 47. 343 75. 987 8. 161 1. 00 44. 25 N

ATOM 1096 CA ASP A 143 46. 353 75. 461 9. 100 1. 00 43. 15 c

ATOM 1097 CB ASP A 143 45. 716 74. 176 8. 521 1. 00 45. 04 c

ATOM 1098 CG ASP A 143 44. ,277 73. ,941 8. 950 1. 00 47. 28 c

ATOM 1099 OD1 ASP A 143 43. ,765 74. .572 9. 960 1. 00 50. 98 0

ATOM 1100 OD2 ASP A 143 43. ,589 73. .115 8. 294 1. 00 45. 55 0

ATOM 1101 C ASP A 143 47. ,023 75. ,060 10. 378 1. 00 41. 81 c

ATOM 1102 O ASP A 143 48. 228 75. 148 10. 499 1. 00 39. 95 o

ATOM 1103 N GLU A 144 46. ,210 74. 558 11. 299 1. 00 41. 24 N

ATOM 1104 CA GLU A 144 46. 693 74. 008 12. 539 1. 00 42. 06 C ATOM 1105 CB GLU A 144 45.551 73.836 13.553 1.00 42.81 C

ATOM 1106 CG GLU A 144 44 .519 74 .981 13 .617 1 .00 53 .38 C

ATOM 1107 CD GLU A 144 45 .157 76 .323 14 .034 1 .00 66 .34 C

ATOM 1108 OEl GLU A 144 45 .894 76 .320 15 .072 1 .00 70 .63 O

ATOM 1109 OE2 GLU A 144 44 .954 77 .376 13 .315 1 .00 70 .68 O

ATOM 1110 C GLU A 144 47 .217 72 .651 12 .207 1 .00 41 .72 C

ATOM 1111 O GLU A 144 47 .025 72 .165 11 .060 1 .00 41 .39 O

ATOM 1112 N GLN A 145 47 .732 72 .010 13 .254 1 .00 40 .61 N

ATOM 1113 CA GLN A 145 48 .184 70 .685 13 .266 1 .00 38 .79 C

ATOM 1114 CB GLN A 145 49 .235 70 .526 14 .383 1 .00 38 .62 C

ATOM 1115 CG GLN A 145 50 .095 69 .233 14 .280 1 .00 36 .01 C

ATOM 1116 CD GLN A 145 51 .317 69 .277 15 .199 1 .00 38 .26 C

ATOM 1117 OEl GLN A 145 51 .524 68 .379 16 .060 1 .00 33 .49 O

ATOM 1118 NE2 GLN A 145 52 .102 70 .328 15 .047 1 .00 35 .84 N

ATOM 1119 C GLN A 145 47 .073 69 .697 13 .466 1 .00 40 .59 C

ATOM 1120 O GLN A 145 46 .355 69 .782 14 .472 1 .00 41 .68 O

ATOM 1121 N TYR A 146 47 .023 68 .661 12 .573 1 .00 39 .48 N

ATOM 1122 CA TYR A 146 46 .030 67 .633 12 .614 1 .00 37 .91 C

ATOM 1123 CB TYR A 146 45 .107 67 .795 11 .377 1 .00 38 .80 C

ATOM 1124 CG TYR A 146 44 .030 68 .797 11 .607 1 .00 38 .78 C

ATOM 1125 CDl TYR A 146 42 .801 68 .442 12 .162 1 .00 39 .95 c

ATOM 1126 CE1 TYR A 146 41 .809 69 .460 12 .431 1 .00 39 .12 C

ATOM 1127 CZ TYR A 146 42 .113 70 .790 12 .124 1 .00 40 .89 c

ATOM 1128 OH TYR A 146 41 .185 71 .859 12 .220 1 .00 41 .33 O

ATOM 1129 CE2 TYR A 146 43 .322 71 .097 11 .533 1 .00 39 .95 c

ATOM 1130 CD2 TYR A 146 44 .263 70 .113 11 .308 1 .00 40 .50 c

ATOM 1131 C TYR A 146 46 .623 66 .252 12 .576 1 .00 38 .76 c

ATOM 1132 O TYR A 146 4 .680 66 .037 12 .017 1 .00 37 .92 0

ATOM 1133 N ILE A 147 45 .863 65 .294 13 .067 1 .00 38 .20 N

ATOM 1134 CA ILE A 147 46 .223 63 .892 13, .040 1 .00 39 .56 C

ATOM 1135 CB ILE A 147 46 .087 63 .278 1 .465 1 .00 38 .41 c

ATOM 1136 CGI ILE A 147 46 .777 64 .139 15 .526 1 .00 40 .63 c

ATOM 1137 CDl ILE A 147 46 .534 63 .578 16, .970 1, .00 44. .36 c

ATOM 1138 CG2 ILE A 147 46 .541 61 .804 14, .492 1 .00 38 .77 c

ATOM 1139 C ILE A 147 45 .183 63 .166 12 .141 1 .00 39 .24 c

ATOM 1140 O ILE A 147 43, .970 63 .254 12, .435 1, .00 40, .04 0

ATOM 1141 N TRP A 148 45, .646 62 .452 11, .105 1, .00 36, .98 N

ATOM 1142 CA TRP A 148 44 .811 61 .567 10, .263 1, .00 35, .36 c

ATOM 1143 CB TRP A 148 45, .115 61, .873 8. ,820 1. .00 34. .27 c

ATOM 1144 CG TRP A 148 44, .436 61 .086 7. .738 1. .00 34, .68 c

ATOM 1145 CDl TRP A 148 43, .359 61, .476 6. .960 1, .00 31, .76 c

ATOM 1146 NE1 TRP A 148 43, ,053 60, .476 6. ,057 1. .00 31. ,13 N

ATOM 1147 CE2 TRP A 148 43, .908 59, .427 6. ,226 1. .00 30. ,85 c

ATOM 1148 CD2 TRP A 148 44, .840 59, .799 7. .245 1. .00 31. ,73 c

ATOM 1149 CE3 TRP A 148 45. ,835 58, .886 7. ,619 1. .00 31. ,51 c

ATOM 1150 CZ3 TRP A 148 45, .985 57, .701 6. ,861 1. ,00 34. ,14 c

ATOM 1151 CH2 TRP A 148 45, .066 57, .391 5. ,853 1. ,00 34. ,56 c

ATOM 1152 CZ2 TRP A 148 44. ,042 58. ,278 5. 489 1. ,00 29. ,98 c

ATOM 1153 C TRP A 148 45. ,226 60, ,153 10. ,672 1. ,00 36. .52 c

ATOM 1154 O TRP A 148 46, ,430 59, .919 10. .879 1. ,00 36. ,99 0

ATOM 1155 N GLU A 149 44. ,243 59. ,247 10. 862 1. 00 35. ,17 N

ATOM 1156 CA GLU A 149 44, .482 57. .928 11. 386 1. 00 35. ,59 C

ATOM 1157 CB GLU A 149 44, .011 57. .771 12. ,856 1. .00 35. ,46 C

ATOM 1158 CG GLU A 149 44. ,439 56. ,401 13. 360 1. 00 38. 72 c

ATOM 1159 CD GLU A 149 44. ,473 56. ,234 14. 892 1. 00 44. ,60 c

ATOM 1160 OEl GLU A 149 44. ,629 57. ,197 15. 640 1. 00 42. ,45 0

ATOM 1161 OE2 GLU A 149 44. ,269 55. 089 15. 331 1. 00 52. 11 0

ATOM 1162 C GLU A 149 43. ,760 56. ,864 10. 581 1. 00 36. 15 c

ATOM 1163 0 GLU A 149 42. ,567 57. .002 10. 237 1. 00 34. 71 0

ATOM 1164 N SER A 150 44. 480 55. 778 10. 274 1. 00 35. 79 N

ATOM 1165 CA SER A 150 43. ,873 54. .722 9. 527 1. 00 35. 53 c

ATOM 1166 CB SER A 150 44. ,141 54. .951 8. 056 1. 00 34. 97 c

ATOM 1167 OG SER A 150 43. 852 53. 751 7. 303 1. 00 36. 30 0

ATOM 1168 C SER A 150 44. ,419 53. 371 9. 994 1. 00 35. 44 c

ATOM 1169 O SER A 150 45. ,604 53. ,278 10. 363 1. 00 36. 63 0

ATOM 1170 N ASN A 151 43. 594 52. 336 9. 899 1. 00 35. 74 N

ATOM 1171 CA ASN A 151 43. ,955 50. 933 10. 276 1. 00 37. 72 C

ATOM 1172 CB ASN A 151 43. ,188 50. ,437 11. 545 1. 00 39. 01 C

ATOM 1173 CG ASN A 151 41. 693 50. 366 11. 327 1. 00 43. 94 C

ATOM 1174 OD1 ASN A 151 41. ,163 50. 628 10. 215 1. 00 43. 89 O

ATOM 1175 ND2 ASN A 151 40. ,989 50. ,023 12. 391 1. 00 48. 97 N

ATOM 1176 C ASN A 151 43, 701 50. 015 9. 132 1. 00 34. 74 C

ATOM 1177 O ASN A 151 43. 468 48. 819 9. 291 1. 00 36. 76 O

ATOM 1178 N ALA A 152 43. ,753 50. 611 7. 950 1. 00 35. 84 N

ATOM 1179 CA ALA A 152 43. 511 49. 949 6. 660 1. 00 34. 61 C

ATOM 1180 CB ALA A 152 44, 522 48. 705 6. 438 1. 00 34. 76 C

ATOM 1181 C ALA A 152 42. ,100 49. 475 6. 412 1. 00 33. 66 C ATOM 1182 O ALA A 152 41.899 48.775 5.438 1.00 36.03 O

ATOM 1183 N GLY A 153 41 .132 49 .785 7 .261 1 .00 35 .69 N

ATOM 1184 CA GLY A 153 39 .726 49 .476 6 .949 1 .00 34 .33 C

ATOM 1185 C GLY A 153 39 .160 50 .672 6 .108 1 .00 34 .38 C

ATOM 1186 O GLY A 153 39 .929 51 .627 5 .727 1 .00 33 .62 O

ATOM 1187 N GLY A 154 37 .835 50 .638 5 .897 1 .00 32 .29 N

ATOM 1188 CA GLY A 154 37 .057 51 .632 5 .257 1 .00 30 .16 C

ATOM 1189 C GLY A 154 36 .979 53 .020 5 .811 1 .00 30 .80 C

ATOM 1190 O GLY A 154 36 .594 53 .861 5 .102 1 .00 31 .04 O

ATOM 1191 N SER A 155 37 .464 53 .321 6 .998 1 .00 31 .40 N

ATOM 1192 CA SER A 155 37 .358 54 .664 7 .456 1 .00 32 .55 C

ATOM 1193 CB SER A 155 36 .340 54 .661 8 .642 1 .00 34 .92 C

ATOM 1194 OG SER A 155 35 .093 54 .165 8 .188 1 .00 41 .70 O

ATOM 1195 C SER A 155 38 .604 55 .193 8 .050 1 .00 31 .96 C

ATOM 1196 O SER A 155 39 .364 54 .451 8 .631 1 .00 30 .17 O

ATOM 1197 N PHE A 156 38 .691 56 .515 8 .096 1 .00 32 .00 N

ATOM 1198 CA PHE A 156 39 .747 57 .159 8 .813 1 .00 31 .81 C

ATOM 1199 CB PHE A 156 40 .738 57 .743 7 .782 1 .00 32 .53 C

ATOM 1200 CG PHE A 156 40 .143 58 .684 6 .769 1. .00 27 .45 C

ATOM 1201 CDl PHE A 156 40 .135 60 .045 7 .008 1 .00 28 .84 C

ATOM 1202 CE1 PHE A 156 39 .620 60 .983 6 .049 1 .00 24 .76 C

ATOM 1203 CZ PHE A 156 39 .117 60 .479 4 .823 1 .00 25 .73 C

ATOM 1204 CE2 PHE A 156 39 .099 59 .119 4 .575 1 .00 26 .41 C

ATOM 1205 CD2 PHE A 156 39 .625 58 .199 5 .520 1 .00 27 .41 C

ATOM 1206 C PHE A 156 39 .139 58 .291 9 .624 1 .00 34 .43 C

ATOM 1207 O PHE A 156 37 .969 58 .686 9 .351 1 .00 34 .07 O

ATOM 1208 N THR A 157 39 .927 58 .817 10 .576 1 .00 34 .48 N

ATOM 1209 CA THR A 157 39 .521 59, .910 11, .441 1 .00 36 .22 C

ATOM 1210 CB THR A 157 39 .564 59 .479 12 .922 1, .00 37 .52 C

ATOM 1211 OG1 THR A 157 40 .943 59 .152 13 .304 1 .00 40 .75 O

ATOM 1212 CG2 THR A 157 38, .714 58, .172 13, ,163 1, .00 32 .21 C

ATOM 1213 C THR A 157 40 .501 61, .013 11 .236 1, .00 38 .50 C

ATOM 1214 O THR A 157 41 .651 60 .726 10 .826 1 .00 38 .51 O

ATOM 1215 N VAL A 158 40, .062 62, .261 11, .474 1, .00 38 .38 N

ATOM 1216 CA VAL A 158 40, .872 63, .451 11, .433 1, .00 40 .94 C

ATOM 1217 CB VAL A 158 40, .564 6 .351 10 .205 1 .00 42 .62 C

ATOM 1218 CGI VAL A 158 41, .592 65, .393 10, .010 1, .00 42 .24 C

ATOM 1219 CG2 VAL A 158 40. .605 63, .551 8, .969 1, .00 48 .29 C

ATOM 1220 C VAL A 158 40. .564 64, .170 12 .762 1, .00 41 .22 C

ATOM 1221 O VAL A 158 39. .406 64. .206 13, .186 1, ,00 40, .97 O

ATOM 1222 N THR A 159 41. .603 64. .645 13, .475 1, .00 42 .45 N

ATOM 1223 CA THR A 159 41. ,456 65. ,238 14, .826 1. .00 40, .77 C

ATOM 1224 CB THR A 159 41. ,797 64. ,202 15, .927 1. ,00 42, .10 C

ATOM 1225 OG1 THR A 159 41. .156 62. .949 15, .657 1. .00 39, .08 O

ATOM 1226 CG2 THR A 159 41. ,249 64, ,614 17, ,286 1. ,00 41, .17 C

ATOM 1227 C THR A 159 42. .395 66. ,401 14. .887 1. ,00 42, .38 C

ATOM 1228 O THR A 159 43. .585 66, ,254 14, .498 1. .00 40, .67 O

ATOM 1229 N LEU A 160 41. ,896 67. ,564 15, ,351 1. ,00 42. .16 N

ATOM 1230 CA LEU A 160 42. .796 68. ,657 15, .723 1. .00 43. .62 C

ATOM 1231 CB LEU A 160 42, .054 69, .849 16, .296 1, .00 44 .75 C

ATOM 1232 CG LEU A 160 42. ,872 71. ,083 16. ,673 1. .00 46. .19 C

ATOM 1233 CDl LEU A 160 43. ,190 71. ,866 15. .474 1. ,00 46, .53 C

ATOM 1234 CD2 LEU A 160 42, ,075 71, ,956 17, ,723 1. ,00 44, .73 C

ATOM 1235 C LEU A 160 43. ,874 68. ,085 16. ,690 1. ,00 43, ,97 C

ATOM 1236 O LEU A 160 43. ,573 67. ,257 17. .569 1. ,00 41, .39 O

ATOM 1237 N ASP A 161 45, ,144 68. ,406 16. .413 1. .00 44, .44 N

ATOM 1238 CA ASP A 161 46. ,188 67. ,774 17. ,227 1. .00 46, .80 C

ATOM 1239 CB ASP A 161 47. ,504 67, ,649 16. ,464 1. ,00 46, .37 C

ATOM 1240 CG ASP A 161 48. .497 66, ,678 17, ,130 1. ,00 50, .88 C

ATOM 1241 OD1 ASP A 161 48. .402 66. ,386 18, ,361 1. 00 48, .26 O

ATOM 1242 OD2 ASP A 161 49. ,441 66. ,137 16, ,469 1. ,00 50, .00 O

ATOM 1243 C ASP A 161 46. ,389 68. ,730 18, ,429 1. ,00 48, .61 C

ATOM 1244 O ASP A 161 46. .815 69 . 953 18. ,317 1. 00 45, ,98 O

ATOM 1245 N GLU A 162 46. ,104 68, ,170 19. ,579 1, ,00 51, ,25 N

ATOM 1246 CA GLU A 162 46. ,352 68. ,939 20. ,782 1. ,00 56, .36 C

ATOM 1247 CB GLU A 162 44. 997 69. 588 21. ,313 1. 00 55. .41 C

ATOM 1248 CG GLU A 162 44. ,003 68. ,537 21. ,737 1. 00 62, .65 C

ATOM 1249 CD GLU A 162 42. ,512 68. ,808 21. .378 1. ,00 74, .62 C

ATOM 1250 OEl GLU A 162 42. ,041 70. 005 21. ,348 1. 00 71. .63 O

ATOM 1251 OE2 GLU A 162 41. ,785 67. ,764 21. ,147 1. 00 79. .36 O

ATOM 1252 C GLU A 162 47. ,215 68, ,091 21. ,780 1, ,00 56, .69 C

ATOM 1253 O GLU A 162 47. ,523 68. 577 22. ,825 1. 00 58. ,42 O

ATOM 1254 N VAL A 163 47. ,607 66. ,858 21. ,396 1. 00 57, ,23 N

ATOM 1255 CA VAL A 163 48. ,421 65. ,890 22. .153 1. 00 56, .66 C

ATOM 1256 CB VAL A 163 47. 889 64. 440 22. 021 1. 00 56. ,84 C

ATOM 1257 CGI VAL A 163 46. ,540 64. ,256 22. .676 1. 00 59, .55 C

ATOM 1258 CG2 VAL A 163 47. ,782 64. ,007 20. ,552 1. 00 57, ,22 C ATOM 1259 C VAL A 163 49.952 65. 161 21.784 1.00 57.31 c

ATOM 1260 O VAL A 163 50 .775 65 .372 22 .643 1 .00 57 .82 0

ATOM 1261 N ASN A 164 50 .341 65 .989 20 .526 1 .00 55 .54 N

ATOM 1262 CA ASN A 164 51 .691 65 .593 20 .139 1 .00 53 .15 c

ATOM 1263 CB ASN A 164 51 .762 64 .986 18 .720 1 .00 51 .10 c

ATOM 1264 CG ASN A 164 51 .028 63 .648 18 .577 1 .00 48 .12 c

ATOM 1265 OD1 ASN A 164 51 .451 62 .596 19 .068 1 .00 48 .67 0

ATOM 1266 ND2 ASN A 164 50 .008 63 .659 17 .773 1 .00 40 .67 N

ATOM 1267 C ASN A 164 52 .577 66 .811 20 .190 1 .00 52 .90 C

ATOM 1268 O ASN A 164 52 .127 67 .950 20 .174 1 .00 51 .90 O

ATOM 1269 N GLU A 165 53 .863 66 .544 20 .182 1 .00 53 .74 N

ATOM 1270 CA GLU A 165 54 .860 67 .589 20 .032 1 .00 55 .11 C

ATOM 1271 CB GLU A 165 56 .278 66 .927 20 .004 1 .00 55 .67 C

ATOM 1272 CG GLU A 165 56 .967 66 .816 18 .647 1 .00 64 .36 C

ATOM 1273 CD GLU A 165 58 .072 65 .749 18 .585 1 .00 73 .34 C

ATOM 1274 OEl GLU A 165 57 .797 64 .592 18 .113 1 .00 75 .94 O

ATOM 1275 OE2 GLU A 165 59 .209 66 .064 19 .027 1 .00 74 .12 O

ATOM 1276 C GLU A 165 54 .503 68 .498 18 .811 1 .00 53 .29 C

ATOM 12 7 O GLU A 165 53 .933 68 .056 17 .831 1 .00 51 .63 O

ATOM 1278 N ARG A 166 54 .790 69 .779 18 .892 1 .00 52 .53 N

ATOM 1279 CA ARG A 166 54 .385 70 .653 17 .826 1 .00 52 .81 C

ATOM 1280 CB ARG A 166 54 .284 72 .101 18 .304 1 .00 53 .26 c

ATOM 1281 CG ARG A 166 53 .456 72 .297 19 .541 1 .00 57 .14 c

ATOM 1282 CD ARG A 166 51 .993 72 .306 19 .229 1 .00 61 .89 c

ATOM 1283 NE ARG A 166 51 .487 70 .936 19 .364 1 .00 63 .09 N

ATOM 1284 CZ ARG A 166 50 .258 70 .595 19 .085 1 .00 60 .11 C

ATOM 1285 NH1 ARG A 166 49 .432 71 .539 18 .643 1 .00 58 .82 N

ATOM 1286 NH2 ARG A 166 49 .863 69 .331 19 .293 1 .00 60 .14 N

ATOM 1287 C ARG A 166 55 .449 70 .566 16 .714 1 .00 52 .42 C

ATOM 1288 0 ARG A 166 56 .641 70 .353 17 .013 1 .00 55 .41 O

ATOM 1289 N ILE A 167 55 .037 70 .755 15 .474 1 .00 47 .63 N

ATOM 1290 CA ILE A 167 55. .864 70, .547 14 .334 1 .00 47. .86 C

ATOM 1291 CB ILE A 167 55 .034 69 .550 13 .315 1 .00 49 .33 C

ATOM 1292 CGI ILE A 167 55 .044 68, .087 13 .791 1 .00 52, .97 C

ATOM 1293 CDl ILE A 167 53. .959 67, .188 13, .028 1 .00 56. .98 c

ATOM 1294 CG2 ILE A 167 55, .532 69 .513 11 .941 1 .00 49 .11 c

ATOM 1295 C ILE A 167 55. .916 71, .951 13, .850 1 .00 45. .42 c

ATOM 1296 O ILE A 167 54, .892 72. .610 13, .758 1, .00 47. .09 o

ATOM 1297 N GLY A 168 57. .069 72. ,481 13, .548 1, .00 43. .75 N

ATOM 1298 CA GLY A 168 57, .128 73, .801 12, .939 1, .00 40. .53 C

ATOM 1299 C GLY A 168 56. ,356 73. .723 11. .623 1, .00 41. .23 c

ATOM 1300 O GLY A 168 55. ,463 74. .552 11. .380 1. ,00 41. .66 0

ATOM 1301 N ARG A 169 56. ,604 72. .676 10. .828 1, .00 40. ,13 N

ATOM 1302 CA ARG A 169 55. ,951 72. ,473 9. .512 1, .00 38. ,94 C

ATOM 1303 CB ARG A 169 56. ,516 73. ,482 8. ,504 1. .00 38. .36 C

ATOM 1304 CG ARG A 169 55. 779 73. 556 7. .122 1. .00 33. ,89 C

ATOM 1305 CD ARG A 169 56. ,531 74. ,390 5. ,977 1. .00 32. ,82 C

ATOM 1306 NE ARG A 169 57. ,864 73. 813 5. ,768 1. ,00 36. ,81 N

ATOM 1307 CZ ARG A 169 59. 046 74. 377 6. 086 1. ,00 41. 41 C

ATOM 1308 NH1 ARG A 169 59. 143 75. 625 6. ,589 1. ,00 41. ,41 N

ATOM 1309 NH2 ARG A 169 60. ,153 73. 666 5. ,884 1. .00 41. 40 N

ATOM 1310 C ARG A 169 56. 381 71. 100 9. 005 1. ,00 38. 23 C

ATOM 1311 0 ARG A 169 57. 567 70. 708 9. 233 1. 00 38. 13 O

ATOM 1312 N GLY A 170 55. ,494 70. 431 8. 257 1. .00 36. 68 N

ATOM 1313 CA GLY A 170 55. 797 69. 163 7. 558 1. 00 33. 64 C

ATOM 1314 C GLY A 170 54. 977 68. 071 8. 217 1. 00 32. 47 C

ATOM 1315 0 GLY A 170 53. 960 68. 418 8. 788 1. 00 34. 63 O

ATOM 1316 N THR A 171 55. 444 66. 840 8. 302 1. 00 31. 01 N

ATOM 1317 CA THR A 171 54. 559 65. 767 8. 534 1. 00 32. 44 C

ATOM 1318 CB THR A 171 54. 115 65. 206 7. 155 1. 00 34. 38 C

ATOM 1319 OG1 THR A 171 53. 250 66. 158 6. 505 1. 00 35. 63 O

ATOM 1320 CG2 THR A 171 53. 288 63. 981 7. 304 1. 00 28. 62 C

ATOM 1321 C THR A 171 55. 278 64. 666 9. 178 1. 00 34. 25 C

ATOM 1322 O THR A 171 56. 400 64. 381 8. 812 1. 00 36. 85 O

ATOM 1323 N ILE A 172 54. 634 63. 942 10. 086 1. 00 34. 58 N

ATOM 1324 CA ILE A 172 55. 280 62. 733 10. 605 1. 00 34. 16 C

ATOM 1325 CB ILE A 172 55. 294 62. 849 12. 186 1. 00 34. 87 C

ATOM 1326 CGI ILE A 172 56. 194 63. 999 12. 651 1. 00 33. 09 C

ATOM 1327 CDl ILE A 172 55. 960 64. 354 14. 146 1. 00 39. 83 C

ATOM 1328 CG2 ILE A 172 55. 596 61. 562 12. 880 1. 00 29. 63 C

ATOM 1329 C ILE A 172 54. 394 61. 608 10. 277 1. 00 35. 63 C

ATOM 1330 O ILE A 172 53. 187 61. 714 10. 552 1. 00 37. 37 O

ATOM 1331 N LEU A 173 54. 932 60. 505 9. 772 1. 00 34. 65 N

ATOM 1332 CA LEU A 173 54. 157 59. 282 9. 606 1. 00 35. 61 C

ATOM 1333 CB LEU A 173 54. 488 58. 528 8. 287 1. 00 31. 43 C

ATOM 1334 CG LEU A 173 53. 567 58. 809 7. 100 1. 00 35. 22 C

ATOM 1335 CDl LEU A 173 53. 402 60. 314 6. 794 1. 00 32. 36 C ATOM 1336 CD2 LEU A 173 54.105 58.102 5.820 1.00 37.18 c

ATOM 1337 C LEU A 173 54 .515 58 .413 10 .839 1 .00 36 .28 c

ATOM 1338 O LEU A 173 55 .647 57 .988 10 .995 1 .00 36 .83 0

ATOM 1339 N ARG A 174 53 .559 58 .122 11 .703 1 .00 37 .66 N

ATOM 1340 CA ARG A 174 53 .851 57 .296 12 .863 1 .00 36 .89 C

ATOM 1341 CB ARG A 174 53 .207 57 .891 14 .115 1 .00 38 .11 C

ATOM 1342 CG ARG A 174 53 .251 57 .007 15 .393 1 .00 38 .74 C

ATOM 1343 CD ARG A 174 52 .702 57 .744 16 .667 1 .00 38 .43 C

ATOM 1344 NE ARG A 174 53 .451 59 .003 16 .951 1 .00 40 .48 N

ATOM 1345 CZ ARG A 174 52 .977 60 .063 17 .641 1 .00 40 .08 C

ATOM 1346 NH1 ARG A 174 51 .719 60 .110 18 .123 1 .00 39 .37 N

ATOM 1347 NH2 ARG A 174 53 .731 61 .115 17 .782 1 .00 34 .70 N

ATOM 1348 C ARG A 174 53 .305 55 .978 12 .550 1 .00 35 .84 C

ATOM 1349 O ARG A 174 52 .107 55 .797 12 .598 1 .00 33 .90 O

ATOM 1350 N LEU A 175 54 .183 55 .016 12 .263 1 .00 35 .72 N

ATOM 1351 CA LEU A 175 53 .726 53 .675 11 .959 1 .00 36 .24 C

ATOM 1352 CB LEU A 175 54 .541 52 .992 10 .832 1 .00 36 .90 C

ATOM 1353 CG LEU A 175 55 .125 53 .721 9 .603 1 .00 41 .32 C

ATOM 1354 CDl LEU A 175 55 .942 52 .702 8 .654 1 .00 34 .77 C

ATOM 1355 CD2 LEU A 175 54 .173 54 .627 8 .876 1 .00 37 .51 C

ATOM 1356 C LEU A 175 53 .704 52 .777 13 .169 1 .00 35 .49 C

ATOM 1357 0 LEU A 175 54 .674 52 .785 13 .947 1 .00 37 .63 O

ATOM 1358 N PHE A 176 52 .662 51 .940 13 .268 1 .00 34 .74 N

ATOM 1359 CA PHE A 176 52 .446 51 .024 14 .371 1 .00 33 .13 C

ATOM 1360 CB PHE A 176 50 .984 51 .120 15 .020 1 .00 32 .84 C

ATOM 1361 CG PHE A 176 50 .719 52 .443 15 .738 1 .00 35, .27 C

ATOM 1362 CDl PHE A 176 50 .449 53 .600 15 .008 1 .00 34 .78 C

ATOM 1363 CE1 PHE A 176 50 .306 54 .829 15 .590 1 .00 29 .23 C

ATOM 1364 CZ PHE A 176 50 .438 54 .961 16 .975 1, .00 36 .32 C

ATOM 1365 CE2 PHE A 176 50, .710 53, .852 17, .754 1, .00 35, .91 C

ATOM 1366 CD2 PHE A 176 50 .841 52 .565 17 .133 1 .00 37 .54 C

ATOM 1367 C PHE A 176 52 .754 49, .726 13 .730 1, .00 33, .26 C

ATOM 1368 0 PHE A 176 51, .925 49, .112 13 .051 1, .00 34, .90 O

ATOM 1369 N LEU A 177 53, .940 49. .209 13, .978 1. .00 34, .76 N

ATOM 1370 CA LEU A 177 54 .491 48. .068 13 .183 1. .00 34, .72 C

ATOM 1371 CB LEU A 177 56, .022 47. .866 13, .474 1. .00 36, .55 C

ATOM 1372 CG LEU A 177 56, .963 49. .041 13, ,144 1. .00 34, .96 C

ATOM 1373 CDl LEU A 177 58. .458 48. .551 13, .315 1. ,00 40. ,27 C

ATOM 1374 CD2 LEU A 177 56. .733 49. .375 11, .645 1. .00 28. .20 C

ATOM 1375 C LEU A 177 53. .790 46. .810 13, .499 1. .00 35, .80 C

ATOM 1376 0 LEU A 177 53. ,427 46. .699 14. .591 1. ,00 36, ,21 O

ATOM 1377 N LYS A 178 53. ,610 45. ,865 12, .573 1. ,00 37. ,82 N

ATOM 1378 CA LYS A 178 53, .090 44. .535 12, .908 1. .00 42, .79 C

ATOM 1379 CB LYS A 178 52, .742 43. ,711 11, .643 1. .00 42. .16 C

ATOM 1380 CG LYS A 178 52, .031 44. ,487 10, .506 1. ,00 42. .82 C

ATOM 1381 CD LYS A 178 52. ,104 43. ,760 9. ,140 1. ,00 33. ,63 C

ATOM 1382 CE LYS A 178 50, .954 44. .124 8, .230 1. ,00 34. .14 C

ATOM 1383 NZ LYS A 178 50. .933 43. ,401 6, .843 1. ,00 37, ,10 N

ATOM 1384 C LYS A 178 54. ,109 43. ,689 13, .800 1. ,00 45. ,07 C

ATOM 1385 0 LYS A 178 55. ,326 43. ,917 13. ,775 1. 00 46. ,54 O

ATOM 1386 N ASP A 179 53, ,605 42. ,681 14, .506 1. ,00 46. .91 N

ATOM 1387 CA ASP A 179 54. ,416 41. ,820 15, .401 1. ,00 48. .42 C

ATOM 1388 CB ASP A 179 53. ,540 40. ,708 16. ,111 1. 00 48. .03 C

ATOM 1389 CG ASP A 179 52. ,643 41. 266 17. ,232 1. 00 53. 88 C

ATOM 1390 OD1 ASP A 179 53. ,024 42. ,294 17. .867 1. ,00 60. ,78 O

ATOM 1391 OD2 ASP A 179 51. ,502 40. ,771 17. ,555 1. 00 59. ,46 O

ATOM 1392 C ASP A 179 55. ,560 41. ,161 14. ,616 1. 00 48. ,14 C

ATOM 1393 0 ASP A 179 56. ,620 41. 002 15. ,110 1. 00 47. 63 O

ATOM 1394 N ASP A 180 55. ,333 40. ,745 13. .392 1. 00 49. ,26 N

ATOM 1395 CA ASP A 180 56. ,422 40. ,081 12. ,666 1. 00 48. ,71 C

ATOM 1396 CB ASP A 180 55. ,846 39. 015 11. ,743 1. 00 50. 41 C

ATOM 1397 CG ASP A 180 54. 878 39. 551 10, 695 1. 00 55. 04 C

ATOM 1398 OD1 ASP A 180 54. ,004 40. 410 10. ,988 1. 00 63. ,68 O

ATOM 1399 OD2 ASP A 180 54. 877 39. 101 9, ,511 1. 00 63. 48 O

ATOM 1400 C ASP A 180 57. 425 41. 018 11. ,954 1. 00 47. 40 C

ATOM 1401 0 ASP A 180 58. 335 40. 527 11. ,280 1. 00 49. 52 O

ATOM 1402 N GLN A 181 57. ,287 42. 355 12, ,145 1. 00 44. ,17 N

ATOM 1403 CA GLN A 181 58. 016 43. 410 11. ,348 1. 00 41. 52 C

ATOM 1404 CB GLN A 181 57. 108 44. 210 10. ,363 1. 00 38. 30 C

ATOM 1405 CG GLN A 181 56. 352 43. 298 9. 487 1. 00 32. 95 C

ATOM 1406 CD GLN A 181 57. ,203 42. 400 8. ,590 1. 00 39. ,76 C

ATOM 1407 OEl GLN A 181 56. ,750 41. 343 8. ,256 1. 00 50. 79 O

ATOM 1408 NE2 GLN A 181 58. 312 42. 851 8. ,102 1. 00 35. 22 N

ATOM 1409 C GLN A 181 58. 767 44. 352 12. 258 1. 00 41. 31 C

ATOM 1410 0 GLN A 181 59. ,150 45. 483 11. ,872 1. 00 41. 76 O

ATOM 1411 N LEU A 182 59. 018 43. 834 13. ,460 1. 00 41. 71 N

ATOM 1412 CA LEU A 182 59. 758 44. 528 14. 485 1. 00 44. 01 C ATOM 1413 CB LEU A 182 59.542 43.871 15.901 1.00 44.94 c

ATOM 1414 CG LEU A 182 58 .069 43 .957 16 .401 1 .00 47 .77 c

ATOM 1415 CDl LEU A 182 57 .955 43 .616 17 .967 1 .00 48 .41 c

ATOM 1416 CD2 LEU A 182 57 .430 45 .416 16 .118 1 .00 39 .92 c

ATOM 1417 C LEU A 182 61 .224 44 .795 14 .113 1 .00 43 .19 c

ATOM 1418 O LEU A 182 61 .823 45 .756 14 .619 1 .00 43 .34 o

ATOM 1419 N GLU A 183 61 .754 44 .065 13 .135 1 .00 43 .49 N

ATOM 1420 CA GLU A 183 63 .092 44 .389 12 .671 1 .00 43 .21 C

ATOM 1421 CB GLU A 183 63 .523 43 .462 11 .520 1 .00 44 .88 C

ATOM 1422 CG GLU A 183 63 .284 43 .999 10 .092 1 .00 46 .82 C

ATOM 1423 CD GLU A 183 63 .096 42 .866 9 .125 1 .00 42 .79 c

ATOM 1424 OEl GLU A 183 62 .298 41 .938 9 .447 1 .00 42 .24 o

ATOM 1425 OE2 GLU A 183 63 .782 42 .866 8 .047 1 .00 50 .45 0

ATOM 1426 C GLU A 183 63 .241 45 .825 12 .311 1 .00 44 .53 c

ATOM 1427 O GLU A 183 64 .367 46 .365 12 .499 1 .00 45 .72 o

ATOM 1428 N TYR A 184 62 .157 46 .531 11 .858 1 .00 43 .35 N

ATOM 1429 CA TYR A 184 62 .392 47 .903 11 .336 1 .00 41 .00 C

ATOM 1430 CB TYR A 184 61 .455 48 .405 10 .206 1 .00 39 .37 C

ATOM 1431 CG TYR A 184 61 .472 47 .456 9 .056 1 .00 34 .45 C

ATOM 1432 CDl TYR A 184 62 .465 47 .533 8 .082 1 .00 31 .21 c

ATOM 1433 CE1 TYR A 184 62 .504 46 .589 6 .994 1 .00 31 .81 c

ATOM 1434 CZ TYR A 184 61 .600 45 .547 6 .950 1 .00 32 .92 c

ATOM 1435 OH TYR A 184 61 .667 44 .597 5 .903 1 .00 36 .79 o

ATOM 1436 CE2 TYR A 184 60 .585 45 .459 7 .940 1 .00 31 .81 c

ATOM 1437 CD2 TYR A 184 60, .564 46 .424 9 .002 1 .00 27 .77 c

ATOM 1438 C TYR A 184 62 .533 48 .867 12 .410 1 .00 43 .55 c

ATOM 1439 O TYR A 184 62 .591 50 .061 12 .139 1 .00 45 .37 0

ATOM 1440 N LEU A 185 62 .664 48 .385 13 .644 1 .00 46 .19 N

ATOM 1441 CA LEU A 185 63, .053 49 .241 14 .784 1 .00 47, .85 C

ATOM 1442 CB LEU A 185 62, .451 48 .635 16 .053 1 .00 48, .53 c

ATOM 1443 CG LEU A 185 60, .880 48, .503 16 .152 1 .00 48, .84 c

ATOM 1444 CDl LEU A 185 60 .409 47, .487 17 .337 1 .00 47, .87 c

ATOM 1445 CD2 LEU A 185 60, .195 49 .863 16 .274 1 .00 46, .92 c

ATOM 1446 C LEU A 185 64, .589 49, .384 14 .957 1, .00 48, ,94 c

ATOM 1447 O LEU A 185 65. .085 50, .328 15 .548 1, .00 49, .70 o

ATOM 1448 N GLU A 186 65. .343 48, .416 14 .464 1, .00 50. .39 N

ATOM 1449 CA GLU A 186 66. .794 48 .331 14 .702 1 .00 50. .90 C

ATOM 1450 CB GLU A 186 67, .206 46, .864 14 .462 1, .00 50, .38 c

ATOM 1451 CG GLU A 186 66, .453 45, .760 15 .236 1, .00 56. .09 c

ATOM 1452 CD GLU A 186 66. .411 44, .389 14, .501 1. .00 65. ,96 c

ATOM 1453 OEl GLU A 186 66. ,983 44. ,262 13, .368 1. .00 71. ,31 o

ATOM 1454 OE2 GLU A 186 65. .830 43. .385 15 .032 1, .00 69. .39 o

ATOM 1455 C GLU A 186 67. .519 49, .359 13 .751 1, .00 51. .27 c

ATOM 1456 O GLU A 186 67. .334 49, .279 12, .527 1. .00 50. ,25 o

ATOM 1457 N GLU A 187 68. .262 50, .342 14, .286 1, .00 52. ,03 N

ATOM 1458 CA GLU A 187 69. ,011 51. .328 13. .475 1. ,00 53. ,70 c

ATOM 1459 CB GLU A 187 70, .060 52. .149 14. .297 1. .00 54, .16 c

ATOM 1460 CG GLU A 187 69. .665 52, .662 15, .677 1, .00 63. ,93 c

ATOM 1461 CD GLU A 187 69. ,975 54, .173 15, .866 1, .00 74. ,64 c

ATOM 1462 OEl GLU A 187 70. ,994 54. .669 15, .287 1. .00 78. ,79 o

ATOM 1463 OE2 GLU A 187 69. .179 54. ,886 16. .567 1. ,00 77. ,62 0

ATOM 1464 C GLU A 187 69. .794 50. ,638 12. .341 1. ,00 53. ,15 c

ATOM 1465 O GLU A 187 69. .932 51, .168 11. .191 1, .00 51. ,65 o

ATOM 1466 N LYS A 188 70. ,322 49, .466 12, .662 1. ,00 52. ,17 N

ATOM 1467 CA LYS A 188 71. .178 48. .789 11, .676 1. ,00 53. ,68 C

ATOM 1468 CB LYS A 188 71. .950 47. ,537 12, ,261 1. .00 54. ,74 c

ATOM 1469 CG LYS A 188 72. .938 46. ,775 11. ,335 1. ,00 60. 41 c

ATOM 1470 CD LYS A 188 74, ,401 46, .553 11. .985 1. ,00 70. ,87 c

ATOM 1471 CE LYS A 188 75. ,261 45, .425 11, .287 1. ,00 72. ,70 c

ATOM 1472 NZ LYS A 188 74. ,394 44, ,198 10, .875 1. ,00 70. 01 N

ATOM 1473 C LYS A 188 70. ,303 48. ,446 10. ,505 1. ,00 50. 91 C

ATOM 1474 O LYS A 188 70. ,664 48, ,749 9. ,411 1. ,00 51. 91 O

ATOM 1475 N ARG A 189 69. ,155 47. .818 10, .737 1. ,00 49. ,41 N

ATOM 1476 CA ARG A 189 68. ,280 47, ,365 9. .653 1. ,00 46. ,38 C

ATOM 1477 CB ARG A 189 67. ,104 46. ,546 10, .211 1. ,00 46. 54 C

ATOM 1478 CG ARG A 189 66. .146 46. .023 9. ,149 1. ,00 46. 35 C

ATOM 1479 CD ARG A 189 66. .774 45. 037 8. ,226 1. ,00 48. 44 C

ATOM 1480 NE ARG A 189 65. ,759 44. .417 7. .386 1. ,00 46. 65 N

ATOM 1481 CZ ARG A 189 65. .864 44. .373 6. .069 1. ,00 49. 74 C

ATOM 1482 NH1 ARG A 189 66. .963 44. .875 5. ,469 1. ,00 50. 63 N

ATOM 1483 NH2 ARG A 189 64. ,865 43. ,894 5. ,331 1, ,00 47. 74 N

ATOM 1484 C ARG A 189 67. ,863 48. ,570 8. ,803 1. 00 45. 99 C

ATOM 1485 O ARG A 189 67. 906 48, 524 7. ,568 1. 00 45. 15 O

ATOM 1486 N ILE A 190 67. ,631 49, ,706 9, .471 1. ,00 44. ,71 N

ATOM 1487 CA ILE A 190 67. ,172 50. ,878 8. ,779 1. ,00 44. 90 C

ATOM 1488 CB ILE A 190 66. ,620 51. ,923 9. ,796 1. 00 43. 44 C

ATOM 1489 CGI ILE A 190 65. ,280 51. ,478 10. ,348 1. 00 45. 64 C ATOM 1490 CDl ILE A 190 65.029 51.865 11.802 1.00 43.10 c

ATOM 1491 CG2 ILE A 190 66 .439 53 .197 9 .174 1 .00 40 .39 c

ATOM 1492 C ILE A 190 68 .257 51 .446 7 .834 1 .00 46 .52 c

ATOM 1493 O ILE A 190 67 .970 51 .907 6 .678 1 .00 46 .07 0

ATOM 1494 N LYS A 191 69 .490 51 .476 8 .333 1 .00 47 .04 N

ATOM 1495 CA LYS A 191 70 .614 51 .988 7 .544 1 .00 47 .56 C

ATOM 1496 CB LYS A 191 71 .915 52 .021 8 .349 1 .00 48 .56 C

ATOM 1497 CG LYS A 191 71 .983 53 .295 9 .135 1 .00 55 .26 C

ATOM 1498 CD LYS A 191 72 .572 53 .061 10 .544 1 .00 63 .03 C

ATOM 1499 CE LYS A 191 72 .987 54 .444 11 .173 1 .00 65 .36 C

ATOM 1500 NZ LYS A 191 73 .610 54 .250 12 .578 1 .00 67 .34 N

ATOM 1501 C LYS A 191 70 .776 51 .105 6 .361 1 .00 45 .63 C

ATOM 1502 O LYS A 191 71 .016 51 .660 5 .269 1 .00 46 .30 O

ATOM 1503 N GLU A 192 70 .570 49 .784 6 .507 1 .00 43 .74 N

ATOM 1504 CA GLU A 192 70 .799 48 .922 5 .349 1 .00 46 .44 C

ATOM 1505 CB GLU A 192 70 .724 47 .393 5 .599 1 .00 47 .69 C

ATOM 1506 CG GLU A 192 70 .964 46 .912 7 .016 1 .00 55 .56 C

ATOM 1507 CD GLU A 192 70 .946 45 .369 7 .178 1 .00 67 .86 C

ATOM 1508 OEl GLU A 192 69 .893 44 .705 6 .780 1 .00 66 .65 0

ATOM 1509 OE2 GLU A 192 71 .995 44 .837 7 .732 1 .00 68 .51 0

ATOM 1510 C GLU A 192 69 .753 49 .231 4 .290 1 .00 47 .13 c

ATOM 1511 O GLU A 192 70 .078 49 .266 3 .089 1 .00 47 .53 0

ATOM 1512 N VAL A 193 68 .491 49 .438 4 .741 1 .00 45 .29 N

ATOM 1513 CA VAL A 193 67 .418 49 .573 3 .791 1 .00 42 .47 C

ATOM 1514 CB VAL A 193 66 .012 49 .494 4 .465 1 .00 42 .77 C

ATOM 1515 CGI VAL A 193 64 .871 49 .736 3 .360 1 .00 41 .04 C

ATOM 1516 CG2 VAL A 193 65 .833 48 .183 5 .119 1 .00 39 .88 C

ATOM 1517 C VAL A 193 67 .579 50 .893 3 .016 1 .00 41 .84 c

ATOM 1518 O VAL A 193 67, .346 50, .934 1 .845 1 .00 39 .72 o

ATOM 1519 N ILE A 194 67 .948 51 .962 3 .689 1 .00 41 .49 N

ATOM 1520 CA ILE A 194 68 .157 53, .248 3 .041 1 .00 43 .33 C

ATOM 1521 CB ILE A 194 68, .485 54, .228 4 .192 1 .00 42 .04 C

ATOM 1522 CGI ILE A 194 67, .271 54, .608 5, .024 1 .00 41, .94 c

ATOM 1523 CDl ILE A 194 67 .743 55, .432 6 .234 1 .00 40 .65 c

ATOM 1524 CG2 ILE A 194 69, .313 55, .373 3, .740 1 .00 40 .96 c

ATOM 1525 C ILE A 194 69, .400 53. .174 2, .114 1 .00 46. .95 c

ATOM 1526 O ILE A 194 69, .489 53. .825 1, .100 1, .00 47. .23 o

ATOM 1527 N LYS A 195 70. ,428 52. .419 2, .507 1, .00 49. .98 N

ATOM 1528 CA LYS A 195 71. .588 52, .324 1, .615 1 .00 52. .25 C

ATOM 1529 CB LYS A 195 72, .838 51. ,592 2, .255 1, .00 53. .30 C

ATOM 1530 CG LYS A 195 74. ,083 52. ,480 2. .137 1, .00 60. ,24 C

ATOM 1531 CD LYS A 195 75. ,180 51. ,765 1. .321 1. .00 70. ,81 C

ATOM 1532 CE LYS A 195 76, .018 50. ,766 2. .202 1. .00 74. .89 C

ATOM 1533 NZ LYS A 195 77. ,372 50. ,696 1. ,573 1, .00 77. .32 N

ATOM 1534 C LYS A 195 71. ,138 51. 638 0. ,350 1. .00 49. ,73 C

ATOM 1535 O LYS A 195 71. ,392 52. 135 -0. ,732 1. ,00 47. 89 O

ATOM 1536 N ARG A 196 70. .483 50. 498 0. ,533 1. ,00 50. 59 N

ATOM 1537 CA ARG A 196 69. ,927 49. 709 -0. ,575 1. .00 52. ,96 C

ATOM 1538 CB ARG A 196 69. ,283 48. 442 -0. ,053 1. ,00 53. ,01 C

ATOM 1539 CG ARG A 196 69. ,284 47. 178 -1. ,020 1. ,00 61. 31 C

ATOM 1540 CD ARG A 196 68. ,163 47. 137 -2. 067 1. ,00 70. 44 C

ATOM 1541 NE ARG A 196 68. ,392 46. ,316 -3. .283 1. ,00 78. ,08 N

ATOM 1542 CZ ARG A 196 68. .471 46. ,797 -4. ,537 1. ,00 80. ,44 C

ATOM 1543 NH1 ARG A 196 68. .375 48. 111 -4. ,803 1. ,00 82. 39 N

ATOM 1544 NH2 ARG A 196 68. ,659 45. 962 -5. 539 1. ,00 80. 15 N

ATOM 1545 C ARG A 196 69. ,036 50. ,498 -1. ,588 1. .00 53. .40 C

ATOM 1546 O ARG A 196 69. ,154 50. 215 -2. ,774 1. ,00 54. ,50 O

ATOM 1547 N HIS A 197 68. .261 51. 540 -1. ,177 1. ,00 52. 49 N

ATOM 1548 CA HIS A 197 67. 146 52. 069 -2. 034 1. ,00 52. 93 C

ATOM 1549 CB HIS A 197 65. 758 51. 557 -1. 622 1. 00 50. 40 C

ATOM 1550 CG HIS A 197 65. .633 50. 076 -1. ,484 1. .00 48. 65 C

ATOM 1551 ND1 HIS A 197 65. 389 49. 232 -2, 563 1. .00 51. 52 N

ATOM 1552 CE1 HIS A 197 65. 264 47. 984 -2. 130 1. 00 46. 56 C

ATOM 1553 NE2 HIS A 197 65. 398 47. 989 -0. 804 1. 00 47. 98 N

ATOM 1554 CD2 HIS A 197 65. ,624 49. 285 -0. ,380 1. .00 43. 29 C

ATOM 1555 C HIS A 197 67. 002 53. 584 -2. 233 1. 00 53. 92 C

ATOM 1556 O HIS A 197 66. 368 54. 065 -3. 218 1. 00 54. 27 O

ATOM 1557 N SER A 198 67. 624 54. 333 -1. 341 1. 00 55. 28 N

ATOM 1558 CA SER A 198 67. 333 55. 734 -1. 203 1. 00 56. 70 C

ATOM 1559 CB SER A 198 66. 440 55. ,911 0. 048 1. .00 56. 09 C

ATOM 1560 OG SER A 198 65. 241 55. 080 -0. 022 1. 00 52. 39 O

ATOM 1561 C SER A 198 68. 661 56. 498 -1. 108 1. 00 60. 49 C

ATOM 1562 O SER A 198 68. 731 57. 711 -0. 712 1. 00 60. 00 O

ATOM 1563 N GLU A 199 69. 731 55. 808 -1. 519 1. 00 63. 46 N

ATOM 1564 CA GLU A 199 71. 069 56. 425 -1. 543 1. 00 66. 27 C

ATOM 1565 CB GLU A 199 72. 043 55. 428 -2. 133 1. 00 67. 99 C

ATOM 1566 CG GLU A 199 73. 439 55. 388 -1. 514 1. 00 74. 54 C 005/056593

ATOM 1567 CD GLU A 199 74 .306 54 .364 -2 .264 1 .00 80 .14 c

ATOM 1568 OEl GLU A 199 74 .232 54 .357 -3 .530 1 .00 79 .82 O

ATOM 1569 0E2 GLU A 199 74 .986 53 .526 -1 .596 1 .00 82 .78 O

ATOM 1570 C GLU A 199 71 .108 57 .740 -2 .313 1 .00 65 .75 c

ATOM 1571 0 GLU A 199 71 .752 58 .662 -1 .875 1 .00 65 .13 O

ATOM 1572 N PHE A 200 70 .355 57 .834 -3 .415 1 .00 67 .33 N

ATOM 1573 CA PHE A 200 70 .352 59 .006 -4 .326 1 .00 69 .02 C

ATOM 1574 CB PHE A 200 69 .815 58 .590 -5 .724 1 .00 71 .84 C

ATOM 1575 CG PHE A 200 70 .869 58 .108 -6 .731 1 .00 78 .46 C

ATOM 1576 CDl PHE A 200 71 .355 58 .991 -7 .742 1 .00 84 .67 C

ATOM 1577 CE1 PHE A 200 72 .315 58 .559 -8 .725 1 .00 87 .00 c

ATOM 1578 CZ PHE A 200 72 .774 57 .207 -8 .702 1 .00 88 .79 c

ATOM 1579 CE2 PHE A 200 72 .258 56 .291 -7 .700 1 .00 87 .34 c

ATOM 1580 CD2 PHE A 200 71 .303 56 .751 -6 .738 1 .00 84 .54 c

ATOM 1581 C PHE A 200 69 .445 60 .185 -3 .846 1 .00 67 .55 c

ATOM 1582 O PHE A 200 69 .250 61 .187 -4 .571 1 .00 61 .96 0

ATOM 1583 N VAL A 201 68 .884 60 .094 -2 .643 1 .00 64 .98 N

ATOM 1584 CA VAL A 201 67 .905 61 .116 -2 .171 1 .00 61 .44 C

ATOM 1585 CB VAL A 201 61 .005 60 .528 -0 .987 1 .00 61 .24 C

ATOM 1586 CGI VAL A 201 66 .135 61 .600 -0 .400 1 .00 60 .73 C

ATOM 1587 CG2 VAL A 201 66 .120 59 .367 -1 .531 1 .00 59 .07 c

ATOM 1588 C VAL A 201 68 .528 62 .491 -1 .866 1 .00 58 .57 c

ATOM 1589 O VAL A 201 69 .505 62 .567 -1 .182 1 .00 58 .24 0

ATOM 1590 N ALA A 202 67 .956 63 .576 -2 .340 1 .00 57 .16 N

ATOM 1591 CA ALA A 202 68 .624 64 .889 -2 .241 1 .00 56 .60 C

ATOM 1592 CB ALA A 202 68, .156 65 .812 -3 .421 1, .00 57 .81 C

ATOM 1593 C ALA A 202 68, .513 65 .695 -0 .925 1 .00 56 .15 C

ATOM 1594 0 ALA A 202 68, .832 66 .881 -0 .920 1 .00 57 .51 O

ATOM 1595 N TYR A 203 67, .999 65 .114 0 .162 1, .00 54 .00 N

ATOM 1596 CA TYR A 203 67, .799 65 .840 1 .401 1, .00 49 .97 C

ATOM 1597 CB TYR A 203 66. .321 65 .980 1 .735 1, .00 49, .21 C

ATOM 1598 CG TYR A 203 65. .591 66 .869 0 .760 1, .00 45 .88 C

ATOM 1599 CDl TYR A 203 65. .680 68 .217 0 .836 1. .00 40 .57 C

ATOM 1600 CE1 TYR A 203 65. .108 69 .018 -0 .119 1, .00 41 .11 C

ATOM 1601 CZ TYR A 203 64. .344 68 .493 -1 .144 1, .00 37 .15 C

ATOM 1602 OH TYR A 203 63, .735 6 .355 -2 .101 1, .00 44 .50 O

ATOM 1603 CE2 TYR A 203 64, .233 61 .191 -1 .254 1, .00 39 .44 c

ATOM 1604 CD2 TYR A 203 64, ,870 66 .340 -0 .303 1. .00 44. .91 c

ATOM 1605 C TYR A 203 68, ,533 64, .944 2, .352 1. ,00 50, .46 c

ATOM 1606 O TYR A 203 68. ,673 63, .762 2, .053 1. ,00 51. .33 0

ATOM 1607 N PRO A 204 69 . ,100 65, .479 3 .426 1. ,00 49. .54 N

ATOM 1608 CA PRO A 204 69. .737 64, .607 4 .397 1. .00 50. .15 C

ATOM 1609 CB PRO A 204 70. .300 65, .584 5, .463 1. ,00 49. .94 C

ATOM 1610 CG PRO A 204 69, ,506 66, .764 5, .338 1, ,00 48, .91 C

ATOM 1611 CD PRO A 204 69. .191 66, .906 3, .816 1. ,00 49, .98 C

ATOM 1612 C PRO A 204 68. .668 63, .727 5, .015 1. ,00 49, .92 C

ATOM 1613 O PRO A 204 67. ,568 64, .240 5, .250 1. ,00 51, .14 0

ATOM 1614 N ILE A 205 68. .992 62, .478 5, .291 1. .00 48. ,55 N

ATOM 1615 CA ILE A 205 68. ,147 61, .655 6, .091 1. .00 48. ,80 C

ATOM 1616 CB ILE A 205 67. .897 60. .285 5, ,364 1, ,00 48. ,46 C

ATOM 1617 CGI ILE A 205 67. ,205 60, .491 3, .970 1. ,00 46. .21 C

ATOM 1618 CDl ILE A 205 67, .174 59. .183 3, .177 1. ,00 43, .26 C

ATOM 1619 CG2 ILE A 205 67, ,144 59. ,280 6. ,323 1, ,00 46, .43 C

ATOM 1620 C ILE A 205 68. 768 61. ,435 7. .481 1. 00 49. ,79 C

ATOM 1621 0 ILE A 205 69 . ,707 60, .695 7. .632 1. 00 50. ,25 o

ATOM 1622 N GLN A 206 68. 232 62. ,090 8. .494 1. 00 50. ,59 N

ATOM 1623 CA GLN A 206 68. ,729 61. ,983 9. ,841 1. 00 50. ,34 C

ATOM 1624 CB GLN A 206 68. 353 63. ,196 10. ,608 1, 00 48. ,74 C

ATOM 1625 CG GLN A 206 68. .727 64, .444 9. ,901 1. 00 47. ,25 C

ATOM 1626 CD GLN A 206 68. ,192 65. .636 10. ,647 1. 00 53. ,04 C

ATOM 1627 OEl GLN A 206 67. ,475 65, .508 11. ,701 1. ,00 57. ,04 O

ATOM 1628 NE2 GLN A 206 68. ,490 66. .802 10. .128 1. ,00 52. ,73 N

ATOM 1629 C GLN A 206 68. ,150 60. .787 10. ,506 1. 00 52. ,59 C

ATOM 1630 O GLN A 206 67. ,005 60. .521 10. .408 1. ,00 53. ,94 O

ATOM 1631 N LEU A 207 68. ,980 60, .010 11. .137 1. 00 55. ,29 N

ATOM 1632 CA LEU A 207 68. ,531 58, .959 11. .989 1. ,00 58. ,13 C

ATOM 1633 CB LEU A 207 68. 962 57. ,640 11. .355 1. 00 58. .06 C

ATOM 1634 CG LEU A 207 68. 672 56. ,302 12. 049 1. 00 59. 65 C

ATOM 1635 CDl LEU A 207 61 . .255 56. .255 12. .537 1. 00 62. 24 C

ATOM 1636 CD2 LEU A 207 68. .926 55. ,145 11, ,144 1. 00 58. ,09 C

ATOM 1637 C LEU A 207 69, .223 59. ,250 13. ,380 1. 00 62. ,13 C

ATOM 1638 O LEU A 207 69. ,350 60. ,388 13, ,980 1. 00 64. ,45 O

ATOM 1639 OXT LEU A 207 69, ,775 58. .383 14. .067 1. 00 62. ,82 O

ATOM 1640 N HIS B 148 59. ,026 41. .578 -35. ,829 1. 00 91. ,87 N

ATOM 1641 CA HIS B 148 57. ,707 42. .121 -35. ,399 1. 00 92. ,51 C

ATOM 1642 CB HIS B 148 56. ,826 42. .652 -36. ,611 1. 00 93. ,52 C

ATOM 1643 CG HIS B 148 57. ,305 42. ,272 -38. ,016 1. 00 97. .91 C ATOM 1644 ND1 HIS B 148 56.836 42.910 -39.156 1.00100.37 N

ATOM 1645 CE1 HIS B 148 57 .397 42 .376 -40 .233 1 .00102 .09 C

ATOM 1646 NE2 HIS B 148 58 .199 41 .397 -39 .844 1 .00100 .74 N

ATOM 1647 CD2 HIS B 148 58 .159 41 .305 -38 .466 1 .00100 .06 C

ATOM 1648 C HIS B 148 56 .992 41 .058 -34 .490 1 .00 91 .29 C

ATOM 1649 O HIS B 148 56 .958 41 .165 -33 .233 1 .00 90 .45 0

ATOM 1650 N LYS B 149 56 .450 40 .043 -35 .181 1 .00 89 .93 N

ATOM 1651 CA LYS B 149 55 .880 38 .765 -34 .675 1 .00 87 .74 C

ATOM 1652 CB LYS B 149 55 .897 37 .695 -35 .829 1 .00 88 .53 C

ATOM 1653 CG LYS B 149 57 .239 37 .625 -36 .687 1 .00 90 .03 C

ATOM 1654 CD LYS B 149 57 .241 36 .539 -37 .812 1 .00 92 .02 C

ATOM 1655 CE LYS B 149 58 .683 36 .046 -38 .126 1 .00 93 .89 c

ATOM 1656 NZ LYS B 149 59 .599 37 .119 -38 .677 1 .00 92 .96 N

ATOM 1657 C LYS B 149 56 .410 38 .143 -33 .343 1 .00 85 .14 C

ATOM 1658 O LYS B 149 55 .630 38 .011 -32 .387 1 .00 85 .44 0

ATOM 1659 N THR B 150 57 .692 37 .741 -33 .294 1 .00 81 .04 N

ATOM 1660 CA THR B 150 58 .244 37 .025 -32 .127 1 .00 76 .85 C

ATOM 1661 CB THR B 150 58 .868 35 .586 -32 .484 1 .00 77 .51 C

ATOM 1662 OG1 THR B 150 60 .185 35 .727 -33 .063 1 .00 72 .31 0

ATOM 1663 CG2 THR B 150 58 .014 34 .785 -33 .505 1 .00 78 .13 C

ATOM 1664 C THR B 150 59 .243 37 .776 -31 .253 1 .00 74 .14 C

ATOM 1665 O THR B 150 59 .644 37 .253 -30 .186 1 .00 73 .26 O

ATOM 1666 N PHE B 151 59 .681 38 .955 -31 .681 1 .00 70 .97 N

ATOM 1667 CA PHE B 151 60 .229 39 .926 -30 .₇04 1 .00 70 .05 C

ATOM 1668 CB PHE B 151 60 .575 41 .258 -31 .382 1 .00 69 .97 C

ATOM 1669 CG PHE B 151 61 .171 42 .271 -30 .449 1 .00 68 .24 c

ATOM 1670 CDl PHE B 151 62 .535 42 .337 -30 .252 1, .00 69 .76 c

ATOM 1671 CE1 PHE B 151 63 .098 43 .269 -29 .376 1, .00 67 .55 c

ATOM 1672 CZ PHE B 151 62 .266 44 .140 -28 .703 1, .00 66 .65 c

ATOM 1673 CE2 PHE B 151 60, .910 44 .075 -28 .894 1, .00 65 .41 c

ATOM 1674 CD2 PHE B 151 60, .361 43, .149 -29 . 45 1, .00 68, .05 c

ATOM 1675 C PHE B 151 59 .240 40 .154 -29 .477 1 .00 69 .00 c

ATOM 1676 O PHE B 151 59 .603 40 .065 -28 .302 1, .00 67 .08 0

ATOM 1677 N VAL B 152 57 .994 40 .390 -29 .818 1, .00 68 .78 N

ATOM 1678 CA VAL B 152 56 .903 40 .500 -28 .894 1, .00 71 .08 C

ATOM 1679 CB VAL B 152 55 .630 40 .883 -29 .715 1, .00 70 .64 c

ATOM 1680 CGI VAL B 152 54 .372 40, .591 -28 .969 1. .00 71 .15 c

ATOM 1681 CG2 VAL B 152 55, .707 42, .363 -30 .156 1, .00 71, .75 c

ATOM 1682 C VAL B 152 56, .699 39, .241 -28 .033 1. .00 71, .74 c

ATOM 1683 0 VAL B 152 56, .612 39, .320 -26 .798 1. .00 72, .05 0

ATOM 1684 N GLU B 153 56, .615 38, .089 -28 .691 1. .00 73, .10 N

ATOM 1685 CA GLU B 153 56, .518 36. .774 -28 .027 1. ,00 74, .09 C

ATOM 1686 CB GLU B 153 56, .476 35. .661 -29, .068 1. ,00 75. ,16 C

ATOM 1687 CG GLU B 153 55, .099 35. .033 -29, .278 1. ,00 82. .55 c

ATOM 1688 CD GLU B 153 54. ,448 35. .407 -30, .620 1. ,00 90. ,17 c

ATOM 1689 OEl GLU B 153 55. ,069 35. .155 -31, .701 1. .00 91. ,61 0

ATOM 1690 OE2 GLU B 153 53. .300 35. ,954 -30, .584 1. 00 92. ,45 0

ATOM 1691 C GLU B 153 57. ,656 36. .507 -27, .035 1. 00 71. ,98 c

ATOM 1692 O GLU B 153 57. .421 35. ,968 -25, .992 1. 00 73. ,38 o

ATOM 1693 N LYS B 154 58. ,876 36. ,905 -27. .355 1. 00 69. ,65 N

ATOM 1694 CA LYS B 154 60. ,009 36. ,840 -26, .423 1. 00 67. ,44 C

ATOM 1695 CB LYS B 154 61. ,238 37. ,313 -27. .186 1. 00 67. ,41 C

ATOM 1696 CG LYS B 154 62. ,567 36. ,952 -26. ,588 1. 00 71. 27 C

ATOM 1697 CD LYS B 154 63. ,448 36. 163 -27. ,588 1. 00 78. 11 C

ATOM 1698 CE LYS B 154 64. ,389 35. 144 -26. ,854 1. 00 84. 36 c

ATOM 1699 NZ LYS B 154 65. ,380 35. 732 -25. ,847 1. 00 83. 97 N

ATOM 1700 C LYS B 154 59. ,908 37. 760 -25. ,183 1. 00 66. 00 C

ATOM 1701 0 LYS B 154 60. .363 37. .420 -24, .078 1. 00 64. ,44 O

ATOM 1702 N TYR B 155 59. .379 38. ,967 -25, .395 1. 00 63. ,61 N

ATOM 1703 CA TYR B 155 59. .736 40. ,071 -24, .542 1. 00 60. ,84 C

ATOM 1704 CB TYR B 155 60, ,530 41. ,057 -25, .356 1. 00 60. ,95 C

ATOM 1705 CG TYR B 155 61. ,943 40. ,655 -25. ,656 1. 00 65. 39 C

ATOM 1706 CDl TYR B 155 62. ,774 40. ,089 -24. ,672 1. 00 69. 29 C

ATOM 1707 CE1 TYR B 155 64. .110 39. ,741 -24. ,966 1. 00 70. 22 C

ATOM 1708 CZ TYR B 155 64. ,575 39. 954 -26, ,294 1. 00 71. 92 C

ATOM 1709 OH TYR B 155 65, ,863 39. .668 -26. ,669 1. 00 71. 46 0

ATOM 1710 CE2 TYR B 155 63. ,752 40. .520 -27. ,261 1. 00 67. 70 C

ATOM 1711 CD2 TYR B 155 62. .469 40. 862 -26. ,940 1. 00 66. 31 C

ATOM 1712 C TYR B 155 58. ,508 40. 750 -23. ,925 1. 00 58. 17 c

ATOM 1713 0 TYR B 155 58. ,617 41. 783 -23. ,274 1. 00 57. 34 o

ATOM 1714 N GLU B 156 57. ,361 40. 151 -24. ,181 1. 00 55. 17 N

ATOM 1715 CA GLU B 156 56. ,089 40. 646 -23. ,777 1. 00 53. 90 C

ATOM 1716 CB GLU B 156 55. ,084 39. 552 -23. 901 1. 00 52. 03 C

ATOM 1717 CG GLU B 156 53. ,685 40. 059 -23. 860 1. 00 57. 93 C

ATOM 1718 CD GLU B 156 52. 704 38. 973 -23. 588 1. 00 63. 91 C

ATOM 1719 OEl GLU B 156 51. 877 39. 106 -22. 633 1. 00 69. 08 0

ATOM 1720 OE2 GLU B 156 52. 785 37. 984 -24. 321 1. 00 65. 56 0 ATOM 1721 C GLU B 156 56.055 41.229 -22.342 1.00 53.79 c

ATOM 1722 O GLU B 156 55 .581 42 .358 -22 .139 1 .00 52 .95 O

ATOM 1723 N LYS B 157 56 .584 40 .478 -21 .378 1 .00 52 .20 N

ATOM 1724 CA LYS B 157 56 .469 40 .809 -19 .992 1 .00 52 .25 c

ATOM 1725 CB LYS B 157 56 .683 39 .580 -19 .091 1 .00 52 .85 c

ATOM 1726 CG LYS B 157 55 .579 38 .528 -19 .509 1 .00 60 .52 c

ATOM 1727 CD LYS B 157 54 .740 37 .936 -18 .378 1 .00 67 .27 c

ATOM 1728 CE LYS B 157 54 .920 36 .397 -18 .331 1 .00 69 .76 c

ATOM 1729 NZ LYS B 157 53 .919 35 .710 -17 .445 1 .00 69 .54 N

ATOM 1730 C LYS B 157 57 .335 42 .015 -19 .704 1 .00 49 .47 C

ATOM 1731 O LYS B 157 56 .953 42 .874 -18 .937 1 .00 47 .37 O

ATOM 1732 N GLN B 158 58 .407 42 .137 -20 .431 1 .00 45 .71 N

ATOM 1733 CA GLN B 158 59 .340 43 .190 -20 .159 1 .00 46 .48 C

ATOM 1734 CB GLN B 158 60 .686 42 .843 -20 .835 1 .00 46 .74 C

ATOM 1735 CG GLN B 158 61 .613 41 .706 -20 .225 1 .00 52 .54 C

ATOM 1736 CD GLN B 158 63 .022 41 .809 -20 .889 1 .00 64 .10 C

ATOM 1737 OEl GLN B 158 63 .142 41 .649 -22 .121 1 .00 63 .48 O

ATOM 1738 NE2 GLN B 158 64 .051 42 .220 -20 .103 1 .00 66 .21 N

ATOM 1739 C GLN B 158 58 .847 44 .538 -20 .756 1 .00 45 .21 C

ATOM 1740 O GLN B 158 59 .182 45 .624 -20 .251 1 .00 44 .41 O

ATOM 1741 N ILE B 159 58 ^'.167 44 .441 -21 .897 1 .00 43 .00 N

ATOM 1742 CA ILE B 159 57 .590 45 .590 -22 .569 1 .00 42 .52 C

ATOM 1743 CB ILE B 159 56 .999 45 .207 -23 .949 1 .00 41 .92 C

ATOM 1744 CGI ILE B 159 58 .117 44 .798 -24 .988 1 .00 46 .57 C

ATOM 1745 CDl ILE B 159 57 .534 43 .821 -26 .077 1 .00 40 .65 C

ATOM 1746 CG2 ILE B 159 56 .349 46 .352 -24 .541 1 .00 41 .72 C

ATOM 1747 C ILE B 159 56 .440 46 .090 -21 .633 1 .00 40 .20 C

ATOM 1748 O ILE B 159 56 .340 47 .226 -21 .381 1 .00 37 .39 O

ATOM 1749 N LYS B 160 55 .584 45 .166 -21 .207 1 .00 38 .31 N

ATOM 1750 CA LYS B 160 54 .513 45 .442 -20 .310 1 .00 37 .09 C

ATOM 1751 CB LYS B 160 53 .688 44 .242 -20 .041 1 .00 34 .83 C

ATOM 1752 CG LYS B 160 52 .795 43 .976 -21 .198 1 .00 27 .77 C

ATOM 1753 CD LYS B 160 51 .848 42 .695 -20, .899 1 .00 31 .63 C

ATOM 1754 CE LYS B 160 50 .849 42, .529 -22, .084 1 .00 30 .76 C

ATOM 1755 NZ LYS B 160 49 .825 41, .515 -21, .953 1, .00 40 .85 N

ATOM 1756 C LYS B 160 55 .048 46, .096 -19, .048 1, .00 38 .77 C

ATOM 1757 O LYS B 160 54 .573 47, .141 -18, .676 1, .00 40 .07 O

ATOM 1758 N HIS B 161 56 .136 45, .580 -18. ,499 1, .00 38, .15 N

ATOM 1759 CA HIS B 161 56, .658 46, .103 -17. ,289 1, .00 35, .34 C

ATOM 1760 CB HIS B 161 57, .853 45, ,253 -16. ,866 1. .00 37, .86 C

ATOM 1761 CG HIS B 161 58, .563 45. ,775 -15. ,666 1, .00 34, .19 C

ATOM 1762 ND1 HIS B 161 58, .131 45, .497 -14. ,389 1, .00 30, .13 N

ATOM 1763 CE1 HIS B 161 58, .941 46. .075 -13. .504 1. .00 28, .72 C

ATOM 1764 NE2 HIS B 161 59, .866 46. ,742 -14. ,173 1. .00 35. .40 N

ATOM 1765 CD2 HIS B 161 59. .650 46. ,568 -15. ,539 1. .00 31, .21 C

ATOM 1766 C HIS B 161 57. .089 47. ,493 -17. .494 1. ,00 34. .74 C

ATOM 1767 O HIS B 161 56, .856 48. ,277 -16. .636 1. ,00 35. .33 O

ATOM 1768 N PHE B 162 57, .816 47. ,794 -18. .587 1. ,00 34. ,70 N

ATOM 1769 CA PHE B 162 58. .317 49. ,137 -18. ,926 1. ,00 31. ,09 C

ATOM 1770 CB PHE B 162 59. .094 49. ,097 -20. ,251 1. ,00 29. ,96 C

ATOM 1771 CG PHE B 162 59. ,415 50. ,481 -20. ,778 1. ,00 30. .83 C

ATOM 1772 CDl PHE B 162 60, ,400 51. ,244 -20. ,186 1. ,00 28. ,53 C

ATOM 1773 CE1 PHE B 162 60, .643 52. ,573 -20. ,572 1. .00 24. .49 C

ATOM 1774 CZ PHE B 162 59, .823 53. ,169 -21. ,509 1. .00 29. .46 C

ATOM 1775 CE2 PHE B 162 58, .773 52. .459 -22. ,078 1. .00 33. ,85 C

ATOM 1776 CD2 PHE B 162 58. .580 51. .083 -21. ,720 1. ,00 36. ,27 C

ATOM 1777 C PHE B 162 57. .066 50. ,081 -19. ,080 1. ,00 32. ,62 C

ATOM 1778 O PHE B 162 57. ,118 51. ,275 -18. ,735 1. ,00 32. ,67 O

ATOM 1779 N GLY B 163 55, ,994 49. ,529 -19. ,660 1. ,00 32. ,17 N

ATOM 1780 CA GLY B 163 54. ,713 50. ,198 -19. ,889 1. ,00 32. ,63 C

ATOM 1781 C GLY B 163 54. ,159 50. ,676 -18. ,537 1. ,00 32. ,71 C

ATOM 1782 O GLY B 163 53. ,483 51. ,709 -18. ,460 1. ,00 33. 87 O

ATOM 1783 N MET B 164 54. ,451 49. ,956 -17. 473 1. 00 30. ,61 N

ATOM 1784 CA MET B 164 53. ,842 50. ,266 -16. 194 1. 00 29. ,79 C

ATOM 1785 CB MET B 164 53. ,326 49. 008 -15. 535 1. 00 29. 61 C

ATOM 1786 CG MET B 164 52. ,067 48. ,375 -16. .354 1. 00 27. 50 C

ATOM 1787 SD MET B 164 51. ,552 46. ,871 -15. 493 1. 00 37. 56 S

ATOM 1788 CE MET B 164 52. ,918 45. ,500 -16. 097 1. 00 33. 12 C

ATOM 1789 C MET B 164 54. ,695 51. ,156 -15. 296 1. 00 28. ,86 C

ATOM 1790 O MET B 164 54. ,274 51. ,613 -14. 273 1. 00 31. 02 O

ATOM 1791 N LEU B 165 55. ,861 51. ,513 -15, 728 1. 00 28. 66 N

ATOM 1792 CA LEU B 165 56. .731 52, ,346 -14. 891 1. 00 29. 71 C

ATOM 1793 CB LEU B 165 58. ,243 52. ,208 -15. 301 1. 00 28. 66 C

ATOM 1794 CG LEU B 165 58. ,865 50. ,820 -15. 106 1. 00 29. 71 C

ATOM 1795 CDl LEU B 165 60. ,287 50. 770 -15. 716 1. 00 24. 64 C

ATOM 1796 CD2 LEU B 165 58. ,898 50. ,460 -13. 545 1. 00 30. 97 C

ATOM 1797 C LEU B 165 56. ,365 53. 777 -15. 139 1. 00 28. 59 C ATOM 1798 O LEU B 165 55.572 54.075 -16.022 1.00 29.74 0

ATOM 1799 N ARG B 166 57 .019 54 .680 -14 .452 1 .00 28 .75 N

ATOM 1800 CA ARG B 166 56 .665 56 .047 -14 .595 1 .00 27 .46 C

ATOM 1801 CB ARG B 166 55 .447 56 .389 -13 .633 1 .00 29 .40 C

ATOM 1802 CG ARG B 166 55 .156 57 .958 -13 .569 1 .00 31 .50 C

ATOM 1803 CD ARG B 166 54 .588 58 .156 -14 .813 1 .00 43 .91 C

ATOM 1804 NE ARG B 166 53 .608 59 .145 -14 .632 1 .00 58 .60 N

ATOM 1805 CZ ARG B 166 52 .330 59 .092 -14 .907 1 .00 49 .87 C

ATOM 1806 NH1 ARG B 166 51 .675 58 .035 -15 .379 1 .00 37 .51 N

ATOM 1807 NH2 ARG B 166 51 .752 60 .214 -14 .662 1 .00 45 .65 N

ATOM 1808 C ARG B 166 57 .799 56 .879 -14 .189 1 .00 27 .06 C

ATOM 1809 O ARG B 166 58 .048 57 .926 -14 .838 1 .00 27 .96 O

ATOM 1810 N ARG B 167 58 .431 56 .600 -13 .053 1 .00 29 .26 N

ATOM 1811 CA ARG B 167 59 .538 57 .577 -12 .623 1 .00 34 .01 C

ATOM 1812 CB ARG B 167 60 .143 57 .217 -11 .230 1 .00 35 .78 C

ATOM 1813 CG ARG B 167 59 .097 56 .902 -10 .144 1 .00 41 .53 C

ATOM 1814 CD ARG B 167 59 .649 56 .594 -8 .656 1 .00 43 .93 C

ATOM 1815 NE ARG B 167 59 .015 57 .671 -7 .879 1 .00 51 .35 N

ATOM 1816 CZ ARG B 167 58 .316 57 .600 -6 .754 1 .00 46 .80 C

ATOM 1817 NH1 ARG B 167 58 .167 56 .525 -5 .985 1 .00 45 .58 N

ATOM 1818 NH2 ARG B 167 57 .856 58 .712 -6 .327 1 .00 52 .56 N

ATOM 1819 C ARG B 167 60 .709 57 .573 -13 .654 1 .00 33 .91 C

ATOM 1820 O ARG B 167 61 .014 56 .526 -14 .235 1 .00 34 .03 O

ATOM 1821 N TRP B 168 61 .288 58 .720 -13 .944 1 .00 36, .12 N

ATOM 1822 CA TRP B 168 62 .287 58, .768 -15 .005 1 .00 38 .79 C

ATOM 1823 CB TRP B 168 62 .776 60, .180 -15 .316 1 .00 39 .11 C

ATOM 1824 CG TRP B 168 61 .685 61, .239 -15 .483 1 .00 40 .84 C

ATOM 1825 CDl TRP B 168 61 .570 62, .380 -14 .784 1 .00 40 .15 C

ATOM 1826 NE1 TRP B 168 60 .542 63 .126 -15 .278 1 .00 39 .41 N

ATOM 1827 CE2 TRP B 168 59 .985 62 .486 -16 .329 1 .00 36 .86 C

ATOM 1828 CD2 TRP B 168 60 .714 61 .311 -16 .529 1 .00 38 .27 C

ATOM 1829 CE3 TRP B 168 60, .360 60, .463 -17, .595 1. .00 35, .90 C

ATOM 1830 CZ3 TRP B 168 59, .300 60, .841 -18, .398 1, .00 37, .29 C

ATOM 1831 CH2 TRP B 168 58, .570 62. .028 -18 .144 1, .00 41, .22 C

ATOM 1832 CZ2 TRP B 168 58, .921 62, .876 -17, .141 1, .00 38, .59 C

ATOM 1833 C TRP B 168 63 .536 57. ,938 -14 .721 1, .00 39, .55 C

ATOM 1834 O TRP B 168 63, .980 57, ,233 -15, .604 1, .00 40, .37 O

ATOM 1835 N ASP B 169 64, .078 57, .989 -13, .519 1, .00 41, .00 N

ATOM 1836 CA ASP B 169 65, .200 57. .092 -13, .137 1, .00 43, .31 C

ATOM 1837 CB ASP B 169 65, .748 57, .385 -11, .734 1, .00 43. .86 C

ATOM 1838 CG ASP B 169 66, .380 58. ,782 -11. ,651 1. ,00 50. ,37 C

ATOM 1839 OD1 ASP B 169 66, .762 59. ,289 -12. ,725 1, ,00 52. ,11 O

ATOM 1840 OD2 ASP B 169 66, .502 59. ,484 -10. ,580 1, .00 57] !63 0

ATOM 1841 C ASP B 169 64, .873 55. .656 -13. ,271 1. .00 43. .02 c

ATOM 1842 O ASP B 169 65, .730 54. .859 -13. ,694 1. ,00 44. .78 0

ATOM 1843 N ASP B 170 63, .632 55. .271 -13. ,012 1, .00 42. ,56 N

ATOM 1844 CA ASP B 170 63, .363 53. ,823 -13, ,141 1. .00 41. ,79 C

ATOM 1845 CB ASP B 170 62, .219 53. .328 -12, ,247 1, ,00 40. ,54 C

ATOM 1846 CG ASP B 170 62. .367 53. 814 -10. ,837 1. ,00 44. 80 c

ATOM 1847 OD1 ASP B 170 63 , ,524 53. ,984 -10. 368 1. ,00 53. 01 0

ATOM 1848 OD2 ASP B 170 61. .406 54. ,103 -10. 118 1. ,00 49. 03 o

ATOM 1849 C ASP B 170 63, .215 53. ,412 -14. ,566 1. ,00 40. 57 c

ATOM 1850 O ASP B 170 63. .584 52. ,323 -14. .917 1. ,00 39. ,71 o

ATOM 1851 N SER B 171 62, .672 54. 305 -15. .368 1. ,00 38. 94 N

ATOM 1852 CA SER B 171 62. .452 54. ,012 -16. .776 1. ,00 39. 89 C

ATOM 1853 CB SER B 171 61, .640 55. ,164 -17. ,455 1. ,00 37. 38 C

ATOM 1854 OG SER B 171 60, .213 54. ,930 -17. .340 1. ,00 45. ,03 O

ATOM 1855 C SER B 171 63. ,863 53. 899 -17. 445 1. 00 39. 14 C

ATOM 1856 O SER B 171 64. .098 52. 896 -18. 112 1. 00 37. 96 0

ATOM 1857 N GLN B 172 64. .732 54. 926 -17. 278 1. 00 39, 11 N

ATOM 1858 CA GLN B 172 66, .189 54. ,896 -17. 648 1. 00 42. 99 c

ATOM 1859 CB GLN B 172 66. .988 55. ,162 -17. ,226 1. ,00 42. 58 c

ATOM 1860 CG GLN B 172 68, .328 56. ,376 -17. 980 1. ,00 44. 74 c

ATOM 1861 CD GLN B 172 69, .002 57. ,636 -17. ,547 1. ,00 51. ,57 c

ATOM 1862 OEl GLN B 172 69, .107 57. ,869 -16. .379 1. ,00 58. ,07 0

ATOM 1863 NE2 GLN B 172 69, .419 58. ,485 -18. ,479 1. ,00 54. ,95 N

ATOM 1864 C GLN B 172 66. ,849 53. 572 -17. 196 1. 00 43. 43 C

ATOM 1865 O GLN B 172 67. ,243 52. 782 -18. 021 1. 00 44. 29 O

ATOM 1866 N LYS B 173 66. ,770 53. 240 -15. 920 1. 00 45. 39 N

ATOM 1867 CA LYS B 173 67. ,492 52. 083 -15. 438 1. ,00 46. ,52 C

ATOM 1868 CB LYS B 173 67. .392 51. ,961 -13. ,919 1. ,00 46. ,78 C

ATOM 1869 CG LYS B 173 68, .250 50. ,788 -13. .385 1. ,00 51. ,25 C

ATOM 1870 CD LYS B 173 68, ,019 50. ,476 -11. 901 1. ,00 57. ,05 C

ATOM 1871 CE LYS B 173 69, .005 49. ,327 -11. .435 1. ,00 64. ,05 C

ATOM 1872 NZ LYS B 173 69, .609 48. ,517 -12. ,590 1. ,00 61. ,70 N

ATOM 1873 C LYS B 173 67. .024 50. 831 -16. 117 1. 00 47. 39 C

ATOM 1874 O LYS B 173 67. ,843 49. 943 -16. 519 1. 00 49. 74 O ATOM 1875 N TYR B 174 65.716 50.709 -16.252 1.00 45.31 N

ATOM 1876 CA TYR B 174 65 .212 49 .480 -16 .804 1 .00 43 .14 C

ATOM 1877 CB TYR B 174 63 .711 49 .424 -16 .672 1 .00 40 .77 C

ATOM 1878 CG TYR B 174 63 .171 48 .089 -16 .994 1 .00 36 .09 c

ATOM 1879 CDl TYR B 174 63 .358 47 .030 -16 .095 1 .00 31 .75 c

ATOM 1880 CE1 TYR B 174 62 .823 45 .709 -16 .397 1 .00 29 .78 c

ATOM 1881 CZ TYR B 174 62 .109 45 .553 -17 .622 1 .00 33 .57 c

ATOM 1882 OH TYR B 174 61 .493 44 .363 -17 .918 1 .00 40 .95 0

ATOM 1883 CE2 TYR B 174 61 .841 46 .658 -18 .481 1 .00 31 .48 c

ATOM 1884 CD2 TYR B 174 62 .419 47 .885 -18 .187 1 .00 28 .82 c

ATOM 1885 C TYR B 174 65 .574 49 .304 -18 .286 1 .00 44 .84 c

ATOM 1886 O TYR B 174 65 .760 48 .169 -18 .726 1 .00 44 .59 o

ATOM 1887 N LEU B 175 65 .553 50 .386 -19 .064 1 .00 45 .93 N

ATOM 1888 CA LEU B 175 65 .933 50 .321 -20 .458 1 .00 47 .27 C

ATOM 1889 CB LEU B 175 65 .638 51 .654 -21 .149 1 .00 46 .57 c

ATOM 1890 CG LEU B 175 64 .139 51 .963 -21 .416 1 .00 44 .11 c

ATOM 1891 CDl LEU B 175 63 .930 53 .206 -22 .257 1 .00 37 .37 c

ATOM 1892 CD2 LEU B 175 63 .516 50 .727 -22 .006 1 .00 43 .54 c

ATOM 1893 C LEU B 175 67 .472 50 .020 -20 .555 1 .00 49 .98 c

ATOM 1894 O LEU B 175 67 .874 49 .141 -21 .304 1 .00 50 .26 0

ATOM 1895 N SER B 176 68 .281 50 .744 -19 .785 1 .00 50 .94 N

ATOM 1896 CA SER B 176 69 .668 50 .398 -19 .568 1 .00 54 .01 C

ATOM 1897 CB SER B 176 70 .249 51 .162 -18 .400 1 .00 54 .29 C

ATOM 1898 OG SER B 176 70 .618 52 .481 -18 .810 1 .00 59 .85 0

ATOM 1899 C SER B 176 69 .952 48 .873 -19 .383 1 .00 54 .54 c

ATOM 1900 O SER B 176 70 .808 48 .326 -20 .130 1 .00 57 .18 o

ATOM 1901 N ASP B 177 69 .260 48 .210 -18 .456 1 .00 51 .23 N

ATOM 1902 CA ASP B 177 69 .422 46 .787 -18 .258 1 .00 50 .21 C

ATOM 1903 CB ASP B 177 68, .750 46, .352 -16 .953 1 .00 49 .00 C

ATOM 1904 CG ASP B 177 69, .358 47, .002 -15 .769 1 .00 54, .47 C

ATOM 1905 OD1 ASP B 177 70, .351 47, .737 -15 .951 1, .00 59 .82 0

ATOM 1906 OD2 ASP B 177 68, .909 46. .861 -14 .605 1. .00 57. .37 o

ATOM 1907 C ASP B 177 68 .793 45 .953 -19 .344 1 .00 48 .39 c

ATOM 1908 O ASP B 177 68, .740 44, .698 -19 .253 1 .00 46 .99 0

ATOM 1909 N ASN B 178 68, .157 46 .603 -20 .284 1. .00 46 .30 N

ATOM 1910 CA ASN B 178 67, .490 45, .778 -21 .237 1, .00 47 .05 C

ATOM 1911 CB ASN B 178 66, .092 45, .297 -20 .811 1, .00 46, .91 C

ATOM 1912 CG ASN B 178 65, .987 44, .755 -19 .337 1, .00 50, .23 C

ATOM 1913 OD1 ASN B 178 65. .875 45, .550 -18 .321 1, .00 47, .10 O

ATOM 1914 ND2 ASN B 178 65, .845 43, .410 -19. .227 1, .00 46, .35 N

ATOM 1915 C ASN B 178 67. .432 46. .624 -22, .505 1, .00 48, .78 C

ATOM 1916 O ASN B 178 66. ,350 46, .840 -23, .067 1, ,00 48, .97 O

ATOM 1917 N VAL B 179 68. ,599 47, .106 -22, .982 1. .00 49, .34 N

ATOM 1918 CA VAL B 179 68. ,599 48. .051 -24, .067 1. .00 48. .93 C

ATOM 1919 CB VAL B 179 69. ,908 48. ,699 -24, .302 1. .00 SO, .24 C

ATOM 1920 CGI VAL B 179 69. ,700 50. .121 -24, .991 1. ,00 52. ,03 C

ATOM 1921 CG2 VAL B 179 70. ,583 48. ,912 -22, .969 1. ,00 51. ,67 C

ATOM 1922 C VAL B 179 67. ,967 47. ,588 -25, ,348 1. ,00 49. ,97 C

ATOM 1923 O VAL B 179 67. ,736 48. ,407 -26. .223 1. ,00 50. ,59 O

ATOM 1924 N HIS B 180 67. ,644 46. ,312 -25. .469 1. ,00 49. ,99 N

ATOM 1925 CA HIS B 180 66. .909 45. ,852 -26. .653 1. ,00 51. ,47 C

ATOM 1926 CB HIS B 180 66. 985 44. ,312 -26. .744 1. ,00 51. ,31 C

ATOM 1927 CG HIS B 180 66. 526 43. 610 -25. ,499 1. ,00 51. 66 c

ATOM 1928 ND1 HIS B 180 67. 317 43. 505 -24. .367 1. 00 51. 63 N

ATOM 1929 CE1 HIS B 180 66. 658 42. 845 -23. ,422 1. 00 SO. 65 C

ATOM 1930 NE2 HIS B 180 65. 463 42. 506 -23. ,902 1. 00 51. 02 N

ATOM 1931 CD2 HIS B 180 65. 342 43. 006 -25. ,189 1. 00 52. 24 C

ATOM 1932 C HIS B 180 65. 412 46. 252 -26. ,677 1. 00 52. 27 C

ATOM 1933 O HIS B 180 64. .699 46. ,112 -27. .732 1. ,00 54. .09 O

ATOM 1934 N LEU B 181 64. .885 46. ,648 -25, .512 1. ,00 51. ,17 N

ATOM 1935 CA LEU B 181 63. ,472 47. ,131 -25. .447 1. ,00 49. ,59 C

ATOM 1936 CB LEU B 181 62. ,996 47. ,291 -24. ,007 1. ,00 47. ,64 C

ATOM 1937 CG LEU B 181 62. 830 45. 930 -23. ,343 1. 00 43. 54 C

ATOM 1938 CDl LEU B 181 62. 530 45. 995 -21. ,872 1. 00 37. 02 C

ATOM 1939 CD2 LEU B 181 61. 846 45. 019 -24. ,089 1. 00 40. 99 C

ATOM 1940 C LEU B 181 63. 278 48. 433 -26. ,255 1. 00 49. 69 C

ATOM 1941 O LEU B 181 62. 193 48. 678 -26. ,790 1. 00 51. 35 O

ATOM 1942 N VAL B 182 64. 361 49. 188 -26. ,405 1. 00 49. 18 N

ATOM 1943 CA VAL B 182 64. 372 50. 503 -27. ,009 1. 00 49. 51 C

ATOM 1944 CB VAL B 182 65. 675 51. 225 -26. ,597 1. 00 48. 85 C

ATOM 1945 CGI VAL B 182 65. 636 52. 691 -27. ,019 1. 00 49. 59 C

ATOM 1946 CG2 VAL B 182 65. 934 51. 084 -25. ,075 1. 00 45. 46 C

ATOM 1947 C VAL B 182 64. 283 50. 390 -28. .520 1. 00 51. 31 C

ATOM 1948 O VAL B 182 65. 300 50. 392 -29. 205 1. 00 52. 09 O

ATOM 1949 N CYS B 183 63. 082 50. 287 -29. 059 1. 00 52. 15 N

ATOM 1950 CA CYS B 183 62. 942 50. 102 -30. 504 1. 00 53. 48 C

ATOM 1951 CB CYS B 183 63. 430 48. 679 -30. 936 1. 00 51. 12 C ATOM 1952 SG CYS B 183 62.353 47.334 -30.294 1.00 56.51 s

ATOM 1953 C CYS B 183 61 .463 50 .276 -30 .905 1 .00 53 .65 c

ATOM 1954 O CYS B 183 60 .547 50 .145 -30 .057 1 .00 53 .95 o

ATOM 1955 N GLU B 184 61 .246 50 .478 -32 .204 1 .00 53 .20 N

ATOM 1956 CA GLU B 184 59 .946 50 .692 -32 .761 1 .00 53 .35 C

ATOM 1957 CB GLU B 184 60 .070 50 .824 -34 .287 1 .00 54 .59 C

ATOM 1958 CG GLU B 184 59 .796 52 .222 -34 .885 1 .00 63 .77 C

ATOM 1959 CD GLU B 184 58 .273 52 .518 -34 .962 1 .00 75 .56 C

ATOM 1960 OEl GLU B 184 57 .541 51 .940 -35 .857 1 .00 79 .95 O

ATOM 1961 OE2 GLU B 184 57 .784 53 .295 -34 .094 1 .00 77 .40 O

ATOM 1962 C GLU B 184 58 .970 49 .603 -32 .340 1 .00 52 .83 c

ATOM 1963 O GLU B 184 57 .793 49 .893 -32 .061 1 .00 52 .51 0

ATOM 1964 N GLU B 185 59 .423 48 .343 -32 .264 1 .00 52 .27 N

ATOM 1965 CA GLU B 185 58 .478 47 .259 -31 .990 1 .00 52 .26 C

ATOM 1966 CB GLU B 185 59 .007 45 .796 -32 .204 1 .00 53 .92 C

ATOM 1967 CG GLU B 185 59 .352 45 .375 -33 .656 1 .00 59 .41 C

ATOM 1968 CD GLU B 185 60 .316 46 .383 -34 .344 1 .00 69 .23 C

ATOM 1969 OEl GLU B 185 59 .949 46 .953 -35 .454 1 .00 73 .37 O

ATOM 1970 OE2 GLU B 185 61 .428 46 .654 -33 .766 1 .00 67 .29 O

ATOM 1971 C GLU B 185 57 .867 47 .392 -30 .594 1 .00 49 .60 C

ATOM 1972 O GLU B 185 56 .719 47, .047 -30 .436 1, .00 49 .40 o

ATOM 1973 N THR B 186 58 .643 47, .813 -29 .592 1 .00 47 .47 N

ATOM 1974 CA THR B 186 58 .020 48 .050 -28 .296 1 .00 46 .80 C

ATOM 1975 CB THR B 186 59 .002 47, .938 -27 .045 1, .00 48 .65 C

ATOM 1976 OG1 THR B 186 59 .085 49, .193 -26 .324 1 .00 53 .68 O

ATOM 1977 CG2 THR B 186 60 .400 47 .635 -27 .428 1 .00 43 .01 c

ATOM 1978 C THR B 186 57 .006 49 .242 -28 .336 1 .00 44 .57 c

ATOM 1979 O THR B 186 55 .836 49, ,022 -28, .022 1 .00 45 .85 0

ATOM 1980 N ALA B 187 57 .368 50 .409 -28 .876 1 .00 42 .66 N

ATOM 1981 CA ALA B 187 56 .349 51. .455 -29 .162 1, .00 42 .97 c

ATOM 1982 CB ALA B 187 56 .905 52 .652 -29 .980 1 .00 40 .23 c

ATOM 1983 C ALA B 187 55, .076 50, .924 -29 .768 1, .00 43 .00 c

ATOM 1984 O ALA B 187 53 .982 51, .106 -29, .176 1, .00 42 .55 0

ATOM 1985 N ASN B 188 55 .186 50, .203 -30, .914 1, .00 44 .10 N

ATOM 1986 CA ASN B 188 53, ,977 49, .655 -31, .570 1. .00 43. .48 C

ATOM 1987 CB ASN B 188 5 .232 49, .046 -33, .015 1. .00 46, .39 C

ATOM 1988 CG ASN B 188 54 ,980 50, .010 -33, .907 1. .00 49. .96 C

ATOM 1989 OD1 ASN B 188 55, .112 51. .186 -33, .559 1, .00 56 .73 O

ATOM 1990 ND2 ASN B 188 55, .520 49, .526 -35. .030 1. .00 55, .42 N

ATOM 1991 C ASN B 188 53, .195 48. .678 -30. .722 1, .00 40. .56 C

ATOM 1992 O ASN B 188 51, .968 48, ,681 -30, .793 1. .00 41. .01 O

ATOM 1993 N TYR B 189 53. .854 47. .839 -29. .933 1. .00 38. .69 N

ATOM 1994 CA TYR B 189 53, .085 46. ,862 -29. ,044 1. .00 38. ,20 C

ATOM 1995 CB TYR B 189 54, .116 45. .828 -28. ,463 1. .00 38. .26 C

ATOM 1996 CG TYR B 189 53, .464 44. .799 -27, .583 1. .00 42, .32 C

ATOM 1997 CDl TYR B 189 52 .767 43. .705 -28. .151 1. .00 50, .64 C

ATOM 1998 CE1 TYR B 189 52, .068 42. ,736 -27. .323 1. .00 51, ,28 C

ATOM 1999 CZ TYR B 189 52. ,076 42. .886 -25. .943 1. ,00 48. ,75 C

ATOM 2000 OH TYR B 189 51 .371 42. .015 -25. ,174 1. ,00 54, ,76 O

ATOM 2001 CE2 TYR B 189 52 .689 43. ,985 -25. .363 1. .00 48, .31 C

ATOM 2002 CD2 TYR B 189 53. .408 44. ,949 -26. ,213 1. ,00 42. ,41 C

ATOM 2003 C TYR B 189 52, .408 47. ,668 -27. ,868 1. ,00 37. .34 c

ATOM 2004 O TYR B 189 51, .227 47. ,494 -27. ,504 1. ,00 37. .43 O

ATOM 2005 N LEU B 190 53. ,185 48. 574 -27. ,249 1. ,00 37. .50 N

ATOM 2006 CA LEU B 190 52, .584 49. .505 -26. ,256 1. ,00 36. .03 C

ATOM 2007 CB LEU B 190 53, .630 50. .496 -25. ,722 1. 00 36. .78 C

ATOM 2008 CG LEU B 190 54, .731 49. ,867 -24. ,794 1, ,00 35, .58 C

ATOM 2009 CDl LEU B 190 55. .527 50. ,899 -24. .349 1. ,00 32. 77 C

ATOM 2010 CD2 LEU B 190 54, ,162 49. ,121 -23. ,609 1. 00 35. 07 C

ATOM 2011 C LEU B 190 51, .364 50. ,179 -26. .855 1. ,00 34. ,41 C

ATOM 2012 O LEU B 190 50. .332 50, .158 -26. .229 1. ,00 34. ,91 O

ATOM 2013 N VAL B 191 51. .391 50. ,675 -28. 093 1. 00 35. 24 N

ATOM 2014 CA VAL B 191 50. .161 51. 302 -28. 637 1. ,00 35. ,74 C

ATOM 2015 CB VAL B 191 50. ,380 51. ,921 -30. .027 1. ,00 37. ,90 C

ATOM 2016 CGI VAL B 191 49, .056 52. ,373 -30. ,678 1. ,00 36. ,53 C

ATOM 2017 CG2 VAL B 191 51. ,518 52. 962 -30. 032 1. .00 33. .68 C

ATOM 2018 C VAL B 191 48. .965 50. ,352 -28. ,677 1. ,00 37. 82 C

ATOM 2019 O VAL B 191 47, .830 50. .711 -28. ,248 1. 00 37. .50 O

ATOM 2020 N ILE B 192 49. .214 49. ,102 -29. 107 1. 00 39. .57 N

ATOM 2021 CA ILE B 192 48. .118 48. .061 -29. ,201 1. 00 40. 13 C

ATOM 2022 CB ILE B 192 48. .622 46. .760 -30. 023 1. 00 42. 04 C

ATOM 2023 CGI ILE B 192 49. .039 47. .116 -31. 480 1. 00 43. ,72 C

ATOM 2024 CDl ILE B 192 47. 988 48. 017 -32. 180 1. 00 47. 54 C

ATOM 2025 CG2 ILE B 192 47. .551 45. 666 -30. 039 1. 00 43. 74 C

ATOM 2026 C ILE B 192 47. ,637 47. 667 -27. 827 1. 00 38. ,08 C

ATOM 2027 O ILE B 192 46. ,417 47. 560 -27. ,532 1. ,00 38. ,90 O

ATOM 2028 N TRP B 193 48. ,592 47. 489 -26. 929 1. 00 35. 88 N ATOM 2029 CA TRP B 193 48.214 47.199 -25.517 1.00 34.73 c

ATOM 2030 CB TRP B 193 49 .542 46 .961 -24 .656 1 .00 35 .17 c

ATOM 2031 CG TRP B 193 49 .214 46 .376 -23 .325 1 .00 34 .62 c

ATOM 2032 CDl TRP B 193 48 .181 45 .514 -23 .032 1 .00 31 .90 c

ATOM 2033 NE1 TRP B 193 48 .193 45 .182 -21 .695 1 .00 38 .26 N

ATOM 2034 CE2 TRP B 193 49 .274 45 .839 -21 .105 1 .00 38 .05 C

ATOM 2035 CD2 TRP B 193 49 .935 46 .574 -22 .115 1 .00 30 .74 C

ATOM 2036 CE3 TRP B 193 51 .071 47 .300 -21 .779 1 .00 33 .83 C

ATOM 2037 CZ3 TRP B 193 51 .504 47 .327 -20 .416 1 .00 35 .27 C

ATOM 2038 CH2 TRP B 193 50 .796 46 .616 -19 .432 1 .00 34 .43 C

ATOM 2039 CZ2 TRP B 193 49 .715 45 .839 -19 .758 1 .00 34 .87 c

ATOM 2040 C TRP B 193 47 .349 48 .336 -24 .915 1 .00 33 .50 c

ATOM 2041 O TRP B 193 46 .299 48 .077 -24 .250 1 .00 35 .93 o

ATOM 2042 N CYS B 194 47 .688 49 .604 -25 .167 1 .00 32 .33 N

ATOM 2043 CA CYS B 194 46 .692 50 .688 -24 .707 1 .00 33 .28 C

ATOM 2044 CB CYS B 194 47 .126 52 .130 -25 .091 1 .00 34 .74 C

ATOM 2045 SG CYS B 194 48 .643 52 .671 -24 .222 1 .00 33 .35 S

ATOM 2046 C CYS B 194 45 .287 50 .538 -25 .203 1 .00 31 .68 C

ATOM 2047 O CYS B 194 44 .365 50 .708 -24 .450 1 .00 33 .19 O

ATOM 2048 N ILE B 195 45 .092 50 .294 -26 .494 1 .00 34 .27 N

ATOM 2049 CA ILE B 195 43 .709 49 .971 -27 .060 1 .00 34 .27 C

ATOM 2050 CB ILE B 195 43 .753 49 .766 -28 .609 1 .00 35 .91 C

ATOM 2051 CGI ILE B 195 44 .370 51 .025 -29 .247 1 .00 36 .28 C

ATOM 2052 CDl ILE B 195 45 .149 50 .702 -30 .556 1 .00 40 .85 C

ATOM 2053 CG2 ILE B 195 42 .311 49 .560 -29 .187 1 .00 36 .48 C

ATOM 2054 C ILE B 19S 43 .106 48 .786 -26 .416 1 .00 34 .82 c

ATOM 2055 0 ILE B 195 41 .940 48 .885 -25 .926 1 .00 37 .13 0

ATOM 2056 N ASP B 196 43 .852 47 .669 -26 .261 1 .00 34 .42 N

ATOM 2057 CA ASP B 196 43 .193 46 .541 -25 .493 1 .00 35 .59 c

ATOM 2058 CB ASP B 196 44 .078 45 .244 -25 .333 1 .00 35 .99 c

ATOM 2059 CG ASP B 196 44 .485 4 .661 -26 .668 1 .00 42 .69 c

ATOM 2060 OD1 ASP B 196 43 .679 44 .799 -27 .634 1 .00 52 .44 o

ATOM 2061 OD2 ASP B 196 45 .570 44 .083 -26 .886 1 .00 53 .01 o

ATOM 2062 C ASP B 196 42 .768 46 .943 -24 .107 1 .00 35 .31 c

ATOM 2063 O ASP B 196 41 .698 46 .617 -23 .679 1 .00 37 .17 0

ATOM 2064 N LEU B 197 43 .649 47 .591 -23 .346 1 .00 35 .91 N

ATOM 2065 CA LEU B 197 43, .234 48 .011 -21 .985 1 .00 33 .38 c

ATOM 2066 CB LEU B 197 44, .387 48, .783 -21, .304 1. .00 33. .38 c

ATOM 2067 CG LEU B 197 45 .636 47 .892 -21 .106 1 .00 31 .74 c

ATOM 2068 CDl LEU B 197 46, .850 48, .785 -20, .791 1, .00 32. .30 c

ATOM 2069 CD2 LEU B 197 45, .351 46 .848 -19 .988 1 .00 30, .38 c

ATOM 2070 C LEU B 197 42. .017 48, .885 -22, .014 1. .00 32, .12 c

ATOM 2071 O LEU B 197 41, .133 48, .734 -21, .201 1 .00 32, .82 0

ATOM 2072 N GLU B 198 42, .010 49. .903 -22, .858 1, .00 32. .59 N

ATOM 2073 CA GLU B 198 40, ,850 50. .806 -22, .871 1, .00 34, .52 C

ATOM 2074 CB GLU B 198 41. ,040 51. .931 -23, .926 1, .00 35. .21 C

ATOM 2075 CG GLU B 198 39. ,868 52. .923 -24, .028 1, .00 38. .57 C

ATOM 2076 CD GLU B 198 39. .756 53. .796 -22, .769 1, ,00 47. .60 c

ATOM 2077 OEl GLU B 198 40. ,760 53. ,778 -22. ,000 1. ,00 49. ,39 0

ATOM 2078 OE2 GLU B 198 38. ,714 54, ,501 -22. .529 1. ,00 46. .77 0

ATOM 2079 C GLU B 198 39. ,562 49. .948 -23. ,259 1. ,00 36. .52 c

ATOM 2080 O GLU B 198 38. ,515 50. .133 -22. ,670 1, ,00 34. ,44 0

ATOM 2081 N VAL B 199 39. ,662 49. .040 -24. ,252 1. ,00 38. ,56 N

ATOM 2082 CA VAL B 199 38. ,480 48, .147 -24, .584 1. ,00 42. ,80 C

ATOM 2083 CB VAL B 199 38. ,754 47. ,191 -25. .806 1. ,00 43. ,74 C

ATOM 2084 CGI VAL B 199 37. ,542 46. ,207 -26. ,011 1. ,00 41. ,52 C

ATOM 2085 CG2 VAL B 199 39. 130 48. ,026 -27. ,078 1. ,00 38. ,33 c

ATOM 2086 C VAL B 199 38. ,067 47. .262 -23. ,374 1. .00 44. ,58 c

ATOM 2087 O VAL B 199 36. 849 47. ,153 -23. ,060 1. ,00 45. ,03 0

ATOM 2088 N GLU B 200 39. 069 46. ,703 -22. 652 1. 00 45. 05 N

ATOM 2089 CA GLU B 200 38. ,757 45. ,992 -21. ,395 1. ,00 45. 95 C

ATOM 2090 CB GLU B 200 39. 932 45. .194 -20. 933 1. 00 46. 78 C

ATOM 2091 CG GLU B 200 40. 437 44. ,239 -22. ,003 1. ,00 54. 64 C

ATOM 2092 CD GLU B 200 41. 828 43. 648 -21. 709 1. 00 64. 47 C

ATOM 2093 OEl GLU B 200 42. 365 42. ,895 -22. .635 1. .00 69. ,26 o

ATOM 2094 OE2 GLU B 200 42. 355 43. ,898 -20. .569 1. 00 63. 75 o

ATOM 2095 C GLU B 200 38. 288 46. ,881 -20. .270 1. .00 45. .25 c

ATOM 2096 O GLU B 200 38. 035 46. ,419 -19. ,206 1. 00 46. 48 0

ATOM 2097 N GLU B 201 38. 194 48. ,183 -20. .453 1. 00 45. .56 N

ATOM 2098 CA GLU B 201 37. 768 49. ,065 -19. 356 1. 00 46. 07 C

ATOM 2099 CB GLU B 201 36. 413 48. 666 -18. 833 1. 00 45. 40 C

ATOM 2100 CG GLU B 201 35. 284 48. ,858 -19. ,825 1. 00 54. 79 C

ATOM 2101 CD GLU B 201 33. 928 48. 766 -19. 135 1. 00 62. 79 C

ATOM 2102 OEl GLU B 201 33. 685 47. ,733 -18. ,419 1. 00 64. 90 0

ATOM 2103 OE2 GLU B 201 33. 140 49. 737 -19. 261 1. 00 63. 55 0

ATOM 2104 C GLU B 201 38. 792 49. ,267 -18. 144 1. 00 44. 24 c

ATOM 2105 O GLU B 201 38. 388 49. 678 -16. 988 1. 00 44. 88 o ATOM 2106 N LYS B 202 40.036 48.958 -18.445 00 39.77 N

ATOM 2107 CA LYS B 202 41.206 49.324 -17.625 00 40.93 C

ATOM 2108 CB LYS B 202 42.288 48.233 -17.732 00 40.40 C

ATOM 2109 CG LYS B 202 41.682 46.880 -17.329 00 43.23 C

ATOM 2110 CD LYS B 202 42.770 45.842 -17.082 00 51.03 C

ATOM 2111 CE LYS B 202 42.155 44.434 -16.766 00 61.21 C

ATOM 2112 NZ LYS B 202 43.077 43.754 -15.710 00 68.56 N

ATOM 2113 C LYS B 202 41.748 50.667 -18.101 1.00 37.98 C

ATOM 2114 O LYS B 202 42.852 50.760 -18.621 1.00 37,05 O

ATOM 2115 N CYS B 203 40.891 51.672 -17.983 1.00 36.24 N

ATOM 2116 CA CYS B 203 41.138 53.040 -18.366 1.00 36.11 C

ATOM 2117 CB CYS B 203 39.787 53.849 -18.172 1.00 37.06 C

ATOM 2118 SG CYS B 203 38.548 52.993 -19.245 00 50.11 S

ATOM 2119 C CYS B 203 42.237 53.659 -17.521 00 33.58 C

ATOM 2120 O CYS B 203 43.080 54.331 -18.075 00 32.96 O

ATOM 2121 N ALA B 204 42.195 53.480 -16.184 00 31.63 N

ATOM 2122 CA ALA B 204 43.202 54.082 -15.295 00 29.98 C

ATOM 2123 CB ALA B 204 42.901 53.742 -13.788 00 25.87 C

ATOM 2124 C ALA B 204 44.587 53.468 -15.729 1.00 30.12 C

ATOM 2125 O ALA B 204 45.532 54.195 -15.946 00 30.66 O

ATOM 2126 N LEU B 205 44.719 52.145 -15.869 00 29.36 N

ATOM 2127 CA LEU B 205 46.034 51.621 -16.393 00 28.60 C

ATOM 2128 CB LEU B 205 46.043 50.068 -16.261 00 30.01 C

ATOM 2129 CG LEU B 205 47.329 49.253 -16.591 00 32.48 C

ATOM 2130 CDl LEU B 205 48.411 49.764 -15.667 1.00 27.18 C

ATOM 2131 CD2 LEU B 205 47.078 47.700 -16.477 1.00 24.99 C

ATOM 2132 C LEU B 205 46.403 52.067 -17.801 1.00 29.89 C

ATOM 2133 O LEU B 205 47.648 52.253 -18.227 1.00 30.39 O

ATOM 2134 N MET B 206 45.373 52.192 -18.655 30.10 N

ATOM 2135 CA MET B 206 45.742 52.711 -20.021 30.67 C

ATOM 2136 CB MET B 206 44.487 52.826 -20.966 32.37 C

ATOM 2137 CG MET B 206 44.856 53.249 -22.361 31.94 C

ATOM 2138 SD MET B 206 45.106 55.053 -22.543 35.46 S

ATOM 2139 CE MET B 206 43.487 55.761 -22.472 30.39 C

ATOM 2140 C MET B 206 46.495 54.030 -19.935 1.00 29.56 C

ATOM 2141 O MET B 206 47.475 54.294 -20.711 1.00 31.10 o

ATOM 2142 N GLU B 207 46.108 54.906 -18.999 1.00 29.80 N

ATOM 2143 CA GLU B 207 46.820 56.182 -19.018 1.00 29.44 C

ATOM 2144 CB GLU B 207 46.122 57.218 -18.139 1.00 30.78 C

ATOM 2145 CG GLU B 207 44.604 57.248 -18.390 1.00 38.61 C

ATOM 2146 CD GLU B 207 43.969 58.597 -18.066 1.00 49.58 C

ATOM 2147 OEl GLU B 207 44.636 59.672 -17.945 1.00 50.94 O

ATOM 2148 OE2 GLU B 207 42.753 58.571 -17.920 1.00 57.06 O

ATOM 2149 C GLU B 207 48.247 56.049 -18.572 1.00 28.35 c

ATOM 2150 O GLU B 207 49.055 56.784 -19.029 29.52 0

ATOM 2151 N GLN B 208 48.512 55.146 -17.643 25.93 N

ATOM 2152 CA GLN B 208 49.856 54.914 -17.146 27.50 C

ATOM 2153 CB GLN B 208 49.796 53.805 -16.030 25.96 C

ATOM 2154 CG GLN B 208 51.186 53.401 -15.520 26.14 C

ATOM 2155 CD GLN B 208 51.684 54.388 -14.457 30.40 C

ATOM 2156 OEl GLN B 208 51.136 55.543 -14.287 28.48 0

ATOM 2157 NE2 GLN B 208 52.667 53.972 -13.738 27.01 N

ATOM 2158 C GLN B 208 50.680 54.386 -18.312 1.00 27.56 C

ATOM 2159 O GLN B 208 51.786 54.865 -18.532 1.00 28.00 O

ATOM 2160 N VAL B 209 50.139 53.409 -19.049 1.00 28.40 N

ATOM 2161 CA VAL B 209 50.870 52.837 -20.282 1.00 29.47 C

ATOM 2162 CB VAL B 209 50.162 51.556 -20.858 1.00 29.22 C

ATOM 2163 CGI VAL B 209 51.073 50.865 -22.102 1.00 25.01 C

ATOM 2164 CG2 VAL B 209 49.962 50.499 -19.692 1.00 26.44 C

ATOM 2165 C VAL B 209 51.053 53.876 -21.426 1.00 29.57 C

ATOM 2166 O VAL B 209 52.116 54.019 -21.994 1.00 30.77 O

ATOM 2167 N ALA B 210 50.020 54.659 -21.694 29.10 N

ATOM 2168 CA ALA B 210 50.146 55.716 -22.694 27.25 C

ATOM 2169 CB ALA B 210 48.785 56.532 -22.715 24.11 c

ATOM 2170 C ALA B 210 51.355 56.617 -22.390 28.81 c

ATOM 2171 O ALA B 210 52.074 57.034 -23.304 28.91 0

ATOM 2172 N HIS B 211 51.564 56.977 -21.116 28.21 N

ATOM 2173 CA HIS B 211 52.656 57.896 -20.799 29.07 C

ATOM 2174 CB HIS B 211 52.642 58.093 -19.263 26.80 C

ATOM 2175 CG HIS B 211 53.792 58.905 -18.763 29.72 C

ATOM 2176 ND1 HIS B 211 55.017 58.342 -18.452 1.00 31.18 N

ATOM 2177 CE1 HIS B 211 55.850 59.287 -18.030 1.00 31.30 C

ATOM 2178 NE2 HIS B 211 55.212 60.445 -18.056 1.00 33.06 N

ATOM 2179 CD2 HIS B 211 53.909 60.229 -18.470 1.00 32.71 C

ATOM 2180 C HIS B 211 53.992 57.263 -21.260 1.00 29.50 C

ATOM 2181 O HIS B 211 54.883 57.926 -21.819 1.00 29.60 O

ATOM 2182 N GLN B 212 54.145 55.969 -20.983 1.00 30.84 N ATOM 2183 CA GLN B 212 55.431 55.264 -21.260 1.00 31.51 c

ATOM 2184 CB GLN B 212 55 .429 53 .940 -20 .495 1 .00 31 .89 c

ATOM 2185 CG GLN B 212 55 .532 54 .097 -18 .939 1 .00 26 .78 c

ATOM 2186 CD GLN B 212 56 .844 54 .699 -18 .617 1 .00 32 .40 c

ATOM 2187 OEl GLN B 212 56 .906 55 .959 -18 .487 1 .00 30 .80 0

ATOM 2188 NE2 GLN B 212 57 .974 53 .865 -18 .649 1 .00 30 .90 N

ATOM 2189 C GLN B 212 55 .516 55 .066 -22 .813 1 .00 32 .27 C

ATOM 2190 O GLN B 212 56 .598 55 .091 -23 .405 1 .00 31 .41 O

ATOM 2191 N THR B 213 54 .363 54 .971 -23 .487 1 .00 32 .71 N

ATOM 2192 CA THR B 213 54 .353 54 .949 -24 .959 1 .00 35 .04 C

ATOM 2193 CB THR B 213 52 .932 54 .754 -25 .513 1 .00 34 .27 C

ATOM 2194 OG1 THR B 213 52 .346 53 .557 -24 .955 1 .00 36 .80 O

ATOM 2195 CG2 THR B 213 52 .995 54 .387 -26 .963 1 .00 36 .34 C

ATOM 2196 C THR B 213 54 .900 56 .222 -25 .573 1 .00 35 .39 C

ATOM 2197 O THR B 213 55 .793 56 .203 -26 .387 1 .00 36 .70 O

ATOM 2198 N ILE B 214 54 .356 57 .342 -25 .191 1 .00 35 .23 N

ATOM 2199 CA ILE B 214 54 .890 58 .587 -25 .629 1 .00 36 .17 C

ATOM 2200 CB ILE B 214 54 .052 59 .776 -24 .985 1 .00 36 .97 C

ATOM 2201 CGI ILE B 214 53 .072 60 .250 -26 .027 1 .00 42 .24 C

ATOM 2202 CDl ILE B 214 52 .113 59 .282 -26 .159 1 .00 49 .83 C

ATOM 2203 CG2 ILE B 214 54 .960 60 .994 -24 .713 1 .00 37 .06 C

ATOM 2204 C ILE B 214 56 .319 58 .667 -25 .273 1 .00 34 .94 C

ATOM 2205 O ILE B 214 57 .077 59 .245 -26 .051 1 .00 38 .40 O

ATOM 2206 N VAL B 215 56 .742 58 .187 -24 .097 1 .00 35 .92 N

ATOM 2207 CA VAL B 215 58 .194 58 .298 -23 .757 1 .00 38 .23 C

ATOM 2208 CB VAL B 215 58 .547 57 .708 -22 .372 1 .00 38 .13 C

ATOM 2209 CGI VAL B 215 60 .051 57 .369 -22 .198 1 .00 38 .02 C

ATOM 2210 CG2 VAL B 215 58 .103 58 .689 -21 .247 1 .00 41 .34 C

ATOM 2211 C VAL B 215 59 .043 57 .573 -24 .890 1 .00 39 .10 C

ATOM 2212 O VAL B 215 59. .959 58 .132 -25 .444 1 .00 39. .68 O

ATOM 2213 N MET B 216 58 .703 56 .343 -25 .167 1 .00 39 .71 N

ATOM 2214 CA MET B 216 59 .349 55 .496 -26 .163 1 .00 42, .62 C

ATOM 2215 CB MET B 216 58. .705 54 .096 -26 .214 1, .00 41, .33 C

ATOM 2216 CG MET B 216 59, ,562 53 .046 -27, .074 1, .00 47. .27 C

ATOM 2217 SD MET B 216 61 .394 53 .147 -26 .791 1 .00 47. .12 S

ATOM 2218 CE MET B 216 61, .515 52 .229 -25 .097 1, .00 42, .59 C

ATOM 2219 C MET B 216 59, .276 56 .184 -27, .530 1. .00 44, .38 C

ATOM 2220 O MET B 216 60. .359 56. .372 -28. .185 1. .00 44. ,48 O

ATOM 2221 N GLN B 217 58. .069 56 .637 -27 .922 1, .00 43, .63 N

ATOM 2222 CA GLN B 217 57. .970 57, .410 -29, .186 1. .00 45. .22 C

ATOM 2223 CB GLN B 217 56. .557 57, .886 -29. .555 1. ,00 43. ,36 C

ATOM 2224 CG GLN B 217 55, .621 56 .723 -29 .757 1, .00 47. .85 C

ATOM 2225 CD GLN B 217 54, .168 57, .123 -29. .994 1. ,00 49. ,88 C

ATOM 2226 OEl GLN B 217 53. ,719 58, .183 -29, .533 1. ,00 53. ,66 O

ATOM 2227 NE2 GLN B 217 53. ,416 56. ,248 -30. .679 1. ,00 45. 10 N

ATOM 2228 C GLN B 217 58. ,945 58, .579 -29, .151 1. ,00 45. .40 C

ATOM 2229 O GLN B 217 59. ,664 58, .809 -30, .110 1. ,00 47. .02 O

ATOM 2230 N PHE B 218 59. 032 59. ,267 -28. ,029 1. 00 45. .20 N

ATOM 2231 CA PHE B 218 59. 995 60. ,372 -27. ,991 1. 00 45. 80 C

ATOM 2232 CB PHE B 218 59. ,747 61, .373 -26. ,818 1. .00 44. .80 C

ATOM 2233 CG PHE B 218 58. ,483 62. ,175 -26. ,978 1. .00 44. 88 c

ATOM 2234 CDl PHE B 218 57. 768 62. .149 -28. ,191 1. 00 40. 67 c

ATOM 2235 CE1 PHE B 218 56. 581 62. 866 -28. 337 1. 00 39. 93 c

ATOM 2236 CZ PHE B 218 56, ,123 63, .664 -27, .310 1. ,00 38. 88 c

ATOM 2237 CE2 PHE B 218 56. 845 63, ,741 -26. ,103 1. 00 42. 92 c

ATOM 2238 CD2 PHE B 218 58. 006 62. 973 -25, 933 1. 00 44. 44 c

ATOM 2239 C PHE B 218 61. 448 59. ,990 -28. .035 1. 00 44. 53 c

ATOM 2240 O PHE B 218 62. 270 60, ,809 -28. ,467 1. 00 41. 21 0

ATOM 2241 N ILE B 219 61. 775 58. 810 -27. ,513 1. 00 45. 70 N

ATOM 2242 CA ILE B 219 63. 118 58, 266 -27. 765 1. 00 46. 78 c

ATOM 2243 CB ILE B 219 63. 500 57. ,092 -26. ,847 1. 00 47. 02 c

ATOM 2244 CGI ILE B 219 63, 498 57, 538 -25. 373 1. 00 44. 51 c

ATOM 2245 CDl ILE B 219 62. 985 56. 469 -24. 398 1. 00 39. 61 c

ATOM 2246 CG2 ILE B 219 64. 921 56. 524 -27. 153 1. 00 44. 49 c

ATOM 2247 C ILE B 219 63. 344 58. 017 -29. 284 1. 00 47. 57 c

ATOM 2248 O ILE B 219 64. 316 58. 476 -29. 826 1. 00 47. 87 0

ATOM 2249 N LEU B 220 62. 393 57. 423 -29. 976 1. 00 49. 65 N

ATOM 2250 CA LEU B 220 62. 619 57. 039 -31. 372 1. 00 51. 27 C

ATOM 2251 CB LEU B 220 61. 497 56. 111 -31. 869 1. 00 49. 71 C

ATOM 2252 CG LEU B 220 61. 367 54. 883 -30. 968 1. 00 48. 98 C

ATOM 2253 CDl LEU B 220 60. 187 53. 926 -31. 245 1. 00 44. 27 c

ATOM 2254 CD2 LEU B 220 62. 713 54. 123 -31. 005 1. 00 52. 12 c

ATOM 2255 C LEU B 220 62. 824 58. 298 -32. 244 1. 00 54. 49 c

ATOM 2256 O LEU B 220 63. 791 58. 368 -33. 043 1. 00 56. 65 0

ATOM 2257 N GLU B 221 61. 953 59. 306 -32. 039 1. 00 56. 01 N

ATOM 2258 CA GLU B 221 62. 075 60. 679 -32. 586 1. 00 55. 26 C

ATOM 2259 CB GLU B 221 61. 046 61. 578 -31. 981 1. 00 54. 62 C ATOM 2260 CG GLU B 221 59.874 61.841 -32.863 1.00 56.30 c

ATOM 2261 CD GLU B 221 58 .748 62 .465 -32 .069 1 .00 59 .54 c

ATOM 2262 OEl GLU B 221 58 .981 63 .549 -31 .434 1 .00 61 .66 O

ATOM 2263 OE2 GLU B 221 57 .665 61 .823 -32 .014 1 .00 61 .19 0

ATOM 2264 C GLU B 221 63 .382 61 .337 -32 .285 1 .00 55 .27 c

ATOM 2265 O GLU B 221 64 .074 61 .757 -33 .210 1 .00 56 .64 0

ATOM 2266 N LEU B 222 63 .740 61 .501 -31 .023 1 .00 54 .61 N

ATOM 2267 CA LEU B 222 65 .009 62 .153 -30 .780 1 .00 56 .67 C

ATOM 2268 CB LEU B 222 65 .364 62 .281 -29 .311 1 .00 54 .91 C

ATOM 2269 CG LEU B 222 66 .813 62 .650 -29 .005 1 .00 55 .55 C

ATOM 2270 CDl LEU B 222 67 .214 64 .118 -29 .394 1 .00 54 .23 c

ATOM 2271 CD2 LEU B 222 67 .134 62 .359 -27 .549 1 .00 57 .22 c

ATOM 2272 C LEU B 222 66 .116 61 .396 -31 .587 1 .00 59 .82 c

ATOM 2273 O LEU B 222 67 .014 62 .049 -32 .147 1 .00 60 .62 0

ATOM 2274 N ALA B 223 66 .031 60 .050 -31 .681 1 .00 61 .61 N

ATOM 2275 CA ALA B 223 67 .037 59 .260 -32 .393 1 .00 62 .82 C

ATOM 2276 CB ALA B 223 66 .915 57 .783 -32 .125 1 .00 62 .44 C

ATOM 2277 C ALA B 223 67 .051 59 .555 -33 .882 1 .00 63 .23 C

ATOM 2278 O ALA B 223 68 .097 59 .802 -34 .390 1 .00 63 .76 O

ATOM 2279 N LYS B 224 65 .927 59 .551 -34 .577 1 .00 65 .01 N

ATOM 2280 CA LYS B 224 65 .953 60 .030 -35, .951 1 .00 67 .73 C

ATOM 2281 CB LYS B 224 64 .619 59 .867 -36 .647 1 .00 67 .41 C

ATOM 2282 CG LYS B 224 64 .077 58 .447 -36 .572 1 .00 71 .53 c

ATOM 2283 CD LYS B 224 63 .621 57 .917 -37 .957 1 .00 78 .32 c

ATOM 2284 CE LYS B 224 62 .922 56 .540 -37 .894 1 .00 81 .14 c

ATOM 2285 NZ LYS B 224 61 .425 56 .719 -37 .852 1 .00 82 .42 N

ATOM 2286 C LYS B 224 66. .528 61. .469 -36, .078 1, .00 69 .53 C

ATOM 2287 O LYS B 224 67 .293 61 .743 -37 .012 1 .00 70 .98 O

ATOM 2288 N SER B 225 66 .245 62 .371 -35 .140 1 .00 70 .61 N

ATOM 2289 CA SER B 225 66 .843 63 .718 -35, .218 1, .00 71 .96 C

ATOM 2290 CB SER B 225 66. .596 64 .572 -33 .976 1 .00 71 .34 C

ATOM 2291 OG SER B 225 65. .214 64 .755 -33, .860 1 .00 7 .14 O

ATOM 2292 C SER B 225 68, .324 63, .627 -35, ,393 1, .00 72, .88 C

ATOM 2293 O SER B 225 68. .841 64, .149 -36, .365 1, .00 73, .86 O

ATOM 2294 N LEU B 226 68. .969 62 .923 -34 .461 1 .00 73 .61 N

ATOM 2295 CA LEU B 226 70, .405 62 .969 -34, .171 1, .00 74, .41 C

ATOM 2296 CB LEU B 226 70, .609 62 .489 -32, .744 1, .00 73 .79 C

ATOM 2297 CG LEU B 226 70. .288 63, .470 -31, .645 1, .00 74 .68 C

ATOM 2298 CDl LEU B 226 70. .767 62, .849 -30. .331 1. .00 76. .80 C

ATOM 2299 CD2 LEU B 226 70. ,945 64, .859 -31. .901 1. ,00 74, .97 C

ATOM 2300 C LEU B 226 71. 290 62, ,135 -35. .110 1. .00 75, .30 C

ATOM 2301 O LEU B 226 72. .524 62 .053 -34. .924 1. .00 75, .37 O

ATOM 2302 N LYS B 227 70. .619 61 .521 -36. .093 1. .00 76, .58 N

ATOM 2303 CA LYS B 227 71. ,173 60, ,611 -37. ,100 1. .00 77, .53 C

ATOM 2304 CB LYS B 227 72. ,385 61, ,226 -37. ,851 1. .00 78. ,27 C

ATOM 2305 CG LYS B 227 72. ,119 62, ,643 -38. ,548 1. ,00 81. ,84 C

ATOM 2306 CD LYS B 227 73. 443 63, ,419 -38. 911 1. ,00 85. .43 C

ATOM 2307 CE LYS B 227 73, ,259 64 .945 -38. .784 1. ,00 88, .78 C

ATOM 2308 NZ LYS B 227 73, .267 65 .425 -37, .349 1. ,00 87. .35 N

ATOM 2309 C LYS B 227 71. ,438 59, .213 -36. ,515 1, ,00 76. .93 C

ATOM 2310 O LYS B 227 71. ,200 58, .232 -37. .213 1. ,00 77. .95 O

ATOM 2311 N VAL B 228 71. ,881 59, ,160 -35. ,246 1. ,00 75. .65 N

ATOM 2312 CA VAL B 228 72. 150 57, ,974 -34. 390 1. 00 74. 06 C

ATOM 2313 CB VAL B 228 72. 570 58, ,487 -33. 003 1. 00 73. 83 C

ATOM 2314 CGI VAL B 228 73. .047 57 .363 -32. ,115 1, ,00 74. ,80 C

ATOM 2315 CG2 VAL B 228 73, .619 59, .547 -33, ,115 1. 00 74. 65 c

ATOM 2316 C VAL B 228 71, ,066 56, .848 -34. ,151 1. 00 73. ,54 c

ATOM 2317 O VAL B 228 69, ,866 57, .010 -34. ,475 1, ,00 73. ,12 0

ATOM 2318 N ASP B 229 71, 528 55. .719 -33, 573 1. 00 72. 48 N

ATOM 2319 CA ASP B 229 70, 719 54, .552 -33, 127 1. 00 72. 47 c

ATOM 2320 CB ASP B 229 71, .611 53, .269 -32, ,949 1. ,00 72. ,65 c

ATOM 2321 CG ASP B 229 70. ,773 51, .950 -32. .742 1. 00 75. 69 c

ATOM 2322 OD1 ASP B 229 70. ,769 51, .382 -31. .613 1. 00 74. .87 0

ATOM 2323 OD2 ASP B 229 70. ,071 51, ,405 -33. ,654 1. ,00 78. ,20 0

ATOM 2324 C ASP B 229 70, 015 54, ,818 -31, 759 1. 00 71. 15 c

ATOM 2325 O ASP B 229 70. 661 55, .236 -30, 783 1. 00 71. 84 o

ATOM 2326 N PRO B 230 68. 743 54. .466 -31. ,649 1, 00 69. .83 N

ATOM 2327 CA PRO B 230 67, ,993 54, .664 -30. ,394 1. 00 69. .13 c

ATOM 2328 CB PRO B 230 66. ,672 53, .903 -30. ,638 1. 00 69. .73 c

ATOM 2329 CG PRO B 230 66. 562 53. .670 -32. ,149 1. ,00 69. ,20 c

ATOM 2330 CD PRO B 230 67, 937 53. .807 -32. 699 1. 00 70. 18 c

ATOM 2331 C PRO B 230 68, 710 54, .117 -29, 146 1. 00 68. 20 c

ATOM 2332 O PRO B 230 68. 736 54. ,849 -28. ,160 1. 00 67. 33 0

ATOM 2333 N ARG B 231 69. 318 52. ,920 -29. 235 1. 00 68. 22 N

ATOM 2334 CA ARG B 231 69. ,960 52, .188 -28. ,124 1. 00 69. 07 C

ATOM 2335 CB ARG B 231 70. 423 50, ,796 -28, ,548 1. 00 69. .61 C

ATOM 2336 CG ARG B 231 69. 394 4g. .673 -28. 516 1. 00 71. 55 c ATOM 2337 CD ARG B 231 69.474 48.753 -29.698 1.00 79.97 C

ATOM 2338 NE ARG B 231 68 .149 48 .357 -30 .211 1 .00 87 .25 N

ATOM 2339 CZ ARG B 231 67 .948 47 .546 -31 .264 1 .00 90 .61 C

ATOM 2340 NH1 ARG B 231 68 .995 47 .052 -31 .942 1 .00 91 .45 N

ATOM 2341 NH2 ARG B 231 66 .705 47 .239 -31 .652 1 .00 91 .72 N

ATOM 2342 C ARG B 231 71 .157 52 .879 -27 .484 1 .00 69 .48 C

ATOM 2343 O ARG B 231 71 .693 52 .386 -26 .475 1 .00 68 .89 O

ATOM 2344 N ALA B 232 71 .563 54 .015 -28 .058 1 .00 69 .47 N

ATOM ₂345 CA ALA B 232 72 .878 54 .540 -27 .784 1 .00 70 .00 C

ATOM 2346 CB ALA B 232 73 .802 54 .359 -29 .017 1 .00 70 .48 C

ATOM 2347 C ALA B 232 72 .742 55 .971 -27 .464 1 .00 70 .41 C

ATOM 2348 O ALA B 232 73 .736 56 .654 -27 .230 1 .00 70 .90 O

ATOM 2349 N CYS B 233 71 .490 56 .425 -27 .463 1 .00 70 .30 N

ATOM 2350 CA CYS B 233 71 .160 57 .811 -27 .238 1 .00 68 .64 C

ATOM 2351 CB CYS B 233 71 .072 58 .493 -28 .592 1 .00 68 .93 C

ATOM 2352 SG CYS B 233 69 .368 58 .655 -29 .133 1 .00 74 .17 S

ATOM 2353 C CYS B 233 69. .887 58 .070 -26 .374 1 .00 66 .64 C

ATOM 2354 O CYS B 233 69 .689 59, .200 -25 .927 1 .00 67 .63 O

ATOM 2355 N PHE B 234 69 .040 57 .056 -26 .146 1 .00 63 .gs N

ATOM 2356 CA PHE B 234 67 .960 57 .107 -25 .118 1 .00 60 .58 C

ATOM 2357 CB PHE B 234 67 .305 55, .732 -24 .887 1 .00 60 .46 C

ATOM 2358 CG PHE B 234 68 .097 54, .796 -23 .970 1 .00 56 .90 c

ATOM 2359 CDl PHE B 234 67 .872 54, .791 -22 .610 1 .00 52 .73 c

ATOM 2360 CE1 PHE B 234 68 .593 53 .953 -21 .763 1 .00 55 .53 c

ATOM 2361 CZ PHE B 234 69 .546 53, .073 -22 .300 1 .00 54 .30 c

ATOM 2362 CE2 PHE B 234 69, .731 53, .053 -23 .691 1 .00 51 .56 c

ATOM 2363 CD2 PHE B 234 69, .027 53 .910 -24 .499 1 .00 52 .84 c

ATOM 2364 C PHE B 234 68 .295 57, .738 -23 .773 1 .00 59 .62 c

ATOM 2365 O PHE B 234 67, .457 58, .405 -23 .188 1 .00 59 .64 0

ATOM 2366 N ARG B 235 69, .526 57, .581 -23 .296 1. .00 58, .04 N

ATOM 2367 CA ARG B 235 69 .926 58 .128 -22 .000 1 .00 57 .34 C

ATOM 2368 CB ARG B 235 71, ,342 57, .671 -21 .586 1. .00 56 .72 c

ATOM 2369 CG ARG B 235 71, ,353 56, .492 -20 .539 1, .00 61, .57 c

ATOM 2370 CD ARG B 235 72, .742 56. .024 -19 .935 1. .00 62, .41 c

ATOM 2371 NE ARG B 235 72. .881 54, .566 -20 .048 1. .00 68 .30 N

ATOM 2372 CZ ARG B 235 73, .150 53, .895 -21 .204 1. .00 71, .76 C

ATOM 2373 NH1 ARG B 235 73, .349 54, .583 -22 .338 1. .00 73, .98 N

ATOM 2374 NH2 ARG B 235 73. ,234 52. .543 -21, .239 1. ,00 68. .26 N

ATOM 2375 C ARG B 235 69. ,835 59. .625 -21 .992 1, ,00 56 ,79 C

ATOM 2376 O ARG B 235 69. .779 60. .270 -20 .959 1 .00 56. .35 O

ATOM 2377 N GLN B 236 69. .857 60. ,214 -23, .164 1. ,00 57, .52 N

ATOM 2378 CA GLN B 236 69. .961 61. ,656 -23 .169 1, ,00 57, .27 C

ATOM 2379 CB GLN B 236 71, .077 62, .133 -24 .086 1 .00 57 .21 C

ATOM 2380 CG GLN B 236 70. ,865 61. ,912 -25 .540 1, .00 62, .10 C

ATOM 2381 CD GLN B 236 71. ,903 62. ,774 -26 .361 1, .00 70. .22 C

ATOM 2382 OEl GLN B 236 72. 967 62. .254 -26, .804 1, ,00 68, .77 O

ATOM 2383 NE2 GLN B 236 71. .591 64, .070 -26 .538 1, .00 66, .41 N

ATOM 2384 C GLN B 236 68, .559 62, .324 -23 .317 1, .00 55, .05 C

ATOM 2385 O GLN B 236 68. ,370 63. .489 -22 .950 1. .00 54, .54 O

ATOM 2386 N PHE B 237 67. ,584 61. .523 -23, .734 1. .00 52. ,48 N

ATOM 2387 CA PHE B 237 66. .175 61. .883 -23 .521 1. .00 51, .11 C

ATOM 2388 CB PHE B 237 65. ,243 60. ,853 -24 .131 1. .00 50, .48 C

ATOM 2389 CG PHE B 237 63. .796 61. ,162 -23, .876 1. .00 51. ,30 C

ATOM 2390 CDl PHE B 237 63. ,119 62. ,101 -24, .658 1. ,00 44. ,72 C

ATOM 2391 CE1 PHE B 237 61. ,854 62. ,432 -24, .390 1. .00 42. .66 C

ATOM 23g2 CZ PHE B 237 61. ,157 61. ,843 -23, .321 1. ,00 47, ,58 C

ATOM 23g3 CE2 PHE B 237 61. ,785 60, ,931 -22, .530 1. ,00 50. ,97 C

ATOM 23g4 CD2 PHE B 237 63. 130 60. 584 -22, .811 1. ,00 49. ,ιg C

ATOM 23 5 C PHE B 237 65. ,871 62, ,044 -22, .007 1, ,00 51, ,04 C

ATOM 2396 O PHE B 237 65. ,367 63, .083 -21 .561 1, ,00 49. .37 O

ATOM 2397 N PHE B 238 66. ,262 61. .051 -21. .209 1, ,00 50. .03 N

ATOM 2398 CA PHE B 238 65. ,997 61. .131 -19. .800 1. ,00 50. 48 C

ATOM 2399 CB PHE B 238 66. .285 59. .811 -19, .144 1. .00 48, ,58 C

ATOM 2400 CG PHE B 238 65. ,263 58. ,783 -19. .501 1. .00 48. .51 C

ATOM 2401 CDl PHE B 238 65. ,561 57. ,741 -20, .364 1. ,00 46. .56 C

ATOM 2402 CE1 PHE B 238 64. ,587 56. ,807 -20, .740 1. .00 43. ,47 C

ATOM 2403 CZ PHE B 238 63. ,272 56. ,925 -20, ,212 1. .00 45. ,56 C

ATOM 2404 CE2 PHE B 238 62. .960 58. ,024 -19, .414 1, ,00 41, ,90 C

ATOM 2405 CD2 PHE B 238 63, .934 58, .935 -19, .081 1. ,00 45, ,31 c

ATOM 2406 C PHE B 238 66. .675 62. ,286 -19. ,138 1. 00 52. ,13 c

ATOM 2407 O PHE B 238 66. ,090 62. ,973 -18, .264 1. ,00 51, ,26 o

ATOM 2408 N THR B 239 67. .876 62, .559 -19, .644 1, ,00 53. ,74 N

ATOM 2409 CA THR B 239 68. .710 63. ,676 -19. .192 1, ,00 54. ,21 C

ATOM 2410 CB THR B 239 70. ,132 63. ,544 -19, ,829 1. ,00 54. ,93 C

ATOM 2411 OG1 THR B 239 70. ,853 62. ,560 -19, ,052 1. ,00 55. ,76 O

ATOM 2412 CG2 THR B 239 70. ,961 64. ,839 -19, .634 1. ,00 54. ,94 C

ATOM 2413 C THR B 239 68. ,080 64. ,994 -19, .510 1. ,00 53. ,65 C ATOM 2414 O THR B 239 68.058 65.872 -18.681 1.00 52.06 0

ATOM 2415 N LYS B 240 67 .529 65 .105 -20 .718 1 .00 54 .72 N

ATOM 2416 CA LYS B 240 66 .881 66 .322 -21 .115 1 .00 55 .77 C

ATOM 2417 CB LYS B 240 66 .868 66 .456 -22 .641 1 .00 57 .17 C

ATOM 2418 CG LYS B 240 68 .098 67 .329 -23 .372 1 .00 66 .31 C

ATOM 2419 CD LYS B 240 69 .396 67 .861 -22 .542 1 .00 74 .45 C

ATOM 2420 CE LYS B 240 69 .510 69 .448 -22 .416 1 .00 77 .48 C

ATOM 2421 NZ LYS B 240 69 .269 70 .161 -23 .718 1 .00 80 .09 N

ATOM 2422 C LYS B 240 65 .470 66 .437 -20 .412 1 .00 54 .93 C

ATOM 2423 O LYS B 240 65 .091 67 .535 -19 .906 1 .00 54 .97 O

ATOM 2424 N ILE B 241 64 .759 65 .322 -20 .272 1 .00 51 .85 N

ATOM 2425 CA ILE B 241 63 .473 65 .411 -19 .617 1 .00 51 .29 C

ATOM 2426 CB ILE B 241 62 .559 64 .250 -19 .937 1 .00 49 .65 C

ATOM 2427 CGI ILE B 241 61 .135 64 .765 -19 .938 1 .00 53 .61 C

ATOM 2428 CDl ILE B 241 60 .472 64 .677 -21 .208 1 .00 44 .83 c

ATOM 2429 CG2 ILE B 241 62 .587 63 .208 -18 .919 1 .00 48 .65 c

ATOM 2430 C ILE B 241 63 .511 65 .795 -18 .136 1 .00 52 .65 c

ATOM 2431 O ILE B 241 62 .677 66 .623 -17 .696 1 .00 52 .86 0

ATOM 2432 N LYS B 242 64 .495 65 .302 -17 .378 1 .00 52 .76 N

ATOM 2433 CA LYS B 242 64 .547 65 .612 -15 .943 1 .00 54 .02 C

ATOM 2434 CB LYS B 242 65 .610 64 .826 -15 .192 1 .00 54 .08 C

ATOM 2435 CG LYS B 242 65 .302 63 .366 -15 .052 1 .00 58 .46 C

ATOM 2436 CD LYS B 242 66 .582 62 ,503 -15 .173 1 .00 63 .32 C

ATOM 2437 CE LYS B 242 66 .968 61 .879 -13 .829 1 .00 66 .95 C

ATOM 2438 NZ LYS B 242 68 .431 61 .460 -13 .785 1 .00 70 .19 N

ATOM 2439 C LYS B 242 64 .711 67 .091 -15 .666 1 .00 54 .02 C

ATOM 2440 O LYS B 242 64 .292 67 .579 -14 .617 1 .00 5 .83 O

ATOM 2441 N THR B 243 65 .296 67 .843 -16. .574 1 .00 54 .32 N

ATOM 2442 CA THR B 243 65 .283 69 .278 -16 .297 1 .00 55 .27 C

ATOM 2443 CB THR B 243 66 .722 69 .833 -15 .955 1 .00 56 .93 C

ATOM 2444 OG1 THR B 243 67 .631 69 .585 -17 .061 1 .00 57 .73 O

ATOM 2445 CG2 THR B 243 67, .304 69 .095 -14, .697 1 .00 57, .80 C

ATOM 2446 C THR B 243 64, .628 70, .094 -17, .396 1 .00 53, .73 C

ATOM 2447 O THR B 243 65. .076 71, .218 -17, .695 1. .00 54, .72 O

ATOM 2448 N ALA B 244 63. .588 69 .556 -18 .024 1 .00 51 .06 N

ATOM 2449 CA ALA B 244 63. .058 70 .267 -19, .188 1 .00 48, .00 C

ATOM 2450 CB ALA B 244 62. .068 69. ,422 -ιg. ,879 1, ,00 47, .97 C

ATOM 2451 C ALA B 244 62. .401 71, .594 -18, .745 1, .00 45. .69 C

ATOM 2452 O ALA B 244 61. ,904 71, .719 -17. .624 1, .00 42. .88 O

ATOM 2453 N ASP B 245 62. ,391 72. .580 -19. .639 1 .00 43. .64 N

ATOM 2454 CA ASP B 245 61. .539 73, .754 -19. .415 1 .00 44, .38 C

ATOM 2455 CB ASP B 245 61, ,717 74, ,72g -20, .568 1, .00 45. .39 C

ATOM 2456 CG ASP B 245 63. 225 75. ,081 -20. .775 1, .00 54. .07 c

ATOM 2457 OD1 ASP B 245 63. ,956 75. .184 -19. ,707 1. .00 56. ,25 O

ATOM 2458 OD2 ASP B 245 63. ,766 75. .194 -21. .941 1. .00 61. ,00 o

ATOM 2459 C ASP B 245 60. 075 73. .397 -19, .200 1, .00 42. .56 c

ATOM 2460 O ASP B 245 59. ,591 72. .366 -ιg, .716 1, .00 41. .54 o

ATOM 2461 N ARG B 246 59. 414 74. 195 -18. 359 1. .00 40. .76 N

ATOM 2462 CA ARG B 246 57. 66 74. ,147 -18. .i77 1, .00 38. .61 C

ATOM 2463 CB ARG B 246 57. ,492 75. ,470 -17. .515 1, ,00 37. ,00 C

ATOM 2464 CG ARG B 246 56. 058 75. ,435 -17. .125 1. ,00 38. ,44 C

ATOM 2465 CD ARG B 246 55. 466 76, .772 -16, .584 1, .00 39. .36 c

ATOM 2466 NE ARG B 246 55. 534 77. 924 -17. ,488 1. ,00 34. ,69 N

ATOM 2467 CZ ARG B 246 56. 424 78. 937 -17. 359 1. 00 46. 89 C

ATOM 2468 NH1 ARG B 246 57. 353 78. ,888 -16. .398 1. ,00 48. ,34 N

ATOM 2469 NH2 ARG B 246 56. 433 79. 994 -18. .199 1. ,00 40. ,53 N

ATOM 2470 C ARG B 246 57. 278 73. ,950 -19. .565 1. ,00 36. ,88 C

ATOM 2471 O ARG B 246 56. 367 73. 179 -19. 676 1. 00 37. ,70 O

ATOM 2472 N GLN B 247 57. 707 74. 660 -20. 599 1. 00 34. ,51 N

ATOM 2473 CA GLN B 247 56. 917 74. 735 -21. 874 1. 00 35. 16 C

ATOM 2474 CB GLN B 247 57. 484 75. ,7go -22. ,824 1. ,00 32. ,93 C

ATOM 2475 CG GLN B 247 57. 191 77. ,229 -22. .480 1. ,00 35. ,93 C

ATOM 2476 CD GLN B 247 58. 224 77. 923 -21. 492 1. ,00 39. ,29 C

ATOM 2477 OEl GLN B 247 58. 145 79. 107 -21, 294 1. ,00 47. ,38 O

ATOM 2478 NE2 GLN B 247 59. 117 77. 207 -20. 931 1. 00 33. 13 N

ATOM 2479 C GLN B 247 57. 013 73. 401 -22. 612 1. 00 35. .48 C

ATOM 2480 O GLN B 247 56. 041 72. ,903 -23. 228 1. ,00 35. .07 O

ATOM 2481 N TYR B 248 58. 204 72. 801 -22. 492 1. 00 36. .02 N

ATOM 2482 CA TYR B 248 58. 449 71. 502 -23. 042 1. 00 36. 01 C

ATOM 2483 CB TYR B 248 59. 941 71. 113 -22. 754 1. 00 37. 21 C

ATOM 2484 CG TYR B 248 60. 240 6g. 787 -23. 386 1. 00 38. 34 C

ATOM 2485 CDl TYR B 248 60. 740 69 . 733 -24. 666 1. 00 35. .71 C

ATOM 2486 CE1 TYR B 248 60. 960 68. 468 -25. 267 1. 00 39. 11 C

ATOM 2487 CZ TYR B 248 60. 617 67. 284 -24. 606 1. 00 42. 11 C

ATOM 2488 OH TYR B 248 60. 857 66. 097 -25. 230 1. 00 46. 58 O

ATOM 2489 CE2 TYR B 248 60. 055 67. 296 -23. 338 1. 00 43. 05 C

ATOM 2490 CD2 TYR B 248 59. 880 68. 568 -22. 721 1. 00 36. 48 C ATOM 2491 C TYR B 248 57.443 70.478 -22.408 1.00 36.44 c

ATOM 2492 O TYR B 248 56 .731 69 .780 -23 .088 1 .00 37 .27 0

ATOM 2493 N MET B 249 57 .347 70 .465 -21 .078 1 .00 38 .33 N

ATOM 2494 CA MET B 249 56 .450 69 .545 -20 .349 1 .00 37 .45 C

ATOM 2495 CB MET B 249 56 .701 69 .652 -18 .829 1 .00 36 .76 C

ATOM 2496 CG MET B 249 58 .063 69 .075 -18 .355 1 .00 41 .21 C

ATOM 2497 SD MET B 249 58 .155 67 .220 -18 .782 1 .00 48 .45 S

ATOM 2498 CE MET B 249 59 .109 67 .595 -19 .701 1 .00 41 .79 C

ATOM 2499 C MET B 249 54 .981 69 .830 -20 .649 1 .00 36 .03 C

ATOM 2500 O MET B 249 54 .160 68 .903 -20 .594 1 .00 33 .50 O

ATOM 2501 N GLU B 250 54 .651 71 .110 -20 .923 1 .00 33 .89 N

ATOM 2502 CA GLU B 250 53 .304 71 .380 -21 .413 1 .00 35 .03 C

ATOM 2503 CB GLU B 250 52 .919 72 .886 -21 .400 1 .00 35 .52 C

ATOM 2504 CG GLU B 250 52 .718 73 .332 -19 .942 1 .00 37 .32 C

ATOM 2505 CD GLU B 250 52 .929 74 .870 -19 .757 1 .00 43 .15 C

ATOM 2506 OEl GLU B 250 53 .625 75 .576 -20 .534 1 .00 38 .15 O

ATOM 2507 OE2 GLU B 250 52 .420 75 .386 -18 .777 1 .00 49 .82 O

ATOM 2508 C GLU B 250 53 .011 70 .689 -2 .778 1 .00 34 .27 C

ATOM 2509 O GLU B 250 51 .943 70 .107 -22 .929 1 .00 32 .00 O

ATOM 2510 N GLY B 251 53 .982 70 .734 -23 .720 1 .00 33 .93 N

ATOM 2511 CA GLY B 251 53 .809 70 .048 -25 .004 1 .00 33 .03 C

ATOM 2512 C GLY B 251 53 .836 68 .54g -24, .900 1 .00 32 .78 C

ATOM 2513 O GLY B 251 52 .959 67 .910 -25 .431 1 .00 33 .57 O

ATOM 2514 N PHE B 252 54 .802 67 .996 -24 .152 1 .00 31 .79 N

ATOM 2515 CA PHE B 252 54 .735 66 .627 -23, .678 1. .00 31 .17 C

ATOM 2516 CB PHE B 252 55 .807 66 .403 -22 .616 1 .00 30 .89 C

ATOM 2517 CG PHE B 252 55 .883 64 .990 -22 .142 1 .00 29 .87 C

ATOM 2518 CDl PHE B 252 56 .882 64 .154 -22, .600 1. .00 30 .16 C

ATOM 2519 CE1 PHE B 252 56, .891 6 .806 -22 .203 1 .00 36 .47 C

ATOM 2520 CZ PHE B 252 55 .941 62 .313 -21, .342 1, .00 35, .47 C

ATOM 2521 CE2 PHE B 252 54, .925 63 .162 -20, .869 1, .00 39, .62 C

ATOM 2522 CD2 PHE B 252 54. .914 64 .481 -21 .296 1 .00 31 .27 C

ATOM 2523 C PHE B 252 53. .311 66, .240 -23, .152 1, .00 32, .44 C

ATOM 2524 O PHE B 252 52. .693 65 .332 -23, .680 1, .00 33, .16 O

ATOM 2525 N ASN B 253 52, .727 66. .980 -22, .220 1 .00 31 .94 N

ATOM 2526 CA ASN B 253 51. .342 66, .712 -21, .806 1, .00 31. .11 C

ATOM 2527 CB ASN B 253 51. .001 67 .381 -20, .484 1, .00 28, .72 C

ATOM 2528 CG ASN B 253 51. .784 66, .707 -19. .333 1, .00 36, .28 C

ATOM 2529 OD1 ASN B 253 51. .713 65 .472 -19. ,134 1, .00 42, .60 O

ATOM 2530 ND2 ASN B 253 52. .597 67 .459 -18. .646 1, .00 39, .18 N

ATOM 2531 C ASN B 253 50. .198 66, .799 -22. ,841 1. .00 31, .68 C

ATOM 2532 O ASN B 253 49. ,264 65, .947 -22, .779 1, ,00 32. .10 O

ATOM 2533 N ASP B 254 50, .281 67 .770 -23, .765 1, .00 31. .11 N

ATOM 2534 CA ASP B 254 49. ,323 67. .925 -24. .841 1, ,00 31. .58 C

ATOM 2535 CB ASP B 254 49. ,664 69. .177 -25. .676 1, ,00 31. .53 C

ATOM 2536 CG ASP B 254 49. .386 70. .499 -24. .923 1. ,00 38. ,79 C

ATOM 2537 OD1 ASP B 254 48. .704 70. .526 -23. ,864 1. ,00 42. .74 O

ATOM 2538 OD2 ASP B 254 49. ,847 71, .600 -25. .327 1. .00 46. .44 O

ATOM 2539 C ASP B 254 49. ,436 66, .714 -25. .751 1. .00 32. .31 C

ATOM 2540 O ASP B 254 48. ,416 66, .202 -26. .143 1. .00 32. ,49 O

ATOM 2541 N GLU B 255 50. ,678 66. .267 -26. .068 1. .00 32. .11 N

ATOM 2542 CA GLU B 255 50. .882 65, .111 -26, .971 1. .00 33. .21 C

ATOM 2543 CB GLU B 255 52. ,322 65. .076 -27. ,507 1. .00 31. .86 C

ATOM 2544 CG GLU B 255 52. 540 66. ,221 -28. ,521 1. .00 32. .55 C

ATOM 2545 CD GLU B 255 53. ,902 66, ,204 -29. .155 1. .00 35. .22 C

ATOM 2546 OEl GLU B 255 54. .333 65, .062 -29. .452 1. .00 40. ,73 O

ATOM 2547 OE2 GLU B 255 54. 567 67. ,276 -29. 359 1. ,00 37. ,25 O

ATOM 2548 C GLU B 255 50. 441 63. .831 -26. .233 1. ,00 33. ,21 C

ATOM 2549 O GLU B 255 49. .786 63. ,014 -26. .787 1. .00 34. .22 O

ATOM 2550 N LEU B 256 50. 693 63. ,694 -24. .951 1. ,00 33. .82 N

ATOM 2551 CA LEU B 256 50. ,131 62. ,552 -24, .245 1, .00 34. ,40 C

ATOM 2552 CB LEU B 256 50. ,648 62, ,582 -22. ,799 1. .00 33. 92 C

ATOM 2553 CG LEU B 256 50. .084 61, ,554 -21. ,777 1. .00 35. ,17 C

ATOM 2554 CDl LEU B 256 50. ,149 60, ,221 -22, .379 1. .00 27. ,42 C

ATOM 2555 CD2 LEU B 256 50. 953 61, .671 -20. ,514 1. .00 29. 50 C

ATOM 2556 C LEU B 256 48. ,568 62, .481 -24. ,304 1. ,00 34. 97 C

ATOM 2557 O LEU B 256 47. 975 61, ,411 -24. ,571 1. .00 35. 18 O

ATOM 2558 N GLU B 257 47. ,905 63, .574 -23. ,964 1. ,00 35. 10 N

ATOM 2559 CA GLU B 257 46. ,407 63, .698 -24. .011 1. ,00 35. 88 C

ATOM 2560 CB GLU B 257 45. 881 65, .090 -23. .569 1. ,00 32. 05 C

ATOM 2561 CG GLU B 257 45. ,930 65, .366 -22. ,079 1. ,00 40. 86 C

ATOM 2562 CD GLU B 257 45. ,240 64 .249 -21. ,258 1. ,00 53. 30 C

ATOM 2563 OEl GLU B 257 44. 046 63, ,910 -21. 562 1. ,00 53. 73 O

ATOM 2564 OE2 GLU B 257 45. ,924 63 .642 -20, ,350 1. ,00 53. 96 O

ATOM 2565 C GLU B 257 45. 883 63, .470 -25, 438 1. 00 34. 84 C

ATOM 2566 O GLU B 257 44. 907 62, ,788 -25. 610 1. ,00 35. 13 O

ATOM 2567 N ALA B 258 46. 512 64 .062 -26. ,440 1. ,00 33. 89 N ATOM 2568 CCAA ALA B 258 46.042 63.806 -27.818 1.00 35.05 C ATOM 2569 CCBB ALA B 258 46 .gog 64 .656 -28 .836 1 .00 30 .83 c ATOM 2570 CC ALA B 258 46 .153 62 .245 -28 .og7 1 .00 36 .48 c ATOM 2571 OO ALA B 258 45 .202 61 .600 -28 .619 1 .00 37 .61 O ATOM 2572 NN PHE B 259 47 .305 61 .650 -27 .7₂g 1 .00 35 .5 N ATOM 2573 CCAA PHE B 259 47 .534 60 .205 -27 .go9 1 .00 36 .og C ATOM 2574 CCBB PHE B 259 48 .943 59 .811 -27 .409 1 .00 37 .23 C ATOM 2575 CCGG PHE B 259 49 .208 58 .350 -27 .344 1 .00 38 .g3 C ATOM 2576 CDl PHE B 259 49 .951 57 .734 -28 .369 1 .00 44 .25 C ATOM 2577 CE1 PHE B 259 50 .221 56 .277 -28 .340 1 .00 44 .89 c ATOM 2578 CZ PHE B 259 49 .75g 55 .513 -27 .232 1 .00 41 .20 c ATOM 2579 CE2 PHE B 259 49 .012 56 .132 -26 .184 1 .00 38 .87 c ATOM 2580 CD2 PHE B 259 48 .755 57 .559 -26 .246 1 .00 38 .40 c ATOM 2581 CC PHE B 259 46 .447 59 .375 -27 .258 1 .00 36 .11 c ATOM 2582 OO PHE B 225599 45 .g₂ι 58 .418 -27 .838 1 .00 35 .52 0 ATOM 2583 NN LYS B 226600 46 .099 59 .742 -26 .048 1 .00 35 .88 N ATOM 2584 CCAA LYS B 226600 45 .124 59 .019 -25 .317 1 .00 36 .59 C ATOM 2585 CCBB LYS B 226600 44 .959 59 .633 -23 .943 1 .00 34 .40 C ATOM 2586 CCGG LYS B 260 46 .069 59 .205 -23 .014 1 .00 41 .23 C ATOM 2587 CCDD LYS B 260 45 .793 59 .420 -21 .491 1 .00 37 .69 c ATOM 2588 CCEE LYS B 260 46 .196 60 .782 -20 .984 1 .00 41 .18 c ATOM 258g NNZZ LYS B 260 46 .596 60 .739 -19 .448 1. .00 41 .90 N ATOM 2590 CC LYS B 260 43 .771 59 .135 -26 .008 1 .00 40 .02 C ATOM 2591 OO LYS B 260 42 .902 58 .197 -25 .845 1 .00 39 .04 O ATOM 2592 NN GLU B 261 43 .553 60 .266 -26 .739 1 .00 40 .40 N ATOM 2593 CCAA GLU B 261 42 .272 60 .477 -27 .460 1 .00 41 .25 C ATOM 2594 CCBB GLU B 261 42 .078 61 .986 -27 .810 1 .00 43 .27 C ATOM 2595 CCGG GLU B 261 41 .639 62, .823 -26 .626 1 .00 46 .45 c ATOM 2596 CCDD GLU B 261 40 .257 62 .333 -25 .124 1, .00 61 .72 c ATOM 2597 OEl GLU B 261 40 .177 61 .666 -25 .023 1 .00 63 .10 o ATOM 2598 OE2 GLU B 261 39 .221 62, .578 -26 .849 1 .00 67 .34 o ATOM 2599 CC GLU B 261 42 .221 59, .577 -28 .717 1 .00 39 .12 c ATOM 2600 OO GLU B 261 41, .258 58, .877 -28 .969 1. .00 39 .26 0 ATOM 2601 NN ARG B 262 43, .292 59. .555 -29, .480 1. .00 37 .69 N ATOM 2602 CCAA ARG B 262 43 .39g 58, .598 -30 .545 1 .00 37 .27 C ATOM 2603 CCBB ARG B 262 44 .706 58, .755 -31 .242 1 .00 35 .66 C ATOM 2604 CCGG ARG B 262 44, .827 60, .261 -31. .782 1. .00 35 .94 C ATOM 2605 CCDD ARG B 262 45. .792 60. .304 -32, .902 1. .00 33 .13 C ATOM 2606 NNEE ARG B 262 47. .028 59. .894 -32, .330 1. .00 42, .15 N ATOM 2607 CCZZ ARG B 262 47. ,866 60. ,754 -31. .747 1. .00 46, .86 C ATOM 2608 NH1 ARG B 262 47. .589 62, .092 -31. .730 1. .00 46 .25 N ATOM 2609 NH2 ARG B 262 48. .988 60. .277 -31. .230 1, .00 42 .41 N ATOM 2610 CC ARG B 262 43. .166 57, ,114 -30, .003 1. .00 39 .55 C ATOM 2611 OO ARG B 262 42. .426 56. ,359 -30. .614 1, .00 39, .80 O ATOM 2612 NN VAL B 263 43. .695 56. ,758 -28, .827 1. ,00 38, .81 N ATOM 2613 CCAA VAL B 263 43. ,545 55. ,398 -28. .342 1. .00 38, .19 C ATOM 2614 CCBB VAL B 263 44, .376 55. ,100 -27. .054 1, .00 37 .10 C ATOM 2615 CGI VAL B 263 43. ,784 53. ,877 -26, .29g 1. .00 32, .03 C ATOM 2616 CG2 VAL B 263 45. ,806 54. ,971 -27, .357 1. ,00 31, .35 C ATOM 2617 C VAL B 263 42. ,081 55. ,270 -28. .012 1. ,00 39. .16 C ATOM 2618 OO VAL B 263 41. ,453 54. 265 -28. 325 1. ,00 39. .69 O ATOM 2619 NN ARG B 264 41. 481 56. 267 -27. .412 1. 00 40. .49 N ATOM 2620 CCAA ARG B 264 40, ,061 56. ,040 -27. ,158 1. ,00 42, .47 C ATOM 2621 CCBB ARG B 264 39. ,465 57. ,107 -26. ,234 1. ,00 41. .07 C ATOM 2622 CCGG ARG B 264 40. ,003 57. ,070 -24. .870 1. ,00 39. ,17 C ATOM 2623 CCDD ARG B 264 39. ,639 58. 349 -24. 092 1. 00 44. ,20 C ATOM 2624 NNEE ARG B 264 40. ,343 58. 324 -22. 827 1. 00 49. ,19 N ATOM 2625 CCZZ ARG B 264 41. 129 59. 293 -22. 355 1. 00 47. ,11 C ATOM 2626 NH1 ARG B 264 41. ,307 60. ,473 -22. ,9 7 1. ,00 40. ,32 N ATOM 2627 NH2 ARG B 264 41. ,727 59. ,055 -21. 206 1. ,00 46. ,06 N ATOM 2628 C ARG B 264 39. 218 55. 907 -28. 487 1, 00 44. .69 C ATOM 2629 OO ARG B 264 38. 199 55. 214 -28. 499 1. 00 45. 13 O ATOM 2630 NN GLY B 265 39. 608 56. 620 -29. 551 1. 00 44. 08 N ATOM 2631 CCAA GLY B 265 38. 832 56. 574 -30. 759 1. 00 44. 07 C ATOM 2632 CC GLY B 265 39. 030 55. 176 -31. 322 1. 00 45. ,94 C ATOM 2633 OO GLY B 265 38. 046 54. 612 -31. 752 1. 00 46. ,29 O ATOM 2634 NN ARG B 266 40. 265 54. 622 -31. 339 1. 00 45. ,87 N ATOM 2635 CCAA ARG B 266 40. 477 53. 212 -31. 689 1. 00 47. 03 C ATOM 2636 CCBB ARG B 266 41. 927 52. 839 -31. 916 1. 00 48. 00 C ATOM 2637 CCGG ARG B 266 42. 485 53. 741 -33. 082 1. 00 50. 53 C ATOM 2638 CCDD ARG B 266 43. 735 53. 340 -33. 762 1. 00 62. ,16 C ATOM 2639 NNEE ARG B 266 43. 788 51. 935 -34. 210 1. 00 70. .79 N ATOM 2640 CCZZ ARG B 266 44. 929 51. 292 -34. 566 1. 00 73. .07 C ATOM 2641 NH1 ARG B 266 46. 112 51. 919 -34. 521 1. 00 70. 87 N ATOM 2642 NH2 ARG B 266 44. 872 50. 019 -34. 958 1. 00 74. 06 N ATOM 2643 C ARG B 266 39. 706 52. 174 -30. 880 1. 00 47. 14 C ATOM 2644 O ARG B 266 39. 153 51. 257 -31. 489 1. 00 4g. .30 O ATOM 2645 N ALA B 267 39.558 52.355 -29.575 1.00 45.93 N

ATOM 2646 CA ALA B 267 38 .858 51 .381 -28 .768 1 .00 45 .76 C

ATOM 2647 CB ALA B 267 38 .946 51 .635 -27 .157 1 .00 41 .13 C

ATOM 2648 C ALA B 267 37 .403 51 .488 -29 .200 1 .00 47 .92 C

ATOM 2649 O ALA B 267 36 .671 50 .422 -29 .236 1 .00 49 .10 O

ATOM 2650 N LYS B 268 36 .919 52 .729 -29 .376 1 .00 47 .06 N

ATOM 2651 CA LYS B 268 35 .509 52 .904 -29 .648 1 .00 49 .70 C

ATOM 2652 CB LYS B 268 35 .142 54 .381 -29 .637 1 .00 51 .75 C

ATOM 2653 CG LYS B 268 33 .976 54 .801 -30 .492 1 .00 57 .26 C

ATOM 2654 CD LYS B 268 34 .047 56 .367 -30 .792 1 .00 65 .77 C

ATOM 2655 CE LYS B 268 32 .740 56 .892 -31 .429 1 .00 68 .62 C

ATOM 2656 NZ LYS B 268 32 .192 58 .057 -30 .638 1 .00 71 .31 N

ATOM 2657 C LYS B 268 35 .114 5 .178 -30 .992 1 .00 50 .03 C

ATOM 2658 O LYS B 268 34 .064 51. .563 -31 .066 1 .00 48 .13 O

ATOM 2659 N LEU B 269 36 .008 52 .220 -31 .996 1 .00 49 .06 N

ATOM 2660 CA LEU B 269 35 .866 51 .389 -33 .154 1 .00 49 .97 C

ATOM 2661 CB LEU B 269 37 .010 51 ,620 -34 .171 1 .00 48 .71 C

ATOM 2662 CG LEU B 269 36 ,9go 52 .985 -34 .961 1 .00 52 .44 C

ATOM 2663 CDl LEU B 269 38. .051 52, .973 -36, .139 1 .00 51 .70 C

ATOM 2664 CD2 LEU B 269 35, .578 53. ,415 -35 .493 1 .00 47 .05 C

ATOM 2665 C LEU B 269 35, .675 49. ,889 -32 .808 1 .00 51 .47 C

ATOM 2666 O LEU B 269 34, .881 49, .223 -33, .500 1. .00 51 .15 O

ATOM 2667 N ARG B 270 36, .389 49. .335 -31 .806 1 .00 50 .66 N

ATOM 2668 CA ARG B 270 36, ,2gι 47. .873 -31 .560 1 .00 50 .58 C

ATOM 2669 CB ARG B 270 37, .541 47. .298 -30, .874 1. .00 51. .47 C

ATOM 2670 CG ARG B 270 38, .770 47. ,630 -31, .759 1 .00 54 .02 C

ATOM 2671 CD ARG B 270 40, .107 46. .996 -31 .414 1 .00 58, .58 C

ATOM 2672 NE ARG B 270 40, .010 46, ,055 -30, .287 1. .00 59, .73 N

ATOM 2673 CZ ARG B 270 41, .094 45. ,569 -29, .651 1 .00 61, .77 C

ATOM 2674 NH1 ARG B 270 42, .315 45. .927 -30, .058 1. .00 55, .55 N

ATOM 2675 NH2 ARG B 270 40, .943 44, ,740 -28, .601 1. ,00 62. .35 N

ATOM 2676 C ARG B 270 34, .990 47. .547 -30, .883 1, .00 49. .39 C

ATOM 2677 O ARG B 270 34. .314 46. ,584 -31, .236 1, .00 49. .84 O

ATOM 2678 N ILE B 271 34 .560 48, .452 -30, .034 1, ,00 49. ,15 N

ATOM 2679 CA ILE B 271 33, .311 48, .366 -29, .319 1. ,00 48. .96 C

ATOM 2680 CB ILE B 271 33, .287 49. ,407 -28, .190 1. ,00 50. .01 C

ATOM 2681 CGI ILE B 271 34, .322 48. .967 -27, .056 1. ,00 49. .91 C

ATOM 2682 CDl ILE B 271 34, .773 50, .116 -26. .057 1. ,00 51. .70 C

ATOM 2683 CG2 ILE B 271 31. .850 49. ,629 -27. .644 1. .00 48. .74 C

ATOM 2684 C ILE B 271 32, .090 48. .462 -30, .191 1. ,00 51. .03 C

ATOM 2685 O ILE B 271 31, .159 47, .666 -30. ,025 1. ,00 52. .19 O

ATOM 2686 N GLU B 272 32, .090 49. .435 -31. .108 1, .00 50. .71 N

ATOM 2687 CA GLU B 272 31, ,094 49, .548 -32. .154 1. ,00 50. ,48 C

ATOM 2688 CB GLU B 272 31, .248 50, ,855 -32. .913 1. ,00 50. .08 C

ATOM 2689 CG GLU B 272 30. .921 52. .052 -32. ,033 1, .00 53. ,53 C

ATOM 2690 CD GLU B 272 31. .177 S3. .390 -32. .748 1, .00 58. ,75 C

ATOM 2691 OEl GLU B 272 31. .655 53. .390 -33, .926 1. ,00 56. ,15 O

ATOM 2692 OE2 GLU B 272 30. .860 54. .463 -32. ,128 1. .00 64. .80 O

ATOM 26g3 C GLU B 272 31. .080 48, .344 -33, .092 1, ,00 49. ,18 C

ATOM 2694 O GLU B 272 30, .040 47, .935 -33, .421 1. ,00 47. ,61 O

ATOM 2695 N LYS B 273 32, .216 47. .808 -33. ,523 1. ,00 51. ,00 N

ATOM 2696 CA LYS B 273 32, ,213 46. .563 -34. .274 1. ,00 55. ,28 C

ATOM 2697 CB LYS B 273 33. .581 45, .981 -34, .514 1. ,00 54. ,34 C

ATOM 2698 CG LYS B 273 33. ,796 45, .608 -35, ,954 1. ,00 58. .46 C

ATOM 2699 CD LYS B 273 34, .573 44, ,337 -36, .113 1, .00 63. ,83 C

ATOM 2700 CE LYS B 273 36, .050 44 .658 -36, .367 1. .00 68. ,76 C

ATOM 2701 NZ LYS B 273 36, .911 43, .429 -36, .121 1. ,00 73. ,20 N

ATOM 2702 C LYS B 273 31, .343 45, .502 -33. .545 1. ,00 57. .67 C

ATOM 2703 O LYS B 273 30, .402 44, .987 -34, .145 1, ,00 59. ,24 O

ATOM 2704 N ALA B 274 31 .586 45, .290 -32, .244 1. ,00 58. ,41 N

ATOM 2705 CA ALA B 274 30 .839 44, ,330 -31, .447 1. .00 58. .90 C

ATOM 2706 CB ALA B 274 31, .570 44, .017 -30, .078 1, .00 57. ,65 C

ATOM 2707 C ALA B 274 29 .387 4 .708 -31, .231 1. ,00 59. ,25 C

ATOM 2708 O ALA B 274 28 .547 43, .820 -31. ,137 1. .00 60. .63 O

ATOM 2709 N MET B 275 2g, ,054 45, .991 -31. .131 1, .00 59. ,30 N

ATOM 2710 CA MET B 275 27 .651 46 .348 -30, .932 1. ,00 60. .09 C

ATOM 2711 CB MET B 275 27 .466 47, .817 -30, ,633 1. .00 59, .12 C

ATOM 2712 CG MET B 275 27 .420 48. .156 -29, .188 1, ,00 65. .54 C

ATOM 2713 SD MET B 275 28 .038 49 .942 -28, .895 1. .00 76. ,29 S

ATOM 2714 CE MET B 275 26 .334 50 .927 -28, ,776 1. ,00 72, .08 C

ATOM 2715 C MET B 275 26 .842 46, .034 -32, .218 1, .00 59. .88 C

ATOM 2716 O MET B 275 25, ,630 45, .863 -32. ,166 1. ,00 59. 13 O

ATOM 2717 N LYS B 276 27, .539 46, .040 -33. .345 1. ,00 59. .84 N

ATOM 2718 CA LYS B 276 26, .936 46, .000 -34, .671 1. ,00 61, ,61 C

ATOM 2719 CB LYS B 276 27, .863 46, .642 -35. .713 1. ,00 61, ,18 C

ATOM 2720 CG LYS B 276 27 .392 46, .757 -37. .174 1. ,00 65. ,34 C

ATOM 2721 CD LYS B 276 28 ,691 46, .765 -38. .107 1. .00 70. ,11 C ATOM 2722 CE LYS B 276 28.425 46.451 -39.590 1.00 72.21 c

ATOM 2723 NZ LYS B 276 27.650 47.551 -40.232 1 .00 73 .31 N

ATOM 2724 C LYS B 276 26.72g 44.515 -34.941 1 .00 60 .43 C

ATOM 2725 O LYS B 276 25.700 44.157 -35.448 1 .00 59 .58 O

ATOM 2726 N GLU B 277 27.696 43.686 -34.565 1 .00 59. .37 N

ATOM 2727 CA GLU B 277 27.492 42.237 -34.529 1 .00 61 .07 C

ATOM 2728 CB GLU B 277 28.758 41.509 -34.228 1 .00 59 .99 C

ATOM 2729 CG GLU B 277 29.715 41.838 -35.325 1 .00 63. .77 C

ATOM 2730 CD GLU B 277 31.143 41.471 -34.997 1 .00 71, .62 C

ATOM 2731 OEl GLU B 277 31.440 41.058 -33.816 1 .00 71. .04 O

ATOM 2732 OE2 GLU B 277 31.963 41.619 -35.953 1 .00 73, ,71 O

ATOM 2733 C GLU B 277 26.381 41.853 -33.583 1 .00 60, .61 C

ATOM 2734 O GLU B 277 25.424 41.183 -33.968 1 .00 61 .01 O

ATOM 2735 N TYR B 278 26.415 42.373 -32.384 1 .00 60 .10 N

ATOM 2736 CA TYR B 278 25.269 42.106 -31.573 1 .00 60 .55 C

ATOM 2737 CB TYR B 278 25.360 42.800 -30.257 1 .00 59 .35 C

ATOM 2738 CG TYR B 278 24.113 42.796 -29.411 1 .00 61 .95 C

ATOM 2739 CDl TYR B 278 23.773 41.697 -28.606 1 .00 62 .84 C

ATOM 2740 CE1 TYR B 278 22.624 41.740 -27.780 1 .00 66 .53 C

ATOM 2741 CZ TYR B 278 21.824 42.913 -27.760 1 .00 69 .28 C

ATOM 2742 OH TYR B 278 20.689 43.016 -26.964 1 .00 69 .91 O

ATOM 2743 CE2 TYR B 278 22.162 44.022 -28.555 1 .00 65. .92 C

ATOM 2744 CD2 TYR B 278 23.291 43.952 -29.360 1 .00 65 . .g944 C

ATOM 2745 C TYR B 278 23.982 42.435 -32.312 1. .00 60, . .7722 C

ATOM 2746 O TYR B 278 23.032 41.679 -32.197 1 .00 61, .03 o

ATOM 2747 N GLU B 279 23.922 43.533 -33.066 1 .00 61. .54 N

ATOM 2748 CA GLU B 279 22.623 43.958 -33.576 1 .00 62. .23 C

ATOM 2749 CB GLU B 279 22.462 45.498 -33.692 1. .00 63. .3g C

ATOM 2750 CG GLU B 279 21.805 46.101 -32.425 1 .00 69. .96 C

ATOM 2751 CD GLU B 279 21.029 47.424 -32.627 1. .00 81. .28 C

ATOM 2752 OEl GLU B 279 21.668 48.522 -32.585 1. .00 85. .26 O

ATOM 2753 OE2 GLU B 279 19.763 47.388 -32.797 1, .00 84. .57 O

ATOM 2754 C GLU B 279 22.276 43.154 -34.850 1, .00 61. ,69 C

ATOM 2755 O GLU B 27g 21.135 42.996 -35.122 1 .00 58 .14 0

ATOM 2756 N GLU B 280 23.297 42.641 -35.567 1 .00 63 .24 N

ATOM 2757 CA GLU B 280 23.133 41.673 -36.628 1 .00 65 .83 C

ATOM 2758 CB GLU B 280 24.438 41.254 -37.288 1. .00 65 .35 C

ATOM 2759 CG GLU B 280 24.635 41.728 -38.742 1 .00 73 .21 C

ATOM 2760 CD GLU B 280 23.691 41.104 -39.857 1. .00 81, .34 C

ATOM 2761 OEl GLU B 280 23.150 39.942 -39.719 1 .00 77 .17 O

ATOM 2762 OE2 GLU B 280 23.489 41.816 -40.922 1. .00 81, .80 O

ATOM 2763 C GLU B 280 22.410 40.426 -36.060 1, ,00 66, .88 c

ATOM 2764 O GLU B 280 21.528 39.856 -36.750 1. .00 67, .54 o

ATOM 2765 N GLU B 281 22.711 40.029 -34.823 1, ,00 65, .85 N

ATOM 2766 CA GLU B 281 22.040 38.865 -34.346 1. .00 67. .11 C

ATOM 2767 CB GLU B 281 22.g09 37.891 -33.528 . 00 68 . 58 C

ATOM 2768 CG GLU B 281 23.810 37.045 -34.460 . 00 74 . 76 C

ATOM 2769 CD GLU B 281 23.706 35.503 -34.267 . 00 84 .44 c

ATOM 2770 OEl GLU B 281 22.567 34.924 -34.331 . 00 85 . 17 0

ATOM 2771 OE2 GLU B 281 24.790 34.850 -34.062 . 00 87 . 32 o

ATOM 2772 C GLU B 281 20.673 39.161 -33.79g . 00 66 . 19 c

ATOM 2773 O GLU B 281 19.772 38.360 -34.029 . 00 67 . 29 0

ATOM 2774 N GLU B 282 20.455 40.310 -33.175 . 00 64 . 33 N

ATOM 2775 CA GLU B 282 19.083 40.657 -32.814 . 00 63 . 97 C

ATOM 2776 CB GLU B 282 18.g80 42.045 -32.150 . 00 63 . 59 C

ATOM 2777 CG GLU B 282 19.155 42.119 -30.620 . 00 66 . 53 C

ATOM 2778 CD GLU B 282 19.257 40.742 -29.g02 . 00 69 . 32 C

ATOM 2779 OEl GLU B 282 18.333 40.389 -29.154 . 00 70 . 52 o

ATOM 2780 OE2 GLU B 282 20.265 40.004 -30.049 .00 69 .35 0

ATOM 2781 C GLU B 282 18.203 40.628 -34.077 . 00 63 . 94 c

ATOM 2782 O GLU B 282 16.981 40.406 -33.997 1 .00 64 .45 0

ATOM 2783 N ARG B 283 18.849 40.878 -35 . 217 1 .00 62 .81 N

ATOM 2784 CA ARG B 283 18.227 41.014 -36 . 496 1 .00 63 .32 C

ATOM 2785 CB ARG B 283 19.169 41.725 - 37 . 429 1 .00 63 .23 C

ATOM 2786 CG ARG B 283 18.528 42.280 -38 . 657 1 .00 66 .12 C

ATOM 2787 CD ARG B 283 19.410 42.260 -39 . 938 1 .00 70 .15 c

ATOM 2788 NE ARG B 283 18.449 42.455 -41 . 004 1 .00 74, .54 N

ATOM 2789 CZ ARG B 283 18.238 41.632 -42 . 035 1 .00 75 .69 C

ATOM 2790 NH1 ARG B 283 19.003 40.541 -42 . 234 1 .00 72 .16 N

ATOM 2791 NH2 ARG B 283 17.256 41.954 -42 . 890 1 .00 74, .07 N

ATOM 2792 C ARG B 283 17.905 39.618 -37 . 059 1 .00 62 .92 C

ATOM 2793 O ARG B 283 16.758 39.321 -37 . 265 1 .00 62, .41 O

ATOM 2794 N LYS B 284 18.916 38.788 -37 . 312 1 .00 63, .52 N

ATOM 2795 CA LYS B 284 18.746 37.337 -37 . 612 1 .00 6 .00 C

ATOM 2796 CB LYS B 284 20.057 36.578 -37 . 359 1 .00 63, .99 C

ATOM 2797 CG LYS B 284 21.225 36.995 -38 . 272 1, .00 64, .85 C

ATOM 2798 CD LYS B 284 22.194 35.832 -38 . 642 1 .00 73, .04 C ATOM 2799 CE LYS B 284 22.589 34.897 -37.451 1.00 76.38 c

ATOM 2800 NZ LYS B 284 21 .571 33 .797 -37 .082 1 .00 77 .18 N

ATOM 2801 C LYS B 284 17 .554 36 .641 -36 .868 1 .00 63 .76 C

ATOM 2802 O LYS B 284 16 .833 35 .863 -37 .478 1 .00 64 .60 O

ATOM 2803 N LYS B 285 17 .3ig 37 .032 -35 .606 1 .00 62 .75 N

ATOM 2804 CA LYS B 285 16 .408 36 .427 -34 .658 1 .00 61 .24 C

ATOM 2805 CB LYS B 285 16 ,g23 36 .741 -33 .253 1 .00 62 .27 C

ATOM 2806 CG LYS B 285 17 .g30 35 .712 -32 .672 1 .00 64 .86 C

ATOM 2807 CD LYS B 285 18 .559 36 .208 -31 .319 1 .00 67 .20 C

ATOM 2808 CE LYS B 285 17 .494 36 .671 -30 .2 6 1 .00 68 .36 C

ATOM 2809 NZ LYS B 285 18 .219 37 .190 -29 .075 1 .00 66 .43 N

ATOM 2810 C LYS B 285 15 .010 36 .944 -34 .660 1 .00 60 .42 C

ATOM 2811 O LYS B 285 14. .090 36 .324 -34 .093 1 .00 60 .97 O

ATOM 2812 N ARG B 286 14 .800 38 .136 -35 .163 1 .00 58 .58 N

ATOM 2813 CA ARG B 286 13 .403 38 .481 -35 .394 1 .00 56 .19 C

ATOM 2814 CB ARG B 286 13 .058 39 .895 -34 .845 1 .00 58 .38 C

ATOM 2815 CG ARG B 286 13 .926 41 .046 -35 .399 1 .00 59 .33 C

ATOM 2816 CD ARG B 286 13 .346 42 .465 -35 .221 1 .00 60 .66 C

ATOM 2817 NE ARG B 286 13, .954 43 .274 -36 .261 1 .00 63 .54 N

ATOM 2818 CZ ARG B 286 15 .149 43 .895 -36 .179 1 .00 64 .72 C

ATOM 2819 NH1 ARG B 286 15, .866 43 .883 -35 .048 1 .00 64 .92 N

ATOM 2820 NH2 ARG B 286 15, .610 44. .570 -37. .237 1. .00 61 .74 N

ATOM 2821 C ARG B 286 12, .972 38 .263 -36 .894 1 .00 52 .67 C

ATOM 2822 O ARG B 286 11, .853 38, .563 -37 .250 1. .00 53 .20 O

ATOM 2823 N LEU B 287 13. .856 37, .766 -37 .745 1 .00 47 .g4 N

ATOM 2824 CA LEU B 287 13. .496 37, .428 -39, .082 1, .00 46 .85 C

ATOM 2825 CB LEU B 287 14, .683 36 .715 -39 .779 1 .00 47 .55 C

ATOM 2826 CG LEU B 287 15, .885 37, .588 -40. .231 1, .00 46 .36 C

ATOM 2827 CDl LEU B 287 16, .892 36 .749 -41 .029 1 .00 41 .19 C

ATOM 2828 CD2 LEU B 287 15, .424 38, .823 -41, .061 1, .00 45, .67 C

ATOM 2829 C LEU B 287 12, .284 36 .457 -39 .118 1, .00 45 .47 C

ATOM 2830 O LEU B 287 12, .229 35, .470 -38, .388 1, .00 44, ,00 O

ATOM 2831 N GLY B 288 11. .351 36 .774 -39 .988 1, .00 44 .59 N

ATOM 2832 CA GLY B 288 10, .283 35, .885 -40, .403 1, .00 42, .42 C

ATOM 2833 C GLY B 288 10. .621 34, .506 -40 .969 1, .00 40. .73 C

ATOM 2834 0 GLY B 288 11, .786 34, .143 -41, .176 1, .00 39, .24 O

ATOM 2835 N PRO B 289 9, .561 33 .686 -41 .198 1, .00 40, .77 N

ATOM 2836 CA PRO B 289 9, ,778 32, .271 -41, .639 1, .00 37, .72 C

ATOM 2837 CB PRO B 289 8, .357 31 .615 -41, .533 1, .00 37, .50 C

ATOM 2838 CG PRO B 289 7, ,334 32, .798 -41, .558 1. .00 38, .80 C

ATOM 2839 CD PRO B 289 8, ,143 34, .027 -40. .937 1. .00 37. ,36 C

ATOM 2840 C PRO B 289 10, .379 32, .208 -43. .037 1. .00 37, ,40 C

ATOM 2841 O PRO B 289 11. ,045 31. .223 -43. .449 1. ,00 37. ,99 O

ATOM 2842 N GLY B 290 10, .091 33, .257 -43, .7gι 1, ,00 36, .58 N

ATOM 2843 CA GLY B 290 10. ,606 33. .401 -45, .121 1. ,00 38. ,40 C

ATOM 2844 C GLY B 290 11. .903 34. .279 -45, .147 1. .00 40, ,56 C

ATOM 2845 O GLY B 290 12, .274 34, .680 -46. .224 1. ,00 39. .31 o

ATOM 2846 N GLY B 291 12, .583 34, .460 -43. .993 1. .00 41. .34 N

ATOM 2847 CA GLY B 291 13, .785 35, .256 -43, .834 1, ,00 43. ,83 C

ATOM 2848 C GLY B 291 13. .641 36, .794 -43, .942 1, .00 45, .95 C

ATOM 2849 O GLY B 291 14. .631 37, .440 -44, .084 1, .00 46. .66 O

ATOM 2850 N LEU B 292 12, .436 37 .354 -43, .888 1, .00 46. .95 N

ATOM 2851 CA LEU B 292 12. .230 38, .807 -43, .906 1. .00 48. .83 C

ATOM 2852 CB LEU B 292 11. .045 3g, .254 -44, .804 1. .00 48. .53 C

ATOM 2853 CG LEU B 292 11, .202 38, .843 -46, .292 1. ,00 49. .84 C

ATOM 2854 CDl LEU B 292 10, .190 39 .463 -47, .173 1. .00 46. .72 C

ATOM 2855 CD2 LEU B 292 12, .663 38, .876 -46, .953 1. ,00 50. ,08 C

ATOM 2856 C LEU B 292 12, ,023 39, .368 -42, .516 1. ,00 50. ,52 C

ATOM 2857 O LEU B 292 11, .438 38, .707 -41, .603 1. ,00 50. ,30 0

ATOM 2858 N ASP B 293 12, ,547 40, .588 -42, ,343 1. 00 53. ,22 N

ATOM 2859 CA ASP B 293 12, ,408 41, .386 -41, .096 1. ,00 53. ,13 C

ATOM 2860 CB ASP B 293 13, ,471 42. ,481 -41, ,043 1. ,00 55. ,48 C

ATOM 2861 CG ASP B 293 13, ,628 43. .098 -39, .619 1. ,00 59. ,28 C

ATOM 2862 OD1 ASP B 293 12, ,592 43, .374 -38. .915 1. ,00 59. ,80 O

ATOM 2863 OD2 ASP B 293 14, .772 43, .342 -39, .164 1. ,00 62. ,39 O

ATOM 2864 C ASP B 293 11, .062 42, .054 -41. .132 1. 00 50. ,95 C

ATOM 2865 O ASP B 293 10, .741 42 .745 -42, .115 1. ,00 51. ,15 O

ATOM 2866 N PRO B 294 10, .224 41, .811 -40. .131 1. ,00 49. ,46 N

ATOM 2867 CA PRO B 294 8 .920 42 .497 -40, .130 1. ,00 49. ,67 C

ATOM 2868 CB PRO B 294 8, .099 41, .698 -39, .131 1. ,00 47. .32 C

ATOM 2869 CG PRO B 294 9 .143 41 .190 -38, .102 1. ,00 46. .83 C

ATOM 2870 CD PRO B 294 10, .423 40, .927 -38, .951 1. ,00 47. ,56 C

ATOM 2871 C PRO B 294 9 .006 44 .057 -39, .760 1, ,00 52. .00 C

ATOM 2872 O PRO B 294 8, .011 44, .779 -40, .031 1. ,00 50. ,28 O

ATOM 2873 N VAL B 295 10 .140 44 .544 -39, .180 1. .00 54, .70 N

ATOM 2874 CA VAL B 295 10 .360 46 .037 -38, .988 1. .00 56. .91 C

ATOM 2875 CB VAL B 295 11 .619 46 .389 -38. .101 1, ,00 57. .49 C ATOM 2876 CGI VAL B 295 12.141 47.867 -38.314 1.00 57.69 c

ATOM 2877 CG2 VAL B 295 11 .380 46 .032 -36 .612 1 .00 57 .64 c

ATOM 2878 C VAL B 295 10 .468 46 .654 -40 .381 1 .00 58 .19 c

ATOM 2879 O VAL B 295 9 .623 47 .516 -40 .735 1 .00 58 .91 o

ATOM 2880 N GLU B 296 11 .430 46 .162 -41 .195 1 .00 57 .86 N

ATOM 2881 CA GLU B 296 11 .561 46 .637 -42 .586 1 .00 60 .32 C

ATOM 2882 CB GLU B 296 12 .752 45 . 73 -43 .349 1 .00 60 .49 C

ATOM 2883 CG GLU B 296 13 .884 45 .577 -42 .400 1 .00 68 .23 c

ATOM 2884 CD GLU B 296 15 .212 45 .270 -43 .110 1 .00 76 .49 c

ATOM 2885 OEl GLU B 296 15 .207 45 .341 -44 .384 1 .00 76 .71 0

ATOM 2886 OE2 GLU B 296 16 .228 44 .g 0 -42 .394 1 .00 76 .40 o

ATOM 2887 C GLU B 2g6 10 .286 46 .5og -43 .400 1 .00 60 .33 c

ATOM 2888 O GLU B 296 9 .856 47 .475 -44 .090 1 .00 60 .42 o

ATOM 2889 N VAL B 297 9 .675 45 .306 -43 .340 1 .00 60 .17 N

ATOM 2890 CA VAL B 297 8 .517 45 .047 -44 .199 1 .00 58 .28 C

ATOM 2891 CB VAL B 297 7 .998 43 .475 -44 .260 1 .00 58 .05 c

ATOM 2892 CGI VAL B 297 6 .553 43 .338 -45 .004 1 .00 53 .01 c

ATOM 2893 CG2 VAL B 297 9 .023 42 .604 -44 .920 1 .00 53 .05 c

ATOM 2894 C VAL B 297 7 .427 46 .006 -43 .789 1 .00 58 .93 c

ATOM 2895 O VAL B 297 6 .781 46 .521 -44 .652 1 .00 58 .08 o

ATOM 2896 N TYR B 298 7 .201 46 .207 -42 .491 1 .00 61 .39 N

ATOM 2897 CA TYR B 2g8 6 .215 47 .211 -42 .034 1 .00 65 .44 C

ATOM 2898 CB TYR B 298 6 .246 47 .387 -40 .497 1. .00 65 .34 C

ATOM 289g CG TYR B 298 5 .245 48 .418 -39 .981 1 .00 71 .24 C

ATOM 2goo CDl TYR B 298 3. .866 48 .26g -40 .247 1. .00 75 .06 C

ATOM 2901 CE1 TYR B 298 2 .919 49 .203 -39 .798 1. .00 78 .10 C

ATOM 2902 CZ TYR B 298 3. .339 50 .317 -39 .044 1 .00 79 .80 c

ATOM 2903 OH TYR B 298 2 .356 51 .186 -38 .600 1. .00 81. .70 o

ATOM 2904 CE2 TYR B 298 4 .721 50 .503 -38 .745 1 .00 75 .77 c

ATOM 2905 CD2 TYR B 298 5 .660 49 .546 -39 .214 1. .00 74. .09 c

ATOM 2906 C TYR B 298 6 .378 48 .612 -42 .738 1 .00 66 .94 c

ATOM 2907 O TYR B 298 5, .373 49 .230 -43 .211 1. .00 65. .26 o

ATOM 2908 N GLU B 299 7. .644 49 .060 -42 .800 1 .00 68, .84 N

ATOM 2909 CA GLU B 299 8, .006 50 .404 -43 .240 1, .00 71, .46 C

ATOM 2910 CB GLU B 299 9 .485 50 .775 -42 .863 1. .00 72, .07 C

ATOM 2911 CG GLU B 299 9 .962 50, .784 -41 .357 1, .00 74. .24 c

ATOM 2912 CD GLU B 299 9 .024 51. .498 -40 .341 1, .00 79. .81 c

ATOM 2913 OEl GLU B 299 7, .919 52, .001 -40, .732 1, .00 82. .63 o

ATOM 2914 OE2 GLU B 299 9 .372 51 .564 -39 .130 1, .00 78. ,74 o

ATOM 2915 C GLU B 299 7, .791 50, .537 -44, .753 1. .00 73. ,22 c

ATOM 2916 O GLU B 299 7 .457 51 .643 -45 .272 1, .00 74, .07 o

ATOM 2917 N SER B 300 7, .992 49, .423 -45, .469 1. .00 74. .58 N

ATOM 2918 CA SER B 300 7. ,890 49, .384 -46, .935 1. .00 75. ,97 C

ATOM 2919 CB SER B 300 8, ,633 48, .172 -47, .471 1. ,00 76. ,23 C

ATOM 2920 OG SER B 300 7. ,971 46. .992 -47. .020 1. ,00 77. ,54 O

ATOM 2921 C SER B 300 6, ,442 49, .328 -47, .405 1. .00 76. ,83 c

ATOM 2922 O SER B 300 6. .169 49, .484 -48. .598 1. .00 76. ,93 o

ATOM 2923 N LEU B 301 5, .533 49, .117 -46. .455 1. .00 78. ,53 N

ATOM 2924 CA LEU B 301 4. ,101 48, .974 -46. .704 1. .00 81. .44 C

ATOM 2925 CB LEU B 301 3. .461 48, .344 -45. .456 1. ,00 80. ,62 C

ATOM 2926 CG LEU B 301 3. ,529 46, .840 -45, .158 1. ,00 79. ,06 C

ATOM 2927 CDl LEU B 301 2, .720 46, .537 -43, .945 1. .00 74. ,24 C

ATOM 2928 CD2 LEU B 301 3. .064 45. .966 -46, .341 1. .00 76. ,83 C

ATOM 2929 C LEU B 301 3, ,374 50. .307 -46, .951 1. ,00 84. ,46 c

ATOM 2930 O LEU B 301 3. ,628 51, .244 -46, .180 1. ,00 85. ,14 0

ATOM 2931 N PRO B 302 2, .454 50, .411 -47, .939 1. ,00 87. .00 N

ATOM 2932 CA PRO B 302 1. ,549 51, .568 -48, .011 1. ,00 88. ,85 C

ATOM 2933 CB PRO B 302 0, ,433 51, .091 -48, .957 1. ,00 88. ,12 C

ATOM 2934 CG PRO B 302 1. ,148 50. .280 -49, .923 1. ,00 87. ,67 C

ATOM 2935 CD PRO B 302 2, ,206 4g. .5ig -49, .093 1. ,00 87. ,64 C

ATOM 2936 C PRO B 302 1. ,003 52. .006 -46, .632 1. ,00 90. ,93 C

ATOM 2937 O PRO B 302 0. ,856 51. ,193 -45. ,675 1. ,00 90. ,27 o

ATOM 2938 N GLU B 303 0. ,773 53. .322 -46, .540 1. ,00 93. ,05 N

ATOM 2939 CA GLU B 303 0. ,277 53. .927 -45. ,321 1. 00 95. 12 C

ATOM 2940 CB GLU B 303 0. ,084 55, ,457 -45, .471 1. ,00 gs. ,68 C

ATOM 2941 CG GLU B 303 0. 653 56. ,112 -46, .754 1. 00 gβ. 67 C

ATOM 2942 CD GLU B 303 -0, .071 57, .421 -47, .182 1. ,00101. ,34 C

ATOM 2943 OEl GLU B 303 -1. ,104 57. ,792 -46, ,560 1. 00100. 76 O

ATOM ₂944 OE2 GLU B 303 0, ,387 58, .086 -48, .157 1. .00101. ,42 O

ATOM 2945 C GLU B 303 -1. ,050 53. .215 -45, ,115 1. 00 gs. 74 c

ATOM 2946 O GLU B 303 -1. ,744 52. .905 -46, ,097 1. ,00 95. ,60 o

ATOM 2947 N GLU B 304 -1. ,360 52, ,92g -43, ,853 1. 00 96. 51 N

ATOM 2948 CA GLU B 304 -2, ,652 52. .396 -43, .390 1. ,00 97. ,58 C

ATOM 2949 CB GLU B 304 -3. ,411 51. ,576 -44, .467 1. 00 97. 64 C

ATOM 2950 CG GLU B 304 -4, ,273 52. .349 -45, .467 1. 00 99. 59 C

ATOM 2951 CD GLU B 304 -4. ,219 51. ,751 -46, ,873 1. 00100. 99 C

ATOM 2952 OEl GLU B 304 -3, ,104 51, .445 -47, .374 1. 00100. 87 o ATOM 2953 OE2 GLU B 304 -5.300 51.594 -47.485 1.00100.59 0

ATOM 2954 C GLU B 304 -2 .282 "51 .439 -42 .286 1 .00 97 .68 c

ATOM 2955 O GLU B 304 -2 .924 51 .352 -41 .22g 1 .00 97 .48 0

ATOM 2956 N LEU B 305 -1 .207 50 .716 -42 .551 1 .00 98 .01 N

ATOM 2957 CA LEU B 305 -1 .308 49 .332 -42 .227 1 .00 98 .22 C

ATOM 2958 CB LEU B 305 -0 .789 48 .410 -43 .343 1 .00 97 .51 C

ATOM 295g CG LEU B 305 -1 .515 48 .598 -44 .708 1 .00 96 .53 C

ATOM 2 εo CDl LEU B 305 -1 .177 47 .556 -45 .812 1 .00 94 .43 C

ATOM 2961 CD2 LEU B 305 -3 .038 48 .745 -44 .583 1 .00 96 .64 C

ATOM 2962 C LEU B 305 -1 .03g 49 .003 -40 .760 1 .00 99 .41 C

ATOM 2963 O LEU B 305 -0 .292 49 .716 -40 .043 1 .00 98 .85 o

ATOM 2964 N GLN B 306 -1 .729 47 .931 -40 .351 1 .00100 .67 N

ATOM 2965 CA GLN B 306 -2 .420 47 .820 -39 .064 1 .00101 .34 C

ATOM 2966 CB GLN B 306 -3 .379 46 .606 -39 .101 1 .00100 .83 C

ATOM 2967 CG GLN B 306 -4 .763 46 .846 -39 .761 1 .oo gs .62 C

ATOM 2968 CD GLN B 306 -4 .773 47 .769 -41 .025 1 .00 gs .97 C

ATOM 2969 OEl GLN B 306 -5 136 47 .332 -42 .149 1 .oo go .32 O

ATOM 2970 NE2 GLN B 306 -4 .442 49 .056 -40 .820 1 .00 93 .84 N

ATOM 2971 C GLN B 306 -1 590 47 .846 -37 .768 1 .00102 .46 C

ATOM 2972 O GLN B 306 -1 354 46 .782 -37 .161 1 .00101 94 O

ATOM 2973 N LYS B 307 -1 187 49 063 -37 .342 1 00103 70 N

ATOM 2974 CA LYS B 307 -0 886 49 323 -35 922 1 00104 74 C

ATOM 2975 CB LYS B 307 -0 710 50 825 -35 .614 1 00105 08 C

ATOM 2976 CG LYS B 307 0 713 51 407 -35 796 1 00106 87 C

ATOM 2977 CD LYS B 307 0 734 52 968 -35 659 1 00107 79 C

ATOM 2g78 CE LYS B 307 0 610 53 εgg -37 028 1 00110 18 C

ATOM 2g79 NZ LYS B 307 -0 374 53 070 -38 021 1 00109 2 N

ATOM 2980 C LYS B 307 -2 091 48 746 -35 138 1 00104 eg C

ATOM 2981 O LYS B 307 -2 006 48 486 -33 933 1 00105 57 O

ATOM 2982 N CYS B 308 -3 210 48 563 -35 846 1 00104 62 N

ATOM 2983 CA CYS B 308 -4 346 47 772 -35 386 1 00104 58 C

ATOM 2984 CB CYS B 308 -3 935 46 743 -34 332 1 00104 65 C

ATOM 2985 SG CYS B 308 -4 758 45 171 -34 592 1 00105 08 S

ATOM 2986 C CYS B 308 -5 47g 48 622 -34 849 1 00104 53 C

ATOM 2987 O CYS B 308 -6 562 48 105 -34 602 1 00103 89 O

ATOM 2988 N MET B 316 -7 959 43 604 -39 192 1 00125 66 N

ATOM 298g CA MET B 316 -8 310 42 195 -39 386 1 00126 52 C

ATOM 2 90 CB MET B 316 -8 832 41 578 -38 073 1 00127 04 C

ATOM 29gi CG MET B 316 -7 949 40 432 -37 485 1 00128 76 C

ATOM 2 92 SD MET B 316 -7 958 40 282 -35 628 1 00132 61 S

ATOM 2993 CE MET B 316 -7 479 38 424 -35 323 1 00130 32 C

ATOM 29 4 C MET B 316 -9 231 41 953 -40 629 1 00126 39 C

ATOM 2995 0 MET B 316 -8 736 42 056 -41 742 1 00126 22 O

ATOM 29 6 N LEU B 317 10 532 41 639 -40 4 2 1 00126 sg N

ATOM 2997 CA LEU B 317 11 405 41 572 -41 707 1 00126 56 C

ATOM 2998 CB LEU B 317 12 544 40 502 -41 677 1 00126 22 C

ATOM 2999 CG LEU B 317 13 112 40 149 -43 087 1 00125 11 C

ATOM 3000 CDl LEU B 317 12 704 38 747 -43 595 1 00123 70 C

ATOM 3001 CD2 LEU B 317 14 638 40 412 -43 226 1 00122 75 C

ATOM 3002 C LEU B 317 11 944 42 948 -42 122 1 00126 65 C

ATOM 3003 O LEU B 317 12 763 43 054 -43 051 1 00126 83 O

ATOM 3004 N GLN B 318 11 486 43 995 -41 434 1 00126 56 N

ATOM 3005 CA GLN B 318 11 739 45 345 -41 o7 1 00126 47 C

ATOM 3006 CB GLN B 318 11 538 46 412 -40 813 1 00126 62 C

ATOM 3007 CG GLN B 318 12 036 47 845 -41 198 1 00125 82 C

ATOM 3008 CD GLN B 318 13 446 47 877 -41 824 1 00124 28 C

ATOM 3009 OEl GLN B 318 13 633 47 514 -42 995 1 00122 96 O

ATOM 3010 NE2 GLN B 318 14 429 48 323 -41 044 1 00123 54 N

ATOM 3011 C GLN B 318 10 759 45 536 -43 034 1 00126 31 C

ATOM 3012 O GLN B 318 11 131 45 609 -44 216 1 00126 31 O

ATOM 3013 N ASP B 319 -9 4g7 45 587 -42 650 1 00125 99 N

ATOM 3014 CA ASP B 319 -8 413 45 581 -43 599 1 00125 96 C

ATOM 3015 CB ASP B 319 -7 146 45 292 -42 814 1 00126 00 C

ATOM 3016 CG ASP B 319 -6 147 44 519 -43 611 1 00126 66 C

ATOM 3017 OD1 ASP B 319 -5 730 45 025 -44 665 1 00127 88 O

ATOM 3018 OD2 ASP B 319 -5 726 43 394 -43 285 1 00126 98 O

ATOM 3019 C ASP B 319 -8 585 44 615 -44 834 1 00125 83 C

ATOM 3020 O ASP B 319 -8 195 44 980 -45 94g 1 00125 85 O

ATOM 3021 N ALA B 320 -9 152 43 408 -44 643 1 00125 43 N

ATOM 3022 CA ALA B 320 -9 372 42 441 -45 752 1 00124 84 C

ATOM 3023 CB ALA B 320 10 073 41 144 -45 262 1 00124 82 C

ATOM 3024 C ALA B 320 10 141 43 053 -46 926 1 00124 55 C

ATOM 3025 O ALA B 320 -9 685 42 968 -48 066 1 00124 12 O

ATOM 3026 N ILE B 321 11 292 43 684 -46 627 1 00124 43 N

ATOM 3027 CA ILE B 321 12 138 44 390 -47 628 1 00123 85 C

ATOM 3028 CB ILE B 321 13 672 44 643 -47 105 1 00123 88 C

ATOM 3029 CGI ILE B 321 14 722 44 062 -48 122 1 00123 23 C ATOM 3030 CDl ILE B 321 -16.201 44.617 -47.998 1.00120.91 C

ATOM 3031 CG2 ILE B 321 -13 .907 46 .108 -46 .583 1 .00123 .23 C

ATOM 3032 C ILE B 321 -11 .401 45 .618 -48 .249 1 .00123 .33 C

ATOM 3033 0 ILE B 321 -11 .888 46 .249 -49 .194 1 .00123 .35 O

ATOM 3034 N SER B 322 -10 .203 45 .900 -47 .734 1 .00122 .20 N

ATOM 3035 CA SER B 322 -9 .207 46 .684 -48 .450 1 .00121 .10 C

ATOM 3036 CB SER B 322 -8 .281 47 .356 -47 .436 1 .00120 .93 C

ATOM 3037 OG SER B 322 -7 .138 47 .880 -48 .066 1 .00119 .55 O

ATOM 3038 C SER B 322 -8 .428 45 .840 -49 .514 1 .00120 .89 c

ATOM 3039 0 SER B 322 -7 .232 46 .045 -4g .735 1 .00120 .33 0

ATOM 3040 N LYS B 323 -9 .116 44 .883 -50 .152 1 .00120 .61 N

ATOM 3041 CA LYS B 323 -8 .680 44 .293 -51 .432 1 .00120 .32 C

ATOM 3042 CB LYS B 323 -9 .447 42 .996 -51 .774 1 .00120 .32 C

ATOM 3043 CG LYS B 323 -8 .692 41 .998 -52 .698 1 .00119 .62 C

ATOM 3044 CD LYS B 323 -9 .191 40 .532 -52 .564 1 .00118 .70 C

ATOM 3045 CE LYS B 323 -8 .073 39 .491 -52 .854 1 .00117 .73 C

ATOM 3046 NZ LYS B 323 -8 .521 38 .059 -52 .707 1 .00115 .78 N

ATOM 3047 C LYS B 323 -8 .901 45 .371 -52 .508 1 .00120 .44 C

ATOM 3048 0 LYS B 323 -10 .009 45 .566 -53 .032 1 .00120 .11 O

ATOM 3049 N MET B 324 -7 .816 46 .064 -52 .840 1 .00120 .25 N

ATOM 3050 CA MET B 324 -7 .g24 47 .447 -53 .268 1 .00119 .81 C

ATOM 3051 CB MET B 324 -7 .884 48 .296 -51 .992 1 .00120 .48 C

ATOM 3052 CG MET B 324 -9 .169 48 .993 -51 .666 1 .00122 .14 C

ATOM 3053 SD MET B 324 -8 .965 50 .767 -52 .046 1 .00127 .15 S

ATOM 3054 CE MET B 324 -7 .211 51 .176 -51 .384 1 .00124 .27 C

ATOM 3055 C MET B 324 -6 .821 47 .942 -54 .209 1 .00118 .72 C

ATOM 3056 0 MET B 324 -6 .558 49 .156 -54 .252 1 .00119 .12 O

ATOM 3057 N ASP B 325 -6 .172 47 .032 -54 .941 1 .00116 .80 N

ATOM 3058 CA ASP B 325 -5 .033 47 .379 -55 .814 1 .00115 .21 C

ATOM 3059 CB ASP B 325 -3, .841 48 .010 -55 .034 1 .00115 .40 C

ATOM 3060 CG ASP B 325 -3 .488 47 .261 -53 .724 1 .00117 .02 C

ATOM 3061 OD1 ASP B 325 -4, .405 46 .955 -52 .923 1 .00119 .47 O

ATOM 3062 OD2 ASP B 325 -2, .312 46 .960 -53. .391 1 .00115. .99 O

ATOM 3063 C ASP B 325 -4, .607 46 .148 -56 .611 1 .00113 .69 C

ATOM 3064 0 ASP B 325 -4. .919 45 .038 -56, .173 1 .00113. .60 O

ATOM 3065 N PRO B 326 -3, .876 46 .328 -57, .735 1 .00112 .25 N

ATOM 3066 CA PRO B 326 -3. ,784 45 .295 -58, .812 1 .00110. .eg C

ATOM 3067 CB PRO B 326 -2, .942 45 .987 -59 .904 1 .00110. .77 C

ATOM 3068 CG PRO B 326 -2. ,150 47, .063 -59, .159 1, .00111. .43 C

ATOM 3069 CD PRO B 326 -3, ,043 47 .517 -58, .038 1, .00111 .77 C

ATOM 3070 C PRO B 326 -3. ,193 43, .897 -58, .431 1. ,00109, .59 C

ATOM 3071 0 PRO B 326 -3. ,924 43 .042 -57, .905 1 .00109, .66 O

ATOM 3072 N THR B 327 -1. 910 43. .674 -58, .745 1, .00107, ,58 N

ATOM 3073 CA THR B 327 -1. ,116 42, .524 -58, .288 1. .00104. .84 C

ATOM 3074 CB THR B 327 -0. 373 41, .840 -59, .469 1, .00105. .20 C

ATOM 3075 OG1 THR B 327 0. ,600 42, .748 -60, .026 1. .00104. .32 O

ATOM 3076 CG2 THR B 327 -1. .316 41, .498 -60, ,639 1. .00104. .83 C

ATOM 3077 C THR B 327 -0. ,067 43, .045 -57, .299 1, .00103, .20 C

ATOM 3078 0 THR B 327 0. 718 42, .287 -56. .725 1. ,00103, ,11 0

ATOM 3079 N ASP B 328 -0. 033 44, .358 -57, .134 1. .00100. .59 N

ATOM 3080 CA ASP B 328 0. 756 44. ,960 -56. ,083 1. ,00 98. ,22 C

ATOM 3081 CB ASP B 328 0. 643 46, .517 -56, .113 1. .00 98, .82 C

ATOM 3082 CG ASP B 328 1. 783 47. ,186 -56. ,955 1. .00100. ,78 C

ATOM 3083 OD1 ASP B 328 2. 977 46. ,885 -56, .688 1. ,00102, ,45 O

ATOM 3084 OD2 ASP B 328 1. 597 48. ,004 -57. ,903 1. ,00100. ,60 O

ATOM 3085 C ASP B 328 0. 347 44. ,353 -54. ,728 1. ,00 95. ,65 C

ATOM 3086 0 ASP B 328 1. 159 44. ,309 -53. ,806 1. 00 95. ,03 O

ATOM 3087 N ALA B 329 -0. 891 43. ,854 -54. ,629 1. ,00 92. ,71 N

ATOM 3088 CA ALA B 329 -1. 380 43. ,210 -53. ,400 1. 00 90. 01 C

ATOM 3089 CB ALA B 329 -2. 917 43. .107 -53. ,400 1. 00 89. ,66 C

ATOM 3090 C ALA B 329 -0. 702 41. ,837 -53. 070 1. 00 88. 08 C

ATOM 3091 0 ALA B 329 -0. 342 41. ,587 -51. ,913 1. 00 87. ,42 O

ATOM 3092 N LYS B 330 -0. 518 40. ,973 -54. .082 1. 00 85. 87 N

ATOM 3093 CA LYS B 330 0. 243 3g. ,713 -53. ,935 1. 00 83. ,48 C

ATOM 3094 CB LYS B 330 0. 189 38. 838 -55. 219 1. 00 84. 74 C

ATOM 3095 CG LYS B 330 -1. 204 38. ,110 -55. ,474 1. 00 89. ,28 C

ATOM 3096 CD LYS B 330 -1. 227 37. 104 -56. ,655 1. 00 93. 38 C

ATOM 3097 CE LYS B 330 -1. 377 35. ,665 -56. ,138 1. 00 95. ,96 C

ATOM 3098 NZ LYS B 330 -0. 015 35. ,053 -55. 912 1. oo gs. 56 N

ATOM 30g9 C LYS B 330 1. 695 40. ,004 -53. ,524 1. 00 80. ,31 C

ATOM 3100 0 LYS B 330 2. 328 39. 210 -52. ,850 1. 00 80. 22 O

ATOM 3101 N TYR B 331 2. 195 41. ,173 -53. ,go7 1. 00 76. ,24 N

ATOM 3102 CA TYR B 331 3. 561 41. 580 -53. 607 1. 00 71. 56 C

ATOM 3103 CB TYR B 331 4. 053 42. ,660 -54. .600 1. 00 70. ,45 C

ATOM 3104 CG TYR B 331 5. 372 43. 271 -54. 191 1. 00 68. 22 C

ATOM 3105 CDl TYR B 331 6. 597 42. ,803 -54. .713 1. 00 64. ,38 C

ATOM 3106 CE1 TYR B 331 7. 806 43. 372 -54. 312 1. 00 63. 22 C ATOM 3107 CZ TYR B 331 7.803 44.432 -53.354 1.00 66.61 c

ATOM 3108 OH TYR B 331 8 .970 45 .064 -52 .882 1 .00 63 .26 o

ATOM 3iog CE2 TYR B 331 6 .585 44 .885 -52 .816 1 .00 66 .78 c

ATOM 3110 CD2 TYR B 331 5 .3g5 44 .317 -53 .245 1 .00 66 .36 c

ATOM 3111 C TYR B 331 3 .801 41 .976 -52 .123 1 .00 eg .30 c

ATOM 3112 O TYR B 331 4 .782 41 .561 -51 .519 1 .00 68 .72 o

ATOM 3113 N HIS B 332 2 .930 42 .783 -51 .543 1 .00 67 .04 N

ATOM 3114 CA HIS B 332 3 .103 43 .152 -50 .150 1 .00 65 .21 C

ATOM 3115 CB HIS B 332 2 .336 44 .43g -49 .768 1 .00 66 .76 C

ATOM 3116 CG HIS B 332 2 .897 45 .eg6 -50 .367 1 .00 71 .56 C

ATOM 3117 ND1 HIS B 332 4 .088 46 .255 -49 .944 1 .00 74 .33 N

ATOM 3118 CE1 HIS B 332 4 .322 47 .347 -50 .657 1 .00 77 .24 C

ATOM 3119 NE2 HIS B 332 3 .328 47 .515 -51 .518 1 .00 75 .90 N

ATOM 3120 CD2 HIS B 332 2 .420 46 .504 -51 .351 1 .00 73 .57 C

ATOM 3121 C HIS B 332 2 .603 42 .054 -4g .240 1 .00 62 .31 C

ATOM 3122 O HIS B 332 3 .152 41 .βg3 -48 .138 1 .00 62 .56 O

ATOM 3123 N MET B 333 1 .522 41 .367 -4g .651 1 .00 58 .51 N

ATOM 3124 CA MET B 333 0 .973 40 .258 -48 .846 1 .00 55 .83 C

ATOM 3125 CB MET B 333 -0 .329 39 .658 -49 .442 1 .00 57 .53 C

ATOM 3126 CG MET B 333 -1 .594 40 .306 -48 .957 1 .00 64 .10 C

ATOM 3127 SD MET B 333 -1 .459 40 .gn -47 .150 1 .00 77 .77 S

ATOM 3128 CE MET B 333 -0 .815 42, .610 -47 .502 1 .00 75 .09 C

ATOM 3129 C MET B 333 2 .061 39 .178 -48 .732 1 .00 50 .65 C

ATOM 3130 O MET B 333 2 .348 38 .778 -47 .646 1 .00 49 .78 O

ATOM 3131 N GLN B 334 2 .690 38 .797 -49 .842 1 .00 45 .31 N

ATOM 3132 CA GLN B 334 3 .768 37, .834 -49 .776 1 .00 43 .91 C

ATOM 3133 CB GLN B 334 4 .363 37 .539 -51 .136 1 .00 40 .36 C

ATOM 3134 CG GLN B 334 5 .356 36 .423 -51 .080 1 .00 39 .82 C

ATOM 3135 CD GLN B 334 4 .731 35, .075 -50 .530 1 .00 40, .63 C

ATOM 3136 OEl GLN B 334 3 .611 34, .687 -50 .948 1. .00 40, .93 O

ATOM 3137 NE2 GLN B 334 5 .384 34 .454 -49 .549 1 .00 34, .81 N

ATOM 3138 C GLN B 334 4 .866 38 .i9g -48 .732 1 .00 44. .69 C

ATOM 3139 O GLN B 334 5. .395 37, .296 -47 .981 1, .00 43, .ιg O

ATOM 3140 N ARG B 335 5. .196 39, .524 -48 .676 1, .00 45, .18 N

ATOM 3141 CA ARG B 335 6. .299 39. .982 -47 .847 1, .00 45, .38 C

ATOM 3142 CB ARG B 335 6. .862 41. .310 -48. .347 1, .00 46. .60 C

ATOM 3143 CG ARG B 335 7. .903 41. .304 -49 .525 1. .00 47. .47 C

ATOM 3144 CD ARG B 335 7. .g27 42, .689 -50 .325 1, .00 41. .15 C

ATOM 3145 NE ARG B 335 8. .237 43. .786 -49 .335 1, .00 48. .97 N

ATOM 3146 CZ ARG B 335 9, .468 44. .033 -48. .830 1. ,00 46. .96 C

ATOM 3147 NH1 ARG B 335 10. .521 43. .336 -49. .282 1. .00 51. ,10 N

ATOM 3148 NH2 ARG B 335 9, .663 44. ,968 -47. .899 1, .00 45. ,11 N

ATOM 3149 C ARG B 335 5. ,826 40. .055 -46, ,399 1. ,00 45. 03 C

ATOM 3150 O ARG B 335 S. .616 39. ,88g -45, .480 1. ,00 45. ,37 O

ATOM 3151 N CYS B 336 4, .536 40. ,259 -46, .189 1. .00 44. ,95 N

ATOM 3152 CA CYS B 336 3. .982 40. ,085 -44, .845 1. .00 47. ,27 C

ATOM 3153 CB CYS B 336 2. ,493 40. ,583 -44, .836 1. .00 50. ,01 C

ATOM 3154 SG CYS B 336 2. ,252 42. ,447 -44, .860 1. .00 53. .74 S

ATOM 3155 C CYS B 336 4, ,014 38. ,585 -44, .375 1, ,00 46. ,60 C

ATOM 3156 O CYS B 336 4. ,128 38. 288 -43. ,166 1. ,00 47. 04 O

ATOM 3157 N ILE B 337 3. ,877 37. 635 -45. ,313 1. ,00 44. ,09 N

ATOM 3158 CA ILE B 337 3. ,859 36. ,257 -44, ,877 1. ,00 42. ,89 C

ATOM 3159 CB ILE B 337 3, ,172 35. .418 -46, ,001 1. ,00 43. .12 C

ATOM 3160 CGI ILE B 337 1. ,648 35. 703 -46. ,010 1. ,00 44. 94 C

ATOM 3161 CDl ILE B 337 1. ,09g 35. 467 -47. ,504 1. ,00 50. ,25 C

ATOM 3162 CG2 ILE B 337 3. ,462 34. .006 -45, .886 1. ,00 39. ,94 C

ATOM 3163 C ILE B 337 5. ,292 35. 862 -44. ,593 1. ,00 41. ,18 C

ATOM 3164 O ILE B 337 5. ,591 35. 258 -43. ,580 1. 00 39. 79 O

ATOM 3165 N ASP B 338 6. ,188 36. 233 -45, .501 1. ,00 40. 24 N

ATOM 3166 CA ASP B 338 7, ,581 35. 933 -45, .288 1. ,00 41. ,46 C

ATOM 3167 CB ASP B 338 8. 372 36. 182 -46. .569 1. 00 40. 81 C

ATOM 3168 CG ASP B 338 8. ,085 35. 114 -47. ,625 1. ,00 40. 89 C

ATOM 3169 OD1 ASP B 338 8. ,193 33. 929 -47. ,263 1. 00 43. ,37 O

ATOM 3170 OD2 ASP B 338 7. 784 35. 339 -48. 821 1. 00 44. 92 O

ATOM 3171 C ASP B 338 8. 207 36. 639 -44. ,072 1. 00 41. 98 C

ATOM 3172 O ASP B 338 g. ,168 36. 145 -43. ,509 1. 00 42. 31 O

ATOM 3173 N SER B 339 7. ,618 37. 742 -43. ,602 1. ,00 42. 37 N

ATOM 3174 CA SER B 339 8. 240 38. 398 -42. 432 1. 00 45. og C

ATOM 3175 CB SER B 33 8. 286 39. 917 -42. ,582 1. 00 41. 53 C

ATOM 3176 OG SER B 339 6. ,941 40. 420 -42. ,702 1. ,00 3g. 96 O

ATOM 3177 C SER B 33g 7. ,552 38. 048 -41. ,144 1. 00 47. 78 C

ATOM 3178 O SER B 33g 8. 033 38. 441 -40. 054 1. 00 48. 12 O

ATOM 3179 N GLY B 340 6. 457 37. 271 -41. ,250 1. 00 50. 66 N

ATOM 3180 CA GLY B 340 5. ,701 36. 871 -40. ,082 1. 00 53. 80 C

ATOM 3181 C GLY B 340 4, 718 37. 946 -39. 605 1. 00 56. 68 C

ATOM 3182 O GLY B 340 4. 093 37. 747 -38. 573 1. 00 57. 67 O

ATOM 3183 N LEU B 341 4. ,569 39. 053 -40. 343 1. 00 58. 12 N ATOM 3184 CA LEU B 341 3.492 40.056 -40.093 00 60.97 C

ATOM 3185 CB LEU B 341 3.624 41.311 -41.012 00 58.85 C

ATOM 3186 CG LEU B 341 4.767 42.283 -40.553 00 63.26 C

ATOM 3187 CDl LEU B 341 5.162 43.455 -41.536 00 58.55 C

ATOM 3188 CD2 LEU B 341 4.633 42.788 -39.013 00 58.55 C

ATOM 3189 C LEU B 341 2.079 39.464 -40.199 00 62.99 C

ATOM 3190 O LEU B 341 1.155 39.903 -39.534 00 63.32 O

ATOM 3191 N TRP B 342 1.912 38.484 -41.071 00 65.78 N

ATOM 3192 CA TRP B 342 0.651 37.802 -41.209 1.00 68.54 C

ATOM 3193 CB TRP B 342 0.123 38.347 -42.411 ,00 69.39 C

ATOM 3194 CG TRP B 342 -1.616 38.003 -42.345 00 77.77 C

ATOM 3195 CDl TRP B 342 -2.533 38.435 -41.406 00 82.45 C

ATOM 3196 NE1 TRP B 342 -3.779 37.918 -41.679 00 87.04 N

ATOM 3197 CE2 TRP B 342 -3.695 37.138 -42.806 00 88.02 C

ATOM 3198 CD2 TRP B 342 -2.340 37.164 -43.247 00 83.78 C

ATOM 319g CE3 TRP B 342 -1.989 36.435 -44.388 00 85.76 C

ATOM 3200 CZ3 TRP B 342 -2.978 35.690 -45.050 00 91.89 C

ATOM 3201 CH2 TRP B 342 .319 35.675 -44.588 00 94.37 C

ATOM 3202 CZ2 TRP B 342 .694 36.3gi -43.465 1.00 92.61 C

ATOM 3203 C TRP B 342 .850 36.258 -41.264 1.00 67.98 C

ATOM 3204 O TRP B 342 .617 35.727 -42.086 1.00 66.04 O

ATOM 3205 N VAL B 343 .189 35.558 -40.339 1.00 68.73 N

ATOM 3206 CA VAL B 343 0.167 34.103 -40.391 69.63 C

ATOM 3207 CB VAL B 343 0.279 33.413 -38.991 69.83 C

ATOM 3208 CGI VAL B 343 0.582 31.876 -39.195 68.69 c

ATOM 320g CG2 VAL B 343 1.310 34.074 -38.102 67.03 c

ATOM 3210 C VAL B 343 -1.105 33.635 -41.135 70.73 c

ATOM 3211 O VAL B 343 -2.209 33.873 -40.666 69.58 0

ATOM 3212 N PRO B 344 -0.956 32.g74 -42.287 1.00 73.28 N

ATOM 3213 CA PRO B 344 -2.134 32.397 -42.962 1.00 76.01 C

ATOM 3214 CB PRO B 344 -1.551 31.852 -44.268 1.00 75.25 C

ATOM 3215 CG PRO B 344 -0.352 32.660 -44.428 1.00 73.23 C

ATOM 3216 CD PRO B 344 0 ..277 32.657 -43.039 1.00 72.21 C

ATOM 3217 C PRO B 344 -2 ..702 31.303 -42.042 1.00 77.97 C

ATOM 3218 O PRO B 344 -1. .984 30.414 -41.651 1.00 76.21 0

ATOM 3219 N ASN B 345 -3. .961 31.467 -41.626 1.00 82.59 N

ATOM 3220 CA ASN B 345 -4 ..55g 30.615 -40.589 1.00 85.96 C

ATOM 3221 CB ASN B 345 -5.873 31.221 -40.042 1.00 86.69 C

ATOM 3222 CG ASN B 345 -6.007 31.080 -38.501 1.00 87.74 C

ATOM 3223 OD1 ASN B 345 -5.033 30.779 -37.786 1.00 87.28 O

ATOM 3224 ND2 ASN B 345 -7.225 31.298 -37.9g9 1.00 87.60 N

ATOM 3225 C ASN B 345 -4.776 2g.244 -41.209 1.00 87.48 C

ATOM 3226 O ASN B 345 -4.832 28.230 -40.523 1.00 87.53 O

ATOM 3227 N SER B 346 -4.861 29.269 -42.534 1.00 89.50 N

ATOM 3228 CA SER B 346 -4.975 28.102 -43.392 ,00 91.62 C

ATOM 3229 CB SER B 346 -6.476 27.737 -43.626 ,00 91.75 C

ATOM 3230 OG SER B 346 -7.251 27.705 -42.411 .00 90.90 O

ATOM 3231 C SER B 346 -4.220 28.470 -44.714 ,00 92.92 C

ATOM 3232 O SER B 346 -4.790 29.114 -45.626 ,00 93.67 O

ATOM 3233 N ALA B 347 -2.946 28.054 -44.787 ,00 93.65 N

ATOM 3234 CA ALA B 347 -1.925 28.438 -45.818 ,00 94.43 c

ATOM 3235 CB ALA B 347 -0.851 27.34g -45.881 ,00 94.83 c

ATOM 3236 C ALA B 347 -2.225 28.962 -47.271 ,00 94.55 c

ATOM 3237 O ALA B 347 -1.870 30.087 -47.714 00 g4.50 0

ATOM 3238 OXT ALA B 347 -2.771 28.262 -48.139 ,00 94.41 0

ATOM 3239 O HOH W 1 41.552 59.g96 -8.033 ,00 35.64 0

ATOM 3240 O HOH W 2 53.613 55.826 -16.818 ,00 32.83 0

ATOM 3241 O HOH W 3 55.156 63.522 3.344 .00 34.88 0

ATOM 3242 O HOH W 4 51.957 58.092 -2.178 ,00 32.39 0

ATOM 3243 O HOH W 5 47.947 71.606 8.617 ,00 34.94 0

ATOM 3244 O HOH W 6 37.300 64.149 0.472 .50 23.07 0

ATOM 3245 O HOH W 7 55.180 42.801 -16.779 00 37.60 0

ATOM 3246 O HOH W 8 54.073 60.963 2.951 .00 53.61 0

ATOM 3247 O HOH W g 52.558 63.626 -17.543 ,00 40.51 0

ATOM 3248 O HOH W 10 56.712 59.985 294 00 27.43 0

ATOM 3249 O HOH W 11 51.783 40.328 933 00 55.71 0

ATOM 3250 O HOH W 12 6.608 31.414 -45.539 ,00 52.53 0

ATOM 3251 O HOH W 13 53.482 75.802 9.523 00 46.56 0

ATOM 3252 0 HOH W 14 42.595 61.343 13.914 00 33.43 o

ATOM 3253 0 HOH W 15 63.719 56.738 -1.538 00 31.76 0

ATOM 3254 0 HOH W 16 60.027 61.073 -12.195 ,00 45.05 0

ATOM 3255 0 HOH W 17 49.018 59.102 839 00 40.62 0

ATOM 3256 0 HOH W 18 55.088 67.564 531 00 38.02 0

ATOM 3257 0 HOH W 19 57.351 61.915 224 00 32.64 0

ATOM 3258 0 HOH W 20 50.449 61.408 190 00 45.61 0

ATOM 325g 0 HOH W 21 57.184 59.707 052 00 33.44 0

ATOM 3260 0 HOH w 22 56.057 56.602 -2.943 1.00 28.59 0 ATOM 3261 O HOH W 23 53.241 74.667 405 1.00 34.35 0

ATOM 3262 O HOH W 24 51.517 42.521 073 1.00 29 .22 0

ATOM 3263 O HOH W 25 45.373 59.255 -7.819 1.00 48 .84 0

ATOM 3264 O HOH W 26 53.906 57.217 -4.433 32 .32 0

ATOM 3265 O HOH w 27 39.937 52.302 -14.927 37 .41 0

ATOM 3266 O HOH w 28 59.378 42.001 -6.340 43 .12 0

ATOM 3267 O HOH w 29 46.821 40.808 -0.957 34 .49 0

ATOM 3268 O HOH w 30 56.203 44.202 -14.512 49 .09 0

ATOM 3269 O HOH w 31 41.848 72.97g 6.114 37 .79 0

ATOM 3270 O HOH w 32 41.549 53.280 7.913 41 .89 0

ATOM 3271 O HOH w 33 62.010 48.320 -12.734 40 .91 0

ATOM 3272 O HOH w 34 51.315 3g.980 -11.272 74 .47 0

ATOM 3273 O HOH w 35 58.908 57.106 -17.317 33 .65 0

ATOM 3274 O HOH w 36 30.369 56.583 3.270 36 .76 0

ATOM 3275 O HOH w 37 57.667 51.697 -7.164 37 .76 0

ATOM 3276 O HOH w 38 50.058 62.747 -29.407 41 .36 0

ATOM 3277 O HOH w 39 39.207 65.304 20.763 61 .42 0

ATOM 3278 O HOH w 40 54.662 63.507 19.517 56 .42 0

ATOM 3279 O HOH w 41 62.599 43.261 2.737 1.00 41 .go 0

ATOM 3280 O HOH w 42 62.964 5g.485 -11.260 46 .01 0

ATOM 3281 O HOH w 43 36.294 59.859 0.053 30 .46 0

ATOM 3282 O HOH w 44 46.470 61.602 -2.905 43 .04 0

ATOM 3283 O HOH w 45 69.702 53.693 -3.698 60 .91 o

ATOM 3284 O HOH w 46 52.175 58.534 -10.409 43 .20 o

ATOM 3285 O HOH w 47 61.300 61.0g6 13.104 45 .04 0

ATOM 3286 0 HOH w 48 60.904 41.774 11.691 55 .21 0

ATOM 3287 0 HOH w 49 51.424 61.059 -5.103 54 .65 0

ATOM 3288 0 HOH w 50 55.672 62.932 -16.326 45 .37 0

ATOM 3289 0 HOH w 51 48.555 61.128 17.886 52 .22 0

ATOM 3290 0 HOH w 52 57.889 85.395 1.352 65, .84 0

ATOM 3291 0 HOH w 53 59.145 53.584 -6.445 52 .49 0

ATOM 3292 0 HOH w 54 40.644 55.912 -35.000 1.00 50, .79 o

ATOM 3293 0 HOH w 55 61.771 64.475 -4.614 1.00 42, .29 0

ATOM 3294 0 HOH w 56 64.788 50.gi4 -10.774 1.00 57, .47 o

ATOM 3295 0 HOH w 57 44.605 43.097 -8.503 1.00 54, .90 0

ATOM 3296 0 HOH w 58 14.542 33.371 -40.888 1.00 55 .26 o

ATOM 3297 0 HOH w 59 46.605 43.143 -20.165 1.00 46, .97 0

ATOM 3298 0 HOH w 60 55.118 58.567 539 57, ,36 o

ATOM 3299 0 HOH w 61 40.605 47.666 630 39, .50 o

ATOM 3300 0 HOH w 62 58.g65 62.185 14.428 44. ,08 0

ATOM 3301 0 HOH w 63 59.357 40.940 14.561 42, .66 0

ATOM 3302 0 HOH w 64 63.636 50.247 -13.055 45. ,91 0

ATOM 3303 0 HOH w 65 41.196 65.082 22.501 62, .65 0

ATOM 3304 0 HOH w 66 54.669 63.834 -0.783 48. .81 0

ATOM 3305 0 HOH w 67 54.199 62.328 -3.404 57. .43 o

ATOM 3306 0 HOH w 68 50.082 72.610 2.704 39. .98 0

ATOM 3307 0 HOH w 69 32.965 55.524 -0.657 55. .92 0

ATOM 3308 0 HOH w 70 59.058 66.809 -6.735 44. ,87 0

ATOM 3309 0 HOH w 71 61.729 53.486 -7.304 50. ,22 o

ATOM 3310 0 HOH w 72 57.150 37.396 -2.386 57. ,11 o

ATOM 3311 0 HOH w 73 38.748 71.210 12.842 50. ,95 o

ATOM 3312 0 HOH w 74 46.466 71.816 21.880 66. 22 0

ATOM 3313 0 HOH w 75 56.461 45.670 -34.294 67. ,30 0

ATOM 3314 0 HOH w 76 50.775 42.445 14.188 51. 59 0

ATOM 3315 0 HOH w 77 60.430 53.925 22.765 58. ,43 0

ATOM 3316 0 HOH w 78 52.480 61.883 1.394 1.00 49. 59 0

ATOM 3317 0 HOH w 7 35.764 58.520 -32.320 1.00 67. 22 o

ATOM 3318 0 HOH w 80 66.460 47.427 -13.734 1.00 59. 46 0

ATOM 3319 0 HOH w 81 56.323 66.823 -5.958 1.00 75. 74 0

ATOM 3320 0 HOH w 82 17.604 33.351 -38.588 1.00 70. 00 0

ATOM 3321 0 HOH w 83 34.025 51.681 6.776 1.00 54. 99 o

ATOM 3322 0 HOH w 84 41.865 57.238 -33.445 1.00 50. 83 0

ATOM 3323 0 HOH w 85 3.810 34.100 -41.665 1.00 46. 36 0

ATOM 3324 0 HOH w 86 65.057 50.478 -5.110 1.00 46. 28 0

ATOM 3325 0 HOH w 87 38.558 51.893 g.485 1.00 43. 85 0

ATOM 3326 0 HOH w 88 44.027 73.344 2.161 43. 96 0

ATOM 3327 0 HOH w 89 1.5g2 50.983 -42.473 75. 22 o

ATOM 3328 0 HOH w 90 44.710 42.924 -18.245 53. 40 0

ATOM 3329 0 HOH w 91 50.688 49.884 -33.385 64. 21 o

ATOM 3330 0 HOH w g2 72.0g7 56.322 -24.644 76. 16 0

ATOM 3331 0 HOH w 93 62.477 64.532 16.167 51. 95 0

ATOM 3332 0 HOH w 94 36.603 56.501 -33.626 45. 39 0

ATOM 3333 0 HOH w 95 52.34g 78.2g5 12.130 59. 14 0

ATOM 3334 0 HOH w 96 44.3gθ 63.777 ig.956 1.00 49. 71 0

ATOM 3335 0 HOH w 97 72.529 48.240 2.101 1.00 50. 62 0

ATOM 3336 0 HOH w 98 49.338 5g.433 -18.622 1.00 46. 18 0

ATOM 3337 0 HOH w 99 56.635 4g.l55 26.717 1.00 66. 35 0 ATOM 3338 O HOH W 100 39.138 67.312 16.115 1.00 47.20 O

ATOM 3339 O HOH W 101 24 .657 33 .407 -38 .463 1 .00 ε .39 0

ATOM 3340 O HOH W 102 45 .395 63 .854 -32 .171 1 .00 60 .09 0

ATOM 3341 O HOH W 103 64 .926 52 .971 1 .832 1 .00 48 .98 0

ATOM 3342 O HOH W 104 61 .113 61 .812 -5 .386 1 .00 61 .42 0

ATOM 3343 O HOH W 105 70 .432 48 .040 15 .48g 1 .00 49 .15 0

ATOM 3344 O HOH W 106 57 .371 77 .243 13 .g88 1 .00 54 .90 0

ATOM 3345 O HOH W 107 56 .064 39 .431 -39 .009 1 .00 95 .66 0

ATOM 3346 O HOH W 108 sg .018 38 .519 -21 .590 1 .00 52 .58 0

ATOM 3347 O HOH W 109 72 .063 60 .266 10 .824 1 .00 59 .86 0

ATOM 3348 O HOH W 110 35 .850 47 .927 -1 .729 1 .00 72 .14 0

ATOM 3349 O HOH W 111 36 .092 70 .592 8 .069 1 .00 48 .92 0

ATOM 3350 O HOH W 112 10 .977 40 .664 -51 .342 1 .00 54 .15 0

ATOM 3351 O HOH W 113 52 .664 72 .765 14 .838 1 .00 47 .39 0

ATOM 3352 O HOH W 114 41 .598 46 .653 9 .144 1 .00 57 .37 0

ATOM 3353 O HOH W 115 55 .112 45 .37g -32 .087 1 .00 67 .58 0

ATOM 3354 O HOH W 116 10 .166 44 .675 -38 .535 1 .00 65 .35 o

ATOM 3355 O HOH W 117 48 .655 56 .344 -11 .gβo 1 .00 47 .94 0

ATOM 3356 O HOH W 118 44 .510 66 .037 19 .984 1 .00 52 .15 0

ATOM 3357 O HOH W 119 33 .723 50 .050 -36 .091 1 .00 50 .4g o

ATOM 3358 O HOH W 120 53 .288 41 .84g -17 .617 1 .00 58 .14 0

ATOM 3359 O HOH W 121 s .370 44 .g99 -10 .229 1 .00 52 .54 0

ATOM 3360 O HOH W 122 54 . 26 81 .908 6 .910 1 .00 64 .47 0

ATOM 3361 0 HOH W 123 41 .123 46 .050 -10 .366 1 .00 56 .24 0

ATOM 3362 0 HOH w 124 55 .446 40 .047 -15. .074 1 .00 47 .48 0

ATOM 3363 0 HOH w 125 60 .373 42 .714 6 .371 1 .00 41 .61 0

ATOM 3364 0 HOH w 126 50 .743 57 .39g -12 .091 1 .00 46 .61 0

ATOM 3365 0 HOH w 127 57 .248 58 ,g46 22 .697 1 .00 66 .54 o

ATOM 3366 0 HOH w 128 33 .962 68 .695 8. .926 1 .00 61 .30 o

ATOM 3367 0 HOH w 129 35, .536 52, .761 1. .608 1 .00 42, .g2 0

ATOM 3368 0 HOH w 130 62 .355 65 .og -27 .547 1 .00 66 .7g 0

ATOM 336g 0 HOH w 131 53 .998 65, ,4ig -16. .424 1. .00 56. .68 0

ATOM 3370 0 HOH w 132 41 .847 67 .771 -5 .530 1 .00 52. .62 0

ATOM 3371 0 HOH w 133 49 .669 70, .799 -21. .178 1. .00 46. .65 0

ATOM 3372 0 HOH w 134 63 .441 71 .287 -22 .167 1 .00 65. .go 0

ATOM 3373 0 HOH w 135 45, .94g 56, .656 -14, .437 1. .00 55, .77 0

ATOM 3374 0 HOH w 136 68 .515 55 .800 -14, .067 1. .00 60, .01 0

ATOM 3375 0 HOH w 137 52 .756 48, .431 16, .746 1. .00 43, .92 o

ATOM 3376 0 HOH w 138 31 .324 56, .498 9 .494 1. .00 58, .08 0

ATOM 3377 0 HOH w 139 41 .213 73, .672 10, .639 1, .00 62. .28 0

ATOM 3378 0 HOH w 140 31 .313 48 .872 -37, .065 1. .00 55, .87 0

ATOM 337g 0 HOH w 141 47, .654 69, .091 -21, .500 1, .00 51. .98 o

ATOM 3380 0 HOH w 142 64, .931 45. ,032 -1. .369 1. ,00 66. ,85 o

ATOM 3381 0 HOH w 143 72, .786 49, .565 -21, .856 1, ,00 82. .69 0

ATOM 3382 0 HOH w 144 32, .252 52. .081 -36, .071 1, ,00 57. .26 o

ATOM 3383 0 HOH w 145 47 .926 59. .950 -4, .984 1, .00 64. ,19 o

ATOM 3384 0 HOH w 146 45, .722 42. .520 -29, .637 1. .00 66. .19 o

ATOM 3385 0 HOH w 147 46 .057 66, .958 -7, .593 1, .00 67. .21 0

ATOM 3386 0 HOH w 148 33, .865 53, ,301 -7, .586 1. .00 54. .24 o

ATOM 3387 0 HOH w 149 45 .312 77, .975 18, .174 1, .00 55. .66 0

ATOM 3388 0 HOH w 150 46, .834 72, ,097 16, .569 1. ,00 56. ,34 o

ATOM 338g 0 HOH w 151 47 .198 43, .317 -25, .511 1, .00 62. .22 0

ATOM 3390 0 HOH w 152 53, .046 44. ,155 -31, .758 1. ,00 64. .05 o

ATOM 3391 0 HOH w 153 37 ,4gg 66, .317 22, .493 1, ,00 76. .13 0

ATOM 3392 0 HOH w 154 60, .012 64, .015 15, .783 1. .00 62. .99 o

ATOM 3393 0 HOH w 155 8 .233 37, .838 -37 .652 1. .00 61. ,60 0

ATOM 3394 0 HOH w 156 62, .498 45, .884 -5, ,420 1. .00 59. ,96 o

ATOM 33g5 0 HOH w 157 47 .866 68, ,865 -2 .068 1, .00 48. ,11 0

ATOM 3396 0 HOH w 158 59, .106 69, ,656 11, .047 1. ,00 70. ,21 o

ATOM 3397 0 HOH w 159 42 .518 74, .257 4, .002 1, .00 47. , 5 0

ATOM 3398 0 HOH w 160 54, .856 58, .402 -9, .282 1. ,00 54. ,98 o

ATOM 3399 0 HOH w 161 54. .443 73. .835 -4. .024 1. ,00 57. ,73 0

ATOM 3400 0 HOH w 162 65, .457 79. .383 12. .462 1. ,00 56. ,13 0

ATOM 3401 0 HOH w 163 60. .487 66, .857 -15. .836 1. ,00 74. 65 0

ATOM 3402 0 HOH w 164 53. .199 66, .188 2, .769 1, ,00 46. ,26 0

ATOM 3403 0 HOH w 165 49, .004 41, ,625 -ιg. ,456 1. .00 58. ,30 0

ATOM 3404 0 HOH w 166 68 .464 62, .537 14. .530 1. ,00 69. ,74 0

ATOM 3405 0 HOH w 167 56, .371 62, .234 -13. ,945 1. ,00 66. 59 0

ATOM 3406 0 HOH w 168 32 .270 61, ,85g 12, .148 1. ,00 53. ,77 0

ATOM 3407 0 HOH w 169 63, .547 50, ,597 -34, .020 1. ,00 56. 31 0

ATOM 3408 owo HOH w 170 49 .151 43, .879 -27, .380 1. .00 81. ,98 0

ATOM 3409 owo HOH w 171 52, .067 66, .467 0, ,366 1. ,00 64. 89 0

ATOM 3410 owo HOH w 172 -5. .361 34 ,305 -40, ,g46 1, ,00 88. ,41 0

ATOM 3411 owo HOH w 173 43 .793 68, .335 -2, .106 1. .00 52. ,64 0

ATOM 3412 owo HOH w 174 65 .055 55 ,902 -33, .770 1. .00 48. ,79 o

ATOM 3413 owo HOH w 175 36 .889 51, .870 -IS, .584 1. ,00 57. ,54 0

ATOM 3414 owo HOH w 176 -6 .279 44 .807 -52 .713 1, .00 72. ,23 0 ATOM 3415 OWO HOH W 177 5g .802 48.58g -9.580 1.00 58.26 O

ATOM 3416 OWO HOH W 178 47.171 78.722 10.709 1.00 55.61 O

ATOM 3417 OWO HOH W 179 38.181 66.131 0.000 0.50 59.03 O

ATOM 3418 OWO HOH W 180 67.735 56.869 -4.584 1.00 82.15 O

Claims

CLAIMS i

1. A crystal of a complex between Hsp90 and p50^cdc37 having a space group P3ι21 or its enantiomorph and unit cell dimensions of a = 83.76±0.5 A, c = 148.45±0.5 A.

2. A crystal according to claim 1, having unit cell dimensions of a = 83.76+0.2 A, c = 148.45+0.2 A.

3. A crystal according to claim 1 or claim 2, having unit cell dimensions of a = 83.76 A, c = 148.45 A.

4. A crystal according to any of claims 1 to 3 wherein the Hsp90 lacks some or all of the middle (M) and C-terminal domains.

5. A crystal according to claim 4 wherein the Hsp90 corresponds to residues 1 to 208 of yeast Hsp90.

6. A crystal according to any one of the preceding claims wherein the p50^cdc37 lacks some or all of the N-terminal domain.

7. A crystal according to claim 6 wherein the p50^cdc37 corresponds to residues 138 to 378 of human p50^cdc37.

8. A crystal according to any one of the preceding claims wherein the Hsp90 is human or yeast.

9. A crystal according to any one of the preceding claims wherein the p50^cdc37 is human or yeast.

10. A crystal of a complex between Hsp90 and p50^cdc37 having the three dimensional atomic coordinates of Table 2.

11. A method of determining the structure of a complex between Hsp90 and p50^cdc37 comprising the step of X-ray diffraction analysis of a crystal according to any one of the preceding claims .

12. A method of analysing binding between a complex of Hsp90 and p50^cdc37 and a ligand binding to either or both of Hsp90 and p50^cdc37, the method comprising the step of employing (i) X-ray crystallographic diffraction data from the complex between Hsp90, p50^cdc37 and said ligand, and (ii) a three-dimensional structure of a complex between Hsp90 and p50^cdc37 defined by atomic coordinate data according to Table 2, to generate a difference Fourier electron density map of the complex between Hsp90, p50^cdc37 and said ligand.

13. A method of determining a three dimensional structure for a complex between Hsp90 and p50^cdc37 comprising the steps of: (a) aligning a representation of an amino acid sequence of a target Hsp90 and/or p50^cdc37 with the amino acid sequence of yeast Hsp70 and/or human p50^cdc37 to match homologous regions of the amino acid sequences; (b) modelling the structure of the matched homologous regions of the target Hsp90 and/or p50^cdc3? on the structure of the corresponding regions of yeast Hsp90 and/or human p50^cdc37 as defined by Table 2 ; and (c) determining a conformation for the target Hsp90 and/or p50^cdc37 which substantially preserves the structure of said matched homologous regions .

14. A method of determining a three dimensional structure for a complex between Hsp90 and p50^cdc37, comprising the steps of; providing the co-ordinates of Table 2, and positioning the coordinates in the crystal unit cell of a target Hsp90 and/or p50^cdc37 so as to provide a structure for said target Hsp90 and/or p50^cdc37.

15. A method according to claim 13 or claim 14 wherein said target Hsp90 is human Hsp90.

16. A computer system or computer-readable media containing either (a) atomic coordinate data of Table 2, said data defining the three-dimensional structure of a complex between Hsp90 and p50^cdc37, or at least selected coordinates thereof; (b) structure factor data for a complex between Hsp90 and p50-^d-³⁷, _saic[ structure factor data being derivable from the atomic coordinate data of Table 2; (c) a Fourier transform of atomic coordinate data according to Table 2, or at least selected coordinates thereof; (d) atomic coordinate data of a target complex between Hsp90 and p50^cdc37 generated by homology modelling of the target based on the data of Table 2; (e) atomic coordinate data of a target complex between Hsp90 and p_5Q ^cdc37 g_enerated by interpreting X-ray crystallographic data or NMR data by reference to the data of Table 2; or (f) structure factor data derivable from the atomic coordinate data of (c) , (d) or (e) .

17. A method for modelling an interaction between a complex of Hsp90 and p50^cdc37 PKB and a candidate compound, comprising the steps of:

(a) employing three-dimensional atomic coordinate data of Table 2 to characterise at least one binding site;

(b) providing the structure of said candidate compound

(c) fitting said candidate compound to the binding site.

18. A method for identifying an agent compound which modulates Hsp90 activity, comprising the steps of:

(a) employing a three-dimensional structure of a complex between Hsp90 and p50^cdc37, defined by atomic coordinate data according to Table 2, to characterise at least one binding site;

(b) providing the structure of a candidate agent compound;

(c) fitting the candidate agent compound to the binding site; and (d) selecting the candidate agent compound.

19. A method according to claim 18, wherein said binding site comprises all or part of the ATP binding site of Hsp90.

20. A method according to claim 19, wherein said binding site comprises one or more amino acid residues corresponding to Glu

33 or Asp 79 of yeast Hsp90.

21. A method according to claim 19 or claim 20, wherein said binding site comprises amino acid residues corresponding to Arg 167 of human p50^cdc37.

22. A method according to claim 18, wherein, when the candidate agent compound is fitted to the binding site, an interaction between said candidate agent compound and the binding site mimics an interaction formed between one or more of the following sets of residues on binding of human p50^cdc37 and yeast Hsp90:

Ala 103 of Hsp90 and Met 164 of p50^cdc37; Glu 106 of Hsp90 and Ala 204 of p50^cdc37; Ala 107 of Hsp90 and Met 164 of p50^cdc37; Ser 109 of Hsp90 and Lys 202 of p50^cdc37; Ala 110 of Hsp90 and Ala 204 of p50^cdc37; Ala 112 of Hsp90 and Met 164 of p50^cdc37; Met 116 of Hsp90 and Met 164 of p50^cdc37 _; Gin 119 of Hsp90 and Leu 165 of p50^cdc37; Gin 119 of Hsp90 and Glu 221 of p50^cdc37; Phe 120 of Hsp90 and Met 164 of p50^cdc37; Glu 33 of Hsp90 and Arg 167 of _p50cdc37. _{Ser 36 Qf Hsp90 and Arg} 1S7 of p50^cdc37..

23. A method according to claim 18 comprising comparing the three-dimensional structure of the complex between Hsp90 and p50^cdc37 with a three dimensional structure of Hsp90 not in such a complex to identify a binding site which is:

(i) exposed on Hsp90 when not in said complex but is not exposed in said complex; or

(ii) exposed only in said complex; or (iii) exposed on Hsp90 both when in said complex and when not in said complex.

24. A method according to claim 23 (i) wherein said binding site is masked sterically or by a conformational change on binding of p50^cdc37 to Hsp90.

25. A method according to claim 23 (ii) wherein said binding site comprises residues from both p50^cdc37 and Hsp90, or is exposed by a conformational change on binding of p50^cdc37 to Hsp90.

26. A method according to any one of claims 18 to 25 wherein: a plurality of binding sites are characterised and a plurality of agent compounds are fitted to said sites; and said agent compounds are linked to form a potential modulator compound .

27. A method according to any one of claims 18 to 26 comprising selecting said candidate agent compound by computationally screening a database of compounds for interaction with said binding site.

28. A method according to any one of claims 18 to 27 which comprises the further steps of:

(e) obtaining or synthesising the candidate agent compound; and (f) contacting the candidate agent compound with Hsp90 and/or a complex between p50^cdc37 and Hsp90. to determine the ability of the candidate agent compound to modulate the activity of Hsp90.

29. A method according to claim 28 wherein ability of the candidate agent compound to modulate the activity of Hsp90 is determined by measuring ATPase activity of Hsp90 or the ability of Hsp90 to modulate the activity of a client protein.

30. A method according to claim 29 wherein the client protein is a kinase.

Ill

31. A method according to any one of claims 18 to 27 which comprises the further steps o : (e) obtaining or synthesising the candidate agent compound; (f) forming a complex between Hsp90 and the candidate agent compound and optionally p50^cdc37; and (g) analysing said complex by X-ray crystallography or NMR spectroscopy to determine the ability of the candidate agent compound to interact with Hsp90.

32. A method for determining the ability of a candidate agent compound to modulate Hsp90 activity, comprising contacting an Hsp90 protein with p50^cdc37 and the candidate agent compound, wherein said Hsp90 lacks all or substantially all of the C- terminal domain.

33. A method according to claim 32 wherein the Hsp90 protein lacks all or substantially all of the middle (M) domain.

34. A method according to claim 33 wherein the Hsp90 protein comprises or consists of the portion corresponding to amino acid residues 1 to 208 of yeast Hsp90.

35. A method according to any one of claims 32 to 34 further comprising contacting an Hsp90 protein with the candidate agent compound in the absence of p50^cdc37.

36. A method according to any one of claims 32 to 35 further comprising contacting a Hsp90 protein having ATPase activity with the candidate agent compound and optionally p50^cdc37, and determining the effect of said candidate compound on said

ATPase activity.

37. A compound which is identified as a modulator of PKB activity by the method of any one of claims 18 to 36.

38. A method for preparing a medicament, pharmaceutical composition or drug, the method comprising: having identified a Hsp90 modulator molecule by a method of any one of claims 18 to 36, formulating the modulator molecule into a pharmaceutical composition by admixture with a pharmaceutically acceptable carrier.

39. A method according to claim 38 wherein the modulator is an inhibitor of Hsp90.

40. A method according to claim 38 or claim 39 further comprising the step of optimising the structure of the modulator molecule for in vivo administration.