AU5660900A - Crystalline zap family proteins - Google Patents

Description

AUSTRALIA

PATENTS ACT 1990 DIVISIONAL APPLICATION NAME OF APPLICANT(S): Ariad Pharmaceuticals, Inc.

ADDRESS FOR SERVICE: DAVIES COLLISON CAVE Patent Attorneys 1 Little Collins Street Melbourne, 3000.

INVENTION TITLE: "Crystalline zap family proteins" The following statement is a full description of this invention, including the best method of performing it known to us: -1A- Crystalline ZAP Family Proteins This application is a divisional of Australian Patent Application No. 69606/96, the entire contents of which are incorporated herein by reference.

Copyright Notice A portion of the disclosure of this patent document contains material which is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or patent disclosure, as it appears in the Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever.

Field of the Invention The invention relates to human ZAP-70, and in particular, to the region of ZAP-70 containing the tandem Src homology-2 domains, to crystalline forms thereof, liganded or 1 5 unliganded, which are particularly useful for the determination of the three-dimensional S structure of the protein. The three dimensional structure of the tandem SH2 region of ZAP S.'provides information useful for the design of pharmaceutical compositions which inhibit the biological function of ZAP and other proteins of the ZAP family, particularly those biological functions mediated by molecular interactions involving one or both SH2 domains.

oo Background o. Safe and effective immunosuppressive agents are required for the treatment of patients .to suffering from autoimmune disorders and for recipients of transplanted organs or tissues. For :2 5 instance, in the absence of an effective immunosuppressive agent, patients often reject a S" transplanted organ, sometimes with fatal consequences. The immunosuppressive agent must block the immune response, but must also be sufficiently well tolerated by the body to permit chronic application. For instance, one compound with immunosuppressive activity, FK506, has been used to prevent rejection of transplanted livers. However, severe kidney toxicity has been 3 0 observed in patients receiving FK506, in some cases requiring kidney transplant following the liver transplant.

Research aimed at discovering new immunosuppressive agents has been hampered by the lack of information about precise molecular mechanisms of the immune response. As a result, random 3 5 screening of compounds has accounted for a substantial share of research efforts aimed at identifying new immunosuppressive drugs. More recently, "structure-based" approaches to drug design have been attempted. For example, compounds designed to bind to the protein FKBP, one of the cellular targets of FK506, were synthesized as candidate immunosuppressive agents.

Those efforts were unfortunately doomed by the lack of understanding of the actual molecular mechanism of immunosuppression mediated by FK506. It is now known that FK506 binds in a complex with two proteins, FKBP and calcineurin. FK506's immunosuppressive effects are due to the inhibition of calcineurin in T cells. However, since calcineurin is present and important in other cells, FK506 affects other cells and tissues leading to undesired effects.

Meanwhile, independent efforts have led to the identification of a protein tyrosine kinase, ZAPas a critical mediator of the immune response. Blocking the biological function of will lead to immunosuppression. Unfortunately, until now, three-dimensional structural details of ZAP-70 have been completely unknown. In the absence of three-dimensional 1 0 structural details for that protein, designing inhibitors based on that structure would have been impossible. We have now obtained crystals of a critical region of ZAP-70 containing its tandem SH2 domains, with and without bound ligands of various types, and have determined its three dimensional structure. With this information, it is now possible for the first time to rationally design inhibitors of ZAP-70 which can function as immunosuppressive agents, e.g. compounds 1 5 which inhibit molecular interactions involving one or both of the ZAP-70 SH2 domains.

Although the three-dimensional structures for several individual SH2 domains of other proteins are known, no one has heretofore reported determining the three-dimensional structure of a tandem SH2 region. And, as we discuss below, the three-dimensional coordinates of previously known SH2 domains would have been insufficient to solve the structure of the 20 ZAP-70 tandem SH2 region.

o Summary of the Invention

S

This invention concerns the region of human ZAP-70 spanning its two SH2 domains. We refer to 2 5 that region as the "ZAP tandem SH2 region" or simply "ZAP-NC", since the region contains both the more N-terminal SH2 domain and the more C-terminal SH2 domain of human (see FIG. The invention begins with obtaining crystals of human ZAP-NC, complexed or uncomplexed with various ligands, of sufficient quality to determine the three dimensional (tertiary) structure of the protein by X-ray diffraction methods.

In considering our work, it should be appreciated that obtaining protein crystals in any case is a somewhat unpredictable art, especially in cases in which the practitioner lacks the guidance of prior successes in preparing and/or crystalizing any closely related proteins. Obtaining our first crystals of ZAP-NC was therefore itself an unexpected result. In addition, our determination of the three-dimensional structure of ZAP-NC represents the first solution of a three-dimensional structure for a tandem SH2 region from any protein and revealed an unpredicted array of surface features which contained truly surprising structural aspects. Our results are useful in a number of applications.

-2 For example, the knowledge obtained concerning ZAP-NC can be used to model the tertiary structure of related proteins. For instance, the structure of renin has been modeled using the tertiary structure of endothiapepsin as a starting point for the derivation. Model building of cercarial elastase and tophozoite cysteine protease were each built from known serine and cysteine proteases that have less than 35% sequence identity. The resultant models were used to design inhibitors in the low micromolar range. (Proc. Natl. Acad. Sci. 1993, 90, 3583).

Furthermore, alternative methods of tertiary structure determination that do not rely on X-ray diffraction techniques and thus do not require crystallization of the protein, such as NMR techniques, are simplified if a model of the structure is available for refinement using the 1 0 additional data gathered by the alternative technique. Thus, knowledge of the tertiary structure of the ZAP tandem SH2 region provides a significant window to the structure of the other ZAP family members, including for example SYK.

S Knowledge of the three-dimensional structure of a tandem SH2 region such as ZAP-NC provides 1 5 a means for investigating the mechanism of action of the protein and tools for identifying inhibitors of its function. For example, SH2 domains are known to be involved in intramolecular and intermolecular interactions, usually protein-protein interactions, which are critical for biological activity of the SH2-bearing protein. Knowledge of the three- :dimensional structure of the tandem SH2 region allows one to design molecules capable of binding thereto, including molecules which are thereby capable of inhibiting the interaction of the tandem SH2 region with its natural ligand(s).

Accordingly, one object of this invention is to provide a composition comprising a protein in crystalline form having a peptide sequence derived or selected from that of a protein of the ZAP 25 family. The protein will comprise at least one, and preferably two SH2 domains, a protein containing the tandem SH2 region of ZAP-70, SYK or other related tandem SH2 containing protein. In the case of ZAP-70, the protein may comprise a peptide sequence spanning at least amino acid residues 3-279. Such a crystalline composition may contain one or more heavy atoms, one or more lead, mercury, gold and/or selenium atoms, for instance. Such a heavy 3 0 atom derivative may be obtained, for example, by expressing a gene encoding the protein under conditions permitting the incorporation of one or more heavy atom labels as in the incorporation of selenomethionine), reacting the protein with a reagent capable of linking a heavy atom to the protein trimethyl lead acetate) or soaking a substance containing a heavy atom into the crystals.

The protein may be in the form of a complex with one or more ligand molecules, "ligand" being used in the broadest sense, referring to any substance capable of observable binding to the protein. The peptide sequence of naturally occuring ligands ("ITAMs", see below) for a number of SH2 domains is known and consensus sequence information on peptide ligands for SH2 3 domains has been discussed in the scientific literature. In the case of ZAP-70, peptide ligands of 15-19 residues derived in sequence from naturally occuring ligands for ZAP-70 or other SH2 domains may be used. Those ligands typically contain one or two phosphorylated tyrosine residues. Alternatively, one or both of such phosphorylated tyrosine moieties may be replaced by phosphotyrosine mimetic reagents, numerous examples of which are known in the art.

Illustrative crystalline compositions of this invention having various physicochemical characteristics are disclosed infra. Preferred crystalline compositions of this invention are capable of diffracting x-rays to a resolution of better than about 3.5 A, and more preferably to 1 0 a resolution of 2.6 A or better, and even more preferably to a resolution of 2.2 A or better, and are useful for determining the three-dimensional structure of the material. (The smaller the number of angstroms, the better the resolution.) S•Crystalline compositions of this invention specifically include those in which the crystals 1 5 comprise ZAP-family proteins characterized by the structural coordinates set forth in any of o.the accompanying Appendices or characterized by coordinates having a root mean square deviation therefrom, with respect to backbone atoms of amino acids listed in the Appendices, of A or less.

20 Structural coordinates of a crystalline composition of this invention may be stored in a lol* machine-readable form on a machine-readable storage medium, e.g. a computer hard drive, diskette, DAT tape, etc., for display as a three-dimensional shape or for other uses involving computer-assisted manipulation of, or computation based on, the structural coordinates or the three-dimensional structures they define. For example, data defining the three dimensional structure of a protein of the ZAP family, or portions or structurally similar homologues of S such proteins, may be stored in a machine-readable storage medium, and may be displayed as a S* graphical three-dimensional representation of the protein structure, typically using a computer capable of reading the data from said storage medium and programmed with instructions for creating the representation from such data. This invention thus encompasses a machine, such as a computer, having a memory which contains data representing the structural coordinates of a crystalline composition of this invention, e.g. the coordinates set forth in our Appendices, together with additional optional data and instructions for manipulating such data.

Such data may be used for a variety of purposes, such as the elucidation of other related structures and drug discovery.

For example, a first set of such machine readable data may be combined with a second set of machine-readable data using a machine programmed with instructions for using the first data set and the second data set to determine at least a portion of the coordinates corresponding to the second set of machine-readable data. For instance, the first set of data may comprise a Fourier -4transform of at least a portion of the coordinates for ZAP or SYK proteins set forth in the Appendices hereto, while the second data set may comprise X-ray diffraction data of a molecule or molecular complex.

More specifically, one of the objects of this invention is to provide three-dimensional structural information on new complexes of ZAP family members with various ligands, as well as structural information on other tandem SH2 regions, previously unsolved individual SH2 domains, new ZAP family members and muteins or other variants of any of the foregoing. To that end, we provide for the use of the structural coordinates of a crystalline composition of this 1 0 invention, or portions thereof, to solve, e.g. by molecular replacement, the three dimensional structure of a crystalline form of such a protein or protein:ligand complex, typically involving a protein containing at least one SH2 domain. Doing so involves obtaining x-ray diffraction data for crystals of the protein or protein:ligand co-complex for which one wishes to determine the three dimensional structure. Then, one determines the three-dimensional structure of that •o 15 protein or complex by analyzing the x-ray diffraction data using molecular replacement techniques with reference to the previous structural coordinates. As described in US Patent No.

5,353,236, for instance, molecular replacement uses a molecule having a known structure as a starting point to model the structure of an unknown crystalline sample. This technique is based on the principle that two molecules which have similar structures, orientations and positions in the unit cell diffract similarly. Molecular replacement involves positioning the known structure in the unit cell in the same location and orientation as the unknown structure. Once positioned, the atoms of the known structure in the unit cell are used to calculate the structure factors that would result from a hypothetical diffraction experiment. This involves rotating the .o.known structure in the six dimensions (three angular and three spatial dimensions) until alignment of the known structure with the experimental data is achieved. This approximate structure can be fine-tuned to yield a more accurate and often higher resolution structure using various refinement techniques. For instance, the resultant model for the structure defined by the experimental data may be subjected to rigid body refinement in which the model is subjected to limited additional rotation in the six dimensions yielding positioning shifts of under about The refined model may then be further refined using other known refinement methods.

For example, one may use molecular replacement to exploit a set of coordinates such as set forth in Appendix I, Appendix II or Appendix III to determine the structure of a crystalline cocomplex of ZAP-NC, or a portion thereof, with a ligand other than the rl peptide. Likewise one may use that same approach to determine the three dimensional structure of a co-complex of SYK-NC, or a portion thereof, with a ligand therefor.

Another object of the invention is to provide a method for determining the three-dimensional structure of a protein containing at least one SH2 domain, or a co-complex of the protein with a 5 ligand therefor, using homology modeling techniques and structural coordinates tor a composition of this invention. Homology modeling involves constructing a model of an unknown structure using structural coordinates of one or more related proteins, protein domains and/or subdomains. Homology modeling may be conducted by fitting common or homologous portions of the protein or peptide whose three dimensional structure is to be solved to the three dimensional structure of homologous structural elements. Homology modeling can include rebuilding part or all of a three dimensional structure with replacement of amino acids (or other components) by those of the related structure to be solved. For example, using the structural coordinates of ZAP-NC complexed with the ?1 peptide, one may determine the three 1 0 dimensional structure of SYK-NC or a portion thereof, using homology modeling. A set of coordinates defining the three dimensional structure of SYK-C complexed with the peptide ThrpTyr-Glu-Thr-Leu which were obtained from evaluation of NMR data are set forth in Appendix IV. Those coordinates may be stored, displayed, manipulated and otherwise used in like fashion as the ZAP-NC coordinates of Appendices I Ill.

1 Thus, crystalline compositions of this invention provide a starting material for use in solving the three-dimensional structure of other members of the ZAP-70 family of proteins, notably SYK, as well as newly discovered proteins containing at least one SH2 domain and linking polypeptide non-SH2 polypeptide) where the linking polypeptide has at least about 20 peptide sequence similarity, or preferably identity, to a portion (preferably at least six amino acids) of the ZAP-NC or SYK-NC inter-SH2 linking domain. Sequence similarity may be determined using any conventional similarity matrix. See e.g. Dayhoff, Schwartz, R.M.; Orcutt, Atlas of Protein Sequence and Structure 1979, 5, Suppl. 3,345; Greer, J.

Mol. Biol. 1981, 153, 1027; and Gonnet, Cohen, Benner, S.A. Science 1992, 256, 1443. Proteins containing at least one SH2 domain together with non-SH2 domain peptide sequence homologous to the interdomain linker of ZAP or SYK, i.e. containing at least o* peptide sequence identity or similarity as described above, are considered ZAP family members for the purpose of this disclosure.

By way of further example, the structure defined by the machine readable data may be computationally evaluated for its ability to associate with various chemical entities. The term "chemical entity", as used herein, refers to chemical compounds, complexes of at least two chemical compounds, and fragments of such compounds or complexes.

3 5 For instance, a first set of machine-readable data defining the 3-D structure of a ZAP-family protein, or a portion or co-complex thereof, is combined with a second set of machine-readable data defining the structure of a chemical entity or moiety of interest using a machine programmed with instructions for evaluating the ability of the chemical entity or moiety to associate with the ZAP-family protein or portion or complex thereof and/or the location and/or 6 orientation of such association. Such methods provide insight into the location, orientation and energetics of association of the ZAP family protein with such chemical entities.

Chemical entities that are capable of associating with the ZAP family member may inhibit its interaction with naturally occurring ligands for the protein and may inhibit biological functions mediated by such interaction. In the case of ZAP-70, such biological functions include activation of T cells during an immune response. Such chemical entities are potential drug candidates.

1 0 The protein structure encoded by the data may be displayed in a graphical format permitting visual inspection of the structure, as well as visual inspection of the structure's association with chemical entities. Alternatively, more quantitative or computational methods may be used.

For example, one method of this invention for evaluating the ability of a chemical entity to oo •associate with any of the molecules or molecular complexes set forth herein comprises the steps S 1 5 of: a) employing computational means to perform a fitting operation between the chemical entity and a binding pocket or other surface feature of the molecule or molecular complex; and b) analyzing the results of said fitting operation to quantify the association between the chemical entity and the binding pocket.

This invention further provides for the use of the structural coordinates of a crystalline •composition of this invention, or portions thereof, to identify reactive amino acids, such as cysteine residues, within the three-dimensional structure, preferably within or adjacent to a •o 1 ligand binding site; to generate and visualize a molecular surface, such as a water-accessible surface or a surface comprising the space-filling van der Waals surface of all atoms; to calculate and visualize the size and shape of surface features of the protein or complex, e.g., ligand binding pockets: to locate potential H-bond donors and acceptors within the three- .i dimensional structure, preferably within or adjacent to a ligand binding site: to calculate regions of hydrophobicity and hydrophilicity within the three-dimensional structure, preferably within or adjacent to a ligand binding site; and to calculate and visualize regions on or adjacent to the protein surface of favorable interaction energies with respect to selected functional groups of interest amino, hydroxyl, carboxyl, methylene, alkyl, alkenyl, aromatic carbon, aromatic rings, heteroaromatic rings, substituted and unsubstituted phosphates, substituted and unsubstituted phosphonates, substituted and unsubstituted fluoro and difluorophosphonates; etc.). One may use the foregoing approaches for characterizing the protein and its interactions with moieties of potential ligands to design or select compounds capable of specific covalent attachment to reactive amino acids cysteine) and to design or select compounds of complementary characteristics size, shape, charge, hydrophobicity/hydrophilicity, ability to participate in hydrogen bonding, etc.) to surface features of the protein, a set of which may be preselected. Using the structural coordinates, one -7may also predict or calculate the orientation, binding constant or relative affinity of a given ligand to the protein in the complexed state, and use that information to design or select compounds of improved affinity.

In such cases, the structural coordinates of the ZAP family protein, or portion or complex thereof, are entered in machine readable form into a machine programmed with instructions for carrying out the desired operation and containing any necessary additional data, e.g. data defining structural and/or functional characteristics of a potential ligand or moiety thereof, defining molecular characteristics of the various amino acids, etc.

One method of this invention provides for selecting from a database of chemical structures a compound capable of binding to a ZAP family protein. The method starts with structural coordinates of a crystalline composition of the invention, coordinates defining the three dimensional structure of a ZAP family protein or a portion thereof. Points associated with that 1 5 three dimensional structure are characterized with respect to the favorability of interactions with one or more functional groups. A database of chemical structures is then searched for candidate compounds containing one or more functional groups disposed for favorable interaction with the protein based on the prior characterization. Compounds having structures which best fit the points of favorable interaction with the three dimensional structure are thus 20 identified.

It is often preferred, although not required, that such searching be conducted with the aid of a computer. In that case a first set of machine-readable data defining the 3D structure of a ZAPfamily protein, or a portion or protein-ligand complex thereof, is combined with a second set of 2 5 machine readable data defining one or more moieties or functional groups of interest, using a machine programmed with instructions for identifying preferred locations for favorable interaction between the functional group(s) and atoms of the protein. A third set of data, i.e.

data defining the location(s) of favorable interaction between protein and functional group(s) is so generated. That third set of data is then combined with a fourth set of data defining the 3D 3 0 structures of one or more chemical entities using a machine programmed with instructions for identifying chemical entities containing functional groups so disposed as to best fit the locations of their respective favorable interaction with the protein.

Compounds of the structures selected or designed by any of the foregoing means may be tested 3 5 for their ability to bind to a ZAP family protein, inhibit the binding of a ZAP family protein to a natural or non-natural ligand therefor, and/or inhibit a biological function mediated by a ZAP family member.

-8 This invention also provides peptidomimetic methods for designing a compound capable of binding to a ZAP family protein. One such method involves graphically displaying a threedimensional representation based on coordinates defining the three-dimensional structure of a ZAP family protein or a portion thereof complexed with a ligand. Interactions between portions of a ligand and the protein are characterized in order to identify candidate moieties for replacement. One or more portions of the ligand which interact with the protein may be replaced with substitute moieties selected from a knowledge base of one or more candidate substitute moieties, and/or moieties may be added to the ligand to permit additional interactions with the protein.

The computational approaches and structural insights disclosed herein also permit the design or identification of molecules with reduced capability, or substantial inability, to bind to a ZAP family protein. To such end, one may apply the same modeling and computational methods to the o• data described herein, but with the opposite goal, to design or identify compounds which 1 5 lack substantial binding affinity to one or more ZAP family members. That can be useful in research efforts aimed at discovery of inhibitors of SH2-mediated interactions other than those mediated by a ZAP family member. The goal of such efforts are inhibitors of those other SH2mediated interactions which lack ZAP-family mediated activities, such as immunosuppression, which in that context, would be undesired side effects.

0• Compounds first identified by any of the methods described herein are also encompassed by this invention.

Brief Description of the Drawings FIG. 1A Backbone ribbon representation of the overall fold of the complex of ZAP-NC and the 'oo* ilpeptide oriented such that the N-terminal SH2 domain is on the left-hand side of the figure, the C-terminal SH2 domain is on the right-hand side of the figure and the inter-SH2 domain region is in the middle, dropping toward the bottom of the figure. Secondary structural elements 3 0 are labeled according to the convention for SH2 domains.

2 0 An a-carbon trace of the peptide is included. All elements are labeled in ZAP-N; in ZAP-C, only the central sheet and helices are labeled. Termini of the protein and peptide are denoted by N and C. Loop regions are named for the secondary elements which they connect, the BC loop connects strands B and C. The N terminus of the peptide is at the right-hand side of the figure. The peptide consists of 19 3 5 residues, starting at residue 48 of the mature C subunit of the T cell receptor (TCR).

Phosphotyrosines are at relative positions 4 and 15. Definition of least squares planes fitted to the main chain atoms of each pYXXL motif generates a pair of planes at an angle of 1200. Due to the staggered orientation of the SH2 domains, the pYXXL motifs are separated by an "S"-shaped segment of peptide. This sequence contains nearly one full turn of an (a-helix between residues C -9- Asn 8 and C Arg 12. Pockets for each pY and pY+3 residue are visible. It is notable that the Nterminal rl residues contribute to the enclosure of pTyr 4. The figure was generated with Sybyl (Tripos). An electron density map of the region near the interface between the two SH2 domains may be calculated with 21Fol-IFcl coefficients for data between 15.0 and 1.9 A, contoured at 1.0 s.

FIG. 18 The BC loop, from p B5 to P C3, of ZAP-N may be superimposed with the corresponding residues of the Lck SH2:middle T complex 2 0 and the relative position of the BC loops examined when the structures are fitted according to secondary structural elements. Superimposition of 1 0 the backbone atoms of the loops results in an r.m.s. deviation of 0.65 A. Similar results are observed with the BC loop of ZAP-C. In complexes of phosphopeptides with isolated SH2 domains, the BC loop contributes nearly half of the direct hydrogen bonds to the phosphate group. For both SH2 domains of ZAP-NC, the BC loop is extended such that several waters are mediating contact between the loop and the phosphate group. An extended conformation is also 1 5 observed for uncomplexed SH2 domains, and has been reported in complexes with peptides in which the phosphate group is replaced by a phosphonate.

1 4 The loop is repositioned via a hinged motion about the residues at 0 B5 and p C3. The BC loop of ZAP-C is more extended; ZAP-N experiences hindered motion about BC due to its interactions with ZAP-C.

S 2 0 FIG. 2 Sequence alignments [SEQ ID NOS 21 25] for selected SH2 domains.

3 3 Boxed areas indicate segments used for measuring "full" backbone r.m.s. deviation; unboxed areas are excluded from the calculation due to the presence of gaps for one or more of the sequences.

Notation below the alignments indicate structurally conserved regions, and use the previously reported nomenclature; 2 0 these regions were used for the "core" r.m.s. deviation calculation.

2 5 Thin-lined boxed areas within ZAP-N and ZAP-C indicate the secondary structural elements in ZAP-NC. Src avian Src; Lck human p56-Lck; Syp-N N-terminal SH2 of murine Syp phosphatase (PTP1D); ZAP-N(C) N- or C- terminal SH2 of human FIG. 3 Phosphotyrosine binding sites. The phosphotyrosine residues are oriented in a similar 3 0 fashion in each figure to facilitate direct comparison, a, Selected residues for the pTyr 4 association with ZAP-C. Direct hydrogen bonds to the phosphate group of i pTyr 4 are indicated by dashed lines. Crystallographic waters are indicated as spheres; waters labeled 551, 555, and 556 make bridging contacts between the phosphate and the SH2 domain, water 622 forms a bridge to C1. b, Selected residues in close association with C pTyr 15. As in a, dashed lines 3 5 indicate direct hydrogen bonds to the phosphate group. Tyr 238 and Lys 242 from ZAP-C complete the hydrogen-bonding network of the phosphate. Waters are represented as spheres; all of them are involved in salt-bridging the phosphotyrosine to the SH2 domains. Several residues that form the pocket have been omitted for clarity, c. The interface between the SH2 domains involves an extensive network of hydrogen bonds. Interactions involving C pTyr 10 have been described elsewhere herein. Several hydrophobic contacts also exist, the most provocative of these is the protrusion of Arg 41 (ZAP-N BC loop) into a small hydrophobic depression formed by Phe 229 (ZAP-C P Tyr 238 (ZAP-C aB), and the side chain of Thr 227 (ZAP-C EF loop). Arg 41 also has three hydrogen-bonding contacts to ZAP-C. This is the first of three residues in the BC loop of ZAP-N that form an artificial parallel sheet with strand F in ZAP-C. Only one of the three hydrogen-bonding contacts involves main chain atoms exclusively.

FIG. 4 Schematic view of ZAP-70 bound to the (1 subunit of the activated T cell receptor. Left: 1 0 Activation of T cells is initiated by association of the T cell receptor (TCR) with a peptide antigen bound to the major histocompatibility complex (MHC) on an antigen-presenting cell.

TCR-MHC association stimulates phosphorylation of T cell receptor subunits on tyrosines within the ITAMs (most likely by the Src family PTKs, Lck or Fyn). ZAP-70 binds to the o. phosphorylated ITAM via its tandem SH2 domains (amino acids 1-259) in an orientation such 1 5 that the N-SH2 domain binds to the C-proximal pYXXL motif and the C-SH2 domain binds the N-proximal pYXXL motif. Proposed positions of the other domains of ZAP-70, referred to as interdomain B (amino acids 260-310) and catalytic domain (amino acids 311-620) are illustrated. Two ZAP-70 molecules could bind to the activated TCR complex since the subunit is present as a disulfide-linked dimer. Right: Schematic representation of the complex between 20 the SH2 domains of ZAP-70 in complex with the doubly-phosphorylated i1 ITAM. The SH2 domains of ZAP-70 make extensive contacts with the (1 peptide. The primary determinants of binding are the phosphotyrosine and leucine residues of two pYXXL sequences within an ITAM.

The structure reveals a unique binding pocket for the pY of the C-proximal pYXXL motif in the interface between the two SH2 domains. In addition, the crystal structure reveals that 2 5 interdomain A forms a coiled-coil helical structure. This domain may. participate in positioning i* the two SH2 domains for association with ITAMs, and in communicating structural changes to interdomain B and/or the kinase domain upon receptor engagement.

FIG. 5 depicts a binding curve of a doubly-phosphorylated C-1:ZAP-NC complex, with 3 0 associated Scatchard plot of the data, as determined by fluorescence polarization.

FIG. 6 depicts the ZAP-NC: 1 complex encased in a gridded box for receptor site mapping.

Only the backbone of ZAP-NM and the peptide are illustrated. Colors may be indicated as follows: red and blue for oxygen and nitrogen atoms, respectively; yellow for carbon atoms of 3 5 the peptide; cyan, orange and green for N-terminal SH2 domain, the inter-SH2 spacer and the C-proximal SH2 domain carbon atoms, respectively. Note that the box encompasses space that is occupied by the peptide, as well as several interfacial regions of the SH2 domains.

11 FIG. 7 depicts a representative site contour map of ZAP-NC. FIG. 7A A selected region of the receptor map for ZAP-NC plus an amino cation probe contoured at -10 kcal/mol. A pocket on the protein surface is indicated by a solvent-accessible surface. FIG. 7B The individual amino acids that are in close proximity to the contour map are shown explicitly. The position of the contour indicates that strong interactions will be achieved between a hydrogen-bond donating moiety and the main chain carbonyl oxygens of Arg 192, Glu 194, and Thr 197, as well as the side chains of Gin 195 and Tyr 198.

FIG. 8 depicts a computer system.

FIG. 9 depicts storage media of this invention.

Detailed Description of the Invention 1 5 A. Introduction: The immune response is mediated by signalling through the T cell receptor complex with which ZAP-70 is associated T cell recognition of antigen-presenting cells initiates a cascade of intracellular processes that ultimately result in changes in gene expression, the production of secreted mediators, and cellular proliferation. 1, 2 This recognition is mediated by the T cell receptor (TCR), which consists of the antigen binding subunits a and 13, the CD3 complex of 5-E and -E heterodimers, and the C homodimer. With the exception of a and 1, the intracellular portion of each subunit .0 includes one to three peptide sequences that contain the motif YXX(L/I)X( 7 -8)YXX(L/I), where X is variable. 3 Following receptor stimulation, these immunoreceptor tyrosine activation 2 5 motifs, or ITAMs, become phosphorylated on tyrosine residues and in this modified form, provide binding sites for downstream signaling proteins.

The TCR has no intrinsic protein tyrosine kinase (PTK) activity, however members of both the Src family and the SYK/ZAP-70 family of PTKs are implicated in the functioning of antigen 3 0 receptors.

4 Current evidence indicates that Src family kinases phosphorylate the ITAMs of the TCR. 4 ZAP-70 then associates with the doubly-phosphorylated ITAMs of the C and CD3 E chains through its SH2 domains 5 and is itself phosphorylated during early T cell activation. 6 associated protein) is a 70 KDa protein tyrosine kinase that is expressed exclusively in T cells and NK cells.

7 ZAP-70 is known to play a critical role in T cell activation. Genetic 3 5 alterations in the ZAP-70 gene that cause loss of expression of ZAP-70 in humans prevent antigen activation of CD4 T cells, inhibit maturation of CD8 T cells, and lead to severe combined immunodeficiencies. 8, 9 ZAP-70 binding to the TCR is believed to be essential for signal transduction since peptides that block the association of ZAP-70 with the C chain also 12 inhibit T cell signaling events.

10 For these reasons, ZAP-70 is an ideal target for the development of novel immunosuppressive therapies.

The first 259 residues of ZAP-70 consist of two SH2 domains that are connected by a residue segment and are followed by a second connecting region and a catalytic domain.

7 SH2 domains consist of approximately 100 amino acids. Their role in the specific recognition of tyrosine-phosphorylated proteins is integral to a variety of intracellular signaling events (recently reviewed in 11, 12 Several SH2 domains have been demonstrated to retain the ability to bind with high affinity to short peptides that contain phosphotyrosine (pY) when 1 0 expressed as isolated proteins. Selectivity for isolated SH2 domains is dependent upon recognition of residues immediately C-terminal to the phosphorylated tyrosine The three-dimensional structures of several isolated SH2 domains (both liganded and Sunliganded), 13 14 as well as one SH3-SH2 complex 1 5 and one SH3-SH2-SH3 protein, 1 6 have been determined by X-ray crystallography or NMR. In order to bind to the TCR, ZAP 1 5 requires that both of its SH2 domains are present and functional and that both tyrosines within the ITAM are phosphorylated.

17 19 B. Structure Determination 2 0 Despite the pivotal role of ZAP-70 in the immune response, nothing was known of the threedimensional architecture by which the tandem SH2 region of ZAP-70 engages the ITAMs in the interactions required for its biological activity. X-ray crystallographic techniques could in principle address such issues. However; notwithstanding the key biological functions mediated by ZAP-70 and other ZAP family members such as SYK, there have been no reports disclosing 2 5 that suitable crystals had been or could be obtained, let alone reports disclosing any x-ray Scrystallographic data or other information concerning the three-dimensional structure of any tandem SH2 domain. Even in the event that crystals had been obtained, then-available threedimensional structural data relating to individual SH2 domains would not have been useful in solving the tandem structure, at least in part, because it wouldn't have permitted least squares minimization techniques necessary for structure refinement.

Nonetheless, we have succeeded in producing a protein containing the peptide sequence of the region of human ZAP-70 spanning both the more N-terminal SH2 domain, the more C-terminal SH2 domain and the linking region and have obtained crystals of that protein, crystallized in unliganded form and in complexes with various ligands. Using such materials, we have solved the three-dimensional structure of ZAP-NC using x-ray diffraction techniques. In view of our successes as disclosed herein, it can now be said that proteins comprising tandem SH2 domains, especially those of ZAP family members such as ZAP and SYK, can be produced in stable form, purified, and crystallized whether in complexes with a ligand or not, and that their 13 three-dimensional structures can be determined, all using materials and methods such as disclosed herein.

Materials As mentioned elsewhere, ZAP-NC is one of a number of proteins that contain two src-homology 2 (SH2) domains. The presence and boundaries of an SH2 domain in a protein sequence can be identified by using a computer alignment program that identifies amino acid sequence homology to a known SH2 domain. Generally, the SH2 domain (amino acids between 140-255) of Src are used for such analyses, but SH2 domains from other proteins can be used as well. The alignment 1 0 method typically used by such programs is the Needleman-Wunch alignment. See "A General Method Applicable to the Search for Similarities in the Amino Acid Sequence of Two Proteins." Needlman, Wunch, C.D. J. Mol. Biol. 1970, 48, 443-453. SH2 domains have been identified in a large and growing number of proteins, some of which contain multiple SH2 domains. For example, tandem SH2 regions are present in human ZAP-70 (spanning amino 1 5 acids 1-259), human SYK (spanning amino acids q PLCy, PI3K. rasGAP, SH-PTP1, and SH-PTP2.

We expressed ZAP-NC as a glutathione-S-transferase (GST) fusion protein. The cDNA encoding residues 1-259 from human ZAP-70 10 was cloned into the pGEX2T expression vector 41 and 2 0 transformed into E. coli BL21 or E. coli B834. The resulting construct produced a fusion protein of GST-ZAP-NC linked by a polypeptide segment containing the sequence -LVPRGSwhich comprises a thrombin cleavage site. The selenomethionyl (SeMet) ZAP-NC was produced using the auxotrophic strain of E. coli 834 42 with the selenomethionine replacing methionine in a defined media. The GST-ZAP-NC fusion protein was isolated using glutathione agarose and 2 5 then cleaved with thrombin. Cleavage yields two polypeptides, the GST and ZAP-NC. The ZAP-NC S°polypeptide contains two extra amino acids (Gly-Ser) at the amino terminus from the linker segment of the pGEX2T expression vector. These two extra amino acids were shown to have no functional effect on ZAP-NC binding to peptide ligands. ZAP-NC was separated from GST by binding ZAP-NC to a phosphotyrosine agarose column and eluting with a salt gradient.

3 0 Subsequently, ZAP-NC was further purified on a phenyl sepharose column. ZAP-NC:peptide ligand complexes were formed by mixing two-fold excess of peptide and purified ZAP-NC, then subjecting the mixture to chromatography using a superdex 75 gel filtration column. Fractions containing the purified ZAP-NC:peptide complex were combined and used for subsequent crystallization experiments.

Other ZAP-NC proteins may also be used, including ZAP-NC proteins truncated at the Nterminus and/or C-terminus to contain just the SH2 homology boundaries. Likewise, the protein may be extended at the C-terminus to include additional amino acids extending to include additional domains (spacer B) up to the entire ZAP-70 protein (amino acids 1-620).

14 Additionally, other tandem SH2 regions, especially from human and non-human ZAP family members, including proteins such as human SYK, may be prepared and used in analogous fashion to that described herein. It should further be appreciated that other expression systems may be readily employed. For instance, the tandem SH2 protein may be produced in E. coli using T7, maltose-binding protein fusion (MBP), with epitope tags (His6, HA, myc, Flag) included or cleaved off. Baculoviral expression may be used, e.g. using pVL1393 or derivatives, for tandem SH2 protein, fused (or not) to epitope tag or fusion partner such as GST. Conventional materials and methods for expression in mammalian, yeast or other cells may also be used.

1 0 Peptide ligands for co-crystallization with ZAP-NC or other tandem SH2 proteins may be prepared using conventional methods, containing peptide sequences based on naturally occurring ITAM sequences such as ITAM sequences derived from the T cell receptor 1, 12, 3, E, yor 6 subunits or from the p or y subunits of the IgE receptor, for example. In most cases such ligands will contain the 15 amino acid minimal ITAM sequence YXXLXXXXXXXYXXL [SEQ ID NO 1] and S 1 5 may contain additional amino acids at either or both the N- and C-termini. The N-terminus may comprise a free amino group or may be modified, e.g. amidated. Likewise, the C-terminus may be a free carboxylate or may be amidated or otherwise modified. Tyrosines may (each) be phosphorylated (pTyr). Alternatively, difluourophosphonoTyr, phosphonomethyl phenylalanine, hemi-phosphorylated Tyr, or other pTyr mimetics may be used in place of pTyr.

2 0 The ligand may contain amino acid replacements, insertions or deletions with respect to a **e naturally occurring ITAM sequence. Furthermore, hybrid peptide-nonpeptide ligands and nonpeptide ligands may also be used. Examples of such ligands are depicted in Table 1.

Crystallization 2 5 Crystallization experiments were conducted using a sparse matrix screening approach, in the case of ZAP-NC crystals, beginning with a Crystal Screen 1 kit (Hampton Research, Riverside, CA). Crystals containing SYK-NC were obtained as described below. In the case of ZAP-NC, best results were obtained using protein stabilized in 0.5 M NaCI, followed by removal of salt by dialysis prior to the crystallization experiments. Special handling of that sort was not 3 0 necessary for SYK-NC, but may be useful for other tandem SH2 containing proteins.

For example, crystals of ZAP-NC complexed with the doubly-phosphorylated 19meric 1 ITAM peptide (Ligand 5, Table 1) were grown from polyethylene glycol (PEG) 4000. The structure was elucidated by multiple isomorphous replacement at 1.9 A resolution. It was not possible to 3 5 solve the structure by molecular replacement alone using coordinates for previously determined SH2 domains. This was due to the low sequence identity with other SH2 domains and between the two ZAP domains, as well as to the presence of the 65 residue interdomain region.

The details of crystallization, data collection, multiple isomorphous replacement (MIR), and refinement are described below.

15 Specifically, ZAP-NC complexed with doubly-phosphorylated j peptidle was concentrated to mg/mi in 20mM Tris, pH 8.5, 200mM sodium chloride and 20mM dithiothreitol. The complex was treated with 4mM trimethyllead acetate (TML). Crystals were obtained by vapor diffusion in hanging drops containing 13.5 mg/mI complex and 10% PEG 4000, 50mM sodium citrate, 100mM ammonium acetate, 0.005% sodium azide and 20mM dithiothreitol, pH 6.2, over reservoirs of 20% PEG 4000 and 20mM dithiothreitol. The crystals are monoclinic (P2 1 a=50.1 1, b=63.37, C=54.00 A, j3 =1 14.440) with one molecule per asymmetric unit.

1 0 In other experiments, using similar conditions, we were also able to obtain crystals of ZAP-NC complexed with dloubly-phosphorylated j peptide which were found to contain two molecules per asymmetric unit. Those crystals are also monoclinic (P21, a=65.17, b=62.00, c=78.67 1 5 As described in detail in Experimental Example Ill and crystals were also obtained under similar conditions of liganded and unliganded ZAP-NC and SYK-NC proteins.

TABLE 1: Various Tandem SH2 Ligands IgE -yTAM l9mer [SEQ ID NO 21 Ac.Asp.Gly.Val.pTyr.Thr.Gly.Leu.Ser.Thr.Arg.Asn.Gln.- Glu.Thr.pTyr.Glu.Thr.Leu.Lys.NH2 IgE yTAM i5mer [SEQ ID NO 3] Ac.pTyr.Thr.Gly.Leu.Ser.Thr.Arg.Asn.Gln.Glu.Thr.pTyr.Glu.Thr.Leu.NH2 5 Ac-(py 4 1 5 1 IgE yTAM 25mer [SEQ ID NO 41 Ac.Asp.Gly.Val.pTyr.Thr.Gly.Leu.Ser.Thr.Arg.Asn.Gln.- Glu.Thr.pTyr.Glu.Thr.Leu.Lys.His.Glu.Lys.Pro.Pro.Gn.OH Ac-[py 6 1 7 IgE -yTAM 27mer [SEQ IDNO Ac.Lys.Ser.Asp.Gly.Val.pTyr.Thr.Gly.Leu.Ser.Thr.Arg.Asn.Gln.- Glu.Thr.pTyr.Glu.Thr.Leu.Lys.His.Glu.Lys.Pro.Pro.Gn.OH [py 4 15 ]TCRCTAM 1 (l9mer 1) [SEQIDNO6] Ac.Asn.Gln.Leu.pTyr.Asn.Glu.Leu.Asn.Leu.Gly.Arg.Arg.Glu.- Glu.pTyr.Asp.Val.Leu.Asp.N H2 16 Ac-py[ 3 ,15I-Nle[11'I-NH2 (l9mer 2) [SEQ ID N07] Ac.Gly. Leu.pTyr.Asn.Glu.Leu.GinLys.Asp.Lys.Nle.Ala.Gu Ala.pryr.Ser.Gu.lle.Gly.NH 2 Ac-py[ 4 1 5 ]-TCR 3 [SEQ IDNO 8] Ac.Asp.Gly.Leu.pTyr.Gn.Gly.LeuSerThr.Ala.Th r.Lys.Asp.- Thr.pTyr.Asp.Ala.Leu.His.NH2 Ac-[Phe(p-l) 3 1-TCRjTAM(1 )-NH2 [SEQ IDNO 9] 0 N N ~N PTI r.Asn.Glu.LeuAsn.Leu.Gly.ArgArgGluGlupTyrAspValuAsp.NH set H 2 N 0 S(9) Ac-F2Pmp[ 4 15] j NH 2 [SEQ ID NO 101 :.:Ac.Asn.Gln.Leu.F2Pmp.Asn.Gu.Leu.Asn.Leu.Gy.Arg.Arg.Gu- GIu.F2Pmp.Asp.Val.Leu.Asp.NH 2 a* (10) IgE-y analog [SEQ ID NO 11] Ac.Asp.G Iy.Val. pTyr.Th r. ly.Leu.Ala.Ala.Ala.Ala. pTyr. GI uThr. Leu. Lys. NH 2 (11)o c-pY-Thr-nmGly-nmLeu.NH 2 [E DN 3

OH

HO 0 0 0 HI H 0HO" CH, 0 Notes: Ligands (10) and (11) co-crystallized with ZAP-NC. Of those, and formed dimeric crystals, containing two ligand:ZAP-NC complexes per asymmetric unit. and (10) formed crystals containing one ligand:ZAP-NC (containing lead) per asymmetric unit. co-crystallized with SYK-NC, with several molecules of complex per asymmetric unit.

17 The standard triple and single letter codes for abbreviating the names of amino acids are used, Alanine (Ala, Arginine (Arg, Asparagine (Asn, Aspartic Acid (Asp, Cysteine (Cys, Glutamine (Gin, Glutamic Acid (Glu, Glycine (Gly, Histidine (His, Isoleucine (lie, Leucine (Leu, Lysine (Lys, Methionine (Met, Phenylalanine (Phe, Proline (Pro, Serine (Ser, Threonine (Thr, Tryptophan (Trp, Tyrosine (Tyr); and Valine (Val, The following terms are also abbreviated: phosphotyrosine (pTyr, pY), difluorophosphonomethylphenylalanine (F2Pmp), Fluorenylmethyloxycarbonyl (Fmoc), N-methyl (nm) and acetyl (Ac) Data Collection Diffraction data were collected with an Rigaku R-AXIS II area detector with graphite monochromated Cu Ka X-rays. Diffraction data were collected as 20 oscillation images and reduced to integrated intensities with DENZO.

4 3 Scaling parameters for each image were calculated with ROTAVATA 4 4 and applied with AGROVATA.

4 4 Data sets were collected for all SYK and ZAP crystals (with and without bound ligands) at -160°C except for those collected at room temperature for crystals containing ZAP-NC protein containing lead.

e 1 0 MIR Analysis and Refinement SeMet ZAP-NC was crystallized with TML under the same conditions and data collected. Positions of the lead and selenium atoms were determined from the difference Patterson function.

Anomalous dispersion measurements were included for both datasets. Heavy atom parameters were refined, and phases were obtained at 2.8 A with the program MLPHARE.

4 4 The MIR phases 1 5 were improved with the program DM 4 4 with a combination of solvent flattening/histogram mapping and phase extension to 2.0 A. Electron density maps with MLPHARE and DM phases were calculated, and the polypeptide chain model was built with the program 0 4 5

SIGMAA

4 4 was used to perform several cycles of phase combination using partial model and experimental phases. Least squares refinement with simulated annealing was done using X-PLOR.

4 6 The 20 current model has all residues from Asp 3 to Asn 256 of the protein, all 19 peptide residues of zeta-1, and 113 water molecules, plus one lead and three selenium atoms. TML is bound to Cys 117. See Table 2.

Structural Coordinates, Their Storage and Use 2 5 The structural coordinates of crystalline compositions of this invention may be obtained as described in detail herein. By way of example, Appendix I, Appendix II and Appendix III set forth the structural coordinates, in PDB format, for crystalline compositions comprising ZAP- NC: 1 "monomer" (one molecule of complex per unit cell), ZAP-NC: 2, and ZAP-NC: i1 "dimer" (two molecules of complex per unit cell).

This invention encompasses crystalline compositions containing a ZAP family protein having a region characterized by structural coordinates set forth in Appendices I, II or III, or by coordinates having a root mean square deviation therefrom of less than about 1.5 A, preferably 18 less than about 1 A, and even more preferably less than about 0.5 A, with respect to backbone atoms of amino acid residues listed there.

TABLE 2: Statistics for data collection, phase determination, and refinement for ZAP-NC: 1 "monomer" Data Collection Resolution Reflections Completeness Rsym Rc FOM Phasing Power (20-2.8 A) TML 25 2.5 15,506 98.3 6.3 SeMet 25 2.9 23,978 98.9 4.9 0.71 0.50 1.38

TML

Refinement Model 272 residues, 113 water molecules, 1 lead, 3 selenium atoms Resolution Reflections R-value Free R-value" Rms deviations (F 2) Bonds Angles (0) 10 1.9 23,697 20.9 25.5 0.006 1.58 'Notes: Rsym I li I i x 100 Rc Y IIFph Fpl Fhcalc I/ IFph Fpl for centric reflections.

Phasing power, Fh/E where E rms lack of closure error.

FOM Figure of merit Rvalue IIFobsi-IFcalcll/ IFobsIx 100.

subset of data was excluded from refinement and used for free R-value calculation. All data with F>2a were used for refinement.

5 As practitioners in this art will appreciate, various computational analyses may be used to determine the degree of similarity between the three dimensional structure of a given protein (or a portion or complex thereof) and ZAP-NC or another ZAP family protein or portion or complex thereof such as are described herein. Such analyses may be carried out with commercially available software applications, such as the Molecular Similarity application of 1 0 QUANTA (Molecular Simulations Inc., Waltham, MA) version 3.3, and as described in the accompanying User's Guide, Volume 3 pgs. 134 135.

The Molecular Similarity application permits comparisons between different structures, different conformations of the same structure, and different parts of the same structure. The 1 5 procedure used in Molecular Similarity to compare structures is divided into four steps: (1) load the structures to be compared; define the atom equivalences in these structures; (3) perform a fitting operation; and analyze the results.

19 Each structure is identified by a name. One structure is identified as the target the fixed structure); all remaining structures are working structures moving structures). Since atom equivalency within QUANTA is defined by user input, for the purpose of this invention we define equivalent atoms as protein backbone atoms Ca, C and 0) for all conserved residues between the two structures being compared and consider only rigid fitting operations.

When a rigid fitting method is used, the working structure is translated and rotated to obtain an optimum fit with the target structure. The fitting operation uses a least squares fitting algorithm that computes the optimum translation and rotation to be applied to the moving 1 0 structure, such that the root mean square difference of the fit over the specified pairs of equivalent atom is an absolute minimum. This number, given in angstroms, is reported by

QUANTA.

For the purpose of this invention, any set of structural coordinates of a ZAP family protein, 1 5 portion of a ZAP family protein or molecular complex thereof that has a root mean square deviation of conserved residue backbone atoms Cax, C, O) of less than 1.5A when superimposed-using backbone atoms-on the relevant structural coordinates of a protein or complex of this invention, e.g. the coordinates listed in Appendix I, Appendix II or Appendix Ill, are considered identical. More preferably, the root mean square deviation is less 20 than 1.OA. Most preferably, the root mean square deviation is less than The term "root mean square deviation" means the square root of the arithmetic mean of the oe**°squares of the deviations from the mean. It is a way to express the deviation or variation from a trend or object. For purposes of this invention, the "root mean square deviation" defines the 25 variation in the backbone of a protein from the backbone of a protein of this invention, such as ZAP-NC, as defined by the structural coordinates of Appendix I, Appendix II or Appendix III and described herein.

The term "least squares" refers to a method based on the principle that the best estimate of a value is that in which the sum of the squares of the deviations of observed values is a minimum.

In order to use the structural coordinates generated for a crystalline substance of this invention, e.g. the structural coordinates of ZAP-NC, 1, 2, or the various complexes as depicted in Appendix I, Appendix II or Appendix III, it is often necessary or desirable to display them as, or convert them to, a three-dimensional shape, or to otherwise manipulate them. This is typically accomplished by the use of commercially available software such as a program which is capable of generating three-dimensional graphical representations of molecules or portions thereof from a set of structural coordinates.

20 By way of illustration, a non-exclusive list of computer programs for viewing or otherwise manipulating protein structures include the following: Midas (University of California, San Francisco) MidasPlus (University of California, San Francisco) MOIL (Univeristy of Illinois) Yummie (Yale University) Sybyl (Tripos, Inc.) Insight/Discover (Biosym Technologies) MacroModel (Columbia University) Quanta (Molecular Simulations, Inc.) Cerius (Molucular Simulations, Inc.) .'.Alchemy (Tripos, Inc.) e LabVision (Tripos, Inc.) 15 Rasmol (Glaxo Research and Development) Ribbon (University of Alabama) NAOMI (Oxford University) Explorer Eyechem (Silicon Graphics, Inc.) Univision (Cray Research) 20 Molscript (Uppsala University) Chem-3D (Cambridge Scientific) Chain (Baylor College of Medicine) O (Uppsala University) GRASP (Columbia University) 25 X-Plor (Molecular Simulations, Inc.; Yale University) Spartan (Wavefunction, Inc.) Catalyst (Molecular Simulations, Inc.) Molcadd (Tripos, Inc.) VMD (University of Illinois/Beckman Institute) Sculpt (Interactive Simulations, Inc.) Procheck (Brookhaven National Laboratory) DGEOM (QCPE) RE_VIEW (Brunel University) Modeller (Birbeck College, University of London) 3 5 Xmol (Minnesota Supercomputing Center) Protein Expert (Cambridge Scientific) HyperChem (Hypercube) MD Display (University of Washington) PKB (National Center for Biotechnology Information, NIH) 21 ChemX (Chemical Design, Ltd.) Cameleon (Oxford Molecular, Inc.) Iditis (Oxford Molecular, Inc.) For storage, transfer and use with such programs of structural coordinates for a crystalline substance of this invention, a machine-readable storage medium is provided comprising a data storage material encoded with machine readable data which, when using a machine programmed with instructions for using said data, e.g. a computer loaded with one or more programs of the sort identified above, is capable of displaying a graphical three-dimensional representation of 1 0 any of the molecules or molecular complexes described herein. Machine-readable storage media comprising a data storage material include conventional computer hard drives, floppy disks, DAT tape, CD-ROM, and other magnetic, magneto-optical, optical, floptical and other media which may be adapted for use with a computer.

1 5 Even more preferred is a machine-readable data storage medium that is capable of displaying a graphical three-dimensional representation of a molecule or molecular complex that is defined by the structural coordinates of a protein of the ZAP family, e.g. ZAP-NC or SYK-NC, or portion thereof, and in particular, structural coordinates of ZAP-NC:1 or ZAP-NC: 2 set forth in Appendix I, Appendix II or Appendix III (or derivatives thereof such as zapNC-zl.pdb, 20 discussed elsewhere herein) a root mean square deviation from the backbone atoms of the amino acids of such protein of not more than 1.5 A. An illustrative embodiment of this aspect of the invention is a conventional 3.5" diskette, DAT tape or hard drive encoded with a data set, preferably in PDB format, comprising the coordinates of Appendix I, Appendix II or Appendix Ill.

In another embodiment, the machine-readable data storage medium comprises a data storage material encoded with a first set of machine readable data which comprises the Fourier transform of the structural coordinates set forth in Appendix I, Appendix II or Appendix III (or again, a derivative thereof), and which, when using a machine programmed with instructions for using said data, can be combined with a second set of machine readable data comprising the X-ray diffraction pattern of a molecule or molecular complex to determine at least a portion of the structural coordinates corresponding to the second set of machine readable data.

FIG. 8 illustrates one version of these embodiments. The depicted system includes a computer A comprising a central processing unit a working memory which may be, RAM (random-access memory) or "core" memory, mass storage memory (such as one or more disk drives or CD-ROM drives), one or more cathode-ray tube display terminals, one or 22 more keyboards, one or more input lines and one or more output lines all of which are interconnected by a conventional bidirectional system bus.

Input hardware B, coupled to computer A by input lines, may be implemented in a variety of ways. Machine-readable data of this invention may be inputted via the use of a modem or modems connected by a telephone line or dedicated data line L. Alternatively or additionally, the input hardware may comprise CD-ROM drives or disk drives D. In conjunction with the CRT display terminal, a keyboard may also be used as an input device.

Output hardware, coupled to computer A by output lines, may similarly be implemented by conventional devices. By way of example, output hardware may include a CRT display terminal for displaying a graphical representation of a protein of this invention (or portion thereof) using a program such as QUANTA as described herein. Output hardware might also include a printer, so that hard copy output may be produced, or a disk drive, to store system output for 15 later use.

.o :In operation, the CPU coordinates the use of the various input and output devices, coordinates data accesses from mass storage and accesses to and from working memory, and determines the sequence of data processing steps. A number of programs may be used to process the machine- 20 readable data of this invention. Examples of such programs are discussed in reference to the computational methods of drug discovery as described herein. Specific references to components of the hardware system of FIG. 8 are included as appropriate throughout the following description of the data storage medium.

25 FIG. 9A shows a cross section of a magnetic data storage medium 100 which can be encoded with a machine-readable data that can be carried out by a system such as a system of FIG. 8. Medium 100 can be a conventional floppy diskette or hard disk, having a suitable substrate 101, which may be conventional, and a suitable coating 102, which may be conventional, on one or both sides, containing magnetic domains (not visible) whose polarity or orientation can be altered magnetically. Medium 100 may also have an opening (not shown) for receiving the spindle of a disk drive or other data storage device 24.

The magnetic domains of coating 102 of medium 100 are polarized or oriented so as to encode in a manner which may be conventional, machine readable data such as that described herein, for execution by a system such as a system of FIG. 8.

FIG. 9B shows a cross section of an optically-readable data storage medium 110 which also can be encoded with such machine-readable data, or set of instructions, which can be carried out by a system such as a system of FIG. 8. Medium 110 can be a conventional compact disk read only 23 memory (CD-ROM) or a rewritable medium such as a magneto-optical disk which is optically readable and magneto-optically writable. Medium 100 preferably has a suitable substrate 111, which may be conventional, and a suitable coating 112, which may be conventional, usually of one side of substrate 111.

In the case of CD-ROM, coating 112 is reflective and is impressed with a plurality of pits 113 to encode the machine-readable data. The arrangement of pits is read by reflecting laser light off the surface of coating 112. A protective coating 114, which preferably is substantially transparent, is provided on top of coating 112.

In the case of a magneto-optical disk, coating 112 has no pits 113, but has a plurality of magnetic domains whose polarity or orientation can be changed magnetically when heated above a certain temperature, as by a laser (not shown). The orientation of the domains can be read by measuring the polarization of laser light reflected from coating 112. The arrangement of the 1 5 domains encodes the data as described above.

SC. Description of the Tertiary Structure of ZAP-NC:1i Solving the X-ray crystal structure of the tandem SH2 region of human ZAP-70 (ZAP-NC) in 20 complex with a 19meric peptide derived from the sequence of the first ITAM of the C subunit (41) of the TCR allowed us to conduct the first three dimensional characterizaiton of the .:protein:ligand complex. The complex involves an elaborate array of contacts between the peptide and both SH2 domains. The 65 residue inter-SH2 region exists as a coiled-coil of a-helices and assists in the formation of an interface between the two SH2 domains. The structure reveals the 25 startling fact that both SH2 domains contribute to the recognition of phosphotyrosine in the second pYXXL motif. This work reveals the first structural insights into the SYK/ZAP family of protein tyrosine kinases and provides the first view of an intracellular component of the TCR.

General Topology 3 0 The first 259 residue segment of ZAP-70 consists of two SH2 domains that are connected by a helical region. The overall fold is Y-shaped where the SH2 domains constitute each upper branch and the intervening 65 amino acid domain forms the stem. The fragment of ZAP-70 used in the crystal structure determination terminates before the kinase domain; therefore, we refer to the two SH2 regions as ZAP-N and ZAP-C, for ZAP N-terminal SH2 and ZAP C- 3 5 terminal SH2, respectively. There is high structural similarity between each of the SH2 domains and those previously reported, v-Src 13 and p56-Lck 2 0 Each of the individual ZAP SH2 domains possesses a central antiparallel P -sheet that is flanked by two a-helices. The inter-SH2 region begins as a P -strand that is a continuation of the central sheet of ZAP-N. This is followed by two antiparallel a-helices that intertwine to form a coiled-coil motif. The two 24 SH2 domains are in a partially staggered orientation; the central 3 -sheets are separated by about 29 A at an angle of ca. 520. This arrangement allows direct contact between the two SH2 domains, which is a requisite for peptide binding. The central 3 -sheet in ZAP-C is extended by distinct hydrogen bonds with several residues in ZAP-N, including some side chain contacts.

The C1 peptide is extended over both faces of the SH2 domains, straddles both central 3 -sheets, and makes extensive contacts with the protein surface. The binding orientation is head to tail, that is, the N-terminus of the peptide is in contact with the C-terminal SH2 domain. The Nterminal pYXXL segment of the peptide is bound to ZAP-C in a conformation similar to that seen 1 0 for singly-phosphorylated peptides bound to isolated SH2 domains.

2 0 2 1 The peptide segment that separates the two pYXXL motifs is largely in contact with ZAP-C. The C-terminal phosphotyrosine is bound in -a pocket that is formed by contributions from both SH2 domains.

The remainder of the second pYXXL motif is bound in a fashion similar to the first motif and in other complexes.

2 0 21 The ZAP SH2 domains All residues between Asp 3 Asn 256 are in good electron density, with no breaks. Residues Gin 2 to Leu 18 of the 1 peptide reside in good density, and the two terminal residues are in weak, but observable density. The nomenclature defined previously 2 0 for structural features of SH2 domains is used here for clarity. For the N-terminal SH2 domain (ZAP-N), the secondary structural elements are conserved but are slightly longer for strands A, E, F, and G. Due to the elongation of these strands, the sequence corresponding to a minor 3 -sheet (observed in previously reported SH2 domains) is an integral part of the central 3 -sheet in ZAP-N. More notably, helix A is longer by three residues, which extends the helix nearly a full turn. The C- 2 5 terminal SH2 domain of ZAP (ZAP-C) also possesses minor extensions to several secondary structural elements. Strands B, C, and E are longer by one or two residues. Helix A is also extended by a single residue. Strand F consists of only two residues and replaces the FB loop. The BC loop of ZAP-C is extended. There is very strong electron density for a number of structural waters, both within each SH2 domain and in all domain interfaces. The existence of a large 3 0 number of observed waters in the phosphotyrosine binding pockets is unique to ZAP-NC.

The Helical Interdomain A The inter-SH2 spacer begins in a type II reverse turn followed by a long p -strand that makes significant contact to strand A of ZAP-N, thus forming an extension to the central P sheet.

3 5 Hydrogen bonds exist between main chain atoms of Gin 111 and Tyr 12 and between Gin 111 and Ser 14. A water-mediated contact exists between the main chain atoms of Glu 109 and Tyr 12.

In addition to the hydrogen bonds, hydrophobic packing exists between Leu 108 and Tyr 12 and between Pro 110 and Phe 11.

25 This segment is followed by a five-turn a-helix (designated helix C) that extends away from both SH2 domains, forming the stem of the overall Y shape of ZAP-NC. This helix is followed by a turn consisting of Leu 133 and Glu 134. A second a-helix (helix D) curves around the axis formed by helix C. Helix D is distorted, with a break at Pro 147; a second break occurs at Ala 154 which precedes a short 310-helix that spans residues Thr 155 Met 161. Helices C and D both make several hydrophobic contacts to ZAP-C, most notably a p-stacked arrangement of Phe 115 (aC) to Trp 233. Several water-mediated hydrogen bonds exist between helix D and ZAP- C. These antiparallel helices form a coiled-coil structure, with direct contact between several hydrophobic residues forming its core.

For proteins that contain multiple SH2 domains, the region separating the two domains is highly variable in length. This region may be as short as 10-15 residues PLC-y1, SHPTP-1 and which would force the two SH2 domains into a back-to-back orientation. SYK has an inter-SH2 domain region which is of comparable length to that of ZAP, exhibits 68% sequence 1 5 identity to the helical spacer described here. It should maintain the same overall conformation observed in ZAP-NC. The tandem SH2 domains of the p85 subunit of phosphtidylinositol 3' kinase (PI 3-K) are connected by a significantly larger domain of 163 residues which has been predicted to also form a coiled coil of two antiparallel a-helices.

2 2 Binding Interactions for the Complexed 1 Peptide The ZAP-NC: 1 complex includes a 19 amino acid peptide that is phosphorylated on both tyrosine residues and is based on the first ITAM-containing segment of the human TCR chain o.oe (l1) which has the sequence NQLpYNELNLGRREEpYDVLD [SEQ ID NO 14]. For clarity, numbering for peptide residues begins at t Asn 1. The bound conformation of the (1 peptide is 25 largely extended, although nearly one full a-helical turn exists between residues Asn 8 and e* Arg 12. The backbone conformation for each pYXXL motif is similar to conformations observed for high affinity complexes of SH2 domains with singly-phosphorylated peptides.

2 0 21, 23 All residues of the 1 peptide, except for C Gly 10, are in contact with ZAP-NC. The area of the peptide-protein interface is over 1300A 2 Although this interface area is typical for proteino*.o protein interactions, the nature of the contacts is quite different from those generally observed.

2 4 For example, interfaces in antibody-antigen complexes and protease:proteininhibitor complexes usually contain few bridging waters. The interaction of ZAP-NC with 1 includes 21 bridging waters. The majority of contacts in protein-protein interfaces are usually S 3 5 classified as hydrophobic. In contrast, half of the contacts between ZAP-NC and 1 are due to direct hydrogen bonds. The total number of contacts observed is considerably larger than is observed for protein-protein structures of similar interfacial areas. Binding of phosphorylated peptides to individual SH2 domains has been described as reminiscent of a "socket and plug"; 2 1 this general arrangement is also present in ZAP-C and ZAP-N. Each socket consists of a highly 26 charged pocket that recognizes phosphotyrosine residues and a second pocket that prefers hydrophobic residues at the pY+3 position.

Binding of Motif-1 (-pYNEL-) is Exclusive to ZAP-C The amino terminal pYXXL motif of 1 is associated exclusively with ZAP-C. The first two residues of 1, C Asn 1 and Gin 2, are largely involved in intrapeptide interactions. The single contact between I Leu 3 and ZAP-NC, a hydrogen bond between the main chain carbonyl of t Leu 3 and NH1 of Arg 170, is typical for the pY-1 residue.

1 0 The pocket for t pTyr 4 is formed by residues from helix A, strands B, C, and D, and the BC loop. Hydrophobic contacts involve residues from 1 D, from which His 210, Tyr 211, and Leu 212 form one edge of the pTyr cavity. In addition, 5 Asn 1 and C Gin 2 of the peptide itself form hydrophobic contacts on the opposing side. The side chain of Leu 212 is twisted away from the pTyr ring and is packed against Trp 131 from a symmetry-related molecule. This neighboring 1 5 Trp, which constitutes the only intermolecular crystal contact with any (1 residue, is also in hydrophobic contact to C pTyr 4. Direct hydrogen-bonding contacts to the phosphate are made by only three residues. Arg 170 (aA) and Arg 190 (1 B) interact through their terminal nitrogens. Arg 192 is the only residue in the BC loop of sufficient length for direct hydrogen bonding to the phosphate group and interacts via its NE. The BC loop is extended; thus, the pTyr 2 0 binding region resembles a deep groove that continues toward the AA loop. The inclusion of the pY-2 and pY-3 residues as an integral part of the binding site results in the formation of a channel into which the pTyr protrudes. Five waters with very strong density and low temperature factors exist in this region and are part of a large hydrogen-bonding network.

As is typical for complexes with SH2 domains, 20 21, 23 the pY+1 and pY+2 residues are extended along the surface of the protein. The pY+1 residue (C Asn 5) makes contacts that are similar to those observed in the hamster middle T peptide in complex with the SH2 domains of Lck 2 0 and v-Src.

2 1 The pY+2 residue Glu 6) is directed away from the surface of the protein.

The pocket that surrounds C Leu 7 (pY+3) is very deep and is formed by residues from p D, the EF loop, helix B and the BG loop. Due to the size of this pocket, i Leu 7 is directly contacted by only 5 residues Tyr 211, lie 223, Gly 226, Gly 245, and Leu 246. The depth of this pocket is partially due to the presence of a leucine in helix B in ZAP-C that is occupied by a tyrosine in 3 5 many other SH2 domains.

2 3 Even in the absence of tyrosine, very strong density is observed for two waters near this site. The main chain of C Leu 7 is involved in a water-mediated hydrogen bond to the carbonyl oxygen of Pro 224. A second contribution to the overall shape of the pY+3 pocket is provided by a repositioning of the 0 turn in the EF loop. In complexes of isolated SH2 domains, this loop is involved in forming the steep solvent-exposed wall of the 27 pocket. In ZAP-C, the EF loop slides toward strand D to allow the remainder of the peptide to continue on its path toward ZAP-N.

Binding of Intermotif (-NLGRREE-) The peptide segment that separates the pYXXL motifs in C1 consists of seven amino acids which make the bulk of their contacts to ZAP-C. Since nearly a full turn of an c-helix begins at C Asn 8 and continues to C Arg 12, many contacts for this sequence are intrapeptide. Asn 8 makes a main chain hydrogen bond to the carbonyl oxygen of Gly 245 and C Arg 12 is involved in both direct and water-mediated hydrogen bonds to the backbone carbonyl of Glu 225 (EF loop); 1 0 two other water-mediated hydrogen bonds connect C Arg 12 to Gly 226 and Lys 228. The side chains of i Leu 9 and Arg 12 close off the pY+3 pocket of ZAP-C.

Two glutamate residues complete this segment of the C1 peptide, and because they are the pY-1 and pY-2 residues of the second pYXXL motif, they constitute the first contacts to ZAP-N. Glu 1 5 13 makes a main chain hydrogen bond to the backbone carbonyl of Asp 244. More interestingly, Glu 13 is involved in a direct hydrogen bond through its side chain carboxyl to the side chain amino group of Lys 242 (ZAP-C aB) which is an integral part of the phosphotyrosine pocket of the N-terminal SH2 domain. C Glu 13 also maintains van der Waals contact to Lys 242, as well as to Tyr 238 (ZAP-C aB) and the guanidinium group of Arg 17 (ZAP-N caA), which also contribute to the N-terminal pY pocket. Glu 14 maintains the characteristic pY-1 main chain carbonyl hydrogen bond to both terminal nitrogens of Arg 17 which, in turn, contacts the aromatic ring and phosphate group of pTyr Binding of Motif-2 (-pYDVL-) Requires Both Domains 2 5 Perhaps the most remarkable feature of the complex between ZAP-NC and C1 is the observation that the recognition pocket of pTyr 15 is composed of residues from both SH2 domains. This is the first report of a phosphotyrosine binding site of this nature. The impinging of ZAP-C on ZAP-N sequesters pTyr 15 in a deep tunnel. The side chain of C pTyr 15 makes van der Waals contacts to Arg 41 (BC loop), Val 47 (p His 58 (p and Pro 60 (P The side chain of Arg 17 is positioned over the aromatic ring of C pTyr 15, forming an amino-aromatic contact in addition to bridging the carbonyl of the pY-1 residue to the phosphate oxygens of C pTyr 15. The phosphate group is closely associated with the side chains of Tyr 238 (ZAP-C aB), Lys 242 (ZAP-C aB), Arg 17 and Arg 37 (p forming a total of six direct hydrogen bonds. Six water-mediated hydrogen bonds exist between the phosphate group and Arg 17 Cys 39 (p Leu 40 (BC loop), Arg 41(BC loop), and Lys 242 (ZAP-C aB). The relative importance of each residue in this interface may be determined through mutagenesis experiments. Four waters with strong electron density contribute to this extensive network; the presence of these waters may be a consequence of the intrusion of ZAP-C onto residues of the BC loop (vide infra).

28 In this arrangement, each oxygen of the phosphate group possesses its full complement of hydrogen-bonding partners.

As described for the first pYXXL motif, the pY+1 and pY+2 residues Asp 16 and Val 17) make contacts that are characteristic for these positions in other SH2 complexes.

2 0 21, 23 Leu 18 resides in a hydrophobic pocket that is of similar dimension to the pY+3 pockets observed in high affinity peptide complexes with Src family SH2 domains. A single watermediated hydrogen bond connects the main chain NH of Leu 18 to the carbonyl of Ala 72 on the EF loop. Contact to several hydrophobic residues is evident: P D contributes Phe 59; interaction 1 0 with the EF loop involves lie 71, Ala 72, Gly 73, and Gly 74; helix B presents Tyr 87; and the BG loop makes contact via Gly 93 and Leu 94. Asp 19 of 1 resides in weaker density and appears to form only one hydrogen bond from its main chain nitrogen to the carbonyl of Gly 93 (BG loop).

1 5 Interdomain Contacts Unlike the extensive contact area of C1 to ZAP-NC, the total interaction area between the ZAP-N and ZAP-C SH2 domains is small, measuring only ca. 200 A 2 The surface area of ZAP-N that is buried by ZAP-C and the inter-SH2 spacer is only about 400 A 2 the corresponding buried area in ZAP-C is not significantly larger. Total burial of ZAP-N in the full complex is 620 A 2 which 20 accounts for approximately 13% of the total surface area of the domain. Conversely, burial of ZAP-C is computed to be ca. 1000 A 2 which constitutes 20% of its total surface area. This difference is due to the presence of a large solvent accessible channel formed by the convergence of the convex side of the BC loop of ZAP-N, the FB loop and helix B of ZAP-C, and both helices of the inter-SH2 spacer. This irregularly shaped funnel has an approximate diameter of 5-7 A, and extends fully enclosed for ca. 12 A before flaring open for an additional 8 A. For the interface that is exclusively between the ZAP-N and ZAP-C domains, each SH2 domain contributes nine residues. Most of the contacts are through hydrogen bonds, and most of these are water-mediated. However, some van der Waals contacts do exist.

Given that the total interface that is exclusive to the two SH2 domains may not exist in the absence of the peptide, the inter-SH2 spacer is likely to stabilize the appropriate orientation for tandem binding by permitting only minor displacements through scissoring or wagging motions. In isoelectric focusing gels, uncomplexed ZAP-NC exists as multiple bands which collapse into a single band when the (1 peptide is added. This microheterogeneity observed with uncomplexed ZAP-NC is consistent with conformational variability.

Comparison to other SH2:phosphopeptide complexes Despite the low sequence identity between ZAP-N and ZAP-C, the similarity in overall fold is notable. Side chain positions are remarkably well-conserved between the two domains.

29 The overall backbone root-mean-square deviation is 1.07A the same measurement for ZAP-N or ZAP-C to Src family SH2 domains (individually) is typically 1.50 A, although the percentage of sequence identity is similar. As reported for previous structures of individual SH2 domains, 14 20, 21 the loop regions display the largest positional variance, most notably loops AA, BC, CD, and EF. The CD loops of both ZAP-N and ZAP-C have a large truncation relative to the SH2 domains of the Src family; this truncation is also evident from the sequences of a large number SH2 domains.

2 3 Although each pYXXL motif of i4 resides in a similar backbone conformation in the complex, the 1 0 orientation of the phosphotyrosines varies between ZAP-N and ZAP-C. The aromatic ring of r pTyr 4 superimposes remarkably well with the pTyr in both p56-Lck 2 0 and v-Src.

2 1 For C pTyr 15, however, the ring is repositioned 0.7 A toward the guanidinium of Arg 17 and slips 0.8 A away from strand D. This is likely to be due to the direction C1 takes as it moves into the ZAP-C domain, as well as the strong hydrogen-bonding interactions between the phosphate 1 5 group and Tyr 238 and Lys 242 on ZAP-C. Both pTyr pockets of ZAP-NC are large enough to permit the inclusion of several waters; this enlargement relative to other SH2 domains is due to the repositioning of the BC loop. The extended position for the BC (phosphotyrosine binding) loop observed for both SH2 domains of ZAP has been observed previously for uncomplexed SH2 domains and has been described as a hinge in the binding of tyrosine phosphorylated and phosphonated peptides.

1 4 21 Although the loop is reoriented, the internal conformation for the BC loop is strongly maintained.

S* The pY+3 pocket of ZAP-C is strikingly large compared to this site in other SH2 domains. This is due, in part, to repositioning of ZAP-C EF residues Pro 224 and Glu 225, as described 2 5 earlier. Aside from the absence of a Tyr in aB, the location of other side chains that form this pocket are notably similar to the corresponding sites in Lck and Src.

Also, in comparison with all other crystal structures of complexes of SH2 domains, a significant number of waters are present in ZAP-NC. Several are involved in bridging 3 0 phosphotyrosine to the protein. These intervening water molecules may contribute to the weak affinity of individual ZAP SH2 domains for phosphorylated ITAM ligands.

17 1 9 Additionally, a large number of buried or trapped waters exist in all of the various interfaces.

Biological Significance 3 5 The structure of the tandem SH2 domains of ZAP-70 in complex with a component of the C chain of the T cell receptor provides the first molecular glimpse into the intracellular machinery of the TCR (summarized in FIG. Several unique features of this structure suggest that each SH2 domain does not function as an independent module, and that interactions between the domains play a critical role in the recognition of phosphorylated ITAM sequences of the TCR by 30 In addition, the structural information is key to the interpretation of genetic and biochemical data and provides a framework for exploring the mechanism of action of The tandem SH2 domains of ZAP-70 exhibit strong selectivity for the phosphorylated C and E subunits of the TCR, while isolated SH2 domains from other proteins bind more promiscuously to many tyrosine phosphorylated proteins in total cell extracts.

5 Ligand binding and selectivity for isolated SH2 domains is mediated by recognition of a phosphotyrosine and several residues C-terminal to phosphotyrosine, particularly the hydrophobic residue at the pY+3 position 1 2 The high degree of selectivity of ZAP-70 for doubly-phosphorylated ITAM sequences appears to 1 0 be a consequence of multiple structural features. The distance between the two pYXXL motifs of the or E chain provides properly spaced partners for a pair of SH2 domains that are tethered in close association by an inter-SH2 coiled coil. Association of the pair of SH2 domains with the phosphotyrosines and other ITAM residues stabilizes a conformation that permits direct interaction between the domains and hence the formation of a deep pocket for sequestering one 1 5 phosphotyrosine at the domain interface.

While ZAP-NC exhibits high affinity for doubly-phosphorylated ITAMS and selectivity for the C .o and E chains, the individual SH2 domains of ZAP-70 have not been found to bind appreciably to phosphorylated peptides 5 In addition, ZAP-NC binds to monophosphorylated ITAM-based 20 peptides with affinities that are 100-1000 times lower than for the corresponding doublyphosphorylated ones.

17 1 9 25 Consequently, for high-affinity binding, both SH2 domains must cooperate, and two phosphotyrosine residues must be present and arranged appropriately.

The structural manifestation of this cooperativity and selectivity is also the most remarkable 0e feature of the complex between ZAP-NC and that is, the convergence of residues from both SH2 domains to enmesh pTyr To this point, it has been assumed that SH2 domains adopt their native fold when extracted from their natural molecular context and possess their full ability to recognize and bind to phosphorylated proteins.

12 14 We present structural evidence that the N-terminal SH2 domain of ZAP-70 if expressed in isolation, is incomplete. The groove-like nature of the pY pocket of ZAP-C suggests that this domain may also require contributions from neighboring domains or proteins.

From the crystal structure, we ascertain that the orientation adopted by ZAP-70 upon association with the TCR aligns ZAP-C with the N-proximal pYXXL motif of and ZAP-N with the C-proximal motif, as depicted in FIG. 4. We believe that this orientation may be important for positioning the catalytic domain of ZAP-70 for its activation and subsequent phosphorylation of downstream substrates in the signal transduction cascade.

31 All of the ITAMs of the TCR have a spacing of seven residues between the pYXXL motifs, except (2 which has a spacing of eight. In vitro binding experiments of ZAP-NC with synthetic phosphopeptides indicate that the binding hierarchy is 1 2 2 E C3.

2 5 These results suggest that one additional residue between the pYXXL motifs is tolerated. Conversely, a two amino-acid deletion in the corresponding region of E drastically reduces ZAP-70 binding and eliminates IL- 2 production.

1 7 Therefore, the distance between the two pYXXL motifs is important for association and signaling. In order to determine the relative contribution of each residue in the ITAM, experiments utilizing CD8-( 1 chimeras were conducted, in which each residue was systematically replaced with alanine. The results demonstrate that only the replacement of each 1 0 pY and pY+3 residue eliminates signaling completely, as measured by IL-2 production.

2 6 With the exception of these residues, the specific sequence of the ITAM is less important for selectivity than the distance between pYXXL motifs. More radical changes, such as the simultaneous replacement of multiple residues, are necessary to assess the contribution of ITAM sequences to selectivity.

As described earlier, the inter-SH2 region constrains the SH2 domains within a distance that permits association. However, because a significant portion of the antiparallel helices are directed away from the SH2 domains, this region may also be involved in inter- or intramolecular contacts, regulation of kinase activity, and/or receptor clustering. The evidence .o 20 that this domain forms a coiled coil of a-helices is of great interest, since these structural units are commonly involved in protein-protein interactions.

2 7 The inter-SH2 region of the p85 subunit of PI 3-K, which has been predicted to form a coiled coil, is necessary and sufficient for interaction of p85 with the p110 catalytic subunit of PI 3-K.

2 2 One intriguing possibility evident from our structure is that the ZAP interdomain is involved in regulation of 2 5 its kinase activity. The interdomain may inhibit catalytic activity directly or indirectly, and this inhibition might be relieved upon binding of the SH2 domains to the ITAM. Experiments with PI 3-K 2 5 and SYK 2 8 the PTK homologous to ZAP-70 support such a model. Addition of a phosphotyrosine-containing peptide that corresponds to Tyr 751 region of a known PI-3K SH2 binding site from the PDGFP receptor causes activation of P1 3-K in vitro.

2 9 Likewise, 3 0 phosphorylated ITAM peptides derived from the y subunit of the IgE receptor increase SYK kinase activity by 5-10 fold.

3 0 31 Another function for the inter-SH2 region may be to bind to proteins that either regulate ZAP-70 activity, such as Lck and/or Fyn, or that are substrates for ZAP-70. Tyrosine 126 in the inter-SH2 region is phosphorylated by Lck in vitro 3 2 and could be involved in interactions with other SH2 domain-containing proteins. Finally, the 3 5 inter-SH2 domain may be important for the intermolecular association between molecules which might occur in the activated TCR complex.

SYK should also exhibit these structural features in view of its functional similarities and sequence identity of 57% with respect to ZAP. SYK is expressed in several types of 32 hematopoietic cells and functions in mast cells and B cells by binding to ITAM sequences in the cytoplasmic domains of IgE and B cell receptors, respectively.

2 8 By comparing the ZAP-70 and SYK sequences, 3 3 most of the residues in ZAP-NC that contact pTyr 15 are conserved in the corresponding positions in SYK. The N-terminal SH2 domain of SYK does not bind to phosphotyrosine ligands or to phosphotyrosine affinity columns, 3 4 which suggests that, as in ZAP-NC, this phosphotyrosine site also requires the C-terminal SH2 domain in order to form a complete pocket. Doubly-phosphorylated peptides derived from the y ITAM of the IgE receptor induce SYK activation.

3 0 Our complex of ZAP-NC with (1 may therefore represent the conformation of the SH2 domains adopted in the activated kinase.

has emerged as an attractive target for the development of safe and potent immunosuppressive drugs. ZAP-70 has been shown to be required for T cell-mediated immune responses in humans, and loss of ZAP-70 does not affect other tissues.

8 Thus, ZAP antagonists would specifically inhibit T cells and avoid the toxicity of the currently used 1 5 immunosuppressive drugs, FK506 and cyclosporin 3 5 3 6 which target the more ubiquitously expressed protein calcineurin.

37 38 This protein phosphatase is required for T cell immune responses, as well as functions in several other tissues, and as a consequence, cyclosporin and FK506 cause serious side effects in the kidney and central nervous system which limit their application largely to pateients with organ transplant rejection.

36 New immunosuppressive drugs with less toxicity are needed to expand the routine use of such therapies to autoimmune o diseases.

One approach to inhibition of T cell activation is to develop small preferably having a molecular weight below about 1200, more preferably below about 750 and even more preferably below about 500), preferably non-peptidic, membrane permeant, molecules that S•bind to ZAP and prevent its association with the TCR. Such a compound may bind, preferably with high affinity, to either SH2 domain of ZAP-70 or to the inter-SH2 domain interaction. Our crystal structure reveals the molecular details of the three dimensional structure of ZAP and provides insights into its interactions with the TCR. The unique structural features of each SH2 3 0 ligand binding site and the unanticipated inter-SH2 association now can be exploited for structure-based design of highly specific small molecule ZAP ligands and structurally biased compound libraries.

D. Use of three-dimensional Structure of ZAP-NC in solving the structures of other tandem SH2 proteins Having solved the ZAP-NC structure we contemplate that other proteins containing two SH2 domains, especially ZAP family members, will have this unique binding pocket formed by interdomain association and that it can be exploited for the design of interfering compounds. The 33 protein currently considered to be most closely related to ZAP is SYK. (see figure of sequence alignment). Using the structure of ZAP-NC, a three-dimensional model of Syk-NC can be obtained through homology modeling. Prior to solving the ZAP-NC structure, this would have been difficult if not impossible since the sequence identity between the SH2 domains of Syk and SH2 domains of known structure is low and none of the previously solved SH2 domains contain two SH2 domains. Other currently known proteins with tandem SH2 domains are PLCy, P13K, rasGAP, SH-PTP1, and SH-PTP2. Additional proteins with two SH2 domains are expected to be discovered through genome sequencing or other cloning methods.

E. Use of Structure in Drug Discovery Utilization of the structure of the tandem SH2 domains of ZAP-70 in computeraided drug design (CADD) 1 5 The availability of the three-dimensional structure of the tandem SH2 domains of the protein .tyrosine kinase ZAP-70 (ZAP-NC) makes structure-based drug discovery approaches possible.

Structure-based approaches include de Novo molecular design, computer-aided optimization of lead molecules, and computer-based selection of candidate drug structures based on structural criteria. New peptidomimetic modules may be developed directly from the structure of the 20 peptide ligand by design or database searches for conformationally-restricted peptide replacements. Alternatively, structure-based lead discovery may be accomplished using the target protein structure stripped of its ligand. Multiple uncomplexed states of ZAP-NC can be generated by several methods to provide additional target conformations. The experimental coordinates and the resulting uncomplexed models can be subjected to techniques such as 2 5 receptor site mapping to identify sites of favorable interaction energies between the structure of the target protein and potential ligands or chemical moieties ("fragments" or "seeds"). Such evaluation may be followed by procedures such as fragment seed linking and growth. Fragment seed linking refers to methods for designing structures that contain "linked" "seeds", i.e.

chemical structures comprising two or more of the mapped moieties appropriately spaced to 3 0 reach the respective sites of favorable interactions. Growth refers to the design of structures which extend, based on receptor site mappping or to fill available space, a given molecule or moiety. Based on the receptor site mapping data, one may also select potential ligands from databases of chemical structures. Potential ligands, or suboptimal ligands, of whatever source, can be refined by using the receptor site maps to filter multiple ligand conformations and 3 5 orientations according to energetic preferences. Finally, in view of the high degree of sequence similarity to the tandem SH2 domains of p 7 2 SYk, the structure of ZAP-NC permits one to generate a high-quality model of Syk-NC by either knowledge-based homology template methods or iterative site-mutations followed by minimizations. The generated structure of Syk-NC may 34 then be treated as an additional protein target by the methods outlined above. These methods and their application to ZAP-NC are described in the sections that follow.

Peptidomimetics of the (1 peptide may be developed from the bound conformation of a peptide ligand by design, by searching databases for replacements of one or more peptide segments, or by enhancement of existing ligand-protein interactions by replacing a component moiety of a ligand with a substitute moiety capable of greater interaction with the target protein, whether through accessible protein contact points or by extrusion of otherwise sequestered waters). Knowledge of the bound conformation of a peptide can suggest avenues for 1 0 conformational restriction and peptide bond replacement. A less biased approach involves computer algorithms for searching databases of three dimensional structures to identify replacements for one or more portions of the peptide ligand, preferably non-peptidic replacement moieties. By this method, one can generate compounds for which the bioactive conformation is heavily populated, compounds which are based on particularly biologically 1 5 relevant conformations of the peptide ligand. Algorithms for this purpose are implemented in programs such as Cast-3D (Chemical Abstracts Service), 3DB Unity (Tripos, Inc.), Quest-3D (Cambridge Crystallographic Data Center), and MACCS/ISIS-3D (Molecular Design Limited).

These geometric searches can be augmented by steric searching, in which the size and shape requirements of the binding site are used to weed out hits that have prohibitive dimensions.

Programs that may be used to synchronize the geometric and steric requirements in a search applied to ZAP-NC include CAVEAT (University of California, Berkeley), HOOK (MSI), and ALADDIN (Daylight Software). All of these searching protocols may be used in conjunction with existing corporate databases, the Cambridge Structural Database, or available chemical databases from chemical suppliers.

In addition to the retention of potential pharmacophoric elements that are present in the peptide explicitly, the incorporation into a ligand structure of hydrogen-bond donating or accepting groups that can displace ordered water molecules usually provides a significant entropic gain that leads to a favorable free energy of binding. Such ordered waters are identifiable from the 3 0 structure, and other ordered waters may be located during computer simulations of a fully solvated structure, as described more thoroughly in a subsequent section.

Generation of alternate binding site conformations of the target protein may be desired in view of the flexibility of the phosphotyrosine binding region, the nature of the interface between the two SH2 domains, and overall, in view of the possibility of an induced fit, i.e., conformational changes in both ligand and protein upon binding. For example, the loop that connects p -strands B and C (the BC or phosphotyrosine binding loop) has been reported to act as a functional hinge in Src-family SH2 domains. In addition, charged residues in the phosphotyrosine binding pocket are capable of side chain reorientations. A variety of theoretical 35 methods, such as Metropolis Monte Carlo or molecular dynamics simulations (implemented in programs such as MCPro [Yale Univeristy], AMBER [UCSF], CHARMm [Harvard University], and GROMOS [ETH/Groningen]) may be used locally to generate Boltzmann distributions of uncomplexed states, and hence provide a set of additional conformations that are valid for molecular design. Alternate side chain reorientations can also be examined by Dead End Elimination and A* algorithms (University of Southhampton), by iterative systematic conformational searches of each side chain, or by comparison of each residue type to members of the Protein Data Bank that have the same backbone torsions. Valid conformations of the BC loop (or loops EF and BG) may be created by searching the Brookhaven Protein Data Bank for 1 0 loops that have similar anchoring geometries or by imposing random backbone conformations within the selected loops and filtering the results to fit the anchor residues. Both of these knowledge-based methods generate initial structures which can be subjected to force-field minimizations to produce feasible geometries.

S

1 5 In addition to the flexibility inherent to the peptide binding site. the interface between the two SH2 domains provides opportunities for exploring additional conformational states. The interface that is exclusive to the two SH2 domains provides a total buried surface area of only about 200 A2, and consists largely of hydrogen bonding contacts, many of which are mediated by water. Experiments with isoelectric focusing gels suggest that uncomplexed ZAP-NC exhibits 2 0 conformational mobility between the two SH2 domains that is subdued upon binding to the (1 peptide. Since ZAP function requires that both SH2 domains associate simultaneously with a doubly-phosphorylated ITAM of the TCR, gross displacements between the two SH2 domains may play a regulatory role. Thus, conformations in which the SH2 domains are separated may o represent an inactivated state, and inhibitors that stabilize this orientation become attractive.

2 5 Molecular dynamics simulations of a fully solvated ZAP-NC may provide insight into the 6 structural manifestation of a possible dissociation between the SH2 domains, and an additional target conformation of the uncomplexed protein.

Receptor site mapping encompasses a variety of computational procedures that identify 3 0 energetically favorable binding sites on macromolecules. The most straighforward procedures involve "painting" a solvent-accessible surface (or an otherwise generated cast) of the macromolecular target according to empirically determined physical properties, such as electrostatic or lipophilic potential, degree of curvature, and hydrogen-bonding character. Such methods for thus characterizing the surface of a macromolecule are incorporated in programs 3 5 such as Grasp (Columbia University), DelPhi (Biosym Technologies), MOLCAD (Tripos, Inc.), and Hint (Virginia Commonwealth University). Subsequent molecule design involves identification or design of ligands that possess features complimentary to the identified surface characteristics. More advanced algorithms involve the actual calculation of interaction enthalpies between the target and potential ligands or fragments. In practice, the coordinates of 36 the protein or protein fragment of interest (which may be rotated or otherwise transformed) are stripped of any undesired ligand (or portion thereof) and/or of any undesired solvent molecules. The coordinates are then processed to attach molecular mechanics parameters to the atomic positions to provide a processed target for mapping. The target may be partitioned into discrete binding sites. The target or partitioned sites thereof are flooded with given functional group fragments that are subsequently allowed to relax into desired locations, as in the program MCSS (Molecular Simulations, Inc.), or are encased within a regular lattice of site points on which single fragment probes are positioned sequentially; examples of programs that exploit the site-lattice algorithm include Grin/Grid (Molecular Discovery, Ltd.), Ludi (Biosym Technologies), Leapfrog (Tripos, Inc.), and Legend (University of Tokyo). In both techniques, the enthalpic contribution to binding affinity is estimated with a molecular mechanics force- °field, and appropriate positions of selected functional groups are determined systematically.

In the site-lattice approach, a box is defined enclosing a desired portion of the target within a 1 5 defined lattice. The lattice resolution, the distance between lattice points, may be defined by the practitioner or may be set by the computer program. Likewise, other parameters of points within the lattice, such as hydrophobicity or other characteristics, may be similarly defined.

Probes computer models) of one or more selected moieties, functional groups, molecules or molecular fragments are positioned at lattice points and the interaction energy of the probetarget pair is determined for each such lattice point. The data for each selected moiety, functional group, etc. is collected and may be recovered as a data set, visualized on a computer monitor or printed out in various text or graphic formats.

000005 o As an alternative to positioning a moiety at each of a set of lattice points, one may, as previously mentioned, flood the target (defined by the coordinates as described above) with multiple copies of a selected fragment, moiety, molecule, etc. by superimposing the multiple copies into the vicinity of the protein target. The model is then subjected to group minimization molecular mechanics minimization) calculations to identify points or areas of favorable interaction. Data may be handled as in the lattice approach.

One application of this method to the structure of ZAP-NC involves the crystal structure coordinates stripped of both the peptide ligand 1) and experimentally observed water molecules. The binding site so revealed comprises all protein residues that reside within van der Waals distance of any position previously occupied by the peptide. This "conventional" binding site is enlarged to include the bulk of the proximal protein surface, hence additional crevices and depressions not occupied by known ligands for any SH2 domains are considered as potential "auxiliary" binding regions, and their occupation could contribute significantly to the inhibition of ZAP association with the T cell receptor. Similar definition of the binding face of ZAP-NC applies to any alternate coordinates derived experimentally or via the modeling 37 procedures described above. Receptor site mapping, as well as other methods described herein, may be applied to the 3-D structure of a ZAP family member to design or select ligands capable of binding to an SH2 domain or other site within the ZAP-NC (or ZAP family-NC) structure.

Receptor site maps provide the seeds for ligand evolution via Database searches, which are described above, and for Grow/link methods for de Novo design of new chemical entities.

Programs for ligand growth first access extensible fragment dictionaries in order to place appropriate functional groups at site points. A genetic algorithm or a subgraph isomorphism protocol is then invoked to connect the fragments with small aliphatic chains or rings.

1 0 Stochastic enhancements may be introduced by modification of internal degrees of freedom as well as translation and rotation of the candidate model within the binding cavity. The resulting sets of molecules are scored and filtered by functions that consider the steric constraints of the binding site, the complimentarity of electrostatic and hydrophobic interactions, and a solvation estimate. Programs of this type that could be applied for the design of new ligands for ZAP-NC 1 5 include Ludi (Biosym Technologies), Leapfrog (Tripos, Inc.), Legend (University of Tokyo), Grow (Upjohn), Builder/Delegate (University of California, San Francisco), and Sprout (University of Leeds). Clique detection methods provide an alternative strategy to site mapping and ligand growth. DOCK (University of California, San Francisco) and similar programs fill a given binding site with the smallest set of atom-sized spheres possible; a database search then attempts to orient ligands such that the atoms superimpose onto the centers (or "nuclei") of the site-filling spheres. The shape complimentarity is augmented by scoring functions that include oo the steric requirements of the cavity and a potential energy function.

Optimization of ligands (from any source) may be enhanced using the three dimensional S 2 5 structural of ZAP-NC. Use of receptor site maps or hydropathic profiles of ZAP-NC may be used to identify preferred positions for functional group components of ligands. and can be used to filter or constrain conformational searches of iigand structures which would otherwise typically be controlled by minimal steric considerations of the ligand structures themselves.

The availability of an explicit binding site also permits one to determine the mode of ligand binding to the target protein via methods that utilize force-fields directly in simulated annealing, distance geometry, Metropolis Monte Carlo, or stochastic searches for binding modes.

Examples of programs that can be applied to rationalize ligand binding to ZAP-NC include Autodock (Scripps Clinic), DGEOM (QCPE #590), Sculpt (Interactive Simulations, Inc.), or any of the molecular dynamics programs described above. Once a tractable set of possible binding orientations is obtained, one can readily identify the appropriate mode of binding through modifications in test ligands designed to alter in a predictable fashion the binding affinity of each model under consideration. For instance, a ligand may be modified to contain a functional group at a position which is inconsistent with one binding model, yet consistent with another model. Binding data can then be used to weed out "disproven" models. Once iterative 38 weeding of unlikely binding modes generates an appropriate model, possibilities for improvement of the lead become readily apparent from the local protein environment.

An alternative protocol for ligand optimization involves 3D database searching in conjunction with knowledge of the binding site. Modeling can reveal multiple candidates for the bioactive conformation of a given ligand. A probe for the correct conformation can include a 3D search to identify several constrained mimics of each possible conformer. Structure-activity relationships of the unconstrained ligand would suggest which functional groups should be retained in the constrained mimics. Finally, the steric and electrostatic requirements of the 1 0 binding site could constitute a filter for prioritizing the resultant possibilities.

The structure of ZAP-NC permits accurate model-building of homologous proteins, and their subsequent use in drug design. The SH2 domains and inter-domain coiled coil regions of the protein tyrosine kinase p 72 SYk share a high degree of sequence similarity with ZAP-70. The 15 ZAP-NC structure may be readily used in the development of a reliable model of Syk-NC by either knowlege-based template building methods, or by iterations of directed point mutations followed by local molecular mechanics minimizations. Examples of programs that can be applied in the development of a model of Syk-NC include Composer (Birbeck College), Modeler (MSI), and Homology (Biosym Technologies). The resultant model can then be subjected to any of the 20 CADD techniques described above.

F. Characterization of Compounds Compounds designed, selected and/or optimized by methods described above may be evaluated for 2 5 binding activity with respect to proteins containing one or more SH2 domains of interest using various approaches, a number of which are well known in the art. For instance, compounds may be evaluated for activity as competitive inhibitors of the binding of an SH2 domain with a phosphorylated ligand thereto. See e.g. Pawson, US Patent No. 5,352,660 (4 October 1994).

Surface plasmon resonance (SPR) technology may be used for evaluating the binding properties of compounds with respect to one or more SH2 domains of interest (see Panayotou et al, 1993, Molecular and Cellular Biology 13: 3567-3576), as can fluorescence proximity methods, and other methods known in the art.

SPR methodologies measure the interaction between two or more macromolecules in real-time through the generation of a quantum-mechanical surface plasmon. The SPR methodology as exploited by the BIAcore Biosensor (Pharmacia Biosensor, Piscatawy, NJ) focuses a beam of polychromatic light at the interface between a gold film (provided as a disposable biosensor "chip") and a buffer compartment that can be regulated by the user. Attached to the gold film is a 100 nm thick "hydrogel" composed of carboxylated dextran which provides a matrix for the 39 covalent immobilization of analytes of interest. When the focused light interacts with the free electron cloud of the gold film, plasmon resonance is enhanced. The resulting reflected light is spectrally depleted in wavelengths that optimally evolved the resonance. By separating the reflected polychromatic light into its component wavelengths (by means of a prism), and determining the frequencies which are depleted, the BIAcore establishes an optical interface which accurately reports the behavior of the generated surface plasmon resonance. When designed as above, the plasmon resonance-and thus the depletion spectrum-is exquisitely sensitive to mass in the evanescent field (which corresponds roughly to the thickness of the hydrogel). If one component of an interacting pair is immobilized to the hydrogel, and the 1 0 interacting partner is provided through the buffer compartment, the interaction between the two components can be measured in real time based on the accumulation of mass in the evanescent field and its corresponding effects of the plasmon resonance as measured by the depletion spectrum. This system permits rapid and exremely sensitive real-time measurement of the molecular interactions without the need to label either component.

Fluorescence polarization (FP) is a measurement technique that can readily be applied to protein-protein and protein-ligand interactions in order to derive IC50s and Kds of the association reaction between two molecules. In this technique one of the molecules of interest must be conjugated with a fluorophore: this is generally the smaller molecule in the system (in the case of a SH2 system, a phospho-tyrosine-containing peptide). The sample mixture, containing both the ligand-probe conjugate and the protein receptor, is excited with vertically polarized light. Light is absorbed by the probe fluorophores, and re-emitted a short time later.

The degree of polarization of the emitted light is measured. Polarization of the emitted light is dependent on several factors, but most importantly on viscosity of the solution and on the 2 5 apparent molecular weight of the fluorophore.

With proper controls, changes in the degree of polarization of the emitted light depends only on changes in the apparent molecular weight of the fluorophore, which in-turn depends on whether the probe-ligand conjugate is free in solution, or is bound to a protein receptor. Binding assays 3 0 based on FP have a number of important advantages. Key among these are the measurement of and Kds under true homogenous equilibrium conditions, speed of analysis and amenity to automation, and ability to screen in cloudy suspensions and colored solutions.

Automation of such an FP-based assay is achieved using a 96-well fluorescence polarization plate reader. This reader can read polarization values at a sensitivity level of 1nM for fluorescein-labeled molecules, and can read an individual plate in 3 minutes.

40 Fluorescence polarization equilibrium binding assays have been adapted for ZAP, Syk, and Src domains. A binding curve of a doubly-phosphorylated -1 sequence to N,C-ZAP, with associated Scatchard plot of the data is shown in FIG. It will often be preferred that a compound preferentially inhibits the interaction of a particular SH2-containing protein with its natural ligand (or a portion thereof or analog based thereon), e.g. at least an order of magnitude, and even more preferably, at least two orders of magnitude better (by any measure) than it inhibits some other SH2-ligand interaction.

1 0 Such compounds may be further evaluated for activity in inhibiting cellular or other biological events mediated by a pathway involving the interaction of interest using a suitable cell-based assay or an animal model. Cell-based assays and animal models suitable for evaluating inhibitory actvity of a compound with respect to a wide variety of cellular and other biological events are known in the art. New assays and models are regularly developed and reported in the 1 5 scientific literature.

For example, compounds which bind to ZAP-70 may be evaluated for biological activity in inhibiting T cell activation using any conventional assay methods and materials. Thus, compounds which bind to ZAP may be assayed for inhibition of CD4+ and CD8+ T-lymphocytes 20 in vitro and for lack of in vitro toxicity on cytotoxic T-cells within the dose range used to demonstrate in vitro activity. A battery of in vivo models may be used to profile the breadth of the compound's immunosuppressive activity and compare the profile to those of positive controls such as cyclosporin and FK506. Comparisons may also be made to other currently accepted immunosuppressive compounds, i.e. rapamycin, cyclophosphamide, and leflunomide.

2 5 Initial in vivo screening models include: Delayed type hypersensitivity testing, Allogeneic skin transplantation, and Popliteal lymph node hyperplasia. Compounds demonstrating optimal profiles in the above models are advanced into more sophisticated models designed to confirm immunosuppressive activity in specific therapeutic areas including: Rheumatoid arthritis, Transplantation, Graft vs. host disease, and Asthma.

Compounds which bind to SYK may be evaluated for inhibitory activity in a mast cell or basophil degranulation assay. The inhibitory activity of a compound of this invention with respect to cellular release of specific mediators such as histamine, leukotrienes, hormonal mediators and/or cytokines as well as its biological activity with respect to the levels of 3 5 phosphatidylinositol hydrolysis or tyrosine phosphorylation can be characterized with conventional in vitro assays as an indication of biological activity. (See e.g."lgE-induced histamine release from rat basophilic leukemia cell lines: isolation of releasing and nonreleasing clones". Edward L. Barsumian, Chaviva Isersky, Marianne G. Petrino and Reuben P. Siraganian. Eur. J. Immunol. 1981. 11:317-323; Forrest, MJ, 1991, Biochemical 41 Pharmacology 42:1221-1228 (measuring N-acetyl-P glucosaminadase from activated netrophils); and Stephan, et a, J. Biol. Chem. 267:5434-5441 (1992)). For example, histamine release can be measured by a radioimmunoassay using a kit available from AMAC Inc.

(Westbrook, ME). One can thus evaluate the biological activity of compounds which bind to SYK and compare them to one another and to known active compounds such as leflunomide (and its active metabolite, A771726), vanadate, staurosporine, genistein, or other compounds, including clinically relevant compounds, which can be used as positive controls.

Generally speaking, in such assays IC 5 0 scores of 150-300 gM are considered of interest, 1 0 scores of 50-150 lM are considered good, and scores below about 50 uM are of high interest.

Compounds which bind to SYK may also be tested in an ex vivo assay for their ability to block antigen-stimulated contraction of sensitized guinea pig tracheal strip tissue. Activity in this 1 assay has been shown to be useful in predicting the efficacy of potential anti-asthma drugs.

1 5 Numerous animal models of asthma have been developed and can be used (for reviews, see Larson, "Experimental Models of Reversible Airway Obstruction", in THE LUNG, Scientific Foundations, Crystal, West et a Raven Press, New York, pp. 953-965 (1991); Warner etaL, 1990, Am. Rev. Respir. Dis. 141:253-257). Species used in animal models of asthma include mice, rats, guinea pigs, rabbits, dogs, sheep and primates. Other in vivo models 20 available are described in Cross t al., Lab Invest. 63:162-170 (1990)); and Koh, e al, Science, 256:1210-1213 (1992)).

By way of further illustration, compounds which bind to an SH2-bearing protein involved in the transduction of a signal involved in the initiation, maintenance or spread of cancerous 2 5 growth may be evaluated in relevant conventional in vitro and in vivo assays. See Ishii et al., J. Antibiot. XLII:1877-1878 (1989) (in vitro evaluation of cytotoxic/antitumor activity); Sun et al, US Patent 5,206,249 (issued 27 April 1993)(in vitro evaluation of growth inhibitory activity on cultured leukemia cells); and Sun et al, supra (xenograft models using various human tumor cell lines xenografted into mice, as well as various transgenic animal models).

Single and multiple 5 to 7 days) dose investigative toxicology studies are typically performed in the efficacy test species using the intended route of administration for the efficacy study. These investigative toxicology studies are performed to identify maximum tolerated dose, subjective bioavailability from the intraperitoneal or oral routes of administration and estimation of an initial safety margin. Initial bioavailability and pharmacokinetics (blood clearance) of the compounds may be determined, with standard cold or radioactive assay methods, to assist in defining appropriate dosing regimens for the compounds in the animal models.

42 Illustration of drug design To illustrate one approach to using the structure of a ZAP family member in drug design, we used the structural coordinates of the ZAP-NC: 1 complex (see e.g. Appendix I) to characterize amino acid residues of interest with respect to their capability for interaction with ligand molecules. For instance, using the program Sybyl we identified amino acid residues from the Nterminal SH2 domain and C-terminal SH2 domains which are within 10 angstroms of the (-1 peptide ligand and which reside on the protein surface. Residues from that region which are capable of entering hydrophobic interactions with moieties on ligand molecules are listed in 1 0 Table A. Acidic residues from that region which are capable of entering hydrogen-bonding interactions or ionic (salt-bridge) interactions with moieties on ligand molecules are listed in Table B. Basic residues from that region which are capable of entering hydrogen-bonding interactions or ionic (salt-bridge) interactions with moieties on ligand molecules are listed in Table C. Neutral residues from that region which are capable of entering hydrogen-bonding 1 5 interactions with moieties on ligand molecules are listed in Table D. Residues from that region having appropriately disposed backbone amide carbonyls which are capable of entering hydrogen-bond accepting interactions with moieties on ligand molecules are listed in Table E.

Residues from that region having appropriately disposed backbone amide nitrogens which are capable of entering hydrogen-bond donating interactions with moieties on ligand molecules are 20 listed in Table F.

Table A Table B Table C Table D Table E Table F ALA18 GLU19 ARG17 SER14 PHE56 ARG17 LEU40 GLU21 ARG37 SER16 HIS58 VAL47 GLU62 ARG41 GLN38 ALA72 HIS58 LEU48 ASP90 HIS52 CYS39 GLY73 CYS96 ASP92 ARG55 SER42 ASP92 ARG170 PHE56 GLU171 HIS57 TYR87 GLY93 LYS193 PHE59 GLU172 HIS58 THR169 LEU168 GLU194 GLU174 LYS75 TYR178 PRO191 HIS210 ILE61 GLU194 ARG170 SER201 TYR198 LEU212 ILE71 GLU225 ARG190 TYR204 VAL208 GLU225 ALA72 GLU237 ARG192 THR207 HIS210 LYS228 PHE86 ASP244 LYS193 TYR209 PR0224 LEU241 TYR87 HIS210 TYR211 GLU225 ALA243 PRO91 LYS228 SER214 GLY226 GLY245 LEU94 LYS242 CYS222 LYS228 ILE247 LYS251 THR227 ASP244 CYS249 TYR178 TYR238 GLY245 LYS193 CYS249 LEU246 ALA199 LEU200 TYR204 VAL208 TYR209 TYR211 LEU212 LEU223 PR0224 43 LYS228 PHE229 LEU235 TYR238 LEU239 LEU241 LYS242 ALA243 LEU246 ILE247 TYR248 LEU250 Similarly, we have identified amino acid residues from the C-terminal domain and the Nterminal domain which reside at the interface between these two domains which would be capable of interacting with ligand molecules in such a manner as to disrupt the juxtapositioning 5 of domains necessary for binding ZAP-70 to the phosphorylated T-cell receptor. Residues from that region which are capable of entering hydrophobic interactions with moieties on ligand Smolecules are listed in Table G. Acidic residues from that region which are capable of entering hydrogen-bonding interactions or ionic (salt-bridge) interactions with moieties on ligand molecules are listed in Table H. Basic residues from that region which are capable of entering 1 0 hydrogen-bonding interactions or ionic (salt-bridge) interactions with moieties on ligand molecules are listed in Table I. Neutral residues from that region which are capable of entering hydrogen-bonding interactions with moieties on ligand molecules are listed in Table J.

o o Table G Table H Table I Table J GLU62 LYS220 SER14 LEU40 ASP230 LYS242 LEU43 GLU237 GLN38 MET161 GLU244 SER42 LYS220 THR231 PHE229 GLN234 TRP233 TYR238 TYR238 LEU241 LYS242 1 5 Similarly, we have identified amino acid residues from the interdomain (also called spacer A) region which reside at the interface between the two a-helical coils of this region and which would be capable of interacting with ligand molecules in such a manner as to disrupt the observed folding of the NC-ZAP domain. Residues from that region which are capable of entering hydrophobic interactions with moieties on ligand molecules are listed in Table K.

2 0 Acidic residues from that region which are capable of entering hydrogen-bonding interactions or ionic (salt-bridge) interactions with moieties on ligand molecules are listed in Table L.

Basic residues from that region which are capable of entering hydrogen-bonding interactions or ionic (salt-bridge) interactions with moieties on ligand molecules are listed in Table M.

44 Neutral residues from that region which are capable of entering hydrogen-bonding interactions with moieties on ligand molecules are listed in Table N.

Table K Table L Table M Table N ILE142 GLU134 ARG119 GLN145 ILE153 GLU150 ARG124 THR156 LEU133 ARG160 TYR126 LEU138 LEU152 MET122 PHE115 TRP131 TYR126 VAL114 VAL123 VAL127 VAL149 5 The amino acid residues listed in Tables A-N can be used to define binding sites on the protein for moieties on ligand molecules. A binding site comprises any subset of the foregoing residues which are within about 10 angstroms of one another. For example, the residues S. CYS39, ARG41, SER42, PRO60, GLU62, LYS220, and ASP230 comprise such a binding site.

1 0 We contemplate a new class of ligands for ZAP family members based on the foregoing type of evaluation. Specifically, this class comprises compounds containing one or more moieties which S. are each capable of interacting with one or more of the foregoing residues, preferably with one or more binding sites defined by the foregoing residues. A subset of such compounds are those which contain at least two moieties, of which at least one is a substituted or unsubstituted 1 5 phosphate or phosphate mimic a substituted or unsubstituted phosphonate moiety). In embodiments in which those moieties are substituted, the substituent may be alkyl, aryl, or arylalkyl.

The term alkyl is intended to include both saturated and unsaturated straight chain, branched, 2 0 cyclic, or polycyclic aliphatic hydrocarbons which may contain oxygen, sulfur, or nitrogen in place of one or more carbon atoms, and which are optionally substituted with one or more functional groups selected from the group consisting of hydroxy, C 1

-C

8 alkoxy, acyloxy, carbamoyl, amino, N-acylamino, ketone, halogen, cyano, carboxyl, and aryl. Alkyl groups are preferably lower alkyl, i.e. containing 1 to 8 carbon atoms.

The term aryl is intended to include stable cyclic, heterocyclic, polycyclic, and polyheterocyclic unsaturated C3-C14 moieties, exemplified but not limited to phenyl, biphenyl, naphthyl, pyridyl, furyl, thiophenyl, imidazoyl, pyrimidinyl, and oxazoyl; which may further be substituted with one to five members selected from the group consisting of hydroxy, C 1

-C

8 alkoxy, C 1

-C

8 branched or straight-chain alkyl, acyloxy, carbamoyl, amino, 45 N-acylamino, nitro, halogen, trifluoromethyl, cyano, and carboxyl (see e.g. Katritzky, Handbook of Heterocyclic Chemistry).

The ligands may contain one or more amide bonds, but are preferably non-peptidic. Preferably the molecular weight of the ligands is under 1200, more preferably under 750, more preferably under 500. Peptides and peptidic molecules comprise two or more naturally occurring a-amino acids linked by peptide bonds (primary amide bonds, except where the amino acid is proline).

1 0 The ability of a ligand or a moiety on a ligand to interact with a particular residue or set of residues in a binding site may be determined by noting the proximity of a ligand moiety to a residue of interest. Proximity may be determined by physical methods such as x-ray S. crystallography or NMR evaluation of a co-complex of the protein and ligand, or may be determined through modeling studies in which the structure of the ligand is docked with the S. 15 structure of the protein using programs such as described above. A number of commercially available programs are capable of conveniently evaluating a modeled or experimentally determined structure and identifying atoms involved in hydrogen-bonding or hydrophobic interactions. Generally, hydrogen bonding (which includes salt bridge and other ionic interactions) occurs across distances of about 2.8 3.5 angstroms, more usually up to about 3.2 angstroms, and through donor-H-acceptor angles of about 1800 600. Hydrophobic interactions occur accross distances of up to about 5 angstroms, more preferably up to about angstroms and more frequently up to about 4 angstroms, depending on the nature of the atoms involved. Again, any of a number of commercially available computer programs may be used to identify hydrogen bonding and hydrophobic interactions between ligand moieties and protein atoms.

G. Pharmaceutical Compositions and Uses of Inhibitors of ZAP family members 3 0 Compounds which bind to one or more ZAP family members may be used as biological reagents in binding assays as described herein for functional classification of an SH2-bearing protein, particularly a newly discovered protein, based on ligand specificity.

Moreover, compounds identified as described above can be used to inhibit the occurrence of 3 5 biological events resulting from molecular interactions mediated by a ZAP family protein containing one or more SH2 domains. This invention thus provides a method and materials for inhibiting (totally or partially) the interaction between such a protein and a natural ligand thereto a naturally occurring protein (typically), or a portion or analog thereof, which binds in a cell to the ZAP family protein) or a biological activity mediated by such interaction.

46 In this method, a compound identified or obtained as described herein is combined or contacted with the ZAP family protein, such as by introducing the compound into a cell in which the molecular interaction is to be inhibited. Following introduction of the compound, the interaction of the ZAP family protein and its natural ligand is inhibited as may be readily detected.

Inhibiting such interactions can be useful in research aimed at better understanding the biology of SH2-mediated events.

In general, inhibitors of SH2-mediated interactions would be useful, for example, in the diagnosis, prevention or treatment of conditions or diseases resulting from a cellular processes 1 0 mediated by the interaction of SH2 bearing protein with a natural ligand therefor. For example, a patient can be treated to prevent the occurence or progression of osteoporosis or to reverse its course by administering to the patient in need thereof an SH2 binding or blocking agent which selectively binds Src SH2. There are many other conditions for which SH2 binding or blocking agents may be useful therapeutically, including breast cancer where the SH2 domain-containing 1 5 proteins Src, PLCg and Grb7 have been implicated. Other relevant conditions include prostate cancer, in which case targeting Grb2, PLCg, and P13K, all of which contain SH2 domains, may be useful in treatment or prevention of the disease. Inhibition of the interaction of Grb2 or Abl SH2 domains with Bcr-abl may be useful to treat chronic mylogenous leukemia (CML) or acute myelogenous leukemia (AML). Still other relevant applications of an SH2 inhibitor would be to 20 prevent interferon-, growth factor-, or cytokine-mediated diseases inflammatory diseases) by targeting the SH2 domains of STAT proteins.

i. Of particular interest are agents that block the interaction of ZAP family members with their natural ligands. For instance, inhibitors of interactions involving ZAP-70, which is believed to be involved in activation of T-cells, would be useful as an immunosuppressant in the treatment and prevention of autoimmune diseases and to prevent rejection of skin and organ transplants.

Inhibitors of interactions of SYK with natural ligands would be useful in the treatment and prevention of asthma and untoward allergic reactions.

An inhibitor selected or identified in accordance with this invention can be formulated into a pharmaceutical composition containing a pharmaceutically acceptable carrier and/or other excipient(s) using conventional materials and means. Such a composition can be administered to an animal, either human or non-human, for therapy of a disease or condition resulting from cellular events involving a molecular interaction mediated by a ZAP family protein.

3 5 Administration of such composition may be by any conventional route (parenteral, oral, inhalation, and the like) using appropriate formulations as are well known in this art. The inhibitor of this invention can be employed in admixture with conventional excipients, ie, pharmaceutically acceptable organic or inorganic carrier substances suitable for parenteral administration.

47 Pharmaceutical applications By virtue of its capacity to inhibit protein-protein interactions required for cellular events of pharmacologic importance, a compound identified as described herein may be used in pharmaceutical compositions and methods for treatment or prevention of various diseases and disorders in a mammal in need thereof.

Mammals include rodents such as mice, rats and guinea pigs as well as dogs, cats, horses, cattle, sheep, non-human primates and humans.

The preferred method of such treatment or prevention is by administering to a mammal an effective amount of the compound to prevent, alleviate or cure said disease or disorder. Such oo effective amounts can be readily determined by evaluating the compounds of this invention in conventional assays well-known in the art, including assays described herein.

1 Therapeutic/Prophylactic Administration Pharmaceutical Compositions The invention provides methods of treating, preventing and/or alleviating the symptoms and/or severity of a disease or disorder referred to above by administration to a subject of a in an amount effective therefor. The subject will be an animal, including but not limited to animals such as cows, pigs, chickens, etc., and is preferably a mammal, and most preferably human.

Various delivery systems are known and can be used to administer the inhibitor, e.g., encapsulation in liposomes, microparticles, microcapsules, etc. One mode of delivery of •interest is via pulmonary administration, as detailed more fully infra. Other methods of 25 introduction include but are not limited to intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural and oral routes. The inhibitor may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings oral mucosa, rectal and intestinal mucosa, etc.) and may be administered together with other biologically active agents.

3 0 Administration can be systemic or local. For treatment or prophylaxis of nasal, bronchial or pulmonary conditions, preferred routes of administration are oral, nasal or via a bronchial aerosol or nebulizer.

In specific embodiments, it may thus be desirable to administer the inhibitor locally to the area in need of treatment: this may be achieved by, for example, and not by way of limitation, local infusion during surgery, topical application, by injection, by means of a catheter, by means of a suppository, or by means of a skin patch or implant, said implant being of a porous, nonporous, or gelatinous material, including membranes, such as sialastic membranes, or fibers.

48 This invention also provides pharmaceutical compositions. Such compositions comprise a therapeutically (or prophylactically) effective amount of the inhibitor, and a pharmaceutically acceptable carrier or excipient. Such a carrier includes but is not limited to saline, buffered saline, dextrose, water, glycerol, ethanol, and combinations thereof. The carrier and composition can be sterile. The formulation should suit the mode of administration.

The composition, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. The composition can be a liquid solution, suspension, emulsion, tablet, pill, capsule, sustained release formulation, or powder. The composition can be formulated as a suppository, with traditional binders and carriers such as triglycerides. Oral formulation can include standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate, etc.

In a specific embodiment, the composition is formulated in accordance with routine procedures 1 5 as a pharmaceutical composition adapted for intravenous administration to human beings.

Typically, compositions for intravenous administration are solutions in sterile isotonic aqueous buffer. Where necessary, the composition may also include a solubilizing agent and a local anesthetic to ease pain at the side of the injection. Generally, the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachette indicating the quantity of active agent. Where the composition is to be administered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade water or saline.

Where the composition is administered by injection, an ampoule of sterile water for injection or saline can be provided so that the ingredients may be mixed prior to administration.

S Administration to an individual of an effective amount of the inhibitor can also be accomplished topically by administering the compound(s) directly to the affected area of the skin of the individual. For this purpose, the inhibitor is administered or applied in a composition including a pharmacologically acceptable topical carrier, such as a gel, an ointment, a lotion, or a cream, which includes, without limitation, such carriers as water, glycerol, alcohol, propylene glycol, fatty alcohols, triglycerides, fatty acid esters, or mineral oils.

Other topical carriers include liquid petroleum, isopropyl palmitate, polyethylene glycol, ethanol polyoxyethylene monolaurate in water, or sodium lauryl sulfate in water. Other materials such as anti-oxidants, humrnectants, viscosity stabilizers, and similar agents may be added as necessary.

49 In addition, in certain instances, it is expected that the inhibitor may be disposed within devices placed upon, in, or under the skin. Such devices include patches, implants, and injections which release the compound into the skin, by either passive or active release mechanisms.

Materials and methods for producing the various formulations are well known in the art [see e.g. US Patent Nos. 5,182,293 and 4,837,311 (tablets, capsules and other oral formulations as well as intravenous formulations)].

The effective dose of the inhibitor will typically be in the range of about 0.01 to about mg/kgs, preferably about 0.1 to about 10 mg/kg of mammalian body weight, administered in single or multiple doses. Generally, the inhibitor may be administered to patients in need of such treatment in a daily dose range of about 1 to about 2000 mg per patient.

The amount of the inhibitor which will be effective in the treatment or prevention of a 1 5 particular disorder or condition will depend on the nature of the disorder or condition, and can be determined by standard clinical techniques. In addition, in vitro or in vivo assays may optionally be employed to help identify optimal dosage ranges. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems.

The precise dosage level of the inhibitor, as the active component(s), should be determined as in the case of all pharmaceutical treatments, by the attending physician or other health care provider and will depend upon well known factors, including route of administration, and the age, body weight, sex and general health of the individual; the nature, severity and clinical stage of the disease; and the use (or not) of concomitant therapies.

°oeoo The invention also provides a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of the pharmaceutical compositions of the invention.

Optionally associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceutical or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration.

Pulmonary Administration In one embodiment of this invention, the inhibitor is administered by pulmonary administration, e.g. via aerosolization. This route of administration may be particularly useful for treatment or prophylaxis of bronchial or pulmonary infection or tumors.

Pulmonary administration can be accomplished, for example, using any of various delivery devices known in the art (see Newman, 1984, in Aerosols and the Lung Clarke and Davia Butterworths, London, England, pp. 197-224; PCT Publication No. WO 50 92/16192 dated October 1, 1992; PCT Publication No. WO 91/08760 dated June 27, 1991; NTIS Patent Application 7-504-047 filed April 3, 1990 by Roosdorp and Crystal), including but not limited to nebulizers, metered dose inhalers, and powder inhalers. Various delivery devices are commercially available and can be employed, Ultravent nebulizer (Mallinckrodt, Inc., St. Louis, Missouri); Acorn II nebulizer (Marquest Medical Products, Englewood, Colorado), Ventolin metered dose inhaler (Glaxo Inc., Research Triangle Park, North Carolina); Spinhaler powder inhaler (Fisons Corp., Bedford, Massachusetts) or Turbohaler (Astra). Such devices typically entail the use of formulations suitable for dispensing from such a device, in which a propellant material may be present.

Ultrasonic nebulizers tend to be more efficient than jet nebulizers in producing an aerosol of respirable size from a liquid (Smith and Spino, "Pharmacokinetics of Drugs in Cystic Fibrosis," Consensus Conference, Clinical Outcomes for Evaluation of New CF Therapies, Rockville, Maryland, December 10-11, 1992, Cystic Fibrosis Foundation).

1 A nebulizer may be used to produce aerosol particles, or any of various physiologically acceptable inert gases may be used as an aerosolizing agent. Other components such as physiologically acceptable surfactants glycerides), excipients lactose), carriers, and diluents may also be included.

This invention is not to be limited in scope by the specific embodiments described herein.

Indeed, various modifications of the invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are 4 4 intended to fall within the the scope of the appended claims.

Various patents, patent applications and publications are cited herein, the disclosures of which are incorporated by reference in their entireties.

Experimental Examples I. Protein Preparation A. ZAP-NC: Expression, Purification and Complex Formation Cloning The ZAP-NC was expressed as a glutathione-S-transferase (GST) fusion protein. The DNA sequence encoding residues 1-259 from human ZAP 70 Chan, M. Iwashima, C.W.Turck, A.

Weiss Cel171 649-662 (1992)) was cloned into the pGex expression vector Smith, K.S. Johnson Gene 67, 31-40 (1988))and transformed into E. coli BL21 or E. Coli B834. The 51 resulting construct coded for a thrombin cleavage site and two extra residues (G and S) at the N-terminus of the ZAP-NC.

Expression In a typical preparation the ZAP-NC was produced by the growth and induction of two liters of culture (BL21) in BHI medium. The culture was grown at 25°C to an OD 595nm of 0.8 and induced with 1mM IPTG for 5 hours.

The selenomethionyl (SeMet) ZAP-NC was produced using the auxotrophic strain of E. coli 834 Leahy, H.P. Erickson, I. Aukhil, P. Joshi, W. Hendrickson Proteins 19 48-54 (1994)) with the selenomethionine replacing the methionine in a defined media. The SeMet ZAP-NC was grown in 10 liters of defined media (J.O.Boles, W.H. Tolleson, J.C. Schmidt, R.B. Dunlap, J.D.

Odom, J. Biol. Chem. 267, 22217-22223 (1992)) supplemented with 0.5% thiamine using 50mg/L of D,L selenomethionine. The culture was grown at 30°C to an OD 595nm of 0.8 and 1 5 induced for 10-15 hours.

Purification The GST fusion proteins were isolated using glutathione agarose and then cleaved with thrombin.

ZAP-NC was separated from the GST by binding the tandem SH2 domain to a phosphotyrosine 20 agarose column and eluting with a salt gradient. Subsequently the ZAP-NC was further purified by hydrophobic interaction chromatography on a phenyl sepharose column. The protein was stored under argon with 500mM NaCI and 10mM dithiothreitol at 4°C. A typical purification is listed below. Both the ZAP-NC and the SeMet ZAP-NC were judged to be >95% pure by Nterminal analysis and SDS gel electrophoresis. Mass spectrometric analysis of the ZAP-NC and 2 5 SeMet ZAP-NC indicated >95% incorporation of the selenomethione.

Complex preparation Complexes of the ZAP-NC plus the C 1 peptide (NQLpYNELNLGRREEpYDVLD) were prepared by adding a 2-fold excess of peptide to the protein and then running the sample on a gel filtration 3 0 column. The peptide was dissolved in 200ul of 100mM Tris, pH 8.0. and added to 6mg of protein. The sample was incubated at room temperature for -30min, then filtered through a 0.2 micron filter. A Superdex 75 16/60 column was equilibrated in 20mM Tris containing 100mM NaCI and 5mM DTT, pH 8.0 and the sample was loaded and 3mL fractions were collected.

The complex eluted at 65.6mL and peak fractions were pooled based on protein A(280).

3 5 Analysis of complexation was done on a homogenous 20% native gel.

52 A typical Zap-NC Purification Cell Lysis: 1) Lysed -20g cells using French pressure cell in 40mL of Buffer A: 2) Diluted 1:1 with Buffer B 3) Centrifuged at -30,000 xg for 30min removed the supernatant.

Glutathione Column 2.6x10: 1) Loaded the supematant onto a glutathione column equilibrated into Buffer B.

1 0 2) Washed with -100mLBuffer B then Buffer C to baseline.

.f 3) Eluted in Buffer D; 5mL fractions were collected and pooled.

Thrombin Cleavage: 1) Added 200mM NaCI to the pool, then added human thrombin at lug/mg protein 1 5 2) Incubated on nutator at room temp. Samples were taken run on an SDS gel while continuing to incubate. Reaction was complete at 40min. (PMSF can be added to stop the reaction.) 3) Diluted the pool x5 when cleavage was complete with 20mM Tris pH 8/5mM DTT.

20 Phosphotyrosine Column: 26x7.5cm: 1) Loaded the pool onto the column equilibrated in Buffer E: 2) Washed& eluted using a 5 CV gradient to buffer F. 5mL fractions were collected.

3) Pooled peak.

Phenyl Sepharose Column 26x17.5cm: 1) Diluted the pool 1:1 with 3M (NH4)2S04 2) Equilibrated the column with Buffer G: 3) Loaded the protein, washed to baseline, then eluted in a 3 CV gradient to Buffer H: Pooled peak fractions.

4) Added 500mM NaCI to peak pool and 5mM DTT. Stored at 4 0 C under argon.

Buffers Used: Glutathione Phosphotyrosine Phenyl Separose Buffer A Buffer E: Buffer G: Triton 20mM Tris pH 7.6 20mM Tris pH 8 400mM NaCI 50mM NaCI 1.5M (NH4)2S04 DTT 5mM DTT 5mM DTT 1mM Pefabloc Buffer F: Buffer H: Buffer B 20mM Tris pH 7.6 20mM Tris pH 8 Triton 2M NaCI 5mM DTT 53 DTT 5mM DTT Buffer C

PBS/

DTT

Buffer D: 100mM Tris pH 8 100mM NaCI reduced glutathione 2mM DTT B. Syk-NC Cloning and Expression 5 The DNA sequence encoding residues 6-265 of human Syk was cloned into the pET expression vector and transformed into E. coli BL21(DE3) (Shiue, et al. Molecular and Cellular Biology 15, 272-281 (1995)) In a typical preparation Syk-NC was produced from the growth and induction of two liters of culture in BHI medium supplemented with 200ug/mL ampicillin. The :*culture was grown at 250C to an OD at 595nm of 1-2, induced with 1mM IPTG, and harvested 4 1 0 hours later.

Purification All operations were performed in a cold room at The cells were lysed using a French pressure cell and 2X volumes of lysis buffer, 20mM Tris pH 8, 500mM NaCI, 5mM DTT, and 1 5 1mM pefabloc. The supernatant was collected by high speed centrifugation, diluted 2-fold with buffer A (20mM Tris pH 8, 5mM DTT) and applied to a 1.6x10 cm polyethylenimine anion exchange column equilibrated with the same buffer. The flow through was dialyzed overnight vs.

buffer B (20mM Tris pH 7.4, 5mM DTT, 50mM NaCI) and then loaded onto a phosphotyrosine agarose column. The Syk-NC protein bound to the column and was eluted with a 2 0 salt gradient, 50mM to 2M NaCI in 4 CV. The Syk-NC protein was collected and dialyzed into buffer C: 50mM Mes pH 6.2, 5mM CaCl2, 5mM DTT. After dialysis the protein sample was centrifuged at high speed and then applied to a Source 15S column 16x10cm) equilibrated in buffer C. The column was then washed with buffer C and eluted using a salt gradient, 0 to 750mM NaCI in 5 CVs. The peak fraction was pooled. SDS gel electrophoresis indicated that the 2 5 protein was >95% pure. N-terminal sequencing and mass spec analysis confirmed the expected sequence. The protein concentration was determined by measuring the absorption at 280nm. The purified protein was stored at 40 with 10mM DTT.

Syk-NC and peptide complexes 3 0 Complexes have been made with a number of different y and r peptides of different lengths. In a typical experiment, a two fold excess of peptide was dissolved in 100mM Tris buffer and added to 10mg of Syk-NC. The sample was incubated at RT for 30 minutes, and then run on a Superdex 54 column (16x60cm) equilibrated in 20mM Tris pH 8, 100mM NaCI, 10mM DTT. Three mL fractions were collected and the peak was pooled.

C. Syk-C Experimental Cloning and expression The C-terminal SH2 domain of human Syk encoding residues 163-265 was cloned into the pGEX2TK expression vector and transformed into E. coli BL21(DE3) (Shiue, et al.

Molecular and Cellular Biology 15, 272-281 (1995); Law, et al. J. Biol. Chem. 269, 12310-12319 (1994)). Isotopically labeled glutathione-S-transferase (GST)-Syk-C was produced from the growth and induction of two liters of culture in M9 medium supplemented with 1g/L of 1 5 NH4CI and/or 3g/L of 1 3 C glucose to obtain uniformly labeled Syk-C SH2. The Sfractionally labeled 13C Syk-C sample was prepared by supplementing the M9 medium with 4.15g/L of a mixture containing a 9:1 ratio of unlabeled glucose: 1 3 C glucose just S 1 5 prior to induction. In a typical preparation the culture was grown at 25 C to an optical density (OD) at 595nm of 1.0, induced with 1mM isopropyl-b-D-thiogalactopyranoside (IPTG), and harvested 5 hours later. Cells were stored at -80°C until use.

Purification The cells were lysed and the protein was affinity purified over glutathione agarose. The GST fusion protein was cleaved with thrombin, and further purified over phosphotyrosine agarose •and ion exchange resin to yield an SH2 domain that was >98% pure by SDS gel electrophoresis.

A typical purification is outlined below. N-terminal sequencing and mass spectroscopic analysis have confirmed the expected sequence. The purified protein was stored under argon with an S 2 5 excess of dithiothreitol (DTT).

Complex Preparation Syk-C SH2 protein: pTyr76 peptide complex samples were prepared by adding a two fold molar excess of the pTyr76 peptide dissolved in 0.5mL NMR buffer (50mM Tris-dil, 0.15N NaCI, 10mM DTT-d8, 0.025% NaN3, pH=7.0) to the Syk-C protein dissolved in the same buffer.

This mixture was incubated overnight at 8°C then concentrated and further equilibrated using CentriconlO microconcentrators at 14°C. Five exchanges of buffer, 2mL to 200mL, ensured complete equilibration. Aliquots of the filtrate and the final complex solution were taken and analyzed by HPLC. All NMR samples contained 2-4mM protein.

55 A typical Syk-C purification Cell Lysis: 1) About 7g frozen pelleted cells were thawed in two volumes of PBS, 0.5% Triton X- 100, 500mM NaCI, 5mM DTT, 2mM EDTA, imM PMSF.

2) The resulting homogenate was lysed using a 20K Manual-Fill FRENCH Pressure Cell at 16,000 psi for two passes.

3) Lysed cells were again diluted with two volumes fresh lysis buffer, stirred for minutes, then centrifuged for 40 minutes at 30,600 x g to sediment cell debris.

4) Supernatant was filtered through 0.8pm Supor membrane filters prior to column loading. All actions carried out at 4 0

C.

Glutathione Aaarose Chromatographv: 1) 26 x 100mm Glutathione Agarose column was equilibrated with PBS, 2mM DTT.

15 2) Filtered bacterial lysate was loaded at 2 ml/minute, then column was washed with PBS, 0.5% Triton X-100, 500mM NaCI, 2mM DTT, followed by PBS, 2mM DTT.

3) GST fusion protein was eluted with 100mM Tris, 100mM NaCI, 20mM Reduced **Glutathione, 2mM DTT, pH Enzymatic Cleavage of GST Fusion Protein: 1) 1 unit of human thrombin was added per mg of total protein in the Glutathione **Agarose eluate.

2) The thrombin was allowed to react for-16 hours at 4°C with slow magnetic stirring.

3) Completion of cleavage was verified by 20% SDS gel, then the reaction was stopped 25 with imM PMSF.

4) Cleaved fusion protein was filtered through 0.2 im Supor membrane prior to loading on Phosphotyrosine Agarose column.

Phosphotyrosine Aaarose Chromatography: 1) 26 x 100mm Phosphotyrosine Agarose column was equilibrated with Buffer A Tris, 100mM NaCI, 5mM DTT, pH 7.4.) 2) Cleaved fusion protein was loaded at 2 ml/minute then washed back to baseline with Buffer A.

3) Syk-C was eluted with a 0-100% B gradient in 4 column volumes. Buffer B A 1.9M additional NaCI.

PEI Chromatography: 1) 16 x 53mm polyethyleneimine column was equilibrated with Phosphotyrosine Buffer A.

56 2) Pooled Phosphotyrosine peak was loaded over PEI at 5 ml/minute then washed with Buffer A. Syk-C was in the flowthrough.

D. ZAP-C Experimental Cloning and exoression The C-terminal SH2 domain of human ZAP 70 was produced as a glutathione-S-transferase (GST) fusion protein. Residues 155-258 of ZAP 70 were cloned into a pGEX expression vector and transformed into E. coli BL21. In a typical fermentation ZAP-C was produced from the 1 0 growth and induction of four liters of culture in LB media supplemented with 200mg/mL ampicillin. The culture was grown at 37 0 C to an OD at 595nm of 1, induced with 1mM IPTG and harvested four hours later. Just prior to induction the temperature was dropped to 25 0 C. 1 5

N-

labeled ZAP-C was produced from the growth and induction of culture in M9 medium supplemented with 1g/L of 1 5 NH4CI. Cells were stored at -80 0

C.

1 Purification The ZAP-C cells were lysed and the protein was affinity purified over glutathione agarose. The GST fusion protein was cleaved with thrombin, and further purified over phosphotyrosine agarose to yield an SH2 domain that was >95% pure by sodium dodecyl sulfate (SDS) gel 2 0 electrophoresis. N-terminal sequencing confirmed the expected sequence. The purified protein was stored under argon with an excess of dithiothreitol (DTT).

9 9 A typical ZAP-C purification Cell Lysis: 1) 50g of frozen ZAP-C cells were thawed in two volumes of PBS, 0.5% Triton, 500mM NaCI, 5mM DTT, 2mM EDTA, 1mM PMSF.

2) The resulting homogenate was lysed using a Minnie Rannie cell disruptor at 16,000 psi for three passes.

3) The cell lysate was centrifuged for 40 minutes at 30,000 x g.

4) The supernatant was collected and filtered through a 0.8mm membrane prior to column loading. All actions were carried out at 4 0

C.

Glutathione Agarose Chromatography: 1) A 26 x 100mm glutathione agarose column was equilibrated with PBS, 2mM DTT.

2) Filtered bacterial lysate was loaded at 2mL/minute, then column was washed with Triton, 500mM NaCI, 2mM DTT followed by PBS, 2mM DTT.

3) GST fusion protein was eluted with 100mM Tris, 100mM NaCI, 2mM DTT reduced glutathione pH 8.

57 Enzymatic Cleavage of GST Fusion Protein: 1) 1 unit of human thrombin was added per mg of protein in the glutathione agarose eluate.

2) The thrombin was allowed to react overnight at 4°C with slow stirring.

3) Additional thrombin (1unit/mg protein) was added to the protein solution in the morning and the cleavage reaction was monitored by SDS gel. Upon completion the reaction was stopped with 1mM PMSF.

1 0 Phosohotvrosine Aaarose Chromatographv 1) A 26 x 80mm phosphotyrosine agarose column was equilibrated with Buffer A (20mM Tris, 100mM NaCI, 2mM DTT, 2mM EDTA, pH 7.4. .o One-half of the cleaved fusion protein was loaded on the column at 2mLminute and then washed to baseline with Buffer A. The ZAP-C was eluted with a 0-100% B gradient 1 5 in 4 column volumes. (Buffer B=A+1.9M NaCI.) 3) The phosphotyrosine chromatography was then applied to the second half of the cleaved fusion protein. The ZAP-C fractions were collected and analyzed by UV/visible spectroscopy.

II. Preparation Of Ligands All peptides were synthesized by automated solid-phase synthesis on Applied Biosystems 431A or 433A synthesizers using N-fluorenylmethoxycarbonyl (Fmoc) amino acids bearing TFAlabile side chain protection. Syntheses were performed on a 0.25. to 0.5 mmol scale on Rink 25 resin (Rink, H. Tetrahedron Lett. 1987, 28, 3787-3790). Amino acids (1.0 mmol) were coupled using HBTU/HOBt/DIEA as activating agents. Coupling reactions are 30-50 min. Assembled peptides are acetylated (Ac20/pyridine in DMA) either prior to phosphorylation (single 5 min reaction) or after phosphorylation (2 x 10 min reaction).

Phosphorylation 3 9 4 0 Resin-bound peptide (0.25 mmol) and tetrazole (25-40 equiv/OH) are combined and dried under vacuum in the presence of NaOH pellets in a desiccator overnight. The flask is then flushed with N2 and DMA (6 mL) added. (tBuO) 2 PNEt2 (10 equiv/OH) is added and the mixture sonicated for 60-90 min. The resin is filtered, washed with DMA (3 x 5 mL) and CH2CI2 (4 x 5 mL). CH2CI2 (5 mL) and mCPBA (2-5 equiv per OH) are added and the mixture sonicated for a further 20-50 min. The resin is filtered, washed with CH2CI 2 (6 x 5 mL), and dried under suction.

58 Cleavage and Deprotection.

Phosphorylated peptide-resin is treated with either TFA: phenol: water or TFA: water: ethanedithiol: anisole: phenol (95:5:5:5:2) for 90-120 min. The resin is filtered, washed with TFA and the filtrate concentrated by rotary evaporation. Diethyl ether is added to precipitate the crude peptide, which is filtered, washed with Et20 and dried.

Peptides are purified by a combination of gel filtration, preparative HPLC, and gel desalting.

Gel filtration. Crude peptide is dissolve in 0.1M NH4HCO3 (10-20 mL) and applied to a Sephadex G-25 column (2.6 x 100 cm) eluted at ca. 0.5 mL/min. Eluent is monitored at 254 or 278 nm and product-containing fractions are identifed by analytical HPLC, pooled, and 1 0 lyophilised.

Preparative HPLC. Peptides were purified on a reversed phase Kromasil C8 column (10 micron particle size, 100 A pore size, 20 x 250 mm) with UV monitoring at 220 nm. Product was eluted with a gradient of either 60/40 MeCN/H 2 0 TFA) in 0.1% aq. TFA, or 60/40 1 5 MeCN/25mM Et3N phosphate pH7 in 25mM Et3N phosphate. The latter buffer required that the isolated pure peptide be desalted, which was achieved by applying the lyophilised product to a Sephadex G-10 or G-15 column (2.6 x 30 cm) eluted with 0.1M NH4HCO 3 at 1-2 mL/min.

Ligand (9) 2 0 The solid phase synthesis of ligand was performed according to the procedures described above, using Na-Fmoc-(O,O-diethyl-a,-difluorophosphonomethyl)phenylalanine (Fmoc- F2Pmp(OEt)20H) (Burke, Smyth, Otaka, Nomizu, Roller, Wolf, G.; Case Shoelson, S.E. Nonhydrolyzable Phosphotyrosyl Mimetics for the Preparation of Phosphatase-Resistant SH2 Domain Inhibitors. Biochem. 1994, 33, 6490-6494) The peptide 2 5 was cleaved from the resin using TFA:phenol:H20:ethanedithiol:anisole (18:1:1:1:1) to afford the crude bis-O,O-diethyl difluorophosphonate-containing product. Final deprotection was achieved by treatment of the crude product with TMS-l:MeCN for 20 min at RT. The solvent was evaporated and the residue dissolved in 0.2M sodium phosphate (pH 7.0: 50 mL).

The solution was washed with diethyl ether (6 x 15 mL) and lyophilised. The product was 3 0 purified as described above.

III. Crystallization Structure Determination A. ZAP-NC was crystallized in complexes with various ligands (see Table 1) as follows: 1. Zap/ 1: The binary complex of ZAP-NC and the (1 19mer (Ligand 5, Table 1) was concentrated to 30 mg/ml in a buffer containing 20 mM Tris at pH 8.5, 200 mM sodium chloride, and 20 mM dithiothreitol. The complex of ZAP-NC with (1 peptide was further treated with 4 mM trimethyllead acetate. Crystals spontaneously grew within 3 weeks in hanging drops containing 13.5 mg/ml protein complex and 10% polyethyleneglycol 4000, 50 mM sodium 59 citrate at pH 6.2, 100mM ammonium acetate, 0.005% sodium azide and 20 mM dithiothreitol over reservoirs of 20% polyethyleneglycol 4000 and 20 mM dithiothreitol. Large crystals were obtained overnight through microseeding. The crystals are monoclinic (P2 1 a=50.11, b=63.37, c=54.00 A, and p =114.440), with one molecule per assymetric unit. Crystals of ZAP-NC complexed with Ligand 8 (Table 1) were obtained under the same conditions.

2. Zap/R2: Crystals of the binary complex of ZAP-NC and the t2 19mer (Ligand 6, Table 1) were obtained under conditions similar to those used for Zap/1, with the few modifications noted below. Protein was concentrated in 10 mM Tris at pH 8.5, 0.5 M sodium chloride, 20 mM 1 0 DTT. 20 to 26 mg/ml protein was treated with 2mM trimenthyllead accetate for one hour before crystallization set-up The drops contained 20 mM sodium accetate and 0.2 M sodium chloride in addition to the conditions described for Zap/ l complex. The final pH in the drops is 6.4 to 6.5. The crystallization was with Zap/ 1 microseeding. (no spontanoues crystallization was obtained).The crystals are monoclinic (P21, a=50.00, b=63.19, c=54.22 A, and p 1 5 =114.60), with one molecule per assymetric unit, and diffracted x-rays to a resolution of 2.2 3. Zap/ 3: Crystals of the binary complex of ZAP-NC and the £3 19mer (Ligand 7, Table 1) were obtained as described for ZAP-NC/ 2 except for the inclusion of sodium accetate in the 20 drops. Crystallization was obtained following microseeding with Zap/ 1 crystals. The crystals are monoclinic (P21, a=49.85, b=63.38, c=54.01 A, and p =114.430), with one molecule per assymetric unit, and diffracted x-rays to a resolution of 2.6 A.

4. Zap/difluorophosphono-l1: Crystals of the binary complex of ZAP-NC and the 25 difluorophosphono analog of C1 19mer (Ligand 9, Table 1) were obtained as described for ZAP-NC/ 1 following microseeding with Zap/ l crystals. The crystals are monoclinic (P21, a=49.77, b=60.87, c=53.58 A, and P =117.090), with one molecule per assymetric unit, and diffracted x-rays to a resolution of 2.2 A.

5. Zap/IgE yTAM 19mer: Crystals of the binary complex of ZAP-NC and the IgE yTAM 19mer (Ligand 1, Table 1) were obtained as described for ZAP-NC/ 1, but at pH 6.6, following microseeding with Zap/C3 crystals.

6. Zap/lgE yTAM 16mer analog: Crystals of the binary complex of ZAP-NC and the IgE yTAM 16mer analog (Ligand 10, Table 1) were obtained as described for ZAP-NC/C1, but at pH with microseeding of Zap/gama crystals in the present of 2% glycerol.

7. Zap/Ligand 11: ZAP-NC was mixed with 3mM Ligand 11 (Table 1) and treated with trimethyllead acetate. Crystals were obtained from a mixture of 12.5 mg/ml ZAP-NC protein, 60 mM Ligand 11 and 1.5 mM trimethyllead acetate in a solution of 10% PEG 4K, 50 mM Tris at pH 8.23 and 10 mM DTT.

B. SYK-NC was crystallized with and without ligand (see Table as follows: 1. SYK-NC (without ligand) was concentrated in 20 mM Tris at pH 8.0, 0.2 M sodium chloride, mM DTT. Crystals were obtained with 12.5 mg/ml protein in 10% PEG 4k, 0.2 M sodium chloride, 50 mM phosphate buffer, pH 7.3, 30 mM DTT.

2. syk/l1: Crystals of the binary complex of SYK-NC and the 1 19mer (Ligand 6, Table 1) 1 0 were obtained with 11mg/ml syk/ 1 complex in 50 mM Hepes at pH 7.2, 9% PEG4k, 4% 2propanol, 0.25 M sodium chloride, 30 mM DTT.

3. syk/y 19: Crystals of the binary complex of SYK-NC and the IgE y 19mer (Ligand 1, Table 1) 1 5 were obtained with 11mg/ml syk/ 1 complex in 50 mM Tris at pH 7.68 or 50 mM Imidazole at pH 7.36, 11% PEG4k, 3.5% 2-propanol, 0.3 M sodium chloride, 30 mM DTT.

4. syk/y15: Crystals of the binary complex of SYK-NC and the IgE y 15mer (Ligand 2, Table 1) were obtained under several different sets of conditions: a. 18mg/ml complex in 10% PEG 4K, 50mM citrate/phosphate buffer at pH 5.6, 0.1 M ammonium chloride, 0.01% sodium azide, 30mm DTT.

b. 18mg/ml complex in 10% PEG 4K, 50mM sodium citrate buffer at pH 5.6, 0.1 M ammonium acetate. 0.5% methylpentanediol, 0.01% sodium azide, 30mM DTT.

c. 18mg/ml complex in 10% PEG 6K, 50mM phosphate buffer at pH 6.2, 0.2 M sodium chloride, 50 mM ammonium accetate, 0.01% sodium azide, 30mM DTT.

syk/y25: Crystals of the binary complex of SYK-NC and the IgE y 25mer (Ligand 3, Table 1) were obtained under several different sets of conditions: a. 12.5 mg/ml SYK-NC/ligand complex in 16% PEG 2K, 50 mM sodium citrate, glycerol, 20 mM DTT, pH6.46.

b. 12.5 mg/ml SYK-NC/ligand complex in 10% PEG 4K, 50 mM sodium citrate, 0.1 M 3 5 ammonium accetate, 20 mM DTT, pH6.3.

6. syk/yTam 27mer: Crystals of SYK-NC with the IgE y 27mer (Ligand 4, Table 1) were obtained as described immediately above in the case of the IgE y 25mer (Ligand 3, Table 1).

61 C. ZAP-NC: 1 three dimensional structure X-ray diffraction data obtained using crystals of the ZAP-NC:-1 complex (one complex per unit cell) were analyzed as described elsewhere (see also Table yielding coordinates defining the three dimensional structure of the crystalline complex. The structure of the ZAP- NC: 2 complex was determined by molecular replacement using the X-ray diffraction data for the ZAP-NC: 2 complex and the structure of the ZAP-NC: -1 complex as represented by the coordinates of Appendix I. Rigid body refinement was conducted using the ZAP-NC: 1 model. The resultant model was rebuilt by replacement of the 1 peptide with 2, followed by conventional refinement. The X-ray data of the ZAP-NC: -1 "dimeric" complex (two complexes per unit 1 0 cell) was also solved by molecular replacement using the ZAP-NC:?-1 ("monomer") structure. Rigid body refinement was conducted using the complete ZAP-NC:t-1 "monomeric" model, followed by rigid body refinement using individual SH2 domains and rebuilding of the helical domain region. Those structural coordinates are set forth in Protein Databank format in ****Appendix I (ZAP-NC:C-1 complex, "monmeric"), Appendix II ZAP-NC:C2 complex) and 1 5 Appendix III (ZAP-NC: -1 complex, "dimeric"), below. Such data may be transferred to any desired medium, and formatted as desired, for the practitioner's computer.

This invention encompasses those coordinates as well as any translation or rotation or the like thereof which maintains the internal coordinates, which maintains their intrinsic, internal relationship. Those skilled in the art will appreciate that the coordinates may be subjected to other transformations including, e.g. molecular mechanics calculations such as dynamic simulation, minimization, etc. This invention further encompasses the use of coordinates of ZAP-NC or the corresponding region of other ZAP family members, and in particular, the coordinates set forth in Appendix I, Appendix II or Appendix III, in conducting 25 such transformations (or more extensive transformations such as the generation of alternative conformations), as well as the products of such transformations derivatives of the coordinates).

IV. Modeling To illustrate the receptor site mapping approach, we used the Molecular Discovery suite of programs (Molecular Discovery Ltd; Goodford, P.J. "A Computational Procedure for Determining Energetically Favorable Binding Sites on Biologically Important Macromolecules" J. Med. Chem. 1985, 28, 849-857) on a Silicon Graphics Onyx workstation running Irix 5.2 to evaluate ZAP-NC as follows: The Protein Data Bank (PDB) coordinate file of ZAP-NC C1 was stripped of the i1 peptide and all crystallographically observed water molecules (using the Remove Atom feature of Sybil).

62 The resultant PDB file was merged with a set of molecular mechanics parameters that are suitable for the study of proteins. (Suitable such parameter sets include the user extensible data files which typically accompany the computer program.) A three-dimensional box that encapsulated the entire peptide binding face of each SH2 domain and the interfacial regions between the two domains was generated. The box dimensions were 60A x 40A x 37A, and a regular lattice of points positioned at o.5A intervals was designated to fill the box. The box position is illustrated in FIG. 6.

At each lattice point, 46 atomic and polyatomic probes were positioned sequentially. These probes encompass parameters that are representative of a large variety of chemical moieties.

•The energy of interaction between each probe with the protein was computed at each point of the lattice according to an empirical potential energy function that includes explicit terms for oooo 1 5 Lennard-Jones, electrostatic, and hydrogen-bonding potentials. The degree of burial for each •probe was computed by the method of images.

A binary contour map was generated, which can be used to visualize the sites of favorable interaction of a given probe at a given potential energy. An example is provided in FIG. 7.

Data from this receptor site mapping experiment were transfered to a DAT tape written in tar o format on a Silicon Graphics Onyx workstation running Irix 5.2. The map data uses the file extensions .cnt and .lont for the binary contour maps and the ASCII output, respectively. The orientation of the maps corresponds to our file zapNC-zl.pdb, which is in the Brookhaven o.e 25 Protein Databank format. The contour files are readable by Sybyl 6.1 (Tripos, Inc.. St. Louis, :eoe Filenames correspond to the probe nomenclature in the Molecular Discover Programmes, Version 12.

Information provided by site mapping via these or other programs as described in the Computational Methods section can be used to determine the spatial arrangement of potential pharmacophores, and thus provide the seed points for searches of 3-D databases or de Novo programs that attempt to grow from or link together the selected points. For an illustration of a pharmacophoric substructure for use in computational approaches, see e.g. Fesik (1993) cited elsewhere herein.

For example, the data defining binary contour maps may be displayed as 3D structures identifying preferred locations for selected functional groups using a software program such as Sybyl. By visual inspection of those displayed representations, one can select corresponding compounds containing moieties appropriately disposed with respect to each other such that they 63 coincide with preferred locations shown by the maps locations identified for each selected functional group characterized by favorable interaction energies with the target protein). Using computer programs such as LeapFrog one may "grow" a compound stochastically from one or more selected moieties located within appropriately mapped locations. Alternatively, starting with mapped favorable locations for two or more moieties, one may define"vectors" defining the spatial relationship between those moieties, and then use those vectors to select or design compounds embodying the selected moieties in the appropriate spatial relationship. Databases containing 3D structures of potential ligands contain experimentally determined or computationally generated structures. The selection or design process may be conducted with the 1 0 aid of computer using a programs such as ALADDIN (Van Drie et al, 1989, J Comput-Aided Mol Des 3, 225-251), MACCS-3D (Moock et al, 1990, Chemical Information Systems, (Eds, Bawden Mitchell, Chichester, pp 42-49), 3D SEARCH, ChemDBS-3D, SYBYL/3DB and CAVEAT. See Fesik, 1993, J Biomolecular NMR 3, 261-269.

15 V. Assays Binding Assays Competitive Binding Assays: Binding may be measured by competition using surface 2 0 plasmon resonance and allied technologies (Malmqvist, M. Current Opinions in 282-286; (1993); Malmqvist, Nature 361:186-187 (1993); Jonsson, U. and Malmqvist, Advances in Biosensors, JAI Press Ltd., London, 1992, pp. 291-336; Jonsson, U. et al., BioTechniques 11(5):620-627 (1991). SH2 domains are typically pre-incubated with various concentrations of test compound and the ability of the test compound to 2 5 competitively inhibit SH2 binding to an immobilized phosphopeptide ligand measured. Results are compared to binding measured in the absence of competitor and expressed as percent inhibition. IC50 values reflect the concentration of inhibitor required to reduce binding by Specifics of individual assays are described below. All asssays are run in HEPES Buffered Saline (HBS) composed of 10 mM HEPES (pH 7.4) /150 mM NaCI 3.4 mM EDTA 0.05% Tween 20 10 mM DTT at Primary Screen Test compound 50uM) is preincubated with the target SH2 in HBS mM DTT for a minimum of 1 hr at 4 0 C. The ability of the compound to inhibit binding of the SH2 domain to a target phosphopeptide is measured using SPR. Compounds that inhibit 3 5 SH2/phosphopetide association by a pre-determined increment are subjected to a secondary screen.

Secondary Screen Log dilutions of test compound (10-4 06, 10 are preincubated with the target SH2 in HBS 10 mM DTT. The ability of the compound to inhibit binding of the 64 SH2 domain to the target phosphopeptide is measured using SPR. IC50s are determined from the plot of per cent inhibition (compared to SH2 domain in the absence of inhibitor) vs. compound concentration.

Specifics of Tandem ZAP Assay A peptide corresponding to the (-chain ITAM-1 of the human T-cell receptor [NQLY(PO4)NELNLGRREEY(P04)DVLD] [SEQ ID NO 15] was synthesized as a part of a larger peptide [Ac-KGGNQLY(PO4)NELNLGRREEY-(PO 4

)DVLD-

NH2] [SEQ ID NO 16]and used to generate a ZAP-sensitive biosensor surface. Specifically, a Biosensor Chip CM5 was activated with 200 mM EDC 50 mM NHS to generate a surface 1 0 reactive to primary amines and the ITAM peptide immobilized through the N-terminal lysine. Unreacted sites were blocked with ethanolamine (1 M in water) and the chip cleaned of non-covalently bound peptide using 6 M guanidine hydrochloride. Assays were run in HBS 10 mM DTT using 10 nM pp70ZAP(1-259) test inhibitor.

S 1 5 Specifics of N-ZAP Assay: A peptide corresponding to the C-chain ITAM-1 of the human T-cell receptor [NQLYNELNLGRREEY(P0 4 )DVLD] [SEQ ID NO 17]was synthesized as a part of a larger peptide [Ac-KGGNQLYNELNLGRREEY-(PO4)DVLD-NH2J [SEQ ID NO 18] and used to generate a ZAP-sensitive biosensor surface as described above. Assays were run in HBS 10 mM DTT using pp70ZAP(1-259)R195K (a mutant where Arginine-195 is replaced by Lysine to inactivate the C-terminal SH2 domain) test inhibitor.

Specifics of C-ZAP Assay: A peptide corresponding to the C-chain ITAM-1 of the human T-cell receptor [NQLYNELNLGRREEY(P0 4 )DVLD] [SEQ ID NO 17] was synthesized as a part of a larger peptide [Ac-KGGNQLYNELNLGRREEY-(P04)DVLD-NH 2 [SEQ ID NO 2 5 18] and used to generate a ZAP-sensitive biosensor surface as described above. Assays were run in HBS 10 mM DTT using pp70ZAP(1-259)R37K (a mutant where Arginine- 37 is replaced by Lysine to inactivate the N-terminal SH2 domain) or pp70 Z A P (161test inhibitor.

Specifics of Tandem Syk Assay A pp 72 sy k peptide ligand corresponding to the 7chain ITAM of human FcERI [DGVY(PO4)TGLSTRNQETY(PO4)ETLK][SEQ ID NO 19] was synthesized as part of a larger peptide [Ac-CGGDGVY(P0 4 )TGLSTRNQETY-(P04)ETLK- NH2] [SEQ ID NO 20] and used to generate a Syk-sensitive biosensor surface. Specifically, a Biosensor Chip CM5 was activated with 200 mM ethyl-3-(3-dimethylaminopropyl)- 3 5 carbodiimide hydrochloride (EDC)/ 50 mM N-hydroxysuccinimide (NHS) to generate a surface reactive to primary amines; treated with ethylenediamine to generate a surface rich in primary amines; activated with m-maleimidobenzoyl-N-hydroxysuccinimide ester (sulfo-MBS; 50 mM in 25 mM NaHCO3) to generate a surface reactive to free thiols; and the ITAM peptide immobilized through the N-terminal cysteine. Unreacted sites were 65 blocked with P -mercaptoethanol and the chip cleaned of non-covalently bound peptide using 6 M guanidine hydrochloride. Assays were run in HBS using 20 nM pp 7 2 syk(1- 2 6 5 test inhibitor.

Specifics of C-Syk Assay A pp 72 sy k peptide ligand corresponding to a hemiphosphorylated y-chain ITAM of human FceRI [DGVY(P0 4 )TGLSTRNQETYETLK] was synthesized as part of a larger peptide [Ac-CGGDGVY(P04)TGLSTRNQETYETLK-NH2] and used to generate a C-Syk-sensitive biosensor surface as described above for tandem syk.

Assays were run in HBS using 270 nM pp 7 2 syk(1 63 2 6 5 test inhibitor.

Cell-based Assays T cell assay (T cell receptor-dependent transcription) Purpose and description of assay: This assay measures the ability of a compound to 1 5 inhibit TCR activation of the IL-2 transcription pathway in the human Jurkat T cell line. These Jurkat cells have been transfected with a construct containing the 0 -galactosidase gene under the control of an upstream promoter element, the NF-AT binding site, which normally regulates IL-2 production.

1 8 When cells are activated, 3 -galactosidase is produced.

20 Drug Treatment of Cells and Stimulation: The compounds to be assayed are serially diluted into assay buffer and each dilution is added to the Jurkat cells for a 1 hour preincubation. After the pre-incubation, the cells are transferred to plates coated with antibody to the CD3 component of the TCR. This antibody crosslinks the TCR, leading to activation of receptor signaling pathways. The cells are incubated for 4 hours, then the amount of p -gal 25 produced is measured.

Measurement of p -galactosidase: The assay is used to quantitate the amounts of p -galactosidase produced is the MUG assay. MUG, 4-methylumbelliferone galactose, is cleaved by p -galactosidase to form a fluorescent derivative, 7-hydroxy-4-methylcoumarin. The observed 3 0 fluorescence correlates with the amount of cleavage product, and thus with the amount of 0 -galactosidase. Production of P -gal without the addition of compound determines the 100% value for each well. The raw data is converted into "percent of control" triplicate wells are averaged, and then the data is plotted as of control release vs. concentration of test compound.

Cytotoxic T Lymphocyte killing Purpose and description of assay: This assay measures the ability of a compound to inhibit the cytolytic function of human cytotoxic lymphocyte lines. Human CD8 CTL were generated from mitogen-stimulated peripheral blood lymphocytes. Mitogen activated cells were grown in IL2 and re-stimulated every 3 weeks with antibodies directed against the T cell 66 receptor complex and CD8+ cells were sorted and cloned. Clone T9 was selected for use in the CTL assay. Since the T cells were selected nonspecifically, i.e. no specific antigen was used for induction, the target chosen for the assay was the B cell hybridoma OKT3. This cell line expresses anti-CD3 on its surface(an antibody against one of the subunits of the T cell receptor). The recognition of the T cell receptor by the antibody induces the cytolytic process of the target Drug Treatment of Cells and Stimulation: The compounds to be assayed are serially diluted into assay buffer and each dilution is added to the CTL's for a 1 hour pre-incubation.

1 0 After the pre-incubation, the cells are mixed with 5 1 Cr labelled OKT3 cells at a ratio of 3:1 (effector:target) and incubated for 3 hours. This ratio of effector to targets results in approximately 30% specific release.

Measurement of 5 1 Cr elease The cell mixture is centrifuged and the supernatant is 1 5 removed. The amount of 5 1 Cr released into the media is measured on a y counter and the specific release is determined using detergent lysed target cells as the 100% value. The data is plotted as specific release vs. concentration of test compound.

Animal Models: DELAYED TYPE HYPERSENSITIVITY An initial screening model is delayed type hypersensitivity. Mouse abdomens are painted with sensitizing chemicals (sensitization) such as dinitroflourobenzene or oxazalone. Seven days later the ears of sensitized mice are painted (challenge) with a lower concentration of the 2 5 compound. Antigen processing and presentation, T lymphocyte activation, leukocyte infiltration, humoral mediator release, increased microvascular permeability, and plasma exudation all result from challenge of sensitized mice and lead to edema formation. Edema presents as a twoto three- fold increase in ear thickness within twenty-four hours.

3 0 The test compounds or standards can be applied (topical or parenteral) at various times before or after the sensitization or challenge phases. Increased ear thickness is prevented by several compounds including immunosuppressive agents and steroids. This model is a primary model for contact dermatitis.

ALLOGENEIC SKIN TRANSPLANTATION An allogeneic skin transplant model is used to identify immunosuppressive activity of test compounds. In this model, donor mouse thoracic skin (Balb/c) is surgically grafted onto the thorax of recipient mice (C57bl/6). Host rejection of the graft is evidenced by erythema, drying out, and retraction of donor skin. The mean graft survival time is 10 to 11 days, with of the grafts being rejected by 12 days. Active novel immunosuppressive compounds, like existing immunosuppressive compounds, will prolong graft survival.

POPLITEAL LYMPH NODE HYPERPLASIA This model directly assesses T lymphocyte proliferation in vivo. Spleen cells, obtained from Balb/c mice, are isolated and administered into the foot pads of C3H mice. Within four days, the popliteal lymph nodes can be removed from the recipient mice and weighed. Other hematological assessments including FACS scanning for T lymphocyte subpopulations may also be performed.

Active compounds, like existing immunosuppressive compounds, will inhibit the increase in 1 0 node mass.

RHEUMATOID ARTHRITIS Several models are available for assessment of anti-arthritic activity, including adjuvantinduced, carageenan-induced, and collagen-induced arthritis in rats and/or mice. Paw pads are 1 5 injected with one of these agents. Paws increase in volume, and measurements are made between 20 and 30 days later. The ability of test compounds to prevent the induction of paw swelling is tested with daily treatment for 12 consecutive days following the injection of inducing agent.

The ability for the test compounds to reverse the progression of the paw swelling is tested by administration of the compound for 12 consecutive days beginning on the twelfth day following the injection of inducing agent. Paw swelling measurements are made by water displacement plethysmography. Histology is also an appropriate endpoint for these studies. The MRLIprmouse model, described above, is required for the rheumatoid arthritis indication. This model is a spontaneous autoimmune model that develops rheumatoid arthritis resembling the human condition, including the presence of circulating rheumatoid factor, pannus formation, and bone and cartilage erosion.

*99999 SYSTEMIC LUPUS ERYTHEMATOSUS Systemic lupus erythematosus is another autoimmune disease with several animal models.

Several murine strains develop spontaneous SLE. One such strain is MRL/Ipr-mice. These 3 0 mice, over time (20 to 30 weeks) develop auto-antibodies against dsDNA, nuclear antigens, and renal basement membrane. This leads to complement fixation and immune complex formation.

Damage to the kidney becomes apparent with the onset of proteinuria. Many of the other physiologic, hematologic, and immunologic aberrations described below for the CGVHD model are present. Immunosuppressive compounds such as cyclosporin, cyclophosphamide, and 3 5 leflunomide can prevent and reverse the course of disease in this model. Interestingly, these mice also develop pathologies akin to rheumatoid arthritis.

68 The murine chronic graft versus host disease model (CGVHD, described below) is a model of SLE that contains many of the clinical features of SLE. Activity in this model has been shown to be predictive of activity in the more clinically relevant SLE models.

TRANSPLANTATION

Allograft transplantation (skin graft) assay is often used as an initial test of immunosuppressive activity. While this model is useful as a screen, it may be supplemented with assays based on animal transplant models involving transplantation of internal organ (heart, liver, kidney, bone marrow) with use of "clinically acceptable" physiologic endpoints 1 0 to assess graft survival. Efficacy of test compounds in only a very limited number of these rodent models is required. Following observation of activity in a rodent model, the test .**:compounds are typically tested in further animal models canine, porcine or non-human primate). Active compounds decrease acute and chronic rejection and prolong transplant survival.

.o GRAFT VS. HOST DISEASE Chronic GVHD (CGVHD) can be used to model CD4+-dependent humoral immunity. It is induced in BDF 1 mice (which are progeny of DBA/2 male x C57BU6 female matings) by administering to them isolated spleen:lymph node cells from DBA/2 mice. This results in: a) disregulation and stimulation of CD4 T lymphocyte (Lyl murine marker) activity due to incompatibilities at MHC II molecules, and b) abnormal T-B lymphocyte cooperation. The resulting pathological state, in many ways, mimics systemic lupus erythematosus (SLE). Several measurable endpoints develop within 14 days; including, circulating anti-host IgG and IgE antibodies, altered T and B lymphocyte proliferation activity measured in vitro, complement utilization, 2 5 hemagglutination, slow progressive wasting, dermal aberrations, splenomegaly, lymphoid hyperplasia, and proteinuria. Only a few of these endpoints need to be measured. Active compounds are are those which limit T lymphocyte disregulation and abrogate changes in these variables. Many steroids prednisolone), cyclosporine, FK-506, cyclophosphamide, and leflunomide are all active in this model and can be used as positive controls The acute GVHD model (AGVHD) is also produced in BDF1 mice. In this case, isolated spleen:lymph node cells from C57BL/6 mice are administered. This results in disregulation and stimulation of CD8+ T lymphocytes due to incompatibilities in the MHC I molecules. Elevated cytokine levels and donor clonal expansion occurs. Ultimately, donor cytotoxic T lymphocytes 3 5 and NK cells rapidly reject host tissue and cause relatively rapid death of the recipient. The progression of AGVHD in this model is assessed by measurement of hematologic abnormalities (including T cell number and type), cytokine elevations (TNF, IL-1, IL-2, and/or IL-4), low body weight, hypoyglobulinemia, circulating hematologic characteristics indicative of aplastic anemia (granulocytopenia, thrombocytopenia), ex vivo NK or CTL activity, and host survival.

69 Active compounds are those which abrogate changes in the variables, and prolong survival over 4 to 6 weeks.

ASTHMA

Asthma offers another opportunity for safe immunosuppressive therapy. Atopic asthmatics have antibody mediated hypersensitivity and the often occurring late phase reaction is likened to a DTH response. Asthma has only recently been defined as an inflammatory disease (1992). Since then, several publications from prominent asthmatologists demonstrate the presence of activated CD4 and CD8 T lymphocytes in bronchoalveolar lavage fluid and blood of atopic 1 0 asthmatics. The ratios of these cells changes in asthmatic conditions. Furthermore, several of the T cell associated cytokines (IL-1, IL-2, IL-4, IL-5, and TNF) are all implicated in clinical and experimental asthma. Inflammatory events in asthma are now considered to be T lymphocyte driven. Initial clinical trials with inhaled cyclosporin suggest that local immunosuppression can ameliorate airway hyperreactivity the underlying defect in asthma.

S. The guinea pig model of antigen-induced pulmonary aberrations is used as a model for asthma.

These animals are actively sensitized to ovalbumin to generate high circulating titers of antiovalbumin antibody with seroconversion to the IgE class, as is the case with atopic asthmatics.

Aerosol challenge of sensitized guinea pigs results in measurable eosinophil rich pulmonary infiltrates (approximately a 16-fold increase in eosinophils), pulmonary edema, and mucous plugging of the small airways; all culminating in the expression of the underlying defect in asthma- airway hyperreactivity (approximately a 3 to 4-fold increase in reactivity). Acute bronchoconstriction is obviously present and points the aforementioned presence of the pathophysiologic sequelae. Active compounds are those which lessen or abrogate such symptoms.

The above description is meant to illustrate, rather than limit the scope of the invention. Given the foregoing description, numerous variations in the materials or methods employed in performing the invention will be obvious to one skilled in the art. Any such obvious variation is to be considered within the scope of the invention.

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72 Page~) w -sareclaims pages They appear after the appendix(es) CknA Ar'c Appendix 1: Coordinates for the 3D structure of ZAP-NC:z1* REMARK FILENAME='test-slowpdb" REMARK TOPH19.pep -MACRO for protein sequence created by user: marcos Atom Atom amino acid type residue temp, x v z occ factor a a

ATOM

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25 ATOM

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

CB

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C

0 HT1 HT2

N

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CA

N

CD

CA

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C

0

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3 -1.489 3 -2.232 3 -2.949 3 -2.094 3 -1.755 3 -0.595 3 -0.506 3 -1.947 3 -1.527 3 -1.707 3 -2.095 4 -2.771 4 -4.186 4 -2.640 4 -4.058 4 -4.895 4 -1.652 4 -1.211 5 -1.333 5 -1.777 -4.706 -3.399 -3.304 -2.461 -4.886 -4.867 -6.812 -7 .433 -6.899 -7 .382 -5.522 -4.385 -4 .460 -3.739 -3 .243 -4.275 -2 .579 -2.170 -2 .029 -2 .325 -0 .905 0.206 -1.261 -0 .442 -2 .504 -3 .137 -2 .958 -4 .443 -2 .679 -2 .485 36.906 37.163 38.181 36.353 34.408 34.003 35.572 34.967 35.753 36.652 35.754 33.690 34.087 32.379 32.113 32 .774 32.341 31.265 33.509 34.322 33.592 34.437 34.121 34.064 34.553 34.469 35.124 35.462 34.296 34.847 1.00 37.30 1.00 38.04 1.00 39.49 1.00 34.64 1.00 34.63 1.00 34.56 1.00 0.00 1.00 0.00 1.00 40.12 1.00 0.00 1.00 36.56 1.00 31.82 1.00 32.51 1.00 29.95 1.00 30.71 1.00 31.34 00 28.61 1.00 -30.48 1.00 25.13 1.00 0.00 1.00 21.95 1.00 20.80 1.00 20.21 1.00 19.51 1.00 19.03 1.00 0.00 1.00 18.99 1.00 22.76 1.00 16.60 1.00 14.22 -0 .411 -1 .029 0.973 1. 884 1.151 0.413 2 .422 2.339 3 .674 4.755 73 ATOM 31 N HIS 7 ATM 1 N IS 73.527 -2.665 32.977 1.00 15.98 ATOM 32 H HIS 7 2.628 -2.813 32.643 1.00 0.00 ATOM 33 CA HIS 7 4.660 -2.422 32.091 1.00 16.26 ATOM 34 CB HIS 7 4.424 -3.096 30.736 1.00 16.78 ATOM 35 CG HIS 7 3.194 -2.622 30.027 1.00 16.42 ATOM 36 CD2 HIS 7 3.033 -1.729 29.021 1.00 16.56 ATOM 37 ND1 HIS 7 1.933 -3.092 30.324 1.00 15.90 ATOM 38 HD1 HIS 7 1.674 -3.788 30.967 1.00 0.00 ATOM 39 CEl HIS 7 1.049 -2.511 29.534 1.00 16.52 ATOM 40 NE2 HIS 7 1.692 -1.681 28.734 1.00 17.76 ATOM 41 HE2 HIS 7 1.276 -1.120 28.048 1.00 0.00 ATOM 42 C HIS 7 5.014 -0.943 31.891 1.00 17.19 ATOM 43 0 HIS 7 6.082 -0.629 31.357 1.00 18.03 0ATOM 44 N LEU 8 4.125 -0.038 32.300 1.00 14.61 1 15 ATOM 45 H LEU 8 3.316 -0.310 32.782 1.00 0.00 **ATOM 46 CA LEU 8 4.382 1.393 32.143 1.00 14.75 ATOM 47 CB LEU 8 3.106 2.216 32.371 1.00 15.09 *ATOM 48 CG LEt) 8 2.051 2.374 31.267 1.00 19.47 ATOM 49 CD1 LEt) 8 2.669 2.167 29.891 1.00 21.37 ATOM 50 CD2 LEt) 8 0.911 1.417 31.472 1.00 23.01 ATOM 51 C LEU 8 5.481 1.879 33.085 1.00 13.31 00 ATOM 52 0 LEU 8 5.432 1.628 34.288 1.00 13.01 ATOM 53 N PRO 9 6.478 2.609 32.551 1.00 13.43 *ATOM 54 CD PRO 9 6.691 2.982 31.141 1.00 13.38 25 ATOM 55 CA PRO 9 7.571 3.113 33.385 1.00 12.50 ATOM 56 CB PRO 9 8.523 3.736 32.363 1.00 12.42 ATOM 57 CG PRO 9 7.617 4.159 31.267 1.00 14.81 ATOM 58 C PRO 9 7.117 4.122 34.440 1.00 10.81 ATOM 59 0 PRO 9 7.783 4.297 35.459 1.00 12.13 ATOM 60 N PHE 10 5.985 4.776 34.200 1.00 11.91 ATOM 61 H PHE 10 5.502 4.601 33.371 1.00 0.00 ATOM 62 CA PHE 10 5.451 5.761 35.140 1.00 11.80 ATOM 63 CB PHE 10 4.981 7.029 34.406 1.00 10.49 ATOM 64 CG PHE 10 4.009 6.769 33.289 1.00 12.16 ATOM 65 CD1 PHE 10 2.642 6.722 33.536 1.00 11.91 ATOM 66 CD2 PHE 10 4.460 6.579 31.985 1.00 12.16 ATOM 67 CE1 PHE 10 1.738 6.492 32.505 1.00 14.05 ATOM 68 CE2 PHE 10 3.561 6.348 30.949 1.00 11.03 ATOM 69 C Z PHE 10 2.198 6.305 31.210 1.00 10.40 74 ATOM 70 C PHE 10 4.348 5.220 36.063

S

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ATOM

ATOM

71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 O PHE N PHE H PHE CA PHE CB PHE CG PHE CD1 PHE CD2 PHE CE1 PHE CE2 PHE CZ PHE C PHE O PHE N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CE1 TYR CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR C TYR O TYR N GLY H GLY CA GLY C GLY O GLY N SER H SER 10 11 11 11 11 11 11 11 11 11 11 11 11 12 12 12 12 12 12 12 12 12 12 12 12 12 12 13 13 13 13 13 14 14 14 14 14 14 3.648 4.172 4.752 3.179 2.539 1.602 0.374 1.949 -0.497 1.083 -0.141 3.904 4.890 3.421 2.645 4.050 4.154 5.234 5.079 6.098 6.432 7.444 7.275 8.296 8.048 3.398 3.909 2.278 1.920 1.597 0.762 0.266 0.635 1.068 -0.167 -0.680 -1.532 -1.068 5.994 3.901 3.312 3.263 2.060 1.266 1.787 -0.011 1.046 -0.759 -0.230 2.819 2.084 3.279 3.868 2.962 4.229 5.165 5.911 6.737 5.275 6.094 6.821 7.629 7.993 1.856 1.466 1.340 1.683 0.284 0.814 1.940 0.010 -0.867 0.356 -0.931 -0.657 -0.007 36.714 36.085 35.559 36.944 36.241 37.119 37.504 37.548 38.301 38.345 38.722 38.214 38.157 39.360 39.342 40.628 41.471 40.994 39.829 39.371 41.688 41.242 40.086 39.659 38.798 41.436 42.483 40.950 40.111 41.669 42.818 42.769 43.865 43.854 45.027 45.685 46.784 47.331 1.00 10.35 1.00 9.59 1.00 10.23 1.00 0.00 1.00 9.09 1.00 8.78 1.00 8.82 1.00 9.98 1.00 12.08 1.00 10.58 1.00 11.57 1.00 10.29 1.00 10.01 1.00 10.38 1.00 8.54 1.00 0.00 1.00 7.85 1.00 9.01 1.00 9.41 1.00 11.88 1.00 10.68 1.00 10.27 1.00 10.04 1.00 10.17 1.00 14.36 1.00 0.00 1.00 8.85 1.00 9.35 1.00 11.20 1.00 0.00 1.00 12.09 1.00 12.99 1.00 12.85 1.00 12.55 1.00 0.00 1.00 14.38 1.00 13.42 1.00 21.30 1.00 0.00 75 ATOM 109 C SER 14 0.542 1.232 46.060 1.00 15.49 ATOM 110 0 SER 14 0.894 0.760 47.144 1.00 18.54 ATOM 111 N ILE 15 0.748 2.506 45.737 1.00 14.76 ATOM 112 H ILE 15 0.428 2.829 44.869 1.00 0.00 ATOM 113 CA ILE 15 1.390 3.423 46.676 1.00 12.31 ATOM 114 CB ILE 15 2.571 4.210 46.040 1.00 12.37 ATOM 115 CG2 ILE 15 3.712 3.256 45.687 1.00 13.51 ATOM 116 CG1 ILE 15 2.101 5.014 44.827 1.00 11.08 ATOM 117 CD ILE 15 3.131 6.016 44.347 1.00 12.11 ATOM 118 C ILE 15 0.354 4.398 47.226 1.00 10.69 ATOM 119 O ILE 15 -0.750 4.488 46.701 1.00 11.71 ATOM 120 N SER 16 0.700 5.099 48.299 1.00 8.45 ATOM 121 H SER 16 1.588 5.018 48.689 1.00 0.00 ATOM 122 CA SER 16 -0.219 6.053 48.899 1.00 12.16 15 ATOM 123 CB SER 16 0.073 6.199 50.393 1.00 8.73 ATOM 124 OG SER 16 1.380 6.711 50.597 1.00 11.59 ATOM 125 HG SER 16 1.483 6.783 51.560 1.00 0.00 **ATOM 126 C SER 16 -0.073 7.411 48.225 1.00 11.37 **ATOM 127 O SER 16 0.883 7.640 47.474 1.00 10.80 ATOM 128 N ARG 17 -1.006 8.315 48.509 1.00 10.26 ATOM 129 H ARG 17 -1.743 8.056 49.105 1.00 0.00 **ATOM 130 CA ARG 17 -0.944 9.657 47.947 1.00 8.92 ATOM 131 CB ARG 17 -2.148 10.492 48.385 1.00 9.48 ATOM 132 CG ARG 17 -2.033 11.962 47.998 1.00 8.28 ATOM 133 CD ARG 17 -3.228 12.766 48.448 1.00 8.69 ATOM 134 NE ARG 17 -4.417 12.388 47.701 1.00 8.47 ATOM 135 HE ARG 17 -4.400 11.503 47.308 1.00 0.00 ATOM 136 CZ ARG 17 -5.470 13.173 47.505 1.00 10.19 ATOM 137 NH1 ARG 17 -5.499 14.402 48.002 1.00 10.59 ATOM 138 HH11 ARG 17 -4.717 14.750 48.520 1.00 0.00 ATOM 139 HH12 ARG 17 -6.295 14.988 47.859 1.00 0.00 ATOM 140 NH2 ARG 17 -6.490 12.734 46.789 1.00 8.14 ATOM 141 HH21 ARG 17 -6.457 11.804 46.413 1.00 0.00 ATOM 142 HH22 ARG 17 -7.292 13.305 46.629 1.00 0.00 ATOM 143 C ARG 17 0.342 10.321 48.426 1.00 11.05 ATOM 144 O ARG 17 1.039 10.974 47.649 1.00 12.01 ATOM 145 N ALA 18 0.666 10.131 49.704 1.00 9.21 ATOM 146 H ALA 18 0.067 9.605 50.279 1.00 0.00 ATOM 147 CA ALA 18 1.872 10.708 50.286 1.00 11.20 76 ATOM 148 CB ALA 18 2.001 10.301 51.745 1.00 15.06 O6S* S. 4 *5SS *5 S S

S.

S S 5555 *5 S S 5 .5*

S

S

5* 5*

S

S

S..

1 0 I0 1 5

A

A

A

20 A

A

A

A

25 A

A

A

A

A

A'

A

A

A

A

A

A

A

A

A

ATOM 149 ATOM 150 ATOM 151 ATOM 152 ATOM 153 ATOM 154 ATOM 155 ATOM 156 ATOM 157 ATOM 158 ATOM 159 ATOM 160 ATOM 161 TOM 162 TOM 163 %TOM 164 TOM 165 TOM 166 TOM 167 TOM 168 TOM 169 TOM 170 TOM 171 TOM 172 TOM 173 TOM 174 TOM 175 TOM 176 TOM 177 TOM 178 TOM 179 TOM 180 TOM 181 TOM 182 TOM 183 TOM 184 'OM 185 TOM 186

C

0

N

H

CA

CB

CG

CD

OEI

OE2

C

0

N

H

CA

CB

C

0

N

H

CA

CB

CG

CD

OE1 OE2

C

0

N

H

CA

CB

CG

CD

OEl OE2

C

0

ALA

ALA

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

ALA

ALA

ALA

ALA

ALA

ALA

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

18 18 19 19 19 19 19 19 19 19 19 19 20 20 20 20 20 20 21 21 21 21 21 21 21 21 21 21 22 22 22 22 22 22 22 22 22 3.123 3.959 3.250 2.542 4.403 4.364 4.482 4.358 5.400 3.216 4.449 5.524 3.280 2.463 3.177 1.730 3.679 4.466 3.243 2.638 3.652 2.804 1.349 0.488 -0.692 0.985 5.142 5.780 5.706 5 .162 7 .124 7 .454 8 .811 9.194 8.324 10.371 7.942 8.902 10.303 11.152 9.008 8.381 8.488 6.960 6.297 4.790 4.108 4.285 9.043 9.357 9.155 8.875 9.681 9.596 11.127 11.494 11.933 11.588 13.328 14.091 14.202 15.002 15.230 15.414 13.468 14.425 12.487 11.739 12.508 11.396 11.551 10.364 9.852 9.948 12.345 13.080 49.521 49.193 49.240 49.517 48.514 48.465 49.820 49.742 49.647 49.774 47.099 46.584 46.472 46.939 45.109 44.616 45.052 44.175 46.009 46.693 46.071 47.082 46.656 47 .625 47.308 48.693 46.374 45.942 47.073 47.388 47.394 48.389 49.035 49.891 50.631 49.818 46.107 45.873 1.00 12.57 1.00 12.90 1.00 11.57 1.00 0.00 1.00 11.99 1.00 13.36 1.00 20.61 1.00 21.71 1.00 29.81 1.00 19.69 1.00 11.13 1.00 12.79 1.00 12.51 1.00 0.00 1.00 13.22 1.00 10.29 1.00 11.20 1.00 11.31 1.00 10.24 1.00 0.00 1.00 10.86 1.00 7.73 1.00 8.58 1.00 10.14 1.00 9.72 1.00 13.94 1.00 12.31 1.00 13.09 1.00 13.22 1.00 0.00 1.00 11.25 1.00 16.27 1.00 25.51 1.00 32.11 1.00 36.02 1.00 34.67 1.00 11.86 1.00 10.75 77 goo* Go0* *a *0 S ATOM 187 ATOM 188 ATOM 189 ATOM 190 ATOM 191 ATOM 192 ATOM 193 ATOM 194 ATOM 195 ATOM 196 ATOM 197 ATOM 198 ATOM 199 ATOM 200 1 5 ATOM 201 ATOM 202 ATOM 203 ATOM 204 ATOM 205 ATOM 206 ATOM 207 ATOM 208 ATOM 209 ATOM 210 25 ATOM 211 ATOM 212 ATOM 213 ATOM 214 ATOM 215 ATOM 216 ATOM 217 ATOM 218 ATOM 219 ATOM 220 ATOM 221 ATOM 222 ATOM 223 ATOM 224 ATOM 225 N HIS H HIS CA HIS CB HIS CG HIS CD2 HIS ND1 HIS HD1 HIS CEl HIS NE2 HIS HE2 HIS C HIS O HIS N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS 0 LYS N LEU H LEU CA LEU CB LEU 7 .537 6.741 8.226 7.651 8.087 9 .315 7.205 6.236 7.873 9 .156 9 .898 8.156 9.148 6.986 6 .232 6 .792 5.309 4.393 2 .935 4 .724 7 .636 8.165 7.790 7 .347 8.595 8 .465 7 .135 7 .109 5 .794 5.858 6.621 6 .068 4.953 10.051 10.728 10.518 9 .913 11.906 12.231 10.889 11. 162 9.927 8. 634 8.090 7.746 7.854 6.713 6.898 6.306 12.361 12.708 12.992 12.680 14.159 14.532 13 .515 13.881 13 .449 15.343 16.110 15.472 14.841 16.548 16.587 17.068 16.971 17.436 17.440 18.081 16.480 17.769 16.323 17 .226 15.096 14.405 14.746 13-357 45.512 43.987 43.286 43.903 44. 050 44.482 44.576 44.960 44.711 44. 998 43.045 42.394 42.978 43.521 42.117 42.046 41. 350 41. 539 39.874 42.599 41. 790 43 .914 44.523 44.480 46.001 46.517 48 .018 48.586 50.075 50. 375 50. 403 50.472 44.12 5 43.634 44. 334 44.690 44. 057 44.618 1.00 0.00 1.00 9.26 1.00 7.86 1.00 10.39 1.00 8.91 1.00 14.23 1.00 0.00 1.00 10.97 1.00 13.67 1.00 0.00 1.00 10.69 1.00 10.64 1.00 10.63 1.00 0.00 1.00 10.53 1.00 10.68 1.00 11.63 1.00 9.03 1.00 7.43 1.00 11.35 1.00 11.67 1.00 11.16 1.00 0.00 1.00 10.68 1.00 9.16 1.00 6.98 1.00 8.43 1.00 9.56 1.00 9.88 1.00 0.00 1.00 0.00 1.00 0.00 1.00 12.70 1.00 15.29 1.00 14.74 1.00 0.00 1.00 16.13 1.00 13.92 11.406 45.255 1.00 9.76 @4S5 Se C. S

OSSS

S 0 0 100055 0 78 ATOM 226 CG LEU 26 12.231 13.216 46.145 1.00 13.80 ATOM 227 CD1 LEU 26 12.430 11.772 46.521 1.00 16.36 ATOM 228 CD2 LEU 26 13.320 14.072 46.761 1.00 17.12 ATOM 229 c LEU 26 12.252 14.818 42.574 1.00 18.06 ATOM 230 0 LEU 26 13.427 14.852 42.207 1.00 19.38 ATOM 231 N ALA 27 11.226 14.853 41.730 1.00 19.46 ATOM 232 H ALA 27 10.312 14.818 42.076 1.00 0.00 ATOM 233 CA ALA 27 11.414 14.926 40.285 1.00 20.96 ATOM 234 CB ALA 27 10.309 14.154 39.576 1.00 19.82 ATOM 235 c ALA 27 11.495 16.356 39.741 1.00 20.81 ATOM 236 o ALA 27 11.713 16.551 38.544 1.00 24.10 ATOM 237 N GLY 28 11.285 17.352 40.596 1.00 20.02 ATOM 238 H GLY 28 11.099 17.182 41.546 1.00 0.00 ATOM 239 CA GLY 28 11.369 18.723 40.132 1.00 19.49 ATOM 240 C GLY 28 10.100 19.554 40.161 1.00 21.05 ATOM 241 0 GLY 28 10.164 20.764 39.955 1.00 22.70 ***ATOM 242 N SEN 29 8.946 18.926 40.374 1.00 20.23 ATOM 243 H SEN 29 8.927 17.952 40.496 1.00 0.00 ATOM 244 CA SEM 29 7.669 19.650 40.438 1.00 21.17 ATOM 245 CB SEN 29 7.641 20.595 41.645 1.00 24.34 ATOM 246 CG SEN 29 7.505 19.914 42.994 1.00 28.45 *ATOM 247 A SEN 29 5.834 18.935 43.183 1.00 33.82 ATOM 248 CE SEN 29 4.660 20.332 43.772 1.00 30.42 ATOM 249 C SEN 29 7.311 20.438 39.177 1.00 19.69 25 ATOM 250 0 SEN 29 6.640 21.471 39.250 1.00 18.65 *ATOM 251 N ALA 30 7.749 19.948 38.025 1.00 19.92 ATOM 252 H ALA 30 8.251 19.114 38.032 1.00 0.00 ATOM 253 CA ALA 30 7.459 20.612 36.760 1.00 20.38 ATOM 254 CB ALA 30 8.314 20.023 35.641 1.00 20.76 ATOM 255 C ALA 30 5.985 20.454 36.428 1.00 21.88 ATOM 256 0 ALA 30 5.346 19.494 36.857 1.00 22.02 ATOM 257 N ASP 31 5.434 21.423 35.705 1.00 21.51 ATOM 258 H ASP 31 5.990 22.173 35.411 1.00 0.00 ATOM 259 CA ASP 31 4.034 21.367 35.304 1.00 22.50 ATOM 260 CB ASP 31 3.582 22.700 34.704 1.00 26.22 ATOM 261 CG ASP 31 3.559 23.818 35.723 1.00 32.04 ATOM 262 ODi ASP 31 2.465 24.354 35.985 1.00 38.46 ATOM 263 002 ASP 31 4.632 24.163 36.265 1.00 39.17 ATOM 264 C ASP 31 3.897 20.263 34.271 1.00 18.87 79 ATOM 265 0 ASP 31 4.762 20.106 33.407 1.00 18.52

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303

GLY

LEU

LEU

CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N PHE H PHE CA PHE CB PHE CG PHE CD1 PHE CD2 PHE CE1 PHE CE2 PHE CZ PHE C PHE O PHE N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N LEU H LEU CA LEU N GLY H GLY CA GLY C GLY 2.826 2.174 2.609 3.263 3.047 4.079 4.234 4.746 5.765 6.585 7.603 7.278 3.648 2.833 3.625 4.305 2.581 1.410 1.713 1.269 2.460 1.567 2.762 2.314 3.050 4.097 2.240 1.413 2.522 3.428 2.980 2.063 4.209 1.190 0.153 1.209 2.057 0.000 19.488 19.611 18.403 17.108 16.073 17.159 18.007 15.965 16.359 15.272 14.664 15.869 15.093 15.582 13.810 13.484 12.918 12.877 12.111 10.798 12.694 10.078 11.985 10.671 11.494 11.083 10.738 11.119 9.336 9.168 9.520 8.438 9.637 8.615 9.251 7.297 6.836 6.502 34.376 35.099 33.445 33.890 33.263 34.942 35.398 35.470 36.545 37.248 36.297 38.461 36.078 36.868 35.726 35.098 36.224 35.225 33.955 33.796 32.934 32.640 31.776 31.628 36.462 35.967 37.197 37.565 37.470 38.701 40.123 40.681 41.002 37.637 37.855 37.498 37.350 37.626 1.00 17.28 1.00 0.00 1.00 15.03 1.00 15.03 1.00 18.44 1.00 15.47 1.00 0.00 1.00 14.99 1.00 14.41 1.00 15.28 1.00 14.45 1.00 12.37 1.00 13.99 1.00 12.54 1.00 13.31 1.00 0.00 1.00 13.12 1.00 10.40 1.00 13.52 1.00 13.58 1.00 10.22 1.00 14.14 1.00 12.23 1.00 13.01 1.00 11.75 1.00 12.17 1.00 11.21 1.00 0.00 1.00 8.87 1.00 8.10 1.00 8.50 1.00 9.19 1.00 6.81 1.00 7.92 1.00 8.48 1.00 8.12 1.00 0.00 1.00 8.05 80 a 15

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 CB LEU CG LEU CD1 LEU CD2 LEU C LEU 0 LEU N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NH1 ARG ATOM 320 HH11 ARG ATOM 321 HH12 ARG ATOM 322 NH2 ARG ATOM 323 HH21 ARG ATOM 324 HH22 ARG ATOM 325 C ARG ATOM 326 0 ARG ATOM 327 N GLN ATOM 328 H GLN ATOM 329 CA GLN ATOM 330 CB GLN ATOM 331 CG GLN ATOM 332 CD GLN ATOM 333 OE1 GLN ATOM 334 NE2 GLN ATOM 335 HE21 GLN ATOM 336 HE22 GLN ATOM 337 C GLN ATOM 338 0 GLN ATOM 339 N CYS ATOM 340 H CYS ATOM 341 CA CYS ATOM 342 CB CYS -0.258 -1.676 -2.635 -1.716 0.164 1.238 -0.887 -1.714 -0.853 -0.583 -1.508 -0.974 -1.722 -1.529 -2.647 -2.956 -2.500 -3.658 -3.236 -2.988 -3.915 -2.166 -3.161 -2.150 -1.324 -3.353 -2.996 -4.203 -3.832 -2.998 -4.463 -5.116 -4.267 -4.293 -3.848 -5.589 -5.895 -6.569 -7.918 5.734 5.210 6.386 4.348 5.532 4.961 5.380 5.882 4.468 5.229 6.396 7.196 8.428 9.196 8.577 7.567 6.681 7.697 9.751 10.517 9.870 3.706 4.125 2 .547 2.268 1.735 0.311 -0.585 -1.990 -2.195 -2.968 -2.694 -3.889 2.359 2.856 2.339 1.887 2.909 3.079 36.327 36.089 35.956 34.832 38.789 38.991 39.581 39.404 40.716 42.015 42.282 43.451 43.678 43.101 44.617 45.423 45.337 46.120 44.775 44.184 45.480 40.783 40.193 41.432 41.866 41.549 41.974 42.170 42.590 43 .472 41.967 41.275 42.210 42.565 43 .594 42.278 41.464 43.194 42.496 1.00 9.30 1.00 15.30 1.00 15.10 1.00 17.89 1.00 8.05 1.00 8.20 1.00 8.30 1.00 0.00 1.00 8.39 1.00 6.96 1.00 6.89 1.00 10.99 1.00 8.74 1.00 0.00 1.00 10.85 1.00 9.35 1.00 0.00 1.00 0.00 1.00 8.78 1.00 0.00 1.00 0.00 1.00 6.82 1.00 8.12 1.00 8.06 1.00 0.00 1.00 9.21 1.00 13.08 1.00 18.32 1.00 18.70 1.00 19.47 1.00 22.25 1.00 0.00 1.00 0.00 1.00 10.19 1.00 12.74 1.00 11.02 1.00 0.00 1.00 12.42 1.00 9.94 81 0

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 0 ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381

SG

C

0

N

H

CA

CB

CG

CD1 CD2

C

0

N

H

CA

CB

CG

CD

NE

HE

CZ

CYS

CYS

CYS

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

-9.205 -6.720 -6.736 -6.776 -6.680 -6.934 -6.139 -4.629 -4.020 -3.969 -8.401 -8.748 -9.269 -8.957 -10.690 -11.185 -10.390 -10.855 -10.749 -9.859 -11.774 -12.996 -13.161 -13.760 -11.582 -10.666 -12.355 -11.603 -12.672 -11.210 -10.362 -12.032 -12.471 -11.357 -11.715 -11.298 -10.080 -12.054 -13.012 3.852 2. 008 0.782 2. 620 3.598 1.875 2.543 2.680 3.500 1.317 1.789 1.127 2.412 2.869 2.431 3.872 4.754 6.190 6.723 6.768 7.178 7.177 6.844 7.526 7 .602 7.569 7.948 1.636 1.203 1.472 1. 815 0.738 1.660 2.145 2.592 -0.476 -0.598 -1.394 -1.234 43.504 44.414 44.291 45.592 45.633 46.833 47.965 47.747 48.863 47.657 47.226 48.201 46.439 45.631 46.758 46.820 47.756 47.675 46.321 45.924 45.612 46.121 47.050 45.579 44.373 43.973 43.842 45.846 46.274 44.589 44.255 43.637 42.496 41.768 40.982 43.080 43.220 42.490 42.420 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 i. 00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 12.92 12.91 13.19 10.63 0.00 12.90 11.53 13.24 12.45 12.54 11.01 12.23 10.95 0.00 12 .13 10.86 10.97 14.51 13 .81 0.00 16.54 18.89 0.00 0.00 21.20 0.00 0.00 13.35 14.24 14.81 0.00 15.10 16.52 17.93 0.00 15.55 16.20 15.52 0.00 NH1 ARG HH11 ARG HH12 ARG NH2 ARG HH21 ARG HH22 ARG C ARG O ARG N SER H SER CA SER CB SER OG SER HG SER C SER O SER N LEU H LEU 82 ATOM 382 CA LEU 43 -11.484 -2.600 41.904 1.00 16.45

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N GLY H GLY CA GLY C GLY O GLY N GLY H GLY CA GLY C GLY O GLY N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CE1 TYR CD2 TYR CE2 TYR CZ TYR -12.504 -12.877 -13.998 -11.661 -11.064 -11.874 -9.786 -9.170 -9.267 -9.138 -8.965 -9.188 -9.242 -9.075 -7.666 -6.795 -7.443 -8.185 -6.137 -5.426 -5.110 -4.019 -3.758 -5.931 -5.678 -4.592 -4.362 -5.246 -6.340 -7.472 -5.243 -4.355 -5.298 -5.092 -5.205 -6.117 -4.180 -3.044 -3.741 -4.324 -5.333 -4.976 -2.319 -1.871 -2.542 -2.822 -2.324 -0.875 -0.602 0.048 -0.234 1.459 1.983 1.292 3.220 3.734 3.859 3.889 2.528 1.793 0.514 1.952 0.674 -0.037 -1.311 -1.670 5.290 5.747 5.967 5.549 7.365 7.619 9.113 6.867 8.045 7.561 41.923 43.285 43.111 43.916 40.470 39.657 40.184 40.896 38.846 38.411 37.222 39.368 40.305 39.044 39.226 39.766 38.800 38.409 38.914 37.548 36.977 37.440 36.960 36.010 35.525 36.007 35.554 35.351 39.376 39.525 39.679 39.641 40.057 41.573 41.861 42.390 39.286 39.261 1.00 19.56 1.00 21.50 1.00 22.99 1.00 21.68 1.00 15.54 1.00 16.36 1.00 15.64 1.00 0.00 1.00 16.00 1.00 15.01 1.00 16.12 1.00 12.81 1.00 0.00 1.00 10.47 1.00 9.12 1.00 9.20 1.00 9.58 1.00 0.00 1.00 10.00 1.00 10.79 1.00 12.05 1.00 11.46 1.00 10.52 1.00 13.57 1.00 13.97 1.00 14.16 1.00 15.79 1.00 0.00 1.00 9.80 1.00 9.96 1.00 9.60 1.00 0.00 1.00 9.96 1.00 9.82 1.00 7.41 1.00 10.33 1.00 8.75 1.00 6.17 r ATOM 411 ATOM 412 ATOM 413 ATOM 414 ATOM 415 ATOM 416 ATOM 417 ATOM 418 ATOM 419 ATOM 420

OH

HH

C

O

N

H

CA

CB

CG1 CG2

C

O

TYR

TYR

TYR

TYR

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

83 ATOM 421 N LEU 48 -4.536 9.117 38.590 1.00 9.67 ATOM 422 H LEU 48 -5.470 9.398 38.591 1.00 0.00 ATOM 423 CA LEU 48 -3.585 9.907 37.827 1.00 10.81 ATOM 424 CB LETJ 48 -4.275 10.520 36.604 1.00 14.82 ATOM 425 CG LEU 48 -3.499 10.808 35.312 1.00 18.26 ATOM 426 CD1 LEU 48 -4.357 11.691 34.420 1.00 19.66 ATOM 427 CD2 LEU 48 -2.178 11.482 35.582 1.00 16.76 ATOM 428 C LEU 48 -3.174 11.022 38.786 1.00 9.47 ATOM 429 0 LEU 48 -4.020 11.754 39.302 1.00 9.86 ATOM 430 N SER 49 -1.888 11.119 39.064 1.00 8.65 ATOM 431 H SEP. 49 -1.257 10.496 38.640 1.00 0.00 ATOM 432 CA SEP. 49 -1.386 12.145 39.956 1.00 12.04 ATOM 433 CB SEP. 49 -0.590 11.479 41.084 1.00 13.48 ATOM 434 OG SEP. 49 -0.103 12.428 42.009 1.00 30.10 1 ATOM 435 HG SEP. 49 0.614 12.893 41.557 1.00 0.00 ATOM 436 c SER 49 -0.510 13.088 39.125 1.00 10.25 ATOM 437 0 SEP. 49 0.481 12.655 38.537 1.00 11.37 ATOM 438 N LEU 50 -0.888 14.361 39.040 1.00 12.50 ATOM 439 H LEU 50 -1.689 14.672 39.504 1.00 0.00 20 ATOM 440 CA LEt) 50 -0.114 15.319 38.252 1.00 13.14 ATOM 441 CB LEt) 50 -0.803 15.591 36.906 1.00 14.83 SATOM 442 CG LEt) 50 -2.188 16.241 36.861 1.00 18.60 ATOM 443 CD1 LEU 50 -2.066 17.749 36.713 1.00 18.66 ATOM 444 CD2 LEU 50 -2.959 15.691 35.681 1.00 22.06 25 ATOM 445 C LEU 50 0.181 16.629 38.973 1.00 14.34 *ATOM 446 0 LEU 50 -0.481 16.982 39.951 1.00 14.49 ATOM 447 N VAL 51 1.190 17.339 38.481 1.00 13.90 ATOM 448 H VAL 51 1.680 17.006 37.698 1.00 0.00 ATOM 449 CA VAL 51 1.591 18.615 39.052 1.00 14.39 ATOM 450 CB VAL 51 3.124 18.688 39.277 1.00 13.58 ATOM 451 CG1 VAL 51 3.512 20.051 39.833 1.00 12.21 ATOM 452 CG2 VAL 51 3.581 17.592 40.218 1.00 12.91 ATOM 453 C VAL 51 1.218 19.757 38.111 1.00 16.09 ATOM 454 0 VAL 51 1.329 19.637 36.890 1.00 17.31 ATOM 455 N HIS 52 0.755 20.857 38.688 1.00 17.95 ATOM 456 H HIS 52 0.631 20.876 39.664 1.00 0.00 ATOM 457 CA HIS 52 0.417 22.050 37.930 1.00 19.66 ATOM 458 CB HIS 52 -0.950 21.947 37.264 1.00 21.46 ATOM 459 CG HIS 52 -1.278 23.126 36.400 1.00 25.94 84 ATOM 460 CD2 HIS 52 -2.324 23.985 36.417 1.00 26.46 ATOM 461 ND1 HIS 52 -0.447 23.555 35.385 1.00 27.09 ATOM 462 HD1 HIS 52 0.379 23.112 35.092 1.00 0.00 ATOM 463 CEl HIS 52 -0.965 24.630 34.818 1.00 24.62 ATOM 464 NE2 HIS 52 -2.105 24.911 35.426 1.00 27.73 ATOM 465 HE2 HIS 52 -2.713 25.644 35.178 1.00 0.00 ATOM 466 c HIS 52 0.429 23.217 38.899 1.00 21.92 ATOM 467 0 HIS 52 -0.241 23.176 39.926 1.00 20.84 ATOM 468 N ASP 53 1.245 24.221 38.592 1.00 26.19 ATOM 469 H ASP 53 1.857 24.140 37.845 1.00 0.00 ATOM 470 CA ASP 53 1.374 25.421 39.415 1.00 26.69 ATOM 471 CB ASP 53 0.043 26.185 39.499 1.00 30.60 ATOM 472 CG ASP 53 -0.369 26.803 38.176 1.00 37.06 ATOM 473 ODi ASP 53 0.465 26.855 37.246 1.00 41.34 ATOM 474 0D2 ASP 53 -1.537 27.243 38.070 1.00 39.93 ATOM 475 C ASP 53 1.859 25.075 40.811 1.00 25.96 ATOM 476 0 ASP 53 1.337 25.589 41.802 1.00 27.13 ATOM 477 N VAL 54 2.844 24.181 40.876 1.00 24.42 ATOM 478 H VAL 54 3.192 23.818 40.037 1.00 0.00 ATOM 479 CA VAL 54 3.441 23.735 42.136 1.00 25.36 ATOM 480 CB VAL 54 4.218 24.896 42.834 1.00 25.58 **.ATOM 481 CG1 VAL 54 5.100 24.360 43.949 1.00 27.09 ATOM 482 CG2 VAL 54 5.077 25.639 41.816 1.00 30.24 ATOM 483 C VAL 54 2.395 23.130 43 .083 1.00 24.41 ATOM 484 0 VAL 54 2.551 23.140 44.310 1.00 24.03 a...ATOM 485 N ARG 55 1.338 22.576 42.500 1.00 22.42 ATOM 486 H ARG 55 1.250 22.563 41.527 1.00 0.00 ATOM 487 CA ARG 55 0.273 21.957 43.272 1.00 23.20 ATOM 488 CB ARG 55 -0.956 22.865 43.334 1.00 28.27 ATOM 489 CG ARG 55 -0.807 23.981 44.356 1.00 39.63 ATOM 490 CD ARG 55 -2.051 24.848 44.467 1.00 48.23 ATOM 491 NE ARG 55 -1.954 25.777 45.595 1.00 56.45 ATOM 492 HE ARG 55 -2.462 25.560 46.404 1.00 0.00 ATOM 493 CZ ARG 55 -1.222 26.891 45.602 1.00 60.28 ATOM 494 NH1 ARG 55 -0.509 27.240 44.535 1.00 63.46 ATOM 495 HH1l ARG 55 -0.514 26.661 43.716 1.00 0.00 ATOM 496 HH12 ARC 55 0.028 28.083 44.550 1.00 0.00 ATOM 497 NH2 ARG 55 -1.192 27.657 46.686 1.00 60.77 ATOM 498 HH21 ARG 55 -1.725 27.400 47.491 1.00 0.00 85 ATOM 499 HH22 ARG 55 -0.647 28.494 46.685 1.00 0.00 9 ATOM 500 ATOM 501 ATOM 502 ATOM 503 ATOM 504 ATOM 505 ATOM 506 ATOM 507 ATOM 508 ATOM 509 ATOM 510 ATOM 511 ATOM 512 ATOM 513 ATOM 514 ATOM 515 ATOM 516 ATOM 517 ATOM 518 ATOM 519 ATOM 520 ATOM 521 ATOM 522 ATOM 523 ATOM 524 ATOM 525 ATOM 526 ATOM 527 ATOM 528 ATOM 529 ATOM 530 ATOM 531 ATOM 532 ATOM 533 ATOM 534 ATOM 535 ATOM 536 ATOM 537 C ARG O ARG N PHE H PHE CA PHE CB PHE CG PHE CD1 PHE CD2 PHE CE1 PHE CE2 PHE CZ PHE C PHE O PHE N HIS H HIS CA HIS CB HIS CG HIS CD2 HIS ND1 HIS -0.084 0.024 -0.499 -0.588 -0.854 -0.498 0.950 1.371 1.897 2.714 3.245 3.654 -2.320 -3.192 -2.586 -1.838 -3.942 -4.248 -4.144 -3.097 -5.198 -6.107 -4.802 -3.532 -2.966 -4.014 -3.099 -5.058 -5.780 -5.217 -5.063 -3.765 -3.449 -2.591 -2.468 -1.609 -2.102 -1.588 20.600 20.377 19.692 19.942 18.341 17.347 17.344 17.844 16.847 17.852 16.850 17.353 18.183 18.802 17.340 16.904 17.049 17.741 19.235 20.066 20.041 19.754 21.303 21.344 22.151 15.533 14.901 14.944 15.455 13.499 12.945 13.316 14.312 12.636 11.854 13.197 14.217 14.836 42.694 41.488 43.567 44.514 43.164 44.270 44.634 45.862 43.749 46.203 44.079 45.310 42.824 43.439 41.838 41.364 41.412 40.080 40.145 39.924 40.523 40.750 40.536 40.178 40.144 41.294 40.765 41.867 42.288 41.848 43.266 43.913 44.772 43.667 43.085 44.349 45.024 45.576 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 18.98 18.12 17.36 0.00 15.57 14.98 12.04 11.96 13.48 13.52 12.78 14.92 14.57 16.84 12.74 0.00 13.90 17.35 22.06 21.97 23.17 0.00 23.20 22.64 0.00 11.98 11.55 10.33 0.00 8.93 5.64 8.00 5.61 6.85 0.00 6.57 6.83 0.00 HD1 CE1 NE2 HE2

C

O

N

H

CA

CB

CG

CD2 ND1 HD1 CE1 NE2 HE2

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

86 ATOM 538 c HIS 58 ATM 58 C I 8 -6.570 13.158 41.267 1.00 9.13 ATOM 539 ATOM 540 ATOM 541 ATOM 542 ATOM 543 ATOM 544 ATOM 545 ATOM 546 1 0 ATOM 547 ATOM 548 ATOM 549 ATOM 550 ATOM 551 1 5 ATOM 552 ATOM 553 ATOM 554 ATOM 555 ATOM 556 ATOM 557 ATOM 558 ATOM 559 ATOM 560 ATOM 561 ATOM 562 ATOM 563 ATOM 564 ATOM 565 ATOM 566 ATOM 567 ATOM 568 ATOM 569 ATOM 570 ATOM 571 ATOM 572 ATOM 573 ATOM 574 ATOM 575 ATOM 576 O HIS N PHE H PHE CA PHE CB PHE CG PHE CD1 PHE CD2 PHE CEl PHE CE2 PHE CZ PHE C PHE O PHE N PRO CD PRO CA PRO CB PRO CG PRO C PRO O PRO N ILE H ILE CA ILE CB ILE CG2 ILE CG1 ILE CD ILE C ILE O ILE N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU 58 59 59 59 59 59 59 59 59 59 59 59 59 60 60 60 60 60 60 60 61 61 61 61 61 61 61 61 61 62 62 62 62 62 62 62 62 .62 -7 .603 -6.551 -5 .709 -7.769 -7.703 -7.623 -6 .397 -8 .777 -6.318 -8.713 -7.481 -8.021 -7.232 -9.108 -10.034 -9 .374 -10.420 -11.125 -9.881 -10.659 -9.355 -8.723 -9.724 -8.472 -8.868 -7 .655 -6.296 -10 .497 -9 .978 -11.739 -12.099 -12 .582 -13.981 -14.906 -16.305 -16.458 -17.251 -12.688 13.507 41.831 12.519 40.107 12.287 39.679 12.150 39.408 12.621 37.948 14.109 37.789 14.762 37.851 14.861 37.599 16.146 37.731 16.248 37.478 16.893 37.544 10.650 39.427 9.868 38.893 10.220 40.075 10.958 40.953 8 .782 40.094 8.640 41.206 9.952 41.195 8.310 38.719 9.000 38.051 7.180 38.267 6.742 38.838 6 .582 36.986 6.222 36.164 5.536 34.856 7 .482 35.886 7.211 35.307 5.309 37.308 4.413 37.984 5 .240 36.845 5.968 36.290 4.084 37.112 4.541 37.538 3.407 37.975 3 .882 38.332 4.548 39.381 3.579 37.569 3.162 35.910 1.00 12.23 1.00 9.57 1.00 0.00 1.00 12.32 1.00 11.96 1.00 13.50 1.00 12.51 1.00 13 .89 1.00 17.22 1.00 17.22 1.00 17.16 1.00 13.06 .00 12.71 1.00 14.37 .00 13.14 1.00 15.39 1.00 15.06 1.00 16.60 1.00 15.44 1.00 16.09 1.00 15.98 1.00 0.00 1.00 15.23 1.00 14.68 1.00 15.39 1.00 13.45 1.00 12.44 1.00 17.07 1.00 16.51 1.00 19.22 1.00 0.00 1.00 23.18 1.00 30.15 1.00 39.45 1.00 44.10 1.00 48.25 1.00 44.87 1.00 23.10 87 ATOM 577 0 GLU 62 -12.709 3.619 34.766 1.00 21.60 ATOM 578 ATOM 579 ATOM 580 ATOM 581 ATOM 582 ATOM 583 ATOM 584 ATOM 585 ATOM 586 ATOM 587 ATOM 588 ATOM 589 ATOM 590 15 ATOM 591 ATOM 592 ATOM 593 ATOM 594 ATOM 595 ATOM 596 ATOM 597 ATOM 598 ATOM 599 ATOM 600 25 ATOM 601 ATOM 602 ATOM 603 ATOM 604 ATOM 605 ATOM 606 ATOM 607 ATOM 608 ATOM 609 ATOM 610 ATOM 611 ATOM 612 ATOM 613 ATOM 614 ATOM 615 N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NH1 ARG HH11 ARG HH12 ARG NH2 ARG HH21 ARG HH22 ARG C ARG O ARG N GLN H GLN CA GLN CB GLN CG GLN CD GLN OE1 GLN NE2 GLN HE21 GLN HE22 GLN C GLN O GLN N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU -12.721 -12.684 -12.848 -12.152 -12.177 -11.909 -12.927 -13.820 -12.730 -11.546 -10.792 -11.407 -13.714 -14.605 -13.559 -14.332 -15.002 -14.851 -14.266 -16.257 -16.672 -17.287 -16.263 -16.145 -15.511 -15.640 -14.861 -16.545 -15.648 -17.816 -18.450 -18.268 -19.792 -20.691 -22.145 -20.501 -17.849 -17.547 1.862 1.558 0.861 -0.437 -1.521 -2.885 -3.223 -2.825 -4.030 -4.600 -4.431 -5.204 -4 .247 -3 .810 -4.855 0.590 0.123 0.931 1.330 0.706 1.454 2.819 3 .870 4.290 4.307 3.928 4.992 -0.778 -1.570 -1.133 -0.436 -2.510 -2.583 -1.926 -2.279 -0.410 -3.137 -4.327 36.180 37.114 35.135 35.547 34.477 35.079 36.072 35.972 37.111 37.306 36.671 38.089 37.975 37. 847 38.754 34.944 35.867 33.771 33.103 33.464 32.196 32.432 32.775 33.929 31.774 30.878 32.008 33.279 32.982 33.412 33.661 33.264 33.418 32.359 32.653 32.318 31.934 31.873 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 24.50 0.00 28.70 31.42 36.91 40.57 46.47 0.00 47.98 48.36 0.00 0.00 47.23 0.00 0.00 28.52 29.96 29.71 0.00 33 .43 36.64 39.67 40.97 42.60 41.46 0.00 0.00 35.62 35.48 38.38 0.00 42.81 47.54 51.72 54.58 51.28 43.23 44.38 88 ATOM 616 N ASN 66 -17.801 -2.329 30.879 1.00 42.92

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

617 H ASN 618 CA ASN 619 CB ASN 620 CG ASN 621 OD1 ASN 622 ND2 ASN 623 HD21 ASN 624 HD22 ASN 625 C ASN 626 O ASN 627 N GLY 628 H GLY 629 CA GLY 630 C GLY 631 O GLY 632 N THR 633 H THR 634 CA THR 635 CB THR 636 OG1 THR 637 HG1 THR 638 CG2 THR 639 C THR 640 O THR 641 N TYR 642 H TYR 643 CA TYR 644 CB TYR 645 CG TYR 646 CD1 TYR 647 CE1 TYR 648 CD2 TYR 649 CE2 TYR 650 CZ TYR 651 OH TYR 652 HH. TYR 653 C TYR 654 O TYR -18.004 -17.421 -18.052 -17.404 -16.998 -17.292 -17.611 -16.904 -15.909 -15.444 -15.144 -15.525 -13.700 -12.924 -11.718 -13.594 -14.552 -12.897 -13.738 -14.997 -15.528 -13.962 -12.536 -12.941 -11.769 -11.499 -11.345 -9.845 -9.452 -9.286 -8.936 -9.256 -8.905 -8.745 -8.389 -8.332 -11.646 -11.509 -1.382 -2.825 -1.973 -0.612 -0.009 -0.124 -0.677 0.765 -2.916 -3.072 -2.788 -2.652 -2.884 -1.642 -1.728 -0.501 -0.492 0.732 1.639 1.940 1.140 0.970 1.480 1.075 2.558 2.867 3.355 3.184 1.783 0.801 -0.501 1.433 0.138 -0.824 -2.102 -2.618 4.818 5.296 30.987 29.559 28.456 28.327 29.321 27.100 26.357 26.986 29.346 28.215 30.425 31.316 30.321 29.927 29.706 29.801 29.964 29.450 28.531 29.149 29.220 27.186 30.731 31.821 30.600 29.726 31.744 31.984 32.360 31.386 31.731 33.693 34.050 33.065 33.417 32.605 31.489 30.360 1.00 0.00 1.00 42.31 1.00 45.73 1.00 48.82 1.00 52.33 1.00 52.00 1.00 0.00 1.00 0.00 1.00 41.37 1.00 42.54 1.00 39.06 1.00 0.00 1.00 35.20 1.00 31.27 1.00 32.16 1.00 28.74 1.00 0.00 1.00 26.00 1.00 26.73 1.00 28.49 1.00 0.00 1.00 27.12 1.00 24.27 1.00 23.18 1.00 22.13 1.00 0.00 1.00 20.20 1.00 17.55 1.00 15.74 1.00 16.67 1.00 18.61 1.00 15.77 1.00 17.24 1.00 18.54 1.00 19.33 1.00 0.00 1.00 20.07 1.00 19.19 89 p p 15 ATOM 655 ATOM 656 ATOM 657 ATOM 658 ATOM 659 ATOM 660 ATOM 661 ATOM 662 ATOM 663 ATOM 664 ATOM 665 ATOM 666 ATOM 667 ATOM 668 ATOM 669 ATOM 670 ATOM 671 ATOM 672 ATOM 673 ATOM 674' ATOM 675 ATOM 676 ATOM 677 ATOM 678 ATOM 679 ATOM 680 ATOM 681 ATOM 682 ATOM 683

N

H

CA

CB

C

0

N

H

CA

CB

CG2 CG1

CD

C

O

N

H

CA

CB

C

O

N

H

CA

C

0

N

H

CA

C

O

N

H

CA

CB

CG

CD

CE

NZ

ALA

ALA

ALA

ALA

ALA

ALA

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ALA

ALA

ALA

ALA

ALA

ALA

GLY

GLY

GLY

GLY

GLY

GLY

GLY

GLY

GLY

GLY

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

-12.038 -12.144 -12.346 -13.703 -12.333 -12.569 -11.975 -11.708 -11.982 -11.079 -11.206 -9.623 -8.669 -13.445 -14.057 -14.016 -13.481 -15.417 -15.759 -15.764 -15.242 -16.628 -16.960 -17.044 -16.171 -16.375 -15.201 -15.099 -14.320 -14.561 -15.276 -13.954 -13.391 -14.112 -13.575 -14.604 -13.992 -13.261 -12.808 5.538 5.122 6.951 7.123 7.727 7.169 9.001 9.364 9.909 11.134 12.132 10.691 11.832 10.346 10.481 10.525 10.391 10.922 11.228 12.113 13.212 11.874 10.963 12.932 13.105 14.032 12.215 11.459 12.301 11.132 10.191 11.178 11.953 10.109 10.550 11.333 12.101 13.349 14.218 32.534 33.421 32.380 31.701 33.683 34.760 33.573 32.704 34.704 34.450 35.593 34.285 34.009 34.719 33.659 35.904 36.712 36.026 37.480 35.138 35.324 34.158 34.030 33.254 32.025 31.239 31.852 32.459 30.706 29.782 30.131 28.604 28.407 27.630 26.266 25.454 24.290 24.773 23.647 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 20.74 0.00 22.43 20.46 23.77 23.69 24.06 0.00 24.49 23.76 23.11 22.21 18.51 26.14 23.83 29.31 0.00 33.39 33.93 34.98 34.89 36.34 0.00 36.52 35.63 37.15 33.13 0.00 32.37 34.04 34.17 34.83 0.00 35.85 40.25 48.14 53.33 57.38 59.74

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

684 685 686 687 688 689 690 691 692 693 90 ATOM 694 HZ1 LYS 75 -13.632 14.560 23.114 1.00 0.00 15

A

A

A

A

25A

A

A

A

A

A

A

A

A

ATOM 695 ATOM 696 ATOM 697 ATOM 698 ATOM 699 ATOM 700 ATOM 701 ATOM 702 ATOM 703 ATOM 704 ATOM 705 ATOM 706 A.TOM 707 WTOM '708 %TOM 709 kTOM 710 ~TOM 711 TOM 712 TOM 713 TOM 714 ~TOM 715 ~TOM 716 TOM 717 ~TOM 718 TOM 7 19 TOM 720 TOM 721 TOM 7 22 TOM 723 TOM 724 TOM 725 TOM 726 TOM 727 TOM 728 TOM 729 TOM 730 TOM 7-11 TOM 732

N

H

CA

CB

CG

CD2 ND1 HD1 CEl NE2 HE2

C

0

N

H

CA

CB

SG

C

0

N

H

CA

C

0

N

CD

CA

HZ2 LYS HZ3 LYS C LYS 0 LYS N ALA H ALA CA ALA CB ALA C ALA 3 ALA

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

CYS

CYS

CYS

CYS

CYS

CYS

CYS

GLY

GLY

GLY

GLY

GLY

PRO

PRO

PRO

75 75 75 75 76 76 76 76 76 76 77 77 77 77 77 77 77 77 77 77 77 77 77 78 78 78 78 78 78 78 79 79 79 79 79 80 80 80 -12.192 -12.282 -13 .461 -12.416 -14.114 -14.954 -13.606 -14.719 -12.479 -12.464 -11.525 -11. 587 -10.389 -9.130 -9.230 -8.946 -9.699 -10.027 -9.699 -9 .248 -9.158 -10.236 -10. 611 -9.703 -9.406 -9.542 -9.278 -8.119 -8.489 -8.370 -7.733 -7.837 -6.714 -6.019 -6.128 -5.281 -5.090 -4.559 13 .677 15.027 8.807 8.812 7.695 7.758 6.380 5.342 6.005 6.419 5.237 4.898 4.800 5.559 7.040 7.826 7.888 7. 624 9 .130 9.118 9.891 3.302 2.786 2.599 3 .050 1.153 0.566 1.534 0.668 -0.530 1.590 2 .542 1.202 2.397 3 .513 2 .194 0.904 3 .264 23 .006 24.027 28.082 28.741 27.767 27.270 28.126 28.061 27.179 26.022 27.683 28.592 26.893 27.313 27 .123 26 .057 28.105 28.994 27.652 26.412 25.818 27.118 28.169 26 .128 25.306 26.224 24 .841 23.883 27.211 27.443 27.797 27.613 28.754 29.371 28.854 30.473 31.157 31.165 i. 00 0.00 1.00 0.00 1.00 34.24 1.00 33.16 .00 31.87 1.00 0.00 1.00 31.22 .00 30.23 1.00 28.77 1.00 30.26 1.00 27.21 i. 00 0.00 1 .00 27.71 1.00 27.15 1.00 28.63 1.00 27.68 1.00 29.85 1.00 0.00 1.00 28.48 1.00 29.23 1.00 0.00 1.00 28.88 1.00 27.46 1.00 29.61 i. 00 0.00 1.00 30.03 1.00 34.14 1.00 44.93 1.00 25.84 1.00 26.98 1.00 23.67 1.00 0.00 1.00 18.52 1.00 18.97 1.00 18.14 1.00 18.06 1.00 18.29 1.00 17.93 91 9O

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

733 734 735 736 737 738 739 740 741 742 743 744 745 746 747 748 749 750 751 752 753 754 755 756 757 758 759 760 761 762 763 764 765 766 767 768 769 770 771 N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU 0 GLU N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N CYS H CYS CA CYS CB CYS SG CYS C CYS O CYS N GLU

GLU

CA GLU

PRO

PRO

PRO

PRO

ALA

ALA

ALA

ALA

ALA

ALA

-3.931 -3.791 -3 .510 -3 .408 -2.757 -2 .864 -1.742 -0.945 -2.367 -1.862 -3.481 -3.847 -4.188 -5.298 -4.808 -4.489 -4.351 -4.382 -4.780 -4.855 -5.199 -5.136 -5.769 -6.359 -6.973 -8.124 -5.907 694 -4.927 -3.506 -3.372 -2.412 -1.265 -1.663 -1.925 -1.586 -1.911 -2.190 -1.486 2.536 1.121 3.963 5.190 3 .192 2.214 3 .776 2.682 4.713 5.810 4.284 3.436 5 .066 4.238 3 .159 1 .824 0.817 1.763 6.333 7.368 6.244 5.386 7 .383 6.929 7.966 7.338 8.526 8 .454 9 .632 8.039 7 .082 8 .979 8 .308 7 .902 9 .578 10.761 8.766 7.833 9.218 32.357 31. 873 30.289 30.300 29.510 29.533 28.635 27.941 27.600 27.363 27.009 27.305 25.994 25.334 24.372 25 .043 24. 317 26.284 26.591 25.928 27.846 28.316 28.548 29.888 30.825 31. 597 31. 766 28.742 28.462 29 .167 29.354 29.377 30.129 31. 846 28.060 27.999 27.005 27.119 25.680 1.00 20.63 1.00 19.63 1.00 17.24 1.00 14.92 1.00 15.32 1.00 0.00 1.00 15.99 1.00 15.92 1.00 16.17 1.00 15.48 1.00 18.46 1.00 0.00 1.00 18.23 1.00 20.10 1.00 25.98 1.00 30.34 1.00 35.16 1.00 30.98 1.00 17.53 1.00 15.66 1.00 16.88 1.00 0.00 1.00 17.11 1.00 17.19 1.00 16.72 1.00 16.47 1.00 15.85 1.00 17.05 1.00 17.29 1.00 16.35 1.00 0.00 1.00 17.56 1.00 16.45 1.00 14.67 1.00 20.60 1.00 20.51 1.00 22.93 1.00 0.00 1.00 23.75 92

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

772 773 774 775 776 777 778 779 780 781 782 783 784 785 786 787 788 789 790 791 792 793 794 795 796 797 798 799 800 801 802 803 804 805 806 807 808 809 810 CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU O GLU N PHE H PHE CA PE CB PHE CG PHE CD1 PE CD2 PHE CEl PE CE2 PE CZ PE C PE o PE N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CEl TYR CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR C TYR O T YR N SER H SER CA SER CB SER OG SER HG S ER 85 85 85 85 85 85 85 86 86 86 86 86 86 86 86 86 86 86 86 87 87 87 87 87 87 87 87 87 87 87 87 87 87 88 88 88 88 88 88 -1.420 -0.364 -0.285 -1.165 0.681 -2.439 -2.002 -3.735 -4.026 -4.758 -6.158 -7.265 -7.693 -7.874 -8 .713 -8.892 -9.314 609 -4 .657 -4.438 -4.421 -4.291 -4.562 -6.021 -6.455 -7.798 970 -8.320 -8.727 -10.052 -10.057 -2.967 -2 .795 -2.026 -2.190 -0.737 0.268 0.565 -0.251 8.034 6.990 5.806 4.919 5.751 10. 298 11. 304 10.109 9.296 11. 063 10.499 11. 504 11.867 12.093 12.803 13 .029 13.385 12.408 13.457 12.378 11.516 13 .604 13.340 13 .088 11.844 11. 603 14.099 13 .873 12.618 12 .356 11.542 14.337 15.458 13 .691 12.769 14.305 13.249 12.303 11.986 24.703 25 .079 24.115 24.169 23 .319 25 .164 24.602 25 .404 25.868 24.981 25.245 25.064 23.795 26.169 23 .628 26.015 24.742 25.679 25 .032 26.998 27.464 27.776 29.250 29.531 29.967 30.242 29.371 29.644 30.081 30.364 30.886 27 .578 28.061 26.895 26.608 26.584 26.112 27 .124 27 .522 1.00 27.58 1.00 36.56 1.00 40.46 1.00 38.44 1.00 46.15 1.00 23.52 1.00 23.99 1.00 23.07 1.00 0.00 1.00 22.06 1.00 23.30 1.00 25.88 1.00 28.15 1.00 27.77 1.00 30.93 1.00 27.23 1.00 30.08 1.00 22.18 1.00 22.09 1.00 20.74 1.00 0.00 1.00 20.26 1.00 1 .00 1 .00 1 .00 1 .00 1 .00 1.00 1.00 1 .00 1.00 1.00 1.00 1 .00 1 .00 1.00 1.00 1 .00 17 19 .72 20.21 25.37 19 .83 21.99 25.65 25.64 0 .00 20.79 20.79 24.94 0.00 28.11 27.90 35.96 0 .00 93 ATOM 811 C SER 88 -0.989 15.288 25.443 1.00 29.72 ATOM 812 0 SER 88 -0.360 16.344 25.361 1.00 30.51 ATOM 813 N ARG 89 -1.917 14.924 24.563 1.00 31.17 ATOM 814 H ARG 89 -2.399 14.082 24.692 1.00 0.00 ATOM 815 CA ARG 89 -2.265 15.750 23.418 1.00 35.74 ATOM 816 CB ARG 89 -2.712 14.874 22.243 1.00 40.10 ATOM 817 CG ARG 89 -1.582 14.360 21.356 1.00 47.31 ATOM 818 CD ARG 89 -0.637 13.443 22.108 1.00 51.57 ATOM 819 NE ARG 89 0.489 13.018 21.281 1.00 54.95 1 0 ATOM 820 HE ARG 89 0.313 12.782 20.344 1.00 0.00 ATOM 821 CZ ARG 89 1.742 12.918 21.719 1.00 56.98 ATOM 822 NH1 ARG 89 2.039 13.215 22.980 1.00 56.68 ATOM 823 HH11 ARG 89 1.325 13.519 23.611 1.00 0.00 ATOM 824 HH12 ARG 89 2.982 13.141 23.303 1.00 0.00 5 ATOM 825 NH2 ARG 89 2.700 12.511 20.897 1.00 57.57 :.*ATOM 826 HH21 ARG 89 2.477 12.279 19.950 1.00 0.00 :::ATOM 827 HH2 2 ARG 89 3.642 12.430 21.228 1.00 0.00 ATOM 828 c ARG 89 -3.352 16.762 23.734 1.00 35.85 ATOM 829 o ARG 89 -3.263 17.924 23.334 1.00 36.15 ATOM 830 N ASP 90 -4.375 16.327 24.457 1.00 37.16 ATOM 831 H ASP 90 -4.418 15.403 24.786 1.00 0.00 *ATOM 832 CA ASP 90 -5.484 17.206 24.793 1.00 38.14 9.ATOM 833 CB ASP 90 -6.696 16.820 23.935 1.00 41.72 ATOM 834 CG ASP 90 -7.849 17.796 24.064 1.00 45.64 25 ATOM 83 5 ODi ASP 90 -9.005 17.364 23.872 1.00 49.81 ATOM 836 0D2 ASP 90 -7.608 18.992 24.342 1.00 47.83 ATOM 837 c ASP 90 -5.841 17.147 26.278 1.00 35.95 ATOM 838 0 ASP 90 -6.216 16.094 26.786 1.00 35.57 ATOM 839 N PRO 91 -5.724 18.285 26.992 1.00 35.06 ATOM 840 CD PRO 91 -5.220 19.578 26.497 1.00 34.31 ATOM 841 CA PRO 91 -6.040 18.368 28.424 1.00 34.83 ATOM 842 C B PRO 91 -5.934 19.865 28.705 1.00 33 .84 ATOM 843 CG PRO 91 -4.858 20.296 27.778 1.00 35.60 ATOM 844 c PRO 91 -7.453 17.855 28.705 1.00 34.95 ATOM 845 0 PRO 91 -7.685 17.165 29.695 1.00 34.91 ATOM 846 N ASP 92 -8.393 18.245 27.844 1.00 34.68 ATOM 847 H ASP 92 -8.121 18.822 27.107 1.00 0.00 ATOM 848 CA ASP 92 -9.796 17.837 27.934 1.00 34.83 ATOM 849 CB ASP 92 -9.980 16.465 27.261 1.00 38.56 94 0*S* 0* 0* C e.g.

S

9* C. C

OSS*

0* 0 5

C.

C

S

6*@O

S

*OC@

C

@OOC

e.g.

0O 5O 0

C

OOSS

0 0 0 C 500 CS

C

1 5 20 ATOM 850 ATOM 851 ATOM 852 ATOM 853 ATOM 854 ATOM 855 ATOM 856 ATOM 857 ATOM 858 ATOM 859 ATOM 860 ATOM 861 ATOM 862 ATOM 863 ATOM 864 ATOM 865 ATOM 866 ATOM 867 ATOM 868 ATOM 869 ATOM 870 ATOM 871 ATOM 872 ATOM 873 ATOM 874 ATOM 875 ATOM 876 ATOM 877 ATOM 878 ATOM 879 ATOM 880 ATOM 881 ATOM 882 ATOM 883 ATOM 884 ATOM 885 ATOM 886 ATOM 887 CG ASP ODi ASP 0D2 ASP C ASP O ASP N GLY

H

CA

CB

CG

CD1 CD2

C

0

GLY

GLY

GLY

GLY

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

PRO

PRO

PRO

PRO

PRO

PRO

-11.441 16.132 -11.864 14.990 -12.165 17.008 -10.380 17.841 -11.021 16.879 -10.165 18.939 -9.648 19.684 -10.691 19.042 -9.647 19.125 -9.932 19.620 -8.456 18.600 -8.292 18.164 -7.380 18.642 -6.266 17.654 -6.578 16.165 -5.314 15.463 -7.097 15.552 -6.813 20.064 -6.956 20.826 -6.160 20.439 -5.991 19.647 -5.571 21.774 -5.025 21.736 -4.772 20.274 -4.475 22.088 -4.074 23.245 -3.953 21.041 -4.241 20.128 -2.917 21.145 -1.596 21.666 -0.775 20.589 -2.721 19.754 -3.133 18.762 -2.137 19.678 -1.807 20.482 -1.903 18.386 -1.602 18.556 -0.321 19.321 -0.142 20.430 26.973 27.264 26. 452 29.358 29.789 30. 078 29.719 31.428 32.523 33.614 32.262 31.399 33.244 32.867 32.692 32.246 33.978 33.290 32.329 34.407 35.637 34.568 35.999 36.244 33.544 33 .386 32.912 33 .129 31. 884 32.467 33.668 31. 295 31.899 30.106 29.650 29.473 27 .980 27.727 28.230 1.00 43.08 1.00 46.42 1.00 46.09 1.00 33.28 1.00 32.13 1.00 32.19 1.00 0.00 1.00 30.80 1.00 28.16 1.00 29.26 1.00 25.58 1.00 0.00 1.00 25.19 1.00 23.59 1.00 21.25 1.00 20.19 1.00 20.15 1.00 27.14 1.00 26.74 1.00 27.36 1.00 27.79 1.00 27.68 1.00 28.71 1.00 28.16 1.00 27.92 1.00 28.39 1.00 28.28 1.00 0.00 1.00 27.50 1.00 27.76 1.00 30.21 1.00 27.05 1.00 28.24 1.00 24.88 1.00 0.00 1.00 24.53 1.00 26.26 1.00 27.29 1.00 33.19 25 o PRO N CYS H CYS CA CYS CB CYS SG CYS C CYS 0 CYS N ASN H ASN CA ASN CB ASN CG ASN ATOM 888 ODi ASN 97 95 ATOM 889 ND2 ASN 97

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

890 891 892 893 894 895 896 897 898 899 900 901 902 903 904 905 906 907 908 909 910 911 912 913 914 915 916 917 918 919 920 921 922 923 924 925 926 927 HD2 1 HDl22

C

0

N

H

CA

CB

CG

CD1 CD2

C

0

N

H

CA

CB

CG

CD

NE

HE

C z NH1 HH11 HH12 NH2 HH2 1 HF122

C

0

N

H

CA

CB

CG

CD

C E

NZ

ASN

ASN

ASN

ASN

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

97 97 97 97 98 98 98 98 98 98 98 98 98 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99 100 100 100 100 100 100 100 100 0.577 18.737 26.950 1.00 29.41 0.365 17.861 26.558 1.00 0.00 1.409 19.221 26.806 1.00 0.00 -0.746 17.667 30.165 1.00 23.01 0.075 18.291 30.847 1.00 21.65 -0.691 16.353 29.992 1.00 21.64 -1.373 15.929 29.433 1.00 0.00 0.359 15.546 30.594 1.00 21.20 -0.034 14.069 30.570 1.00 17.06 -1.357 13.699 31.251 1.00 16.71 -1.549 12.185 31.223 1.00 12.58 -1.370 14.216 32.684 1.00 14.60 1.684 15.754 29.867 1.00 23.86 1.835 15.360 28.708 1.00 26.15 2.630 16.392 30.549 1.00 26.16 2.455 16.653 31.475 1.00 0.00 3.951 16.674 29.994 1.00 28.30 4.241 18.177 30.025 1.00 26.96 3.171 19.070 29.447 1.00 30.41 3.508 20.526 29.734 1.00 34.41 2.427 21.433 29.355 1.00 38.66 1.995 21.299 28.487 1.00 0.00 1.982 22.430 30.116 1.00 41.42 2.521 22.659 31.307 1.00 44.31 3.261 22.076 31.642 1.00 0.00 2.176 23.402 31.880 1.00 0.00 0.991 23.199 29.685 1.00 42.74 0.582 23.034 28.788 1.00 0.00 0.656 23.950 30.253 1.00 0.00 5.022 15.981 30.827 1.00 30.19 5.260 16.353 31.973 1.00 35.13 5.682 14.992 30.245 1.00 29.39 5.435 14.728 29.337 1.00 0.00 6.746 14.275 30.935 1.00 27.27 7.818 15.244 31.451 1.00 28.94 9.056 14.548 31.998 1.00 38.33 10.106 15.539 32.483 1.00 43.68 11.359 14.824 32.989 1.00 45.64 11.077 13.949 34.166 1.00 47.84 96

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

928 929 930 931 932 933 934 935 936 937 938 939 940 941 942 943 944 945 946 947 948 949 950 951 952 953

LYS

LYS

PRO

CD PRO CA PRO CB PRO CC PRO C PRO 0 PRO N CYS H CYS CA CY--S CB CILs SG CYZS C CYS O CYS N ASN H ASN CA ASN CB ASN CC ASN 001 ASN ND2 ASN HZ1 LYS HZ2 LYS HZ3 LYS 100 100 100 100 100 101 101 101 101 101 101 101 102 102 102 102 102 102 102 103 103 103 103 103 103 103 103 103 103 103 104 104 104 104 104 104 104 104 104 10.401 10.658 11. 961 6.306 5.879 6.365 6.598 5.985 5.909 6.897 7.058 8.252 6.633 5.688 7.563 6.898 7.994 7.929 7.358 8.853 9.232 9.283 10.196 9.503 8.353 10.196 11.100 9.759 9.966 10.709 9.699 9.110 10.274 9.781 8.431 8.002 7.520 6.667 8.170 13.212 14.516 13.513 13.355 13 .802 12.043 11. 395 11. 063 9.762 9.978 10.992 11.122 10.823 10.683 10.720 11. 178 11. 195 9.245 8.488 8.834 9.505 7.440 7.218 7.509 7 .121 8.205 8 .507 8 .409 6.941 7.676 5. 684 5.152 5.054 3 .610 3.450 1.999 1.576 1.930 0.759 33.886 34.932 34.494 32.070 33.136 31.827 30.525 32.840 32.040 30.934 33.923 33.644 35 .165 35.322 36.268 37.557 38.960 36.344 37 .130 35.485 34.875 35.421 34.212 32 .896 32.679 32.013 32.225 31. 149 36.688 37.341 37.027 36.460 38.207 38.330 38.999 39.007 37.696 37.380 36.874 1.00 0.00 1.00 0.00 1.00 0.00 1.00 23.90 1.00 21.73 1.00 20.62 1.00 19.79 1.00 18.73 1.00 20.97 1.00 22.39 1.00 17.30 1.00 16.81 1.00 15.53 1.00 0.00 1.00 13 .89 1.00 13 .31 1.00 16.63 1.00 14.55 1.00 15.10 1.00 14.85 1.00 0.00 1.00 15.80 1.00 16.28 1.00 15.02 1.00 16.41 1.00 20.99 1.00 0.00 1.00 0.00 1.00 17.75 1.00 17.16 1.00 16.96 1.00 0.00 1.00 19 .38 1.00 19.40 1.00 17.82 1.00 17.65 1.00 26.48 1.00 0.00 1.00 25.18 954 HD21 AS:: 955 HD22 ASN 956 C AS 957 0 ASN 958 N ARC 959 F ARG 960 CA ARC 961 CB ARC 962 CC ARC.

963 CD ARFG 964 NE ARG 965 HE ARG 966 CZ ARC 97 9.

9 9*

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

967 968 969 970 971 972 973 974 975 976 977 978 979 980 981 982 983 984 985 986 987 988 989 990 991 992 993 994 995 996 997 998 999 1000 1002.

1002 1003 1004 1005

PRO

PRO

PRO

PRO

NHl ARG HH11 ARG HH12 ARG NH2 ARG HH21 ARG H{H22 ARG C ARG 0 ARG N PRO 104 104 104 104 104 104 104 104 105 105 105 105 105 105 105 106 106 106 106 106 106 106 106 C PRO 0 PRO N SEFR

SER

SER

SER

SER

SER

SER

SER

9.350 9.760 9.829 7.628 6.735 8.101 11. 796 12.395 12.440 11. 847 13 .902 14.160 12.960 14.429 13 .750 15. 631 16.143 16.241 17.652 17.637 17.148 16.282 16.701 15.808 15.421 15.794 14.462 14.281 13.536 13.708 12.219 11.828 10.439 10.341 10.173 11. 201 11.107 10.463 10.572 0.260 0.484 -0.357 0.429 0.803 -0.194 5.059 4.746 5.453 5.983 5 .487 5.980 6.824 4.070 3 .103 3.946 4.736 2.638 2.810 3 .643 3.214 1.840 2.350 0.601 0.264 -0.239 -0.209 -0.921 0.621 1.194 0.719 2 .184 2 .415 1.718 3 .897 0.036 0.337 -0.908 -1.085 37.213 38.095 36.586 35.712 35.464 35.088 38.163 37.133 39.273 40.512 39.341 40.760 41.053 39.163 39.517 38,613 38.342 38.393 37 .829 36.680 35.971 39.697 40.741 39.636 38.806 40 .817 41.544 42.532 41.071 40.292 41. 683 41.901 42.506 43.849 42 .660 40.786 39.600 41.353 42.309 1.00 29.12 1.00 0.00 1.00 0.00 1.00 30.66 1.00 0.00 1.00 0.00 1.00 23.50 1.00 23.54 1.00 27.13 1.00 29.49 1.00 29.70 1.00 30.41 1.00 31.24 1.00 32.78 1.00 33 1.00 36.54 1.00 0.00 1.00 37.78 1.00 40.86 1.00 45.12 1.00 0.00 1.00 37.20 1.00 37.55 1.00 36.08 1.00 0.00 1.00 35.61 1.00 34.68 1.00 37.59 1.00 31.21 1.00 0.00 1.00 29.48 1.00 31.06 1.00 33.10 1.00 35.40 1.00 34.68 1.00 28.12 1.00 27.81 1.00 27.83 1.00 0.00 9* N GLY 107 H GLY 107 CA GLY 107 C GLY 107 0 GLY 107 N LEU 108 H LEU 108 CA LEU 108 CB LEU 108 CG LEU 108 CD1 LEU 108 CD2 LEU 108 C LEU 108 0 LEU 108 N GLU 109 H GLU 109 98 ATOM 1006 CA GLU 109 ATM 00 C GU 099.448 -1.644 40.612 1.00 26.64

ATOM

ATOM

1007 1008

C

C.

1 5 20 ATOM 1009 ATOM 1010 ATOM 1011 ATOM 1012 ATOM 1013 ATOM 1014 ATOM 1015 ATOM 1016 ATOM 1017 ATOM 1018 ATOM 1019 ATOM 1020 ATOM 1021 ATOM 1022 ATOM 1023 ATOM 1024 ATOM 1025 ATOM 1026 ATOM 1027 ATOM 1028 ATOM 10291 ATOM 1030 ATOM 1031 ATOM 1032 ATOM 1033 ATOM 1034 ATOM 1035 ATOM 1036 ATOM 1037 ATOM 1038 ATOM 1039 ATOM 1040 ATOM 1041 ATOM 1042 ATOM 1043 ATOM 1044 CE GLU 109 CG GLU 109 CD GLU 109 OE1 GLU 109 0E2 GLU 109 C GLU 109 O GLU 109 N PRO 110 CD PRO 110 CA PRO 110 CB PRO 110 CG PRO 110 C PRO 110 O PRO 110 N GLN 111 H GLN 111 CA GLN i11 CB GLN i1l CG GLN i11 CD GLN 111 OE1 GLN i11 NE2 GLN i11 HE22 GLN 111 C GLN 111 O GLN il1 N PRO 112 CD PRO 112 CA PRO 112 CB PRO 112 CC PRO 112 C PRO 112 O PRO 112 N GLY 113 H GLY 113 CA GLY 113 C GLY 113 O GLY 113 9.663 11.066 11.373 11. 182 11. 821 8.080 7.989 7.002 6.918 5 .678 4.753 5.496 5.337 5.600 4.803 4.634 4.447 4.206 3 .892 5.096 6.224 4.863 3.934 5.625 3.220 2.161 3.356 4.563 2 .207 2.831 3.981 1.162 1.510 -0.110 -0.338 -1.184 -1.504 -1.523 -3 .151 -3 .653 -3 .558 -4.568 -2.485 -1.236 -0.648 -1.480 -1.981 -1.103 -1.406 -2.439 -1.920 -3 .119 -1 .245 -0.287 869 -0.774 -1.263 852 -1.390 -2.881 -3 .187 -3 .267 -2 .778 -2.358 -4.052 -4 .760 -4.961 -6.322 -5.966 -4.553 -4.094 -4 .671 -5.036 -4.317 -5.450 -6.625 40.801 40.433 38.940 38.228 38.479 41.156 42.241 40.389 39.007 40.896 39.715 38.930 42 .144 42.202 43 .155 43 .041 44.425 45.469 46.873 47 .581 47 .404 48.389 48 .464 48.862 44.329 43 .856 44.738 45.201 44.676 44.999 45.896 45.716 46.810 45.348 44.467 46.256 47 .212 46.827 1.00 33.21 1.00 42.25 1.00 48.40 1.00 52.92 1.00 51.82 1.00 23.58 1.00 23.49 1.00 19.24 1.00 16.22 1.00 16.34 1.00 14.78 1.00 18.83 1.00 16.63 1.00 16.68 1.00 16.60 1.00 0.00 1.00 16.91 1.00 21.09 1.00 29.38 1.00 35.11 1.00 39.80 1.00 39.14 1.00 0.00 1.00 0.00 1.00 15.31 1.00 12.08 1.00 16.34 1.00 15.65 1.00 16.29 1.00 17.56 1.00 18.96 1.00 13.47 1.00 12.01 1.00 14.46 1.00 0.00 1.00 14.99 1.00 15.75 1.00 15.37 99 ATOM 1045 N VAL 114 ATOM 2.05 N VAL 114 -1.735 -5.107 48.471 1.00 13.61

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1046 1047 1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 1061 1062 1063 1064 1065 1066 1067 1068 1069 1070 1.071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 H VAL 114 CA VAL 114 CS VAL 114 CG1 VAL 114 CG2 VAL 114 C VAL 114 O VAL 114 N PHE 115 H PHE 115 CA PHE 115 CB PHE 115 CG PHE 115 CD1 PHE 115 CD2 PHE 115 CEl PHE 115 CE2 PHE 115 CZ PHE 115 C PHE 115 O PHE 115 N ASP 116 H ASP 116 CA ASP 116 CB ASP 116 CG ASP 116 ODi ASP 116 0D2 ASP 116 C ASP 116 O ASP 116 N CLE 117 H CLE 117 CA CLE 117 CS CLE 117 SG CLE 117 B CLE 117 C CLE 117 o CLE 117 N LEU 118 H LEU 118 -1.698 -2.060 -2.103 -2.511 -0.738 -3.386 -3.474 -4.389 -4.259 -5.698 -6.701 -8.145 -8.517 -9.136 -9.852 -10.475 -10.830 -5.598 -6.187 -4.853 -4.437 -4.649 -3.735 -4.448 -5.617 -3.831 -4.001 -4.399 -3.004 -2.749 -2.267 -1.156 0.032 1.502 -3.171 -3.040 -4.077 -4.145 -4.160 -6.104 -5.481 -6.519 -4.914 -6.787 -8.014 -6.012 -5.036 -6.580 -5.485 -5.914 -6.981 -5.237 -7.364 -5.615 -6.676 -7.604 678 -7.262 -6.379 -8.154 -7.493 -6.435 -6.109 -5.933 -9 .448 -10.547 -9.295 -8.387 -10.413 -9.892 -11.145 -9.640 -11. 348 -12.573 -10.772 -9.793 48.725 49.472 50.884 51. 915 51.236 49.134 49.197 48.721 48 .674 48.382 48 .003 48 .109 48.927 47.409 49 .044 47 .520 48.338 47.255 47.338 46.207 46.194 45.062 44.019 43 .187 43.476 42 .227 45.534 45.137 46.395 46.652 46.952 47 .847 48.309 49 .805 47.746 47 .655 48.533 48.594 1.00 1.00 1.00 1.00 1.00 1 .00 1.00 1.00 1. 00 1.00 1.00 1.00 1 .00 1.00 1 .00 1 .00 1 .00 1.00 1 .00 1.00 1.00 1.00 1 .00 1 00 S. 00 1.00 1 .00 1.00 1 .00 1.00 1.00 1.00 1.00 1.20 1.00 1.00 1.00 1.00 0.00 12.01 11.85 11.29 11.92 11.03 11.50 10.78 0.00 11.16 9.84 10.03 7 .64 11.26 9 .24 10.69 9.26 11.82 12.23 12.76 0.00 13.21 15 .79 18.80 22.22 23.70 12.02 12.26 12.55 0.00 15.65 16.88 24.55 27 .84 17.48 18 16.22 0.00 100 ATOM 1084 CA LEU 118 -5.004 -11.564 49.333 1.00 15.66 p

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1085 1086 1087 1088 1089 1090 1091 1092 1093 1094 1095 1096 1097 1098 1099 1100 1101 1102 1103 1104 1105 1106 1107 1108 1:09 ii0 ii! 1112 1113 1114 1115 1116 1117 1118 1119 1120 1121 1122

CB

CG

CD1 CD2

C

0

N

F

H

H

H-

LEU

LEU

LEU

LEU

LEU

LEU

ARG

H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NH1 ARG I ARG HI2 ARG NH2 ARG H21 ARG 1H22 ARG C ARG O ARG N AS? H ASP CA AS CB ASP CG AS? ODI ASP OD2 AS3 C ASP 0 ASP N ALA H ALA CA AL CB ALA C ALA O ALA 118 118 118 118 118 118 119 119 119 119 119 119 119 119 119 119 119 119 119 119 119 119 119 120 120 120 120 120 120 120 120 120 121 121 121 121 121 121 -5.621 -10.727 -4.653 -10.113 -5.420 -9.697 -3.561 -11.107 -6.107 -12.191 -6.496 -13.339 -6.603 -11.452 -6.276 -10.543 -7.654 -11.971 -8.187 -10.900 -8.923 -9.767 -9.927 -9.104 -9.383 -8.767 -9.540 -9.392 -8.678 -7.672 -8.412 -6.790 -8.728 -6.943 -7.872 -5.976 -8.256 -7.447 -8.466 -8.097 -7.723 -6.624 -7.161 -13.164 -7.940 -14.053 -5.870 -13.188 -5.289 -12.442 -5.294 -14.298 -3.790 -14.087 -3.118 -15.265 -3.371 -15.490 -2.341 -15.969 -5.544 -15.602 -6.080 -16.554 -5.192 -15.614 -4.782 -14.809 -5.366 -16.787 -4.778 -16.523 -6.825 -17.220 -7.132 -18.415 50.458 51.472 52.717 51.840 48.484 48.718 47.495 47.372 46.624 45.672 46.355 45.426 44.110 43.371 43 .837 44.789 45.724 44.576 42.600 41.867 42.397 45.823 45.491 45.514 45.768 44.766 44.576 43 .903 42.702 44.581 45.515 44.953 46.798 47 .181 47 .647 49 .029 47 .773 47.772 1.00 1.00 1.00 1.00 1.00 1.00 .00 i.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1 .00 1 .00 1.00 1.00 1.00 1.00 1 .00 1 .00 1 .00 1.00 1 .00 1.00 15.67 1.00 20.69 1.00 25.46 1.00 26.35 1.00 15.77 1.00 15.49 1.00 14.72 0.00 16.75 14.68 17.93 20.84 26.76 0.00 29.78 31.04 0.00 0.00 32.50 0.00 0.00 18 .07 21.21 17 0.00 17.83 22.04 23.22 26.00 27.30 16.21 14.21 13.03 0.00 13.21 11.07 11.40 11.87 101 ATOM 1123 N SEM 122 -7.721 -16.248 4.8 .0 97 47-885 1.00 9.79 ATOM 1124 H SEM 122 -7.400 -15.319 47.872 1.00 0.00 ATOM 1125 CA SEM 122 -9.141 -16.521 48.025 1.00 9.76 ATOM 1126 CB SEM 122 -9.884 -15.251 48.433 1.00 12.08 ATOM 1127 CG SEM 122 -9.471 -14.699 49.790 1.00 17.34 ATOM 1128 A SEM 122 -10.315 -12.991 50.177 1.00 20.79 ATOM 1129 CE SEM 122 -9.148 -12.427 51.564 1.00 22.20 ATOM 1130 C SEM 122 -9.752 -17.115 46.762 1.00 10.01 ATOM 1131 0 SEM 122 -10.609 -17.995 46.844 1.00 11.95 1 0 ATOM 1132 N VAL 123 -9.329 -16.627 45.600 1.00 10.94 ATOM 1133 H VAL 123 -8.673 -15.894 45.592 1.00 0.00 ATOM 1134 CA VAL 123 -9.836 -17.140 44.333 1.00 12.22 ATOM 1135 CB VAL 123 -9.371 -16.272 43.134 1.00 13.58 ATOM 1136 CG1 VAL 123 -9.759 -16.926 41.810 1.00 15.25 1 15 ATOM 1137 CG2 VAL 123 -10.003 -14.894 43.220 1.00 13.81 **ATOM 1138 c VAL 123 -9.367 -18.583 44.165 1.00 11.57 **ATOM 1139 0 VAL 123 -10.145 -19.454 43.786 1.00 15.13 ATOM 1140 N ARG 124 -8.105 -18.843 44.489 1.00 13.03 *ATOM 1141 H ARG 124 -7.519 -18.104 44.781 1.00 0.00 ATOM 1142 CA ARG 124 -7.559 -20.192 44.384 1.00 15.09 ATOM 1143 CB ARG 124 -6.089 -20.219 44.804 1.00 19.47 ATOM 1144 CG ARG 124 -5.177 -19.326 43.978 1.00 29.40 ATOM 1145 CD ARG 124 -3.720 -19.503 44.389 1.00 34.85 ATOM 1146 NE ARG 124 -3.238 -20.849 44.085 1.00 39.82 ATOM 1147 HE ARG 124 -3.340 -21.538 44.777 1.00 0.00 ATOM 1148 CZ ARG 124 -2.669 -21.201 42.934 1.00 40.38 ATOM 1149 NH1 ARG 124 -2.497 -20.304 41.967 1.00 40.47 ATOM 1150 H11 ARG 124 -2.791 -19.357 42.092 1.00 0.00 ATOM 1151 HH12 ARG 124 -2.060 -20.584 41.111 1.00 0.00 ATOM 1152 NH2 ARG 124 -2.295 -22.461 42.740 1.00 39.07 ATOM 1153 HH21 ARG 124 -2.439 -23.141 43.460 1.00 0.00 ATOM 1154 HH22 ARG 124 -1.862 -22.734 41.883 1.00 0.00 ATOM 1155 C ARG 124 -8.356 -21.143 45.271 1.00 13.87 ATOM 1156 0 ARG 124 -8.776 -22.210 44.829 1.00 11.56 ATOM 1157 N ASP 125 -8.581 -20.738 46.517 1.00 13.96 ATOM 1158 H ASP 125 -8.214 -19.874 46.802 1.00 0.00 ATOM 1159 CA ASP 125 -9.333 -21.554 47.464 1.00 14.81 ATOM 1160 CB ASP 125 -9.308 -20.925 48.861 1.00 18.19 ATOM 1161 CC ASP 125 -9.967 -21.807 49.908 1.00 20.88 102 ATOM 1162 ODI ASP 125 -10.978 -21.373 5096 102.1 50.496 1.00 26.61

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1163 1164 1165 1166 1167 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 1180 1181 1182 1183 1184 1185 1186 1187 1188 1189 1190 1191 1192 1193 1194 1195 1196 1197 1198 1199 1200 0D2 ASP 125 C ASP 125 O ASP 125 N TYR 126 H TYR 126 CA TYR 126 CB TYR 126 CC TYR 126 CD1 TYR 126 CEl TYR 126 CD2 TYR 126 CE2 TYR 126 CZ TYR 126 OH TYR 126 HH TYR 126 C TYR 126 O TYR 126 N VAL 127 H VAL 127 CA VAL 127 CB VAL 127 CG1 VAL 127 CG2 VAL 127 C VAL 127 o VAL 127 N ARC 128 H ARG 128 CA ARC 128 CB ARG 128 CG ARC 128 CD ARG 128 NE ARG 128 HE ARG 128 CZ ARC 128 NH1 ARG 128 HH11 ARG 128 HH12 ARC 128 NH2 ARC 128 -9.482 -10.770 -11.287 -11.407 -10.954 -12.773 -13.310 -14.764 -15.789 -17.129 -15.115 -16.453 -17.456 -18.781 -19.331 -12.825 -13.666 -11. 917 -11.265 -11.865 -10.846 -10.675 -11.320 -11.554 -12.166 -10.640 -10.202 -10.265 -9.071 -8.535 -7.466 -6.274 -5.736 -5.882 -6.592 -7.423 -6.310 -4.754 -22.937 -21. 783 -22.894 -20.747 -19.881 -20.879 -19.525 -19.552 -19.431 -19.440 -19.687 -19.699 -19 .573 -19.560 -19.523 -21. 880 -22. 779 -21.723 -21.000 -22 .608 -22.100 -23.120 -20.766 -24.049 -24.991 -24.213 -23.424 -25.536 -25.435 -26.774 -26.610 -25 .919 -26.363 -24.719 -24.062 -24.475 -23.161 -24.197 50.135 46.996 47.097 46.463 46.429 45.958 45.483 45.050 45.984 45.595 43.705 43.304 44.256 43 .871 44.667 44.799 44.779 43.838 43 .917 42.679 41. 628 40.506 41.050 43 .086 42 .577 44.036 44.413 44.519 45.464 45.921 46.986 46 .494 45.803 46.911 47 .822 48.195 48.136 46.451 1.00 20.43 1.00 13.18 1.00 14.12 1.00 12.51 1.00 0.00 1.00 14.80 1.00 16.19 1.00 19.94 1.00 22.56 1.00 25.33 1.00 21.52 1.00 22.94 1.00 24.54 1.00 25.75 1.00 0.00 1.00 14.74 1.00 12.46 1.00 14.94 1.00 0.00 1.00 15.31 1.00 16.12 1.00 14.89 1.00 14.29 1.00 15.31 1.00 14.57 1.00 15.60 1.00 0.00 1.00 18.18 1.00 20.53 1.00 26.43 1.00 31.14 1.00 32.88 1.00 0.00 1.00 33.15 1.00 33.64 1.00 0.00 1.00 0.00 1.00 31.81 103 ATOM 1201 HH21 ARG 128 -4.207 -24.708 45.789 1.00 0.00

S

*5

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1202 1203 1204 1205 1206 1207 1208 1209 1210 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 1222 1223 1224 1225 1226 1227 1228 1229 1230 1231 1232 1233 1234 1235 1236 1237 1238 1239 HH22 ARG 128 C ARG 128 0 ARG 128 N GLN 129 H GLN 129 CA GLN 129 CB GLN 129 CG GLN 129 CD GLN 129 OE1 GLN 129 NE2 GLN 129 HE21 GLN 129 HE22 GLN 129 C GLN 129 O GLN 129 N THR 130 H THR 130 CA THR 130 CB THR 130 OGI THR 130 HG1 THR 130 CG2 THR 130 C THR 130 O THR 130 N TRP 131 H TRP 131 CA TRP 131 CB TRP 131 CG TRP 131 CD2 TRP 131 CE2 TRP 131 CE3 TRP 131 CD1 TRP 131 NEl TRP 131 HE1 TRP 131 CZ2 TRP 131 CZ3 TRP 131 CH2 TRP 131 -4.451 -11.439 -11.724 -12.136 -11.861 -13.278 -13.783 -12.763 -12.195 -10.983 -13.066 -14.022 -12.673 -14.444 -15.075 -14.745 -14.243 -15.858 -16.267 -16.598 -17.447 -17.471 -15.639 -16.476 -14.524 -13.871 -14.248 -13.573 -14.368 -15.316 -15.833 -15.781 -14.349 -15.225 -15.376 -16.793 -16.737 -17.230 -23.298 -26.220 -27.386 -25.485 -24.558 -26.040 -25.056 -24.641 -25.806 -25.900 -26.693 -26.565 -27.439 -26.388 -27.427 -25.500 -24.663 -25.700 -24.365 -23.426 -23.676 -24.545 -26.749 -27.634 -26.660 -25.958 -27.599 -26.873 -25.715 -25.731 -24.419 -26.722 -24.433 -23.651 -22.692 -24.073 -26.376 -25.062 46.770 45.228 44.980 46.087 46.234 46.812 47.875 48.919 49.700 49.895 50.167 50.000 50.665 45.887 46.040 44.950 44.875 44.036 43.386 44.415 44.803 42.470 42.951 42.771 42.234 42.438 41.147 39.976 39.462 38.385 38.265 37.510 39.935 39.223 39.377 37.305 36.553 36.460 1.00 0.00 1.00 19.96 1.00 20.08 1.00 21.86 1.00 0.00 1.00 24.92 1.00 27.32 1.00 38.13 1.00 43.53 1.00 49.52 1.00 46.67 1.00 0.00 1.00 0.00 1.00 22.91 1.00 25.98 1.00 21.09 1.00 0.00 1.00 20.03 1.00 21.01 1.00 24.86 1.00 0.00 1.00 18.89 1.00 20.64 1.00 21.45 1.00 18.24 1.00 0.00 1.00 18.29 1.00 17.75 1.00 18.23 1.00 20.51 1.00 19.78 1.00 20.37 1.00 18.07 1.00 19.62 1.00 0.00 1.00 18.47 1.00 19.44 1.00 19.54 104 ATOM 1240 C 'TRP 131. -13.434 -28.831 4159 .0 171 41.539 1.00 17.51 p.

p p p

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1241 1242 1243 1244 1245 1246 1247 1248 1249 1250 1251 1252 1253 1254 1255 1256 1257 1258 1259 1260 1261 1262 1263 1264 1265 1266 1267 1268 1269 1270 1271 1272 1273 1274 1275 1276 1277 1278 CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS 0O r LS N LET) H LET) CA LET) CB LET) CG LET) CD1 LET) CD2 LET) C LET)- 0 LET) N G LT H G7 7j CA GLT CB GLT) CG GLT) CD GLT) OE1 GLU 0E2 GLU C GLI) 0 GLI) N GLY H GLY CA GLY C GLY 0 GLTY

TRP

LYS

LYS

LYS

LY ,S

LYS

131 132 132 132 132 132 132 132 132 132 132 132 132 132 133 133 133 133 133 133 133 133 133 134 134 134 134 134 134 134 134 134 134 135 135 135 135 135 -13.250 -29.734 -12.956 -28.863 -13.131 -28.128 -12.155 -29.977 -13.010 -31.246 -13.864 -31.290 -15.049 -30.351 -15.917 -30.429 -15.176 -30.035 -14.777 -29.086 -14.398 -30.705 -15.821 -30.030 -10.952 -30.279 -10.616 -31.441 -10.311 -29.227 -10.601 -28.334 -9.152 -29.376 -9.266 -28.439 -10.384 -28.729 -10.423 -27.640 -10.168 -30.093 -7.851 -29.107 -7.844 -28.489 -6.745 -29.561 -6.783 -30.056 -5.436 -29.365 -5.146 -30.478 -4.135 -30.097 -4.605 -28.933 -3.922 -27.885 -5.658 -29.065 -4.369 -29.349 -4.655 -29.660 -3.156 -28.946 -3.008 -28.662 -2.062 -28.894 -2.340 -27.998 -3.038 -26.986 40.718 42.783 43 .405 43.300 43 .476 4 4 .74 1 44.661 45.909 47. 141 47 .010 47.312 47.956 42 .410 42177 41.915 42 .179 41 .044 39.841 38 .840 37 .792 38.197 41.782 42 .843 41 .2'04 40.359 41. 810 42.821 43.901 44.762 44.772 45.426 40.720 39 .559 41.087 42.009 40 .133 38.941 39.062 1.00 17.01 1.00 17.08 1.00 0.00 1.00 21.35 1.00 22.55 1.00 27.05 1.00 28.94 1.00 27.71 1.00 28.94 1.00 0.00 1.00 0.00 1.00 0.00 1.00 21.09 1.00 22.12 1.00 22.01 1.00 0.00 1.00 24.78 1.00 24.76 1.00 23.74 1.00 18.82 1.00 20.87 1.00 26.48 1.00 26.77 1.00 31.08 1.00 0.00 1.00 36.68 1.00 42.39 1.00 50.47 1.00 54.00 1.00 56.35 1.00 55.94 1.00 36.98 1.00 37.05 1.00 37.39 1.00 0.00 1.00 38.80 1.00 39.61 1.00 40.95 105 ATOM 1279 N GLU 136 -1.816 -28.385 3.8. 10 89 37.781 1.00 38.99 ATOM 1280 H GLU

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1281 1282 1283 1284 1285 1287 1288 1289 1290 1291 1292 1293 1294 1295 1296 1297 1298 1299 1300 1301 1302 1303 1304 1305 1306 1307 1308 1309 1310 1311 1312 1313 1314 1315 1316 1317

GLU

ALA

ALA

ALA

CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GU CB ALA C ALA O ALA N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU 0 LEU N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU o GLU N GLN H GLN CA GLN CB GLN 136 136 136 136 136 136 136 136 136 137 137 137 137 137 137 138 138 138 138 138 138 138 138 138 139 139 139 139 139 139 139 139 139 139 140 140 140 140 -1.290 -29.209 -1.999 -27.616 -1.244 -28.259 0.134 -27.652 0.073 -26.157 0.533 -25.357 -0.437 -25.783 -3.454 -27.403 -3.795 -26.386 -4.304 -28.367 -3.975 -29.157 -5.729 -28.268 -6.440 -29.556 -6.314 -27.079 -7.031 -26.257 -5.963 -26.973 -5.350 -27.643 -6.435 -25.884 -5.909 -26.053 -6.161 -24.920 -7.648 -24.709 -5.493 -25.252 -5.932 -24.573 -6.686 -23.611 -4.649 -24.550 -4.110 -25.355 -4.003 -23.373 -2.546 -23.690 -1.524 -22.848 -1.489 -23.111 -2.188 -24.025 -0.743 -22.394 -4.726 -22.880 -4.906 -21.679 -5.130 -23.808 -4.957 -24.758 -5.845 -23.446 -6.008 -24.660 37.748 36.553 35.386 35.129 34.827 35.672 33.746 36.172 35.564 36.514 36.985 36.215 36.605 36.976 36.405 38.254 38.627 39.097 40.520 41.514 41. 716 42 .830 38.527 38.401 38.179 38.336 37.610 37.274 38.024 39.524 40.014 40.220 36.363 36.181 35.500 35.685 34.280 33 .356 1.00 0.00 1.00 38.69 1.00 43.51 1.00 51.02 1.00 54.54 1.00 54.76 1.00 57.49 1.00 35.47 1.00 33.83 1.00 32.94 1.00 0.00 1.00 31.07 1.00 31.83 1.00 27.50 1.00 29.33 1.00 24.80 1.00 0.00 1.00 23.90 1.00 21.92 1.00 21.33 1.00 22.45 1.00 21.62 1.00 26.43 1.00 25.96 1.00 30.25 1.00 0.00 1.00 32.41 1.00 34.88 1.00 40.02 1.00 42.46 1.00 46 .36 1.00 44.75 1.00 33 1.00 33 .01 1.00 36.05 1.00 0.00 1.00 38 .93 1.00 43.55 106 ATOM 1318 CG GLN 140 -4.703 -25.295 3291 .0 32.911 1.00 50.09 15 20 25 ATOM 1319 ATOM 1320 ATOM 1321 ATOM 1322 ATOM 1323 ATOM 1324 ATOM 1325 ATOM 1326 ATOM 1327 ATOM 1328 ATOM 1329 ATOM 1330 ATOM 1331 ATOM 1332 ATOM 1333 ATOM 1334 ATOM 1335 ATOM 1336 ATOM 1337 ATOM 1338 ATOM 1339 ATOM 1340 ATOM 1341 ATOM 1342 ATOM 1343 ATOM 1344 ATOM 1345 ATOM 1346 ATOM 1347 ATOM 1348 ATOM 1349 ATOM 1350 ATOM 1351 ATOM 1352 ATOM 1353 ATOM 1354 ATOM 1355 ATOM 1356

CD

OE1 NE2 HE2 1 HE2 2

C

0

N

H

CA

CB

C

0

N

H

GLN 140 GLN 140 GLN 140 GLN 140 GLN 140 GLN 140 GLN 140 ALA 141 ALA 141 ALA 141 ALA 141 ALA 141 ALA 141 ILE 142 ILE 142 CA ILE CB ILE CG2 ILE CG1 ILE CD ILE C ILE O ILE N ILE H ILE CA ILE CB ILE CG2 ILE CG1 ILE CD ILE C ILE O ILE N SER H SER CA SER CB SER OG SER 142 142 142 142 142 142 142 143 143 143 143 143 143 143 143 143 144 144 144 144 144 144 144 -3.702 -3 .865 -2.662 -2.611 -2.010 -7.220 -7.643 -7.904 -7.494 -9.238 -9.806 -9.297 -10.220 -8.321 -7 .602 -8.324 -7.237 -7.376 -5.833 -4.736 -8.189 -8.807 -7 .421 -6.962 -7.244 -6.211 -6.582 -4.804 -4.260 -8.592 -8.953 -9.349 -9.002 -10.652 -11.084 -10.009 -10.277 -11 .740 -24.272 -23 .688 -24. 039 -24.543 -23.377 -22.895 -21. 865 -23 .581 -24.378 -23.188 -24.218 -21.796 -21.034 -21.452 -22.089 -20.137 -19.979 -21.080 -19.991 -19.774 -19.035 -17.985 -19.288 -20.154 -18.299 -18.782 -18.283 -18.288 -18.790 -17.996 -16.835 -19.046 -19.948 -18.908 -20.261 -20.876 -21.685 -18.364 32.420 31.347 33.212 34.051 32.911 34.633 34.106 35 .543 35.939 35.974 36. 930 36.598 36.308 37.436 37.625 38.069 39.178 40.221 38.580 39.600 37.027 37 .156 35.974 35.905 34.917 33 .846 32 .451 34.195 35.509 34.266 34 .073 33 .977 34.145 33.345 32.786 32-.098 31.660 34.274 1.00 54.44 1.00 57.43 1.00 54.84 1.00 0.00 1.00 0.00 1.00 37.85 1.00 38.61 1.00 35.28 1.00 0.00 1.00 33.81 1.00 33.21 1.00 33 .71 1.00 33 .79 1.00 34.36 1.00 0.00 1.00 35.58 1.00 37.48 1.00 36.69 1.00 40.54 1.00 41.71 1.00 35.75 1.00 36.45 1.00 36.98 1.00 0.00 1.00 39.87 1.00 40.93 1.00 39.88 1.00 41.89 1.00 44.53 1.00 41.03 1.00 43 .88 1.00 41.09 1.00 0.00 1.00 42.72 1.00 43.70 1.00 48.58 1.00 0.00 1.00 42.64

SER

SER

107 ATOM 1357 0 SER 144 -12.612 -17.606 33 .845 1.00 43.71

B°

oo B oooo.

oooo*

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1358 N GLN 1359 H GLN 1360 CA GLN 1361 CB GLN 1362 CG GLN 1363 CD GLN 1364 OE1 GLN 1365 NE2 GLN 1366 HE21 GLN 1367 HE22 GLN 1368 C GLN 1369 o GLN 1370 N ALA 1371 H ALA 1372 CA ALA 1373 CB ALA 1374 C ALA 1375 o ALA 1376 N PRO 1377 CD PRO 1378 CA PRO 1379 CB PRO 1380 CG PRO 1381 C PRO 1382 0 PRO 1383 N GLN 1384 H GLN 1385 CA GLN 1386 CB GLN 1387 CG GLN 1388 CD GLN 1389 OEI GLN 1390 NE2 GLN 1391 HE21 GLN 1392 HE22 GLN 1393 C GLN 1394 o GLN 1395 N VAL 145 145 145 145 145 145 145 145 145 145 145 145 146 146 146 146 146 146 147 147 147 147 147 147 147 148 148 148 148 148 148 148 148 148 148 148 148 149 -11.692 -10.944 -12.691 -12.879 -13.600 -15.042 -15.882 -15.341 -14.639 -16.274 -12.442 -13.393 -11.175 -10.480 -10.786 -9.305 -11.638 -12.169 -11.807 -11.279 -12.614 -12.433 -12.233 -14.092 -14.694 -14.656 -14.092 -16.065 -16.476 -16.113 -16.424 -17 .548 -15.426 -14.538 -15.637 -16.403 -17.445 -15.530 -18.756 -19.324 -18.335 -19.419 -20.664 -20.391 -20.086 -20.506 -20.764 -20.325 -16.996 -16.275 -16.657 -17.248 -15.418 -15.113 -14.178 -13.570 -13.801 -14.419 -12.617 -12.486 -13.908 -12.720 -11.741 -13.915 -14.663 -14.164 -15.527 -15.735 -17.140 -17.624 -17.805 -17.383 -18.697 -14.109 -13.576 -14.677 35.543 35.823 36.520 37.585 37.092 36.708 37.562 35.419 34.792 35.164 37.204 37.503 37.423 37.094 38.102 37.861 37.818 38.748 36.535 35.303 36.213 34.699 34.258 36.595 37.039 36.452 36.166 36.753 36.191 34.728 34.245 34.391 33.673 33.597 33.339 38.246 38.643 39.070 1.00 42.82 1.00 0.00 1.00 42.48 1.00 43.50 1.00 46.68 1.00 49.02 1.00 49.76 1.00 48.88 1.00 0.00 1.00 0.00 1.00 41.52 1.00 42.42 1.00 41.08 1.00 0.00 1.00 42.09 1.00 43.64 1.00 42.22 1.00 40.36 1.00 42.75 1.00 42.03 1.00 42.24 1.00 42.92 1.00 42.35 1.00 41.91 1.00 43.04 1.00 42.14 1.00 0.00 1.00 41.99 1.00 46.02 1.00 52.36 1.00 56.58 1.00 60.22 1.00 57.78 1.00 0.00 1.00 0.00 1.00 40.35 1.00 42.32 1.00 35.77

B*

B. B

B

B

B B 108 S.

S

*5 S

S

S

*5*S S. S

S

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1396 1397 1398 1399 1400 1401 1402 1403 1404 1405 1406 1407 1408 1409 1410 1411 1412 1413 1414 1415 1416 1417 1418 1419 1420 1421 1422 1423 1424 1425 1426 1427 1428 1429 1430 1431 1432 1433 1434 H VAL CA VAL CB VAL CG1 VAL CG2 VAL C VAL 0 VAL N GLU H GLU CA GLU CB GU CG GLU CD GLU OE1 GU 0E2 GU C GLU O GLU N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS 0 LYS 149 149 149 149 149 149 149 150 150 150 150 150 150 150 150 150 150 151 151 151 151 151 151 151 151 151 15c;1 151 151 151 152 152 152 152 152 152 152 152 152 -14.725 -15.747 -15.297 -16 .047 -13.798 -15.034 -15 .112 -14 .375 -14.357 -13 .627 -13 .075 -11.690 -10.566 -9.728 -10.512 -14.431 -14.033 -15.565 -15.817 -16.432 -17.655 -18.689 -18 .247 -18 .173 -17 .791 -16.880 -18.521 -17.696 -16.886 -16.864 -17.288 -17.238 -17.768 -18.151 -18.970 -18.079 -19 .813 -16.736 -17.049 -15.083 -14.705 -16.056 -17.195 -16.245 -13 .569 -13 .469 -12.697 -12.827 -11.574 -10.693 -10.097 -11.124 -10.999 -12.052 -10.720 -10.555 -10.195 -10.387 -9.358 -8.926 -8 .102 -6.660 -5.880 -4.452 -4.410 -3.974 -3.973 -10.100 -9.553 -11. 352 -11.726 -12.195 -13.579 -14.587 -15.648 -13.875 -12.305 -12.034 38.684 40.512 41.116 40.452 40.942 41.242 42 .466 40.485 39 .513 41.049 39.922 40. 101 40.092 39 .171 40.930 42.038 43 .192 41.582 40.655 42 .406 41.590 42.352 42 .574 41.266 41.481 41.984 42 .046 40.563 43.656 44.761 43.468 42 .566 44 .556 44.008 44.830 45 .449 45.883 45.681 1.00 0.00 1.00 30.92 1.00 29.67 1.00 31.16 1.00 27.34 1.00 29.41 1.00 25.93 1.00 29.98 1.00 0.00 1.00 32.17 1.00 38.43 1.00 47.19 1.00 51.56 1.00 53.66 1.00 54.50 1.00 29.05 1.00 25.94 1.00 27.58 1.00 0.00 1.00 25.61 1.00 29.92 1.00 36.35 1.00 42.81 1.00 47.01 1.00 51.50 1.00 0.00 1.00 0.00 1.00 0.00 1.00 23.86 1.00 21.86 1.00 22.21 1.00 0.00 1.00 20.16 1.00 24.21 1.00 28.31 1.00 30.35 1.00 31.40 1.00 18.41

N

H

CA

CB

CG

CD1 CD2

C

0

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU 46.839 1.00 17.53 109 ATOM 1435 N ILE 153 -150 -1.5 4.33 .01.6 -15.501 -12.650 45.333 1.00 15.66 b p p p *5p* p p p p. p p p 1 5 20 25 ATOM 1436 ATOM 1437 ATOM 1438 ATOM 1439 ATOM 1440 ATOM 1441 ATOM 1442 ATOM 1443 ATOM 1444 ATOM 1445 ATOM 1446 ATOM 1447 ATOM 1448 ATOM 1449 ATOM 1450 ATOM 1451 ATOM 1452 ATOM 1453 ATOM 1454 ATOM 1455 ATOM 1456 ATOM 1457 ATOM 1458 ATOM 1459 ATOM 1460 ATOM 1461 ATOM 1462 ATOM 1463 ATOM 1464 ATOM 1465 ATOM 1466 ATOM 1467 ATOM 1468 ATOM 1469 ATOM 1470 ATOM 1471 ATOM 1472 ATOM 1473 H ILE 153 CA ILE 153 CB ILE 153 CG2 ILE 153 CG1 ILE 153 CD ILE 153 C ILE 153 O ILE 153 N ALA 154 H ALA 154 CA ALA 154 CB ALA 154 C ALA 154 O ALA 154 N THR 155 THR 155 CA THR 155 CB THR 155 OGi THR 155 HG1 THR 155 CG2 THR 155 C THP. 155 -15.300 -14.445 -13 .169 -11.944 -13.311 -14.378 -14.102 -13.967 -14.018 -14. 184 -13 .681 -13.464 -14.690 -14.309 -15.973 -16.254 -16.989 -18.355 -18.794 -18.242 -18.239 -17.152 -17 .628 -16.690 -16.290 -16 .816 -17 .514 -17 .884 -17 .083 -16.601 -15.502 -15 .498 -14.406 -14.471 -13 .086 -12.043 -13 .006 -12 .221 -12.822 -12.782 -13.439 -13.093 -14. 966 -15.489 -11. 446 -11. 377 -10.386 -10. 504 -9.052 -8.088 -8.462 -7.939 -8.553 -8.987 -7.997 -7 .861 -9 .139 -9 .431 -6.912 -8.754 -8.191 -10.000 -10.405 -10.803 -12.151 -12 .806 -13 .066 -13 .057 -11.024 -11.642 -10.461 -9.981 -10.594 -9 .841 -10.169 -10.725 44.388 46.327 45.728 46. 556 45. 702 44. 791 46.986 48.209 46. 187 45.232 46.693 45. 530 47.685 48.740 47.366 46.535 48.250 47.542 47.073 46.333 46.361 49.567 50. 556 49.608 48.811 50.816 50. 491 51. 710 52.183 49.683 51. 584 52.653 51. 076 50.225 51. 696 50.878 53.163 53.930 1.00 0.00 1.00 14.50 1.00 14.50 1.00 13.04 1.00 18.16 1.00 18.78 1.00 14.37 1.00 13.54 1.00 13.14 1.00 0.00 1.00 15.23 1.00 12.01 1.00 14.41 1.00 12.98 1.00 14.48 1.00 0.00 1.00 16.73 1.00 18.64 1.00 18.35 1.00 0.00 1.00 21.11 1.00 18.25 1.00 19.74 1.00 16.51 1.00 0.00 1.00 16.53 1.00 18.06 1.00 29.31 1.00 0.00 1.00 11.43 1.00 15.34 1.00 13.11 1.00 13 .94 1.00 0.00 1.00 13 .07 1.00 9.00 1.00 13 1.00 13.99 O THR N THR

THR

CA THR CB THR OGi TER HG1 TER CG2 THR C THR O THR N ALA

ALA

CA ALA CB ALA C ALA 0 ALA 110

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 0 ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

2 0 ATOM

ATOM

ATOM

ATOM

ATOM

2 5 ATOM

ATOM

ATOM

ATOM

ATOM

3 0 ATOM

ATOM

ATOM

ATOM

ATOM

3 5 ATOM

ATOM

ATOM

ATOM

ATOM

1474 1475 1476 1477 1478 1479 1480 1481 1482 1483 1484 1485 1486 1487 1488 1489 1490 1491 1492 1493 1494 1495 1496 1497 1498 1499 1500 1501 1502 1503 1504 1505 1506

HIS

HIS

CA HIS CB HIS CG HIS CD2 HIS NDI HIS HDI HIS CEI HIS ME2 HIS HE2 HIS C HIS

HIS

N GLU H GLU CA GLU CB GLU CG GLU CD GLU OEI GLU OE2 GLU C GLU 0 GLU N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NHI ARG 158 158 158 158 158 158 158 158 158 158 158 158 158 159 159 159 159 159 159 159 159 159 159 160 160 160 160 160 160 160 160 160 160 160 160 160 160 160 160 -13.805 -9.180 -14.354 -8.762 -13.809 -8.685 -14.763 -7.495 -16.195 -7.824 -17.222 -8.159 -16.705 -7.830 -16.243 -7.591 -17.984 -8.158 -18.321 -8.364 -19.222 -8.640 -14.173 -9.752 -13.696 -9.718 -14.999 -10.709 -15.284 -10.757 -15.451 -11.779 -16.550 -12.589 -17.756 -11.749 -18.864 -12.541 -18.718 -13.769 -19.892 -11.925 -14.354 -12.715 -14.571 -13.489 -13.178 -12.631 -13.026 -11.977 -12.052 -13.481 -11.340 -13.972 -12.276 -14.488 -11.522 -15.319 -10.957 -16.502 -10.3.55 -16.364 -11.186 -17.749 -11.965 -17.989 -12.388 -17.232 -12.144 -18.927 -10.669 -18.759 -10.108 -18.586 -10.839 -19.698 -11.046 -12.749 53.549 52.857 54.925 55.061 54.759 55.574 53.479 52.643 53.516 54.776 55.059 55.957 57.085 55.551 54.616 56.434 55.749 55.365 54.710 54.541 54.360 56.930 57.868 56.316 55.608 56.682 55.419 54.342 53 .331 53.971 54.730 53.578 52.530 52.035 52.235 54.266 55.074 53.968 57.562 1.00 12.36 1.00 0.00 1.00 13.60 1.00 13.48 1.00 12.57 1.00 7.29 1.00 12.96 1.00 0.00 1.00 9.68 1.00 10.23 1.00 0.00 1.00 13 .56 1.00 12.70 1.00 16.31 1.00 0.00 1.00 21.01 1. 00 21.32 1.00 26.36 1.00 30.62 1.00 36.67 1.00 36.45 1.00 23.45 1.00 26.52 1.00 23.94 1.00 0.00 1.00 24.21 1.00 26.28 1.00 29.92 1.00 35.32 1.00 38.70 1.00 0.00 1.00 41.35 1.00 41.68 1.00 0.00 1.00 0.00 1.00 43.07 1.00 0.00 1.00 0.00 1.00 23 .53 1507 HH11 ARG 1508 HH12 ARG 1509 NH2 ARG 1510 HH21 ARG 1511 HH22 ARG 1512 C ARG 111l 0* S. S

OOOS

0 0@

S

S.

0 5 5@ S S 0@0 S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1513 1514 1515 1516 1517 1518 1519 1520 1521 1522 1523 1524 1525 1526 1527 1528 1529 1530 1531 1532 1533 1534 1535 1536 1537 1538 1539 1540 1541 1542 1543 1544 1545 1546 1547 1548 1549 1550 1551 O ARG 160 N SEM 161 H SEM 161 CA SEM 161 CB SEM 161 CG SEM 161 A SEN 161 CE SEM 161 C SEM 161 O SEM 161 N PRO 162 CD PRO 162 CA PRO 162 CB PRO 162 CG PRO 162 C PRO 162 O PRO 162 N TRP 163 H TRP 163 CA TRP 163 CB TRP 163 CG TRP 163 CD2 TRP 163 CE2 TRP 163 CE3 TRP 163 CD1 TRP 163 NEI TRP 163 HEl TRP 163 CZ2 TRP 163 CZ3 TRP 163 CH2 TRP 163 C TRP 163 0 TRP 163 N TYR 164 H TYR 164 CA TYR 164 CB TYR 164 CG TYR 164 CD1 TYR 164 -10.110 -11.239 -12.039 -10.329 -10.334 -10. 002 -8.302 -7 .032 -10. 665 -11.834 -9.635 -8.216 -9.766 -8.326 -7.530 -10.669 -11.363 -10.633 -10.058 -11.419 -10.816 -10.401 -11. 256 -10.426 -12.641 -9.124 -9.133 -8.326 -10. 938 -13.151 -12.299 -12.915 -13 .662 -13.363 -12.770 -14.783 -15.034 -16.502 -17.209 -13.355 -11.444 -11. 020 -10.623 -9.192 -9.089 -9.909 -8.759 -10.643 -10.647 -10. 613 -10.576 -10 .629 -10.423 -11.077 -9.526 -9.716 -8.368 -8.304 -7 .214 -5.914 -5.950 -5.810 -5 .805 -5.682 -6.034 -5.941 -5.895 -5.674 -5.550 -5.548 -7.278 -6.417 -8.280 -8.981 -8.400 -8.901 -8.909 -7.717 58.090 57.716 57.353 58.501 57.963 56.474 56. 033 56. 813 59.990 60.370 60. 850 60. 459 62.314 62.779 61.704 62.867 63.869 62.215 61. 429 62.634 62 .076 60.614 59.471 58.326 59.303 60.126 58.754 58.178 57.030 58.012 56.894 62.354 62.816 61.607 61.266 61.317 59.893 59.522 59.384 1.00 23.47 1.00 21.32 1.00 0.00 1.00 18.41 1.00 18.20 1.00 17.50 1.00 19.57 1.00 18.11 1.00 16.60 1.00 17.62 1.00 16.11 1.00 17.97 1.00 17.72 1.00 17.28 1.00 19.86 1.00 18.86 1.00 17.42 1.00 18.22 1.00 0.00 1.00 14.35 1.00 12.07 1.00 11.68 1.00 10.99 1.00 11.80 1.00 12.54 1.00 10.94 1.00 12.98 1.00 0.00 1.00 11.75 1.00 15.49 1.00 11.88 1.00 13.04 1.00 14.42 1.00 13.04 1.00 0.00 1.00 14.03 1.00 11.45 1.00 10.45 1.00 11.63 S 6*0 SS 0

S

S S 112 ATOM 1552 CEl 'rYF 164 -18.568 -7.714 59.062 1.00 11.94 ATOM 1553 CD2 TYR. 164 -17.189 -10.107 59.326 1.00 11.28 ATOM 1554 CE2 TYR 164 -18.543 -10.114 59.002 1.00 12.61 ATOM 1555 CZ TYR 164 -19.225 -8.917 58.873 1.00 13.23 ATOM 1556 OH TYR 164 -20.563 -8.923 58.556 1.00 18.84 ATOM 1557 HH TYR. 164 -20.907 -8.037 58.691 1.00 0.00 ATOM 1558 C TYR 164 -15.466 -9.327 62.311 1.00 14.87 ATOM 1559 0 TYR 164 -15.013 -10.447 62.538 1.00 15.57 ATOM 1560 N HIS 165 -16.552 -8.846 62.908 1.00 15.89 ATOM 1561 H HIS 165 -16.875 -7.950 62.663 1.00 0.00 ATOM 1562 CA HIS 165 -17.315 -9.622 63.878 1.00 17.82 ATOM 1563 CB HIS 165 -17.376 -8.902 65.231 1.00 18.47 ATOM 1564 CG HIS 165 -16.045 -8.762 65.910 1.00 16.54 ATOM 1565 CD2 HIS 165 -14.915 -8.114 65.538 1.00 14.16 1 5 ATOM 1566 ND1 H IS 165 -15.776 -9.320 67.142 1.00 14.58 *ATOM 1567 HD1 HIS 165 -16.276 -9.959 67 .702 1.00 0.00 ATOM 1568 CEl HIS 165 -14.541 -9.018 67.500 1.00 15.81 :::ATOM 1569 NE2 HIS 165 -13.997 -8.289 66.543 1.00 15.66 ATOM 1570 HE2 HIS 1 65 -13.064 -8.031 66.556 1.00 0.00 20 ATOM 1571 c HIS 165 -18.713 -9.820 63 .321 1.00 18.44 ATOM 1572 0 HIS 165 -19.497 -8.876 63 .238 1.00 19.84 ATOM 1573 N SE? 166 -19.007 -11.056 62 .925 1.00 21.85 *ATOM 1574 H SER 166 -18.316 -11.751 62.997 1.00 0.00 ATOM 1575 CA SE? 166 -20.296 -11.434 62.345 1.00 24.63 ATOM 1576 CB SEF? 166 -20.289 -12.922 61.981 1.00 25.45 ATOM 1577 OG SE? 166 -19.253 -13.209 61 .056 1.00 36.62 *.ATOM 1578 HG SE? 166 -18.382 -13.082 61 .448 1.00 0.00 ATOM 1579 c SE? 166 -21.521 -11.138 63 .203 1.00 24.57 ATOM 1580 0 SE? 166 -22.593 -10.850 62.672 1.00 24.97 ATOM 1581 N SE? 167 -21.382 -11.261 64.518 1.00 25.49 ATOM 1582 H SER 167 -20.541 -11.538 64.921 1.00 0.00 ATOM 1583 CA SE? 167 -22.504 -11.000 65.408 1.00 30.48 ATOM 1584 CB SE? 167 -23.222 -12.301 65 .777 1.00 31.09 ATOM 1585 OG S Er 167 -23.709 -12.957 64.618 1.00 36.91 ATOM 1586 HG SE? 167 -24.177 -12.308 64.074 1.00 0.00 ATOM 1587 C SE? 167 -22.069 -10.265 66.662 1.00 30.67 ATOM 1588 0 SE? 167 -21.564 -10.863 67.617 1.00 34.44 ATOM 1589 N LEU 168 -22.237 -8.952 66.629 1.00 27.52 ATOM 1590 H LEU 168 -22.633 -8.515 65 .836 1.00 0.00 113

S

S

S

A

A

A

A

A

A

A

A

ATOM 1591 ATOM 1592 ATOM 1593 ATOM 1594 ATOM 1595 ATOM 1596 ATOM 1597 ATOM 1598 ATOM 1599 ATOM 1600 ATOM 1601 ATOM 1602 ATOM 1603 ATOM 1604 %TOM 1605 ATOM 1606 ATOM 1607 TOM 1608 TOM 1609 TOM 1610 TOM 1611 TOM 1612 TOM 1613 \TOM 1614 \TOM 1615 TOM 1616 CA LEU CB LEU CG LEU CDI LEU CD2 LEU C LEU 0 LEU N THR H THR CA THR CB THR OGI THR HG1 THR CG2 THR C THR O THR N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NH1 ARG 168 168 168 168 168 168 168 169 169 169 169 169 169 169 169 169 170 170 170 170 170 170 170 170 170 170 170 170 170 170 170 170 170 171 171 171 171 171 171 -21.894 -20.504 -19.283 -18.189 -19.596 -22.886 -23.127 -23.498 -23.297 -24.431 -25.503 -24.876 -25.601 -26.313 -23.547 -22.355 -24.125 -25.076 -23.383 -24.302 -23.645 -24.672 -24.099 -23.788 -23.966 -23.442 -23.176 -23.372 -24.327 -24.701 -24.185 -22.799 -21.631 -23 .603 -24.524 -23 .157 -24.296 -23 .890 -24.931 -8.096 -7.487 -8.162 -7.116 -8.715 -6.969 -6.325 -6.751 -7.292 -5.655 -5.944 -6.164 -6.350 -7.180 -4.494 -4.682 -3.304 -3.202 -2.125 -0 .907 0.392 1.495 2 .796 2.980 3 .775 4.933 5 .091 5.687 3.589 2.709 4.334 -2.329 -2.013 -2 .877 -3.101 -3 .114 -3.656 -3.861 -4.598 67.747 67.587 68.190 68.286 69.558 67.769 66.747 68.920 69.704 69.047 70.120 71.390 72.002 69.738 69.485 69.759 69.557 69.314 69.975 69 .956 70 .358 70 .345 70.649 71.549 69.762 70 .132 71 .081 69.486 68.501 68.207 67.852 71.375 71.616 72.284 72.035 73 .654 74.521 75.985 76.818 1.00 23.85 1.00 23.06 1.00 22.81 1.00 20.60 1.00 22.00 1.00 22.39 1.00 23.43 1.00 20.11 1.00 0.00 1.00 18.64 1.00 20.52 1.00 21.40 1.00 0.00 1.00 22.55 1.00 16.14 1.00 14.33 1.00 17.90 1.00 0.00 1.00 16.65 1.00 15.78 1.00 16.09 1.00 17.74 1.00 17.11 1.00 0.00 1.00 16.57 1.00 15.48 1.00 0.00 1.00 0.00 1.00 15.05 1.00 0.00 1.00 0.00 1.00 16.82 1.00 16.43 1.00 16.19 1.00 0.00 1.00 17.65 1.00 20.42 1.00 28.15 1.00 33.50

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1617 HHll ARG 1618 HH12 ARG 1619 NH2 ARG 1620 HH21 ARG 1621 HH22 ARG 1622 C ARG 1623 0 ARG 1624 N GLU 1625 H GLU 1626 CA GLU 1627 CB GLU 1628 CG GLU 1629 CD GLU 114

S

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ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1630 1631 1632 1633 1634 1635 1636 1637 1638 1639 1640 1641 1642 1643 1644 1645 1646 1647 1648 1649 1650 1651 1652 1653 1654 1655 1656 1657 1658 1659 1660 1661 1662 1663 1664 1665 1666 1667 1668 OE1 GLU 0E2 GLU C GLU 0 GLU N GLU H GLU CA GLtJ CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU O GLU N ALA H ALA CA ALA CB ALA C ALA o ALA N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU O GLU N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG 171 171 171 171 172 172 172 172 172 172 172 172 172 172 173 173 1.73 173 173 173 174 174 174 174 174 174 174 174 174 174 175 175 175 175 175 175 175 175 175 -24.529 -26.144 -21. 980 -20.990 -22.095 -22.905 -21. 041 -21. 497 -22.697 -23 .255 -23.063 -23.901 -19.780 -18 .674 -19.946 -20.848 -18.805 -19.273 -18.053 -16.831 -18.791 -19.767 -18 .178 -19.204 -19.696 -20.406 -20.943 -20.423 -17.517 -16.446 -18.144 -18.996 -17.592 -18.566 -18.072 -19.238 -20.332 -20.118 -21.602 -5 .400 -4 .371 -4.075 -3 .816 -5.187 -5.331 193 -7.427 -8.119 -9.223 -9.176 -10.141 -5.617 -5.933 -4.763 -4.556 -4.132 -3.292 -3.266 -3.338 -2.471 -2.481 -1.603 -0.636 0.413 1.582 2.438 1.658 -2 .418 -2 .059 -3.525 -3.758 -4.387 -5.516 -6.491 -7 .101 -7.531 -8 .137 -7 .152 77 .688 76.619 73.721 74.418 73 .001 72 .465 72 .977 72.206 72.818 71.940 70.706 72.486 72 .357 72.790 71.351 71 .029 70 .695 69 .520 71.703 71 .806 72 .471 72 .349 73 .471 74 .064 73.072 73 .734 73 .004 74.979 74 .574 75 .062 74 .953 74.523 75.987 76.317 77 .373 78.146 77 .274 76 .537 77 .416 1.00 35.78 1.00 38.13 1.00 15.35 1.00 13.06 1.00 16.60 1.00 0.00 1.00 16.42 1.00 18.60 1.00 24.77 1.00 30.30 1.00 30.79 1.00 35.30 1.00 15.63 1.00 18.34 1.00 16.15 1.00 0.00 1.00 13.89 1.00 14.91 1.00 11.93 1.00 12.06 1.00 13.97 1.00 0.00 1.00 13.42 1.00 12.52 1.00 13.96 1.00 16.34 1.00 17.65 1.00 20.00 1.00 14.72 1.00 16.13 1.00 16.98 1.00 0.00 1.00 17.73 1.00 20.45 1.00 27.83 1.00 32.77 1.00 38.89 1.00 0.00 1.00 41.12 115 ATOM 1669 NH1 ARG 175 -21.955 -6.333 78.400 1.00 40.50 ATOM 1670 HH11 ARC 175 -21.266 -5.992 79.041 1.00 0.00 ATOM 1671 HH12 ARG 175 -22.906 -6.052 78.508 1.00 0.00 ATOM 1672 NH2 ARG 175 -22.522 -7.585 76.563 1.00 42.19 ATOM 1673 HH21 ARC 175 -22.264 -8.200 75.819 1.00 0.00 ATOM 1674 HH22 ARG 175 -23.475 -7.301 76.675 1.00 0.00 ATOM 1675 C ARG 175 -16.245 -4.944 75.542 1.00 18.13 ATOM 1676 0 ARC 175 -15.305 -4.989 76.330 1.00 17.99 ATOM 1677 N LYS 176 -16.133 -5.319 74.270 1.00 19.22 1 0 ATOM 1678 H LYS 176 -16.906 -5.249 73.671 1.00 0.00 ATOM 1679 CA LYS 176 -14.872 -5.853 73.757 1.00 19.25 ATOM 1680 CB LYS 176 -15.070 -6.569 72.420 1.00 20.57 ATOM 1681 CC LYS 176 -15.907 -7.827 72.531 1.00 24.61 ATOM 1682 CD LYS 176 -15.949 -8.609 71.230 1.00 31.16 1 5 ATOM 1683 CE LYS 176 -14.759 -9.547 71.088 1.00 36.55 ATOM 1684 NZ LYS 176 -13.455 -8.837 70.995 1.00 41.60 *ATOM 1685 HZ1 LYS 176 -13.289 -8.308 71.876 1.00 0.00 :::ATOM 1686 HZ2 LYS 176 -13.483 -8.179 70.192 1.00 0.00 ATOM 1687 HZ3 LYS 176 -12.687 -9.525 70.849 1.00 0.00 ATOM 1688 C LYS 176 -13.806 -4.776 73.622 1.00 19.16 **ATOM 1689 0 LYS 176 -12.645 -5.006 73.952 1.00 20.81 ATOM 1690 N LEU 177 -14.199 -3.597 73.150 1.00 18.33 .ATOM 1691 H LEU 177 -15.133 -3.466 72.878 1.00 0.00 ATOM 1692 CA LEU 177 -13.251 -2.499 72.994 1.00 18.62 ATOM 1693 CB LEU 177 -13.857 -1.375 72.153 1.00 14.79 ATOM 1694 CC LEU 177 -14.119 -1.701 70.681 1.00 14.52 ATOM 1695 CD1 LEU 177 -14.746 -0.502 70.016 1.00 14.81 ATOM 1696 CD2 LEU 177 -12.833 -2.073 69.972 1.00 12.01 ATOM 1697 C LEU 177 -12.742 -1.950 74.328 1.00 19.76 ATOM 1698 0 LEU 177 -11.562 -1.628 74.456 1.00 20.72 ATOM 1699 N TYR 178 -13.632 -1.839 75.312 1.00 20.07 ATOM 1700 H TYR 178 -14.555 -2.105 75.139 1.00 0.00 ATOM 1701 CA TYR 178 -13.263 -1.334 76.634 1.00 21.20 ATOM 1702 CB TYR 178 -14.507 -0.935 77.425 1.00 18.72 ATOM 1703 CG TYR 178 -15.063 0.420 77.073 1.00 16.53 ATOM 1704 CD1 TYR 178 -14.238 1.543 77.029 1.00 17.03 ATOM 1705 CEl TYR 178 -14.752 2.796 76.738 1.00 14.85 ATOM 1706 CD2 TYR 178 -16.418 0.587 76.813 1.00 15.41 ATOM 1707 CE2 TYR 178 -16.942 1.833 76.520 1.00 14.24 -116 ATOM 1708 CZ TYR 178 -16.105 2.935 76.485 1.00 15.80

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1709 1710 1711 1712 1713 1714 1715 1716 1717 1718 1719 1720 1721 1722 1723 1724 1725 1726 1727 1728 1729 1730 1731 1732 1733 1734 1735 1736 1737 1738 1739 1740 1741 1742 1743 1744 1745 1746

TYR

TYR

TYR

TYR

SER

SER

SER

SER

SER

SER

SER

SER

GLY

GLY

CA GLY C GLY O GLY N ALA H ALA CA ALA CB ALA C ALA O ALA 178 178 178 178 179 179 179 179 179 179 179 179 180 180 180 180 180 181 181 181 181 181 181 182 182 182 182 182 182 182 182 182 182 182 182 183 183 183 -16.624 -17.593 -12.471 -11.596 -12.791 -13.473 -12.116 -13.067 -14.265 -14.778 -10.869 -10.909 -9.765 -9.787 -8.516 -7.445 -7.400 -6.590 -6.697 -5.508 -4.423 -6.006 -5.331 -7.179 -7.676 -7.772 -8.274 -9.511 -10.189 -10.327 -10.616 -10.461 -11.079 -6.832 -6.892 -5.972 -5.956 -5.036 4.177 4.110 -2.349 -1.986 -3.622 -3.885 -4.680 -5.861 -5.444 -5.012 -5.126 -6.065 -4.432 -3.665 -4.773 -3.734 -3.126 -3.519 -4.028 -2.549 -2.857 -1.111 -0.165 -0.953 -1.742 0.365 0.993 0.332 1.192 0.796 2.383 2.650 2.922 1.332 2.548 0.789 -0.170 1.606 76.198 76.183 77.446 78.233 77.266 76.617 77.998 78.220 78.868 78.177 77.251 76.456 77.498 78.115 76.846 77.103 78.171 76.109 75.282 76.222 75.197 76.055 76.465 75.446 75.154 75.214 76.521 77.103 78.152 79.308 77.752 76.828 78.427 74.497 74.703 73.643 73.460 72.891 1.00 17.17 1.00 0.00 1.00 24.65 1.00 26.95 1.00 31.05 1.00 0.00 1.00 35.86 1.00 37.01 1.00 38.69 1.00 0.00 1.00 39.08 1.00 42.60 1.00 42.38 1.00 0.00 1.00 45.79 1.00 47.21 1.00 47.24 1.00 48.92 1.00 0.00 1.00 50.24 1.00 49.84 1.00 51.23 1.00 54.12 1.00 50.07 1.00 0.00 1.00 47.88 1.00 49.86 1.00 53.43 1.00 57.83 1.00 60.70 1.00 58.70 1.00 0.00 1.00 0.00 1.00 43.44 1.00 41.92 1.00 39.92 1.00 0.00 1.00 36.35

N

H

CA

CB

CG

CD

OE1 NE2 HE21 HE22

C

O

N

H

CA

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

THR

THR

THR

117 ATOM 1747 CB THR 183 -3.864 0.758 72.357 1.2Z 38.51 ATOM 1748 OGi THR 183 -4.351 -0.519 71.923 1.00 42.00 ATOM 1749 HG1 THR 183 -3.917 -0.732 71.092 1.00 0.00 ATOM 1750 CG2 THR 183 -2.830 0.542 73.457 1.00 39.77 ATOM 1751 C THR 183 -5.758 2.321 71.749 1.00 32.35 ATOM 1752 0 THR 183 -6.676 1.772 71.132 1 00 29.04 ATOM 1753 N ASP 184 -5.367 3.567 71.508 1.00u 27.99 ATOM 1754 H ASP 184 -4.644 3.943 72.040 1.-03 0.00 ATOM 1755 CA ASP 184 -5.975 4.376 70.460 1.00 27.05 1 0 ATOM 1756 CB ASP 184 -5.285 5.742 70.374 1.00 27.76 ATOM 1757 CG ASP 184 -5.617 6.647 71.553 1.00 29.09 ATOM 1758 ODi ASP 184 -4.767 7.483 71.914 1.00 30.44 ATOM 1759 0D2 ASP 184 -6.729 6.539 72.109 1.00 30.19 ATOM 1760 c ASP 184 -5.973 3.701 69.092 1.00 23.21 1 5 ATOM 1761 0 ASP 184 -5.000 3.054 68.704 1.Z3 22.81 *ATOM 1762 N GLY 185 -7.088 3.826 68.385 1.:0 22.28 *ATOM 1763 H GLY 185 -7.863 4.278 68.784 1.00 0.00 *ATOM 1764 CA GLY 185 -7.200 3.235 67.068 1 .00 20.98 ATOM 1765 C GLY 185 -7.690 1.800 67.065 1.00 20.58 20 ATOM 1766 0 GLY 185 -7.879 1.223 65.994 1.00 21.98 ATOM 1767 N LYS 186 -7.847 1.198 68.241 1.00 19.39 ATOM 1768 H LYS 186 -7.620 1.668 69.072 1.00 0.00 ATOM 1769 CA LYS 186 -8.343 -0.173 68.330 1.00 19.96 ATOM 1770 CB LYS 186 -8.385 -0.628 69.790 1.00 24.49 ATOM 1771 CG LYS 186 -8.935 -2.022 69.996 1.00 30.49 ATOM 1772 CD LYS 186 -8.020 -3.081 69.408 1 .00 39.02 ATOM 1773 CE LYS 186 -6.799 -3.343 70.288 1.00 47.08 ATOM 1774 NZ LYS 186 -5.832 -2.209 70.348 1.30 51.52 ATOM 1775 HZ1 LYS 186 -6.284 -1.364 70.753 1.CO 0.00 ATOM 1776 HZ2 LYS 186 -5.492 -1.990 69.391 1.00 0.00 ATOM 1777 HZ3 LYS 186 -5.026 -2.478 70.946 1.00 0.00 ATOM 1778 c LYS 186 -9.753 -0.153 67.742 1.00 17.33 ATOM 1779 0 LYS 186 -10.603 0.617 68.198 1.00 17.32 ATOM 1780 N PHE 187 -10.008 -1.010 66.756 1.00 14.12 ATOM 1781 H PHE 187 -9.312 -1.637 66.467 1.00 0.00 ATOM 1782 CA PHE 187 -11.305 -1.032 66.092 1.00 10.45 ATOM 1783 CB PHE 187 -11.202 -0.237 64.786 1.00 11.01 ATOM 1784 CG PHE 187 -10.455 -0.967 63.697 1.00 12.30 ATOM 1785 CD1 PHE 187 -11.142 -1.525 62.618 1.00 11.77 118

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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ATOM

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ATOM

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ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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ATOM

ATOM

1786 1787 1788 1789 1790 1791 1792 1793 1794 1795 1796 1797 1798 1799 1800 1801 1802 1803 1804 1805 1806 1807 1808 1809 1810 1811 1812 1813 1814 1815 1816 1817 1818 1819 CD2 PHE CE1 PHE CE2 PHE CZ PHE C PHE O PHE N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NH1 ARG 187 187 187 187 187 187 188 188 188 188 188 188 188 188 188 189 189 189 189 189 189 189 189 189 190 190 190 190 190 190 190 190 190 190 190 190 190 190 190 -9.073 -10.461 -8.385 -9.081 -11.844 -11;157 -13.071 -13.567 -13.752 -14.276 -15.280 -16.689 -15.290 -14.888 -15.359 -15.286 -14.863 -16.363 -15.845 -16.568 -17.908 -16.725 -17.449 -17.160 -18.696 -18.893 -19.803 -20.199 -20.586 -20.747 -20.865 -20.054 -21.993 -23.133 -23.143 -23.970 -21.975 -21.118 -22.814 -1.137 63.770 -2.246 61.635 -1.857 62.788 -2.411 61.723 -2.421 65.754 -3.432 65.903 -2.437 65.243 -1.591 65.168 -3.644 64.802 -4.474 65.988 -3.955 67.030 -3.832 66.447 -4.941 68.190 -3.218 63.881 -2.082 63.956 -4.107 62.980 -4.989 62.944 -3.830 62.039 -3.967 60.597 -3.364 59.379 -4.020 59.126 -1.869 59.551 -4.858 62.332 -6.037 62.539 -4.416 62.364 -3.469 62.193 -5.313 62.658 -5.183 64.137 -3.758 64.560 -3.613 66.072 -2.210 66.479 -1.759 66.795 -1.501 66.454 -2.044 66.050 -3.001 65.758 -1.501 66.030 -0.220 66.799 0.212 67.080 0.312 66.777 1.00 10.05 1.00 10.76 1.00 10.66 1.00 8.89 1.00 11.49 1.00 12.56 1.00 11.03 1.00 0.00 1.00 10.57 1.00 13.68 1.00 12.79 1.00 12.29 1.00 10.52 1.00 10.06 1.00 11.34 1.00 11.08 1.00 0.00 1.00 11.26 1.00 14.05 1.00 18.08 1.00 20.55 1.00 21.24 1.00 10.17 1.00 9.97 1.00 8.42 1.00 0.00 1.00 10.21 1.00 12.50 1.00 11.39 1.00 10.81 1.00 10.25 1.00 0.00 1.00 8.67 1.00 8.01 1.00 0.00 1.00 0.00 1.00 11.12 1.00 0.00 1.00 0.00

C

1820 HH11 ARG 1821 HH12 ARG 1822 NH2 ARG 1823 HH21 ARG 1824 HH22 ARG 119

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

*ATOM

ATOM

ATOM

ATOM

ATOM

1825 1826 1827 1828 1829 1830 1831 1832 1833 1834 1835 1836 1837 1838 1839 1840 1841 1842 1843

ARG

ARC

PRO

PRO

PRO

PRO

PRO

PRO

PRO

ARG

ARC

ARC

ARC

ARG

ARG

ARC

ARC

ARG

ARG

1844 HH11 ARG 1845 HH12 ARC 1846 NH2 ARG 1847 HH21 ARG 1848 HH22 ARC 190 190 191 191 191 191 191 191 191 192 192 192 192 192 192 192 192 192 192 192 192 192 192 192 192 192 193 193 193 193 193 193 193 193 193 193 193 193 193 -20.996 -21.172 -21.785 -21.581 -22.960 -23 .281 -22.890 -24.081 -24. 039 -25.036 -25.006 -26.164 -26.369 -25.210 -25.445 -26.554 -26.455 -27.707 -27.925 -27.221 -28.799 -28.643 -28.468 -29.515 -27.406 -27.345 -28.523 -28.484 -29.773 -30.876 -30.577 -31 .765 -31.490 -32.702 -33 .436 -33.047 -32.473 -30.226 -30.611 -4.977 -3 .826 -5.991 -7 .440 -5 .721 -7.094 -8.023 -5.222 -5.444 -4.492 -4.277 -3 .988 -2 .489 -1.623 -0.158 0.404 0 .472 0 .809 0.718 0 .344 1.013 1.322 1 .402 1.625 -4 .779 -5.612 -4.532 -3.869 -5.232 -4.793 -5.067 -4.694 -4 .992 -4.794 -5 .457 -3 .819 -4.984 -5 .004 -5.950 61.789 61. 380 61. 416 61.603 60.587 60.004 61. 119 61. 500 62.712 60.937 59.982 61. 712 61.458 61.914 61.606 62.374 63 .346 61.849 60.544 59 .941 60.162 62.631 63 .611 62.246 61.311 60.404 61.988 62.709 61.690 62.654 64.117 64.990 66.457 67.307 66 .987 67 .206 68.304 60.246 59 .557 1.00 12.50 1.00 14.16 1.00 14.16 1.00 14.81 1.00 14.23 1.00 15.24 1.00 16.17 1.00 14.24 1.00 15.68 1.00 15.51 1.00 0.00 1.00 18.28 1.00 13.36 1.00 11.77 1.00 12.79 1.00 13.77 1.00 0.00 1.00 15.28 1.00 14.55 1.00 0.00 1.00 0.00 1.00 16.15 1.00 0.00 1.00 0.00 1.00 20.44 1.00 21.80 1.00 26.86 1.00 0.00 1.00 30.35 1.00 34.92 1.00 42.06 1.00 48.13 1.00 52.32 1.00 53.88 1.00 0.00 1.00 0.00 1.00 0.00 1.00 32.33 1.00 33.07

ATOM

ATOM 1849 ATOM 1850 ATOM 1851 ATOM 1852 ATOM 1853 ATOM 1854 ATOM 1855 ATOM 1856 ATOM 1857 ATOM 1858 ATOM 1859 ATOM 1860 ATOM 1861 ATOM 1862 ATOM 1863 C ARC o ARC N LYS H LYS CA LYS CB LYS CC LYS CD LYS CE LYS NZ LYS H1-i LYS HZ2 LYS HZ3 LYS C LYS 0 LYS 120 ATOM 1864 N GLU 194 -30.176 -3.751 59.795 1.00 31.89

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1865 1866 1867 1868 1869 1870 1871 1872 1873 1874 1875 1876 1877 1878 1879 1880 1881 CB GLU CG GLU CD GLU OE1 GLU OE2 GLU C GLU O GLU N GLN H GLN CA GLN CB GLN CG GLN CD GLN OE1 GLN NE2 GLN

GLU

GLU

1882 HE21 GLN 1883 HE22 GLN 194 194 194 194 194 194 194 194 194 195 195 195 195 195 195 195 195 195 195 195 195 196 196 196 196 196 197 197 197 197 197 197 197 197 197 198 198 198 -29.824 -30.575 -30.744 -32.021 -32.036 -32.968 -31.128 -29.541 -28.362 -29.986 -30.939 -29.097 -29.866 -30.238 -29.120 -29.252 -28.016 -27.917 -27.317 -28.477 -29.171 -27.170 -26.647 -26.491 -25.943 -25.454 -26.067 -26.503 -25.548 -26.665 -27.334 -27.449 -27.667 -24.652 -24.952 -23.539 -23.392 -22.542 -3.055 -3.401 -1.884 -1.301 -1.294 -1.885 -0.694 -3.882 -3.556 -4.651 -4.860 -5.168 -6.090 -7.431 -8.457 -9.457 -8.216 -7.416 -8.894 -4.024 -3.094 -4.095 -4.854 -3.050 -1.969 -0.946 -2.166 -2.975 -1.203 -0.454 -1.352 -2.142 0.147 -1.933 -3.057 -1.294 -0.390 -1.834 60.377 1.00 0.00 58.430 1.00 31.91 58.274 1.00 32.74 58.861 1.00 35.26 60.376 1.00 36.36 60.956 1.00 40.45 60.989 1.00 38.26 57.424 1.00 30.11 57.536 1.00 31.42 56.438 1.00 30.67 56.409 1.00 0.00 55.405 1.00 30.73 54.460 1.00 37.53 55.070 1.00 48.32 54.969 1.00 54.80 54.264 1.00 59.01 55.669 1.00 57.50 56.226 1.00 0.00 55.589 1.00 0.00 54.617 1.00 27.43 54.209 1.00 26.89 54.410 1.00 24.53 54.751 1.00 0.00 53.672 1.00 23.48 54.579 1.00 22.43 54.094 1.00 21.55 55.891 1.00 19.48 56.238 1.00 0.00 56.852 1.00 17.30 57.610 1.00 18.42 58.501 1.00 18.98 57.983 1.00 0.00 56.635 1.00 17.56 57.841 1.00 16.36 58.261 1.00 16.10 58.178 1.00 13.90 57.840 1.00 0.00 59.092 1.00 13.70 r 1884 1885 1886 1887 1888 1889 1890 1891 1892 1893 1894 1895 1896 1897 1898 1899 1900 1901 1902

GLN

GLN

GLY

GLY

CA GLY C GLY O GLY N THR H THR CA THR CB THR OG1 THR HG1 THR CG2 THR C THR O THR N TYR H TYR CA TYR 121 ATOM 1903 ATOM 1904 ATOM 1905 ATOM 1906 ATOM 1907 ATOM 1908 ATOM 1909 ATOM 1910 ATOM 1911 ATOM 1912 ATOM 1913 ATOM 1914 ATOM 1915 ATOM 1916 1 5 ATOM 1917 ATOM 1918 ATOM 1919 ATOM 1920 ATOM 1921 ATOM 1922 ATOM 1923 ATOM 1924 ATOM 1925 ATOM 1926 ATOM 1927 ATOM 1928 ATOM 1929 ATOM 1930 ATOM 1931 ATOM 1932 ATOM 1933 ATOM 1934 ATOM 1935 ATOM 1936 ATOM 1937 ATOM 1938 ATOM 1939 ATOM 1940 ATOM 1941 CB TYR CG TYR CD1 TYR CE1 TYR CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR C TYR O TYR N ALA H ALA CA ALA CB ALA C ALA O ALA N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N SER H SER CA SER CB SER OG SER HG SER C SER O SER N LEU H LEU CA LEU CB LEU CG LEU 198 198 198 198 198 198 198 198 198 198 198 199 199 199 199 199 199 200 200 200 200 200 200 200 200 200 201 201 201 201 201 201 201 201 202 202 202 202 202 -21.324 -21.644 -22.117 -22.441 -21.498 -21.817 -22.289 -22.612 -22.386 -22.101 -22.450 -21.317 -21.033 -20.833 -21.628 -19.363 -18.900 -18.624 -19.053 -17.206 -16.483 -15.092 -14.463 -14.204 -17.122 -17.605 -16.590 -16.248 -16.465 -17.216 -18.576 -18.554 -14.998 -14.274 -14.538 -15.116 -13.155 -12.259 -12.277 -2.317 -3.336 -2.941 -3.876 -4.699 -5.643 -5.226 -6.159 -7.044 -0.708 0.448 -1.033 -1.954 -0.012 -0.023 -0.225 -1.361 0.876 1.732 0.870 1.830 1.470 2.731 0.905 1.389 2.483 0.577 -0.304 0.972 -0.016 -0.156 -0.583 1.007 0.031 2.145 2.931 2.258 2.865 4.272 58.302 57.239 55.988 55.016 57.490 56.525 55.290 54.330 54.647 60.006 59.783 61.019 61.164 61.927 63.221 62.210 62.357 62.204 62.000 62.492 61.550 61.028 60.451 62.129 63.927 64.225 64.829 64.561 66.223 67.121 66.728 65.856 66.610 66.405 67.112 67.224 67.535 66.439 65.816 1.00 15.79 1.00 16.67 1.00 16.60 1.00 18.00 1.00 17.21 1.00 20.80 1.00 20.28 1.00 23.06 1.00 0.00 1.00 12.46 1.00 15.43 1.00 12.73 1.00 0.00 1.00 10.15 1.00 11.67 1.00 11.06 1.00 11.49 1.00 10.36 1.00 0.00 1.00 9.26 1.00 12.13 1.00 17.52 1.00 19.60 1.00 20.00 1.00 10.58 1.00 11.51 1.00 10.65 1.00 0.00 1.00 11.10 1.00 11.49 1.00 13.41 1.00 0.00 1.00 13.09 1.00 15.42 1.00 13.25 1.00 0.00 1.00 14.15 1.00 16.72 1.00 18.51 r 122 ATOM 1942 ATOM 1943 ATOM 1944 ATOM 1945 ATOM 1946 ATOM 1947 ATOM 1948 ATOM 1949 ATOM 1950 ATOM 1951 ATOM 1952 ATOM 1953 ATOM 1954 ATOM 1955 ATOM 1956 15 ATOM 1957 ATOM 1958 ATOM 1959 ATOM 1960 20 ATOM 1961 ATOM 1962 ATOM 1963 ATOM 1964 ATOM 1965 ATOM 1966 ATOM 1967 ATOM 1968 ATOM 1969 ATOM 1970 ATOM 1971 ATOM 1972 ATOM 1973 ATOM 1974 ATOM 1975 ATOM 1976 ATOM 1977 ATOM 1978 ATOM 1979 ATOM 1980 CD1 LEU 202 CD2 LEU 202 C LEU 202 O LEU 202 N ILE 203 H ILE 203 CA ILE 203 CB ILE 203 CG2 ILE 203 CG1 ILE 203 CD ILE 203 C ILE 203 O ILE 203 N TYR 204 H TYR 204 CA TYR 204 CB TYR 204 CG TYR 204 CD1 TYR 204 CE1 TYR 204 CD2 TYR 204 CE2 TYR 204 CZ TYR 204 OH TYR 204 HH TYR 204 C TYR 204 O TYR 204 N GLY 205 H GLY 205 CA GLY 205 C GLY 205 O GLY 205 N LYS 206 H LYS 206 CA LYS 206 CB LYS 206 CG LYS 206 CD LYS 206 CE LYS 206 -13.589 4.533 -11.956 5.347 -13.054 3.024 -13.968 3.753 -11.973 2.796 -11.290 2.170 -11.777 3.470 -11.514 2.444 -10.279 1.623 -11.419 3.146 -11.469 2.190 -10.669 4.517 -9.645 4.288 -10.940 5.707 -11.801 5.874 -9.997 6.809 10.257 7.691 -9.371 8.909 -7.983 8.783 -7.160 9.905 -9.917 10.189 -9.102 11.320 65.121 1.00 18.26 66.840 68.843 69.224 69.567 69.241 70.835 71.974 71.687 73.326 74.496 70.703 70.048 71.226 71.657 71.186 69.960 69.903 69.891 69.885 69.901 69.894 69.887 69.889 69.817 72.465 72.792 73.199 72.920 74.446 75.442 76.075 75.533 74.946 76.437 77.900 78.359 79.874 80.300 1.00 21.05 1.00 15.33 1.00 14.20 1.00 18.07 1.00 0.00 1.00 19.49 1.00 18.21 1.00 21.96 1.00 21.52 1.00 21.43 1.00 20.13 1.00 20.26 1.00 20.23 1.00 0.00 1.00 21.84 1.00 23.09 1.00 28.63 1.00 31.65 1.00 35.44 1.00 31.96 1.00 36.73 1.00 37.11 1.00 43.01 1.00 0.00 1.00 21.93 1.00 20.87 1.00 22.69 1.00 0.00 1.00 23.60 1.00 23.74 1.00 26.62 1.00 22.74 1.00 0.00 1.00 22.71 1.00 26.75 1.00 34.97 1.00 40.88 1.00 45.58 -7.726 -6.915 -7.453 -10.164 -11.271 -9.069 -8.223 -9.117 -10.061 -10.865 -9.993 -9.361 -10.834 -10.498 -9.177 -9.136 -7.962 11.171 12.283 13.075 7.618 8.048 7.796 7.424 8.540 7.891 8.572 6.565 6.092 5.784 6.085 5.500 5.336 4.464 123 ATOM 1981 NZ LYS 206 ATOM 198 NZ LYS 206-7.989 4.126 81.753 1.00 48.73 ATOM 1982 HZ1 LYS 206 -8.863 3.613 81.978 1.00 0.00 ATOM 1983 HZ2 LYS 206 -7.937 4.997 82.313 1.00 0.00 ATOM 1984 HZ3 LYS 206 -7.170 3.524 81.979 1.00 0.00 ATOM 1985 C LYS 206 -12.326 5.963 76.195 1.00 21.73 ATOM 1986 0 LYS 206 -13.132 5.757 77.093 1.00 21.98 ATOM 1987 N THR 207 -12.685 6.330 74.972 1.00 20.32 ATOM 1988 H THR 207 -12.028 6.508 74.270 1.00 0.00 ATOM 1989 CA THR 207 -14.079 6.524 74.604 1.00 21.18 ATOM 1990 CB THR 207 -14.401 8.020 74.393 1.00 23.74 ATOM 1991 OGi THR 207 -13.997 8.769 75.547 1.00 30.73 ATOM 1992 HG1 THR 207 -13.029 8.728 75.573 1.00 0.00 ATOM 1993 CG2 THR 207 -15.888 8.214 74.174 1.00 26.96 ***ATOM 1994 C THR 207 -14.309 5.776 73.296 1.00 17.81 1 5 ATOM 1995 0 THR 207 -13.429 5.741 72.443 1.00 17.93 ATOM 1996 N VAL 208 -15.469 5.151 73.150 1.00 18.45 00.ATOM 1997 H VAL 208 -16.138 5.204 73.866 1.00 0.00 .*.ATOM 1998 CA VAL 208 -15.776 4.406 71.935 1.00 17.67 ATOM 1999 CB VAL 208 -16.454 3.040 72.245 1.00 17.07 20 ATOM 2000 CG1 VAL 208 -16.790 2.305 70.950 1.00 16.77 0ATOM 2001 CG2 VAL 208 -15.539 2.182 73.095 1.00 11.55 ATOM 2002 C VAL 208 -16.656 5.205 70.983 1.00 18.54 *ATOM 2003 0 VAL 208 -17.696 5.741 71.377 1.00 17.58 ATOM 2004 N TYR 209 -16.216 5.276 69.730 1.00 18.01 ATOM 2005 H TYR 209 -15.380 4.834 69.510 1.00 0.00 ATOM 2006 CA TYR. 209 -16.923 5.978 68.666 1.00 16.80 ATOM 2007 CE TYR 209 -15.953 6.871 67.888 1.00 15.72 ATOM 2008 CG TYR 209 -15.356 7.983 68.715 1.00 19.87 ATOM 2009 CD1 TYR 209 -15.781 9.298 68.551 1.00 22.52 ATOM 2010 CEl TYR 209 -15.260 10.324 69.329 1.00 24.59 ATOM 2011 CD2 TYR 209 -14.387 7.721 69.679 1.00 18.42 ATOM 2012 CE2 TYR 209 -13.860 8.741 70.462 1.00 21.29 ATOM 2013 C Z TYR 209 -14.302 10.037 70.282 1.00 23.10 ATOM 2014 OH TYR 209 -13.798 11.052 71.058 1.00 27.37 ATOM 2015 HH TYR 209 -14.236 11.878 70.826 1.00 0.00 ATOM 2016 c TYR 209 -17.522 4.945 67.719 1.00 14.63 ATOM 2017 0 TYR 209 -16.941 3.882 67.505 1.00 14.50 ATOM 2018 N HIS 210 -18.706 5.238 67.195 1.00 13.02 ATOM 2019 H HIS 210 -19.145 6.068 67.452 1.00 0.00 124 ATOM 2020 CA HIS 210 -19.378 4.345 66.259 1.00 12.53 ATOM 2021 CB HIS 210 -20.662 3.786 66.864 1.00 12.65 ATOM 2022 CG HIS 210 -20.459 3.040 68.144 1.00 16.12 ATOM 2023 CD2 HIS 210 -20.531 3.447 69.432 1.00 14.44 ATOM 2024 ND1 HIS 210 -20.151 1.697 68.182 1.00 14.83 ATOM 2025 HD1 HIS 210 -19.968 1.099 67.418 1.00 0.00 ATOM 2026 CEl HIS 210 -20.047 1.309 69.440 1.00 15.80 ATOM 2027 NE2 HIS 210 -20.271 2.352 70.217 1.00 14.45 ATOM 2028 HE2 HIS 210 -20.186 2.357 71.186 1.00 0.00 ATOM 2029 c HIS 210 -19.734 5.160 65.031 1.00 13.68 ATOM 2030 0 HIS 210 -20.289 6.249 65.161 1.00 15.52 ATOM 2031 N TYR 211 -19.363 4.664 63.853 1.00 13.00 ATOM 2032 H TYR 211 -18.867 3 .819 63.799 1.00 0.00 99ATOM 2033 CA TYR 211 -19.658 5.333 62.590 1.00 10.84 ATOM 2034 CB TYR 211 -18.379 5.684 61.835 1.00 10.80 ATOM 2035 CG TYR 211 -17.516 6.699 62 .535 1.00 12.06 ATOM 2036 CD1 TYR 211 -16.582 6.304 63 .492 1.00 13.54 ATOM 2037 CEl TYR 211 -15.788 7.231 64.144 1.00 15.10 ATOM 2038 CD2 TYR 211 -17.631 8.056 62.247 1.00 13.72 ATOM 2039 CE2 TYR 211 -16.835 8.997 62.896 1.00 13.35 ATOM 2040 CZ TYR 211 -15.919 8.575 63.843 1.00 15.06 ATOM 2041 OH TYR 211 -15.127 9.487 64.494 1.00 16.21 *.*ATOM 2042 HH TYR 211 -14.660 9.055 65.212 1.00 0.00 ATOM 2043 c TYR 211 -20.486 4.397 61.743 1.00 11.32 ATOM 2044 0 TYR 211 -20.200 3.199 61.667 1.00 11.69 **ATOM 2045 N LEU 212 -21.511 4.950 61.114 1.00 9.85 ATOM 2046 H LEU 212 -21.636 5.919 61.180 1.00 0.00 ATOM 2047 CA LEU 212 -22.415 4.194 60.266 1.00 11.52 ATOM 2048 CB LEU 212 -23.775 4.912 60.217 1.00 11.56 ATOM 2049 CG LEU 212 -25.035 4.391 59.503 1.00 15.30 ATOM 2050 CD1 LEU 212 -25.117 4.895 58.086 1.00 16.57 ATOM 2051 CD2 LETJ 212 -25.126 2.883 59.563 1.00 13.66 ATOM 2052 c LEU 212 -21.830 4.050 58.863 1.00 12.35 ATOM 2053 0 LEU 212 -21.269 4.996 58.319 1.00 11. 11 ATOM 2054 N ILE 213 -21.906 2.842 58.317 1.00 11.83 ATOM 2055 H ILE 213 -22.310 2.108 58.828 1.00 0.00 ATOM 2056 CA ILE 213 -21.431 2.564 56.968 1.00 11.63 ATOM 2057 CB ILE 213 -20.299 1.504 56.954 1.00 12.05 ATOM 2058 CG2 ILE 213 -19.934 1.142 55.505 1.00 9.05 125 fle.

a.

a a.

a a a..

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2059 CG1 ILE 2060 CD ILE 2061 c ILE 2062 0 ILE 2063 N SER 2064 H SER 2065 CA SER 2066 CB SER 2067 OG SER 2068 HG SER 2069 c SER 2070 0 SER 2071 N GLN 2072 H GLN 2073 CA GLN 2074 CB GLN 2075 CG GLN 2076 CD GLN 2077 OE1 GLN 2078 NE2 GLN 2079 HE21 GLN 2080 HE22 GLN 2081 c GLN 2082 0 GLN 2083 N ASP 2084 H ASP 2085 CA ASP 2086 CB ASP 2087 CG ASP 2088 ODi ASP 2089 0D2 ASP 2090 c ASP 2091 0 ASP 2092 N LYS 2093 H LYS 2094 CA LYS 2095 CS LYS 2096 CG LYS 2097 CD LYS 213 213 213 213 214 214 214 214 214 214 214 214 215 215 215 215 215 215 215 215 215 215 215 215 216 216 216 216 216 216 216 216 216 217 217 217 217 217 217 -19.070 2.022 57.704 1.00 10.26 -17.985 0.988 57.897 1.00 9.92 -22.626 1.997 56.209 1.00 12.13 -23.269 1.063 56.685 1.00 13.61 -22.970 2.592 55.073 1.00 12.35 -22.502 3.387 54.736 1.00 0.00 -24.084 2.091 54.279 1.30 16.58 -25.328 2.965 54.462 1.00 20.18 -25.052 4.321 54.167 1.00 28.58 -25.884 4.781 54.279 1.0 ^0 0.00 -23.683 2.063 52.817 1.00 17.82 -22.747 2.753 52.413 1.00 17.93 -24.331 1.218 52.028 1.00 20.77 -25.045 0.650 52.395 1.00 0.00 -23.995 1.175 50.620 1.00 25.66 -23.692 -0.247 50.140 1.00 28.54 -24.821 -1.247 50.204 1.00 32.61 -24.390 -2.603 49.665 1.00 34.57 a. a -24.663 -23 .684 -23 .457 -23 .416 -25.063 -26.257 -24.621 -23.650 -25.536 -24. 862 -23 .572 -23 .455 -22.670 -26.111 -25.818 -26.910 -27 .102 -27.538 -28.406 -27 .645 -27.269 -3.638 50.270 1.00 38.97 -2.599 48.539 1.00 32.79 -1.751 48.109 1.00 0.00 -3.468 48.179 1.00 0.00 1.853 49.784 1.00 26.76 1.704 50.042 1.00 27.55 2.676 48.840 1.00 27.69 2.786 48.753 1.20 0.00 3.407 47.977 1.00 28.52 4.672 47.417 1.00 27.76 4.381 46.642 1.00 26.36 3.317 46.003 1.00 26.80 5.242 46.654 1.00 26.55 2.558 46.851 1.00 30.65 1.367 46.745 1.00 29.83 3.196 46.001 1.00 35.42 4.124 46.214 1.00 0.00 2.543 44.857 1.00 38.73 3.540 44.074 1.00 42.89 4.721 43.478 1.00 48.87 5.752 44.537 1.00 53.40 126 ATOM 2098 CE LYS 217 -26.291 6.785 43.996 1.00 58.3:.

ATOM 2099 NZ LYS 217 -24.979 6.187 43.601 1.00 59.73 ATOM 2100 HZ1 LYS 217 -25.131 5.461 42.871 1.00 0.00 ATOM 2101 HZ2 LYS 217 -24.529 5.743 44.426 1.00 0.00 ATOM 2102 HZ3 LYS 217 -24.352 6.930 43.224 1.00 0.00 ATOM 2103 C LYS 217 -26.502 1.913 43.925 1.00 38.15 ATOM 2104 0 LYS 217 -26.749 0.865 43.328 1.00 40.41 ATOM 2105 N ALA 218 -25.340 2.552 43.814 1.00 35.55 ATOM 2106 H ALA 218 -25.215 3.381 44.311 1.00 0.00 ATOM 2107 CA ALA 218 -24.265 2.052 42.959 1.00 33.42 ATOM 2108 CB ALA 218 -23.274 3.168 42.659 1.00 33.11 ATOM 2109 C ALA 218 -23.535 0.850 43.563 1.00 31.29 ATOM 2110 0 ALA 218 -22.651 0.274 42.928 1.00 32.67 ATOM 2111 N GLY 219 -23.891 0.490 44.794 1.00 28.81 ATOM 2112 H GLY 219 -24.622 0.946 45.252 1.00 0.00 ATOM 2113 CA GLY 219 -23.253 -0.633 45.461 1.00 25.16 ATOM 2114 C GLY 219 -21.997 -0.266 46.235 1.00 21.96 ***ATOM 2115 0 GLY 219 -21.363 -1.132 46.841 1.00 21.31 ATOM 2116 N LYS 220 -21.642 1.015 46.223 1.00 18.93 ATOM 2117 H LYS 220 -22.183 1.645 45.717 1.00 0.00 ATOM 2118 CA LYS 220 -20.465 1.499 46.929 1.00 17.78 ATOM 2119 CB LYS 220 -19.940 2.767 46.266 1.00 20.25 ***ATOM 2120 CG LYS 220 -19.307 2.495 44.913 1.00 24.18 ATOM 2121 CD LYS 220 -18.898 3.771 44.211 1.00 31.09 ATOM 2112 2 CE LYS 220 -18.088 3.470 42.960 1.00 34.60 ATOM 2123 NZ LYS 220 -18.821 2.569 42.026 1.00 37.47 :ATOM 2124 HZI LYS 220 -19.718 3 .013 41.752 1.00 0.00 ATOM 2125 HZ2 LYS 220 -19.017 1.663 42.495 1.00 0.00 ATOM 2126 HZ3 LYS 22 0 -18.261 2.395 41.170 1.00 0.00 ATOM 2:27 C LYS 220 -20.746 1.743 48.407 1.00 16.48 ATOM 2128 0 LYS 220 -21.865 2.094 48.780 1.00 17.93 ATOM 2129 N TYR 221 -19.728 1.535 49.236 1.00 12.90 ATOM 2130 H TRip 221 -18.873 1.259 48.858 1.00 0.00 ATOM 2131 CA TYR 221 -19.837 1.709 50.680 1.00 13.00 ATOM 2132 CB TYR 221 -19.086 0.593 51.414 1.00 14.73 ATOM 2133 CG TYR 221 -19.541 -0.805 51.080 1.00 14.94 ATOM 2134 CD1 TYR 221 -19.019 -1.481 49 .982 1.00 14.31 ATOM 2135 CEl TYR 221 -19.413 -2.779 49.682 1.00 17.85 ATOM 2136 C02 TYR 221 -20.479 -1.464 51.876 1.00 18.01 127 0000 4 S S 0@ @000 0 0000 00 *0 S

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0*@S 0 0*50 0@ 50 0 O550 0 0 *00500 0 0 *00000 0

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1 5 ATOM

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20 ATOM

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2137 CE2 TYR 2138 CZ TYR 2139 OH TYR 2140 HH TYR 2141 C TYR 2142 0 TYR 2143 N CYS 2144 H CYS 2145 CA CYS 2146 CB CYS 2147 SG CYS 2148 C CYS 2149 0 CYS 2150 N ILE 2151 H ILE 2152 CA ILE 2153 CB ILE 2154 CG2 ILE 2155 CG1 ILE 2156 CD ILE 2157 C ILE 2158 0 ILE 2159 N PRO 2160 CD PRO 2161 CA PRO 2162 CB PRO 2163 CG PRO 2164 c PRO 2165 0 PRO 2166 N GLU 2167 H GLU 2168 CA GLU 2169 CB GLU 2 170 CG GLU 2171 CD GLU 2172 OE1 GLU 2173 0E2 GLU 2174 c GLU 2175 0 GLU 221 221 221 221 221 221 222 222 222 222 222 222 222 223 223 223 223 223 223 223 223 223 224 224 224 224 224 224 224 225 225 225 225 225 225 225 225 225 225 -20.881 -20.339 -20. 710 -21. 440 -19.239 -18.268 -19.792 -20.597 -19.270 -19.460 -21. 164 -19.924 -21.011 -19.194 -18.278 -19.709 -18.542 -19.073 -17.712 -16.409 -20.409 -19.883 -21.627 -22.436 -22.313 -23.430 -23.798 -21.418 -20.737 -21.406 -21.973 -20.611 -20.880 -22.332 -22.586 -22.900 -22.472 -19.109 -18.297 -2 .769 51.583 1.00 19.06 -3.418 50.483 1.00 18.46 -4.712 50.187 1.00 21.74 -4.960 50.769 1.00 0.00 3.026 51.127 1.00 13.74 3.505 50.537 1.00 13.39 3.588 52.196 1.00 12.18 3.211 52.622 1.00 0.00 4.832 52.738 1.00 12.71 5.988 51.746 1.00 12.80 6.569 51.564 1.00 18.19 5.225 54.042 1.00 11.87 4.751 54.382 1.00 13.51 6.019 54.814 1.00 11.88 6.244 54.535 1.00 0.00 6.588 56.049 1.00 11.29 7.030 56.971 1.00 10.12 7.735 58.217 1.00 9.33 5.801 57.366 1.00 10.22 6.116 58.065 1.00 12.74 7.805 55.418 1.00 13.19 8.380 54.461 1.00 14.19 8.158 55.864 1.00 13.86 7.580 56.951 1.00 15.81 9.314 55.269 1.00 14.75 9.593 56.271 1.00 15.29 8.225 56.718 1.00 16.55 10.538 55.052 1.00 13.87 10.999 55.972 1.00 14.06 11.024 53.812 1.00 16.66 10.588 53.143 1.00 0.00 12.184 53 .399 1.00 18.98 13.377 54.321 1.00 23.00 13.822 54.340 1.00 31.63 14.925 55.345 1.00 38.26 14.610 56.514 1.00 44.60 16.111 54.965 1.00 44.04 11.901 53.325 1.00 17.01 12.827 53.247 1.00 17.14 128

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1 5 ATOM

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25 ATOM

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2176 N GLY 2177 H GLY 2178 CA GLY 2179 C GLY 2180 0 GLY 2181 N THR 2182 H THR 2183 CA THR 2184 CB THR 2185 OGi THR 2186 HG1 TER 2187 CG2 THR 2188 C THR 2189 0 THR 2190 N LYS 2191 H LYS 2192 CA LYS 2193 CB LYS 2194 CG LYS 2195 CD LYS 2196 CE LYS 2197 NZ LYS 2198 HZ1 LYS 2199 HZ2 LYS 2200 HZ3 LYS 2201 C LYS 2202 0 LYS 2203 N PHE 2204 H PHE 2205 CA PHE 2206 CB PHE 2207 CG PHE 2208 CD1 PHE 2209 CD2 PHE 2210 CE1 PHE 2211 CE2 PHE 2212 CZ PHE 2213 C PHE .2214 0 PHE 226 226 226 226 226 227 227 227 227 227 227 227 227 227 228 228 228 228 228 228 228 228 228 228 228 228 228 229 229 229 229 229 229 229 229 229 229 229 229 -18.745 -19 .411 -17.347 -16.950 -17.741 -15 .713 -15.132 -15 .161 -13 .660 -12 .995 -12.972 -13 .004 -15.907 -16.348 -16.064 -15.734 -16.751 -17 .773 -18.879 -19 .925 -21.091 -21.680 -20.949 -22.012 -22.481 -15 .765 -14.730 -16.093 -16.935 -15.256 -14.666 -13 .962 -14.669 -12.596 -14.026 -11.944 -12.657 -16 .083 -17.298 10.623 53.308 1.00 14.45 9.908 53.330 1.00 0.00 10.255 53.244 1.00 11.18 9.659 51.910 1.00 10.31 9.618 50.969 1.00 9.78 9.189 51.843 1.00 12.43 9.231 52.635 1.00 0.00 8.580 50.642 1.00 13.92 8.259 50.845 1.00 13.92 9.405 51.387 1.00 14.17 10.110 50.731 1.00 0.00 7.903 49.531 1.00 13.18 7.288 50.339 1.00 13.19 6.600 51.256 1.00 15.61 6.968 49.061 1.00 12.19 7.560 48.345 1.00 0.00 5.746 48.676 1.00 14.24 6.035 47.582 1.00 17.80 6.939 48.084 1.00 18.53 7.208 47.046 1.00 24.24 7.919 47.693 1.00 25.57 7.085 48.782 1.00 26.31 6.908 49.499 1.00 0.00 6.178 48.395 1.00 0.00 7.585 49.217 1.00 0.00 4.663 48.258 1.00 14.50 4.948 47.650 1.00 13.50 3.424 48.612 1.00 11.73 3.271 49.091 1.00 0.00 2.266 48.331 1.00 11.12 1.726 49.633 1.00 10.16 2.761 50.453 1.00 10.70 3.545 51.364 1.00 10.54 2.969 50.309 1.00 9.61 4.516 52.112 1.00 9.20 3.940 51.057 1.00 9.06 4.715 51.959 1.00 9.11 1.168 47.688 1.00 12.28 1.086 47 .908 1.00 10.19 129

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15 ATOM

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25 ATOM

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2215 N ASP 2216 H ASP 2217 CA ASP 2218 CB ASP 2219 CG ASP 2220 ODI ASP 2221 OD2 ASP 2222 C ASP 2223 0 ASP 2224 N THR 2225 H THR 2226 CA THR 2227 CB THR 2228 OGI THR 2229 HG1 THR 2230 CG2 THR 2231 C THR 2232 0 THR 2233 N LEU 2234 H LEU 2235 CA LEU 2236 C3 LEU 2237 CG LEU 2238 CD1 LEU 2239 CD2 LEU 2240 C LEU 2241 0 LEU 2242 N TRP 2243 H TRP 2244 CA TRP 2245 CE TRP 2246' CG TRP 2247 CD2 TRP 2248 CE2 TRP 2249 CE3 TRP 2250 CDI TRP 2251 NEI TRP 2252 HEl TRP 2253 CZ2 TRP 230 230 230 230 230 230 230 230 230 231 231 231 231 231 231 231 231 231 232 232 232 232 232 232 232 232 232 233 233 233 233 233 233 233 233 233 233 233 233 -15.426 0.325 46.898 1.20 10.90 -14.463 0.469 46.747 1.0 0.00 -16.105 -0.786 46.233 1.00 12.50 -15.298 -1.275 45.027 1.00 11.22 -15.537 -0.441 43.784 1.00 14.98 -14.994 -0.805 42.725 1.00 16.87 -16.267 0.569 43.852 1.00 18.88 -16.353 -1.947 47.185 1.00 10.65 -17.276 -2.736 46.984 1.00 11.11 -15.529 -2.047 48.224 1.00 11.48 -14.831 -1.374 48.373 1.00 0.00 -15.664 -3.120 49.197 1.00 7.69 -14.672 -4.283 48.916 1.00 7.51 -13.326 -3.812 49.047 1.00 6.84 -13.152 -3.283 48.249 1.20 0.00 -14.867 -4.851 47.514 1.0 9.18 -15.383 -2.611 50.601 1.00 8.28 -14.786 -1.549 50.787 1.00 6.01 -15.803 -3.394 51.587 1.00 11.12 -16.301 -4.202 51.349 1. 30 0.00 -15.576 -3.069 52.991 1.00 11.15 -16.452 -3.943 53.890 1.00 10.62 -17.944 -3.612 53.890 1.00 10.59 -18.702 -4.656 54.692 1. 00 9.60 -18.163 -2.225 54.474 1 .0 9.95 -14.106 -3.254 53.355 1 .0 10.18 -13.591 -2.556 54.224 1.20 10.71 -13.433 -4.188 52.682 1.00 7.94 -13.899 -4.714 52.004 1.0 0.00 -12.019 -4.454 52.930 1.00 7.29 -11.547 -5.644 52.082 1.00 6.24 -10.206 -6.191 52.486 1 .00 8.76 -8.918 -5.653 52.152 1.00 10.99 -7.949 -6.473 52.772 1.00 8.57 -8.487 -4.551 51.394 1.00 10.97 -9.971 -7.291 53 .265 1.00 9.24 -8.619 -7.463 53.441 1.00 9.83 -8.218 -8.194 53 .968 1.00 0.00 -6.577 -6.229 52 .658 1.00 9.97 130 a a ATOM 2254 CZ3 TRP ATOM 2255 CH2 TRP ATOM 2256 C TRP ATOM 2257 0 TRP ATOM 2258 N GLN ATOM 2259 H GLN ATOM 2260 CA GLN ATOM 2261 CB GLN ATOM 2262 CG GLN 1 0 ATOM 2263 CD GLN ATOM 2264 OE1 GLN ATOM 2265 NE2 GLN ATOM 2266 HE21 GLN ATOM 2267 HE22 GLN 1 5 ATOM 2268 C GLN ATOM 2269 0 GLN ATOM 2270 N LEU ATOM 2271 H LEU ATOM 2272 CA LEU ATOM 2273 CB LEU ATOM 2274 CG LEU ATOM 2275 CD1 LEU ATOM 2276 CD2 LEU ATOM 2277 c LEU ATOM 2278 0 LEU ATOM 2279 N VAL ATOM 2280 H VAL ATOM 2281 CA VAL ATOM 2282 CB VAL ATOM 2283 CG1 VAL ATOM 2284 CG2 VAL ATOM 2285 c VAL ATOM 2286 0 VAL ATOM 2287 N GLU ATOM 2288 H GLU ATOM 2289 CA GLU ATOM 2290 CB GLU ATOM 2291 CG GLU ATOM 2292 CD GLU 233 233 233 233 234 234 234 234 234 234 234 234 234 234 234 234 235 235 235 235 235 235 235 235 235 236 236 236 236 236 236 236 236 237 237 237 237 237 237 -7.120 -4.307 51.281 1.00 9.13 -6.183 -5.144 51.913 1.00 11.33 -11.197 -3.207 52.599 1.00 7.04 -10.319 -2.799 53.370 1.00 7.78 -11.503 -2.593 51.461 1.00 8.41 -12.219 -2.958 50.896 1.00 0.00 -10.803 -1.388 51.014 1.00 9.39 -11.165 -1.071 49.562 1.00 8.16 -10.565 -2.062 48.559 1.00 10.01 -11.154 -1.939 47.158 1.00 12.43 -12.366 -2.054 46.969 1.00 11.45 -10.292 -1.740 46.168 1.00 12.16 -9.333 -1.691 46.378 1.00 0.00 -10.642 -1.644 45.264 1.00 0.00 -11.057 -0.179 51.916 1.00 8.34 -10.160 0.632 52.140 1.00 11.19 -12.275 -0.065 52.434 1.00 9.44 -12.961 -0.717 52.193 1.00 0.00 -12.644 1.025 53.336 1.00 9.31 -14.137 0.914 53.705 1.00 10.64 -14.799 1.893 54.690 1.00 8.65 -16.276 2.014 54.359 1.00 12.30 -14.606 1.444 56.139 1.00 8.88 -11.768 0.979 54.592 1.00 10.98 -11.118 1.964 54.949 1.00 10.19 -11.726 -0.185 55.232 1.00 11.09 -12.243 -0.941 54.873 1.00 0.00 -10.941 -0.372 56.446 1.00 13.11 -11.160 -1.792 57.035 1.00 13.64 -10.210 -2.052 58.198 1.00 9.34 -12.606 -1.937 57.497 1.00 9.82 -9.460 -0.122 56.202 1.00 12.74 -8.814 0.617 56.947 1.00 12.87 -8.936 -0.692 55.124 1.00 11.87 -9.506 -1.255 54.555 1.00 0.00 -7.526 -0.530 54.810 1.00 14.06 -7.131 -1.443 53.654 1.00 18.30 -6.010 -2.409 54.009 1.00 27.57 -6.318 -3.258 55.236 1.00 33.91 131 0.0.

00

ATOM

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1 0 ATOM

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1 5 ATOM

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25 ATOM

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2293 OE1 GU 2294 0E2 GU 2295 C GLU 2296 0 GLU 2297 N TYR 2298 H TYR 2299 CA TYR 2300 CB TYR 2301 CG TYR 2302 CD1 TYR 2303 CEI TYR 2304 CD2 TYR 2305 CE2 TYR 2306 CZ TYR 2307 OH TYR 1308 HH TYR 2309 C TYR 2310 0 TYR 2311 N LEU 2312 H LEU 2313 CA LEU 2314 CB LEU 2315 CG LEU 2316 CD1 LEU Z217 CD2 LEU 2318 C LEU 2319 0 LEU 2320 N LYS 2321 H LYS 2322 CA LYS 2323 CB LYS 2324 CG LYS 2325 CD LYS 2.326 CE LYS 2327 NZ LYS 2328 HZ1 LYS 2329 HZ2 LYS 2330 HZ3 LYS 2331 C LYS 237 237 237 237 238 238 238 238 238 238 238 238 238 238 238 238 238 238 239 239 239 239 239 239 239 239 239 240 240 240 240 240 240 240 240 240 240 240 240 -7.140 -6.046 -8.048 -8.918 -7.811 -8.917 -8.736 -7.971 -7.866 -9.385 -9.286 -8.530 -8.461 -7.934 -7.787 -6.896 -8.739 -9.406 -8.844 -10.225 -11. 369 -12.723 -11.208 -7.713 -7.609 -6.881 -7.069 -5.721 -5.258 -6.069 0.911 54.513 1.00 11.41 1.347 54.862 1.00 13.53 1.651 53.887 1.00 10.99 1.250 53.660 1.00 0.00 3.051 53.547 1.00 10.24 3.539 52.616 1.00 8.37 4.938 52.070 1.00 9.95 5.165 50.923 1.00 11.03 6.436 50.371 1.00 11.61 6.023 52.655 1.00 9.61 7.295 52.109 1.00 13.06 7.494 50.969 1.00 12.38 8.750 50.423 1.00 15.47 8.739 49.623 1.00 0.00 3.898 54.819 1.00 12.10 4.730 55.014 1.00 10.77 3.636 55.709 1.00 12.47 2.937 55.527 1.00 0.00 4.371 56.960 1.00 12.96 4.161 57.581 1.00 11.26 4.619 56.659 1.00 14.61 4.368 57.306 1.00 11.36 6.100 56.303 1.00 15.59 4.045 57.938 1.00 15.09 4.644 59.014 1.00 15.00 3.073 57.572 1.00 15.14 2.565 56.760 1.00 0.00 2.713 58.380 1.00 17.35 1.284 58.095 1.00 15.90 0.192 58.749 1.00 19.37 -5.411 -3.405 56.082 1.00 36.05 -7.452 -3.781 55.356 1.00 36.98 -5.352 -1.147 58.604 1.00 23.39 -6.141 -2.282 59.234 1.00 26.87 -5.449 -3.592 59.076 1.00 27.64 -4.528 -3.564 59.561 1.00 0.00 -5.303 -3.797 58.066 1.00 0.00 -6.056 -4.328 59.485 1.00 0.00 -4.602 3.674 57.988 1.00 18.17 132 a

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15 ATOM

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ATOM

2332 0 LYS 2333 N LEU 2334 H LEU 2335 CA LEU 2336 CB LEU 2337 CG LEU 2338 CD1 LEU 2339 CD2 LEU 2340 C LEU 2342. 0 LEU 2342 N LYS 2343 H LYS 2344 CA LYS 2345 CB LYS 2346 CG LYS 2347 CD LYS 2348 CE LYS 2349 NZ LYS 2350 HZ1 LYS 2351 HZ2 LYS 2352 HZ3 LYS 2353 C LYS 2354 0 LYS 2355 N ALA 2356 H ALA 2357 CA ALA 2358 CE ALA 2359 C ALA 2360 0 ALA 2361 N ASP 2362 H ASP 2363 CA ASP 2364 CB ASP 2365 CG ASP 2366 ODI ASP 2367 0D2 ASP 2368 c ASP 2369 0 ASP 2370 N GLY 240 241 241 241 241 241 241 241 241 241 242 242 242 242 -42 242 242 242 242 242 242 242 242 243 2 43 274 3 '43 24 3 24 3 244 244 244 244 244 244 244 244 244 245 -3 .741 -4.624 -5.346 -3 .609 -3.499 -3.315 -3 .353 -2 .008 -3.906 -2 .997 -5.176 -5 .879 -5.581 -5.570 -6.401 -6.085 -4.720 -4.450 -4 .507 -5 .152 -3 .496 -6.955 -7 .853 -7 .110 -6.329 -8.362 -8.233 -9.540 -10.632 -9.332 -8.459 -10.359 -10.481 -11.295 -12.087 -11.139 -11.723 -12.786 -11.687 4.005 58.797 1.00 20.88 4.119 56.737 1.00 19.69 3.850 56.132 1.00 0.00 5.034 56.235 1.00 24.27 4.927 54.708 1.00 27.48 3.550 54.060 1.00 32.84 3.698 52.541 1.00 33.90 2.909 54.505 1.00 33.04 6.483 56.615 1.00 23.86 7.237 56.962 1.00 25.78 6.870 56.544 1.00 23.81 6.232 56.282 1.00 0.00 8.237 56.851 1.00 22.58 9.074 55.565 1.00 25.37 8.478 54.432 1.00 27.76 9.108 53.085 1.00 30.37 8.701 52.554 1.00 28.46 9.342 51.238 1.00 27.65 10.369 51.346 1.00 0.00 9.021 50.544 1.00 0.00 9.081 50.914 1.00 0.00 8.287 57.512 1.00 19.10 7.535 57.142 1.00 17.80 9.197 58.473 1.00 18.84 9.765 58.680 1.00 0.00 9.362 59.214 1.00 17.03 10.489 60.240 1.00 14.93 9.620 58.285 1.00 16.79 9.098 58.503 1.00 15.85 10.486 57.295 1.00 17.15 10.915 57.232 1.00 0.00 10.796 56.304 1.00 18.82 9.599 55.347 1.00 18.91 9.904 54.113 1.00 21.74 9.030 53.712 1.00 23.51 10.998 53.533 1.00 25.93 11.169 56.923 1.00 19.28 10.734 56.461 1.00 17.04 11.994 57.963 1.00 18.87 133

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2371 H GLY 2372 CA GLY 2373 C GLY 2374 0 GLY 2375 N LEU 2376 H LEU 2377 CA LEU 2378 CB LEU 2379 CG LEU 2380 CD1 LEU 2381 CD2 LEU 2382 C LEU 2383 0 LEU 2384 N ILE 2385 H ILE 2386 CA ILE 2387 CB ILE 2388 CG2 ILE 2389 CG1 ILE 2390 CD ILE 2391 C ILE 2392 0 ILE 2393 N TYR 2394 H TYR 2395 CA TYR 2396 CB TYR 2397 CG TYR 2398 CDl TYR 2399 CE! TYR 2400 CD2 TYR 2401 CE2 TYR 2402 CZ TYR 2403 OH TYR 2404 HH TYR 2405 c TYR 2406 0 TYR 2407 N CYS 2408 H CYS 2409 CA CYS 245 245 245 245 246 246 246 246 246 246 246 246 246 247 247 247 247 247 247 247 247 247 248 248 2 48 248 248 248 248 248 248 248 248 248 248 248 249 249 249 -10.837 -12.920 -13 .123 -13.863 -12 .503 -11.973 -12. 623 -12.066 -12.647 -11.849 -14.104 -11.866 -10.921 -12 .253 -13.020 -11.636 -12 .424 -12.209 -12.020 -12.501 -10.163 -9.340 -9 .840 -10.512 -8.484 -8.174 -6.704 -6.212 -4.861 -5.810 -4.457 -3.992 -2.664 -2.203 -8.463 -9.506 -7.304 -6 .477 -7.252 12.330 58.306 1.00 0.00 12.402 58.613 1.00 18.84 11.779 59.982 1.00 18.77 12.319 60.804 1.00 18.51 10.625 60.218 1.00 18.35 10.209 59.505 1.00 0.00 9.949 61.506 1.00 18.30 8.519 61.442 1.00 17.23 7.431 60.534 1.00 17.12 6.151 60.746 1.00 18.63 7.186 60.834 1.00 15.56 10.707 62.591 1.00 18.47 11.448 62.307 1.00 17.84 10.453 63.8371 1.00 17.52 9.857 63.945 1.00 0.00 11.072 65.005 1.00 18.73 10.694 66.302 1.00 19.74 9.225 66.664 1.00 17.58 11.599 67.463 1.00 22.31 13.023 67.320 1.00 25.66 10.651 65.129 1.00 20.39 11.381 65.680 1.00 20.44 9.475 64.598 1.00 20.63 8.919 64.159 1.00 0.00 8.937 64.631 1.00 21.07 8.391 66.030 1.00 20.66 8.168 66.310 1.00 21.55 6.894 66.590 1.00 23.90 6.691 66.884 1.00 27.45 9.235 66.327 1.00 24.95 9.045 66.622 1.00 26.89 7.773 66.900 1.00 27.31 7.588 67.209 1.00 32.39 8.432 67.197 1.00 0.00 7.806 63.602 1.00 21.64 7.223 63.307 1.00 22.45 7.510 63.025 1.00 21.61 7.958 63.280 1.00 0.00 6.444 62.035 1.00 22.88 134 ATOM 2410 CB CYS 249 -6.102 6.649 61.042 1.00 25.15 ATOM 2411 SG CYS 249 -4.471 6.722 61.779 1.00 42.25 ATOM 2412 C CYS 249 -7.189 5.068 62.692 1.00 21.47 ATOM 2413 0 CYS 249 -6.787 4.929 63.853 1.00 20.61 ATOM 2414 N LEU 250 -7.642 4.065 61.952 1.00 20.77 ATOM 2415 H LEU 250 -7.945 4.257 61.037 1.00 0.00 ATOM 2416 CA LEU 250 -7.674 2.687 62.425 1.00 20.19 ATOM 2417 CB LET) 250 -8.416 1.820 61.405 1.00 18.49 ATOM 2418 CG LET) 250 -9.944 1.724 61.463 1.00 17.48 ATOM 2419 CD1 LET) 250 -10.596 2.988 61.983 1.00 17.55 ATOM 2420 CD2 LET) 250 -10.467 1.353 60.095 1.00 11.95 ATOM 2421 C LET) 250 -6.274 2.142 62.662 1.00 21.59 .*ATOM 2422 0 LET) 250 -5.389 2.319 61.829 1.00 22.32 ATOM 2423 N LYS 251 -6.077 1.480 63.797 1.00 23.42 1 5 ATOM 2424 H LYS 251 -6.834 1.343 64.404 1.00 0.00 ATOM 2425 CA LYS 251 -4.776 0.913 64.136 1.00 27.72 :::ATOM 2426 CB LYS 251 -4.191 1.594 65.381 1.00 27.91 ATOM 2427 CG LYS 251 -3.938 3.085 65.239 1.00 29.20 ATOM 2428 CD LYS 251 -2.882 3.372 64.197 1.00 30.93 20 ATOM 2429 CE LYS 251 -2.677 4.859 64.038 1.00 33 ATOM 2430 NZ LYS 251 -1.669 5.159 62.987 1.00 38.98 ATOM 2431 HZ1 LYS 2151 -1.976 4.774 62.070 1.00 0.00 ATOM 2432 HZ2 LYS 251 -0.753 4.744 63.253 1.00 0.00 ATOM 2433 HZ3 LYS 251 -1.561 6.191 62.908 1.00 0.00 25 ATOM 2434 C LYS 251 -4.837 -0.603 64.353 1.00 31.01 ATOM 2435 0 LYS 2151 -4.768 -1.385 63.401 1.00 34.63 ATOM 2436 N GLU 252 -4.991 -1.013 65.606 1.00 31.53 ATOM 2437 H GLU 252 -5.146 -0.377 66.329 1.00 0.00 ATOM 2438 CA GLU 252 -5.036 -2.426 65.952 1.00 31.94 ATOM 2439 CB GLU 252 -4.535 -2.629 67.383 1.00 36.37 ATOM 2440 CG GLU 252 -3.113 -2.136 67.621 1.00 47.65 ATOM 2 441 CD GLU 252 -2.878 -1.678 69.053 1.00 53.28 ATOM 2442 DEl GLU 252 -2.807 -0.447 69.277 1.00 56.81 ATOM 2443 0E2 GLU 252 -2.770 -2.542 69.952 1.00 56.39 ATOM 2444 c GLU 252 -6.440 -2.993 65.817 1.00 30.12 ATOM 2445 0 GLU 252 -7.419 -2.361 66.213 1.00 29.12 ATOM 2446 N ALA 253 -6.527 -4.182 65.237 1.00 26.83 ATOM 2447 H ALA 253 -5.716 -4.627 64.930 1.00 0.00 ATOM 2448 CA ALA 253 -7.795 -4.853 65.063 1.00 26.20 .135 ATOM 2449 CB ALA 253 ATOM 449 B AL 253 -7.698 -5.868 63.944 1.00 25.70 a.

1 5 25 ATOM 2450 ATOM 2451 ATOM 2452 ATOM 2453 ATOM 2454 ATOM 2455 ATOM 2456 ATOM 2457 ATOM 2458 ATOM 2459 ATOM 2460 ATOM 2461 ATOM 2462 ATOM 2463 ATOM 2464 ATOM 2465 ATOM 2466 ATOM 2467 ATOM 2468 ATOM 2469 ATOM 2470 ATOM 2471 ATOM 2472 ATOM 2473 ATOM 2474 ATOM 2475 ATOM 2476 ATOM 2477 ATOM 2478 ATOM 2479 ATOM 2480 ATOM 2481 ATOM 2482 ATOM 2483 ATOM 2484 ATOM 2485

C

0

N

H

CA

CB

SG

C

0

N

CD

CA

CB

CG

C

0

N

H

CA

CB

CG

ODi ND2 HD21 HD22

C

0

OT

CB

CG

ODi ND2 HD21 HD22

C

0 HT1 HT2 ALA 253 ALA 253 CYS 254 CYS 254 CYS 254 CYS 254 CYS 254 CYS 254 CYS 254 PRO 255 PRO 255 PRO 255 PRO 255 PRO 255 PRO 255 PRO 255 AiSN 256 ASN 256 PSN 256 PSN 256 ASN 256 PSN 256 PSN 256 PSN 256 ASN 256 A.SN 256 ASN 256 ASN 256 ASN 301 PSN 301 PSN 301 PSN 301 ASN 301 PSN 301 PkSN 301 ASN 301 PSN 301 ASN 301 -8.149 -7.276 -9.414 -10. 046 -9.907 -11.087 -11. 787 -10. 372 -11. 391 -9 .584 -8.346 -9.865 -8.780 -7 .643 -11.258 -12.027 -11.549 -10.862 -12.825 -12.631 -11.494 -10.354 -11.798 -12.721 -11.107 -13.545 -12.888 -14.776 -31.365 -32.706 -33.338 -33.146 -32.620 -34.026 -30.146 -30.767 -31.950 -30.386 -5.554 -6.096 -5.473 -4.955 -6.143 -5.361 -6.015 -7.475 -7.528 -8.545 -8.542 -9.900 -10.738 -9 .774 -10.437 -9.807 -11.612 -12.052 -12.314 -13.804 -14 .430 -14.507 -14.874 -14.706 -15.313 -12.159 -12.281 -11.934 5.229 5.204 4.151 6.360 7.179 6.336 4.272 3.599 2 .747 2.096 66.361 67.036 66.746 66.206 67.941 68 .533 70 .077 67.358 66.674 67.554 68.352 67.058 67 .733 67. 847 67.368 68.088 66.813 66 .277 66.965 66 .654 67 .455 66.987 68.666 68.970 69 .188 68 .308 69.365 68.282 63 .299 64.007 64.119 64.490 64.396 64.926 65.265 66.093 64.009 64.004 1.00 1 .00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1 .00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1 .00 1.00 28.42 28.38 31.05 0.00 32.95 34.98 32 .47 35.53 33.47 40.79 42 .81 45.35 46.01 43 .91 48.63 50.93 52 .77 0.00 56.77 56.87 58.22 58.21 60.09 0.00 0.00 59.22 60.95 62.08 56 .01 56.26 54.90 56.88 0.00 0 .00 56.46 57.32 0.00 0 .00 a.

*a.aa.

a

ATOM

ATOM

2486 2487 136 ATOM 2488 N ASN 301 ATM 48 N AS 31 -31.028 2.767 63 .513 1.00 55.62 15 20 ATOM 2489 ATOM 2490 ATOM 2491 ATOM 2492 ATOM 2493 ATOM 2494 ATOM 2495 ATOM 2496 ATOM 2497 ATOM 2498 ATOM 2499 ATOM 2500 ATOM 2501 ATOM 2502 ATOM 2503 ATOM 2504 ATOM 2505 ATOM 2506 ATOM 2507 ATOM 2508 ATOM 2509 ATOM 2510 HT3 ASN 301 CA ASN 301 N GLN 302 H GLN 302 CA GLN 302 CB GLN 302 CG GLN 302 CD GLN 302 OE1 GLN 302 NE2 GLN 302 HE21 GLN 302 HiE22 GLN 302 C GLN 302 O GLN 302 N LEU 303 H LEU 303 CA LEU 303 CB LEU 303 CG LEU 303 CD1 LEU 303 CD2 LEU 303 C LEU 303 O LEU 303 N PTY 304 H PTY 304 CA PTY 304 CB PTY 304 CG PTY 304 CD1 PTY 304 CEl PTY 304 CD2 PTY 304 CE2 PTY 304 CZ PTY 304 OH PTY 304 OR1 PTY 304 0R2 PTY 304 0R3 PTY 304 PR PTY 304 -31.104 2.517 -30.427 4.112 -29.220 5.167 -28.777 5.736 -28.849 5.397 -28.061 4.185 -28.174 3.927 -29.560 3.475 -30.386 4.280 -29.825 2.182 -29.131 1.575 -30.732 1.904 -27.998 6.670 -28.185 7.614 -27.061 6.677 -26.909 5.925 -26.165 7.802 -25.966 7.986 -27.251 7.951 -26.952 7.491 -27.926 9.316 -24.824 7.489 -23.917 6.942 -24.712 7.799 -25.443 8.263 -23.481 7.545 -23.774 6.882 -24.310 5.478 -23.459 4.375 -23.950 3.078 -25.662 5.253 -26.160 3.971 -25.305 2.889 -25.840 1.637 -26.848 1.189 -24.474 1.199 -25.836 -0.551 -25.659 0.847 62 .501 63 .774 65 .602 64.935 66.995 67.520 69 .017 69.421 69 .859 69.280 68.950 6 9 5 12 67.089 66 .314 68 .034 68.633 68.260 69 .764 70.594 72 .007 70.572 67 .595 68.228 66.309 65 .853 65 .572 64 .224 64.358 64.296 64 .462 64.580 64 .743 64 .687 64 .857 66.998 66.960 65 .882 66.222 1.00 0.00 1.00 56.70 1.00 55.38 1.00 0.00 1.00 52.01 1.00 54.35 1.00 56.79 1.00 60.50 1.00 63.09 1.00 60.40 1.00 0.00 1.00 0.00 1.00 47.72 1.00 46.40 1.00 43.29 1.00 0.00 1.00 36.89 1.00 38.96 1.00 42.01 1.00 41.24 1.00 43.88 1.00 31.37 1.00 31.51 1.00 25.51 1.00 0.00 1.00 22.04 1.00 18.08 1.00 16.80 1.00 15.50 1.00 17.12 1.00 18.22 1.00 18.21 1.00 16.53 1.00 15.66 1.00 17.78 1.00 13 .33 1.00 19.12 1.00 16.13

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2511 2512 2513 2514 2515 2516 2517 2518 2519 2520 2521 2522 2523 2524 2525 2526 137 ATOM 2527 C PTY 304 -22.717 8.839 65.375 1.00 20.65

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 0 ATOM

ATOM

2528 0 PTY 2529 N ASN 2530 H ASN 2531 CA ASN 2532 CB ASN 2533 CG ASN 2534 ODI ASN 2535 ND2 ASN 2536 HD21 ASN 2537 HD22 ASN 4 4* 4**4 4 4*4*4* ATOM 2'538 ATOM 2539 ATOM 2540 1 5 ATOM 2541 ATOM 2542 ATOM 2543 ATOM 2544 ATOM 2545 20 ATOM 2546 ATOM 2547 ATOM 2548 ATOM 2549 ATOM 2550 25 ATOM 2551 ATOM 2552 ATOM 2553 ATOM 2554 ATOM 2555 ATOM 2556 ATOM 2557 ATOM 2558 ATOM 2559 ATOM 2560 ATOM 2561 ATOM 2562 ATOM 2563 ATOM 2564 ATOM 2565 C ASN O ASN N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU OE2 GLU C GLU 0 GLU N LEU H LEU CA LEU CB LEU CG LEU CDI LEU CD2 LEU C LEU O LEU N ASN H ASN CA ASN CB ASN CG ASN ODI ASN ND2 ASN 304 305 305 305 305 305 305 305 305 305 305 305 306 306 306 306 306 306 306 306 306 306 307 307 307 307 307 307 307 307 307 308 308 308 308 308 308 308 -23.313 -21.396 -21.009 -20.545 -19.157 -19.197 -19.003 -19.481 -19.675 -19.499 -20.452 -20.549 -20.295 -20.232 -20.191 -20.911 -22.411 -23.053 -22.761 -23.846 -18.729 -17.859 -18.469 -19.208 -17.118 -16.995 -17.056 -16.950 -15.921 -16.778 -17.632 -15.544 -14.946 -15.108 -13.848 -13.325 -13.764 -12.363 9.909 8.741 7.863 9.907 9.625 9.305 10.180 8.054 7.444 7.805 10.333 9.503 11.635 12.234 12.203 13.556 13.510 14.889 15.719 15.143 12.416 12.502 12.528 12.499 12.747 12.307 10.831 10.720 10.075 14.223 15.075 14.529 13.819 15.913 16.076 17.502 18.348 17.769 65.272 65.358 65.445 65.189 65.764 67.241 68.084 67.567 66.829 68.521 63.725 62.819 63 .506 64.271 62.165 62.093 62.344 62.283 63 .169 61.349 61.791 62.665 60.493 59.842 60.005 58.544 58.166 56.658 58.829 60.080 59.843 60.455 60.757 60.479 61.324 61.322 60.540 62.186 1.00 23.13 1.00 18.57 1.00 0.00 1.00 20.26 1.00 19.11 1.00 21.22 1.00 24.78 1.00 20.41 1.00 0.00 1.00 0.00 1.00 20.42 1.00 21.37 1.00 21.58 1.00 0.00 1.00 22.52 1.00 28.56 1.00 37.30 1.00 41.64 1.00 43.36 1.00 45.10 1.00 20.22 1.00 20.01 1.00 18.25 1.00 0.00 1.00 16.72 1.00 16.17 1.00 13.26 1.00 14.79 1.00 12.43 1.00 18.93 1.00 19.72 1.00 18.95 1.00 0.00 1.00 22.39 1.00 22.65 1.00 24.93 1.00 23.61 1.00 29.91 138 ATOM 2566 HD21 ASN 308 -12.039 17.026 62.740 1.00 0.00 ATOM 2567 HD22 ASN 308 -12.030 18.689 62.233 1.00 0.00 ATOM 2568 C ASN 308 -14.800 16.173 59.012 1.00 22.77 ATOM 2569 0 ASN 308 -13.728 15.821 58.519 1.00 22.81 ATOM 2570 N LEU 309 -15.770 16.733 58.305 1.00 25.79 ATOM 2571 H LEU 309 -16.614 16.937 58.764 1.00 0.00 ATOM 2572 CA LEU 309 -15.624 17.002 56.884 1.00 29.56 ATOM 2573 CB LEU 309 -16.937 17.546 56.316 1.00 30.40 ATOM 2574 CG LEU 309 -18.120 16.573 56.465 1.00 31.06 1 0 ATOM 2575 CDI LEU 309 -19.365 17.171 55.845 1.00 29.69 ATOM 2576 CD2 LEU 309 -17.802 15.229 55.814 1.00 28.45 ATOM 2577 C LEU 309 -14.433 17.879 56.496 1.00 32.74 ATOM 2578 0 LEU 309 -13.980 17.840 55.352 1.00 34.00 ATOM 2579 N GLY 310 -13.896 18.628 57.453 1.00 34.39 5 ATOM 2580 H GLY 310 -14.259 18.618 58.363 1.00 0.00 ATOM 2581 CA GLY 310 -12.749 19.471 57.166 1.00 37.43 ATOM 2582 C GLY 310 -11.451 18.694 56.967 1.00 40.37 ATOM 2583 o GLY 310 -10.494 19.212 56.382 1.00 42.20 ATOM 2584 N ARG 311 -11.411 17.454 57.453 1.00 39.39 ATOM 2585 H ARG 311 -12.204 17.096 57.902 1.00 0.00 ATOM 2586 CA ARG 311 -10.220 16.613 57.334 1.00 37.84 o, ATOM 2587 CB ARG 311 -9.912 15.938 58.673 1.00 38.89 ATOM 2588 CG ARG 311 -9.364 16.864 59.737 1.00 42.25 ATOM 2589 CD ARG 311 -9.096 16.101 61.022 1.00 47.16 25 ATOM 2590 NE ARG 311 -10.323 15.546 61.587 1.00 51.46 ATOM 2591 HE ARG 311 -11.178 15.829 61.204 1.00 0.00 ATOM 2592 CZ ARG 311 -10.364 14.671 62.588 1.00 53.11 ATOM 2593 NH1 ARG 311 -9.242 14.231 63.145 1.00 54.45 ATOM 2594 HH11 ARG 311 -8.350 14.554 62.828 1.00 0.00 ATOM 2595 HH12 ARG 311 -9.301 13.580 63.901 1.00 0.00 ATOM 2596 NH2 ARG 311 -11.535 14.255 63.054 1.00 54.64 ATOM 2597 HH21 ARG 311 -12.383 14.597 62.652 1.00 0.00 ATOM 2598 HH22 ARG 311 -11.568 13.601 63.810 1.00 0.00 ATOM 2599 C ARG 311 -10.306 15.545 56.246 1.00 35.04 ATOM 2600 o ARG 311 -9.479 14.632 56.201 1.00 35 .34 ATOM 2601 N ARG 312 -11.315 15.639 55.389 1.00 34.68 ATOM 2602 H ARG 312 -11.927 16.402 55.451 1.00 0.00 ATOM 2603 CA ARG 312 -11.484 14.668 54.316 1.00 34.78 ATOM 2604 CB ARG 312 -12.882 14.766 53.706 1.00 35.31 139

*SS*

S S S

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2605 2606 2607 2608 2609 2610 2611 2612 2613 2614 2615 2616 2617 2618 2619 2620 2621 2622 2623 2624 2625 2626 2627 2628 2629 2630 2631 2632 2633 2634 2635 2636 2637 2638 2639 2640 2641 2642 2643 CG ARG 312 CD ARG 312 NE ARG 312 HE ARG 312 CZ ARG 312 NH1 ARG 312 HH11 ARG 312 HH12 ARG 312 NHi2 ARG 312 HH21 ARG 312 HH22 ARG 312 C ARG 312 0 ARG 312 N GLU 313 H GLU 313 CA GLU 313 CB GLU 313 CG GLU 313 CD GLU 313 OE1 GLU 313 0E2 GLU 313 C GLU 313 0 GLU 313 N GLU 314 H GLU 314 CA GLU 314 CB GLU 314 CG GLU 314 CD GLU 314 OE1 GLU 314 0E2 GLU 314 C GLU 314 GLU 314 N PTY 315 H PTY 315 CA PTY 315 CB PTY 315 CG PTY 315 CD1 PTY 315 -13 .947 -15.085 -14.597 -13 .715 -15.268 -16.473 -16.899 -16.956 -14.721 -13 .804 -15.225 -10.449 -9 .953 -10.121 -10.548 -9 .169 -8.586 -7 .367 -6 .114 -5.282 -5.954 -9 .903 -10.973 -9.332 -8.466 -9.939 -9 .771 -10.165 -8 .965 -8.667 -8 .322 -9.363 -8.152 -10.249 -11.206 -9 .854 -10.482 -9 .678 -8.575 13.942 13 .646 12 .970 12.542 12.882 13 .423 13 .908 13 .348 12.271 11.879 12.194 14.829 15.929 13 .715 12.871 13.713 12.317 12.039 12.722 12.027 13.945 14.162 13.639 15.139 15.487 15.683 17 .214 17 .916 18.483 19.689 17.728 15.083 14.916 14.729 14. 843 14.204 12.839 11.690 11.196 54.403 53.436 52.232 52.265 51.086 50.966 51. 731 50.094 50.044 50. 127 49.185 53 .209 52.957 52.560 52.795 51.459 51. 249 52.100 51. 576 50.962 51. 778 50.214 49.894 49.523 49.818 48.319 48.305 46.999 46.233 46.391 45.468 47.043 46.918 46.119 46.282 44.820 44.544 45.091 44.396 1.00 36.14 1.00 37.95 1.00 37.17 1.00 0.00 1.00 37.05 1.00 38.97 1.00 0.00 1.00 0.00 1.00 36.61 1.00 0.00 1.00 0.00 1.00 36.45 1.00 35.30 1.00 37.25 1.00 0.00 1.00 37.51 1.00 39.21 1.00 42.52 1.00 43.09 1.00 44.41 1.00 44.79 1.00 35.75 1.00 37.66 1.00 33.41 1.00 0.00 1.00 31.60 1.00 37.69 1.00 46.27 1.00 51.86 1.00 54.73 1.00 53.64 1.00 25.93 1.00 24.72 1.00 21.35 1.00 0.00 1.00 19.78 1.00 17.55 1.00 14.77 1.00 9.06 140 ATOM 2644 CEl PTY 315 -7.808 10.163 44.916 1.00 12.12 ATOM 2645 CD2 PTY 315 -9.998 11.117 46.319 1.00 14.36 ATOM 2646 CE2 PTY 315 -9.239 10.085 46.847 1.00 14.01 ATOM 2647 CZ PTY 315 -8.146 9.612 46.145 1.00 14.96 ATOM 2648 OH PTY 315 -7.408 8.580 46.682 1.00 15.26 ATOM 2649 ORi PTY 315 -6.224 9.301 48.730 1.00 15.27 ATOM 2650 0R2 PTY 315 -5.231 9.872 46.71. 1.00 14.33 ATOM 2651 0R3 PTY 315 -5.246 7.621 47.409 1.00 16.50 ATOM 2652 PR PTY 315 -6.018 8.864 47.331 1.00 14.86 ATOM 2653 C PTY 315 -10.349 15.218 43.808 1.00 21.32 ATOM 2654 0 PTY 315 -11.354 15.892 44.034 1.00 22.46 ATOM 2655 N ASP 316 -9.629 15.351 42.707 1.00 22.70 ~.:ATOM 2656 H ASP 316 -8.875 14.753 42.55S 1.00 0.00 ATOM 2657 CA ASP 316 -10.009 16.306 41.684 1.00 24.09 5 ATOM 2658 CB ASP 3 16 -8.770 16.826 40.954 1.00 24.94 *ATOM 2659 CG ASP 316 -7.853 17.622 41.860 1 .00 28.90 :::ATOM 2660 ODi ASP 316 -7.849 18.865 41.756 1.00 32.00 ATOM 2661 0D2 ASP 316 -7.140 17.004 42.681 1. 00 29.88 ATOM 2662 C ASP 316 -10.981 15.691 40.698 1.00 24.49 20 ATOM 2663 o ASP 316 -11.148 14.473 40.646 1.00 23.60 ATOM 2664 N VAL 317 -11.644 16.559 39.948 1.00 27.16 *ATOM 2665 H VAL 317 -11.475 17.521 40.029 1.00 0.00 ATOM 2666 CA VAL 317 -12.605 16.155 38.934 1.00 32.09 ATOM 2667 CB VAL 317 -14.069 16.266 39.437 :.00 35.09 25 ATOM 2-668 CG1 VAL 17 -14. 375 15.156 40.434 1 .0!0 36.22 ATOM 2669 CG2 VAL >7 -14.314 17.636 40.066 1.30 36.89 ATOM 2670 c VAL 317 -12.410 17.095 37.757 1.00 30.78 ATOM 2671 0 VAL 3 17 -11.807 18.159 37.906 1.00 28.67 ATOM -2672 N LEU 318 -12.871 16.684 36.583 1 .00 33.70 ATOM 2673 H LEU 318 -13.315 15.816 36.543 1. 00 0.00 ATOM 2674 CA LEU 3 18 -12.745 17.513 35.395 1.00 36.88 ATOM 2675 CB LEU 318 -13.044 16.699 34.138 1. 00 34.38 ATOM 2 676 CG LEU 318 -12.133 15.505 33 .854 1.00 32.08 ATOM 2677 CD1l LEU 318 -12.560 14.864 32.553 1.00 33.40 ATOM 2678 CD2 LEU 318 -10.678 15.939 33 .775 1. 00 30.49 ATOM 2679 C LELJ 318 -13.698 18.700 35 .492 1.00 41.41 ATOM 2680 0 LEU 318 -14.768 18.604 36.108 1.00 41.34 ATOM 2 681 N ASP 319 -13.282 19.821 34.911 1.00 46.71 ATOM 2682 H ASP 319 -12.447 19.843 34.406 1.00 0.00 141 ATOM 2683 CA ASP 319 -14.072 21.048 34.913 1.00 51.29 ATOM 2684 CB ASP 319 -13.204 22.239 35.340 1.00 53.24 ATOM 2685 CG ASP 319 -11.958 22.400 34.479 1.00 55.43 ATOM 2686 ODi ASP 319 -12.065 22.950 33.361 1.00 58.31 ATOM 2687 0D2 ASP 319 -10.868 21.982 34.923 1.00 58.61 ATOM 2688 C ASP 319 -14.682 21.306 33.535 1.00 52.86 ATOM 2689 0 ASP 319 -14.195 20.701 32.549 1.00 53.27 ATOM 2690 OT ASP 319 -15.634 22.114 33.459 1.00 54.58 ATOM 2691 0H2 H20 501 -16.395 6.573 53.935 1.00 13.04 ATOM 2692 Hl H20 501 -15.625 7.149 54.126 1.00 0.00 ATOM 2693 H2 H20 501 -16.189 6.220 53.062 1.00 0.00 ATOM 2694 0H2 H20 502 -6.900 -1.703 48.537 1.00 15.81 ATOM 2695 Hi H20 502 -6.073 -2.133 48.827 1.00 0.00 ATOM 2696 H2 H20 502 -7.012 -1.023 49.224 1.00 0.00 1 5 ATOM 2697 0H2 H20 503 -7.775 0.446 50.612 1.00 12.12 *ATOM 2698 Hi H20 503 -8.328 0.785 51.329 1.00 0.00 :::ATOM 2699 H2 H20 503 -8.364 0.608 49.869 1.00 0.00 ATOM 2700 0H2 H20 504 -5.965 5.376 45.701 1.00 13 .82 ATOM 2701 Hi H20 504 -5.838 6.191 46.188 1.00 0.00 20 ATOM 2702 H2 H20 504 -5.040 5.192 45.431 1.00 0.00 ATOM 2703 0H2 H20 505 -14.971 -6.776 51.457 1.00 11.75 ATOM 2704 Hi H20 505 -14.401 -7.005 50.693 1.00 0.00 *ATOM 2705 H2 H20 505 -15.747 -6.411 50.986 1.00 0.00 ATOM 2706 0H2 H20 506 -7.399 -1.565 45.723 1.00 20.80 25 ATOM 2707 Hl H2_70 506 -6.869 -0.820 45.388 1.00 0.00 ATOM 2708 H2 H20 506 -7.127 -1.603 46.669 1.00 0.00 ATOM 2709 0H2 H20 507 -3.458 7.189 49.505 1.00 12.46 ATOM 2710 Hi H20 507 -3 .854 6.375 49.171 1.00 0.00 ATOM 2711 H2 H20 507 -4.035 7.857 49.121 1.00 0.00 ATOM 2712 0H2 H20 508 -19.524 4.162 75.938 1.00 31.54 ATOM 2713 Hi H20 508 -20.107 4.703 76.513 1.00 0.00 ATOM 2714 H2 H20 508 -19.510 4.732 75.158 1.00 0.00 ATOM 2715 0H2 H20 509 11.153 11.020 41.619 1.00 23.22 ATOM 2716 Hi H20 509 10.658 10.668 40.869 1.00 0.00 ATOM 2717 H2 H20 509 10.757 11.895 41.712 1.00 0.00 ATOM 2718 0H2 H20 510 -17.729 -5.463 50.658 1.00 8.16 ATOM 2719 Hi H20 510 -18.166 -5.105 49.866 1.00 0.00 ATOM 2720 H2 H20 510 -18.454 -6.018 50.978 1.00 0.00 ATOM 2721 0H2 H20 511 -2.939 4.711 45.111 1.00 12.99 142 got* 0 0 0.0:.

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2722 H1 820 2723 82 H20 2724 082 H20 2725 Hl 820 2726 H2 820 2727 082 820 2728 Hl 820 2729 82 H20 2730 082 H20 2731 Hi 820 2732 82 820 2733 082 820 2734 Hi H20 2735 H2 H20 2736 082 H20 2737 H1 820 2738 82 820 2739 0H2 H20 2740 Hi H20 2741 H2 H20 2742 082 H20 2743 H1 820 2744 H2 820 2745 082 820 2746 Hi 820 2747 82 H20 2748 082 820 2749 81 820 2750 82 820 2751 0H2 820 2752 Hl H20 2753 82 820 2754 082 820 2755 H1 820 2756 82 H20 2757 082 820 2758 H1 820 2759 H2 820 2760 082 820 511 511 512 512 512 513 513 513 514 514 514 515 515 515 516 516 516 517 517 517 518 518 518 519 519 519 520 520 520 521 521 521 522 522 522 523 523 523 524 -2.168 -2.789 -14.697 -15 .286 -13 .856 -4.301 -3 .747 -5 .176 -21. 713 -21.035 -22.251 -10.843 -10.540 -10.110 1.069 1.435 0.143 -4.403 -4.371 -3 .595 -20.848 -20.732 -21.337 -7 .330 -7 .479 -7.935 -12 .664 -12 .180 -13 .550 -11.379 -11.624 -11.994 -15 .662 -15.240 -16.316 4.703 3.917 8.482 8.807 8.877 -4 .082 -3.518 -3.940 7.798 8.271 8.537 5.000 4.529 4.889 6.001 6.888 6.122 -3.111 -3.215 -2.596 12.059 12.086 11. 237 -4.001 -3.098 -4.524 0.989 0.157 0.682 10.139 10.977 9.525 9.282 9 .703 9 .967 45.673 44.596 54.840 55.530 55 .112 45.672 45.097 45.269 61.095 61.588 60. 778 40.733 41.519 40. 111 27.806 27 .776 27.559 48.506 47.537 48.690 58.636 57.675 58.756 44.530 44 .898 45.062 38 .964 39.070 39.238 30.946 30.530 30.519 47.198 46.450 47.478 49.297 48.437 49 .754 42 .957 1.00 0.00 1.00 0.00 1.00 28.53 1.00 0.00 1.00 0.00 1.00 22.83 1.00 0.00 1.00 0.00 1.00 18.35 1.00 0.00 1.00 0.00 1.00 28.99 1.00 0.00 1.00 0.00 1.00 27.31 1.00 0.00 1.00 0.00 1.00 19.12 1.00 0.00 1.00 0.00 1.00 30.17 1.00 0.00 1.00 0.00 1.00 20.45 1.00 0.00 1.00 0.00 1.00 15.59 1.00 0.00 1.00 0.00 1.00 26.07 1.00 0.00 1.00 0.00 1.00 17.30 1.00 0.00 1.00 0.00 1.00 31.49 1.00 0.00 1.00 0.00 1.00 21.38 -11.947 -18.788 -11.710 -18.432 -12.293 -17.992 6.740 2.001 143 ATOM 2761 Hl H20 524 ATM 71 1 2 545.847 2.141 43.289 1.00 0.00 ATOM 2762 H2 H20 524 6.864 1.047 42.981 1.00 0.00 ATOM 2763 0H2 820 525 -8.682 6.518 44.398 1.00 27.19 ATOM 2764 H1 H20 525 -7.791 6.155 44.453 1.00 0.00 ATOM 2765 H2 H20 525 -8.649 7.215 45.061 1.00 0.00 ATOM 2766 082 H20 526 -14.840 3.578 44.839 1.00 22.05 ATOM 2767 H1 H20 526 -15.718 3.347 45.149 1.00 0.00 ATOM 2768 82 H20 526 -14.551 4.227 45.498 1.00 0.00 ATOM 2769 082 H20 527 4.492 23.057 38.874 1.00 25.33 ATOM 2770 H1 820 527 4.800 22.472 38.173 1.00 0.00 ATOM 2771 H2 820 527 5.246 22.944 39.473 1.00 0.00 ATOM 2772 082 820 528 0.375 -17.917 41.574 1.00 56.36 *ATOM 2773 H1 820 528 -0.351 -18.113 42.169 1.00 0.00 se*ATOM 2774 H2 820 528 -0.043 -17.548 40.796 1.00 0.00 15 ATOM 2775 082 H20 529 7.016 14.850 51.046 1.00 20.70 ATOM 2776 H1 820 529 6.142 14.448 50.870 1.00 0.00 TM 77 2 82 2 6.980 15.645 50.511 1.00 0.00 ATOM 2778 082 820 530 -7.683 -1.801 42.232 1.00 34.83 ::ATOM 2779 H1 820 530 -8.052 -1.273 42.957 1.00 0.00 20 ATOM 2780 82 820 530 -7.249 -2.522 42.702 1.00 0.00 ATOM 2781 082 820 531 -21.235 6.653 69.461 1.00 40.97 ***ATOM 2782 81 820 531 -22.089 6.966 69.119 1.00 0.00 *ATOM 2783 82 820 531 -21.371 6.744 70.411 1.00 0.00 ATOM 2784 082 820 532 0.051 -0.240 27.111 1.00 38.10 25 ATOM 2785 H1 H20 532 -0.526 -0.554 26.406 1.00 0.00 ATOM 2786 H2 820 532 0.153 0.695 26.895 1.00 0.00 ATOM 2787 082 820 533 4.720 13.526 50.274 1.00 24.25 ATOM 2788 81I H20 533 3.779 13.360 50.353 1.00 0.00 ATOM 21789 82 820 533 5.030 12.691 49.901 1.00 0.00 ATOM 2790 082 820 535 -24.439 -4.493 65.220 1.00 19.89 ATOM 2791 81 8 20 535 -23.921 -4.800 64.468 1.00 0.00 ATOM 2792 82 820 535 -23.970 -4.918 65.943 1.00 0.00 ATOM 2793 082 820 536 -24.821 -8.124 64.414 1.00 26.52 ATOM 2794 H1 820 536 -25.733 -8.277 64.141 1.00 0.00 ATOM 2795 82 820 536 -24.637 -7.232 64.092 1.00 0.00 ATOM 2796 082 820 537 -1.448 9.507 51.754 1.00 14.14 ATOM 2797 81 820 537 -2.234 9.866 52.178 1.00 0.00 ATOM 2798 82 820 537 -1.227 8.752 52.319 1.00 0.00 ATOM 2799 082 820 538 -19.810 -23.909 45.616 1.00 42.72 144 ATOM 2800 ATOM 2801 ATOM 2802 ATOM 2803 ATOM 2804 ATOM 2805 ATOM 2806 ATOM 2807 ATOM 2808 ATOM 2809 ATOM 2810 ATOM 2811 ATOM 2812 ATOM 2813 1 5 ATOM 2814 ATOM 2815 ATOM 2816 ATOM 2817 ATOM 2818 20 ATOM 2819 ATOM 2820 ATOM 2821 ATOM 2822 ATOM 2823 25 ATOM 2824 ATOM 2825 ATOM 2826 ATOM 2827 ATOM 2828 ATOM 2829 ATOM 2830 ATOM 2831 ATOM 2832 ATOM 2833 ATOM 2834 ATOM 2835 ATOM 2836 ATOM 2837 Hl H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 HI H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hl H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hl H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 HI H20 H2 H20 0H2 H20 HI H20 H2 H20 538 538 539 539 539 540 540 540 541 541 541 542 542 542 543 543 543 544 544 544 545 545 545 546 546 546 547 547 547 549 549 549 550 550 550 5 51 551 551 -20.226 -24.776 -19.298 -24.029 -6.034 -10.821 -6.800 -10.777 -5.304 -10.964 -20.033 10.958 -19.256 10.718 -20.491 10.121 -5.125 -7.851 -4.372 -8.168 -5.411 -7.104 -1.080 20.333 -1.337 19.477 -1.916 20.809 5.975 26.290 6.265 26.840 6.741 26.247 -13.632 -13.848 -13.441 -13.263 -13.685 -13.228 45.518 46.420 42.457 43 .033 43 .068 50.001 50.512 49.920 62.359 61 .862 61.798 46.689 47.057 46.638 37.583 36.852 38.153 50.081 50.817 49.342 46.579 47.182 46.353 73 .627 73 .390 72.791 22 .576 23 .054 21.766 51 .470 51.186 50.637 74.340 73 .541 74.046 65 .322 66.091 65 .504 1.00 0.00 1.00 0.00 1.00 29.94 1.00 0.00 1.00 0.00 1.00 31.83 1.00 0.00 1.00 0.00 1.00 38.63 1.00 0.00 1.00 0.00 1.00 26.15 00 0.00 1.00 0.00 1.00 43.59 1.00 0.00 1.00 0.00 1.00 27.21 1.00 0.00 1.00 0.00 1.00 32.58 1.00 0.00 1.00 0.00 1.00 51.06 1.00 0.00 1.00 0.00 1.00 43.45 1. 00 0.00 1.00 0.00 1.00 32.88 1.00 0.00 1.00 0.00 1.00 33.79 1.00 0.00 1.00 0.00 1.00 28.70 1.00 0.00 1.00 0.00 6 .897 7.538 7 .296 -19.007 -18 .833 -18.795 -0 .107 -0.622 0.140 -20.845 -20.910 -20.734 -18.995 -19.031 -18.620 -29.193 -29.521 -28.243 4.096 4.515 3.250 6.577 7.495 6 .148 9.991 10. 655 10.441 -8.815 -9.731 -8.346 -8.847 -9.373 -8.012 1.529 1.026 1.541 ATOM 2838 0H2 H20 552 -9.376 -14.036 60.634 1.00 39.70 145 ATOM 2839 Hl H2O 552 -9.678 -14.141 5.2 .0 00 59.724 1.00 0.00 ATOM 2840 ATOM 2841 ATOM 2842 ATOM 2843 ATOM 2844 ATOM 2845 ATOM 2846 ATOM 2847 1 0 ATOM 2848 ATOM 2849 ATOM 2850 ATOM 2851 ATOM 2852 1 5 ATOM 2853 ATOM 2854 ATOM 2855 ATOM 2856 ATOM 2857 20 ATOM 2858 ATOM 2859 ATOM 2860 ATOM 2861 ATOM 2862 ATOM 2863 ATOM 2864 ATOM 2865 ATOM 2866 ATOM 2867 ATOM 2868 ATOM 2869 ATOM 2870 ATOM 2871 ATOM 2872 ATOM 2873 ATOM 2874 ATOM 2875 ATOM 2876 ATOM 2877 H2 H20 0H2 H20 Hl H20 H2 H20 0H2 H20 HI H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 552 553 553 553 554 554 554 555 555 555 556 556 556 557 557 557 558 558 558 559 559 559 560 560 560 561 561 561 563 563 563 569 569 569 570 570 570 572 -8.558 15.303 15.256 14.945 -6.351 -5.433 -6.453 -26.688 -27.261 -26.730 -27.507 -26.716 -27.089 -3.466 -4.116 -3.730 -17.363 -18.067 -17.568 -5.182 -6.102 -4.870 -1.672 -1.378 -1.186 -12.968 -13.869 -12.756 8.438 7 .987 9 .187 -18.518 -19 .475 -18.362 -3.123 -2 .857 -2.642 -4.725 -14.547 7.535 8.508 7.223 -6.041 -5.940 -6.976 -2.898 -2.128 -3.318 -2.530 -3.098 -1.666 0.091 0. 662 0 .129 11.081 11.741 10.638 1.100 0.891 0.273 -2 .171 -1.786 -1.638 -16.434 -16.305 -15.504 5 .804 5.826 6.397 8.907 8.882 9.599 15.254 15.725 14.427 17.961 60.629 43.610 43.528 42.779 58.195 58.470 58.404 68.239 68.123 67.372 64.808 64.836 64.684 55.103 54 .672 56 .022 48 .313 48.280 49.148 51. 170 50 .910 51.539 49 .168 48.327 49 .811 50.268 49.955 50.450 48.097 48.951 48.249 70.572 70.611 69 .917 51. 267 50 .474 51.213 46.351 1.00 0.00 1.00 43.10 1.00 0.00 1.00 0.00 1.00 39.35 1.00 0.00 1.00 0.00 1.00 26.60 1.00 0.00 1.00 0.00 1.00 35.40 1.00 0.00 1.00 0.00 1.00 31.58 1.00 0.00 1.00 0.00 1.00 34 .37 1.00 0.00 1.00 0.00 1.00 35.10 1.00 0.00 1.00 0.00 1.00 30.93 1.00 0.00 1.00 0.00 1.00 38.85 1.00 0.00 1.00 0.00 1.00 48.55 1.00 0.00 1.00 0.00 1.00 33.67 1.00 0.00 1.00 0.00 1.00 44.68 1.00 0.00 1.00 0.00 1.00 28.78 146 0.

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2878 2879 2880 2881 2882 2883 2884 2885 2886 2887 2888 2889 2890 2891 2892 2893 2894 2895 2896 2897 2898 2899 2900 2901 2902 2903 2904 2905 2906 2907 2908 2909 2910 2911 2912 2913 2914 2915 Hl H20 H2 H20 082 H20 Hi 820 H2 H20 082 H20 Hi 820 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi 820 H2 H20 0H2 820 Hi H20 H2 820 0H2 H20 Hi H20 H2 H20 082 H20 Hi 820 82 820 082 820 Hi~ H20 H _7 H20 082 820 Hi I820 H2 820 082 H20 Hi 8 20 H2 820 082 820 H! 820 H2 820 082 820 H1 820 H2 H20 572 572 573 573 573 574 574 574 575 575 575 576 576 576 577 577 577 5-79 579 579 580 580 580 581 581 ;58 1 582 582 582 583 583 583 584 584 584 585 585 585 -7.797 -8 .151 042 -2 .183 -3 .094 -1.964 -0.855 -1.157 -0.947 3.333 3 .451 4 .217 -2 .444 -3.317 -2.660 -15.655 -14.694 .5 .902 2 .063 1.349 2 .119 -6.779 -6.999 -7.664 11.799 12.475 11.657 -13.524 -12.588 -13.692 6.237 5.827 6.728 3 .330 3.131 4.076 -5.759 -5.188 -6 .645 6.242 5.332 6. 487 2.334 2.148 3.049 7 .091 7. 06 6 6.185 24.320 24.295 25.295 -2.271 -1.707 -2.443 8.386 8 .197 9.325 6.050 5.799 5.671 -5.641 18.255 -4.454 18.331 -17.831 -26.994 -18.168 -27.861 -16.954 -27.236 -11.347 -10.955 -12.285 -11.031 -11.302 -10.452 46.416 45.500 47.079 47.345 46.737 43.461 43.636 42.652 24.140 23.336 23.794 69.045 68.802 68.483 42.695 41.984 42.342 53.401 53.701 53.105 61.039 61.413 60 .423 35.775 35.713 35.548 47.146 46 .468 47.172 28.633 27.886 28.970 47.735 47 .055 47 .602 40.840 40.707 41.705 1.00 0.00 1.00 0.00 1.00 47.81 1.00 0.00 1.00 0.00 1.00 27.59 1.00 0.00 1.00 0.00 1.00 43.37 1.00 0.00 1.00 0.00 1.00 33.93 1.00 0.00 1.00 0.00 1.00 25.76 1.00 0.00 1.00 0.00 1.00 50.25 1.00 0.00 1.00 0.00 1.00 31.46 1.00 0.00 1.00 0.00 1.00 37.09 1.00 0.0 1.00 0.00 1.00 51.91 1.00 0.00 1.00 0.00 1.00 40.33 1.00 0.00 1.00 0.00 1.00 53.26 1.00 0.00 1.00 0.00 1.00 43.92 1.00 0.00 1.00 0.00 ATOM 2916 082 H20 586 -20.205 -18.799 46.340 1.00 35.53 147 ATOM 2917 ATOM 2918 ATOM 2919 ATOM 2920 ATOM 2921 ATOM 2922 ATOM 2923 ATOM 2924 ATOM 2925 1 0 ATOM 2926 ATOM 2927 ATOM 2928 ATOM 2929 ATOM 2930 1 5 ATOM 2931 ATOM 2932 ATOM 2933 ATOM 2934 ATOM 2935 ATOM 2936 ATOM 2937 ATOM 2938 ATOM 2939 ATOM 2940 ATOM 2941 ATOM 2942 ATOM 2943 ATOM 2944 ATOM 2945 ATOM 2946 ATOM 2947 ATOM 2948 ATOM 2949 ATOM 2950 ATOM 2951 ATOM 2952 ATOM 2953 ATOM 2954 ATOM 2955 H1 H20 H2 H20 0H2 820 H1 H20 H2 H20 082 H20 H1 H20 82 H20 0H2 820 Hi H20 82 H20 082 H20 H1 820 82 H20 0H2 820 Hi 820 82 H20 0H2 820 H1 820 82 H20 082 820 Hi 820 82 820 082 820 Hl 820 82 820 082 820 Hi 820 82 820 082 H20 H1 820 82 820 082 820 Hi 820 82 820 082 820 Hi 820 82 820 082 820 586 586 587 587 587 588 588 588 589 589 589 592 592 592 593 593 593 594 594 594 595 595 595 596 596 596 597 597 597 598 598 598 599 599 599 601 601 601 602 9.685 8.918 10.422 -18.278 -17.821 -18.442 12.004 11.783 12.929 -25.871 -26.445 -25.440 -13 .120 -12.211 -13 .553 -2 .642 -2 .754 -3.443 13 .645 14.505 13 .921 11.562 11.768 12.242 8.860 8 .422 8 .194 14.739 14.760 15 .049 -14.758 -15.399 -14.534 11.055 10.283 11.463 -7.939 9.586 9.519 9 .526 15 .597 15.619 14.652 9 .442 9.993 9.683 -5.699 -5.733 847 10.109 9.803 9 .578 17.050 17.725 17.194 7.886 7.762 7.739 6.029 5.826 6.714 -0.601 -0.896 -0.773 10.248 11. 112 10.456 -0.522 -0.544 -1.454 1.025 0.434 0.920 5 .076 -20.221 -18.803 -19.889 -17.914 47.304 46.132 28.857 28.276 28.241 52 .143 52.985 52.046 43.787 43 .008 43 .951 57.447 58.226 57.572 38.496 38.544 39.173 48 .010 48.682 47.462 45 .763 46 .191 44.837 45 .973 46.893 45. 805 32 .747 31.940 33.420 44. 027 43 .590 44.920 39.901 39.178 39 .996 33.198 33.099 32.328 74.158 1.00 0.00 1.00 0.00 1.00 23.20 1.00 0.00 1.00 0.00 1.00 37.65 1.00 0.00 1.00 0.00 1.00 36.10 1.00 0.00 1.00 0.00 1.00 24.88 1.00 0.00 1.00 0.00 1.00 33 .36 1.00 0.00 1.00 0.00 1.00 31.60 1.00 0.00 1.00 0.00 1.00 41.58 1.00 0.00 1.00 0.00 1.00 50.87 1.00 0.00 1.00 0.00 1.00 41.20 1.00 0.00 1.00 0.00 1.00 61.01 1.00 0.00 1.00 0.00 1.00 47.63 1.00 0.00 1.00 0.00 1.00 33.67 1.00 0.00 1.00 0.00 1.00 35.51 148 ATOM 2956 Hl H20 602 ATM 96 1 2 62 -7.267 5.133 74.849 1.00 0.00 ATOM 2957 ATOM 2958 ATOM 2959 ATOM 2960 ATOM 2961 ATOM 2962 ATOM 2963 ATOM 2964 1 0 ATOM 2965 ATOM 2966 ATOM 2967 ATOM 2968 ATOM 2969 1 5 ATOM 2970 ATOM 2971 ATOM 2972 ATOM 2973 ATOM 2974 20 ATOM 2975 ATOM 2976 ATOM 2977 ATOM 2978 ATOM 2979 ATOM 2980 ATOM 2981 ATOM 2982 ATOM 2983 ATOM 2984 ATOM 2985 ATOM 2986 ATOM 2987 ATOM 2988 ATOM 2989 ATOM 2990 ATOM 2991 ATOM 2992 ATOM 2993 ATOM 2994 82 820 0H2 H20 H1 H20 H2 H20 082 H20 H1 H20 H2 H20 0H2 H20 81 820 H2 820 082 H20 HI 820 82 H20 082 820 H1 820 82 820 082 820 Hl 820 82 820 082 H20 81 H20 82 H20 0H2 820 H1 820 H2 H20 082 820 H1 820 82 H20 082 820 H1 820 82 820 082 820 81 820 82 820 082 820 Hl 820 82 820 082 820 602 603 603 603 604 604 604 605 605 605 606 606 606 608 608 608 609 609 609 610 610 610 611 611.

611 612 612 612 613 613 613 614 614 614 615 615 615 616 -7.784 4.156 -16.636 -12.874 -16.225 -13.402 -15.849 -12.404 -18.358 -20.653 -17.998 -20.559 -17.638 -20.311 -5.855 -5.527 -6.476 -5.558 -5.861 -4.592 -7.119 -2.334 -7.787 -1.638 -7.562 -3.033 -4.292 10.348 -3.677 9.723 -3.683 10.944 -4.131 23.593 -4.310 24.395 -4.950 23.104 -13.858 -29.598 -13.564 -29.123 -14.093 -30.430 73 .888 62.037 61.337 62 .373 39.617 40.507 39.059 60.942 60 .199 61 .176 35.830 35.776 35.342 58.969 59 .379 58.518 29.611 30.105 29.684 37.538 38.335 37 .979 55.419 56.337 54.942 72 .803 73 .608 72.631 37.069 36.781 37.165 65.955 65 .941 65.146 31.945 31.506 32.733 38.360 1.00 0.00 1.00 36.29 1.00 0.00 1.00 0.00 1.00 36.43 1.00 0.00 1.00 0.00 1.00 35.83 1.00 0.00 1.00 0.00 1.00 31.03 1.00 0.00 1.00 0.00 1.00 59.16 1.00 0.00 1.00 0.00 1.00 48.52 1.00 0.00 1.00 0.00 1.00 34.23 1.00 0.00 1.00 0.00 1.00 26.60 1.00 0.00 1.O 0.00 100 53.47 1.00 0.00 1.00 0.00 1.00 50.82 1.00 0.00 1.00 0.00 1.00 46.58 1.00 0.00 1.00 0.00 1.00 33.74 1.00 0.00 1.00 0.00 1.00 46.62 -20.921 -21.180 -21.260 -26 .331 -26.140 -27.255 -13 .525 -14.442 -13 .355 -21.926 -22 .637 -22.048 1.690 1.397 2 .121 -20.949 -9.179 -9.388 -9.951 -2.023 -1.532 -1.793 13.983 14. 000 13 .043 16.371 17.013 15.876 -5.302 -6.113 -5.661 -21.416 149 ATOM 2995 H1 H20 616 -20.201 -21.991 38.548 1.00 0.00 ATOM 2996 H2 H20 616 -20.536 -20.560 38.533 1.00 0.00 ATOM 2997 0H2 H20 617 -12.061 10.750 73.270 1.00 33.05 ATOM 2998 Hi H20 617 -12.819 11.023 72.742 1.00 0.00 ATOM 2999 82 H20 617 -11.922 9.855 72.958 1.00 0.00 ATOM 3000 0H2 H20 618 -15.349 12.400 63.729 1.00 37.51 ATOM 3001 Hi H20 618 -15.377 11.908 62.908 1.00 0.00 ATOM 3002 H2 H20 618 -16.272 12.641 63.835 1.00 0.00 ATOM 3003 0H2 820 619 0.949 7.386 53.643 1.00 49.12 1 0 ATOM 3004 Hi H20 619 1.002 7.867 54.473 1.00 0.00 ATOM 3005 H2 H20 619 1.831 6.951 53.624 1.00 0.00 ATOM 3006 082 820 620 -4.534 -8.391 59.287 1.00 32.23 ATOM 3007 Hl 820 620 -4.887 -9.282 59.417 1.00 0.00 ***ATOM 3008 H2 820 620 -3.858 -8.571 58.625 1.00 0.00 1 15 ATOM 3009 082 820 621 -25.465 -6.264 54.21. 1.00 48.91 ***ATOM 3010 Hi H20 621 -24.522 -6.048 54.259 1.00 0.00 :***ATOM 3011 H2 820 621 -25.496 -6.709 53.362 1.00 0.00 ATOM 3012 082 820 622 -28.810 -0.917 66.953 1.00 54.26 *ATOM 3013 H1 820 622 -28.968 -1.765 66.514 1.00 0.00 20 ATOM 3014 82 820 622 -28.017 -0.623 66.496 1.00 0.00 ATOM 3015 082 820 623 -1.838 20.090 25.125 1.00 53.05 *ATOM 3016 Hl 820 623 -1.624 20.918 24.699 1.00 0.00 ATOM 3017 H2 820 623 -2.056 19.496 24.392 1.00 0.00 ATOM 3018 082 820 624 4.169 12.348 27.338 1.00 59.51 25 ATOM 3019 Hl 820 624 3 .885 11.758 26.634 1.00 0.00 ATOM 3020 82 820 624 3.382 12.887 27.475 1.00 0.00 ATOM 3021 082 820 625 -20.172 -12.484 57.970 1.00 48.36 ATOM 3022 H1 820 625 -20.919 -12.902 58.402 1.00 0.00 ATOM 3023 82 820 625 -19.544 -12.424 58.696 1.00 0.00 ATOM 3024 082 820 626 -2.341 -0.010 29.093 1.00 41.65 ATOM 3025 H1 820 626 -2.634 -0.652 29.755 1.00 0.00 ATOM 3026 82 820 626 -1.592 -0.477 28.705 1.00 0.00 ATOM 3027 082 820 627 -5.808 -1.656 39.529 1.00 30.08 ATOM 3028 Hi 820 627 -6.395 -1.472 38.788 1.00 0.00 ATOM 3029 82 820 627 -5.340 -0.821 39.617 1.00 0.00

END

'Note: See copyright notice on page 1.

150 Appendix 11: Coordinates for the 3D structure of ZAP-NC:z2* REMARK FILENAME= "tml- zeta2 -watl- slow. pdb" REMARK TOPH19.pep -MACRO for protein sequence created by user: marcos

ATOM

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1 5 ATOM

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25 AT,-OM

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ATO_ 0M

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ATOM

CB ASP CG ASP ODI ASP 0D2 ASP C ASP 0 ASP HT1 ASP HT2 ASP N ASP HT3 ASP CA ASP N PRO CD PRO CA PRO CB PRO CG PRO C PRO O PRO N ALA H ALA CA ALA CS ALA C ALA O ALA N ALA H ALA CA ALA CE ALA C ALA O ALA N HIS H HIS CA HIS -1.930 -2.570 -2.370 -3.265 -2.096 -0.916 -1.022 -2.470 -2 .058 -2.314 -2.531 -3.057 -4.493 -2.860 -4.273 -5.115 -1.929 -1.563 -1.585 -1.962 -0.713 -1.363 0. 662 1.560 0.849 0.133 2 .118 2.037 3 .373 4.455 3.238 2.333 4.393 -4.782 -3 .408 -2.527 -3 .205 -4.960 -4.974 -6 .965 -7.515 -6.982 -7.428 -5.568 -4.449 -4.558 -3.823 -3.399 -4.444 -2.616 -2.119 -2.121 .491 -0.963 0.104 -1.303 -0.474 -2.545 -3.204 -2.982 -4.448 -2.730 -2.560 -2.712 -2.845 -2-.487 36.991 37 .176 36.311 38.197 34.485 34.145 35.742 35.059 35 .850 36.750 35.816 33.704 34.013 32.394 32.011 32.653 32.393 31.324 33 .578 34.379 33 .682 34.546 34.222 34.167 34.663 34.566 35.250 35.644 34.420 34.970 33 .100 32.758 32 .234 1.00 37.05 1.00 38.16 1.00 37.36 1.00 37.01 1.00 32.75 1.00 31.91 1.00 0.00 1.00 0.00 1.00 39.84 1.00 0.00 1.00 35.10 1.00 29.48 1.00 31.76 1.00 27.70 1.00 30.04 1.00 32.47 1.00 26.07 1.00 27.89 .00 20.52 1.00 0.00 2.00 15.66 1.00 12.37 1.00 15.18 1.00 15.42 1.00 17.31 1.00 0.00 1.00 15.36 1.00 16.18 1.00 14.64 1.00 15.69 1.00 13 .68 1.00 0.00 1.00 11.91 151

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1 5 ATOM

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34 CB HIS 35 CG HIS 36 CD2 HIS 37 ND1 HIS 38 HD1 HIS 39 CEl HIS 40 NE2 HIS 41 HE2 HIS 42 C HIS 43 0 HIS 14 N LEU 15 H LEU 16 CA LEU 17 CB LEU 18 CG LEIJ 19 CD1 LEU io CD2 LEU C LEU 2 0 LEU 3 N PRO 4 CD PRO ,5 CA PRO 6 CB PRO 2.990 2.861 1.712 1.443 0.848 1.524 1.115 4.726 5.780 3.821 3.016 4.035 2.733 1.807 2.031 0.373 5.129 5.059 6.142 6.257 7.279 8.087 7.724 6 .867 7.567 5.752 5.256 5.247 4 .772 3.822 2.445 4.308 1.563 3.439 2.060 4.141 3 .387 4.020 -2.727 -1.908 -3 .118 -3.762 -2.558 -1.820 -1.305 -1.012 -0.688 -0.121 -0.410 1 .317 2.076 2.318 1.303 2.309 1.799 1.576 2.500 2 .872 3.032 3.778 3 .094 3 .997 4.134 4.688 4.547 5 .667 6 .929 6 .646 6 .666 6 .349 6.390 6 .074 6 .095 5 .125 5.898 3.802 30.134 1.00 6.98 29.064 1.00 8.55 30.470 1.00 6.26 31.161 1.00 0.00 29.642 1.00 9.39 28.778 1.00 9.77 28.037 1.00 0.00 32.019 1.00 11.78 31.479 1.00 15.61 32.421 1.00 11.63 32.904 1.00 0.00 32.271 1.00 11.65 32.536 1.00 12.00 31.340 1.00 14.44 30.248 1.00 14.24 31.804 1.00 13.16 33.213 1.00 10.74 34.419 1.00 13.97 32.676 1.00 11.59 31.256 1.00 10.31 33.439 1.00 9.53 32.373 1.00 10.55 31.115 1.00 10.88 34.548 1.00 8.58 35.550 1.00 10.26 34.340 1.00 7.17 33.516 1.00 0.00 35.295 1.00 8.06 34.553 1.00 4-S6 4.199 -3.186 30.884 1.00 11.56 a

PRO

PRO

PRO

PHE

PHE

PHE

PHE

CG PHE CD1 PE CD2 PE CEl PE CE2 PHE CZ PE C PE 0 PE N PHE 33.425 33.629 32.152 32.578 31. 103 31. 315 36.203 36.795 36.280 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 6.98 7.37 6.47 8.56 8.81 8.30 9 .03 9.71 7.91 152

ATOM

73 H PHE 11 4.649 3.204 35.823 1.00 0.00

ATOM

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ATOM

S

S

ATOM 78 ATOM 79 ATOM 80 ATOM 81 ATOM 82 ATOM 83 ATOM 84 ATOM 85 ATOM 86 ATOM 87 ATOM 88 ATOM 89 ATOM 90 ATOM 91 ATOM 92 ATOM 93 ATOM 94 ATOM 95 ATOM 96 ATOM 97 ATOM 98 ATOM 99 ATOM 100 ATOM 101 ATOM 102 ATOM 103 ATOM 104 ATOM 105 ATOM 106 ATOM 107 ATOM 108 ATOM 109 ATOM 110 ATOM 111 CA PHE CB PHE CG PHE CD1 PHE CD2 PHE CE1 PHE CE2 PHE CZ PHE C PHE O PHE N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CE1 TYR CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR C TYR O TYR N GLY H GLY CA GLY C GLY O GLY N SER H SER CA SER CB SER OG SER HG SER C SER O SER N ILE 3.026 2.404 1.383 0.206 1.603 -0.729 0.668 -0.497 3.725 4.710 3.231 2.469 3.836 3.996 5.066 4.862 5.858 6.294 7.289 7.063 8.068 8.910 3.114 3.554 2.000 1.656 1.262 0.420 -0.098 0.315 0.788 -0.496 -1.162 -2.009 -1.439 0.210 0.467 0.522 3.166 1.964 1.237 1.864 -0.078 1.192 -0.761 -0.130 2.725 1.983 3.202 3.818 2.870 4.130 5.063 5.836 6.672 5.156 5.987 6.740 7.546 7.326 1.805 1.428 1.325 1.690 0.299 0.849 1.960 0.087 -0.773 0.492 -0.737 -0.370 -0.023 1.316 0.820 2.570 37.137 36.427 37.251 37.635 37.642 38.389 38.401 38.775 38.434 38.400 39.573 39.520 40.860 41.706 41.193 40.051 39.569 41.840 41.367 40.234 39.779 40.171 41.662 42.749 41.139 40.302 41.842 42.974 42.888 44.056 44.102 45.190 45.810 46.884 47.586 46.265 47.363 45.950 1.00 7.22 1.00 7.31 1.00 5.77 1.00 2.00 1.00 2.95 1.00 3.12 1.00 2.87 1.00 2.00 1.00 7.69 1.00 5.93 1.00 6.36 1.00 0.00 1.00 5.86 1.00 7.27 1.00 8.07 1.00 7.30 1.00 7.12 1.00 7.58 1.00 7.70 1.00 8.65 1.00 12.68 1.00 0.00 1.00 5.87 1.00 5.79 1.00 5.99 1.00 0.00 1.00 11.58 1.00 13.90 1.00 13.74 1.00 14.19 1.00 0.00 1.00 15.17 1.00 14.68 1.00 23.05 1.00 0.00 1.00 16.00 1.00 16.80 1.00 15.37 153 ATOM 112 H ILE 15 ATM 12 H L 50.283 2.901 45.058 1.00 0.00

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15 ATOM

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ATOM

ATOM

113 114 115 116 117 118 119 120 121 122 123 124 125 CA ILE CB ILE CG2 ILE CG1 ILE CD ILE C ILE 0 ILE N SER H SER CA SER CB SER OG SER HG SER 126 C SER 127 0 SER 128 N ARC 129 H ARG 130 CA ARC 131 CB ARC 132 CG ARG 133 CD ARG 134 NE ARG 135 HE ARG 136 CZ ARG 137 NH1 ARG 138 HH11 ARG 139 HH12 ARG 140 NH2 ARG 141 HH21 ARG 142 HH22 ARG 143 c ARC 144 0 ARC 145 N ALA 146 H ALA 147 CA ALA 148 CB ALA 149 c ALA 150 o ALA 1.159 2.370 3 .496 1.945 3 .062 0.120 -0.990 0.469 1.358 -0.459 -0.231 1.051 1.119 -0.267 0.727 -1.209 -1.975 -1 .137 -2.328 -2.230 -3.359 -4.651 -4.764 -5.667 -5.547 -4.683 -6.311 -6 .807 -6 .903 -7 .576 0.142 0.814 0.470 -0.131 1.674 1.787 2.904 3.764 4.223 3.237 5 .032 5 .887 4.473 4.555 5.233 5.201 6.215 6.398 6.950 7.092 7.549 7.753 8.461 8.225 9.792 10.640 12 .078 12.936 12.497 11.542 13.308 14.615 14.986 15.229 12.807 11. 820 13.416 10.462 11. 133 10.286 9.780 10.877 10.544 10.405 11.209 46.304 45.986 45.074 44.496 47.426 46.889 48.459 48.836 49.010 50.512 50.758 51.719 48.316 47.608 48.549 49.117 47.969 48.407 47.919 48.428 47.919 47.799 47 .651 47.839 48.174 47 .642 47 .199 47 .061 47 .005 48.432 47 .657 49.704 50.291 50.267 51 .747 49.526 49.168 3-467 46-914 1.00 12.48 1.00 10.89 1.00 8.22 1.00 7.10 1.00 2.93 1.00 12.27 1.00 11.25 1.00 8.90 1.00 0.00 1.00 10.27 1.00 7.24 1.00 11.57 1.00 0.00 1.00 8.08 1.00 5.74 1.00 8.03 1.00 0.00 1.00 7.35 1.00 6.44 1.00 5.73 1.00 7.10 1.00 10.08 1.00 0.00 1.00 12.64 1.00 14.72 1.00 0.00 1.00 0.00 1.00 14.47 1.00 0.00 1.00 0.00 1.00 7.25 1.00 11.16 1.00 8.87 1.00 0.00 1.00 7.33 1.00 12.14 1.00 7.31 1.00 8.68 154 ATOM 151 ATOM 152 ATOM 153 ATOM 154 ATOM 155 ATOM 156 ATOM 157 ATOM 158 ATOM 159 ATOM 160 ATOM 161 ATOM 162 ATOM 163 ATOM 164 1 5 ATOM 165 ATOM 166 ATOM 167 ATOM 168 ATOM 169 ATOM 170 ATOM 171 ATOM 172 ATOM 173 ATOM 174 ATOM 175 ATOM 176 ATOM 177 ATOM 178 ATOM 179 ATOM 180 ATOM 181 ATOM 182 ATOM 183 ATOM 184 ATOM 185 ATOM 186 ATOM 187 ATOM 188 ATOM 189 N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU OE2 GLU C GLU O GLU N ALA H ALA CA ALA CB ALA C ALA O ALA N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU OE2 GLU C GLU O GLU N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU OE2 GLU C GLU O GLU N HIS H HIS CA HIS 2.987 2.260 4.127 4.061 4.085 3.901 4.912 2.748 4.166 5.239 2.987 2.170 2.882 1.432 3.421 4.178 3.042 2.458 3.474 2.621 1.166 0.276 -0.882 0.716 4.960 5.595 5.521 4.964 6.941 7.291 8.772 9.231 8.381 10.461 7.754 8.739 7.330 6.513 8.009 9.100 8.510 8.530 7.005 6.415 4.909 4.190 4.439 9.050 9.289 9.229 9.017 9.738 9.702 11.165 11.510 11.981 11.637 13.371 14.156 14.213 15.052 15.278 15.489 13.520 14.470 12.563 11.853 12.584 11.489 11.140 10.377 9.865 10.304 12.407 13.111 11.473 10.983 11.199 49.292 49.603 48.580 48.589 49.986 50.005 50.112 49.931 47.150 46.596 46.560 47.052 45.197 44.731 45.122 44.216 46.097 46.807 46.142 47.132 46.698 47.594 47.213 48.674 46.434 45.982 47.159 47.531 47.458 48.465 48.465 49.691 50.457 49.887 46.173 45.949 45.326 45.570 44.060 1.00 8.47 1.00 0.00 1.00 7.37 1.00 9.12 1.00 18.39 1.00 18.70 1.00 27.52 1.00 16.92 1.00 8.14 1.00 8.18 1.00 8.26 1.00 0.00 1.00 9.21 1.00 7.13 1.00 7.93 1.00 7.73 1.00 8.72 1.00 0.00 1.00 8.14 1.00 3.54 1.00 4.77 1.00 3.41 1.00 3.53 1.00 8.91 1.00 7.55 1.00 10.13 1.00 6.89 1.00 0.00 1.00 7.66 1.00 9.80 1.00 20.65 1.00 26.23 1.00 27.98 1.00 27.22 1.00 8.48 1.00 11.39 1.00 10.23 1.00 0.00 1.00 7.78 155 ATOM 190 CB HIS 23 ATO 19 CEHIS 23 7.420 9.954 43.388 1.00 6.65 9 9.99 9 9.

9 *9*9 9 *9*9 .9 9

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

191 CG HIS 192 CD2 HIS 193 ND1l HIS 194 HD1l HIS 195 CEl HIS 196 NE2 HIS 197 HE2 HIS 198 C HIS 199 0 HIS 200 N LEU 201 H LEU 202 CA LEU 203 CE LEU 204 CG LEU 205 CD1 LEU 206 CD2 LEU 207 C LEU 208 0 LEU 209 N LYS 210 H LYS 211 CA LYS 212 CE LYS 213 CG LYS 2-14 C:D LYS -15 CE LYS 216 NZ LYS 217 HZ1 LYS 218 HZ2 LYS 219 HZ3 LYS 220 C LYS 221 0 LYS 222 N LEU 223 H LEU 224 CA LEU 225 CB LEU 226 CC LEU 227 CD1 LEU 228 CD2 LETJ 7.813 9.015 6.902 5.953 7.522 8.808 9.497 7.923 8.893 6 .758 6.007 6.551 5 .062 4 .140 2 .672 4.441 7 .401 7 .973 7 .521 7 .026 8.343 8 .178 6 .849 6.863 5.533 5 .612 6.355 5.830 4. 697 9 .815 10.518 10.274 9.655 11.664 11.967 12.030 12.144 13 .196 8.667 8.056 7. 835 8.008 6.767 6.879 6.257 12.380 12.698 13.016 12.724 14. 164 14.527 13.522 13.866 13 .479 15.340 16 .072 15.497 14.908 16.562 16. 621 17.130 17.140 17.549 17.513 18.162 16.546 17.805 16.312 17.204 15..086 14.414 14.721 13.322 13 .127 11. 659 13.880 44.047 44.166 44.661 44.836 45.125 44. 838 45.178 43.102 42.412 43.049 43 .606 42.174 42.112 41.392 41.630 39.889 42.654 41.843 43 .969 44.577 44.540 46.058 46.550 48.059 48.656 50.147 50.481 50.457 50.540 44.214 43 .741 44.450 44.817 44.188 44.730 46.241 46.545 46 .822 1.00 7.16 1.00 5.40 1.00 9.76 1.00 0.00 1.00 5.88 1.00 7.20 1.00 0.00 1.00 7.58 1.00 9.48 1.00 8.34 1.00 0.00 1.00 6.84 1.00 5.05 1.00 9.41 1.00 2.00 1.00 2.21 1.00 8.80 1.00 10.47 1.00 9.78 1.00 0.00 1.00 10.08 1.00 8.96 1.00 3.65 1.00 10.29 1.00 9.07 1.00 12.20 1.00 0.00 1.00 0.00 1.00 0.00 1.00 11.23 1.00 11.13 1.00 12.69 1.00 0.00 1.00 11.54 1.00 9.05 1.00 7.75 1.00 10.85 1.00 8.02 9 a 9 9*99** 156 ATOM 229 C LEU 26 12.016 14.770 42.709 1.00 13.09 0 0

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

230 O 231 N 232 H 233 CA 234 CB 235 C 236 O 237 N 238 H 239 CA 240 C 241 0 242 N 243 H 244 CA 245 CB 246 CG 247 A 248 CE 249 C 250 O 251 N 252 H 253 CA 254 CB 255 C 256 O 257 N 258 H 259 CA 260 CB 261 CG 262 OD1 263 OD2 264 C 265 O 266 N 267 H

LEU

ALA

ALA

ALA

ALA

ALA

ALA

GLY

GLY

GLY

GLY

GLY

SEM

SEM

SEM

SEM

SEM

SEM

SEM

SEM

SEM

ALA

ALA

ALA

ALA

ALA

ALA

ASP

ASP

ASP

ASP

ASP

ASP

ASP

ASP

ASP

GLY

GLY

13.194 10.998 10.076 11.207 10.114 11.310 11.450 11.214 11.100 11.322 10.059 10.121 8.911 8.916 7.633 7.691 6.357 5.628 4.244 7.244 6.551 7.661 8.158 7.361 8.328 5.920 5.336 5.345 5.870 3.967 3.556 3.270 3.279 3.023 3.822 4.678 2.727 2.082 14.788 14.768 14.716 14.809 14.036 16.217 16.388 17.228 17.075 18.588 19.417 20.638 18.764 17.783 19.461 20.394 20.714 19.139 20.250 20.262 21.277 19.799 18.959 20.506 20.078 20.303 19.246 21.323 22.127 21.251 22.553 23.682 24.850 23.415 20.110 19.920 19.371 19.548 42.353 1.00 13.85 41.852 1.00 14.57 42.182 1.00 0.00 40.409 1.00 14.74 39.690 1.00 11.97 39.847 1.00 14.47 38.637 1.00 18.58 40.701 1.00 14.44 41.663 1.00 0.00 40.208 1.00 16.06 40.277 1.00 18.17 40.125 1.00 20.12 40.445 1.00 18.95 40.530 1.00 0.00 40.560 1.00 19.29 41.774 1.00 26.13 42.386 1.00 38.67 43.253 1.00 56.20 43.984 1.00 49.18 39.307 1.00 17.59 39.404 1.00 14.79 38.132 1.00 17.50 38.095 1.00 0.00 36.883 1.00 17.68 35.787 1.00 17.19 36.427 1.00 18.58 36.667 1.00 20.12 35.786 1.00 19.30 35.608 1.00 0.00 35.287 1.00 18.84 34.585 1.00 22.71 35.550 1.00 26.71 35.109 1.00 32.54 36.744 1.00 30.87 34.298 1.00 15.55 33.434 1.00 13.41 34.413 1.00 13.36 35.121 1.00 0.00 0 00000 00000 157 ATOM 268 CA GLY 32 2.500 18.261 33.513 1.00 10.92 0 a a a a

C

a a.

a. a

C

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1 5 ATOM

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20 ATOM

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ATOM

ATOM

269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 :92 "9 3 294 295 296 297 298 299 300 301 302 303 304 305 306 C GLY O GLY N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N PHE H PHE CA PHE CB PHE CG PHE CDI PHE CD2 PHE CEl PHE CE2 PHE CZ PHE C PHE O PHE N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N LEU H LEU CA LEU CB LEU CG LEU CDI LEU 3.215 3.189 3.920 3.996 4.608 5.587 6.506 7.578 7.146 3.486 2.665 3.431 4.113 2.369 1.236 1.587 1.247 2.259 1.575 2.587 2.247 2.820 3.861 2 .015 1.189 2.294 3.228 2.861 1.822 4.125 0.950 -0.071 0.947 1.787 -0.266 -0.513 -1.945 -2.670 17.002 16.002 17.063 17.913 15.889 16.297 15.217 14.842 15.735 15.015 15.495 13.751 13.400 12.868 12.837 12.101 10.755 12.746 10.066 12.070 10.727 11.446 11.003 10.724 11.106 9.328 9.170 9.681 8.770 9.730 8.638 9.297 7.321 6.845 6.543 5.745 5.377 6.628 33.956 33.241 35.084 35.563 35.621 36.730 37.309 36.312 38.564 36.193 36.987 35.786 35.173 36.247 35.210 33.941 33.784 32.905 32.615 31.739 31.589 36.510 36.026 37.273 37.637 37.564 38.780 40.178 40.833 41.033 37.759 37.976 37.628 37.447 37.772 36.487 36.090 35.627 1.00 10.21 1.00 12.71 1.00 10.73 1.00 0.00 1.00 10.86 1.00 10.14 1.00 8.41 1.00 8.33 1.00 4.68 1.00 11.04 1.00 10.22 1.00 8.86 1.00 0.00 1.00 6 1.00 5.89 1.00 7.44 1.00 8.28 1.00 3 .28 1.00 10.52 1.00 5.20 1.00 7.45 1.00 6.42 1.00 7.20 1.00 5.42 1 00 0.00 1.00 5.16 1.00 3 .91 1.00 5.75 1.00 3 .81 1.00 5.45 1.00 5.01 1.00 4.17 1.00 5 .84 1.00 0.00 1.00 6.22 1.00 8.32 1.00 12.01 1.00 9 .93 158

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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ATOM

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15 ATOM

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20 ATOM

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25 ATOM

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307 308 309 310 311 312 313 314 315 316 317 318 319 CD2 LEU C LEU 0 LEU N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NH1 ARG 320 HH11 ARG 321 HH12 ARG 322 NH2 ARG 323 HH21 ARG 324 HH22 ARG 325 C ARG 326 o ARG 327 N GLN 328 H GLN 329 CA GLN 330 CB GLN 33 1 CC GLN 332 CD GLN 333 OEi GLN 334 NE2 GLN 335 HE21 GLN 336 HE22 GLN 337 C GLN 338 o GLN 339 N CYS 340 H CYS 341 CA CYS 342 CB CYS 343 SG CYS 344 C CYS 345 0 CYS 36 36 36 37 37 37 37 37 37 37 37 37 37 37 37 37 37 37 37 37 38 38 38 38 38 38 38 38 38 38 38 38 39 39 39 39 39 39 39 -1.924 -0.093 1.002 -1.156 -1.991 -1.122 -0.845 -1.713 -1.287 -1.942 -1.677 -2.891 -3.308 -2.923 -4.022 -3.400 -3.054 -4.109 -2.443 -3.387 -2 .496 -1.732 -3.708 -3 .356 -4.540 -4.101 -3.915 -3 .892 -4.078 -3.579 -4.649 -4.209 -5.938 -6.237 -6.933 -8.266 -9.520 -7.085 -7.116 4.333 5.587 5.075 5.396 5.875 4.469 5.190 6.381 7.057 8.346 9.086 8.584 7.614 6.697 7.812 9.798 10.515 9.997 3.732 4.105 2.657 2.444 1.858 0.428 -0.505 -1.914 -2.283 -2.698 -2.315 -3.605 2.483 2.975 2.477 2.044 3.049 3.168 4.051 2.150 0.921 34.975 38.942 39.178 39.712 39.531 40.837 42.156 42.403 43.664 43.828 43.246 44.719 45.526 45.464 46.194 44.824 44.228 45.488 40.884 40.195 41.652 42.213 41.758 42.169 42.289 42.594 43.750 41.555 40.666 41.714 42.772 43 .802 42.469 41.640 43.361 42.638 43 .539 44.577 44.451 1.00 11.40 1.00 5.04 1.00 4.23 1.00 5.30 1.00 0.00 1.00 4.66 1.00 3.66 1.00 2.00 1.00 2.41 1.00 2.04 1.00 0.00 1.00 3.03 1.00 2.03 1.00 0.00 1.00 0.00 1.00 2.00 1.00 0.00 1.00 0.00 1.00 3.21 1.00 4.62 1.00 5.11 1.00 0.00 1.00 8.69 1.00 9.37 1.00 12.33 1 .CO 16.53 1.00 20.00 1.00 19.17 1.00 0.00 1.00 0.00 1.00 8.28 1.00 11.23 1.00 8.89 1.00 0.00 1.00 8.08 1.00 5.67 1.00 10.90 1.00 9.83 1.00 7.19 159 ATOM 346 N LEU 40 -7.158 2.768 45.750 1.00 7.63

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9

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S

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20 ATOM

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347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU 0 LEU N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NHI ARG 365 HH11 ARG 366 HH12 ARG 367 NH2 ARG 368 HH21 ARG 369 HH22 ARG 40 40 40 40 40 40 40 40 41 41 41 41 41 41 41 41 41 41 41 41 41 41 41 41 41 42 42 42 42 42 42 42 42 43 43 43 43 -7.089 -7.310 -6.505 -4.997 -4.374 -4.388 -8.774 -9.115 -9.638 -9.326 -11.060 -11.519 -10.675 -11.147 -11.038 -10.148 -12.057 -13.280 -13.439 -14.048 -11.851 -10.937 -12.626 -11.990 -13.110 -11.550 -10.650 -12.389 -12.866 -11.774 -12.149 -11.651 -10.457 -12.381 -13.322 -11.795 -12.800 3.751 2.036 2.722 2.799 3.725 1.407 1.974 1.337 2.622 3.073 2.681 4.138 5.023 6.449 6.990 7.039 7.468 7.483 7.153 7.854 7.937 7.928 8.289 1.898 1.581 1.604 1.838 0.859 1.763 2.306 3.093 -0.349 -0.528 -1.209 -1.022 -2.400 -3.556 45.775 1.00 0.00 46.994 1.00 9.31 48.103 1.00 9.89 47.891 1.00 9.01 48.921 1.00 11.37 47.975 1.00 9.89 47.405 1.00 9.85 48.399 1.00 11.71 46.633 1.00 9.83 45.825 1.00 0.00 46.952 1.00 9.49 47.000 1.00 8.44 47.900 1.00 5.66 47.830 1.00 8.87 46.481 1.00 11.49 46.102 1.00 0.00 45.775 1.00 13.34 46.280 1.00 15.40 47.206 1.00 0.00 45.750 1.00 0.00 44.555 1.00 14.77 44.156 1.00 0.00 44.031 1.00 0.00 46.042 1.00 9.85 46.434 1.00 8.69 44.827 1.00 10.68 44.525 1.00 0.00 43.902 1.00 12.49 42.764 1.00 12.46 42.050 1.00 17.74 41.607 1.00 0.00 43.352 1.00 14.30 43.600 1.00 14.79 42.654 1.00 14.42 42.491 1.00 0.00 42.062 1.00 14.72 42.094 1.00 15.93 370 371 372 373 374 375 376 377 378 379 380 381 382 383

ARG

ARG

SER

SER

SER

SER

SER

SER

SER

SER

LEU

LEU

LEU

LEU

ATOM 384 CG LEU 43 -13.008 -4.241 43.445 1.00 17.87 160 S.

S

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15 ATOM

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20 ATOM

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385 CD1 LEU 386 CD2 LEU 387 C LEU 388 0 LEU 389 N GLY 390 H GLY 391 CA GLY 392 C GLY 393 O GLY 394 N GLY 395 H GLY 396 CA GLY 397 C GLY 398 O GLY 399 N TYR 400 H TYR 401 CA TYR 402 CB TYR 403 CG TYR 404 CD1 TYR 405 CE1 TYR 406 CD2 TYR 407 CE2 TYR 408 CZ TYR 409 OH TYR 410 HH TYR 411 C TYR 412 O TYR 413 N VAL 414 H VAL 415 CA VAL 416 CB VAL 417 CG1 VAL 418 CG2 VAL 419 C VAL 420 O VAL 421 N LEU 422 H LEU 423 CA LEU 43 -14.314 -5.017 43 43 43 44 44 44 44 44 45 45 45 45 45 46 46 46 46 46 46 46 46 46 46 46 46 46 46 47 47 47 47 47 47 47 47 48 48 48 -11.835 -11.390 -12.165 -10.148 -9.563 -9.646 -9.496 -9.353 -9.489 -9.551 -9.360 -7.943 -7.088 -7.705 -8.441 -6.389 -5.709 -5.371 -4.305 -4.046 -6.157 -5.905 -4.858 -4.640 -4.204 -6.548 -7.667 -5.429 -4.562 -5.440 -5.152 -5.289 -6.108 -4.333 -3.225 -4.672 -5.588 -3.720 -5.158 -2.091 -1.496 -2.418 -2.772 -2.186 -0.733 -0.434 0.170 -0.116 1.580 2.071 1.360 3.312 3.865 3.916 3.954 2.597 1.853 0.573 2.024 0.743 0.024 -1.262 -1.681 5.339 5.816 5.988 5.532 7.384 7.623 9.116 6.824 8.033 7.504 9.119 9.443 9.870 43.740 40.623 39.867 40.283 40.986 38.938 38.533 37.353 39.503 40.434 39.192 39.371 39.899 38.978 38.629 39.077 37.694 37.127 37.634 37.177 36.136 35.670 36.197 35.765 36.505 39.564 39.748 39.840 39.759 40.223 41.720 42.024 42.591 39.398 39.323 38.710 38.750 37.903 1.00 19.73 1.00 14.52 1.00 14.42 1.00 15.19 1.00 0.00 1.00 13.99 1.00 11.65 1.00 15.02 1.00 9.86 1.00 0.00 1.00 5.54 1.00 5.84 1.00 6.52 1.00 5.35 1.00 0.00 1.00 5.58 1.00 5.14 1.00 6.25 1.00 7.73 1.00 7.63 1.00 8.86 43.441 1.00 18.61 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 7.09 9.65 14.03 0.00 6.00 5.33 3.93 0.00 6.45 5.21 2.00 2.00 6.52 5.99 8.11 0.00 8.79 161 e.g.

C @0 C. C 0

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25 ATOM

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ATOM

424 425 426 427 428 429 430 431 432 433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 CB LEU CG LEU CD1 LEU CD2 LEU C LEU

LEU

N SEP.

H SER CA SER CB SEP.

OG SEP.

HG SER C SER

SER

LEU

H LEU CA LEU CE LEU CG LEU CD1 LEU CD2 LEU C LEU 0 LEU N VAL H VAL CA VAL CB VAL CG1 VAL CG2 VAL C VAL 0 VAL N HIS H HIS CA HIS CB HIS CG HIS CD2 HIS ND1 HIS HD1 HIS -4.418 -3 .677 -4.438 -2.240 -3.277 -4.102 -1.998 -1.392 -1.479 -0.683 -1.495 -1.674 -0.595 0.371 -0.951 -1.751 -0.170 -0.735 -2.127 -3 .182 -2.275 0.064 -0.663 1. 099 1 .613 1 .471 3 .000 3.369 3 .445 1.1ill 1.283 0.545 0.343 0.231 -1 .148 -1.460 -2 .483 -0.645 0.164 10.427 10.764 11.888 11. 183 11. 039 11.873 11.078 10.383 12.166 11. 611 10.791 10.001 13 .083 12 .625 14.363 14.686 15.315 15.498 15.995 15.206 17.479 16 .657 17.056 17.343 16.980 18.635 18.704 20.031 17.520 19.758 19.637 20. 823 20.832 22.005 21.937 23 .127 24.011 23.530 23.066 36.658 35.353 34.674 35.576 38.779 39.162 39.139 38.818 39.960 41. 144 41. 969 41. 438 39.108 38.498 39.031 39.502 38.252 36.827 36.426 37 .167 36.672 38.929 39.845 38.467 37.717 39.007 39.283 39.938 40 .138 38.046 36.833 38.591 39.556 37 .814 37 .167 36.308 36.344 35.269 34.951 1.00 12.43 1.00 14.11 1.00 14.34 1.00 10.17 1.00 11.50 1.00 9.63 1.00 11.61 1.00 0.00 1.00 8.18 1.00 7.55 1.00 3.18 1.00 0.00 1.00 9.13 1.00 10.70 1.00 10.96 1.00 0.00 1.00 12.63 1.00 16.12 1.00 17.82 1.00 23.32 1.00 17.92 1.00 11.83 1.00 8.52 1.00 10.51 1.00 0.00 1.00 10.18 1.00 9.58 1.00 5.85 1.00 8.60 1.00 10.79 1.00 11.95 1.00 10.19 1.00 0.00 1.00 13.16 1.00 16.99 1.00 19.12 1.00 19.25 1.00 21.39 1.00 0.00 0*0**0 0 0 162 S S SS S 0 0@ S *5 S

*OS*

S.

S S

S

ATOM 463 CEl HIS 52 ATOM 464 NE2 HIS 52 ATOM 465 HE2 HIS 52 ATOM 466 c HIS 52 ATOM 467 0 HIS 52 ATOM 468 N ASP 53 ATOM 469 H ASP 53 ATOM 470 CA ASP 53 ATOM 471 CB ASP 53 1 0 ATOM 472 CG ASP 53 ATOM 473 ODi ASP 53 ATOM 474 0D2 ASP 53 ATOM 475 C ASP 53 ATOM 476 0 ASP 53 15 ATOM 477 N VAL 54 ATOM 478 H VAL 54 ATOM 479 CA VAL 54 ATOM 480 CB VAL 54 ATOM 481 CG1 VAL 54 ATOM 482 CG2 VAL 54 ATOM 483 C VAL 54 ATOM 484 0 VAL 54 ATOM 485 N ARG 55 ATOM 486 H ARC 55 25 ATOM 487 CA ARC 55 ATOM 488 C3 ARG 55 ATOM 489 CG ARG 55 ATOM 490 CD ARG 55 ATOM 491 NE ARG 55 ATOM 492 HE ARC 55 ATOM 493 CZ ARG 55 ATOM 494 NH1 ARG 55 ATOM 495 Hll ARG 55 ATOM 496 HH12 ARG 55 ATOM .497 NH2 ARG 55 ATOM 498 FH21 ARC 55 ATOM 499 HH22 ARC 55 ATOM 500 C ARC 55 ATOM 501 0 ARC 55 -2.271 -2.880 0.285 -0.304 1.035 1.499 1.182 -0.156 -0.260 -0.918 0.314 1.709 1 .213 2.706 3 .064 3.298 4.081 4 .962 4.943 2.207 2 .325 1.180 1.149 0 .049 -1.166 -2.454 -2.330 -3.385 -4.305 -3 .179 -1.950 -1.181 -1.803 -4.204 -5.129 -4.061 -0.278 -0.162 24.919 25.642 23 .137 23 .033 24.186 24.235 25.341 26.062 27.272 27.174 28.321 24 .977 25.490 24.094 23 .729 23 .650 24.806 24.261 25.546 23 .094 23 .144 22.502 22.431 21.936 22.862 22.303 22.040 21.152 21.346 20.109 19.818 20.384 19 .025 19.345 19.569 18.561 20.539 20.289 35.335 35.070 38.813 39.884 38.487 37.643 39.370 39.523 38.643 37.586 39.016 40.753 41.759 40,803 39.964 42 .072 42 .777 43 .892 41.773 43 .004 44.234 42.399 41.425 43 .127 42.982 43 .543 45.036 45 .519 45.243 46.319 46.738 46.445 47 .333 46 .686 46.367 47.291 42 .586 41.386 1.00 20.49 1.00 0.00 1.00 14.35 1.00 14.87 1.00. 18.31 1.00 0.00 1.00 21.21 1.00 25.36 1.00 33.50 1.00 39.21 1.00 35.58 1.00 21.34 1.00 20.63 1.00 20.75 1.00 0.00 1.00 21.10 1.00 22.31 1.00 21.47 1.00 25.32 1.00 20.23 1.00 21.96 1.00 20.64 1.00 0.00 1.00 20.79 :.00 24.88 1.00 37.51 1.00 47.31 1.00 52.82 1.00 0.00 1.00 54.83 1.00 51.75 1.00 0.00 1.00 0.00 1.00 55.41 1.00 0.00 1.00 0.00 1.00 17.44 1.00 16.40 -1.154 24.607 34.702 1.00 18.57

SO

S. S 0 0058 0 0 0 00600S S S 163 ATOM 502 ATOM 503 ATOM 504 ATOM 505 ATOM 506 ATOM 507 ATOM 508 ATOM 509 ATOM 510 1 0 ATOM 511 ATOM 512 ATOM 513 ATOM 514 ATOM 515 1 5 ATOM 516 ATOM 517 ATOM 518 ATOM 519 ATOM 520 ATOM 521 ATOM 522 ATOM 523 ATOM 524 ATOM 525 25 ATOM 526 ATOM 527 ATOM 528 ATOM 529 ATOM 530 ATOM 531 ATOM 532 ATOM 533 ATOM 534 ATOM 535 ATOM 536 ATOM 537 ATOM 538 ATOM 539 ATOM 540

N

H

CA

CB

CG

CD1 CD2 CEl CE2

PHE

PE

PHE

PHE

PE

PE

PE

PE

PE

PE

PE

PE

HIS

H HIS CA HIS CB HIS CG HIS CD2 HIS ND1 HIS EDi HIS CEl HIS NE2 HIS HE2 HIS C HIS O HIS N HIS H HIS CA HIS CB HIS CG HIS CD2 HIS ND1 HIS EDi HIS CEl HIS NE2 HIS HE2 HIS C HIS 0 HIS N PHE -0.697 -0.795 -1.038 -0.670 0.767 1.134 1.756 2.468 3 .093 3 .449 -2.518 -3.354 -2.835 -2.116 -4.217 -4.550 -4.415 -3.346 -5.466 -6.378 -5.050 -3.770 -3.184 -4.288 -3 .451 -5.226 -5.837 -5.387 -5.236 -3 .964 -3 .707 -2.748 -2.585 -1.799 -2.354 -1.914 -6.734 -7 .773 -6.704 19.642 19.904 18.276 17.295 17.346 17.879 16.864 17.931 16.911 17.448 18.128 18.696 17.346 16.929 17.082 17.771 19.263 20.065 20.103 19 .803 21.356 21.361 22.148 15.567 14.981 14.932 15 .442 13.478 12.884 13.291 14.285 12.703 11.924 13 .318 14.281 14 .927 13 .130 13 .391 12.588 43.472 44.409 43.087 44. 192 44.596 45.828 43.751 46.213 44.126 45.362 42.806 43.502 41.786 41.249 41.405 40.076 40. 108 39.882 40.413 40.644 40.374 40.056 40. 028 41. 245 40.553 41.947 42.530 41.892 43.293 43 .973 44.855 43 .697 43.109 44.372 45.082 45.656 41.302 41.905 40.093 1.00 12.91 1.00 0.00 1.00 11.38 1.00 7.94 1.00 9.45 1.00 9.25 1.00 7.32 1.00 7.59 1.00 10.67 1.00 7.88 1.00 10.74 1.00 11.90 1.00 12.61 1.00 0.00 1.00 12.51 1.00 15.95 1.00 16.89 1.00 17.62 1.00 21.02 1.00 0.00 1.00 18.85 1.00 17.75 1.00 0.00 1.00 11.47 1.00 9.71 1.00 10.52 1.00 0.00 1.00 7.58 1.00 4.66 1.00 4.02 1.00 2.46 1.00 3.15 1.00 0.00 1.00 2.00 1.00 3.60 1.00 0.00 1.00 6.91 1.00 10.26 1.00 8.54 164

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 571.

572 573 574 575 576 577 578 579 H PHE 59 CA PHE 59 CB PHE 59 CG PHE 59 CD1 PHE 59 CD2 PHE 59 CEl PHE 59 CE2 PHE 59 CZ PHE 59 C PHE 59 O PHE 59 N PRO 60 CD PRO 60 CA PRO 60 CB PRO 60 CG PRO 60 C PRO 60 O PRO 60 N ILE 61 H ILE 61 CA ILE 61 CB ILE 61 CG2 ILE 61 CG. ILE 61 CD ILE 61 C ILE 61 O ILE 61 N GLU 62 H GLU 62 CA GLU 62 CB GLU 62 CG GLU 62 CD GLU 62 OE1 GLU 62 0E2 GLU 62 C GU 62 O GLU 62 N ARG 63 H ARG 63 -5.843 -7.907 -7.816 -7.752 -6.533 -8.913 -6.466 -8.856 -7.630 -8.126 -7.342 -9 .188 -10.180 -9 .444 -10.483 -11. 247 -9.983 -10.806 -9.457 -8.791 -9.857 -8.615 -9 .025 -7.715 -6.386 -10.651 -10.165 -11.883 -12.238 -12.723 -14.100 -14.963 -16.337 -17.320 -16.434 -12.884 -12.984 -12.867 -12.783 12 .465 12.202 12.653 14.138 14.796 14.881 16.181 16.263 16.915 10.703 9.932 10.263 11.018 8 .826 8.718 9.988 8.349 9.023 7.226 6.793 6. 625 6.239 5.656 7.460 7 .129 5.366 4.499 5.286 6.005 4.132 4.575 3 .422 3 .864 3 .612 4.450 3.230 3 .707 1.925 1.600 39.640 39.372 37.915 37.749 37.774 37.588 37.646 37.461 37.492 39.410 38.852 40.089 40.877 40.147 41.258 41.119 38.804 38.174 38.339 38.870 37 .079 36.246 34.906 36. 041 35.387 37.432 38.167 36.947 36.378 37.233 37.737 38.253 38.716 37.980 39.819 36.021 34.892 36.262 37.186 1.00 0.00 1.00 5.78 1.00 7.34 1.00 7.56 1.00 8.46 1.00 6.77 1.00 10.40 1.00 9.75 1.00 11.63 1.00 6.79 1.00 7.41 1.00 9.70 1.00 6.89 1.00 10.01 1.00 10.34 1.00 9.58 1.00 13.30 1.00 14.14 1.00 13.16 1.00 0.00 1.00 13.78 1.00 11.71 1.00 13.24 1.00 9.66 1.00 6.22 1.00 15.81 1.00 14.88 1.00 19.32 1.00 0.00 1.00 23.46 1.00 28.96 1.00 36.57 1.00 40.63 1.00 41.74 1.00 41.68 1.00 21.41 1.00 21.22 1.00 21.79 1.00 0.00 165

S

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 0 ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

584 585 586 587 588 589 590 591 592 593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 580 581 582 583 CA ARG 63 CB ARG 63 CG ARG 63 CD ARG 63 NE ARG 63 HE ARG 63 CZ ARG 63 NH1 ARG 63 HHII ARG 63 HH12 ARG 63 NH2 ARG 63 HH21 ARG 63 HH22 ARG 63 C ARG 63 O ARG 63 N GLN 64 H GLN 64 CA GLN 64 CB GLN 64 CG GLN 64 CD GLN 64 OE1 GLN 64 NE2 GLN 64 HE21 GLN 64 HE22 GLN 64 C GLN 64 O GLN 64 N LEU 65 H LEU 65 CA LEU 65 CE LEU 65 CG LEU 65 CD1 LEU 65 CD2 LEU 65 C LEU 65 O LEU 65 N ASN 66 H ASN 66 CA ASN 66 -13.036 -12.425 -12.414 -11.931 -12.828 -13.722 -12.516 -11.318 -10.639 -11.100 -13.406 -14.306 -13.189 -14.529 -15.218 -15.028 -14.402 -16.449 -16.757 -16.217 -16.893 -16.698 -17.681 -17.785 -18.122 -16.911 -16.117 -18 .215 -18.766 -18.834 -20.361 -21.194 -22.682 -20.861 -18.490 -18.406 -18.281 -18.363 -17.946 0.943 -0.391 -1.419 -2.760 -3.269 -2.876 -4.231 -4.806 -4.529 -5.528 -4.610 -4.173 -5.331 0.767 0.244 1.218 1.626 1.125 1.886 3.306 4.236 4.135 5.164 5.194 5.773 -0.318 -1.214 -0.523 0.242 -1.842 -1.731 -1.014 -1.210 0.477 -2.498 -3.720 -1.670 -0.709 -2.155 35.205 35.615 34.496 34.997 36.027 36.094 36.887 36.851 36.173 37.509 37.793 37.818 38.450 34.999 35.872 33.856 33.234 33.538 32.247 32.192 33 .175 34.384 32.655 31.683 33 .280 33 .385 33 .084 33 .551 33 .804 33 .428 33 .578 32.498 32.774 32.425 32 .089 31.988 31.070 31.237 29.735 1.00 25.45 1.00 27.80 1.00 33.00 1.00 33.41 1.00 35.94 1.00 0.00 1.00 35.92 1.00 37.94 1.00 0.00 1.00 0.00 1.00 36.87 1.00 0.00 1.00 0.00 1.00 26.74 1.00 29.01 1.00 29.10 1.00 0.00 1.00 32.01 1.00 31.94 1.00 35.07 1.00 36.14 1.00 36.71 1.00 40.49 1.00 0.00 1.00 0.00 1.00 35.23 1.00 36.40 1.00 39.04 1.00 0.00 1.00 41.57 1.00 45.35 1.00 48.79 1.00 48.80 1.00 48.69 1.00 40.88 1.00 41.06 1.00 40.78 1.00 0.00 1.00 39.66 166

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

619 CB ASN 620 CG ASN 621 ODi ASN 622 ND2 ASN 623 HD21 ASN 624 HD22 ASN 625 C ASN 626 0 ASN 627 N GLY 628 H GLY 629 CA GLY 630 C GLY 631 0 GLY 632 N THR 633 H THR 634 CA THR 635 CB THR 636 OGi TER 637 HG1 THR 638 CG2 THR 639 c THR 640 o THR 641 N TYR 642 H TYR 643 CA TYR 644 C3 TYP.

645 CG TYR 646 CD1 TYR 647 CEl TYR 648 CD2 TYR 649 CE2 TYR 650 CZ TYR 651 OH TYR 652 HH TYR 653 C TYR 654 0 TYR 655 N ALA 656 H ALA 657 CA ALA 66 66 66 66 66 66 66 66 67 67 67 67 67 68 68 68 68 68 68 68 68 68 69 69 69 69 69 69 69 69 69 69 69 69 69 69 70 70 70 -18.496 -18.333 -18.884 -17.605 -17.199 -17.532 -16.464 -16.045 -15.676 -16.031 -14.253 -13.349 -12.138 -13.923 -14.888 -13.128 -13.872 -15.186 -15.620 -13.957 -12.746 -13.144 -11.995 -11.718 -11.551 -10.047 -9.664 -9.485 -9.189 -9.533 -9.236 -9 .067 -8.785 -8.850 -11.897 -11.727 -12.361 -12.479 -12.725 -1.214 0 .255 0 .742 0.977 0.536 1 .927 -2.440 -2 .686 -2.408 -2 .213 686 -1.520 -1.697 -0.338 -0.234 0. 838 1.785 2.052 2.606 1.180 1.596 1.220 2. 678 2.938 3.483 3.328 1.936 0.934 -0.370 1.601 0.308 -0.674 -1.961 -2.067 4.936 5.468 5.591 5.142 6.991 28.649 28.995 29.987 28.161 27.388 28.370 29.505 28.375 30.577 31.465 30.467 30.106 29.991 29.904 29.971 29.574 28.620 29.127 28.472 27.230 30.838 31. 938 30.673 29.778 31.796 31.978 32.386 31.433 31.815 33.731 34.119 33.161 33.546 34.504 31. 583 30.487 32.638 33.508 32.533 1.0 1.0 1.0 1.0 1.01 1.0 1.0 1.00C 1.00C 1.00C 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1. 00 1.00 1.00 1.00 1 .00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0 43.14 0 46.18 0 48.62 0 45.77 0 0.00 0 0.00 236.70 35.57 35.06 0.00 32.41 30.31 30.24 28.66 0.00 25.46 26.78 27.70 0.00 27 .47 23 .00 22.61 20.59 0.00 15.58 12. 63 12 .79 10.68 13 9.78 11.49 11.48 13.55 0 .00 15.95 13.25 17 .69 0.00 19.16

ATOM

ATOM

ATOM

ATOM

ATOM

167 ATOM 658 CB ALA 70 -14.150 7.121 31.981 1.00 18 .87 ATOM 659 C ALA 70 -12.608 7.742 33.848 1.00 18 .59 ATOM 660 0 ALA 70 -12.844 7.184 34.925 1.00 19.11 ATOM 661 N ILE 71 -12.155 8.985 33.749 1.00 19.47 ATOM 662 H ILE 71 -11.906 9.337 32.870 1.00 0.00 ATOM 663 CA ILE 71 -12.048 9.864 34.897 1.00 19.95 ATOM 664 CB ILE 71 -11.037 10.989 34.645 1.00 21.71 ATOM 665 CG2 ILE 71 -11.010 11.948 35.814 1.00 20.85 ATOM 666 CG1 ILE 71 -9.644 10.405 34.428 1.00 21.25 ATOM 667 CD ILE 71 -8.597 11.453 34.109 1.00 23 ATOM 668 C ILE 71 -13.448 10.455 34.936 1.00 21.14 ATOM 669 0 ILE 71 -14.049 10.673 33.888 1.00 19.95 ATOM 670 N ALA 72 -13.991 10.669 36.126 1.00 25.60 *ATOM 671 H ALA 72 -13.484 10.472 36.937 1.00 0.00 1 5 ATOM 672 CA ALA 72 -15.335 11.220 36.240 1.00 30.18 :::ATOM 673 CB ALA 72 -15.679 11.495 37.698 1.00 31.23 ATOM 674 C ALA 72 -15.458 12.494 35.412 1.00 33.10 *ATOM 675 0 ALA 72 -14.651 i3.418 35.551 1.00 34.99 *ATOM 676 N GLY 73 -16.425 12.502 34.500 1.00 33 .63 ATOM 677 H GLY 73 -16.972 11.706 34.360 1.00 0.00 ATOM 678 CA GLY 73 -16.643 13.663 33.658 1.00 34.45 *ATOM 679 C GLY 73 -15.998 13.530 32.293 1.00 34.98 ATOM 680 0 GLY 73 -16.470 14.113 31.317 1.00 36.54 ATOM 681 N GLY 74 -14.931 12.743 32.221 1.00 34.48 25 ATOM 682 H GLY 74 -14.615 12.263 33 .010 1.00 0.00 ATOM 683 CA GLY 74 -14.230 12.558 30.966 1.00 32.55 ATOM 684 C GLY 74 -14.704 11.388 30.130 1.00 32.17 ATOM 685 0 GLY 74 -15.632 10.666 30.493 1.00 32.72 ATOM 686 N LYS 75 -14.040 11.200 28.997 1.00 31.90 ATOM 687 H LYS 75 -13.309 11.813 28.811 1.00 0.00 ATOM 688 CA LYS 75 -14.361 10.125 28.075 1.00 30.83 ATOM 689 CB LYS 75 -14.002 10.536 26.645 1.00 34.04 ATOM 690 CG LYS 75 -12.604 11.124 26.486 1.00 37.94 ATOM 691 CD LYS 75 -12.207 11.203 25.022 1.00 40.86 ATOM 692 CE LYS 75 -12.088 9.811 24.408 1.00 44.39 ATOM 693 NZ LYS 75 -11.678 9.850 22.977 1.00 46.69 ATOM 694 HZ1 LYS 75 -10.759 10.330 22.888 1.00 0.00 ATOM 695 HZ2 LYS 75 -12.394 10.355 22.419 1.00 0.00 ATOM 696 HZ3 LYS 75 -11.601 8.873 22.628 1.00 0.00 168 ATOM 697 C LYS 75 -13.652 8.825 28.443 1.00 29.70 ATOM 698 0 LYS 75 -12.567 8.840 29.035 1.00 29.72 ATOM 699 N ALA 76 -14.264 7.705 28.072 1.00 26.68 ATOM 700 H ALA 76 -15.096 7.775 27.566 1.00 0.00 ATOM 701 CA ALA 76 -13.711 6.388 28.352 1.00 26.38 ATOM 702 CB ALA 76 -14.813 5.334 28.327 1.00 26.29 ATOM 703 C ALA 76 -12.621 6.028 27.355 1.00 23.85 ATOM 704 0 ALA 76 -12.590 6.542 26.241 1.00 23.96 ATOM 705 N HIS 77 -11.718 5.149 27.769 1.00 23.92 ATOM 706 H HIS 77 -11.794 4.779 28.678 1.00 0.00 ATOM 707 CA HIS 77 -10.624 4.715 26.915 1.00 23.21 ATOM 708 CB HIS 77 -9.349 5.468 27.270 1.00 22.18 .ATOM 709 CG HIS 77 -9.466 6.947 27.097 1.00 22.49 ATOM 710 CD2 HIS 77 -9.273 7.732 26.012 1.00 23.47 1 ATOM 711 ND1 HIS 77 -9.870 7.784 28.111 1.00 25.61 :ATOM 712 HD1 HIS 77 -10.123 7.524 29.028 1.00 0.00 ATOM 713 CEl HIS 77 -9.920 9 .025 27.662 1.00 25.59 ATOM 714 NE2 HIS 77 -9.563 9.020 26.390 1.00 24.65 ATOM 715 HE2 HIS 77 -9.544 9.793 25.792 1.00 0.00 ATOM 716 C HIS 77 -10.413 3.227 27.073 1.00 23.54 ATOM 717 0 HIS 77 -10.833 2.640 28.067 1.00 22.48 *::*ATOM 718 N CYS 78 -9.762 2.622 26.086 1.00 24.06 ATOM 719 H CYS 78 -9.468 3 .146 25.315 1.00 0.00 ATOM 720 CA CYS 78 -9.500 1.186 26.089 1.00 25.49 25 ATOM 721 CB CYS 78 -8.831 0.762 24.782 1.00 28.48 ATOM 722 SG CYS 78 -9.718 1.274 23.311 1.00 45.92 ATOM 723 C CYS 78 -8.625 0.743 27.245 1.00 20.86 ATOM 724 0 CYS 78 -8.675 -0.413 27.649 1.00 21.75 ATOM 725 N GLY 79 -7.791 1.646 27.740 1.00 17.20 ATOM 726 H GLY 79 -7.750 2 .555 27.393 1.00 0.00 ATOM 727 CA GLY 79 -6.919 1.297 28.839 1.00 13.97 ATOM 728 C GLY 79 -6.204 2.501 29.408 1.00 13.22 ATOM 729 0 GLY 79 -6.291 3 .600 28.848 1.00 12.24 ATOM 730 N PRO 80 -5.473 2.314 30.518 1.00 14.67 ATOM 731 CD PRO 80 -5.345 1.022 31.222 1.00 16.84 ATOM 732 CA PRO 80 -4.714 3 .358 31.207 1.00 15.78 ATOM 733 CB PRO 80 -4.108 2.610 32.402 1.00 17.64 ATOM 734 CG PRO 80 -4.039 1.179 31.930 1.00 17.90 ATOM 735 C PRO 80 -3.645 3 .991 30.321 1.00 14.91 169 ATOM 736 O PRO 80 -3.434 5.206 30.357 1.00 15.49 ATOM 737 N ALA 81 -3.003 3.168 29.500 1.00 13.13 ATOM 738 H ALA 81 -3.231 2.212 29.488 1.00 0.00 ATOM 739 CA ALA 81 -1.969 3.645 28.594 1.00 13.20 ATOM 740 CB ALA 81 -1.325 2.474 27.882 1.00 11.11 ATOM 741 C ALA 81 -2.585 4.602 27.584 1.00 12.98 ATOM 742 O ALA 81 -2.080 5.706 27.376 1.00 9.81 ATOM 743 N GLU 82 -3.712 4.185 27.006 1.00 15.40 ATOM 744 H GLU 82 -4.074 3.319 27.268 1.00 0.00 ATOM 745 CA GLU 82 -4.432 4.975 26.007 1.00 16.50 ATOM 746 CB GLU 82 -5.578 4.165 25.391 1.00 18.83 ATOM 747 CG GLU 82 -5.143 3.076 24.417 1.00 22.18 ATOM 748 CD GLU 82 -4.391 1.934 25.087 1.00 29.04 ATOM 749 OE1 GLU 82 -4.960 1.286 25.992 1.00 29.04 15 ATOM 750 OE2 GLU 82 -3.228 1.678 24.702 1.00 36.49 ATOM 751 C GLU 82 -4.974 6.266 26.594 1.00 16.45 ATOM 752 O GLU 82 -5.064 7.287 25.905 1.00 15.38 ATOM 753 N LEU 83 -5.338 6.215 27.868 1.00 15.01 ATOM 754 H LEU 83 -5.252 5.365 28.350 1.00 0.00 ATOM 755 CA LEU 83 -5.863 7.378 28.567 1.00 13.23 ATOM 756 CB LEU 83 -6.453 6.957 29.920 1.00 11.92 ATOM 757 CG LEU 83 -7.191 8.010 30.748 1.00 9.05 ATOM 758 CD1 LEU 83 -8.321 7.365 31.526 1.00 6.47 ATOM 759 CD2 LEU 83 -6.217 8.729 31.669 1.00 8.09 25 ATOM 760 C LEU 83 -4.770 8.431 28.743 1.00 12.70 ATOM 761 O LEU 83 -4.964 9.603 28.415 1.00 13.58 ATOM 762 N CYS 84 -3.608 8.013 29.228 1.00 12.46 ATOM 763 H CYS 84 -3.484 7.068 29.473 1.00 0.00 ATOM 764 CA CYS 84 -2.508 8.948 29.419 1.00 11.61 ATOM 765 CB CYS 84 -1.387 8.289 30.207 1.00 10.43 ATOM 766 SG CYS 84 -1.915 7.860 31.867 1.00 10.33 ATOM 767 C CYS 84 -1.997 9.485 28.092 1.00 13.49 ATOM 768 O CYS 84 -1.591 10.640 28.003 1.00 12.47 ATOM 769 N GLU 85 -2.024 8.640 27.064 1.00 16.19 ATOM 770 H GLU 85 -2.346 7.726 27.199 1.00 0.00 ATOM 771 CA GLU 85 -1.590 9.035 25.729 1.00 18.26 ATOM 772 CB GLU 85 -1.542 7.812 24.802 1.00 19.98 ATOM 773 CG GLU 85 -0.393 6.843 25.144 1.00 26.96 ATOM 774 CD GLU 85 -0.462 5.465 24.456 1.00 28.02 170 ATOM 775 OE1 GLU 85 ATM 75 OE GU 50.570 4.759 24.466 1.00 25.08 ATOM 776 ATOM 777 ATOM 778 ATOM 779 ATOM 780 ATOM 781 ATOM 782 ATOM 783 1 0 ATOM 784 ATOM 785 ATOM 786 ATOM 787 ATOM 788 15ATOM 789 ATOM 790 ATOM 791 ATOM 792 ATOM 793 ATOM 794 ATOM 795 ATOM 796 ATOM 797 ATOM 798 25 ATOM 799 ATOM 800 ATOM 801 ATOM 802 ATOM 803 ATOM 804 ATOM 805 ATOM 806 ATOM 807 ATOM 808 ATOM 809 ATOM 810 ATOM 811 ATOM 812 ATOM 813 0E2 GLU C GLU 0 GLU N PE H PE CA PHE CB PE CG PHE CD1 PE CD2 PE CEl PE CE2 PE CZ PE C PE O PE N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CEl TYR CD2 TYR CE2 TYR CZ TYR OH TYR HE TYR C TYR o TYR N SER H SER CA SER CB SER OG SER HG SER C SER o SER N ARG -1.530 -2.537 -2 .099 -3 .824 -4.103 839 -6.240 -7 .350 -7.867 -7 .867 -8 .883 -8 .878 -9.387 -4 .674 -4 .705 -4.511 -4.518 -4.357 -4.645 106 -6.551 -7.911 -7 .056 -8.411 -8.834 -10.179 -10.601 -3 .042 -2.918 -2 .059 -2 .164 -0.775 0.258 0 .617 0 .973 -0.938 -0.278 -1 .822 5 .069 10.113 11.077 9.985 9.216 10.948 10.391 11.360 11.487 12.167 12-407 13.089 13.209 12.313 13.355 12.302 11.448 13 .542 13.303 13.035 11.781 11.519 14.028 13.780 12.526 12.284 13.151 14.282 15 .457 13.598 12 .641 14.222 13 .165 12.360 12.975 15.226 16.265 14.908 23.937 25.192 24.564 25.508 26.042 25.080 25.368 25.084 23.801 26.096 23.529 25.834 24.551 25.762 25.104 27.082 27 .562 27.838 29.316 29.553 29.964 30.142 29.327 29.500 29.907 30.070 29.992 27.629 27.988 27 .054 26.866 26.763 26.371 27 .480 28.143 25.619 25.595 24.677 1.00 27.13 1.00 19.29 1.00 22.26 1.00 18.82 1.00 0.00 1.00 15.74 1.00 14.90 1.00 17.05 1.00 20.88 1.00 17.90 1.00 21.36 1.00 16.83 1.00 20.44 1.00 15.39 1.00 9 .31 1.00 14.05 1.00 0.00 1.00 16.04 1.00 15.23 1.00 17.80 1.00 20.66 1.00 21.74 1.00 19.58 1.00 19.90 1.00 22.31 1.00 24.09 1.00 0.00 1.00 15.72 1.00 13.60 1.00 17.80 1.00 0.00 1.00 23 1.00 23.49 1.00 33.23 1.00 0.00 1.00 26.20 1.00 28.26 1.00 30.06 171 ATOM 814 H ARG 89 -2.342 14.080 24.761 1.00 0.00 555.

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

815 CA ARG 816 CB ARG 817 CG ARG 818 CD ARG 819 NE ARG 820 HE ARG 821 CZ ARG 822 NH1 ARG 823 HH11 ARG 824 HH12 ARG 825 NH2 ARG 826 HH21 ARG 827 HH22 ARG C ARG O ARG N ASP H ASP CA ASP CB ASP CG ASP OD1 ASP OD2 ASP C ASP O ASP N PRO CD PRO CA PRO CB PRO -2.070 -2.350 -1.112 -0.425 0.796 0.710 2.023 2.212 1.435 3.142 3.070 2.936 3.993 -3.224 -3.220 -4.206 -4.177 -5.370 -6.533 -7.780 -8.865 -7.688 -5.775 -6.160 -5.678 -5.144 -6.046 -5.938 -4.817 -7.479 -7.783 -8.358 -8.041 -9.768 -9.906 -11.281 -11.880 -11.748 15.771 14.931 14.334 13.287 12.767 12.040 13.219 14.212 14.633 14.533 12.664 11.899 13.004 16.747 17.849 16.342 15.460 17.181 16.707 17.576 17.075 18.749 17.137 16.086 18.280 19.571 18.363 19.860 20.280 17.869 17.169 18.287 18.890 17.895 16.470 16.192 15.142 17.009 23.524 22.269 21.598 22.464 21.848 21.193 22.103 22.967 23.434 23.154 21.503 20.870 21.690 23.742 23.195 24.539 24.968 24.797 23.907 24.028 23.662 24.464 26.271 26.784 26.974 26.500 28.391 28.677 27.793 28.576 29.536 27.664 26.966 27.660 27.097 26.498 26.826 25.679 1.00 33.80 1.00 37.17 1.00 43.59 1.00 47.19 1.00 51.34 1.00 0.00 1.00 53.00 1.00 53.42 1.00 0.00 1.00 0.00 1.00 54.73 1.00 0.00 1.00 0.00 1.00 33.93 1.00 35.37 1.00 34.09 1.00 0.00 1.00 32.55 1.00 34.44 1.00 37.74 1.00 42.07 1.00 36.32 1.00 31.21 1.00 29.06 1.00 31.00 1.00 31.27 1.00 30.53 1.00 30.79 1.00 30.18 1.00 30.82 1.00 32.23 1.00 31.25 1.00 0.00 1.00 29.68 1.00 32.25 1.00 33.34 1.00 33.77 1.00 39.38 CA ASP CB ASP CG ASP OD1 ASP OD2 ASP 172 ATOM 853 C ASP 92 -10.423 18.005 29.043 1.00 30.56 ATOM 854 ATOM 855 ATOM 856 ATOM 857 ATOM 858 ATOM 859 ATOM 860 ATOM 861 ATOM 862 ATOM 863 ATOM 864 ATOM 865 ATOM 866 ATOM 867 ATOM 868 ATOM 869 ATOM 870 ATOM 871 20 ATOM 872 ATOM 873 ATOM 874 ATOM 875 ATOM 876 ATOM 877 ATOM 878 ATOM 879 ATOM 880 ATOM 881 ATOM 882 ATOM 883 ATOM 884 ATOM 885 ATOM 886 ATOM 887 ATOM 888 ATOM 889 ATOM 890 E ATOM 891 F

O

N

H

CA

C

O

N

H

CA

CB

CG

CD1 CD2

C

O

N

CD

CA

CB

CG

C

0

N

H

CA

ASP

GLY

GLY

GLY

GLY

GLY

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

PRO

PRO

PRO

PRO

PRO

PRO

PRO

CYS

CYS

CYS

CYS

CYS

CYS

CYS

ASN

92 93 93 93 93 93 94 94 94 94 94 94 94 94 94 95 95 95 95 95 95 95 96 96 96 96 96 96 96 97 97 97 97 97 97 97 97 97 -11.208 -10.099 -9.464 -10.665 -9.654 -9.933 -8.488 -8.329 -7.451 -6.353 -6.696 -5.403 -7.429 -6.830 -6.927 -6.175 -6.077 -5.526 -4.898 -5.821 -4.456 -4.073 -3.924 -4.197 -2.911 -1.580 -0.785 -2.715 -3.114 -2.145 -1.833 -1.919 -1.613 -0.384 -0.267 0.540 0.370 1.350 17.142 19.079 19.737 19.285 19.345 19.912 18.737 18.255 18.741 17.725 16.241 15.473 15.742 20.133 20.942 20.423 19.560 21.715 21.518 20.556 22.009 23.163 20.944 20.035 21.022 21.563 20.559 19.626 18.633 19.547 20.360 18.259 18.432 19.271 20.381 18.754 17.869 19.270 29.442 29.762 29.417 31.084 32.218 33.278 32.020 31.183 33.046 32.710 32.594 32.399 33.829 33.167 32.239 34.310 35.502 34.558 35.939 36.598 33.504 33.301 32.909 33.153 31.859 32.394 33.655 31.285 31.897 30.092 29.642 29.464 27.978 27.734 28.255 26.936 26.542 26.774 1.00 30.28 1.00 29.01 1.00 0.00 1.00 27.68 1.00 27.53 1.00 28.17 1.00 25.94 1.00 0.00 1.00 26.33 1.00 22.36 1.00 22.65 1.00 20.32 1.00 21.91 1.00 27.78 1.00 27.47 1.00 26.98 1.00 26.89 1.00 26.62 1.00 24.83 1.00 24.86 1.00 27.96 1.00 29.86 1.00 27.78 1.00 0.00 1.00 26.63 1.00 29.10 1.00 33.00 1.00 25.83 1.00 25.07 1.00 24.09 1.00 0.00 1.00 24.47 1.00 27.75 1.00 30.72 1.00 33.88 1.00 32.61 1.00 0.00 1.00 0.00 H ASN CA ASN CB ASN CG ASN OD1 ASN ND2 ASN 1D21 ASN ID22 ASN 173 ATOM 892 C ASN 97 -0.779 17.526 30.154 1.00 22.90

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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ATOM

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ATOM

ATOM

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25 ATOM

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ATOM

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ATOM

ATOM

893 894 895 896 897 898 899 900 901 902 903 904 905 906 907 908 909 910 911 912 O ASN N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NH1 ARG 97 98 98 98 98 98 98 98 98 98 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99 100 100 100 100 100 100 100 100 100 100 100 0.056 -0.756 -1.447 0.273 -0.201 -1.503 -1.847 -1.368 1.568 1.685 2.545 2.399 3.815 4.261 3.230 3.620 2.530 1.868 2.366 3.224 4.000 3.111 1.342 0.700 1.238 4.961 5.461 5.377 4.912 6.507 7.575 8.939 9.891 11.321 11.443 10.853 11.123 12.438 18.140 16.207 15.800 15.369 13.913 13.668 12.182 14.215 15.498 14.970 16.180 16.534 16.425 17.864 18.899 20.296 21.243 21.026 22.383 22.733 22.139 23.583 23.177 22.940 24.034 15.471 14.789 15.408 15.896 14.564 15.441 14.799 15.784 15.259 13.994 13.266 14.155 13.683 30.820 29.990 29.429 30.591 30.641 31.417 31.440 32.828 29.790 28.683 30.372 31.271 29.712 29.974 29.558 29.990 29.758 29.067 30.426 31.380 31.586 31.889 30.139 29.416 30.643 30.022 29.125 31.281 31.993 31.644 32.304 32.507 33.196 33.266 34.043 33.597 35.017 34.047 1.00 21.51 1.00 20.54 1.00 0.00 1.00 19.00 1.00 14.90 1.00 11.64 1.00 6.04 1.00 9.37 1.00 20.67 1.00 22.82 1.00 20.51 1.00 0.00 1.00 21.55 1.00 19.71 1.00 22.45 1.00 25.64 1.00 31.98 1.00 0.00 1.00 35.95 1.00 38.13 1.00 0.00 1.00 0.00 1.00 35.02 1.00 0.00 1.00 0.00 1.00 23.55 1.00 28.87 1.00 21.07 1.00 0.00 1.00 18.54 1.00 20.05 1.00 27.37 1.00 29.35 1.00 32.53 1.00 36.81 1.00 0.00 1.00 0.00 1.00 0.00 9 913 HH11 ARG 914 HH12 ARG 915 NH2 ARG 916 HH21 ARG 917 HH22 ARG 918 919 920 921 922 923 924 925 926 927 928 929 930 C ARG O ARG N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS 174 ATOM 931 ATOM 932 ATOM 933 ATOM 934 ATOM 935 ATOM 936 ATOM 937 ATOM 938 ATOM 939 1 0 ATOM 940 ATOM 941 ATOM 942 ATOM 943 ATOM 944 1 5 ATOM 945 ATOM 946 ATOM 947 ATOM 948 ATOM 949 ATOM 950 ATOM 951 ATOM 952 ATOM 953 C LYS O LYS N PRO CD PRO CA PRO CB PRO CG PRO C PRO O PRO N CYS H CYS CA CYS CB CYS SG CYS C CYS O CYS N ASN H ASN CA ASN CB ASN CG ASN OD1 ASN ND2 ASN 100 100 101 101 101 101 101 '101 101 102 102 102 102 102 1-02 102 103 103 103 103 103 103 103 103 1.03 :03 J03 104 104 104 104 104 104 104 104 104 104 104 104 6.118 5.586 6.302 6.627 5.961 6.092 5.849 .6.987 8.194 6.510 5.550 7.410 6.762 7 .925 7.714 7.078 8.662 9.085 9 .073 10.013 9.374 8.206 10.132 11.054 9.730 9.741 10.513 9.448 8.826 10.018 9.501 8.089 7.691 7.262 6.380 8.001 9.227 9 .608 9.771 13 .410 13 .627 12.162 11.735 11.006 9.830 10.453 10 .883 10.987 10.718 10.658 10.576 11.078 11.184 9 097 8.364 8.661 9.330 7.264 7 .041 7.399 7 .101 8.056 8 .272 8.327 6 .767 7 .483 5 .522 5 .010 4.896 3.464 3 .354 1.901 1.324 1.537 0.529 0.203 0.548 -0.406 32.563 33.647 32.104 30.734 32.937 31. 965 30.620 34.064 33 .832 35.287 35.443 36.415 37.700 39.064 36.511 37.266 35.693 35.108 35.632 34. 444 33.124 32.888 32.259 32.491 31.394 36.899 37.537 37.247 36.697 38.426 38.556 39.074 39.222 37.951 37.599 37.190 37.557 38.418 36.979 1.00 17.15 1.00 16.18 1.00 16.34 1.00 15.63 1.00 16.36 1.00 16.00 1.00 17.99 1.00 15.83 1.00 14.18 1.00 14.78 1.00 0.00 1.00 12.30 1.00 8.52 1.00 12.86 1.00 13 .33 1.00 13.67 1.00 13.67 1.00 0.00 1.00 14.10 1.00 15.80 1.00 18.98 1.00 19.82 1.00 24.80 1.00 0.00 1.00 0.00 1.00 13 1.00 14.29 1.00 13.40 1.00 0.00 1.00 14.48 1.00 14.01 1.00 11.01 1.00 13 .56 1.00 18.89 1.00 0.00 1.00 16.72 1.00 24.48 1.00 0.00 1.00 0.00

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

954 HD21 ASN 955 HD22 ASN 956 C ASN 957 0 ASN 958 N ARG 959 H ARG 960 CA ARG 961 CS ARG 962 CG ARG 963 CD ARG 964 NE ARG 965 HE ARG 966 CZ ARG 967 NH1 ARG 968 HH11 ARG 969 HH12 ARG 175 ATOM 970 NH2 ARG 104 7.501 0.044 36.065 1.00 24.27

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

971 972 973 974 975 976 977 978 979 980 981 982 983 984 985 986 987 988 989 990 991 992 993 994 995 996 997 998 999 1000 1001 1002 1003 1004 1005 1006 1007 1008 HH21 ARG 104 HH22 ARG 104 C ARG 104 O ARG 104 N PRO 105 CD PRO 105 CA PRO 105 CB PRO 105 CG PRO 105 C PRO 105 O PRO 105 N SER 106 H SER 106 CA SER 106 CB SER 106 OG SER 106 HG SER 106 C SER 106 O SER 106 N GLY 107 H GLY 107 CA GLY 107 C GLY 107 O GLY 107 N LEU 108 H LEU 108 CA LEU 108 CB LEU 108 CG LEU 108 CD1 LEU 108 CD2 LEU 108 C LEU 108 O LEU 108 N GLU 109 H GLU 109 CA GLU 109 CB GLU 109 CG GLU 109 6.570 8.060 11.545 12.128 12.211 11.622 13.674 13.933 12.713 14.174 13.493 15.348 15.851 15.893 17.306 17.273 16.759 15.904 16.301 15.433 15.089 15.391 14.041 13.837 13.130 13.318 11.800 11.375 10.061 10.151 9.749 10.831 10.848 10.022 10.052 9.041 9.231 10.625 0.279 -0.560 4.871 4.542 5.235 5.709 5.248 5.750 6.566 3.816 2.884 3.629 4.400 2.283 2.329 2.524 3.302 1.572 2.154 0.330 -0.065 -0.420 -0.345 -0.989 0.462 1.005 0.577 2.044 2.277 1.672 3.758 -0.173 -0.020 -1.027 -1.102 -1.824 -3.310 -3.868 35.777 35.497 38.363 37.326 39.473 40.738 39.548 40.970 41.285 39.403 39.829 38.805 38.484 38.652 38.074 36.673 36.439 40.002 41.017 40.015 39.190 41.252 41.941 42.971 41.406 40.610 41.986 42.127 42.885 44.270 42.985 41.087 39.865 41.699 42.673 40.975 41.306 40.997 1.00 0.00 1.00 0.00 1.00 17.95 1.00 16.59 1.00 21.58 1.00 24.11 1.00 24.61 1.00 25.94 1.00 26.77 1.00 26.84 1.00 29.03 1.00 29.28 1.00 0.00 1.00 31.72 1.00 34.84 1.00 42.09 1.00 0.00 1.00 31.31 1.00 32.32 1.00 27.87 1.00 0.00 1.00 27.05 1.00 26.16 1.00 26.25 1.00 25.02 1.00 0.00 1.00 22.01 1.00 20.37 1.00 19.84 1.00 20.62 1.00 19.42 1.00 22.30 1.00 22.42 1.00 23.39 1.00 0.00 1.00 21.29 1.00 28.00 1.00 34.55 176 ATOM 1009 CD ATOM 1010 QEl ATOM 1011 0E2 *go* 0 9

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1012 1013 1014 1015 1016 1017 1018 1019 1020 1021 1022 1023 1024 1025 1026 1027 1028

C

0

N

CD

CA

CB

CG

C

0

N

H

CA

CB

CG

CD

OE1( NE2 GLU 109 GLU 109 GLU 109 GLU 109 GLU 109 PRO 110 PRO 110 PRO 110 PRO 110 PRO 110 PRO 110 PRO 110 GLN i11 GLN 111 GLN ill GLN 111 GLN 111 3LN i11 ;LN 111 ;LN 111 3LN 111 ;LN 11l ;LN il1 ;LN 111 ?RO 112 ~RO 112 ~RO 112 ~RO 112 ~RO 112 'RO 112 'RO 112 ;LY 113 LY 113 ;LY 113 ;LY 113 LY 113 AL 114 rAL 114 AL 114 11. 018 11. 970 10.378 7.655 7.516 6.619 6.595 5.274 4.405 5.315 4.988 5.280 4.451 4.224 4.146 3 .914 3.460 4.507 5.675 4.096 3 .152 4.763 2.921 1.858 3.064 4.324 1.962 2.616 4.043 0.818 1.044 -0.406 -0.506 -1.585 -1.920 -2.178 -1.964 -1.759 -2.325 1029 HE21C 1030 HE22C 1031 c C 1032 0 C 1033 N 1034 cD i 1035 CA 1 1036 CB 1 103'7 CG 1 1038 c 1 1039 0 1 1040 N C 1041 H G 1042 CA C 1043 c G 1044 0 C 1045 N 1046 H 1047 CA -4.363 -1.385 -0.686 -1.718 -2.348 -1.316 -1.856 -1.825 -2.029 -3 .213 -1.293 -0.362 -1.817 -0.630 -0.972 -1.733 -1.338 -2.841 -3.094 -3.331 -2.732 -2.337 -3.980 -4.595 -4.954 -6.176 -6.060 -4 .424 -3.924 -4.590 -5.038 -4.095 -4.452 -3.564 -5.742 -6.328 -6.279 38.737 42.357 42.503 43.320 43 .128 44.644 45.588 46.992 47 .779 47.828 48.393 48.292 48.921 44.631 44.164 45 .117 45.571 45 .169 45.814 45.391 46.036 47.140 45.550 44.681 46.242 47 .682 48.492 47 .985 47 .241 49 .308 1.00 9.71 1.00 13.59 1.00 15.70 1.00 14.83 1.00 0.00 1.00 14.80 1.00 19.62 1.00 29.16 1.00 35.22 1.00 39.00 1.00 38.02 1.00 0.00 1.00 0.00 1.00 13.55 1.00 13.13 1.00 15.54 1.00 14.21 1.00 14.46 1.00 17.80 1.00 18.52 1.00 12.81 1.00 13.23 1.00 13.74 1.00 0.00 1.00 16.62 1.00 20.03 1.00 25.17 1.00 15.08 1.00 0.00 1.00 15.99 -3.719 39.536 1.00 39.08 -2.955 39.253 1.00 41.37 38.672 1.00 40.88 41.414 1.00 17.67 42.420 1.00 17.75 40.628 1.00 13.39 39.301 1.00 8.68 41.038 1.00 11.28 39.912 1.00 9.37 177 0*S to**

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1048 1049 1050 1051 1052 1053 1054 1055 1056 1057 1058 1059 1060 1061 1062 1063 1064 1065 1066 1067 1068 1069 1070 1071 1072 1073 1074 1075 1076 1077 1078 1079 1080 1081 1082 1083 1084 1085 CB VAL CG1 VAL CG2 VAL C VAL 0 VAL N PE H PE CA PE CB PE CG PHE CD1 PE CD2 PHE CEl PE CE2 PHE CZ PHE C PE O PHE N ASP H ASP CA ASP CB ASP CG ASP ODi ASP 0D2 ASP C ASP O ASP N CLE H CLE CA CLE CB CLE SG CLE B CLE C CLE O CLE N LEU H LEU CA LEU CB LEU 114 114 114 114 114 115 115 115 115 115 115 115 115 115 115 115 115 116 116 116 116 116 116 116 116 116 117 117 117 117 117 117 117 117 118 118 118 118 -2.159 -2.735 -0.691 -3 .759 -4.000 -4.694 -4.473 -6.065 -7.021 -8.474 -8.900 -9.423 -10.253 -10.781 -11.197 -5.997 -6.553 -5.287 -4.943 -5.120 -4.240 -4.968 -6.205 -4.287 -4.466 -5.308 -5 .944 -5.029 -6.788 -7.960 -5.956 -5.029 -6.429 -5.316 -5.719 -6.745 -5.046 -7.090 -5.382 -6.405 -7.464 -8.548 -7.128 -6.208 -8.048 -7.420 -6.372 -6.246 -5.679 -9.347 50.525 51. 787 50.785 49.208 49.493 48.749 48.516 48.583 48.167 48.214 49.054 47.451 49.141 47. 528 48.376 47.471 47.592 46.398 46.326 45.272 44.181 43.349 43.445 42.569 45.740 45.344 46.593 46.841 47.135 47.962 48.533 50 .024 47.971 47.899 48.753 48.794 49.579 50.711 52 .027 1.00 15.66 1.00 15.95 1.00 18.12 1.00 14.14 1.00 15.64 1.00 12.08 1.00 0.00 1.00 8.80 1.00 6.19 1.00 3.76 1.00 2.76 1.00 6.51 1.00 5.06 1.00 6.67 1.00 6.27 1.00 9.14 1.00 12.04 1.00 9.44 1.00 0.00 1.00 12.42 1.00 15.62 1.00 19.07 1.00 23.47 1.00 25.14 1.00 11.75 1.00 11.50 1.00 12.80 1.00 0.00 1.00 14.11 1.00 16.88 1.00 22.90 1.20 31.80 1.00 16.15 1.00 17.64 1.00 15.34 1.00 0.00 1.00 13.10 1.00 12.53 1.00 17.96 -4.862 -10.445 -3.461 -9.199 -3.267 -8.285 -2.717 -10.321 -1.552 -9.797 -0.415 -11.054 1.110 -9.552 -3.607 -11.241 -3.484 -12.466 -4.509 -10.653 -4.574 -9.678 -5.419 -11.430 -5.994 -10.574 -5.204 -10.607 ATOM 1086 CG LEU 118 178 ATOM 1087 CD1 LEU 118 -3.763 -10.149 5185 .0 2.7 51.845 1.00 20.79 ATOM 1088 CD2 LEU 118 -5.915 -9.758 53.078 1.00 21.05 ATOM 1089 C LEU 118 -6.530 -12.068 48.744 1.00 13.66 ATOM 1090 0 LEU 118 -6.899 -13.220 48.977 1.00 13.82 ATOM 1091 N ARG 119 7.043 -11.343 47.752 1.00 13.95 ATOM 1092 H ARG 119 -6.729 -10.431 47.595 1.00 0.00 ATOM 1093 CA ARG 119 -8.097 -11.890 46.891 1.00 16.99 ATOM 1094 CB ARG 119 -8.685 -10.835 45.952 1.00 18.77 ATOM 1095 CG ARG 119 -9.292 -9.633 46.630 1.00 21.75 ATOM 1096 CD ARG 119 -10.186 -8.859 45.671 1.00 24.22 ATOM 1097 NE ARG 119 -9.634 -8.710 44.325 1.00 25.20 ATOM 1098 HE ARG 119 -9.753 -9.441 43.686 1.00 0.00 ATOM 1099 CZ ARG 119 -8.970 -7.644 43.889 1.00 26.62 **ATOM 1100 NH1 ARG 119 -8.751 -6.613 44.692 1.00 26.88 15 ATOM 1101 HH11 ARG 119 -9.079 -6.630 45.637 1.00 0.00 **ATOM 1102 HH12 ARG 119 -8.258 -5.813 44.357 1.00 0.00 ATOM 1103 NH2 ARG 119 -8.552 -7.596 42.632 1.00 28.12 ATOM 1104 HH21I ARG 119 -8.731 -8.366 42.018 1.00 0.00 *ATOM 1105 HH22 ARG 119 055 -6.793 42.296 1.00 0.00 ATOM 1106 c ARG 119 -7.573 -13.042 46.050 1.00 16.34 *e.*ATOM 1107 0 ARG 119 -8.338 -13.911 45.649 1.00 20.19 ATOM 1108 N ASP 120 -6.279 -13.038 45.747 1.00 16.82 ATOM 1109 H ASP 120 -5.712 -12.290 46.047 1.00 0.00 ATOM 1110 CA ASP 120 -5.699 -14.123 44.963 1.00 16.01 ATOM 1111 CB ASP 120 -4.195 -13.924 44.775 1.00 20.39 ATOM 1112 CG ASP 120 -3.543 -15.068 43.997 1.00 26.16 ATOM 1113 ODi ASP 120 -3.897 -15.260 42.813 1.00 29.33 ATOM 1114 0D2 ASP 120 -2.682 -15.778 44.570 1.00 25.10 ATOM 1115 C ASP 120 -5.972 -15.449 45.668 1.00 12.54 ATOM 1116 0 ASP 120 -6.566 -16.346 45.084 1.00 13.46 ATOM 1117 N ALA 121 -5.572 -15.539 46.935 1.00 10.31 ATOM 1118 F ALA 121 -5.115 -14.768 47.334 1.00 0.00 ATOM 1119 CA ALA 121 -5.764 -16.738 47.758 1.00 11.07 ATOM 1120 C B ALA 121 -5.155 -16.521 49.141 1.00 9.11 ATOM 1121 C ALA 121 -7.237 -17.132 47.903 1.00 9.94 ATOM 1122 0 ALA 121 -7.585 -18.311 47.927 1.00 13.51 ATOM 1123 N SEN 122 -8.103 -16.140 48.016 1.00 9.68 ATOM 1124 H SEN 122 -7.771 -15.218 48.000 1.00 0.00 ATOM 1125 CA SEN 122 -9.519 -16.402 48.163 1.00 11.81 179 ATOM 1126 CB SEM 122 -10.233 -15.133 48.605 1.00 19.02 ATOM 1127 CG SEM 122 -9.687 -14.587 49.905 1.00 29.28 ATOM 1128 A SEM 122 -10.585 -13.021 50.550 1.00 42.69 ATOM 1129 CE sEM 122 -9.376 -12.528 51.958 1.00 36.95 ATOM 1130 C SEM 122 -10.151 -16.974 46.903 1.00 9.90 ATOM 1131 0 SEM 122 -11.056 -17.804 46.988 1.00 10.61 ATOM 1132 N VAL 123 -9.693 -16.526 45.737 1.00 10.83 ATOM 1133 H VAL 123 -8.993 -15.829 45.711 1.00 0.00 ATOM 1134 CA VAL 123 -10.223 -17.029 44.471 1.00 10.83 1 0 ATOM 1135 CB VAL 123 -9.796 -16.144 43.277 1.00 11.82 ATOM 1136 CC1 VAL 123 -10.149 -16.814 41.957 1.00 13.10 *ATOM 1137 CG2 VAL 123 -10.489 -14.799 43.358 1.00 12.23 ATOM 1138 C VAL 123 -9.740 -18.469 44.269 1.00 11.72 ::.ATOM 1139 0 VAL 123 -10.492 -19.332 43.820 1.00 11.90 1~ ATOM 1140 N ARG 124 -8.496 -18.737 44.645 1.00 11.15 ::*ATOM 1141 H ARG 124 -7.934 -18.012 44.992 1.00 0.00 ATOM 1142 CA ARC 124 -7.952 -20.078 44.521 1.00 10.74 ATOM 1143 CB ARC 124 -6.496 -20.113 44.958 1.00 13.48 ATOM 1144 CG ARG 124 -5.588 -19.228 44.150 1.00 22.67 ATOM 1145 CD ARC 124 -4.164 -19.371 44.639 1.00 30.29 *ATOM 1146 NE ARC 124 -3.677 -20.737 44.462 1.00 34.80 **ATOM 1147 HE ARC 124 -3.798 -21.375 45.202 1.00 0.00 ATOM 1148 CZ ARC 124 -3.075 -21.173 43.359 1.00 36.89 ATOM 1149 NH1 ARC 124 -2.885 -20.352 42.330 1.00 35.72 ATOM 1150 HH11 ARC 124 -3.203 -19.404 42.371 1.00 0.00 ATOM 1151 HH12 ARC 124 -2.428 -20.690 41.503 1.00 0.00 ATOM 1152 NH2 ARC 124 -2.646 -22.427 43.292 1.00 38.58 ATOM 1153 HH21 ARC 124 -2.777 -23.034 44.072 1.00 0.00 ATOM 1154 HH22 ARC 124 -2.190 -22.758 42.469 1.00 0.00 ATOM 1155 C ARC 124 -8.750 -20.989 45.426 1.00 9.71 ATOM 1156 0 ARC 124 -9.144 -22.079 45.029 1.00 10.87 ATOM 1157 N ASP 125 -9.004 -20.526 46.644 1.00 11.13 ATOM 1158 H ASP 125 -8.663 -19.644 46.891 1.00 0.00 ATOM 1159 CA ASP 125 -9.753 -21.311 47.617 1.00 10.38 ATOM 1160 CB ASP 125 -9.765 -20.600 48.974 1.00 13.20 ATOM 1161 CC ASP 125 -10.489 -21.397 50.051 1.00 18.39 ATOM 1162 ODi ASP 125 -11.393 -20.831 50.706 1.00 21.49 ATOM 1163 0D2 ASP 125 -10.158 -22.590 50.238 1.00 18.02 ATOM 1164 C ASP 125 -11.174 -21.617 47.140 1.00 8.61 180 0

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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ATOM

15 ATOM

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ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1165 1166 1167 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 1180 1181 1182 1183 1184 1185 1186 1187 1188 1189 1190 1191 1192 1193 1194 1195 1196 1197 1198 1199 1200 1201 1202

CB

CG

CD1 CEl CD2 CE2 Cz

OH

HH

C

0

N

H

CA

TYR

TYR

TYR

TYR

TYR

TYR

TYR

TYR

TYR

TYR

TYR

VAL

VAL

VAL

0 ASP N TYR H TYR CA TYR CB VAL CG1 VAL CG2 VAL C VAL

VAL

N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NH1 ARG 125 126 126 126 126 126 126 126 126 126 126 126 126 126 126 127 127 127 127 127 127 127 127 128 128 128 128 128 128 128 128 128 128 128 128 128 128 128 -11.652 -22.741 -11.840 -20.621 -11.410 -19.747 -13.198 -20.802 -13.780 -19.452 -15.206 -19.523 -16.275 -19.332 -17.589 -19.395 -15.488 -19.784 -16.812 -19.856 -17.858 -19.655 -19.173 -19.702 -19.739 -19.596 -13.248 -21.776 -14.131 -22.629 -12.318 -21.618 -11.653 -20.905 -12.272 -22.469 -11.275 -21.918 -11.230 -22.826 -11.684 -20.512 -11.941 -23.916 -12.527 -24.843 -11.022 -24.112 -10.583 -23.335 -10.640 -25.450 -9.422 -25.365 -8.887 -26.701 -7.521 -26.528 -7.551 -25.528 -8.319 -25.519 -6.614 -24.606 -5.557 -24.541 -5.461 -25.186 -4.855 -23.840 -6.742 -23.746 -7.528 -23.786 -6.015 -23.087 -11.806 -26.118 47.266 46.579 46.499 46.074 45.641 45.138 46.009 45.562 43.794 43.334 44.228 43.806 44.573 44.888 44.815 43.948 44.039 42 .764 41.712 40.480 41.302 43.115 42.560 44.052 44.470 44.473 45.388 45.848 46.483 47.544 48.151 47.732 46.929 46.170 47.078 48.729 49.343 48.879 45.196 1.00 11.19 1.00 10.44 1.00 0.00 1.00 11.59 1.00 11.23 1.00 12.70 1.00 14.14 1.00 17.06 1.00 13.43 1.00 15.60 1.00 16.20 1.00 16.29 1.00 0.00 1.00 13.13 1.00 11.60 1.00 13.17 1.00 0.00 1.00 13.56 1.00 13.44 1.00 14.23 1.00 10.59 1.00 14.89 1.00 16.19 1.00 15.44 1.00 0.00 1. 00 15.05 1.00 19.03 1.00 24.57 1.00 29.44 1.00 32.78 1.00 0.00 1.00 32.41 1.00 28.66 1.00 0.00 1.00 0.00 1.00 34.68 1.00 0.00 1.00 0.00 1.00 16.91 HH1 1 HH1 2 NH2 HH21I HIH2 2

ARG

ARG

ARG

ARG

ARG

ATOM 1203 C AP.G 128 181 ATOM 1204 0 ARG 128 -12.185 -27.241 44.884 1.00 16.06

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1205 1206 1207 1208 1209 1210 1211 1212 1213 1214 1215 1216 1217 1218 1219 1220 1221 1222 1223 1224 1225 1226 1227 1228 1229 1230 1231 1232 1233 1234 1235 1236 1237 1238 1239 1240 1241 1242 N GLN H GLN CA GLN CB GLN CG GLN CD GLN OE1 GLN NE2 GLN HE21 GLN HE22 GLN C GLN O GLN N THR H THR CA THR CB THR OGI THR HG1 THR CG2 THR C THR O THR N TRP H TRP CA TRP CB TRP CG TRP CD2 TRP CE2 TRP CE3 TRP CD1 TRP NE1 TRP HE1 TRP CZ2 TRP CZ3 TRP CH2 TRP C TRP O TRP N LYS 129 129 129 129 129 129 129 129 129 129 129 129 130 130 130 130 130 130 130 130 130 131 131 131 131 31 131 131 131 131 131 :31 131 131 131 131 131 132 -12.025 -13.516 -13.922 -15.184 -15.850 -16.998 -15.134 -14.232 -15.573 -14.707 -15.374 -14.967 -14.422 -16.094 -16.473 -16.680 -17.352 -17.748 -15.909 -16.746 -14.812 -14.156 -14.551 -13.790 -14.586 -15. 383 -16.037 -15. 610 -14.773 -15.650 -15.968 -16.907 -16.477 -17.114 -13.852 -13. 892 -13.245 -24.508 -25.886 -24.813 -25.116 -23.854 -23.547 -23.120 -23.402 -22.317 -26.215 -27.227 -25.359 -24.549 -25.547 -24.207 -23.223 -23.533 -24.347 -26.599 -27.481 -26.507 -25 .807 -27 .429 -26.702 -25.559 -25.551 -24.299 -26.483 -24.339 -23.583 -22.696 -23.952 -26.137 -24.880 -28.712 -29.692 -28.710 -12-386 -25.399 46.149 46.347 46.924 47.941 48.735 49.274 48.934 50.124 50.371 50.462 46.024 46.202 45.051 44.954 44.151 43.491 44.513 45.132 42.666 43.063 42.894 42.329 42.510 41.235 40.128 39.589 38.398 38.342 37.375 40.183 39.444 39.715 37.301 36.340 36.312 41.629 40.883 42.813 1.00 17.04 1.00 0.00 1.00 17.75 1.00 24.23 1.00 35.10 1.00 43.22 1.00 45.61 1.00 44.34 1.00 0.00 1.00 0.00 1.00 14.94 1.00 17.51 1.00 12.68 1.00 0.00 1.00 14.74 1.00 16.50 1.00 15.75 1.00 0.00 1.00 16.34 1.00 14.23 1.00 15.79 1.00 13.82 1.00 0.00 1.00 12.96 1.00 13.33 1.00 15.21 1.00 16.02 1.00 16.98 1.00 19.06 1.00 16.24 1.00 19.42 1.00 0.00 1.00 17.20 1.00 19.80 1.00 18.84 1.00 1.00 1.00 13.29 12.51 15.49 182

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1243 1244 1245 1246 1247 1248 1249 1250 1251 1252 1253 1254 1255 1256 1257 1258 1259 1260 1261 1262 1263 1264 1265 1266 1267 1268 1269 1270 1271 1272 1273 1274 1275 1276 1277 1278 1279 1280 H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS O LYS N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU OE2 GLU C GLU O GLU N GLY H GLY CA GLY C GLY O GLY N GLU H GLU 132 132 132 132 132 132 132 132 132 132 132 132 133 133 133 133 133 133 133 133 133 134 134 134 134 134 134 134 134 134 134 135 135 135 135 135 136 136 -13.261 -12.531 -13.467 -14.374 -31.116 -15.519 -30.137 -16.482 -30.273 -15.842 -29.954 -15.472 -28.987 -15.060 -30.615 -16.535 -30.033 -11.310 -30.220 -10.973 -31.392 -10.635 -29.195 -10.915 -28.292 -9.459 -29.383 -9.539 -28.464 -10.724 -28.710 -10.779 -27.638 -10.608 -30.091 -8.158 -29.131 -8.137 -28.456 -7.068 -29.675 -7.120 -30.201 -5.758 -29.501 -5.418 -30.687 -6.137 -30.693 -5.572 -29.689 -6.063 -29.681 -4.643 -28.916 -4.694 -29.361 -4.968 -29.569 -3.494 -28.965 -3.374 -28.756 -2.392 -28.807 -2.686 -27.917 -3.416 -26.927 -2.149 -28.302 -1.609 -29.117 -2.324 -27.544 -27.900 -29.872 -31.090 43.361 43.344 43.451 44.670 44.557 45.727 47.029 47.004 47.195 47.800 42.496 42.325 41.991 42.231 41.149 39.930 38.993 37.930 38.365 41.897 42.921 41.372 40.549 41.983 42.899 44.262 45.276 46.427 44.940 40.904 39.719 41.316 42.265 40.382 39.189 39.297 38.035 38.031 36.799 i.00 0.00 1.00 18.55 1.00 17.43 1.00 19.61 1.00 21.76 1.00 20.70 1.00 23.81 00 0.00 1.00 0.00 1.00 0.00 1.00 20.84 1.00 21.28 1.00 22.03 1.00 0.00 1.00 23.93 1.00 22.92 1.00 21.45 1.00 16.33 1.00 18.90 1.00 25.56 1.00 24.95 1.00 30.15 1.00 0.00 1.00 35.39 1.00 40.72 i 00 47.74 1.00 52.02 1.00 52.20 1.00 54.41 1.00 35.44 1.00 35.63 1.00 34.91 1.00 0.00 1.00 34.73 1.00 34.52 1.00 34.03 1.00 34.50 1.00 0.00 1.00 34.12 ATOM 1281 CA GLU 136 183

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1282 1283 1284 1285 1286 1287 1288 1289 1290 1291 1292 1293 1294 1295 1296 1297 1298 1299 1300 1301 1302 1303 1304 1305 1306 1307 1308 1309 1310 1311 1312 1313 1314 1315 1316 1317 1318 1319 CB GLU CG GU CD GU OE1 GLU 0E2 GU C GLU O GLU N ALA H ALA CA ALA CB ALA C ALA O ALA N LEU H LEU CA LEU CB LEU CG LEU CD1 LET) CD2 LET) C LET) O LET) N GLU H GLU CA GLU CB GLU CG GLU CD GLU QEl GLU 0E2 GLT) C GLU o GLU N GLN H GLN CA GLN CB GLN CG GLN CD GLN 136 136 136 136 136 136 136 137 137 137 137 137 137 138 138 138 138 138 138 138 138 138 139 139 139 139 139 139 139 139 139 139 140 140 140 140 140 140 -1.543 -28.203 -1.203 -27.256 -0.456 -26.009 0.595 -26.145 -0.930 -24.889 -3.787 -27.359 -4.148 -26.351 -4.625 -28.329 -4.285 -29-104 -6.048 -28.258 -6.740 -29.548 -6.652 -27.072 -7.442 -26.317 -6.241 -26.894 -5.577 -27.514 -6.725 -25.792 -6.223 -25-941 -6.519 -24.807 -8.013 -24.543 -5.986 -25.170 -6.243 -24.469 -7.027 -23.528 -4.965 -24.415 -4.423 -25.227 -4.372 -23.209 -2.914 -23.454 -2.052 -23.944 -2.216 -23.110 -2.506 -23.697 -2.062 -21.872 -5.138 -22.737 -5.462 -21.555 -5.434 -23.669 -5.140 -24.594 -6.172 -23.361 -6.270 -24.605 -4.935 -25.155 -5.088 -26.459 -4.434 -27.461 35.658 34.511 34.980 35.650 34.686 36. 399 35.787 36.756 37.238 36.440 36.842 37.181 36.622 38.432 38.813 39.249 40.686 41.670 41. 738 43 .040 38.659 38.513 38.288 38.393 37.713 37.334 38.479 39.733 40.796 39.662 36.487 36.362 35.588 35.755 34.369 33.479 32.994 32.218 32 .523 1.00 38.90 1.00 43.32 1.00 46.70 1.00 48.76 1.00 46.11 1.00 31.34 1.00 28.55 1.00 29.45 1.00 0.00 1.00 26.31 1.00 26.49 1.00 22.29 1.00 22.04 1.00 20.21 1.00 0.00 1.00 20.63 1.00 17.38 1.00 17.34 1.00 16.71 1.00 15.22 1.00 21.98 1.00 21.24 1.00 23.87 1.00 0.00 1.00 25.73 1.00 28.07 1.00 33.00 1.00 37.06 1.00 41.81 1.00 39.33 1.00 26.80 1.00 25.34 1.00 29.70 1.00 0.00 1.00 31.92 1.00 38.06 1.00 45.35 1.00 52.31 1.00 54.99 ATOM 1320 OE1 GLN 140 184 ATOM 1321 NE2 GLN 140 -5.958 -26.453 31.212 1.00 53.53 ATOM 1322 HE21 GLN 140 -6.453 -25.632 31.016 1.00 0.00 ATOM 1323 HE22 GLN 140 -6.057 -27.290 30.723 1.00 0.00 ATOM 1324 c GLN 140 -7.579 -22.853 34.690 1.00 30.17 ATOM 1325 o GLN 140 -8.068 -21.914 34.058 1.00 29.36 ATOM 1326 N ALA 141 -8.218 -23.472 35.680 1.00 28.89 ATOM 1327 H ALA 141 -7.777 -24.201 36.166 1.00 0.00 ATOM 1328 CA ALA 141 -9.572 -23.099 36.084 1.00 27.36 ATOM 1329 CB ALA 141 -10.154 -24.143 37.028 1.00 25.84 1 0 ATOM 1330 c ALA 141 -9.665 -21.711 36.709 1.00 26.93 ATOM 1331 0 ALA 141 -10.584 -20.963 36.396 1.00 25.78 ATOM 1332 N ILE 142 -8.725 -21.358 37.581 1.00 27.95 ATOM 1333 H ILE 142 -8.010 -22.001 37.791 1.00 0.00 **ATOM 1334 CA ILE 142 -8.771 -20.043 38.209 1.00 30.29 1 5 ATOM 1335 CB ILE 142 -7.703 -19.856 39.321 1.00 32.16 ATOM 1336 CG2 ILE 142 -7.763 -21.010 40.310 1.00 31.60 ATOM 1337 CG1 ILE 142 -6.303 -19.742 38.722 1.00 38.22 ATOM 1338 CD ILE 142 -5.205 -19.539 39.750 1.00 41.97 ATOM 1339 C ILE 142 -8.628 -18.955 37.153 1.00 30.56 ATOM 1340 0 ILE 142 -9.256 -17.911 37.253 1.00 32.19 ATOM 1341 N ILE 143 -7.847 -19.223 36.111 1.00 31.49 ATOM 1342 H ILE 143 -7.382 -20.088 36.069 1.00 0.00 ATOM 1343 CA ILE 143 -7.656 -18.246 35.044 1.00 32.26 ATOM 1344 CiB ILE 143 -6.618 -18.736 34.000 1.00 34.28 ATOM 1345 CG2 ILE 143 -6.480 -17.728 32.868 1.00 34.40 ATOM 1346 CG1 ILE 143 -5.254 -18.975 34.661 1.00 36.63 ATOM 1347 CD ILE 143 -4.561 -17.724 35.179 1.00 39.46 ATOM 1348 C ILE 143 -8.984 -17.951 34.342 1.00 30.93 ATOM 1349 0 ILE 143 -9.295 -16.799 34.052 1.00 30.08 ATOM 1350 N SER 144 -9.776 -18.989 34.100 1.00 30.90 ATOM 1351 H SER 144 -9.524 -19.901 34.367 1.00 0.00 ATOM 1352 CA SER 144 -11.056 -18.826 33.427 1.00 33.20 ATOM 1353 CE SER 144 -11.434 -20.123 32.704 1.00 35.30 ATOM 1354 OG SER 144 -11.353 -21.242 33 .569 1.00 40.36 ATOM 1355 HG SER 144 -11.540 -22.026 33.050 1.00 0.00 ATOM 1356 c SER 144 -12.197 -18.375 34.343 1.00 34.38 ATOM 1357 o SER 144 -13.103 -17.653 33 .920 1.00 34.88 ATOM 1358 N GLN 145 -12.154 -18.803 35.598 1.00 34.59 ATOM 1359 H GLN 145 -11.420 -19.393 35.855 1.00 0.00 185 ATOM 1360 CA GLN 145 -13.189 -18.444 36.557 1.00 33.70

S

S.

S *5 S

*SSS

S

*SS*

S

S

ATOM 1361 ATOM 1362 ATOM 1363 ATOM 1364 ATOM 1365 ATOM 1366 ATOM 1367 ATOM 1368 ATOM 1369 ATOM 1370 ATOM 1371 ATOM 1372 ATOM 1373 1 5 ATOM 1374 ATOM 1375 ATOM 1376 ATOM 1377 ATOM 1378 ATOM 1379 ATOM 1380 ATOM 1381 ATOM 1382 ATOM 1383 ATOM 1384 ATOM 1385 ATOM 1386 ATOM 1387 ATOM 1388 ATOM 1389 ATOM 1390 ATOM 1391 1 ATOM 1392 F ATOM 1393 3 5 ATOM 1394 ATOM 1395 ATOM 1396 ATOM 1397 ATOM 1398 CB GLN 145 CG GLN 145 CD GLN 145 OE1 GLN 145 NE2 GLN 145 HE21 GLN 145 HE22 GLN 145 C GLN 145 O GLN 145 N ALA 146 H ALA 146 CA ALA 146 CB ALA 146 C ALA 146 O ALA 146 N PRO 147 CD PRO 147 CA PRO 147 CB PRO 147 CG PRO 147 C PRO 147 O PRO 147 N GLN 148 H GLN 148 CA GLN 148 CB GLN 148 CG GLN 148 CD GLN 148 OE1 GLN 148 NE2 GLN 148 1E21 GLN 148 1E22 GLN 148 C GLN 148 O GLN 148 N VAL 149 H VAL 149 CA VAL 149 CB VAL 149 -13.383 -13.934 -15.369 -15.699 -16.238 -15.932 -17.171 -12.948 -13.905 -11.687 -10.979 -11.343 -9.858 -12.199 -12.710 -12.371 -11.711 -13.178 -13.108 -11.741 -14.627 -15.170 -15.232 -14.719 -16.627 -17.194 -17.002 -17.614 -16.915 -18.925 -19.440 -19.303 -16.892 -17.963 -15.924 -15.084 -16.084 -15.730 -19.572 -20.859 -20.728 -21.098 -20.227 -19.964 -20.156 -17.124 -16.450 -16.735 -17.277 -15.500 -15.167 -14.278 -13.607 -13.970 -14.566 -12.812 -12.872 -13.432 -12.823 -11.781 -14.005 -14.803 -14.155 -15 .465 -15.634 -14.499 -13.779 -14.330 -14.926 -13.595 -14.083 -13.645 -14.518 -14.843 -14.506 -15.874 37.571 36.978 36.503 35.374 37.374 38.263 37.086 37.292 37.668 37.463 37.078 38.179 38.003 37.841 38.742 36.543 35.365 36.145 34.621 34.380 36.632 37.008 36.662 36.413 37.072 36.507 34.996 34.198 33.482 34.319 34.897 33.801 38.581 39.018 39.378 38.983 40.824 41.424 1.00 33.70 1.00 35.74 1.00 37.42 1.00 39.84 1.00 38.81 1.00 0.00 1.00 0.00 1.00 32.75 1.00 33.82 1.00 32.02 1.00 0.00 1.00 34.00 1.00 32.05 1.00 35.44 1.00 36.48 1.00 36.46 1.00 36.36 1.00 35.69 1.00 37.74 1.00 37.31 1.00 35.01 1.00 34.92 1.00 34.44 1.00 0.00 1.00 36.11 1.00 40.50 1.00 43.75 1.00 47.86 1.00 49.23 1.00 49.03 1.00 0.00 1.00 0.00 1.00 34.17 1.00 34.12 1.00 30.55 1.00 0.00 1.00 27.34 1.00 26.70 186 U* 1 5 ATOM 1399 ATOM 1400 ATOM 1401 ATOM 1402 ATOM 1403 ATOM 1404 ATOM 1405 ATOM 1406 ATOM 1407 ATOM 1408 ATOM 1409 ATOM 1410 ATOM 1411 ATOM 1412 ATOM 1413 ATOM 1414 ATOM 1415 ATOM 1416 ATOM 1417 ATOM 1418 ATOM 1419 ATOM 1420 ATOM 1421 ATOM 1422 ATOM 1423 ATOM 1424 ATOM 1425 ATOM 1426 ATOM 1427 ATOM 1428 ATOM 1429 ATOM 1430 ATOM 1431 ATOM 1432 ATOM 1433 ATOM 1434 ATOM 1435 ATOM 1436 ATOM 1437 CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU O GLU N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS 0 LYS N LEU H LEU CA LEU CB LEV CG LEU CD1 LEU CD2 LEU

VAL

VAL

GLU

GLU

CG1 VAL CG2 VAL 149 149 149 149 150 150 150 150 150 150 150 150 150 150 151 151 151 151 151 151 151 151 151 151 151 151 151 152 152 152 152 152 152 152 152 152 153 153 153 -15 .220 -14.622 -14.683 -13 .795 -13.249 -11. 848 -11.772 -12 .480 -10.981 -14.585 -14.179 -15.721 -15.998 -16.552 -17.721 -17.297 -16.749 -15.910 -14.684 -14.965 -14.135 -14.080 -17.064 -16.935 -17.620 -17 .693 -18.147 -18.532 -18.958 -20.324 -18.993 -17.113 -17 .408 -15.896 -15.725 -14.817 -13 .341 -12.565 -12.695 -11.477 -10.616 -10.013 -8.484 -7.918 -7.850 -10.600 -10.415 -10.083 -10.281 -9 .225 -8.646 -7.656 -6.357 -5 .572 -6.337 -7.218 -6.581 -5.784 -9.945 -9.430 -11.139 -11.501 -11.936 -13.336 -14.382 -14.025 -15.771 -12.059 -11.798 -12.436 -12.621 -12.595 -16.628 -16.942 -14.271 -16.202 -15.258 -13.418 40.829 41. 164 41. 506 42.732 40.708 39.739 41. 229 40.078 40. 336 40.177 39.313 40.915 42.201 43.344 41.749 40. 831 42.584 41.784 40.698 41. 293 40.282 39.897 39.418 40.747 39.256 43.820 44.925 43.633 42. 726 44.741 44.249 45.287 45.859 44.648 45.856 47.023 45.482 44. 531 46.441 1.00 27.05 1.00 25.34 1.00 27.10 1.00 26.82 1.00 27.77 1.00 0.00 1.00 28.17 1.00 32.48 1.00 42.10 1.00 43.81 1.00 41.18 1.00 45.59 1.00 24.18 1.00 22.05 1.00 21.94 1.00 0.00 1.00 22.44 1.00 25.52 1.00 33.26 1.00 36.27 1.00 36.61 1.00 38.17 1.00 0.00 1.00 0.00 1.00 0.00 1.00 20.52 1.00 21.76 1.00 18.37 1.00 0.00 1.00 17.20 1.00 18.20 1.00 23.16 1.00 21.89 1.00 22.05 1.00 15.24 1.00 14.43 1.00 12.34 1.00 0.00 1.00 13.12 187 ATOM 1438 CB ILE 153 -13.580 -13.261 4572 10 1.8 45.792 1.00 12.78 ATOM 1439 CG2 ILE 153 -12.498 -13.469 46.813 1.00 10.18 ATOM 1440 CG1 ILE 153 -13.962 -14.611 45.182 1.00 13.04 ATOM 1441 CD ILE 153 -14.603 -15.557 46.135 1.00 12.82 ATOM 1442 C ILE 153 -14.418 -11.265 47.081 1.00 12.71 ATOM 1443 0 ILE 153 -14.266 -11.189 48.297 1.00 14.81 ATOM 1444 N ALA 154 -14.299 -10.212 46.276 1.00 11.61 ATOM 1445 H ALA 154 -14.478 -10.311 45.317 1.00 0.00 ATOM 1446 CA ALA 154 -13.914 -8.897 46.789 1.00 11.24 1 0 ATOM 1447 CB ALA 154 -13.702 -7.932 45.643 1.00 8.04 ATOM. 1448 C ALA 154 -14.918 -8.308 47.788 1.00 11.11 ATOM 1449 0 ALA 154 -14.547 -7.850 48.872 1.00 8.33 ATOM 1450 N THR 155 -16.192 -8.345 47.432 1.00 11.93 **ATOM 1451 H THR 155 -16.462 -8.779 46.599 1.00 0.00 1 5 ATOM 1452 CA THR 155 -17.232 -7.793 48.285 1.00 16.85 ATOM 1453 CB THR 155 -18 .566 -7.654 47.509 1.00 19.45 ATOM 1454 OGi THR 155 -19.034 -8.949 47.108 1.00 23.26 *ATOM 1455 HG1 THR 155 -19.810 -8.856 46.545 1.00 0.00 ATOM 1456 CG2 THR 155 -18.366 -6.795 46.261 1.00 19.86 ATOM 1457 c THR 155 -17.450 -8.583 49.578 1.00 17.70 999ATOM 1458 0 THR 155 -18.015 -8.059 50.545 1.00 16.86 ATOM 1459 N THR 156 -16.945 -9.812 49.622 1.00 17.24 .9.ATOM 1460 H THR 156 -16.483 -10.203 48.844 1.00 0.00 ATOM 1461 CA THR 156 -17.110 -10.641 50.805 1.00 16.73 S 25 ATOM 1462 CB THR 156 -17.781 -11.991 50.436 1.00 18.95 ATOM 1463 OGI THR 156 -18.349 -12.579 51.610 1.00 28.41 ATOM 1464 HG1 THR 156 -17.628 -12.777 52.224 1.00 0.00 ATOM 1465 CG2 TER 156 -16.782 -12.958 49.825 1.00 16.01 ATOM 1466 c THR 156 -15.818 -10.864 51.607 1.00 15.60 ATOM 1467 0 TER 156 -15.853 -11.468 52.681 1.00 14.74 ATOM 1468 N ALA 157 -14.712 -10.291 51.134 1.00 11.48 ATOM 1469 H ALA 157 -14.745 -9.796 50.286 1.00 0.00 ATOM 1470 CA ALA 157 -13.404 -10.426 51.780 1.00 9.54 ATOM 1471 CB ALA 157 -12.342 -9.713 50.961 1.00 5.51 ATOM 1472 C ALA 157 -13.312 -9.981 53.239 1.00 8.69 ATOM 1473 0 ALA 157 -12.471 -10.476 53.987 1.00 10.31 ATOM 1474 N HIS 158 -14.150 -9.037 53.648 1.00 10.04 ATOM 1475 H HIS 158 -14.761 -8.654 52.995 1.00 0.00 ATOM 1476 CA HIS 158 -14.119 -8.550 55.029 1.00 9.74 188

C.

C C

C

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1477 1478 1479 1480 1481 1482 1483 1484 1485 1486 1487 1488 1489 1490 1491 1492 1493 1494 1495 1496 1497 1498 1499 1500 1501 1502 1503 1504 1505 1506 1507 1508 1509 1510 1511 1512 1513 1514 1515

CB

CG

CD2 ND1 HD1 CEl NE2 HE2

C

0

N

H

CA

CB

CG

CD

OE1 OE2

C

0

N

H

CA

CB

CG

CD

NE

HE

CZ

NH1 HHI 1 HH12 NH2 HH21 HH2 2

C

0

N

H

C

CC

C

C

HIS

HIS

HIS

HIS

HIS

HIS

HIS 158 HIS 158 HIS 158 HIS 158 GLU 159 GLU 159 GLU 159 GLU 159 GLU 159 GLU 159 GLU 159 GLU 159 GLU 159 GLU 159 ARG 160 ARG 160 ARG 160 ARG 160 ARG 160 ARG 160 ARG 160 ARG 160 ARG 160 ARG 160 ARG 160 ARG 160 ARG -160 ARG 160 ARG 160 ARG 160 ARG 160 SEM 161 SEM 161 -15.043 -16.494 -17.508 -17.045 -16.621 -18.336 -18.641 -19.542 -14.463 -13.948 -15.292 -15.604 -15.734 -16.826 -18.109 -19.133 -18.923 -20.157 -14.648 -14.881 -13.480 -13.336 -12.380 -11.637 -12.539 -11.737 -11.157 -10.278 -11.735 -12.907 -13.373 -13.329 -11.177 -10.326 -11.612 -11.407 -10.500 -11.610 -12.394 -7.335 -7.631 -7.875 -7.685 -7.506 -7.952 -8.073 -8.310 -9.621 -9.602 -10.580 -10.612 -11.657 -12.477 -11.703 -12.516 -13.733 -11.933 -12.601 -13.388 -12.552 -11.921 -13.428 -13.926 -14.448 -15.149 -16.394 -16.359 -17.585 -17.705 -16.903 -18.607 -18.647 -18.543 -19.546 -12. 697 -13.298 -11.391 -10.969 55.185 54.940 55.801 53.677 52.814 53.771 55.052 55.393 56.070 57.189 55.673 54.744 56.554 55.870 55.586 54.811 54.614 54.396 57.041 57.958 56.413 55.678 56.799 55.555 54.449 53.364 53.856 54.280 53.744 53.141 52.774 53.067 54.308 54.826 54.229 57.711 58.284 57.841 57.430 1.00 8.60 1.00 10.37 1.00 6.93 1.00 9.52 1.00 0.00 1.00 8.21 1.00 7.61 1.00 0.00 1.00 11.48 1.00 12.15 1.00 12.68 1.00 0.00 1.00 16.34 1.00 19.60 1.00 22.36 1.00 25.59 1.00 27.02 1.00 30.21 1.00 17.61 1.00 19.13 1.00 18.47 1.00 0.00 1.00 20.02 1.00 23.13 1.00 29.15 1.00 34.59 1.00 37.25 1.00 0.00 1.00 39.25 1.00 40.34 1.00 0.00 1.00 0.00 1.00 43.48 1.00 0.00 1.00 0.00 1.00 18.50 1.00 17.09 1.00 18.54 1.00 0.00 189 ATOM 1516 CA SEM 161 -10.746 -10.5505.61 .01.8 58.651 1.00 16.58

S

*5 S *5 S S *5 S S

S.

S S *5

*SS*

S

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1517 1518 1519 1520 1521 1522 1523 1524 1525 1526 1527 1528 1529 1530 1531 1532 1533 1534 1535 1536 1537 1538 1539 1540 1541 1542 1543 1544 1545 1546 1547 1548 1549 1550 1551 1552 1553 1554 CB SEM CG SEM A SEM CE SEM C SEN O SEM N PRO CD PRO CA PRO CB PRO CG PRO C PRO O PRO N TRP H TRP CA TRP CB TRP CG TRP CD2 TRP CE2 TRP CE3 TRP CD1 TRP NEl TRP HE1 TRP CZ2 TRP CZ3 TRP CR2 TRP C TRP 0 TRP N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CEl TYR CD2 TYR CE2 TYR 161 161 161 161 161 161 162 162 162 162 162 162 162 163 163 163 163 163 163 163 163 163 163 163 163 163 163 163 163 164 164 164 164 164 164 164 164 164 -10.814 -9.109 -10.507 -8.961 -8.831 -9.824 -7.469 -8.584 -11.119 -10.620 -12.299 -10.641 -10.111 -10.624 -8.671 -10.585 -10.329 -10.689 -8.905 -10.745 -8.091 -10.035 -11.121 11. 734 -11.106 -10.610 -11.833 -11.211 -10.807 -11.667 -10.843 -13.049 -9.538 -9.550 -8.747 -11.356 -13.559 -12.713 -13 .333 -14.068 -13.798 -13 .212 -15.225 -15.458 -16.922 -17.645 -18.986 -9.514 640 -8.375 -8.340 -7.199 -5.906 -5.919 -5.754 -5.739 -5.616 -6.002 -5.890 -5.895 -5.586 -5.465 -5.453 -7.236 -6 .410 -8.207 -8.893 -8.321 -8.736 -8.793 -7.631 -7.687 58.146 56. 669 56.217 56. 687 60.125 60.470 61. 018 60.713 62.467 63.027 61.988 63.039 64.096 62 .348 61.509 62.813 62.271 60.808 59.667 58.523 59.503 60.317 58.946 58.372 57.236 58.222 57.106 62.546 63 .069 61.764 61.386 61.471 60 .021 59.634 59 .372 59 .010 59.523 59.160 1.00 18.99 1.00 21.84 1.00 39.69 1.00 28.84 1.00 15.27 1.00 13.98 1.00 15.37 1.00 16.16 1.00 15.23 1.00 15.71 1.00 15.90 1.00 16.06 1.00 15.21 1.00 14.60 1.00 0.00 1.00 10.63 1.00 9.82 1.00 8.73 1.00 4.19 1.00 5.73 1.00 7.68 1.00 7.09 1.00 7.80 1.00 0.00 1.00 3.92 1.00 6.08 1.00 6.60 1.00 10.74 1.00 11.52 1.00 12.03 1.00 0.00 1.00 11.28 1.00 10.37 1.00 8.61 1.00 6.05 1.00 5.19 1.00 8.20 1.00 9.10 -17.583 -10.013 -18.919 -10.074 190 ATOM 1555 CZ TYR 164 -19.609 -8.913 58.904 1.00 6.35 ATOM 1556 OH TYR 164 -20.920 -8.989 58.504 1.00 15.30 ATOM 1557 HH TYR 164 -21.280 -8.115 58.337 1.00 0.00 ATOM 1558 C TYR 164 -15.910 -9.319 62.406 1.00 14.40 ATOM 1559 0 TYR 164 -15.454 -10.456 62.564 1.00 11.39 ATOM 1560 N HIS 165 -17.014 -8.887 63.016 1.00 15.72 ATOM 1561 H HIS 165 -17.347 -7.989 62.813 1.00 0.00 ATOM 1562 CA HIS 165 -17.769 -9.724 63.945 1.00 15.88 ATOM 1563 CB HIS 165 -17.824 -9.061 65.328 1.00 14.50 ATOM 1564 CG HIS 165 -16.476 -8.812 65.939 1.00 13.27 ATOM 1565 CD2 HIS 165 -15.393 -8.142 65.472 1.00 13.68 ATOM 1566 ND1 HIS 165 -16.117 -9.296 67.181 1.00 13.92 ATOM 1567 HDI HIS 165 -16.644 -9.884 67.761 1.00 0.00 *ATOM 1568 CEl HIS 165 -14.872 -8.937 67.448 1.00 9.42 .00 15 ATOM 1569 NE2 HIS 165 -14.413 -8.240 66 .431 1.00 9.18 *0ATOM 1570 HE2 HIS 165 -13.496 -7.895 66.349 1.00 0.00 ATOM 1571 C HIS 165 -19.170 -9.952 63.382 1.00 18.23 ATOM 1572 0 HIS 165 -19.962 -9.017 63.273 1.00 19.85 ATOM 1573 N SER 166 -19.451 -11.201 63.014 1.00 20.28 ATOM 1574 H SER 166 -18.770 -11.903 63.124 1.00 0.00 e..ATOM 1575 CA SER 166 -20.723 -11.619 62.420 1.00 21.65 ATOM 1576 CB SER 166 -20.708 -13.130 62.191 1.00 20.69 ATOM 1577 OG SER 166 -19.443 -13.555 61.714 1.00 32.02 *ATOM 1578 HG SER 166 -19.263 -13.122 60.873 1.00 0.00 25 ATOM 1579 C SER 166 -21.985 -11.260 63 .197 1.00 22.80 ATOM 1580 0 SER 166 -23.005 -10.924 62.597 1.00 23.80 ATOM 1581 N SER 167 -21.944 -11.424 64.515 1.00 24.13 ATOM 1582 H SER 167 -21.139 -11.759 64.954 1.00 0.00 ATOM 1583 CA SER 167 -23.089 -11.117 65.364 1.00 26.47 ATOM 1584 CB SER 167 -23.831 -12.391 65.775 1.00 26.47 ATOM 1585 OG SER 167 -24.476 -12.991 64.664 1.00 33.37 ATOM 1586 HG SER 167 -25.120 -13.631 64.981 1.00 0.00 ATOM 1587 C SER 167 -22.598 -10.401 66.599 1.00 26.39 ATOM 1588 0 SER 167 -22.019 -11.016 67.492 1.00 31.31 ATOM 1589 N LEU 168 -22.788 -9.089 66.616 1.00 25.40 ATOM 1590 H LEU 168 -23.244 -8.656 65.859 1.00 0.00 ATOM 1591 CA LEtJ 168 -22.378 -8.254 67.731 1.00 21.28 ATOM 1592 CB LEU 168 -20.975 -7.692 67.514 1.00 19.91 ATOM 1593 CG LEU 168 -19.787 -8.250 68.290 1.00 19.49 191 ATOM 1594 CD1 LEU 168 ATOM 159 CD1LEU 168 -18.688 -7.208 68.269 1.00 17.54 ATOM 1595 ATOM 1596 ATOM 1597 ATOM 1598 ATOM 1599 ATOM 1600 ATOM 1601 ATOM 1602 1 0 ATOM 1603 ATOM 1604 ATOM 1605 ATOM 1606 ATOM 1607 1 5 ATOM 1608 ATOM 1609 ATOM 1610 ATOM 1611 ATOM 1612 ATOM 1613 ATOM 1614 ATOM 1615 ATOM 1616 ATOM 1617 ATOM 1618 ATOM 1619 ATOM 1620 ATOM 1621 ATOM 1622 ATOM 1623 ATOM 1624 ATOM 1625 ATOM 1626 ATOM 1627 ATOM 1628 ATOM 1629 ATOM 1630 ATOM 1631 CD2 LEU 168 C LEU 168 O LEU 168 N THR 169 H THR 169 CA THR 169 CB TER 169 OGi THR 169 HG1 THR 169 CG2 THR 169 C THR 169 O THR 1.69 N ARG 170 H ARG 170 CA ARG 170 CB ARG 170 CG ARG 170 CD ARG 170 NE ARG 170 HE ARG 170 CZ ARG 170 NH1 ARG 170 HH11 ARG 170 HH12 ARG 170 NH2 ARG 170 HH21 ARG 170 FH22 ARG 170 C ARG 170 o ARG 170 N GLU 171 H GLU 171 CA GLU 171 CB GLU 171 CG GLU 171 CD GLU 171 OE1 GLU 171 0E2 GLU 171 -20.165 -23.338 -23.574 -23.935 -23.739 -24.846 -25.898 -25.244 -25.904 -26.709 -23.962 -22.784 -24.532 -25.461 -23 .819 -24.768 -24.200 -25.258 -24.693 -24.435 -24. 515 -23.989 -23 .732 -23.839 -24.872 -25.304 -24.748 -23.295 -22.162 -24.133 -25.006 -23.764 -24.946 -26.031 -26.910 -27.491 -27.034 -8.547 -7.096 -6.420 897 -7.470 -5.788 -6.091 -6.312 -6.666 -7.327 -4.647 853 -3.453 -3.362 -2.271 -1.075 0.203 1.271 2.587 2.810 3 .512 4.681 4.855 5.384 3 .277 2. 407 3.982 -2.478 113 -3 .044 -3.316 -3.294 -3 .879 873 -2.398 -1.288 -3 .132 69.717 67.799 66.797 68.961 69.729 69.138 70.224 71. 482 72.097 69.854 69.612 69.918 69.683 69.374 70.142 70.111 70.663 70.649 70.897 71. 815 69 .962 70.290 71. 242 69.600 68.705 68.477 68.003 71. 564 71.876 72.425 72.108 73 .815 74.596 74.999 73.838 73 .952 72.826 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 20.20 20.38 23 .06 18.27 0.00 14.78 17.59 16.95 0.00 18.12 14.12 13 .47 13 .49 0.00 12 .83 9 .01 7 .72 7.48 9.76 0.00 9.38 8 0.00 0 .00 6.68 0 .00 0.00 14.22 15.95 16 .49 0.00 18.76 23.85 33.82 38.04 36.00 37.18 ATOM 1632 C GLU 171 -22.584 -4.249 73.900 1.00 17.67 192 ATOM 1633 0 GLU 171 ATOM 1633 0 GL 171 -21.632 -4.009 74.645 1.00 17.85

C.

C

C.

C C C C C C

C

C

C .C

CC..

C

15 ATOM 1634 ATOM 1635 ATOM 1636 ATOM 1637 ATOM 1638 ATOM 1639 ATOM 1640 ATOM 1641 ATOM 1642 ATOM 1643 ATOM 1644 ATOM 1645 ATOM 1646 ATOM 1647 ATOM 1648 ATOM 1649 ATOM 1650 ATOM 1651 ATOM 1652 ATOM 1653 ATOM 1654 ATOM 1655 ATOM 1656 ATOM 1657 ATOM 1658 ATOM 1659 ATOM 1660 ATOM 1661 ATOM 1662 ATOM 1663 ATOM 1664 ATOM 1665 ATOM 1666 ATOM 1667 ATOM 1668 ATOM 1669 ATOM 1670 ATOM 1671

N

H

CA

CB

CG

CD

OE1 0E2

C

0

N

H

GLU 172 GLU 172 GLU 172 GLU 172 GLU 172 GLU 172 GLU 172 GLU 172 GLU 172 GLU 172 ALA 173 ALA 173 ALA 173 ALA 173 ALA 173 ALA 173 GLU 174 GLU 174 GLU 174 GLU 174 GU 174 GLU 174 GLU 174 GLU 174 GLU 174 GLU 174 ARG 175 ARG 175 ARG 175 A.RG 175 ARG 175 ARG 175 ARG 175 ARG 175 ARG 175 ARG 175 ARG 175 ARG 175 -22 .660 -23 .444 -21.606 -22 .061 -23.194 -23 .906 -25.002 -23.390 -20. 315 -19.221 -20.443 -21.328 -19.282 -19.709 -18.551 -17.339 -19.295 -20.266 -18.697 -19.727 -20.082 -20.959 -20.984 -21.622 -18.061 -17.005 -18 .707 -19.572 -18.169 -19.136 -18 .747 -19.658 -21.073 -21. 507 -21.813 -21.276 -20.313 -21.827 -5.331 -5.443 -6.340 -7.542 -8.329 -9.255 -9 .751 -9 .481 -5.764 -6.107 -4.888 -4 .667 -4.250 -3 .376 -3 .415 -3.527 -2 .599 -2 .557 -1.761 -0 .810 0.331 1.383 1 .474 2.132 -2.589 -2.237 -3 .684 -3 .890 -4 .550 -5 .693 -6.564 -7 .776 -7 .405 -7 .272 -7.241 -7.421 -7 .677 -7.290 73.130 72.559 73 .090 72.267 72.899 71. 918 72.253 70.804 72.519 72.970 71. 527 71. 181 70.913 69.747 71.953 72.102 72.694 72.540 73.725 74.322 73.398 74.050 75.297 73.306 74.824 75.345 75.194 74.766 76.232 76.514 77.685 77 .764 77.758 76.885 78.852 80.056 80.134 80.881 1.00 17.32 1.00 0.00 1.00 15.02 1.00 15.64 1.00 19.91 1.00 25.18 1.00 30.20 1.00 27.42 1.00 14.37 1.00 15.38 1.00 12.66 1.00 0.00 1.00 10.27 1.00 9.98 1.00 9.42 1.00 10.18 1.00 11.48 1.00 0.00 1.00 11.44 1.00 10.86 1.00 13.06 1.00 15.17 1.00 14.77 1.00 15.98 1.00 11.55 1.00 15.49 1.00 13.21 1.00 0.00 1.00 15.31 1.00 16.15 1.00 24.24 1.00 31.62 1.00 38.21 1.00 0.00 1.00 43.81 1.00 42.92 1.00 0.00 1.00 0.00

CG

CD

OE1 0E2

C

0

N

H

CA

CE

CG

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NH1 HIH1 1 H{H1 2 193 ATOM 1672 NH2 ARG 175 ATM 67 H2AR 15 -23.087 -6.869 78.741 1.00 45.14 *ee*

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15 ATOM

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25 ATOM

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1673 1674 1675 1676 1677 1678 1679 1680 1681 1682 1683 1684 1685 1686 1687 1688 1689 1690 1691 1692 1693 1694 1695 1696 1697 1698 1699 1700 1701 1702 1703 1704 1705 1706 1707 1708 1709 1710 HH2 1 ARG HH22 ARG C ARG O ARG N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS O LYS N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU o LEU N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CEl TYR CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR 175 175 175 175 176 176 176 176 176 176 176 176 176 176 176 176 176 177 177 177 177 177 177 177 177 177 178 178 178 178 178 178 178 178 178 178 178 178 -23.483 -6.719 -23.645 -6.731 -16.808 -5.102 -15.875 -5.124 -16.691 -5.522 -17.474 -5.464 -15.432 -6.061 -15.643 -6.727 -16.324 -8.074 -16.319 -8.737 -16.972 -10.118 -16.224 -11.112 -16.180 -10.765 -15.257 -11.220 -16.712 -12.029 -14.336 -5.002 -13.164 -5.275 -14.722 -3.799 -15.661 -3.666 -13.776 -2.704 -14.379 -1.617 -14.633 -2.023 -15.280 -0.876 -13.329 -2.429 -13.315 -2.111 -12.157 -1.730 -14.227 -2.014 -15.136 -2.325 -13.900 -1.471 -15.174 -1.068 -15.706 0.301 -14.866 1.413 -15.356 2.681 -17.051 0.493 -17.549 1.756 -16.696 2.846 -17.183 4.110 -18.142 4.016 77.836 79.561 75.808 76. 606 74. 550 73.956 74.031 72.672 72.733 71. 365 71. 402 72.229 73.210 71.853 72.190 73.903 74.164 73.490 73.244 73.325 72.428 70.973 70 .229 70.302 74.654 74.800 75.615 75.444 76.929 77.676 77.313 77.301 77.014 77.023 76.736 76.734 76.465 76.455 1.00 0.00 1.00 0.00 1.00 15.70 1.00 14.24 1.00 15.99 1.00 0.00 1.00 18.88 1.00 20.03 1.00 24.38 1.00 28.28 1.00 32.74 1.00 33.50 1.00 0.00 1.00 0.00 1.00 0.00 1.00 19.37 1.00 20.28 1.00 16.82 1.00 0.00 1.00 15.13 1.00 13.20 1.00 11.03 1.00 8.85 1.00 5.60 1.00 16.41 1.00 16.11 1.00 17.85 1.00 0.00 1.00 19.30 1.00 15.30 1.00 11.87 1.00 9.08 1.00 8.80 1.00 8.22 1.00 8.10 1.00 10.05 1.00 12.49 1.00 0.00 S S S. S @055

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194 ATOM 1711 C TYR 178 -13.135 -2.494 77.752 1.00 22.26 ATOM 1712 O TYR 178 -12.287 -2.148 78.572 1.00 22.67 ATOM 1713 N SER 179 -13.432 -3.764 77.514 1.00 28.96 ATOM 1714 H SER 179 -14.082 -4.002 76.825 1.00 0.00 ATOM 1715 CA SER 179 -12.791 -4.850 78.237 1.00 32.67 ATOM 1716 CB SER 179 -13.775 -6.013 78.416 1.00 34.27 ATOM 1717 OG SER 179 -14.956 -5.590 79.095 1.00 32.95 ATOM 1718 HG SER 179 -15.462 -5.097 78.445 1.00 0.00 ATOM 1719 C SER 179 -11.518 -5.320 77.544 1.00 34.73 ATOM 1720 0 SER 179 -11.467 -6.416 76.994 1.00 37.10 ATOM 1721 N GLY 180 -10.490 -4.483 77.578 1.00 37.24 ATOM 1722 H GLY 180 -10.577 -3.618 78.040 1.00 0.00 ATOM 1723 CA GLY 180 -9.230 -4.834 76.951 1.00 39.63 ATOM 1724 C GLY 180 -8.163 -3.809 77.266 1.00 41.09 1 5 ATOM 1725 O GLY 180 -8.217 -3.151 78.305 1.00 41.30 ATOM 1726 N ALA 181 -7.201 -3.659 76.361 1.00 43.10 ATOM 1727 H ALA 181 -7.216 -4.226 75.564 1.00 0.00 ATOM 1728 CA ALA 181 -6.116 -2.699 76.541 1.00 43.62 ATOM 1729 CB ALA 181 -5.003 -2.975 75.547 1.00 44.37 20 ATOM 1730 C ALA 181 -6.608 -1.261 76.393 1.00 44.60 ATOM 1731 O ALA 181 -5.962 -0.327 76.865 1.00 47.43 ATOM 1732 N GLN 182 -7.749 -1.091 75.731 1.00 42.79 ATOM 1733 H GLN 182 -8.217 -1.875 75.390 1.00 0.00 ATOM 1734 CA GLN 182 -8.339 0.229 75.516 1.00 41.06 25 ATOM 1735 CB GLN 182 -8.819 0.840 76.837 1.00 40.78 ATOM 1736 CG GLN 182 -10.005 0.113 77.453 1.00 42.40 ATOM 1737 CD GLN 182 -10.574 0.836 78.661 1.00 45.06 ATOM 1738 OE1 GLN 182 -10.583 2.069 78.717 1.00 45.31 ATOM 1739 NE2 GLN 182 -11.067 0.075 79.626 1.00 44.73 ATOM 1740 HE21 GLN 182 -11.050 -0.897 79.502 1.00 0.00 ATOM 1741 HE22 GLN 182 -11.427 0.496 80.437 1.00 0.00 ATOM 1742 C GLN 182 -7.405 1.189 74.784 1.00 39.41 ATOM 1743 O GLN 182 -7.449 2.406 74.994 1.00 39.06 ATOM 1744 N THR 183 -6.580 0.625 73.908 1.00 38.44 ATOM 1745 H THR 183 -6.587 -0.340 73.784 1.00 0.00 ATOM 1746 CA THR 183 -5.632 1.390 73.109 1.00 35.60 ATOM 1747 CB THR 183 -4.702 0.455 72.333 1.00 37.11 ATOM 1748 OG1 THR 183 -4.298 -0.628 73.180 1.00 40.31 ATOM 1749 HG1 THR 183 -3.583 -1.085 72.722 1.00 0.00 195 ATOM 1750 CG2 THR 183 ATO 170 G2 HR 83 -3.477 1.212 71.842 1.00 38.58 0 0

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1751 1752 1753 1754 1755 1756 1757 1758 1759 1760 1761 1762 1763 1764 1765 1766 1767 1768 1769 1770 1771 1772 1773 1774 1775 1776 1777 1778 1779 1780 1781 1782 1783 1784 1785 1786 1787 1788 C THR 183 O THR 183 N ASP 184 H ASP 184 CA ASP 184 CB ASP 184 CG ASP 184 ODi ASP 184 0D2 ASP 184 C ASP 184 O ASP 184 N GLY 185 H GLY 185 CA GLY 185 C GLY 185 O GLY 185 N LYS 186 H LYS 186 CA LYS 186 CB LYS 186 CG LYS 186 CD LYS 186 CE LYS 186 NZ LYS 186 HZ1 LYS 186 HZ2 LYS 186 HZ3 LYS 186 C LYS 186 0 LYS 186 N PHE 187 H PHE 187 CA PHE 187 CB PHE 187 CG PHE 187 CD1 PHE 187 CD2 PHE 187 CEl PHE 187 CE2 PHE 187 -6.398 -7.3 65 -5.957 -5.161 -6.616 -5.947 -6.205 -5.410 -7.198 -6.582 -5.569 -7.707 -8.508 -7.784 -8.218 -8.296 -8.438 -8.274 -8.888 -8.986 -8.738 -7.246 -6.949 -5.493 -4.967 -5.150 -5.356 -10.282 11. 107 -10.563 -9.906 -11.849 11. 718 -10.985 -11.684 -9.600 -11. 022 -8.926 2.212 1.725 3 .444 3 .761 4 .312 5 .693 6 .506 7.432 6 .244 3 .679 3 .109 3 .752 4 .173 3 .190 1.737 1.173 1.111l 1.583 -0.282 -0.748 -2.226 -2 .526 -3.956 -4.283 -3 .644 182 -5.264 -0.245 0 .573 139 827 -1.114 -0 .276 -0.991 540 -1.149 -2 .240 -1.853 72.081 71. 485 71.856 72.327 70.889 70.862 72.126 72.391 72.844 69.495 69.089 68.790 69 .171 67.458 67 .404 66.318 68.557 69.398 68.606 70.057 70.287 70.257 70.685 70.606 71.232 69 .632 70.919 67 .980 68.376 67.038 66.789 66.354 65.066 63 .949 62.876 63 .991 61.868 62.978 1.00 32.82 1.00 30.53 1.00 29.67 1.00 0.00 1.00 27.05 1.00 28.47 1.00 30.50 1.00 32.80 1.00 29.45 1.00 24.36 1.00 21.86 1.00 20.06 1.00. 0.00 1.00 16.45 1.00 13.20 1.00 14.03 1.00 13.12 1.00 0.00 1.00 13.63 1.00 17.81 1.00 22.20 1.00 30.53 1.00 34.36 1.00 33 .77 1.00 0.00 1.00 0.00 1.00 0.00 1.00 10.77 1.00 10.89 1.00 9.58 1.00 0.00 1.00 5 .69 1.00 6.05 1.00 6 .66 1.00 5.77 1.00 7.01 1.00 6.32 1.00 6.92 196

S

15 .A

A

A

A

A

20 A

A

A

A

A

A

A

A

A

A

A

A

ATOM 1789 ATOM 1790 ATOM 1791 ATOM 1792 ATOM 1793 ATOM 1794 ATOM 1795 ATOM 1796 ATOM 1797 ATOM 1798 ATOM 1799 ATOM 1800 ATOM 1801 £TOM 1802 TOM 1803 %TOM 1804 TOM 1805 TOM 1806 TOM 1807 TOM 1808 TOM 1809 TOM 1810 TOM 1811 TOM 1812 TOM 1813 TOM 1814 TOM 1815 TOM 1816 TOM 1817 TOM 1818 TOM 1819 CZ PHE C PHE O PHE N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NH1 ARG 187 187 187 188 188 188 188 188 188 188 188 188 189 189 189 189 189 189 189 189 189 190 190 190 190 190 190 190 190 190 190 190 190 190 190 190 190 190 191 -12.368 -11.659 -13.612 -14.139 -14.253 -14.849 -15.937 -17.293 -16.005 -15.328 -15.705 -15.776 -15.415 -16.816 -16.289 -17.305 -17.422 -16.874 -17.892 -17.590 -19.146 -19.341 -20.249 -20.660 -21.012 -21.372 -21.369 -20.510 -22.446 -23.644 -23.756 -24.437 -22.314 -21.402 -23.111 -21.444 -21.683 -22.176 -2.485 -3.482 -2.506 -1.682 -3 .711 -4.529 -3 .971 -3.940 -4.869 -3.269 -2.099 -4.185 -5.099 -3 .887 -3.999 -3.588 078 -4.083 -4.921 097 -4.492 -3 .547 407 -5.307 -3 .879 -3 .771 -2.379 002 603 -2 .069 -3 .016 -1.466 -0.342 0. 008 0.252 057 -3.880 -6 .071 65.962 66.040 65.502 65.510 65.018 66.164 67.079 66.382 68.296 64.044 64.021 63.201 63.217 62.234 60.806 59.747 59.738 58.383 62.468 62.647 62.457 62.290 62.706 64.181 64.610 66.080 66.535 66.808 66.618 66.288 65.981 66.366 66.995 67.211 67.069 61.847 61.565 61.361 1.00 6.09 1.00 6.46 1.00 4.37 1.00 0.00 1.00 4.97 1.00 8.12 1.00 6.99 1.00 4.98 1.00 9.58 1.00 4.81 1.00 7.29 1.00 4.31 1.00 0.00 1.00 6.28 1.00 6.37 1.00 9.47 1.00 13.86 1.00 14.76 1.00 6.49 1.00 7.98 1.00 7.83 1.00 0.00 1.00 8.00 1.00 8.07 1.00 5.07 1.00 9.21 1.00 9.70 1.00 0.00 1.00 7.61 1.00 9.52 1.00 0.00 1.00 0.00 1.00 5.65 1.00 0.00 1.00 0.00 1.00 10.51 1.00 14.83 1.00 10.83 -9.640 -2.397 61.919 1.00 5.13

ATOM

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1820 HHII ARG 1821 HH12 ARG 1822 NH2 ARG 1823 HH21 ARG 1824 HH22 ARG 1825 C ARG 1826 o ARG 1827 N PRO 197

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15 ATOM

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ATOM

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ATOM

ATOM

1828 1829 1830 1831 1832 1833 1834 1835 1836 1837 1838 1839 1840 1841 1842 1843 1844 H 1845 H 1846 1847 H 1848 H CD PRO 191 CA PRO 191 CB PRO 191 CG PRO 191 C PRO 191 O PRO 191 N ARG 192 H ARG 192 CA ARG 192 CB ARG 192 CG ARG 192 CD ARG 192 NE ARG 192 HE ARG 192 CZ ARG 192 NH1 ARG 192 [Hil ARG 192 ~H12 ARG 192 N'H2 ARG 192 H21 ARG 192 H22 ARG 192 C ARG 192 0 ARG 192 N LYS 193 H LYS 193 CA LYS 193 CB LYS 193 CG LYS 193 CD LYS 193 CE LYS 193 NZ LYS 193 HZ1 LYS 193 HZ2 LYS 193 HZ3 LYS 193 C LYS 193 LYS 193 GLU 194 GLU 194 CA GLU 194 -21.942 -23.352 -23.690 -23.267 -24.462 -24. 466 -25.363 -25.336 -26. 454 -26. 689 -25.592 -25.878 -27.001 -26. 904 -28.172 -28.390 -27.658 -29.261 -29.121 -28.968 -29.999 -27.708 -27.713 -28.765 -28.664 -30. 052 -31. 054 -32.442 -33.390 -34.851 -35.100 -34.800 -34.562 -3 6.117 -30.595 -31.078 -30.505 -30.052 -31.010 -7 .523 -5 .787 -7 .156 -8 .095 -5.298 -5 .630 -4.469 -4.180 -3 .983 -2.491 -1.606 -0.148 0.383 0 .465 0.743 0. 628 0.282 0 .900 1.243 1.357 1.507 -4.761 -5 .581 -4.497 -3 .846 -5.154 -4 .605 -5.207 -4.538 -4.902 -6 .373 -6.768 -6.822 -6.545 -5 .004 -5.970 -3 .803 -3 .073 -3.580 61. 465 60.540 59.946 61. 017 61. 471 62.659 60.963 60. 025 61. 787 61. 575 62.105 61.810 62.583 63 .553 62 .064 60.764 60.181 60. 355 62.841 63 .822 62.438 61.449 60.530 62.207 62.939 62 .021 63 .040 62.954 63 .950 63 .677 63 .679 64.593 62.914 63 .544 60.595 60.009 60.027 60.494 58.672 1.00 10.41 1.00 10.84 1.00 9.30 1.00 9.83 1.00 12.64 1.00 15.28 1.00 12.45 1.00 0.00 1.00 12.10 1.00 9.12 1.00 2.40 1.00 7.40 1.00 8.66 1.00 0.00 1.00 8.48 1.00 11.77 1.00 0.00 1.00 0.00 1.00 11.80 1.00 0.00 1.00 0.00 1.00 16.67 1.00 16.54 1.00 24.12 1.010 0.00 1.00 27.69 1.00 30.58 1.00 36.83 1.00 42.21 1.00 43.76 1.00 45.07 1.00 0.00 1.00 0.00 1.00 0.00 1.00 29.29 1.00 30.78 1.00 30.08 1.00 0.00 1.00 29.65 1849 1850 1851 1852 1853 1854 1855 1856 1857 1858 1859 1860 1861 1862 1863 1864 1865 1866 198 ATOM 1867 CB GLU 194 ATOM 867 B GL 194 -31.443 -2.124 58.468 1.00 31.51

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15 ATOM

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20 ATOM

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25 ATOM

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1868 1869 1870 1871 1872 1873 1874 1875 1876 1877 1878 1879 1880 1881 1882 1883 1884 1885 1886 1887 1888 1889 1890 1891 1892 1893 1894 1895 1896 1897 1898 1899 1900 1901 1902 1903 1904 1905 CG GLU 194 CD GLU 194 OE1 GLU 194 0E2 GLU 194 C GLU 194 O GLU 194 N GLN 195 H GLN 195 CA GLN 195 CB GLN 195 CG GLN 195 CD GLN 195 OE1 GLN 195 NE2 GLN 195 HE21 GLN1 195 H{E22 GLN 195 C GLN 195 o GLN 195 N GLY 196 H GLY 196 CA GLY 196 C GLY 196 O GLY 196 N THR 197 H THR 19 CA THR 197 CB THR 197 OGi TER 197 HG1 THR 197 CG2 THR 197 C THR 197 O TER 197 N TYR 198 H TYR 198 CA TYR 198 CB TYR 198 CG TYR 198 CD1 TYR 198 -32.478 -31.843 -32.144 -31. 040 -29.996 -28. 815 -30. 475 -31. 430 -29.638 -30. 495 -31. 179 -30.242 -29.244 -30.550 -31.346 -29.951 -28.949 -29.574 -27.661 -27.192 -26.934 -26.347 -25.769 -26.517 -27.003 -25.966 -27.056 -27.907 -28.275 -27.883 -25.050 -25.333 -23.933 -23.787 -22.936 -21.686 -21.941 -22 .509 -1 .620 -1 .000 -1 .447 -0 .057 -3 .978 -3 .656 -4 .676 -4 .874 -5 .143 -5 .896 -7.137 -8 .321 -8.286 -9.375 -9.348 -10 .143 -3 .987 -2-.973 -4 .142 -4 .960 -3 096 -2 .009 -1.050 -2.130 -2 .893 -1.160 -0.415 -1.361 -1.934 0 .478 -1.897 -3.033 -1.259 -0.345 -1.814 -2.239 -3 .345 -3 .072 59.468 60.701 61. 828 60.545 57.608 57.708 56. 585 56. 579 55.486 54.468 55.007 55.098 55.816 54.356 53.792 54.423 54.779 54.488 54.502 54.770 53 .811 54.687 54.169 56.003 56.375 56.944 57.740 58.392 57.715 56.826 57.912 58.312 58.244 57 .907 59.148 58.363 57.363 56.118 1.00 34.14 1.00 39.15 1.00 43.02 1.00 42.87 1.00 29.35 1.00 30.02 1.00 27.79 1.00 0.00 1.00 26.98 1.00 32.16 1.00 38.27 1.00 42.30 1.00 46.88 1.00 43.75 1.00 0.00 1.00 0.00 1.00 23.15 1.00 24.44 1.00 20.21 1.00 0.00 1.00 17.86 1.00 17.20 1.00 15.58 1.00 16.43 1.00 0.00 1.00 12.41 1.00 12.16 1.00 12.64 1.00 0.00 1.00 7.90 1.00 12.59 1.00 13.67 1.00 8.91 1.00 0.00 1.00 8.91 1.00 6.61 1.00 9.50 1.00 6.46 199 ATOM 1906 CE1 TYR 198 ATM196C~ YR18 -22.777 -4.092 55.212 1.-00 9.83

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1 5 ATOM

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20 ATOM

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1907 1908 1909 1910 1911 1912 1913 1914 1915 1916 1917 1918 1919 1920 1921 1922 1923 1924 1925 1926 1927 1928 1929 1930 1931 1932 1933 1934 1935 1936 1937 1938 1939 1940 1941 1942 1943 1944 CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR C TYR 0 TYR N ALA H ALA CA ALA CB ALA C ALA 0 ALA N LEU F LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N SER H SER CA SER CB SER OG SER HG SER C SER O SER N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU 198 198 198 198 198 198 198 199 199 199 199 199 199 200 200 200 200 200 200 200 200 200 201 201 201 201 201 201 201 201 202 202 202 202 202 202 202 202 -21.643 -21. 905 -22.469 -22.692 -23 .165 -22.560 -23.001 -21. 748 -21. 423 -21 .306 -22.149 -19 .851 -19.422 -19.084 -19.476 -17.674 -16.893 -15.369 -14.783 -14 .793 -17.571 -17. 970 -17.087 -16 .753 -16.961 -17 .707 -19.077 -19.090 -15 .491 -14.765 -15 .051 -15.662 -13 .657 -12.835 -12.959 -11 .634 -13 .371 -13 .534 -4.671 -5.693 -5.403 -6.430 -6.078 -0.696 0.436 -1.001 -1.916 0.025 0.012 -0.214 -1.361 0.869 1.742 0.821 1.746 1.757 0.386 2.844 1.313 2.433 0.463 -0.412 0.824 -0.196 -0.311 -0.707 0.869 -0.104 1.984 2.736 2.124 2.838 4.352 5.027 4.665 2.893 57. 675 56.778 55.549 54. 649 53.883 60. 091 59.912 61. 091 61. 229 62.017 63.283 62.348 62 .501 62.380 62.171 62.715 61. 784 61.924 61. 569 61. 012 64.158 64.461 65.057 64.768 66.466 67.339 66.977 66.093 66.862 66.653 67.439 67.609 67 .853 66.771 66.596 66.905 65.176 69.156 1.00 9.33 1.00 12.76 1.00 13.23 1.00 15.25 1.00 0.00 1.00 8.51 1.00 11.67 .L.00 8.59 1.00 0.00 1.00 6.98 1.00 7.55 1.00 8.45 1.00 9.19 1.00 7.78 1.00 0.00 1j.00 7.79 1.00 9.17 1.00 15.15 1.00 12.28 1.00 13.36 1.00 9.38 1.00 13.05 1.00 10.24 1.00 0.00 1 .00 8.31 1.00 6.89 1.00 7.26 1.00 0.00 1.00 9.36 1.00 9.48 1.00 10.31 1.00 0.00 1.00 11.15 1.00 11.80 1.00 12.43 1.00 15.63 1.00 18.37 1.00 14.24 .200 ATOM 1945 0 LEU 202 ATM 94 0 LE 22 -14.446 3.617 69.546 1.00 12.46

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15 ATOM

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1946 N ILE 1947 H ILE 1948 CA ILE 1949 CB ILE 1950 CG2 ILE 1951 CG1 ILE 1952 CD ILE 1953 c ILE 1954 o ILE 1955 N TYR 1956 H TYR 1957 CA TYR 1958 CB TYR 1959 CG TYR 1960 CD1 TYR 1961 CEl TYR 1962 CD2 TYR 1963 CE2 TYR 1964 CZ TYR 1965 OH TYR 1966 HH TYR 1967 C TYR 1968 0 TYR 1969 N GLY 1970 H GLY 1971 CA GL'Y- 1972 C GLY 1973 o GLY 1974 N LYS 1975 H LYS 1976 CA LYS 1977 CB LYS 1978 CG LYS 1979 CD LYS 1980 CE LYS 1981 NZ LYS 1982 HZ1 LYS 203 203 203 203 203 203 203 203 203 204 204 204 204 204 204 204 204 204 204 204 204 204 204 205 205 205 205 205 206 206 206 206 206 206 206 206 206 206 -12.399 -11.707 -12.162 -11.490 -11.866 -11.887 -10.981 -11.195 -10.265 -11.419 -12.205 -10.544 -10.831 864 -8.493 590 2.736 69.825 1.00 17.13 2.154 69.453 1.00 0.00 3.433 71.081 1.00 18.71 2.540 72.137 1.00 19.35 3.011 73.529 1.00 21.06 1.084 71.957 1.00 23.07 0.139 72.713 1.00 26.33 4.580 70.853 1.00 19.13 4.481 70.046 1.00 20.24 5.667 71.571 1.00 19.51 5.723 72.147 1.00 0.00 6.818 71.520 1.00 20.06 7.714 70.324 1.00 21.97 8.866 70.276 1.00 23.47 8.637 70.173 1.00 24.19 9.685 70.211 1.00 26.94 -10.307 10.177 70.411 1.00 24.45 -9.410 11.232 70.449 1.00 26.76 -8.056 10.977 70.354 1.00 28.21 -7.160 12.014 70.424 1.00 37.45 -7.642 12.839 70.522 1.00 0.00 -10.724 7.594 72.814 1.00 20.33 -11.827 8.055 73.125 1.00 18.87 -9.643 7.695 73.584 1.00 21.84 -8.815 7.295 73.279 1.00 0.00 -9.684 8.394 74.858 1.00 20.17 -10.621 7.710 75.837 1.00 19.37 -11.482 8.360 76.424 1.00 21.75 -10.494 6.390 75.963 1.00 18.95 -9.814 5.924 75.440 1.00 0.00 -11.330 5.597 76.866 1.00 21.57 -11.065 5.982 78.323 1.00 23.25 -9.920 5.239 78.982 1.00 27.37 -9.687 5.772 80.394 1.00 33 -9.061 4.730 81.315 1.00 35.90 -10.000 3.606 81.620 1.00 37.25 -10.264 3 .129 80.733 1.00 0.00 -10.854 3.986 82.078 1.00 0.00 ATOM 1983 HZ2 LYS 201 ATOM 1984 HZ3 LYS 206 -9.536 2.926 82.259 1.00 0.00 ATOM 1985 C LYS 206 -12.829 5.688 76.577 1.00 21.03 ATOM 1986 0 LYS 206 -13.649 5.298 77.403 1.00 22.71 ATOM 1987 N THR 207 -13.185 6.174 75.396 1.00 20.66 ATOM 1988 H THR 207 -12.532 6.456 74.735 1.00 0.00 ATOM 1989 CA TER 207 -14.582 6.297 75.020 1.00 20.40 ATOM 1990 CB THR 207 -14.992 7.782 74.907 1.00 23.55 ATOM 1991 OGi THR 207 -14.482 8.507 76.033 1.00 25.33 ATOM 1992 HG1 THR 207 -13.533 8.667 75.914 1.00 0.00 ATOM 1993 CG2 THR 207 -16.507 7.919 74.890 1.00 24.82 ATOM 1994 C THR 207 -14.777 5.589 73.679 1.00 19.07 ATOM 1995 0 THR 207 -13.893 5.630 72.824 1.00 20.35 *ATOM 1996 N VAL 208 -15.906 4.900 73.531 1.00 16.81 *.ATOM 1997 H VAL 208 -16.535 4.881 74.280 1.00 0.00 1 5 ATOM 1998 CA VAL 208 -16.240 4.156 72.317 1.00 15.40 *ATOM 1999 CB VAL 208 -16.952 2.803 72.665 1.00 12.63 :::ATOM 2000 CG1 VAL 208 -17.532 2.159 71.422 1.00 16.18 ATOM 2001 CG2 VAL 208 -15.972 1.841 73.316 1.00 8.54 *ATOM 2002 C VAL 208 -17.115 4.965 71.355 1.00 15.91 ATOM 2003 0 VAL 208 -18.159 5.483 71.748 1.00 16.07 ATOM 2004 N TYR 209 -16.668 5.061 70.100 1.00 17.15 ATOM 2005 H TYR 209 -15.820 4.658 69.884 1.00 0.00 *ATOM 2006 CA TYR 209 -17.366 5.775 69.026 1.00 13.45 ATOM 2007 CB TYR 209 -16.393 6.701 68.298 1.00 12.87 ATOM 2008 CG TYR 209 -15.821 7.795 69.153 1.00 12.70 ATOM 2009 CD1 TYR 209 -16.246 9.107 69.005 1.00 14.59 ATOM 2010 CEl TYR. 209 -15.721 10.124 69.786 1.00 17.80 ATOM 2011 CD2 TYR 209 -14.851 7.523 70.108 1.00 12.27 ATOM 2012 CE2 TYR 209 -14.322 8.531 70.896 1.00 15.57 ATOM 2013 CZ TYR 209 -14.760 9.830 70.732 1.00 16.21 ATOM 2014 OH TYR 209 -14.250 10.837 71.519 1.00 16.78 ATOM 2015 HH TYR 209 -14.677 11.671 71.296 1.00 0.00 ATOM 2016 c TYR 209 -17.956 4.790 68.014 1.00 11.19 ATOM 2017 0 TYR 209 -17.350 3.770 67.706 1.00 12.29 ATOM 2018 N HIS 210 -19.143 5.096 67.505 1.00 10.27 ATOM 2019 H HIS 210 -19.587 5.914 67.804 1.00 0.00 ATOM 2020 CA HIS 210 -19.811 4.244 66.525 1.00 9.28 ATOM 2021 CB HIS 210 -21.123 3.697 67.085 1.00 11.42 ATOM 2022 CG HIS 210 -20.981 2.980 68.390 1.00 13.02 202

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2023 CD2 HIS 2024 ND1 HIS 2025 HD1 HIS 2026 CEl HIS 2027 NE2 HIS 2028 HE2 HIS 2029 c HIS 2030 o HIS 2031 N TYR 2032 H TYR 2033 CA TYR 2034 CB TYR 2035 CG TYR 2036 CD1 TYR 2037 CEl TYR 2038 CD2 TYR 2039 CE2 TYR 2040 CZ TYR 2041 OH TYR 2042 HH TYR 2043 C TYR 2044 0 TYR 2045 N LEU 2046 H LEU 2047 CA LEU 2048 CB LEU 2049 CG LEU 2050 CD1 LEU 2051 CD2 LEU 2052 C LEU 2053 0 LEU 2054 N ILE 2055 H ILE 2056 CA ILE 2057 CB ILE 2058 CG2 ILE 2059 CG1 ILE 2060 CD ILE 2061 C ILE 210 210 210 210 210 210 210 210 211 211 211 211 211 211 211 211 211 211 211 211 211 211 212 212 212 212 212 212 212 212 212 213 213 213 213 213 213 213 213 -21.058 -20.751 -20. 594 -20.696 -20.878 -20.870 -20.143 -20. 690 -19.839 -19. 408 -20. 115 -18.810 -17. 960 -17.064 -16.270 -18.043 -17.254 -16. 371 -15.579 -15.854 -20.958 -20.728 -21.949 -22.062 -22 .852 -24.174 -25.494 -25.835 -25.475 -22.226 -21. 636 -22.275 -22.665 -21.757 -20.691 -20.328 -19 .446 -18.405 -22.972 3.429 69.663 1.00 12.81 1.624 68.474 1.00 12.75 1.000 67.722 1.00 0.00 1.268 69.744 1.00 13.87 2.345 70.485 1.00 13.61 2.365 71.458 1.00 0.00 5.074 65.301 1.00 9.07 6.165 65.430 1.00 11.99 4.550 64.119 1.00 9.30 3.671 64.065 1.00 0.00 5.239 62.860 1.00 8.50 5.602 62.136 1.00 7.82 6.618 62.866 1.00 9.31 6.224 63.862 1.00 10.88 7.154 64.531 1.00 9.13 7.973 62.559 1.00 10.28 8.911 63.223 1.00 9.76 8.492 64.205 1.00 9.78 9.405 64.857 1.00 11.29 10.307 64.614 1.00 0.00 4.331 61.981 1.00 6.82 3.124 61.917 1.00 8.26 4.917 61.324 1.00 6.71 5.893 61.376 1.00 0.00 4.185 60.451 1.00 5.46 4.959 60.360 1.00 7.18 4.395 59.818 1.00 9.03 5.015 58.480 1.00 12.52 2.889 59.756 1.00 11.67 4.035 59.065 1.00 6.62 4.975 58.535 1.00 5.44 2.827 58.521 1.00 7.03 2.078 59.020 1.00 0.00 2.583 57.187 1.00 6.11 1.477 57.174 1.00 8.10 1.111 55.733 1.00 8.26 1.940 57.935 1.00 7.79 0.858 58.106 1.00 4.59 2.142 56.384 1.00 7.52 203 ATOM 2062 o ILE 213 -23.708 1.254 56.806 1.00 7.66

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15 ATOM

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2063 2064 2065 2066 2067 2068 2069 2070 2071 2072 2073 2074 2075 2076 2077 2078 2079 2080 2081 2082 2083 2084 2085 2086 2087 2088 2089 2090 2091 2092 2093 2094 2095 2096 2097 2098 2099

N

H

CA

CB

OG

HG

C

0

N

H

CA

CB

CG

CD

OE1 NE2 HE21 HE22

C

O

N

H

CA

CB

CG

OD1 OD2

C

O

N

H

CA

CB

CG

CD

CE

NZ

SER 214 SER 214 SER 214 SER 214 SER 214 SER 214 SER 214 SER 214 GLN 215 GLN 215 GLN 215 GLN 215 GLN 215 GLN 215 GLN 215 GLN 215 GLN 215 GLN 215 GLN 215 GLN 215 ASP 216 ASP 216 ASP 216 ASP 216 ASP 216 ASP 216 ASP 216 ASP 216 ASP 216 LYS 217 LYS 217 LYS 217 LYS 217 LYS 217 LYS 217 LYS 217 LYS 217 -23.212 2.781 -22.616 3.483 -24.365 2.429 -25.403 3.550 -26.664 3.122 -27.246 2.924 -23.944 2.183 -22.868 2.608 -24.773 1.454 -25.622 1.144 -24.501 1.145 -24.656 -0.356 -24.198 -0.815 -24.267 -2.320 -24.990 -3.002 -23.500 -2.848 -22.916 -2.272 -23.571 -3.817 -25.496 1.919 -26.702 1.807 -24.997 2.742 -24.024 2.829 -25.878 3.523 -25.195 4.820 -23.933 4.580 -23.826 3.556 -23.041 5.451 -26.447 2.743 -26.222 1.539 -27.143 3.454 -27.270 4.407 -27.762 2.863 -28.498 3.946 -27.606 4.818 -26.611 5.688 -27.307 6.796 -26.330 7.760 -25.793 8.221 55.250 54.920 54.442 54.517 54.045 54.794 53.000 52.574 52.266 52.659 50.870 50.632 49.265 49.102 49.825 48.160 47.626 48.059 50.014 50.218 49.096 49.029 48.239 47.769 46.941 46.232 46.986 47.055 46.923 46.173 46.343 44.986 44.189 43.290 44.067 44.850 45.446 44.683 1.00 8.29 1.00 0.00 1.00 11.71 1.00 13.40 1.00 21.53 1.00 0.00 1.00 13.39 1.00 14.33 1.00 16.85 1.00 0.00 1.00 21.53 1.00 21.76 1.00 25.99 1.00 27.71 1.00 31.50 1.00 26.57 1.00 0.00 1.00 0.00 1.00 23.57 1.00 26.27 1.00 24.50 1.00 0.00 1.00 25.05 1.00 24.39 1.00 24.49 1.00 24.62 1.00 22.90 1.00 26.80 1.00 27.31 1.00 30.69 1.00 0.00 1.00 32.79 1.00 36.64 1.00 41.04 1.00 45.48 1.00 49.13 1.00 51.31 1.00 0.00 ATOM 2100 HZ1 LYS 217 -204 ATOM 2101 HZ2 LYS 217 -25.684 7.252 46.083 1.00 0.00 0 *0 0 0**0 0

U

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20 ATOM

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2102 2103 2104 2105 2106 2107 2108 2109 2110 2111 2112 2113 2114 2115 2116 2117 2118 2119 2120 2121 2122 2123 2124 2125 2126 2127 2128 2129 2130 2131 2132 2133 2134 2135 2136 2137 2138 2139

LYS

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LYS

LYS

HZ3 LYS 217 217 217 218 218 218 218 218 218 219 219 219 219 219 220 220 220 220 220 220 220 220 220 220 220 220 220 221 221 221 221 221 221 221 221 221 221 221 -26.846 -26.758 -27.058 -25.567 -25.384 -24.517 -23.534 -23.781 -22.812 -24.222 -25.007 -23.588 -22.322 -21.617 -22.043 -22.639 -20.857 -20.334 -19.724 -19.446 -18.686 -17.267 -17.249 -16.790 -16.781 -21.119 -22.221 -20.112 -19.285 -20.194 -19.445 -19.910 -19.410 -19.782 -20.805 -21.185 -20.665 -20.995 8.482 2.156 1.116 2.731 3.544 2.175 3.265 1.011 0.490 0.624 1.034 -0.472 -0.078 -0.937 1.218 1.850 1.699 2.951 2.658 3.937 3.669 3.293 2.479 4.091 3.043 1.954 2.346 1.677 1.336 1.863 0.759 -0.632 -1.318 -2.629 -1.289 -2.605 -3.267 -4.579 45.988 44.077 43.497 43.959 44.464 43.113 42.728 43.773 43.217 44.968 45.378 45.674 46.411 46.943 46.472 46.038 47.157 46.464 45.103 44.349 43.057 43.318 43.959 43.777 42.432 48.636 49.019 49.459 49.059 50.903 51.641 51.334 50.231 49.974 52.174 51.928 50.826 50.584 1.00 0.00 1.00 31.55 1.00 33.38 1.00 30.81 1.00 0.00 1.00 28.71 1.00 27.61 1.00 29.11 1.00 31.99 1.00 26.78 1.00 0.00 1.00 22.67 1.00 22.34 1.00 22.37 1.00 18.20 1.00 0.00 1.00 15.98 1.00 19.42 1.00 24.14 1.00 30.32 1.00 35.44 1.00 39.63 1.00 0.00 1.00 0.00 1.00 0.00 1.00 13.83 1.00 12.56 1.00 10.21 1.00 0.00 1.00 9.57 1.00 8.91 1.00 9.85 1.00 9.27 1.00 13.17 1.00 10.94 1.00 13.53 1.00 12.86 1.00 19.40 CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS O LYS N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CE1 TYR CD2 TYR CE2 TYR CZ TYR OH TYR 205 ATOM 2140 HH TYR 221 ATM 240R YR21 -20.857 -4.758 49.645 1.ZO 0.00 4 *4*e 4* 4 4* 4. 4 4

S

9 ATOM 2141 ATOM 2142 ATOM 2143 ATOM 2144 ATOM 2145 ATOM 2146 ATOM 2147 ATOM 2148 1 0 ATOM 2149 ATOM 2150 ATOM 2151 ATOM 2152 ATOM 2153 1 5 ATOM 2154 ATOM 2155 ATOM 2156 ATOM 2157 ATOM 2158 20 ATOM 2159 ATOM 2160 ATOM 2161 ATOM 2162 ATOM 2163 25 ATOM 2164 ATOM 2165 ATOM 2166 ATOM 2167 ATOM 2168 ATOM 2169 ATOM 2170 ATOM 2171 ATOM 2172 ATOM 2173 ATOM 2174 ATOM 2175 ATOM 2176 ATOM 2177

C

0

N

H

CA

CB

SG

C

0

N

H

CA

CB

CG2 CG1

CD

C

0

N

CD

CA

CB

TYR 221 TYR 221 CYS 222 CYS 222 CYS 222 CYS 222 CYS 222 CYS 222 CYS 222 ILE 223 ILE 223 ILE 223 ILE 223 ILE 223 ILE 223 ILE 223 ILE 223 ILE 223 PRO 224 PRO 224 PRO 224 PRO 224 PRO 224 PRO 224 PRO 224 GLU 225 GLU 225 GLU 225 GLU 225 GLU 225 GLU 225 GLTJ 225 GLU 225 GLU 225 GU 225 GLY 226 GLY 226 -19.574 3.174 -18.616 3.651 -20.090 3.724 -20.863 3.315 -19.570 4.964 -19.774 6.126 -21.492 6.676 -20.244 5.331 -21.345 4.860 -19.521 6.097 -18.601 6.331 -20.059 6.638 -18.925 6.995 -19.475 7.742 -18.225 5.712 -16.938 5.946 -20.697 7.902 -20.109 8.528 -21.936 8.234 -22.736 7.595 -22.621 9.422 -23.707 9.672 -24.088 8.271 -21.715 10.647 -21.090 11.126 -21.645 11.124 -22.179 10.664 -20.830 12.280 -21.055 13.465 -22.439 14.080 -22.526 15.306 -22.863 15.151 -22-228 16.418 -19.330 12.006 -18.536 12.937 -18.939 10.740 -19.593 10.021 -17.532 10.407 51. 330 50.714 52.422 52.870 52.967 51.986 51. 784 54.270 54.579 55.074 54.815 56.306 57.300 58.498 57.762 58.525 55.706 54.823 56.102 57.167 55.572 56 .616 57.014 55.374 56.315 54.132 53 .448 53.738 54.680 54.631 55.516 56.712 55.020 53 .641 53.502 53.707 53.791 53 .626 1.00 10.79 1.00 10.37 1.00 9.88 1.00 0.00 1.00 9.81 1. V0 10.60 1.00 17.23 1. 00 9.69 1.CO 7.62 1.00 10.22 1.00 0.00 1 .00I 9.93 1.00 6.84 1.00^ 5.29 1.00O 6.96 1.00 9.34 1.00 11.78 1.00 12.45 1.00 13.13 1.00 13.77 1.00 12.77 1.00 12.95 1.00 13.82 1.20 11.50 1.00 9.13 1.00 14.71 1 .0r0 0.00 1.00 15.88 1.00 20.79 1.00 26.35 1.00 32.15 1.00 33.44 1.00 34.61 1.00 13.50 1.00 14.62 1.00 10.60 1.00 0.00 1.00 9.49

CG

CD

QEl 0E2

C

0

N

H-

ATOM 2178 CA GLY 226 -206 ATOM 2179 C GLY 226 a

S

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2180 0 GLY 2181 N THR 2182 H THR 2183 CA THR 2184 CB THR 2185 OGi THR 2186 HG1 THR 2187 CG2 THR 2188 C THR 2189 0 THR 2190 N LYS 2191 H LYS 2192 CA LYS 2193 CB LYS 2194 CG LYS 2195 CD LYS 2196 CE LYS 2197 NZ LYS 2198 HZi LYS 2199 HZ2 LYS 2200 HZ3 LYS 2201 c LYS 2202 o LYS 2203 N PHE 2204 H PHE 2205 CA PHE 2206 CB PHE 2207 CG PHE 2208 CD1 PHE 2209 CD2 PHE 2210 CEl PHE 2211 CE2 PHE 2212 CZ PHE 2213 c PHE 2214 0 PHE 2215 N ASP 2216 H ASP 2217 CA ASP 226 227 227 227 227 227 227 227 227 227 228 228 228 228 228 228 228 228 228 228 228 228 228 229 229 229 229 229 229 229 229 229 229 229 229 230 230 230 -13.191 -13.305 -13.350 -16.191 -16.643 -16.343 -15.978 -17.056 -18.118 -19.153 -20. 385 -21.505 -21. 135 -20.889 -20.321 -21. 945 -16.114 -15.136 -16 .412 -17 .223 -15.590 -14.963 -14.272 -14.983 -12.913 -14.350 -12.280 -13 .003 -16 .403 -17.617 -15.728 -14 .760 -16.394 9.664 51.370 1.00 11.75 10.261 50.623 1.00 0.00 7.891 49.783 1.00 9.00 7.513 50.609 1.00 11.40 6.835 51.530 1.00 13.43 7.187 49.330 1.00 11.00 7.748 48.614 1.00 0.00 5.986 48.927 1.00 11.19 6.329 47.882 1.00 15.00 7.293 48.448 1.00 11.92 7.410 47.598 1.00 15.46 8.048 48.399 1.00 16.88 9.394 48.914 1.00 26.16 10.007 48.111 1.00 0.00 9.311 49.557 1.00 0.00 9.804 49.428 1.00 0.00 4.890 48.452 1.00 10.75 5.153 47.745 1.00 8.11 3.661 48.866 1.00 8.50 3.514 49.399 1.00 0.00 2.504 48.552 1.00 5.46 1.973 49.843 1.00 4.60 3.031 50.669 1.00 4.48 3.792 51.590 1.00 7.15 3.269 50.525 1.00 5.66 4.767 52.352 1.00 4.56 4.242 51.284 1.00 5.66 4.991 52.199 1.00 2.65 1.398 47.891 1.00 8.16 1.312 48.086 1.00 5.71 0.538 47.126 1.00 9.14 0.670 47.008 1.00 0.00 -0.574 46.445 1.00 9.38 -17.172 9.830 52.273 1.00 7.50 -18.004 9.771 51.373 1.00 7.18 -15.926 9.395 52.140 1.00 11.32 -15.314 9.439 52.909 1.00 0.00 -15.419 8.798 50.907 1.00 11.27 -13.911 8.469 51.054 1.00 10.87 207 0O S. S

@OSS

*5S* 0e 5 6 *6 S S 5555 *5

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2218 CB ASP 2219 CG ASP 2220 ODI ASP 2221 OD2 ASP 2222 C ASP 2223 0 ASP 2224 N THR 2225 H THR 2226 CA THR 2227 CB THR 2228 OGI THR 2229 HG1 THR 2230 CG2 THR 2231 C THR 2232 0 THR 2233 N LEU 2234 H LEU 2235 CA LEU 2236 CB LEU 2237 CG LEU 2238 CD1 LEU 2239 CD2 LEU 2240 C LEU 2241 o LEU 2242 N TRP 2243 H TRP 2244 CA TRP 2245 CB TRP 2246 CG TRP 2247 CD2 TRP 2248 CE2 TRP 2249 CE3 TRP 2250 CD1 TRP 2251 NEI TRP 2252 HE1 TRP 2253 CZ2 TRP 2254 CZ3 TRP 2255 CH2 TRP 2256 C TRP 230 230 230 230 230 230 231 231 231 231 231 231 231 231 231 232 232 232 232 232 232 232 232 232 233 233 233 233 233 233 233 233 233 233 233 233 233 233 233 -15.574 -1.052 -15.869 -0.274 -15.274 -0.608 -16.698 0.654 -16.651 -1.761 -17.541 -2.573 -15.824 -1.904 -15.090 -1.275 -15.971 -3.007 -14.953 -4.131 -13.627 -3.614 -13.496 -3.068 -15.127 -4.692 -15.700 -2.501 -15.050 -1.477 -16.211 -3.224 -16.795 -3.989 -16.001 -2.885 -16.881 -3.761 -18.367 -3.450 -19.044 -4.612 -18.576 -2.150 -14.534 -3.090 -14.021 -2.433 -13.873 -4.022 -14.348 -4.510 -12.464 -4.305 -11.979 -5.466 -10.687 -6.058 -9.359 -5.570 -8.458 -6.423 -8.844 -4.493 -10.536 -7.154 -9.204 -7.380 -8.861 -8.107 -7.073 -6.237 -7.458 -4.308 -6.592 -5.177 -11.617 -3.062 45.246 43.981 42.947 43.998 47.363 47.108 48.391 48.547 49.321 49.036 49.171 48.382 47.635 50.719 50.898 51.704 51.481 53.099 53.994 54.121 54.828 54.897 53.473 54.374 52.796 52.099 53.057 52.188 52.650 52.381 53.060 51.641 53.440 53.693 54.265 53.021 51.601 52.292 52.772 1.00 8.63 1.00 8.43 1.00 9.85 1.00 11.91 1.00 10.64 1.00 11.10 1.00 10.48 1.00 0.00 1.00 6.74 1.00 7.00 1.00 8.09 1.00 0.00 1.00 9.33 1.00 5.98 1.00 4.61 1.00 7.05 1.00 0.00 1.00 8.76 1.00 6.96 1.00 6.67 1.00 7.35 1.00 6.04 1.00 7.18 1.00 9.95 1.00 6.47 1.00 0.00 1.00 6.87 1.00 3.74 1.00 4.57 1.00 8.34 1.00 6.83 1.00 8.52 1.00 5.21 1.00 6.92 1.00 0.00 1.00 8.01 1.00 6.16 1.00 7.69 1.00 7.29 a S S. S S 5.5.

208 9* 9.

9 9

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

9* *9999.

2270 2271 2272 2273 2274 2275 2276 2277 2278 2279 2280 2281 2282 2283 2284 2285 2286 2287 2288 2289 2290 2291 2292 2293 2294 2295 2257 0 TRP 2258 N GLN 2259 H GLN 2260 CA GLN 2261 CB GLN 2262 CG GLN 2263 CD GLN 2264 0E1 GLN 2265 NE2 GLN 2266 HE21 GLN 2267 HE22 GLN 2268 C GLN 2269 0 GLN N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEtJ C LEU 0 LEU N VAL H VAL CA VAL CB VAL CG1 VAL CG2 VAL C VAL O VAL N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU 233 234 234 234 234 234 234 234 234 234 234 234 234 235 235 2 35 235 235 235 235 235 235 236 236 236 -36 36 326 3 6 236 237 237 237 237 237 237 237 237 237 -12 .613 -11. 169 -11.443 -10.836 -11.380 -12 .586 -10.487 -9.531 -10.789 -11.449 -10.554 -12.689 -13 .364 -13 .081 -14.566 -15.185 -16.630 -15.109 -12.216 -11.579 -12.158 -12.661 -11.383 -11.604 -10.658 -13 .042 -9 .892 -9 .270 -9.317 -9.854 887 -7.430 -7.605 -6.787 -5.597 -7.340 -7 .474 -10.733 -2.700 53.561 1.00 9.21 -11.902 -2.403 51.652 1.00 5.93 -2.733 -1.204 -0.862 -1.880 -1.789 -1.878 -1.652 -1.629 -1.580 -0.015 0.781 0.106 -0.541 1.190 1 .059 2 .047 2.350 1 .496 1.146 2.133 -0.025 -0.789 -0.223 -1.650 -1.938 -1.816 0.031 0.731 -0.524 -1.062 -0.349 -1.272 -2.731 -3 .144 -2.765 -3 .852 1 .076 51. 066 51. 262 49.798 48.848 47.432 47.209 46.469 46.708 45.537 52.160 52.430 52.615 52.324 53.511 53 .872 54.874 54.483 56. 298 54.769 55.134 55.390 55.026 56.603 57.157 58.330 57.587 56.406 57.197 55.347 54.733 55.094 53.976 54.340 55.547 55.618 56.416 54.796 1.00 0.00 1.00 4.78 1.00 6.84 1.00 10.82 1.00 10.56 1.00 8.62 1.00 11.25 1.00 0.00 1.00 0.00 1.00 3.62 1.00 5.94 1.00 5.89 1.00 0.00 1.00 4.73 1.00 4.90 1.00 6.15 1.00 8.45 1.00 4.62 1.00 5.64 1.00 6.99 1.00 5.96 1.00 0.00 1.00 8.27 1.00 9.38 1.00 7.51 1.00 5.71 1.00 9.49 1.00 12.68 1.00 10.79 1.00 0.00 1.00 11.35 1.00 16.61 1.00 22.80 1.00 24.22 1.00 22.20 1.00 23.12 1.00 9.15 209 ATOM 2296 0 GLU 237 ATO 226 0 GLU 237 -6.380 1.498 55.156 1.00 12.17

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2297 N TYR 2298 H TYR 2299 CA TYR 2300 CB TYR 2301 CG TYR 2302 CD1 TYR.

2303 CEl TYR 2304 CD2 TYR 2305 CE2 TYR 2306 CZ TYR 2307 OH TYR 2308 HH TYR 2309 C TYR 2310 0 TYR 2311 N LEU 2312 H LEU 2313 CA LEU 2314 CB LEU 2315 CG LEU 2316 CD1 LEU 2317 CD2 LEU 2318 C LEU 2319 o LEU 2320 N LYS 2321 H LYS 2322 CA LYS 2323 CB LYS 2324 CG LYS 2325 CD LYS 2326 CE LYS 2327 NZ LYS 2328 HZ1 LYS 2329 HZ2 LYS 2330 HZ3 LYS 2331 C LYS 2332 0 LYS 2333 N LEU 2334 H LEU 238 238 238 238 238 238 238 238 238 238 238 238 238 238 239 239 239 239 239 239 239 239 239 240 240 240 240 240 240 240 240 240 240 240 240 240 241 241 -8.355 -9.205 -8.125 -9.226 -9.016 -8.241 -8.072 -9.619 -9.458 -8.686 -8.540 -9.060 -8.160 -7.335 -9 .113 -9.745 -9.276 -10.675 -11.814 -13 .168 -11. 696 -8 .170 -8.076 -7.360 -7.552 -6 .221 -5.709 -6.446 1.809 54.128 1.00 9.53 1.398 53.859 1.00 0.00 3.205 53.785 1.00 6.78 3.674 52.835 1.00 5.11 5.049 52.254 1.00 6.85 5.232 51.112 1.00 6.52 6.503 50.549 1.00 10.87 6.169 52.830 1.00 9.19 7.438 52.281 1.00 10.07 7.596 51.141 1.00 10.71 8.843 50.592 1.00 14.33 9.481 51.085 1.00 0.00 4.042 55.057 1.00 6.62 4.929 55.247 1.00 6.71 3.731 55.931 1.00 7.40 3.006 55.745 1.00 0.00 4.443 57.191 1.00 9.62 4.198 57.774 1.00 8.00 4.773 56.918 1.00 8.26 4.365 57.461 1.00 2.00 6.285 56.865 1.00 6.62 4.092 58.187 1.00 11.33 4.689 59.261 1.00 11.19 3.091 57.848 1.00 12.90 2.545 57.064 1.00 0.00 2--5 58.687 1.00 15.35 58.368 1.00 12.42 0.171 59.010 1.00 16.17 -5.570 -1.069 58.865 1.00 18.37 -6.272 -2.347 59.239 1.00 21.75 -5.382 -3.491 58.897 1.00 22.57 -4.536 -3 .458 59.499 1.00 0.00 -5.113 -3.415 57.895 1.00 0.00 -5.890 -4.386 59.045 1.00 0.00 -5.103 3.706 58.351 1.00 16.14 -4.316 4.084 59.212 1.00 18.31 -5.039 4.096 57.081 1.00 17.44 -5.702 3.764 56.447 1.00 0.00 -210 ATOM 2335 CA LEU ATOM 2336 CB LEU ATOM 2337 CG LEU ATOM 2338 CD1 LEU ATOM 2339 CD2 LEU ATOM 2340 C LEU ATOM 2341 O LEU ATOM 2342 N LYS ATOM 2343 H LYS ATOM 2344 CA LYS ATOM 2345 CB LYS ATOM 2346 CG LYS ATOM 2347 CD LYS ATOM 2348 CE LYS ATOM 2349 NZ LYS ATOM 2350 HZ1 LYS ATOM 2351 HZ2 LYS ATOM 2352 HZ3 LYS ATOM 2353 C LYS ATOM 2354 O LYS ATOM 2355 N ALA ATOM 2356 H ALA ATOM 2357 CA ALA ATOM 2358 CB ALA ATOM 2359 C ALA ATOM 2360 O ALA ATOM 2361 N ASP ATOM 2362 H ASP ATOM 2363 CA ASP ATOM 2364 CB ASP ATOM 2365 CG ASP ATOM 2366 OD1 ASP ATOM 2367 OD2 ASP ATOM 2368 C ASP ATOM 2369 O ASP ATOM 2370 N GLY ATOM 2371 H GLY ATOM 2372 CA GLY ATOM 2373 C GLY 241 241 241 241 241 241 241 242 242 242 242 242 242 242 242 242 242 242 242 242 243 243 243 243 243 243 244 244 244 244 244 244 244 244 244 245 245 245 245 -4.023 -3.838 -3.473 -3.580 -2.072 -4.336 -3.430 -5.608 -6.313 -5.996 -5.892 -6.778 -6.367 -5.120 -4.732 -4.553 -5.490 -3.864 -7.395 -8.313 -7.540 -6.733 -8.814 -8.690 -10.018 -11.102 -9.834 -8.942 -10.888 -11.023 -11.885 -12.653 -11.802 -12.245 -13.293 -12.219 -11.383 -13.447 -13.591 5.015 56.584 1.00 20.78 4.814 55.080 1.00 23.79 3.389 54.637 1.00 29.02 3.258 53.116 1.00 31.10 3.023 55.123 1.00 29.32 6.479 56.882 1.00 20.10 7.271 57.127 1.00 22.00 6.849 56.829 1.00 19.66 6.208 56.582 1.00 0.00 8.224 57.114 1.00 19.53 9.082 55.844 1.00 22.06 8.639 54.688 1.00 24.44 9.308 53.386 1.00 24.79 8.664 52.808 1.00 23.03 9.280 51.518 1.00 23.85 10.291 51.657 1.00 0.00 9.155 50.820 1.00 0.00 8.824 51.169 1.00 0.00 8.279 57.716 1.00 16.00 7.645 57.218 1.00 15.48 9.047 58.793 1.00 18.41 9.494 59.123 1.00 0.00 9.192 59.507 1.00 18.23 10.251 60.597 1.00 15.43 9.497 58.620 1.00 18.79 8.965 58.839 1.00 21.98 10.408 57.669 1.00 18.70 10.786 57.579 1.00 0.00 10.804 56.737 1.00 19.33 9.741 55.633 1.00 19.97 10.197 54.466 1.00 23.11 9.359 53.958 1.00 27.17 11.374 54.045 1.00 24.99 11.108 57.402 1.00 19.28 10.622 56.969 1.00 19.97 11.934 58.445 1.00 19.45 12.294 58.773 1.00 0.00 12.295 59.133 1.00 16.82 11.656 60.499 1.00 15.03 211 ATOM 2374 0 GLY 245 -14.259 12.202 61.369 1.00 16.04 ATOM 2375 N LEU 246 -13.000 10.482 60.676 1.00 13.51 ATOM 2376 H LEJ 246 -12.517 10.063 59.930 1.00 0.00 ATOM 2377 CA LEU 246 -13.069 9.791 61.951 1.00 12.38 ATOM 2378 CB LEU 246 -12.484 8.377 61.836 1.00 10.62 ATOM 2379 CG LEU 246 -13.117 7.342 60.907 1.00 8.08 ATOM 2380 CD1 LEU 246 -12.370 6.037 61.059 1.00 7.46 ATOM 2381 CD2 LEU 246 -14.568 7.138 61.240 1.00 9.01 ATOM 2382 c LET) 246 -12.311 10.576 63.019 1.00 12.72 ATOM 2383 0 LEU 246 -11.451 11.411 62.704 1.00 12.81 ATOM 2384 N ILE 247 -12.627 10.288 64.279 1.00 13.47 ATOM 2385 H ILE 247 -13.329 9.624 64.457 1.00 0.00 ATOM 2386 CA ILE 247 -11.995 10.947 65.418 1.00 13.85 ATOM 2387 c3 ILE 247 -12.762 10.635 66.734 1.00 15.16 1 5 ATOM 2388 CG2 ILE 247 -12.608 9.163 67.118 1.00 12.79 ATOM 2389 CG1 ILE 247 -12.268 11.529 67.869 1.00 15.17 *ATOM 2390 CD ILE 247 -12.636 12.970 67.713 1.00 18.15 .*ATOM 2391 c ILE 247 -10.542 10.502 65.550 1.00 15.68 **ATOM 2392 o ILE 247 -9.709 11.218 66.100 1.00 15.94 ATOM 2393 N TYR 248 -10.244 9.320 65.-020 1.00 17.12 *ATOM 2394 H TYR 248 -10.933 8.784 64.573 1.00 0.00 ATOM 2395 CA TYR 248 -8.902 8.760 65.071 1.00 18.04 ATOM 2396 CS TYR 248 -8.623 8.221 66.478 1.00 19.67 ATOM 2397 CG TYR 248 -7.160 8.036 66.808 1.00 22.04 ATOM 2398 CD1l TYR 248 -6.666 6.795 67.194 1.00 21.97 ATOM 2399 CZI TYR 248 -5.330 6.630 67.539 1.00 24.30 *ATOM 2400 CD2 TYR 248 -6.277 9.113 66.770 1.00 25.29 *ATOM 2401 CE2 TYR 248 -4.940 8.962 67.113 1.00 26.21 ATOM 2402 C Z TYR 248 -4.471 7.720 67.498 1.00 26.00 ATOM 2403 OH TYR 248 -3.147 7.572 67.853 1.00 27.81 ATOM 2404 HH TYR 248 -2.695 8.422 67.810 1.00 0.00 ATOM 2405 C TYR 248 -8.826 7.618 64.053 1.00 18.31 ATOM 2406 0 TYR 248 -9.839 6.992 63.737 1.00 15.87 ATOM 2407 N CYS 249 -7.625 7.363 63.543 1.00 18.92 ATOM 2408 H CYS 249 -6.862 7.889 63.852 1.00 0.00 ATOM 2409 cAm CYS 249 -7.402 6.305 62.561 1.00 22.24 ATOM 2410 cS BCYS 249 -5.996 6.413 61.961 1.00 25.63 ATOM 2411 s G CYS 249 -5.786 7.673 60.701 1.00 35.34 ATOM 2412 c CYS 249 -7.554 4.915 63.162 1.00 21.45 212 ATOM 2413 0 CYS 249 ATM 41 0 CY 29 -7.292 4.709 64.350 1.00 22.48 *5

S

S

S

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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25 ATOM

ATOM

ATOM

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2414 N LZU 2415 H LEU 2416 CA LEU 2417 CB LEU 2418 CG LEU 2419 CD1 LEU 2420 CD2 LEU 2421 C LEU 2422 0 LET) 2423 N LYS 2424 H LYS 2425 CA LYS 2426 CB LYS 2427 CG LYS 2428 CD LYS 2429 CE LYS 2430 NZ LYS 2431 HZ1 LYS 2432 HZ2 LYS 2433 HZ3 LYS 2434 c LYS 2435 0 LYS 2436 N DILU 2437 H GLU 2438 CA GLU 2439 CB GLU 2440 CG GLU 2441 CD GLU 2442 OE1 GLU 2443 0E2 GLU 2444 c GLU 2445 0 GLU 2446 N ALA 2447 H ALA 2448 CA ALA 2449 CB ALA 2450 C ALA 250 250 250 250 250 250 250 250 250 251 251 251 251 2 51 251 251 251 251 251 251 251 251 252 252 2 52 2-52 25 2 252 252 252 252 253 253 253 253 253 -7.940 -8.101 -8.104 -8.828 -10.355 -10.924 -10.909 -6.717 -5.874 -6.469 -7.187 -5.167 -4 .605 -4.299 -3.054 -2.720 -3.778 -4.678 -3.889 -3.501 -5.217 -5.026 -5.516 -5.766 -5.565 -5.012 -3 .569 -3.268 -3.435 -2.858 -6 .978 -7.929 -7 .108 -6.318 -8.395 -8.343 -8.747 3.963 4.207 2.579 1.801 1.767 2.936 1.703 1.999 2.037 1.496 1.486 0.937 1.601 3.082 3.298 4.776 5.512 5.441 5.099 6.511 -0.574 -1.329 -1.013 -0.390 -2.430 -2.671 -2.212 -1.746 -2.543 -0.575 -2.977 -2.360 -4.132 -4.560 -4.786 -5.756 -5.537 62.321 61. 383 62.735 61.643 61. 685 62.474 60.275 62.958 62.064 64.158 64.818 64.479 65.737 65.586 64.739 64.587 63 .835 64.346 62.891 63.746 64. 657 63.703 65.871 66.588 66 .174 67.577 67.765 69.186 70.137 69.348 66.071 66.550 65.432 65.066 65.278 64.123 66.555 1.00 1.00 1.0 1.01 1.0 1.0O 1.0OC 1.0 1.00C 1.00C 1.00 1.00 I. 00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1 .00 1.00 1 .00 1 .00 1.00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 0 18.62 0 14.55 0 15.19 015.11 10.15 19.97 20.94 20.78 0.00 22 .81 22.15 27.38 33.83 36.07 39.79 0 .00 0 .00 0 .00 24.22 27.36 24.92 0.00 27 .42 32.86 43.35 49.35 51.97 50.94 26.08 25 .56 24.39 0.00 25 .57 24.04 27.38 19.48 0. 00 ATOM 2451 0 ALA 253 -7.876 -6.121 67.194 1.00 27.58 .213

ATOM

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15 ATOM

ATOM

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20 ATOM

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ATOM

ATOM

ATOM

2452 N 2453 H 2454 CA 2455 CB 2456 SG 2457 C 2458 O 2459 N 2460 CD 2461 CA 2462 CB 2463 CG 2464 C 2465 O 2466 N 2467 H 2468 CA 2469 CB 2470 CG 2471 OD1 2472 ND2 2473 HD21 2474 HD22 2475 C 2476 O 2477 OT 2478 C 2479 O 2480 HT1 2481 HT2 2482 N 2483 HT3 2484 CA 2485 N 2486 H 2487 CA 2488 C3 2489 CG

CYS

CYS

CYS

CYS

CYS

CYS

CYS

PRO

PRO

PRO

PRO

PRO

PRO

PRO

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ASN

GLY

GLY

GLY

GLY

GLY

GLY

GLY

LEU

LEU

LEU

LEU

LEU

254 254 254 254 254 254 254 255 255 255 255 255 255 255 256 256 256 256 256 256 256 256 256 256 256 256 301 301 301 301 301 301 301 302 302 302 302 302 -10.014 -5.479 -10.650 -4.969 -10.492 -6.198 -11.780 -5.561 -12.375 -6.219 -10.767 -7.569 -11.755 -7.746 -9.875 -8.542 -8.830 -8.385 -9.899 -9.928 -8.601 -10.493 -8.523 -9.817 -11.081 -10.826 -12.133 -10.365 -10.888 -12.119 -10.045 -12.478 -11.871 -13.161 -12.685 -13.504 -13.596 -12.375 -14.807 -12.413 -13.021 -11.366 -12.055 -11.405 -13.555 -10.623 -11.085 -14.393 -11.316 -14.859 -10.212 -14.846 -28.599 6.538 -28.689 7.658 -29.755 6.289 -30.909 6.664 -30.363 5.888 -30.941 5.100 -29.470 5.406 -27.760 6.248 -27.741 5.327 -26.861 7.240 -26.840 7.061 -26.726 8.304 -27.093 7.919 66.949 66.417 68.125 68.652 70.229 67.511 66.799 67.759 68.790 67.273 67.840 69.164 67.628 68.071 67.377 67.027 67.655 66.400 65.964 66.187 65.336 65.202 65.004 68.105 69.241 67.326 66.632 66.126 64.304 65.460 65.043 64.692 66.131 67.620 67.985 68.203 69.721 70.601 72.026 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 31.53 0.00 32.99 33.76 27.18 36.46 36.39 41.03 42.01 44.44 45.11 43.82 46.86 47.30 51.27 0.00 53.98 54.04 53.84 53.28 52.61 0.00 0.00 55.88 56.61 57.33 34.96 35.59 0.00 0.00 38.32 0.00 35.83 32.78 0.00 28.83 30.89 35.75 34.77 ATOM 2490 CD1 LEU 302 214 ATOM 2491 CD2 LEU ATOM 2492 c LEU ATOM 2493 0 LEU ATOM 2494 N PTY ATOM 2495 H PTY ATOM 2496 CA PTY ATOM 2497 CB PTY ATOM 2498 CG PTY ATOM 2499 CD1 PTY 1 0 ATOM 2500 CEl PTY ATOM 2501 CD2 PTY ATOM 2502 CE2 PTY ATOM 2503 CZ PTY ATOM 2504 OH PTY 1 5 ATOM 2505 ORi PTY *ATOM 2506 0R2 PTY ATOM 2507 0R3 PTY *:*ATOM 2508 PR PTY :ATOM 2509 c PTY ATOM 2510 0 PTY *ATOM 2511 N ASN *ATOM 2512 H ASN ATOM 2513 CA ASN *ATOM 2514 CB ASN 25 ATOM 2515 CG ASN ATOM 2516 ODi ASN ATOM 2517 ND2 ASN ATOM 2518 HD21 ASN ATOM 2519 HD22 ASN ATOM 2520 C ASN ATOM 2521 0 ASN ATOM 2522 N GLU ATOM 2523 H GLU ATOM 2524 CA GLU ATOM 2525 CB GLU ATOM 2526 CG GLU ATOM 2527 CD GLU ATOM 2528 OE1 GLU ATOM 2529 0E2 GLU 302 302 302 303 303 303 303 303 303 303 303 303 303 303 303 303 303 303 303 303 304 304 304 304 304 304 304 304 304 304 304 305 305 305 305 305 305 305 -25.328 8.914 70.520 1.00 36.69 -25.465 7.028 67.613 1.00 24.31 -24.620 6.352 68.205 1.00 22.95 -25.236 7.580 66.427 1.00 20.12 -25.916 8.143 65.984 1.00 0.00 -23.952 7.422 65.758 1.00 17.44 -24.137 6.739 64.399 1.00 15.28 -24.685 5.341 64.531 1.00 11.57 -23.836 4.247 64.652 1.00 14.15 -24.342 2.959 64.848 1.00 14.74 -26.053 5.121 64.602 1.00 14.21 -26.570 3.847 64.796 1.00 14.14 -25.714 2.772 64.918 1.00 15.16 -26.257 1.519 65.078 1.00 16.76 -27.377 1.226 67.142 1.00 15.99 -24.983 1.051 67.202 1.00 15.90 -26.327 -0.668 66.144 1.00 16.79 -26.181 0.776 66.437 1.00 13.90 -23.217 8.735 65.605 1.00 16.36 -23.831 9.795 65.484 1.00 19.96 -21.895 8.660 65.620 1.00 15.34 -21.498 7.781 65.684 1.00 0.00 -21.062 9.841 65.492 1.00 17.74 -19.676 9.569 66.078 1.00 17.48 -19.731 9.186 67.544 1.00 21.95 -19.541 10.024 68.421 1.00 25.74 -20.008 7.918 67.818 1.00 20.37 -20.117 7.310 67.059 1.00 0.00 -20.130 7.655 68.755 1.00 0.00 -20.959 10.277 64.033 1.00 18.33 -20.992 9.450 63.118 1.00 19.64 -20.917 11.583 63.814 1.00 19.12 -20.936 12.208 64.568 1.00 0.00 -20.802 12.114 62.463 1.00 22.88 -21.555 13.441 62.336 1.00 28.84 -23.071 13.318 62.315 1.00 37.99 -23.767 14.669 62.216 1.00 43.48 -24.877 14.800 62.775 1.00 46.82 -23.214 15.597 61.580 1.00 45.74 215

ATOM

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ATOM

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ATOM

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ATOM

2530 C GLU 2531 0 GLU 2532 N LEU 2533 H LEU 2534 CA LEU 2535 CB LET) 2536 CG LET) 2537 CD1 LET) 2538 CD2 LET) 2539 C LET) 2540 0 LET) 2541 N GLN 2542 H GLN 2543 CA GLN 2544 CB GLN 2545 CG GLN 2546 CD GLN 2547 QE1 GLN 2548 NE2 GLN 2549 HE21 GLN 2550 HE22 GLN 2551 c GLN 2552 0 GLN 2553 N LYS 2554 H LYS 2555 CA LYS 2556 CB LYS 2557 CG LYS 2558 CD LYS 2559 CE LYS 2560 NZ LYS 2561 HZ1 LYS 2562 HZ2 LYS 2563 HZ3 LYS 2564 C LYS 2565 0 LYS 2566 N ASP 2567 H ASP 2568 CA ASP 305 305 306 306 306 306 306 306 306 306 306 307 307 307 307 307 307 307 307 307 307 307 307 308 308 308 308 308 308 308 308 308 308 308 308 308 309 309 309 -19.329 12.339 62.158 1.00 21.37 -18.504 12.412 63.068 1.00 21.67 -19.002 12.437 60.878 1.00 19.52 -19.698 12.382 60.192 1.00 0.00 -17.628 12.667 60.469 1.00 17.30 -17.451 12.319 58.992 1.00 16.06 -17.537 10.838 58.627 1.00 12.83 -17.235 10.669 57.151 1.00 16.69 -16.555 10.040 59.462 1.00 10.12 -17.251 14.119 60.706 1.00 17.36 -18.070 15.014 60.519 1.00 17.26 -16.019 14.341 61.147 1.00 18.44 -15.442 13.576 61.304 1.00 0.00 -15.509 15.685 61.396 1.00 23.01 -14.187 15.618 62.167 1.00 25.06 -14.138 14.590 63.278 1.00 29.12 -14.549 15.148 64.618 1.00 30.60 -15.721 15.453 64.849 1.00 34.83 -13.583 15.285 65.517 1.00 31.12 -12.680 15.007 65.262 1.00 0.00 -13.830 15.662 66.384 1.00 0.00 -15.219 16.248 60.017 1.00 24.16 -14.087 16.149 59.546 1.00 20.19 -16.245 16.781 59.354 1.00 30.35 -17.125 16.772 59.791 1.00 0.00 -16.110 17.348 58.004 1.00 33.42 -17.486 17.666 57.388 1.00 34.90 -18.534 16.560 57.453 1.00 35.45 -19.567 16.860 58.532 1.00 36.09 -20.215 18.229 58.316 1.00 37.61 -21.196 18.594 59.391 1.00 37.36 -20.711 18.602 60.310 1.00 0.00 -21.961 17.891 59.403 1.00 0.00 -21.589 19.535 59.193 1.00 0.00 -15.296 18.632 58.059 1.00 34.50 -15.720 19.675 57.561 1.00 36.22 -14.110 18.542 58.637 1.00 34.96 -13.714 17.697 58.867 1.00 0.00 -13.247 19.684 58.786 1.00 40.11 p

ATOM

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ATOM

ATOM

216 ATOM 2569 CB ASP 309 ATM 56 C AP 09 -13.833 20.653 59.825 1.00 43.76 ATOM 2570 CG ASP 309 -12.937 21.857 60.076 1.00 49.11 ATOM 2571 ODI ASP 309 -12.285 21.902 61.147 1.00 50.11 ATOM 2572 OD2 ASP 309 -12.878 22.752 59.198 1.00 53.22 ATOM 2573 C ASP 309 -11.919 19.147 59.266 1.00 41.03 ATOM 2574 0 ASP 309 -11.021 18.889 58.468 1.00 42.47 ATOM 2575 N LYS 310 -11.848 18.882 60.565 1.00 42.27 ATOM 2576 H LYS 310 -12.637 19.008 61.117 1.00 0.00 ATOM 2577 CA LYS 310 -10.634 18.385 61.192 1.00 43.52 ATOM 2578 CB LYS 310 -10.941 17.848 62.595 1.00 42.96 ATOM 2579 CG LYS 310 -11.586 18.868 63.525 1.00 42.02 ATOM 2580 CD LYS 310 -11.779 18.312 64.933 1.00 41.98 ATOM 2581 CE LYS 310 -10.445 18.138 65.654 1.00 41.82 ATOM 2582 NZ LYS 310 -10.613 17.544 67.012 1.00 40.90 1 ATOM 2583 HZ1 LYS 310 -11.030 16.595 66.920 1.00 0.00 ATOM 2584 HZ2 LYS 310 -11.238 18.146 67.589 1.00 0.00 .ATOM 2585 HZ3 LYS 310 -9.684 17.470 67.471 1.00 0.00 *ATOM 2586 C LYS 310 -9.895 17.331 60.372 1.00 43.43 ATOM 2587 0 LYS 310 -8.664 17.323 60.353 1.00 46.61 ATOM 2588 N ARC 311 -10.629 16.461 59.680 1.00 42.01 *ATOM 2589 H ARC 311 -11.604 16.507 59.665 1.00 0.00 ATOM 2590 CA ARC 311 -9.982 15.415 58.891 1.00 42.72 ATOM 2591 CB ARG 311 -10.023 14.081 59.644 1.00 44.23 *ATOM 2592 CG ARG 311 -10.718 14.119 61.003 1.00 45.03 ATOM 2593 CD ARG 311 -9.748 14.485 62.100 1.00 45.93 ATOM 2594 NE ARC 3 11 -10.418 14.685 63 .378 1.00 48.24 ATOM 2595 HE ARG 311 -11.373 14.913 63.367 1.00 0.00 ATOM 2596 C Z ARC 311 -9.818 14.577 64.561 1.00 51.76 ATOM 2597 NH1 ARC 311 -8.530 14.264 64.635 1.00 54.63 ATOM 2598 H11 ARC 311 -7.990 14.102 63.808 1.00 0.00 ATOM 2599 HH12 ARC 311 -8.100 14.179 65.535 1.00 0.00 ATOM 2600 NH2 ARG 311 -10.503 14.798 65.675 1.00 53.00 ATOM 2601 HH21 ARC 311 -11.469 15.047 65.619 1.00 0.00 ATOM 2602 HH22 ARC 311 -10.059 14.715 66.567 1.00 0.00 ATOM 2603 c ARC 311 -10.555 15.212 57.491 1.00 42.09 ATOM 2604 0 ARC 311 -11.725 14.856 57.346 1.00 40.29 ATOM 2605 N ALA 312 -9.714 15.389 56.469 1.00 44.22 ATOM 2606 H ALA 312 -8.797 15.704 56.637 1.00 0.00 ATOM 2607 CA ALA 312 -10.130 15.204 55.077 1.00 45.11 217 ATOM 2608 CB ALA 312 ATM 60 C AA 12 -11.440 15.947 54.818 1.00 46.77 ATOM 2609 C ALA 312 -9.086 15.616 54.024 1.00 47.98 ATOM 2610 0 ALA 312 -8.221 16.462 54.283 1.00 50.03 ATOM 2611 N GLU 313 -9.168 14.980 52.852 1.00 45.77 ATOM 2612 H GLU 313 -9.890 14.332 52.717 1.00 0.00 ATOM 2613 CA GLU 313 -8.306 15.252 51.693 1.00 43.28 ATOM 2614 CB GLU 313 -7.513 14.005 51.283 1.00 46.48 ATOM 2615 CG GLU 313 -6.297 13.659 52.143 1.00 46.91 ATOM 2616 CD GLU 313 -5.519 12.454 51.605 1.00 46.04 ATOM 2617 OE1 GLU 313 -6.023 11.761 50.692 1.00 44.53 ATOM 2618 0E2 GLU 313 -4.397 12.198 52.097 1.00 45.88 ATOM 2619 c GLU 313 -9.314 15.575 50.583 1.00 42.06 ATOM 2620 0 GLU 313 -10.513 15.680 50.869 1.00 45.47 ATOM 2621 N ALA 314 -8.870 15.668 49.329 1.00 31.51 ATOM 2622 H ALA 314 -7.925 15.544 49.104 1.00 0.00 ATOM 2623 CA ALA 314 -9.801 15.967 48.239 1.00 27.16 ATOM 2624 CB ALA 314 -10.156 17.447 48.238 1.00 25.68 ATOM 2625 c ALA 314 -9.311 15.545 46.858 1.00 24.26 ATOM 2626 0 ALA 314 -8.204 15.896 46.447 1.00 26.34 ATOM 2627 N PTY 315 -10.127 14.766 46.158 1.00 18.14 ATOM 2628 H PTY 315 -11.001 14.528 46.522 1.00 0.00 ATOM 2629 CA PTY 315 -9.787 14.306 44.814 1.00 17.87 ATOM 2630 CB PTY 315 -10.410 12.934 44.531 1.00 16.23 ATOM 2631 CG PTY 315 -9.653 11.782 45.147 1.00 13.44 25 ATOM 2632 CD1 PTY 315 -8.546 11.233 44.504 1.00 10.57 ATOM 2633 CE1 PTY 315 -7.821 10.199 45.083 1.00 12.46 ATOM 2634 CD2 PTY 315 -10.024 11.261 46.388 1.00 14.63 *ATOM 2635 C 2 PTY 315 -9.308 10.226 46.977 1.00 12.19 *ATOM 2636 CZ PTY 315 -8.207 9.702 46.319 1.00 14.21 ATOM 2637 OH PTY 315 -7.508 8.671 46.896 1.00 10.17 ATOM 2638 ORi PTY 315 -6.491 9.535 48.913 1.00 12.42 ATOM 2639 0R2 PTY 315 -5.416 9.978 46.850 1.00 12.44 ATOM 2640 0R3 PTY 315 -5.389 7.728 47.750 1.00 8.98 ATOM 2641 PR. PTY 315 -6.156 8.991 47.608 1.00 11.81 ATOM 2642 C PTY 315 -10.273 15.318 43.781 1.00 18.42 ATOM 2643 0 PTY 315 -11.328 15.928 43.950 1.00 18.97 ATOM 2644 N SER 316 -9.500 15.502 42.718 1.00 18.72 ATOM 2645 H SER 316 -8.700 14.957 42.602 1.00 0.00 ATOM 2646 CA SER 316 -9.871 16.443 41.676 1.00 17.28 218

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1 5 ATOM

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25 ATOM

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2647 CB SER 2648 OG SER 2649 HG SER 2650 C SER 2651 0 SER 2652 N GLU 2653 H GLU 2654 CA GLU 2655 CB GLU 2656 CG GLU 2657 CD GLU 2658 0E1 GLU 2659 0E2 GLU 2660 C GLU 2661 0 GLU 2662 N ILE 2663 H ILE 2664 CA ILE 2665 CB ILE 2666 CG2 ILE 2667 CG1 ILE 2668 CD ILE 2669 C ILE 2670 0 ILE 2671 N GLY 2672 H- GLY 2673 CA GLY 2674 C GLY 2675 o GLY 2676 OT GLY 2677 0H2 H20 2678 Hi H20 2679 H2 H20 2680 0H2 H20 2681 Hi H20 2682 H2 H20 2683 0H2 H20 2684 Hi H20 2685 H2 H20 316 316 316 316 316 317 317 317 317 317 317 317 317 317 317 318 318 318 318 318 318 318 318 318 319 319 319 319 319 319 501 501 501 502 502 502 503 503 503 -8.642 16.849 40.874 1.00 16.40 -7.653 17.434 41.705 1.00 23.25 -7.610 16.969 42.563 1.00 0.00 -10.895 15.799 40.762 1.00 17.80 -11.065 14.581 40.763 1.00 18.76 -11.578 16.619 39.978 1.00 21.98 -11.430 17.585 39.995 1.00 0.00 -12.577 16.113 39.048 1.00 26.81 -13.956 16.070 39.718 1.00 28.26 -14.954 15.164 39.010 1.00 34.96 -16.232 14.947 39.803 1.00 40.11 -17.320 14.948 39.180 1.00 42.24 -16.153 14.763 41.041 1.00 42.30 -12.594 17.020 37.826 1.00 27.50 -12.160 18.170 37.908 1.00 28.44 -12.985 16.479 36.676 1.00 30.01 -13.247 15.532 36.647 1.00 0.00 -13.052 17.287 35.463 1.00 32.57 -12.991 16.428 34.176 1.00 31.13 -13.313 17.282 32.955 1.00 30.52 -11.598 15.824 34.009 1.00 29.07 -11.436 15.012 32.736 1.00 29.47 -14.368 18.051 35.510 1.00 36.48 -15.438 17.474 35.299 1.00 37.22 -14.281 19.335 35.841 1.00 40.36 -13.427 19.760 36.061 1.00 0.00 -15.461 20.174 35.922 1.00 45.03 -15.094 21.595 36.305 1.00 47.82 -14.951 22.445 35.395 1.00 50.47 -14.941 21.860 37.516 1.00 49.68 -16.699 6.688 54.302 1.00 10.61 -16.511 6.418 53.393 1.00 0.00 -16.240 7.548 54.364 1.00 0.00 -7.254 -1.610 48.935 1.00 17.08 -6.444 -2.072 49.204 1.00 0.00 -7.404 -0.987 49.670 1.00 0.00 -8.059 0.563 50.782 1.00 14.29 -8.518 0.793 49.971 1.00 0.00 -8.748 0.792 51.423 1.00 0.00 219 ATOM 2686 0H2 H20 504 -6.332 5.449 46.114 1.00 17.64 ATOM 2687 Hi H20 504 -5.403 5.611 45.858 1.00 0.00 ATOM 2688 H2 H20 504 -6.621 6.329 46.396 1.00 0.00 ATOM 2689 OH2 H20 505 -15.290 -6.823 51.705 1.00 5.22 ATOM 2690 H1 H2O 505 -15.750 -6.668 50.860 1.00 0.00 ATOM 2691 H2 H20 505 -14.376 -6.905 51.376 1.00 0.00 ATOM 2692 082 H20 506 -7.617 -1.501 46.161 1.00 17.32 ATOM 2693 Hi H20 506 -7.518 -1.538 47.137 1.00 0.00 ATOM 2694 H2 H20 506 -6.696 -1.494 45.885 1.00 0.00 ATOM 2695 0H2 H20 507 -3.651 7.250 49.955 1.00 15.71 ATOM 2696 HI 820 507 -4.520 7.609 50.184 1.00 0.00 ATOM 2697 H2 H20 507 -3.891 6.758 49.154 1.00 0.00 ATOM 2698 082 H20 508 -19.945 3.732 76.340 1.00 29.44 ATOM 2699 Hi 820 508 -20.832 3 .744 75.964 1.00 0.00 1 5 ATOM 2700 H2 1120 508 -19.954 4.642 76.685 1.00 0.00 ATOM 2701 0112 820 509 10.902 10.846 41.751 1.00 27.04 ATOM 2702 H 1 820 509 10.681 10.574 40.852 1.00 0.00 ATOM 2703 82 820 509 10.412 11.675 41.818 1.00 0.00 ATOM 2704 082 H20 510 -18.163 -5.347 50.709 1.00 9.29 20 ATOM 2705 81 820 510 -18.386 -6.283 50.714 1.00 0.00 ATOM 2706 H2 H20 510 -19.045 -4.964 50.769 1.00 0.00 ATOM 2707 082 H20 511 -3.361 4.879 45.414 1.00 16.59 ATOM 2708 Hl H20 511 -3.647 4.007 45.146 1.00 0.00 ATOM 2709 H2 H20 511 -2.506 4.681 45.802 1.00 0.00 25 ATOM 2710 082 820 512 -15.018 8 .551 55.143 1.00 25.00 ATOM 2711 81 820 512 -14.918 7.843 55.793 1.00 0.00 ATOM 2712 82 820 512 -14.547 9.270 55.600 1.00 0.00 **ATOM 2713 082 820 513 -4.825 -3.898 46.077 1.00 26.22 **ATOM 2714 Hl 820 513 -4.880 -3.377 46.901 1.00 0.00 ATOM 2715 H2 820 513 -4.485 -3.251 45.428 1.00 0.00 ATOM 2716 082 820 514 -22.319 7.998 61.532 1.00 14.50 ATOM 2717 H1 820 514 -21.517 8.530 61.422 1.00 0.00 ATOM 2718 F2 820 514 -22.478 8.172 62.465 1.00 0.00 ATOM 2719 082 820 515 -10.803 5.341 41.005 1.00 25.05 ATOM 2720 H1 820 515 -10.171 5.135 40.303 1.00 0.00 ATOM 2721 82 820 515 -10.270 5.263 41.804 1.00 0.00 ATOM 2722 082 820 516 0.902 5.902 27.902 1.00 36.64 ATOM 2723 F1 820 516 0.214 6.451 28.280 1.00 0.00 ATOM 2724 82 820 516 1.440 6.522 27.390 1.00 0.00 220 ATOM 2725 OH2 H2o 517 ATOM 272 0H2H20 517-4.715 -2.823 48.594 1.00 17.95

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1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2726 2727 2728 2729 2730 2731 2732 2733 2734 2735 2736 2737 2738 2739 2740 2741 2742 2743 2744 2745 2746 2747 2748 2749 2750 2751 2752 2753 2754 2755 2756 2757 2758 2759 2760 2761 2762 2763 Hi H2 0H2 Hl H2

OH:

Hl H2

OH:

Hl H2 OH2 Hl H2 0H2 Hi H2 0H2 Hi H2 0H2 Hi H2 OH2 Hi H2 OH2 Hi H2 0H2 Hl H2 0H2 Hl H2 0H2 1-i H2 H20 H20 2 H20 H20 H20 H20 H20 H2 0 H20 H20 H20 H20 H20 H20 H2 0 H20 H20 H2 0 H120 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H2 0 H20 H20 517 517 518 518 518 519 519 519 520 520 520 521 521 521 522 522 522 523 523 523 524 524 524 525 z-2 5 5 25 526 526 526 527 527 527 528 528 528 529 529 529 471 93: -2 4. 8 0 -25. 33f -24.36E -7 49C -7.799 -6.561 -12.970 -12.945 -12.514 -11. 261 -11.026 -11.878 -16.253 -16.330 -16.945 -13.184 -13.959 -12.455 6.370 5 .423 6.738 -8.942 -8.594 -8.778 -15.180 -15.373 -14.575 4.557 4.963 5.249 0.327 0.588 -0.242 6.903 7.219 5.950 5 -1.913 3 -3.025 3 12.426 311.990 111.668 -3.895 -3.087 -3.711 1.075 0.105 1.300 10.026 10.800 9.547 9 .623 10.315 9.935 -18.559 -18.613 -18.533 1.830 1.688 0.978 6.660 7.220 7 .191 4.706 4.421 5.433 22.831 22.258 22.752 -18 .441 -18.051 -17.781 14.794 15.307 14 .776 48.357 49.141 65.782 66.447 65.372 44.639 45.072 44.492 39.173 39.195 39.992 31. 185 30.672 30.622 47.575 46.911 48.191 49.110 48 .542 48.480 43.428 43 .475 43.159 44 .772 44.081 45.563 44.777 45 .677 44.939 38.913 38.254 39 .588 40.849 40.013 41.246 51.066 50.322 50.943 1.00 0.00 1.0 1.0i 1.01 1.01 1.0O 1.00C 1.00C 1.00C 1.00 1.00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 0 0.00 0 40.32 0 0.00 0 0.00 17.54 0.00 0.00 I19.76 0.00 0.00 20.36 0.00 0.00 22. 54 0.00 0.00 32.97 0.00 0.00 20.14 0.00 0.00 32.99 0.00 0.00 35.71 0.00 0.00 25.19 0.00 0.00 63 .62 0.00 0.00 29 .24 0.00 0.00 221 ATOM 2764 OH2 H20 530 ATM 76 H2H2 50 -7.974 -1.103 42.817 1.00 34.83 s..

09 0 00*0 0 000.

sees.: 0

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2765 2766 2767 2768 2769 2770 2771 2772 2773 2774 2775 2776 2777 2778 2779 2780 2781 2782 2783 2784 2785 2786 2787 2788 2789 2790 2791 2792 2793 2794 2795 2796 2797 2798 2799 2800 2801 2802 Hl H20 H2 H20 0H2 H20 HI H20 H2 H20 0M2 H20 Hl H20 H2 H20 0H2 H120 Hl H20 H2 H120 0H2 H120 Hl H20 H2 H120 0H2 H120 Hl H20 H2 H20 0112 H20 Hl H120 H2 H20 0H2 H120 Hl H120 H2 H20 0H2 H120 Hi H120 H2 H120 0112 H20 Hl H20 H2 H120 0H2 H120 Hl H120 H2 H120 0H2 H20 Hl H20 H2 H120 0H2 H120 Hi H120 H2 H120 530 530 531 531 531 532 532 532 533 533 533 535 535 535 536 536 536 537 537 537 538 538 538 539 539 539 540 540 540 541 541 541 542 542 542 543 543 543 -7.354 -8.438 -21. 992 -22 .876 -22.202 -0.211 -1.107 -0.184 -14.231 -14 .283 -13 .463 -24.946 -24.728 -24.390 -25 .179 -25.799 -24.887 -1.848 -2.268 -2.023 -20.606 -19.935 -21.387 -6.036 -6.570 -0.435 -1.272 6.566 6.479 7 .118 -0.329 -0.247 0.393 14.927 14.056 14. 883 -4 .413 -4.688 -5.033 -8.028 -8.497 -7.298 9 .665 8.825 9.739 -24 .004 -24.681 -24.399 -10.488 -11 .253 43.127 43 .650 69.376 68.981 70.144 27.193 27.545 26.558 55.731 55.341 56.317 65.364 64.466 65 .854 64 .357 63.785 63 .794 51.881 51.657 52 .829 46.721 46.905 47 .126 42.753 42.552 43.597 50.060 50.173 50.953 62.249 63 .043 61.567 49 .390 50.147 48.776 37.785 38.496 37.011 1.00 0.00 1.00 0.00 1.00 33.58 1.00 0.00 1.00 0.00 1.00 35.34 1.00 0.00 1.00 0.00 1.00 22.94 1.00 0.00 1.00 0.00 1.00 21.19 1.00 0.00 1.00 0.00 1.00 22.68 1.00 0.00 1.00 0.00 1.00 19.01 1.00 0.00 1.00 0.00 1.00 48.06 1.00 0.00 1.00 0.00 1.00 24.63 1.00 0.00 1.00 0.00 1.00 44.45 1.00 0.00 1.00 0.00 1.00 38.68 1.00 0.00 1.00 0.00 1.00 42.13 1.00 0.00 1.00 0.00 1.00 44.00 1.00 0.00 1.00 0.00 -5.637 -10.712 -20.360 12.924 -20.542 13.863 -20.438 12.583 -5.385 -8.053 -5.543 -7.543 -5.697 -7.436 -0.772 18.789 -1.284 18.533 -1.010 18.089 5.290 26.308 5.875 26.038 5.853 26.326 222 ATOM 2803 0H2 H20 544 -13.634 -13.651 50.337 1.00 32.32 00 0 0* 0 0 0 00 *@0 0*0*.

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2804 2805 2806 2807 2808 2809 2810 2811 2812 2813 2814 2815 2816 2817 2818 2819 2820 2821 2822 2823 2824 2825 2826 2827 2328 2829 2830 2831 2832 2833 2834 2935 2836 2337 2S38 :339 2840 2841

HI

Hl H2

OH

Hl H2

OH.

Hl H2

OH:

Hi H2 OH2 Hi H12 0H2 Hl H2 0H2 Hl H2 0H2 Hi H2 0H2 Hl H2 0H2 Hi H2 0H2 Hl H2 DH2 Hl H2 H20 *H20 r2 H20 *H20 H2 0 2 H20 H2 0 H2 0 2 H20 H2 0 H2 0 2 H20 H20 H20 *H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 H20 544 544 545 545 545 546 546 546 547 547 547 549 549 549 550 550 550 551 551 551 552 552 552 553 553 553 554 554 554 555 555 555 556 556 556 557 557 557 -13.622 -14.594 -14.365 -13.576 6.675 4.419 7.290 4.690 6.944 3.519 -19.308 6.081 -19.538 6.138 -18.372 5.871 -0.121 9.589 0.690 10.066 -0.740 10.279 -21.186 -9.641 -21.706 -9.261 -20.925 -10.499 -19.368 -9.513 -19.314 -8.555 -18.853 -9.794 -29.465 1.964 -28.568 1.698 -29.959 1.156 -11.132 -14.092 -11.162 -13 .825 -10.792 -14.983 15.549 7.780 16.001 7.569 15.451 8.759 -6.955 -6.005 -6.261 -6.655 -6.769 -5.912 26.977 -3.406 26.901 -2.533 26.567 -3.960 28.411 -2.810 28.703 -3.042 27.572 -2.359 -3.769 0.192 -3.997 0.505 -4.594 0.325 50.588 49.736 46.648 47.341 46.428 75.052 74.117 75.036 22.739 22.559 23.010 52.393 51.676 52 .022 74.224 74.189 73.467 65.682 65 .445 65.517 61.004 60.080 60.930 43 .275 42.453 43.198 57.945 58.193 57.007 67.817 67 .411 67.122 64.708 65.597 64.889 55.470 54.588 55.939 1.0 1.0 1.0 1.0i 1.0 1.00 1 .00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1..00 0 30.02 0 0.00 0 0.00 0 51.03 00.00 0 0.00 39.87 0.00 0.00 33 .61 0.00 0.00 42.38 0.00 0 .00 30.82 0 .00 0.00 44.69 0.00 0.00 41.22 0.00 0.00 42 .99 0.00 0.00 32.14 0.00 0.00 30.05 0.00 0.00 36.92 0.00 0. 00 1.00 0.00 1.00 0.00 223 1 5 ATOM 2842 ATOM 2843 ATOM 2844 ATOM 2845 ATOM 2846 ATOM 2847 ATOM 2848 ATOM 2849 ATOM 2850 ATOM 2851 ATOM 2852 ATOM 2853 ATOM 2854 ATOM 2855 ATOM 2856 ATOM 2857 ATOM 2858 ATOM 2859 ATOM 2860 ATOM 2861 ATOM 2862 ATOM 2863 ATOM 2864 ATOM 2865 ATOM 2866 ATOM 2867 ATOM 2868 ATOM 2869 ATOM 2870 ATOM 2871 ATOM 2872 ATOM 2873 ATOM 2874 ATOM 2875 ATOM 27 ATOM 2877 ATOM 27 ATOM 2879 ATOM 2880 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 558 558 558 559 559 559 560 560 560 561 561 561 563 563 563 569 569 569 570 570 570 572 572 572 573 573 573 574 574 574 575 575 575 576 576 576 577 577 577 -18.369 11.227 -19.062 11.911 -18.590 10.704 -5.557 1.430 -6.379 0.902 -5.811 2.195 -1.244 -1.789 -1.114 -2.419 -0.486 -1.214 -13.464 -16.412 -13.891 -17.167 -12.907 -16.874 8.297 7.021 9.196 6.664 8.400 7.891 -18.672 9.411 -18.454 10.301 -19.299 9.181 -4.013 16.605 -3.642 15.998 -4.727 17.023 -6.268 16.662 -6.777 16.796 -5.615 17.379 -18.387 -26.644 -17.586 -26.570 -18.382 -27.600 -11.225 -10.882 -12.100 -10.489 -11.400 -11.765 -7.241 6.911 -6.378 7.294 -7.127 6.659 -2.732 3.489 -2.509 3.272 -3.201 4.317 -1.004 -5.395 -1.718 -5.183 -0.242 -5.437 49.122 49. 168 49.898 51. 259 51. 227 50. 750 50. 252 49. 540 50. 163 50.896 51. 314 50.251 48.013 48.079 48.412 70.985 70.720 70.297 50.811 51. 464 51.309 44. 180 45.000 44.261 47 .160 46.621 47.318 43.386 43.454 43.056 24.257 24. 478 23.334 69.646 68.740 69.547 42.848 42.244 42.261 1.00 40.83 1.00 0.00 1.00 0.00 1.00 37.40 1.00 0.00 1.00 0.00 1.00 42.03 1.00 0.00 1.00 0.00 1.00 40.41 1.00 0.00 1.00 0.00 1.00 45.26 1.00 0.00 1.00 0.00 1.00 42.69 1.00 0.00 1.00 0.00 1.00 50.36 1.00 0.00 1.00 0.00 1.00 24.25 1.00 0.00 1.00 0.00 1.00 49.62 1.00 0.00 1.00 0.00 1.00 28.82 1.00 0.00 1.00 0.00 1.00 46.54 1.00 0.00 1.00 0.00 1.00 35.00 1.00 0.00 1.00 0.00 1.00 31.83 1.00 0.00 1.00 0.00 224 ATOM 2881 OH2 H20 579 ATM 88 8282 592.618 6.038 53.054 1.00 53.16 .0.

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2882 2883 2884 2885 2886 2887 2888 2889 2890 2891 2892 2893 2894 2895 2896 2897 2898 2899 2900 2901 2902 2903 2904 2905 2906 2907 2908 2909 2910 2911 2912 2913 2914 2915 2916 2917 2918 2919 Hi H20 H2 H20 0H2 H20 Hi H20 H2 820 0H2 820 Hi H20 82 H20 0H2 H20 Hi H20 H2 H20 082 H20 Hi H20 H2 H20 0H2 820 H1 820 82 820 082 820 Hi H20 H2 H20 082 H20 Hi 820 82 820 0H2 820 Hl 820 82 820 082 820 Hl 820 82 820 082 820 Hl 820 82 820 082 820 H1 820 82 820 082 820 Hl 820 82 820 579 579 580 580 580 581 581 581 582 582 582 583 583 583 584 584 584 585 585 585 586 586 586 587 3-7 588 588 589 589 589 589 592 592 593 593 593 2.20E 3 53C -3 .109 -4.013 -3 .145 -15.517 -14.609 -15 .977 4.831 5.295 5.264 -7.370 -7.859 -8.070 11.021 11.035 11.358 -13.463 -13.880 -12.578 -21.459 -20.860 -21.155 9 .552 10 .017 8 .874 -18.589 -17.885 -18.406 11.877 12.160 12 .543 -26.188 -26. 971 -26.094 -12.898 -12.354 -13 .273 5.196 5.782 1.708 1.787 2.263 7.216 7.036 6.404 21.847 22.312 20.951 -2.505 -2.031 -2.637 8.553 9.388 8.841 4.859 5.285 5.274 -21.141 -20.849 -22.070 9.085 9.328 8.487 16.079 16.496 15.135 9.205 9.585 8.490 -5.587 -5.989 -4.777 10.911 10.108 10.940 53.266 52.875 61. 212 61.547 60.427 36. 498 36.239 36.259 47.571 46.821 47.474 28.449 27.773 29.095 47.239 47.727 46.355 41. 287 42.041 41. 218 46.452 47.150 46.366 29.404 28.595 29.061 53 .026 53.527 53 .154 44.689 43 .847 44.824 57.097 57.502 57.619 38.656 38.666 39.540 1.00 0.00 1.00 0.00 1.00 32.77 1.00 0.00 1.00 0.00 1.00 45.24 1.00 0.00 1.00 0.00 1.00 53.78 1.00 0.00 1.00 0.00 1.00 43.85 1.00 0.00 1.00 0.00 1.00 55.00 1.00 0.00 1.00 0.00 1.00 51.26 1.00 0.00 1.00 0.00 1.00 38.96 1.00 0.00 1.00 0.00 1.00 21.31 1.00 0.00 1.00 0.00 1.00 47.95 1.00 0.00 1.00 0.00 1.00 37.00 1.00 0.00 1.00 0.00 1.00 33.07 1.00 0.00 1.00 0.00 1.00 46.97 1.00 0.00 1.00 0.00 225 0 ATOM 2920 082 H20 594 ATOM 2921 Hl H-20 594 ATOM 2922 H2 H20 594 ATOM 2923 OH2 H2O 595 ATOM 2924 81l H-20 595 ATOM 2925 H2 H20 595 ATOM 2926 0H2 H20 596 ATOM 2927 H1 H20 596 ATOM 2928 82 H20 596 1 0 ATOM 2929 082 820 597 ATOM 2930 H1 H20 597 ATOM 2931 82 H-20 597 ATOM 2932 0H2 820 598 ATOM 2933 Hl 820 598 1 5 ATOM 2934 H2 820 598 ATOM 2935 082 820 599 ATOM 2936 H1 H20 599 ATOM 2937 H2 820 599 ATOM 2938 082 820 601 ATOM 2939 Hl 820 601 ATOM 2940 82 H20 601 ATOM 2941 082 820 602 ATOM 2942 Hl 820 602 ATOM 2943 H2 820 602 ATOM 2944 082 H20 603 ATOM 2945 H2. H20 603 ATOM 2946 H2 820 603 ATOM 2947 082 820 604 ATOM 2948 H1 820 604 ATOM 2949 82 820 604 ATOM 2950 082 820 605 ATOM 2951 8-1 820 605 ATOM 2952 82 820 605 ATOM 2953 082 820 606 ATOM 2954 81 820 606 ATOM 2955 82 820 606 ATOM 2956 082 820 608 ATOM 2957 8:1 820 608 ATOM 2958 82 820 608 -3.396 -3 .313 13 .656 14.189 14. 368 10.754 10. 942 11.653 8.570 8.461 7.661 15.043 14.279 15.457 -15.660 -16.222 -15.144 10.395 10.006 9 .821 -8.774 -8.038 -8.979 17.749 16.697 7.244 7.235 7.167 5.887 6.831 5.535 -1.874 -2 .699 -1.660 10.456 10.904 11.173 0.506 0.052 1.096 0.423 0.653 -0.291 4.671 4.434 3.782 48.079 1.00 0.00 49.134 1.00 0.00 45.221 1.00 39.29 44.397 1.00 0.00 45.864 1.00 0.00 46.780 1.00 58.01 46.995 1.00 0.00 46.772 1.00 0.00 32.277 1.00 42.55 31.792 1.00 0.00 32.512 1.00 0.00 42.923 1.00 62.88 43.307 1.00 0.00 42.429 1.00 0.00 40.466 1.00 47.74 39.836 1.00 0.00 39.903 1.00 0.00 33.259 1.00 37.60 34.105 1.00 0.00 32.928 1.00 0.00 74.569 1.00 26.62 75.158 1.00 0.00 74.258 1.00 0.00 62.725 1.00 37.86 62.099 1.00 0.00 62.806 1.00 0.00 39.570 1.00 34.28 40.517 1.00 0.00 39.318 1.00 0.00 60.745 1.00 36.79 60.798 1.00 0.00 60.001 1.00 0.00 36.092 1.00 21.56 35.650 1.00 0.00 36.233 1.00 0.00 57.878 1.00 65.19 57.744 1.00 0.00 58.606 1.00 0.00 -2.882 16.968 48.295 1.00 30.83 -17.104 -12.783 -16.954 -13.496 -16.217 -12.397 -18.900 -20.100 -18.978 -19.931 -19.834 -20.252 -5.985 -5.412 -5.650 -4.512 -6.609 -5.357 -7.708 -2.084 -6.902 -1.784 -8.190 -1.262 -3.614 10.212 -3.452 9.262 -3.027 10.425 226 ATOM 2959 0112 H20 609 -3.860 23.973 2981 .0 5.6 29.811 1.00 50.06

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 0 ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2960 2961 2962 2963 2964 2965 2966 2967 2968 2969 2970 2971 2972 2973 2974 2975 2976 2977 2978 2979 2980 2981 2982 2983 2984 2985 2986 2987 2988 2989 2990 2991 2992 2993 2994 2995 2996 2997 Hl1 H20 112 1120 0112 H20 Hl1 H20 112 H20 012 1120 Hl 1120 H2 H20 0H2 1120 Hi H20 112 H20 0H2 H120 Hl H120 H2 1120 0H2 1120 Hl 1120 H2 1120 0112 1120 Hi 1120 112 1120 0112 H20 Hl 1120 H2 1120 0112 1120 Hi 1120 H2 1120 0H2 1120 Hl 1120 112 1120 0112 1120 Hl 1120 112 1120 0112 1120 Hl 1120 112 1120 0112 1120 Hl 1120 112 1120 609 609 610 610 610 611 611 611 612 612 612 613 613 613 614 614 614 615 615 615 616 616 616 617 617 617 618 618 618 619 619 619 620 620 620 621 621 621 -15.333 -21. 240 -21. 322 -21. 978 -28.312 -27.631 -28.949 -12.785 -13 .581 -12.320 -26.951 -27.479 -27.225 0.669 1.054 -0.020 -29.510 -8.832 -9.290 -8.198 0.830 0.653 0.130 13.825 13.348 13.191 9.367 9.463 10.150 -5.217 -5.954 -5.664 -3.959 23.569 -4.765 24.102 -14.484 -29.114 -13.947 -29.402 28.947 30.103 38.149 38.898 38.352 55.096 54.233 55.041 71.261 70.617 71 .091 37.299 37.068 37.859 64.841 64.039 65.326 31.942 32.433 31.430 38.280 37.462 38.127 73.997 73.198 73 .936 64.699 65.388 64.106 53 .655 53.684 54.416 58.309 59.248 57 .952 53 .875 53.730 54.627 1.00 0.00 1.00 0.00 1.00 37.42 1.00 0.00 1.00 0.00 1.00 28.35 1.00 0.00 1.00 0.00 1.00 57.03 1.00 0.00 1.00 0.00 1.00 58.02 1.00 0.00 1.00 0.00 1.00 44.43 1.00 0.00 1.00 0.00 1.00 34.30 1.00 0.00 1.00 0.00 1.00 52.02 1.00 0.00 1.00 0.00 1.00 32 1.00 0.00 1.00 0.00 1.00 39.97 1.00 0.00 1.00 0.00 1.00 59.42 1.00 0.00 1.00 0.00 1.00 38 .58 1.00 0.00 1.00 0.00 1.00 52.25 1.00 0.00 1.00 0.00 -21.268 -20.889 -20.821 -20.660 -21.549 -12.839 -13.386 -12 .500 -16 .254 -16.278 -16.940 0.609 1.450 0.683 -4.989 -5.068 -4.822 -26.221 -25.549 -26.714 -21.801 10.577 10.619 *9.678 12.102 12.774 12.440 7.758 7.256 8.342 -8.010 -8.214 -8.893 -7.530 -8.202 -7.882 227 ATOM 2998 OH2 H20 622 -28.638 3.741 68.846 1.00 59.40 15 ATOM 2999 ATOM 3000 ATOM 3001 ATOM 3002 ATOM 3003 ATOM 3004 ATOM 3005 ATOM 3006 ATOM 3007 ATOM 3008 ATOM 3009 ATOM 3010 ATOM 3011 ATOM 3012 ATOM 3013 ATOM 3014 ATOM 3015 H1 H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 622 622 623 623 623 624 624 624 625 625 625 626 626 626 627 627 627 -28.605 3.555 69.794 -28.709 2.848 68.480 -2.090 21.292 26.341 -1.329 21.457 26.918 -1.757 21.533 25.471 2.746 10.956 28.128 2.977 11.822 27.786 1.817 10.899 27.885 -21.125 -12.685 57.962 -22.032 -12.954 57.802 -21.176 -11.723 57.883 -3.498 0.232 28.222 -3.396 -0.544 28.792 -4.076 -0.127 27.533 -6.243 -1.618 39.632 -6.546 -0.718 39.813 -6.989 -2.019 39.186 1.00 0.00 1.00 0.00 1.00 57.48 1.00 0.00 1.00 0.00 1.00 62.18 1.00 0.00 1.00 0.00 1.00 56.36 1.00 0.00 1.00 0.00 1.00 45.90 1.00 0.00 1.00 0.00 1.00 33.00 1.00 0.00 1.00 0.00

END

*Note: See copyright notice on page 1.

228 Appendix III: Coordinates for the 3D structure of ZAP-NC:zl "dimer- structure (two moleucles of complex per unit cell)* REMARK FILENAME= "tzape- ze tal -reb7 -wat-s low. pdb" REMARK TOPH19.pep -MACRO for protein sequence created by user: marcos

C

*5

S

S

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

CB ASP CG ASP ODi ASP 0D2 ASP C ASP 0 ASP HTI ASP HT2 ASP N ASP HT3 ASP CA ASP N PRO CD PRO CA PRO CB PRO CG PRO C PRO 0 PRO N ALA 3.023 3.616 3.875 3.795 3.125 1.915 1.919 3.317 2.872 2.808 3.564 3.958 5.405 3.556 4.853 5.881 2.524 1.665 2.568 3.317 1.662 2.291 0.348 -0.543 0.126 0.778 -1.089 -1.098 -2.394 -3.390 -2.376 -1.541 -3.462 -2.223 -2.263 -1.198 -2.930 -2 .908 -4.746 -5.471 -5.087 -5.797 -3 .885 -2 .177 -2.209 -1.192 -0.568 -1.611 -0.151 0.351 0.146 -0.168 1.120 1.818 0.580 1.361 -0.726 -1.310 -1.294 -2.784 -0 .721 -0.608 -0.363 -0.482 13.100 12 .417 11. 212 13 .066 15 .585 15.816 15 .191 15 .778 14.923 14.172 14.482 16.299 16.150 17.314 17.733 17.455 16.856 17 .601 15.556 15.008 14.996 13 .819 14.532 14.246 14.574 15.006 14.028 14.300 14.540 13. 844 15. 806 16.284 1.00 13.09 1.00 20.07 1.00 23.94 1.00 20.96 1.00 11.37 1.00 14.62 1.00 0.00 1.00 0.00 1.00 17.39 1.00 0.00 1.00 13.78 1.00 6.97 1.00 10.48 1.00 10.28 1.00 9.59 1.00 10.34 1.00 12.09 1.00 15.40 1.00 14.44 1.00 0.00 1.00 11.85 1.00 11.48 1.00 12.81 1.00 14.41 1.00 10.58 1.00 0.00 1.00 14.14 1.00 16.49 1.00 16.09 1.00 21.55 1.00 17.76 1.00 0.00

ALA

ALA

ALA

ALA

ALA

ALA

ALA

ALA

ALA

ALA

ALA

HIS

HIS

229

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

NE2 HE2

C

O

N

H

CA

CB

CG

CD1 CD2

C

O

N

CD

CA

CB

CG

C

O

N

H

CA

CB

CG

CD1 CD2 CE1 CE2

CZ

C

O

HIS 7 HIS 7 HIS 7 HIS 7 LEU 8 LEU 8 LEU 8 LEU 8 LEU 8 LEU 8 LEU 8 LEU 8 LEU 8 PRO 9 PRO 9 PRO 9 PRO 9 PRO 9 PRO 9 PRO 9 PHE 10 PHE 10 PHE 10 PHE 10 PHE 10 PHE 10 PHE 10 PHE 10 PHE 10 PHE 10 PHE 10 PHE 10 CA HIS CB HIS CG HIS CD2 HIS ND1 HIS HD1 HIS CE1 HIS -3.533 -3.352 -2.219 -2.489 -0.885 -0.298 -0.376 -1.347 -1.204 -3.741 -4.720 -2.817 -2.221 -2.871 -1.436 -0.575 -1.174 0.801 -3.808 -3.580 -4.863 -5.197 -5.849 -6.966 -6.309 -5.355 -6.026 -4.162 -3.692 -3.498 -3.024 -2.321 -0.943 -3.058 -0.301 -2.417 -1.047 -2.294 -1.349 0.171 -0.066 0.769 1.750 0.783 0.154 1.717 2.282 2.905 1.658 2.243 2.341 1.861 3.783 4.278 4.915 4.730 4.382 4.079 3.600 4.873 5.551 5.081 5.752 6.490 5.835 5.867 6.430 6.342 7.181 8.538 8.453 8.232 8.624 8.182 8.580 8.362 6.405 7.007 16.488 18.009 18.644 19.576 18.461 17.994 19.227 19.884 20.638 16.209 16.644 15.557 14.946 15.423 15.161 16.234 17.610 16.098 14.265 13.154 14.434 15.693 13.389 14.144 15.289 12.149 11.110 12.259 13.107 11.203 11.737 13.094 13.179 14.267 14.416 15.500 15.583 10.696 10.175 1.00 16.60 1.00 22.31 1.00 27.59 1.00 28.93 1.00 25.24 1.00 0.00 1.00 28.14 1.00 26.99 1.00 0.00 1.00 13.37 1.00 14.49 1.00 10.78 1.00 0.00 1.00 7.84 1.00 6.56 1.00 3.50 1.00 6.85 1.00 2.00 1.00 8.93 1.00 10.23 1.00 9.86 1.00 9.32 1.00 8.41 1.00 10.72 1.00 11.80 1.00 12.47 1.00 18.23 1.00 9.59 1.00 0.00 1.00 7.32 1.00 4.10 1.00 4.21 1.00 4.43 1.00 2.00 1.00 2.00 1.00 2.51 1.00 2.00 1.00 7.70 1.00 7.52 230 ATOM 72 N PHE 11 -2.224 5.088 10.921 1.00 6.80 ATOM 73 H PEE 11 -2.965 4.597 11.332 1.00 0.00 ATOM 74 CA PEE 11 -1.120 4.299 10.415 1.00 7.59 ATOM 75 CB PEE 11 -0.705 3.238 11.425 1.00 5.71 ATOM 76 CG PEE 11 0.248 2.165 10.884 1.00 7.61 ATOM 77 CD1 PHE 11 1.519 2.510 10.393 1.00 2.06 ATOM 78 CD2 PHE 11 -0.165 0.821 10.874 1.00 2.94 ATOM 79 CEl PEE 11 2.370 1.522 9.895 1.00 2.00 ATOM 80 CE2 PEE 11 0.700 -0.160 10.373 1.00 3.03 ATOM 81 CZ PEE 11 1.962 0.191 9.888 1.00 4.25 ATOM 82 C PHE 11 -1.686 3.663 9.154 1.00 7.98 ATOM 83 0 PEE 11 -2.784 3.126 9.188 1.00 9 .38 ATOM 84 N TYR 12 -1.000 3.774 8.025 1.00 4.03 *ATOM 85 H TYR 12 -0.170 4.294 8.022 1.00 0.00 ATOM 86 CA TYR 12 -1.522 3.259 6.774 1.00 7.69 ATOM 87 CB TYR 12 -1.455 4.329 5.714 1.00 4.20 ATOM 88 CG TYR 12 -2.582 5.340 5.795 1.00 3.37 ATOM 89 CD1 TYR 12 -2.543 6.332 6.766 1.00 2.00 ATOM 90 CEl TYR 12 -3.532 7.297 6.818 1.00 2.00 20 ATOM 91 CD2 TYPR 12 -3 .617 5.301 4.872 1.00 2.00 ATOM 92 CE2 TYR 12 -4.609 6.269 4.918 1.00 3.76 ATOM 93 CZ TYR 12 -4.557 7.263 5.891 1.00 5.13 *ATOM 94 OH TYR 12 -5.521 8.242 5.911 1.00 6.92 ATOM 95 HE TYR 12 -5.379 8.771 6.713 1.00 0.00 ATOM 96 C TYPR 12 -0.793 2.041 6.249 1.00 10.10 *ATOM 97 0 TYR 12 -1.154 1.494 5.206 1.00 10.16 *ATOM 98 N GLY 13 0.290 1.623 6.899 1.00 4.96 ATOM 99 H GLY 13 0.676 2.192 7.592 1.00 0.00 ATOM 100 CA GLY 13 0.993 0.444 6.465 1.00 5.01 ATOM 101 C GLY 13 1.962 0.782 5.361 1.00 9.03 ATOM 102 0 GLY 13 2.466 1.911 5.324 1.00 9.88 ATOM 103 N SEP. 14 2.248 -0.181 4.484 1.00 6.75 ATOM 104 H SER 14 1.835 -1.069 4.566 1.00 0.00 ATOM 105 CA SEP. 14 3.216 -0.042 3.425 1.00 6 .38 ATOM 106 CB SER 14 3.761 -1.433 3 .160 1.00 12.45 ATOM 107 OG SER 14 4.042 -2.137 4.368 1.00 14.84 ATOM 108 HG SER 14 4.988 -2.032 4.504 1.00 0.00 ATOM 109 C SEP. 14 2.646 0.592 2 .163 1.00 9.03 ATOM 110 0 SER 14 2.597 -0.003 1.083 1.00 6.91 231

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

111 N ILE 112 H ILE 113 CA ILE 114 CB ILE 115 CG2 ILE 116 CG1 ILE 117 CD ILE 118 C ILE 119 0 ILE 120 N SER 121 H SER 122 CA SER 123 CB SER 124 OG SER 125 HG SER -26 C SER 127 0 SER 128 N ARG 129 H ARG 130 CA ARG 131 CB ARG 132 CG ARG 133 CD ARG 134 NE ARG 135 HE ARG 136 CZ ARG 137 NH1 ARG 138 HH11 ARG 139 HH12 ARG 140 NH2 ARG 141 HH21 ARG 142 HH22 ARG 143 C ARG 144 0 ARG 145 N ALA 146 H ALA -47 CA ALA 148 CB ALA -49 C ALA 2.120 2.188 1.610 0.538 -0.680 1.075 0.057 2.798 3.861 2.707 1.875 3.788 3.704 2.388 2.047 3.687 2.675 4.699 5.537 4.648 5.924 5.862 7.154 8.227 8.208 9.140 9.090 8.351 9.767 10.160 10.267 10.826 3 .467 2.767 3 .226 3.866 2.127 2 .157 0.752 1.812 2.238 2.588 3.627 2.860 4. 612 5.720 3.326 3.382 3.871 3.823 4.641 4.505 4.754 3.891 6.106 6.502 6.935 6.524 8.381 9.017 10.510 11.123 10.897 10.065 11.829 13.040 13.280 13.730 11.543 10.623 12.246 9 .007 9.855 8.597 7.978 9 .126 8 .565 8.856 2.312 3 .193 1.187 1.605 2.116 2.629 2.801 0.597 1.221 -0.603 -1.116 -1.154 -2.673 -3.152 -3.426 -0.714 -0.132 -0.968 -1.277 -0.757 -1.273 -1.338 -1.775 -0.825 -0.338 -0.522 -1.078 -1.704 -0.827 0.279 0.648 0.515 -1.478 -0.912 -2.725 -3.146 -3.517 -4.946 -2.957 1.00 12.05 1.00 0.00 1.00 4.84 1.00 6.22 1.00 2.00 1.00 4.45 1.00 2.00 1.00 4.88 1.00 9.72 1.00 2.18 1.00 0.00 1.00 2.42 1.00 8.87 1.00 3.44 1.00 0.00 1.00 2.00 1.00 2.00 1.00 2.93 1.00 0.00 1.00 7.56 1.00 6.05 1.00 5.21 1.00 3.35 1.00 4.91 1.00 0.00 1.00 4.06 1.00 11.79 1.00 0.00 1.00 0.00 1.00 2.00 1.00 0.00 1.00 0.00 1.00 9.96 1.00 18 .22 1.00 8.79 1.00 0.00 1.00 6.30 1.00 6.16 1.00 6.92 232

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 0 ALA N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU O GLU N ALA H ALA CA ALA CB ALA C ALA

ALA

N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU o GLU N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU o GLU N HIS H HIS -0.107 0.506 1.209 -0.782 -0.933 -2 .377 -2.645 -3.479 -2 .030 919 -2.017 0.158 0.966 0.211 1. 649 -0.241 -1.206 0.379 1.116 0.040 1. 020 2.397 3 .519 4.557 3.407 -1.380 -2 .019 -1.962 -1.426 -3.372 -3.832 -3 .392 -3.683 -4.835 -2.752 -4 .273 -5.253 -3.959 -3.140 9 .754 7 .652 6.967 7.381 5.916 5.601 4.173 3 .996 3.243 8 .177 8.678 8.264 7 .756 9.052 9.038 10.487 10.973 11.097 10.617 12.416 12 .792 13 .047 13 .499 13 .853 13 .490 12 .520 13.528 11.533 10.751 11.572 10.346 10.345 11.637 11.930 12.353 11.631 12.378 10.856 10.318 -2.973 -2.443 -2.446 -1 .814 -1.471 -1.128 -0.680 0.201 -1.201 -0.532 -0.270 0.270 0 .027 1.508 2 .045 1.209 1.808 0.190 -0.239 -0.312 -1.412 -0.773 -1.669 -1 .142 -2 .883 -0.818 -0.527 -1.497 -1.745 -1.859 -2.661 -4.114 -4.867 -5.138 -5.183 -0.641 -0.613 0.392 0.345 1.00 7.53 1.00 7.90 1.00 0.00 1.00 9.39 1.00 10.49 1.00 19.14 1.00 20.65 1.00 17.14 1.00 24.68 1.00 3.96 1.00 8.60 1.00 7.91 1.00 0.00 1.00 5.76 1.00 2.00 1.00 4.60 1.00 5.16 1.00 4.13 1.00 0.00 1.00 2.10 1.00 4.68 1.00 2.00 1.00 2.00 1.00 5.32 1.00 13 .97 1.00 6.29 1.00 10.48 1.00 8.02 1.00 0.00 1.00 7.52 1.00 7.05 1.00 14.40 1.00 8.48 1.00 9.34 1.00 11.08 1.00 6.86 1.00 5.32 1.00 5.94 1.00 0.00 233

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212 213 2 14 Z15 216 217 218 219 220 221 222 223 224 225 226 227 CA HIS CB HIS CG HIS CD2 HIS ND1 HIS HD1 HIS CEl HIS NE2 HIS HE2 HIS C HIS 0 HIS N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LZtJ 0 LEU N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS 0 LYS N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU -4 .755 -4.321 -4-867 -6 .203 -4.188 -3-210 -5 .036 -6-245 -7-054 635 -5.626 -3 .421 -2 .646 -3.206 -1.701 823 -1 .454 0.498 -3-.973 652 -4-.000 -3 .462 -4.774 -4-.496 -3 153 -2.581 -3 .260 -2 .559 -3 .027 -1.570 -2-588 -6 .265 -6.897 -6.838 -6 .273 -8.251 -8.620 -8.869 -8.667 10.908 9.773 8 .436 8.130 7 .361 7.263 6 .418 6 .892 6.418 12.252 12 .842 12.790 12.264 14.085 14.303 14.200 13.379 13 .624 15.138 15.982 15.036 14.341 15.932 15.670 16.255 15.554 15.890 15.231 14.321 15.066 15 .821 15.828 16.878 14.617 13.839 14. 406 12.933 12.403 10.906 1 .612 2 .499 2.044 1.947 1. 687 1.722 1.389 1.547 1.246 2.349 2.795 2.458 2 .177 3 .063 3.096 4.370 5.465 3 .967 2.252 2.852 0.904 0.474 0. 043 -1.428 .839 -3 .051 -4.355 -5.444 -5.634 169 -6.298 0.258 0.404 0.301 0.106 0.623 0.400 -1.006 -1 .070 i. 00 1.00 1.00 1.00 1.00 1 00 1.00 1.00 1.00 1.00 4.09 1.00 6.37 1.00 3.53 1.00 0.00 1.00 5 .01 1.00 2.00 1.00 6.54 1.00 7.05 1.00 2.00 1.00 11.01 1.00 10.63 1.00 12.49 1.00 0.00 1.00 7.14 1.00 8.00 1.00 5.27 1.00 3 1.00 10.38 1.00 11.78 1.00 0.00 1.00 0.00 1.00 0.00 1.00 10.22 1.00 9.54 1.00 11.16 1.00 0.00 1.00 9.37 1.00 11.52 1.00 15.81 1.00 12.44 5 .56 2 .00 2.00 2 .00 3 .99 0 .00 4.29 2 .00 0.00 -234 ATOM 228 CD2 LEU 26 -10.274 12.781 -1.405 1.00 14.24 0.

00.

0 00

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

-3 5 ATOM

ATOM

ATOM

ATOM

ATOM

229 c LEU 230 o LEU 231 N ALA 232 H ALA 233 CA ALA 234 CB ALA 235 C ALA 236 0 ALA 237 N GLY 238 H GLY 239 CA GLY 240 C GLY 241 0 GLY 242 N MET 243 H MET 244 CA MET 245 CB MET 246 CG MET 247 SD MET 248 CE MET 249 C MET 250 0 MET 251 N ALA 252 H ALA 253 CA ALA 254 CB ALA 255 c ALA 256 0 ALA 257 N ASP 258 H ASP 259 CA ASP 260 CB ASP 261 CG ASP 262 0D1l ASP ,93 OD2 ASP 264 C ASP 2E5 0 ASP 2766 N GLY 26 26 27 27 27 27 27 27 28 28 28 28 28 29 29 29 29 29 29 29 29 29 30 30 30 30 30 30 31 31 31 31 31 31 31 31 31 32 -8.631 -9.801 -7.692 -6.777 -7.994 -7.036 -7.953 -8.111 -7.739 -7.484 -7.896 -6.628 -6.690 -5.473 -5.490 -4.190 -3 .995 -3.777 -2.291 -1.010 -3.856 -2.966 -4.500 -5.182 -4.164 -5.179 -2.775 -2.295 -2.076 -2.486 -0 .776 -0.288 0.098 0.146 0.365 -0.900 -1.895 0.048 14.799 15.111 14 .822 14.533 15.224 14.511 16.734 17.181 17.589 17.253 19.028 19.840 21.035 19.214 18.237 19.893 20.563 19 .617 18.598 19.682 20.922 21.768 20.905 20.223 21.845 21.738 21.578 20.435 22 .614 23 .499 22 .454 23.751 24.844 25.992 24.563 21.447 21.484 20.550 2 .069 2.355 3 .024 2 .808 4.386 5.304 4.652 5.782 3 .664 2.781 3 .827 3 .923 4.200 3 .803 3 .712 3 .778 2.387 1.225 1.382 0.859 4 .854 4.665 6.021 6.167 7.095 8.228 7 .669 7.630 8.163 8.124 8.823 9.448 8 .474 8.888 7.309 9.952 10.668 10 .124 1.00 10.95 1.00 14.32 1.00 11.08 1.00 0.00 1.00 11.08 1.00 10.64 1.00 7.17 1.00 11.67 1.00 12.48 1.00 0.00 1.00 7.75 1.00 4.07 1.00 6.51 1.00 2.00 1.00 0.00 1.00 8.42 1.00 10.20 1.00 2.00 1.00 8.85 1.00 2.00 1.00 10.87 1.00 10.88 1.00 11.57 1.00 0.00 1.00 10.40 1.00 6.30 1.00 10.33 1.00 13.22 1.00 12.01 1.00 0.00 1.00 12.46 1.00 13.37 1.00 21.50 1.00 24.55 1.00 20.09 1.00 7.22 1.00 4.46 1.00 10.27 235 ATOM 267 H GLY 32 0.798 20.509 9.504 1.00 0.00 a 9 ATOM 268 ATOM 269 ATOM 270 ATOM 271 ATOM 272 ATOM 273 ATOM 274 ATOM 275 ATOM 276 ATOM 277 ATOM 278 ATOM 279 ATOM 280 1 5 ATOM 281 ATOM 282 ATOM 283 ATOM 284 ATOM 285 20 ATOM 286 ATOM 287 ATOM 288 ATOM 289 ATOM 290 ATOM 291 ATOM 292 ATOM 293 ATOM 294 ATOM 295 ATOM 296 ATOM 297 ATOM 298 ATOM 299 ATOM 300 ATOM 301 ATOM 302 ATOM 303 ATOM 304 ATOM 305 CA GLY C GLY O GLY N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N PHE H PHE CA PHE CB PHE CG PHE CD1 PHE CD2 PHE CEI PHE CE2 PHE CZ PHE C PHE o PHE N LEU H LEU CA LEU CE LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N LEU H LEU -0.033 -0.823 -0.854 -1.475 -1.447 -2.163 -2.958 -3.782 -5.026 -4.230 -1.040 -0.088 -1.096 -1.873 -0.031 0.906 0.293 0.609 -0.598 0.036 -1.171 -0.851 -0.567 -1.726 0.268 1.189 -0.072 -0.724 -0.088 0.959 -1.244 1.245 2.324 1.191 0.323 2.380 2.363 3.640 19.590 18.338 17.457 18.224 18.977 17.020 17.285 16.168 15.832 16.632 16.019 16.324 14.827 14.606 13.841 13.955 13.474 12.195 14.301 11.755 13.850 12.578 12.412 12 .147 11.458 11.706 10.050 9.614 9 .773 8.732 9 .677 9.317 9.933 8 .005 7.551 7.184 6.596 6.400 11.205 10.859 11.714 9.681 9.055 9.241 7.952 7.277 8.081 5.924 8.975 8.255 9.559 10.113 9.449 10.668 12.001 12.511 12.705 13.703 13.902 14.396 9.374 9.661 9.034 8.790 9.046 7.712 6.319 5.950 5.386 9.250 9.225 9.422 9.390 9.594 10.986 11.741 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 i.00 1.00 1.00 1.00 1.00 1.00 00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 i.00 1.00 1 0 .00 1. 00 1.00 1.00 1.00 1.00 i. 00 1.00 00 1.00 1.00 1.00 8.51 7.26 8.25 11.32 0.00 7.48 6.35 6.57 2.00 2.00 6.22 6.43 8.18 0.00 6.96 9.24 11.41 10.54 6.42 2.02 7.27 6.84 5.22 3.39 5.72 0.00 4.60 8 .73 3 2.00 2 .00 3 .92 2 .00 5.92 0.00 8.39 11.32 14.05 236 ATOM 306 CD1 LEU 36 4.436 7.705 11.802 1.00 16.00 15 20 ATOM 307 ATOM 308 ATOM 309 ATOM 310 ATOM 311 ATOM 312 ATOM 313 ATOM 314 ATOM 315 ATOM 316 ATOM 317 ATOM 318 ATOM 319 ATOM 320 ATOM 321 ATOM 322 ATOM 323 ATOM 324 ATOM 325 ATOM 326 ATOM 327 ATOM 328 ATOM 329 ATOM 330 ATOM 331 ATOM 332 ATOM 333 ATOM 334 ATOM 335 ATOM 336 ATOM 337 ATOM 338 ATOM 339 ATOM 340 ATOM 341 ATOM 342 ATOM 343 ATOM 344 CD2 LEU NE ARG HE ARG CZ ARG NH1 ARG HH11 ARG HH12 ARG NH2 ARG HH21 ARG HH22 ARG C ARG O ARG N GLN H GLN CA GLN CB GLN CG GLN

LEU

LEU

ARG

ARG

ARG

ARG

ARG

ARG

3.265 2.337 1.281 3.451 4.319 3.436 3.347 4.431 4.133 4.999 4.751 6.090 6.467 5.927 7.293 6.826 6.527 7.645 4.742 5.673 4.774 4.022 5.938 5.595 6.806 6.483 6.523 6.109 6.074 5.914 6.999 6.685 8.249 8.430 9.348 10.486 11.920 9.677 5.884 6.074 5.554 5.641 6.012 4.601 5.207 6.217 6.877 7.996 8.885 7.884 6.714 5.895 6.655 8.967 9.860 8.898 3.896 4.451 2.634 2.306 1.799 0.351 -0.558 -2.001 -2.458 -2.747 -2.344 -3.686 2.228 2.463 2.259 1.978 2.636 3.061 3.657 1.390 13.125 8.546 8.193 8.002 8.281 7.001 5.570 5.175 3.834 3.521 3.842 2.784 2.287 2.467 1.729 2.509 2.843 1.946 7.236 7.813 6.860 6.330 7.031 6.761 6.935 6.637 5.497 7.656 8.548 7.478 6.044 4.877 6.487 7.409 5.640 6.507 5.614 4.861 1.00 9.12 1.00 7.14 1.00 5.23 1.00 7.21 1.00 0.00 1.00 6.63 1.00 6.99 1.00 7.51 1.00 3.14 1.00 2.00 1.00 0.00 1.00 2.00 1.00 9.05 1.00 0.00 1.00 0.00 1.00 2.00 1.00 0.00 1.00 0.00 1.00 4.63 1.00 6.35 1.00 5.04 1.00 0.00 1.00 7.58 1.00 7.74 1.00 13.64 1.00 14.53 1.00 12.05 1.00 18.12 1.00 0.00 1.00 0.00 1.00 10.26 1.00 17.97 1.00 5.47 1.00 0.00 1.00 5.68 1.00 2.00 1.00 7.85 1.00 8.60

CD

OE1 NE2 HE21 HE22

C

GLN

GLN

GLN

GLN

GLN

GLN

O GLN N CYS H CYS CA CYS CB CYS SG CYS C CYS 237

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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345 0 CYS 346 N LEU 347 H LEU 348 CA LEU 349 CE LEU 350 CG LEU 351 CD1 LEU 352 CD2 LEU 353 C LEU 354 0 LEU 355 N ARG 356 H ARG 357 CA ARG 358 CB ARG 359 CG ARG 360 CD ARG 361 NE ARG 362 HE ARG 363 CZ ARG 364 NHI ARG 365 HH11 ARG 366 HH12 ARG 367 NH2 ARG 368 HH21 ARG 369 HH22 ARG 370 C ARG 371 0 ARG 372 N SER 373 H SER 374 CA SER 375 CB SER 376 OG SER 377 HG SER 378 C SER 379 0 SER 380 N LEU 381 H LEU 382 CA LEU 383 CE LEU 9.841 0.306 5.419 1.00 7.46 9.732 1.534 3.551 1.00 9.77 9.503 2.417 3.173 1.00 0.00 10.016 0.439 2.642 1.00 8.59 9.288 0.734 1.312 1.00 6.71 7.773 1.006 1.449 1.00 11.30 7.122 1.289 0.101 1.00 8.08 7.140 -0.199 2.108 1.00 11.61 11.509 0.271 2.441 1.00 5.73 11.937 -0.688 1.800 1.00 9.26 12.309 1.209 2.962 1.00 8.34 11.897 1.977 3.405 1.00 0.00 13.763 1.249 2.813 1.00 2.90 14.210 2.666 2.555 1.00 2.00 13.454 3.361 1.465 1.00 2.98 13.444 4.854 1.636 1.00 2.00 14.799 5.288 1.685 1.00 8.56 15.451 4.892 1.068 1.00 0.00 15.236 6.186 2.575 1.00 12.54 14.464 6.783 3.503 1.00 5.62 13.491 6.577 3.561 1.00 0.00 14.875 7.443 4.131 1.00 0.00 16.541 6.418 2.555 1.00 9.56 17.122 5.945 1.892 1.00 0.00 16.939 7.080 3.189 1.00 0.00 14.546 0.749 4.026 1.00 3.10 15.738 0.442 3 .924 1.00 6.59 13.886 0.603 5.172 1.00 6.64 12.914 0.695 5.186 1.00 0.00 14.523 0.260 6.436 1.00 10.06 14.450 1.447 7.379 1.00 7.22 15.317 2.451 6.893 1.00 18.52 15.130 3.248 7.414 1.00 0.00 13.877 -0.927 7.130 1.00 13.90 12.722 -1.258 6.862 1.00 18.52 14.615 -1.614 7.985 1.00 14.21 15.551 -1.367 8.099 1.00 0.00 14.096 -2.659 8.842 1.00 12.11 15.245 -3.504 9.359 1.00 12.29

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384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 CG LEU CD1 LEU CD2 LEU C LEU 0 LEU N GLY H GLY CA GLY C GLY 0 GLY N GLY H GLY CA GLY C GLY O GLY N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CEl TYR CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR C TYR O TYR N VAL H VAL CA VAL CB VAL CG1 VAL CG2 VAL C VAL O VAL N LEU H LEU 15 .525 14.425 16.915 13 .405 14.057 12.099 11.625 11.327 11.099 10.677 11.279 11.397 11.122 9.769 8.978 9.511 10 .194 8.295 7.347 6 .921 5 .812 5 .463 7.684 7.343 6.233 5.905 6.725 8.678 9.856 7.691 6 .772 7.906 7 .904 8.233 8.969.

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462 HD1 HIS 463 CEl HIS 464 NE2 HIS 465 HE2 HIS 466 C HIS 467 0 HIS 468 N ASP 469 H ASP 470 CA ASP 471 CB ASP 472 CG ASP 473 ODi ASP 474 0D2 ASP 475 C ASP 476 0 ASP 477 N VAL 478 H VAL 479 CA VAL 480 CB VAL 481 CG1 VAL 482 CG2 VAL 483 C VAL 484 0 VAL 485 N ARG 486 H ARG 487 CA ARC 488 CB ARC 489 CG ARG 490 CD ARC 491 NE ARG 492 HE ARG 493 CZ ARC 494 NH1 ARG 495 HH11 ARG 496 HH12 ARG 497 NH2 ARG 498 HH21 ARC 499 HH22 ARG 4.076 5.135 5.832 3.011 3.752 2.344 1.756 2.319 3.692 3.782 4.872 2.790 1.944 2.571 0.844 0.390 0.204 627 -1.678 -1.419 1.224 1.087 2.250 2.287 3 .322 4 .611 4.532 5.795 5.926 6.452 5.350 4.586 4.408 4.189 5.584 6.170 5.161 3.524 25.555 25.652 26.325 23.224 22.848 24.398 24.593 25.378 26. 074 27.331 27.597 28.048 24 .749 24.963 23 .980 23 .945 23.208 24.166 23.357 25.201 22.395 22 .119 21.903 22 .011 21.141 21.966 23 .059 23 .872 24.706 24.356 25.913 26.464 25.984 27.367 26.607 26.232 27 .505 19 .911 8 .929 8.189 8.378 5 .233 4 .326 5.203 5.946 4.128 4 .077 3.203 2. 695 3.030 2.783 1 .752 2.869 3 .737 1 .800 0. 849 0.060 1.664 1.006 -0.185 1 .704 2 .677 1 .094 1.055 0 .020 0.061 -1.136 -1.888 -1.280 -0.336 0.524 -0.490 -2.390 -3.108 -2.516 1.961 1.00 2.82 1.00 2.00 1.00 0.00 1.00 6.14 1.00 7.03 1.00 7.04 1.00 0.00 1.00 7.2.9 1.00 13.83 1.00 19.58 1.00 24.03 1.00 20.95 1.00 7.16 1.00 4.53 1.00 8.53 1.00 0.00 1.00 8.93 1.00 12.04 1.00 7.47 1.00 8.15 1.00 9.82 1.00 9.21 1.00 8.33 1.00 0.00 1.00 9 .23 1.00 6.97 1.00 10.44 1.00 12.13 1.00 18.61 1.00 0.00 1.00 15.59 1.00 10.00 1.00 0.00 1.00 0.00 1.00 14.76 1.00 0.00 1.00 0.00 1.00 9 .89 2.809 24.027 9.315 1.00 0.00 ATOM 500 C ARC 241 ATOM 501 O ARG 55 3.145 19.914 ATOM 502 N PHE 56 4.170 18.888 ATOM 503 H PHE 56 4.544 18.997 ATOM 504 CA PHE 56 4.340 17.617 ATOM 505 CB PHE 56 4.098 16.469 ATOM 506 CG PHE 56 2.742 16.558 ATOM 507 CD1 PHE 56 2.644 16.978 ATOM 508 CD2 PHE 56 1.625 16.180 ATOM 509 CE1 PHE 56 1.397 17.010 ATOM 510 CE2 PHE 56 0.387 16.217 ATOM 511 CZ PHE 56 -0.271 16.629 ATOM 512 C PHE 56 5.720 17.453 ATOM 513 O PHE 56 6.669 17.846 ATOM 514 N HIS 57 5.911 16.893 15 ATOM 515 H HIS 57 5.145 16.575 ATOM 516 CA HIS 57 7.243 16.753 ATOM 517 CB HIS 57 7.410 17.781 ATOM 518 CG HIS 57 7.101 19.214 ATOM 519 CD2 HIS 57 5.851 19.759 ATOM 520 ND1 HIS 57 7.905 20.137 ATOM 521 HD1 HIS 57 8.788 19.977 ATOM 522 CE1 HIS 57 7.208 21.202 ATOM 523 NE2 HIS 57 5.978 20.952 ATOM 524 HE2 HIS 57 5.233 21.552 ATOM 525 C HIS 57 7.295 15.330 ATOM 526 0 HIS 57 6.364 14.882 ATOM 527 N HIS 58 8.296 14.567 ATOM 528 H HIS 58 9.012 14.961 ATOM 529 CA HIS 58 8.411 13.173 ATOM 530 CB HIS 58 8.491 12.344 ATOM 531 CG HIS 58 7.195 12.474 ATOM 532 CD2 HIS 58 7.013 13.360 ATOM 533 ND1 HIS 58 6.051 11.828 ATOM 534 HD1 HIS 58 5.844 11.123 ATOM 535 CE1 HIS 58 5.196 12.273 ATOM 536 NE2 HIS 58 5.794 13.197 ATOM 537 HE2 HIS 58 5.390 13.727 ATOM 538 C HIS 58 9.639 12.966 ATOM 539 O HIS 58 10.756 13.187 3.136 1.414 0.510 2.096 1.151 0.505 -0.820 1.224 -1.440 0.593 -0.735 2.654 1.989 3.847 4.376 4.422 5.554 5.116 5.157 4.602 4.213 4.328 4.666 4.438 4.945 5.611 4.535 3.981 4.887 3.620 2.834 1.813 2.960 3.619 2.087 1.403 0.691 5.731 5.271 1.00 7.57 1.00 11.16 1.00 0.00 1.00 10.07 1.00 10.65 1.00 5.39 1.00 7.49 1.00 2.00 1.00 2.00 1.00 4.37 1.00 3.23 1.00 7.33 1.00 3.76 1.00 7.78 1.00 0.00 1.00 9.13 1.00 9.13 1.00 5.87 1.00 4.86 1.00 5.61 1.00 0.00 1.00 2.00 1.00 8.92 1.00 0.00 1.00 7.66 1.00 11.39 1.00 9.95 1.00 0.00 1.00 7.60 1.00 3.50 1.00 2.00 1.00 2.00 1.00 4.99 1.00 0.00 1.00 2.00 1.00 2.00 1.00 0.00 1.00 7.66 1.00 6.10 242

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540 N PHE 541 H PHE 542 CA PHE 543 CB PHE 544 CG PHE 545 CD1 PHE 546 CD2 PHE 547 CEl PHE 548 CE2 PHE 549 CZ PHE 550 C PHE 551 0 PHE 552 N PRO 553 CD PRO 554 CA PRO 555 CB PRO 556 CG PRO 557 c PRO 558 0 PRO 559 N ILE 560 H ILE 561 CA ILE 562 CB ILE 563 CG2 ILE 564 CCI ILE 565 CD ILE 566 C ILE 567 0 ILE 568 N GLU 569 H GLU 570 CA GLU 571 CB GLU 572 CG GLU 573 CD GLU 574 OE. GLU 575 0E2 GLtJ 576 c GLU 577 0 GLU 578 N ARG 9.418 12.580 6.985 1.00 4.13 8.490 12.492 7.283 1.00 0.00 10.476 12.333 7.958 1.00 5.36 10.097 13.014 9.295 1.00 5.09 10.111 14.519 9.155 1.00 2.00 8.934 15.206 8.879 1.00 2.00 11.332 15.182 9.253 1.00 3.34 8.987 16.571 8.688 1.00 8.91 11.371 16.549 9.060 1.00 2.00 10.203 17.246 8.780 1.00 2.00 10.707 10.846 8.189 1.00 3.82 9.802 10.183 8.724 1.00 4.17 11.822 10.239 7.802 1.00 4.66 12.871 10.838 6.989 1.00 7.48 12.139 8.867 8.165 1.00 6.70 13 .388 8.558 7.392 1.00 4.95 13.453 9.621 6.300 1.00 5.79 12.313 8.715 9.672 1.00 10.66 12.935 9.532 10.350 1.00 8.35 11.681 7.687 10.217 1.00 11.15 11.116 7.128 9.646 1.00 0.00 11.807 7.337 11.621 1.00 7.78 10.408 7.155 12.247 1.00 6.02 10.620 6.819 13.710 1.00 4.07 9.524 8.398 12.103 1.00 4.03 8.035 8.155 12.396 1.00 2.00 12.563 6.013 11.574 1.00 8.52 12.018 5.034 11.047 1.00 9.02 13.816 5.975 12.022 1.00 9.62 14.202 6.797 12.395 1.00 0.00 14.612 4.756 12.035 1.00 8.61 16.077 5.015 11.900 1.00 8.30 16.575 5.629 10.615 1.00 29.69 18.027 6.097 10.749 1.00 43.17 18.878 5.304 11.173 1.00 46.59 18.305 7.262 10.441 1.00 47.06 14.464 4.023 13.348 1.00 9.33 14.321 4.691 14.365 1.00 11.22 14.460 2.698 13.370 1.00 9.50 0 .243 ATOM 579 H ARG 63 14.448 2.228 12.514 1.00 0.00 15 3 .2

A

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ATOM 580 ATOM 581 ATOM 582 ATOM 583 ATOM 584 ATOM 585 ATOM 586 ATOM 587 ATOM 588 ATOM 589 ATOM 590 ATOM 591 ATOM 592 ATOM 593 ATOM 594 ATOM 595 ATOM 596 ATOM 597 ATOM 598 ATOM 599 ATOM 600 ATOM 601 ATOM 602 ATOM 603 1 ATOM 504 1 ATOM 605 ATOM 606 ATOM 607 %TOM 608 ATOM 609 ATOM 610 ATOM 611 ATOM 612 ATOM 613 ATOM 614 TOM 615 TOM 616 TOM 617

NE

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14.508 13.851 13.612 12.825 12.614 11.709 13.596 14.864 15.125 15.553 13.293 12.349 14.009 15.992 16.882 16.312 15.586 17.692 17.809 17.253 18.029 17.579 19.246 19.593 19.721 18.196 17.384 19.498 20.086 20.112 21.589 22.134 21.972 23.666 19.306 19.098 18.737 18.751 1.918 0.583 -0.203 -1.422 -2.334 -2.419 -3 .072 -3.031 -2.426 -3.603 -3.916 -3.985 -4.480 1.760 1.405 2.083 2.240 2. 150 3. 120 4.507 5.265 5.524 5.681 5.484 6.197 0.803 -0.097 0.702 1. 426 -0.477 -0.172 0.937 0.566 1.012 -0.988 -2.185 -0.082 0.854 14.597 14.339 15.604 15.224 16.332 16.697 16.878 16.463 15.711 16.909 17.858 18.185 18.269 14.998 14.210 16.247 16.876 16.724 17.901 17.632 16.569 15.453 16.873 17.766 16.189 17.200 17. 379 17.519 17. 230 18. 145 18.629 19. 638 21.105 19.553 19.337 19.514 20.122 19.850 1.00 11.99 1.00 16.38 1.00 20.52 1.00 27.53 1.00 36.69 1.00 0.00 1.00 39.35 1.00 42.71 1.00 0.00 1.00 0.00 1.00 41.76 1.00 0.00 1.00 0.00 1.00 14.55 1.00 15.00 1.00 13.04 1.00 0.00 1.00 14.92 1.00 13.12 1.00 20.26 1.00 26.72 1.00 32.53 1.00 31.43 1.00 0.00 .O0 0.00 1.00 14.42 1.00 15.52 1.00 19.29 1.00 0.00 1.00 22.45 1.00 28.25 1.00 36.97 1.00 35.85 1.00 31.59 1.00 19.74 1.00 22.52 1.00 16.94 1.00 0.00 244

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618 CA ASN 619 CB ASN 620 CG ASN 621 ODI ASN 622 ND2 ASN 623 HD21 ASN 624 HD22 ASN 625 C ASN 626 o ASN 627 N GLY 628 H GLY 629 CA GLY 630 C GLY 631 0 GLY 632 N THR 633 H THR 634 CA THR 635 CB THR 636 OGI THR 637 HG1 THR 638 CG2 THR 639 C THR 640 0 THR 641 N TYR 642 H TYR 643 CA TYR 644 CB TYR 645 CG TYR 646 CDI TYR 647 CEI TYR 648 CD2 TYR 649 CE2 TYR 650 CZ TYR 651 OH TYR 652 HH TYR 653 C TYR 654 0 TYR 655 N ALA 656 H ALA 66 66 66 66 66 66 66 66 66 67 67 67 67 67 68 68 68 68 68 68 68 68 68 69 59 -9 -9 59 59 59 59 -69 g 9 -9 59 69 18.035 -0.443 21.344 1.00 14.28 18.407 0.567 22.433 1.00 17.49 18.149 2.027 22.091 1.00 18.94 17.411 2.357 21.159 1.00 20.48 18.776 2.964 22.771 1.00 26.84 19.427 2.694 23.459 1.00 0.00 18.577 3.906 22.593 1.00 0.00 16.531 -0.557 21.223 1.00 13.50 15.822 -0.693 22.219 1.00 11.14 16.013 -0.514 19.997 1.00 10.89 16.594 -0.368 19.219 1.00 0.00 14.604 -0.731 19.757 1.00 5.16 13.780 0.521 19.903 1.00 5.50 12.551 0.429 19.953 1.00 4.32 14.402 1.679 20.083 1.00 5.74 15.364 1.730 20.241 1.00 0.00 13.602 2.891 20.096 1.00 10.10 14.274 3.962 21.038 1.00 7.70 15.602 4.200 20.634 1.00 6.50 16.204 3.718 21.205 1.00 0.00 14.284 3.486 22.482 1.00 6.39 13.465 3.376 18.643 1.00 10.84 14.033 2.800 17.706 1.00 8.07 12.687 4.417 18.438 1.00 11.31 12.312 4.893 19.205 1.00 0.00 12.398 4.956 17.143 1.00 8.56 10.914 4.793 16.881 1.00 10.27 10.494 3.343 16.804 1.00 9.08 10.116 2.661 17.959 1.00 11.62 9.769 1.316 17.883 1.00 15.89 10.525 2.691 15.571 1.00 12.19 10.178 1.342 15.490 1.00 16.67 9.798 0.654 16.647 1.00 20.73 9.417 -0.682 16.573 1.00 17.13 9.258 -0.922 15.649 1.00 0.00 12.784 6.416 17.202 1.00 10.11 12.428 7.111 18.163 1.00 14.34 13.510 6.930 16.224 1.00 12.39 13.836 6.347 15.502 1.00 0.00 245

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657 658 659 660 661 662 663 664 665 666 667 668 669 670 671 672 673 674 675 676 677 678 679 680 681 682 683 684 685 686 687 688 689 690 691 692 693 694 695 CA ALA CB ALA C ALA 0 ALA N ILE H ILE CA ILE CB ILE CG2 ILE CG1 ILE CD ILE C ILE 0 ILE N ALA H ALA CA ALA CB ALA C ALA 0 ALA N GLY H GLY CA GLY C GLY 0 GLY N GLY H GLY CA GLY C GLY O GLY N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS 70 70 70 70 71 71 71 71 71 71 71 71 71 72 72 72 72 72 72 73 73 73 73 73 74 74 74 74 74 75 75 75 75 75 75 75 75 75 75 13 .886 15.239 14.013 14.523 13 .533 13 .071 13 .773 12 .896 13.255 11 .433 10.520 15.260 15 .714 16.085 15 .694 17 .517 18 .258 17 .808 17 .219 18 .672 19 .112 19 .052 17 .960 18 .049 16 .920 16 .913 15 .824 15 .825 16 .649 14. 817 14 .144 14. 668 13 695 14.384 13 .518 14.260 13 .448 12 .515 13 -918 8.334 8.583 8.833 8. 112 10. 060 10.526 10. 777 12 .060 12. 885 11.675 12.881 11. 117 11.412 11. 069 10. 895 11.313 11.340 12. 650 13.669 12. 625 11.771 13 .798 14. 265 15.366 13 .456 12. 572 13.787 12.895 11.983 13 .150 13 .806 12. 437 13. 172 14.383 15.120 16.420 17.330 17.427 18.257 16.185 16.848 14.753 13.875 14. 503 15.230 13.252 13.195 11. 969 13.158 13.246 13 .332 14.446 12.277 11.392 12.436 11. 128 13.095 12.737 14.108 14.299 14.882 15.834 16.389 16.033 15 .613 16.906 18.126 18.268 18.960 18.678 20.215 21.136 21.707 22.6~93 22.919 23.676 23.225 23.714 1.00 10.82 1.00 2.00 1.00 12.46 1.00 13.59 1.00 12.16 1.00 0.00 1.00 8.89 1.00 8.93 1.00 7.48 1.00 2.00 1.00 4.76 1.00 11.20 1.00 13.25 1.00 11.89 1.00 0.00 1.00 14.12 1.00 12.87 1.00 15.57 1.00 13 1.00 16.33 1.00 0.00 1.00 11.52 1.00 14.51 1.00 17.12 1.00 13.85 1.00 0.00 1.00 9.77 1.00 13 .72 1.00 12.11 1.00 12.83 1.00 0.00 1.00 14.60 1.00 15.05 1.00 11 .11 1.00 13.01 1.00 12.46 1.00 21.36 1.00 0.00 1.00 0.00 246 1 0 a.

1 5 ATOM 696 ATOM 697 ATOM 698 ATOM 699 ATOM 700 ATOM 701 ATOM 702 ATOM 703 ATOM 704 ATOM 705 ATOM 706 ATOM 707 ATOM 708 ATOM 709 ATOM 710 ATOM 711 ATOM 712 ATOM 713 ATOM 714 ATOM 715 ATOM 716 ATOM 717 ATOM 718 ATOM 719 ATOM 720 ATOM 721 ATOM 722 ATOM 723 %TOM 724 %TOM 725 ATOM 726 ATOM 727 kTOM 728 kTOM 729 kTOM 730 kTOM 721 kTOM 732 kTOM 733 kTOM 734 HZ3 LYS C LYS O LYS N ALA H ALA CA ALA CB ALA C ALA o ALA N HIS H HIS CA HIS CB HIS CG HIS CD2 HIS ND1 HIS HD1 HIS CEl HIS NE2 HIS HE2 HIS C HIS o HIS N CYS H CYS CA CYS CB CYS SG CYS C CYS O CYS N GLY H GLY CA GLY C GLY o GLY N PRO CD PRO CA PRO CB PRO CG PRO 75 75 75 76 76 76 76 76 76 77 77 77 77 77 77 77 77 77 77 77 77 77 78 78 78 78 78 78 78 79 79 79 79 79 80 80 80 80 80 13.329 14.178 13.270 14 .734 15.503 14.257 15.291 12.977 12.624 12.180 12.464 10.911 9 .751 9 .907 9 .429 10.514 11.053 10.418 9.768 9.596 10 .745 11. 253 10. 033 9 .625 9.884 9 .381 10.796 8.960 9 .005 8.128 8.169 7.212 6.762 7 .015 6 .089 6 .052 5 .496 5.005 4.852 16.962 11. 018 10. 809 10. 048 10.266 8.684 7.721 8.477 9.208 7.515 6.969 7.205 7.778 9.264 10.268 9.833 9.394 11. 122 11. 368 12.266 5.702 4.990 5.169 5.747 3.735 3.354 3.369 3.126 1.908 3.943 4.912 3.410 4.509 5.682 4.186 2.849 5.158 4.318 2.933 24.643 20.033 19.220 20.761 21. 322 20.683 21.213 21. 464 22.399 21 .027 20.258 21.658 20.879 20.582 21.371 19 .550 18 .851 19.680 20.778 21.126 21.692 20.834 22.660 23.326 22 .776 24.175 25.280 21.757 21.557 21.113 21. 228 20.145 19.210 19 .512 18.089 17.491 17.187 16.015 16 .571 1 .200 0.00 1.300 16.16 1.00 17.70 1.00 13.81 1.00 0.00 1.00 10.95 1.00 11.99 1.00 10.10 1.00 11.36 1.00 6.45 1.00 0.00 1.00 8.09 1.00 8.53 1.00 8.60 1.00 9.12 1.00 9.19 1.00 0.00 1.00 2.93 1.00 9.32 1.00 0.00 1.00 11.51 1.00 12.04 1.00 12.82 1.00o 0.00 1.20 14.28 1.30 11.77 1.00 9.90 1.00 16.98 1.00 17.80 1.00 15.68 1.00 0.00 1.00 11.88 1.00 14.80 1.00 12.62 1.00 16.78 1.00 13.56 1.00 15.14 1.00 18.70 1.00 14.52 247

O

ATOM 735 ATOM 736 ATOM 737 ATOM 738 ATOM 739 ATOM 740 ATOM 741 ATOM 742 ATOM 743 1 0 ATOM 744 ATOM 745 ATOM 746 ATOM 747 ATOM 748 1 5 ATOM 749 ATOM 750 ATOM 751 ATOM 752 ATOM 753 20 ATOM 754 ATOM 755 ATOM 756 ATOM 757 ATOM 758 ATOM 759 ATOM 760 ATOM 761 ATOM 762 ATOM 763 ATOM 764 ATOM 765 ATOM 766 ATOM 767 ATOM 768 ATOM 769 ATOM 770 ATOM 771 ATOM 772 ATOM 773 C PRO O PRO N ALA H ALA CA ALA CB ALA C ALA O ALA N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU OE2 GLU C GLU O GLU N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU 0 LEU N CYS H CYS CA CYS CB CYS SG CYS C CYS O CYS N GLU H GLU CA GLU CB GLU CG GLU 4.425 4.390 3.582 3.648 2.560 1.696 3.217 2.759 4.317 4.675 4.998 6.055 5.510 5.248 5.898 4.403 5.683 5.772 6.177 6.060 6.804 7.521 8.272 9.480 7.357 5.752 5.988 4.602 4.494 3.548 2.503 3.177 2.926 2.575 2.806 3.004 2.350 2.212 0.815 6.013 7.209 5.470 4.511 6.256 5.401 7.301 8.447 6.966 6.068 7.900 7.211 6.345 4.903 4.019 4.643 8.982 10.112 8.672 7.759 9.659 8.966 9.829 9.086 10.216 10.640 11.849 10.164 9.192 11.027 10.168 9.486 11.826 12.979 11.294 10.339 12.030 11.121 10.555 17.827 17.551 18.715 18.927 19.378 20.259 20.270 20.315 20.950 20.827 21.810 22.673 23.801 23.391 23.922 22.545 21.007 21.482 19.799 19.462 18.938 17.736 16.683 16.219 15.524 18.449 18.544 17.973 17.890 17.482 16.756 15.221 18.615 18.399 19.835 19.935 21.007 22.207 22.406 1.00 13.25 1.00 13.75 1.00 11.81 1.00 0.00 1.00 8.01 1.00 10.17 1.00 14.13 1.00 19.64 1.00 8.88 1.00 0.00 1.00 8.22 1.00 12.54 1.00 15.92 1.00 21.02 1.00 19.20 1.00 30.40 1.00 7.91 1.00 8.06 1.00 9.05 1.00 0.00 1.00 4.91 1.00 3.58 1.00 7.47 1.00 2.00 1.00 2.00 1.00 4.63 1.00 5.60 1.00 8.55 1.00 0.00 1.00 8.64 1.00 5.54 1.00 11.42 1.00 12.17 1.00 11.99 1.00 15.31 1.00 0.00 1.00 12.31 1.00 19.90 1.00 31.63 248

ATOM

ATOM

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ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

774 775 776 777 778 779 780 781 782 783 784 785 786 787 788 789 790 791 792 793 794 795 796 797 798 799 800 801 802 803 804 805 806 807 808 809 810 811 812 CD GLU OE1 GLU 0E2 GLU C GLU 0 GLU N PE H PHE CA PE CB PE CG PE CD1 PHE CD2 PE CEl PE CE2 PE CZ PE C PE 0 PHE N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR.

CE1 TYR CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR C TYR O TYR N SEP.

H SER CA SEP.

0.658 -0.477 1.642 3.333 2.920 4.631 4.937 5.603 6.999 8.114 8.400 8.808 9.375 9.781 10.064 5.575 5.446 5.653 5.691 5.666 6 .110 7.591 8 .021 9.391 8.525 9.891 10.316 11.668 12.181 4.352 4.319 3.248 3.264 2 .009 0.860 0.561 1.351 2.160 1.486 9 .495 9 .081 9 .071 13 .125 14 .260 12 .861 11.944 13 890 13 .293 14.317 14 .831 14.781 15 .816 15 .765 16.284 15. 027 16 .187 14 .760 13 826 15.833 15 .254 14 .946 13 .631 13 .356 15. 979 15 .713 14.396 14 .102 14.910 16 .586 17 .653 16 .094 15 .179 16 .852 15 .969 14. 907 14.368 17 .942 18 .970 23 .503 23.738 24.118 21.372 21. 571 21.416 21. 248 21.725 21. 764 21. 932 23.201 20.807 23.336 20.944 22.212 20.720 21.109 19.418 19.113 18.446 17.139 17. .117 17.046 16 .974 17 .117 17 .042 16.974 16.932 17.066 18.305 17.702 18 .857 19.207 18.979 19 .425 18.539 18 .429 20.036 19.995 1.00 39.27 1.00 41.21 1.00 42.94 1.00 6.87 1.00 10.13 1.00 4.59 1.00 0.00 1.00 6.95 1.00 4.93 1.00 5.40 1.00 2.19 1.00 2.76 1.00 2.93 1.00 2.30 1.00 5.55 1.00 9.00 1.00 14.30 1.00 11.37 1.00 0.00 1.00 6.03 1.00 3.16 1.00 2.00 1.00 5.05 1.00 8.26 1.00 2.00 1.00 2.00 1..00 6.27 1.00 7.53 1.00 0.00 1.00 3.38 1.00 5.53 1.00 7.17 1.00 0.00 1.00 6.67 1.00 6.09 1.00 23.12 1.00 0.00 1.00 9.31 1.00 5.17

SER

SEP.

SEP.

SEP.

SEP.

249 ATOM 813 N ARlG 89 3.017 17.673 21.027 1.00 15.78 *5 S a ATOM 814 H ARG 89 3.530 16.838 ATOM 815 CA ARG 89 3.262 18.543 ATOM 816 CB ARG 89 3.587 17.742 ATOM 817 CG ARG 89 2.563 16.693 ATOM 818 CD ARG 89 2.997 15.851 ATOM 819 NE ARG 89 4.239 15.083 ATOM 820 HE ARG 89 5.061 15.540 ATOM 821 CZ ARG 89 4.296 13.764 ATOM 822 NH1 ARG 89 3.207 13.079 ATOM 823 HH11 ARG 89 2.324 13.538 ATOM 824 HH12 ARG 89 3.280 12.100 ATOM 825 NH2 ARG 89 5.469 13.119 ATOM 826 HH21 ARG 89 6.295 13.619 15 ATOM 827 HH22 ARG 89 5.518 12.140 ATOM 828 C ARG 89 4.444 19.469 ATOM 829 O ARG 89 4.507 20.553 ATOM 830 N ASP 90 5.421 19.082 ATOM 831 H ASP 90 5.407 18.181 ATOM 832 CA ASP 90 6.582 19.891 ATOM 833 CB ASP 90 7.626 19.502 ATOM 834 CG ASP 90 8.925 20.286 ATOM 835 OD1 ASP 90 9.737 19.962 ATOM 836 OD2 ASP 90 9.156 21.203 ATOM 837 C ASP 90 7.039 19.587 ATOM 838 O ASP 90 7.512 18.482 ATOM 839 N PRO 91 6.917 20.560 ATOM 840 CD PRO 91 6.233 21.831 ATOM 841 CA PRO 91 7.434 20.495 ATOM 842 CB PRO 91 7.287 21.916 ATOM 843 CG PRO 91 7.060 22.761 ATOM 844 C PRO 91 8.844 19.968 ATOM 845 O PRO 91 9.173 19.194 ATOM 846 N ASP 92 9.683 20.419 ATOM 847 H ASP 92 9.364 21.117 ATOM 848 CA ASP 92 11.043 19.991 ATOM 849 CB ASP 92 11.007 18.818 ATOM 850 CG ASP 92 12.355 18.438 ATOM 851 OD1 ASP 92 13.246 19.264 20.985 22.175 23.444 23.853 25.067 24.955 24.679 25.223 25.601 25.696 25.792 25.157 24.899 25.357 21.928 22.493 21.131 20.738 20.903 21.966 22.048 22.905 21.267 19.478 19.202 18.560 18.781 17.196 16.672 17.913 17.102 16.210 18.028 18.631 18.195 19.198 19.826 20.003 1.00 0.00 1.00 19.64 1.00 18.92 1.00 28.31 1.00 36.85 1.00 42.21 1.00 0.00 1.00 44.61 1.00 46.06 1.00 0.00 1.00 0.00 1.00 44.47 1.00 0.00 1.00 0.00 1.00 18.88 1.00 20.00 1.00 18.60 1.00 0.00 1.00 16.39 1.00 12.09 1.00 10.44 1.00 21.16 1.00 19.94 1.00 19.96 1.00 20.24 1.00 15.46 1.00 17.20 1.00 14.01 1.00 16.08 1.00 12.13 1.00 14.28 1.00 16.05 1.00 12.31 1.00 0.00 1.00 10.93 1.00 5.10 1.00 8.25 1.00 14.68 250 ATOM 852 OD2 ASP 92 12.549 17.275 20.136 1.00 12.78

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20 ATOM

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853 854 855 856 857 858 859 860 861 862 863 864 865 866 867 868 869 870 871 872 873 874 875 876 877 878 879 880 881 882 883 884 885 886 887 888 889 C ASP O ASP N GLY H GLY CA GLY C GLY O GLY N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N PRO CD PRO CA PRO CB PRO CG PRO C PRO O PRO N CYS H CYS CA CYS CB CYS SG CYS C CYS O CYS N ASN H ASN CA ASN CB ASN CG ASN OD1 ASN ND2 ASN 11.829 19.653 12.501 18.619 11.772 20.607 11.235 21.419 12.563 20.488 11.725 20.330 12.192 20.497 10.493 19.914 10.225 19.703 9.523 19.788 8.308 19.012 8.411 17.587 7.031 17.090 8.999 16.780 9.063 21.176 9.223 22.166 8.485 21.309 8.563 20.350 7.915 22.559 7.452 22.217 7.348 20.732 6.847 23.113 6.668 24.329 6.072 22.244 6.248 21.287 5.039 22.624 3.753 23.076 2.809 22.013 4.764 21.420 5.459 20.411 3.839 21.448 3.208 22.196 3.559 20.279 3.041 20.641 1.691 21.326 1.546 22.385 0.651 20.865 0.764 20.069 16.932 16.798 16.009 16.141 14.786 13.537 12.408 13.762 14.675 12.708 13.188 13.597 13.966 12.463 12.237 12.969 11.034 9.925 10.591 9.186 9.137 11.518 11.647 12.136 12.022 13.080 12.334 11.202 13.974 13.826 14.931 15.012 15.739 17.155 17.216 16.618 17.900 18.469 1.00 12.54 1.00 13.03 1.00 12.18 1.00 0.00 1.00 13.73 1.00 8.10 1.00 11.87 1.00 4.57 1.00 0.00 1.00 10.89 1.00 3.94 1.00 3.94 1.00 2.31 1.00 11.05 1.00 13.55 1.00 11.66 1.00 14.27 1.00 7.51 1.00 13.61 1.00 10.57 1.00 8.09 1.00 13.42 1.00 16.04 1.00 14.57 1.00 0.00 1.00 12.49 1.00 13.81 1.00 10.86 1.00 11.03 1.00 10.72 1.00 8.03 1.00 0.00 1.00 7.35 1.00 4.07 1.00 6.44 1.00 17.31 1.00 6.94 1.00 0.00 ATOM 890 HD21 ASN 251 ATOM 891 HD22 ASN AO 89 HD2AN 97 -0.206 21.300 17.743 1.00 0.00 ATOM 892 ATOM 893 ATOM 894 ATOM 895 ATOM 896 ATOM 897 ATOM 898 ATOM 899 ATOM 900 ATOM 901 ATOM 902 ATOM 903 ATOM 904 1 5 ATOM 905 ATOM 906 ATOM 907 ATOM 908 ATOM 909 ATOM 910 ATOM 911 ATOM 912 C ASN O ASN N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LWU O LWU N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NH1 ARG 5 *5 S S S

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2.486 1.770 2 .347 2 .886 1.356 1. 685 3 .068 3 .206 3 .254 0.019 -0.117 -0 .969 -0 .853 -2 .257 -2 .520 -1.461 -1 .525 -0.269 0 .463 -0.038 -0 .942 -1.836 -0 .723 1 .126 1 .813 1 .302 -3 .269 -3 .328 -4 .050 -3 .918 -5 .053 -6 .150 -7 .259 -7 988 -8.924 -8.227 -7 .665 -7 .598 19.489 19.991 18.236 17.927 17.353 15.889 15.393 13.928 15 .611 17.761 17.920 17.998 17.785 18.422 19 .819 20.810 22.166 22 .879 22 .410 24.108 24.777 24.374 25.694 24.694 24.226 25.617 17.374 16.338 17 .477 18.213 16.439 17.030 16 .096 16.782 15 .887 14.874 14.285 15.329 15.026 14.156 15.423 16.180 14 .839 15.187 14.737 15.097 13.231 15.393 16.599 14.552 13 .605 15.030 14.458 14.959 14.292 14.499 14.946 14.024 13.321 13 .127 12.986 14 .265 14 .820 13.927 14.595 15.272 13.516 12.869 13 .215 12.293 11.791 10.629 9 .811 9 .034 9 .681 8.342 1.00 8.28 1.00 10.98 1.00 12.14 1.00 0.00 1.00 10.83 1.00 7.32 1.00 6.54 1.00 7.62 1.00 2.41 1.00 9.96 1.00 14.76 1.00 12.00 1.00 0.00 1.00 11.66 1.00 12.20 1.00 9.52 1.00 10.29 1.00 11.13 1.00 0.00 1.00 6.20 1.00 10.93 1.00 0.00 1.00 0.00 1.00 4.38 1.00 0.00 1.00 0.00 1.00 16.11 1.00 19.03 1.00 16.69 1.00 0.00 1.00 20.22 1.00 22.25 1.00 30.42 1.00 38.20 1.00 42.38 1.00 46.25 1.00 0.00 1.00 0.00

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913 HH11 ARG 914 HH12 ARG 915 NH2 ARG 916 HH21 ARG 917 HH22 ARG 918 C ARG 919 0 AP.G 920 N LYS 921 H LYS 922 CA LYS 923 CB LYS 924 CG LYS 925 CD LYS 926 CE LYS 927 NZ LYS 928 HZ1 LYS 929 HZ2 LYS .252 15 ATOM 930 HZ3 LYS 100 ATOM 931 C LYS 100 ATOM 932 O LYS 100 ATOM 933 N PRO 101 ATOM 934 CD PRO 101 ATOM 935 CA PRO 101 ATOM 936 CB PRO 101 ATOM 937 CG PRO 101 ATOM 938 C PRO 101 ATOM 939 O PRO 101 ATOM 940 N CYS 102 ATOM 941 H CYS 102 ATOM 942 CA CYS 102 ATOM 943 CB CYS 102 ATOM 944 SG CYS 102 ATOM 945 C CYS 102 ATOM 946 O CYS 102 ATOM 947 N ASN 103 ATOM 948 H ASN 103 ATOM 949 CA ASN 103 ATOM 950 CB ASN 103 ATOM 951 CG ASN 103 ATOM 952 OD1 ASN 103 ATOM 953 ND2 ASN 103 ATOM 954 HD21 ASN 103 ATOM 955 HD22 ASN 103 ATOM 956 C ASN 103 ATOM 957 O ASN 103 ATOM 958 N ARG 104 ATOM 959 H ARG 104 ATOM 960 CA ARG 104 ATOM 961 CB ARG 104 ATOM 962 CG ARG 104 ATOM 963 CD ARG 104 ATOM 964 NE ARG 104 ATOM 965 HE ARG 104 ATOM 966 CZ ARG 104 ATOM 967 NH1 ARG 104 ATOM 968 HH11 ARG 104 -4.432 -3.696 -4.669 -5.370 -4.277 -4.602 -5.819 -5.030 -6.262 -4.343 -3.391 -5.048 -4.153 -4.935 -5.393 -4.678 -6.550 -7.043 -7.044 -8.144 -7.592 -6.421 -8.372 -9.323 -7.943 -7.569 -8.330 -7.178 -6.631 -7.597 -7.267 -5.860 -6.139 -5.367 -4.399 -5.879 -7.180 -7.808 15.183 15.275 13.987 13.784 12.708 11.755 12.361 12.465 12.590 12.176 12.015 11.857 12.171 11.867 10.362 9.431 10.168 10.958 8.843 8.940 9.244 9.068 9.703 9.825 9.918 8.118 8.700 6.847 6.474 5.971 4.514 3.941 2.498 2.175 2.204 1.729 1.522 1.680 12.566 11.569 13.131 14.388 12.564 13.678 14.308 11.269 11.215 10.182 10.264 8.941 7.768 6.165 9.002 8.600 9.618 9.927 9.919 10.978 12.364 12.663 13.314 13.123 14.169 .8.716 7.939 8.614 9.337 7.538 7.782 7.783 8.209 9.396 9.337 10.539 10.699 9.936 1.00 16.85 1.00 15.54 1.00 13.08 1.00 7.49 1.00 11.31 1.00 6.33 1.00 3.78 1.00 10.35 1.00 12.69 1.00 9.14 1.00 0.00 1.00 11.88 1.00 11.92 1.00 13.71 1.00 12.91 1.00 11.19 1.00 10.89 1.00 0.00 1.00 11.19 1.00 8.17 1.00 8.17 1.00 15.63 1.00 15.55 1.00 0.00 1.00 0.00 1.00 8.63 1.00 9.71 1.00 9.83 1.00 0.00 1.00 6.25 1.00 8.62 1.00 3.24 1.00 10.70 1.00 18.79 1.00 0.00 1.00 21.66 1.00 28.57 1.00 0.00 -8.923 14.282 8.536 1.00 0.00 253 9* ATOM 969 ATOM 970 ATOM 971 ATOM 972 ATOM 973 ATOM 974 ATOM 975 ATOM 976 ATOM 977 1 0 ATOM 978 ATOM 979 ATOM 980 ATOM 981 ATOM 982 1 5 ATOM 983 ATOM 984 ATOM 985 ATOM 986 ATOM 987 ATOM 988 ATOM 989 ATOM 990 ATOM 991 ATOM 992 ATOM 993 ATOM 994 ATOM 995 ATOM 996 ATOM 997 ATOM 998 ATOM 999 ATOM 1000 ATOM 1001 ATOM 1002 ATOM 1003 ATOM 1004 ATOM 1005 ATOM 1006 ATOM 1007

PRO

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PRO

PRO

o PRO N SER H SER CA SER CB SER OG SER HG SER C SER O SER N GLY H GLY CA GLY C GLY o GLY N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N GLU H GLU CA GLU CB GLU HH12 ARG NH2 ARG HH21 ARG HH22 ARG C ARG 0 ARG 104 104 104 104 104 104 105 105 105 105 105 105 105 106 106 106 106 106 106 106 106 107 107 107 107 107 108 108 108 108 108 108 108 108 108 109 109 109 109 -7 523 -5.056 -4.083 -5.413 -9-101 -9 .787 -9 .660 -8.924 -11.091 -11 .213 -10.017 -11. 695 -10.991 -12 .999 -13 .535 -13 .664 -15. 140 -15.313 -14.780 -13 .520 -13 672 -13 132 -12 849 -12 .980 -11 576 -11 .188 -10.765 -11. 032 -9 .414 -8 .874 -7 .414 -7 .261 -6 .960 -8 .654 -8.771 -7 .921 -7.853 -7.127 -7.309 1.167 1.550 1.765 1.212 6.043 6.062 6.168 6.498 6.079 6.227 7.060 4.775 3.768 4.738 5.558 3 .505 3 .789 4.735 4.508 2.430 2 .683 1.232 1.128 0 .119 0 .059 -0.959 1 ill 1.900 1.042 2.413 2.431 1.578 3 .852 0.500 0.954 -0.543 -0.782 -1.275 -2.773 11.568 11.575 11.484 12.445 7.449 8.477 6.249 5.033 6.010 4.521 4.161 6.517 6.660 6.776 6.746 7.149 7.401 8.445 9.214 6.063 4.865 6.509 7.440 5.609 5.036 4.456 5.178 5.692 4.673 4.278 3.836 2.612 3.576 5.862 7.001 5.533 4.585 6.481 6.230 1.00 0.00 1.00 30.06 1.00 0.00 1.00 0.00 1.00 9.23 1.00 11.51 1.00 13.97 1.00 10.44 1.00 14.04 1.00 16.08 1.00 15.10 1.00 18.06 1.00 18.50 1.00 21.15 1.00 0.00 1.00 21.87 1.00 22.16 1.00 25.97 1.00 0.00 1.00 23.43 1.00 20.97 1.00 21.55 1.00 0.00 1.00 20.51 1.00 24.96 1.00 27.67 1.00 22.03 1.00 0.00 1.00 16.09 1.00 12.09 1.00 10.25 1.00 11.68 1.00 12.09 1.00 12.99 1.00 12.44 1.00 14.56 1.00 0.00 1.00 13.90 1.00 19.29 254 ATOM 1008 CG GLU

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ATOM

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1 5 ATOM

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20 ATOM

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1009 CD GLU 1010 OE1 GLU 1011 0E2 GLU 1012 C GLU 1013 0 GLU 1014 N PRO 1015 CD PRO 1016 CA PRO 1017 CB PRO 1018 CG PRO 1019 C PRO 1020 0 PRO 1021 N GLN 1022 H GLN 1023 CA GLN 1024 CB GLN 1025 CG GLN 1026 CD GLN 1027 QEl GLN 1028 NE2 GLN 1029 HE21 GLN 1030 HE22 GLN 1031 C GLN 1032 0 GLN 1033 N PRO 1034 CD PRO 1035 CA PRO 1036 CB PRO 1037 CG PRO 1038 c PRO 1039 0 PRO 1040 N GLY 1041 H GLY 1042 CA GLTY 1043 C GLY 1044 0 GLY 1045 N VAL 1046 H VAL 109 109 109 109 109 109 110 110 110 110 110 110 110 112 112 112 112 112 112 112 113 113 113 113 113 112 112 -8.738 -3.284 -9.520 -3 .230 -10.270 -2.277 -9.388 -4.168 -5.695 -0.866 -5.398 -0.456 -4.758 -0.979 -4.984 -1.282 -3 .339 -0.915 -2.674 -1.303 -3.664 -0.827 -2 .896 -1.785 -3.310 -2.924 -2 .008 -1.294 653 -0.395 -1.593 -1.998 -1.157 -0.944 -0.638 -1.453 646 -2.233 -2.850 -2 .233 6.141 1.00 29.48 7.441 1.00 40.66 7.666 1.00 45.63 8.223 1.00 51.26 6.231 1.00 8.40 5.114 1.00 10.50 7.155 1.00 5.95 8.564 1.00 5.24 6.861 1.00 10.05 8.175 1.00 4.68 9.198 1.00 4.54 5.680 1.00 7.66 5 .536 1.00 11.84 4 .838 1.00 10.25 5 .008 1.00 0.00 3 .637 1.00 8.90 2.610 1.00 2.00 1.268 1.00 8.79 0.449 1.00 5.34 0.684 1.00 5.86 -1.177 -2.954 -0.536 1.00 6.33 -0.210 -2.930 -0.716 1.00 0.00 -1.812 -3.537 -1.006 1.00 0.00 -0.493 -3 .010 3 .891 1.00 8.54 0.573 -2.599 4 .345 1.00 5.96 -0.673 -4.308 3 .579 1.00 9.29 -1.931 -4.872 3 .075 1.00 7.95 0.366 -5.332 3.622 1.00 5.72 -0.244 -6.558 2.999 1.00 5.42 -1.719 -6.364 3 .178 1.00 5.05 1. 647 -4.955 2.921 1.00 6.46 1. 636 -4.369 1.839 1.00 6.87 2.766 -5.354 3.510 1.00 6.40 2.703 -5.962 4.274 1.00 0.00 4 .046 -5.056 2.945 1.00 6.46 4. 653 -6.303 2.353 1.00 8.56 4 .674 -7.344 3 .011 1.00 13.23 5 .213 -6.187 1.155 1.00 4.67 5 .187 -5.284 0.757 1.00 0.00 -255 ATOM 1047 CA VAL 114 5.865 -7.249 0.419 1.00 4.61 6.315 -6.694 -0.990 1.00 3.22 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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ATOM

ATOM

1 5 ATOM

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20 ATOM

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1048 CB VAL 1049 CG1 VAL 1050 CG2 VAL 1051 C VAL 1052 0 VAL 1053 N PHE 1054 H PHE 1055 CA PHE 1056 CB PHE 1057 CG PHE 1058 CD1 PHE 1059 CD2 PHE 1060 CEl PHE 1061 CE2 PHE 1062 CZ PHE 1063 C PI-E 1064 0 PHE 1065 N ASP 1066 H ASP 1067 CA ASP 1068 CB ASP 1069 CG ASP 1070 ODi ASP 1071 0D2 ASP 1072 C ASP 1073 o ASP 1074 N CYS 1075 H CYS 1076 CA CYS 1077 CB CYS 1078 SG CYS 1079 C CYS 1080 0 CYS 1081 N LEU 1082 H LEU 1083 CA LEU 1084 CB LEU 114 114 114 114 114 115 115 115 115 115 115 115 115 115 115 115 115 116 116 116 116 116 116 116 116 116 117 117 117 117 117 117 117 118 118 118 118 118 7.105 -7.719 5.102 -6.401 7.035 -7.793 7.054 -9.006 7.975 -7.002 7.899 -6.033 9.090 -7.562 10.118 -6.486 11.542 -6.975 12.012 -8.211 12.423 -6.132 13.340 -8.584 13.756 -6.511 14.213 -7.732 8.579 -8.229 9.145 -9.245 7.515 -7.717 7.189 -6.839 6.901 -8.348 5.707 -7.554 5.989 -6.246 7.132 -5.815 5.026 -5.653 6.394 -9.762 6.621 -10.666 5.675 -9.910 5.429 -9.094 5.170 -11.181 4.341 -10.980 2.747 -10.208 6.332 -12.097 6.327 -13.261 7.372 -11.579 7.373 -10.622 8.534 -12.362 9.533 -11.502 10.691 -12.257 -1.741 1.00 3.86 -1.877 1.00 2.00 1.206 1.00 4.93 1.413 1.00 10.35 1.730 1.00 6.39 1.601 1.00 0.00 2.483 1.00 6.83 2.878 1.00 7.30 3.148 1.00 2.90 2.690 1.00 2.00 3.827 1.00 7.94 2.900 1.00 2.00 4.036 1.00 4.71 3.568 1.00 4.45 3.744 1.00 6.82 4.138 1.00 10.26 4.372 1.00 7.65 4.082 1.00 0.00 5.542 1.00 9.49 6.057 1.00 3.65 6.768 1.00 10.72 6.873 1.00 10.46 7.242 1.00 12.59 5.278 1.00 8.07 6.092 1.00 8.78 4.162 1.00 5.88 3.680 1.00 0.00 3.662 1.00 7.52 2.386 1.00 2.00 2.720 1.00 5.27 3.342 1.00 5.36 3.729 1.00 12.91 2.716 1.00 2.00 2.486 1.00 0.00 2.404 1.00 3.50 1.607 1.00 7.77 0.967 1.00 2.00 ATOM 1085 CG LEU 256 ATOM 1086 CD1 LEU 118 10.302 -12.739 16 .0 1.1 -0.416 1.00 10.01 ATOM 1087 CD2 LETJ 118 11.873 -11.362 0.852 1.00 2.00 ATOM 1088 C LEU 118 9.207 -12.888 3.672 1.00 7.78 ATOM 1089 0 LEU 118 9.371 -14.097 3.878 1.00 14.19 ATOM 1090 N ARG 119 9.570 -11.996 4.586 1.00 8.62 ATOM 1091 H ARG 119 9.355 -11.059 4.427 1.00 0.00 ATOM 1092 CA ARG 119 10.267 -12.355 5.802 1.00 6.69 ATOM 1093 CB ARG 119 10.642 -11.148 6.609 1.00 3.95 ATOM 1094 CG ARG 119 11.653 -10.284 5.927 1.00 4.79 1 0 ATOM 1095 CD ARG 119 11.994 -9.159 6 .864 1.00 10.98 ATOM 1096 NE ARG 119 10.818 -8.346 7.066 1.00 16.70 ATOM 1097 HE ARG 119 10.122 -8.329 6 .375 1.00 0.00 ATOM 1098 CZ ARG 119 10.663 -7.617 8 .160 1.00 19.41 ATOM 1099 NH1 ARG 119 11.579 -7.589 9 .132 1.00 24.20 1. 15 ATOM 1100 HH11 ARG 119 12.412 -8.139 9 .057 1.00 0.00 *ATOM 1101 HH12 ARG 119 11.421 -7.034 9 .948 1.00 0.00 *ATOM 1102 NH2 ARG 119 9.541 -6.930 8.271 1.00 17.87 *ATOM 1103 HH21 ARG 119 8.858 -6.988 7.541 1.00 0.00 ATOM 1104 HH22 ARG 119 9.373 -6.357 9.072 1.00 0.00 20 ATOM 1105 C ARG 119 9.472 -13.239 6.700 1.00 7.52 *ATOM 1106 0 ARG 119 10.066 -14.043 7.407 1.00 12.31 ATOM 1107 N ASP 120 8.151 -13.126 6.680 1.00 9.60 ATOM 1108 H ASP 120 7.743 -12.422 6 .133 1.00 0.00 *ATOM 1109 CA ASP 120 7.299 -13.966 7.478 1.00 7.93 ATOM 1110 CB ASP 120 5.844 -13.534 7 .320 1.00 7.93 ATOM 1111 CG ASP 120 4.844 -14.338 8.161 1.00 15.41 ATOM 1112 ODi ASP 120 4.818 -14.250 9 .396 1.00 15.27 ATOM 1113 0D2 ASP 120 4.075 -15.076 7.561 1.00 17.76 ATOM 1114 C ASP 120 7.480 -15.388 6 .996 1.00 13.71 ATOM 1115 0 ASP 120 7.696 -16.290 7.814 1.00 12.77 ATOM 1116 N ALA 121 7.454 -15.565 5 .667 1.00 9.90 ATOM 1117 H ALA 121 7.350 -14.790 5 .071 1.00 0.00 ATOM 1118 CA ALA 121 7.575 -16.873 5 .067 1.00 8.78 ATOM 1119 CB ALA 121 7.243 -16.761 3 .570 1.00 4.63 ATOM 1120 c ALA 121 8.965 -17.446 5 .267 1.00 6.18 ATOM 1121 0 ALA 121 9.119 -18.625 5 .604 1.00 11.46 ATOM 1122 N MET 122 10.012 -16.646 5.142 1.00 9.21 ATOM 1123 H MET 122 9.854 -15.711 4 .890 1.00 0.00 ATOM 1124 CA MET 122 11.368 -17.142 5.331 1.00 12.95 257

ATOM

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15 ATOM

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20 ATOM

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ATOM

1125 CB MET 122 1126 CG MET 122 1127 SD MET 122 1128 CE MET 122 1129 C MET 122 1130 0 MET 122 1131 N VAL 123 1132 H VAL 123 1133 CA VAL 123 1134 CB VAL 123 1135 CG1 VAL 123 1136 CG2 VAL 123 1137 C VAL 123 1138 0 VAL 123 1139 N ARG 124 1140 H ARG 124 1141 CA ARG 124 1142 CB ARG 124 1143 CG ARG 124 1144 CD ARG 124 1145 NE ARG 124 1146 HE ARG 124 1147 CZ ARG 124 1148 NH1 ARG 124 1149 HH11 ARG 124 1150 HH12 ARG 124 1151 NH2 ARG 124 1152 HH21 ARG 124 1153 HH22 ARG 124 1154 C ARG 124 1155 0 ARG 124 1156 N ASP 125 1157 H ASP 125 1158 CA ASP 125 1159 CB ASP 125 1160 CG ASP 125 1161 ODi ASP 125 1162 0D2 ASP 125 1163 C ASP 125 12.397 -16.141 12.235 -15.697 13.633 -14.669 13.348 -13.208 11.665 -17.462 12.376 -18.420 11.153 -16.686 10.655 -15.882 11.331 -16.955 10.805 -15.703 10.469 -15.927 11.945 -14.692 10.594 -18.255 11.187 -19.111 9.342 -18.449 8.898 -17.702 8.594 -19.687 7.245 -19.585 6.392 -20.857 4.913 -20.641 4.293 -19.885 4.020 -20.375 4.085 -18.568 4.424 -17.850 4.843 -18.283 4.251 -16.869 3.587 -17.946 3.381 -18.461 3.424 -16.959 9.360 -20.879 9.503 -21.882 9.926 -20.747 9.827 -19.897 10.715 -21.802 11.096 -21.389 11.702 -22.503 10.972 -23.416 12.899 -22.469 11.970 -22.077 4.868 3.430 2.923 3.865 6.785 7.076 7.730 7 .474 9.146 9.903 11. 378 9.816 9.500 10 .163 9.049 8 .593 9.247 8.554 8.581 8.301 9.383 10.184 9.313 8.232 7.433 8 .234 10.370 11. 201 10.340 8.713 9.406 7.519 7.038 6 .909 5.486 4 .645 4.269 4.358 7.727 1.00 13.19 1.00 6.17 1.00 13.61 1.00 22.78 1.00 15.80 1.00 18.09 1.00 17.27 1.00 0.00 1.00 18.34 1.00 14.82 1.00 7.76 1.00 11.65 1.00 20.45 1.00 22.11 1.00 18.15 1.00 0.00 1.00 15.36 1.00 11.87 1.00 12.47 1.00 8.51 1.00 12.39 1.00 0.00 1.00 13 .51 1.00 11.97 1.00 0.00 1.00 0.00 1.00 10.34 1.00 0.00 1.00 0.00 1.00 15.60 1.00 18.62 1.00 20.33 1.00 0.00 1.00 21.31 1.00 21.39 1.00 27.25 1.00 34.81 1.00 31.46 1.00 23.47 258 0*

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1 5 ATOM

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20 ATOM

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1164 1165 1166 1167 1168 1169 1170 1171 1172 1173 1174 1175 1176 1177 1178 1179 1180 1181 1182 1183 1184 1185 1186 1187 1188 1189 1190 1191 1192 1193 1194 1195 1196 O ASP N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CEl TYR CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR C TYR o TYR N VAL H VAL CA VAL CB VAL CG1 VAL CG2 VAL C VAL 0 VAL N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NH1 ARG 125 126 126 126 126 126 126 126 126 126 126 126 126 126 126 127 127 127 127 127 127 127 127 128 128 128 128 128 128 128 128 128 128 128 128 128 128 128 128 12 .253 -2 3.23 0 12.745 -21.070 12.467 -20.160 13 .942 -21.267 14.635 -19.916 15.783 -19.899 17.104 -20.144 18.145 -20.102 15.511 -19.613 16.546 -19.577 17.861 -19.813 18.902 -19.727 19-731 -19.774 13.646 -21.923 14.406 -22.816 12.631 -21.526 12.049 -20.807 12-377 -22.137 11.246 -21.401 10. 876 -22.108 11.731 -20.002 12.011 -23.603 12.647 -24.446 11.060 -23.912 10.583 -23.176 10.661 -25.264 9.644 -25.176 9.141 -26.500 8.025 -26.280 8.493 -25.548 9-341 -25.807 7.797 -24.530 6 .632 -24.107 6-238 -24.538 6.166 -23.334 8.284 -23.930 9.152 -24.244 7.797 -23.165 11-859 -26.103 8 .042 8.118 7 .902 8 .901 9 .133 10.150 9.730 10.667 11.506 12 .439 12.012 12.929 12 .446 10.239 10.619 11.013 10 .687 12.317 13 .053 14 .356 13 .403 12 .144 12.772 11.258 10 .812 10 .923 9 .804 9.265 8 .265 7 .104 6 .688 6 .581 7 .082 7 .894 6 .649 5 .502 5 .115 5 .082 10.505 1.00 24.12 1.00 21.49 1.00 0.00 1.00 19.50 1.00 25.90 1.00 29.35 1.00 27.77 1.00 31.52 1.00 28.26 1.00 30.56 1.00 35.32 1.00 40.70 1.00 0.00 1.00 21.90 1.00 25.30 1.00 19.39 1.00 0.00 1.00 19.85 1.00 17.19 1.00 16.84 1.00 17.80 1.00 22.88 1.00 22.13 1.00 24.55 1.00 0.00 1.00 22.77 1.00 23.22 1.00 26.51 1.00 26.64 1.00 31.22 1.00 0.00 1.00 35.88 1.00 34.74 1.00 0.00 1.00 0.00 1.00 40.92 1.00 0.00 1.00 0.00 1.00 25.38 ATOM 1197 H11 ARG ATOM 1198 HH12 ARG ATOM 1199 NH2 ARG ATOM 1200 HH21 ARG ATOM 1201 HH22 ARG ATOM 1202 C ARG -259 ATOM 1203 o ARG 128 11.996 -27.258 10.905 1.00 31.19 ATOM 1204 N GLN 129 12.763 -25.555 9.706 1.00 27.63 ATOM 1205 H GLN 129 12.611 -24.646 9.375 1.00 0.00 ATOM 1206 CA GLN 129 13.945 -26.270 9.289 1.00 30.34 ATOM 1207 CB GLN 129 14.576 -25.497 8.155 1.00 29.95 ATOM 1208 CG GLN 129 13.868 -25.769 6.847 1.00 32.24 ATOM 1209 CD GLN 129 14.365 -27.031 6.177 1.00 38.31 ATOM 1210 OE1 GLN 129 14.088 -28.153 6.591 1.00 43.39 ATOM 1211 NE2 GLN 129 15.146 -26.896 5.116 1.00 41.97 1 0 ATOM 1212 HE21 GLN 129 15.362 -25.995 4.785 1.00 0.00 ATOM 1213 HE22 GLN 129 15.498 -27.716 4.717 1.00 0.00 ATOM 1214 C GLN 129 14.931 -26.488 10.436 1.00 35.26 ATOM 1215 0 GLN 129 15.086 -27.639 10.857 1.00 35.05 ATOM 1216 N THR 130 15.534 -25.453 11.045 1.00 39.04 15 ATOM 1217 H THR 130 15.356 -24.543 10.735 1.00 0.00 0: ATOM 1218 CA THR 130 16.514 -25.655 12.114 1.00 38.84 @0 ATOM 1219 CB THR 130 17.282 -24.342 12.434 1.00 41.46 0@ ATOM 1220 OGI THR 130 16.840 -23.271 11.602 1.00 35.92 ATOM 1221 HG1 THR 130 15.925 -23.048 11.823 1.00 0.00 ATOM 1222 CG2 THR 130 18.766 -24.585 12.221 1.00 39.34 ATOM 1223 C THR 130 15.985 -26.204 13.436 1.00 37.73 ATOM 1224 0 THR 130 16.698 -26.948 14.113 1.00 40.99 ATOM 1225 N TRP 131 14.773 -25.865 13.868 1.00 34.87 ATOM 1226 H TRP 131 14.215 -25.292 13.309 1.00 0.00 ATOM 1227 CA TRP 131 14.227 -26.388 15.111 1.00 35.73 ATOM 1228 CB TRP 131 13.480 -25.284 15.867 1.00 36.36 ATOM 1229 CG TRP 131 14.343 -24.072 16.164 1.00 38.36 ATOM 1230 CD2 TRP 131 15.380 -24.020 17.052 1.00 39.04 ATOM 1231 CE2 TRP 131 15.821 -22.709 16.869 1.00 40.13 ATOM 1232 CE3 TRP 131 16 .020 -24.847 17.975 1.00 44.19 ATOM 1233 CD1 TRP 131 14.152 -22.898 15.494 1.00 38.77 ATOM 1234 NEI TRP 131 15.071 -22.093 15.951 1.00 37.02 ATOM 1235 HE1 TRP 131 15.199 -21.145 15.686 1.00 0.00 ATOM 1236 CZ2 TRP 131 16.901 -22.200 17.596 1.00 44.06 ATOM 1237 CZ3 TRP 131 17.105 -24.344 18.706 1.00 43.68 ATOM 1238 CH2 TRP 131 17.542 -23.029 18.517 1.00 41.50 ATOM 1239 C TRP 131 13.273 -27.560 14.873 1.00 38.05 ATOM 1240 0 TRP 131 12.439 -27.871 15.725 1.00 36.61 ATOM 1241 N LYS 132 13.346 -28.194 13.694 1.00 43.57 260

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

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ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1242 1243 1244 1245 1246 1247 1248 1249 1250 1251 1252 1253 1254 1255 1256 1257 1258 1259 1260 1261 1262 1263 1264 1265 1266 1267 1268 1269 1270 1271 1272 1273 1274 1275 1276 1277 1278 1279 1280 H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS 0 LYS N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N GLU H GLU CA GLU CE GLU CG GLU CD GLtJ OE1 GLU 0E2 GLU C GLU 0 GLU N GLY H GLY CA GLY C GLY 0 GLY N GLU 132 132 132 132 132 132 132 132 132 132 132 132 133 133 133 133 133 133 133 133 133 134 134 134 134 134 134 134 134 134 134 135 135 135 135 135 136 136 136 13.985 -27.860 12.551 -29.349 13.283 -30.640 14.216 -31.184 15.521 -30.405 16.307 -30.757 17.576 -30.049 18.153 -30.357 17.398 -29.026 18.082 -30.248 11.082 -29.544 10.526 -30.587 10.364 -28.657 10.767 -27.821 8.971 -28.915 8.743 -28.920 8.758 -30.282 7.846 -31.256 10.173 -30.854 8.011 -27.941 8.185 -26.726 6.998 -28.531 6.959 -29.504 5.955 -27.814 5.538 -28.675 4.795 -30.029 5.592 -31.292 5.830 -31.530 5.947 -32.059 4.756 -27.492 4.844 -27.559 3.620 -27.059 3.650 -26.799 2.363 -26.848 2.302 -25.664 3.004 -24.664 1.450 -25.759 0.871 -26.545 1.327 -24.710 13 .032 13.270 13 .676 12.593 12.488 11. 227 11. 211 12 .021 11. 289 10.325 13 .629 13 .267 14.311 14.621 14 .607 16.126 16.864 16.107 16.951 13 .957 13 .984 13 .340 13 .399 12 .637 11.420 11.620 11.981 13 .167 11 .081 13 .544 14.775 12 .992 12 .050 13 .724 14 .678 14.536 15.693 15.747 16 .710 1.00 0.00 1.00 47.47 1.00 48.07 1.00 49.73 1.00 53.88 1.00 55.30 1.00 57.90 1.00 0.00 1.00 0.00 1.00 0.00 1.00 49.55 1.00 53 .16 1.00 53.10 1.00 0.00 1.00 57.74 1.00 62.97 1.00 66.61 1.00 66.25 1.00 67.72 1.00 56.96 1.00 60.52 1.00 54.79 1.00 0.00 1.00 52.86 1.00 55.90 1.00 60.27 1.00 62.82 1.00 66.15 1.00 59.19 1.00 50.75 1.00 51.08 1.00 48.62 1.00 0.00 1.00 46.72 1.00 44.51 1.00 46.83 1.00 46.52 1.00 0.00 1.00 49.02

GLU

GLU

261 ATOM 1281 CB GLU 136 0.262 -25.059 17.763 1.00 51.89 15 25

A

ATOM 1282 ATOM 1283 ATOM 1284 ATOM 1285 ATOM 1286 ATOM 1287 ATOM 1288 ATOM 1289 ATOM 1290 ATOM 1291 ATOM 1292 ATOM 1293 ATOM 1294 ATOM 1295 ATOM 1296 ATOM 1297 ATOM 1298 ATOM 1299 ATOM 1300 ATOM 1301 ATOM 1302 ATOM 1303 ATOM 1304 ATOM 1305 ATOM 1306 ATOM 1307 ATOM 1308 ATOM 1309 ATOM 1310 ATOM 1311 ATOM 1312 ATOM 1313 ATOM 1314 ATOM 1315 ATOM 1316 ATOM 1317 ATOM 1318

CG

CD

OEI

OE2

C

0 GLU 136 GLU 136 GLU 136 GLU 136 GLU 136 GLU 136 ALA 137 ALA 137 ALA 137 ALA 137 ALA 137 ALA 137 LEU 138 LEU 138 LEU 138 LEU 138 LEU 138 LEU 138 LEU 138 LEU 138 LEU 138 GLU 139 0

N

H

CA

CB

CG

CD1 CD2

C

0

N

-0.931 -24.090 -0.588 -22.646 -0.616 -21.791 -0.300 -22.376 2.645 -24.489 2.944 -23.398 3.437 -25.556 3.139 -26.407 4.765 -25.477 5.442 -26.837 5.559 -24.509 6.139 -23.610 5.513 -24.597 5.012 -25.341 6.214 -23.700 5.865 -23.934 6.930 -24.048 6.191 -24.029 7.918 -22.914 5.821 -22.269 6.672 -21.402 4.526 -22.008 3.896 -22.746 4.052 -20.660 2.538 -20.665 1.945 -20.289 2.501 -21.012 3.301 -20.401 2.135 -22.162 4.587 -20.109 5.196 -19.037 4.479 -20.876 4.053 -21.755 5.037 -20.439 4.724 -21.476 3.307 -21.321 2.957 -22.366 3.103 -22.167 17.857 18.218 17.329 19.384 17.440 17.936 17.502 17.128 18.061 18.034 17.196 17.799 15.847 15.455 14 .925 13.461 12.355 11.030 12.347 15.197 15.377 15.247 15.108 15 .464 15.451 14.082 12.851 12.149 12 .583 16.760 16.774 17.839 17.765 19 .100 20.168 20.713 21.770 22.978 1.00 52.06 1.00 54.10 1.00 57.12 1.00 51.65 1.00 46.65 1.00 46.30 1.00 45.19 1.00 0.00 1.00 44.22 1.00 45.58 1.00 42.82 1.00 47.38 1.00 36.97 1.00 0.00 1.00 31.88 1.00 27.69 1.00 28.20 1.00 18.29 1.00 21.98 1.00 29.00 1.00 27.80 1.00 29.67 1.00 0.00 1.00 34.50 1.00 38.42 1.00 44.60 1.00 46.22 1.00 43 1.00 48.63 1.00 36.52 1.00 39.38 1.00 38.33 1.00 0.00 1.00 37.72 1.00 45.54 1.00 56.23 1.00 65.59 1.00 66.51 H GLU 139 CA GLU 139 CB GLU 139 CG GLU 139 CD GLU 139 OE1 GLU 139 OE2 GLU 139 C GLU 139 O GLU 139 N GLN 140 H GLN 140 CA GLN 140 CB GLN 140 CG GLN 140 CD GLN 140 ATOM 1319 OE1 GLN 140 262 ATOM 1320 NE2 GLN 140 2.480 -23.531 21.354 1.00 67.31 00% .0 .0.

S

::0.0 00000 0.0.0

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1321 1322 1323 1324 1325 1326 1327 1328 1329 1330 1331 1332 1333 1334 1335 1336 1337 1338 1339 1340 1341 1342 1343 1344 1345 1346 1347 1348 1349 1350 1351 1352 1353 1354 1355 1356 1357 1358 HE21 GLN HE22 GLN C GLN O GLN N ALA H ALA CA ALA CB ALA C ALA O ALA N ILE H ILE CA ILE CB ILE CG2 ILE CG1

CD

C

O

N

H

CA

CB

CG2 CG1

CD

C

O

N

H

CA

CB

OG

HG

C

O

N

H

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

SER

SER

SER

SER

SER

SER

SER

140 140 140 140 141 141 141 141 141 141 142 142 142 142 142 142 142 142 142 143 143 143 143 143 143 143 143 143 144 144 144 144 144 144 144 2.379 -23.670 2.259 -24.177 6.543 -20.224 7.032 -19.142 7.291 -21.155 6.848 -21.926 8.725 -21.022 9.300 -22.343 9.137 -19.872 10.287 -19.437 8.266 -19.316 7.402 -19.763 8.571 -18.125 7.449 -17.965 7.432 -16.583 7.732 -18.967 6.556 -19.269 8.660 -16.923 9.565 -16.097 7.736 -16.877 7.119 -17.638 7.613 -15.810 6.199 -15.808 5.947 -14.427 5.114 -16.077 3.812 -16.651 8.625 -16.006 9.047 -15.041 8.976 -17.255 8.616 -17.986 9.893 -17.576 9.534 -18.976 8.145 -19.030 7.612 -18.881 11.370 -17.481 12.205 -17.066 11.769 -17.860 11.133 -18.245 20.391 22.050 18.975 19.323 18.388 17.991 18.220 17.683 17.290 17.344 16.429 16.297 15.627 14.547 13.908 13.428 12.492 16.573 16.493 17.532 17.588 18.518 19.126 19.699 18.092 18.686 19.641 20.273 19.949 19.410 21.033 21.532 21.895 21.109 20.651 21.467 19.438 18.798 1.00 0.00 1.00 0.00 1.00 33.59 1.00 31.72 1.00 25.14 1.00 0.00 1.00 25.84 1.00 28.13 1.00 28.14 1.00 30.78 1.00 30.84 1.00 0.00 1.00 25.85 1.00 18.89 1.00 21.04 1.00 20.14 1.00 15.71 1.00 29.99 1.00 31.41 1.00 35.52 1.00 0.00 1.00 37.48 1.00 37.49 1.00 39.63 1.00 40.16 1.00 41.67 1.00 41.27 1.00 41.07 1.00 47.79 1.00 0.00 1.00 52.28 1.00 52.29 1.00 53.23 1.00 0.00 1.00 55.20 1.00 58.47 1.00 58.14 1.00 0.00 SER 144 GLN 145 GLN 145 263

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1359 1360 1361 1362 1363 1364 1365 1366 1367 1368 1369 1370 1371 1372 1373 1374 1375 1376 1377 1378 1379 1380 1381 1382 1383 1384 1385 1386 1387 1388 1389 1390 Hi 1391 H 1392 1393 1394 1395 1396 1397

CG

CD

0EI NE2 HE2 1 HE2 2

C

0

N

H

CA

CE

C

0

N

CD

CA

C B

CG

C

0

N

H

CA

C B

CG

C D

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

ALA

ALA

ALA

ALA

ALA

ALA

PRO

PRO

PRO

PRO

PRO

PRO

PRO

GLN

GLN

GLN

GLN

GLN

CA GLN CB GLN 145 145 145 145 145 145 145 145 145 145 146 146 146 146 146 146 147 147 147 147 147 147 147 148 148 148 148 148 148 148 148 148 148 148 148 149 149 149 149 13 .142 17. 681 13.637 -18.900 14.116 -20.105 13.040 -20.987 12.040 -20.526 13.205 -22.301 14 .014 -22.649 12.505 -22.846 13.086 -16.436 12.441 -16.418 13.761 -15.381 14.348 -15.502 13.716 -14.068 12.490 -13.332 15.014 -13.314 16.019 -13.982 15.147 -11.984 15.344 -11.200 14.760 -11.112 14-220 -9.884 15-140 -9.750 15-855 -10.796 15.560 -10.360 17.131 -11.025 17.343 -11.320 18.237 -10.822 19.609 -11.094 20.143 -10.081 19.410 -10.075 18.677 -10.999 19.566 -9.020 20.127 -8.273 19.121 -9.038 18.122 -11.771 18.647 -11.478 17.436 -12.905 17.174 -13.141 17.228 -13.855 16.571 -15.172 18.996 18.186 19.015 19.634 20. 174 19.603 19.174 20. 014 18.121 17. 066 18.584 19.358 17.955 18.513 18.266 18 .529 18 .217 19.436 17.111 17.808 18.996 16.102 14.988 16 .427 17.344 15.500 16.111 17 .095 18.428 18.795 19.207 18.912 20.078 14.327 13 .258 14.497 15 .408 13 .417 13 .960 1.0 1.0 1.0 1.0I 1.01 1.0O 1.0OC 1.00C 1.00C 1.00C 1.00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0 59.26 0 58.99 0 51.70 0 46.51 0 46.63 042.17 0.00 0.00 I59.37 I59.11 I57.86 0.00 54.83 51.86 50.12 50.90 45.39 46.16 40.33 42.32 43 .96 37.26 38.02 34.30 0 .00 29.73 33.42 38.19 44 44.63 47.86 0 .00 0.00 25 .44 25.23 23 .42 0.00 22 21 .97 OE1 GLN NE2 GLN E21 GLN E22 GLN C GLN 0 GLN N VAL H VAL CA VAL CB VAL -264 ATOM 1398 CG1 VAL 149 17.492 -15.765

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 0 ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

139! 140( 1401 1402 1403 1404 1405 1406 1407 1408 1409 1410 1411 1412 1413 1414 1415 1416 1417 1418 1419 1420 1421 1422 1423 1424 1425 1426 1427 1428 9CG2 VAL )C VAL O VAL N GLtJ H GLU CA GLU CB GLU CG GLU CD GU OE1 GLU 0E2 GLU C GLU O GLU N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS O LYS N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N ILE H ILE 149 149 149 150 150 150 150 150 150 150 150 150 150 151 151 151 151 151 151 151 151 151 151 151 151 151 152 152 152 152 152 152 152 152 152 153 153 15.220 -14.937 16.368 -13.249 16.646 -13.427 15.360 -12.455 15.224 -12.254 14.490 -11.803 13.373 -11.162 12.420 -10.140 11.567 -10.618 12.136 -11.023 10.338 -10.554 15.292 -10.801 15.156 -10.712 16.208 -10.100 16.231 -10.204 17.115 -9.138 17.760 -8.384 18.552 -7.125 18.701 -6.401 19.509 -5.113 20.920 -5.393 21.255 -6.004 21.473 -4.513 21.048 -5.890 18.127 -9.852 18.480 -9.389 18.601 -11.015 18.331 -11.332 19.524 -11.849 19-855 -13.040 21.222 -13.560 21.077 -14.775 21.866 -13.869 18.870 -12.335 19.497 -12.346 17.631 -12.796 17.208 -12.810 16.871 -13.277 15 .008 14.591 12 .309 11. 129 12 .650 13 .595 11.691 12 .511 11.875 10.706 9 .695 10.791 10.858 9 .633 11.535 12 .506 10.931 12 .094 11.791 13 .121 13 .089 12 .889 13 .662 12 .884 11.985 10.036 8 .955 10.444 11.331 9 .703 10.500 10.639 11.546 9 .301 8 .438 7.383 8 .537 9 .421 7 .392 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1 .0 1.01 1 .0O 1.0 1 OC 1.00C 1.00C 1 .00 1 .00 1 .00 1.00 1.00 1.00 1 .00 1 .00 1.00 1 .00 1.00 1 .00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 10 21.05 0 22.67 0 20.80 0 21.04 0 22.05 0 0.00 0 23.41 0 27.75 0 40.15 0 40.12 42.37 43.49 I24.41 I25.40 22.99 0.00 19.15 17.32 20.52 26.52 31.53 44.71 0.00 0.00 0 .00 16.31 12 .19 16 .09 0.00 12. 00 15.88 16.05 16 11. 67 13 .18 18.93 12 .61 0.00 18.32 ATM 1430 ATOM 1431 ATOM 1432 ATOM 1433 ATOM 1434 ATOM 1435 ATOM 1436 CA ILE 153 265 ATOM 1437 CB ILE 153 15.603 -13.925 8.013 1.00 19.63 ATOM 1438 CG2 ILE 153 14.479 -14.062 7.006 1.00 15.55 ATOM 1439 CG1 ILE 153 16.011 -15.280 8.620 1.00 20.47 ATOM 1440 CD ILE 153 16.260 -16.471 7.679 1.00 22.78 ATOM 1441 C ILE 153 16.613 -12.117 6.406 1.00 16.99 ATOM 1442 0 ILE 153 16.784 -12.260 5.192 1.00 14.84 ATOM 1443 N ALA 154 16.283 -10.929 6.906 1.00 14.59 ATOM 1444 H ALA 154 16.079 -10.868 7.864 1.00 0.00 ATOM 1445 CA ALA 154 16.129 -9.740 6.087 1.00 14.27 1 0 ATOM 1446 CB ALA 154 15.654 -8.595 6.981 1.00 11.41 ATOM 1447 C ALA 154 17.402 -9.316 5.362 1.00 13.07 ATOM 1448 0 ALA 154 17.394 -9.006 4.159 1.00 13.71 ATOM 1449 N THR 155 18.526 -9.306 6.099 1.00 12.27 ATOM 1450 H THR 155 18.467 -9.606 7.029 1.00 0.00 1 5 ATOM 1451 CA THR 155 19.830 -8.914 5 .559 1.00 10.44 *ATOM 1452 C3 THR 155 20.887 -8.906 6.713 1.00 9.80 ATOM 1453 OGi THR 155 20.456 -7.925 7.663 1.00 18.84 ATOM 1454 HG1 THR 155 19.665 -8.275 8.091 1.00 0.00 ATOM 1455 CG2 TER 155 22.278 -8.550 6.270 1.00 9.45 ATOM 1456 C THR 155 20.236 -9.883 4.440 1.00 14.92 *ATOM 1457 0 THR 155 20.778 -9.460 3 .403 1.00 15.13 ATOM 1458 N THR 156 19.900 -11.172 4.578 1.00 17.24 ATOM 1459 H THR 156 19.422 -11.506 5.372 1.00 0.00 *ATOM 1460 CA THP. 156 20.317 -12.165 3.609 1.00 17.42 25 ATOM 1461 C3 THR 156 20.778 -13.424 4.387 1.00 21.01 ATOM 1462 OG1 THR 156 19.701 -13.847 5.216 1.00 28.15 ATOM 1463 HG1 THR 156 20.090 -14.396 5.915 1.00 0.00 ATOM 1464 CG2 THR 156 22.010 -13.145 5.222 1.00 17.36 ATOM 1465 c THR 156 19.286 -12.525 2.548 1.00 16.54 ATOM 1466 0 THR 156 19.675 -13.151 1.556 1.00 16.61 ATOM 1467 N ALA 157 1,8.021 -12.082 2.648 1.00 11.96 ATOM 1468 H ALA 157 17.765 -11.593 3.460 1.00 0.00 ATOM 1469 CA ALA 157 16.978 -12.353 1.665 1.00 8.10 ATOM 1470 CB ALA 157 15.792 -11.463 1.875 1.00 5.22 ATOM 1471 C ALA 157 17.334 -12.205 0.203 1.00 11.31 ATOM 1472 0 ALA 157 16.768 -12.899 -0.628 1.00 12.82 ATOM 1473 N HIS 158 18.272 -11.321 -0.131 1.00 11.13 ATOM 1474 H HIS 158 18.588 -10.744 0.590 1.00 0.00 ATOM 1475 CA HIS 158 18.748 -11.150 -1.490 1.00 13.55 266 ATOM 1476 CB HIS 158 19.697 -9.955 -1.599 1.00 12.74 .0.

oo 00.

0000 o*

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1477 1478 1479 1480 1481 1482 1483 1484 1485 1486 1487 1488 1489 1490 1491 1492 1493 1494 1495 1496 1497 1498 1499 1500 1501 1502 1503 1504 1505 1506 F 1507 H 1508 1509 H 1510 H 1511 1512 1513 1514

CG

CD

ND

HD

CE

NE

HE

C

0

N

H

CA

CB

CG

CD

OE1 OE2

C

0

N

H

CA

CB

CG

CD

NE

HE

CZ

NHI

£Hll EH12 NH2 EH21 [H22

C

0

N

H

HIS

2 HIS '1 HIS 1 HIS 1 HIS 2 HIS 2 HIS

HIS

HIS

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

MET

MET

158 158 158 158 158 158 158 158 158 159 159 159 159 159 159 159 159 159 159 160 160 160 160 160 160 160 160 160 160 160 160 160 160 160 160 160 161 161 20.963 -9.981 22.226 -10.209 21.062 -9.767 20.371 -9.464 22.335 -9.850 23.027 -10.113 24.008 -10.028 19.481 -12.359 19.448 -12.632 20.175 -13.107 20.072 -12.955 20.940 -14.254 21.657 -14.764 22.842 -13.822 23.580 -13.832 24.583 -13.120 23.163 -14.513 20.124 -15.341 20.575 -15.957 18.879 -15.517 18.494 -14.915 18.031 -16.500 17.147 -17.180 16.251 -16.276 16.483 -16.570 15.708 -17.723 15.197 -18.221 15.689 -18.141 16.392 -17..532 16.962 -16.736 16.341 -17.882 14.895 -19.179 14.346 -19.596 14.848 -19.541 17.175 -15.879 16.168 -16.457 17.530 -14.702 18.413 -14.316 -0.760 -1.250 0.543 1.176 0. 857 -0.218 -0.233 -2.052 -3.236 -1.216 -0.257 657 -0.429 -0.229 1.103 1.190 2.045 -2.356 -3.322 -1.936 -1.266 -2.555 -1.499 -0.682 0.783 1.197 0.523 2.467 3.449 3 .244 4.384 2.743 2.018 3. 672 -3 .625 -4.043 -4.103 -3 .923 1.0 1.0 1.0 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 i. 00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0 6.21 0 5.93 0 9.66 0 0.00 7.67 9.31 0.00 I 16.19 20.47 17.23 0.00 20.55 20.24 27.41 35.05 41.39 37.57 20.03 23.76 16.92 0.00 16.29 18.52 24.37 31.61 33.80 0.00 35.13 23.68 0.00 0.00 34.48 0.00 0.00 13.93 18.72 13.50 0.00 267

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1515 1516 1517 1518 1519 1520 1521 1522 1523 1524 1525 1526 1527 1528 1529 1530 1531 1532 1533 1534 1535 1536 1537 1538 1539 1540 1541 1542 1543 1544 1545 1546 1547 1548 1549 1550 1551 1552 1553

MET

MET

MET

MET

MET

MET

MET

PRO

PRO

PRO

PRO

CG PRO C PRO 0 PRO N TRP H TRP CA TRP CB TRP CG TRP CD2 TRP CE2 TRP CE3 TRP CD1 TRP NEl TRP HEl TRP CZ2 TRP CZ3 TRP CH2 TRP C TRP 0 TRP N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR.

CEl TYR CD2 TYR CE2 TYR 161 161 161 161 161 161 161 162 162 162 162 162 162 162 163 163 163 163 163 163 163 163 163 163 163 163 163 163 163 163 164 164 164 164 164 164 164 164 164 16.690 -14.069 16.666 -12.575 15.916 -12 .130 14.135 -12.358 14.041 -13.525 17.226 -14.378 18.442 -14.348 16.412 -14.649 14.961 -14.709 16.873 -15.010 15.602 -15.227 14.600 -14.377 17.806 -14.015 18.647 -14.391 17.661 -12.733 17.016 -12.516 18.473 -11.669 17.754 -10.334 17.026 -10.040 17.590 -9.606 16.439 -9.447 18.862 -9.320 15.661 -10.145 15.341 -9.775 14.423 -9.631 16.543 -8.999 18.963. -8.873 17.808 -8.715 19.827 -11.574 20.704 -10.868 20.068 -12.259 19.506 -13.007 21.355 -12.130 21.230 -12.357 22.544 -12.125 23.138 -10.875 24.358 -10.634 23 .168 -13.149 24.392 -12.907 -5.093 -4.874 -3 .637 -3 .669 -2 .328 -6 .475 -6 .651 -7 .509 -7.458 -8.847 -9.619 -8.889 -9.519 -10.328 -9.167 -8.470 -9.712 -9.563 -8.251 -7.061 -6.263 -6 .520 -8.186 -6.971 -6.647 -4 .933 -5.184 -4.398 -9 .065 -9.562 -7.958 -7 .676 -7 .333 -5.831 -5.109 -5.204 -4 .587 -4.388 -3 .762 1.00 14.46 1.00 13.73 1.00 7.08 1.00 12.33 1.00 2.25 1.00 14.92 1.00 15.63 1.00 16.02 1.00 14.38 1.00 17 .719 1.00 17.80 1.00 17.12 1.00 19.05 1.00 21.41 1.00 19.49 1.00 0.00 1.00 14.79 1.00 16.38 1.00 15.65 1.00 18.28 1.00 16.96 1.00 14.05 1.00 11.47 1.00 13 .57 1 .00 0 .00 1.00 14.05 1.00 13 1.00 8.31 1.00 14.37 1.00 18 .36 1.00 12.49 1.00 0 .00 1.00 13 .07 1.00 12.72 1.00 10.10 1.00 13 .14 1.00 14.29 1.00 13 .03 1.00 11.06 268 ATOM 1554 CZ TYR 164 24.966 -11.647 -3.873 1.00 10.57 ATOM 1555 OH TYR 164 26.144 -11.333 -3.245 1.00 21.87 ATOM 1556 HH TYR 164 26.452 -12.073 -2.702 1.00 0.00 ATOM 1557 C TYR 164 22.208 -13.205 -7.980 1.00 18.71 ATOM 1558 0 TYR 164 21.751 -14.324 -8.226 1.00 17.75 ATOM 1559 N HIS 165 23.435 -12.870 -8.377 1.00 22.75 ATOM 1560 H HIS 165 23.729 -11.938 -8.262 1.00 0.00 ATOM 1561 CA HIS 165 24.344 -13.855 -8.923 1.00 24.59 ATOM 1562 CB HIS 165 24.598 -13.627 -10.422 1.00 23.90 1 0 ATOM 1563 CG HIS 165 23.397 -13.904 -11.315 1.00 26.19 6..*ATOM 1564 CD2 HIS 165 22.254 -13.135 -11.335 1.00 27.29 ATOM 1565 ND1 HIS 165 23.221 -14.894 -12.184 1.00 27.47 .ATOM 1566 HD1 HIS 165 23 .783 -15.675 -12.397 1.00 0.00 **ATOM 1567 CEl HIS 165 22.034 -14.736 -12 .698 1.00 25.41 1 15 ATOM 1568 NE2 HIS 165 21.456 -13.688 -12.189 1.00 21.53 ATOM 1569 HE2 HIS 165 20.486 -13 .539 -12.228 1.00 0.00 *ATOM 1570 c HIS 165 25.633 -13.656 -8.156 1.00 26.23 00.ATOM 1571 0 HIS 165 26 .362 -12.687 -8.378 1.00 31.62 ATOM 1572 N SER 166 25.946 -14.547 -7.232 1.00 25.87 ATOM 1573 H SER 166 25.362 -15.319 -7.058 1.00 0.00 ATOM 1574 CA SER 166 27.160 -14.490 -6.428 1.00 30.85 ATOM 1575 CB SER 166 27.023 -15.535 -5.320 1.00 33.11 obe:ATOM 1576 OG SER 166 26.099 -16.587 -5 .652 1.00 40.48 ATOM 1577 HG SER 166 25.779 -16.955 -4.812 1.00 0.00 ATOM 1578 c SER 166 28.485 -14.691 -7.166 1.00 32.77 ATOM 1579 0 SER 166 29 .556 -14.546 -6 .587 1.00 34.67 ATOM 1580 N SER 167 28 .439 -15.017 -8.444 1.00. 32.96 ATOM 1581 H SER 167 27.581 -15.108 -8.895 1.00 0.00 ATOM 1582 CA SER 167 29.597 -15.394 -9.219 1.00 32.24 ATOM 1583 CB SER 167 29.281 -16.777 -9 .733 1.00 35.47 ATOM 1584 OG SER 167 27.912 -16.819 -10.196 1.00 38.74 ATOM 1585 HG SER 167 27.744 -17.703 -10.543 1.00 0.00 ATOM 1586 c SER 167 30.007 -14.475 -10.363 1.00 31.65 ATOM 1587 0 SER 167 31.116 -14.603 -10.885 1.00 35.00 ATOM 1588 N LEU 168 29 .170 -13.535 -10.796 1.00 29.62 ATOM 1589 H LEU 168 28.501 -13.148 -10.198 1.00 0.00 ATOM 1590 CA LEU 168 29.473 -12.889 -12.053 1.00 29.98 ATOM 1591 CB LEU 168 28.202 -12.382 -12.708 1.00 27.12 ATOM 1592 CG LEU 168 27.207 -13.436 -13.139 1.00 23.43 269

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1593 1594 1595 1596 1597 1598 1599 1600 1601 1602 1603 1604 1605 1606 1607 1608 1609 1610 1611 1612 1613 1614 1615 1616 1617 1618 1619 1620 1621 1622 1623 1624 1625 1626 1627 1628 1629 1630 1631

H

H

H

H

CD1 LEU 168 CD2 LEU 168 C LEU 168 O LEU 168 N THR 169 H THR 169 CA THR 169 CB THR 169 OGI THR 169 HG1 THR 169 CG2 THR 169 C THR 169 0 THR 169 N ARG 170 H ARG 170 CA ARG 170 CB ARG 170 CG ARG 170 CD ARG 170 NE ARG 170 HE ARG 170 CZ ARG 170 NH1 ARG 170 iHIl ARG 170 HH12 ARG 170 NH2 ARG 170 iH21 ARG 170 1H22 ARG 170 C ARG 170 O ARG 170 N GLU 171 H GLU 171 CA GLU 171 CB GLU 171 CG GLU 171 CD GLU 171 OE1 GLU 171 OE2 GLU 171 C GLU 171 26.136 -12.746 27.873 -14.525 30.445 -11.753 30.379 -10.917 31.400 -11.777 31.509 -12.555 32.276 -10.639 33.596 -11.055 33.258 -11.649 34.045 -12.124 34.415 -12.014 31.478 -9.695 30.372 -10.044 32.041 -8.525 32.861 -8.261 31.421 -7.557 32.320 -6.316 31.766 -5.288 32.742 -4.160 32.560 -3.097 32.924 -3.206 31.948 -1.951 31.809 -1.036 32.161 -1.213 31.349 -0.170 31.505 -1.660 31.615 -2.316 31.055 -0.783 31.201 -8.165 30.132 -8.046 32.220 -8.866 32.978 -8.985 32.195 -9.477 33.580 -10.054 34.771 -10.040 35.272 -8.696 35.099 -7.641 35.845 -8.717 31.154 -10.579 -13.947 -13.992 -11.974 -11.074 -12.898 -13.479 -13 .076 -13 .767 -15.020 -15.328 -12.917 -13 .973 -14.417 -14.294 -13.824 -15.199 -15.323 -16.289 -16.541 -15 .587 -14.684 -15.896 -14.946 -14.027 -15 .144 -17.112 -17.858 -17.278 -16.577 -17.178 -17.047 -16.448 -18.364 -18.735 -17 .736 -17.177 -17.803 -16.084 -18.416 1.00 23.27 1.00 22.89 1.00 32.36 1.00 36.48 1.00 31.71 1.00 0.00 1.00 30.85 1.00 32.01 1.00 34.34 1.00 0.00 1.00 33.00 1.00 29.05 1.00 26.29 1.00 30.94 1.00 0.00 1.00 27.92 1.00 25.77 1.00 22.36 1.00 21.88 1.00 23.01 1.00 0.00 1.00 26.69 1.00 32.94 1.00 0.00 1.00 0.00 1.00 25.12 1.00 0.00 1.00 0.00 1.00 25.49 1.00 28.82 1.00 25.45 1.00 0.00 1.00 28.63 1.00 34.71 1.00 46.27 1.00 49.62 1.00 49.52 1.00 52.83 1.00 24.95 270

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1632 1633 1634 1635 1636 1637 1638 1639 1640 1641 1642 1643 1644 1645 1646 1647 1648 1649 1650 1651 1652 1653 1654 1655 1656 1657 1658 1659 1660 1661 1662 1663 1664 1665 1666 1667 1668 1669 F 1670 F 0

N

H

CA

CB

CG

CD

OEI

OE2

C

0

N

H

CA

CE

C

0

N

H

CA

CB

CG

CD

OEI

OE2

C

0

N

H

CA

CB

CG

CD

NE

HE

CZ

NH1 HI1 H12 GLU 171 GLU 172 GLU 172 GLU 172 GLU 172 GLU 172 GLU 172 GLU 172 GLU 172 GLU 172 GLU 172 ALA 173 ALA 173 ALA 173 ALA 173 ALA 173 ALA 173 GLU 174 GLU 174 GLU 174 GLU 174 GLU 174 GLU 174 GLU 174 GLU 174 GLU 174 GLU 174 ARG 175 ARG 175 ARG 175 ARG 175 ARG 175 ARG 175 ARG 175 ARG 175 ARG 175 ARG 175 ARG 175 ARG 175 30.279 31.181 31.828 30.210 30.508 31.858 32.251 32.039 32.785 28.797 27.888 28.592 29.348 27.280 27.311 26.819 25.661 27.695 28.605 27.350 28.531 28.706 29.944 31.017 29.824 26.919 25.868 27.699 28.513 27.374 28.389 29.859 30.745 32.019 32.252 32.890 32.656 31.812 33.332 -10.593 -19.294 -11.445 -17.405 -11.331 -16.679 -12.516 -17.343 -13.429 -16.192 -14.079 -16.392 -15.088 -15.337 -14.841 -14.149 -16.129 -15.716 -12.006 -17.199 -12.558 -17.827 -10.941 -16.416 -10.540 -15.948 -10.335 -16.264 -9.190 -15.242 -9.766 -17.598 -9.963 -17.977 -9.077 -18.346 -8.964 -18.004 -8.542 -19.663 -7.822 -20.244 -6.545 -19.477 -5.776 -19.873 -6.383 -20.010 -4.560 -20.021 -9.632 -20.632 -9.544 -21.276 -10.711 -20.690 -10.712 -20.144 -11.870 -21.517 -12.991 -21.253 -12.688 -21.529 -13.832 -21.022 -13.336 -20.499 -12.393 -20.637 -14.117 -19.832 -15.414 -19.599 15.837 -19.926 15.959 -19.102 1.00 23.81 1.00 22.24 1.00 0.00 1.00 24.18 1.00 27.98 1.00 32.11 1.00 37.30 1.00 41.49 1.00 45.22 1.00 26.45 1.00 32.90 1.00 25.95 1.00 0.00 1.00 23.01 1.00 20.11 1.00 23.39 1.00 25.28 1.00 24.22 1.00 0.00 1.00 25.70 1.00 21.46 1.00 24.32 1.00 31.18 1.00 37.96 1.00 30.27 1.00 26.95 1.00 27.65 1.00 30.32 1.00 0.00 1.00 32.32 1.00 37.30 1.00 45.49 1.00 51.37 1.00 55.15 1.00 0.00 1.00 59.00 1.00 58.66 1.00 0.00 1.00 0.00 271 ATOM 1671 NH2 ARG 175 0 oo* o o 9

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1672 1673 1674 1675 1676 1677 1678 1679 1680 1681 1682 1683 1684 1685 1686 1687 1688 1689 1690 1691 1692 1693 1694 1695 1696 1697 1698 1699 1700 1701 1702 1703 1704 1705 1706 1707 1708 1709 HH21 ARG HH22 ARG C ARG O ARG N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS O LYS N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU 0 LEU N TYR H TYR CA TYR CB TYR CG TYR 175 175 175 175 176 176 176 176 176 176 176 176 176 176 176 176 176 177 177 177 177 177 177 177 177 177 178 178 178 178 178 178 178 178 178 178 178 178 34.024 -13.588 -19.361 34.213 -12.616 -19.502 34.681 -14.160 -18.872 25.963 -12.388 -21.213 25.110 -12.551 -22.088 25.702 -12.560 -19.921 26.414 -12.342 -19.277 24.452 -13.071 -19.401 24.531 -13.145 -17.892 23.547 -14.115 -17.250 24.055 -15.547 -17.412 25.324 -15.720 -16.575 25.941 -17.022 -16.754 26.298 -17.096 -17.728 25.235 -17.766 -16.585 26.728 -17.135 -16.083 23.285 -12.195 -19.791 22.269 -12.672 -20.284 23.436 -10.892 -19.595 24.296 -10.569 -19.251 22.383 -9.922 -19.855 22.814 -8.567 -19.282 22.271 -7.948 -17.963 21.559 -8.933 -17.048 23.468 -7.352 -17.267 22.080 -9.800 -21.333 20.930 -9.592 -21.719 23.085 -9.914 -22.199 23.995 -10.079 -21.869 22.838 -9.805 -23.628 24.156 -9.530 -24.341 24.568 -8.071 -24.223 23.631 -7.081 -24.509 23.995 -5.745 -24.396 25.867 -7.715 -23.825 26.232 -6.366 -23.709 25.282 -5.387 -23.999 25.580 -4.043 -23.874 25.002 -3.585 -24.505 i.00 61.91 1.00 0.00 1.00 0.00 1.00 30.27 1.00 32.04 i.00 32.42 1.00 0.00 i.00 32.03 1.00 35.56 !.00 44.13 1.00 48.57 1.00 52.52 1.00 52.83 00 0.00 !.00 0.00 1.00 0.00 1.00 31.06 1.00 31.58 1.00 34.11 .00 0.00 1.00 32.25 1.00 30.73 1.00 31.54 1.00 26.77 1.00 24.48 1.00 32 1.00 34.39 >.00 34.48 1.00 0.00 .00 36.68 1.00 35.30 1.00 31.08 1.00 30.05 1.00 30.73 1.00 29.53 1.00 26.18 1.00 25.96 1.00 25.36 i.00 0.00 CD1

CEI

CD2 CE2 Cz

OH

HH

TYR

TYR

TYR

TYR

TYR

TYR

TYR

272 ATOM 1710 C TYR 178 22.172 -11.038 -24.219 1.00 38.35 ATOM 1711 0 TYR 178 21.576 -11.020 -25.307 1.00 37.60 ATOM 1712 N SER 179 22.300 -12.135 -23.481 1.00 40.20 ATOM 1713 H SER 179 22.747 -12.098 -22.611 1.00 0.00 ATOM 1714 CA SER 179 21.693 -13.366 -23.885 1.00 40.95 ATOM 1715 CB SER 179 22.147 -14.488 -22.964 1.00 38.18 ATOM 1716 OG SER 179 23.552 -14.693 -23.097 1.00 42.54 ATOM 1717 HG SER 179 24.014 -13.865 -22.917 1.00 0.00 ATOM 1718 C SER 179 20.181 -13.236 -23.859 1.00 44.69 1 0 ATOM 1719 0 SER 179 19.507 -12.850 -22.897 1.00 43.01 ATOM 1720 N GLY 180 19.685 -13.487 -25.059 1.00 49.23 ATOM 1721 H GLY 180 20.289 -13.525 -25.832 1.00 0.00 ATOM 1722 CA GLY 180 18.273 -13.576 -25.269 1.00 50.39 ATOM 1723 C GLY 180 17.657 -12.238 -25.579 1.00 53.13 1 5 ATOM 1724 0 GLY 180 18.179 -11.405 -26.325 1.00 52.03 ATOM 1725 N ALA 181 16.551 -12.099 -24.852 1.00 55.03 ATOM 1726 H ALA 181 16.426 -12.708 -24.086 1.00 0.00 ATOM 1727 CA ALA 181 15.575 -11.041 -25.034 1.00 54.94 ATOM 1728 CB ALA 181 14.436 -11.279 -24.044 1.00 56.02 00.0 20 ATOM 1729 C ALA 181 16.003 -9.584 -24.928 1.00 54.22 o o•go ATOM 1730 o ALA 181 15.448 -8.741 -25.638 1.00 56.20 ATOM 1731 N GLN 182 16.947 -9.267 -24.032 1.00 49.18 ATOM 1732 H GLN 182 17.366 -9.999 -23.535 1.00 0.00 ATOM 1733 CA GLN 182 17.430 -7.908 -23.794 1.00 44.29 25 ATOM 1734 CB GLN 182 18.314 -7.462 -24.967 1.00 41.96 oo~oo: o ATOM 1735 CG GLN 182 19.551 -8.314 -25.058 1.00 41.18 ATOM 1736 CD GLN 182 20.483 -7.844 -26.148 1.00 44.47 ATOM 1737 OE1 GLN 182 20.784 -6.664 -26.295 1.00 48.23 ATOM 1738 NE2 GLN 182 21.012 -8.740 -26.949 1.00 50.67 ATOM 1739 HE21 GLN 182 20.793 -9.686 -26.786 1.00 0.00 ATOM 1740 HE22 GLN 182 21.587 -8.410 -27.662 1.00 0.00 ATOM 1741 C GLN 182 16.324 -6.875 -23.552 1.00 40.00 ATOM 1742 0 GLN 182 16.323 -5.731 -24.026 1.00 41.01 ATOM 1743 N THR 183 15.365 -7.291 -22.735 1.00 35.70 ATOM 1744 H THR 183 15.390 -8.208 -22.393 1.00 0.00 ATOM 1745 CA THR 183 14.255 -6.456 -22.308 1.00 33.60 ATOM 1746 CB THR 183 13.298 -7.378 -21.503 1.00 36.83 ATOM 1747 OGI THR 183 13.223 -8.626 -22.202 1.00 40.13 ATOM 1748 HG1 THR 183 12.742 -8.509 -23.029 1.00 0.00 273 ATOM 1749 CG2 THR 183 ATOM 174 CG2THR 18311.906 -6.789 -21.348 1.00 38.03 ATOM 1750 C THR 183 14.790 -5.271 -21.471 1.00 32.43 ATOM 1751 0 THR 183 15.797 -5.393 -20.764 1.00 30.96 ATOM 1752 N ASP 184 14.166 -4.091 -21.553 1.00 30.47 ATOM 1753 H ASP 184 13.379 -4.025 -22.126 1.00 0.00 ATOM 1754 CA ASP 184 14.538 -2.916 -20.779 1.00 28.11 ATOM 1755 CB ASP 184 13.670 -1.722 -21.181 1.00 28.38 -1 56 CG ASP 184 14.010 -0.944 -22.457 1.00 32.30 ATOM 1757 ODI ASP 184 13.124 -0.235 -22.959 1.00 29.32 1 0 ATOM 1758 0D2 ASP 184 15.144 -1.024 -22.938 1.00 30.40 ATOM 1759. C ASP 184 14.336 -3.192 -19.285 1.00 26.83 ATOM 1760 0 ASP 184 13.322 -3.777 -18.894 1.00 24.72 ATOM 1761 N GLY 185 15.294 -2.826 -18.441 1.00 25.09 ***ATOM 1762 H GLY 185 16.080 -2.372 -18.798 1.00 0.00 1 5 ATOM 1763 CA GLY 185 15.206 -3.060 -17.010 1.00 25.19 ATOM 1764 C GLY 185 15.537 -4.484 -16.606 1.00 20.65 ATOM 1765 0 GLY 185 15.341 -4.837 -15.450 1.00 20.02 :::ATOM 1766 N LYS 186 16.048 -5.333 -17.498 1.00 21.61 ATOM 1767 H LYS 186 16.285 -4.995 -18.386 1.00 0.00 ATOM 1768 CA LYS 186 16.388 -6.706 -17.155 1.00 21.03 ATOM 1769 CB LYS 186 16.592 -7.514 -18.405 1.00 22.81 ATOM 1770 CG LYS 186 17.021 -8.954 -18.261 1.00 23.15 .ATOM 1771 CD LYS 186 17.304 -9.312 -19.716 1.00 24.01 ATOM 1772 CE LYS 186 18.073 -10.597 -19.860 1.00 25.57 ATOM 1773 NZ LYS 186 18.360 -10.834 -21.258 1.00 26.92 *.ATOM 1774 HZ1 LYS 186 18.897 -10.028 -21.638 1.00 0.00 *99.ATOM 1775 HZ2 LYS 186 17.473 -10.945 -21.789 1.00 0.00 ATOM 1776 HZ3 LYS 186 18.932 -11.698 -21.346 1.00 0.00 ATOM 1777 c LYS 186 17.678 -6.569 -16.401 1.00 20.18 ATOM 1778 0 LYS 186 18.632 -5.993 -16.932 1.00 22.74 ATOM 1779 N PHE 187 17.736 -7.127 -15.209 1.00 18.17 ATOM 1780 H PHE 187 17.018 -7.724 -14.905 1.00 0.00 ATOM 1781 CA PHE 187 18.835 -6.825 -14.323 1.00 15.32 ATOM 1782 CB PHE 187 18.343 -5.741 -13.341 1.00 13.75 ATOM 1783 CG PHE 187 17.375 -6.215 -12.254 1.00 10.60 ATOM 1784 CD1 PHE 187 17.851 -6.516 -10.963 1.00 4.59 ATOM 1785 CD2 PHE 187 16.027 -6.375 -12.550 1.00 6.32 ATOM 1786 CEl PHE 187 16.975 -6.978 -10.000 1.00 3.69 ATOM 1787 CE2 PHE 187 15.161 -6.840 -11.564 1.00 8.44 274 ATOM 1788 CZ PHE 187 15.630 -7.146 -10.294 1.00 5.46 ATOM 1789 C PHE 187 19.404 -7.979 -13.538 1.00 12.65 ATOM 1790 0 PHE 187 18.770 -9.031 -13.434 1.00 19.75 ATOM 1791 N LEU 188 20.550 -7.750 -12.906 1.00 11.33 ATOM 1792 H LEU 188 21.054 -6.926 -13.096 1.00 0.00 ATOM 1793 CA LEU 188 21.065 -8.647 -11.899 1.00 11.79 ATOM 1794 CB LEU 188 21.938 -9.744 -12.521 1.00 15.47 ATOM 1795 CG LEU 188 23.210 -9.476 -13.324 1.00 15.83 ATOM 1796 CD1 LEU 188 24.466 -9.304 -12.465 1.00 8.89 1 0 ATOM 1797 CD2 LEU 188 23.364 -10.695 -14.223 1.00 13.24 ATOM 1798 C LEU 188 21.892 -7.837 -10.908 1.00 13.76 ATOM 1799 0 LEU 188 22.306 -6.706 -11.206 1.00 9.67 ATOM 1800 N LEU 189 22.156 -8.386 -9.726 1.00 11.91 ATOM 1801 H LEU 189 21.844 -9.295 -9.525 1.00 0.00 1 5 ATOM 1802 CA LEU 189 23.002 -7.720 -8.770 1.00 11.04 o *o ATOM 1803 CB LEU 189 22.139 -7.371 -7.533 1.00 10.60 ATOM 1804 CG LEU 189 22.718 -6.409 -6.467 1.00 10.76 ATOM 1805 CD1 LEU 189 21.591 -5.775 -5.699 1.00 16.31 ATOM 1806 CD2 LEU 189 23.580 -7.144 -5.462 1.00 11.36 20 ATOM 1807 C LEU 189 24.090 -8.751 -8.511 1.00 10.52 .o ATOM 1808 0 LEU 189 23.821 -9.956 -8.487 1.00 15.16 ATOM 1809 N ARG 190 25.335 -8.355 -8.354 1.00 9.93 ATOM 1810 H ARG 190 25.548 -7.398 -8.329 1.00 0.00 ATOM 1811 CA ARG 190 26.417 -9.296 -8.148 1.00 15.26 ATOM 1812 CB ARG 190 27.158 -9.565 -9.487 1.00 19.74 ATOM 1813 CG ARG 190 27.523 -8.309 -10.276 1.00 18.73 ATOM 1814 CD ARG 190 28.210 -8.529 -11.615 1.00 19.13 ATOM 1815 NE ARG 190 28.258 -7.264 -12.327 1.00 15.71 ATOM 1816 HE ARG 190 27.488 -7.013 -12.880 1.00 0.00 ATOM 1817 CZ ARG 190 29.300 -6.427 -12.264 1.00 12.44 ATOM 1818 NH1 ARG 190 30.398 -6.661 -11.557 1.00 12.24 ATOM 1819 HH11 ARG 190 30.484 -7.501 -11.020 1.00 0.00 ATOM 1820 HH12 ARG 190 31.138 -5.988 -11.551 1.00 0.00 ATOM 1821 NH2 ARG 190 29.204 -5.265 -12.874 1.00 19.14 ATOM 1822 HH21 ARG 190 28.357 -5.038 -13.349 1.00 0.00 ATOM 1823 HH22 ARG 190 29.953 -4.608 -12.846 1.00 0.00 ATOM 1824 C ARG 190 27.363 -8.675 -7.128 1.00 17.85 ATOM 1825 0 ARG 190 27.428 -7.441 -7.051 1.00 17.12 ATOM 1826 N PRO 191 28.063 -9.426 -6.269 1.00 19.25 275 ATOM 1827 CD PRO 191 27.823 -10.832 -593 10 1.6 -5.993 1.00 15.67 ATOM 1828 CA PRO 191 29.087 -8.896 -5.386 1.00 18.77 ATOM 1829 CB PRO 191 29.348 -9.996 -4.377 1.00 17.25 ATOM 1830 CG PRO 191 29.015 -11.250 -5.129 1.00 13.46 ATOM 1831 C PRO 191 30.314 -8.517 -6.174 1.00 22.81 ATOM 1832 0 PRO 191 30.605 -9.074 -7.241 1.00 22.89 ATOM 1833 N ARG 192 31.057 -7.551 -5.672 1.00 25.23 ATOM 1834 H ARG 192 30.882 -7.165 -4.790 1.00 0.00 ATOM 1835 CA ARG 192 32.254 -7.192 -6.372 1.00 27.78 ATOM 1836 CB ARG 192 32.321 -5.708 -6.573 1.00 23.97 ATOM 1837 CG ARG 192 31.329 -5.258 -7.639 1.00 20.97 ATOM 1838 CD ARG 192 31.708 -3.925 -8.249 1.00 21.89 ATOM 1839 NE ARG 192 32.301 -3.053 -7.259 1.00 29.17 ATOM 1840 HE ARG 192 31.803 -2.865 -6.436 1.00 0.00 1 5 ATOM 1841 CZ ARG 192 33.503 -2.487 -7.403 1.00 33.01 .0.ATOM 1842 NH1I ARG 192 34.277 -2.657 -8.478 1.00 27.14 *ATOM 1843 HH11 ARG 192 33.966 -3.223 -9.241 1.00 0.00 *ATOM 1844 HH112 ARG 192 35.166 -2.200 -8.525 1.00 0.00 ATOM 1845 NH2 ARG 192 33.960 -1.776 -6.376 1.00 40.84 ATOM 1846 HH21 ARG 192 33.406 -1.692 -5.548 1.00 0.00 ATOM 1847 HH22 ARG 192 34.853 -1.330 -6.427 1.00 0.00 ATOM 1848 c ARG 192 33.425 -7.668 -5.557 1.00 34.57 *.ATOM 1849 0 ARG 192 33.324 -7.845 -4.339 1.00 37.12 ATOM 1850 N LYS 193 34.526 -7.881 -6.289 1.00 42.26 ATOM 1851 H LYS 193 34.467 -7.655 -7 .245 1.00 0.00 ATOM 1852 CA LYS 193 35.795 -8.403 -5.795 1.00 47.15 ATOM 1853 CB LYS 193 36.904 -8.081 -6.793 1.00 52.06 ATOM 1854 CG LYS 193 36.997 -8.876 -8.091 1.00 54.92 ATOM 1855 CD LYS 193 38.281 -8.541 -8.878 1.00 55.99 ATOM 1856 CE LYS 193 39.618 -8.936 -8.217 1.00 58.17 ATOM 1857 NZ LYS 193 40.052 -8.033 -7.156 1.00 59.70 ATOM 1858 HZ1 LYS 193 39.351 -8.030 -6.388 1.00 0.00 ATOM 1859 HZ2 LYS 193 40.147 -7.069 -7.537 1.00 0.00 ATOM 1860 HZ3 LYS 193 40.973 -8.345 -6.784 1.00 0.00 ATOM 1861 C LYS 193 36.264 -7.923 -4.427 1.00 48.59 ATOM 1862 0 LYS 193 36.714 -8.701 -3 .585 1.00 48.16 ATOM 1863 N GU 194 36.139 -6.621 -4.202 1.00 48.68 ATOM 1864 H GLU 194 35.613 -6.112 -4.842 1.00 0.00 ATOM 1865 CA GLU 194 36.536 -5.982 -2.962 1.00 52.35 276 ATOM 1866 CB GLU 194

ATOM

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ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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1867 CG GLU 1868 CD GLU 1869 OE1 GLU 1870 0E2 GLU 1871 C GLU 1872 0 GLU 1873 N GLN 1874 H GLN 1875 CA GLN 1876 CB GLN 1877 CG GLN 1878 CD GLN 1879 0E1 GLN 1880 NE2 GLN 1881 HE21 GLN 1882 HE22 GLN 1883 C GLN 1884 0 GLN 1885 N GLY 1886 H GLY 1887 CA GLY 1888 C GLY 1889 0 GLY 1890 N THR 1891 H THR 1892 CA THR 1893 CB THR 1894 OGi THR 1895 HG1 THR 1896 CG2 THR 1897 c THR 1898 0 THR 1899 N TYR 1900 H TYR 1901 CA TYR 1902 CB TYR 1903 CG TYR 1904 CD1 TYR 194 194 194 194 194 194 195 195 195 195 195 195 195 195 195 195 195 195 196 196 196 196 196 197 197 197 197 197 197 197 197 197 198 198 198 198 198 198 36.997 -4.537 -3.272 1.00 55.36 36.171 -3.649 -4.234 1.00 57.27 36.365 -3.891 -5.731 1.00 56.04 37.277 -3.298 -6.310 1.00 56.94 35.595 -4.652 -6.319 1.00 54.29 35.267 -6.045 -2.121 1.00 52.06 34.474 -5.109 -2.048 1.00 51.19 35.081 -7.232 -1.545 1.00 54.38 35.805 -7.885 -1.636 1.00 0.00 33.858 -7.619 -0.850 1.00 55.92 34.139 -8.895 -0.051 1.00 59.23 34.284 -10.113 -0.980 1.00 61.52 33.058 -10.451 830 1.00 63.22 31.897 -10.254 -1.457 1.00 66.50 33 .269 -11.005 -3.011 1.00 64.00 34.194 -11.170 -3 .287 1.00 0.00 32.482 -11.228 -3 .547 1.00 0.00 33.171 -6.599 0.039 1.00 52.83 33.784 -5.715 0.646 1.00 54.52 31.851 -6.727 0.086 1.00 48.51 31.410 -7.490 -0.347 1.00 0.00 31.058 -5.704 0.734 1.00 43.01 30.677 -4.644 -0.298 1.00 38.41 29.901 -3.742 0 .029 1.00 39.57 31.232 -4.650 524 1.00 34.03 31.954 -5.266 -1.758 1.00 0.00 30.740 -3 .783 -2.574 1.00 26.80 31.858 -3.075 -3 .375 1.00 27.15 32.759 -4.048 -3 .873 1.00 29.46 33 .343 -4.272 -3 .145 1.00 0.00 32.554 -2.032 -2.514 1.00 27.29 29.972 -4.717 -3 .498 1.00 24.98 30.181 -5.945 -3 .493 1.00 23 29.030 -4.130 -4.243 1.00 21.47 28.957 -3.149 -4.246 1.00 0.00 28.129 -4.849 -5.118 1.00 18.56 26.753 -5.073 -4.426 1.00 12.78 26.823 -5.927 -3 .146 1.00 22.01 27.142 -5.362 -1.895 1.00 20.02 277 ATOM 1905 CE1 TYR 198 ATOM 190 C~lTYR 198 27.264 -6.166 -0.747 1.00 22.60

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1906 1907 1908 1909 1910 1911 1 97 12 1913 1914 1915 1916 1917 1918 1919 1920 1921 1922 1923 1924 1925 1926 1927 1928 1929 1930 1931 1932 1933 1934 1935 1936 1937 1938 1939 1940 1941 1942 1943 CD2 TYR 198 CE2 TYR 198 CZ TYR 198 OH TYR 198 HH TYR 198 C TYR 198 o TY R 198 N ALA 199 H ALA 199 CA ALA 199 CB ALA 199 C ALA 199 O ALA 199 N LEU 200 H LEU 200 CA LEU 200 CB LEU 200 CG LEU 200 CD1 LEU 200 CD2 LEU 200 C LEU 200 O LEU 200 N SER 201 H SER 201 CA SER 20.31 CB SER 201 OG SER 201 HG SER 201 C SER 201 O SER 201 N LEU 202 H LEU 202 CA LEU 202 CE LEU 202 CG LEU 202 CD1 LELI 202 CD2 LEU 202 C LEU 20 26.618 26.741 27.065 27.201 27.735 27.965 28.322 27.514 27.340 27.203 28.194 25.877 25.602 25.047 25.351 23 .747 22.780 21.249 20.765 20.710 23.964 24.416 23.746 23.328 23 .939 24.899 26.098 25.836 22.594 21.864 22.194 22.784 20.906 19.826 19.923 18.554 20.906 20.997 -7.306 -3.214 -8.114 -2.071 -7.544 -0.837 -8.359 0.286 -9.132 0.008 -3.975 -6.365 -2.782 -6.377 -4.574 -7.465 -5.539 -7.472 -3.802 -8.639 -4.003 -9.768 -4.356 -9.092 -5.564 -8.991 -3.427 -9.530 -2.496 -9.531 -3.719 -10.080 -2.719 -9.450 -2.769 -9.466 -1.518 -10.193 -4.042 -10.105 -3.527 -11.591 -2.467 -12.025.

-4.526 -12.434 -5.350 -12.112 -4.381 -13.867 -5.455 -14.323 -5.406 -13.557 -5.633 -12.651 -4.535 -14.549 -5.452 -14.163 -3.704 -15.513 -2.981 -15.814 -3.879 -16.184 -2.932 -15.635 -1.415 -15.745 -0.802 -15.515 -0.888 -14.726 -3.636 -17.679 1.00 19.95 1.00 25.51 1.00 23.70 1.00 31.49 1.00 0.00 1.00 21.17 1.00 18.78 1.00 17.77 1.00 0.00 1.00 17.47 1.00 16.18 1.00 18.13 1.00 22.08 1.00 14.97 1.00 0.00 1.00 17.06 1.00 12.56 1.00 21.69 1.00 17.31 1.00 16.41 1.00 15.53 1.00 11.97 1.00 17.37 1.00 0.00 1.00 18.19 1.00 15.29 1.00 13.30 1.00 0.00 1.00 16.35 1.00 17.51 1.00 20.48 1.00 0.00 1.00 20.46 1.00 19.55 1.00 20.47 1.00 26.80 1.00 24.17 1.00 24.32 278 ATOM 1944 0 LEU 202 ATOM 1944 0 LE 20222.026 -3.156 -18.168 1.00 22.66 a.

a a a a a a a a a. a a a a 1 5 20 25 ATOM 1945 ATOM 1946 ATOM 1947 ATOM 1948 ATOM 1949 ATOM 1950 ATOM 1951 ATOM 1952 ATOM 1953 ATOM 1954 ATOM 1955 ATOM 1956 ATOM 1957 ATOM 1958 ATOM 1959 ATOM 1960 ATOM 1961 ATOM 1962 ATOM 1963 ATOM 1964 ATOM 1965 ATOM 1966 ATOM 1967 ATOM 1968 ATOM 1969 ATOM 1970 ATOM 1971 ATOM .1972 ATOM 1973 ATOM 1974 ATOM 1975 ATOM 1976 ATOM 1977 ATOM 1978 ATOM 1979 ATOM 1980 ATOM 1981 ATOM 1982

H

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GLY

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203 203 203 203 203 203 203 203 203 204 204 204 204 204 204 204 204 204 204 204 204 204 204 205 205 205 205 205 206 206 206 206 206 206 206 206 206 206 19.929 19.187 19.801 19.185 18.668 20.225 21. 302 18.902 17.835 19.326 20.252 18.505 18.691 17.817 16.435 15.613 18.389 17 .566 16.189 15.364 15.823 18.951 20.108 18.035 17 .167 18.331 19.445 20.434 19.310 18.469 20.310 20.348 19.208 19.427 18.857 17.414 17.100 16.942 -3.998 -18.393 -4.430 -17.925 -3.775 -19.817 -5.025 -20.488 -4.683 -21.880 -6.114 -20.595 -5.877 -21.688 -2.567 -20.030 -2.440 -19.411 -1.667 -20.901 -1.690 -21.219 -0.566 -21.310 0.638 -20.392 1.779 -20.871 1.597 -20.888 2.589 -21.400 2.952 -21.353 3.946 -21.872 3.749 -21.888 4.701 -22.428 5.551 -22.421 -0.202 -22.712 0.141 -22.948 -0.296 -23.672 -0.691 -23.456 0.022 -25.063 -0.886 -25.568 -0.425 -26.129 -2.183 -25.274 -2.463 -24.853 -3.204 -25.576 -3.437 -27.106 -4.284 -27.668 -4.533 -29.171 -5.858 -29.733 -5.981 -29.599 -6.871 -30.034 -5.181 -30.067 1.00 25.50 1.00 0.00 1.00 23.41 1.00 24.34 1.00 29.27 1.00 20.19 1.00 27.26 1.00 24.65 1.00 26.06 1.00 23.00 1.00 0.00 1.00 22.39 1.00 23.53 1.00 19.38 1.00 21.27 1.00 23.27 1.00 17.37 1.00 20.74 1.00 22.21 1.00 35.35 1.00 0.00 1.00 24.33 1.00 23.64 1.00 27.09 1.00 0.00 1.00 28.04 1.00 28.26 1.00 29.56 1.00 30.20 1.00 0.00 1.00 30.88 1.00 39.67 1.00 46.40 1.00 58.59 1.00 59.73 1.00 60.63 1.00 0.00 1.00 0.00 H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS -279 ATOM 1983 HZ3 LYS 206 ATM 98 Z3LY 26 17.164 -5.984 -28.588 1.00 0.00 1 5 9

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@0 5 0000 5* 0 0 ATOM 1984 ATOM 1985 ATOM 1986 ATOM 1987 ATOM 1988 ATOM 1989 ATOM 1990 ATOM 1991 ATOM 1992 ATOM 1993 ATOM 1994 ATOM 1995 ATOM 1996 ATOM 1997 ATOM 1998 ATOM 1999 ATOM 2000 ATOM 2001 ATOM 2002 ATOM 2003 ATOM 2004 ATOM 2005 ATOM 2006 ATOM 2007 ATOM 2008 ATOM 2009 ATOM 2010 ATOM 2011 ATOM 2012 ATOM 2013 ATOM 2014 ATOM 2015 ATOM 2016 ATOM 2017 ATOM 2018 ATOM 2019 ATOM 2020 ATOM 2021 C LYS 206 O LYS 206 N THR 207 H THR 207 CA THR 207 CB THR 207 OGi THR 207 HG1 THR 207 CG2 THR 207 C THR 207 O THR 207 N VAL 208 H VAL 208 CA VAL 208 CB VAL 208 CG1 VAL 208 CG2 VAL 208 C VAL 208 O VAL 208 N TYR 209 H TYR 209 CA TYR 209 CB TYR 209 CG TYR 209 CD1 TYR 209 CE1 TYR 209 CD2 TYR 209 CE2 TYR 209 CZ TYR 209 OH TYR 209 HH TYR 209 C TYR 209 O TYR 209 N HIS 210 H HIS 210 CA HIS 210 CB HIS 210 CG HIS 210 21.713 22.715 21.854 21. 093 23 .157 23 .513 23.486 22 .576 24. 897 23.126 22.104 24.243 24.986 24.418 25.352 25.598 24.688 25.030 26.021 24.398 23 .600 24.819 23 .703 23.419 24.275 24.025 22 .293 22.033 22.899 22.636 22 .811 25.151 24 .410 26.256 26.826 26.609 28.008 28.135 -2.885 -25.048 -3.453 -25.484 -1.988 -24.075 -1.475 -23.736 -1.686 -23.497 -0.193 -23.705 0.043 -25.101 -0.039 -25.421 0.172 -23.191 -2.009 -22.006 -1.825 -21.322 -2.586 -21.544 -2.778 -22.157 -2.923 -20.146 -4.142 -19.988 -4.433 -18.520 5.371 -20.555 -1.705 -19.479 -1.153 -19.973 -1.315 -18.369 -1.825 -18.102 -0.206 -17.528 0.788 -17.413 1.508 -18.712 2.526 -19.114 3.264 -20.261 1.197 -19.473 1.929 -20.630 2.958 -21.010 3.699 -22.143 4.641 -21.974 -0.751 -16.144 -1.594 -15.633 -0.371 -15.515 0.337 -15.894 -0.918 -14.218 -1.531 -14.215 -2.724 -15.153 1.00 27.65 1.00 26.71 1.00 27.08 1.00 0.00 1.00 29.48 1.00 26.97 1.00 30.98 1.00 0.00 1.00 21.13 1.00 31.62 1.00 29.33 1.00 32.82 1.00 0.00 1.00 27.75 1.00 26.11 1.00 25.10 1.00 21.70 1.00 26.14 1.00 24.51 1.00 24.22 1.00 0.00 1.00 20.40 1.00 21.23 1.00 25.834 1.00 27.02 1.00 30.87 1.00 25.74 1.00 33 .37 1.00 34.59 1.00 43.26 1.00 0.00 1.00 18.17 1.00 17.18 1.00 17.72 1.00 0.00 1.00 19.24 1.00 21.16 1.00 23.97 280 ATOM 2022 CD2 HIS ATOM 2023 ND1 HIS ATOM 2024 HD1 HIS ATOM 2025 CEl HIS ATOM 2026 NE2 HIS ATOM 2027 HE2 HIS ATOM 2028 C HIS ATOM 2029 0 HIS ATOM 2030 N TYR 1 0 ATOM 2031 H TYR ATOM 2032 CA TYR ATOM 2033 CB TYR ATOM 2034 CG TYR ATOM 2035 CD1 TYR 15 ATOM 2036 CEl TYR ATOM 2037 CD2 TYR ATOM 2038 CE2 TYR ATOM 2039 CZ TYR ATOM 2040 OH TYR 20 ATOM 2041 HH TYR ATOM 2042 C TYR ATOM 2043 0 TYR ATOM 2044 N LEU ATOM 2045 H LEU 25 ATOM 2046 CA LEU ATOM 2047 CB LEU ATOM 2048 CG LEU ATOM 2049 CD1 LEU ATOM 2050 CD2 LEU ATOM 2051 C LEU ATOM 2052 0 LEU ATOM 2053 N ILE ATOM 2054 H ILE ATOM 2055 CA ILE ATOM 2056 CB ILE ATOM 2057 CG2 ILE ATOM 2058 CG2. ILE ATOM 2059 CD ILE ATOM 2060 C ILE 210 210 210 210 210 210 210 210 211 211 211 211 211 211 211 211 211 211 211 211 211 211 212 212 212 212 212 212 212 212 212 213 213 213 213 213 213 213 28.543 -2.656 -16.468 1.00 24.36 27.881 -3.996 -14.891 1.00 22.98 27.529 -4.364 -14.052 1.00 0.00 28.110 -4.701 -15.967 1.00 22.54 28.506 -3.884 -16.907 1.00 21.56 28.750 -4.161 -17.817 1.00 0.00 26.581 0.172 -13.181 1.00 18.72 27.158 i.225 -13.437 1 .00 17.56 25.888 -0.025 -12.059 1.00 17.28 25.420 -0.876 -11.933 1.00 0.00 25.817 0.927 -10.966 1.00 15.79 24.404 1.190 -10.547 1.00 10.05 23.724 2.032 -11.583 1.00 12.14 23.025 1.419 -12.615 1.00 14.77 22.378 2.205 -13 .576 1.00 17.95 23.793 3.422 -11.497 1.00 13.82 23.146 4.214 -12.450 1.00 14.13 22.440 3.600 -13 .487 1.00 17.28 21.765 4.360 -14.428 1.00 14.60 22.097 5.271 -14.394 1.00 0.00 26.528 0.305 -9.795 1.00 17.49 26.389 -0.900 -9.552 1.00 20.48 27.312 1.111 -9.090 1.00 17.95 27.306 2.074 -9.285 1.00 0.00 28.100 0.653 -7.961 1.00 15.94 29.274 1.590 -7.816 1.00 16.35 30.459 1.166 -7.014 1.00 17.69 30.986 -0.162 -7.495 1.00 21.17 31.528 2.213 -7.189 1.00 23.05 27.230 0.663 -6.724 1.00 15.43 26.326 1.493 -6.647 1.00 17.00 27.397 -0.243 -5.765 1.00 14.45 28.088 -0.934 -5.854 1.00 0.00 26.591 -0.197 -4.566 1.00 12.29 25.504 -1.310 -4.579 1.00 10.74 24.772 -1.292 -3.234 1.00 8.99 24.504 -1.100 -5.725 1.00 9.15 23.386 -2.155 -5.837 1.00 2.00 27.581 -0.409 -3.440 1.00 12.99 281

S

a.

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15 ATOM

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20 ATOM

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25 ATOM

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ATOM

ATOM

2061 0 ILE 2062 N SER 2063 H SER 2064 CA SER 2065 CB SER 2066 OG SER 2067 HG SER 2068 C SER 2069 0 SER 2070 N GLN 2071 H GLN 2072 CA GLN 2073 CB GLN 2074 CG GLN 2075 CD GLN 2076 OE1 GLN 2077 NE2 GLN 2078 HE21 GLN 2079 HE22 GLN 2080 C GLN 2081 0 GLN 2082 N ASP 2083 H ASP 2084 CA ASP 2085 CB ASP 2086 CG ASP 2087 OD1 ASP 2088 0D2 ASP 2089 C ASP 2090 0 ASP 2091 N LYS 2092 H LYS 2093 CA LYS 2094 CB LYS 2095 CG LYS 2096 CD LYS 2097 CE LYS 2098 NZ LYS 2099 HZ1 LYS 213 214 214 214 214 214 214 214 214 215 215 215 215 215 215 215 215 215 215 215 215 216 216 216 216 216 216 216 216 216 217 217 217 217 217 217 217 217 217 26.462 0.921 28.159 -0.172 29.053 -0.568 27.546 -0.162 27.528 -1.599 26.814 -1.698 26.746 -3.095 27 .642 25 .627 24.898 25.607 28.362 29 .604 27.723 26.758 28.456 27.723 26.240 25.830 25.488 28.625 27.872 29.514 30.087 29.754 30.698 30.279 30.563 29.906 30.394 30.186 28.458 -1.266 -3.511 1.00 13.44 27.539 0.409 -2.406 1.00 15.58 26.849 1.103 -2.368 1.00 0.00 28.435 0.266 -1.286 1.00 18.78 29.515 1.352 -1.367 1.00 18.30 30.131 1.374 -2.657 1.00 26.17 29.992 0.512 -3.070 1.00 0.00 27.595 0.401 -0.020 1.00 21.15 -3.924 -3.395 -2.740 -4.263 0.757 0.709 1.654 1.767 2 .492 3 .833 3 .802 2.926 4 .673 1.783 0 .851 2.220 2.958 1.599 2 .467 3 .912 4 .860 6.201 7 .190 6.881 0.001 1.00 18.71 1.035 1.00 23.98 0.974 1.00 0.00 2.338 1.00 28.50 2.792 1.00 22.80 4.085 1.00 25.14 4.636 1.00 29.02 4.521 1.00 34.28 5.265 1.00 30.80 5.289 1.00 0.00 5.713 1.00 0.00 3.262 1.00 33.95 3.248 1.00 36.63 4.016 1.00 34.60 3.899 1.00 0.00 4.953 1.00 40.28 5.154 1.00 43.67 5 .557 1.00 45.13 6 .315 1.00 44.28 5.118 1.00 44.20 6.295 1.00 43.90 6.578 1.00 47.97 7.201 1.00 45.32 6.916 1.00 0.00 8.517 1.00 41.99 9.376 1.00 42.40 9.649 1.00 46.37 8.484 1.00 46.52 8.735 1.00 48.92 7.799 1.00 49.37 6.828 1.00 0.00 282

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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ATOM

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ATOM

ATOM

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ATOM

1 5 ATOM

ATOM

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25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2100 HZ2 LYS 2101 HZ3 LYS 2102 C LYS 2103 0 LYS 2104 N ALA 2105 H ALA 2106 CA ALA 2107 CB ALA 2108 C ALA 2109 0 ALA 2110 N GLY 2111 H GLY 2112 CA GLY 2113 C GLY 2114 0 GLY 2115 N LYS 2116 H LYS 2117 CA LYS 2118 CB LYS 2119 CG LYS 2120 CD LYS 2121 CE LYS 2122 NZ LYS 2123 HZ1 LYS 2124 HZ2 LYS 2125 HZ3 LYS 2126 c LYS 2127 0 LYS 2128 N TYR 2129 H TYR 2130 CA TYR 2131 CB TYR 2132 CG TYR 2133 CD1 TYR 2134 CEl TYR 2135 CD2 TYR 2136 CE2 TYR.

2137 CZ TYR 2138 OH TYR 217 217 217 217 218 218 218 218 218 218 219 219 219 2419 219 220 220 220 220 220 220 220 220 220 220 220 220 220 221 221 221 221 221 221 221 221 221 221 221 31.422 29.924 28.518 28.443 27.521 27.665 26.221 25.535 25.314 24 .112 25.840 26.777 25.102 24 .190 23 .627 24.069 24.534 23 .171 22.620 21.841 21.455 20.193 19.009 18 .175 19 .007 18.983 23.772 24.863 23 .019 22.127 23.425 22.866 23.293 22 .523 22.859 24.411l 24.755 23.969 24.244 7.301 8.099 1.306 0.314 2.178 2.928 2.054 3 .423 0.991 0.914 0.184 0.284 -0.907 -0.554 -1.481 0.703 1.383 1.111l 2.478 2.359 3 .712 4 .202 3 .547 4 .046 3 .607 2.550 1.126 1.647 0.538 0.234 0.359 -0.930 -2.194 -2.686 -3 .901 -2.891 -4 .104 -4 .609 -5.857 7.916 1.00 0.00 7.985 1.00 0.00 9.356 1.00 39.51 10.088 1.00 36.58 9.183 1.00 38.15 8.576 1.00 0.00 9.829 1.00 36.79 9.784 1.00 34.86 9.178 1.00 35.43 9.449 1.00 34.77 8.255 1.00 32.78 8.010 1.00 0.00 7.644 1.00 30.47 6.484 1.00 26.67 5.904 1.00 27.94 6.077 1.00 21.58 6.592 1.00 0.00 5.001 1.00 18.65 5.324 1.00 19.50 6.621 1.00 24.09 7.137 1.00 29.01 6.464 1.00 34.13 6.978 1.00 33.94 6.615 1.00 0.00 8.017 1.00 0.00 6.684 1.00 0.00 3.609 1.00 14.52 3.367 1.00 14.63 2.695 1.00 9.58 2.956 1.00 0.00 1.315 1.00 10.18 0.735 1.00 10.07 1.445 1.00 7.80 2.492 1.00 12.85 3 .088 1.00 17.08 1.000 1.00 9.44 1.596 1.00 18.12 2 .635 1.00 18.06 3.182 1.00 27.12

*C.CC.

283 ATOM 2139 HH TYR 221 ATOM 2140 C TYR 221 ATOM 2141 O TYR 221 ATOM 2142 N CYS 222 ATOM 2143 H CYS 222 ATOM 2144 CA CYS 222 ATOM 2145 CB CYS 222 ATOM 2146 SG CYS 222 ATOM 2147 C CYS 222 ATOM 2148 O CYS 222 ATOM 2149 N ILE 223 ATOM 2150 H ILE 223 ATOM 2151 CA ILE 223 ATOM 2152 CB ILE 223 15 ATOM 2153 CG2 ILE 223 ATOM 2154 CG1 ILE 223 ATOM 2155 CD ILE 223 ATOM 2156 C ILE 223- ATOM 2157 O ILE 223 20 ATOM 2158 N PRO 224 ATOM 2159 CD PRO 224 ATOM 2160 CA PRO 224 ATOM 2161 CB PRO 224 ATOM 2162 CG PRO 224 ATOM 2163 C PRO 224 ATOM 2164 O PRO 224 ATOM 2165 N GLU 225 ATOM 2166 H GLU 225 ATOM 2167 CA GLU 225 ATOM 2168 CB GLU 225 ATOM 2169 CG GLU 225 ATOM 2170 CD GLU 225 ATOM 2171 OE1 GLU 225 ATOM 2172 OE2 GLU 225 ATOM 2173 C GLU 225 ATOM 2174 O GLU 225 ATOM 2175 N GLY 226 ATOM 2176 H GLY 226 ATOM 2177 CA GLY 226 22.930 21.825 23.749 24.666 23.333 23.355 24.969 24.254 25.380 23.725 22.785 24.519 23.572 24.356 22.849 21.823 25.198 24.544 26.451 27.410 27.092 28.376 28.751 26.176 25.757 25.830 26.153 24.988 1.477 0.439 1.00 9.37 2.001 0.636 1.00 8.55 1.842 -0.528 1.00 10.43 1.495 -0.600 1.00 0.00 2.838 -1.489 1.00 13.36 4.241 -0.865 1.00 8.71 4.951 -0.501 1.00 10.62 2.809 -2.697 1.00 13.50 2.292 -2.653 1.00 14.26 3.267 -3.824 1.00 16.58 3.537 -3.825 1.00 0.00 3.485 -5.026 1.00 17.67 3.587 -6.273 1.00 21.79 3.926 -7.550 1.00 19.55 2.257 -6.436 1.00 20.47 2.181 -7.581 1.00 25.28 4.818 -4.710 1.00 15.39 5.635 -4.036 1.00 13.54 5.139 -5.094 1.00 16.61 4.262 -5.761 1.00 11.44 6.417 -4.799 1.00 19.91 6.383 -5.626 1.00 19.31 4.926 -5.508 1.00 17.17 7.590 -5.112 1.00 22.71 7.771 -6.260 1.00 25.97 8.255 -3.999 1.00 22.58 7.878 -3.160 1.00 0.00 9.443 -3.895 1.00 19.95 24.730 -5.725 4.011 1.00 0.00 25.333 10.437 -5.051 1.00 28.14 26.809 10.930 -5.182 1.00 38.98 27.461 10.929 -6.588 1.00 44.42 26.803 11.226 -7.594 1.00 38.07 28.656 10.618 -6.678 1.00 48.45 23.490 9.114 -3.902 1.00 14.73 22.657 10.016 -4.033 1.00 13.50 23.089 7.859 -3.659 1.00 10.41 23.732 7.202 -3.336 1.00 0.00 21.697 7.463 -3.776 1.00 7.22 284

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

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20 ATOM

ATOM

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ATOM

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ATOM

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ATOM

ATOM

ATOM

ATOM

2178 C GLY 2179 o GLY 2180 N THR 2181 H THR 2182 CA THR 2183 CB THR 2184 OGi THR 2185 HG1 THR 2186 CG2 THR 2187 c THR 2188 0 THR 2189 N LYS 2190 H LYS 2191 CA LYS 2192 CB LYS 2193 CG LYS 2194 CD LYS 2195 CE LYS 2196 NZ LYS 2197 HZ1 LYS 2198 HZ2 LYS 2199 HZ3 LYS 2200 C LYS 2201 0 LYS 2202 N PHE 2203 H PHE 2204 CA PHE 2205 CB PHE 2206 CG PHE 2207 CD1 PHE 2208 CD2 PHE 2209 CEl PHE 2210 CE2 PHE 2211 CZ PHE 2212 c PHE 2213 o PHE 2214 N ASP 2215 H ASP 2216 CA ASP 226 226 227 227 227 227 227 227 227 227 227 228 228 228 228 228 228 228 228 228 228 228 228 228 229 229 229 229 229 229 229 229 229 229 229 229 230 230 230 20.986 21.524 19.735 19.304 18.909 17. 544 17.248 16.969 16.382 19.563 20.207 19.465 18.953 20.027 20.479 21.337 22.464 23.498 24.485 25.167 24.987 24.014 18.945 17.772 19.335 20.283 18.434 18.161 17 .602 18.451 16.255 17.948 15.758 16.599 19.133 20.356 6.211 7.345 8.067 6.076 5.440 4.542 5.533 6 .274 4.523 5.067 6.290 6.201 7.216 6 .542 7.233 5.841 6.058 3.509 3 .879 2.239 2.022 1.143 0.236 1.035 1.524 1.330 2.314 2. 122 2 .612 0.306 0.321 -1.937 1.00 3.12 -2.725 1.00 12.83 -2.140 1.00 0.00 -0.988 1.00 2.69 -0.562 1.00 8.27 -1.117 1.00 8.17 0.758 1.00 9.07 1.161 1.00 0.00 1.630 1.00 10.14 2.971 1.00 15.14 3.029 1.00 19.45 2.058 1.00 21.10 2.476 1.00 29.17 3.294 1.00 35.96 3.663 1.00 0.00 2.712 1.00 0.00 4.086 1.00 0.00 1.947 1.00 8.99 2.070 1.00 2.97 2.074 1.00 7.55 1.957 1.00 0.00 2.403 1.00 7.13 1.202 1.00 7.36 0.047 1.00 2.00 -0.944 1.00 8.70 0.001 1.00 4.73 -1.976 1.00 4.18 -1.033 1.00 4.26 -2.016 1.00 2.00 3.455 1.00 9.26 3.597 1.00 8.05 4.215 1.00 9.93 4.097 1.00 0.00 5.183 1.00 11.63 7.289 -2.455 1.00 8.63 7.576 -1.378 1.00 14.32 6.849 -2.535 1.00 10.35 6.740 -3.409 1.00 0.00 6.566 -1.373 1.00 7.32 18.393 -0.461 17.419 -0.468 19.041 -1.318 285

S.

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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ATOM

20 ATOM

ATOM

ATOM

ATOM

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ATOM

ATOM

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ATOM

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ATOM

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ATOM

2217 CB ASP 2218 CG ASP 2219 OD1 ASP 2220 OD2 ASP 2221 C ASP 2222 O ASP 2223 N THR 2224 H THR 2225 CA THR 2226 CB THR 2227 OG1 THR 2228 HG1 THR 2229 CG2 THR 2230 C THR 2231 O THR 2232 N LEU 2233 H LEU 2234 CA LEU 2235 CB LEU 2236 CG LEU 2237 CD1 LEU 2238 CD2 LEU 2239 C LEU 2240 0 LEU 2241 N TRP 2242 H TRP 2243 CA TRP 2244 CB TRP 2245 CG TRP 2246 CD2 TRP 2247 CE2 TRP 2248 CE3 TRP 2249 CD1 TRP 2250 NE1 TRP 2251 HE1 TRP 2252 CZ2 TRP 2253 CZ3 TRP 2254 CH2 TRP 2255 C TRP 230 230 230 230 230 230 231 231 231 231 231 231 231 231 231 232 232 232 232 232 232 232 232 232 233 233 233 233 233 233 233 233 233 233 233 233 233 233 233 18.125 -1.490 18.175 -0.350 19.033 0.524 17.358 -0.353 19.424 -2.679 20.264 -3.360 18.797 -3.145 18.165 -2.584 19.108 -4.445 17.962 -5.429 16.791 -4.882 16.387 -4.307 17.723 -5.654 19.293 -4.277 18.720 -3.348 20.040 -5.146 20.535 -5.828 20.134 -5.089 21.146 -6.078 22.538 -5.695 22.670 -4.204 23.519 -6.259 18.788 -5.422 18.446 -4.879 17.959 -6.266 18.236 -6.662 16.650 -6.611 15.903 -7.634 14.559 -8.122 13.319 -7.504 12.516 -8.393 12.743 -6.346 14.503 -9.298 13.249 -9.419 12.886 -10.159 11.156 -8.154 11.386 -6.098 10.597 -7.001 15.776 -5.389 6.382 1.00 7.41 7.397 1.00 10.95 7.281 1.00 10.94 8.326 1.00 12.05 4.643 1.00 12.18 5.220 1.00 15.45 3.565 1.00 14.62 3.072 1.00 0.00 3.000 1.00 11.96 3.266 1.00 6.38 2.696 1.00 8.91 3.370 1.00 0.00 4.750 1.00 8.69 1.508 1.00 9.43 0.929 1.00 10.77 0.840 1.00 6.23 1.341 1.00 0.00 -0.598 1.00 2.95 -1.084 1.00 2.00 -1.570 1.00 7.83 -1.804 1.00 6.14 -0.588 1.00 5.92 -1.210 1.00 3.62 -2.256 1.00 11.85 -0.590 1.00 7.60 0.263 1.00 0.00 -1.119 1.00 3.89 -0.232 1.00 5.05 -0.793 1.00 3.68 -0.707 1.00 7.30 -1.406 1.00 2.00 -0.161 1.00 5.75 -1.485 1.00 2.00 -1.834 1.00 2.00 -2.387 1.00 0.00 -1.566 1.00 5.63 -0.314 1.00 2.00 -1.012 1.00 11.94 -1.218 1.00 8.61 286 es..

ATOM

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ATOM

ATOM

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1 5 ATOM

ATOM

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20 ATOM

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2256 0 TRP 2257 N GLN 2258 H GLN 2259 CA GLN 2260 CB GLN 2261 CG GLN 2262 CD GLN 2263 OE1 GLN 2264 NE2 GLN 2265 HE21 GLN 2266 HE22 GLN 2267 C GLN 2268 0 GLN 2269 N LEU 2270 H LEU 2271 CA LEU 2272 CB LEU 2273 CG LEU 2274 CD1 LEU 2275 CD2 LEU 2276 C LEU 2277 0 LEU 2278 N VAL 2279 H VAL 2280 CA VAL 2281 CB VAL 2282 CG1 VAL 2283 CG2 VAL 2284 c VAL 2285 o VAL 2286 N GLU 2287 H GLU 2288 CA GLU 2289 CB GLU 2290 CG GLU 2291 CD GLtJ 2292 OE1 GLU 2293 0E2 GLU 2294 C GLU 233 234 234 234 234 234 234 234 234 234 234 234 234 235 235 235 235 235 235 235 235 235 236 236 236 236 236 236 236 236 237 237 237 237 237 237 237 237 237 15.050 -5.243 -2.208 1.00 5.31 15.757 -4.569 -0.160 1.00 7.54 16.278 -4.789 0.645 1.00 0.00 14.936 -3.379 -0.181 1.00 5.71 14.898 -2.731 1.182 1.00 8.39 13.956 -3.432 2.121 1.00 10.31 14.065 -2.931 3.557 1.00 11.00 15.131 -3.022 4.161 1.00 6.43 13.010 -2.409 4.171 1.00 6.16 12.163 -2.384 3.672 1.00 0.00 13.119 -2.107 5.091 1.00 0.00 15.479 -2.388 -1.194 1.00 3.99 14.693 -1.634 -1.757 1.00 8.14 16.775 -2.345 -1.489 1.00 5.43 17.407 -2.893 -0.976 1.00 0.00 17.285 -1.460 -2.527 1.00 8.35 18.831 -1.563 -2.577 1.00 2.00 19.649 -0.729 -3.596 1.00 2.00 20.947 -0.300 -2.980 1.00 2.00 20.012 -1.545 -4.817 1.00 4.96 16.659 -1.826 -3.873 1.00 12.15 16.060 -0.967 -4.545 1.00 13.16 16.710 -3.120 -4.220 1.00 9.84 17.132 -3.757 -3 .603 1.00 0.00 16.185 -3 .580 -5.494 1.00 9.17 16.477 -5.079 -5 .682 1.00 8.00 15.742 -5.655 -6.880 1.00 9.58 17.968 -5.216 -5.949 1.00 3.72 14.707 -3.320 -5.616 1.00 9.31 14.278 -2.681 -6.586 1.00 17.05 13.942 -3.715 -4.602 1.00 7.98 14.359 -4.221 -3 .874 1.00 0.00 12.507 -3.526 -4.598 1.00 5.37 11.923 -4.003 -3.284 1.00 4.42 10.399 -4.242 -3.284 1.00 9.65 9.844 -5.417 -4.113 1.00 13.56 8.630 -5.457 -4.307 1.00 22.81 10.589 -6.290 -4.562 1.00 14.84 12.079 -2.091 -4.814 1.00 8.52 287 0

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

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20 ATOM

ATOM

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ATOM

ATOM

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2295 o GLU 2296 N TYR 2297 H TYR 2298 CA TYR 2299 CB TYR 2300 CG TYR 2301. CD1 TYR 2302 CEl TYR 2303 CD2 TYR 2304 CE2 TYR 2305 CZ TYR 2306 OH TYR 2307 HH TYR 2308 c TYR 2309 0 TYR 2310 N LEU 2311 H LEU 2312 CA LEU 2313 CB LEU 2314 CG LEU 2315 CD1 LEU 2316 CD2 LEU 2317 C LEU 2318 0 LEU 2319 N LYS 2320 H LYS 2321 CA LYS 2322 CB LYS 2323 CG LYS 2324 CD LYS 2325 CE LYS 2326 NZ LYS 2327 HZ1 LYS 2328 HZ2 LYS 2329 HZ3 LYS 2330 C LYS 2331 0 LYS 2332 N LEU 2333 H LEU 237 238 238 238 238 238 238 238 238 238 238 238 238 238 238 239 239 239 239 239 239 239 239 239 240 240 240 240 240 240 240 240 240 240 240 240 240 241 241 11.084 12.844 13.719 12 .449 13.315 12.969 12 .065 11. 766 13 .576 13.277 12.380 12 .118 11.600 12 .658 11.825 13 .764 14.358 14.169 15.631 16. 612 18 .003 16.458 13.357 13.533 12 .525 12.628 11.598 11.086 12 .080 11.241 12 .104 11.320 10 .510 10 .971 11 .912 10.393 9 .710 10 .121 10 .722 -1.831 -5.485 1.00 11.94 -1.118 -4.334 1.00 9.87 -1.342 -3.953 1.00 0.00 0.269 -4.405 1.00 8.12 1.018 -3.400 1.00 12.67 2.471 -3.148 1.00 12.96 2.796 -2.126 1.00 6.34 4.'41 -1.884 1.00 8.90 3.482 -3.925 1.00 12.47 4.823 -3.672 1.00 7.42 5.142 -2.656 1.00 8.04 6.469 -2.398 1.00 10.73 6.534 -1.589 1.00 0.00 0.760 -5.827 1.00 10.55 1.506 -6.348 1.00 9.33 0.323 -6.443 1.00 12.05 -0.294 -5.962 1.00 0.00 0.725 -7.784 1.00 10.14 0.379 -8.015 1.00 11.39 1.015 -7.051 1.00 9.45 0.616 -7.428 1.00 4.78 2.515 -7.075 1.00 11.26 0.078 -8.873 1.00 9.57 0.339 -10.054 1.00 9.15 -0.867 -8.476 1.00 15.55 -1.226 -7.572 1.00 0.00 -1.526 -9.359 1.00 17.48 -2.846 -8.804 1.00 17.46 -3.968 -8.744 1.00 15.22 -5.061 -8.143 1.00 14.34 -6.285 -7.941 1.00 18.77 -7.303 -7.288 1.00 14.93 -7.562 -7.887 1.00 0.00 -6.935 -6.381 1.00 0.00 -8.142 -7.119 1.00 0.00 -0.647 -9.532 1.00 21.00 -0.714 -10.561 1.00 24.63 0.155 -8.496 1.00 22.22 0.171 -7.725 1.00 0.00 288 ATOM 2334 CA LEU 241 r r r

ATOM

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ATOM

ATOM

ATOM

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ATOM

ATOM

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15 ATOM

ATOM

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2335 CB LEU 2336 CG LEU 2337 CD1 LEU 2338 CD2 LEU 2339 C LEU 2340 O LEU 2341 N LYS 2342 H LYS 2343 CA LYS 2344 CB LYS 2345 CG LYS 2346 CD LYS 2347 CE LYS 2348 NZ LYS 2349 HZ1 LYS 2350 HZ2 LYS 2351 HZ3 LYS 2352 C LYS 2353 O LYS 2354 N ALA 2355 H ALA 2356 CA ALA 2357 CB ALA 2358 C ALA 2359 O ALA 2360 N ASP 2361 H ASP 2362 CA ASP 2363 CB ASP 2364 CG ASP 2365 OD1 ASP 2366 OD2 ASP 2367 C ASP 2368 O ASP 2369 N GLY 2370 H GLY 2371 CA GLY 2372 C GLY 241 241 241 241 241 241 242 242 242 242 242 242 242 242 242 242 242 242 242 243 243 243 243 243 243 244 244 244 244 244 244 244 244 244 245 245 245 245 9.240 8.443 10.365 11.030 10.736 10.562 9.096 8.908 9.326 8.973 7.964 9.549 9.156 12.192 13.044 12.492 11.770 13.841 13.949 14.883 16.030 14.528 13.631 15.399 15.314 15.807 15.432 16.551 16.834 17.841 16.948 16.134 18.239 18.811 2.402 -8.922 1.00 20.05 2.970 -9.660 1.00 27.60 2.968 -8.472 1.00 18.36 2.419 -8.002 1.00 0.00 4.355 -8.708 1.00 18.26 5.193 -7.429 1.00 19.41 5.447 -7.114 1.00 17.62 6.480 -6.033 1.00 14.02 5.989 -4.671 1.00 10.78 6.952 -3.638 1.00 12.29 7.198 -3.716 1.00 0.00 7.808 -3.757 1.00 0.00 6.528 -2.709 1.00 0.00 4.371 -9.123 1.00 18.38 3.948 -8.340 1.00 23.83 4.869 -10.327 1.00 18.80 5.267 -10.850 1.00 0.00 4.812 -10.887 1.00 19.06 5.553 -12.237 1.00 15.73 5.412 -9.975 1.00 16.76 4.971 -10.012 1.00 16.14 6.456 -9.214 1.00 13.41 6.846 -9.318 1.00 0.00 7.026 -8.202 1.00 14.59 6.027 -7.034 1.00 18.56 6.513 -5.697 1.00 15.45 7.607 -5.302 1.00 14.61 5.779 -5.058 1.00 15.49 7.347 -8.637 1.00 14.32 7.119 -7.947 1.00 17.05 7.902 -9.840 1.00 17.98 8.056 -10.361 1.00 0.00 8.279 -10.368 1.00 10.81 7.304 -11.369 1.00 11.69 8.936 0.992 -8.503 1.00 21.50 8.312 0.984 -7.111 1.00 22.84 8.099 -0.392 -6.506 1.00 25.03 7.695 -0.270 -5.047 1.00 28.03 7.086 -1.136 -7.365 1.00 27.90 289 ATOM 2373 0 GLY 245 ATO 233 0 GLY 245 19.760 7.670 -12.059 1.00 14.24 p

ATOM

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ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM*

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2374 N LEU 2375 H LEU 2376 CA LEt? 2377 CB LEt? 2378 CG LEt? 2379 CD1 LEt? 230 D LEt? 2381 C LEt? 2382 0 LEt? 2383 N ILE 2384 H ILE 2385 CA ILE 2386 CB ILE 2387 CG2 ILE 2388 CG1 ILE 2389 CD ILE 2390 C ILE 2391 0 ILE 2392 N TYR 2393 H TYR 2394 CA TYR 2395 CB TYR 2396 CG TYR 2397 CD1 TYR 2398 CEl TYR 2399 CD2 TYR 2400 CE2 TYR 2401 CZ TYR 2402 OH TYR 2403 HH TYR 2404 C TYR 2405 o TYR 2406 N CYS 2407 H CYS 2408 CA CYS 2409 CB CYS 2410 SG CYS 2411 c CYS 246 246 246 246 246 246 246 246 246 247 247 247 247 247 247 247 247 247 248 248 248 248 248 248 248 248 248 248 248 248 248 248 249 249 249 249 249 249 18.279 17.538 18.736 18.123 18. 387 17.581 19.866 18.322 17.378 19.004 19.848 18.640 19.743 19.762 19.461 19.246 17.267 16.548 16.839 17.362 15.562 15 .690 14.358 13.932 12 .710 13 .564 12.343 11.926 10.723 10.182 15.197 16.116 13 .897 13.238 13 .422 11.901 11.404 13.753 6.091 -11.484 1.00 15.09 5.845 -10.890 1.00 0.00 5.089 -12.451 1.00 16.67 3.729 -12.247 1.00 12.64 2.880 -11.055 1.00 12.13 1.601 -11.239 1.00 16.26 2.604 -0.8906 .00L 7.94 5.465 -13.861 1.00 17.17 6.237 -14.033 1.00 16.84 4.899 -14.859 1.00 18.24 4.448 -14.647 1.00 0.00 5.084 -16.243 1.00 19.23 4.443 -17.166 1.00 21.02 2.933 -17.037 1.00 18.75 4.744 -18.623 1.00 18.10 6.228 -18.940 1.00 26.97 4.479 -16.501 1.00 24.15 4.963 -17.381 1.00 27.80 3.453 -15.764 1.00 22.21 3.113 -15.008 1.00 0.00 2.810 -16.014 1.00 21.62 1.863 -17.222 1.00 21.58 1.459 -17.836 1.00 22.46 0.136 -17.768 1.00 25.31 -0.232 -18.321 1.00 25.82 2.420 -18.464 1.00 24.69 2.057 -19.030 1.00 20.76 0.733 -18.952 1.00 22.54 0.368 -19.518 1.00 26.05 1.145 -19.684 1.00 0.00 2.013 -14.771 1.00 20.39 1.543 -14.091 1.00 21.20 1.885 -14.469 1.00 16.84 2.385 -14.998 1.00 0.00 1.032 -13.382 1.00 15.26 1.106 -13.174 1.00 14.09 2.626 -12.300 1.00 18.14 -0.412 -13.666 1.00 14.21 290 ATOM 2412 ATOM 2413 ATOM 2414 ATOM 2415 ATOM 2416 ATOM 2417 ATOM 2418 ATOM 2419 ATOM 2420 ATOM 2421 ATOM 2422 ATOM 2423 ATOM 2424 ATOM 2425 1 5 ATOM 2426 ATOM 2427 ATOM 2428 ATOM 2429 ATOM 2430 ATOM 2431 ATOM 2432 ATOM 2433 ATOM 2434 ATOM 2435 ATOM 2436 ATOM 2437 ATOM 2438 ATOM 2439 ATOM 2440 ATOM 2441 ATOM 2442 ATOM 2443 ATOM 2444 ATOM 2445 ATOM 2446 ATOM 2447 ATOM 2448 ATOM 2449 ATOM 2450

O

N

H

CA

CB

CG

CD1 CD2

C

0

N

H

CA

CB

CG

CD

CE

NZ

HZ1 HZ2 HZ3

C

O

N

H

CA

CB

CG

CD

OE1 OE2

CYS

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

GLU

ALA

ALA

ALA

249 250 250 250 250 250 250 250 250 250 251 251 251 251 251 251 251 251 251 251 251 251 251 252 252 252 252 252 252 252 252 252 252 253 253 253 253 253 253 13.773 14.025 13.948 14.352 14.919 16.117 16.561 17.241 13.064 11.987 13.147 14.026 11.974 11.594 10.932 10.358 9.335 8.508 8.015 9.095 7.805 12.281 12.298 12.577 12.735 12.808 12.753 12.915 13.832 13.632 14.760 14.140 15.182 14.133 13.277 15.354 15.051 16.032 15.406 -0.843 -1.151 -0.736 -2.561 -3.094 -2.358 -3.102 -2.245 -3.292 -2.905 -4.314 -4.664 -5.035 -4.599 -3.252 -3.321 -2.219 -2.570 -3.461 -2.696 -1.824 -6.529 -7.107 -7.221 -6.759 -8.649 -9.113 -10.598 -10.890 -10.336 -11.678 -9.005 -8.416 -9.980 -10.377 -10.499 -11.274 -11.469 -12.393 -14.823 -12.589 -11.703 -12.686 -11.360 -10.789 -9.557 -11.807 -13.029 -12.563 -13.870 -14.120 -14.309 -15.727 -15.911 -17.316 -17.552 -18.689 -18.478 -19.538 -18.854 -14.273 -13.187 -15.372 -16.224 -15.349 -16.799 -17.097 -18.277 -19.360 -18.098 -14.690 -14.990 -13.786 -13.540 -13.186 -11.919 -14.153 -14.672 1.00 14.52 1.00 13.28 1.00 0.00 1.00 15.78 1.00 6.33 1.00 6.54 1.00 5.37 1.00 8.52 1.00 18.36 1.00 20.40 1.00 21.41 1.00 0.00 1.00 29.19 1.00 31.81 1.00 36.36 1.00 46.04 1.00 49.77 1.00 47.05 1.00 0.00 1.00 0.00 1.00 0.00 1.00 31.19 1.00 32.83 1.00 29.48 1.00 0.00 1.00 27.78 1.00 33.80 1.00 42.74 1.00 44.39 1.00 48.44 1.00 45.82 1.00 24.46 1.00 23.91 1.00 22.26 1.00 0.00 1.00 23.18 1.00 20.69 1.00 25.29 1.00 25.19 CB ALA C ALA O ALA 291 ATOM 2451 N CYS 254 17.302 -11.290 -14.458 1.00 28.10 ATOM 2452 H CYS 254 17.789 -10.541 -14.055 1.00 0.00 ATOM 2453 CA CYS 254 18.009 -12.221 -15.306 1.00 32.61 ATOM 2454 CB CYS 254 19.237 -11.516 -15.870 1.00 31.75 ATOM 2455 SG CYS 254 20.443 -12.611 -16.651 1.00 32.44 ATOM 2456 C CYS 254 18.385 -13.402 -14.414 1.00 36.58 ATOM 2457 0 CYS 254 19.302 -13.243 -13.604 1.00 32.66 ATOM 2458 N PRO 255 17.736 -14.582 -14.469 1.00 42.06 ATOM 2459 CD PRO 255 16.816 -15.010 -15.511 1.00 44.90 1 0 ATOM 2460 CA PRO 255 17.881 -15.667 -13.508 1.00 46.64 ATOM 2461 CB PRO 255 16.693 -16.572 -13.752 1.00 45.44 ATOM 2462 CG PRO 255 15.803 -15.772 -14.666 1.00 45.18 ATOM 2463 C PRO 255 19.209 -16.379 -13.699 1.00 52.71 ATOM 2464 o PRO 255 19.967 -16.514 -12.736 1.00 51.83 oooo 1 5 ATOM 2465 N ASN 256 19.423 -16.849 -14.938 1.00 57.99 g ATOM 2466 H ASN 256 18.668 -16.918 -15.559 1.00 0.00 ATOM 2467 CA ASN 256 20.623 -17.469 -15.488 1.00 62.54 ATOM 2468 CB ASN 256 21.441 -18.299 -14.490 1.00 65.25 ATOM 2469 CG ASN 256 22.929 -18.083 -14.712 1.00 66.81 20 ATOM 2470 ODI ASN 256 23.634 -17.431 -13.921 1.00 67.18 coo.

ATOM 2471 ND2 ASN 256 23.440 -18.585 -15.825 1.00 67.62 ATOM 2472 HD21 ASN 256 22.782 -18.992 -16.444 1.00 0.00 ATOM 2473 HD22 ASN 256 24.395 -18.528 -15.990 1.00 0.00 ATOM 2474 C ASN 256 20.177 -18.438 -16.589 1.00 64.50 ATOM 2475 o ASN 256 20.971 -18.719 -17.481 1.00 67.70 ATOM 2476 OT ASN 256 19.021 -18.861 -16.603 1.00 65.26 ATOM 2477 CB ASN 301 36.860 -2.320 -19.345 1.00 69.57 ATOM 2478 CG ASN 301 36.797 -2.379 -20.870 1.00 73.37 ATOM 2479 ODI ASN 301 35.914 -1.729 -21.445 1.00 74.19 ATOM 2480 ND2 ASN 301 37.648 -3.095 -21.595 1.00 71.92 ATOM 2481 HD21 ASN 301 38.347 -3.615 -21.146 1.00 0.00 ATOM 2482 HD22 ASN 301 37.539 -3.068 -22.570 1.00 0.00 ATOM 2483 C ASN 301 35.546 -1.915 -17.229 1.00 62.96 ATOM 2484 0 ASN 301 35.538 -2.834 -16.427 1.00 64.29 ATOM 2485 HT1 ASN 301 35.437 -0.113 -19.057 1.00 0.00 ATOM 2486 HT2 ASN 301 33.944 -0.750 -18.698 1.00 0.00 ATOM 2487 N ASN 301 34.823 -0.927 -19.230 1.00 62.99 ATOM 2488 HT3 ASN 301 34.663 -1.030 -20.256 1.00 0.00 ATOM 2489 CA ASN 301 35.463 -2.137 -18.724 1.00 65.07 292 ATOM 2490 ATOM 2491 ATOM 2492 ATOM 2493 ATOM 2494 ATOM 2495 ATOM 2496 ATOM 2497 ATOM 2498 1 0 ATOM 2499 ATOM 2500 ATOM 2501 ATOM 2502 ATOM 2503 1 5 ATOM 2504 ATOM 2505 ATOM 2506 ATOM 2507 ATOM 2508 20 ATOM 2509 ATOM 2510 ATOM 2511 ATOM 2512 ATOM 2513 ATOM 2514 ATOM 2515 ATOM 2516 ATOM 2517 ATOM 2518 ATOM 2519 ATOM 2520 ATOM 2521 ATOM 2522 ATOM 2523 ATOM 2524 ATOM 2525 ATOM 2526 ATOM 2527 ATOM 2528 N GLN H GLN CA. GLN CB GLN CG GLN CD GLN OE1 GLN NE2 GLN HE21 GLN HE22 GLN C GLN O GLN N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N PTY H PTY CA PTY CB PTY CG PTY CD1 PTY CE1 PTY CD2 PTY CE2 PTY CZ PTY OH PTY OR1 PTY OR2 PTY OR3 PTY PR PTY C PTY O PTY N ASN 302 302 302 302 302 302 302 302 302 302 302 302 303 303 303 303 303 303 303 303 303 304 304 304 304 304 304 304 304 304 304 304 304 304 304 304 304 304 305 35.788 36.395 35.444 36.677 37.907 38.599 -1.034 38.352 -0.683 39.485 -2.004 39.677 -2.304 39.918 -2.371 34.360 0.845 33.831 0.670 34.058 1.917 34.536 2.006 33.028 2.927 32.932 3.417 33.369 4.825 34.886 4.916 32.860 5.183 31.624 2.471 30.919 1.703 31.253 2.987 31.821 3.642 29.936 2.775 30.043 2.545 30.722 1.239 29.995 0.026 30.618 -1.204 32.114 1.170 32.746 -0.058 32.004 -1.261 32.693 -2.423 32.971 -4.897 34.118 -3.534 31.717 -3.857 32.822 -3.701 29.189 4.049 29.765 5.121 27.890 3.929 -0.672 -0.113 -0.176 0.491 -0.432 -16.851 -17.375 -15.522 -14.883 -14.691 -15.937 -17.103 -15.770 -14.860 -16.565 -15.961 -17.088 -15.204 -14.354 -15.484 -16.940 -17.292 -17.295 -18.676 -15.160 -15.820 -14.015 -13.563 -13.481 -11.983 -11.678 -11.631 -11.387 -11.468 -11.223 -11.185 -10.923 -11.058 -12.638 -12.879 -11.913 -13.805 -14.023 -13.870 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 60.20 0.00 56.74 57.90 63.47 65.28 66.79 65.62 0.00 0.00 52.62 54.45 44.49 0.00 34.84 31.82 30.98 31.39 32.60 31.46 30.32 29.09 0.00 25.08 22.52 20.76 19.61 18.55 23.88 28.36 23.76 28.36 28.97 33.20 30.35 29.14 24.98 32.82 23.83 293 ATOM 2529 H ASN 305 27.489 3.081 -13.594 1.00 0.00 ATOM 2530 CA ASN 305 27.030 5.042 -14.190 1.00 24.41 ATOM 2531 CB ASN 305 25.758 4.572 -14.824 1.00 26.42 ATOM 2532 CG ASN 305 25.898 3.944 -16.184 1.00 24.24 ATOM 2533 ODI ASN 305 25.035 4.171 -17.007 1.00 33.32 ATOM 2534 ND2 ASN 305 26.883 3.141 -16.534 1.00 27.31 ATOM 2535 HD21 ASN 305 27.568 2.878 -15.888 1.00 0.00 ATOM 2536 HD22 ASN 305 26.910 2.846 -17.468 1.00 0.00 ATOM 2537 C ASN 305 26.646 5.788 -12.931 1.00 26.89 ATOM 2538 0 ASN 305 26.463 5.181 -11.870 1.00 26.21 ATOM 2539 N GLU 306 26.502 7.098 -13.029 1.00 26.87 ATOM 2540 H GLU 306 26.619 7.529 -13.901 1.00 0.00 ATOM 2541 CA GLU 306 26.052 7.888 -11.905 1.00 29.02 ATOM 2542 CB GLU 306 26.708 9.275 -11.886 1.00 32.98 oo*o 1 5 ATOM 2543 CG GLU 306 26.552 10.101 -13.156 1.00 35.35 ATOM 2544 CD GLU 306 26.731 11.581 -12.905 1.00 36.20 ATOM 2545 OE1 GLU 306 25.760 12.318 -13.089 1.00 39.79 ATOM 2546 OE2 GLU 306 27.833 11.985 -12.528 1.00 39.08 ATOM 2547 C GLU 306 24.554 8.067 -12.017 1.00 26.18 20 ATOM 2548 0 GLU 306 23.999 7.923 -13.109 1.00 26.43 oooo ATOM 2549 N LEU 307 23.926 8.432 -10.904 1.00 26.19 ATOM 2550 H LEU 307 24.434 8.578 -10.080 1.00 0.00 ATOM 2551 CA LEU 307 22.512 8.679 -10.915 1.00 26.40 ATOM 2552 CB LEU 307 21.819 8.244 -9.639 1.00 28.26 ATOM 2553 CG LEU 307 22.362 8.248 -8.253 1.00 30.34 ATOM 2554 CD1 LEU 307 21.230 8.042 -7.267 1.00 31.01 ATOM 2555 CD2 LEU 307 23.357 7.136 -8.115 1.00 28.88 ATOM 2556 C LEU 307 22.119 10.118 -11.130 1.00 25.17 ATOM 2557 o LEU 307 22.824 11.077 -10.810 1.00 25.91 ATOM 2558 N ASN 308 20.929 10.231 -11.692 1.00 23.16 ATOM 2559 H ASN 308 20.474 9.395 -11.916 1.00 0.00 ATOM 2560 CA ASN 308 20.285 11.497 -11.977 1.00 22.52 ATOM 2561 CB ASN 308 19.149 11.318 -12.993 1.00 22.41 ATOM 2562 CG ASN 308 19.569 10.764 -14.349 1.00 17.49 ATOM 2563 ODI ASN 308 20.482 11.269 -15.006 1.00 18.25 ATOM 2564 ND2 ASN 308 18.899 9.712 -14.812 1.00 12.44 ATOM 2565 HD21 ASN 308 18.211 9.290 -14.262 1.00 0.00 ATOM 2566 HD22 ASN 308 19.116 9.403 -15.722 1.00 0.00 ATOM 2567 C ASN 308 19.714 11.910 -10.638 1.00 23.34 294 ATOM 2568 0 ASN 308 18.580 11.582 -10.279 1.00 19.95 15 4

A

A

A

A

A

A

A

A

A

A

A

A

p

A

A

A

ATOM 2569 ATOM 2570 ATOM 2571 ATOM 2572 ATOM 2573 ATOM 2574 ATOM 2575 ATOM 2576 ATOM 2577 ATOM 2578 ATOM 2579 ATOM 2580 ATOM 2581 ATOM 2582 ATOM 2583 ATOM 2584 ATOM 2585 ATOM 2586 ATOM 2587 ATOM 2588 ATOM 2589 ATOM 2590 ATOM 2591 ATOM 2592 ATOM 2593 ATOM 2594 ATOM 2595 ATOM 2596 kTOM 2597 TOM 2598 kTOM 2599 %TOM 2600 TOM 2601 TOM 2602 TOM 2603 TOM 2604 TOM 2605 TOM 2606

N

H

CA

CB

CG

CD1

C

0

N

H

CA

C

0

N

H

CA

CB

CG

CD

NE

HE

Cz NH1 HH11 HH12 NH2 HH21 HH22

C

0

N

H

CA

CB

CG

CD

NE

LEU

LEU

LEU

LEU

LEU

LEU

T ET?

LEU

LEU

GLY

GLY

GLY

GLY

GLY

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

309 309 309 309 309 309 309 309 309 310 310 310 310 310 311 311 311 311 311 311 311 311 311 311 311 311 311 311 311 311 311 312 312 312 312 312 312 312 20.511 21.402 20.143 21.281 22.549 23.498 22.233 18.857 18.184 18.453 18.976 17.179 15.983 14.841 16.223 17.136 15.167 15.520 15.337 13.858 13.085 13.270 12.120 11.757 12.203 11.030 11.490 11.739 10.779 14.970 14.321 15.562 16.027 15.398 16.685 17.790 19.017 18.651 12.640 -9.874 12.862 -10.222 13.022 -8.516 13.803 -7.886 13.034 -7.551 13.976 -6.828 11.839 -6.f'70 13.811 -8.352 13.676 -7.327 14.571 -9.376 14.564 -10.197 15.284 -9.330 14.351 -9.552 14.792 -9.660 13.050 -9.692 12.716 -9.635 12.087 -9.890 11.222 -11.115 11.959 -12.441 12.286 -12.617 11.087 -12.889 10.598 -13.718 10.608 -12.098 11.199 -10.944 12.040 -10.636 10.791 -10.389 9.497 -12.482 9.048 -13.337 9.100 -11.899 11.229 -8.650 10.178 -8.704 11.638 -7.528 12.501 -7.525 10.960 -6.245 10.983 -5.444 10.119 -6.047 10.171 -5.167 10.046 -3.764 1.00 29.40 1.00 0.00 1.00 31.98 1.00 31.78 1.00 30.04 1.00 32.49 1LV nA nn I 1.00 32.71 1.00 33.18 1.00 29.51 1.00 0.00 1.00 27.02 1.00 26.12 1.00 24.61 1.00 26.37 1.00 0.00 1.00 26.85 1.00 28.37 1.00 22.17 1.00 20.22 1.00 22.46 1.00 0.00 1.00 30.68 1.00 37.34 1.00 0.00 1.00 0.00 1.00 24.13 1.00 0.00 1.00 0.00 1.00 26.76 1.00 27.21 1.00 24.91 1.00 0.00 1.00 19.46 1.00 18.55 1.00 18.34 1.00 16.42 1.00 12.29 295

S

S

S S

S.

S

5*

S

S

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S

ATOM 2607 HE ARG ATOM 2608 CZ ARC ATOM 2609 NH1 ARC ATOM 2610 HH11 ARC ATOM 2611 HH12 ARC ATOM 2612 NH2 ARG ATOM 2613 HH21 ARG r 1- 2634 HH2A ATOM 2615 c ARG ATOM 2616 0 ARG ATOM 2617 N GLU ATOM 2618 H GLU ATOM 2619 CA GLU ATOM 2620 CB GLU 15 ATOM 2621 CC GLU ATOM 2622 CD GLU ATOM 2623 OE1 CLU ATOM 2624 0E2 GLU ATOM 2625 c GLU ATOM 2626 0 GLU ATOM 2627 N GLU ATOM 2628 H GLU ATOM 2629 CA GLU ATOM 2630 CB GLU ATOM 2631 CC GLU ATOM 2632 CD CLU ATOM 2633 OE1 GLU ATOM 2634 0E2 GLU ATOM 2635 c GLU ATOM 2636 o GLU ATOM 2637 N PTY ATOM 2638 H PTY ATOM 2639 CA PTY ATOM 2640 CE PTY ATOM 2641 CG PTY ATOM 2642 CD1 PTY ATOM 2643 CEl PTY ATOM 2644 CD2 PTY ATOM 2645 CE2 PTY 312 312 312 312 312 312 312 312 312 313 313 313 313 313 313 313 313 313 313 314 314 314 314 314 314 314 314 314 314 315 315 315 315 315 315 315 315 315 20.476 11.346 20.781 11.451 20.990 11.774 18.965 10.470 18.143 9.932 14.335 11.688 14.101 12.879 13.665 10.995 13.870 10.047 12.720 11.659 11.866 10.690 10.908 9.792 9.671 10.432 9.666 11.623 8.694 9.715 13.465 12.489 14.571 12.145 12.855 13.568 11.943 13.768 13.460 14.406 13.182 15.876 14.202 16.886 13.586 18.089 13.940 18.333 12.756 18.772 12.835 14.037 11.606 13.917 13.660 13.816 14.628 13.926 13.156 13.592 13.718 12.317 13.105 11.093 11.907 10.560 11.301 9.445 13.680 10.470 13.085 9.361 -3.081 1.00 12.42 -4.026 1.00 0.00 -2.338 1.00 0.00 -1.542 1.00 17.98 -1.353 1.00 0.00 -079 1.00 0.00v -5.435 1.00 16.16 -5.676 1.00 12.19 -4.505 1.00 13.42 -4.350 1.00 0.00 -3.609 1.00 11-44 -2.822 1.00 8.28 -3.562 1.00 12.05 -4.151 1.00 13.52 -4.445 1.00 17.14 -4.345 1.00 12.82 -2.568 1.00 8.47 -2.119 1.00 10.79 -2.125 1.00 11.58 -2.434 1.00 0.00 -1.119 1.00 17.11 -1.474 1.00 27.79 -0.930 1.00 39.55 -0.219 1.00 47.02 0.940 1.00 45.02 -0.825 1.00 50.75 0.226 1.00 11.85 0.331 1.00 7.93 1.254 1.00 12.01 1.152 1.00 0.00 2.607 1.00 12.93 3.224 1.00 12.89 2.629 1.00 10.77 3.135 1.00 4.78 2.546 1.00 10.51 1.504 1.00 10.84 0.895 1.00 11.24 17.873 9.507 -3.514 1.00 0.00 19.374 10.627 -2.804 1.00 18.47 296 ATOM 2646 CZ PTY 315 11.887 8.828 1.407 1.00 12.06 ATOM 2647 OH PTY 315 11.369 7.695 0.799 1.00 10.74 ATOM 2648 ORi PTY 315 9.804 6.760 -0.809 1.00 19.02 ATOM 2649 0R2 PTY 315 9.041 8.574 0.508 1.00 16.68 ATOM 2650 0R3 PTY 315 9.423 6.511 1.512 1.00 18.31 ATOM 2651 PR PTY 315 9.871 7.408 0.478 1.00 5.42 ATOM 2652 C PTY 315 13.603 14.774 3.451 1.00 12.45 ATOM 2653 0 PTY 315 14.708 15.296 3.294 1.00 12.95 ATOM 2654 N ASP 316 12.738 15.212 4.343 1.00 15.05 ATOM 2655 H ASP 316 11.936 14.675 4.511 1.00 0.00 ATOM 2656 CA ASP 316 13.002 16.360 5.173 1.00 13.90 ATOM 2657 CE ASP 316 11.688 16.931 5.649 1.00 16.18 ATOM 2658 CG ASP 316 10.975 17.923 4.741 1.00 20.73 ATOM 2659 ODi ASP 316 10.924 17.743 3.529 1.00 19.42 ATOM 2660 002 ASP 316 10.443 18.893 5.274 1.00 27.82 .ATOM 2661 C ASP 316 13.866 15.995 6.357 1.00 14.41 ATOM 2662 0 ASP 316 13.970 14.838 6.776 1.00 15.75 ATOM 2663 N VAL 317 14.519 17.004 6.913 1.00 15.30 *ATOM 2664 H VAL 317 14.334 17.922 6.631 1.00 0.00 ATOM 2665 CA VAL 317 15.385 16.846 8.073 1.00 14.94 ATOM 2666 CB VAL 317 16.858 17.146 7.739 1.00 14.44 ATOM 2667 CG1 VAL 317 17.448 15.947 7.004 1.00 15.76 ATOM 2668 CG2 VAL 317 16.981 18.357 6.832 1.00 16.92 ATOM 2669 C VAL 317 14.871 17.842 9.083 1.00 14.10 ATOM 2670 0 VAL 317 14.248 18.845 8.712 1.00 17.30 ATOM 2671 N LEU 318 15.029 17.480 10.349 1.00 12.16 ATOM 2672 H LEU 318 15.548 16.671 10.535 1.00 0.00 ATOM 2673 CA LEU 318 14.624 18.329 11.451 1.00 14.05 ATOM 2674 CB LEU 318 14.818 17.637 12.790 1.00 13.29 ATOM 2675 CG LEU 318 14.067 16.364 13.069 1.00 4.19 ATOM 2676 CD1 LEU 318 14.669 15.703 14.270 1.00 3.04 ATOM 2677 CD2 LEU 318 12.625 16.643 13.287 1.00 2.00 ATOM 2678 C LEU 318 15.537 19.537 11.433 1.00 16.18 ATOM 2679 0 LEU 318 16.665 19.398 10.961 1.00 13.67 ATOM 2680 N ASP 319 15.117 20.707 11.882 1.00 26.49 ATOM 2681 H ASP 319 14.247 20.848 12.302 1.00 0.00 ATOM 2682 CA ASP 319 16.062 21.792 11.942 1.00 34.53 ATOM 2683 CB ASP 319 15.636 22.871 10.880 1.00 39.93 ATOM 2684 CG ASP 319 14.637 23.977 11.210 1.00 46.93 297 S S S. S

S

S.

5 0

S.

S S *5

S

S

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

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ATOM

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ATOM

ATOM

ATOM

ATOM

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2685 ODi ASP 319 2686 0D2 ASP 319 2687 C ASP 319 2688 0 ASP 319 2689 OT ASP 319 2690 CB ASP 1003 2691 CG ASP 1003 2692 ODi ASP 1003 2693 0D2 ASP 1003 2694 C ASP 1003 2695 0 ASP 1003 2696 HT1 ASP 1003 2697 HT2 ASP 1003 2698 N ASP 1003 2699 HT3 ASP 1003 2700 CA ASP 1003 2701 N PRO 1004 2702 CD PRO 1004 2703 CA PRO 1004 2704 CB PRO 1004 2705 CG PRO 1004 2706 C PRO 1004 2707 0 PRO 1004 2708 N ALA 1005 2709 H ALA 1005 2710 CA ALA 1005 2711 CB ALA 1005 2712 C ALA 1005 2713 0 ALA 1005 2714 N ALA 1006 2715 H ALA 1006 2716 CA ALA 1006 2717 CB ALA 1006 2718 c ALA 1006 2719 0 ALA 1006 2720 N HIS 1007 2721 H HIS 1007 2722 CA HIS 1007 2723 CB HIS 1007 13.509 23.928 10.710 1.00 52.84 15.003 24.906 11.941 1.00 52.04 16.064 22.270 13.401 1.00 36.49 14.996 22.586 13.944 1.00 37.04 17.140 22.239 14.004 1.00 36.34 43.142 -13.016 13.156 1.00 53.93 43.106 -12.430 14.568 1.00 55.01 44.109 -11.869 15.uuu 1.00 54.01 42.091 -12.567 15.252 1.00 58.11 44.166 -11.129 11.729 1.00 46.97 45.204 -11.666 11.320 1.00 50.37 44.012 -13.030 10.569 1.00 0.00 42.591 -12.376 9.952 1.00 0.00 42.996 -12.885 10.758 1.00 53.96 42.524 -13.800 10.916 1.00 0.00 42.970 -12.063 11.955 1.00 49.69 44.151 -9.802 11.904 1.00 43.37 42.945 -8.991 12.008 1.00 42.38 45.344 -8.948 11.771 1.00 42.64 44.794 -7.522 11.801 1.00 39.86 43.467 -7.643 12.503 1.00 40.49 46.477 -9.175 12.780 1.00 41.41 47.559 -8.570 12.685 1.00 39.94 46.242 -10.044 13.772 1.00 39.65 45.323 -10.276 14.007 1.00 0.00 47.290 -10.440 14.688 1.00 31.86 46.785 -10.334 16.117 1.00 30.50 47.801 -11.850 14.451 1.00 28.13 48.889 -12.126 14.931 1.00 27.62 47.227 -12.783 13.671 1.00 30.30 46.450 -12.533 13.136 1.00 0.00 47.757 -14.165 13.610 1.00 29.17 46.836 -15.035 12.767 1.00 31.01 49.186 -14.409 13.109 1.00 29.99 49.832 -15.435 13.328 1.00 30.85 49.713 -13.387 12.465 1.00 29.64 49.168 -12.584 12.420 1.00 0.00 51.077 -13.401 11.952 1.00 31.60 51.162 -12.602 10.648 1.00 32.94 55.555

S

S

298 ATOM 2724 CG HIS 1007 50.861 -11.131 1.92 .0367 10.902 1.00 36.73 0@@S

S

S.

S

0S S S

*.SS

.5 S S

SS

S S

S

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S

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*5SS S S 0S S

S

*5@5 500055 0 0

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2725 2726 2727 2728 2729 2730 2731 2732 2733 2734 2735 2736 2737 2738 2739 2740 2741 2742 2743 2744 2745 2746 2747 2748 2749 2750 2751 2752 2753 2754 2755 2756 2757 2758 2759 2760 2761 2762 CD2 ND1 HDi GEl NE2 HE2

C

0

N

H

CA

CB

CG

CD1 CD2

C

0

N

CD

CA

GB

CG

C

0

N

H

CA

GB

CG

CD1 CD2 GEl CE2 Gz

C

0

N

H

HIS

HIS

HIS

HIS

HIS

HIS

HIS

HIS

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

PRO

PRO

PRO

PRO

PRO

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PHE

PHE

PHE

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PE

PHE

PE

PE

PHE

PE

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1007 1007 1007 1007 1007 1007 1007 1007 1008 1008 1008 1008 1008 1008 1008 1008 1008 1009 1009 1009 1009 1009 1009 1009 1010 1010 1010 1010 1010 1010 1010 1010 1010 1010 1010 1010 1011 1011 49.606 -10.560 51.734 -10.193 52.690 -10.342 51.062 -9.078 49.789 -9.313 49.059 -8.678 52.050 -12.781 53.158 -12.386 51.592 -12.480 50.742 -12.852 52.427 -11.828 51.558 -10.849 51.829 -9.348 52.484 -8.962 50.513 -8.620 52.963 -12.958 52.181 -13.829 54.245 -13.032 55.280 -12.055 54.787 -14.159 56.285 -14.047 56.538 -12.546 54.405 -14.163 54.692 -15.112 53.788 -13.089 53.497 -12.388 53.398 -12.960 53.950 -11.636 53.756 -10.406 52.546 -9.728 54.816 -9.958 52.397 -8.599 54.667 -8.827 53.456 -8.142 51.888 -13.006 51.374 -12.658 51.182 -13.399 51.635 -13.830 10. 876 11. 247 11. 446 11. 434 11. 213 11. 422 12.946 12.576 14.151 14.476 15.126 15. 911 1 5.83 5 14.531 16.018 15.979 16.350 16.334 15.973 17.084 16.806 16.691 18.566 19.297 19.060 18 .445 20.459 21.035 20.161 20.140 19.376 19.332 18.567 18.544 20.636 21.699 19.565 1.00 38.63 1.00 39.17 1.00 0.00 1.00 41.04 1.00 40.15 1.00 0.00 1.00 30.36 1.00 31.97 1.00 26.41 1.00 0.00 1.00 24.03 1.00 20.44 1.00 19.01 1.00 15.31 1.00 18.56 1.00 24.31 1.00 21.63 1.00 25.92 1.00 29.07 1.00 26.60 1.00 28.94 1.00 27.11 1.00 24.10 1.00 25.51 1.00 20.53 1.00 0.00 1.00 20.39 1.00 19.73 1.00 16.45 1.00 17.02 1.00 23.44 1.00 21.75 1.00 21.56 1.00 18.10 1.00 20.98 1.00 20.72 1.00 15.13 18.814 1.00 0.00 299 a a a. a.

a a.

a a a a a ATOM 2763 ATOM 2764 ATOM 2765 ATOM 2766 ATOM 2767 ATOM 2768 ATOM 2769 ATOM 2770 ATOM 2771 1 0 ATOM 2772 ATOM 2773 ATOM 2774 ATOM 2775 ATOM 2776 1 5 ATOM 2777 ATOM 2778 ATOM 2779 ATOM 2780 ATOM 2781 ATOM 2782 ATOM 2783 ATOM 2784 ATOM 2785 ATOM 2786 ATOM 2787 ATOM 2788 ATOM 2789 ATOM 2790 ATOM 2791 ATOM 2792 ATOM 2793 ATOM 2794 ATOM 2795 ATOM 2796 ATOM 2797 ATOM 2798 ATOM 2799 ATOM 2800 ATOM 2801 CA PHE 1011 CB PHE 1011 CG PHE 1011 CD1 PHE 1011 CD2 PHE 1011 CEl PHE 1011 CE2 PHE 1011 CZ PHE 1011 C PHE 1011 O PHE 1011 N TYR 1012 H TYR 1012 CA TYR 1012 CB TYR 1012 CG TYR 1012 CD1 TYR 1012 CE1 TYR 1012 CD2 TYR 1012 CE2 TYR 1012 CZ TYR 1012 OH TYR 1012 RH TYR 1012 C TYR 1012 O TYR 1012 N GLY 1013 H GLY 1013 CA GLY 1013 C GLY 1013 O GLY 1013 N SEP. 1014 H SER 1014 CA SER 1014 CB SER 1014 OG SER 1014 HG SEP. 1014 C SEP. 1014 O SER 1014 N ILE 101-5 H ILE 1015 49.748 -13.457 49.224 -13.105 47.716 -13.279 46.856 -12.628 47.200 -14.136 45.488 -12.846 45.824 -14.347 44.974 -13.702 49.413 -14.891 49.963 -15.834 48.496 -15.092 48.085 -14.317 48.204 -16.427 48.456 -16.449 49.930 -16.553 50.738 -15.427 52.086 -15.504 50.464 -17.783 51.820 -17.871 52.612 -16.728 53.929 -16.816 54.334 -15.949 46.821 -16.971 46.537 -18.146 45.948 -16.193 46.199 -15.277 44.602 -16.654 43.768 -16.522 44.088 -15.717 42.692 -17.277 42.460 -17.891 41.790 -17.228 40.446 -17.759 40.140 -17.212 39.581 -16.430 42.335 -18.038 42.025 -19.222 43.242 -17.436 43.553 -16.542 19.564 18.175 18.066 18.960 17. 096 18.889 17. 029 17. 929 19.933 19.365 20.870 21. 306 21.346 22.842 23 .172 23.116 23.417 23.531 23.839 23.782 24.155 23.998 21.048 21. 309 20.413 20.194 20.123 21.380 22.260 21.461 20 .729 22.572 22.077 20.789 20 .875 23.735 23.887 24.506 24.252 1.00 11.64 1.00 9.39 1.00 10.72 1.00 7.85 1.00 9.06 1.00 4.55 1.00 9.37 1.00 7.19 1.00 13.64 1.00 13.56 1.00 13.88 1.00 0.00 1.00 14.06 1.00 13.70 1.00 10.19 1.00 8.33 1.00 11.13 1.00 15.69 1.00 18.91 1.00 17.41 1.00 19.18 1.00 0.00 1.00 14.86 1.00 14.54 1.00 15.74 1.00 0.00 1.00 12.83 1.00 13.78 1.00 12.71 1.00 14.40 1.00 0.00 1.00 19.95 1.00 21.51 1.00 23.00 1.00 0.00 1.00 21.75 1.00 27.85 1.00 22.37 1.00 0.00 300

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

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ATOM

ATOM

ATOM

ATOM

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ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2802 2803 2804 2805 2806 2807 2808 2809 2810 2811 2812 2813 2814 2815 2816 2817 2818 2819 2820 2821 2822 2823 2824 2825 2826 2827 2828 2829 2830 2831 2832 2833 2834 2835 2836 2837 2838 2839 2840

CA

CB

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CD

C

0

N

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HG

C

0

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NH1 HH1 1 HH1 2 NH2 HH2 1 HH2 2

C

0

N

H

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ILE 1015 ILE 1015 ILE 1015 ILE 1015 ILE 1015 ILE 1015 ILE 1015 SE( 10U16 SER 1016 SER 1016 SER 1016 SER 1016 SER 1016 SER 1016 SER 1016 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ARG 1017 ALA 1018 ALA 1018 ALA 1018 ALA 1018 ALA 1018 ALA 1018 GLU 1019 43.755 -18.030 45.300 -17.928 45.816 -18.827 45.828 -16.508 47.306 -16.402 43.133 -17.261 42.731 -16.114 43.011 -1 7 .835 43.360 -18.737 42.414 -17.128 41.797 -18.106 42.766 -19.003 42.913 -19.673 43.474 -16.305 44.662 -16.478 43.088 -15.451 42.137 -15.409 44.027 -14.653 43.262 -13.808 44.157 -12.902 43.366 -12.149 42.474 -11.197 42.024 -11.439 42.184 -10.026 42.697 -9.643 43.328 -10.244 42.461 -8.748 41.347 -9.228 40.952 -9.522 41.112 -8.334 45.001 -15.567 46.202 -15.294 44.481 -16.675 43.505 -16.792 45.274 -17.667 44.380 -18.824 46.356 -18.208 47.521 -18.209 46.018 -18.541 25.737 25.823 24.712 25.738 26.087 26.894 26.688 28 .091 28.240 29.211 30.225 30.737 30.056 29.907 29.609 30.866 31. 087 31.653 32.672 33.519 34.570 33.952 33.117 34.498 35.658 36.148 36.037 33.854 32.984 34.236 32.383 32.469 32.906 32 .879 33.611 34.070 32.707 33.097 31.453 1.00 18.94 1.00 14.49 1.00 10.66 1.00 5.38 1.00 4.01 1.00 18.07 1.00 15.23 .00U .L7.6 1.00 0.00 1.00 17.39 1.00 13.17 1.00 18.24 1.00 0.00 1.00 15.97 1.00 20.64 1.00 18.56 1.00 0.00 1.00 16.01 1.00 17.86 1.00 10.59 1.00 8.03 1.00 11.62 1.00 0.00 1.00 13.10 1.00 14.59 1.00 0.00 1.00 0.00 1.00 15.19 1.00 0.00 1.00 0.00 1.00 16.72 1.00 22.39 1.00 21.82 1.00 0.00 1.00 19.48 1.00 18.63 1.00 20.25 1.00 23.41 1.00 26.17 301 a a

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2841 2842 2843 2844 2845 2846 2847 2848 2849 2850 2851 2852 2853 2854 2855 2856 2857 2858 2859 2860 2861 2862 2863 2864 2865 2866 2867 2868 2869 2870 2871 2872 2873 2874 2875 2876 2877 2878 H GLU CA GLU CB GLU CG GLU CD GLU OE1 GU 0E2 GLU C GLU 0 GLU N ALA H ALA CA ALA CB ALA C ALA o ALA N GLU H GU CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU o GLU N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GU C GLU o GLU N HIS H HIS CA HIS 1019 1019 1019 1019 1019 1019 1019 1019 1019 1020 1020 1020 1020 1020 1020 1021 1021 1021 1021 1021 1021 1021 1021 1021 1021 1022 1022 1022 1022 1022 1022 1022 1022 1022 1022 1023 1023 1023 45.097 -18.382 47.007 -19.117 46.331 -19.816 47.353 -20.841 46.940 -21.712 45.954 -22.447 47.618 -21.681 47.976 -18.080 49.125 -18.401 47.535 -16.831 46.592 -16.654 48.372 -15.704 47.532 -14.431 49.424 -15.451 50.621 -15.470 48.992 -15.301 48.029 -15.342 49.877 -15.110 49.070 -14.931 48.343 -13.605 47.521 -13.292 47.081 -12.150 47.303 -14.160 50.831 -16.271 51.999 -16.024 50.422 -17.533 49.465 -17.718 51.361 -18.649 50.708 -20.001 49.564 -20.417 49.750 -20.078 50.608 -20.686 49.036 -19.195 52.488 -18.469 53.647 -18.612 52.147 -18.072 51.192 -17.931 53.099 -17.785 52.402 -17.389 31.148 30.559 29.366 28.796 27. 601 27.709 26. 568 3 0.045 29.708 29.929 3 0.134 29.515 29.359 30.587 30.283 31. 843 32.004 32.982 34.246 34.247 35.485 35.589 36.338 33.181 33 .469 32.999 32.877 33.072 32.767 33.691 35.168 35.813 35.663 32.080 32.469 30.835 30.660 29.768 28.463 1.00 0.00 1.00 25.54 1.00 32.42 1.00 48.31 1.00 54.58 1.00 61.36 1.00 56.27 1.00 20.28 1.00 22.96 1.00 20.31 1.00 0.00 1.00 14.33 1.00 10.33 1.00 17.38 1.00 20.66 1.00 20.59 1.00 0.00 1.00 23.11 1.00 22.53 1.00 17.51 1.00 22.86 1.00 26.96 1.00 31.30 1.00 22.56 1.00 24.82 1.00 26.01 1.00 0.00 1.00 28.78 1.00 32.14 1.00 41.37 1.00 47.97 1.00 50.55 1.00 51.22 1.00 29.05 1.00 30.51 1.00 29.07 1.00 0.00 1.00 23.70 1.00 26.84 ATOM 2879 CB HIS 1023 302 ATOM 2880 CG HIS 1023 51.754 -18.539 27.700 1.00 21.08 ATOM 2881 CD2 HIS 1023 52.452 -19.570 27.112 1.00 19.12 ATOM 2882 ND1 HIS 1023 50.457 -18.741 27.451 1.00 18.71 ATOM 2883 HD1 HIS 1023 49.706 -18.258 27.867 1.00 0.00 ATOM 2884 CEl HIS 1023 50.345 -19.836 26.738 1.00 15.87 ATOM 2885 NE2 HIS 1023 51.548 -20.329 26.541 1.00 17.83 ATOM 2886 HE2 HIS 1023 51.752 -21.134 26.020 1.00 0.00 ATOM 2887 c HIS 1023 54.043 -16.662 30.107 1.00 20.78 ATOM 2888 0 HIS 1023 55.247 -16.815 29.895 1.00 24.83 ATOM 2889 N LEU 1024 53.578 -15.531 30.628 1.00 22.60 ATOM 2890 H LEU 1024 52.612 -15.418 30.757 1.00 0.00 ATOM 2891 CA LEU 1024 54.489 -14.462 31.036 1.00 24.27 ATOM 2892 CB LEU 1024 53.753 -13.210 31.558 1.00 24.96 ATOM 2893 CG LEU 1024 53.085 -12.073 30.735 1.00 22.86 ATOM 2894 CD1 LEU 1024 53.723 -12.000 29.373 1.00 19.34 *ATOM 2895 CD2 LEU 1024 51.605 -12.301 30.571 1.00 18.19 ATOM 2896 c LEU 1024 55.404 -14.940 32.163 1.00 28.32 ATOM 2897 0 LEU 1024 56.605 -14.641 32.186 1.00 30.07 ATOM 2898 N LYS 1025 54.863 -15.712 33.115 1.00 33.91 ATOM 2899 H LYS 1025 53.911 -15.931 33.060 1.00 0.00 SATOM 2900 CA LYS 1025 55.640 -16.233 34.239 1.00 35.35 ATOM 2901 CB LYS 1025 54.782 -17.080 35.183 1.00 38.19 ATOM 2902 CG LYS 1025 53.976 -16.173 36.102 1.00 40.50 **ATOM 2903 CD LYS 1025 53.101 -16.863 37.152 1.00 42.76 25 ATOM 2904 CE LYS 1025 51.986 -17.672 36.534 1.00 40.89 ATOM 2905 NZ LYE 1025 51.138 -18.245 37.560 1.00 45.64 ATOM 2906 HZ1 LYS 1025 50.393 -18.818 37.119 1.00 0.00 ATOM 2907 HZ2 LYE 1025 50.696 -17.477 38.105 1.00 0.00 ATOM 2908 HZ3 LYS 1025 51.705 -18.843 38.193 1.00 0.00 ATOM 2909 C LYE 1025 56.770 -17.090 33 .731 1.00 34.63 ATOM 2910 0 LYE 1025 57.936 -16.854 34.046 1.00 36.50 ATOM 2911 N LEU 1026 56.426 -18.031 32.857 1.00 37.51 ATOM 2912 H LEU 1026 55.483 -18.128 32.621 1.00 0.00 ATOM 2913 CA LEU 1026 57.402 -18.908 32.245 1.00 35.08 ATOM 2914 CB LEU 1026 56.671 -19.965 31.406 1.00 35.34 ATOM 2915 CG LEU 1026 55.672 -20.873 32.167 1.00 34.52 ATOM 2916 CD1 LEU 1026 55.241 -22.004 31.260 1.00 34.74 ATOM 2917 CD2 LEU 1026 56.297 -21.471 33.418 1.00 31.16 ATOM 2918 c LEU 1026 58.388 -18.115 31.408 1.00 34.31 303 ATOM 2919 0 LEU 1026 59.576 -18.431 31.418 1.00 37.02 ATOM 2920 N ALA 1027 58.007 -17.022 30.749 1.00 36.27 ATOM 2921 H ALA 1027 57.062 -16.764 30.756 1.00 0.00 ATOM 2922 CA ALA 1027 58.969 -16.177 30.032 1.00 38.06 ATOM 2923 CB ALA 1027 58.185 -15.258 29.091 1.00 39.20 ATOM 2924 C ALA 1027 59.879 -15.327 30.956 1.00 40.05 ATOM 2925 0 ALA 1027 60.436 -14.291 30.568 1.00 42.49 ATOM 2926 1GLT 102 60o A.042 -15C. 70l1 32 .220a I n A I .21 ATOM 2927 H GLY 1028 59.563 -16.479 32.578 1.00 0.00 1 0 ATOM 2928 CA GLY 1028 60.911 -15.002 33.146 1.00 41.60 ATOM 2929 c GLY 1028 60.320 -13.705 33.688 1.00 42.47 ATOM 2930 0 GLY 1028 61.123 -12.858 34.082 1.00 45.26 ATOM 2931 N MET 1029 58.999 -13.445 33.704 1.00 39.68 *ATOM 2932 H MET 1029 58.405 -14.085 33.254 1.00 0.00 1. ATOM 2933 CA MET 1029 58.415 -12.229 34.296 1.00 39.81 :::ATOM 2934 CB MET 1029 58.204 -12.492 35.780 1.00 37.74 ATOM 2935 CG MET 1029 57.191 -13.558 36.080 1.00 34.82 ATOM 2936 SD MET 1029 55.548 -13.160 35.465 1.00 37.33 ATOM 2937 CE MET 1029 55.139 -11.863 36.592 1.00 28.27 ATOM 2938 c MET 1029 59.106 -10.850 34.145 1.00 41.56 *ATOM 2939 0 MET 1029 58.930 -9.913 34.953 1.00 43.62 ATOM 2940 N ALA 1030 59.892 -10.700 33.074 1.00 41.39 ATOM 2941 H ALA 1030 59.990 -11.464 32.474 1.00 0.00 ATOM 2942 CA ALA 1030 60.625 -9.484 32.791 1.00 39.08 25 ATOM 2943 CB ALA 1030 61.401 -9.669 31.495 1.00 37.10 ATOM 2944 C ALA 1030 59.718 -8.269 32.674 1.00 40.79 ATOM 2945 0 ALA 1030 58.540 -8.363 32.315 1.00 39.87 ATOM 2946 N ASP 1031 60.262 -7.100 32.994 1.00 43.06 ATOM 2947 H ASP 1031 61.220 -7.054 33.170 1.00 0.00 ATOM 2948 CA ASP 1031 59.483 -5.883 32.928 1.00 46.24 ATOM 2949 CB ASP 1031 60.222 -4.768 33 .674 1.00 50.38 ATOM 2950 CG ASP 1031 59.322 -3.657 34.202 1.00 52.70 ATOM 2951 ODi ASP 1031 59.536 -3.217 35.330 1.00 55.84 ATOM 2952 0D2 ASP 1031 58.406 -3.232 33.502 1.00 54.94 ATOM 2953 C ASP 1031 59.342 -5.564 31.446 1.00 45.89 ATOM 2954 0 ASP 1031 60.282 -5.798 30.682 1.00 48.59 ATOM 2955 N GLY 1032 58.159 -5.114 31.029 1.00 45.12 ATOM 2956 H GLY 1032 57.428 -5.032 31.670 1.00 0.00 ATOM 2957 CA GLY 1032 57.872 -4.794 29.638 1.00 39.58 304 ATOM 2958 C GLY 1032 57.597 -6.031 28.788 1.00 37.39

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

2959 2960 2961 2962 2963 2964 2965 2966 2967 2968 2969 2970 2971 2972 2973 2974 2975 2976 2977 2978 2979 2980 2981 2982 2983 2984 2985 2986 2987 2988 2989 2990 2991 2992 2993 2994 2995 2996

O

N

H

CA

CB

CG

CD1 CD2

C

O

N

H

CA

CB

CG

CD1 CD2 CE1 CE2

CZ

C

0

N

H

CA

CB

CG

CD1 CD2

C

O

N

H

CA

CB

CG

CD1 CD2 GLY 1032 LEU 1033 LEU 1033 LEU 1033 LEU 1033 LEU 1033 LEU 1033 LEU 1033 LEU 1033 LEU 1033 PHE 1034 PHE 1034 PHE 1034 PHE 1034 PHE 1034 PHE 1034 PHE 1034 PHE 1034 PHE 1034 PHE 1034 PHE 1034 PHE 1034 LEU 1035 LEU 1035 LEU 1035 LEU 1035 LEU 1035 LEU 1035 LEU 1035 LEU 1035 LEU 1035 LEU 1036 LEU 1036 LEU 1036 LEU 1036 LEU 1036 LEU 1036 LEU 1036 57.438 -5.940 57.585 -7.218 57.724 -7.251 57.259 -8.459 57.502 -9.640 57.337 -11.085 58.468 -11.545 57.322 -11.918 55.776 -8.298 55.029 -7.838 55.363 -8.589 56.006 -8.911 53.976 -8.439 53.761 -7.092 54.457 -6.953 53.722 -7.110 55.818 -6.664 54.343 -6.983 56.436 -6.534 55.702 -6.694 53.571 -9.571 54.417 -10.319 52.284 -9.686 51.633 -9.098 51.775 -10.647 51.654 -12.048 50.695 -12.462 49.314 -12.804 51.181 -13.777 50.415 -10.122 49.817 -9.268 49.905 -10.668 50.390 -11.397 48.602 -10.296 48.862 -9.725 47.848 -8.867 47.484 -7.615 48.479 -8.470 27.563 29.397 30.367 28.716 29.646 29.224 28.347 30.487 28.427 29.302 27.198 26.529 26.822 26.100 24.744 23.570 24.665 22.333 23.422 22.259 25.908 25.405 25.641 26.081 24.685 25.333 26.447 25.946 26.987 24.256 24.938 23.154 22.713 22.636 21.252 20.504 21.281 19.168 1.00 36.99 1.00 33.89 1.00 0.00 1.00 28.02 1.00 26.51 1.00 22.78 1.00 18.85 1.00 19.74 1.00 26.53 1.00 23.41 1.00 24.15 1.00 0.00 1.00 21.19 1.00 21.77 1.00 23.54 1.00 27.19 1.00 24.54 1.00 25.67 1.00 24.17 1.00 24.71 1.00 20.13 1.00 20.20 1.00 21.17 1.00 0.00 1.00 19.77 1.00 20.30 1.00 12.94 1.00 14.01 1.00 12.52 1.00 18.47 1.00 13.42 1.00 17.71 1.00 0.00 1.00 17.41 1.00 15.80 1.00 21.02 1.00 12.72 1.00 21.07 305

ATOM

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ATOM

ATOM

ATOM

ATOM

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ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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1 5 ATOM

ATOM

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ATOM

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25 ATOM

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2997 2998 2999 3000 3001 3002 3003 3004 3005 3006 3007 3008 3009 3010 3011 3012 3013 3014 3015 3016 3017 3018 3019 3020 3021 3022 3023 3024 3025 3026 3027 3028 3029 3030 3031 3032 3033 3034 3035

C

0

N

H

CA

CB

CG

CD

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Cz NH1 HH11 iHI2 NH2 iH21 iH2 2

C

0

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CA

CB

CG

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OE1 NE2 iE21 {E22

C

0

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CA

CB

SG

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0

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LEU 1036 LEU 1036 ARG 1037 ARG 1037 ARG 1037 ARG 1037 ARG 1037 ARG 1037 ARG 1037 ARG 1037 ARG 1037 ARG 1037 ARG 1037 ARG 1037 ARG 1037 ARG 1037 ARG 1037 ARG 1037 ARG 1037 GLN 1038 GLN 1038 GLN 1038 GLN 1038 GLN 1038 GLN 1038 GLN 1038 GLN 1038 GLN 1038 GLN 1038 GLN 1038 GLN 1038 CYS 1039 CYS 1039 CYS 1039 CYS 1039 CYS 1039 CYS 1039 CYS 1039 LEU 1040 47.675 -11.526 48.100 -12.643 46.401 -11.417 46.037 -10.536 45.486 -12.558 45.303 -13.143 44.799 -12.232 44.980 -13.004 45.018 -12.174 45.850 -11.703 43.963 -12.015 42.788 -12.578 42.647 -13.162 42.038 -12.409 44.111 -11.263 45.000 -10.842 43.362 -11.129 44.144 -12.076 43.870 -10.880 43.274 -12.913 43.461 -13.872 41.997 -12.454 41.373 -13.521 40.006 -13.156 39.307 -14.246 38.715 -15.187 39.311 -14.134 39.718 -13.321 38.909 -14.848 41.101 -12.214 41.119 -13.003 40.296 -11.154 40.277 -10.599 39.372 -10.872 38.926 -9.451 37.883 -8.919 38.179 -11.826 37.519 -12.057 37.900 -12.406 22.636 22.317 23.034 23.270 23.011 24.403 25.502 26.799 27.995 28.210 28.790 28.579 27.780 29.219 29.863 30.042 30.503 22.487 22.529 21.947 21.999 21.426 20.540 19.989 19.187 19.728 17.871 17.496 17.342 22.617 23.573 22.554 21.746 23.623 23.477 24.843 23.602 22.579 24.768 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 15.31 14.62 14.85 0.00 14.73 12.40 11.81 18.91 13.00 0.00 8.56 4.18 0.00 0.00 15.54 0.00 0.00 15.15 18.16 15.48 0.00 14.10 18.15 28.15 34.24 38.06 37.72 0.00 0.00 16.07 18.21 12.03 0.00 13 .04 9.29 18.16 14.04 14.09 15.22 306

S

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1 5 ATOM

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3046 3047 3048 3049 3050 3051 3052 3053 3054 3055 3056 3057 3058 3059 3060 3061 3062 3063 3064 3065 3066 3067 3068 3069 3070 3071 3072 3073 3036 3037 3038 3039 3040 3041 3042 3043 3044 3045 H LEU 1040 CA LEU 1040 CB LEU 1040 CG LEU 1040 CD1 LEU 1040 CD2 LEU 1040 C LEU 1040 LEU 1040 N ARG 1041 H ARG 1041 CA ARC 1041 CB ARG 1041 CG ARG 1041 CD ARG 1041 NE ARG 1041 HE ARC 1041 CZ ARG 1041 NHi ARG 1041 HH11 ARG 1041 HH12 ARG 1041 NH2 ARG 1041 HH21 ARC 1041 HH22 ARG 1041 C ARC 1041 o ARG 1041 N SEP. 1042 H SEP. 1042 CA SEP. 1042 CS SEP. 1042 OC SEP. 1042 HG SEP. 1042 C SEP. 1042 O SEP. 1042 N LEU 1043 H L EU1 1043 CA LEU 1043 CB LEC 1043 CG LEU 1043 38.502 -12.212 36.787 -13.319 37.085 -14.214 37.745 -15.585 38.554 -15.722 38.561 -15.784 35.454 -12.620 34.418 -13.274 35.377 -11.311 36.187 -10.764 34.111 -10.669 34.288 -9.748 35.011 -10.409 35.147 -9.425 36.250 -8.523 37.154 -8.890 36.099 -7.224 34.902 -6.630 34.070 -7.163 34.836 -5.648 37.194 -6.525 38.088 -6.972 37.125 -5.546 33.576 -9.862 32.381 -9.559 34.423 -9.463 35.377 -9.669 33.974 -8.656 34.508 -7.256 35.923 -7.314 36.266 -6.507 34.426 -9.212 35.579 -9.627 33.518 -9.265 32.600 -9.025 33.811 -9.648 32.509 -9.609 31.223 -10.342 30.091 -10.041 25 .526 24.969 26.168 2 6.056 24.770 27.339 25.195 25.228 25.374 25.346 25.679 26.874 28.044 29.170 28.926 28.998 28.699 28.678 28.831 28.501 28.474 28.482 28.291 24.520 24.485 23 .581 23.602 22.476 22.661 22.764 23 .176 21. 146 21. 026 20.173 20.392 18.798 17.961 18.414 17.441 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 i.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1. 00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0.00 9.91 12.52 11. 84 13 .81 13 .23 11.13 13 .17 12 .13 0.00 10.99 12.91 15.73 18.18 19.90 0.00 14.29 18 .27 0.00 0.00 14.40 0.00 0.00 13 .52 14.23 15 .67 0.00 20.42 25.01 29.54 0.00 21.18 25 .17 19. 97 0.00 24.42 24 .11 26.18 20.08 ATOM 3074 CD1 LEU 1043 307 ATOM 3075 CD2 LEU 1043 31.458 -11.837 a a a

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15 ATOM

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3076 3077 3078 3079 3080 3081 309 82 3083 3084 3085 3086 3087 3088 3089 3090 3091 3092 3093 3094 3095 3096 3097 3098 3099 3100 3101 3102 3103 3104 3105 3106 3107 3108 3109 3110 3111 3112 3113 C LEU O LEU N GLY H GLY CA GLY C GLY 0J GL N GLY H GLY CA GLY C GLY o GLY N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CEl TYR CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR C TYR o TYR N VAL H VAL CA VAL CB VAL CG1 VAL CG2 VAL C VAL o VAL N LEU H LEU CA LEU CB LEU 1043 1043 1044 1044 1044 1044 1045 1045 1045 1045 1045 1046 1046 1046 1046 1046 1046 1046 1046 1046 1046 1046 1046 1046 1046 1047 1047 1047 1047 1047 1047 1047 1047 1048 1048 1048 36.996 38.082 7 Ldft 37.935 37.152 38.959 40.081 40.034 41.082 40.988 42.234 43 .490 43 .413 43.708 43 .609 43 .023 42.924 43.217 43 .118 42.631 42 .491 41.744 43 .467 43.984 43.835 43.330 43.721 41.820 45.362 45.953 45.977 45 .429 47.427 47 .865 -8.377 -7.770 7.3916 -7.661 -8.068 -7.050 -8.005 -9.226 -7.446 -6.507 -8.182 -7.848 -8 .275 -9.590 -9.958 -7.327 -7.693 -8.998 -9.302 -8.575 -7.793 -6.969 -8.354 -9.086 -7.929 -8.920 -8.413 -8 .948 -7 .937 -8.849 -6.880 -6.147 -6.758 -5.299 34.852 -8.703 34.643 -7.491 36.012 -9.201 36.200 -10.150 18.459 1.00 27.15 18.164 1.00 23.94 18.066 1.00 27.05 17.770 1.00 24.33 17.951 1.00 0.00 17.087 1.00 22.34 17.961 1.00 22.83 17.4 u 1,00 I Al cu 19.282 1.00 22.47 19.709 1.00 0.00 20.113 1.00 17.57 20.519 1.00 17.34 20.291 1.00 17.24 21.183 1.00 13.57 21.467 1.00 0.00 21.672 1.00 15.71 20.902 1.00 21.28 19.457 1.00 24.29 19.084 1.00 22.08 17.742 1.00 29.88 18.518 1.00 23.41 17.184 1.00 32.25 16.801 1.00 31.62 15.457 1.00 31.31 15.048 1.00 0.00 23.112 1.00 13.63 23.620 1.00 14.97 23.828 1.00 16.06 23.428 1.00 0.00 25.178 1.00 15.04 26.310 1.00 12.79 27.705 1.00 5.01 26.381 1.00 3.47 25.119 1.00 15.77 24.517 1.00 10.22 25.663 1.00 19.22 26.016 1.00 0.00 25.804 1.00 20.69 25.610 1.00 24.41 308

S

55..

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15 ATOM

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3114 3115 3116 3117 3118 3119 3120 3121 3122 3123 3124 3125 3126 3127 3128 3129 3130 3131 3132 3133 3134 3135 3136 3137 3138 3139 3140 3141 3142 3143 3144 3145 3146 3147 3148 3149 3150 3151 3152 0 LEU N SER H SER CA SER CB SER OG SER HG SER C SER O SER N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N VAL H VAL CA VAL CB VAL CG1 VAL CG2 VAL C VAL O VAL N HIS H HIS CA HIS CB HIS CG HIS CD2 HIS ND1 HIS HD1 HIS CEl HIS 1048 1049 1049 1049 1049 1049 1049 1049 1049 1050 1050 1050 1050 1050 1050 1050 1050 1050 1051 1051 1051 1051 1051 1051 1051 1051 1052 1052 1052 1052 1052 1052 1052 1052 1052 CG LEU 1048 CD1 LEU 1048 CD2 LEU 1048 C LEU 1048 49.229 -4.886 50.347 -5.852 49.106 -4.886 47.754 -7.185 47.194 -6.597 48.578 -8.212 48.977 -8.679 48.975 -8.629 48.671 -10.116 47.253 -10.292 47.044 -10.337 50. 465 51. 279 50.806 50. 116 52.137 51.960 52.540 54.012 51.830 52.561 51.730 53 .860 54.494 54.401 55 .474 55.903 54.926 55.091 55. 879 54.811 54.198 55.526 54.622 55.292 56 .403 54.920 54 .229 55.751 -8.350 -8.800 -7.549 -7.296 -7.031 -5.562 -4.304 -4.129 -3.120 -7.280 -7.499 -7.287 -7 .177 -7 .422 -8.537 -8.689 -9.868 -6.086 -5.549 -5.468 -5.900 -4.270 -3.054 -1.796 -1.215 -1.038 -1.225 -0.028 25.045 25.414 23.533 27.239 28.175 27.451 26.690 28.776 28.985 28.987 28.034 28.857 28.051 29.843 30.492 30.060 29.602 30.228 29.911 29.611 31.529 32.430 31.806 31. 065 33 .150 33.264 34.701 32.830 33.424 32.634 34.551 35.181 34.925 34.980 35.514 34.957 36.542 37 .214 36.615 1.00 24.96 1.00 25.43 1.00 30.87 1.00 19.53 1.00 20.94 1.00 18.81 1.00 0.00 1.00 19.55 1.00 13.59 1.00 12.90 1.00 0.00 1.00 23.25 1.00 27.44 1.00 29.25 1.00 0.00 1.00 28.57 1.00 24.11 1.00 25.47 1.00 25.51 1.00 27.22 1.00 30.12 1.00 28.70 1.00 31.79 1.00 0.00 1.00 34.62 1.00 34.04 1.00 36.53 1.00 35.98 1.00 38.18 1.00 35.79 1.00 42.38 1.00 0.00 1.00 46.55 1.00 47.71 1.00 51.97 1.00 50.95 1.00 53 .03 1.00 0.00 1.00 52.41 309 ATOM 3153 ATOM 3154 ATOM 3155 ATOM 3156 ATOM 3157 ATOM 3158 ATOM 3159 ATOM 3160 ATOM 3161 1 0 ATOM 3162 ATOM 3163 ATOM 3164 ATOM 3165 ATOM 3166 1 5 ATOM 3167 ATOM 3168 ATOM 3169 ATOM 3170 ATOM 3171 ATOM 3172 ATOM 3173 ATOM 3174 ATOM 3175 ATOM 3176 25 ATOM 3177 ATOM 3178 ATOM 3179 ATOM 3180 ATOM 3181 ATOM 3182 ATOM 3183 ATOM 31841 ATOM 3185 ATOM 3186 ATOM 3187 ATOM 31881 ATOM 3189 ATOM 3190 ATOM 3191

NE:

HE2

C

0

N

H

CA

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CG

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C

0

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CG

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Cz NH1 ~iH11 4H1 2 NH2 iH2l iH2 2

C

0

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HIS 1052 HIS 1052 HIS 1052 HIS 1052 ASP 1053 ASP 1053 ASP 1053 ASP 1053 ASP 1053 ASP 1053 ASP 1053 ASP 1053 ASP 1053 VAL 1054 VTAL 1054 VAL 1054 VAL 1054 VAL 1054 VAL 1054 VAL 1054 VAL 1054 ARG 1055 ARG 1055 ARG 1055 ARG 1055 ARG 1055 ARG 1055 ARG 1055 ARG 1055 ARG 1055 ARG 1055 ARG 1055 ARG 1055 ARG 1055 ARG 1055 ARG 1055 ARG 1055 ARC 1055 PHE 1056 56.637 -0.145 57.240 0.580 55.905 -4.696 55.023 -4.788 57.194 -5.005 57.743 -4.973 57.851 -5.483 58.239 -4.287 57.191 -3.278 57.343 -2.104 56.244 -3.647 57.098 -6.535 56.537 -6.320 57.101 -7.737 57.591 -7.850 56.472 -8.926 57.278 -9.313 56.979 -10.757 58.788 -9.253 54.953 -8.767 54.305 -9.578 54.297 -7.760 54.798 -7.059 52.851 -7.588 52.474 -6.272 52.105 -6.377 51.635 -5.024 52.729 -4.130 53.219 -4.311 53.110 -3.071 52.525 -2.744 51.767 -3.294 52.844 -1.945 54.075 -2.287 54.496 -2.495 54.380 -1.490 52.273 -7.553 52.702 -6.718 S1.277 -8.400 35.657 35.383 36.308 37.157 36.440 35.634 37.655 38.603 39.068 38.741 39.761 38.462 39.534 37.882 37.043 38.449 39.763 40.164 39.532 38.693 39.358 3 8.117 37.658 38.236 38.916 40.387 40.913 41. 282 42.112 40.553 39.394 39 .044 38.882 41.039 41.922 40.518 36.837 36.031 36. 577 1.00 52.66 1.00 0.00 1.00 48.34 1.00 50.78 1.00 51.11 1.00 0.00 1.00 54.60 1.00 57.17 1.00 55.92 1.00 58.38 1.00 55.18 1.00 54.40 1.00 56.76 1.00 51.08 1.00 0.00 1.00 45.93 1.00 46.32 1.00 48.05 1.00 42.02 1.00 43.30 1.00 39.79 1.00 44.36 1.00 0.00 1.00 44.68 1.00 50.69 1.00 57.61 1.00 61.91 1.00 68.12 1.00 0.00 1.00 69.52 1.00 69.57 1.00 0.00 1.00 0.00 1.00 69.36 1.00 0.00 1.00 0.00 1.00 39.48 1.00 35.41 1.00 35.03 310 ATOM 3192 H PHE 1056 50.896 -8.907 37.325 1.00 0.00 ATOM 3193 CA PHE 1056 50.643 -8.531 35.270 1.00 30.23 ATOM 3194 CB PHE 1056 49.910 -9.817 35.090 1.00 28.55 ATOM 3195 CG PHE 1056 50.728 -11.041 35.334 1.00 24.98 ATOM 3196 CD1 PHE 1056 50.515 -11.749 36.513 1.00 25.55 ATOM 3197 CD2 PHE 1056 51.617 -11.476 34.365 1.00 20.60 ATOM 3198 CEl PHE 1056 51.206 -12.935 36.721 1.00 27.31 ATOM 3199 CE2 PHE 1056 52.305 -12.661 34.579 1.00 25.47 ATOM 3200 CZ PHE 1056 52.099 -13.388 35.751 1.00 27.08 ATOM 3201 c PHE 1056 49.584 -7.487 35.083 1.00 26.03 *ATOM 3202 o PHE 1056 48.861 -7.198 36.038 1.00 28.66 ****ATOM 3203 N HIS 1057 49.427 -6.944 33.888 1.00 23.48 **ATOM 3204 H HIS 1057 49.959 -7.281 33.131 1.00 0.00 :***ATOM 3205 CA HIS 1057 48.428 -5.900 33 .635 1.00 27.72 1 ATOM 3206 CB HIS 1057 49.127 -4.511 33 .499 1.00 27.65 ATOM 3207 CG HIS 1057 49.975 -4.158 34.715 1.00 26.44 0000 ATOM 3208 CD2 HIS 1057 51.296 -4.523 34.820 1.00 26.73 ::*ATOM 3209 ND1 HIS 1057 49.638 -3.584 35.870 1.00 26.22 ATOM 3210 HD1 HIS 1057 48.729 -3.352 36.167 1.00 0.00 O.:o 20 ATOM 3211 CEl HIS 1057 50.693 -3.611 36.650 1.00 23.17 ::.ATOM 3212 NE2 HIS 1057 51.689 -4.182 36.017 1.00 22.82 ATOM 3213 HE2 HIS 1057 52.470 -4.597 36.455 1.00 0.00 ATOM 3214 c HIS 1057 47.737 -6.298 32.332 1.00 26.04 ATOM 3215 o HIS 1057 48.401 -6.849 31.445 1.00 26.55 ATOM 3216 N HIS 1058 46.422 -6.107 32 .193 1.00 23.29 ATOM 3217 H HIS 1058 45.925 -5.566 32.839 1.00 0.00 ATOM 3218 CA HIS 1058 45.668 -6.592 31.043 1.00 17.86 ATOM 3219 CB HIS 1058 44.669 -7.714 31.412 1.00 17.03 ATOM 3220 CG HIS 1058 45.393 -8.892 32.027 1.00 12.01 ATOM 3221 CD2 HIS 1058 45.577 -9.067 33 .378 1.00 14.01 ATOM 3222 ND1 HIS 1058 46.059 -9.845 31.407 1.00 15.39 ATOM 3223 HD1 HIS 1058 46.150 -9.979 30.433 1.00 0.00 ATOM 3224 CEl HIS 1058 46.656 -10.577 32 .308 1.00 18.06 ATOM 3225 NE2 HIS 1058 46.362 -10.102 33.495 1.00 14.69 ATOM 3226 HE2 HIS 1058 46.704 -10.441 34.346 1.00 0.00 ATOM 3227 C HIS 1058 44.872 -5.433 30.553 1.00 14.50 ATOM 3228 0 HIS 1058 44.041 -4.949 31.314 1.00 16.31 ATOM 3229 N PHE 1059 45.101 -4.956 29.343 1.00 16.76 ATOM 3230 H PHE 1059 45.771 -5.375 28.760 1.00 0.00 311 ATOM 3231 CA PHE 1059 ATOM 323 CA EE 059 44.326 -3.837 28.839 1.00 19.96 .00

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20 ATOM

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3232 3233 3234 3235 3236 3237 3238 3239 3240 3241 3242 3243 3244 3245 3246 3247 3248 3249 3250 3251 3252 3253 3254 3255 3256 3257 3258 3259 3260 3261 3262 3263 3264 3265 3266 3267 3268 3269 CB PE CG PHE CD1 PE CD2 PE CE1 PE CE2 PHE CZ PE C PE O PE N PRO CD PRO CA PRO CB PRO CG PRO C PRO O PRO N ILE H ILE CA ILE CB ILE CG2 ILE CGI ILE CD ILE C ILE o ILE N GLU H GLU CA GLU CB GLU CG GLU CD GLtJ OE2. GLU 0E2 GLU C GLU o GLU N ARG H ARG C! ARG 1059 1059 1059 1059 1059 1059 1059 1059 1059 1060 1060 1060 1060 1060 1060 1060 1061 1061 1061 1061 1061 1061 1061 1061 1061 1062 1062 1062 1062 1062 1062 1062 1062 1062 1062 1063 1063 1063 45.215 46.192 47.284 46.007 48.194 46.932 48 .014 43 .564 44.160 42.240 41.428 41.428 39.998 40 .122 41 .767 42.169 41.617 41.291 41. 815 42.985 42.986 44.285 45.456 40.466 39.996 39.804 40.243 38.499 37.689 37. 527 36.164 35.889 35.378 38.743 39.729 37.832 37.039 37.857 -2.681 -2.226 -3.039 -0.976 -2.599 -0.550 -1.354 -4.334 900 -4.224 -3 .723 -4.568 -4 .422 -4.448 -3 .632 -2 .482 -4.135 -5.059 -3.388 -3.990 -3 .497 -3.620 -4.517 -3.649 -4 .775 -2 .541 -1.681 -2 .520 -1.410 -1.439 -1.951 -3 .143 -1.148 -2 .217 -1.570 -2.696 -3.150 -2.429 28.409 29.477 29.834 30. 070 30.785 31.023 31.378 27.628 26.703 27.616 28.719 26.461 26.931 28.443 25 .307 25.523 24. 085 24.000 22.860 22 .042 20.593 22.748 22.333 22.221 22.014 21.999 22.171 21.402 22.034 23.557 24 .011 23.843 24.529 19.930 19 .549 19 .103 19.448 17.687 1.00 17.38 1.00 19.10 1.00 15.32 1.00 15.59 1.00 13.47 1.00 14.40 1.00 10.86 1.00 21.22 1.00 22.35 1.00 22.92 1.00 22.08 1.00 25.16 1.00 23.49 1.00 26.03 1.00 27.91 1.00 30.97 1.00 27.10 1.00 0.00 1.00 22.55 1.00 21.40 1.00 19.96 1.00 14.21 1.00 12.69 1.00 26.54 1.00 29.17 1.00 30.58 1.00 0.00 1.00 32.23 1.00 41.61 1.00 49.21 1.00 58.98 1.00 61.43 1.00 63.31 1.00 32.90 1.00 32.88 1.00 32.93 1.00 0.00 1.00 35.42 312 ATOM 3270 CB ARG 1063 ATOM 327 CB RG 06337.598 -3.727 16.960 1.00 35.48

V

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15 ATOM

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25 ATOM

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3271 CG ARG 1063 3272 CD ARG 1063 3273 NE ARG 1063 3274 HE ARG 1063 3275 CZ ARG 1063 3276 NHl ARG 1063 3277 HH1l ARG 1063 3278 HH12 ARG 1063 3279 NH2 ARG 1063 3280 HH21 ARG 1063 3281 HH22 ARG 1063 3282 C ARG 1063 3283 0 ARG 1063 3284 N GLN 1064 3285 H GLN 1064 3286 CA GLN 1064 3287 CB GLN 1064 3288 CG GLN 1064 3289 CD GLN 1064 3290 OE1 GLN 1064 3291 NE2 GLN 1064 3292 HE21 GLN 1064 3293 HE22 GLN 1064 3294 C GLN 1064 3295 0 GLN 1064 3296 N LEU 1065 3297 H LEU 1065 3298 CA LEU 1065 3299 CB LEU 1065 3300 CG LEU 1065 3301 CD1 LEU 1065 3302 CD2 LEU 1065 3303 c LEIJ 1065 3304 o LEU 1065 3305 N ASN 1066 3306 H ASN 1066 3307 CA ASN 1066 3308 CS ASN 1066 37.655 37.188 37.008 37.719 35.907 34. 898 34.940 34.093 35.797 36.523 34.977 36.713 35.627 36.909 37.762 35.830 36.352 36.851 38.196 39.182 38.299 37 .505 39.155 35.088 35.558 33.918 33.595 33.198 31.724 30.663 29.344 30.997 33.898 33.752 34.778 34.903 35.648 36.216 -3 .611 -4 .928 -4.830 -5-.155 -4 .309 -3 .837 -3 .864 -3 .460 -4.302 -4.696 -3 .925 -1.428 -1.620 -0.313 -0.182 0.639 2 .068 2.699 2.187 2 .160 1.777 1.835 1.420 0.328 -0.469 0.946 1.616 0.759 1.156 0.137 0.884 -0 .502 1 .707 2.930 1.049 0.102 1.603 3 .006 15.450 14. 870 13.432 12.841 12.878 13.604 14.601 13.148 11. 555 10.991 11. 124 17.503 18.073 16.804 16.341 16.639 16.566 17.853 18.326 17.590 19 .573 20.148 19 .872 15 .353 14.524 15 .133 15.766 13 .881 13 .984 13.534 13 .414 12.182 12.925 12 .997 12 .172 12.392 11.142 11.467 1.00 37.92 1.00 38.55 1.00 44.21 1.00 0.00 1.00 44.14 1.00 46.11 1.00 0.00 1.00 0.00 1.00 44.51 1.00 0.00 1.00 0.00 1.00 38.94 1.00 38.58 1.00 43.24 1.00 0.00 1.00 46.48 1.00 45.17 1.00 50.93 1.00 51-83 1.00 56.19 1.00 51.87 1.00 0.00 1.00 0.00 1.00 51.07 1.00 52.23 1.00 55.53 1.00 0.00 1.00 57.02 1.00 61.19 1.00 64.64 1.00 67.26 1.00 66.64 1.00 56.04 1.00 55.83 1.00 54.44 1.00 0.00 1.00 54.22 1.00 55.90 313 ATOM 3309 CG ASN 1066 ATM 30 G SN106 36.994 3.104 12.771 1.00 56.20 ATOM 3310 OD1 ASN 1066 37.012 2.166 13.563 1.00 58.50 ATOM 3311 ND2 ASN 1066 37.655 4.203 13.086 1.00 56.65 ATOM 3312 HD21 ASN 1066 37.613 4.977 12.494 1.00 0.00 ATOM 3313 HD22 ASN 1066 38.176 4.166 13.918 1.00 0.00 ATOM 3314 C ASN 1066 36.849 0.671 11.002 1.00 53.31 ATOM 3315 0 ASN 1066 37.506 0.679 9.964 1.00 54.36 ATOM 3316 N GLY 1067 37.187 -0.137 12.010 1.00 50.83 ATOM 3317 H GLY 1067 36.761 -0.023 12.889 1.00 0.00 ATOM 3318 CA GLY 1067 38.314 -1.048 11.901 1.00 48.53 ATOM 3319 C GLY 1067 39.560 -0.517 12.601 1.00 47.35 S.eATOM 3320 0 GLY 1067 40.656 -1.066 12.421 1.00 49.79 ATOM 3321 N THR 1068 39.470 0.566 13.373 1.00 45.38 ATOM 3322 H- THR 1068 38.638 1.064 13.499 1.00 0.00 1 5 ATOM 3323 CA THR 1068 40.632 0.976 14.124 1.00 43.80 ATOM 3324 CB TER 1068 40.595 2.519 14.300 1.00 45.85 ATOM 3325 OGi THR 1068 39.344 2.942 14.840 1.00 47.48 ATOM 3326 HG1 THR 1068 39.235 2.533 15.712 1.00 0.00 ATOM 3327 CG2 THR 1068 40.883 3.172 12.947 1.00 40.16 ATOM 3328 c THR 1068 40.612 0.199 15.446 1.00 42.99 ATOM 3329 0 THR 1068 39.592 -0.421 15.800 1.00 43.98 ATOM 3330 N TYR. 1069 41.743 0.183 16.158 1.00 38.49 ATOM 3331 H TYR. 1069 42.458 0.791 15.905 1.00 0.00 .ATOM 3332 CA TYR 1069 41.953 -0.608 17.359 1.00 33.53 25 ATOM 3333 CB TYR 1069 42.953 -1.740 17.095 1.00 29.74 ATOM 3334 CG TYR 1069 42.345 -2.842 16.238 1.00 30.58 ATOM 3335 CD1 TYR 1069 42.488 -2.831 14.844 1.00 27.87 ATOM 3336 CE1 TYR 1069 41.922 -3.846 14.074 1.00 27.82 ATOM 3337 CD2 TYR 1069 41.636 -3.871 16.859 1.00 28.51 ATOM 3338 CE2 TYR 1069 41.071 -4.887 16.093 1.00 27.96 ATOM 3339 CZ TYR 1069 41.217 -4.864 14.711 1.00 27.78 ATOM 3340 OH TYR 1069 40.626 -5.861 13.973 1.00 33.15 ATOM 3341 HH TYR 1069 39.963 -6.295 14.520 1.00 0.00 ATOM 3342 C TYR 1069 42.520 0.307 18.415 1.00 33.52 ATOM 3343 0 TYR 1069 43.558 0.946 18.210 1.00 33.82 ATOM 3344 N ALA 1070 41.900 0.347 19.580 1.00 32.06 ATOM 3345 H ALA 1070 41.151 -0.261 19.769 1.00 0.00 ATOM 3346 CA ALA 1070 42.324 1.263 20.603 1.00 28.04 ATOM 3347 CB ALA 1070 41.605 2.580 20.437 1.00 26.29 314 ATOM 3348 C ALA 1070 S

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3349 0 ALA 1070 3350 N ILE 1071 3351 H ILE 1071 3352 CA ILE 1071 3353 CB ILE 1071 3354 CG2 ILE 1071 3355 CG1 ILE 1071 3356 CD ILE 1071 3357 C ILE 1071 3358 o ILE 1071 3359 N ALA 1072 3360 H ALA 1072 3361 CA ALA 1072 3362 CB ALA 1072 3363 C ALA 1372 3364 o ALA 1072 3365 N GLY 1073 3366 H GLY 1073 3367 CA GLY 1073 3368 c GLY 1073 3369 0 GLY 1073 3370 N GLY 1074 3371 H GLY 1074 3372 CA GLY 1074 3373 c GLY 1074 33-74 0 GUI 1074 3375 N LYS 1075 3376 H LYS 10 75 3377 CA LYS 1075 3378 CB LYS 1075 3379 CG LYS 1075 3380 CD LYS 1075 3381 CE LYS 1075 3382 NZ LYS 1075 3383 HZ1 LYS 1075 3384 HZ2 LYS 1075 3385 HZ3 LYS 1075 3386 c LYS 1075 45.003 46.364 41.806 42.087 40.711 40.567 39.775 38.653 40.407 41.009 40.290 39.880 40.820 42.222 42.806 42 .812 42.335 44 .139 44.037 42.964 45.187 45.948 45.300 46.760 47.012 48.403 48.647 47.819 46.818 47.969 48.087 44.719 41.992 0.722 21.976 1.00 27.69 40.919 0.153 22.184 1.00 29.45 42.935 0.860 22.905 1.00 26.64 43.779 1.277 22.641 1.00 0.00 42.709 0.579 24.313 1.00 27.04 44.032 0.635 25.117 1.00 25.62 43.730 0.441 26.608 1.00 25.21 -0.438 24.603 1.00 26.34 -0.464 25.318 1.00 23.97 1.739 24.694 1.00 31.25 2.874 24.292 1.00 35.46 1.527 25.413 1.00 38.50 0.631 25.776 1.00 0.00 2.603 25.750 1.00 43.90 2.053 26.636 1.00 44.68 3 .805 26.464 1.00 45.61 3.680 27.536 1.00 45.17 4.959 25.796 1.00 46.20 4.931 24.912 1.00 0.00 6.231 26.267 1.00 44.42 6.531 25.730 1.00 43.18 7.578 26.027, 1.00 46.40 5.634 24.947 1.00 39.43 4.822 24.678 1.00 0.00 5.851 24.424 1. 00 34.46 6 .104 22.947 1-00 34.61 6.354 22.378 1.00 36.50 5.951 22.314 1.00 37.26 5.572 22.802 1.00 0.00 6.215 20.896 1.00 39.16 6.409 20.566 1.00 42.86 7.475 19.510 1.00 45.51 8.077 19.775 1.00 51.14 8.663 21.198 1.00 48.74 9.817 21.511 1.00 46.00 9 .539 21.522 1.00 0.00 10.554 20.793 1.00 0.00 10.187 22.444 1.00 0.00 5.125 20.005 1.00 40.24 315

C

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3387 3388 3389 3390 3391 3392 3393 3394 3395 3396 3397 3398 3399 3400 3401 3402 3403 3404 3405 3406 3407 3408 3409 3410 3411 3412 3413 3414 3415 3416 3417 3418 3419 3420 3421 3422 3423 3424 3425 O LYS 1075 N ALA 1076 H ALA 1076 CA ALA 1076 CB ALA 1076 C ALA 1076 O ALA 1076 N HIS 1077 H HIS 1077 CA HIS 1077 CB HIS 1077 CG HIS 1077 CD2 HIS 1077 ND1 HIS 1077 HD1 HIS 1077 C-71 HIS 1077 NE2 HIS 1077 H--2 HIS 1077 C HIS 1077 O HIS 1077 N CYS 1078 H CYS 1078 CA CYS 1078 CS CYS 1078 SC CYS 1078 C CYS 1078 o CYS 1078 N GLY 1079 H GLY 1079 CA CLY 1079 C GLY 1079 O CLY 1079 N PRO 1080 CD PRO 1080 CA PRO 1080 C3 PRO 1080 CG PRO 1080 C PRO 1080 c PRO 1080 44.968 43.983 43.867 43.411 42.390 44.577 45.597 44. 485 43.653 45.516 46.386 47.188 48.402 46.898 46.011 47.889 48.786 49.577 44.771 43 .544 45.467 46.439 44.853 45.069 44.397 45.693 46.927 45.083 44.104 45.849 46.508 47.123 46.431 45.738 47.049 46.520 46.349 48.559 49.245 3 .916 5 .616 6.585 4 .772 5 .517 4 .383 5 .070 2.682 2 .622 1 .682 2.367 2 .946 2 .502 2 .402 3 .129 3.391 3 .946 1. 821 1. 699 1.272 1.382 0.414 0.998 2 .671 -0.832 -0 .752 -1.969 -1.984 -3 .185 -3 .249 -2.286 -4.401 -5 .599 -4 .627 -5.965 -6.680 -4.583 -4 .177 20.185 19.003 18.930 17.969 17.112 17.084 16.985 16.2 16.622 15.693 16.493 17.574 17.353 18.866 19.292 19.438 18 .517 18.657 14.644 14.698 13 .664 13.603 12.666 11.256 11.011 12 .890 12.852 13 .190 13.206 13.436 14.823 15.309 15.503 15.044 16.812 17 .245 15.921 16.707 17.651 1.00 37.79 1.00 40.40 1.00 0.00 1.00 39.60 1.00 40.11 1.00 38.92 1.00 40.33 1.00 0.00 1.00 41.38 1.00 38.84 1.00 37.80 1.00 37.54 1.00 41.89 1.00 0.00 1.00 40.69 1.00 42.21 1.00 0.00 1.00 44.66 1.00 43.75 1.00 49.78 1.00 0.00 1.00 54.24 1.00 58.19 1.00 71.36 1.00 51.82 1.00 55.71 1.00 47.69 1.00 0.00 1.00 43.67 1.00 40.20 1.00 40.36 1.00 37.25 1.00 36.81 1.00 34.51 1.00 35.28 1.00 37.15 1.00 31.54 1.00 31.30 -316

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3426 3427 3428 3429 3430 3431 3432 3433 3434 3435 3436 3437 3438 3439 3440 3441 3442 3443 3444 3445 3446 3447 3448 3449 3450 3451 3452 3453 3454 3455 3456 3457 3458 3459 3460 3461 3462 3463

N

H

CA

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0

N

H

CA

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ALA 1081 ALA 1081 ALA 1081 ALA 1081 ALA 1081 ALA 1081 GLtJ 1082 GLU 1082 GLU 1082 GLU 1082 CLU 1082 GLU 1082 GLU 1082 GLU 1082 CLU 1082 GLU 1082 LEU 1083 LEU 1083 LEU 1083 LEU 1083 LEU 1083 LEU 1083 LEU 1083 LEU 1083 LEU 1083 CYS 1084 CYS 1084 CYS 1084 CYS 1084 CYS 1084 CYS 1084 CYS 1084 GLU 1085 GLU 1085 GLU 1085 CLU 1085 GLU 1085 GLU 1085 49.084 -4.958 48.480 -5.268 50.515 -4.940 50.778 -5.435 51.109 -3.545 52.098 -3.360 50.462 -2.534 49.612 -2.707 50.923 -1.146 50.117 -0.257 50.445 -0.415 50.414 -1.848 49.335 -2.445 51.485 -2.364 50.755 -0.649 51.671 -0.026 49.605 -0.991 48.939 -1.519 49.329 -0.592 48.008 -1.212 47.531 -0.830 46.038 -0.643 47.943 -1.898 50.466 -0.996 50.966 -0.135 50.930 -2.252 50.514 -2.867 51.988 -2.721 52.242 -4.221 50.901 -5.192 53.283 -2.018 53.989 -1.702 53.588 -1.719 52.937 -1.899 54.856 -1.083 55.035 -0.981 56.513 -1.026 56.801 -0.768 57.850 -0.176 15.528 14.829 15.256 13.827 15.416 16.136 14. 822 14.365 14.906 13.961 12.480 11.968 11. 933 11.638 16.328 16.874 16 .942 16.448 18.309 18.799 20.215 20.202 21.226 19.227 19 .966 19 .124 18.482 20.002 19.865 20.592 19.722 20.679 18.447 17.737 18.105 16.595 16.217 14.736 14.444 1.00 30.26 1.00 0.00 1.00 30.04 1.00 29.58 1.00 30.25 1.00 31.27 1.00 32.52 1.00 0.00 1.00 31.86 1.00 33.49 1.00 34.68 1.00 38.35 1.00 38.71 1.00 41.55 1.00 29.07 1.00 28.55 1.00 27.23 1.00 0.00 1.00 26.74 1.00 25.43 1.00 21.57 1.00 20.84 1.00 19.23 1.00 29.37 1.00 31.06 1.00 32 .62 1.00 0.00 1.00 31.81 1.00 31.52 1.00 29.87 1.00 31.85 1.00 31.54 1.00 33.95 1.00 0.00 1.00 35.05 1.00 40.13 1.00 49.97 1.00 60.29 1.00 68.30 ATOM 3464 QEl GLU 1085 317 ATOM 3465 OE2 GLU 1085 ATOM 3465 0E2GLU 08555.991 -1.138 13.874 1.00 62.08 a)

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1 5 ATOM

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20 ATOM

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3466 3467 3468 3469 3470 3471 3472 3473 3474 3475 3476 3477 3478 3479 3480 3481 3482 3483 3484 3485 3486 3487 3488 3489 3490 3491 3492 3493 3494 3495 3496 3497 3498 3499 3500 3501 3502 3503 C GLU O GLU N PHE H PHE CA PHE CB PHE CG PHE CD1 PHE CD2 PHE CEl PHE CE2 PHE CZ PHE C PHE O PHE N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CEl TYR CD2 TYR CE2 TYR 1085 1085 1086 1086 1086 1086 1086 1086 1086 1086 1086 1086 1086 1086 1087 1087 1087 1087 1087 1087 1087 1087 1087 1087 1087 1087 1087 1087 1088 1088 1088 1088 1088 1088 1088 1088 1089 1089 54.869 55.861 53.721 52.970 53.545 52.090 51. 772 52.277 51. 030 52.045 50.798 51. 308 53 .901 54.661 53.396 52.828 53 .662 52.527 51. 192 50.221 49 .005 50.924 49.703 48.746 47.531 47.453 55.036 55.537 55.716 55.266 57.099 57.538 56.747 57.236 57.985 59.047 57.570 56.773 0.306 0.678 1. 005 0.583 2.341 2 .777 4.100 5.298 4.112 6.494 5.308 6.495 2.373 3.239 1.415 0.726 1.372 0.572 1.346 1.141 1.835 2.266 2.963 2.744 3.426 3.794 0.814 0.983 0.129 -0.198 -0.270 150 -2.337 -3 .023 0.978 0.995 2. 047 1.973 18.701 19.333 18.599 18.135 19.136 18.895 19.578 19.057 20.770 19.739 21.451 20.934 20.627 21.084 21.399 20.994 22.824 23.476 23.507 22.520 22.550 24.538 24 .572 23 .580 23 .619 24.512 23 .165 24.290 22.241 21.430 22.439 21.271 21.159 21.637 22.531 23.183 21.843 21.274 1.00 32.52 1.00 33.29 1.00 31.71 1.00 0.00 1.00 31.07 1.00 29.64 1.00 34.51 1.00 38.20 1.00 37.01 1.00 37.34 1.00 33.21 1.00 39.15 1.00 32.70 1.00 36.52 1.00 32.45 1.00 0.00 1.00 28.99 1.00 29.23 1.00 28.38 1.00 28.31 1.00 26.26 1.00 29.02 1.00 24.57 1.00 26.40 1.00 26.78 1.00 0.00 1.00 30.34 1.00 30.02 1.00 33.87 1.00 0.00 1.00 37.71 1.00 40.54 1.00 40.91 1.00 0.00 1.00 41.25 1.00 38.81 1.00 44.94 1.00 0.00 318 ATOM 3504 CA ARG 1089 58.272 3.314 21.934 1.00 48.42 ATOM 3505 CB ARG 1089 58.161 4.166 20.656 1.00 49.53 ATOM 3506 CC ARG 1089 58.895 3.689 19.410 1.00 47.71 ATOM 3507 CD ARG 1089 58.041 2.725 18.614 1.00 48.46 ATOM 3508 NE ARG 1089 56.856 3.372 18.072 1.00 51.23 ATOM 3509 HE ARG 1089 56.280 3.894 18.668 1.00 0.00 ATOM 3510 CZ ARC 1089 56.517 3.268 16.778 1.00 54.05 ATOM 3511 NH1 ARG 1089 57.265 2.560 15.912 1.00 52.77 ATOM 3512 HH11 ARG 1089 58.098 2.101 16.219 1.00 0.00 ATOM 3513 HH12 ARG 1089 56.995 2.514 14.951 1.00 0.00 ATOM 3514 NH2 ARG 1089 55.391 3.865 16.355 1.00 50.10 ATOM 3515 HH2 1 ARG 1089 54.825 4.373 17.002 1.00 0.00 *ATOM 3516 HH2 2 ARG 1089 55.130 3.814 15.391 1.00 0.00 ATOM 3517 C ARG 1089 57.655 4.107 23.072 1.00 48.92 15 ATOM 3518 0 ARG 1089 58.270 4.220 24.138 1.00 49.60 :**ATOM 3519 N ASP 1090 56.422 4.580 22.877 1.00 50.51 ATOM 3520 H ASP 1090 55.905 4.297 22.092 1.00 0.00 ATOM 3521 CA ASP 1090 55.753 5.447 23.834 1.00 55.15 ATOM 3522 CB ASP 1090 55.177 6.659 23.071 1.00 56.05 20 ATOM 3523 CC ASP 1090 54.281 7.584 23.889 1.00 55.59 ATOM 3524 ODi ASP 1090 53.104 7.678 23.550 1.00 57.02 ATOM 3525 0D2 ASP 1090 54.748 8.189 24.854 1.00 57.74 ATOM 3526 c ASP 1090 54.653 4.774 24.659 1.00 55.94 ATOM 3527 o ASP 1090 53.592 4.432 24.115 1.00 55.42 ATOM 3528 N PRO 1091 54.835 4.624 25.984 1.00 55.78 ATOM 3529 CD PRO 1091 56.135 4.706 26.655 1 .00 55.19 ATOM 3530 CA PRO 1091 53.801 4.154 26.897 1.00 55.95 ATOM 3531 CB PRO 1091 54.598 3.706 28.114 1.00 56.04 ATOM 3532 CC PRO 1091 55.792 4.624 28.138 1.00 55.88 ATOM 3533 c PRO 1091 52.688 5.146 27.220 1.00 56.97 ATOM 3534 0 PRO 1091 52.486 5.489 28.389 1.00 57.39 ATOM 3535 N ASP 1092 51.933 5.654 26.238 1.00 58.63 ATOM 3536 H ASP 1092 52.090 5.339 25.318 1.00 0.00 ATOM 3537 CA ASP 1092 50.820 6.556 26.519 1.00 58.70 ATOM 3538 CB ASP 1092 50.155 7.027 2S.210 1.00 63 .88 ATOM 3539 CC ASP 1092 48.815 7.764 25.350 1.00 70.81 ATOM 3540 OD1 ASP 1092 47.831 7.289 24.774 1.00 74.91 ATOM 3541 0D2 ASP 1092 48.747 8.794 26.029 1.00 70.73 ATOM 3542 C ASP 1092 49.792 5.826 27.385 1.00 57.19 319 a. 15 20 ATOM 3543 0 ASP 1092 ATOM 3544 N GLY 1093 ATOM 3545 H GLY 1093 ATOM 3546 CA GLY 1093 ATOM 3547 C GLY 1093 ATOM 3548 0 GLY 1093 ATOM 3549 N LEU 1094 ATOM 3550 H LEU 1094 ATOM 3551 CA LEU 1094 ATOM 3552 CB LEU 1094 ATOM 3553 CG LEU 1094 ATOM 3554 CD1 LEU 1094 ATOM 3555 CD2 LEU 1094 ATOM 3556 C LEU 1094 ATOM 3557 0 LEU 1094 ATOM 3558 N PRO 1095 ATOM 3559 CD PRO 1095 ATOM 3560 CA PRO 1095 ATOM 3561 CB PRO 1095 ATOM 3562 CC PRO 1095 ATOM 3563 c PRO 1095 ATOM 3564 0 PRO 1095 ATOM 3565 N CYS 1096 ATOM 3566 H CYS 1096 ATOM 3567 CA CYS 1096 ATOM 3568 CS CYS 1096 ATOM 3569 SC CYS 1096 ATOM 3570 c CYS 1096 ATOM 3571 0 CYS 1096 ATOM 3572 N ASN 1097 ATOM 3573 H ASN 1097 ATOM 3574 CA ASN 1097 ATOM 3575 C3 ASN 1097 ATOM 3576 CC ASN 1097 ATOM 3577 ODi ASN 1097 ATOM 3578 ND2 ASN 1097 ATOM 3579 HD21 ASN 1097 ATOM 3580 HD22 ASN 1097 ATOM 3581 C ASN 1097 49.932 50.717 49-.040 49.403 48.533 50.665 51.386 50.984 51.649 50.921 49.570 51.824 51.880 52 .543 51.866 50.737 52.888 52.491 50.991 54.342 55.202 54.666 53 .997 55.982 57.041 56.640 55.800 54.686 56.824 57.719 56.696 57.775 59.179 59.559 59.996 59.662 60.893 56.843 6.112 28.666 1.00 55.12 6.617 28.959 1.00 0.00 5.583 29.665 1.00 53.01 4.161 30.026 1.00 48.92 3.358 30.361 1.00 52.72 3.777 29.993 1.00 45.02 4.424 29.840 1.00 u.00 2.413 30.331 1.00 40.34 1.749 29.132 1.00 38.94 0.611 28.409 1.00 36.60 1.068 27.871 1.00 31.39 0.120 27.283 1.00 37.39 2.366 31.555 1.00 39.95 3.351 31.881 1.00 39.55 1.249 32.290 1.00 40.07 0.328 32.367 1.00 42.05 0.848 33.241 1.00 41.65 -0.578 33.571 1.00 41.38 -0.476 33.630 1.00 41.02 0.990 32.799 1.00 42.06 1.307 33.630 1.00 45.34 0.605 31.565 1.00 40.67 0.185 30.981 1.00 0.00 0.797 30.961 1.00 38.40 -0.184 31.463 1.00 39.77 -1.942 31.408 1.00 39.49 0.558 29.486 1.00 37.14 0.204 29.075 1.00 36.74 0.800 28.670 1.00 37.32 0.997 29.013 1.00 0.00 0.535 27.245 1.00 36.40 1.260 26.443 1.00 33.25 0.822 26.788 1.00 32.16 0.769 27.957 1.00 34.46 0.486 25.810 1.00 35.25 0.517 24.892 1.00 0.00 0.203 26.064 1.00 0.00 -0.968 27.051 1.00 38.24 48.978 5.011 26.942 1.00 56.76 a a a -320

S

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

3582 3583 3584 3585 3586 3587 3588 3589 3590 3591 3592 3593 3594 3595 3596 3597 3598 3599 3600 3601 3602 36031 3604 3605 36061 3607 3608 3609 3610 3611 3612 3613 3614 3615 3616 3617 3618 3619 3620 0 ASN 1097 N LEU 1098 H LEU 1098 CA LEU 1098 CB LEU 1098 CG LEU 1098 CD1 LEU 1098 CD2 LEU 1098 C LEU 1098 0 LEU 1098 N ARG 1099 H ARG 1099 CA ARG 1099 CB ARG 1099 CG ARC 1099 CD ARG 1099 NE ARG 1099 HE ARC 1099 CZ ARG 1099 NH1 ARC 1099 iHl1 ARC 1099 iH12 ARC 1099 NH2 ARG 1099 iH21 ARC 1099 iH22 ARG 1099 C ARC 1099 0 ARG 1099 N LYS 1100 H LYS 1100 CA LYS 1100 CB LYS 1100 CG LYS 1100 CD LYS 1100 CE LYS 1100 NZ LYS 1100 HZ1 LYS 1100 HZ2 LYS 1100 HZ3 LYS 1100 C LYS 1100 57.278 -1.726 56.431 -1.443 56.119 -0.821 56.504 -2.861 55.537 -3.194 54.094 -2.729 53.306 -3.185 53.496 -3.273 57.941 -3.103 58.515 -2.385 58.565 -4.056 58.053 -4.563 59.951 -4.369 60.768 -4.250 60.776 -2.845 61.588 -2.775 61.307 -1.550 60.933 -0.777 61.545 -1.435 62.068 -2.432 62.294 -3.306 62.221 -2.304 61.216 -0.312 60.796 0.443 61.379 -0.226 60.063 -5.778 60.240 -5.942 59.891 -6.841 59.427 -6.750 60.158 -8.157 60.795 -9.008 61.296 -10.344 61.978 -11.153 62.305 -12.569 61.103 -13.374 60.468 -12.912 60.623 -13.472 61.370 -14.316 58.848 -8.765 27.938 25.886 25.196 25.619 24.494 24.669 23.475 25.960 25.237 24.418 25.901 26.551 25.656 26.964 27.586 28.889 29.650 29.176 30.972 31.691 31.262 32.670 31.612 31.108 32.594 25 .093 23.881 25.868 26.727 25.324 26.411 25.868 26.969 26.488 26.322 25.642 27.240 25.969 24.833 1.00 40.46 1.00 35.38 1.00 0.00 1.00 30.02 1.00 29.07 1.00 26.84 1.00 27.25 1.00 31.57 1.00 29.99 1.00 30.27 1.00 32.01 1.00 0.00 1.00 33.13 1.00 33.84 1.00 37.15 1.00 42.03 1.00 45.59 1.00 0.00 1.00 44.75 1.00 47.19 1.00 0.00 1.00 0.00 1.00 41.73 1.00 0.00 1.00 0.00 1.00 35.07 1.00 35.29 1.00 34.71 1.00 0.00 1.00 37.09 1.00 42.93 1.00 53 .06 1.00 57.15 1.00 61.71 1.00 65.62 1.00 0.00 1.00 0.00 1.00 0.00 1.00 37.79 321 ATOM 3621 o LYS 1100 ATM 62 0 LY 100 57.914 -8.899 25.637 1.00 39.77

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

3622 3623 3624 3625 3626 3627 3628 3629 3630 3631 3632 3633 3634 3635 3636 3637 3638 3639 3640 3641 3642 3643 36441 3645 3646 3647 3648 3649 3650 3651 3652 3653 3654 3655 3656 36571 3658 3659

N

CD

CA

CB

CG

C

0

N

H

CA

CB

SG

C

0

N

H

CA

CB

CG

OD1 ND2 HD2 1 HD2 2

C

0

PRO

PRO

PRO

PRO

PRO

PRO

PRO

CYS

CYS

CYS

CYS

CYS

CYS

CYS

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ARG

ARG

ARG

ARG

ARG

ARG

1101 1101 1101 1101 1101 1101 1101 1102 1102 1102 1102 1102 1102 1102 1103 1103 1103 1103 1103 1103 1103 1103 1103 1103 1103 1104 1104 1104 1104 1104 1104 1104 1104 1104 1104 1104 1104 1104 58.672 -9.097 59.557 -8.728 57.514 -9.832 57.701 -9.840 58.594 -8.657 57.539 -11.213 58.573 -11.890 56.480 -11.707 55.634 -11.216 56.534 -13.050 55.525 -13.239 55.550 -14.875 56.120 -13.868 54.939 -14.057 57.153 -14.223 58.060 -13.985 56.945 -i4.999 58.160 -14.805 58.030 -13.536 58.871 -13.209 57.000 -12.709 56.232 -12.920 57.117 -11.875 56.668 -16.460 57.148 -17.042 55.745 -16.955 55.445 -16.404 55.177 -18.280 54.266 -18.536 52.888 -18.950 51.989 -19.095 51.863 -17.832 51.489 -17.084 52.257 -17.629 52.803 -18.572 52.937 -19.496 53.075 -18.349 52.098 -16.401 23.543 22.448 23.050 21. 556 21.285 23.683 23 .614 24.317 24.333 24.891 26.041 26.838 23.679 23.356 22.921 23.213 21.730 20.822 19 .974 19 .144 20.053 20. 617 19 .552 22.044 23.027 21.217 20.468 21.333 20 .161 20.569 19.367 18.700 19.203 17.447 16.669 17 .023 15 .734 1.00 34.56 1.00 32.70 1.00 33.16 1.00 34.82 1.00 34.87 1.00 30.83 1.00 33.53 1.00 29.51 1.00 0.00 1.00 27.74 1.00 24.93 1.00 25.54 1.00 28.20 1.00 24.55 1.00 25.01 1.00 0.00 1.00 27.34 1.00 25.34 1.00 24.69 1.00 31.34 1.00 27.90 1.00 0.00 1.00 0.00 1.00 27.74 1.00 27.94 1.00 26.87 1.00 0.00 1.00 26.33 1.00 24.23 1.00 25.72 1.00 24.23 1.00 24.12 1.00 0.00 1.00 24.35 1.00 22.87 1.00 0.00 1.00 0.00 NE ARG HE ARG CZ ARO NH1 ARO iH11 ARO iHl2 ARG NH2 ARG 16.999 1.00 26.96 322

C.

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

3662 3663 3664 3665 3666 3667 3668 3669 3670 3671 3672 3673 3674 3675 3676 3677 3678 3679 3680 3681 3682 3683 3684 3685 3686 3687 3688 3689 3690 3691 3692 3693 3694 3695 3696 3697 3698 C ARG 1104 O ARG 1104 N PRO 1105 CD PRO 1105 CA PRO 1105 CB PRO 110 5 CG PRO 1105 C PRO 1105 0 PRO 1105 N SER 1106 H SER 1106 CA SER 1106 CB SER 1106 OG SER 1106 HG SER 1106 C SER 1106 O SER 1106 N GLY 1107 H GLY 1107 CA GLY 1107 C GLY 1107 O GLY 1107 N L EU 110 8 H L E' 1:08 CA LE'- 1108 CB LE'- 1108 CG LET' ,108 CD1 LEU 1108 CD2 LETU 1108 C LEU 1108 O L EU 1108 N GLU 1109 H GLU 1109 CA GLtJ 1109 CB GLU 1109 CG GLU 1109 CD GLIC 1109 3660 HH21 ARG 1104 3661 HH22 ARG 1104 51.687 -15.710 52.368 -16.154 56.248 -19.341 57.056 -19.403 56.321 -20.176 55.548 -20.058 57.209 -21.331 56.899 -21.986 55.515 -21.495 56.960 -22.209 55.865 -22.738 57.945 -22.269 58.734 -21.704 57.886 -23.014 59.331 -23.177 59.964 -21.896 60.814 -21.945 57.161 -24.356 57.443 -25.230 56.127 -24.464 55.849 -23.683 55.285 -25.640 53.901 -25.219 52.903 -25.817 53.845 -24.188 54.668 -23.763 52.603 -23.628 52.839 -22.863 51.627 -22.255 50.821 -23.356 52.036 -21.299 52.108 -22.688 52.868 -21.897 50.829 -22.822 50.292 -23.421 50.141 -22.052 49.349 -22.970 50.244 -23.684 50.907 -22.718 17.595 16.074 21.367 20.438 22.403 23.635 22.426 23.770 24.134 21.197 21.004 20.306 20.434 19 .058 18.574 18.565 18.119 19.157 19 .979 18.336 17.814 18. 361 18 .826 18.411 19 .667 19 .977 2 0:.13 3 21.434 22 .107 22.737 23 .185 19 .037 18.471 18.731 19.287 17.715 16.765 15.754 14.771 1.00 0.00 1.00 0.00 1.00 25.95 1.00 25.69 1.00 26.74 1.00 29.26 1.00 32.94 1.00 28.93 1.00 30.42 1.00 38.12 1.00 38.58 1.00 43.86 1.00 0.00 1.00 49.42 1.00 51.93 1.00 55.67 1.00 0.00 1.00 49.17 1.00 51.15 1.00 47.64 1.00 0.00 1.00 43.01 1.00 39.30 1.00 42.80 1 .00 30.41 1.00 0.00 1.00 24.96 1.00 25.86 1.00 26.69 1.00 30.10 1.00 29.77 1.00 19.07 1.00 19.17 1.00 11.01 1.00 0.00 1.00 13 .68 1.00 15.71 1.00 3 .36 1.00 14.34 C. C 323 .5 5.*

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

3699 OE1 GLU 1109 3700 0E2 GLU 1109 3701 C GLU 1109 3702 0 GLU 1109 3703 N PRO 1110 3704 CD PRO 1110 3705 CA PRO 1110 3706 CB PRO 1110 3707 CG PRO 1110 3708 c PRO 1110 3709 0 PRO 1110 3710 N GLN 1111 3711 H GLN 1111 3712 CA GLN 1111 3713 GB GLN 1111 3714 CG GLN 1111 3715 CD GLN 1111 3716 OE1 GLN 1111 3717 NE2 GLN 1111 3718 HE21 GLN 1111 3719 HE22 GLN 1111 3720 c GLN 1111 3721 o GLN 1111 3722 N PRO 1112 3723 CD PRO 1112 3724 Cl PRO 1112 3725 GB PRO 1112 3726 CG PRO 1112 3727 c PRO 1112 3728 o PRO 1112 3729 N GLY 1113 3730 H GLY 1113 3731 CA GLY 1113 3732 C GLY 1113 3733 0 GLY 1113 3734 N VAL 1114 3735 H VAL 1114 3736 CA VAL 1114 3737 CB VAL 1114 52.127 -22.779 50.226 -21.925 49.168 -21.137 48.936 -21.367 48.573 -20.099 49.101 -19.362 47.375 -19.456 47.003 -18.460 48.342 -18.025 46.311 -20.503 46.240 -21.529 45.539 -20.283 45.659 -19.457 44.477 -21.190 44.351 -21.103 43.385 -22.049 43.676 -23.532 42.757 -24.348 44.929 -23.965 45.691 -23.340 45.064 -24.928 43.206 -20.728 42.856 -19.555 42.514 -21.525 42.844 -22.911 41.305 -21.123 40.998 -22.286 41.526 -23.474 40.213 -20.825 40.200 -21.368 39.267 -19.977 39.267 -19.606 38.234 -19.632 37.089 -20.616 36.646 -21.008 36.534 -20.984 37.000 -20.757 35.340 -21.823 34.907 -22.210 14.666 14. 101 18.425 19.623 17.794 16.640 18.309 17.242 16.680 18.583 17.895 19.648 20.161 20.058 21. 584 22.286 22.089 21. 959 22.030 22.074 21. 948 19.348 19.522 18.509 18.181 17.811 16.909 17.670 18.815 19.930 18.447 17.544 19.391 19.363 18.289 20.510 21.341 20.532 21.964 1.00 14.12 1.00 18.46 1.00 15.87 1.00 17.90 1.00 12.87 1.00 9.54 1.00 10.18 1.00 11.89 1.00 12.40 1.00 13.76 1.00 18.10 1.00 14.71 1.00 0.00 1.00 17.01 1.00 18 .38 1.00 23.45 1.00 28.59 1.00 29.01 1.00 27.57 1.00 0.00 1.00 0.00 1.00 20.44 1.00 21.59 1.00 23.22 1.00 23.13 1.00 20.52 1.00 22.54 1.00 23 .92 1.00 24.15 1.00 30.52 1.00 23.10 1.00 0.00 1.00 19.43 1.00 16.65 1.00 18 .76 1.00 13.19 1.00 0.00 1.00 14.63 1.00 15.86 324 ATOM 3738 CG1 VAL 1114 33.601 -22.9982.90 101.0 21.950 1.00 12.00

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

3739 3740 3741 3742 3743 3744 3745 3746 3747 3748 3749 3750 3751 3752 3753 3754 3755 3756 3757 3758 3759 3760 3761 3762 3763 3764 3765 3766 3767 3768 3769 3770 3771 3772 3773 3774 3775 3776

PHE

PHE

PE

PE

PE

a CG2 VAL C VAL 0 VAL CD1 PE CD2 PE CEl PE CE2 PE CZ PHE C PE O PHE N ASP H ASP CA ASP CB ASP CG ASP ODi ASP OD2 ASP C ASP O ASP N CYS H CYS CA CYS CB CYS SG CYS C CYS O CYS N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU 1114 1114 1114 1115 1115 1115 1115 1115 1115 1115 1115 1115 1115 1115 1115 1116 1116 1116 1116 1116 1116 1116 1116 1116 1117 1117 1117 1117 1117 1117 1117 1118 1118 1118 1118 1118 1118 1118 35 .981 -23 .080 34.182 -21.083 33.443 -21.670 33.998 -19.804 34.572 -19.392 32.902 -19.029 32.909 -17.600 31.577 -16.871 30.397 -17.551 31.537 -15.490 29.199 -16.865 30.328 -14.805 29.161 -15.488 33.025 -18.962 32.066 -19.184 34.234 -18.697 34.964 -18.588 34.524 -18.601 36.045 -18.374 36.719 -17.147 37.891 -16.890 36.110 -16.449 34.076 -19.895 33.320 -19.831 34.413 -21.061 34.979 -21.075 34.034 -22.350 34.723 -23.478 36.536 -23.316 32.531 -22.513 31.923 -23.045 31.881 -21.997 32.402 -21.553 30.431 -22.098 29.978 -21.517 28.763 -22.045 28.307 -20.886 27.544 -22.433 22.586 19.903 19.117 20.235 20.907 19.669 20. 244 20. 131 19.840 20.321 19.742 20.222 19.934 18 .146 17.415 17.657 18.291 16.242 16.039 16.693 16.396 17.506 15 .576 14.610 16.139 16.939 15 .572 16.348 16.425 15.634 14.701 16.680 17 .381 16.849 18.192 18 .959 19.786 18.126 1.00 18.74 1.00 13.31 1.00 17.48 1.00 11.59 1.00 0.00 1.00 14.67 1.00 10.62 1.00 9.10 1.00 7.14 1.00 11.41 1.00 9.87 1.00 9.09 1.00 7.44 1.00 17.73 1.00 16.85 1.00 18.54 1.00 0.00 1.00 21.41 1.00 26.96 1.00 29.54 1.00 32.73 1.00 33.86 1.00 18.86 1.00 20.05 1.00 18.63 1.00 0.00 1.00 17.24 1.00 18.30 1.00 26.14 1.00 14.66 1.00 21.58 1.00 16.74 1.00 0.00 1.00 14.92 1.00 15.40 1.00 19.35 1.00 20.69 1.00 19.69 325 ATOM 3777 C LEU 1118 29.739 -21.314 1.75 .0 134 15.755 1.00 13.42

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

3778 3779 3780 3781 3782 3783 3784 3785 3786 3787 3788 3789 3790 3791 3792 3793 3794 3795 3796 3797 3798 3799 3800 3801 3802 3803 3804 3805 3806 3807 3808 3809 3810 3811 3812 3813 3814 3815 O LEU 1118 N ARG 1119 H ARG 1119 CA ARG 1119 CB ARG 1119 CG ARG 1119 CD ARG 11190 NE ARG 1119 HE ARG 1119 CZ ARG 1119 NH1 ARG 1119 HH11 ARG 1119 EH12 ARG 1119 NH2 ARG 1119 HiH21 ARG 1119 ~iH22 ARG 1119 C ARG 1119 O ARG 1119 N ASP 1120 H ASP 1120 CA ASP 1120 CB ASP 1120 CG ASP 1120 ODi ASP 1120 0D2 ASP 1120 C ASP 1120 o ASP 1120 N ALA 1121 H ALA 1121 CA ALA 1121 CB ALA 1121 C ALA 1121 o ALA 1121 N MET 1122 H MET 1122 CA MET 1122 CB MET 1122 CG MET 1122 28.874 -21.856 30.103 -20.049 30.822 -19.690 29.506 -19.188 30.169 -17.814 29.866 -16.868 in rrn -Ic 31.494 -15.252 31.083 -15.218 32.793 -14.973 33.472 -14.963 33.013 -15.183 34.449 -14.751 33.442 -14.720 32.949 -14.741 34.418 -14.503 29.674 -19.828 28.718 -19.836 30.848 -20.406 31.568 -20.357 31.101 -21.113 32.511 -21.706 33.616 -20.731 33.434 -19.945 34.670 -20.772 30.113 -22.243 29.540 -22.365 29.888 -23.054 30.393 -22.917 28.937 -24.140 28.945 -24.943 27.545 -23.577 26.809 -24.130 27.156 -22.459 27.767 -22.050 25.854 -21.832 25.613 -20.720 25.432 -21.261 15. 066 15.560 16. 116 14.549 14.511 15.654 16.483 17.373 16.400 15.257 14.396 15.265 17.532 18.402 17.515 13.182 12.404 12.885 13.552 11.627 11.604 11. 243 10.315 11.878 11. 386 10.290 12.430 13.262 12.339 13 .637 12. 085 11.262 12.713 13.365 12.467 13 .492 14.904 1.00 17.93 1.00 18.04 1.00 0.00 1.00 20.03 1.00 23.89 1.00 23.86 1.00 27.03 1.00 0.00 1.00 27.13 1.00 28.80 1.00 0.00 1.00 0.00 1.00 36.40 1.00 0.00 1.00 0.00 1.00 20.52 1.00 22.98 1.00 23.48 1.00 0.00 1.00 22.85 1.00 21.65 1.00 24.26 1.00 32.04 1.00 26.48 1.00 24.84 1.00 24.21 1.00 22.80 1.00 0.00 1.00 22.02 1.00 22.11 1.00 23.31 1.00 24.82 1.00 21.97 1.00 0.00 1.00 18.45 1.00 17.14 1.00 19.15 326 ATOM 3816 SD MET 1122 25.599 -20 .024 1621 .0187 16.221 1.00 18.27

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATO

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

3817 3818 3819 3820 3821 3822 'a 8o2 3 3824 3825 3826 3827 3828 3829 3830 3831 3832 3833 3834 3835 3836 3837 3838 H 3839 H 3840 3841 H 3842 H CE MET 1122 C MET 1122 o MET 1122 N VAL 1123 H VAL 1123 CA VAL 1123 CB VAL 1123 CG1 VAL 1123 CG2 VAL 11323 C VAL 1123 O VAL 1123 N ARG 1124 H ARG 1:24 CA ARG 11214 CB ARC 1124 CG ARG 1124 CD ARG 1124 NE ARG 1124 HE ARG 1124 CZ ARG 1124 NH1 ARG 1124 CHll ARC 1124 [H12 ARG 1124 NH2 ARG 1124 EH21 ARC 11:4 CH22 ARG 1:24 C ARG 1124 O ARC 1124 N ASP 1115 H ASP 1125 CA ASP 1125 CB ASP 1125 CG ASP 1:25 ODi ASP 1125 0D2 ASP 1125 C ASP 1125 O ASP 1125 N TYR 1126 24.071 -19.187 25.766 -21.255 24.772 -21.488 26.755 -20.516 27.531 -20.361 26.772 -20.019 28.184 -19.388 28.276 -18.942 28.427 -18.162 26.469 -21.191 25.512 -21.163 27.237 -22.266 27.954 -22.226 27.114 -23.478 28.229 -24.419 28.670 -25.610 30.198 -25.740 30.680 -25.911 30.151 -26.458 31.813 -25.353 32.599 -24.585 32.350 -24.406 33.435 -24.188 32.150 -25.573 31.564 -26.138 32.989 -25.172 25.742 -24.136 25.047 -24.237 25.291 -24.527 25.833 -24.328 24.018 -25.200 23.838 -25.398 22.618 -26.178 22.200 -27.129 22.095 -25.835 22.850 -24.434 21.921 -25.020 22.936 -23.104 15.883 11. 042 10.354 10.533 11.101 9.158 8.881 7.432 9.766 8.193 7 .406 8.331 9 .002 7.540 8.025 7.190 7.290 8.658 9.275 9 .121 8 .349 7 .397 8.726 10.396 10.975 10.767 7 .608 6.596 8.793 9 .586 8.971 10.479 10.965 10.297 12.031 8.347 7 .779 8 .375 1.00 11.73 1.00 17.93 1.00 14.65 1.00 19.13 1.00 0.00 1.00 26.08 1.00 28.32 1.00 29.68 1.00 28.12 1.00 27.54 1.00 28.82 1.00 29.08 1.00 0.00 1.00 32.51 1.00 34.11 1.00 34.35 1.00 37.42 1.00 44.31 1.00 0.00 1.00 46.35 1.00 44.58 1.00 0.00 1.00 0.00 1.00 41.78 1.00 0.00 1. 00 0.00 1.00 32.81 1.00 32.98 1.00 34.45 1.00 0.00 1.00 40.31 1.00 45.28 1.00 53 .34 1.00 58.74 1.00 56.41 1.00 42.48 1.00 43.18 1.00 43.78

S

S

ATOM 3843 ATOM 3844 ATOM 3845 ATOM 3846 ATOM 3847 ATOM 3848 ATOM 3849 ATOM 3850 ATOM 3851 ATOM 3852 ATOM 3853 ATOM 3854 327 S. S

S

*5S*

S.

1 5 ATOM 3855 ATOM 3856 ATOM 3857 ATOM 3858 ATOM 3859 ATOM 3860 ATOM 3861 ATOM 3863 ATOM 3864 ATOM 3865 ATOM 3866 ATOM 3867 ATOM 3868 ATOM 3869 ATOM 3870 ATOM 3871 ATOM 3872 ATOM 3873 ATOM 3874 ATOM 3875 ATOM 3876 ATOM 3877 ATOM 3878 ATOM 3879 ATOM 3880 ATOM 3881 ATOM 3882 ATOM 3883 ATOM 3884 ATOM 3885 ATOM 3886 ATOM 3887 ATOM 3888 ATOM 3889 ATOM 3889 ATOM 3891 ATOM 3892

H

CA

CB

CG

CD1 CEl CD2 Cz

OH

HH

C

0

N

H

CA

CB

CG1 CG2

C

0

N

H

CA

CB

CG

CD

NE

HE

Cz NH1 H11 HH1 2 NH2 HH2 1 HH2 2

C

0 TYR 1126 TYR 1126 TYR 1126 TYR 1126 TYR 1126 TYR 1126 TYR 1126 TYR 1126~l TYR 1126 TYR 1126 TYR 1126 TYR 1126 VAL 1126 VAL 1127 VAL 1127 VAL 1127 VAL 1127 VAL 1127 VAL 1127 VAL 1127 AL 1127 ARG 1128 ARG 1128 ARG 1128 ARG 1128 ARG 1128 ARG 1128 ARG 1128 ARG 1128 ARG 1128 ARG 1128 ARG 1128 ARG 1128 ARG 1128 ARG 1128 ARG 1128 ARG 1128 23.736 -22.681 21.869 -22.272 21.936 -20.897 21.814 -21.009 21.368 -22.198 21.340 -22.338 22.220 -19.948 21.753 -21.282 21.728 -21.434 21.465 -22.334 21.978 -22.174 20.947 -22.293 23.156 -22.080 23.975 -22.025 23.249 -22.080 24.703 -21.748 24.955 -22.021 24.935 -20.249 22.799 -23.440 22.056 -23.517 23.170 -24.522 23.800 -24.401 22.715 -25.869 23.211 -26.815 24.324 -27.807 23.765 -29.032 24.794 -30.002 25.620 -30.046 24.648 -30.839 23.554 -30.837 22.801 -30.206 23.484 -31.474 25.621 -31.699 26.455 -31.725 25.511 -32.324 21.187 -25.967 20.653 -26.862 20.433 -25.085 8 .755 7.859 8.576 10.117 10.731 12.118 10.943 12 "4 12.916 14.286 14.501 6.348 5 .687 5.722 6.260 4.256 3 .848 2 .377 4.079 3.720 2.743 4.388 5 .126 4.086 5.184 4 .876 4.161 3 .801 4.326 2.762 1.996 2 .186 1.228 2.468 3 .020 1.697 3 .988 3.328 4 .643 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0.00 45.00 49.30 56 .17 55.50 54.12 58.14 57 .E3 55.36 52.52 0.00 43 42.11 43.86 0.00 41.19 38.42 40.55 34.48 42 .71 44.92 44. 87 0.00 47.89 48.33 49 .48 52.30 55.87 0.00 57 .66 56.79 0.00 0.00 58.17 0.00 0.00 52.36 52 57 .83 ATOM 3893 N GLN 1129 328

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

3894 3895 3896 3897 3898 3899 3900 3901 3902 3903 3904 3905 3906 3907 3908 3909 3910 3911 3912 3913 3914 3915 3916 3917 3918 3919 3920 3921 3922 3923 3924 3925 3926 3927 3928 3929 3930 3931 3932

CD

OE1 NE2 HE2l HE2 2

C

0

N

H

CA

CB

OG1 HG1 CG2

C

0

N

H

CA

CB

CG

CD2 CE2 CE3

CDI

NEI

HE1 CZ2 CZ3 CH2

C

0

N

H

CA

GLN

GLN

GLN

GLN

GLN

GLN

GLN

THR

THR

THR

THR

THR

THR

THR

THR

THR

TRP

TRP

TRP

TRP

TRP

TRP

TRP

TRP

TRP

TRP

TRP

TRP

TRP

TRP

TRP

TRP

LYS

LYS

LYS

H GLN CA GLN CB GLN CG GLN 1129 1129 1129 1129 1129 1129 1129 1129 1129 1129 1129 1130 1130 1130 1130 1130 1130 1130 1130 1130 1131 1131 1131 1131 1131 1131 1131 1131 1131 1131 1131 1131 1131 1131 1131 1131 1132 1132 1132 20.853 -24.370 18.987 -25.157 18.425 -25.478 18.802 -24.439 18.109 -24.567 18.096 -25.602 17.487 -23.483 17.461 -22.696 17.131 -23.512 18.289 -23.917 17.064 -23.999 18.924 -22.761 19.871 -22.634 18.211 -21.648 18.647 -20.261 20.069 -20.145 20.285 -19.197 18.183 -20.116 18.529 -21.708 17.842 -22.402 19.601 -21.071 20.224 -20.655 19.960 -21.099 20.573 -19.749 20.672 -19.437 19.692 -19.558 20.344 -19.011 18.375 -20.015 21.824 -18.885 21.587 -18.632 22.168 -18.111 19.709 -18.910 17.731 -19.914 18.395 -19.365 20.973 -22.232 22.182 -21.998 20.440 -23.455 19.461 -23.497 21.175 -24.716 5.162 4.581 5.972 7.009 8.352 9.015 8.785 8.206 9.698 4.038 3.915 3.784 4.007 3.172 3.800 3.708 3.660 5.249 1.670 0.907 1.173 1.806 -0.236 -0.617 -2.110 -3.075 -4.192 -3.203 -2.606 -3.868 -4.465 -5.429 -4.442 -5.546 -0.317 -0.366 -0.271 -0.202 -0.242 1.00 0.00 1.00 61.29 1.00 62.70 1.00 68.83 1.00 72.83 1.00 75.79 1.00 74.31 1.00 0.00 1.00 0.00 1.00 61.62 1.00 63.97 1.00 61.19 1.00 0.00 1.00 62.61 1.00 62.24 1.00 61.26 1.00 0.00 1.00 62.20 1.00 65.28 1.00 66.03 1.00 65.49 1.00 0.00 1.00 65.51 1.00 65.52 1.00 69.50 1.00 70.86 1.00 71.04 1.00 71.56 1.00 71.98 1.00 72.22 1.00 0.00 1.00 69.81 1.00 71.09 1.00 71.65 1.00 65.31 1.00 68.03 1.00 63.74 1.00 0.00 1.00 63.56 329 ATOM 3933 CB LYS 1132 20.189 -25.850-053 10620 -0.533 1.00 62.60 ATOM 3934 CG LYS 1132 19.225 -26.249 0.555 1.00 61.93 ATOM 3935 CD LYS 1132 18.699 -27.624 0.181 1.00 62.47 ATOM 3936 CE LYS 1132 17.702 -28.156 1.197 1.00 66.22 ATOM 3937 NZ LYS 1132 16.467 -27.393 1.165 1.00 69.52 ATOM 3938 HZ1 LYS 1132 16.046 -27.465 0.217 1.00 0.00 ATOM 3939 HZ2 LYS 1132 16.673 -26.395 1.379 1.00 0.00 ATOM 3940 HZ3 LYS 1132 15 .8O0 0 -27.767 1.8uo70 v-1 .0v0 0.00 O ATOM 3941 C LYS 1132 22.422 -24.947 -1.106 1.00 65.13 1 0 ATOM 3942 0 LYS 1132 22.493 -25.877 -1.923 1.00 68.19 ATOM 3943 N LEU 1133 23.484 -24.171 -0.954 1.00 63.90 ATOM 3944 H LEU 1133 23.479 -23.489 -0.250 1.00 0.00 *04ATOM 3945 CA LEU 1133 24.674 -24.387 -1.743 1.00 63.65 *ATOM 3946 CB LEU 1133 25.465 -23.079 -1.895 1.00 64.57 1 5 ATOM 3947 CG LEU 1133 24.808 -21.770 -2.401 1.00 63.39 ATOM 3948 CD1 LEU 1133 25.918 -20.803 -2.797 1.00 60.88 *ATOM 3949 CD2 LEU 1133 23.920 -22.009 -3.616 1.00 62.28 ATOM 3950 c LEU 1133 25.426 -25.401 -0.901 1.00 65.76 000*ATOM 3951 0 LEU 1133 25.843 -25.085 0.212 1.00 68.00 ATOM 3952 N GLU 1134 25.537 -26.646 -1.361 1.00 66.71 ATOM 3953 H GLU 1134 25.157 -26.844 -2.241 1.00 0.00 ATOM 3954 CA GLU 1134 26.201 -27.707 -0.605 1.00 65.88 000ATOM 3955 CB GLU 1134 25.354 -28.997 -0.610 1.00 67.01 ATOM 3956 CG GLU 1134 23.846 -28.933 -0.907 1.00 68.05 ATOM 3957 CD GLU 1134 22.932 -28.316 0.146 1.00 69.18 ATOM 3958 OE1 GLU 1134 23.314 -27.338 0.789 1.00 69.90 ATOM 3959 0E2 GLU 1134 21.816 -28.815 0.308 1.00 67.93 ATOM 3960 c GLU 1134 27.576 -28.031 -1.190 1.00 64.86 ATOM 3961 0 GLU 1134 28.087 -27.284 -2.032 1.00 65.19 ATOM 3962 N GLY 1135 28.237 -29.113 -0.748 1.00 63.94 ATOM 3963 H GLY 1135 27.890 -29.572 0.041 1.00 0.00 ATOM 3964 CA GLY 1135 29.510 -29.581 -1.300 1.00 64.32 ATOM 3965 c GLY 1135 30.626 -28.564 -1.134 1.00 65.04 ATOM 3966 0 GLY 1135 30.865 -28.078 -0.027 1.00 69.14 ATOM 3967 N GLU 1136 31.305 -28.230 -2.232 1.00 65.55 ATOM 3968 H GLU 1136 31.118 -28.749 -3.038 1.00 0.00 ATOM 3969 CA GLU 1136 32.335 -27.183 -2.250 1.00 63.31 ATOM 3970 CB GLU 1136 33.131 -27.142 -3.579 1.00 67.04 ATOM 3971 CG GLU 1136 32.638 -27.887 -4.845 1.00 70.75 330 ATOM 3972 CD GLU 1136 31.274 -27.511 -5.428 !.00 72.63 *o S ooo.

o.

S

*o .o ATOM 3973 ATOM 3974 ATOM 3975 ATOM 3976 ATOM 3977 ATOM 3978 ATOM 3979 ATOM 3980 ATOM 3981 ATOM 3982 ATOM 3983 ATOM 3984 ATOM 3985 1 5 ATOM 3986 ATOM 3987 ATOM 3988 ATOM 3989 ATOM 3990 ATOM 3991 ATOM 3992 ATOM 3993 ATOM 3994 ATOM 3995 ATOM 3996 ATOM 3997 ATOM 3998 ATOM 3999 ATOM 4000 ATOM 4001 ATOM 4002 ATOM 4003 ATOM 4004 ATOM 4005 ATOM 4006 ATOM 4007 ATOM 4008 ATOM 4009

OEJ

OE2

C

0

N

H

CA

CB

C

0

N

H

CA

CB

CG

CD1 CD2

C

0

N

H

CA

CB

CG

CD

OE1 OE2

C

0

N

H

CA

CB

CG

CD

OE1 NE2 1 GLU 1136 2 GLU 1136 GLU 1136 GLU 1136 ALA 1137 ALA 1137 ALA 1137 ALA 1137 ALA 1137 ALA 1137 LEU 1138 LEU 1138 LEU 1138 LEU 1138 LEU 1138 LEU 1138 LEU 1138 LEU 1138 LEU 1138 GLU 1139 GLU 1139 GLU 1139 GLU 1139 GLU 1139 GLU 1139 GLU 1139 GLU 11239 GLU 1139 GLU 1139 GLN 1140 GLN 1140 GLN 1140 GLN 1140 GLN 1140 GLN 1140 GLN 1140 GLN 1140 30.272 -28.090 31.218 -26.661 31.703 -25.810 32.147 -24.983 30.581 -25.625 30.196 -26.378 29.850 -24.377 28.617 -24.541 29.446 -23.931 29.361 -22.731 29.238 -24.894 29.212 -25.815 28.985 -24.630 28.623 -25.949 28.039 -26.034 26.745 -25.238 27.782 -27.510 30.257 -24.016 30.199 -22.866 31.421 -24.691 31.407 -25.596 32.702 -24.191 33.815 -25.131 35.261 -24.889 36.311 -25.774 36.544 -25.580 36.899 -26.646 32.984 -22.739 33.420 -21.921 32.682 -22.377 32.365 -23.071 32.876 -21.003 32.967 -20.930 31.674 -20.780 31.587 -21.593 32.482 -22.341 30.460 -21.524 29.726 -20.982 -4.999 -6.321 -2.070 -1.268 -2.766 -3.254 -2.767 -3.663 -1.362 -1.087 -0.464 -0.787 0.947 1.639 3 .047 3 .210 3.310 1.541 1.993 1 .488 1 .112 2 .000 1 .497 1.948 1.269 0 .074 1 .924 1.587 2 .417 0.325 -0.297 -0.136 -1.681 -2.496 -3.783 -4.178 -4.480 -4.126 1.00 72.08 1.00 72.72 1.00 58.99 1.00 56.93 i.00 56.11 i. 00 0.00 !.00 56.06 !.00 55.23 1.00 55.98 1.00 54.23 i..00 57.71 1.00 0.00 .00 60.29 1.00 55.39 1.00 54.97 1.00 49.34 1.00 52.82 1.00 61.97 1.00 62.86 1.00 61.86 1.00 0.00 1.00 62.74 1.00 61.24 .00 57.30 1.00 55.83 1.00 57.77 1.00 50.09 1.00 65.63 1.00 66.43 1.00 65.95 1.00 0.00 1.00 66.03 1.00 67.56 1.00 72.83 1.00 77.61 1.00 79.83 1.00 79.79 1.00 0.00 ATOM 4010 HE21 GLN 1140 331 ATOM 4011 HE22 GLN 1140 30.439 -22.013 -5.326 1.00 0.00 ATOM 4012 C GLN 1140 31.738 -20.111 0.344 1.00 65.43 ATOM 4013 0 GLN 1140 32.001 -18.966 0.717 1.00 65.89 ATOM 4014 N ALA 1141 30.484 -20.593 0.404 1.00 64.48 ATOM 4015 H ALA 1141 30.331 -21.536 0.181 1.00 0.00 ATOM 4016 CA ALA 1141 29.327 -19.805 0.819 1.00 63.19 ATOM 4017 CB ALA 1141 28.077 -20.670 0.840 1.00 60.31 ATOM 4018 C AL.A 114 1. 29.515 -19.218 2.0 1.00 61.63 ATOM 4019 0 ALA 1141 29.156 -18.073 2.488 1.00 60.18 ATOM 4020 N ILE 1142 30.160 -20.006 3.067 1.00 61.25 ATOM 4021. H ILE 1142 30.402 -20.903 2.746 1.00 0.00 ATOM 4022 CA ILE 1142 30.484 -19.641 4.435 1.00 59.83 so.ATOM 4023 CB ILE 1142 31.157 -20.900 5.095 1.00 60.04 ATOM 4024 CG2 ILE 1142 32.084 -20.514 6.259 1.00 63.09 sees 15 ATOM 4025 CG1 ILE 1142 30.076 -21.816 5.665 1.00 58.69 see* ATOM 4026 CD ILE 1142 29.000 -22.397 4.736 1.00 54.31 *ATOM 4027 C ILE 1142 31.367 -18.397 4.469 1.00 59.27 ATOM 4028 0 ILE 1142 31.114 -17.476 5.251 1.00 57.70 *ATOM 4029 N ILE 1143 32.397 -18.305 3.631 1.00 60.19 ATOM 4030 H ILE 1143 32.567 -19.013 2.972 1.00 0.00 ATOM 4031 CA ILE 1143 33.242 -17.128 3.679 1.00 61.81 e*ATOM 4032 CB ILE 1143 34.659 -17.470 3.078 1.00 64.29 e~.ATOM 4033 CG2 ILE 1143 34.620 -17.636 1.554 1.00 63.53 ATOM 4034 CG1 ILE 1143 35.640 -16.335 3.454 1.00 66.15 ATOM 4035 CD ILE 1143 35.960 -16.121 4.963 1.00 61.98 ATOM 4036 C ILE 1143 32.552 -15.992 2.941 1.00 61.53 ATOM 4037 0 ILE 1143 32.769 -14.816 3.240 1.00 62.25 ATOM 4038 N SER 1144 31.642 -16.318 2.030 1.00 63.73 ATOM 4039 H SER 1144 31.415 -17.258 1.876 1.00 0.00 ATOM 4040 CA SER 1144 30.940 -15.310 1.265 1.00 64.99 ATOM 4041 CEB SER 1144 30.516 -15.998 -0.048 1.00 65.52 ATOM 4042 OG SER 1144 31.608 -16.655 -0.702 1.00 60.59 ATOM 4043 HG SER 1144 32.049 -17.235 -0.076 1.00 0.00 ATOM 4044 C SER 1144 29.758 -14.731 2.067 1.00 65.32 ATOM 4045 0 SER 1144 28.634 -14.623 1.559 1.00 68.14 ATOM 4046 N GLN 1145 29.938 -14.325 3.335 1.00 63.50 ATOM 4047 H GLN 1145 30.843 -14.279 3.712 1.00 0.00 ATOM 4048 CA GLN 1145 28.809 -13.809 4.091 1.00 60.48 ATOM 4049 CB GLN 1145 28.723 -14.494 5.452 1.00 56.62 332 ATOM 4050 CG GLN 1145 28.142 -15.910 529 10 5.299 1.00 53.05 ATOM 4051 CD GLN 1145 26.825 -16.090 4.524 1.00 51.72 ATOM 4052 OE. GLN 1145 25.802 -15.428 4.735 1.00 53.41 ATOM 4053 NE2 GLN 1145 26.771 -17.024 3.593 1.00 46.83 ATOM 4054 HE21 GLN 1145 27.582 -17.547 3.429 1.00 0.00 ATOM 4055 HE22 GLN 1145 25.935 -17.136 3.098 1.00 0.00 ATOM 4056 c GLN 1145 28.790 -12.311 4.280 1.00 58.63 ATOM 4057 0 GLN 1145 29.778 -11.635 4.576 1.00 56.87 ATOM 4058 N ALA 1146 27.578 -11.849 3.981 1.00 59.12 1 0 ATOM 4059 H ALA 1146 26.897 -12.510 3.738 1.00 0.00 ATOM 4060 CA ALA 1146 27.193 -10.451 4.009 1.00 62.34 ATOM 4061 CB ALA 1146 25.679 -10.365 3.809 1.00 59.64 9ATOM 4062 c ALA 1146 27.582 -9.759 5.314 1.00 65.19 ATOM 4063 0 ALA 1146 27.167 -10.223 6.375 1.00 68.05 1 5 ATOM 4064 N PRO 1147 28.322 -8.645 5.329 1.00 66.24 ATOM 4065 CD PRO 1147 28.322 -7.661 4.250 1.00 68.36 ***ATOM 4066 CA PRO 1147 29.113 -8.166 6.468 1.00 65.49 ATOM 4067 CB PRO 1147 29.549 -6.786 6.027 1.00 66.85 ATOM 4068 CG PRO 1147 29.610 -6.907 4.523 1.00 68.63 ATOM 4069 c PRO 1147 28.493 -8.163 7.871 1.00 63.34 ATOM 4070 0 PRO 1147 29.080 -8.699 8.816 1.00 61.92 *'*ATOM 4071 N GLN 1148 27.298 -7.605 8.089 1.00 59.39 ATOM 4072 H GLN 1148 26.805 -7.235 7.326 1.00 0.00 ATOM 4073 CA GLN 1148 26.750 -7.591 9.436 1.00 54.07 25 ATOM 4074 CB GLN 1148 25.679 -6.484 9.581 1.00 54.31 **ATOM 4075 CG GLN 1148 24.390 -6.516 8.766 1.00 56.67 ATOM 4076 CD GLN 1148 24.445 -5.927 7.356 1.00 56.23 ATOM 4077 OE1 GLN 1148 25.198 -6.360 6.475 1.00 57.34 ATOM 4078 NE2 GLN 1148 23.635 -4.917 7.079 1.00 51.65 ATOM 4079 HE21 GLN 1148 23.090 -4.554 7.811 1.00 0.00 ATOM 4080 HE22 GLN 1148 23.553 -4.591 6.160 1.00 0.00 ATOM 4081 C GLN 1148 26.164 -8.929 9.884 1.00 50.94 ATOM 4082 0 GLN 1148 25.824 -9.064 11.061 1.00 47.58 ATOM 4083 N VAL 1149 26.097 -9.991 9.063 1.00 49.04 ATOM 4084 H VAL 1149 26.493 -9.940 8.168 1.00 0.00 ATOM 4085 CA VAL 1149 25.492 -11.239 9.524 1.00 45.67 ATOM 4086 CB VAL 1149 25.1146 -12.262 8.372 1.00 41.33 ATOM 4087 CG1 VAL 1149 24.379 -11.486 7.327 1.00 44.52 ATOM 4088 CG2 VAL 1149 26.342 -12.968 7.782 1.00 37.34 333 ATOM 4089 C VAL 1149 26.393 -11.954 10.518 1.00 43.99 ATOM 4090 0 VAL 1149 25.900 -12.667 11.386 1.00 41.36 ATOM 4091 N GLU 1150 27.705 -11.733 10.479 1.00 42.85 ATOM 4092 H GLU 1150 28.054 -11.109 9.808 1.00 0.00 ATOM 4093 CA GLU 1150 28.618 -12.389 11.398 1.00 42.22 ATOM 4094 CB GLU 1150 30.050 -12.009 11.046 1.00 46.21 ATOM 4095 CG GLU 1150 30.495 -12.414 9.621 1.00 57.47 ATOM 4096 CD GLU 1150 30.205 -11.422 8.7 1.00 620 ATOM 4097 OE1 GU 1150 31.050 -10.572 8.182 1.00 67.14 ATOM 4098 0E2 GLU 1150 29.142 -11.493 7.865 1.00 61.78 ATOM 4099 C GLU 1150 28.255 -11.931 12.803 1.00 38.38 ATOM 4100 0 GLU 1150 27.993 -12.741 13.689 1.00 42.57 ~.:ATOM 4101 N LYS 1151 28.058 -10.619 12.937 1.00 35.01 ATOM 4102 H LYS 1151 28.150 -10.069 12.135 1.00 0.00 1 5 ATOM 4103 CA LYS 1151 27.642 -9.981 14.175 1.00 30.94 *ATOM 4104 CB LYS 1151 27.567 -8.423 14.081 1.00 34.99 :::ATOM 4105 CG LYS 1151 28.827 -7.591 13.773 1.00 39.28 ATOM 4106 CD LYS 1151 29.258 -7.778 12.320 1.00 44.76 ATOM 4107 CE LYS 1151 30.649 -7.256 12.041 1.00 47.25 ATOM 4108 NZ LYS 1151 31.121 -7.818 10.788 1.00 45.73 ATOM 4109 HZ1 LYS 1151 30.467 -7.579 10.016 1.00 0.00 ATOM 4110 HZ2 LYS 1151 31.179 -8.852 10.886 1.00 0.00 ATOM 4111 HZ3 LYS 1151 32.067 -7.440 10.576 1.00 0.00 ATOM 4112 C LYS 1151 26.241 -10.466 14.517 1.00 25.99 ATOM 4113 0 LYS 1151 25.943 -10.676 15.685 1.00 27.16 ATOM 4114 N LEU 1152 25.357 -10.684 13.540 1.00 22.11 ATOM 4115 H LEU 1152 25.620 -10.478 12.621 1.00 0.00 ATOM 4116 CA LEU 1152 23.993 -11.114 13.813 1.00 16.23 ATOM 4117 CB LEU 1152 23.177 -10.957 12.515 1.00 9.86 ATOM 4118 CG LEU 1152 22.906 -9.504 12.080 1.00 11.37 ATOM 4119 CD1 LEU 1152 22.338 -9.492 10.678 1.00 9.78 ATOM 4120 CD2 LEU 1152 21.910 -8.841 13.005 1.00 11.47 ATOM 4121 C LEU 1152 23.896 -12.523 14.371 1.00 10.24 ATOM 4122 0 LEU 1152 23.131 -12.774 15.299 1.00 9.17 ATOM 4123 N ILE 1153 24.727 -13.419 13.841 1.00 13.04 ATOM 4124 H ILE 1153 25.319 -13.098 13.132 1.00 0.00 ATOM 4125 CA ILE 1153 24.864 -14.828 14.218 1.00 12.12 ATOM 4126 CB ILE 1153 25.744 -15.474 13.121 1.00 15.18 ATOM 4127 CG2 ILE 1153 26.453 -16.748 13.547 1.00 14.74 334 oo

ATOM

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ATOM

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ATOM

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ATOM

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ATOM

4128 4129 4130 4131 4132 4133 4134 4136 4137 4138 4139 4140 4141 4142 4143 4144 4145 4146 4147 4148 4149 4150 4151 4152 4153 4154 4155 4156 4157 4158 4159 4160 4161 4162 4163 4164 4165 4166 CG1 ILE CD ILE C ILE 0 ILE N ALA H ALA CA ALA CB ALA C ALA N ALA N THR H THR CA THR CB THR OGI THR HG1 THR CG2 THR C THR O THR N THR H THR CA THR CB THR OGI THR HG1 THR CG2 THR C THR O THR N ALA H ALA CA ALA CB ALA C ALA O ALA N HIS H HIS CA HIS CB HIS CG HIS 1153 1153 1153 1153 1154 1154 1154 1154 1154 1154 1155 1155 1155 1155 1155 1155 1155 1155 1155 1156 1156 1156 1156 1156 1156 1156 1157 1157 1157 1157 1157 1157 1157 1158 1158 1158 1158 1158 24.803 -15.737 25.554 -16.002 25.457 -14.936 24.938 -15.653 26.552 -14.241 27.021 -13.803 27.123 -14.168 28.259 -13.194 26.107 -13.747 25.901 -14.458 25.380 -12.645 25.577 -12.028 24.349 -12.242 23.904 -10.801 25.086 -9.989 25.450 -9.946 22.905 -10.096 23.190 -13.272 22.481 -13.310 22.963 -14.161 23.450 -14.028 21.961 -15.233 21.500 -15.438 20.596 -14.388 19.941 -14.355 20.799 -16.746 22.487 -16.548 21.664 -17.362 23.812 -16.756 24.421 -16.012 24.391 -18.060 25.908 -17.958 23.912 -18.755 23.814 -19.974 23.520 -17.991 23.688 -17.032 22.988 -18.518 22.621 -17.348 21.657 -16.322 11.964 10.657 15.614 16.468 15.879 15.135 17.201 11. 1 A 18.276 19.281 18.103 17.358 19.065 18.598 18.654 19.545 19.487 19.190 20.208 18.207 17.364 18.199 16.684 16.386 17.088 16.399 18.816 19.249 18.993 18.786 19.349 19.445 20.604 20.635 21.622 21.526 22.860 23.802 23.213 1.00 15.60 1.00 27.01 1.00 12.01 1.00 12.84 1.00 10.22 1.00 0.00 1.00 11.63 L.UU O.O 1.00 18.06 1.00 22.58 1.00 17.52 1.00 0.00 1.00 18.83 1.00 22.02 1.00 25.75 1.00 0.00 1.00 26.93 1.00 20.86 1.00 18.89 1.00 21.15 1.00 0.00 1.00 18.52 1.00 19.00 1.00 18.19 1.00 0.00 1.00 21.79 1.00 15.90 1.00 13.44 1.00 15.78 1.00 0.00 1.00 13.25 1.00 7.54 1.00 13.91 1.00 15.61 1.00 14.45 1.00 0.00 1.00 10.20 1.00 8.12 1.00 8.39 335 ATOM 4167 CD2 HIS 1158 20.290 -16.362 2.3 .0 44 23.334 1.00 4.48

ATOM

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ATOM

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4168 4169 4170 4171 4172 4173 A.L4 I A& 4175 4176 4177 4178 4179 4180 4181 4182 4183 4184 4185 4186 4187 4188 4189 4190 4191 4192 4193 4194 NDi HIS HD1 HIS CEl HIS NE2 HIS HE2 HIS C HIS 0 HIS N GLU H GLU CA GLU CB GLU CG GLU CD GLU QEl GLU 0E2 GLU C GLU O GLU N ARC H ARC CA ARC CB ARG CG ARC CD ARG NE ARG HE ARC CZ ARG NHI ARG 1158 1158 1158 1158 1158 1158 1158 1159 1159 1159 1159 1159 1159 1159 1159 1159 1159 1160 1160 1160 1160 1160 1160 1160 1160 1160 1160 1160 1160 1160 1160 1160 1160 1160 1161 1161 1161 1161 21.946 -15.266 22.832 -14.924 20.813 -14.687 19.829 -15.355 18.888 -15.059 21.781 -19.429 20.960 -19.294 21.217 -18.718 19.753 -20.112 18.877 -19.607 18.247 -18.240 17.302 -17.760 17.281 -18.339 16.581 -16.790 19.979 -21.585 19.147 -22.458 21.159 -21.818 21.803 -21.086 21.574 -23.139 22.616 -23.065 22.364 -22.145 21.047 -22.440 20.988 -23.796 21.639 -24.458 20.070 -24.189 19.143 -23.355 19.110 -22.401 18.471 -23.690 20.066 -25.468 20.734 -26.107 19.398 -25.781 22.214 -23.843 22.669 -24.984 22.309 -23.215 21.769 -22.422 23.045 -23.835 23.790 -22.792 22.462 22.195 22.128 22.654 22.617 22.688 21.636 20.883 21. 496 20.388 20.637 19 .540 18.449 19 .788 21.214 21.491 20.657 20.550 20.254 19.111 17.916 17 .215 16.705 17.019 15. 816 15 .329 15.626 14.669 15 .428 15.803 14.752 21.437 21.293 22.614 22. 814 23 .701 24.485 1.00 8.59 1.00 0.00 1.00 5.15 1.00 6.40 1.00 0.00 1.00 14.20 1. 00 15.95 1.00 18.68 1.00 0.00 1.00 20.00 1.00 24.35 1.00 31.35 1.00 32.75 1.00 32.14 1.00 38.48 1.00 23.06 1.00 23.92 1.00 25.06 1.00 0.00 1.00 29.23 1.00 30.90 1.00 31.60 1.00 35.44 1.00 41.49 1.00 0.00 1.00 44.62 1.00 48.17 1.00 0.00 1.00 0.00 1.00 46.65 1.00 0.00 1.00 0.00 1.00 27.73 1.00 30.26 1.00 25.32 1.00 0.00 1.00 18.76 1.00 11.53 ATOM 4195 HH11 ARC ATOM 4196 HH12 ARC ATOM 4197 NH2 ARC ATOM 4198 HH21 ARC ATOM 4199 HH22 ARG ATOM 4200 C ARC ATOM 4201 0 ARC ATOM 4202 N MET ATOM 4203 H MET ATOM 4204 CA MET ATOM 4205 CB MET 336

C

C.

C

C

C

ATOM

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1 5 ATOM

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25 ATOM

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4206 CG MET 4207 SD MET 4208 CE MET 4209 c MET 4210 0 MET 4211 N PRO 4212 CD PRO 4213 CA PRO 4214 CB PRO 4215 CG PRO 4216 c PRO 4217 0 PRO 4218 N TRP 4219 H TRP 4220 CA TRP 4221 CB TRP 4222 CG TRP 4223 CD2 TRP 4224 CE2 TRP 4225 CE3 TRP 4226 CD1 TRP 4227 NEl TRP 4228 HEl TRP 4229 CZ2 TRP 4230 CZ3 TRP 4231 CH2 TRP 4232 c TRP 4233 0 TRP 4234 N TYR 4235 H TYR 4236 CA TYR 4237 CB TYR 4238 CG TYR 4239 CD1 TYR 4240 CEl TYR 4241 CD2 TYR 4242 CE2 TYR 4243 CZ TYR 1161 1161 1161 1161 1161 1162 1162 1162 1162 1162 1162 1162 1163 1163 1163 1163 1163 1163 1163 1163 1163 1163 1163 1163 1163 1163 1163 1163 1164 1164 1164 1164 1164 1164 1164 1164 1164 1164 24.778 -22.042 25.964 -23.089 27.076 -23.610 22.056 -24.545 20.927 -24.071 22.425 -25.665 23.679 -26.372 21.579 -26.392 22.456 -27.563 23.862 -27.082 21.044 -25.611 20.058 -25.944 21.718 -24.527 22.473 -24.268 21.372 -23.683 22.663 -23.045 23.679 -22.401 23.669 -21.123 24.925 -21.090 22.844 -19.996 24.838 -23.082 25.575 -22.263 26.499 -22.436 25.363 -19.959 23.282 -18.873 24.533 -18.845 20.345 -22.622 19.793 -22.041 19.988 -22.349 20.226 -22.947 19.053 -21.280 19.387 -20.582 18.493 -19.365 18.541 -18.245 17.687 -17.155 17.602 -19.386 16.756 -18.301 16.806 -17.192 15.993 -16.110 23.647 1.00 13.13 22.771 1.00 26.11 24.041 1.00 21.15 24.593 1.00 12.35 24.734 1.00 12.85 25.233 1.00 12.69 24.996 1.00 9.78 26.190 1.00 10.28 26.550 1.00 9.48 26.321 1.00 10.73 27.407 1.00 9.82 28.062 1.00 12.50 27.743 1.00 11.52 27.184 1.00 0.00 28.862 1.00 10.72 29.405 1.00 4.48 28.454 1.00 4.54 27.880 1.00 5.04 27.255 1.00 5.29 27.775 1.00 2.00 28.176 1.00 2.28 27.457 1.00 6.80 27.155 1.00 0.00 26.540 1.00 6.60 27.055 1.00 2.00 26.441 1.00 2.00 28.520 1.00 11.70 29.456 1.00 11.21 27.258 1.00 12.21 26.519 1.00 0.00 26.979 1.00 9.05 25.667 1.00 11.55 25.402 1.00 9.69 26.254 1.00 8.89 26.012 1.00 12.44 24.314 1.00 8.85 24.069 1.00 8.29 24.921 1.00 13.30 24.673 1.00 15.18 ATOM 4244 OH TYR 1164 337 a a 9 a. a a a a

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1 5 ATOM

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4245 4246 4247 4248 4249 4250 4251 A n 4253 4254 4255 4256 4257 4258 4259 4260 4261 4262 4263 4264 4265 4266 4267 4268 4269 4270 4271 4272 4273 4274 4275 4276 4277 4278 4279 4280 4281 4282 4283 HH TYR C TYR 0 TYR N HIS

HIS

CA HIS CB HIS CG. HISL.

CD2 HIS ND1 HIS HD1 HIS CE1 HIS NE2 HIS HE2 HIS C HIS O HIS N SEP.

H SEP.

CA SEP.

CB SER OG SEP.

HG SEP.

C SER o SEP.

N SEP.

H SER CA SER CB SEP.

OG SEP.

HG SEP.

C SEP.

O SEP.

N LEU H LEO CA LEO CB LEU CG LEO CD1 LEO CD2 LEO 1164 1164 1164 1165 1165 1165 1165 11651 1165 1165 1165 1165 1165 1165 1165 1166 1166 1166 1166 1166 1166 1166 1167 1167 1167 1167 1167 1167 1167 1167 1168 1168 1168 1168 1168 1168 1168 15.388 -16.300 17.676 -21.864 17.449 -22.907 16.757 -21.238 17.023 -20.453 15.386 -21.680 15.046 -22.242 17.188 -23.531 15.360 -24.673 14.432 -24.992 16.389 -25.423 17.481 -24.727 18.390 -25.104 14.499 -20.488 14.122 -19.735 14.123 -20.310 14.377 -20.990 13.275 -19.235 13.142 -19.448 12.997 -20.850 13.693 -21.116 11.883 -19.119 11.229 -18.073 11.484 -20.297 12.094 -21.052 10.186 -20.640 9.981 -22.064 11.206 -22.853 11.021 -23.626 9.887 -20.535 8.729 -20.731 10.815 -20.231 11.680 -19.865 10.498 -20.295 11.557 -21.101 12.002 -22.465 13.095 -22.977 10.868 -23.462 23.946 26. 897 26.271 27.625 28. 157 27. 657 29.025 29 .470 29. 603 29.834 29. 833 30.172 30.026 30.044 27.359 28.246 26.096 25.433 25.580 24.077 23.816 23.199 26.201 26.253 26.640 26.534 27.174 26.593 26.583 26.039 28.688 29.066 29.614 29.328 31. 044 31.794 31. 275 32.202 31.244 1.00 0.00 1.00 13.42 1.00 16.65 1.00 10.41 1.00 0.00 1.00 9.19 1.00 8.07 1.00 3.28 1.00 5.83 1.00 0.00 1.00 2.00 1.00 3.94 1.00 0.00 1.00 12.21 1.00 15.69 1.00 18.69 1.00 0.00 1.00 22.32 1.00 24.30 1.00 27.37 1.00 0.00 1.00 25.68 1.00 28.35 1.00 28.43 1.00 0.00 1.00 30.35 1.00 35.08 1.00 35.86 1.00 0.00 1.00 27.36 1.00 25.18 1.00 24.64 1.00 0.00 1.00 22.29 1.00 19.48 1.00 19.31 1.00 21.06 1.00 14.54 338 ATOM 4284 C LEU 1168 10.306 -19.012 31.834 1.00 17.29 ATOM 4285 0 LEU 1168 11.015 -18.020 31.664 1.00 18.35 ATOM 4286 N THR 1169 9.313 -19.044 32.722 1.00 18.42 ATOM 4287 H THR 1169 8.737 -19.830 32.790 1.00 0.00 ATOM 4288 CA THR 1169 9.095 -17.971 33.682 1.00 17.82 ATOM 4289 CB THR 1169 7.653 -17.980 34.221 1.00 19.72 ATOM 4290 OGI THR 1169 7.429 -19.264 34.804 1.00 19.56 ATOM 4291 HGi THR 1169 6.475 -19.419 34.793 1.00 0.00 ATOM 4292 CG2 THR 1169 6.636 -17.685 33.152 1.00 18.55 1 0 ATOM 4293 C THR 1169 10.043 -18.209 34.852 1.00 10.98 ATOM 4294 0 THR 1169 10.641 -19.285 34.937 1.00 13.16 ATOM 4295 N ARG 1170 10.164 -17.270 35.781 1.00 12.27 ATOM 4296 H ARG 1170 9.759 -16.397 35.585 1.00 0.00 *o o ATOM 4297 CA ARG 1170 10.945 -17.431 36.998 1.00 13.63 1 5 ATOM 4298 CB ARG 1170 10.726 -16.204 37.885 1.00 9.48 ATOM 4299 CG ARG 1170 11.337 -16.386 39.259 1.00 11.46 ATOM 4300 CD ARG 1170 10.964 -15.269 40.208 1.00 11.17 ATOM 4301 NE ARG 1170 11.912 -14.216 39.978 1.00 15.66 ATOM 4302 HE ARG 1170 11.832 -13.703 39.151 1.00 0.00 20 ATOM 4303 CZ ARG 1170 12.818 -13.829 40.866 1.00 13.85 ATOM 4304 NH1 ARG 1170 13.634 -12.864 40.468 1.00 13.48 ATOM 4305 HH11 ARG 1170 13.543 -12.488 39.546 1.00 0.00 oooo ATOM 4306 HH12 ARG 1170 14.351 -12.528 41.072 1.00 0.00 ATOM 4307 NH2 ARG 1170 12.878 -14.317 42.111 1.00 15.64 25 ATOM 4308 HH21 ARG 1170 12.202 -14-988 42.417 1 .00 0.00 ATOM 4309 HH22 ARG 1170 13.578 -13.986 42.747 1.00 0.00 ATOM 4310 C ARG 1170 10.584 -18.709 37.768 1.00 14.28 ATOM 4311 0 ARG 1170 11.437 -19.520 38.145 1.00 15.79 ATOM 4312 N GLU 1171 9.292 -18.934 37.913 1.00 12.16 ATOM 4313 H GLU 1171 8.675 -18.340 37.445 1.00 0.00 ATOM 4314 CA GLU 1171 8.792 -20.075 38.632 1.00 16.73 ATOM 4315 CB GLU 1171 7.269 -20.067 38.688 1.00 24.50 ATOM 4316 CG GLU 1171 6.607 -18.830 39.300 1.00 39.58 ATOM 4317 CD GLU 1171 6.664 -17.554 38.452 1.00 46.40 ATOM 4318 OE1 GLU 1171 7.176 -16.541 38.935 1.00 48.99 ATOM 4319 OE2 GLU 1171 6.203 -17.579 37.308 1.00 53.13 ATOM 4320 C GLU 1171 9.232 -21.344 37.952 1.00 16.53 ATOM 4321 0 GLU 1171 9.811 -22.204 38.602 1.00 19.25 ATOM 4322 N GLU 1172 9.021 -21.438 36.633 1.00 20.89 339 ATOM 4323 H GLU 1172 8.697 -20.643 3.5 .0 C0 36.157 1.00 0.00

S

S.

S.

ATOM 4324 ATOM 4325 ATOM 4326 ATOM 4327 ATOM 4328 ATOM 4329 ATOM 4330 ATOM 4331 1 0 ATOM 4332 ATOM 4333 ATOM 4334 ATOM 4335 ATOM 4336 1 5 ATOM 4337 ATOM 4338 ATOM 4339 ATOM 4340 ATOM 4341 ATOM 4342 ATOM 4343 ATOM 4344 ATOM 4345 ATOM 4346 25 ATOM 4347 ATOM 4348 ATOM 4349 ATOM 4350 ATOM 4351 ATOM 4352 ATOM 4353 ATOM 4354 ATOM 4355 ATOM 4356 3 5 ATOM 4357 ATOM 4358 ATOM 4359 ATOM 4360 ATOM 4361 CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU 0 GLU N ALA H ALA CA ALA CB ALA C ALA O ALA N GLU H GLU CA GLU CB GLU CG GLU CD CLU OE1 GLU 0E2 GLU C GLU o GLU N ARG H ARG CA ARC CB ARG CC ARG CD ARG NE ARC HE ARG CZ ARC NH1 ARG HH11 ARC HH12 ARG NH2 ARG HH21 ARG 1172 1172 1172 1172 1172 1172 1172 1173 1173 1173 1173 1173 1173 1174 1174 1174 1174 1174 1174 1174 1174 1174 1174 1175 1175 1175 1175 1175 1175 1175 1175 1175 1175 1175 1175 1175 1175 9.338 -22.632 8.892 -22.458 7.369 -22.486 6.780 -21.903 7.359 -22.058 5.723 -21.282 10 81 2.927 11.207 -24.083 11.643 -21.889 11.266 -20.991 13.088 -22.029 13.744 -20.657 13.504 -22.681 14.228 -23.673 13.008 -22.180 12.387 -21.420 13.300 -22.759 12.528 -22.007 12.963 -20.560 12.413 -19.797 11.503 -20.278 12.902 -18.701 12.906 -24.235 13.703 -25.090 11.703 -24.578 11.118 -23.863 11.240 -25.958 9.812 -26.015 8.805 -25.491 7.351 -25.744 6.593 -24.512 6.444 -23.921 6.092 -24.160 6.260 -24.923 6.773 -25.779 5.870 -24.633 5.419 -23.010 5.312 -22.413 35.849 34.416 34.271 32.984 31. 915 33.052 35.866 35.976 35.819 35.737 35.894 35.803 37.208 37.220 38.330 38.258 39.637 40.702 40.838 42.032 42.705 42.293 39.680 40.077 39.198 38.863 39.149 38.618 39.647 39.250 39.055 39.823 37.862 36.776 36.831 35.902 37.746 38.541 1.00 17.91 1.00 17.90 1.00 27.69 1.00 27.08 1.00 34.51 1.00 32.11 1.00 18.39 1.00 17.72 1.00 0.00 1.00 17.23 1.00 16.89 1.00 14.94 1.00 17. 02 1.00 15.36 1.00 0.00 1.00 15.72 1.00 14.38 1.00 17.68 1.00 20.98 1.00 28.76 1.00 17.73 1.00 17.50 1.00 15.79 1.00 19 .83 1.00 0.00 1.00 19.46 1.00 22.12 1.00 31.07 1.00 37.43 1.00 40.92 1.00 0.00 1.00 43.85 1.00 44.41 1.00 0.00 1.00 0.00 1.00 41.58 1.00 0.00

S*

S

340 ATOM 4362 HH22 ARG 1175 5.048 -22.735 3.6 .0 00 36.860 1.00 0.00 .aa.aa a ATOM 4363 ATOM 4364 ATOM 4365 ATOM 4366 ATOM 4367 ATOM 4368 ATOM 4369 ATOM 4370 1 0 ATOM 4371 ATOM 4372 ATOM 4373 ATOM 4374 ATOM 4375 1 5 ATOM 4376 ATOM 4377 ATOM 4378 ATOM 4379 ATOM 4380 ATOM 4381 ATOM 4382 ATOM 4383 ATOM 4384 ATOM 4385 ATOM 4386 ATOM 4387 ATOM 4388 ATOM 4389 ATOM 4390 ATOM 4391 ATOM 4392 ATOM 4393 ATOM 4394 ATOM 4395 ATOM 4396 ATOM 4397 ATOM 4398 ATOM 4399 ATOM 4400 C ARG O ARG N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS o LYS N LEU H LEU CA LEU CB LEU CG LETJ CD1 LEU CD2 LEU C LEU o LEU N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CEl TYR CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR C TYR 0 TYR 1175 1175 1176 1176 1176 1176 1176 1176 1176 1176 1176 1176 1176 1176 1176 1177 1177 1177 1177 1177 1177 1177 1177 1177 1178 1178 1178 1178 1178 1178 1178 1178 1178 1178 1178 1178 1178 1178 12.139 -26.831 12.465 -27.951 12.646 -26.307 12.409 -25.382 13.523 -27.040 13.704 -26.240 14.239 -27.027 13.192 -27.947 12.084 -27.187 11.254 -28.098 10.824 -28.804 11.850 -28.586 10.508 -27.570 14.866 -27.273 15.351 -28.400 15.433 -26.223 14.945 -25.377 16.715 -26.242 17.004 -24.782 18.184 -23.971 18.762 -24.564 17.697 -22.560 16.744 -27.158 17.759 -27.761 15.637 -27.251 14.887 -26.668 15.521 -28.151 14.301 -27.775 14.517 -26.530 15.626 -26.436 15.821 -25.289 13.605 -25.479 13.795 -24.326 14.906 -24.231 15.105 -23.078 14.279 -22.583 15.397 -29.624 15.565 -30.502 38.290 38.681 37.179 36.946 36. 277 34. 968 33.766 33.130 32. 375 31.601 32.232 30.900 31.106 36.941 36.968 37.531 37.490 38.225 38.564 38.029 36.777 37.810 39.461 39.804 40.193 39.963 41. 329 42.188 43.029 43 .875 44.649 42.958 43.729 44.576 45.334 45.370 40. 939 41.793 1.00 18.03 1.00 19.18 1.00 19.95 1.00 0.00 1.00 19.66 1.00 24.70 1.00 27.63 1.00 33.14 1.00 32.52 1.00 30.45 1.00 0.00 1.00 0.00 1.00 0.00 1.00 15.53 1.00 18.60 1.00 20.13 1.00 0.00 1.00 18.75 1.00 17.17 1.00 15.05 1.00 13.44 1.00 7.89 1.00 17.88 1.00 16.88, 1.00 19.77 1.00 0.00 1.00 24.93 1.00 22.12 1.00 24.04 1.00 25.26 1.00 29.64 1.00 20.32 1.00 25.80 1.00 28.67 1.00 28.90 1.00 0.00 1.00 27.89 1.00 28.32 341 ATOM 4401 N SER 1179 15.080 -29.931 39.671 1.00 30.11

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

4402 4403 4404 4405 4406 4407 4408 4409 4410 4411 4412 4413 4414 4415 4416 4417 4418 4419 4420 4421 4422 4423 4424 4425 4426 4427

SER

SER

SER

SER

SER

SER

SER

GLY

GLY

GLY

GLY

GLY

ALA

ALA

ALA

ALA

ALA

O ALA N GLN H GLN CA GLN CB GLN CG GLN CD GLN OE1 GLN NE2 GLN 1179 1179 1179 1179 1179 1179 1179 1180 1180 1180 1180 1180 1181 1181 1181 1181 1181 1181 1182 1182 1182 1182 1182 1182 1182 1182 1182 1182 1182 1182 1183 1183 1183 1183 1183 1183 1183 1183 15.087 -29.234 14.933 -31.307 14.183 -31.423 12.801 -31.106 12.751 -30.143 16.303 -31.898 17.190 -31.306 16.475 -33.096 15.843 -33.441 17.719 -33.778 18.692 -33.270 18.351 -32.970 19.879 -33.121 19.932 -33.275 21.082 -32.730 22.129 -32.393 21.143 -31.629 21.590 -31.937 20.762 -30.374 20.272 -30.169 20.962 -29.298 20.064 -29.532 18.601 -29.269 17.692 -29.877 17.243 -29.245 17.413 -31.156 17.810 -31.600 16.769 -31.597 22.417 -29.095 22.746 -28.817 23.336 -29.158 23.097 -29.276 24.738 -28.955 25.517 -29.736 24.892 -29.453 25.621 -29.318 25.531 -31.245 25.053 -27.462 38.985 39.223 37.897 38.019 38.120 39.010 38.393 39.533 40.193 39.337 40.364 41.505 39.810 38.847 40.497 39.454 41.539 42.643 41.309 40.490 42.309 43.545 43.273 44.324 45.289 44.135 43.352 44.723 42.787 43.947 41.837 40.898 42.096 41.010 39.753 39.122 41.285 42.074 1.00 0.00 1.00 28.15 1.00 28.43 1.00 41.75 1.00 0.00 1.00 26.65 1.00 23.06 1.00 24.46 1.00 0.00 1.00 24.52 1.00 26.59 1.00 27.29 1.00 29.30 1.00 0.00 1.00 31.94 1.00 38.26 1.00 33.00 1.00 40.36 1.00 29.27 1.00 0.00 1.00 28.61 1.00 23.51 1.00 29.62 1.00 35.92 1.00 37.09 1.00 45.00 1.00 0.00 1.00 0.00 1.00 23.87 1.00 22.97 1.00 18.65 1.00 0.00 1.00 16.92 1.00 18.51 1.00 17.00 1.00 0.00 1.00 18.60 1.00 14.68 4428 HE21 GLN 4429 HE22 GLN 4430 C GLN 4431 O GLN 4432 N THR 4433 H THR 4434 CA THR 4435 CB THR 4436 OG1 THR 4437 HG1 THR 4438 CG2 THR 4439 C THR 342 ATOM 4440 0 THR 1183 24.370 -26.721 4131 .0 183 41.361 1.00 18.03

ATOM

ATOM

ATOM

a.

a.

a a a a a a a

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

4441 4442 4443 4444 4445 4446 4447 4448 4449 4450 4451 4452 4453 4454 4455 4456 4457 4458 4459 4460 4461 4462 4463 4464 4465 4466 4467 4468 4469 4470 4471 4472 4473 4474 4475 4476 4477 N ASP H ASP CA ASP CB ASP CG ASP ODi ASP 0D2 ASP C ASP 0 ASP N GLY H GLY CA GLY C GLY

GLY

N LYS H LYS CA LYS CE LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS 1184 1184 1184 1184 1184 1184 1184 1184 1184 1185 1185 1185 1285 1155 11S6 1186 1186 1186 1186 1186 1186 1186 1186 1136 113 6 1137 113 7 1:7 1187 1187 1137 1137 1187 1187 26.065 -26.9 61 26.579 -27.569 26.404 -25.549 27.536 -25.242 27.176 -25.188 28.084 -25.277 25.990 -25.054 26.828 -25.115 27.602 -25.817 26.262 -23.997 25.633 -23.519 26.561 -23.443 25.741 -24.063 26.035 -23.832 24.734 -24.889 24.547 -25.122 23.860 -25.398 23.012 -26.505 22.022 -27.129 21.252 -27.977 20.043 -28.626 19.440 -29.535 20.110 -30.295 18.582 -29.942 19.194 -29.024 23.024 -24.186 22.539 -23.457 22.836 -23.931 23.152 -24.577 22.222 -22.688 23.316 -21.609 24.161 -21.823 23.895 -21.065 25.167 -22.802 24.631 -21.297 25.904 -23.023 25.639 -22.275 21.441 -22.811 42.779 43.353 42.741 43 .695 45.170 46.010 45 .471 41. 356 40.695 40.918 41 .496 39.614 38.499 37 .331 38.778 39.711 37 .737 38 .326 37 .379 38.361 37 .721 38.677 38 .908 38.257 39.546 37.303 38.176 36.007 35.337 35.554 35.354 34 .092 32.936 34.076 31.788 32 .918 31.776 1.00 13.66 1.00 0.00 1.00 15.21 1.00 10.46 1.00 12.60 1.00 10.75 1.00 12.16 1.00 16.93 1.00 21.40 1.00 14.05 1.00 0.00 1.00 14.01 1.00 15.04 1.00 13.07 1.00 14.59 1.00 0.00 1.00 14.21 1.00 12.61 1.00 14.10 1.00 22.79 1.00 27.95 1.00 30.90 1.00 0.00 1.00 0.00 1. 00 0.00 1.00 14.69 1.00 12.22 1.00 11.37 1.00 0.00 1.00 11.00 1.00 3 .59 1.00 10.48 1.00 4.12 1.00 4.77 1.00 2.00 1.00 3.39 1.00 2.00

LYS

LYS

PHE

PHE

PHE

PE

CG PHE CD1 PHE CD2 PHE CEl PE CE2 PHE CZ PHE ATOM 4478 C PHE 1137 34.251 1.00 12.70 343 WO 97/08300

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

4479 4480 4481 4482 4483 4484 4485 4486 4487 4488 4489 4490 4491 4492 4493 4494 4495 4496 4497 4498 4499 4500 4501 9 9 9 *99* .9 9 999* 9* 9**9 *9*9 9 9 1-

I-

F.

0 PHE N LEU 1188 H LEU 1188 CA LEU 1188 CB LEU 1188 CG LEU 1188 CD1 LEU 1188 CD2 LEU 1188 C LEU 1188 O LEU 1188 N LEU 1189 H LEU 1189 CA LEU 1189 CB LEU 1189 CG LEU 1189 CDI LEU 1189 CD2 LEU 1189 C LEU 1189 O LEU 1189 N ARG 1190 H ARG 1190 CA ARG 1190 CB ARG 1190 CG ARG 1190 CD ARG 1190 NE ARG 1190 HE ARG 1190 CZ ARG 1190 NH1 ARG 1190 HII ARG 1190 1H12 ARG 1190 NH2 ARG 1190 1H21 ARG 1190 1H22 ARG 1190 C ARG 1190 ARG 1190 N PRO 1191 CD PRO 1191 CA PRO 1191 1187 21.629 -23.757 20.617 -21.805 20.500 -21.083 19.932 -21.659 18.537 -22.312 17.434 -21.857 16.675 -20.662 16.444 -22.984 19.834 -20.148 19.923 -19.356 19.732 -19.698 19.712 -20.341 19.464 -18.312 20.505 -17.760 20.749 -16.264 22.234 -15.989 20.093 -15.606 18.105 -18.311 17.787 -19.243 17.268 -17.316 17.569 -16.616 15.940 -17.192 14.872 -17.742 14.816 -16.996 13.866 -17.619 14.272 -17.195 14.905 -17.754 13.838 -16.071 12.979 -15.236 12.632 -15.428 12.684 -14.419 14.356 -15.731 15.053 -16.316 14.070 -14.895 15.654 -15.715 16.245 -14.815 14.809 -15.374 14.125 -16.305 14.427 -14.014 33.980 34.639 32.705 32.777 33.728 33.151 33.915 32.432 33.384 31.178 30.439 30.886 29.951 29.994 29.946 28.818 30.221 29.481 30.494 31.112 29.930 30.924 32.246 33.244 34.574 35.065 35.155 34.576 33 .659 35.066 36.323 36.734 36.785 29.608 30.226 28.625 27.724 28.335 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 15.30 0.00 13.51 8.23 8.72 6.00 3-.86 17.33 16.73 11.00 0.00 8.88 9.47 11.16 14.98 17 .03 10.34 11.32 11.83 0.00 12 10.80 16 .94 10.51 14 .51 0.00 11.97 8.12 0.00 0.00 8.29 0.00 0 .00 14 .97 15.61 14.74 14.72 15 33.469 1.00 14.29 ATOM 4502 25 ATOM 4503 ATOM 4504 ATOM 4505 ATOM 4506 ATOM 4507 ATOM 4508 ATOM 4509 ATOM 4510 ATOM 4511 ATOM 4512 ATOM 4513 ATOM 4514 ATOM 4515 ATOM 4516 ATOM 4517 344 00 0 0 0

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

4518 4519 4520 4521 4522 4523 4524 4525 4526 4527 4528 4529 4530 4531 CB PRO CG PRO C PRO 0 PRO N ARG H ARG CA ARG CB ARG CG ARG CD ARG NE ARG HE ARG CZ ARG NH1 ARG 4532 HH11 ARG 4533 HH12 ARG 4534 NH2 ARG 4535 HH21 ARG 4536 HH22 ARG 4537 4538 4539 4540 4541 4542 4543 4544 4545 4546 4547 4548 4549 4550 4551 4552 4553 4554 4555 4556

ARG

ARG

LYS

LYS

LYS

LYS

1191 1191 1191 1191 1192 1192 1192 1192 1192 1192 1192 1192 1192 1192 1192 1192 1192 1192 1192 1192 1192 1193 1193 1193 1193 1193 1193 1193 1193 1193 1193 1193 1193 1193 1194 1194 1194 1194 1194 13 .942 -14. 095 13.230 -15.430 13.377 -13.599 12.559 -14.420 13.392 -12.351 14.020 -11.697 12.390 -11.919 12.896 -10.822 14.046 -11.166 14.060 -10.221 14.004 -8.826 14.571 -8.533 13.214 -7.909 12.378 -8.164 12.311 -9.088 11.820 -7.426 13.296 -6.674 13.919 -6.471 12.741 -5.948 11.241 -11.367 11.345 -11.120 10.133 -11.182 10.123 -11.503 8.919 -10.627 7.862 -10.552 8.242 -9.817 7.395 -10.421 7.441 -9.651 6.716 -8.403 5.768 -8.597 7.230 -7.776 6.627 -7.945 9.200 -9.258 8.681 -8.919 10.063 -8.465 10.545 -8.826 10.422 -7.154 11.099 -6.342 10.161 -6.091 26.902 26.849 29.354 29.789 29.787 29.417 30.731 31.655 32.595 33.763 33.365 32.622 33.937 34.943 35.321 35.322 33.467 32.711 33.873 29.915 28.703 30.620 31.549 30.059 31.167 32.469 33.597 34.907 34.764 34.383 34.112 35.693 29.465 28.400 30.107 30.876 29.598 30.699 1.00 20.02 1.00 12.74 1.00 17.84 1.00 18.29 1.00 16.50 1.00 0.00 1.00 19.93 1.00 16.49 1.00 10.36 1.00 10.83 1.00 21.58 1.00 0.00 1.00 17.94 1.00 12.97 1.00 0.00 1.00 0.00 1.00 21.28 1.00 0.00 1.00 0.00 1.00 28.96 1.00 32.17 1.00 35.58 1.00 0.00 1.00 39.90 1.00 44.44 1.00 50.54 1.00 54.35 1.00 50.38 1.00 50.92 1.00 0.00 1.00 0.00 1.00 0.00 1.00 42.01 1.00 45.17 1.00 43.21 1.00 0.00 1.00 42.46 1.00 45.15 CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS o LYS N GLU H GLU CA GLU CB GLU CG GLU 31.888 1.00 51.05 345 ATOM 4557 CD GLU 1194 10.620 -5.135 32.997 1.00 54.40 ATOM 4558 OE1 GLU 1194 11.621 -4.428 32.841 1.00 51.74 ATOM 4559 0E2 GLU 1194 9.960 -5.106 34.040 1.00 53.43 ATOM 4560 C GLU 1194 11.374 -7.449 28.450 1.00 41.34 ATOM 4561 0 GLU 1194 12.396 -8.111 28.620 1.00 41.69 ATOM 4562 N GLN 1195 11.021 -7.015 27.252 1.00 41.74 ATOM 4563 H GLN 1195 10.212 -6.475 27.187 1.00 0.00 ATOM 4564 CA GLN 1195 11.787 -7.317 26.052 1 .0A0 41 .57 ATOM 4565 CB GLN 1195 10.993 -6.804 24.850 1.00 49.15 ATOM 4566 CG GLN 1195 9.692 -7.586 24.621 1.00 57.96 ATOM 4567 CD GLN 1195 9.918 -9.056 24.262 1.00 62.70 ATOM 4568 OE1 GLN 1195 10.451 -9.376 23.198 1.00 67.19 ATOM 4569 NE2 GLN 1195 9.529 -10.002 25.108 1.00 63.28 ATOM 4570 HE21 GLN 1195 9.110 -9.750 25.959 1.00 0.00 15 ATOM 4571 HE2 2 GLN 1195 9.686 -10.930 24.842 1.00 0.00 *ATOM 4572 C GLN 1195 13.201 -6.763 26.036 1.00 36.58 ATOM 4573 0 GLN 1195 13.410 -5.624 26.442 1.00 38.41 ATOM 4574 N GLY 1196 14.180 -7.567 25.631 1.00 33.45 ATOM 4575 H GLY 1196 13.953 -8.505 25.441 1.00 0.00 20 ATOM 4576 CA GLY 1196 15.579 -7.149 25.576 1.00 27.92 ATOM 4577 c GLY 1196 16.373 -7.473 26.850 1.00 20.50 ATOM 4578 0 GLY 1196 17.596 -7.331 26.896 1.00 17.86 ATOM 4579 N THR 1197 15.713 -7.930 27.912 1.00 21.77 ATOM 4580 H THR 1197 14.758 -8.129 27.852 1.00 0.00 ATOM 4581 CA THR 1197 16.376 -8.267 29.151 1.00 15.76 ATOM 4582 CB TER 1197 15.701 -7.539 30.329 1.00 16.54 ATOM 4583 001 THR 1197 14.355 -7.984 30.455 1.00 18.76 ATOM 4584 HG1 THR 1197 13.876 -7.758 29.653 1.00 0.00 ATOM 4585 CG2 THR 1197 15.758 -6.037 30.127 1.00 15.13 ATOM 4586 c THR 1197 16.300 -9.769 29.328 1.00 16.59 ATOM 4587 0 THP. 1197 15.438 -10.452 28.738 1.00 17.00 ATOM 4588 N TYR 1198 17.204 -10.298 30.140 1.00 14.48 ATOM 4589 H TYR 1198 17.739 -9.719 30.720 1.00 0.00 ATOM 4590 CA TYR 1198 17.356 -11.719 30.325 1.00 16.70 ATOM 4591 CB TYR 1198 18.556 -12.201 29.519 1.00 17.59 ATOM 4592 CG TYR 1198 18.374 -12.049 28.008 1.00 21.32 ATOM 4593 CD1 TYR 1198 18.820 -10.906 27.326 1.00 16.75 ATOM 4594 CEl TYR 1198 18.609 -10.791 25.950 1.00 19.88 ATOM 4595 CD2 TYR 1198 17.725 -13.072 27.304 1.00 25.15 346 ATOM 4596 CE2 TYR 1198 17.509 -12.964 25.929 1.0O0 25.33

ATOM

ATOM

ATOM

ATOM

ATOM

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1 5 ATOM

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20 ATOM

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ATOM

ATOM

ATOM

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ATOM

ATOM

ATOM

4597 4598 4599 4600 4601 4602 4603 4604 4605 4606 4607 4608 4609 4610 4611 4612 4613 4614 4615 4616 4617 4618 4619 4620 4621 4622 4623 4624 4625 4626 4627 4628 4629 4630 4631 4632 4633 4634 CZ TYR 1198 OH TYR 1198 HH TYR 1198 C TYR 1198 O TYR 1198 N ALA 1199 H ALA 1199 CA ALA 1199 CB ALA 1199 C ALA 1199 O ALA 1199 N LEU 1200 H LEU 1200 CA LEU 1200 CB LEU 1200 CG LEU 1200 CD1 LEU 1200 CD2 LEU 1200 C LEU 1200 O LEU 1200 N SER 1201 H SER 1201 CA SER 1201 CB SER 1221 OG SER 2:Z1 HG SER 1:-i C SER 1201 O SER 1201 N LEU 1202 H LEU 1202 CA LEU 1202 CB LEU 1202 CG LEU 1202 CDI LEU 1202 CD2 LEU 1202 C LEU 1202 O LEU 1202 N ILE 1203 17.954 -11.824 17.748 -11.741 17.993 -10.861 17.589 -11.975 18.007 -11.074 17.351 -13.168 17.003 -13.882 17.694 -13.466 16.446 -13.646 18.501 -14.755 18.152 -15.740 19.653 -14.684 19.907 -13.807 20.499 -15.823 21.895 -15.345 23.093 -15.967 24.235 -15.618 22.921 -17.455 19.975 -16.527 19.911 -15.893 19.539 -17.787 19.637 -18.340 19.073 -18.416 17.702 -18.992 16.765 -17.981 17.018 -17.717 20.091 -19.498 20.425 -20.250 20.600 -19.589 20.254 -19.000 21.622 -20.553 23.010 -19.859 23.690 -19.359 25.112 -19.872 23.778 -17.875 21.341 -21.242 20.596 -20.712 21.873 -22.422 25.263 23.894 23.598 31.791 32.512 32.283 31.710 33.659 34.500 33.690 33.036 34.355 34.720 34.655 34.915 34.261 35.215 33.940 35.934 37.002 35.929 35.125 37.154 36 .893 36.540 35.640 37.493 36 .565 38.739 39.443 39.113 39.184 40.485 40.531 40.526 40.449 41.265 40.728 00 26.49 1.00 36.63 1.00 0.00 !.00 14.67 .00 18.92 00 12.49 1.00 0.00 !.00 10.60 1.00 3.99 1.00 9.64 1.00 11.40 1.00 6.80 DO0 0.00 .0 9.47 1.00 8.55 1.00 12.62 1.00 4.18 1.00 2.53 !.00 10.31 i.00 9.18 00 8.80 1.00 0.00 i.00 10.37 00 11.67 1.0 13.11 i. 00 0.00 i.00 13.77 00 13.42 00 10.94 !.00 0.00 00 10.67 1.00 16.39 i.00 15.58 00 18.14 00 14.38 1 00 11.37 1.00 13.60 1.00 13.31 347 ATOM 4635 H ILE 1203 22.435 -22.841 4.4 .0 00 40.047 1.00 0.00 ATOM 4636 ATOM 4637 ATOM 4638 ATOM 4639 ATOM 4640 ATOM 4641 ATOM 4642 ATOM 4643 ATOM 4644 ATOM 4645 ATOM 4646 ATOM 4647 ATOM 4648 1 5 ATOM 4649 ATOM 4650 ATOM 4651 ATOM 4652 ATOM 4653 20 ATOM 4654 ATOM 4655 ATOM 4656 ATOM 4657 ATOM 4658 ATOM 4659 ATOM 4660 ATOM 4661 ATOM 4662 ATOM 4663 ATOM 4664 ATOM 4665 ATOM 4666 ATOM 4667 ATOM 4668 ATOM 4669 ATOM 4670 ATOM 4671 ATOM 4672 ATOM 4673 CA ILE CB ILE CG2 ILE CG1 ILE CD ILE C ILE O ILE N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CEI TYR CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR C TYR O TYR N GLY H GLY CA GLY C GLY O GLY N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS 1203 1203 1203 1203 1203 1203 1203 1204 1204 1204 1204 1204 1204 1204 1204 1204 1204 1204 1204 1204 1204 1205 1205 1205 1205 1205 1206 1206 1206 1206 1206 1206 1206 1206 1206 1206 1206 1206 21.704 -23.099 21.585 -24.650 22.002 -25.404 20.156 -25.035 19.137 -25.145 22.939 -22.781 24.056 -22.800 22.777 -22.459 21.887 -22.190 23.881 -22.380 24.481 -20.973 25.533 -20.915 26.792 -21.469 27.736 -21.503 25.219 -20.383 26.162 -20.425 27.407 -20.991 28.302 -21.141 29.180 -20.904 23.203 -22.728 22.156 -22.157 23.708 -23.725 24.387 -24.311 23.143 -24.100 21.709 -24.580 20.825 -24.345 21.503 -25.225 22.286 -25.417 20.208 -25.701 19.836 -26.968 20.929 -28.011 20.424 -29.318 21.540 -30.357 20.937 -31.658 20.351 -31.871 20.337 -31.657 21.669 -32.389 19.114 -24.648 41. 999 41. 781 43 .049 41. 396 42 .573 42.819 42.305 44.090 44.403 45.021 45.109 46.211 45.978 47 .007 47.473 48 .499 48.257 49.285 48.957 46.322 46.640 47.057 46.661 48.356 48.227 49.072 47.068 46.504 46 .603 47.357 47.201 47.766 47.758 47.933 47.101 48.783 48.030 46.728 1.00 11.49 1.00 18.26 1.00 15.92 1.00 20.04 1.00 21.80 1.00 7.80 1.00 10.96 1.00 10.54 1.00 0.00 1.00 6.13 1.00 10.48 1.00 7.51 1.00 2.91 1.00 6.56 1.00 6.54 1.00 4.63 1.00 5.40 1.00 6.25 1.00 0.00 1.00 8.98 1.00 9.89 1.00 10.19 1.00 0.00 1.00 5.00 1.00 9.1i9 1.00 10.18 1.00 8.86 1.00 0.00 1.00 4 .66 1.00 6.05 1.00 4.25 1.00 10.92 1.00 10.58 1.00 19.07 1.00 0.00 1.00 0.00 1.00 0.00 1.00 4.89 348 ATOM 4674 0 LYS 1206 17.957 -24.880 4.9 .0 72 47.090 1.00 7.21 9

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4675 4676 4677 4678 4679 4680 4681 4682 4683 4684 4685 4686 4687 4688 4689 4690 4691 4692 4693 4694 4695 4696 4697 4698 4699 4700 4701 4702 4703 4704 4705 4706 4707 4708 4709 4710 4711 4712 N TH.

H THR CA THR CB THR OGi THR HG1 THR CG2 THR C THR O THR N VAL H VAL CA VAL CB VAL CG1 VAL CG2 VAL C VAL 0 VAL N TYR H TYR CA TYR CB TYR CG TYR CD1 TYR CE1 TYR CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR C TYR 0 TYR N HIS H HIS CA HIS CB HIS CG HIS CD2 HIS ND1 HIS 1207 1207 1207 1207 1207 1207 1207 1207 1207 1208 1208 1208 1208 1208 1208 1208 1208 1209 1209 1209 1209 1209 1209 1209 1209 1209 1209 1209 1209 1209 1209 1210 1210 1210 1210 1210 1210 1210 19.538 -23.433 20.471 -23.265 18.654 -22.282 18.993 -21.309 19.044 -22.042 19.657 -22.792 17.935 -20.225 18.933 -21.646 20.094 -21.520 17.897 -21.317 16.986 -21.474 18.092 -20.657 16.848 -20.878 17.103 -20.322 16.583 -22.363 18.313 -19.169 17.641 -18.561 19.289 -18.559 19.866 -19.105 19.543 -17.127 21.023 -16.904 21.281 -17.214 21.096 -16.209 21.199 -16.504 21.591 -18.512 21.691 -18.807 21.492 -17.805 21.555 -18.089 21.525 -19.044 19.176 -16.557 19.307 -17.306 18.677 -15.326 18.622 -14.715 18.366 -14.805 16.886 -14.536 16.007 -15.770 15.433 -16.228 15.657 -16.621 46.388 46.151 46.327 47.469 48.695 48.654 47.600 44.964 44.566 44.203 44.529 42.924 42 .006 40.612 41.833 43 .185 44.021 42.538 41.961 42 .598 42 .917 44 .376 45.327 46.682 44.783 46.138 47.080 48 .425 48.552 41.227 40.258 41.036 41.807 39.699 39.478 39.564 40.731 38.613 1.00 8.77 1.00 0.00 1.00 11.18 1.00 8.66 1.00 18.34 1.00 0.00 1.00 2.00 1.00 8.75 1.00 11. 11 1.00 11.99 1.00 0.00 1.00 11.25 1.00 13.46 1.00 10.87 1.00 8.09 1.00 9.93 1.00 12.68 1.00 10.99 1.00 0.00 1.00 9.13 1.00 7.91 1.00 13.41 1.00 16.92 1.00 22.64 1.00 13.00 1.00 14.79 1.00 18.04 1.00 16.55 1.00 0.00 1.00 9.15 1.00 9.61 1.00 9.91 1.00 0.00 1.00 7.08 1.00 9.03 1.00 8.44 1.00 10.80 1.00 11.46 349 ATOM 4713 HD1 HIS 1210 15.996 -16.657 3.8 .0 00 37.689 1.00 0.00

S

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1 5 ATOM

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4714 4715 4716 4717 4718 4719 4720 4721 4722 4723 4724 4725 4726 4727 4728 4729 4730 4731 4732 4733 4734 4735 4736 4737 4738 4739 4740 4741 4742 4743 4744 4745 4746 4747 4748 4749 4750 CEl NE2 HE2

C

0

N

H

CA

CB

CG

CD1 CEl CD2 CE2 Cz

OH

HH

C

0

N

H

CA

CB

CG

CD1 CD2

C

0

N

H

CA

CB

CG2 CGl

CD

C

0 HIS 1210 HIS 1210 HIS 1210 HIS 1210 HIS 1210 TYR 1211 TYR 1211 TYR 1211 TYR 1211 TYR 1211 TYR 1211 TYR 1211 TYR 1211 TYR 1211 TYR 1211 TYR 1211 TYR 1211 TYR 1211 TYR 1211 LEU 1212 LEU 1212 LEU 1212 LEU 1212 LEU 1212 LEU 1212 LEU 1212 LEU 1212 LEU 1212 ILE 1213 ILE 1213 ILE 1213 ILE 1213 ILE 1213 ILE 1213 ILE 1213 ILE 1213 ILE 1213 14.908 -17.563 14.785 -17.314 14.360 -17.908 19.057 -13.487 18.956 -12.579 19.794 -13.329 19.870 -14.074 20.501 -12.089 21.990 -12.387 22.642 -12.837 22.545 -14.176 23.138 -14.579 23.333 -11.897 23.928 -12.305 23.829 -13.642 24.419 -14.055 24.763 -13.294 19.940 -11.461 19.623 -12.200 19.779 -10.150 20.110 -9.570 19.216 -9.514 18.486 -8.205 17.893 -7.281 16.934 -8.055 17.122 -6.164 20.350 -9.193 21.414 -8.791 20.155 -9.402 19.286 -9.744 21.132 -9.052 21.647 -10.301 22.612 -9.851 22.333 -11.271 22.178 -12.708 20.300 -8.185 19.143 -8.504 20.850 -7.068 39.136 40.416 41. 068 39.455 40.269 38.372 37.737 38.069 37.885 39.175 39.587 40.782 39.950 41.144 41.549 42.720 43.222 36.795 35.866 36.679 37.399 35.488 35.850 34.785 33 .937 35.416 34.556 35. 005 33.274 32.985 32.258 31.495 30.394 32.457 31.951 31.319 31.032 30.870 1.00 7.08 1.00 10.12 1.00 0.00 1.00 9.93 1.00 8.85 1.00 10.56 1L.00 0.00 1.00 14.64 1.00 8.91 1.00 13.49 1.00 11.64 1.00 8.95 1.00 10.65 1.00 8.87 1.00 11.65 1.00 10.12 1.00 0.00 1.00 12.65 1.00 15.74 1.00 14.20 1.00 0.00 1.00 13.88 1.00 17.25 1.00 11.92 1.00 15.10 1.00 16.39 1.00 11.08 1.00 15.63 1.00 11.41 1.00 0.00 1.00 11.27 1.00 10.65 1.00 2.00 1.00 8.10 1.00 6.60 1.00 12.26 1.00 11.97 1.00 15.76 ATOM 4751 N SER 1214 350 ATOM 4752 H SER 1214 ATM 72 SR124 21.733 -6.808 31.218 1.00 0.00

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1 5 ATOM 4753 4754 4755 4756 4757 4758 4759 4760 4761 4762 4763 4764 4765 4766 CA SER 1214 CB SER OG SER HG SER C SER O SER N GLN H GLN CA GLN CB GLN CG GLN CD GLN OE1 GLN NE2 GLN ATOM 4767 HE21 GLN ATOM 4768 HE22 GLN ATOM 4769 C GLN ATOM 4770 0 GLN ATOM 4771 N ASP ATOM 4772 H ASP ATOM 4773 CA ASP ATOM 4774 CB ASP ATOM 4775 CG ASP ATOM 4776 ODi ASP ATOM 4777 0D2 ASP ATOM 4778 C ASP ATOM 4779 0 ASP ATOM 4780 N LYS ATOM 4781 H LYS ATOM 4782 CA LYS ATOM 4783 CB LYS ATOM 4784 CG LYS ATOM 4785 CD LYS ATOM 4786 CE LYS ATOM 4787 NZ LYS ATOM 4788 HZ1 LYS ATOM 4789 HZ2 LYS ATOM 4790 HZ3 LYS 1214 1214 1214 1214 1214 1215 1215 1215 1215 1215 1215 1215 1215 1215 1215 1215 1216 1216 1216 1216 1216 1216 12:-6 1216 1216 12 17- 1217 1217 1217 1217 1217 1217 1217 1217 1217 1217 20.219 19.346 19.967 20.764 21.344 22.539 21.012 20.071 22 .007 21.641 21.706 21.354 20.229 22.322 23.233 22.094 22.069 21.025 23.268 24.038 23.475 24.925 26.085 25.889 27.226 23.211 23 .013 23.334 23.459 23.128 23.521 24.974 25.357 26.753 27.053 26.961 26.396 28.028 -6.188 -5.168 -4.636 -4 .188 -5.515 -5.704 -4.789 -4.719 -4 .049 -3.996 -5.377 -5.525 -5.858 -5.400 -5.230 -5.496 -2.625 -2.008 -2.124 -2.731 -0.736 -0.587 -0.812 -0.887 -0.886 0.206 -0.268 1.527 1.868 2 .473 3 .892 4.178 3.646 4.133 3.846 2.826 4.369 4.149 29.898 30.653 31. 807 31.502 29.112 29.420 28.040 27.781 27.261 25.761 25.155 23.684 23 .301 22.793 23.113 21.847 27.789 28.024 28.048 28.000 28.451 28.951 27.960 26.747 28.401 27.275 26.157 27.414 28.323 26.302 26.747 27.188 28.595 28.992 30.383 30.561 31. 000 30.584 1.00 11.43 1.00 8.83 1.00 13.26 1.00 0.00 1.00 12.87 1.00 9.60 1.00 13.37 1. 00 0.00 1.00 16.58 1.00 15.14 1.00 19.92 1.00 23.57 00 25.08 1. C0 24.06 1.00 0.00 1.00 0.00 1.00 16.06 1.00 19.32 1.00 17.64 1.00 0.00 1.00 21.35 1.00 20.33 1.00 18.82 1.00 18 .33 1.00 15.08 1.00 22.60 1.00 24.68 1.00 27.26 1.00 0.00 1.00 26.76 1.00 28.33 1.00 40.57 1.00 49.59 1.00 51.93 1.00 52.30 1.00 0.00 1.00 0.00 1.00 0.00 351 ATOM 4791 C LYS 1217 ATM 79 C LY 117 23.856 2.171 24.973 1.00 23.75

S

*5

S.*

S

55.55.

S

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1 5 ATOM

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20 ATOM

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4792 4793 4794 4795 4796 4797 A O 4799 4800 4801 4802 4803 4804 4805 4806 4807 4808 4809 4810 4811 4812 4813 4814 4815 4816 4817 4818 4819 4820 4821 4822 4823 4824 4825 4826 4827 4828 4829 0 LYS N ALA H ALA CA ALA CB ALA C ALA O r AL N GLY H GLY CA GLY C GLY O GLY N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS o LYS N TYR H TYR C A TYR CB TYR CG TYR CD1 TYR CEl TYR CD2 TYR CE2 TYR C Z TYR OH TYR HH TYR C TYR 1217 1218 1218 1218 1218 1218 -~119 1219 1219 1219 1219 1219 1220 1220 1220 1220 1220 1220 1220 1220 1220 1220 1220 1220 1220 1221 1221 1221 1221 1221 1221 1221 1221 1221 1221 1221 1221 23.414 24.992 25.278 25.789 27.250 25.574 26.304 24.611 23.937 24.399 25.163 24.891 26.090 26.312 26.804 28.063 29.005 30.498 30.945 32.384 32.708 32.874 32.599 25.940 25.205 25.990 26.544 25.273 25.187 24.259 24.784 23 .964 22.902 22.075 22.612 21. 836 21.836 25.965 2 .526 1 .488 1.175 1 .160 1.338 -0 .245 -1 .018 -0 .541 -2 .368 -3 .491 -4 .659 -3 .212 -2 .276 -4 .244 -3 669 -3 .055 -3.312 -4 .758 -4 .971 -4 .762 -4 .347 -5 .961 -4 .884 -4 .205 -6 .217 -6 .646 -7 069 -8 .490 -8 .599 -8 .501 -8 .672 -8 .856 -9.031 -8 .950 -9 .245 -8.487 -7 .106 23.881 25.066 25.942 23.913 24.283 23.355 22.447 23.852 24.458 23.337 24.043 23.791 24.938 25 .072 25.668 26.313 25.284 25.537 25.267 25.363 26.328 24.690 25.132 26.745 27 .477 26.744 26.066 27.673 27.087 25.884 24.600 23.486 26.051 24.930 23 .645 22.524 21. 914 29.035 1.00 22.76 1.00 19.56 1.00 0.00 1.00 18.97 1.00 12.65 1.00 20.40 1.0 A 1.00 17.93 1.00 0.00 1.00 18.40 1.00 12.63 1.00 14.94 1.00 9.76 1.00 0.00 1.00 12.80 1.00 11.80 1.00 13.40 1.00 31.03 1.00 36.30 1.00 35.49 1.00 0.00 1.00 0.00 1.00 0.00 1.00 14.51 1.00 15.43 1.00 12.28 1.00 0.00 1.00 10.89 1.00 7.55 1.00 6.89 1.00 5 .33 1.00 11.81 1.00 10.91 1.00 9 .53 1.00 12.73 1.00 13.45 1.00 0.00 1.00 9.20 352

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ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

4830 4831 4832 4833 4834 4835 4836 4837 4838 4839 4840 4841 4842 4843 4844 4845 4846 4847 4848 4849 4850 4851 4852 4853 4854 4855 4856 4857 4858 4859 4860 4861 4862 4863 4864 4865 4866 4867 4868 0 TYR N CYS H CYS CA CYS CB CYS SG CYS C CYS 0 CYS N ILE H ILE CA ILE CB ILE CG2 ILE CGl ILE CD ILE C ILE O ILE N PRO CD PRO CA PRO CB PRO CG PRO C PRO O PRO N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU O GLU N GLY H GLY CA GLY C GLY o GLY 1221 1222 1222 1222 1222 1222 1222 1222 1223 1223 1223 1223 1223 1223 1223 1223 1223 1224 1224 1224 1224 1224 1224 1224 1225 1225 1225 1225 1225 1225 1225 1225 1225 1225 1226 1226 1226 1226 1226 27.197 25.234 24.293 25.842 26. 711 25. 843 24.800 23.617 25.180 26.097 24.318 24.724 24 .025 -7.211 -6.957 -6.678 -7 .089 878 -4.300 -7.225 -6.955 -7.769 -8.112 -7.763 -8.944 -8.884 24.377 -10.221 25.066 -11.480 24.614 25.728 23.748 22.306 24.084 22.861 21.742 25.385 25.603 26.275 26.005 27.633 27.681 26.836 27.086 28.228 26.122 28.603 29.715 28.247 27.411 29.065 29 .877 29.805 -6.396 -5.880 -5.694 -5.965 -4.405 -4.093 -4 .611 -4.433 -5.267 -3.545 -2.981 -3.336 -3.285 -2.196 -0.782 -0.304 -0.169 -4.402 -4.474 -5.202 -5.024 -6.317 -6.033 -4.940 29.109 3 0.127 30. 068 31.435 31. 730 31. 769 32.519 32.302 33.671 33.760 34. 866 35.792 37.166 35.054 35.556 35.509 35.285 36.263 36.414 36.834 37.629 36.743 37.614 38.490 37 .179 36.426 37.680 39.233 39.917 39.391 39.447 38.917 37.208 37.705 36.203 35.728 35.745 34.498 1.00 13.58 1.00 8.73 1.00 0.00 1.00 11.15 1.00 13.63 1.00 15.70 1.00 9.43 1.00 13.63 1.00 13.65 1.00 0.00 1.00 11.24 1.00 12.90 1.00 8.32 1.00 12.18 1.00 14.74 1.00 10.19 1.00 9.63 1.00 11.43 1.00 7.97 1.00 7.55 1.00 9.42 1.00 3.67 1.00 14.05 1.00 18.66 1.00 13 .58 1.00 0.00 1.00 14.68 1.00 17.95 1.00 24.12 1.00 31.41 1.00 30.20 1.00 36.60 1.00 12.36 1.00 10.48 1.00 15.65 1.00 0.00 1.00 16.29 1.00 14.66 33.920 1.00 13.35 353

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

4869 4870 4871 4872 4873 4874 4875 4876 4877 4878 4879 4880 4881 4882 4883 4884 4885 4886 4887 4888 4889 4890 4891 4892 4893 4894 4895 4896 4897 4898 4899 4900 4901 4902 4903 4904 4905 4906 4907 N THR H THR CA THR CB THR OGi THR HG1 THR CG2 THR C THR 0 THR N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS 0 LYS N PHE H PHE CA PHE CR PHE CG PHE CD1 PHE CD2 PHE CEl PHE CZE2 PHE CZ PHE C PHE O PHE N ASP H ASP CA ASP CB ASP CG ASP 1227 1227 1227 1227 1227 1227 1227 1227 1227 1228 1228 1228 1228 1228 1228 1228 1228 1228 1228 1228 1228 1228 1229 1229 1229 1229 1229 1229 1229 1229 1229 1229 1229 1229 1230 1230 1230 1230 1230 30.726 30.795 31. 568 32.377 33 .033 33 .642 33 .443 30.659 29.553 31.095 32.012 30.345 30.720 30.633 29.203 29.100 27.704 27.340 27.171 27.599 30.707 31.897 29 .740 28.806 29.996 29 .483 -7.018 -7.807 -6.988 -8.293 -8.487 -9.231 -8.243 -6 .839 -7.372 -6.072 -5.718 -5.772 -4 .416 -3.200 -2.969 -1.660 -1.421 -2.244 -1.309 -0.564 -6.795 -7 .072 -7.331 -7.093 -8.334 -9.753 34.159 34. 735 32.958 32. 879 34. 126 34. 046 31. 825 31. 749 31. 758 30.768 30. 808 29.551 28.983 29. 882 30.270 31.047 31. 359 31. 880 30.473 31.940 28. 493 28. 329 27.756 27. 938 26.722 27.086 28.450 29.599 28.546 30.841 29.794 30.936 25.467 25.535 24. 316 24. 322 23.062 21. 875 21. 591 1.00 15.24 1.00 0.00 1.00 10.28 1.00 9.42 1.00 13.78 1.00 0.00 1.00 4.54 1.00 3.83 1.00 5.42 1.00 9.81 1.00 0.00 1.00 11.73 1.00 11.23 1.00 10.19 1.00 15.20 1.00 14.54 1.00 16.02 1.00 0.00 1.00 0.00 1.00 0.00 1.00 8.65 1.00 8.25 1.00 7.57 1.00 0.00 1.00 11.09 1.00 6.70 1.00 7 .81 1.00 4.30 1.00 5.18 1.00 4.39 1.00 2.00 1.00 2.00 1.00 9.05 1.00 6.36 1.00 11.64 1.00 0.00 1.00 10 .17 1.00 13.12 1.00 12.53

V

V

29.986 -10.207 29.251 -9.901 31.184 -10.912 29.723 -10.303 31.642 -11.307 30.916 -11.005 29.243 -7.961 28.174 -7.361 29.752 -8.369 30.616 -8.832 29.041 -8.183 29.961 -8.319 30.845 -7.122 354 ATOM 4908 ATOM 4909 ATOM 4910 ATOM 4911 ATOM 4912 ATOM 4913 ATOM 4914 ATOM 4915 ATOM 4916 ATOM 4917 ATOM 4918 ATOM 4919 ATOM 4920 ATOM 4921 1 5 ATOM 4922 ATOM 4923 OD1 ASP OD2 ASP C ASP

ASP

THR

THR

THR

C

C

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

4924 4925 4926 4927 4928 4929 4930 4931 4932 4933 4934 4935 4936 4937 CB THR OGI THR HG1 THR CG2 THR C THR O THR N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N TRP H TRP CA TRP CB TRP CG TRP CD2 TRP CE2 TRP CE3 TRP CD1 TRP NEI TRP HE1 TRP CZ2 TRP CZ3 TRP CH2 TRP C TRP 0 TRP N GLN 1230 1230 1230 1230 1231 1231 1231 1231 1231 1231 1231 1231 1231 1232 1.-2 1232 1232 1232 1232 1232 1232 1232 1233 1233 12 3 !23 1223 1233 1233 1233 1233 1233 1233 1233 1233 1233 1233 1233 1234 30.818 -6.121 31.566 -7.190 27.944 -9.184 26.995 -8.933 28.020 -10.298 28.644 -10.378 27.133 -11.398 27.987 -12.342 27.951 -11.835 28.848 -11.875 27.455 -13.705 26.663 -12.002 27.349 -11.890 25.496 -12.649 24.892 -12.549 25.040 -13.393 23.588 -13.738 22.651 -12.624 21.261 -13.177 22.852 -12.135 25.815 -14.682 26.187 -15.071 26.123 -15.312 25.729 -14.988 26.953 -16.503 27.308 -16.919 27.978 -18.285 29.323 -18.581 29.292 -19.979 30.547 -17.921 27.191 -19.400 28.021 -20.410 27.741 -21.338 30.463 -20.727 31.728 -18.659 31.685 -20.056 28.248 -16.248 28.604 -16.992 28.927 -15.161 22.303 20.610 22.853 22.121 23.534 24.281 23.265 22.365 21.031 20.682 22.237 24.573 25.595 24.574 23.803 25.742 25.630 25.993 25.824 27.444 25.902 27.019 24.760 23 .927 24.740 23.298 23.197 23.221 23.111 23.315 23.080 23.028 22.871 23.097 23.305 23.196 25.501 26.411 25.118 18.42 1.00 16.16 1.00 4.73 1.00 10.59 1.00 4.42 1.00 0.00 1.00 8.22 1.00 10.46 1.00 16.76 1.00 0.00 1.00 19.25 1.00 7.92 !.00 12.71 1.00 9.70 i.00 0.00 1.00 11.19 1.00 6.17 S.00 7.65 1.00 10.36 1.00 6.21 1.00 11.62 1.00 11.82 1.00 9.01 1.00 0.00 i.00 7.78 1.00 6.14 1.00 2.05 1.00 2.00 1.00 2.00 1.00 2.00 ATOM 4938 ATOM 4939 ATOM 4940 ATOM 4941 ATOM 4942 ATOM 4943 ATOM 4944 ATOM 4945 ATOM 4946 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1.00 2.03 6.75 0.00 2 .00 5.65 8.83 6.51 8.36 6.74 355 ATOM 4947 H GLN 1234 C C

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

4948 CA GLN 1234 4949 CB GLN 1234 4950 CG GLN 1234 4951 CD GLN 1234 4952 OE1 GLN 1234 4953 NE2 GLN 1234 4954 HE21 GLN 1234 4955 HE22 GLN 1234 4956 C GLN 1234 4957 0 GLN 1234 4958 N LEU 1235 4959 H LEU 1235 4960 CA LEU 1235 4961 CB LEU 1235 4962 CG LEU 1235 4963 CD1 LEU 1235 4964 CD2 LEU 1235 4965 C LEU 1235 4966 0 LEU 1235 4967 N VAL 1236 4968 H VAL 1236 4969 CA VAL 1236 4970 CB VAL 1236 4971 CG1 VAL 1236 4972 CG2 VAL 1236 4973 C VAL 1236 4974 0 VAL 1236 4975 N GLU 1237 4976 H GLU 1237 4977 CA GLU 1237 4978 CE GLU 1237 4979 CG GLU 1237 4980 CD GLU 1237 4981 OE1 GLU 1237 4982 OE2 GLU 1237 4983 C GLU 1237 4984 0 GLU 1237 4985 N TYR 1238 28.578 -14.655 30.182 -14.723 30.769 -13.507 31.525 -13.836 31.929 -12.648 31.120 -11.778 33.160 -12.557 33.803 -13.271 33.377 -11.805 30.026 -14.340 30.995 -14.494 28.850 -13.859 28.120 -13.713 28.597 -13.569 27.231 -12.857 26.722 -12.482 25.924 -11.192 25.848 -13.594 28.625 -14.879 29.360 -14.988 27.889 -15.910 27.318 -15.788 27.901 -17.188 26.875 -18.083 27.052 -19.548 25.526 -17.624 29.293 -17.815 29.800 -18.173 29.966 -17.869 29.542 -17.501 31.285 -18.450 31.731 -18.299 32.556 -19.469 31.960 -20.854 32.730 -21.731 30.754 -21.067 32.303 -17.857 33.099 -18.560 32.261 -16.545 25.713 24.949 23.664 22.780 22.460 22.297 22.504 21.722 27.182 27.937 27.606 26.974 28.994 29.140 30.569 30.485 31.163 29.772 30.753 29.353 28.566 30.044 29.370 29.745 29.837 30.042 31.112 28.888 28.083 28.794 27.366 26.872 27.108 27.468 26.960 29.750 30.379 29.937 1.00 6.24 1.00 6.13 1.00 7.76 1.00 12.06 1.00 11.95 1.00 8.30 1.00 0.00 1.00 0.00 1.00 5.31 1.00 7.22 1.00 4.55 1.00 0.00 1.00 8.63 1.00 9.71 1.00 7.20 1.00 2.31 1.00 6.19 1.00 9.27 1.00 10.18 1.00 12.76 1.00 0.00 1.00 11.18 1.00 6.81 1.00 4.71 1.00 2.30 1.00 12.29 1.00 16.48 1.00 7.45 1.00 0.00 1.00 5.69 1.00 12.37 1.00 21.76 1.00 21.61 1.00 29.48 1.00 24.95 1.00 9.53 1.00 8.53 1.00 11.77 24.365 1.00 0.30

CC

C

CC..

356 ATOM 4986 H TYR 1238 31.610 -16.008 29.438 1.00 0.00

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

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15 ATOM

ATOM

ATOM

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ATOM

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ATOM

4987 4988 4989 4990 4991 4992 4993 4994 4995 4996 4997 4998 4999 5000 5001 5002 5003 5004 5005 5006 5007 5008 5009 5010 5011 5012 5013 5014 5015 5016 5017 5018 5019 5020 5021 5022 5023 5024 CA TYR CB TYR CG TYR CD1 TYR CE1 TYR CD2 TYR CE2 TYR CZ TYR OH TYR HH TYR C TYR O TYR N LEU H LEU CA LEU CB LEU CG LEU CD1 LEU CD2 LEU C LEU O LEU N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS O LYS N LEU H LEU CA LEU CB LEU 1238 1238 1238 1238 1238 1238 1238 1238 1238 1238 1238 1238 1239 1239 1239 1239 1239 1239 1239 1239 1239 1240 1240 1240 1240 1240 1240 1240 1240 1240 1240 1240 1240 1240 1241 1241 1241 1241 33.181 -15.884 33.102 -14.389 34.083 -13.475 35.341 -13.231 36.222 -12.369 33.714 -12.862 34.589 -12.001 35.840 -11.757 36.698 -10.874 37.612 -11.155 32.828 -16.208 33.719 -16.478 31.544 -16.300 30.845 -16.189 31.164 -16.540 29.747 -16.092 29.391 -14.668 27.892 -14.500 30.230 -13.709 31.285 -17.990 31.016 -18.368 31.625 -18.847 31.561 -18.558 31.970 -20.225 31.917 -21.088 30.545 -21.458 30.731 -22.176 29.404 -22.644 29.581 -23.179 30.253 -23.972 29.957 -22.435 28.667 -23.511 33.399 -20.241 33.787 -21.138 34.217 -19.259 33.862 -18.519 35.600 -19.248 36.457 -18.634 30.855 30.537 31.255 30.706 31.370 32.460 33.122 32.571 33.204 33.062 32.320 33.140 32.689 32.007 34.075 34.317 33.989 34.192 34.820 34.484 35.620 33.532 32.596 33.816 32.558 32.032 30.691 30.101 28.763 28.793 28.144 28.392 34.343 35.094 33.962 33.428 34.355 33.282 1.00 12.69 1.00 11.45 1.00 10.47 1.00 9.86 1.00 13.93 1.00 8.70 1.00 7.89 1.00 11.90 1.00 16.71 1.00 0.00 1.00 11.56 1.00 13.31 1.00 10.97 1.00 0.00 1.00 7.36 1.00 5.23 1.00 9.04 1.00 7.48 1.00 9.75 1.00 6.04 1.00 9.78 1.00 10.64 1.00 0.00 1.00 9.28 1.00 3.87 1.00 4.02 1.00 8.38 1.00 11.25 1.00 17.56 1.00 0.00 1.00 0.00 1.00 0.00 1.00 14.71 1.00 21.55 1.00 13.94 1.00 0.00 1.00 14.58 1.00 22.23

S

357 ATOM 5025 CG LEU 1241

S

*5 S

ATOM

ATOM

ATOM

ATOM

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ATOM

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1 5 ATOM

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5026 CD1 LEU 1241 5027 CD2 LEU 1241 5028 C LEU 1241 5029 0 LEU 1241 5030 N LYS 1242 5031 H LYS 1242 5032 CA LYS 1242 5033 CB LYS 1242 5034 CG LYS 1242 5035 CD LYS 1242 5036 CE LYS 1242 5037 NZ LYS 1242 5038 HZ1 LYS 1242 5039 HZ2 LYS 1242 5040 HZ3 LYS 1242 5041 C LYS 1242 5042 0 LYS 1242 5043 N ALA 1243 5044 H ALA 1243 5045 CA ALA 1243 5046 CB ALA 1243 5047 c ALA 1243 5048 o ALA 1243 5049 N ASP 1244 5050 H ASP 1244 5051 CA ASP 1244 5052 CB ASP 1244 5053 CG ASP 1244 5054 ODi ASP 1244 5055 0D2 ASP 1244 5056 C ASP 1244 5057 0 ASP 1244 5058 N GLY 1245 5059 H GLY 1245 5060 CA GLY 1245 5061 c GLY 1245 5062 o GLY 1245 5063 N LEU 1246 36.223 -18.933 31.805 1.00 31.30 37.045 -17.959 30.950 1.00 30.14 36.540 -20.398 31.541 1.00 28.41 35.805 -18.442 35.625 1.00 18.17 36.656 -18.766 36.475 1.00 19.31 35.110 -17.310 35.729 1.00 18.52 34.467 -17.041 35.035 1.00 0.00 35.258 -16.445 36.891 1.00 18.29 36.053 -15.163 36.596 1.00 17.78 37.404 -15.288 35.877 1.00 20.93 37.182 -15.155 34.356 1.00 26.47 38.487 -15.277 33.558 1.00 28.84 39.399 -14.166 33.786 1.00 31.56 39.650 -14.113 34.794 1.00 0.00 38.931 -13.284 33 .496 1.00 0.00 40.258 -14.304 33.217 1.00 0.00 33.857 -16.045 37.277 1.00 14.54 33.082 -15.650 36.417 1.00 14.69 33.500 -16.159 38.560 1.00 16.03 34.150 -16.545 39.191 1.00 0.00 32.167 -15.817 39.016 1.00 10.30 32.002 -16.130 40.481 1.00 10.45 31.876 -14.351 38.822 1.00 11. 11 30.729 -13 .955 38.615 1.00 18 .39 32.901 -13.511 38.964 1.00 13.67 33.748 -13 .880 39.280 1.00 0.00 32.808 -12.097 38.658 1.00 12.02 32.796 -12.085 37.119 1.00 17.69 32.791 -10.744 36.408 1.00 21.88 32.043 -10.598 35.445 1.00 22.59 33.537 -9.863 36.812 1.00 16.27 31.633 -11.379 39.334 1.00 11. 11 30.905 -10.591 38.733 1.00 12.88 31.431 -11.645 40.623 1.00 11.66 32.035 -12.271 41.067 1.00 0.00 30.360 -11.041 41.394 1.00 4.05 29.186 -11.970 41.654 1.00 6.06 28.328 -11.641 42.478 1.00 4.56 29.027 -13.078 40.924 1.00 6.26 S S 5555

S

555555

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55555*

S

ATOM

ATOM

ATOM

ATOM

ATOM

358

ATOM

ATOM

ATOM

ATOM

ATOM

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ATOM

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1 5 ATOM

ATOM

ATOM

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20 ATOM

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25 ATOM

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5064 5065 5066 5067 5068 5069 5070 5071 5072 5073 5074 5075 5076 5077 5078 5079 5080 5081 5082 5083 5084 5085 5086 5087 5088 5089 5090 5091 5092 5093 5094 5095 5096 5097 5098 5099 5100 5101 5102 H LEU 1246 CA LEU 1246 CB LEU 1246 CG LEU 1246 CD1 LEU 1246 CD2 LEU 1246 C LEU 1246 0 LEU 1246 N ILE 1247 H ILE 1247 CA ILE 1247 CB ILE 1247 CG2 ILE 1247 CG1 ILE 1247 CD ILE 1247 C ILE 1247 O ILE 1247 N TYR 1248 H TYR 1248 CA TYR 1248 CB TYR 1248 CG TYR 1248 CD1 TYR 1248 CEl TYR 1248 CD2 TYR 1248 CE2 TYR 1248 CZ TYR 1248 OH TYR 1248 HH TYR 1248 C TYR 1248 O TYR 1248 N CYS 1249 H CYS 1249 CA CYS 1249 CB CYS 1249 SG CYS 1249 C CYS 1249 O CYS 1249 N LEU 1250 29.670 -13.274 27.937 -14.037 27.839 -15.104 27.674 -14.752 27.924 -16.009 26.331 -14.139 28.187 -14.819 29.351 -14.975 27.168 -15.397 26.238 -15.238 27.449 -16.185 26.078 -16.432 25.248 -17.439 26.338 -16.845 25.094 -16.664 28.257 -17.473 28.851 -18.047 28.363 -17.894 27.947 -17.387 29.092 -19.088 28.289 -20.366 29.191 -21.564 29.429 -22.516 30.306 -23.572 29.824 -21.676 30.701 -22.732 30.935 -23.669 31.815 -24.695 31.879 -25.262 29.277 -19.017 28.492 -18.350 30.301 -19.689 30.939 -20.117 30.535 -19.856 31.812 -20.599 33.232 -19.521 29.460 -20.670 28.821 -21.562 29.284 -20.385 40.209 41.135 40.061 38.606 37.796 38.380 42.407 42.786 43.047 42.765 44.231 44 .900 44.094 46.362 47.211 43 .954 44.880 42.676 41.950 42 .274 42.625 42.880 41.885 42.130 44 .119 44.368 43.374 43.637 42.861 40.768 40.093 40.247 40.855 38.815 38.512 38.611 38.127 38.699 36.853 1.00 0.00 1.00 8.93 1.00 5.31 1.00 5.46 1.00 2.14 1.00 2.00 1.00 11.01 1.00 13.17 1.00 11.83 1.00 0.00 1.00 12.55 1.00 11.32 1.00 11.69 1 .00 4.92 1.00 2.58 -~00 16.34 1.00 13.40 1.00 15.02 1.00 0.00 1.00 12.39 1.00 9.23 1.00 8.97 1. 00 10.00 1.00 8.55 00 9.95 1 .00 6.09 1.00 3 .83 1.00 12.23 i .00 0.00 1.00 11.96 .00 10.19 1.00 12.38 1.00 0.00 1.00 17.03 1.00 14.50 1.00 29.55 1.00 14.34 1.00 15.48 1.00 13.47 -359 9*

ATOM

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ATOM

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ATOM

ATOM

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ATOM

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ATOM

15 ATOM

ATOM

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20 ATOM

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ATOM

ATOM

5103 5104 5105 5106 5107 5108 5109 5110 5111 5112 5113 5114 5115 5116 5117 5118 5119 5120 5121 5122 5123 5124 5125 5126 5127 5128 5129 5130 5131 5132 5133 5134 5135 5136 5137 5138 5139 5140 5141 H LEtJ CA LEU CB LELT CG LEU CD1 LEU CD2 LEIJ C LEU 0 LEU N LYS H LYS CA LYS CB LYS CG LYS CD LYS CE LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS O LYS N GLU H GLU CA GLU CB GLU CG GLU CD GLU OE1 GLU 0E2 GLU C GLU O GLU N ALA H ALA CA ALA CB ALA C ALA O ALA N CYS H CYS 1250 1250 1250 1250 1250 1250 1250 1250 1251 1251 1251 1251 1251 1251 1251 1251 1251 1251 1251 1251 1251 1252 1252 1252 1252 1252 1252 1252 1252 1252 1252 1253 1253 1253 1253 1253 1253 1254 1254 29.860 -19.715 28.363 -21.157 28.039 -20.406 27.434 -19.026 26.912 -18.579 26.318 -19.043 29.134 -22.439 30.301 -22.424 28.504 -23.545 27.570 -23.472 29.104 -24.851 29.070 -25.527 30.428 -25.703 31.108 -24.378 32.563 -24.607 32.687 -25.364 32.281 -26.314 32.183 -24.861 33.692 -25.446 28.355 -25.684 28.712 -25.723 27.241 -26.266 26.845 -25.961 26.502 -27.236 26.147 -28.341 25.066 -29.361 24.682 -30.193 25.571 -30.646 23.487 -30.392 25.294 -26.579 24.542 -25.938 25.134 -26.714 25.821 -27.186 23.974 -26.228 24.130 -26.360 22.785 -27.080 22.886 -28.304 21.668 -26.433 21.680 -25.457 36.427 36.061 34.787 34.950 33 .605 35.979 35.790 35 .407 36. 126 36.389 36.032 37.415 38.058 38.326 38.683 39.912 39.795 40. 672 40.160 35.012 33.829 35.447 36.290 34.685 35.653 35.347 36.571 37.298 36.804 34.093 34.821 32.776 32.272 32.050 30.548 32. 420 32.502 32.709 32.687 1. 00 0.00 '.00 14.95 1.00 7.93 1.00 3.87 1.00 2.00 1.00 8.53 1.00 15.93 1.00 19.86 1.00 17.94 1.00 0.00 1.00 21.49 1.00 19.69 1.00 24.61 1.00 26.63 1.00 32 1.00 38.55 1.00 0.00 1.00 0.00 1.00 0.00 1.00 21.80 1.00 26.89 1.00 18.32 1.00 0.00 1.00 16 .59 1.00 24.16 1.00 37.83 1.00 46.82 1.00 52.14 1.00 53.93 1.00 15.45 1.00 12.45 1.00 15.62 1.00 0.00 1.00 12.65 1.00 5.87 1.00 14.00 1.00 17.74 1.00 16.80 1.00 0.00 360 ATOM 5142 CA CYS 1254 20.428 -27.114 3252 10 148 32.952 1.00 14.88 ATOM 5143 CB CYS 1254 19.533 -26.275 33.838 1.00 7.31 ATOM 5144 SG CYS 1254 17.934 -27.060 34.181 1.00 11.48 ATOM 5145 C CYS 1254 19.843 -27.234 31.545 1.00 19.32 ATOM 5146 0 CYS 1254 19.494 -26.207 30.956 1.00 20.54 ATOM 5147 N PRO 1255 19.737 -28.427 30.937 1.00 24.66 ATOM 5148 CD PRO 1255 19.747 -29.716 31.620 1.00 23.90 ATOM 5149 CA PRO 1255 19.454 -28.617 29.522 1.00 25.94 ATOM 5150 CB PRO 1255 19.916 -30.024 29.277 1.00 25.59 1 0 ATOM 5151 CG PRO 1255 19.392 -30.703 30.520 1.00 25.86 ATOM 5152 c PRO 1255 17.998 -28.370 29.178 1.00 27.93 ATOM 5153 0 PRO 1255 17.101 -28.478 30.031 1.00 28.94 ATOM 5154 N ASN 1256 17.819 -27.884 27.961 1.00 33.02 *ATOM 5155 H ASN 1256 18.564 -27.819 27.329 1.00 0.00 1 5 ATOM 5156 CA ASN 1256 16.494 -27.679 27.418 1.00 36.15 .ATOM 5157 CB ASM 1256 16.500 -26.480 26.412 1.00 40.46 :::ATOM 5158 CG ASN 1256 17.538 -26.371 25.280 1.00 43.38 ATOM 5159 ODi ASN 1256 18.465 -27.162 25.085 1.00 49.15 ATOM 5160 ND2 ASN 1256 17.492 -25.289 24.509 1.00 47.41 20 ATOM 5161 HD21 ASN 1256 16.828 -24.602 24.706 1.00 0.00 ATOM 5162 HD22 ASN 1256 18.165 -25.229 23.805 1.00 0.00 *ATOM 5163 C ASN 1256 16.026 -28.969 26.747 1.00 37.74 ATOM 5164 0 ASN 1256 14.817 -29.127 26.588 1.00 40.27 ATOM 5165 OT ASN 1256 16.858 -29.832 26.440 1.00 37.85 25 ATOM 5166 CE ASN 1301 9 .323 -7.474 39.011 1.00 72.83 ATOM 5167 CG ASN 1301 8.164 -8.460 38.892 1.00 75.21 ATOM 5168 001 ASN 1301 8.313 -9.453 38.175 1.00 77.67 ATOM 5169 ND2 ASN 1301 7.018 -8.265 39.523 1.00 73.86 ATOM 5170 HD21 ASN 1301 6.864 -7.453 40.049 1.00 0.00 ATOM 5171 HD22 ASN 1301 6.359 -8.991 39.479 1.00 0.00 ATOM 5172 C ASN 1301 10.948 -9.156 40.037 1.00 69.93 ATOM 5173 0 ASN 1301 11.680 -10.106 39.751 1.00 71.07 ATOM 5174 HT1 ASN 1301 10.055 -9.516 37.599 1.00 0.00 ATOM 5175 HT2 ASN 1301 11.673 -9.582 37.951 1.00 0.00 ATOM 5176 N ASN 1301 10.898 -8.913 37.721 1.00 71.59 ATOM 5177 HT3 ASN 1301 11.124 -8.372 36.873 1.00 0.00 ATOM 5178 CA ASN 1301 10.741 -8.118 38.933 1.00 71.90 ATOM 5179 N GLN 1302 10.329 -9.121 41.226 1.00 66.66 ATOM 5180 H GLN 1302 9.648 -8.440 41.394 1.00 0.00 361 ATOM 5181 CA GLN 1302 10.602 -10.0134.36 106.9 42.356 1.00 61.49

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5182 5183 5184 5185 5186 5187 5188 5189 5190 5191 5192 5193 5194 5195 5196 5197 5198 5199 5200 5201 5202 5203 5204 5205 5206 5207 5208 5209 5210 5211 5212 5213 5214 5215 5216 5217 5218 5219 CB GLN 1302 CG GLN 1302 CD GLN 1302 OE1 GLN 1302 NE2 GLN 1302 HE21 GLN 1302 HE22 GLN 1302 C GLN 1302 O GLN 1302 N LEU 1303 H LEU 1303 CA LEU 1303 CB LEU 1303 CG LEU 1303 CD1 LEU 1303 CD2 LEU 1303 C LEU 1303 O LEU 1303 N PTY 1304 H PTY 1304 CA PTY 1304 CB PTY 1304 CG PTY 1304 CD1 PTY 1304 CEl PTY 1304 CD2 PTY 1304 CE2 PTY 1304 CZ PTY 1304 OH PTY 1304 ORi PTY 1304 0R2 PTY 1304 0R3 PTY 1304 PR PTY 1304 C PTY 1304 O PTY 1304 N ASN 1305 H ASM 1305 CA ASN 1305 10.414 9.203 7 .876 7 .588 7 .015 7.256 6.171 12.043 12.552 12.761 12.476 14.082 14.394 13 .555 13 .147 12.345 15 .145 15 .238 15.912 15.739 17 .072 17.224 16.247 16.425 15.461 15.081 14.127 14.290 13.224 11.117 12.831 11.748 12.271 18.265 18.382 19 .163 19 .013 20.348 -11. 513 -11.902 -11. 373 -10. 173 -12.263 -13.211 -11.916 -9.756 -8.645 -10.678 -11.612 -10. 350 -11. 073 -11.102 -9.676 -12.030 -10.760 -11.950 -9.820 -8.867 -10.190 -9.402 -9.844 -11.042 -11.487 -9.117 -9.556 -10.742 11. 076 -11.770 -13.521 -12.738 -12.339 -9.885 871 -10.830 -11.584 -10.769 41.988 41. 135 41. 651 41. 632 42.117 42.101 42 .471 42.803 42.573 43.432 43 .456 43.932 45 .273 46.592 46.963 46.439 42.930 42.605 42.382 42.521 41.594 40.276 39.214 38.469 37.558 38.994 38.083 37.368 36.557 37 .454 37.365 35.436 36.718 42.458 43 .148 42.439 41.839 43.231 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 62 .07 62 .59 64.61 60.30 66.75 0.00 0.00 56.80 58.90 49.38 0.00 43 .43 51.18 54.39 55.27 52.47 35.27 32.57 27.69 0.00 21.92 20.89 15.14 9.03 7.86 14.16 16.68 12.39 13.70 13.77 17.79 12 .59 16.46 17 .48 20.06 11.57 0.00 10. 89 362

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5260 CA 5261 CB 5262 CG 5263 CD1 5264 CD2 5265 c 5266 0 5267 N 5268 H 5269 CA 5270 C 5271 0 5272 N 5273 H 5274 CA 5275 CB 5276 CG 5277 CD 5278 NE 5279 HE 5280 CZ 5281 NH1 5282 HH11 5283 HH12 5284 NH2 5285 HH21 5286 HH22 5287 C 5288 0 5289 N 5290 H 5291 CA 5292 CB 5293 CG 5294 CD 5295 NE 5296 HE 5297 CZ LEU 1309 LEU 1309 LEU 1309 LEt! 1309 LEt! 1309 LEU 1309 LEt! 1309 GLY 1310 GLY 1310 GLY 1310 GLY 1310 GLY 1310 ARG 1311 ARG 1311 ARG 1311 ARG 1311 ARG 1311 ARG 1311 ARG 1311 ARG 1311 ARG 1311 ARG 1311 ARG 1311 ARG 1311 AG1311 ARG 1311 ARG 1311 ARG 1311 ARG 1311 ARG 1312 ARG 1312 ARG 1312 ARG 1312 ARG 1312 ARG 1312 ARG 1312 ARG 1312 ARG 1312 31.392 30.962 29 .980 28.777 29 .492 32.841 33.700 33 .179 32.490 34.577 35.074 36.249 34.210 33 .270 34.616 33 .672 34.141 35 .342 35.599 34.910 36.749 37.744 37.646 38.588 36.902 36.168 37 .757 34.620 34.700 34. 476 34 .477 34.500 33.926 32.424 32 .166 33.042 33 .472 33 .309 -5 .992 -4.545 -3 .827 -4 .662 -2.563 -6.177 -5 .840 -6.740 -7.028 -7 .013 -8.325 -8.662 -9.106 -8.844 -10.357 -11.452 -12 .201 -13 .058 -14.117 -14.798 -14.216 -13 .337 -12 .581 -13.433 -15.213 -15 .876 -15.294 -10.284 -11.280 -9 .062 -8.309 -8 .764 -7.381 -7.339 -6 .440 -6.760 -7.639 -5.896 43.662 43.948 42.984 42.645 43.662 44.027 43.220 45.192 45.825 45.518 44.899 45.035 44.230 44.178 43.608 44.107 45.357 44.978 45.937 46.082 46.617 46.455 45.806 46.982 47.494 47.633 48.007 42.079 41. 345 41.589 42.214 40.177 39.926 39.718 38.507 37.375 37.346 36.376 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1. 00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1 00o 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 18.16 14.91 20.31 20.12 22.61 18.95 19.70 24.64 0.00 21.96 25.29 25 .13 25.06 0.00 28.30 34.71 39.05 48.06 55.93 0.00 63 .14 67.95 0.00 0.00 66.62 0 .00 0.00 27 .99 30.80 25.90 0.00 21.56 20.04 21.41 25.51 23.48 0.00 30.45 364 ATOM 5298 NH1 ARG 1312 ATOM 5298 NH1ARG 312 32.789 -4.660 36.302 1.00 24.19 0See 6@ S.

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5338 5339 5340 5341 5342 5343 5344 5345 5346 5347 5348 5349 5350 5351 5352 5353 5354 5355 5356 5357 5358 5359 5360 5361 5362 5363 5364 5365 536.6 5367 5368 5369 5370 5371 5372 5373 5374 5375 OR2 PTY 1315 OR3 PTY 1315 PR PTY 1315 C PTY 1315 O PTY 1315 N ASP 1316 H ASP 1316 CA ASP 1316 CB ASP 1316 CG ASP 1316 OD1 ASP 1316 OD2 ASP 1316 C ASP 1316 O ASP 1316 N VAL 1317 H VAL 1317 CA VAL 1317 CB VAL 1317 CG1 VAL 1317 CG2 VAL 1317 C VAL 1317 O VAL 1317 N LEU 1318 H LEU 1318 CA LEU 1318 CB LEU 1318 CG LEU 1318 CD1 LEU 1318 CD2 LEU 1318 C LEU 1318 O LEU 1318 N ASP 1319 H ASP 1319 CA ASP 1319 CB ASP 1319 CG ASP 1319 OD1 ASP 1319 OD2 ASP 1319 41.612 40.109 40.190 41.937 41.713 42.895 42.989 43.655 45.127 45.767 46.533 45.509 43.193 42.724 43.280 43.722 42.948 41.791 42.225 41.280 44.269 45.215 44.340 43.558 45.520 45.299 44.989 44.192 46.238 45.793 44.861 47.101 47.696 47.709 49.218 49.622 50.483 49.104 -10.940 -12.344 -11.164 -3.825 -3.239 -3.433 -3.813 -2.257 -2.491 -3.314 -2.742 -4.514 -1.143 -1.390 0.085 0.236 1.243 2.049 2.723 3.069 2.008 1.761 2.869 2.982 3.675 4.414 3.532 4.345 3.003 4.633 5.114 4.744 4.244 5.555 5.246 3.840 3.737 2.855 31.097 29.936 30.804 34.101 35.167 33.300 32.405 33.639 33.430 34.519 35.291 34.583 32.733 31.615 33.229 34.088 32.418 33.116 34.411 32.112 32.319 33.089 31.308 30.733 31.063 29.757 28.554 27.606 27.888 32.222 32.887 32.471 31.885 33.519 33.704 34.143 35.019 33.607 1.00 22.23 1.00 21.17 1.00 16.43 1.00 28.24 1.00 34.41 1.00 30.96 1.00 0.00 1.00 37.10 1.00 41.47 1.00 45.09 1.00 51.31 1.00 47.70 1.00 39.53 1.00 45.74 1.00 41.83 1.00 0.00 1.00 44.85 1.00 43.64 1.00 46.74 1.00 46.56 1.00 45.31 1.00 41.69 1.00 45.11 1.00 0.00 1.00 47.99 1.00 42.85 1.00 38.00 1.00 32.68 1.00 34.68 1.00 53.72 1.00 53.92 1.00 60.15 1.00 0.00 1.00 67.37 1.00 71.97 1.00 75.12 1.00 75.09 1.00 75.64 366 ATOM 5376 ATOM 5377 ATOM 5378 ATOM 5379 ATOM 5380 ATOM 5381 ATOM 5382 ATOM 5383 ATOM 5384 ATOM 5385 ATOM 5386 ATOM 5387 ATOM 5388 ATOM 5389 15 ATOM 5390 ATOM 5391 ATOM 5392 ATOM 5393 ATOM 5394 ATOM 5395 ATOM 5396 ATOM 5397 ATOM 5398 ATOM 5399 25 ATOM 5400 ATOM 5401 ATOM 5402 ATOM 5403 ATOM 5404 ATOM 5405 ATOM 5406 ATOM 5407 ATOM 5408 ATOM 5409 ATOM 5410 ATOM 5411 ATOM 5412 ATOM 5413 ATOM 5414 C ASP O ASP OT ASP OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 H1 H20 H2 H20 OH2 H20 H1 H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 1319 1319 1319 2091 2091 2091 2289 2289 2289 2003 2003 2003 2035 2035 2035 2230 2230 2230 2226 2226 2226 2235 2235 2235 2367 2267 2367 2:77 2277 2217 2217 2217 2021 2021 2021 2265 2265 2265 47.599 48.000 47.117 11.613 11.021 12.286 -0.606 -0.216 -1.566 -4.862 -5.578 -5.228 0.414 0.960 -0.430 -3.731 -3.892 -2.780 4.474 3.910 4.883 5.036 4.530 5.003 6.779 6.838 7.586 0.582 0.905 -0.256 2.900 3.827 2.421 5.582 6.399 6.035 7.276 7.061 8.249 7.036 7.450 7.758 6.292 6.247 6.908 1.712 1.680 1.715 -2.850 -2.602 -3.616 8.828 8.879 9.187 1.596 1.670 1.688 -1.056 -1.250 -1.923 1.440 1.009 0.712 5.277 4.525 5.141 2.614 1.731 2.437 -2.745 -2.865 -3.213 -3.229 -3.389 -2.957 -2.450 -1.547 -2.355 33.206 32.113 34.075 3.790 3.030 3.506 22.323 23.198 22.535 17.008 16.416 17.461 19.112 19.902 19.400 4.235 3.275 4.279 -2.417 -1.642 -2.534 -3.371 -4.064 -2.714 -2.088 -2.722 -1.574 -1.861 -1.641 -2.298 -0.055 0.230 0.635 0.413 0.934 -0.416 -1.549 -1.814 -1.576 1.00 69.96 1.00 72.41 1.00 72.49 1.00 9.15 1.00 0.00 1.00 0.00 1.00 38.94 1.00 0.00 1.00 0.00 1.00 55.78 1.00 0.00 1.00 0.00 1.00 32.59 1.00 0.00 1.00 0.00 1.00 7.64 1.00 0.00 1.00 0.00 1.00 39.20 1.00 0.00 1.00 0.00 1.00 34.16 1.00 0.00 1.00 0.00 1.00 14.63 1.00 0.00 1.00 0.00 1.00 15.62 1.00 0.00 1.00 0.00 1.00 18.30 1.00 0.00 1.00 0.00 1.00 12.00 1.00 0.00 1.00 0.00 1.00 19.34 1.00 0.00 1.00 0.00 a a a.aa 367 ATOM 5415 OH2 H20 2050 9.531 -1.039 -1.954 1.00 15.27

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5416 5417 5418 5419 5420 5421 5422 5423 5424 5425 5426 5427 5428 5429 5430 5431 5432 5433 5434 5435 5436 5437 5438 5439 5440 5441 5442 5443 5444 5445 5446 5447 5448 5449 5450 5451 5452 5453 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 H1 H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 1H H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 2050 2050 2188 2188 2188 2106 2106 2106 2263 2263 2263 2369 2369 2369 2336 2336 2336 2005 2005 2005 2013 2013 2013 2210 2210 2210 2397 2397 2397 2211 2211 2211 2088 2088 2088 2127 2127 2127 9.759 10.415 7.944 8.919 7.784 11.995 12.822 12.292 10.556 9.920 11.186 7.366 6.788 8.158 2.623 3.445 2.231 6.010 5.210 5.836 8.688 7.716 8.704 -1.947 -1.077 -1.901 6.940 6.259 7.709 5.320 5.164 5.887 6.170 5.979 6.024 4.543 4.355 5.174 -0.600 -1.132 -3.913 -3.847 -4.090 -1.225 -1.128 -1.014 -3.103 -2.379 -2.784 -4.615 -3.949 -4.482 -5.870 -5.538 -5.086 3.922 3.992 3.150 3.977 3.844 4.934 22.873 23.018 21.999 3.302 2.617 2.739 7.091 6.691 6.432 9.583 9.263 8.768 11.747 11.872 10.996 -2.781 -1.532 1.547 1.542 2.502 -0.912 -1.408 -0.019 2.014 2.027 1.353 4.091 4.488 4.669 6.276 5.917 6.672 2.813 2.283 3.362 2.421 2.522 2.501 18.487 18.107 18.875 -4.007 -3.809 -4.215 -4.231 -5.096 -3.794 -5.206 -6.114 -4.695 -5.012 -5.943 -5.030 1.00 0.00 1.00 0.00 1.00 6.13 1.00 0.00 1.00 0.00 1.00 10.49 1.00 0.00 1.00 0.00 1.00 16.72 1.00 0.00 1.00 0.00 1.00 8.30 1.00 0.00 1.00 0.00 1.00 8.51 1.00 0.00 1.00 0.00 1.00 5.77 1.00 0.00 1.00 0.00 1.00 4.93 1.00 0.00 1.00 0.00 1.00 21.45 1.00 0.00 1.00 0.00 1.00 14.99 1.00 0.00 1.00 0.00 1.00 5.91 1.00 0.00 1.00 0.00 1.00 3.99 1.00 0.00 1.00 0.00 1.00 17.56 1.00 0.00 1.00 0.00 368 ATOM 5454 OH2 H20 2393 ATOM 5454 0112H20 3934.660 15.853 -4.263 1.00 17.70 a a a

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5455 5456 5457 5458 5459 5460 5461 5462 5463 5464 5465 5466 5467 5468 5469 5470 5471 5472 5473 5474 5475 5476 5477 5478 5479 5480 5481 5482 5483 5484 5485 5486 5487 5488 5489 5490 5491 5492 Hl H20 H2 H120 0112 H20 Hi H120 H2 H120 0H2 H20 H1 H120 H2 H120 012 1120 Hi H20 H2 H20 0112 H20 Hi H20 H2 H120 0H2 H120 Hl 1120 H2 H20 0H2 H20 Hl H120 H2 H120 0H2 1120 Hi H20 H12 H20 0H2 H20 Hi H20 H2 1120 0112 H20 Hl H20 H2 H20 0H2 1120 Hl H20 12 1120 0H2 1120 Hl H120 H2 H120 0112 H20 Hl H120 H2 H20 2393 2393 2363 2363 2363 2252 2252 2252 2337 2337 2337 2447 2447 2447 2131 2131 2131 2012 2012 2012 2323 2323 2323 2037 2037 2037 2428 2428 2428 2017 2017 2017 2219 2219 2219 2262 2262 2262 4.191 3 .945 1.201 0.982 0.630 7.730 7.37 6.918 -0.119 -0.770 0.699 -0 .079 -0.141 -0.776 -2.231 -2.931 -2.407 -7.124 847 -6.813 -7.338 -7 .697 -7 .245 -7.188 -7 .947 -6.730 -10.421 -9 .470 -10.709 -8.108 -8.845 -7 .664 -10.483 -11.182 -10.338 -12.360 -11.954 -13.288 16.391 15.378 14.180 14.252 13.434 13.503 12.604 14.021 11.846 11.321 11.419 10.337 11.081 9.752 7.960 7.867 7.253 7.460 8 .045 7 .923 5 .501 4.705 6 .096 10.431 11.011 10.509 9.838 9.846 10.567 10.668 11.291 10.692 12.122 12.413 12.947 13.300 14.149 13.532 -4.706 -4.789 -3.860 -5.056 -4.221 -4.201 -4.319 -4.785 -4.302 -4.499 -7.542 -6.922 -7.213 -6.047 -5.394 -6.673 -2.263 -1.992 -3.054 -0.353 -0.764 -1.135 -4.834 -4.942 -5.672 2.454 2.679 3.029 3.645 3.785 4.498 3.962 3.328 4.438 2.252 2.024 .2.382 1.00 0.00 1.00 14.09 1.00 0.00 1.00 0.00 1.00 26.93 1.00 0.00 1.00 0.00 1.00 11.20 1.00 0.00 1.00 0.00 1.00 40.91 1.00 0.00 1.00 0.00 1.00 23.04 1.00 0.00 1.00 0.00 1.00 20.39 1.00 0.00 1.00 0.00 1.00 64.57 1.00 0.00 1.00 0.00 1.00 18.12 1.00 0.00 1.00 0.00 1.00 48.35 1.00 0.00 1.00 0.00 1.00 7.28 1.00 0.00 1.00 0.00 1.00 33 1.00 0.00 1.00 0.00 1.00 20.55 1.00 0.00 1.00 0.00 -3.624 1.00 0.00 369 ATOM 5493 OH2 H20 2381 ATO 593 0H282 281 -11.522 8.285 0.417 1.00 28.89

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S S ATOM 5494 Hi 820 ATOM 5495 H2 H20 ATOM 5496 082 H2O ATOM 5497 Hi H2O ATOM 5498 H2 H20 ATOM 5499 082 820 ATOM 5500 Hi 820 ATOM 5501 H2 H20 1 0 ATOM 5502 0H2 H20 ATOM 5503 Hi 820 ATOM 5504 82 H20 ATOM 5505 082 820 ATOM 5506 H1 H20 1 5 ATOM 5507 H2 H20 ATOM 5508 0H2 820 ATOM 5509 Hl 820 ATOM 5510 82 H20 ATOM 5511 082 H20 ATOM 5512 Hi H20 ATOM 5513 82 820 ATOM 5514 082 820 ATOM 5515 Hi H20 ATOM 5516 82 820 ATOM 5517 082 820 ATOM 5-518 81 820 ATOM 5519 82 820 ATOM 5520 082 820 ATOM 5521 Hl 820 ATOM 5522 82 820 ATOM 5523 082 820 ATOM 5524 81 820 ATOM 5525 82 820 ATOM 5526 082 820 ATOM 5527 H1 820 ATOM 5528 82 820 ATOM 5529 082 820 ATOM 5530 H1 820 2381 2381 2245 2245 2245 2339 2339 2224 2224 2224 2157 2157 2157 2248 2248 2248 228 2283 2283 2255 2255 2255 2237 2237 2237 2236 2236 2236 2232 2032 2032 2034 2384 2384 2084 2008 -11.065 8.791 -12.392 8.682 -9.256 20.762 -10.180 21.032 -9.310 19.800 -6.000 18.865 -6.887 19.186 -9.178 21.950 -8.297 22.121 -8.945 21.700 11.171 -10.628 10.586 -9.878 10.577 -11.117 -6.862 19.924 -7.017 19.074 -6.417 20.445 -4.214 19.691 -4.833 19.464 -3.531 20.196 -3.770 23.422 -3.036 22.810 -4.446 22.840 -1.087 23.450 -1.236 22.495 -1.995 23.715 -2.200 7.603 -1.248 7.737 -2.478 7.806 9.637 -4.335 9.827 -4.315- 10.503 -4.129 8.433 -8.052 8.776 -8.614 7.535 -8.400 10.386 -0.880 10.921 -1.130 9.704 -0.366 1.123 0.427 7.011 6.982 6.966 9.435 9.244 4.490 4.123 5.404 -3.794 -4.046 -3.221 0.800 0.361 0.127 11.429 10.706 10.967 11.688 11.546 12.045 4.984 5 .008 4.776 3.264 3.328 4.166 5.775 6.735 5.414 11.060 10.352 11.097 7.792 7.031 7.345 1.00 0.00 1.00 0.00 1.00 26.26 1.00 0.00 1.00 0.00 1.00 27.95 1.00 0.00 1.00 14.21 1.00 0.00 1.00 0.00 1.00 7.88 1.00 0.00 1.00 0.00 1.00 20.11 1.00 0.00 1.00 0.00 1.00 12.06 1.00 0.00 1.00 0.00 1.00 11.13 1.00 0.00 1.00 0.00 1.00 5.75 1.00 0.00 1.00 0.00 1.00 94.00 1.00 0.00 1.00 0.00 1.00 22.19 1.00 0.00 1.00 0.00 1.00 48.89 1.00 0.00 1.00 0.00 1.00 3.56 1.00 0.00 1.00 0.00 ATOM 5531 82 820 2008 370

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5532 5533 5534 5535 5536 5537 5538 5539 5540 5541 5542 5543 5544 5545 5546 5547 5548 5549 5550 5551 5552 5553 5554 5555 5556 5557 5558 5559 5560 5561 5562 5563 5564 5565 5566 5567 5568 5569 5570 0H2 H20 Hl H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hl H20 H2 H20 0H2 H20 Hl H20 H2 H20 01-2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H12 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 01-2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 2019 2019 2019 2048 2048 2048 2028 2028 2028 2051 2051 2051 2390 2390 2390 2416 2416 2416 2278 2278 2278 2241 2241 2241 2330 2330 -330 2319 2319 2319 2129 2129 2129 24 05 2 40 5 2405 2002 2002 2002 10.216 9.397 10.150 13 .175 12.391 12.850 14.613 13.928 14.201 14.444 14. 489 15.329 7.071 7 .620 7.141 7.110 7 .917 6.872 2 .347 1.432 2 .313 4.928 4.055 5.389 5.495 5 .618 4.537 9.830 10.441 9 .294 8.201 7.738 8.316 10.491 10.534 9.584 15.026 15.184 15.740 -3 .653 -3.758 -2.713 4 .924 5.233 4.832 -6 .647 819 -5.975 1.482 0.558 1. 607 26.689 27.385 26.008 24.301 24.786 24.654 20.840 20.561 21.668 19.565 19 .952 19 .661 19 .739 19.333 19 .756 15.311 14.835 15 .773 16.349 17 .108 16 .597 14.246 14.843 13 891 10 .845 11.736 10 .321 8.487 9.015 8.232 8.006 7.536 8.910 11. 993 11.337 12.541 10.802 11.082 10. 393 10.142 10.523 10.831 5.255 5.458 4.389 -2.242 -2 .127 -1.736 -1.717 -1.941 -2.552 11.331 12.203 11. 269 2.100 1.515 1.419 0.185 0.561 -0.737 -3.600 -4.349 -3 .697 9.558 9.185 9 .146 1.00 19.93 1.00 0.00 1.00 0.00 1.00 15.14 1.00 0.00 1.00 0.00 1.00 18.49 i.00 0.00 1.00 0.00 1.00 2.00 1.00 0.00 1.00 0.00 1.00 64.54 1.00 0.00 1.00 0.00 1.00 25.90 1.00 0.00 1.00 0.00 1.00 25.42 1.00 0.00 1.00 0.00 1.00 13.89 1.00 0.00 1.00 0.00 1.00 89.21 1.00 0.00 1.00 0.00 1.00 15.29 1.00 0.00 1.00 0.00 1.00 20.32 1.00 0.00 1.00 0.00 1.00 13.44 1.00 0.00 1.00 0.00 1.00 3.64 1.00 0.00 1.00 0.00 371 ATOM 5571 0H2 H20 2104 15.471 13.315 8.633 1.00 17.22 ATOM 5572 Hl H20 2104 14.807 13.835 8.155 1.00 0.00 ATOM 5573 H2 H20 2104 15.759 13.928 9.338 1.00 0.00 ATOM 5574 OH2 H2O 2437 17.011 9.295 8.530 1.00 20.44 ATOM 5575 Hi H20 2437 16.669 8.421 8.295 1.00 0.00 ATOM 5576 H2 H20 2437 17.919 9.230 8.217 1.00 0.00 ATOM 5577 0H2 H20 2128 17.124 10.103 3.658 1.00 38.97 ATOM 5578 H1 H20 2128 16.954 10.675 4.434 1.00 0.00 ATOM 5579 H2 H20 2128 17.281 10.773 2.990 1.00 0.00 ATOM 5580 0H2 H20 2083 18.716 6.786 5.655 1.00 38.25 ATOM 5581 Hi H20 2083 18.094 6.062 5.812 1.00 0.00 ATOM 5582 H2 H20 2083 18.449 7.120 4.794 1.00 0.00 ATOM 5583 0H2 H20 2167 18.412 8.237 1.848 1.00 17.94 .e.*ATOM 5584 Hi H20 2167 17.942 8.754 2.529 1.00 0.00 ATOM 5585 H2 H20 2167 19.202 8.789 1.688 1.00 0.00 *ATOM 5586 0H2 H20 2026 15.879 5.673 7.246 1.00 48.02 *ATOM 5587 Hi H20 2026 14.941 5.437 7.369 1.00 0.00 **ATOM 5588 H2 H20 2026 16.175 5.047 6.554 1.00 0.00 ATOM 5589 0H2 H20 2049 17.314 7.977 13.797 1.00 16.58 ATOM 5590 Hi H20 2049 16.400 8.007 13.482 1.00 0.00 ATOM 5591 H2 H20 2049 17.375 7.066 14.141 1.00 0.00 ATOM 5592 0H2 H20 2228 20.491 10.527 13.557 1.00 79.19 *ATOM 5593 HI H20 2228 21.024 9.803 13.223 1.00 0.00 ATOM 5594 H2 H20 2228 19.983 10.083 14.274 1.00 0.00 ATOM 5595 0H2 H20 2247 18.848 9.457 15.383 1.00 28.02 ATOM 5596 Hi H20 2247 18.287 8.895 14.791 1.00 0.00 ATOM 5597 H2 H20 2247 18.206 9.713 16.054 1.00 0.00 ATOM 5598 0H2 H20 2189 7.177 0.098 20.558 1.00 12.38 ATOM 5599 Hl H20 2189 7.665 -0.699 20.329 1.00 0.00 ATOM 5600 H2 H20 2189 7.855 0.612 21.009 1.00 0.00 ATOM 5601 0H2 H20 2153 10.987 -2.027 19.374 1.00 30.53 ATOM 5602 Hi H20 2153 11.365 -1.186 19.661 1.00 0.00 ATOM 5603 H2 H20 2153 10.534 -1.780 18.559 1.00 0.00 ATOM 5604 0H2 H20 2387 15.573 -5.220 22.034 1.00 26.88 ATOM 5605 HI H20 2387 15.420 -4.414 22.537 1.00 0.00 ATOM 5606 H2 H20 2387 15.880 -4.902 21.183 1.00 0.00 ATOM 5607 0H2 H20 2081 11.585 0.443 22.679 1.00 18.85 ATOM 5608 Hi H20 2081 10.705 0.405 22.293 1.00 0.00 ATOM 5609 H2 H20 2081 12.133 0.412 21.891 1.00 0.00 372 ATOM 5610 OH2 H20 2065 ATOM 5611 HI H20 2065 ATOM 5612 H2 H20 2065 ATOM 5613 OH2 H20 2307 ATOM 5614 H1 H20 2307 ATOM 5615 H2 H20 2307 ATOM 5616 OH2 H20 2174 ATOM 5617 HI H20 2174 ATOM 5618 H2 H20 2174 ATOM 5619 OH2 H20 2080 ATOM 5620 HI H20 2080 ATOM 5621 H2 H20 2080 ATOM 5622 OH2 H20 2145 ATOM 5623 HI H20 2145 15 ATOM 5624 H2 H20 2145 ATOM 5625 OH2 H20 2234 ATOM 5626 H1 H20 2234 ATOM 5627 H2 H20 2234 ATOM 5628 OH2 H20 2389 ATOM 5629 H1 H20 2389 ATOM 5630 H2 H20 2389 ATOM 5631 OH2 H20 2442 ATOM 5632 HI H20 2442 ATOM 5633 H2 H20 2442 ATOM 5634 OH2 H20 2294 ATOM 5635 H1 H20 2294 ATOM 5636 H2 H20 2294 ATOM 5637 OH2 H20 2435 ATOM 5638 HI H20 2435 ATOM 5639 H2 H20 2435 ATOM 5640 OH2 H20 2195 ATOM 5641 HI H20 2195 ATOM 5642 H2 H20 2195 ATOM 5643 OH2 H20 2292 ATOM 5644 H1 H20 2292 ATOM 5645 H2 H20 2292 ATOM 5646 OH2 H20 2445 ATOM 5647 HI H20 2445 ATOM 5648 H2 H20 2445 12.905 12.163 13.497 13.198 14.125 16.345 15.955 17.276 16.899 16.192 17.504 8.985 8.457 8.932 -1.344 -1.446 -1.080 -1.529 -1.103 -1.683 -4.227 -4.311 -3.299 -1.737 -1.393 -2.553 3.968 4.484 3.362 -2.103 -1.333 -2.463 4.660 3.750 4.768 7.938 8.797 7.479 11.565 17.437 12.420 16.446 15.746 18.110 16.526 17.607 16.164 18.711 14.884 10.755 14.561 11.582 14.775 10.999 10.708 22.439 10.707 23.107 10.070 22.839 6.741 24.686 7.507 24.413 6.789 25.642 12.735 21.035 12.294 20.176 13.620 20.775 11.859 18.208 11.457 17.445 12.782 17.891 11.513 17.909 12.468 17.887 11.412 18.188 4.678 21.101 5.578 21.112 4.753 21.611 2.794 20.047 1.976 19.985 2.571 20.765 14.513 17.363 15.013 17.684 15.110 16.687 24.323 21.790 24.146 21.548 23.824 22.603 18.020 26.568 18.087 27.007 17.386 27.129 1.00 0.00 1.00 0.00 1.00 21.94 1.00 0.00 1.00 0.00 1.00 12.56 1.00 0.00 1.00 0.00 1.00 18.59 1.00 0.00 1.00 0.00 1.00 10.42 1.00 0.00 1.00 0.00 1.00 32.56 1.00 0.00 1.00 0.00 1.00 25.81 1.00 0.00 1.00 0.00 1.00 40.21 1.00 0.00 1.00 0.00 1.00 50.85 1.00 0.00 1.00 0.00 1.00 20.89 1.00 0.00 1.00 0.00 1.00 45.39 1.00 0.00 1.00 0.00 1.00 31.24 1.00 0.00 1.00 0.00 1.00 33.41 1.00 0.00 1.00 0.00 12.324 11.499 16.673 1.00 6.58 r 373 ATOM 5649 0H2 H20 2400 10.560 23.286 20.157 1.00 25.80 ATOM 5650 H1 H20 2400 10.053 24.081 19.966 1.00 0.00 ATOM 5651 H2 H20 2400 11.446 23.627 20.311 1.00 0.00 ATOM 5652 082 H2O 2427 10.358 23.548 15.422 1.00 19.65 ATOM 5653 H1 H2O 2427 9.950 23.212 14.607 1.00 0.00 ATOM 5654 H2 H20 2427 10.834 24.319 15.099 1.00 0.00 ATOM 5655 082 H20 2275 -11.995 7.700 8.856 1.00 56.20 Hi H20 2-275 -11.299 7.070 9.091 1.00 0-00 ATOM 5657 H2 820 2275 -11.495 8.399 8.430 1.00 0.00 1 0 ATOM 5658 0H2 H20 2253 -10.228 1.870 9.007 1.00 15.68 ATOM 5659 Hi H20. 2253 -9.398 1.562 8.616 1.00 0.00 ATOM 5660 H2 H20 2253 -10.313 2.724 8.562 1.00 0.00 ATOM 5661 082 H20 2076 7.254 -10.240 9.154 1.00 13.69 *e.ATOM 5662 Hi 820 2076 7.440 -11.075 9.629 1.00 0.00 1 5 ATOM 5663 H2 820 2076 6.947 -10.557 8.294 1.00 0.00 *ATOM 5664 082 820 2191 14.696 -18.909 5.506 1.00 21.42 .ATOM 5665 Hi 820 2191 13.932 -18.906 6.088 1.00 0.00 ATOM 5666 H2 820 2191 14.993 -17.999 5.512 1.00 0.00 ATOM 5667 0H2 H20 2025 13.620 -17.448 15.050 1.00 16.30 ATOM 5668 Hi H20 2025 13.150 -16.664 15.367 1.00 0.00 ATOM 5669 H2 H20 2025 12.888 -18.073 15.081 1.00 0.00 ATOM 5670 082 820 2184 19.050 -19.408 16.078 1.00 37.17 *ATOM 5671 Hl 820 2184 18.624 -19.737 15.276 1.00 0.00 ATOM 5672 82 H20 2184 19.972 -19.612 15.906 1.00 0.00 ATOM 5673 082 820 2429 11.300 -29.483 9.061 1.00 46.58 *ATOM 5674 Hl 820 2429 12.135 -29.548 8 .589 1.00 0.00 *ATOM 5675 82 820 2429 11.528 -28.904 9.800 1.00 0.00 ATOM 5676 082 820 2196 4.962 -12.445 14.206 1.00 55.45 ATOM 5677 H1 820 2196 4.086 -12.167 14.476 1.00 0.00 ATOM 5678 82 820 2196 5.364 -11.658 13.839 1.00 0.00 ATOM 5679 082 820 2426 7.900 -12.611 10.746 1.00 23.66 ATOM 5680 Hl 820 2426 8.783 -12.871 11.025 1.00 0.00 ATOM 5681 82 820 2426 7.348 -13.325 11.080 1.00 0.00 ATOM 5682 082 820 2052 10.898 -6.045 11.814 1.00 25.42 ATOM 5683 H1 820 2052 10.206 -6.592 11.412 1.00 0.00 ATOM 5684 82 820 2052 10.931 -6.401 12.704 1.00 0.00 ATOM 5685 082 820 2103 15.818 -19.257 15.652 1.00 72.28 ATOM 5686 81 820 2103 15.184 -18.542 15.441 1.00 0.00 ATOM 5687 82 820 2103 16.640 -18.781 15.841 1.00 0.00 374

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5688 5689 5690 5691 5692 5693 5694 5696 5697 5698 5699 5700 5701 5702 5703 5704 5705 5706 5707 5708 5709 5710 5711 5712 5713 5714 5715 5716 5717 5718 5719 5720 5721 5722 5723 5724 5725 5726 0H2 H20 Hl H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hl H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H120 Hi H20 H2 H-20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 1120 0H2 H20 Hi H20 H2 H20 2388 2388 2388 2350 2350 2350 2183 2183 2151 2151 2151 2158 2138 2138 2004 2004 2004 2218 2218 2218 2219 2419 2419 20419 2031 2031 2238 2238 2238 2234 2314 2314 234 2430 2430 2438 2398 2398 17.728 24. 700 24.695 25.603 21.387 21. 332 22.351 18.730 19.326 17 .917 20.874 21.747 20.481 20.819 20.456 21.769 -14.161 -8.316 -7 .542 -8.257 -6.900 -6.835 -6.980 -8.591 -8.205 -8.662 -17 .466 -17.302 -16.588 -17.988 -17 .393 -17 .913 17.485 -7.351 17.641 -6.500 16.879 -7.780 20.265 -5.720 20.758 -6.394 19.357 -6.018 17.171 -14.901 16.436 -14.447 16.533 16.116 15.920 9.455 8 .969 9.356 4.225 3 806 4.506 1.652 2.237 1.302 2.709 3 .670 2.613 1.591 2.261 2.128 2.643 3 .056 2 .671 7.921 7.234 7.729 6.433 5 .679 7 .182 7 .540 8.286 7 .600 3 .905 4.811 3 .965 -2.476 -2.629 -1.683 -9 .918 1.00 39.92 1.00 0.00 1.00 0.00 1.00 41.89 1.00 0.00 1.00 0.00 1.00 28.26 1 Art n An 1.00 0.00 1.00100.47 1.00 0.00 1.00 0.00 1.00 8.74 1.00 0.00 1 .00 0.00 1.00 7.03 1.00 0.00 1.00 0.00 1.00 55.49 1.00 0.00 1.00 0.00 1.00 29.43 1.00 0.00 1.00 0.00 1.00 34.49 1.00~ 0.00 1.00 0.00 1.00 52.94 1.00 0.00 1.00 0.00 1.00 40.23 1.00 0.00 1.00 0.00 1.00 39.10 1.00 0.00 1.00 0.00 1.00 3 i. 1.00 0.00 1.00 0.00 19.578 -16.187 18.984 -16.029 18.968 -16.183 23.558 -17.675 23.974 -17.229 23.895 -18.577 23.469 -16.836 23.490 -17.175 24.143 -16.139 24.508 -16.953 23.560 -16.935 24.557 -17.528 31.756 -8.627 31.272 -9.319 -10.392 31.395 -8.751 -9.028 375 ATOM 5727 OH2 H20 2357 ATO 527 0H2H2 257 35.235 -6.559 -13.025 1.00 36.71 ATOM 5728 ATOM 5729 ATOM 5730 ATOM 5731 ATOM 5732 ATOM 5733 ATOM A ATOM 5735 ATOM 5736 ATOM 5737 ATOM 5738 ATOM 5739 ATOM 5740 1 5 ATOM 5741 ATOM 5742 ATOM 5743 ATOM 5744 ATOM 5745 ATOM 5746 ATOM 5747 ATOM 5748 ATOM 5749 ATOM 5750 ATOM 5751 ATOM 5752 ATOM 5753 ATOM 5754 ATOM 5755 ATOM 5756 ATOM 5757 ATOM 5758 ATOM 5759 ATOM 5760 ATOM 5761 ATOM 5762 ATOM 5763 ATOM 5764 ATOM 5765 Hi H2 0H2 Hi H2 0H2 Hi' H2 0H2 Hi H2 0H2 Hi H2 0H2 Hi H2 0H2 Hi H2 0H2 Hi H2 0H2 F-l H2 0H2 Hi H2 0H2 Hi H2 0H2 Hi H2 0H2 Hi H2 H20 H20 H2 0 H2 0 H20 H20 H2 0 H2 0 H2 0 H2 0 H2 0 2357 2357 2096 2096 2096 2386 2386 2386 2401 2401 2401 2112 2112 2112 2099 2099 2099 2368 2368 2368 2377 2377 2377 2424 2424 2424 2023 2023 2023 2155 2155 2155 2040 2040 2040 2034 2034 2034 35.237 35.388 28.378 28. 314 29.306 22.098 22.328 22.946 19.525 19.053 20.414 13.236 12.946 14.149 16. 728 16.632 16.491 16.789 16.718 17.727 29.291 29.956 29.866 34.504 34.199 33.787 15.631 16.126 15.137 27.699 27.056 27.833 21.670 22.395 20.930 27.535 27.066 27.618 -6.279 -12.103 -5 .723 0.965 1. 415 1.134 -15.122 -15. .611 -14.810 -16. 915 -17. 603 -17.217 -6 .440 -5.540 -6 .441 -3 .157 -3 .797 -3 .755 -13.334 -13 .705 -13 .076 -10.210 -10 .411 834 -6.760 -5.886 -7.317 .5 .950 5 .955 5.128 2 .486 3 116 1 .887 7 .029 7 459 7 .613 4 .082 4.295 4 .944 -13 .483 -16.864 -17.728 -16 .635 -27.193 -27.986 -26.865 -19 .140 -18.636 -18.897 -18.191 -18.395 -18.482 -24.065 -23.348 -24.792 -22 .170 -21.278 -22.156 -0.300 -0.974 0.395 -9.490 -9.757 -9.834 -19.680 -18.848 -19.588 -19.359 -19 .697 -20.103 -14.264 -13.806 -14.073 -9.593 -10.404 -9.184 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0 .00 30.28 0.00 0.00 30.97 0.00 0.00 60.66 0.00 0.00 30.00 0.00 0 .00 31.03 0.00 0.00 58.09 0.00 0.00 50.66 0.00 0 .00 27.48 0.00 0.00 12.26 0.00 0 .00 26.98 0 .00 0.00 19.72 0.00 0.00 11.33 0.00 0.00 1.00 0.00

S

376 ATOM 5766 OH2 H20 2146 26.621 3.630 1.891 1.00 30.47 ATOM 5767 HI H20 2146 26.375 3.894 1.000 1.00 0.00 ATOM 5768 H2 H20 2146 25.859 3.131 2.201 1.00 0.00 ATOM 5769 OH2 H20 2068 20.920 3.904 -3.760 1.00 7.73 ATOM 5770 HI H20 2068 20.187 4.266 -4.277 1.00 0.00 ATOM 5771 H2 H20 2068 20.537 3.848 -2.870 1.00 0.00 ATOM 5772 OH2 H20 2364 27.480 -2.239 11.630 1.00 42.03 ATOM 5773 H1 H20 2364 28.335 -2.674 11.627 1.00 0.00 ATOM 5774 H2 H20 2364 27.679 -1.400 11.186 1.00 0.00 ATOM 5775 OH2 H20 2343 24.938 -3.397 12.441 1.00 63.93 ATOM 5776 HI H20 2343 25.826 -3.111 12.155 1.00 0.00 ATOM 5777 H2 H20 2343 24.545 -2.572 12.718 1.00 0.00 ATOM 5778 OH2 H20 2113 20.780 9.545 0.873 1.00 21.71 ATOM 5779 HI H20 2113 21.269 10.305 0.549 1.00 0.00 15 ATOM 5780 H2 H20 2113 21.101 8.844 0.281 1.00 0.00 ATOM 5781 OH2 H20 2045 19.024 5.919 -5.656 1.00 15.08 ATOM 5782 HI H20 2045 18.298 5.988 -6.294 1.00 0.00 ATOM 5783 H2 H20 2045 19.582 6.638 -5.959 1.00 0.00 ATOM 5784 OH2 H20 2054 21.114 5.417 -9.307 1.00 22.18 20 ATOM 5785 HI H20 2054 20.193 5.540 -9.064 1.00 0.00 ATOM 5786 H2 H20 2054 21.468 4.912 -8.570 1.00 0.00 ATOM 5787 OH2 H20 2342 13.713 -6.970 -4.121 1.00 12.52 ATOM 5788 HI H20 2342 14.059 -6.564 -3.321 1.00 0.00 ATOM 5789 H2 H20 2342 13.327 -7.788 -3.792 1.00 0.00 ATOM 5790 OH2 H20 2109 13.864 8.376 -3.158 1.00 12.93 ATOM 5791 H1 H20 2109 14.640 8.635 -2.622 1.00 0.00 ATOM 5792 H2 H20 2109 13.501 7.644 -2.646 1.00 0.00 ATOM 5793 OH2 H20 2098 11.925 3.812 -15.931 1.00 18.96 ATOM 5794 HI H20 2098 11.075 3.560 -16.296 1.00 0.00 ATOM 5795 H2 H20 2098 12.285 4.414 -16.600 1.00 0.00 ATOM 5796 OH2 H20 2365 9.223 -0.496 -14.217 1.00 54.84 ATOM 5797 HI H20 2365 9.824 -1.238 -14.298 1.00 0.00 ATOM 5798 H2 H20 2365 9.151 -0.395 -13.258 1.00 0.00 ATOM 5799 OH2 H20 2404 12.428 8.296 -6.209 1.00 9.63 ATOM 5800 HI H20 2404 13.062 8.041 -5.522 1.00 0.00 ATOM 5801 H2 H20 2404 11.618 8.368 -5.696 1.00 0.00 ATOM 5802 OH2 H20 2156 12.447 8.353 -8.928 1.00 14.17 ATOM 5803 HI H20 2156 12.431 8.321 -7.945 1.00 0.00 ATOM 5804 H2 H20 2156 12.713 9.272 -9.054 1.00 0.00 377 00.

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5805 5806 5807 5808 5809 5810 5811 5812 5813 5814 5815 5816 5817 5818 5819 5820 5821 5822 5823 5824 5825 5826 5827 5828 5829 5830 5831 5832 5833 5834 5835 5836 5837 5838 5839 5840 5841 5842 5843 0H2 H20 81 H20 82 H20 082 H20 Hi H20 H2 H20 082 H20 Hl H20 H2 H20 082 H20 H1 820 H2 820 082 H20 H1 820 82 H20 082 820 H1 H20 H2 820 082 820 H1 820 82 820 082 820 H1 H20 82 820 082 H20 Hl H20 82 H20 082 H20 H1 820 82 820 082 820 H1 820 82 H20 082 820 H1 820 82 820 082 H20 81 820 82 820 2423 2423 2423 2299 2299 2299 2232 2232 2232 2100 2100 2100 2111 2111 2111 2137 2137 2137 2018 2018 2018 2220 2220 2220 2007 2007 2007 2338 2338 2338 2170 2170 2170 2291 2291 2291 2272 2272 2272 11.556 21.534 11.961 21.494 12.201 21.063 16.641 12.291 16.261 13.167 16.480 12.192 53.010 -16.149 52.288 -15t839 52.553 -16.366 57.480 -6.928 57.150 -6.086 56.946 -6.989 54.138 -5.214 53.742 -4.396 53.615 -5.424 48.495 -20.103 48.754 -20.324 47.706 -19.564 41.599 -13.711 42.183 -14.405 41.682 -13.790 39.734 -11.952 39.941 -11.999 40.429 -12.556 38.551 -8.691 38.595 -9.046 39.156 -9.276 39.902 -21.211 40.074 -21.614 40.667 -20.628 37.082 -11.430 37.916 -10.964 36.648 -11.216 35.762 -12.267 35.672 -13.215 36.292 -12.037 39.915 -10.797 39.983 -10.215 40.129 -10.212 9.898 10.776 9.362 5.375 5.230 6.327 14.337 14.896 13.518 18. 196 18.572 17.402 16.024 15.713 16.797 22.150 21. 248 22 .023 26.160 26.481 25.203 27.025 27.961 26.668 27.629 28.528 27.166 23.898 23.041 23.991 19.932 20.031 20.773 17.716 17.815 18.513 17 .685 16.922 18 .420 1.00 47.08 1.00 0.00 1.00 0.00 1.00 46.28 1.00 0.00 1.00 0.00 1.00 24.27 1.00 0.00 1.00 0.00 1.00 40.81 1.00 0.00 1.00 0.0.0 1.00 25.96 1.00 0.00 1.00 0.00 1.00 23.95 1.00 0.00 1.00 0.00 1.00 17.34 1.00 0.00 1.00 0.00 1.00 13.25 1.00 0.00 1.00 0.00 1.00 11.59 1.00 0.00 1.00 0.00 1.00 42.52 1.00 0.00 1.00 0.00 1.00 8.72 1.00 0.00 1.00 0.00 1.00 29.90 1.00 0.00 1.00 0.00 1.00 44.60 1.00 0.00 1.00 0.00 378 ATOM 5844 OH2 H20 2197 43.409 -20.674 28.340 1.00 42.19 ATOM 5845 ATOM 5846 ATOM 5847 ATOM 5848 ATOM 5849 ATOM 5850 ATOM 5851 ATOM 5852 ATOM 5853 ATOM 5854 ATOM 5855 ATOM 5856 ATOM 5857 15 ATOM 5858 ATOM 5859 ATOM 5860 ATOM 5861 ATOM 5862 ATOM 5863 ATOM 5864 ATOM 5865 ATOM 5866 ATOM 5867 ATOM 5868 ATOM 5869 ATOM 5870 ATOM 5871 ATOM 5872 ATOM 5873 ATOM 5874 ATOM 5875 ATOM 5876 ATOM 5877 ATOM 5878 ATOM 5879 ATOM 5880 ATOM 5881 ATOM 5882 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 H1 H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 H1 H20 H2 H20 2197 2197 2121 2121 2121 2407 2407 2407 2359 2359 2359 2391 2391 2391 2047 2047 2047 2055 2055 2055 2006 2006 2006 2438 2438 2438 2354 2354 2354 2308 2308 2308 2420 2420 2420 2185 2185 2185 43.896 -21.187 42.571 -21.155 39.304 -19.820 39.361 -20.164 38.371 -19.897 51.999 -9.716 52.431 -9.793 52.746 -9.752 43.346 -4.177 42.843 -3.822 43.092 -3.596 55.832 -19.332 55.780 -18.633 56.673 -19.147 50.968 -7.693 50.442 -7.529 51.298 -6.818 35.378 -14.080 35.625 -14.970 36.179 -13.577 34.501 -16.131 34.648 -15.191 34.190 -16.133 27.683 28.384 27.794 26.895 27.999 41.121 41.974 40.505 37.568 36.819 38.289 27.628 26.968 28.044 22.248 21.462 22.456 21.765 21.492 21.544 23.435 23.259 24.347 36.075 36.071 36.717 25.879 26.772 25.990 31.374 31.830 31.956 18.893 19.034 18.774 20.364 20.976 20.967 1.00 0.00 1.00 0.00 1.00 27.99 1.00 0.00 1.00 0.00 1.00 70.95 1.00 0.00 1.00 0.00 1.00 42.93 1.00 0.00 1.00 0.00 1.00 23.55 1.00 0.00 1.00 0.00 1.00 96.94 1.00 0.00 1.00 0.00 1.00 19.87 1.00 0.00 1.00 0.00 1.00 11.58 1.00 0.00 1.00 0.00 1.00 31.31 1.00 0.00 1.00 0.00 1.00 29.54 1.00 0.00 1.00 0.00 1.00 21.34 1.00 0.00 1.00 0.00 1.00 37.09 1.00 0.00 1.00 0.00 1.00 48.82 1.00 0.00 1.00 0.00 44.149 43.202 44.191 36.028 35.896 35.939 33.617 34.430 33.358 37.905 38.486 38.528 41.075 40.346 41.785 -6.639 -6.824 -5.912 -4.916 -4.591 -5.866 -4.709 -5.022 -3.976 7.003 6.250 7.722 7.225 7.335 6.958 379 ATOM 5883 OH2 H20 2402 57.143 -2.340 11.369 1.00 27.22

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5884 5885 5886 5887 5888 5889 5890 5891 5892 5893 5894 5895 5896 5897 5898 5899 5900 5901 5902 5903 5904 5905 5906 5907 5908 5909 5910 5911 5912 5913 5914 5915 5916 5917 5918 5919 5920 5921 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 H1 H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 2402 2402 2090 2090 2090 2214 2214 2214 2180 2180 2180 2208 2208 2208 2033 2033 2033 2160 2160 2160 2194 2194 2194 2370 2370 2370 2136 2136 2136 2030 2030 2030 2412 2412 2412 2089 2089 2089 57.652 -1.628 56.387 -1.842 58.792 -4.704 59.176 -4.804 59.358 -5.288 61.585 1.744 60.908 1.086 61.115 2.206 47.497 -23.533 48.118 -24.053 47.939 -22.672 45.577 -25.548 44.707 -25.952 46.149 -26.159 24.690 -14.893 25.308 -15.101 24.598 -13.934 30.810 -9.362 31.326 -8.858 30.705 -10.213 31.416 -15.610 31.229 -16.277 32.035 -15.023 31.999 -15.570 32.407 -16.359 31.786 -15.803 29.123 -28.115 29.011 -28.804 28.613 -27.383 23.452 -11.832 22.530 -11.594 23.864 -10.993 20.673 -7.099 20.237 -7.012 20.180 -6.433 15.819 -22.003 15.795 -22.742 16.771 -21.953 11.759 10.998 21.220 22.105 20.706 22.791 22.576 23.499 21.262 20.714 21.265 24.777 24.684 24.313 21.736 21.006 21.584 1.806 2.443 2.259 7.447 6.772 7.010 12.535 12.895 11.629 11.438 10.776 11.083 22.557 22.374 22.317 20.940 21.808 20.446 23.299 22.683 23.470 1.00 0.00 1.00 0.00 1.00 45.35 1.00 0.00 1.00 0.00 1.00 66.01 1.00 0.00 1.00 0.00 1.00 19.46 1.00 0.00 1.00 0.00 1.00 34.69 1.00 0.00 1.00 0.00 1.00 5.32 1.00 0.00 1.00 0.00 1.00 63.50 1.00 0.00 1.00 0.00 1.00 65.23 1.00 0.00 1.00 0.00 1.00 24.67 1.00 0.00 1.00 0.00 1.00 35.74 1.00 0.00 1.00 0.00 1.00 10.50 1.00 0.00 1.00 0.00 1.00 56.26 1.00 0.00 1.00 0.00 1.00 35.26 1.00 0.00 1.00 0.00 380 ATOM 5922 0H2 H120 2072 11.320 -15.295 3292 10 2.4 32.192 1.00 20.48

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

5923 5924 5925 5926 5927 5928 5929 5930 ATOM 5931 ATOM 5932 ATOM 5933 ATOM 5934 ATOM 5935 15 ATOM 5936 ATOM 5937 ATOM 5938 ATOM 5939 ATOM 5940 ATOM 5941 ATOM 5942 ATOM 5943 ATOM 5944 ATOM 5945 ATOM 5946 ATOM 5947 ATOM 5948 ATOM 5949 ATOM 5950 ATOM 5951 ATOM 5952 ATOM 5953 ATOM 5954 ATOM 5955 ATOM 5956 ATOM 5957 ATOM 5958 ATOM 5959 ATOM 5960 Hl H120 H12 H20 0P12 H20 H1 H20 H2 H120 0H2 H120 Hi H20~ H12 H20 082 H120 Hl1 H20 H2 H120 012 P120 Hi H120 H2 P120 0H2 H120 Hl H120 H2 P120 0P12 H20 Hl H120 P12 H20 082 H120 Hi P120 H2 P120 0P12 H20 Hl H120 P12 P120 012 P120 Hl P120 H2 P120 082 P120 Hl P120 P12 H20 012 P120 Hl P120 P12 P120 012 P120 Hl P120 H2 P120 2072 2072 2316 2316 2316 2399 2399 2399 2192 2192 2192 2231 2231 2231 2161 2161 2161 2140 2140 2140 2246 2246 2246 2440 2440 2440 2331 2331 2331 2070 2070 2070 2271 2271 2271 2379 2379 2379 11.654 -15.091 11.384 -16.258 10.042 -12.494 10.406 -13.370 10.289 -12.453 8.603 -14.948 8.313 -14.487 8.473 -14.262 7.916 -13.636 7.104 -13.217 8.601 -13.075 8.067 -13.460 8.632 -14.192 7.984 -12.955 16.836 -33.080 16.968 -33.045 17.012 -32.166 26.971 -29.009 26.721 -29.930 27.184 -28.985 23.752 -26.455 24.151 -27.078 23.459 -27.079 13.303 -10.401 13.963 -10.537 12.478 -10.553 15.775 -24.807 16.212 -25.108 16.323 -24.056 15.042 -18.872 15.952 -18.620 14.605 -18.849 17.717 -14.518 17.672 -14.366 17.046 -15.189 25.821 -12.138 26.013 -11.483 25.466 -11.558 31. 308 32.186 33.237 32.999 34. 164 35.233 36.053 34. 569 37.451 37.761 37.836 23.591 23.328 22.777 34.391 35.343 34.136 44.630 44.498 45.569 45.524 46.149 44.834 26.635 27.326 27.125 48.886 48.074 49.119 44.584 44.779 45.437 46.249 45.294 46.389 44. 278 43.596 44.966 1.00 0.00 1.00 0.00 1.00 24.17 1.00 0.00 1.00 0.00 1.00 23.99 1.00 0.00 1.00 0.00 1.00 70.33 1.00 0.00 1.00 0.00 1.00 38.21 1.00 0.00 1.00 0.00 1.00 54.29 1.00 0.00 1.00 0.00 1.00 9.87 1.00 0.00 1.00 0.00 1.00 8.02 1.00 0.00 1.00 0.00 1.00 52.80 1.00 0.00 1.00 0.00 1.00 17.34 1.00 0.00 1.00 0.00 1.00 18.63 1.00 0.00 1.00 0.00 1.00 47.83 1.00 0.00 1.00 0.00 1.00 32.22 1.00 0.00 1.00 0.00 381

C

9* C 9 *9*C 9

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

5961 5962 5963 5964 5965 5966 5967 5968 5969 5970 5971.

5972 5973 5974 5975 5976 5977 5978 5979 5980 5981 5982 5983 5984 5985 5986 5987 5988 5989 5990 5991 5992 5993 5994 5995 5996 5997 5998 5999 0H2 H20 Hl H20 H2 H20 0H2 H20 Hl H20 H2 H20 0H2 H20 Hl H20 H2 H20 0H2 H20 Hl H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 HZ0 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0E2 H20 Hi H20 H2 H20 0H2 H2 0 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 2108 2108 2108 2328 2328 2328 2425 2425 2425 2205 2205 2205 2362 2362 2362 2061 2061 2061 2119 2119 2119 2348 2348 2348 2312 2312 2312 2344 2344 2344 2333 2333 2333 2077 2077 2077 2172 2172 2172 20.565 21.504 20.219 24.406 23 .863 25 .189 21.666 21.213 20.930 21.184 20.516 20 .771 19 .416 20.154 18.683 24.677 24.757 24.437 27.988 28.536 28.598 32.711 32.068 33.008 32.395 31.958 31.799 33 .317 34 .118 32 .652 35.576 35.635 35.578 -8 .761 -8.707 -8 .866 -6 .118 -5.355 -5 .982 -3.377 -3.720 -3 .079 -1.374 -1.305 -1.991 -1.273 -0.939 -1.148 1.554 0.836 2.296 -8.763 -8.635 -9.196 -3.156 -3.312 -4 .037 -3 .078 -3 .871 -2.392 0.119 -0 .155 -0.479 -5.496 -6.428 -5 .071 39.099 39.314 39.994 40.654 40.422 40.110 40.429 41. 201 39.862 23.368 24.082 22.764 25.451 25.985 26.064 32.306 32 .940 32.864 33 .829 33.040 34.463 40 .465 39.768 40.705 33 .580 33.911 33 .903 30.693 31.142 31.039 33.034 33 .271 33 .898 26.976 26.459 27 .622 28.985 28.305 29.710 1.00 2.25 1.00 0.00 1.00~ 0.00 1.00 14.45 1.00 0.00 1.00 0.00 1.00 52.73 1.00 0.00 1.00 0.00 1.00 17.33 1.00 0.00 1.00 0.00 1.00 28.10 1.00 0.00 1.00 0.00 1.00 11.86 1.00 0.00 1.00 0.00 1.00 17.60 1.00 0.00 1.00 0.00 1.00 16.04 1.00 0.00 1.00 0.00 1.00 31.42 1.00 0.00 1.00 0.00 1.00 56.56 1.00 0.00 1.00 0.00 1.00 18.08 1.00 0.00 1.00 0.00 1.00 20.62 1.00 0.00 1.00 0.00 1.00 30.56 1.00 0.00 1.00 0.00 C C S. C

C

*9CC*C

C

33.384 -15.305 33.638 -14.532 32.779 -14.932 26.897 -25.114 27.153 -24.490 27.491 -24.907 382 9@S@ 4 @0 0S S

OS@*

S

4560 0 0 *000 @0 0 *500 *0 0 0 000 S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

6000 6001 6002 6003 6004 6005 6006 6007 6008 6009 6010 6011 6012 6013 6014 6015 6016 6017 6018 6019 6020 6021 6022 6023 6024 6025 6026 6027 6028 6029 6030 6031 6032 6033 6034 6035 6036 6037 6038 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi 820 82 H20 0H2 820 H1 820 H2 H20 082 H20 Hi 820 82 820 082 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 820 Hi H20 H2 H20 082 H20 Hi 820 H2 H20 0H2 H20 Hi H20 H2 H20 082 820 HI H20 82 H20 082 820 Hi 820 H2 820 082 820 H1 820 82 820 2446 2446 2446 2433 2433 2433 2067 2067 2067 2321 2321 2321 2062 2062 2062 2120 2120 2120 2154 2154 2154 2249 2249 2249 2300 2300 2300 2204 2204 2204 2288 2288 2288 2141 2141 2141 2101 2101 2101 44.010 -15.901 44.830 -15.428 44.123 -16.235 38.438 -17.405 39.273 -17.807 37.797 -17.920 29.531 -9.895 29.864 -9.637 29.434 -10.847 35.644 -17.632 35.574 -18.582 36.571 -17.459 24.202 -17.470 24.163 -18.245 25.140.-17.311 13.699 -5.868 14.554 -6.277 13.728 -5.092 9.242 -14.997 9.669 -14.959 9.793 -15.603 25.464 -8.982 25.372 -8.692 25.631 -8.176 29.028 -2.245 29.282 -3.175 28.487 -2.123 33.950 -9.271 33.742 -9.522 33.127 -9.462 40.485 -9.257 41.241 -9.027 40.854 -9.285 40.365 -14.937 40.009 -14.090 39.970 -15.022 45.271 6.055 45.897 6.745 45.071 5.698 36.613 36.448 37 .506 38.176 37.928 37.666 35.716 36.590 35.846 40. 417 40.274 40.197 37.624 37.065 37.751 38.824 39.001 39.392 28.355 27 .498 28.854 47 .160 48 .068 46.668 34.431 34.367 33.650 48.503 49.406 48.040 37.985 37.430 38.872 30.859 31.144 29.984 35.780 35.495 34.903 1.00 37.57 1.00 0.00 1.00 0.00 1.00 48.29 1.00 0.00 1.00 0.00 1.00 14.12 1.00 0.00 1.00 0.00 1.00 20.37 1.00 0.00 1.00 0.00 1.00 45.80 1.00 0.00 1.00 0.00 1.00 30.28 1.00 0.00 1.00 0.00 1.00 24.97 1.00 0.00 1.00 0.00 1.00 21.25 1.00 0.00 1.00 0.00 1.00 41.04 1.00 0.00 1.00 0.00 1.00 28.17 1.00 0.00 1.00 0.00 1.00 13.77 1.00 0.00 1.00 0.00 1.00 20.91 1.00 0.00 1.00 0.00 1.00 63.28 1.00 0.00 1.00 0.00 to 0 *see 0* 0 383 ATOM 6039 OH2 H20 2010 32.554 4.915 -4.911 1.00 28.06 ATOM 6040 ATOM 6041 ATOM 6042 ATOM 6043 ATOM 6044 ATOM 6045 ATOM 6046 ATOM 6047 1 0 ATOM 6048 ATOM 6049 ATOM 6050 ATOM 6051 ATOM 6052 ATOM 6053 ATOM 6054 ATOM 6055 ATOM 6056 ATOM 6057 20 ATOM 6058 ATOM 6059 ATOM 6060 ATOM 6061 ATOM 6062 ATOM 6063 ATOM 6064 ATOM 6065 ATOM 6066 ATOM 6067 ATOM 6068 ATOM 6069 ATOM 6070 ATOM 6071 ATOM 6072 ATOM 6073 ATOM 6074 ATOM 6075 ATOM 6076 ATOM 6077 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 H1 H20 H2 H20 OH2 H20 Hi H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 H1 H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 HI H20 H2 H20 OH2 H20 H1 H20 H2 H20 OH2 H20 HI H20 H2 H20 2010 2010 2015 2015 2015 3191 3191 3191 3147 3147 3147 3098 3098 3098 3156 3156 3156 3104 3104 3104 3212 3212 3212 3181 3181 3181 3019 3019 3019 3178 3178 3178 3141 3141 3141 3125 3125 3125 -3.078 -3.469 -3.834 8.060 8.121 8.142 5.207 4.246 5.523 2.425 1.889 1.733 9.654 9.692 10.346 15.589 14.759 16.112 -3.743 -2.961 -4.400 -4.806 -4.368 -5.295 -5.835 -5.525 -5.630 31.801 31.519 32.479 -4.252 -3.684 -4.669 -4.377 -4.590 -5.258 8.717 8.849 8.644 9.047 8.446 9.656 2.444 3.402 2.182 9.732 10.169 10.516 1.638 1.156 1.099 -0.424 -1.251 -0.744 -1.383 -2.113 -0.630 -27.442 -27.882 -28.053 32.927 5.785 32.828 4.445 21.877 -20.746 22.711 -20.839 22.034 -21.259 -4.780 -4.101 49.067 49.547 48.267 10.967 11.636 10.551 9.828 10.768 9.435 -7.692 -7.841 -8.595 -8.391 -8.916 -8.061 -4.630 -4.681 -5.249 -1.575 -1.343 -1.784 1.512 1.243 1.016 0.257 0.014 1.049 2.620 3.165 3.204 2.541 1.730 2.863 11.397 11.830 11.618 1.00 0.00 1.00 0.00 1.00 8.80 1.00 0.00 1.00 0.00 1.00 16.19 1.00 0.00 1.00 0.00 1.00 16.74 1.00 0.00 1.00 0.00 1.00 30.64 1.00 0.00 1.00 0.00 1.00 29.49 1.00 0.00 1.00 0.00 1.00 38.50 1.00 0.00 1.00 0.00 1.00 19.23 1.00 0.00 1.00 0.00 1.00 27.00 1.00 0.00 1.00 0.00 1.00 26.95 1.00 0.00 1.00 0.00 1.00 25.81 1.00 0.00 1.00 0.00 1.00 42.64 1.00 0.00 1.00 0.00 1.00 42.53 1.00 0.00 1.00 0.00 0.814 26.814 0.885 27.670 -0.088 26.558 384 ATOM 6078 OH2 H20 3013 ATM 07 02 2O303 8.353 -1.014 13.721 1.00 39.02

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

6079 6080 6081 6082 6083 6084 6086 6087 6088 6089 6090 6091 6092 6093 6094 6095 6096 6097 6098 6099 6100 6101 6102 610 3 6104 6105 6106 6107 6108 6109 6110 6111 6112 61113 6114 6115 6116 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hl H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 Hi H20 H2 H20 0H2 H20 HI H20 H2 H20 0H2 H20 Hi H20 H2 H20 3013 3013 3029 3029 3029 3064 3064 3064 3090 3090 3090 3199 3199 3199 3058 3058 3058 3223 3223 3223 3194 3194 3194 3137 3137 3137 3108 3108 3108 3091 3091 3091 3017 3017 3017 3117 3117 3117 9.135 7.943 16. 903 16. 700 16.844 8.191 8.643 7.835 -2.265 -2.320 -3.039 17.013 17.299 17.836 19.287 19.593 19.775 -9.812 -9.918 -10. 701 24.050 23.909 23.458 18.552 19.371 18.856 22. 639 22.763 23.235 56.601 57.268 56.163 47.313 48.025 46.553 36.098 35.588 35.861 -0.527 -1.259 3 .887 3.026 3.720 20.675 2164 19.914 27.363 26.647 27.231 1.765 1.776 1.578 -2.958 -3.850 -2.798 -0.517 0.387 -0.862 -18.614 -19.568 -18.365 -14.358 -13.903 -15.295 14.497 14 .199 13 .880 -4.492 -4.523 -3.659 -10.322 -10.044 -10.276 1.714 0.898 2.135 13.410 12.884 5.300 5.691 4.351 1.300 0.604 0.829 13.784 14. 421 13.231 10.108 11.032 9.644 9.801 10.036 8.991 10.459 10.100 10.362 -0.304 -0.359 0.415 -19.355 -19.578 -19.328 -11.334 -12.248 -10.879 19.249 19.963 19.474 26.171 25.576 25.584 21.377 21. 398 22.207 1.00 0.00 1.00 0.00 1.00 15.87 1.00 0.00 1.00 0.00 1.00 33.79 1.00 0.00 1.00 0.00 1.00 57.66 1.00 0.00 1.00 0.00 1.00 33.28 1.00 0.00 1.00 0.00 1.00 35.84 1.00 0.00 1.00 0.00 1.00 66.07 1.00 0.00 1.00 0.00 1.00 32.20 1.00 0.00 1.00 0.00 1.00 64.23 1.00 0.00 1.00 0.00 1.00 51.77 1.00 0.00 1.00 0.00 1.00 48.51 1.00 0.00 1.00 0.00 1.00102 .08 1.00 0.00 1.00 0.00 1.00 39.42 1.00 0.00 1.00 0.00 385

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

END

6117 6118 6119 6120 6121 6122 6123 6124 6125 6126 6127 6128 6129 6130 6131 6132 6133 6134 0H2 H20 Hl H20 H2 H20 0112 H20 Hl H120 H12 H20 0112 H20 Hi H120 H2 1120 0112 H20 Hi H20 H12 H20 0112 H20 Hi H20 H2 1120 0H2 H20 Hi H120 H2 H20 3200 3200 3200 3040 3040 3040 3047 3047 3047 3061 3061 3061 3206 3206 3206 3045 3045 3045 9 862 19 .643 9.445 -19.512 9.166 -19.458 28.246 -22.043 29.090 -22.212 28.110 -21.103 32.378 -20.251 32,631 -19.373 32.745 -20.828 26.628 -27.624 25.753 -27.319 27.210 -27.114 15.002 -7.120 14.082 -7.406 15.150 -6.557 41.800 -16.544 40.959 -16.083 42-155 -16.453 45.852 44.999 46.485 26.268 25 .842 26.103 42.121 42.435 42.799 38.628 38.895 39.215 42.223 42.327 42.986 33.852 33.908 34.748 1.00 43.84 1.00 0.00 1.00 0.00 1.00 21.05 1.00 0.00 1.00 0.00 1.00 20.98 1.00 0.00 1.00 0.00 1.00 16.19 1.00 0.00 1.00 0.00 1.00 29.38 1.00 0.00 1.00 0.00 1.00 33.08 1.00 0.00 1.00 0.00 a

C

*Note: See copyright notice on page 1.

386 Appendix IV: Coordinates for the 3D structure of SY-C:peptide complex created by user: 1 N THR ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

HN

CA

HA

CB

HB

OGI

HGI

CG2 HG21 HG22 HG23

C

0 CT2 HT21 HT2 2 HT2 3

CNT

ONT

N

HN

CA

HA

CB

HB1 HB2

CG

CDI

HD1

CEI

HE1 CD2

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

PTYR

PTYR

PTYR

PTYR

PTYR

PTYR

PTYR

PTYR

PTYR

PTYR

PTYR

PTYR

PTYR

dave 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 2 2 2 4.888 4.897 5.664 6.160 6.679 6.327 7.908 8.091 6.889 6.764 7 .885 6.165 4.724 4.484 3.263 2.897 3.830 2.412 4.150 4.157 4.187 4.382 3.272 3 .596 1.861 1.549 1.151 1.861 1.804 1.650 1.984 1.976 2.091 2.160 9.383 8.671 9.239 10.195 8.116 7.446 8.651 8.269 7.323 7.967 6.893 6 .511 8.926 7.776 10.438 9.423 10.744 11.106 10.492 11.458 10.014 10.915 9.812 8.897 9.638 10.512 9.496 8.447 7.154 7.036 6.023 5.051 8.598 9 .584 9.370 10.072 8.157 7.974 8.338 9.117 8.766 9.614 7.048 6.175 7.012 6.970 6.998 6.650 10.767 10.918 11.645 10.644 9.528 8.775 6.438 6.792 5.331 4 .834 5 .864 6.435 5 .049 6.740 6.171 5.110 6.974 6.522 8.127 8.557 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.25 1.30 1.17 1.22 1.23 1.29 1.37 1.72 1.13 1.37 1.59 1.49 1.00 0.99 1.39 1.48 1.89 1.82 1.28 1.27 0.94 1.03 0.82 0.77 0.82 0.91 0.76 0.84 0.75 0.67 0.82 0.78 1.00 1.09

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

ATOM 19 25 ATOM 20 ATOM 21 ATOM 22 ATOM 23 ATOM 24 ATOM 25 ATOM 26 ATOM 27 ATOM 28 ATOM 29 ATOM 30 ATOM 31 ATOM 32 ATOM 33 ATOM 34 HD2 PTYR 2 387

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

35 CE2 PTYR 2 36 HE2 PTYR 2 37 CZ PTYR 2 38 OH PTYR 2 39 P04 PTYR 2 40 OCI PTYR 2 41 OC2 PTYR 2 4* 22 OT 2 43 C PTYR 2 44 0 PTYR 2 45 N GLU 3 46 HN GLU 3 47 CA GLU 3 48 HA GLU 3 49 CB GLU 3 50 HB1 GLU 3 51 HB2 GLU 3 52 CG GLU 3 53 HGI GLU 3 54 HG2 GLU 3 55 CD GLU 3 56 OE1 GLU 3 57 OE2 GLU 3 58 C GLU 3 59 o GLU 3 60 N THR 4 61 HN THR 4 62 CA THR 4 63 HA THR 4 64 CB THR 4 65 HB THR 4 66 OGI THR 4 67 HG1 THR 4 68 CG2 THR 4 69 HG21 THR 4 70 HG22 THR 4 71 HG23 THR 4 72 C THR 4 73 0 THR 4 2.506 2.218 2.396 2.748 1.375 3.442 3 .609 3.336 2.857 3 .965 4.351 4.074 4.702 4.684 4.092 4.669 6.115 6.134 6.666 6.811 7.497 6.658 2.683 1.683 2.676 3 .522 1.393 0.670 1.459 0.752 2.741 2.614 1.145 1.866 0.151 1.176 0.969 1.550 7.601 6.185 5.057 3.685 3.038 2.874 3.836 10.946 12.052 10.574 9.647 11.530 12.335 10.868 10.004 11.558 10 .435 9.445 10.389 11.423 12.317 11. 284 12.066 11.545 13.136 13.511 13.722 13.269 15.232 15.698 15.694 16.446 15.651 15.224 15.313 16.735 13.357 13.759 9.977 8.359 9.180 8.518 8.201 9.642 7.299 4.334 4.556 3.218 3.139 2.143 2.480 0.932 0.646 0.089 1.220 1.669 0.306 2.161 1.671 3 .374 1.850 2.327 1. 047 0.673 0.739 1.432 0.916 0.241 0.561 -0.002 2.353 3.049 2.647 2.458 -0.668 -1.668 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.20 0.97 1.07 1.77 2.43 2.32 2.72 0.81 0.95 0.77 0.83 0.78 0.88 0.74 0.73 0.82 0.91 1.30 1.26 1.64 2.20 2.38 0.76 0.74 0.80 0.86 0.78 0.75 0.90 1.28 1.59 2.03 1.71 2.14 2.33 2.26 0.72 0.77

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

PEP

2.275 7.471 8.938 1.00 1.06 PEP 388 ATOM 74 N LEU 5 -0.094 12.553 -0.635 1.00 0.65 PEP ATOM 75 HN LEU 5 -0.485 12.282 0.242 1.00 0.67 PEP ATOM 76 HA LEU 5 0.126 11.614 -2.443 1.00 0.63 PEP ATOM 77 CB LEU 5 -1.709 11.032 -1.462 1.00 0.59 PEP ATOM 78 HB1 LEU 5 -1.792 10.968 -0.376 1.00 0.64 PEP ATOM 79 HB2 LEU 5 -2.682 11.326 -1.842 1.00 0.68 PEP ATOM 80 CG LEU 5 -1.318 9.692 -2.026 1.00 0.46 PEP ATOM 81o HG LEU 5 -0.240 9.683 166 1.00 0.52 PEP ATOM 82 CD1 LEU 5 -1.705 8.560 -1.097 1.00 0.42 PEP ATOM 83 HD11 LEU 5 -2.721 8.227 -1.304 1.00 1.11 PEP ATOM 84 HD12 LEU 5 -1.037 7.710 -1.230 1.00 1.12 PEP ATOM 85 HD13 LEU 5 -1.654 8.878 -0.060 1.00 1.10 PEP ATOM 86 CD2 LEU 5 -1.988 9.514 -3.356 1.00 0.52 PEP ATOM 87 HD21 LEU 5 -2.029 10.457 -3.888 1.00 1.11 PEP 15 ATOM 88 HD22 LEU 5 -1.451 8.810 -3.959 1.00 1.26 PEP ATOM 89 HD23 LEU 5 -3.002 9.149 -3.225 1.00 1.00 PEP ATOM 90 C LEU 5 -1.322 13.231 -2.604 1.00 0.72 PEP ATOM 91 0 LEU 5 -2.536 13.382 -2.640 1.00 1.31 PEP ATOM 92 NCT LEU 5 -0.427 14.037 -3.203 1.00 1.13 PEP 20 ATOM 93 HCT1 LEU 5 0.554 13.850 -3.136 1.00 1.72 PEP ATOM 94 HCT2 LEU 5 -0.727 14.836 -3.724 1.00 1.61 PEP ATOM 95 CA LEU 5 -0.675 12.071 -1.845 1.00 0.63 PEP ATOM 96 N GLY 1 -21.702 -18.923 0.217 1.00 11.53 ACSY ATOM 97 HT1 GLY 1 -21.532 -19.938 0.069 1.00 11.78 ACSY 25 ATOM 98 HT2 GLY 1 -21.935 -18.753 1.216 1.00 11.73 ACSY ATOM 99 HT3 GLY 1 -22.495 -18.614 -0.381 1.00 11.61 ACSY ATOM 100 CA GLY 1 -20.504 -18.172 -0.138 1.00 11.06 ACSY ATOM 101 HA1 GLY 1 -20.709 -17.110 0.000 1.00 11.33 ACSY ATOM 102 HA2 GLY 1 -20.287 -18.347 -1.191 1.00 11.13 ACSY ATOM 103 C GLY 1 -19.296 -18.576 0.710 1.00 10.41 ACSY ATOM 104 0 GLY 1 -18.259 -18.988 0.205 1.00 10.65 ACSY ATOM 105 N SER 2 -19.508 -18.427 2.030 1.00 9.79 ACSY ATOM 106 HN SER 2 -20.383 -18.084 2.371 1.00 9.80 ACSY ATOM 107 CA SER 2 -18.439 -18.776 2.950 1.00 9.36 ACSY ATOM 108 HA SER 2 -18.713 -18.382 3.932 1.00 9.73 ACSY ATOM 109 CB SER 2 -18.285 -20.294 2.997 1.00 9.43 ACSY ATOM 110 HB1 SER 2 -17.509 -20.584 3.707 1.00 9.49 ACSY ATOM 111 HB2 SER 2 -19.216 -20.770 3.304 1.00 9.38 ACSY ATOM 112 OG SER 2 -17.932 -20.796 1.734 1.00 9.82 ACSY 389 15 2 2 2 2 2 2 ATOM 113 ATOM 114 ATOM 115 ATOM 116 ATOM 117 ATOM 118 ATOM 119 ATOM 120 ATOM 121 ATOM 122 ATOM 123 ATOM 124 ATOM 125 ATOM 126 ATOM 127 ATOM 128 ATOM 129 ATOM 130 ATOM 131 ATOM 132 ATOM 133 ATOM 134 ATOM 135 ATOM 136 ATOM 137 ATOM 138 ATOM 139 ATOM 140 ATOM 141 ATOM 142 ATOM 143 ATOM 144 ATOM 145 ATOM 146 ATOM 147 ATOM 148 ATOM 149 ATOM 150

HN

CA

HA

CB

HB1 HB2

CG

HG1 HG2

CD

HD1 HD2

NE

HE

CZ

NH1 HH11 HH12 NH2 HH21 HH22

C

O0

N

RN

CA

HA

CB

HB1 HB2

CG

HG1 HG2

CD

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

-17.651 -15.762 -14.911 -15.827 -15.054 -15.616 -17.196 -17.381 -17.973 -17.293 -18.320 -16.924 -16.493 -16.896 -15.197 -14.447 -14.846 -13.485 -14.663 -15.225 -13.701 -15.624 -15.148 -16.064 -16.437 -15.985 -16.530 -14.520 -14.059 -13.980 -14.380 -14.567 -15.138 -12.993 HG SER C SER O SER N ARG -17.058 -21.152 -17.138 -18.119 -16.353 -18.690 -16.966 -16.884 -16.480 -16.148 -16.807 -15.760 -15.025 -16.634 -15.193 -14.282 -15.903 -14.895 -14.681 -15.723 -13.729 -12.814 -13.899 -12.843 -11.927 -12.967 -15.118 -15.913 -15.239 -14.897 -13.857 -15.073 -15.953 -13.957 -14.246 -13.668 -14.556 -13.448 -12.495 -11.560 -12.575 -12.456 1.816 2.492 1.743 2.995 3.602 2.637 2.821 1 ir 1.166 0.947 0.549 0.797 1.366 1.079 -0.696 -0.993 -1.297 -1.032 -1.019 -1.359 -1.665 -1.652 -1.907 -1.378 -1.149 -1.621 3.514 3.076 4.776 5.067 5.703 6.606 6.024 6.455 5.104 6.996 6.470 7.775 7.637 6.888 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 9.92 8.68 8.72 8.32 8.52 7.90 8.17 8.2 8.76 8.65 9.04 9.17 9.09 9.72 9.94 9.31 10.34 10.40 11.04 11.79 11.84 12.39 11.17 10.74 11.80 6.86 6.84 6.28 6.63 5.44 5.54 5.41 5.79 5.72 5.07 5.15 5.27 5.03 5.01

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

4 ATOM 151 HD1 ARG 4 -12.207 -12.345 390 ATOM 152 HD2 ARG 4 -12.794 -13.352 8.221 1.00 5.05 ACSY ATOM 153 NE ARG 4 -12.894 -11.325 8.543 1.00 5.65 ACSY ATOM 154 HE ARG 4 -13.490 -10.530 8.432 1.00 6.04 ACSY ATOM 155 CZ ARG 4 -11.987 -11.367 9.537 1.00 6.06 ACSY ATOM 156 NH1 ARG 4 -11.882 -10.345 10.382 1.00 6.93 ACSY ATOM 157 HH11 ARG 4 -12.476 -9.547 10.277 1.00 7.26 ACSY ATOM 158 HH12 ARG 4 -11.209 -10.374 11.121 1.00 7.42 ACSY ATOM 159 NH2 ARG 4 -11.195 -12.428 9.677 1.00 5.95 ACSY ATOM 160 HH21 ARG 4 -11.273 -13.197 9.043 1.00 5.52 ACSY ATOM 161 HH22 ARG 4 -10.523 -12.456 10.417 1.00 6.51 ACSY ATOM 162 C ARG 4 -16.656 -12.730 5.086 1.00 5.05 ACSY ATOM 163 0 ARG 4 -16.958 -12.683 3.900 1.00 5.27 ACSY ATOM 164 N ALA 5 -16.875 -11.746 5.977 1.00 4.86 ACSY o ATOM 165 HN ALA 5 -16.613 -11.857 6.934 1.00 5.05 ACSY 15 ATOM 166 CA ALA 5 -17.506 -10.521 5.519 1.00 4.79 ACSY ATOM 167 HA ALA 5 -18.191 -10.793 4.713 1.00 5.29 ACSY ATOM 168 CB ALA 5 -18.263 -9.875 6.678 1.00 5.32 ACSY ATOM 169 HB1 ALA 5 -18.761 -8.960 6.355 1.00 5.57 ACSY ATOM 170 HB2 ALA 5 -19.023 -10.550 7.071 1.00 5.59 ACSY 20 ATOM 171 HB3 ALA 5 -17.585 -9.619 7.492 1.00 5.61 ACSY ATOM 172 C ALA 5 -16.439 -9.573 4.968 1.00 3.98 ACSY ATOM 173 0 ALA 5 -16.103 -9.594 3.790 1.00 4.06 ACSY ATOM 174 N SER 6 -15.935 -8.743 5.899 1.00 3.66 ACSY ATOM 175 HN SER 6 -16.257 -8.782 6.844 1.00 4.09 ACSY 25 ATOM 176 CA SER 6 -14.912 -7.790 5.500 1.00 3.17 ACSY ATOM 177 HA SER 6 -15.261 -7.303 4.586 1.00 3.31 ACSY ATOM 178 CB SER 6 -14.706 -6.768 6.615 1.00 3.61 ACSY ATOM 179 HB1 SER 6 -13.988 -6.005 6.314 1.00 3.90 ACSY ATOM 180 HB2 SER 6 -15.643 -6.268 6.863 1.00 3.95 ACSY ATOM 181 OG SER 6 -14.221 -7.391 7.777 1.00 4.03 ACSY ATOM 182 HG SER 6 -13.626 -6.778 8.187 1.00 4.34 ACSY ATOM 183 C SER 6 -13.610 -8.534 5.207 1.00 2.86 ACSY ATOM 184 0 SER 6 -13.354 -9.618 5.717 1.00 3.29 ACSY ATOM 185 N VAL 7 -12.810 -7.873 4.350 1.00 2.60 ACSY ATOM 186 HN VAL 7 -13.088 -6.990 3.973 1.00 2.58 ACSY ATOM 187 CA VAL 7 -11.537 -8.470 3.983 1.00 2.97 ACSY ATOM 188 HA VAL 7 -11.748 -9.286 3.286 1.00 3.40 ACSY ATOM 189 CB VAL 7 -10.652 -7.413 3.328 1.00 3.63 ACSY ATOM 190 HB VAL 7 -11.128 -7.090 2.401 1.00 3.85 ACSY 391 ATOM 191 CG1 VAL 7 -10.501 -6.199 4.243 1.00 3.87

ACSY

ATOM 192 HG11 VAL 7 -10.042 -6.480 5.191 1.00 4.23 ACSY ATOM 193 HG12 VAL 7 -11.471 -5.751 4.459 1.00 4.18 ACSY ATOM 194 HG13 VAL 7 -9.874 -5.437 3.779 1.00 3.99 ACSY ATOM 195 CG2 VAL 7 -9.279 -8.000 2.997 1.00 4.53 ACSY ATOM 196 HG21 VAL 7 -8.800 -8.397 3.892 1.00 5.05 ACSY ATOM 197 HG22 VAL 7 -9.366 -8.811 2.273 1.00 4.84 ACSY ATOM 198 HG23 VAL 7 -8.623 -7.239 2.573 1.00 4.79 ACSY ATOM 199 C VAL 7 -10.858 -9.039 5.229 1.00 2.97 ACSY ATOM 200 0 VAL 7 -10.543 -8.329 6.176 1.00 3.56 ACSY ATOM 201 N GLY 8 -10.659 -10.367 5.157 1.00 2.78 ACSY ATOM 202 HN GLY 8 -10.943 -10.882 4.349 1.00 2.72 ACSY ATOM 203 CA GLY 8 -10.020 -11.034 6.274 1.00 3.21 ACSY o ATOM 204 HA1 GLY 8 -10.329 -12.080 6.256 1.00 3.70 ACSY 15 ATOM 205 HA2 GLY 8 -10.383 -10.568 7.190 1.00 3.50 ACSY O ATOM 206 C GLY 8 -8.498 -10.921 6.180 1.00 3.25 ACSY •oATOM 207 0 GLY 8 -7.769 -11.903 6.258 1.00 3.70 ACSY ATOM 208 N SER 9 -8.075 -9.656 6.006 1.00 3.25 ACSY •°"ATOM 209 HN SER 9 -8.730 -8.902 5.954 1.00 3.31 ACSY 20 ATOM 210 CA SER 9 -6.649 -9.410 5.899 1.00 3.63 ACSY ATOM 211 HA SER 9 -6.521 -8.404 5.489 1.00 3.96 ACSY ATOM 212 CB SER 9 -6.011 -9.518 7.281 1.00 4.53 ACSY o ATOM 213 HB1 SER 9 -6.479 -8.823 7.977 1.00 4.87 ACSY ATOM 214 HB2 SER 9 -4.947 -9.286 7.238 1.00 4.92 ACSY 25 ATOM 215 OG SER 9 -6.157 -10.817 7.794 1.00 5.09 ACSY ATOM 216 HG SER 9 -6.454 -10.725 8.689 1.00 5.60 ACSY ATOM 217 C SER 9 -6.030 -10.425 4.941 1.00 3.30 ACSY ATOM 218 0 SER 9 -5.335 -11.352 5.339 1.00 3.79 ACSY ATOM 219 N HIS 10 -6.330 -10.180 3.653 1.00 3.01 ACSY ATOM 220 HN HIS 10 -6.900 -9.398 3.403 1.00 3.18 ACSY ATOM 221 CA HIS 10 -5.808 -11.075 2.636 1.00 3.08 ACSY ATOM 222 HA HIS 10 -6.017 -12.098 2.963 1.00 3.58 ACSY ATOM 223 CB HIS 10 -6.488 -10.781 1.301 1.00 3.80 ACSY ATOM 224 HB1 HIS 10 -6.423 -9.719 1.065 1.00 4.15 ACSY ATOM 225 HB2 HIS 10 -5.999 -11.329 0.496 1.00 4.03 ACSY ATOM 226 CG HIS 10 -7.941 -11.190 1.371 1.00 4.47 ACSY ATOM 227 CD2 HIS 10 -8.741 -11.366 2.516 1.00 5.19 ACSY ATOM 228 HD2 HIS 10 -8.433 -11.236 3.542 1.00 5.38 ACSY ATOM 229 ND1 HIS 10 -8.700 -11.451 0.285 1.00 4.99 ACSY 392 ATOM 230 HD1 HIS 10 -8.417 -11.412 -0.653 1.00 5.01 ACSY a.

a a.

a a a.

a a a a a. a 15 20 25 ATOM 231 ATOM 232 ATOM 233 ATOM 234 ATOM 235 ATOM 236 ATOM 237 ATOM 238 ATOM 239 ATOM 240 ATOM 241 ATOM 242 ATOM 243 ATOM 244 ATOM 245 ATOM 246 ATOM 247 ATOM 248 ATOM 249 ATOM 250 ATOM 251 ATOM 252 ATOM 253 ATOM 254 ATOM 255 ATOM 256 ATOM 257 ATOM 258 ATOM 259 ATOM 260 ATOM 261 ATOM 262 ATOM 263 ATOM 264 ATOM 265 ATOM 266 ATOM 267 ATOM 268 CE1 HIS HE1 HIS NE2 HIS C HIS 0 HIS N GLU HN GLU CA GLU HA GLU CB GLU HB1 GLU HB2 GLU CG GLU HG1 GLU HG2 GLU CD GLU OE1 GLU OE2 GLU C GLU O GLU N LYS HN LYS CA LYS HA LYS C3 LYS HB1 LYS HB2 LYS CG LYS HG1 LYS HG2 LYS CD LYS HD1 LYS HD2 LYS CE LYS HE1 LYS HE2 LYS NZ LYS HZ1 LYS -9.921 -11.776 -10.757 -12.039 -9.970 -11.732 -4.297 -10.887 -3.798 -10.190 -3.608 -11.560 -4.074 -12.116 -2.170 -11.475 -1.900 -10.433 -1.652 -12.378 -2.480 -12.680 -1.249 -13.287 -0.588 -11.678 0.236 -11.351 -1.007 -10.797 -0.052 -12.631 -0.462 -12.509 0.770 -13.484 -1.631 -11.926 -0.885 -11.225 -2.068 -13.151 -2.665 -13.656 -1.651 -13.737 -0.660 -14.174 -2.657 -14.809 -3.618 -14.343 -2.325 -15.289 -2.836 -15.863 -1.928 -16.461 -2.979 -15.371 -4.028 -16.776 -4.122 -17.517 -4.947 -16.189 -3.880 -17.482 -3.757 -16.755 -3.003 -18.129 -5.039 -18.306 -4.893 -18.761 0.743 0.111 2.086 2.519 1.644 3.458 4.140 3.463 3.639 4.570 5.208 4.136 5.406 4.775 5.892 6.476 7.629 6.144 2.112 1.439 1.778 2.403 0.511 0.665 0.099 -0.118 -0.822 1.192 1.277 2.154 0.902 1.695 0.909 -0.446 -1.249 -0.447 -0.770 -1.694 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1. 00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 5.85 6.59 5.97 2.47 2.49 2.40 2.73 2.34 2.44 2.96 3.18 3.13 3.54 3.67 3.72 4.24 4.62 4.74 2.16 2.18 2.44 2.76 2 .66 3 .12 3 .44 3 .47 3 .71 4.37 4 .60 4.75 5 .03 5.34 4.95 5 .94 6.28 6 .22 6.49 6.68

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

393

S

*5 S S

S

*5S*

S

S

S S S. S 555555

S

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 HZ2 LYS HZ3 LYS C LYS O LYS N MET HN MET CA MET HA MET CB MET HB1 MET HB2 MET CG MET HG1 MET HG2 MET SD MET CE MET HE1 MET HE2 MET HE3 MET C MET O MET N PRO CD PRO HD1 PRO HD2 PRO CA PRO HA PRO CB PRO HB1 PRO HB2 PRO CG PRO HG1 PRO HG2 PRO C PRO 0 PRO N TRP HN TRP CA TRP 12 -5.161 -19.036 -5.889 -17.708 -1.559 -12.653 -2.557 -12.154 -0.285 -12.340 0.468 -12.807 -0.002 -11.321 0.048 -11.826 -1.083 -10.233 -1.621 -10.253 -0.604 -9.256 -2.079 -10.379 -2.825 -11.136 -2.613 -9.441 -1.252 -10.822 -1.731 -12.557 -0.919 -13.162 -2.610 -12.689 -1.964 -12.914 1.366 -10.713 1.843 -10.785 1.978 -10.111 1.417 -10.040 0.542 -9.391 1.120 -11.027 3.279 -9.483 3.942 -10.074 3.782 -9.370 4.298 -8.423 4.482 -10.175 2.535 -9.470 2.258 -8.490 2.720 -10.108 3.148 -8.078 3.558 -7.757 2.515 -7.281 2.196 -7.649 2.298 -5.880 3.264 -5.479 -0.808 -0.563 -1.057 -0.873 -0.411 -1.882 -2.848

A

-1.879 -0.932 -1.940 -3.044 -2.820 -3.194 -4.580 -4.631 -5.035 -5.261 -3.628 -1.555 -0.430 -2.602 -3.937 -3.941 -4.274 -2.491 -1.865 -3.928 -4.086 -4.155 -4.817 -5.202 -5.663 -1.937 -0.831 -2.805 -3.689 -2.458 1.00 6.61 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 2.13 2.63 1.83 2.22 1.83 2.37 2.34 2.33 2.63 3.26 3 .64 3 .50 4 .25 4 .96 5.13 5 .43 5.19 1.57 1.67 1.40 1.46 1.49 1.69 1.35 1.54 1.38 1.44 1.60 1.40 1.44 1.60 1.26 1.41 1.17 1.17 1.26

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

-0.039 1.00 6.91 ACSY ATOM 307 HA TRP 15 -2.133 1.00 1.41 394 ATOM 308 CB TRP 15 1.788 -5.095 -3.682 1.00 1.44 ACSY ATOM 309 HB1 TRP 15 1.338 -4.163 -3.358 1.00 1.41 ACSY ATOM 310 HB2 TRP 15 2.617 -4.840 -4.338 1.00 1.60 ACSY ATOM 311 CG TRP 15 0.749 -5.891 -4.464 1.00 1.71 ACSY ATOM 312 CD2 TRP 15 0.397 -5.729 -5.840 1.00 2.23 ACSY ATOM 313 CE2 TRP 15 -0.624 -6.690 -6.124 1.00 2.46 ACSY ATOM 314 CE3 TRP 15 0.850 -4.872 -6.832 1.00 2.89 ACSY ATOM 315 HE3 TRP 15 1.621 -4.148 -6.614 1.00 2.88 ACSY ATOM 316 CD1 TRP 15 -0.041 -6.920 -3.958 1.00 2.00 ACSY ATOM 317 HD1 TRP 15 0.019 -7.304 -2.955 1.00 2.35 ACSY ATOM 318 NE1 TRP 15 -0.860 -7.395 -4.942 1.00 2.25 ACSY ATOM 319 HE1 TRP 15 -1.511 -8.119 -4.835 1.00 2.53 ACSY ATOM 320 CZ2 TRP 15 -1.175 -6.776 -7.396 1.00 3.15 ACSY ATOM 321 HZ2 TRP 15 -1.946 -7.503 -7.606 1.00 3.33 ACSY 1 5 ATOM 322 CZ3 TRP 15 0.294 -4.951 -8.134 1.00 3.75 ACSY ATOM 323 HZ3 TRP 15 0.643 -4.288 -8.912 1.00 4.43 ACSY ATOM 324 CH2 TRP 15 -0.720 -5.904 -8.416 1.00 3.82 ACSY ATOM 325 HH2 TRP 15 -1.143 -5.965 -9.408 1.00 4.49 ACSY ATOM 326 C TRP 15 1.304 -5.744 -1.294 1.00 1.18 ACSY 20 ATOM 327 0 TRP 15 0.867 -4.651 -0.965 1.00 1.21 ACSY ATOM 328 N PHE 16 0.973 -6.903 -0.692 1.00 1.17 ACSY ATOM 329 HN PHE 16 1.327 -7.775 -1.019 1.00 1.22 ACSY ATOM 330 CA PHE 16 0.059 -6.845 0.428 1.00 1.18 ACSY ATOM 331 HA PHE 16 0.044 -5.809 0.779 1.00 1.12 ACSY 25 ATOM 332 CB PHE 16 -1.326 -7.277 -0.014 1.00 1.33 ACSY ATOM 333 HB1 PHE 16 -1.600 -6.763 -0.930 1.00 1.39 ACSY ATOM 334 HB2 PHE 16 -1.339 -8.347 -0.224 1.00 1.50 ACSY ATOM 335 CG PHE 16 -2.330 -6.975 1.064 1.00 1.35 ACSY ATOM 336 CD1 PHE 16 -2.511 -7.882 2.139 1.00 1.69 ACSY ATOM 337 HD1 PHE 16 -1.952 -8.802 2.163 1.00 2.35 ACSY ATOM 338 CD2 PHE 16 -3.078 -5.770 1.044 1.00 1.93 ACSY ATOM 339 HD2 PHE 16 -2.949 -5.068 0.233 1.00 2.63 ACSY ATOM 340 CE1 PHE 16 -3.421 -7.589 3.179 1.00 1.71 ACSY ATOM 341 HE1 PHE 16 -3.542 -8.282 4.000 1.00 2.35 ACSY ATOM 342 CE2 PHE 16 -3.989 -5.481 2.087 1.00 1.99 ACSY ATOM 343 HE2 PHE 16 -4.552 -4.562 2.072 1.00 2.73 ACSY ATOM 344 CZ PHE 16 -4.160 -6.390 3.152 1.00 1.47 ACSY ATOM 345 HZ PHE 16 -4.856 -6.167 3.947 1.00 1.53 ACSY ATOM 346 C PHE 16 0.548 -7.740 1.558 1.00 1.37 ACSY 395

ATOM

ATOM

347 348 0* ATOM 349 ATOM 350 ATOM 351 ATOM 352 ATOM 353 ATOM 354 ATOM 355 1 0 ATOM 356 ATOM 357 ATOM 358 ATOM 359 ATOM 360 1 5 ATOM 361 ATOM 362 ATOM 363 ATOM 364 ATOM 365 20 ATOM 366 ATOM 367 ATOM 368 ATOM 369 ATOM 370 ATOM 371 ATOM 372 ATOM 373 ATOM 374 ATOM 375 ATOM 376 ATOM 377 ATOM 378 ATOM 379 ATOM 380 ATOM 381 ATOM 382 ATOM 383 ATOM 384 ATOM 385 O PHE N HIS HN HIS CA HIS HA HIS CB HIS HB1 HIS HB2 HIS CG HIS CD2 HIS HD2 HIS ND1 HIS HD1 HIS CE1 HIS HE1 HIS NE2 HIS C HIS O HIS N GLY HN GLY CA GLY HA1 GLY HA2 GLY C GLY O GLY N LYS HN LYS CA LYS HA LYS CB LYS HB1 LYS HB2 LYS CG LYS HG1 LYS HG2 LYS CD LYS HD1 LYS HD2 LYS CE LYS 0.132 1.463 1.791 -6.227 1.977 -7.883 1.547 -8.888 3.491 -7.940 3.901 -7.013 3.887 -8.073 3.919 -9.100 3.426 -9.460 2.655 -8.949 4.869 -9.993 5.391 -10.000 4.957 -10.872 5.634 -11.713 4.096 -10.571 1.514 -7.196 1.908 -6.081 0.651 -7.943 0.407 -8.855 0.114 -7.413 -0.900 -7.799 0.077 -6.328 0.987 -7.817 0.506 -8.052 2.297 -7.881 2.613 -7.677 3.239 -8.257 2.679 -8.337 3.882 -9.592 3.105 -10.332 4.443 -9.483 4.813 -10.095 5.543 -9.323 4.238 -10.281 5.538 -11.373 4.808 -12.149 6.099 -11.190 6.487 -11.868 -8.881 -7.147 1.707 2.337 2.135 3.467 3.425 3.414 3.013 A Al A 2.548 1.282 0.723 2.899 3.728 1.886 1.868 0.897 4.746 5.067 5.443 5.127 6.682 6.792 6.587 7.877 8.979 7.575 6.648 8.614 9.549 8.246 8.058 7.318 9.350 9.593 10.257 8.929 8.700 8.012 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.98 1.18 1.30 1.33 1.64 1.75 1.78 2.06 2.50 3.04 2.88 3.11 3.08 3.95 4.63 3.96 1.30 1.46 1.54 1.71 1.88 2.11 1.95 2.10 2.46 1.96 1.76 2.25 2.47 2.42 2.52 2.47 2.83 3.35 3.28 2.77 2.91 3 .00

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY 10.020 1.00 3.23 396 ATOM 386 HE1 LYS 19 7.245 -11.116 10.239 1.00 3.73 ACSY ATOM 387 HE2 LYS 19 5.940 -12.067 10.942 1.00 3.52 ACSY ATOM 388 NZ LYS 19 7.176 -13.095 9.640 1.00 3.46 ACSY ATOM 389 HZ1 LYS 19 7.720 -12.932 8.769 1.00 3.67 ACSY ATOM 390 HZ2 LYS 19 6.478 -13.849 9.476 1.00 3.66 ACSY ATOM 391 HZ3 LYS 19 7.822 -13.381 10.403 1.00 3.79 ACSY ATOM 392 C LYS 19 4.306 -7.172 8.755 1.00 2.17 ACSY ATOM 393 0 LYS 19 4.560 -6.650 9.834 1.00 2.83 ACSY ATOM 394 N ILE 20 4.908 -6.874 7.589 1.00 1.56 ACSY ATOM 395 HN ILE 20 4.644 -7.343 6.747 1.00 1.50 ACSY ATOM 396 CA ILE 20 5.949 -5.857 7.578 1.00 1.44 ACSY ATOM 397 HA ILE 20 6.849 -6.312 7.999 1.00 1.51 ACSY ATOM 398 CB ILE 20 6.204 -5.391 6.146 1.00 1.24 ACSY ATOM 399 HB ILE 20 6.595 -4.374 6.180 1.00 1.31 ACSY 5 ATOM 400 CG2 ILE 20 7.246 -6.285 5.477 1.00 1.23 ACSY ATOM 401 HG21 ILE 20 8.154 -6.339 6.079 1.00 1.53 ACSY ATOM 402 HG22 ILE 20 6.865 -7.299 5.352 1.00 1.60 ACSY ATOM 403 HG23 ILE 20 7.516 -5.901 4.495 1.00 1.66 ACSY ATOM 404 CG1 ILE 20 4.901 -5.391 5.341 1.00 1.26 ACSY 20 ATOM 405 HG11 ILE 20 4.514 -6.407 5.274 1.00 1.41 ACSY ATOM 406 HG12 ILE 20 4.148 -4.803 5.865 1.00 1.71 ACSY SATOM 407 CD1 ILE 20 5.106 -4.826 3.935 1.00 1.07 ACSY SATOM 408 HD11 ILE 20 5.308 -3.756 3.974 1.00 1.34 ACSY ATOM 409 HD12 ILE 20 5.947 -5.310 3.439 1.00 1.53 ACSY 25 ATOM 410 HD13 ILE 20 4.219 -4.979 3.321 1.00 1.29 ACSY ATOM 411 C ILE 20 5.535 -4.680 8.456 1.00 1.49 ACSY ATOM 412 0 ILE 20 4.379 -4.521 8.830 1.00 1.58 ACSY ATOM 413 N SER 21 6.567 -3.873 8.754 1.00 1.47 ACSY ATOM 414 HN SER 21 7.483 -4.069 8.405 1.00 1.41 ACSY ATOM 415 CA SER 21 6.325 -2.711 9.590 1.00 1.57 ACSY ATOM 416 HA SER 21 5.490 -2.945 10.233 1.00 1.67 ACSY ATOM 417 CB SER 21 7.572 -2.415 10.418 1.00 1.63 ACSY ATOM 418 HB1 SER 21 7.829 -3.265 11.051 1.00 1.95 ACSY ATOM 419 HB2 SER 21 8.425 -2.205 9.774 1.00 1.66 ACSY ATOM 420 OG SER 21 7.364 -1.299 11.246 1.00 2.23 ACSY ATOM 421 HG SER 21 8.215 -0.910 11.397 1.00 2.35 ACSY ATOM 422 C SER 21 5.969 -1.511 8.719 1.00 1.51 ACSY ATOM 423 0 SER 21 4.830 -1.066 8.637 1.00 1.58 ACSY ATOM 424 N ARG 22 7.041 -1.037 8.086 1.00 1.44 ACSY 397

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

*A

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

S..o ATOM

ATOM

ATOM

30 25 ATOM

ATOM

ATOM

ATOM

ATOM

3 0 ATOM

ATOM

ATOM

ATOM

ATOM

3 5 ATOM

ATOM

ATOM

ATOM

ATOM

425 HN ARG 426 CA ARG 427 HA ARG 428 CB ARG 429 HB1 ARG 430 HB2 ARG 431 CG ARG 432 HG1 ARG 433 HG2 ARG 434 CD ARG 435 HD1 ARG 436 HD2 ARG 437 NE ARG 438 HE ARG 439 CZ ARG 440 NH1 ARG 441 HH11 ARG 442 HH12 ARG 443 NH2 ARG 444 HH21 ARG 445 HH22 ARG 446 C ARG 447 0 ARG 448 N GLU 449 HN GLU 450 CA GLU 451 HA GLU 452 CB GLU 453 HB1 GLU 454 HB2 GLU 455 CG GLU 456 HG1 GLU 457 HG2 GLU 458 CD GLU 459 OE1 GLU 460 OE2 GLU 461 C GLU 462 O GLU 463 N GLU 7.928 -1.480 8.213 1.00 1.46 6.929 0.118 7.212 1.00 1.40 6.228 -0.136 6.413 1.00 1.34 6.454 1.329 8.012 1.00 1.57 5.552 1.070 8.568 1.00 1.98 7.211 1.597 8.747 1.00 1.53 6.172 2.525 7.105 1.00 1.89 6.960 2.609 6.357 1.00 2.11 5.241 2.360 6.562 1.00 2.13 6.079 3.830 7.898 1.00 2.36 5.505 3.705 8.815 1.00 2.77 5.619 4.623 7.309 1.00 2.76 7.408 4.298 8.262 1.00 2.61 7.953 4.826 7.612 1.00 2.68 7.899 4.012 9.487 1.00 3.36 9.114 4.436 9.823 1.00 3.96 9.658 4.964 9.171 1.00 3.94 9.484 4.227 10.729 1.00 4.64 7.180 3.311 10.359 1.00 3.92 6.266 2.990 10.110 1.00 3.79 7.553 3.104 11.264 1.00 4.68 8.316 0.372 6.623 1.00 1.31 8.490 0.687 5.452 1.00 1.22 9.283 0.196 7.543 1.00 1.36 9.048 -0.060 8.479 1.00 1.46 10.663 0.345 7.179 1.00 1.31 10.745 1.195 6.502 1.00 1.29 11.448 0.560 8.468 1.00 1.43 12.274 1.226 8.280 1.00 1.45 10.800 1.042 9.187 1.00 1.54 11.969 -0.737 9.080 1.00 1.43 11.142 -1.361 9.421 1.00 1.45 12.530 -1.304 8.349 1.00 1.33 12.877 -0.422 10.271 1.00 1.56 14.004 -0.913 10.294 1.00 1.99 12.446 0.310 11.160 1.00 1.89 11.103 -0.934 6.485 1.00 1.18 11.758 -0.940 5.451 1.00 1.08 10.675 -2.009 7.156 1.00 1.21

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

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ACSY

ACSY

ACSY

ACSY

ACSY

398 ATOM 464 HN GLU 24 10.161 -1.880 8.019 1.00 1.31 S

S

S.

S S

*SS*

*5 S S *5

S

S

*5S*

S

*5

S

S

S

ATOM 465 ATOM 466 ATOM 467 ATOM 468 ATOM 469 ATOM 470 ATOM 471 ATOM 472 1 0 ATOM 473 ATOM 474 ATOM 475 ATOM 476 ATOM 477 1 5 ATOM 478 ATOM 479 ATOM 480 ATOM 481 ATOM 482 20 ATOM 483 ATOM 484 ATOM 485 ATOM 486 ATOM 487 25 ATOM 488 ATOM 489 ATOM 490 ATOM 491 ATOM 492 ATOM 493 ATOM 494 ATOM 495 ATOM 496 ATOM 497 ATOM 498 ATOM 499 ATOM 500 ATOM 501 ATOM 502 CA GLU HA GLU CB GLU HB1 GLU HB2 GLU CG GLU HG1 GLU HG2 GLU CD GLU OE1 GLU OE2 GLU C GLU O GLU N SER HN SER CA SER HA SER CB SER HBI SER HB2 SER OG SER HG SER C SER O SER N GLU HN GLU CA GLU HA GLU CB GLU HB1 GLU HB2 GLU CG GLU HG1 GLU HG2 GLU CD GLU OE1 GLU OE2 GLU C GLU 10.984 12.057 10.176 9.127 10.513 10.308 10.108 9.595 11.725 11.986 12.549 10.657 11.391 9.516 8.975 9.086 9.332 7.581 7.144 7.098 7.292 6.367 9.826 9.979 10.269 10.126 10.973 10.449 10.916 10.192 10.555 12.275 13.013 12.602 12.200 13.249 11.092 12.418 -3.332 -3.491 -4.351 -4.292 -5.354 -4.113 -3.069 -4.725 -4.465 -4.399 -4.800 -3.423 -4.009 -2.794 -2.319 -2.818 -3.806 -2.585 -3.083 -2.976 -1.213 -1.143 -1.755 -1.879 -0.710 -0.668 0.359 0.553 1.574 2.279 1.265 2.244 1.509 2.689 3.331 3.748 3.745 -0.061 6.657 6.800 7.450 7.161 7.207 8.954 9.197 9.506 9.413 10.613 8.564 5.163 4.378 4.828 5.521 3.435 3.039 3.382 2.519 4.277 3.290 3.093 2.607 1.398 3.331 4.312 2.667 1.728 3.588 3.205 4.566 3.747 4.042 2.808 4.823 5.310 5.163 2.350 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.15 1.16 1.26 1.25 1.24 1.44 1.79 1.59 1.80 2.37 2.30 0.99 0.94 0.96 1.04 0.84 0.83 0.86 1.16 1.37 1.53 1.79 0.75 0.67 0.83 0.92 0.81 0.73 0.92 0.91 0.99 0.99 1.02 0.96 1.11 1.46 1.59 0.81

ACSY

ACSY

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399

ATOM

ATOM

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ATOM

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@0 o ATOM *.o.oo ATOM

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1: 5: ATOM

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oATOM oo 20 ATOM

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25 ATOM

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3 5 ATOM

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ATOM

ATOM

ATOM

C. 0*ATOM C ATOM

ATOM

ATOM

503 0 GLU 504 N GLN 505 HN GLN 506 CA GLN 507 HA GLN 508 CB GLN 509 HB1 GLN 510 HB2 GLN 511 CG GLN 512 HG1 GLN 513 HG2 GLN 514 CD GLN 515 OE1 GLN 516 NE2 GLN 517 HE21 GLN 518 HE22 GLN 519 C GLN 520 0 GLN 521 N ILE 522 HN ILE 523 CA ILE 524 HA ILE 525 CB ILE 526 HB ILE 527 CG2 ILE 528 HG21 ILE 529 HG22 ILE 530 HG23 ILE 531 CG1 ILE 532 HG11 ILE 533 HG12 ILE 534 CD1 ILE 535 HD11 ILE 536 HD12 ILE 537 HD13 ILE 538 C ILE 539 0 ILE 540 N VAL 541 HN VAL 13.065 0.487 1.465 1.00 0.80 12.875 -1.065 3.123 1.00 0.86 12.277 -1.507 3.790 1.00 0.90 14.219 -1.566 2.882 1.00 0.87 14.835 -0.723 2.559 1.00 0.91 14.790 -2.213 4.143 1.00 0.96 15.731 -2.709 3.904 1.00 0.98 15.021 -1.440 4.876 1.00 1.16 13.821 -3.221 4.753 1.00 1.16 12.932 -2.717 5.129 1.00 1.40 13.503 -3.949 4.006 1.00 1.25 14.498 -3.959 5.910 1.00 1.50 14.807 -5.142 5.831 1.00 1.87 14.704 -3.176 6.983 1.00 2.20 14.425 -2.215 6.976 1.00 2.69 15.141 -3.541 7.806 1.00 2.54 14.113 -2.574 1.741 1.00 0.78 15.035 -2.796 0.970 1.00 0.79 12.907 -3.163 1.690 1.00 0.73 12.196 -2.957 2.367 1.00 0.75 12.636 -4.086 0.648 1.00 0.69 13.465 -4.779 0.605 1.00 0.73 11.323 -4.742 0.999 1.00 0.72 10.679 -3.974 1.446 1.00 0.74 10.654 -5.289 -0.242 1.00 0.76 9.998 -4.544 -0.686 1.00 1.25 11.397 -5.577 -0.983 1.00 1.29 10.060 -6.167 0.002 1.00 1.25 11.527 -5.847 2.019 1.00 0.80 11.891 -6.741 1.517 1.00 0.84 12.292 -5.547 2.732 1.00 0.83 10.227 -6.157 2.754 1.00 0.89 9.367 -6.002 2.101 1.00 1.37 10.211 -7.189 3.096 1.00 1.38 10.107 -5.513 3.623 1.00 1.36 12.543 -3.320 -0.664 1.00 0.63 12.982 -3.763 -1.718 1.00 0.66 11.918 -2.146 -0.520 1.00 0.58 11.536 -1.878 0.370 1.00 0.60

ACSY

ACSY

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ACSY

ACSY

ACSY

ACSY

ACSY

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ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

400 ATOM 542 CA VAL 29 11.809 -1.280 -1.670 1.00 0.57 ATOM 543 ATOM 544 ATOM 545 ATOM 546 ATOM 547 ATOM 548 ATOM 549 ATOM 550 ATOM 551 ATOM 552 ATOM 553 ATOM 554 ATOM 555 ATOM 556 ATOM 557 ATOM 558 ATOM 559 ATOM 560 ATOM 561 ATOM 562 ATOM 563 ATOM 564 ATOM 565 ATOM 566 ATOM 567 ATOM 568 ATOM 569 ATOM 570 ATOM 571 ATOM 572 ATOM 573 ATOM 574 ATOM 575 ATOM 576 ATOM 577 ATOM 578 ATOM 579 ATOM 580

HA

CB

HB

CG1 HG11 HG12 HG13 CG2 HG21 HG22 HG23

C

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

O VAL N LEU HN LEU CA LEU HA LEU CB LEU HB1 LEU HB2 LEU CG LEU HG LEU CD1 LEU HD11 LEU HD12 LEU HD13 LEU CD2 LEU HD21 LEU HD22 LEU HD23 LEU C LEU 0 LEU N ILE HN ILE CA ILE HA ILE CB ILE HB ILE 11.361 10.981 11.060 11.526 12.578 11.435 10.983 9.507 9.396 9.035 8.962 13.206 13.469 14.075 13.817 15.421 15.423 16.145 16.657 15.407 17.108 16.646 18.413 19.102 18.240 18.894 17.369 17.485 18.273 16.538 15.967 16.749 15.479 14.863 15.885 16.980 15.294 14.366 -1.861 -0.052 0.060 1.224 1.367 1.184 2.094 -0.234 -0.564 -0.972 0.704 -0.864 -0.587 -0.834 -1.124 -0.478 0.538 -0.569 0.357 -0.688 -1.741 -2.586 -1.409 -2.251 -1.168 -0.551 -2.128 -3.209 -1.656 -1.826 -1.468 -1.139 -2.709 -2.897 -3.766 -3.793 -5.098 -5.267 -2.473 -1.273 -0.190 -1.915 -1.670 -3.001 -1.559 -1.635 -2.668 -0.988 -1.523 -2.106 -3.269 -1.093 -0.169 -1.362 -1.771 -0.025 0.175 0.757 0.048 -0.437 -0.653 -0.606 -1.699 -0.182 1.488 1.573 1.856 2.122 -2.387 -3.271 -2.188 -1.411 -3.057 -3.064 -2.599 -3.138 1.00 1.00 1.00 1.00 1.00 1.00 1 nn 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 iO00 0.58 0.55 0.57 0.66 1.22 1.36 1. 09 0.54 1.13 1.22 0.99 0.67 0.73 0.72 0.70 0.84 0.88 0.90 1.00 0.86 0.94 0 .87 1.06 1.65 1.39 1 .42 1.00 1.36 1 .42 1 .42 0.86 0.96 0.79 0.74 0.85 0.91 0.83 0.82

ACSY

ACSY

ACSY

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ACSY

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ACSY

ACSY

401 ATOM 581 CG2 ILE ATOM 582 HG21 ILE ATOM 583 HG22 ILE ATOM 584 HG23 ILE ATOM 585 CG1 ILE ATOM 586 HG11 ILE ATOM 587 HG12 ILE ATOM 588 CD1 ILE ATOM 589 HD11 ILE ATOM 590 HD12 ILE ATOM 591 HD13 ILE ATOM 592 C ILE ATOM 593 O ILE ATOM 594 N GLY 15 ATOM 595 HN GLY ATOM 596 CA GLY ATOM 597 HA1 GLY ATOM 598 HA2 GLY .ATOM 599 C GLY 20 ATOM 600 0 GLY ATOM 601 N SER ATOM 602 HN SER ATOM 603 CA SER ATOM 604 HA SER 25 ATOM 605 CB SER ATOM 606 HB1 SER ATOM 607 HB2 SER ATOM 608 OG SER ATOM 609 HG SER ATOM 610 C SER ATOM 611 O SER ATOM 612 N LYS ATOM 613 HN LYS ATOM 614 CA LYS ATOM 615 HA LYS ATOM 616 CB LYS ATOM 617 HB1 LYS ATOM 618 HB2 LYS ATOM 619 CG LYS 16.223 -6.208 -2.978 1.00 0.92 16.406 -6.191 -4.052 1.00 1.28 17.173 -6.098 -2.465 1.00 1.41 15.792 -7.168 -2.718 1.00' 1.39 14.972 -5.149 -1.116 1.00 0.78 14.811 -4.156 -0.725 1.00 0.75 14.028 -5.671 -1.003 1.00 0.77 16.065 -5.856 -0.312 1.00 0.85 16.217 -6.873 -0.675 1.00 1.28 17.013 -5.324 -0.393 1.00 1.27 15.797 -5.912 0.743 1.00 1.42 15.353 -3.501 -4.439 1.00 0.88 16.071 -3.241 -5.396 1.00 0.98 14.020 -3.598 -4.448 1.00 0.83 13.520 -3.793 -3.580 1.00 0.77 13.328 -3.443 -5.701 1.00 0.89 12.611 -4.259 -5.764 1.00 0.91 14.070 -3.566 -6.486 1.00 0.97 12.628 -2.089 -5.833 1.00 0.92 12.104 -1.537 -4.876 1.00 1.40 12.672 -1.624 -7.104 1.00 0.97 13.132 -2.162 -7.810 1.00 1.35 12.054 -0.346 -7.460 1.00 0.96 11.133 -0.582 -7.989 1.00 0.99 11.750 0.491 -6.214 1.00 0.90 10.952 0.035 -5.627 1.00 1.26 12.629 0.580 -5.578 1.00 1.21 11.329 1.783 -6.570 1.00 1.66 11.623 2.365 -5.881 1.00 1.90 12.984 0.384 -8.436 1.00 1.11 13.387 -0.169 -9.452 1.00 1.60 13.294 1.649 -8.076 1.00 1.03 12.926. 2.046 -7.236 1.00 1.20 14.178 2.419 -8.940 1.00 1.14 14.631 3.213 -8.341 1.00 1.17 15.231 1.487 -9.523 1.00 1.27 15.416 0.670 -8.836 1.00 1.39 14.848 1.039 -10.443 1.00 1.59 16.526 2.227 -9.830 1.00 1.56

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

402 ATOM 620 HG1 LYS 34 16.882 1.932 -10.816 1.00 1.98 ACSY 15 20 ATOM 621 ATOM 622 ATOM 623 ATOM 624 ATOM 625 ATOM 626 ATOM 627 ATOM 628 ATOM 629 ATOM 630 ATOM 631 ATOM 632 ATOM 633 ATOM 634 ATOM 635 ATOM 636 ATOM 637 ATOM 638 ATOM 639 ATOM 640 ATOM 641 ATOM 642 ATOM 643 ATOM 644 ATOM 645 ATOM 646 ATOM 647 ATOM 648 ATOM 649 ATOM 650 ATOM 651 ATOM 652 ATOM 653 ATOM 654 ATOM 655 ATOM 656 ATOM 657 HG2 LYS CD LYS HD1 LYS HD2 LYS CE LYS HE1 LYS HE2 LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS 0 LYS N THR HN THR CA THR HA THR CB THR HB THR 16.327 3.297 17.604 1.940 18.466 2.583 17.229 2.189 18.042 0.476 17.222 -0.176 18.340 0.189 19.169 0.213 18.904 0.450 19.427 -0.793 19.980 0.796 13.392 3.022 13.360 4.225 12.770 2.071 12.840 1.119 11.996 2.414 12.674 2.903 11.463 1.118 10.411 1.028 12.112 0.017 11.493 -0.372 11.664 1.065 12.725 1.122 11.270 0.138 11.159 1.897 10.838 3.371 10.049 3.716 10.791 3.768 11.467 3.432 9.743 4.682 9.774 4.746 9.982 6.051 10.927 6.472 10.037 5.961 8.849 7.021 8.578 7.982 8.214 6.704 8.489 5.903 -9.873 -8.785 -8.965 -7.793 -8.819 -8.516 -9.827 -7.932 -6.955 -7.988 -8.223 -10.090 -10.315 -10.791 -10.507 -11.968 -12.659 -12.553 -12.316 -11.959 -11.356 -14.055 -14.301 -14.465 -14.541 -11.673 -12.545 -10.408 -9.765 -10.001 -8.912 -10.639 -10.296 -11.724 -10.280 -10.989 -9.135 -8.604 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 2.07 1.57 2.08 1.79 1.98 2.46 2.35 2.48 2.82 2.83 2.84 1.20 1.30 1.22 1.19 1.35 1.51 1.47 1.54 1.54 1.78 1.88 2.17 2.18 2.38 1.26 1.40 1.13 1.11 1.11 1.03 1.32 1.36 1.46 1.40 1.87 1.73 2.24

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

OG1 HG1 CG2 HG21 HG22 HG23

C

0

N

HN

CA

HA

CB

HB1 HB2

CG

ODI

ND2

THR

THR

THR

THR

THR

THR

THR

THR

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ASN

ATOM 658 HD21 ASN 403 ATOM 659 HD22 ASN 36 7.458 7.265 -8.799 1.00 1.89 ACSY ATOM 660 ATOM 661 ATOM 662 ATOM 663 ATOM 664 ATOM 665 ATOM 666 ATOM 667 1 0 ATOM 668 ATOM 669 ATOM 670 ATOM 671 ATOM 672 1 5 ATOM 673 ATOM 674 ATOM 675 ATOM 676 ATOM 677 20 ATOM 678 ATOM 679 ATOM 680 ATOM 681 ATOM 682 ATOM 683 ATOM 684 ATOM 685 ATOM 686 ATOM 687 ATOM 688 ATOM 689 ATOM 690 ATOM 691 ATOM 692 ATOM 693 ATOM 694 ATOM 695 ATOM 696 C ASN O ASN N GLY HN GLY CA GLY HA1 GLY HA2 GLY C GLY O GLY N LYS HN LYS CA LYS HA LYS CB LYS HB1 LYS HB2 LYS CG LYS HG1 LYS HG2 LYS CD LYS HD1 LYS HD2 LYS CE LYS HE1 LYS HE2 LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS 0 LYS N PHE HN PHE CA PHE HA PHE CB PHE HB1 PHE 1 1 1 1 1 8.395 7.967 7.767 8.185 6.471 6.414 5.713 3.645 6.256 1.646 5.163 1.097 7.357 1.229 8.230 1.727 7.224 0.062 6.650 -0.681 8.600 -0.465 9.286 -0.306 8.978 0.107 8.571 -1.950 9.029 -2.087 7.540 -2.286 9.309 -2.806 8.686 -2.936 0.210 -2.291 9.685 -4.175 0.256 -4.063 8.792 -4.752 0.491 -4.959 9.949 -5.130 1.362 -4.439 0.737 -5.869 6.450 0.467 6.551 1.586 5.675 -0.506 5.671 -1.410 4.872 -0.202 5.507 0.383 3.655 0.623 3.227 1.128 3.952 1.391 -9.425 -8.779 -8.720 -8.112 -8.173 -7.272 -7.836 -6.891 -7.717 -6.049 -6.521 -5.542 -6.434 -7.551 -8.433 -7.877 -6.983 -6.061 -6.751 -7.911 -8.782 -8.141 -7.471 -6.036 -5.548 -5.563 -6.000 -4.389 -3.710 -4.820 -3.956 -5.533 4.111 -10.421 4.217 -11.564 3.500 -9.408 3.468 -8.500 2.894 -9.647 2.630 -10.702 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.10 1.56 0.86 1.02 0.82 0.97 0.91 0.74 0.76 0.69 0.73 0.63 0.66 0.64 0.72 0.62 0.65 0.85 0.96 1. 12 1.85 1.68 1.08 1.37 1.51 1.82 2.15 2.24 2.41 0.53 0.51 0.49 0.53 0.42 0.38 0.44 0.64 0.54

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ATOM 697 HB2 PHE 39 404

S.

S

S

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

698 699 700 701 702 703 704 705 706 707 708 709 710 711 712 713 714 715 716 717 718 719 720 CG PHE CD1 PHE HD1 PHE CD2 PHE HD2 PHE CE1 PHE HE1 PHE CE2 PHE HE2 PHE CZ PHE HZ PHE C PHE 0 PHE N LEU HN LEU CA LEU HA LEU CB LEU HB1 LEU HB2 LEU CG LEU HG LEU CD1 LEU 2.587 1.456 1.369 2.698 3.559 0.444 -0.418 1.685 1.773 0.558 -0.217 4.407 4.351 4.039 4.138 3 .524 2.895 4.673 4.298 5.372 5.388 5.379 4.660 5.225 4.523 3.678 6.839 7.312 7.415 6.896 2.671 3.115 1.422 1.124 0.516 0.826 -0.911 -0.977 -1.278 -0.237 -0.603 -0.265 -0.689 -0.414 -1.410 -1.677 -1.499 -1.842 -1.858 -2.477 -1.469 -2.552 -1.224 -0.306 -2.311 -2.930 -3.120 -4.060 -3.376 -2.340 -1.282 -2.505 -3.148 -1.541 -2.954 -2.800 -2.860 -2.105 -3.784 -1.720 -0.883 -2.208 -2.889 -1.724 -0.707 -1.738 -1.034 -3.128 -5.437 -4.673 -3.652 -6.774 -7.365 -5.233 -4.643 -7.337 -8.357 -6.566 -6.996 -3.673 -4.232 -2.406 -2.021 -1.595 -2.240 -1.014 -0.618 -1.801 0.087 -0.181 1.422 2.094 1.912 1.278 0.211 -0.767 0.821 0.674 -0.476 0.300 -0.448 -1.117 0.576 0.829 0.042 -0.788 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0.48 0.50 0.48 0.55 0.57 0.57 0.61 0.61 0.67 0.62 0.69 0.42 0.52 0.42 0.45 0.49 0.56 0.52 0.67 0.70 0.48 0.45 0.58 1.04 1.23 1.20 0.52 1.19 1.08 1.14 0.52 0.53 0.64 0.74 0.70 0.67 0.80 0.83

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

721 HD11 LEU 722 HD12 LEU 723 HD13 LEU 724 CD2 LEU 725 HD21 LEU 726 HD22 LEU 727 HD23 LEU 728 C LEU 729 0 LEU 730 N ILE 731 HN ILE 732 CA ILE 733 HA ILE 734 CB ILE 735 HB ILE 736 CG2 ILE -0.472 1.00 0.90 405 ATOM 737 HG21 ILE -0.995 -3.896 0.249 1.00 1.49 ACSY ATOM 738 ATOM 739 ATOM 740 ATOM 741 ATOM 742 ATOM 743 ATOM 744 ATOM 745 ATOM 746 ATOM 747 ATOM 748 ATOM 749 ATOM 750 15 ATOM 751 ATOM 752 ATOM 753 ATOM 754 ATOM 755 20 ATOM 756 ATOM 757 ATOM 758 ATOM 759 ATOM 760 ATOM 761 ATOM 762 ATOM 763 ATOM 764 ATOM 765 ATOM 766 ATOM 767 ATOM 768 ATOM 769 ATOM 770 ATOM 771 ATOM 772 ATOM 773 ATOM 774 ATOM 775 HG22 ILE HG23 ILE CG1 ILE HG11 ILE HG12 ILE CD1 ILE HD11 ILE HD12 ILE HD13 ILE C ILE 0 ILE N ARG HN ARG CA ARG HA ARG CB ARG HB1 ARG HB2 ARG CG ARG HG1 ARG HG2 ARG CD ARG HD1 ARG HD2 ARG -2.350 -0.768 -1.891 -2.902 -1.866 -1.568 -0.538 -1.699 -2.220 0.639 0.994 0.322 0.033 0.399 0.520 1.587 2.518 1.585 1.545 0.576 1.639 2.656 2.625 3.642 2.509 3 .147 1.494 1.330 1.960 0.575 0 .655 0.779 -0.099 -0.901 -1.425 -1.381 -0.899 -2.614 -3.208 -3.341 -1.304 -1.319 -2.020 0.096 0.152 0.842 0.361 -2.607 -3.777 -1.960 -1.004 -2.679 -3.740 -2.161 -2.477 -1.071 -2.666 -2.430 -3.752 -2.045 -0.955 -2.375 -2.442 -3.091 -1.924 -2.277 -2.927 -1.892 -1.058 -0.791 -0.674 -2.482 -1.380 -3.624 -4.490 -3.571 -0.646 -1.410 1.131 0.733 1.954 1.653 2.002 0.870 2.484 1.817 1.748 2.951 2.926 4.210 3.974 5.019 4.547 5 .013 6.462 6.902 6.473 7.308 7.276 6.986 8.697 9.113 9.413 10.684 11.108 11.216 8.850 7.894 9.382 4.987 5.100 5.509 5.373 6.274 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.13 1.37 0.86 1.11 1.31 1.08 1.64 1.56 1.42 0.78 0.85 0.80 0.76 0.91 0.94 1.00 1.43 1.42 1.50 2.14 2.02 1.83 2.28 2.31 2.09 2.61 2.42 3.12 3.45 3.59 2.75 2.71 3.42 0.99 0.97 1.16 1.23 1.30

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

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ACSY

ACSY

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ACSY

ACSY

ACSY

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ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

NE

HE

CZ

NH1 HH11 HH12 NH2 HH21 HH22

C

0

N

HN

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ARG

ALA

ALA

CA ALA 406 ATOM 776 HA ALA 43 -2.573 -2.672 6.895 1.00 1.24

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

777 778 779 780 781 782 783 784 785 786 787 788 789 790 791 792 793 794 795 796 797 798 799 CB ALA HB1 ALA HB2 ALA HB3 ALA C ALA O ALA N ARG HN ARG CA ARG HA ARG CB ARG HB1 ARG HB2 ARG CG ARG HG1 ARG HG2 ARG CD ARG HD1 ARG HD2 ARG NE ARG HE ARG CZ ARG NH1 ARG -3.804 -3.818 -4.744 -3.758 -2.708 -2.897 -2.562 -2.409 -2.633 -2.194 -1.859 -2.249 -2.013 -0.363 0.004 -0.192 0.421 0.214 1.495 0.050 -0.714 0.752 0.430 -0.333 0.951 1.767 2.008 2.287 -4.097 -5.004 -4.259 -3.469 -5.603 -6.245 -6.073 -6.013 -5.448 -7.521 -3.518 -4.391 -3.493 -2.628 -4.799 -5.922 -4.502 -3.559 -5.581 -6.468 -5.188 -4.248 -5.939 -5.046 -5.946 -4.217 -4.815 -3.832 -4.908 -5.805 -6.430 -5.865 -6.761 -7.389 -6.807 -5.029 -4.354 -5.075 -5.864 -5.588 -6.430 -6.628 -6.750 -5.905 -8.029 -7.927 -8.873 -8.326 5.318 4.666 5.869 4.689 7.179 6.729 8.483 8.777 9.453 8.987 10.710 11.101 11.484 10.433 9.939 9.746 11.724 12.150 11.568 12.719 12.557 13.866 14.795 14.640 15.647 14.072 13.375 14.925 9.791 9.015 11.001 11.581 11.446 11.181 10.760 9.677 11.050 11.151 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.53 2.07 1.83 1.84 1.63 2.22 1.75 1.96 2.10 2.37 2.62 2.91 3.07 3.13 3.33 3.36 3.97 4.35 4.27 4.54 4.82 5.05 5.75 5.94 6.24 5.19 4.89 5.82 2.44 2.92 2.85 2.99 3.58 3.95 4.38 4.56 4.52 5.32

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

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ACSY

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ACSY

ACSY

800 HH11 ARG 801 HH12 ARG 802 NH2 ARG 803 HH21 ARG 804 HH22 ARG 805 C ARG 806 O ARG 807 N ASP 808 HN ASP 809 CA ASP 810 HA ASP 811 CB ASP 812 HB1 ASP 813 HB2 ASP 814 CG ASP 407 15 20 ATOM 815 OD1 ASP 45 -8.418 -7.677 ATOM 816 OD2 ASP 45 -7.735 -9.206 ATOM 817 C ASP 45 -5.605 -6.925 ATOM 818 0 ASP 45 -5.493 -8.026 ATOM 819 N ASN 46 -5.740 -5.763 ATOM 820 HN ASN 46 -5.829 -4.899 ATOM 821 CA ASN 46 -5.756 -5.792 ATOM 822 HA ASN 46 -6.532 -6.500 ATOM 823 CB ASN 46 -4.387 -6.233 ATOM 824 HB1 ASN 46 -4.122 -7.211 ATOM 825 HB2 ASN 46 -3.615 -5.528 ATOM 826 CG ASN 46 -4.406 -6.314 ATOM 827 OD1 ASN 46 -4.394 -7.387 ATOM 828 ND2 ASN 46 -4.436 -5.106 ATOM 829 HD21 ASN 46 -4.444 -4.271 ATOM 830 HD22 ASN 46 -4.451 -5.024 ATOM 831 C ASN 46 -6.109 -4.403 ATOM 832 0 ASN 46 -7.032 -4.227 ATOM 833 N ASN 47 -5.309 -3.436 ATOM 834 HN ASN 47 -4.574 -3.656 ATOM 835 CA ASN 47 -5.536 -2.065 ATOM 836 HA ASN 47 -6.526 -1.772 ATOM 837 CB ASN 47 -5.464 -1.986 ATOM 838 HB1 ASN 47 -6.266 -2.567 ATOM 839 HB2 ASN 47 -4.517 -2.387 ATOM 840 CG ASN 47 -5.591 -0.529 ATOM 841 OD1 ASN 47 -4.710 0.294 ATOM 842 ND2 ASN 47 -6.746 -0.275 ATOM 843 HD21 ASN 47 -7.421 -0.999 ATOM 844 HD22 ASN 47 -6.949 0.643 ATOM 845 C ASN 47 -4.484 -1.156 ATOM 846 0 ASN 47 -3.291 -1.435 ATOM 847 N GLY 48 -5.012 -0.052 ATOM 848 HN GLY 48 -5.998 0.109 ATOM 849 CA GLY 48 -4.120 0.898 ATOM 850 HA1 GLY 48 -3.167 0.397 ATOM 851 HA2 GLY 48 -3.974 1.729 ATOM 852 C GLY 48 -4.706 1.396 ATOM 853 0 GLY 48 -5.874 1.751 10.617 11.984 12.963 13.488 13.627 13.131 15.078 15.382 15.592 15.189 15.284 17.119 17.711 17.708 17.159 18.704 15.611 16.395 15.126 14.484 15.553 15.194 17.076 17.530 17.437 17.525 17.309 18.164 18.305 18.507 14.919 14.936 14.360 14.383 13.722 13.555 14.413 12.399 12.303 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 5.79 5.88 3.64 3.97 3.82 4.02 4.17 4.53 4.87 5.11 5.08 5.51 5.75 6.13 6.18 6.74 3.81 4.09 3 .65 3.92 3.57 3.82 4.12 4.49 4.36 4.50 4.69 5 .07 5.25 5.55 3 .20 3 .63 2.90 3.10 2.89 3 .50 3.36 2 .07 2 .14

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408 e* .ol. 00*0 15.

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2 p oo30 3*

O

*oo &o *o ATOM 854 N SER ATOM 855 HN SER ATOM 856 CA SER ATOM 857 HA SER ATOM 858 CB SER ATOM 859 HB1 SER ATOM 860 HB2 SER ATOM 861 OG SER ATOM 862 HG SER ATOM 863 C SER ATOM 864 0 SER ATOM 865 N TYR ATOM 866 HN TYR ATOM 867 CA TYR ATOM 868 HA TYR ATOM 869 CB TYR ATOM 870 HB1 TYR ATOM 871 HB2 TYR ATOM 872 CG TYR ATOM 873 CD1 TYR ATOM 874 HD1 TYR ATOM 875 CE1 TYR ATOM 876 HE1 TYR ATOM 877 CD2 TYR ATOM 878 HD2 TYR ATOM 879 CE2 TYR ATOM 880 HE2 TYR ATOM 881 CZ TYR ATOM 882 OH TYR ATOM 883 HH TYR ATOM 884 C TYR ATOM 885 0 TYR ATOM 886 N ALA ATOM 887 HN ALA ATOM 888 CA ALA ATOM 889 HA ALA ATOM 890 CB !ALA ATOM 891 HB1 ALA ATOM 892 HB2 ALA -3.813 1.393 11.393 1.00 1.70 -2.872 1.089 11.546 1.00 2.10 -4.246 1.842 10.081 1.00 1.20 -5.249 1.439 9.915 1.00 1.42 -4.264 3.368 10.044 1.00 1.53 -4.616 3.729 9.077 1.00 2.11 -4.924 3.768 10.813 1.00 2.00 -2.976 3.886 10.260 1.00 2.00 -3.047 4.829 10.192 1.00 2.35 -3.303 1.289 9.012 1.00 1.13 -2.209 0.816 9.294 1.00 1.26 -3.810 1.382 7.770 1.00 1.03 -4.714 1.782 7.618 1.00 1.07 -3.016 0.893 6.651 1.00 0.97 -2.326 0.140 7.042 1.00 1.03 -3.935 0.293 5.576 1.00 1.02 -4.479 1.088 5.067 1.00 1.00 -3.339 -0.221 4.822 1.00 1.04 -4.930 -0.680 6.154 1.00 1.14 -4.662 -1.349 7.375 1.00 1.94 -3.731 -1.169 7.893 1.00 2.71 -5.606 -2.250 7.919 1.00 2.04 -5.396 -2.755 8.851 1.00 2.86 -6.154 -0.927 5.486 1.00 1.46 -6.368 -0.424 4.554 1.00 2.15 -7.098 -1.828 6.030 1.00 1.54 -8.030 -2.010 5.515 1.00 2.22 -6.823 -2.489 7.246 1.00 1.40 -7.745 -3.368 7.778 1.00 1.54 -7.413 -3.721 8.593 1.00 1.79 -2.218 2.061 6.073 1.00 0.86 -2.370 3.204 6.485 1.00 0.99 -1.359 1.706 5.099 1.00 0.73 -1.271 0.753 4.808 1.00 0.79 -0.566 2.758 4.484 1.00 0.64 -1.267 3.533 4.166 1.00 0.63 0.423 3.321 5.501 1.00 0.70 1.028 4.111 5.056 1.00 1.06 -0.100 3.742 6.360 1.00 1.35

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

409 ATOM 893 HB3 ALA 51 1.096 2.545 5.864 1.00 1.32 ACSY ATOM 894 C ALA 51 0.170 2.230 3.251 1.00 0.57 ACSY ATOM 895 0 ALA 51 0.835 1.202 3.275 1.00 0.65 ACSY ATOM 896 N LEU 52 -0.001 3.026 2.179 1.00 0.47 ACSY ATOM 897 HN LEU 52 -0.580 3.841 2.248 1.00 0.49 ACSY ATOM 898 CA LEU 52 0.636 2.681 0.915 1.00 0.41 ACSY ATOM 899 HA LEU 52 0.565 1.597 0.793 1.00 0.45 ACSY ATOM 900 CB LET 52 -0-091 3.413 -0.211 1.00 0.42 ACSY ATOM 901 HB1 LEU 52 -0.946 2.821 -0.539 1.00 0.51 ACSY ATOM 902 HB2 LEU 52 -0.486 4.355 0.166 1.00 0.45 ACSY ATOM 903 CG LEU 52 0.825 3.693 -1.401 1.00 0.37 ACSY ATOM 904 HG LEU 52 1.597 4.411 -1.091 1.00 0.35 ACSY ATOM 905 CD1 LEU 52 1.502 2.404 -1.871 1.00 0.43 ACSY ATOM 906 HD11 LEU 52 1.255 1.571 -1.212 1.00 1.05 ACSY 15 ATOM 907 HD12 LEU 52 1.179 2.140 -2.879 1.00 1.13 ACSY ATOM 908 HD13 LEU 52 2.586 2.514 -1.883 1.00 1.16 ACSY ,"*ATOM 909 CD2 LEU 52 0.016 4.312 -2.537 1.00 0.42 ACSY ATOM 910 HD21 LEU 52 -0.414 5.264 -2.229 1.00 0.95 ACSY o* ATOM 911 HD22 LEU 52 0.642 4.488 -3.409 1.00 1.11 ACSY 20 ATOM 912 HD23 LEU 52 -0.801 3.655 -2.835 1.00 1.13 ACSY ATOM 913 C LEU 52 2.106 3.096 0.949 1.00 0.36 ACSY ATOM 914 0 LEU 52 2.448 4.200 1.334 1.00 0.39 ACSY ATOM 915 N CYS 53 2.947 2.145 0.501 1.00 0.38 ACSY ATOM 916 HN CYS 53 2.601 1.265 0.177 1.00 0.44 ACSY 25 ATOM 917 CA CYS 53 4.373 2.434 0.500 1.00 0.38 ACSY SATOM 918 HA CYS 53 4.490 3.501 0.712 1.00 0.40 ACSY ATOM 919 CB CYS 53 5.058 1.592 1.573 1.00 0.49 ACSY ATOM 920 HB1 CYS 53 4.979 0.535 1.318 1.00 0.73 ACSY ATOM 921 HB2 CYS 53 6.121 1.832 1.609 1.00 0.87 ACSY ATOM 922 SG CYS 53 4.353 1.841 3.222 1.00 1.14 ACSY ATOM 923 HG CYS 53 3.090 1.409 3.236 1.00 1.74 ACSY ATOM 924 C CYS 53 4.976 2.130 -0.872 1.00 0.34 ACSY ATOM 925 0 CYS 53 5.041 0.989 -1.310 1.00 0.44 ACSY ATOM 926 N LEU 54 5.419 3.230 -1.512 1.00 0.33 ACSY ATOM 927 HN LEU 54 5.333 4.135 -1.089 1.00 0.38 ACSY ATOM 928 CA LEU 54 6.035 3.068 -2.825 1.00 0.36 ACSY ATOM 929 HA LEU 54 6.309 2.013 -2.913 1.00 0.36 ACSY ATOM 930 CB LEU 54 5.054 3.452 -3.942 1.00 0.45 ACSY ATOM 931 HB1 LEU 54 5.563 3.378 -4.902 1.00 1.31 ACSY 410 ATOM 932 HB2 LEU 54 4.248 2.724 -3.965 1.00 0.57 ACSY ATOM 933 CG LEU 54 4.454 4.861 -3.799 1.00 0.42 ACSY ATOM 934 HG LEU 54 4.083 5.165 -4.779 1.00 0.72 ACSY ATOM 935 CD1 LEU 54 3.272 4.856 -2.832 1.00 0.55 ACSY ATOM 936 HD11 LEU 54 2.754 5.815 -2.849 1.00 1.22 ACSY ATOM 937 HD12 LEU 54 2.555 4.083 -3.102 1.00 1.16 ACSY ATOM 938 HD13 LEU 54 3.601 4.671 -1.811 1.00 1.05 ACSY ATOM 939 CD2 LrEU 54 5.504 5.873 -3.348 1.00 0.59 ACSY ATOM 940 HD21 LEU 54 6.391 5.824 -3.978 1.00 1.17 ACSY ATOM 941 HD22 LEU 54 5.111 6.889 -3.397 1.00 1.25 ACSY ATOM 942 HD23 LEU 54 5.806 5.679 -2.323 1.00 1.10 ACSY ATOM 943 C LEU 54 7.313 3.900 -2.883 1.00 0.43 ACSY ATOM 944 0 LEU 54 7.617 4.666 -1.980 1.00 0.49 ACSY SATOM 945 N LEU 55 8.059 3.691 -3.986 1.00 0.50 ACSY :ooo 15 ATOM 946 HN LEU 55 7.787 3.019 -4.690 1.00 0.53 ACSY ATOM 947 CA LEU 55 9.293 4.449 -4.103 1.00 0.62 ACSY i ATOM 948 HA LEU 55 9.333 5.134 -3.251 1.00 0.63 ACSY ATOM 949 CB LEU 55 10.473 3.493 -4.072 1.00 0.65 ACSY ATOM 950 HB1 LEU 55 10.385 2.842 -3.211 1.00 0.59 ACSY 20 ATOM 951 HB2 LEU 55 10.442 2.853 -4.952 1.00 0.69 ACSY ATOM 952 CG LEU 55 11.805 4.248 -4.033 1.00 0.77 ACSY ATOM 953 HG LEU 55 11.627 5.274 -4.349 1.00 0.84 ACSY o. ATOM 954 CD1 LEU 55 12.397 4.274 -2.631 1.00 0.77 ACSY ATOM 955 HD11 LEU 55 11.642 4.062 -1.883 1.00 1.27 ACSY 25 ATOM 956 HD12 LEU 55 13.190 3.534 -2.535 1.00 1.29 ACSY ATOM 957 HD13 LEU 55 12.827 5.249 -2.414 1.00 1.20 ACSY ATOM 958 CD2 LEU 55 12.802 3.605 -4.983 1.00 0.84 ACSY ATOM 959 HD21 LEU 55 12.925 2.547 -4.750 1.00 1.24 ACSY ATOM 960 HD22 LEU 55 12.468 3.690 -6.013 1.00 1.34 ACSY ATOM 961 HD23 LEU 55 13.777 4.084 -4.898 1.00 1.32 ACSY ATOM 962 C LEU 55 9.307 5.264 -5.390 1.00 0.74 ACSY ATOM 963 0 LEU 55 8.897 4.810 -6.451 1.00 0.79 ACSY ATOM 964 N HIS 56 9.811 6.501 -5.216 1.00 0.84 ACSY ATOM 965 HN HIS 56 10.099 6.815 -4.309 1.00 0.83 ACSY ATOM 966 CA HIS 56 9.899 7.379 -6.367 1.00 0.97 ACSY ATOM 967 HA HIS 56 8.998 7.214 -6.965 1.00 1.01 ACSY ATOM 968 CB HIS 56 9.974 8.830 -5.895 1.00 1.00 ACSY ATOM 969 HB1 HIS 56 9.096 9.085 -5.301 1.00 1.00 ACSY ATOM 970 HB2 HIS 56 10.853 8.985 -5.270 1.00 1.10 ACSY 411

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

20 ATOM

ATOM

ATOM

ATOM

971 972 973 974 975 976 977 978 979 980 981 982 983 984 985 986 987 988 989 990 991 992 993 *o *ooooo* *ooooo CG HIS CD2 HIS HD2 HIS ND1 HIS HD1 HIS CE1 HIS HE1 HIS NE2 HIS C HIS O HIS N GLU HN GLU CA GLU HA GLU CB GLU HB1 GLU HB2 GLU CG GLU HG1 GLU HG2 GLU CD GLU OE1 GLU OE2 GLU C GLU 0 GLU N GLY HN GLY CA GLY HA1 GLY HA2 GLY C GLY O GLY N LYS HN LYS CA LYS HA LYS CB LYS HB1 LYS HB2 LYS 10.678 11.213 9.492 8.987 9.771 9.460 10.485 11.135 11.119 12.204 12.150 13.440 13.248 13.801 14.040 14.698 12.656 11.705 12.577 12.899 12.048 13.937 14.594 15.756 14.195 13.230 15.182 16.152 15.169 14.867 15.744 13.549 12.907 13.050 13.756 12.862 11.954 12.720 10.996 -7.193 11.508 -6.408 9.456 -8.294 8.651 -8.529 10.495 -9.099 10.565 -10.131 11.437 -8.458 7.004 -7.202 6.071 -7.991 7.789 -6.970 8.542 -6.314 7.535 -7.711 6.710 -8.403 8.802 -8.459 9.577 -7.732 8.639 -9.057 9.272 -9.356 8.866 -9.011 10.357 -9.338 8.812 -10.795 8.110 -11.339 9.161 -11.355 7.156 -6.767 7.113 -7.156 6.890 -5.517 6.933 -5.286 6.535 -4.511 6.846 -4.876 5.451 -4.404 7.213 -3.169 7.559 -2.388 7.370 -2.981 7.044 -3.661 7.969 -1.778 7.745 -0.975 9.468 -1.964 9.650 -2.536 9.936 -0.990 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 2.03 2.72 1.62 2.07 1.85 2.24 2.10 1.26 2.14 1.18 1.66 1.28 1.36 1.42 1.46 1.58 1.51 1.60 1.73 1.74 2 .07 2.29 1.28 1.56 1.15 1.21 1.14 1.29 1.17 1.10 1.20 0.98 0.94 0.96 1.00 1.06 1.09 1.09 56 10.047 9.742 -7.096 1.00 1.31 ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ATOM 994 ATOM 995 ATOM 996 ATOM 997 ATOM 998 ATOM 999 ATOM 1000 ATOM 1001 ATOM 1002 ATOM 1003 ATOM 1004 ATOM 1005 ATOM 1006 ATOM 1007

ATOM

ATOM

1008 1009 412 ATOM 1010 CG LYS 59 14.055 10.106 -2.673 1.00 1.30 ATOM 1011 ATOM 1012 ATOM 1013 ATOM 1014 ATOM 1015 ATOM 1016 ATOM 1017 ATOM 1018 1 0 ATOM 1019 ATOM 1020 ATOM 1021 ATOM 1022 ATOM 1023 1 5 ATOM 1024 ATOM 1025 ATOM 1026 ATOM 1027 ATOM 1028 20 ATOM 1029 ATOM 1030 ATOM 1031 ATOM 1032 ATOM 1033 ATOM 1034 ATOM 1035 ATOM 1036 ATOM 1037 ATOM 1038 ATOM 1039 ATOM 1040 ATOM 1041 ATOM 1042 ATOM 1043 ATOM 1044 ATOM 1045 ATOM 1046 ATOM 1047 ATOM 1048 HG1 HG2

CD

HD1 HD2

CE

HE1 HE2

NZ

HZ1 HZ2 HZ3

C

0

N

HN

CA

HA

CB

HB

CG1 HG11 HG12 HG13 CG2 HG21 HG22 HG23

C

0

N

HN

CA

HA

CB

HB1 HB2

CG

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

LYS

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

VAL

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

14.129 14.977 13.932 14.530 12.897 14.385 14.363 13.721 15.739 16.406 15.986 15.790 11.723 10.697 11.819 12.690 10.630 10.224 10.972 11.963 10.982 11.681 9.991 11.269 9.955 10.351 9.037 9.697 9.616 9.941 8.370 8.204 7.285 7.710 6.641 6.023 5.976 7.710 11.154 9.624 9.999 9.161 9.785 11.287 11.169 12.112 11.674 10.933 12.570 11.796 7.291 7.603 6.338 6.150 5.584 5.206 4.437 4.058 4.933 5.759 5.285 4.139 3.308 2.376 3.544 3.146 6.499 7.393 6.186 5.437 6.965 7.604 7.796 7.167 8.534 8.492 -2.388 -2.346 -4.194 -4.552 -4.462 -4.884 nI-7 -4.627 -4.507 -4.802 -4.974 -3.475 -1.506 -2.101 -0.584 -0.142 -0.267 -1.216 0.674 0.423 2.114 2.235 2.406 2.794 0.532 0.933 1.072 -0.512 0.393 1.164 0.048 -0.570 0.591 1.366 -0.508 -1.146 -0.069 -1.323 1.00 1.00 1.00 1.00 1.00 1.00 1. 00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.73 1.75 1.40 1.77 1.75 1.71 2.09 2.06 2.39 2.76 2 .67 2.93 0 .83 0.79 0.78 0 .83 0 .66 0 .62 0.66 0.70 0.73 1.16 1.28 1.17 0.57 1.16 1.12 1 .05 0.66 0.75 0.56 0.51 0 .57 0.65 0.58 0.53 0.62 0.68

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

413 ATOM 1049 HG LEU 61 8.308 7.738 -1.835 1.00 0.66 ACSY a 0 15 20 ATOM 1050 ATOM 1051 ATOM 1052 ATOM 1053 ATOM 1054 ATOM 1055 ATOM 1056 ATOM 1057 ATOM 1058 ATOM 1059 ATOM 1060 ATOM 1061 ATOM 1062 ATOM 1063 ATOM 1064 ATOM 1065 ATOM 1066 ATOM 1067 ATOM 1068 ATOM 1069 ATOM 1070 ATOM 1071 ATOM 1072 ATOM 1073 ATOM 1074 ATOM 1075 ATOM 1076 ATOM 1077 ATOM 1078 ATOM 1079 ATOM 1080 ATOM 1081 ATOM 1082 ATOM 1083 ATOM 1084 ATOM 1085 ATOM 1086 ATOM 1087 CD1 HD11 HD12 HD13 CD2 HD21 HD22 HD23

C

0

N

HN

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

LEU

HIS

HIS

CA HIS HA HIS CB HIS HB1 HIS HB2 HIS CG HIS CD2 HIS HD2 HIS ND1 HIS HD1 HIS CE1 HIS HE1 HIS NE2 HIS C HIS 0 HIS N TYR HN TYR CA TYR HA TYR 7.090 7.859 6.552 6.389 8.609 8.692 8.209 9.605 6.252 6.206 5.422 5.550 4.350 4.120 4.795 4.885 4.058 6.135 7.412 7.634 6.288 5.578 7.611 8.058 8.308 3 .122 3 .223 1 .961 1. 939 0 .733 0 .957 0 .182 0 .152 -0.831 1.010 1.729 1.670 2.514 9.413 9.995 8.835 10.109 9.268 10.304 9.248 8.834 6.080 4.868 6.800 7.798 6.118 5.215 5.762 6.663 5 .117 5 .049 5.625 6.678 3.709 3 .043 3 .471 2 .487 4 .612 7 .030 8 .236 6 .378 5.396 7.136 8.138 7 177 6.170 7.543 8.044 7.461 6.403 8.256 -2.368 -2.878 -3.117 -1.908 -0.376 -0.682 0.639 -0.350 1.228 1 .051 1 .975 2 .044 2 .676 2 .103 4 .102 4.708 4.581 4 .069 3 .932 3 .835 4 .159 4.263 4.080 4.121 3.942 2.698 2.842 2.529 2.393 2.531 2.910 1.114 0.699 1.129 0 .211 -0.860 -1.030 -1.715 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0.75 1.33 1.20 1.22 0.78 1.25 1.39 1.15 0.50 0.47 0.51 0.57 0.51 0.44 0.64 0.73 0.73 0.68 1.28 1.97 0.98 1.60 0.81 1.04 1.17 0.53 0.81 0.51 0.72 0.52 0.55 0.47 0.93 0.77 0.45 1.28 2.17 1.28

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

CB

HB1 HB2

CG

CD1 HD1 CE1

TYR

TYR

TYR

TYR

TYR

TYR

TYR

414

ATOM

ATOM

1088 1089 15 20 ATOM 1090 ATOM 1091 ATOM 1092 ATOM 1093 ATOM 1094 ATOM 1095 ATOM 1096 ATOM 1097 ATOM 1098 ATOM 1099 ATOM 1100 ATOM 1101 ATOM 1102 ATOM 1103 ATOM 1104 ATOM 1105 ATOM 1106 ATOM 1107 ATOM 1108 ATOM 1109 ATOM 1110 ATOM 1111 ATOM 1112 ATOM 1113 ATOM 1114 ATOM 1115 ATOM 1116 ATOM 1117 HE1 TYR CD2 TYR HD2 TYR CE2 TYR HE2 TYR CZ TYR OH TYR HH TYR C TYR O TYR N ARG HN ARG CA ARG HA ARG CB ARG HB1 ARG HB2 ARG CG ARG HG1 ARG HG2 ARG CD ARG HD1 ARG HD2 ARG NE ARG HE ARG CZ ARG NH1 ARG HH11 ARG HH12 ARG NH2 ARG 1.089 9.446 0.540 9.915 1.877 10.240 1.947 11.294 2.589 9.648 3.359 10.430 3.797 9.878 -0.273 6.447 -0.650 5.306 -0.695 7.211 -0.363 8.147 -1.658 6.634 -1.238 5.684 -1.914 7.570 -2.959 7.495 -1.325 7.240 -1.584 9.028 -0.504 9.170 -1.929 9.258 -2.234 9.991 -1.823 9.873 -3.312 9.850 -2.007 11.366 -2.669 11.842 -0.886 11.990 -0.655 13.248 -1.313 13.730 0.176 13.712 -0.010 11.350 -0.181 10.404 0.821 11.816 -2.958 6.358 -3.435 7.160 -3.492 5.169 -3.032 4.563 -4.732 4.777 -5.128 5.657 -4.436 3.661 3.059 7.796 -2.524 1.00 2.14 ACSY 1.216 -0.446 -0.276 -1.510 -2.347 -2.982 3.445 3.228 4.466 4.582 5.389 5.739 6.566 6.864 7.418 6.234 6.237 5.226 7.228 8.231 7.277 6.820 6.242 7.232 6.869 6.290 7.174 8.002 8.276 8.306 4.645 3 .852 4.959 5.603 4.314 3.800 3.325 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0.412 1.00 1.28 2.15 1.33 2.22 0.58 0.68 1.05 0.60 0.80 0.59 0.65 0.67 0.70 0.72 1.09 1.24 1.73 2.39 2.33 1.95 2.17 2.56 2.22 2.64 2.59 3.34 3.74 3.75 2.83 2.84 3.37 0.74 1.34 0.74 1.15 0.78 0.75 0.81

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1118 HH21 ARG 1119 HH22 ARG 1120 C ARG 1121 O ARG 1122 N ILE 1123 HN ILE 1124 CA ILE 1125 HA ILE 1126 CB ILE 415 ATOM 1127 HB ILE 65 -3.710 2.983 3.779 1.00 0.81 ACSY ATOM 1128 CG2 ILE 65 -5.704 2.870 3.001 1.00 1.05 ACSY ATOM 1129 HG21 ILE 65 -6.468 3.519 2.573 1.00 1.66 ACSY ATOM 1130 HG22 ILE 65 -5.495 2.077 2.283 1.00 1.37 ACSY ATOM 1131 HG23 ILE 65 -6.117 2.411 3.899 1.00 1.48 ACSY ATOM 1132 CGI ILE 65 -3.831 4.228 2.051 1.00 0.82 ACSY ATOM 1133 HGII ILE 65 -4.622 4.508 1.357 1.00 1.30 ACSY 134 I 12 ILE 65 -3.272 5.135 2.281 1.00 1.25 ACSY ATOM 1135 CD1 ILE 65 -2.911 3.207 1.403 1.00 0.86 ACSY ATOM 1136 HDII ILE 65 -3.485 2.448 0.875 1.00 1.50 ACSY ATOM 1137 HD12 ILE 65 -2.243 3.684 0.692 1.00 1.23 ACSY ATOM 1138 HD13 ILE 65 -2.305 2.705 2.157 1.00 1.39 ACSY ATOM 1139 C ILE 65 -5.757 4.295 5 .339 1.00 0.96 ACSY ATOM 1140 0 ILE 65 -5.561 3.310 6.040 1.00 1.18 ACSY ATOM 1141 N ASP 66 -6.863 5.059 5.367 1.00 0.95 ACSY ATOM 1142 HN ASP 66 -6.934 5.874 4.797 1.00 0.90 ACSY ATOM 1143 CA ASP 66 -7.942 4.692 6.257 1.00 1.13 ACSY ATOM 1144 RA ASP 66 -7.945 3.602 6.335 1.00 1.31 ACSY ATOM 1145 CB ASP 66 -7.759 5.335 7.618 1.00 1.41 ACSY ATOM 1146 HB1 ASP 66 -6.738 5.221 7.963 1.00 1.63 ACSY ATOM 1147 HB2 ASP 66 -7.981 6.395 7.560 1.00 1.51 ACSY ATOM 1148 CG ASP 66 -8.703 4.684 8.631 1.00 1.74 ACSY ATOM 1149 ODI ASP 66 -8.651 3.465 8 .783 1.00 2.12 ACSY ATOM 1150 OD2 ASP 66 -9.478 5.405 9.258 1.00 2.27 ACSY ATOM 1151 C ASP 66 -9.252 5.150 5 .645 1.00 1.07 ACSY ATOM 1152 0 ASP 66 -9.294 5.809 4.617 1.00 1.32 ACSY ATOM 1153 N LYS 67 -10.308 4.788 6.373 1.00 1.25 ACSY ATOM 1154 HN LYS 67 -10.183 4.303 7.235 1.00 1.58 ACSY ATOM 1155 CA LYS 67 -11.628 5.141 5 .899 1.00 1.22 ACSY ATOM 1156 HA LYS 67 -11.573 5.207 4.808 1.00 1.15 ACSY ATOM 1157 CB LYS 67 -12.617 4.064 6.335 1.00 1.34 ACSY ATOM 1158 HB1 LYS 67 -13.618 4.324 5.992 1.00 1.51 ACSY ATOM 1159 HB2 LYS 67 -12.359 3.114 5.867 1.00 1.51 ACSY ATOM 1160 CG LYS 67 -12.623 3.907 7.851 1.00 1.53 ACSY ATOM 1161 HG1 LYS 67 -12.083 4.738 8.301 1.00 2.00 ACSY ATOM 1162 HG2 LYS 67 -13.641 3 .962 8.219 1.00 1.67 ACSY ATOM 1163 CD LYS 67 -11.994 2.582 8.283 1.00 1.92 ACSY ATOM 1164 HD1 LYS 67 -11.023 2.464 7.803 1.00 2.32 ACSY ATOM 1165 HD2 LYS 67 -11.816 2 .596 9.357 1.00 2.35 ACSY 416 ATOM 1166 CE LYS 67 -12.889 1.395 7.929 1.00 2.17 oooo: oo ATOM 1167 ATOM 1168 ATOM 1169 ATOM 1170 ATOM 1171 ATOM 1172 ATOM 1173 ATOM 1174 1 0 ATOM 1175 ATOM 1176 ATOM 1177 ATOM 1178 ATOM 1179 1 5 ATOM 1180 ATOM 1181 ATOM 1182 ATOM 1183 ATOM 1184 ATOM 1185 ATOM 1186 ATOM 1187 ATOM 1188 ATOM 1189 ATOM 1190 ATOM 1191 ATOM 1192 ATOM 1193 ATOM 1194 ATOM 1195 ATOM 1196 ATOM 1197 ATOM 1198 ATOM 1199 ATOM 1200 ATOM 1201 ATOM 1202 ATOM 1203 ATOM 1204 HE1 LYS HE2 LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS O LYS N ASP HN ASP CA ASP HA ASP CB ASP HB1 ASP HB2 ASP CG ASP OD1 ASP OD2 ASP C ASP O ASP N LYS HN LYS CA LYS HA LYS CB LYS HB1 LYS HB2 LYS CG LYS HG1 LYS HG2 LYS CD LYS HD1 LYS HD2 LYS CE LYS HE1 LYS HE2 LYS NZ LYS HZ1 LYS -13.820 -13.144 -12.252 -11.401 -11.986 -12.915 -12.033 -11.204 -13.364 -13.980 -13.896 -13.129 -14.254 -14.300 -15.230 -13.205 -12.020 -13.586 -15.134 -16.196 -14.920 -14.018 -16.030 -15.737 -16.293 -16.568 -17.140 -15.066 -14.395 -15.371 -14.323 -15.023 -13.917 -13.191 -12.472 -13.583 -12.467 -13. 126 1.435 1.409 0.115 0.013 0.076 -0.658 6.501 7.351 6.639 5.895 7.882 8.329 8.797 8.231 9.250 9.902 9.607 11.046 7.572 8.158 6.607 6.186 6.185 5 .232 7.239 8 .182 6.933 7 .443 8.167 7.864 6.127 5.368 5.769 6 .287 7 .032 6.620 5.041 4.316 8.495 6.870 8.214 7.626 9.219 8.001 6 464 6.768 6.581 6.309 7.105 7.741 5.942 5 .011 6.101 5.804 5 .945 5 .557 7 .938 7 .766 8 .848 8 .942 9 .693 10.143 10.764 10.293 11.377 11.650 11.187 12.608 11.878 12.226 10.930 12.893 12.552 13.854 13.117 13.466 1.00 1.00 1.00 1.00 1.00 1.00 1.00n 1 AA 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1.00 1 00 1 .00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 2.50 2.34 2.57 2.87 3.05 2.72 1.37 1.56 1.41 1.41 1.62 1.70 1.72 1.61 2.02 1.96 2.32 2.39 1.77 2.22 1.68 1.77 1.82 1.87 2.01 2 .15 2 .17 2 .50 2.75 2.88 3 .02 3 .24 3.05 3 .77 4.07 4.08 4.38 4.70

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY.

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

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ACSY

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ACSY

417 ATOM 1205 HZ2 LYS 69 -12.042 4.722 12.224 1.00 4.59 ACSY ATOM 1206 HZ3 LYS 69 -11.718 5.198 13.822 1.00 4.74 ACSY ATOM 1207 C LYS 69 -17.277 5.944 8.837 1.00 1.81 ACSY ATOM 1208 0 LYS 69 -18.411 6.099 9.273 1.00 2.01 ACSY ATOM 1209 N THR 70 -16.968 5.553 7.593 1.00 1.66 ACSY ATOM 1210 HN THR 70 -16.014 5.483 7.311 1.00 1.60 ACSY ATOM 1211 CA THR 70 -18.004 5.255 6.645 1.00 1.68 ACSY ATOM 1212 HA THR 70 -18.964 5.528 7.089 1-00 1.83 ACSY ATOM 1213 CB THR 70 -17.709 6.052 5.385 1.00 1.63 ACSY ATOM 1214 HB THR 70 -16.640 6.255 5.341 1.00 1.55 ACSY ATOM 1215 OG1 THR 70 -18.371 7.291 5.441 1.00 1.81 ACSY ATOM 1216 HG1 THR 70 -19.295 7.103 5.531 1.00 1.95 ACSY ATOM 1217 CG2 THR 70 -18.118 5.300 4.130 1.00 1.62 ACSY ATOM 1218 HG21 THR 70 -17.566 4.363 4.051 1.00 1.96 ACSY 15 ATOM 1219 HG22 THR 70 -19.180 5.066 4.149 1.00 1.86 ACSY ATOM 1220 HG23 THR 70 -17.911 5.891 3.241 1.00 1.91 ACSY ATOM 1221 C THR 70 -17.968 3.755 6.336 1.00 1.67 ACSY ATOM 1222 0 THR 70 -18.974 3.128 6.025 1.00 1.79 ACSY ATOM 1223 N GLY 71 -16.728 3.235 6.447 1.00 1.59 ACSY oo 20 ATOM 1224 HN GLY 71 -15.964 3.809 6.749 1.00 1.53 ACSY e ATOM 1225 CA GLY 71 -16.532 1.833 6.169 1.00 1.67 ACSY ATOM 1226 HA1 GLY 71 -17.512 1.401 6.014 1.00 1.80 ACSY ATOM 1227 HA2 GLY 71 -16.075 1.396 7.050 1.00 1.79 ACSY o ATOM 1228 C GLY 71 -15.651 1.599 4.933 1.00 1.52 ACSY ATOM 1229 0 GLY 71 -15.118 0.517 4.717 1.00 1.62 ACSY ATOM 1230 N LYS 72 -15.539 2.681 4.146 1.00 1.36 ACSY ATOM 1231 HN LYS 72 -15.986 3.536 4.401 1.00 1.37 ACSY ATOM 1232 CA LYS 72 -14.737 2.586 2.939 1.00 1.28 ACSY ATOM 1233 HA LYS 72 -14.667 1.528 2.679 1.00 1.36 ACSY ATOM 1234 CB LYS 72 -15.400 3.380 1. 816 1.00 1.29 ACSY ATOM 1235 HB1 LYS 72 -15.365 4.444 2.053 1.00 1.38 ACSY ATOM 1236 HB2 LYS 72 -14.836 3.246 0.893 1.00 1.42 ACSY ATOM 1237 CG LYS 72 -16.851 2.951 1.599 1.00 1.65 ACSY ATOM 1238 HG1 LYS 72 -16.890 1.883 1.387 1.00 1.80 ACSY ATOM 1239 HG2 LYS 72 -17.421 3.112 2.513 1.00 1.99 ACSY ATOM 1240 CD LYS 72 -17.496 3.727 0.450 1.00 2.27 ACSY ATOM 1241 HD1 LYS 72 -17.213 4.778 0.515 1.00 2.73 ACSY ATOM 1242 HD2 LYS 72 -17.114 3.357 -0.502 1.00 2.64 ACSY ATOM 1243 CE LYS 72 -19.020 3.605 0.475 1.00 2.74 ACSY 418 ATOM 1244 HE1 LYS 72 -19.321 2.558 0.439 1.00 2.96 ACSY ATOM 1245 HE2 LYS 72 -19.422 4.035 1.392 1.00 3.17 ACSY ATOM 1246 NZ LYS 72 -19.651 4.286 -0.649 1.00 3.27 ACSY ATOM 1247 HZ1 LYS 72 -20.686 4.215 -0.561 1.00 3.63 ACSY ATOM 1248 HZ2 LYS 72 -19.371 5.289 -0.648 1.00 3.46 ACSY ATOM 1249 HZ3 LYS 72 -19.346 3.842 -1.539 1.00 3.62 ACSY ATOM 1250 C LYS 72 -13.342 3.128 3.221 1.00 1.20 ACSY ATOM 1251 0 LYS 72 -13.170 4.120 3.912 1.00 1.30 ACSY ATOM 1252 N LEU 73 -12.363 2.429 2.621 1.00 1.12 ACSY ATOM 1253 HN LEU 73 -12.573 1.653 2.026 1.00 1.17 ACSY ATOM 1254 CA LEU 73 -10.994 2.851 2.828 1.00 1.07 ACSY ATOM 1255 HA LEU 73 -10.894 3.156 3.878 1.00 1.09 ACSY ATOM 1256 CB LEU 73 -10.049 1.701 2.490 1.00 1.07 ACSY •*ATOM 1257 HB1 LEU 73 -10.307 1.293 1.513 1.00 1.23 ACSY oo 1 5 ATOM 1258 HB2 LEU 73 -9.034 2.080 2.411 1.00 1.08 ACSY ATOM 1259 CG LEU 73 -10.098 0.587 3.536 1.00 1.12 ACSY ATOM 1260 HG LEU 73 -11.121 0.215 3.600 1.00 1.31 ACSY ATOM 1261 CD1 LEU 73 -9.187 -0.567 3.120 1.00 1.13 ACSY ATOM 1262 HD11 LEU 73 -9.263 -1.397 3.822 1.00 1.55 ACSY o 20 ATOM 1263 HD12 LEU 73 -9.455 -0.937 2.130 1.00 1.77 ACSY o* g ATOM 1264 HD13 LEU 73 -8.145 -0.248 3.087 1.00 1.22 ACSY ATOM 1265 CD2 LEU 73 -9.680 1.120 4.909 1.00 1.21 ACSY •'ATOM 1266 HD21 LEU 73 -8.705 1.606 4.858 1.00 1.53 ACSY ATOM 1267 HD22 LEU 73 -10.400 1.848 5.281 1.00 1.71 ACSY ATOM 1268 HD23 LEU 73 -9.615 0.311 5.637 1.00 1.59 ACSY ATOM 1269 C LEU 73 -10.716 4.044 1.924 1.00 1.03 ACSY SATOM 1270 0 LEU 73 -11.383 4.262 0.923 1.00 1.10 ACSY ATOM 1271 N SER 74 -9.696 4.802 2.346 1.00 0.98 ACSY ATOM 1272 HN SER 74 -9.199 4.574 3.184 1.00 1.00 ACSY ATOM 1273 CA SER 74 -9.350 5.969 1.562 1.00 0.95 ACSY ATOM 1274 HA SER 74 -9.233 5.644 0.524 1.00 0.94 ACSY ATOM 1275 CB SER 74 -10.470 6.999 1.685 1.00 1.02 ACSY ATOM 1276 HB1 SER 74 -10.201 7.925 1.180 1.00 1.48 ACSY ATOM 1277 HB2 SER 74 -11.392 6.626 1.240 1.00 1.56 ACSY ATOM 1278 OG SER 74 -10.724 7.295 3.035 1.00 1.35 ACSY ATOM 1279 HG SER 74 -11.419 7.940 3.046 1.00 1.36 ACSY ATOM 1280 C SER 74 -8.034 6.564 2.052 1.00 0.91 ACSY ATOM 1281 0 SER 74 -7.308 5.984 2.851 1.00 1.21 ACSY ATOM 1282 N ILE 75 -7.792 7.766 1.507 1.00 0.80 ACSY 419 ATOM 1283 HN ILE 75 -8.442 8.166 0.861 1.00 0.98

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ATOM

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ATOM

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15 ATOM

ATOM

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ATOM

20 ATOM

ATOM

ATOM

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ATOM

1284 CA ILE 1285 HA ILE 1286 CB ILE 1287 HB ILE 1288 CG2 ILE 1289 HG21 ILE 1290 HG22 ILE 1291 HG23 ILE 1292 CG1 ILE 1293 HGII ILE 1294 HG12 ILE 1295 CD1 ILE 1296 HDII ILE 1297 HD12 ILE 1298 HD13 ILE 1299 1300 1301 1302 1303 1304 1305 1306 1307 1308 1309 1310 1311 1312 1313 1314 1315 1316 1317 1318 1319 1320 1321 C ILE O ILE N PRO CD PRO HDI PRO HD2 PRO CA PRO HA PRO CB PRO HB1 PRO HB2 PRO CG PRO HG1 PRO HG2 PRO C PRO 0 PRO N GLU HN GLU CA GLU HA GLU CB GLU HBI GLU HB2 GLU -6.581 -6.269 -5.511 -5.938 -4.287 -3.615 -3.727 -4.581 -5.094 -4.812 -5.941 -3.925 -3.027 -3.698 -4.158 -6.906 -7.672 -6.283 -5.351 -4.570 -5.872 -6.467 -7.478 -5.437 -4.694 -5.921 -4.770 -3.689 974 -6.239 151 962 -4.273 -4.600 197 111 -2.533 859 8.479 8.131 8.203 8.425 9.097 8.669 9.215 10.088 6.733 6.448 6.107 6.473 6.991 5.409 6.822 9.973 i0.490 10.643 10.026 9.501 9.307 12.066 12.256 12.470 13.143 12.993 11.176 11.230 11.023 12.842 13.420 12.809 12.329 13.494 14.409 13.821 12.905 1.864 2.851 0.808 -0.169 1.016 1.759 0.089 1.359 0.832 1.845 0.553 -0.121 0.216 -0.178 -1.127 1.916 1.113 2.910 3 .835 3.288 4.466 3 .108 3 .461 4.167 3 .740 4.991 4.664 4.540 5.724 1. 812 1.232 1.408 1.948 0.178 0.128 0.209 0.084 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1. 00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0.76 0.79 0.72 1.16 0.90 1.48 1.34 1.53 0.90 1.14 1.40 0.83 1.20 1.33 1.27 0.81 0.86 0.84 0.85 0.92 0.94 0.92 1.01 0.95 0.94 1.05 0.93 0.92 1.02 0.90 1.03 0.82 0.80 0.84 0.96 0.90 1.16

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14.468 -0.631 1.00 1.24 420 ATOM 1322 CG GLU 77 -2.715 14.500 1.520 1.00 1.34 ACSY ATOM 1323 HG1 GLU 77 -3.014 13.892 2.373 1.00 1.86 ACSY ATOM 1324 HG2 GLU 77 -1.636 14.637 1.571 1.00 1.80 ACSY ATOM 1325 CD GLU 77 -3 396 15.867 1.621 1.00 2.06 ACSY ATOM 1326 OE1 GLU 77 -4.001 16.145 2.655 1.00 2.62 ACSY ATOM 1327 OE2 GLU 77 -3.313 16.636 0.665 1.00 2.79 ACSY ATOM 1328 C GLU 77 -4.931 12.612 -1.035 1.00 0.73 ACSY ATOM 1329 0 GLU 77 -5-307 13.094 -2.097 1.00 0.84 ACSY ATOM 1330 N GLY 78 -4.766 11.293 -0.802 1.00 0.65 ACSY ATOM 1331 HN GLY 78 -4.457 10.971 0.091 1.00 0.74 ACSY ATOM 1332 CA GLY 78 -5.037 10.353 -1.876 1.00 0.58 ACSY ATOM 1333 HA1 GLY 78 -4.888 9.351 -1.483 1.00 0.95 ACSY ATOM 1334 HA2 GLY 78 -4.305 10.533 -2.663 1.00 0.69 ACSY ATOM 1335 C GLY 78 -6.463 10.510 -2.413 1.00 0.70 ACSY 1 5 ATOM 1336 0 GLY 78 -6.861 11.564 -2.893 1.00 0.97 ACSY ATOM 1337 N LYS 79 -7.198 9.386 -2.295 1.00 0.65 ACSY ATOM 1338 HN LYS 79 -6.806 8.558 -1.895 1.00 0.71 ACSY ATOM 1339 CA LYS 79 -8.568 9.395 -2.775 1.00 0.74 ACSY ATOM 1340 HA LYS 79 -8.879 10.435 -2.871 1.00 0.82 ACSY ATOM 1341 CB LYS 79 -8.617 8.689 -4.129 1.00 0.75 ACSY ATOM 1342 HB1 LYS 79 -7.683 8.833 -4.647 1.00 0.96 ACSY ATOM 1343 HB2 LYS 79 -8.719 7.617 -3.972 1.00 0.88 ACSY

C

ATOM 1344 CG LYS 79 -9.764 9.200 -4.998 1.00 1.02 ACSY ATOM 1345 HG1 LYS 79 -10.152 8.384 -5.607 1.00 1.25 ACSY ATOM 1346 HG2 LYS 79 -10.584 9.539 -4.365 1.00 1.14 ACSY SATOM 1347 CD LYS 79 -9.303 10.342 -5.904 1.00 1.32 ACSY SATOM 1348 HD1 LYS 79 -9.106 11.229 -5.303 1.00 1.40 ACSY ATOM 1349 HD2 LYS 79 -8.360 10.069 -6.381 1.00 1.43 ACSY ATOM 1350 CE LYS 79 -10.344 10.668 -6.976 1.00 1.64 ACSY ATOM 1351 HE1 LYS 79 -10.553 9.789 -7.586 1.00 1.84 ACSY ATOM 1352 HE2 LYS 79 -11.281 10.983 -6.517 1.00 1.93 ACSY ATOM 1353 NZ LYS 79 -9.905 11.734 -7.868 1.00 2.44 ACSY ATOM 1354 HZ1 LYS 79 -9.728 12.597 -7.316 1.00 2.79 ACSY ATOM 1355 HZ2 LYS 79 -9.030 11.444 -8.350 1.00 2.96 ACSY ATOM 1356 HZ3 LYS 79 -10.644 11.920 -8.575 1.00 2.83 ACSY ATOM 1357 C LYS 79 -9.481 8.689 -1.770 1.00 0.85 ACSY ATOM 1358 0 LYS 79 -9.352 8.823 -0.561 1.00 1.10 ACSY ATOM 1359 N LYS 80 -10.405 7.932 -2.379 1.00 0.88 ACSY ATOM 1360 HN LYS 80 -10.416 7.887 -3.381 1.00 1.00 ACSY 421 ATOM 1361 CA LYS 80 -11.366 7.178 -1.581 1.00 0.95

ACSY

ATOM 1362 HA LYS 80 -10.863 6.883 -0.657 1.00 0.94 ACSY ATOM 1363 CB LYS 80 -12.586 8.049 -1.285 1.00 1.07 ACSY ATOM 1364 HB1 LYS 80 -12.873 8.595 -2.183 1.00 1.37 ACSY ATOM 1365 HB2 LYS 80 -13.431 7.413 -1.020 1.00 1.48 ACSY ATOM 1366 CG LYS 80 -12.314 9.034 -0.148 1.00 1.96 ACSY ATOM 1367 HG1 LYS 80 -11.456 9.658 -0.400 1.00 2.60 ACSY ATOM 1368 HG2 LYS 80 -12.049 8.485 0.755 1.00 2.58 ACSY ATOM 1369 CD LYS 80 -13.528 9.919 0.133 1.00 2.13 ACSY ATOM 1370 HD1 LYS 80 -13.769 10.504 -0.755 1.00 2.69 ACSY ATOM 1371 HD2 LYS 80 -14.396 9.294 0.342 1.00 2.42 ACSY ATOM 1372 CE LYS 80 -13.276 10.858 1.313 1.00 2.10 ACSY ATOM 1373 HE1 LYS 80 -12.978 10.293 2.195 1.00 2.30 ACSY o. S ATOM 1374 HE2 LYS 80 -12.473 11.558 1.081 1.00 2.28 ACSY 1 5 ATOM 1375 NZ LYS 80 -14.457 11.638 1.664 1.00 2.59 ACSY S**o ATOM 1376 HZ1 LYS 80 -14.752 12.210 0.847 1.00 2.95 ACSY ATOM 1377 HZ2 LYS 80 -15.229 10.996 1.934 1.00 2.99 ACSY ATOM 1378 HZ3 LYS 80 -14.233 12.266 2.463 1.00 2.80 ACSY ATOM 1379 C LYS 80 -11.777 5.923 -2.354 1.00 0.98 ACSY 20 ATOM 1380 0 LYS 80 -12.191 5.986 -3.505 1.00 1.01 ACSY .4o.

ATOM 1381 N PHE 81 -11.632 4.782 -1.649 1.00 1.00 ACSY ATOM 1382 HN PHE 81 -11.275 4.790 -0.723 1.00 1.02 ACSY ATOM 1383 CA PHE 81 -11.970 3.532 -2.289 1.00 1.05 ACSY ATOM 1384 HA PHE 81 -12.605 3.760 -3.149 1.00 1.08 ACSY 25 ATOM 1385 CB PHE 81 -10.678 2.874 -2.724 1.00 1.00 ACSY SATOM 1386 HB1 PHE 81 -9.970 2.868 -1.899 1.00 0.95 ACSY ATOM 1387 HB2 PHE 81 -10.863 1.847 -2.995 1.00 1.07 ACSY ATOM 1388 CG PHE 81 -10.071 3.595 -3.889 1.00 0.97 ACSY ATOM 1389 CD1 PHE 81 -9.065 4.571 -3.683 1.00 1.42 ACSY ATOM 1390 HD1 PHE 81 -8.730 4.796 -2.680 1.00 2.20 ACSY ATOM 1391 CD2 PHE 81 -10.501 3.310 -5.207 1.00 1.66 ACSY ATOM 1392 HD2 PHE 81 -11.268 2.569 -5.373 1.00 2.45 ACSY ATOM 1393 CE1 PHE 81 -8.495 5.250 -4.784 1.00 1.43 ACSY ATOM 1394 HE1 PHE 81 -7.727 5.992 -4.621 1.00 2.17 ACSY ATOM 1395 CE2 PHE 81 -9.931 3.990 -6.307 1.00 1.72 ACSY ATOM 1396 HE2 PHE 81 -10.266 3.769 -7.310 1.00 2.54 ACSY ATOM 1397 CZ PHE 81 -8.928 4.960 -6.096 1.00 1.07 ACSY ATOM 1398 HZ PHE 81 -8.493 5.479 -6.936 1.00 1.15 ACSY ATOM 1399 C PHE 81 -12.721 2.604 -1.331 1.00 1.12 ACSY 422 4 4* *4*4 ATOM 1400 0 PHE ATOM 1401 N ASP ATOM 1402 HN ASP ATOM 1403 CA ASP ATOM 1404 HA ASP ATOM 1405 CB ASP ATOM 1406 HB1 ASP ATOM 1407 HB2 ASP ATOM 1408 CG ASP ATOM 1409 OD1 ASP ATOM 1410 OD2 ASP ATOM 1411 C ASP ATOM 1412 0 ASP ATOM 1413 N THR 1 5 ATOM 1414 HN THR ATOM 1415 CA THR ATOM 1416 HA THR ATOM 1417 CB THR ATOM 1418 HB THR ATOM 1419 OG1 THR ATOM 1420 HG1 THR ATOM 1421 CG2 THR ATOM 1422 HG21 THR ATOM 1423 HG22 THR ATOM 1424 HG23 THR ATOM 1425 C THR ATOM 1426 0 THR ATOM 1427 N LEU ATOM 1428 HN LEU ATOM 1429 CA LEU ATOM 1430 HA LEU ATOM 1431 CB LEU ATOM 1432 HB1 LEU ATOM 1433 HB2 LEU ATOM 1434 CG LEU ATOM 1435 HG LEU ATOM 1436 CD1 LEU ATOM 1437 HD11 LEU ATOM 1438 HD12 LEU -12.887 2.872 -0.144 1.00 1.13 -13.144 1.480 -1.942 1.00 1.17 -12.957 1.330 -2.913 1.00 1.17 -13.872 0.491 -1.169 1.00 1.25 -14.572 1.031 -0.524 1.00 1.29 -14.617 -0.448 -2.114 1.00 1.33 -15.388 0.091 -2.665 1.00 1.38 -13.932 -0.883 -2.842 1.00 1.29 -15.273 -1.576 -1.315 1.00 1.43 -15.202 -2.724 -1.753 1.00 1.70 -15.845 -1.295 -0.263 1.00 1.95 -12.895 -0.295 -0.299 1.00 1.22 -13.065 -0.421 0.908 1.00 1.25 -11.861 -0.814 -0.990 1.00 1.16 -11.765 -0.669 -1.977 1.00 1.14 -10.873 -1.579 -0.271 1.00 1.13 -10.875 -1.227 0.764 1.00 1.14 -11.217 -3.065 -0.348 1.00 1.21 -10.445 -3.644 0.155 1.00 1.26 -11.227 -3.472 -1;694 1.00 1.23 -12.129 -3.431 -1.985 1.00 1.47 -12.573 -3.368 0.289 1.00 1.25 -13.376 -2.863 -0.246 1.00 1.46 -12.779 -4.439 0.274 1.00 1.73 -12.598 -3.035 1.327 1.00 1.64 -9.515 -1.308 -0.894 1.00 1.03 -9.391 -0.643 -1.915 1.00 1.00 -8.510 -1.867 -0.215 1.00 1.00 -8.666 -2.396 0.613 1.00 1.05 -7.173 -1.699 -0.685 1.00 0.92 -6.979 -0.632 -0.760 1.00 0.87 -6.299 -2.389 0.330 1.00 0.92 -6.898 -3.093 0.909 1.00 1.00 -5.574 -2.978 -0.193 1.00 0.92 -5.622 -1.416 1.282 1.00 0.90 -6.380 -0.995 1.944 1.00 1.16 -4.601 -2.162 2.132 1.00 1.20 -5.101 -2.819 2.845 1.00 1.68 -3.953 -2.777 1.508 1.00 1.60

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

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ACSY

ACSY

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ACSY

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ACSY

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ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

423 ATOM 1439 HD13 LEU 84 -3.977 -1.469 2.691 1.00 1.73

S

ATOM 1440 ATOM 1441 ATOM 1442 ATOM 1443 ATOM 1444 ATOM 1445 ATOM 1446 ATOM 1447 1 0 ATOM 1448 ATOM 1449 ATOM 1450 ATOM 1451 ATOM 1452 1 5 ATOM 1453 ATOM 1454 ATOM 1455 ATOM 1456 ATOM 1457 ATOM 1458 ATOM 1459 ATOM 1460 ATOM 1461 ATOM 1462 ATOM 1463 ATOM 1464 ATOM 1465 ATOM 1466 ATOM 1467 ATOM 1468 ATOM 1469 ATOM 1470 ATOM 1471 ATOM 1472 ATOM 1473 ATOM 1474 ATOM 1475 ATOM 1476 ATOM 1477 CD2 LEU HD21 LEU HD22 LEU HD23 LEU C LEU O LEU N TRP HN TRP CA TRP HA TRP CB TRP HB1 TRP HB2 TRP CG TRP CD2 TRP CE2 TRP CE3 TRP HE3 TRP CD1 TRP HD1 TRP NE1 TRP HE1 TRP CZ2 TRP HZ2 TRP CZ3 TRP HZ3 TRP CH2 TRP HH2 TRP C TRP 0 TRP N GLN HN GLN CA GLN HA GLN CB GLN HB1 GLN HB2 GLN CG GLN -4.961 -0.278 -4.200 0.211 -4.487 -0.651 -5.696 0.474 -6.960 -2-336 -5.899 -2.237 -8.028 -2.982 -8.873 -2.979 -7.958 -3.636 -6.931 -3.986 -8.967 -4.771 -9.517 -4.792 -9.691 -4.617 -8.258 -6.083 -8.087 -7.145 -7.350 -8.172 -8.487 -7.308 -9.044 -6.530 -7.640 -6.471 -7.597 -5.877 -7.098 -7.716 -6.609 -8.212 -7.024 -9.348 -6.467 -10.122 -8.160 -8.505 -8.467 -8.640 -7.428 -9.526 -7.178 -10.437 -8.303 -2.649 -7.844 -2.737 -9.143 -1.707 -9.435 -1.683 -9.564 -0.712 -9.489 -1.171 -10.992 -0.263 -11.019 0.247 -11.314 0.460 -11.960 -1.446 0.507 1.112 -0.400 0.220 -2.056 -2.648 -2.507 -1.975 -3.800 -3.945 -3.822 -2.885 -4.622 -4.046 -3.107 -3.774 -1.787 -1.287 -5.232 -6.135 -5.073 -5.762 -3.110 -3.618 -1.100 -0.074 -1.763 -1.240 -4.891 -6.023 -4.468 -3.501 -5.420 -6.403 -5.119 -4.157 -5.868 -5.099 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0.96 1.46 1.33 1.56 0.91 0.84 1.00 1.06 1.02 0.97 1.13 1.18 1.17 1.14 1.33 1.26 1.64 1.71 1.08 1.13 1.10 1.10 1.47 1.42 1.91 2.21 1.81 2.03 1.01 1.00 1.04 1.05 1.05 1.08 1.15 1.16 1.18 1.24

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

424

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1478 HG1 GLN 1479 HG2 GLN 1480 CD GLN 1481 OE1 GLN 1482 NE2 GLN 1483 HE21 GLN 1484 HE22 GLN I AnS 1485 C GLN 1486 0 GLN 1487 N LEU 1488 HN LEU 1489 CA LEU 1490 HA LEU 1491 CB LEU 1492 HB1 LEU 1493 HB2 LEU 1494 CG LEU 1495 HG LEU 1496 CD1 LEU 1497 HD11 LEU 1498 HD12 LEU 1499 HD13 LEU 1500 CD2 LEU 1501 HD21 LEU 1502 HD22 LEU 1503 HD23 LEU 1504 C LEU 1505 0 LEU 1506 N VAL 1507 HN VAL 1508 CA VAL 1509 HA VAL 1510 CB VAL 1511 HB VAL 1512 CG1 VAL 1513 HG11 VAL 1514 HG12 VAL 1515 HG13 VAL 1516 CG2 VAL -11.718 -12.984 -11.875 -11.463 -12.291 -12.614 -12.285 -8.604 -8.206 -8.239 -8.595 -7.304 -7.711 -7.136 -8.075 -6.896 -6.040 -6.152 -6.175 -6.047 -5.423 -7.157 -4.661 -4.747 -4.145 -4.041 -5.964 -5.212 -5.717 -6.369 -4.483 -3.708 -4.167 -5.089 -3.214 -2.368 -2.841 -3.721 -3.568 -2.126 -1.103 -2.210 -1.684 -3.485 -3.848 -4.090 0.450 0.978 0.813 0.343 1.910 2.718 2.341 2.740 1.473 3.394 4.126 4.116 3 .422 4.899 4.578 2 .743 1.657 3 .084 2 .990 1.501 2.332 0.177 -0.466 -0.294 0.431 -1.655 -2.232 -2.369 -1.727 -3.281 -2 .622 -1.529 -4.282 -4.954 -6.421 -7.448 -6.319 -5.445 -7.115 -5.387 -6.406 -4.163 -3.346 -4.075 -4.689 -2.623 -2.250 -2.008 -2.474 -3.274 -1.135 -0.304 -1.038 -1.040 -2 .592 -2.644 -3.489 -1.733 -4.681 -5.165 -4.646 -4.266 -5.190 -4.939 -4.620 -4.566 -5.557 -5.801 -5.112 -6.491 -3.223 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.35 1.33 1.40 1.73 1.91 2.33 2.19 0.94

AO.A

0.92 0.89 0.92 0.79 0.80 0.76 0.82 0.77 0.67 0.67 0.69 1.19 1.21 1.26 0.59 1.19 1.08 1.22 0.72 0.66 0.74 0.80 0.69 0.61 0.71 0.79 0.70 1.07 1.28 1.23 0.68

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

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ACSY

ACSY

ACSY

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ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

425 ATOM 1517 HG21 VAL ATOM 1518 HG22 VAL ATOM 1519 HG23 VAL ATOM 1520 ATOM 1521 ATOM 1522 ATOM 1523 ATOM 1524 ATOM 1525 1 0 ATOM 1526 ATOM 1527 ATOM 1528 ATOM 1529 ATOM 1530 1 5 ATOM 1531 ATOM 1532 ATOM 1533 ATOM 1534 ATOM 1535 ATOM 1536 ATOM 1537 ATOM 1538 ATOM 1539 ATOM 1540 ATOM 1541 ATOM 1542 ATOM 1543 ATOM 1544 ATOM 1545 ATOM 1546 ATOM 1547 ATOM 1548 ATOM 1549 ATOM 1550 ATOM 1551 ATOM 1552 ATOM 1553 ATOM 1554 ATOM 1555 C VAL O VAL N GLU HN GLU CA GLU HA GLU CB GLU HB1 GLU HB2 GLU CG GLU HGI GLU HG2 GLU CD GLU OE1 GLU OE2 GLU C GLU O GLU

SHIS

H-N HIS CA HIS "A HIS C3 HIS 31 HIS HB2 HIS CG HIS CD2 HIS -HD2 HIS NDl HIS =D1 HIS CEl HIS

HIS

NE2 HIS C HIS o HIS

TYR

-2N TYR -4.205 -3.461 -2.585 -4.591 -3.748 -5.662 -6.349 -5.812 -4.903 -7.007 -7.058 -6.872 -8.310 -8.924 122 -9.073 -9.095 -9.636 -5.953 -5.363 -6.772 -7.226 -6.985 -7.441 -7 847 -8.606 -7.242 -8 .490 -7 .948 -6.973 -9.727 -10.348 -9 .939 -10.845 879 -5.658 -5.279 -5.001 -5.406 -0.917 -2.507 -1.063 -0.413 0.061 -1.112 -1.462 -1.312 -1.797 -2.188 -2.411 -3.120 -1.553 -2.287 -0.741 -1.014 0.201 -1.816 0.022 -2.584 -2.758 -3.264 -6.691 -7.425 -7.097 -6.439 -8.522 -8.869 -8.797 -9.856 -8.279 -8.351 -7.840 -7.660 -9.563 -9.750 -10.306 -9.219 0.278 -10.261 0.851 -8.574 0.559 -7.711 2.160 -9.159 2.007 -10.125 3.019 -8.251 2.423 -7.779 3.464 -7.461 4.114 -9.066 5.366 -9.409 5.740 -9.133 4.030 -9.601 3.275 -9.530 5.187 -10.251 5.426 -10.788 6.010 -10.150 2.831 -9.357 3.238 -10.440 2.927 -8.218 2.574 -7.386 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.08 1.32 1.23 0.74 0.72 0.85 0.88 0.92 0.91 1.04 1.10 1.18 1.13 1.22 1.15 1.40 1.89 1.87 0 .92 0.94 0.91 0.91 0.91 0.99 0.90 0.93 0.82 0.95 0.95 1 .03 1.13 1.31 1.11 1.26 1.01 0.84 0.88 0.74 0.73

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

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ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

426

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1556 CA TYR 1557 HA TYR 1558 CB TYR 1559 HB1 TYR 1560 HB2 TYR 1561 CG TYR 1562 CD1 TYR 1563 HD1 TYR 1564 CE1 TYR 1565 HE1 TYR 1566 CD2 TYR 1567 HD2 TYR 1568 CE2 TYR 1569 HE2 TYR 1570 CZ TYR 1571 OH TYR 1572 HH TYR 1573 C TYR 1574 0 TYR 1575 N SER 1576 HN SER 1577 CA SER 1578 HA SER 1579 CB SER 1580 HB1 SER 1581 HB2 SER 1582 OG SER 1583 HG SER 1584 C SER 1585 0 SER 1586 N TYR 1587 HN TYR 1588 CA TYR 1589 HA TYR 1590 CB TYR 1591 HB1 TYR 1592 HB2 TYR 1593 CG TYR 1594 CD1 TYR -3.701 -3 .838 -3.164 -3.467 -2 .083 -3.669 -2.866 -1.873 -3.355 -2.736 -4.966 -5.577 -5.450 -6 .433 645 -5.118 -5.995 -2 .756 -1.780 -3.099 -3.901 -2.281 -1.260 -2 853 -3.516 -3.431 -1.838 -2.269 -2.325 -1.539 -3.308 -3.883 -3.517 -3.215 -4.985 -5.218 -5.167 -5.918 -7.280 3.552 4.557 3.628 2.753 3.636 4.873 5.559 5.200 6.724 7.255 5.373 4.880 6.533 6.915 7.206 8.340 8.529 2.782 3.320 1.489 1.067 -8.222 1.00 -8.627 1.00 -6.809 1.00 -6.240 1.00 -6.831 1.00 -6.123 1.00 -5.180 1.00 -4.955 1.00n -4.539 1.00 -3.839 1.00 -6.414 1.00 -7.148 1.00 -5.773 1.00 -6.017 1.00 -4.834 1.00 -4.205 1.00 -4.511 1.00 -9.143 1.00 -9.647 1.00 -9.339 1.00 -8.866 1.00 0.67 0.69 0.57 0.57 0.53 0.56 1.41 2.30 1.41 2.30 1.27 2.16 1.27 2.15 0.56 0.58 1.05 0.70 0.70 0.75 0.77 0.79 0.73 0.84 0.82 0.91 0.82 1.21 0 .87 0.91 0.89 0.86 0.97 1 .02 1.02 0.97 1.08 1.06 1.54

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

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ACSY

ACSY

ACSY

0.713 -10.253 0.710 -9.873 -0.680 -10.324 -0.841 -9.491 -0.811 -11.233 -1.651 -10.290 -2.496 -10.305 1.363 -11.641 1.064 -12.533 2.273 -11.737 2.467 -10.936 2.985 -12.972 2.336 -13.796 3.386 -13.072 4.130 -12.312 3.856 -14.023 2.217 -12.907 2.439 -12.595 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 427 ATOM 1595 HD1 TYR 93 -7.641 3.450 -12.459 1.00 2.26 ACSY a a a.

a. a ATOM 1596 ATOM 1597 ATOM 1598 ATOM 1599 ATOM 1600 ATOM 1601 ATOM 1602 ATOM 1603 ATOM 1604 ATOM 1605 ATOM 1606 ATOM 1607 ATOM 1608 1 5 ATOM 1609 ATOM 1610 ATOM 1611 ATOM 1612 ATOM 1613 ATOM 1614 ATOM 1615 ATOM 1616 ATOM 1617 ATOM 1618 25 ATOM 1619 ATOM 1620 ATOM 1621 ATOM 1622 ATOM 1623 ATOM 1624 ATOM 1625 ATOM 1626 ATOM 1627 ATOM 1628 ATOM 1629 ATOM 1630 ATOM 1631 ATOM 1632 ATOM 1633 CE1 TYR HE1 TYR CD2 TYR HD2 TYR CE2 TYR HE2 TYR CZ TYR OH TYR HH TYR C TYR O TYR N LYS HN LYS CA LYS HA LYS CB LYS HB1 LYS HB2 LYS CG LYS HG1 LYS HG2 LYS CD LYS HD1 LYS HD2 LYS CE LYS HE1 LYS HE2 LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS 0 LYS N ALA HN ALA CA ALA HA ALA CB ALA -8.165 -9.202 -5.449 -4.406 -6.333 -5.967 -7.691 -8.554 -8.085 -2.678 -1.841 -3.031 -3.793 -2.372 -1.506 -3.373 -2.973 -3.535 -4.696 -5.048 -4.529 -5.773 -6.461 -5.314 -6.550 -5.873 -7.077 -7.538 -8.225 -7.060 -8.033 -1.950 -2 .132 -1.379 -1.244 -0.943 -0.569 0.147 1.348 -12.436 1.524 -12.192 0.888 -13.057 0.709 -13.275 -0.204 -12.898 -1.214 -13.007 0.026 -12.588 -1.039 -12.434 -1.849 -12.582 4.242 -12.954 4.488 -13.809 5.029 -11.929 4.781 -11.361 6.279 -11.711 6.337 -12.371 7.361 -11.999 8.319 -11.689 7.415 -13.055 7.090 -11.267 6.082 -11.495 7.122 -10.188 8.102 -11.652 8.239 -10.817 9.072 -11.844 7.643 -12.887 7.465 -13.722 6.710 -12.683 8.625 -13.318 8.784 -12.554 9.520 -13.546 8.271 -14.162 6.436 -10.267 5.579 -9.415 7.619 -10.084 8.223 -10.867 8.000 -8.756 7.101 -8.261 9.064 -8.862 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.59 2.31 1.63 2.37 1.67 2.41 1.16 1.23 1.48 0.94 0.98 0.87 0.86 0.85 0.88 0.88 0.86 0.96 0.87 0.90 0.79 0.93 0.97 0.94 1.00 1.06 1.13 1.05 1.22 1.48 1.28 0.74 0.69 0.73 0.79 0.65 0.61 0.68

ACSY

ACSY

ACSY

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ACSY

ACSY

428 ATOM 1634 ATOM 1635 ATOM 1636 ATOM 1637 ATOM 1638 ATOM 1639 ATOM 1640 ATOM 1641 ATOM 1642 ATOM 1643 ATOM 1644 ATOM 1645 ATOM 1646 ATOM 1647 1 5 ATOM 1648 ATOM 1649 ATOM 1650 ATOM 1651 ATOM 1652 ATOM 1653 ATOM 1654 ATOM 1655 ATOM 1656 ATOM 1657 ATOM 1658 ATOM 1659 ATOM 1660 ATOM 1661 ATOM 1662 ATOM 1663 ATOM 1664 ATOM 1665 ATOM 1666 ATOM 1667 HB1 ALA HB2 ALA HB3 ALA C ALA O ALA N ASP HN ASP CA ASP HA ASP CB ASP HB1 ASP HB2 ASP CG ASP OD1 ASP OD2 ASP C ASP O ASP N GLY HN GLY CA GLY HA1 GLY HA2 GLY C GLY 0 GLY N LEU HN LEU CA LEU HA LEU CB LEU HB1 LEU HB2 LEU CG LEU HG LEU CD1 LEU -0.193 0.424 1.043 -2-.152 -2.392 -2.903 652 -4.090 -4.639 -4.918 -4.416 -5.050 -6.294 -6.887 -6.758 -3.708 -4.534 -2.410 826 -1.873 -2.565 -1.836 -0.472 0.337 -0.238 -0.934 1.055 1 .112 1 .219 1 .340 2.129 0.038 -0.873 0.100 -0.738 1.022 0.058 0.026 0.770 9.911 9.437 8.659 8.539 8.199 9.392 9.617 9.981 10.467 8.885 7.926 9.086 8.806 7.729 9.822 11.031 11.780 11.019 10.370 11.951 11.987 12.931 11.532 12.354 10.205 9.581 9 .704 9 .776 8.265 8 .252 7 .848 7.395 7.896 6.066 5.965 5.980 5.239 7.185 6.455 -9.458 -7.876 -9.333 -7.986 -6.836 -8.711 -9.653 -8.094 -8.876 -7.457 -7.558 -6.398 -8.125 -8.119 -8.640 -7.049 -6.541 -6.779 -7.253 -5.807 -4.966 -6.279 -5.339 -4.926 -5.433 -5.788 -5.021 -3.925 -5.497 -6.580 -5.078 -5.110 -5.408 -5.843 -6.534 -6.417 -5.139 -3.598 -3.298 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.18 1.19 1.17 0.63 0.57 0.70 0.75 0.70 0.77 0.69 0.79 0.74 0.79 1.31 1.32 0.66 0.69 0.63 0.62 0.61 0.73 0.75 0.56 0.58 0.53 0.54 0 .50 0 .46 0.48 0.55 0.47 0.43 0 .47 0 .47 1 .15 1.15 1.03 0.35 1.06

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ATOM

ATOM

ATOM

ATOM

ATOM

1668 HD11 LEU 1669 HD12 LEU 1670 HD13 LEU 1671 CD2 LEU 1672 HD21 LEU 429 ATOM 1673 HD22 LEU 0.246 8.116 -3.082 1.00 0.99 ACSY

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1674 HD23 LEU 1675 C LEU 1676 0 LEU 1677 N LEU 1678 HN LEU 1679 CA LEU 1680 HA LEw 1681 CB LEU 1682 HB1 LEU 1683 HB2 LEU 1684 CG LEU 1685 HG LEU 1686 CD1 LEU 1687 HD11 LEU 1688 HD12 LEU 1689 HD13 LEU 1690 CD2 LEU 1691 HD21 LEU 1692 HD22 LEU 1693 HD23 LEU 1694 C LEU 1695 0 LEU 1696 N ARG 1697 HN ARG 1698 CA ARG 1699 HA ARG 1700 CB ARG 1701 HB1 ARG 1702 HB2 ARG 1703 CG ARG 1704 HG1 ARG 1705 HG2 ARG 1706 CD ARG 1707 HDI ARG 1708 HD2 ARG 1709 NE ARG 1710 HE ARG 1711 CZ ARG 98 98 98 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99 99 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 100 2.138 1.872 3.375 3.522 4.492

A

332 5.792 5.589 6.186 6.841 7.754 7.160 7.519 6.274 7.930 6.357 7.159 5.529 6.017 4.478 4.691 4.202 4.074 4.120 3 .668 5.516 6 .226 5.815 5.575 6 .477 4.731 5.560 6.372 4.617 5.724 5.797 5.779 10.548 -5.672 11.478 -6.424 10.155 -5.342 9.409 -4.691 10.841 -5.957 11.912 -5.828 10.386 -5.303 10.060 -4.285 9.521 -5.839 11.497 -5.281 11.098 -4.836 11.959 -6.700 11.128 -7.306 12.371 -7.182 12.730 -6.693 12.675 -4.431 13.397 -4.277 13.191 -4.916 12.335 -3.453 10.492 -7.450 11.328 -8.319 9.187 -7.665 8.568 -6.894 8.684 -9.017 9.464 -9.635 8.332 -9.501 9.084 -9.154 7.387 -9.055 8.227 -11.026 7.692 -11.320 7.639 -11.386 9.606 -11.684 10.236 -11.317 10.123 -11.517 9.481 -13.121 8.581 -13.550 10.602 -13.865 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0.59 0.68 0.64 0.64 0.74 0.78 0.79 0.75 0.82 0.94 1.38 1.40 2.02 1.75 1.88 1.40 1.86 1.85 1.98 0.78 0.87 0.73 0.68 0.78 0.82 0.85 0.88 0.83 0.95 1.53 1.34 1.59 2 .22 2 .14 2.14 2.41 2.96 -0.948 6.840 -3.260 1.00 0.89 ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

430 ATOM 1712 NH1 ARG 100 5.932 10.517 -15.184 1.00 3.73 ACSY

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1 5 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1714 1715 1716 1717 1718 1719 1720 1721 1722 1723 1724 1725 1726 1727 1728 1729 1730 1731 1732 1733 1734 '735 1736 :737 -738 1739 1740 :741 HH12 NH2 HH21 HH22

C

0

N

HN

ARG

ARG

ARG

ARG

ARG

ARG

VAL

VAL

1713 HH11 ARG CA VAL 101 HA VAL 101 CB VAL 101 HB VAL 101 CG1 VAL 101 HG11 VAL 101 HG12 VAL 101 HG13 VAL 101 CG2 VAL 101 HG21 VAL 101 HG22 VAL 101 HG23 VAL 101 C VAL 101 0 VAL 101 N LEU 102 HN LEU 102 CA LEU 102 HA LEU 102 CB LEU 102 HB1 LEU 102 HB2 LEU 102 CG LEU 102 HG LEU 102 CD1 LEU 102 HDIl LEU 102 HD12 LEU 102 HD13 LEU 102 CD2 LEU 102 HD21 LEU 102 100 100 100 100 100 100 100 101 101 6.007 5.973 5.680 5.565 5 .721 3 .227 3 .057 2 .672 2 .847 1.813 0 .882 1.532 2.404 0.361 0.680 -0.384 -0.100 1.267 0.415 2.133 1.050 2.523 3 .678 1.736 0.790 2 .261 3 .189 1 .230 0.273 1.490 1.116 1.965 1.140 0.303 1 .073 2 .064 -0.166 -0.238 9.621 -15.622 11.349 -15.737 11.794 -13.283 11.859 -12.292 12.626 -13.837 7.440 -9.018 6.769 -8.008 7.184 -10.213 7.767 -10.997 6.038 -10.359 6.226 -9.800 5.858 -11.835 5.399 -12.291 4.930 -12.035 3.892 -12.001 5.078 -11.262 5.115 -12.995 7.205 -12.512 7.709 -12.054 7.861 -12.424 7.073 -13.572 4.786 -9.844 4.806 -9.439 3.704 -9.902 3.793 -10.196 2.409 -9.513 2.552 -8.950 1.647 -8.706 1.720 -9.199 0.595 -8.697 2.153 -7.271 1.780 -6.707 3.675 -7.208 4.106 -7.759 4.007 -6.177 4.070 -7.622 1.625 -6.634 1.930 -5.591 1.00 1.00 1.00 1.00 1.00 1.00 1 f .J uu 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.oo 3.85 4.41 3.46 3.29 4.28 0.73 0.66 0.78 0.84 0.76 0.71 0.85 0.90 0.85 1.38 1.24 1.32 0.90 1.41 1.26 1.35 0.72 0.72 0.71 0 .73 0.70 0 .67 0.66 0 .71 0.69 0.58 0.59 0.59 1.18 1.10 1.22 0.58 1.16

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

1742 1743 1744 -745 1746 1747 1748 1749 1750 431 ATOM 1751 HD22 LEU 102 -1.043 2.004 -7.158 1.00 1.23

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1752 HD23 LEU 1753 C LEU 1754 0 LEU 1755 N THR 1756 HN THR 1757 CA THR 1758 HA THR 1759 CB THR 1760 HB THR 1761 OG1 THR 1762 HG1 THR 1763 CG2 THR 1764 HG21 THR 1765 HG22 THR 1766 HG23 THR 1767 C THR 1768 0 THR 1769 N VAL 1770 HN VAL 1771 CA VAL 1772 HA VAL 1773 CB VAL 1774 HB VAL 1775 CG1 VAL 1776 HG11 VAL 1777 HG12 VAL 1778 HG13 VAL 1779 CG2 VAL 1780 HG21 VAL 1781 HG22 VAL 1782 HG23 VAL 1783 C VAL 1784 0 VAL 1785 N PRO 1786 CD PRO 1787 HD1 PRO 1788 HD2 PRO 1789 CA PRO 102 102 102 103 103 103 103 103 103 103 103 103 103 103 103 103 103 104 104 104 104 104 104 104 104 104 104 104 104 104 104 104 104 105 105 105 105 105 -0.199 2.569 2.100 3.388 3.745 3.775 2.939 5.010 5.287 4.698 5.148 6.201 5.989 7.081 6.438 4.071 3.769 4.679 4.859 5.068 4.447 6.549 7.089 7.086 6.698 8.174 6.807 6.803 5.895 7.559 7.156 4.929 5.117 4.584 4.141 4.956 3.323 4.526 0.539 -6.673 1.641 -10.778 1.957 -11.864 0.619 -10.562 0.435 -9.651 -0.181 -11.694 -0.178 -12.397 0.480 -12.307 1.338 -11.699 0.962 -13.589 1.791 -13.686 -0.464 -12.388 -1.298 -13.052 0.055 -12.763 -0.862 -11.402 -1.619 -11.267 -2.575 -11.971 -1.704 -10.072 -0.870 -9.533 -3.036 -9.598 -3.772 -10.109 -3.223 -9.928 -2.402 -9.443 -4.541 -9.368 -5.390 -9.929 -4.572 -9.429 -4.667 -8.325 -3.172 -11.436 -2.926 -11.978 -2.427 -11.681 -4.137 -11.800 -3.187 -8.087 -2.248 -7.333 -4.441 -7.680 -5.492 -8.580 -5.801 -9.229 -5.131 -9.202 -4.805 -6.277 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1 .00 1.00 1.00 1.00 1.00 1 .00 1.00 1.00 1 .00 1 .00 1.00 1.00 1.00 1.14 0.81 0.87 0.83 0.79 0.94 0.98 1.01 0.96 1.08 1.35 1.18 1.35 1.83 1.58 0.96 1.04 0.88 0.82 0.90 0.98 0.96 0.92 1 .04 1.68 1.20 1.35 1.10 1.53 1.38 1.64 0.76 0.65 0.79 0.94 1.00 1.01 0.70

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

432 ATOM 1790 HA PRO 105 3.974 -4.055 -5.720 1.00 0.64 C

C

C

S

C

C. C

C

C

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

3 5 ATOM

ATOM

ATOM

ATOM

ATOM

1791 1792 1793 1794 1795 1796 1797 1798 1799 1800 1801 1802 1803 1804 1805 1806 1807 1808 1809 1810 1811 1812 1813 1814 1815 1816 1817 1818 1819 1820 1821 1822 CB PRO HB1 PRO HB2 PRO CG PRO HG1 PRO HG2 PRO C PRO O PRO N CYS HN CYS CA CYS HA CYS CB CYS HB1 CYS HB2 CYS SG CYS HG CYS C CYS O CYS N GLN HN GLN CA GLN HA GLN CB GLN HB1 GLN HB2 GLN CG GLN HG1 GLN HG2 GLN CD GLN OE1 GLN NE2 GLN 105 105 105 105 105 105 105 105 106 106 106 106 106 106 106 106 106 106 106 107 107 107 107 107 107 107 107 107 107 107 107 107 107 107 107 107 108 108 3.848 4.435 2.887 3.684 4.286 2.644 5.959 5 .7 6.827 6.152 5.383 7.509 8.176 7.712 7.750 6.872 9.228 8.949 7.846 8.734 7 .109 6.392 7.354 8 .163 6 .118 5.433 5.627 6.448 7.149 5.555 7.062 6.721 7.988 8.215 8.463 7.794 7.599 8.369 8.418 -6.170 -6.878 -6.081 -6.645 -7.535 -6.902 A -4.892 -5.503 -4.263 -3.882 -4.211 -4.252 -2.909 -2.086 -2.721 -2.923 -2.555 -5.370 -6.167 -5.378 -4.706 -6.380 -6.001 -6.573 -5.770 -7.483 -6.608 -5.810 -6.456 -7.954 -8.999 -7.852 -6.962 -8.663 -7.697 -8.015 -8.437 -8.089 -6.222 -5.639 -5.741 -7.676 -7.858 -7.880 -5.745 -6.355 -4.585 -4.072 -4.069 -4.931 -3.322 -4.022 -2.665 -2.337 -1.085 -3.154 -3.429 -2.035 -1.893 -1.035 -0.405 -0.207 -0.402 -0.508 1.278 1.520 1.869 1 .664 1 .125 2 .634 3 .030 2 .974 -1.634 -2.801 -0.701 0.238 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 0.82 0.81 0.86 0.97 1.02 1.06 0.65 0.71 0.58 0.57 0.61 0.64 0.74 1.16 0.97 1.05 1.70 0.66 0.80 0.66 0.68 0 .77 0.87 0.88 0.88 0.93 1.08 1.10 1.31 1.41 2.03 1.85 2.21 2.23 0.83 0.90 0.89 0.91

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

1823 HE21 GLN 1824 HE22 GLN 1825 C GLN 1826 0 GLN 1827 N LYS 1828 HN LYS 433 a a a.

a a

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

15 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

25 ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

ATOM

1829 1830 1831 1832 1833 1834 1835 1836 1837 1838 1839 1840 1841 1842 1843 1844 1845 1846 1847 1848 1849 1850 1851 1852 1853 1854 1855 1856 1857 1858 1859 1860 1861 1862 1863 1864 1865 1866 1867 CA LYS HA LYS CB LYS HB1 LYS HB2 LYS CG LYS HG1 LYS HG2 LYS CD LYS HD1 LYS HD2 LYS CE LYS HE1 LYS HE2 LYS NZ LYS HZ1 LYS HZ2 LYS HZ3 LYS C LYS 0

N

HN

CA

HA

CB

HB

CG2 HG21 HG22 HG2 3 CG1

HGII

HGI2 CD1 HDI 1 HD12 HD13

C

0

LYS

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

ILE

108 108 108 108 108 108 108 108 108 108 108 108 108 108 108 108 108 108 108 108 109 109 109 109 109 109 109 109 109 109 109 109 109 109 109 109 109 109 109 8.908 -9.729 9.706 -9.569 9.468 -10.322 8.818 -10.086 9.512 -11.409 10.850 -9.764 11.522 -10.228 10.853 -8.697 11.331 -9.989 12.248 -9.422 10.590 -9.596 11.581 -11.470 11.877 -11.611 10.675 -12.052 12.633 -12.031 12.315 -12.047 13.489 -11.446 12.845 -13.000 7.874 -10.654 6.720 -10.310 8.401 -11.863 9.363 -12.046 7.566 -12.890 6.748 -12.385 8.394 -13.727 9.120 -14.307 7.495 -14.698 6.458 -14.363 7.535 -15.697 7.807 -14.772 -1.026 -1.756 0.245 1.087 0.166 0.480 -0.226 0.259 1.909 2.074 2.606 2.199 3.238 2.030 1.359 0.369 1.439 1.672 -1.631 -1.854 -1.875 -1.647 -2.464 -2.982 -3.439 -2.865 -4.206 -4.189 -3.774 -5.248 -4.423 -5.221 -4.874 -3.768 -2.927 -4.482 -3.399 -1.358 -0.445 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1 .00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.10 0.99 1.06 1.62 1.43 2.09 1.80 1.58 1.75 1.59 1.99 2.24 2.32 2 .54 2.99 2.75 2.98 1.21 1.28 1.48 1.55 1.78 1.89 2.08 2.22 2.57 2.80 2.99 3.08 2.79 3 .11 3.35 3.27 3.76 3 .43 3.61 1.95 2.27

ACSY

ACSY

ACSY

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ACSY

ACSY

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ACSY

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ACSY

ACSY

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9.151 9.511 8.476 10.333 10.720 11.144 10.038 6.992 6.314 -12.856 -13.493 -12.128 -12.138 -12.713 -11.997 -11.156 -13.779 -13.325 434

S

oe

C

*S*

S

*SSS

S

15 25 ATOM 1868 ATOM 1869 ATOM 1870 ATOM 1871 ATOM 1872 ATOM 1873 ATOM 1874 ATOM 1875 ATOM 1876 ATOM 1877 ATOM 1878 ATOM 1879 ATOM 1880 ATOM 1881 ATOM 1882 ATOM 1883 ATOM 1884 ATOM 1885 ATOM 1886 ATOM 1887 ATOM 1888 ATOM 1889 ATOM 1890 ATOM 1891 ATOM 1892 ATOM 1893 ATOM 1894 ATOM 1895 ATOM 1896 ATOM 1897 ATOM 1898 ATOM 1899 ATOM 1900 ATOM 1901 ATOM 1902 ATOM 1903 ATOM 1904 ATOM 1905 ATOM 1906

C

0

N

HN

CA

HA

CB

HB

OG1 HG1 CG2 HG21 HG2 2 HG2 3

C

0

N

HN

HA

CB

HB1 HB2

CG

HG1 HG2

CD

OE1 NE2 HE21 HE2 2

C

OCT1 OCT2

CA

GLY

GLY

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

THR

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

GLN

N GLY HN GLY CA GLY HA1 GLY HA2 GLY 110 110 110 110 110 110 110 111 111 111 111 111 111 111 111 111 111 111 111 111 111 112 112 112 112 112 112 112 112 112 112 112 112 112 112 112 112 112 112 7.318 -15.075 7.881 -15.361 6.846 -16.042 6.075 6.405 7.992 8.812 7.988 7.275 9.006 9.294 8.406 8.823 7.016 6.733 8.659 9.727 8.229 8.213 10.223 11.188 10.106 9.300 12.023 11.526 10.613 12.131 12.273 11.671 13.206 12.590 12.590 12.859 12.840 13.081 10.750 10.566 10.606 11.179 -16.645 -15.489 -16.927 -16.529 -18.152 -18.429 -19.093 -18.873 -20.497 -21.017 -20.413 -19.585 -21.301 -21.403 -22.295 -20.810 -18.920 -18.242 -19.575 -20.129 -19.036 -20.900 -21.428 -20.835 -21.693 -21.777 -21.195 -23.098 -23.363 -23.973 -23.684 -24.925 -18.616 -19.149 -17.410 -19.495 -1.515 -2.302 -0.543 -1.024 0.286 -0.050 0.768 -0.608 -1.240 -0.237 0.792 -0.351 -1.202 -0.568 -0.204 0.902 1.081 0.812 1.765 -1.152 -0.821 -2.315 -2.502 -2.761 -3.757 -4.033 -4.654 -2.685 -1.780 -2.418 -3.202 -4.398 -2.216 -1.259 -2.425 -4.449 -5.543 -4.259 -3.273 1.00 2.16 1.00 2.31 1.00 2.55 1.00 2.98 1.00 2.78 1.00 2.95 1.00 3.24 1.00 3.69 1.00 3.93 1.00 4.59 1.00 4.56 1.00 5.48 1.00 5.47 1.00 6.29 1.00 6.55 1.00 6.06 1.00 6.29 1.00 6.36 1.00 6.33 1.00 5.25 1.00 5.77 1.00 5.59 1.00 5.45 1.00 6.65 1.00 7.76 1.00 7.73 1.00 8.48 1.00 8.32 1.00 8.37 1.00 8.00 1.00 9.59 1.00 10.22 1.00 10.08 1.00 9.69 1.00 10.94 1.00 6.55 1.00 6.59 1.00 6.79 1.00 6.56

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

ACSY

435

END

*Note: See copyright notice on page 1.

*000 436 SEQUENCE LISTING GENERAL INFORMATION: APPLICANT: ARIAD PHARMACEUTICALS, INC.

(ii) TITLE OF INVENTION: CRYSTALLINE ZAP-FAMILY PROTEINS (iii) NUMBER OF SEQUENCES: (iv) CORRESPONDENCE ADDRESS: ADDRESSEE: David L. Berstein, ARIAD Pharmaceuticals, Inc.

STREET: 26 Landsdowne Street 15 CITY: Cambridge STATE: Massachusetts COUNTRY: USA ZIP: 02139-4234 20 COMPUTER READABLE FORM: MEDIUM TYPE: Floppy disk COMPUTER: IBM PC compatible OPERATING SYSTEM: PC-DOS/MS-DOS SOFTWARE: PatentIn Release Version #1.30 (vi) CURRENT APPLICATION DATA: APPLICATION NUMBER: PCT/US96/13918 FILING DATE: 30-AUG-1996

CLASSIFICATION:

(vii) PRIOR APPLICATION DATA: APPLICATION NUMBER: US 60/002,972 FILING DATE: 30-AUG-1995 (vii) PRIOR APPLICATION DATA: APPLICATION NUMBER: US 60/003,312 FILING DATE: 06-SEP-1995 (viii) ATTORNEY/AGENT INFORMATION: 437 NAME: BERSTEIN, David L.

REGISTRATION NUMBER: 31,235 REFERENCE/DOCKET NUMBER: 347C-PCT (ix) TELECOMMUNICATION INFORMATION: TELEPHONE: 617-494-0400 TELEFAX: 617-494-0208 INFORMATION FOR SEQ ID NO:1: SEQUENCE CHARACTERISTICS: LENGTH: 15 amino acids TYPE: amino acid STRANDEDNESS: single 15 TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:1: Tyr Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Tyr Xaa Xaa Leu 1 5 10 INFORMATION FOR SEQ ID NO:2: SEQUENCE CHARACTERISTICS: 0: LENGTH: 19 amino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= "Acetylated" /label= Ac 438 (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 4 OTHER INFORMATION: /product= "phosphotyrosine' /label= pTyr /note= "phosphorylated tyrosine" (ix) FE.A.UE NAME/KEY: Modified-site 1 0 LOCATION: OTHER INFORMATION: /product= "phosphotyrosine' /label= pTyr /note= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 19 OTHER INFORMATION: /product= "axidated" /labei= NH2 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: Asp Gly Val Tyr Thr Gly Leu Ser Thr Arg Asn Gin Giu Thr Tyr 1 5 10 Clii Thr Leu Lys INFORMATION FOR SEQ ID NO:3: Ci) SEQUENCE CHARACTERISTICS: CA) LENGTH: 15 amino acids TYPE: amino acid STRANDEDNESS: single CD) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: 439 WO 97/08300 NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= "Acetylated" /label= Ac (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= "phosphotyrosine" 1 0 /label= pTyr /note= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 12 OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr /note= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: OTHER INFORMATION: /product= "aridated" /label= NH2 (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 3: Tyr Thr Gly Leu Ser Thr Arg Asn Gin Glu Thr Tyr Glu Thr Leu 1 5 10 INFORMATION FOR SEQ ID NO:4: SEQUENCE CHARACTERISTICS: LENGTH: 25 amino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide 440 (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= "Acetylated" /label= Ac (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 4 OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr /note= "phosphorylated" 15 (ix) FEATURE: NAME/KEY: Modified-site LOCATION: OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr /note= "phosphorylated tyrosine" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: Asp Gly Val Tyr Thr Gly Leu Ser Thr Arg Asn Gin Glu Thr Tyr Glu 1 5 10 Thr Leu Lys His Glu Lys Pro Pro Gin INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 27 amino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide 441 (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= "Acetylated" /label= Ac (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 6 OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr /note= 'phosphorylated tyrosine" (ix) FEATURE: 1 5 NAME/KEY: Modified-site LOCATION: 17 OTHER INFORMATION: /product= "phosphotyrosine" */label= pTyr /note= "phosphorylated tyrosine" (xi) SEQUENCE DESCRIPTION: SEQ ID *Lys Ser Asp Gly Val Tyr Thr Gly Leu Ser Thr Arg Asn Gin Glu Thr 1 5 10 Tyr Glu Thr Leu Lys His Glu Lys Pro Pro Gin INFORMATION FOR SEQ ID. NO:6: SEQUENCE CHARACTERISTICS: LENGTH: 19 amino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: 442 NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= "Acetylated" /label= Ac (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 4 OTHER INFORMATION: /product= "phosphotyrosine" 1 0 /label= pTyr /note= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr /note= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 19 OTHER INFORMATION: /product= "Amidated" /label= NH2 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: Asn Gin Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp 1 5 10 Val Leu Asp INFORMATION FOR SEQ ID NO:7: SEQUENCE CHARACTERISTICS: LENGTH: 19 amino acids TYPE: amino acid STRANDEDNESS: single 443 TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= "Acetylated" /label= Ac 1 0 (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 3 OTHER INFORMATION: /product= "phosphotyrosine" 1 5 /label= pTyr /nlote= "phosphorylated" (ix) FEATURE: NAME/KEY: Modified-site 20 LOCATION: 11 OTHER INFORMATION: /product= "Norleucine" /label= Nie (ix) FEATURE: NAME/KEY: Modified-site LOCATION: OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr /note= "phosphorylated" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 19 OTHER INFORMATION: /product= "Amidated" /label= NH2 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: 444 Gly Leu Tyr Asn Glu Leu Gin Lys Asp Lys Xaa Ala Glu Ala Tyr Ser 1 5 10 Glu Ile Gly INFORMATION FOR SEQ ID NO:8: SEQUENCE CHARACTERISTICS: 1 0 LENGTH: 19 amino acids TYPE: amino acid STRANflEDNESS: single TOPOLOGY: linear 1 5 (ii) MOLECULE TYPE: peptide (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= 'Acetylated" /label= Ac (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 4 OTHER INFORMATION: /product= 'phosphotvrosine" /label= pTyr /note= 'phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr /note= 'phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 19 445 OTHER INFORMATION: /product= 'Amidated" /label= NH2 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: Asp Gly Leu Tyr Gin Gly Leu Ser Thr Ala Thr Lys Asp Thr Tyr Asp 1 5 10 Ala Leu His INFORMATION FOR SEQ ID NO:9: SEQUENCE CHARACTERISTICS: LENGTH: 16 amino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= "Acetylated" /label= Ac (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr /note= "lphosphorylated tyrosine" (ix) FEATURE: 3 5 NAME/KEY: Modified-site LOCATION: 3 OTHER INFORMATION: /product= p-Iodo-L- Phenylalanine" /label= pI-Phe 446 (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 12 OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr /note= "phosphorylated tyrosine" (ix) FEATURE: 1 0 NAME/KEY: Modified-site LOCATION: 16 OTHER INFORMATION: /product= "Ainidated" /label= NH2 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: Asn Gin Xaa Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp 10 20 Val Leu Asp 0 SEQUENCE CHARACTERISTICS: 0 LENGTH: 19 amino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product:= "Acetylated" /label= Ac (ix) FEATURE: 447 0 0 S.

NAME/KEY: Modified-site LOCATION: 4 OTHER INFORMATION: /product= "difluorophosphono methyl phenylalanine" /label= F2Pmp (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 0 OTHER INFORMATION: /product= "difluoropriosphono methyl phenylalanine" /label= F2Pmp (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 19 OTHER INFORMATION: /product= "Amidated' /label= NH2 o (xi) SEQUENCE DESCRIPTION: SEQ ID NO:lO: Asn Gin Leu. Phe Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Phe Asp 1 5 10 Val Leu Asp INFORMATION FOR SEQ ID NO:11: 0 Ci) SEQUENCE CHAACTERISTICS: LENGTH: 16 amiino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: NAME/KEY: Modified-site 448 LOCATION: 1 OTHER INFORMATION: /product= "Acetylated" /label= Ac (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 4 OTHER INFORMATION: /product= "nphosphotyrosine" /label= pTyr 1 0 /note= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 12 OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr /note= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 16 OTHER INFORMATION: /product= "Amidated' /label= NH2 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:l11: Asp Gly Val Tyr Thr Gly Leu Ala Ala Ala Ala Tyr Glu Thr Leu Lys 1 5 10 INFORMATION FOR SEQ ID NO:12: SEQUENCE CHARACTERISTICS: LENGTH:, 4 amino acids TYPE: amino acid STRANDEDNhSS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide 449 (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr.

/note= "phosph-irylated tyrosine" (xi) SEQUENCE DESCRIPTION: SEQ ID N0:12: Tyr Xaa Xaa Leu 1 INFORMATION FOR SEQ ID NO:13: 15 Ci) SEQUENCE CHARACTERISTICS: LENGTH: 4 amino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= 'Acetylated" /label= Ac (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr /note= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 3 OTHER INFORMATION: /product= "N-methyl glycine" -450 /label= nmGly (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 4 OTHER INFORMATION: /product= "N-methyl leucine" /label= nmLeu (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 4 OTHER INFORMATION: /product= "Amidated" /label= NH2 e (xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: Tyr Thr Gly Leu INFORMATION FOR SEQ ID NO:14: SEQUENCE CHARACTERISTICS: LENGTH: 19 amino acids TYPE: amino acid STRANDEDNESS: single S* TOPOLOGY: linear 9 6 (ii) MOLECULE TYPE: peptide (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 4 OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr /note= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 451 0000 0@ *0 0

S

0S@0 00 S S 0009 00 0 0 9000 00 0 0 OSO 0 0000 0 0000 0000 9 00..

0000 00 #9 9 0000 0 0900

S

000090 0 0 GOOSe.

0 OTHER INFORMATION: /product= "phosphotyrosine" /label= pTyr /note= "Phosphorylated tyrosine" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: Asn Gin Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp 1 5 10 1 0 Val Leu Asp INFORMATION FOR SEQ ID 15 SEQUENCE CHARACTERISTICS: LENGTH: 19 amino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 4 OTHER INFORMATION: /product= 'phosphotyrosine" /label= TyrPO4 /note= phosphorylated tyrosinie" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: OTHER INFORMATION: /product= "phosphotyrosine" /label= -TyrPO4 /note= "phosphorylated tyrosine" (xi) SEQUENCE DESCRIPTION: SEQ ID NO: Asn G-in Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr Asp 452 1 5 10 Val Leu Asp INFORMATION FOR SEQ ID NO:16: SEQUENCE CHARACTERISTICS: LENGTH: 22 amino acids 1 0 TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide 1 (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= 'Acetylated" /label= Ac (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 7 OTHER INFORMATION: /product= "phosphotyrosine' */label= TyrPO4 */nlote= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 12 OTHER INFORMATION: /product= "phosphotyrosine' /label= TyrPO4 /note= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 22 OTHER INFORMATION: /product= 'Axidated" 453 WO 97/08300 /label= NH2 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: Lys Gly Gly Asn Gin Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu 1 5 10 Glu Tyr Asp Val Leu Asp INFORMATION FOR SEQ ID NO:17: SEQUENCE CHARACTERISTICS: LENGTH: 19 amino acids 15 TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: NAME/KEY: Modified-site LOC.ATION: OTHER INFORMATION: /product= "phosphotyrosine" /label= TyrPO4 /note= "phosphorviated tyrosine" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: Asn Gin Leu Tvr Asn Giu Leu Asn Leu Gly Arg Arg Giu Giu Tyr Asp 1 5 10 Val Leu Asp INFORMATION FOR SEQ ID NO:18: SEQUENCE CHARACTERISTICS: LENGTH: 22 amino acids -454 TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 OTHER INFORMATION: /product= "Acetylated" /label= Ac (ix) FEATURE: oo.. NAME/KEY: Modified-site 15 LOCATION: 18 OTHER INFORMATION: /product= "phosphotyrosine" /label= TyrPO4 /note= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 22 OTHER INFORMATION: /product= "Amidated" /label= NH2 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: Lys Gly Gly Asn Gin Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu 1 5 10 Glu Tyr Asp Val Leu Asp INFORMATION FOR SEQ ID NO:19: SEQUENCE CHARACTERISTICS: LENGTH: 19 amino acids TYPE: amino acid STRANDEDNESS: single 455 /n TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 4 OTHER INFORMATION: /product= "phosphotyrosine' abel= TyrPO4 ote= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: OTHER INFORMATION: /product= "phosphotyrosine" abel= TyrPO4 te= 'phosphorylated tyrosine" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: Asp Gly Val Tyr Thr Gly Leu Ser Thr Arg Asn Gin Glu Thr Tyr Glu 1 5 10 /1 n Thr Leu Lys INFORMATION FOR SEQ ID SEQUENCE CHARACTERISTICS: LENGTH: 22 amino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 1 456 OTHER INFORMATION: /product= 'Acetylated" /label= Ac (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 7 OTHER INFORMA~TION: /product= "phosphotyrosine" /label= TyrPO4 /note= "phosphorylated tyrosine' (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 18 OTHER INFORMATION: /product= 'phosphotyrosine" 1 5 /label= TyrPO4 /note= "phosphorylated tyrosine" (ix) FEATURE: NAME/KEY: Modified-site LOCATION: 22 OTHER INFORMATION: /product= 'Amidated" /label= NH2 (xi) SEQUENCE DESCRIPTION: SEQ ID Cys Gly Gly Asp Gly Val Tyr Thr Gly Leu Ser Thr Arg Asn Gin Glu *1 5 10 Thr Tyr Glu Thr Leu Lys INFORMATION FOR SEQ ID NO:21: SEQUENCE CHARACTERISTICS: LENGTH: 98 amino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear 457 (ii) (v) (xi) MOLECULE TYPE: protein FRAGMENT TYPE: internal SEQUENCE DESCRIPTION: SEQ ID NO:2i: Trp Tyr Phe 1 Asn Pro Giu Thr Lys Gly 35 Gly Leu Asn Giy Asn Ala Ile Thr Arg Arg Giy Thr Arg Giu 10 Phe Leu Ser Glu Arg Leu Leu Leu Val Arg Glu 25 Val1 Tyr Cys Leu a a a a Ser 40 Lys Ser Asp Phe Asp Asp Ser Glu Thr Asn Ala Lys Ser Gly Gly Val Lys His Ilie Arg Lys Phe Tyr Ile Thr Ser Ala Arg 70 Gin Phe Asn Ser Cys Gin Gin Leu Tyr Tyr Ser Lys 85 His Ala Asp Gly His Arg Leu Thr Vai Cys INFORMATION FOR SEQ ID NO:22: SEQUENCE CHARACTERISTICS: LENGTH: 98 amino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: iinear (ii) MOLECULE TYPE: protein FRAGMENT TYPE: internal 458 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: Trp Phe Phe Lys Asn Leu Ser Arg Lys Asp Ala Glu Arg Gin Leu Leu 1 5 10 Ala Pro Gly Asn Thr His Gly Ser Phe Leu Ile Arg Glu Ser Glu Ser 25 Thr Ala Gly Ser Phe Ser Leu Ser Val Arg Asp Phe Asp Gin Asn Gin 35 40 Gly Glu Val Val Lys His Tyr Lys Ile Arg Asn Leu Asp Asn Gly Gly 55 1 5 Phe Tyr Ile Ser Pro Arg Ile Thr Phe Pro Gly Leu His Glu Leu Val 65 70 75 Arg His Tyr Thr Asn Ala Ser Asp Gly Leu Cys Thr Arg Leu Ser Arg 90 Pro Cys INFORMATION FOR SEQ ID NO:23: SEQUENCE CHARACTERISTICS: LENGTH: 97 amino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: protein FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: Trp Phe His Pro Asn Ile Thr Gly Val Glu Ala Glu Asn Leu Leu Leu 1 5 10 459 Thr Arg Gly Val Asp Gly Ser Phe Leu Ala Arg Pro Ser Lys Ser Asn 25 Pro Gly Asp Phe Thr Leu Ser Val Arg Arg Asn Gly Ala Val Thr His 40 Ile Lys Ile Gin Asn Thr Gly Asp Tyr Tyr Asp Leu Tyr Gly Gly Glu 55 Lys Phe Ala Thr Leu Ala Glu Leu Val Gin Tyr Tyr Met Glu His His 70 75 Gly Gin Leu Lys Glu Lys Asn Gly Asp Val Ile Glu Leu Lys Tyr Pro 85 90 *Leu o

L

INFORMATION FOR SEQ ID NO:24: SEQUENCE CHARACTERISTICS: LENGTH: 93 amino acids TYPE: amino acid STRANDEDNESS: single TOPOLOGY: linear (ii) MOLECULE TYPE: protein FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: Phe Phe Tyr Gly Ser Ile Ser Arg Ala Glu Ala Glu Glu His Leu Lys 1 5 10 Leu Ala Gly Met Ala Asp Gly Leu Phe Leu Leu Arg Gin Cys Leu Arg 25 460 Ser Leu Gly Gly Tyr Val Leu Ser Leu Val His Asp Val Arg Phe Hius 40 His Phe Pro Ile Glu Arg Gin Leu Asn Gly Thr Tyr Ala Ile Ala Gly 50 55 Gly Lys Ala His Cys Gly Pro Ala Glu Leu Cys Glu Phe Tyr Ser Arg 70 7 5 1 0 Asp Pro Asp Gly Leu Pro Cys Asn Leu Arg Lys Pro Cys 99:9 INFORMATION FOR SEQ ID 1 5(i) SEQUENCE CHARACTERISTICS: 99 LENGTH: 92 amino acids TYPE: amino acid STRANDEDNESS: single 99999(D) TOPOLOGY: linear *99 (ii) MOLECULE TYPE: protein FRAGMENT TYPE: internal (xi) SEQUENCE DESCRIPTION: SEQ ID Trp Tyr His Ser Ser Leu Thr Arg Giu Giu Ala Giu Ara Lys Leu Tyr 1 5 10 Ser Gly Ala Gin Thr Asp Gly Lys Phe Leu Leu Arg Pro Ara Lys Giu 25 Gin Gly Thr Tyr Ala Leu Ser Leu Ile Tyr Gly Lys Thr Val Tyr His 40 Tyr Leu Ile Ser Gin Asp Lys Ala Gly Lys Tyr Cys Ile Pro Giu Gly 55 Thr Lys Phe Asp Thr Leu Trp Gin Leu Val Glu Tyr Leu Lys Leu Lys 461 70 75 Ala Asp Gly Leu lie Tyr Cys Leu Lys Glu Ala Cys 9 .9 9 99*9 462

Claims (12)

1. A composition comprising a protein in crystalline form containing a peptide sequence comprising a tandem SH2 region of a ZAP family protein or a portion thereof.

2. A composition of claim 1 which further comprises one or more heavy metal atoms.

3. A composition of claim 1 wherein the protein comprises a region characterized by the coordinates of Appendix I, Appendixll, Appendix III, or Appendix IV, or coordinates having a 1 0 root mean square deviation therefrom, with respect to backbone atoms of the listed amino acids, of not more than 1.5 A.

4. A composition of claim 1 in which the protein is in a complex with one or more ligand molecules.

5. A composition of claim 1 in which the protein comprises the tandem SH2 region of human ZAP-70 (spanning at least amino acid residues 3 through 279) or the tandem SH2 region of human SYK (spanning at least amino acid residues 6 through 265).

6. A composition of any of claims 1-5 which diffracts x-rays to a resolution of greater than about 3.5 A. g* A method for determining the three-dimensional structure of a protein containing an SH2 domain, or a co-complex of the protein with a ligand therefor, which comprises obtaining x-ray diffraction data for crystals of the protein or co-complex, c a providing three-dimensional structural coordinates for a composition of any of claims 1-6, and determining the three-dimensional structure of the SH2 domain-containing protein or co-complex by analyzing the x-ray diffraction data with reference to the previous structural coordinates using molecular replacement.

8. A method of claim 7 wherein the protein is a co-complex of ZAP-NC, or a portion thereof, with a ligand other than the i1 peptide.

9. A method of claim 7 wherein the protein is a co-complex of SYK-NC, or a portion thereof, with a ligand therefor. 463 A method for determining the three dimensional structure of a protein containing an SH2 domain or co-complex of said protein with a ligand therefor, which method comprises: providing structural coordinates for a composition of any of claims 1-6, and determining the three-dimensional structure of the SH2 domain-containing protein or co-complex by homology modeling with reference to the previous structural coordinates.

11. A method for selecting a compound capable of binding to a ZAP family protein which comprises: g providing coordinates defining the three dimensional structure of a ZAP family 1 5 protein or a portion thereof; characterizing points associated with that three dimensional structure with respect to the favorability of interactions with one or more selected functional groups; oooo eo 20 providing a database of one or more candidate compounds; and identifying from the database those compounds having structures which best fit ***the points of favorable interaction with the three dimensional structure.

12. A method of claim 11 which further comprises testing a compound so identified for its ability to: bind to a ZAP family protein, inhibit the binding of a ZAP family protein to a natural or non-natural ligand therefor, and/or inhibit a biological function mediated by a ZAP family member.

13. A machine-readable data storage medium, comprising a data storage material encoded with machine readable data which, when using a machine programmed with instructions for using said data, is capable of displaying a graphical three-dimensional representation of a molecule or molecular complex comprising a protein of any of claims 1-6, or a portion thereof.

464- 14. A machine-readable data storage medium, comprising a data storage material encoded with machine readable data which, when using a machine programmed with instructions for using said data, is capable of displaying a graphical three-dimensional representation of a ZAP family protein or ZAP family protein:ligand complex or portion thereof based on the coordinates of Appendix I, Appendix II, or Appendix III, or based on coordinates having a root mean square deviation therefrom with respect to conserved protein backbone atoms of not more than 1.5 A. A machine-readable data storage medium comprising a data storage material encoded 1 0 with a first set of machine readable data which, when combined with a second set of machine- readable data, using a machine programmed with instructions for using said first set of data and said second set of data, can determine at least a portion of the coordinates corresponding to the second set of machine-readable data, wherein: said first set of data comprises a Fourier transform of at least a portion of the coordinates according to Appendix I, Appendix II, 15 Appendix III or Appendix IV; and said second set of data comprises an X-ray diffraction pattern of a molecule or molecular complex. S. 16. A method for displaying a three dimensional representation of a composition of any of claims 1-6 which comprises: providing a machine capable of reading data stored on a machine-readable storage medium of claim 13, programmed with instructions for using said data to display a ~graphical three-dimensional representation of a protein or protein:ligand complex or portion thereof defined by said data, and loaded with a machine-readable storage medium of claim 13: and, S 25 permitting the machine to read said data and display the three-dimensional representation. 17. A method for designing a compound capable of binding to a ZAP family protein that comprises: graphically displaying a three-dimensional representation based on coordinates defining the three-dimensional structure of a ZAP family protein or a portion thereof; characterizing the interactions between portions of a ligand that is known to bind to the protein to identify candidate moieties for replacement; providing a knowledge base of one or more candidate substitute moieties; and 465 identifying from the knowledge base one or more substitute moieties which may be used to replace one or more selected portions of the ligand and retain at least a portion of the ligand's binding affinity for the protein. 18. A method for designing a compound capable of binding to a ZAP family protein that comprises: providing coordinates defining the three-dimensional structure of a ZAP family protein or a portion thereof; characterizing points associated with that three-dimensional structure to identify preferred points with respect to the favorability of interactions of one or more selected functional groups with the protein; 15 characterizing one or more portions of a ligand that is known to bind to the protein that are proximal to the characterized points; providing a knowledge base of one or more molecular fragments or molecules; Ioo o a 20 identifying from the knowledge base one or more fragments or molecules that permit connection of preferred points identified in to portions of the ligand; and modifying the structure of the ligand by the covalent attachment thereto of one or more such fragments or molecules so identified in an orientation and location selected to permit the modified ligand to bind to the protein. 19. A method for determining the orientation of a ligand bound to a ZAP family protein that comprises: providing coordinates defining the three-dimensional structure of a ZAP family protein or a portion thereof; characterizing points associated with that three-dimensional structure to identify preferred points with respect to the favorability of interactions of one or more selected functional groups with the protein; anchoring one or more functional groups of a ligand known to bind to the protein, the bound conformation of the ligand being unknown, at selected sites consistent with the preferred points of functional group interaction identified in and, 466 performing modeling calculations to generate a series of alternative conformations and/or orientations for the anchored ligand. 20. A method for designing a compound capable of binding to a ZAP family protein that comprises: selecting a protein:ligand conformation and/or orientation identified by the method of claim 19; characterizing the interactions between portions of the ligand and the protein to identify candidate moieties of the ligand for replacement; providing a knowledge base of one or more candidate substitute moieties; and 1 identifying from the knowledge base one or more substitute moieties which may be used to replace one or more selected portions of the ligand and retain at least a portion of the ligand's binding affinity for the protein. o* 20 21. A method for designing a compound capable of binding to a ZAP family protein that comprises: selecting a protein:ligand conformation and/or orientation identified by the method of claim 19; characterizing points associated with the three-dimensional structure of the protein to identify preferred points with respect to the favorability of interactions of one or more selected functional groups with the protein; characterizing one or more portions of a ligand that is known to bind to the protein that are proximal to the characterized points; providing a knowledge base of one or more molecular fragments or molecules; identifying from the knowledge base one or more fragments or molecules that permit connection of preferred points identified in to portions of the ligand; and 467 modifying the structure of the ligand by the covalent attachment thereto of one or more such fragments or molecules so identified in an orientation and location selected to permit the modified ligand to bind to the protein. 22. A method for selecting or designing a compound capable of binding to a ZAP family protein that comprises any combination of steps as described in claims 17-21. DATED this 8th day of September, 2000 ARIAD PHARMACEUTICALS, INC. by its Patent Attorneys DAVIES COLLISON CAVE o 468