WO2005052147A2

WO2005052147A2 - Method of screening for a modulator of cdk4

Info

Publication number: WO2005052147A2
Application number: PCT/GB2004/004793
Authority: WO
Inventors: Campbell Mcinnes; Mark Thomas; Shudong Wang; Janice Mclachlan; Christopher Meades; George Kontopidis; Gavin Wood; Peter Fischer
Original assignee: Cyclacel Limited
Priority date: 2003-11-25
Filing date: 2004-11-11
Publication date: 2005-06-09
Also published as: WO2005052147A3; GB0327380D0

Abstract

The present invention relates to a homology model for CDK4, and the use thereof in assays for the identification of small molecule CDK4 modulators. The invention further relates to CDK4 modulators identified by said assays, and their use in the treatment of CDK4-related disorders such as proliferative disorders.

Description

METHOD

The present invention relates to cyclin dependent kinases (CDKs) and small molecule inhibitors thereof. More specifically, the invention relates to CDK4 inhibitors, and a method for designing and identifying small molecule CDK4 inhibitors using a homology model for CDK4.

BACKGROUND TO THE INVENTION

The cyclin dependant kinases (CDKs) are key regulators of progression through the various stages of the eukaryotic cell cycle. It lias been shown that over-expression and/or loss of function of key proteins implicated in the chain of events upstream and downstream of the CDKs leads to tumorigenesis and neoplastic transformation. This includes the cyclins (positive regulatory subunits), the natural inhibitory proteins, pl6/pl9, p21Kip and p27Waf and also the downstream targets of CDK phosphorylation, i.e. the retinoblastoma protein and the E2F family. In each case, pharmacological inhibition of cyclin dependant kinase activity should lead to restoration ofthe cell cycle checkpoints and in addition potentially trigger cell death via apoptosis. It can thus be seen that these enzymes represent interesting pharmaceutical targets since tumours arising from a number of different gene mutations could be treated using kinase inhibitors specific for the CDKs. While at present nine CDK isoforms have been identified and characterised, the main focus of cancer therapy to date has been on CDK4, 6/cyclin D (Gl phase), CDK2/cyclin A, E (Gl and S phase) and CDKl/cyclin B (G2/M phase). The primary method for CDK inhibition has been to develop small molecules that compete with ATP binding to the kinase, however an alternate approach currently being investigated is to block recruitment of macromolecular substrates to the complex. While there are numerous examples of very potent CDK2 and CDK4 ATP competitive ihhibitors, very few compounds have ^• progressed past the preclinical stage. There is therefore tremendous scope for further development of new classes of CDK inhibitor, including those that specifically target the individual kinase isoforms and which may exhibit a less general cytotoxic effect and better side effect profile. CDK4/cyclin DI has been demonstrated to play a critical role early in interphase at the Go/Gl Gap phase of the cell cycle. It is thought that this represents a viable target for anti-tumour therapy, as kinase inhibition would lead to cell cycle anest via maintenance of the Rb protein in its hypophosphorylated state in which it remains complexed with E2F1/DP1 thereby preventing transcription of genes necessary for the progression into S-phase ofthe cell cycle.

The present invention seeks to elucidate small molecule CDK4 inhibitors, and in particular, provides a method for designing and identifying such inhibitors. To date, although there have been reports of ATP competitive compounds that bind selectively to

CDK4, there has been little discussion of the factors which contribute to CDK4 potency and selectivity.

The invention also seeks to elucidate further information on the 3-dimensional structure of the CDK4 ATP binding domain and the nature ofthe binding interactions between CDK4 and small molecule inhibitors. More specifically, the invention seeks to provide small molecule inhibitors that are selective for CDK4 over other CDKs.

STATEMENT OF INVENTION

The present invention relates to a homology model for CDK4, and the use thereof in the indentification.of small molecule CDK4 inhibitors.

As used herein, the term "model" refers to a structural model such as a three dimensional (3D) structural model (or representation thereof) comprising CDK4. Preferably, the model comprising CDK4 is built from all or a portion of the structure co-ordinates presented in Table 1. The homology model of the invention enables candidate compounds to be identified that bind spatially and preferentially to CDK4, particularly to the active site of CDK4.

Aspects of the invention are presented in the accompanying claims and are further described in the following paragraphs. DETAILED DESCRIPTION

GENERATION OF THE CDK4 HOMOLOGY STRUCTURE

A number of compounds have been described in the literature that show preferential binding to CDK4. However, to date there has been no significant progress in determining the structural features required for selectivity towards CDK4. A major reason for this lack of insight has been the paucity of structural information for this isoform. In contrast, there is a plethora of structural data for CDK2 as it has been crystallised in many forms including in complex with Cyclin A and p27 and as inhibitor complexes with the monomeric and cyclin activated forms. Two approaches have been utilised in obtaining stractural information and to generate binding modes for CDK4 inhibitory molecules. These include (1) structures derived from sequence homology with CDK2 and CDK6 and (2) crystallising monomeric CDK2, where the residues differing in the ATP binding pocket have been replaced with the conesponding residues ofthe CDK4 active site.

The present invention employs the homology modelling approach in conjunction with automated flexible docking methods to generate a set of binding hypotheses for the ligand-CDK4 complexes of a number of known inhibitors. Based on analysis of the sequence and residues lining the ATP binding pocket, it was possible to detennine the specific residues and side chains which differ in the CDK4 structure and to identify the interactions that could be exploited in the design of selective compounds. This information could be used in two ways, both in the enhancement of CDK4 selectivity and in the engineering of molecules with reduced binding to CDK4 and tighter specificity for CDK2. The residues comprising the ATP cleft of both CDK2 and CDK4 are compared in Table 3. As can be seen, the key differences are in residues, T102 and in E144. The other changes include the H95 and V96 replacements for the hinge region H-bonding interacting residues. However, as these residues provide contacts through the backbone, they would not be expected to impact inhibitor binding significantly. The electrostatic surface of the ATP binding sites of CDK2 and CDK4 are compared in Figure 1. As can be seen the composition of the two binding pockets differs considerably due to the non-conservative changes in key ATP and inhibitor contacting residues (see Table 3).

ASSAYS BASED ON THE CDK4 HOMOLOGY MODEL A first aspect ofthe invention relates to a method of screening for a modulator of CDK4, wherein the method comprises using the structure co-ordinates of Table 1.

Since no experimental three-dimensional structures of CDK4 kinase domains are known, a CDK4 kinase domain homology model was constructed.

Preferred embodiments ofthe invention will now be described.

In one prefened embodiment ofthe invention, the method comprises the steps of: (a) providing at least a portion ofthe structure co-ordinates of Table 1; (b) employing at least a portion ofthe structure co-ordinates of Table 1 to design or select or synthesise a putative modulator of CDK4; (c) contacting the putative modulator of CDK4 with CDK4 or a mutant, variant, homologue, derivative or fragment thereof, in the presence of a substrate of CDK4; and (d) determining whether said putative modulator of CDK4 modulates CDK4.

hi a prefened embodiment, at least a portion of the structure co-ordinates of Table 1 and/or the putative modulator of CDK4 and/or the substrate are provided on a machine- readable data storage medium comprising a data storage material encoded with machine readable data.

hi a prefened embodiment, the putative modulator of CDK4 is selected from a library of compounds. Preferably, the library is an in silico library. Suitable in silico libraries will be familiar to those skilled in the art, and include the Available Chemical Directory (MDL Inc), the Derwent World Drug Index (WDI), BioByteMasterFile, the National Cancer Institute database (NCI), and the Maybridge catalogue. In another prefened embodiment, the putative modulator of CDK4 is selected from a database.

In another prefened embodiment, the putative modulator of CDK4 is designed de novo.

In yet another prefened embodiment, the putative modulator of CDK4 is designed from a known CDK4 modulator.

In one prefened embodiment, the modulator of CDK4 is selective for CDK4 over CDK2.

Preferably, the design or selection of the putative modulator of CDK4 is performed in conjunction with computer modelling.

In one particularly prefened embodiment, the putative modulator of CDK4 inhibits CDK4 activity.

In a further prefened embodiment, the putative modulator of CDK4 is useful in the prevention and/or treatment of a CDK4 related disorder.

Even more preferably, the CDK4 related disorder is a proliferative disorder.

More preferably still, the proliferative disorder is selected from cancer, leukemia, glomemlonephritis, rheumatoid arthritis, psoriasis and chronic obstructive pulmonary disorder.

A second aspect ofthe invention relates to an assay for a candidate compound capable of modulating CDK4, said assay comprising the steps of:

(a) contacting said candidate compound with CDK4;

(b) detecting whether said candidate compound forms associations with one or more amino acid residues conesponding to CDK4 amino acid residues V20, F93, D99, L147, E144 and D158. In one prefened embodiment, said candidate compound is selected by performing rational drug design with a 3-dimensional model of CDK4 in conjunction with computer modelling.

A third aspect of the invention relates to the use of a compound selected from the following:

IH PI [61

17] [8] [9]

or a pharmaceutically acceptable salt thereof, in an assay for identifying candidate compounds capable of selectively modulating CDK4.

As used throughout, the term "selectively" refers to modulators or candidate compounds that are selective for CDK4. Preferably the modulators are selective for CDK4 over CDK2. Preferably the modulators of the invention have a selectivity ratio for CDK4 over CDK2 of greater than 2, more preferably greater than 5, more preferably still greater than 10. Even more preferably, the selectivity ratio for CDK4 over CDK2 is greater than 25, or more preferably still greater than 50 or 100. Selectivity ratios may readily be determined by the skilled person.

Preferably, the assay is a competitive binding assay. More preferably, the assay comprises contacting a candidate compound with CDK4 in the presence of a compound of formula [1], [2], [6]-[9] as defined above, or a pharmaceutically acceptable salt thereof, and detecting any change in the interaction between said compound of formula [1], [2], [6]-[9] and CDK4.

Another aspect ofthe invention relates to a computer for producing a three-dimensional representation of CDK4 wherein said computer comprises:

(a) a computer-readable data storage medium comprising a data storage material encoded with computer-readable data, wherein said data comprises the structure co-ordinates of Table 1;

(b) a working memory for storing instructions for processing said computer- readable data;

(c) a central-processing unit coupled to said working memory and to said computer- readable data storage medium for processing said computer-machine readable data into said three-dimensional representation; and

(d) a display coupled to said central-processing unit for displaying said three- dimensional representation.

Another aspect of the invention relates to a machine-readable data storage medium comprising a data storage material encoded with machine readable data, wherein the data is defined by at least a portion ofthe structure co-ordinates of Table 1.

A further aspect of the invention relates to the use of the above-described computer or machine readable data storage medium to predict the structure and/or function of potential modulators of CDK4.

Another aspect relates to the use of at least a portion of the structure co-ordinates of Table 1 to screen for modulators of CDK4.

A further aspect relates to the use of at least a portion of the structure co-ordinates of Table 1 to solve the structure of the crystalline form of any other protein with significant amino acid sequence homology to any functional domain of CDK4. Preferably, the structure of the crystalline form of any other protein with significant amino acid sequence homology to any functional domain of CDK4 is solved using molecular replacement.

Yet another aspect of the invention relates to the use of at least a portion of the structure co-ordinates of Table 1 in molecular design techniques to design, select and synthesise modulators of CDK4.

A further aspect of the invention relates to the use of at least a portion of the structure co-ordinates of Table 1 in the development of compounds that can isomerise to reaction intermediates in the chemical reaction of a substrate or other compound that binds to CDK4.

Another aspect of the invention relates to the use of at least a portion of the stmcture co-ordinates of Table 1 to screen small molecule databases for chemical entities or compounds that modulate CDK4.

Preferably, the modulator of CDK4, chemical entity, substrate or compound selectively inhibits CDK4.

CDK4 MODULATORS

A further aspect ofthe invention relates to a CDK4 modulator identified by the above- described method, or a candidate compound identified by the above-described assay.

Preferably, the CDK4 modulator or candidate compound ofthe invention inhibits CDK4 activity.

More preferably, the CDK4 modulator or candidate compound of the invention selectively inhibits CDK4.

In one particularly prefened embodiment, the CDK4 modulator or candidate compound of the invention has an ionizable functional group capable of forming associations with the amino acid residues conesponding to CDK4 amino acid residues D99 and El 44 of

CDK4. More preferably still, the ionizable functional group is a group which is positively charged at physiological pH. Even more preferably, the ionizable functional group is an

NH group which is positively charged at physiological pH.

In one prefened embodiment, the CDK4 modulator or candidate compound of the invention comprises a functional group capable of forming a hydrogen bond with the amino acid residue conesponding to D 158 of CDK4.

In one prefened embodiment, the CDK4 modulator or candidate compound of the invention is capable of forming associations with one or more amino acid residues conesponding to V20, D99 and L147 of CDK4.

In one prefened embodiment, the CDK4 modulator or candidate compound of the invention comprises a group which is capable of sterically interacting with the amino acid residues conesponding to D86 and K89 ofthe ATP binding site of CDK2.

In a prefened embodiment, the CDK4 modulator or candidate compound of the invention is an ineversible antagonist.

The present invention permits the use of molecular design techniques to design, select and synthesise chemical entities and compounds, including CDK4 modulating compounds, capable of binding to CDK4, in whole or in part.

By way of example, the structure co-ordinates of Table 1 may be used to design compounds that bind to CDK4 and may alter the physical properties of the compounds (eg. solubility) or CDK4 itself. This invention may be used to design compounds that act as modulators, such as competitive inhibitors - of CDK4 by binding to all or a portion of the active site of CDK4. Compounds may also be designed that act as non- competitive inhibitors of CDK4. These non-competitive inhibitors may bind to all or a portion of CDK4 already bound to its substrate and may be more potent and specific than known CDK4 inhibitors that compete only for the CDK4 active site. Similarly, non-competitive inhibitors that bind to and inhibit CDK4 whether or not it is bound to another chemical entity may be designed using the structure co-ordinates of CDK4 described herein.

The present invention may also allow the development of compounds that can isomerise to reaction intermediates in the chemical reaction of a substrate or other compound that binds to CDK4. Thus, the time-dependent analysis of structural changes in CDK4 during its interaction with other molecules may be performed. The reaction intermediates of CDK4 may also be deduced from the reaction product in co- complex with CDK4. Such information is especially useful to design improved analogues of known CDK4 modulators or to design new CDK4 modulators based on the reaction intermediates of the CDK4 enzyme and CDK4 -modulator complex. This may provide a new route for designing CDK4 modulators with high specificity and stability. Preferably, this provides a new route for designing CDK4 modulators with high specificity, high stability and low toxicity.

Small molecule databases or candidate compounds may be screened for chemical entities or compounds that can bind in whole, or in part, to CDK4. Thus, in a prefened embodiment, the putative CDK4 modulator is from a library of compounds or a database. In this screening, the quality of fit of such entities or compounds to the binding site may be judged by various methods - such as shape complementarity or estimated interaction energy (Meng, E. C. et al., J. Comp. Chem., 13, pp. 505-524 (1992)).

The structure co-ordinates of Table 1, or portions thereof, may also be useful in solving the structure of crystal forms of CDK4. They may also be used to solve the structure of CDK4 mutants, CDK4 variants, CDK4 homologues, CDK4 derivatives, CDK4 fragments and CDK4 complexes.

Preferably, the stmcture co-ordinates of Table 1 may be used to solve the stmcture of the crystalline form of proteins having significant amino acid sequence homology to any functional domain of CDK4. By way of example, molecular replacement may be used. In this method, the unknown crystal structure, whether it is a crystal form of

CDK4, a CDK4 mutant, a CDK4 variant, a CDK4 homologue (eg. another protein with significant amino acid sequence homology to any functional domain of CDK4), a

CDK4 derivative, a CDK4 fragment or a CDK4 co-complex may be determined using the CDK4 structure co-ordinates of the present invention. This method will provide a more accurate structural form for the unknown crystal more quickly and efficiently than attempting to determine such information ab initio.

In a prefened embodiment of the present invention, the CDK4 crystal of unknown structure further comprises an entity bound to the CDK4 protein or a portion thereof, for example, an entity that is an inhibitor of CDK4.

The crystal stmctures of such complexes may be solved by molecular replacement or in combination with MAD (Multiwavelength Anomalous Dispersion) and/or MIRAS (Multiple Isomorphous Replacement with Anomalous Scattering) procedures - and compared with that of wild-type CDK4. Potential sites for modification within the binding sites of the enzyme may thus be identified. This information provides an additional tool for determining the most efficient binding interactions, for example, increased hydrophobic interactions, between CDK4 and a chemical entity or compound.

The structures and complexes of CDK4 may be refined using computer software - such as X-PLOR (Meth. Enzymol., vol. 114 & 115, H. W. Wyckoff et al., eds., Academic Press (1985)), MLPHARE (Collaborative computational project Number 4. The CCP4 Suite: Programs for Protein Crystallography (1994) Acta Crystallogr. D 50, 760-763) and SHARP [De La Fortelle, E. & Bricogne, G. Maximum-likelihood heavy-atom parameters refinement in the MIR and MAD methods (1997) Methods Enzymol. 276, 472-494). Preferably, the complexes are refined using the program CNS (Briinger et al. (1998) Acta Crystallogr. D 54, 905-921). During the final stages of refinement water molecules, ions and inhibitor molecules may be inserted in the structure. This information may thus be used to optimise known classes of CDK4 modulators, eg. CDK4 inhibitors, and more importantly, to design and synthesise novel classes of CDK4 modulators. The overall figure of merit may be improved by iterative solvent flattening, phase combination and phase extension with the program SOLOMON [Abrahams, J. P. &

Leslie, A. G. W. Methods used in stmcture detenriination of bovine mitochondrial FI

ATPase. (1996) Acta Crystallogr. D 52, 110-119].

The structure co-ordinates of the homology model of the present invention may also facilitate the identification of related proteins or enzymes analogous to CDK4 in function, structure or both, thereby further leading to novel therapeutic modes for treating or preventing CDK4 related diseases.

The design of compounds that bind to or modulate CDK4 according to the present invention generally involves consideration of two factors. Firstly, the compound must be capable of physically and stracturally associating with CDK4. Non-covalent molecular interactions important in the association of CDK4 with its substrate may include hydrogen bonding, van der Waals and hydrophobic interactions. Secondly, the compound must be able to assume a conformation that allows it to associate with CDK4. Although certain portions of the compound may not directly participate in the association with CDK4, those portions may still influence the overall conformation of the molecule. This may have a significant impact on potency. Such conformational requirements include the overall three-dimensional structure and orientation of the chemical entity or compound in relation to all or a portion of a binding site of CDK4, or the spacing between functional groups of a compound comprising several chemical entities that directly interact with CDK4.

The potential modulating or binding effect of a chemical compound on CDK4 may be analysed prior to its actual synthesis and testing by the use of computer modelling techniques. If the theoretical structure of the given compound suggests insufficient interaction and association with CDK4, then synthesis and testing of the compound may be obviated. However, if computer modelling indicates a strong interaction, the molecule may be synthesised and tested for its ability to bind to CDK4 and modulate (eg. inhibit) using the fluorescent substrate assay of Thornberry et al. (2000) Methods Enzymol. 322, pp 100-110. In this manner, synthesis of inactive compounds may be avoided.

A modulating or other binding compound of CDK4 may be computationally evaluated and designed by means of a series of steps in which chemical entities or candidate compounds are screened and selected for their ability to associate with CDK4.

A person skilled in the art may use one of several methods to screen chemical entities or candidate compounds for their ability to associate with CDK4 and more particularly with the individual binding sites of CDK4. This process may begin by visual inspection of, for example, the active site on the computer screen based on the CDK4 co-ordinates of the present invention. Selected chemical entities or candidate compounds may then be positioned in a variety of orientations, or docked, with CDK4. Docking may be accomplished using software such as Quanta and Sybyl, followed by energy minimisation and molecular dynamics with standard molecular mechanics force fields - such as CHARMM and AMBER.

Specialised computer programs may also assist in the process of selecting chemical entities or candidate compounds. These include but are not limited to MCSS (Miranker and Karplus (1991) Proteins: Stmcture, Function and Genetics, 11, pp. 29-34); GRID (Goodford (1985) J. Med. Chem., 28, pp. 849-857) and AUTODOCK (Goodsell and Olsen (1990), Proteins: Stracture. Function, and Genetics, 8, pp. 195-202.

Once suitable chemical entities or candidate compounds have been selected, they may be assembled into a single compound, such as a CDK4 modulator. Assembly may proceed by visual inspection of the relationship of the chemical entities or candidate compounds in relation to the structure co-ordinates of CDK4. This may be followed by manual model building using software - such as Quanta, Sybyl, O, HOOK or CAVEAT [Jones, T. A., Zou, J. Y., Cowan, S. W. & Kjeldgaard, M. Improved methods for building protein models in electron density maps and the location of enors in these models (1991) Acta Crystallogr. A 47, 110-119]. Refinement ofthe model may be carried out using the program CNS [Briinger, A. T. et al. Crystallography & NMR System: A new software suite for macromolecular stmcture determination. (1998) Acta Crystallogr. D 54, 905-921].

Various programs may be used by a skilled person to connect the individual chemical entities or candidate compounds, such as 3D Database systems (Martin (1992) J Med. Chem., 35, pp. 2145-2154) and CAVEAT (Bartlett et al (1989) Royal Chem. Soc. 78, pp. 182-196).

Rather than build a CDK4 inhibitor one chemical entity at a time, modulating or other CDK4 binding compounds may be designed as a whole or de novo using either an empty binding site or optionally including some portion(s) of a known inhibitor(s). Such compounds may be designed using programs that may include but are not limited to LEGEND (Nishibata and Itai (1991) Tetrahedron, 47, p. 8985) and LUDI (Bohm (1992) J. Comp. Aid. Molec. Design, 6, pp. 61 -78).

Other molecular modelling techniques may also be employed in accordance with this invention — such as those described by Cohen et al., J. Med. Chem., 33, pp. 883-894 (1990); Navia and Murcko (1992) Cunent Opinions in Stractural Biology, 2, pp. 202- 210 (1992).

Once a compound has been designed or selected by the above methods, the efficiency with which that compound may bind to CDK4 may be computationally evaluated. Specific computer software may be used to evaluate the efficiency of binding (eg. to evaluate compound deformation energy and electrostatic interaction), such as QUANTA/CHARMM (Accelrys Inc., USA) and Insight II Discover (Biosym Technologies Inc., San Diego, Calif., USA). These programs may be implemented, for instance, using a suitable workstation. Other hardware systems and software packages will be known to those persons skilled in the art.

Once a CDK4-modulating compound has been selected or designed, as described above, substitutions may be made (eg. in atoms or side groups) to improve or modify the binding properties. The substitutions may be conservative ie. the replacement group may have approximately the same size, shape, hydrophobicity and charge as the original group. Such substituted chemical compounds may then be analysed for efficiency of binding to CDK4 by the same computer methods described above.

Candidate compounds and modulators of CDK4 etc. which are identified using the methods of the present invention may be screened in assays. Screening can be, for example in vitro, in cell culture, and/or in vivo. Biological screening assays preferably centre on activity-based response models, binding assays (which measure how well a compound binds), and bacterial, yeast and animal cell lines (which measure the biological effect of a compound in a cell). The assays can be automated for high capacity-high throughput screening (HTS) in which large numbers of compounds can be tested to identify compounds with the desired activity.

Cunent screening technologies are described in Handbook of Drag Screening, edited by Ramakrishna Seethala, Prabhavathi B. Fernandes. New York, NY, Marcel Dekker, (2001).

MODULATING CDK4 As herein, the term "modulating" or "modulates" refers to preventing, suppressing, inhibiting, alleviating, restorating, elevating, increasing or otherwise affecting CDK4.

The term "CDK4 modulator" may refer to a single entity or a combination of entities.

The CDK4 modulator may be an antagonist or an agonist of CDK4.

As used herein, the term "agonist" means any entity, which is capable of interacting (eg. binding) with CDK4 and which is capable of increasing a proportion of the CDK4 that is in an active form, resulting in an increased biological response.

As used herein, the term "antagonist" means any entity, which is capable of interacting (eg. binding) with CDK4 and which is capable of decreasing (eg. inhibiting) a proportion of the CDK4 that is in an active form, resulting in a decreased biological response.

Preferably, the CDK4 modulators ofthe present invention are antagonists of CDK4.

The modulator of CDK4 may be an organic compound or other chemical. The modulator of CDK4 may be a compound, which is obtainable from or produced by any suitable source, whether natural or artificial. The modulator of CDK4 may be an amino acid molecule, a polypeptide, or a chemical derivative thereof, or a combination thereof. The modulator of CDK4 may even be a polynucleotide molecule, which may be a sense or an anti-sense molecule. The modulator of CDK4 may even be an antibody.

The modulator of CDK4 may be designed or obtained from a library of compounds, which may comprise peptides, as well as other compounds, such as small organic molecules.

By way of example, the modulator of CDK4 may be a natural substance, a biological macromolecule, or an extract made from biological materials such as bacteria, fungi, or animal (particularly mammalian) cells or tissues, an organic or an inorganic molecule, a synthetic agent, a semi-synthetic agent, a structural or functional mimetic, a peptide, a peptidomimetic, a derivatised agent, a peptide cleaved from a whole protein, or a peptide synthesised synthetically (such as, by way of example, either using a peptide synthesiser or by recombinant techniques or combinations thereof, a recombinant agent, an antibody, a natural or a non-natural agent, a fusion protein or equivalent thereof and mutants, derivatives or combinations thereof).

Typically, the modulator of CDK4 will be an organic compound. Typically, the organic compounds will comprise two or more hydrocarbyl groups. Here, the term "hydrocarbyl group" means a group comprising at least C and H and may optionally comprise one or more other suitable substituents. Examples of such substituents may include halo-, alkoxy-, nitro-, an alkyl group, a cyclic group etc. In addition to the possibility of the substituents being a cyclic group, a combination of substituents may form a cyclic group. If the hydrocarbyl group comprises more than one C then those carbons need not necessarily be linked to each other. For example, at least two of the carbons may be linked via a suitable element or group. Thus, the hydrocarbyl group may contain hetero atoms. Suitable hetero atoms will be apparent to those skilled in the art and include, for instance, sulphur, nitrogen and oxygen. For some applications, preferably the modulator of CDK4 comprises at least one cyclic group. The cyclic group may be a polycyclic group, such as a non-fused polycyclic group. For some applications, the modulator of CDK4 comprises at least the one of said cyclic groups linked to another hydrocarbyl group.

The modulator of CDK4 may contain halo groups, for example, fluoro, chloro, bromo or iodo groups, or one or more of alkyl, alkoxy, alkenyl, alkylene and alkenylene groups, each of which may be branched or unbranched.

The modulator of CDK4 may be a stracturally novel modulator of CDK4, or may be an analogue of a known modulator of CDK4.

Preferably, the CDK4 modulators have improved properties over those previously available, for example, fewer side effects.

The modulator of CDK4 may be a mimetic, or may be chemically modified.

The modulator of CDK4 may be capable of displaying other therapeutic properties.

The modulator of CDK4 may be used in combination with one or more other pharmaceutically active agents. If combinations of active agents are administered, then they may be administered simultaneously, separately or sequentially. CANDIDATE COMPOUNDS

As used herein, the term "candidate compound" includes, but is not limited to, a compound which may be obtainable from or produced by any suitable source, whether natural or not.

The candidate compound may be designed or obtained from a library of compounds, which may comprise peptides, as well as other compounds, such as small organic molecules and particularly new lead compounds. By way of example, the candidate compound may be a natural substance, a biological macromolecule, or an extract made from biological materials - such as bacteria, fungi, or animal (particularly mammalian) cells or tissues, an organic or an inorganic molecule, a synthetic candidate compound, a semi-synthetic candidate compound, a structural or functional mimetic, a peptide, a peptidomimetic, a derivatised candidate compound, a peptide cleaved from a whole protein, or a peptide synthesised synthetically, for example, either using a peptide synthesiser or by recombinant techniques or combinations thereof, a recombinant candidate compound, a natural or a non-natural candidate compound, a fusion protein or equivalent thereof and mutants, derivatives or combinations thereof. The candidate compound may even be a compound that is a modulator of CDK4, such as a known inhibitor of CDK4, that has been modified in some way eg. by recombinant DNA techniques or chemical synthesis techniques.

Typically, the candidate compound will be prepared by recombinant DNA techniques and/or chemical synthesis techniques.

Once a candidate compound capable of interacting CDK4 has been identified, further steps may be carried out to select and/or to modify the candidate compounds and/or to modify existing compounds, such that they are able to modulate CDK4.

In one aspect, the modulator of CDK4 may act as a model (for example, a template) for the development of other compounds . A further aspect relates to the use of candidate compounds or CDK4 modulators identified by the assays and methods ofthe invention in one or more model systems, for example, in a biological model, a disease model, or a model for CDK4 inhibition. Such models may be used for research purposes and for elucidating further details of the biological, physicochemical, pharmacological and/or pharmacokmetic activity of a particular candidate compound. By way of example, the candidate compounds or

CDK4 modulators of the present invention may be used in biological models or systems in which the cell cycle is known to be of particular significance, e.g. in models relating to cell fertilization, especially in animals.

MIMETIC

As used herein, the term "mimetic" relates to any chemical which includes, but is not limited to, a peptide, polypeptide, antibody or other organic chemical which has the same qualitative activity or effect as a known compound. That is, the mimetic is a functional equivalent of a known compound.

CHEMICAL SYNTHESIS METHODS

Preferably, the modulator of CDK4 of the present invention may be prepared by chemical synthesis techniques.

It will be apparent to those skilled in the art that sensitive functional groups may need to be protected and deprotected during synthesis of a compound ofthe invention. This may be achieved by conventional techniques, for example as described in "Protective Groups in Organic Synthesis" by T W Greene and P G M Wuts, John Wiley and Sons Inc. (1991), and by P. LKocienski, in "Protecting Groups", Georg Thieme Verlag (1994).

It is possible during some of the reactions that any stereocentres present could, under certain conditions, be racemised, for example if a base is used in a reaction with a substrate having an having an optical centre comprising a base-sensitive group. This is possible during e.g. a guanylation step. It should be possible to circumvent potential problems such as this by choice of reaction sequence, conditions, reagents, protection deprotection regimes, etc. as is weU-known in the art. The compounds and salts may be separated and purified by conventional methods.

Separation of diastereomers may be achieved by conventional techniques, e.g. by fractional crystallisation, chromatography or H.P.L.C. of a stereoisomeric mixture of a compounds or suitable salts or derivatives thereof. An individual enantiomer of a compound may also be prepared from a conesponding optically pure intermediate or by resolution, such as by H.P.L.C. of the conesponding racemate using a suitable chiral support or by fractional crystallisation ofthe diastereomeric salts formed by reaction of the conesponding racemate with a suitably optically active acid or base.

CDK4, modulators of CDK4 or variants, homologues, derivatives, fragments or mimetics thereof may be produced using chemical methods to synthesise the CDK4 or the modulator of CDK4 in whole or in part. For example, a CDK4 peptide or a modulator of CDK4 that is a peptide can be synthesised by solid phase techniques, cleaved from the resin, and purified by preparative high performance liquid chromatography (e.g., Creighton (1983) Proteins Structures And Molecular Principles, WH Freeman and Co, New York NY). The composition ofthe synthetic peptides may be confirmed by amino acid analysis or sequencing (e.g., the Edman degradation procedure; Creighton, supra).

Synthesis of peptides (or variants, homologues, derivatives, fragments or mimetics thereof) may be performed using various solid-phase techniques (Roberge JY et al (1995) Science 269: 202-204) and automated synthesis may be achieved, for example, using the ABI 43 1 A Peptide Synthesizer (Perkin Elmer) in accordance with the instructions provided by the manufacturer. Additionally, the amino acid sequences comprising the modulator of CDK4, may be altered during direct synthesis and/or combined using chemical methods with a sequence from other subunits, or any part thereof, to produce a variant modulator of CDK4.

CHEMICAL MODIFICATION

In one embodiment, the modulator of CDK4 may be a chemically modified modulator of CDK4. The chemical modification of a modulator of CDK4 may either enhance or reduce interactions between the modulator of CDK4 and the target, such as hydrogen bonding interactions, charge interactions, hydrophobic interactions, van der Waals interactions or dipole interactions.

PROCESS

Another aspect ofthe invention relates to a process comprising the steps of:

(a) performing the method according to the invention, or an assay according to the invention;

(b) identifying one or more modulators of CDK4; and (c) preparing a quantity of said one or more CDK4 modulators.

A f rther aspect ofthe invention relates to a process comprising the steps of:

(a) performing the method according to the invention, or an assay according to the invention; (b) identifying one or more CDK4 modulators; and

(c) preparing a pharmaceutical composition comprising said one or more identified CDK4 modulators.

A further aspect relates to a process comprising the steps of: (a) performing the method according to the invention, or an assay according to the invention;

(b) identifying one or more CDK4 modulators;

(c) modifying said one or more CDK4 modulators; and

(d) optionally preparing a pharmaceutical composition comprising said one or more CDK4 modulators.

CDK4 SELECTIVE COMPOUNDS

Studies by the applicant have shown that potent and selective CDK2 ATP competitive compounds can be generated from the 2-phenylamino-4-(thiazol-5-yl)-pyrimidine system. This series, of which the most potent compounds, are in the sub nanomolar range, are generally selective for CDK2. Several of these compounds have been crystallized in complex with CDK2 and the stracture-activity relationship of the pharmacophore has been well characterized. The main determinants for highly potent binding include the H-bond donor acceptor pair from the bridging anilino NH and pyrimidino nitrogen to the hinge region of CDK2; a non polar contact from the thiazole methyl group on the thiazole ring (Phe80), H-bonding contacts from polar substituents on the thiazole (Glu 144) and van der Waals and H-bonds from the pyrimidine and aniline aromatic rings (Vail 8, Asρ86, Lys89, Leul34). The latter group is in the position conesponding to the ionisable group determined in this study to contribute to

CDK4 selectivity. In order to probe the identified determinants for CDK4 selectivity in the context of the aminopyrimidine system, compounds were synthesised which incorporated ionisable groups on the anilino ring of the inhibitor. Table 4 shows the structures of several compounds inco orating methylamine and various substituted piperazine compounds, hi addition, the pKa's were calculated for the primary iom^" sable groups in these substituents. As negative controls, potential inhibitors incorporating a morpholine ring [5\ (isosteric with piperazine) and with an acetylated primary amino group [3] (i.e. both without a substituent capable of forming ion-pair interactions with the Glul44 and Asp99) were synthesised. In addition, the di-anilino compound [4] which has a positively charged group however only below pH5 was tested and found to be non selective for CDK4. Screening of each of these compounds in both CDK2/E and CDK4/D1 kinase assays revealed that only the compounds with an ionisable function exhibited selectivity for CDK4, whereas those without this characteristic on the aniline ring was partially selective for CDK2. In particular, comparison of compounds 5 and 6 which differ by the oxygen to nitrogen replacement in the saturated ring, demonstrates that this simple change results in a more than 20 fold enhancement in CDK4 activity, while the CDK2 inhibition is increased by only two fold. Of the selective inhibitors, compound [9], which was derivitised with a piperazine ring, was the most selective with a 30 fold higher potency in the CDK4/D1 kinase assay. Inhibitors containing methylpiperizine [7] and hydroxyethylpiperizine [8] also exhibited CDK4 selectivity however to a lesser degree.

STRUCTURAL BASIS FOR CDK4 SELECTIVITY

Despite the synthesis of several hundred derivatives, compounds [1], [2], [6], [7], [8] and [9] were the first examples of CDK4 selective compounds in this series of anilino pyrimidines, since the majority ofthe derivatives from this pharmacophore exhibit a 10 fold or greater specificity for CDK2/E. The observed preferential binding of these compounds to CDK4 thus confirmed the initial design hypothesis. As a further test of the hypothesis, the pKa values for the ionisable nitrogens in each ofthe inhibitors were calculated and are shown in Table 4. As can be seen from this table, all the compounds have pKa's of 7 or greater and thus would be partially or fully charged at the pH conditions in which the assay was performed. However, there is no conelation between the basisity of the nitrogen and the extent of observed selectivity for CDK4 therefore suggesting that other determinants additionally contribute to the selectivity. In order to determine all ofthe factors contributing to binding of these compounds to both CDK2 and CDK4, docking with the homology structure and modelling calculations in the context of the available CDK2 complex crystal stmctures were carried out with compounds [1], [5], [6] and [9]. For inhibitor [1], containing an aminomethyl group in the 4 position on the aniline ring, the docked structure showed that it formed the expected binding mode with CDK4 and had similar interaction energies to those observed for other potent CDK4 inhibitors resulting from ion-pair interactions with D99 and El 44. Modeling of the aminomethyl interactions through modification of a known CDK2 inhibitor complex structure from this series demonstrates that much less favourable interaction energies were calculated, resulting from Coulombic and van der Waals repulsion with K89. Comparison of inhibitors [5] and [6] binding to the ATP site of both enzymes is significant in this case, given that they only differ by the NH of the piperazine ring. Overlay of the docked structure of 6 bound to the CDK4 model, with the crystal structure of [5] in complex with CDK2/cyclin A is shown in Figure 2. Energetic analysis suggests as before that the positively charged NH group of the piperazine ring contributes extensively to CDK4 binding through interaction with both D99 and El 44. As can be seen from the overlay, the electrostatic interaction results in the saturated ring moving significantly towards the acidic residues and is displaced with respect to the position of [5] in the CDK2 active site.

Compound [9], having an IC50 of 7 nM on CDK4/D1 was docked into the ATP binding site. The PDB coordinate file of compound [9] is shown in Table 2. The resultant binding mode very closely represented the structure observed with [6] and again was consistent with the crystallographically derived CDK2 complex. The observed pose shows striking complementarity with the ATP cleft and very favourable non-bonded energetics in line with the in vitro potency of this compound. The intermolecular contacts (see Table 5) were also consistent with the selectivity design hypothesis as the evidenced by the charge-charge interactions of the piperazine ring with the side-chains of both D99 and El 44 (Figure 3). The structure also presents evidence for the increase in potency of this compound relative to [6], which only differs in respect to the thiazole substituent. The methylamino group on the thiazole ring of [9], contributes hydrogen bonds to D158 of CDK4 and additionally provides vdW surface complementarity with the cleft. These additional interactions most likely provide the majority of the increase in affinity of this ligand. Analysis of the non- bonded energies for both compounds again corcelated well with in vitro potency.

The docking experiments also provide insight into the potency and selectivity of compounds [7] and [8], having methyl and hydroxy ethyl substituted piperazines respectively. These two inhibitors have a less basic piperazinyl nitrogen and hence would be expected to be less selective for CDK4, however the converse is true. The results suggest that the piperazine substituents provide an increase in potency through vdW contacts with the g carbons of R of CDK4. As discussed previously, the increased selectivity of [7] and [8] is likely the steric consequence of the additional group adjacent to K89 of^* CDK2, resulting in lower affinity for this kinase. The methylated [7] and hydroxyethyl [8] piperazines would therefore bind less potently to CDK2 and be more selective for CDK4. Conversely, [6] and [9], having unsubstituted piperazine rings would have less steric conflict with K89 of CDK2. hi addition, the additional space provided by T 102 (CDK4) in comparison to K89 thus would enable this inhibitor to bind with higher affinity to CDK4.

These results demonstrate conclusively that two major determinants of CDK4 specific binding are (1) the presence of a function in the inhibitor that is positively charged at physiological pH. This functionality results in a more favourable Coulombic energy of interaction between the ATP cleft of CDK4 (D99, El 44) and repels the inhibitor from the active site of CDK2 (K89). (2) A bulky substituent in the volume of the ATP site proximal to K89 and D86. This group precludes effective binding to CDK2 through steric hindrance with these residues and in some cases results in disruption of effective

H-bonds to the hinge region ofthe kinase.

The incorporation of these determinants into a known CDK2 selective molecule facilitates the development of inhibitors that bind preferentially to CDK4/cyclin DI. Alternatively these features can be used to modify non-selective low affinity hits to interact more favourably with this complex.

PHARMACEUTICAL COMPOSITIONS

Another aspect of the invention relates to a pharmaceutical composition comprising a CDK4 modulator or candidate compound of the invention and a pharmaceutically acceptable carrier, diluent, excipient or adjuvant or any combination thereof. Even though the CDK4 modulators or candidate compounds (including their pharmaceutically acceptable salts, esters and pharmaceutically acceptable solvates) can be administered alone, they will generally be administered in admixture with a pharmaceutical carrier, excipient or diluent, particularly for human therapy. The pharmaceutical compositions may be for human or animal usage in human and veterinary medicine.

Examples of such suitable excipients for the various different forms of pharmaceutical compositions described herein may be found in the "Handbook of Pharmaceutical Excipients, 2^nd Edition, (1994), Edited by A Wade and PJ Weller.

Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art, and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (A. R. Gennaro edit. 1985).

Examples of suitable carriers include lactose, starch, glucose, methyl cellulose, magnesium stearate, mannitol, sorbitol and the like. Examples of suitable diluents include ethanol, glycerol and water. The choice of pharmaceutical carrier, excipient or diluent can be selected with regard to the intended route of administration and standard pharmaceutical practice. The pharmaceutical compositions may comprise as, or in addition to, the carrier, excipient or diluent any suitable binder(s), lubricant(s), suspending agent(s), coating agent(s), solubilising agent(s).

Examples of suitable binders include starch, gelatin, natural sugars such as glucose, anhydrous lactose, free-flow lactose, beta-lactose, com sweeteners, natural and synthetic gums, such as acacia, tragacanth or sodium alginate, carboxymethyl cellulose and polyethylene glycol.

Examples of suitable lubricants include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride and the like.

Preservatives, stabilizers, dyes and even flavoring agents may be provided in the pharmaceutical composition. Examples of preservatives include sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid. Antioxidants and suspending agents may be also used.

SALTS/ESTERS

The CDK4 modulators or candidate compounds of the present invention can be present as salts or esters, in particular pharmaceutically acceptable salts or esters.

Pharmaceutically acceptable salts of the CDK4 modulators or candidate compounds of the invention include suitable acid addition or base salts thereof. A review of suitable pharmaceutical salts may be found in Berge et al, J Pharm Sci, 66, 1-19 (1977). Salts are formed, for example with strong inorganic acids such as mineral acids, e.g. sulphuric acid, phosphoric acid or hydrohalic acids; with strong organic carboxylic acids, such as alkanecarboxylic acids of 1 to 4 carbon atoms which are unsubstituted or substituted (e.g., by halogen), such as acetic acid; with saturated or unsaturated dicarboxylic acids, for example oxalic, malonic, succinic, maleic, fumaric, phthalic or tetraphthalic; with hydroxycarboxylic acids, for example ascorbic, glycolic, lactic, malic, tartaric or citric acid; with aminoacids, for example aspartic or glutamic acid; with benzoic acid; or with organic sulfonic acids, such as (Cι-C₄)-alkyl- or aryl- sulfonic acids which are unsubstituted or substituted (for example, by a halogen) such as methane- or p-toluene sulfonic acid.

Esters are formed either using organic acids or alcohols/hydroxides, depending on the functional group being esterified. Organic acids include carboxylic acids, such as alkanecarboxylic acids of 1 to 12 carbon atoms which are unsubstituted or substituted

(e.g., by halogen), such as acetic acid; with saturated or unsaturated dicarboxylic acid, for example oxalic, malonic, succmic, maleic, fumaric, phthalic or tefraphthalic; with hydroxycarboxylic acids, for example ascorbic, glycolic, lactic, malic, tartaric or citric acid; with aminoacids, for example aspartic or glutamic acid; with benzoic acid; or with organic sulfonic acids, such as (Cι-C₄)-alkyl- or aryl-sulfonic acids which are unsubstituted or substituted (for example, by a halogen) such as methane- or p-toluene sulfonic acid. Suitable hydroxides include inorganic hydroxides, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, aluminium hydroxide. Alcohols include alkanealcohols of 1-12 carbon atoms which may be unsubstituted or substituted, e.g. by a halogen).

ENANTIOMERS/TAUTOMERS

In all aspects of the present invention previously discussed, the invention includes, where appropriate all enantiomers and tautomers of the CDK4 modulators or candidate compounds ofthe invention. The man skilled in the art will recognise compounds that possess an optical properties (one or more chiral carbon atoms) or tautomeric characteristics. The conesponding enantiomers and/or tautomers may be isolated/prepared by methods known in the art.

STEREO AND GEOMETRIC ISOMERS

Some of the CDK4 modulators or candidate compounds of the invention may exist as stereoisomers and/or geometric isomers, e.g. they may possess one or more asymmetric and/or geometric centres and so may exist in two or more stereoisomeric and/or geometric forms. The present invention contemplates the use of all the individual stereoisomers and geometric isomers of those agents, and mixtures thereof. The terms used in the claims encompass these forms, provided said forms retain the appropriate functional activity (though not necessarily to the same degree).

The present invention also includes all suitable isotopic variations of the CDK4 modulators or candidate compounds, or pharmaceutically acceptable salts thereof. An isotopic variation of a CDK4 modulator or candidate compound of the present invention or a pharmaceutically acceptable salt thereof is defined as one in which at least one atom is replaced by an atom having the same atomic number but an atomic mass different from the atomic mass usually found in nature. Examples of isotopes that can be incorporated into the agent and pharmaceutically acceptable salts thereof include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulphur, fluorine and chlorine such as ²H, 1H, ¹³C, ¹⁴C, ¹⁵N, ¹⁷0, ¹⁸0, ³¹P, ³²P, ³⁵S, ¹⁸F and ³⁶C1, respectively. Certain isotopic variations of the agent and pharmaceutically acceptable salts thereof, for example, those in which a radioactive isotope such as ³H or ¹⁴C is incorporated, are useful in drug and/or substrate tissue distribution studies. Tritiated, i.e., ³H, and carbon-14, i.e., ¹⁴C, isotopes are particularly prefened for their ease of preparation and detectability. Further, substitution with isotopes such as deuterium, i.e., ²H, may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements and hence may be prefened in some circumstances. Isotopic variations of the CDK4 modulators or candidate compounds of the present invention can generally be prepared by conventional procedures using appropriate isotopic variations of suitable reagents.

SOLVATES

The present invention also includes solvate forms ofthe CDK4 modulators or candidate compounds. The terms used in the claims encompass these forms.

POLYMORPHS The invention furthermore relates to CDK4 modulators or candidate compounds of the present invention in their various crystalline forms, polymorphic forms and (an)hydrous forms. It is well established within the pharmaceutical industry that chemical compounds may be isolated in any of such forms by slightly varying the method of purification and or isolation form the solvents used in the synthetic preparation of such compounds.

PRODRUGS

The invention further includes CDK4 modulators or candidate compounds of the present invention in prodrag form. Such prodrugs are generally compounds of the invention wherein one or more appropriate groups have been modified such that the modification may be reversed upon ad iriistration to a human or mammalian subject. Such reversion is usually performed by an enzyme naturally present in such subject, though it is possible for a second agent to be admimstered together with such a prodrag in order to perform the reversion in vivo. Examples of such modifications include ester (for example, any of those described above), wherein the reversion may be carried out be an esterase etc. Other such systems will be well known to those skilled in the art.

THERAPEUTIC USE

The CDK4 modulators or candidate compounds of the present invention have been found to possess anti-proliferative activity and are therefore believed to be of use in the treatment of proliferative disorders, such as cancers, leukaemias or other disorders associated with uncontrolled cellular proliferation such as psoriasis and restenosis.

A further aspect ofthe invention therefore relates to a method of treating a proliferative disorder, said method comprising administering to a subject in need thereof a compound of formula [1], [2], [6]-[9], or a pharmaceutically acceptable salt thereof, in an amount sufficient to selectively inhibit CDK4 such that said proliferative disorder is treated.

Another aspect relates to a method of treating a proliferative disorder comprising selectively inhibiting CDK4 by administering to a subject in need thereof, a therapeutically effective amount of a compound of formula [1], [2], [6]-[9], or a pharmaceutically acceptable salt thereof, such that treatment of the proliferative disorder occurs. Another aspect ofthe invention relates to a method of preventing and/or treating a CDK4 related disorder comprising adrninistering a CDK4 modulator or candidate compound of the invention and/or a pharmaceutical composition according to the invention, wherein said CDK4 modulator, said candidate compound or said pharmaceutical, is capable of causing a beneficial preventative and/or therapeutic effect.

Preferably, for this aspect, the CDK modulator or candidate compound is selected from a compound of formula [1], [2], [6]-[9], or a pharmaceutically acceptable salt thereof.

A further aspect of the invention relates to the use of a CDK4 modulator or candidate compound according to the invention in the preparation of a medicament for treating a CDK4 related disorder. Preferably, the CDK4 related disorder is a proliferative disorder, more preferably cancer.

As used herein the phrase "preparation of a medicament" includes the use of the compound directly as the medicament in addition to its use in a screening programme for further therapeutic agents or in any stage ofthe manufacture of such a medicament.

Another aspect relates to a method of treating a CDK4 dependent disorder in a subject in need thereof, said method comprising administering to said subject a compound of formula [1], [2], [6]-[9], ^{or a} pharmaceutically acceptable salt thereof, in an amount sufficient to selectively inhibit CDK4.

Preferably, the CDK4 dependent disorder is a disorder associated with increased CDK4 activity. Even more preferably, the disorder is cancer.

The term "proliferative disorder" is used herein in a broad sense to include any disorder that requires control of the cell cycle, for example cardiovascular disorders such as restenosis and cardiomyopathy, auto-immune disorders such as glomerulonephritis and rheumatoid arthritis, dermatological disorders such as psoriasis, anti-inflammatory, anti-fungal, antiparasitic disorders such as malaria, emphysema and alopecia. In these disorders, the compounds of the present mvention may induce apoptosis or maintain stasis within the desired cells as required.

Preferably, the proliferative disorder is a cancer or leukaemia.

In another prefened embodiment, the proliferative disorder is psoriasis.

The compounds ofthe invention may inhibit any ofthe steps or stages in the cell cycle, for example, formation of the nuclear envelope, exit from the quiescent phase of the cell cycle (GO), Gl progression, chromosome decondensation, nuclear envelope breakdown, START, initiation of DNA replication, progression of DNA replication, termination of DNA replication, centrosome duplication, G2 progression, activation of mitotic or meiotic functions, chromosome condensation, centrosome separation, microtubule nucleation, spindle formation and function, interactions with microtubule motor proteins, chromatid separation and segregation, inactivation of mitotic functions, formation of contractile ring, and cytokinesis functions. In particular, the compounds of the invention may influence certain gene functions such as chromatin binding, formation of replication complexes, replication licensing, phosphorylation or other secondary modification activity, proteolytic degradation, microtubule binding, actin binding, septin binding, microtubule organising centre nucleation activity and binding to components of cell cycle signalling pathways.

As defined herein, an anti-proliferative effect within the scope ofthe present invention may be demonstrated by the ability to inhibit cell proliferation in an in vitro whole cell assay, for example using any of the cell lines A549, HeLa, HT-29, MCF7, Saos-2, CCRF-CEM, HL-60 and K-562, or by showing kinase inhibition in an appropriate assay. These assays, including methods for their performance, are described in more detail in the accompanying Examples. Using such assays it may be determined whether a compound is anti-proliferative in the context ofthe present invention.

In one prefened embodiment, the compound ofthe invention is administered orally. In one particularly prefened embodiment, the compounds of the invention are ATP- antagonistic inhibitors of CDK4.

Yet another aspect relates to a method of selectively inhibiting CDK4 in a cell comprising contacting said cell with an amount of a compound of formula [1], [2], [6]- [9] as defined above, or a pharmaceutically acceptable salt thereof, such that CDK4 is selectively inhibited in said cell.

Preferably, the cell is a cancer cell.

ADMINISTRATION

The pharmaceutical compositions of the present invention may be adapted for oral, rectal, vaginal, parenteral, intramuscular, intraperitoneal, intraarterial, intrathecal, intrabronchial, subcutaneous, intradermal, intravenous, nasal, buccal or sublingual routes of administration.

For oral administration, particular use is made of compressed tablets, pills, tablets, gellules, drops, and capsules. Preferably, these compositions contain from 1 to 250 mg and more preferably from 10-100 mg, of active ingredient per dose.

Other forms of administration comprise solutions or emulsions which may be injected intravenously, intraarterially, intrathecally, subcutaneously, intradermally, intraperitoneally or intramuscularly, and which are prepared from sterile or sterilisable solutions. The pharmaceutical compositions of the present invention may also be in form of suppositories, pessaries, suspensions, emulsions, lotions, ointments, creams, gels, sprays, solutions or dusting powders.

An alternative means of transdermal administration is by use of a skin patch. For example, the active ingredient can be incorporated into a cream consisting of an aqueous emulsion of polyethylene glycols or liquid paraffin. The active ingredient can also be incoφorated, at a concentration of between 1 and 10% by weight, into an ointment consisting of a white wax or white soft paraffin base together with such stabilisers and preservatives as may be required.

Injectable forms may contain between 10 - 1000 mg, preferably between 10 - 250 mg, of active ingredient per dose.

Compositions may be formulated in unit dosage form, i.e., in the fonn of discrete portions containing a unit dose, or a multiple or sub-unit of a unit dose.

DOSAGE

A person of ordinary skill in the art can easily determine an appropriate dose of one of the instant compositions to administer to a subject without undue experimentation. Typically, a physician will determine the actual dosage which will be most suitable for an individual patient and it will depend on a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drag combination, the severity of the particular condition, and the individual undergoing therapy. The dosages disclosed herein are exemplary of the average case. There can of course be individual instances where higher or lower dosage ranges are merited, and such are within the scope of this invention.

Depending upon the need, the agent may be administered at a dose of from 0.01 to 30 mg/kg body weight, such as from 0.1 to 10 mg/kg, more preferably from 0.1 to 1 mg/kg body weight.

In an exemplary embodiment, one or more doses of 10 to 150 mg/day will be administered to the patient for the treatment of malignancy.

CDK4 FRAGMENT

Another aspect ofthe invention relates to a fragment of CDK4, or a homologue, mutant, or derivative thereof, comprising a ligand binding domain, said ligand binding domain being defined by the amino acid residue structural coordinates selected from one or more ofthe following: V20, F93,D99, L147, E144 and DI 58.

As used herein, the term "ligand binding domain (LBD)" means the ligand binding region of CDK4 which is responsible for ligand binding. The term "ligand binding domain" also includes a homologue ofthe hgand binding domain, or a portion thereof.

As used herein, the term "portion thereof means the stractural co-ordinates conesponding to a sufficient number of amino acid residues of the CDK4 sequence (or homologue thereof) that are capable of interacting with a candidate compound capable of binding to the LBD. This term includes ligand binding domain amino acid residues having amino acid residues from about 4A to about 5A of a bound compound or fragment thereof. Thus, for example, the structural co-ordinates provided in the homology model may contain a subset of the amino acid residues in the LBD which may be useful in the modelling and design of compounds that bind to the LBD.

In one prefened embodiment, the fragment of CDK4, or a homologue, mutant or derivative thereof, conesponds to a portion ofthe structure co-ordinates of Table 1.

Another aspect of the invention relates to the use of the above-described fragment of CDK4, or a homologue, mutant, or derivative thereof, in an assay for identifying candidate compounds capable of modulating CDK4.

The CDK4 proteins produced by a host recombinant cell may be secreted or may be contained intracellularly depending on the nucleotide sequence and/or the vector used.

As will be understood by those skilled in the art, expression vectors containing a CDK4 encoding nucleotide sequence or a mutant, variant, homologue, derivative or fragment thereof, may be designed with signal sequences which direct secretion of the CDK4 coding sequences through a particular prokaryotic or eukaryotic cell membrane. The CDK4 encoding sequence may be fused (eg. ligated) to nucleotide sequences encoding a polypeptide domain which will facilitate purification of soluble proteins (Kroll

DJ et al (1993) DNA Cell Biol 12:441-53). Preferably, the polypeptide domain which facilitates purification of soluble proteins is fused in frame with the CDK4 encoding sequence. Such purification facilitating domains include, but are not limited to, metal chelating peptides - such as histidine-tryptophan modules that allow purification on immobilised metals (Porath J (1992) Protein Expr Purif 3, 263-281), protein A domains that allow purification on immobilised immunoglobulin, and the domain utilised in the

FLAGS extension/affinity purification system (hnmunex Corp, Seattle, WA). The inclusion of a cleavable linker sequence such as Factor XA or enterokinase (Invitrogen,

San Diego, CA) between the purification domain and CDK4 is useful to facilitate purification.

NUCLEOTIDE SEQUENCES As used herein, the term "nucleotide sequence" refers to nucleotide sequences, oligonucleotide sequences, polynucleotide sequences and variants, homologues, fragments and derivatives thereof (such as portions thereof) which comprise the nucleotide sequences encoding CDK4.

The nucleotide sequence may be DNA or RNA of genomic or synthetic or recombinant origin, which may be double-stranded or single-stranded whether representing the sense or antisense strand or combinations thereof.

Preferably, the term nucleotide sequence is prepared by use of recombinant DNA techniques (e.g. recombinant DNA). The nucleotide sequences may include within them synthetic or modified nucleotides. A number of different types of modification to oligonucleotides are known in the art. These include methylphosphonate and phosphorothioate backbones, addition of acridine or polylysine chains at the 3' and/or 5' ends of the molecule. For the purposes of the present invention, it is to be understood that the nucleotide sequences described herein may be modified by any method available in the art. It will be understood by a skilled person that numerous different nucleotide sequences can encode the same protein as a result of the degeneracy of the genetic code. In addition, it is to be understood that skilled persons may, using routine techniques, make nucleotide substitutions that do not substantiaUy affect the activity encoded by the nucleotide sequence of the present invention to reflect the codon usage of any particular host organism in which the target is to be expressed. Thus, the terms "variant",

"homologue" or "derivative" in relation to nucleotide sequences include any substitution of, variation of, modification of, replacement of, deletion of or addition of one (or more) nucleic acids from or to the sequence providing the resultant nucleotide sequence encodes a functional protein according to the present invention (or even a modulator of CDK4 according to the present invention if said modulator comprises a nucleotide sequence or an amino acid sequence).

AMINO ACID SEQUENCES As used herein, the term "amino acid sequence" is synonymous with the term "polypeptide" and/or the term "protein". In some instances, the term "amino acid sequence" is synonymous with the term "peptide".

The amino acid sequence may be isolated from a suitable source, or it may be made synthetically or it may be prepared by use of recombinant DNA techniques.

VARIANTS/HOMOLOGUES/DERIVATIVES/FRAGMENTS

The CDK4 described herein is intended to include any polypeptide, which has the activity of the naturally occurring CDK4 and includes all vertebrate and mammalian forms. Such terms also include polypeptides that differ from naturally occurring forms of CDK4 by having amino acid deletions, substitutions, and additions, but which retain the activity of CDK4.

The term "variant" is used to mean a naturally occurring polypeptide or nucleotide sequences which differs from a wild-type or a native sequence. The term "fragment" indicates that a polypeptide or nucleotide sequence comprises a fraction of a wild-type or a native sequence. It may comprise one or more large contiguous sections of sequence or a plurality of small sections. The sequence may also comprise other elements of sequence, for example, it maybe a fusion protein with another protein. Preferably the sequence comprises at least 50%, more preferably at least 65%, more preferably at least 80%, most preferably at least 90% ofthe wild-type sequence.

The present invention also encompasses the use of variants, homologues and derivatives of nucleotide and amino acid sequences. Here, the term "homologue" means an entity having a certain homology with amino acid sequences or nucleotide sequences. Here, the term "homology" can be equated with "identity".

In the present context, an homologous sequence is taken to include an amino acid sequence which may be at least 75, 85 or 90% identical, preferably at least 95 or 98% identical to the subject sequence. Although homology can also be considered in terms of similarity (i.e. amino acid residues having similar chemical properties/functions), it is prefened to express homology in terms of sequence identity.

An homologous sequence is taken to include a nucleotide sequence which may be at least 75, 85 or 90% identical, preferably at least 95 or 98% identical to the subject sequence.

Homology comparisons can be conducted by eye, or more usually, with the aid of readily available sequence comparison programs. These commercially available computer programs can calculate % homology between two or more sequences.

% homology may be calculated over contiguous sequences, i.e. one sequence is aligned with the other sequence and each amino acid in one sequence is directly compared with the conesponding amino acid in the other sequence, one residue at a time. This is called an "ungapped" alignment. Typically, such ungapped alignments are performed only over a relatively short number of residues. Although this is a very simple and consistent method, it fails to take into consideration that, for example, in an otherwise identical pair of sequences, one insertion or deletion will cause the following amino acid residues to be put out of alignment, thus potentially resulting in a large reduction in % homology when a global alignment is performed. Consequently, most sequence comparison methods are designed to produce optimal alignments that take into consideration possible insertions and deletions without penalising unduly the overall homology score. This is achieved by inserting "gaps" in the sequence alignment to try to maximise local homology.

However, these more complex methods assign "gap penalties" to each gap that occurs in the alignment so that, for the same number of identical amino acids, a sequence alignment with as few gaps as possible - reflecting higher relatedness between the two compared sequences - will achieve a liigher score than one with many gaps. "Affine gap costs" are typically used that charge a relatively high cost for the existence of a gap and a smaller penalty for each subsequent residue in the gap. This is the most commonly used gap scoring system. High gap penalties will of course produce optimised alignments with fewer gaps. Most alignment programs allow^r the gap penalties to be modified. However, it is prefened to use the default values when using such software for sequence comparisons. For example when using the GCG Wisconsin Bestfit package the default gap penalty for amino acid sequences is -12 for a gap and -4 for each extension.

Calculation of maximum % homology therefore firstly requires the production of an optimal alignment, taking into consideration gap penalties. A suitable computer program for canying out such an alignment is the GCG Wisconsin Bestfit package (University of Wisconsin, U.S.A.; Devereux et al., 1984, Nucleic Acids Research 12:387). Examples of other software than can perform sequence comparisons include, but are not limited to, the BLAST package (see Ausubel et al, 1999 ibid - Chapter 18), FASTA (Atschul et al, 1990, J. Mol. Biol., 403-410) and the GENEWORKS suite of comparison tools. Both BLAST and FASTA are available for offline and online searching (see Ausubel et al, 1999 ibid, pages 7-58 to 7-60). However, for some applications, it is prefened to use the GCG Bestfit program. A new tool, called BLAST 2 Sequences is also available for comparing protein and nucleotide sequence (see

FEMS Microbiol Lett 1999 174(2): 247-50; FEMS Microbiol Lett 1999 177(1): 187-8)

Although the final % homology can be measured in terms of identity, the alignment process itself is typically not based on an all-or-nothing pair comparison. Instead, a scaled similarity score matrix is generally used that assigns scores to each pairwise comparison based on chemical similarity or evolutionary distance. An example of such a matrix commonly used is the BLOSUM62 matrix - the default matrix for the BLAST suite of programs. GCG Wisconsin programs generally use either the public default values or a custom symbol comparison table if supplied (see user manual for further details). For some applications, it is prefened to use the public default values for the GCG package, or in the case of other software, the default matrix, such as BLOSUM62. Once the software has produced an optimal alignment, it is possible to calculate % homology, preferably % sequence identity. The software typically does this as part of the sequence comparison and generates a numerical result.

The sequences may also have deletions, insertions or substitutions of amino acid residues, which produce a silent change and result in a functionally equivalent substance. Deliberate amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophihcity, and/or the amphipathic nature of the residues as long as the secondary binding activity of the substance is retained. For example, negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; and amino acids with uncharged polar head groups having similar hydrophihcity values include leucine, isoleucine, valine, glycine, alanine, asparagine, glutamine, serine, threonine, phenylalanine, and tyrosine.

Conservative substitutions may be made, for example according to the Table below. Amino acids in the same block in the second column and preferably in the same line in the third column may be substituted for each other:

Homologous substitution (substitution and replacement are both used herein to mean the interchange of an existing amino acid residue, with an alternative residue) may occur i.e. like-for-like substitution such as basic for basic, acidic for acidic, polar for polar etc. Non-homologous substitution may also occur i.e. from one class of residue to another or alternatively involving the inclusion of unnatural amino acids such as ornithine (hereinafter refened to as Z), diaminobutyric acid omithine (hereinafter refened to as B), norleucine ornithine (hereinafter refened to as O), pyriylalanine, thienylalanine, naphthylalanine and phenylglycine.

Replacements may also be made by unnatural amino acids include; alpha* and alpha- disubstituted* amino acids, N-alkyl amino acids*, lactic acid*, halide derivatives of natural amino acids such as trifluorotyrosine*, p-Cl-phenylalanine*, p-Br-phenylalaiiine*, p-I-phenylalanine*, L-allyl-glycine*, β-alanine*, L-α-amino butyric acid*, L-γ-amino butyric acid*, L-α-amino isobutyric acid*, L-ε-amino caproic acid , 7-amino heptanoic acid*, L-methionine sulfone*^*, L-norleucine*, L-norvaline*, p-nitro-L-phenylalanine*, L- hydroxyproline , L-fhioproline*, methyl derivatives of phenylalanine (Phe) such as 4- methyl-Phe*, pentamethyl-Phe*, L-Phe (4-amino) , L-Tyr (methyl)*, L-Phe (4- isopropyl)*, L-Tic (l,2,3,4-tetrahydroisoquinoline-3-carboxyl acid)*, L-diaminopropionic acid ^# and L-Phe (4-benzyl)*. The notation * has been utilised for the purpose of the discussion above (relating to homologous or non-homologous substitution), to indicate the hydrophobic nature of the derivative whereas # has been utilised to indicate the hydrophilic nature ofthe derivative, #* indicates amphipathic characteristics. The term "derivative" or "derivatised" as used herein includes chemical modification of an entity, such as candidate compound or a CDK4modulator. Illustrative of such chemical modifications would be replacement of hydrogen by a halo group, an alkyl group, an acyl group or an a ino group.

Variant amino acid sequences may include suitable spacer groups that may be inserted between any two amino acid residues of the sequence including alkyl groups such as methyl, ethyl or propyl groups in addition to amino acid spacers such as glycine or β- alanine residues. A further form of variation, involves the presence of one or more amino acid residues in peptoid form, will be well understood by those skilled in the art. For the avoidance of doubt, "the peptoid form" is used to refer to variant amino acid residues wherein the α-carbon substituent group is on the residue's nitrogen atom rather than the α-carbon. Processes for preparing peptides in the peptoid form are known in the art, for example Simon RJ et al., PNAS (1992) 89(20), 9367-9371 and Horwell DC, Trends Biotechnol. (1995) 13(4), 132-134.

MUTANT

As used herein, the term "mutant" refers to CDK4 comprising one or more changes in the wild-type CDK4 sequence.

The term "mutant" is not limited to amino acid substitutions ofthe amino acid residues in CDK4, but also includes deletions or insertions of nucleotides which may result in changes in the amino acid residues in the amino acid sequence of CDK4.

The present invention also enables the solving of the crystal stmcture of CDK4 mutants. More particularly, by virtue of the present invention, the location of the active site of CDK4 based on the stractural coordinates of Table 1 permits the identification of desirable sites for mutation. For example, one or more mutations may be directed to a particular site - such as the active site - or combination of sites of CDK4. Similarly, only a location on, at or near the enzyme surface may be replaced, resulting in an altered surface charge of one or more charge units, as compared to the wild-type enzyme. Alternatively, an amino acid residue in CDK4 may be chosen for replacement based on its hydrophilic or hydrophobic characteristics.

Such mutants may be characterised by any one of several different properties as compared with wild-type CDK4. For example, such mutants may have altered surface charge of one or more charge units, or have an increased stability to subunit dissociation, or an altered substrate specificity in comparison with, or a higher specific activity than, wild-type CDK4.

The mutants may be prepared in a number of ways that are known by a person skilled in the art. For example, mutations may be introduced by means of oligonucleotide- directed mutagenesis or other conventional methods. Alternatively, mutants of CDK4 may be generated by site specific replacement of a particular amino acid with an unnaturally occurring amino acid. This may be achieved by growing a host organism capable of expressing either the wild-type or mutant polypeptide on a growth medium depleted of one or more natural amino acids but enriched in one or more conesponding unnaturally occurring amino acids.

HOST CELLS As used herein, the term "host cell" refers to any cell that comprises nucleotide sequences that are of use in the present invention, for example, nucleotide sequences encoding CDK4.

Host cells may be transformed or transfected with a nucleotide sequence contained in a vector e.g. a cloning vector. Preferably, said nucleotide sequence is carried in a vector for the replication and/or expression of the nucleotide sequence. The cells will he chosen to be compatible with the said vector and may for example be prokaryotic (for example bacterial), fungal, yeast or plant cells.

The gram-negative bacterium E. coli is widely used as a host for cloning nucleotide sequences. This organism is also widely used for heterologous nucleotide sequence expression. However, large amounts of heterologous protein tend to accumulate inside the cell. Subsequent purification of the desired protein from the bulk of E. coli intracellular proteins can sometimes be difficult.

In contrast to E. coli, bacteria from the genus Bacillus are very suitable as heterologous hosts because of their capability to secrete proteins into the culture medium. Other bacteria suitable as hosts are those from the genera Streptomyces and Pseudomonas.

Depending on the nature of the polynucleotide and/or the desirability for further processing of the expressed protein, eukaryotic hosts including yeasts or other fungi may be prefened. In general, yeast cells are prefened over fungal cells because yeast cells are easier to manipulate. However, some proteins are either poorly secreted from the yeast cell, or in some cases are not processed properly (e.g. hyperglycosylation in yeast). In these instances, a different fungal host organism should be selected.

Examples of expression hosts are fungi - such as Aspergillus species (such as those described in EP-A-0184438 and EP-A-0284603) and Trichoderma species; bacteria - such as Bacillus species (such as those described in EP-A-0134048 and EP-A- 0253455), Streptomyces species and Pseudomonas species; yeasts - such as Kluyveromyces species (such as those described in EP-A-0096430 and EP-A-0301670) and Saccharomyces species; and mammalian cells - such as CHO-K1 cells.

The use of host cells may provide for post-translational modifications as may be needed to confer optimal biological activity on recombinant expression products ofthe present invention.

Aspects of the present invention also relate to host cells comprising the CDK4 constructs of the present invention. The CDK4 constructs may comprise a nucleotide sequence for replication and expression ofthe sequence. The cells will be chosen to be compatible with the vector and may for example be prokaryotic (for example bacterial), fungal, yeast or plant cells.

In a prefened embodiment, the host cells are mammalian cells, such as CHO-K1 cells. VECTOR

Aspects of the present invention relate to a vector comprising a nucleotide sequence, such as a nucleotide sequence encoding CDK4 or a modulator of CDK4, administered to a subject.

Preferably, CDK4 or the modulator of CDK4 is prepared and/or delivered using a genetic vector.

As it is well known in the art, a vector is a tool that allows or facilitates the transfer of an entity from one environment to another. In accordance with the present invention, and by way of example, some vectors used in recombinant DNA techniques allow entities, such as a segment of DNA (such as a heterologous DNA segment, such as a heterologous cDNA segment), to be transfened into a host and/or a target cell for the purpose of replicating the vectors comprising nucleotide sequences and/or expressing the proteins encoded by the nucleotide sequences. Examples of vectors used in recombinant DNA techniques include, but are not limited to, plasmids, chromosomes, artificial chromosomes or viruses.

The term "vector" includes expression vectors and/or transformation vectors.

The term "expression vector" means a construct capable of in vivo or in vitro/ex vivo expression.

The term "transformation vector" means a construct capable of being transfened from one species to another.

REGULATORY SEQUENCES

In some applications, nucleotide sequences are operably linked to a regulatory sequence which is capable of providing for the expression ofthe nucleotide sequence, such as by a chosen host cell. By way of example, a vector comprising the CDK4 nucleotide sequence is operably linked to such a regulatory sequence i.e. the vector is an expression vector. The term "operably linked" refers to a juxtaposition wherein the components described are in a relationship permitting them to fiinction in their intended manner. A regulatory sequence "operably linked" to a coding sequence is ligated in such a way that expression of the coding sequence is achieved under conditions compatible with the control sequences.

The term "regulatory sequences" includes promoters and enhancers and other expression regulation signals.

The term "promoter" is used in the normal sense of the art, e.g. an RNA polymerase binding site.

Enhanced expression of a nucleotide sequence, for example, a nucleotide sequence encoding CDK4, may also be achieved by the selection of heterologous regulatory regions, e.g. promoter, secretion leader and terminator regions, which serve to increase expression and, if desired, secretion levels of the protein of interest from the chosen expression host and or to provide for the inducible control of the expression of CDK4. In eukaryotes, polyadenylation sequences may be operably connected to the CDK4 nucleotide sequence.

Preferably, the CDK4 nucleotide sequence is operably linked to at least a promoter.

Aside from the promoter native to the gene encoding the CDK4 nucleotide sequence, other promoters may be used to direct expression of the CDK4 polypeptide. The promoter may be selected for its efficiency in directing the expression of the CDK4 nucleotide sequence in the desired expression host.

In another embodiment, a constitutive promoter may be selected to direct the expression of the CDK4 nucleotide sequence. Such an expression constract may provide additional advantages since it circumvents the need to culture the expression hosts on a medium containing an inducing substrate. Hybrid promoters may also be used to improve inducible regulation of the expression constract.

The promoter can additionally include features to ensure or to increase expression in a suitable host. For example, the features can be conserved regions such as a Pribnow Box or a TATA box. The promoter may even contain other sequences to affect (such as to maintain, enhance, decrease) the levels of expression of the CDK4nucleotide sequence. For example, suitable other sequences include the Shl-intron or an ADH intron. Other sequences include inducible elements - such as temperature, chemical, light or stress inducible elements. Also, suitable elements to enhance transcription or translation may be present.

EXPRESSION VECTOR

Preferably, nucleotide sequences, such as nucleotide sequences encoding CDK4 or modulators of CDK4, are inserted into a vector that is operably linked to a control sequence that is capable of providing for the expression of the coding sequence by the host cell.

Nucleotide sequences produced by a host recombinant cell may be secreted or may be contained intracellularly depending on the sequence and/or the vector used. As will be understood by those of skill in the art, expression vectors can be designed with signal sequences, which direct secretion of the nucleotide sequence through a particular prokaryotic or eukaryotic cell membrane.

Preferably, the expression vectors are stably expressed in CHO cells as described previously (Ehlers et al. (1996) Biochemistry 35, 9549-9559). More preferably, the expression vectors are pLEN- tACEΔ36g(l, 2, 3, 4) and pLEN- tACEΔ36g(l,3).

FUSION PROTEINS CDK4 or a modulator of CDK4 may be expressed as a fusion protein to aid extraction and purification and or delivery of the modulator of CDK4 or the CDK4 protein to an individual and/or to facilitate the development of a screen for modulators of CDK4. Examples of fusion protein partners include glutathione-S-transferase (GST), 6xHis,

GAL4 (DNA binding and/or transcriptional activation domains) and β-galactosidase.

It may also be convenient to include a proteolytic cleavage site between the fusion protein partner and the protein sequence of interest to allow removal of fusion protein sequences. Preferably, the fusion protein will not hinder the activity of the protein of interest.

The fusion protein may comprise an antigen or an antigenic determinant fused to the substance of the present invention. In this embodiment, the fusion protein may be a non-naturally occurring fusion protein comprising a substance, which may act as an adjuvant in the sense of providing a generalised stimulation of the immune system. The antigen or antigenic determinant may be attached to either the amino or carboxy terminus ofthe substance.

ORGANISM

The term "organism" in relation to the present invention includes any organism that could comprise CDK4 and or modulators of CDK4. Examples of organisms may include mammals, fungi, yeast or plants.

Preferably, the organism is a mammal. More preferably, the organism is a human.

TRANSFORMATION

As indicated earlier, the host organism can be a prokaryotic or a eukaryotic organism. Examples of suitable prokaryotic hosts include E. coli and Bacillus subtilis. Teachings on the transformation of prokaryotic hosts are well documented in the art, for example see Sambrook et al (Molecular Cloning: A Laboratory Manual, 2nd edition, 1989, Cold Spring Harbor Laboratory Press) and Ausubel et al, Cunent Protocols in Molecular Biology (1995), John Wiley & Sons, Inc. Examples of suitable eukaryotic hosts include mammalian cells. If a prokaryotic host is used then the nucleotide sequence, such as the CDK4 nucleotide sequence, may need to be suitably modified before transformation - such as by removal of introns.

Thus, the present invention also relates to the transformation of a host cell with a nucleotide sequence, such as CDK4 or a modulator of CDK4. Host cells transformed with the nucleotide sequence may be cultured under conditions suitable for the expression and recovery ofthe encoded protein from cell culture. The protein produced by a recombinant cell may be secreted or may be contained intracellularly depending on the sequence and/or the vector used. As will be understood by those of skill in the art, expression vectors containing coding sequences can be designed with signal sequences which direct secretion of the coding sequences through a particular prokaryotic or eukaryotic cell membrane. Other recombinant constructions may join the coding sequence to nucleotide sequence encoding a polypeptide domain, which will facilitate purification of soluble proteins (Kroll DJ et al (1993) DNA Cell Biol 12:441- 53) e.g. 6-His or Glutathione-S-transferase.

TRANSFECTION

Vectors comprising for example, the CDK4 nucleotide sequence, may be introduced into host cells, for example, mammalian cells, using a variety of methods.

Typical transfection methods include electroporation, DNA biolistics, lipid-mediated transfection, compacted DNA-mediated transfection, liposomes, immunoliposomes, lipofectin, cationic agent-mediated, cationic facial amphiphiles (CFAs) (Nature Biotech. (1996) 14, 556), multivalent cations such as spermine, cationic lipids or polylysine, 1, 2,-bis (oleoylQxy)-3-(trimethylammonio) propane (DOTAP)-cholesterol complexes (Wolff and Trabetskoy 1998 Nature Biotechnology 16: 421) and combinations thereof.

Uptake of nucleic acid constructs by mammalian cells is enhanced by several known transfection techniques for example those including the use of transfection agents. Example of these agents include cationic agents (for example calcium phosphate and DEAE-dextran) and lipofectants (for example lipofectam™ and transfectam™).

Typically, nucleic acid constructs are mixed with the transfection agent to produce a composition.

Such methods are described in many standard laboratory manuals - such as Sambrook et al, Molecular Cloning: A Laboratory Manual, 2d ed. (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.

The present invention is further described by way of example, and with reference to the following figures wherein:

Figure 1 shows the homology stracture generated for CDK2 based on sequence comparisons with the X-ray structures of CDK2 and CDK6.

Figure 2 shows a comparison of the relative positions of inhibitors [5] and [6] in the ATP binding sites of CDK2 and CDK4. For CDK2, the X-ray stracture of [5] in complex with CDK2/cyclin A was used, while for [6], the bound structure was predicted by docking with CDK4.

Figure 3 shows the predicted binding mode ofthe highly CDK4 selective inhibitor, [9]. Interactions with Asp99 and Glu 144 in addition to the H-bond contacts are labelled.

EXAMPLES

General Methods

The methods described here may employ, unless otherwise indicated, conventional techniques of chemistry, molecular biology, microbiology, recombinant DNA and immunology, which are within the capabilities of a person of ordinary skill in the art. Such techniques are explained in the literature. See, for example, J. Sambrook, E. F. Fritsch, and T. Maniatis, 1989, Molecular Cloning: A Laboratory Manual, Second Edition, Books 1-3, Cold Spring Harbor Laboratory Press; Ausubel, F. M. et al. (1995 and periodic supplements; Current Protocols in Molecular Biology, ch. 9, 13, and 16, John Wiley & Sons, New York, N.Y.); B. Roe, J. Crabtree, and A. Kahn, 1996, DNA

Isolation and Sequencing: Essential Techniques, John Wiley & Sons; J. M. Polak and

James O'D. McGee, 1990, In Situ Hybridization: Principles and Practice; Oxford

University Press; M. J. Gait (Editor), 1984, Oligonucleotide Synthesis: A Practical Approach, Irl Press; D. M. J. Lilley and J. E. Dahlberg, 1992, Methods ofEnzymology:

DNA Structure Part A: Synthesis and Physical Analysis of DNA Methods in

Enzymology, Academic Press; Using Antibodies : A Laboratory Manual : Portable

Protocol NO. I by Edward Harlow, David Lane, Ed Harlow (1999, Cold Spring Harbor

Laboratory Press, ISBN 0-87969-544-7); Antibodies : A Laboratory Manual by Ed Harlow (Editor), David Lane (Editor) (1988, Cold Spring Harbor Laboratory Press, ISBN 0-87969-314-2), 1855. Handbook of Drag Screening, edited by Ramakrishna Seethala, Prabhavathi B. Fernandes (2001, New York, NY, Marcel Dekker, ISBN 0- 8247-0562-9); and Lab Ref: A Handbook of Recipes, Reagents, and Other Reference Tools for Use at the Bench, Edited Jane Roskams and Linda Rodgers, 2002, Cold Spring Harbor Laboratory, ISBN 0-87969-630-3. Each of these general texts is herein incoφorated by reference.

METHODS AND MATERIALS

Homology Model Construction

The homology model for CDK4 was generated using the program module Homology within the molecular modelling package Insightll (Accelrys, San Diego, CA). For the model construction, the CDK2 and CDK6 structures were used. Sequence alignment of CDK4 with CDK2 was performed using the PAM 120 multiple scoring matrix with a dimension block of 0.6, a high significance p value of 0.0001, a not significant p value of 0.1 and a pairwise threshold of 60. Using a combination of the two structures to generate coordinates for the regions that had the highest identity in each kinase, a model structure for the kinase domain was constructed. The strategy generally involved using CDK2 to define the structurally conserved regions (SCR's) from which the coordinates were subsequently transfened. This was then followed by loop construction where the non-SCR's were generated from CDK2 and CDK6 and additionally by de-novo building and subsequent evaluation of the most realistic coordinates (in terms of energetics ofthe loop itself and the exclusion of loops leading to overlapping atoms). After loop building was completed for missing coordinates, the raw coordinates were then refined using successive rounds of end repair, splice repairing using an omega force constant of 50, energy minimization (100 steps of steepest descent to a derivative of 5). The model was then completed through using a further mimmisation and 1 ps of molecular dynamics to more fully explore the conformational space of the loop regions. The final model stracture was then checked against databases of protein structures for bond length and dihedral angle violations.

The results indicated that these as a whole were within acceptable limits with >80% of residues having phi-psi plots with the allowed region in Ramachandran space.

Molecular modelling

The stracture coordinates of the ternary complex of CDK2/cyclin A/p27^!αpι were obtained from the RCSB (accession code 1 JSU). CDK inhibitors were then docked into the ATP site of the CDK2 X-ray crystal stracture or the CDK4 model structure using the Affinity program (Molecular Simulations, San Diego, CA). The binding site was defined as an 8 A radius from the centre of a ligand binding mode. This molecular docking routine, which incoφorates a full molecular mechanics approach, allows for flexibility both in the ligand and in the side chains and backbone of the receptor (the positions of the alpha carbon atoms were fixed during the simulation). The calculation was performed using the CVFF force field in a two-step process using an implicitly derived solvation model and geometric H-bond restraints. For the initial phase of the calculation, the peptide was minimised into the groove using a simple non-bonded method where the Coulombic and Van der Waals terms are scaled to zero and 0.1, respectively. The subsequent refinement phase involved conformational sampling using molecular dynamics calculated over 5 ps in 100 fs stages, where the temperature was scaled from 500 K to 300 K. The calculation was completed by a final minimisation over 1,000 steps using the Polak-Ribiere Conjugate Gradient method.

pKa calculation pK_a values of the ionisable nitrogens for the CDK inhibitors were calculated using the ACD Labs (Toronto, Canada) pK_a DB software. ACD pK_a DB is a program that calculates accurate acid-base ionization constants (pK_a values) at 25°C and zero ionic strength in aqueous solutions and is reported to have a general accuracy of ± 0.2 pK_a units.

Synthesis of Compounds [1H91

Typical procedure for preparation of 3-dimethylamino-l-(thiazol-5-yl)propenone A solution of 3-chloropentane-2,4-dione (2.5 g, 19 mmol) in MeOH (10 mL) was treated with methyl thiourea (1.67g, 19 mmol) and pyridine (1.5 mL). The mixture was stined at room temperature for 2 h. Precipitated l-(4-methyl-2-methylaminothiazol-5- yl)ethanone (2.10 g, 65 %) was filtered, washed with Et₂O, and dried. Mp 201-203 °C. Anal. RP-HPLC (Vydac 218TP54 250 x 4.6 mm column; linear gradient elution using H₂O/MeCN containing 0.1 % CF₃COOH): t_R 5.5 min (10-70 % MeCN, purity 100 %). 1H-NMR (500 MHz, CDC1₃): 2.47 (s, 3H, CH₃), 2.61 (s, 3H, CH₃), 3.18 (s, 3H, CH₃). ¹³C-NMR (DMSO-d₆): δ 19.16, 30.05, 31.54, 49.28, 121.78, 158.54, 188.81. MS (EST) m/z 170.87 (C₇H₁₀N₂OS requires 170.23). This material (2.05 g, 12 mmol) was suspended in NN-dimethylformamide dimethylacetal (5.3 mL, 4.80 g, 40 mmol) and the mixture was heated at 120 °C with stirring for 16 h. After cooling the reaction mixture was evaporated to dryness. The residue was crystallised from EtOAc to afford 3-dimethylamino-l-(4-methyl-2-methylaminothiazol-5-yl)propenone as an orange solid (1.82 g, 67 %): mp 209-211 °C. Anal. RP-HPLC: t_R 7.1 min (10-70 % MeCΝ, purity 100 %). 1H-ΝMR (CDC1₃): £2.55 (s, 3H, CH₃), 2.94 (s, 3H, CH₃), 3.41 (s, 6H, CH₃), 5.30 (d, IH, J= 12.2 Hz, CH), 7.64 (d, IH, J= 12.2 Hz, CH). ¹³C-NMR (DMSO-d₆): δ 18.94, 31.41, 54.99, 94.32, 122.05, 152.96, 153.83, 169.41, 179.89. MS (ESf) m/z 226.11 (M+H]). Anal. (C₁₀Hι₅N₃OS.MeOH) C, H, N.

3-Dimethylamino-l-(2-ethylamino-4-methylthiazol-5-yl)propenone Mp 204-205 °C. Anal. RP-HPLC: t_R 7.3 min (10-70 % MeCN, purity 100 %). 1H- NMR (CDC1₃): δ 1.25 (t, 3H, J= 6.0 Hz, CH₃), 2.49 (s, 3H, CH₃), 3.20 (s, 6H, CH₃), 3.28 (m, 2H, CH₂), 5.35 (d, IH, J= 11.5 Hz, CH), 7.67 (d, IH, J= 11.5 Hz, CH). ¹³C- NMR (DMSO-</₆): £ 14.92, 18.95, 31.41, 54.99, 94.34, 121.81, 152.92, 153.74, 168.49, 179.90. MS (ESf) m/z 240.17 (M+H)⁺(C_πH₁₇N₃OS requires 239.34). 3-Dimethylamino-l-(2,4-dimethylthiazol-5-yl)propenone

Mp 96-98 °C. Anal. RP-HPLC: t_R 7.1 min (10-70 % MeCN, purity 100 %). 1H-NMR

(CDC1₃): £2.66 (s, 6H, CH₃), 2.70 (s, 6H, CH₃), 5.37 (d, IH, J= 12.2 Hz, CH), 7.66 (d,

IH, J = 12.2 Hz, CH). ¹³C-NMR (DMSO-d₆): £ 18.19, 19.52, 37.77, 45.19, 94.50, 134.01, 153.62, 154.38, 165.64, 179.93. MS (ESI^1") m/z 211.01 (M+H)⁺. Anal.

(C₁₀H₁₄N₂OS) C, H, N.

General procedure for paration of N-phenyl-guanidine nitrates

To an ice-cooled mixture of the appropriate aniline (25 mmol) in EtOH (6 mL) nitric acid (1.8 mL of 70 % solution in H O) was added drop-wise with stirring. After complete addition, cyanamide (5 mL of 50 % solution in H₂O) was added and the mixture was heated at 100 °C for 16-18 h under N₂. After cooling to room temperature, it was poured into excess Et₂O and was basified with aq NaOH solution. The ethereal layer was separated and the aqueous phase was extracted with Et O several times. The combined organic phases were washed with brine, dried on MgSO₄, filtered and evaporated. The resulting residue was purified by crystallisation or flash chromatography in appropriate mixtures of EtOAc/PE or EtOAc/MeOH.

General procedure for preparation of [4-(thiazol-5-yl pyrimidin-2-yllphenylamines A mixture of 3-dimethylamino-l-(thiazol-5-yl)propenone (1 equiv), the appropriate N- phenyl-guanidine nitrate (2 equiv) and NaOH (1 equiv) in 2-methoxyethanol was heated at 125 °C for 22 h under N . After cooling the solvent was evaporated and the residue was purified by flash chromatography using appropriate mixtures of EtOAc/hexane as the eluant. Pure products were obtained following recrystallisation.

(3-Aminomethyl-phenyl)-[4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl]- amine [1]

By treatment of N- {3-[4-(4-methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-ylamino]- benzyl} -acetamide with HCl MeOH. Yellow solid. Mp 287-289 °C. Anal. RP-HPLC: t_R = 10.1 min (0 - 60 % MeCΝ, purity 92 %). 1H-ΝMR (DMSO-D₆) δ: 2.68 (s, 3H, CH₃), 3.17 (s, 3H, CH₃), 4.17 (m, 2H, CH₂), 7.23 (d, IH, J= 6.0 Hz, pyrimidinyl-H), 7.27 (d, IH, J= 8.0 Hz, Ph-H), 7.50 (t, IH, J= 8.0 Hz, Ph-H), 7.70 (d, IH, J= 7.5 Hz, Ph-H), 7.75 (s, IH, Ph-H), 8.44 (d, IH, J = 6.0 Hz, pyrimidinyl-H). MS (ESI*) m/z 327.37

[M+H]⁺ (C₁₆H₁₈N₆S requires 326.42).

3-[4-(2-Ethylamino-4-methyl-thiazol-5-yl)pyrimidin-2-yl-amino]benzylamine [2] Mp. 290-292 °C. Anal. RP-HPLC: t_Λ = 10.6 min (10 - 70 % MeCN, purity > 95 %). 1H-NMR (DMSO-D₆) & 1.31 (t, 3H, J= 7.0 Hz, CH₃), 2.64 (s, 3H, CH₃), 3.54 (m, 2H, CH₂), 4.11 (m, 2H, CH₂), 7.14 (d, IH, J= 6.0 Hz, pyrimidinyl-H), 7.22 (d, IH, J= 8.0 Hz, Ph-H), 7.45 (t, IH, J= 8.0 Hz, Ph-H), 7.74 (d, IH, J= 8.0 Hz, Ph-H), 7.95 (s, IH, Ph-H), 8.53 (d, IH, J = 6.0 Hz, pyrimidinyl-H). MS (ESI^1") m/z 341.20 [M+H]⁺ (C₁₇H₂₀N₆S requires 340.45).

3-[4-(2-Methylamino-4-methyl-thiazol-5-yl)pyrimidin-2-yl-amino-benzylacetamide [3] Mp. 253-255 °C. Anal. RP-HPLC: t_Λ= 11.3 min (10 - 70 % MeCN, purity > 95 %): 1H NMR (DMSO-D₆): δ 1.86 (s, 3H, CH₃), 2.46 (s, 3H, CH₃), 2.85 (s, 2H, CH₂), 3.09 (s, 3H, CH₃), 6.82 (d, IH, J= 8.0 Hz, ph-H), 6.88 (d, IH, J= 5.5 Hz, pyrimidinyl-H), 7.2 (t, IH, J= 8.0 Hz, Ph-H), 7.60 (d, IH, J= 8.0 Hz, Ph-H), 7.73 (s, IH, Ph-H), and 8.32 (d, IH, J = 5.5 Hz, pyrimidinyl-H). MS (ES ) m z 391.55 [M+Na] (C₁₈H₂₀N₆OSNa requires 391.46).

N-[4-(2, 4-Dimethyl-thiazol-5-yl)pyrimidin-2-yl] -benzene- 1 , 4-diamine [4]

Compound [4] was prepared in accordance with the methodology described in WO 01/72745. Mp. 206-208 °C. Η-NMR (DMSO-D₆) δ: 2.59 (s, 3H, CH₃), 2.62 (s, 3H, CH₃), 4.75 (brs, 2H, NH₂), 6.51 (d, 2H, J = 7.8Hz, Ph-H), 6.91 (d, IH, J = 4.9Hz, pyrimidinyl-H), 7.31 (d, 2H, J= 7.8Hz, Ph-H), 8.38 (d, IH, J= 5.4Hz, pyrimidinyl-H), 9.11 (s, IH, NH). MS (ESf) m/z 298.03 [M+H]⁺ (Cι₅H₁₅N₅S requires 297.38). [4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl]-(4-morpholin-4-yl-phenyl)~amine [5]

By condensation between 3-dimethylamino-l-(2,4-dimethyl-thiazol-5-yl)-propenone and N-(4-moφholin-4-yl-phenyl)-guanidine nitrate. Pale solid. 1H-ΝMR (CDC1₃) £: 2.69 (s, 3H, CH₃), 2.70 (s, 3H, CH₃), 3.14 (t, 4H, J= 4.8 Hz, CH₂), 3.72 (t, 4H, J= 4.9 Hz, CH₂), 6.89 (d, IH, J = 5.1 Hz, pyrimidinyl-H), 6.95 (d, 2H, J = 8.8 Hz, Ph-H), 6.98(br. s, IH, NH), 7.53 (d, 2H, J = 9.1 Hz, Ph-H), 8.38 (d, IH, J = 5.1 Hz, pyrimidinyl-H). MS (ESI^1") m/z 368 [M+H]⁺ (Cι₉H₂₁N₅OS requires 367.5).

[4-(2, 4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl]-(4-piperazin-l-yl-phenyl)-amine [6]

To a solution of l-(4-{4-[4-(2,4-dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino]-phenyl}- ρiperazin-l-yl)-ethanone (0.67 g, 1.64 mmol) in EtOH (3 mL) was added 2 M aq HCI (25 mL) in a steady stream. The mixture was heated at reflux for 1 h, cooled, and basified by addition of solid Na CO₃. The product was extracted with EtOAc. The combined organics were washed with brine, dried on Na SO₄, filtered, and evaporated to afford the title compound (580 mg) as a yellow solid. 1H-NMR (CDC1₃) £: 2.62 (s, 3H, CH₃), 2.63 (s, 3H, CH₃), 2.99 (m, 4H, CH₂), 3.06 (m, 4H, CH₂), 6.81 (d, IH, J = 5.4 Hz, pyrimidinyl-H), 6.89 (m, 3H, Ph-H, NH), 7.44 (m, 2H, Ph-H), 8.31 (d, IH, J= 5.4 Hz, pyrimidinyl-H). MS (ESI*) m z 367 (Cι₉H₂₂N₆S requires 366.5). [4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl]-[4-(4-methyl-piperazin-l-yl)-phenyl]- amine [7]

By condensation between 3-dimethylamino-l-(2,4-dimethyl-thiazol-5-yl)-propenone and N-[4-(4-methyl-piperazin-l-yl)-phenyl]-guanidine nitrate. Light yellow solid. 1H- ΝMR (CDC1₃) £: 2.37 (s, 3H, CH₃), 2.61 (m, 4H, CH₂), 2.69 (s, 3H, CH₃), 2.70 (s, 3H, CH₃), 3.20 (m, 4H, CH₂), 6.88 (d, IH, J= 5.1 Hz, pyrimidinyl-H), 6.94 (s, IH, ΝH), 6.96 (d, 2H, J= 8.8 Hz, Ph-H), 7.51 (d, 2H, J= 8.8 Hz, Ph-H), 8.38 (d, IH, J= 5.1 Hz, pyrimidinyl-H) .

2-(4-{4-[4-(2_>4-Dimethyl-thiazol-5-yl)-pyrimidin-2-ylamino]-phenyl}-piperazin-l-yl)~ ethanol [8]

Yellow solid. 1H-ΝMR (CDCI₃) & 2.55 (t, 2H, J= 5.4 Hz, CH₂), 2.62 (m, 10H, CH₃ & CH₂), 3.12 (t, 4H, J= 4.9 Hz, CH₂), 3.60 (t, 2H, J= 5.4 Hz, CH₂), 6.81 (d, IH, J= 5.4 Hz, pyrimidinyl-H), 6.88 (m, 2H, Ph-H), 7.05 (br. s, IH, NH), 7.45 (m, 2H, Ph-H), 8.30 (d, IH, J= 5.1 Hz, pyrimidinyl-H). MS (ESI*) m z 411.7 (C₂ιH₂₆N₆OS requires 410.5). [4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2-yl]-(4-piperazin-l-yl-phenyl)- amine [9]

By hydrolysis of l-(4-{4-[4-(4-Methyl-2-methylamino-thiazol-5-yl)-pyrimidin-2- ylamino] -phenyl} -piperazin-l-yl)-efhanone in 2 M aq HCI. Yellow solid. Anal. RP- HPLC: t_Λ = 8.8 min (10 - 70 % MeCN, purity > 95 %). 1H-NMR (DMSO-d₆) £: 2.45 (3, 3H, CH₃), 2.83 (t, 4H, J= 5.9Hz, CH₂), 2.85 (d, 3H, J= 4.9Hz, CH₂), 2.95 (t, 4H, J = 4.9Hz, CH₂), 6.81 (d, IH, J= 5,4Hz, pyrimidinyl-H), 6.85 (d, 2H, J= 9.3Hz, Ph-H), 7.58 (d, 2H, J= 8.8Hz, Ph-H), 7.99 (m, IH, NH), 8.26 (d, IH, J= 5.4Hz, pyrimidinyl- H), 9.14 (brs, IH). MS (ESI ) m z 382.06 [M+H]⁺ (C₁₉H₂₃N₇S requires 381.50).

Kinase assays

Compounds were investigated for their ability to inhibit the enzymatic activity of various protein kinases. This was achieved by measurement of incoφoration of radioactive phosphate from ATP into appropriate polypeptide substrates. Recombinant protein kinases and kinase complexes were produced or obtained commercially. Assays were performed using 96-well plates and appropriate assay buffers (typically 25 mM β- glycerophosphate, 20 mM MOPS, 5 mM EGTA, 1 mM DTT, 1 mM Na₃VO₃, pH 7.4), into which were added 2 - 4 μg of active enzyme with appropriate substrates. The reactions were initiated by addition of Mg/ATP mix (15 mM MgCl₂ + 100 μM ATP with 30-50 kBq per well of [γ-³²P]-ATP) and mixtures incubated as required at 30 °C. Reactions were stopped on ice, followed by filtration through p81 filteφlates or GF/C filteφlates (Whatman Polyfiltronics, Kent, UK). After washing 3 times with 75 mM aq orthophosphoric acid, plates were dried, scintillant added and incoφorated radioactivity measured in a scintillation counter (TopCount, Packard Instraments, Pangbourne, Berks, UK). Compounds for kinase assay were made up as 10 mM stocks in DMSO and diluted into 10 % DMSO in assay buffer. Data was analysed using curve-fitting software (GraphPad Prism version 3.00 for Windows, GraphPad Software, San Diego

California USA) to determine IC₅₀ values (concentration of test compound which inhibits kinase activity by 50 %).

Various modifications and variations of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific prefened embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in the relevant fields are intended to be covered by the present invention.

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Table 1. PDB coordinate file of CDK4 homology model ATOM 1 N MET 1 43. ,828 36. ,442 41.833 1. ,00 0, .00 N ATOM 2 CA MET 1 43. ,304 35, ,144 42.338 1, ,00 0, .00 C ATOM 3 C MET 1 41. ,905 34. .812 41.723 1. .00 0, .00 c ATOM 4 o MET 1 40. .864 35, .000 42.360 1, .00 0, .00 o ATOM 5 CB MET 1 43. ,308 35. .167 43.895 1, ,00 0, .00 C ATOM 6 CG MET 1 44. .697 35, ,072 44.560 1. .00 0, .00 c ATOM 7 SD MET 1 44. .518 35. .007 46.354 1, .00 0, .00 s ATOM 8 CE MET 1 46, ,164 34. ,407 46.773 1. .00 0, ,00 C ATOM 9 IH MET 1 44, .739 36. ,645 42.261 1, ,00 0, .00 H ATOM 10 2H MET 1 43, .990 36, .410 40.820 1, ,00 0, .00 H ATOM 11 HA MET 1 43, .999 34, .342 42.023 1, .00 0 .00 H TOM 12 1HB MET 1 42, ,770 36. .062 44.265 1, .00 0, .00 H ATOM 13 2HB MET 1 42, ,708 34, .316 44.269 1. .00 0, .00 H ATOM 14 1HG MET 1 45, .234 34, .170 44.213 1. ,00 0 .00 H ATOM 15 2HG MET 1 45, .329 35, .941 44.298 1, .00 0 .00 H ATOM 16 1HE MET 1 46, ,360 33, .425 46.307 1. .00 0, .00 H TOM 17 3HE MET 1 46, .940 35, .117 46.435 1, .00 0, .00 H ATOM 18 2HE MET 1 46, .261 34, .290 47.867 1, .00 0 .00 H TOM 19 N ALA 2 41. .872 34, .244 40.499 0. .00 0, .00 N ATOM 20 CA ALA 2 40, .593 33, .866 39.826 0. ,00 0, .00 c TOM 21 C ALA 2 39, .673 32, .844 40.580 0, .00 0 .00 c TOM 22 o ALA 2 38, .479 33, .098 40.720 0, .00 0 .00 o ATOM 23 CB ALA 2 40, .943 33, .402 38.400 0, .00 0, .00 c TOM 24 H ALA 2 42, .773 34, .245 40.013 0, .00 0 .00 H TOM 25 HA ALA 2 39, .984 34 .788 39.724 0, .00 0 .00 H ATOM 26 1HB ALA 2 40 .026 33 .233 37.803 0, .00 0 .00 H ATOM 27 2HB ALA 2 41, .545 34, .148 37.849 0, .00 0 .00 H TOM 28 3HB ALA 2 41, .507 32, .454 38.401 0, .00 0 .00 H ATOM 29 N THR 3 40 .229 31 .740 41.109 1, .00 0 .00 N ATOM 30 CA THR 3 39, .504 30, .798 42.028 1. .00 0, .00 c ATOM 31 C THR 3 38, .873 31, .410 43.331 1, .00 0 .00 c ATOM 32 o THR 3 37 .768 31, .013 43.705 1, .00 0 .00 0 ATOM 33 CB THR 3 40 .408 29 .572 42.370 1, .00 0 .00 c ATOM 34 0G1 THR 3 41 .644 29, .987 42.946 1. .00 0 .00 o ATOM 35 CG2 THR 3 40, .743 28, .652 41.184 1, .00 0 .00 c ATOM 36 H THR 3 41 .248 31, .716 41.031 1, .00 0 .00 H ATOM 37 HA THR 3 38 .628 30 .405 41.474 1, .00 0 .00 H ATOM 38 HB THR 3 39, .863 28, .953 43.114 1, ,00 0, .00 H ATOM 39 HG1 THR 3 42 .058 29, .192 43.293 1, .00 0 .00 H TOM 40 1HG2 THR 3 41 .364 27 .795 41.504 1, .00 0 .00 H ATOM 41 2HG2 THR 3 39, .817 28, .237 40.743 1. .00 0, .00 H ATOM 42 3HG2 THR 3 41 .287 29, .191 40.389 1, .00 0, .00 H TOM 43 N SER 4 39 .507 32, .396 43.996 1. ,00 0 .00 N ATOM 44 CA SER 4 38 .817 33 .257 45.010 1. ,00 0 .00 c ATOM 45 C SER 4 37 .565 34, .066 44.510 1, .00 0, .00 c ATOM 46 o SER 4 36 .660 34, .317 45.306 1, ,00 0, .00 o ATOM 47 CB SER 4 39 .874 34, .182 45.659 1, .00 0, .00 c ATOM 48 OG SER 4 40 .908 33, .430 46.299 1, .00 0, .00 o ATOM 49 H SER 4 40, .340 32, .724 43.499 1, ,00 0, .00 H ATOM 50 HA SER 4 38 .427 32, .596 45.811 1, .00 0, .00 H ATOM 51 1HB SER 4 40 .309 34, .872 44.910 1, .00 0, .00 H ATOM 52 2HB SER 4 39, .393 34. .836 46.413 1. ,00 0, .00 H ATOM 53 HG SER 4 40 .961 32, .592 45.827 1, ,00 0, .00 H ATOM 54 N ARG 5 37 .513 34, .476 43.229 1, ,00 0, .00 N ATOM 55 CA ARG 5 36 .352 35, .201 42.636 1. ,00 0, .00 c ATOM 56 C ARG 5 35, .350 34. .323 41.781 1. ,00 0. .00 c ATOM 57 0 ARG 5 34, .414 34. .887 41.218 1. ,00 0, .00 o ATOM 58 CB ARG 5 36, .947 36, .408 41.850 1. ,00 0, ,00 c ATOM 59 CG ARG 5 35, .983 37, .610 41.726 1. ,00 0, .00 c ATOM 60 CD ARG 5 36. .577 38, ,775 40.924 1. 00 0. .00 c ATOM 61 NE ARG 5 35, .670 39. .940 41.077 1. 00 0. .00 N ATOM 62 CZ ARG 5 35, .709 41. .055 40.363 1. 00 0. ,00 c ATOM 63 NH1 ARG 5 36.539 41 276 39.387 00 00 N

ATOM 64 NH2 ARG 5 34.870 41 978 40.674 00 00 N TOM 65 H ARG 5 38.285 34 126 42.650 00 00 H

ATOM 66 HA ARG 5 35.723 35 609 43.453 00 00 H

ATOM 67 1HB ARG 5 37.873 36 775 42.339 00 00 H

ATOM 68 2HB ARG 5 37.271 36 062 40.848 00 0.00 H

ATOM 69 1HG ARG 5 35.030 37 289 41.252 00 0.00 H

ATOM 70 2HG ARG 5 35.705 37 933 42.748 00 00 H

ATOM 71 1HD ARG 5 37.595 39 024 41.289 00 00 H

ATOM 72 2HD ARG 5 36.678 38 464 39.862 00 00 H TOM 73 HE ARG 5 34.891 39 920 41.743 00 00 H

ATOM 74 2HH1 ARG 5 37.088 40 457 39.127 00 0.00 H

ATOM 75 1HH1 ARG 5 36.394 42 110 38.812 00 0.00 H

ATOM 76 1HH2 ARG 5 34.229 41 768 41.442 00 00 H

ATOM 77 2HH2 ARG 5 34.856 42 809 40.081 00 00 H

ATOM 78 N TYR 6 35.463 32 978 41.710 00 00 N

ATOM 79 CA TYR 6 34.409 32 094 41.124 00 00 c

ATOM 80 c TYR 6 34.085 30 885 42.069 00 00 c

ATOM 81 o TYR 6 34.952 30 066 42.382 00 00 o

ATOM 82 CB TYR 6 34.735 31 702 39.646 00 00 c

ATOM 83 CG TYR 6 35.746 30 570 39.344 00 00 c TOM 84 CD1 TYR 6 35.340 29 228 39.416 00 00 c

ATOM 85 CD2 TYR 6 37.047 30 859 38.932 00 00 c

ATOM 86 CE1 TYR 6 36.231 28 203 39.112 00 00 c

ATOM 87 CE2 TYR 6 37.944 29 833 38.637 00 00 c

ATOM 88 CZ TYR 6 37.530 28 502 38.725 00 00 c

ATOM 89 OH TYR 6 38.388 27 480 38.424 00 0.00 o

ATOM 90 H TYR 6 36.283 32 591 42.189 00 0.00 H

ATOM 91 HA TYR 6 33.469 32 684 41.044 00 00 H

ATOM 92 1HB TYR 6 33.776 31 430 39.165 00 00 H

ATOM 93 2HB TYR 6 35.014 32 622 39.096 00 00 H

ATOM 94 HD1 TYR 6 34.330 28 983 39.719 1.00 00 H

ATOM 95 HD2 TYR 6 37.355 31 889 38.838 00 00 H

ATOM 96 HE1 TYR 6 35.906 27 175 39.180 00 00 H TOM 97 HE2 TYR 6 38.948 30 084 38.334 00 00 H

ATOM 98 HH TYR 6 39.147 27 924 38.056 00 00 H

ATOM 99 N GLU 7 32.820 30 746 42.490 00 00 N

ATOM 100 CA GLU 7 32.319 29 536 43.196 00 00 c

ATOM 101 C GLU 7 31.502 28 643 42.189 00 00 c

ATOM 102 o GLU 7 30.416 29 088 41.790 00 00 o

ATOM 103 CB GLU 7 31.488 30 032 44.415 00 00 c

ATOM 104 CG GLU 7 30.931 28 930 45.357 00 00 c

ATOM 105 CD GLU 7 31.977 28 165 46.169 00 00 c

ATOM 106 OE1 GLU 7 32.677 27 268 45.713 00 00 o

ATOM 107 OE2 GLU 7 32.051 28 596 47.456 00 00 o

ATOM 108 H GLU 7 32.177 31 498 42.204 00 00 H

ATOM 109 HA GLU 7 33.160 28 960 43.625 00 00 H

ATOM 110 1HB GLU 7 32.106 30 722 45.024 00 00 H

ATOM 111 2HB GLU 7 30.644 30 648 44.051 00 00 H

ATOM 112 1HG GLU 7 30.223 29 364 46.081 00 00 H

ATOM 113 2HG GLU 7 30.359 28 174 44.793 00 00 H

ATOM 114 N PRO 8 31.943 27 430 41.734 00 00 N

ATOM 115 CA PRO 8 31.156 26 597 40.779 00 00 C

ATOM 116 C PRO 8 29.841 25 981 41.377 00 00 C

ATOM 117 O PRO 8 29.863 25 111 42.250 00 00 0

ATOM 118 CB PRO 8 32.206 25 562 40.325 00 00 C

ATOM 119 CG PRO 8 33.180 25 436 41.498 00 00 C

ATOM 120 CD PRO 8 33.252 26 842 42.093 00 00 C

ATOM 121 HA PRO 8 30.897 27 213 39.894 00 00 H

ATOM 122 1HB PRO 8 31.759 24 589 40.040 1.00 0.00 H TOM 123 2HB PRO 8 32.739 25 935 39.430 00 0.00 H

ATOM 124 1HG PRO 8 32.767 24 740 42.256 00 0.00 H

ATOM 125 2HG PRO 8 34.171 25 046 41.204 1.00 0.00 H

ATOM 126 1HD PRO 8 33.404 26 795 43.192 1.00 0.00 H

ATOM 127 2HD PRO 8 34.083 27 436 41.665 1.00 0.00 H ATOM 128 N VAL 9 28.,692 26.,460 40.,881 0.,00 0.,00 N

ATOM 129 CA VAL 9 27. ,335 25. ,996 41. ,305 0. ,00 0. 00 C

ATOM 130 C VAL 9 26. 910 24. ,678 40. ,562 0. ,00 0. 00 C

ATOM 131 o VAL 9 26. ,560 23. ,690 41. ,214 0. ,00 0. ,00 o

ATOM 132 CB VAL 9 26. ,316 27. .191 41, .156 0. ,00 0. ,00 C

ATOM 133 CGI VAL 9 24. .852 26, .816 41. .490 0, .00 0. ,00 C

ATOM 134 CG2 VAL 9 26. ,653 28. ,420 42, .038 0. ,00 0. ,00 C

ATOM 135 H VAL 9 28. .823 27. .145 40. .128 0. .00 0. .00 H

ATOM 136 HA VAL 9 27. ,368 25, .733 42, ,382 0. ,00 0, .00 H

ATOM 137 HB VAL 9 26, .341 27, .520 40. .097 0. .00 0. .00 H

ATOM 138 1HG1 VAL 9 24. .159 27, ,668 41. .367 0, .00 0. .00 H

ATOM 139 2HG1 VAL 9 24. .477 26, .007 40. .835 0, .00 0, ,00 H

ATOM 140 3HG1 VAL 9 24, .751 26. .452 42, .531 0, .00 0. .00 H

ATOM 141 1HG2 VAL 9 25, .955 29, .261 41, .882 0, .00 0. ,00 H

ATOM 142 2HG2 VAL 9 26. .648 28, .170 43, .116 0. .00 0. ,00 H

ATOM 143 3HG2 VAL 9 27. .664 28. .812 41, .818 0, .00 0, .00 H

ATOM 144 N ALA 10 26. .901 24. .659 39, .215 1, .00 0, .00 N

ATOM 145 CA ALA 10 26, .608 23, .438 38, .417 1, .00 0. .00 C

ATOM 146 C ALA 10 27, .395 23, .405 37 .062 1, .00 0, .00 C

ATOM 147 o ALA 10 27, .794 24, .443 36, .525 1, .00 0. .00 o

ATOM 148 CB ALA 10 25, ,078 23, .394 38, .201 1, .00 0, .00 C

ATOM 149 H ALA 10 27, .341 25, .487 38 .796 1, .00 0. .00 H

ATOM 150 HA ALA 10 26, .913 22 .537 38 .989 1 .00 0, .00 H

ATOM 151 2HB ALA 10 24. .532 23, .350 39, .162 1, .00 0, .00 H

ATOM 152 3HB ALA 10 24. .711 24, .274 37, .642 1, .00 0. .00 H

ATOM 153 1HB ALA 10 24, .779 22 .498 37 .624 1, .00 0, .00 H

ATOM 154 N GLU 11 27, .584 22 .212 36 .469 1, .00 0, .00 N

ATOM 155 CA GLU 11 28, .048 22, .100 35, .057 1, .00 0. .00 C

ATOM 156 C GLU 11 26, .843 22 .192 34 .061 1, .00 0. .00 C

ATOM 157 o GLU 11 25, .934 21 .357 34 .081 1, .00 0. .00 0

ATOM 158 CB GLU 11 28, .889 20 .809 34 .875 1 .00 0, .00 C

ATOM 159 CG GLU 11 29 .791 20 .847 33 .610 1 .00 0, .00 C

ATOM 160 CD GLU 11 30, .646 19 .602 33 .410 1, .00 0, ,00 C

ATOM 161 OE1 GLU 11 31, .604 19 .306 34 .119 1 .00 0, .00 0

ATOM 162 0E2 GLU 11 30, .233 18 .855 32 .351 1. .00 0, .00 o

ATOM 163 H GLU 11 27 .175 21 .406 36 .949 1 .00 0, .00 H

ATOM 164 HA GLU 11 28, .750 22 .931 34 .851 1 .00 0, .00 H

ATOM 165 1HB GLU 11 29, .544 20 .652 35 .755 1, .00 0, .00 H

ATOM 166 2HB GLU 11 28 .229 19 .919 3 .846 1 .00 0, .00 H

ATOM 167 1HG GLU 11 29 .177 20 .971 32 .701 1 .00 0, .00 H

ATOM 168 2HG GLU 11 30, .478 21 .708 33 .619 1 .00 0, .00 H

ATOM 169 N I E 12 26, .859 23 .199 33 .177 0 .00 0, .00 N

ATOM 170 CA ILE 12 25 .901 23 .296 32 .026 0 .00 0, .00 C

ATOM 171 C ILE 12 26 .197 22 .224 30 .910 0 .00 0, .00 C

ATOM 172 o ILE 12 25 .268 21 .538 30 .478 0 .00 0 .00 0

ATOM 173 CB ILE 12 25, .834 24 .788 31 .522 0 .00 0, ,00 C

ATOM 174 CG2 ILE 12 2 .987 24 .992 30 .238 0 .00 0, .00 C

ATOM 175 CGI ILE 12 25 .384 25 .833 32 .592 0 .00 0, .00 C

ATOM 176 CD1 ILE 12 23 .975 25 .653 33 .195 0 .00 0, .00 C

ATOM 177 H ILE 12 27 .755 23 .699 33 .153 0 .00 0, ,00 H

ATOM 178 HA ILE 12 24 .886 23 .040 32 .388 0 .00 0, .00 H TOM 179 HB ILE 12 26 .869 25 .060 31 .235 0 .00 0, .00 H

ATOM 180 1HG2 ILE 12 24 .997 26 .051 29 .936 0 .00 0, .00 H

ATOM 181 2HG2 ILE 12 25 .467 24 .424 29 .433 0, .00 0, .00 H

ATOM 182 3HG2 ILE 12 23 .940 24 .649 30 .332 0, .00 0, .00 H

ATOM 183 1HG1 ILE 12 25 .463 26 .848 32 .156 0, .00 0, ,00 H

ATOM 184 2HG1 ILE 12 26 .122 25 .836 33 .416 0 .00 0, .00 H

ATOM 185 1HD1 ILE 12 23 .742 26 .434 33. .938 0, .00 0. .00 H

ATOM 186 2HD1 ILE 12 23, .191 25 .701 32 .415 0, .00 0, .00 H

ATOM 187 3HD1 ILE 12 23 .868 24 .675 33 .702 0, .00 0, .00 H

ATOM 188 N GLY 13 27 .457 22 .051 30 .459 0, .00 0, .00 N

ATOM 189 CA GLY 13 27 .851 20 .837 29 .691 0 .00 0, .00 C

ATOM 190 C GLY 13 29, .129 20 .943 28, .832 0, .00 0, .00 C

ATOM 191 o GLY 13 30, .035 21 .741 29, .088 0, .00 0. .00 0

ATOM 192 H GLY 13 28, .141 22 .643 30, .944 0, .00 0. ,00 H ATOM 193 1HA GLY 13 27.007 20.,510 29.051 0.00 0.,00 H

ATOM 194 2HA GLY 13 28. 007 20. ,005 30. .406 0. 00 0. ,00 H

ATOM 195 N VAL 14 29. 189 20. .089 27. ,803 1. ,00 0. .00 N

ATOM 196 CA VAL 14 30. ,268 20. .116 26. ,768 1. ,00 0, .00 C

ATOM 197 C VAL 14 29. 864 21. ,102 25. 618 1. 00 0. ,00 C

ATOM 198 o VAL 14 28. ,955 20. .832 24. ,824 1. 00 0. .00 0

ATOM 199 CB VAL 14 30. ,661 18. .676 26. ,274 1. ,00 0. .00 C

ATOM 200 CGI VAL 14 31. ,333 17. .831 27. ,380 1. ,00 0, .00 C TOM 201 CG2 VAL 14 29. ,538 17. .823 25. ,634 1. ,00 0, .00 C

ATOM 202 H VAL 14 28. ,339 19. .531 27. ,684 1. ,00 0, .00 H

ATOM 203 HA VAL 14 31. ,193 20. .512 27. ,236 1. ,00 0. .00 H

ATOM 204 HB VAL 14 31. ,428 18. .821 25. ,485 1. ,00 0. .00 H

ATOM 205 1HG1 VAL 14 30, .643 17. .632 28, .224 1, .00 0. .00 H

ATOM 206 2HG1 VAL 14 31. .680 16. .849 27, .008 1. .00 0, .00 H

ATOM 207 3HG1 VAL 14 32. ,214 18, .342 27. ,811 1, ,00 0. ,00 H

ATOM 208 2HG2 VAL 14 29, .075 18, .334 24, .770 1. .00 0, .00 H

ATOM 209 3HG2 VAL 14 29, .915 16. .851 25, .264 1. .00 0, .00 H

ATOM 210 1HG2 VAL 14 28, .724 17. .608 26, .351 1, .00 0, .00 H

ATOM 211 N GLY 15 30, .505 22, .279 25, .579 0, .00 0, .00 N

ATOM 212 CA GLY 15 30, .282 23, .278 24, .499 0, .00 0, .00 C

ATOM 213 C GLY 15 31, .352 23, .269 23, ,384 0, .00 0, .00 C

ATOM 214 o GLY 15 32. .313 22. .495 23, .406 0, .00 0, .00 0

ATOM 215 H GLY 15 31. .293 22, .321 26, .238 0, .00 0, .00 H

ATOM 216 1HA GLY 15 30, .232 24, .283 24, .954 0, .00 0, .00 H

ATOM 217 2HA GLY 15 29, .283 23, .149 24, .033 0, .00 0, .00 H

ATOM 218 N ALA 16 31, .216 24. .190 22, .418 1, .00 0, .00 N

ATOM 219 CA ALA 16 32, ,126 24, .245 21, .232 1 , .00 0, .00 C

ATOM 220 C ALA 16 33, .681 24, .295 21, .434 1, .00 0 .00 C

ATOM 221 o ALA 16 34, .413 23, .804 20, .571 1, .00 0, .00 0

ATOM 222 CB ALA 16 31, .649 25, .444 20 .393 1, .00 0 .00 C

ATOM 223 H ALA 16 30, .331 24, .723 22, .431 1, .00 0, .00 H

ATOM 224 HA ALA 16 31, .937 23, .326 20, .653 1, .00 0, .00 H

ATOM 225 2HB ALA 16 30, .561 25, .420 20, .182 1, .00 0, .00 H

ATOM 226 3HB ALA 16 31 .855 26, .405 20 .893 1, .00 0, .00 H TOM 227 1HB ALA 16 32 .140 25 .483 19 .402 1, .00 0 .00 H

ATOM 228 N TYR 17 34, .179 24, .884 22. .536 0, .00 0, .00 N

ATOM 229 CA TYR 17 35 .644 24, .930 22, .838 0, .00 0, .00 C

ATOM 230 C TYR 17 36 .029 24, .431 2 .291 0. .00 0 .00 C

ATOM 231 o TYR 17 37 .053 24 .859 24 .834 0 .00 0 .00 0

ATOM 232 CB TYR 17 36 .174 26 .365 22 .496 0 .00 0 .00 C

ATOM 233 CG TYR 17 35 .835 26 .973 21 .112 0 .00 0 .00 C

ATOM 234 GDI TYR 17 36 .416 26, .473 19, .945 0 .00 0, .00 C

ATOM 235 CE1 TYR 17 36 .058 26, .992 18 .700 0 .00 0 .00 C

ATOM 236 CZ TYR 17 35 .121 28 .020 18 .618 0 .00 0 .00 C

ATOM 237 OH TYR 17 34 .751 28 .510 17 .393 0 .00 0 .00 0

ATOM 238 CE2 TYR 17 34 .540 28 .527 19 .774 0 .00 0 .00 C

ATOM 239 CD2 TYR 17 34 .888 28, .003 21, .017 0 .00 0 .00 C

ATOM 240 H TYR 17 33 .433 25 .222 23 .144 1 .00 0 .00 H

ATOM 241 HA TYR 17 36 .183 24 .225 22 .175 0 .00 0 .00 H

ATOM 242 1HB TYR 17 37 .273 26 .366 22 .606 0 .00 0 .00 H

ATOM 243 2HB TYR 17 35 .847 2 .063 23 .287 0 .00 0 .00 H

ATOM 244 HD1 TYR 17 37 .083 25, .627 20, .002 0, .00 0, .00 H

ATOM 245 HE1 TYR 17 36 .458 26 .579 17, .788 0, .00 0, .00 H

ATOM 246 HH TYR 17 33 .979 29 .080 17, .510 0 .00 0 .00 H

ATOM 247 HE2 TYR 17 33 .795 29 .308 19, .708 0 .00 0 .00 H

ATOM 248 HD2 TYR 17 34 .400 28 .399 21 .895 0 .00 0 .00 H

ATOM 249 N GLY 18 35 .251 23 .506 2 .901 0 .00 0 .00 N

ATOM 250 CA GLY 18 35 .553 22 .906 26, .236 0, .00 0, .00 C

ATOM 251 C GLY 18 34 .325 22 .664 27, .157 0, .00 0, .00 C

ATOM 252 o GLY 18 33 .274 22 .199 26, .706 0, .00 0, .00 O

ATOM 253 H GLY 18 34 .448 23 .181 24, .339 0, .00 0, .00 H

ATOM 254 1HA GLY 18 36 .313 23 .502 26, .779 0, .00 0, .00 H

ATOM 255 2HA GLY 18 36 .025 21, .919 26, .083 0, .00 0, ,00 H

ATOM 256 N THR 19 34 .487 22, .913 28, .466 1, .00 0, .00 N TOM 257 CA THR 19 33 .418 22, .678 29, .497 1, .00 0, .00 C ATOM 258 C THR 19 32.830 24.,022 30.049 1.00 0.00 c TOM 259 0 THR 19 33. ,554 24. .916 30. ,501 1. ,00 0. 00 0 TOM 260 CB THR 19 33. ,896 21. .764 30. ,672 1. ,00 0. ,00 c

ATOM 261 OG1 THR 19 35. 086 22. ,253 31. ,276 1. ,00 0. 00 0

ATOM 262 CG2 THR 19 34. ,160 20. .299 30. ,295 1. ,00 0. 00 c

ATOM 263 H THR 19 35. ,395 23, ,297 28. ,745 1. .00 0. ,00 H

ATOM 264 HA THR 19 32. ,580 22. ,116 29. ,034 1. ,00 0. .00 H TOM 265 HB THR 19 33. ,092 21. .747 31. ,442 1. ,00 0. ,00 H

ATOM 266 HG1 THR 19 35. .250 21, .637 31, .999 1, .00 0. ,00 H

ATOM 267 1HG2 THR 19 34. ,406 19. .690 31. ,186 1. ,00 0. 00 H TOM 268 2HG2 THR 19 33. ,259 19. .835 29, .849 1. ,00 0. ,00 H

ATOM 269 3HG2 THR 19 34. .986 20, .194 29, .570 1. .00 0. ,00 H

ATOM 270 N VAL 20 31, .493 24, .142 30, .017 0. .00 0, .00 N

ATOM 271 CA VAL 20 30, .753 25, .361 30. .467 0, .00 0. ,00 C

ATOM 272 C VAL 20 30, .141 25. .104 31. .891 0, ,00 0, ,00 C

ATOM 273 0 VAL 20 29. .375 24, .156 32. .098 0, .00 0. .00 0

ATOM 274 CB VAL 20 29. .674 25. .755 29, .391 0, .00 0. ,00 C

ATOM 275 CGI VAL 20 28, .850 27, .007 29. .775 0, ,00 0. .00 C

ATOM 276 CG2 VAL 20 30, .256 26, .056 27. .988 0, .00 0. ,00 C

ATOM 277 H VAL 20 30. .983 23. .292 29. .725 0, .00 0, .00 H

ATOM 278 HA VAL 20 31, .451 26, .219 30, .537 0, .00 0, .00 H

ATOM 279 HB VAL 20 28, .963 24, .906 29, .292 0, .00 0, .00 H

ATOM 280 1HG1 VAL 20 28 .071 27, .240 29, .021 0 .00 0. .00 H

ATOM 281 2HG1 VAL 20 28, .302 26, .869 30, .726 0, .00 0, .00 H TOM 282 3HG1 VAL 20 29, .474 27, .913 29, .894 0, .00 0, .00 H

ATOM 283 1HG2 VAL 20 29, .449 26 .288 27 .263 0 .00 0, .00 H

ATOM 284 2HG2 VAL 20 30, .945 26, ,919 28, .008 0, .00 0, ,00 H

ATOM 285 3HG2 VAL 20 30, .795 25, .179 27, .584 0, .00 0, .00 H

ATOM 286 N TYR 21 30 .363 26 .042 32 .811 0 .00 0, .00 N TOM 287 CA TYR 21 29. .862 25, .934 34, .199 0. .00 0, .00 C

ATOM 288 C TYR 21 29, .124 27, .193 34, .722 0, .00 0, .00 C

ATOM 289 0 TYR 21 29 .589 28 .321 34 .534 0 .00 0, .00 0

ATOM 290 CB TYR 21 31 .083 25 .763 35 .164 0 .00 0 .00 C

ATOM 291 CG TYR 21 31 .867 24, .452 35 .099 0 .00 0, .00 C TOM 292 GDI TYR 21 31 .501 23 .367 35 .904 0 .00 0, .00 C

ATOM 293 CE1 TYR 21 32 .218 22 .175 35 .834 0 .00 0 .00 C

ATOM 294 CZ TYR 21 33 .300 22 .062 34 .967 0 .00 0, .00 C

ATOM 295 OH TYR 21 33 .924 20 .856 3 .803 0 .00 0, .00 0

ATOM 296 CE2 TYR 21 33 .698 23 .154 34 .200 0 .00 0 .00 C

ATOM 297 CD2 TYR 21 32 .980 24 .344 34 .262 0 .00 0 .00 C

ATOM 298 H TYR 21 31 .017 26 .786 32 .532 1 .00 0, .00 H

ATOM 299 HA TYR 21 29 .197 25 .056 34 .326 0 .00 0 .00 H

ATOM 300 1HB TYR 21 30 .746 25 .883 36 .215 0 .00 0 .00 H

ATOM 301 2HB TYR 21 31 .783 26 .611 35 .029 0 .00 0 .00 H

ATOM 302 HD1 TYR 21 30 .640 23 .430 36 .556 0 .00 0 .00 H

ATOM 303 HE1 TYR 21 31 .896 21 .316 36 .405 0 .00 0 .00 H

ATOM 304 HH TYR 21 33 .217 20 .184 34 .806 0 .00 0, .00 H

ATOM 305 HE2 TYR 21 34 .542 23 .070 33 .539 0 .00 0 .00 H

ATOM 306 HD2 TYR 21 33 .272 25 .175 33 .634 0 .00 0 .00 H

ATOM 307 N LYS 22 27 .941 27 .020 35 .336 0 .00 0 .00 N

ATOM 308 CA LYS 22 27 .349 28 .156 36 .096 0 .00 0 .00 C

ATOM 309 C LYS 22 28 .187 28 .436 37 .392 0 .00 0 .00 C TOM 310 0 LYS 22 28 .328 27 .553 38 .244 0 .00 0 .00 0 TOM 311 CB LYS 22 25 .867 27 .811 36 .403 0 .00 0, .00 C TOM 312 CG LYS 22 25 .084 28 .967 37 .072 0 .00 0 .00 C TOM 313 CD LYS 22 23 .611 28 .620 37 .348 0 .00 0 .00 C

ATOM 314 CE LYS 22 22 .867 29 .803 37 .984 0 .00 0 .00 C TOM 315 NZ LYS 22 21 .462 29 .427 38 .238 0 .00 0, .00 N TOM 316 H LYS 22 27 .753 26 .037 35 .588 0 .00 0 .00 H TOM 317 HA LYS 22 27 .350 29 .062 35 .452 0 .00 0 .00 H TOM 318 1HB LYS 22 25 .826 26 .900 37 .034 0 .00 0, .00 H TOM 319 2HB LYS 22 25 .363 27 .527 35 .458 0 .00 0, .00 H

ATOM 320 1HG LYS 22 25 .152 29 .869 36 .428 0 .00 0, .00 H

ATOM 321 2HG LYS 22 25 .588 29, .253 38, .019 0 .00 0, .00 H TOM 322 1HD LYS 22 23 .569 27 .721 37, .998 0 .00 0, .00 H ATOM 323 2HD LYS 22 23.130 28.320 36.392 ,00 ,00 H

ATOM 324 1HE LYS 22 22.930 30.692 37.308 ,00 ,00 H

ATOM 325 2HE LYS 22 23.379 30.125 38.920 ,00 ,00 H

ATOM 326 1HZ LYS 22 20.897 30.185 38.646 ,00 ,00 H

ATOM 327 2HZ LYS 22 20.969 29.175 37.367 ,00 ,00 H

ATOM 328 3HZ LYS 22 21.358 28.611 38.854 ,00 ,00 H

ATOM 329 N ALA 23 28.728 29.654 37.541 0.00 ,00 N

ATOM 330 CA ALA 23 29.432 30.081 38.780 0.00 .00 c

ATOM 331 C ALA 23 28.855 31.403 39.384 0.00 ,00 c TOM 332 0 ALA 23 28.536 32.352 38.661 0.00 ,00 0

ATOM 333 CB ALA 23 30.931 30.205 38.448 .00 .00 c TOM 334 H ALA 23 28.654 30.278 36.723 .00 0.00 H

ATOM 335 HA ALA 23 29.344 29.297 39.558 .00 0.00 H

ATOM 336 1HB ALA 23 31.519 30.458 39.350 .00 00 H

ATOM 337 2HB ALA 23 31.345 29.259 38.052 .00 00 H

ATOM 338 3HB ALA 23 31.129 30.996 37.700 .00 0.00 H

ATOM 339 N ARG 24 28.765 31.479 40.722 .00 0.00 N

ATOM 340 CA ARG 24 28.560 32.771 41.440 .00 0.00 c

ATOM 341 C ARG 24 29.929 33.460 41.762 .00 0.00 c

ATOM 342 0 ARG 24 30.925 32.787 42.043 .00 0.00 o

ATOM 343 CB ARG 24 27.751 32.462 42.730 0.00 0.00 c

ATOM 344 CG ARG 24 27.196 33.705 43.473 0.00 00 c

ATOM 345 CD ARG 24 26.462 33.331 44.768 0.00 00 c

ATOM 346 NE ARG 24 26.038 34.576 45.457 0.00 00 N

ATOM 347 CZ ARG 24 25.492 34.642 46.665 00 00 c

ATOM 348 NH1 ARG 24 25.240 33.611 47.415 00 00 N TOM 349 NH2 ARG 24 25.197 35.808 47.120 00 00 N

ATOM 350 H ARG 24 29.245 30.695 41.188 00 00 H

ATOM 351 HA ARG 24 27.960 33.460 40.808 00 00 H

ATOM 352 1HB ARG 24 28.391 31.863 43.411 00 00 H

ATOM 353 2HB ARG 24 26.910 31.791 42.478 00 00 H

ATOM 354 1HG ARG 24 26.531 34.274 42.789 00 00 H

ATOM 355 2HG ARG 24 28.036 34.393 43.704 0.00 00 H TOM 356 1HD ARG 24 27.145 32.729 45.407 0.00 00 H

ATOM 357 2HD ARG 24 25.593 32.680 44.534 ,00 00 H TOM 358 HE ARG 24 26.167 35.482 44.994 ,00 00 H

ATOM 359 1HH1 ARG 24 24.842 33.763 48.341 ,00 00 H

ATOM 360 2HH1 ARG 24 25.533 32.722 47.002 0.00 00 H

ATOM 361 1HH2 ARG 24 24.790 35.861 48.054 0.00 0.00 H TOM 362 2HH2 ARG 24 25.416 36.599 46.511 0.00 0.00 H

ATOM 363 N ASP 25 29.971 34.797 41.766 1.00 00 N

ATOM 364 CA ASP 25 31.220 35.559 42.050 00 00 C

ATOM 365 C ASP 25 31.253 36.064 43.543 00 00 C

ATOM 366 0 ASP 25 30.700 37.140 43.788 00 00 0

ATOM 367 CB ASP 25 31.321 36.705 41.002 1.00 00 C

ATOM 368 CG ASP 25 31.525 36.287 39.541 1.00 00 C

ATOM 369 OD1 ASP 25 32.048 35.239 39.176 00 00 0

ATOM 370 OD2 ASP 25 31.064 37.226 38.673 00 00 0 TOM 371 H ASP 25 29.245 35.236 41.183 00 00 H

ATOM 372 HA ASP 25 32.104 34.924 41.876 00 00 H

ATOM 373 1HB ASP 25 30.433 37.360 41.057 00 00 H

ATOM 374 2HB ASP 25 32.175 37.357 41.251 00 00 H TOM 375 N RO 26 31.873 35.387 44.572 00 00 N

ATOM 376 CA PRO 26 31.818 35.830 46.009 00 00 C

ATOM 377 C RO 26 32.186 37.312 46.351 00 00 c

ATOM 378 0 PRO 26 31.610 37.865 47.290 00 00 0

ATOM 379 CB PRO 26 32.556 34.718 46.776 00 00 c

ATOM 380 CG PRO 26 33.318 33.931 45.711 00 00 c

ATOM 381 CD PRO 26 32.497 34.059 44.432 00 00 c

ATOM 382 HA PRO 26 30.755 35.758 46.309 00 00 H

ATOM 383 1HB RO 26 33.231 35.104 47.565 00 00 H

ATOM 384 2HB PRO 26 31.830 34.054 47.284 00 00 H

ATOM 385 1HG PRO 26 34.306 34.392 45.553 00 00 H

ATOM 386 2HG PRO 26 33.501 32.875 45.993 00 00 H

ATOM 387 1HD PRO 26 33.135 33.952 43.535 00 00 H ATOM 388 2HD PRO 26 31.724 33.267 44.382 1.00 0,,00 H

ATOM 389 N HIS 27 33. 157 37. ,932 45. ,651 1. ,00 0, ,00 N

ATOM 390 CA HIS 27 33. 401 39. 400 45. 806 1. 00 0. ,00 C

ATOM 391 C HIS 27 32. 200 40. 339 45. ,400 1. ,00 0, ,00 C

ATOM 392 0 HIS 27 31. 973 41. ,346 46. ,075 1. ,00 0, .00 O

ATOM 393 CB HIS 27 34. 713 39. 709 45. ,030 1. ,00 0. ,00 C

ATOM 394 CG HIS 27 35. 252 41. ,131 45. .193 1. ,00 0. .00 C

ATOM 395 ND1 HIS 27 35. ,050 42. ,131 44. ,253 1. .00 0. ,00 N

ATOM 396 CE1 HIS 27 35. 684 43. ,165 44. ,889 1. .00 0, ,00 C

ATOM 397 NE2 HIS 27 36. 273 42. ,961 46. ,109 1. .00 0. ,00 N

ATOM 398 CD2 HIS 27 35. ,975 41. ,622 46. .294 1, .00 0. .00 C

ATOM 399 H HIS 27 33. 454 37. ,374 44. ,844 1. .00 0. .00 H

ATOM 400 HA HIS 27 33. ,589 39. ,602 46, ,880 1. .00 0. .00 H

ATOM 401 1HB HIS 27 35. ,511 39, .004 45. ,336 1. ,00 0, .00 H

ATOM 402 2HB HIS 27 34. ,551 39. ,510 43. ,956 1. ,00 0. .00 H

ATOM 403 HE1 HIS 27 35. ,699 44, .146 44. .431 1. ,00 0, ,00 H

ATOM 404 HE2 HIS 27 36. ,740 43. .630 46. .731 1, ,00 0, .00 H

ATOM 405 HD2 HIS 27 36. ,232 41. ,038 47. .168 1. .00 0. .00 H

ATOM 406 N SER 28 31. ,477 40. ,049 44. ,301 1. .00 0, .00 N

ATOM 407 CA SER 28 30. .413 40. .941 43. .747 1. .00 0, .00 C

ATOM 408 C SER 28 28. ,925 40. ,436 43. .791 1. ,00 0, .00 C

ATOM 409 0 SER 28 28. .018 41, .270 43. .728 1. .00 0, .00 O

ATOM 410 CB SER 28 30. .849 41, .338 42. .312 1. .00 0, .00 C

ATOM 411 OG SER 28 30. .747 40, .257 41, .375 1, .00 0 .00 O

ATOM 412 H SER 28 31. ,668 39, ,126 43, .893 1. ,00 0, .00 H

ATOM 413 HA SER 28 30, .386 41, .887 44, .323 1, .00 0 .00 H

ATOM 414 1HB SER 28 30, .213 42, .175 41, .962 1, .00 0 .00 H

ATOM 415 2HB SER 28 31, .878 41, .743 42, .312 1, .00 0, .00 H

ATOM 416 HG SER 28 30, .190 40, .537 40, .630 1, .00 0 .00 H

ATOM 417 N GLY 29 28, .648 39, .120 43 .855 0, .00 0 .00 N

ATOM 418 CA GLY 29 27, .263 38, .566 43, .740 0, .00 0, .00 C

ATOM 419 C GLY 29 26, .686 38, .224 42, .339 0, .00 0 .00 C

ATOM 420 0 GLY 29 25, .495 37 .923 42, .240 0, .00 0 .00 O

ATOM 421 H GLY 29 29, .495 38, .526 43, .843 0, .00 0, .00 H

ATOM 422 1HA GLY 29 26, .538 39, .241 44, .234 0, .00 0 .00 H

ATOM 423 2HA GLY 29 27, .225 37 .634 44 .327 0, .00 0 .00 H

ATOM 424 N HIS 30 27, .490 38, .259 41, .266 1. .00 0, .00 N

ATOM 425 CA HIS 30 27, .004 38, .057 39, .872 1, .00 0 .00 C

ATOM 426 C HIS 30 27 .125 36 .568 39 .408 1, .00 0 .00 C

ATOM 427 0 HIS 30 28, .143 35, ,904 39. .629 1, .00 0, .00 O

ATOM 428 CB HIS 30 27 .772 39, .011 38, .911 1, .00 0 .00 C

ATOM 429 CG HIS 30 27 .531 40 .508 39 .126 1 .00 0 .00 C

ATOM 430 ND1 HIS 30 28 .486 41 .358 39 .664 1 .00 0 .00 N

ATOM 431 CE1 HIS 30 27 .727 42, .496 39 .778 1, .00 0 .00 C

ATOM 432 NE2 HIS 30 26 .426 42 .497 39 .349 1, .00 0 .00 N

ATOM 433 CD2 HIS 30 26 .313 41 .184 38 .932 1 .00 0 .00 C

ATOM 434 H HIS 30 28 .450 38 .567 41, .460 1, .00 0 .00 H

ATOM 435 HA HIS 30 25 .934 38 .347 39 .816 1, .00 0 .00 H

ATOM 436 1HB HIS 30 28 .859 38 .790 38 .958 1 .00 0 .00 H

ATOM 437 2HB HIS 30 27 .508 38 .777 37 .862 1, .00 0 .00 H

ATOM 438 HE1 HIS 30 28 .161 43 .389 40 .209 1 .00 0 .00 H

ATOM 439 HE2 HIS 30 25 .722 43 .242 39 .388 1 .00 0 .00 H

ATOM 440 HD2 HIS 30 25 .410 40 .725 38 .551 1, .00 0 .00 H

ATOM 441 N PHE 31 26 .088 36 .064 38 .720 1 .00 0 .00 N

ATOM 442 CA PHE 31 26 .089 3 .694 38 .132 1 .00 0 .00 C

ATOM 443 C PHE 31 26 .586 34 .721 36 .649 1, .00 0 .00 C

ATOM 444 O PHE 31 26 .087 35 .478 35 .809 1 .00 0 .00 O

ATOM 445 CB PHE 31 24 .681 34 .048 38 .260 1, .00 0 .00 C

ATOM 446 CG PHE 31 24 .253 33, .706 39. .699 1, .00 0, .00 C

ATOM 447 CD1 PHE 31 23 .486 34 .615 40, .435 1, .00 0 .00 C

ATOM 448 CE1 PHE 31 23 .130 34 .332 41 .751 1, .00 0 .00 C

ATOM 449 CZ PHE 31 23 .524 33 .132 42 .335 1, .00 0 .00 C

ATOM 450 CE2 PHE 31 24 .275 32, .214 41, .605 1, .00 0, .00 C

ATOM 451 CD2 PHE 31 2 .651 32, .504 40, .295 1, .00 0 .00 C

ATOM 452 H PHE 31 25 .344 36, .737 38 .520 1, .00 0 .00 H ATOM 453 HA PHE 31 26 . 781 34.055 38.717 00 0.00 H

ATOM 454 1HB PHE 31 23 . 930 34.699 37.770 00 0.00 H

ATOM 455 2HB PHE 31 24 . 658 33.124 37.653 00 00 H

ATOM 456 HD1 PHE 31 23 . 185 35.557 39.995 00 00 H

ATOM 457 HE1 PHE 31 22 . 548 35.049 42.314 00 00 H TOM 458 HZ PHE 31 23 . 241 32.913 43.354 00 00 H

ATOM 459 HE2 PHE 31 24 . 585 31.286 42.063 00 0.00 H

ATOM 460 HD2 PHE 31 25 . 279 31.810 39.752 00 0.00 H

ATOM 461 N VAL 32 27 . 581 33.881 36.342 00 00 N

ATOM 462 CA VAL 32 28 . 341 33.926 35.056 00 00 c

ATOM 463 C VAL 32 28 . 394 32.514 34.377 00 00 c

ATOM 464 o VAL 32 28 . 539 31.476 35.035 00 00 0

ATOM 465 CB VAL 32 29 . 770 34.560 35.243 00 00 c

ATOM 466 CGI VAL 32 29 . 716 36.088 35.468 00 00 c

ATOM 467 CG2 VAL 32 30 . 649 33.928 36.348 0.00 00 c

ATOM 468 H VAL 32 28 . Oil 33.431 37.164 0.00 00 H

ATOM 469 HA VAL 32 27 . 807 34.588 34.343 00 00 H

ATOM 470 HB VAL 32 30 . 318 34.424 34.290 00 00 H

ATOM 471 1HG1 VAL 32 30 . 724 36.537 35.534 00 00 H

ATOM 472 2HG1 VAL 32 29 . 183 36.612 34.653 00 00 H

ATOM 473 3HG1 VAL 32 29 . 210 36.347 36.418 00 00 H

ATOM 474 1HG2 VAL 32 31 . 647 34.395 36.418 00 00 H

ATOM 475 2HG2 VAL 32 30 . 206 34.058 37.355 00 00 H

ATOM 476 3HG2 VAL 32 30 . 801 32.846 36.192 00 0.00 H

ATOM 477 N ALA 33 28 . 313 32.483 33.035 00 0.00 N

ATOM 478 CA ALA 33 28 . 662 31.282 32.234 00 00 c

ATOM 479 C ALA 33 30.213 31.157 32.051 00 00 c

ATOM 480 o ALA 33 30.846 31.815 31.220 00 00 0

ATOM 481 CB ALA 33 27.862 31.374 30.922 00 00 c

ATOM 482 H ALA 33 28.329 33.425 32.612 00 00 H

ATOM 483 HA ALA 33 28.295 30.367 32.746 0.00 0.00 H

ATOM 484 1HB ALA 33 28.095 30.535 30.241 0.00 0.00 H

ATOM 485 2HB ALA 33 26.770 31.342 31.096 00 00 H

ATOM 486 3HB ALA 33 28.065 32.308 30.365 00 00 H

ATOM 487 N LEU 34 30.818 30.336 32.910 00 0.00 N

ATOM 488 CA LEU 34 32.286 30.202 33.055 00 0.00 c

ATOM 489 C LEU 34 32.840 29.057 32.139 00 00 c

ATOM 490 o LEU 34 32.585 27.873 32.382 00 00 o

ATOM 491 CB LEU 34 32.509 29.924 34.570 00 00 c

ATOM 492 CG LEU 34 33.976 30.056 35.045 00 00 c

ATOM 493 CD1 LEU 34 34.296 31.507 35.443 00 0.00 c

ATOM 494 CD2 LEU 34 34.243 29.127 36.231 00 0.00 c

ATOM 495 H LEU 34 30.181 29.863 33.569 00 00 H

ATOM 496 HA LEU 34 32 777 31.165 32.805 00 00 H

ATOM 497 1HB LEU 34 32 123 28.911 34.793 00 00 H TOM 498 2HB LEU 34 31.870 30.582 35.197 00 00 H

ATOM 499 HG LEU 34 34.660 29.749 34.229 00 00 H

ATOM 500 1HD1 LEU 34 35.334 31.627 35.799 00 00 H

ATOM 501 2HD1 LEU 34 34.160 32.204 34.595 00 00 H

ATOM 502 3HD1 LEU 34 33.638 31.872 36.258 00 00 H

ATOM 503 1HD2 LEU 34 35.302 29.169 36.542 00 00 H

ATOM 504 2HD2 LEU 34 33.628 29.395 37.111 00 00 H

ATOM 505 3HD2 LEU 34 34.022 28.071 35.989 00 00 H

ATOM 506 N LYS 35 33.588 29.413 31.083 00 00 N

ATOM 507 CA LYS 35 34.104 28.423 30.096 0.00 00 C

ATOM 508 C LYS 35 35.611 28.069 30.347 0.00 00 C

ATOM 509 o LYS 35 36.502 28.912 30.184 00 00 O

ATOM 510 CB LYS 35 33 - 829 29.002 28.684 00 00 C

ATOM 511 CG LYS 35 33.955 27.977 27.536 00 00 C

ATOM 512 CD LYS 35 33.581 28.590 26.170 00 0.00 C

ATOM 513 CE LYS 35 33.484 27.557 25.037 00 0.00 C TOM 514 NZ LYS 35 32.231 26.780 25.135 0.00 0.00 N

ATOM 515 H LYS 35 33.707 30.432 30.984 0.00 0.00 H

ATOM 516 HA LYS 35 33 .513 27.486 30.168 00 0.00 H

ATOM 517 1HB LYS 35 34.491 29.867 28.504 00 0.00 H ATOM 518 2HB LYS 35 32.801 29..423 28.,660 0.00 0.00 H

ATOM 519 1HG LYS 35 33. 307 27. 108 27. ,769 0. 00 0. 00 H

ATOM 520 2HG LYS 35 34. 985 27. 565 27. ,507 0. 00 0. 00 H

ATOM 521 1HD LYS 35 34. 335 29. ,355 25. .905 0. ,00 0. .00 H

ATOM 522 2HD LYS 35 32. 632 29. 167 26. ,242 0. 00 0. 00 H

ATOM 523 1HE LYS 35 34. 376 26. ,894 25. .040 0. .00 0. ,00 H

ATOM 524 2HE LYS 35 33. ,504 28. ,096 24, .062 0. ,00 0. .00 H

ATOM 525 1HZ LYS 35 32. 033 26. ,108 24. ,383 1. .00 0. ,00 H

ATOM 526 2HZ LYS 35 32. ,055 26. ,315 26. .035 1. ,00 0. ,00 H

ATOM 527 3HZ LYS 35 31. .408 27, .415 25. .018 1, ,00 0. .00 H

ATOM 528 N SER 36 35. ,916 26. ,826 30, .805 1. ,00 0. ,00 N

ATOM 529 CA SER 36 37. ,312 26. .258 30. .799 1. .00 0. .00 C

ATOM 530 C SER 36 37. ,710 26. .072 29. .301 1. ,00 0, ,00 C

ATOM 531 0 SER 36 37. ,067 25, .278 28. .602 1, ,00 0. .00 O

ATOM 532 CB SER 36 37. ,323 24, .980 31, .660 1, ,00 0. .00 C

ATOM 533 OG SER 36 38, ,645 24. .449 31, .767 1. .00 0, ,00 O

ATOM 534 H SER 36 35. .090 26. .219 30. .928 1, .00 0, ,00 H

ATOM 535 HA SER 36 37, ,994 26. .987 31, .278 1, ,00 0, .00 H

ATOM 536 1HB SER 36 36. .932 25, .194 32, .675 1, .00 0, .00 H

ATOM 537 2HB SER 36 36. .638 24, .219 31, .238 1. .00 0. .00 H

ATOM 538 HG SER 36 38. .855 24, .063 30, .909 1. .00 0, .00 H

ATOM 539 N VAL 37 38, .811 26, .708 28, .841 1, .00 0, .00 N

ATOM 540 CA VAL 37 39. .037 26, ,800 27, .354 1, .00 0. .00 C

ATOM 541 C VAL 37 40. .481 26, .430 26, .812 1, .00 0, .00 C

ATOM 542 0 VAL 37 41, .495 26. .608 27, .493 1, .00 0, .00 O

ATOM 543 CB VAL 37 38, .561 28, .245 26, .931 1, .00 0, .00 C

ATOM 544 CGI VAL 37 39, .654 29, .335 27, .028 1, .00 0, .00 C

ATOM 545 CG2 VAL 37 37. .964 28, .290 25, .512 1. .00 0. .00 C

ATOM 546 H VAL 37 39, .209 27, .398 29, .488 1, .00 0, .00 H

ATOM 547 HA VAL 37 38, .365 26, .080 26 .843 1 .00 0, .00 H

ATOM 548 HB VAL 37 37, .724 28, .564 27, .591 1, .00 0, .00 H

ATOM 549 1HG1 VAL 37 40, .547 29, ,112 26, .420 1, .00 0, .00 H

ATOM 550 2HG1 VAL 37 39 .296 30 .327 26 .702 1 .00 0 .00 H

ATOM 551 3HG1 VAL 37 39, .997 29, .453 28, .073 1, .00 0, .00 H

ATOM 552 2HG2 VAL 37 37, .191 27 .512 25 .373 1 .00 0 .00 H

ATOM 553 3HG2 VAL 37 37 .470 29 .257 25 .309 1 .00 0 .00 H

ATOM 554 1HG2 VAL 37 38, .727 28 .145 24 .725 1, .00 0, .00 H

ATOM 555 N ARG 38 40 .567 25 .989 25 .545 0 .00 0 .00 N

ATOM 556 CA ARG 38 41 .843 25 .586 24 .854 0 .00 0 .00 C

ATOM 557 C ARG 38 42, .714 26 .685 24 .126 0 .00 0 .00 C

ATOM 558 O ARG 38 43 .438 26 .356 23 .181 0 .00 0 .00 O

ATOM 559 CB ARG 38 41 .334 24 .597 23 .748 0 .00 0 .00 C

ATOM 560 CG ARG 38 40, .480 25 .207 22 .577 0 .00 0, .00 C

ATOM 561 CD ARG 38 40 .713 24 .512 21 .234 0 .00 0 .00 C

ATOM 562 NE ARG 38 39 .982 25 .195 20 .137 0 .00 0 .00 N

ATOM 563 CZ ARG 38 39, .924 24 .763 18 .880 0 .00 0. .00 C

ATOM 564 NH1 ARG 38 40 .450 23 .649 18 .467 0 .00 0 .00 N

ATOM 565 NH2 ARG 38 39 .322 25 .498 18 .015 0 .00 0 .00 N

ATOM 566 H ARG 38 39, .648 25 .838 25, .117 0 .00 0 .00 H

ATOM 567 HA ARG 38 42 .508 25 .046 25 .557 0 .00 0 .00 H

ATOM 568 1HB ARG 38 42 .235 24 .099 23 .335 0 .00 0 .00 H

ATOM 569 2HB ARG 38 40 .798 23 .752 24, .216 0, .00 0, .00 H

ATOM 570 1HG ARG 38 39 .408 25 .169 22 .853 0 .00 0 .00 H

ATOM 571 2HG ARG 38 40 .703 26 .287 22 .460 0 .00 0 .00 H

ATOM 572 1HD ARG 38 41, .804 24 .508 21, .020 0, .00 0, .00 H

ATOM 573 2HD ARG 38 40 .408 23 .455 21 .330 0 .00 0 .00 H

ATOM 574 HE ARG 38 39 .513 26 .094 20 .294 1 .00 0 .00 H

ATOM 575 1HH1 ARG 38 40 .468 23 .443 17, .464 0, .00 0, .00 H

ATOM 576 2HH1 ARG 38 40 .944 23 .137 19 .199 0, .00 0 .00 H

ATOM 577 1HH2 ARG 38 38 .909 26 .371 18 .358 0 .00 0 .00 H

ATOM 578 2HH2 ARG 38 39, .262 25 .126 17, .069 0, .00 0, .00 H

ATOM 579 N VAL 39 42, .751 27 .943 24, .577 0, .00 0 .00 N

ATOM 580 CA VAL 39 43 .412 29 .048 23 .790 0, .00 0 .00 C

ATOM 581 C VAL 39 44, .947 28, .916 23, .373 0, .00 0, .00 C

ATOM 582 O VAL 39 45, .201 29. .076 22, .172 0, .00 0, .00 O ATOM 583 CB VAL 39 42.955 30.409 24.445 0.00 0.00 c

ATOM 584 CGI VAL 39 43. ,821 31. 655 24. ,163 0. 00 0. 00 c

ATOM 585 CG2 VAL 39 41. 504 30. 798 24. 065 0. 00 0. 00 c

ATOM 586 H VAL 39 42. ,146 28. 106 25. ,390 0. 00 0. 00 H

ATOM 587 HA VAL 39 42. ,918 29. 037 22. ,797 0. 00 0. ,00 H

ATOM 588 HB VAL 39 42. 981 30. 277 25. ,541 0. 00 0. 00 H

ATOM 589 1HG1 VAL 39 44. ,864 31. 518 24. ,503 0. 00 0. ,00 H

ATOM 590 2HG1 VAL 39 43, ,862 31. ,902 23. .090 0. ,00 0. ,00 H

ATOM 591 3HG1 VAL 39 43. ,438 32. 555 24. ,681 0. 00 0. ,00 H

ATOM 592 1HG2 VAL 39 41. ,146 31. 685 24. .625 0. ,00 0. ,00 H

ATOM 593 2HG2 VAL 39 41, ,403 31. ,036 22. ,990 0. ,00 0, ,00 H

ATOM 594 3HG2 VAL 39 40, ,781 29. 98£> 24. .275 0. ,00 0. ,00 H

ATOM 595 N PRO 40 45, .975 28. 670 24. .255 0. ,00 0, ,00 N

ATOM 596 CA PRO 40 47, .387 28. ,424, 23. .820 0. ,00 0, ,00 C

ATOM 597 CD PRO 40 45, ,801 28. 61S 25. .721 0. .00 0, .00 C

ATOM 598 C PRO 40 47, ,563 27. ,001 23. .164 0. ,00 0, ,00 C

ATOM 599 O PRO 40 47, ,590 25, ,952 23. .811 0. .00 0, .00 O

ATOM 600 CB PRO 40 48. .163 28. 690 25, .123 0. ,00 0. .00 C

ATOM 601 CG PRO 40 47. ,203 28, ,294= 26, .244 0. .00 0, ,00 C

ATOM 602 HA PRO 40 47, ,695 29. ,208 23. .100 0. ,00 0, .00 H

ATOM 603 1HD PRO 40 45, ,078 27, ,839 26. .038 0, ,00 0, .00 H

ATOM 604 2HD PRO 40 45, .448 29, ,588 26, .115 0, ,00 0, .00 H

ATOM 605 1HB PRO 40 49, .124 28, ,139 25, .181 0. .00 0, .00 H

ATOM 606 2HB PRO 40 48, .421 29. ,763 25 .209 0, .00 0, .00 H

ATOM 607 1HG PRO 40 47, ,294 27, ,209 26, .424 0, ,00 0, .00 H

ATOM 608 2HG PRO 40 47, .434 28. .790 27, .206 0, .00 0, .00 H

ATOM 609 N ASN 41 47, .723 27, .029 21 .841 0, .00 0, .00 N

ATOM 610 CA ASN 41 47, .794 25, ,827 20, .968 0. .00 0, .00 C

ATOM 611 C ASN 41 48, .925 24, ,749 20 .879 0, .00 0, .00 C

ATOM 612 0 ASN 41 48 .527 23, ,595 20 .681 0, .00 0, .00 O

ATOM 613 CB ASN 41 47, .682 26, ,480 19, .536 0, .00 0, .00 C

ATOM 614 CG ASN 41 47, .705 25. ,659 18 .228 0, .00 0, .00 C

ATOM 615 ODl ASN 41 48 .174 26, • 130 17 .201 0, .00 0 .00 O

ATOM 616 ND2 ASN 41 47, .237 24. ,439 18, .166 0, .00 0, .00 N

ATOM 617 H ASN 41 47 .554 27, .963 21 .459 0, .00 0, .00 H

ATOM 618 HA ASN 41 46 .863 25, .253 21 .152 0 .00 0 .00 H

ATOM 619 1HB ASN 41 46, .780 27, .111 19 .466 0, .00 0, .00 H

ATOM 620 2HB ASN 41 48 .516 27, .200 19 .414 0, .00 0 .00 H

ATOM 621 1HD2 ASN 41 47 .547 23, .974 17 .309 0 .00 0 .00 H

ATOM 622 2HD2 ASN 41 47. .091 23, .975 19 .072 0, .00 0 .00 H

ATOM 623 N GLY 42 50 .243 24, .995 21 .036 0 .00 0 .00 N

ATOM 624 CA GLY 42 51 .198 23, .921. 20 .605 0 .00 0 .00 C

ATOM 625 C GLY 42 51 .307 22 .575 21 .379 0 .00 0 .00 C

ATOM 626 0 GLY 42 51 .406 21, .525 20 .748 0 .00 0 .00 0

ATOM 627 H GLY 42 50 .486 25, .987 21 .148 0 .00 0 .00 H

ATOM 628 1HA GLY 42 50 .996 23 .662 19 .547 0 .00 0 .00 H

ATOM 629 2HA GLY 42 52 .216 24, .348 20 .561 0 .00 0 .00 H

ATOM 630 N GLY 43 51 .305 22, .603 22 .720 0 .00 0 .00 N

ATOM 631 CA GLY 43 51 .105 21 .373 23 .538 0 .00 0 .00 C

ATOM 632 C GLY 43 52 .291 20, .411 23 .770 0 .00 0 .00 C

ATOM 633 0 GLY 43 52 .789 20, .322 24 .891 0 .00 0 .00 O

ATOM 634 H GLY 43 51 .088 23 .537 23 .084 0 .00 0 .00 H

ATOM 635 1HA GLY 43 50 .748 21, .685 24 .537 0 .00 0 .00 H

ATOM 636 2HA GLY 43 50 .257 20, .784 23 .138 0 .00 0 .00 H

ATOM 637 N GLY 44 52 .694 19 .652 22 .738 0 .00 0 .00 N

ATOM 638 CA GLY 44 53 .625 18, .486 22 .874 0 .00 0 .00 C

ATOM 639 C GLY 44 5 .992 18, .665 23 .572 0 .00 0 .00 C

ATOM 640 0 GLY 44 55 .296 17 .964 24 .538 0 .00 0 .00 O

ATOM 641 H GLY 44 52 .228 19, .914 21 .857 0 .00 0 .00 H

ATOM 642 1HA GLY 44 53 .093 17, .672 23 .403 0 .00 0 .00 H

ATOM 643 2HA GLY 44 53 .820 18 .065 21 .870 0 .00 0 .00 H

ATOM 644 N GLY 45 55 .812 19 .594 23 .065 0 .00 0 .00 N

ATOM 645 CA GLY 45 57 .106 19, .964 23 .707 0 .00 0 .00 C

ATOM 646 C GLY 45 57 .298 21, .477 23 .918 0 .00 0 .00 C

ATOM 647 0 GLY 45 58 .202 22, .067 23 .328 0 .00 0 .00 O ATOM 648 H GLY 45 55.388 20.130 22.299 0.00 0.00 H

ATOM 649 1HA GLY 45 57.264 19.454 24.677 0.00 0.00 H

ATOM 650 2HA GLY 45 57.934 19.599 23.070 00 0.00 H

ATOM 651 N GLY 46 56.440 22.101 24.737 00 0.00 N

ATOM 652 CA GLY 46 56.483 23.568 24.977 00 0.00 c

ATOM 653 C GLY 46 55.085 24.210 24.890 00 0.00 c

ATOM 654 0 GLY 46 54.332 24.228 25.866 00 0.00 0

ATOM 655 H GLY 46 55.609 21.522 24.919 00 0.00 H

ATOM 656 1HA GLY 46 56.921 23.786 25.961 00 0.00 H

ATOM 657 2HA GLY 46 57.171 24.087 24.277 00 00 H

ATOM 658 N GLY 47 54.752 24.750 23.715 00 00 N

ATOM 659 CA GLY 47 53.427 25.386 23.470 00 00 c

ATOM 660 C GLY 47 53.495 26.878 23.119 0.00 00 C

ATOM 661 0 GLY 47 53.445 27.229 21.937 0.00 0.00 0

ATOM 662 H GLY 47 55.467 24.655 22.985 00 0.00 H

ATOM 663 1HA GLY 47 52.950 24.873 22.623 00 ,00 H

ATOM 664 2HA GLY 47 52.718 25.243 24.311 00 00 H

ATOM 665 N GLY 48 53.582 27.749 24.128 00 ,00 N

ATOM 666 CA GLY 48 53.651 29.215 23.909 00 ,00 c

ATOM 667 C GLY 48 53.118 30.041 25.092 00 ,00 c

ATOM 668 0 GLY 48 52.002 29.825 25.568 00 0.00 0

ATOM 669 H GLY 48 53.560 27.331 25.070 00 0.00 H

ATOM 670 1HA GLY 48 54.694 29.496 23.665 00 00 H

ATOM 671 2HA GLY 48 53.054 29.515 23.026 00 00 H

ATOM 672 N LEU 49 53.869 31.063 25.522 00 00 N

ATOM 673 CA LEU 49 53.318 32.136 26.405 00 00 c

ATOM 674 C LEU 49 52.088 32.928 25.787 00 00 c

ATOM 675 0 LEU 49 51.995 32.987 24.554 00 00 0

ATOM 676 CB LEU 49 54.516 32.990 26.924 00 00 c

ATOM 677 CG LEU 49 55.422 33.773 25.931 00 00 c

ATOM 678 GDI LEU 49 54.741 35.016 25.334 00 00 c

ATOM 679 CD2 LEU 49 56.709 34.219 26.648 00 00 c

ATOM 680 H LEU 49 54.791 31.147 25.087 00 00 H

ATOM 681 HA LEU 49 52.920 31.614 27.298 00 00 H

ATOM 682 1HB LEU 49 54.163 33.690 27.701 00 00 H

ATOM 683 2HB LEU 49 55.161 32.296 27.503 00 00 H

ATOM 684 HG LEU 49 55.722 33.101 25.103 00 00 H

ATOM 685 1HD1 LEU 49 55.433 35.593 24.693 0.00 00 H

ATOM 686 2HD1 LEU 49 53.882 34.748 24.695 0.00 00 H

ATOM 687 3HD1 LEU 49 54.369 35.703 26.117 00 00 H

ATOM 688 1HD2 LEU 49 57.407 34.745 25.970 00 00 H

ATOM 689 2HD2 LEU 49 56.510 34.894 27.501 00 00 H

ATOM 690 3HD2 LEU 49 57.271 33.355 27.057 00 00 H

ATOM 691 N PRO 50 51.104 33.494 26.554 00 0.00 N

ATOM 692 CA PRO 50 49.820 34.009 25.978 00 0.00 c

ATOM 693 CD PRO 50 51.135 33.514 28.030 00 0.00 c

ATOM 694 C PRO 50 49.958 35.203 24.969 00 0.00 c

ATOM 695 0 PRO 50 50.062 36.365 25.372 00 0.00 o

ATOM 696 CB PRO 50 49.017 34.331 27.259 00 0.00 c

ATOM 697 CG PRO 50 50.043 34.518 28.375 00 0.00 c

ATOM 698 HA PRO 50 49.303 33.175 25.462 00 0.00 H

ATOM 699 1HD PRO 50 52.109 33.828 28.450 00 0.00 H

ATOM 700 2HD PRO 50 50.905 32.507 28.437 00 0.00 H

ATOM 701 1HB PRO 50 48.370 35.221 27.154 00 0.00 H

ATOM 702 2HB PRO 50 48.351 33.480 27.505 00 00 H

ATOM 703 1HG PRO 50 50.453 35.546 28.347 00 00 H

ATOM 704 2HG PRO 50 49.621 34.353 29.383 00 00 H

ATOM 705 N ILE 51 49.929 34.897 23.655 00 00 N

ATOM 706 CA ILE 51 50.136 35.939 22.601 00 00 C

ATOM 707 C ILE 51 49.049 35.841 21.469 00 00 C

ATOM 708 0 ILE 51 48.047 36.551 21.549 00 0.00 O

ATOM 709 CB ILE 51 51.660 35.983 22.187 1.00 0.00 C

ATOM 710 CGI ILE 51 52.012 37.255 21.359 1.00 0.00 C

ATOM 711 CG2 ILE 51 52.209 34.697 21.505 1.00 0.00 C

ATOM 712 CD1 ILE 51 53.508 37.479 21.055 1.00 0.00 C ATOM 713 H ILE 51 50.143 33.,905 23.,498 1.00 0.,00 H

ATOM 714 HA ILE 51 49. 928 36. .933 23. ,045 1. 00 0. ,00 H

ATOM 715 HB ILE 51 52. 223 36. ,078 23. ,140 1. 00 0. ,00 H

ATOM 716 1HG1 ILE 51 51. 450 37. ,246 20. ,404 1. 00 0. .00 H

ATOM 717 2HG1 ILE 51 51. 640 38, ,142 21, ,904 1. 00 0. ,00 H

ATOM 718 2HG2 ILE 51 51. 848 33. ,771 21. ,992 1. 00 0. ,00 H

ATOM 719 3HG2 ILE 51 51. 960 34. ,633 20. ,431 1. 00 0, .00 H

ATOM 720 1HG2 ILE 51 53. ,312 34, .651 21, ,573 1. ,00 0, ,00 H

ATOM 721 2HD1 ILE 51 54. 124 37. .450 21. .974 1. 00 0. .00 H

ATOM 722 3HD1 ILE 51 53. ,911 36, ,704 20, .376 1. ,00 0. .00 H

ATOM 723 1HD1 ILE 51 53. ,692 38. ,453 20. .567 1. ,00 0. .00 H

ATOM 724 N SER 52 49. ,195 34, ,996 20. .426 1. 00 0, ,00 N

ATOM 725 CA SER 52 48. ,345 35, .060 19. ,188 1. ,00 0. ,00 C

ATOM 726 C SER 52 46, ,792 34, .919 19. .361 1. ,00 0. ,00 C

ATOM 727 0 SER 52 46. ,063 35. .855 19. ,022 1. ,00 0, .00 O

ATOM 728 CB SER 52 48, ,928 34. .062 18. .153 1. ,00 0, .00 C

ATOM 729 OG SER 52 48, .301 34, .207 16. .875 1. .00 0, ,00 o

ATOM 730 H SER 52 50. ,074 34, .469 20, .461 1. ,00 0. .00 H

ATOM 731 HA SER 52 48. ,491 36, ,066 18, .747 1. .00 0, ,00 H

ATOM 732 1HB SER 52 50, ,018 34, .219 18, .023 1, .00 0, .00 H

ATOM 733 2HB SER 52 48, .820 33, ,016 18, .502 1. ,00 0, ,00 H

ATOM 734 HG SER 52 47. .343 34, .205 16, .995 1, ,00 0, .00 H

ATOM 735 N THR 53 46, .268 33, .790 19, .874 1. ,00 0, .00 N

ATOM 736 CA THR 53 44, .808 33 .664 20 .220 1, .00 0 .00 C

ATOM 737 C THR 53 44, ,346 34, .495 21, .482 1. ,00 0, .00 C

ATOM 738 0 THR 53 43, .171 34, .863 21, .558 1, .00 0, .00 O

ATOM 739 CB THR 53 44,

32 .152 20 .264 1, .00 0 .00 C

ATOM 740 OG1 THR 53 44. .790 31, .490 19, .064 1, ,00 0, .00 O

ATOM 741 CG2 THR 53 42, .896 31 .872 20, .358 1. .00 0, .00 C

ATOM 742 H THR 53 46, .934 33 .025 20 .012 1, .00 0 .00 H

ATOM 743 HA THR 53 44, .229 34, .096 19, .378 1, .00 0, .00 H

ATOM 744 HB THR 53 44, .925 31 .666 21, .115 1, .00 0, .00 H

ATOM 745 HG1 THR 53 44, .330 30 .647 19 .075 1, .00 0 .00 H

ATOM 746 1HG2 THR 53 42, .675 30, .791 20, .412 1, ,00 0, .00 H

ATOM 747 2HG2 THR 53 42, .444 32 .335 21, .254 1, .00 0 .00 H

ATOM 748 3HG2 THR 53 42, .350 32 .283 19 .487 1, .00 0 .00 H

ATOM 749 N VAL 54 45, .237 34 .853 22, .436 1, .00 0, .00 N

ATOM 750 CA VAL 54 44, .947 35 .899 23, .482 1, .00 0 .00 C

ATOM 751 C VAL 54 44 .710 37 .345 22 .905 1, .00 0 .00 C

ATOM 752 0 VAL 54 43, .748 37 .993 23, .315 1, .00 0, .00 O

ATOM 753 CB VAL 54 45 .956 35 .808 24 .683 1, .00 0 .00 C

ATOM 754 CGI VAL 54 45 .754 36 .878 25 .786 1, .00 0 .00 C

ATOM 755 CG2 VAL 54 45 .863 34 .445 25 .413 1 .00 0 .00 C

ATOM 756 H VAL 54 46 .193 34 .567 22 .205 1, .00 0 .00 H

ATOM 757 HA VAL 54 43 .979 35 .631 23 .929 1, .00 0 .00 H

ATOM 758 HB VAL 54 46 .983 35 .931 2 .282 1. .00 0 .00 H

ATOM 759 1HG1 VAL 54 44 .757 36 .803 26, .263 1, .00 0 .00 H

ATOM 760 2HG1 VAL 54 46 .514 36 .802 26 .585 1, .00 0 .00 H

ATOM 761 3HG1 VAL 54 45 .835 37 .904 25 .381 1 .00 0 .00 H

ATOM 762 2HG2 VAL 54 46 .196 33 .613 24, .766 1, .00 0 .00 H

ATOM 763 3HG2 VAL 54 46 .477 34 .393 26 .325 1 .00 0 .00 H

ATOM 764 1HG2 VAL 54 44 .827 34 .215 25 .727 1 .00 0 .00 H

ATOM 765 N ARG 55 45 .498 37 .832 21, .929 0, .00 0 .00 N

ATOM 766 CA ARG 55 45 .136 39 .024 21, .098 0, .00 0 .00 C

ATOM 767 C ARG 55 43 .761 38 .946 20 .334 0 .00 0 .00 C

ATOM 768 0 ARG 55 43 .054 39 .954 20, .275 0, .00 0, .00 O

ATOM 769 CB ARG 55 46 .316 39 .335 20, .132 0, .00 0 .00 C

ATOM 770 CG ARG 55 47 .611 39 .858 20 .807 0, .00 0 .00 C

ATOM 771 CD ARG 55 48. .796 39. .947 19, .834 0, ,00 0, .00 C

ATOM 772 NE ARG 55 50 .005 40, .368 20, .589 0, .00 0, .00 N

ATOM 773 CZ ARG 55 51 .093 40 .923 20, .070 0, .00 0 .00 C

ATOM 774 NH1 ARG 55 51 .248 41 .196 18, .811 0, .00 0. .00 N

ATOM 775 NH2 ARG 55 52, .056 41, .207 20. .874 0. ,00 0, .00 N

ATOM 776 H ARG 55 46 .259 37, .194 21, .658 0, .00 0, .00 H

ATOM 777 HA ARG 55 45 .029 39, .891 21, .779 0, .00 0, .00 H ATOM 778 1HB ARG 55 45.,981 40.,086 19.,388 o.,00 0.,00 H

ATOM 779 2HB ARG 55 46. ,525 38. ,428 19, ,527 o. ,00 0. ,00 H

ATOM 780 1HG ARG 55 47. ,870 39. .185 21. .650 o. ,00 0, .00 H

ATOM 781 2HG ARG 55 47. ,407 40. ,845 21. .269 o. ,00 0, .00 H

ATOM 782 1HD ARG 55 48. ,533 40, ,653 19, .017 o. ,00 0. ,00 H

ATOM 783 2HD ARG 55 48. ,962 38, ,960 19. ,349 o. ,00 0, ,00 H

ATOM 784 HE ARG 55 50. ,045 40. .243 21, .605 1, ,00 0, ,00 H

ATOM 785 1HH1 ARG 55 52, .119 41. .632 18, .502 o. .00 0, .00 H

ATOM 786 2HH1 ARG 55 50. ,447 40. .948 18, .226 o. ,00 0, .00 H

ATOM 787 1HH2 ARG 55 52. ,888 41, .639 20, .468 o, ,00 0, .00 H

ATOM 788 2HH2 ARG 55 51, ,914 40. .987 21, .861 o, .00 0. .00 H

ATOM 789 N GLU 56 43. ,347 37, .779 19, .799 o, ,00 0, .00 N

ATOM 790 CA GLU 56 41. ,969 37. .583 19, .251 o. ,00 0, .00 C

ATOM 791 C GLU 56 40, .798 37. .633 20, .303 o, ,00 0, .00 C

ATOM 792 o GLU 56 39, .805 38, .320 20 .053 o, ,00 0, .00 0

ATOM 793 CB GLU 56 41, ,966 36, .285 18 .392 o, .00 0, .00 C

ATOM 794 CG GLU 56 40, .774 36. ,146 17, .402 o, .00 0. .00 C

ATOM 795 CD GLU 56 40. .811 37. .084 16, .190 o, .00 0, .00 C

ATOM 796 OEl GLU 56 41. .825 37, .334 15 .545 o, ,00 0, .00 0

ATOM 797 OE2 GLU 56 39, .591 37, .604 15 .895 o, .00 0, .00 0

ATOM 798 H GLU 56 44. .023 37, .012 19, .852 o. .00 0. .00 H

ATOM 799 HA GLU 56 41. .777 38, .419 18 .546 o, .00 0, .00 H

ATOM 800 1HB GLU 56 41. .990 35, .405 19 .062 o, .00 0, .00 H

ATOM 801 2HB GLU 56 42, .899 36, .219 17 .797 o, .00 0, .00 H

ATOM 802 1HG GLU 56 39. ,803 36, .300 17 .908 o, .00 0, .00 H

ATOM 803 2HG GLU 56 40, .720 35, .133 16 .978 0, .00 0, .00 H

ATOM 804 N VAL 57 40, .887 36, .917 21 .450 1, .00 0, .00 N TOM 805 CA VAL 57 39, .934 37 .114 22 .599 1 .00 0 .00 C

ATOM 806 C VAL 57 40, .008 38, .538 23 .274 1, .00 0, .00 C

ATOM 807 o VAL 57 38, .971 39, .044 23 .710 1, .00 0, .00 0

ATOM 808 CB VAL 57 39, .849 35, .841 23 .504 1 .00 0, .00 C

ATOM 809 CGI VAL 57 40 .983 35 .680 24 .525 1 .00 0 .00 C

ATOM 810 CG2 VAL 57 38, .502 35, .717 24 .242 1, .00 0, .00 C

ATOM 811 H VAL 57 41, .743 36, .354 21 .511 1 .00 0 .00 H

ATOM 812 HA VAL 57 38 .936 37. .147 22 .117 1 .00 0 .00 H

ATOM 813 HB VAL 57 39 .899 34 .966 22 .827 1 .00 0 .00 H

ATOM 814 1HG1 VAL 57 41, .018 36, .517 25 .247 1, .00 0, .00 H

ATOM 815 2HG1 VAL 57 40, .902 34, .738 25 .099 1 .00 0, .00 H

ATOM 816 3HG1 VAL 57 41 .944 35 .659 23 .997 1 .00 0 .00 H

ATOM 817 2HG2 VAL 57 37 .645 35 .793 23 .549 1 .00 0 .00 H

ATOM 818 3HG2 VAL 57 38, .396 34, .744 24 .752 1, .00 0, .00 H

ATOM 819 1HG2 VAL 57 38, .367 36, .511 24 .998 1 .00 0, .00 H

ATOM 820 N ALA 58 41 .189 39, .203 23 .352 1 .00 0 .00 N

ATOM 821 CA ALA 58 41 .308 40 .620 23 .828 1 .00 0 .00 C

ATOM 822 C ALA 58 40, .508 41, .580 22 .858 1, .00 0, .00 C

ATOM 823 o ALA 58 39 .896 42, .545 23 .313 1 .00 0, .00 o

ATOM 824 CB ALA 58 42 .792 40, .966 24 .011 1 .00 0, .00 C

ATOM 825 H ALA 58 41 .992 38 .669 22 .991 1 .00 0 .00 H

ATOM 826 HA ALA 58 40, .814 40, .701 24 .816 1, .00 0, .00 H

ATOM 827 2HB ALA 58 43 .289 40, .280 24 .721 1 .00 0, .00 H

ATOM 828 3HB ALA 58 43 .336 40, .906 23 .051 1 .00 0 .00 H

ATOM 829 1HB ALA 58 42 .917 41, .995 24 .394 1 .00 0 .00 H

ATOM 830 N LEU 59 40, .530 41, .341 21, .524 0, .00 0, .00 N

ATOM 831 CA LEU 59 39 .622 42, .023 20 .543 0, .00 0, .00 C

ATOM 832 C LEU 59 38 .093 41, .895 20 .883 0, .00 0, .00 C

ATOM 833 O LEU 59 37 .329 42, .825 20 .626 0 .00 0 .00 o

ATOM 834 CB LEU 59 40, .024 41, .579 19, .109 0, .00 0, .00 C

ATOM 835 CG LEU 59 39, .361 42, .322 17, .919 0, .00 0, .00 C

ATOM 836 CD1 LEU 59 39 .738 43, .812 17, .854 0, .00 0, .00 C

ATOM 837 CD2 LEU 59 39 .766 41, .650 16 .596 0, .00 0, .00 C

ATOM 838 H LEU 59 41, .065 40. .506 21, .253 0. .00 0, .00 H

ATOM 839 HA LEU 59 39, .839 43. .105 20, .618 0. .00 0, .00 H

ATOM 840 1HB LEU 59 39, .796 40. .502 19, .004 0. .00 0, .00 H

ATOM 841 2HB LEU 59 41, .124 41. .636 18, .992 0. .00 0, .00 H

ATOM 842 HG LEU 59 38, .258 42. .233 18, ,013 0. ,00 0, .00 H ATOM 843 1HD1 LEU 59 39.273 44.300 16.978 0.00 0.00 H

ATOM 844 2HD1 LEU 59 39. 384 44. 356 18. 748 0. 00 0. 00 H

ATOM 845 3HD1 LEU 59 40. 832 43. 958 17. 779 0. 00 0. 00 H

ATOM 846 1HD2 LEU 59 39. 256 42. 100 15. 725 0. 00 0. 00 H

ATOM 847 2HD2 LEU 59 40. ,855 41. 696 16. ,406 0. 00 0. ,00 H

ATOM 848 3HD2 LEU 59 39. 495 40. 574 16. 582 0. 00 0. 00 H

ATOM 849 N LEU 60 37. ,634 40. ,742 21. ,417 0. ,00 0. ,00 N

ATOM 850 CA LEU 60 36. .279 40. ,607 22, ,037 0. ,00 0. ,00 C

ATOM 851 C LEU 60 36. ,020 41. 557 23. ,276 0. ,00 0. ,00 C

ATOM 852 0 LEU 60 34. ,860 41. ,855 23, ,567 0. ,00 0. ,00 O

ATOM 853 CB LEU 60 35. ,881 39. 110 22. ,201 0. ,00 0. ,00 C

ATOM 854 CG LEU 60 36. ,107 38. ,130 21. ,O05 0. ,00 0. ,00 C

ATOM 855 CD1 LEU 60 35, .499 36. ,752 21, ,309 0. ,00 0, .00 C

ATOM 856 CD2 LEU 60 35. .562 38. ,608 19. ,646 0. ,00 0. ,00 C

ATOM 857 H LEU 60 38, .343 40. ,004 21, ,492 0. ,00 0, .00 H

ATOM 858 HA LEU 60 35. .560 40. .994 21, .287 0, .00 0, .00 H

ATOM 859 1HB LEU 60 34, .811 39. .083 22, ,488 0. ,00 0, .00 H

ATOM 860 2HB LEU 60 36, .413 38, .709 23, ,083 0, .00 0, .00 H

ATOM 861 HG LEU 60 37, .200 38. ,000 20, ,877 0. ,00 0, ,00 H

ATOM 862 1HD1 LEU 60 35, ,755 36, ,007 20, .533 0, ,00 0, .00 H

ATOM 863 2HD1 LEU 60 35, .849 36, ,345 22, ,272 0, ,00 0, .00 H

ATOM 864 3HD1 LEU 60 34. .393 36, .788 21, ,363 0, .00 0, .00 H

ATOM 865 1HD2 LEU 60 35. .826 37, .909 18. .831 0, ,00 0, .00 H

ATOM 866 2HD2 LEU 60 34, ,464 38, .703 19. ,644 0. ,00 0, .00 H

ATOM 867 3HD2 LEU 60 35, .978 39, .588 19. .349 0. ,00 0, .00 H

ATOM 868 N ARG 61 37 .059 42, .046 24, .006 0, .00 0, .00 N

ATOM 869 CA ARG 61 36, .902 43. .090 25, .080 0. ,00 0, .00 C

ATOM 870 C ARG 61 36 .434 44, .430 24, .377 0, .00 0, .00 C

ATOM 871 0 ARG 61 35 .560 45, .118 24, .906 0, .00 0, .00 O

ATOM 872 CB ARG 61 38 .171 43. .280 25, .941 0, .00 0, .00 C

ATOM 873 CG ARG 61 38 .625 42, .058 26, .777 0, .00 0 .00 C

ATOM 874 CD ARG 61 39, .938 42, .378 27, .504 0, .00 0. .00 C

ATOM 875 NE ARG 61 40 .402 41, .214 28, .300 0, .00 0 .00 N

ATOM 876 CZ ARG 61 41 .533 41 .179 28 .995 0 .00 0 .00 C

ATOM 877 NH1 ARG 61 42 .388 42, .157 29, .058 0, .00 0 .00 N

ATOM 878 NH2 ARG 61 41 .797 40, .109 29, .651 0, .00 0 .00 N

ATOM 879 H ARG 61 37 .975 41 .739 23 .660 0 .00 0 .00 H

ATOM 880 HA ARG 61 36 .077 42, .782 25, .757 0 .00 0 .00 H

ATOM 881 1HB ARG 61 37 .959 44, .114 26 .642 0 .00 0 .00 H

ATOM 882 2HB ARG 61 38 .990 43, .650 25, .299 0 .00 0 .00 H TOM 883 1HG ARG 61 38 .728 41, .169 26, .122 0 .00 0 .00 H

ATOM 884 2HG ARG 61 37 .817 41 .806 27 .502 0 .00 0 .00 H TOM 885 1HD ARG 61 39 .762 43, .257 28, .164 0 .00 0 .00 H

ATOM 886 2HD ARG 61 40 .699 42 .687 26 .757 0 .00 0 .00 H

ATOM 887 HE ARG 61 39 .780 40 .403 28 .404 1 .00 0 .00 H

ATOM 888 1HH1 ARG 61 43 .184 42, .073 29 .685 0 .00 0 .00 H

ATOM 889 2HH1 ARG 61 42 .050 42 .996 28 .578 0 .00 0 .00 H

ATOM 890 1HH2 ARG 61 42 .609 40, .110 30, .266 0 .00 0 .00 H

ATOM 891 2HH2 ARG 61 41 .052 39 .409 29 .654 0 .00 0 .00 H TOM 892 N ARG 62 37 .032 44 .847 23 .225 1 .00 0 .00 N

ATOM 893 CA ARG 62 36 .458 45, .953 22. .397 1 .00 0 .00 C TOM 894 C ARG 62 34 .922 45 .820 22 .054 1 .00 0 .00 C

ATOM 895 0 ARG 62 34 .214 46, .827 22 .091 1 .00 0 .00 O

ATOM 896 CB ARG 62 37 .394 46 .104 21 .167 1 .00 0 .00 C

ATOM 897 CG ARG 62 37 .109 47 .309 20 .241 1 .00 0 .00 C

ATOM 898 CD ARG 62 37 .960 47, .263 18 .963 1 .00 0 .00 C

ATOM 899 ' NE ARG 62 37 .623 48, .444 18 .130 1 .00 0 .00 N

ATOM 900 CZ ARG 62 38 .119 48 .706 16 .928 1 .00 0 .00 C TOM 901 NH1 ARG 62 38 .989 47, .960 16 .313 1 .00 0 .00 N

ATOM 902 NH2 ARG 62 37 .709 49 .773 16 .338 1 .00 0 .00 N

ATOM 903 H ARG 62 37 .654 44, .130 22 .836 1 .00 0, .00 H

ATOM 904 HA ARG 62 36 .538 46, .882 22 .996 1 .00 0 .00 H

ATOM 905 1HB ARG 62 38 .449 46 .153 21 .504 1 .00 0 .00 H

ATOM 906 2HB ARG 62 37 .321 45, .182 20 .564 1. .00 0, .00 H

ATOM 907 1HG ARG 62 36 .031 47, .316 19 .972 1 .00 0 .00 H ATOM 908 2HG ARG 62 37.273 48.251 20.804 00 00 H

ATOM 909 1HD ARG 62 39.038 47.246 19.226 00 00 H

ATOM 910 2HD ARG 62 37.745 46.317 18.418 00 00 H

ATOM 911 HE ARG 62 36.911 49.111 18.448 00 00 H

ATOM 912 2HH1 ARG 62 39.219 47.102 16.818 00 00 H

ATOM 913 1HH1 ARG 62 39.266 48.219 15.366 00 00 H

ATOM 914 1HH2 ARG 62 36.990 50.309 16.830 00 00 H

ATOM 915 2HH2 ARG 62 38.052 49.955 15.395 00 00 H

ATOM 916 N LEU 63 34.391 44.605 21.810 00 00 N

ATOM 917 CA LEU 63 32.920 44.349 21.775 00 00 c

ATOM 918 C LEU 63 32.137 44.583 23.118 0.00 00 c

ATOM 919 0 LEU 63 31.054 45.172 23.056 0.00 00 o

ATOM 920 CB LEU 63 32.625 42.933 21.211 00 0.00 c

ATOM 921 CG LEU 63 33.161 42.545 19.807 00 0.00 c

ATOM 922 CD1 LEU 63 32.771 41.091 19.518 00 0.00 c

ATOM 923 CD2 LEU 63 32.631 43.434 18.671 0.00 0.00 c

ATOM 924 H LEU 63 35.062 43.835 21.893 0.00 0.00 H

ATOM 925 HA LEU 63 32.476 45.061 21.056 00 00 H

ATOM 926 1HB LEU 63 31.526 42.796 21.204 00 00 H

ATOM 927 2HB LEU 63 32.979 42.189 21.949 00 00 H

ATOM 928 HG LEU 63 34.268 42.613 19.816 00 00 H

ATOM 929 1HD1 LEU 63 33.181 40.731 18.558 00 0.00 H

ATOM 930 2HD1 LEU 63 33.145 40.414 20.307 00 0.00 H

ATOM 931 3HD1 LEU 63 31.673 40.956 19.476 00 00 H

ATOM 932 1HD2 LEU 63 33.031 43.123 17.688 00 00 H

ATOM 933 2HD2 LEU 63 31.529 43.403 18.591 0.00 00 H

ATOM 934 3HD2 LEU 63 32.915 44.494 18.805 0.00 00 H

ATOM 935 N GLU 64 32.642 44.177 24.316 00 00 N

ATOM 936 CA GLU 64 32.017 44.583 25.623 00 0.00 c

ATOM 937 C GLU 64 31.889 46.127 25.880 00 0.00 c

ATOM 938 0 GLU 64 30.845 46.561 26.366 00 00 0

ATOM 939 CB GLU 64 32.576 43.812 26.861 00 00 c

ATOM 940 CG GLU 64 33.851 44.359 27.569 00 00 c

ATOM 941 CD GLU 64 34.150 43.767 28.945 00 00 c

ATOM 942 OE1 GLU 64 33.464 43.971 29.939 00 00 0

ATOM 943 OE2 GLU 64 35.298 43.035 28.960 00 00 0

ATOM 944 H GLU 64 33.560 43.724 24.275 00 00 H

ATOM 945 HA GLU 64 30.966 44.240 25.550 00 00 H

ATOM 946 1HB GLU 64 32.727 42.745 26.606 00 00 H

ATOM 947 2HB GLU 64 31.768 43.793 27.615 00 00 H

ATOM 948 1HG GLU 64 33.782 45.445 27.741 00 00 H

ATOM 949 2HG GLU 64 34.739 44.208 26.946 00 00 H

ATOM 950 N ALA 65 32.914 46.935 25.534 00 00 N

ATOM 951 CA ALA 65 32.862 48.424 25.605 00 00 c

ATOM 952 C ALA 65 31.664 49.178 24.919 00 00 c

ATOM 953 0 ALA 65 31.205 50.193 25.448 00 00 0

ATOM 954 CB ALA 65 34.230 48.884 25.065 00 00 c

ATOM 955 H ALA 65 33.715 46.415 25.163 00 00 H

ATOM 956 HA ALA 65 32.789 48.702 26.677 00 00 H

ATOM 957 2HB ALA 65 35.071 48.430 25.620 00 00 H

ATOM 958 3HB ALA 65 34.352 48.639 23.994 00 00 H

ATOM 959 1HB ALA 65 34.335 49.980 25.163 00 00 H

ATOM 960 N PHE 66 31.136 48.661 23.798 00 00 N

ATOM 961 CA PHE 66 29.824 49.092 23.229 00 00 C

ATOM 962 C PHE 66 28.532 48.734 24.059 00 0.00 C

ATOM 963 0 PHE 66 27.579 49.513 24.045 00 0.00 0

ATOM 964 CB PHE 66 29.690 48.469 21.808 00 0.00 C

ATOM 965 CG PHE 66 30.688 48.917 20.727 00 o.oo C

ATOM 966 GDI PHE 66 31.784 48.111 20.403 00 0.00 C

ATOM 967 CE1 PHE 66 32.657 48.482 19.383 00 00 C

ATOM 968 CZ PHE 66 32.439 49.663 18.680 00 00 C

ATOM 969 CE2 PHE 66 31.352 50.476 18.998 00 00 C

ATOM 970 CD2 PHE 66 30.478 50.103 20.018 00 00 C

ATOM 971 H PHE 66 31.562 47.761 23.558 00 00 H

ATOM 972 HA PHE 66 29.822 50.196 23.137 0.00 00 H ATOM 973 1HB PHE 66 28.670 48.676 21.428 ,00 00 H

ATOM 974 2HB PHE 66 29.700 47.366 21.906 ,00 00 H

ATOM 975 HD1 PHE 66 31.950 47.198 20.950 ,00 00 H

ATOM 976 HE1 PHE 66 33.489 47.840 19.134 .00 00 H

ATOM 977 HZ PHE 66 33.102 49.944 17.876 .00 00 H

ATOM 978 HE2 PHE 66 31.176 51.391 18.452 .00 00 H

ATOM 979 HD2 PHE 66 29.632 50.733 20.256 .00 00 H

ATOM 980 N GLU 67 28.462 47.540 24.689 .00 00 N

ATOM 981 CA GLU 67 27.225 47.005 25.349 0.00 00 c

ATOM 982 c GLU 67 26.017 46.715 24.373 0.00 00 c

ATOM 983 0 GLU 67 24.939 47.304 24.495 00 00 0

ATOM 984 CB GLU 67 26.796 47.798 26.627 .00 00 c

ATOM 985 CG GLU 67 27.829 47.988 27.774 .00 00 c

ATOM 986 CD GLU 67 28.656 49.270 27.674 .00 00 c

ATOM 987 OE1 GLU 67 28.174 50.397 27.648 0.00 00 o

ATOM 988 OE2 GLU 67 29.988 49.029 27.621 0.00 0.00 0

ATOM 989 H GLU 67 29.395 47.196 24.949 0.00 0.00 H

ATOM 990 HA GLU 67 27.518 46.011 25.734 0.00 .00 H

ATOM 991 1HB GLU 67 25.916 47.285 27.058 .00 .00 H

ATOM 992 2HB GLU 67 26.397 48.787 26.322 .00 ,00 H

ATOM 993 1HG GLU 67 28.524 47.134 27.842 ,00 .00 H

ATOM 994 2HG GLU 67 27.314 48.064 28.742 .00 .00 H

ATOM 995 N HIS 68 26.178 45.784 23.411 0.00 ,00 N

ATOM 996 CA HIS 68 25.095 45.426 22.446 0.00 .00 c

ATOM 997 C HIS 68 24.167 44.275 23.006 00 0.00 c

ATOM 998 O HIS 68 24.708 43.220 23.360 00 0.00 o

ATOM 999 CB HIS 68 25.761 45.064 21.094 00 00 c

ATOM 1000 CG HIS 68 24.796 45.026 19.911 00 00 c

ATOM 1001 ND1 HIS 68 24.011 43.929 19.583 0.00 00 N

ATOM 1002 CE1 HIS 68 23.388 44.435 18.472 0.00 00 c

ATOM 1003 NE2 HIS 68 23.640 45.715 18.065 .00 00 N

ATOM 1004 CD2 HIS 68 24.580 46.082 19.010 .00 00 c

ATOM 1005 H HIS 68 27.122 45.387 23.387 .00 00 H

ATOM 1006 HA HIS 68 24.493 46.338 22.267 .00 00 H

ATOM 1007 1HB HIS 68 26.287 44.095 21.175 .00 00 H

ATOM 1008 2HB HIS 68 26.562 45.792 20.859 .00 00 H

ATOM 1009 HE1 HIS 68 22.716 43.805 17.908 .00 0.00 H

ATOM 1010 HE2 HIS 68 23.400 46.184 17.185 .00 0.00 H

ATOM 1011 HD2 HIS 68 25.099 47.031 19.046 .00 00 H

ATOM 1012 N PRO 69 22.807 44.394 23.105 o.oo 00 N

ATOM 1013 CA PRO 69 21.947 43.342 23.738 o.oo 00 c

ATOM 1014 CD PRO 69 22.052 45.577 22.646 o.oo 00 c

ATOM 1015 C PRO 69 21.769 41.957 23.023 o.oo 00 c

ATOM 1016 O PRO 69 21.386 40.988 23.679 o.oo 00 o

ATOM 1017 CB PRO 69 20.613 44.104 23.897 o.oo 00 c

ATOM 1018 CG PRO 69 20.595 45.135 22.766 o.oo 00 c

ATOM 1019 HA PRO 69 22.340 43.116 24.748 o.oo 00 H

ATOM 1020 1HD PRO 69 22.302 45.876 21.609 o.oo 00 H

ATOM 1021 2HD PRO 69 22.262 46.446 23.305 .oo 0.00 H

ATOM 1022 1HB PRO 69 20.599 44.626 24.875 ,oo 0.00 H

ATOM 1023 2HB PRO 69 19.721 43.447 23.894 .oo .00 H

ATOM 1024 1HG PRO 69 19.915 45.983 22.975 .oo .00 H

ATOM 1025 2HG PRO 69 20.254 44.667 21.825 .oo .00 H

ATOM 1026 N ASN 70 22.008 41.865 21.705 .oo .00 N

ATOM 1027 CA ASN 70 21.817 40.605 20.915 .oo .00 C

ATOM 1028 C ASN 70 23.045 39.612 20.824 .oo ,00 C

ATOM 1029 O ASN 70 22.902 38.505 20.294 .oo ,00 0

ATOM 1030 CB ASN 70 21.327 41.027 19.504 .oo .00 C

ATOM 1031 CG ASN 70 19.930 41.646 19.412 .oo ,00 C

ATOM 1032 OD1 ASN 70 18.914 40.972 19.340 .oo .00 O

ATOM 1033 ND2 ASN 70 19.814 42.948 19.418 .oo .00 N

ATOM 1034 H ASN 70 22.464 42.709 21.338 .oo .00 H

ATOM 1035 HA ASN 70 21.006 40.004 21.372 .oo .00 H

ATOM 1036 1HB ASN 70 21.287 40.127 18.862 .00 .00 H

ATOM 1037 2HB ASN 70 22.076 41.679 19.021 .oo .00 H ATOM 1038 1HD2 ASN 70 20.670 43.424 19.,718 0.,00 0.00 H

ATOM 1039 2HD2 ASN 70 18. ,858 43. ,249 19. ,616 0. ,00 0. ,00 H

ATOM 1040 N VAL 71 24. 237 39. ,981 21. ,318 1. ,00 0. 00 N

ATOM 1041 CA VAL 71 25. ,389 39. ,047 21. ,543 1. ,00 0. ,00 C

ATOM 1042 C VAL 71 25. ,550 38. ,754 23. ,074 1. ,00 0. ,00 C

ATOM 1043 o VAL 71 25, ,256 39. ,620 23. ,908 1. ,00 0. ,00 O

ATOM 1044 CB VAL 71 26. ,723 39. .595 20, ,918 1. ,00 0. .00 C

ATOM 1045 CGI VAL 71 26. ,694 39. ,659 19. ,376 1, .00 0. ,00 C

ATOM 1046 CG2 VAL 71 27. ,196 40. ,966 21, .459 1, .00 0. .00 C

ATOM 1047 H VAL 71 24. ,217 40. ,907 21. ,764 1. .00 0. .00 H

ATOM 1048 HA VAL 71 25, .191 38, .074 21, .053 1, .00 0. ,00 H

ATOM 1049 HB VAL 71 27, ,516 38, .863 21, .175 1, .00 0. ,00 H

ATOM 1050 1HG1 VAL 71 25, .977 40. .416 19, .007 1, .00 0. ,00 H

ATOM 1051 2HG1 VAL 71 27, ,682 39, ,925 18, .955 1, .00 0. ,00 H

ATOM 1052 3HG1 VAL 71 26, ,408 38. .693 18. ,922 1. .00 0. ,00 H

ATOM 1053 2HG2 VAL 71 27, ,304 40, .965 22, .559 1, .00 0, .00 H

ATOM 1054 3HG2 VAL 71 28, .181 41. .249 21, ,048 1, .00 0, .00 H

ATOM 1055 1HG2 VAL 71 26, .488 41, .779 21. ,208 1, .00 0. .00 H

ATOM 1056 N VAL 72 26, .071 37, .576 23, .477 0, .00 0, .00 N

ATOM 1057 CA VAL 72 26, .460 37, .341 24, ,905 0, .00 0, .00 C

ATOM 1058 C VAL 72 27, .702 38, .210 25, ,304 0, .00 0, .00 C

ATOM 1059 o VAL 72 28 .733 38, .198 24, .619 0, .00 0, .00 O

ATOM 1060 CB VAL 72 26, .612 35, .813 25, ,239 0, .00 0, .00 C

ATOM 1061 CGI VAL 72 27 .949 35, .166 24, .817 0, .00 0, .00 C

ATOM 1062 CG2 VAL 72 26, .415 35, ,525 26. .746 0, .00 0, .00 C

ATOM 1063 H VAL 72 26, .326 36, .913 22, ,730 0, .00 0, .00 H

ATOM 1064 HA VAL 72 25 .598 37, .682 25, .510 0 , .00 0 .00 H

ATOM 1065 HB VAL 72 25, .811 35, .262 24. ,704 0, .00 0, .00 H

ATOM 1066 1HG1 VAL 72 27 .945 34, .070 24, .966 0, .00 0, .00 H

ATOM 1067 2HG1 VAL 72 28. .170 35, .352 23. .752 0, .00 0, .00 H

ATOM 1068 3HG1 VAL 72 28 .805 35, .567 25. .387 0, .00 0, .00 H

ATOM 1069 1HG2 VAL 72 26 .469 34, .443 26, .973 0 .00 0 .00 H

ATOM 1070 2HG2 VAL 72 27 .179 36, .015 27, ,381 0, .00 0, .00 H

ATOM 1071 3HG2 VAL 72 25 .427 35, .855 27, .117 0, .00 0, .00 H

ATOM 1072 N ARG 73 27, .627 38, .868 26, ,457 1, .00 0, .00 N

ATOM 1073 CA ARG 73 28 .732 39, .728 26, .904 1, .00 0, .00 C

ATOM 1074 C ARG 73 29 .924 39 .022 27 .626 1 .00 0 .00 C

ATOM 1075 o ARG 73 29 .774 38, .534 28, .753 1, .00 0, .00 O

ATOM 1076 CB ARG 73 28 .134 40, .848 27, .809 1 .00 0 .00 C

ATOM 1077 CG ARG 73 29 .160 41, .914 28, ,286 1, .00 0, .00 C

ATOM 1078 CD ARG 73 28 .610 42 .899 29, .324 1 .00 0 .00 C

ATOM 1079 NE ARG 73 29 .763 43 .711 29 .789 1 .00 0 .00 N

ATOM 1080 CZ ARG 73 29 .716 44, .712 30, .653 1, .00 0. .00 C

ATOM 1081 NH1 ARG 73 28 .627 45 .143 31, .214 1 .00 0 .00 N

ATOM 1082 NH2 ARG 73 30 .827 45, .286 30, .952 1, .00 0 .00 N

ATOM 1083 H ARG 73 26 .804 38 .687 27, .034 1 .00 0 .00 H

ATOM 1084 HA ARG 73 29 .143 40 .267 26 .024 1 .00 0 .00 H

ATOM 1085 1HB ARG 73 27 .306 41 .367 27, .287 1, .00 0 .00 H

ATOM 1086 2HB ARG 73 27 .663 40 .385 28, .700 1 .00 0 .00 H

ATOM 1087 1HG ARG 73 30 .042 41, .404 28, ,729 1, .00 0 .00 H

ATOM 1088 2HG ARG 73 29 .560 42 .469 27, .412 1 .00 0 .00 H

ATOM 1089 1HD ARG 73 27 .814 43 .529 28, .871 1 .00 0 .00 H

ATOM 1090 2HD ARG 73 28 .137 42 .345 30, .166 1, .00 0 .00 H

ATOM 1091 HE ARG 73 30 .727 43 .527 29, .474 1 .00 0 .00 H

ATOM 1092 2HH1 ARG 73 27 .787 44, .657 30. .893 1, .00 0 .00 H

ATOM 1093 1HH1 ARG 73 28 .690 45 .973 31, .801 1, .00 0 .00 H

ATOM 1094 1HH2 ARG 73 31 .680 44 .899 30, .506 1 .00 0 .00 H

ATOM 1095 2HH2 ARG 73 30 .801 46, .102 31, ,559 1, .00 0 .00 H

ATOM 1096 N LEU 74 31 .083 38, .890 26, .949 0, .00 0 .00 N

ATOM 1097 CA LEU 74 32 .334 38, .542 27. .675 0, .00 0, .00 C

ATOM 1098 C LEU 74 32 .727 39, .685 28. .675 0, .00 0. .00 C

ATOM 1099 O LEU 74 33 .116 40, .782 28. .267 0, .00 0 .00 O

ATOM 1100 CB LEU 74 33, .419 38, .260 26. .596 0, .00 0, .00 C

ATOM 1101 CG LEU 74 34 .824 37, .845 27. .110 0, .00 0, .00 C

ATOM 1102 CD1 LEU 74 34, .842 36. .457 27. ,769 0. .00 0, .00 C ATOM 1103 CD2 LEU 74 35.,834 37..863 25..954 0..00 0,.00 C

ATOM 1104 H LEU 74 31, .088 39. .328 26. .023 0, ,00 0. .00 H

ATOM 1105 HA LEU 74 32. ,174 37, .601 28, .238 0. ,00 0. .00 H

ATOM 1106 1HB LEU 74 33. .531 39, .180 25. .986 0, .00 0. .00 H

ATOM 1107 2HB LEU 74 33. .051 37. .493 25, .888 0. .00 0, .00 H

ATOM 1108 HG LEU 74 35. ,157 38. .595 27, .860 0. .00 0, .00 H

ATOM 1109 1HD1 LEU 74 35. .837 36. .209 28, .178 0, .00 0, .00 H

ATOM 1110 2HD1 LEU 74 34. .139 36, .403 28, .623 0, .00 0, .00 H

ATOM llll 3HD1 LEU 74 34. .555 35, .655 27. .066 0, .00 0. .00 H

ATOM 1112 1HD2 LEU 74 36. .856 37, .643 26, .305 0, .00 0, .00 H

ATOM 1113 2HD2 LEU 74 35. .581 37. .133 25, .163 0, .00 0, .00 H

ATOM 1114 3HD2 LEU 74 35. .875 38. .861 25. .477 0, ,00 0. .00 H

ATOM 1115 N MET 75 32. .614 39. .417 29, .981 1, .00 0, .00 N

ATOM 1116 CA MET 75 32. .982 40, .393 31, .047 1, .00 0, .00 C

ATOM 1117 C MET 75 34. .533 40. .475 31, .289 1. ,00 0, .00 C

ATOM 1118 O MET 75 35. .119 41, .561 31, .238 1, .00 0, .00 O

ATOM 1119 CB MET 75 32. .186 40, .019 32, .336 1, .00 0, .00 C

ATOM 1120 CG MET 75 30. .672 40, .332 32, .321 1, .00 0, .00 C

ATOM 1121 SD MET 75 29. .925 39, .768 33, .863 1, .00 0, .00 S

ATOM 1122 CE MET 75 28, .205 40 .222 33, .583 1, .00 0 .00 C

ATOM 1123 H MET 75 32, .315 38 .465 30 .220 1 .00 0 .00 H

ATOM 1124 HA MET 75 32, .682 41, .417 30, .744 1, .00 0 .00 H

ATOM 1125 1HB MET 75 32, .347 38 .954 32 .592 1 .00 0 .00 H

ATOM 1126 2HB MET 75 32, .631 40 .568 33 .191 1 .00 0 .00 H

ATOM 1127 1HG MET 75 30, .492 41, .415 32, .194 1, .00 0 .00 H

ATOM 1128 2HG MET 75 30, .173 39 .824 31 .474 1 .00 0 .00 H

ATOM 1129 1HE MET 75 28 .065 41 -312 33 .697 1 .00 0 ,00 H

ATOM 1130 3HE MET 75 27, .878 39, .940 32 .566 1 .00 0 .00 H

ATOM 1131 2HE MET 75 27, .547 39 .709 34 .306 1 .00 0 .00 H

ATOM 1132 N ASP 76 35 .205 39 .332 31 .512 0 .00 0 .00 N

ATOM 1133 CA ASP 76 36, .650 39, .311 31 .840 0, .00 0 .00 C

ATOM 1134 C ASP 76 37, .386 37 .988 31 .465 0 .00 0 .00 C

ATOM 1135 O ASP 76 36 .861 36 .885 31 .629 0 .00 0 .00 O

ATOM 1136 CB ASP 76 36, .818 39, .427 33 .394 0, .00 0 .00 C

ATOM 1137 CG ASP 76 36, .471 40 .756 34 .051 0 .00 0 .00 C

ATOM 1138 ODl ASP 76 37 .271 41 .674 34 .192 0 .00 0 .00 O

ATOM 1139 OD2 ASP 76 35, .187 40 .796 34, .495 0 .00 0. .00 O

ATOM 1140 H ASP 76 34, .593 38 .513 31 .566 0 .00 0 .00 H

ATOM 1141 HA ASP 76 37 .160 40 .171 31 .358 0 .00 0 .00 H

ATOM 1142 1HB ASP 76 37 .866 39 .235 33 .686 0 .00 0 .00 H

ATOM 1143 2HB ASP 76 36, .234 38 .636 33 .903 0 .00 0 .00 H

ATOM 1144 N VAL 77 38 .603 38 .098 30 .921 0 .00 0 .00 N

ATOM 1145 CA VAL 77 39 .492 36 .904 30 .763 0 .00 0 .00 C

ATOM 1146 C VAL 77 40 .535 37 .018 31 .926 0 .00 0 .00 C

ATOM 1147 O VAL 77 41 .489 37 .800 31 .853 0 .00 0 .00 O

ATOM 1148 CB VAL 77 40 .101 36 .805 29 .321 0 .00 0 .00 C

ATOM 1149 CGI VAL 77 40 .987 35 .554 29 .148 0 .00 0 .00 C

ATOM 1150 CG2 VAL 77 39 .042 36 .778 28 .195 0 .00 0 .00 c

ATOM 1151 H VAL 77 38 .910 39 .073 30 .947 0 .00 0 .00 H

ATOM 1152 HA VAL 77 38, .919 35 .964 30. .904 0 .00 0 .00 H

ATOM 1153 HB VAL 77 40 .741 37 .684 29, .143 0 .00 0 .00 H

ATOM 1154 1HG1 VAL 77 41 .399 35 .465 28 .124 0 .00 0 .00 H

ATOM 1155 2HG1 VAL 77 41, .849 35, .561 29, .840 0 .00 0 .00 H

ATOM 1156 3HG1 VAL 77 40. .421 34 .626 29, .356 0 .00 0 .00 H

ATOM 1157 1HG2 VAL 77 39 .479 36 .654 27 .187 0 .00 0 .00 H

ATOM 1158 2HG2 VAL 77 38. .311 35, .961 28. .344 0 .00 0 .00 H

ATOM 1159 3HG2 VAL 77 38 .444 37 .709 28, .168 0 .00 0 .00 H

ATOM 1160 N CYS 78 40 .329 36 .266 33, .020 0 .00 0 .00 N

ATOM 1161 CA CYS 78 41 .214 36 .324 34 .211 0 .00 0 .00 C

ATOM 1162 C CYS 78 42, .581 35, .576 34, .056 0. .00 0, .00 C

ATOM 1163 O CYS 78 42, .613 34, .363 33, .813 0 .00 0, .00 O

ATOM 1164 CB CYS 78 40 .375 35. .782 35, .388 0 .00 0, .00 C

ATOM 1165 SG CYS 78 38, .844 36, .753 35. .633 0, .00 0, ,00 S

ATOM 1166 H CYS 78 39, .468 35, .705 32. .999 0, .00 0, .00 H

ATOM 1167 HA CYS 78 41, .412 37, .391 34. .444 0, .00 0, .00 H ATOM 1168 1HB CYS 78 40.955 35.820 36.327 0.00 0.00 H

ATOM 1169 2HB CYS 78 40.103 34.719 35.235 0.00 0.00 H

ATOM 1170 HG CYS 78 39.401 37.933 35.895 00 0.00 H

ATOM 1171 N ALA 79 43.707 36.293 34.228 00 0.00 N

ATOM 1172 CA ALA 79 45.066 35.694 34.138 00 00 C

ATOM 1173 C ALA 79 45.483 34.899 35.425 00 00 c

ATOM 1174 O ALA. 79 46.115 35.427 36.344 00 00 O

ATOM 1175 CB ALA 79 46.022 36.851 33.786 1.00 00 c

ATOM 1176 H ALA 79 43.545 37.286 34.415 00 00 H

ATOM 1177 HA ALA 79 45.098 34.990 33.280 00 00 H

ATOM 1178 2HB ALA 79 45.731 37.352 32.844 00 00 H

ATOM 1179 3HB ALA 79 46.048 37.616 34.586 00 00 H

ATOM 1180 1HB ALA 79 47.054 36.479 33.655 00 0.00 H

ATOM 1181 N THR 80 45.107 33.612 35.468 00 0.00 N

ATOM 1182 CA THR 80 45.279 32.754 36.683 00 00 c

ATOM 1183 C THR 80 46.749 32.254 36.929 00 00 c

ATOM 1184 o THR 80 47.253 32.392 38.046 00 00 o

ATOM 1185 CB THR 80 44.251 31.571 36.641 00 00 c

ATOM 1186 OG1 THR 80 42.949 31.996 36.241 00 0.00 O

ATOM 1187 CG2 THR 80 44.047 30.886 38.002 00 0.00 c

ATOM 1188 H THR 80 44.377 33.394 34.778 00 ,00 H

ATOM 1189 HA THR 80 45.015 33.370 37.567 00 ,00 H

ATOM 1190 HB THR 80 44.607 30.823 35.903 00 ,00 H

ATOM 1191 HG1 THR 80 42.387 31.221 36.188 00 ,00 H

ATOM 1192 1HG2 THR 80 43.321 30.057 37.947 00 0.00 H

ATOM 1193 2HG2 THR 80 44.993 30.466 38.395 1.00 0.00 H

ATOM 1194 3HG2 THR 80 43.676 31.596 38.765 00 00 w

ATOM 1195 N SER 81 47.419 31.656 35.923 00 00 N

ATOM 1196 CA SER 81 48.816 31.148 36.051 00 00 c

ATOM 1197 C SER 81 49.742 31.772 34.955 00 00 c

ATOM 1198 O SER 81 49.746 31.348 33.794 0.00 00 O

ATOM 1199 CB SER 81 48.765 29.601 36.006 0.00 00 c

ATOM 1200 OG SER 81 50.060 29.046 36.250 00 00 O

ATOM 1201 H SER 81 46.918 31.657 35.029 00 00 H

ATOM 1202 HA SER 81 49.243 31.403 37.043 00 00 H

ATOM 1203 1HB SER 81 48.388 29.251 35.024 00 00 H

ATOM 1204 2HB SER 81 48.059 29.219 36.769 00 00 H

ATOM 1205 HG SER 81 50.008 28.083 36.234 00 00 H

ATOM 1206 N ARG 82 50.528 32.795 35.325 00 00 KΓ

ATOM 1207 CA ARG 82 51.458 33.485 34.387 0.00 00 c

ATOM 1208 C ARG 82 52.849 32.760 34.324 0.00 00 c

ATOM 1209 o ARG 82 53.619 32.784 35.288 .00 00 o

ATOM 1210 CB ARG 82 51.528 34.967 34.840 ,00 0.00 c

ATOM 1211 CG ARG 82 52.190 35.929 33.821 ,00 0.00 c

ATOM 1212 CD ARG 82 52.173 37.408 34.263 .00 0.00 c

ATOM 1213 NE ARG 82 50.805 37.998 34.269 .00 0.00 KΓ

ATOM 1214 CZ ARG 82 50.186 38.562 33.239 .00 0.00 c

ATOM 1215 NH1 ARG 82 50.690 38.665 32.045 .00 00 KΓ

ATOM 1216 NH2 ARG 82 49.009 39.035 33.446 .00 00 KΓ

ATOM 1217 H ARG 82 50.495 33.008 36.328 0.00 00 H

ATOM 1218 HA ARG 82 51.010 33.483 33.372 0.00 00 H

ATOM 1219 1HB ARG 82 52.059 35.026 35.814 .00 00 H

ATOM 1220 2HB ARG 82 50.502 35.329 35.050 .00 00 H

ATOM 1221 1HG ARG 82 51.723 35.814 32.823 .00 0.00 H

ATOM 1222 2HG ARG 82 53.245 35.614 33.676 .00 0.00 H

ATOM 1223 1HD ARG 82 52.878 37.999 33.640 ,00 00 H

ATOM 1224 2HD ARG 82 52.617 37.485 35.279 .00 00 H

ATOM 1225 HE ARG 82 50.256 37.994 35.136 .00 00 H

ATOM 1226 1HH1 ARG 82 50.151 39.132 31.316 .00 00 H

ATOM 1227 2HH1 ARG 82 51.632 38.272 31.967 .00 00 H

ATOM 1228 1HH2 ARG 82 48.544 39.496 32.664 .00 00 H

ATOM 1229 2HH2 ARG 82 48.656 38.957 34.403 .00 00 H

ATOM 1230 N THR 83 53.133 32.074 33.207 .00 00 N

ATOM 1231 CA THR 83 54.396 31.290 33.017 .00 00 c

ATOM 1232 C THR 83 55.057 31.581 31.631 ,00 00 c ATOM 1233 o THR 83 54.402 31.948 30.653 00 00 0

ATOM 1234 CB THR 83 54.158 29.751 33.202 00 00 c

ATOM 1235 OG1 THR 83 53.067 29.290 32.414 00 00 0

ATOM 1236 CG2 THR 83 53.895 29.324 34.654 0.00 00 c

ATOM 1237 H THR 83 52.413 32.095 32.480 0.00 00 H

ATOM 1238 HA THR 83 55.145 31.599 33.776 0.00 00 H

ATOM 1239 HB THR 83 55.068 29.203 32.881 0.00 00 H

ATOM 1240 HG1 THR 83 52.293 29.730 32.775 0.00 00 H

ATOM 1241 1HG2 THR 83 53.753 28.228 34.728 0.00 00 H

ATOM 1242 2HG2 THR 83 54.738 29.585 35.321 0.00 00 H

ATOM 1243 3HG2 THR 83 52.986 29.793 35.074 0.00 00 H

ATOM 1244 N ASP 84 56.372 31.324 31.528 00 00 N

ATOM 1245 CA ASP 84 57.110 31.346 30.220 00 00 c

ATOM 1246 C ASP 84 56.740 30.253 29.137 00 00 c

ATOM 1247 o ASP 84 57.273 30.305 28.028 00 00 0

ATOM 1248 CB ASP 84 58.632 31.244 30.539 00 00 c

ATOM 1249 CG ASP 84 59.232 32.366 31.386 0.00 00 c

ATOM 1250 ODl ASP 84 59.266 32.348 32.611 0.00 00 0

ATOM 1251 OD2 ASP 84 59.709 33.393 30.636 ,00 00 0

ATOM 1252 H ASP 84 56.897 31.210 32.404 ,00 0.00 H

ATOM 1253 HA ASP 84 56.940 32.328 29.735 0.00 0.00 H

ATOM 1254 1HB ASP 84 59.214 31.213 29.600 0.00 0.00 H

ATOM 1255 2HB ASP 84 58.859 30.288 31.044 00 0.00 H

ATOM 1256 N ARG 85 55.760 29.377 29.347 00 0.00 N

ATOM 1257 CA ARG 85 55.513 28.245 28.422 00 0.00 c

ATOM 1258 c ARG 85 54.125 27.579 28.440 00 0.00 c

ATOM 1259 O ARG 85 53.828 27.046 27.362 00 0.00 0

ATOM 1260 CB ARG 85 56.478 27.102 28.971 00 00 c

ATOM 1261 CG ARG 85 56.493 25.679 28.313 00 00 C

ATOM 1262 CD ARG 85 56.717 24.497 29.288 00 00 c

ATOM 1263 NE ARG 85 56.447 23.241 28.538 00 00 N

ATOM 1264 CZ ARG 85 56.098 22.065 29.045 00 00 c

ATOM 1265 NH1 ARG 85 56.016 21.800 30.313 00 00 N

ATOM 1266 NH2 ARG 85 55.818 21.127 28.210 00 0.00 N

ATOM 1267 H ARG 85 55.305 29.504 30.256 00 0.00 H

ATOM 1268 HA ARG 85 55.763 28.504 27.373 00 ,00 H

ATOM 1269 1HB ARG 85 57.521 27.482 28.963 00 ,00 H

ATOM 1270 2HB ARG 85 56.267 26.974 30.054 00 ,00 H

ATOM 1271 1HG ARG 85 55.547 25.500 27.770 00 .00 H

ATOM 1272 2HG ARG 85 57.260 25.675 27.515 00 ,00 H

ATOM 1273 1HD ARG 85 57.749 24.519 29.698 00 .00 H

ATOM 1274 2HD ARG 85 56.032 24.611 30.156 00 .00 H

ATOM 1275 HE ARG 85 56.392 23.257 27.518 00 .00 H

ATOM 1276 2HH1 ARG 85 56.198 22.603 30.922 00 .00 H

ATOM 1277 1HH1 ARG 85 55.693 20.878 30.607 00 0.00 H

ATOM 1278 1HH2 ARG 85 55.842 21.377 27.221 00 0.00 H

ATOM 1279 2HH2 ARG 85 55.512 20.234 28.600 00 00 H

ATOM 1280 N GLU 86 53.172 27.766 29.398 0.00 00 N

ATOM 1281 CA GLU 86 52.162 26.638 29.483 0.00 00 C

ATOM 1282 C GLU 86 50.609 26.795 29.169 00 00 C

ATOM 1283 O GLU 86 50.272 27.304 28.099 00 00 O

ATOM 1284 CB GLU 86 52.568 25.680 30.646 00 00 C

ATOM 1285 CG GLU 86 52.454 26.215 32.096 00 00 C

ATOM 1286 CD GLU 86 52.461 25.156 33.198 00 00 C

ATOM 1287 OE1 GLU 86 52.162 23.979 33.027 00 00 O

ATOM 1288 OE2 GLU 86 52.814 25.690 34.401 00 00 0

ATOM 1289 H GLU 86 53.488 28.260 30.239 00 00 H

ATOM 1290 HA GLU 86 52.329 25.927 28.648 00 00 H

ATOM 1291 1HB GLU 86 53.600 25.313 30.488 00 00 H

ATOM 1292 2HB GLU 86 51.953 24.762 30.561 00 00 H

ATOM 1293 1HG GLU 86 51.551 26.822 32.253 00 00 H

ATOM 1294 2HG GLU 86 53.302 26.883 32.314 00 00 H

ATOM 1295 N ILE 87 49.627 26.542 30.081 00 00 N

ATOM 1296 CA ILE 87 48.210 26.227 29.643 00 00 C

ATOM 1297 C ILE 87 46.877 26.837 30.258 00 00 C ATOM 1298 O ILE 87 45.954 26.,977 29.445 1.00 0.00 0

ATOM 1299 CB ILE 87 48. 069 24. ,641 29. ,709 1. 00 0. 00 c

ATOM 1300 CGI ILE 87 46. 850 24. ,010 28. ,958 1. 00 0. 00 c

ATOM 1301 CG2 ILE 87 48. 046 24. .065 31. ,157 1. 00 0. 00 c

ATOM 1302 CD1 ILE 87 46. ,863 24, .161 27. ,429 1. 00 0. ,00 c

ATOM 1303 H ILE 87 50. ,028 26. .145 30, .939 1. ,00 0. ,00 H

ATOM 1304 HA ILE 87 48. ,120 26, .486 28. .571 1. 00 0. ,00 H

ATOM 1305 HB ILE 87 48. ,968 24, ,212 29. .219 1. ,00 0. ,00 H

ATOM 1306 1HG1 ILE 87 46. ,812 22, ,922 29. .167 1. ,00 0. ,00 H

ATOM 1307 2HG1 ILE 87 45. ,895 24. ,396 29. ,360 1. ,00 0. ,00 H

ATOM 1308 2HG2 ILE 87 48. ,924 24, ,392 31. ,747 1. ,00 0. .00 H

ATOM 1309 3HG2 ILE 87 47, .143 24. ,360 31. .722 1. ,00 0, .00 H

ATOM 1310 1HG2 ILE 87 48. .084 22, .959 31, .162 1. .00 0, .00 H

ATOM 1311 2HD1 ILE 87 46. .797 25. ,217 27, .117 1. .00 0, .00 H

ATOM 1312 3HD1 ILE 87 47. ,781 23. ,741 26, .976 1. .00 0, .00 H

ATOM 1313 1HD1 ILE 87 46, .004 23, .644 26, ,964 1. .00 0. .00 H

ATOM 1314 N LYS 88 46. .689 27. .297 31, .531 0. ,00 0, ,00 N

ATOM 1315 CA LYS 88 45. .283 27, .547 31, ,997 0. ,00 0, .00 C

ATOM 1316 C LYS 88 44. .771 29, .026 31, .836 0. ,00 0, .00 C

ATOM 1317 O LYS 88 45. ,300 29, .963 32, .440 0. ,00 0, .00 O

ATOM 1318 CB LYS 88 45. .118 27, .036 33. .462 0. ,00 0. .00 c

ATOM 1319 CG LYS 88 43, .647 27, .006 33, .972 0. ,00 0, .00 c

ATOM 1320 CD LYS 88 43, .493 26 .612 35, .455 0. ,00 0, .00 c

ATOM 1321 CE LYS 88 42. .028 26, .694 35, .922 0. .00 0. .00 c

ATOM 1322 NZ LYS 88 41, .918 26, .274 37, .333 0. .00 0, .00 N

ATOM 1323 H LYS 88 47, .503 27 .186 32 .144 0. .00 0, .00 H

ATOM 1324 HA LYS 88 44, .598 26, .890 31, .417 0. .00 0, .00 H

ATOM 1325 1HB LYS 88 45, .742 27, .665 34, .128 0. ,00 0, ,00 H

ATOM 1326 2HB LYS 88 45, .548 26 .017 33. .544 0, ,00 0, .00 H

ATOM 1327 1HG LYS 88 43 , .056 26, .319 33, .330 0. .00 0, .00 H

ATOM 1328 2HG LYS 88 43, .188 28 .005 33 .816 0. ,00 0, .00 H

ATOM 1329 1HD LYS 88 44 .138 27 .272 36 .072 0, .00 0, .00 H

ATOM 1330 2HD LYS 88 43 .900 25 .588 35 .595 0. .00 0 .00 H

ATOM 1331 1HE LYS 88 41, .384 26 .057 35 .267 0, .00 0, .00 H

ATOM 1332 2HE LYS 88 41 .631 27 .727 35 .772 0, .00 0, .00 H

ATOM 1333 1HZ LYS 88 40 .954 26 .265 37 .700 1, .00 0 .00 H

ATOM 1334 2HZ LYS 88 42 .246 25 .308 37 .479 1, .00 0, .00 H

ATOM 1335 3HZ LYS 88 42 .474 26 .842 37 .986 1, .00 0, .00 H

ATOM 1336 N VAL 89 43 .662 29 .190 31 .093 1 .00 0 .00 N

ATOM 1337 CA VAL 89 42 .952 30 .499 30 .922 1 .00 0 .00 C

ATOM 1338 C VAL 89 41 .390 30 .302 31 .025 1, .00 0 .00 C

ATOM 1339 0 VAL 89 40 .827 29 .310 30 .547 1 .00 0 .00 O

ATOM 1340 CB VAL 89 43 .467 31 .218 29 .628 1 .00 0 .00 C

ATOM 1341 CGI VAL 89 43 .223 30 .477 28 .301 1, .00 0, .00 C

ATOM 1342 CG2 VAL 89 42 .921 32 .649 29 .457 1, .00 0 .00 C

ATOM 1343 H VAL 89 43 .378 28 .363 30 .558 1 .00 0 .00 H

ATOM 1344 HA VAL 89 43 .233 31 .158 31 .769 1, .00 0, .00 H

ATOM 1345 HB VAL 89 44 .567 31 .313 29 .742 1, .00 0, .00 H

ATOM 1346 1HG1 VAL 89 42 .148 30 .395 28 .060 1 .00 0 .00 H

ATOM 1347 2HG1 VAL 89 43 .717 30 .999 27 .463 1 .00 0 .00 H

ATOM 1348 3HG1 VAL 89 43 .632 29 .449 28 .317 1, .00 0, .00 H

ATOM 1349 2HG2 VAL 89 43 .134 33 .278 30 .342 1, .00 0, .00 H

ATOM 1350 3HG2 VAL 89 43 .365 33 .167 28 .586 1 .00 0 .00 H

ATOM 1351 1HG2 VAL 89 41 .823 32 .659 29 .311 1, .00 0, .00 H

ATOM 1352 N THR 90 40 .681 31 .244 31 .677 1, .00 0, .00 N

ATOM 1353 CA THR 90 39 .213 31 .127 31 .958 1 .00 0, .00 C

ATOM 1354 C THR 90 38 .410 32 .311 31 .312 1 .00 0 .00 C

ATOM 1355 O THR 90 38 .702 33 .486 31 .565 1, .00 0, .00 O

ATOM 1356 CB THR 90 38 .997 31 .014 33 .504 1, .00 0, .00 C

ATOM 1357 OG1 THR 90 39 .783 29 .965 34 .070 1 .00 0, .00 O

ATOM 1358 CG2 THR 90 37 .549 30 .704 33 .915 1, .00 0, .00 C

ATOM 1359 H THR 90 41 .219 32 .048 32 .018 1, .00 0, .00 H

ATOM 1360 HA THR 90 38 .815 30 .187 31 .522 1, .00 0, .00 H

ATOM 1361 HB THR 90 39 .294 31 .973 33 .981 1, .00 0, .00 H

ATOM 1362 HG1 THR 90 39 .696 29 .245 33 .439 1, .00 0, .00 H ATOM 1363 1HG2 THR 90 37.450 30,,584 35.,010 1.,00 0,.00 H

ATOM 1364 2HG2 THR 90 36. 855 31. ,518 33. .629 1. 00 0. .00 H

ATOM 1365 3HG2 THR 90 37. ,162 29. .777 33. ,450 1. ,00 0, .00 H

ATOM 1366 N LEU 91 37. ,378 32. ,002 30, .499 0. ,00 0. .00 N

ATOM 1367 CA LEU 91 36. ,489 33, .029 29, .872 0. ,00 0, .00 C

ATOM 1368 C LEU 91 35. ,202 33, .260 30, .738 0. .00 0, .00 C

ATOM 1369 O LEU 91 34. ,416 32, .335 30, .977 0. ,00 0, .00 O

ATOM 1370 CB LEU 91 36. .101 32, .654 28, .411 0. .00 0, .00 C

ATOM 1371 CG LEU 91 37. ,192 32. ,207 27, .406 0. .00 0. .00 C

ATOM 1372 GDI LEU 91 36. .574 31, .934 26, .026 0. ,00 0. .00 C

ATOM 1373 CD2 LEU 91 38. .332 33, .220 27, .246 0. ,00 0, ,00 c

ATOM 1374 H LEU 91 37, .161 31, .001 30, .421 0. ,00 0, .00 H

ATOM 1375 HA LEU 91 37. .036 33, .993 29 .798 0. .00 0, .00 H

ATOM 1376 1HB LEU 91 35, .553 33, .517 27, .981 0, ,00 0, .00 H

ATOM 1377 2HB LEU 91 35. .338 31, .858 28 .458 0, .00 0, .00 H

ATOM 1378 HG LEU 91 37. .617 31, ,260 27, .791 0, .00 0, .00 H

ATOM 1379 1HD1 LEU 91 37. .331 31, .617 25 .286 0, .00 0, .00 H

ATOM 1380 2HD1 LEU 91 35, .808 31 .142 26 .073 0, .00 0 .00 H

ATOM 1381 3HD1 LEU 91 36. .079 32, .835 25 .613 0, .00 0, .00 H

ATOM 1382 1HD2 LEU 91 39. .094 32 .888 26 .518 0, .00 0, .00 H

ATOM 1383 2HD2 LEU 91 37. ,952 34, .201 26, .909 0, .00 0, .00 H

ATOM 1384 3HD2 LEU 91 38, .856 33 .387 28 .204 0, .00 0, .00 H

ATOM 1385 N VAL 92 34, .992 34, .497 31, .202 0, .00 0, .00 N

ATOM 1386 CA VAL 92 33, .904 34 .842 3 .163 0, .00 0, .00 C

ATOM 1387 C VAL 92 32, .744 35 .541 31 .368 0, .00 0 .00 C

ATOM 1388 O VAL 92 32, .825 36 .737 31 .073 0, .00 0, .00 O

ATOM 1389 CB VAL 92 34, .498 35 .727 33 .324 0, .00 0 .00 C

ATOM 1390 CGI VAL 92 33, .460 36, .071 34 .411 0, .00 0, .00 C

ATOM 1391 CG2 VAL 92 35, .726 35 .135 34 .064 0, .00 0, .00 C

ATOM 1392 H VAL 92 35, .726 35, .192 31 .013 0, ,00 0, .00 H

ATOM 1393 HA VAL 92 33, .494 33 .930 32 .643 0, .00 0, .00 H

ATOM 1394 HB VAL 92 34 .805 36 .697 32 .887 0, .00 0 .00 H

ATOM 1395 1HG1 VAL 92 33, .864 36 .753 35 .184 0, .00 0, .00 H

ATOM 1396 2HG1 VAL 92 32 .579 36 .592 33 .991 0, .00 0 .00 H

ATOM 1397 3HG1 VAL 92 33, .086 35 .174 3 .933 0, .00 0. .00 H

ATOM 1398 1HG2 VAL 92 36 .103 35 .830 34 .839 0, .00 0 .00 H

ATOM 1399 2HG2 VAL 92 35 .486 34 .181 34 .568 0 .00 0 .00 H

ATOM 1400 3HG2 VAL 92 36 .572 34 .946 33 .379 0, .00 0 .00 H

ATOM 1401 N PHE 93 31 .681 34 .804 31 .003 0 .00 0 .00 N

ATOM 1402 CA PHE 93 30 .540 35 .356 30 .209 0, .00 0 .00 C

ATOM 1403 C PHE 93 29 .288 35 .691 31 .092 0 .00 0 .00 C

ATOM 1404 0 PHE 93 29 .065 35 .118 32 .161 0, .00 0 .00 O

ATOM 1405 CB PHE 93 30 .155 34 .351 29 .081 0 .00 0 .00 C

ATOM 1406 CG PHE 93 31 .174 34 .106 27 .956 0 .00 0 .00 C

ATOM 1407 CD1 PHE 93 31 .971 32 .959 27 .975 0, .00 0 .00 C

ATOM 1408 CE1 PHE 93 32 .823 32 .675 26 .910 0 .00 0 .00 C

ATOM 1409 CZ PHE 93 32 .884 33 .541 25 .819 0, .00 0, .00 C

ATOM 1410 CE2 PHE 93 32 .094 34 .685 25 .792 0 .00 0 .00 C

ATOM 1411 CD2 PHE 93 31. .245 34 .975 26, .860 0, .00 0, .00 C

ATOM 1412 H PHE 93 31 .705 33 .816 31 .281 0, .00 0, .00 H

ATOM 1413 HA PHE 93 30 .841 36 .302 29 .714 0, .00 0 .00 H

ATOM 1414 1HB PHE 93 29. .214 34 .692 28, .605 0, .00 0, .00 H

ATOM 1415 2HB PHE 93 29 .861 33 .389 29 .537 0, .00 0 .00 H

ATOM 1416 HD1 PHE 93 31, .918 32 .279 28, .814 0, .00 0, .00 H

ATOM 1417 HE1 PHE 93 33 .424 31 .780 26, .927 0, .00 0, .00 H

ATOM 1418 HZ PHE 93 33 .534 33 .323 24 .985 0, .00 0 .00 H

ATOM 1419 HE2 PHE 93 32. .130 35 .353 24, .943 0, ,00 0, .00 H

ATOM 1420 HD2 PHE 93 30 .631 35 .865 26, .829 0, .00 0, .00 H

ATOM 1421 N GLU 94 28, .409 36 .574 30, .601 0, .00 0, .00 N

ATOM 1422 CA GLU 94 27 .073 36 .831 31, .210 0. .00 0, .00 C

ATOM 1423 C GLU 94 26, .098 35, .598 31, .090 0. .00 0. .00 C

ATOM 1424 O GLU 94 25, .894 35, .065 29. .994 0, .00 0, .00 O

ATOM 1425 CB GLU 94 26, .553 38 .113 30. .506 0, .00 0, .00 C

ATOM 1426 CG GLU 94 25, .282 38, .741 31. .133 0. .00 0. .00 C

ATOM 1427 CD GLU 94 24, .840 40 .060 30, .497 0. .00 0. .00 C ATOM 1428 OE1 GLU 94 25.,603 40.,952 30.,138 0.00 0..00 0

ATOM 1429 OE2 GLU 94 23. ,487 40. .153 30. ,402 0. ,00 0. ,00 0

ATOM 1430 H GLU 94 28. ,733 37. ,098 29. ,779 0. 00 0. ,00 H

ATOM 1431 HA GLU 94 27, ,224 37. ,077 32. ,281 0. ,00 0. ,00 H

ATOM 1432 1HB GLU 94 26. ,368 37. .903 29, .435 0. ,00 0. .00 H

ATOM 1433 2HB GLU 94 27, ,346 38. .889 30, .515 0. ,00 0. .00 H

ATOM 1434 1HG GLU 94 25. ,433 38. ,959 32. .203 0. ,00 0. ,00 H

ATOM 1435 2HG GLU 94 24, ,429 38. .039 31. .091 0. ,00 0. ,00 H

ATOM 1436 N HIS 95 25, ,522 35, .121 32, .213 1, .00 0. .00 N

ATOM 1437 CA HIS 95 24. ,674 33. ,892 32, .217 1, .00 0. ,00 C

ATOM 1438 C HIS 95 23. ,237 34. .101 31, .616 1. .00 0. .00 C

ATOM 1439 O HIS 95 22. .535 35. .065 31, .934 1. .00 0. .00 O

ATOM 1440 CB HIS 95 24, .629 33, .323 33, .665 1, .00 0. .00 C

ATOM 1441 CG HIS 95 24. .204 31, .855 33, .754 1. .00 0. ,00 C

ATOM 1442 ND1 HIS 95 22. .890 31, .437 33, .900 1. .00 0. .00 N

ATOM 1443 CE1 HIS 95 23, .076 30, .083 33, .788 1, ,00 0. .00 C

ATOM 1444 NE2 HIS 95 24, .329 29, .576 33, .591 1. .00 0. .00 N

ATOM 1445 CD2 HIS 95 25. .056 30, .749 33, .595 1. .00 0. .00 C

ATOM 1446 H HIS 95 25, .698 35, .679 33, .056 1, ,00 0. .00 H

ATOM 1447 HA HIS 95 25, .203 33, .143 31, .592 1, .00 0. .00 H

ATOM 1448 1HB HIS 95 25, .621 33, .411 34, .139 1, .00 0, .00 H

ATOM 1449 2HB HIS 95 23, .967 33 .950 34 .293 1, .00 0, .00 H

ATOM 1450 HE1 HIS 95 22, .209 29, .435 33, .739 1, ,00 0, .00 H

ATOM 1451 HE2 HIS 95 24, .609 28 .624 33 .330 1, .00 0, .00 H

ATOM 1452 HD2 HIS 95 26, .120 30 .818 33 .434 1. ,00 0, .00 H

ATOM 1453 N VAL 96 22, .807 33 .154 30 .769 1, .00 0, .00 N

ATOM 1454 CA VAL 96 21, .410 33, .087 30 .240 1, ,00 0, .00 C

ATOM 1455 C VAL 96 20, .817 31 .683 30 .617 1, .00 0, .00 C

ATOM 1456 O VAL 96 21, .453 30 .641 30 .426 1, ,00 0, .00 O

ATOM 1457 CB VAL 96 21, .394 33 .381 28 .701 1, .00 0, .00 C

ATOM 1458 CGI VAL 96 19, .997 33, .226 28 .053 1. .00 0. .00 C

ATOM 1459 CG2 VAL 96 21, .886 34 .797 28 .321 1, .00 0, .00 C

ATOM 1460 H VAL 96 23, .456 32, .378 30 .619 1, .00 0, .00 H

ATOM 1461 HA VAL 96 20, .779 33 .862 30 .723 1, .00 0, .00 H

ATOM 1462 HB VAL 96 22, .072 32 .647 28 .224 1, .00 0, .00 H

ATOM 1463 1HG1 VAL 96 19 .225 33 .822 28 .570 1, .00 0, .00 H

ATOM 1464 2HG1 VAL 96 19 .977 33 .528 26 .990 1, .00 0 .00 H

ATOM 1465 3HG1 VAL 96 19 .646 32 .175 28 .072 1, .00 0, .00 H

ATOM 1466 2HG2 VAL 96 22 .912 34 .986 28 .688 1, .00 0 .00 H

ATOM 1467 3HG2 VAL 96 21, .910 34 .942 27 .227 1, .00 0, .00 H

ATOM 1468 1HG2 VAL 96 21 .241 35 .587 28 .752 1, .00 0, .00 H

ATOM 1469 N ASP 97 19, .576 31 .653 31 .133 1, .00 0, .00 N

ATOM 1470 CA ASP 97 18 .943 30 .402 31 .656 1, .00 0 .00 C

ATOM 1471 C ASP 97 18, .600 29 .223 30 .667 1, .00 0, .00 C

ATOM 1472 O ASP 97 18 .510 28 .079 31 .120 1, .00 0, .00 O

ATOM 1473 CB ASP 97 17. .740 30 .821 32 .550 1, .00 0, .00 C

ATOM 1474 CG ASP 97 16, .481 31 .307 31 .827 1, .00 0, .00 C

ATOM 1475 OD1 ASP 97 16, .279 32 .476 31 .513 1, .00 0, .00 O

ATOM 1476 OD2 ASP 97 15 ,613 30 .291 31 .568 1, .00 0, .00 O

ATOM 1477 H ASP 97 19 .078 32 .548 31 .185 1, .00 0, .00 H

ATOM 1478 HA ASP 97 19, .677 29 .954 32 .353 1, .00 0, .00 H

ATOM 1479 1HB ASP 97 17 .446 29 .962 33 .177 1, .00 0, .00 H

ATOM 1480 2HB ASP 97 18, .039 31 .603 33 .270 1, .00 0. .00 H

ATOM 1481 N GLN 98 18 .362 29 .478 29 .366 0, .00 0, .00 N

ATOM 1482 CA GLN 98 18. .028 28 .418 28 .369 0. .00 0. .00 C

ATOM 1483 C GLN 98 18, .736 28 .654 26 .985 0. .00 0, ,00 C

ATOM 1484 O GLN 98 19, .153 29 .762 26, .638 0, .00 0. .00 O

ATOM 1485 CB GLN 98 16, .471 28 .327 28 .297 0, .00 0. ,00 C

ATOM 1486 CG GLN 98 15, ,912 27, .071 27, .570 0, .00 0. ,00 C

ATOM 1487 CD GLN 98 14, .413 26 .811 27 .719 0, .00 0. .00 C

ATOM 1488 OE1 GLN 98 13. ,621 27. ,004 26. .809 0. .00 0. ,00 O

ATOM 1489 NE2 GLN 98 13, ,975 26, .324 28, .852 0, ,00 0, .00 N

ATOM 1490 H GLN 98 18, .390 30 .473 29 .120 0, ,00 0, .00 H

ATOM 1491 HA GLN 98 18. .414 27, .446 28, .740 0. .00 0. ,00 H

ATOM 1492 1HB GLN 98 16. .070 29 .248 27, .827 0. .00 0. ,00 H ATOM 1493 2HB GLN 98 16.067 28.353 29.330 0.00 0.00 H

ATOM 1494 1HG GLN 98 16. 468 26. ,168 27. 882 0. 00 0. ,00 H

ATOM 1495 2HG GLN 98 16. 121 27. 157 26. 486 0. 00 0. .00 H

ATOM 1496 1HE2 GLN 98 14. 648 26. ,528 29. 599 0. 00 0. ,00 H

ATOM 1497 2HE2 GLN 98 12. 964 26. 468 28. 893 0. 00 0. ,00 H

ATOM 1498 N ASP 99 18. ,871 27. ,588 26. 182 0. 00 0. ,00 N

ATOM 1499 CA ASP 99 19. ,311 27. ,670 24. ,757 0. ,00 0, .00 C

ATOM 1500 C ASP 99 18. ,143 27. ,443 23. 729 0. 00 0. ,00 C

ATOM 1501 O ASP 99 17. ,108 26. .852 24. ,053 0. ,00 0. ,00 O

ATOM 1502 CB ASP 99 20. ,522 26. ,710 24. 573 0. ,00 0. ,00 C

ATOM 1503 CG ASP 99 20. ,202 25. .217 24. ,599 0. ,00 0, .00 C

ATOM 1504 OD1 ASP 99 19, .876 24. .584 23. ,603 0. ,00 0, .00 O

ATOM 1505 OD2 ASP 99 20. .248 24, .691 25. 851 0. ,00 0, .00 O

ATOM 1506 H ASP 99 18, .652 26. ,669 26. ,580 0. ,00 0, ,00 H

ATOM 1507 HA ASP 99 19. ,704 28, ,679 24. ,548 0. ,00 0, ,00 H

ATOM 1508 1HB ASP 99 21, .310 26, ,916 25. ,319 0. ,00 0. .00 H

ATOM 1509 2HB ASP 99 21. .007 26, .915 23, .602 0, .00 0, .00 H

ATOM 1510 N LEU 100 18. .349 27. ,842 22. ,463 0. .00 0. .00 N

ATOM 1511 CA LEU 100 17. .388 27, .574 21. .352 0. .00 0, .00 C

ATOM 1512 C LEU 100 17. .109 26, ,062 21. .034 0. .00 0, ,00 C

ATOM 1513 O LEU 100 15. .945 25, .714 20, .857 0. .00 0, .00 O

ATOM 1514 CB LEU 100 17. .832 28, .405 20, .116 0, .00 0, ,00 C

ATOM 1515 CG LEU 100 16. .861 28, .460 18, .905 0, ,00 0, .00 C

ATOM 1516 CD1 LEU 100 15, .564 29, .223 19. .217 0, .00 0, .00 C

ATOM 1517 CD2 LEU 100 17, ,560 29, .126 17, .711 0, .00 0, ,00 C

ATOM 1518 H LEU 100 19, .273 28, .273 22, ,312 0, .00 0, .00 H

ATOM 1519 HA LEU 100 16. .420 27, .994 21, .679 0, .00 0, .00 H

ATOM 1520 1HB LEU 100 18, .805 28, .011 19. .777 0. .00 0, .00 H

ATOM 1521 2HB LEU 100 18 .059 29 .442 20. .434 0, .00 0 .00 H

ATOM 1522 HG LEU 100 16, .596 27, .424 18, .607 0, .00 0, .00 H

ATOM 1523 1HD1 LEU 100 14, .891 29 .267 18, .341 0, .00 0, .00 H

ATOM 1524 2HD1 LEU 100 14 .993 28 .732 20, .025 0 .00 0 .00 H

ATOM 1525 3HD1 LEU 100 15, .759 30 .264 19, .539 0, .00 0, .00 H

ATOM 1526 1HD2 LEU 100 16 .898 29 .188 16, .828 0 .00 0 .00 H

ATOM 1527 2HD2 LEU 100 17 .892 30 .155 17. .943 0, .00 0, .00 H

ATOM 1528 3HD2 LEU 100 18 .456 28 .562 17, .394 0 .00 0. .00 H

ATOM 1529 N ARG 101 18 .109 25 .157 21, .010 1 .00 0 .00 N

ATOM 1530 CA ARG 101 17 .866 23 .676 20, .954 1 .00 0, .00 C

ATOM 1531 C ARG 101 16 .888 23 .087 22, .041 1 .00 0 .00 C

ATOM 1532 0 ARG 101 15 .963 22 .340 21, .717 1, .00 0, .00 O

ATOM 1533 CB ARG 101 19 .269 22 .995 20, .961 1 .00 0 .00 C

ATOM 1534 CG ARG 101 19 .315 21 .472 20 .683 1 .00 0 .00 C

ATOM 1535 CD ARG 101 18 .930 21 .093 19, .245 1 .00 0 .00 c

ATOM 1536 NE ARG 101 19 .031 19 .619 19 .099 1 .00 0 .00 N

ATOM 1537 CZ ARG 101 18 .804 18 .939 17, .982 1 .00 0 .00 C

ATOM 1538 NH1 ARG 101 18 .478 19 .483 16 .848 1 .00 0 .00 N

ATOM 1539 NH2 ARG 101 18 .915 17 .659 18 .033 1 .00 0 .00 N

ATOM 1540 H ARG 101 18 .975 25 .523 21 .437 1 .00 0 .00 H

ATOM 1541 HA ARG 101 17 .384 23 .470 19 .981 1 .00 0 .00 H

ATOM 1542 1HB ARG 101 19 .956 23 .510 20, .267 1 .00 0 .00 H

ATOM 1543 2HB ARG 101 19 .757 23 .128 21 .938 1 .00 0 .00 H

ATOM 1544 1HG ARG 101 20 .340 21 .125 20 .930 1 .00 0 .00 H

ATOM 1545 2HG ARG 101 18 .659 20 .960 21 .420 1 .00 0 .00 H

ATOM 1546 1HD ARG 101 17 .891 21 .435 19 .044 1 .00 0 .00 H

ATOM 1547 2HD ARG 101 19 .588 21 .631 18, .530 1 .00 0 .00 H

ATOM 1548 HE ARG 101 19 .185 19 .063 19 .948 1 .00 0 .00 H

ATOM 1549 2HH1 ARG 101 18 .321 20 .497 16 .922 1 .00 0 .00 H

ATOM 1550 1HH1 ARG 101 18 .242 18 .896 16, .055 1 .00 0 .00 H

ATOM 1551 1HH2 ARG 101 19 .089 17 .298 18 .974 1 .00 0 .00 H

ATOM 1552 2HH2 ARG 101 18 .667 17 .134 17, .199 1, .00 0, .00 H

ATOM 1553 N THR 102 17 .079 23 .472 23 .312 1 .00 0 .00 N

ATOM 1554 CA THR 102 16 .113 23 .218 24 .424 1 .00 0 .00 C

ATOM 1555 C THR 102 14 .701 23 .901 24, .255 1 .00 0, .00 C

ATOM 1556 0 THR 102 13 .686 23 .215 24, .379 1 .00 0 .00 O

ATOM 1557 CB THR 102 16 .863 23 .594 25, .746 1, .00 0, .00 C ATOM 1558 OG1 THR 102 18.106 22.897 25.856 00 ,00 0

ATOM 1559 CG2 THR 102 16.107 23.271 27.040 00 ,00 c

ATOM 1560 H THR 102 17.955 24.012 23.454 00 ,00 H

ATOM 1561 HA THR 102 15.921 22.127 24.450 00 .00 H

ATOM 1562 HB THR 102 17.099 24.680 25.725 00 .00 H

ATOM 1563 HG1 THR 102 18.278 22.444 25.024 00 0.00 H

ATOM 1564 1HG2 THR 102 16.729 23.538 27.914 00 0.00 H

ATOM 1565 2HG2 THR 102 15.164 23.842 27.099 00 0.00 H

ATOM 1566 3HG2 THR 102 15.880 22.192 27.103 00 0.00 H

ATOM 1567 N TYR 103 14.629 25.208 23.936 00 0.00 N

ATOM 1568 CA TYR 103 13.356 25.917 23.586 00 0.00 c

ATOM 1569 C TYR 103 12.533 25.340 22.371 00 0.00 c

ATOM 1570 O TYR 103 11.315 25.189 22.484 00 0.00 0

ATOM 1571 CB TYR 103 13.748 27.415 23.422 00 ,00 c

ATOM 1572 CG TYR 103 12.599 28.419 23.217 00 ,00 c

ATOM 1573 CD1 TYR 103 11.813 28.828 24.300 00 .00 c

ATOM 1574 CD2 TYR 103 12.337 28.941 21.945 00 .00 c

ATOM 1575 CE1 TYR 103 10.775 29.738 24.109 00 ,00 c

ATOM 1576 CE2 TYR 103 11.303 29.856 21.759 00 ,00 c

ATOM 1577 CZ TYR 103 10.522 30.252 22.841 00 ,00 c

ATOM 1578 OH TYR 103 9.495 31.137 22.657 00 .00 o

ATOM 1579 H TYR 103 15.554 25.665 23.872 00 .00 H

ATOM 1580 HA TYR 103 12.687 25.849 24.466 00 .00 H

ATOM 1581 1HB TYR 103 14.333 27.749 24.304 00 .00 H

ATOM 1582 2HB TYR 103 14.470 27.503 22.589 00 .00 H

ATOM 1583 HD1 TYR 103 12.012 28.445 25.291 00 0.00 H

ATOM 1584 HD2 TYR 103 12.927 28.627 21.097 00 0.00 H

ATOM 1585 HE1 TYR 103 10.171 30.055 24.947 00 0.00 H

ATOM 1586 HE2 TYR 103 11.110 30.250 20.772 00 0.00 H

ATOM 1587 HH TYR 103 9.483 31.401 21.736 00 0.00 H

ATOM 1588 N LEU 104 13.174 24.986 21.240 00 0.00 N

ATOM 1589 CA LEU 104 12.531 24.217 20.127 00 00 c

ATOM 1590 C LEU 104 11.891 22.835 20.519 00 00 c

ATOM 1591 O LEU 104 10.752 22.561 20.132 00 00 o

ATOM 1592 CB LEU 104 13.575 24.029 18.983 00 00 c

ATOM 1593 CG LEU 104 14.096 25.283 18.228 1.00 00 c

ATOM 1594 GDI LEU 104 15.237 24.881 17.286 ,00 00 c

ATOM 1595 CD2 LEU 104 12.997 25.987 17.425 ,00 00 c

ATOM 1596 H LEU 104 14.195 25.136 21.276 ,00 0.00 H

ATOM 1597 HA LEU 104 11.697 24.828 19.734 ,00 0.00 H

ATOM 1598 1HB LEU 104 14.443 23.485 19.409 ,00 00 H

ATOM 1599 2HB LEU 104 13.165 23.327 18.232 .00 00 H

ATOM 1600 HG LEU 104 14.496 26.013 18.957 ,00 00 H

ATOM 1601 2HD1 LEU 104 16.094 24.461 17.845 1.00 00 H

ATOM 1602 3HD1 LEU 104 14.924 24.109 16.561 1.00 00 H

ATOM 1603 1HD1 LEU 104 15.630 25.738 16.708 1.00 00 H

ATOM 1604 2HD2 LEU 104 12.511 25.312 16.697 1.00 00 H

ATOM 1605 3HD2 LEU 104 12.214 26.385 18.091 1.00 00 H

ATOM 1606 1HD2 LEU 104 13.395 26.846 16.854 1.00 00 H

ATOM 1607 N ASP 105 12.586 21.995 21.309 0.00 00 N

ATOM 1608 CA ASP 105 11.977 20.779 21.938 00 0.00 C

ATOM 1609 C ASP 105 10.781 21.016 22.941 00 0.00 C

ATOM 1610 O ASP 105 9.928 20.138 23.079 00 00 O

ATOM 1611 CB ASP 105 13.113 19.963 22.618 00 00 C

ATOM 1612 CG ASP 105 14.183 19.377 21.693 00 00 C

ATOM 1613 OD1 ASP 105 13.948 18.854 20.609 00 00 O

ATOM 1614 OD2 ASP 105 15.434 19.488 22.215 00 00 O

ATOM 1615 H ASP 105 13.550 22.282 21.528 00 00 H

ATOM 1616 HA ASP 105 11.567 20.149 21.125 00 0.00 H

ATOM 1617 1HB ASP 105 12.683 19.104 23.161 00 0.00 H

ATOM 1618 2HB ASP 105 13.608 20.579 23.392 0.00 00 H

ATOM 1619 N LYS 106 10.719 22.165 23.637 0.00 00 N

ATOM 1620 CA LYS 106 9.631 22.496 24.611 0.00 00 C

ATOM 1621 C LYS 106 8.404 23.339 24.081 0.00 00 C

ATOM 1622 O LYS 106 7.535 23.685 24.888 0.00 00 O ATOM 1623 CB LYS 106 10.333 23.204 25.811 0.00 0.00 C

ATOM 1624 CG LYS 106 11.225 22.297 26.696 0.00 0.00 c

ATOM 1625 CD LYS 106 11.949 23.082 27.805 ,00 0.00 c

ATOM 1626 CE LYS 106 12.792 22.156 28.693 ,00 00 c

ATOM 1627 NZ LYS 106 13.507 22.955 29.707 ,00 00 N

ATOM 1628 H LYS 106 11.518 22.784 23.442 ,00 0.00 H

ATOM 1629 HA LYS 106 9.174 21.562 24.994 .00 0.00 H

ATOM 1630 1HB LYS 106 9.565 23.668 26.460 ,00 00 H

ATOM 1631 2HB LYS 106 10.921 24.066 25.429 .00 00 H

ATOM 1632 1HG LYS 106 11.975 21.795 26.047 .00 00 H

ATOM 1633 2HG LYS 106 10.607 21.480 27.117 .00 0.00 H

ATOM 1634 1HD LYS 106 11.204 23.645 28.404 .00 0.00 H

ATOM 1635 2HD LYS 106 12.586 23.856 27.321 ,00 00 H

ATOM 1636 1HE LYS 106 13.510 21.591 28.050 ,00 00 H

ATOM 1637 2HE LYS 106 12.148 21.375 29.158 ,00 0.00 H

ATOM 1638 1HZ LYS 106 14.130 22.415 30.321 ,00 0.00 H

ATOM 1639 2HZ LYS 106 14.117 23.659 29.259 .00 00 H

ATOM 1640 3HZ LYS 106 12.884 23.510 30.308 .00 00 H

ATOM 1641 N ALA 107 8.286 23.675 22.781 .00 00 N

ATOM 1642 CA ALA 107 7.174 24.513 22.252 .00 00 c

ATOM 1643 c ALA 107 5.817 23.733 21.998 .00 00 c

ATOM 1644 O ALA 107 5.856 22.702 21.315 .00 00 0

ATOM 1645 CB ALA 107 7.727 25.162 20.972 .00 00 c

ATOM 1646 H ALA 107 9.098 23.397 22.216 .00 00 H

ATOM 1647 HA ALA 107 7.004 25.342 22.964 .00 00 H

ATOM 1648 2HB ALA 107 8.638 25.761 21.175 .00 00 H

ATOM 1649 3HB ALA 107 8.003 24.405 20.220 .00 00 H

ATOM 1650 1HB ALA 107 6.994 25.848 20.511 .00 00 H

ATOM 1651 N PRO 108 4.616 24.155 22.504 .00 00 N

ATOM 1652 CA PRO 108 3, .357 23.360 22.367 .00 00 c

ATOM 1653 CD PRO 108 4, .460 25.362 23.343 .00 00 c

ATOM 1654 C PRO 108 2. .589 23.481 20.992 .00 00 c

ATOM 1655 O PRO 108 2, .696 24.528 20.348 .00 00 o

ATOM 1656 CB PRO 108 2, .544 23.910 23.556 0.00 00 c

ATOM 1657 CG PRO 108 2, .970 25.375 23.684 0.00 00 c

ATOM 1658 HA PRO 108 3 .586 22.293 22.552 .00 00 H

ATOM 1659 1HD PRO 108 4, .762 26.285 22.808 .00 00 H

ATOM 1660 2HD PRO 108 5. .073 25.284 24.264 .00 00 H

ATOM 1661 1HB PRO 108 2, .809 23.360 24.481 .00 00 H

ATOM 1662 2HB PRO 108 1. .450 23.802 23.430 .00 0.00 H

ATOM 1663 1HG PRO 108 2, .766 25.802 24.684 .00 0.00 H

ATOM 1664 2HG PRO 108 2. .423 25.996 22.947 .00 0.00 H

ATOM 1665 N PRO 109 1. .783 22.482 20.511 .00 0.00 N

ATOM 1666 CA PRO 109 1. .155 22.529 19.153 1.00 0.00 c

ATOM 1667 C PRO 109 0. .060 23.648 18.921 00 0.00 c

ATOM 1668 O PRO 109 -0.783 23.826 19.808 00 0.00 o

ATOM 1669 CB PRO 109 0.606 21.092 19.024 00 0.00 c

ATOM 1670 CG PRO 109 0.332 20.637 20.460 00 0.00 c

ATOM 1671 CD PRO 109 1.483 21.244 21.258 00 0.00 c

ATOM 1672 HA PRO 109 1.962 22.655 18.415 00 .00 H

ATOM 1673 1HB PRO 109 -0.297 21.029 18.386 00 .00 H

ATOM 1674 2HB PRO 109 1.363 20.435 18.557 00 .00 H

ATOM 1675 1HG PRO 109 -0.634 21.054 20.812 00 .00 H

ATOM 1676 2HG PRO 109 0.269 19.538 20.565 00 .00 H

ATOM 1677 1HD PRO 109 1.182 21.439 22.307 00 .00 H

ATOM 1678 2HD PRO 109 2.364 20.573 21.276 00 .00 H

ATOM 1679 N PRO 110 0, .004 24.423 17.788 00 .00 N

ATOM 1680 CA PRO 110 0. .804 24.184 16.543 00 .00 C

ATOM 1681 CD PRO 110 -1, .015 25.483 17.631 00 .00 C

ATOM 1682 C PRO 110 2 ..346 24.493 16.503 00 .00 C

ATOM 1683 O PRO 110 3 .,009 24.046 15.565 00 .00 O

ATOM 1684 CB PRO 110 0 .,000 24.999 15.502 00 .00 C

ATOM 1685 CG PRO 110 -0.679 26.124 16.286 00 .00 C

ATOM 1686 HA PRO 110 0.715 23.118 16.260 00 .00 H

ATOM 1687 1HD PRO 110 -0.981 26.221 18.458 00 0.00 H ATOM 1688 2HD PRO 110 -2.,033 25..046 17.,624 0.,00 0.,00 H

ATOM 1689 1HB PRO 110 -0. 771 24. ,356 15. 034 0. ,00 0. .00 H

ATOM 1690 2HB PRO 110 0. ,617 25. .386 14. ,667 0. ,00 0. ,00 H

ATOM 1691 1HG PRO 110 -1. ,569 26, .534 15, .772 0. .00 0. .00 H

ATOM 1692 2HG PRO 110 0. ,026 26. .966 16. ,432 0. ,00 0. ,00 H

ATOM 1693 N GLY 111 2. .921 25. .183 17, .499 0, .00 0, ,00 N

ATOM 1694 CA GLY 111 4. ,398 25. .222 17. ,713 0. ,00 0. ,00 C

ATOM 1695 C GLY 111 4. ,905 26. .595 18. .183 0. .00 0. .00 C

ATOM 1696 O GLY 111 4. .898 26, ,906 19. .377 0. .00 0. .00 O

ATOM 1697 H GLY 111 2, ,264 25. ,446 18, .248 0, ,00 0, .00 H

ATOM 1698 1HA GLY 111 4, ,962 24, .908 16, ,815 0. .00 0, .00 H

ATOM 1699 2HA GLY 111 4. ,668 24. .492 18, ,499 0. .00 0, ,00 H

ATOM 1700 N LEU 112 5, ,372 27. .409 17, .231 1, ,00 0, .00 N

ATOM 1701 CA LEU 112 5. ,871 28. ,786 17. .503 1. ,00 0, ,00 C

ATOM 1702 C LEU 112 5, .012 29. .823 16. ,689 1. ,00 0, .00 C

ATOM 1703 O LEU 112 4. ,905 29. ,662 15, ,466 1. ,00 0, .00 O

ATOM 1704 CB LEU 112 7, ,386 28, .892 17. ,169 1. ,00 0, .00 C

ATOM 1705 CG LEU 112 8, .378 28, .182 18, .128 1, ,00 0, .00 c

ATOM 1706 GDI LEU 112 9, ,798 28, .267 17. ,551 1, .00 0, .00 c

ATOM 1707 CD2 LEU 112 8, .389 28, .784 19. .545 1. .00 0, .00 c

ATOM 1708 H LEU 112 5, .229 27, .086 16. .269 1. .00 0, .00 H

ATOM 1709 HA LEU 112 5, .764 29, .022 18, .576 1. .00 0, .00 H

ATOM 1710 1HB LEU 112 7, ,548 28, .529 16. ,135 1. ,00 0, .00 H

ATOM 1711 2HB LEU 112 7, .664 29, .964 17, .122 1, .00 0, .00 H

ATOM 1712 HG LEU 112 8, .101 27, .111 18, .203 1, .00 0, .00 H

ATOM 1713 2HD1 LEU 112 9, .879 27, .758 16, .572 1. ,00 0, .00 H

ATOM 1714 3HD1 LEU 112 10, .125 29, .313 17, .399 1, .00 0. .00 H

ATOM 1715 1HD1 LEU 112 10, .538 27, .797 18, .222 1, ,00 0, .00 H

ATOM 1716 2HD2 LEU 112 8, .623 29, .865 19, .539 1, .00 0. .00 H

ATOM 1717 3HD2 LEU 112 7 .417 28 .659 20, .057 1, .00 0 .00 H

ATOM 1718 1HD2 LEU 112 9, .139 28, .292 20, .195 1. .00 0, .00 H

ATOM 1719 N PRO 113 4 .391 30 .894 17 .272 0, .00 0 .00 N

ATOM 1720 CA PRO 113 3, .547 31, .845 16, .496 0. .00 0, .00 C

ATOM 1721 CD PRO 113 4, .463 31 .210 18, .714 0, .00 0, .00 C

ATOM 1722 C PRO 113 4, .369 32, .899 15, .674 0, .00 0, .00 C

ATOM 1723 O PRO 113 5 .423 33, .374 16 .108 0. .00 0, .00 O

ATOM 1724 CB PRO 113 2 .687 32 .438 17 .629 0, .00 0 .00 C

ATOM 1725 CG PRO 113 3, .618 32, .479 18, .844 0, .00 0, .00 C

ATOM 1726 HA PRO 113 2 .886 31 .284 15 .805 0, .00 0 .00 H

ATOM 1727 1HD PRO 113 5, .502 31, .383 19, .059 0, .00 0, .00 H

ATOM 1728 2HD PRO 113 4 .030 30 .390 19 .321 0, .00 0 .00 H

ATOM 1729 1HB PRO 113 1, .819 31, .780 17, .835 0, .00 0 .00 H

ATOM 1730 2HB PRO 113 2, .272 33 .435 17, .382 0, .00 0 .00 H

ATOM 1731 1HG PRO 113 3 .073 32 .536 19 .804 0 .00 0 .00 H

ATOM 1732 2HG PRO 113 4 .262 33, .378 18, .791 0, .00 0, .00 H

ATOM 1733 N ALA 114 3 .873 33 .277 14 .485 1, .00 0 .00 N

ATOM 1734 CA ALA 114 4 .651 34, .098 13, .511 1, .00 0, .00 C

ATOM 1735 C ALA 114 5 .186 35 .516 13 .932 1, .00 0 .00 C

ATOM 1736 0 ALA 114 6 .250 35 .905 13 .451 1 .00 0 .00 O

ATOM 1737 CB ALA 114 3 .804 34, .147 12 .226 1, .00 0, .00 C

ATOM 1738 H ALA 114 3 .015 32 .793 1 .208 1 .00 0 .00 H

ATOM 1739 HA ALA 114 5 .562 33, .520 13 .258 1, .00 0, .00 H

ATOM 1740 2HB ALA 114 3, .540 33 .140 11 .851 1, .00 0 .00 H

ATOM 1741 3HB ALA 114 2, .861 34, .710 12, .366 1. .00 0, .00 H

ATOM 1742 1HB ALA 114 4 .349 34, .646 11 .402 1, .00 0, .00 H

ATOM 1743 N GLU 115 .518 36 .268 14 .828 0 .00 0 .00 N

ATOM 1744 CA GLU 115 5. .121 37, .484 15, .473 0, .00 0, .00 C

ATOM 1745 C GLU 115 6 .306 37, .214 16 .470 0 .00 0 .00 C

ATOM 1746 O GLU 115 7, .282 37, ,967 16, .464 0, .00 0, .00 O

ATOM 1747 CB GLU 115 3 .998 38, .334 16 .129 0, .00 0, .00 C

ATOM 1748 CG GLU 115 3. .071 39, .079 15, .130 0, .00 0, .00 C

ATOM 1749 CD GLU 115 1, .951 39, ,917 15, .749 0. .00 0, .00 C

ATOM 1750 OE1 GLU 115 1 .579 39, .843 16 .916 0. .00 0, .00 O

ATOM 1751 OE2 GLU 115 1, .388 40. .757 14, .840 0. .00 0, .00 O

ATOM 1752 H GLU 115 3, .634 35, ,866 15, .152 0. .00 0, .00 H ATOM 1753 HA GLU 115 5 , . 560 38.113 14.674 00 0.00 H

ATOM 1754 1HB GLU 115 4 ..452 39.101 16.788 00 0.00 H

ATOM 1755 2HB GLU 115 3 , .392 37.712 16.817 00 0.00 H

ATOM 1756 1HG GLU 115 2 ..573 38.374 14.446 00 0.00 H

ATOM 1757 2HG GLU 115 3 , . 653 39.766 14.496 00 00 H

ATOM 1758 N THR 115 6 .. 262 36.140 17.285 00 00 N

ATOM 1759 CA THR 116 7 .465 35.583 17.983 00 00 C

ATOM 1760 C THR 116 8 . 606 35.149 16.996 00 00 c

ATOM 1761 O THR 116 . 754 35.520 17.234 00 00 0

ATOM 1762 CB THR 116 . 025 34.456 18.972 00 00 c

ATOM 1763 OG1 THR 116 6 . 029 34.924 19.876 00 00 0

ATOM 1764 CG2 THR 116 8 . 140 33.901 19.869 00 00 c

ATOM 1765 H THR 116 5 ..408 35.587 17.162 00 00 H

ATOM 1766 HA THR 116 7 , . 896 36.401 18.594 00 00 H

ATOM 1767 HB THR 116 6 , . 599 33.617 18.385 00 00 H

ATOM 1768 HG1 THR 116 6 .419 35.672 20.340 0.00 00 H

ATOM 1769 1HG2 THR 116 7 . 749 33.164 20.594 0.00 00 H

ATOM 1770 2HG2 THR 116 8 . 916 33.391 19.273 00 00 H

ATOM 1771 3HG2 THR 116 8 . 645 34.699 20.447 00 00 H

ATOM 1772 N ILE 117 8 . 318 34.407 15.904 00 00 N

ATOM 1773 CA ILE 117 9 .352 34.029 14.882 00 00 c

ATOM 1774 C ILE 117 9 . 938 35.302 14.159 00 00 c

ATOM 1775 O ILE 117 11.156 35.448 14.121 0.00 00 0

ATOM 1776 CB ILE 117 8.849 32.926 13.872 0.00 00 c

ATOM 1777 CG2 ILE 117 9.949 32.559 12.832 0.00 00 c

ATOM 1778 CGI ILE 117 8.346 31.616 14.553 00 00 C

ATOM 1779 GDI ILE 117 7.555 30.660 13.636 00 0.00 c

ATOM 1780 H ILE 117 7.320 34.165 15.823 00 0.00 H

ATOM 1781 HA ILE 117 10.206 33.582 15.430 00 00 H

ATOM 1782 HB ILE 117 7.992 33.360 13.317 00 00 H

ATOM 1783 1HG2 ILE 117 9.638 31.755 12.143 00 00 H

ATOM 1784 2HG2 ILE 117 10.214 33.415 12.186 00 00 H

ATOM 1785 3HG2 ILE 117 10.883 32.227 13.320 00 00 H

ATOM 1786 1HG1 ILE 117 .678 31.869 15.398 00 00 H

ATOM 1787 2HG1 ILE 117 .192 31.074 15.019 00 00 H

ATOM 1788 1HD1 ILE 117 .178 29.784 14.193 00 00 H

ATOM 1789 2HD1 ILE 117 .672 31.154 13.189 00 00 H

ATOM 1790 3HD1 ILE 117 .162 30.257 12.805 00 00 H

ATOM 1791 N LYS 118 .117 36.206 13.594 00 00 N

ATOM 1792 CA LYS 118 .586 37.524 13.057 00 0.00 c

ATOM 1793 C LYS 118 10.488 38.392 14.012 00 0.00 c

ATOM 1794 0 LYS 118 11.540 38.867 13.575 00 00 0

ATOM 1795 CB LYS 118 8.313 38.272 12.574 00 00 c

ATOM 1796 CG LYS 118 8.564 39.530 11.708 00 00 C

ATOM 1797 CD LYS 118 7.335 40.449 11.572 00 00 c

ATOM 1798 CE LYS 118 6.173 39.831 10.778 0.00 00 c

ATOM 1799 NZ LYS 118 5.121 40.849 10.594 0.00 00 N

ATOM 1800 H LYS 118 8.117 36.010 13.752 00 00 H

ATOM 1801 HA LYS 118 10.207 37.309 12.166 00 00 H

ATOM 1802 1HB LYS 118 .711 38.537 13.468 00 00 H

ATOM 1803 2HB LYS 118 .668 37.580 11.995 00 00 H

ATOM 1804 1HG LYS 118 .911 39.223 10.700 00 00 H

ATOM 1805 2HG LYS 118 .395 40.124 12.138 0.00 00 H

ATOM 1806 1HD LYS 118 .673 41.383 11.078 0.00 00 H

ATOM 1807 2HD LYS 118 .000 40.762 12.584 00 00 H

ATOM 1808 1HE LYS 118 .777 38.926 11.296 00 00 H

ATOM 1809 2HE LYS 118 .537 39.447 9.792 00 00 H

ATOM 1810 1HZ LYS 118 .316 40.485 10.061 00 00 H

ATOM 1811 2HZ LYS 118 .728 41.195 11.481 00 0.00 H

ATOM 1812 3HZ LYS 118 .446 41.670 10.068 00 0.00 H

ATOM 1813 N ASP 119 10.120 38.556 15.300 00 00 N

ATOM 1814 CA ASP 119 11.024 39.147 16.328 00 00 C

ATOM 1815 C ASP 119 12.321 38.310 16.611 00 00 C

ATOM 1816 0 ASP 119 13.409 38.853 16.429 00 00 0

ATOM 1817 CB ASP 119 10.178 39.469 17.588 00 00 C ATOM 1818 CG ASP 119 10.893 40.348 18.614 00 0.00 c

ATOM 1819 OD1 ASP 119 10.774 41.566 18.662 00 0.00 0

ATOM 1820 OD2 ASP 119 11.684 39.629 19.457 00 0.00 0

ATOM 1821 H ASP 119 9.224 38.127 15.573 00 0.00 H

ATOM 1822 HA ASP 119 11.366 40.125 15.935 0.00 0.00 H

ATOM 1823 1HB ASP 119 9.846 38.540 18.087 0.00 00 H

ATOM 1824 2HB ASP 119 9.247 39.997 17.311 00 00 H

ATOM 1825 N LEU 120 12.242 37.022 17.003 00 00 N

ATOM 1826 CA LEU 120 13.442 36.138 17.159 00 00 c

ATOM 1827 C LEU 120 14.415 36.048 15.926 00 00 c

ATOM 1828 O LEU 120 15.629 36.106 16.115 00 0.00 0

ATOM 1829 CB LEU 120 12.997 34.725 17.645 00 0.00 c

ATOM 1830 CG LEU 120 12.362 34.604 19.060 00 00 c

ATOM 1831 CD1 LEU 120 11.809 33.187 19.283 00 00 c

ATOM 1832 CD2 LEU 120 13.349 34.923 20.194 00 00 c

ATOM 1833 H LEU 120 11.277 36.691 17.150 00 00 H

ATOM 1834 HA LEU 120 14.053 36.575 17.970 00 00 H

ATOM 1835 1HB LEU 120 12.291 34.318 16.895 00 00 H

ATOM 1836 2HB LEU 120 13.867 34.042 17.606 00 00 H

ATOM 1837 HG LEU 120 11.515 35.319 19.132 00 00 H

ATOM 1838 2HD1 LEU 120 11.080 32.910 18.499 00 00 H

ATOM 1839 3HD1 LEU 120 12.610 32.424 19.277 00 00 H

ATOM 1840 1HD1 LEU 120 11.288 33.105 20.255 00 00 H

ATOM 1841 2HD2 LEU 120 14.231 34.258 20.184 00 0.00 H

ATOM 1842 3HD2 LEU 120 13.715 35.966 20.140 00 0.00 H

ATOM 1843 1HD2 LEU 120 12.878 34.829 21.190 00 0.00 H

ATOM 1844 N MET 121 13.903 35.986 14.683 0.00 0.00 N

ATOM 1845 CA MET 121 14.717 36.141 13.443 0.00 00 C

ATOM 1846 C MET 121 15.524 37.474 13.286 00 00 C

ATOM 1847 O MET 121 16.732 37.404 13.043 00 00 0

ATOM 1848 CB MET 121 13.806 35.878 12.212 00 00 c

ATOM 1849 CG MET 121 13.430 34.399 11.970 00 00 c

ATOM 1850 SD MET 121 14.861 33.288 11.917 00 00 s

ATOM 1851 CE MET 121 15.974 34.100 10.758 00 00 c

ATOM 1852 H MET 121 12.873 35.933 14.663 00 00 H

ATOM 1853 HA MET 121 15.486 35.348 13.462 00 00 H

ATOM 1854 1HB MET 121 14.300 36.250 11.294 00 00 H

ATOM 1855 2HB MET 121 12.884 36.490 12.284 00 00 H

ATOM 1856 1HG MET 121 12.857 34.304 11.033 00 00 H

ATOM 1857 2HG MET 121 12.758 34.036 12.769 00 0.00 H

ATOM 1858 1HE MET 121 16.801 33.419 10.500 00 0.00 H

ATOM 1859 2HE MET 121 15.444 34.372 9.827 00 00 H

ATOM 1860 3HE MET 121 16.413 35.015 11.194 00 00 H

ATOM 1861 N ARG 122 14.909 38.666 13.427 00 00 N

ATOM 1862 CA ARG 122 15.676 39.952 13.489 00 00 c

ATOM 1863 C ARG 122 16.575 40.123 14.765 00 00 c

ATOM 1864 O ARG 122 17.577 40.839 14.708 00 00 0

ATOM 1865 CB ARG 122 14.784 41.151 13.080 00 00 c

ATOM 1866 CG ARG 122 15.593 42.382 12.594 00 00 c

ATOM 1867 CD ARG 122 14.770 43.389 11.775 00 00 c

ATOM 1868 NE ARG 122 15.442 44.713 11.788 1.00 0.00 N

ATOM 1869 CZ ARG 122 15.004 45.804 11.169 1.00 0.00 c

ATOM 1870 NH1 ARG 122 13.941 45.855 10.423 1.00 00 N

ATOM 1871 NH2 ARG 122 15.683 46.883 11.327 1.00 00 N

ATOM 1872 H ARG 122 13.921 38.579 13.711 1.00 00 H

ATOM 1873 HA ARG 122 16.418 39.870 12.673 1.00 00 H

ATOM 1874 1HB ARG 122 14.117 40.824 12.259 1.00 00 H

ATOM 1875 2HB ARG 122 14.091 41.410 13.905 1.00 00 H

ATOM 1876 1HG ARG 122 16.087 42.849 13.465 1.00 00 H

ATOM 1877 2HG ARG 122 16.430 42.040 11.953 1.00 00 H

ATOM 1878 1HD ARG 122 14.662 43.011 10.734 1.00 00 H

ATOM 1879 2HD ARG 122 13.736 43.463 12.175 1.00 00 H

ATOM 1880 HE ARG 122 16.341 44.854 12.250 1.00 00 H

ATOM 1881 2HH1 ARG 122 13.486 44.960 10.227 1.00 00 H

ATOM 1882 1HH1 ARG 122 13.745 46.730 9.932 1.00 0.00 H ATOM 1883 1HH2 ARG 122 15.,284 47.,734 10..918 1..00 0.,00 H

ATOM 1884 2HH2 ARG 122 16. 526 46. ,848 11. ,892 1. ,00 0. ,00 H

ATOM 1885 N GLN 123 16. 242 39. ,471 15. ,896 0. ,00 0. ,00 N

ATOM 1886 CA GLN 123 17. .117 39. ,416 17, ,099 0. ,00 0. ,00 C

ATOM 1887 C GLN 123 18. .432 38, .603 16, ,776 0, ,00 0. ,00 C

ATOM 1888 O GLN 123 19. ,522 39, ,075 17. .105 0, .00 0, .00 O

ATOM 1889 CB GLN 123 16. ,344 38. ,805 18, .304 0. .00 0, .00 C

ATOM 1890 CG GLN 123 15. ,107 39, .577 18, .858 0, ,00 0. .00 C

ATOM 1891 CD GLN 123 15. .138 40. .228 20. .245 0, .00 0. .00 C

ATOM 1892 OE1 GLN 123 14, .128 40. ,285 20. .937 0, .00 0, .00 O

ATOM 1893 NE2 GLN 123 16. ,234 40, .774 20, ,706 0. .00 0. .00 N

ATOM 1894 H GLN 123 15, .358 38, .935 15. ,847 0. .00 0, .00 H

ATOM 1895 HA GLN 123 17, .448 40, .430 17. .376 0. .00 0, .00 H

ATOM 1896 1HB GLN 123 17, ,043 38, ,636 19, .138 0, .00 0, .00 H

ATOM 1897 2HB GLN 123 16, .026 37, ,779 18. ,038 0, .00 0, ,00 H

ATOM 1898 1HG GLN 123 14. ,275 38, ,847 18, .933 0, .00 0. .00 H

ATOM 1899 2HG GLN 123 14, .691 40, .297 18, .139 0, ,00 0, .00 H

ATOM 1900 1HE2 GLN 123 17, .110 40, .584 20, .208 0, .00 0, .00 H

ATOM 1901 2HE2 GLN 123 16. .103 41, ,128 21. .659 0. ,00 0, .00 H

ATOM 1902 N PHE 124 18. ,365 37, .451 16. .069 1, .00 0, .00 N

ATOM 1903 CA PHE 124 19. .566 36, .799 15, .450 1, .00 0, .00 C

ATOM 1904 C PHE 124 20, .398 37, .721 14 .474 1, .00 0 .00 C

ATOM 1905 O PHE 124 21, .627 37, .772 14 .563 1, .00 0 .00 O

ATOM 1906 CB PHE 124 19. .177 35, .476 14, .709 1, .00 0, .00 C

ATOM 1907 CG PHE 124 18, .267 34, .395 15, .343 1, .00 0, .00 C

ATOM 1908 GDI PHE 124 18, .243 34, .123 16 .715 1, .00 0 .00 C

ATOM 1909 CE1 PHE 124 17, ,368 33, .165 17 .229 1 .00 0 .00 C

ATOM 1910 CZ PHE 124 16, .536 32, .448 16, .374 1, .00 0, .00 C

ATOM 1911 CE2 PHE 124 16, .570 32, .692 15 .007 1, .00 0 .00 C

ATOM 1912 CD2 PHE 124 17, .437 33, .653 14 .491 1, .00 0 .00 C

ATOM 1913 H PHE 124 17 .410 37, .091 15 .919 1 .00 0 .00 H

ATOM 1914 HA PHE 124 20, .253 36, .523 16, .274 1, .00 0, .00 H

ATOM 1915 1HB PHE 124 18, .723 35, .770 13 .742 1, .00 0, .00 H

ATOM 1916 2HB PHE 124 20, .113 34, .965 14 .413 1, .00 0 .00 H

ATOM 1917 HD1 PHE 124 18 .887 34 .665 17 .392 1, .00 0 .00 H

ATOM 1918 HE1 PHE 124 17 .338 32 .970 18 .292 1 .00 0 .00 H

ATOM 1919 HZ PHE 124 15, .861 31, .706 16. .775 1, .00 0, .00 H

ATOM 1920 HE2 PHE 124 15 .917 32, .139 14 .347 1, .00 0 .00 H

ATOM 1921 HD2 PHE 124 17 .447 33 .828 13 .425 1 .00 0 .00 H

ATOM 1922 N LEU 125 19 .722 38 .444 13 .559 0 .00 0 .00 N

ATOM 1923 CA LEU 125 20, .368 39, .370 12 .586 0, .00 0, .00 C

ATOM 1924 C LEU 125 21 .046 40 .655 13 .166 0 .00 0 .00 C

ATOM 1925 O LEU 125 22 .143 40 .978 12 .712 0 .00 0 .00 O

ATOM 1926 CB LEU 125 19 .333 39 .761 11 .495 0 .00 0 .00 C

ATOM 1927 CG LEU 125 18 .813 38, .643 10 .557 0, .00 0 .00 C

ATOM 1928 CD1 LEU 125 17 .650 39 .174 9 .705 0 .00 0 .00 C

ATOM 1929 CD2 LEU 125 19 .930 38 .127 9 .640 0 .00 0 .00 C

ATOM 1930 H LEU 125 18 .714 38 .241 13 .552 0 .00 0 .00 H

ATOM 1931 HA LEU 125 21 .189 38 .817 12 .088 0 .00 0 .00 H

ATOM 1932 1HB LEU 125 19 .776 40 .549 10 .853 0 .00 0 .00 H

ATOM 1933 2HB LEU 125 18 .483 40 .264 11 .989 0 .00 0 .00 H

ATOM 1934 HG LEU 125 18 .432 37 .793 11 .160 0 .00 0 .00 H

ATOM 1935 1HD1 LEU 125 17 .265 38 .405 9 .008 0 .00 0 .00 H

ATOM 1936 2HD1 LEU 125 16, .795 39 .476 10 .334 0, .00 0, .00 H

ATOM 1937 3HD1 LEU 125 17 .937 40 .052 9 .095 0, .00 0, .00 H

ATOM 1938 1HD2 LEU 125 19 .556 37 .398 8 .904 0, .00 0 .00 H

ATOM 1939 2HD2 LEU 125 20 .414 38 .945 9 .075 0, .00 0 .00 H

ATOM 1940 3HD2 LEU 125 20, .726 37, .611 10, .208 0, ,00 0, .00 H

ATOM 1941 N ARG 126 20, .452 41, .392 14, .127 0, .00 0, .00 N

ATOM 1942 CA ARG 126 21, .141 42, .551 14, .783 0, .00 0, .00 C

ATOM 1943 C ARG 126 22 .443 42 .201 15, .592 0, .00 0, .00 C

ATOM 1944 O ARG 126 23 .419 42 .950 15, .513 0, .00 0, .00 O

ATOM 1945 CB ARG 126 20, .148 43, .389 15, .635 0. .00 0, .00 C

ATOM 1946 CG ARG 126 19, .031 44, .133 14, .854 0. .00 0, .00 C

ATOM 1947 CD ARG 126 18, .395 45, .309 15, .626 0, .00 0, .00 C ri l / D tVU-i / \_ι U -

93

ATOM 1948 NE ARG 126 19. .314 46, .485 15, ,614 0. .00 0, .00 N

ATOM 1949 CZ ARG 126 19. ,253 47. ,512 14. .774 0. .00 0, .00 C

ATOM 1950 NH1 ARG 126 18. ,337 47, ,666 13. .863 0, .00 0, .00 N

ATOM 1951 NH2 ARG 126 20. .161 48, ,417 14, .878 0, ,00 0, .00 N

ATOM 1952 H ARG 126 19. .560 40, ,994 14. .450 0. .00 0 .00 H

ATOM 1953 HA ARG 126 21, .504 43, .218 13, .972 0. .00 0 .00 H

ATOM 1954 1HB ARG 126 20. ,747 44, ,140 16. .187 0, .00 0, .00 H

ATOM 1955 2HB ARG 126 19. ,708 42. .750 16. .425 0, ,00 0, .00 H

ATOM 1956 1HG ARG 126 18, .259 43. ,396 14. .563 0, .00 0 .00 H

ATOM 1957 2HG ARG 126 19. .438 44, .498 13, .886 0, .00 0 .00 H

ATOM 1958 1HD ARG 126 18. .195 45. ,018 16. ,678 0, .00 0, .00 H

ATOM 1959 2HD ARG 126 17. .391 45, ,556 15, .225 0, .00 0 .00 H

ATOM 1960 HE ARG 126 20. .100 46, .578 16, .265 1, .00 0 .00 H

ATOM 1961 1HH1 ARG 126 18, .340 48, .606 13, .440 0, .00 0 .00 H

ATOM 1962 2HH1 ARG 126 17, .537 47. ,067 14, .032 0. .00 0, .00 H

ATOM 1963 1HH2 ARG 126 20. .040 49. .280 14, .322 0. .00 0. .00 H

ATOM 1964 2HH2 ARG 126 20. .857 48, .327 15, .616 0. .00 0 .00 H

ATOM 1965 N GLY 127 22, .482 41, .072 16, .326 0, .00 0 .00 N

ATOM 1966 CA GLY 127 23, .757 40, .505 16, .864 0, ,00 0, .00 C

ATOM 1967 C GLY 127 24, .843 40, .093 15, .839 0, .00 0 .00 C

ATOM 1968 O GLY 127 26, .001 40, .477 15 .993 0, .00 0 .00 O

ATOM 1969 H GLY 127 21, .633 40, .500 16 .228 0, .00 0 .00 H

ATOM 1970 1HA GLY 127 23, .532 39 .616 17 .483 0 .00 0 .00 H

ATOM 1971 2HA GLY 127 24, .212 41, .227 17, .570 0, .00 0 .00 H

ATOM 1972 N LEU 128 24, .470 39, .353 1 .784 0, .00 0 .00 N

ATOM 1973 CA LEU 128 25 .382 39 .065 13 .637 0 .00 0 .00 C

ATOM 1974 C LEU 128 25 .851 40 .304 12 .786 0 .00 0 .00 C

ATOM 1975 O LEU 128 27, .028 40, .372 12, .438 0, .00 0 .00 O

ATOM 1976 CB LEU 128 24, .709 37, .951 12 .787 0, .00 0 .00 C

ATOM 1977 CG LEU 128 25 .628 37 .248 11 .755 0, .00 0 .00 C

ATOM 1978 CD1 LEU 128 26 .682 36 .355 12 .432 0 .00 0 .00 C

ATOM 1979 CD2 LEU 128 24, .787 36, .403 10 .789 0, .00 0 .00 C

ATOM 1980 H LEU 128 23, .474 39, .103 14 .766 0, .00 0 .00 H

ATOM 1981 HA LEU 128 26 .309 38, .640 14 .068 0, .00 0 .00 H

ATOM 1982 1HB LEU 128 23 .837 38 .397 12 .270 0 .00 0 .00 H

ATOM 1983 2HB LEU 128 24 .271 37 .172 13 .444 0 .00 0 .00 H

ATOM 1984 HG LEU 128 26 .154 38, .018 11 .153 0, .00 0 .00 H

ATOM 1985 1HD1 LEU 128 27 .304 35, .817 11 .695 0, .00 0 .00 H

ATOM 1986 2HD1 LEU 128 27 .389 36 .940 13 .046 0 .00 0 .00 H

ATOM 1987 3HD1 LEU 128 26 .228 35 .589 13 .089 0 .00 0 .00 H

ATOM 1988 1HD2 LEU 128 25 .410 35, .937 10 .004 0, .00 0 .00 H

ATOM 1989 2HD2 LEU 128 24 .261 35, .581 11 .310 0, .00 0 .00 H

ATOM 1990 3HD2 LEU 128 24 .022 37 .009 10 .269 0, .00 0 .00 H

ATOM 1991 N ASP 129 24 .981 41 .290 12 .491 0 .00 0 .00 N

ATOM 1992 CA ASP 129 25 .387 42, .623 11 .946 0, .00 0, .00 C

ATOM 1993 C ASP 129 26 .440 43, .427 12 .798 0, .00 0, .00 C

ATOM 1994 O ASP 129 27 .403 43, .939 12 .227 0, .00 0 .00 O

ATOM 1995 CB ASP 129 24 .065 43 .396 11 .680 0 .00 0 .00 C

ATOM 1996 CG ASP 129 24 .203 44 .723 10 .941 0 .00 0 .00 C

ATOM 1997 OD1 ASP 129 24 .815 44, .867 9 .890 0, .00 0, .00 O

ATOM 1998 OD2 ASP 129 23 .564 45, .739 11 .581 0, .00 0, .00 O

ATOM 1999 H ASP 129 24 .011 41, .115 12 .784 0, .00 0, .00 H

ATOM 2000 HA ASP 129 25 .863 42 .449 10 .961 0, .00 0 .00 H

ATOM 2001 1HB ASP 129 23 .534 43, .572 12, .634 0, .00 0, ,00 H

ATOM 2002 2HB ASP 129 23 .375 42, .786 11, .070 0, .00 0, .00 H

ATOM 2003 N PHE 130 26 .303 43, .496 14 .137 0, .00 0, .00 N

ATOM 2004 CA PHE 130 27 .404 43, .931 15 .052 0, .00 0, .00 C

ATOM 2005 C PHE 130 28, .762 43, .139 14, .942 0, .00 0, .00 C

ATOM 2006 O PHE 130 29 .819 43, .768 14, .856 0, ,00 0. .00 O

ATOM 2007 CB PHE 130 26 .776 43, .940 16, .477 0, .00 0. .00 C

ATOM 2008 CG PHE 130 27 .684 44, .398 17, .629 0. ,00 0, ,00 C

ATOM 2009 CD1 PHE 130 28 .111 45, .729 17, .714 0. .00 0, ,00 C

ATOM 2010 CE1 PHE 130 28, .945 46. .133 18. ,750 0. ,00 0, ,00 C

ATOM 2011 CZ PHE 130 29, .357 45, ,215 19. .714 0. ,00 0, ,00 C

ATOM 2012 CE2 PHE 130 28, .924 43, ,893 19. ,646 0. ,00 0, ,00 C ATOM 2013 CD2 PHE 130 28.095 43 484 18.607 0.00 00 c

ATOM 2014 H PHE 130 25.435 43 059 14.469 0.00 00 H

ATOM 2015 HA PHE 130 27.649 44 980 14.791 00 00 H

ATOM 2016 1HB PHE 130 26.366 42 ,936 16.705 00 00 H

ATOM 2017 2HB PHE 130 25.880 44 590 16.477 00 00 H

ATOM 2018 HD1 PHE 130 27.797 46 451 16.972 0.00 0.00 H

ATOM 2019 HE1 PHE 130 29.273 47.161 18.810 0.00 0.00 H

ATOM 2020 HZ PHE 130 30.004 45 526 20.521 00 0.00 H

ATOM 2021 HE2 PHE 130 29.242 43 ,189 20.399 00 0.00 H

ATOM 2022 HD2 PHE 130 27.773 42 ,454 18.561 00 00 H

ATOM 2023 N LEU 131 28.744 41 794 14.909 00 00 N

ATOM 2024 CA LEU 131 29.952 40 ,970 14.599 00 00 c

ATOM 2025 C LEU 131 30.566 41 ,204 13.171 00 00 c

ATOM 2026 o LEU 131 31.749 41 ,532 13.070 00 00 0

ATOM 2027 CB LEU 131 29.636 39 ,467 14.870 0.00 00 c

ATOM 2028 CG LEU 131 29.206 39 ,042 16.300 0.00 00 c

ATOM 2029 CD1 LEU 131 28.896 37 ,537 16.355 0.00 00 c

ATOM 2030 CD2 LEU 131 30.264 39 ,373 17.361 0.00 00 c

ATOM 2031 H LEU 131 27.800 41 ,393 14.974 00 0.00 H

ATOM 2032 HA LEU 131 30.752 41 ,268 15.304 00 0.00 H

ATOM 2033 1HB LEU 131 30.525 38 ,870 14.592 00 00 H

ATOM 2034 2HB LEU 131 28.857 39 ,141 14.153 00 00 H

ATOM 2035 HG LEU 131 28.278 39 ,586 16.564 00 00 H

ATOM 2036 1HD1 LEU 131 28.553 37 ,225 17.361 00 00 H

ATOM 2037 2HD1 LEU 131 28.092 37 ,262 15.647 00 00 H

ATOM 2038 3HD1 LEU 131 29.780 36 ,919 16.107 00 00 H

ATOM 2039 1HD2 LEU 131 29.934 39 ,062 18.369 00 00 H

ATOM 2040 2HD2 LEU 131 31.230 38 ,876 17.160 00 00 H

ATOM 2041 3HD2 LEU 131 30.453 40 ,460 17.423 00 00 H

ATOM 2042 N HIS 132 29.778 41 ,097 12.087 00 00 N

ATOM 2043 CA HIS 132 30.242 41 ,357 10.689 00 00 c

ATOM 2044 C HIS 132 30.772 42.800 10.378 00 00 c

ATOM 2045 O HIS 132 31.807 42.928 9.719 00 00 o

ATOM 2046 CB HIS 132 29.096 40.944 9.719 00 00 c

ATOM 2047 CG HIS 132 28.760 39 ,456 9.557 00 00 c

ATOM 2048 ND1 HIS 132 27.804 39.032 8.646 00 00 N

ATOM 2049 CE1 HIS 132 27.933 37 ,676 8.805 00 00 c

ATOM 2050 NE2 HIS 132 28.843 37 ,172 9.690 00 0.00 N

ATOM 2051 CD2 HIS 132 29.368 38.348 10.183 00 0.00 c

ATOM 2052 H HIS 132 28.792 40 ,878 12.303 00 00 H

ATOM 2053 HA HIS 132 31.105 40.690 10.494 00 00 H

ATOM 2054 1HB HIS 132 29.332 41.320 8.707 00 00 H

ATOM 2055 2HB HIS 132 28.167 41.482 9.995 00 00 H

ATOM 2056 HE1 HIS 132 27.307 37.003 8.232 00 00 H

ATOM 2057 HE2 HIS 132 29.034 36.188 9.949 00 00 H

ATOM 2058 HD2 HIS 132 30.141 38.409 10.938 00 00 H

ATOM 2059 N ALA 133 30.113 43.872 10.861 00 00 N

ATOM 2060 CA ALA 133 30.681 45.250 10.844 00 0.00 C

ATOM 2061 C ALA 133 32.018 45.485 11.640 00 0.00 C

ATOM 2062 O ALA 133 32.898 46.191 11.144 00 0.00 0

ATOM 2063 CB ALA 133 29.546 46.177 11.316 00 0.00 C

ATOM 2064 H ALA 133 29.241 43.656 11.371 00 0.00 H

ATOM 2065 HA ALA 133 30.902 45.515 9.791 00 0.00 H

ATOM 2066 2HB ALA 133 28.631 46.069 10.701 00 0.00 H

ATOM 2067 3HB ALA 133 29.247 45.970 12.362 1.00 0.00 H

ATOM 2068 1HB ALA 133 29.838 47.242 11.267 00 0.00 H

ATOM 2069 N ASN 134 32.206 44.862 12.819 00 00 N

ATOM 2070 CA ASN 134 33.541 44.787 13.499 00 00 C

ATOM 2071 C ASN 134 34.527 43.656 12.986 00 00 C

ATOM 2072 O ASN 134 35.422 43.241 13.727 00 00 O

ATOM 2073 CB ASN 134 33.245 44.651 15.024 00 00 c

ATOM 2074 CG ASN 134 32.723 45 ,903 15.738 00 00 C

ATOM 2075 OD1 ASN 134 33.466 46.816 16.070 1.00 00 0

ATOM 2076 ND2 ASN 134 31.454 45 ,985 16.040 1.00 0.00 N

ATOM 2077 H ASN 134 31.405 44.279 13.103 1.00 0.00 H ATOM 2078 HA ASN 134 34.092 45.736 13.346 00 0.00 H

ATOM 2079 1HB ASN 134 32.580 43.785 15.214 00 0.00 H

ATOM 2080 2HB ASN 134 34.174 44.388 15.560 00 ,00 H

ATOM 2081 1HD2 ASN 134 31.181 46.832 16.542 00 .00 H

ATOM 2082 2HD2 ASN 134 30.853 45.212 15.722 00 .00 H

ATOM 2083 N CYS 135 34.406 43.169 11.732 00 .00 N

ATOM 2084 CA CYS 135 35.248 42.075 11.148 00 ,00 c

ATOM 2085 C CYS 135 35.368 40.693 11.910 00 .00 C

ATOM 2086 o CYS 135 36.355 39.967 11.753 00 ,00 0

ATOM 2087 CB CYS 135 36.601 42.689 10.710 00 ,00 C

ATOM 2088 SG CYS 135 36.377 44.165 9.652 00 ,00 s

ATOM 2089 H CYS 135 33.608 43.575 11.227 1.00 .00 H

ATOM 2090 HA CYS 135 34.735 41.786 10.212 1.00 .00 H

ATOM 2091 1HB CYS 135 37.194 42.971 11.601 1.00 0.00 H

ATOM 2092 2HB CYS 135 37.209 41.945 10.164 00 0.00 H

ATOM 2093 HG CYS 135 35.792 43.545 8.630 00 00 H

ATOM 2094 N ILE 136 34.333 40.288 12.666 00 00 N

ATOM 2095 CA ILE 136 34.311 39.007 13.433 00 00 c

ATOM 2096 C ILE 136 33.333 38.032 12.698 00 00 c

ATOM 2097 o ILE 136 32.106 38.158 12.762 00 00 0

ATOM 2098 CB ILE 136 33.962 39.246 14.950 00 00 c

ATOM 2099 CGI ILE 136 34.940 40.191 15.713 00 00 c

ATOM 2100 CG2 ILE 136 33.793 37.936 15.770 00 00 c

ATOM 2101 GDI ILE 136 36.419 39.763 15.802 00 00 c

ATOM 2102 H ILE 136 33.566 40.973 12.740 00 00 H

ATOM 2103 HA ILE 136 35.321 38.548 13.440 00 00 H

ATOM 2104 HB ILE 136 32.973 39.748 14.967 00 00 H

ATOM 2105 1HG1 ILE 136 34.898 41.196 15.249 00 00 H

ATOM 2106 2HG1 ILE 136 34.560 40.360 16.738 00 0.00 H

ATOM 2107 2HG2 ILE 136 32.966 37.310 15.384 00 0.00 H

ATOM 2108 3HG2 ILE 136 34.709 37.319 15.749 00 .00 H

ATOM 2109 1HG2 ILE 136 33.558 38.139 16.832 00 .00 H

ATOM 2110 2HD1 ILE 136 36.552 38.771 16.273 00 .00 H

ATOM 2111 3HD1 ILE 136 36.900 39.718 14.807 00 ,00 H

ATOM 2112 1HD1 ILE 136 37.007 40.478 16.404 00 .00 H

ATOM 2113 N VAL 137 33.895 37.012 12.034 00 ,00 N

ATOM 2114 CA VAL 137 33.100 35.882 11.468 00 ,00 c

ATOM 2115 C VAL 137 32.859 34.833 12.611 00 ,00 c

ATOM 2116 O VAL 137 33.802 34.199 13.093 00 ,00 0

ATOM 2117 CB VAL 137 33.802 35.272 10.200 00 0.00 c

ATOM 2118 CGI VAL 137 32.982 34.143 9.533 00 0.00 c

ATOM 2119 CG2 VAL 137 34.091 36.298 9.078 00 0.00 c

ATOM 2120 H VAL 137 34.918 37.030 12.039 00 ,00 H

ATOM 2121 HA VAL 137 32.114 36.260 11.122 0.00 ,00 H

ATOM 2122 HB VAL 137 34.770 34.846 10.528 0.00 ,00 H

ATOM 2123 1HG1 VAL 137 33.487 33.698 8.655 00 ,00 H

ATOM 2124 2HG1 VAL 137 32.753 33.318 10.232 00 ,00 H

ATOM 2125 3HG1 VAL 137 31.997 34.512 9.180 00 0.00 H

ATOM 2126 1HG2 VAL 137 34.567 35.841 8.191 00 0.00 H

ATOM 2127 2HG2 VAL 137 33.163 36.789 8.732 00 00 H

ATOM 2128 3HG2 VAL 137 34.763 37.107 9.418 0.00 00 H

ATOM 2129 N HIS 138 31.592 34.637 13.030 0.00 00 N

ATOM 2130 CA HIS 138 31.224 33.591 14.042 00 00 C

ATOM 2131 C HIS 138 31.687 32.122 13.683 00 00 C

ATOM 2132 O HIS 138 32.304 31.462 14.524 00 00 O

ATOM 2133 CB HIS 138 29.701 33.787 14.338 00 00 C

ATOM 2134 CG HIS 138 29.073 33.032 15.516 00 00 C

ATOM 2135 ND1 HIS 138 29.283 31.691 15.788 00 00 N

ATOM 2136 CΞ1 HIS 138 28.478 31.543 16.886 00 00 C

ATOM 2137 NE2 HIS 138 27.744 32.605 17.335 00 00 N

ATOM 2138 CD2 HIS 138 28.139 33.571 16.425 00 00 C

ATOM 2139 H HIS 138 30.871 35.143 12.497 00 00 H

ATOM 2140 HA HIS 138 31.756 33.843 14.979 00 00 H

ATOM 2141 1HB HIS 138 29.120 33.518 13.438 00 00 H

ATOM 2142 2HB HIS 138 29.489 34.864 14.480 00 00 H ATOM 2143 HE1 HIS 138 28.432 30.588 17.401 00 .00 H

ATOM 2144 HE2 HIS 138 27.157 32.633 18.177 00 ,00 H

ATOM 2145 HD2 HIS 138 27.788 34.594 16.413 00 ,00 H

ATOM 2146 N ARG 139 31.434 31.645 12.444 00 .00 N

ATOM 2147 CA ARG 139 31.885 30.310 11.930 00 0.00 c

ATOM 2148 C ARG 139 30.934 29.142 12.339 00 0.00 c

ATOM 2149 O ARG 139 30.360 28.477 11.474 0.00 00 0

ATOM 2150 CB ARG 139 33.397 29.955 12.106 0.00 00 c

ATOM 2151 CG ARG 139 34.412 30.932 11.467 00 00 c

ATOM 2152 CD ARG 139 35.863 30.494 11.715 00 00 c

ATOM 2153 NE ARG 139 36.784 31.387 10.962 00 00 N

ATOM 2154 CZ ARG 139 38.090 31.501 11.177 00 00 c

ATOM 2155 NH1 ARG 139 38.748 30.829 12.074 00 00 N

ATOM 2156 NH2 ARG 139 38.744 32.325 10.438 00 00 N

ATOM 2157 H ARG 139 30.674 32.176 11.978 00 0.00 H

ATOM 2158 HA ARG 139 31.728 30.390 10.837 00 0.00 H

ATOM 2159 1HB ARG 139 33.558 28.943 11.689 00 00 H

ATOM 2160 2HB ARG 139 33.605 29.852 13.189 00 00 H

ATOM 2161 1HG ARG 139 34.239 31.948 11.884 00 00 H

ATOM 2162 2HG ARG 139 34.182 31.022 10.387 0.00 00 H

ATOM 2163 1HD ARG 139 35.999 29.435 11.412 0.00 00 H

ATOM 2164 2HD ARG 139 36.044 30.540 12.812 00 00 H

ATOM 2165 HE ARG 139 36.404 32.115 10.342 00 00 H

ATOM 2166 1HH1 ARG 139 39.726 31.090 12.197 00 00 H

ATOM 2167 2HH1 ARG 139 38.132 30.320 12.711 00 0.00 H

ATOM 2168 1HH2 ARG 139 39.740 32.458 10.621 00 0.00 H

ATOM 2169 2HH2 ARG 139 38.197 32.868 9.762 00 00 H

ATOM 2170 N ASP 140 30.775 28.890 13.646 00 00 N

ATOM 2171 CA ASP 140 29.943 27.774 14.171 00 0.00 c

ATOM 2172 C ASP 140 28.575 28.278 14.759 00 0.00 c

ATOM 2173 O ASP 140 28.324 28.162 15.960 00 .00 o

ATOM 2174 CB ASP 140 30.902 27.051 15.160 00 00 c

ATOM 2175 CG ASP 140 30.460 25.667 15.604 00 ,00 c

ATOM 2176 OD1 ASP 140 30.217 24.751 14.829 00 ,00 o

ATOM 2177 OD2 ASP 140 30.426 25.541 16.956 00 ,00 o

ATOM 2178 H ASP 140 31.127 29.639 14.260 00 ,00 H

ATOM 2179 HA ASP 140 29.692 27.058 13.365 00 ,00 H

ATOM 2180 1HB ASP 140 31.060 27.684 16.056 00 ,00 H

ATOM 2181 2HB ASP 140 31.907 26.910 14.724 00 ,00 H

ATOM 2182 N LEU 141 27.676 28.815 13.913 00 ,00 N

ATOM 2183 CA LEU 141 26.376 29.402 14.363 00 ,00 c

ATOM 2184 C LEU 141 25.228 28.333 14.403 00 ,00 c

ATOM 2185 O LEU 141 24.687 27.937 13.366 00 0.00 0

ATOM 2186 CB LEU 141 26.100 30.627 13.443 00 0.00 c

ATOM 2187 CG LEU 141 24.804 31.438 13.707 00 00 c

ATOM 2188 GDI LEU 141 24.723 32.035 15.122 00 00 c

ATOM 2189 CD2 LEU 141 24.699 32.582 12.690 00 00 c

ATOM 2190 H LEU 141 28.067 29.053 12.995 00 00 H

ATOM 2191 HA LEU 141 26.501 29.814 15.387 00 00 H

ATOM 2192 1HB LEU 141 26.094 30.291 12.387 00 00 H

ATOM 2193 2HB LEU 141 26.966 31.320 13.504 0.00 00 H

ATOM 2194 HG LEU 141 23.930 30.770 13.561 0.00 00 H

ATOM 2195 1HD1 LEU 141 23.784 32.600 15.270 00 00 H

ATOM 2196 2HD1 LEU 141 24.744 31.258 15.908 00 00 H

ATOM 2197 3HD1 LEU 141 25.560 32.728 15.328 00 00 H

ATOM 2198 1HD2 LEU 141 23.784 33.183 12.838 0.00 00 H

ATOM 2199 2HD2 LEU 141 25.558 33.275 12.761 0.00 00 H

ATOM 2200 3HD2 LEU 141 24.676 32.208 11.650 00 00 H

ATOM 2201 N LYS 142 24.895 27.833 15.606 00 00 N

ATOM 2202 CA LYS 142 24.031 26.624 15.789 00 00 C

ATOM 2203 C LYS 142 23.038 26.791 17.005 00 00 C

ATOM 2204 O LYS 142 23.446 27.386 18.008 00 00 O

ATOM 2205 CB LYS 142 24.940 25.364 15.964 00 00 c

ATOM 2206 CG LYS 142 25.778 25.014 14.710 00 00 c

ATOM 2207 CD LYS 142 26.603 23.721 14.788 00 00 c ATOM 2208 CE LYS 142 27..324 23.,487 13..450 0.,00 0.,00 c

ATOM 2209 NZ LYS 142 28. .259 22. ,356 13, .569 0. ,00 0. ,00 N

ATOM 2210 H LYS 142 25. ,380 28. ,271 16. .406 0. ,00 0. ,00 H

ATOM 2211 HA LYS 142 23. ,417 26. ,485 14, ,881 0. ,00 0. ,00 H

ATOM 2212 1HB LYS 142 24, .302 24. .500 16. .230 0. .00 0. ,00 H

ATOM 2213 2HB LYS 142 25. ,603 25. .510 16. .841 0. ,00 0, ,00 H

ATOM 2214 1HG LYS 142 26. .472 25. .861 14. .526 0, .00 0. ,00 H

ATOM 2215 2HG LYS 142 25. .105 25, .013 13. .832 0, .00 0, ,00 H

ATOM 2216 1HD LYS 142 25. .951 22, .865 15, .056 0, ,00 0, ,00 H

ATOM 2217 2HD LYS 142 27. .328 23. .824 15. .626 0, ,00 0. ,00 H

ATOM 2218 1HE LYS 142 27. .865 24, ,423 13, .176 0, ,00 0. .00 H

ATOM 2219 2HE LYS 142 26. .579 23. ,324 12, .639 0, .00 0, .00 H

ATOM 2220 1HZ LYS 142 28. .745 22. .059 12. ,720 1, .00 0. ,00 H

ATOM 2221 2HZ LYS 142 28, ,950 22. ,546 14. .311 1, .00 0, .00 H

ATOM 2222 3HZ LYS 142 27, .781 21. .499 13. .908 1, ,00 0, .00 H

ATOM 2223 N PRO 143 21, .772 26. .258 17, .029 0, .00 0, .00 N

ATOM 2224 CA PRO 143 20, .819 26, ,445 18. .174 0, .00 0, .00 C

ATOM 2225 CD PRO 143 21, .155 25, .556 15, .884 0, .00 0. .00 C

ATOM 2226 C PRO 143 21, .274 26, .237 19, .662 0, .00 0, .00 C

ATOM 2227 O PRO 143 20, .878 27. .003 20, .540 0, .00 0, .00 O

ATOM 2228 CB PRO 143 19, .651 25. .523 17, .767 0, .00 0, .00 C

ATOM 2229 CG PRO 143 19, .669 25, .515 16, .241 0, .00 0, .00 c

ATOM 2230 HA PRO 143 20, .467 27, .494 18 .124 0, .00 0, .00 H

ATOM 2231 1HD PRO 143 21, .566 24, .533 15, .791 0, ,00 0. ,00 H

ATOM 2232 2HD PRO 143 21, .296 26, .072 14 .915 0, .00 0, .00 H

ATOM 2233 1HB PRO 143 18 .683 25 .871 18 .178 0, .00 0, .00 H

ATOM 2234 2HB PRO 143 19, .801 24 , .497 18 .154 0, .00 0. .00 H

ATOM 2235 1HG PRO 143 19 .151 26, .415 15 .856 0, .00 0, .00 H

ATOM 2236 2HG PRO 143 19 .144 24 .641 15 .808 0, .00 0, .00 H

ATOM 2237 N GLU 144 22, .134 25, .249 19, .949 1, .00 0, .00 N

ATOM 2238 CA GLU 144 22 .786 25, .100 21 .289 1, .00 0, .00 C

ATOM 2239 C GLU 144 23 .710 26 .295 21 .756 1, .00 0, .00 C

ATOM 2240 O GLU 144 23 .714 26 .623 22 .945 1 .00 0, .00 O

ATOM 2241 CB GLU 144 23 .504 23, .722 21 .256 1, .00 0, .00 C

ATOM 2242 CG GLU 144 24 .083 23 .197 22 .600 1, .00 0, .00 C

ATOM 2243 CD GLU 144 23 .092 22 .664 23 .638 1 .00 0, .00 C

ATOM 2244 OE1 GLU 144 21 .905 22 .435 23 .430 1, .00 0, .00 O

ATOM 2245 OE2 GLU 144 23 .699 22 .429 24 .832 1 .00 0, .00 O

ATOM 2246 H GLU 144 22 .426 24 .708 19 .136 1 .00 0 .00 H

ATOM 2247 HA GLU 144 21 .983 25 .019 22 .052 1 .00 0 .00 H

ATOM 2248 1HB GLU 144 22 .803 22 .949 20 .883 1, .00 0, .00 H

ATOM 2249 2HB GLU 144 24 .323 23 .767 20 .515 1 .00 0, .00 H

ATOM 2250 1HG GLU 144 24 .785 22 .369 22 .431 1 .00 0 .00 H

ATOM 2251 2HG GLU 144 24 .662 23 .981 23 .119 1, .00 0, .00 H

ATOM 2252 N ASN 145 24 .461 26 .950 20 .846 0, .00 0, .00 N

ATOM 2253 CA ASN 145 25 .109 28 .275 21 .118 0 .00 0, .00 C

ATOM 2254 C ASN 145 24 .291 29 .582 20 .776 0, .00 0, .00 C

ATOM 2255 O ASN 145 24 .866 30 .672 20 .722 0, .00 0, .00 O

ATOM 2256 CB ASN 145 26 .536 28 .239 20 .503 0. .00 0 .00 C

ATOM 2257 CG ASN 145 26 .677 28 .171 18 .976 0, .00 0 .00 C

ATOM 2258 OD1 ASN 145 26 .229 29 .023 18. .218 0, .00 0, .00 O

ATOM 2259 ND2 ASN 145 27 .354 27 .177 18 .468 0, .00 0, .00 N

ATOM 2260 H ASN 145 24 .211 26 .680 19 .888 0, .00 0, ,00 H

ATOM 2261 HA ASN 145 25 .274 28 .367 22, .211 0, .00 0. .00 H

ATOM 2262 1HB ASN 145 27 .108 27 .425 20, .989 0, .00 0, .00 H

ATOM 2263 2HB ASN 145 27 .072 29 .147 20 .826 0, ,00 0, .00 H

ATOM 2264 1HD2 ASN 145 27 .864 26 .627 19 .161 0, .00 0, .00 H

ATOM 2265 2HD2 ASN 145 27 .665 27 .389 17, .509 0. .00 0, .00 H

ATOM 2266 N ILE 146 22 .958 29 .510 20, .636 0. .00 0, .00 N

ATOM 2267 CA ILE 146 22 .060 30 .704 20, .604 0, .00 0, .00 C

ATOM 2268 C ILE 146 21 .246 30, .662 21. .938 0, ,00 0. .00 C

ATOM 2269 O ILE 146 20 .442 29, .756 22. .172 0, ,00 0. .00 O

ATOM 2270 CB ILE 146 21 .190 30 .749 19, .297 0, .00 0, .00 C

ATOM 2271 CG2 ILE 146 20. .171 31, .920 19. ,333 0. ,00 0. .00 C

ATOM 2272 CGI ILE 146 22 .067 30, .863 18. .012 0. ,00 0, .00 C ATOM 2273 CD1 ILE 146 21.329 30.744 16.669 0.00 0.00 c

ATOM 2274 H ILE 146 22.584 28.559 20.768 0.00 0.00 H

ATOM 2275 HA ILE 146 22.659 31.637 20.599 00 0.00 H

ATOM 2276 HB ILE 146 20.620 29.798 19.246 00 0.00 H

ATOM 2277 1HG2 ILE 146 19.525 31.920 18.441 00 0.00 H

ATOM 2278 2HG2 ILE 146 19.484 31.848 20.198 00 0.00 H

ATOM 2279 3HG2 ILE 146 20.664 32.908 19.387 00 00 H

ATOM 2280 1HG1 ILE 146 22.838 30.067 18.029 00 00 H

ATOM 2281 2HG1 ILE 146 22.648 31.804 18.036 00 00 H

ATOM 2282 1HD1 ILE 146 22.049 30.746 15.831 0.00 00 H

ATOM 2283 2HD1 ILE 146 20.754 29.801 16.604 0.00 00 H

ATOM 2284 3HD1 ILE 146 20.626 31.579 16.492 00 00 H

ATOM 2285 N LEU 147 21.482 31.636 22.825 00 00 N

ATOM 2286 CA LEU 147 20.972 31.598 24.218 00 00 c

ATOM 2287 C LEU 147 19.669 32.449 24.360 00 00 c

ATOM 2288 0 LEU 147 19.659 33.639 24.041 00 00 0

ATOM 2289 CB LEU 147 22.109 32.057 25.172 00 00 c

ATOM 2290 CG LEU 147 23.470 31.305 25.137 00 00 c

ATOM 2291 GDI LEU 147 24.450 31.943 26.134 00 00 c

ATOM 2292 CD2 LEU 147 23.339 29.802 25.434 00 00 c

ATOM 2293 H LEU 147 22.219 32.300 22.557 0.00 00 H

ATOM 2294 HA LEU 147 20.742 30.555 24.511 0.00 0.00 H

ATOM 2295 1HB LEU 147 21.709 31.974 26.195 ,00 0.00 H

ATOM 2296 2HB LEU 147 22.289 33.137 25.016 ,00 00 H

ATOM 2297 HG LEU 147 23.903 31.411 24.122 0.00 00 H

ATOM 2298 1HD1 LEU 147 25.441 31.454 26.095 0.00 00 H

ATOM 2299 2HD1 LEU 147 24.608 33.017 25.925 0.00 00 H

ATOM 2300 3HD1 LEU 147 24.092 31.857 27.177 00 00 H

ATOM 2301 1HD2 LEU 147 24.316 29.289 25.430 00 00 H

ATOM 2302 2HD2 LEU 147 22.840 29.606 26.394 00 00 H

ATOM 2303 3HD2 LEU 147 22.732 29.285 24.666 00 0.00 H

ATOM 2304 N VAL 148 18.565 31.839 24.808 00 0.00 N

ATOM 2305 CA VAL 148 17.229 32.503 24.894 0.00 00 c

ATOM 2306 C VAL 148 16.873 32.721 26.403 0.00 00 c

ATOM 2307 0 VAL 148 16.767 31.779 27.195 00 00 o

ATOM 2308 CB VAL 148 16.155 31.675 24.099 00 00 c

ATOM 2309 CGI VAL 148 14.728 32.269 24.188 00 00 c

ATOM 2310 CG2 VAL 148 16.476 31.534 22.590 00 00 c

ATOM 2311 H VAL 148 18.728 30.911 25.230 00 00 H

ATOM 2312 HA VAL 148 17.264 33.495 24.397 00 00 H

ATOM 2313 HB VAL 148 16.122 30.656 24.539 0.00 00 H

ATOM 2314 1HG1 VAL 148 13.987 31.656 23.639 0.00 00 H

ATOM 2315 2HG1 VAL 148 14.367 32.313 25.234 00 00 H

ATOM 2316 3HG1 VAL 148 14.672 33.297 23.784 00 00 H

ATOM 2317 1HG2 VAL 148 15.723 30.918 22.064 00 00 H

ATOM 2318 2HG2 VAL 148 16.527 32.512 22.078 00 00 H

ATOM 2319 3HG2 VAL 148 17.449 31.030 22.428 00 00 H

ATOM 2320 N THR 149 16.661 33.988 26.784 0.00 00 N

ATOM 2321 CA THR 149 16.172 34.363 28.149 0.00 00 C

ATOM 2322 c THR 149 14.666 33.984 28.404 0.00 00 C

ATOM 2323 0 THR 149 13.868 33.879 27.466 0.00 0.00 O

ATOM 2324 CB THR 149 16.385 35.897 28.381 ,00 0.00 C

ATOM 2325 OG1 THR 149 15.695 36.656 27.394 .00 00 0

ATOM 2326 CG2 THR 149 17.839 36.398 28.395 .00 00 c

ATOM 2327 H THR 149 16.814 34.675 26.039 .00 00 H

ATOM 2328 HA THR 149 16.772 33.813 28.904 .00 00 H

ATOM 2329 HB THR 149 15.956 36.157 29.370 .00 00 H

ATOM 2330 HG1 THR 149 16.118 36.438 26.554 ,00 00 H

ATOM 2331 1HG2 THR 149 17.885 37.488 28.576 ,00 00 H

ATOM 2332 2HG2 THR 149 18.429 35.914 29.195 .00 00 H

ATOM 2333 3HG2 THR 149 18.357 36.203 27.437 .00 00 H

ATOM 2334 N SER 150 14.237 33.870 29.679 .00 00 N

ATOM 2335 CA SER 150 12.789 33.692 30.034 ,00 00 C

ATOM 2336 C SER 150 11.733 34.773 29.577 ,00 00 C

ATOM 2337 0 SER 150 10.533 34.538 29.746 .00 00 O ATOM 2338 CB SER 150 12..705 33.,473 31.,565 0.00 0.,00 C

ATOM 2339 OG SER 150 11. ,415 32. ,975 31, .930 0. .00 0, ,00 0

ATOM 2340 H SER 150 14. .989 33. ,648 30, .355 0. ,00 0. ,00 H

ATOM 2341 HA SER 150 12, ,461 32. ,745 29. .561 0, .00 0, .00 H

ATOM 2342 1HB SER 150 12. ,931 34, ,408 32, .114 0. .00 0. .00 H

ATOM 2343 2HB SER 150 13. .471 32, .739 31, .896 0. ,00 0, .00 H

ATOM 2344 HG SER 150 10, .773 33, .489 31, .421 0, .00 0, ,00 H

ATOM 2345 N GLY 151 12. .147 35, .912 28 .996 1, .00 0, .00 N

ATOM 2346 CA GLY 151 11. .236 36. .800 28. .218 1. ,00 0, .00 C

ATOM 2347 C GLY 151 11. .759 37. .237 26, .830 1. ,00 0, .00 C

ATOM 2348 O GLY 151 11. .831 38. .434 26 .547 1, ,00 0, .00 O

ATOM 2349 H GLY 151 13. .166 35. .914 28 .861 1, ,00 0, .00 H

ATOM 2350 lHA GLY 151 10. .237 36. .348 28, .065 1. .00 0, .00 H

ATOM 2351 2HA GLY 151 11, .040 37, ,713 28, .810 1. .00 0, .00 H

ATOM 2352 N GLY 152 12, .084 36, ,281 25 .943 0, .00 0, .00 N

ATOM 2353 CA GLY 152 12, .293 36, .564 24 .488 0, .00 0, .00 C

ATOM 2354 C GLY 152 13. .631 37. ,126 23, .940 0, .00 0, .00 C

ATOM 2355 O GLY 152 13. .847 37. ,048 22, .731 0. .00 0, .00 O

ATOM 2356 H GLY 152 12, .113 35, .335 26 .347 0. ,00 0, .00 H

ATOM 2357 1HA GLY 152 11, .501 37, .245 24 .120 0, .00 0 .00 H

ATOM 2358 2HA GLY 152 12, ,107 35. ,627 23, .932 0, ,00 0, .00 H

ATOM 2359 N THR 153 14, .517 37, ,692 24 .770 1. ,00 0, .00 N

ATOM 2360 CA THR 153 15, .790 38, .318 2 .290 1, .00 0 .00 C

ATOM 2361 C THR 153 16, .874 37, .228 23 .981 1, .00 0 .00 C

ATOM 2362 O THR 153 17, .197 36, .399 24, .843 1. ,00 0 .00 O

ATOM 2363 CB THR 153 16, .273 39, .392 25 .315 1, ,00 0 .00 C

ATOM 2364 OG1 THR 153 15, .229 40, .331 25 .560 1, .00 0 .00 O

ATOM 2365 CG2 THR 153 17 .504 40, .211 24 .869 1, .00 0 .00 C

ATOM 2366 H THR 153 14, .227 37, .646 25 .754 1, .00 0, .00 H

ATOM 2367 HA THR 153 15, .563 38, .874 23 .355 1, .00 0 .00 H

ATOM 2368 HB THR 153 16. .523 38, .888 26 .271 1, .00 0 .00 H

ATOM 2369 HG1 THR 153 14 .425 39, .824 25 .717 1, .00 0 .00 H

ATOM 2370 1HG2 THR 153 17, .819 40, .913 25 .662 1. .00 0, .00 H

ATOM 2371 2HG2 THR 153 18, .377 39, .572 24 .635 1, .00 0 .00 H

ATOM 2372 3HG2 THR 153 1 .284 40, .816 23 .971 1, .00 0 .00 H

ATOM 2373 N VAL 154 17 .416 37, .239 22 .750 1, .00 0 .00 N

ATOM 2374 CA VAL 154 18, .483 36, .283 22 .311 1, .00 0, .00 C

ATOM 2375 C VAL 154 19 .917 36, .828 22 .635 1, .00 0 .00 C

ATOM 2376 O VAL 154 20 .178 38, .032 22 .553 1, .00 0 .00 O

ATOM 2377 CB VAL 154 18 .370 35, .851 20 .795 1, .00 0 .00 C

ATOM 2378 CGI VAL 154 16, .946 35, .498 20 .311 1, ,00 0, .00 C

ATOM 2379 CG2 VAL 154 19 .041 36, .805 19 .776 1, .00 0 .00 C

ATOM 2380 H VAL 154 17 .010 37, .932 22 .115 1, .00 0 .00 H

ATOM 2381 HA VAL 154 18 .341 35 .347 22 .886 1, .00 0 .00 H

ATOM 2382 HB VAL 154 18, .939 34, .901 20 .717 1, .00 0, .00 H

ATOM 2383 1HG1 VAL 154 16 .263 36, .367 20 .353 1, .00 0 .00 H

ATOM 2384 2HG1 VAL 154 16 .925 35, .129 19 .270 1, ,00 0 .00 H

ATOM 2385 3HG1 VAL 154 16 .491 34 .711 20 .942 1, .00 0 .00 H

ATOM 2386 2HG2 VAL 154 20, .145 36, .731 19. .820 1, ,00 0 .00 H

ATOM 2387 3HG2 VAL 154 18 .763 36, .582 18 .732 1, ,00 0 .00 H

ATOM 2388 1HG2 VAL 154 18 .809 37, .864 19 .980 1, ,00 0 .00 H

ATOM 2389 N LYS 155 20 .871 35, .919 22 .868 0, .00 0 .00 N

ATOM 2390 CA LYS 155 22, ,313 36, .263 22 .964 0, ,00 0, .00 C

ATOM 2391 C LYS 155 23, .165 35, .203 22, .193 0, .00 0, .00 C

ATOM 2392 0 LYS 155 23, .249 34, .035 22 .588 0, .00 0 .00 O

ATOM 2393 CB LYS 155 22 .695 36, .416 24 .462 0, .00 0 .00 C

ATOM 2394 CG LYS 155 22, .345 37. ,807 25, .043 0, ,00 0, .00 C

ATOM 2395 CD LYS 155 22, .719 37, ,991 26, .527 0, .00 0, .00 C

ATOM 2396 CE LYS 155 22, .794 39, ,471 26, .940 0, .00 0, .00 C

ATOM 2397 NZ LYS 155 24, .108 40, .052 26, .589 0, .00 0, .00 N

ATOM 2398 H LYS 155 20, .510 34, .976 23, ,082 0. ,00 0. .00 H

ATOM 2399 HA LYS 155 22, ,503 37, .240 22, ,476 0. ,00 0. .00 H

ATOM 2400 1HB LYS 155 23, .778 36. ,248 24, ,578 0. ,00 0. .00 H

ATOM 2401 2HB LYS 155 22, .228 35, .608 25. ,059 0. ,00 0, .00 H

ATOM 2402 1HG LYS 155 21. .260 38. ,006 24, ,920 0. 00 0, ,00 H ATOM 2403 2HG LYS 155 22..829 38.,582 24,.416 0,,00 0..00 H

ATOM 2404 1HD LYS 155 23. .648 37. ,450 26, .792 0, .00 0, .00 H

ATOM 2405 2HD LYS 155 21. .942 37. .488 27, ,137 0 .00 0. .00 H

ATOM 2406 1HE LYS 155 22. .628 39, .553 28, .045 0 .00 0. .00 H

ATOM 2407 2HE LYS 155 21. ,949 40. .050 26, ,497 0 .00 0, ,00 H

ATOM 2408 1HZ LYS 155 24, .176 41. .046 26, ,851 1, .00 0. ,00 H

ATOM 2409 2HZ LYS 155 24, .868 39, .619 27, .124 1 .00 0. .00 H

ATOM 2410 3HZ LYS 155 24, .352 39, .996 25, .584 1 .00 0, .00 H

ATOM 2411 N LEU 156 23, .825 35. ,613 21, .094 0, .00 0. .00 N

ATOM 2412 CA LEU 156 24, .762 34, .739 20, .329 0 .00 0, .00 C

ATOM 2413 C LEU 156 26, .053 34, .380 21, .143 0 .00 0, .00 C

ATOM 2414 O LEU 156 26, .734 35, .277 21, .647 0 .00 0, .00 O

ATOM 2415 CB LEU 156 25. ,176 35. .423 18, .991 0, .00 0, .00 C

ATOM 2416 CG LEU 156 24, .091 35, .858 17, .971 0, .00 0. .00 C

ATOM 2417 CD1 LEU 156 24, .770 36, .339 16, .678 0 .00 0, .00 C

ATOM 2418 CD2 LEU 156 23, .098 34, .742 17, .615 0 .00 0, .00 C

ATOM 2419 H LEU 156 23. .566 36. .554 20. .770 0, .00 0. .00 H

ATOM 2420 HA LEU 156 24. .231 33, .797 20. .076 0 .00 0. .00 H

ATOM 2421 1HB LEU 156 25, .868 34, .730 18, .472 0 .00 0, .00 H

ATOM 2422 2HB LEU 156 25, .802 36 .306 19, .225 0 .00 0, .00 H

ATOM 2423 HG LEU 156 23, .517 36, .705 18, .400 0, .00 0, ,00 H

ATOM 2424 1HD1 LEU 156 24, .029 36, .712 15, .946 0 .00 0. .00 H

ATOM 2425 2HD1 LEU 156 25, .475 37, .172 16, .864 0 .00 0, .00 H

ATOM 2426 3HD1 LEU 156 25 .339 35 .534 16, .175 0 .00 0, .00 H

ATOM 2427 1HD2 LEU 156 22, .370 35, .061 16, .846 0, .00 0, .00 H

ATOM 2428 2HD2 LEU 156 23, .611 33, .842 17, .231 0 .00 0, .00 H

ATOM 2429 3HD2 LEU 156 22 .505 34 .427 18, .493 0 .00 0, .00 H

ATOM 2430 N ALA 157 26 .377 33 .085 21 .273 0 .00 0, .00 N

ATOM 2431 CA ALA 157 27, .514 32, .595 22, .098 0, .00 0, .00 C

ATOM 2432 C ALA 157 28, .525 31, .684 21, .319 0 .00 0, .00 C

ATOM 2433 O ALA 157 28, .287 31 .263 20, .185 0 .00 0, .00 O

ATOM 2434 CB ALA 157 26 .849 31 .894 23 .303 0 .00 0, .00 C

ATOM 2435 H ALA 157 25, .699 32, .408 20, .890 0, .00 0, .00 H

ATOM 2436 HA ALA 157 28, .109 33 .445 22, .481 0 .00 0, .00 H

ATOM 2437 1HB ALA 157 27 .592 31 .520 24 .029 0 .00 0, .00 H

ATOM 2438 2HB ALA 157 26 .175 32 .574 23 .857 0 .00 0, .00 H

ATOM 2439 3HB ALA 157 26, .244 31, .018 22, .996 0, .00 0, .00 H

ATOM 2440 N ASP 158 29, .684 31 .385 21, .942 0 .00 0, .00 N

ATOM 2441 CA ASP 158 30 .753 30 .508 21, .349 0 .00 0, .00 C

ATOM 2442 C ASP 158 31 .359 30 .999 19 .977 0 .00 0, .00 C

ATOM 2443 O ASP 158 31, .376 30 .268 18, .983 0, .00 0, ,00 O

ATOM 2444 CB ASP 158 30 .308 29, .013 21, .334 0, .00 0, .00 C

ATOM 2445 CG ASP 158 29 .948 28 .365 22, .672 0, .00 0, .00 C

ATOM 2446 OD1 ASP 158 30 .219 28 .835 23, .771 0 .00 0, .00 O

ATOM 2447 OD2 ASP 158 29, .291 27, .185 22, .511 0, .00 0, ,00 O

ATOM 2448 H ASP 158 29 .669 31 .605 22, .941 0, .00 0, ,00 H

ATOM 2449 HA ASP 158 31 .603 30 .553 22, .055 0, .00 0, .00 H

ATOM 2450 1HB ASP 158 31 .109 28 .410 20 .883 0 .00 0, .00 H

ATOM 2451 2HB ASP 158 29, .452 28, .891 20, .647 0, .00 0, ,00 H

ATOM 2452 N PHE 159 31 .873 32 .240 19, .940 0, .00 0, ,00 N

ATOM 2453 CA PHE 159 32 .229 32 .947 18, .673 0, .00 0, ,00 C

ATOM 2454 C PHE 159 33 .671 33 .556 18, .673 0, .00 0, .00 C

ATOM 2455 O PHE 159 34, .249 33, .849 19, .725 0, ,00 0. ,00 O

ATOM 2456 CB PHE 159 31 .110 33, .996 18, .377 0. .00 0. .00 C

ATOM 2457 CG PHE 159 30 .929 35 .223 19, .299 0, .00 0. .00 C

ATOM 2458 GDI PHE 159 31 .786 36 .322 19, .182 0, .00 0, .00 C

ATOM 2459 CE1 PHE 159 31, .618 37, .435 20. .002 0, ,00 0, .00 C

ATOM 2460 CZ PHE 159 30, .581 37, .472 20. .928 0. ,00 0, .00 C

ATOM 2461 CE2 PHE 159 29, .714 36 .391 21, .042 0, ,00 0, .00 C

ATOM 2462 CD2 PHE 159 29, .881 35, .271 20, .227 0, ,00 0. .00 C

ATOM 2463 H PHE 159 31, .674 32, ,770 20, .794 0, ,00 0. ,00 H

ATOM 2464 HA PHE 159 32, .198 32, .226 17, .829 0, ,00 0. ,00 H

ATOM 2465 1HB PHE 159 30, .154 33, .445 18, .334 0, ,00 0. ,00 H

ATOM 2466 2HB PHE 159 31, .229 34, .360 17. .340 0, ,00 0. ,00 H

ATOM 2467 HD1 PHE 159 32. ,588 36, .318 18. ,458 0. 00 0. 00 H ATOM 2468 HE1 PHE 159 32.,278 38..281 19.,906 0.,00 0.,00 H

ATOM 2469 HZ PHE 159 30. ,444 38, .339 21. ,559 0. ,00 0, ,00 H

ATOM 2470 HE2 PHE 159 28. ,914 36, .430 21. .764 0. ,00 0. .00 H

ATOM 2471 HD2 PHE 159 29. ,191 34, .445 20, .314 0. ,00 0. .00 H

ATOM 2472 N GLY 160 34. ,244 33. .810 17, .481 0. .00 0. .00 N

ATOM 2473 CA GLY 160 35. ,499 34. .618 17, .360 0. .00 0. .00 C

ATOM 2474 C GLY 160 36. ,880 33. .927 17, .444 0, .00 0. .00 C

ATOM 2475 O GLY 160 37. ,803 34. .350 16, .746 0. .00 0. .00 O

ATOM 2476 H GLY 160 33. ,681 33. .521 16. .671 0. .00 0. .00 H

ATOM 2477 1HA GLY 160 35. ,502 35, .449 18. ,092 0, .00 0. .00 H

ATOM 2478 2HA GLY 160 35. ,469 35, .139 16. ,385 0. ,00 0. ,00 H

ATOM 2479 N LEU 161 37. .046 32. .916 18. ,308 0, ,00 0, ,00 N

ATOM 2480 CA LEU 161 38, .340 32, .201 18. ,501 0. .00 0, ,00 C

ATOM 2481 C LEU 161 38, .919 31, .509 17. ,217 0, .00 0, ,00 C

ATOM 2482 O LEU 161 38, .189 30, .927 16, .407 0, .00 0, ,00 O

ATOM 2483 CB LEU 161 38, .179 31, .146 19, ,639 0. .00 0, .00 C

ATOM 2484 CG LEU 161 37. .800 31, .623 21, .068 0, .00 0, ,00 C

ATOM 2485 CD1 LEU 161 37. .745 30, .420 22, .023 0, .00 0, .00 C

ATOM 2486 CD2 LEU 161 38. .786 32, .651 21, .639 0, .00 0, ,00 C

ATOM 2487 H LEU 161 36. ,199 32, .736 18, .860 0. .00 0, .00 H

ATOM 2488 HA LEU 161 39. ,074 32, .962 18, .836 0. .00 0, .00 H

ATOM 2489 1HB LEU 161 39. .124 30, .574 19, .715 0. .00 0, .00 H

ATOM 2490 2HB LEU 161 37. .427 30, .400 19, .310 0. .00 0, .00 H

ATOM 2491 HG LEU 161 36, .792 32, .089 21, .033 0, .00 0, .00 H

ATOM 2492 1HD1 LEU 161 37, .396 30, .721 23, .029 0, .00 0, .00 H

ATOM 2493 2HD1 LEU 161 37, .034 29 .656 21, .664 0, .00 0, .00 H

ATOM 2494 3HD1 LEU 161 38, .728 29, .930 22, .147 0, .00 0, .00 I-I

ATOM 2495 1HD LEU 161 38, .526 32. .934 22, .676 0, .00 0. .00 H

ATOM 2496 2HD2 LEU 161 39, .830 32 .289 21, .644 0, .00 0, .00 H

ATOM 2497 3HD2 LEU 161 38, .768 33 .593 21, .058 0, .00 0 .00 H

ATOM 2498 N ALA 162 40, .253 31 .561 17 .052 0, .00 0 .00 N

ATOM 2499 CA ALA 162 40, .941 30 .944 15 .891 0, .00 0 .00 C

ATOM 2500 C ALA 162 40, .862 29 .378 15 .862 0, .00 0 .00 C

ATOM 2501 O ALA 162 41, .052 28 .707 16 .882 0, .00 0 .00 O

ATOM 2502 CB ALA 162 4 .393 31 .458 15 .946 0 .00 0 .00 C

ATOM 2503 H ALA 162 40 .732 32 .179 17 .714 0 .00 0 .00 H

ATOM 2504 HA ALA 162 40 .478 31 .355 14 .971 0 .00 0 .00 H

ATOM 2505 1HB ALA 162 42 .988 31 .099 15 .087 0 .00 0 .00 H

ATOM 2506 2HB ALA 162 42 .442 32 .566 15 .916 0 .00 0 .00 H

ATOM 2507 3HB ALA 162 42 .922 31 .135 16 .862 0 .00 0 .00 H

ATOM 2508 N ARG 163 40 .563 28 .795 14 .684 1. .00 0 .00 N

ATOM 2509 CA ARG 163 40 .377 27 .319 14 .537 1, .00 0 .00 C

ATOM 2510 C ARG 163 41 .740 26 .535 14 .542 1, .00 0 .00 C

ATOM 2511 O ARG 163 42 .390 26 .338 13 .512 1 .00 0 .00 O

ATOM 2512 CB ARG 163 39 .488 27 .075 13 .285 1 .00 0 .00 C

ATOM 2513 CG ARG 163 39 .007 25 .612 13 .117 1. .00 0 .00 C

ATOM 2514 CD ARG 163 38 .151 25 .409 11 .857 1 .00 0 .00 C

ATOM 2515 NE ARG 163 37 .740 23 .982 11 .797 1, .00 0 .00 N

ATOM 2516 CZ ARG 163 37 .248 23 .362 10 .732 1, .00 0 .00 C

ATOM 2517 NH1 ARG 163 37 .044 23 .927 9 .579 1, .00 0 .00 N

ATOM 2518 NH2 ARG 163 36 .953 22 .116 10 .858 1, .00 0 .00 N

ATOM 2519 H ARG 163 40 .483 29 .449 13 .905 1, .00 0 .00 H

ATOM 2520 HA ARG 163 39 .773 26 .969 15 .399 1, .00 0 .00 H

ATOM 2521 1HB ARG 163 38 .597 27 .734 13 .330 1, .00 0 .00 H

ATOM 2522 2HB ARG 163 40 .046 27 .390 12 .379 1, .00 0 .00 H

ATOM 2523 1HG ARG 163 39 .891 24 .940 13 .073 1, .00 0 .00 H

ATOM 2524 HG ARG 163 38 .435 25 .307 14 .016 1, .00 0 .00 H

ATOM 2525 1HD ARG 163 37 .260 26 .073 11 .878 1, .00 0 .00 H

ATOM 2526 2HD ARG 163 38 .741 25 .704 10 .962 1, .00 0 .00 H

ATOM 2527 HE ARG 163 37 .836 23 .366 12 .608 1, .00 0 .00 H

ATOM 2528 2HH1 ARG 163 37 .310 24 .911 9, .518 1, .00 0 .00 H

ATOM 2529 1HH1 ARG 163 36 .699 23 .351 8, .804 1, .00 0, .00 H

ATOM 2530 1HH2 ARG 163 37 .146 21 .670 11, .754 1, .00 0 .00 H

ATOM 2531 2HH2 ARG 163 36 .620 21 .641 10, .013 1. .00 0, .00 H

ATOM 2532 N ILE 164 42 .147 26 .115 15, .744 0. .00 0, .00 N ATOM 2533 CA ILE 164 43.477 25.489 16.019 00 0.00 C

ATOM 2534 C ILE 164 43.379 23.925 16.219 00 0.00 c

ATOM 2535 O ILE 164 42.316 23.312 16.072 00 00 0

ATOM 2536 CB ILE 164 44.151 26.272 17.219 00 00 c

ATOM 2537 CG2 ILE 164 44.676 27.668 16.798 00 00 C

ATOM 2538 CGI ILE 164 43.301 26.350 18.526 0.00 0.00 c

ATOM 2539 CD1 ILE 164 44.063 26.685 19.818 0.00 0.00 c

ATOM 2540 H ILE 164 41.682 26.640 16.493 00 00 H

ATOM 2541 HA ILE 164 44.140 25.611 15.137 00 00 H

ATOM 2542 HB ILE 164 45.056 25.704 17.478 0.00 00 H

ATOM 2543 1HG2 ILE 164 45.297 28.136 17.585 0.00 00 H

ATOM 2544 2HG2 ILE 164 45.317 27.614 15.897 00 00 H

ATOM 2545 3HG2 ILE 164 43.854 28.373 16.569 00 00 H

ATOM 2546 1HG1 ILE 164 42.807 25.376 18.689 00 00 H

ATOM 2547 2HG1 ILE 164 42.478 27.079 18.398 00 00 H

ATOM 2548 1HD1 ILE 164 43.378 26.744 20.684 00 00 H

ATOM 2549 2HD1 ILE 164 44.816 25.916 20.068 00 00 H

ATOM 2550 3HD1 ILE 164 44.576 27.663 19.770 00 00 H

ATOM 2551 N TYR 165 44.504 23.256 16.537 00 00 N

ATOM 2552 CA TYR 165 44.514 21.814 16.920 00 00 c

ATOM 2553 C TYR 165 44.587 21.628 18.478 00 00 c

ATOM 2554 0 TYR 165 45.634 21.852 19.092 00 00 o

ATOM 2555 CB TYR 165 45.689 21.129 16.158 00 00 c

ATOM 2556 CG TYR 165 45.786 19.603 16.361 00 00 c

ATOM 2557 CD1 TYR 165 44.979 18.738 15.612 0.00 00 c

ATOM 2558 CE1 TYR 165 45.029 17.363 15.837 0.00 00 c

ATOM 2559 CZ TYR 165 45.881 16.845 16.806 00 00 c

ATOM 2560 OH TYR 165 45.942 15.496 17.016 00 00 0

ATOM 2561 CE2 TYR 165 46.692 17.696 17.553 00 00 c

ATOM 2562 CD2 TYR 165 46.647 19.071 17.327 00 00 c

ATOM 2563 H TYR 165 45.353 23.831 16.577 00 00 H

ATOM 2564 HA TYR 165 43.599 21.317 16.533 00 00 H

ATOM 2565 1HB TYR 165 46.649 21.601 16.446 00 00 H

ATOM 2566 2HB TYR 165 45.605 21.336 15.073 00 00 H

ATOM 2567 HD1 TYR 165 44.308 19.127 14.859 00 00 H

ATOM 2568 HE1 TYR 165 44.404 16.702 15.254 0.00 0.00 H

ATOM 2569 HH TYR 165 45.449 15.048 16.325 0.00 0.00 H

ATOM 2570 HE2 TYR 165 47.351 17.286 18.305 00 00 H

ATOM 2571 HD2 TYR 165 47.272 19.723 17.923 00 00 H

ATOM 2572 N SER 166 43.524 21.019 19.013 00 00 N

ATOM 2573 CA SER 166 43.446 20.562 20.430 00 00 c

ATOM 2574 C SER 166 42.816 19.110 20.491 00 00 c

ATOM 2575 0 SER 166 41.917 18.843 21.295 00 00 0

ATOM 2576 CB SER 166 42.697 21.626 21.258 00 00 c

ATOM 2577 OG SER 166 42.612 21.236 22.628 00 00 0

ATOM 2578 H SER 166 42.811 20.755 18.327 0.00 00 H

ATOM 2579 HA SER 166 44.463 20.461 20.863 0.00 00 H

ATOM 2580 1HB SER 166 43.217 22.603 21.189 00 00 H

ATOM 2581 2HB SER 166 41.680 21.758 20.851 00 0.00 H

ATOM 2582 HG SER 166 42.269 20.330 22.648 00 0.00 H

ATOM 2583 N TYR 167 43.312 18.158 19.647 00 00 N

ATOM 2584 CA TYR 167 42.668 16.824 19.354 00 00 c

ATOM 2585 C TYR 167 41.176 17.062 18.910 00 00 c

ATOM 2586 0 TYR 167 40.952 17.622 17.833 00 00 0

ATOM 2587 CB TYR 167 42.969 15.807 20.508 00 00 c

ATOM 2588 CG TYR 167 44.456 15.511 20.781 00 00 c

ATOM 2589 GDI TYR 167 45.149 14.579 20.003 00 00 c

ATOM 2590 CE1 TYR 167 46.509 14.357 20.218 00 00 c

ATOM 2591 CZ TYR 167 47.180 15.059 21.214 00 00 c

ATOM 2592 OH TYR 167 48.516 14.853 21.421 00 00 0

ATOM 2593 CE2 TYR 167 46.496 15.982 22.000 00 0.00 c

ATOM 2594 CD2 TYR 167 45.138 16.207 21.787 00 0.00 c

ATOM 2595 H TYR 167 44.171 18.444 19.163 00 0.00 H

ATOM 2596 HA TYR 167 43.160 16.421 18.448 00 0.00 H

ATOM 2597 1HB TYR 167 42.484 16.156 21.440 00 0.00 H ATOM 2598 2HB TYR 167 42.,457 14,.852 20.,285 0.00 0,,00 H

ATOM 2599 HD1 TYR 167 44. ,643 14. .038 19. 217 0. 00 0. ,00 H

ATOM 2600 HE1 TYR 167 47. ,038 13. .645 19. ,601 0. 00 0, .00 H

ATOM 2601 HH TYR 167 48. ,823 14, .188 20. ,802 0. ,00 0. .00 H

ATOM 2602 HE2 TYR 167 47. ,024 16. ,522 22. ,772 0. 00 0. .00 H

ATOM 2603 HD2 TYR 167 44. ,620 16, ,934 22. ,395 0. 00 0, .00 H

ATOM 2604 N GLN 168 40, ,182 16, ,593 19. ,680 0. ,00 0. .00 N

ATOM 2605 CA GLN 168 38, ,759 16, ,985 19. .444 0. ,00 0. .00 C

ATOM 2606 c GLN 168 38. ,204 17. ,528 20. .804 0. .00 0. .00 C

ATOM 2607 O GLN 168 38, ,260 16, .830 21. ,826 0. ,00 0. .00 O

ATOM 2608 CB GLN 168 37, ,879 15, ,800 18. .940 0. ,00 0, ,00 C

ATOM 2609 CG GLN 168 38, ,176 15, ,263 17, .514 0, ,00 0, .00 C

ATOM 2610 CD GLN 168 37. ,131 14, ,285 16. .975 0. ,00 0. .00 C

ATOM 2611 OE1 GLN 168 36, ,486 13. ,531 17, ,694 0, ,00 0. .00 O

ATOM 2612 NE2 GLN 168 36. .922 14. .257 15, .684 0, ,00 0, .00 N

ATOM 2613 H GLN 168 40. ,490 16. .222 20. ,586 0, .00 0, .00 H

ATOM 2614 HA GLN 168 38. .683 17. .797 18. .692 0, .00 0, .00 H

ATOM 2615 1HB GLN 168 37. .930 14. .960 19. .664 0, .00 0. .00 H

ATOM 2616 2HB GLN 168 36. ,817 16. .120 18. .970 0. ,00 0, .00 H

ATOM 2617 1HG GLN 168 38. .287 16, .118 16. ,822 0, .00 0, .00 H

ATOM 2618 2HG GLN 168 39. .156 14, .751 17. .508 0. .00 0. .00 H

ATOM 2619 1HE2 GLN 168 37. .418 14, .939 15, .109 0, ,00 0, .00 H

ATOM 2620 2HE2 GLN 168 36, .192 13. .593 15. .408 0, .00 0, .00 H

ATOM 2621 N MET 169 37, .674 18, .764 20. .843 0, .00 0 .00 N

ATOM 2622 CA MET 169 37, ,273 19, .426 22. .125 0. .00 0, .00 C

ATOM 2623 C MET 169 36, .032 18, .775 22, ,827 0, .00 0, .00 C

ATOM 2624 Q MET 169 34, .885 19, .045 22, .464 0, .00 0 .00 O

ATOM 2625 CB MET 169 37, .060 20 .942 21, .867 0, .00 0 .00 C

ATOM 2626 CG MET 169 38, .345 21, .767 21, ,641 0, ,00 0, .00 C

ATOM 2627 SD MET 169 39, .653 21, .355 22, .823 0. .00 0, .00 S

ATOM 2628 CE MET 169 38, .933 21, .848 24, .398 0, .00 0, .00 C

ATOM 2629 H MET 169 37 .619 19 .248 19, .944 0, .00 0 .00 H

ATOM 2630 HA MET 169 38, .120 19, .340 22, .834 0, .00 0, .00 H

ATOM 2631 1HB MET 169 36, .337 21, .101 21, .042 0, .00 0 .00 H

ATOM 2632 2HB MET 169 36 .541 21 .377 22 .745 0, .00 0 .00 H

ATOM 2633 1HG MET 169 38 .734 21 .580 20 .623 0 .00 0 .00 H

ATOM 2634 2HG MET 169 38 .120 22 .848 21, .695 0, .00 0 .00 H

ATOM 2635 1HE MET 169 38 .574 22 .890 24 .363 0 .00 0 .00 H

ATOM 2636 2HE MET 169 39 .678 21 .766 25 .210 0 .00 0 .00 H

ATOM 2637 3HE MET 169 38 .077 21 .201 24 .663 0 .00 0 .00 H

ATOM 2638 N ALA 170 36 .326 17 .853 23 .796 0, .00 0 .00 N

ATOM 2639 CA ALA 170 35 .356 16 .869 24 .407 0 .00 0 .00 C

ATOM 2640 C ALA 170 34 .326 16 .212 23 .418 0 .00 0 .00 C

ATOM 2641 O ALA 170 33 .168 15 .977 23 .780 0 .00 0 .00 O

ATOM 2642 CB ALA 170 34 .684 17 .646 25, .566 0, .00 0 .00 C

ATOM 2643 H ALA 170 37 .334 17 .686 23 .876 0 .00 0 .00 H

ATOM 2644 HA ALA 170 35 .931 16 .033 24 .848 0 .00 0 .00 H

ATOM 2645 1HB ALA 170 34 .015 16 .989 26 .152 0 .00 0 .00 H

ATOM 2646 2HB ALA 170 35 .413 18 .068 26, .282 0, .00 0 .00 H

ATOM 2647 3HB ALA 170 34 .056 18 .482 25 .198 0 .00 0 .00 H

ATOM 2648 N LEU 171 34 .804 15 .784 22 .228 0 .00 0 .00 N

ATOM 2649 CA LEU 171 33 .933 15 .401 21 .066 0 .00 0 .00 C

ATOM 2650 C LEU 171 32 .899 16 .500 20, .616 0, .00 0, .00 C

ATOM 2651 O LEU 171 33 .009 17 .035 19, .510 0, .00 0 .00 O

ATOM 2652 CB LEU 171 33 .388 13 .952 21 .229 0 .00 0 .00 C

ATOM 2653 CG LEU 171 32 .538 13 .341 20 .079 0 .00 0 .00 C

ATOM 2654 GDI LEU 171 33 .307 13 .198 18, .758 0, .00 0, .00 C

ATOM 2655 CD2 LEU 171 32 .000 11 .955 20. .484 0, .00 0, .00 C

ATOM 2656 H LEU 171 35 .787 16 .045 22. .100 0, .00 0, .00 H

ATOM 2657 HA LEU 171 34 .626 15 .339 20 .206 0 .00 0 .00 H

ATOM 2658 1HB LEU 171 34 .238 13, .274 21, .439 0, .00 0, ,00 H

ATOM 2659 2HB LEU 171 32 .782 13 .923 22, .156 0, .00 0, .00 H

ATOM 2660 HG LEU 171 31 .663 14 .001 19, .901 0, .00 0, .00 H

ATOM 2661 1HD1 LEU 171 32 .690 12 .732 17, .967 0, .00 0, .00 H

ATOM 2662 2HD1 LEU 171 33 .630 14, .179 18, .363 0, .00 0, .00 H ATOM 2663 3HD1 LEU 171 34.,218 12..579 18,.870 0.,00 0.,00 H

ATOM 2664 1HD2 LEU 171 31. ,329 11. .533 19. .713 0. ,00 0. ,00 H

ATOM 2665 2HD2 LEU 171 32, ,812 11. .222 20, ,648 0. .00 0, ,00 H

ATOM 2666 3HD2 LEU 171 31, .411 12, .003 21, ,420 0, .00 0. .00 H

ATOM 2667 N THR 172 31, .910 16, .821 21. .476 0, .00 0, .00 N

ATOM 2668 CA THR 172 30, .844 17, .838 21, ,223 0. .00 0, ,00 C

ATOM 2669 C THR 172 29, .820 17, .381 20, .115 0, .00 0, .00 C

ATOM 2670 O THR 172 30, .044 17, .723 18, .949 0, .00 0, .00 O

ATOM 2671 CB THR 172 31, .395 19, .299 21, .099 0, .00 0. .00 C

ATOM 2672 OG1 THR 172 32, .228 19, .632 22, .205 0, .00 0, .00 O

ATOM 2673 CG2 THR 172 30, .294 20, .371 21, .108 0. .00 0. .00 C

ATOM 2674 H THR 172 32, .068 16, .413 22, .410 0, ,00 0, .00 H

ATOM 2675 HA THR 172 30, .286 17, .888 22, .173 0. .00 0, .00 H

ATOM 2676 HB THR 172 31, .981 19, .391 20, .163 0. .00 0, .00 H

ATOM 2677 HG1 THR 172 33, .086 19, .204 22, .082 0. .00 0, .00 H

ATOM 2678 1HG2 THR 172 30, .725 21, .385 21, .068 0, .00 0, .00 H

ATOM 2679 2HG2 THR 172 29, .594 20, .272 20, .262 0. .00 0. ,00 H

ATOM 2680 3HG2 THR 172 29, .695 20, .333 22, .040 0, .00 0, .00 H

ATOM 2681 N PRO 173 28, .697 16, .633 20, .411 0. .00 0, .00 N

ATOM 2682 CA PRO 173 27, .743 16, .140 19, .363 0. .00 0. .00 C

ATOM 2683 CD PRO 173 28, .320 16, .193 21, .770 0. .00 0, .00 C

ATOM 2684 C PRO 173 27, .157 17, .200 18, .375 0. .00 0, .00 C

ATOM 2685 O PRO 173 26, .823 16, .856 17, .246 0. .00 0, .00 O

ATOM 2686 CB PRO 173 26, .750 15, .271 20, .153 0, .00 0. .00 C

ATOM 2687 CG PRO 173 26, .871 15, .729 21, .607 0. .00 0, .00 C

ATOM 2688 HA PRO 173 28, .313 15, .454 18, .706 0. .00 0, .00 H

ATOM 2689 1HD PRO 173 28 .371 16 .998 22 .529 0, .00 0, .00 H

ATOM 2690 2HD PRO 173 28 .976 15 .366 22 .109 0, .00 0, .00 H

ATOM 2691 1HB PRO 173 25 .711 15 .347 19 .778 0, .00 0, .00 H

ATOM 2692 2HB PRO 173 27 .033 14 .204 20 .072 0, .00 0, .00 H

ATOM 2693 1HG PRO 173 26 .185 16, .581 21 .793 0, .00 0, .00 H

ATOM 2694 2HG PRO 173 26 .594 14. .942 22 .333 0, .00 0, .00 H

ATOM 2695 N VAL 174 26 .974 18 .452 18 .809 0, .00 0, .00 N

ATOM 2696 CA VAL 174 26 .605 19. .578 17 .890 0, .00 0, .00 C

ATOM 2697 C VAL 174 27 .744 20 .096 16 .929 0, .00 0, .00 C

ATOM 2698 O VAL 174 27 .415 20 .433 15, .794 0, .00 0, .00 O

ATOM 2699 CB VAL 174 25 .907 20 .760 18 .656 0, .00 0, .00 C

ATOM 2700 CGI VAL 174 24 .536 20 .370 19 .254 0, .00 0, .00 C

ATOM 2701 CG2 VAL 174 26 .754 21 .444 19 .757 0, .00 0, .00 c

ATOM 2702 H VAL 174 27 .258 18 .598 19 .783 0, .00 0, .00 H

ATOM 2703 HA VAL 174 25 .827 19 .195 17 .199 0, .00 0, .00 H

ATOM 2704 HB VAL 174 25 .685 21 .546 17 .906 0, .00 0, .00 H

ATOM 2705 1HG1 VAL 174 24 .629 19 .626 20 .068 0, .00 0, .00 H

ATOM 2706 2HG1 VAL 174 24 .016 21 .242 19 .696 0, .00 0, .00 H

ATOM 2707 3HG1 VAL 174 23 .850 19. .946 18, .499 0, .00 0, .00 H

ATOM 2708 1HG2 VAL 174 26 .982 20, .765 20, .600 0, .00 0, .00 H

ATOM 2709 2HG2 VAL 174 27 .714 21, .833 19, .372 0, .00 0, .00 H

ATOM 2710 3HG2 VAL 174 26 .226 22, .313 20, .198 0, .00 0, .00 H

ATOM 2711 N VAL 175 29, .039 20, .183 17, .321 0, .00 0, .00 N

ATOM 2712 CA VAL 175 30, .145 20, .671 16, .410 0, .00 0. .00 C

ATOM 2713 C VAL 175 30 .486 19 .648 15 .275 0 .00 0, .00 C

ATOM 2714 O VAL 175 30 .514 20 .030 14 .104 0, .00 0, .00 O

ATOM 2715 CB VAL 175 31 .395 21 .188 17 .205 0, .00 0, .00 C

ATOM 2716 CGI VAL 175 32 .559 21 .672 16 .302 0, .00 0, .00 C

ATOM 2717 CG2 VAL 175 31 .051 22. .390 18 .105 0, .00 0, .00 C

ATOM 2718 H VAL 175 29 .214 19, .785 18, .253 0, .00 0, .00 H

ATOM 2719 HA VAL 175 29, .760 21, .567 15, .888 0, .00 0, .00 H

ATOM 2720 HB VAL 175 31, .769 20, .365 17, .848 0, .00 0, .00 H

ATOM 2721 1HG1 VAL 175 32, .250 22, .515 15, .654 0, .00 0, ,00 H

ATOM 2722 2HG1 VAL 175 33, .417 22, .029 16, .904 0. .00 0. ,00 H

ATOM 2723 3HG1 VAL 175 32, .947 20, .866 15, .654 0, .00 0. ,00 H

ATOM 2724 1HG2 VAL 175 30, .579 23, .213 17, .537 0, .00 0, ,00 H

ATOM 2725 2HG2 VAL 175 30, ,338 22. ,134 18. ,907 0. .00 0, ,00 H

ATOM 2726 3HG2 VAL 175 31. ,945 22. .820 18. ,588 0, .00 0, ,00 H

ATOM 2727 N VAL 176 30. .806 18. .381 15. ,602 0. .00 0. ,00 N ATOM 2728 CA VAL 176 31.006 17.290 14.562 0.00 0.00 c

ATOM 2729 C VAL 176 29. 807 17. 134 13. 518 0. 00 0. 00 c

ATOM 2730 O VAL 176 29. 976 16. 812 12. 339 0. .00 0. ,00 0

ATOM 2731 CB VAL 176 32. 460 17. .309 13. .940 0. .00 0. ,00 c

ATOM 2732 CGI VAL 176 33. 624 17. .498 14. .947 0. ,00 0. ,00 c

ATOM 2733 CG2 VAL 176 32. 826 16. .011 13. ,180 0. ,00 0. ,00 c

ATOM 2734 H VAL 176 30. 735 18. ,182 16. ,611 0. ,00 0. ,00 H

ATOM 2735 HA VAL 176 30. 954 16. ,345 15. .136 0. ,00 0. ,00 H

ATOM 2736 HB VAL 176 32. ,493 18. .150 13. ,220 0. .00 0. ,00 H

ATOM 2737 1HG1 VAL 176 34. 616 17. ,506 14. ,459 0. ,00 0. 00 H

ATOM 2738 2HG1 VAL 176 33. 537 18. ,453 15. ,496 0. ,00 0. ,00 H

ATOM 2739 3HG1 VAL 176 33. 639 16. ,699 15. ,714 0. ,00 0. ,00 H

ATOM 2740 1HG2 VAL 176 33. ,840 16. ,047 12, ,738 0. ,00 0. ,00 H

ATOM 2741 2HG2 VAL 176 32. ,788 15. .118 13, ,833 0. ,00 0. ,00 H

ATOM 2742 3HG2 VAL 176 32. ,149 15. .805 12, ,331 0. ,00 0. ,00 H

ATOM 2743 N THR 177 28. ,567 17, .377 13. .973 0, .00 0, .00 N

ATOM 2744 CA THR 177 27. ,341 17, .437 13. .126 0, .00 0, .00 C

ATOM 2745 C THR 177 27, ,373 18, .593 12. ,053 0, .00 0, .00 c

ATOM 2746 O THR 177 27. .224 19, .770 12, .383 0, .00 0, ,00 0

ATOM 2747 CB THR 177 26. .161 17, .524 14, .151 0, .00 0, .00 c

ATOM 2748 OG1 THR 177 26. ,051 16. .301 14. .883 0, ,00 0. .00 0

ATOM 2749 CG2 THR 177 24. .780 17. .761 13. .542 0. .00 0, .00 c

ATOM 2750 H THR 177 28, ,539 17. ,624 14. .968 0. .00 0, .00 H

ATOM 2751 HA THR 177 27. .230 16. .468 12, .598 0, ,00 0, .00 H

ATOM 2752 HB THR 177 26. ,343 18. .355 14, .861 0, .00 0, .00 H

ATOM 2753 HG1 THR 177 26. .133 16, .523 15, .826 0, .00 0, .00 H

ATOM 754 1HG2 THR 177 23, ,989 17, .738 14, .314 0, .00 0, .00 H

ATOM 2755 2HG2 THR 177 24, .700 18, .737 13, .030 0, .00 0, .00 H

ATOM 2756 3HG2 THR 177 24, .536 16, .974 12, .806 0, .00 0, .00 H

ATOM 2757 N LEU 178 27, .528 18, .239 10 .766 0, .00 0, .00 N

ATOM 2758 CA LEU 178 27, .644 19 .225 9 .642 0, .00 0 .00 C

ATOM 2759 C LEU 178 26, .333 19 .957 9 .135 0, .00 0, .00 C

ATOM 2760 O LEU 178 26, .400 20, .676 8, .133 0, .00 0, .00 0

ATOM 2761 CB LEU 178 28, .310 18, .459 8, .451 0, .00 0, .00 C

ATOM 2762 CG LEU 178 29, .771 17, .952 8, .600 0, .00 0, .00 C

ATOM 2763 CD1 LEU 178 30, .125 17, .047 7 .409 0, .00 0, .00 C

ATOM 2764 CD2 LEU 178 30 .793 19 .100 8 .660 0, .00 0, .00 C

ATOM 2765 H LEU 178 27, .742 17 .244 10 .623 0, .00 0, .00 H

ATOM 2766 HA LEU 178 28 .325 20 .040 9 .945 0, .00 0. .00 H

ATOM 2767 1HB LEU 178 28 .277 19 .089 7 .540 0, .00 0 .00 H

ATOM 2768 2HB LEU 178 27 .654 17 .603 8 .185 0 .00 0 .00 H

ATOM 2769 HG LEU 178 29 .856 17 .341 9 .522 0 .00 0 .00 H

ATOM 2770 1HD1 LEU 178 31 .142 16 .622 7 .492 0 .00 0 .00 H

ATOM 2771 2HD1 LEU 178 29 .432 16 .188 7 .333 0 .00 0 .00 H

ATOM 2772 3HD1 LEU 178 30 .075 17 .580 6 .439 0, .00 0, .00 H

ATOM 2773 1HD2 LEU 178 31 .824 18 .710 8 .752 0 .00 0, .00 H

ATOM 2774 2HD2 LEU 178 30 .768 19 .723 7 .745 0 .00 0 .00 H

ATOM 2775 3HD2 LEU 178 30 .615 19 .754 9 .529 0 .00 0 .00 H

ATOM 2776 N TRP 179 25 .170 19 .839 9 .807 0 .00 0 .00 N

ATOM 2777 CA TRP 179 23 .847 20 .319 9 .279 0 .00 0 .00 C

ATOM 2778 C TRP 179 23 .701 21 .840 8 .909 0 .00 0 .00 C

ATOM 2779 O TRP 179 23 .064 22 .175 7 .907 0 .00 0 .00 0

ATOM 2780 CB TRP 179 22 .726 19 .916 10 .284 0 .00 0 .00 C

ATOM 2781 CG TRP 179 22 .512 18 .430 10 .633 0 .00 0 .00 C

ATOM 2782 GDI TRP 179 23 .013 17 .304 9 .940 0 .00 0 .00 C

ATOM 2783 NE1 TRP 179 22 .690 16 .099 10 .587 0 .00 0 .00 N

ATOM 2784 CE2 TRP 179 21 .999 16 .500 11 .716 0, .00 0 .00 C

ATOM 2785 CD2 TRP 179 21 .875 17 .915 11, .752 0, .00 0 .00 C

ATOM 2786 CE3 TRP 179 21 .321 18 .556 12, .893 0, .00 0 .00 C

ATOM 2787 CZ3 TRP 179 20 .920 17 .765 13 .972 0, .00 0 .00 C

ATOM 2788 CH2 TRP 179 21 .055 16 .372 13 .939 0, .00 0, .00 C

ATOM 2789 CZ2 TRP 179 21 .597 15 .724 12 .826 0, .00 0, .00 C

ATOM 2790 H TRP 179 25 .225 19 .152 10, .567 0. .00 0, .00 H

ATOM 2791 HA TRP 179 23 .646 19 .773 8, .336 0. ,00 0, .00 H

ATOM 2792 1HB TRP 179 21 .757 20 .280 9, .891 0, ,00 0, .00 H ATOM 2793 2HB TRP 179 22,.866 20..485 11,,224 0..00 0.00 H

ATOM 2794 HD1 TRP 179 23. .616 17. .365 9. .044 0. .00 0. ,00 H

ATOM 2795 HE1 TRP 179 23. .030 15. ,159 10. ,348 0, .00 0. ,00 H

ATOM 2796 HE3 TRP 179 21 .248 19, .634 12, .946 0, .00 0. .00 H

ATOM 2797 HZ3 TRP 179 20 .530 18, .247 14, .856 0, .00 0. .00 H

ATOM 2798 HH2 TRP 179 20 .765 15, .787 14, .801 0, .00 0, .00 H

ATOM 2799 HZ2 TRP 179 21 .742 14, .654 12, .825 0, .00 0. .00 H

ATOM 2800 N TYR 180 24 .274 22, .749 9, .713 0, .00 0. .00 N

ATOM 2801 CA TYR 180 24 .162 24, .233 9, .505 0, .00 0, .00 C

ATOM 2802 C TYR 180 25 .333 24, .889 8, .663 0, .00 0, .00 C

ATOM 2803 O TYR 180 25 .528 26, .108 8, .711 0, .00 0, .00 O

ATOM 2804 CB TYR 180 24 .007 24, .900 10, .915 0, .00 0, .00 C

ATOM 2805 CG TYR 180 22 .881 24, .364 11, .825 0, .00 0, .00 C

ATOM 2806 CD1 TYR 180 21 .558 24, .785 11, .656 0, .00 0. .00 C

ATOM 2807 CE1 TYR 180 20 .531 24, .175 12, .370 0, .00 0, .00 C

ATOM 2808 CZ TYR 180 20 .821 23, .147 13, .267 0, .00 0. ,00 C

ATOM 2809 OH TYR 180 19 .819 22, .521 13, .945 0, .00 0. ,00 O

ATOM 2810 CE2 TYR 180 22 .137 22, .744 13, .465 0, .00 0. .00 C

ATOM 2811 CD2 TYR 180 23 .161 23, .346 12, .746 0, .00 0. .00 C

ATOM 2812 H TYR 180 24 .721 22, .326 10, .529 1, .00 0, .00 H

ATOM 2813 HA TYR 180 23 .235 24, .464 8, .941 0, .00 0, .00 H

ATOM 2814 1HB TYR 180 23 .841 25 .988 10, .778 0, .00 0, .00 H

ATOM 2815 2HB TYR 180 24 .972 24 .865 11, .451 0, .00 0. .00 H

ATOM 2816 HD1 TYR 180 21 .317 25, .573 10, .956 0, .00 0, .00 H

ATOM 2817 HE1 TYR 180 19 .507 24, .496 12, .228 0, .00 0. .00 H

ATOM 2818 HH TYR 180 18 .939 22 .873 13, .676 0, .00 0. .00 H

ATOM 2819 HE2 TYR 180 22 .349 21 .949 14 .165 0 .00 0, .00 H

ATOM 2820 HD2 TYR 180 24 .168 22 .986 12 .880 0 .00 0, .00 H

ATOM 2821 N ARG 181 26 .106 24 .099 .893 0 .00 0, .00 N

ATOM 2822 CA ARG 181 27 .344 24 .543 7 .193 0. .00 0, .00 C

ATOM 2823 C ARG 181 27 .080 25 .118 5. .764 0 .00 0, .00 C

ATOM 2824 O ARG 181 26 .320 24 .550 4 .973 0 .00 0, .00 0

ATOM 2825 CB ARG 181 28 .278 23 .302 7. .065 0 .00 0, .00 c

ATOM 2826 CG ARG 181 28 .949 22 .768 8. .352 0 .00 0, .00 c

ATOM 2827 CD ARG 181 30 .192 23 .558 8. .790 0 .00 0, .00 c

ATOM 2828 NE ARG 181 30 .803 22 .864 9 .953 0 .00 0, .00 N

ATOM 2829 CZ ARG 181 30 .823 23 .294 11 .207 0 .00 0, .00 C

ATOM 2830 NH1 ARG 181 30 .330 24 .424 11 .617 0 .00 0, .00 N

ATOM 2831 NH2 ARG 181 31 .352 22 .516 12 .083 0 .00 0, .00 N

ATOM 2832 H ARG 181 25 .777 23 .126 7, .860 0 .00 0, .00 H

ATOM 2833 HA ARG 181 27 .854 25 .317 7, .802 0. .00 0, ,00 H

ATOM 2834 1HB ARG 181 29 .072 23 .507 6 .318 0, .00 0, .00 H

ATOM 2835 2HB ARG 181 27 .703 22 .477 6 .594 0, .00 0. .00 H

ATOM 2836 1HG ARG 181 29 .231 21 .714 8. .150 0, .00 0. ,00 H

ATOM 2837 2HG ARG 181 28 .197 22 .706 9, .164 0, .00 0. .00 H

ATOM 2838 1HD ARG 181 29 .936 24 .622 8, .974 0, .00 0. ,00 H

ATOM 2839 2HD ARG 181 30 .920 23 .591 7, .950 0, .00 0, ,00 H

ATOM 2840 HE ARG 181 31 .235 21 .944 9 .817 1, .00 0, ,00 H

ATOM 2841 1HH1 ARG 181 30 .426 24. .683 12, .614 0, .00 0. ,00 H

ATOM 2842 2HH1 ARG 181 29 .956 25 .036 10, .886 0, .00 0, ,00 H

ATOM 2843 1HH2 ARG 181 31 .374 22 .882 13 .043 0 .00 0, .00 H

ATOM 2844 2HH2 ARG 181 31 .683 21 .600 11 .774 0 .00 0, .00 H

ATOM 2845 N ALA 182 27 .781 26 .207 5. .413 0 .00 0, .00 N

ATOM 2846 CA ALA 182 27 .734 26 .776 .045 0 .00 0, .00 C

ATOM 2847 C ALA 182 28 .556 25 .980 2 .958 0, .00 0, .00 C

ATOM 2848 O ALA 182 29 .679 25 .562 3, .270 0, .00 0, .00 O

ATOM 2849 CB ALA 182 28 .253 28 .214 4, .183 0, .00 0, ,00 C

ATOM 2850 H ALA 182 28 .342 26. .641 6, .149 0, .00 0. ,00 H

ATOM 2851 HA ALA 182 26 .675 26 .843 3, .739 0, .00 0. .00 H

ATOM 2852 1HB ALA 182 28 .156 28, .763 3, .229 0, .00 0, .00 H

ATOM 2853 2HB ALA 182 27 .714 28, .801 4, .950 0, .00 0, .00 H

ATOM 2854 3HB ALA 182 29 .327 28, .233 4, .437 0. .00 0. .00 H

ATOM 2855 N PRO 183 28 .095 25, .806 1. .678 0. .00 0, .00 N

ATOM 2856 CA PRO 183 28 .875 25, .103 0, .613 0. .00 0. ,00 C

ATOM 2857 CD PRO 183 26 .709 26, .111 1, .264 0. .00 0. ,00 C ATOM 2858 C PRO 183 30.391 25..402 0,,366 0.,00 0.,00 c

ATOM 2859 0 PRO 183 31. 143 24. .470 0, ,086 0. ,00 0. ,00 0

ATOM 2860 CB PRO 183 28. 009 25. ,354 -0. ,634 0. ,00 0. ,00 c

ATOM 2861 CG PRO 183 26. ,578 25, .457 -0, .110 0, ,00 0. ,00 c

ATOM 2862 HA PRO 183 28. ,823 24, .023 0, .847 0, .00 0, ,00 H

ATOM 2863 1HD PRO 183 26. ,554 27, .207 1, .201 0, ,00 0. ,00 H

ATOM 2864 2HD PRO 183 25, ,953 25, .702 1, .963 0. .00 0. .00 H

ATOM 2865 1HB PRO 183 28, .131 24, .554 -1, .388 0, .00 0. ,00 H

ATOM 2866 2HB PRO 183 28. .298 26, .304 -1. .130 0, .00 0, .00 H

ATOM 2867 1HG PRO 183 26, .148 24, .444 -0, .005 0, .00 0. .00 H

ATOM 2868 2HG PRO 183 25. ,911 26, .023 -0, .788 0. .00 0, .00 H

ATOM 2869 N GLU 184 30. ,853 26, .655 0, .502 0, .00 0. .00 N

ATOM 2870 CA GLU 184 32. .310 26, .998 0, ,506 0, ,00 0. ,00 C

ATOM 2871 C GLU 184 33. ,224 26, .415 1, .651 0, ,00 0. .00 C

ATOM 2872 0 GLU 184 34. ,417 26, .217 1, .423 0. .00 0, ,00 0

ATOM 2873 CB GLU 184 32, ,462 28, .536 0, .324 0, .00 0, .00 C

ATOM 2874 CG GLU 184 32, .003 29, .483 1, .473 0, .00 0. .00 C

ATOM 2875 CD GLU 184 30. .547 29, .961 1, ,488 0, ,00 0, .00 C

ATOM 2876 OE1 GLU 184 29. .596 29, .338 1, .027 0. .00 0. .00 0

ATOM 2877 OE2 GLU 184 30. ,420 31, .176 2, ,092 0. .00 0. .00 0

ATOM 2878 H GLU 184 30. .148 27, .376 0. .718 0. .00 0. .00 H

ATOM 2879 HA GLU 184 32. ,732 26, .559 -0, .420 0, .00 0. .00 H

ATOM 2880 1HB GLU 184 31. ,974 28, .846 -0, .622 0, .00 0, .00 H

ATOM 2881 2HB GLU 184 33. ,536 28, .734 0, .136 0, .00 0. ,00 H

ATOM 2882 1HG GLU 184 32, ,612 30, .402 1, .429 0, .00 0. .00 H

ATOM 2883 2HG GLU 184 32, .205 29, .042 2, .462 0, .00 0, .00 H

ATOM 2884 N VAL 185 32 ,698 26 .109 2 .850 0 .00 0, .00 N

ATOM 2885 CA VAL 185 33 .408 25 .243 3 .860 0 .00 0, .00 C

ATOM 2886 C VAL .185 33, .357 23 .711 3 .493 0 .00 0. .00 C

ATOM 2887 0 VAL 185 34, .381 23 .026 3 .573 0 .00 0, .00 0

ATOM 2888 CB VAL 185 32 .880 25 .561 5 .307 0 .00 0. .00 c

ATOM 2889 CGI VAL 185 33 .455 24 .659 6 .429 0 .00 0, .00 c

ATOM 2890 CG2 VAL 185 33, .178 27 .008 5 .761 0 .00 0, .00 c

ATOM 2891 H VAL 185 31 .681 26 .263 2 .866 0 .00 0, .00 H

ATOM 2892 HA VAL 185 34. .485 25 .504 3 .851 0 .00 0, .00 H

ATOM 2893 HB VAL 185 31 .778 25 .425 5. .293 0 .00 0, .00 H

ATOM 2894 1HG1 VAL 185 33 .067 24 .928 7 .428 0 .00 0, .00 H

ATOM 2895 2HG1 VAL 185 33 .195 23 .596 6 .261 0 .00 0, .00 H

ATOM 2896 3HG1 VAL 185 34 .560 24 .710 6 .464 0, .00 0, .00 H

ATOM 2897 1HG2 VAL 185 32 .689 27 .263 6 .719 0, .00 0, .00 H

ATOM 2898 2HG2 VAL 185 34, .261 27, .197 5 .876 0, .00 0, .00 H

ATOM 2899 3HG2 VAL 185 32, .813 27 .746 5 .021 0, .00 0, .00 H

ATOM 2900 N LEU 186 32 .189 23 .177 3 .093 0, .00 0, .00 N

ATOM 2901 CA LEU 186 32, .018 21, .751 2 .676 0, .00 0, .00 C

ATOM 2902 C LEU 186 32, .819 21, .315 1, .390 0, .00 0. .00 C

ATOM 2903 0 LEU 186 33 .505 20, .292 1 .418 0, .00 0, .00 0

ATOM 2904 CB LEU 186 30 .490 21, .497 2 .532 0, .00 0. .00 C

ATOM 2905 CG LEU 186 29 .604 21, .650 3, .801 0, .00 0, .00 C

ATOM 2906 CD1 LEU 186 28 .139 21, .868 3, .399 0, .00 0, .00 C

ATOM 2907 CD2 LEU 186 29, .707 20, .438 4, .739 0, .00 0. .00 C

ATOM 2908 H LEU 186 31 .433 23 .863 2 .998 0 .00 0, .00 H

ATOM 2909 HA LEU 186 32 .398 21 .098 3 .488 0 .00 0, .00 H

ATOM 2910 1HB LEU 186 30 .339 20 .479 2 .121 0 .00 0, .00 H

ATOM 2911 2HB LEU 186 30 .116 22 .162 1 .730 0 .00 0, .00 H

ATOM 2912 HG LEU 186 29 .923 22 .553 4, .356 0 .00 0, .00 H

ATOM 2913 1HD1 LEU 186 27 .471 21 .966 4. .273 9 .00 0, .00 H

ATOM 2914 2HD1 LEU 186 28 .014 22 .798 2 .814 0, .00 0, .00 H

ATOM 2915 3HD1 LEU 186 27 .755 21, .041 2 .772 0, .00 0, .00 H

ATOM 2916 1HD2 LEU 186 29 .088 20, .556 5. .646 0, .00 0, .00 H

ATOM 2917 2HD2 LEU 186 29 .385 19, .505 4 .239 0, .00 0, .00 H

ATOM 2918 3HD2 LEU 186 30, .749 20, .279 5, .075 0, .00 0. .00 H

ATOM 2919 N LEU 187 32, .785 22, .103 0, .297 0, .00 0, ,00 N

ATOM 2920 CA LEU 187 33, .779 22. .007 -0, .825 0, ,00 0, ,00 C

ATOM 2921 C LEU 187 35, .279 22. .379 -0, .497 0. ,00 0. ,00 C

ATOM 2922 0 LEU 187 36, .166 22. .035 -1, .280 0, .00 0. .00 0 ATOM 2923 CB LEU 187 33..259 22.,876 -2.,014 0.00 0.,00 c

ATOM 2924 CG LEU 187 31. ,924 22. ,470 -2. ,696 0. 00 0. ,00 c

ATOM 2925 CD1 LEU 187 31. ,455 23, ,565 -3. ,664 0. 00 0. ,00 c

ATOM 2926 CD2 LEU 187 32. ,041 21. .154 -3. .479 0. ,00 0. ,00 C

ATOM 2927 H LEU 187 32, ,179 22. ,930 0. .395 0. 00 0. ,00 H

ATOM 2928 HA LEU 187 33, ,819 20. ,953 -1. .162 0. ,00 0. .00 H

ATOM 2929 1HB LEU 187 34, ,040 22, .913 -2. .799 0. .00 0. .00 H

ATOM 2930 2HB LEU 187 33. .184 23, ,923 -1. .661 0. ,00 0. ,00 H

ATOM 2931 HG LEU 187 31. .145 22, .353 _c -1. .916 0. ,00 0, ,00 H

ATOM 2932 1HD1 LEU 187 30. .494 23, .298 ^' -4. .141 0, .00 0, ,00 H

ATOM 2933 2HD1 LEU 187 31, .299 24, .528 -3. ,142 0. ,00 0. .00 H

ATOM 2934 3HD1 LEU 187 32, ,183 23, .743 -4, .479 0. ,00 0. .00 H

ATOM 2935 1HD2 LEU 187 31, ,080 20, .867 -3, .946 0, .00 0, .00 H

ATOM 2936 2HD2 LEU 187 32. ,794 21. .215 -4. ,288 0. ,00 0. .00 H

ATOM 2937 3HD2 LEU 187 32. .329 20, .315 -2. ,821 0. ,00 0. .00 H

ATOM 2938 N GLN 188 35, .556 23, .081 0, .622 0, ,00 0, .00 N

ATOM 2939 CA GLN 188 36, ,923 23, .476 1, ,085 0. ,00 0, .00 C

ATOM 2940 C GLN 188 37, .582 24, .619 0. .237 0. .00 0. .00 C

ATOM 2941 O GLN 188 38, .423 24 .395 -0, .637 0. .00 0, .00 0

ATOM 2942 CB GLN 188 37, .830 22, .248 1, .400 0. .00 0. ,00 C

ATOM 2943 CG GLN 188 37, .276 21, .310 2. .512 0, .00 0. .00 C

ATOM 2944 CD GLN 188 38, .168 20 .123 2, .860 0, ,00 0, .00 C

ATOM 2945 OE1 GLN 188 39, .053 20, .202 3. .702 0, .00 0, .00 O

ATOM 2946 NE2 GLN 188 37, .958 18 .981 2, .259 0. .00 0, .00 N

ATOM 2947 H GLN 188 34, .733 23 .176 1, .229 0, .00 0, .00 H

ATOM 2948 HA GLN 188 36, .757 23 .932 2, .081 0, ,00 0, .00 H

ATOM 2949 1HB GLN 188 38. .832 22 .608 1, .699 0, .00 0, .00 H

ATOM 2950 2HB GLN 188 38 .005 21 .674 0, .469 0, .00 0, .00 H

ATOM 2951 1HG GLN 188 36, .263 20 .942 2, .246 0, .00 0, .00 H

ATOM 2952 2HG GLN 188 37 .110 21 .880 3, .442 0, .00 0, .00 H

ATOM 2953 1HE2 GLN 188 37 .062 18 .931 1 .762 0, .00 0, .00 H

ATOM 2954 2HE2 GLN 188 38, .472 18 .204 2. .674 0, .00 0, .00 H

ATOM 2955 N SER 189 37 .158 25 .870 0 .505 0, .00 0 .00 N

ATOM 2956 CA SER 189 37. .518 27 .060 -0 .315 0, .00 0, .00 C

ATOM 2957 C SER 189 37, .600 28 .386 0 .535 0, .00 0, .00 C

ATOM 2958 O SER 189 37 .592 28 .377 1 .772 0, .00 0 .00 0

ATOM 2959 CB SER 189 36, .490 27 .114 -1 .486 0. .00 0 .00 C

ATOM 2960 OG SER 189 37, .002 27 .861 -2 .591 0, .00 0 .00 0

ATOM 2961 H SER 189 36 .328 25 .898 1 .114 0, .00 0 .00 H

ATOM 2962 HA SER 189 38, .531 26 .915 -0 .742 0, .00 0 .00 H

ATOM 2963 1HB SER 189 35. .534 27 .554 -1 .139 0, .00 0 .00 H

ATOM 2964 2HB SER 189 36 .218 26 .102 -1 .842 0, .00 0 .00 H

ATOM 2965 HG SER 189 37, .645 27, .302 -3, .047 0, .00 0. .00 H

ATOM 2966 N THR 190 37, .707 29 .549 -0 .133 1, .00 0 .00 N

ATOM 2967 CA THR 190 37 .937 30 .863 0 .539 1, .00 0 .00 C

ATOM 2968 C THR 190 36, .609 31, .531 1, .051 1, .00 0. .00 C

ATOM 2969 O THR 190 35, .966 32 .314 0 .344 1, .00 0 .00 0

ATOM 2970 CB THR 190 38 .772 31 .781 -0 .415 1, .00 0 .00 C

ATOM 2971 OG1 THR 190 39, .981 31 .142 -0 .812 1, .00 0, .00 0

ATOM 2972 CG2 THR 190 39, .224 33 .115 0 .204 1, .00 0, .00 C

ATOM 2973 H THR 190 37 .674 29 .442 -1 .154 1, .00 0 .00 H

ATOM 2974 HA THR 190 38, .588 30, .701 1 .422 1, ,00 0, .00 H

ATOM 2975 HB THR 190 38, .165 31. .995 -1 .320 1, .00 0, .00 H

ATOM 2976 HG1 THR 190 40 .511 31 .813 -1 .247 1, .00 0 .00 H

ATOM 2977 1HG2 THR 190 39, .805 33. .725 -0 .511 1, .00 0. .00 H

ATOM 2978 2HG2 THR 190 38, .361 33 .733 0 .516 1, .00 0. .00 H

ATOM 2979 3HG2 THR 190 39 .855 32 .960 1 .099 1, .00 0 .00 H

ATOM 2980 N TYR 191 36, .194 31, .205 2 .286 0, .00 0. .00 N

ATOM 2981 CA TYR 191 35, .002 31, .816 2 .933 0, .00 0. .00 C

ATOM 2982 C TYR 191 35, .293 33, ,194 3 .651 0, .00 0 .00 C

ATOM 2983 O TYR 191 36, .415 33, ,484 4 .078 0. .00 0. .00 O

ATOM 2984 CB TYR 191 34, .382 30, .736 3 .876 0, .00 0, .00 C

ATOM 2985 CG TYR 191 35, .114 30, .405 5 .194 0, .00 0 .00 C

ATOM 2986 GDI TYR 191 34. .871 31, .165 6, .344 0, .00 0, .00 C

ATOM 2987 CE1 TYR 191 35. .537 30. .873 7 .532 0. .00 0, .00 C ATOM 2988 CZ TYR 191 36.435 29.811 7.584 0.00 0.00 c

ATOM 2989 OH TYR 191 37. 085 29. 514 8. 751 0. 00 0. 00 o

ATOM 2990 CE2 TYR 191 36. 680 29. 048 6. 446 0. 00 0. 00 c

ATOM 2991 CD2 TYR 191 36. 025 29. 345 5. 252 0. 00 0. 00 c

ATOM 2992 H TYR 191 36. 740 30. 454 2. 721 1. 00 0. 00 H

ATOM 2993 HA TYR 191 34. 245 32. 014 2. 146 0. 00 0. ,00 H

ATOM 2994 1HB TYR 191 34. 227 29. 801 3. 302 0. 00 0. ,00 H

ATOM 2995 2HB TYR 191 33. 346 31. 046 4. 113 0. 00 0. ,00 H

ATOM 2996 HD1 TYR 191 34. ,172 31. 991 6. ,310 0. ,00 0. ,00 H

ATOM 2997 HE1 TYR 191 35. 334 31. 478 8. 400 0. 00 0. ,00 H

ATOM 2998 HH TYR 191 36. ,774 30. 135 9. ,415 0. ,00 0, ,00 H

ATOM 2999 HE2 TYR 191 37. 384 28. 230 6. 480 0. ,00 0. ,00 H

ATOM 3000 HD2 TYR 191 36. ,225 28. 751 4. ,369 0. ,00 0, .00 H

ATOM 3001 N ALA 192 34. ,226 33. 991 3. ,845 0. .00 0. ,00 N

ATOM 3002 CA ALA 192 34. 291 35. 295 4. ,562 0. .00 0. ,00 C

ATOM 3003 C ALA 192 32. ,997 35. ,507 5. ,448 0. .00 0. ,00 C

ATOM 3004 O ALA 192 32, ,429 34. .545 5. .975 0, .00 0, ,00 O

ATOM 3005 CB ALA 192 34. ,607 36. ,361 3. .479 0. .00 0, ,00 C

ATOM 3006 H ALA 192 33. ,343 33. .610 3, .490 0. .00 0, ,00 H

ATOM 3007 HA ALA 192 35. .128 35. .287 5, .288 0, .00 0, .00 H

ATOM 3008 1HB ALA 192 34, .751 37. .364 3, .918 0, .00 0, ,00 H

ATOM 3009 2HB ALA 192 35, ,540 36. ,124 2. ,931 0, .00 0, .00 H

ATOM 3010 3HB ALA 192 33, .800 36. .441 2, ,726 0. .00 0, ,00 H

ATOM 3011 N THR 193 32, .494 36. .752 5. ,584 0, .00 0, .00 N

ATOM 3012 CA THR 193 31, .221 37. .057 6, .322 0, .00 0, .00 C

ATOM 3013 C THR 193 29. .910 36. .315 5, ,837 0, .00 0, .00 C

ATOM 3014 O THR 193 29, .251 35. .755 6, .721 0, .00 0. .00 O

ATOM 3015 CB THR 193 31, .006 38 , .594 6, .536 0. .00 0, .00 C

ATOM 3016 OG1 THR 193 31, .049 39. .328 5. .322 0. .00 0, .00 O

ATOM 3017 CG2 THR 193 31, .995 39 , .304 7, .472 0. .00 0, .00 c

ATOM 3018 H THR 193 33, .008 37 .489 5, .096 0 .00 0 .00 H

ATOM 3019 HA THR 193 31, .361 36 , .656 7, .346 0, .00 0, .00 H

ATOM 3020 HB THR 193 30 .000 38 .729 6, .980 0 .00 0 .00 H

ATOM 3021 HG1 THR 193 30 .855 40 .237 5 .569 0 .00 0 .00 H

ATOM 3022 1HG2 THR 193 31, .765 40 .381 7, .582 0 .00 0 .00 H

ATOM 3023 2HG2 THR 193 31 .958 38 .875 8 .492 0 .00 0 .00 H

ATOM 3024 3HG2 THR 193 33, .039 39 .221 7 .119 0 .00 0 .00 H

ATOM 3025 N PRO 194 29 .500 36 .196 .531 0 .00 0 .00 N

ATOM 3026 CA PRO 194 28 .374 35 .306 4 .100 0 .00 0 .00 C

ATOM 3027 CD PRO 194 30 .107 36 .937 3 .406 0 .00 0 .00 C

ATOM 3028 C PRO 194 28 .251 33 .827 4 .603 0 .00 0 .00 C

ATOM 3029 O PRO 194 27 .145 33 .283 4 .562 0 .00 0 .00 O

ATOM 3030 CB PRO 194 28 .505 35 .362 2 .567 0 .00 0 .00 C

ATOM 3031 CG PRO 194 29 .121 36 .721 2 .262 0 .00 0 .00 C

ATOM 3032 HA PRO 194 27 .431 35 .810 4 .390 0 .00 0 .00 H

ATOM 3033 1HD PRO 194 31 .102 36 .522 3 .154 0 .00 0 .00 H

ATOM 3034 2HD PRO 194 30 .224 38 .015 3 .596 0 .00 0 .00 H

ATOM 3035 1HB PRO 194 27 .539 35 .222 2 .047 0 .00 0 .00 H

ATOM 3036 2HB PRO 194 29 .182 34 .561 2 .214 0 .00 0 .00 H

ATOM 3037 1HG PRO 194 28 .338 37 .505 2 .269 0 .00 0 .00 H

ATOM 3038 2HG PRO 194 29 .601 36 .761 1 .266 0 .00 0 .00 H

ATOM 3039 N VAL 195 29 .335 33 .187 5 .086 0 .00 0 .00 N

ATOM 3040 CA VAL 195 29 .289 31 .837 5 .747 0 .00 0 .00 C

ATOM 3041 C VAL 195 28 .181 31 .632 6 .850 0 .00 0 .00 C

ATOM 3042 O VAL 195 27 .426 30 .658 6 .808 0 .00 0 .00 O

ATOM 3043 CB VAL 195 30 .756 31 .427 6 .172 0 .00 0 .00 C

ATOM 3044 CGI VAL 195 31 .167 31 .694 7 .641 0 .00 0 .00 C

ATOM 3045 CG2 VAL 195 31 .045 29 .944 5 .881 0 .00 0 .00 C

ATOM 3046 H VAL 195 30 .151 33 .804 5 .173 0 .00 0 .00 H

ATOM 3047 HA VAL 195 28 .989 31 .147 4 .934 0 .00 0 .00 H

ATOM 3048 HB VAL 195 31 .477 31 .986 5 .540 0 .00 0 .00 H

ATOM 3049 1HG1 VAL 195 32 .235 31 .487 7 .829 0 .00 0 .00 H

ATOM 3050 2HG1 VAL 195 30 .997 32 .755 7 .907 0 .00 0 .00 H

ATOM 3051 3HG1 VAL 195 30 .578 31 .097 8 .365 0 .00 0 .00 H

ATOM 3052 1HG2 VAL 195 32 .070 29 .661 6 .181 0 .00 0 .00 H ATOM 3053 2HG2 VAL 195 30..343 29.,272 6..411 0.00 0.,00 H

ATOM 3054 3HG2 VAL 195 30. .969 29. ,732 4. ,797 0. ,00 0. ,00 H

ATOM 3055 N ASP 196 28, .052 32. .591 7. .781 0. ,00 0. .00 N

ATOM 3056 CA ASP 196 26. ,954 32. .616 8. .793 0. ,00 0. .00 C

ATOM 3057 C ASP 196 25, .518 32. .976 8, .269 0, .00 0, .00 C

ATOM 3058 O ASP 196 24. ,539 32. .583 8. ,903 0. .00 0. ,00 O

ATOM 3059 CB ASP 196 27, .368 33. .608 9. ,909 0, .00 0. .00 C

ATOM 3060 CG ASP 196 28. ,612 33. .242 10, ,711 0. ,00 0. ,00 C

ATOM 3061 OD1 ASP 196 28, .739 32. .201 11. ,343 0, .00 0. .00 O

ATOM 3062 OD2 ASP 196 29, .566 34. ,213 10, ,658 0. ,00 0. ,00 0

ATOM 3063 H ASP 196 28, .752 33, .341 7. ,738 0, ,00 0, .00 H

ATOM 3064 HA ASP 196 26, ,874 31. .611 9, ,255 0, ,00 0, .00 H

ATOM 3065 1HB ASP 195 26. .552 33, ,694 10, ,647 0, ,00 0, .00 H

ATOM 3066 2HB ASP 196 27. ,482 34. .624 9, ,493 0, ,00 0, .00 H

ATOM 3067 N MET 197 25. ,371 33. ,736 7, ,152 1, .00 0. .00 N

ATOM 3068 CA MET 197 24. .052 33. .990 6, ,466 1, ,00 0. .00 C

ATOM 3069 C MET 197 23. ,328 32. ,658 6, ,067 1, ,00 0, .00 C

ATOM 3070 O MET 197 22, ,148 32. .496 6, .391 1, .00 0, .00 O

ATOM 3071 CB MET 197 24. ,224 35. .059 5, ,359 1, .00 0. .00 C

ATOM 3072 CG MET 197 24. ,698 36. .447 5, ,866 1. ,00 0, .00 C

ATOM 3073 SD MET 197 23, .721 37, .039 7, ,269 1, .00 0, .00 S

ATOM 3074 CE MET 197 22, .188 37, .495 6, ,448 1. .00 0, .00 C

ATOM 3075 H MET 197 26, .273 33, .980 6, ,728 1, .00 0, .00 H

ATOM 3076 HA MET 197 23, .381 34, .438 7, ,226 1, .00 0, .00 H

ATOM 3077 1HB MET 197 24, .916 34, .694 4, .579 1, .00 0, .00 H

ATOM 3078 2HB MET 197 23, .256 35, .190 4, ,836 1. .00 0, ,00 H

ATOM 3079 1HG MET 197 25, .753 36. .396 6. .193 1, .00 0, .00 H

ATOM 3080 2HG MET 197 24, .676 37, .199 5, ,059 1, .00 0, .00 H

ATOM 3081 1HE MET 197 22, .377 38, .258 5. .673 1, .00 0, .00 H

ATOM 3082 3HE MET 197 21 .717 36 .620 5, .965 1, .00 0, .00 H

ATOM 3083 2HE MET 197 21, .470 37, .911 7. ,173 1. .00 0, .00 H

ATOM 3084 N TRP 198 24 .008 31 .730 5. ,357 0, .00 0, .00 N

ATOM 3085 CA TRP 198 23 .482 30, .344 5, ,174 0, .00 0, .00 C

ATOM 3086 C TRP 198 23 .039 29 .624 6, ,501 0, .00 0, .00 C

ATOM 3087 O TRP 198 21, .936 29 .078 6, ,540 0, .00 0, .00 O

ATOM 3088 CB TRP 198 24 .555 29 .549 4, ,380 0, .00 0, .00 C

ATOM 3089 CG TRP 198 24 .106 28 .154 3, .916 0 .00 0 .00 C

ATOM 3090 GDI TRP 198 24 .021 26 .996 4, ,724 0, .00 0, .00 C

ATOM 3091 NE1 TRP 198 23 .472 25 .908 4, .022 0 .00 0 .00 N

ATOM 3092 CE2 TRP 198 23 .231 26 .417 2, ,751 0, .00 0, .00 C

ATOM 3093 CD2 TRP 198 23 .633 27 .774 2, .676 0 .00 0 .00 C

ATOM 3094 CE3 TRP 198 23 .481 28 .493 1, .462 0, .00 0, .00 C

ATOM 3095 CZ3 TRP 198 22 .917 27 .833 0. .370 0, .00 0 .00 C

ATOM 3096 CH2 TRP 198 22 .487 26 .507 0. .466 0, .00 0, .00 C

ATOM 3097 CZ2 TRP 198 22 .639 25 .786 1, .650 0. .00 0, .00 C

ATOM 3098 H TRP 198 25 .006 31 .961 5, .292 0 .00 0 .00 H

ATOM 3099 HA TRP 198 22 .573 30 .417 4, .540 0, .00 0, .00 H

ATOM 3100 1HB TRP 198 25 .475 29 .453 4, .989 0 .00 0 .00 H

ATOM 3101 2HB TRP 198 24 .859 30 .128 3. .492 0, .00 0, .00 H

ATOM 3102 HD1 TRP 198 24 .311 26 .960 5, .766 0, .00 0 .00 H

ATOM 3103 HE1 TRP 198 23 .325 24 .947 4. .352 0, .00 0, .00 H

ATOM 3104 HE3 TRP 198 23 .760 29 .534 1. .387 0, .00 0, .00 H

ATOM 3105 HZ3 TRP 198 22 .771 28 .358 -0. .560 0, .00 0, .00 H

ATOM 3106 HH2 TRP 198 22 .021 26 .037 -0, .386 0, .00 0, .00 H

ATOM 3107 HZ2 TRP 198 22 .292 24 .769 1, .720 0, .00 0 .00 H

ATOM 3108 N SER 199 23 .865 29 .620 7. .569 0. .00 0, .00 N

ATOM 3109 CA SER 199 23 .454 29 .119 8, .917 0, .00 0, .00 C

ATOM 3110 C SER 199 22 .151 29, .760 9. .521 0. ,00 0, .00 C

ATOM 3111 O SER 199 21 .274 29 .019 9, .966 0. .00 0, .00 O

ATOM 3112 CB SER 199 24, .649 29, .237 9. .898 0, ,00 0, .00 C

ATOM 3113 OG SER 199 25 .849 28, .629 9. .410 0, ,00 0, .00 O

ATOM 3114 H SER 199 24, .739 30, .145 7. .444 0. ,00 0. ,00 H

ATOM 3115 HA SER 199 23, .236 28, .039 8. .813 0, ,00 0, .00 H

ATOM 3116 1HB SER 199 24 .385 28, .791 10, .878 0, ,00 0, .00 H

ATOM 3117 2HB SER 199 24, .859 30. .301 10. .122 0. ,00 0. .00 H ATOM 3118 HG SER 199 25.,632 27..723 9,.140 o..00 0..00 H

ATOM 3119 N VAL 200 21. ,981 31. ,098 9. .462 o. .00 0. .00 N

ATOM 3120 CA VAL 200 20. ,663 31. ,779 9, .707 o. .00 0, .00 C

ATOM 3121 C VAL 200 19. ,487 31. ,282 8, .782 o, .00 0. .00 C

ATOM 3122 O VAL 200 18. ,401 31. ,037 9, ,302 o. .00 0. .00 0

ATOM 3123 CB VAL 200 20. ,839 33. ,343 9. .702 o. .00 0. ,00 C

ATOM 3124 CGI VAL 200 19. ,533 34. .132 9, .958 o. .00 0, ,00 C

ATOM 3125 CG2 VAL 200 21. ,837 33. .879 10. .754 o. .00 0. .00 C

ATOM 3126 H VAL 200 22. .805 31. .610 9. .112 o, .00 0, .00 H

ATOM 3127 HA VAL 200 20, .351 31. .509 10, .736 o. .00 0, .00 H

ATOM 3128 HB VAL 200 21, .214 33. .635 8, .699 o, .00 0, .00 H

ATOM 3129 1HG1 VAL 200 19. .687 35. ,226 9, .934 o. .00 0. .00 H

ATOM 3130 2HG1 VAL 200 18, .764 33. ,916 9, .193 o. .00 0, .00 H

ATOM 3131 3HG1 VAL 200 19. .089 33. ,889 10, .943 O, .00 0, ,00 H

ATOM 3132 1HG2 VAL 200 21, ,946 34. ,979 10, .713 o. .00 0, .00 H

ATOM 3133 2HG2 VAL 200 21. ,541 33. ,615 11, ,787 o, .00 0. ,00 H

ATOM 3134 3HG2 VAL 200 22, ,851 33. .471 10, .596 o. ,00 0. .00 H

ATOM 3135 N GLY 201 19. .678 31. ,091 7. .461 o. .00 0, .00 N

ATOM 3136 CA GLY 201 18. .717 30. ,333 6. .597 o. .00 0, .00 C

ATOM 3137 C GLY 201 18, ,281 28. ,902 7. .018 o. .00 0, .00 C

ATOM 3138 O GLY 201 17, .085 28. ,610 7. .036 o. .00 0, .00 O

ATOM 3139 H GLY 201 20. .626 31. ,356 7. .154 o. .00 0, .00 H

ATOM 3140 1HA GLY 201 19. ,143 30. .259 5, .581 o , .00 0, .00 H

ATOM 3141 2HA GLY 201 17, ,802 30, .941 6, .467 o. .00 0, .00 H

ATOM 3142 N CYS 202 19, ,228 28. .025 7, .382 o, .00 0, ,00 N

ATOM 3143 CA CYS 202 18, ,915 26. .730 8, .058 o, .00 0, ,00 C

ATOM 3144 C CYS 202 18, .140 26, .822 9, .426 0, .00 0. ,00 C

ATOM 3145 O CYS 202 17, .170 26, .088 9, .631 o, .00 0, ,00 0

ATOM 3146 CB CYS 202 20, .247 25. .960 8, .200 o, .00 0. ,00 C

ATOM 3147 SG CYS 202 20, .923 25. ,474 6, .576 o, .00 0, .00 S

ATOM 3148 H CYS 202 20, .176 28. .426 7, .356 o, .00 0, .00 H

ATOM 3149 HA CYS 202 18, .263 26. .141 7, .384 o, .00 0. .00 H

ATOM 3150 1HB CYS 202 20, .092 25. .035 8, .786 o, .00 0. .00 H

ATOM 3151 2HB CYS 202 20, .999 26. .552 8, .757 o, .00 0. .00 H

ATOM 3152 HG CYS 202 21, .385 26, .664 6 .205 1, .00 0, .00 H

ATOM 3153 N ILE 203 18 .529 27, .744 10, .328 o .00 0, .00 N

ATOM 3154 CA ILE 203 17 .747 28, .087 11 .563 o .00 0, .00 C

ATOM 3155 C ILE 203 16 .316 28, .672 11 .256 o .00 0, .00 C

ATOM 3156 O ILE 203 15 .347 28, .187 11 .835 o .00 0, .00 0

ATOM 3157 CB ILE 203 18 .641 28, .976 12 .511 o. .00 0, .00 C

ATOM 3158 CG2 ILE 203 17 .883 29, .520 13, .753 0 .00 0, .00 C

ATOM 3159 CGI ILE 203 19 .920 28, .240 13 .025 0 .00 0, .00 C

ATOM 3160 GDI ILE 203 21 .102 29, .166 13 .362 o .00 0, .00 C

ATOM 3161 H ILE 203 19 .350 28, .293 10 .040 o .00 0, .00 H

ATOM 3162 HA ILE 203 17 .557 27, .143 12 .113 o .00 0, .00 H

ATOM 3163 HB ILE 203 18 .960 29 .854 11 .913 o .00 0, .00 H

ATOM 3164 1HG2 ILE 203 18 .519 30 .158 14 .395 o .00 0, .00 H

ATOM 3165 2HG2 ILE 203 17 .017 30 .145 13 .468 o .00 0, .00 H

ATOM 3166 3HG2 ILE 203 17 .492 28 .705 14 .391 o .00 0, .00 H

ATOM 3167 1HG1 ILE 203 20 .288 27, .521 12 .270 0 .00 0, .00 H

ATOM 3168 2HG1 ILE 203 19 .673 27, .606 13 .897 o .00 0, .00 H

ATOM 3169 1HD1 ILE 203 21 .942 28 .613 13 .822 0 .00 0, .00 H

ATOM 3170 2HD1 ILE 203 21 .501 29 .671 12 .464 0 .00 0, .00 H

ATOM 3171 3HD1 ILE 203 20 .809 29, .962 14 .067 0 .00 0, .00 H

ATOM 3172 N PHE 204 16 .161 29 .661 10 .356 O .00 0, .00 N

ATOM 3173 CA PHE 204 14 .837 30, .172 9, .875 0 .00 0, .00 C

ATOM 3174 C PHE 204 13 .787 29. .111 9 .392 O .00 0, .00 C

ATOM 3175 O PHE 204 12 .634 29, .150 9 .829 0. .00 0, .00 0

ATOM 3176 CB PHE 204 15 .161 31, .221 8, .766 0. .00 0, .00 C

ATOM 3177 CG PHE 204 14 .078 32, .192 8, .247 o. .00 0, ,00 C

ATOM 3178 CD1 PHE 204 12 .884 32, .455 8, .930 o. .00 0, .00 C

ATOM 3179 CE1 PHE 204 12 .001 33, .425 8, .459 o. .00 0. .00 C

ATOM 3180 CZ PHE 204 12 .296 34. .129 7. .296 o. .00 0. .00 C

ATOM 3181 CE2 PHE 204 13 .470 33. .866 6. ,601 o, .00 0. .00 C

ATOM 3182 CD2 PHE 204 14 .364 32. .910 7, ,078 o. .00 0. .00 C ATOM 3183 H PHE 204 17.049 29.996 9..953 0.00 0.00 H

ATOM 3184 HA PHE 204 14. 372 30. ,701 10. .730 0. ,00 0. 00 H

ATOM 3185 1HB PHE 204 15. 599 30. ,680 7. ,905 0. .00 0. ,00 H

ATOM 3186 2HB PHE 204 15. 991 31. ,864 9. ,107 0. ,00 0. .00 H

ATOM 3187 HD1 PHE 204 12. 634 31. ,931 9, .841 0. ,00 0. ,00 H

ATOM 3188 HE1 PHE 204 11. 089 33. ,637 8, .995 0. ,00 0. ,00 H

ATOM 3189 HZ PHE 204 11. 605 34. ,870 6. .920 0. ,00 0. ,00 H

ATOM 3190 HE2 PHE 204 13. 686 34. ,405 5. .691 0. ,00 0. ,00 H

ATOM 3191 HD2 PHE 204 15. ,280 32. ,735 6, .532 0. .00 0. ,00 H

ATOM 3192 N ALA 205 14. ,187 28. ,152 8, .541 0. .00 0. .00 N

ATOM 3193 CA ALA 205 13. ,370 26, .944 8. ,253 0. .00 0. ,00 C

ATOM 3194 C ALA 205 13. .031 26, .014 9, ,470 0. .00 0. ,00 C

ATOM 3195 O ALA 205 11. ,865 25, .656 9, ,645 0. .00 0, ,00 O

ATOM 3196 CB ALA 205 14. ,122 26, .218 7, .129 0. ,00 0. ,00 C

ATOM 3197 H ALA 205 15, ,177 28, .233 8, .274 0. ,00 0. ,00 H

ATOM 3198 HA ALA 205 12, .397 27, .286 7, .847 0. .00 0, ,00 H

ATOM 3199 1HB ALA 205 13. .555 25, .343 6, .775 0. .00 0. .00 H

ATOM 3200 2HB ALA 205 14. .281 26, .867 6, .246 0. .00 0. .00 H

ATOM 3201 3HB ALA 205 15. .116 25. .863 7, .463 0. .00 0. .00 H

ATOM 3202 N GLU 206 14. .009 25. .683 10, .333 0. .00 0, .00 N

ATOM 3203 CA GLU 206 13. .752 25. .041 11, .656 0. .00 0, .00 C

ATOM 3204 C GLU 206 12. .868 25. .828 12, .701 0. .00 0, .00 C

ATOM 3205 O GLU 206 12, .249 25, .181 13, .546 0. .00 0, .00 O

ATOM 3206 CB GLU 206 15, .148 24, .634 12 .194 0, .00 0, .00 C

ATOM 3207 CG GLU 206 15, .120 23, .762 13 .476 0, ,00 0, .00 c

ATOM 3208 CD GLU 206 16, .457 23, .169 13 .896 0. .00 0, .00 c

ATOM 3209 OE1 GLU 206 17, .471 23, .184 13 .206 0. .00 0, .00 o

ATOM 3210 OE2 GLU 206 16, .401 22, .596 15 .127 0. .00 0, .00 0

ATOM 3211 H GLU 206 14, .918 26, .119 10 .129 0, .00 0, .00 H

ATOM 3212 HA GLU 206 13, .206 24, .098 11 .463 0, .00 0. .00 H

ATOM 3213 1HB GLU 206 15, .760 25. .537 12 .386 0, .00 0, .00 H

ATOM 3214 2HB GLU 206 15, .700 24, .075 11 .412 0, .00 0 .00 H

ATOM 3215 1HG GLU 206 14 .419 22 .922 13 .383 0, .00 0 .00 H

ATOM 3216 2HG GLU 206 14 .752 24 .356 14 .330 0, .00 0 .00 H

ATOM 3217 N MET 207 1 .744 27 .168 12 .655 0. .00 0 .00 N

ATOM 3218 CA MET 207 11 .699 27 .914 13 .426 0, .00 0 .00 C

ATOM 3219 C MET 207 10 .213 27 .570 13 .030 0, .00 0 .00 C

ATOM 3220 O MET 207 9 .387 27 .339 13 .915 0, .00 0 .00 O

ATOM 3221 CB MET 207 11 .960 29 .445 13 .350 0, .00 0 .00 C

ATOM 3222 CG MET 207 13 .273 29 .984 13 .966 0, .00 0 .00 C

ATOM 3223 SD MET 207 13 .449 29 .486 15 .691 0, .00 0 .00 S

ATOM 3224 CE MET 207 12 .605 30 .843 16 .515 0, .00 0 .00 C

ATOM 3225 H MET 207 13 .423 27 .631 12 .035 0, .00 0 .00 H

ATOM 3226 HA MET 207 11 .793 27 .625 14 .491 0, .00 0 .00 H

ATOM 3227 1HB MET 207 11 .124 29 .960 13 .860 0, .00 0 .00 H

ATOM 3228 2HB MET 207 11 .890 29 .781 12 .297 0, .00 0 .00 H

ATOM 3229 1HG MET 207 13 .327 31 .086 13 .883 0, .00 0 .00 H

ATOM 3230 2HG MET 207 14 .148 29 .605 13 .412 0, .00 0 .00 H

ATOM 3231 1HE MET 207 12 .584 30 .672 17 .606 0, .00 0 .00 H

ATOM 3232 2HE MET 207 13 .124 31 .801 16 .328 0, .00 0 .00 H

ATOM 3233 3HE MET 207 11 .564 30 .938 16 .160 0, .00 0 .00 H

ATOM 3234 N PHE 208 9 .877 27 .503 11 .728 0, .00 0 .00 N

ATOM 3235 CA PHE 208 8 .558 26 .979 11 .247 0, .00 0 .00 C

ATOM 3236 C PHE 208 8 .375 25 .417 11 .303 0, .00 0 .00 C

ATOM 3237 O PHE 208 7 .280 24 .948 11 .615 0, .00 0 .00 O

ATOM 3238 CB PHE 208 8 .292 27 .530 9 .814 0, .00 0 .00 C

ATOM 3239 CG PHE 208 7 .993 29 .039 9 .734 0, .00 0 .00 C

ATOM 3240 CD1 PHE 208 6 .685 29 .506 9 .909 0, .00 0 .00 C

ATOM 3241 CE1 PHE 208 6 .417 30 .873 9 .869 0, .00 0 .00 C

ATOM 3242 CZ PHE 208 7 .450 31 .779 9 .653 0, .00 0 .00 C

ATOM 3243 CE2 PHE 208 8 .753 31 .322 9 .472 0, .00 0 .00 C

ATOM 3244 CD2 PHE 208 9 .025 29 .956 9 .513 0, .00 0 .00 C

ATOM 3245 H PHE 208 10 .650 27 .747 11 .097 0, .00 0, .00 H

ATOM 3246 HA PHE 208 7 .759 27 .385 11 .903 0, .00 0. .00 H

ATOM 3247 1HB PHE 208 7 .431 26, .994 9 .367 0, .00 0, .00 H ATOM 3248 2HB PHE 208 9.134 27.,272 9.143 0.00 0.00 H

ATOM 3249 HD1 PHE 208 5. 870 28. ,814 10. ,070 0. ,00 0. ,00 H

ATOM 3250 HE1 PHE 208 5. 404 31, ,229 9. .993 0. .00 0. ,00 H

ATOM 3251 HZ PHE 208 7. .236 32. ,838 9. .610 0. ,00 0. ,00 H

ATOM 3252 HE2 PHE 208 9. ,549 32. ,026 9. ,294 0. ,00 0. ,00 H

ATOM 3253 HD2 PHE 208 10. ,042 29. .617 9. ,378 0, ,00 0, .00 H

ATOM 3254 N ARG 209 9. ,385 24, .600 11, ,004 0, .00 0. .00 N

ATOM 3255 CA ARG 209 9. ,271 23, .114 11. ,088 0, ,00 0. ,00 C

ATOM 3256 C ARG 209 9. ,642 22. ,412 12. .444 0, .00 0, ,00 C

ATOM 3257 O ARG 209 9. ,362 21. .215 12, .562 0, .00 0. .00 O

ATOM 3258 CB ARG 209 10. ,345 22. .589 10. ,073 0. .00 0. .00 C

ATOM 3259 CG ARG 209 10. ,124 22, ,754 8, .546 0. .00 0. ,00 c

ATOM 3260 CD ARG 209 11, ,425 22, ,617 7. ,717 0. .00 0. .00 c

ATOM 3261 NE ARG 209 12, ,145 21, ,330 7, .942 0, .00 0, .00 N

ATOM 3262 CZ ARG 209 12. ,206 20. ,295 7. .117 0. ,00 0, .00 C

ATOM 3263 NH1 ARG 209 11. ,625 20. ,242 5. ,956 0. ,00 0. .00 N

ATOM 3264 NH2 ARG 209 12. ,903 19. ,282 7. ,498 0. ,00 0. .00 N

ATOM 3265 H ARG 209 10. ,245 25, ,098 10. ,730 0. ,00 0, .00 H

ATOM 3266 HA ARG 209 8, ,262 22, .768 10. .784 0. ,00 0, .00 H

ATOM 3267 1HB ARG 209 10, ,495 21. .503 10. .231 0, ,00 0, ,00 H

ATOM 3268 2HB ARG 209 11, .327 23. .032 10, .347 0. ,00 0. ,00 H

ATOM 3269 1HG ARG 209 9, .695 23. .760 8, .352 0. .00 0, ,00 H

ATOM 3270 2HG ARG 209 9, .345 22. .050 8, .193 0, .00 0, .00 H

ATOM 3271 1HD ARG 209 12. .100 23, .455 7. .999 0, .00 0. .00 H

ATOM 3272 2HD ARG 209 11. .211 22. ,821 6. .646 0, .00 0 , .00 H

ATOM 3273 HE ARG 209 12, ,695 21. .229 8. ,805 1, .00 0, .00 H

ATOM 3274 1HH1 ARG 209 11, .753 19. .427 5, ,359 0. ,00 0, .00 H

ATOM 3275 2HH1 ARG 209 11, .127 21. .103 5, .699 0. .00 0, .00 H

ATOM 3276 1HH2 ARG 209 13, .040 18. .549 6. .803 0, ,00 0, .00 H

ATOM 3277 2HH2 ARG 209 13, .445 19, .431 8, .354 0, .00 0, .00 H

ATOM 3278 N ARG 210 10, .229 23, .087 13, .462 0, .00 0, .00 N

ATOM 3279 CA ARG 210 10, .838 22, .389 14, .651 0, .00 0 .00 C

ATOM 3280 C ARG 210 11 .834 21, .186 14, .392 0, .00 0 .00 C

ATOM 3281 O ARG 210 12 .198 20, .460 15, .320 0, .00 0 .00 O

ATOM 3282 CB ARG 210 9 .769 22 .116 15 .752 0, .00 0 .00 C

ATOM 3283 CG ARG 210 9 .214 23 .383 16 .454 0, .00 0 .00 C

ATOM 3284 CD ARG 210 8 .120 23 .103 17 .497 0, .00 0 .00 C

ATOM 3285 NE ARG 210 6 .841 22 .743 16 .825 0, .00 0 .00 N

ATOM 3286 CZ ARG 210 5 .981 21 .811 17 .219 0 .00 0 .00 C

ATOM 3287 NH1 ARG 210 6 .120 21 .081 18 .284 0, .00 0 .00 N

ATOM 3288 NH2 ARG 210 4 .934 21 .628 16 .495 0 .00 0 .00 N

ATOM 3289 H ARG 210 10 .433 24 .077 13 .261 0 .00 0 .00 H

ATOM 3290 HA ARG 210 11 .530 23 .134 15 .094 0 .00 0 .00 H

ATOM 3291 1HB ARG 210 10 .210 21 .468 16 .536 0 .00 0 .00 H

ATOM 3292 2HB ARG 210 8 .950 21 .516 15 .314 0 .00 0 .00 H

ATOM 3293 1HG ARG 210 8 .862 24 .126 15 .707 0 .00 0 .00 H

ATOM 3294 2HG ARG 210 10 .056 23 .898 16 .963 0 .00 0 .00 H

ATOM 3295 1HD ARG 210 7 .965 24 .029 18 .086 0 .00 0 .00 H

ATOM 3296 2HD ARG 210 8 .490 22 .354 18 .230 0 .00 0 .00 H

ATOM 3297 HE ARG 210 6 .587 23 .203 15 .944 1 .00 0 .00 H

ATOM 3298 1HH1 ARG 210 5 .376 20 .440 18 .549 0 .00 0 .00 H

ATOM 3299 2HH1 ARG 210 6 .927 21 .344 18 .859 0 .00 0 .00 H

ATOM 3300 1HH2 ARG 210 4 .261 20 .937 16 .821 0 .00 0 .00 H

ATOM 3301 2HH2 ARG 210 4 .802 22 .278 15 .712 0 .00 0 .00 H

ATOM 3302 N LYS 211 12 .332 21 .018 13 .154 0 .00 0 .00 N

ATOM 3303 CA LYS 211 13 .252 19 .921 12 .751 0 .00 0 .00 C

ATOM 3304 C LYS 211 14 .447 20 .489 11 .887 0 .00 0 .00 C

ATOM 3305 O LYS 211 14 .206 21 .367 11 .048 0 .00 0 .00 O

ATOM 3306 CB LYS 211 12 .398 18 .860 11 .999 0 .00 0 .00 C

ATOM 3307 CG LYS 211 13 .150 17 .552 11 .655 0 .00 0 .00 C

ATOM 3308 CD LYS 211 12 .233 16 .490 11 .022 0 .00 0 .00 C

ATOM 3309 CE LYS 211 12 .984 15 .184 10 .733 0 .00 0 .00 C

ATOM 3310 NZ LYS 211 12 .041 14 .187 10, .187 0, .00 0, .00 N

ATOM 3311 H LYS 211 12 .027 21 .763 12, .520 0, .00 0, .00 H

ATOM 3312 HA LYS 211 13 .663 19, .450 13, .664 0. .00 0, .00 H ATOM 3313 1HB LYS 211 11.,964 19.,318 11,.089 0.,00 0.,00 H

ATOM 3314 2HB LYS 211 11. ,521 18. ,615 12. .636 0. .00 0. ,00 H

ATOM 3315 1HG LYS 211 13. ,604 17. .155 12. .587 0. .00 0. .00 H

ATOM 3316 2HG LYS 211 14. ,007 17, .783 10. .987 0. .00 0. .00 H

ATOM 3317 1HD LYS 211 11. ,779 16, .907 10. .099 0. .00 0. .00 H

ATOM 3318 2HD LYS 211 11. ,380 16, .310 11. ,712 0. .00 0. .00 H

ATOM 3319 1HE LYS 211 13. ,468 14, .811 11. .669 0. .00 0. .00 H

ATOM 3320 2HE LYS 211 13. ,835 15. ,375 10, ,036 0. .00 0, .00 H

ATOM 3321 1HZ LYS 211 12. ,467 13. .274 9, ,976 1. .00 0, .00 H

ATOM 3322 2HZ LYS 211 11. ,269 13. .985 10, .840 1. .00 0, .00 H

ATOM 3323 3HZ LYS 211 11. ,577 14, ,496 9, ,322 1. .00 0, .00 H

ATOM 3324 N PRO 212 15. ,734 20. .035 12, .013 0. .00 0. .00 N

ATOM 3325 CA PRO 212 16. ,825 20. ,416 11, .066 0. .00 0, .00 C

ATOM 3326 CD PRO 212 16. ,194 19. ,165 13, .113 0. .00 0, .00 C

ATOM 3327 C PRO 212 16, ,552 20. .186 9 .539 0, .00 0, .00 C

ATOM 3328 O PRO 212 16, ,242 19, .070 9 .111 0, .00 0, .00 O

ATOM 3329 CB PRO 212 18, ,010 19, .571 11, .581 0. .00 0, .00 C

ATOM 3330 CG PRO 212 17, ,711 19, .315 13 .056 0. .00 0, .00 C

ATOM 3331 HA PRO 212 17, ,057 21, .487 11 .254 0. ,00 0, .00 H

ATOM 3332 1HD PRO 212 15. ,880 18, .117 12 .955 0, .00 0, .00 H

ATOM 3333 2HD PRO 212 15. .821 19, .503 14, .103 0. .00 0, .00 H

ATOM 3334 1HB PRO 212 18. ,975 20, .095 11, .439 0, .00 0, .00 H

ATOM 3335 2HB PRO 212 18, .091 18, .608 11, .041 0, ,00 0, .00 H

ATOM 3336 1HG PRO 212 18, .020 20, .200 13 .654 0. ,00 0, .00 H

ATOM 3337 2HG PRO 212 18, ,243 18, .437 13 .458 0. ,00 0, .00 H

ATOM 3338 N LEU 213 16. .693 21, .249 8, .729 0. ,00 0, .00 N

ATOM 3339 CA LEU 213 16. .426 21, .188 7. .258 0. ,00 0, ,00 C

ATOM 3340 C LEU 213 17. .330 20, .211 6, .418 0, ,00 0, .00 C

ATOM 3341 O LEU 213 16, .816 19, .482 5, .566 0. ,00 0. .00 O

ATOM 3342 CB LEU 213 16, ,480 22, .655 6, .726 0. .00 0, .00 C

ATOM 3343 CG LEU 213 15, .946 22 .897 5 .287 0, .00 0, .00 C

ATOM 3344 CD1 LEU 213 14, .420 22 .725 5 .211 0, .00 0, .00 C

ATOM 3345 CD2 LEU 213 16, .344 24 .296 4 .792 0, .00 0, .00 C

ATOM 3346 H LEU 213 16, .845 22 .134 9 .231 0, .00 0, .00 H

ATOM 3347 HA LEU 213 15, .390 20 .831 7 .125 0, .00 0, .00 H

ATOM 3348 1HB LEU 213 17, .531 23 .005 6 .782 0, .00 0, .00 H

ATOM 3349 2HB LEU 213 15, .936 23 .336 7 .413 0, .00 0, .00 H

ATOM 3350 HG LEU 213 16, .418 22 .172 4 .591 0, .00 0, .00 H

ATOM 3351 1HD1 LEU 213 14, .009 23 .057 4 .240 0, .00 0, .00 H

ATOM 3352 2HD1 LEU 213 14, .131 21 .668 5. .325 0, .00 0, .00 H

ATOM 3353 3HD1 LEU 213 13, .893 23, .302 5. .990 0, .00 0, .00 H

ATOM 3354 1HD2 LEU 213 15, .946 24, .513 3, .783 0, .00 0, .00 H

ATOM 3355 2HD2 LEU 213 15, .994 25, .105 5, .456 0, .00 0, .00 H

ATOM 3356 3HD2 LEU 213 17, .443 24, .402 4, .719 0, .00 0, .00 H

ATOM 3357 N PHE 214 18, .660 20, .214 6, .633 0, .00 0, ,00 N

ATOM 3358 CA PHE 214 19, .619 19, .379 5, .855 0, .00 0, ,00 C

ATOM 3359 C PHE 214 20 .289 18 .310 6 .780 0, .00 0, .00 C

ATOM 3360 O PHE 214 21 .242 18 .611 7 .507 0, .00 0, .00 O

ATOM 3361 CB PHE 214 20 .684 20 .290 5 .173 0, .00 0, .00 C

ATOM 3362 CG PHE 214 20 .203 21 .402 4 .222 0, .00 0, .00 C

ATOM 3363 CD1 PHE 214 19, .422 21 .100 3 .101 0, .00 0, .00 C

ATOM 3364 CE1 PHE 214 19, .010 22 .111 2 .242 0, .00 0, .00 C

ATOM 3365 CZ PHE 214 19, .383 23, .431 2, .480 0, .00 0, ,00 C

ATOM 3366 CE2 PHE 214 20, .157 23, .742 3 .597 0, .00 0, ,00 C

ATOM 3367 CD2 PHE 214 20, .563 22, .732 4, .465 0, ,00 0, ,00 C

ATOM 3368 H PHE 214 18, .965 20, .880 7, .351 0. .00 0. ,00 H

ATOM 3369 HA PHE 214 19, .102 18, .844 5, .032 0, ,00 0. .00 H

ATOM 3370 1HB PHE 214 21, .389 19, .651 4, .605 0, .00 0. .00 H

ATOM 3371 2HB PHE 214 21, .317 20, ,732 5, .968 0. .00 0. ,00 H

ATOM 3372 HD1 PHE 214 19, ,143 20. .079 2. .880 0. .00 0, ,00 H

ATOM 3373 HE1 PHE 214 18. .424 21. .858 1. .373 0. ,00 0, ,00 H

ATOM 3374 HZ PHE 214 19. .070 24. .214 1. .803 0. ,00 0. ,00 H

ATOM 3375 HE2 PHE 214 20, .443 24, .767 3, .787 0, ,00 0. .00 H

ATOM 3376 HD2 PHE 214 21, .169 22, .987 5, .323 0. .00 0. .00 H

ATOM 3377 N CYS 215 19, .808 17, .054 6, .744 1. .00 0, .00 N ATOM 3378 CA CYS 215 20.369 15.951 7.578 1.00 00 c

ATOM 3379 C CYS 215 21.578 15.187 6.921 1.00 00 c

ATOM 3380 0 CYS 215 21.495 14.012 6.549 00 00 o

ATOM 3381 CB CYS 215 19.167 15.055 7.948 00 00 c

ATOM 3382 SG CYS 215 17.930 15.973 8.934 00 00 s

ATOM 3383 H CYS 215 18.960 16.948 6.183 00 00 H

ATOM 3384 HA CYS 215 20.745 16.361 8.536 00 0.00 H

ATOM 3385 1HB CYS 215 18.690 14.630 7.045 00 0.00 H

ATOM 3386 2HB CYS 215 19.514 14.189 8.543 00 00 H

ATOM 3387 HG CYS 215 18.712 16.220 9.984 00 00 H

ATOM 3388 N GLY 216 22.725 15.873 6.809 00 00 N

ATOM 3389 CA GLY 216 23.950 15.323 6.178 00 00 c

ATOM 3390 C GLY 216 25.054 14.880 .159 00 00 c

ATOM 3391 0 GLY 216 25.614 15.693 .895 00 00 o

ATOM 3392 H GLY 216 22.649 16.870 .059 00 00 H

ATOM 3393 1HA GLY 216 24.393 16.109 .553 00 00 H

ATOM 3394 2HA GLY 216 23.712 14.524 5.448 00 00 H

ATOM 3395 N ASN 217 25.398 13.588 7.126 00 00 N

ATOM 3396 CA ASN 217 26.496 13.009 7.959 00 00 c

ATOM 3397 C ASN 217 27.972 13.366 7.538 00 00 c

ATOM 3398 0 ASN 217 28.757 13.811 8.379 00 00 o

ATOM 3399 CB ASN 217 26.219 11.484 8.129 00 00 c

ATOM 3400 CG ASN 217 26.228 10.576 6.887 00 00 c

ATOM 3401 OD1 ASN 217 26.353 10.989 5.740 00 00 o

ATOM 3402 ND2 ASN 217 26.078 9.291 7.069 00 00 N

ATOM 3403 H ASN 217 24.948 13.059 6.363 00 0.00 H

ATOM 3404 HA ASN 217 26.397 13.440 8.976 00 0.00 H

ATOM 3405 1HB ASN 217 26.954 11.083 8.851 00 00 H

ATOM 3406 2HB ASN 217 25.238 11.360 8.624 00 00 H

ATOM 3407 1HD2 ASN 217 26.064 8.769 6.187 00 00 H

ATOM 3408 2HD2 ASN 217 25.971 .953 8.026 00 00 H

ATOM 3409 N SER 218 28.351 13.152 .267 00 00 N

ATOM 3410 CA SER 218 29.687 13.528 .714 00 00 c

ATOM 3411 C SER 218 29.591 14.675 .646 00 00 c

ATOM 3412 0 SER 218 28.507 15.003 .157 0.00 00 o

ATOM 3413 CB SER 218 30.314 12.218 .175 0.00 00 c

ATOM 3414 OG SER 218 31.674 12.431 .790 00 00 o

ATOM 3415 H SER 218 27.593 12.780 .676 00 00 H

ATOM 3416 HA SER 218 30.348 13.902 .521 00 00 H

ATOM 3417 1HB SER 218 29.728 11.834 .316 00 00 H

ATOM 3418 2HB SER 218 30.276 11.426 .949 00 0.00 H

ATOM 3419 HG SER 218 32.042 11.577 .541 00 0.00 H

ATOM 3420 N GLU 219 30.723 15.302 4.266 00 00 3sr

ATOM 3421 CA GLU 219 30.726 16.524 3.391 00 00 c

ATOM 3422 C GLU 219 30.042 16.396 1.,982 00 00 c

ATOM 3423 0 GLU 219 29.211 17.239 1.,639 00 00 o

ATOM 3424 CB GLU 219 32.162 17.112 3.,276 00 00 c

ATOM 3425 CG GLU 219 32.778 17.676 4..585 00 00 c

ATOM 3426 CD GLU 219 34.124 18.379 4.,396 00 00 c

ATOM 3427 OE1 GLU 219 35.128 17.829 3.956 00 0.00 o

ATOM 3428 OE2 GLU 219 34.090 19.682 4.,787 00 0.00 o

ATOM 3429 H GLU 219 31.584 14.926 4.,675 00 00

ATOM 3430 HA GLU 219 30.128 17.290 3.,919 00 00

ATOM 3431 1HB GLU 219 32.850 16.364 2.,834 00 00 Ή.

ATOM 3432 2HB GLU 219 32.150 17.940 2.,537 00 00 H

ATOM 3433 1HG GLU 219 32.091 18.391 5, .063 00 00

ATOM 3434 2HG GLU 219 32.948 16.874 5..319 00 00

ATOM 3435 N ALA 220 30.333 15.341 1..198 00 00

ATOM 3436 CA ALA 220 29.548 15.014 -0..028 00 00 c

ATOM 3437 C ALA 220 28.045 14.580 0.,162 00 00 G

ATOM 3438 0 ALA 220 27.222 14.892 -0..700 00 00 o

ATOM 3439 CB ALA 220 30.373 13.963 -0.793 00 00 G

ATOM 3440 H ALA 220 31.019 14.707 1.616 00 00 H

ATOM 3441 HA ALA 220 29.515 15.922 -0.663 00 00 H

ATOM 3442 2HB ALA 220 31.396 14.321 -1.019 1.00 00 H ATOM 3443 3HB ALA 220 30.465 13.015 -0.230 1.00 0.00 H

ATOM 3444 1HB ALA 220 29. 903 13. 718 -1. 764 1. 00 0. 00 H

ATOM 3445 N ASP 221 27. 673 13. 910 1. 273 0. 00 0. 00 N

ATOM 3446 CA ASP 221 26. 239 13. 688 1. 644 0. 00 0. 00 C

ATOM 3447 C ASP 221 25. 465 14. 993 2. 065 0. 00 0. 00 C

ATOM 3448 O ASP 221 24. 376 15. 230 1. 549 0. 00 0. 00 O

ATOM 3449 CB ASP 221 26. 204 12. ,559 2. ,708 0. 00 0. ,00 C

ATOM 3450 CG ASP 221 24. 819 11. ,969 2. .965 0. 00 0. ,00 C

ATOM 3451 OD1 ASP 221 24. 367 11. ,006 2. ,358 0. 00 0. ,00 O

ATOM 3452 OD2 ASP 221 24. 139 12. ,629 3. 939 0. 00 0. ,00 O

ATOM 3453 H ASP 221 28. 418 13. .822 1. ,970 0. ,00 0. .00 H

ATOM 3454 HA ASP 221 25. 718 13. ,294 0. ,747 0. .00 0. .00 H

ATOM 3455 1HB ASP 221 26. 623 12. ,912 3. ,668 0. .00 0. ,00 H

ATOM 3456 2HB ASP 221 26. 846 11. ,714 2. ,401 0. .00 0. ,00 H

ATOM 3457 N GLN 222 26. ,020 15, ,846 2, ,948 0. ,00 0. ,00 N

ATOM 3458 CA GLN 222 25. ,508 17, ,230 3, .194 0. .00 0. .00 C

ATOM 3459 C GLN 222 25. ,378 18, .165 1. .936 0. ,00 0. .00 c

ATOM 3460 O GLN 222 24. .335 18. ,799 1. .778 0. ,00 0. .00 o

ATOM 3461 CB GLN 222 26. ,386 17, .811 4, ,342 0. ,00 0. .00 c

ATOM 3462 CG GLN 222 26. .032 19, .239 4, .843 0, .00 0. .00 c

ATOM 3463 CD GLN 222 24. .653 19, .473 5, .471 0, .00 0. .00 c

ATOM 3464 OE1 GLN 222 24, ,006 18. .596 6, ,026 0. .00 0, .00 o

ATOM 3465 NE2 GLN 222 24. .181 20. .690 5, ,436 0, .00 0, .00 N

ATOM 3466 H GLN 222 26. ,927 15. .513 3, .308 0. .00 0, .00 H

ATOM 3467 HA GLN 222 24. ,476 17, .133 3, .581 0. .00 0, .00 H

ATOM 3468 1HB GLN 222 27. ,443 17, .820 4, .007 0, .00 0, .00 H

ATOM 3469 2HB GLN 222 26, ,386 17, .123 5, .211 0. .00 0, .00 H

ATOM 3470 1HG GLN 222 26, .164 19 .937 3, .998 0, .00 0 .00 H

ATOM 3471 2HG GLN 222 26, .782 19 .548 5 .592 0, .00 0 .00 H

ATOM 3472 1HE2 GLN 222 24, .791 21, .403 5, .031 0, .00 0, .00 H

ATOM 3473 2HE2 GLN 222 23, .335 20, .832 5, .994 0. .00 0, .00 H

ATOM 3474 N LEU 223 26, .372 18 .229 1 .029 0, .00 0 .00 N

ATOM 3475 CA LEU 223 26, .196 18 .855 -0 .320 0, .00 0 .00 C

ATOM 3476 C LEU 223 25, .077 18 .220 -1, .228 0, .00 0 .00 C

ATOM 3477 O LEU 223 24, .273 18 .964 -1 .790 0, .00 0 .00 O

ATOM 3478 CB LEU 223 27, .574 18 .890 -1, .036 0, .00 0 .00 C

ATOM 3479 CG LEU 223 28 .621 19 .892 -0 .484 0 .00 0 .00 C

ATOM 3480 CD1 LEU 223 30 .024 19 .505 -0 .967 0, .00 0 .00 C

ATOM 3481 CD2 LEU 223 28 .323 21 .340 -0 .910 0, .00 0 .00 C

ATOM 3482 H LEU 223 27 .209 17 .682 1 .277 0, .00 0 .00 H

ATOM 3483 HA LEU 223 25 .875 19 .903 -0 .167 0 .00 0 .00 H

ATOM 3484 1HB LEU 223 27 .431 19 .098 -2 .114 0 .00 0 .00 H

ATOM 3485 2HB LEU 223 27 .991 17 .864 -1 .018 0 .00 0 .00 H

ATOM 3486 HG LEU 223 28 .625 19 .836 0 .624 0 .00 0 .00 H

ATOM 3487 1HD1 LEU 223 30 .798 20 .200 -0 .594 0 .00 0 .00 H

ATOM 3488 2HD1 LEU 223 30 .316 18 .501 -0 .605 0 .00 0 .00 H

ATOM 3489 3HD1 LEU 223 30 .098 19 .493 -2 .070 0 .00 0 .00 H

ATOM 3490 1HD2 LEU 223 29 .078 22 .043 -0 .512 0 .00 0 .00 H

ATOM 3491 2HD2 LEU 223 28 .321 21 .457 -2 .010 0 .00 0 .00 H

ATOM 3492 3HD2 LEU 223 27 .340 21 .687 -0 .542 0 .00 0 .00 H

ATOM 3493 N GLY 224 24 .971 16 .879 -1 .325 0 .00 0 .00 N

ATOM 3494 CA GLY 224 23 .761 16 .196 -1 .882 0 .00 0 .00 C

ATOM 3495 C GLY 224 22 .365 16 .541 -1 .294 0 .00 0 .00 C

ATOM 3496 O GLY 224 21 .442 16 .813 -2 .062 0 .00 0 .00 O

ATOM 3497 H GLY 224 25 .686 16 .369 -0 .785 0 .00 0 .00 H

ATOM 3498 1HA GLY 224 23 .891 15 .103 -1 .780 0 .00 0 .00 H

ATOM 3499 2HA GLY 224 23 .717 16 .373 -2 .973 0 .00 0 .00 H

ATOM 3500 N LYS 225 22 .214 16 .567 0 .041 0 .00 0 .00 N

ATOM 3501 CA LYS 225 21 .014 17 .158 0 .721 0 .00 0 .00 C

ATOM 3502 C LYS 225 20 .706 18 .667 0 .388 0 .00 0 .00 C

ATOM 3503 O LYS 225 19 .546 19 .021 0 .167 0 .00 0 .00 O

ATOM 3504 CB LYS 225 21 .131 16 .957 2 .265 0 .00 0 .00 C

ATOM 3505 CG LYS 225 21 .189 15 .512 2 .824 0 .00 0 .00 C

ATOM 3506 CD LYS 225 19 .901 14 .685 2 .633 0 .00 0 .00 C

ATOM 3507 CE LYS 225 20 .037 13 .272 3 .223 0 .00 0 .00 C ATOM 3508 NZ LYS 225 18.815 12.492 942 0.00 00 N

ATOM 3509 H LYS 225 23.054 16.261 554 0.00 00 H

ATOM 3510 HA LYS 225 20.125 16.602 359 0.00 00 H

ATOM 3511 1HB LYS 225 20.296 17.489 760 0.00 00 H

ATOM 3512 2HB LYS 225 22.037 17.496 609 ,00 00 H

ATOM 3513 1HG LYS 225 21.454 15.563 899 00 00 H

ATOM 3514 2HG LYS 225 22.050 14.979 367 ,00 00 H

ATOM 3515 1HD LYS 225 19.684 14.633 544 ,00 0.00 H

ATOM 3516 2HD LYS 225 19.048 15.232 081 ,00 0.00 H

ATOM 3517 1HE LYS 225 20.268 13.329 314 ,00 00 H

ATOM 3518 2HE LYS 225 20.950 12.779 797 ,00 00 H

ATOM 3519 1HZ LYS 225 18.869 11.525 284 ,00 00 H

ATOM 3520 2HZ LYS 225 17.965 12.925 318 ,00 00 H

ATOM 3521 3HZ LYS 225 18.666 12.424 923 .00 00 H

ATOM 3522 N ILE 226 21.732 19.536 316 ,00 00 N

ATOM 3523 CA ILE 226 21.621 20.931 0.226 .00 0.00 C

ATOM 3524 C ILE 226 21.094 21.002 1.715 .00 0.00 C

ATOM 3525 O ILE 226 20.117 21.709 1.985 0.00 00 0

ATOM 3526 CB ILE 226 22.974 21.694 077 0.00 00 c

ATOM 3527 CG2 ILE 226 23.097 23.042 680 00 00 c

ATOM 3528 CGI ILE 226 23.199 21.920 609 00 00 c

ATOM 3529 CD1 ILE 226 24.588 22.425 049 00 00 c

ATOM 3530 H ILE 226 22.645 19.102 507 00 00 H

ATOM 3531 HA ILE 226 20.840 21.451 354 00 00 H

ATOM 3532 HB ILE 226 23.802 21.057 291 00 00 H

ATOM 3533 1HG2 ILE 226 24.012 23.602 422 00 00 H

ATOM 3534 2HG2 ILE 226 23.134 22.892 775 00 00 H

ATOM 3535 3HG2 ILE 226 22.233 23.699 476 00 00 H

ATOM 3536 1HG1 ILE 226 23.023 20.969 147 00 0.00 H

ATOM 3537 2HG1 ILE 226 22.414 22.587 008 00 0.00 H

ATOM 3538 1HD1 ILE 226 24.678 22.451 150 00 0.00 H

ATOM 3539 2HD1 ILE 226 25.397 21.772 671 00 0.00 H

ATOM 3540 3HD1 ILE 226 24.791 23.452 699 00 0.00 H

ATOM 3541 N PHE 227 21.731 20.269 655 00 00 N

ATOM 3542 CA PHE 227 21.315 20.204 097 00 00 c

ATOM 3543 C PHE 227 19.856 19.682 362 00 00 c

ATOM 3544 O PHE 227 19.237 20.118 335 00 00 0

ATOM 3545 CB PHE 227 22.453 19.573 952 1.00 00 c

ATOM 3546 CG PHE 227 23.861 20.233 890 .00 00 c

ATOM 3547 CD1 PHE 227 25.001 19.422 872 .00 00 c

ATOM 3548 CE1 PHE 227 26.268 19.986 725 .00 00 c

ATOM 3549 CZ PHE 227 26.409 21.364 606 .00 00 c

ATOM 3550 CE2 PHE 227 25.287 22.183 648 .00 00 c

ATOM 3551 CD2 PHE 227 24.023 21.622 792 1.00 00 c

ATOM 3552 H PHE 227 22.520 19.714 291 1.00 00 H

ATOM 3553 HA PHE 227 21.237 21.254 4.439 1.00 00 H

ATOM 3554 1HB PHE 227 22.523 18.505 4.666 1.00 00 H

ATOM 3555 2HB PHE 227 22.134 19.555 011 1.00 00 H

ATOM 3556 HD1 PHE 227 24.905 18.347 921 1.00 00 H

ATOM 3557 HE1 PHE 227 27.142 19.355 675 1.00 00 H

ATOM 3558 HZ PHE 227 27.391 21.795 475 00 00 H

ATOM 3559 HE2 PHE 227 25.386 23.251 551 00 00 H

ATOM 3560 HD2 PHE 227 23.169 22.277 769 00 00 H

ATOM 3561 N ASP 228 19.319 18.749 546 00 00 N

ATOM 3562 CA ASP 228 17.875 18.360 616 00 00 C

ATOM 3563 C ASP 228 16.823 19.506 356 00 00 C

ATOM 3564 O ASP 228 15.688 19.385 819 00 00 0

ATOM 3565 CB ASP 228 17.638 17.194 615 00 00 C

ATOM 3566 CG ASP 228 18.353 15.875 908 00 00 C

ATOM 3567 OD1 ASP 228 18.420 15.354 015 00 00 0

ATOM 3568 OD2 ASP 228 18.894 15.324 789 00 00 0

ATOM 3569 H ASP 228 19.941 18.383 813 0.00 00 H

ATOM 3570 HA ASP 228 17.670 17.978 635 0.00 00 H

ATOM 3571 1HB ASP 228 16.563 16.946 579 0.00 00 H

ATOM 3572 2HB ASP 228 17.892 17.521 589 0.00 00 H ATOM 3573 N LEU 229 17.160 20.569 -2.601 1.00 0.00 N

ATOM 3574 CA LEU 229 16. 214 21. 670 -2. 250 1. 00 0. 00 C

ATOM 3575 C LEU 229 16. 411 22. 944 -3. 138 1. 00 0. 00 C

ATOM 3576 0 LEU 229 15. 506 23. 312 -3. 891 1. 00 0. 00 O

ATOM 3577 CB LEU 229 16. 347 21. 890 -0. 713 1. 00 0. 00 C

ATOM 3578 CG LEU 229 15. 207 22. 681 -0. 022 1. 00 0. 00 C

ATOM 3579 CD1 LEU 229 15. 231 22. 427 1. 492 1. 00 0. 00 c

ATOM 3580 CD2 LEU 229 15. 248 24. 203 -0. 259 1. ,00 0. ,00 c

ATOM 3581 H LEU 229 18. 142 20. 542 -2. 298 1. ,00 0. ,00 H

ATOM 3582 HA LEU 229 15. 173 21. 337 -2. 436 1. 00 0. ,00 H

ATOM 3583 1HB LEU 229 16. 404 20. 894 -0. 228 1. 00 0. ,00 H

ATOM 3584 2HB LEU 229 17. 323 22. 360 -0. 488 1. 00 0. ,00 H

ATOM 3585 HG LEU 229 14. ,243 22. ,294 -0. ,404 1. ,00 0. .00 H

ATOM 3586 2HD1 LEU 229 15. ,165 21. ,350 1. ,735 1. ,00 0. .00 H

ATOM 3587 3HD1 LEU 229 16. ,154 22. ,812 1. ,964 1. ,00 0. .00 H

ATOM 3588 1HD1 LEU 229 14. ,380 22. ,920 1. 994 1. ,00 0. .00 H

ATOM 3589 2HD2 LEU 229 16. 213 24. ,649 0. 050 1. ,00 0. ,00 H

ATOM 3590 3HD2 LEU 229 15, ,097 24, .466 -1. ,322 1, ,00 0. ,00 H

ATOM 3591 1HD2 LEU 229 14, ,452 24, .734 0. ,296 1. .00 0, .00 H

ATOM 3592 N ILE 230 17, ,564 23, .632 -3. ,036 0. .00 0, ,00 N

ATOM 3593 CA ILE 230 17. ,871 24. .850 -3. ,858 0. ,00 0. ,00 C

ATOM 3594 C ILE 230 18, ,258 24, .567 -5. .357 0, ,00 0, .00 C

ATOM 3595 0 ILE 230 17, ,851 25, .321 -6. .245 0, ,00 0. .00 0

ATOM 3596 CB ILE 230 18, ,896 25, .763 -3. ,081 0, .00 0, .00 c

ATOM 3597 CG2 ILE 230 20. ,345 25. .212 -3, .032 0, ,00 0, .00 c

ATOM 3598 CGI ILE 230 18, ,984 27, .223 -3. .608 0. ,00 0. .00 c

ATOM 3599 GDI ILE 230 17, .734 28 .081 -3, .362 0, .00 0, .00 c

ATOM 3600 H ILE 230 18, .259 23 .185 -2, .427 0, .00 0, .00 H

ATOM 3601 HA ILE 230 16, .932 25. .434 -3, .924 0, .00 0, .00 H

ATOM 3602 HB ILE 230 18, .546 25, .835 -2, .030 0, .00 0, .00 H

ATOM 3603 1HG2 ILE 230 20, .996 25, .826 -2, ,386 0. .00 0, .00 H

ATOM 3604 2HG2 ILE 230 20 .382 24 .183 -2, .632 0, .00 0 .00 H

ATOM 3605 3HG2 ILE 230 20 .818 25 .184 -4, .033 0, .00 0 .00 H

ATOM 3606 1HG1 ILE 230 19 .235 27 .232 -4, .687 0, .00 0, .00 H

ATOM 3607 2HG1 ILE 230 19 .826 27 .751 -3. .117 0, .00 0, .00 H

ATOM 3608 1HD1 ILE 230 17 .909 29 .136 -3. .647 0, .00 0, .00 H

ATOM 3609 2HD1 ILE 230 16 .861 27 .732 -3 .943 0 .00 0 .00 H

ATOM 3610 3HD1 ILE 230 17 .446 28 .093 -2 .293 0, .00 0 .00 H

ATOM 3611 N GLY 231 19 .064 23 .526 -5 .627 0, .00 0 .00 N

ATOM 3612 CA GLY 231 19 .506 23 .170 -7 .000 0 .00 0 .00 C

ATOM 3613 C GLY 231 21 .030 23 .004 -7 .182 0 .00 0 .00 C

ATOM 3614 0 GLY 231 21 .841 23 .491 -6 .389 0 .00 0 .00 O

ATOM 3615 H GLY 231 19 .238 22 .935 - .805 0 .00 0 .00 H

ATOM 3616 1HA GLY 231 19 .153 23 .902 -7 .752 0. .00 0 .00 H

ATOM 3617 2HA GLY 231 19 .008 22 .219 -7 .261 0. .00 0 .00 H

ATOM 3618 N LEU 232 21 .424 22 .342 -8 .282 0 .00 0 .00 N

ATOM 3619 CA LEU 232 22 .839 22 .351 -8 .752 0 .00 0 .00 C

ATOM 3620 C LEU 232 23 .110 23 .743 -9 .452 0 .00 0 .00 C

ATOM 3621 0 LEU 232 22 .432 24 .044 -10 .444 0 .00 0 .00 O

ATOM 3622 CB LEU 232 23 .067 21 .096 -9 .636 0 .00 0 .00 C

ATOM 3623 CG LEU 232 24 .537 20 .683 -9 .901 0 .00 0 .00 C

ATOM 3624 GDI LEU 232 25 .259 20 .180 -8 .636 0 .00 0 .00 C

ATOM 3625 CD2 LEU 232 24 .565 19 .549 -10 .941 0 .00 0 .00 C

ATOM 3626 H LEU 232 20 .644 22 .049 -8 .871 0 .00 0 .00 H

ATOM 3627 HA LEU 232 23 .478 22 .234 -7 .857 0 .00 0 .00 H

ATOM 3628 1HB LEU 232 22 .533 21 .240 -10 .592 0 .00 0 .00 H

ATOM 3629 2HB LEU 232 22 .569 20 .226 -9 .161 0 .00 0 .00 H

ATOM 3630 HG LEU 232 25 .095 21 .556 -10 .287 0 .00 0 .00 H

ATOM 3631 1HD1 LEU 232 26 .300 19 .865 -8 .843 0 .00 0 .00 H

ATOM 3632 2HD1 LEU 232 25 .319 20 .942 -7 .839 0 .00 0 .00 H

ATOM 3633 3HD1 LEU 232 24 .747 19 .305 -8 .188 0 .00 0 .00 H

ATOM 3634 1HD2 LEU 232 25 .592 19 .186 -11 .136 0 .00 0 .00 H

ATOM 3635 2HD2 LEU 232 23 .998 18 .661 -10 .592 0 .00 0 .00 H

ATOM 3636 3HD2 LEU 232 24 .135 19 .849 -11 .912 0 .00 0 .00 H

ATOM 3637 N PRO 233 24 .031 24 .625 -8 .970 0 .00 0 .00 N ATOM 3638 CA PRO 233 24.214 25.988 -9.540 0.00 0.00 C

ATOM 3639 CD PRO 233 24. 993 24. 302 -7. 902 0. 00 0. 00 c

ATOM 3640 C PRO 233 24. 862 26. 148 -10. 967 0. 00 0. 00 c

ATOM 3641 O PRO 233 25. 747 25. 370 -11. 333 0. 00 0. 00 0

ATOM 3642 CB PRO 233 25. 061 26. 638 -8. 429 0. 00 0. 00 c

ATOM 3643 CG PRO 233 25. 944 25. 487 -7. 961 0. 00 0. 00 c

ATOM 3644 HA PRO 233 23. 224 26. 482 -9. 543 0. 00 0. 00 H

ATOM 3645 1HD PRO 233 25. 529 23. 349 -8. 067 0. 00 0. 00 H

ATOM 3646 2HD PRO 233 24. 484 24. 247 -6. ,917 0. 00 0. ,00 H

ATOM 3647 1HB PRO 233 24. 419 27. 002 -7. ,602 0. 00 0. ,00 H

ATOM 3648 2HB PRO 233 25. 647 27. 514 -8. ,772 0. 00 0. ,00 H

ATOM 3649 1HG PRO 233 26. 447 25. ,664 -7. ,002 0. 00 0, .00 H

ATOM 3650 2HG PRO 233 26. 736 25. ,330 -8. ,714 0. 00 0, ,00 H

ATOM 3651 N PRO 234 24. 543 27. ,211 -11, ,767 1. 00 0, ,00 N

ATOM 3652 CA PRO 234 25. 128 27. ,384 -13. ,128 1. 00 0. ,00 C

ATOM 3653 C PRO 234 26. 671 27. ,644 -13. ,176 1. 00 0. ,00 C

ATOM 3654 O PRO 234 27. 289 28. ,081 -12. ,203 1. 00 0, .00 O

ATOM 3655 CB PRO 234 24. 262 28. ,536 -13. ,684 1. ,00 0, .00 C

ATOM 3656 CG PRO 234 23. ,817 29. ,334 -12. ,456 1. ,00 0, .00 C

ATOM 3657 CD PRO 234 23. ,591 28, ,269 -11. ,383 1. ,00 0, .00 C

ATOM 3658 HA PRO 234 24. ,924 26, .474 -13. .720 1. ,00 0, .00 H

ATOM 3659 1HB PRO 234 24, ,804 29, .181 -14, .405 1. ,00 0, .00 H

ATOM 3660 2HB PRO 234 23, .378 28. .140 -14, .217 1. .00 0, .00 H

ATOM 3661 1HG PRO 234 24, ,632 30, .022 -12, .135 1, .00 0 .00 H

ATOM 3662 2HG PRO 234 22. ,928 29. .965 -12, .636 1. ,00 0, .00 H

ATOM 3663 1HD PRO 234 23. ,800 28. ,696 -10, .380 1, ,00 0, .00 H

ATOM 3664 2HD PRO 234 22, ,548 27, .899 -11, .393 1, ,00 0, .00 H

ATOM 3665 N GLU 235 27, .291 27, .381 -14, .349 1, .00 0 .00 N

ATOM 3666 CA GLU 235 28, ,785 27, .413 -14 .518 1. .00 0 .00 C

ATOM 3667 C GLU 235 29, ,567 28, .674 -13 .998 1, .00 0 .00 C

ATOM 3668 O GLU 235 30, .721 28, .534 -13 .590 1, .00 0 .00 O

ATOM 3669 CB GLU 235 29, .183 26, .829 -15 .896 1, .00 0 .00 C

ATOM 3670 CG GLU 235 28, .881 27 .672 -17 .162 1, .00 0 .00 C

ATOM 3671 CD GLU 235 29, ,015 26, .907 -18, .482 1, .00 0 .00 C

ATOM 3672 OE1 GLU 235 28, ,156 26, .911 -19 .356 1, .00 0 .00 O

ATOM 3673 OE2 GLU 235 30, .182 26. .214 -18 .581 1, .00 0 .00 O

ATOM 3674 H GLU 235 26, .677 27 .192 -15 .144 1, .00 0 .00 H

ATOM 3675 HA GLU 235 29, .144 26 .637 -13 .814 1, .00 0 .00 H

ATOM 3676 1HB GLU 235 30 .269 26 .607 -15 .889 1 .00 0 .00 H

ATOM 3677 2HB GLU 235 28 .715 25 .833 -16 .012 1 .00 0 .00 H

ATOM 3678 1HG GLU 235 27 .860 28 .087 -17 .141 1 .00 0 .00 H

ATOM 3679 2HG GLU 235 29 .551 28 .545 -17 .227 1 .00 0 .00 H

ATOM 3680 N ASP 236 28 .976 29 .883 -14 .042 1 .00 0 .00 N

ATOM 3681 CA ASP 236 29 .588 31 .076 -13 .371 1, .00 0 .00 C

ATOM 3682 C ASP 236 29 .545 31 .148 -11 .792 1, .00 0 .00 C

ATOM 3683 O ASP 236 30 .187 32 .030 -11 .222 1 .00 0 .00 O

ATOM 3684 CB ASP 236 28 .994 32 .345 -14 .053 1, .00 0 .00 C

ATOM 3685 CG ASP 236 27 .554 32 .798 -13 .761 1 .00 0 .00 C

ATOM 3686 OD1 ASP 236 27 .145 33 .925 -14 .015 1 .00 0 .00 O

ATOM 3687 OD2 ASP 236 26 .770 31 .834 -13 .205 1 .00 0 .00 O

ATOM 3688 H ASP 236 27 .970 29 .883 -14 .248 1 .00 0 .00 H

ATOM 3689 HA ASP 236 30 .665 31 .091 -13 .622 1 .00 0 .00 H

ATOM 3690 1HB ASP 236 29 .633 33 .204 -13 .784 1 .00 0 .00 H

ATOM 3691 2HB ASP 236 29 .092 32 .270 -15 .150 1 .00 0 .00 H

ATOM 3692 N ASP 237 28 .800 30 .271 -11 .093 0 .00 0 .00 N

ATOM 3693 CA ASP 237 28 .672 30 .263 -9 .602 0 .00 0 .00 C

ATOM 3694 C ASP 237 29 .519 29 .191 -8 .824 0 .00 0 .00 C

ATOM 3695 O ASP 237 29 .722 29 .375 -7 .621 0 .00 0 .00 O

ATOM 3696 CB ASP 237 27 .159 30 .116 -9 .268 0 .00 0 .00 C

ATOM 3697 CG ASP 237 26 .292 31 .356 -9 .486 0 .00 0 .00 C

ATOM 3698 OD1 ASP 237 26 .717 32 .506 -9 .520 0 .00 0 .00 O

ATOM 3699 OD2 ASP 237 24 .973 31 .048 -9 .599 0 .00 0 .00 O

ATOM 3700 H ASP 237 28 .152 29 .740 -11 .690 0 .00 0 .00 H

ATOM 3701 HA ASP 237 29 .007 31 .237 -9 .193 0 .00 0 .00 H

ATOM 3702 1HB ASP 237 27 .027 29 .850 -8 .205 0 .00 0 .00 H ATOM 3703 2HB ASP 237 26.718 29.274 -9.832 0.00 00 H

ATOM 3704 N TRP 238 29.974 28.074 -9.433 0.00 00 N

ATOM 3705 CA TRP 238 30.803 27.045 -8.734 0.00 .00 c

ATOM 3706 C TRP 238 32.264 27.569 -8.425 0.00 ,00 c

ATOM 3707 O TRP 238 32.884 28.102 -9.354 00 ,00 O

ATOM 3708 CB TRP 238 30.796 25.746 -9.594 00 ,00 c

ATOM 3709 CG TRP 238 31.241 24.474 -8.843 00 ,00 c

ATOM 3710 CD1 TRP 238 32.574 24.062 -8.604 00 ,00 c

ATOM 3711 NE1 TRP 238 32.626 22.877 -7.839 00 .00 N

ATOM 3712 CE2 TRP 238 31.301 22.562 -7.614 00 0.00 c

ATOM 3713 CD2 TRP 238 30.450 23.514 -8.229 00 0.00 c

ATOM 3714 CE3 TRP 238 29.044 23.365 -8.153 00 00 c

ATOM 3715 CZ3 TRP 238 28.520 22.279 -7.449 00 00 c

ATOM 3716 CH2 TRP 238 29.361 21.345 -6.834 00 00 c

ATOM 3717 CZ2 TRP 238 30.749 21.466 -6.910 00 00 c

ATOM 3718 H TRP 238 29.749 28.070 -10.434 00 0.00 H

ATOM 3719 HA TRP 238 30.293 26.806 -7.786 0.00 0.00 H

ATOM 3720 1HB TRP 238 31.426 25.890 ■10.492 0.00 0.00 H

ATOM 3721 2HB TRP 238 29.780 25.570 -9.997 00 00 H

ATOM 3722 HD1 TRP 238 33.447 24.614 -8.925 00 00 H

ATOM 3723 HE1 TRP 238 33.449 22.376 -7.473 00 00 H

ATOM 3724 HE3 TRP 238 28.400 24.072 -8.643 00 00 H

ATOM 3725 HZ3 TRP 238 27.451 22.154 -7.371 00 00 H

ATOM 3726 HH2 TRP 238 28.932 20.512 -6.295 00 00 H

ATOM 3727 HZ2 TRP 238 31.390 20.731 -6.447 00 00 H

ATOM 3728 N PRO 239 32.875 27.426 -7.206 00 00 N

ATOM 3729 CA PRO 239 34.246 27.940 -6.936 00 0,00 c

ATOM 3730 CD PRO 239 32.250 26.793 -6.028 00 0.00 c

ATOM 3731 C PRO 239 35.390 27.239 -7.742 00 00 c

ATOM 3732 O PRO 239 35.412 26.019 -7.931 00 00 0

ATOM 3733 CB PRO 239 34.371 27.753 410 00 00 c

ATOM 3734 CG PRO 239 33.429 26.595 076 00 00 c

ATOM 3735 HA PRO 239 34.260 29.027 154 00 00 H

ATOM 3736 1HD PRO 239 31.759 25.827 -6.255 00 00 H

ATOM 3737 2HD PRO 239 31.496 27.470 -5.582 00 00 H

ATOM 3738 1HB PRO 239 34.037 28.671 .887 00 ,00 H

ATOM 3739 2HB PRO 239 35.408 27.566 .069 00 ,00 H

ATOM 3740 1HG PRO 239 33.125 26.576 .013 00 ,00 H

ATOM 3741 2HG PRO 239 33.927 25.628 .289 00 ,00 H

ATOM 3742 N ARG 240 36.358 28.038 -8.206 00 ,00 N

ATOM 3743 CA ARG 240 37.528 27.528 -8.971 00 .00 c

ATOM 3744 C ARG 240 38.605 26.863 -8.041 0.00 .00 c

ATOM 3745 O ARG 240 38.816 27.269 894 0.00 .00 o

ATOM 3746 CB ARG 240 38.103 28.700 824 00 ,00 c

ATOM 3747 CG ARG 240 37.416 28.980 -11.189 00 .00 c

ATOM 3748 CD ARG 240 35.972 29.509 -11.126 00 .00 c

ATOM 3749 NE ARG 240 35.498 29.744 -12.515 00 ,00 N

ATOM 3750 CZ ARG 240 34.296 29.443 -12.994 00 ,00 c

ATOM 3751 NH1 ARG 240 33.336 28.888 -12.316 00 ,00 N

ATOM 3752 NH2 ARG 240 34.067 29.721 -14.228 00 0.00 N

ATOM 3753 H ARG 240 36.291 29.010 -7.897 00 0.00 H

ATOM 3754 HA ARG 240 37.178 26.741 -9.672 00 00 H

ATOM 3755 1HB ARG 240 39.166 28.468 -10.048 00 00 H

ATOM 3756 2HB ARG 240 38.180 29.625 -9.218 00 00 H

ATOM 3757 1HG ARG 240 37.456 28.054 -11.798 00 00 H

ATOM 3758 2HG ARG 240 38.055 29.703 -11.736 00 00 H

ATOM 3759 1HD ARG 240 35.926 30.448 -10.536 00 00 H

ATOM 3760 2HD ARG 240 35.338 28.783 -10.575 00 00 H

ATOM 3761 HE ARG 240 36.114 30.178 -13.208 00 00 H

ATOM 3762 1HH1 ARG 240 32.422 28.764 -12.777 00 00 H

ATOM 3763 2HH1 ARG 240 33.516 28.730 -11.318 00 0.00 H

ATOM 3764 1HH2 ARG 240 33.124 29.494 -14.560 00 0.00 H

ATOM 3765 2HH2 ARG 240 34.812 30.168 -14.761 00 0.00 H

ATOM 3766 N ASP 241 39.292 25.825 -8.556 00 0.00 N

ATOM 3767 CA ASP 241 40.358 25.071 -7.808 00 0.00 C ATOM 3768 C ASP 241 39.923 24.,188 -6.,568 0.00 0.00 C

ATOM 3769 O ASP 241 40. 787 23. ,732 -5. ,814 0. 00 0. 00 0

ATOM 3770 CB ASP 241 41. 607 25. ,968 -7. ,527 0. 00 0. 00 c

ATOM 3771 CG ASP 241 42. 292 26. ,565 -8. .757 0. ,00 0. 00 c

ATOM 3772 OD1 ASP 241 42. 733 25. ,897 -9, .685 0. ,00 0. .00 0

ATOM 3773 OD2 ASP 241 42. ,352 27. ,923 -8, .714 0. ,00 0. ,00 0

ATOM 3774 H ASP 241 39. ,139 25. ,653 -9, ,551 0. ,00 0. ,00 H

ATOM 3775 HA ASP 241 40. ,718 24. .305 -8, ,521 0. ,00 0. ,00 H

ATOM 3776 1HB ASP 241 42. ,382 25, .377 -7, ,009 0. .00 0. .00 H

ATOM 3777 2HB ASP 241 41. ,349 26. .776 -6, .819 0. .00 0. .00 H

ATOM 3778 N VAL 242 38. .627 23. ,864 -6, .385 0. .00 0. .00 N

ATOM 3779 CA VAL 242 38. .160 22. .882 -5, .352 0, .00 0, .00 C

ATOM 3780 C VAL 242 38, .301 21. .394 -5, .828 0. .00 0. .00 C

ATOM 3781 O VAL 242 38, .058 21, .066 -6, .994 0, .00 0. .00 O

ATOM 3782 CB VAL 242 36. ,701 23, .176 -4, ,847 0. .00 0. ,00 C

ATOM 3783 CGI VAL 242 36, ,576 24. .519 -4, .103 0. .00 0, .00 C

ATOM 3784 CG2 VAL 242 35. .586 23. .090 -5, .915 0. .00 0, .00 C

ATOM 3785 H VAL 242 37, .996 24. .327 -7. .044 0. .00 0, .00 H

ATOM 3786 HA VAL 242 38, .814 22. ,999 -4, .462 0. .00 0, .00 H

ATOM 3787 HB VAL 242 36, .468 22. ,401 -4, .087 0, ,00 0. .00 H

ATOM 3788 1HG1 VAL 242 35, .578 24. .648 -3, .645 0, ,00 0. ,00 H

ATOM 3789 2HG1 VAL 242 37, ,315 24, .590 -3, .282 0, ,00 0. .00 H

ATOM 3790 3HG1 VAL 242 36, .748 25, .381 -4, .775 0. ,00 0. .00 H

ATOM 3791 1HG2 VAL 242 34, .579 23, .207 -5, .473 0. .00 0. ,00 H

ATOM 3792 2HG2 VAL 242 35. .697 23, .867 -6, .692 0, .00 0, .00 H

ATOM 3793 3HG2 VAL 242 35. .590 22, .114 -6, .436 0. .00 0. ,00 H

ATOM 3794 N SER 243 38, .628 20, .471 -4. .907 1, .00 0. ,00 N

ATOM 3795 CA SER 243 38, .721 19, .011 -5 .232 1. .00 0, .00 C

ATOM 3796 C SER 243 37, .400 18, .213 -5 .553 1, .00 0, .00 C

ATOM 3797 O SER 243 37, .498 17, .073 -6 .016 1. .00 0, .00 O

ATOM 3798 CB SER 243 39, .504 18, .346 -4 .076 1, .00 0, .00 C

ATOM 3799 OG SER 243 39, .836 16, .993 -4 .398 1, .00 0, .00 O

ATOM 3800 H SER 243 38, .858 20, .855 -3 .985 1, .00 0, .00 H

ATOM 3801 HA SER 243 39, .349 18 .908 -6 .140 1, .00 0, .00 H

ATOM 3802 1HB SER 243 40. .443 18 .896 -3. .863 1, .00 0, .00 H

ATOM 3803 2HB SER 243 38 .918 18 .375 -3 .135 1, .00 0, .00 H

ATOM 3804 HG SER 243 39 .061 16 .610 -4 .833 1, .00 0 .00 H

ATOM 3805 N LEU 244 36 .199 18 .765 -5 .307 0, .00 0, .00 N

ATOM 3806 CA LEU 244 34 .897 18 .139 -5 .677 0, .00 0 .00 C

ATOM 3807 C LEU 244 34 .244 18 .920 -6 .883 0, .00 0 .00 C

ATOM 3808 O LEU 244 33 .808 20 .058 -6 .668 0 .00 0 .00 O

ATOM 3809 CB LEU 244 33 .969 18 .138 -4 .425 0 .00 0 .00 C

ATOM 3810 CG LEU 244 34 .270 17 .109 -3 .304 0 .00 0 .00 C

ATOM 3811 GDI LEU 244 33 .468 17 .453 -2 .036 0 .00 0 .00 C

ATOM 3812 CD2 LEU 244 33 .925 15 .671 -3 .729 0 .00 0 .00 C

ATOM 3813 H LEU 244 36 .266 19 .738 -4 .991 0 .00 0 .00 H

ATOM 3814 HA LEU 244 35 .038 17 .084 -5 .967 0 .00 0 .00 H

ATOM 3815 1HB LEU 244 32 .919 18 .000 -4 .746 0 .00 0 .00 H

ATOM 3816 2HB LEU 244 33 .982 19 .157 -3 .993 0 .00 0 .00 H

ATOM 3817 HG LEU 244 35 .348 17 .160 -3 .048 0 .00 0 .00 H

ATOM 3818 1HD1 LEU 244 33 .677 16 .749 -1 .209 0 .00 0 .00 H

ATOM 3819 2HD1 LEU 244 33 .723 18 .458 -1 .649 0 .00 0 .00 H

ATOM 3820 3HD1 LEU 244 32 .375 17 .441 -2 .207 0 .00 0 .00 H

ATOM 3821 1HD2 LEU 244 34 .119 14 .949 -2 .913 0 .00 0 .00 H

ATOM 3822 2HD2 LEU 244 32 .860 15 .563 -4 .012 0 .00 0 .00 H

ATOM 3823 3HD2 LEU 244 34 .531 15 .337 -4 .589 0 .00 0 .00 H

ATOM 3824 N PRO 245 34 .147 18 .393 -8 .141 0 .00 0 .00 N

ATOM 3825 CA PRO 245 33 .520 19 .134 -9 .277 0 .00 0 .00 C

ATOM 3826 CD PRO 245 34 .784 17 .120 -8 .544 0 .00 0 .00 C

ATOM 3827 C PRO 245 31 .954 19 .034 -9 .362 0 .00 0 .00 C

ATOM 3828 O PRO 245 31 .323 18 .194 -8 .715 0 .00 0 .00 O

ATOM 3829 CB PRO 245 34 .249 18 .473 -10 .467 0, .00 0 .00 C

ATOM 3830 CG PRO 245 34 .478 17 .021 -10, .038 0, .00 0, ,00 C

ATOM 3831 HA PRO 245 33 .796 20, .207 -9, .229 0, .00 0, .00 H

ATOM 3832 1HD PRO 245 34 .377 16, .251 -7, .992 0, ,00 0, ,00 H ATOM 3833 2HD PRO 245 35.,878 17.,156 -8,,362 0.,00 0.00 H

ATOM 3834 1HB PRO 245 35. ,225 18. ,975 -10. .630 0. ,00 0. 00 H

ATOM 3835 2HB PRO 245 33. ,699 18. ,552 -11, .424 0. .00 0. 00 H

ATOM 3836 1HG PRO 245 35. ,292 16, ,529 -10, .604 0. ,00 0. 00 H

ATOM 3837 2HG PRO 245 33. ,560 16, ,423 -10, .198 0. .00 0. .00 H

ATOM 3838 N ARG 246 31. ,330 19, .890 -10, .190 1. ,00 0. .00 N

ATOM 3839 CA ARG 246 29. .850 19, .875 -10, .418 1. .00 0. .00 C

ATOM 3840 C ARG 246 29. .252 18, .513 -10, .943 1. .00 0. ,00 C

ATOM 3841 O ARG 246 28. .328 17, .977 -10, .327 1. .00 0. ,00 O

ATOM 3842 CB ARG 246 29, .530 21. ,091 -11, .336 1. .00 0. .00 C

ATOM 3843 CG ARG 246 28, .021 21, .376 -11, .523 1. .00 0. .00 C

ATOM 3844 CD ARG 246 27, .728 22, .382 -12, .645 1. .00 0, .00 C

ATOM 3845 NE ARG 246 26, .255 22, .521 -12, .723 1. .00 0, .00 N

ATOM 3846 CZ ARG 246 25, .575 23, .153 -13, .668 1. .00 0, .00 C

ATOM 3847 NH1 ARG 246 26, .110 23, .681 -14, .728 1. .00 0, .00 N

ATOM 3848 NH2 ARG 246 24, .303 23, .256 -13, .512 1. .00 0, .00 N

ATOM 3849 H ARG 246 31, .943 20, .635 -10, .535 1. .00 0. .00 H

ATOM 3850 HA ARG 246 29, .365 20, .058 -9, .438 1. .00 0. .00 H

ATOM 3851 1HB ARG 246 30, .005 22, .006 -10, .924 1. .00 0. .00 H

ATOM 3852 2HB ARG 246 30, .012 20, .936 -12, .322 1. .00 0, .00 H

ATOM 3853 1HG ARG 246 27 .491 20 .426 -11 .740 1. .00 0, .00 H

ATOM 3854 2HG ARG 246 27 .605 21 .729 -10 .556 1, .00 0, .00 H

ATOM 3855 1HD ARG 246 28 .205 23, .362 -12 .418 1, .00 0, .00 H

ATOM 3856 2HD ARG 246 28 .165 22, .026 -13 .602 1, .00 0, .00 H

ATOM 3857 HE ARG 246 25 .673 22, .216 -11, .938 1, .00 0, .00 H

ATOM 3858 2HH1 ARG 246 27 .132 23. .629 -14. .746 1, .00 0, .00 H

ATOM 3859 IHHl ARG 246 25, .528 24, .195 -15 .391 1, .00 0, .00 H

ATOM 3860 1HH2 ARG 246 23. .974 23, .023 -1 .571 1, .00 0, .00 H

ATOM 3861 2HH2 ARG 246 23 .838 23, .887 -14, .164 1, .00 0, .00 H

ATOM 3862 N GLY 247 29 .853 17, .983 -12. .042 1, .00 0, .00 N

ATOM 3863 CA GLY 247 29 .574 16, .625 -12, .615 1, .00 0. ,00 C

ATOM 3864 C GLY 247 29, .463 15, .401 -11, .680 1, .00 0, ,00 C

ATOM 3865 O GLY 247 28 .738 14 .462 -12 .010 1, .00 0, .00 O

ATOM 3866 H GLY 247 30 .655 18 .547 -12 .344 1, .00 0, .00 H

ATOM 3867 1HA GLY 247 28 .631 16 .674 -13 .192 1, .00 0, .00 H

ATOM 3868 2HA GLY 247 30 .347 16, .382 -13 .366 1, .00 0, .00 H

ATOM 3869 N ALA 248 30 .235 15, .362 -10 .581 0, .00 0, .00 N

ATOM 3870 CA ALA 248 30 .054 14 .291 -9. .558 0, .00 0, .00 C

ATOM 3871 C ALA 248 28 .648 14 .187 -8 .851 0, .00 0, .00 C

ATOM 3872 O ALA 248 28 .341 13 .141 -8 .273 0, .00 0, .00 O

ATOM 3873 CB ALA 248 31 .163 14, .550 -8 .520 0, .00 0, .00 C

ATOM 3874 H ALA 248 30 .673 16, .260 -10 .347 0, .00 0, .00 H

ATOM 3875 HA ALA 248 30 .239 13, .306 -10 .029 0, .00 0, .00 H

ATOM 3876 1HB ALA 248 31 .161 13, .776 -7 .730 0, .00 0, .00 H

ATOM 3877 2HB ALA 248 32 .173 14 .537 -8 .969 0 .00 0 .00 H

ATOM 3878 3HB ALA 248 31 .040 15 .526 -8 .008 0 .00 0 .00 H

ATOM 3879 N PHE 249 27 .820 15 .249 -8 .858 0 .00 0 .00 N

ATOM 3880 CA PHE 249 26 .554 15 .315 -8 .083 0 .00 0 .00 C

ATOM 3881 C PHE 249 25 .303 15 .106 -9 .020 0 .00 0 .00 C

ATOM 3882 O PHE 249 24 .964 16 .043 -9 .747 0 .00 0 .00 O

ATOM 3883 CB PHE 249 26 .510 16 .684 -7 .339 0, .00 0 .00 C

ATOM 3884 CG PHE 249 27 .522 16, .868 -6 .193 0, .00 0, .00 C

ATOM 3885 GDI PHE 249 28 .747 17. .499 -6, .427 0, .00 0, .00 c

ATOM 3886 CE1 PHE 249 29 .662 17, .676 -5, .392 0, .00 0, .00 c

ATOM 3887 CZ PHE 249 29 .352 17, .221 -4, .109 0, .00 0, .00 c

ATOM 3888 CE2 PHE 249 28 .137 16, .590 -3, .867 0, .00 0, ,00 c

ATOM 3889 CD2 PHE 249 27 .221 16 .412 -4, .901 0 .00 0 .00 C

ATOM 3890 H PHE 249 28 .179 16 .057 -9 .382 0. .00 0 .00 H

ATOM 3891 HA PHE 249 26 .545 14, .543 -7. .291 0, .00 0, .00 H

ATOM 3892 1HB PHE 249 25 .493 16, .839 -6, .930 0, .00 0, .00 H

ATOM 3893 2HB PHE 249 26 .614 17, .507 -8, .073 0, .00 0, ,00 H

ATOM 3894 HD1 PHE 249 28 .997 17, .852 -7, .418 0, .00 0, ,00 H

ATOM 3895 HE1 PHE 249 30 .606 18, .165 -5, .586 0, .00 0, ,00 H

ATOM 3896 HZ PHE 249 30, .060 17, ,354 -3, .303 0, .00 0, ,00 H

ATOM 3897 HE2 PHE 249 27, .898 16, ,237 -2. .873 0, ,00 0. .00 H ATOM 3898 HD2 PHE 249 26.279 15..927 -4.,693 0.00 0.00 H

ATOM 3899 N PRO 250 24. 526 13. 981 -8. 990 0. 00 0. 00 N

ATOM 3900 CA PRO 250 23. 325 13. 823 -9. .869 0. 00 0. 00 C

ATOM 3901 CD PRO 250 24. 930 12. 730 -8. .314 0. 00 0. ,00 C

ATOM 3902 C PRO 250 22. 008 14. ,681 -9. ,649 0. 00 0. ,00 C

ATOM 3903 O PRO 250 21. 325 14. ,848 -10. ,666 0. ,00 0. ,00 O

ATOM 3904 CB PRO 250 23. ,096 12. ,298 -9, ,833 0. .00 0. ,00 C

ATOM 3905 CG PRO 250 23. ,739 11. .800 -8. ,538 0, .00 0. ,00 C

ATOM 3906 HA PRO 250 23. 640 14. ,074 -10. ,902 0. .00 0. ,00 H

ATOM 3907 1HD PRO 250 25. 125 12. ,864 -7. ,232 0. ,00 0. ,00 H

ATOM 3908 2HD PRO 250 25. ,852 12. ,320 -8, ,772 0. ,00 0. ,00 H

ATOM 3909 1HB PRO 250 22. ,029 12. .012 -9, ,908 0, .00 0. .00 H

ATOM 3910 2HB PRO 250 23. ,600 11. .828 -10. ,700 0, .00 0, .00 H

ATOM 3911 1HG PRO 250 23. .024 11. .886 -7. .697 0. .00 0. .00 H

ATOM 3912 2HG PRO 250 24. ,041 10. .737 -8. ,590 0. ,00 0. .00 H

ATOM 3913 N PRO 251 21. ,547 15. .211 -8, ,467 0, ,00 0. .00 N

ATOM 3914 CA PRO 251 20. ,245 15. .940 -8, ,368 0, .00 0. .00 C

ATOM 3915 CD PRO 251 22, .202 15. ,017 -7. .160 0, .00 0, .00 C

ATOM 3916 C PRO 251 20. .263 17, .458 -8, .773 0, .00 0. .00 C

ATOM 3917 O PRO 251 21, ,274 18, .153 -8, .642 0, .00 0, .00 O

ATOM 3918 CB PRO 251 19, .914 15, .726 -6, .876 0, .00 0, .00 C

ATOM 3919 CG PRO 251 21, ,270 15. .715 -6, .168 0, .00 0. .00 C

ATOM 3920 HA PRO 251 19, ,480 15, .416 -8, .972 0, .00 0, .00 H

ATOM 3921 1HD PRO 251 23, .210 15, .470 -7, .121 0, .00 0, .00 H

ATOM 3922 2HD PRO 251 22, .297 13, .943 -6, .914 0, .00 0, .00 H

ATOM 3923 1HB PRO 251 19, .237 16, .489 -6, .441 0, .00 0, .00 H

ATOM 3924 2HB PRO 251 19. .408 14 .754 -6 .716 0, .00 0, .00 H

ATOM 3925 1HG PRO 251 21, .605 16 .753 -5 .985 0 .00 0 .00 H

ATOM 3926 2HG PRO 251 21, .222 15. .219 -5, .178 0, .00 0, .00 H

ATOM 3927 N ARG 252 19, .097 17, .978 -9, .203 0, .00 0, .00 N

ATOM 3928 CA ARG 252 18, .893 19, .454 -9, .378 0, .00 0, .00 C

ATOM 3929 C ARG 252 17, .425 19 .908 -9, .093 0, .00 0, .00 C

ATOM 3930 O ARG 252 17, .222 20 .774 -8. .244 0 .00 0, .00 O

ATOM 3931 CB ARG 252 19, .485 20 .037 -10 .695 0 .00 0 .00 C

ATOM 3932 CG ARG 252 18. .993 19 .463 -12 .044 0 .00 0 .00 C

ATOM 3933 CD ARG 252 19, .698 20, .127 -13, .236 0 .00 0, .00 C

ATOM 3934 NE ARG 252 19, .273 19 .432 -14, .475 0 .00 0, .00 N

ATOM 3935 CZ ARG 252 19, .786 19 .615 -15, .685 0 .00 0, .00 C

ATOM 3936 NH1 ARG 252 20, .744 20 .456 -15. .956 0 .00 0, .00 N

ATOM 3937 NH2 ARG 252 19, .299 18 .917 -16 .649 0 .00 0 .00 N

ATOM 3938 H ARG 252 18 .323 17 .332 -9 .033 0 .00 0 .00 H

ATOM 3939 HA ARG 252 19. .460 19 .948 -8, .558 0 .00 0. .00 H

ATOM 3940 1HB ARG 252 19, .351 21 .137 -10 .678 0 .00 0, .00 H

ATOM 3941 2HB ARG 252 20, .581 19 .890 -10 .632 0 .00 0, .00 H

ATOM 3942 1HG ARG 252 19 .178 18 .368 -12 .041 0 .00 0 .00 H

ATOM 3943 2HG ARG 252 17 .897 19 .592 -12 .130 0 .00 0 .00 H

ATOM 3944 1HD ARG 252 19 .451 21 .210 -13 .271 0 .00 0 .00 H

ATOM 3945 2HD ARG 252 20 .799 20 .055 -13 .093 0 .00 0 .00 H

ATOM 3946 HE ARG 252 18, .542 18 .714 -14 .441 1 .00 0, .00 H

ATOM 3947 IHHl ARG 252 21, .067 20 .536 -16 .922 0 .00 0 .00 H

ATOM 3948 2HH1 ARG 252 21 .069 20 .984 -15 .144 0 .00 0 .00 H

ATOM 3949 1HH2 ARG 252 18 .560 18 .254 -16 .412 0 .00 0 .00 H

ATOM 3950 2HH2 ARG 252 19 .703 19 .057 -17 .578 0 .00 0 .00 H

ATOM 3951 N GLY 253 16 .417 19 .338 -9 .787 0 .00 0 .00 N

ATOM 3952 CA GLY 253 14 .974 19 .531 -9 .455 0 .00 0 .00 C

ATOM 3953 C GLY 253 14, .400 20 .969 -9 .319 0 .00 0 .00 C

ATOM 3954 0 GLY 253 14, .015 21 .304 -8 .192 0 .00 0 .00 O

ATOM 3955 H GLY 253 16, .755 18 .597 -10 .406 0 .00 0 .00 H

ATOM 3956 1HA GLY 253 14, .353 18 .996 -10 .193 0 .00 0 .00 H

ATOM 3957 2HA GLY 253 14 .772 19 .013 -8 .497 0 .00 0 .00 H

ATOM 3958 N PRO 254 14. .235 21 .824 -10 .377 0 .00 0 .00 N

ATOM 3959 CA PRO 254 13 .590 23 .164 -10 .230 0 .00 0 .00 C

ATOM 3960 CD PRO 254 14, .784 21 .570 -11, .726 0, .00 0, .00 C

ATOM 3961 C PRO 254 12, .024 23 .098 -10, .101 0, .00 0, .00 C

ATOM 3962 O PRO 254 11, .263 23 .362 -11, .036 0 .00 0, .00 O ATOM 3963 CB PRO 254 14.137 23.888 -11.481 0.00 0.00 c

ATOM 3964 CG PRO 254 14. 334 22. 792 -12. 528 0. 00 0. 00 c

ATOM 3965 HA PRO 254 13. 981 23. .690 -9. 334 0. 00 0. 00 H

ATOM 3966 1HD PRO 254 14. 406 20. ,629 -12. 169 0. 00 0. 00 H

ATOM 3967 2HD PRO 254 15. 890 21. ,515 -11. 684 0. 00 0. 00 H

ATOM 3968 1HB PRO 254 13. 472 24. .702 -11. 831 0. 00 0. 00 H

ATOM 3969 2HB PRO 254 15. 106 24. ,368 -11. ,238 0. 00 0. 00 H

ATOM 3970 1HG PRO 254 13. .367 22. ,585 -13. ,030 0. 00 0. 00 H

ATOM 3971 2HG PRO 254 15. 053 23. ,082 -13. ,316 0. 00 0. .00 H

ATOM 3972 N ARG 255 11. .559 22. ,697 -8. ,909 0. 00 0. ,00 N

ATOM 3973 CA ARG 255 10. ,148 22, ,287 -8. ,659 0. 00 0. ,00 C

ATOM 3974 C ARG 255 9. ,772 22, ,433 -7. ,130 0. 00 0. .00 C

ATOM 3975 O ARG 255 10. ,606 22, .082 -6. ,286 0. 00 0. .00 0

ATOM 3976 CB ARG 255 9. ,894 20, .838 -9, ,185 0. 00 0. ,00 c

ATOM 3977 CG ARG 255 10, ,692 19, .686 -8. .520 0. .00 0. .00 c

ATOM 3978 CD ARG 255 10, ,367 18, .315 -9, .128 0. ,00 0. ,00 c

ATOM 3979 NE ARG 255 11, ,155 17, .265 -8, .431 0. ,00 0, ,00 N

ATOM 3980 CZ ARG 255 10, .925 15, .961 -8, .493 0. ,00 0. ,00 C

ATOM 3981 NH1 ARG 255 9, .966 15, .416 -9, .178 0, ,00 0. .00 N

ATOM 3982 NH2 ARG 255 11, .713 15, .185 -7, .831 0. .00 0, ,00 N

ATOM 3983 H ARG 255 12, .310 22 .485 -8, .236 0. .00 0, ,00 H

ATOM 3984 HA ARG 255 9, .497 22 .974 -9. .233 0, .00 0, .00 H

ATOM 3985 1HB ARG 255 8, .809 20 .634 -9, .092 0, .00 0, .00 H

ATOM 3986 2HB ARG 255 10 .081 20 .839 -10 .277 0. .00 0. .00 H

ATOM 3987 1HG ARG 255 11 .774 19 .904 -8 .618 0, .00 0. .00 H

ATOM 3988 2HG ARG 255 10 .514 19 .703 -7 .429 0, .00 0, .00 H

ATOM 3989 1HD ARG 255 9 .274 18 .139 -9 .033 0, .00 0, .00 H

ATOM 3990 2HD ARG 255 10 .591 18 .323 -10 .216 0, .00 0, .00 H

ATOM 3991 HE ARG 255 11 .926 17 .532 -7 .807 1, .00 0, .00 H

ATOM 3992 IHHl ARG 255 9 .864 14 .400 -9 .154 0, .00 0, .00 H

ATOM 3993 2HH1 ARG 255 9 .374 16 .087 -9 .672 0, .00 0, .00 H

ATOM 3994 1HH2 ARG 255 12 .450 15 .639 -7 .285 0, ,00 0, .00 H

ATOM 3995 2HH2 ARG 255 11 .534 14 .181 -7 .868 0, .00 0, .00 H

ATOM 3995 N PRO 256 8 .547 22 .861 -6 .694 0, .00 0, .00 N

ATOM 3997 CA PRO 256 8 .161 22 .860 -5 .246 0, .00 0, .00 C

ATOM 3998 CD PRO 256 7 .537 23 .468 -7 .578 0, .00 0. .00 C

ATOM 3999 C PRO 256 7 .779 21 .448 -4 .666 0, .00 0. .00 C

ATOM 4000 O PRO 256 6 .625 21 .164 -4 .325 0, .00 0. .00 O

ATOM 4001 CB PRO 256 7 .038 23 .921 -5. .255 0, .00 0, .00 C

ATOM 4002 CG PRO 256 6 .388 23 .816 -6 .637 0, .00 0 .00 C

ATOM 4003 HA PRO 256 8 .989 23 .253 -4 .621 0, .00 0. .00 H

ATOM 4004 1HD PRO 256 7 .204 22 .785 -8 .384 0, .00 0. .00 H

ATOM 4005 2HD PRO 256 7 .934 24 .388 -8 .053 0, .00 0. .00 H

ATOM 4006 1HB PRO 256 6 .309 23 .796 -4 .431 0, .00 0, .00 H

ATOM 4007 2HB PRO 256 7 .474 24 .931 -5 .121 0, .00 0, .00 H

ATOM 4008 1HG PRO 256 5 .633 23 .006 -6 .635 0, .00 0, .00 H

ATOM 4009 2HG PRO 256 5 .861 24 .745 -6 .929 0, .00 0. .00 H

ATOM 4010 N VAL 257 8 .753 20 .524 -4 .562 0 .00 0. .00 N

ATOM 4011 CA VAL 257 8 .509 19 .071 -4 .233 0, .00 0 .00 C

ATOM 4012 C VAL 257 8 .546 18 .734 -2 .696 0. .00 0 .00 C

ATOM 4013 O VAL 257 9 .251 19 .388 -1 .922 0 .00 0 .00 O

ATOM 4014 CB VAL 257 9 .454 18 .171 -5 .106 0 .00 0 .00 c

ATOM 4015 CGI VAL 257 10 .966 18 .301 -4 .798 0 .00 0 .00 c

ATOM 4016 CG2 VAL 257 9 .094 16 .668 -5 .090 0 .00 0 .00 c

ATOM 4017 H VAL 257 9 .667 20 .884 -4 .869 0 .00 0 .00 H

ATOM 4018 HA VAL 257 7 .479 18 .835 -4 .571 0 .00 0 .00 H

ATOM 4019 HB VAL 257 9 .293 18 .494 -6 .150 0 .00 0 .00 H

ATOM 4020 1HG1 VAL 257 11 .208 17 .970 -3 .769 0 .00 0 .00 H

ATOM 4021 2HG1 VAL 257 11 .600 17 .713 -5 .482 0 .00 0 .00 H

ATOM 4022 3HG1 VAL 257 11 .314 19 .350 -4 .871 0 .00 0 .00 H

ATOM 4023 1HG2 VAL 257 8 .027 16 .498 -5 .326 0 .00 0 .00 H

ATOM 4024 2HG2 VAL 257 9 .680 16 .091 -5 .825 0 .00 0 .00 H

ATOM 4025 3HG2 VAL 257 9 .286 16 .206 -4 .101 0 .00 0 .00 H

ATOM 4026 N GLN 258 7 .754 17 .717 -2 .267 0 .00 0 .00 N

ATOM 4027 CA GLN 258 7 .394 17 .427 -0 .836 0 .00 0 .00 C ATOM 4028 C GLN 258 ,842 18.742 0.156 0.00 0.00 c

ATOM 4029 O GLN 258 ,901 18.176 0.416 0.00 0.00 0

ATOM 4030 CB GLN 258 ,546 16..712 0.056 0.00 0.00 c

ATOM 4031 CG GLN 258 .675 17..569 0.603 0.00 0.00 c

ATOM 4032 CD GLN 258 11.106 17..275 0.144 0.00 0.00 c

ATOM 4033 OE1 GLN 258 11.763 16..343 0.594 0.00 0.00 0

ATOM 4034 NE2 GLN 258 11.635 18..064 ,752 0.00 0.00 N

ATOM 4035 H GLN 258 7.214 17..296 .026 0.00 00 H

ATOM 4036 HA GLN 258 6.604 16..648 ,946 ,00 00 H

ATOM 4037 1HB GLN 258 8.060 16..146 ,762 00 00 H

ATOM 4038 2HB GLN 258 8.979 15..914 .690 ,00 00 H

ATOM 4039 1HG GLN 258 9.469 18..653 .518 ,00 0.00 H

ATOM 4040 2HG GLN 258 9.657 17..402 .695 0.00 0.00 H

ATOM 4041 1HE2 GLN 258 10.995 18..758 .160 0.00 00 H

ATOM 4042 2HE2 GLN 258 12.582 17..812 .048 00 00 H

ATOM 4043 N SER 259 6.274 19..742 .469 00 00 N

ATOM 4044 CA SER 259 6.876 21..109 .325 00 00 c

ATOM 4045 C SER 259 8.201 21..440 .130 00 00 c

ATOM 4046 O SER 259 8.506 20..777 ,127 00 00 0

ATOM 4047 CB SER 259 .768 21..674 .118 00 00 c

ATOM 4048 OG SER 259 .537 21..360 ,774 1.00 00 0

ATOM 4049 H SER 259 .418 19..446 .946 00 00 H

ATOM 4050 HA SER 259 .149 21..739 .874 00 00 H

ATOM 4051 1HB SER 259 .885 22..775 1.108 00 00 H

ATOM 4052 2HB SER 259 .611 21..295 1.722 00 00 H

ATOM 4053 HG SER 259 .707 21..364 .727 00 00 H

ATOM 4054 N VAL 260 8.942 22..511 .779 00 00 N

ATOM 4055 CA VAL 260 10.212 22..891 .489 00 00 c

ATOM 4056 C VAL 260 10.023 23..460 .947 00 0.00 c

ATOM 4057 O VAL 260 10.614 22..946 .907 00 0.00 0

ATOM 4058 CB VAL 260 11.177 23..734 .569 00 0.00 c

ATOM 4059 CGI VAL 260 11.552 23..034 .760 00 0.00 c

ATOM 4060 CG2 VAL 260 10.708 25..159 0.207 00 0.00 c

ATOM 4061 H VAL 260 8.621 22.999 0.061 00 0.00 H

ATOM 4062 HA VAL 260 10.769 21.948 .658 00 0.00 H

ATOM 4063 HB VAL 260 12.123 23.851 .137 00 0.00 H

ATOM 4064 1HG1 VAL 260 12.355 23.571 .302 00 00 H

ATOM 4065 2HG1 VAL 260 11.914 22.003 .595 00 00 H

ATOM 4066 3HG1 VAL 260 10.694 22.961 .455 00 0.00 H

ATOM 4067 1HG2 VAL 260 11.469 25.711 .378 00 0.00 H

ATOM 4068 2HG2 VAL 260 9.779 25.161 .393 00 00 H

ATOM 4069 3HG2 VAL 260 10.515 25.778 .101 0.00 00 H

ATOM 4070 N VAL 261 9.171 24.486 .129 0.00 00 N

ATOM 4071 CA VAL 261 8.772 25.008 .474 00 00 c

ATOM 4072 C VAL 261 7.200 25.124 .596 00 00 c

ATOM 4073 O VAL 261 6.644 26.211 .367 00 00 0

ATOM 4074 CB VAL 261 9.527 26.328 .868 00 00 c

ATOM 4075 CGI VAL 261 10.973 26.057 .327 00 0.00 c

ATOM 4076 CG2 VAL 261 9.557 27.447 .797 0.00 0.00 c

ATOM 4077 H VAL 261 8.742 24.846 .271 0.00 00 H

ATOM 4078 HA VAL 261 9.051 24.282 .260 00 00 H

ATOM 4079 HB VAL 261 8.997 26.753 .747 00 00 H

ATOM 4080 1HG1 VAL 261 11.465 26.987 .668 00 00 H

ATOM 4081 2HG1 VAL 261 11.012 25.352 6.176 00 00 H

ATOM 4082 3HG1 VAL 261 11.597 25.639 4.514 00 00 H

ATOM 4083 1HG2 VAL 261 9.936 28.402 .202 00 00 H

ATOM 4084 2HG2 VAL 261 10.196 27.190 .934 00 00 H

ATOM 4085 3HG2 VAL 261 8.550 27.659 .394 00 00 H

ATOM 4086 N PRO 262 425 24.061 .972 00 00 N

ATOM 4087 CA PRO 262 960 24.172 .221 00 00 C

ATOM 4088 CD PRO 262 940 22.677 .087 00 00 C

ATOM 4089 C PRO 262 613 24.610 .701 00 0.00 C

ATOM 4090 O PRO 262 999 23.930 .652 00 0.00 O

ATOM 4091 CB PRO 262 521 22.735 .870 00 00 C

ATOM 4092 CG PRO 262 683 21.832 .305 00 00 C ATOM 4093 HA PRO 262 4.484 24.848 4.489 0.00 0.00 H

ATOM 4094 1HD PRO 262 7. 647 22. 568 5. 930 0. 00 0. ,00 H

ATOM 4095 2HD PRO 262 7. ,455 22. ,368 4. 157 0. 00 0. ,00 H

ATOM 4096 1HB PRO 262 4. 353 22. 660 3. 777 0. 00 0. 00 H

ATOM 4097 2HB PRO 262 3. ,553 22. ,467 5. ,338 0. ,00 0, ,00 H

ATOM 4098 1HG PRO 262 5, ,704 20. .879 4. .746 0. ,00 0. ,00 H

ATOM 4099 2HG PRO 262 5. .572 21. .585 6. 378 0. ,00 0. ,00 H

ATOM 4100 N GLU 263 3, ,916 25. ,685 7. ,084 1. ,00 0. .00 N

ATOM 4101 CA GLU 263 3, ,265 26. .686 6. .192 1, .00 0. ,00 C

ATOM 4102 C GLU 263 3, ,866 28. ,108 6. ,441 1. ,00 0, .00 C

ATOM 4103 O GLU 263 3, ,524 28. .792 7. ,412 1. .00 0, .00 O

ATOM 4104 CB GLU 263 1. ,726 26. ,658 6. ,437 1. .00 0, ,00 C

ATOM 4105 CG GLU 263 0, ,965 25. ,357 6. ,054 1, .00 0, .00 C

ATOM 4106 CD GLU 263 0, ,998 24, ,932 4, ,584 1, .00 0. .00 C

ATOM 4107 OE1 GLU 263 1, ,429 25. ,616 3. ,661 1, .00 0. .00 O

ATOM 4108 OE2 GLU 263 0, ,494 23, .683 4. .409 1. ,00 0, ,00 O

ATOM 4109 H GLU 263 3, .813 25, ,732 8. .100 1, ,00 0, .00 H

ATOM 4110 HA GLU 263 3. .399 26, ,452 5. ,122 1, .00 0, ,00 H

ATOM 4111 1HB GLU 263 1, ,515 26, ,907 7, ,495 1, .00 0, .00 H

ATOM 4112 2HB GLU 263 1, .271 27, .490 5, .863 1, .00 0, .00 H

ATOM 4113 1HG GLU 263 1, ,336 24. ,502 6, ,641 1, ,00 0, .00 H

ATOM 4114 2HG GLU 263 -0, .102 25. .454 6. .309 1, ,00 0, .00 H

ATOM 4115 N MET 264 4, .771 28, .550 5, .554 1, .00 0, .00 N

ATOM 4116 CA MET 264 5, .483 29, .855 5. ,684 1. .00 0, .00 C

ATOM 4117 C MET 264 5, .025 30, .894 4, .601 1, .00 0, .00 C

ATOM 4118 O MET 264 4, .839 30, .569 3, ,423 1. .00 0, .00 O

ATOM 4119 CB MET 264 6, .987 29, .489 5, ,647 1. .00 0. .00 C

ATOM 4120 CG MET 264 7, .973 30, .652 5, .842 1, .00 0 .00 G

ATOM 4121 SD MET 264 9, .582 29, .961 6. .258 1, .00 0, .00 s-

ATOM 4122 CE MET 264 10, .611 31, .385 5, .925 1, .00 0, .00 C

ATOM 4123 H MET 264 4 .982 27 .888 4, .799 1, .00 0 .00 H

ATOM 4124 HA MET 264 5, .289 30, .296 6, .684 1, .00 0, .00 H

ATOM 4125 1HB MET 264 7 .189 28 .740 6, .438 1, .00 0, .00 H

ATOM 4126 2HB MET 264 7 .222 28 .979 4 .694 1 .00 0 .00 H

ATOM 4127 1HG MET_ 264 8 .034 31 .277 4, .929 1, .00 0, .00 H

ATOM 4128 2HG MET 264 7 .653 31 .321 6 .663 1, .00 0 .00 H

ATOM 4129 1HE MET 264 10 .681 31 .564 4, .839 1, .00 0 .00 H

ATOM 4130 3HE MET 264 10 .192 32 .291 6, .398 1, .00 0, .00 H

ATOM 4131 2HE MET 264 11 .631 31 .230 6 .317 1. .00 0 .00 H

ATOM 4132 N GLU 265 4 .841 32 .163 5, .008 1, .00 0, .00 N

ATOM 4133 CA GLU 265 4 .334 33 .243 4. .110 1, .00 0 .00 C

ATOM 4134 C GLU 265 5 .344 33 .752 3 .018 1 .00 0 .00 C

ATOM 4135 O GLU 265 6 .559 33 .758 3, .223 1, .00 0 .00 O

ATOM 4136 CB GLU 265 3 .762 3 .389 4 .998 1. .00 0 .00 C

ATOM 4137 CG GLU 265 4 .782 35 .241 5 .807 1 .00 0 .00 C

ATOM 4138 CD GLU 265 4 .153 36 .350 6, .648 1, .00 0 .00 C

ATOM 4139 OE1 GLU 265 3 .361 36 .150 7 .562 1 .00 0 .00 O

ATOM 4140 OE2 GLU 265 4 .584 37 .588 6 .286 1 .00 0 .00 O

ATOM 4141 H GLU 265 5 .004 32 .338 6 .002 1, .00 0 .00 H

ATOM 4142 HA GLU 265 3 .462 32 .823 3. .569 1 .00 0 .00 H

ATOM 4143 1HB GLU 265 3 .178 35 .072 4, .351 1. .00 0 .00 H

ATOM 4144 2HB GLU 265 3 .003 33 .974 5 .693 1, .00 0 .00 H

ATOM 4145 1HG GLU 265 5 .358 34 .612 6 .502 1 .00 0 .00 H

ATOM 4146 2HG GLU 265 5 .523 35 .707 5, .135 1, .00 0, .00 H

ATOM 4147 N GLU 266 4 .821 34 .233 1. .876 0, .00 0 .00 N

ATOM 4148 CA GLU 266 5 .631 34 .645 0 .679 0 .00 0 .00 C

ATOM 4149 C GLU 266 6 .805 35 .651 0, .928 0, .00 0, .00 C

ATOM 4150 O GLU 266 7 .890 35 .455 0 .379 0, .00 0 .00 O

ATOM 4151 CB GLU 266 4 .669 35 .130 -0 .441 0 .00 0 .00 C

ATOM 4152 CG GLU 266 3 .768 34 .034 -1, .073 0, .00 0, .00 C

ATOM 4153 CD GLU 266 2 .845 34 .554 -2 .170 0, .00 0 .00 C

ATOM 4154 OE1 GLU 266 1 .726 35 .009 -1 .963 0 .00 0 .00 O

ATOM 4155 OE2 GLU 266 3 .401 34 .452 -3, .407 0. .00 0. .00 O

ATOM 4156 H GLU 266 3 .800 34 .169 1 .817 0, .00 0, .00 H

ATOM 4157 HA GLU 266 6 .119 33 .728 0 .296 0. .00 0 .00 H ATOM 4158 1HB GLU 266 5.264 35.579 -1.262 0.00 0.00 H

ATOM 4159 2HB GLU 266 4. 041 35. 964 -0. 068 0. 00 0. 00 H

ATOM 4160 1HG GLU 266 3. 116 33. 564 -0. 318 0. 00 0. 00 H

ATOM 4161 2HG GLU 265 4. 372 33. 221 -1. 507 0. 00 0. 00 H

ATOM 4162 N SER 267 6. 604 36. 711 1. 733 1. 00 0. 00 N

ATOM 4163 CA SER 267 7. 697 37. 657 2. 103 1. 00 0. 00 C

ATOM 4164 C SER 267 8. 838 36. 995 2. ,958 1. 00 0. 00 C

ATOM 4165 O SER 267 10. 012 37. 254 2. ,683 1. 00 0. 00 O

ATOM 4166 CB SER 267 7. 081 38. 882 2. 821 1. 00 0. 00 C

ATOM 4167 OG SER 267 6. 176 39. 600 1. ,980 1. 00 0. 00 O

ATOM 4168 H SER 267 5. 650 36. 777 2. ,105 1. 00 0. 00 H

ATOM 4169 HA SER 267 8. 177 38. 020 1. ,172 1. 00 0. .00 H

ATOM 4170 1HB SER 267 6. 551 38. 567 3. ,744 1. .00 0. ,00 H

ATOM 4171 2HB SER 267 7. ,879 39. ,569 3. ,163 1. ,00 0. ,00 H

ATOM 4172 HG SER 267 6. ,660 39. ,888 1, .201 1. ,00 0. ,00 H

ATOM 4173 N GLY 268 8. ,515 36. ,115 3. .926 0. ,00 0. ,00 N

ATOM 4174 CA GLY 268 9. ,521 35. ,220 4. ,570 0. ,00 0. .00 C

ATOM 4175 C GLY 268 10, .215 34, ,159 3. .684 0. ,00 0, .00 C

ATOM 4176 O GLY 268 11, .430 34, .004 3. .780 0, ,00 0. .00 O

ATOM 4177 H GLY 268 7, .508 35, .901 3, .932 0, ,00 0. .00 H

ATOM 4178 1HA GLY 268 9. ,034 34. ,685 5, .407 0. ,00 0. ,00 H

ATOM 4179 2HA GLY 268 10. ,303 35, ,836 5, ,051 0. ,00 0, .00 H

ATOM 4180 N ALA 269 9, .476 33. ,450 2, .818 1, ,00 0, .00 N

ATOM 4181 CA ALA 269 10, .068 32, .579 1, .763 1, ,00 0, .00 C

ATOM 4182 C ALA 269 11, .002 33, .262 0, .694 1. .00 0, .00 C

ATOM 4183 O ALA 269 12, ,034 32. .687 0, .343 1. .00 0, .00 O

ATOM 4184 CB ALA 269 8, .883 31. .832 1, .128 1. .00 0. .00 c

ATOM 4185 H ALA 269 8, .466 33, .666 2, .852 1, .00 0, .00 H

ATOM 4186 HA ALA 269 10, .691 31, .818 2 .269 1, .00 0, .00 H

ATOM 4187 2HB ALA 269 8, .269 31, .297 1 .880 1, .00 0, .00 H

ATOM 4188 3HB ALA 269 8, .202 32, .522 0 .593 1, .00 0, .00 H

ATOM 4189 1HB ALA 269 9, .221 31. .079 0 .394 1, .00 0, .00 H

ATOM 4190 N GLN 270 10, ,690 34, ,486 0, .220 1. .00 0, .00 N

ATOM 4191 CA GLN 270 11, .657 35, .350 -0 .525 1, .00 0, .00 C

ATOM 4192 C GLN 270 12, .987 35, .691 0 .245 1, .00 0, .00 C

ATOM 4193 O GLN 270 14, .070 35, .494 -0 .311 1. .00 0, .00 O

ATOM 4194 CB GLN 270 10 .866 36, .610 -0 .978 1 .00 0 .00 C

ATOM 4195 CG GLN 270 11 .612 37 .549 -1 .965 1 .00 0 .00 C

ATOM 4196 CD GLN 270 10 .862 38 .848 -2 .272 1 .00 0 .00 C

ATOM 4197 OE1 GLN 270 10 .440 39 .587 -1 .391 1 .00 0 .00 O

ATOM 4198 NE2 GLN 270 10 .702 39 .203 -3 .520 1 .00 0 .00 N

ATOM 4199 H GLN 270 9 .770 34 .833 0 .533 1 .00 0 .00 H

ATOM 4200 HA GLN 270 11 .963 34 .801 -1 .438 1 .00 0 .00 H

ATOM 4201 1HB GLN 270 9 .910 36 .302 -1 .450 1 .00 0 .00 H

ATOM 4202 2HB GLN 270 10 .557 37 .183 -0 .080 1 .00 0 .00 H

ATOM 4203 1HG GLN 270 12 .593 37 .844 -1 .545 1 .00 0 .00 H

ATOM 4204 2HG GLN 270 11 .858 36 .998 -2 .892 1 .00 0 .00 H

ATOM 4205 1HE2 GLN 270 11 .096 38 .579 -4 .227 1 .00 0 .00 H

ATOM 4206 2HE2 GLN 270 10 .207 40 .089 -3 .636 1 .00 0 .00 H

ATOM 4207 N LEU 271 12 .915 36 .150 1 .510 0 .00 0 .00 N

ATOM 4208 CA LEU 271 14 .101 36 .231 2 .417 0 .00 0 .00 C

ATOM 4209 C LEU 271 14 .870 34 .880 2 .667 0 .00 0 .00 C

ATOM 4210 O LEU 271 16 .098 34 .866 2 .582 0 .00 0 .00 O

ATOM 4211 CB LEU 271 13 .619 36 .915 3 .730 0 .00 0 .00 C

ATOM 4212 CG LEU 271 14 .691 37 .180 4 .820 0 .00 0 .00 C

ATOM 4213 GDI LEU 271 15 .763 38 .188 4 .373 0 .00 0 .00 C

ATOM 4214 CD2 LEU 271 14 .028 37 .679 6 .111 0 .00 0 .00 C

ATOM 4215 H LEU 271 11 .953 36 .278 1 .848 0 .00 0 .00 H

ATOM 4216 HA LEU 271 14 .829 36 .913 1 .932 0 .00 0 .00 H

ATOM 4217 1HB LEU 271 12 .811 36 .295 4 .167 0 .00 0 .00 H

ATOM 4218 2HB LEU 271 13 .125 37 .872 3 .484 0 .00 0 .00 H

ATOM 4219 HG LEU 271 15 .196 36 .222 5 .057 0 .00 0 .00 H

ATOM 4220 1HD1 LEU 271 16 .504 38 .393 5 .167 0 .00 0 .00 H

ATOM 4221 2HD1 LEU 271 16 .331 37 .821 3 .497 0 .00 0 .00 H

ATOM 4222 3HD1 LEU 271 15 .321 39 .158 4 .082 0 .00 0 .00 H ATOM 4223 1HD2 LEU 271 14.763 37.,795 6.,929 0.00 0.00 H

ATOM 4224 2HD2 LEU 271 13. ,536 38. ,661 5. ,969 0. 00 0. 00 H

ATOM 4225 3HD2 LEU 271 13. ,255 36. ,977 6. ,473 0. 00 0. ,00 H

ATOM 4226 N LEU 272 14. 177 33. ,761 2. ,952 0. 00 0. 00 N

ATOM 4227 CA LEU 272 14. ,799 32. ,408 3. ,071 0. 00 0. 00 C

ATOM 4228 C LEU 272 15. ,620 31. ,907 1, .833 0. 00 0. 00 C

ATOM 4229 O LEU 272 16. ,721 31. ,396 2, .028 0. 00 0. 00 O

ATOM 4230 CB LEU 272 13. ,673 31. ,414 3, .483 0. 00 0. 00 C

ATOM 4231 CG LEU 272 14. ,099 29. .949 3, .775 0. 00 0. .00 C

ATOM 4232 GDI LEU 272 14. ,925 29. .833 5. ,060 0. 00 0. ,00 C

ATOM 4233 CD2 LEU 272 12, ,875 29. .032 3, ,893 0. 00 0. ,00 c

ATOM 4234 H LEU 272 13, .159 33. .914 3. ,017 0. ,00 0. ,00 H

ATOM 4235 HA LEU 272 15, .518 32, .462 3, .910 0. ,00 0. ,00 H

ATOM 4236 1HB LEU 272 12. .920 31, .408 2, .671 0. .00 0, .00 H

ATOM 4237 2HB LEU 272 13. ,128 31. .813 4, .361 0. ,00 0, .00 H

ATOM 4238 HG LEU 272 14. ,709 29. .575 2, .928 0. ,00 0, .00 H

ATOM 4239 1HD1 LEU 272 15. .251 28, .794 5, .242 0. ,00 0. .00 H

ATOM 4240 2HD1 LEU 272 15, .845 30, .443 5, .019 0. ,00 0, .00 H

ATOM 4241 3HD1 LEU 272 14, .352 30, .154 5, .950 0, .00 0, .00 H

ATOM 4242 1HD2 LEU 272 13, .165 27, .977 4, .045 0. .00 0, .00 H

ATOM 4243 2HD2 LEU 272 12, .222 29, .319 4, .738 0, .00 0, .00 H

ATOM 4244 3HD2 LEU 272 12, .254 29, .064 2, .979 0, .00 0, .00 H

ATOM 4245 N LEU 273 15, .124 32, .052 0 .593 0, ,00 0, .00 N

ATOM 4246 CA LEU 273 15, .925 31, .776 -0, .641 0, ,00 0, .00 C

ATOM 4247 C LEU 273 17 .127 32, .756 -0 .911 0, .00 0, .00 C

ATOM 4248 O LEU 273 18 .181 32 .305 -1 .359 0. .00 0 .00 O

ATOM 4249 CB LEU 273 14, .956 31, .713 -1, .854 0, .00 0, .00 c

ATOM 4250 CG LEU 273 13, .869 30, .602 -1, .859 0, .00 0. ,00 c

ATOM 4251 GDI LEU 273 12, .850 30, .885 -2, .972 0, .00 0, ,00 c

ATOM 4252 CD2 LEU 273 14, .458 29, .195 -2, .055 0, .00 0, .00 c

ATOM 4253 H LEU 273 14, .202 32, .509 0, .560 0, .00 0, .00 H

ATOM 4254 HA LEU 273 16, .392 30, .777 -0 .536 0. .00 0, .00 H

ATOM 4255 1HB LEU 273 15, .548 31, .628 -2 .786 0. .00 0, .00 H

ATOM 4256 2HB LEU 273 14 .464 32 .704 -1 .937 0. .00 0, .00 H

ATOM 4257 HG LEU 273 13. .322 30, .627 -0 .894 0. .00 0, .00 H

ATOM 4258 1HD1 LEU 273 12 .039 30 .134 -2 .988 0, .00 0. .00 H

ATOM 4259 2HD1 LEU 273 12 .358 31 .867 -2 .825 0. .00 0 .00 H

ATOM 4260 3HD1 LEU 273 13 .312 30 .898 -3 .976 0, .00 0 .00 H

ATOM 4261 1HD2 LEU 273 13 .670 28 .420 -2 .059 0, .00 0 .00 H

ATOM 4262 2HD2 LEU 273 15 .009 29 .110 -3 .010 0, .00 0 .00 H

ATOM 4263 3HD2 LEU 273 15 .160 28 .929 -1 .243 0, .00 0 .00 H

ATOM 4264 N GLU 274 17 .006 34 .065 -0 .619 1, .00 0 .00 N

ATOM 4265 CA GLU 274 18 .167 35 .010 -0 .562 1, .00 0 .00 C

ATOM 4266 C GLU 274 19 .260 34 .713 0 .542 1, .00 0 .00 C

ATOM 4267 O GLU 274 20 .454 34 .856 0 .271 1. .00 0 .00 O

ATOM 4268 CB GLU 274 17 .583 36 .447 -0 .446 1, .00 0 .00 C

ATOM 4269 CG GLU 274 16 .795 36 .973 -1 .680 1, .00 0 .00 C

ATOM 4270 CD GLU 274 16 .212 38 .382 -1 .553 1 .00 0 .00 C

ATOM 4271 OE1 GLU 274 16 .073 38 .995 -0 .499 1 .00 0 .00 O

ATOM 4272 OE2 GLU 274 15 .846 38 .886 -2 .761 1 .00 0 .00 O

ATOM 4273 H GLU 274 16 .069 34 .361 -0 .312 1, .00 0 .00 H

ATOM 4274 HA GLU 274 18 .700 34 .957 -1 .532 1, .00 0 .00 H

ATOM 4275 1HB GLU 274 16 .949 36 .528 0 .459 1, .00 0 .00 H

ATOM 4276 HB GLU 274 18 .406 37 .162 -0 .271 1, .00 0 .00 H

ATOM 4277 1HG GLU 274 17 .426 36 .967 -2 .583 1, .00 0 .00 H

ATOM 4278 2HG GLU 274 15 .938 36 .319 -1 .908 1, .00 0 .00 H

ATOM 4279 N MET 275 18 .875 34 .283 1 .761 1, .00 0 .00 N

ATOM 4280 CA MET 275 19 .797 33 .613 2 .735 1, .00 0 .00 C

ATOM 4281 C MET 275 20 .391 32 .239 2 .251 1, .00 0 .00 C

ATOM 4282 O MET 275 21 .609 32 .044 2, .286 1, .00 0 .00 O

ATOM 4283 CB MET 275 19 .046 33 .407 4, .082 1, .00 0 .00 C

ATOM 4284 CG MET 275 18 .708 34 .665 4. .899 1, .00 0 .00 C

ATOM 4285 SD MET 275 17 .783 34 .162 6, .358 1. .00 0 .00 s

ATOM 4286 CE MET 275 17 .619 35 .764 7, .142 1, .00 0 .00 c

ATOM 4287 H MET 275 17 .854 34 .323 1, .898 1, .00 0 .00 H ATOM 4288 HA MET 275 20.659 34.282 2.921 1.00 0.00 H

ATOM 4289 1HB MET 275 18. 112 32. 838 3. .902 1. 00 0. 00 H

ATOM 4290 2HB MET 275 19. 651 32. .754 4. ,740 1. ,00 0. 00 H

ATOM 4291 1HG MET 275 19. 626 35. 202 5. ,203 1. 00 0. 00 H

ATOM 4292 2HG MET 275 18. 094 35. ,374 4. ,309 1. ,00 0. 00 H

ATOM 4293 1HE MET 275 18. 613 36. ,206 7. .317 1. ,00 0. ,00 H

ATOM 4294 3HE MET 275 17. 043 36. ,456 6. ,504 1. .00 0. .00 H

ATOM 4295 2HE MET 275 17. 096 35. ,673 8. ,111 1. ,00 0. ,00 H

ATOM 4296 N LEU 276 19. ,547 31. ,292 1, ,798 0. .00 0. ,00 N

ATOM 4297 CA LEU 276 19. 995 30. ,019 1. ,166 0. ,00 0. ,00 C

ATOM 4298 C LEU 276 20. ,310 30. ,194 -0, ,366 0. ,00 0. ,00 C

ATOM 4299 O LEU 276 19. ,618 29, .664 -1. .239 0. ,00 0. ,00 O

ATOM 4300 CB LEU 276 18. ,928 28. ,915 1, .460 0, ,00 0. .00 C

ATOM 4301 CG LEU 276 18. ,674 28. ,517 2, .941 0. ,00 0. .00 C

ATOM 4302 CD1 LEU 276 17, ,521 27. ,507 3, .055 0, .00 0. .00 C

ATOM 4303 CD2 LEU 276 19, .917 27, .920 3, .618 0, .00 0. ,00 C

ATOM 4304 H LEU 276 18, ,553 31. ,570 1. .809 0, .00 0. ,00 H

ATOM 4305 HA LEU 276 20, ,935 29. ,682 1, .640 0. .00 0. .00 H

ATOM 4306 1HB LEU 276 19, ,206 28. .004 0, .897 0, .00 0, .00 H

ATOM 4307 2HB LEU 276 17, .970 29. ,233 1, ,002 0, .00 0. .00 H

ATOM 4308 HG LEU 276 18, .367 29, .427 3, .496 0. .00 0. .00 H

ATOM 4309 1HD1 LEU 276 17, .288 27, .272 4, .111 0, .00 0. .00 H

ATOM 4310 2HD1 LEU 276 16, .590 27, .911 2, .614 0, .00 0, .00 H

ATOM 4311 3HD1 LEU 276 17, .743 26, .554 2, .541 0, .00 0, .00 H

ATOM 4312 1HD2 LEU 276 19, .701 27, .560 4, .640 0, .00 0, .00 H

ATOM 4313 2HD2 LEU 276 20, .325 27 .065 3, .051 0 .00 0, .00 H

ATOM 4314 3HD2 LEU 276 20, ,728 28, ,664 3, .719 0. .00 0. .00 H

ATOM 4315 N THR 277 21, .385 30, .931 -0. .686 0, .00 0, .00 N

ATOM 4316 CA THR 277 21, .895 31, .113 -2 .079 0 .00 0, .00 C

ATOM 4317 C THR 277 23, .322 30 .494 -2, .173 0, .00 0, .00 C

ATOM 4318 O THR 277 24, .177 30, .760 -1, .330 0, .00 0, .00 O

ATOM 4319 CB THR 277 21, .868 32 .634 -2. .427 0, .00 0 .00 C

ATOM 4320 OG1 THR 277 20 .530 33 .117 -2 .424 0 .00 0 .00 O

ATOM 4321 CG2 THR 277 22, .397 33, .019 -3, .816 0, .00 0, .00 c

ATOM 4322 H THR 277 21, .770 31 .431 0, .125 0, .00 0 .00 H

ATOM 4323 HA THR 277 21 .233 30 .604 -2 .809 0 .00 0 .00 H

ATOM 4324 HB THR 277 22, .441 33, .200 -1, .666 0, .00 0, .00 H

ATOM 4325 HG1 THR 277 19 .998 32 .602 -1, .798 0. .00 0 .00 H

ATOM 4326 1HG2 THR 277 22 .247 34 .099 - .004 0 .00 0 .00 H

ATOM 4327 2HG2 THR 277 23 .481 32 .827 -3 .916 0 .00 0 .00 H

ATOM 4328 3HG2 THR 277 21 .872 32 .476 -4 .624 0 .00 0 .00 H

ATOM 4329 N PHE 278 23 .608 29 .657 -3 .186 0 .00 0 .00 N

ATOM 4330 CA PHE 278 24 .945 28 .993 -3 .309 0 .00 0 .00 C

ATOM 4331 C PHE 278 26 .193 29 .953 -3 .356 0 .00 0. .00 C

ATOM 4332 O PHE 278 27 .163 29 .709 -2 .636 0 .00 0 .00 O

ATOM 4333 CB PHE 278 24 .884 27 .976 -4 .488 0 .00 0 .00 C

ATOM 4334 CG PHE 278 26 .171 27 .148 -4 .679 0 .00 0 .00 C

ATOM 4335 CD1 PHE 278 26 .322 25 .888 -4 .091 0 .00 0 .00 C

ATOM 4336 CE1 PHE 278 27 .524 25 .190 -4 .230 0 .00 0 .00 C

ATOM 4337 CZ PHE 278 28 .582 25 .757 -4 .935 0 .00 0 .00 C

ATOM 4338 CE2 PHE 278 28 .443 27 .019 -5 .501 0 .00 0 .00 C

ATOM 4339 CD2 PHE 278 27 .239 27 .701 -5 .394 0 .00 0 .00 C

ATOM 4340 H PHE 278 22 .833 29 .489 -3 .836 0 .00 0 .00 H

ATOM 4341 HA PHE 278 25 .089 28 .387 -2 .391 0 .00 0 .00 H

ATOM 4342 1HB PHE 278 24 .655 28 .512 -5 .431 0 .00 0 .00 H

ATOM 4343 2HB PHE 278 24 .025 27 .291 -4 .350 0 .00 0 .00 H

ATOM 4344 HD1 PHE 278 25 .517 25 .454 -3 .516 0 .00 0 .00 H

ATOM 4345 HE1 PHE 278 27 .642 24 .217 -3 .776 0 .00 0 .00 H

ATOM 4346 HZ PHE 278 29 .515 25 .225 -5 .038 0 .00 0 .00 H

ATOM 4347 HE2 PHE 278 29 .262 27 .488 -6 .017 0 .00 0 .00 H

ATOM 4348 HD2 PHE 278 27 .156 28 .678 -5 .852 0 .00 0 .00 H

ATOM 4349 N ASN 279 26 .208 30 .968 -4, .238 0 .00 0 .00 N

ATOM 4350 CA ASN 279 27 .372 31 .881 -4 .366 0 .00 0 .00 C

ATOM 4351 C ASN 279 27 .398 32. .939 -3, .199 0. .00 0, .00 C

ATOM 4352 O ASN 279 26 .497 33, .785 -3, .196 0, .00 0, .00 O ATOM 4353 CB ASN 279 27.302 32.506 -5.787 0.00 0.00 c

ATOM 4354 CG ASN 279 28.476 33.402 -6.195 0.00 0.00 c

ATOM 4355 OD1 ASN 279 29.402 33.689 .447 0.00 0.00 0

ATOM 4356 ND2 ASN 279 28.475 33.890 .406 0.00 0.00 N

ATOM 4357 H ASN 279 25.328 31.109 -4.744 0.00 00 H

ATOM 4358 HA ASN 279 28.294 31.270 -4.352 00 00 H

ATOM 4359 1HB ASN 279 26.368 33.086 -5.902 00 0.00 H

ATOM 4360 2HB ASN 279 27.235 31.696 -6.541 00 0.00 H

ATOM 4361 1HD2 ASN 279 27.824 33.433 -8.066 00 00 H

ATOM 4362 2HD2 ASN 279 29.350 34.354 -7.659 00 00 H

ATOM 4363 N PRO 280 28.390 32.997 .258 00 00 N

ATOM 4364 CA PRO 280 28.449 34.076 ,224 00 0.00 c

ATOM 4365 CD PRO 280 29.508 32.035 ,166 0.00 0.00 c

ATOM 4366 C PRO 280 28.532 35.568 ,706 0.00 00 c

ATOM 4367 O PRO 280 28.057 36.461 ,006 00 00 0

ATOM 4368 CB PRO 280 29.643 33.624 -0.364 00 00 c

ATOM 4369 CG PRO 280 30.513 32.763 -1.277 00 00 c

ATOM 4370 HA PRO 280 27.541 34.012 597 00 00 H

ATOM 4371 1HD PRO 280 29.974 31.793 141 00 00 H

ATOM 4372 2HD PRO 280 29.178 31.085 -1.698 00 00 H

ATOM 4373 1HB PRO 280 29.288 33.002 0.482 00 00 H

ATOM 4374 2HB PRO 280 30.212 34.461 0.083 00 00 H

ATOM 4375 1HG PRO 280 31.157 32.063 -0.710 00 00 H

ATOM 4376 2HG PRO 280 31.181 33.400 -1.890 00 00 H

ATOM 4377 N HIS 281 29.065 35.822 -2.912 00 00 N

ATOM 4378 CA HIS 281 28.950 37.137 -3.618 00 00 c

ATOM 4379 C HIS 281 27.492 37.567 -4.039 00 00 c

ATOM 4380 O HIS 281 27.160 38.752 -3.981 00 00 0

ATOM 4381 CB HIS 281 29.885 37.105 -4.865 00 00 c

ATOM 4382 CG HIS 281 31.368 36.796 ,628 00 00 c

ATOM 4383 ND1 HIS 281 32.217 37.622 ,910 00 00 N

ATOM 4384 CE1 HIS 281 33.340 36.836 ,910 00 00 c

ATOM 4385 NE2 HIS 281 33.331 35.622 ,542 00 00 N

ATOM 4386 CD2 HIS 281 32.029 35.613 .009 00 00 c

ATOM 4387 H HIS 281 29.411 34.976 .379 00 00 H

ATOM 4388 HA HIS 281 29.321 37.929 .936 00 00 H

ATOM 4389 1HB HIS 281 29.483 36.393 -5.609 00 00 H

ATOM 4390 2HB HIS 281 29.836 38.087 -5.371 00 00 H

ATOM 4391 HE1 HIS 281 34.232 37.184 405 00 00 H

ATOM 4392 HE2 HIS 281 34.068 34.913 619 00 0.00 H

ATOM 4393 HD2 HIS 281 31.578 34.804 565 1.00 0.00 H

ATOM 4394 N LYS 282 26.637 36.621 477 0.00 00 N

ATOM 4395 CA LYS 282 25.166 36.857 653 0.00 00 C

ATOM 4396 C LYS 282 24.260 36.666 372 0.00 00 C

ATOM 4397 O LYS 282 23.113 37.122 376 0.00 00 O

ATOM 4398 CB LYS 282 24.678 35.959 828 00 00 C

ATOM 4399 CG LYS 282 25.192 36.363 233 00 00 C

ATOM 4400 CD LYS 282 24.806 35.355 -8.333 00 00 C

ATOM 4401 CE LYS 282 25.268 35.831 -9.718 00 00 C

ATOM 4402 NZ LYS 282 25.084 34.760 -10.716 00 00 N

ATOM 4403 H LYS 282 27.019 35.674 -4.373 00 00 H

ATOM 4404 HA LYS 282 24.994 37.911 -4.952 00 00 H

ATOM 4405 1HB LYS 282 23.569 35.972 ,854 00 00 H

ATOM 4406 2HB LYS 282 24.929 34.903 .606 00 00 H

ATOM 4407 1HG LYS 282 26.297 36.465 .203 00 00 H

ATOM 4408 2HG LYS 282 24.811 37.375 -7.478 00 00 H

ATOM 4409 1HD LYS 282 23.711 35.181 -8.326 00 0.00 H

ATOM 4410 2HD LYS 282 25.258 34.367 -8.093 00 0.00 H

ATOM 4411 1HE LYS 282 26.345 36.118 -9.679 00 00 H

ATOM 4412 2HE LYS 282 24.729 36.759 -10.015 00 00 H

ATOM 4413 1HZ LYS 282 25.453 34.923 -11.667 00 00 H

ATOM 4414 2HZ LYS 282 25.620 33.899 -10.449 00 00 H

ATOM 4415 3HZ LYS 282 24.135 34.383 -10.814 00 00 H

ATOM 4416 N ARG 283 24.733 36.020 -2.292 00 00 N

ATOM 4417 CA ARG 283 24.021 35.938 -0.989 0.00 00 C ATOM 4418 C ARG 283 23.996 37.309 -0.231 0.00 0.00 c

ATOM 4419 O ARG 283 25. 014 37. 998 -0. 105 0. 00 0. .00 0

ATOM 4420 CB ARG 283 24. 763 34. 843 -0. 177 0. 00 0. 00 c

ATOM 4421 CG ARG 283 24. 012 34. 240 1. 039 0. 00 0. ,00 c

ATOM 4422 CD ARG 283 24. .861 33. ,266 1. .889 0. 00 0, ,00 c

ATOM 4423 NE ARG 283 25. 334 32. 118 1. 072 0. 00 0. ,00 N

ATOM 4424 CZ ARG 283 26. ,359 31. .320 1. ,320 0. 00 0, ,00 C

ATOM 4425 NH1 ARG 283 27. ,118 31. .385 2. ,366 0. ,00 0, ,00 N

ATOM 4426 NH2 ARG 283 26. 609 30. 406 0. ,455 0. 00 0, .00 N

ATOM 4427 H ARG 283 25. ,700 35. ,697 -2. ,404 0. 00 0, .00 H

ATOM 4428 HA ARG 283 22. ,982 35. ,595 -1. ,180 0. ,00 0. .00 H

ATOM 4429 1HB ARG 283 25. ,740 35. ,252 0. ,153 0. 00 0, .00 H

ATOM 4430 2HB ARG 283 25. ,022 34, ,001 -0. ,851 0. ,00 0, .00 H

ATOM 4431 1HG ARG 283 23. .078 33, ,743 0, .704 0. ,00 0, ,00 H

ATOM 4432 2HG ARG 283 23. ,656 35. ,060 1. ,696 0. ,00 0. ,00 H

ATOM 4433 1HD ARG 283 24. .245 32, .900 2. .738 0. ,00 0, .00 H

ATOM 4434 2HD ARG 283 25. .701 33. .824 2, .349 0. ,00 0, .00 H

ATOM 4435 HE ARG 283 24, ,856 31, ,875 0, ,191 1. ,00 0, .00 H

ATOM 4436 IHHl ARG 283 27, ,989 30, .836 2, ,327 0. ,00 0, .00 H

ATOM 4437 2HH1 ARG 283 26, .919 32, ,150 3, ,021 0, ,00 0, .00 H

ATOM 4438 1HH2 ARG 283 27, .501 29, .903 0, .585 0. ,00 0, .00 H

ATOM 4439 2HH2 ARG 283 26, .041 30. .423 -0, .398 0. .00 0, .00 H

ATOM 4440 N ILE 284 22, .822 37. .698 0, .283 0. .00 0, .00 N

ATOM 4441 CA ILE 284 22, .635 38, .998 1, .002 0, .00 0, .00 C

ATOM 4442 C ILE 284 23, .475 39, .152 2, ,326 0, .00 0, .00 C

ATOM 4443 O ILE 284 23, .706 38, .191 3, .063 0, ,00 0, .00 O

ATOM 4444 CB ILE 284 21 .102 39, .312 1 , .209 0, .00 0. .00 C

ATOM 4445 CG2 ILE 284 20, .437 39, .829 -0, .094 0. .00 0, .00 C

ATOM 4446 CGI ILE 284 20 .202 38, .182 1, .792 0, .00 0 .00 c

ATOM 4447 CD1 ILE 284 20 .615 37 .641 3 .166 0, .00 0 .00 c

ATOM 4448 H ILE 284 22, .039 37, .050 0, .134 0. .00 0, .00 H

ATOM 4449 HA ILE 284 23 .025 39, .777 0, .318 0, .00 0 .00 H

ATOM 4450 HB ILE 284 21 .029 40 .155 1 .925 0, .00 0 .00 H

ATOM 4451 1HG2 ILE 284 19, .378 40, .117 0, .065 0, .00 0 .00 H

ATOM 4452 2HG2 ILE 284 20 .947 40 .714 -0 .511 0, .00 0 .00 H

ATOM 4453 3HG2 ILE 284 20 .424 39 .054 -0 .885 0, .00 0 .00 H

ATOM 4454 1HG1 ILE 284 20 .145 37, .338 1 .083 0, .00 0 .00 H

ATOM 4455 2HG1 ILE 284 19 .157 38 .547 1 .868 0, .00 0 .00 H

ATOM 4456 1HD1 ILE 284 19 .790 37 .070 3 .628 0 .00 0 .00 H

ATOM 4457 2HD1 ILE 284 21 .480 36 .956 3 .095 0, .00 0 .00 H

ATOM 4458 3HD1 ILE 284 20 .885 38 .454 3 .862 0, .00 0 .00 H

ATOM 4459 N SER 285 23 .929 40 .381 2 .628 0 .00 0 .00 N

ATOM 4460 CA SER 285 24 .651 40 .691 3 .896 0, .00 0 .00 C

ATOM 4461 C SER 285 23 .714 40 .879 5 .139 0 .00 0 .00 C

ATOM 4462 O SER 285 22 .522 41 .167 5 .002 0 .00 0 .00 O

ATOM 4463 CB SER 285 25 .538 41 .936 3 .621 0 .00 0 .00 C

ATOM 4464 OG SER 285 24 .768 43 .130 3 .430 0 .00 0 .00 O

ATOM 4465 H SER 285 23 .622 41 .112 1 .988 0 .00 0 .00 H

ATOM 4466 HA SER 285 25 .332 39 .846 4 .127 0 .00 0 .00 H

ATOM 4467 1HB SER 285 26 .195 41 .751 2 .747 0 .00 0 .00 H

ATOM 4468 2HB SER 285 26 .231 42 .087 4 .472 0 .00 0 .00 H

ATOM 4469 HG SER 285 25 .245 43 .669 2 .794 0 .00 0 .00 H

ATOM 4470 N ALA 286 24 .258 40 .763 6 .367 0 .00 0 .00 N

ATOM 4471 CA ALA 286 23 .472 40 .984 7 .620 0 .00 0 .00 C

ATOM 4472 C ALA 286 22 .734 42 .363 7 .802 0 .00 0 .00 C

ATOM 4473 O ALA 286 21 .611 42 .377 8 .305 0 .00 0 .00 O

ATOM 4474 CB ALA 286 24 .420 40 .641 8 .783 0 .00 0 .00 C

ATOM 4475 H ALA 286 25 .239 40 .475 6 .401 0 .00 0 .00 H

ATOM 4476 HA ALA 286 22 .664 40 .227 7 .641 0 .00 0 .00 H

ATOM 4477 1HB ALA 286 23 .893 40 .692 9 .755 0 .00 0 .00 H

ATOM 4478 2HB ALA 286 24 .841 39 .620 8 .712 0 .00 0 .00 H

ATOM 4479 3HB ALA 286 25 .270 41 .347 8 .856 0 .00 0 .00 H

ATOM 4480 N PHE 287 23 .307 43 .490 7 .337 1 .00 0, .00 N

ATOM 4481 CA PHE 287 22 .568 44 .780 7 .158 1 .00 0 .00 C

ATOM 4482 C PHE 287 21 .399 44 .757 6 .099 1 .00 0 .00 C ATOM 4483 O PHE 287 20.295 45.219 6.396 1.00 0.00 0

ATOM 4484 CB PHE 287 23. 653 45. 855 6. 845 1. 00 0. 00 c

ATOM 4485 CG PHE 287 23. 180 47. 316 6. 926 1. 00 0. 00 c

ATOM 4486 CD1 PHE 287 23. 243 48. 011 8. 139 1. 00 0. 00 C

ATOM 4487 CE1 PHE 287 22. 805 49. 332 8. 215 1. 00 0. 00 c

ATOM 4488 CZ PHE 287 22. 305 49. 966 7. 080 1. 00 0. 00 c

ATOM 4489 CE2 PHE 287 22. 247 49. 284 5. 868 1. 00 0. 00 c

ATOM 4490 CD2 PHE 287 22. 684 47. 964 5. 790 1. 00 0. .00 c

ATOM 4491 H PHE 287 24. 297 43. 381 7. 104 1. 00 0. .00 H

ATOM 4492 HA PHE 287 22. ,114 45. 043 8. 136 1. 00 0. .00 H

ATOM 4493 1HB PHE 287 24. ,498 45. ,743 7. 556 1. 00 0. ,00 H

ATOM 4494 2HB PHE 287 24. ,110 45. ,659 5. ,858 1. ,00 0. ,00 H

ATOM 4495 HD1 PHE 287 23. ,618 47. ,518 9. ,030 1. ,00 0. .00 H

ATOM 4496 HE1 PHE 287 22. ,847 49. ,857 9. ,160 1. ,00 0, .00 H

ATOM 4497 HZ PHE 287 21, ,957 50. ,987 7. ,147 1. ,00 0, .00 H

ATOM 4498 HE2 PHE 287 21. .844 49. ,772 4. ,993 1. ,00 0. .00 H

ATOM 4499 HD2 PHE 287 22. .603 47. ,437 4. ,851 1. ,00 0. .00 H

ATOM 4500 N ARG 288 21. .630 44. ,223 4, .885 1. .00 0, ,00 N

ATOM 4501 CA ARG 288 20. .557 44. .013 3, .860 1. .00 0, .00 C

ATOM 4502 C ARG 288 19. .388 43, .046 4, .275 1, .00 0, .00 C

ATOM 4503 O ARG 288 18. .231 43, .324 3. ,953 1, .00 0, .00 O

ATOM 4504 CB ARG 288 21, .223 43, .548 2, ,534 1, .00 0, .00 C

ATOM 4505 CG ARG 288 22, .155 44, .580 1, .850 1, .00 0, .00 C

ATOM 4506 CD ARG 288 22, .803 44, .037 0, .567 1, ,00 0, .00 C

ATOM 4507 NE ARG 288 23, .830 45, .012 0, .117 1, ,00 0 .00 N

ATOM 4508 CZ ARG 288 24, .317 45, .121 -1, .114 1. .00 0. .00 C

ATOM 4509 NH1 ARG 288 23, .977 44, .358 -2. ,109 1. .00 0, .00 N

ATOM 4510 NH2 ARG 288 25, .183 46, .048 -1, ,329 1. ,00 0, .00 N

ATOM 4511 H ARG 288 22, .530 43, .734 4, ,846 1, ,00 0, .00 H

ATOM 4512 HA ARG 288 20, .069 44, .992 3, .673 1, ,00 0, .00 H

ATOM 4513 1HB ARG 288 21, .766 42, .600 2, .725 1, ,00 0, .00 H

ATOM 4514 2HB ARG 288 20. .421 43, .270 1, .820 1. .00 0, .00 H

ATOM 4515 1HG ARG 288 21 .577 45, .503 1, .634 1, .00 0 .00 H

ATOM 4516 2HG ARG 288 22 .927 44 .889 2, .583 1, .00 0 .00 H

ATOM 4517 1HD ARG 288 23 .265 43 .045 0. .758 1, .00 0 .00 H

ATOM 4518 2HD ARG 288 22 .007 43 .868 -0. .190 1, .00 0 .00 H

ATOM 4519 HE ARG 288 24 .169 45 .731 0, .764 1, .00 0 .00 H

ATOM 4520 2HH1 ARG 288 23 .284 43 .642 -1 .872 1, .00 0 .00 H

ATOM 4521 IHHl ARG 288 24 .403 44 .513 -3 .023 1, .00 0 .00 H

ATOM 4522 1HH2 ARG 288 25 .418 46 .647 -0 .536 1, .00 0 .00 H

ATOM 4523 2HH2 ARG 288 25 .544 46 .132 -2 .280 1, .00 0 .00 H

ATOM 4524 N ALA 289 19 .666 41 .955 5 .014 0, .00 0 .00 N

ATOM 4525 CA ALA 289 18 .637 41 .150 5 .734 0 .00 0 .00 C

ATOM 4526 C ALA 289 17 .698 41 .947 6 .702 0, .00 0 .00 C

ATOM 4527 O ALA 289 16 .500 41 .657 6 .750 0 .00 0 .00 O

ATOM 4528 CB ALA 289 19 .393 40 .001 6 .417 0, .00 0 .00 C

ATOM 4529 H ALA 289 20 .671 41 .817 5 .188 0 .00 0 .00 H

ATOM 4530 HA ALA 289 17 .969 40 .701 4 .970 0 .00 0 .00 H

ATOM 4531 1HB ALA 289 18 .695 39 .286 6 .890 0 .00 0 .00 H

ATOM 4532 2HB ALA 289 19 .997 39 .418 5 .699 0 .00 0 .00 H

ATOM 4533 3HB ALA 289 20 .078 40 .368 7 .204 0, .00 0 .00 H

ATOM 4534 N LEU 290 18 .221 42 .933 7 .464 0, .00 0 .00 N

ATOM 4535 CA LEU 290 17 .380 43 .842 8 .302 0, .00 0 .00 C

ATOM 4536 C LEU 290 16 .359 44 .671 7 .427 0, .00 0 .00 C

ATOM 4537 O LEU 290 15 .193 44 .809 7 .798 0, .00 0 .00 0

ATOM 4538 CB LEU 290 18 .264 44 .836 9 .121 0, .00 0 .00 c

ATOM 4539 CG LEU 290 19 .369 44 .305 10 .067 0, .00 0 .00 c

ATOM 4540 CD1 LEU 290 20 .130 45 .470 10 .720 0, .00 0 .00 c

ATOM 4541 CD2 LEU 290 18 .829 43 .386 11 .165 0, .00 0 .00 c

ATOM 4542 H LEU 290 19 .230 43 .080 7 .326 0, .00 0 .00 H

ATOM 4543 HA LEU 290 16 .783 43 .228 9 .003 0, .00 0 .00 H

ATOM 4544 1HB LEU 290 17 .598 45 .497 9 .700 0, .00 0 .00 H

ATOM 4545 2HB LEU 290 18 .758 45 .522 8 .404 0, .00 0 .00 H

ATOM 4546 HG LEU 290 20 .098 43 .735 9 .465 0. .00 0 .00 H

ATOM 4547 1HD1 LEU 290 20 .971 45 .109 11 .346 0, .00 0 .00 H ATOM 4548 2HD1 LEU 290 20.604 46.121 9.959 0.00 0.00 H

ATOM 4549 3HD1 LEU 290 19. 497 46. 114 11. 352 0. 00 0. 00 H

ATOM 4550 1HD2 LEU 290 19. 656 42. 992 11. 785 0. 00 0. 00 H

ATOM 4551 2HD2 LEU 290 18. 122 43. 895 11. 836 0. 00 0. 00 H

ATOM 4552 3HD2 LEU 290 18. 326 42. 505 10. 727 0. 00 0. 00 H

ATOM 4553 N GLN 291 16. 779 45. 187 6. 258 0. 00 0. 00 N

ATOM 4554 CA GLN 291 15. 929 46. 033 5. 363 0. 00 0. 00 C

ATOM 4555 c GLN 291 14. 900 45. ,286 4. .416 0. 00 0. .00 C

ATOM 4556 O GLN 291 14. 542 45. ,816 3. ,359 0. 00 0. .00 O

ATOM 4557 CB GLN 291 16. 931 46. ,909 4. ,543 0. 00 0. ,00 C

ATOM 4558 CG GLN 291 17. 883 47. ,867 5. ,320 0. 00 0. ,00 C

ATOM 4559 CD GLN 291 18. ,860 48. ,621 4. ,414 0. 00 0. .00 C

ATOM 4560 OE1 GLN 291 19. ,788 48, ,063 3, .841 0. 00 0. .00 O

ATOM 4561 NE2 GLN 291 18. ,692 49, .907 4, .240 0. 00 0. .00 N

ATOM 4562 H GLN 291 17. ,738 44. ,918 6. .008 0. 00 0. ,00 H

ATOM 4563 HA GLN 291 15. ,312 46. .717 5, ,977 0. 00 0. .00 H

ATOM 4564 1HB GLN 291 17. ,534 46, .239 3. .896 0. 00 0, .00 H

ATOM 4565 2HB GLN 291 16. ,351 47. .524 3, .827 0. 00 0. .00 H

ATOM 4566 1HG GLN 291 17. ,298 48. ,564 5, .948 0. 00 0, .00 H

ATOM 4567 2HG GLN 291 18. .503 47. ,292 6, .033 0. 00 0. .00 H

ATOM 4568 1HE2 GLN 291 19, ,367 50. .336 3. .605 0. ,00 0, .00 H

ATOM 4569 2HE2 GLN 291 17. .898 50. .336 4, .719 0. ,00 0, .00 H

ATOM 4570 N HIS 292 14. .382 44, .096 4, .782 0. ,00 0, .00 N

ATOM 4571 CA HIS 292 13. .439 43, .305 3, .936 0. .00 0, .00 C

ATOM 4572 C HIS 292 11, .943 43, .429 4, .403 0. .00 0, .00 C

ATOM 4573 O HIS 292 11, .648 43, .440 5, .600 0. .00 0, .00 O

ATOM 4574 CB HIS 292 13, .949 41, .833 3, .959 0. .00 0, .00 C

ATOM 4575 CG HIS 292 13, .373 40, .951 2, .849 0. .00 0 .00 C

ATOM 4576 ND1 HIS 292 12, .113 40, .370 2 .900 0. ,00 0 .00 N

ATOM 4577 CE1 HIS 292 12 .079 39 .796 1 .655 0, ,00 0 .00 C

ATOM 4578 NE2 HIS 292 13, .158 39, .920 0, .823 0, ,00 0, .00 N

ATOM 4579 CD2 HIS 292 13, .998 40, .672 1, .622 0, .00 0, .00 C

ATOM 4580 H HIS 292 14, .713 43, .765 5, .694 0. .00 0 .00 H

ATOM 4581 HA HIS 292 13, .508 43 .659 2, .885 0. ,00 0 .00 H

ATOM 4582 1HB HIS 292 13. .742 41 .368 4. .942 0, .00 0 .00 H

ATOM 4583 2HB HIS 292 15 .053 41 .805 3 .870 0, ,00 0 .00 H

ATOM 4584 HE1 HIS 292 11 .215 39 .221 1 .344 0, ,00 0 .00 H

ATOM 4585 HE2 HIS 292 13 .377 39 .473 -0 .078 0. .00 0 .00 H

ATOM 4586 HD2 HIS 292 14 .994 40 .984 1 .335 0 .00 0 .00 H

ATOM 4587 N SER 293 11 .002 43 .416 3 .425 1 .00 0 .00 N

ATOM 4588 CA SER 293 9 .523 43 .430 3 .675 1 .00 0 .00 C

ATOM 4589 C SER 293 8 .927 42 .459 4 .754 1 .00 0 .00 C

ATOM 4590 O SER 293 7 .866 42 .787 5 .293 1 .00 0 .00 O

ATOM 4591 CB SER 293 8 .780 43 .376 2 .324 1 .00 0 .00 C

ATOM 4592 OG SER 293 7 .383 43 .623 2 .503 1 .00 0 .00 O

ATOM 4593 H SER 293 11 .388 43 .274 2 .486 1 .00 0 .00 H

ATOM 4594 HA SER 293 9 .307 44 .436 4 .087 1 .00 0 .00 H

ATOM 4595 1HB SER 293 9 .187 44 .120 1 .612 1 .00 0 .00 H

ATOM 4596 2HB SER 293 8 .926 42 .387 1 .844 1 .00 0 .00 H

ATOM 4597 HG SER 293 7 .117 43 .220 3 .342 1 .00 0 .00 H

ATOM 4598 N TYR 294 9 .493 41 .256 4 .995 0 .00 0 .00 N

ATOM 4599 CA TYR 294 9 .043 40 .421 6 .155 0 .00 0 .00 C

ATOM 4600 C TYR 294 9 .199 41 .090 7 .574 0 .00 0 .00 C

ATOM 4601 O TYR 294 8 .359 40 .876 8 .447 0 .00 0 .00 0

ATOM 4602 CB TYR 294 9 .811 39 .064 6 .062 0 .00 0 .00 c

ATOM 4603 CG TYR 294 9 .418 37 .961 7 .076 0 .00 0 .00 c

ATOM 4604 GDI TYR 294 8 .105 37 .485 7 .166 0 .00 0 .00 c

ATOM 4605 CE1 TYR 294 7 .758 36 .545 8 .136 0 .00 0 .00 c

ATOM 4606 CZ TYR 294 8 .723 36 .072 9 .021 0 .00 0 .00 c

ATOM 4607 OH TYR 294 8 .366 35 .208 10 .019 0 .00 0 .00 0

ATOM 4608 CE2 TYR 294 10 .036 36 .512 8 .921 0 .00 0 .00 c

ATOM 4609 CD2 TYR 294 10 .387 37 .443 7 .945 0 .00 0 .00 c

ATOM 4610 H TYR 294 10 .307 41 .033 4 .407 1 .00 0 .00 H

ATOM 4611 HA TYR 294 7 .962 40 .209 6 .028 0 .00 0 .00 H

ATOM 4612 1HB TYR 294 10 .900 39 .260 6 .107 0 .00 0 .00 H ATOM 4613 2HB TYR 294 9 ,668 38.639 052 0.00 00 H

ATOM 4614 HD1 TYR 294 7.335 37.850 497 0.00 00 H

ATOM 4615 HE1 TYR 294 6 ,734 36.202 8.210 0.00 00 H

ATOM 4616 HH TYR 294 9.057 35.183 10.683 0.00 00 H

ATOM 4617 HE2 TYR 294 10.787 36.142 603 00 00 H

ATOM 4618 HD2 TYR 294 11.412 37.774 880 00 00 H

ATOM 4619 N LEU 295 10.292 41.831 820 00 00 N

ATOM 4620 CA LEU 295 10.765 42.219 175 00 00 C

ATOM 4621 C LEU 295 10.687 43.768 399 00 00 c

ATOM 4622 O LEU 295 11.265 44.545 8.632 ,00 00 O

ATOM 4623 CB LEU 295 12.261 41.789 9.312 00 00 c

ATOM 4624 CG LEU 295 12.665 40.301 9.145 00 0.00 c

ATOM 4625 GDI LEU 295 14.193 40.174 9.086 00 0.00 c

ATOM 4626 CD2 LEU 295 12.132 39.412 10.275 00 00 c

ATOM 4627 H LEU 295 10.815 42.079 6.968 ,00 00 H

ATOM 4628 HA LEU 295 10.180 41.697 9.959 ,00 00 H

ATOM 4629 1HB LEU 295 12.849 42.381 8.580 .00 00 H

ATOM 4630 2HB LEU 295 12.619 42.122 10.302 .00 00 H

ATOM 4631 HG LEU 295 12.264 39.930 8.180 ,00 00 H

ATOM 4632 2HD1 LEU 295 14.512 39.123 8.959 ,00 00 H

ATOM 4633 3HD1 LEU 295 14.612 40.728 8.224 1.00 00 H

ATOM 4634 1HD1 LEU 295 14.689 40.556 9.995 00 00 H

ATOM 4635 2HD2 LEU 295 12.420 39.762 11.281 00 00 H

ATOM 4636 3HD2 LEU 295 11.032 39.368 10.251 00 00 H

ATOM 4637 1HD2 LEU 295 12.481 38.366 10.183 00 00 H

ATOM 4638 N HIS 296 10.028 44.225 10.474 0.00 00 N

ATOM 4639 CA HIS 296 9.934 45.679 10.810 0.00 0.00 c

ATOM 4640 C HIS 296 10.219 45.870 12.335 00 0.00 c

ATOM 4641 O HIS 296 9.417 45.452 13.174 00 00 0

ATOM 4642 CB HIS 296 8.565 46.263 10.339 00 00 c

ATOM 4643 CG HIS 296 8.695 47.235 9.169 00 00 c

ATOM 4644 ND1 HIS 296 8.786 48.609 9.338 00 00 N

ATOM 4645 CE1 HIS 296 9.026 48.975 8.039 00 00 c

ATOM 4646 NE2 HIS 296 9.100 48.022 7.059 00 00 N

ATOM 4647 CD2 HIS 296 8.890 46.886 7.821 00 0.00 c

ATOM 4648 H HIS 296 9.530 43.516 11.022 00 0.00 H

ATOM 4649 HA HIS 296 10.736 46.234 10.278 00 0.00 H

ATOM 4650 1HB HIS 296 7.841 45.471 10.074 00 00 H

ATOM 4651 2HB HIS 296 8.064 46.798 11.170 00 00 H

ATOM 4652 HE1 HIS 296 9.163 50.023 801 00 00 H

ATOM 4653 HE2 HIS 296 9.315 48.118 061 00 00 H

ATOM 4654 HD2 HIS 296 8.934 45.868 452 00 00 H

ATOM 4655 N LYS 297 11.382 46.446 12.676 00 0.00 N

ATOM 4656 CA LYS 297 11.899 46.550 14.063 0.00 0.00 C

ATOM 4657 C LYS 297 12.720 47.877 14.233 0.00 00 C

ATOM 4658 O LYS 297 13.228 48.488 13.286 00 00 O

ATOM 4659 CB LYS 297 12.728 45.262 14.346 00 00 C

ATOM 4660 CG LYS 297 13.358 45.130 15.750 00 00 C

ATOM 4661 CD LYS 297 14.170 43.836 15.920 00 00 C

ATOM 4662 CE LYS 297 15.022 43.893 17.193 00 00 C

ATOM 4663 NZ LYS 297 15.849 42.680 17.279 00 00 N

ATOM 4664 H LYS 297 11.842 46.942 11.908 00 00 H

ATOM 4665 HA LYS 297 11.042 46.590 14.772 00 0.00 H

ATOM 4666 1HB LYS 297 12.077 44.380 14.170 00 0.00 H

ATOM 4667 2HB LYS 297 13.529 45.203 13.597 00 00 H

ATOM 4668 1HG LYS 297 14.005 46.011 15.945 00 00 H

ATOM 4669 2HG LYS 297 12.562 45.185 16.525 00 00 H

ATOM 4670 1HD LYS 297 13.471 42.970 15.946 00 00 H

ATOM 4671 2HD LYS 297 14.808 43.691 15.033 00 00 H

ATOM 4672 1HE LYS 297 15.630 44.827 17.236 00 00 H

ATOM 4673 2HE LYS 297 14.341 43.973 18.080 00 00 H

ATOM 4674 1HZ LYS 297 16.391 42.604 18.151 00 00 H

ATOM 4675 2HZ LYS 297 15.239 41.844 17.322 00 00 H

ATOM 4676 3HZ LYS 297 16.478 42.497 16.489 00 00 H

ATOM 4677 N ASP 298 12.789 48.343 15.492 00 00 N ATOM 4678 CA ASP 298 13.498 49.,593 15.888 0.00 0.00 c

ATOM 4679 C ASP 298 14. 911 49. 330 16. 549 0. 00 0. 00 c

ATOM 4680 O ASP 298 15. 365 48. ,199 16. 747 0. 00 0. 00 0

ATOM 4681 CB ASP 298 12. 439 50. ,333 16. 771 0. 00 0. 00 c

ATOM 4682 CG ASP 298 12. 713 51. ,761 17. ,245 0. 00 0. ,00 c

ATOM 4683 OD1 ASP 298 12. ,287 52, ,209 18. ,301 0. ,00 0. ,00 0

ATOM 4684 OD2 ASP 298 13. 461 52. .490 16. 372 0. 00 0. .00 0

ATOM 4685 H ASP 298 12. 258 47. .824 16. ,195 1. 00 0. ,00 H

ATOM 4686 HA ASP 298 13. ,676 50, .234 15. .000 0. ,00 0. ,00 H

ATOM 4687 1HB ASP 298 11. ,475 50, ,407 16. .236 0. ,00 0. ,00 H

ATOM 4688 2HB ASP 298 12. 225 49. .743 17. ,681 0. 00 0. ,00 H

ATOM 4689 N GLU 299 15. ,612 50. .427 16. ,857 0. .00 0. ,00 N

ATOM 4690 CA GLU 299 16. ,969 50. .453 17. ,488 0. ,00 0. ,00 C

ATOM 4691 C GLU 299 16, ,934 51. .258 18, .844 0. ,00 0, .00 C

ATOM 4692 O GLU 299 16. ,093 52, .150 19. .007 0. ,00 0. .00 O

ATOM 4693 CB GLU 299 17. ,992 50. .848 16. .387 0. ,00 0. .00 C

ATOM 4694 CG GLU 299 17, .754 52, .124 15, .523 0. ,00 0. .00 c

ATOM 4695 CD GLU 299 18, .334 52, .048 14, .110 0. .00 0. .00 C

ATOM 4696 OE1 GLU 299 17, .659 52, .120 13, ,088 0. .00 0, .00 0

ATOM 4697 OE2 GLU 299 19, .682 51, .875 14. .099 0, .00 0, .00 0

ATOM 4698 H GLU 299 15, ,054 51, .298 16. ,773 1. .00 0. .00 H

ATOM 4699 HA GLU 299 17. ,237 49, .423 17, .792 0, .00 0, .00 H

ATOM 4700 1HB GLU 299 19, .007 50 .901 16, .823 0, .00 0, .00 H

ATOM 4701 2HB GLU 299 18. ,023 49, .988 15. ,700 0. .00 0, .00 H

ATOM 4702 1HG GLU 299 16. .678 52, .350 15, .405 0, ,00 0, .00 H

ATOM 4703 2HG GLU 299 18. .165 53 .021 16, .020 0, .00 0, .00 H

ATOM 4704 N GLY 300 17. .848 50 .993 19, .813 0, .00 0, .00 N

ATOM 4705 CA GLY 300 17, .741 51, .624 21, ,160 0, ,00 0, .00 C

ATOM 4706 C GLY 300 18, .723 52. .767 21, .503 0, .00 0, .00 C

ATOM 4707 O GLY 300 19, .921 52 .662 21, .246 0, .00 0, .00 O

ATOM 4708 H GLY 300 18, .581 50 .334 19, .550 1, .00 0, .00 H

ATOM 4709 1HA GLY 300 16, .699 51 .951 21, .363 0, .00 0, .00 H

ATOM 4710 2HA GLY 300 17, .912 50 .843 21, .920 0. .00 0, .00 H

ATOM 4711 N ASN 301 18, .229 53 .813 22, .188 0, .00 0, .00 N

ATOM 4712 CA ASN 301 19 .094 54 .891 22, .758 0. .00 0 .00 C

ATOM 4713 C ASN 301 18 .637 55 .248 24 .218 0 .00 0 .00 C

ATOM 4714 O ASN 301 17, .482 55 .665 24, .361 0, .00 0, .00 O

ATOM 4715 CB ASN 301 19 .048 56 .171 21, .876 0, .00 0, .00 C

ATOM 4716 CG ASN 301 19 .626 56 .036 20 .469 0 .00 0 .00 C

ATOM 4717 OD1 ASN 301 18 .965 55 .607 19 .533 0 .00 0 .00 O

ATOM 4718 ND2 ASN 301 20 .862 56 .395 20, .252 0, .00 0, .00 N

ATOM 4719 H ASN 301 17 .204 53 .886 22 .216 1, .00 0 .00 H

ATOM 4720 HA ASN 301 20 .147 54 .558 22 .786 0 .00 0 .00 H

ATOM 4721 1HB ASN 301 17 .997 56 .506 21 .770 0 .00 0 .00 H

ATOM 4722 2HB ASN 301 19 .535 57 .015 22. .400 0, .00 0. .00 H

ATOM 4723 1HD2 ASN 301 21 .151 56 .265 19 .281 0 .00 0 .00 H

ATOM 4724 2HD2 ASN 301 21 .366 56 .796 21 .045 0 .00 0 .00 H

ATOM 4725 N PRO 302 19 .444 55 .109 25 .320 0 .00 0 .00 N

ATOM 4726 CA PRO 302 19 .059 55 .645 26 .659 0 .00 0 .00 C

ATOM 4727 CD PRO 302 20 .781 54 .481 25 .304 0 .00 0 .00 C

ATOM 4728 C PRO 302 19 .016 57 .213 26 .661 0 .00 0 .00 C

ATOM 4729 O PRO 302 19 .968 57 .890 26 .255 0 .00 0 .00 O

ATOM 4730 CB PRO 302 20 .095 54 .986 27 .585 0 .00 0 .00 C

ATOM 4731 CG PRO 302 21 .327 54 .744 26 .711 0 .00 0 .00 c

ATOM 4732 HA PRO 302 18 .056 55 .254 26 .926 0 .00 0 .00 H

ATOM 4733 1HD PRO 302 21 .450 54 .924 24 .541 0 .00 0 .00 H

ATOM 4734 2HD PRO 302 20 .695 53 .396 25 .100 0 .00 0 .00 H

ATOM 4735 1HB PRO 302 20 .315 55 .602 28 .478 0 .00 0 .00 H

ATOM 4736 2HB PRO 302 19 .697 54 .022 27 .957 0 .00 0 .00 H

ATOM 4737 1HG PRO 302 21 .950 55 .660 26 .698 0 .00 0 .00 H

ATOM 4738 2HG PRO 302 21 .967 53 .922 27 .082 0 .00 0 .00 H

ATOM 4739 N GLU 303 17 .873 57 .751 27 .089 0 .00 0 .00 N

ATOM 4740 CA GLU 303 17 .581 59 .206 27, .092 0, .00 0, .00 C

ATOM 4741 C GLU 303 16 .750 59 .655 28, .326 0, .00 0, .00 C

ATOM 4742 O GLU 303 15 .880 58 .896 28, .823 0, .00 0. .00 O ATOM 4743 OXT GLU 303 16..966 60,,796 28,,796 0,.00 0,,00 0

ATOM 4744 CB GLU 303 16. ,877 59, .524 25. .733 0, .00 0. ,00 c

ATOM 4745 CG GLU 303 15, .539 58, .773 25. ,424 0, .00 0, .00 c

ATOM 4746 CD GLU 303 15, .007 58, .766 23, .991 0, .00 0, .00 c

ATOM 4747 OE1 GLU 303 14, .234 57. .914 23, .562 0 .00 0, .00 0

ATOM 4748 OE2 GLU 303 15, .465 59, .796 23, .229 0 .00 0, .00 o

ATOM 4749 H GLU 303 17, .132 57, .114 27, .389 1 .00 0, .00 H

ATOM 4750 HA GLU 303 18 .523 59 .786 27 .132 0 .00 0, .00 H

ATOM 4751 1HB GLU 303 16, .696 60. .612 25, .667 0, .00 0, .00 H

ATOM 4752 2HB GLU 303 17, .591 59, .315 24, .914 0 .00 0, .00 H

ATOM 4753 1HG GLU 303 15, .632 57, .708 25, .687 0, .00 0, .00 H

ATOM 4754 2HG GLU 303 14, .740 59, .156 26, .078 0 .00 0, .00 H

Table 2. PDB coordinate file of compound [9].

ATOM 4755 c C5K5 304 28, ,312 29, .833 26, .191 0, ,00 0. .00 c

ATOM 4756 CI C5K5 304 27, ,080 29, .474 26. .711 0. .00 0, .00 c

ATOM 4757 S C5K5 304 26, .580 27. ,952 26. ,041 0. .00 0. ,00 s

ATOM 4758 C2 C5K5 304 27, .993 27. ,910 25. ,090 0, .00 0. .00 c

ATOM 4759 N C5K5 304 28, .329 26. .853 24. ,191 0. .00 0. .00 N

ATOM 4760 CM C5K5 304 27. .368 25, .792 23. ,834 0. ,00 0, .00 c

ATOM 4761 Nl C5K5 304 28, .827 28. .940 25. .281 0, .00 0. .00 N

ATOM 4762 G3 C5K5 304 29, .177 30. .985 26. .680 0, .00 0. ,00 C

ATOM 4763 C4 C5K5 304 26, .244 30. .063 27. .691 0, .00 0, .00 C

ATOM 4764 C5 C5K5 304 26, .190 31. .451 27. .975 0, .00 0. .00 C

ATOM 4765 N2 C5K5 304 24, .323 31. .006 29, .395 0, .00 0, .00 N

ATOM 4766 C6 C5K5 304 25, .167 31. .880 28, .849 0, .00 0, .00 C

ATOM 4767 N3 C5K5 304 25, .419 29. .247 28, .321 0, .00 0, .00 N

ATOM 4768 C7 C5K5 304 24, .458 29. .733 29, .077 0, .00 0, .00 C

ATOM 4769 N4 C5K5 304 23. .340 28, .855 29, .401 0, .00 0, ,00 N

ATOM 4770 C8 C5K5 304 21, .385 25, .699 28, ,721 0, .00 0, ,00 C

ATOM 4771 C9 C5K5 304 21, .708 27, ,006 29, .118 0, .00 0. .00 C

ATOM 4772 CIO C5K5 304 23, .030 27, .458 29. ,055 0, ,00 0, .00 c

ATOM 4773 Cll C5K5 304 24, .018 26, .574 28. .614 0, .00 0. .00 c

ATOM 4774 C12 C5K5 304 23, .695 25, .304 28, .187 0, .00 0, .00 c

ATOM 4775 C13 C5K5 304 22, .387 24, .821 28, .270 0, .00 0, .00 c

ATOM 4776 N13 C5K5 304 22 .100 23, .402 27, .923 0, .00 0, .00 N

ATOM 4777 C15 C5K5 304 23 .191 22, .380 27, .758 0 .00 0, .00 C

ATOM 4778 C16 C5K5 304 23 .597 22, .239 26, .257 0 .00 0, .00 C

ATOM 4779 C17 C5K5 304 20 .857 23, .025 27, .158 0 .00 0, .00 C

ATOM 4780 C18 C5K5 304 21 .082 22 .111 25, .892 0 .00 0, .00 C

ATOM 4781 N183 C5K5 304 22, .445 22, .287 25, .296 0, .00 0. .00 N

ATOM 4782 HN C5K5 304 29 .129 27, .062 23, .559 0, .00 0, .00 H

ATOM 4783 IBM C5K5 304 27 .153 25, .116 24, .684 0, .00 0, .00 H

ATOM 4784 2HM C5K5 304 27 .748 25, .171 22, .999 0, .00 0, .00 H

ATOM 4785 3HM C5K5 304 26 .401 26, .211 23, .491 0, .00 0, .00 H

ATOM 4786 3H3 C5 5 304 29 .186 31, .059 27, .782 0 .00 0, .00 H

ATOM 4787 1H3 C5 5 304 30 .229 30, .890 26, .354 0 .00 0, .00 H

ATOM 4788 2H3 C5K5 304 28 .816 31 .950 26, .283 0 .00 0, .00 H

ATOM 4789 H5 C5 5 304 26 .827 32 .171 27, .488 0 .00 0, .00 H

ATOM 4790 H6 C5K5 304 25 .039 32 .935 29 .041 0 .00 0, .00 H

ATOM 4791 H4 C5K5 304 22 .535 29 .394 29 .756 0 .00 0, .00 H

ATOM 4792 H8 C5K5 304 20 .361 25 .368 28 .789 0 .00 0 .00 H

ATOM 4793 H9 C5K5 304 20, .925 27, .669 29, .456 0, .00 0, .00 H

ATOM 4794 Hll C5K5 304 25, .063 26, .826 28, .607 0, .00 0. .00 H

ATOM 4795 HI2 C5K5 304 24 .497 24, .695 27, .807 0, .00 0, .00 H

ATOM 4796 1H16 C5K5 304 24, .176 21, .306 26, .108 0, .00 0, .00 H

ATOM 4797 2H16 C5K5 304 24 .302 23, .053 25, .997 0, .00 0, .00 H

ATOM 4798 1H15 C5K5 304 24 .070 22, .599 28, .392 0, .00 0, .00 H

ATOM 4799 2H15 C5K5 304 22 .833 21, .404 28, .137 0, .00 0, .00 H

ATOM 4800 1H18 C5K5 304 20 .321 22, .339 25, .121 0, .00 0, .00 H

ATOM 4801 2H18 C5K5 304 20 .925 21, .050 26, .164 0, .00 0, .00 H ATOM 4802 3H18 C5K5 304 22 385 23 254 24 897 0 00 0 00 H ATOM 4803 3H18 C5K5 304 22 656 21 737 24 434 0 00 0 00 H ATOM 4804 1H17 C5K5 304 20 138 22 545 27 845 0 00 0 00 H ATOM 4805 2H17 C5K5 304 20 334 23 940 26 817 0 00 0 00 H

Table 3. Comparison ofthe ATP contacting residues in for CDK2 and CDK4. Residues which are conservative mutations with respect to CDK2 are marked in italics and those that are non-conservative with respect to CDK2 are marked in bold.

Table 4. In vitro potencies, pKa and selectivity ratios for aminopyrimidine compounds

Structure Kinase inhibition (μM)

ty

R¹ R² R³ 1 NELMe H CH2NH2 9.6 0.23 0.41 1.8 2 NHEt H CH2NH2 9.6 0.11 0.33 3.0 3 NHMe H CH2NHAC - 0.89 0.43 0.5 4 Me NH_ H 4.0 3.8 0.23 0.1 5 Me N O H 3.7 4.0 2.0 0.5 6 Me N NH H 9.0 0.64 1.1 1.7 7 Me N N- H 7.3 0.16 1.02 6.4 OH 8 Me N N^ H 7.4 0.43 2.2 5.1

9 NHMe N Nh H 9.0 0.007 0.22 31.4 \ 1 Table 5. fritermolecular contacts for complex of compound [9] with CDK4 homology model.

Claims

1. A method of screening for a modulator of CDK4, wherein the method comprises using the stracture co-ordinates of Table 1.

2. A method according to claim 1 comprising the steps of:

(a) providing at least a portion of the stracture co-ordinates of Table 1 ;

(b) employing at least a portion ofthe structure co-ordinates of Table 1 to design or select or synthesise a putative modulator of CDK4;

(c) contacting the putative modulator of CDK4 with CDK4 or a mutant, variant, homologue, derivative or fragment thereof in the presence of a substrate; and

(d) determining whether said putative modulator of CDK4 modulates CDK4.

3. A method according to any preceding claim wherein at least a portion of the stracture co-ordinates of Table 1 and/or the putative modulator of CDK4 and/or the substrate are provided on a machine-readable data storage medium comprising a data storage material encoded with machine readable data.

4. A method according to claim 2 or claim 3 wherein the putative CDK4 modulator is from a library of compounds.

5. A method according claim 2 or claim 3 wherein the putative CDK4 modulator is selected from a database.

6. A method according to claim 2 or claim 3 wherein the putative CDK4 modulator is designed de novo.

7. A method according to claim 2 or claim 3 wherein the putative CDK4 modulator is designed from a known CDK4 modulator.

8. A method according to claim 2 or claim 3 wherein the design or selection of the putative CDK4 modulator is performed in conjunction with computer modelling.

9. A method according to any preceding claim wherein the modulator of CDK4 inhibits CDK4 activity.

10. A method according to any preceding claim wherein the the modulator of CDK4 is selective for CDK4 over CDK2.

11. A method according to any preceding claim wherein the CDK4 modulator is useful in the prevention and/or treatment of a CDK4 related disorder.

12. A method according to claim 11 wherein the CDK4 related disorder is a proliferative disorder.

13. A method according to claim 12 wherein the proliferative disorder is selected from cancer, leukemia, glomerulonephritis, rheumatoid arthritis, psoriasis and chronic obstructive pulmonary disorder.

14. An assay for a candidate compound capable of modulating CDK4, said assay comprising the steps of:

(a) contacting said candidate compound with CDK4;

(b) detecting whether said candidate compound forms associations with one or more amino acid residues conesponding to CDK4 amino acid residues V20, F93, D99, L147, E144 and D158.

15. An assay according to claim 14 wherein said candidate compound is selected by performing rational drag design with a 3-dimensional model of CDK4 in conjunction with computer modelling.

16. Use of a compound selected from the followmg:

HI PI [6]

17. Use according to claim 16 wherein the assay is a competitive binding assay.

18. Use according to claim 17 or claim 18 wherein the assay comprises contacting a candidate compound with CDK4 in the presence of a compound of formula [1], [2], [6]- [9], or a pharmaceutically acceptable salt thereof, and detecting any change in the interaction between said compound of formula [1], [2], [6]-[9] and CDK4.

19. A CDK4 modulator or candidate compound identified by the method of any one of claims 1 to 13 or the assay of any one of claims 14 to 18.

20. A CDK4 modulator according to claim 19 wherein the CDK4 modulator inhibits CDK4 activity.

21. A CDK4 modulator according to claim 20 wherein the CDK4 modulator selectively inhibits CDK4.

22. A CDK4 modulator according to claim 21 which has an ionizable functional group capable of forming associations with the amino acid residues conesponding to CDK4 amino acid residues D99 and El 44 of CDK4.

23. A CDK4 modulator according to claim 22 wherein the ionizable functional group is a group which is positively charged at physiological pH.

24. A CDK4 modulator according to claim 22 or claim 23 wherein the ionizable functional group is an NH group which is positively charged at physiological pH.

25. A CDK4 modulator according to any one of claims 21 to 24 which comprises a functional group capable of forming a hydrogen bond with the amino acid residue conesponding to D 158 of CDK4.

26. A CDK4 modulator according to any one of claims 21 to 25 which is capable of forming associations with one or more amino acid residues conesponding to V20, D99 and L147 ofCDK4.

27. A CDK4 modulator according to any one of claims 21 to 26 which comprises a group which is capable of sterically interacting with the amino acid residues conesponding to D86 and K89 ofthe ATP binding site of CDK2.

28. A pharmaceutical composition comprising a CDK4 modulator or compound according to any one of claims 19 to 27 and a pharmaceutically acceptable carrier, diluent, excipient or adjuvant or any combination thereof.

29. A method of preventing and/or treating an CDK4 related disorder comprising adnήnistering a modulator of CDK4 according to any one of claims 19 to 27 and/or a pharmaceutical composition according to claim 28 wherein said modulator of CDK4 or said pharmaceutical is capable of causing a beneficial preventative and/or therapeutic effect.

30. Use of a modulator of CDK4 or compound according to any one of claims 19 to

27 in the preparation of a medicament for treating a CDK4 related disorder.

31. A method according to claim 29, or use according to claim 30, wherein the CDK4 related disorder is cancer.

32. A process comprising the steps of:

(a) performing the method according to any of claims 1 to 13, or the assay of claims 14 to 18;

(b) identifying one or more modulators of CDK4; and

(c) preparing a quantity of said one or more CDK4 modulators.

33. A process comprising the steps of:

(b) identifying one or more CDK4 modulators; and

34. A process comprising the steps of:

(b) identifying one or more CDK4 modulators;

(c) modifying said one or more CDK4 modulators; and

35. A computer for producing a three-dimensional representation of CDK4 wherein said computer comprises:

(a) a computer-readable data storage medium comprising a data storage material encoded with computer-readable data, wherein said data comprises the structure co-ordinates of Table 1; (b) a working memory for storing instructions for processing said computer- readable data;

(c) a central-processing unit coupled to said working memory and to said computer-readable data storage medium for processing said computer-machine readable data into said three-dimensional representation; and

36. A machine-readable data storage medium comprising a data storage material encoded with machine readable data, wherein the data is defined by at least a portion of the structure co-ordinates of Table 1.

37. Use of the computer of claim 35 or the machine readable data storage medium of claim 36 to predict the stracture and/or function of potential modulators of CDK4.

38. Use of at least a portion of the stracture co-ordinates of Table 1 to screen for modulators of CDK4.

39. Use of at least a portion of the stracture co-ordinates of Table 1 in molecular design techniques to design, select and synthesise modulators of CDK4.

40. Use of at least a portion of the stracture co-ordinates of Table 1 in the development of compounds that can isomerise to reaction intermediates in the chemical reaction of a substrate or other compound that binds to CDK4.

41. Use of at least a portion of the stracture co-ordinates of Table 1 to screen small molecule databases for chemical entities or compounds that modulate CDK4.

42. Use according to any one of claims 37 to 41 wherein the modulator of CDK4, chemical entity, substrate or compound selectively inhibits the activity of CDK4.

43. Use of at least a portion of the stracture co-ordinates of Table 1 to solve the stracture of the crystalline form of a protein with significant amino acid sequence homology to any functional domain of CDK4.

44. Use according to claim 43 wherein the stracture of the crystalline fonn of a protein with significant amino acid sequence homology to any functional domain of CDK4 is solved using molecular replacement.

45. A method of treating a proliferative disorder, said method comprising administering to a subject in need thereof a compound of formula [1], [2], [6]-[9] as defined in claim 16, or a pharmaceutically acceptable salt thereof, in an amount sufficient to selectively inhibit CDK4 such that said proliferative disorder is treated.

46. A method of treating a CDK4 dependent disorder in a subject in need thereof, said method comprising administering to said subject a compound of formula [1], [2], [6]-[9] as defined in claim 16, or a pharmaceutically acceptable salt thereof, in an amount sufficient to selectively inhibit CDK4.

47. A method according to claim 46 wherein the CDK4 dependent disorder is a disorder associated with increased CDK4 activity.

48. A method according to claim 48 or claim 47 wherein the disorder is cancer.

49. A method of treating a proliferative disorder comprising selectively inhibiting CDK4 by administering to a subject in need thereof, a therapeutically effective amount of a compound of formula [1], [2], [6]-[9] as defined in claim 16, or a pharmaceutically acceptable salt thereof, such that treatment ofthe proliferative disorder occurs.

50. A method of selectively inhibiting CDK4 in a cell comprising contacting said cell with an amount of a compound of formula [1], [2], [6]-[9] as defined in claim 16, or a pharmaceutically acceptable salt thereof, such that CDK4 is selectively inhibited in said cell.

51. A method according to claim 53 or claim 55 wherein the cell is a cancer cell.

52. A fragment of CDK4, or a homologue, mutant, or derivative thereof, comprising a ligand binding domain, said ligand binding domain being defined by the amino acid residue structural coordinates selected from one or more of the following: V20, F93, D99, L147, El 44 and D158.

53. A fragment of CDK4, or a homologue, mutant or derivative thereof, according to claim 52 which conesponds to a portion ofthe stracture co-ordinates of Table 1.

54. Use of a fragment of CDK4, or a homologue, mutant, or derivative thereof, according to claim 52 or 53 in an assay for identifying candidate compounds capable of modulating CDK4.

55. A method of screening for a modulator of CDK4 substantially as described herein, and with reference to the accompanying drawings.

56. An assay substantially as described herein, and with reference to the accompanying drawings.

57. A CDK4 modulator substantially as described herein, and with reference to the accompanying drawings.

58. A process substantially as described herein, and with reference to the accompanying drawings.