EP1252311A2

EP1252311A2 - Water-soluble ligand-binding proteins of ligand-gated ion channels, crystals thereof and their use for screening ligands of ligand-gated ion channels

Info

Publication number: EP1252311A2
Application number: EP01909732A
Authority: EP
Inventors: August Benjamin Smit; Titia Karen Sixma
Original assignee: Stichting voor de Technische Wetenschappen STW
Current assignee: Stichting voor de Technische Wetenschappen STW
Priority date: 2000-02-10
Filing date: 2001-02-09
Publication date: 2002-10-30
Also published as: JP2003521932A; WO2001058951A2; IL151156A0; AU3737201A; WO2001058951A3; CA2331876A1

Abstract

Provided are water-soluble ligand-binding proteins derived from molluscs and analogs of ligand-gated ion channels, crystals thereof and their use for screening ligands of ligand-gated ion channels. In particular, water-soluble ligand-binding proteins are provided that are capable of forming multimers and are amenable to crystallization. The crystal structure of one of these proteins, an acetylcholine binding protein (AChBP) is provided, which can be used to generate 3D models of the extracellular ligand-binding domain of ligand-gated ion channels and thus for screening of drugs that act on these ion channels. Furthermore, chimeric proteins are provided that are capable of binding a ligand of a ligand-gated receptor, and comprising at least the amino acids of the AChBP determining solubility of the AChBP, in the same positions as in the AChBP, and furthermore comprising amino acids determining binding to said ligand.

Description

WATER-SOLUBLE LIGAND-BINDING PROTEINS AND ANALOGS OF LIGAND- GATED ION CHANNELS, CRYSTALS THEREOF AND THEIR USE FOR SCREENING LIGANDS OF LIGAND-GATED ION CHANNELS

SUMMARY OF THE INVENTION

Novel water-soluble ligand-binding proteins have been identified and isolated, which have a ligand-binding profile substantially similar to that of ligand-gated ion channels. DNA molecules encoding such proteins have been cloned and characterized. The biological and structural properties of these proteins are disclosed, as is the amino acid and nucleotide sequence. The recombinant DNA molecules, and portions thereof, are useful for isolating homologues of the DNA molecules, identifying and isolating genomic equivalents of the DNA molecules, and identifying, detecting or isolating mutant forms of the DNA molecules. Using a recombinant expression system functional DNA molecules encoding the water-soluble ligand-binding proteins as well as chimeras have been functionally produced. Furthermore, the water-soluble ligand-binding proteins could be crystallized revealing the three dimensional (3D) structure and enabling the modeling of the 3D structure of the ligand-binding domain of ligand-gated ion channels. The invention is further in the field of the development of new drugs that are capable of selectively intervening in neuronal signaling pathways. The invention is more in particular concerned with providing new analogues of the channel-coupled receptors, crystal structures thereof and to their use in screening ligands for these receptors.

Several documents are cited throughout the text of this specification either by name or are referred to by numerals within parenthesis. Full bibliographic citations may be found at the end of the specification immediately preceding the claims. Each of the documents cited herein (including any manufacturer's specifications, instructions, etc.) are hereby incorporated herein by reference; however, there is no admission that any document cited is indeed prior art as to the present invention. BACKGROUND OF THE INVENTION

The communication in the central nervous system (CNS) occurs through a complex interaction of electrical and chemical signals. Molecules bearing chemical information are called neurotransmitters. The chemical information is converted in electric currents on the post-synaptic membrane, which is specialised in recognising and binding neurotransmitters by means of protein receptors. The specific binding of a ligand to one type of such receptors, the ionotropic receptors, induces a fast opening of the ion channel coupled to the receptor. An important group of ionotropic receptors is the superfamily of the channel-coupled receptors, also referred to as ligand-gated receptors, including the 7-amino-butyric acid (GABA_A) receptor, the glycine receptor, the serotonin-3 (5-HT3) receptor and both neuronal and muscle-type nicotinic acetylcholine receptors (nAChR). These receptors share certain structural features such as (1) a 15-residue cysteine loop between amino acids 128 and 142 corresponding to the Torpedo AChR α unit, (2) four trans-membrane domains, (3) similar subunit arrangements, and (4) homologies in amino acid sequence. Activation of these receptors causes a change in electrical current and hyperpolarisation of the cell membrane and consequently an inhibition of the electrical activity of the cell. The GABA_A receptor and the glycine receptor are coupled to a chloride-selective channel, and thus the inhibition of the electrical activity leads to inhibition of the cell response. On the other hand, activation of the 5-HT3 receptor and the nAChRs provokes an excitatory response on the cell because they are connected to a cation-selective channel (Na+, K+, Ca2+). The AChRs are the best studied of the ligand-gated receptors; for a review, see Arias, Brain Research Reviews, 25 (1997)133-191 and Arias, Neurochem. Int. 36 (2000), 595-645). Mutations in these ligand-gated ion- channels (LGICs) lead to diseases such as congenital myasthenia gravis, epilepsy, startle syndrome and alcohol sensitivity (Vafa and Schofield, Int. Rev. Neurobiol. 42, 285-332; 1998). NAChRs mediate nicotine addiction in chronic tobacco users. Since nicotine binding to these receptors also has a positive effect on Alzheimer's disease, Parkinson's disease and schizophrenia these receptors present an important drug target (Paterson and Nordberg, A. Neuronal nicotinic receptors in the human brain. Prog. Neurobiol. 61 , 75-111 ; 2000).

The development of new active compounds that can selectively or - as the case may be - a-selectively bind to the channel-coupled receptors, is of utmost importance for the understanding of the processes occurring in the nervous system and for the treatment of disturbances of neural conditions. The development of such active compounds requires the availability of a reliable model system for the corresponding receptors. The primary structural features (amino acid sequences) of the various receptors have been largely elucidated by now. Certain subunits of the AChRs have been found to be determinant in the pharmacological specificity or affinity of the receptor for its ligand (Corringer et al., J. Neuroscience 18 (1998), 648-657).

However, the study of the ligand binding properties of the receptor proteins is hampered by the fact that the spatial structure of the proteins - which is decisive in the binding of ligands - is still unknown. This is partly because crystallisation of the receptor proteins has been unsuccessful up to now.

The above-defined technical problem is solved by the present invention by providing the embodiments characterized in the claims. Accordingly, in one aspect the present invention relates to a water-soluble protein derived from a mollusc being capable of binding a ligand of a ligand-gated receptor.

It has been found according to the invention that acetylcholine-binding proteins (AChBP) of certain molluscs show a surprising structural similarity with the channel- coupled receptors on the one hand and have interesting physical properties, such as water-solubility, on the other hand. The molluscan AChBPs are capable of forming multimers, especially pentamers, and of binding specific toxins such as α- bungarotoxin. These multimers may be homogeneous (identical units) or heterogeneous (different units). These properties make them eminently suitable as model systems for studying the binding of candidate ligands to the channel-coupled receptors. It has been possible to produce these molluscan AChBPs in recombinant systems, thus allowing convenient and large-scale production thereof. Moreover, it is feasible to construct hybrid proteins sharing the physical properties of the mollusc AChBP with the pharmacological properties of the (human) channel-coupled receptors, thus providing new dedicated tools for screening ligands for these receptors.

The AChBP is a naturally occurring analogue of the extracellular domains of the α- subunits of the neuronal nicotinic acetylcholine receptors (nAChRs). In contrast to the nAChRs, it lacks domains to form a transmembrane ion channel, but alike the nAChRs it assembles into a homo-pentamer (Figure 6). Moreover, AChBP has ligand-binding characteristics that are typical for a nicotinic receptor. The 3- dimensional structure of AChBP was solved by X-ray crystallography at 2.7A resolution (current Rf_aGtor = 27.9 %, R_free = 30.0 %). In crystals, as in solution, AChBP forms a stable homo-pentamer with dimensions comparable to those of the ligand- binding domain of the nAChR, as determined in EM studies by Unwin, Struct. Struct. Biol 21 (1998), 181-190. The high-resolution crystal structure of AChBP, along with biochemical and pharmacological data, supports the extrapolation of AChBP as a good mimic of ligand-binding domains of ligand-gated ion channels including nAChR,

5-HT3R, GABA_A,cR and GlyR.

Four AChBPs according to the present invention are exemplified herein, isolated and cloned from the CNS of Lymnaea stagnalis (L-AChBP_T1 and L-AChBP_T2) and

Bulinus truncatus (B-AChBP_T1 and B-AChBP_T2). L-AChBP_T1 and 2 are 229 amino acid proteins with a signal sequence of 19 amino acids (224 and 21 amino acids, respectively, for B-AChBP_T1 and 2; see also Figure 1) and have sequence homology with the extracellular domains of the subunits of ligand-gated ion channels (Figure 3), in particular with those of the nAChRs (Figure 4 and 5). The mass of the purified AChBP from Lymnaea has been determined by mass-spectrometry. The glycosylated form has a mass of about 24720 Da and the de-glycosylated form of about 23832 Da. In SDS-PAGE the glycosylated AChBP migrates between the 14 and 26 kDA marker proteins. Hydrophopicity plots of the AChBPs are shown in Figure 2, which reveal those regions of the ligand-binding proteins that are particularly hydrophilic and thus may be replaced at least in part or essential amino acids thereof in the ligand-binding domain of the ligand-gated ion channel. Sequence conservation is particularly high in the so-called loop areas (reviewed by Arias, Neurochem. Int. 36 (2000), 595-645), which contain the residues involved in ligand- binding. The cysteine residues characteristic for the Cys-loop family of ligand gated receptors are conserved in AChBP. Also the double cysteine typically found in the alpha subunits of the nAChR is present. AChBP protein sequence ends at the position where in the nAChRs the first predicted transmembrane domain would start. The ligand-binding characteristics of AChPBs are described in Example 4 and summerized in Table 2.

The terms "channel coupled receptors", "ligand-gated receptor", "ligand-gated ion channel" are used interchangeable herein. However, in context with the natural occurring, in particular human molecules the term "ligand-gated ion channel" is preferably used. The water-soluble ligand-binding protein of the invention can also be characterized as a ligand-binding protein having at least 10%, more preferably at least 12%, still more preferably at least 15% and most preferably at least 20% amino acid sequence identity to a vertebrate ligand-gated ion channel but missing any trans-membrane domain. A ligand-gated receptor of the present invention is characterized by having substantially the same ligand-binding characteristics of a vertebrate, preferably mammalian, most preferably human ligand-gated ion channel but comprising at least one alteration in the original amino acid sequence, said alteration resulting in the presence of an amino acid determining or contributing to the water-solubility of the water-soluble ligand-protein found in molluscs, in particular snails such as those described in more detail below.

The terms "ligand-binding protein", "ligand-binding domain" and "ligand-binding receptor" are meant to at least include the portion of a water-soluble ligand-binding protein or corresponding modified ligand-gated ion channel required for binding a ligand. Minimally the ligand-binding domain consists of a peptide containing that domain. However the use of this term is meant to include a ligand- binding domain or protein that is comprised by a larger portion of, for example, ligand-gated ion channel, such as a fully reconstituted nicotinic acetylcholine receptor.

As shown in Figure 3 the nicotinic acetylcholine receptor (nAChR) belongs to a well- understood member of the ligand-gated ion channels superfamily. The members of this signaling protein group, including 5-HT3, glycine, GABA_A, and GABA_C receptors, are thought to share common secondary, tertiary, and quaternary structures on the basis of a high degree of sequence similarity. Therefore, it is expected that the novel findings in respect to the exemplified AChBP equally apply to the other members of the mentioned ligand-gated ion channels superfamily. Thus, either water-soluble protein being capable of binding a ligand of any of those ligand-gated ion channels may be found in molluscs or the present 5-HT3, GABA_A, and glycine receptors can be modified such as to substantially retain their binding affinity. Accordingly, the ligand of the water-soluble ligand-binding protein is preferably acetylcholine, gamma-amino-butyric acid (GABA), glycine, nicotine or serotonin. Isolation of such water-soluble ligand-binding proteins can be done as described in Example 1 for the AChBP of the present invention. Instead of α-bungarotoxin other known ligands or can be used for affinity purification. Most preferably, water-soluble ligand-binding protein of the invention is a acetylcholine-binding protein (AChBP). Preferably, the ligand-binding protein displays substantially the binding characteristics shown in Table 2.

The acetylcholine-binding proteins to be used according to the invention are originally derived from aquatic molluscan species, especially species from the class of the snails (Gastropoda), in particular from the order of the lunged snails (Pulmonata). The order of the Pulmonata is divided into the suborders of the Basommatophora (mostly aquatic snails), Systellommatophora and Stylommatophora (mostly land snails). The Basommatophora include the families of the Acroloxidae (e.g. genus Acroloxus), Lymnaeidae (e.g. genera Galba, Stagnicola, Radix and Lymnaea), Physidae (e.g. genera Physa and Aplexa) and Planorbidae (e.g. genera Planorbis,

Anisus, Ancylus, Gyraulus, Biomphalaria and Bulinus). Examples of suitable species are Lymnaea stagnalis (pond snail) and Bulinus truncatus. The isolation of the

AChBPs from these snails, cloning of the cDNA encoding these AChBPs and their characterization including the full amino acid sequences is described in the examples. The cDNA and amino acid sequences of the AChBPs of Lymnaea stagnalis ate depicted in SEQ ID Nos. 1 and 2 (L-AChBP__T1 ) and SEQ ID Nos. 3 and 4 (L-AChBP_T2). Those of Bulinus truncatus are depicted in SEQ ID Nos. 5 and

6 (B-AChBP_T1) and SEQ ID Nos. 7 and 8 (B-AChBP_T2). Features of these proteins are further described in the examples and the accompanying figures.

While a water-soluble ligand-binding protein derived form a Pulmonata species, preferably from a Basommatophora species is preferred, it will be appreciated that the present invention generally relates to any water-soluble protein being capable of binding a ligand of a ligand-gated receptor comprising an amino acid sequence selected from the group consisting of:

(a) an amino acid sequence as depicted in any one of SEQ ID Nos. 2, 4, 6 or 8 or a functional equivalent thereof, or a fragment of at least 5 continuous amino acids thereof; (b) an amino acid sequence having at least 30% amino acid identity to the amino acid sequence of any one of SEQ ID Nos. 2, 4, 6 or 8; and (c) an amino acid sequence resulting in a protein which is detectable by a monoclonal or polyclonal antibody which recognises, preferably with a binding affinity of at least 10^"7M, a protein comprising an amino acid sequence of (a) or (b).

Identity or similarity, as known in the art, are relationships between two or more polypeptide sequences or two or more polynucleotide sequences, as determined by comparing the sequences. In the art, identity also means the degree of sequence relatedness between polypeptide or polynucleotide sequences, as the case may be, as determined by the match between strings of such sequences. Both identity and similarity can be readily calculated (Computational Molecular Biology, Lesk, ed., Oxford University Press, New York, 1988; Biocomputing: Informatics and Genome Projects, Smith, ed., Academic Press, New York, 1993; Computer Analysis of Sequence Data, Part I, Griffin and Griffin, eds., Humana Press, New Jersey, 1994; Sequence Analysis in Molecular Biology, von Heinje, Academic Press, 1987; and Sequence Analysis Primer, Gribskov and Devereux, eds., M Stockton Press, New York, 1991 ). While there exist a number of methods to measure identity and similarity between two polynucleotide or two polypeptide sequences, both terms are well known to skilled artisans (von Heinje, supra; Gribskov and Devereux, supra; and

Carillo and Lipman SIAM J. Applied Math. 48 (1988), 1073). Methods commonly employed to determine identity or similarity between sequences include, but are not limited to those disclosed in Carillo and Lipman; see supra. Preferred methods to determine identity are designed to give the largest match between the sequences tested. Methods to determine identity and similarity are codified in computer programs. Preferred computer program methods to determine identity and similarity between two sequences include, but are not limited to, GCG program package

(Devereux et al., Nucleic Acids Research 12 (1984), 387), BLASTP, BLASTN, psi

BLAST and FASTA (Atschul et al., J. Molec. Biol. 215 (1990), 403).

In another embodiment, the present invention relates to a water-soluble protein being capable of binding a ligand of a ligand-gated receptor comprising

(a) at least the amino acids of the water-soluble protein described above determining solubility of said protein, in the same or corresponding positions as in said protein; and

(b) at least 4 amino acids determining binding to said ligand.

Protein expression studies have shown that wild-type AChBP of the mollusc Lymnaea stagnalis can be produced in Pichia pastoris yeast. The yeast cells express AChBP in a homopentameric form and secrete the protein complex into the medium. The large amounts of AChBP per volume of medium produced (up to 2 mg per liter medium) and the large volumes of yeast that can be cultured allow a large-scale production of AChBP. Besides the wild-type AChBP, various AChBP mutants have been produced in Pichia pastoris. These include mutants containing the following single point mutations (the numbers refer to the amino acid position in the AChBP sequence of Lymnaea stagnalis depicted in SEQ ID No. 2 counted from the first amino acid of the signal peptide; the letter before the number indicates the original amino acid and the letter after the number indicates the mutant amino acid) N85D, H164Y, D194N, Y204P, Y211 P and D213N.

Thus the invention pertains to water-soluble proteins derived from molluscan, preferably acetylcholine binding proteins (AChBP's), which are capable of forming multimers, and are capable of binding a ligand of a ligand-gated receptor. These proteins comprise, on the one hand, at least of the amino acids of the AChBP determining solubility of the AChBP in the same positions as in the AChBP, and, on the other hand, amino acids determining binding to the ligand of the ligand-gated receptor. The degree of identity with the molluscan AChBP sequence can be defined by amino acid identity, of at least 15%, preferably 20%, more preferably 30%, still more preferably 40%, preferably at least 50 or even at least 60%, preferably more than 70%, more preferably more than 80% and most preferably at least 90% identity, or more, as determined, e.g., using the art-known BLAST algorithm. The amino acids determining binding to the ligand should comprise at least 4 amino acids, preferably at least 6 or even at least 8 amino acids, including a series of at least 3 or 4 amino acids, corresponding to the receptor sequence and preferably differing from the corresponding AChBP amino acids. Preferred embodiments of these proteins are further defined below. Usually, the water-soluble ligand-binding protein or domain as part of a for example chimeric ligand-gated ion channel will comprise 200-240 amino acids. The ligand is preferably acetylcholine, nicotine, lophotoxin, d-tubocurarine, carbamylcholine, galanthamine or epibatidine. Said ligand-gated receptor can be derived from an arthropod (preferably insect), a plant (preferably a higher plant, most preferably a seed plant) or a chordate (preferably a mammalian, most preferably human), preferably said ligand-gated receptor is a nicotinic acetylcholine receptor.

Usually, the said amino acids in the water-soluble ligand-binding proteins of the invention, which determine solubility are in the same positions as in the AChBP having the amino acid sequence as depicted in any one of SEQ ID Nos. 2, 4, 6 or 8. The solubility determining regions are based on solvent accessibility in structure. The respective amino acid residues can be chosen for example according to Figure 10 or 1 1 in which the solvent accessible regions are indicated. Preferably, the water- soluble ligand-binding protein of the invention comprises an amino acid sequence having at least 40% amino acid identity to the amino acid sequence of the mature AChBP comprising the amino acid sequence of any one of SEQ ID Nos. 2, 4, 6 or 8, in which the ligand binding amino acids have been replaced with the corresponding amino acids of a ligand-gated receptor.

In one embodiment of the protein of the invention said solubility-determining amino acids (a) comprise hydrophilic amino acids (Asp, Glu, Arg, Lys) from the sequences 20-44, 73-81 , 86-92, 112-120, 135-152, 166-189, 196-20, 209-213, and/or 219-227 of SEQ ID No. 2. The amino acid sequences of L-AChBP_T1 (SEQ ID No. 2) and T2 (SEQ ID No. 4) are almost similar. For the sake of clarity, reference is always made to L-AChBP_T1 (SEQ ID No. 2). However, all references to amino acid residues within are valid for both T1 and T2, with the noticeable exceptions of Arg(167) becoming Gly(167) and and Thr(203) becoming lle(203). Furthermore, regarding the amino acid residues

(domains) from L-AChBP_T1 and the corresponding residues from B-AChBP the following list provide those amino acid positions in which L-AChBP and B-AChBP differ. All amino acid residue numbers below correspond to their position within the amino acid sequence of the immature protein (numbering starting at methionine (1).

One could also start numbering at the start of the amino acid sequence of the mature sequence (L(1 )DRAD for L-AChBP and Q(1)IRW for B-AChBP). When using this second method (1 st amino acid of the mature seq. = position 1 ) simply subtract 19 from the L-AChBP position numbers and 21 from the B-AChBP position numbers, for example Asp(36) becomes Asp(17) for L-AChBP) and Asp(15) for B-AChBP. For the further embodiments the positions are given for L-AChBP T1 (SEQ ID No. 2) followed by an indication of the corresponding amino acid positions in the amino acid sequence of L-AChBP_T2 (SEQ ID No. 4) and B-AChBP_T1 (SEQ ID No. 6) & B- AChBP_T2 (SEQ ID No. 8) in the form of (L-AChBP_T1 &T2 : B-AChBP_T1 &T2).

In a preferred embodiment said solubility determining amino acids (a) comprise amino acids Asp(36), Asp(68), Glu(115), Arg(137), Asp(143), Asp(148), Glu(150), Arg(167), Arg(189), Glu(215) of SEQ ID No.2, wherein Asp may be exchanged for Glu and vice versa and Lys may be exchanged for Arg and vice versa (L- AChBP_T1&T2 : B-AChBP_T1&T2; Asp(36) : Asp(36); Asp(68): Asp(68); Glu(115) Glu(1 16); Arg(137): Arg(138); Asp(143): Asp(144); Asp(148): Asp(149); Glu(150) Glu(151); Arg(167): Gly(167), in L-AChBP_T2 : Lys(168); Arg(189): Lys(190) GIu(215): Glu(216).

In a still more preferred embodiment the water-soluble ligand-binding protein comprises the amino acids Cys(142), Thr(149), Ala(153). Thr(154), Cys(155), Arg(156), lle(157) and/or Lys(158) of SEQ ID No. 2. (L-AChBP_T1 &T2 : B- AChBP_T1 &T2; Cys(142): Cys(143); Thr(149): Thr(150); Ala(153): Ala(154); Thr(154): Thr(155); Cys(155): Cys(156); Arg(156): Arg(157); lle(157): lle(158); Lys(158): Lys(159). In a further embodiment the water-soluble ligand-binding protein comprises either in addition or alternatively the amino acids (b) Pro(39), Trp(77), Trp(101 ), Pro(103), Asp(194), and/or Ser(161) of SEQ ID No. 2 (L-AChBP_T1 &T2 : B-AChBP_T1&T2; Pro(39): Pro(39); Trp(77): Trp(77); Trp(101 ): Trp(102); Pro(103): Pro(104); Ser(161 ): Ser(162); Asp(194): Ser(195).

In a still further embodiment the water-soluble ligand-binding protein comprises either in addition or alternatively to the above described embodiments amino acid sequences 165-169 and/or 200-203 of SEQ ID No. 2 have been exchanged with the corresponding sequence of the ligand-gated receptor (L-AChBP_T1&T2 : B-

AChBP_T1 &T2; His(165)-lso(169): , Asp(166)-Phe(170) (B-AChBP_T1) : Asp(166)- Leu(170) (B-AChBP_T2); Asn(200)-Thr(203); lso(203) for L-AChBP_T2: Asn(201)-

Lys(204).

The amino acids determining binding to the ligand of the nicotinic acetylcholine receptor include three stretches on the nAChR alpha subunits. These stretches contain amino acids that are conserved throughout the various nAChR alpha subunits and that are essential for ligand binding. These stretches (corresponding to the Torpedo alpha subunit) are (numbering of nAChR α7 as depicted in SEQ ID No. 9): Trp (108) - Tyr (115), Trp (108) and Tyr ( 15) being essential; Trp (171) - Tyr (173), the amino acids Trp (171) and Tyr (173) being essential; Tyr (210) - Tyr (217), the amino acids Tyr (210), Cys (212), Cys (213) and Tyr (217) being essential. In the chimeric proteins according to the invention, at least the essential amino acids of at least one of these stretches haven been substituted for the corresponding amino acids. Preferably, the entire stretches have been substituted.

In a particularly preferred embodiment of the invention, the water-soluble ligand- binding protein is capable of binding a ligand of an acetylcholine receptor, wherein in said protein at least one of the amino acid sequences Trp(101 ) - Tyr(T108), Trp(162) - His(164) and Tyr(204) - Tyr(21 1 ) of SEQ ID No. 2 has been exchanged with the corresponding sequence of the acetylcholine receptor (L-AChBP_T1&T2 : B- AChBP_T1 &T2; Trp(101 )-Tyr(108): Trp(102)-Tyr(109); Trp(162)-His(164): Trp(163)- His(165), (B-AChBP_T1 ) : Trp(163)-Phe(165) (B-AChBP_T2); Tyr(204)-Tyr(211 ): Tyr(205)-Tyr(212).

On the basis of homology to the AChBPs, it is possible to change amino acid residues in the original amino acid sequence of the ligand-gated ion channel, which are not critical to ligand-binding or essential for the tertiary and quaternary structure of the receptor but could be substituted to amino acid residues which according to the AChBP in particular the crystal structure contributes to their water-solubility. As a result the ligand-gated ion channel or its ligand-binding domain or the respective monomers and pentamers are for example expected to be more easily expressible in recombinant expression system and more importantly amenable to crystallization, allowing the construction of three-dimensional models of their ligand binding domains. Thus, in another embodiment the present invention relates to a method for the production of a water-soluble ligand-gated receptor or a corresponding ligand-binding domain or for improving the water solubility and accessibility to crystallization of such a receptor or domain, said method comprising altering the amino acid sequence of the extracellular domain of a ligand-gated receptor by way of substituting, adding, deleting or modifying at least one amino acid at a position corresponding to an amino acid determining or contributing to the water-solubility of the above-described water- soluble ligand-binding protein of the present invention The method of the invention can be performed using conventional techniques known in the art, for example, by using amino acid deletion(s), insertion(s), substitution(s), addition(s), and/or recombination(s) and/or any other modification (s) known in the art either alone or in combination. Methods for introducing such modifications in the DNA sequence underlying the amino acid sequence of the ligand-binding domain a ligand-gated ion channel are well known to the person skilled in the art; see, e.g., Sambrook, Molecular Cloning A Laboratory Manual, Cold Spring Harbor Laboratory (1989) N.Y. The resulting ligand-gated receptor or ligand-binding domain retains comparable in vitro and preferably also in vivo ligand-binding activity to that of the ligand-gated ion ^' channel, and more importantly, allow complete crystallization of the protein such that they may be characterized by X-ray crystallography. The X-ray crystallographic data can be used for example for identification and construction of possible therapeutic compounds in the treatment of various disease conditions.

As has- been discussed herein before, the ligand-gated ion channel superfamily including nACh, 5-HT3, glycine, GABA_A, and GABA_G receptors as well as invertebrate glutamate ion-channels and MOD-1 serotonin channel contain extracellular ligand binding domains that are homologous to the AChBP. Many of these receptors are promising drug targets. Therefore, the ligand-gated receptor to be modified is preferably one of those of the mentioned superfamily, most preferably it is nAChR. Information on the nucleotide and amino acid sequences, structural elements, functional assays of the nAch, 5-HT3, glycine, GABA_A, and GABA_C receptors can be found in the prior art. For example, the nicotinic receptors at the amino acid level are described in Corringer et al., Annu. Rev. Pharmacol. Toxicol. 40 (2000), 431 -458. Means for retrieving nucleotide and amino acid sequences, performing sequence alignments in order to identify the most likely critical amino acid residues are described below and in the examples; for further general information see the review on periplasmic binding protein (PBP), an ancient protein module present in multiple drug receptors by Felder et al., PharmSci. 1 (2) (1999). In a preferred embodiment of the method of the present invention, said at least one amino acid is altered to the corresponding amino acid of the amino acid sequence depicted in any one of SEQ ID Nos. 2, 4, 6 or 8, or to a an equivalent amino acid, preferably in which said solubility-determining amino acids comprise solvent accessible regions in the crystal structure according to Figure 10 or 1 1. Preferred amino acid sequence positions and amino acid substitutions are described above for the AChBP and can be applied generally in the method of the present invention. It is expected that the insertion of the loop Cys123-Cys136 of the mature AChBP SEQ ID No. 2 into the equivalent region (Cys127-Cys141 ) in the mature nicotinic α7 homopentamer ligand binding domain creates an easily expressed form of this protein. Likewise, this loop or an equivalent loop from other water-soluble ligand proteins of the present invention can be inserted into the equivalent region of other homopentamehc ligand binding domains of ligand gated ion channels such as the glycine receptor and the 5-HT3 receptor to create an easily expressed form of those proteins.

Thus, in one embodiment, the present invention relates to any one of the above described methods, wherein loop Cys123-Cys136 of SEQ ID No. 2 is inserted into the corresponding region of the ligand binding domain of the ligand-gated receptor.

The above described water-soluble ligand-gated receptor or a corresponding ligand- binding domain are usually prepared by site-directed mutagenesis of the underlying encoding polynucleotide. Once the corresponding polynucleotide has been generated it can be used to express the altered ligand-gated receptor or a corresponding ligand-binding domain. Thus, the method of the present invention commonly comprises (a) culturing a host cell transfected with and capable of expressing a polynucleotide comprising a nucleotide sequence encoding the altered amino acid sequence; and optionally (b) recovering said water-soluble ligand-gated receptor or corresponding ligand-binding domain from the culture. Methods for the expression and purification of the water-soluble ligand-gated receptor or corresponding ligand-binding domain of the present invention are described further below. Preferably, the expression system described in Examples 4 and 5, or corresponding expression systems are used. The present invention also relates to the a water-soluble ligand-gated receptor and ligand-binding domain obtainable by the above described methods of the invention. Preferably, said water-soluble ligand-gated receptor exhibits a 10-fold, more preferably 100-fold, still more preferably 1000-fold and most preferably 10000-fold higher solubility in water than the corresponding wild type, preferably human ligand- gated receptor. However, improvements in water solubility of about 2 to 5 fold is also already advantageous. The average hydrophobicity may be in the range of -100 to - 400. Accordingly, the present invention provides methods for the prediction and creation of mutants and chimeras of ligand binding domains of homopentameric acetylcholine receptor subtypes and of other homopentameric ion channels with increased solubility.

In one embodiment the water-soluble ligand-binding protein of the invention further comprises a spacer sequence allowing coupling with a carrier body. The spacer sequence may be an amino acid sequence encodable by a polynucleotide or other molecule such as polymethylene anchor groups commonly used in chip technology. The chimeric protein of the invention may further comprise a spacer sequence, which allows coupling of the protein to a carrier body. Such spacer sequence may be e.g. an oϋgo-histidine stretch attached to the C-terminus of the protein. Such an oligo- histidine stretch is capable of binding to Talon© metal affinity beads or similar carriers. Such binding stretches have no detectable influence on the pharmacological properties of the proteins. The chimeric proteins according to the invention can be used for screening of specific binding of potential drugs, in particular screening for modulators of ion-channel opening. Conventional in vitro screening techniques, such as phage display technology, can be used for this purpose. High-throughput assays, possibly in combination with combinatorial chemistry can also be used. Specific binding of test compounds to the (immobilised) chimeric proteins of the invention can be performed e.g. by competition binding assays using alpha bungarotoxin as a competitor. The invention also concerns test kits containing the proteins described above, together with further means for carrying out a screening test, such as carriers, labels, diluents, other chemicals etc.

In addition, the present invention relates to fusion proteins comprising the water- soluble ligand-binding protein of the invention or a binding fragment thereof and a fragment of a ligand-gated receptor. The term "fusion protein" as used herein refers to protein constructs that are the result of combining multiple protein domains or linker regions for the purpose of gaining the combined functions of the domains or linker regions. This is may be accomplished by molecular cloning of the nucleotide sequences encoding such domains to produce a new polynucleotide sequence that encodes the desired fusion protein. Alternatively, creation of a fusion protein may be accomplished by chemically joining two proteins. A fusion protein of the present invention preferably comprises at least the ligand-binding domain of the AChBP or of a ligand-gated ion channel, which has been modified in accordance with the above described methods.

Nicotinic acetylcholine receptors are ^■ comprised of five subunits, selected from a related family of subunit proteins. The neuronal subunits fall into two main types depending on the presence or absence of a pair of vicinal cysteines close to the binding site for acetylcholine. Thus all α-subunits contain paired cysteine residues thought to play a role in binding of nicotinic agonists (Aplin and Wonnacott, 48 (1994), 473-477), whereas the β-subunits do not. There are ten known alpha subunits, α1 to α10, and at least four beta subunits, β1 to β4. Receptors comprise at least one alpha subunit which in some cell types combine with a beta subunit and in some cases a gamma, delta and epsilon subunit. For example, the AChR at the neuromuscular junction is believed to have an (α1 )2β1γδ stoichiometry. Within the group of α- subunits there is marked diversity in the manner in which a complete functional nAChR is formed. The majority of the α subunits only form functional receptors when combined as a heteropentamer with β-subunits in the CNS (McGehee and Role, Annual Review of Physiology 57 (1995), 521 -546). However, α7, α8 and α9 nAChR subunits and the related 5-HT3A subunit are capable of forming functional homopentameric receptors. In this respect it is interesting that the phylogenetic relationship between nAChR subunits suggest that α7, α8, α9 and the related 5-HT3A subunit are more related to each other than to the subunits which only form heteropentameric receptors. Sequence homologies indicate that the α7, α8 and α9 subunits form a distinct subgroup of the alpha subunits. As is evident form the foregoing, the above described water-soluble ligand-binding protein or receptor or ligand-binding domain thereof can be used for forming complexes of homo- or heteromultimers, such as a dimer, pentamer or decamer consisting of at least one monomer of the mentioned proteins of the present invention. Preferably, these multimers constitute a function ligand-gated receptor. Preferably, said ligand-gated receptor is related to the nAchR.

The present invention also relates to the production of synthetic heteropentamers resembling heteropentameric gated ion-channels by mutation of AChBP, using knowledge of the crystal structure about the primary and secondary contact regions; see infra. Preferably, said synthetic heteropentamers resembles a heteropentameric nicotinic acetylcholine receptor. Accordingly, the present invention more generally relates to a ligand-gated ion channel comprising any one of the above described water-soluble ligand-binding proteins or receptors of the invention as a monomer, homo- or heterodimer or -pentamer. This method therefore allows the prediction and creation of mutants and chimeras of nicotinic acetylcholine receptors and other ligand-gated ion channels that are insensitive or more sensitive to toxin binding, e.g. bungarotoxin, lophotoxin, conotoxin, and other toxins that inhibit ligand-gated ion channels. Preferably, said ligand-gated ion channel is less or more sensitive to binding of toxins such as bungarotoxin, lophotoxin or conotoxin compared to the wild type ligand-gated ion channel.

Further information and examples how to create chimeric ligand-binding proteins in accordance with the present invention is given in Example 10.

The nucleotide and amino acid sequences of the acetylcholine, 5-HT3, glycine, GABA_A, and GABA_C receptors can be easily retrieved from public database, for example from the internet using http://www.ncbi.nlm.nih.gov/Entrez. The citations also include a reference to the corresponding publication also reporting on the functional expression of the respective receptor.

The use of recombinant acetylcholine-gated ion channels and functionally assays in the discovery of putative novel ligands has been described in Cosford, Pharm. Acta Helv. (2000), 74(2-3), 125-130. Furthermore, the cell-free expression and functional reconstitution of homo-oligome c al nicotinic acetylcholine receptors into planar lipid bilayers has been reported by Lyford and Rosenberg, J. Biol. Chem. (1999), 274(36), 25675-25681. The use of functional assays of cloned and native muscarinic acetylcholine receptors for determining the selectivity profile of toxins has been described by Olianas et al. (J. Pharmacol. Exp. Ther. 288 (1999), 164-170). A system for the evaluation of pharmacological differences and similarities between 5-HT3 receptors stably transfected cells is provided by for example Bruss et al., Naunyn- Schmiedebergs Archives of Pharmacology 360 (1999), 225-33. The primary structure and functional expression of the 5-HT3 receptor is described in Maricq et al., Science 254 (1991), 432-437. Likewise, the stable expression of human glycine α1 and α2 receptor monomers in mouse L(tk-) cells and their use for the study of the physiology and pharmacology of functional glycine receptors is described in Wick et al., J. Neurosci. Methods 87 (1999), 97-103. An example for the measurement of the pharmacology of recombinant GABA_A receptor subtypes is described in Simpson et al., J. Neurosci. Methods 99 (2000), 91-100. Further examples for assay systems are given below.

The described methods as well as others known to the person skilled in the art can be used for example to

(1 ) express and characterise the water-soluble ligand-binding proteins and ligand- gated ion channels of the present invention; and

(2) use stably transfected cells expressing the above described ligand-gated ion channels for the identification of novel ligands.

The present invention also relates to polynucleotides encoding the water-soluble ligand-binding proteins and ligand-gated ion channels of the present invention, and multimers thereof, preferably dimers or pentamers. Such polynucleotide may be a DNA such as a cDNA, or an RNA such as mRNA or any other form of nucleic acid including synthetic or modified derivatives and may encode the polypeptide in a continuous sequence or in a number of sequences interrupted by intervening sequences. In which ever form it is present, the polynucleotide is an isolated polynucleotide in that it is removed from its naturally-occurring state. This aspect of the invention is based on the cloning of the cDNA for ligand-binding proteins. In a preferred embodiment, the polynucleotide comprises the nucleotide sequence of any one of SEQ ID Nos. 1 , 3, 5 or 7, optionally including one or more mutations or deletions which do not substantially affect the activity of the polypeptide encoded thereby. Such mutations include those arising from the degeneracy of the genetic code, as well as those giving rise to any of the amino acid mutations or deletions discussed above. The polynucleotides of the invention preferably comprise

(a) a nucleotide sequence having at least 15 continuous nucleotides of the nucleotide sequence depicted in any one of SEQ ID Nos. 1 , 3, 5 or 7 or a degenerated nucleotide sequence thereof; or

(b) a nucleotide sequence capable of hybridizing to a nucleotide sequence of (a) under stringent hybridisation conditions.

Typically, selective hybridization will occur when there is at least about 55% sequence identity ~ preferably at least about 65%, more preferably at least about 75%, and most preferably at least about 90% ~ over a stretch of at least about 14 nucleotides; see, e.g., Kanehisa, Nucleic Acids Res. 12 (1984), 203-213, herein incorporated by reference. Nucleic acid hybridization will be affected by such conditions as salt concentration, temperature, solvents, the base composition of the hybridizing species, length of the complementary regions, and the number of nucleotide base mismatches between the hybridizing nucleic acids, as will be readily appreciated by those skilled in the art.

"Stringent hybridization conditions" and "stringent wash conditions" in the context of nucleic acid hybridization experiments depend upon a number of different physical parameters. The most important parameters include temperature of hybridization, base composition of the nucleic acids, salt concentration and length of the nucleic acid. One having ordinary skill in the art knows how to vary these parameters to achieve a particular stringency of hybridization. In general, "stringent hybridization" is performed at about 25°C below the thermal melting point (T m) for the specific DNA hybrid under a particular set of conditions.

"Stringent washing" is performed at temperatures about 5°C lower than the Tm for the specific DNA hybrid under a particular set of conditions. The Tm is the temperature at which 50% of the target sequence hybridizes to a perfectly matched probe; see Sambrook et al., page 9.51 , hereby incorporated by reference. The Tm for a particular DNA-DNA hybrid can be estimated by the formula: Tm = 81.5°C + 16.6 (log10[Na+ ]) + 0.41 (fraction G + C) - 0.63 (% formamide) - (600/I) where I is the length of the hybrid in base pairs. The Tm for a particular RNA-RNA hybrid can be estimated by the formula: Tm = 79.8°C + 18.5 (logl 0[Na+ ]) + 0.58 (fraction G + C) + 11.8 (fraction G + C)2 - 0.35 (% formamide) - (820/I).

The Tm for a particular RNA-DNA hybrid can be estimated by the formula: Tm = 79.8°C + 18.5(log10[Na+ ]) + 0.58 (fraction G + C) + 11.8 (fraction G + C)2 - 0.50 (% formamide) - (820/I). In general, the Tm decreases by 1 -1.5°C for each 1 % of mismatch between two nucleic acid sequences. Thus, one having ordinary skill in the art can alter hybridization and/or washing conditions to obtain sequences that have higher or lower degrees of sequence identity to the target nucleic acid. For instance, to obtain hybridizing nucleic acids that contain up to 10% mismatch from the target nucleic acid sequence, 10-15°C would be subtracted from the calculated Tm of a perfectly matched hybrid, and then the hybridization and washing temperatures adjusted accordingly. Probe sequences may also hybridize specifically to duplex DNA under certain conditions to form triplex or other higher order DNA complexes. The preparation of such probes and suitable hybridization conditions are well known in the art. An example of stringent hybridization conditions for hybridization of complementary nucleic acid sequences having more than 100 complementary residues on a filter in a Southern or Northern blot or for screening a library is 50% formamide/6X SSC at 42°C for at least ten hours. Another example of stringent hybridization conditions is 6X SSC at 68°C for at least ten hours. An example of low stringency hybridization conditions for hybridization of complementary nucleic acid sequences having more than 100 complementary residues on a filter in a Southern or northern blot or for screening a library is 6X SSC at 42°C for at least ten hours.

Hybridization conditions to identify nucleic acid sequences that are similar but not identical can be identified by experimentally changing the hybridization temperature from 68°C to 42°C while keeping the salt concentration constant (6X SSC), or keeping the hybridization temperature and salt concentration constant (e.g. 42°C and 6X SSC) and varying the formamide concentration from 50% to 0%. Hybridization buffers may also include blocking agents to lower background. These agents are well-known in the art; see Sambrook et al., pages 8.46 and 9.46-9.58, herein incorporated by reference. Wash conditions also can be altered to change stringency conditions. An example of stringent wash conditions is a 0.2x SSC wash at 65°C for 15 minutes (see Sambrook et al., for SSC buffer). Often the high stringency wash is preceded by a low stringency wash to remove excess probe. An exemplary medium stringency wash for duplex DNA of more than 100 base pairs is 1x SSC at 45°C for 15 minutes. An exemplary low stringency wash for such a duplex is 4x SSC at 40°C for 15 minutes. In general, signal-to-noise ratio of 2x or higher than that observed for an unrelated probe in the particular hybridization assay indicates detection of a specific hybridization.

By the provision of the nucleotide sequences of SEQ ID Nos. 1 , 3, 5 and 7 as well as those encoding the amino acid sequences depicted in SEQ ID Nos. 2, 4, 6 and 8 it is possible to isolate identical or similar nucleic acid molecules which encode water- soluble ligand-binding proteins from other species or organisms, in particular orthologous water-soluble ligand-binding protein encoding genes from mammals. The term "orthologous" as used herein means homologous sequences in different species that arose from a common ancestor gene during speciation. Orthologous genes may or may not be responsible for a similar function; see, e.g., the glossary of the "Trends Guide to Bioinformatics", Trends Supplement 1998, Elsevier Science.

In a further aspect, the present invention provides a recombinant polynucleotide comprising a vector incorporating the polynucleotide of the present invention. Many suitable vectors are known to those skilled in molecular biology, the choice of which would depend on the function desired and include plasmids, cosmids, viruses, bacte ophages and other vectors used conventionally in genetic engineering. Methods which are well known to those skilled in the art can be used to construct various plasmids and vectors; see, for example, the techniques described in Sambrook, Molecular Cloning A Laboratory Manual, Cold Spring Harbor Laboratory (1989) N.Y. and Ausubel, Current Protocols in Molecular Biology, Green Publishing Associates and Wiley Interscience, N.Y. (1989), (1994). Alternatively, the polynucleotides and vectors of the invention can be reconstituted into liposomes for delivery to target cells. As discussed in further details below, a cloning vector was used to isolate individual sequences of DNA. Relevant sequences can be transferred into expression vectors where expression of a particular polypeptide is required. Typical cloning vectors include pBscpt sk, pGEM, pUC9, pBR322 and pGBT9. Typical expression vectors include pTRE, pCAL-n-EK, pESP-1 , pOP13CAT, pET, pGEX, pMALC, pPIC9, pBac.

Hence, in a preferred embodiment of the present invention the above-described polyncucleotides either alone or present in a vector are linked to control sequences which allow the expression of the polynucleotide in prokaryotic and/or eukaryotic cells.

The term "control sequence" refers to regulatory DNA sequences which are necessary to effect the expression of coding sequences to which they are ligated. The nature of such control sequences differs depending upon the host organism. In prokaryotes, control sequences generally include promotor, ribosomal binding site, and terminators. In eukaryotes generally control sequences include promotors, terminators and, in some instances, enhancers, transactivators or transcription factors. The term "control sequence" is intended to include, at a minimum, all components the presence of which are necessary for expression, and may also include additional advantageous components.

The term "operably linked" refers to a juxtaposition wherein the components so described are in a relationship permitting them to function in their intended manner. A control 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. In case the control sequence is a promotor, it is obvious for a skilled person that double-stranded nucleic acid is preferably used. Thus, the vector of the invention is preferably an expression vector. An "expression vector" is a construct that can be used to transform a selected host cell and provides for expression of a coding sequence in the selected host. Expression vectors can for instance be cloning vectors, binary vectors or integrating vectors. Expression comprises transcription of the nucleic acid molecule preferably into a translatable mRNA. Regulatory elements ensuring expression in prokaryotic and/or eukaryotic cells are well known to those skilled in the art. In the case of eukaryotic cells they comprise normally promotors ensuring initiation of transcription and optionally poly-A signals ensuring termination of transcription and stabilization of the transcript. Possible regulatory elements permitting expression in prokaryotic host cells comprise, e.g., the PL, lac, trp, T7 or tac promotor in E. coli, and examples of regulatory elements permitting expression in eukaryotic host cells are the AOX1 or GAL1 promotor in yeast or the CMV-, SV40-, RSV-promotor (Rous sarcoma virus), CMV-enhancer, SV40-enhancer or a globin intron in mammalian and other animal cells. In this context, suitable expression vectors are known in the art such as Okayama-Berg cDNA expression vector pcDV1 (Pharmacia), pCDM8, pRc/CMV, pcDNAI , pcDNA3 (In-vitrogene), pSPORTI (GIBCO BRL). An alternative expression system which could be used to express the protein is an insect system. In one such system, Autographa californica nuclear polyhedrosis virus (AcNPV) is used as a vector to express foreign genes in Spodoptera frugiperda cells or in Trichoplusia larvae. The coding sequence of a nucleic acid molecule of the invention may be cloned into a nonessential region of the virus, such as the polyhedrin gene, and placed under control of the polyhedrin promotor. Successful insertion of said coding sequence will render the polyhedrin gene inactive and produce recombinant virus lacking coat protein coat. The recombinant viruses are then used to infect S. frugiperda cells or Trichoplusia larvae in which the protein of the invention is expressed (Smith, J. Virol. 46 (1983), 584; Engelhard, Proc. Nat. Acad. Sci. USA 91 (1994), 3224-3227).

In plants, promotors commonly used are the polyubiquitin promotor, and the actin promotor for ubiquitous expression. The termination signals usually employed are from the Nopaline Synthase promotor or from the CAMV 35S promotor. A plant translational enhancer often used is the TMV omega sequences, the inclusion of an intron (lntron-1 from the Shrunken gene of maize, for example) has been shown to increase expression levels by up to 100-fold. (Mait, Transgenic Research 6 (1997), 143-156; Ni, Plant Journal 7 (1995), 661-676). Additional regulatory elements may include transcriptional as well as translational enhancers. Advantageously, the above-described vectors of the invention comprises a selectable and/or scorable marker. Selectable marker genes useful for the selection of transformed cells and, e.g., plant tissue and plants are well known to those skilled in the art and comprise, for example, antimetabolite resistance as the basis of selection for dhfr, which confers resistance to methotrexate (Reiss, Plant Physiol. (Life Sci. Adv.) 13 (1994), 143-149); npt, which confers resistance to the aminoglycosides neomycin, kanamycin and paromycin (Herrera-Estrella, EMBO J. 2 (1983), 987-995) and hygro, which confers resistance to hygromycin (Marsh, Gene 32 (1984), 481-485).

Useful scorable markers are also known to those skilled in the art and are commercially available. Advantageously, said marker is a gene encoding luciferase (Giacomin, PI. Sci. 116 (1996), 59-72; Scikantha, J. Bact. 178 (1996), 121), green fluorescent protein (Gerdes, FEBS Lett. 389 (1996), 44-47) or β-glucuronidase

(Jefferson, EMBO J. 6 (1987), 3901 -3907). This embodiment is particularly useful for simple and rapid screening of cells, tissues and organisms containing a vector of the invention. The proteins can be recovered and purified from recombinant cell cultures by well- known methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, size exclusion chromatography, affinity chromatography, hydroxylapatite chromatography and lectin chromatography. Most preferably, high performance liquid chromatography ("HPLC") or FPLC is employed for purification.

The present invention furthermore relates to host cells produced by introducing a nucleic acid molecule into the host cell which upon its presence in the cell mediates the expression of a gene encoding water-soluble ligand-binding proteins or comprising a polynucleotide or a vector as described above or a polynucleotide according to the invention wherein the polynucleotides and/or nucleic acid molecule is foreign to the host cell. By "foreign" it is meant that the polynucleotide or nucleic acid molecule is either heterologous with respect to the host cell, this means derived from a cell or organism with a different genomic background, or is homologous with respect to the host cell but located In a different genomic environment than the naturally occurring counterpart of said nucleic acid molecule. This means that, if the nucleic acid molecule is homologous with respect to the host cell, it is not located in its natural location in the genome of said host cell, in particular it is surrounded by different genes. In this case the polynucleotide may be either under the control of its own promotor or under the control of a heterologous promotor. The vector or nucleic acid molecule according to the invention which is present in the host cell may either be integrated into the genome of the host cell or it may be maintained in some form extrachromosomally. In this respect, it is also to be understood that the nucleic acid molecule of the invention can be used to restore or create a mutant gene via homologous recombination. The host cell can be any prokaryotic or eukaryotic cell, such as bacterial, insect, fungal, plant or animal cells.

The term "prokaryotic" is meant to include all bacteria which can be transformed or transfected with a DNA or RNA molecules for the expression of a protein of the invention. Prokaryotic hosts may include gram negative as well as gram positive bacteria such as, for example, E. coli, S. typhimurium, Serratia marcescens and Bacillus subtilis. The term "eukaryotic" is meant to include yeast, higher plant, insect and preferably mammalian cells. Depending upon the host employed in a recombinant production procedure, the protein encoded by the polynucleotide of the present invention may be glycosylated or may be non-glycosylated. The water- soluble ligand-binding protein of the invention may or may not also include an initial methionine amino acid residue. A polynucleotide of the invention can be used to transform or transfect the host using any of the techniques commonly known to those of ordinary skill in the art. Furthermore, methods for preparing fused, operably linked genes and expressing them in, e.g., mammalian cells and bacteria are well-known in the art (Sambrook, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1989).

Thus the present invention provides a cell capable of expressing a polypeptide as discussed herein. The cell comprises a recombinant host cell usually incorporating the polynucleotide. Preferably, the host cell incorporates the polynucleotide as the recombinant polynucleotide. Any suitable host cell may be chosen, again depending on the intended purpose. Suitable host cells include XLI-BLUE, B21(DE3)pLysS, HB101 , SOLR and SP-Q01 (Saccharomyces pombe). Using an appropriate combination of host cell, vector and polynucleotide, an expression system can be provided so as to obtain a polypeptide useful in the present invention. This may comprise a fusion polypeptide encoded by the recombinant polynucleotide, a part of which is encoded by the vector. Typically, the vector will have a promotor region, which is usually inducible, leading to 5' coding region associated with the promotor. By appropriate manipulation, the polynucleotide encoding the polypeptide can be attached to the 5' coding region in frame. In this way, expression of the nucleotide sequence downstream of the promotor region gives rise to the fusion polypeptide which includes the polypeptide of the present invention.

The present invention also relates to an antigen comprising an epitope of at least 5 continuous amino acids of the amino acid sequence depicted in any one of SEQ ID Nos. 2, 4, 6 or 8 and/or said epitope is detectable by a monoclonal or polyclonal antibody which recognises, preferably with a binding affinity of at least 10^'7M, a protein of the invention as described above. In the present invention, "epitopes" refers to fragments of the AChBP of the invention having antigenic or immunogenic activity in an animal. A preferred embodiment of the present invention relates to antigens comprising an epitope, as well as the polynucleotide encoding this fragment. A region of a protein molecule to which an antibody can bind is defined as an "antigenic epitope." In contrast, an "immunogenic epitope" is defined as a part of a protein that elicits an antibody response; see, for instance, Geysen, Proc. Natl. Acad. Sci. USA 81 (1983); 3998-4002. Fragments which function as epitopes may be produced by any conventional means; see, e.g., Houghten, Proc. Natl. Acad. Sci. USA 82 (1985), 5131-5135 further described in U.S. Patent No. 4,631 ,211. In the present invention, antigenic epitopes preferably contain a sequence of at least five, six, seven, more preferably at least nine, and most preferably between about 15 to about 30 amino acids. Antigenic epitopes are useful to raise antibodies, including monoclonal antibodies, that specifically bind the epitope; see, for instance, Wilson, Cell 37 (1984), 767-778; Sutcliffe, Science 219 (1983), 660-666). Similarly, immunogenic epitopes can be used to induce antibodies according to methods well known in the art; see, for instance, Sutcliffe, supra; Wilson, supra; Chow, Proc. Natl. Acad. Sci. USA 82 (1985), 910-914; and Bittle, J. Gen. Virol. 66 (1985); 2347-2354. A preferred immunogenic epitope includes the soluble protein. The immunogenic epitopes may be presented together with a carrier protein, such as an albumin, to an animal system (such as rabbit or mouse) or, if it is long enough (at least about 25 amino acids), without a carrier. However, immunogenic epitopes comprising as few as 8 to 10 amino acids have been shown to be sufficient to raise antibodies capable of binding to, at the very least, linear epitopes in a denatured polypeptide (e.g., in Western blotting.)

The present invention also relates to antibodies specifically recognizing the water- soluble ligand-binding protein and ligand-gated ion channels of the present invention, in particular recognizing the above described antigen or epitope. As used herein, the term "antibody" (Ab) or "monoclonal antibody" (Mab) is meant to include intact molecules as well as antibody fragments (such as, for example, Fab and F(ab')₂ fragments) which are capable of specifically binding to protein. Fab and F(ab')₂ fragments lack the Fc fragment of intact antibody, clear more rapidly from the circulation, and may have less non-specific tissue binding than an intact antibody; see, e.g., Wahl, J. Nucl. Med. 24 (1983), 316-325. Thus, these fragments are preferred, as well as the products of a FAB or other immunoglobulin expression library. Moreover, antibodies of the present invention include chimeric, single chain, and humanized antibodies; see also infra. Said antibody can be a monoclonal antibody, a polyclonal antibody, a single chain antibody, human or humanized antibody, primatized, chimerized or fragment thereof that specifically binds said peptide or polypeptide also including bispecific antibody, synthetic antibody, antibody fragment, such as Fab, Fv or scFv fragments etc., or a chemically modified derivative of any of these. The general methodology for producing antibodies is well-known and has been described in, for example, Kohler and Milstein, Nature 256 (1975), 494 and reviewed in J.G.R. Hurrel, ed., "Monoclonal Hybridoma Antibodies: Techniques and Applications", CRC Press Inc., Boco Raron, FL (1982), as well as that taught by L. T. Mimms et al., Virology 176 (1990), 604-619. Furthermore, antibodies or fragments thereof to the aforementioned peptides can be obtained by using methods which are described, e.g., in Harlow and Lane "Antibodies, A Laboratory Manual", CSH Press, Cold Spring Harbor, 1988. For the production of antibodies in experimental animals, various hosts including goats, rabbits, rats, mice, and others, may be immunized by injection with polypeptides of the present invention or any fragment or oligopeptide or derivative thereof which has immunogenic properties. Techniques for producing and processing polyclonal antibodies are known in the art and are described in, among others, Mayer and Walker, eds., "Immunochemical Methods in Cell and Molecular Biology", Academic Press, London (1987). Polyclonal antibodies also may be obtained from an animal, preferably a mammal, previously infected with the virus of the invention. Methods for purifying antibodies are known in the art and comprise, for example, immunoaffinity chromatography. Depending on the host species, various adjuvants or immunological carriers may be used to increase immunological responses. Such adjuvants include, but are not limited to, Freund's, complete or incomplete adjuvants, mineral gels such as aluminium hydroxide, and surface active substances such as lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions and dinitrophenol. An example of a carrier, to which, for instance, a peptide of the invention may be coupled, is keyhole limpet hemocyanin (KLH). When derivatives of said antibodies are obtained by the phage display technique, surface plasmon resonance as employed in the BIAcore system can be used to increase the efficiency of phage antibodies which bind to an epitope of the peptide or polypeptide of the invention (Schier, Human Antibodies Hybridomas 7 (1996), 97-105; Malmborg, J. Immunol. Methods 183 (1995), 7-13). In many cases, the binding phenomena of antibodies to antigens is equivalent to other ligand/anti-ligand binding. In another embodiment the present invention relates to an oligonucleotide probe comprising a nucleotide sequence having at least 15 continuous nucleotides of a polynucleotide of the invention and/or encoding the above described antigen. Such oligonucleotides will usually specifically hybridize to a polynucleotide encoding a water-soluble ligand-binding protein of the invention. Specific hybridization occurs preferably under stringent conditions and implies no or very little cross-hybridization with nucleotide sequences encoding no or substantially different proteins. Such nucleic acid molecules may be used as probes and/or for the control of gene expression. Nucleic acid probe technology is well known to those skilled in the art who will readily appreciate that such probes may vary in length. Preferred are nucleic acid probes of 17 to 35 nucleotides in length. Of course, it may also be appropriate to use nucleic acids of up to 100 and more nucleotides in length. The nucleic acid probes of the invention are useful for various applications. On the one hand, they may be used as PCR primers for amplification of polynucleotides according to the invention. Another application is the use as a hybridization probe to identify polynucleotides hybridizing to the polynucleotides of the invention by homology screening of genomic DNA libraries. Nucleic acid molecules according to this preferred embodiment of the invention which are complementary to a polynucleotide as described above may also be used for repression of expression of a gene comprising such a polynucleotide, for example due to an antisense or triple helix effect or for the construction of appropriate ribozymes (see, e.g., EP-B1 0 291 533, EP-A1 0 321 201 , EP-A2 0 360 257) which specifically cleave the (pre)-mRNA of a gene comprising a polynucleotide of the invention. Selection of appropriate target sites and corresponding ribozymes can be done as described for example in Steinecke, Ribozymes, Methods in Cell Biology 50, Galbraith et al. eds Academic Press, Inc. (1995), 449-460. Standard methods relating to antisense technology have also been described (Melani, Cancer Res. 51 (1991), 2897-2901). Said nucleic acid molecules may be chemically synthesized or transcribed by an appropriate vector containing a chimeric gene which allows for the transcription of said nucleic acid molecule in the cell. Such nucleic acid molecules may further contain ribozyme sequences as described above.

In this respect, it is also to be understood that the polynucleotide of the invention can be used for "gene targeting" and/or "gene replacement", for restoring a mutant gene or for creating a mutant gene via homologous recombination; see for example Mouellic, Proc. Natl. Acad. Sci. USA, 87 (1990), 4712-4716; Joyner, Gene Targeting, A Practical Approach, Oxford University Press. Furthermore, the person skilled in the art is well aware that it is also possible to label such a nucleic acid probe with an appropriate marker for specific applications, such as for the detection of the presence of a polynucleotide of the invention in a sample derived from an organism, in particular mammals, preferably human. A number of companies such as Pharmacia Biotech (Piscataway NJ), Promega (Madison Wl), and US Biochemical Corp (Cleveland OH) supply commercial kits and protocols for these procedures. Suitable reporter molecules or labels include those radionuclides, enzymes, fluorescent, chemiluminescent, or chromogenic agents as well as substrates, cofactors, inhibitors, magnetic particles and the like. Patents teaching the use of such labels include US Patents US-A-3,817,837; US-A-3,850,752; US-A- 3,939,350; US-A-3,996,345; US-A-4,227,437; US-A-4,275,149 and US-A-4,366,241. Also, recombinant immunoglobulins may be produced as shown in US-A-4,816,567 incorporated herein by reference. Furthermore, the so-called "peptide nucleic acid" (PNA) technique can be used for the detection or inhibition of the expression of a polynucleotide of the invention. For example, the binding of PNAs to complementary as well as various single stranded RNA and DNA nucleic acid molecules can be systematically investigated using thermal denaturation and BIAcore surface-interaction techniques (Jensen, Biochemistry 36 (1997), 5072-5077).

The present invention also relates to a method for the production of a transgenic non- human animal, preferably transgenic mouse, comprising introduction of a polynucleotide or vector of the invention into a germ cell, an embryonic cell, stem cell or an egg or a cell derived therefrom. The non-human animal can be used in accordance with a screening method of the invention described herein. Production of transgenic embryos and screening of those can be performed, e.g., as described by A. L. Joyner Ed., Gene Targeting, A Practical Approach (1993), Oxford. University Press. The DNA of the embryonal membranes of embryos can be analyzed using, e.g., Southern blots with an appropriate probe; see supra. The invention also relates to transgenic non-human animals such as transgenic mouse, rats, hamsters, dogs, monkeys, rabbits, pigs, C. elegans and fish such as Torpedo fish comprising a polynucleotide or vector of the invention or obtained by the method described above, preferably wherein said polynucleotide or vector is stably integrated into the genome of said non-human animal, preferably such that the presence of said polynucleotide or vector leads to the expression of the water-soluble protein of the present invention. The present invention further relates to composition comprising any one of the above described water-soluble ligand-binding proteins, multimers such as dimers or pentamers thereof, ligand-gated ion channels, polynucleotides, vectors, host cells, antigens, antibodies, or oligonucleotide probes of the invention; and optionally suitable means for detection or performing a ligand-receptor binding assay. In this context, the present invention also relates to a method for identifying an agonist/activator or antagonist/inhibitor of a ligand-gated receptor comprising the steps of:

(a) contacting the water-soluble ligand-binding protein of the present invention, multimers such as dimers or pentamers thereof, or the ligand-gated ion channel of the invention or a cell expressing said protein in the presence of components capable of providing a detectable signal in response to ligand binding with a compound to be screened under conditions that permit binding of said compound to the ligand-binding protein; and (b) detecting the presence or absence of a signal generated from the binding activity of the ligand-binding protein, wherein the presence/increase and absence/decrease of the signal is indicative for an agonist/activator and antagonist/inhibitor, respectively, of a ligand-gated receptor.

Since ligand-gated receptors are modulated allosterically by natural polyamines, such as spermine, and by polyamine derivatives, such as polyamine amides (e.g. philanthotoxin-343) and polymethylene tetraamines (e.g. methoctramine) (Usherwood, Farmaco. 55 (2000), 202-205) compounds comprising or based on such entities may be used as starting material for screening. An antagonist or agonist that "modulates the activity" of a polypeptide and causes an altered signal, for example response in the cell refers to a compound that alters the activity of the protein so that it behaves differently in the presence of the compound than in the absence of the compound. Typically, the effect of an antagonist is observed as a blocking of agonist-induced receptor activation. Antagonists include competitive as well as non-competitive antagonists. A competitive antagonist (or competitive blocker) interacts with or near the site specific for agonist binding. A non-competitive antagonist or blocker inactivates the function of the receptor by interacting with a site other than the agonist interaction site. As understood by those of skill in the art, bioassay methods for identifying compounds that modulate the activity of receptors such as proteins of the invention generally require comparison to a control. One type of "control" is a cell or culture that is treated substantially the same as the test cell or test culture exposed to the compound, with the distinction that the "control" cell or culture is not exposed to the compound. For example, in methods that use voltage clamp electrophysiological procedures, the same cell can be tested in the presence or absence of compound, by merely changing the external solution bathing the cell.

Accordingly, the response of the transfected cell to the "control" cell or culture to the same compound under the same reaction conditions. However, "control data" can also be used from the literature.

As described in Example 6 the 3-dimensional structure of AChBP could be solved by X-ray crystallography at 2.7A resolution (current Rfactor = 27.9 %, Rfree = 30.0 %). In crystals, as in solution, AChBP forms a stable homo-pentamer with dimensions comparable to those of the ligand-binding domain of ligand-gated ion channels, in particular comparable to the nAChR, as determined in EM studies by Unwin and coworkers; see supra. The structural analysis revealed that in the AChBP homopentamer the monomers have immunoglobulin-like topology. At each of five subunit interfaces a ligand-binding site is located, with all residues consistent with biochemical data. In this site a buffer molecule (HERPES) stacks with cation-π interactions on a tryptophan, resembling acetylcholine binding. The AChBP structure is relevant for the development of drugs against, e.g., Alzheimer's disease and nicotine addiction. The high-resolution crystal structure of AChBP, along with biochemical and pharmacological data, supports the teaching of the present invention that the water-soluble ligand-binding proteins of the invention such as AChBP are good mimics of ligand-binding domains of ligand-gated ion channels.

Thus, the present invention relates to a crystal of a water-soluble ligand-binding protein of the invention, preferably in a multimeric form such as dimer, pentamer or decamer. In one embodiment said crystal comprises a protein-ligand complex.

Methods how to employ and analyze such crystals are known to the person skilled in the art; see for example US-A-5, 872,011 which describes the crystal structure of a protein-ligand complex containing an N-terminal truncated elF4E and uses thereof. The crystal structure of the ligand-gated receptor ligand-binding region in a complex with a ligand, preferably being an antagonist or agonist will reveal the determinants of receptor-antagonist/agonist interactions and how ligand-binding specificity and affinity are altered by remote residues and the redox state of the conserved disulphide bond. The structure may also indicate mechanisms for allosteric effector action and for ligand-induced channel gating. How the information on the crystal structure of a ligand-binding region in a complex with a ligand can be used for the development of agonists and antagonists has been described for the structure of a g I utamate- receptor ligand-binding core in complex with kainate (Armstrong et al.,

Nature 395 (1998), 913-917).

The crystal of the invention, in particular when comprising nAChR related proteins can be a complex of the protein with a ligand comprising an N-alkylated hydroxyalkyl and/or a quaternary ammonium ion. However, other ligands my be used as well. Preferred ligands comprise 4-(2-Hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), B-bippinatin, lophotoxin, d-tubocurarine, nicotine, acetylcholine, conotoxin, carbamylcholine, galanthamine, epibatidine or alpha-bungarotoxin or derivatives thereof.

Different aspects of X-ray crystallography are such as data collection, structure solution, determining the molecular structure from X-ray diffraction, refinement, etc. are described in the prior art, see, e.g., Powell, Annu. Rep. Prog. Chem., Sect. C: Phys. Chem. 96 (2000), 139-175 and Methods in Enzymology, 276-277, edited by Carter and Sweet, Academic Press, 1997. Current methods and optimization algorithms for the refinement of X-ray crystal structures are described by Van Der Maelen Uria, Crystallogr. Rev. 7 (1999), 125-180. The crystal of the invention effectively diffracts X-rays for the determination of the atomic coordinates of the protein or protein-ligand complex to a resolution of greater than 5.0, preferably greater than 4.0 Angstroms. In a preferred embodiment the crystal effectively diffracts X-rays for the determination of the atomic coordinates of the protein-ligand complex to a resolution of greater than 3.0 Angstroms. In a more preferred embodiment the crystal effectively diffracts X-rays for the determination of the atomic coordinates of the protein-ligand complex to a resolution of greater than 2.0 Angstroms. In one embodiment the crystal effectively diffracts X-rays for the determination of the atomic coordinates of the protein-ligand complex to a resolution of about 2.7 Angstroms.

Preferably, the crystal of the invention is formed by a protein that has an amino acid sequence of amino acids 20 to 223 of SEQ ID No. 2, or an amino acid sequence that differs from amino acid 20 to 223 of SEQ ID No. 2 by only having conservative substitutions. As is described in the examples, the crystals of the AChBP comprise decameric forms of the protein. In order to ease the use of the AChBP protein for analysis and crystallography it is envisaged to create a mutation in residue Asp2 and Asp5 of the mature AChBP SEQ ID No. 2 or 4 to remove the calcium binding site, and prevent creation of a decamer. This deletion can be done for example by oligonucleotide-directed mutagenesis. Alternatively crystals could be grown in a low calcium concentration or in the absence of calcium.

The crystal of the present invention preferably has (1 ) a space group of P2ι2^ and a unit cell of dimensions of a=120.6A, b=137.θA and c=161.5A; (2) a space group of P4₂2-i2 and a unit cell of dimensions of a=b=141.6A and c=120.8A or (3) a space group of Pλ_Λ and a unit cell of dimensions of a=121.lA, b=162.lA, c=139.4A, ^β=90.1 °. The crystal of the present invention is preferably from a protein that has secondary structural elements that include .alpha.-helix and antiparallel .beta.-sheets as shown in and described for Figures 7, 10, 1 1 and/or 12. Most preferably, the crystal of the invention has a three-dimensional structure as defined by atomic coordinates shown in Table 1. Those of skill in the art understand that a set of structure coordinates determined by X-ray crystallography is not without standard error. For the purpose of this invention, any set of structure coordinates for AChBP or AChBP mutants that have a root mean square deviation of protein backbone atoms (N, C.alpha., C and O) of less than 0.75 Angstrom when superimposed - using backbone atoms - on the structure coordinates listed in Table 1 shall be considered identical. In a most preferred embodiment of the present invention, the crystal has a binding cavity as shown in Figures 6, 8, 9 and/or 13.

In accordance with the findings of the present invention, it is proposed to use the water-soluble ligand-binding proteins of molluscs as the blueprint for the receptor binding site of the ligand-gated ion channel superfamily including nACh, 5-HT3, glycine, GABA_A, and GABA_Cl most preferably for the nAChR. The availability of X-ray structures, and the cloned sequences provide a unique opportunity to understand these receptors at the molecular level, possibly unravel the dynamic changes occurring upon ligand binding, and predict their tertiary and quaternary structure with a higher degree of confidence than possible for other protein modules. This should pave the way for designing ligands selective for any of the multiple subtypes in any of these receptor families. The AChBP-like structures can be used for computerized docking to homology models which leads to the a priori discovery of novel ligands before laboratory experiments begin to optimize the drug candidates. Thus, the present invention also relates to a method of using the crystal of the invention in a drug screening assays, such as comprising: (a) selecting a potential ligand by performing structure assisted drug design with the three-dimensional structure determined for the crystal, wherein said selecting is performed in conjunction with computer modeling; optionally

(b) contacting the potential ligand with the ligand binding domain of the ligand-gated receptor in an in vitro or in vivo assay; and (c) detecting the binding of the potential ligand for the ligand binding domain.

The use of macromolecular crystallography as a tool for investigating drug and receptor interactions, in particular structure-based drug design is reviewed in Oakley and Wilce, Clin. Exp. Pharmacol. Physiol. 27 (2000), 145-151. The desired drug could be an inhibitor or an agonist that mimics endogenous transmitters or ligands. Once the 3-D structure of the relevant target is known, computational processes can be used to search databases of compounds to identify ones that may interact strongly with the target. Lead compounds can be improved using the 3-D structure of the complex of the lead compound and its biological target. The activity of the selected compound can then be tested in a functional assay such as one of those described herein.

Preferably, the potential drug is selected on the basis of its having a greater affinity for the ligand binding domain of the ligand-gated receptor than that of a standard ligand for the ligand binding domain of the ligand-gated receptor. However, the affinity of the selected compound may also be less than that of a standard ligand. Such compounds are useful for example as a lead for the development of further analogues which in turn may have enhanced binding affinity or otherwise beneficial therapeutic properties. On the other hand, the selected compound may bind to a site of the ligand-gated receptor other than known ligands. In a preferred embodiment, the ligand-gated receptor is a nicotinic acetylcholine receptor.

In a further embodiment, the method of the present invention further comprises: (d) forming a supplemental crystal of a protein-ligand complex by co- crystallization or soaking the crystal of the water-soluble ligand-binding protein with a potential drug, wherein the crystal effectively diffracts X-rays for the determination of the atomic coordinates of the protein-ligand complex to a resolution of greater than 5.0, preferably greater than 4.0 Angstroms, more preferably greater than 3; (e) determining the three-dimensional structure of the supplemental crystal; (f) selecting a candidate drug by performing a structure assisted drug design with the three-dimensional structure determined for the supplemental crystal, wherein said selecting is performed in conjunction with computer modeling; optionally (g) contacting the candidate drug with a cell that expresses the ligand- gated receptor; and (h) detecting a cell response; wherein a candidate drug is identified as a drug when the cell response is altered compared to a cell that has not been contacted with the candidate compound. The above described methods can further comprise an initial step that precedes step (a) wherein said initial step consists of determining the three-dimensional structure of a crystal comprising a protein-ligand complex formed between the water-soluble ligand-binding protein, and the ligand of the ligand-gated receptor, wherein the crystal effectively diffracts X-rays for the determination of the atomic coordinates of the protein-ligand complex to a resolution of greater than 5.0, preferably greater than 4.0 Angstroms. Preferably, the resolution of crystal diffraction in the above described methods is at least 3.0, most preferably at least about 2.7 Angstroms.

In a still further embodiment, the present invention relates to a method of growing a crystal of a protein-ligand complex comprising:

(a) contacting the water-soluble ligand-binding protein described above with a ligand of a ligand-gated receptor, wherein the water-soluble ligand-binding protein forms a protein-ligand complex with the ligand; and

(b) growing the crystal of the protein-ligand complex; wherein the crystal effectively diffracts X-rays for the determination of the atomic coordinates of the protein-ligand complex to a resolution of greater than 5.0, preferably greater than 4.0 Angstroms, more preferably at least 3.0, most preferably at least about 2.7 Angstroms.

The crystals of the present invention can also be used in X-ray crystallography- driven screening technique that combines the steps of lead identification, structural assessment, and optimization such as described for example in Nienaber et al., Nature Biotechnol. 18 (2000), 1105 - 1108. This crystallographic screening method (named CrystaLEAD) has been used to sample . large compound libraries and detecting ligands by monitoring changes in the electron density map of the crystal relative to the unbound form. The electron density map yields a high- resolution picture of the ligand-protein complex that provides key information to a structure- directed drug discovery process. The bound ligand is directly visualized in the electron density map. Ligands that bind away from the targeted site may be eliminated.

The above described methods can be coupled with state-of-the-art laboratory data collection facilities including CCD detectors and data acquisition robotics.

Further embodiments that may be used in accordance with the ligand-binding proteins and receptor of the present invention are described in the prior art, for example ligand screening and design by X-ray crystallography is disclosed in W099/45379 and W099/45389; WOOO/14105 describes assaying a candidate compound for its ability to interact with a modified receptor tyrosine kinase including obtaining and applying crystallography coordinates to a computer algorithm for generating a model which is applied in an iterative process to various molecular structures in order to identify agonist and antagonists of the receptor. All these methods may be equally applied to the proteins and crystals of the present invention.

In one preferred embodiment, the present invention relates to a drug screening assay comprising soaking a crystal of the invention in a solution of compounds to be screened and detecting the binding of the compound to the ligand-binding protein. A possible procedure is also described in Example 9. Besides the detection methods of ligand-binding mentioned above, in the cited documents and in the examples, the detection can also be based on measuring the release of the ligand in the preformed crystal of a protein-ligand complex. As described herein before, said ligand preferably comprises an alkylated nitrogen and/or quaternary ammonium ion or may be one of those described above.

The structural information on the crystals of the present invention can also be used for increasing or decreasing the affinity of a drug to a ligand-gated receptor. Such a method can comprise performing structure assisted drug design with the three- dimensional structure determined for the crystal, wherein said drug design is performed in conjunction with computer modeling; and modifying said drug to alter or eliminate a portion thereof suspected of interacting with a binding site of the binding cavity or with a non-specific binding site of the protein in the crystal. This method can, of course, be combined with one or. more steps of any of the above described screening methods or other screening methods well known in the art. Methods for clinical compound discovery comprises for example ultrahigh-throughput screening (Sundberg, Curr. Opin. Biotechnol. 1 1 (2000), 47-53) for lead identification, and structure-based drug design (Verlinde and Hoi, Structure 2 (1994), 577-587) and combinatorial chemistry (Salemme et al., Structure 15 (1997), 319-324) for lead optimization. Further information that could be taken into account for drug selection and design so far available for the localization of agonist and competitive antagonist binding sites on nicotinic acetylcholine receptors have recently been reviewed (Arias,

Neurochem. Int. 36 (2000), 595-6450; Corringer et al., 1999). Once a drug has been selected, the method can have the additional step of repeating the method used to perform rational drug design using the modified drug and to assess whether said modified drug displays better affinity according to for example interaction/energy analysis.

A related method of the present invention for drug design comprises the step of using the structural coordinates of the water-soluble ligand-binding protein crystal comprising the coordinates of Table 1 , to computationally evaluate a chemical entity for associating with the ligand-binding site or a non-specific binding site of a ligand- binding protein. This approach, made possible and enabled by this invention, is to screen computationally small molecule data bases for chemical entities or compounds that can bind in whole, or in part, to the AChBP. In this screening, the quality of fit of such entities or compounds to the binding site may be judged either by shape complementarity or by estimated interaction energy. Meng, et al., J. Coma. Chem. 13 (1992), 505-524. In addition, in accordance with this invention, AChBP mutants or chimerics may be crystallized in co-complex with known ligand-gated ion channel inhibitors. The crystal structures of a series of such complexes may then be solved by molecular replacement (for review see for example Brunger er al. Prog. Biophys. Mol. Biol. 72 (1999), 135-155; and references cited therein) and compared with that of wild-type AChBP. Potential sites for modification within the various binding sites of the ligand-binding domain may thus be identified. This information provides an additional tool for determining the most efficient binding interactions, for example, increased hydrophobic interactions, between AChPB and a chemical entity or compound. The design of compounds that bind to or inhibit ligand-gated ion channels according to this invention generally involves consideration of two factors. First, the compound must be capable of physically and structurally associating with the ligand-binding domain. Non-covalent molecular interactions important in the association of the ligand-binding domain with its ligand include hydrogen bonding, van der Waals and hydrophobic interactions.

Second, the compound must be able to assume a conformation that allows it to associate with the ligand-binding domain. Although certain portions of the compound will not directly participate in this association, those portions may still influence the overall conformation of the molecule. This, in turn, may have a significant impact on potency. Such conformational requirements include the overall three-dimensional structure and orientation of the chemical entity or compound in relation to all or a portion of the binding site or the spacing between functional groups of a compound comprising several chemical entities that directly interact with the AChBP.

If the theoretical structure of the given compound suggests insufficient interaction and association between it and AChBP, synthesis and testing of the compound is obviated. However, if computer modelling indicates a strong interaction, the molecule may then be synthesized and tested for its ability to bind to AChPB or a ligand-gated ion channel and functionally tested according to the methods mentioned above. In this manner, synthesis of inoperative compounds may be avoided. Once suitable chemical entities or fragments have been selected, they can be assembled into a single compound or inhibitor. Assembly , may be proceed by visual inspection of the relationship of the fragments to each other on the three-dimensional image displayed on a computer screen in relation to the structure coordinates of AChBP. This would be followed by manual model building using software such as Quanta or Sybyl. Useful programs to aid one of skill in the art in connecting the individual chemical entities or fragments include CAVEAT (Bartlett, et al, "CAVEAT: A Program to Facilitate the Structure-Derived Design of Biologically Active Molecules". In Molecular Recognition in Chemical and Biological Problems", Special Pub., Royal Chem. Soc. 78 (1989), 182-196); 3D Database systems such as MACCS-3D (Martin, J. Med. Chem. 35 (1992), 2145-2154) and HOOK (Molecular Simulations, Burlington, Mass.). Instead of proceeding to build an AChBP ligand in a step-wise fashion one fragment or chemical entity at a time as described above, AChBP binding compounds may be designed as a whole or "de novo" using either an empty active site or optionally including some portion(s) of a known ligand(s). These methods include LUDl (Bohm, J. ComR. Aid. Molec. Design 6 (1992), 61-78); LEGEND (Nishibata and Itai, Tetrahedron 47 (1991), 8985); and LeapFrog (Tripos Associates, St. Louis, Mo.). Other molecular modelling techniques may also be employed in accordance with this invention; see, e.g., Cohen, J. Med. Chem. 33 (1990), 883-894 and Navia and Murcko, Current Opinions in Structural Biology 2 (1992), 202-210. Such computer modeling is preferably performed with a Docking program (Dunbrack et al., Protein Sci. 6 (1997), 1661 -1681 and Folding Des. 2 (1997), R27-R42).

Methods for the identification of drugs or corresponding lead compounds in computational prescreen using X-ray crystal structures are described in the prior art (Veriinde and Hoi, Structure 2 (1994), 577-587; Kuntz, Science 257 (1992), 1078-

1082; Shuker et al., Science 274 (1996), 1531-1534; Fejzo et al., Chem. Biol. 6

(1999), 755-769; WO 98/58961). The structural information can be consulted to efficiently optimize leads. Computational programs have been written to identify compounds ranging from very small molecules or functional groups (GRID:

Goodford, J. Med. Chem. 28 (1985), 849-857; MCSS: Caflish et al., J. Med. Chem.

36 (1993), 2142-2167) to potential lead scaffolds (DOCK: Kuntz et al., Accounts

Chem. Res. 27 (1994), 1 17-123) using solved X-ray crystal structures. Another method computationally prescreens compound libraries and experimentally tests the individual "hits" by X-ray crystallography (Veriinde et al., J. Comput. Aided Mol. Des. 6 (1992), 131-147) in order to decrease the size of the screening library. In addition, an experimental approach has been developed to find organic solvents that bind to active sites that may be recombined into a lead macromolecule (Allen et al., J. Phys. Chem. 100 (1996), 2605-2611).

Once a compound has been designed or selected by the above methods, the efficiency with which that compound may bind to the AChBP or a corresponding ligand-binding domain may be tested and optimized by computational evaluation. For example, a compound that has been designed or selected to function as an inhibitor must preferably demonstrate a relatively small difference in energy between its bound and free states (i.e., a small deformation energy of binding). Thus, the most efficient inhibitors should preferably be designed with a deformation energy of binding of not greater than about 10 kcal/mole, preferably, not greater than 7 kcal/mole. Inhibitors may interact with the ligand-binding domain in more than one conformation that is similar in overall binding energy. In those cases, the deformation energy of binding is taken to be the difference between the energy of the free compound and the average energy of the conformations observed when the inhibitor binds to the AChBP.

A compound designed or selected as binding to AChBP may be further computationally optimized so that in its bound state it would preferably lack repulsive electrostatic interaction with the target ligand-binding domain. Such non- complementary (e.g., electrostatic) interactions include repulsive charge-charge, dipole-dipole and charge-dipole interactions. Specifically, the sum of all electrostatic interactions between the ligand and the AChBP when the ligand is bound to AChBP, preferably make a neutral or favorable contribution to the enthalpy of binding. Specific computer software is available in the art to evaluate compound deformation energy and electrostatic interaction. Examples of programs designed for such uses include Gaussian 92, revision C (Frisch, Gaussian, Inc., Pittsburgh, Pa.); AMBER, version 4.0 (Kollman, University of California at San Francisco); QUANTA/CHARMM (Molecular Simulations, Inc., Burlington, Mass.); and Insight ll/Discover (Biosysm Technologies Inc., San Diego, Calif.). These programs may be implemented, for instance, using a Silicon Graphics workstation, IRIS 4D/35, IBM RISC/6000 workstation model 550 or better a Unix workstation (SGI, Alpha, Sun, etc.) or any Linux PC. Other hardware systems and software packages will be known to those skilled in the art. Once an AChBP-binding compound has been optimally selected or designed, as described above, substitutions may then be made in some of its atoms or side groups in order to improve or modify its binding properties. Generally, initial substitutions are conservative, i.e., the replacement group will have approximately the same size, shape, hydrophobicity and charge as the original group. It should, of course, be understood that components known in the art to alter conformation should be avoided. Such substituted chemical compounds may then be analyzed for efficiency of fit to AChBP by the same computer methods described in detail, above. As mentioned before, the above described methods of the present invention can also be used as an initial drug screening assay followed by a classical drug screening assay using the biochemical assays known in the art.

Methods for the preparation of compounds, chemical derivatives and analogues are well known to those skilled in the art and are described in, for example, Beilstein, Handbook of Organic Chemistry, Springer edition New York Inc., 75 Fifth Avenue, New York, N.Y.

In one embodiment of the method of the present invention the identified drug prevents or promotes correct assembly of a ligand-gated ion channel. Thus, the selected drug may for example either interfere with the contact regions of the monomers of the ligand-gated ion channel or may act as a scaffold for the assembly. In the latter case, the drug may be based for example on an antibody which binds to the contact regions of two or more monomers when assembled and thus facilitates the assembly process. Preferred contact regions with respect to the AChBP and the related nicotinic acetylcholine receptor are given below. In a still further embodiment of the above described methods, the drug can be selected such as to bind to a non- specific binding site of a ligand-gated ion channel. The non-specific binding site can for example include those contact regions that are highly conserved between the monomers of the ligand-gated ion channels. Once a drug has been selected in accordance with any one of the above described methods of the present invention, the drug or a pro-drug thereof can be synthesized in a therapeutically effective amount. As used herein, the term "therapeutically effective amount" means the total amount of the drug or pro-drug that is sufficient to show a meaningful patient benefit, i.e., treatment, healing, prevention or amelioration of a condition related to an ligand-gated ion channel, or an increase in rate of treatment, healing, prevention or amelioration of such conditions. In addition or alternatively, in particular with respect to pre-clinical testing of the drug the term "therapeutically effective amount" includes the total amount of the drug or pro-drug that is sufficient to elicit a physiological response upon its binding to its target ligand- gated ion channel in an non-human animal test.

The present invention also relates to a drug produced by any one of the above described methods of the present invention, or a pro-drug thereof. Preferably, the drug or pro-drug thereof is present either alone or in a composition in a therapeutically effective amount.

The drug obtained by a method of the present invention may be characterized by its interaction with the binding sites in the binding cavity defined by the coordinates of crystal structure of the protein-ligand complex; for examples of such characterization see, e.g., US-A-5, 798,247. Preferably, the drug, for example a potential inhibitor will form non-covalent bonds with one or more amino acids in the active site based upon the crystal structure. On the other hand, the drug may bind to a contact region of the individual monomers of the pentameric ligand-gated receptor. For example, multimer contact regions in Lymnaea stagnalis AChBP (SEQ ID No. 2) have been identified. Consecutive regions have at least every second residue involved in contacts with the other monomer. Contacts have been defined as 2 atoms within 4.2 angstrom distance in 2.7 Angstrom structure. The primary contact regions in mature AChBP (residues from A contacting B) are 15-21 , 44-47, 85-87, 91-94, 122-124,143-146, 149, 185-187 and the complementary contact regions (from B contacting A, (identical to residues on A contacting E) are 3-4, 7-8, 11 , 37-39, 53, 75-77, 96-104, 114-118, 163-170; see also Figure 14.

Thus, in one preferred embodiment the drug of the present invention interacts with a ligand-gated receptor comprising a pentamer with monomers A to E, wherein the drug binds to one or more primary contact regions of a monomer (residues from A contacting B) defined by amino acid residues 15 to 21 , 44 to 47, 85 to 87, 91 to 94, 122 to 124, 143 to 146, 149, 185 to 187 of SEQ ID No. 2 and/or to one or more of the complementary contact regions of the other monomer (from B contacting A, (identical to residues on A contacting E) defined by amino acid residues 3 to 4, 7 to 8, 11 , 37 to 39, 53, 75 to 77, 96 to 104, 114 to 118 and 163-170 of SEQ ID No. 2; or to one of the contact regions identified in Figure 14; or to the corresponding contact regions of the monomers of a ligand-gated ion channel. Preferably, the ligand-gated ion channel is the nicotinic acetylcholine receptor and the order of the monomers is αγαδβ.

Any available method may be used to construct such model from the crystallographic and/or amino acid sequence data disclosed herein or obtained from independent analysis of crystalline AChBP proteins or other water-soluble ligand-binding proteins of the present invention. Such a model can be constructed from available analytical data points using known software packages such as HKL, MOSFILM, XDS, CCP4, SHARP, PHASES, HEAVY, XPLOR, TNT, NMRCOMPASS, NMRPIPE, DIANA, NMRDRAW, FELIX, VNMR, MADIGRAS, QUANTA, BUSTER, SOLVE, 0, FRODO, RASMOL, CNS , REFMAC, ARP/WARP, XTALVIEW and CHAIN. The model constructed from these data can then be visualized using available systems, including, for example, Silicon Graphics, Evans and Sutherland, SUN, Hewlett Packard, Apple Macintosh, DEC, IBM, and Compaq. The present invention also provides for devices such as a computer system which comprises the model of the invention and hardware used for construction, processing and/or visualization of the model of the invention. Further embodiments provide a computer system comprising computer hardware and the model of the present invention. The study of the interaction of the candidate species with the model can be performed using available software platforms, including QUANTA, RASMOL, O, CHAIN, FRODO, INSIGHT, DOCK, MCSS/HOOK, CHARMM, LEAPFROG, CAVEAT (UC Berkley), CAVEAT (MSI), MODELLER, CATALYST, XTALVIEW and ISIS. Computer readable media such as floppy discs, CD ROMs, tapes, and any other storage or processing means comprising crystallographic and/or nucleotide/amino acid sequence data disclosed herein or obtained from independent analysis of crystalline AChBP proteins or other water-soluble ligand-binding proteins of the present invention are subject of the present invention as well. Any one of the mentioned means and devices can advantageously be used for modeling an antagonist/inhibitor or agonist/activator of a ligand-gated receptor. Furthermore, the present invention relates to the construction of theoretical three dimensional (3D) models of ligand-binding domains of ligand-gated ion channels by computer-assisted molecular modeling using the X-ray coordinates of the water- soluble ligand-binding proteins of the invention. These 3D models can correspond either to the entire ligand-binding domain (-220 to 240 extracellular amino acids) or may be limited to the ligand-binding site.

The concept of using 3D structures of the mollusc ligand-binding proteins for molecular modeling and tool for structure prediction of for example mammalian, in particular human ligand-gated ion channels gains support from the observation that the ligand-binding domain of vertebrate glutamate receptor channels and bacterial periplasmic substrate-binding proteins (PBPs) share similar 3D structures despite the very low sequence similarity between ionotropic glutamate receptor subunits and the PBPs that were used as templates (12%); for review see Paas et al. TiPS 21 (2000), 87- 92 and refemces cited therein

Thus, on the basis of a computer-assisted molecular modeling, optionally supplemented by for example functional studies of site-specific mutants, the crystal structure of the ligand-binding domain of ligand-gated ion channels and theoretical 3D models of these domains can be predicted. In turn, these models can be used for structure assisted drug design. The predicted models may be further refined, for example by monitoring the effects of mutations of amino acid residues that are probably located in the ligand-binding site on (1) agonist-elicited channel activation and desensitization, (2) inhibition of channel activity by various competitive receptor antagonists; or (3) the binding of various ligands. Experimental setups for analyzing such effects are known to the person skilled in the art, see also the documents cited for functional assay systems of ligand-gated ion channels.

Thus, the embodiments of the present invention enable various possibilities for identification and modeling new ligands of ligand-gated ion channels as well as modifying the ion channels themselves. Accordingly, the present invention relates to the use of the above described polynucleotides, proteins, dimers and pentamers, ligand-gated ion channels, vectors, host cells, antigens, antibodies, oligonucleotide probes, crystals, their structural coordinates and methods for screening or profiling putative ligands of ligand-gated receptors. Methods for the lead generation in drug discovery using proteins and detection methods such as mass spectrometry (Cheng et al. J. Am. Chem. Soc. 117 (1995), 8859-8860) and some nuclear magnetic resonance (NMR) methods (Fejzo et al., Chem. Biol. 6 (1999), 755-769; Lin et al., J. Org. Chem. 62 (1997), 8930-8931).

The newly identified drug obtained by a method of the present invention, i.e. an antagonist/inhibitor or agonist/activator can be used for the preparation of a pharmaceutical composition for the treatment of a ligand-gated ion channel mediated or related disorder. Such disorders are well know to the person skilled in the art. For example, possible applications of agonist and antagonists to nAChRs are based on their participation in complex functions such as attention, memory, and cognition, and their involvement in the pathogenesis of certain neuropsychiatric disorders (Alzheimer's and Parkinson's diseases, Tourette's syndrome, schizophrenia, depression, etc). For the majority of these disorders, the use of nAChRs' agonists may represent either a prophylactic (esp. for Alzheimer's and Parkinson's diseases) or a symptomatic treatment; for review see for example Mihailescu and Drucker- Colin, Arch. Med. Res. 31 (2000), 131 -144. The medicinal chemistry and molecular biology of GABA-activated ligand-gated ion channels also in terms of agonist and antagonist structural profiles is described in Chebib et al., J. Med. Chem. 43 (2000), 1427-1447.

Glycine receptors and disorders of glycinergic neurotransmission are extensively reviewed in Rajendra et al., Pharmacol. Ther. 73 (1997), 121 -146 and Barry et al., Clin. Exp. Pharmacol. Physiol. 26 (1999), 935-936. The central role of 5-HT3 receptor in CNS disorders and 5-HT3 receptor antagonists are described in Bloom and Morales, Neurochemical Research 23 (1998), 653-659 and Higgins and Kilpatrick, Expert Opin. Invest. Drugs 8 (1999), 2183-2188.

In one embodiment, the antagonist/inhibitor is or is derived from a protein, an antigen, antibody or from a toxin of the ligand-gated ion channel. Likewise, the agonist activator can be derived from a protein, an antigen, antibody or from a toxin of the ligand-gated ion channel. Possible starting points comprise for example peptide toxins, e.g., conotoxin (IMl) and alpha bungarotoxin, lophotoxins

(Bippinatins), tubocurarine, decamethonium, alpha-cobratoxin, epibatidine, acetylcholine, choline, nicotine, carbachol, serotonin or GABA. The structure of these molecules together with that of the crystal of the target ligand-binding domain can be used to model the compound and elucidate side chains, functional groups etc. which may be added, deleted or modified in order to improve for example affinity and/or specificty of the drug or for example make a drug which acts on a different target non-reactive with a certain ligand-gated ion channel.

In a preferred embodiment for the uses according to the present invention, the ligand-gated ion channel is the nicotinic acetylcholine receptor and said mediated or related disorder is Tourette's syndrome, Alzheimer's disease, addiction to nicotine or schizophrenia.

As mentioned herein before, this is the first time it could be shown that water-soluble ligand-binding proteins exists in molluscs, which closely resemble the ligand-binding domain of ligand-gated ion channel of higher mammals. It is expected that similar ligand-binding proteins exist in other molluscan species or even in the lineage the Mollusca, Protostomia, Coelomata, Bilateria, Eumetazoa, Metazoa, Fungi/Metazoa group. Accordingly, the present invention also relates to the use of a ligand of a ligand-gated ion channel for identifying and isolating a water-soluble ligand-binding protein from such species, preferably from a mollusc. Preferably, the ligand used for the isolation of the protein is -bungarotoxin. The water-soluble ligand binding proteins obtainable from these organisms as well as derivatives that can be made in accordance with the teaching present herein are also subject of the present invention.

Furthermore, for the first time the crystal structure of a nicotinic binding site has been revealed. This crystal structure shows that the molluscan AChBP is a homolog of the LGIC superfamily ligand binding domains. It reveals the Ig-topology, the location of the binding site at the subunit interface, the position of the MIR and the extensive data on the nicotinic ligand binding residues. Importantly, it gives important new information about the exact fold and the arrangement of the nicotinic ligand-binding site in three dimensions. It shows the presence of a second pocket that has been noticed by EM analysis. Furthermore, it clarifies the arrangement of subunits by showing the relative positioning of the principal and complementary part of the ligand-binding site. It provides an explanation of the role of the LGIC superfamily conserved residues in stabilizing the monomer structure by the formation of hydrophobic cores and packing of secondary structure elements and it makes clear how the pentamers are built up, and how weakly the pentamer interfaces are conserved between LGICs.

This structure can be used for the numerous drug-design studies that are targeting the LGIC superfamily. The general structural knowledge on its folding will be applicable to the GABA, serotonin (5HT₃) and glycine receptor fields. It will help to understand their ligand-binding characteristics and could thus have impact on development of e.g. anti-emetics aimed at the 5HT₃ receptor or the mood-defining drugs that target the GABA receptors. However, the availability of a three- dimensional description of the nicotinic ligand-binding site will be especially relevant for the design of new drugs against Alzheimers' disease, epilepsy and the addiction to smoking which have the neuronal nicotinic receptors as their targets.

Many embodiments and the examples feature the acetylcholine-binding protein (AChBP) of the invention and the embodiments generally described herein are preferably related to the nicotinic acetylcholine receptor (nAChR), more preferably to the alpha subunit, and most preferably to the alpha 7 subunit. However, it should be understood that all embodiments equally apply to the other water-soluble ligand- binding proteins and generally to the ligand-gated ion channels mentioned herein. For example, the crystal structure of the AChBP can be used to model new ligands for the acetylcholine receptor, preferably such with inhibiting or stimulating action on the acetylcholine receptor. Likewise, it is possible to identify and model new ligands for other ligand-gated ion channels (including glycine, GABA and serotonin receptor) with inhibiting action. Such ligands may for example prevent correct assembly of ligand gated ion channels. Preferably such ligands prevent correct assembly of specific sub types of ligand gated ion channels. On the other hand, ligands can be identified and modeled that promote correct assembly of ligand gated ion channels, preferably of specific sub types of ligand gated ion channels. As mentioned before, the methods of the present invention also allow modeling inhibitors for the non- specific binding site of ligand gated ion channels.

In addition, it is possible to predict and create mutants and chimeras of AChBP with modified assembly behaviour, modified ligand binding behavior such as with increased resemblance of the binding site to the acetylcholine receptor subtype on the primary binding site and generally with increased resemblance to particular ligand-gated ion channels in activity and conformational changes. In view of the closest relationship between AChBP and the acetylcholine receptor it is particular preferred to create mutants and chimeras with increased resemblance of the binding site to the acetylcholine receptor subtype on the secondary binding site. However, the prediction and creation of mutants and chimeras with increased resemblance of the binding site to other ligand gated ion channels subtype on the primary binding site or on the secondary binding site are envisaged as well.

These and other embodiments are disclosed and encompassed by the description and Examples of the present invention. Further literature concerning any one of the antibodies, methods, uses and compounds to be employed in accordance with the present invention may be retrieved from public libraries and databases, using for example electronic devices. For example the public database "Medline" may be utilized which is available on the Internet, for example under http://www.ncbi.nlm.nih.gov/PubMed/medline.html. Further databases and addresses, such as http://www.ncbi.nlm.nih.gov/, http://www.infobiogen.fr/, http://www.fmi.ch/bioIogy/research_tools.html, http://www.tigr.org/, are known to the person skilled in the art and can also be obtained using, e.g., http://www.lycos.com. An overview of patent information in biotechnology and a survey of relevant sources of patent information useful for retrospective searching and for current awareness is given in Berks, TIBTECH 12 (1994), 352-364.

This disclosure may best be understood in conjunction with the accompanying drawings, incorporated herein by references. Furthermore, a better understanding of the present invention and of its many advantages will be had from the following examples, given by way of illustration and which are not intended as limiting.

Unless stated otherwise in the examples, all recombinant DNA techniques are performed according to protocols as described in Sambrook et al. (1989), Molecular Cloning : A Laboratory Manual. Cold Spring Harbor Laboratory Press, NY or in Volumes 1 and 2 of Ausubel et al. (1994), Current Protocols in Molecular Biology, Current Protocols. Standard materials and methods for plant molecular work are described in Plant Molecular Biology Labfase (1993) by R.D.D. Croy, jointly published by BIOS Scientific Publications Ltd (UK) and Blackwell Scientific Publications (UK).

Brief description of the drawings

Figure 1 : Clustal X (1.8) multiple sequence alignment of AChBP amino acid sequences. The AChBP alignment was made using "ClustalX_1.8" (Thompson et al., Nucleic Acids Research 24 (1997), 4876-4882. The subsequent alignment was further processed using "Genedoc" version

2.5.000 (Nicholas et al. (1997) Genedoc a tool for editing and annotating multiple sequence alignments). Identical amino acids are indicated with "^*", equivalent amino acid with ":", and similar amino acids with ".". Glycosylation sites are Asn 66 for L-AChBP and Asn 21 and 26 for B-AChBP in the amino acid sequence of the respective mature AChBP SEQ ID No. 2 and 4, and 6 and 8, respectively.

Figure 2: Hydrophobicity plots of the mature AChBP amino acid sequences. The B&L-AChBP hydrophobicity plots were made using "Protein sequence analyses" according to the method described in Kyte and Doolite (J.

Mol. Biol. 157 (1982), 105-132). 2A: L-AChBP_T1 (SEQ ID No. 2), 2B: L-AChBP_T2 (SEQ ID No. 4), 2C: B-AChBP_ T1 (SEQ ID No. 6), 2D: B-AChBP„T2 (SEQ ID No. 8). Figure 3: Clustal X (1.8) multiple sequence alignment of AChBP amino acid sequences with the amino acid sequences of the ligand-binding domains of the ligand-gated receptors nAChR- 7, GABA_AR-β1 , 5- HT3R and GlyR-α1. Sequence alignment and processing was performed as described for Figure 1. The accession numbers of the amino acid sequences used for the alignment are as follows: Human alphal: Human alpha7: Y08420; Human 5HT3: CAA06442; Human GlyR_alpha1 : S12382; Human GABAAJDI : NP_000797. A similar sequence alignment can be performed with the corresponding rat sequences (ratnAChRa7_Q05941 , rat5HT3R_P35563, ratGABARb1_P15431 , ratGlyRa1_p24524) which will give substantially similar if not identical results.

Figure 4: Clustal X (1.8) multiple sequence alignment of AChBP amino acid sequences with the amino acid sequences of nAChRs. Sequence alignment and processing was performed as described for Figure 1. The accession numbers of the amino acid sequences used for the alignment are as follows: Human alphal : ACHUA1 ; Human alpha2: AAG23253; Human aipha3: A53956; Human alpha4: P43681 ; Human alphaδ: P30532; Human alphaδ: Q15825; Human alpha7: Y08420; Human alphaθ: CAB65091. A similar sequence alignment can be performed with the corresponding rat sequences (ratnAChRa7_Q05941 , mAChRa9_P43144, rnAChR2_P1238, rnAChRa3_P04757, mAChRa4_P09483) which will give substantially similar if not identical results.

Figure 5: Clustal X (1.8) multiple sequence alignment of AChBP amino acid sequences with the amino acid sequences of nAChRs alpha 1 and 7. Sequence alignment and processing was performed as described for

Figure 1. The accession numbers of the amino acid sequences used for the alignment are as follows: Human alphal : ACHUA1 ; Human alpha7: Y08420. A similar sequence alignment can be performed with the corresponding rat sequence ratnAChRa7_Q05941 which will give substantially similar if not identical results.

Figure 6: The pentameric structure of AChBP. a In this schematic representation each monomer has a different grey level. Subunits are labeled anticlockwise, with A-B, B-C, C-D, D-E and E-A forming the plus and minus interface side, with the principal and complementary ligand- binding sites respectively (ball-and-stick representation), b Viewing the AChBP pentamer perpendicular to the five-fold axis. The equatoπally located ligand-binding site (ball-and-stick representation) is highlighted only in the A (light) and B (dark) interface.

Figure 7: The AChBP monomer. Ribbon representation of the AChBP monomer. The secondary structure starting from the N-terminus (top) towards the

C-terminus (bottom). The monomer is viewed towards the center of the pentamer. In the nAChR, the top would correspond to the N- terminus of the ligand binding domain, pointing towards the synaptic cleft, while the C-terminus would be entering the membrane at the bottom, continuing into the transmembrane domain. The AChBP monomer is built up mainly of β-strands, except for an N-terminal (- helix. It contains 14 β-strands that are organized in the two antiparallel β-sheets, with an immunoglobulin topology. However, in contrast to the classical immunoglobulin fold, the AChBP β-sheets are rotated against each other, forming a small pocket, as visible in Figure 6.

Figure 8: The ligand-binding site at dimer interface. Ribbon representation of two neighboring AChBP monomers. Monomer A is shown in grey and monomer B in dark grey. The ligand-binding site is located at the interface between two monomers. As predicted for the nAChRs, the acetylcholine binding site in AChBP occurs at the interface between two neighboring subunits. Similar to the model proposed for the nAChRs, the ligand-binding site is asymmetric, formed mainly by aromatic residues. Residues from mature AChBP monomer A (TyrA89, TrpA143, TyrA185, CysA187, CysA188 and TyrA192) form the principal component, while residue TrpB53 from monomer B creates the complementary part of the ligand-binding site. There are five identical ligand-binding sites in the AChBP pentamer, similar to the homomeric α7 neuronal receptor.

Figure 9: The ligand binding site. Stereo figure showing the ligand binding site in AChBP, at the interface of two monomers. Residues from mature AChBP monomer A (TyrA89, TrpA143, TyrA185, CysA187, CysA188 and TyrA192) form the principal component, while residue TrpB53 from monomer B creates the complementary part of the ligand-binding site with with additional residues ArgBl04, LeuB112 and MetB114. There are five identical ligand-binding sites in the AChBP pentamer, similar to the homomeric α7 neuronal receptor.

Figure 10: Multiple sequence alignment of AChBP amino acid sequences with indication of secondary structure and solvent accessibility derived from the crystal structure. Alignment of the four molluscan AChBP sequences, with secondary structure and solvent accessibility of the Lymnea stagnalis AChBP-1 indicated from the crystal structure. The Figure was prepared with ESPript (Gouet et al., Bioinformatics. 15 (1999), 305-308), using DSSP (Kabsch and Sander, Biopolymers. 22

(1983), 2577-2637). Under the alignment the solvent accessibility is indicated, white most buried, dark blue most exposed, according to ESPript defaults (blue A> 0.4, cyan 0.1 <A<0.4, white A<0.1 ).

Figure 11 : Sequence alignment of AChBP with LGICs. The alignment shows only the N-terminal domain of the LGIC subunits and is based on a multi- sequence alignment of 92 full-length LGIC sequences. Abbreviations used, H and Tea, stand for human and Torpedo californica. Secondary structure elements (α: -helix, β: β-strand, η: 3₁₀-helix) are indicated above the sequence, in accordance with Fig 12a. AChBP shares 23% sequence identity with the ligand-binding domain of human α₇. The LGIC conserved residues (bold, grey background) are displayed. Beginning and end of the Cys-loop are indicated by a "^*". Nicotinic receptor ligand-binding residues on the principal and complementary side are indicated. Figure 12: Overview of the AChBP monomer structure, a Stereo representation of the AChBP monomer as viewed from outside the pentameric ring.

Disulfide bridges are indicated in ball-and-stick representation. In a complete ion-channel the N-terminus would be pointing towards the synaptic cleft, while the C-terminus would enter the membrane at the bottom, continuing into the first transmembrane domain, b Topology diagram of the AChBP monomer. For comparison with Ig-folds the strands have been labeled a-g, showing the additional strand (b') and hairpin (f-f). In this structure, strands have been labeled β1-β10 with loops (or turns) L1 -L10 preceding each strand with the same number.

The β5 strand is broken (β5-β5') with internal loop L5', βδ also has a small break, but is shown continuously; (see Fig. 11 ). The precise beginnings and ends of strands may change slightly with increasing resolution, but the topology seen here will be highly conserved across the entire family of LGICs.

Figure 13: The ligand-binding site, a Stereo representation of the ligand-binding site in ball-and-stick representation, showing the contribution of the principal A B (TrpA143/α_!Trp149) and C (TyrA185/α yrl 90, CysA187/^Cysl 92, CysA188/ct Cysl 93, TyrA192

/αιTyr198) and the complementary D (TrpB53/γTrp55, GlnB55/γGlu57) , E (ArgB104/γLeu109, ValB106/γTyr111 , LeuB112/γTyr117, MetB1 14 /γLeu119) and F (TyrB164) 'loops', b Stereo view of the electron density map displaying a HEPES buffer molecule in the ligand-binding site. This experimental density (contoured at 1 σ) is derived from cross-crystal averaging, c Location of the principal ligand-binding residues on the monomer, d Location of the complementary ligand- binding residues on the monomer, (orientation as in Figure 6b)

Figure 14: Dimer interface a Stereo figure of the dimer interface. Representation of the interface residues (ball-and-stick) on a schematic secondary structure figure. The figure shows the plus face of subunit A and the minus minus face of subunit B b Dimer interface interactions. Note that due to the low conservation of these interfaces (Fig. 11) the actual interactions will not be conserved in any LGIC interface, but that in all receptors the topological regions are likely to form the interface. Figure 15: Conservation in the LGIC superfamily. Conserved residues are indicated on the top, middle and bottom respectively on the monomer as viewed from the central pore. The hydrophilic conserved residues are indicated in dark. Conserved residues are indicated as viewed from the central pore. Hydrophobic Cluster I: residues 6, 10, 63, 65,

71 , 81 , 105, 111; Cluster ll: residues 20, 27, 29, 31 , 58, 82, 84, 86, 140, 150, 152, 195; Cluster III: residues 33, 35, 38, 41 , 48, 52, 125, 138, 171 , 173, 199, 201. The hydrophilic conserved residues: Asp60, Asp85, Asn90, Gly109, Cys123, Cys136, Lys203. Conserved residues in the ligand binding site: 106, 145, 192. These three and Lys203 are the only conserved residues without structural role in the monomer. Note how very few conserved residues are at the surface. Within the LGIC family the Cys-loop residues are also highly conserved; see bottom, left.

EXAMPLES

EXAMPLE 1 : Isolation of Lymnaea AChBP from the CNS, determination of mass and N-terminal protein sequence

Isolation: 80 CNS of Lymnaea were homogenized in lysis buffer (PBS [16 mM Na2HP04, 4 mM NaH2Pθ4, pH 7.4; 150 mM NaCl] 0.5% Nonidet P-40; 0.1 % triton, 0.2% tween-20) containing 1 ug/ml aprotinin, 10 ug/ml benzamidine, 0.5 ug/ml leupeptin, 24 ug/ml pefabloc. The CNS lysate was cleared by triplicate centrifugation at 12,000x g for 5 min. Streptavidin-coated magnetic beads (Dynal, Oslo), 5 mg, were saturated with α-bungarotoxin conjugated to Biotin (4 ug) (Molecular Probes, Oxford, UK). These beads were washed in PBS to remove excess α-bungarotoxin, then added to the cleared CNS lysate, and incubated for 1 h. After this, beads were washed 3 times in PBS to remove unbound protein. A control reaction without α- bungarotoxin was performed. Proteins bound to α-bungarotoxin were allowed to elute off in 10 μl of PBS containing 10-4 M nicotine for 1 h.

Mass determination: The eluent was separated on a microcolumn LC system was similar to that described previously (Hsieh et al.; Anal. Chem. 70; 1998; 1847-1852). A commercial syringe pump (Perkin-Elmer /ABI, model 140B) was used to deliver a flow rate of 20 μl /min to the column. After loading of sample to the column the flow rate was dropped to 10 μl /min. The eluent was then switched from 0.2% acetic acid to 0.2% acetic acid/ 60% acetonitril in 1 min. Electrospray mass spectra in MS mode were acquired on a Micromass Q-TOF quadropole time-of-flight mass spectrometer equipped with a Z-spray atmospheric pressure ionization source. Protein sequence analvsis: For sequence analysis α-bungarotoxin binding protein was extracted using the same procedure, now followed by SDS-PAGE and Western Blotting on PDVF membrane. Sequence analysis was performed with Edman degradation of the 24 kDa blotted protein (apparent MW) using a protein sequencer (ABl, Perkin Elmer).

EXAMPLE 2: Cloning the Lymnaea AChBP cDNA sequence: PCR and screening of a cDNA library PCR cloning: A degenerate oligonucleotide was synthesized based on the amino acid sequence LDRADILYNI (SEQ ID No. 10), residues 1-10, of AChBP, (5'- CGGATCCGA(TC)(AC)GIGC(GATC)GA(TC)AT(ATC)(TC)T(GATC)TA(TC)AA(TC)A T-3'; SEQ ID No. 11), containing a BamHI restriction site, and used in combination with a primer on the IZAPII lambda vector. PCR was performed on a I2AP II cDNA library of the Lymnaea CNS, in a 100 μl reaction volume with 1.0 unit of Super Taq DNA polymerase (Boehringer Mannheim, Germany) in a DNA thermal cycler (Perkin- Elmer Cetus, CT) using 45 cycles of (94 °C, 20 sec; 53 °C, 30 sec; and 72 °C, 1 min. Amplified cDNA was digested with BamHI and EcoRI, separated on agarose gel, and a product of -900 bp was cloned and sequenced.

Library screening: Approximately 20,000 clones of the amplified lambda ZAP II CNS cDNA library were plated at a density of 10⁵ pfu/400 cm² and absorbed to charged Nylon membranes (Boehringer Mannheim, Germany). The AChBP PCR product was used as a random primed probe, labeled with [alfa32p]dATP (specific activity >10⁹ cpm/mg). Membranes were hybridized in 6x SSC (1x SSC: 0.15 M NaCl and 0.015 M Na-citrate), 0.2% SDS, 5x Denhardts and 10 ug/ml herring sperm DNA at 65 °C for 18 h. The filters were washed in 0.2x SSC, 0.2% SDS, at 65 °C for 30 min, and autoradiographed. Four individual cDNA clones were in vivo excised, and sequenced using dideoxy chain termination in both orientations. Two types of sequence were obtained, named L-AChBP_T1 and L-AChBP_T2. The signal sequences were determined with "SMART", Simple Modular Architectur Research Tool (V3.1); see Schultz et al., Proc. natl. Acad. Sci. USA 95 (1998), 5857-5864 and Nucleic Acids Res. 28 (2000), 231 -234. In case of L-AChBP_T1 (SEQ ID No. 2) the prediction could experimentally be confirmed.

EXAMPLE 3: Lymnaea AChBP-related sequences: cloning of the Bulinus truncatus cDNAs Total RNA was isolated from Bulinus brain ganglia (CNS), and reverse transcribed into hexanucleotide primed cDNA. Two degenerate oligonucleotides, directed to the Lymnaea AChBP TI sequence, forward primer: 5'-

GCGAATTCGAYACIGARWSIGGNGCNACNTG-3' (SEQ ID No. 12), reverse primer: 5'-GCGAAGCTTCRTCYTCRTAIGCYTCNGCRCARC-3' (SEQ ID No. 13), were used to amplify AChBP-related sequences. PCR was performed on one animal equivalent of CNS cDNA using 150 pmole of each primer under standard conditions for 45 cycles (94'C, 20 sec; 54' C, 30 sec; 72 'C, 1 min). Amplified cDNA was EcoRI/Hindlll digested, cloned into EcoRI/Hindlll digested pBluescript, and sequenced. The ORFs of the obtained sequences showed a Bulinus AChBP, sequence-related to Lymnaea AChBP, named B-AChBP_T1. This partial cDNA was used to screen a Bulinus brain cDNA library using the same hybridization protocol as described for the cloning of the Lymnaea cDNAs, and yielded two cDNA clones, encoding B-AChBP_T1 and B- AChBP_T2. Sequencing of the cDNAs was performed in both orientations. EXAMPLE 4: The production of L-AChBP-T1 and -T2 and B-AChBP-T1 and -T2 in the yeast Pichia pastoris and functional characterization Production of recombinant AChBP:

In order to produce L-AChBP_T1 and T2 and B-AChBP_T1 and T2 as recombinant proteins in the Pichia pastoris expression system (Pichia Expression Kit version 3.0, Invitrogen), the DNA sequence encoding the mature form of these proteins (see sequence files) was cloned into the pPIC9 expression vector (Invitrogen). The mature sequences of L-AChBP_T1 , T2 and B-AChBP_T1 and T2 were PCR amplified (using Pfu-taq DNA polymerase (Stratagene) in order to avoid introduction of errors into the sequence due to PCR) and restriction sites were added to the primers to allow rapid pPIC9 compatible cloning. The amplified sequence of mature AChBP L-AChBP_T1 was EcoRI inserted into pPIC9, whereas L-AChBP_T2 and B-AChBP_T1 and T2 were Xhol/EcoRI inserted into pPIC9 (the alpha-mating factor cleavage site was fully reconstructed after Xhol digestion).

Constructs with and without an additional C-terminal His-tag (SRGHHHHHH (SEQ ID No. 14) in the case of L-AChBP_T1 , EFKDDDDKHHHHHH (SEQ ID No. 15) otherwise) were generated for each of the AChBP (sub)types. The AGhBP/pPIC9 constructs were amplified in E. coli DH5αF and isolated and purified using the plasmid Maxi Kit (Qiagen). Due to the engineered cleavage site at the N-terminus of the amino acid sequence four additional amino acids (EAEA, SEQ ID No. 16) will precede the N-terminus of the original mature protein. Prior to transfection into Pichia pastoris the constructs were linearised (for protocol see supplier's manual; Pichia Expression Kit version 3.0, Invitrogen) and subsequently purified by phenol/chloroform extraction, and ethanol precipitation. Approximately 5 μg of each of the linearised constructs was transformed into freshly prepared electro-competent Pichia pastoris cells and plated onto MD plates (for protocol see supplier's manual; Pichia Expression Kit version 3.0, Invitrogen corporation). Electrocompetent Pichia pastoris cells were aquired according to the protocol provided by Invitrogen. Plates were incubated at 30°C until the appearance of Pichia colonies, which were subsequently analysed for the presence of the correct insert by PCR amplification (for protocol see supplier's manual; Pichia Expression Kit version 3.0, Invitrogen). Colonies containing an homologous recombination with the Pichia genome, carrying the AChBP sequence, were grown in 25 ml of BMGY for 1 -2 days (30°C; rotation at 250rpm), after which the cells were centrifuged (10 min., 1500g) and the cell pellet was resuspended into 10 ml of BMMY. Growth (30°C, 250rpm) was continued for an additional 4 days (day 3-6), during which the expression of AChBP was induced by the addition of 100% methanol (1 % of total culture volume) once every 24 hours. At day seven the culture was centrifuged (15 min.; 2000g; 4°C) and the medium was collected. The AChBP expression level of the various cultures was determined by the analyses of a fraction of the collected medium with SDS-polyacrylamide gel electrophoresis (see suppliers manual; Pichia Expression Kit version 3.0, Invitrogen). The cultures that yielded the highest level of AChBP expression were selected and stored as glycerol stocks. Recombinant AChBP that contained a C-terminal His-tag was isolated and purified from the Picha pastoris medium using Talon metal affinity resin (according to protocol as described within the user manual; Clontech laboratories Inc.). The protein concentration was. subsequently analysed using SDS-polyacrylamide gel electrophoresis and reference marker proteins. Polyclonal antibodies have been raised succesfuily to the recombinant L-AChBP_T1 and B-AChBP_T1 proteins in Balb-C mice. Immune-sera were obtained without crosslinking of the proteins.

Binding characteristics of AChBP:

First the binding curve of α-Bungarotoxin to His-tagged AChBP was determined, and an affinity of 3.5 nM was calculated. Using α-Bungarotoxin in a competitive binding assay ligands of several types of ligand-gated ion channels were then tested on His- tagged AChBP, i.e., ACh, serotonin, GABA, glycine, and glutamate. Both ACh and serotonin did compete with α-Bungarotoxin binding at 4.2 mM and 269 mM, IC50s respectively. GABA, Glycine and glutamate did not compete for binding with α- Bungarotoxin. Thus, as predicted by the primary sequence and by subunit structure also the ligand-binding characteristics of AChBP resembled that of a nAChR.

In a second series of competitive binding assays the ligand binding characteristics of AChBP were studied in more detail, now using various agonists and antagonists of the AChRs. Nicotine a classical agonist of the nAChRs, is a high affinity ligand of His- tagged AChBP (IC50 98 nM). Epibatidine, a high affinity agonist of the nAChRs, also binds with high affinity to His-tagged AChBP (IC50 1.4 nM), which is even higher than the 58 pM affinity of epibatidine reported for the nAChR (Badio, Mol. Pharmacol. 45 (1994), 563-569). Other cholinergic agonists bind with a lower affinity e.g., decamethonium, carbachol, and choline respectively with IC50s of 4.1 μM, 43 μM. and 190 μM. Summary of affinities indicated in Table 2. Table 2

Competition-binding of typical antagonists of the nAChRs, e.g., tubocurarine and α- Bungarotoxin, have a high affinity for His-tagged AChBP, respectively IC50s of 93 nM and 2.6 nM. The cholinergic antagonist succinylcholine has a very low affinity for His-tagged AChBP (IC50 7.9 mM). Interestingly, also muscarinic receptor antagonists bind to His-tagged AChBP with relatively high affinity, e.g., the muscarinic allosteric modulator gallamine (IC50 39 nM), and the muscarinic antagonist atropine (IC50 5.3 mM). Physotigmine which is a known blocker of acetylcholinesterase and is also an antagonist of the nAChR, binds to His-tagged AChBP with an IC50 of 1.3 mM. Finally, Bipinnatin-B was tested, a synthetic form of the coral lophotoxin on AChBP (Groebe and Abramson, J. Biol. Chem. 270 (1995), 281-286). Bipinnatin-B is a general blocker of nAChRs and is known to covalently bind to Tyr-190 of the α subunits (Abramson, J. Biol. Chem. 263 (1988), 18568-18573). His-tagged AChBP was incubated with the toxin, and the mass of the protein increased with 430.1 Da, corresponding well to the calculated mass of Bipinnatin-B of 431 Da, indicating that the toxin also binds to Tyr-184 in His-tagged AChBP.

EXAMPLE 5: Expression and purification of recombinant AChBP for crystallization

The AChBP_T1 protein from Lymnea stagnalis (AChBP) was overexpressed in Pichia pastoris GS1 15 strain using the AOX1 gene expression system from Invitrogen. Media and methods used for AChBP expression are also described in Invitrogen manual Pichia Expression Kit. For long term storage the transformants were grown overnight in YPD medium at 30°C. YPD or Yeast Extract Peptone Dextrose medium

1 % yeast extract (Difco)

2% peptone (Difco)

2% dextrose (glucose) (Merck) The cells were harvested and suspended in YPD medium containing 15% glycerol at final OD600 of -50. The cells were frozen in a dry ice/ethanol bath and stored in the freezer (Revco) at -80°C. Normally, the expression of AChBP started with plating the cells from the glycerol stock on MD plate.

MD or Minimal Dextrose Medium 1.34% YNB (yeast nitrogen base w/o amino-acids) (Difco)

4x10-5 % d-biotin (Sigma)

1 % dextrose

For plates add 15g of agar (Difco)

The plate was stored in the incubator (Heraeus) for 3-4 days at 30°C. A single colony was picked from the plate and inoculated in 150 ml baffled flask (Nalgene) containing

25 ml of BMGY medium.

BMGY or Buffered Glycerol-complex Medium

1 % yeast extract

2% peptone 100 mM potassium phosphate (pH 6.0) (Merck)

1.34% YNB

4x10-5 % d-biotin

1 % glycerol (Merck)

The culture was placed into the shaker (New Brunswick) and left to grow overnight rotating at 250 rpm at 30°C. The following day 12.5 ml of the culture was inoculated into 225 ml of BMGY medium in a 1000 ml baffled flask. In order to increase the yield of expressed AChBP a larger number of flasks were used, usually 16. The flasks were placed in the shaker and start-cultures were rotated at 250 rpm at 30°C. After two days the start-cultures were centrifuged for 15 min at 2500 rpm (Sorvall RC3B+. rotor H-6000A) at room temperature. In order to increase the cell mass for bigger protein production, cell pellets of two start-culture flasks were pooled together and resuspended in 200 ml of BMMY medium containing 1% (w/v) casamino acids.

BMMY of Buffered Methanol-complex Medium ^'+ 1% casamino acids

1 % yeast extract 2% peptone

100 mM potassium phosphate (pH 6.0)

1.34% YNB 4x10-5 % d-biotin

0.5% methanol (Merck)

1 % casamino acids (Difco)

The cultures were put back into the shaker (250 rpm, 30°C) and induced for the following 4 days. The concentration of methanol in the medium was kept constant by adding 1% (v/v) methanol to the cultures every 24 hours. After 4 days 100 ml of culture was harvested and the original volume of 200 ml was readjusted by adding fresh BMMY medium with 1 % casamino acids. The remaining cultures were induced for another 4 days. The harvested cultures were centrifuged for 5 min at 4000 rpm (Sorvall RC3B+, rotor H-6000A) and the cell pellet was discarded. The supernatant was first filtered through a 0.22 μm filter (Millipore) to remove any remaining cells and it was concentrated using a Minitan system (Waters/Millipore) with 30kDa cutoff filter (Waters/Millipore). Both the filtration and concentration and were performed at 4°C. Finally, centrifugation at 16000 rpm was done (Sorvall RC5C, rotor SS-34) in order to remove any debris left after the first two steps. The final volume of concentrated sample was -80 ml and it was dialyzed overnight against 2 x 5 I (20 mM Tris [pH 8.0], 150 mM NaCl and 0.02% NaN3) using 15kDa cutoff dialysis membrane

(Spectra/Por) at 4°C. The dialyzed protein solution (-100 ml) was loaded onto an anion-exchange column (POROS 50 HQ, Pharmacia, column volume 8 ml). After the initial wash step of -15 column volumes using loading buffer, a salt gradient of 30 column volumes was run from 150 mM to 1000 mM NaCl. Both solutions contained also 20 M Tris (pH 8.0) and 0.02% NaNβ. The peak of interest eluted at -300 mM

NaCl (conductivity range 16-24 mS/cm). The presence of AChBP was checked by Bio-Rad Protein Assay (Bio-Rad) and SDS-PAGE and the fractions of interested were pooled and concentrated using a Centriprep with a 30kDa cutoff membrane (Amicon). The concentrated sample (volume of 5 ml) was loaded onto a gel filtration column (Superdex 200 HR 16/60, Pharmacia, column volume 120 ml) using 20mM Tris (pH 8.0), 150 mM NaCl and 0.02% NaN3. The protein eluted starting from 60 to

71 ml with peak at -66 ml. The final purification step of the protein was done on an anion-exchange column (MonoQ HR10/10, Pharmacia, column volume 6 ml). The protein was loaded onto the column in the same buffer as eluted from the gel filtration column. The salt gradient used for the column was the identical to the one used for the POROS 50 HQ column. The fractions in the conductivity range 25-27.5 mS/cm were pooled together and dialyzed against buffer containing 50 mM HEPES (pH 7.0) and 0.02% NaN_β. The protein was concentrated up to -20 mg/ml using a Centricon with a 30kDa cutoff membrane (Amicon). The total yield was about 2 mg purified protein per liter of expressed medium. The concentrated protein was stored at 4°C and used for crystallization experiments and biochemical characterization. N-terminal sequencing revealed the presence of EAEAYVEF residues that are part of the plC9- encoded signal sequence, before residue 2. The experimental mass was determined to be 26544 Da (MALDI), which is ~2kDa more than calculated mass based on amino-acid sequence (24649 Da). The difference is assigned to glycosylation of

AChBP at position Asn66 in the mature sequence, confirmed by deglycosylation experiments with N-glycosidase F (Boehringer).

The purification of the first harvest was done separately from the full harvest. They were pooled together prior to the last purification step (anion-exchange chromatography step on MonoQ column). All above mentioned chromatography columns were mounted on an FPLC system (Pharmacia) controlled by the UNICORN system (Pharmacia). All solutions used in the FPLC system were prepared with MilliQ UF+ water, filtered through 0.22 μm filter (Millipore) and degassed.

EXAMPLE 6: Crystallization of the AChBP

All the crystallization experiments were done by vapor diffusion technique in a hanging drop mode using 12 well tray (Nelipak) and siliconized cover slides (Hampton Research). Trays were placed in a sandwich box (Semadeni) and stored at 19°C temperature conditioned room. The initial crystallization attempts were performed using Hampton Crystal Screen I and II (Hampton Research). Drops contained 2 μl of protein (10 mg/ml in 50 mM HEPES [pH 7.0] and 0.02% NaN₃) and 2 μl of reservoir solution. From the first screen it became clear that AChBP makes crystalline precipitate in the presence of CaCI₂ salt. A more detailed screen was made which produced crystals suitable for X-ray analysis. The AChBP crystals appeared in the following conditions: 9-11 % (w/v) PEG 4000 (Hampton Research), 100 mM HEPES (pH 7.0), 50-200 mM CaCI₂ x 6H₂0 and 0.02% NaN₃ or or PEG MME 550 10-18% in the same conditions, with 0.3 mM ZnAcetate as additive. Depending on the batch of the protein used and the CaCI₂ concentration three different crystal forms were found: orthorhombic, tetragonal and monoclinic. Both orthorhombic and monoclinic crystal forms are frequently twinned. Orthorhombic rodlike crystals appeared immediately upon setting up the crystallization experiments (in between first few hours) under high [CaCI₂]. The size of the crystals varied from 0.05x0.05x0.15 to 0.25x0.25x1.0 mm. The crystals diffract X-ray up to 3 A resolution and show high degree of mosaicity (-05-1.2°). They have the symmetry of space group P _ΛZ 2 with cell constants of a= 120.62A, b=137.0lA, c=161.54A with 2 pentamer molecules per asymmetric unit. Tetragonal crystals, squared in shape, grew at lower CaCI₂ concentration, reaching 0.2x0.3x0.35 mm in size. The maximal resolution obtained was 2.7 A with a lower mosaicity (0.5°). They belong to space group P4₂2-|2 space group with cell dimensions of a=b=141.66A, c=120.83A with one pentamer molecule per asymmetric unit. The exact crystallization condition for the tetragonal crystal which was used for refinement of the crystal structure: 11.5% (w/v) PEG 4000, 100 M HEPES (pH 7.0), 150 mM CaCI₂ and 0.02% NaN₃. The third crystal form, monoclinic P2_{1 ;} is very similar in morphology to the orthorhombic crystals with cell dimensions of a=121.lA, b=162.lA, c=139.4A, β=90.13°, containing 4 pentamers per asymmetric unit. This crystals were gave lower resolution data (~ 3.3A resolution). All three crystal forms were used in the structure determination of AChBP.

The resolution limit of diffraction depended very much on the size of the crystals. And the largest crystals diffracted weakly to ~4A resolution when exposed to a conventional rotating anode X-ray source. Therefore, the use of synchrotron radiation was critical for the structure determination. The crystals had to be cryo-protected in order to slow down the damage caused by high intensity synchrotron radiation. The cryo-protection of the AChBP crystal was done in multiple steps. The first steps included the stabilization of crystal by adding the 2 μl of mother liquor (equilibrated reservoir solution) to the drop with the crystal. After 5 minutes 3 μl of stabilizing solution was added to the drop. Normally, the stabilizing solution contained slightly higher concentrations (1-5%) of the components of the original crystallization buffer. As protectant glycerol (Merck) was added, increasing the concentration stepwise from 0% to 30% (v/v). For example, the starting solution contained 15% PEG 4000, 100 mM HEPES (pH 7.0), 150 mM CaCI₂ and 0.02% NaN₃ and the final solution contained 30% (v/v) glycerol in addition to the components just mentioned. The AChBP crystals do not tolerate drastic increase in the glycerol concentrations therefore a gentle but more time consuming approach has to be adopted. The solution around the crystal has to be stepwise exchanged (usually 5% increase of glycerol concentrations) allowing crystals to equilibrate for at least 5 minutes in each glycerol concentration. Once the crystals were equilibrated in stabilizing solution with 30% glycerol they were flash-cooled in liquid nitrogen or in the cryo-stream. In all three space groups AChBP forms a decamer structure with perfect 52 symmetry, where two pentamers contact each other through a calcium-binding site, at the 'top' of the α1 helix. This binding site (Asp2 and Asp5 from two monomers) is not conserved in the LGIC family. In the tetragonal space group the 2-fold of the decamer coincides with a crystallographic two-fold, which leads to pseudocentrosymmetric behavior of the phases at low resolution. In solution the AChBP protein acts as pentamer.

Those of skill in the art will appreciate that the aforesaid crystallization conditions can be varied. Such variations may be used alone or in combination, and include final protein (optionally in complex with a ligand) concentrations between 1 mg/ml and 30 mg/ml; all combinations of AChPB/Iigand to precipitant ratios; use of citrate concentrations between 0 mM and 200 mM; DTT concentrations between 0 mM and 10 mM; and any concentration of beta-mercaptoethanol; pH ranges between 5.5 and 9.5; PEG concentrations between 5% and 25% (w/v); PEG weights between 2000 and 8000; HEPES concentrations between 5 and 500 mM; use of TRIS or other solutions instead of HEPES, and any concentration or type of detergent; any other type of precipitating agent; any other buffer; any temperature between -50 ^SC and 30 ^SC; and crystallization of AChBP or complexes thereof by batch, liquid bridge, or dialysis method using these conditions or variations thereof.

EXAMPLE 7: Structure determination

The crystal structure was determined using the multiwave anomalous dispersion (MAD) technique on a Pb derivative, but non-crystallographic symmetry (NCS) averaging was necessary to obtain interpretable electron density. Collection of native data and heavy-atom derivatives were carried out at the synchrotron beam-lines in Grenoble (ESRF/BM14 and ID14) and Hamburg (DESY/BW7A, BW7B and X1 1 ). The AChBP orthorhombic crystal was soaked in stabilizing solution containing 5 mM trimethylleadacetate (MePb) for 5 days. Data sets were collected at four^' different wavelengths (0.9492A, 0.861 OA, 0.9507A and 0.9499A) and data were integrated and reduced using DENZO/SCALEPACK (Otwinowski and Minor (1997) Processing of X-ray diffraction data collected in oscillation mode. In Methods in Enzymology, Volume 276: Macromolecular Crystallography, part A. C.W. Carter and R.M. Sweet, eds. (New York: Academic Press), pp. 307-326). The program SOLVE (Terwilliger (1997) SOLVE: An automated structure solution for MAD and MIR. Edition 1 .16) found 5 Pb sites which were situated on the interface between two pentamers. The Pb parameters were refined and phases calculated with SHARP (La Fortelie et al. (1997) Advances in MIR and MAD phasing: Maximum-likelihood refinement in a graphical environment, with SHARP. Proceedings of the CCP4 study weekend). Mean figure of merit (FOM) value for 4 wavelengths was 0.45. Search and optimization of 5-fold NCS operators were done using programs NCS6D and IMP (Kleywegt and Jones (1999) Software for handling macromolecular envelopes. Acta Crystallo., D55, 941-944). 10-fold averaging using refined NCS operators in conjunction with density modification by DM (Cowtan (1994) DM: An automated procedure for phase improvement by density modification. In Joint CCP4 and ESF- EACBM Newsletter on Protein Crystallography 31 , 34-38) yielded an interpretable electron density map. However, some parts of the pentamers were still not clearly defined. Therefore, a second MAD experiment was performed on the monoclinic crystals soaked in 10 mM MePb for 5 days. Data were collected for only two wavelengths, at the Pb peak (0.9479A) and remote (0.9498A) wavelength. The processing of the two collected data sets was done with MOSFLM (Leslie (1992) Recent changes to the MOSFLM package for processing film and image plate data. In Joint CCP4 and ESF-EACBM Newsletter on Protein Crystallography, Number 26) and data were scaled with SCALA (CCP4. The CCP4 suite: programs for protein crystallography. Acta Crystallog. D50, 760-763). 10 Pb sites were identified with Solve. The Pb parameters were refined and phases calculated with SHARP in single anomalous dispersion (SAD) mode using data collected at the Pb absorption peak The NCS operators needed for 20-fold averaging were found by NCS6D and improved with IMP. 20-fold averaging and density modification by program DM further improved electron density. The initial model tracing and sequence assignment were done based on the 20-fold averaged electron density with program O (Jones et al., 1991). However, parts of the molecules were not clearly defined. The electron density was further improved doing multi-crystal averaging with DMMULTI (Cowtan, 1994) using amplitudes of tetragonal, orthorhombic and native data sets and experimental phases of the orthorhombic and monoclinic MAD experiments. Initially missing parts became clearly defined and a complete model could be built. The initial atomic model was refined with the program CNS (Brϋnger et al. (1998) Acta Crystallogr. D 54, 905-921) against a maximum-likelihood target without experimental phases contribution using tetragonal native data which extend to 2.7A resolution. Refinement included five-fold NCS restraints, an overall anisotropic B factor and bulk solvent correction. The five-fold NCS restraints were released for the parts of the pentamer that clearly do not follow the five-fold symmetry. The current model contains one pentamer of AChBP consisting of 1035 residues, 14 well-ordered solvent molecules, 5 Ca²⁺ ions, 5 Cl^" ions and 5 Hepes molecules, well-ordered solvent molecules and 5 HEPES molecules. The following residues are not well defined in the electron density: -8-0 (part of α-mating S. cerevisiae signal sequence not native to AChBP EAEAYVEF; SEQ ID No. 21), 125-135, 155-165, 186-191 and 206-210. Electron density is detectable in the ligand-binding site of AChBP. It is presumed that a HEPES molecule could account for this extra electron density based on its chemical properties. HEPES or N-2-Hydroxyethylpiperazine-N'-2-ethanesulfonic acid contains a quaternary ammonium ion similar to ligand such as acetylcholine (ACh) and d-tubocurarine. it has been proposed that the binding of ACh would be mediated by cation-π interaction involving N⁺ and it-systems of aromatic residues present in the binding site of nicotinic acetylcholine receptor. Without intending to be bound by theory it is suggested in accordance with the observation of the present invention that the observed HEPES molecule mimics ligand binding analogous to the binding of natural ligands like ACh in the ligand-binding site.

EXAMPLE 8: More detailed description of the structure determined in Example 7

As described in the previous example, the crystal structure of AChBP was solved using weak Pb MAD data in two crystal forms. The electron density map was improved substantially by cross-crystal averaging of three crystal forms with 20, 10 and 5 copies of the monomer in the asymmetric unit respectively (Table 3).

Table 1 : Data collection statistics

Data set λj_ peak λ₂ remote λ₃ infl. λ₁ peak λ? infl. Native

Space group P 2fo P2 PA_Z2_Λ2

Resol. (A) 3.3/3.4-3.3 3.0/3.1 -3.0 2.7/2.8-2.7

λ (A) 0.9492 0.8610 0.9507 0.9479 0.9498 0.943

Compl. (%) 99.7/99.7 99.6/99.6 99.7/99.7 99.9/99.9 99.5/99.5 97.8/96.5

Mosaicity (°) 0.62 0.43 0.78

Redundancy 3.7/3.8 3.8/3.9 3.7/3.8 3.5/2.2 3.2/2.0 6.5

Eme_rge (%) 7.7/46.8 7.8/45.2 8.3/55.0 5.9/26.1 6.0/32.9 5.9/67.4

llcl 8.7/1.6 8.4/1.7 8.3/1.4 7.7/2.7 6.8/1.5 27.4/2.3 Phasing ISO/ANO ISO/ANO ISO/ANO ISO/ANO ISO/ANO

flcui.is (%) 0.74/0.89 n.a./0.92 0.54/0.94 n.a./0.74 0.66/0.77

Phasing power 0.57/1.2 n.a./1 .06 2.3/0.91 n.a./1.1 0.37/1.22

FOM (overall) 0.45 0.28

The structure was refined at 2.7 A in space group P4₂2₁2, with one AChBP pentamer in the asymmetric unit. Thus, native data (X11) were collected and the Pb-1 data sets (BW7A) at the EMBL/DESY synchrotron in Hamburg and the Pb-2 data sets (BM14) at the ESRF, Grenoble (Table 3). Data were processed with DENZO/SCALEPACK (Otwinowski & Minor, Methods Enzymol. 276, 307-326 1997) (native) or MOSFLM (Leslie, Acta Crystallogr. D. Biol. Crystallogr. 55, 1696-1702, 1999VSCALA (CCP4) (Pb-1 , Pb-2). The Pb sites, located at the interface of two pentamers, were found for both MAD sets by SOLVE (Terwilliger, Acta Crystallogr. 55, 849-861 , 1999) and heavy atom parameters were optimized with SHARP (La Fortelle et al., Methods Enzymol. 276, 472-494, 1997). NCS operators were found and refined with NCS6D and IMP (Kleywegt and Jones, SERC Daresbury Laboratory, Warrington, pp. 59-66, 1994). DM-multi (Cowtan, Joint CCP4 and ESF-EACBM Newsletter on Protein Crystallography, 31 , 34-38, 1994) multi-crystal averaging used amplitudes of monoclinic, orthorhombic and native (tetragonal) data sets and experimental phases of the orthorhombic and monoclinic MAD experiments. The model was built in O (Jones et al., Acta Crystallogr. A47, 110-119, 1991) and refined with the program CNS (Brϋnger et al., Acta Crystallogr. D54, 905-921 , 1998), against the tetragonal data to 2.7 A resolution. Refinement included partial 5-fold NCS restraints, an overall anisotropic B factor and bulk solvent correction. The unusual double cysteine Cys187-Cys188 formed a clear disulfide bridge. Because of the limited resolution it was refined with standard parameters. The final model contains 1025 residues of AChBP pentamer, 5 HEPES molecules, 10 Ca²⁺ ions and 15 water molecules. The entire AChBP pentamer is well ordered, except for the N-terminal 7 residues (part of the signal sequence) and the last five C-terminal residues. In addition, the HEPES, the loop region 155-160 and the sugar residues attached to residue Asn66 are not well resolved in the electron density. R.m.s deviations from ideal geometry for bond distances and angles are 0.01 A and 1.6°, respectively. The sequence alignment was calculated by CLUSTALX (Thompson et al., Nucleic. Acids. Res. 25, 4876-4882, 1997) and the corresponding figure with Espript (Gouet et al., Bioinformatics. 15, 305-308, 1999). Figures 2-5 were done using programs MOLSCRIPT (Krauiis, P.J., J. Appl. Cryst. 24, 946-950, 1991), BOBSCRIPT (Esnouf, Acta Crystallogr. D55, 938- 940, 1999) and RASTER3D (Merritt and Bacon, Methods Enzymol. 277, 505-524, 1997). Refinement took place with partial five-fold NCS restraints, resulting in an R- factor of 26.4% (R_free = 30%).

The AChBP pentamer:

The AChBP homopentamer, when viewed along the five-fold axis, resembles a windmill toy, with petal-like monomers (Fig. 6a). When viewed perpendicular to the five-fold axis it has a disc-like appearance (Fig. 6b). The overall proportions of the pentamer are -80x80x62 A, and the diameter of the central hole is -18 A. These dimensions are in good agreement with the Torpedo nAChR N-terminal domain EM data (Miyazawa et al., J. Mol. Biol. 288, 765-786, 1999). The only subunit contacts in the AChBP pentamer are dimer interfaces, of which each monomer has two, one called the plus side and one called the minus side. We refer to the A (plus)-B (minus) interface, as example for the five equivalent interfaces AB, BC, CD, DE and EA (Fig 6).

The AChBP monomer:

Each AChBP monomer is a single domain protein, asymmetric in shape, with a size of -50x21x27 A (Fig. 12a). It consists of an N-terminal β-helix, two short 3₁₀ helices and a core of 10 β-strands forming a β-sandwich. The order of β-strands conforms to a modified immunoglobulin (Ig) topology (Fig. 12b) with an extra β-hairpin (f'-f") and an extra strand (b') (Bork et al., J. Mol. Biol. 242, 309-320, 1994). These additional strands introduce two so-called "Greek key" folding motifs. The lg-based structure prediction (Le Novere et al., 1999; Corringer et al., Biophys. J. 76, 2329-2345, 1999) agrees well with the AChBP structure, although location of the binding site was missed due to the presence of extra β-strands (Fig. 12b). Compared to the classical Ig-fold, the AChBP β-strands are considerably twisted, with the β-sheets rotated against each other, resulting in two separate hydrophobic cores. Thus the three- dimensional fold does not resemble other Ig-like proteins and comparison to the protein database (Holm and Sander, Nucleic. Acids. Res. 25, 231-234, 1997) did not result in a significant match to any known structure. Positioning of functional regions:

Couple of regions that are important to receptor function can be localized in the AChBP structure. In muscle type nAChRs the main immunogenic region (MIR), comprising residues αι67-α₁76, acts as an epitope in the autoimmune disease myasthenia gravis (Tzartos et al., Mol. Neurobiol. 5, 1 -29, 1991 ). Although the MIR- related region in AChBP (residues 65-72) shows no sequence homology to the α subunit, its location in loop L3 at the top of the pentamer in a highly accessible position agrees well with the expected accessibility for this region. It also fits with EM studies that located the MIR at the distal end of the receptor relative to the membrane (Beroukhim and Unwin, Neuron 15, 323-331 , 1995). On each AChBP monomer, a large cavity that is accessible from the central pore of the pentameric ring can be seen. The cavity is framed at the entrance by β-strands (β3, β4, β5 and β5') (Fig 12a) and is uncharged, mainly hydrophobic, in character. This region probably corresponds to the tunnel framed by twisted β-strands that was observed in the α-psubunit of Torpedo receptor at 4.6 A resolution (Miyazawa et al.,

J. Mol. Biol. 288, 765-786, 1999). However, this cavity is not in contact with another large pocket observed at each interface between subunits. These latter pockets are lined by residues shown to be involved in ligand binding in nAChR (Arias, Neurochem. Int. 36, 595-645, 2000; Corringer et al., Annu. Rev. Pharmacol. Toxicol. 40, 431-458, 2000). They are buried from the solvent, and located close to the outside of the pentameric ring. When viewed perpendicular to the five-fold axis they are roughly equatorially positioned, -30 A away from the C-termini (Fig. 6b), conforming to the expected location of the Torpedo receptor ligand-binding site, as determined by labeling (Fernando Valenzuela et al., Biophys. J. 66, 674-682, 1994) and EM studies (Unwin, J. Mol. Biol. 229, 1101-1124, 1993).

The ligand-binding site: Each ligand-binding site is found in a cleft formed by a series of loops from the principal face of one subunit and a series of β-strands from the complementary face of an adjacent subunit. It is a large cavity buried by a series of loops from the principal side and by a β-strands from the complementary side (Fig. 13). The principal side on the plus side of the AB interface consists of residues coming from 'loop A' (TyrA89), 'loop B' (TrpA143, A145) and 'loop C (TyrA185, the double cysteine A187-A188, and TyrA192) (Fig 13c). The complementary part of this binding site is contributed by monomer B and made of 'loop D' (TrpB53, GlnB55), 'loop E'

(ArgB 04, ValB106, LeuB112 and MetB114) and 'loop F (TyrB164) (Fig 13d). In this pocket four of the aromatic residues form the bottom half of the cavity (TyrA89,

TyrA185, TyrB164 and TrpB53). The pocket walls are formed by the TyrA192, TrpA143, main chain of A145 Met B114, the side-chain of GlnB55 and the double cysteine (CysA187-CysA188). The hydrophobic parts of ArgB104, ValB106 and

LeuB112 form the top of the pocket (Fig 13a).

All residues in the pocket had been successfully identified by photoaffinity labeling and mutagenesis studies (Arias, Neurochem. Int. 36, 595-645, 2000; Corringer et al., Annu. Rev. Pharmacol. Toxicol. 40, 2000). Although the side chain of HisA145 is pointing away from the cavity, its main chain is involved. One residue identified by labeling studies, TrpA82 (αιTrp86) (Galzi et al., J. Biol. Chem. 265, 10430-10437, 1990; Dennis et al., Biochemistry 27, 2346-2357, 1988) is involved in hydrophobic core formation and located far from the pocket, thus not participating in ligand binding. Otherwise, the AChBP ligand-binding site confirms the available biochemical and mutational data on nAChR completely.

The structure, however, shows for the first time how these residues are positioned with respect to each other and therefore provide a valuable tool for drug design as described in the above description of the present invention.

All observed residues are conserved between known nicotinic ligand-binding subunits except the 'loop F TyrB164 residue. The 'loop F' region has an unusual conformation, but since it is relatively weakly resolved, its precise analysis is difficult. The 'loop F' region is stabilized in the structure by a calcium binding site formed by AspB161 , AspB175 and the main chain of B176. This Ca²⁺ ion is structurally important for TyrB164 orientation and could therefore be important for proper ligand binding. The present findings are supported by labeling studies on muscle/Torpeαto subunits showing that residues homologous to AspB161 , γAsp174/δAsp180 play a role in ligand binding (Czajkowski et al., Proc. Natl. Acad. Sci. U.S.A. 90, 6285-6289, 1993; Czajkowski and Karlin, J. Biol. Chem. 270, 3160-3164, 1995; Martin et al., J. Biol. Chem. 271 , 13497-13503, 1996). Additionally, calcium binding sites that enhance the response to agonist binding have been identified in the homologous region (residue range 161-172) of neuronal α₇ receptor (Galzi et al., EMBO J. 15, 5824-5832, 1996). The 'loop F' region has low sequence conservation in the nicotinic family (Fig. 11) and in other superfamily members it may well have a different conformation, even to the extent of forming a β-strand that connects the two sheets into a β-barrel. Such changes could well lead to variations in affinity, e.g. by changing the size of the ligand-binding site or its access route.

The most likely access routes to the ligand binding sites are from above or below the double-cysteine-containing oop C (Fig. 13a). This region buries the pocket from the solvent and therefore prevents access from the outside. Access from the central pore has been suggested in the literature (Miyazawa, J. Mol. Biol. 288, 765-786, 1999), but this would require major structural rearrangements at the interface, which makes it less likely.

Ligand binding:

Surprisingly, features of bulky electron density were found that stacked onto Trp143 in each ligand-binding site in the experimental cross-crystal averaged electron density (Fig 13b). Upon consideration we have assigned this to a HEPES (N-2- Hydroxyethylpiperazine-N'-2-ethanesulfonic acid) buffer molecule, that contains a positively charged quaternary ammonium group and therefore has some similarity to known nicotinic receptor ligands. Its EC50 is 100 mM, indicating that its binding under crystallization conditions (100-150 mM) is possible. Although HEPES molecule does not make any specific contacts with the protein, it stacks with its quaternary ammonium onto Trp143, making cation-π interactions as expected for nicotinic agonists (Dougherty, Science 271 , 163-168, 1996) (Fig. 13b). However, due to limited resolution of the present data and probable low occupancy, the precise orientation of the HEPES molecule should be taken with some degree of reservation.

It has been suggested (Changeux and Edelstein, Neuron 21 , 959-980, 1998) that the ligand-binding site of nAChRs could be similar to that of acetylcholinesterase (AChE). Although the size of the binding site is roughly similar in AChBP and AChE, the observed arrangement of aromatic residues is quite different. However, the stacking of the quaternary ammonium of HEPES, as far as it has been refined in the current AChBP structure, is similar to that of the quaternary ammonium of the decamezonium in AChE on the Trp84 residue (Harel et al., Proc. Natl. Acad. Sci. U.S.A. 90, 9031 -9035, 1993).

Subunit arrangement: From the location of the ligand-binding site conclusions can be drawn about the relative arrangement of subunits in the Torpedo and muscle receptors. It has been suggested that the αiγ and a δ interfaces occur in a clockwise α-iγαiδβi arrangement when looking towards the membrane (Machold et al., Eur. J. Biochem. 234, 427-430, 1995). Such a clockwise arrangement disagrees with the structure determined in accordance with the present invention, because the relative arrangement of the principal binding site and its complementary partner is anticlockwise when looking towards the 'bottom' (membrane) side of the pentamer (Fig. 6).

Pentamer interface:

The subunit interface consists on the plus side entirely of loop regions (L1 , L2, L4, L5, L7, L8 and L10), whereas the minus side mostly presents secondary structure elements to the interface (α1 , β1 , β2, β3, β5, βδ and L9) (Fig. 14). Several residues are important for both ligand-binding and pentamer formation. The interface buries a considerably surface area (2700 A²), with a mainly uncharged character including only a single bifurcated salt bridge (GluA149-ArgB3 and ArgB104). Most intriguing about the interface residues is the lack of conservation of these particular residues in the entire superfamily, not only with AChBP, but also amongst each other (Fig. 11). These changes involve major changes in character, including changes from hydrophobic to charged. Even when a residue is conserved in any particular subunit, its expected counterpart is missing (either in the same subunit, as in the α₇ homopentamers, or in contacts such as muscle α-j δ or α-jγ or neuronal α4β2) with the sole exception of the ligand-binding site. The high level of structural conservation however, determines involvement of the same topological regions in these contacts in all family members (Fig 14b). This indicates that shape complementarity must play a major role in determining the conservation of the pentamer structure. It also indicates that different combinations of subunits will have different interfaces, creating variations in the precise allosteric contacts and movements in the various subclasses of these ion channels.

Ligand-gated ion channels: The lack of conservation of the interface residues seems a general feature in the superfamily of LGICs, as the residues that form the interface are among the least conserved regions of the domains (Fig. 11 ). Apparently pentamer formation does not impose very stringent evolutionary requirements in this case. However, there is clear sequence conservation within the superfamily (Fig. 1 1 ) and it is interesting to analyze this in the light of the structure. In the AChBP monomer structure the conserved hydrophobic residues can be grouped into three clusters (Fig. 15). In AChBP, as in other proteins with lg-like fold, the packing of the β-sheets is promoted mainly by hydrophobic and to a lesser extent by electrostatic interactions. The first cluster is involved in packing of the N-terminal helix α1 against the main framework of the monomer and it involves residues 6, 10, 63, 65, 71 , 81 , 105 and 11 1 . The second cluster, comprising residues 20, 27, 29, 31 , 58, 82, 84, 86, 140, 150, 152 and 195, is situated in the upper half of the β-core region. The third cluster, including residues 33, 35, 38, 41 , 48, 52, 125, 138, 171 , 173, 199 and 201 , is located at the lower end of the structure (Fig 15). The only non- hydrophobic residues that are highly conserved in the superfamily are Asp60, Asp85, Asn90 and Gly109. Asp60 and Gly109 are involved stabilizing the turns of a Greek key motif connecting strands β3, β5, β6 and β2, where Asp60 stabilizes the N- terminus of a small 3₁₀ helix and Gly109 enables tight turn formation. Conserved residues Asp85 and Asn90 are involved in packing of the β-sheets. Asp85 forms hydrogen bonds to the highly conserved Ser142 and Thr144 and residue Asn90 brings together the main-chain oxygens of Ser122 and Arg137, enabling disulfide bond formation of the nearby absolutely conserved disulfide bond (123-136). This disulphide bond is topologically equivalent to so-called 'tyrosine cornerstone' (Hemmingsen et al., Protein Sci. 3, 1927-1937, 1994), which links the two β-sheets together in lg-like proteins. This explains why in the Torpedo receptor the Cys128- Cys142 bond is important for both preservation of subunit conformational stability (Mishina et al., Nature 313, 364-369, 1985) and complete nAChR assembly (Green & Wanamaker, J. Neurosci. 18, 5555-5564, 1998). Since the observed overall structural conservation is high, it is clear that all LGIC N-terminal domains will have the same three-dimensional structure.

In contrast to the above residues, the Cys-loop is a highly conserved hydrophobic region in the LGIC family but presents a totally different character in AChBP (Fig. 11 ).

In AChBP, this loop is hydrophilic and is found at the bottom (membrane) side of the protein, at the dimer interface. This location and its hydrophobicity in the LGIC family implies that this loop could interact with the membrane or with the transmembrane region of the receptors, functions that are absent in AChBP.

Since all ligand gated ion channels have intrinsically the same function, opening of a membrane pore, it is likely that the conserved regions of the protein determine this function. That also indicates that it is unlikely that the interface of the pentamer has a major role in opening the channel. It is possible that the conserved Cys-loop is directly involved in transmitting this kind of information to the membrane part of the LGICs. Another option is that large structural changes in the β-sheet regions play a role in opening the channel. Indeed, the movement observed at 9 A for Torpedo nAChR upon agonist binding (Unwin, Nature 373, 37-43, 1995), fits well with such a suggestion. In accordance with the present invention a twisted β-sandwich would be observed, with two distinct hydrophobic cores and it is entirely possible that these cores move with respect to each other upon ligand binding. The effect of such movements will then be modulated by the varying subunit interfaces in the different subtypes of the receptor, allowing intricate specificity in the neuronal signal transmission.

EXAMPLE 9: Ligand-binding crystallization studies

AChBP was cocrystallized in complex with α-bungarotoxin (αBTX, Sigma). Prior to the crystallization experiments the stability of the complex has been investigated. Using gel-filtration chromatography (Superdex 200 HR 10/30, Pharmacia, column volume 24 ml) it has been found that it is possible to purify stable complex between AChBP and αBTX. The gel-filtration run was performed using 20 mM Tris (pH 8.0), 150 mM NaCl and 0.02% NaN₃. The stability of the complex was also confirmed with native PAGE. The crystallization experiments were done based on the same set of conditions found to work for AChBP alone; see Example 6. A small screen was set up with different precipitant concentrations and various AChBP:α BTX concentrations. Tiny crystals appeared in the conditions containing 10-12% PEG 4000, 100 mM HEPES (pH 7.0), 20-80 mM CaCI₂ and 0.02% NaN₃. The best looking crystals grew under above mentioned conditions when AChBP: (BTX were mixed in 1 :10 molar ratio. In order to check if complex indeed crystallized, crystals were thoroughly washed, dissolved in denaturing buffer and checked on SDS-PAGE that clearly showed that they contained both proteins.

In addition, a number of small ligands were bound to AChBP in soaking experiments. These include: B-bippinatin (a synthetic analog of lophotoxin), acetylcholine (ACh, Sigma), d-tubocurarine chloride (Sigma), carbamylcholine chloride (CCh, Sigma), galanthamine hydrobromide (Sigma), epibatidine (Sigma) and nicotine (Sigma). The soaking solutions were made of stabilizing solutions (see Example 6) and together with dissolved ligands (ligands were normally dissolved in 20 mM HEPES [pH 7.0]). The ligand concentrations used were dependent on its binding constants, as determined by ligand-binding studies. The soaking times were different depending on the ligand used. After the soaking step the crystals were flash-cooled in liquid nitrogen. EXAMPLE 10: Generating human alpha7 nAChR /AChBP chimeras

The chimeric proteins of nAChR subunits and AChBP can be used as tools in the development of novel, nAChR subtype specific ligands. As a first step in developing these tools chimeric proteins have been designed and constructed in which part(s) of the human alpha7 nAChR were grafted into AChBP. Previous studies on the molecular determinants of ligand-binding by the alpha7 nAChR have identified three amino acid domains that compose the primary part of the ligand-binding site, further referred to as "loops A, B, and C". Within each of the three loops amino acid residues are present that are thought to directly interact with the ligand. Based on sequence conservation of the nAChR and AChBP the three possible ligand-binding loops of AChBP have been pin-pointed in accordance with the present invention as follows: loop A, Trp-101 -> Tyr-108; loop B, Trp-162 -> His-164; loop C, Tyr-204 -> Tyr-211. The chimeric proteins that were constructed replace either one (A, B or C) or multiple (A&B, A&C, B&C and A&B&C) of the ligand-binding loops of AChBP with the corresponding human alpha7 nAChR sequence.

The loop-A domain of AChBP was replaced by the corresponding domain of the human alpha7 nAChR using a two-step polymerase chain reaction (PCR). In the first step two separate PCR amplifications (35 cycles: 94 °C;30 sec, 58 ^gC; 30 sec and 72 ^SC; 60 sec.) yielded two halves of the chimera construct. AChBP cDNA (wild type) was used as template, and outer primers located either just before the start codon (gcgctcgagaaaagagaggctgaagctttggaccgggcagacatctt; SEQ ID No. 17) or just before the stop codon (cgcgaattcaagaatttcggagcgtccctt; SEQ ID No. 18) were each used in combination with two internal primers gtggaaaccagacattctcctctacaacgccatctcgaaacc (SEQ ID No. 19) and gaggagaatgtctggtttccacaaagagcttattggcac (SEQ ID No. 20), respectively. The internal primers contained a 5'-tag-sequence that encoded for the introduced alpha7 nAChR domain. As such the two generated chimeric PCR products share a common tag containing a part of the alpha7 nAChR subunit. In the second step, the two PCR products from the first round were pooled and, in the absence of primers, went through 5 rounds of PCR amplification (94 ^aC; 30 sec, 54 ^SC; 3 mm. and 72 ²C; 90 se ). This allowed the two halves of the chimera to anneal to each other at the common alpha7 nAChR tag. The subsequent addition of the two outer primers and another 35 cycles of 25 PCR amplification (94 ^SC; 30 sec, 58 ⁹C; 30 sec. and 72 ^aC; 90 sec.) yielded the final chimera construct. Al! PCR amplifications were hot-started and performed using PFU DNA-polymerase (Invitrogen). The loop-A AChBP/alpha7 chimera was cloned, using Xhol/EcoRI restriction sites in the outer primers, into the His-tag containing yeast expression vector pPIC9 (Invitrogen). Validation of the construct was achieved by DNA sequencing. Expression of the chimera construct was achieved according to the

Pichia pastoris protein expression protocol of Invitrogen.

As described in the examples and the description, the present invention provides water-soluble ligand-binding proteins derived from molluscs and analogs of ligand- gated ion channels, crystals thereof and their use for screening ligands of ligand- gated ion channels. In particular, ligand-binding proteins have been identified that are capable of forming multimers and are amenable to crystallization. The crystal! structure of one these proteins, an acetylcholine binding protein (AChBP) is provided, which can be used to generate 3D models of the extracellular ligand-binding domain of ligand-gated ion channels and thus for screening of drugs that act on these ion channels. Furthermore, chimeric proteins are provided that are capable of binding a ligand of a ligand-gated receptor, and comprising at least the amino acids of the AChBP determining solubility of the AChBP, in the same positions as in the AChBP, and furthermore comprising amino acids determining binding to said ligand. It will be clear that the invention may be practiced otherwise than as particularly described in the foregoing description and examples. Numerous modifications and variations of the present invention are possible in light of the above teachings and, therefore, are within the scope of the appended claims.

The entire disclosure of each document cited (including patents, patent applications, journal articles, abstracts, laboratory manuals, books, or other disclosures) in the Background of the Invention, Description, and Examples is hereby incorporated herein by reference. Moreover, the sequence listing is herein incorporated by reference.

- IΔ

Table 1

REMARK Written by O version 7.0 .1

CRYST1 141. 660 141.66C ) 120.870 90.00 90.00 90.00

ORIGX1 1.000000 0. 000000 0.000000 0.00000

ORIGX2 0.000000 1. ,000000 0.000000 0.00000

ORIGX3 0.000000 0. ,000000 1.000000 0.00000

SCALΞ1 0.007059 0. ,000000 0.000000 0.00000

SCALE2 0.000000 0. ,007059 0.000000 0.00000

SCALE3 0.000000 0. ,000000 0.008273 0.00000

ATOM 1 CB PHE A 1 65.468 25. 127 1.161 1. 00 73. 24 6

ATOM 2 CG PHE A 1 64.224 24. ,803 0.370 1. 00 76. 49 6

ATOM 3 GDI PHE A 1 63.433 25. 819 -0.178 1. 00 77. 52 6

ATOM 4 CD2 PHE A 1 63.798 23. ,471 0.244 1. 00 78. 15 6

ATOM 5 CE1 PHE A 1 62.224 25. ,522 -0.840 1. 00 79. 11 6

ATOM 6 CE2 PHE A 1 62.590 23. ,148 -0.412 1. 00 79. 82 6

ATOM 7 CZ PHE A 1 61.797 24. ,179 -0.958 1. 00 79. 89 6

ATOM 8 C PHE A 1 66.638 27. ,146 1.923 1. 00 69. 89 6

ATOM 9 O PHE A 1 67.034 26. ,519 2.903 1. 00 70. 26 8

ATOM 10 N PHE A 1 67.407 25. .990 -0.118 1. ,00 71. ,31 7

ATOM 11 CA PHE A 1 66.214 26. .375 0.689 1. ,00 70. ,93 6

ATOM 12 N ASP A 2 66.562 28. .478 1.909 1. ,00 68. ,78 7

ATOM 13 CA ASP A 2 66.958 29. .233 3.105 1. ,00 68. ,57 6

ATOM 14 CB ASP A 2 67.577 30. .615 2.739 1. ,00 69 . ,98 6

ATOM 15 CG ASP A 2 66.639 31. .523 1.914 1. 00 73. ,55 6

ATOM 16 OD1 ASP A 2 67.059 32, .068 0.844 1. ,00 73. ,75 8

ATOM 17 OD2 ASP A 2 65.485 31, .714 2.349 1. ,00 75. ,27 8

ATOM 18 C ASP A 2 65.794 29, .374 4.102 1. .00 67. .66 6

ATOM 19 O ASP A 2 64.622 29. .273 3.719 1. ,00 68. ,25 8

ATOM 20 N ARG A 3 66.126 29 .560 5.386 1. .00 65. .60 7

ATOM 21 CA ARG A 3 65.131 29, .703 6.453 1. .00 60. .77 6

ATOM 22 CB ARG A 3 . 65.765 30, .222 7.737 1. .00 60. ,30 6

ATOM 23 CG ARG A 3 66.393 29, .174 8.604 1. ,00 59. ,51 6

ATOM 24 CD ARG A 3 66.375 29, .629 10.048 1. .00 61. .41 6

ATOM 25 NE ARG A 3 66.440 28 .471 10.927 1, .00 61, .03 7

ATOM 26 CZ ARG A 3 67.550 27 .787 11.159 1, .00 62, .03 6

ATOM 27 NH1 ARG A 3 68.692 28, .169 10.586 1. . 00 60. .01 7

ATOM 28 NH2 ARG A 3 67.509 26 .694 11.918 1, .00 62. .76 7

ATOM 29 C ARG A 3 64.034 30 .659 6.055 1. .00 59, .92 6

ATOM 30 O ARG A 3 62.883 30 .487 6.454 1 .00 59 .64 8

ATOM 31 N ALA A 4 64.395 31 .685 5.291 1, .00 57 .25 7

ATOM 32 CA ALA A 4 63.404 32 .641 4.836 1, .00 55, .16 6

ATOM 33 CB ALA A 4 64.065 33 .782 4.088 1, .00 53 .78 6

ATOM 34 C ALA A 4 62.421 31 .917 3.927 1, .00 54, .69 6

ATOM 35 0 ALA A 4 61.213 32 .062 4.074 1 .00 55 .60 8

ATOM 36 N ASP A 5 62.942 31 .127 2.995 1, .00 54, .79 7

ATOM 37 CA ASP A 5 62.097 30 .392 2.060 1 .00 55 .84 6

ATOM 38 CB ASP A 5 62.937 29 .580 1.058 1 .00 56 .83 6

ATOM 39 CG ASP A 5 63.918 30 .437 0.278 1 .00 59 .97 6

ATOM 40 ODl ASP A 5 63.519 31 .519 -0.213 1 .00 61 .60 8

ATOM 41 OD2 ASP A 5 65.095 30 .025 0.148 1. .00 62 .19 8

ATOM 42 C ASP A 5 61.176 29 .443 2.815 1 .00 55 .90 6

ATOM 43 O ASP A 5 60.011 29 .268 2.445 1 .00 53 .57 8

ATOM 44 N ILE A 6 61.695 28 .832 3.877 1 .00 55 .26 7

ATOM 45 CA ILE A 6 60.890 27 .889 4.650 1 .00 55 .12 6

ATOM 46 CB ILE A 6 61.743 27 .107 5.657 1 .00 55 .82 6

ATOM 47 CG2 ILE A 6 60.878 26 .056 6.354 1 .00 53 .18 6

ATOM 48 CGI ILE A 6 62.924 26 .455 4.933 1 .00 56 .24 6

ATOM 49 CD1 ILE A 6 63.802 25 .568 5.816 1 .00 59 .65 6

ATOM 50 C ILE A 6 59.742 28 .561 5.396 1 .00 54 .71 6 ATOM 51 O ILE A 6 58.589 28.159 5.256 1.00 55.75

ATOM 52 N LEU A 7 60.058 29.583 6.182 1.00 52.58- 7

ATOM 53 CA LEU A 7 59.041 30.299 6.929 1.00 51.88 6

ATOM 54 CB LEU A 7 59.697 31.387 7.784 1.00 51.65 6

ATOM 55 CG LEU A 7 60.589 30.828 8.895 1.00 51.59 6

ATOM 56 CD1 LEU A 7 61.484 31.902 9.480 1.00 51.45 6

ATOM 57 CD2 LEU A 7 59.700 30.225 9.953 1.00 51.32

ATOM 58 C LEU A 7 58.048 30.915 5.961 1.00 51.46

ATOM 59 O LEU A 7 56.846 30.921 6.204 1.00 51.87

ATOM 60 N TYR A 8 58.561 31.417 4.848 1.00 51.83

ATOM 61 CA TYR A 8 57.727 32.041 3.832 1.00 53.61

ATOM 62 CB TYR A 8 58.601 32.520 2.672 1.00 55.43

ATOM 63 CG TYR A 8 57.806 33.119 1.543 1.00 57.65

ATOM 64 CD1 TYR A 8 57.217 34.379 1.668 1.00 58.24

ATOM 65 CΞ1 TYR A 8 56.439 34.914 0.644 1.00 58.94

ATOM 66 CD2 TYR A 8 57.601 32.407 0.366 1.00 58.93

ATOM ■67 CE2 TYR A 8 56.825 32.930 -0.665 1.00 60.13

ATOM 68 CZ TYR A 8 56.244 34.183 -0.518 1.00 60.03

ATOM 69 OH TYR A 8 55.453 34.699 -1.527 1.00 63.97

ATOM 70 C TYR A 8 56.636 31.114 3.296 1.00 52.67

ATOM 71 O TYR A 8 55.483 31.511 3.143 1.00 52.13

ATOM 72 N ASN A 9 57.009 29.880 2.997 1.00 53.39

ATOM 73 CA ASN A 9 56.051 28.918 2.488 1.00 53.87

ATOM 74 CB ASN A 9 56.750 27.613 2.096 1.00 58.21

ATOM 75 CG ASN A 9 57.646 27.772 0.860 1.00 62.45

ATOM 76 OD1 ASN A 9 57.647 28.824 0.209 1.00 64.72

ATOM 77 ND2 ASN A 9 58.405 26.724 0.530 1.00 62.99

ATOM 78 C ASN A 9 54.987 28.638 3.526 1.00 53.31

ATOM 79 O ASN A 9 53.794 28.725 3.239 1.00 52.02

ATOM 80 N ILE A 10 55.420 28.300 4.736 1.00 53.77

ATOM 81 CA ILE A 10 54.489 28.018 5.829 1.00 55.18

ATOM 82 CB ILE A 10 55.229 27.788 7.150 1.00 53.51

ATOM 83 CG2 ILE A 10 54.220 27.639 8.272 1.00 53.99

ATOM 84 CGI ILE A 10 56.109 26.541 7.044 1.00 50.48

ATOM 85 CD1 ILE A 10 57.043 26.346 8.202 1.00 47.68

ATOM 86 C ILE A 10 53.523 29.183 6.032 1.00 57.42

ATOM 87 O ILE A 10 52.319 28.997 6.221 1.00 57.74^'

ATOM 88 N ARG A 11 54.070 30.390 5.997 1.00 58.29

ATOM 89 CA ARG A 11 53.283 31.600 6.156 1.00 60.48

ATOM 90 CB ARG A 11 54.199 32.810 6.042 1.00 64.72

ATOM 91 CG ARG A 11 53.513 34.134 6.270 1.00 70.99

ATOM 92 CD ARG A 11 53.241 34.337 7.757 1.00 79.75 6

ATOM 93 NE ARG A 11 53.059 35.751 8.105 1.00 86.33 7

ATOM 94 CZ ARG A 11 53.848 36.733 7.665 1.00 89.85 6

ATOM 95 NHl ARG A 11 54.871 36.451 6.845 1.00 92.68 7

ATOM 96 NH2 ARG A 11 53.636 37.992 8.056 1.00 90.02 7

ATOM 97 C ARG A 11 52.204 31.701 5.082 1.00 59.54 6

ATOM 98 O ARG A 11 51.038 31.954 5.363 1.00 59.64 8

ATOM 99 N GLN A 12 52.614 31.489 3.841 1.00 59.22 7

ATOM 100 CA GLN A 12 51.718 31.595 2.705 1.00 58.15 6

ATOM 101 CB GLN A 12 52.542 ^'31.776 1.441 1.00 59.05 6

ATOM 102 CG GLN A 12 52.118 32.961 0.629 1.00 60.64 6

ATOM 103 CD GLN A 12 .52.674 34.226 1.192 1.00 61.53

ATOM 104 OE1 GLN A 12 53.879 34.345 1.360 1.00 65.50

ATOM 105 NE2 GLN A 12 51.811- 35.182 1.489 1.00 62.18

ATOM 106 C GLN A 12 50.732 30.460 2.472 1.00 57.30

ATOM 107 O GLN A 12 49.714 30.651 1.814 1.00 57.03

ATOM 108 N THR A 13 51.029 29.280 2.987 1.00 56.84

ATOM 109 CA THR A 13 50.142 28.147 2.773 1.00 57.26

ATOM 110 CB THR A 13 50.922 26.964 2.186 1.00 57.29

ATOM 111 OG1 THR A 13 52.000 26.616 3.071 1.00 55.40 ATOM 112 CG2 THR A 13 51.477 27.326 0.813 1.00 58.15 6

ATOM 113 C THR A 13 49. 411 27. 650 4. 013 1. 00 58. 45 6

ATOM 114 O THR A 13 48. 423 26. ,932 3. 905 1. 00 58. 36 8

ATOM 115 N SER A 14 49. ,892 28. ,034 5. 187 1. 00 60. 01 7

ATOM 116 CA SER A 14 49. 290 27. 584 6. 424 1. 00 60. 03 6

ATOM 117 CB SER A 14 50. 198 27. ,930 7; 601 1. 00 61. 46 6

ATOM 118 OG SER A 14 49. 813 27. ,207 8. 758 1. 00 65. 18 8

ATOM 119 C SER A 14 47. ,899 28. ,147 6. ,664 1. ,00 59. ,50 6

ATOM 120 O SER A 14 47. ,560 29. .240 6. ,189 1. ,00 58. ,72 8

ATOM 121 N ARG A 15 47. ,102 27. ,377 7. 407 1. 00 58. 04 7

ATOM 122 CA ARG A 15 45. 740 27. ,753 7. 755 1. 00 55. 62 6

ATOM 123 CB ARG A 15 44. ,744 26. ,996 6. ,877 1. ,00 56. ,74 6

ATOM 124 CG ARG A 15 44. .925 27, .253 5. .385 1. .00 59. .62 6

ATOM 125 CD ARG A 15 43. 688 26. ,851 4. 614 1. 00 61. ,99 6

ATOM 126 NE ARG A 15 42. ,519 27, .540 5. .151 1. ,00 64. .02 7

ATOM 127 CZ ARG A 15 41. .261 27, .216 4. .870 1. ,00 65. ,48 6

ATOM 128 NH1 ARG A 15 41. .007 26, .201 4. .050 1. ,00 67. ,33 7

ATOM 129 NH2 ARG A 15 40. .256 27, .908 5. .408 1. .00 64. .23 7

ATOM 130 C ARG A 15 45. .516 27. .420 9. ,219 1. ,00 52. .12 6

ATOM 131 O ARG A 15 45. .135 26, .310 9. .562 1. .00 53. .25 8

ATOM 132 N PRO A 16 45, .751 28, .392 10. .104 1. .00 50. .04 7

ATOM 133 CD PRO A 16 46 .198 29 .750 9 .773 1, .00 48 .52 6

ATOM 134 CA PRO A 16 45. .597 28, .249 11. ,551 1. .00 49. ,56_. 6

ATOM 135 CB PRO A 16 45, .959 29 .634 12, .073 1. .00 49. ,66 6

ATOM 136 CG PRO A 16 46, .870 30 .165 11, .041 1, .00 49, .57 6

ATOM 137 C PRO A 16 44, .215 27, .816 12. .016 1. .00 50, .11 6

ATOM 138 O PRO A 16 44, .060 27, .322 13, .131 1. .00 51, .27 8

ATOM 139 N ASP A 17 43, .208 28 .013 11. .176 1, .00 50, .70 7

ATOM 140 CA ASP A 17 41, .856 27 .640 11, .548 1, .00 50, .64 6

ATOM 141 CB ASP A 17 40, .850 28 .609 10, .931 1, .00 54, .16 6

ATOM 142 CG ASP A 17 40 .873 29 .974 11 .592 1. .00 59, .76 6

ATOM 143 OD1 ASP A 17 41, .245 30, .060 12, .791 1, .00 60. .67 8

ATOM 144 OD2 ASP A 17 40, .500 30 .965 10, .920 1, .00 62, .99 8

ATOM 145 C ASP A 17 41 .482 26 .218 11 .157 1, .00 50 .71 6

ATOM 146 O ASP A 17 40 .353 25 .783 11, .390 1, .00 48, .36 8

ATOM 147 N VAL A 18 42 .429 25 .484 10, .583 1, .00 51, .85 7

ATOM 148 CA VAL A 18 42 .143 24 .128 10 .148 1, .00 52 .53 6

ATOM 149 CB VAL A 18 42 .262 24 .011 8 .622 1, .00 53, .05 6

ATOM 150 CGI VAL A 18 41 .834 22 .618 8 .169 1, .00 51, .38 6

ATOM 151 CG2 VAL A 18 41 .396 25 .077 7 .963 1, .00 51, .76 6

ATOM 152 C VAL A 18 42 .993 23 .050 10, .779 1 .00 52 .56 6

ATOM 153 O VAL A 18 44 .199 23 .006 10 .588 1 .00 52 .64 8

ATOM 154 N ILE A 19 42 .327 22 .172 11 .519 1 .00 53 .41 7

ATOM 155 CA ILE A 19 42 .954 21 .042 12. .202 1, .00 52, .70 6

ATOM 156 CB ILE A 19 41 .871 20 .319 13 .072 1 .00 52, .71 6

ATOM 157 CG2 ILE A 19 40 .819 19 .671 12 .190 1 .00 52 .40 6

ATOM 158 CGI ILE A 19 42 .504 19 .290 13 .992 1 .00 53 .50 6

ATOM 159 GDI ILE A 19 41 .546 18 .811 15 .056 1 .00 50 .39 6

ATOM 160 C ILE A 19 43 .596 20 .097 11 .164 1 .00 52 .96 6

ATOM 161 O ILE A 19 42 .957 19 .687 10 .193 1 .00 51 .39 8

ATOM 162 N PRO A 20 44 .878 19 .757 11 .355 1 .00 53 .70 7

ATOM 163 CD PRO A 20 45 .711 20 .210 12 .472 1 .00 54 .14 6

ATOM 164 CA PRO A 20 45 .644 18 .876 10 .461 1 .00 56 .34 6

ATOM 165 CB PRO A 20 47 .078 18 .996 10 .981 1 .00 56 .60 6

ATOM 166 CG PRO A 20 47 .060 20 .235 11 .840 1 .00 58 .05 6

ATOM 167 C PRO A 20 45 .177 17 .432 10 .474 1 .00 58 .61 6

ATOM 168 O PRO A 20 45 .974 16 .523 10 .682 1 .00 59 .22 8

ATOM 169 N THR A 21 43 .886 17 .231 10 .246 1 .00 62 .30 7

ATOM 170 CA THR A 21 43 .283 15 .900 10 .236 1 .00 66 .91 6

ATOM 171 CB THR A 21 41 .765 16 .020 10 .495 1 .00 65 .83 6

ATOM 172 OG1 THR A 21 41 .516 15 .813 11 .883 1 .00 67 .19 8 ATOM 173 CG2 THR A 21 40.975 15.010 9.,687 1.,00 68.42 6

ATOM 174 C THR A 21 43. 522 15. ,060 8. ,967 1. 00 70. 65 6

ATOM 175 O THR A 21 43. 365 15. ,538 7. ,832 1. ,00 70. 53 8

ATOM 176 N GLN A 22 43. 899 13. ,802 9. ,179 1. 00 74. ,54 7

ATOM 177 CA GLN A 22 44. 152 12. 844 8. 096 1. 00 78. 38 6

ATOM 178 CB GLN A 22 45. 513 12. ,180 8. 296 1. 00 79. 92 6

ATOM 179 CG GLN A 22 46. 668 13. ,174 8. ,402 1. 00 83. 40 6

ATOM 180 CD GLN A 22 47. ,836 12. ,640 9. ,244 1. ,00 84. ,08 6

ATOM 181 OE1 GLN A 22 47. ,709 12. .451 10. .467 1. ,00 82. ,79 8

ATOM 182 NE2 GLN A 22 48. ,976 12. .397 8. .592 1. .00 83. ,48 7

ATOM 183 C GLN A 22 43. ,055 11. .779 8. .158 1. ,00 80. ,25 6

ATOM 184 0 GLN A 22 43. 050 10. ,929 9. ,058 1. ,00 80. 25 8

ATOM 185 N ARG A 23 42. 133 11. ,825 7. .199 1. 00 82. ,59 7

ATOM 186 CA ARG A 23 40. ,999 10. ,896 7. ,162 1. ,00 84. 29 6

ATOM 187 CB ARG A 23 41. ,478 9. .447 7. .095 1. .00 85. .05 6

ATOM 188 CG ARG A 23 41. .983 9. .032 5. .717 1. .00 87. .64 6

ATOM 189 CD ARG A 23 43. .517 8, .991 5. .617 1. .00 90. ,14 6

ATOM 190 NE ARG A 23 43. .958 8, .775 4, .231 1. .00 92. .92 7

ATOM 191 CZ ARG A 23 43. .557 7. .768 3. ,447 1. ,00 94. ,10 6

ATOM 192 NH1 ARG A 23 42. ,700 6. .854 3. .901 1. ,00 94. ,07 7

ATOM 193 NH2 ARG A 23 44. ,000 7. .687 2. .195 1. ,00 93. ,77 7

ATOM 194 C ARG A 23 40. .130 11. .099 8. .399 1. ,00 85. ,22 6

ATOM 195 O ARG A 23 39. ,979 12. .237 8. .881 1. .00 84. ,91 8

ATOM 196 N ASP A 24 39, .549 10, .011 8, .908 1. .00 86, .21 7

ATOM 197 CA ASP A 24 38, .705 10 .105 10, .105 1, .00 86, .07 6

ATOM 198 CB ASP A 24 37. ,689 8. .952 10. ,194 1. ,00 89. ,13 6

ATOM 199 CG ASP A 24 37. ,418 8, .289 8, .847 1. .00 91. .57 6

ATOM 200 OD1 ASP A 24 36. .945 8, .994 7, .900 1. .00 92. ,21 8

ATOM 201 OD2 ASP A 24 37. .680 7. .058 8, .756 1. .00 91. .67 8

ATOM 202 C ASP A 24 39. .631 10, .021 11. .305 1. .00 84. .31 6

ATOM 203 O ASP A 24 39, .173 9 .975 12, .458 1, .00 84, .64 8

ATOM 204 N ARG A 25 40. .935 9. .981 11, .029 1. .00 81. .75 7

ATOM 205 CA ARG A 25 41. .936 9. .898 12. .091 1. ,00 79. ,08 6

ATOM 206 CB ARG A 25 43. .309 9, .539 11, .527 1. .00 81. .87 6

ATOM 207 CG ARG A 25 43. .471 8, .100 11, .087 1, .00 86. .55 6

ATOM 208 CD ARG A 25 44. .960 7, .785 10, .851 1. .00 90. .81 6

ATOM 209 NE ARG A 25 45, .187 6, .380 10, .489 1. ,00 95, .61 7

ATOM 210 CZ ARG A 25 46 .388 5 .815 10 .345 1 .00 96 .85 6

ATOM 211 NHl ARG A 25 47, .495 6 .537 10 .530 1, .00 97, .46 7

ATOM 212 NH2 ARG A 25 46, .487 4, .522 10. .023 1. .00 97. .32 7

ATOM 213 C ARG A 25 42 .059 11 .201 12, .870 1 .00 75, .12 6

ATOM 214 O ARG A 25 42, .158 12 .283 12 .281 1 .00 75 .55 8

ATOM 215 N PRO A 26 42 .034 11 .112 14 .212 1 .00 70 .63 7

ATOM 216 CD PRO A 26 41 .636 9 .933 14 .999 1 .00 69, .09 6

ATOM 217 CA PRO A 26 42 .152 12 .281 15 .083 1 .00 67 .24 6

ATOM 218 CB PRO A 26 41 .802 11 .723 16 .460 1 .00 67 .68 6

ATOM 219 CG PRO A 26 40 .930 10 .565 16 .158 1 .00 68, .06 6

ATOM 220 C PRO A 26 43 .593 12 .762 15 .053 1 .00 64 .53 6

ATOM 221 O PRO A 26 44 .491 12 .000 14 .694 1 .00 63 .60 8

ATOM 222 N VAL A 27 43 .816 14 .020 15 .420 1 .00 61 .16 7

ATOM 223 CA VAL A 27 45 .168 14 .544 15 .476 1 .00 57 .20 6

ATOM 224 CB VAL A 27 45 .197 16 .079 15 .374 1 .00 56 .96 6

ATOM 225 CGI VAL A 27 .46 .535 16 .615 15 .872 1 .00 54 .60 6

ATOM 226 CG2 VAL A 27 44 .986 16 .496 13 .930 1 .00 55 .09 6

ATOM 227 C VAL A 27 45 .685 14 .114 16 .835 1 .00 55 .33 6

ATOM 228 O VAL A 27 45 .026 14 .328 17 .849 1 .00 53 .70 8

ATOM 229 N ALA A 28 46 .852 13 .484 16 .858 1 .00 54 .55 7

ATOM 230 CA ALA A 28 47 .405 13 .023 18 .118 1 .00 53 .25 6

ATOM 231 CB ALA A 28 48 .250 11 .785 17 .907 1 .00 52 .00 6

ATOM 232 C ALA A 28 48 .230 14 .117 18 .761 1 .00 52 .77 6

ATOM 233 O ALA A 28 49 .324 14 .451 18 .294 1 .00 52 .53 8 ATOM 234 N VAL A 29 47.683 14.672 19.837 1.00 51.33 7

ATOM 235 CA VAL A 29 48. 332 15. 730 20. 590 1. 00 49. 28 6

ATOM 236 CB VAL A 29 47. ,367 16. ,921 20. 845 1. 00 47. ,59 6

ATOM 237 CGI VAL A 29 48. ,056 17. ,985 21. 676 1. 00 44. ,30 6

ATOM 238 CG2 VAL A 29 46. ,891 17. ,497 19. 527 1. 00 44. ,21 6

ATOM 239 C VAL A 29 48. .782 15. .171 21. ,930 1. 00 49. .54 6

ATOM 240 O VAL A 29 48. ,014 14. 524 22. 635 1. 00 49. ,14 8

ATOM 241 N SER A 30 50. ,043 15. ,402 22. ,261 1. 00 49. ,54 7

ATOM 242 CA SER A 30 50. ,574 14. ,946 23. 523 1. 00 52. ,38 6

ATOM 243 CB SER A 30 51, .869 14. .163 23. ,309 1. ,00 51. .50 6

ATOM 244 OG SER A 30 52. .846 14, .945 22. ,645 1. ,00 56. .10 8

ATOM 245 C SER A 30 50. ,819 16. 187 24. 362 1. 00 54. ,25 6

ATOM 246 O SER A 30 51. .360 17. ,174 23. ,880 1. ,00 56. .41 8

ATOM 247 N VAL A 31 50. ,396 16. .134 25. ,618 1. 00 56. ,86 7

ATOM 248 CA VAL A 31 50, .543 17, .258 26. .531 1. ,00 58. .42 6

ATOM 249 CB VAL A 31 49. .170 17. ,768 27. 012 1. 00 58. ,48 6

ATOM 250 CGI VAL A 31 49. .338 19, .086 27. ,744 1. ,00 59. .95 6

ATOM 251 CG2 VAL A 31 48. .219 17. .910 25. ,835 1. ,00 56. .73 6

ATOM 252 C VAL A 31 51. .328 16. .803 27. ,747 1. ,00 59. .56 6

ATOM 253 O VAL A 31 51, .073 15, .729 28. .281 1. ,00 60, .85 8

ATOM 254 N SER A 32 52. .271 17. ,631 28. ,185 1. 00 61. ,06 7

ATOM 255 CA SER A 32 53, .105 17, .312 29. .338 1. ,00 60, .16 6

ATOM 256 CB SER A 32 54. .388 16. .619 28. .868 1. ,00 59. .88 6

ATOM 257 OG SER A 32 55 .294 16, .430 29, .937 1, ,00 60, .41 8

ATOM 258 C SER A 32 53, .465 18, .568 30. .116 1. .00 60, .19 6

ATOM 259 O SER A 32 54, .206 19, .416 29, .621 1. ,00 61, .87 8

ATOM 260 N LEU A 33 52, .946 18, .689 31, .333 1. ,00 58. .89 7

ATOM 261 CA LEU A 33 53, .256 19, .847 32. .170 1. ,00 57. .23 6

ATOM 262 CB LEU A 33 52 .112 20 .142 33, .142 1. .00 55, .20 6

ATOM 263 CG LEU A 33 50 .740 20, .363 32, .511 1. .00 54, .66 6

ATOM 264 CD1 LEU A 33 49 .762 20, .880 33, .543 1, ,00 51, .01 6

ATOM 265 CD2 LEU A 33 50, .880 21, .342 31, .373 1. .00 55, .39 6

ATOM 266 C LEU A 33 54, .518 19, .601 32, .979 1. ,00 56, .76 6

ATOM 267 0 LEU A 33 54 .697 18 .526 33, .533 1, .00 58, .14 8

ATOM 268 N LYS A 34 55, .394 20 .597 33, .028 1, .00 57, .17 7

ATOM 269 CA LYS A 34 56 .633 20, .512 33, .800 1. .00 57 .46 6

ATOM 270 CB LYS A 34 57 .865 20, .690 32, .910 1. ,00 60, .89 6

ATOM 271 CG LYS A 34 57 .940 19 .723 31 .738 1, .00 68 .80 6

ATOM 272 CD LYS A 34 58 .048 18 .249 32, .186 1, .00 73 .30 6

ATOM 273 CΞ LYS A 34 58 .071 17 .290 30 .961 1, .00 74, .90 6

ATOM 274 NZ LYS A 34 58 .210 15 .842 31, .340 1, .00 75 .55 7

ATOM 275 C LYS A 34 56 .522 21 .691 34, .741 1, .00 54 .81 6

ATOM 276 0 LYS A 34 56 .567 22 .834 34 .308 1 .00 55 .33 8

ATOM 277 N PHE A 35 56 .358 21 .422 36 .026 1, .00 52 .88 7

ATOM 278 CA PHE A 35 56 .215 22 .507 36 .976 1 .00 50 .00 6

ATOM 279 CB PHE A 35 55 .586 21 .993 38 .260 1 .00 45 .71 6

ATOM 280 CG PHE A 35 54 .186 21 .542 38 .072 1, .00 45 .07 6

ATOM 281 CD1 PHE A 35 53 .912 20 .256 37 .634 1 .00 45 .46 6

ATOM 282 CD2 PHE A 35 53 .133 22 .429 38 .252 1 .00 47 .46 6

ATOM 283 CE1 PHE A 35 52 .612 19 .848 37 .372 1 .00 45 .03 6

ATOM 284 CE2 PHE A 35 51 .819 22 .036 37 .990 1 .00 49 .48 6

ATOM 285 CZ PHE A 35 51 .560 20 .735 37 .547 1 .00 48 .14 6

ATOM 286 C PHE A 35 57 .494 23 .268 37 .247 1 .00 49 .05 6

ATOM 287 0 PHE A 35 58 .549 22 .687 37 .480 1 .00 48 .49 8

ATOM 288 N ILE A 36 57 .374 24 .588 37 .191 1 .00 46 .86 7

ATOM 289 CA ILE A 36 58 .492 25 .482 37 .393 1 .00 45 .55 6

ATOM 290 CB ILE A 36 58 .538 26 .551 36 .284 1 .00 43 .92 6

ATOM 291 CG2 ILE A 36 59 .771 27 .411 36 .433 1 .00 39 .03 6

ATOM 292 CGI ILE A 36 58 .526 25 .876 34 .917 1 .00 44 .17 6

ATOM 293 CDl ILE A 36 59 .671 24 .916 34 . 699 1 .00 46 .33 6

ATOM 294 C ILE A 36 58 .392 26 .181 38 .739 1 .00 46 .38 6 ATOM 295 O ILE A 36 59.405 26.580 39.318 1.00 45.40 8

ATOM 296 N ASN A 37 57. 176 26. 340 39. 244 1. 00 46. 13 7

ATOM 297 CA ASN A 37 57. ,023 27. 008 40. ,526 1. 00 46. ,27 6

ATOM 298 CB ASN A 37 57. 491 28. 462 40. 400 1. 00 46. 32 6

ATOM 299 CG ASN A 37 58. 009 29. 030 41. 707 1. 00 48. 59 6

ATOM 300 OD1 ASN A 37 57. .408 28. .844 42. .759 1. ,00 49. .38 8

ATOM 301 ND2 ASN A 37 59. ,124 29. 743 41. ,639 1. 00 46. ,71 7

ATOM 302 C ASN A 37 55. ,595 26. ,975 41. .046 1. 00 46. .17 6

ATOM 303 O ASN A 37 54. ,644 26. ,799 40. ,281 1. 00 44. ,02 8

ATOM 304 N ILE A 38 55. .465 27. .117 42. ,362 1. ,00 46. .64 7

ATOM 305 CA ILE A 38 54. ,173 27. .158 43. ,033 1. 00 48. .46 6

ATOM 306 CB ILE A 38 53. ,988 25. ,951 43. ,923 1. 00 47. ,34 6

ATOM 307 CG2 ILE A 38 52, .680 26, .066 44, .671 1. .00 49, .13 6

ATOM 308 CGI ILE A 38 53. ,983 24. ,697 43. .050 1. 00 48. ,40 6

ATOM 309 CDl ILE A 38 54. .079 23. .402 43. .791 1. ,00 47, .55 6

ATOM 310 C ILE A 38 54. ,245 28. .433 43. .847 1. ,00 50. .74 6

ATOM 311 O ILE A 38 54. .979 28. .505 44, .817 1. ,00 53, .13 8

ATOM 312 N LEU A 39 53. .485 29. .438 43, .433 1. ,00 53. .46 7

ATOM 313 CA LEU A 39 53. .527 30. .757 44. .045 1. ,00 55. .16 6

ATOM 314 CB LEU A 39 53. .350 31. .806 42. .952 1. . 00 54, .91 6

ATOM 315 CG LEU A 39 54. .330 31. .591 41, .800 1. ,00 57. .26 6

ATOM 316 CDl LEU A 39 54, .108 32, .647 40, .728 1, .00 54, .71 6

ATOM 317 CD2 LEU A 39 55. .757 31. .623 42. .341 1. ,00 54, .68 6

ATOM 318 C LEU A 39 52. .613 31, .098 45, .203 1. .00 56, .69 6

ATOM 319 O LEU A 39 53, .043 31, .750 46, .157 1. .00 59, .24 8

ATOM 320 N GLU A 40 51. .352 30. .715 45. .123 1. ,00 56. .60 7

ATOM 321 CA GLU A 40 50 .451 31 .019 46 .216 1, .00 58 .75 6

ATOM 322 CB GLU A 40 49. .617 32. .251 45, .920 1. ,00 59, .61 6

ATOM 323 CG GLU A 40 50, .426 33, .520 45, .821 1. .00 65 .69 6

ATOM 324 CD GLU A 40 49, .547 34, .752 45, .683 1. .00 69, .26 6

ATOM 325 OE1 GLU A 40 48 .747 34 .812 4 .715 1, .00 72 .53 8

ATOM 326 OE2 GLU A 40 49, .655 35, .659 46, .543 1, .00 69, .31 8

ATOM 327 C GLU A 40 49, .534 29, .863 46. .448 1. .00 60, .49 6

ATOM 328 O GLU A 40 49 .006 29 .275 45 .509 1 .00 62 .83 8

ATOM 329 N VAL A 41 49, .348 29, .525 47, .710 1, .00 60, .13 7

ATOM 330 CA VAL A 41 48 .474 28 .431 48 .049 1, .00 60 .14 6

ATOM 331 CB VAL A 41 49 .292 27, .230 48 .576 1, .00 59 .98 6

ATOM 332 CGI VAL A 41 48 .376 26 .185 49 .146 1 .00 59 .73 6

ATOM 333 CG2 VAL A 41 50 .118 26 .632 47 .444 1 .00 59 .26 6

ATOM 334 C VAL A 41 47. .510 28, .934 49 .109 1, .00 60 .58 6

ATOM 335 O VAL A 41 47, .864 29, .793 49, .934 1, .00 61, .24 8

ATOM 336 N ASN A 42 46, .283 28 .428 49 .059 1. .00 59 .54 7

ATOM 337^' CA ASN A 42 45 .267 28 .806 50 .024 1. .00 60 .72 6

ATOM 338 CB ASN A 42 44 .346 29-. .895 49 .463 1, .00 59, .36 6

ATOM 339 CG ASN A 42 43 .473 30 .530 50 .533 1 .00 59 .07 6

ATOM 340 OD1 ASN A 42 42 .811 29 .835 51 .303 1, .00 60 .43 8

ATOM 341 ND2 ASN A 42 43 .462 31 .856 50 .582 1. .00 57 .17 7

ATOM 342 C ASN A 42 44 .474 27 .535 50 .286 1, .00 62 .57 6

ATOM 343 O ASN A 42 43 .654 27 .107 49 .460 1, .00 62 .42 8

ATOM 344 N GLU A 43 44 .731 26 .921 51 .435 1 .00 63 .02 7

ATOM 345 CA GLU A 43 44 .045 25 .695 51 .792 1 .00 62 .62 6

ATOM 346 CB GLU A 43 44 .772 25 .004 52 .942 1 .00 65 .20 6

ATOM 347 CG GLU A 43 .44 .206 23 .642 53 .253 1 .00 67 .62 6

ATOM 348 CD GLU A 43 45: .088 22 .827 54 .174 1. .00 69 .40 6

ATOM 349 OE1 GLU A 43 44 .628 21 .739 54 .581 1 .00 71 .48 8

ATOM 350 OE2 GLU A 43 46 .228 23 .256 54 .479 1 .00 67 .83 8

ATOM 351 C GLU A 43 42 .595 25 .959 52 .169 1 .00 61 .53 6

ATOM 352 O GLU A 43 41 .755 25 .058 52 .086 1 .00 59 .68 8

ATOM 353 N ILE A 44 42 .309 27 .197 52 .575 1 .00 60 .06 7

ATOM 354 CA ILE A 44 40 .957 27 .580 52 .951 1 .00 60 .59 6

ATOM 355 CB ILE A 44 40 .923 28 .953 53 .632 1 .00 60 .98 6 ATOM 356 CG2 ILE A 44 39.469 29.,343 53..943 1.,00 61.,06 6

ATOM 357 CGI ILE A 44 41. 749 28. ,921 54. ,918 1. 00 61. ,51 6

ATOM 358 CDl ILE A 44 41. 119 28. ,117 56. ,022 1. ,00 61. ,37 6

ATOM 359 C ILE A 44 40. 069 27. ,660 51. .718 1. 00 61. ,06 6

ATOM 360 O ILE A 44 38. 942 27. ,148 51. ,708 1. 00 61. 53 8

ATOM 361 N THR A 45 40. ,581 28. .302 50. .674 1. ,00 60. .25 7

ATOM 362 CA THR A 45 39. 826 28. ,464 49. .426 1. 00 58. 34 6

ATOM 363 CB THR A 45 40. ,086 29, .844 48. .805 1. ,00 58. ,12 6

ATOM 364 OG1 THR A 45 41. .492 29. .992 48, .535 1. ,00 58, .85 8

ATOM 365 CG2 THR A 45 39. .632 30, .934 49, .762 1. .00 56, .98 6

ATOM 366 C THR A 45 40. ,139 27. .407 48. .374 1. ,00 56. .43 6

ATOM 367 O THR A 45 39. ,465 27. .328 47. .349 1. ,00 54. ,64 8

ATOM 368 N ASN A 46 41. .169 26, .607 48, .620 1. .00 55. .73 7

ATOM 369 CA ASN A 46 41. ,534 25. .563 47, .677 1. ,00 56. ,27 6

ATOM 370 CB ASN A 46 40. .390 24, .557 47, .560 1. .00 55. .82 6

ATOM 371 CG ASN A 46 40. .612 23, .327 48, .412 1. .00 56. .92 6

ATOM 372 ODl ASN A 46 39. .671 22, .621 48, .746 1. .00 55. .85 8

ATOM 373 ND2 ASN A 46 41. .866 23, .058 48, .754 1. .00 54. .55 7

ATOM 374 C ASN A 46 41, .869 26, .127 46, .299 1. ,00 56. .62 6

ATOM 375 O ASN A 46 41. .350 25, .659 45, .283 1. ,00 58. .80 8

ATOM 376 N GLU A 47 42. .744 27, .130 46, .275 1. ,00 54. .91 7

ATOM 377 CA GLU A 47 43, .156 27 .766 45 .044 1. .00 52. .39 6

ATOM 378 CB GLU A 47 42, .606 29 .183 44, .999 1, .00 50, .63 6

ATOM 379 CG GLU A 47 41. .107 29 .247 44, .938 1. .00 48. .77 6

ATOM 380 CD GLU A 47 40, .601 30, .675 44, .951 1. .00 53. .28 6

ATOM 381 OΞ1 GLU A 47 41. .370 31, .577 44, .568 1. .00 51. .68 8

ATOM 382 OE2 GLU A 47 39 .429 30 .902 45 .333 1, .00 58, .43 8

ATOM 383 C GLU A 47 44. .671 27, .776 44, .979 1. .00 52, ,87 6

ATOM 384 O GLU A 47 45 .347 28 .009 45 .981 1, .00 53, .20 8

ATOM 385 N VAL A 48 45, .208 27 .513 43 .797 1. ,00 53, .53 7

ATOM 386 CA VAL A 48 46 .656 27 .481 43 .619 1. .00 53, .36 6

ATOM 387 CB VAL A 48 47, .147 26, .043 43, .318 1. .00 53. .31 6

ATOM 388 CGI VAL A 48 48, .646 26 .029 43, .122 1. .00 55. .73 6

ATOM 389 CG2 VAL A 48 46 .781 25 .130 44 .456 1. .00 52, .72 6

ATOM 390 C VAL A 48 47, .108 28, .390 42, .484 1. .00 52. ,90 6

ATOM 391 O VAL A 48 46 .441 28 .504 41 .454 1. .00 54, .54 8

ATOM 392 N ASP A 49 48, .242 29 .046 42 .691 1, .00 52, .21 7

ATOM 393 CA ASP A 49 48 .818 29 .928 41 .692 1, .00 51, .57 6

ATOM 394 CB ASP A 49 49, .084 31 .291 42 .304 1, .00 52, .64 6 TOM 395 CG ASP A 49 49. .264 32 .352 41 .268 1. .00 53. .86 6

ATOM 396 ODl ASP A 49 49, .900 32 .051 40, .246 1. .00 54, .56 8

ATOM 397 OD2 ASP A 49 48, .779 33 .482 41 .474 1. .00 57, ,00 8

ATOM 398 C ASP A 49 50 .121 29 .241 41 .313 1, .00 50, .45 6

ATOM 399 O ASP A 49 51 .074 29 .254. 42 .075 1, .00 52, .15 8

ATOM 400 N VAL A 50 50 .155 28 .636 40 .135 1, .00 49, .83 7

ATOM 401 CA VAL A 50 51 .329 27 .893 39 .711 1, .00 49, .77 6

ATOM 402 CB VAL A 50 50 .992 26 .372 39 .723 1, .00 51 .61 6

ATOM 403 CGI VAL A 50 50 .095 26 .015 38 .531 1 .00 51 .90 6

ATOM 404 CG2 VAL A 50 52 .265 25 .539 39 .721 1, .00 53, .03 6

ATOM 405 C VAL A 50 51 .890 28 .290 38 .335 1 .00 49 .01 6

ATOM 406 O VAL A 50 51 .193 28 .878 37 .508 1, .00 50 .33 8

ATOM 407 N VAL A 51 53 .163 27 .974 38 .117 1, .00 46, .39 7

ATOM 408 CA VAL A 51 53 .863 28 .245 36 .861 1, .00 45, .41 6

ATOM 409 CB VAL A 51 55 .111 29 .134 37 .083 1, .00 43. .93 6

ATOM 410 CGI VAL A 51 55 .943 29 .182 35 .807 1. .00 42 .09 6

ATOM 411 CG2 VAL A 51 ^'54. .696 30 .536 37 .497 1, .00 41, .05 6

ATOM 412 C VAL A 51 54 .336 26 .899 36 .291 1 .00 46, .83 6

ATOM 413 O VAL A 51 54 .879 26 .063 37 .016 1 .00 47 .95 8

ATOM 414 N PHE A 52 54 .147 26 .684 34 .996 1 .00 45 .38 7

ATOM 415 CA PHE A 52 54 .560 25 .423 34 .402 1, .00 44 .58 6

ATOM 416 CB PHE A 52 53 .485 24 .373 34 .662 1. .00 44 .09 6 ATOM 417 CG PHE A 52 52.155 24.,718 34.,068 1.,00 43.,27 6

ATOM 418 CDl PHE A 52 51. ,857 24. ,393 32. ,758 1. ,00 42, ,79 6

ATOM 419 CD2 PHE A 52 51. ,211 25. .411 34. .805 1. .00 45, .35 6

ATOM 420 CE1 PHE A 52 50. ,643 24. ,755 32. ,194 1. ,00 41. ,86 6

ATOM 421 CE2 PHE A 52 49. ,991 25. ,776 34. ,240 1. ,00 45. ,03 6

ATOM 422 CZ PHE A 52 49, .712 25, .445 32, .933 1. ,00 41, .04 6

ATOM 423 C PHE A 52 54. .789 25. ,547 32. ,906 1. ,00 45. ,52 6

ATOM 424 O PHE A 52 54. .403 26. .536 32. .288 1. .00 46, .49 8

ATOM 425 N TRP A 53 55. .431 24. .541 32. .328 1. .00 45. .07 7

ATOM 426 CA TRP A 53 55. .662 24. ,527 30. ,898 1. .00 46. ,61 6

ATOM 427 CB TRP A 53 57. .043 24. ,000 30. ,573 1. .00 48. ,36 6

ATOM 428 CG TRP A 53 58. .137 24, .899 30. .983 1. ,00 50. ,29 6

ATOM 429 CD2 TRP A 53 59, .531 24, .604 30, .942 1. ,00 50. ,34 6

ATOM 430 CE2 TRP A 53 60. .213 25. ,755 31. ,386 1. ,00 51. ,89 6

ATOM 431 CE3 TRP A 53 60, .274 23, .473 30. ,570 1. ,00 52. .05 6

ATOM 432 CDl TRP A 53 58. .024 26. ,175 31, ,436 1. .00 50. .84 6

ATOM 433 NE1 TRP A 53 59. .267 26, .700 31, .682 1. ,00 52. ,12 7

ATOM 434 CZ2 TRP A 53 61. .605 25, .817 31, .470 1. ,00 53, ,79 6

ATOM 435 CZ3 TRP A 53 61, .660 23. .527 30. ,649 1. .00 53. ,82 6

ATOM 436 CH2 TRP A 53 62. .314 24. .697 31. . 099 1. ,00 55. .14 6

ATOM 437 C TRP A 53 54. .644 23. .599 30. .285 1. .00 47. .55 6

ATOM 438 O TRP A 53 54. .645 22, .410 30, .564 1, .00 49. .29 8

ATOM 439 N GLN A 54 53, .765 24, .139 29, .457 1. .00 47, .91 7

ATOM 440 CA GLN A 54 52, .765 23, .312 28, .825 1. .00 48, .38 6

ATOM 441 CB GLN A 54 51, .517 24, .132 28, .529 1, .00 47, .98 6

ATOM 442 CG GLN A 54 50, .322 23, .309 28, .095 1. .00 50. ,36 6

ATOM 443 CD GLN A 54 49 .001 24 .016 28 .375 1, .00 54 .00 6

ATOM 444 OE1 GLN A 54 48, .697 24, .360 29. .515 1, .00 53. .48 8

ATOM 445 NE2 GLN A 54 48, .209 24, .231 27, .335 1. .00 57, .12 7

ATOM 446 C GLN A 54 53, .378 22, .755 27, .555 1. .00 49, .13 6

ATOM 447 O GLN A 54 53 .095 23 .203 26, .453 1, ,00 50 .86 8

ATOM 448 N GLN A 55 54, .251 21, .779 27. .738 1. .00 50, .50 7

ATOM 449 CA GLN A 55 54, .937 21, .122 26. .641 1. ,00 52, .90 6

ATOM 450 CB GLN A 55 55 .995 20 .200 27 .234 1, .00 58 .12 6

ATOM 451 CG GLN A 55 56, .699 19. .288 26. .263 1. ,00 66. ,05 6

ATOM 452 CD GLN A 55 57 .909 18 .634 26, .907 1, .00 71 .07 6

ATOM 453 OE1 GLN A 55 57 .890 18 .307 28, .107 1 .00 73 .93 8

ATOM 454 NE2 GLN A 55 58, .969 18 .442 26, .123 1, .00 72, .99 7

ATOM 455 C GLN A 55 53. .939 20 .353 25, .774 1, .00 51, .30 6

ATOM 456 O GLN A 55 53 .451 19 .293 26, .151 1 .00 50 .67 8

ATOM 457 N THR A 56 53, .648 20 .907 24, .604 1, . 00 49, .14 7

ATOM 458 CA THR A 56 52 .690 20 .325 23, .684 1 .00 46 .69 6

ATOM 459 CB THR A 56 51 .597 21 .347 23 .342 1 .00 45 .67 6

ATOM 460 OG1 THR A 56 51 .138 21 .969 24 .541 1 .00 45 .84 8

ATOM 461 CG2 THR A 56 50 .426 20 .673 22 .666 1 .00 45 .93 6

ATOM 462 C THR A 56 53 .344 19 .878 22 .389 1 .00 46 .05 6

ATOM 463 O THR A 56 54 .286 20 .503 21 .917 1. .00 46 .13 8

ATOM 464 N THR A 57 52 .^'836 18 .796 21 .812 1 .00 44 .22 7

ATOM 465 CA THR A 57 53 .384 18 .286 20 .569 1 . 00 44 .65 6

ATOM 466 CB THR A 57 54 .511 17 .270 20 .823 1 .00 44 .59 6

ATOM 467 OG1 THR A 57 55 .593 17 .914 21 .499 1 .00 42 .38 8

ATOM 468 CG2 THR A 57 55 .036 16 .733 19 .512 1 .00 49 .11 6

ATOM 469 C THR A 57 52 .316 17 .627 19 .721 1 .00 43 .97 6

ATOM 470 O THR A 57 51 .377 17 .039 20 .239 1 .00 44 .62 8

ATOM 471 N TRP A 58 52 .452 17 .753 18 .410 1 .00 42 .72 7

ATOM 472 CA TRP A 58 51 .502 17 .153 17 .489 1 .00 44 .75 6

ATOM 473 CB TRP A 58 50 .139 ^• 17 .883 17 .529 1 .00 42 .24 6

ATOM 474 CG TRP A 58 50 .130 19 .267 16 .967 1 .00 40 .43 ^' 6

ATOM 475 CD2 TRP A 58 50 .427 20 .473 17 .668 1 .00 39 .55 6

ATOM 476 CE2 TRP A 58 50 .354 21 .521 16 .735 1 .00 41 .08 6

ATOM 477 CΞ3 TRP A 58 50 .755 20 .770 18 .995 1 .00 36 .98 6

-80

ATOM 478 CDl TRP A 58 49. 887 19. 624 15. 677 1. 00 39. 98 6

ATOM 479 NEl TRP A 58 50. 019 20. 971 15. 527 1. 00 41. 55 7

ATOM 480 CZ2 TRP A 58 50. 599 22. 850 17. 084 1. 00 40. 32 6

ATOM 481 CZ3 TRP A 58 50. 997 22. 081 19. 341 1. 00 37. 03 6

ATOM 482 CH2 TRP A 58 50. 919 23. 109 18. 389 1. 00 38. 53 6

ATOM 483 C TRP A 58 52. 112 17. 184 16. 098 1. 00 47. 09 ^■ 6

ATOM 484 O TRP A 58 53. 226 17. 675 15. 915 1. 00 47. 06 8

ATOM 485 N SER A 59 51. 390 16. 670 15. 115 1. 00 48. 64 7

ATOM 486 CA SER A 59 51. 933 16. 631 13. 782 1. 00 50. 92 6

ATOM 487 CB SER A 59 52. 245 15. 187 13. 435 1. 00 53. 25 6

ATOM 488 OG SER A 59 53. 191 15. 109 12. 389 1. 00 62. 80 8

ATOM 489 C SER A 59 51. 020 17. 229 12. 735 1. 00 52. 80 6

ATOM 490 O SER A 59 49. 828 16. 942 12. 696 1. 00 53. 05 8

.ATOM 491 N ASP A 60 51. 602 18. ,065 11. 881 1. 00 55. 45 7

ATOM 492 CA ASP A 60 50. 881 18. 721 10. 792 1. 00 57. 44 6

ATOM 493 CB ASP A 60 50. 741 20. 221 11. 071 1. 00 57. 33 6

ATOM 494 CG ASP A 60 49. 856 20. ,936 10. 058 1. 00 57. ,43 6

ATOM 495 ODl ASP A 60 49. 776 20. ,486 8. 896 1. 00 57. 47 8

ATOM 496 OD2 ASP A 60 49. 256 21. ,967 10. 424 1. 00 56. ,76 8

ATOM 497 C ASP A 60 51. 726 18. ,510 9. 541 1. 00 59. 20 6

ATOM 498 O ASP A 60 52. 679 19. ,245 9. 304 1. 00 58. ,82 8

ATOM 499 N ARG A 61 51. ,372 17, ,503 8. ,748 1. 00 61. ,30 7

ATOM 500 CA ARG A 61 52. ,115 17, ,181 7. ,533 1. ,00 63. ,09 6

ATOM 501 CB ARG A 61 51. .643 15, .845 6. ,958 1. ,00 67, .23 6

ATOM 502 CG ARG A 61 52. 191 14. ,594 7. ,653 1. 00 72. ,92 6

ATOM 503 CD ARG A 61 51, .883 13. .355 6. ,786 1. ,00 81. ,01 6

ATOM 504 NE ARG A 61 52. ,441 12, .091 7. ,291 1. ,00 85, .79 7

ATOM 505 CZ ARG A 61 52. ,320 10, .917 6, ,660 1. ,00 87, .50 6

ATOM 506 NHl ARG A 61 51, .665 10 .843 5, .501 1, .00 88 .31 7

ATOM 507 NH2 ARG A 61 52 .852 9 .815 7, .179 1, .00 87 .74 7

ATOM 508 C ARG A 61 52 .073 18 .238 6 .430 1 .00 61 .94 6

ATOM 509 0 ARG A 61 52, ,927 18, .225 5, .550 1. .00 61. .39 8

ATOM 510 N THR A 62 51, .095 1 .141 6, .461 1, .00 60, .78 7

ATOM 511 CA THR A 62 51, .017 20 .175 5 .434 1, .00 59 .76 6

ATOM 512 CB THR A 62 49 .666 20 .952 5, .483 1, .00 60 .01 6

ATOM 513 OG1 THR A 62 49 .582 21 .720 6 .689 1 .00 62 .71 8

ATOM 514 CG2 THR A 62 48 .500 20 .000 5 .442 1, .00 59 .86 6

ATOM 515 C THR A 62 52 .172 21 .171 5 .616 1 .00 58 .73 6

ATOM 516 O THR A 62 52 .400 22 .044 4 .774 1 .00 59 .33 8

ATOM 517 N LEU A 63 52 .898 21 .031 6 .720 1 .00 56 .50 7

ATOM 518 CA LEU A 63 54 .029 21 .903 7 .020 1 .00 55 .97 6

ATOM 519 CB LEU A 63 54 .088 22 .205 8 .521 1 .00 53 .19 6

ATOM 520 CG LEU A 63 52 .866 22 .837 9 .174 1 .00 52 .76 6

ATOM 521 CDl LEU A 63 53 .074 22 .909 10 .672 1 .00 51 .73 6

ATOM 522 CD2 LEU A 63 52 .629 24 .217 8 .589 1 .00 53 .34 6

ATOM 523 C LEU A 63 55 .351 21 .264 6 .603 1 .00 55 .80 6

ATOM 524 O LEU A 63 56 .366 21 .947 6 .509 1 .00 54 .36 8

ATOM 525 N ALA A 64 55 .332 19 .952 6 .368 1 .00 56 .30 7

ATOM 526 CA ALA A 64 56 .532 19 .207 5 .987 1 .00 56 .99 6

ATOM 527 CB ALA A 64 56 .194 17 .744 5 .810 1 .00 54 .20 6

ATOM 528 C ALA A 64 57 .176 19 .745 4 .715 1 .00 59 .20 6

ATOM 529 O ALA A 64 56 .487 20 .224 3 .816 1 .00 60 .08 8

ATOM 530 N TRP A 65 58 .502 19 .646 4 .651 1 .00 60 .65 7

ATOM 531 CA TRP A 65 59 .295 20 .104 3 .506 1 .00 62 .47 6

ATOM 532 CB TRP A 65 59 .623 21 .588 3 .667 1 .00 59 .37 6

ATOM 533 CG TRP A 65 60 .773 21 .870 4 .613 1 .00 56 .94 6

ATOM 534 CD2 TRP A 65 60 .685 22 .167 6 .020 1 .00 56 .89 6

ATOM 535 CE2 TRP A 65 62 .001 22 .424 6 .475 1 .00 55 .08 6

ATOM 536 CΞ3 TRP A 65 59 .622 22 .245 6 .938 1 .00 54 .01 6

ATOM 537 CDl TRP A 65 62 .097 21 .947 4 .292 1 .00 55 .45 6

ATOM 538 NEl TRP A 65 62 .838 22 .282 5 .400 1 .00 53 .98 7 11

ATOM 539 CZ2 TRP A 65 62. 286 22. 757 7. 808 1. 00 52. 03 6

ATOM 540 CZ3 TRP A 65 59. 910 22. 577 8. 266 1. 00 53. 82 6

ATOM 541 CH2 TRP A 65 61. 232 22. 829 8. 684 1. 00 51. 71 6

ATOM 542 C TRP A 65 60. 603 19. 297 3. 445 1. 00 65. 72 6

ATOM 543 O TRP A 65 61. 091 18. 825 4. ,479 1. 00 66. 89 8

ATOM 544 N ASN A 66 61. 181 19. ,138 2. ,255 1. 00 68. 69 7

ATOM 545 CA ASN A 66 62. 431 18. .^'371 2. ,149 1. 00 71. 84 6

ATOM 546 CB ASN A 66 62. ,735 17. .983 0. ,689 1. 00 73. ,23 6

ATOM 547 CG ASN A 66 63. 968 17. 084 0. 568 1. 00 76. 18 6

ATOM 548 ODl ASN A 66 64. 473 16. ,822 -0. ,541 1. 00 76. 68 8

ATOM 549 ND2 ASN A 66 64. ,463 16. ,606 1. ,715 1. 00 76. ,39 7

ATOM 550 C ASN A 66 63. 581 19. 199 2. ,723 1. 00 71. 96 6

ATOM 551 O ASN A 66 63. ,902 20. .279 2. .217 1. 00 72. ,02 8

ATOM 552 N SER A 67 64. .197 18. .690 3. .784 1. ,00 72, ,09 7

ATOM 553 CA SER A 67 65. ,292 19, ,403 4. .435 1. 00 72. ,65 6

ATOM 554 CB SER A 67 65. .063 19. ,425 5. .943 1. ,00 72. ,61 6

ATOM 555 OG SER A 67 64. ,969 18. .105 6, .449 1. ,00 70. ,09 8

ATOM 556 C SER A 67 66, .655 18, .794 4, .177 1. ,00 73. .27 6

ATOM 557 0 SER A 67 67. ,576 19. ,031 4. ,961 1. 00 72. ,43 8

ATOM 558 N SER A 68 66. .799 18. .026 3. .097 1. ,00 74. .60 7

ATOM 559 CA SER A 68 68, .082 17. .370 2 .825 1. ,00 76. ,38 6

ATOM 560 CB SER A 68 68. .006 16, .490 1, .564 1. ,00 75. ,57 6

ATOM 561 OG SER A 68 67, .870 17. .265 0, .386 1. ,00 75. .20 8

ATOM 562 C SER A 68 69, .222 18, .380 2, .707 1, ,00 77. .15 6

ATOM 563 O SER A 68 70. .288 18. .201 3, ,300 1. ,00 77. .04 8

ATOM 564 N HIS A 69 68. .992 19, .451 1, ,962 1. ,00 78. ,21 7

ATOM 565 CA HIS A 69 70, .015 20, .479 1, .804 1. ,00 79. ,62 6

ATOM 566 CB HIS A 69 70. .445 20. .578 0, .341 1. ,00 84. ,04 6

ATOM 567 CG HIS A 69 71 .007 19 .302 -0 .196 1. .00 88, .01 6

ATOM 568 CD2 HIS A 69 72, .208 19, .022 -0, .759 1. ,00 89, .20 6

ATOM 569 NDl HIS A 69 70. .332 18. .100 -0, .110 1. .00 89. .31 7

ATOM 570 CE1 HIS A 69 71 .096 17 .133 -0. .589 1. .00 90, .18 6

ATOM 571 NE2 HIS A 69 72, .240 17, .666 -0, .988 1. .00 90, .99 7

ATOM 572 C HIS A 69 69 .441 21 .799 2 .279 1, .00 77 .78 6

ATOM 573 0 HIS A 69 69 .473 22, .803 1 .561 1. .00 77 .92 8

ATOM 574 N SER A 70 68 .896 21 .766 3. .496 1, .00 75 .27 7

ATOM 575 CA SER A 70 68 .300 22 .931 4 .141 1, .00 72 .21 6

ATOM 576 CB SER A 70 67 .013 23 .316 3. .421 1. .00 72 .74 6

ATOM 577 OG SER A 70 66 .368 22 .158 2 .919 1, .00 74 .05 8

ATOM 578 C SER A 70 68. .031 22 .563 5 .595 1. .00 69, .35 6

ATOM 579 O SER A 70 68 .138 21 .384 5 .962 1, ,00 70 .38 8

ATOM 580 N PRO A 71 67 .710 23 .563 6 .450 1, .00 66 .44 7

ATOM 581 CD PRO A 71 67 .819 24 .998 6 .134 1, .00 64 .03 6

ATOM 582 CA PRO A 71 67 .422 23 .385 7 .883 1, .00 64 .80 6

ATOM 583 CB PRO A 71 67 .106 24 .805 8 .334 1, .00 63 .49 6

ATOM 584 CG PRO A 71 68 .031 25 .608 7 .498 1, .00 61 .83 6

ATOM 585 C PRO A 71 66 .295 22 .395 8 .223 1 .00 63 .99 6

ATOM 586 O PRO A 71 65 .314 22 .289 7. .496 1, .00 63 .63 8

ATOM 587 N ASP A 72 66 .434 21 .679 9 .333 1 .00 63 .39 7

ATOM 588 CA ASP A 72 65 .424 20 .701 9 .734 1 .00 63 .43 6

ATOM 589 CB ASP A 72 66 .056 19 .634 10 .617 1 . 00 65 .69 6

ATOM 590 CG ASP A 72 67 .229 18 .974 9 .959 1 .00 70 .53 6

ATOM 591 ODl ASP A 72 66 .985 18 .216 8 .988 1 .00 73 .68 8

ATOM 592 OD2 ASP A 72 68 .389 • 19 .218 10 .390 1 .00 71 .00 8

ATOM 593 C ASP A 72 64 .307 21 .356 10 .520 1 .00 62 .20 6

ATOM 594 O ASP A 72 63 .164 20 .878 10 .520 1 .00 61 .88 8

ATOM 595 N GLN A 73 64 .653 22 .457 11 .175 1 .00 59 .83 7

ATOM 596 CA GLN A 73 63 .738 23 .186 12 .041 1 .00 59 .45 6

ATOM 597 CB GLN A 73 64 .083 22 .901 13 .489 1 .00 60 .33 6

ATOM 598 CG GLN A 73 63 .720 21 .569 14 .035 1 .00 63 .59 6

ATOM 599 CD GLN A 73 64 .224 21 .462 15 .459 1 .00 68 .15 6 ATOM 600 OE1 GLN A 73 65.425 21.595 15.699 1.00 70.61 8

ATOM 601 NE2 GLN A 73 63. 316 21. 249 16. ,416 1. 00 69. 73 7

ATOM 602 C GLN A 73 63. .779 24. ,703 11. .886 1. ,00 57. .04 6

ATOM 603 O GLN A 73 64. 798 25. 280 11. 490 1. 00 58. 19 8

ATOM 604 N VAL A 74 62. 670 25. 336 12. .243 1. 00 52. 68 7

ATOM 605 CA VAL A 74 62. ,557 26. ,782 12. ,211 1. 00 50. 24 6

ATOM 606 CB VAL A 74 62. ,036 27. ,279 10. .859 1. 00 48. 70 6

ATOM 607 CGI VAL A 74 63. ,066 27. ,034 9. .794 1. ,00 49. 74 6

ATOM 608 CG2 VAL A 74 60. 738 26. ,584 10. ,515 1. 00 47. 98 6

ATOM 609 C VAL A 74 61, ,580 27. .201 13. .310 1. .00 49. ,74 6

ATOM 610 O VAL A 74 60. ,756 26. ,401 13. .754 1. ,00 48. , 96 8

ATOM 611 N SER A 75 61. ,691 28. ,442 13. ,769 1. 00 47. 62 7

ATOM 612 CA SER A 75 60, .792 28. .954 14. .787 1, .00 44. ,06 6

ATOM 613 CB SER A 75 61. ,525 29. ,902 15. .728 1. ,00 44. ,67 6

ATOM 614 OG SER A 75 62. ,241 29. ,188 16. .710 1. ,00 46. ,37 8

ATOM 615 C SER A 75 59. ,668 29. .688 14. .084 1. .00 43. ,07 6

ATOM 616 O SER A 75 59, .894 30, .657 13 .358 1. .00 42, .11 8

ATOM 617 N VAL A 76 58. .451 29. .214 14. .307 1. .00 42. .71 7

ATOM 618 CA VAL A 76 57. .272 29. .792 13. .687 1. .00 43. ,33 6

ATOM 619 CB VAL A 76 56, .482 28. .711 12, .936 1. .00 44, ,34 6

ATOM 620 CGI VAL A 76 55. .247 29. .315 12, .298 1. .00 44, .97 6

ATOM 621 CG2 VAL A 76 57. .359 28. .058 11, .894 1, .00 43. .12 6

ATOM 622 C VAL A 76 56. .335 30. .436 14, ,704 1. ,00 44. .16 6

ATOM 623 O VAL A 76 56, .093 29, .882 15, .773 1, .00 45, .89 8

ATOM 624 N PRO A 77 55, .798 31, .624 14 .388 1, .00 43. .19 7

ATOM 625 CD PRO A 77 56, .162 32. .556 13. .311 1. ,00 41. ,24 6

ATOM 626 CA PRO A 77 54, .884 32. .266 15, ,334 1, ,00 41. ,49 6

ATOM 627 CB PRO A 77 54, .619 33, .615 14, .691 1. ,00 41. .13 6

ATOM 628 CG PRO A 77 55. ,886 33. .884 13, ,950 1. ,00 41. ,89 6

ATOM 629 C PRO A 77 53. ,617 31. .439 15. .453 1. .00 40. ,82 6

ATOM 630 O PRO A 77 53, .112 30. .919 14 .471 1. .00 39, .55 8

ATOM 631 N ILE A 78 53, ,116 31, .318 16, .671 1. .00 42. ,42 7

ATOM 632 CA ILE A 78 51 .908 30 .556 16 .959 1, .00 42, .14 6

ATOM 633 CB ILE A 78 51, .526 30 .751 18 .441 1, .00 42, .09 6

ATOM 634 CG2 ILE A 78 50, ,105 30, .357 18. .712 1. .00 43. .53 6

ATOM 635 CGI ILE A 78 • 52 .464 29 .921 19- .285 1 .00 43 .22 6

ATOM 636 CDl ILE A 78 ^' 52, ,585 28. .513 18, ,784 1. .00 43. .92 6

ATOM 637 C ILE A 78 50 .749 30 .942 16 .057 1. .00 43, .58 6

ATOM 638 O ILE A 78 49 .985 30 .096 15 .624 1 .00 45, .64 8

ATOM 639 N SER A 79 50, .642 32, .229 15 .768 1. .00 43. .79 7

ATOM 640 CA SER A 79 49. .588 32 .767 14 .918 1, .00 44 .38 6

ATOM 641 CB SER A 79 49 .666 34 .292 14 .934 1 .00 44 .81 6

ATOM 642 OG _. SER A 79 50 .972 34 .732 14 .584 1 .00 45 .88 8

ATOM 643 C SER A 79 49, .590 32, .295 13 .465 1 .00 43, .50 6

ATOM 644 O SER A 79 48 .607 32 .498 12 .758 1 .00 42 .80 8

ATOM 645 N SER A 80 50 .685 31 .683 13 .016 1 .00 42 .62 7

ATOM 646 CA SER A 80 50 .774 31 .216 11 .639 1. .00 42. .84 6

ATOM 647 CB SER A 80 52 .137 31 .555 11 .043 1 .00 44 .68 6

ATOM 648 OG SER A 80 52, .308 32 .956 10 .932 1 .00 51 .59 8

ATOM 649 C SER A 80 50 .534 29 .726 11 .502 1 .00 44 .69 6

ATOM 650 O SER A 80 50 .596 29 .184 10 .402 1 .00 43 .97 8

ATOM 651 N LEU A 81 50 .248 29 .068 12 .620 1 .00 45 .13 7

ATOM 652 CA LEU A 81 50 .003 27 .631 12 .631 1 .00 41 .19 6

ATOM 653 . CB LEU A 81 51 .061 26 .926 13 .467 1 .00 39 .92 6

ATOM 654 CG LEU A 81 52 .534 27 .167 13 .185 1 .00 41 .52 6

ATOM 655 CDl LEU A 81 53 .356 26 .677 14 .355 1 .00 39 .70 6

ATOM 656 CD2 LEU A 81 52 .922 26 .464 11 .918 1 .00 42 .52 6

ATOM 657 C LEU A 81 48 .672 27 .340 13 .272 1 .00 39 .47 6

ATOM 658 0 LEU A 81 48 .089 28 .197 13 .921 1 .00 40 .21 8

ATOM 659 N TRP A 82 48 .191 26 .122 13 .081 1 .00 38 .46 7

ATOM 660 CA TRP A 82 46 .965 25 .694 13 .720 1 .00 37 .32 6 ATOM 661 CB TRP A 82 46.346 24.,494 13.006 1.00 36.83 6

ATOM 662 CG TRP A 82 45. 274 23. ,818 13. 829 1. 00 40. 60 6

ATOM 663 CD2 TRP A 82 45. ,459 22. .741 14. ,757 1. 00 39. .63 6

ATOM 664 CE2 TRP A 82 44. 213 22. 499 15. 369 1. 00 38. 33 6

ATOM 665 CE3 TRP A 82 46. 560 21. 961 15. 132 1. 00 40. 54 6

ATOM 666 CDl TRP A 82 43. ,948 24, ,170 13. ,914 1. 00 39. ,43 6

ATOM 667 NEl TRP A 82 43. 311 23. ,383 14. ,839 1. 00 39. ,00 7

ATOM 668 CZ2 TRP A 82 44. .040 21, .511 16, .332 1. 00 38. .94 6

ATOM 669 CZ3 TRP A 82 46. .388 20. .982 16. .088 1. 00 39. ,99 6

ATOM 670 CH2 TRP A 82 45. ,135 20. .764 16. ,678 1. 00 39. .88 6

ATOM 671 C TRP A 82 47. ,485 25. ,241 15. ,064 1. 00 36. ,99 6

ATOM 672 0 TRP A 82 48. ,559 24, .661 15. ,142 1. 00 38. ,93 8

ATOM 673 N VAL A 83 46, .744 25. ,503 16. ,123 1. ,00 37. .43 7

ATOM 674 CA VAL A 83 47. ,179 25. .086 17, .437 1. 00 37. .48 6

ATOM 675 CB VAL A 83 47. ,729 26. .300 18. ,209 1, ,00 37. .40 6

ATOM 676 CGI VAL A 83 47. ,901 25. .984 19. ,655 1. 00 43. ,51 6

ATOM 677 CG2 VAL A 83 49, ,054 26, .688 17. .644 1. ,00 37, .34 6

ATOM 678 C VAL A 83 46, .011 24 .437 18, .175 1. .00 39, .74 6

ATOM 679 O VAL A 83 44. .858 24, .823 17. .997 1. ,00 42. .50 8

ATOM 680 N PRO A 84 46. .290 23, .408 18, .982 1, ,00 39, .54 7

ATOM 681 CD PRO A 84 47. .594 22, ,745 19. .134 1. 00 41. .22 6

ATOM 682 CA PRO A 84 45, .263 22, .701 19. .752 1. ,00 38, .54 6

ATOM 683 CB PRO A 84 46, .079 21 .690 20 .558 1. ,00 39, .94 6

ATOM 684 CG PRO A 84 47, .202 21 .381 19. .663 1, ,00 41 .42 6

ATOM 685 C PRO A 84 44, .509 23 .663 20, .658 1. ,00 36, .09 6

ATOM 686 0 PRO A 84 45, .121 24, .469 21, .342 1. ,00 35, .57 8

ATOM 687 N ASP A 85 43 .186 23 .576 20 .668 1, .00 32 .88 7

ATOM 688 CA ASP A 85 42 .397 24 .458 21 .505 1. ,00 34 .36 6

ATOM 689 CB ASP A 85 41 .014 24 .668 20 .898 1, .00 35 .14 6

ATOM 690 CG ASP A 85 40, .268 23, .381 20, .696 1. ,00 37, .78 6

ATOM 691 ODl ASP A 85 40 .897 22 .388 20 .290 1. .00 40 .24 8

ATOM 692 OD2 ASP A 85 39 .050 23 .367 20 .927 1. .00 37 .65 8

ATOM 693 C ASP A 85 42, .277 23, .906 22, .910 1. .00 35, .33 6

ATOM 694 O ASP A 85 41 .180 23 .726 23 .420 1, .00 38 .82 8

ATOM 695 N LEU A 86 43, .418 23, .644 23, .528 1. ,00 32, .24 7

ATOM 696 CA LEU A 86 43 .459 23 .106 24 .869 1. ,00 35 .18 6

ATOM 697 CB LEU A 86 44 .878 22 .670 25 .208 1. ,00 34, .63 6

ATOM 698 CG LEU A 86 45 .435 21 .585 24 .311 1. ,00 35, .36 6

ATOM 699 CDl LEU A 86 46 .842 21 .241 24 .749 1. .00 34 .84 6

ATOM 700 CD2 LEU A 86 44 .530 20 .376 24 .386 1, ,00 35 .68 6

ATOM 701 C LEU A 86 42 .973 24 .086 25 .925 1, .00 36 .01 6

ATOM 702 O LEU A 86 43 .141 25 .283 25 .800 1, .00 37 .75 8

ATOM 703 N ALA A 87 42 .378 23 .556 26 .979 1, .00 38 .03 7

ATOM 704 CA ALA A 87 41 .870 24 .369 28 .060 1, .00 38 .29 6

ATOM 705 CB ALA A 87 40 .428 24 .674 27 .811 1, .00 36 .17 6

ATOM 706 C ALA A 87 42 .022 23 .605 29 .371 1, .00 41 .08 6

ATOM 707 0 ALA A 87 41 .798 22 .399 29 .407 1, .00 43 .90 8

ATOM 708 N ALA A 88 42 .431 24 .290 30 .436 1, .00 39 .68 7

ATOM 709 CA ALA A 88 42 .558 23 .639 31 .726 1. .00 38 .37 6

ATOM 710 CB ALA A 88 43 .586 24 .337 32 .571 1 .00 34 .88 6

ATOM 711 C ALA A 88 41 .180 23 .729 32 .376 1 .00 40 .65 6

ATOM 712 0 ALA A 88 40 .778 24 .780 32 .847 1 .00 40 .29 8

ATOM 713 N TYR A 89 40 .460 22 .613 32 .371 1, .00 42 .49 7

ATOM 714 CA TYR A 89 39 .116 22 .502 32 .934 1, .00 44 .24 6

ATOM 715 CB TYR A 89 38 .727 21 .023 33 .052 1. .00 46 .70 6

ATOM 716 CG TYR A 89 38 .641 20 .286 31 .725 1 .00 51 .62 6

ATOM 717 CDl TYR A 89 38 .462 18 .902 31 .684 1 .00 54 .35 6

ATOM 718 CE1 TYR A 89 38 .353 18 .222 30 .466 1, .00 56 .33 6

ATOM 719 CD2 TYR A 89 38 .711 20 .968 30 .511 1 .00 51 .86 6

ATOM 720 CE2 TYR A 89 38 .604 20 .297 29 .302 1 .00 53 .71 6

ATOM 721 CZ TYR A 89 38 .424 18 .927 29 .286 1 .00 55 .54 6 ATOM 722 OH TYR A 89 38.296 18.257 28.093 1.00 59.35- 8

ATOM 723 C TYR A 89 38. 888 23. 185 34. 280 1. 00 43. 81 6

ATOM 724 O TYR A 89 37. 808 23. ,735 34. ,518 1. 00 41. ,70 8

ATOM 725 N ASN A 90 39. ,880 23. ,149 35. ,167 1. 00 43. ,90 7

ATOM 726 CA ASN A 90 39. 709 23. 781 36. 473 1. 00 43. 12 6

ATOM 727 CB ASN A 90 39. 976 22. 770 37. ,598 1. 00 40. 92 6

ATOM 728 CG ASN A 90 41. 340 22. 156 37. ,517 1. 00 42. ,04 6

ATOM 729 ODl ASN A 90 41. ,770 21. ,721 36. .456 1. ,00 43. ,62 8

ATOM 730 ND2 ASN A 90 42. 033 22. 102 38. ,646 1. 00 43. ,25 7

ATOM 731 C ASN A 90 40. 550 25. ,042 36. ,655 1. ,00 44. ,35 6

ATOM 732 O ASN A 90 40. ,881 25. ,434 37. ,769 1. ,00 46. ,42 8

ATOM 733 N ALA A 91 40. 902 25. ,673 35. ,543 1. 00 45. ,44 7

ATOM 734 CA ALA A 91 41. ,660 26. ,912 35. ,591 1. ,00 45. ,36 6

ATOM 735 CB ALA A 91 42. ,130 27. ,308 34. .206 1. ,00 44. .43 6

ATOM 736 C ALA A 91 40. ,680 27. ,940 36. .136 1. ,00 45. .00 6

ATOM 737 O ALA A 91 39. ,522 28. ,000 35. .729 1. ,00 43. .71 8

ATOM 738 N ILE A 92 41. ,164 28, ,750 37. ,064 1. ,00 46. .47 7

ATOM 739 CA ILE A 92 40. .359 29. .753 37. .734 1. .00 46. .18 6

ATOM 740 CB ILE A 92 40. .674 29. .673 39. .232 1, .00 47. .56 6

ATOM 741 CG2 ILE A 92 41. .595 30. .797 39. ,634 1, ,00 50. .92 6

ATOM 742 CGI ILE A 92 39. .409 29. .713 40. .055 1. ,00 50. ,52 6

ATOM 743 CDl ILE A 92 39. .711 29. .795 41, .547 1. ,00 51, .82 6

ATOM 744 C ILE A 92 . 40. .659 31, ,157 37. .177 1. .00 45. .80 6

ATOM 745 O ILE A 92 39. .996 32, .134 37, ,518 1. .00 45. .79 8

ATOM 746 N SER A 93 41. ,666 31. ,237 36. ,317 1. ,00 44. .40 7

ATOM 747 CA SER A 93 42. .076 32, ,483 35. ,687 1. .00 41. .89 6

ATOM 748 CB SER A 93 43, ,248 33, .080 36, .445 1, .00 40, .83 6

ATOM 74-9 OG SER A 93 44, .400 32, .275 36, .274 1, .00 37, .97 8

ATOM 750 C SER A 93 42. .541 32. .112 34. .295 1. .00 42. .18 6

ATOM 751 O SER A 93 42. .762 30. ,942 34, .023 1. .00 41. .06 8

ATOM 752 N LYS A 94 42, .693 33, .081 33, .401 1, .00 43 .27 7

ATOM 753 CA LYS A 94 43, .178 32, .712 32, .077 1, .00 45, .47 6

ATOM 754 CB LYS A 94 42, .703 33, .680 30, .988 1. . 00 44. .26 6

ATOM 755 CG LYS A 94 42, .747 35. .142 31, .314 1. .00 44, .49 6

ATOM 756 CD LYS A 94 41, .907 35. .918 30, .309 1. .00 46. .66 6

ATOM 757 CE LYS A 94 42 .209 35 .470 28 .885 1, .00 47. .75 6

ATOM 758 NZ LYS A 94 41, .443 36, .237 27, .873 1. .00 49, .19 7

ATOM 759 C LYS A 94 44, .688 32, .592 32, .089 1, .00 43. .67 6

ATOM 760 O LYS A 94 45 .359 33, .102 32, .980 1, .00 44, .46 8

ATOM 761 N PRO A 95 45 .243 31. .889 31. .105 1, .00 43 .23 7

ATOM 762 CD PRO A 95 44 .559 31 .199 30 .004 1, .00 41 .03 6

ATOM 763 CA PRO A 95 46 .692 31. .695 31 .024 1, .00 42 .80 6

ATOM 764 CB PRO A 95 46 .858 30 .719 29 .862 1, .00 43 .77 6

ATOM 765 CG PRO A 95 45 .515 30 .078 29 .725 1 .00 43 .00 6

ATOM 766 C PRO A 95 47 .480 32 .962 30 .783 1 .00 41 .84 6

ATOM 767 0 PRO A 95 47 .178 33 .729 29 .861 1 .00 41 .82 8

ATOM 768 N GLU A 96- 48 .483 33 .183 31 .627 1 .00 40 .74 7

ATOM 769 CA GLU A 96 49 .350 34 .322 31 .472 1 .00 39 .25 6

ATOM 770 CB GLU A 96 49 .704 34 .960 32 .817 1 .00 41 .50 6

ATOM 771 CG GLU A 96 50 .548 36 .235 32 .682 1 .00 46 .46 6

ATOM 772 CD GLU A 96 50 .864 36 .910 34 .014 1 .00 51 .10 6

ATOM 773 OE1 GLU A 96 50 .172 36 .591 35 .002 1 .00 55 .39 8

ATOM 774 OE2 GLU A 96 51 .784 37 .772 34 .079 1 .00 51 .01 8

ATOM 775 C GLU A 96 50 .583 33 .713 30 .851 1 .00 38 .30 6

ATOM 776 0 GLU A 96 51 .424 33 .169 31 .548 1 .00 37 .33 8

ATOM 777 N VAL A 97 50 .662 33 .770 29 .528 1 .00 36 .80 7

ATOM 778 CA VAL A 97 51 .813 33 .231 28 .821 1 .00 37 .13 6

ATOM 779 CB VAL A 97 51 .514 33 .092 27 .313 1 .00 35 . 99 6

ATOM 780 CGI VAL A 97 52 .704 32 .480 26 .600 1 .00 34 .96 6

ATOM 781 CG2 VAL A 97 50 .287 32 .222 27 .122 1 .00 30 .36 6

ATOM 782 C VAL A 97 53 .002 34 .160 29 .061 1 .00 37 .37 6 On 01 4^ ω l\3 l\5 o π o en o Cn o en o en en

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ATOM 844 C VAL A 105 59.,731 22.355 12.799 1.00 49.71 6

ATOM 845 O VAL A 105 60. 688 22. 946 12. 283 1. 00 48. 12 8

ATOM 846 N VAL A 106 59. 597 21. 030 12. 821 1. 00 50. ,55 7

ATOM 847 CA VAL A 106 60. ,571 20. ,123 12. 232 1. 00 51. .43 6

ATOM 848 CB VAL A 106 60. 648 18. 816 13. 037 1. 00 52. 44 6

ATOM 849 CGI VAL A 106 61. ,828 17. .987 12. ,571 1. 00 50. ,24 6

ATOM 850 CG2 VAL A 106 60. 762 19. 128 14. 521 1. 00 52. 53 6

ATOM 851 C VAL A 106 60. ,142 19. ,809 10. ,805 1. 00 52. ,38 6

ATOM 852 O VAL A 106 58. ,961 19. ,644 10. 536 1. 00 52. ,65 8

ATOM 853 N SER A 107 61. ,101 19. ,718 9. ,895 1. 00 52. .34 7

ATOM 854 CA SER A 107 60. .803 19. ,447 8. ,492 1. 00 54. ,32 6

ATOM 855 CB SER A 107 62. .111 19. ,185 7. ,735 1. 00 55. ,62 6

ATOM 856 OG SER A 107 62. ,965 18. ,316 8. ,462 1. 00 60. ,14 8

ATOM 857 C SER A 107 59. .795 18. ,328 8. ,186 1. 00 53. .69 6

ATOM 858 O SER A 107 59. .191 18. ,304 7. ,111 1. 00 51. ,90 8

ATOM 859 N ASP A 108 59. .598 17. ,412 9. ,122 1. 00 54. ,61 7

ATOM 860 CA ASP A 108 58, .667 16, .318 8, .890 1. ,00 57, .15 6

ATOM 861 CB ASP A 108 59. .164 15. ,046 9. ,580 1. 00 58. .72 6

ATOM 862 CG ASP A 108 59. .114 15. .134 11. ,097 1. 00 61. ,68 6

ATOM 863 ODl ASP A 108 59. .391 16. ,221 11, .642 1. ,00 64. .28 8

ATOM 864 OD2 ASP A 108 58. .816 14, ,105 11, ,747 1. 00 62. .23 8

ATOM 865 C ASP A 108 57. .235 16, .615 9, .320 1. ,00 58. .57 6

ATOM 866 O ASP A 108 56. .379 15, .725 9. ,301 1. 00 58. .30 8

ATOM 867 N GLY A 109 56. .979 17 .865 9, .703 1. .00 59, .14 7

ATOM 868 CA GLY A 109 55 .649 18 .271 10, .116 1. .00 58, .25 6

ATOM 869 C GLY A 109 55. .397 18, .166 11. .602 1. 00 58. .69 6

ATOM 870 O GLY A 109 54 .273 18, .374 12. ,054 1. ,00 59. ,98 8

ATOM 871 N GLU A 110 56 .423 17 .821 12, .369 1. .00 58 .71 7

ATOM 872 CA GLU A 110 56 .255 17, .713 13, .813 1. ,00 58, .33 6

ATOM 873 CB GLU A 110 57. .380 16, .871 14, .425 1, ,00 61, .59 6

ATOM 874 CG GLU A 110 57 .062 16. .242 15, .797 1. ,00 66, .10 6

ATOM 875 CD GLU A 110 55 .913 15. .218 15, .728 1. .00 70, .89 6

ATOM 876 OΞ1 GLU A 110 55 .634 14 .710 14, .600 1, ,00 70. .53 8

ATOM 877 OE2 GLU A 110 55 .303 14, .916 16, ,800 1, ,00 70. .77 8

ATOM 878 C GLU A 110 56 .293 19 .136 14 .369 1. .00 56, .59 6

ATOM 879 O GLU A 110 57 .114 19 .955 13 .941 1, .00 54 .81 8

ATOM 880 N VAL A 111 55 .392 19 .425 15, .307 1. ,00 54, .27 7

ATOM 881 CA VAL A 111 55 .310 20 .745 15 .912 1 .00 52 .01 6

ATOM 882 CB VAL A 111 53 .949 21 .412 15 .616 1. .00 50 .79 6

ATOM 883 CGI VAL A 111 53 .902 22 .795 16, .242 1. ,00 47 .90 6

ATOM 884 CG2 VAL A 111 53 .718 21 .489 14 .115 1, .00 50 .80 6

ATOM 885 C VAL A 111 55 .465 20 . 666 17 .418 1, ,00 51 .33 6

ATOM 886 O VAL A 111 54 .833 19 .830 18 .057 1 .00 50 .54 8

ATOM 887 N LEU A 112 56 .300 21 .539 17 .979 1, .00 49 .64 7

ATOM 888 CA LEU A 112 56 .501 21 .569 19 .418 1 .00 50 .36 6

ATOM 889 CB LEU A 112 57 .911 21 .107 19 .791 1 .00 54 .86 6

ATOM 890 CG LEU A 112 58 .651 20 .020 18 .989 1, ,00 59 .01 6

ATOM 891 CDl LEU A 112 57 .699 18 .865 18 .631 1, .00 60 .90 6

ATOM 892 CD2 LEU A 112 59 .248 20 .632 17 .727 1 .00 57 .28 6

ATOM 893 C LEU A 112 56 .297 22 .980 19 .946 1 .00 49 .94 6

ATOM 894 O LEU A 112 57 .004 23 .893 19 .553 1 .00 49 .38 8

ATOM 895 N TYR A 113 55 .323 23 .151 20 .833 1 .00 49 .46 7

ATOM 896 CA TYR A 113 55 .036 24 .446 21 .437 1 .00 47 .23 6

ATOM 897 CB TYR A 113 53 .643 24 .939 21 .021 1 .00 45 .72 6

ATOM 898 CG TYR A 113 53 .222 26 .279 21 .621 1 .00 46 .02 6

ATOM 899 CDl TYR A 113 54 .092 27 .364 21 .654 1 .00 42 .86 6

ATOM 900 CEl TYR A 113 53 .691 28 .588 22 .179 1 .00 43 .03 6

ATOM 901 CD2 TYR A 113 51 .936 26 .462 22 .131 1 .00 45 .25 6

ATOM 902 CE2 TYR A 113 51 .533 27 .682 22 .653 1 .00 41 .00 6

ATOM 903 CZ TYR A 113 52 .410 28 .740 22 .677 1 .00 42 .42 6

ATOM 904 OH TYR A 113 52 .008 29 .952 23 .211 1 .00 42 .79 8 ATOM 905 C TYR A 113 55.097 24.,250 22.936 1.00 47.38 6

ATOM 906 O TYR A 113 54. 304 23. ,508 23. 506 1. 00 47. 08 8

ATOM 907 N MET A 114 56. ,047 24. .916 23. ,577 1. ,00 48. ,38 7

ATOM 908 CA MET A 114 56. 205 24. ,788 25. 015 1. 00 48. 39 6

ATOM 909 CB MET A 114 57. 485 24. ,020 25. ,304 1. 00 52. .09 6

ATOM 910 CG MET A 114 57. 675 23. ,679 26. ,739 1. 00 59. ,10 6

ATOM 911 SD MET A 114 59. 383 23. ,282 26. ,925 1. 00 67. ,20 16

ATOM 912 CE MET A 114 59. ,324 21. ,518 26. ,416 1. 00 67. ,26 6

ATOM 913 C MET A 114 56. 245 26. ,148 25. ,701 1. 00 46. ,12 6

ATOM 914 O MET A 114 57. ,308 26. .660 26. ,027 1. ,00 46. .76 8

ATOM 915 N PRO A 115 55. ,076 26. .754 25. ,922 1. 00 44. 80 7

ATOM 916 CD PRO A 115 53. ,740 26. .329 25, ,463 1. ,00 44. ,54 6

ATOM 917 CA PRO A 115 55. ,005 28. .059 26. ,575 1. ,00 44. .08 6

ATOM 918 CB PRO A 115 53. ,675 28. .598 26, ,075 1. ,00 45. ,01 6

ATOM 919 CG PRO A 115 52. .831 27, ,366 26, .077 1, ,00 43. ,44 6

ATOM 920 C PRO A 115 55. ,030 27. ,935 28. ,102 1. 00 43. ,24 6

ATOM 921 O PRO A 115 54. ,552 26, .947 28. .664 1. ,00 40. .79 8

ATOM 922 N SER A 116 55, .599 28, .929 28. ,771 1. ,00 42. ,36 7

ATOM 923 CA SER A 116 55, .627 28 .911 30, .227 1. .00 42. .64 6

ATOM 924 CB SER A 116 56. ,851 29. ,624 30. .764 1. ,00 40, .99 6

ATOM 925 OG SER A 116 56, ,852 29. .573 32. ,169 1. ,00 41. ,56 8

ATOM 926 C SER A 116 54. .382 29, .658 30. .653 1. ,00 42. .71 6

ATOM 927 O SER A 116 54. ,184 30. .809 30. ,266 1. ,00 44. ,52 8

ATOM 928 N ILE A 117 53. .545 29, .006 31. ,446 1. ,00 41. .18 7

ATOM 929 CA ILE A 117 52. ,303 29, .616 31, ,879 1. ,00 40. .12 6

ATOM 930 CB ILE A 117 51, .104 28 .814 31, .325 1. .00 37, .67 6

ATOM 931 CG2 ILE A 117 49. .805 29, ,400 31. ,819 1. ,00 38. ,25 6

ATOM 932 CGI ILE A 117 51. ,134 28, .825 29. ,798 1. ,00 36, .76 6

ATOM 933 CDl ILE A 117 50, .212 27, .822 29. ,169 1. ,00 33. .48 6

ATOM 934 C ILE A 117 52. .114 29, .768 33. .388 1. ,00 41. .31 6

ATOM 935 O ILE A 117 52. .444 28, .876 34. .168 1. ,00 43. .78 8

ATOM 936 N ARG A 118 51. .607 30, .925 33. .795 1. ,00 41. .35 7

ATOM 937 CA ARG A 118 51, .283 31 .153 35, .194 1. .00 41, .26 6

ATOM 938 CB ARG A 118 51. .789 32, .496 35, .709 1. ,00 38. .56 6

ATOM 939 CG ARG A 118 51. .290 32, .758 37. ,113 1. . 00 37. .29 6

ATOM 940 CD ARG A 118 52. .006 33. .883 37, ,817 1. .00 38. .24 6

ATOM 941 NE ARG A 118 51. .453 34, .066 39, .150 1. .00 41. .49 7

ATOM 942 CZ ARG A 118 52. .006 34, .794 40, .107 1, ,00 43. .10 6

ATOM 943 NHl ARG A 118 53, .148 35, .423 39, .892 1. .00 46, .98 7

ATOM 944 NH2 ARG A 118 51 .417 34 .890 41 .282 1, .00 43 .21 7

ATOM 945 C ARG A 118 49 .765 31 .156 35 .179 1, .00 41, .21 6

ATOM 946 O ARG A 118 49, .144 31 .842 34 .374 1, .00 41, .57 8

ATOM 947 N GLN A 119 49 .152 30 .394 36 .063 1, .00 41, .94 7

ATOM 948 CA GLN A 119 47 .702 30 .329 36 .056 1, .00 43 .44 6

ATOM 949 CB GLN A 119 47 .292 29 .433 34 .895 1 .00 41 .21 6

ATOM 950 CG GLN A 119 45 .825 29 .257 34 .672 1 .00 43 .47 6

ATOM 951 CD GLN. A 119 45 .552 28 .554 33 .364 1 .00 41 .25 6

ATOM 952 OΞ1 GLN A 119 46 .333 27 .721 32 .931 1 .00 42 .28 8

ATOM 953 NE2 GLN A 119 44 .439 28 .877 32 .736 1 .00 42 .81 7

ATOM 954 C GLN A 119 47 .183 29 .801 37 .385 1 .00 44 .09 6

ATOM 955 O GLN A 119 47 .866 29 .041 38 .062 1 .00 43 .59 8

ATOM 956 N ARG A 120 45 .990 30 .228 37 .778 1 .00 46 .26 7

ATOM 957 CA ARG A 120 45 .433 29 .762 39 .036 1 .00 48 .60 6

ATOM 958 CB ARG A 120 44 .780 30 .900 39 .797 1 .00 51 .27 6

ATOM 959 CG ARG A 120 45 .705 32 .036 40 .096 1 .00 60 .62 6

ATOM 960 CD ARG A 120 45 .261 32 .728 41 .362 1 .00 67 .20 6

ATOM 961 NE ARG A 120 45 .730 32 .045 42 .575 1 .00 69 .70 7

ATOM 962 CZ ARG A 120 44 .989 31 .859 43 .668 1 .00 69 .76 6

ATOM 963 NHl ARG A 120 43 .728 32 .279 43 .709 1 .00 68 .36 7

ATOM 964 NH2 ARG A 120 45 .533 31 .307 44 .748 1 .00 70 .33 7

ATOM 965 C ARG A 120 44 .414 28 .669 38 .804 1 .00 48 .02 6 ATOM 966 0 ARG A 120 43.706 28.669 37.788 1.00 46.40 8

ATOM 967 N PHE A 121 44. 341 27. 739 39. 753 1. 00 46. ,74 7

ATOM 968 CA PHE A 121 43. 406 26. .628 39. 648 1. 00 48. ,15 6

ATOM 969 CB PHE A 121 44. 129 25. 330 39. 301 1. 00 45. ,72 6

ATOM 970 CG PHE A 121 44. 973 25. ,415 38. 074 1. 00 44. 95 6

ATOM 971 CDl PHE A 121 46. 240 25. 993 38. 122 1. 00 43. ,54 ^•6

ATOM 972 CD2 PHE A 121 44. 495 24. ,944 36. 866 1. 00 41. .66 6

ATOM 973 CE1 PHE A 121 47. 011 26. ,099 36. ,986 1. 00 42, .05 6

ATOM 974 CE2 PHE A 121 45. 257 25. ,047 35. ,733 1. 00 41, ,56 6

ATOM 975 CZ PHE A 121 46. ,521 25, .628 35. ,790 1. 00 42. .24 6

ATOM 976 C PHE A 121 42. ,622 26. ,376 40. ,908 1. 00 49, .43 6

ATOM 977 O PHE A 121 42. 996 26. ,810 42. ,001 1. oo ^' 49, ,47 8

ATOM 978 N SER A 122 41. .524 25. .653 40. ,727 1. 00 51, .17 7

ATOM 979 CA SER A 122 40. ,657 25. ,250 41. 823 1. 00 52, .06 6

ATOM 980 CB SER A 122 39. ,193 25. .501 41. .477 1. 00 52, .69 6

ATOM 981 OG SER A 122 38. ,354 25. ,046 42. ,520 .1. 00 51, .12 8

ATOM 982 C SER A 122 40, .896 23, .754 41. .978 1. ,00 52. .70 6

ATOM 983 O SER A 122 40, .529 22, .966 41. .103 1. ,00 51. .13 8

ATOM 984 N CYS A 123 41. ,543 23, .369 43, .070 1. 00 52, .97 7

ATOM 985 CA CYS A 123 41. .820 21 .967 43, .312 1. ,00 56 .03 6^'

ATOM 986 C CYS A 123 42. .017 21, .693 44. ,803 1. ,00 59, .48 6

ATOM 987 O CYS A 123 41, .882 22, .602 45. .634 1. ,00 60, .13 8

ATOM 988 CB CYS A 123 43, .052 21, .555 42, .534 1. .00 53 .78 6

ATOM 989 SG CYS A 123 44, .483 22, .558 42, ,968 1. ,00 56, .89 16

ATOM 990 N ASP A 124 42, .342 20, .443 45, .143 1. ,00 61, .91 7

ATOM 991 CA ASP A 124 42. .525 20. .084 46. .542 1. ,00 63. .81 6

ATOM 992 CB ASP A 124 42. .391 18, .571 46, .749 1, .00 65 .05 6

ATOM 993 CG ASP A 124 41 .828 18 .226 48 .128 1, .00 66 .74 6

ATOM 994 ODl ASP A 124 42 .113 18 .973 49, .103 1, ,00 65 .03 8

ATOM 995 OD2 ASP A 124 41 .101 17 .209 48, .234 1. ,00 67 .39 8

ATOM 996 C ASP A 124 43 .857 20 .543 47 .110 1, .00 63 .72 6

ATOM 997 O ASP A 124 44 .910 20 .036 46, .745 1. ,00 64 .11 8

ATOM 998 N VAL A 125 43 .794 21, .495 48, .031 1. .00 64 .49 7

ATOM 999 CA VAL A 125 44 .981 22 .042 48, .681 1. ,00 63 .28 6

ATOM 1000 CB VAL A 125 44 .861 23 .578 48, .804 1. ,00 62 .29 6

ATOM 1001 CGI VAL A 125 46 .058 24 .135 49, .539 1. ,00 61 .76 6

ATOM 1002 CG2 VAL A 125 44 .735 24, .194 47, .429 1. .00 61 .51 6

ATOM 1003 C VAL A 125 45 .190 21 .449 50 .078 1. .00 63 .42 6

ATOM 1004 O VAL A 125 46 .283 21 .534 50 .632 1, .00 63 .08 8

ATOM 1005 N SER A 126 44 .141 20 .848 50, .641 1, .00 64 .34 7

ATOM 1006 CA SER A 126 44 .218 20 .252 51 .981 1, .00 64 .43 6

ATOM 1007 CB SER A 126 42 .924 19 .503 52, .302 1, .00 63 .15 6

ATOM 1008 OG SER A 126 42 .723 18 .465 51 .371 1, .00 58 .95 8

ATOM 1009 C SER A 126 45 .414 19 .306 52 .128 1 .00 64 .40 6

ATOM 1010 O SER A 126 45 .636 18 .420 51 .299 1 .00 62 .89 8

ATOM 1011 N GLY A 127 46 .188 19 .510 53 .186 1, .00 65 .00 7

ATOM 1012 CA GLY A 127 47 .343 18 .676 53. .416 1, .00 67 .55 6

ATOM 1013 C GLY A 127 48 .647 19 .293 52 .939 1 .00 71 .25 6

ATOM 1014 O GLY A 127 49 .725 18 .717 53 .130 1 .00 72 .65 8

ATOM 1015 N VAL A 128 48 .572 20 .463 52 .317 1 .00 72 .58 7

ATOM 1016 CA VAL A 128 49 .779 21 .109 51 .830 1 .00 73 .82 6

ATOM 1017 CB VAL A 128 49 .505 22 .482 51 .162 1 .00 73 .07 6

ATOM 1018 CGI VAL A 128 48 .855 22 .272 49 .837 1 .00 75 .57 6

ATOM 1019 CG2 VAL A 128 48 .625 23 .359 52 .065 1 .00 72 .32 6

ATOM 1020 C VAL A 128 50 .792 21 .376 52 .912 1 .00 75 .60 6

ATOM 1021 O VAL A 128 51 .984 21 .102 52 .727 1 .00 76 .00 8

ATOM 1022 N ASP A 129 50 .324 21 .907 54 .041 1 .00 77 .55 7

ATOM 1023 CA ASP A 129 51 .241 22 .287 55 .107 1 .00 79 .65 6

ATOM 1024 CB ASP A 129 50 .507 23 .015 56 .235 1 .00 79 .08 6

ATOM 1025 CG ASP A 129 51 .427 23 .954 57 .017 1 .00 80 .06 6

ATOM 1026 ODl ASP A 129 51 .000 25 .097 57 .338 1 .00 80 .12 8 ATOM 1027 OD2 ASP A 129 52.578 23.546 57.311 1.00 80.59 8

ATOM 1028 C ASP A 129 52. 085 21. 164 55. 676 1. 00 80. 77 6

ATOM 1029 O ASP A 129 53. 089 21. 441 56. ,355 1. 00 80. 25 8

ATOM 1030 N THR A 130 51. 724 19. 907 55. ,389 1. 00 80. 58 7

ATOM 1031 CA THR A 130 52. 541 18. 824 55. ,925 1. 00 81. 44 6

ATOM 1032 CB THR A 130 52. 508 18. 858 57. ,465 1. 00 83. 89 6

ATOM 1033 OG1 THR A 130 51. 433 19. 722 57. ,880 1. 00 85. 49 8

ATOM 1034 CG2 THR A 130 53. .882 19. ,331 58. .047 1. .00 83. ,12 6

ATOM 1035 C THR A 130 52. ,309 17. ,374 55. ,529 1. ,00 80. ,12 6

ATOM 1036 O THR A 130 51. ,199 16. ,974 55. .148 1. ,00 78. 43 8

ATOM 1037 N GLU A 131 53. ,404 16. ,611 55. ,654 1. ,00 79. 90 7

ATOM 1038 CA GLU A 131 53. 459 15. 165 55. ,432 1. 00 80. 19 6

ATOM 1039 CB GLU A 131 52. ,364 14. ,489 56. .272 1. ,00 82. ,93 6

ATOM 1040 CG GLU A 131 52, ,693 14. .372 57. .760 1, ,00 86. ,59 6

ATOM 1041 CD GLU A 131 51. .440 14. .289 58, .632 1. ,00 88. ,67 6

ATOM 1042 OE1 GLU A 131 50. .524 13. .470 58, .311 1. .00 89. ,43 8

ATOM 1043 OE2 GLU A 131 51. .380 15. .050 59, ,638 1. .00 88. ,79 8

ATOM 1044 C GLU A 131 53. .378 14, .637 54, .012 1. .00 79, ,05 6

ATOM 1045 O GLU A 131 54. ,337 14. ,716 53. .231 1. ,00 77. ,86 8

ATOM 1046 N SER A 132 52. ,227 14. ,033 53. .727 1, ,00 77. ,68 7

ATOM 1047 CA SER A 132 51. .915 13. ,474 52. .426 1, ,00 76. ,46 6

ATOM 1048 CB SER A 132 50. ,796 12, ,429 52. .576 1, ,00 76. ,05 6

ATOM 1049 OG SER A 132 49. ,642 12. .990 53. .176 1, ,00 74. ,46 8

ATOM 1050 C SER A 132 51. ,462 14. .653 51, ,533 1. ,00 75, ,70 6

ATOM 1051 O SER A 132 51, .123 14, ,479 50, .355 1. .00 75. ,58 8

ATOM 1052 N GLY A 133 51, .468 15. .848 52, .127 1. .00 73. .94 7

ATOM 1053 CA GLY A 133 51, .094 17. .056 51, .421 1. .00 71. .52 6

ATOM 1054 C GLY A 133 49, .754 16. .971 50, .735 1. .00 70. .11 6

ATOM 1055 O GLY A 133 48 .927 16 .115 51 .060 1 .00 69, .95 8

ATOM 1056 N ALA A 134 49, .540 17, .864 49 .774 1, .00 68. .35 7

ATOM 1057 CA ALA A 134 48 .290 17, .895 49 .033 1, .00 65, .73 6

ATOM 1058 CB ALA A 134 47 .748 19, .321 48 .982 1, .00 65, ,87 6

ATOM 1059 C ALA A 134 48. .476 17. .359 47. .621 1. .00 63. .96 6

ATOM 1060 O ALA A 134 49 .600 17, .219 47 .124 1 .00 61, .93 8

ATOM 1061 N THR A 135 47 .353 17 .048 46 .985 1 .00 63 .38 7

ATOM 1062 CA THR A 135 47 .359 16 .549 45 .621 1 .00 62 .44 6

ATOM 1063 CB THR A 135 47 .003 15 .066 45 .562 1 .00 62, .52 6

ATOM 1064 OG1 THR A 135 47 .951 1 .323 46 .345 1 .00 62 .25 8

ATOM 1065 CG2 THR A 135 47 .040 14 .574 44 .122 1 .00 61 .31 6

ATOM 1066 C THR A 135 46 .350 17, .355 44 .820 1, .00 61, .68 6

ATOM 1067 O THR A 135 45 .120 17, .188 44 .944 1, .00 60, .36 8

ATOM 1068 N CYS A 136 46 .900 18, .259 44 .017 1, .00 59. .30 7

ATOM 1069 CA CYS A 136 46 .115 19 .129 43 .178 1 .00 56, .11 6

ATOM 1070 C CYS A 136 46 .111 18 .538 41 .778 1 .00 55, .58 6

ATOM 1071 0 CYS A 136 47 .168 18, .370 41 .163 1 .00 53 .10 8

ATOM 1072 CB CYS A 136 46 .739 20 .518 43 .181 1 .00 55 .44 6

ATOM 1073 SG CYS A 136 46 .010 21 .663 41 .978 1 .00 54 .51 16

ATOM 1074 N ARG A 137 44 .917 18 .191 41 .298 1 .00 55 .48 7

ATOM 1075 CA ARG A 137 44 .764 17 .611 39 .968 1 .00 56 .07 6

ATOM 1076 CB ARG A 137 43 .786 16 .431 39 .990 1 .00 58 .27 6

ATOM 1077 CG ARG A 137 44 .213 15 .318 40 .915 1 .00 62 .94 6

ATOM 1078 CD ARG A 137 43 .017 14 .517 41 .384 1 .00 67 .01 6

ATOM 1079 NE ARG A 137 43 .308 13 .821 42 .641 1 .00 72 .70 7

ATOM 1080 CZ ARG A 137 44 .131 12 .772 42 .762 1 .00 74 .69 6

ATOM 1081 NHl ARG A 137 44 .765 12 .270 41 .696 1 .00 74 .12 7

ATOM 1082 NH2 ARG A 137 44 .326 12 .226 43 .958 1 .00 74 .27 7

ATOM 1083 C ARG A 137 44 .265 18 .670 39 .010 1 .00 53 .72 6

ATOM 1084 O ARG A 137 43 .325 19 .396 39 .301 1 .00 51 .52 8

ATOM 1085 N ILE A 138 44 .917 18 .738 37 .860 1 .00 52 .05 7

ATOM 1086 CA ILE A 138 44 .582 19 .696 36 .825 1 .00 50 .25 6

ATOM 1087 CB ILE A 138 45 .778 20 .624 36 .557 1 .00 49 .78 6 ATOM 1088 CG2 ILE A 138 45.449 21.,566 35.,421 1.00 48.,31 6

ATOM 1089 CGI ILE A 138 46. ,150 21. ,389 37. ,837 1. ,00 48. ,07 6

ATOM 1090 CDl ILE A 138 47, .444 22, .144 37. .750 1. .00 41, .58 6

ATOM 1091 C ILE A 138 44. .270 18. ,925 35. ,555 1. ,00 49, ,76 6

ATOM 1092 O ILE A 138 45. ,119 18. ,190 35. ,058 1. 00 50. ,40 8

ATOM 1093 N LYS A 139 43. .059 19. ,081 35. .032 1. ,00 49. ,44 7

ATOM 1094 CA LYS A 139 42. .672 18. .374 33. .809 1. ,00 51. .81 6

ATOM 1095 CB LYS A 139 41. .285 17. .713 33, ,969 1. .00 52. .86 6

ATOM 1096 CG LYS A 139 41. ,176 16. .772 35. .164 1. ,00 56. ,41 6

ATOM 1097 CD LYS A 139 39. .919 15, .940 35. .137 1. .00 57. .01 6

ATOM 1098 CE LYS A 139 39. .978 14. .888 34. .047 1. .00 60. .31 6

ATOM 1099 NZ LYS A 139 38. .728 14, ,066 33, ,965 1. .00 59. .02 7

ATOM 1100 C LYS A 139 42. .628 19, .317 32, .615 1. .00 51, .20 6

ATOM 1101 O LYS A 139 41, .964 20, .340 32, .673 1. .00 51. ,87 8

ATOM 1102 N ILE A 140 43. .325 18, ,979 31. ,535 1. ,00 49, .23 7

ATOM 1103 CA ILE A 140 43. .295 19. .826 30. .354 1. ,00 49. .38 6

ATOM 1104 CB ILE A 140 44 .578 20 .710 30, .278 1, .00 50 .36 6

ATOM 1105 CG2 ILE A 140 44. .889 21. .277 31, ,653 1. ,00 51. ,45 6

ATOM 1106 CGI ILE A 140 45. .794 19. ,900 29. .868 1. ,00 50, ,82 6

ATOM 1107 CDl ILE A 140 47 .103 20, .630 30, .148 1. .00 51, .49 6

ATOM 1108 C ILE A 140 43. .088 19. ,025 29. ,066 1. ,00 47, ,91 6

ATOM 1109 O ILE A 140 43 .721 18. .006 28, .859 1, .00 46 .67 8

ATOM 1110 N GLY A 141 42, .168 19, .485 28, .220 1. ,00 48, .53 7

ATOM llll CA GLY A 141 41 .885 18, .811 26, .959 1. .00 47, .60 6

ATOM 1112 C GLY A 141 41, .255 19, .765 25. .958 1. .00 48. .49 6

ATOM 1113 O GLY A 141 40. .938 20. ,900 26. .317 1. ,00 49, ,03 8

ATOM 1114 N SER A 142 41. .070 19, .329 24, .712 1, .00 46, .01 7

ATOM 1115 CA SER A 142 40, .466 20. ,195 23. .699 1. .00 43, ,95 6

ATOM 1116 CB SER A 142 40. .306 19. .466 22, .370 1. .00 44, ,36 6

ATOM 1117 OG SER A 142 39, .494 20, .214 21, .477 1. ,00 39, .73 8

ATOM 1118 C SER A 142 39 .107 20, .686 24, .144 1, .00 45, .09 6

ATOM 1119 O SER A 142 38, .319 19, .934 24. .714 1. .00 47, ,13 8

ATOM 1120 N TRP A 143 38 .822 21, .947 23. .862 1. .00 43, .97 7

ATOM 1121 CA TRP A 143 37 .564 22 .537 24, .256 1, .00 41, .28 6

ATOM 1122 CB TRP A 143 37, .754 24, ,033 24. .473 1. .00 42, .28 6

ATOM 1123 CG TRP A 143 36 .577 24, .697 25, .126 1. .00 42, .52 6

ATOM 1124 CD2 TRP A 143 36, .215 24, ,610 26, ,505 1. .00 39, .43 6

ATOM 1125 CE2 TRP A 143 35 .025 25, .359 26, ,676 1. .00 39, .15 6

ATOM 1126 CE3 TRP A 143 36 .778 23 .969 27 .613 1 .00 37 .16 6

ATOM 1127 CDl TRP A 143 35 .618 25, .480 24, .526 1, .00 41, .93 6

ATOM 1128 NEl TRP A 143 3 .681 25, .880 25, .456 1, .00 40, .50 7

ATOM 1129 CZ2 TRP A 143 34 .393 25 .480 27 .911 1 .00 39 .06 6

ATOM 1130 CZ3 TRP A 143 36 .150 24 .090 28 .837 1 .00 39 .37 6

ATOM 1131 CH2 TRP A 143 34 .968 24 .840 28, .978 1 .00 39, .40 6

ATOM 1132 C TRP A 143 36 .450 22 .307 23 .258 1 .00 41 .37 6

ATOM 1133 O TRP A 143 35 .287 22, .239 23, .632 1, .00 42, .45 8

ATOM 1134 N THR A 144 36 .790 22 .179 21 .983 1 .00 41 .97 7

ATOM 1135 CA THR A 144 35 .760 21 .992 20 .979 1 .00 41 .13 6

ATOM 1136 CB THR A 144 35 .703 23 .191 20, .051 1 .00 39 .00 6

ATOM 1137 OG1 THR A 144 36 .994 23 .416 19 .490 1 .00 39 .19 8

ATOM 1138 CG2 THR A 144 35 .288 24 .420 20 .818 1 .00 37 .78 6

ATOM 1139 C THR A 144 35 .879 20 .738 20 .148 1 .00 42 .54 6

ATOM 1140 O THR A 144 34 .941 20 .385 19 .443 1 .00 45 .82 8

ATOM 1141 N HIS A 145 37 .012 20 .054 20, .233 1, .00 43, .18 7

ATOM 1142 CA HIS A 145 37 .187 18 .837 19 .459 1 .00 46 .20 6

ATOM 1143 CB HIS A 145 38 .517 18 .875 18 .707 1 .00 46 .05 6

ATOM 1144 CG HIS A 145 38 .588 19 .933 17 .646 1 .00 46 .56 6

ATOM 1145 CD2 HIS A 145 37 .994 20 .022 16 .432 1 .00 45 .44 6

ATOM 1146 NDl HIS A 145 39 .366 21 .061 17 .772 1 .00 44 .61 7

ATOM 1147 CEl HIS A 145 39 .250 21 .797 16 .682 1 .00 43 .87 6

ATOM 1148 NE2 HIS A 145 38 .423 21 .189 15 .853 1 .00 41 .35 7 ATOM 1149 C HIS A 145 37.105 17.570 20.303 1.00 47.36 6

ATOM 1150 O HIS A 145 37. 811 17. 422 21. 298 1. 00 47. 71 8

ATOM 1151 N HIS A 146 36. 230 16. 656 19. 898 1. ,00 48. 75 7

ATOM 1152 CA HIS A 146 36. 067 15. 400 20. 609 1. 00 50. 47 6

ATOM 1153 CB HIS A 146 34. 658 14. 846 20. 365 1. 00 49. 28 6

ATOM 1154 CG HIS A 146 34. 314 14. 694 18. 919 1. 00 50. 42 6

ATOM 1155 CD2 HIS A 146 34. 954 14. 057 17. 910 1. 00 50. 68 6

ATOM 1156 NDl HIS A 146 33. 183 15. 248 18. 362 1. 00 51. 90 7

ATOM 1157 CEl HIS A 146 33. 138 14. ,962 17. 073 1. 00 49. 57 6

ATOM 1158 NE2 HIS A 146 34. 202 14. ,239 16. ,774 1. ,00 51. ,03 7

ATOM 1159 C HIS A 146 37. 137 14. 396 20. 167 1. 00 49. 74 6

ATOM 1160 O HIS A 146 37. 927 14. 673 19. 268 1. ,00 49. ,87 8

ATOM 1161 N SER A 147 37. 145 13. ,234 20. ,809 1. ,00 50. ,23 7

ATOM 1162 CA SER A 147 38. 101 12. 158 20. 543 1. ,00 50. 98 6

ATOM 1163 CB SER A 147 37. 722 10. ,934 21. ,372 1. ,00 50. ,73 6

ATOM 1164 OG SER A 147 36. ,346 10. ,642 21. ,240 1. ,00 51. ,84 8

ATOM 1165 C SER A 147 38. ,314 11. .730 19. ,096 1, ,00 51. ,53 6

ATOM 1166 O SER A 147 39. ,374 11. ,228 18. 754 1. ,00 50. ,53 8

ATOM 1167 N ARG A 148 37. ,319 11, .925 18. ,245 1, ,00 53. ,75 7

ATOM 1168 CA ARG A 148 37. .444 11. .528 16, ,850 1, ,00 56, ,68 6

ATOM 1169 CB ARG A 148 36. ,052 11. ,408 16. ,221 1. ,00 60 . ,77 6

ATOM 1170 CG ARG A 148 35. .100 10. .487 16. .985 1, ,00 70. .28 6

ATOM 1171 CD ARG A 148 33. .673 10, .516 16, .423 1, .00 76, ,18 6

ATOM 1172 NE ARG A 148 32. .702 9. .919 17. .351 1. .00 83. ,11 7

ATOM 1173 CZ ARG A 148 32. .685 8, .632 17, .719 1. .00 85. .65 6

ATOM 1174 NHl ARG A 148 33. .595 7. .781 17. .243 1. .00 86. .70 7

ATOM 1175 NH2 ARG A 148 31. .746 8. .187 18. .549 1. .00 85. .60 7

ATOM 1176 C ARG A 148 38. .295 12. ,502 16. .025 1. .00 56. ,73 6

ATOM 1177 O ARG A 148 38, .774 12, .157 14, ,938 1, .00 56, .48 8

ATOM 1178 N GLU A 149 38, .477 13 .714 16, .553 1, .00 55. .77 7

ATOM 1179 CA GLU A 149 39. .233 14, .767 15, .884 1, .00 51, .96 6

ATOM 1180 CB GLU A 149 38, .384 16, .037 15, .821 1, .00 52, .02 6

ATOM 1181 CG GLU A 149 36, .918 15, .748 15, .527 1, .00 51, .38 6

ATOM 1182 CD GLU A 149 36. .065 16, .989 15. .423 1. .00 49. .98 6

ATOM 1183 OEl GLU A 149 36, .220 17, .879 16. .273 1, .00 50. .58 8

ATOM 1184 OE2 GLU A 149 35, .226 17, .070 14, .506 1, .00 46, .84 8

ATOM 1185 C GLU A 149 40 .531 15 .030 16, .627 1 .00 50, .15 6

ATOM 1186 O GLU A 149 41 .584 15 .167 16 .013 1 .00 49 .33 8

ATOM 1187 N- ILE A 150 40, .454 15 .100 17, .950 1, .00 47, .25 7

ATOM 1188 CA ILE A 150 41 .643 15 .309 18, .748 1 .00 48 .44 6

ATOM 1189 CB ILE A 150 41, .712 16 .740 19, .374 1, .00 48, .83 6

ATOM 1190 CG2 ILE A 150 42 .759 16 .793 20 .481 1, .00 44 .42 6

ATOM 1191 CGI ILE A 150 42 .104 17 .769 18 .316 1 .00 49 .22 6

ATOM 1192 CDl ILE A 150 42 .185 19 .175 18 .839 1 .00 45 .68 6

ATOM 1193 C ILE A 150 41 .707 14 .310 19 .881 1 .00 50 .37 6

ATOM 1194 O ILE A 150 40 .712 14 .031 20 .536 1 .00 50 .37 8

ATOM 1195 N SER A 151 42 .902 13 .781 20 .104 1 .00 52 .48 7

ATOM 1196 CA SER A 151 43 .156 12 .841 21 .178 1 .00 54 .49 6

ATOM 1197 CB SER A 151 43 .437 11 .452 20 .611 1 .00 54 .22 6

ATOM 1198 OG SER A 151 44 .619 11 .457 19 .844 1 .00 54 .28 8

ATOM 1199 C SER A 151 44 .385 13 .381 21 .899 1 .00 55 .57 6

ATOM 1200 O SER A 151 45 .347 13 .798 21 .257 1 .00 56 .29 8

ATOM 1201 N VAL A 152 44 .337 13 .400 23 .227 1 .00 57 .03 7

ATOM 1202 CA VAL A 152 45 .447 13 .897 24 .033 1 .00 59 .85 6

ATOM 1203 CB VAL A 152 44 .979 14 .922 25 .100 1 .00 59 .80 6

ATOM 1204 CGI VAL A 152 44 .170 16 .021 24 .447 1 .00 60 .14 6

ATOM 1205 CG2 VAL A 152 44 .163 14 .225 26 .175 1 .00 61 .09 6

ATOM 1206 C VAL A 152 46 .084 12 .722 24 .747 1 .00 61 .00 6

ATOM 1207 O VAL A 152 45 .393 11 .785 25 .132 1 .00 59 .83 8

ATOM 1208 N ASP A 153 47 .398 12 .780 24 .932 1 .00 63 .57 7

ATOM 1209 CA ASP A 153 48 .114 11 .690 25 .582 1 .00 66 .72 6 ATOM 1210 CB ASP A 153 48,.620 10,.724 24..505 1.,00 66,.16 6

ATOM 1211 CG ASP A 153 47. 505 10. ,245 23. .573 1. 00 67. ,72 6

ATOM 1212 ODl ASP A 153 46. .769 9. .317 23. .972 1. ,00 68. .96 8

ATOM 1213 OD2 ASP A 153 47. ,354 10. .801 22. .451 1. ,00 67. ,60 8

ATOM 1214 C ASP A 153 49. ,293 12. .198 26. .422 1. 00 68. ,93 6

ATOM 1215 O ASP A 153 49. .951 13. .175 26. .058 1. ,00 69. .39 8

ATOM 1216 N PRO A 154 49. .553 11, .564 27. .577 1. ,00 70. .74 7

ATOM 1217 CD PRO A 154 48. .601 10, .759 28. .357 1. .00 71. .40 6

ATOM 1218 CA PRO A 154 50, .675 11 .995 28, .421 1. .00 73, .42 6

ATOM 1219 CB PRO A 154 50, .421 11, .266 29, .735 1. .00 72. .22 6

ATOM 1220 CG PRO A 154 48, ,930 11, .182 29, .776 1, .00 72, .97 6

ATOM 1221 C PRO A 154 51. ,999 11. .580 27. .773 1. 00 75. ,99 6

ATOM 1222 0 PRO A 154 51. ,997 10, .951 26. .716 1. ,00 75, .49 8

ATOM 1223 N THR A 155 53. .121 11. .916 28. .406 1. ,00 79. .97 7

ATOM 1224 CA THR A 155 54, .433 11. .580 27, .851 1. .00 84, .54 6

ATOM 1225 CB THR A 155 55. .002 12. ,797 27. .084 1. ,00 84. .38 6

ATOM 1226 OG1 THR A 155 55 .314 13 .844 28. .015 1. .00 85, .24 8

ATOM 1227 CG2 THR A 155 53. ,979 13, .326 26. .085 1. ,00 83. .86 6

ATOM 1228 C THR A 155 55, .504 11, .101 28, .868 1. ,00 .88. .31 6

ATOM 1229 O THR A 155 55, .179 10, .480 29 .905 1. .00 89, .23 8

ATOM 1230 N THR A 156 56, .774 11, .402 28, .539 1. .00 91, .22 7

ATOM 1231 CA THR A 156 57, .970 11 .057 29 .337 1. .00 93, .64 6

ATOM 1232 CB THR A 156 59. .146 12, ,041 29. .041 1. ,00 93, ,80 6

ATOM 1233 OG1 THR A 156 59 .430 12 .048 27. .631 1. .00 93, .55 8

ATOM 1234 CG2 THR A 156 60. .414 11, ,624 29, .839 1. ,00 93. .12 6

ATOM 1235 C THR A 156 57, ,778 11, .031 30, .862 1. ,00 95, .49 6

ATOM 1236 O THR A 156 57, .812 12. .080 31, .532 1. ,00 95, .50 8

ATOM 1237 N GLU A 157 57, .614 9, .827 31, .406 1. ,00 97, ,12 7

ATOM 1238 CA GLU A 157 57, .411 9, .649 32, .841 1. .00 98, .24 6

ATOM 1239 CB GLU A 157 56, .619 8, .370 33, .095 1. .00100. .23 6

ATOM 1240 CG GLU A 157 55, .476 .8. .150 32, .109 1. ,00103, .23 6

ATOM 1241 CD GLU A 157 54 .728 6 .842 32 .372 1, .00104 .38 6

ATOM 1242 OE1 GLU A 157 55, .391 5. ,769 32. .462 1. ,00103. .49 8

ATOM 1243 OE2 GLU A 157 53, .475 6, .896 32. .482 1. ,00105, .11 8

ATOM 1244 C GLU A 157 58, .731 9, ,570 33, .591 1, ,00 98, .22 6

ATOM 1245 O GLU A 157 58, .742 9, .488 34, .825 1. .00 98, ,77 8

ATOM 1246 N ASN A 158 59, .840 9, .582 32, .854 1, ,00 97. .95 7

ATOM 1247 CA ASN A 158 61 .154 9 .505 33 .494 1. .00 98 .34 6

ATOM 1248 CB ASN A 158 62, .244 9, ,212 32, ,455 1. ,00100, .52 6

ATOM 1249 CG ASN A 158 61. .953 7, .969 31 .634 1, .00102. .32 6

ATOM 1250 ODl ASN A 158 61, .787 6, .872 32, .184 1. .00104. .16 8

ATOM 1251 ND2 ASN A 158 61, .898 8, .131 30, .305 1. .00102, .61 7

ATOM 1252 C ASN A 158 61 .471 10 .832 34 .196 1, .00 97, .02 6

ATOM 1253 O ASN A 158 61, .170 11, .019 35, .392 1, .00 96 . .34 8

ATOM 1254 N SER A 159 62 .093 11 .729 33 .423 1, .00 94 .95 7

ATOM 1255 CA SER A 159 62 .492 13, .069 33, .857 1, .00 91, .51 6

ATOM 1256 CB SER A 159 61. .878 14, .091 32. .890 1. .00 91, .99 6

ATOM 1257 OG SER A 159 60. .550 13, .708 32, .529 1. ,00 90, .83 8

ATOM 1258 C SER A 159 62. .116 13 .412 35, .301 1, ,00 88, ,77 6

ATOM 1259 O SER A 159 60 .939 13 .380 35 .666 1, .00 88 .38 8

ATOM 1260 N ASP A 160 63 .120 13, .728 36 .120 1, .00 85, .60 7

ATOM 1261 CA ASP A 160 62 .867 14 .093 37 .517 1, .00 81 .69 6

ATOM 1262 CB ASP A 160 64 .107 14, .716 38, .164 1, .00 81, .79 6

ATOM 1263 CG ASP A 160 63. .827 15. .217 39, .578 1, .00 82, .16 6

ATOM 1264 ODl ASP A 160 64 .609 16 .057 40 .075 1 .00 82 .93 8

ATOM 1265 OD2 ASP A 160 62 .824 14, .766 40, .194 1, .00 81, .33 8

ATOM 1266 C ASP A 160 61 .748 15, .125 37 .556 1 .00 78 .87 6

ATOM 1267 O ASP A 160 61. .906 16, .215 36, .997 1. .00 77, .29 8

ATOM 1268 N ASP A 161 60 .643 14, .783 38 .223 1, .00 75, .12 7

ATOM 1269 CA ASP A 161 59 .493 15, .677 38, .324 1. .00 71, .64 6

ATOM 1270 CB ASP A 161 58 .433 15, .111 39 .273 1, .00 71, .12 6 ATOM 1271 CG ASP A 161 57.719 13..895 38.,698 1.,00 71.,43 6

ATOM 1272 ODl ASP A 161 57. ,509 13. .854 37, ,463 1. ,00 70. .50 8

ATOM 1273 OD2 ASP A 161 57. ,353 12. ,983 39. .480 1. ,00 71. .76 8

ATOM 1274 C ASP A 161 59. ,814 17. ,097 38. .756 1. ,00 69. .97 6

ATOM 1275 O ASP A 161 59. ,009 18. ,001 38. .545 1. .00 69. .41 8

ATOM 1276 N SER A 162 60, ,974 17. .321 39. .358 1. .00 68. .43 7

ATOM 1277 CA SER A 162 61, .282 18. ,682 39, .774 1. ,00 68. .46 6

ATOM 1278 CB SER A 162 61, .190 18, .809 41, .308 1. .00 68. .76 6

ATOM 1279 OG SER A 162 62, .209 18, .069 41, .962 1. .00 68, .11 8

ATOM 1280 C SER A 162 62. .636 19. .163 39. .289 1. ,00 67. .78 6

ATOM 1281 O SER A 162 63, .264 20. .014 39. .917 1. .00 67. .84 8

ATOM 1282 N GLU A 163 63, .087 18. .640 38, .156 1, ,00 67. .60 7

ATOM 1283 CA GLU A 163 64, .382 19, .052 37, .649 1. ,00 68, .35 6

ATOM 1284 CB GLU A 163 64, .884 18, .051 36, .609 1, ,00 70. .48 6

ATOM 1285 CG GLU A 163 64, .380 18, .242 35, .193 1, .00 73. .24 . 6

ATOM 1286 CD GLU A 163 65, .111 17, .328 34, .204 1. .00 75. .50 6

ATOM 1287 OEl GLU A 163 64 .835 16 .097 34 .211 1, .00 76 .99 8

ATOM 1288 OE2 GLU A 163 65, .970 17, .842 33, .438 1. .00 73. .24 8

ATOM 1289 C GLU A 163 64 .342 20, .475 37, .083 1. ,00 68, .50 6

ATOM 1290 O GLU A 163 65 .385 21 .062 36 .774 1. .00 69, .25 8

ATOM 1291 N TYR A 164 63, .140 21. .031 36, .958 1. ,00 67. .44 7

ATOM 1292 CA TYR A 164 62, .968 22, .396 36, .466 1. ,00 65. .48 6

ATOM 1293 CB TYR A 164 62, .085 22, .422 35. .221 1. ,00 66. ,46 6

ATOM 1294 CG TYR A 164 62 .709 21 .754 34 .029 1. ,00 67, .56 6

ATOM 1295 CDl TYR A 164 62, .082 20, .664 33, .415 1, .00 68. .14 6

ATOM 1296 CEl TYR A 164 62, .664 20^', .011 32, .328 1. .00 67, .68 6

ATOM 1297 CD2 TYR A 164 63, .942 22, .185 33, .527 1. .00 66, .99 6

ATOM 1298 CE2 TYR A 164 64 .539 21, .538 32, .435 1, .00 69, .28 6

ATOM 1299 CZ TYR A 164 63 .892 20 .449 31 .837 1, .00 68 .44 6

ATOM 1300 OH TYR A 164 64 .456 19, .823 30, .737 1. ,00 69, .00 8

ATOM 1301 C TYR A 164 62 .313 23 .259 37 .534 1. ,00 64, .21 6

ATOM 1302 O TYR A 164 62 .181 24 .474 37 .368 1. .00 62, .71 8

ATOM 1303 N PHE A 165 61, .899 22, .626 38, .627 1. .00 62, .72 7

ATOM 1304 CA PHE A 165 61, .241 23, .343 39, .705 1, .00 60, .48 6

ATOM 1305 CB PHE A 165 60, .738 22, .364 40, .758 1. ,00 57, .99 6

ATOM 1306 CG PHE A 165 59 .676 22 .936 41 .641 1. ,00 57 .14 6

ATOM 1307 CDl PHE A 165 58, .424 23, .252 41 .115 1, ,00 55, .84 6

ATOM 1308 CD2 PHE A 165 59 .933 23 .194 42 .985 1, ,00 55 .03 6

ATOM 1309 CEl PHE A 165 57 .439 23 .818 41 .902 1, .00 54 .80 6

ATOM 1310 CE2 PHE A 165 58 .961 23, .762 43, .787 1. ,00 57, .75 6

ATOM 1311 CZ PHE A 165 57 .699 24 .079 43 .242 1, .00 57 .78 6

ATOM 1312 C PHE A 165 62, .159 24. .369 40_; .354 1. ,00 60, .44 6

ATOM 1313 O PHE A 165 63 .348 24 .121 40 .547 1. .00 60 .73 8

ATOM 1314 N SER A 166 61 .611 25 .534 40 .676 1, .00 60 .95 7

ATOM 1315 CA SER A 166 62 .418 26 .567 41 .312 1, .00 61 .11 6

ATOM 1316 CB SER A 166 61 .638 27 .874 41, .457 1. .00 59, .76 6

ATOM 1317 OG SER A 166 62 .476 28, .875 42, .015 1. .00 59, .79 8

ATOM 1318 C SER A 166 62 .809 26 .068 42 .694 1, .00 61 .38 6

ATOM 1319 O SER A 166 62 .009 25, .442 43, .393 1. . 00 ^'61, .62 8

ATOM 1320 N GLN A 167 64 .038 26 .359 43 .089 1 .00 61 .82 7

ATOM 1321 CA GLN A 167 64 .525 25 .931 44 .393 1 .00 62 .17 6

ATOM 1322 CB GLN A 167 66 .052 25 .797 44 .351 1, .00 63 .58 6

ATOM 1323 CG GLN A 167 •66 .745 27 .065 43 .861 1, .00 66 .42 6

ATOM 1324 CD GLN A 167 68 .204 26, .851 43. .514 1. .00 69, .06 6

ATOM 1325 OEl GLN A 167 69 .008 26 .488 44 .376 1. .00 70 .77 8

ATOM 1326 NΞ2 GLN A 167 68 .556 27 .081 42 .241 1, .00 69 .23 7

ATOM 1327 C GLN A 167 64 .119 26 .927 45 .476 1 .00 61 .22 6

ATOM 1328 O GLN A 167 64 .112 26 .585 46 .659 1 .00 61 .10 8

ATOM 1329 N TYR A 168 63 .762 28 .147 45 .075 1 .00 58 .44 7

ATOM 1330 CA TYR A 168 63 .392 29 .162 46 .046 1 .00 56 .45 6

ATOM 1331 CB TYR A 168 63 .881 30 .522 45 .564 1 .00 55 .36 6 ATOM 1332 CG TYR A 168 65.335 30.,469 45.158 1.00 57.58 6

ATOM 1333 CDl TYR A 168 65. 699 30. 352 43. 818 1. 00 57. 60 6

ATOM 1334 CEl TYR A 168 67. ,031 30. ,233 43. ,439 1. 00 57. 86 6

ATOM 1335 CD2 TYR A 168 66. 349 30. ,467 46. 115 1. 00 57. 43 6

ATOM 1336 CE2 TYR A 168 67. 683 30. 347 45. 749 1. 00 58. 19 6

ATOM 1337 CZ TYR A 168 68. .017 30. ,228 44. ,410 1. ,00 59. 25 6

ATOM 1338 OH TYR A 168 69 . 337 30. 086 44. 042 1. 00 60. 91 8

ATOM 1339 C TYR A 168 61. ,912 29. .199 46, ,383 1. .00 56. ,00 6

ATOM 1340 O TYR A 168 61. ,457 30. 053 47. 142 1. 00 56. 39 8

ATOM 1341 N SER A 169 61. .162 28. .257 45. .832 1. ,00 55. 67 7

ATOM 1342 CA SER A 169 59. .732 28. .179 46, ,096 1. .00 56. 31 6

ATOM 1343 CB SER A 169 59. ,082 27. ,123 45. ,197 1. ,00 57. 76 6

ATOM 1344 OG SER A 169 57. .699 26, .971 45, .501 1. .00 55. ,64 8

ATOM 1345 C SER A 169 59. ,478 27. ,804 47. ,544 1. ,00 57. 69 6

ATOM 1346 O SER A 169 60, .246 27. .066 48. .152 1. .00 58. ,82 8

ATOM 1347 N ARG A 170 58. ,385 28. ,302 48. ,096 1. .00 58. 68 7

ATOM 1348 CA ARG A 170 58, .043 27, .993 49, .472 1. .00 58. ,62 6

ATOM 1349 CB ARG A 170 56, .907 28, .901 49, .956 1. .00 60. ,14 6

ATOM 1350 CG ARG A 170 57. .371 30. ,123 50. ,727 1. ,00 60. ,43 6

ATOM 1351 CD ARG A 170 56, .401 31. .291 50. ,589 1. ,00 64. ,30 6

ATOM 1352 NE ARG A 170 55. .020 30. ,998 50. ,989 1. .00 66. ,31 7

ATOM 1353 CZ ARG A 170 53. .967 31, .107 50, ,174 1. .00 66. ,81 6

ATOM 1354 NHl ARG A 170 54. ,129 31, ,489 48. .915 1, ,00 63. ,97 7

ATOM 1355 NH2 ARG A 170 52, .750 30, ,850 50. .619 1, .00 67, ,23 7

ATOM 1356 C ARG A 170 57, .604 26, .544 49. .554 1. ,00 58. .75 6

ATOM 1357 O ARG A 170 57, ,516 25. ,975 50. ,642 1. ,00 60. ,59 8

ATOM 1358 N PHE A 171 57, .339 25, .933 48, .405 1, .00 57. .02 7

ATOM 1359 CA PHE A 171 56, ,882 24, ,552 48. .404 1. ,00 56. ,54 6

ATOM 1360 CB PHE A 171 55 .499 24 .479 47 .765 1 .00 55, .41 6

ATOM 1361 CG PHE A 171 54, .552 25. .522 48. .281 1. ,00 55. ,91 6

ATOM 1362 CDl PHE A 171 54, .685 26, .856 47. .893 1. .00 57. .70 6

ATOM 1363 CD2 PHE A 171 53 .560 25 .190 49, .203 1, ,00 56. .28 6

ATOM 1364 CEl PHE A 171 53. .845 27. .847 48. .419 1. . 00 58. ,19 6

ATOM 1365 CE2 PHE A 171 52 .718 26, .170 49. .732 1, .00 55. .91 6

ATOM 1366 CZ PHE A 171 52. .864 27, .505 49, .337 1, ,00 57. .16 6

ATOM 1367 C PHE A 171 57 .844 23, .612 47. .695 1, ,00 56. .77 6

ATOM 1368 O PHE A 171 58. .841 24, .045 47, .113 1, .00 56, .03 8

ATOM 1369 N GLU A 172 57 .552 22 .319 47 .765 1, .00 56. .23 7

ATOM 1370 CA GLU A 172 58 .389 21 .325 47 .120 1 .00 58 .00 6

ATOM 1371 CB GLU A 172 59 .371 20, .707 48. .119 1, .00 60, ,23 6

ATOM 1372 CG GLU A 172 58 .734 19 .970 49 .303 1 .00 64 .00 6

ATOM 1373 CD GLU A 172 59. .769 19, .445 50, .313 1, .00 66, .01 6

ATOM 1374 OEl GLU A 172 60 .869 19 .042 49 .868 1 .00 69 .59 8

ATOM 1375 OE2 GLU A 172 59 .487 19 .421 51 .541 1 .00 65 .33 8

ATOM 1376 C GLU A 172 57 .497 20 .259 46 .518 1 .00 59 .67 6

ATOM 1377 O GLU A 172 56 .356 20 .064 46 .955 1 .00 60 .12 8

ATOM 1378 N ILE A 173 58 .006 19 .579 45 .496 1 .00 60 .16 7

ATOM 1379 CA ILE A 173 57 .224 18 .545 44 .827 1 .00 60 .67 6

ATOM 1380 CB ILE A 173 57 .413 18 .587 43 .291 1 .00 61 .87 6

ATOM 1381 CG2 ILE A 173 56 .659 17 .422 42 .644 1 .00 62 .56 6

ATOM 1382 CGI ILE A 173 56 .920 19 .919 42 .727 1 .00 61 .03 6

ATOM 1383 CDl ILE A 173 57 .165 20 .062 41 .244 1 .00 59 .49 6

ATOM 1384 C ILE A 173 57 .579 17 .150 45 .296 1 .00 59 .83 6

ATOM 1385 O ILE A 173 58 .751 16 .770 45 .360 1 .00 57 .21 8

ATOM 1386 N LEU A 174 56 .554 16 .381 45 .616 1 .00 61 .63 7

ATOM 1387 CA LEU A 174 56 .786 15 .022 46 .056 1 .00 64 .20 6

ATOM 1388 CB LEU A 174 55 .687 14 .592 47 .024 1 .00 63 .47 6

ATOM 1389 CG LEU A 174 55 .461 15 .601 48 .149 1 .00 65 .34 6

ATOM 1390 CDl LEU A 174 54 .285 15 .144 49 .024 1 .00 66 .19 6

ATOM 1391 CD2 LEU A 174 56 .747 15 .770 48 .962 1 .00 64 .00 6

ATOM 1392 C LEU A 174 56 .783 14 .147 44 .806 1 .00 65 .92 6 ATOM 1393 O LEU A 174 57..757 13.,440 44..522 1.00 65.,29 8

ATOM 1394 N ASP A 175 55. 702 14. 233 44. ,036 1. 00 67. 33 7

ATOM 1395 CA ASP A 175 55. ,583 13. ,436 42. .827 1. 00 68. ,45 6

ATOM 1396 CB ASP A 175 55. 227 11. ,993 43. .223 1. 00 68. ,56 6

ATOM 1397 CG ASP A 175 55. .161 11. ,038 42. ,032 1. ,00 68. .23 6

ATOM 1398 ODl ASP A 175 56. ,141 10. .964 41. ,244 1. ,00 67, .58 8

ATOM 1399 OD2 ASP A 175 54, .121 10. .347 41, ,905 1. ,00 67, .56 8

ATOM 1400 C ASP A 175 54. .542 14, .023 41, .872 1. .00 69. .02 6

ATOM 1401 O ASP A 175 53. .617 14. .735 42. .286 1. 00 69, ,85 8

ATOM 1402 N VAL A 176 54, ,714 13. .727 40. .587 1. .00 68. .72 7

ATOM 1403 CA VAL A 176 53, ,809 14, .198 39, .552 1. .00 67. .76 6

ATOM 1404 CB VAL A 176 54. ,461 15. ,324 38. .694 1. 00 67. ,60 6

ATOM 1405 CGI VAL A 176 53. .533 15. ,721 37. ,542 1. ,00 66. ,09 6

ATOM 1406 CG2 VAL A 176 54, .771 16. .532 39 .564 1, ,00 65. .31 6

ATOM 1407 C VAL A 176 53, .495 13. .025 38. .645 1. .00 67, .31 6

ATOM 1408 O VAL A 176 54. .399 12. .308 38, ,230 1. ,00 66, ,10 8

ATOM 1409 N THR A 177 52 .213 12, .833 38 .348 1. .00 68, .30 7

ATOM 1410 CA THR A 177 51, .781 11. .763 37, .463 1. ,00 69. .37 6

ATOM 1411 CB THR A 177 51, .241 10. .565 38, .259 1, ,00 69, .49 6

ATOM 1412 OG1 THR A 177 50 .218 11, .007 39 .160 1, .00 69, .60 8

ATOM 1413 CG2 THR A 177 52. .366 9. .905 39, .045 1. ,00 69, ,19 6

ATOM 1414 C THR A 177 50. .696 12, .276 36, .528 1. .00 70, ,72 6

ATOM 1415 O THR A 177 49, .879 13, .119 36, .917 1, .00 72, .04 8

ATOM 1416 N GLN A 178 50 .692 11, .771 35 .297 1, .00 71 .85 7

ATOM 1417 CA GLN A 178 49 .706 12 .191 34 .302 1, .00 73 .03 6

ATOM 1418 CB GLN A 178 50, .392 12. .916 33, .144 1. ,00 75, .20 6

ATOM 1419 CG GLN A 178 51, .681 13, .640 33 .533 1. .00 78, .41 6

ATOM 1420 CD GLN A 178 52, .059 14, .733 32 .539 1, .00 79, .92 6

ATOM 1421 OEl GLN A 178 52, .078 14, .509 31, .315 1. .00 81, .52 8

ATOM 1422 NE2 GLN A 178 52, .370 15. ,924 33, .061 1, .00 78. .36 7

ATOM 1423 C GLN A 178 49 .014 10, .964 33 .764 1. .00 72 .67 6

ATOM 1424 O GLN A 178 49 .679 10, .043 33, .293 1. .00 73, .74 8

ATOM 1425 N LYS A 179 47 .686 10 .947 33 .827 1, .00 72 .17 7

ATOM 1426 CA LYS A 179 46 .916 9 .807 33 .337 1, .00 71 .53 6

ATOM 1427 CB LYS A 179 46. .327 9. ,038 34, .519 1, .00 74, .09 6

ATOM 1428 CG LYS A 179 47 .352 8 .781 35 .644 1, .00 79 .46 6

ATOM 1429 CD LYS A 179 46 .703 8, .189 36 .905 1. .00 81, .06 6

ATOM 1430 CE LYS A 179 47 .635 8, .300 38 .119 1. .00 80 .77 6

ATOM 1431 NZ LYS A 179 47 .968 9 .715 38 .443 1, .00 80 .83 7

ATOM 1432 C LYS A 179 45 .795 10, .316 32 .470 1. .00 70, .00 6

ATOM 1433 O LYS A 179 44 .878 10, ,939 32, .980 1, . 00 73, .37 8

ATOM 1434 N LYS A 180 45 .845 10 .060 31 .170 1, .00 67 .55 7

ATOM 1435 CA LYS A 180 44 .780 10 .538 30 .294 1 .00 67 .72 6

ATOM 1436 CB LYS A 180 45 .171 10 .327 28 .829 1 .00 66 .54 6

ATOM 1437 CG LYS A 180 45 .120 8 .909 28 .344 1 .00 63 .87 6

ATOM 1438 CD LYS A 180 43 .751 8 .573 27 .796 1 .00 64 .72 6

ATOM 1439 CE LYS A 180 43 .404 9 .412 26 .552 1 .00 65 .43 6

ATOM 1440 NZ LYS A 180 44 .217 9 .057 25 .339 1, .00 65 .01 7

ATOM 1441 C LYS A 180 43 .445 9 .854 30 .586 1, .00 67 .22 6

ATOM 1442 O LYS A 180 43 .373 9 .021 31 .471 1 .00 68 .12 8

ATOM 1443 N ASN A 181 42 .388 10, .231 29. .871 1, .00 67 .59 7

ATOM 1444 CA ASN A 181 41 .083 9 .600 30 .053 1 .00 68 .03 6

ATOM 1445 CB ASN A 181 40 .710 9 .514 31 .545 1 .00 69 .44 6

ATOM 1446 CG ASN A 181 40 .940 10 .803 32 .291 1 .00 68 .81 6

ATOM 1447 ODl ASN A 181 40 .552 11 .872 31 .834 1 .00 71 .29 8

ATOM 1448 ND2 ASN A 181 41 .556 10 .706 33 .463 1 .00 67 .88 7

ATOM 1449 C ASN A 181 39 .917 10 .194 29 .272 1 .00 67 .66 6

ATOM 1450 O ASN A 181 39 .576 11 .350 29 .437 1 .00 68 .16 8

ATOM 1451 N SER A 182 39 .302 9 .377 28 .420 1 .00 68 .81 7

ATOM 1452 CA SER A 182 38 .160 9 .802 27 .615 1 .00 68 .00 6

ATOM 1453 CB SER A 182 37 .861 8 .745 26 .553 1 .00 67 .42 6 Ό

ATOM 1454 OG SER A 182 36. ,905 9. .223 25. .626 1. 00 70. ,87 8

ATOM 1455 C SER A 182 36. ,953 9. .974 28. .541 1. 00 67. 36 6

ATOM 1456 O SER A 182 36. .915 9, .385 29, .617 1. .00 67. .61 8

ATOM 1457 N VAL A 183 35. ,973 10. ,771 28. .126 1. 00 65. ,82 7

ATOM 1458 CA VAL A 183 34. ,790 11. .017 28. .950 1. ,00 64. ,66 6

ATOM 1459 CB VAL A 183 35. .151 11. ,912 30. .163 1. ,00 63. ,68 6

ATOM 1460 CGI VAL A 183 36. .153 12. .956 29, .748 1. ,00 65. .08 6

ATOM 1461 CG2 VAL A 183 33. .901 12. .581 30. .718 1. .00 61, .80 6

ATOM 1462 C VAL A 183 33. .632 11. .666 28, .204 1. .00 64. .12 6

ATOM 1463 O VAL A 183 33. .828 12. .597 27. ,440 1. .00 64. ,83 8

ATOM 1464 N THR A 184 32, .422 11, ,170 28. .432 1. .00 65. ,00 7

ATOM 1465 CA THR A 184 31. .240 11, .737 27, ,793 1. ,00 67, ,07 6

ATOM 1466 CB THR A 184 30. .303 10, .641 27, .258 1. ,00 64. ,63 6

ATOM 1467 OG1 THR A 184 30. .977 9. .911 26, .224 1. ,00 61, .46 8

ATOM 1468 CG2 THR A 184 29. .030 11, .260 26, ,685 1, .00 67. ,30 6

ATOM 1469 C THR A 184 30. ,490 12. .596 28, .808 1. ,00 69. .96 6

ATOM 1470 O THR A 184 30, .413 12, .238 29, .993 1, .00 71. .87 8

ATOM 1471 N TYR A 185 29. .961 13, .735 28, .362 1. .00 .71. .00 7

ATOM 1472 CA TYR A 185 29, .230 14. .618 29. .261 1. ,00 72. .17 6

ATOM 1473 CB TYR A 185 29. .849 16, ,015 29, .274 1. .00 72. ,39 6

ATOM 1474 CG TYR A 185 31, ,335 16, .005 29, .525, 1. .00 72, .53 6

ATOM 1475 CDl TYR A 185 32 .226 15 .598 28 .531 1, .00 71, .50 6

ATOM 1476 CEl TYR A 185 33, .601 15, .535 28, .775 1, . 00 70, .43 6

ATOM 1477 CD2 TYR A 185 31 .854 16 .358 30 .776 1, .00 73 .42 6

ATOM 1478 CΞ2 TYR A 185 33, .236 16, .300 31, .031 1, .00 71 .16 6

ATOM 1479 CZ TYR A 185 34, .097 15, .885 30, .022 1, .00 70, .35 6

ATOM 1480 OH TYR A 185 35, .448 15. .811 30, .254 1, .00 68. . 69 8

ATOM 1481 C TYR A 185 27, .804 14, .705 28, .780 1. .00 73, .84 6

ATOM 1482 O TYR A 185 27. .551 14, .756 27, .576 1. .00 73 .39 8

ATOM 1483 N SER A 186 26, .873 14, .714 29, .727 1. .00 76, .31 7

ATOM 1484 CA SER A 186 25. .455 14 .794 29, .403 1, .00 78 .23 6

ATOM 1485 CB SER A 186 24 .645 14 .953 30 .693 1, .00 78 .92 6

ATOM 1486 OG SER A 186 25, .215 15, .952 31. .527 1. .00 77, .75 8

ATOM 1487 C SER A 186 25 .197 15 .967 28 .453 1. .00 78 .29 6

ATOM 1488 O SER A 186 24, .348 15, .879 27, .553 1. .00 79, .09 8

ATOM 1489 N CYS A 187 25 .949 17 .047 28 .653 1. .00 77 .81 7

ATOM 1490 CA CYS A 187 25, .830 18, .254 27, .839 1. .00 78, .71 6

ATOM 1491 C CYS A 187 26 .144 17 .978 26 .407 1, .00 78 .06 6

ATOM 1492 O CYS A 187 25, .514 18, .482 25, .488 1. .00 78, .32 8

ATOM 1493 CB CYS A 187 26, .858 19, .320 28, ,252 1. .00 79 .52 6

ATOM 1494 SG CYS A 187 28 .656 18 .934 27 .946 1 .00 82 .56 16

ATOM 1495 N CYS A 188 27, .147 17, .144 26, .244 1, .00 ^■78, . 96 7

ATOM 1496 CA CYS A 188 27 .706 16 .918 24 .947 1 .00 78 .72 6

ATOM 1497 C CYS A 188 27. .817 15, .468 24, .454 1, .00 78 .19 6

ATOM 1498 O CYS A 188 28 .454 14 .618 25 .096 1 .00 78 .27 8

ATOM 1499 CB CYS A 188 29, .070 17, .610 25, .006 1, .00 79 . 96 6

ATOM 1500 SG CYS A 188 29 .118 19. .206 25, .950 1, .00 80 .88 16

ATOM 1501 N PRO A 189 27 .211 15. .186 23, .281 1. .00 77 .44 7

ATOM 1502 CD PRO A 189 26 .571 16. .283 22, .526 1, .00 77 .01 6

ATOM 1503 CA PRO A 189 27. .125 13. .918 22, .532 1, .00 76 .01 6

ATOM 1504 CB PRO A 189 26 .756 14 .378 21 .129 1. .00 76 .94 6

ATOM 1505 CG PRO A 189 25 .858 15 .558 21 .408 1 .00 77 .54 6

ATOM 1506 C PRO A 189 28 .355 12 .991 22, .512 1, .00 75 .22 6

ATOM 1507 O PRO A 189 28. .300 11. .883 23, .056 1, .00 76 .90 8

ATOM 1508 N GLU A 190 29 .447 13 .423 21 .874 1 .00 72 .83 7

ATOM 1509 CA GLU A 190 30 .662 12, .603 21, .768 1, .00 69 .68 6

ATOM 1510 CB GLU A 190 31 .535 13 .102 20 .629 1 .00 72 .91 6

ATOM 1511 CG GLU A 190 30 .777 13, .743 19, .486 1, .00 75 .89 6

ATOM 1512 CD GLU A 190 30 .236 12 .730 18 .505 1 .00 77 .90 6

ATOM 1513 OEl GLU A 190 30 .974 11 .765 18 .170 1 .00 78 .51 8

ATOM 1514 OE2 GLU A 190 29 .080 12 .909 18 .058 1 .00 79 .55 8 ATOM 1515 C GLU A 190 31.492 12.631 23.039 1.00 66.30 6

ATOM 1516 O GLU A 190 31. 113 13. 278 24. 009 1. 00 65. 23 8

ATOM 1517 N ALA A 191 32. 633 11. 941 23. 020 1. 00 63. 17 7

ATOM 1518 CA ALA A 191 33. 524 11. 891 24. 182 1. 00 61. 94 6

ATOM 1519 CB ALA A 191 34. 102 10. 493 24. 341 1. 00 60. 63 6

ATOM 1520 C ALA A 191 34. 666 12. 904 24. ,055 1. 00 61. ,30 6

ATOM 1521 O ALA A 191 35. 148 13. 165 22. 950 1. 00 62. ,21 8

ATOM 1522 N TYR A 192 35. 105 13. ,468 25. .179 1. 00 58. ,30 7

ATOM 1523 CA TYR A 192 36. 188 14. ,438 25. ,159 1. 00 56. ,19 6

ATOM 1524 CB TYR A 192 35. ,695 15. ,807 25. .633 1. ,00 55, .84 6

ATOM 1525 CG TYR A 192 34. .779 16. ,487 24. ,649 1. 00 56. ,15 6

ATOM 1526 CDl TYR A 192 33. 409 16. 226 24. ,642 1. 00 56. ,04 6

ATOM 1527 CEl TYR A 192 32, .571 16. .794 23, .683 1. ,00 57, .88 6

ATOM 1528 CD2 TYR A 192 35. 291 17. ,341 23. ,675 1. 00 56. ,39 6

ATOM 1529 CE2 TYR A 192 34. .467 17. .915 22, .715 1. ,00 57, ,19 6

ATOM 1530 CZ TYR A 192 33. ,108 17. ,637 22. ,722 1. 00 58. ,29 6

ATOM 1531 OH TYR A 192 32. .295 18. .200 21, .769 1. .00 58, .06 8

ATOM 1532 C TYR A 192 37. ,389 14. .013 25. ,984 1. 00 56. ,62 6

ATOM 1533 0 TYR A 192 37. ,375 14. .090 27. .217 1. ,00 57. .67 8

ATOM 1534 N GLU A 193 38. ,436 13. ,571 25. .291 1. ,00 57. ,15 7

ATOM 1535 CA GLU A 193 39. .676 13. .124 25. .935 1. ,00 58, ,07 6

ATOM 1536 CB GLU A 193 40. .651 12. .523 24, .901 1. .00 56, .63 6

ATOM 1537 CG GLU A 193 40. .143 11. .269 24. .209 1. .00 55. .92 6

ATOM 1538 CD GLU A 193 41. .171 10. ,636 23. .307 1. .00 56. .05 6

ATOM 1539 OEl GLU A 193 42. .339 10, .509 23, .743 1. .00 56, ,33 8

ATOM 1540 OE2 GLU A 193 40. .808 10. .250 22. .171 1. ,00 57, .19 8

ATOM 1541 C GLU A 193 40. .363 14. .278 26. .655 1. .00 58. .09 6

ATOM 1542 O GLU A 193 40. .221 15, .440 26 .261 1, .00 59 .15 8

ATOM 1543 N ASP A 194 41, .098 13, .948 27, .712 1, .00 57, .73 7

ATOM 1544 CA ASP A 194 41 .816 14, .941 28 .486 1, .00 56 .31 6

ATOM 1545 CB ASP A 194 40, .856 15, .738 29, .386 1. .00 57 .85 6

ATOM 1546 CG ASP A 194 40 .339 14 .930 30 .578 1. .00 59 .72 6

ATOM 1547 ODl ASP A 194 39, .120 14. .610 30. .592 1. .00 55, .87 8

ATOM 1548 OD2 ASP A 194 41 .154 14 .628 31 .494 1, .00 58 .60 8

ATOM 1549 C ASP A 194 42 .881 14, .276 29 .333 1, ,00 55 .87 6

ATOM 1550 O ASP A 194 42 .746 13 .121 29 .714 1, .00 56 .72 8

ATOM 1551 N VAL A 195 43 .948 15, .014 29 .611 1. .00 55 .00 7

ATOM 1552 CA VAL A 195 45 .039 14 .520 30 .431 1, .00 55 .58 6

ATOM 1553 CB VAL A 195 46 .397 14, .961 29 .876 1, .00 54 .15 6

ATOM 1554 CGI VAL A 195 47 .508 14, .610 30 .860 1, .00 52 .00 6

ATOM 1555 CG2 VAL A 195 46 .643 14 .292 28 .544 1, .00 53 .83 6

ATOM 1556 C VAL A 195 44 .900 15, .082 31, .832 1. .00 57 .46 6

ATOM 1557 O VAL A 195 44 .809 16 .294 32 .011 1. .00 57 .93 8

ATOM 1558 N GLU A 196 44 .886 14 .206 32 .828 1, .00 58 .46 7

ATOM 1559 CA GLU A 196 44 .767 14 .654 34 .204 1 .00 58 .24 6

ATOM 1560 CB GLU A 196 43 .805 13 .758 34 .966 1 .00 59 .77 6

ATOM 1561 CG GLU A 196 43 .556 14 .199 36 .385 1, .00 63 .27 6

ATOM 1562 CD GLU A 196 42 .624 13 .256 37 .114 1 .00 64 .52 6

ATOM 1563 OEl GLU A 196 41 .485 13 .063 36 .646 1 .00 63 .73 8

ATOM 1564 OE2 GLU A 196 43 .035 12 .705 38 .155 1 .00 68 .58 8

ATOM 1565 C GLU A 196 46 .142 14 .590 34 .828 1 .00 57 .57 6

ATOM 1566 0 GLU A 196 46 .775 13 .538 34 .841 1 .00 59 .03 8

ATOM 1567 N VAL A 197 46 .618 15 .723 35 .322 1 .00 55 .78 7

ATOM 1568 CA VAL A 197 47 .929 15 .766 35 .943 1 .00 55 .65 6

ATOM 1569 CB VAL A 197 48 .781 16 .937 35 .386 1 .00 55 .24 6

ATOM 1570 CGI VAL A 197 50 .142 16 .962 36 .050 1 .00 51 .21 6

ATOM 1571 CG2 VAL A 197 48 .929 16 .800 33 .877 1 .00 53 .65 6

ATOM 1572 C VAL A 197 47 .716 15 .955 37 .431 1 .00 57 .58 6

ATOM 1573 0 VAL A 197 46 .963 16 .843 37 .850 1 .00 57 .66 8

ATOM 1574 N SER A 198 48 .355 15 .102 38 .231 1 .00 58 .29 7

ATOM 1575 CA SER A 198 48 .229 15 .194 39 .677 1 .00 57 .91 6 '0

ATOM 1576 CB SER A 198 47. 951 13, ,822 40. ,275 1. 00 56. ,54 6

ATOM 1577 OG SER A 198 46. 654 13. .401 39. 908 1. 00 61. ,46 8

ATOM 1578 C SER A 198 49. ,501 15. ,765 40. .257 1. ,00 58. ,27 6

ATOM 1579 O SER A 198 50. ,585 15, ,202 40. ,089 1. 00 58. ,63 8

ATOM 1580 N LEU A 199 49. .366 16. .901 40. ,929 1. 00 58. ,53 7

ATOM 1581 CA LEU A 199 50, ,521 17. .538 41. ,531 1. ,00 60. .77 6

ATOM 1582 CB LEU A 199 50. ,519 19. .046 41, ,274 1. ,00 60. .73 6

ATOM 1583 CG LEU A 199 51. .591 19, .833 42. .032 1. ,00 59, ,19 6

ATOM 1584 CDl LEU A 199 52. 982 19. .400 41. ,599 1. 00 57. ,61 6

ATOM 1585 CD2 LEU A 199 51. .390 21. .311 41. ,776 1. ,00 60, ,66 6

ATOM 1586 C LEU A 199 50. .524 17. .293 43. .022 1. ,00 61, .78 6

ATOM 1587 O LEU A 199 49. ,739 17. .895 43. ,765 1. ,00 62. ,31 8

ATOM 1588 N ASN A 200 51. ,397 16. .389 43. ,457 1. ,00 61. .40 7

ATOM 1589 CA ASN A 200 51. ,519 16, ,092 44. ,866 1. ,00 58. .00 6

ATOM 1590 CB ASN A 200 51. .763 14, .607 45. .088 1, ,00 60, .46 6

ATOM 1591 CG ASN A 200 51. .926 14, .267 46. .553 1. ,00 61, .99 6

ATOM 1592 ODl ASN A 200 51. .158 14 .735 47. .391 1. .00 63. .14 8

ATOM 1593 ND2 ASN A 200 52, .928 13, .447 46. .871 1. .00 63. .54 7

ATOM 1594 C ASN A 200 52. ,708 16, .906 45. .345 1, ,00 56, .52 6

ATOM 1595 O ASN A 200 53. .859 16, .664 44, .957 1, .00 55, .31 8

ATOM 1596 N PHE A 201 52. .406 17, .901 46. .166 1. .00 55, .49 7

ATOM 1597 CA PHE A 201 53, .416 18 .790 46, .707 1. .00 54 .84 6

ATOM ¹ 1598 CB PHE A 201 53, .450 20 .082 45, ,908 1. .00 50, .77 6

ATOM 1599 CG PHE A 201 52, .237 20, .940 46, .112 1. ,00 47, .21 6

ATOM 1600 CDl PHE A 201 52, .337 22 .161 46, .765 1, .00 46 .20 6

ATOM 1601 CD2 PHE A 201 50, .985 20 .513 45, .678 1. ,00 46, .31 6

ATOM 1602 CEl PHE A 201 51, .205 22, .942 46, .984 1. .00 45, .24 6

ATOM 1603 CE2 PHE A 201 49. .849 21, .291 45. .896 1. .00 43, ,16 6

ATOM 1604 CZ PHE A 201 49, ,962 22, .504 46. .549 1, .00 42, .59 6

ATOM 1605 C PHE A 201 53, .035 19, .112 48, .142 1, ,00 56, .47 6

ATOM 1606 O PHE A 201 51, .956 18 .748 48, .610 1, .00 54, .75 8

ATOM 1607 N ARG A 202 53, .927 19 .811 48, .829 1. .00 58, .72 7

ATOM 1608 CA ARG A 202 53, ,693 20, .207 50, .207 1. .00 61, .75 6

ATOM 1609 CB ARG A 202 54, .052 19 .063 51, .136 1, .00 63, .76 6

ATOM 1610 CG ARG A 202 55. .544 18 .822 51, .130 1, .00 65, .86 6

ATOM 1611 CD ARG A 202 55 .938 17 .640 51 .962 1, .00 68 .52 6

ATOM 1612 NE ARG A 202 57, .383 17 .466 51, .916 1, .00 69, .87 7

ATOM 1613 CZ ARG A 202 58, .013 16 .409 52, .405 1, .00 70, .56 6

ATOM 1614 NHl ARG A 202 57 .308 15 .433 52 .977 1 .00 71 .39 7

ATOM 1615 NH2 ARG A 202 59 .340 16 .332 52 .315 1, .00 70 .56 7

ATOM 1616 C ARG A 202 54, .579 21 .406 50, .556 1, .00 62 .74 6

ATOM 1617 O ARG A 202 55, .588 21 .675 49 .890 1 .00 62 .41 8

ATOM 1618 N LYS A 203 54 .200 22 .121 51 .606 1. .00 63 .53 7

ATOM 1619 CA LYS A 203 54 .983 23 .256 52 .044 1 .00 64 .89 6

ATOM 1620 CB LYS A 203 54 .271 23 .993 53 .169 1 .00 65 .59 6

ATOM 1621 CG LYS A 203 55, .067 25 .149 53, .740 1 .00 66 .14 6

ATOM 1622 CD LYS A 203 54 .348 25 .777 54, .911 1, .00 65, .85 6

ATOM 1623 CE LYS A 203 55 .145 26 .939 55 .473 1 .00 67 .46 6

ATOM 1624 NZ LYS A 203 55 .259 28 .073 54, .500 1 .00 68 .09 7

ATOM 1625 C LYS A 203 56 .264 22 .665 52 .563 1 .00 65 .93 6

ATOM 1626 0 LYS A 203 56 .250 21 .585 53 .157 1 .00 66 .11 8

ATOM 1627 N LYS A 204 57 .372 23 .351 52 .313 1, .00 69, .05 7

ATOM 1628 CA LYS A 204 58 .659 22 .863 52 .767 1 .00 71 .58 6

ATOM 1629 CB LYS A 204 59 .758 23 .834 52 .358 1 .00 ^'69 .66 6

ATOM 1630 CG LYS A 204 59 .862 23 .906 50 .839 1 .00 69 .91 6

ATOM 1631 CD LYS A 204 61 .113 24 .609 50 .336 1 .00 71 .48 6

ATOM 1632 CE LYS A 204 61 .195 24 .491 48 .809 1 .00 73 .18 6

ATOM 1633 NZ LYS A 204 62 .324 25 .234 48 .189 1 .00 72 .99 7

ATOM 1634 C LYS A 204 58 .544 22 .745 54 .264 1 .00 74 .56 6

ATOM 1635 O LYS A 204 57 .769 23 .493 54 .873 1 .00 77 .21- 8

ATOM 1636 N GLY A 205 59 .262 21 .782 54 .850 1 .00 75 .75 7 ATOM 1637 CA GLY A 205 59.,215 21..592 56.,296 1.00 75.55 6

ATOM 1638 C GLY A 205 60. 125 22. .564 57. ,029 1. 00 76. 09 6

ATOM 1639 OT1 GLY A 205 60. ,824 23. ,350 56. ,348 1. 00 77. 07 8

ATOM 1640 OT2 GLY A 205 60. ,151 22. .545 58. .278 1. 00 75. ,36 8

ATOM 1641 CB PHE B 1 33. ,107 19. .922 1. ,832 1. 00 57. 02 6

ATOM 1642 CG PHE B 1 32. .174 20, .672 0. .888 1. ,00 58, ,55 6

ATOM 1643 CDl PHE B 1 32. ,670 21, .495 -0. ,120 1. 00 59. 39 6

ATOM 1644 CD2 PHE B 1 30, ,784 20, .612 1. .079 1. ,00 58. ,84 6

ATOM 1645 CEl PHE B 1 31, .795 22, .248 -0. .919 1. ,00 59. .92 6

ATOM 1646 CE2 PHE B 1 29. ,905 21. ,357 0. .292 1. 00 56. ,97 6

ATOM 1647 CZ PHE B 1 30. .410 22, .176 -0. .707 1. ,00 58. .52 6

ATOM 1648 C PHE B 1 35. .200 18. ,747 2. ,262 1. 00 56. 22 6

ATOM 1649 O PHE B 1 34, .732 18, ,314 3. .311 1. ,00 58. .27 8

ATOM 1650 N PHE B 1 33. .748 17, .916 0. .462 1. ,00 54. ,28 7

ATOM 1651 CA PHE B 1 34. .250 19, .143 1. .152 1. ,00 55. ,90 6

ATOM 1652 N ASP B 2 36, .512 18 .877 2, .083 1. ,00 55. .99 7

ATOM 1653 CA ASP B 2 37. .383 18, .526 3. ,204 1. ,00 56. ,44 6

ATOM 1654 CB ASP B 2 38. .876 18, .485 2, .792 1. ,00 59. .88 6

ATOM 1655 CG ASP B 2 39. .364 19, .782 2. ,139 1. ,00 65. ,04 6

ATOM 1656 ODl ASP B 2 40 .076 19 .729 1. .091 1. .00 67, ,12 8

ATOM 1657 OD2 ASP B 2 39, .042 20, .860 2, .684 1, ,00 68. .18 8

ATOM 1658 C ASP B 2 37 .096 19 .582 4 .280 1. .00 55, .70 6

ATOM 1659 O ASP B 2 36, .331 20, .507 4, .047 1. ,00 54. .61 8

ATOM 1660 N ARG B 3 37, .682 19, .443 5. .458 1. 00 55. .52 7

ATOM 1661 CA ARG B 3 37, .441 20, .380 6. .556 1. ,00 53. ,72 6

ATOM 1662 CB ARG B 3 38. .114 19, .838 7. ,806 1. ,00 56. ,23 6

ATOM 1663 CG ARG B 3 37 .541 20 .323 9 .094 1. ,00 55, .76 6

ATOM 1664 CD ARG B 3 37, .772 19, .269 10, .139 1, ,00 55. .83 6

ATOM 1665 NE ARG B 3 36, .531 18 .930 10, .818 1. .00 56. .35 7

ATOM 1666 CZ ARG B 3 36, .233 17, ,708 11, .220 1. ,00 56. .91 6

ATOM 1667 NHl ARG B 3 37 .095 16 .729 10. .994 1. ,00 56. .22 7

ATOM 1668 NH2 ARG B 3 35 .090 17, .468 11. .849 1. .00 57, .84 7

ATOM 1669 C ARG B 3 37, .909 21, .822 6, .295 1. ,00 53. .67 6

ATOM 1670 O ARG B 3 37 .395 22 .772 6 .888 1. .00 53, .80 8

ATOM 1671 N ALA B 4 38, .896 21, .969 5, .420 1. ,00 52. .29 7

ATOM 1672 CA ALA B 4 39 .443 23 .255 5 .025 1, .00 50, .06 6

ATOM 1673 CB ALA B 4 40 .743 23, .036 4, .275 1, .00 48, .42 6

ATOM 1674 C ALA B 4 38 .442 23 .978 4, .131 1. ,00 49. .06 6

ATOM 1675 O ALA B 4 38 .225 25 .179 4 .270 1, ,00 47 .12 8

ATOM 1676 N ASP B 5 37 .837 23 .233 3 .211 1. ,00 49, .07 7

ATOM 1677 CA ASP B 5 36 .869 23 .801 2, .288 1. .00 51, .75 6

ATOM 1678 CB ASP B 5 36 .345 22 .748 1 .299 1, ,00 55, .02 6

ATOM 1679 CG ASP B 5 37 .454 22 .084 0 .491 1. .00 60 .18 6

ATOM 1680 ODl ASP B 5 38 .347 22 .794 -0 .039 1, .00 63 .04 8

ATOM 1681 OD2 ASP B 5 37 .430 20 .839 0 .374 1, .00 61 .10 8

ATOM 1682 C ASP B 5 35 .699 24 .381 3. .051 1. .00 51, .17 6

ATOM 1683 O ASP B 5 35 .179 25 .428 2 .670 1. .00 51 .32 8

ATOM 1684 N ILE B 6 35 .292 23 .713 4 .130 1, .00 49 .73 7

ATOM 1685 CA ILE B 6 34 .164 24 .178 4 .926 1. ,00 50 .09 6

ATOM 1686 CB ILE B 6 33 .723 23 .128 5 .950 1 .00 51 .11 6

ATOM 1687 CG2 ILE B 6 32 .472 23 .610 6 .678 1, .00 48 .60 6

ATOM 1688 CGI ILE B 6 33 .434 21 .809 5 .232 1. .00 53 .13 6

ATOM 1689 CDl ILE B 6 32 .881 20 .712 6 .121 1, .00 55 .06 6

ATOM 1690 C ILE B 6 34 .448 25 .480 5 .653 1, .00 49 .98 6

ATOM 1691 O ILE B- 6 33 .700 26 .450 5 .518 1 .00 51 .60 8

ATOM 1692 N LEU B 7 35 .524 25 .504 6 .426 1, .00 49 .48 7

ATOM 1693 CA LEU B 7 35 .908 26 .705 7 .160 1 .00 48 .15 6

ATOM 1694 CB LEU B 7 37 .157 26 .424 7. .995 1 .00 45 .60 6

ATOM 1695 CG LEU B 7 36 .916 25 .427 9 .126 1 .00 45 .98 6

ATOM 1696 CDl LEU B 7 38 .221 24 .935 9 .696 1 .00 46 .59 6

ATOM 1697 CD2 LEU B 7 36 .081 26 .086 10 .191 1 .00 44 .50 6 ATOM 1698 C LEU B 7 36.,167 27.,850 6,,195 1.00 47.,43 6

ATOM 1699 O LEU B 7 35. 797 28. 986 6. ,447 1. 00 46. 94 8

ATOM 1700 N TYR B 8 36. ,799 27. ,529 5. ,080 1. 00 49. ,45 7

ATOM 1701 CA TYR B 8 37. 105 28. 507 4. ,051 1. 00 52. ,16 6

ATOM 1702 CB TYR B 8 37. 800 27. 821 2. ,877 1. 00 54. ,75 6

ATOM 1703 CG TYR B 8 38. ,090 28. .758 1, .737 1. 00 56. ,10 6

ATOM 1704 CDl TYR B 8 39. 088 29. 720 1. ,839 1. 00 56. 48 6

ATOM 1705 CEl TYR B 8 39, .344 30. .605 0, .794 1. ,00 57. ,35 6

ATOM 1706 CD2 TYR B 8 37. 348 28. .701 0. .564 1. 00 57. ,26 6

ATOM 1707 CE2 TYR B 8 37. .592 29, ,581 -0. .484 1. 00 57. ,99 6

ATOM 1708 CZ TYR B 8 38. ,590 30. ,528 -0, .364 1. 00 57. ,33 6

ATOM 1709 OH TYR B 8 38. ,819 31. ,385 -1. .408 1. 00 58. ,94 8

ATOM 1710 C TYR B 8 35. .858 29. .234 3, .537 1. ,00 52, .55 6

ATOM 1711 O TYR B 8 35. ,867 30. ,460 3. ,387 1. 00 52, ,22 8

ATOM 1712 N ASN B 9 34, .796 28, .482 3 .249 1. ,00 52, ,51 7

ATOM 1713 CA ASN B 9 33. ,566 29. ,086 2. .752 1. 00 54. .09 6

ATOM 1714 CB ASN B 9 32 .539 28, .021 2. .376 1. ,00 56. .72 6

ATOM 1715 CG ASN B 9 32. ,963 27. ,203 1, .163 1. ,00 60, ,46 6

ATOM 1716 ODl ASN B 9 33. ,966 27. ,509 0. .512 1. 00 61. .72 8

ATOM 1717 ND2 ASN B 9 32, .198 26. .159 0, .852 1. ,00 61, .67 7

ATOM 1718 C ASN B 9 32. .980 30. .007 3. .794 1. ,00 54. .24 6

ATOM 1719 O ASN B 9 32 .680 31 .160 3 .506 1. .00 54 .66 8

ATOM 1720 N ILE B 10 32, .829 29. .503 5, .013 1. .00 54, .21 7

ATOM 1721 CA ILE B 10 32 .282 30 .310 6 .104 1. .00 53 .77 6

ATOM 1722 CB ILE B 10 32, .303 29, .543 7, .429 1. .00 52, .00 6

ATOM 1723 CG2 ILE B 10 31. .860 30. ,451 8. .552 1. ,00 50. ,79 6

ATOM 1724 CGI ILE B 10 31. .389 28, .323 7 .339 1. .00 50, .43 6

ATOM 1725 CDl ILE B 10 31, .531 27, .371 8, .498 1. .00 47, .56 6

ATOM 1726 C ILE B 10 33 .085 31 .592 6 .284 1 .00 55 .12 6

ATOM 1727 O ILE B 10 32, ,531 32, .663 6 .458 1. .00 56, .17 8

ATOM 1728 N ARG B 11 34 .400 31 .464 6. .243 1. .00 56, .91 7

ATOM 1729 CA ARG B 11 35 .297 32 .595 6 .386 1, .00 58 .48 6

ATOM 1730 CB ARG B 11 36. .739 32. ,110 6, .243 1, .00 63. .85 6

ATOM 1731 CG ARG B 11 37 .799 33 .170 6. .434 1, .00 68 .86 6

ATOM 1732 CD ARG B 11 37 .917 33. .493 7 .917 1. .00 77 .74 6

ATOM 1733 NE ARG B 11 3 .211 34 .078 8 .264 1, .00 85 .52 7

ATOM 1734 CZ ARG B 11 40 .384 33 .635 7 .807 1, .00 88 .55 6

ATOM 1735 NHl ARG B 11 40 .424 32 .589 6 .970 1. .00 90, .95 7

ATOM 1736 NH2 ARG B 11 41 .518 34 .239 8 .178 1, .00 87 .63 7

ATOM 1737 C ARG B 11 35, .030 33, .639 5, .306 1, .00 58, .49 6

ATOM 1738 O ARG B 11 34 .905 34 .825 5 .584 1, .00 57 .34 8

ATOM 1739 N GLN B 12 34, .933 33, .175 4, .066 1. .00 58, .50 7

ATOM 1740 CA GLN B 12 34 .748 34 .055 2 .927 1 .00 57 .77 6

ATOM 1741 CB GLN B 12 35 .147 33 .329 1 .653 1. .00 58 .35 6

ATOM 1742 CG GLN B 12 36 .124 34 .100 0 .814 1 .00 62 .22 6

ATOM 1743 CD GLN B 12 37 .514 33 .973 1 .351 1. .00 64 .08 6

ATOM 1744 OEl GLN B 12 38 .011 32 .862 1 .501 1 .00 68 .35 8

ATOM 1745 NE2 GLN B 12 38 .156 35 .098 1 .653 1 .00 63 .78 7

ATOM 1746 C GLN B 12 33, .366 34 .633 2. .720 1. .00 57 .86 6

ATOM 1747 O GLN B 12 33 .219 35 .657 2 .059 1 .00 59 .62 8

ATOM 1748 N THR B 13 32 .345 33 .994 3 .266 1 .00 57 .21 7

ATOM 1749 CA THR B 13 30 .987 34 .479 3 .054 1 .00 56 .88 6

ATOM 1750 CB THR B 13 30 .101 33 .373 2 .468 1 .00 54 .90 6

ATOM 1751 OG1 THR B 13 30 .100 32 .247 3 .350 1 .00 55 .07 8

ATOM 1752 CG2 THR B 13 30 .612 32 .946 1 .104 1 .00 56 .83 6

ATOM 1753 C THR B 13 30 .295 35 .009 4 .298 1 .00 58 .52 6

ATOM 1754 O THR B 13 29 .275 35 .698 4 .206 1 .00 57 .64 8

ATOM 1755 N SER B 14 30 .848 34 .691 5 .462 1 .00 60 .24 7

ATOM 1756 CA SER B 14 30 .247 35 .117 6 .715 1 .00 60 .31 6

ATOM 1757 CB SER B 14 30 .884 34 .369 7 .878 1 .00 60 .50 6

ATOM 1758 OG SER B 14 30 .086 34 .485 9 .034 1 .00 63 .18 8 ATOM 1759 C SER B 14 30.343 36.619 6.949 1.00 59.80 6

ATOM 1760 O SER B 14 31. 247 37. 293 6. 443 1. 00 60. 23 8

ATOM 1761 N ARG B 15 29. 382 37. ,134 7. ,710 1. ,00 58. ,15 7

ATOM 1762 CA ARG B 15 29. 322 38. ,549 8. ,040 1. 00 55. ,80 6

ATOM 1763 CB ARG B 15 28. 271 39. 239 7. ,183 1. 00 56. 87 6

ATOM 1764 CG ARG B 15 28. 540 39. 145 5. ,684 1. 00 60. ,72 , 6

ATOM 1765 CD ARG B 15 27. ,721 40. ,179 4. .945 1. ,00 63. ,19 6

ATOM 1766 NE ARG B 15 28. ,008 41. ,515 5. .475 1. ,00 67. ,21 7

ATOM 1767 CZ ARG B 15 27. 307 42. ,616 5. .196 1. 00 67. ,82 6

ATOM 1768 NHl ARG B 15 26. ,259 42. .549 4. .384 1. ,00 69. ,12 7

ATOM 1769 NH2 ARG B 15 27. ,660 43. .789 5. .722 1. ,00 66. .84 7

ATOM 1770 C ARG B 15 28. ,962 38. .655 9. .511 1. ,00 54. ,09 6

ATOM 1771 0 ARG B 15 27. 795 38. ,651 9. ,880 1. 00 55. ,59 8

ATOM 1772 N PRO B 16 29. ,979 38. ,747 10. .377 1. 00 51. ,42 7

ATOM 1773 CD PRO B 16 31. ,405 38. ,751 10. .015 1. ,00 48. .17 6

ATOM 1774 CA PRO B 16 29. .817 38, ,846 11, .828 1. ,00 48. .94 6

ATOM 1775 CB PRO B 16 31. ,256 38. .950 12. .328 1. 00 48. .44 6

ATOM 1776 CG PRO B 16 32, ,038 38, .262 11. .284 1. ,00 48. .62 6

ATOM 1777 C PRO B 16 28, ,974 40. ,014 12. ,300 1. 00 48. ,35 6

ATOM 1778 O PRO B 16 28. ,475 40. .006 13, .420 1. ,00 49, .87 8

ATOM 1779 N ASP B 17 28. ,825 41. ,026 11. .456 1. ,00 49. ,55 7

ATOM 1780 CA ASP B 17 28, ,048 42. .201 11. .830 1. ,00 51. .87 6

ATOM 1781 CB ASP B 17 28. .638 43. .469 11. .204 1. ,00 55. .73 6

ATOM 1782 CG ASP B 17 29, .956 43, .896 11 .856 1, .00 59, .93 6

ATOM 1783 ODl ASP B 17 30, .158 43, .598 13, .062 1. .00 60, .57 8

ATOM 1784 OD2 ASP B 17 30. .781 44. .548 11. ,163 1, ,00 61. .01 8

ATOM 1785 C ASP B 17 26. .581 42. .120 11, .458 1, .00 51. ,65 6

ATOM 1786 O ASP B 17 25, .837 43, .066 11, .684 1. .00 51, .12 8

ATOM 1787 N VAL B 18 ^'26, .156 40, .990 10 .906 1, ,00 53 .24 7

ATOM 1788 CA VAL B 18 24, .772 40, .848 10, .495 1. ,00 53. .38 6

ATOM 1789 CB VAL B 18 24, .679 40, .682 8 .978 1. ,00 52 .53 6

ATOM 1790 CGI VAL B 18 23, .238 40 .628 8 .551 1, .00 53 .33 6

ATOM 1791 CG2 VAL B 18 25, .385 41, .833 8, .299 1. . 00 52, .08 6

ATOM 1792 C VAL B 18 24, .026 39, .701 11. .157 1, .00 54 .80 6

ATOM 1793 O VAL B 18 24, .359 38. .527 10. .980 1. .00 57, .05 8

ATOM 1794 N ILE B 19 22 .999 40 .062 11 .913 1, .00 55 .38 7

ATOM 1795 CA ILE B 19 22 .150 39 .105 12 .615 1, .00 54 .84 6

ATOM 1796 CB ILE B 19 21 .128 39 .899 13 .493 1, .00 53 .97 6

ATOM 1797 CG2 ILE B 19 20 .177 40 .699 12 .612 1 .00 52 .99 6

ATOM 1798 CGI ILE B 19 20 .354 38 .963 14 .414 1, .00 54 .58 6

ATOM 1799 CDl ILE B 19 19 .598 39 .696 15 .490 1 .00 51 .38 6

ATOM 1800 C ILE B 19 21 .450 38 .192 11 .586 1 .00 55 .77 6

ATOM 1801 O ILE B 19 20 .879 38 .678 10 .605 1 .00 56 .23 8

ATOM 1802 N PRO B 20 21 .508 36 .857 11 .787 1 .00 57 .54 7

ATOM 1803 CD PRO B 20 22 .223 36 .204 12 .888 1 .00 57 .31 6

ATOM 1804 CA PRO B 20 20 .900 35 .841 10 .900 1 .00 59 .26 6

ATOM 1805 CB PRO B 20 21 .478 34 .521 11 .417 1 .00 57 .46 6

ATOM 1806 CG PRO B 20 22 .657 34 .935 12 .235 1 .00 58 .77 6

ATOM 1807 C PRO B 20 19 .366 35 .836 10 .940 1 .00 62 .02 6

ATOM 1808 O PRO B 20 18 .732 34 .806 11 .185 1 .00 61 .74 8

ATOM 1809 N THR B 21 18 .781 36 .997 10 .679 1 .00 65 .81 7

ATOM 1810 CA THR B 21 17 .337 37 .160 10 .705 1 .00 69 .72 6

ATOM 1811 CB THR B 21 16 .974 38 .658 10 .971 1 .00 67 .96 6

ATOM 1812 OG1 THR B 21 16 .710 38 .837 12 .367 1 .00 69 .51 8

ATOM 1813 CG2 THR B 21 15 .765 39 .087 10 .178 1 .00 68 .09 6

ATOM 1814 C THR B 21 16 .606 36 .658 9 .455 1 .00 73 .11 6

ATOM 1815 O THR B 21 17 .000 36 .942 8 .315 1 .00 71 .83 8

ATOM 1816 N GLN B 22 15 .532 35 .907 9 .694 1 .00 77 .49 7

ATOM 1817 CA GLN B 22 14 .684 35 .370 8 .629 1 .00 80 .52 6

ATOM 1818 CB GLN B 22 14 .492 33 .871 8 .842 1 .00 81 .72 6

ATOM 1819 CG GLN B 22 15 .793 33 .097 8 .917 1 .00 83 .16 6 ATOM 1820 CD GLN B 22 15.654 31.832 99..775533 ,00 85.69

ATOM 1821 OEl GLN B 22 15.421 31.901 1100..997766 00 08

ATOM 1822 NE2 GLN B 22 15.787 30.665 99..110033 00 85 7

ATOM 1823 C GLN B 22 13.326 36.091 88..771177 1. ,00 81. ,72 6

ATOM 1824 O GLN B 22 12.526 35.837 99..663322 1. ,00 80. ,46 8

ATOM 1825 N ARG B 23 13.075 36.990 77..776655 1. .00 84. .00 7

ATOM 1826 CA ARG B 23 11.829 37.769 7.744 1. ,00 86. ,23 6

ATOM 1827 CB ARG B 23 10.599 36.840 7.695 1. .00 87. .50 6

ATOM 1828 CG ARG B 23 10.348 36.215 6,.314 1. .00 89. .89 6

ATOM 1829 CD ARG B 23 10.796 34.734 6..215 1. .00 90. .83 6

ATOM 1830 NE ARG B 23 10.694 34.242 4.833 1. .00 93. ,76 7

ATOM 1831 CZ ARG B 23 9.590 34.302 4.068 1. .00 95, ,64 6

ATOM 1832 NHl ARG B 23 8.452 34.832 4.534 1. . .0000 9966.. .1177 7

ATOM 1833 NH2 ARG B 23 9.627 33.855 2.811 1. . ,0000 9955.. .0033 7

ATOM 1834 C ARG B 23 11.754 38.657 8.987 1. ..0000 8866. .0033 6

ATOM 1835 O ARG B 23 12.776 39.137 9.476 1. .00 85. .87

ATOM 1836 N ASP B 24 10.548 38.879 9.497 1. .00 86 .08 7

ATOM 1837 CA ASP B 24 10.393 39.703 10.693 1. .00 85, .72 6

ATOM 1838 CB ASP B 24 8.975 40.301 10.799 1. .00 89. .17 6

ATOM 1839 CG ASP B 24 8.226 40.339 9.453 1, .00 90, .77 6

ATOM 1840 ODl ASP B 24 8.743 40.965 8.486 ,00 92.05

ATOM 1841 OD2 ASP B 24 7.113 39.746 9.376 .00 89.95

ATOM 1842 C ASP B 24 10.622 38.798 11.891 .00 83.93

ATOM 1843 O ASP B 24 10.445 39.218 13.045 1.00 83.66

ATOM 1844 N ARG B 25 10.994 37.549 11.613 1.00 81.18 7

ATOM 1845 CA ARG B 25 11.237 36.584 12.677 1.00 78.99 6

ATOM 1846 CB ARG B 25 11.318 35.159 12.128 1.00 82.30 6

ATOM 1847 CG ARG B 25 10.001 34.541 11.696 1.00 87.15 6

ATOM 1848 CD ARG B 25 10.171 33.024 11.485 1.00 91.09 6

ATOM 1849 NE ARG B 25 8.908 32.371 11.140 .00 95.87 7

ATOM 1850 CZ ARG B 25 8.747 31.053 11.005 .00 98.43 6

ATOM 1851 NHl ARG B 25 9.785 30.235 11.186 .00 97.96 7

ATOM 1852 NH2 ARG B 25 7.538 30.549 10.709 .00 99.56 7

ATOM 1853 C ARG B 25 12.527 36.876 13.426 ,00 75.18 6

ATOM 1854 O ARG B 25 13.573 37.105 12.813 .00 75.11 8

ATOM 1855 N PRO B 26 12.463 36.879 14.767 .00 71.32 7

ATOM 1856 CD PRO B 26 11.233 36.885 15.569 .00 69 .54 6

ATOM 1857 CA PRO B 26 13.629 37.134 15.617 00 68.20

ATOM 1858 CB PRO B 26 13.020 37.298 17.007 00 68.04

ATOM 1859 CG PRO B 26 11.627 37.763 16.720 1.00 68.94

ATOM 1860 C PRO B 26 14.543 35.917 15.572 1.00 65.66

ATOM 1861 O PRO B 26 14.114 34.832 15.183 1.00 65.23 8

ATOM 1862 N VAL B 27 15.801 36.093 15.956 1.00 62.13 7

ATOM 1863 CA VAL B 27 16.716 34.969 15.990 1.00 58.35 6

ATOM 1864 CB VAL B 27 18.185 35.416 15.851 1.00 57.74 6

ATOM 1865 CGI VAL B 27 19.127 34.308 16.328 1.00 54.93 6

ATOM 1866 CG2 VAL B 27 18.479 35.737 14.393 1.00 54.94 6

ATOM 1867 C VAL B 27 16.491 34.348 17.349 1.00 56.29 6

ATOM 1868 O VAL B 27 16.517 35.043 18.360 1.00 56.31 8

ATOM 1869 N ALA B 28 16.243 33.045 17.379 1.00 54.44 7

ATOM 1870 CA ALA B 28 16.008 32.384 18.645 1.00 52.98 6

ATOM 1871 CB ALA B 28 15.095 31.209 18.461 1.00 52.15 6

ATOM 1872 C ALA B 28 •17.318 31.938 19.262 1.00 52.73 6

ATOM 1873 O ALA B 28 17.959 31.004 18.782 1.00 51.86 8

ATOM 1874 N VAL B 29 17.696 32.632 2200..333344 1.00 51.10 7

ATOM 1875 CA VAL B 29 18.911 32.353 2211..008800 1.00 49.08 6

ATOM 1876 CB VAL B 29 19.741 33.642 2211..332244 00 49.72 6

ATOM 1877 CGI VAL B 29 20.986 33.323 2222..114400 00 46.43

ATOM 1878 CG2 VAL B 29 20.117 34.272 1199..999966 1.00 49.12

ATOM 1879 C VAL B 29 18.553 31.762 2222..442288 1.00 48.65

ATOM 1880 O VAL B 29 17.731 32.301 23.161 1.00 48.71 -ilIΛ_>

ATOM 1881 N SER B 30 19. 169 30. ,638 22. ,746 1. 00 50. 09 7

ATOM 1882 CA SER B 30 18. 925 29. 997 24. 018 1. 00 53. 68 6

ATOM 1883 CB SER B 30 18. 587 28. ,521 23. 817 1. 00 53. ,36 6

ATOM 1884 OG SER B 30 19. ,653 27. ,845 23. ,180 1. 00 57. ,88 8

ATOM 1885 C SER B 30 20. ,201 30. ,150 24. ,823 1. 00 56. ,00 6

ATOM 1886 O SER B 30 21. ,297 29. ,933 24. .306 1. 00 57. ,56 8

ATOM 1887 N VAL B 31 20. .049 30. .542 26, .084 1. ,00 57. ,69 7

ATOM 1888 CA VAL B 31 21, .175 30. .752 26, .980 1. ,00 57. .19 6

ATOM 1889 CB VAL B 31 21. ,227 32. ,198 27. .460 1. 00 57. ,32 6

ATOM 1890 CGI VAL B 31 22. .536 32. .449 28. ,185 1. 00 .58. ,47 6

ATOM 1891 CG2 VAL B 31 21, ,044 33. .147 26. .288 1. ,00 56. ,64 6

ATOM 1892 C VAL B 31 21. ,016 29. ,878 28. .204 1. 00 57. 98 6

ATOM 1893 O VAL B 31 19. .938 29, .815 28, .787 1. ,00 59. ,53 8

ATOM 1894 N SER B 32 22. .101 29, .232 28, .611 1. ,00 58. .26 7

ATOM 1895 CA SER B 32 22, .069 28, .356 29, .765 1. ,00 58, .30 6

ATOM 1896 CB SER B 32 21. .806 26. .914 29, .298 1. ,00 60. ,26 6

ATOM 1897 OG SER B 32 21, .881 25 .975 30, .361 1. ,00 61, ,39 8

ATOM 1898 C SER B 32 23. ,374 28. .414 30, ,530 1. ,00 58, ,22 6

ATOM 1899 O SER B 32 24, ,402 27, ,983 30, .024 1. ,00 62. .28 8

ATOM 1900 N LEU B 33 23, .340 28, .937 31 .753 1. ,00 56, .90 7

ATOM 1901 CA LEU B 33 24. .548 29. .002 32, .572 1. ,00 56, .09 6

ATOM 1902 CB LEU B 33 24, .489 30. ,183 33, .541 1, ,00 54, ,84 6

ATOM 1903 CG LEU B 33 24, ,257 31. .555 32. .914 1. .00 55, ,33 6

ATOM 1904 CDl LEU B 33 2 .483 32 .647 33 .962 1. .00 53. .97 6

ATOM 1905 CD2 LEU B 33 25, .201 31, .731 31 .737 1. .00 56. .27 6

ATOM 1906 C LEU B 33 24. .725 27. .728 33, ,379 1. ,00 55. ,50 6

ATOM 1907 O LEU B 33 23. .770 27, .220 33, .950 1. .00 56. .54 8

ATOM 1908 N LYS B 34 25. .948 27, .215 33, .413 1. .00 55. .65 7

ATOM 1909 CA LYS B 34 26. .270 26, .018 34, .183 1. .00 56. .27 6

ATOM 1910 CB LYS B 34 26, .815 24, .905 33, .279 1. ,00 60. .64 6

ATOM 1911 CG LYS B 34 25 .908 24, .528 32, .102 1. .00 66, ,07 6

ATOM 1912 CD LYS B 34 24 .552 23 .965 32 .566 1. .00 72, .18 6

ATOM 1913 CE LYS B 34 23 .611 23 .670 31 .373 1. .00 74, .46 6

ATOM 1914 NZ LYS B 34 22 .303 23. .068 31 .799 1. .00 74, .04 7

ATOM 1915 C LYS B 34 27, .365 26, .493 35, .108 1. ,00 54. ,54 6

ATOM 1916 O LYS B 34 28 .463 26 .811 34 .655 1 .00 55 .93 8

ATOM 1917 N PHE B 35 27 .079 26 .564 36 .401 1. ,00 52, .21 7

ATOM 1918 CA HE^' B 35 28 .086 27 .045 37 .336 1. ,00 49, ,54 6

ATOM 1919 CB PHE B 35 27 .422 27, .491 38 .633 1, .00 46, .23 6

ATOM 1920 CG PHE B 35 26 .545 28 .682 38 .450 1. .00 47, .55 6

ATOM 1921 CDl PHE B 35 25 .230 28 .536 38 .035 1, .00 48 .89 6

ATOM 1922 CD2 PHE B 35 27 .056 29 .968 38 .603 1, .00 48, .56 6

ATOM 1923 CEl PHE B 35 24 .434 29 .653 37 .771 1 .00 47 .34 6

ATOM 1924 CE2 PHE B 35 26 .269 31 .087 38 .343 1. .00 45 .87 6

ATOM 1925 CZ PHE B 35 24 .958 30 .927 37 .926 1. .00 47, .81 6

ATOM 1926 C PHE B 35 29 .224 26 .072 37 .595 1 .00 49 .37 6

ATOM 1927 O PHE B 35 29, .020 24, .880 37 .833 1, .00 48, .82 8

ATOM 1928 N ILE B 36 30 .434 26 .609 37 .530 1 .00 47 .17 7

ATOM 1929 CA ILE B 36 31 .634 25 .820 37 .706 1 .00 45 .02 6

ATOM 1930 CB ILE B 36 32 .641 26 .106 36 .574 1 .00 42 .09 6

ATOM 1931 CG2 ILE B 36 33 .858 25, .230 36, .717 1. .00 38, .48 6

ATOM 1932 CGI ILE B 36 31 .966 25 .897 35 .224 1. .00 41, .05 6

ATOM 1933 CDl ILE B 36 •31 .393 24 .520 35 .028 1 .00 41 .45 6

ATOM 1934 C ILE B 36 32 .284 26 .141 39 .029 1, .00 45 .51 6

ATOM 1935 O ILE B 36 32 .977 25 .304 39 .603 1, .00 45 .83 8

ATOM 1936 N ASN B 37 32 .068 27 .351 39 .522 1 .00 45 .06 7

ATOM 1937 CA ASN B 37 32 .678 27 .719 40 .792 1 .00 45 .81 6

ATOM 1938 CB ASN B 37 34 .200 27 .712 40 .652 1 .00 43 .65 6

ATOM 1939 CG ASN B 37 34 .900 27 .384 41 .950 1 .00 47 .86 6

ATOM 1940 ODl ASN B 37 34 .518 27 .864 43 .025 1, .00 49 .43 8

ATOM 1941 ND2 ASN B 37 35 .942 26 .572 41 .862 1 .00 46 .99 7 ATOM 1942 C ASN B 37 32..222 29,.077 41..322 1,,00 45.,58 6

ATOM 1943 O ASN B 37 31. ,767 29. .931 40. ,566 1. ,00 44. ,62 8

ATOM 1944 N ILE B 38 32. ,335 29, .248 42. .635 1. ,00 45. .83 7

ATOM 1945 CA ILE B 38 31. ,973 30, .489 43. .301 1. .00 47. .98 6

ATOM 1946 CB ILE B 38 30. ,781 30. ,287 44. ,214 1. ,00 46. .41 6

ATOM 1947 CG2 ILE B 38 30. .510 31, .550 44, .976 1. .00 46, .45 6

ATOM 1948 CGI ILE B 38 29. .567 29, .905 43. .356 1. .00 47. .23 6

ATOM 1949 CDl ILE B 38 28. .365 29. .406 44. .105 1. ,00 48. .96 6

ATOM 1950 C ILE B 38 33. .221 30, .805 44, .086 1. .00 50. .65 6

ATOM 1951 O ILE B 38 33. ,546 30, .109 45, .040 1. .00 52. .37 8

ATOM 1952 N LEU B 39 33, .926 31 .855 43, .668 1. .00 52, .96 7

ATOM 1953 CA LEU B 39 35. ,207 32, .214 44, ,264 1. .00 53. .68 6

ATOM 1954 CB LEU B 39 36. ,137 32, .698 43, .157 1. .00 53. .70 6

ATOM 1955 CG LEU B 39 36, .204 31, .706 42. .000 1. .00 53, .99 6

ATOM 1956 CDl LEU B 39 37. .099 32. .257 40. .904 1. .00 53. .07 6

ATOM 1957 CD2 LEU B 39 36. .718 30, .364 42. ,510 1. .00 51. .88 6

ATOM 1958 C LEU B 39 35, .272 33. .188 45, .418 1. .00 54 .85 6

ATOM 1959 O LEU B 39 36, .061 32, .994 46. ,342 1. .00 55. .07 8

ATOM 1960 N GLU B 40 34, .489 34, .255 45. ,359 1. .00 55. .18 7

ATOM 1961 CA GLU B 40 34, .509 35 .220 46. .446 1. .00 58, .32 6

ATOM 1962 CB GLU B 40 35. ,423 36. .400 46. ,144 1. ,00 59. .68 6

ATOM 1963 CG GLU B 40 36. .879 36, .041 46, ,018 1. .00 65 .11 6

ATOM 1964 CD GLU B 40 37, ,749 37, .271 45. ,846 1, .00 69, .72 6

ATOM 1965 OEl GLU B 40 37, ,534 38. .034 44, .867 1, .00 72 .04 8

ATOM 1966 OE2 GLU B 40 38. .648 37, .477 46, .693 1. .00 70, .63 8

ATOM 1967 C GLU B 40 33. .128 35. .738 46, ,685 1. .00 59 .54 6

ATOM 1968 O GLU B 40 32 .393 36 .057 45, ,747 1, .00 59 .65 8

ATOM 1969 N VAL B 41 32. .772 35. .816 47. .956 1. .00 60, .26 7

ATOM 1970 CA VAL B 41 31 .468 36 .304 48, ,323 1, .00 58 .68 6

ATOM 1971 CB VAL B 41 30. .599 35, .159 48, ,862 1, .00 59, .00 6

ATOM 1972 CGI VAL B 41 29. .318 35, .711 49, .450 1. .00 61, .18 6

ATOM 1973 CG2 VAL B 41 30. .279 34. .186 47. ,740 1. .00 59. .58 6

ATOM 1974 C VAL B 41 31, .666 37. .368 49, .379 1. .00 58, .15 6

ATOM 1975 O VAL B 41 32, .594 37, .290 50. .187 1, .00 56, .97 8

ATOM 1976 N ASN B 42 30, .811 38, .383 49. .337 1. .00 58, .17 7

ATOM 1977 CA ASN B 42 30, .863 39, .466 50, .302 1, .00 58, .74 6

ATOM 1978 CB ASN B 42 31, .609 40 .673 49, .730 1, .00 58 .84 6

ATOM 1979 CG ASN B 42 31. .962 41 .702 50, .795 1, .00 58 .68 6

ATOM 1980 ODl ASN B 42 31. .122 42 .100 51. .593 1. .00 58 .91 8

ATOM 1981 ND2 ASN B 42 33 .215 42 .138 50, .806 1. .00 58 .72 7

ATOM 1982 C ASN B 42 29, .412 39, .823 50. .577 1, .00 60 .60 6

ATOM 1983 O ASN B 42 28, .738 40 .457 49, .747 1, .00 60 .01 8

ATOM 1984 N GLU B 43 28 .926 39 .401 51, .742 1 .00 61 .86 7

ATOM 1985 CA GLU B 43 27. .543 39, .669 52. ,111 1. .00 62, .81 6

ATOM 1986 CB GLU B 43 27 .117 38 .760 53 .267 1 .00 64 .87 6

ATOM 1987 CG GLU B 43 25 .640 38 .871 53, .591 1. .00 67 .01 6

ATOM 1988 CD GLU B 43 25, .152 37 .779 54, .525 1. .00 69 .52 6

ATOM 1989 OEl GLU B 43 23 .973 37 .842 54 .945 1. .00 68 .10 8

ATOM 1990 OE2 GLU B 43 25 .944 36 .854 54 .831 1 .00 70 .46 8

ATOM 1991 C GLU B 43 27 .332 41 .132 52 .476 1 .00 60 .60 6

ATOM 1992 O GLU B 43 26 .223 41 .649 52, .387 1 .00 59 .23 8

ATOM 1993 N ILE B 44 28 .408 41 .792 52, .882 1 .00 60 .18 7

ATOM 1994 CA ILE B 44 28 .356 43 .199 53 .254 1 .00 61 .54 6

ATOM 1995 CB ILE B 44 29 .674 43 .669 53, .910 1, .00 62 .98 6

ATOM 1996 CG2 ILE B 44 29 .601 45 .172 54, .183 1, .00 61 .14 6

ATOM 1997 CGI ILE B 44 29 .950 42 .877 55 .194 1 .00 63 .64 6

ATOM 1998 CDl ILE B 44 29 .004 43 .205 56 .335 1 .00 65 .05 6

ATOM 1999 C ILE B 44 28 .141 44 .069 52 .016 1 .00 62 .14 6

ATOM 2000 O ILE B 44 27 .318 44 .992 52 .024 1 .00 62 .54 8

ATOM 2001 N THR B 45 28 .894 43 .773 50 .959 1 .00 60 .63 7

ATOM 2002 CA THR B 45 28 .806 44 .527 49, .721 1. .00 59 .11 6 en en 4^ oo oo IV) ro o en o en o en o en o en en ^ _.μ : ' :)' ;y ;-s ' ^ ' >' to ;»' ;-w i__ ^ι ^ βμ3 ^£3 Ha ^μ3.^ ,^ .β βββ β β β βββ^ 3βββ β >^ H3ιβ ^ β ^ β ^ 3 β β β>^ 3!^ ^ ι-3 β β ι^ ^ β O OO OO O O O O O OOOOO O OO OO OO O O O O OO O O O OO O O O O O Q O O O Q QQ QQOOQ QQO QO Q O O Q O gggggggggggggggggggggggggggggggggggggggggggSSgggggggggggggSg

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o t t t M t t>o t ω ω LΛ j ω J ω LJ ω ω -NJ _o L ω ω ω o oo sθ co o _o oo co o μ-^Λ μ^> n ι!-. __i M W bJ t s_o ι_D o -¹ W M to m Lπ π j_i _^ tsJ ω ω μ^j ι_o o -J --J Ln tsJ π o μ-» ts o ^ o Λ ∞ Lo --J io N-> ω -J o v_^ tl-> > ^ t\_. μ^ σ. u__ -NJ ω w Lπ tj o ^j . u_> cr_ υ ) co cr. .p- co ι n .j-> θD -j π to c_n ι_π _ Lπ ι^ Lπ co oo -j Lπ σϊ Co μ-> o .)^ co μ-^» » w μ^j o M U_> CΛ tJ o

Lu ω ⁾ Lo ω u_i Lυ o U⁾ L L L _. J > (__ ^ ω .ι^ u) d-> ._^ >[^ .t^ Lθ Lυ ^ t Lπ ω ^ .i-> ^ uι .^ σ^ . σΛ - ι CD _ oo o ∞ o so o W o R M W .^ bθ W π Lπ μ^j θ L sD -j tNj ω Lπ --o o μ^j Lo -J Lπ o oo o i£> ^ Lπ n ₁^ ιf^ Lπ so M_) -J μ-¹ __n σ _\_> ι>J θo tø u_. o --o μ-^Λ cn ij ω μ-ⁱ μ^j ∞ Lπ ι_o o o o co .^j c s£> ω

-J t-' tθ H' L oo ι^ ω co i-π oo co oo Lo oι ω oo oo σι ι o _o σι ^ vD ω n ιi^ π o -J μ^j μ-> .-> μ^j μⁱ μ^j μ-> μ-^ι .-> μ-ⁱ H^ι μ-^ι μ-^ι μ^j μ^j H μ^j μ-' H' -' -> μ-^ι (-¹ H' μ-^l μ-' μ-' h-^ι μ-> μ-^ι μ-' μ-^ι μ-' μ-¹ μ-> μ-¹ μ-> H¹ P P P P μ μ μ ooooσσoooooσoooo oσoooooooooσoooooooooooooσooσoooooooooooooo aoooσ ooooσoσoooooo σooσ oo σoo cno ooσσoooooooooooooσooooo ooooo

)_-> μ^ ι^ ^ ^ ιl^ ^ ιl-> ^ ^ αi ιfi _^ ^ y^ ^ ^ ^ ι π ιC- ιjι ^ ^ ιfi ^ n uι υι ui ι^ >^ u^ w u u u u w w p p w ∞ ij o o ω _^ uι α) J _ -j o ω iD ω ιi⁾ P M o P io co o ω o ω ιo o o o o m p iJ p ω p u to ^ oι uι m ^ w ι ffl co <ιι o c

_t^ ro ω ∞ μ^j θΛ ω -j fcj __π w o ∞ __^ --j μ-' -J π s_o θ ω so m ω c c^ ^ ) ι _o u μ tJ ^ μ ιB μ ^o μ (D (Λ ω ^ ^o ω α) l_] p co _o ι ^Jl (Λ P ιs ol fc ω o (Λ P ^J (Λ (» ^■J U M l ^ p ^ o^ l ώ a lJ m cn _i ^ ϋl o ι p Λ Λ (Λ _Λ m n σι tn __ι ι m σι m

ATOM 2064 O PHE B 52 31..264 30.,008 32..585 1..00 46.,26 8

ATOM 2065 N TRP B 53 29. ,692 28. ,428 32. .655 1. 00 44. ,90 7

ATOM 2066 CA TRP B 53 29, .725 28, ,188 31. ,223 1. ,00 47. ,46 6

ATOM 2067 CB TRP B 53 29. .655 26. ,698 30. ,907 1. ,00 47. ,31 6

ATOM 2068 CG TRP B 53 30. ,869 25. ,949 31. ,278 1. 00 49. ,36 6

ATOM 2069 CD2 TRP B 53 31. ,029 24. 535 31. ,246 1. 00 50. 82 6

ATOM 2070 CE2 TRP B 53 32. ,342 24. ,253 31. ,686 1. ,00 49. ,80 6

ATOM 2071 CE3 TRP B 53 30. .189 23, .473 30, .887 1. .00 51. ,30 6

ATOM 2072 CDl TRP B 53 32. .057 26. .463 31. .719 1. .00 50. .05 6

ATOM 2073 NEl TRP B 53 32. .947 25. ,448 31. .968 1. ,00 50. .43 7

ATOM 2074 CZ2 TRP B 53 32. .835 22, ,955 31. .779 1. ,00 50. .23 6

ATOM 2075 CZ3 TRP B 53 30. .676 22. .182 30. ,977 1. .00 49. .78 6

ATOM 2076 CH2 TRP B 53 31. .990 21. .932 31. ,421 1. ,00 50. ,88 6

ATOM 2077 C TRP B 53 28. .516 28. ,860 30. ,619 1. 00 48. ,93 6

ATOM 2078 O TRP B 53 27. ,388 28, .490 30, .912 1. .00 48, .69 8

ATOM 2079 N GLN B 54 28. .746 29 .846 29, .770 1. .00 50, .46 7

ATOM 2080 CA GLN B 54 27, .643 30, .543 29, .155 1. .00 51, .66 6

ATOM 2081 CB GLN B 54 28. ,036 31. .984 28, .844 1. ,00 51, .35 6

ATOM 2082 CG GLN B 54 26. .871 32. ,851 28. .407 1. ,00 53, .49 6

ATOM 2083 CD GLN B 54 27. ,117 34, ,326 28, .693 1. .00 57. .50 6

ATOM 2084 OEl GLN B 54 27. ,399 34. ,711 29. ,837 1. ,00 57. .95 8

ATOM 2085 NE2 GLN B 54 27, .016 35, .161 27. .659 1. ,00 58, .04 7

ATOM 2086 C GLN B 54 27, .273 29, ,790 27, .898 1. .00 52, .38 6

ATOM 2087 0 GLN B 54 27. .564 30. .209 26. ,786 1. .00 54. .42 8

ATOM 2088 N GLN B 55 26, .638 28. .650 28. .101 1. .00 52, .78 7

ATOM 2089 CA GLN B 55 26. .203 27. .793 27, .017 1, ,00 53, .84 6

ATOM 2090 CB GLN B 55 25, ,672 26. .501 27. .623 1, ,00 58. ,14 6

ATOM 2091 CG GLN B 55 24. .985 25. .549 26. .663 1. ,00 66, .74 6

ATOM 2092 CD GLN B 55 24 .756 24 .190 27 .315 1. .00 70 .87 6

ATOM 2093 OEl GLN B 55 24 .456 24, .108 28 .528 1, .00 73 .46 8

ATOM 2094 NE2 GLN B 55 24, .897 23, .117 26, .527 1, .00 69, .32 7

ATOM 2095 C GLN B 55 25, .145 28, .495 26, .168 1. ,00 51, .37 6

ATOM 2096 O GLN B 55 23, .993 28, .631 26, .563 1. ,00 52 .24 8

ATOM 2097 N THR B 56 25, .558 28. .935 24, .989 1. ,00 48, .92 7

ATOM 2098 CA THR B 56 24, .690 29. .660 24. .083 1, .00 47. .03 6

ATOM 2099 CB THR B 56 25, .307 31, .018 23. .741 1. ,00 47, .18 6

ATOM 2100 OG1 THR B 56 25 .758 31, .647 24 .946 1. .00 46 .91 8

ATOM 2101 CG2 THR B 56 24 .291 31 .909 23 .056 1 .00 45 .50 6

ATOM 2102 C THR B 56 24 .466 28 .896 22 .787 1, .00 46 .66 6

ATOM 2103 O THR B 56 25, .351 28, .202 22. .306 1, ,00 46 .60 8

ATOM 2104 N THR B 57 23 .273 29 .034 22 .220 1, .00 45 .86 7

ATOM 2105 CA THR B 57 22, .942 28, .350 20, .984 1, .00 44 .53 6

ATOM 2106 CB THR B 57 22 .320 26 .958 21 .247 1 .00 44 .84 6

ATOM 2107 OG1 THR B 57 23 .271 26 .115 21 .910 1 .00 41 .11 8

ATOM 2108 CG2 THR B 57 21 .942 26 .306 19 .936 1, .00 46 .63 6

ATOM 2109 C THR B 57 21 .967 29 .152 20 .162 1 .00 43 .27 6

ATOM 2110 O THR B 57 21 .106 29 .825 20 .700 1 .00 44 .01 8

ATOM 2111 N TRP B 58 22 .122 29 .086 18 .849 1 .00 41 .40 7

ATOM 2112 CA TRP B 58 21, .235 29, .792 17, .945 1, .00 42 .18 6

ATOM 2113 CB TRP B 58 21 .500 31 .302 17 .968 1. .00 40 .63 6

ATOM 2114 CG TRP B 58 22 .800 31 .729 17 .377 1 .00 40 .64 6

ATOM 2115 CD2 TRP B 58 24 .048 31 .827 18 .054 1 .00 37 .47 6

ATOM 2116 CE2 TRP B 58 24 .998 32 .252 17 .113 1 .00 37 .44 6

ATOM 2117 CΞ3 TRP B 58 24 .456 31 .594 19 .371 1 .00 37 .69 6

ATOM 2118 CDl TRP B 58 23 .036 32 .088 16 .087 1 .00 39 .23 6

ATOM 2119 NEl TRP B 58 24 .354 32 .404 15 .917 1 .00 36 .19 7

ATOM 2120 CZ2 TRP B 58 26 .336 32 .452 17 .444 1 .00 40 .36 6

ATOM 2121 CZ3 TRP B 58 25 .778 31 .789 19 .701 1 .00 38 .85 6

ATOM 2122 CH2 TRP B 58 26 .708 32 .215 18 .742 1 .00 40 .16 6

ATOM 2123 C TRP B 58 21 .430 29 .217 16 .561 1 .00 43 .00 6

ATOM 2124 O TRP B 58 22 .226 28 .320 16 .383 1 .00 44 .24 8 ATOM 2125 N SER B 59 20..711 29.,729 15..579 1.00 47.,57 7

ATOM 2126 CA SER B 59 20. .814 29. .181 14. .246 1. ,00 50. .36 6

ATOM 2127 CB SER B 59 19. .517 28. .410 13. ,937 1. .00 52, .43 6

ATOM 2128 OG SER B 59 19. .677 27. .455 12. .901 1. .00 58. .14 8

ATOM 2129 C SER B 59 21. .073 30. ,250 13. .191 1. .00 51, .80 6

ATOM 2130 O SER B 59 20. ,440 31. ,307 13. ,184 1. ,00 48. .66 8

ATOM 2131 N ASP B 60 22, .018 29. .954 12. .303 1. ,00 53. ,93 7

ATOM 2132 CA ASP B 60 22, .393 30, .844 11. .206 1. .00 56, .01 6

ATOM 2133 CB ASP B 60 23, .766 31, .462 11, .474 1. .00 57. .13 6

ATOM 2134 CG ASP B 60 24. .163 32, ,503 10. .437 1. .00 58, .21 6

ATOM 2135 ODl ASP B 60 23. .714 32. .413 9. ,275 1. ,00 56, ,08 8

ATOM 2136 OD2 ASP B 60 24. .952 33, ,407 10, .786 1. ,00 59, .82 8

ATOM 2137 C ASP B 60 22, ,453 29. .976 9. ,953 1. ,00 57. ,25 6

ATOM 2138 O ASP B 60 23, ,458 29. ,315 9. .683 1. .00 57. .02 8

ATOM 2139 N ARG B 61 21. .370 29 .979 9, .192 1, ,00 59 .51 7

ATOM 2140 CA ARG B 61 21 .281 29 .171 7 .981 1. .00 62 .14 6

ATOM 2141 CB ARG B 61 19, .852 29, .202 7, .418 1, .00 65 .88 6

ATOM 2142 CG ARG B 61 18, ,842 28, .288 8, .125 1. .00 71, .80 6

ATOM 2143 CD ARG B 61 17. ,562 28, ,189 7. .282 1. .00 79, ,30 6

ATOM 2144 NE ARG B 61 16, .561 27, .245 7, .806 1. .00 85, .93 7

ATOM 2145 CZ ARG B 61 15, ,393 26. .967 7. .210 1. ,00 88, .02 6

ATOM 2146 NHl ARG B 61 15, .059 27, .553 6, .059 1. .00 89, .55 7

ATOM 2147 NH2 ARG B 61 14, .550 26 .101 7, .762 1. .00 88. .72 7

ATOM 2148 C ARG B 61 22, .256 29, .537 6, .868 1. .00 61, .20 6

ATOM 2149 O ARG B 61 22, .488 28, .725 5 .972 1. .00 61 .95 8

ATOM 2150 N THR B 62 22, .819 30, .742 6, .898 1. .00 59, .72 7

ATOM 2151 CA THR B 62 23. .755 31, .133 5, ,846 1. .00 59. .39 6

ATOM 2152 CB THR B 62 24. ,072 32. ,653 5. .878 1. ,00 61. ,53 6

ATOM 2153 OG1 THR B 62 24 .790 32, .981 7, .077 1. .00 62, .67 8

ATOM 2154 CG2 THR B 62 22 .783 33 .461 5, .826 1, .00 61 .46 6

ATOM 2155 C THR B 62 25, .055 30 .355 5, .992 1. .00 58 .40 6

ATOM 2156 O THR B 62 25, .923 30, .410 5, .129 1. ,00 58, .95 8

ATOM 2157 N LEU B 63 25 .176 29, .626 7 .095 1, ,00 57, .74 7

ATOM 2158 CA LEU B 63 26, .365 28, .831 7, .381 1. ,00 55, .00 6

ATOM 2159 CB LEU B 63 26. .677 28, .871 8, .880 1. ,00 53, .55 6

ATOM 2160 CG LEU B 63 26, .908 30, .230 9 .531 1. .00 52, .72 6

ATOM 2161 CDl LEU B 63 27, .061 30 .070 11 .038 1, ,00 53 .77 6

ATOM 2162 CD2 LEU B 63 28 .141 30 .866 8 .929 1, .00 52 .77 6

ATOM 2163 C LEU B 63 26 .163 27 .377 6 .971 1, .00 54 .84 6

ATOM 2164 O LEU B 63 27 .125 26, .624 6 .858 1. .00 55 .28 8

ATOM 2165 N ALA B 64 24, .911 26, .986 6, .767 1. ,00 53, .09 7

ATOM 2166 CA ALA B 64 24 .579 25, .621 6 .403 1, .00 54 .25 6

ATOM 2167 CB ALA B 64 23 .078 25 .474 6 .274 1 .00 54 .84 6

ATOM 2168 C ALA B 64 25 .235 25 .173 5 .116 1 .00 54 .35 6

ATOM 2169 O ALA B 64 25 .441 25 .973 4 .208 1, .00 56 .81 8

ATOM 2170 N TRP B 65 25 .543 23 .884 5 .040 1, .00 50 .85 7

ATOM 2171 CA TRP B 65 26 .148 23 .305 3 .851 1, .00 50 .36 6

ATOM 2172 CB TRP B 65 27 .674 23 .449 3 .895 1 .00 47 .85 6

ATOM 2173 CG TRP B 65 28, .356 22, .496 4 .836 1. .00 44, .59 6

ATOM 2174 CD2 TRP B 65 28 .626 22 .704 6 .229 1 .00 42 .42 6

ATOM 2175 CE2 TRP B 65 29 .244 21 .535 6 .711 1 .00 41 .31 6

ATOM 2176 CE3 TRP B 65 28 .406 23 .766 7 .115 1 .00 39 .86 6

ATOM 2177 CDl TRP B 65 28 .809 21 .247 4 .544 1, .00 43 .65 6

ATOM 2178 NEl TRP B 65 29 .344 20 .664 5. .662 1, .00 42, .95 7

ATOM 2179 CZ2 TRP B 65 29 .645 21 .393 8 .041 1 .00 41 .27 6

ATOM 2180 CZ3 TRP B 65 28 .807 23 .624 8 .439 1, .00 39 .24 6

ATOM 2181 CH2 TRP B 65 29 .419 22 .445 8 .886 1 .00 40 .26 6

ATOM 2182 C TRP B 65 25 .751 21 .835 3 .839 1 .00 51 .92 6

ATOM 2183 O TRP B 65 25 .269 21 .312 4 .846 1 .00 51 .65 8

ATOM 2184 N ASN B 66 25 .933 21 .173 2 .703 1 .00 54 .28 7

ATOM 2185 CA ASN B 66 25 .579 19 .760 2 .599 1 .00 56 .88 6 ATOM 2186 CB ASN B 66 25.361 19.,349 1.,139 1.,00 59.16 6

ATOM 2187 CG ASN B 66 25. 067 17. .869 1. ,006 1. 00 62. 92 6

ATOM 2188 ODl ASN B 66 25. 084 17. ,308 -0. ,090 1. 00 64. 20 8

ATOM 2189 ND2 ASN B 66 24. 792 17. 223 2. 138 1. 00 63. 82 7

ATOM 2190 C ASN B 66 26. 684 18. ,903 3. ,197 1. ,00 56. 22 6

ATOM 2191 O ASN B 66 27. 826 18. ,942 2. ,747 1. ,00 54. ,74 8

ATOM 2192 N SER B 67 26. 336 18. ,112 4. ,200 1. .00 57. 45 7

ATOM 2193 CA SER B 67 27. ,323 17. ,276 4. ,866 1. .00 60. ,21 6

ATOM 2194 CB SER B 67 27. 251 17. ,503 6. 376 1. 00 60. 70 6

ATOM 2195 OG SER B 67 25. 956 17. ,197 6. ,844 1. ,00 59. ,26 8

ATOM 2196 C SER B 67 27. .139 15. ,796 4. ,554 1. ,00 60. ,90 6

ATOM 2197 O SER B 67 27. .705 14. .926 5. .221 1. ,00 59. .74 8

ATOM 2198 N SER B 68 26. .350 15. .519 3. .528 1. ,00 62, .89 7

ATOM 2199 CA SER B 68 26. .094 14. .148 3. .129 1. ,00 64. .44 6

ATOM 2200 CB SER B 68 25. ,141 14, ,127 1. ,933 1. ,00 64. 07 6

ATOM 2201 OG SER B 68 25. .569 15, ,023 0. ,923 1. ,00 65. ,05 8

ATOM 2202 C SER B 68 27. ,399 13, ,437 2. ,790 1. ,00 65. .22 6

ATOM 2203 O SER B 68 27. ,491 12, ,215 2. ,898 1. ,00 65. ,18 8

ATOM 2204 N HIS B 69 28. .414 14, .203 2. .401 1. ,00 66. ,21 7

ATOM 2205 CA HIS B 69 29. .702 13, .617 2. .054 1, .00 66, .70 6

ATOM 2206 CB HIS B 69 29. .832 13. ,502 0, .539 1, .00 69. .64 6

ATOM 2207 CG HIS B 69 29. .047 12. ,363 -0. .025 1. ,00 74. .89 6

ATOM 2208 CD2 HIS B 69 29. .433 11, .123 -0, .417 1. .00 76. .05 6

ATOM 2209 NDl HIS B 69 27, .673 12, .393 -0, .143 1, .00 76, .35 7

ATOM 2210 CEl HIS B 69 27, .245 11, .221 -0, .583 1, .00 76, .49 6

ATOM 2211 NE2 HIS B 69 28, .293 10, .433 -0, .757 1, .00 76, ,65 7

ATOM 2212 C HIS B 69 30. .895 14. .352 2, .633 1, ,00 65. .56 6

ATOM 2213 O HIS B 69 31. .919 14. .538 1. .971 1. ,00 63. .93 8

ATOM 2214 N SER B 70 30. .746 14, .737 3, .897 1, .00 65, .07 7

ATOM 2215 CA SER B 70 31 .772 15 .463 4 .632 1, .00 63, .00 6

ATOM 2216 CB SER B 70 31 .954 16 .854 4 .004 1 .00 61 .97 6

ATOM 2217 OG SER B 70 30. .716 17 .393 3, .551 1, .00 59, .22 8

ATOM 2218 C SER B 70 31, .353 15, .576 6. .105 1. .00 62, .92 6

ATOM 2219 O SER B 70 30, .288 15, .077 6, .507 1, .00 62, .73 8

ATOM 2220 N PRO B 71 32, .204 16. .199 6. ,937 1. .00 62. .42 7

ATOM 2221 CD PRO B 71 33 .624 16 .490 6 .672 1. .00 61 .13 6

ATOM 2222 CA PRO B 71 31 .901 16 .371 8 .361 1 .00 61 .29 6

ATOM 2223 CB PRO B 71 33 .124 17 .103 8 .879 1 .00 ,61 .30 6

ATOM 2224 CG PRO B 71 34, .214 16, .490 8. .063 1. .00 60. .40 6

ATOM 2225 C PRO B 71 30 .619 17 .159 8, .575 1. .00 61, .12 6

ATOM 2226 O PRO B 71 30 .222 17 .964 7, .733 1 .00 60 .52 8

ATOM 2227 N ASP B 72 29 .973 16, .916 9, .708 1, .00 62, .69 7

ATOM 2228 CA ASP B 72 28 .714 17 .587 10 .046 1 .00 62 .55 6

ATOM 2229 CB ASP B 72 27 .839 16 .649 10 .883 1 .00 64 .34 6

ATOM 2230 CG ASP B 72 27 .143 15 .613 10, .040 1. .00 67, .53 6

ATOM 2231 ODl ASP B 72 25 .937 15 .794 9 .767 1 .00 67 .60 8

ATOM 2232 OD2 ASP B 72 27 .808 14 .627 9 .631 1 .00 70 .97 8

ATOM 2233 C ASP B 72 28 .962 18 .858 10 .827 1 .00 60 .43 6

ATOM 2234 O ASP B 72 28 .137 19 .780 10 .815 1 .00 58 .20 8

ATOM 2235 N GLN B 73 30 .123 18 .883 11 .483 1 .00 58 .87 7

ATOM 2236 CA GLN B 73 30 .549 19 .981 12, .339 1 .00 58 .03 6

ATOM 2237 CB GLN B 73 30 .400 19 .583 13 .788 1 .00 60 .56 6

ATOM 2238 CG GLN B 73 ^•29 .025 19 .532 14 .346 1 .00 62 .56 6

ATOM 2239 CD GLN B 73 29 .096 19 .033 15 .763 1 .00 64 .10 6

ATOM 2240 OEl GLN B 73 29 .599 17 .945 16 .003 1 .00 67 .42 8

ATOM 2241 NE2 GLN B 73 28 .628 19 .830 16 .711 1 .00 65 .84 7

ATOM 2242 C GLN B 73 31 .998 20 .392 12 .165 1 .00 55 .43 6

ATOM 2243 0 GLN B 73 32 .845 19 .591 11 .754 1 .00 56 .41 8

ATOM 2244 N VAL B 74 32 .275 21 .642 12 .522 1 .00 50 .91 7

ATOM 2245 CA VAL B 74 33 .621 22 .197 12 .464 1 .00 48 .23 6

ATOM 2246 CB VAL B 74 33 .925 22 .849 11 .107 1 .00 46 .99 6 ATOM 2247 CGI VAL B 74 34.009 21.782 10.026 1.00 48.63 6

ATOM 2248 CG2 VAL B 74 32. 864 23. 871 10. 777 1. 00 45. 41 6

ATOM 2249 C VAL B 74 33. 734 23. 259 13. 532 1. 00 46. 89 6

ATOM 2250 O VAL B 74 32. 731 23. 812 13. 964 1. 00 46. 87 8

ATOM 2251 N SER B 75 34. 951 23. ,524 13. 980 1. 00 44. 18 7

ATOM 2252 CA SER B 75 35. 177 24. .551 14. .982 1. ,00 41. ,30 6

ATOM 2253 CB SER B 75 36. 314 24. 145 15. 920 1. 00 39. 05 6

ATOM 2254 OG SER B 75 35. 850 23. .290 16. ,932 1. 00 30. ,94 8

^• ATOM 2255 C SER B 75 35. 513 25. .856 14. 264 1. 00 40. ,02 6

ATOM 2256 O SER B 75 36. ,478 25. .936 13. ,516 1. ,00 39, ,74 8

ATOM 2257 N VAL B 76 34. 701 26. .875 14. ,497 1. 00 39. ,53 7

ATOM 2258 CA VAL B 76 34. 885 28. ,167 13. 861 1. 00 40. 26 6

ATOM 2259 CB VAL B 76 33. 607 28. .580 13. ,124 1. 00 42. ,73 6

ATOM 2260 CGI VAL B 76 33. 788 29. .928 12. 483 1. 00 43. ,36 6

ATOM 2261 CG2 VAL B 76 33. .244 27, .539 12, .090 1. ,00 40. ,50 6

ATOM 2262 C VAL B 76 35. ,218 29. ,256 14. .861 1. 00 40. ,57 6

ATOM 2263 O VAL B 76 34. .626 29. .322 15. .926 1. ,00 41, .80 8

ATOM 2264 N PRO B 77 36. .188 30. .120 14, .541 1. .00 40, .43 7

ATOM 2265 CD PRO B 77 37. .176 30. ,053 13, ,460 1. ,00 39. ,25 6

ATOM 2266 CA PRO B 77 36. .527 31. .189 15, .479 1. ,00 39. .73 6

ATOM 2267 CB PRO B 77 37. 717 31. .853 14. ,816 1. 00 40. ,77 6

ATOM 2268 CG PRO B 77 38. .342 30, .728 14. .078 1. ,00 40, .80 6

ATOM 2269 C PRO B 77 35. ,346 32. .141 15. .622 1. ,00 38. ,02 6

ATOM 2270 O PRO B 77 34. .663 32, .438 14, .658 1. ,00 39, ,36 8

ATOM 2271 N ILE B 78 35, .105 32 .600 16 .835 1. .00 37 .63 7

ATOM 2272 CA ILE B 78 34. .018 33, .515 17. .129 1, .00 39, ,61 6

ATOM 2273 CB ILE B 78 34. .107 33 .946 18, .602 1. ,00 41, .86 6

ATOM 2274 CG2 ILE B 78 33. .311 35. .183 18, .861 1. .00 40, .86 6

ATOM 2275 CGI ILE B 78 33, .622 32 .799 19 .469 1. .00 45 .04 6

ATOM 2276 CDl ILE B 78 32. .313 32. .232 18, .983 1, ,00 46, ,64 6

ATOM 2277 C ILE B 78 34. .000 34 .741 16, .231 1. .00 41, .00 6

ATOM 2278 O ILE B 78 32, .947 35 .225 15 .846 1. .00 41 .00 8

ATOM 2279 N SER B 79 35. .185 35. .227 15, .898 1. .00 43. .87 7

ATOM 2280 CA SER B 79 35, .368 36 .399 15 .047 1, .00 44 .52 6

ATOM 2281 CB SER B 79 36. .842 36, .792 15. .061 1, ,00 46. ,91 6

ATOM 2282 OG SER B 79 37 .657 35 .687 14 .696 1, .00 49 .85 8

ATOM 2283 C SER B 79 34, .914 36 .244 13 .593 1, .00 43 .47 6

ATOM 2284 O SER B 79 3 .805 37 .228 12 .876 1 .00 43 .49 8

ATOM 2285 N SER B 80 34 .656 35 .016 13 .160 1, .00 43 .24 7

ATOM 2286 CA SER B 80 34, .227 34 .769 11 .793 1. ,00 44, .14 6

ATOM 2287 CB SER B 80 3 .955 33 .552 11 .221 1, .00 44 .85 6

ATOM 2288 OG SER B 80 36 .354 33 .781 11 .115 1, .00 52 .06 8

ATOM 2289 C SER B 80 32 .731 34 .545 11 .690 1 .00 44 .49 6

ATOM 2290 O SER B 80 32, .213 34 .308 10 .609 1, .00 44, .54 8

ATOM 2291 N LEU B 81 32 .039 34 .625 12 .820 1 .00 45 .89 7

ATOM 2292 CA LEU B 81 30 .589 34 .418 12 .858 1 .00 45 .78 6

ATOM 2293 CB LEU B 81 30 .250 33 .187 13 .700 1 .00 42 .48 6

ATOM 2294 CG LEU B 81 30 .945 31 .867 13 .420 1 .00 42 .60 6

ATOM 2295 CDl LEU B 81 30 .769 30 .949 14 .584 1 .00 41 .27 6

ATOM 2296 CD2 LEU B 81 30 .379 31 .266 12 .165 1 .00 45 .70 6

ATOM 2297 C LEU B 81 29 .909 35 .611 13 .513 1 .00 45 .11 6

ATOM 2298 O LEU B 81 30 .562 36 .439 .14 .154 1 .00 46 .02 8

ATOM 2299 N TRP B 82 28 .596 35 .696 13 .344 1 .00 42 .92 7

ATOM 2300 CA TRP B 82 27 .829 36 .737 13 .984 1 .00 40 .24 6

ATOM 2301 CB TRP B 82 26 .493 36 .962 13 .290 1 .00 42 .22 6

ATOM 2302 CG TRP B 82 25 .535 37 .766 14 .126 1 .00 43 .85 6

ATOM 2303 CD2 TRP B 82 24 .580 37 .257 15 .072 1 .00 44 .14 6

ATOM 2304 CE2 TRP B 82 23 .972 38 .369 15 .687 1 .00 42 .05 6

ATOM 2305 CE3 TRP B 82 24 .185 35 .964 15 .461 1 .00 42 .43 6

ATOM 2306 CDl TRP B 82 25 .459 39 .118 14 .204 1 .00 42 .92 6

ATOM 2307 NEl TRP B 82 24 .527 39 .490 15 .138 1 .00 41 .43 7 ATOM 2308 CZ2 TRP B 82 22.991 38.238 16.,671 1.00 42.94 6

ATOM 2309 CZ3 TRP B 82 23. ,211 35. ,832 16. .442 1. 00 41. 79 6

ATOM 2310 CH2 TRP B 82 22. .625 36. .965 17 .036 1. .00 42. .57 6

ATOM 2311 C TRP B 82 27. .579 36. ,100 15. .323 1. .00 39. ,43 6

ATOM 2312 O TRP B 82 27. ,379 34. 904 15. .410 1. 00 41. 05 8

ATOM 2313 N VAL B 83 27. .594 36. ,892 16. .373 1. 00 41. ,18 7

ATOM 2314 CA VAL B 83 27. ,363 36. ,359 17. ,699 1. 00 40. ,57 6

ATOM 2315 CB VAL B 83 28. .714 36. .210 18, ,444 1. ,00 41. ,00 6

ATOM 2316 CGI VAL B 83 28, .494 35. ,956 19. .903 1. 00 45. ,57 6

ATOM 2317 CG2 VAL B 83 29, ,491 35. .066 17 .856 1. ,00 40. .97 6

ATOM 2318 C VAL B 83 26. ,399 37. ,275 18, ,460 1. 00 40. ,40 6

ATOM 2319 O VAL B 83 26. .424 38. ,487 18, .301 1. 00 42. ,78 8

ATOM 2320 N PRO B 84 25, .510 36. ,693 19, .271 1. ,00 40. ,62 7

ATOM 2321 CD PRO B 84 25. .296 35. ,250 19, .465 1. ,00 43. ,06 6

ATOM 2322 CA PRO B 84 24. .540 37. .460 20. .052 1. ,00 39. .62 6

ATOM 2323 CB PRO B 84 23, .839 36, .384 20, .880 1. .00 39. .00 6

ATOM 2324 CG PRO B 84 23, .899 35, .212 20 .013 1. .00 43. .18 6

ATOM 2325 C PRO B 84 25, .246 38, .474 20, .937 1. .00 37. ,37 6

ATOM 2326 O PRO B 84 26. .215 38. ,140 21. .603 1. 00 34. ,20 8

ATOM 2327 N ASP B 85 24, .753 39. .706 20, .950 1. .00 36. ,29 7

ATOM 2328 CA ASP B 85 25, .341 40. ,736 21, .777 1. .00 37. ,57 6

ATOM 2329 CB ASP B 85 25, .112 42. .107 21, .152 1. ,00 38, ,52 6

ATOM 2330 CG ASP B 85 23, .661 42, .418 20. .952 1. ,00 40. ,81 6

ATOM 2331 ODl ASP B 85 22, .925 41. .501 20, .578 1. ,00 41. .81 8

ATOM 2332 OD2 ASP B 85 23 .254 43, ,579 21, .148 1. .00 41, .12 8

ATOM 2333 C ASP B 85 24, .776 40. .687 23, .193 1. ,00 39. .08 6

ATOM 2334 O ASP B 85 24. .261 41, .668 23. .714 1. ,00 36. .01 8

ATOM 2335 N LEU B 86 24, .902 39, ,522 23, .811 1. ,00 38. ,19 7

ATOM 2336 CA LEU B 86 24 .421 39, ,306 25 .161 1. ,00 39. .63 6

ATOM 2337 CB LEU B 86 24, .459 37. .819 25, .502 1. ,00 37. ,18 6

ATOM 2338 CG LEU B 86 23, .585 36, .939 24, .621 1. .00 38, .33 6

ATOM 2339 CDl LEU B 86 23, .700 35. ,493 25, .065 1. ,00 33. ,72 6

ATOM 2340 CD2 LEU B 86 22, .159 37. .433 24, .693 1. .00 35. .49 6

ATOM 2341 C LEU B 86 25, .223 40. .061 26. .201 1. .00 40. .05 6

ATOM 2342 O LEU B 86 26. .432 40. .251 26. .065 1. ,00 42. ,26 8

ATOM 2343 N ALA B 87 24, .541 40. ,467 27. .260 1. ,00 40. .28 7

ATOM 2344 CA ALA B 87 25 .180 41, ,193 28, .339 1. .00 40. .51 6

ATOM 2345 CB ALA B 87 25 .048 42, .698 28 .091 1. .00 40, .62 6

ATOM 2346 C ALA B 87 24 .521 40, .826 29, .660 1. ,00 40, .28 6

ATOM 2347 O ALA B 87 23, .306 40, .702 29, .729 1. ,00 40, ,56 8

ATOM 2348 N ALA B 88 25 .316 40 .634 30 .703 1. .00 39 .13 7

ATOM 2349 CA ALA B 88 24, .756 40, ,340 32, .014 1. ,00 38, ,99 6

ATOM 2350 CB ALA B 88 25 .749 39, .577 32 .850 1. .00 37, .09 6

ATOM 2351 C ALA B 88 24 .433 41 .686 32 .665 1, .00 40 .68 6

ATOM 2352 O ALA B 88 25 .319 42 .392 33 .134 1 .00 38 .34 8

ATOM 2353 N TYR B 89 23 .153 42 .033 32 .667 1. .00 42 .45 7

ATOM 2354 CA TYR B 89 22 .654 43. .285 33 .232 1, .00 44, .08 6

ATOM 2355 CB TYR B 89 21 .133 43 .209 33 .363 1 .00 46 .62 6

ATOM 2356 CG TYR B 89 20 .395 43 .055 32 .056 1, . 00 51 .23 6

ATOM 2357 CDl TYR B 89 19 .022 42 .816 32 .036 1 .00 54 .25 6

ATOM 2358 CEl TYR B 89 18 .322 42 .711 30 .826 1 .00 55 .90 6

ATOM 2359 CD2 TYR B 89 21 .054 43 .179 30 .835 1 .00 52 .13 6

ATOM 2360 CE2 TYR B 89 20 .366 43 .078 29 .626 1 .00 54 .28 6

ATOM 2361 CZ TYR B 89 19 .001 42 .847 29 .629 1. .00 55 .97 6

ATOM 2362 OH TYR B 89 18 .313 42 .787 28 .440 1 .00 59 .26 8

ATOM 2363 C TYR B 89 23 .243 43 .725 34 .579 1 .00 43 .48 6

ATOM 2364 O TYR B 89 23 .409 44 .917 34 .820 1 .00 42 .18 8

ATOM 2365 N ASN B 90 23 .540 42 .784 35 .466 1 .00 42 .08 7

ATOM 2366 CA ASN B 90 24 .102 43 .155 36 .755 1 .00 40 .43 6

ATOM 2367 CB ASN B 90 23 .262 42 .581 37 .904 1 .00 39 .29 6

ATOM 2368 CG ASN B 90 23 .084 41 .082 37 .824 1 .00 40 .77 6 ATOM 2369 ODl ASN B 90 22.778 40.536 36.774 1.00 40.90 8

ATOM 2370 ND2 ASN B 90 23. 257 40. 412 38. 948 1. 00 42. 41 7

ATOM 2371 C ASN B 90 25. 554 42. 768 36. 921 1. 00 41. 50 6

ATOM 2372 O ASN B 90 26. 031 42. 618 38. 042 1. 00 42. 85 8

ATOM 2373 N ALA B 91 26. 250 42. 605 35. 798 1. 00 43. 60 7

ATOM 2374 CA ALA B 91 27. 669 42. 266 35. 811 1. 00 43. 31 6

ATOM 2375 CB ALA B 91 28. 156 41. 933 34. 415 1. 00 42. 36 6

ATOM 2376 C ALA B 91 28. 359 43. 513 36. 336 1. 00 44. ,47 6

ATOM 2377 O ALA B 91 28. ,048 44. ,637 35. ,934 1. 00 43. .75 8

ATOM 2378 N ILE B 92 29. 295 43. 299 37. 244 1. 00 44. 99 7

ATOM 2379 CA ILE B 92 30. ,009 44. ,379 37. ,895 1. 00 45. . 69 6

ATOM 2380 CB ILE B 92 30. 052 44. 061 39. 418 1. 00 46. ,91 6

ATOM 2381 CG2 ILE B 92 31. ,419 43. ,514 39. .831 1. ,00 49. ,50 6

ATOM 2382 CGI ILE B 92 29. 726 45. 288 40. ,232 1. 00 48. ,64 6

ATOM 2383 CDl ILE B 92 29. .920 45. ,030 41. .718 1. ,00 53. .73 6

ATOM 2384 C ILE B 92 31. 428 44. 532 37. ,302 1. 00 45. ,86 6

ATOM 2385 O ILE B 92 32, .156 45. ,487 37. ,611 1. ,00 45. .24 8

ATOM 2386 N SER B 93 31. ,804 43. ,581 36. ,453 1. 00 41. .25 7

ATOM 2387 CA SER B 93 33. ,104 43. ,578 - 35. ,813 1. 00 38. ,58 6

ATOM 2388 CB SER B 93 34. ,056 42. ,662 36. ,568 1. .00 35. ,19 6

ATOM 2389 OG SER B 93 33. ,682 41. ,315 36, .388 1. .00 35, .43 8

ATOM 2390 C SER B 93 32, .852 43, .015 34, .431 1. ,00 40, .88 6

ATOM 2391 O SER B 93 31, .776 42, ,493 34, .174 1. .00 39, .63 8

ATOM 2392 N LYS B 94 33 .815 43, .131 33, ,524 1. .00 43, .16 7

ATOM 2393 CA LYS B 94 33. ,598 42. ,557 32, .212 1. .00 43, .98 6

ATOM 2394 CB LYS B 94 34, .355 43, .325 31 .127 1. ,00 46 .29 6

ATOM 2395 CG LYS B 94 35, .769 43, .727 31, .434 1. .00 50 .31 6

ATOM 2396 CD LYS B 94 36, .225 44, .764 30, .401 1. .00 52, .39 6

ATOM 2397 CE LYS B 94 35, .853 44, .341 28, .978 1, ,00 52, .02 6

ATOM 2398 NZ LYS B 94 36, .333 45, .308 27, .965 1. ,00 54, .82 7

ATOM 2399 C LYS B 94 33, .963 41, .075 32, .230 1, ,00 43, .71 6

ATOM 2400 O LYS B 94 34. .673 40, .602 33 .114 1, .00 4 .78 8

ATOM 2401 N PRO B 95 33, .443 40. ,310 31. ,267 1. ,00 44, ,16 7

ATOM 2402 CD PRO B 95 32. .562 40, .750 30, .171 1, .00 42, .37 6

ATOM 2403 CA PRO B 95 33. .704 38, .873 31, .184 1, .00 39, .82 6

ATOM 2404 CB PRO B 95 32 .836 38 .422 30 .016 1. .00 40 .83 6

ATOM 2405 CG PRO B 95 31 .813 3θ .505 29 .881 1 .00 42 .58 6

ATOM 2406 C PRO B 95 35 .141 38 .524 30 .941 1 .00 39 .41 6

ATOM 2407 O PRO B 95 35 .772 39 .048 30 .032 1 .00 40 .47 8

ATOM 2408 N GLU B 96 35 .663 37 .637 31 .765 1 .00 39 .61 7

ATOM 2409 CA GLU B 96 37 .020 37 .175 31 .582 1 .00 39 .82 6

ATOM 2410 CB GLU B 96 37 .765 37 .046 32 .915 1 .00 41 .36 6

ATOM 2411 CG GLU B 96 39 .238 36 .644 32 .763 1 .00 50 .17 6

ATOM 2412 CD GLU- B 96 39 .989 36 .540 34 .094 1 .00 55 .05 6

ATOM 2413 OEl GLU B 96 39 .506 37 .129 35 .084 1 .00 57 .32 8

ATOM 2414 OE2 GLU B 96 41 .067 35 .888 34 .153 1 .00 56 .17 8

ATOM 2415 C GLU B 96 36 .802 35 .804 30 .966 1 .00 39 .55 6

ATOM 2416 O GLU B 96 36 .537 34 .840 31 .676 1 .00 38 .71 8

ATOM 2417 N VAL B 97 36 .864 35 .736 29 .638 1 .00 36 .87 7

ATOM 2418 CA VAL B 97 36 .690 34 .475 28 .938 1 .00 35 .52 6

ATOM 2419 CB VAL B 97 36 .457 34 .702 27 .448 1 .00 35 .28 6

ATOM 2420 CGI VAL B 97 36 .249 33 .378 26 .752 1 .00 33 .50 6

ATOM 2421 CG2 VAL B 97 35 .249 35 .586 27 .255 1 .00 31 .71 6

ATOM 2422 C VAL B 97 37 .935 33 .640 29 .157 1 .00 35 .07 6

ATOM 2423 O VAL B 97 39 .025 34 .005 28 .741 1 .00 37 .13 8

ATOM 2424 N LEU B 98 37 .759 32 .511 29 .823 1 .00 35 .85 7

ATOM 2425 CA LEU B 98 38 .866 31 .631 30 .167 1 .00 36 .60 6

ATOM 2426 CB LEU B 98 38 .554 30 .913 31 .482 1 .00 37 .34 6

ATOM 2427 CG LEU B 98 38 .127 31 .727 32 .701 1 .00 39 .09 6

ATOM 2428 CDl LEU B 98 37 .534 30 .812 33 .739 1 .00 37 .97 6

ATOM 2429 CD2 LEU B 98 39 .306 32 .469 33 .259 1 .00 41 .28 6 ATOM 2430 C LEU B 98 39..198 30.,581 29..128 1.,00 36.,56 6

ATOM 2431 O LEU B 98 40. ,195 29. ,889 29. ,251 1. ,00 37. ,06 8

ATOM 2432 N THR B 99 38. ,371 30. .467 28, .103 1. .00 36. ,66 7

ATOM 2433 CA THR B 99 38. ,578 29. ,438 27. .100 1. .00 37. ,03 6

ATOM 2434 CB THR B 99 37. ,405 28, ,414 27. .142 1. .00 40. ,73 6

ATOM 2435 OG1 THR B 99 36. ,152 29, .097 26. .972 1. .00 42. ,70 8

ATOM 2436 CG2 THR B 99 37. .400 27. .676 28. .466 1. ,00 37. .60 6

ATOM 2437 C THR B 99 38. .725 29. .932 25, .680 1, .00 34. .89 6

ATOM 2438 O THR B 99 38. .401 31. .073 25. .378 1. .00 35. .25 8

ATOM 2439 N PRO B 100 39. ,231 29, .066 24, .786 1. .00 35. ,40 7

ATOM 2440 CD PRO B 100 39, .818 27. .745 25. .056 1. .00 33. ,38 6

ATOM 2441 CA PRO B 100 39. .413 29. .420 23. .380 1. ,00 35. ,17 6

ATOM 2442 CB PRO B 100 39. .783 28. .095 22, .745 1. .00 33. .58 6

ATOM 2443 CG PRO B 100 40. ,603 27. ,476 23, ,789 1. .00 34. .20 6

ATOM 2444 C PRO B 100 38. .107 29, ,961 22. ,852 1. .00 37. ,17 6

ATOM 2445 O PRO B 100 37. .052 29. ,396 23. .103 1. .00 38. ,59 8

ATOM 2446 N GLN B 101 38, .168 31. .066 22, .130 1, .00 39, ,08 7

ATOM 2447 CA GLN B 101 36 .949 31, .636 21 .621 1, .00 40, .23 6

ATOM 2448 CB GLN B 101 37. .071 33. .155 21. ,576 1, .00 39, .84 6

ATOM 2449 CG GLN B 101 36 .866 33 .742 22 .960 1, .00 45, .68 6

ATOM 2450 CD GLN B 101 37. .334 35, .158 23, .075 1, .00 47, .02 6

ATOM 2451 OEl GLN B 101 36 .871 36 .035 22 .350 1 .00 50 .05 8

ATOM 2452 NE2 GLN B 101 38, .260 35. .398 23. ,997 1, .00 45. .46 7

ATOM 2453 C GLN B 101 36, .536 31, .057 20, .295 1. .00 39, .08 6

ATOM 2454 O GLN B 101 36 .496 31 .747 19, .282 1, .00 37, .88 8

ATOM 2455 N LEU B 102 36, .212 29, .768 20, .342 1, .00 40, .24 7

ATOM 2456 CA LEU B 102 35, .770 28, .997 19, .183 1, .00 39, .64 6

ATOM 2457 CB LEU B 102 36 .652 27. .759 18. ,982 1. .00 37. .23 6

ATOM 2458 CG LEU B 102 38 .155 27 .988 18 .842 1 .00 37, .24 6

ATOM 2459 CDl LEU B 102 38, .852 26, .666 18, .659 1, .00 33, .59 6

ATOM 2460 CD2 LEU B 102 38. .429 28. .893 17. ,665 1, .00 36, .66 6

ATOM 2461 C LEU B 102 34 .349 28, .528 19, .394 1, .00 39, .73 6

ATOM 2462 O LEU B 102 33 .948 28, .210 20, .502 1, .00 38, .45 8

ATOM 2463 N ALA B 103 33 .586 28 .492 18 .317 1. .00 41, .12 7

ATOM 2464 CA ALA B 103 32, .218 28. .017 18. .375 1. .00 40. .48 6

ATOM 2465 CB ALA B 103 31, .271 29. .034 17. .760 1. .00 39, .15 6

ATOM 2466 C ALA B 103 32 .163 26, .711 17. .599 1, .00 40, .28 6

ATOM 2467 O ALA B 103 33. .109 26. .337 16. ,917 1. .00 38. .52 8

ATOM 2468 N ARG B 104 31 .045 26. .014 17, .715 1. .00 42. .85 7

ATOM 2469 CA ARG B 104 30 .876 24 .755 17, .019 1. .00 44, .21 6

ATOM 2470 CB ARG B 104 30 .557 23 .659 18 .027 1 .00 43 .23 6

ATOM 2471 CG ARG B 104 30 .760 22. .273 17, .496 1. .00 45 .99 6

ATOM 2472 CD ARG B 104 32 .214 21 .957 17 .217 1 .00 44 .48 6

ATOM 2473 NE ARG B 104 32 .306 20 .612 16 .652 1 .00 45 .67 7

ATOM 2474 CZ ARG B 104 33 .434 19 .985 16 .341 1. .00 42 .29 6

ATOM 2475 NHl ARG B 104 34 .593 20 .576 16 .534 1 .00 40 .18 7

ATOM 2476 NH2 ARG B 104 33 .397 18 .755 15 .847 1 .00 43 .70 7

ATOM 2477 C ARG B 104 29 .736 24 .954 16 .040 1 .00 44 .71 6

ATOM 2478 O ARG B 104 28 .655 25 .377 16 .425 1 .00 43 .84 8

ATOM 2479 N VAL B 105 29 .990 24 .686 1 .767 1 .00 45 .98 7

ATOM 2480 CA VAL B 105 28 .955 24 .862 13, .761 1 .00 46 .86 6

ATOM 2481 CB VAL B 105 29 .404 25 .834 12, .663 1, . 00 43, .67 6

ATOM 2482 CGI VAL B 105 28 .257 26 .111 11 .715 1 .00 42 .93 6

ATOM 2483 CG2 VAL B 105 29 .885 27 .116 13, .281 1 .00 41, .79 6

ATOM 2484 C VAL B 105 28 .546 23 .546 13 .112 1 .00 50 .58 6

ATOM 2485 O VAL B 105 29 .393 22 .808 12, .589 1 .00 51, .09 8

ATOM 2486 N VAL B 106 27 .243 23 .266 13 .158 1. .00 51 .24 7

ATOM 2487 CA VAL B 106 26 .677 22 .056 12, .577 1, .00 52 .00 6

ATOM 2488 CB VAL B 106 25 .464 21 .592 13, .387 1, .00 52, .31 6

ATOM 2489 CGI VAL B 106 25 .038 20 .207 12 .931 1. .00 52 .15 6

ATOM 2490 CG2 VAL B 106 25 .798 21 .607 14, .865 1 .00 50 .55 6 ATOM 2491 C VAL B 106 26.243 22.369 11.147 1.00 52.00

ATOM 2492 O VAL B 106 25.782 23.474 10.870 1.00 52.80

ATOM 2493 N SER B 107 26.388 21.401 10.248 1.00 51.28

ATOM 2494 CA SER B 107 26.038 21.592 8.845 1.00 52.41

ATOM 2495 CB SER B 107 26.175 20.272 8.097 1.00 54.05

ATOM 2496 OG SER B 107 25.609 19.216 8.855 1.00 58.60

ATOM 2497 C SER B 107 24.676 22.198 8.544 ,00 52.33

ATOM 2498 O SER B 107 24.469 22.728 7.460 ,00 52.31

ATOM 2499 N ASP B 108 23.753 22.132 9.494 1.00 54.48

ATOM 2500 CA ASP B 108 22.417 22.687 9.285 1.00 57.36

ATOM 2501 CB ASP B 108 21.376 21.830 10.007 1. .00 59, .13

ATOM 2502 CG ASP B 108 21.474 21.933 11.512 1. .00 61. .77

ATOM 2503 ODl ASP B 108 22.604 21.993 12.034 1, .00 63. .26

ATOM 2504 OD2 ASP B 108 20.419 21.941 12.180 1, .00 63, ,13

ATOM 2505 C ASP B 108 22.266 24.152 9.715 1, .00 58, .76

ATOM 2506 O ASP B 108 21.163 24.696 9.711 1, .00 60. ,28

ATOM 2507 N GLY B 109 23.376 24.784 10.087 1, .00 59. .97

ATOM 2508 CA GLY B 109 23.346 26.175 10.489 1, .00 58, .62

ATOM 2509 C GLY B 109 23.213 26.394 11.983 1, .00 59, .08

ATOM 2510 O GLY B 109 23.123 27.534 12.437 1 .00 58, .71

ATOM 2511 N GLU B 110 23.187 25.317 12.758 1 .00 58 .29

ATOM 2512 CA GLU B 110 23.062 25.451 14.202 1 .00 57, .49

ATOM 2513 CB GLU B 110 22.619 24.125 14.827 1 .00 60 . .94

ATOM 2514 CG GLU B 110 21.947 24.234 16.208 1 .00 64 .96

ATOM 2515 CD GLU B 110 20.623 25.007 16.159 1 .00 69 .09

ATOM 2516 OEl GLU B 110 20.054 25.121 15.044 1 .00 70, .48

ATOM 2517 OΞ2 GLU B 110 20.146 25.493 17.223 1 .00 67 .90

ATOM 2518 C GLU B 110 24.432 25.838 14.723 1 .00 56 .48

ATOM 2519 O GLU B 110 25.447 25.291 14.282 1 .00 58 .51

ATOM 2520 N VAL B 111 24.461 26.780 15.656 1 .00 52 .94 7

ATOM 2521 CA VAL B 111 25.706 27.254 16.237 1 .00 .49, .98 6

ATOM 2522 CB VAL B 111 25.933 28.743 15.914 1 .00 50 .06 6

ATOM 2523 CGI VAL B 111 27.259 29.199 16.502 1 .00 48 .91 6

ATOM 2524 CG2 VAL B 111 25.894 28.973 14.406 1 .00 49 .75 6

ATOM 2525 C VAL B 111 25.702 27.095 17.749 1 1. .00 49 .14 6

ATOM 2526 O VAL B 111 24.730 27.431 18.413 11 .,00 47 .85 8

ATOM 2527 N LEU B 112 26.795 26.581 18.292 1. 00 49.78 7

ATOM 2528 CA LEU B 112 26.907 26.404 19.733 1.00 50.84 6

ATOM 2529 CB LEU B 112 26.903 24.914 20.107 1.00 54.21 6

ATOM 2530 CG LEU B 112 26.075 23.868 19.337 00 56.22 6

ATOM 2531 CDl LEU B 112 24.673 24.393 19.025 00 58.51 6

ATOM 2532 CD2 LEU B 112 26.802 23.504 18.065 00 54.95 6

ATOM 2533 C LEU B 112 28.202 27.038 20.242 00 50.58 6

ATOM 2534 O LEU B 112 29.300 26.651 19.829 1.00 51.33 8

ATOM 2535 N TYR B 113 28.073 28.013 21.134 1.00 47.63 7

ATOM 2536 CA TYR B 113 29.227 28.681 21.709 1. 00 46.01 6

ATOM 2537 CB TYR B 113 29.266 30.154 21.279 1. 00 45.50 6

ATOM 2538 CG TYR B 113 30.415 30.970 21.868 1. 00 45.48 6

ATOM 2539 CDl TYR B 113 31.715 30.468 21.902 1. 00 43.49

ATOM 2540 CEl TYR B 113 32.766 31.225 22.412 1.00 42.81

ATOM 2541 CD2 TYR B 113 30.200 32.262 22.367 1, 00 44.88

ATOM 2542 CE2 TYR B 113 31.246 33.022 22.876 1 00 42.75

ATOM 2543 CZ TYR B 113 -32.528 32.499 22.897 1.00 45.11

ATOM 2544 OH TYR B 113 33.579 33.248 23.397 1. .00 46, .12 8

ATOM 2545 C TYR B 113 29.081 28.561 23.208 1. .00 45, .62 6

ATOM 2546 O TYR B 113 28.130 29.064 23.783 1. .00 48, .17 8

ATOM 2547 N MET B 114 30.025 27.887 23.842 1. .00 45 .82 7

ATOM 2548 CA MET B 114 29.966 27.691 25.280 1. .00 47, .40 6

ATOM 2549 CB MET B 114 29.652 26.237 25.578 1, .00 51 .46 6

ATOM 2550 CG MET B 114 29.408 25.958 27.030 1. .00 56, .47 6

ATOM 2551 SD MET B 114 29.463 24.204 27.290 1. ,00 61, .08 16 ATOM 2552 CE MET B 114 27.,833 23.,732 26.,736 1.00 59.,81 6

ATOM 2553 C MET B 114 31. 281 28. ,060 25. ,944 1. 00 47. 40 6

ATOM 2554 O MET B 114 32. .093 27. ,187 26. ,268 1. ,00 46. ,46 8

ATOM 2555 N PRO B 115 31. ,511 29. .364 26. .158 1. .00 46. .76 7

ATOM 2556 CD PRO B 115 30. 680 30. ,502 25. ,712 1. 00 45. 52 6

ATOM 2557 CA PRO B 115 32. ,744 29, ,832 26. ,786 1. ,00 44. ,75 6

ATOM 2558 CB PRO B 115 32. .834 31. ,259 26. ,285 1. .00 47. .19 6

ATOM 2559 CG PRO B 115 31. .382 31, .687 26, .316 1. .00 45. ,23 6

ATOM 2560 C PRO B 115 32. 653 29. ,776 28. ,303 1. ,00 45. ,76 6

ATOM 2561 O PRO B 115 31. 567 29. ,933 28. ,865 1. 00 46. ,79 8

ATOM 2562 N SER B 116 33. .783 29, .545 28. .965 1. .00 44. ,58 7

ATOM 2563 CA SER B 116 33. .797 29, ,527 30, .416 1. .00 42. .97 6

ATOM 2564 CB SER B 116 34. ,867 28. ,605 30. ,935 1. ,00 42, .63 6

ATOM 2565 OG SER B 116 34. ,810 28. ,586 32. ,342 1. ,00 46. ,80 8

ATOM 2566 C SER B 116 34. .124 30. .939 30, .832 1, .00 43, .61 6

ATOM 2567 O SER B 116 35. .144 31. .473 30. ,431 1. .00 45, .91 8

ATOM 2568 N ILE B 117 33. .270 31, .547 31, .643 1, .00 42, ,76 7

ATOM 2569 CA ILE B 117 33. ,483 32, .923 32, .052 1, ,00 40. .88 6

ATOM 2570 CB ILE B 117 32. ,340 33, .816 31, ,515 1, .00 39. ,30 6

ATOM 2571 CG2 ILE B 117 32 .512 35 .249 31 .995 1, .00 40, .17 6

ATOM 2572 CGI ILE B 117 32, .317 33 .760 29, .992 1, .00 37, .44 6

ATOM 2573 CDl ILE B 117 31, ,069 34, .332 29, .394 1. ,00 36, ,96 6

ATOM 2574 C ILE B 117 33, ,592 33. .158 33. ,545 1. ,00 42. .01 6

ATOM 2575 O ILE B 117 32, .840 32 .585 34, .329 1. .00 44, .14 8

ATOM 2576 N ARG B 118 34, .554 33 .986 33 .939 1, .00 42, .44 7

ATOM 2577 CA ARG B 118 34. .683 34. .363 35. .339 1. .00 42. .12 6

ATOM 2578 CB ARG B 118 36, .120 34 .283 35, .835 1. ,00 39, .55 6

ATOM 2579 CG ARG B 118 36, .241 34 .873 37, .226 1, .00 40, .13 6

ATOM 2580 CD ARG B 118 37 .520 34 .517 37 .933 1 .00 40 .72 6

ATOM 2581 NE ARG B 118 37, ,546 35, .120 39, .259 1. .00 43, .73 7

ATOM 2582 CZ ARG B 118 38. ,424 34. .821 40. .204 1. .00 43. .99 6

ATOM 2583 NHl ARG B 118 39 .356 33 .915 39 .973 1. .00 45 .99 7

ATOM 2584 NH2 ARG B 118 38. .367 35 .427 41, .376 1, .00 44, .09 7

ATOM 2585 C ARG B 118 34, ,215 35, .819 35, .332 1, ,00 42, ,68 6

ATOM 2586 O ARG B 118 34, .657 36, .604 34, .503 1. .00 43. .76 8

ATOM 2587 N GLN B 119 33 .324 36 .190 36, .239 1. ,00 41, ,50 7

ATOM 2588 CA GLN B 119 32 .815 37 .553 36 .229 1, .00 40 .73 6

ATOM 2589 CB GLN B 119 31, .817 37, .664 35, .080 1, .00 37, .47 6

ATOM 2590 CG GLN B 119 31, .199 39, .002 34. .850 1, .00 37, .63 6

ATOM 2591 CD GLN B 119 30 .414 39 .031 33, .553 1, .00 38, .05 6

ATOM 2592 OEl GLN B 119 29 .835 38 .028 33 .137 1 .00 40 .82 8

ATOM 2593 NE2 GLN B 119 30 .380 40 .181 32 .914 1 .00 38 .24 7

ATOM 2594 C GLN B 119 32 .171 37 .897 37, .561 1 .00 41 .65 6

ATOM 2595 O GLN B 119 31 .660 37 .028 38. .245 1, .00 43, .20 8

ATOM 2596 N ARG B 120 32 .208 39 .163 37 .945 1 .00 43 .19 7

ATOM 2597 CA ARG B 120 31 .606 39 .561 39 .209 1 .00 46 .59 6

ATOM 2598 CB ARG B 120 32 .500 40, .540 39, .955 1, .00 48, .44 6

ATOM 2599 CG ARG B 120 33 .874 40 .005 40 .232 1 .00 57 .79 6

ATOM 2600 CD ARG B 120 34 .423 40 .632 41 .493 1 .00 64 .95 6

ATOM 2601 NE ARG B 120 33 .964 39 .971 42 .727 1 .00 67 .80 7

ATOM 2602 CZ ARG B 120 33 .571 40 .624 43, .818 1 .00 68 .76 6

ATOM 2603 NHl ARG B 120 33, .565 41 .958 43, .827 1, .00 66, .34 7

ATOM 2604 NH2 ARG B 120 33 .219 39 .944 44 .913 1 .00 69 .34 7

ATOM 2605 C ARG B 120 30 .241 40 .184 38 .999 1 .00 45 .42 6

ATOM 2606 O ARG B 120 29 .991 40 .825 37 .979 1 .00 43 .82 8

ATOM 2607 N PHE B 121 29 .361 39 .983 39 .972 1 .00 45 .27 7

ATOM 2608 CA PHE B 121 28 .012 40 .515 39 .882 1 .00 46 .73 6

ATOM 2609 CB PHE B 121 26 .998 39 .411 39 .558 1 .00 44 .66 6

ATOM 2610 CG PHE B 121 27 .320 38 .639 38 .324 1 .00 41 .56 6

ATOM 2611 CDl PHE B 121 28 .265 37 .621 38 .355 1 .00 38, .98 6

ATOM 2612 CD2 PHE B 121 26 .698 38 .942 37 .123 1 .00 40, .65 6 ATOM 2613 CEl PHE B 121 28.,585 36.,920 37..212 1.,00 38.,44 6

ATOM 2614 CE2 PHE B 121 27. ,013 38. .245 35. .977 1. ,00 38. ,36 6

ATOM 2615 CZ PHE B 121 27. 959 37. ,232 36. ,020 1. 00 37. 80 6

ATOM 2616 C PHE B 121 27. ,549 41. ,193 41. .142 1. 00 47. 76 6

ATOM 2617 O PHE B 121 28. ,094 40. .972 42. .224 1. ,00 45. ,87 8

ATOM 2618 N SER B 122 26. 521 42. .021 40. .966 1. ,00 49. ,39 7

ATOM 2619 CA SER B 122 25. 881 42. ,735 42. .054 1. ,00 51. 30 6

ATOM 2620 CB SER B 122 25. .677 44, .200 41, .680 1. .00 50. ,63 6

ATOM 2621 OG SER B 122 25. ,026 44. .887 42, .726 1. ,00 52. ,75 8

ATOM 2622 C SER B 122 24. 530 42. ,041 42. ,235 1. 00 52. 14 6

ATOM 2623 O SER B 122 23. .659 42. ,135 41, .377 1. .00 51. ,12 8

ATOM 2624 N CYS B 123 24. ,371 41. ,323 43. .340 1, ,00 53. ,84 7

ATOM 2625 CA CYS B 123 23. .133 40, .605 43. .603 1, .00 56. ,99 6

ATOM 2626 C CYS B 123 22. .973 40, .343 45 .111 1, ,00 58, .94 6

ATOM 2627 O CYS B 123 23. .837 40, .727 45, .911 1. .00 58. .00 8

ATOM 2628 CB CYS B 123 23. ,135 39. ,282 42. .830 1. ,00 55. ,83 6

ATOM 2629 SG CYS B 123 24. ,561 38. ,231 43. .250 1. 00 57. 55 16

ATOM 2630 N ASP B 124 21. .874 39, ,687 45, .491 1. .00 59. .24 7

ATOM 2631 CA ASP B 124 21. .619 39. .412 46. .893 1. ,00 59. ,17 6

ATOM 2632 CB ASP B 124 20. .148 39. .085 47, .114 1. ,00 61. .47 6

ATOM 2633 CG ASP B 124 19. .670 39. .487 48, .505 1. ,00 62. ,03 6

ATOM 2634 ODl ASP B 124 20. .462 39, .403 49, .470 1. ,00 60. ,72 8

ATOM 2635 OD2 ASP B 124 18. .493 39, ,886 48. .628 1. ,00 63. .80 8

ATOM 2636 C ASP B 124 22, .470 38, .274 47, .434 1, .00 59. .25 6

ATOM 2637 O ASP B 124 22. .309 37, .122 47 .036 1. .00 58. .84 8

ATOM 2638 N VAL B 125 23, .365 38, .612 48, .356 1. .00 59. .36 7

ATOM 2639 CA VAL B 125 24, .260 37, .647 48, .979 1. .00 59, .62 6

ATOM 2640 CB VAL B 125 25. .683 38. .230 49. .080 1. ,00 57, ,35 6

ATOM 2641 CGI VAL B 125 26. .599 37. .280 49, .798 1. .00 54. .50 6

ATOM 2642 CG2 VAL B 125 26, .212 38, .519 47, .702 1. ,00 58. ,35 6

ATOM 2643 C VAL B 125 23, .766 37, .277 50, .378 1. ,00 62. ,42 6

ATOM 2644 O VAL B 125 24 .161 36, .254 50 .938 1, .00 64, .51 8

ATOM 2645 N SER B 126 22. ,892 38. ,105 50. ,939 1. ,00 63. ,61 7

ATOM 2646 CA SER B 126 22 .375 37 .857 52 .283 1, .00 64, .32 6

ATOM 2647 CB SER B 126 21, .260 38, .857 52 .613 1, ,00 63, .21 6

ATOM 2648 OG SER B 126 20 .175 38 .715 51 .715 1. .00 59, .22 8

ATOM 2649 C SER B 126 21 .858 36 .429 52 .444 1 .00 64, .47 6

ATOM 2650 O SER B 126 21 .082 35 .940 51 .626 1. .00 63, .31 8

ATOM 2651 N GLY B 127 22, .313 35, .764 53, .496 1, ,00 65. ,55 7

ATOM 2652 CA GLY B 127 21, .872 34. .409 53. .748 1. ,00 68, .84 6

ATOM 2653 C GLY B 127 22 .847 33 .351 53 .282 1, .00 70, .32 6

ATOM 2654 O GLY_.B 127 22. .634 32. .161 53 .500 1, .00 71, .17 8

ATOM 2655 N VAL B 128 23 .923 33 .776 52 .638 1, .00 71 .67 7

ATOM 2656 CA VAL B 128 24 .910 32 .826 52 .148 1, .00 72 .95 6

ATOM 2657 CB VAL B 128 26 .107 33 .522 51 .467 1. .00 71 .97 6

ATOM 2658 CGI VAL B 128 25 .686 34 .081 50 .149 1, .00 73, .72 6

ATOM 2659 CG2 VAL B 128 26 .654 34 .614 52 .359 1 .00 69 .90 6

ATOM 2660 C VAL B 128 25 .504 31 .942 53 .212 1 .00 73 .83 6

ATOM 2661 O VAL B 128 25 .628 30. .743 53 .016 1, .00 73, .27 8

ATOM 2662 N ASP B 129 25 .884 32 .542 54 .332 1 .00 75 .83 7

ATOM 2663 CA ASP B 129 26 .532 31 .789 55 .384 1 .00 78 .34 6

ATOM 2664 CB ASP B 129 27 .008 32 .715 56 .504 1, .00 79. .36 6

ATOM 2665 CG ASP B 129 ^■28 .209 32 .141 57 .257 1, .00 81, .22 6

ATOM 2666 ODl ASP B 129 29 .166 32 .909 57 .523 1 .00 81 .78 8

ATOM 2667 OD2 ASP B 129 28 .202 30 .922 57 .576 1 .00 81 .70 8

ATOM 2668 C ASP B 129 25 .720 30 .648 55 .972 1 .00 80 .31 6

ATOM 2669 O ASP B 129 26 .293 29 .783 56 .660 1 .00 81 .06 8

ATOM 2670 N THR B 130 24 .412 30 .603 55 .706 1 .00 80 .80 7

ATOM 2671 CA THR B 130 23 .640 29 .501 56 .259 1 .00 81 .78 6

ATOM 2672 CB THR B 130 23 .681 29 .563 57 .799 1 .00 85 .11 6

ATOM 2673 OG1 THR B 130 24 .158 30 .862 58 .195 1 .00 84 .93 8 ATOM 2674 CG2 THR B 130 24.,582 28..416 58..388 1.,00 85.,83 6

ATOM 2675 C THR B 130 22. 182 29. ,286 55. ,881 1. 00 80. 84 6

ATOM 2676 O THR B 130 21. ,460 30. .224 55. .506 1. ,00 78. ,93 8

ATOM 2677 N GLU B 131 21. 784 28. .014 56. .028 1. ,00 80. ,92 7

ATOM 2678 CA GLU B 131 20. 416 27. ,510 55. .832 1. ,00 80. ,70 6

ATOM 2679 CB GLU B 131 19. ,435 28. .339 .56. .689 1. ,00 83. ,05 6

ATOM 2680 CG GLU B 131 19. ,467 28. .017 58. .187 1. ,00 84. ,49 6

ATOM 2681 CD GLU B 131 19. ,024 29, .189 59. .051 1. ,00 85. ,34 6

ATOM 2682 OEl GLU B 131 17. ,948 29. ,773 58. ,762 1. ,00 86. ,44 8

ATOM 2683 OE2 GLU B 131 19. ,757 29. ,521 60. ,019 1. ,00 85. ,14 8

ATOM 2684 C GLU B 131 19. .864 27. .420 54, ,426 1. ,00 79. .07 6

ATOM 2685 O GLU B 131 20. .207 26. ,520 53. ,643 1. ,00^' 76. .96 8

ATOM 2686 N SER B 132 18, .941 28, .338 54, .156 1. .00 78. .17 7

ATOM 2687 CA SER B 132 18. .298 28, .449 52, .858 1. .00 77. ,92 6

ATOM 2688 CB SER B 132 16. .953 29, .195 53. .001 1. .00 77. .07 6

ATOM 2689 OG SER B 132 17. .130 30. ,486 53. .575 1. .00 77. .45 8

ATOM 2690 C SER B 132 19. .277 29. ,220 51. .945 1. ,00 76. .88 6

ATOM 2691 O SER B 132 19. ,000 29. .463 50. .759 1. ,00 77. .41 8

ATOM 2692 N <pΞLY B 133 20. .424 29, .588 52, ,520 1. ,00 74. .38 7

ATOM 2693 CA GLY B 133 21. .442 30 .308 51 .782 1. .00 72 .04 6

ATOM 2694 C GLY B 133 20. .943 31. .569 51. .105 1. ,00 71. .42 6

ATOM 2695 O ^'GLY B 133 19 .888 32 .104 51 .450 1 .00 71 .39 8

ATOM 2696 N ALA B 134 21, .708 32, .044 50. .125 1, ,00 69. .68 7

ATOM 2697 CA ALA B 134 21. .345 33. ,251 49. ,390 1. ,00 66, .69 6

ATOM 2698 CB ALA B 134 22, .534 34 .194 49 .315 1, .00 66 .34 6

ATOM 2699 C ALA B 134 20, .874 32, .908 47. .993 1, .00 64. .53 6

ATOM 2700 O ALA B 134 21, .095 31, .802 47, ,504 1, .00 64, .56 8

ATOM 2701 N THR B 135 20 .207 33 .865 47, .369 1, .00 62 .63 7

ATOM 2702 CA THR B 135 19, .719 33, .696 46. .017 1. .00 62, .23 6

ATOM 2703 CB THR B 135 18, .205 33, .577 45. .980 1. .00 62, .17 6

ATOM 2704 OG1 THR B 135 17 .812 32, .456 46, .775 1. .00 64, .85 8

ATOM 2705 CG2 THR B 135 17, .721 33, .370 44, ,543 1. .00 62, .33 6

ATOM 2706 C THR B 135 20, .159 34, .900 45. .194 1. .00 62, .39 6

ATOM 2707 O THR B 135 19 .618 36 .009 45 .308 1 .00 62 .56 8

ATOM 2708 N CYS B 136 21 .174 34, .661 44, .379 1, .00 61 .14 7

ATOM 2709 CA CYS B 136 21 .754 35, .668 43, .526 1, .00 58 .61 6

ATOM 2710 C CYS B 136 21 .159 35 .497 42 .134 1 .00 56 .85 6

ATOM 2711 O CYS B 136 21. .308 34, .452 41, .503 1. .00 55, .78 8

ATOM 2712 CB CYS B 136 23 .276 35, .474 43, .527 1, .00 58 .82 6

ATOM 2713 SG CYS B 136 24 .201 36 .455 42 .315 1 .00 60 .36 16

ATOM 2714 N ARG B 137 20 .453 36 .519 41, .670 1 .00 55 .98 7

ATOM 2715 CA ARG B 137 1 .845 36 .457 40, .353 1 . 00 56 .14 6

ATOM 2716 CB ARG B 137 18 .421 37 .009 40 .383 1 .00 57 .73 6

ATOM 2717 CG ARG B 137 17 .502 36, .250 41, .303 1, .00 62 .21 6

ATOM 2718 CD ARG B 137 16 .367 37, .136 41. .792 1, .00 68 .77 6

ATOM 2719 NE ARG B 137 15 .827 36 .666 43, .071 1 .00 74 .27 7

ATOM 2720 CZ ARG B 137 15 .070 35, .575 43, .224 1, .00 76 .32 6

ATOM 2721 NHl ARG B 137 14 .739 34 .822 42 .174 1 .00 77 .05 7

ATOM 2722 NH2 ARG B 137 14 .652 35 .221 44 .434 1 .00 75 .79 7

ATOM 2723 C ARG B 137 20 .672 37 .253 39, .366 1, .00 55 .38 6

ATOM 2724 O ARG B 137 21 .052 38 .389 39, .637 1, .00 57 .67 8

ATOM 2725 N ILE B 138 20 .933 36. .646 38. ,215 1, .00 52 .27 7

ATOM 2726 CA ILE B 138 21 .716 37 .255 37 .163 1 .00 48 .96 6

ATOM 2727 CB ILE B 138 22 .977 36 .411 36, .890 1 .00 45 .32 6

ATOM 2728 CG2 ILE B 138 23 .751 37 .007 35 .749 1 .00 42 .82 6

ATOM 2729 CGI ILE B 138 23 .822 36 .309 38 .160 1 .00 42 .90 6

ATOM 2730 CDl ILE B 138 24 .931 35 .313 38. .067 1 .00 40 .32 6

ATOM 2731 C ILE B 138 20 .863 37 .313 35, .900 1 .00 48 .66 6

ATOM 2732 O ILE B 138 20 .420 36 .286 35, .406 1 .00 49 .73 8

ATOM 2733 N LYS B 139 20 .628 38. .506 35, .375 1 .00 48 .12 7

ATOM 2734 CA LYS B 139 19 .822 38 .642 34 .165 1 .00 51 .18 6 ATOM 2735 CB LYS B 139 18.775 39..759 34..326 1.00 52..93 6

ATOM 2736 CG LYS B 139 17. 908 39. ,625 35. ,553 1. 00 56. ,09 6

ATOM 2737 CD LYS B 139 16. 721 40. ,567 35. ,523 1. 00 58. ,54 6

ATOM 2738 CE LYS B 139 15. ,716 40. .155 34. .461 1. 00 59. ,19 6

ATOM 2739 NZ LYS B 139 14. 539 41. ,062 34, ,435 1. 00 59. ,74 7

ATOM 2740 C LYS B 139 20. ,686 38. ,966 32, .957 1. 00 50. ,79 6

ATOM 2741 O LYS B 139 21. ,461 39. ,919 32. .998 1. 00 53. ,10 8

ATOM 2742 N ILE B 140 20. ,561 38. ,192 31, ,883 1. ,00 47. ,96 7

ATOM 2743 CA ILE B 140 21. ,348 38. ,480 30. ,696 1. 00 49. ,36 6

ATOM 2744 CB ILE B 140 22. 590 37. ,531 30, ,607 1. 00 49. . 96 6

ATOM 2745 CG2 ILE B 140 23. .254 37. .411 31. ,973 1. 00 52. ,22 6

ATOM 2746 CGI ILE B 140 22. ,192 36. ,126 30. ,217 1. 00 50. ,93 6

ATOM 2747 CDl ILE B 140 23. ,312 35. ,115 30. ,483 1. 00 54. ,24 6

ATOM 2748 C ILE B 140 20. .520 38. ,444 29. ,410 1. 00 48. ,36 6

ATOM 2749 O ILE B 140 19. .727 37, .545 29, .211 1. ,00 49. ,73 8

ATOM 2750 N GLY B 141 20. .685 39, ,448 28, .557 1. ,00 46. .46 7

ATOM 2751 CA GLY B 141 19. .941 39. .500 27 .313 1. ,00 47, .33 6

ATOM 2752 C GLY B 141 20, .631 40, .387 26. .293 1. .00 46, .71 6

ATOM 2753 O GLY B 141 21. .623 41. .025 26, .625 1. ,00 47, .72 8

ATOM 2754 N SER B 142 20 .131 40 .425 25 .058 1, .00 45 .43 7

ATOM 2755 CA SER B 142 20, .739 41, .267 24 .026 1. ,00 44, .63 6

ATOM 2756 CB SER B 142 19 .990 41 .165 22 .706 1. .00 42 .45 6

ATOM 2757 OG SER B 142 20, .431 42, .168 21, .814 1. .00 40, .68 8

ATOM 2758 C SER B 142 20, .774 42, .728 24 .457 1. .00 46, .01 6

ATOM 2759 O SER B 142 19. .812 43, .256 25 .031 1. ,00 46 .34 8

ATOM 2760 N TRP B 143 21. .888 43. .384 24, .162 1. .00 46, .69 7

ATOM 2761 CA TRP B 143 22, .069 44. ,761 24 .549 1. .00 45, .07 6

ATOM 2762 CB TRP B 143 23, .553 45, .044 24, .758 1. ,00 44. .45 6

ATOM 2763 CG TRP B 143 23, .816 46 .368 25, .388 1. .00 43. .71 6

ATOM 2764 CD2 TRP B 143 23 .642 46 .697 26 .762 1. .00 40 .44 6

ATOM 2765 CΞ2 TRP B 143 23, .999 48, .055 26, .920 1. .00 40, .05 6

ATOM 2766 CE3 TRP B 143 23 .221 45 .975 27 .880 1. ,00 38 .96 6

ATOM 2767 CDl TRP B 143 24, .262 47, .517 24 .773 1. .00 43, .74 6

ATOM 2768 NEl TRP B 143 24 .373 48 .534 25 .691 1. .00 40 .21 7

ATOM 2769 CZ2 TRP B 143 23, .947 48, .694 28, .149 1. ,00 38, .81 6

ATOM 2770 CZ3 TRP B 143 23 .171 46, .612 29 .097 1, ,00 35, .11 6

ATOM 2771 CH2 TRP B 143 23 .531 47, .956 29 .224 1, ,00 37 .51 6

ATOM 2772 C TRP B 143 21, .499 45, ,730 23, .545 1. ,00 46, .35 6

ATOM 2773 O TRP B 143 21 .062 46 .813 23 .909 1, .00 48 .58 8

ATOM 2774 N THR B 144 21, .477 45, .358 22 .277 1. .00 45. .22 7

ATOM 2775 CA THR B 144 20 .963 46 .287 21 .290 1 .00 45 .21 6

ATOM 2776 CB THR B 144 22 .072 46 .696 20 .328 1. .00 44 .02 6

ATOM 2777 OG1 THR B 144 22 .669 45 .524 19 .763 1, .00 4 .19 8

ATOM 2778 CG2 THR B 144 23 .129 47 .487 21 .069 1, .00 42 .50 6

ATOM 2779 C THR B 144 19 .778 45 .793 20 .485 1, .00 48 .06 6

ATOM 2780 O THR B 144 19 .136 46 .576 19 .783 1. .00 50 .29 8

ATOM 2781 N HIS B 145 19 .474 44 .504 20 .584 1, .00 47 .78 7

ATOM 2782 CA HIS B 145 18 .364 43 .970 19 .820 1, . 00 48 .99 6

ATOM 2783 CB HIS B 145 18 .800 42 .716 19 .055 1, .00 47 .81 6

ATOM 2784 CG HIS B 145 19 .805 42 .974 17 .974 1 .00 46 .09 6

ATOM 2785 CD2 HIS B 145 19 .677 43 .532 16 .748 1, .00 44 .37 6

ATOM 2786 NDl HIS B 145 21 .125 42, .602 18 .086 1. .00 45 .57 7

ATOM 2787 CEl HIS B 145 •21 .766 42 .915 16 .975 1, .00 44 .33 6

ATOM 2788 NE2 HIS B 145 20 .909 43 .481 16 .146 1, .00 41 .88 7

ATOM 2789 C HIS B 145 17 .149 43 .656 20 .682 1, .00 50 .77 6

ATOM 2790 O HIS B 145 17 .235 42 .933 21 .668 1. .00 52 .14 8

ATOM 2791 N HIS B 146 16 .010 44 .213 20 .302 1, .00 52 .05 7

ATOM 2792 CA HIS B 146 14 .774 43 .974 21 .027 1 .00 54 .32 6

ATOM 2793 CB HIS B 146 13 .797 45 .130 20 .800 1. .00 52 .48 6

ATOM 2794 CG HIS B 146 13 .526 45 .413 19 .360 1 .00 52 .25 6

ATOM 2795 CD2 HIS B 146 13 .106 44 .605 18 .357 1 .00 53 .49 6 ATOM 2796 NDl HIS B 146 13.726 46.,653 18..795 1.,00 53.,68 7

ATOM 2797 CEl HIS B 146 13. 448 46. ,597 17. .504 1. ,00 55. ,84 6

ATOM 2798 NE2 HIS B 146 13. ,070 45. ,364 17. .212 1. ,00 55. .30 7

ATOM 2799 C HIS B 146 14. 149 42. ,647 20. ,576 1. ,00 57. .05 6

ATOM 2800 O HIS B 146 14. 640 41. ,984 19. ,644 1. ,00 58. .04 8

ATOM 2801 N SER B 147 13. 057 42. 280 21. ,243 1. ,00 58. ,47 7

ATOM 2802 CA SER B 147 12. .328 41. ,037 20. ,997 1. ,00 58. .52 6

ATOM 2803 CB SER B 147 11. ,071 41. .021 21, .861 1. .00 58. ,93 6

ATOM 2804 OG SER B 147 10. ,386 42. ,252 21, ,740 1. .00 63. .53 8

ATOM 2805 C SER B 147 11. ,955 40. ,708 19. .557 1. ,00 57. .13 6

ATOM 2806 O SER B 147 11. 776 39. 545 19, ,215 1. ,00 56. ,86 8

ATOM 2807 N ARG B 148- 11. ,841 41. ,716 18. .709 1. .00 56. .50 7

ATOM 2808 CA ARG B 148 11. ,473 41. ,462 17. .323 1. ,00 58. ,81 6

ATOM 2809 CB ARG B 148 10. ,905 42. ,734 16, .691 1. ,00 62. .56 6

ATOM 2810 CG ARG B 148 9. .781 43. .380 17. .493 1. .00 70, ,38 6

ATOM 2811 CD ARG B 148- 9. .337 44. .731 16, .897 1. .00 76, ,49 6

ATOM 2812 NE ARG B 148 8. .480 45. .487 17, ,819 1. ,00 82. .57 7

ATOM 2813 CZ ARG B 148 7. ,263 45. .104 18, .222 1, ,00 84, .74 6

ATOM 2814 NHl ARG B 148 6. ,728 43. .965 17, .791 1. .00 85. .52 7

ATOM 2815 NH2 ARG B 148 6, ,573 45. ,864 19 .064 1. .00 85, .55 7

ATOM 2816 C ARG B 148 12, .655 40. ,963 16, .490 1. ,00 57, .83 6

ATOM 2817 0 ARG B 148 12, .474 40, .423 15 .395 1. .00 58 .23 8

ATOM 2818 N GLU B 149 13, .864 41, .147 17 .011 1, .00 56, .99 7

ATOM 2819 CA GLU B 149 15 .072 40, .743 16 .306 1, .00 53 .60 6

ATOM 2820 CB GLU B 149 16 .015 41, .933 16 .216 1, .00 52 .91 6

ATOM 2821 CG GLU B 149 15, .280 43, .243 15 .955 1, .00 51, .82 6

ATOM 2822 CD GLU B 149 16. ,208 44. ,437 15, .841 1. .00 54, .76 6

ATOM 2823 OEl GLU B 149 17, .132 44. ,562 16 .672 1, .00 55 .52 8

ATOM 2824 OE2 GLU B 149 16 .010 45 .261 14 .929 1 .00 52 .75 8

ATOM 2825 C GLU B 149 15, .729 39, .584 17 .036 1, .00 52 .38 6

ATOM 2826 O GLU B 149 16, .150 38, ,606 16. .421 1, .00 51 .81 8

ATOM 2827 N ILE B 150 15 .811 39, .693 18, .355 1. .00 51, .32 7

ATOM 2828 CA ILE B 150 16. .382 38, .619 19 .154 1, .00 51 .11 6

ATOM 2829 CB ILE B 150 17, .770 38, .989 19, .757 1, .00 48, .77 6

ATOM 2830 CG2 ILE B 150 18, .155 37, .995 20, .843 1. ,00 43, .40 6

ATOM 2831 CGI ILE B 150 18 .842 38, .967 18, .672 .1, .00 47, .30 6

ATOM 2832 CDl ILE B 150 20 .219 39, .315 19 .168 1 .00 45 .12 6

ATOM 2833 C ILE B 150 15 .453 38, .254 20 .297 1, .00 53 .02 6

ATOM 2834 O ILE B 150 14, .842 39. .116 20, .932 1, .00 52, .00 8

ATOM 2835 N SER B 151 15 .350 36, .955 20 .539 1, .00 55 .16 7

ATOM 2836 CA SER B 151 14 .542 36 .436 21 .628 1 .00 56 .52 6

ATOM 2837 CB SER B 151 13 .280 35. .733 21 .089 1, .00 57 .06 ^' 6

ATOM 2838 OG SER B 151 13 .594 34 .585 20 .323 1 .00 54 .91 8

ATOM 2839 C SER B 151 15 .452 35 .447 22 .337 1. .00 56 .69 6

ATOM 2840 O SER B 151 16 .144 34 .676 21 .685 1 .00 57 .55 8

ATOM 2841 N VAL B 152 15 .480 35 .504 23 .661 1 .00 58 .35 7

ATOM 2842 CA VAL B 152 16 .306 34 .600 24 .456 1, .00 60 .89 6

ATOM 2843 CB VAL B 152 17 .135 35 .362 25 .502 1 .00 60 .77 6

ATOM 2844 CGI VAL B 152 17 .890 36 .489 24 .844 1 .00 59 .09 6

ATOM 2845 CG2 VAL B 152 16 .220 35 .903 26 .586 1 .00 62 .75 6

ATOM 2846 C VAL B 152 15 .389 33 .632 25 .194 1 .00 62 .80 6

ATOM 2847 O VAL B 152 14 .287 34 .012 25 .597 1 .00 63 .08 8

ATOM 2848 N ASP B 153 15 .845 32 .395 25 .387 1 .00 64 .20 7

ATOM 2849 CA ASP B 153 15 .028 31 .390 26 .061 1 .00 66 .36 6

ATOM 2850 CB ASP B 153 14 .232 30 .611 25 .016 1 .00 67 .03 6

ATOM 2851 CG ASP B 153 13 .427 31 .518 24 .095 1 .00 68 .33 6

ATOM 2852 ODl ASP B 153 12 .327 31 .949 24 .504 1 .00 65 .39 8

ATOM 2853 OD2 ASP B 153 13 .905 31 .810 22 .969 1 .00 70 .09 8

ATOM 2854 C ' ASP B 153 15 .877 30 .416 26 .872 1 .00 68 .77 6

ATOM 2855 O ASP B 153 16 .974 30 .049 26 .453 1 .00 69 .28 8

ATOM 2856 N PRO B 154 15 .404 30 .017 28 .067 1 .00 70 .46 7 -liy

ATOM 2857 CD PRO B 154 14.409 30. 740 28. 876 1. 00 69 . 92 6

ATOM 2858 CA PRO B 154 16. 157 29. .070 28. .898 1. 00 72. ,29 6

ATOM 2859 CB PRO B 154 15. 410 29. ,108 30. ,225 1. 00 70. 76 6

ATOM 2860 CG PRO B 154 14. 902 30. .494 30. .281 1. ,00 69. ,28 6

ATOM 2861 C PRO B 154 16. .151 27. ,668 28. ,250 1. 00 75. ,71 6

ATOM 2862 O PRO B 154 15. ,548 27, .467 27. .187 1. ,00 75. .41 8

ATOM 2863 N THR B 155 16. ,807 26. .700 28, ,888 1. ,00 79. ,33 7

ATOM 2864 CA THR B 155 16. 887 25. ,350 28. .332 1. ,00 83, .13 6

ATOM 2865 CB THR B 155 18. .208 25. .187 27. .542 1. ,00 82. .37 6

ATOM 2866 OG1 THR B 155 19. .316 25. .233 28, ,453 1. ,00 83. .94 8

ATOM 2867 CG2 THR B 155 18. ,378 26, .311 26, .545 1. ,00 81. .49 6

ATOM 2868 C THR B 155 16. ,785 24. ,189 29, ,348 1. ,00 86. ,65 6

ATOM 2869 O THR B 155 16. ,122 24, ,298 30, .385 1. ,00 87. .45 8

ATOM 2870 N THR B 156 17. ,452 23, .078 29. .013 1. ,00 90. ,57 7

ATOM 2871 CA THR B 156 17. .504 21, .839 29. .813 1. ,00 93. .48 6

ATOM 2872 CB THR B 156 18. ,799 21. .025 29. ,491 1. 00 93. ,70 6

ATOM 2873 OG1 THR B 156 18. ,861 20. ,761 28. ,077 1. 00 92. ,52 8

ATOM 2874 CG2 THR B 156 18. ,825 19, .694 30, .301 1. ,00 93. ,12 6

ATOM 2875 C THR B 156 17. ,448 22, .012 31. .337 1. ,00 95. ,82 6

ATOM 2876 O THR B 156 18. .471 22. ,286 31, .990 1. ,00 95. ,51 8

ATOM 2877 N GLU B 157 16. .257 21. .809 31. ,897 1. 00 98. ,15 7

ATOM 2878 CA GLU B 157 16. .047 21, .946 33. .337 1. .00100, .26 6

ATOM 2879 CB GLU B 157 14. .583 22, .308 33, ,606 1. ,00102. .01 6

ATOM 2880 CG GLU B 157 14. .023 23. .363 32. .643 1. 00104. ,88 6

ATOM 2881 CD GLU B 157 12. ,539 23, ,649 32, .902 1. ,00106. .35 6

ATOM 2882 OEl GLU B 157 11. .745 22, .665 32, .965 1. ,00106. .79 8

ATOM 2883 OE2 GLU B 157 12, .178 24 .850 33, .030 1. ,00105, .97 8

ATOM 2884 C GLU B 157 16, .397 20, .662 34, .102 1. ,00100, ,31 6

ATOM 2885 O GLU B 157 16, ,352 20, .631 35, .348 1. ,00100, .47 8

ATOM 2886 N ASN B 158 16. .726 19 .601 33 .364 1. .00 99, .66 7

ATOM 2887 CA ASN B 158 17, ,065 18, .329 34, .003 1. ,00 99, ,04 6

ATOM 2888 CB ASN B 158 17, ,084 ^' 17, .198 32, . 969 1. .00100, .65 6

ATOM 2889 CG ASN B 158 15, .793 17, .113 32, .170 1. ,00101. .63 6

ATOM 2890 ODl ASN B 158 1 .701 16 .919 32 .733 1. ,00101, .77 8

ATOM 2891 ND2 ASN B 158 15, .909 17, .254 30, .847 1. .00102, .28 7

ATOM 2892 C ASN B 158 18, .439 18 .424 34 .672 1, .00 97, .31 6

ATOM 2893 O ASN B 158 18 .546 18 .748 35, .872 1. ,00 97, .45 8

ATOM 2894 N SER B 159 19, .473 18, .120 33, .881 1. .00 94, .36 7

ATOM 2895 CA SER B 159 20 .879 18 .156 34 .300 1, .00 90, .64 6

ATOM 2896 CB SER B 159 21. .645 19 .051 33, .325 1. ,00 91, .05 6

ATOM 2897 OG SER B 159 20 .831 20, .167 32, .948 1, .00 91, .42 8

ATOM 2898 C SER B 159 21. .129 18 .622 35 .742 1. .00 87 .58 6

ATOM 2899 O SER B 159 20 .770 19 .741 36 .114 1, .00 87 .04 8

ATOM 2900 N ASP B 160 21 .744 17 .767 36 .553 1. .00 84, .29 7

ATOM 2901 CA ASP B 160 22 .035 18, .137 37, .938 1, ,00 80, .73 6

ATOM 2902 CB ASP B 160 23 .003 17 .149 38 .582 1, .00 79 .96 6

ATOM 2903 CG ASP B 160 23 .404 17 .566 39 .991 1. ,00 79, .90 6

ATOM 2904 ODl ASP B 160 2 .459 17 .087 40 .471 1, ,00 79 .39 8

ATOM 2905 OD2 ASP B 160 22 .659 18 .362 40. .617 1. .00 79, .13 8

ATOM 2906 C ASP B 160 22 .687 19 .514 37 .956 1, .00 79 .03 6

ATOM 2907 O ASP B 160 23 .782 19 .687 37 .394 1, .00 78 .08 8

ATOM 2908 N ASP B 161 22 .022 20 .473 38 .612 1 .00 76 .06 7

ATOM 2909 CA ASP B 161 22 .506 21 .851 38 .706 1 .00 71 .50 6

ATOM 2910 CB ASP B 161 21 .655. 22 .683 39 .675 1 .00 70 .10 6

ATOM 2911 CG ASP B 161 20 .275 22 .977 39 .130 1 .00 69 .41 6

ATOM 2912 ODl ASP B 161 20 .140 23 .189 37 .905 1 .00 68 .26 8

ATOM 2913 OD2 ASP B 161 19 .319 23 .007 39 .929 1 .00 71 .44 8

ATOM 2914 C ASP B 161 23 .957 21 .979 39 .110 1 .00 69 .84 6

ATOM 2915 O ASP B 161 24 .569 23 .008 38 .843 1, .00 71 .09 8

ATOM 2916 N SER B 162 24 .527 20 .960 39 .740 1 .00 67 .23 7

ATOM 2917 CA SER B 162 25 .928 21 .078 40 .136 1 .00 67 .27 6 ATOM 2918 CB SER B 162 26.,051 21.,210 41..661 1..00 67..18 6

ATOM 2919 OG SER B 162 25. 648 20. ,020 42. ,315 1. 00 66. ,16 8

ATOM ^<-^' 2920 C SER B 162 26. ,787 19. .922 39. .653 1. ,00 66. .71 6

ATOM 2921 O SER B 162 27. ,786 19. .576 40. ,289 1. ,00 64. .25 8

ATOM 2922 N GLU B 163 26. ,410 19. .330 38, ,523 1. ,00 67. .10 7

ATOM 2923 CA GLU B 163 27. ,192 18, ,220 38. .005 1. ,00 68. .36 6

ATOM 2924 CB GLU B 163 26. ,378 17, ,421 36. ,970 1. ,00 70, ,98 6

ATOM 2925 CG GLU B 163 26. .411 17, .926 35. .545 1, .00 72, .60 6

ATOM 2926 CD GLU B 163 25. ,726 16. ,946 34. ,594 1. .00 74. ,62 6

ATOM 2927 OEl GLU B 163 24. ,477 16. .828 34, ,649 1. ,00 76, .45 8

ATOM 2928 OE2 GLU B 163 26. .428 16, .285 33. .798 1. .00 74, .37 8

ATOM 2929 C GLU B 163 28, .530 18 .688 37, .410 1, .00 67 .51 6

ATOM 2930 O GLU B 163 29, ,379 17. .868 37. ,070 1. .00 67, ,13 8

ATOM 2931 N TYR B 164 28. .709 20, .008 37. .294 1. ,00 66. .57 7

ATOM 2932 CA TYR B 164 29, .943 20, .583 36, ,771 1, .00 64 .39 6

ATOM 2933 CB TYR B 164 29, .671 21. .419 35. .526 1, .00 64, .28 6

ATOM 2934 CG TYR B 164 29, .192 20. .602 34, ,354 1. ,00 66, .44 6

ATOM 2935 CDl TYR B 164 27, .948 20, .860 33, ,766 1, ,00 66, .70 6

ATOM 2936 CEl TYR B 164 27 .490 20 .105 32 .690 1. .00 66 .59 6

ATOM 2937 CD2 TYR B 164 29, ,973 19, .556 33. ,832 1, .00 65, .02 6

ATOM 2938 CE2 TYR B 164 29, ,524 18, .790 32. ,756 1. .00 65, .71 6

ATOM 2939 CZ TYR B 164 28, .277 19 .075 32, .184 1, .00 66, .77 6

ATOM 2940 OH TYR B 164 27, .819 18, .369 31, .084 1, .00 67, .83 8

ATOM 2941 C TYR B 164 30, .584 21, .463 37, .826 1, .00 63, .28 6

ATOM 2942 O TYR B 164 31, .717 21, .936 37, .662 1, .00 61, .67 8

ATOM 2943 N PHE^' B 165 29 .859 21 .673 38 .918 1, .00 61 .88 7

ATOM 2944 CA PHE B 165 30, .357 22, .517 39, .990 1, ,00 60, .70 6

ATOM 2945 CB PHE B 165 29, .288 22, .704 41, ,067 1. .00 58, ,78 6

ATOM 2946 CG PHE B 165 29 .523 23 .905 41, .941 1, .00 57 .08 6

ATOM 2947 CDl PHE B 165 29 .420 25 .184 41, .413 1, .00 56, .05 6

ATOM 2948 CD2 PHE B 165 29, .888 23 .757 43, .272 1, .00 54, .09 6

ATOM 2949 CEl PHE B 165 29 .680 26 .296 42, .200 1, .00 55, .95 6

ATOM 2950 CE2 PHE B 165 30 .149 24 .858 44 .063 1, .00 55 .48 6

ATOM 2951 CZ PHE B 165 30, .048 26, .131 43, .530 1, .00 56, .15 6

ATOM 2952 C PHE B 165 31, .626 21, .960 40, .614 1. ,00 59, .91 6

ATOM 2953 O PHE B 165 31 .757 20 .760 40 .808 1, .00 60 .17 8

ATOM 2954 N SER B 166 32 .572 22 .839 40, .919 1, .00 60 .28 7

ATOM 2955 CA SER B 166 33 .807 22 .390 41, .532 1, .00 60 .24 6

ATOM 2956 CB SER B 166 34 .810 23 .534 41, .647 1, .00 59 .33 6

ATOM 2957 OG SER B 166 36 .012 23 .081 42 .239 1 .00 59 .12 8

ATOM 2958 C SER B 166 33 .468 21 .877 42, ,916 1, .00 60, .82 6

ATOM 2959 O SER B 166 32 .614 22, .434 43, .611 1, .00 60, .12 8

ATOM 2960 N GLN B 167 34 .148 20 .815 43, .319 1, .00 61 .73 7

ATOM 2961 CA GLN B 167 33 .907 20 .228 44, .623 1, .00 62 .29 6

ATOM 2962 CB GLN B 167 34 .228 18 .737 44, .576 1, .00 63 .96 6

ATOM 2963 CG GLN B 167 35 .620 18, .442 44, .068 1, .00 66 .77 6

ATOM 2964 CD GLN B 167 35 .827 16 .969 43 .736 1 .00 68 .16 6

ATOM 2965 OEl GLN B 167 35 .710 16, .103 44, .605 1. .00 66, .24 8

ATOM 2966 NE2 GLN B 167 36 .136 16, .682 42, .465 1. .00 68, .10 7

ATOM 2967 C GLN B 167 34 .740 20 .912 45 .689 1, .00 60 .72 6

ATOM 2968 O GLN B 167 34 .433 20 .814 46 .880 1, .00 62 .24 8

ATOM 2969 N TYR B 168 35 .778 21 .626 45, .269 1, .00 57 .81 7

ATOM 2970 CA TYR B 168 ^•36 .637 22 .291 46, .235 1, .00 56 .47 6

ATOM 2971 CB TYR B 168 38 .078 22 .236 45 .741 1 .00 55 .55 6

ATOM 2972 CG TYR B 168 38 .457 20 .836 45, .330 .1, .00 55, .77 6

ATOM 2973 CDl TYR B 168 38 .420 20, .447 43, .988 1. .00 53, .38 6

ATOM 2974 CEl TYR B 168 38 .698 19 .139 43 .617 1, .00 53 .39 6

ATOM 2975 CD2 TYR B 168 38 .785 19 .872 46 .286 1, .00 55 .32 6

ATOM 2976 CE2 TYR B 168 39 .060 18 .561 45 .922 1, .00 54 .41 6

ATOM 2977 CZ TYR B 168 39 .013 18 .207 44 .591 1, .00 54 .89 6

ATOM 2978 OH TYR B 168 39 .270 16 .919 44 .227 1 .00 56 .81 8 ATOM 2979 C TYR B 168 36.222 23.712 46.586 1.00 55.31 6

ATOM 2980 O TYR B 168 36. 891 24. 395 47. 356 1. 00 54. 88 8

ATOM 2981 N SER B 169 35. 097 24. 140 46. 033 1. 00 55. 16 7

ATOM 2982 CA SER B 169 34. 570 25. 469 46. 299 1. 00 57. 04 6

ATOM 2983 CB SER B 169 33. 363 25. 755 45. 412 1. 00 55. 22 6

ATOM 2984 OG SER B 169 32. 775 26. ,991 45. ,769 1. ,00 55. ,21 8

ATOM 2985 C SER B 169 34. 147 25. 617 47. 754 1. 00 60 . 21 6

ATOM 2986 O SER B 169 33. ,664 24. .671 48. ,380 1. .00 62. ,02 8

ATOM 2987 N ARG B 170 34. 321 26. ,815 48. 298 1. ,00 61. ,79 7

ATOM 2988 CA ARG B 170 33. ,938 27, .059 49. ,678 1. .00 60. .59 6

ATOM 2989 CB ARG B 170 34. ,467 28. ,417 50. ,150 1. ,00 61. ,26 6

ATOM 2990 CG ARG B 170 35. ,781 28. ,342 50. ,904 1. ,00 61. ,61 6

ATOM 2991 CD ARG B 170 36. .588 29. ,628 50. ,764 1. ,00 66. .75 6

ATOM 2992 NE ARG B 170 35. ,866 30. .846 51. ,158 1. ,00 69. .32 7

ATOM 2993 CZ ARG B 170 35, .634 31. .877 50. .342 1, .00 68, ,59 6

ATOM 2994 NHl ARG B 170 36. .053 31. .840 49. .079 1. .00 65. ,59 7

ATOM 2995 NH2 ARG B 170 35. .017 32. .959 50, .803 1. .00 69, .04 7

ATOM 2996 C ARG B 170 32. .431 27. .041 49. ,785 1, ,00 58. ,91 6

ATOM 2997 0 ARG B 170 31. .892 26. .981 50. ,883 1, ,00 61. ,10 8

ATOM 2998 N PHE B 171 31, ,748 27, .077 48. ,650 1, .00 56, ,02 7

ATOM 2999 CA PHE B 171 30. .294 27. .093 48, .674 1. .00 56. ,85 6

ATOM 3000 CB PHE B 171 29, .782 28 .384 48, .033 1, .00 56, .79 6

ATOM 3001 CG PHE B 171 30, .498 29, .608 48, .529 1, .00 59, .30 6

ATOM 3002 CDl PHE B 171 31 .806 29 .889 48 .110 1, .00 59 .59 6

ATOM 3003 CD2 PHE B 171 29, .900 30, .447 49, .462 1, .00 58, .28 6

ATOM 3004 CEl PHE B 171 32, .497 30, .983 48, .616 1, .00 58, .87 6

ATOM 3005 CE2 PHE B 171 30 .586 31 .546 49 .978 1 .00 57 .19 6

ATOM 3006 CZ PHE B 171 31 .883 31, .817 49, .556 1, .00 58, .74 6

ATOM 3007 C PHE B 171 29 .694 25 .892 47 .987 1 .00 57 .50 6

ATOM 3008 O PHE B 171 30 .412 25 .063 47 .439 1, .00 57, .83 8

ATOM 3009 N GLU B 172. 28 .372 25 .793 48 .036 1 .00 58 .25 7

ATOM 3010 CA GLU B 172 27. .671 24, ,681 47, ,416 1. .00 58. ,95 6

ATOM 3011 CB GLU B 172 27 .418 23, .555 48, .436 1, .00 61, ,94 6

ATOM 3012 CG GLU B 172 26 .521 23 .921 49 .634 1 .00 65 .83 6

ATOM 3013 CD GLU B 172 26, .352 22, .769 50, .637 1, .00 67, .36 6

ATOM 3014 OEl GLU B 172 26 .275 21 .593 50 .192 1 .00 67 .12 8

ATOM 3015 OE2 GLU B 172 26 .280 23, .043 51, .868 1, .00 67, .97 8

ATOM 3016 C GLU B 172 26 .369 25 .197 46 .844 1 .00 59 .12 6

ATOM 3017 0 GLU B 172 25 .837 26 .217 47 .302 1 .00 58 .48 8

ATOM 3018 N ILE B 173 25 .865 24 .502 45 .831 1 .00 59 .47 7

ATOM 3019 CA ILE B 173^' 24 .630 24 .911 45 .180 1 .00 60 .85 6

ATOM 3020 CB ILE B 173 24 .715 24 .729 43 .653 1 .00 62 .04 6

ATOM 3021 CG2 ILE B 173 23 .369 25 .077 42 .998 1 .00 60 .25 6

ATOM 3022 CGI ILE B 173 25 .832 25 .603 43 .087 1 .00 62 .02 6

ATOM 3023 CDl ILE B 173 26 .018 25 .413 41 .600 1 .00 63 .88 6

ATOM 3024 C ILE B 173 23 .415 24 .148 45 .667 1 .00 61 .72 6

ATOM 3025 O ILE B 173 23 .415 22 .919 45 .733 1 .00 61 .55 8

ATOM 3026 N LEU B 174 22 .369 24 .883 45 .999 1 .00 62 .91 7

ATOM 3027 CA LEU B 174 21 .158 24 .253 46 .460 1 .00 63 .63 6

ATOM 3028 CB LEU B 174 20 .438 25 .166 47 .443 1 .00 63 .66 6

ATOM 3029 CG LEU B 174 21 .339 25 .698 48 .556 1 .00 64 .21 6

ATOM 3030 CDl LEU B 174 20 .543 26 .678 49 .428 1 .00 63 .13 6

ATOM 3031 CD2 LEU B 174 ■21 .914 24 .532 49 .369 1 .00 61 .09 6

ATOM 3032 C LEU B 174 20 .307 24 .010 45 .232 1 .00 64 .20 6

ATOM 3033 O^' LEU B 174 19 .891 22 .885 44 .962 1 .00 65 .99 8

ATOM 3034 N ASP B 175 20 .068 25 .058 44 .459 1 .00 64 .89 7

ATOM 3035 CA ASP B 175 19 .250 24 .895 43 .268 1 .00 66 .77 6

ATOM 3036 CB ASP B 175 17 .764 24 .785 43 .691 1 .00 68 .40 6

ATOM 3037 CG ASP B 175 16 .806 24 .566 42 .508 1 .00 70 .08 6

ATOM 3038 ODl ASP B 175 17 .038 23 .631 41 .695 1 .00 71 .56 8

ATOM 3039 OD2 ASP B 175 15 .809 25 .322 42 .404 1 .00 67 .36 8 ATOM 3040 C ASP B 175 19.480 26.067 42.298 1.00 67.13 6

ATOM 3041 O ASP B 175 19. 910 27. 160 42. 703 1. 00 67. 04 8

ATOM 3042 N VAL B 176 19. 214 25. 818 41. 018 1. 00 66. 07 7

ATOM 3043 CA VAL B 176 19. 364 26. 819 39. 981 1. 00 65. 28 6

ATOM 3044 CB VAL B 176 20. 616 26. 547 39. 112 1. 00 64. 59 6

ATOM 3045 CGI VAL B 176 20. 681 27. 529 37. 943 1. 00 62. 08 6

ATOM 3046 CG2 VAL B 176 21. 866 26. 645 39. 964 1. 00 64. 50 6

ATOM 3047 C VAL B 176 18. 139 26. 760 39. 088 1. 00 66. 92 6

ATOM 3048 O VAL B 176 17. 723 25. 682 38. 657 1. 00 68. 14 8

ATOM 3049 N THR B 177 17. 555 27. ,920 38. .816 1. 00 68. ,01 7

ATOM 3050 CA THR B 177 16. 393 27. ,988 37. ,939 1. 00 70. ,52 6

ATOM 3051 CB THR B 177 15. ,087 28. .139 38. .744 1. 00 69. ,59 6

ATOM 3052 OG1 THR B 177 15. ,203 29. .253 39. .638 1. ,00 70. ,12 8

ATOM 3053 CG2 THR B 177 14. ,821 26. .885 39. ,544 1. ,00 68. ,35 6

ATOM 3054 C THR B 177 16. 537 29. 173 36. ,984 1. 00 72. . 66 6

ATOM 3055 O THR B 177 17. 095 30. ,220 37. ,356 1. 00 74. 08 8

ATOM 3056 N GLN B 178 16. ,049 29. ,002 35. ,757 1. ,00 73. ,01 7

ATOM 3057 CA GLN B 178 16. ,121 30. ,057 34. .756 1. 00 74. ,26 6

ATOM 3058 CB GLN B 178 17. .006 29, ,619 33, .594 1. ,00 76. .29 6

ATOM 3059 CG GLN B 178 18. .090 28, ,628 33. .984 1. ,00 79, ,92 6

ATOM 3060 CD GLN B 178 19. ,227 28. ,575 32. .959 1. ,00 83. .13 6

ATOM 3061 OEl GLN B 178 18. .993 28 .495 31, .731 1. .00 83. .91 8

ATOM 3062 NE2 GLN B 178 20. ,469 28. .616 33, .458 1. .00 82. ,82 7

ATOM 3063 C GLN B 178 14. .725 30, .354 34, .232 1. .00 73, .95 6

ATOM 3064 O GLN B 178 14. .041 29, .454 33, .752 1. .00 75, .30 8

ATOM 3065 N LYS B 179 14. .306 31 .611 34. .310 1. ,00 73, .25 7

ATOM 3066 CA LYS B 179 12, .978 31 .995 33 .837 1. .00 72 .86 6

ATOM 3067 CB LYS B 179 12, .076 32 .307 35 .030 1, .00 75 .19 6

ATOM 3068 CG LYS B 179 12. .196 31 .282 36 .160 1, .00 78 .55 6

ATOM 3069 CD LYS B 179 11. .456 31 .735 37. .428 1. ,00 80 .12 6

ATOM 3070 CE LYS B 179 11, .845 30, .874 38. .631 1. .00 80, .51 6

ATOM 3071 NZ LYS B 179 13. .320 30, .987 38. .927 1. .00 81, .19 7

ATOM 3072 C LYS B 179 13. .101 33 .232 32 .961 1. .00 70 .68 6

ATOM 3073 O LYS B 179 13, .411 34 .311 33 .455 1, .00 70 .88 8

ATOM 3074 N LYS B 180 12, .852 33 .090 31 .665 1, .00 68 .28 7

ATOM 3075 CA LYS B 180 12 .970 34 .242 30 .776 1. .00 68 .69 6

ATOM 3076 CB LYS B 180 12 .873 33 .792 29 .305 1, .00 66 .36 6

ATOM 3077 CG LYS B 180 11 .517 33 .383 28 .831 1 .00 61 .57 6

ATOM 3078 CD LYS B 180 10 .763 34 .578 28 .296 1 .00 62 .84 6

ATOM 3079 CE LYS B 180 11 .419 35 .168 27 .058 1 .00 63 .27 6

ATOM 3080 NZ LYS B 180 11 .317 34 .295 25 .857 1 .00 64 .69 7

ATOM 3081 C LYS B 180 11 .914 35 .297 31 .096 1 .00 69 .36 6

ATOM 3082 O LYS B 180 11 .131 35 .112 32 .019 1 .00 70 .64 8

ATOM 3083 N ASN B 181 11 .922 36 .416 30 .366 1 .00 69 .86 7

ATOM 3084 CA ASN B 181 10 .927 37 .473 30 .560 1 .00 70 .42 6

ATOM 3085 CB ASN B 181 10 .755 37 .816 32 .052 1 .00 71 .53 6

ATOM 3086 CG ASN B 181 12 .058 38 .021 32 .760 1 .00 71 .03 6

ATOM 3087 ODl ASN B 181 12 .935 38 .731 32 .267 1 .00 71 .52 8

ATOM 3088 ND2 ASN B 181 12 .195- 37 .412 33 .940 1 .00 71 .36 7

ATOM_, 3089 C ASN B 181 11 .125 38 .768 29 .779 1 .00 70 .25 6

ATOM 3090 O ASN B 181 12 .104 39 .478 29 .975 1 .00 70 .25 8

ATOM 3091 N SER B 182 10 .162 39 .078 28 .911 1 .00 70 .77 7

ATOM 3092 CA SER B 182 10 .203 40 .297 28 .105 1 .00 70 .64 6

ATOM 3093 CB SER B 182 9 .107 40 .262 27 .045 1 .00 70 .47 6

ATOM 3094 OG SER B 182 9 .267 41 .327 26 .122 1 .00 71 .28 8

ATOM 3095 C SER B 182 9 .997 41 .500 29 .024 1 .00 70 .77 6

ATOM 3096 O SER B 182 9 .429 41 .359 30 .095 1 .00 72 .80 8

ATOM 3097 N VAL B 183 10 .442 42 .680 28 .600 1 .00 71 .20 7

ATOM 3098 CA VAL B 183 10 .334 43 .887 29 .425 1 .00 70 .43 6

ATOM 3099 CB VAL B 183 11 .337 43 .826 30 .630 1 .00 68 .47 6

ATOM 3100 CGI VAL B 183 12 .636 43 .178 30 .202 1 .00 68 .72 6 ATOM 3101 CG2 VAL B 183 11.625 45.230 31.148 1.00 67.78 6

ATOM 3102 C VAL B 183 10. 590 45. 189 28. 659 1. 00 70. 59 6

ATOM 3103 O VAL B 183 11. 522 45. ,282 27. 853 1. 00 71. 25 8

ATOM 3104 N THR B 184 9. 761 46. ,195 28. ,911 1. 00 70. 21 7

ATOM 3105 CA THR B 184 9. 949 47. ,480 28. 250 1. 00 71. 59 6

ATOM 3106 CB THR B 184 8. ,610 48. ,062 27. ,711 1. 00 70. ,78 6

ATOM 3107 OG1 THR B 184 8. 065 47. ,183 26. ,721 1. 00 69. ,37 8

ATOM 3108 CG2 THR B 184 8. ,836 49, .431 27. ,074 1. 00 69. ,81 6

ATOM 3109 C THR B 184 10. ,558 48. .447 29. ,271 1. ,00 73. ,13 6

ATOM 3110 O THR B 184 10. .240 48, ,384 30. .467 1. ,00 73. ,23 8

ATOM 3111 N TYR B 185 11. ,449 49, .319 28. .806 1. ,00 74, .37 7

ATOM 3112 CA TYR B 185 12. ,085 50. .287 29. .689 1. ,00 76. ,17 6

ATOM 3113 CB TYR B 185 13. ,614 50. .134 29. .663 1. , 00 77, ,19 6

ATOM 3114 CG TYR B 185 14. ,076 48, .723 29. .912 1. 00 78. ,36 6

ATOM 3115 CDl TYR B 185 13. ,942 47. ,745 28. ,928 1. 00 78. ,94 6

ATOM 3116 CEl TYR B 185 14. ,298 46. ,417 ^•29. ,178 1. 00 80. ,41 6

ATOM 3117 CD2 TYR B 185 14. .584 48. .344 31. ,154 1. ,00 79. ,09 6

ATOM 3118 CE2 TYR B 185 14. .944 47. .013 31. .413 1. 00 79. ,41 6

ATOM 3119 CZ TYR B 185 14. ,796 46. ,054 30. ,424 1. 00 79. ,27 6

ATOM 3120 OH TYR B 185 15. ,119 44, ,731 30. .677 1. ,00 79. ,15 8

ATOM 3121 C TYR B 185 11. .713 51, ,670 29. ,209 1. ,00 76. ,81 6

ATOM 3122 O TYR B 185 11, .669 51, .927 28, .003 1. .00 76. ,75 8

ATOM 3123 N SER B 186 11. .445 52, .563 30. .152 1. ,00 78. .68 7

ATOM 3124 CA SER B 186 11, .078 53, .941 29, .810 1, .00 80. ,00 6

ATOM 3125 CB SER B 186 11. .002 54, .795 31, .089 1. .00 80, .19 6

ATOM 3126 OG SER B 186 12, .160 54, .610 31. .902 1, ,00 79. ,86 8

ATOM 3127 C SER B 186 12 .100 54 .539 28, .832 1, .00 80, .21 6

ATOM 3128 O SER B 186 11 .745 55 .296 27, .923 1, .00 79, .15 8

ATOM 3129 N CYS B 187 13, .364 54 .171 29, .025 1. .00 80, .45 7

ATOM 3130 CA CYS B 187 14, .459 54, .653 28. .189 1. .00 80, ,85 6

ATOM 3131 C CYS B 187 1 .259 54 .260 26. .772 1. .00 81, .01 6

ATOM 3132 O CYS B 187 14, .510 55 .018 25, .838 1, .00 80, .34 8

ATOM 3133 CB CYS B 187 15. .787 53 .993 28, .574 1. ,00 81, .53 6

ATOM 3134 SG CYS B 187 15 .913 52 .165 28, .268 1, .00 84, .25 16

ATOM 3135 N CYS B 188 13 .791 53 .035 26, .637 1, .00 82, .80 7

ATOM 3136 CA CYS B 188 13 .712 52 .411 25 .339 1 .00 83 .26 6

ATOM 3137 C CYS B 188 12 .352 51 .851 24, .849 1, .00 82 .46 6

ATOM 3138 O CYS B 188 11 .733 50 .977 25 .491 1 .00 82 .70 8

ATOM 3139 CB CYS B 188 14 .811 51 .336 25 .365 1 .00 82 .41 6

ATOM 3140 SG CYS B 188 16 .353 51 .824 26 .282 1 .00 83, .49 16

ATOM 3141 N PRO B 189 11 .891 52 .346 23 .679 1 .00 81 .48 7

ATOM 3142 CD PRO B 189 12 .734 53 .291 22 .910 1 .00 81 .13 6

ATOM 3143 CA PRO B 189 10 .652 52 .037 22 .938 1 .00 79 .97 6

ATOM 3144 CB PRO B 189 10 .977 52 .510 21 .517 1 .00 80, .12 6

ATOM 3145 CG PRO B 189 11 .825 53 .725 21 .766 1 .00 80 .41 6

ATOM 3146 C PRO B 189 10 .133 50 .585 22 .941 1 .00 ^■78, .77 6

ATOM 3147 O PRO B 189 9 .063 50 .303 23 .490 1 .00 78 .66 8

ATOM 3148 N GLU B 190 10 .878 49 .671 22 .313 1 .00 77 .68 7

ATOM 3149 CA GLU B 190 10 .473 48 .254 22 .219 1 .00 73 .96 6

ATOM 3150 CB GLU B 190 11 .214 47 .570 21 .075 1 .00 75 .24 6

ATOM 3151 CG GLU B 190 11 .578 48 .475 19 .908 1 .00 77 .67 6

ATOM 3152 CD GLU B 190 10 .414 48 .680 18 .950 1 .00 79 .11 6

ATOM 3153 OEl GLU B 190 • 9 .731 47 .672 18 .617 1 .00 77 .05 8

ATOM 3154 OE2 GLU B 190 10 .200 49 .845 18 .526 1 .00 79 .84 8

ATOM 3155 C GLU B 190 10 .779 47 .482 23 .494 1 .00 71 .49 6

ATOM 3156 O GLU B 190 11 .317 48 .038 24 .460 1 .00 71 .14 8

ATOM 3157 N ALA B 191 10 .455 46 .191 23 .483 1 .00 68 .33 7

ATOM 3158 CA ALA B 191 10 .708 45 .331 24 .638 1 .00 66 .03 6

ATOM 3159 CB ALA B 191 9 .554 44 .340 24 .801 1 .00 65 .95 6

ATOM 3160 C ALA B 191 12 .035 44 .570 24 .489 1 .00 64 .66 6

ATOM 3161 O ALA B 191 12 .439 44 .225 23 .374 1 .00 63 .36 8 OJ en en 4^ 4^ 00 oo ro r o en σ en O en o en o en en ;_y ι_y to ' ;y ; ! ; ' ;_y ' fe ^, < ;_y

O O O O O O O O O O O O O O O O O O O Ω O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O Q O Q g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g

L L w ω ω sj Lo J LJ o ω t IO tO IO M - t tO - lO tO M P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P to c t μ-> o o o o o o o so LD So so vo so so ιo ιo co oo oo oo ) oo oD Co oD θD -j --J -j t>o μ-' o ω co - ι Lπ j-. M μ^j o o ∞ -o. n Lπ _p> ω

Ω Ω lg O Ω O Ω Ω O Ω Ω Ω Ω Ω !zj O Ω O O Ω Ω Ω Ω ≥I Ω Ω Ω Ω Ω ^ O Ω O O Ω Ω Ω -Zj O Ω O O Ω Ω Ω Ω IZj O Ω O Ω Ω Ω Ω Ω Ω Ω Ω ≥l ω Ω ω Ω Ω W M M t) Ω ω Ω Ω td * α O Ω M B M O Q ω > S N H ϋ H tl O tI) | to μ-> to μ-¹ to μ t) μ ts μ-¹ tsj to μ^ (-> tr¹ tr¹ tr¹ (n in ui to M m < < < < ha < hy <ot Ω Ω Ω Ω Ω Ω < < < < '

B IS H H ^{" ■} M ^{" ■} H M K K ft Ω |→ Ω¹ Ω f tr¹ tr¹ f IT¹ IT¹ )* )J Dl α G v p d p pd p f t f t ^lti ω ω w ω ω ω dd ω ω ω ω ω ω ω ω ω ω ω .jd ω ω ω ω μ^j H μ-> μ^j μ^j μ^j μ-> μ^j μ^j μ-' R ^j μ^j μ-> μ^j μ-^ι μ^j μ^j μ-^l μ^j μ^j μ^j μ^j μ^j μ-^ι μ^j μ-> μ-^ι μ^j μ^j μ^j μ-' μ^j μ^j -' H

> ) o l ) l ) LD LD _> _> l^ O ) SO s ) O s£) D so o o v_D O so so o o sθ so D θ so co ∞ oo co co co -o l -o -o ι ι --J cn __n -_n σ> __n OT __n _Λ __n Lπ Lπ Lπ Lπ Lπ

to t t p p p p p p p p u -O t p p p p p p μ p p p p p p p p p μ-' μ-^» μ-^> μ-^l μ-^ι μ-^ι μ-^ι μ-' μ-^ι μ-> μ^j μ-> μ-^s μ-^s μ-> μ-> μ-' μ-> μ-^l μ-' μ-' μ-^ι μ^j μ-^> μ^Λ μ-' μ-> μ-^λ μ-^ι μ-> i) p o i£Ho n ι ∞ α) VD ω o o o ctκιι m ^ι ^ ^ *O\ uι σι σι m -J ι ! ~J Λ rf^ πui Lπ πcn Lπ oΛ Lπ H - ω ω ω ι ) _rι σι σι σι uι l- Ui σι ω to

O Lπ Lπ ^j OT o ιχι μ-^ι i_o OT o so o ω u w ω ω LJ ω ω ω w ω tAj ω ω ijj ω w ijj ω w w ω ω ω ω ω ω ω J w ω ω ω ω ι^ ω ω ω ω ιf. ω ω ω ω ω ι_j ω ιii ιi-. ^ ιj!. ι|i _a ι|i ||_> ι|i ιFs ιti. ι)i ιi-. p o p o lJ M - _ ^- u t p to ι ιl- ω ιl- σl Co -o m ol Ul Ol σl Ul ω ^) ^ ι_^ (!l m ] o uj io o co o io - i m -J ω ra iD μ t t tD ^ σi ui xi oi W ili ω Λi ι(^ ιo co p u (_!. U (- - o P - P μ *_-> cωo oo __vj μp uuιι μμ pp uuιι pp uuιι two oo uuιι σσιι <cDfl oo pμ ω ω ιi_D] p iιoo ωco raco uuiι wω i! θo u uιi ccoo i(^2, oσiι cαoi ^j moo μp uω ω) i^ii ^ιp. tt) ωω ^j ]j L^n ιi- uι ) ω σi Ui co co o o - Ui iπ o to o o ui ∞ co ω io ω u ω oi t σi o io u io ui io iD Ui -J ui σi o oi iii ^ p u LLππi ωcω_o c__Do ϋϋoo ϋϋJJ ιι((ii.. LLππ ccnn ιιff==.. θθ LLoo ccoo --JJ ttoo LLππ LLoo cn ~j σ

-j ω i co ui si co p co --^j n ui ips. ι^> urⁱ-o p ^i p ui αi tΛ μ ω is^j μ ϋi ω io ui m ' i ui iti ω o αi to iD t oj n σi μ i to m iD t μ o ili Lπ oo ifi Co co i^ cn

^ i^ il^ ^ ifi ^ tl^ ij^ ω w ω ϋJ LJ ω ω ω ω ω ω ω io j ω ω μ-^, _-> μ-¹ o o o o o Qo oo -j ^ -_n Lπ cn Lπ Lπ Lπ co . -j cn Lπ .ι^ Lϋ t>o tNJ oo μ-^» o o o m ^o w uι m U ^ o σl _ α) M ^ l u l M ⁾ Ol O ϋl ra lJ m _ ^ t ιB t ι co o p l U) o o ι ^D P Ol o ιΛ t ^ m ω ω ^ m ^ p o o o o o o o ul 01 w o -> o Lπ to o --j ω _θ c_ o Lπ L w vr. Lπ Lθ ∞ σι μ^Λ i_o M c θ --^ c ∞ bo >i-> o Ln o ω -> μ-> σ^ i£> __^ --^ --o ∞ tθ tθ μ-^{ι μ}-^λ ω ^ μ-> -j co oo Ln o o c_^

H P H H P H P P P P P ρ^j P^Λ μ-^ι μⁱ μ-^l l-^ι l^j μ-> μ-^l μ-> μ-^l μ-» μ-> μ-' μ-> μ-¹ _-> μ-¹ μ-¹ μ-^ι μ-> μ^j (-^l _-' -' μ-^l μ-ⁱ μ-^ι -^ι μ-^ι μ-' _-' μ-> μ-^ι μ-> μ-> o o o o σ o o o o o o σ o o o o o o σ o o o o o o σ σ o o o o o o σ o o o o σ o o o o o o σ o o o o o o σ o o o o o o o o o o o o o o o o o o o o o o o σ o o o c O o o o o o o o o o o o o o o o o o σ o o o o o σ o o o o o o σ o o o o

Lπ Lπ oo ∞

-o c» c o σι cn ι cΛ cn co cΛ c_ ι oo cn σι cn σ^ <_n ) cxι cn c_o oo cn o cn c ι -j ∞

ATOM 3223 CG LEU B 199 24.108 30.,670 42..358 1.00 59.80 6

ATOM 3224 CDl LEU B 199 24. 135 29. ,209 41. .927 1. ,00 60. 58 6

ATOM 3225 CD2 LEU B 199 25. ,446 31. .304 42. .063 1. 00 60. 42 6

ATOM 3226 C LEU B 199 21. ,369 30, .885 43, .395 1. ,00 60. ,51 6

ATOM 3227 O LEU B 199 21. ,759 31, .788 44, .136 1. .00 61. .67 8

ATOM 3228 N . ASN B 200 20. .754 29, .801 43, .838 1. ,00 60. ,15 7

ATOM 3229 CA ASN B 200 20. .539 29, .607 45, .252 1. .00 57. .57 6

ATOM 3230 CB ASN B 200 19. .188 28, .919 45, .499 1. .00 60. .95 6

ATOM 3231 CG ASN B 200 18. .936 28 .642 46, .968 1. .00 62. .80 6

ATOM 3232 ODl ASN B 200 19. .167 29 .504 47, .820 1. ,00 65. ,10 8

ATOM 3233 ND2 ASN B 200 18. .465 27, .443 47, .275 1. ,00 59. ,90 7

ATOM 3234 C ASN B 200 21. .691 28, .736 45. .712 1. ,00 55. ,80 6

ATOM 3235 O ASN B 200 21. .793 27 .569 45, .325 1. .00 56. .54 8

ATOM 3236 N PHE B 201 22. .561 29, .316 46, .527 1. .00 53. ,98 7

ATOM 3237 CA PHE B 201 23. .725 28 .615 47 .042 1. ,00 53. .98 6

ATOM 3238 CB PHE B 201 24, .960 28, .975 46, .226 1. ,00 53. ,35 6

ATOM 3239 CG PHE B 201 25, .418 30 .404 46 .418 1, .00 51. .26 6

ATOM 3240 CDl PHE B 201 26. ,633 30 .690 47 .050 1. .00 50. .15 6

ATOM 3241 CD2 PHE B 201 24. .615 31 .472 46 .000 1, .00 50. .67 6

ATOM 3242 CEl PHE B 201 27. .038 32 .015 47 .264 1, .00 45, ,58 6

ATOM 3243 CE2 PHE B 201 25. ,016 32, .799 46 .213 1, .00 47. .69 6

ATOM 3244 CZ PHE B 201 26. .227 33, .062 46 .845 1. .00 46. .26 6

ATOM 3245 C PHE B 201 23. .943 29, .080 48 .456 1. ,00 55. .95 6

ATOM 3246 O PHE B 201 23, .275 30 .017 48 .912 1, .00 56. .39 8

ATOM 3247 N ARG B 202 24. .896 28 .443 49 .132 1. .00 56. .81 7

ATOM 3248 CA ARG B 202 25, .223 28, .793 50 .506 1, ,00 60. .77 6

ATOM 3249 CB ARG B 202 24, .255 28 .104 51 .460 1. .00 64, .25 6

ATOM 3250 CG ARG B 202 24, .491 26 .625 51 .497 1. .00 66, .78 6

ATOM 3251 CD ARG B 202 23, .494 25 .893 52 .344 1, .00 70, .08 6

ATOM 3252 NE ARG B 202 23, .768 24 .454 52 .333 1, .00 72, .69 7

ATOM 3253 CZ ARG B 202 22 .945 23 .528 52 .825 1, .00 73, .67 6

ATOM 3254 NHl ARG B 202 21, .781 23 .884 53, .375 1. .00 74, .01 7

ATOM 3255 NH2 ARG B 202 23. .281 22, .245 52, .760 1. .00 73. .29 7

ATOM 3256 C ARG B 202 26, .635 28 .328 50 .843 1. .00 61, .67 6

ATOM 3257 O ARG B 202 27. ,181 27, .450 50, .183 1. ,00 62. .10 8

ATOM 3258 N LYS B 203 27 .225 28 .918 51 .875 1. .00 62, .58 7

ATOM 3259 CA LYS B 203 28. .549 28 .505 52 .298 1. .00 62. ,87 6

ATOM 3260 CB LYS B 203 29 .067 29 .417 53 .399 1. .00 62. .83 6

ATOM 3261 CG LYS B 203 30, .400 28 .995 53 .967 1. .00 62, .29 6

ATOM 3262 CD LYS B 203 30, .765 29 .871 55 .141 1, .00 65, .39 6

ATOM 3263 CE LYS B 203 32, .135 29 .519 55 .689 1, .00 67, .38 6

ATOM 3264 NZ LYS B 203 33. .232 29, .772 54, .695 1. ,00 70, .43 7

ATOM 3265 C LYS B 203 28, .387 27 .101 52 .854 1, .00 64, .30 6

ATOM 3266 O LYS B 203 27, .318 26 .736 53, .371 1. ,00 65, .43 8

ATOM 3267 N , LYS B 204 29 .446 26 .312 52 .745 1, .00 66, .12 7

ATOM 3268 CA LYS B 204 29, .417 24 .955 53 .246 1, .00 67, .10 6

ATOM 3269 CB LYS B 204 30, .701 24 .223 52 .860 1, ,00 63, .37 6

ATOM 3270 CG LYS B 204 30, .745 23 .853 51 .379 1, ,00 60, .21 6

ATOM 3271 CD LYS B 204 31, .940 22 .966 51 .055 1, .00 58, .61 6

ATOM 3272 CE LYS B 204 31, .955 22 .553 49 .582 1, .00 57 .79 6

ATOM 3273 NZ LYS B 204 33 .202 21 .808 49 .238 1, .00 53 .82 7

ATOM 3274 C LYS B 204 29 .293 25 .081 54 .745 1, .00 70 .90 6

ATOM 3275 0 LYS B 204 29, .893 25 .989 55 .339 1, ,00 72, .60 8

ATOM 3276 N GLY B 205 28, .489 24, .192 55, .342 1. ,00 74. ,01 7

ATOM 3277 CA GLY B 205 28 .260 24 .197 56 .783 1, .00 74, .37 6

ATOM 3278 C GLY B 205 29, ,305 23, .430 57, .576 1. .00 75. ,59 6

ATOM 3279 OTl GLY B 205 30 .276 22 -932 56 .958 1, .00 75 .56 8

ATOM 3280 OT2 GLY B 205 29, .163 23 .331 58 .822 1. .00 76, .47 8

ATOM 3281 CB PHE C 1 16 .639 48 .183 2 .177 1 .00 71 .30 6

ATOM 3282 CG PHE C 1 17 .365 49 .162 1 .297 1, .00 73, .66 6

ATOM 3283 CDl PHE C 1 18 .546 48 .805 0. .647 1. .00 74, .99 6 ATOM 3284 CD2 PHE C 1 16.,889 50..471 1.,160 1.,00 75..46 6

ATOM 3285 CEl PHE C 1 19. ,257 49. ,743 -0. .138 1. ,00 77. .68 6

ATOM 3286 CE2 PHE C 1 17, .590 51, .421 0. .380 1. ,00 76, .94 6

ATOM 3287 CZ PHE C 1 18. ,779 51. ,054 -0. ,271 1. 00 77. ,37 6

ATOM 3288 C PHE C 1 16. ,469 45. ,841 2. .896 1. ,00 69. .30 6

ATOM 3289 O PHE C 1 15. .487 45, .976 3, .637 1, ,00 68, .12 8

ATOM 3290 N PHE C 1 15, ,624 46. .515 0, .608 1. ,00 67. .59 7

ATOM 3291 CA PHE C 1 16. .651 46. ,733 1, .669 1. ,00 69. ,36 6

ATOM 3292 N ASP C 2 17, ,421 44, .940 3, .123 1. ,00 69. .61 7

ATOM 3293 CA ASP C 2 17, ,373 44, .071 4, .298 1. .00 68, .32 6

ATOM 3294 CB ASP C 2 17. ,364 42. ,592 3, ,882 1. ,00 69, .98 6

ATOM 3295 CG ASP C 2 18. .729 42. ,092 3, ,426 1. ,00 71, ,56 6

ATOM 3296 ODl ASP C 2 19. .586 41, .867 4. .316 1. ,00 71, ,73 8

ATOM 3297 OD2 ASP C 2 18. ,936 41. ,926 2, ,187 1. ,00 72. ,36 8

ATOM 3298 C ASP C 2 18. ,615 44, .399 5, .116 1. ,00 66, .00 6

ATOM 3299 O ASP C 2 19, .617 44. .865 4. .562 1. ,00 67, .56 8

ATOM 3300 N ARG C 3 18, .550 44, .165 6, .423 1, .00 62, .29 7

ATOM 3301 CA ARG C 3 19, .663 44, .455 7 .320 1, ,00 59. .37 6

ATOM 3302 CB ARG c 3 19, ,515 43. .661 8, .604 1. ,00 56, ,89 6

ATOM 3303 CG ARG c 3 18, .280 44. .017 9, .387 1. .00 55, .35 6

ATOM 3304 CD ARG c 3 18, .177 43, .172 10, .640 1. ,00 57, .70 6

ATOM 3305 NE ARG c 3 16, .947 43, .437 11. .378 1. ,00 60, .36 7

ATOM 3306 CZ ARG c 3 16, .714 44, .540 12, .084 1. .00 62, .92 6

ATOM 3307 NHl ARG c 3 17 .623 45 .503 12 .166 1, .00 62 .53 7

ATOM 3308 NH2 ARG c 3 15 .554 44 .689 12 .700 1, .00 64 .87 7

ATOM 3309 C ARG c 3 21, .060 44. .236 6, .749 1. ,00 59. ,30 6

ATOM 3310 O ARG c 3 21, .970 45, .008 7, .051 1, .00 61, .36 8

ATOM 3311 N ALA c 4 21, .257 43, .215 5 .920 1, .00 57, .54 7

ATOM 3312 CA ALA c 4 22, .595 43. .023 5, .379 1. ,00 55, .37 6

ATOM 3313 CB ALA c 4 22. ,686 41, .727 4, .610 1. ,00 53, .55 6

ATOM 3314 C ALA c 4 22 .947 44 .186 4 .478 1, .00 5 .97 6

ATOM 3315 O ALA c 4 24, .020 44, .764 4, .603 1. .00 55, .12 8

ATOM 3316 N ASP c 5 22, .034 44, .534 3, .575 1. ,00 56, .24 7

ATOM 3317 CA ASP c 5 22 .265 45, .632 2 .646 1, ,00 56 .25 6

ATOM 3318 CB ASP c 5 21, .081 45, .795 1, .680 1. .00 58, .72 6

ATOM 3319 CG ASP c 5 20, .773 44 .529 0 .906 1, .00 62 .35 6

ATOM 3320 ODl ASP c 5 21, .715 43, .900 0, .364 1, .00 63, .21 8

ATOM 3321 OD2 ASP c 5 19, .574 44, .171 0, .834 1. .00 65, .38 8

ATOM 3322 C ASP c 5 22, .471 46, .935 3, .406 1, ,00 55, .27 6

ATOM 3323 O ASP c 5 23, .294 47, .764 3, .020 1. ,00 54, .31 8

ATOM 3324 N ILE c 6 21, .732 47, .110 4, .495 1, ,00 53, .55 7

ATOM 3325 CA ILE c 6 21, .840 48, .339 5, .270 1. .00 54, .16 6

ATOM 3326 CB ILE c 6 20 .713 48 .456 6 .311 1 .00 54 .45 6

ATOM 3327 CG2 ILE c 6 20: .811 49. .793 7. .021 1. ,00 52, ,65 6

ATOM 3328 CGI ILE c 6 19 .352 48, .344 5 .612 1, .00 56, .53 6

ATOM 3329 CDl ILE c 6 18 .146 48 .530 6, .524 1, .00 56 .74 6

ATOM 3330 C ILE c 6 23, .178 48, .475 5. .972 1. ,00 52. ,95 6

ATOM 3331 O ILE c 6 23, .872 49, .487 5 .818 1. .00 53, .74 8

ATOM 3332 N LEU c 7 23, .543 47, .455 6, .741 1, .00 51 .30 7

ATOM 3333 CA LEU c 7 24, .814 47, .462 7, .460 1. .00 49, .62 6

ATOM 3334 CB LEU c 7 24 .931 46, .194 8, .293 1. .00 47, .45 6

ATOM 3335 CG LEU c 7 23, .912 46 .136 9 .429 1. .00 47, .62 6

ATOM 3336 CDl LEU c 7 .23, .819 44, .743 10, .014 1. .00 48, .73 6

ATOM 3337 CD2 LEU c 7 24, .321 47, .122 10, .486 1. .00 47, .41 6

ATOM 3338 C LEU c 7 25, .970 47, .559 6, .465 1, .00 49, .71 6

ATOM 3339 O LEU c 7 26, .951 48. .269 6. ,677 1. ,00 47, .57 8

ATOM 3340 N TYR c 8 25 .827 46, .845 5 .361 1. .00 52 .00 7

ATOM 3341 CA TYR c 8 26 .830 46 .838 4 .318_. 1, .00 53 .34 6

ATOM 3342 CB TYR c 8 26 .367 45, .961 3, .167 1. ,00 53, .82 6

ATOM 3343 CG TYR c 8 27 .335 45, .969 2, .020 1. .00 57, .66 6

ATOM 3344 CDl TYR c 8 28 .552 45, .289 2, .106 1. .00 58, .72 6 eτ> en en 4^ ω ω IV) o en o en o en o en o en en ;__s ;_y to ;w ' to ' ;y ; ;»

►β t^ !-3 !-3 ι-3 --3 ι-3 β >-3 >-3 ^ >^ ^!-3 ι^ β ι-3 >-3 β ^ β e β β ^!-a B !-3 β e β β β H ι-3 β ι-3 ^ >-3 β β ι- β

OO O OO O O O OO O O O OO O O O O O OO O OOOO O OO O O O O O OOO O O O O O O O O OQ O O O Q O Q Q Q Q O O O g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g gg g g g g g g g g g g g g g g g g g g g g

O o i ω J ω ω ω ω O Lj ω ω ϋJ o ω Lo L Lj ω LO J ω

^ ^ ^ ^ ^ if^ ω o ω o ϋj ω ω ω ω ω ω ω j ω L ω L Lo o i ω

^ o ^ o ^ o ^ o ^ σ 2 yo ^yo yo o ^yo o o o o o <x> co tt) <x> o co tx> a co B i ^ i i ^ ui Λ^ ω ω p o ^o ffl ^ (n _n _l ω ^) P o ^o co ^ (Il W _- U - p o ω t_) l ol lΛ ft w M p o ω (D ^ m u ^ ι<J - P o ιo co ^ m ul (- u ^) p o ^D α) J ol

Ω Ω O Ω ≥| Ω O Ω Ω l2j O Ω Ω O Ω Ω !2| 0 Ω _30 Ω Ω Ω Ω ≥; 0 Ω g Ω S Ω Ω Ω Ω ≥l O Ω Ω Ω Ω Ω Ω ^O Ω _z!O Ω ΩΩ 30 Ω OΩ ΩΩ α Ω ω Ω ω ; Ω Ώ H M O Ω ω > ffi N M O Q SI ^ α Ω Ω ω if o α Ω ω m ii B U co μ-> ω _> μ-> μ-> co to p to to

^ l l» ^ m t(i to ω [n to ιa ι3 i-3 ι-3 i-3 β β Ω Ω Ω Ω Ω Ω Ω Ω Ω >^< >' < ' _S' >^I < H H H H H H H ^ ' ' ' ' ' l-3 ι-3 β ι-3 β pd pd pd pd pd M M H H W W K ffi t t t ¹. p ¹ p p p d pd pd pd pd pd pd pd Pd pd t^{1 <} f t¹ F t¹ P tti ω w ffi ω tn Ki ffl i κ_ K! | n n n O O ^ ^ » » » » ^ W 3 W ^ S ^ a ? S ? a ? ^ a a Q Q n fl Q O O Q O O O I?l B B B B H B g S -3 g -! 3 ? 2! ?i _!) ?l ?i ftl p⁾ Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω O Ω Ω Ω O Ω Ω Ω Ω Ω Ω Ω O Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω ^{j j} μ-^> μ^j π Lπ π π π

ω ω ^ ω ω ω ω Lo ω ω o LJ L io co tsO o w ω ω ω ω ω π #» .t-> __^ ω ω _sj o o μ-' o μ^j o o oD <£> o o c μ-^ι ω ^j to μ^j o μ-^λ o _- μ^j ) W μ-> ω o ι ^ π ι_^ Lπ o ι ω u_ι o t Lu cn π ^ π o t --J ι ω m H o cn --J - . cx) μ-> ∞ oo c L ι> t . ^ Lπ io μ-¹ ι^ _^ Lπ o ω oo [o o c_o -^l i -> oo -J R i£> o ∞ d-__^, oo j |i-. π co ^j c ω ω ^ -j ^ ω ω w μ-> o .!i Ln .l^ π Lυ Lπ uι --J ι co

Lπ Lπ Lπ Lπ π π π Ln π Lπ t_π Lπ Lπ Lπ π π π Lπ π Lπ ^ ^ rf^ ι)^ Lπ Lπ Lπ Ln π ιi-» ₁^ ^ ιi^ ι_o co c_o -o c_n π Lπ Lπ ^ Ln ι^ c Lπ ι{^ .(-> ^ .i-» Lo t -θ --o _ co so o o o o J io cπ ω i o ^i ^ c -l^ ^ j^ Lo Lo cn so iJ^ o -vj tNJ co to μj _ht^ j -j ω oo ω iJ σi oi m iO i ω p w o iD P i - co io M ^ ^ ra o i- oi ra ω oi ω ω m ω oi ω w o w ω ω u oi ui ui ui ^ J U vi W i o m μ^j σ. -^j ω ∞ ω Lπ t>o -^{l (}_jι bθ σ ι)__» t Ln -sJ ιf--. θD ∞ c_n D μ-^s ∞ ι_o H

(- iji j αi sj m io iB w ^ ^ ^ p u io u u M M μ μ μ o μ w ^ ui ij αi ^ i iB Oi m m oi m iJi cΛ tB vi o vi cii ui w ^ p o μ - i w ω tii o o o μ ω -J to μ^j ∞ π o ^ o ∞ cΛ ^J i^ ω π i M i^ W ∞ ∞ -O π ω oo o NJ -J i^ c >l-» ιl^ t> -' _ _ θ Lπ cn t (_n _π -j Lπ Ln μ-> [o o --J J o Lo - . t\3 i£> Lπ ^ oo oo ι ι rι ! ιi-. ι c Lπ ι ^ o ι ω L Lo oo tθ ιi^ ^ t c_ Lo θ Lπ oo o μ-' σ -o ω

Pⁱμ^jt^ Hμⁱμ^lι^ ^Λμ-^ι μ^j ι-^j _-^ιμ^Λμ-^ι μ-' i^j μ-¹ ^ μ-ⁱ H H μ^j μ-^ι μ-' μ-^ι μ-^ι μ-^» μ-^ι -^ι -' μ^j μ-> μ-*μ-^ι μ-^ι μ-> h-^l ι-^j h-> μ-» μμppppppμpμμ ι-> μ-> μ-> ooσoo ooooo oooooooo oooooooooooo oooσoooooσooooo oooσo oo oooσoooo ooooo ooooo o o o oσo oσσoooooσooooooo oooooooo oo ooooo oooooσoooo σ^ --j -J o c_n cn c^ σ -J oo σ^ ∞ c c_ ! θo c_ o ∞ c_n c _ oo m ι ∞ _ c c^

ATOM 3406 NE ARG C 15 36.475 59.479 5.475 1.00 64.09 7

ATOM 3407 CZ ARG C 15 37. 287 60. ,488 5. 180 1. 00 63. ,60 6

ATOM 3408 NHl ARG c 15 36. 873 61. 450 4. 375 1. 00 62. 16 7

ATOM 3409 NH2 ARG c 15 38. ,516 60, ,526 5. ,688 1. ,00 66. ,26 7

ATOM 3410 C ARG c 15 34. 081 57. ,753 9. 598 1. 00 54. ,80 6

ATOM 3411 O ARG c 15 33. .736 58, ,874 9, .969 1. ,00 54. ,31 8

ATOM 3412 N PRO c 16 34. 483 56. ,811 10. 460 1. 00 53. ,16 7

ATOM 3413 CD PRO c 16 34. 921 55. ,451 10. .106 1. 00 49. ,32 6

ATOM 3414 CA PRO c 16 34. 547 57, ,012 11. ,911 1. ,00 51. ,93 6

ATOM 3415 CB PRO c 16 35. 072 55. ,668 12. 429 1. 00 49. 26 6

ATOM 3416 CG PRO c 16 34. ,647 54, .702 11. ,387 1. ,00 48. .93 6

ATOM 3417 C PRO c 16 35. .420 58, ,172 12. 356 1. 00 51. ,62 6

ATOM 3418 O PRO c 16 35. .266 58, ,663 13. .468 1. ,00 52. ,27 8

ATOM 3419 N ASP c 17 36. .337 58, .608 11. .501 1. .00 51, .78 7

ATOM 3420 CA ASP c 17 37. ,219 59. .706 11. .863 1. ,00 54. .16 6

ATOM 3421 CB ASP c 17 38. ,597 59. .526 11. .209 1. .00 59. .36 6

ATOM 3422 CG ASP c 17 39. ,421 58. ,411 11. ,859 1. ,00 64, ,02 6

ATOM 3423 ODl ASP c 17 39. ,200 58. ,134 13. ,067 1. ,00 64. ,61 8

ATOM 3424 OD2 ASP c 17 40. .299 57, .824 11. .170 1. .00 64. ,76 8

ATOM 3425 C ASP c 17 36. .680 61, .080 11. .499 1. ,00 53. .77 6

ATOM 3426 O ASP c 17 37. .350 62, .088 11. .736 1. .00 54, .82 8

ATOM 3427 N VAL c 18 35. .473 61, .129 10. .944 1. .00 53, .02 7

ATOM 3428 CA VAL c 18 34. .902 62 .398 10, .528 1. ,00 53, .40 6

ATOM 3429 CB VAL c 18 34. . 699 62. ,421 9. .003 1. ,00 53, .89 6

ATOM 3430 CGI VAL c 18 34, .194 63, .785 8, .563 1. .00 53, .62 6

ATOM 3431 CG2 VAL c 18 36. ,013 62, .087 8. ,308 1, ,00 52. .31 6

ATOM 3432 C VAL c 18 33. ,589 62, .771 11. .201 1. ,00 54, .75 6

ATOM 3433 O VAL c 18 32, .573 62 .097 11, ,046 1. .00 54, .30 8

ATOM 3434 N ILE c 19 33, .634 63, .870 11, .944 1, .00 56, .30 7

ATOM 3435 CA ILE c 19 32, .480 64 .401 12, .662 1, ,00 55, .34 6

ATOM 3436 CB ILE c 19 32^', .934 65 .631 13, .519 1, .00 54, .46 6

ATOM 3437 CG2 ILE c 19 33, .362 66, .777 12. .618 1. .00 53, .28 6

ATOM 3438 CGI ILE c 19 31, .827 66 .078 14, ,467 1. .00 53, .52 6

ATOM 3439 CDl ILE c 19 32, .318 67 .022 15, .525 1, .00 50 .20 6

ATOM 3440 C ILE c 19 31 .392 64 .784 11, .644 1, .00 56 .25 6

ATOM 3441 O ILE c 19 31 .675 65 .474 10, .653 1, .00 56 .64 8

ATOM 3442 N PRO c 20 30. .142 64, .318 11, .861 1, ,00 55, .95 7

ATOM 3443 CD PRO c 20 29 .756 63 .451 12, .978 1, .00 55, .72 6

ATOM 3444 CA PRO c 20 28 .980 64 .574 10, .996 1 .00 57 .07 6

ATOM 3445 CB PRO c 20 27 .912 63 .627 11 .540 1 .00 55 .92 6

ATOM 3446 CG PRO c 20 28 .673 62 .639 12, .349 1, .00 57, .30 6

ATOM 3447 C PRO c 20 28 .500 66 .023 11, .035 1, .00 59 .85 6

ATOM 3448 O PRO c 20 27 .326 66 .290 11 .270 1, .00 58 .63 8

ATOM 3449 N THR c 21 29 .416 66 .947 10, .782 1, .00 64 .15 7

ATOM 3450 CA THR c 21 29 .123 68 .370 10. .797 1, .00 68, .52 6

ATOM 3451 CB THR c 21 30 .421 69 .169 11, .046 1, .00 68, .47 6

ATOM 3452 OG1 THR c 21 30 .496 69 .477 12, .440 1 .00 70 .47 8

ATOM 3453 CG2 THR c 21 30 .470 70 .455 10, .216 1 .00 69 .90 6

ATOM 3454 C THR c 21 28 .424 68 .913 9, .555 1, .00 72, .31 6

ATOM 3455 O THR c 21 28 .826 68 .631 8, .412 1, .00 71, .25 8

ATOM 3456 N GLN c 22 27 .384 69 .709 9 .805 1 .00 76 .61 7

ATOM 3457 CA GLN c 22 26 .599 70 .346 8 .747 1 .00 80 .67 6

ATOM 3458 CB GLN c 22 25 .112 70 .087 8 .972 1 .00 81 .49 6

ATOM 3459 CG GLN c 22 24 .749 68 .606 9 .029 1 .00 82 .93 6

ATOM 3460 CD GLN c 22 23 .534 68 .351 9 .900 1 .00 83 .25 6

ATOM 3461 OEl GLN c 22 23 .566 68 .595 11 .120 1 .00 84 .14 8

ATOM 3462 NE2 GLN c 22 22 .452 67 .867 9 .285 1 .00 83 .14 7

ATOM 3463 C GLN c 22 26 .865 71 .846 8 .814 1 .00 83 .04 6

ATOM 3464 0 GLN c 22 26 .382 72 .523 9 .730 1 .00 83 .36 8

ATOM 3465 N ARG c 23 27 .635 72 .357 7 .849 1 .00 85 .46 7

ATOM 3466 CA ARG c 23 27 .985 73 .783 7 .802 1 .00 86 .39 6 ATOM 3467 CB ARG C 23 26..722 74..654 7,,771 1..00 87.,20 6

ATOM 3468 CG ARG C 23 26, .050 74. .710 6, .393 1. ,00 89. .96 6

ATOM 3469 CD ARG C 23 24. ,797 73. ,834 6. ,297 1. ,00 90. ,96 6

ATOM 3470 NE ARG C 23 24, .282 73. ,771 4, .920 1. .00 93. .30 7

ATOM 3471 CZ ARG C 23 23. .996 74. ,830 4, .145 1. .00 ^'94. .77 6

ATOM 3472 NHl ARG C 23 24, .167 76. ,083 4, ,591 1. . 00 94. .25 7

ATOM 3473 NH2 ARG c 23 23. .537 74. ,640 2. ,905 1. .00 94. ,32 7

ATOM 3474 C ARG c 23 28, .828 74. ,134 9, .013 1. ,00 85. ,61 6

ATOM 3475 O ARG c 23 29, .599 73. .302 9, .495 1. .00 85. .98 8

ATOM 3476 N ASP c 24 28. .700 75. .358 9, .503 1. ,00 85. ,83 7

ATOM 3477 CA ASP c 24 29, .462 75. ,755 10, .685 1. ,00 86. . 66 6

ATOM 3478 CB ASP c 24 29, .625 77, .283 10, .785 1. .00 90. .61 6

ATOM 3479 CG ASP c 24 29 .385 78, .002 9 .458 1. .00 92, .74 6

ATOM 3480 ODl ASP c 24 30, .108 77. .704 8. .471 1. ,00 93. .41 8

ATOM 3481 OD2 ASP c 24 28, .468 78. .868 9, .418 1, .00 93. .68 8

ATOM 3482 C ASP c 24 28, .679 75, .280 11 .907 1, .00 85, .20 6

ATOM 3483 0 ASP c 24 29. ,053 75. .591 13. .052 1, ,00 85. ,29 8

ATOM 3484 N ARG c 25 27, .587 74, .553 11 .660 1. .00 82, .29 7

ATOM 3485 CA ARG c 25 26. ,761 74. .039 12. .742 1. .00 79. .75 6

ATOM 3486 CB ARG c 25 25 .422 73, .522 12 .210 1. .00 82, .55 6

ATOM 3487 CG ARG c 25 24. .428 74. .588 11, .781 1. .00 86, .91 6

ATOM 3488 CD ARG c 25 23 .026 73, .964 11 .594 1. .00 91, .01 6

ATOM 3489 NE ARG c 25 22 .007 74, .963 11 .252 1 .00 94, .97 7

ATOM 3490 CZ ARG c 25 20, ,702 74, .705 11, .146 1. .00 96 . .54 6

ATOM 3491 NHl ARG c 25 20, .253 73, .471 11 .356 1, .00 91 , .65 7

ATOM 3492 NH2 ARG c 25 19, .844 75, .679 10, .837 1. . 00 96 . .40 7

ATOM 3493 C ARG c 25 27 .456 72 .906 13 .490 1 .00 76 .53 6

ATOM 3494 O ARG c 25 28, .004 71. .987 12, .876 1. ,00 78. .25 8

ATOM 3495 N PRO c 26 27 .449 72, .963 14 .829 1 .00 72, .39 7

ATOM 3496 CD PRO c 26 27 .074 74, .126 15 .647 1, .00 71, .70 6

ATOM 3497 CA PRO c 26 28, .073 71, .935 15, .660 1. ,00 68. .13 6

ATOM 3498 CB PRO c 26 28 .087 72 .574 17 .050 1 .00 69, .12 6

ATOM 3499 CG PRO c 26 28, .066 74, ,039 16 .770 1, .00 69, .98 6

ATOM 3500 C PRO c 26 27 .183 70 .706 15 .639 1 .00 64 .71 6

ATOM 3501 O PRO c 26 26, .010 70, ,795 15, .275 1, .00 63. .13 8

ATOM 3502 N VAL c 27 27 .735 69 .560 16 .019 1 .00 61 .55 7

ATOM 3503 CA VAL c 27 26 .937 68, .349 16 .081 1, .00 57, .92 6

ATOM 3504 CB VAL c 27 27. .805 67. .073 15, .948 1, .00 56, .85 6

ATOM 3505 CGI VAL c 27 27. .038 65, ,860 16 .439 1, .00 54, .71 6

ATOM 3506 CG2 VAL c 27 28 .197 66, .872 14 .502 1 .00 54, .24 6

ATOM 3507 C VAL c 27 26 .301 68, .400 17 .452 1 .00 56 .84 6

ATOM 3508 O VAL c 27 26, .987 68. .621 18, .450 1, .00 57, .02 8

ATOM 3509 N ALA c 28 24 .989 68 .228 17 .506 1 .00 56 .11 7

ATOM 3510 CA ALA c 28 24 .302 68, .262 18 .783 1, .00 54 .82 6

ATOM 3511 CB ALA c 28 22, .896 68, .775 18, .600 1, .00 55, .72 6

ATOM 3512 C ALA c 28 24, .282 66, .879 19 .424 1, .00 54, .45 6

ATOM 3513 O ALA c 28 23 .579 65. .972 18 .964 1 .00 54, .53 8

ATOM 3514 N VAL c 29 25 .067 66, .742 20 .488 1 .00 53, .25 7

ATOM 3515 CA VAL c 29 25 .191 65, .503 21, .235 1, .00 51. .65 6

ATOM 3516 CB VAL c 29 26 .676 65, .113 21 .450 1, .00 50, .25 6

ATOM 3517 CGI VAL c 29 26 .770 63, .846 22, .297 1, .00 47. .03 6

ATOM 3518 CG2 VAL c 29 27, .358 64. ,921 20. .108 1. .00 50. .21 6

ATOM 3519 C VAL c 29 24 .549 65. .670 22 .595 1 .00 52. .02 6

ATOM 3520 O VAL c 29 24 .833 66, .615 23 .320 1 .00 51, .40 8

ATOM 3521 N SER c 30 23 .669 64 .745 22 .932 1. .00 53 .81 7

ATOM 3522 CA SER c 30 23 .012 64, .785 24 .214 1 .00 55, .39 6

ATOM 3523 CB SER c 30 21 .495 64 .666 24 .034 1. .00 54 .53 6

ATOM 3524 OG SER c 30 21 .159 63 .462 23 .373 1 .00 56 .88 8

ATOM 3525 C SER c 30 23 .566 63, .614 25, .013 1, .00 55. .69 6

ATOM 3526 O SER c 30 23 .688 62, .504 24, .503 1, .00 56. .19 8

ATOM 3527 N VAL c 31 23 .916 63, .888 26, .261 1, .00 56, .76 7 r Q Cl CS] oo oo r-t <-|

( v H ^ vH so cn sσ cM ro ro ∞ i^ cM rH cn so ^ o^ c m cn o ^ c ^ r- i i s σι o ^ » _ σ ^,^ ιn co so CΛ ^ c_o cn <-H ^ _ M Λ θ '^ c '^ ^ ro Λ -n o so o _-) co c r--i r-- - c> _n rO 'H r-- '-l Ji (^ H in rn cn o n ro vo ^ - ^ t^f t oo o O ^ M ro M M C ro ιH rH ι- o o ) θ cn OT θ o cn o σι ι ω ιn o ι co c - ^ so ιn o r-- ∞ so so so so so so so so io so so in so in -n so so -n in in in in tn tn in in in Ln in in in in in in in in in in in in i^ H H ∞ Ln c!l O (_l <J κl lD (Jl co <--l _ rn oθ - θ rn oθ -n ro co r-t H M MD O pl sf O lO h H -n sJ

^ H H i H ^ N N Pj (si ! M i<i m m n m n rn ii ^ ^ ^ i⁾ ^ ^ ^ i| _n i_i in in i_i -n -n in ifl _n in iD iD io ^ u o u J o o u u o o u u u cj u u o o o o u u u a u a a o u o υ u o o u u u o o cj u o o o u o o a u J u o J O u u u u u o gg b lD W CO W Cn tΛ CΛ ω O ω W W ω W W W H W H H H W H H H W

_ _ . _ _ . , _ H W H W i>< ix t I ^■w l ^■M ^■ K — K — K —W —ffi -W—K K — —K —K ^■M^■ ^ - μU - - - μ -i J - v-l w n —w w - -w- .w- .w.- .t^.Q- i- -q j - h -q j - i- -q

> > > > W W W Λ LΩ W ^ ι^ ιJ μ₄ ι^ ι^ μ₄ _J _^ ι-₄ h h₄ h₄ μ j j Pi fc ft H tf di Cii tli fli ft lli H H H H H H H rt| rt! ι!l| ι< ι!ll <l ι4l H H H H H rt. Q CD Q <! cq U cj O O o u u o 3 u o |g u o o u oo c^ θ v^ c rn ^ ιn o ι oo o θ rH r<ι ro ^ ι vD t--- ∞ o^ o H CM -^ _i ι sθ - oo c^ _{CM C}M m ro M ro rn rn ro ro M ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ i i i -n i in in in i i D SD i i i^ L^ tn -n -n in -n in in in -n in in in in in in Ln in in in in in in in in Lo in in in in -o in in in L^ -^ ro m r ro M m n o ro ro M c^ M rO -^ ro co ro cn cn rn ro c^ rn ro

90 o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o oo o o o o o o o o o o o σ o o o o

_H -H IH IH |H tι _ EH E-i E>ι H E→ E-ι _ ι e _H εH __-i -H -_-> t→ -→ ^

ATOM 3589 CDl ILE C 38 25.630 55.758 44.343 1.00 40.81 6

ATOM 3590 C ILE C 38 28. ,432 51. ,585 44. ,306 1. 00 49. ,67 6

ATOM 3591 O ILE C 38 27. ,890 51. ,083 45. .281 1. ,00 53. ,17 8

ATOM 3592 N LEU C 39 29. ,636 51. ,228 43. .872 1. ,00 51. ,33 7

ATOM 3593 CA LEU C 39 30. ,378 50. ,125 44. .468 1. ,00 53. ,07 6

ATOM 3594 CB LEU C 39 31. .113 49. ,384 43. ,353 1. 00 53. ,88 6

ATOM 3595 CG LEU C 39 30. 167 49. ,000 42. ,215 1. 00 55. ,35 6

ATOM 3596 CDl LEU C 39 30, ,932 48. .308 41, .115 1. ,00 54. .78 6

ATOM 3597 CD2 LEU C 39 29. .053 48. ,097 42. .760 1. .00 54. ,41 6

ATOM 3598 C LEU C 39 31. ,334 50. ,367 45. ,619 1. ,00 53. ,89 6

ATOM 3599 O LEU C 39 31. .386 49. .567 46, ,558 1. .00 53. .73 8

ATOM 3600 N GLU C 40 32. ,124 51. ,426 45. .536 1. ,00 54. ,34 7

ATOM 3601 CA GLU C 40 33. ,058 51. .714 46. ,602 1. ,00 56. ,97 6

ATOM 3602 CB GLU C 40 34. ,446 51. ,211 46. ,271 1. ,00 59. ,79 6

ATOM 3603 CG GLU C 40 34. ,555 49. ,711 46. ,147 1. ,00 67. ,48 6

ATOM 3604 CD GLU C 40 35. .996 49, .266 45, .979 1, .00 70, .43 6

ATOM 3605 OEl GLU C 40 36. .647 49. .719 44, .998 1. ,00 71. ,96 8

ATOM 3606 OE2 GLU C 40 36, .471 48. .476 46, ,832 1, .00 71. .19 8

ATOM 3607 C GLU C 40 33, .125 53. .192 46. ,823 1. .00 57. .35 6

ATOM 3608 O GLU C 40 33, .163 53, .975 45. .886 1. ,00 58. ,85 8

ATOM 3609 N VAL C 41 33. .132 53, .572 48 .084 1 .00 57 .50 7

ATOM 3610 CA VAL C 41 33. .202 54. ,964 48. .440 1. ,00 56. .50 6

ATOM 3611 CB VAL C 41 31. .845 55, ,447 49. .000 1. .00 57. .37 6

ATOM 3612 CGI VAL C 41 31 .972 56. .832 49 .567 1, .00 56, .32 6

ATOM 3613 CG2 VAL c 41 30, .797 55, ,437 47 .894 1. .00 57, .94 6

ATOM 3614 C VAL c 41 34, .289 55, ,098 49 .486 1. .00 55, .27 6

ATOM 3615 O VAL c 41 34, .502 54. .200 50, .300 1. .00 54. .09 8

ATOM 3616 N ASN c 42 34, .994 56. .216 49, .433 1. ,00 55. .74 7

ATOM 3617 CA ASN c 42 36, .053 56, .504 50 .379 1. .00 56, .05 6

ATOM 3618 CB ASN c 42 37, .418 56, .169 49 .787 1. ,00 53, .93 6

ATOM 3619 CG ASN c 42 38, .509 56, .155 50, .833 1. .00 53, .86 6

ATOM 3620 ODl ASN c 42 38 .622 57 .075 51 .634 1, .00 54 .42 8

ATOM 3621 ND2 ASN c 42 39, .325 55, .110 50 .828 1. .00 54, .04 7

ATOM 3622 C ASN c 42 35 .947 57 .994 50 .635 1 .00 58 .42 6

ATOM 3623 O ASN c 42 36, .322 58, .806 49, .786 1. .00 58, .83 8

ATOM 3624 N GLU c 43 35, .408 58, .348 51, .801 1. .00 60, .55 7

ATOM 3625 CA GLU c 43 35 .242 59 .744 52 .163 1. .00 61 .17 6

ATOM 3626 CB GLU c 43 34 .269 59, .874 53 .327 1. .00 63, .37 6

ATOM 3627 CG GLU c 43 33 .932 61 .318 53 .646 1. .00 6 .39 6

ATOM 3628 CD GLU c 43 32 .773 61 .463 54 .616 1, .00 68 .69 6

ATOM 3629 OEl GLU c 43 32 .494 62 .613 55 .019 1, .00 69 .27 8

ATOM 3630 OE2 GLU c 43 32 .142 60 .444 54 .964 1, .00 68 .84 8

ATOM 3631 C GLU c 43 36, .571 60. .391 52, .524 1. ,00 60. ,37 6

ATOM 3632 O GLU c 43 36 .706 61 .611 52 .459 1. .00 59 .71 8

ATOM 3633 N ILE c 44 37 .544 59 .567 52 .903 1, .00 59. .67 7

ATOM 3634 CA ILE c 44 38 .874 60 .051 53 .254 1, .00 60 .12 6

ATOM 3635 CB ILE c 44 39 .727 58 .944 53 .908 1 .00 60 .72 6

ATOM 3636 CG2 ILE c 44 41 .124 59 .469 54 .194 1, .00 61 .61 6

ATOM ^'3637 CGI ILE c 44 39 .081 58 .470 55 .206 1 .00 62 .18 6

ATOM 3638 CDl ILE c 44 39 .142 59 .479 56 .325 1, .00 63 .46 6

ATOM 3639 C ILE c 44 39 .617 60 .514 51 .998 1, . 00 59 .74 6

ATOM 3640 O ILE c 44 40 .255 61 .569 51 .988 1, .00 60 .88 8

ATOM 3641 N THR c 45 39 .540 59 .710 50 .944 1 .00 57 .16 7

ATOM 3642 CA THR c 45 40 .221 60 .022 49 .698 1, .00 54 .13 6

ATOM 3643 CB THR c 45 40 .819 58 .743 49 .056 1 .00 52 .62 6

ATOM 3644 OG1 THR c 45 39 .776 57 .810 48 .773 1, .00 52 .62 8

ATOM 3645 CG2 THR c 45 41 .812 58 .106 49 .985 1 .00 52 .65 6

ATOM 3646 C THR c 45 39 .325 60 .706 48 .675 1, .00 51 .85 6

ATOM 3647 O THR c 45 39 .801 61 .196 47 .664 1, .00 51 .94 8

ATOM 3648 N ASN c 46 38 .029 60 .736 48 .933 1 .00 51 .51 7

ATOM 3649 CA ASN c 46 37 .106 61 .367 48 .002 1, .00 52 .39 6 ATOM 3650 CB ASN c 46 37.,420 62.,856 47,,890 1.,00 54.,02 6

ATOM 3651 CG ASN c 46 36. 525 63. ,703 48. ,766 1. 00 56. ,29 6

ATOM 3652 ODl ASN c 46 36. 877 64. ,821 49. 132 1. 00 59. 35 8

ATOM 3653 ND2 ASN c 46 35. .357 63. .182 49. ,093 1. ,00 53. .30 7

ATOM 3654 C ASN c 46 37. ,143 60. .711 46. ,618 1. ,00 52. ,56 6

ATOM 3655 O ASN c 46 37. ,269 61. ,376 45. ,587 1. 00 51. ,60 8

ATOM 3656 N GLU c 47 37. ,013 59. .392 46. .610 1. ,00 51. ,63 7

ATOM 3657 CA GLU c 47 37. ,023 58. .633 45. .376 1. ,00 50. .56 6

ATOM 3658 CB GLU c 47 38. ,307 57. .805 45. .300 1. ,00 49. ,50 6

ATOM 3659 CG GLU c 47 39. ,566 58. .650 45. ,210 1. 00 49. ,79 6

ATOM 3660 CD GLU c 47 40, ,823 57, ,810 45, .227 1. .00 51. .38 6

ATOM 3661 OEl GLU c 47 40. ,741 56. .621 44. ,860 1. 00 52. ,93 8

ATOM 3662 OE2 GLU c 47 41. ,892 58. ,339 45. .595 1. ,00 51. ,30 8

ATOM 3663 C GLU c 47 35. ,793 57, ,734 45, ,314 1. ,00 48. .78 6

ATOM 3664 O GLU c 47 35. ,403 57. .133 46. .300 1. ,00 48. .46 8

ATOM 3665 N VAL c 48 35. ,178 57. .654 44. .147 1. .00 47. ,95 7

ATOM 3666 CA VAL c 48 33. ,998 56. .834 43. .993 1. ,00 49. ,71 6

ATOM 3667 CB VAL c 48 32. .768 57, .701 43. .736 1. ,00 50, .43 6

ATOM 3668 CGI VAL c 48 31. ,549 56. ,834 43. ,578 1. ,00 53. .94 6

ATOM 3669 CG2 VAL c 48 32. .567 58. .645 44, .869 1. ,00 52. .35 6

ATOM 3670 C VAL c 48 34. .130 55. .838 42, .850 1. .00 49. ,77 6

ATOM 3671 O VAL c 48 34. .686 56, .146 41. ,802 1. ,00 49. ,93 8

ATOM 3672 N ASP c 49 33. .615 54, .636 43, ,068 1. ,00 49. .86 7

ATOM 3673 CA ASP c 49 33. .646 53. ,595 42. .061 1. .00 49. ,59 6

ATOM 3674 CB ASP c 49 34. .261 52. .331 42, ,644 1. .00 51. .71 6

ATOM 3675 CG ASP c 49 34. .714 51. .366 41. .580 1. .00 51. .64 6

ATOM 3676 ODl ASP c 49 33 .992 51 .233 40 .581 1, .00 50, .25 8

ATOM 3677 OD2 ASP c 49 35. .777 50. .736 41. .748 1. ,00 51. .89 8

ATOM 3678 C ASP c 49 32. .181 53. ,382 41, .728 1, ,00 49. .00 6

ATOM 3679 O ASP c 49 31, .437 52, .818 42, .52.4 1, ,00 51, .14 8

ATOM 3680 N VAL c 50 31. .770 53, .840 40, .551 1, ,00 48, .30 7

ATOM 3681 CA VAL c 50 30. .374 53, .757 40, .147 1. ,00 48. ,89 6

ATOM 3682 CB VAL c 50 29. .755 55 .185 40, .167 1. .00 51, .49 6

ATOM 3683 CGI VAL c 50 30 .212 55 .964 38 .944 1, .00 50, .49 6

ATOM 3684 CG2 VAL c 50 28. .248 55, .120 40. .223 1, ,00 53. .32 6

ATOM 3685 C VAL c 50 30. .130 53, .122 38, .771 1, .00 47. ,56 6

ATOM 3686 O VAL c 50 31 .012 53, .080 37, .928 1, .00 49. .11 8

ATOM 3687 N VAL c 51 28, .917 52, .621 38, .574 1. ,00 44, .81 7

ATOM 3688 CA VAL c 51 28 .484 52 .003 37, .324 1, ,00 43, .09 6

ATOM 3689 CB VAL c 51 28 .003 50 .542 3 .539 1, .00 41 .28 6

ATOM 3690 CGI VAL c 51 27, .355 50, .017 36, .267 1, ,00 37, .45 6

ATOM 3691 CG2 VAL c 51 29, .157 49, .659 37, .953 1, ,00 36. ,77 6

ATOM 3692 C VAL c 51 27 .300 52 .817 36 .781 1, .00 44 .98 6

ATOM 3693 O VAL c 51 26 .385 53 .163 37 .522 1, .00 46 .72 8

ATOM 3694 N PHE c 52 27 .299 53, .113 35 .490 1, .00 44, .48 7

ATOM 3695 CA PHE c 52 26 .206 53 .883 34 .937 1, .00 45 .00 6

ATOM 3696 CB PHE c 52 26 .469 55 .352 35 .210 1 .00 44 .94 6

ATOM 3697 CG PHE c 52 27 .729 55 .857 34 .587 1 .00 44 .74 6

ATOM 3698 CDl PHE c 52 27 .735 56 .327 33 .278 1 .00 44 .14 6

ATOM 3699 CD2 PHE c 52 28 .921 55 .841 35 .299 1 .00 44 .43 6

ATOM 3700 CEl PHE c 52 28 .908 56 .771 32 .690 1, .00 45, .23 6

ATOM 3701 CE2 PHE c 52 30 .102 56 .284 34 .722 1, .00 41 .52 6

ATOM 3702 CZ PHE c 52 30 .098 56 .751 33 .415 1 .00 42 .14 6

ATOM 3703 C PHE c 52 26 .048 53 .663 33 .443 1, .00 47 .73 6

ATOM 3704 O PHE c 52 26 .932 53 .102 32 .798 1 .00 49 .84 8

ATOM 3705 N TRP c 53 24 .918 54 .099 32 .895 1 .00 46 .73 7

ATOM 3706 CA TRP c 53 24 .684 53 .985 31 .471 1 .00 47 .02 6

ATOM 3707 CB TRP c 53 23 .251 53 .595 31 .175 1, .00 46, .36 6

ATOM • 3708 CG TRP c 53 22 .915 52 .221 31 .552 1 .00 48 .76 6

ATOM 3709 CD2 TRP c 53 21 .615 51 .636 31 .534 1 .00 50 .65 6

ATOM 3710 CE2 TRP c 53 21 .748 50 .311 32 .002 1 .00 49 .66 6 ATOM 3711 CE3 TRP C 53 20.342 52.106 31.170 1.00 51.64 6

ATOM 3712 CDl TRP C 53 23. 765 51. 259 32. 008 1. 00 48. 94 6

ATOM 3713 NEl TRP C 53 23. 073 50. 107 32. 284 1. 00 48. 58 7

ATOM 3714 CZ2 TRP C 53 20. 659 49. 448 32. 120 1. 00 50. 24 6

ATOM 3715 CZ3 TRP C 53 19. 258 51. 250 31. 286 1. 00 51. 60 6

ATOM 3716 CH2 TRP C 53 19. 424 49. 935 31. 759 1. 00 52. ,14 6

ATOM 3717 C TRP C 53 24. 940 55. ,339 30. 862 1. 00 48. ,39 6

ATOM 3718 O TRP C 53 24. 234 56. 290 31. 156 1. 00 50. ,70 8

ATOM 3719 N GLN C 54 25. 946 55. 429 30. 010 1. 00 49. ,71 7

ATOM 3720 CA GLN C 54 26. 265 56. ,691 29. ,378 1. 00 50. ,29 6

ATOM 3721 CB GLN C 54 27. 759 56. 749 29. 053 1. 00 50. ,27 6

ATOM 3722 CG GLN C 54 28. 231 58. ,111 28. 587 1. 00 54. ,00 6

ATOM 3723 CD GLN C 54 29. ,710 58. .344 28. ,853 1. 00 55. 07 6

ATOM 3724 OEl GLN C 54 30. 172 58. 241 29. 988 1. 00 53. 42 8

ATOM 3725 NE2 GLN C 54 30. ,458 58, ,667 27. ,805 1. ,00 57. ,05 7

ATOM 3726 C GLN C 54 25. ,415 56. .797 28. ,125 1. ,00 50. ,70 6

ATOM 3727 O GLN C 54 25. .886 56, .617 27, .004 1. ,00 52. .15 8

ATOM 3728 N GLN C 55 24. ,138 57. ,069 28. ,345 1. 00 51. ,37 7

ATOM 3729 CA GLN C 55 23. ,169 57. ,205 27. 272 1. 00 54. ,41 6

ATOM 3730 CB GLN C 55 21. ,786 57. .326 27. .897 1. 00 57. ,18 6

ATOM 3731 CG GLN C 55 20. ,667 57. ,648 26, ,948 1. ,00 64. ,94 6

ATOM 3732 CD GLN C 55 19. ,313 57, .472 27, ,617 1. ,00 70. ,65 6

ATOM 3733 OEl GLN C 55 19. ,154 57, ,760 28. ,817 1. 00 73. ,87 8

ATOM 3734 NE2 GLN c 55 18, .325 56, .997 26. .849 1. .00 72, .08 7

ATOM 3735 C GLN c 55 23, .509 58, .419 26, ,396 1, .00 53. .13 6

ATOM 3736 O GLN c 55 23, .296 59, .569 26, .^'779 1, .00 54. .85 8

ATOM 3737 N THR c 56 24 .044 58 .148 25 .211 1, .00 50 .27 7

ATOM 3738 CA THR c 56 24, .455 59, .193 24, .290 1. .00 48, .20 6

ATOM 3739 CB THR c 56 25, .916 59, .019 23, ,905 1. .00 47, .97 6

ATOM 3740 OG1 THR c 56 26, .693 58, .795 25. .085 1. .00 51. .04 8

ATOM 3741 CG2 THR c 56 26, .431 60 .243 23 ,219 1, ,00 46 .01 6

ATOM 3742 C THR c 56 23 .633 59 .162 23 .023 1. .00 49 .71 6

ATOM 3743 O THR c 56 23, .216 58 .095 22 .568 1, .00 49 .78 8

ATOM 3744 N THR c 57 23 .393 60 .340 22 .454 1. .00 49, .24 7

ATOM 3745 CA THR c 57 22. .619 60 .436 21, .221 1. .00 49 .62 6

ATOM 3746 CB THR c 57 21 .122 60 .592 21 .501 1, .00 49 .45 6

ATOM 3747 OG1 THR c 57 20 .640 59 .440 22 .206 1, .00 49 .55 8

ATOM 3748 CG2 THR c 57 20 .368 60 .722 20 .191 1 .00 51 .01 6

ATOM 3749 C THR c 57 23, .057 61, .608 20, .368 1. .00 48, .68 6

ATOM 3750 O THR c 57 23, .423 62, .649 20, .888 1. .00 51. .05 8

ATOM 3751 N TRP c 58 23 .033 61 .428 19 .056 1 .00 45 .80 7

ATOM 3752 CA TRP c 58 23 .415 62 .487 18 .145 1 .00 45 .33 6

ATOM 3753 CB TRP c 58 24 .934 62 .702 18 .146 1 .00 44 .23 6

ATOM 3754 CG TRP c 58 25 .733 61 .584 17 .556 1, .00 45 .68 6

ATOM 3755 CD2 TRP c 58 26 .221 60 .428 18 .241 1 .00 43 .51 6

ATOM 3756 CE2 TRP c 58 26 .896 59 .642 17 .296 1 .00 41 .95 6

ATOM 3757 CE3 TRP c 58 26 .150 59 .983 19 .566 1 .00 44 .75 6

ATOM 3758 CDl TRP c 58 26 .120 61 .453 16 .264 1 .00 41 .99 6

ATOM 3759 NEl TRP c 58 26 .818 60 .292 16 .097 1 .00 43 .07 7

ATOM 3760 CZ2 TRP c 58 27 .498 58 .436 17 .625 1 .00 42 .44 6

ATOM 3761 CZ3 TRP c 58 26 .748 58 .778 19 .894 1 .00 45 .66 6

ATOM 3762 CH2 TRP c 58 27 .414 58 .020 18 .926 1 .00 44 .08 6

ATOM 3763 C TRP c 58 22 .915 62 .107 16 .772 1 .00 46 .80 6

ATOM 3764 O TRP c 58 22 .315 61 .054 16 .603 1 .00 45 .26 8

ATOM 3765 N SER c 59 23 .157 62 .959 15 .788 1 .00 50 .21 7

ATOM 3766 CA SER c 59 22 .663 62 .684 14 .452 1 .00 53 .47 6

ATOM 3767 CB SER c 59 21 .536 63 .657 14 .128 1 .00 54 .42 6

ATOM 3768 OG SER c 59 20 .707 63 .146 13 .104 1 .00 59 .88 8

ATOM 3769 C SER c 59 23 .733 62 .752 13 .376 1 .00 54 .85 6

ATOM 3770 O SER c 59 24 .541 63 .682 13 .343 1 .00 54 .12 8

ATOM 3771 N ASP C 60 23 .727 61 .745 12 .503 1 .00 57 .21 7 to to to ;_> to to to to ' to ; to to ;_p ;_y ;_y to ' to 3 ι-3 ι-3 3 β ^μ3 β β ι-3 β ι- !-3 β β t-3 ι-3 H β t-3 β β β β β β ιβ <-3 B ι-3 B β ιβ ι-3 ι- !^ β H ι-3 β ι-3 β OO O O O O O O OO OO O OO O O O O O O O O O O O O O O O O O O OO OO O O O O O O OO O O O O O Q O O Q O OOO OO gggggggggggggggggggg gggggggggggggggggggggggggggggggggggggggg ω L ω ω j LO J Lo ω Lϋ O L L o i o ω ω ω o ω ω ω ω j ω ω ω ω j ω ω ω o ω ω w L L LO J L

∞ θ3 ra co ra o3 o m ra ω co ra (B ∞ αj B tD C_) αι co co o3 co tD (» (i! (_) ∞ (D ) tD co α) >J -o ι ^ ι i J ^ l l -O --J -J --J ~O --J --J --J l -O --0 --J ~J --0 l l -O ~J ωω oJ ww ωto ttoO -tsOJ KtOj e-O ttsoJ Mw tisoO Mω tMo p pH Rp Pp-' p μp-' pμ^ . μ-' o o σ o O oO oO oO oO oO σO oO LoO SoO so so SO VO S O lO 00 00 00 C0 00 00 00 00 C0 00 -O -J l ^] --J I -~J ( μ o «ι o] ! σ uι _- ω w p o ιo o3 ^ (iι uι ^ ω -θ p o ιo ctι j σi ui ^ ω t o io ω o m ui ^ I _ μ θ lO CO -J Ol Ul *, U IO P O l_3 (B sl CIHjl ^ U l

2 O Ω a o Ω a Ω a O Ω Ω Ω Ω ^ Ω Ω Ω Ω Ω Ω Ω ^ O Ω Ω Ω -SJ O Ω Ω Ω Ω Ω Ω ≥I O Ω Ω O Ω Ω S O Ω ≥! Ω a Ω Ω Ω Ω a O Ω O O Ω Ω 3 U Ω to K N N B O B M O O l!) l ω > α α Ω c Ω Ω C N H α Ω Cd J α α Ω ω

M U lsl P P l M tO to μ-> to μ-> d lo -> to j->

CO ! | < β π3 ι-3 3 β ι-3 β β ι-3 ι-3 i-3 β β >-3 to to to |> to lr^l _r^, ir^< t t t-^| t-^| _r^, ι-3 ι-3 ^ β ^μ3 i-a β ^ ;μ ; !_o ' !f to ;_y ;y ^, ' ! !_=_ ^{ι |} !t ^' tS ^' ccoα tcoo LcoO ccoo coo cc _o cco Λ . p. ^._ d p pd p pd a d pd d F !^¹ t^^, !^^l E-^, BBBHBBBBSΪKKE K a pa pd pd pd pd pd pd pd pd pd co co co co co co c

Pd a a a a a a a a w ^ id fl w w ^ fl ) 'd 'ϋ w j fl ^ α G α d α _ι α ^ ^ ^ ^ ^ p] » n Q n o o Ω Ω o n o n w ^,ι) ^,d ^|j ^|fl ^,t) ^|

Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω n Ω n Ω Ω Ω Ω Ω Ω O Ω Ω O Ω O Ω O Ω Ω Ω Ω O Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω n Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω

P H p μ μ p μ H H H H p t μ μ H p μ p p μ H H - ) -) _O ts) t ts) M t l - -S) t t W ls) t _O ) ( M t p p p to _o to ιo to _o _ _o ts) _o _o ι ω ui MJ i J ^ ui tu cn Ho o iii ^i j iD co oj iii io co iii o o o p - _o σι Ui ui ι^ ι*) _^ uι *> ^ -J σι uι j- M ι lo oo io o μ tO -O w u xKΛ m ui i

OT __^ α_> θΛ rø L co M - . Ln c μ^J o o μ-^Λ .l^ o o ι _ Lπ Lo ι o oo o σι tsJ -j σ .^ oo o Lo ^ Lπ cn co M .t^ u o .-^ oo υ - ι co to cn ω -θ __^ Ln ιi-» co cn o o ^j

Lπ μ^j M L Lπ αi L w oo o ∞ to ι )o μ-¹ Lπ Lπ L_π t -J tø i£i Lπ o μ-^> n -ⁱ -j o Lπ ι_o ι w

Lπ L_π ui Lπ Lπ ⁽_π Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ Lπ ui Lπ (_π Lo tθ θ Lπ Lπ Lπ π Lπ Lπ Lπ Lπ t ω p^ Co ω t> J L θ Lπ c^ -j -j o --J CX) Lπ cn n c^

U ϋl siI tLoJ tCOμ'oO Uo μμUui -W rt|i5 WW iliD)θUDI fHi> ιUιil--O pP MJ iliO)UUJtlSo μpoo WwιlOooO t(DDilit)l μP iS!D) μpωiIItCoO ιU_ιloU lD O lD Ui ω μ l Ui m σι υWi μP o ^ ω σi H ω p so D *. uι μ ^ ω m m ω p p c!i θ) [D uι ω ιi- ω oi ιi- p o co co ιii j co p - iΛ ω ^ ι i ^ _ μ ιo ιo p ι^ «] oι ω -J a) p ω j ^j oo ra p t p ui w cn p uHD -J P m ι_ι o ^ p o u μ ω ι_π ι ^ o m io o m -J o ci) io p u) i! ι o co uι θ vi (D ()D iύ io ω ιo ui i uι «) αι ω m u o m to μ Ln -J L oo O -j ii^ -sj -J

_ ι ι_n ω p _ ^ cD o ω w j p o χi ιn o m o m m u ii ιii ^ uι ι o p ω p -θ J P (_ι ω ω w ιo _o o o o is) o o _o ^ o uι ω σi -θ ω -i p ιo ^ ιli ^[» u ι P ι(- o m ω m ι_ι D U⁾ ιi- ω u (i io ^j o3 o iΛ m co uι _o o i ιii ι_i ω m w p t M i)i p co uι uι iJ ^ w ι^ ϋ _ _- ιo fr co -θ si ra ι|i i_n iD ^ ω [» ιli ι^ ι o uι iΛ P o s) i i vj NJ io ω o p p _i p ω m σι ω o3 Ui ω ijι p ι vo ^ αj ra μ-^s μ-^{s j} μ^ι μ-^ι μ μ-^ι μ-^ι μ^j μ-^l _-> Pⁱ μ-> μ-^ι -^ι μ-> μ-ⁱ μ-^ι μ-^ι μ-> μⁱ μ-> μ-^ι μ-> t-^y ι-» μ-» μ-> μ-^s μ-^l μ-» μ-' μ-^ι μ-' H> μ-¹ μ-> μ-> μ-> μ-> μ-> μ-^ι μ^Λ μ-> μ-^ι μ-^ι μ^Λ μ-^ι μ-> μ-> .-^Λ μ-' μ-> μ

O O O O O O O O O CD O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O D O O O O O O O O O O O O o o o o o o o σ o o o o o o σ o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o σ o o o

O O _^J 1 CO ui ui ^ σi m m m m m tΛ m ro w co co ^ ^ m ω ui ιf^ ι o

Lπ ω -J θ oo W ι -J -^l ι co c --J » c_Λ

ATOM 3833 CA SER C 67 13.166 52.647 4.,920 1.00 73.,52 6

ATOM 3834 CB SER C 67 13. 451 52. ,759 6. 411 1. 00 72. ,63 6

ATOM 3835 OG SER C 67 12. ,985 53. ,994 6. ,914 1. ,00 70. .04 8

ATOM 3836 C SER C 67 11. ,684 52. ,469 4. ,702 1. ,00 75. ,29 6

ATOM 3837 O SER C 67 11. 010 51. 788 5. 493 1. 00 75. ,31 8

ATOM 3838 N SER C 68 11. ,165 53. ,077 3. ,639 1. ,00 77. ,57 7

ATOM 3839 CA SER C 68 9. ,739 52. ,957 3. ,356 1. 00 78. ,39 6

ATOM 3840 CB SER C 68 9. .327 53. .874 2. ,187 1. .00 77. ,79 6

ATOM 3841 OG SER C 68 10. ,010 53, ,570 0. .983 1. ,00 77. .16 8

ATOM 3842 C SER C 68 9. .398 51. ,498 3. .051 ,1. ,00 78. .91 6

ATOM 3843 O SER C 68 8. .242 51. ,165 2. .802 1. ,00 78. .88 8

ATOM 3844 N HIS C 69 10. ,415 50. ,634 3. ,090 1. ,00 80. .17 7

ATOM 3845 CA HIS C 69 10, .252 49. ,197 2. ,824 1. .00 81. .55 6

ATOM 3846 CB HIS C 69 10. ,307 48. ,935 1. ,319 1. ,00 84. .67 6

ATOM 3847 CG HIS C 69 9. .327 49. .755 0. .542 1. ,00 88. .75 6

ATOM 3848 CD2 HIS C 69 8. .119 49. ,436 0. ,014 1. ,00 89. .38 6

ATOM 3849 NDl HIS C 69 9, .479 51. .115 0, .359 1. .00 89, .98 7

ATOM 3850 CEl HIS C 69 8, .405 51, .600 -0, .239 1. .00 91, .29 6

ATOM 3851 NE2 HIS C 69 7. .564 50. ,602 -0. ,458 1. ,00 91, .72 7

ATOM 3852 C HIS c 69 11. .363 48, .406 3, .514 1. .00 80, .62 6

ATOM 3853 O HIS c 69 11, .740 47. .318 3. .072 1. .00 79, .15 8

ATOM 3854 N SER c 70 11 .867 48, .961 4 .614 1, ,00 79 .62 7

ATOM 3855 CA SER c 70 12, ,950 48. .341 5. .355 1. .00 77, .30 6

ATOM 3856 CB SER c 70 14 .262 48, .818 4. .739 1. .00 77 .47 6

ATOM 3857 OG SER c 70 14, .107 48, .991 3, .336 1. .00 74 .00 8

ATOM 3858 C SER c 70 12, .880 48. ,746 6. ,836 1. ,00 76. .56 6

ATOM 3859 O SER c 70 12, ,168 49. .686 7. .193 1. ,00 77, .11 8

ATOM 3860 N PRO c 71 13, ,587 48, .014 7, .726 1. .00 76, .29 7

ATOM 3861 CD PRO c 71 14 .305 46, .733 7, .544 1. ,00 75 .52 6

ATOM 3862 CA PRO c 71 13, .538 48, .401 9, .143 1. .00 74 .74 6

ATOM 3863 CB PRO c 71 14 .366 47 .322 9. .843 1, .00 75 .26 6

ATOM 3864 CG PRO c 71 14, .241 46, .124 8, .936 1. .00 75 .64 6

ATOM 3865 C PRO c 71 14, .202 49. .771 9, .235 1. .00 73 .61 6

ATOM 3866 O PRO c 71 15 .042 50 .125 8. .401 1, .00 72 .22 8

ATOM 3867 N ASP c 72 13 .828 50, ,537 10. .247 1. ,00 72, .60 7

ATOM 3868 CA ASP c 72 14 .377 51, .869 10, .414 1. .00 70 .96 6

ATOM 3869 CB ASP c 72 13 .277 52, .795 10, .899 1. .00 75 .25 6

ATOM 3870 CG ASP c 72 11 .919 52 .353 10 .415 1, .00 78 .33 6

ATOM 3871 ODl ASP c 72 11, .633 52, .512 9, .199 1, . 00 79, .88 8

ATOM 3872 OD2 ASP c 72 11, .150 51, .821 11, .256 1. .00 79 .56 8

ATOM 3873 C ASP c 72 15 .519 51 .835 11, .411 1. ,00 68 .36 6

ATOM 3874 O ASP c 72 16 .046 52, .887 11 .799 1. .00 66 .88 8

ATOM 3875 N GLN c 73 15 .883 50 .625 11 .838 1 .00 63 .81 7

ATOM 3876 CA GLN c 73 17 .001 50, .485 12, .756 1, . 00 61 .20 6

ATOM 3877 CB GLN c 73 16 .537 50 .494 14 .191 1 .00 61 .12 6

ATOM 3878 CG GLN c 73 16 .121 51 .802 14 .749 1, .00 62 .71 6

ATOM 3879 CD GLN c 73 15 .665 51 .603 16 .163 1, .00 64 .60 6

ATOM 3880 OEl GLN c 73 14 .784 50 .779 16 .421 1, .00 67 .49 8

ATOM 3881 NE2 GLN c 73 16 .267 52 .329 17 .099 1, .00 66 .00 7

ATOM 3882 C GLN c 73 17 .842 49 .232 12 .583 1 .00 59 .70 6

ATOM 3883 O GLN c 73 17 .350 48 .167 12 .213 1 .00 61 .26 8

ATOM 3884 N VAL c 74 19 .122 49 .369 12 .893 1 .00 56 .05 7

ATOM 3885 CA VAL c 74 20 .050 48 .260 12 .825 1 .00 52 .11 6

ATOM 3886 CB VAL c 74 20 .736 48 .177 11 .454 1, .00 52 .42 6

ATOM 3887 CGI VAL c 74 19 .732 47 .788 10 .397 1 .00 51 .61 6

ATOM 3888 CG2 VAL c 74 21 .376 49 .507 11 .112 1 .00 52 .96 6

ATOM 3889 C VAL c 74 21 .095 48 .498 13 .891 1 .00 50 .29 6

ATOM 3890 O VAL c 74 21 .277 49 .626 14 .332 1 .00 49 .79 8

ATOM 3891 N SER c 75 21 .754 47 .431 14 .323 1 .00 48 .56 7

ATOM 3892 CA SER c 75 22 .809 47 .533 15 .318 1 .00 45 .56 6

ATOM 3893 CB SER c 75 22 .784 46 .337 16 .257 1, .00 43 .40 6 ATOM 3894 OG SER C 75 21.818 46.521 17.269 1.00 43.99 8

ATOM 3895 C SER C 75 24. 146 47. 611 14. 595 1. 00 44. 84 6

ATOM 3896 O SER C 75 24. 519 46. 703 13. 858 1. 00 47. 60 8

ATOM 3897 N VAL C 76 24. 858 48. 712 14. 811 1. 00 43. 51 7

ATOM 3898 CA VAL C 76 26. 140 48. 941 14. 165 1. 00 42. 84 6

ATOM 3899 CB VAL C 76 26. 122 50. 273 13. 412 1. 00 41. 76 6

ATOM 3900 CGI VAL C 76 27. 441 50. 504 12. 741 1. 00 42. 71 6

ATOM 3901 CG2 VAL C 76 25. 003 50. 279 12. 403 1. 00 40. 70 6

ATOM 3902 C VAL C 76 27. 294 48. 961 15. 153 1. 00 42. ,64 6

ATOM 3903 O VAL C 76 27. 194 49. 542 16. 227 1. 00 45. ,77 8

ATOM 3904 N PRO C 77 28. 409 48. 313 14. 812 1. 00 41. 78 7

ATOM 3905 CD PRO C 77 28. 644 47. 345 13. 737 1. 00 41. 15 6

ATOM 3906 CA PRO c 77 29. ,532 48. 326 15. 748 1. 00 41. ,64 6

ATOM 3907 CB PRO c 77 30. ,527 47. 370 15. 108 1. 00 40. ,47 6

ATOM 3908 CG PRO c 77 29. ,654 46. ,432 14. ,379 1. 00 42. ,43 6

ATOM 3909 C PRO c 77 30. ,074 49. ,746 15. ,860 1. 00 41. ,29 6

ATOM 3910 O PRO c 77 30. .123 50. ,489 14. .881 1. 00 38. .61 8

ATOM 3911 N ILE c 78 30. .469 50. ,111 17. ,070 1. 00 41, .82 7

ATOM 3912 CA ILE c 78 31. ,000 51. ,433 17. ,359 1. 00 41. ,93 6

ATOM 3913 CB ILE c 78 31. ,439 51. ,489 18. ,837 1. 00 42. ,16 6

ATOM 3914 CG2 ILE c 78 32. .370 52. ,634 19. ,107 1. 00 42. .14 6

ATOM 3915 CGI ILE c 78 30. .193 51. ,601 19, ,696 1. ,00 44, .77 6

ATOM 3916 CDl ILE c 78 29. .251 52, .676 19. .216 1. ,00 44, .16 6

ATOM 3917 C ILE c 78 32, .149 51, .813 16, .450 1. .00 42, .57 6

ATOM 3918 O ILE c 78 32, ,287 52. ,963 16. .063 1. 00 45. ,18 8

ATOM 3919 N SER c 79 32. .963 50. .829 16. .100 1, ,00 43. .18 7

ATOM 3920 CA SER c 79 34 .120 51. .030 15 .241 1, .00 43 .52 6

ATOM 3921 CB SER c 79 34. .969 49. .768 15, .242 1. ,00 43. .74 6

ATOM 3922 OG SER c 79 34, .189 48, .637 14 .910 1, .00 43, .50 8

ATOM 3923 C SER c 79 33, .810 51, .415 13, .804 1. ,00 43, .41 6

ATOM 3924 O SER c 79 34 .698 51, .838 13 .082 1, ,00 44 .10 8

ATOM 3925 N SER c 80 32, .562 51, .264 13, .380 1. .00 43 .62 7

ATOM 3926 CA SER c 80 32. .180 51, .604 12, .012 1. .00 44. .83 6

ATOM 3927 CB SER c 80 31 .260 50 .534 11 .441 1, .00 44 .21 6

ATOM 3928 OG SER c 80 31, .915 49 .284 11 .380 1, .00 52 .55 8

ATOM 3929 C SER c 80 31 .482 52 .956 11 .908 1 .00 46 .57 6

ATOM 3930 O SER c 80 31 .050 53 .355 10 .829 1, .00 46 .16 8

ATOM 3931 N LEU c 81 31 .366 53, .649 13 .035 1, .00 46 .49 7

ATOM 3932 CA LEU c 81 30 .720 54 .952 13 .080 1, .00 45 .86 6

ATOM 3933 CB LEU c 81 29 .467 54 .891 13 .935 1, .00 45 .00 6

ATOM 3934 CG LEU c 81 28 .421 53 .827 13 .653 1 .00 46 .58 6

ATOM 3935 CDl LEU c 81 27 .488 53 .701 14 .839 1 .00 45 .04 6

ATOM 3936 CD2 LEU c 81 27 .667 54 .198 12 .405 1 .00 47 .69 6

ATOM 3937 C LEU c 81 31 .645 55 .973 13 .718 1, .00 46 .18 6

ATOM 3938 O LEU c 81 32 .636 55 .613 14 .355 1 .00 50 .36 8

ATOM 3939 N TRP c 82 31 .323 57 .249 13 .536 1 .00 43 .58 7

ATOM 3940 CA TRP c 82 32 .086 58 .303 14 .161 1 .00 39 .79 6

ATOM 3941 CB TRP c 82 31 .860 59 .639 13 .463 1 .00 41 .96 6

ATOM 3942 CG TRP c 82 32 .342 60 .817 14 .278 1 .00 44 .12 6

ATOM 3943 CD2 TRP c 82 31 .577 61 .569 15 .230 1 .00 44 .19 6

ATOM 3944 CE2 TRP c 82 32 .453 62 .504 15 .823 1 .00 43 .39 6

ATOM 3945 CE3 TRP c 82 30 .234 61 .540 15 .645 1 .00 44 .58 6

ATOM 3946 CDl TRP c 82 33 .611 61 .318 14 .327 1 .00 43 .74 6

ATOM 3947 NEl TRP c 82 33 .686 62 .327 15 .252 1 .00 44 .54 7

ATOM 3948 CZ2 TRP c 82 32 .033 63 .405 16 .809 1 .00 42 .68 6

ATOM 3949 CZ3 TRP c 82 29 .818 62 .430 16 .623 1 .00 43 .22 6

ATOM 3950 CH2 TRP c 82 30 .717 63 .352 17 .195 1 .00 43 .77 6

ATOM 3951 C TRP c 82 31 .426 58 .348 15 .514 1 .00 40 .00 6

ATOM 3952 0 TRP c 82 30 .219 58 .174 15 .619 1 .00 39 .36 8

ATOM 3953 N VAL c 83 32 .201 58 .574 16 .557 1 .00 40 .23 7

ATOM 3954 CA VAL c 83 31 .626 58 .649 17 .887 1 .00 39 .34 6 ATOM 3955 CB VAL C 83 31.891 57.,325 18.,657 1.00 38.82 6

ATOM 3956 CGI VAL C 83 31. 587 57. 479 20. 109 1. 00 39. 50 6

ATOM 3957 CG2 VAL C 83 31. 021 56. 219 18. 087 1. 00 38. 81 6

ATOM 3958 C VAL C 83 32. 205 59. ,860 18. ,624 1. 00 40. 30 6

ATOM 3959 O VAL C 83 33. 365 60. 222 18. 428 1. 00 41. 45 8

ATOM 3960 N PRO C 84 31. 386 60. 528 19. 451 1. 00 38. 82 7

ATOM 3961 CD PRO C 84 29. ,948 60. ,288 19. ,644 1. 00 40. 83 6

ATOM 3962 CA PRO C 84 31. ,812 61. ,698 20. ,220 1. 00 36. 19 6

ATOM 3963 CB PRO C 84 30. ,580 62. ,022 21. ,058 1. 00 37. ,66 6

ATOM 3964 CG PRO C 84 29. ,479 61. ,609 20. ,201 1. ,00 39. ,39 6

ATOM 3965 C PRO C 84 32. 999 61. ,358 21. ,098 1. 00 34. 25 6

ATOM 3966 O PRO c 84 32. 987 60. ,351 21. ,788 1. 00 35. 16 8

ATOM 3967 N ASP c 85 34. ,016 62, .206 21. ,093 1. .00 33. .39 7

ATOM 3968 CA ASP c 85 35. ,192 61. .949 21. ,909 1. ,00 34. ,67 6

ATOM 3969 CB ASP c 85 36, .423 62. .588 21. .270 1. .00 35. ,95 6

ATOM 3970 CG ASP c 85 36. .260 64. .056 21. ,046 1. ,00 35. ,70 6

ATOM 3971 ODl ASP c 85 35. ,159 64. .468 20, ,662 1. 00 34. ,85 8

ATOM 3972 OD2 ASP c 85 37. .234 64, .798 21, ,238 1. .00 38. .52 8

ATOM 3973 C ASP c 85 35. .005 62, .452 23. .326 1. .00 36. .34 6

ATOM 3974 O ASP c 85 35. .806 63. .229 23, .841 1. ,00 39, ,41 8

ATOM 3975 N LEU c 86 33. .941 61. .978 23. .962 1. .00 36. ,11 7

ATOM 3976 CA LEU c 86 33, .609 62. .385 25, .315 1, .00 36, .00 6

ATOM 3977 CB LEU c 86 32. .208 61, .904 25, .678 1. ,00 35, .07 6

ATOM 3978 CG LEU c 86 31, .089 62, .464 24, .806 1. .00 36, .71 6

ATOM 3979 CDl LEU c 86 29, .752 61, .912 25, .240 1, ,00 31, ,87 6

ATOM 3980 CD2 LEU c 86 31. ,112 63, ,974 24. .910 1. .00 35. ,41 6

ATOM 3981 C LEU c 86 34 .585 61 .870 26, .337 1, ,00 36, .89 6

ATOM 3982 O LEU c 86 35 .147 60 .795 26 .189 1, .00 38, .19 8

ATOM 3983 N ALA c 87 34, ,773 62, .648 27, .391 1. .00 38, .71 7

ATOM 3984 CA ALA c 87 35, .672 62 .268 28, .461 1, .00 38. ,06 6

ATOM 3985 CB ALA c 87 37 .045 62 .838 28, .200 1. ,00 35. .59 6

ATOM 3986 C ALA c 87 35 .119 62 .799 29 .772 1, .00 38. .10 6

ATOM 3987 O ALA c 87 34 .586 63 .891 29 .815 1, .00 37 .91 8

ATOM 3988 N ALA c 88 35 .217 62 .013 30 .833 1 .00 39 .52 7

ATOM 3989 CA ALA c 88 34 .756 62 .448 32, .147 1. .00 40, .05 6

ATOM 3990 CB ALA c 88 34 .356 61 .250 33 .005 1 .00 40 .30 6

ATOM 3991 C ALA c 88 35 .939 63 .169 32 .771 1 .00 41 .63 6

ATOM 3992 O ALA c 88 36 .912 62 .545 33 .195 1, .00 41, .71 8

ATOM 3993 N TYR c 89 35 .852 64 .492 32 .799 1, .00 42 .71 7

ATOM 3994 CA TYR c 89 36 .904 65 .350 33 .330 1 .00 41 .60 6

ATOM 3995 CB TYR c 89 36 .368 66 .775 33 .459 1 .00 43 .41 6

ATOM 3996 CG TYR c 89 35 .976 67 .422 32 .149 1 .00 48 .68 6

ATOM 3997 CDl TYR c 89 35 .321 68 .653 32 .129 1 .00 51 .90 6

ATOM 3998 CEl TYR c 89 34 .991 69 .284 30, .920 1, .00 53, .01 6

ATOM 3999 CD2 TYR c 89 36 .290 66 .830 30 .929 1, .00 48, .32 6

ATOM 4000 CE2 TYR c 89 35 .966 67 .449 29 .726 1 .00 52 .45 6

ATOM 4001 CZ TYR c 89 35 .318 68 .678 29, .730 1, .00 53, .45 6

ATOM 4002 OH TYR c 89 35 .017 69 .305 28 .545 1 .00 56 .75 8

ATOM 4003 C TYR c 89 37 .527 64 .914 34 .657 1 .00 40 .68 6

ATOM 4004 0 TYR c 89 38 .727 65 .075 34 .863 1 .00 39 .21 8

ATOM 4005 N ASN c 90 36 .725 64 .364 35 .562 1 .00 39 .53 7

ATOM 4006 CA ASN c 90 37 .265 63 .952 36 .848 1 .00 39 .15 6

ATOM 4007 CB ASN c 90 36 .476 64 .603 37 .989 1 .00 38 .99 6

ATOM 4008 CG ASN c 90 ^'34 .995 64 .290 37 .944 1 .00 38 .22 6

ATOM 4009 ODl ASN c 90 34 .355 64 .378 36 .902 1 .00 37 .33 8

ATOM 4010 ND2 ASN c 90 34 .443 63 .939 39 .090 1 .00 39 .59 7

ATOM 4011 C ASN c 90 37 .343 62 .448 37 .033 1 .00 41 .22 6

ATOM 4012 O ASN c 90 37 .354 61 .946 38 .153 1 .00 42 .78 8

ATOM 4013 N ALA c 91 37 .400 61 .733 35 .915 1 .00 42 .37 7

ATOM 4014 CA ALA c 91 37 .528 60 .292 35 .928 1 .00 40 .71 6

ATOM 4015 CB ALA c 91 37 .346 59 .733 34 .521 1 .00 41 .88 6 ATOM 4016 C ALA C 91 38.939 60.033 36.435 1.00 39.96 6

ATOM 4017 O ALA C 91 39. 898 60. 664 36. 007 1. 00 35. 60 8

ATOM 4018 N ILE C 92 39. 040 59. 093 37. 356 1. 00 41. 49 7

ATOM 4019 CA ILE C 92 40. 292 58. ,731 37. .993 1. 00 43. ,20 6

ATOM 4020 CB ILE C 92 40. 020 58, ,594 39. .511 1. 00 47. ,77 6

ATOM 4021 CG2 ILE C 92 39. 923 57. 130 39. 921 1. 00 48. 36 6

ATOM 4022 CGI ILE C 92 41. 093 59. 293 40. ,316 1. 00 50. 98 6

ATOM 4023 CDl ILE C 92 40. ,903 59. ,036 41. .812 1. 00 55. ,36 6

ATOM 4024 C ILE C 92 40. ,861 57. ,416 37. .403 1. ,00 41. .81 6

ATOM 4025 O ILE C 92 41. 973 56. ,992 37. .720 1. 00 40. ,19 8

ATOM 4026 N SER C 93 40. 080 56. ,781 36. .541 1. 00 39. 24 7

ATOM 4027 CA SER C 93 40. ,470 55. ,534 35. .913 1. 00 39. ,09 6

ATOM 4028 CB SER C 93 39, ,892 54. .356 36, .685 1. ,00 39. ,19 6

ATOM 4029 OG SER C 93 38. ,479 54. .310 36. .541 1. 00 39. ,34 8

ATOM 4030 C SER c 93 39. ,839 55. .579 34, .546 1. ,00 37. ,69 6

ATOM 4031 O SER c 93 38. ,987 56. .404 34. .311 1. ,00 39. ,27 8

ATOM 4032 N LYS c 94 40. .251 54. .717 33. .632 1. ,00 37. ,58 7

ATOM 4033 CA LYS c 94 39. ,612 54. .737 32. .330 1. ,00 40, .65 6

ATOM 4034 CB LYS c 94 40. ,560 54. .256 31, .228 1. ,00 41, .66 6

ATOM 4035 CG LYS c 94 41. .383 53, ,024 31, .520 1. ,00 46. .32 6

ATOM 4036 CD LYS c 94 42. .502 52. ,902 30, .485 1. .00 48, .62 6

ATOM 4037 CE LYS c 94 41, .962 53. .091 29, .069 1. ,00 47, .90 6

ATOM 4038 NZ LYS c 94 42, .999 52, .929 28, .024 1. ,00 48, .05 7

ATOM 4039 C LYS c 94 38, .321 53, .926 32 .359 1. .00 40, ,78 6

ATOM 4040 O LYS c 94 38, .102 53. .094 33, .234 1. ,00 42, .52 8

ATOM 4041 N PRO c 95 37, .434 54. .178 31, .404 1. .00 41. ,55 7

ATOM 4042 CD PRO c 95 37, .555 55, .150 30 .312 1. .00 42, .12 6

ATOM 4043 CA PRO c 95 36, .153 53, .479 31, .335 1. .00 41, .34 6

ATOM 4044 CB PRO c 95 35 .439 54, .166 30 .177 1. .00 41, .08 6

ATOM 4045 CG PRO c 95 36, .125 55, .476 30, .058 1. .00 42, .87 6

ATOM 4046 C PRO c 95 36, .256 52, .000 31. .102 1. ,00 40, ,86 6

ATOM 4047 O PRO c 95 36 .941 51 .563 30 .189 1. .00 41 .65 8

ATOM 4048 N GLU c 96 35 .581 51 .228 31 .940 1. .00 40 .55 7

ATOM 4049 CA GLU c 96 35, .560 49, .791 31, .766 1. .00 41, .10 6

ATOM 4050 CB GLU c 96 35 .684 49, .050 33 .104 1. .00 43, .71 6

ATOM 4051 CG GLU c 96 35 .762 47 .521 32 .954 1, .00 49 .85 6

ATOM 4052 CD GLU c 96 35 .912 46 .768 34 .286 1. .00 54 .35 6

ATOM 4053 OEl GLU c 96 36. .282 47, .404 35 .302 1. ,00 58 .62 8

ATOM 4054 OE2 GLU c 96 35. .682 45, .534 34 .316 1, ,00 52 .48 8

ATOM 4055 C GLU c 96 34 .190 49 .553 31 .168 1, ,00 39 .91 6

ATOM 4056 O GLU c 96 33 .200 49 .478 31 .894 1, .00 40 .62 8

ATOM 4057 N VAL c 97 34 .133 49 .483 29 .841 1, .00 35 .73 7

ATOM 4058 CA VAL c 97 32 .876 49. .249 29 .153 1, .00 34 .27 6

ATOM 4059 CB VAL c 97 33 .006 49 .541 27 .660 1, .00 31 .66 6

ATOM 4060 CGI VAL c 97 31 .686 49 .333 26 .968 1, .00 34 .09 6

ATOM 4061 CG2 VAL c 97 33 .437 50 .963 27 .470 1, .00 30 .22 6

ATOM 4062 C VAL c 97 32 .481 47 .801 29 .382 1, .00 34 .55 6

ATOM 4063 O VAL c 97 33 .167 46 .891 28 .949 1 .00 35 .63 8

ATOM 4064 N LEU c 98 31 .362 47 .607 30 .072 1, .00 35 .35 7

ATOM 4065 CA LEU c 98 30 .868 46 .286 30 .433 1, .00 34 .12 6

ATOM 4066 CB LEU c 98 30 .098 46 .377 31 .752 1 .00 33 .63 6

ATOM 4067 CG LEU c 98 30 .741 47 .049 32 .961 1 .00 35 .44 6

ATOM 4068 CDl LEU c 98 29 .694 47 .352 33 .989 1 .00 37 .77 6

ATOM 4069 CD2 LEU c 98 31 .806 46 .166 33 .538 1. .00 34 .23 6

ATOM 4070 C LEU c 98 29 .965 45 .641 29 .404 1 .00 36 .94 6

ATOM 4071 O LEU c 98 29 .640 44 .464 29 .524 1 .00 39 .49 8

ATOM 4072 N THR c 99 29 .567 46 .398 28 .389 1 .00 36 .94 7

ATOM 4073 CA THR c 99 28 .642 45 .881 27 .393 1 .00 36 .72 6

ATOM 4074 CB THR c 99 27 .317 46 .674 27 .450 1 .00 36 .81 6

ATOM 4075 OG1 THR c 99 27 .574 48 .076 27 .259 1 .00 40 .25 8

ATOM 4076 CG2 THR c 99 26 .648 46 .474 28 .792 1 .00 34 .14 6 ATOM 4077 c THR C 99 29.154 45.,895 25.965 1.00 37.,65 6

ATOM 4078 O THR C 99 30. 147 46. ,549 25. 664 1. 00 37. ,93 8

ATOM 4079 N PRO C 100 28. ,497 45. ,134 25. .073 1. ,00 37. .89 7

ATOM 4080 CD PRO C 100 27. ,443 44. .145 25. ,364 1. ,00 40. .71 6

ATOM 4081 CA PRO C 100 28. 874 45. ,065 23. ,667 1. 00 37. ,03 6

ATOM 4082 CB PRO C 100 27. .716 44, .298 23. ,046 1. ,00 37. .46 6

ATOM 4083 CG PRO C 100 27. 402 43. .316 24. ,094 1. 00 38. ,27 6

ATOM 4084 C PRO C 100 28. .963 46. ,476 23. ,139 1. ,00 38. ,41 6

ATOM 4085 O PRO C 100 28. ,082 47. .297 23. ,390 1. ,00 39. .24 8

ATOM 4086 N GLN C 101 30. .026 46. ,772 22. .412 1. ,00 38. .06 7

ATOM 4087 CA GLN C 101 30. .169 48. ,113 21. ,893 1. ,00 .39. ,24 6

ATOM 4088 CB GLN C 101 31. ,639 48. ,479 21. .827 1. ,00 38. ,35 6

ATOM 4089 CG GLN C 101 32. .140 48, .846 23. .195 1. ,00 43, .58 6

ATOM 4090 CD GLN C 101 33. ,633 48. ,822 23. .291 1. ,00 47. ,06 6

ATOM 4091 OEl GLN C 101 34. .315 49, ,497 22. .533 1. ,00 51. ,61 8

ATOM 4092 NΞ2 GLN C 101 34. .160 48, ,041 24. .227 1. ,00 48. .13 7

ATOM 4093 C GLN C 101 29. .471 48, .333 20. .571 1, ,00 38 .37 6

ATOM 4094 O GLN C 101 30. .095 48 .620 19, .554 1. ,00 36, .55 8

ATOM 4095 N LEU C 102 28. .148 48. .198 20. .627 1. ,00 40, .04 7

ATOM 4096 CA LEU C 102 27, .263 48 .373 19, .478 1. .00 40, .82 6

ATOM 4097 CB LEU C 102 26, ,376 47, .143 19, .289 1. ,00 38 .65 6

ATOM 4098 CG LEU C 102 27 .061 45 .791 19 .163 1, .00 40 .16 6

ATOM 4099 CDl LEU C 102 26, ,015 44, .708 18, .994 1. .00 37, .69 6

ATOM 4100 CD2 LEU C 102 27, .991 45, .815 17, .981 1. .00 39, .89 6

ATOM 4101 C LEU c 102 26, .362 49, .583 19, .685 1. .00 40, .48 6

ATOM 4102 O LEU c 102 25, .940 49, .880 20. ,800 1, ,00 39, ,50 8

ATOM 4103 N ALA c 103 26. .072 50, .280 18, ,603 1. .00 40, .58 7

ATOM 4104 CA ALA c 103 25. .203 51, .434 18. .674 1. ,00 42 .17 6

ATOM 4105 CB ALA c 103 25 .879 52 .646 18 .054 1. .00 43 .90 6

ATOM 4106 C ALA c 103 23 .950 51 .087 17, .904 1, .00 43 .55 6

ATOM 4107 O ALA c 103 23 .905 50 .092 17 .189 1 .00 44 .89 8

ATOM 4108 N ARG c 104 22. .930 51, .916 18. .048 1, ,00 45, .38 7

ATOM 4109 CA ARG c 104 21, .674 51, ,689 17. .359 1, ,00 46, .54 6

ATOM 4110 CB ARG c 104 20, .549 51 .665 18, .381 1, .00 46 .10 6

ATOM 4111 CG ARG c 104 19, .292 51, .040 17. .879 1. ,00 47, .91 6

ATOM 4112 CD ARG c 104 19, .457 49, .560 17, .559 1, .00 45 .29 6

ATOM 4113 NE ARG c 104 18, .188 49 .059 17, .035 1, .00 46 .68 7

ATOM 4114 CZ ARG c 104 17 .927 47 .792 16 .761 1 .00 46 .66 6

ATOM 4115 NHl ARG c 104 18, .850 46 .866 16, .954 1. ,00 47 .05 7

ATOM 4116 NH2 ARG c 104 16, .733 47 .452 16, .308 1, ,00 48 .97 7

ATOM 4117 C ARG c 104 21, .491 52, .830 16. .367 1. ,00 46 .82 6

ATOM 4118 O ARG c 104 21, .550 53, .999 16, .738 1, ,00 49 .29 8

ATOM 4119 N VAL c 105 21 .296 52 .501 15 .098 1 .00 47 .65 7

ATOM 4120 CA VAL c 105 21, .138 53, .543 14, .092 1. .00 47 . 99 6

ATOM 4121 CB VAL c 105 22 .200 53 .426 12 .980 1, .00 46 .29 6

ATOM 4122 CGI VAL c 105 22 .080 54 .588 12, .021 1 .00 44 .96 6

ATOM 4123 CG2 VAL c 105 23 .583 53 .386 13 .580 1 .00 42 .95 6

ATOM 4124 C VAL c 105 19 .769 53 .519 13 .444 1 . 00 50 .20 6

ATOM 4125 O VAL c 105 19, .340 52, .497 12, ,904 1. .00 50 .01 8

ATOM 4126 N VAL c 106 19 .097 54 .666 13, .506 1. .00 51 .90 7

ATOM 4127 CA VAL c 106 17 .767 54 .836 12 .933 1, .00 53 .33 6

ATOM 4128 CB VAL c 106 16 .947 55 .840 13 .758 1 .00 51 .93 6

ATOM 4129 CGI VAL c 106 15, .503 55, .825 13, .306 1, .00 49 .94 6

ATOM 4130 CG2 VAL c 106 17, .060 55 .504 15, .222 1, .00 50 .56 6

ATOM 4131 C VAL c 106 17 .899 55 .347 11 .497 1 .00 53 .76 6

ATOM 4132 O VAL c 106 18 .782 56 .151 11 .203 1 .00 52 .33 8

ATOM 4133 N SER c 107 17 .016 54 .889 10 .615 1 .00 54 .08 7

ATOM 4134 CA SER c 107 17, .066 55, .275 9, .208 1, .00 56 .13 6

ATOM 4135 CB SER c 107 15 .835 54 .734 8 .487 1 .00 56 .67 6

ATOM 4136 OG SER c 107 14 .672 54 .943 9 .268 1 .00 59 .41 8

ATOM 4137 C SER c 107 17, .228 56, .762 8, .895 1, .00 56 .30 6 ATOM 4138 O SER C 107 17.678 57.,129 7.,797 1.00 55.,13 8

ATOM 4139 N ASP C 108 16. 879 57. 619 9. ,849 1. 00 56. 72 7

ATOM 4140 CA ASP C 108 16. .999 59, .064 9, .632 1. ,00 58. .46 6

ATOM 4141 CB ASP C 108 15. ,875 59. .807 10. ,353 1. ,00 59. ,64 6

ATOM 4142 CG ASP C 108 15. 998 59. ,735 11. ,856 1. 00 60. 59 6

ATOM 4143 ODl ASP C 108 16. ,432 58. .693 12. ,378 1. ,00 61. ,80 8

ATOM 4144 OD2 ASP C 108 15. ,643 60. ,724 12. .520 1. ,00 63. ,04 8

ATOM 4145 C ASP C 108 18. ,345 59. .648 10, .054 1. ,00 58. ,38 6

ATOM 4146 O ASP C 108 18. ,513 60. .859 10. .068 1. ,00 58. .33 8

ATOM 4147 N GLY C 109 19. .299 58. .785 10, .396 1. ,00 59. ,41 7

ATOM 4148 CA GLY C 109 20, .618 59. ,246 10. .786 1. ,00 58, ,66 6

ATOM 4149 C GLY C 109 20. .802 59. ,467 12. .271 1. ,00 59, .58 6

ATOM 4150 O GLY C 109 21. .868 59. ,926 12. .695 1. ,00 59. .07 8

ATOM 4151 N GLU C 110 19. ,775 59. ,165 13, ,064 1. 00 59. ,04 7

ATOM 4152 CA GLU C 110 19. .871 59. .325 14 .508 1. .00 59. .38 6

ATOM 4153 CB GLU C 110 18. .481 59. .327 15. .141 1, .00 62. .39 6

ATOM 4154 CG GLU C 110 18. ,386 60. .020 16, .513 1, .00 66. .23 6

ATOM 4155 CD GLU C 110 18. .717 61, .520 16, .441 1. .00 70. .42 6

ATOM 4156 OEl GLU C 110 18. .640 62. .107 15, ,333 1. ,00 69. .27 8

ATOM 4157 OE2 GLU c 110 19. .047 62, .117 17, .493 1. ,00 72. ,25 8

ATOM 4158 C GLU c 110 20, .677 58, .141 15 .038 1. ,00 59, .61 6

ATOM 4159 O GLU c 110 20, .467 56 .995 14, .623 1. ,00 60, .95 8

ATOM 4160 N VAL c 111 21, ,600 58, .419 15, ,953 1, ,00 57, ,63 7

ATOM 4161 CA VAL c 111 22 .444 57 .379 16 .535 1, ,00 55, .43 6

ATOM 4162 CB VAL c 111 23 .926 57 .620 16 .200 1, .00 55, .71 6

ATOM 4163 CGI VAL c 111 24, ,783 56. ,511 16. .788 1. ,00 53. ,14 6

ATOM 4164 CG2 VAL c 111 24, .105 57. .706 14 .686 1, .00 56, .04 6

ATOM 4165 C VAL c 111 22, .308 57, .337 18, .048 1. .00 54, .63 6

ATOM 4166 O VAL c 111 22, .328 58 .373 18 .706 1, ,00 53, .67 8

ATOM 4167 N LEU c 112 22, .171 56, .137 18 .596 1. .00 53, .09 7

ATOM 4168 CA LEU c 112 22, .050 55 .992 20 .034 1, ,00 53, .62 6

ATOM 4169 CB LEU c 112 20, .638 55, .548 20, .420 1, ,00 56, .64 6

ATOM 4170 CG LEU c 112 19 .380 56, .011 19 .657 1. .00 60, .85 6

ATOM 4171 CDl LEU c 112 19, .439 57, .490 19, .341 1. .00 62, .41 6

ATOM 4172 CD2 LEU c 112 19. .244 55, .207 18, ,374 1. ,00 62. ,32 6

ATOM 4173 C LEU c 112 23 .053 54 .963 20 .542 1, ,00 53, .28 6

ATOM 4174 O LEU c 112 23 .024 53 .807 20 .134 1, ,00 54 .91 8

ATOM 4175 N TYR c 113 23, .943 55, .389 21, .429 1. ,00 50, .87 7

ATOM 4176 CA TYR c 113 24 .947 54 .502 22 .003 1, ,00 47, .87 6

ATOM 4177 CB TYR c 113 26 .362 54 .924 21 .560 1. ,00 44, .85 6

ATOM 4178 CG TYR c 113 27 .500 54 .099 22 .134 1, .00 40 .84 6

ATOM 4179 CDl TYR c 113 27 .428 52 .716 22 .181 1, ,00 39, .92 6

ATOM 4180 CEl TYR c 113 28 .481 51 .956 22 .679 1, .00 39 .26 6

ATOM 4181 CD2 TYR c 113 28 .663 54 .710 22 .602 1, .00 41 .11 6

ATOM 4182 CE2 TYR c 113 29 .720 53 .962 23 .100 1 .00 40 .68 6

ATOM 4183 CZ TYR c 113 29 .625 52 .583 23 .138 1, .00 41 .46 6

ATOM 4184 OH TYR c 113 30 .667 51 .831 23 .649 1, .00 40, .70 8

ATOM 4185 C TYR c 113 24 .805 54 .611 23 .508 1 .00 48 .03 6

ATOM 4186 O TYR c 113 25 .002 55 .673 24 .089 1 .00 47 .83 8

ATOM 4187 N MET c 114 24 .457 53 .508 24 .146 1, .00 48 .88 7

ATOM 4188 CA MET c 114 24 .283 53 .519 25 .583 1 .00 49 .26 6

ATOM 4189 CB MET c 114 22 .809 53 .375 25 .910 1 .00 53 .64 6

ATOM 4190 CG MET c 114 .22 .494 53 .558 27 .370 1 .00 58 .33 6

ATOM 4191 SD MET c 114 20 .864 52 .927 27 .696 1, .00 67 .34 16

ATOM 4192 CE MET c 114 19 .859 54 .330 27 .098 1 .00 65 .99 6

ATOM 4193 C MET c 114 25 .055 52 .393 26 .244 1 .00 47 .94 6

ATOM 4194 O MET c 114 24 .485 51 .360 26 .579 1 .00 48 .32 8

ATOM 4195 N PRO c 115 26 .364 52 .576 26 .440 1 .00 47 .40 7

ATOM 4196 CD PRO c 115 27 .181 53 .711 25 .976 1 .00 49 .35 6

ATOM 4197 CA PRO c 115 27 .207 51 .556 27 .066 1 .00 48 .05 6

ATOM 4198 CB PRO c 115 28 .591 51 .903 26 .545 1 .00 48 .90 6 ATOM 4199 CG PRO C 115 28.,548 53.398 26.,559 1.00 48.,59 6

ATOM 4200 C PRO C 115 27. 153 51. 636 28. ,585 1. 00 48. 68 6

ATOM 4201 O PRO C 115 26. ,976 52. ,720 29. .142 1. ,00 48. ,78 8

ATOM 4202 N SER C 116 27. 291 50. 493 29. .249 1. 00 47. ,05 7

ATOM 4203 CA SER C 116 27. ,292 50. ,481 30. ,699 1. 00 45. 85 6

ATOM 4204 CB SER c 116 26. 746 49. 178 31. ,248 1. 00 45. ,70 6

ATOM 4205 OG SER c 116 26. 731 49. 228 32. ,667 1. 00 46. ,59 8

ATOM 4206 C SER c 116 28. ,743 50. ,607 31. ,097 1. ,00 47, ,30 6

ATOM 4207 O SER c 116 29. ,568 49. ,794 30. ,695 1. 00 48. ,38 8

ATOM 4208 N ILE c 117 29. ,058 51. ,622 31. .892 1. ,00 45. ,86 7

ATOM 4209 CA ILE c 117 30. ,437 51. ,849 32. .293 1. ,00 41. .61 6

ATOM 4210 CB ILE c 117 30. .926 53. .210 31. .749 1. 00 39. .60 6

ATOM 4211 CG2 ILE c 117 32, ,325 53. .499 32. .230 1. ,00 38, ,47 6

ATOM 4212 CGI ILE c 117 30. .876 53. ,208 30, .225 1. ,00 38. .60 6

ATOM 4213 CDl ILE c 117 31, ,025 54. .563 29. .619 1. ,00 34. .54 6

ATOM 4214 C ILE c 117 30, ,708 51. .830 33. .796 1. ,00 42, .04 6

ATOM 4215 O ILE c 117 29, .948 52. .390 34 .587 1. .00 42, .87 8

ATOM 4216 N ARG c 118 31, .787 51. .158 34. ,182 1. ,00 40, .79 7

ATOM 4217 CA ARG c 118 32 .210 51, .162 35 .568 1. .00 40, .35 6

ATOM 4218 CB ARG c 118 32, .607 49. ,782 36. .060 1. ,00 37, ,23 6

ATOM 4219 CG ARG c 118 33. ,172 49. ,866 37. ,455 1. ,00 36. .55 6

ATOM 4220 CD ARG c 118 33 .277 48, .538 38. .156 1. ,00 39 .03 6

ATOM 4221 NE ARG c 118 33, .874 48. .693 39, .483 1. .00 39. .42 7

ATOM 4222 CZ ARG c 118 33 .882 47 .756 40 .424 1, .00 39 .50 6

ATOM 4223 NHl ARG c 118 33, .326 46, ,574 40, .208 1. ,00 40, .01 7

ATOM 4224 NH2 ARG c 118 34, .434 48, .012 41, .594 1. ,00 40. .75 7

ATOM 4225 C ARG c 118 33 .440 52, .065 35 .545 1. .00 41 .99 6

ATOM 4226 O ARG c 118 34, .322 51. .881 34, .722 1. ,00 43, .88 8

ATOM 4227 N GLN c 119 33, .514 53, ,040 36, .436 1. .00 42, .79 7

ATOM 4228 CA GLN c 119 34, .649 53, .947 36, .408 1. .00 43, .05 6

ATOM 4229 CB GLN c 119 34 .439 54 .914 35 .252 1 .00 41 .88 6

ATOM 4230 CG GLN c 119 35 .502 55, .939 35 .034 1. .00 41 .06 6

ATOM 4231 CD GLN c 119 35 .281 56, .668 33 .732 1. .00 41, .03 6

ATOM 4232 OEl GLN c 119 34 .148 56, .899 33 .331 1, .00 40 .46 8

ATOM 4233 NΞ2 GLN c 119 36 .363 57. .039 33, .066 1. ,00 43, .78 7

ATOM 4234 C GLN c 119 34 .786 54 .685 37 .728 1. .00 43 .66 6

ATOM 4235 O GLN c 119 33 .803 54, .937 38, .397 1, .00 45 .00 8

ATOM 4236 N ARG c 120 36 .008 55, .018 38 .113 1, .00 44 .71 7

ATOM 4237 CA ARG c 120 36 .210 55, .722 39 .369 1, .00 48 .39 6

ATOM 4238 CB ARG c 120 37 .414 55 .169 40 .107 1, .00 51, .11 6

ATOM 4239 CG ARG c 120 37 .325 53 .696 40 .397 1, .00 56 .82 6

ATOM 4240 CD ARG c 120 38 .116 53 .386 41 .641 1 .00 64 .45 6

ATOM 4241 NE ARG c 120 37 .375 53, .650 42 .886 1, .00 68 .42 7

ATOM 4242 CZ ARG c 120 37 .903 54 .231 43 .969 1. .00 68 .95 6

ATOM 4243 NHl ARG c 120 39 .169 54 .631 43 .967 1 .00 66 .80 7

ATOM 4244 NH2 ARG c 120 37 .177 54 .373 45 .076 1, .00 69 .05 7

ATOM 4245 c ARG c 120 36 .388 57 .215 39 .168 1 .00 48 .49 6

ATOM 4246 O ARG c 120 36 .937 57 .660 38 .161 1 .00 48 .13 8

ATOM 4247 N PHE c 121 35 .916 57 .992 40 .133 1 .00 47 .70 7

ATOM 4248 CA PHE c 121 36 .013 59 .437 40 .035 1 .00 47 .31 6

ATOM 4249 CB PHE c 121 34 .649 60 . .045 39 .719 1, .00 43 .68 6

ATOM 4250 CG PHE c 121 34 .022 59 .489 38 .504 1 .00 43 .63 6

ATOM 4251 CDl PHE c 121 -33 .365 58 .275 38 .549 1 .00 42 .29 6

ATOM 4252 CD2 PHE c 121 34 .104 60 .165 37 .301 1 .00 44 .87 6

ATOM 4253 CEl PHE c 121 32 .793 57 .741 37 .410 1 .00 44 .63 6

ATOM 4254 CE2 PHE c 121 33 .539 59 .643 36 .160 1 .00 45 .50 6

ATOM 4255 CZ PHE c 121 32 .878 58 .425 36 .213 1 .00 45 .14 6

ATOM 4256 C PHE c 121 36 .535 60 .098 41 .280 1 .00 46 .67 6

ATOM 4257 O PHE c 121 36 .528 59 .525 42 .359 1 .00 47 .10 8

ATOM 4258 N SER c 122 36 .984 61 .328 41 .098 1 .00 47 .71 7

ATOM 4259 CA SER c 122 37 .469 62 .150 42 .187 1 .00 49 .70 6 so oo so oo t so so cx) so so t so ι_o so co co so ∞ ι so so so so so αo t so so co o α) r-- i£i so ιχι ι^

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ATOM 4321 CD GLU C 131 22.,642 64.,580 59.,335 1.00 86.,47 6

ATOM 4322 OEl GLU C 131 22. ,862 65. ,788 59, ,024 1. 00 87. ,43 8

ATOM 4323 OE2 GLU C 131 23. .168 63. .998 60, .320 1. ,00 85. .12 8

ATOM 4324 C GLU C 131 21, .207 63, .185 54, ,715 1. .00 77. .86 6

ATOM 4325 O GLU C 131 20, .460 62. .560 53, ,955 1. 00 76. ,34 8

ATOM 4326 N SER C 132 21, ,771 64. ,355 54. .428 1. ,00 76. ,46 7

ATOM 4327 CA SER C 132 21, .652 64, .995 53. .136 1. ,00 75. .54 6

ATOM 4328 CB SER C 132 21, ,941 66. .495 53. ,290 1. ,00 76, .21 6

ATOM 4329 OG SER C 132 23. ,233 66. .719 53, .841 1. ,00 78, ,77 8

ATOM 4330 C SER C 132 22, .673 64, .318 52, .205 1. .00 74, .37 6

ATOM 4331 O SER C 132 22, .799 64, .675 51, .026 1. .00 74, .56 8

ATOM 4332 N GLY C 133 23 .392 63 .338 52. .764 1. .00 72, .74 7

ATOM 4333 CA GLY C 133 24. .389 62. ,591 52. .019 1. , 00 70, .01 6

ATOM 4334 C GLY c 133 25. .435 63. .449 51. .337 1. ,00 68, .98 6

ATOM 4335 O GLY c 133 25 .636 64 .615 51, .686 1. .00 69 .00 8

ATOM 4336 N ALA c 134 26 .107 62, .859 50, .355 1. ,00 66, .70 7

ATOM 4337 CA ALA c 134 27, .131 63, .563 49, .609 1, ,00 64, .10 6

ATOM 4338 CB ALA c 134 28, .394 62, .723 49, .531 1. .00 63, ,57 6

ATOM 4339 C ALA c 134 26, .641 63, .899 48, .212 1. .00 62. .41 6

ATOM 4340 O ALA c 134 25 .640 63, .360 47, .737 1, .00 60, .16 8

ATOM 4341 N THR c 135 27, ,347 64, .826 47. .573 1. .00 62. .33 7

ATOM 4342 CA THR c 135 27 .023 65, .237 46, .211 1. .00 62 .11 6

ATOM 4343 CB THR c 135 26, .431 66, .642 46, .166 1. .00 61, .79 6

ATOM 4344 OG1 THR c 135 25 .253 66 .675 46, .980 1. .00 65, .07 8

ATOM 4345 CG2 THR c 135 26. ,057 67, ,007 44. .746 1. ,00 60. .95 6

ATOM 4346 C THR c 135 28 .292 65 .181 45, .375 1. .00 60, .85 6

ATOM 4347 O THR c 135 29 .181 66 .040 45, .473 1, .00 61 .27 8

ATOM 4348 N CYS c 136 28, .368 64, .128 44, .574 1. ,00 58, .77 7

ATOM 4349 CA CYS c 136 29, .499 63, .891 43. ,712 1, .00 56. .58 6

ATOM 4350 C CYS c 136 29. .140 64, ,393 42. ,325 1. .00 56. .26 6

ATOM 4351 O CYS c 136 28, .197 63, .907 41, .710 1. .00 56, .21 8

ATOM 4352 CB CYS c 136 29 .794 62 .396 43, .698 1, .00 54 .70 6

ATOM 4353 SG CYS c 136 31, .010 61 .882 42, .454 1. .00 52, .66 16

ATOM 4354 N ARG c 137 29, .874 65, .386 41, .843 1, .00 55, .40 7

ATOM 4355 CA ARG c 137 29, .605 65, .938 40. ,520 1. .00 55, .61 6

ATOM 4356 CB ARG c 137 29 .698 67 .466 40, ,537 1, .00 56, .53 6

ATOM 4357 CG ARG c 137 28, .713 68, .135 41, ,462 1. .00 61. .72 6

ATOM 4358 CD ARG c 137 29 .231 69 .491 41 .947 1, .00 65 .19 6

ATOM 4359 NE ARG c 137 28 .632 69, .871 43, .236 1, .00 69 .78 7

ATOM 4360 CZ ARG c 137 27 .352 70 .221 43 .412 1, .00 71, .88 6

ATOM 4361 NHl ARG c 137 26, .504 70, .256 42, ,384 1, .00 74, .24 7

ATOM 4362 NH2 ARG c 137 26, .908 70, .522 44. .626 1. .00 70, .49 7

ATOM 4363 C ARG c 137 30, .604 65, .392 39. .522 1, .00 55, .23 6

ATOM 4364 O ARG c 137 31 .807 65 .381 39 .773 1 .00 57 .26 8

ATOM 4365 N ILE c 138 30 .095 64 .948 38, .385 1 .00 52 .01 7

ATOM 4366 CA ILE c 138 30, .922 64, .398 37, .333 1, .00 50, .01 6

ATOM 4367 CB ILE c 138 30 .529 62 .928 37 .061 1, .00 49, .70 6

ATOM 4368 CG2 ILE c 138 31 .361 62 .360 35, .933 1, .00 47 .04 6

ATOM 4369 CGI ILE c 138 30. .703 62, .090 38, .327 1, .00 48, .47 6

ATOM 4370 CDl ILE c 138 30 .080 60 .706 38, .225 1 .00 46 .09 6

ATOM 4371 C ILE c 138 30. .693 65, .222 36, .070 1 .00 48 .82 6

ATOM 4372 0 ILE c 138 29 .571 65 .322 35 .597 1 .00 46 .40 8

ATOM 4373 N LYS c 139 ^■31, .752 65 .814 35 .529 1 .00. 49 .18 7

ATOM 4374 CA LYS c 139 31 .634 66 .614 34, .309 1, .00 52. .75 6

ATOM 4375 CB LYS c 139 32 .364 67 .950 34, .464 1 .00 54 .78 6

ATOM 4376 CG LYS c 139 31 .952 68 .737 35 .697 1 .00 59 .35 6

ATOM 4377 CD LYS c 139 32 .477 70 .168 35 .669 1 .00 60 .96 6

ATOM 4378 CE LYS c 139 31 .780 71, .019 34, .594 1 .00 62 .06 6

ATOM 4379 NZ LYS c 139 32 .316 72 .419 34 .559 1 .00 59 .27 7

ATOM 4380 C LYS c 139 32 .218 65 .886 33, .106 1 .00 52 .07 6

ATOM 4381 O LYS c 139 33 .364 65 .446 33 .143 1 .00 52 .64 8 ATOM 4382 N ILE C 140 31.,441 65.,761 32.,036 1.,00 51.,29 7

ATOM 4383 CA ILE C 140 31. 938 65. 091 30. ,842 1. 00 50. 15 6

ATOM 4384 CB ILE C 140 31. .404 63. ,613 30. ,769 1. .00 51. ,22 6

ATOM 4385 CG2 ILE C 140 31. 536 62. 955 32. ,134 1. 00 52. 05 6

ATOM 4386 CGI ILE C 140 29. 930 63. 555 30. ,393 1. 00 49. ,11 6

ATOM 4387 CDl ILE C 140 29. 307 62. ,187 30. ,676 1. ,00 49. ,89 6

ATOM 4388 C ILE C 140 31. 624 65. 861 29. ,560 1. 00 47. 99 6

ATOM 4389 O ILE C 140 30. 515 66. ,323 29. ,365 1. 00 50. 04 8

ATOM 4390 N GLY C 141 32. ,620 66. ,025 28. ,701 1. ,00 46. ,57 7

ATOM 4391 CA GLY C 141 32. ,414 66. .732 27. .447 1. ,00 46. ,87 6

ATOM 4392 C GLY C 141 33. ,453 66. ,323 26. ,416 1. ,00 46. ,66 6

ATOM 4393 O GLY C 141 34. ,359 65. ,565 26. ,739 1. ,00 46. ,42 8

ATOM 4394 N SER C 142 33. .329 66. .804 25. ,180 1. ,00 45. ,19 7

ATOM 4395 CA SER C 142 34. .303 66, .474 24, .140 1. ,00 41. ,98 6

ATOM 4396 CB SER C 142 33. .974 67. ,165 22. .828 1. ,00 40, ,96 6

ATOM 4397 OG SER C 142 35. .062 67. .057 21, .943 1. .00 34. .78 8

ATOM 4398 C SER C 142 35, .698 66. ,885 24, ,551 1. .00 43. .33 6

ATOM 4399 O SER C 142 35, .915 67. .956 25, .115 1. ,00 45. ,01 8

ATOM 4400 N TRP C 143 36. .655 66. ,028 24, ,256 1. 00 43. .12 7

ATOM 4401 CA TRP C 143 38. .025 66. .300 24, .622 1. .00 42. ,98 6

ATOM 4402 CB TRP c 143 38. .768 64. ,982 24. .819 1. .00 41, ,57 6

ATOM 4403 CG TRP c 143 40, .125 65, ,141 25, .446 1. .00 39. .54 6

ATOM 4404 CD2 TRP c 143 40. .394 65. ,420 26, .820 1. .00 36, .50 6

ATOM 4405 CE2 TRP c 143 41, .795 65, ,481 26, .967 1. .00 35. .30 6

ATOM 4406 CE3 TRP c 143 39, .584 65, .625 27, .943 1, .00 36, .55 6

ATOM 4407 CDl TRP c 143 41, .345 65. ,048 24. .829 1. .00 38. ,96 6

ATOM 4408 NEl TRP c 143 42, .353 65, .251 25, .738 1. .00 35, .00 7

ATOM 4409 CZ2 TRP c 143 42, .400 65. ,736 28. ,192 1. ,00 34. .47 6

ATOM 4410 CZ3 TRP c 143 40, .185 65, .878 29 .153 1. .00 35, ,28 6

ATOM 4411 CH2 TRP c 143 41, .580 65, ,931 29, .271 1. .00 35. .16 6

ATOM 4412 C TRP c 143 38, .767 67, .159 23, .605 1. .00 43, .69 6

ATOM 4413 O TRP c 143 39, .657 67. .915 23. ,962 1. .00 46, .65 8

ATOM 4414 N THR c 144 38, .402 67. ,065 22. .338 1. .00 42, .21 7

ATOM 4415 CA THR c 144 39, .107 67, .834 21. .333 1. .00 40, .90 6

ATOM 4416 CB THR c 144 39, .839 66. .901 20, .372 1. .00 40, .06 6

ATOM 4417 OG1 THR c 144 38 .907 65 .976 19 .798 1. .00 40 .17 8

ATOM 4418 CG2 THR c 144 40 .916 66, .144 21, .106 1, .00 38, .34 6

ATOM 4419 C THR c 144 38 .252 68 .795 20, .520 1. .00 43, .03 6

ATOM 4420 O THR c 144 38, .786 69, .631 19, .795 1, .00 43, .02 8

ATOM 4421 N HIS c 145 36, .934 68. .687 20. .635 1. .00 42, .41 7

ATOM 4422 CA HIS c 145 36 .065 69 .571 19 .885 1 .00 45 .42 6

ATOM 4423 CB HIS c 145 34, .994 68. .772 19, .144 1, ,00 48, .25 6

ATOM 4424 CG HIS c 145 35 .533 67 .873 18 .071 1, .00 49 .32 6

ATOM 4425 CD2 HIS c 145 36 .052 68 .154 16 .853 1 .00 47 .20 6

ATOM 4426 NDl HIS c 145 35 .572 66 .500 18 .197 1 .00 47 .13 7

ATOM 4427 CEl HIS c 145 36 .091 65 .976 17 .103 1 .00 47 .99 6

ATOM 4428 NΞ2 HIS c 145 36 .391 66 .958 16 .272 1 .00 48 .34 7

ATOM 4429 C HIS c 145 35 .394 70 .627 20 .754 1 .00 48 .71 6

ATOM 4430 O HIS c 145 34 .738 70 .325 21 .746 1 .00 47 . 60 8

ATOM 4431 N HIS c 146 35 .562 71 .883 20 .363 1 .00 52 .53 7

ATOM 4432 CA HIS c 146 34 .972 72 .993 21 .094 1 .00 53 .12 6

ATOM 4433 CB HIS c 146 35 .777 74 .261 20 .840 1 .00 50 .98 6

ATOM 4434 CG HIS c 146 ^•35 .931 74 .586 19 .390 1 .00 48 .89 6

ATOM 4435 CD2 HIS c 146 35 .013 74 .755 18 .409 1 .00 47 .83 6

ATOM 4436 NDl HIS c 146 37 .161 74 .776 18 .801 1 .00 48 .82 7

ATOM 4437 CEl HIS c 146 36 .993 75 .049 17 .519 1 .00 48 .32 6

ATOM 4438 NΞ2 HIS c 146 35 .699 75 .043 17 .257 1 .00 46 .12 7

ATOM 4439 C HIS c 146 33 .524 73 .188 20 .664 1 .00 54 .19 6

ATOM 4440 O HIS c 146 33 .047 72 .531 19 .736 1 .00 54 .21 8

ATOM 4441 N SER c 147 32 .847 74 .112 21 .341 1 . 00 56 .30 7

ATOM 4442 CA SER c 147 31 .437 74 .418 21 .115 1 .00 57 .23 6 ATOM 4443 CB SER C 147 31.,055 75.610 21.,978 1.00 57.,36 6

ATOM 4444 OG SER C 147 32. ,017 76. .635 21. .828 1. ,00 59. .18 8

ATOM 4445 C SER C 147 30. .972 74. ,660 19. .682 1. .00 57. .72 6

ATOM 4446 O SER C 147 29. ,790 74. .484 19. .375 1. ,00 57. .25 8

ATOM 4447 N ARG c 148 31. ,885 75. .065 18. .809 1. 00 58, ,23 7

ATOM 4448 CA ARG c 148 31. .517 75. .336 17, .424 1. ,00 60. .12 6

ATOM 4449 CB ARG c 148 32. .555 76, .264 16. .777 1. ,00 63. .75 6

ATOM 4450 CG ARG c 148 32, ,799 77. ,567 17. .549 1. .00 70, .83 6

ATOM 4451 CD ARG c 148 33, ,950 78. .393 16. .946 1. 00 77. ,31 6

ATOM 4452 NE ARG c 148 34, .422 79, .453 17, .852 1. .00 84, .18 7

ATOM 4453 CZ ARG c 148 33, ,696 80. ,506 18, .245 1. .00 86, .23 6

ATOM 4454 NHl ARG c 148 32, .447 80. ,661 17. .818 1. ,00 87. ,64 7

ATOM 4455 NH2 ARG c 148 34. ,213 81. .408 19, .072 1. .00 86. .26 7

ATOM 4456 C ARG c 148 31, .390 74, .051 16, .6.01 1. .00 59. .83 6

ATOM 4457 O ARG c 148 30, .786 74, .053 15, .519 1. .00 60. .30 8

ATOM 4458 N GLU c 149 31, .954 72. ,959 17, .121 1. .00 57, .69 7

ATOM 4459 CA GLU c 149 31, .937 71, .677 16, .425 1. ,00 54, .67 6

ATOM 4460 CB GLU c 149 33, .364 71, .132 16, .321 1. ,00 52 .47 6

ATOM 4461 CG GLU c 149 34. .395 72. .228 16, .050 1. ,00 52. .11 6

ATOM 4462 CD GLU c 149 35, ,824 71. ,718 15, .896 1, .00 50, .20 6

ATOM 4463 OEl GLU c 149 36, ,246 70, .852 16, .678 1, .00 49, .43 8

ATOM 4464 OE2 GLU c 149 36 .537 72, .203 15 .004 1, .00 47, .62 8

ATOM 4465 C GLU c 149 31, .043 70, .698 17, .162 1, .00 53, .64 6

ATOM 4466 O GLU c 149 30, .252 69. ,985 16, .552 1. .00 53, .16 8

ATOM 4467 N ILE c 150 31 .172 70, .667 18 .479 1. .00 52 .16 7

ATOM 4468 CA ILE c 150 30, .353 69, .795 19, .289 1. .00 51, .98 6

ATOM 4469 CB ILE c 150 31, .157 68, .612 19, .883 1, .00 53, .49 6

ATOM 4470 CG2 ILE c 150 30, .361 67, .954 21. .019 1. .00 52, .00 6

ATOM 4471 CGI ILE c 150 31 .450 67 .571 18 .800 1 .00 53 .48 6

ATOM 4472 CDl ILE c 150 32, .235 66, .383 19, .299 1, .00 50, .44 6

ATOM 4473 C ILE c 150 29 .750 70, .565 20 .446 1, .00 53 .26 6

ATOM 4474 O ILE c 150 30 .410 71, .389 21 .095 1. .00 51 .01 8

ATOM 4475 N SER c 151 28. .479 70. .280 20, .694 1, .00 54, .99 7

ATOM 4476 CA SER c 151 27 .749 70. .887 21 .797 1, .00 56 .94 6

ATOM 4477 CB SER c 151 26. .693 71, .873 21, .280 1, .00 54 .85 6

ATOM 4478 OG SER c 151 25 .665 71, .221 20 .557 1, .00 55. .92 8

ATOM 4479 C SER c 151 27 .084 69 .717 22 .516 1, .00 59 .00 6

ATOM 4480 O SER c 151 26 .536 68 .820 21 .871 1 .00 60 .03 8

ATOM 4481 N VAL c 152 27 .172 69, .705 23 .844 1, .00 60 .32 7

ATOM 4482 CA VAL c 152 26. .569 68, .651 24 .655 1, .00 61. .16 6

ATOM 4483 CB VAL c 152 27 .564 68 .096 25 .694 1, .00 60 .14 6

ATOM 4484 CGI VAL c 152 28, .858 67. .723 25, .009 1, .00 61. .98 6

ATOM 4485 CG2 VAL c 152 27 .817 69, .110 26, .775 1, .00 61. .23 6

ATOM 4486 C VAL c 152 25 .373 69, .237 25 .391 1 .00 62 .82 6

ATOM 4487 O VAL c 152 25 .379 70, .409 25 .758 1 .00 63 .73 8

ATOM 4488 N ASP c 153 24 .349 68, .425 25 .614 1, .00 65 .81 7

ATOM 4489 CA ASP c 153 23 .147 68, .887 26, .293 1, .00 67 .23 6

ATOM 4490 CB ASP c 153 22 .150 69, .377 25 .249 1 .00 69 .19 6

ATOM 4491 CG ASP c 153 22 .748 70, .425 24 .320 1 .00 72 .38 6

ATOM 4492 ODl ASP c 153 22 .786 71 .614 24 .718 1 .00 72 .90 8

ATOM 4493 OD2 ASP c 153 23 .193 70, .060 23 .201 1 .00 75 .01 8

ATOM 4494 C ASP c 153 22 .505 67 .776 27 .120 1 .00 69 .10 6

ATOM 4495 O ASP c 153 22 .504 66 .612 26 .717 1 .00 68 .47 8

ATOM 4496 N PRO c 154 21 .970 68, .115 28, .304 1, .00 70 .49 7

ATOM 4497 CD PRO c 154 22 .282 69 .309 29 .094 1 .00 69 .97 6

ATOM 4498 CA PRO c 154 21 .325 67, .098 29 .147 1, .00 73 .18 6

ATOM 4499 CB PRO c 154 21 .148 67 .814 30 .477 1 .00 70 .84 6

ATOM 4500 CG PRO c 154 22 .300 68 .745 30 .493 1 .00 71 .35 6

ATOM 4501 C PRO c 154 19 .985 66 .669 28 .522 1 .00 77 .25 6

ATOM 4502 O PRO c 154 .19 .591 67 .183 27 .462 1 .00 77 .76 8

ATOM 4503 N THR c 155 19 .279 65 .744 29 .175 1 .00 80 .57 7 ATOM 4504 CA THR C 155 18.,010 65..253 28.,633 1..00 83.,84 6

ATOM 4505 CB THR C 155 18. ,244 63. ,932 27. ,837 1. ,00 83. ,53 6

ATOM 4506 OG1 THR C 155 18, .609 62, .882 28. ,744 1, .00 83, .26 8

ATOM 4507 CG2 THR C 155 19. ,361 64. .105 26. .823 1. ,00 83. ,08 6

ATOM 4508 C THR C 155 16. .897 65. .001 29. .678 1. .00 87. ,74 6

ATOM 4509 O THR C 155 16. ,826 65. ,677 30. .715 1. ,00 87. .94 8

ATOM 4510 N THR C 156 16. ,042 64. .012 29. ,370 1. .00 91. .72 7

ATOM 4511 CA THR C 156 14. ,882 63. .577 30. .180 1. ,00 93. .73 6

ATOM 4512 CB THR C 156 14. .501 62. ,092 29. .877 1. .00 93. .94 6

ATOM 4513 OG1 THR C 156 14, ,249 61, .933 28. .470 1. ,00 93. .93 8

ATOM 4514 CG2 THR C 156 13. .253 61. .681 30. .696 1. .00 93. .29 6

ATOM 4515 C THR C 156 15, .042 63, .695 31. .693 1, ,00 95. .32- 6

ATOM 4516 O THR C 156 15. .626 62, .817 32. .347 1. .00 95, .61 8

ATOM 4517 N GLU C 157 14. .490 64, .767 32. .246 1, .00 97. .07 7

ATOM 4518 CA GLU C 157 14. .578 65, ,011 33. ,679 1, ,00 98, .94 6

ATOM 4519 CB GLU C 157 14, .487 66 .514 33, .942 1, .00100. .27 6

ATOM 4520 CG GLU C 157 15. .282 67, .359 32, .950 1. .00102, .55 6

ATOM 4521 CD GLU C 157 15, .113 68 .852 33, .214 1, .00104, .54 6

ATOM 4522 OEl GLU C 157 13. .943 69, .322 33. ,312 1, ,00105. ,88 8

ATOM 4523 OΞ2 GLU C 157 16, .150 69 .555 33, .327 1, .00104, .90 8

ATOM 4524 c^' GLU c 157 13. .475 64, .290 34, .465 1, ,00 99. .30 6

ATOM 4525 O GLU c 157 13, .452 64 .337 35, .706 1, .00 99, .77 8

ATOM 4526 N ASN c 158 12, .557 63 .639 33 .751 1 .00 99, .15 7

ATOM 4527 CA ASN c 158 11. .457 62, .919 34, .404 1, .00 98, .32 6

ATOM 4528 CB ASN c 158 10. .382 62 .541 33 .374 1 .00100 .43 6

ATOM 4529 CG ASN c 158 9. .902 63 .736 32, .555 1, .00101, .38 6

ATOM 4530 ODl ASN c 158 9 .423 64 .738 33 .112 1 .00101 .96 8

ATOM 4531 ND2 ASN c 158 10. .026 63, .636 31. .224 1. .00101, .40 7

ATOM 4532 C ASN c 158 11. .991 61, .638 35, .064 1, .00 96, .64 6

ATOM 4533 0 ASN c 158 12. .380 61. .643 36. .239 1. .00 96. ,33 8

ATOM 4534 N SER c 159 11 .992 60 .558 34 .283 1, .00 93 .61 7

ATOM 4535 CA SER c 159 12 .466 59 .237 34 .690 1 .00 90 .35 6

ATOM 4536 CB SER c 159 13 .541 58 .788 33 .690 1, .00 90. .84 6

ATOM 4537 OG SER c 159 14 .367 59 .898 33 .320 1 .00 90 .44 8

ATOM 4538 C SER c 159 13, .005 59, .167 36, .123 1, ,00 88, .15 6

ATOM 4539 O SER c 159 13 .942 59 .894 36 .481 1 .00 88 .99 8

ATOM 4540 N ASP c 160 12, .414 58, .302 36, .945 1. .00 84, .53 7

ATOM 4541 CA ASP c 160 12. .863 58, .152 38, .330 1. .00 80, .47 6

ATOM 4542 CB ASP c 160 12. .232 56, .921 38. .985 1, .00 80, .26 6

ATOM 4543 CG ASP c 160 12, .760 56, .683 40, .398 1, ,00 82. .12 6

ATOM 4544 ODl ASP c 160 12. .658 55, .536 40. ,890 1. ,00 82, .78 8

ATOM 4545 OD2 ASP c 160 13. .277 57, .644 41, .023 1, .00 82, .17 8

ATOM 4546 C ASP c 160 14 .380 57 .978 38 .340 1 .00 77 .39 6

ATOM 4547 O ASP c 160 14. .892 57 .009 37, .768 1 .00 75, .75 8

ATOM 4548 N ASP c 161 15 .080 58 .910 38 .992 1 .00 73 .66 7

ATOM 4549 CA ASP c 161 16, .529 58 .864 39, .072 1, .00 71, .77 6

ATOM . 4550 CB ASP c 161 17 .060 59 .934 40 .028 1 .00 71, .93 6

ATOM 4551 CG ASP c 161 16, .943 61 .330 39, .461 1, .00 72, .28 6

ATOM 4552 ODl ASP c 161 17, .115 61, ,486 38, .230 1, .00 71, .71 8

ATOM 4553 OD2 ASP c 161 16, .695 62 .270 40 .246 1, .00 74 .13 8

ATOM 4554 C ASP c 161 17, .118 57, .515 39, .479 1, .00 70, .97 6

ATOM 4555 O ASP c 161 18 .296 57 .251 39 .222 1 .00 73 .00 8

ATOM ^' 4556 N SER c 162 16 .335 56 .649 40 .105 1 .00 68 .54 7

ATOM 4557 CA SER c 162 16 .899 55 .366 40 .496 1 .00 66 .65 6

ATOM 4558 CB SER c 162 17 .085 55 .308 42 .020 1 .00 66 .09 6

ATOM 4559 OG SER c 162 15 .845 55 .352 42 .698 1 .00 66, .84 8

ATOM 4560 C SER c 162 16 .064 54 .194 40 .019 1 .00 65 .29 6

ATOM 4561 O SER c 162 16 .042 53 .147 40 .646 1, .00 65, .08 8

ATOM 4562 N GLU c 163 15 .393 54 .357 38 .892 1 .00 64 .69 7

ATOM 4563 CA GLU c 163 14, .571 53, .270 38, .398 1, .00 66, .58 6

ATOM 4564 CB GLU c 163 13 .543 53 .784 37 .372 1. .00 68, .86 6 CD en en ^ 4^ eo oo IV) IV) O en o en o en o en o en en to to to to to to to to to to to to to to to to to te to l3 t9 ^ ^ θ θ ή ^ ^ B B e ή B ι3 β ^ ^ e ^ fl ιa ^ ι3 ή ^ e ^ ^ ι3 ι H3 ή ^ ι3 ^ ι3 ^ >9 ^ ^ ^ fl fl ^ ή ^ ^ ή ^ ^ ^ ^ ή ^ ^ ^ B ι3 ^ O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O Q O O O Q O O Q O Q O Q O Q Q Q

m m oi oi m m m m oi m m m m m σi σi ^ σi oi σi m oi m m m ui ii ui ui iΛ ifl Oi w αi ui iJ ui in iΛ Ui iΛ Ui ui w ) _j _ M W _ μ μ μ μ μ μ μ p μ μ o o o o o o o o o o a io ^ ι_) io « ιi) «3 it) «) (» m (D Q Co ra ι» co co -θ Ni --i vθ i i i i i i si m (iι m oι oι uι _>l^ W M μ^j o so cΛ -J cn Lπ ^ ω to μ-> o ∞ -j σ Ln ιj_^ ω t μ^j o so ∞

Ω O Ω Ω a O Ω O Ω Ω Ω Ω Ω Ω Ω Ω a O a O Ω Ω a O Ω O Ω Ω a Ω Ω Ω Ω Ω Ω Ω O Ω a O Ω O Ω Ω Ω Ω Ω Ω Ω Ω a O Ω O O Ω Ω Ω IS ΪI N M tl H d ta tfl ^ Ω ft⁾ N M W O d n SDs K N B α O Q tl) t? H D Ω t t p p co μ-s U P ts) H CO CO h-ⁱ P-> co μ-*

[o m w to [n ιa ι3 ^ β ι3 ^ ιa ^ ^ ^ 6 ^ n θ n θ i Ω Q θ n ( to [o tn to iι) ^lt] iι) itl fl 't) >cl 'ι) ^tι) ta 'd ^ ^ ^ ^ ι3 ι3 ι3 ι3 H3 ^3 ι-3 ι-3 Ω Ω Ω Ω Ω Ω M M M M M κ. ^!-^{, !} _ _<_ κ_ κ_ ^!-^l κ_ κ_ κ. κ_ κ_ lr¹ lr^, tr^l l^ . K; ■ μ • ■ V tr¹ f tr¹ tr¹ F

^ p ϋ p » d ^ d ^ p ^ pd p |_d ^ a a a a ^ a ^ _S d pd pd ^ pd M M H M M M H α α α

Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω

t ts) _s) _s) ts) M _ P P P P H - t t ts) to M H H p μ^ μ-^> p p t t to to tO -O p p io tO -O to to to μ ,- r- p p p p p p μ p p p p μ-^ι μ-> μ^ μ-> μ-* μ^j μ^j μ-^s ω ι- uι ⁾ _o ω ιo j co (xn£> w θ o p p o «ι ifl ijι uι oi si -j m oo sson ro-i o .— i uμ-^ji κtoι _σ—ι no nono Sson (o.j_ ϊμ—^ji (_ ro—t Iμ—-^v o >JnO so oo so co tf5. Ln Ln cn cn i -J oo -j cn _p=. Lπ to ts_> to .ι___. c ι --J l c_o - i Lπ cn μ-¹ Lo c 3 o NJ cn cn ι)^ __π Lπ o t ^ Fi^ LJ o^ Nj ⁾ o so o σ o^

OT ι)-» ω Lπ LJ co D ω o cn o co ι^ L ιf-. Lπ ιi^ - i ιf__. ι^ X) ω σ^ μJ J ιP_. ι^ w o Ln Lυ M c oJ θ .p- σ. ι co θ π Lπ ^ L co o .l^ c_ . -j μ-> o cn o .-j ω so oo <_ -J ∞ ω o ι -θ Ln σι i_θ ιi-» ιi-> o μ^j co σ υ ^ to σ. tNj !> o ω Lπ o^ Lo -j Ln L^ o c cσ π >fc. oo GJ θ C_rt ω o ₁^ μ-^l μ-¹ o μ-^s ω . > SD Lπ σ-> -t^ o Lπ -o o o o L^ μ^j ι o^ ω _n --J h-' c_o ιl^ ιJ so o π L ₁^ μ-ι ι-> Ln Lπ ι^ Lo m _-¹ Lπ L ιt-. Lιj μJ J _tp__, ,(__» j____. rf..., rf____. μf..,. j__=_. ,_[____. μ_^. μ__. ...... ^.s, J L O Ul μ^j μ^j μ^ ^j μ^j μ^ ^j μ-ⁱ μⁱ μ^j μ^j μ-^ι μ-^ι μ-' μ^j μ^j .-^l H μ-> μ^j μ-' i-^l μ^ H μ^j μ^j μ-' μ-^s μⁱ R -> μ-> μ-> p^ι μ-¹ μ-^ι μ-^> μ-^> μ-^> μ-^ι H μ-^ι μ^j μ-> μ-^ι ' μ-^ι -' μ-' μ-^ι μ^j μ-¹ μ-^{1 μ}-¹ o o o o o o o o o σ o o o o o σ o ooooσooooooσoooooooooooooooooooooooooooooo o o o o o o o o o o o n o o o o o ooooσo ocDo ooooo ooo oσ oσoooooooo ooσoo σo ooo oo o m Lπ _n n c_π o -~j ∞ O θr\ μ ω ω o m σι W o ω

N3 tO O ιl-. ω iD ω uι m tS (!i oι ^ θ3 σι _o σι m oi (Λ m σι (_ι σι ~j ι_ m l CD m oι _n -Λ si (i) m ffl m oi si CB m σι (_ι m m tΛ m

ATOM 4626 O SER C 169 22.803 49.148 48.,699 1.00 60.78 8

ATOM 4627 N ARG c 170 25. 052 49. ,215 48. ,621 1. 00 59. 44 7

ATOM 4628 CA ARG c 170 25. 174 49. ,662 49. ,998 1. 00 58. 39 6

ATOM 4629 CB ARG c 170 26. 636 49. ,602 50. ,438 1. 00 59. 12 6

ATOM 4630 CG ARG c 170 26. 999 48. ,350 51. ,195 1. 00 61. 61 6

ATOM 4631 CD ARG c 170 28. 466 47, .972 51. .024 1. 00 64. ,86 6

ATOM 4632 NE ARG c 170 29. ,418 49. .012 51. .424 1. 00 66. 40 7

ATOM 4633 CZ ARG c 170 30. 317 49, .556 50. .597 1. 00 68. ,28 6

ATOM 4634 NHl ARG c 170 30. 384 49. .165 49. .326 1. 00 66. 23 7

ATOM 4635 NH2 ARG c 170 31. ,166 50, .480 51, ,039 1. ,00 68. ,62 7

ATOM 4636 C ARG c 170 24. ,668 51, .102 50. ,109 1. 00 59. ,25 6

ATOM 4637 O ARG c 170 24. ,416 51. ,609 51. ,215 1. 00 59. . 99 8

ATOM 4638 N PHE c 171 24. .498 51. .759 48, .968 1. ,00 57. .06 7

ATOM 4639 CA PHE c 171 24. 063 53. ,146 48, .982 1. 00 56. 45 6

ATOM 4640 CB PHE c 171 25. ,131 54, .016 48. .324 1. ,00 55. ,23 6

ATOM 4641 CG PHE c 171 26. .521 53, .719 48, ,814 1. .00 54. .51 6

ATOM 4642 CDl PHE c 171 27. .189 52, ,568 48, .400 1. ,00 55. .98 6

ATOM 4643 CD2 PHE c 171 27. .145 54, ,559 49, .724 1. ,00 53, .29 6

ATOM 4644 CEl PHE c 171 28, .463 52. .257 48, .890 1. ,00 55. ,09 6

ATOM 4645 CE2 PHE c 171 28, ,412 54, .258 50, .218 1. ,00 54. ,24 6

ATOM 4646 CZ PHE c 171 29. .074 53, .102 49, .799 1. ,00 54. ,89 6

ATOM 4647 C PHE c 171 22. ,732 53, .346 48, .311 1. .00 55. .77 6

ATOM 4648 O PHE c 171 22. ,164 52. ,406 47, .761 1. .00 55. .57 8

ATOM 4649 N GLU c 172 22, .228 54, .569 48, .376 1, ,00 55. ,26 7

ATOM 4650 CA GLU c 172 20, .947 54, .877 47, .760 1. ,00 58. .65 6

ATOM 4651 CB GLU c 172 19, .806 54, .769 48 .789 1. .00 60. ,96 6

ATOM 4652 CG GLU c 172 19, .891 55, .739 49, .981 1. .00 64, .19 6

ATOM 4653 CD GLU c 172 18. ,753 55. .551 50. .992 1. ,00 64. ,82 6

ATOM 4654 OEl GLU c 172 17, ,626 55. .236 50, .557 1. .00 65, ,38 8

ATOM 4655 OE2 GLU c 172 18, .976 55 .734 52 .216 1. .00 64, .87 8

ATOM 4656 C GLU c 172 21, .014 56, .279 47 .162 1. ,00 59, .71 6

ATOM 4657 O GLU c 172 21, .815 57, .116 47, .600 1, ,00 60, .04 8

ATOM 4658 N ILE c 173 20. .186 56, .530 46, .154 1. .00 58. .96 7

ATOM 4659 CA ILE c 173 20 .182 57, .827 45 .494 1. .00 59. .79 6

ATOM 4660 CB ILE c 173 20, ,016 57, .687 43, .970 1. .00 60. .17 6

ATOM 4661 CG2 ILE c 173 19 .918 59, .071 43 .334 1. .00 57, .73 6

ATOM 4662 CGI ILE c 173 21 .191 56 .896 43 .384 1, .00 59, .23 6

ATOM 4663 CDl ILE c 173 21, .053 56, .663 41 .902 1, .00 58, .26 6

ATOM 4664 C ILE c 173 19, .088 58, .756 45 .977 1, .00 59, .99 6

ATOM 4665 O ILE c 173 17 .912 58 .391 46 .021 1. .00 57 .81 8

ATOM 4666 N LEU c 174 19 .480 59 .972 46 .321 1 .00 60 .93 7

ATOM 4667 CA LEU c 174 18, .510 60, .943 46, .782 1. ,00 62. ,65 6

ATOM 4668 CB LEU c 174 19 .164 61 .916 47 .756 1 .00 62 .58 6

ATOM 4669 CG LEU c 174 19 .967 61 .213 48 .856 1, .00 63 .64 6

ATOM 4670 CDl LEU c 174 20 .647 62 .264 49 .723 1 .00 63 .25 6

ATOM 4671 CD2 LEU c 174 19, .054 60, .303 49 .684 1, .00 61, .62 6

ATOM 4672 C LEU c 174 17 .985 61, .680 45 .564 1, .00 64, .25 6

ATOM 4673 O LEU c 174 16 .781 61 .734 45 .329 1, .00 65 .71 8

ATOM 4674 N ASP c 175 18 .893 62 .223 44 .768 1 .00 65, .23 7

ATOM 4675 CA ASP c 175 18 .485 62 .951 43 .576 1 .00 66 .02 6

ATOM 4676 CB ASP c 175 17 .949 64 .334 43 .991 1 .00 67 .24 6

ATOM 4677 CG ASP c 175 17 .419 65 .160 42 .812 1 .00 68 .54 6

ATOM 4678 ODl ASP c 175 16 .598 64 .650 42 .011 1 .00 69 .53 8

ATOM 4679 OD2 ASP c 175 17 .812 66 .338 42 .695 1 .00 66 .59 8

ATOM 4680 C ASP c 175 19 .651 63 .084 42 .593 1 .00 66 .29 6

ATOM 4681 O ASP c 175 20 .829 63 .031 42 .980 1 .00 66 .20 8

ATOM 4682 N VAL c 176 19 .312 63 .237 41 .318 1 .00 66 .07 7

ATOM 4683 CA VAL c 176 20 .308 63 .391 40 .267 1 .00 65 .83 6

ATOM 4684 CB VAL c 176 20 .426 62 .109 39 .401 1 .00 66 .59 6

ATOM 4685 CGI VAL c 176 21 .382 62 .345 38 .232 1 .00 64 .35 6

ATOM 4686 CG2 VAL c 176 20 .900 60 .943 40 .254 1 .00 63 .70 6 ATOM 4687 C VAL C 176 19.,869 64.,532 39..368 1.,00 67.,12 6

ATOM 4688 O VAL C 176 18. 715 64. ,589 38. ,956 1. 00 67. 64 8

ATOM 4689 N THR C 177 20. ,786 65. ,447 39. ,075 1. 00 68. ,63 7

ATOM 4690 CA THR C 177 20. ,482 66. .573 38. ,200 1. ,00 69. ,48 6

ATOM 4691 CB THR C 177 20. 215 67, ,861 39. ,004 1. 00 69. ,26 6

ATOM 4692 OG1 THR C 177 21. .310 68, .109 39. .894 1. ,00 68. ,92 8

ATOM 4693 CG2 THR C 177 18. ,932 67. .718 39. ,804 1. 00 68. ,40 6

ATOM 4694 C THR C 177 21. ,640 66, .813 37, .245 1. ,00 70. .44 6

ATOM 4695 O THR C 177 22. .802 66, .641 37, .614 1. .00 69, .76 8

ATOM 4696 N GLN C 178 21. ,312 67. .207 36. ,018 1. ,00 71, .94 7

ATOM 4697 CA GLN C 178 22. .320 67. .470 34, .998 1. .00 73. .43 6

ATOM 4698 CB GLN C 178 22. .150 66. ,500 33. .831 1. ,00 76. ,20 6

ATOM 4699 CG GLN C 178 21, .560 65 .148 34 .220 1. .00 80, .00 6

ATOM 4700 CD GLN C 178 21, .896 64, .046 33, .196 1. .00 83, .21 6

ATOM 4701 OEl GLN C 178 21, .745 64 .237 31 .973 1. .00 84, .40 8

ATOM 4702 NE2 GLN C 178 22, .346 62 .889 33 .694 1, ,00 82 .90 7

ATOM 4703 C GLN C 178 22 .149 68 .884 34, .482 1. ,00 72, .16 6

ATOM 4704 O GLN C 178 21, .070 69, .244 34, .044 1, .00 7 .49 8

ATOM 4705 N LYS C 179 23, ,214 69, .675 34, .522 1. .00 71, .74 7

ATOM 4706 CA LYS c 179 23, .166 71 .054 34 .048 1, .00 71 .38 6

ATOM 4707 CB LYS c 179 23, .205 72, .022 35 .233 1, .00 73 .17 6

ATOM 4708 CG LYS c 179 22 .291 71 .610 36 .380 1, .00 78 .41 6

ATOM 4709 CD LYS c 179 22, ,499 72. .459 37, .644 1. .00 79 .07 6

ATOM 4710 CE LYS c 179 21 .814 71 .821 38, .864 1. .00 80, .35 6

ATOM 4711 NZ LYS c 179 22, .363 70, .452 39, .163 1, .00 81. .10 7

ATOM 4712 C LYS c 179 24, .384 71 .301 33, .176 1. .00 70, .13 6

ATOM 4713 O LYS c 179 25 .504 71 .353 33, .681 1, .00 70 .65 8

ATOM 4714 N LYS c 180 24, .180 71. .466 31, .876 1, .00 68, .21 7

ATOM 4715 CA LYS c 180 25, .306 71 .719 30, .978 1. .00 67, .25 6

ATOM 4716 CB LYS c 180 24. ,833 71. ,667 29. .519 1. .00 67. ,12 6

ATOM 4717 CG LYS c 180 24. .008 72 .846 29. ,053 1. .00 63. ,90 6

ATOM 4718 CD LYS c 180 24, .908 73, .920 28, .488 1. .00 63, .70 6

ATOM 4719 CE LYS c 180 25, .645 73, .452 27. ,223 1. .00 63, .89 6

ATOM 4720 NZ LYS c 180 24, .768 73 .295 26, .013 1 .00 62 .80 7

ATOM 4721 C LYS c 180 25, .971 73, .075 31, .266 1. .00 67. .33 6

ATOM 4722 O LYS c 180 25 .552 73 .803 32, .160 1. .00 66 .68 8

ATOM 4723 N ASN c 181 27, ,027 73, .399 30. .528 1. .00 67, .89 7

ATOM 4724 CA ASN c 181 27 .698 74 .674 30. .702 1, .00 67, .78 6

ATOM 4725 CB ASN c 181 27 .967 74 .948 32 .191 1 .00 69 .90 6

ATOM 4726 CG ASN c 181 28, .580 73, .770 32, .916 1, .00 70, .82 6

ATOM 4727 ODl ASN c 181 29 .508 73, .137 32 .422 1 .00 73 .77 8

ATOM 4728 ND2 ASN c 181 28, .071 73 .481 34, ,109 1 .00 70 .00 7

ATOM 4729 C ASN c 181 28 .977 74 .884 29 .901 1 .00 67 .29 6

ATOM 4730 O ASN c 181 29 .937 74 .153 30 .049 1 .00 68 .57 8

ATOM 4731 N SER c 182 28 .978 75 .911 29, .058 1 .00 67 .43 7

ATOM 4732 CA SER c 182 30 .134 76 .248 28, .233 1, .00 66 .28 6

ATOM 4733 CB SER c 182 29 .726 77 .290 27, .186 1, .00 65 .32 6

ATOM 4734 OG SER c 182 30 .731 77 .477 26, .214 1 .00 68 .09 8

ATOM 4735 C SER c 182 31 .230 76 .798 29, .141 1 .00 65 .83 6

ATOM 4736 O SER c 182 30 .941 77 .272 30 .231 1 .00 66 .92 8

ATOM 4737 N VAL c 183 32 .483 76 .731 28 .698 1 .00 65 .76 7

ATOM 4738 CA VAL c 183 33 .613 77 .211 29 .498 1 .00 65 .65 6

ATOM 4739 CB VAL c 183 33 .872 76 .264 30 .696 1 .00 63 .98 6

ATOM 4740 CGI VAL c 183 33 .648 74 .843 30 .277 1 .00 64 .03 6

ATOM 4741 CG2 VAL c 183 35 .292 76 .442 31 .209 1 .00 61 .75 6

ATOM 4742 C VAL c 183 34 .925 77 .375 28 .728 1 .00 65 .88 6

ATOM 4743 O VAL c 183 35 .305 76 .515 27 .944 1 .00 65 .40 8

ATOM 4744 N THR c 184 35 .616 78 .485 28 .957 1 .00 66 .99 7

ATOM 4745 CA THR c 184 36 .892 78 .722 28 .293 1 .00 68 .57 6

ATOM 4746 CB THR c 184 36 .995 80 .168 27 .732 1 .00 67 .80 6

ATOM 4747 OG1 THR c 184 35 .981 80 .369 26 .737 1 .00 66 .40 8 so so co t^ u_ι so so so so so so so oo so co ι so so co ^ oo ι so so co U3 so r-- so so αo LD so r-- so so so so so co ι co r^ cn ^ co a w ι ^ ι C r ^ cM f ^ t m ιn ^ ιn _θ -n cn ^ ^ ιn r ^ ^ D -₄ _ ιH r-- N o α. i o n r^ OT -n Ln i i r t i r i ^ o i_o ^ o-i [ ^ so M in o o H ^ o cM ^ ^ ^ i o> ω S O O O v-I CM CM rO CM CM v-l i-H ιH ro ^ ιn r- t CO i so co o-ι cn c_ri cn o o cTι cn ι--) cn ιn r-- so ιn -n t- ro ro r-l 0 {ii |il (vl ^ st O O {n O O O) M_l llH-J ltl

H so ι r- r- _ ι t ι [ ι ι t c^ t t t^ t-- f-- ι t--- _ r~ r-- t - _ n o3 r-- r-~ o ^ _ - - c-- t t o c- ι t- r~ r- t— r- r-- so so so Lo m sD so m Lθ -n m ιn u-) U α. oooooooooooo o o o σ o coooooooooooocnoooo oooooocDOooooooooooooooo ooσoσooooσoo o σ o σ o o ooooσoooooooσooooσoooooooσσoooooσoσooooσo i-| i-l i-! t-_ v-_ t-_ t-J i-_ tH --_ i-. .-_ H i-J H t-l iH v-t iH i-l tH H t-l i-l iH -t iH vH i-l i-l i-I t-1 H t-1 t-1 t-i t-1 t-1 r-l i-l s-l r-l t-l i-H i-l t-t H H i-l tH i-l iH H t-l H

r^ o^ o co o C σι co cn t-i ιH θ o cn r^ o c ι--i t-ι 3 t co co so ιn oo co sθ θ ^ ι ιn so m cM CM tH

CM CM rO CM CM C l CM CM CM CO I pπ ^ CM CM rO CM rO rO CM CM CM CM CM CM CM CM C CM CM CM C^ so o σι l Ln t-₄ oo ι CΛ αD tH in c c r _ o ι r-~ so oo _ ι ι α cM ^ CM i _n c^ o t σ so t^ so σ tH ιn oΛ .η [ -n ιn ^ <_o _n t-j . _ - ι ^ o co r^ so r-- ^ t o

^•^ ^ι co oo ιn θ -l o M i oo o crι r ^ co so o oo co ^ ι so ^ so _t-i '^ ι so [ o c cn r ∞ σ o κ> t ι > ι/ι ιr) ^ ^ ro c CM x3 Co αo c σ cD Cθ C t so s so ιn ^ so so r~ _o ι m oo _ r~ r^ [ i r~ i_-- r-- c-~ r^ r-- r-- _ i>- t [ co t r^ r-- _ _ -^ M θ ∞ ι ) i ι-l o ^ ^ r^ r- o sD tn o ι co o rsι so oo _ ι cn ι ιn ι ιn ι ^ o M ∞ t^ (^ t-₄ M t ιn s£i sθ H π (_ CM M C θ co σi σ r ι-( _ ^ c o ^ cM r^ c⁾ r ∞ s on ro o ιH cM in o ro cM H θ θ w-ι ^ a ri ^ H m ro σι rθ ιH so ^ oo M ro l ι r--- o M ro Λ oo co r-- cn o σι co r^ c C⁾o ι ι t-i ιH c ro ^ ^ ^ ^ '^ ιn ^ ιn ^ ro ro c H o cM CM C m n iη rt n ^ ^ π r π M n i^η rη ^ j ^ Nⁱ st ij iⁱ ^ st ^ 'i ' ^ N' ^ ^ iⁱ ij ¹ ^ ^ ^

- ι n ιn -n ι Ln ι ιn ιn ι so o sD o ^,_) o ρ-. r-- -_--- ιr-- t~- - o co ∞ α_ι co σι cn cn w-s cn cn o-ι o o o o o o σ o o ι--i H ι--i ι-i t-ι cM CM CM CM CM CM co ω oo co ∞ co ∞ oo oo oo co oo co co cσ oo co co σo oo co oo co co ∞ <o oj θ3 ∞ ιo (D α) co co o3 σi (Λ θι m (_ι αι o\ (rι <Λ θ\ m oι oι σι σι σi (Λ cri (ji (_ι

H t-l t-l HH ιιHH ιιHH ιι--ll tt--l1 H ιH t-l tH t-t tH ιH ιH ι-l rH rH ιH t-l ι-1 ^ ^ -_ ____j ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ _rH _I_| _r-| ^ ^-| ^-| _v-| _I--₎ -_l -l ι-l t--l ^-l -l _r-l ι--l

U CJ U CJ O CJ CJ O U o o u υ ϋ α o u o o o u u o u o cj o u u u c cj o u o cj u o u u u c u cj o cj o u o o o c cj α u u u cj o o i K pj i i ϊ-Ej ϊ-H r"' fH tH £π IH fH cx3 e_ o H csi M ^ ι so r--- co crι θ tH cM m ^ ιn so [ ∞ w-. o H CM ro ^ _n o r-- ∞

^ ^ ιn ιn ι ι ι ι ιn tn ιn ι tø so ω o so so ι_σ so ι > ι^ r- _ r'^ r--- r-- . - ir— r-- r~- c^ tr— t — r— r~- E—- t — c — -~ c-~ c — r— r-- r- - c — r— c— - c-^ r— r— r— r— r-~ c—- E — c — c — c— t — c — r-- ιr-- i- — ir— t — c — r~- c — c—- c— r-- c— - r— !_-— ι_~- c — c~ r-~ r^ co oo oo oo oo cx> cx> oo

90

OO O O OO O O O OOOOOOO O O O O O O O OO O O O O O O O O OO O O O OO O O O O O O O O O OO O O O O O O O O O

_H EH EH lH _H B tH .H EH _H tH tH _H EH -H EH .H B EH EH .H _H .H .H _H tH _H

_ _^ l . .^ .^ _^ _ S[! ι .=__! ι=t; f^ . _ -^ _^ .<; .^ rt_| - -^ . -^

LO o LO O LO O LO O LO T) o CM CM CO CO "fr "fr o I

LO LO CO

to to to to to to to to to to to to to to to to to to to to to to β β ^ β β ^ i^ ^ μS β β β β vβ ^ β β β ^ β β i-S β ⁱ-S β β ^ i-S β i-S i-S i-S -S ^ i-a β ^ β i^ ^ ^ HS β H β β 1-3 -P3 ι-3 ^ β ι-3 ι- β β β ^f- O O O O O O O O O O O O O O O O O O O O O σ O O O O O O O O O O O O O O O O O O O O O O O O Q Q Q Q Q O Q O Q O Q Q O O

O Ω Ω Ω O Ω O Ω O Ω a O Ω a o n o o n n n n O Ω Ω Ω Ω Ω a O Ω O O Ω Ω Ω a O Ω O O Ω Ω Ω Ω a O Ω O Ω O Ω W ^ Ω bd Ω Ω tjd > M M Ω Ω to O O b Jw W t O Ω td ffi N t p to P α Ω w to _-> to p to p to μ c lr^f t-ⁱ t-^, t-¹ t-^, t-^, t-^| lr¹ co co co co co co < < ,^ <; < Ω Ω ΩΩΩ Ω Ω Ω Ω < < <; < < < ^, Ω Ω Ω Ω Ω Ω Ω Ω Ω β β β β ι- ω ra H tS t?d t?d H H H H M H IM H Ifl lIl ^' ^t ^ ι ⁱ tr' _rⁱ t-^| t-^| t^H t-^| t t_ t^H ' >' 5' ' pycocncncocncococolr^, _r^l _₇ ⁴ tr^l t t t_ l_r^, lr^, κ; κ; κ! κ! a α α ; α i ! c_i p w pd ^ι t ir^ι t_ F F t-¹ α d α a a a d ^{^} - ^■f ^{• ■}P ^J P - P ^■- ^■f - ^■iH ^■ ^ ^ >_w ^ j iti ^ it) ! c! c| ___! c! c_|c; c! pd d d

Ω ΩΩ Ω Ω ΩΩΩ ΩΩ Ω Ω O Ω Ω Ω Ω Ω ΩΩ Ω Ω Ω Ω Ω ΩΩ Ω Ω Ω Ω Ω Ω Ω Ω Ω ΩΩ Ω O Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω ΩΩΩΩ n ΩO H μ^j H μ^j μ^j μ^j μ-' μ-' μ-^s μ-' ^j μ-> μ^ μ^{j j} μ-' μ^ μ^j μ^j μ-> μ-' μ^j μ-' μ-^> H^ϊ μ-> R ^j μ-^ι μ^j μ^j μ^j μ^

V_D SO SO S S S0 S0 S 0 S S S > So so s O S SO S S_ S0 SO SO s sO l ⁾ SO s S s s S S0 So LO So ^ SO SO sO l_ ^ so so o s o o co oo oo oo oD Oo -o -j i l -o -o -J c cn cri m c o^ c ai o^ Ln ui Ln Ln Ln

-O tO t -O tO tO M tO tO M -O tO tO M tO -O tO M tO t tO tO tO t tO tO -O M tO M IO M Iso tO t W -O -O l M tO U U L ω Lπ j-. cn __^ Ln Ln ιi^ π ω ιl-> Lji ιl-» π _π -J π _C^ Lπ Lπ Lπ c Xi ω υ Lπ co c5 ιpι. θ ιi^ oo s_o ιl^ π --J Cn oo ιi-. isj ω μ-> OT --J θD θo so Lπ c o Lπ -^ π i£i μ-^l θ3 .-J Ln _NJ Lυ so μ^j θ u-. σ μ^j w so co .-j ._n ∞ μ-> μ-^s υ -o .\} ω

UΛ 0 _a ^ L - l ι⁽^ ∞ .I^ L0 -0 -0, -J .I^ O 0 s0 _ -J l£> .P- --J σ __^ ω o ∞ m oi oi M tn oi ffi m oi ω ιθ - w iD θ P t i^j ω ω u to ω ω ω ω to to o ~ - o cn μ^j ω Ln ~ tfc. cn to μ^ cD Co tθ Lπ cθ LιJ |-s cn .l-. .-> c_n so Lπ ~j ιt-> _^ cn -> ω oo ___n co μ^j oo ιo iΛ w^ _!^ ιi^ Lθ Lπ » o _ι^ ω __ ι μ-' W is3 t>j .^ co tNJ ~o to o ~j o Lι^j |^ o s_» a - ~J π -J c so o ι_ø -sj ~ o -J _o .t-> co n ι^ ιl^ __^ tl^ __^ ._^ .l-» ι(-» -l^ _l^ .l^ .ti ._^ ._^ ιl^ __^ L L lΛ-i L- ω Lθ LO Lπ rt-> ιP. Lo t ιso to to o o o o o cx_ι c>o σo .ι^ w-i Lπ c_n Lπ Lπ Ln oo ~J ~o

_fc o ω σ^ ω M Λ C_n H' Oι l ∞ Lπ i£> ω co _|i o .!^ s Lπ s .l^ ι)^ -^

CD i u μ t p o iO M w ω m m ^ o σi ω i^ o ^ m Λ tJ CD Ui fr N o ^ co m o i^ ^ P o w - t ω w ^ ^ w ui w ω o ^ ω i^ji μ oi fc o μ μ m t^j u iti m o H oi ώ ^ oi tD J U m a o t μ m μ w iii io μ ^ μ u o u o ω t iD iji μ fc ui μ ui u ui oi tΛ CΛ tD CD to μ-> ι-» t-> μ» h-> μ^Λ μ^j μ^j μ μⁱ μ-^{ι Λ} μ^j μ^Λ -^> μ-^> p' μ-^l ι-^s μ^j μ^j _-> ι-^{ι j} μ-' μ^ι μ-' i-> μ^j μ^j μ-> -^ι μⁱ μ-> μ^j μ^j μ-' ^Λ H μ^j μ^j μ^Λ H μ^j μ-> μ-> μ-> μ-^ι μ-' μ-> ι-^> μ oooooooo σooσooooooσooooooo ooooooσoooo oσooooooσooooooσooooσo oo oσo o ooooooooooooooooooooooooooooo oσooooooσooooooσoooooo

Lπ oo

__-. ιl--

ATOM 4870 CB ASN C 200 22.285 64.,232 45.,754 1.00 60.,17 6

ATOM 4871 CG ASN C 200 21. 985 64. ,387 47. 239 1. 00 62. ,50 6

ATOM 4872 ODl ASN c 200 22. ,905 64. .419 48. .070 1. ,00 64, .15 8

ATOM 4873 ND2 ASN c 200 20. 700 64, ,480 47. 583 1. 00 61. ,21 7

ATOM 4874 C ASN c 200 22. ,898 61. ,801 45. .988 1. 00 55; ,97 6

ATOM 4875 O ASN c 200 21. 821 61. ,316 45. 627 1. 00 54. ,75 8

ATOM 4876 N PHE c 201 23. ,739 61. ,181 46. 802 1. 00 53. ,51 7

ATOM 4877 CA PHE c 201 23. ,454 59. ,867 47, ,330 1. ,00 53. .54 6

ATOM 4878 CB PHE c 201 24. 169 58. ,807 46. 503 1. ,00 50, .74 6

ATOM 4879 CG PHE c 201 25. .663 58, .820 46, .677 1. ,00 48, .36 6

ATOM 4880 CDl PHE c 201 26. ,312 57. ,763 47. ,309 1. ,00 45, .72 6

ATOM 4881 CD2 PHE c 201 26. .413 59, .912 46. .252 1. ,00 46. .85 6

ATOM 4882 CEl PHE c 201 27. ,689 57. .794 47. .521 1. ,00 43. .95 6

ATOM 4883 CE2 PHE c 201 27. .782 59. .955 46. .457 1. .00 45. .93 6

ATOM 4884 CZ PHE c 201 28. .425 58. .889 47, ,096 1. .00 44. .09 6

ATOM 4885 C PHE c 201 23. .979 59, .812 48, .749 1. ,00 55, .36 6

ATOM 4886 O PHE c 201 24. .640 60, .739 49. .210 1. ,00 53, .66 8

ATOM 4887 N ARG c 202 23. .698 58, .702 49. .425 1. .00 57, .35 7

ATOM 4888 CA ARG c 202 24. .140 58, .511 50. .792 1. .00 ^•59, .95 6

ATOM 4889 CB ARG c 202 23. .192 59. ,224 51. .744 1. .00 62. ,36 6

ATOM 4890 CG ARG c 202 21, .844 58, .529 51. ,789 1. ,00 64, .26 6

ATOM 4891 CD ARG c 202 20, .831 59, .278 52. .610 1. ,00 67, .26 6

ATOM 4892 NE ARG c 202 19. .555 58, .567 52. ,620 1. ,00 70, .54 7

ATOM 4893 CZ ARG c 202 18, .430 59, .062 53, ,129 1, ,00 69 .46 6

ATOM 4894 NHl ARG c 202 18, .420 60 .270 53, .670 1, ,00 69 .25 7

ATOM 4895 NH2 ARG c 202 17, .315 58, .349 53. .095 1. ,00 69, .56 7

ATOM 4896 C ARG c 202 24, .116 57 .023 51, .119 1, ,00 60 .80 6

ATOM 4897 O ARG c 202 23, .439 56, .231 50, .445 1. .00 60, .45 8

ATOM 4898 N LYS c 203 24. .860 56, .651 52. ,158 1, .00 61, .42 7

ATOM 4899 CA LYS c 203 24. .886 55, .270 52. .603 1, .00 60, .82 6

ATOM 4900 CB LYS c 203 25 .931 55 .088 53 .703 1, .00 59 .66 6

ATOM 4901 CG LYS c 203 25, .988 53 .688 54, .258 1, .00 61 .19 6

ATOM 4902 CD LYS c 203 26 .955 53 .617 55 .404 1. .00 63, .27 6

ATOM 4903 CE LYS c 203 27 .036 52 .209 55 .947 1 .00 66 .98 6

ATOM 4904 NZ LYS c 203 27, .621 51, .250 54. .945 1. .00 68, .80 7

ATOM 4905 C LYS c 203 23 .477 55 .037 53 .157 1. .00 60 .81 6

ATOM 4906 O LYS c 203 22, .878 55, .942 53. .735 1. ,00 60, .52 8

ATOM 4907 N LYS c 204 22, .913 53, .858 52, .944 1. .00 60 .36 7

ATOM 4908 CA LYS c 204 21 .584 53 .606 53, .466 1. .00 60 .22 6

ATOM 4909 CB LYS c 204 21, .017 52, .329 52. .837 1. .00 58, .64 6

ATOM 4910 CG LYS c 204 20 .591 52, .487 51, .381 1, .00 55 .82 6

ATOM 4911 CD LYS c 204 20 .445 51 .140 50, .692 1 .00 51 .95 6

ATOM 4912 CE LYS c 204 19 .975 51 .298 49. .253 1, .00 52 .70 6

ATOM 4913 NZ LYS c 204 19 .967 50 .027 48, .458 1, .00 51 .76 7

ATOM 4914 C LYS c 204 21 .742 53 .460 54, .977 1 .00 62 .01 6

ATOM 4915 0 LYS c 204 22, .711 52 .854 55, .440 1, .00 63 .36 8

ATOM 4916 N GLY c 205 20 .811 54 .022 55 .747 1 .00 62 .55 7

ATOM 4917 CA GLY c 205 20 .898 53 .921 57 .202 1 .00 62 .30 6

ATOM 4918 C GLY c 205 19, .797 53, .078 57, .844 1, .00 61 .75 6

ATOM 4919 OT1 GLY c 205 18 .911 52 .614 57 .093 1 .00 60 .18 8

ATOM 4920 OT2 GLY c 205 19 .811 52, .879 59. .092 1, .00 60 .86 8

ATOM 4921 CB PHE D 1 39 .182 71 .754 1 .648 1 .00 71 .47 6

ATOM 4922 CG PHE D 1 40 .239 71 .385 0. .623 1 .00 73 .60 6

ATOM 4923 CDl PHE D 1 40 .122 70 .241 -0 .169 1 .00 75 .22 6

ATOM 4924 CD2 PHE D 1 41 .397 72 .176 0 .493 1 .00 73 .83 6

ATOM 4925 CEl PHE D 1 41 .141 69 .886 -1. .081 1 .00 75 .00 6

ATOM 4926 CE2 PHE D 1 42 .418 71 .835 -0 .410 1 .00 73 .07 6

ATOM 4927 CZ PHE D 1 42 .289 70 .688 -1. .199 1 .00 74 .63 6

ATOM 4928 C PHE D 1 37 .071 70 .999 2 .658 1 .00 68 .35 6

ATOM 4929 O PHE D 1 37 .607 71 .392 3 .688 1 .00 69 .33 8

ATOM 4930 N PHE D 1 37 .010 72 .284 0 .515 1 .00 69 .08 7 0145

-153

ATOM 4931 CA PHE D 1 37. .756 71. .268 1. .321 1. ,00 69. .54 6

ATOM 4932 N ASP D 2 35. .915 70. .338 2. .678 1. 00 67. .84 7

ATOM 4933 CA ASP Ό 2 35. ,253 70, .061 3. .967 1. 00 66. .03 6

ATOM 4934 CB ASP D 2 33. ,949 69. .266 3. .772 1. 00 66. .47 6

ATOM 4935 CG ASP D 2 34. ,138 68, .032 2. .928 1. 00 68, ,89 6

ATOM 4936 ODl ASP D 2 35. .029 67. .218 3. ,287 1. ,00 68. .16 8

ATOM 4937 OD2 ASP D 2 33, .396 67, .886 1, .912 1. ,00 70, .47 8

ATOM 4938 C ASP D 2 36, .181 69, .310 4, .933 1. ,00 64. .63 6

ATOM 4939 O ASP D 2 37, .378 69, ,165 4, .672 1. ,00 64. .43 8

ATOM 4940 N ARG D 3 35, .639 68, .837 6, .049 1. 00 62. ,26 7

ATOM 4941 CA ARG D 3 36, .461 68, .128 7, ,029 1. ,00 60. .44 6

ATOM 4942 CB ARG D 3 35. ,748 68, ,078 8. ,388 1. 00 60. ,90 6

ATOM 4943 CG ARG D 3 36 .068 69, .254 9, .302 1. .00 60, .80 6

ATOM 4944 CD ARG D 3 35. .185 69, .243 10, .532 1. ,00 65. .18 6

ATOM 4945 NE ARG D 3 35. ,849 69. .838 11, ,696 1. ,00 66, .90 7

ATOM 4946 CZ ARG D 3 36. .028 71. .141 11. ,888 1. ,00 66. .63 6

ATOM 4947 NHl ARG D 3 35, .591 72, .031 11. ,002 1. ,00 68. .16 7

ATOM 4948 NH2 ARG D 3 36, .664 71, .553 12, .964 1. 00 66. .33 7

ATOM 4949 C ARG D 3 36, .831 66, .719 6, .580 1. .00 59. .10 6

ATOM 4950 O ARG D 3 37, .938 66, .252 6. .845 1. .00 57, .28 8

ATOM 4951 N ALA D 4 35, .909 66, .050 5. .891 1, ,00 56. .67 7

ATOM 4952 CA ALA D 4 36, .153 64, .699 5. .414 1. .00 53, .48 6

ATOM 4953 CB ALA D 4 34, ,938 64, .175 4. .706 1. ,00 52. .26 6

ATOM 4954 C ALA D 4 37, ,347 64, ,696 4, .479 1. ,00 53. ,39 6

ATOM 4955 O ALA D 4 38 .225 63, .851 4, .600 1. .00 52, .40 8

ATOM 4956 N ASP D 5 37, .381 65. .650 3. .550 1. .00 54. ,53 7

ATOM 4957 CA ASP D 5 38 .489 65, .756 2, .602 1. .00 55, .71 6

ATOM 4958 CB ASP D 5 38, ,266 66. .914 1. ,627 1. ,00 58. .22 6

ATOM 4959 CG ASP D 5 36, .938 66. .810 0. ,881 1. .00 61. .46 6

ATOM 4960 ODl ASP D 5 36. ,605 65. ,709 0. ,386 1. ,00 64. .32 8

ATOM 4961 OD2 ASP D 5 36 .227 67 .832 0, ,773 1. .00 63. .22 8

ATOM 4962 C ASP D 5 39, .816 65, .970 3, .326 1. ,00 54, ,28 6

ATOM 4963 O ASP D 5 40, .844 65. .440 2, .914 1. ,00 52. ,86 8

ATOM 4964 N ILE D 6 39, ,787 66. .735 4. .410 1. ,00 52, ,53 7

ATOM 4965 CA ILE D 6 41, .007 67. .003 5. ,154 1. ,00 53, ,69 6

ATOM 4966 CB ILE D 6 40 .813 68. .128 6, .191 1. .00 55, .79 6

ATOM 4967 CG2 ILE D 6 42 .152 68, .435 6, .877 1. .00 54, .61 6

ATOM 4968 CGI ILE D 6 40 .266 69 .385 5 .499 1. .00 55, .83 6

ATOM 4969 CDl ILE D 6 40 .121 70, .597 6, ,400 1. .00 55, .01 6

ATOM 4970 C ILE D 6 41, .545 65, .775 5, ,870 1. .00 52, .43 6

ATOM 4971 O ILE D 6 42 .711 65, .420 5, .709 1. .00 52, ,78 8

ATOM 4972 N LEU D 7 40 .701 65 .134 6, .666 1, .00 51, .01 7

ATOM 4973 CA LEU D 7 41 .111 63 .949 7, .401 1, .00 50 .01 6

ATOM 4974 CB LEU D 7 39 .962 63 .459 8, .276 1, .00 47 .85 6

ATOM 4975 CG LEU D 7 39 .608 64 .420 9, .408 1. .00 46. .02 6

ATOM 4976 CDl LEU D 7 38 .267 64 .084 10, .010 1. .00 48, .59 6

ATOM 4977 CD2 LEU D 7 40 .687 64, .356 10, .440 1. ,00 45. .91 6

ATOM 4978 C LEU- D 7 41 .526 62 .871 6 .415 1 .00 51 .80 6

ATOM 4979 O LEU D 7 42 .507 62, .154 6, .631 1, .00 52, .35 8

ATOM 4980 N TYR D 8 40 .788 62 .781 5 .315 1 .00 52 .55 7

ATOM 4981 CA TYR D 8 41 .060 61 .788 4 .288 1. .00 53, .16 6

ATOM 4982 CB TYR D 8 40 .047 61 .936 3 .159 1 .00 54, .45 6

ATOM 4983 CG TYR D 8 ^•40 .294 61, .006 2 .006 1. .00 57 .19 6

ATOM 4984 CDl TYR D 8 40 .030 59 .646 2 .120 1 .00 57 .12 6

ATOM 4985 CEl TYR D 8 40 .308 58 .772 1 .069 1 .00 60 .62 6

ATOM 4986 CD2 TYR D 8 40 .841 61 .481 0 .810 1 .00 58 .57 6

ATOM 4987 CE2 TYR D 8 41 .130 60 .617 -0 .247 1 .00 60 .35 6

ATOM 4988 CZ TYR D 8 40 .863 59 .264 -0 .112 1. .00 61 .47 6

ATOM 4989 OH TYR D 8 41 .162 58 .403 -1 .149 1, .00 62, .53 8

ATOM 4990 C TYR D 8 42 .483 61 .905 3 .735 1 .00 53 .38 6

ATOM 4991 O TYR D 8 43 .190 60 .907 3 .591 1, .00 53 .74 8 ATOM 4992 N ASN D 9 42.900 63.121 3.416 1.00 53.53 7

ATOM 4993 CA ASN D 9 44.238 63.329 2..890 1.00 55.79 6

ATOM 4994 CB ASN D 9 44.451 64.800 2.509 1.00 59.06 6

ATOM 4995 CG ASN D 9 43.588 65.232 1.317 1.00 63.96 6

ATOM 4996 ODl ASN D 9 42.912 64.406 0.688 1.00 67.47 8

ATOM 4997 ND2 ASN D 9 43.612 66.527 1.000 1.00 65.39 7

ATOM 4998 C ASN D 9 45.283 62.901 3.907 1.00 55.13 6

ATOM 4999 O ASN D 9 46.175 62.117 3.593 1.00 54.15 8

ATOM 5000 N ILE D 10 45.167 63.416 5.129 1. .00 55.13 7

ATOM 5001 CA ILE D 10 46.099 63.077 6.195 1.00 54.61 6

ATOM 5002 CB ILE D 10 45.660 63.693 7.534 1.00 54.44 6

ATOM 5003 CG2 ILE D 10 46.585 63.218 8.651 1.00 53.71 6

ATOM 5004 CGI ILE D 10 45.683 65.222 7.435 .00 52.93 6

ATOM 5005 CDl ILE D 10 45.083 65.916 8.605 .00 47.92 6

ATOM 5006 C ILE D 10 46.177 61.566 6.365 .00 56.15 6

ATOM 5007 O ILE D 10 47.258 60.992 6.496 .00 57.11 8

ATOM 5008 N ARG D 11 45.018 60.927 6.363 .00 56.48 7

ATOM 5009 CA ARG D 11 44.938 59.494 6.512 .00 58.41 6

ATOM 5010 CB ARG D 11 43.478 59.070 6.428 ,00 63.58 6

ATOM 5011 CG ARG D 11 43.229 57.585 6.631 1.00 70.33 6

ATOM 5012 CD ARG D 11 43.398 57.219 8.100 1.00 79.03 6

ATOM 5013 NE ARG D 11 42.703 55.980 8.448 1.00 85.37 7

ATOM 5014 CZ ARG D 11 41.466 55.685 8.037 1.00 88.61 6

ATOM 5015 NHl ARG D 11 40.795 56.548 7.249 1.00 89.11 7

ATOM 5016 NH2 ARG D 11 40.890 54.545 8.434 1.00 87.93 7

ATOM 5017 C ARG D 11 45.721 58.778 5..425 1.00 58.93 6

ATOM 5018 O ARG D 11 46.497 57.862 5.698 .00 58.85 8

ATOM 5019 N GLN D 12 45.507 59.211 4.186 .00 59.05 7

ATOM 5020 CA GLN D 12 46.131 58.596 3.024 00 57.95 6

ATOM 5021 CB GLN D 12 45.345 58.958 1..780 00 57.48 6

ATOM 5022 CG GLN D 12 44.961 57.767 0.955 1.00 61.67 6

ATOM 5023 CD GLN D 12 43.773 57.069 1.525 1.00 61.71 6

ATOM 5024 OEl GLN D 12 42.729 57.685 1.698 1.00 64.71 8

ATOM 5025 NE2 GLN D 12 43.912 55.784 1.831 1.00 59.81 7

ATOM 5026 C GLN D 12 47.589 58.926 .769 1.00 57.99 6

ATOM 5027 O GLN D 12 48.280 58.169 .097 1.00 58.62 8

ATOM 5028 N THR D 13 48.070 60.046 .291 1.00 57.97 7

ATOM 5029 CA THR D 13 49.452 60.433 .042 1.00 58.22 6

ATOM 5030 CB THR D 13 49.520 61.855 .464 00 56.90 6

ATOM 5031 OG1 THR D 13 48.907 62.774 3.377 00 53.15 8

ATOM 5032 CG2 THR D 13 48.808 61.923 1.110 00 56.04 6

ATOM 5033 C THR D 13 50.361 60.394 4.255 00 60.59 6

ATOM 5034 O THR D 13 51.589 60.416 4.120 ,00 61.33 8

ATOM 5035 N SER D 14 49.762 60.335 5.440 1.00 61.87 7

ATOM 5036 CA SER D 14 50.542 60.332 6.669 1.00 61.93 6

ATOM 5037 CB SER D 14 49.634 60.613 7.863 1.00 61.53 6

ATOM 5038 OG SER D 14 50.417 60.962 8.988 1.00 62.76

ATOM 5039 C SER D 14 51.323 59.035 6.903 1.00 61.38

ATOM 5040 O SER D 14 50.922 57.950 6.467 1.00 62.07

ATOM 5041 N ARG D 15 52.444 59.175 7.596 1.00 59.21

ATOM 5042 CA ARG D 15 53.317 58.061 7.911 1.00 58.97

ATOM 5043 CB ARG D 15 54.553 58.087 7.011 1.00 59.72

ATOM 5044 CG ARG D 15 54.219 57.978 5, .528 1.00 62.38

ATOM 5045 CD ARG D 15 55.455 57.608 4..738 1 .00 63.96

ATOM 5046 NE ARG D 15 56.013 56.364 5.254 1.00 66.53

ATOM 5047 CZ ARG D 15 57.207 55.873 4.929 1.00 66.36

ATOM 5048 NHl ARG D 15 57.985 56.528 4.080 1.00 65.36

ATOM 5049 NH2 ARG D 15 57.623 54.721 5.457 1.00 67.99

ATOM 5050 C ARG D 15 53.724 58.182 9.376 1.00 57.69

ATOM 5051 O ARG D 15 54.705 58.859 9.715 1.00 57.96

ATOM 5052 N PRO D 16 52.967 57.517 10.265 1.00 55.24 ATOM 5053 CD PRO D 16 51.785 56.700 9.935 1.00 51.06 6

ATOM 5054 CA PRO D 16 53. 200 57. 524 11. ,709 1. 00 51. 86 6

ATOM 5055 CB PRO D 16 52. 104 56. 602 12. ,236 1. 00 49. 85 6

ATOM 5056 CG PRO D 16 51. 031 56. 720 11. 226 1. 00 51. 02 6

ATOM 5057 C PRO D 16 54. 580 57. 066 12. 130 1. 00 49. 97 6

ATOM 5058 O PRO D 16 55. 034 57. 387 13. ,220 1. 00 48. 83 8

ATOM 5059 N ASP D 17 55. 247 56. 313 11. 270 1. 00 50. 05 7

ATOM 5060 CA ASP D 17 56. ,568 55. .809 11. ,612 1. 00 53. ,82 6

ATOM 5061 CB ASP D 17 56. ,796 54. ,419 10. ,981 1. ,00 57. .43 6

ATOM 5062 CG ASP D 17 55. ,979 53. .320 11. .666 1. ,00 63. .55 6

ATOM 5063 ODl ASP D 17 55. ,728 53. 431 12. ,892 1. 00 63. ,43 8

ATOM 5064 OD2 ASP D 17 55. ,598 52. 330 10. ,985 1. 00 66. ,47 8

ATOM 5065 C ASP D 17 57. ,710 56. .733 11, .218 1. ,00 52. .72 6

ATOM 5066 O ASP D 17 58. ,875 56. ,406 11, .4.40 1. 00 54. .00 8

ATOM ^' 5067 N VAL D 18 57. .384 57. .888 10, .653 1. ,00 50. .54 7

ATOM 5068 CA VAL D 18 58. ,418 58. ,808 10, ,209 1. ,00 51. .72 6

ATOM 5069 CB VAL D 18 58. .353 58. .992 8, .680 1, .00 52, ,70 6

ATOM 5070 CGI VAL D 18 59, ,487 59. .869 8, .209 1. ,00 52. ,67 6

ATOM 5071 CG2 VAL D 18 58, .426 57. ,642 7, .998 1. ,00 53. .16 6

ATOM 5072 C VAL D 18 58, .402 60, .181 10 .865 1. .00 51. .90 6

ATOM 5073 O VAL D 18 57. .463 60. .955 10, .716 1. ,00 50, .79 8

ATOM 5074 N ILE D 19 59, ,475 60. .473 11 .586 1, .00 52 .81 7

ATOM 5075 CA ILE D 19 59, ,646 61. .748 12, .280 1. .00 54, .09 6

ATOM 5076 CB ILE D 19 60. .960 61. .699 13, .116 1. ,00 53, .08 6

ATOM 5077 CG2 ILE D 19 62. .168 61. .565 12, .194 1. ,00 53, .31 6

ATOM 5078 CGI ILE D 19 61, .074 62. .919 14, .027 1. ,00 52, .13 6

ATOM 5079 CDl ILE D 19 62, .157 62. .753 15, .086 1. ,00 49, .47 6

ATOM 5080 C ILE D 19 59. .675 62, .907 11 .255 1. ,00 56, .58 6

ATOM 5081 O ILE D 19 60 .436 62 .877 10 .274 1 .00 57 .79 8

ATOM 5082 N PRO D 20 58 .833 63 .936 11 .464 1 .00 56 .89 7

ATOM 5083 CD PRO D 20 57 .915 64, .059 12 .603 1 .00 56 .43 6

ATOM 5084 CA PRO D 20 58 .725 65, .113 10 .587 1, .00 58, .17 6

ATOM 5085 CB PRO D 20 57 .505 65, .856 11 .148 1, .00 57 .33 6

ATOM 5086 CG PRO D 20 56 .812 64, .848 12 .009 1, .00 56 .81 6

ATOM 5087 C PRO D 20 59 .985 66 .004 10 .585 1, .00 60 .38 6

ATOM 5088 O PRO D 20 59 .920 67 .215 10 .802 1, .00 57 .93 8

ATOM 5089 N THR D 21 61 .128 65 .391 10 .329 1, .00 64 .41 7

ATOM 5090 CA THR D 21 62 .392 66 .106 10 .320 1 .00 68 .99 6

ATOM 5091 CB THR D 21 63 .546 65 .121 10 .552 1 .00 68 .83 6

ATOM 5092 OG1 THR D 21 63 .899 65 .152 11 .939 1 .00 69 .74 8

ATOM 5093 CG2 THR D 21 64 .760 65 .457 9 .688 1 .00 69 .49 6

ATOM 5094 C THR D 21 62 .671 66 .926 9 .067 1 .00 73 .81 6

ATOM 5095 O THR D 21 62 .480 66 .457 7 .936 1 .00 75 .27 8

ATOM 5096 N GLN D 22 63 .130 68, .157 9 .285 1 .00 77 .41 7

ATOM 5097 CA GLN D 22 63 .481 69 .076 8 .203 1 .00 81 .17 6

ATOM 5098 CB GLN D 22 62 .791 70 .416 8 .428 1 .00 82 .19 6

ATOM 5099 CG GLN D 22 61 .281 70 .306 8 .543 1 .00 84 .72 6

ATOM 5100 CD GLN D 22 60 .689 71 .416 9 .409 1 .00 86 .15 6

ATOM 5101 OEl GLN D 22 60 .939 71 .471 10 .623 1 .00 85 .03 8

ATOM 5102 NE2 GLN D 22 59 .901 72 .309 8 .789 1 .00 86 .55 7

ATOM 5103 C GLN D 22 65 .001 69 .262 8 .233 1 .00 83 .27 6

ATOM 5104 0 GLN D 22 65 .538 69 .912 9 .147 1 .00 83 .34 8

ATOM 5105 N ARG D 23 ^•65 .691 68 .686 7 .243 1 .00 85 .66 7

ATOM 5106 CA ARG D 23 67 .159 68 .767 7 .170 1 .00 87 .34 6

ATOM 5107 CB ARG D 23 67 .625 70 .231 7 .105 1 .00 88 .19 6

ATOM 5108 CG ARG D 23 67 .453 70 .875 5 .742 1 .00 89 .83 6

ATOM 5109 CD ARG D 23 66 .246 71 .822 5 .674 1 .00 92 .72 6

ATOM 5110 NE ARG D 23 65 .994 72 .293 4 .298 1 .00 95 .59 7

ATOM 5111 CZ ARG D 23 66 .904 72 .868 3 .497 ^■ 1 .00 95 .46 6

ATOM 5112 NHl ARG D 23 68 .158 73 .068 3 .914 1 .00 93 .60 7

ATOM 5113 NH2 ARG D 23 66 .555 73 .226 2 .257 1 .00 94 .84 7 ATOM 5114 C ARG D 23 67.768 68.079 8.399 1.00 87.43 6

ATOM 5115 O ARG D 23 67. 201 67. 105 8. 907 1. 00 88. 35 8

ATOM 5116 N ASP D 24 68. 912 68. 570 8. ,875 1. 00 87. 68 7

ATOM 5117 CA ASP D 24 69. 538 67. ,975 10. .055 1. 00 86. ,96 6

ATOM 5118 CB ASP D 24 71. 041 68. 283 10. 123 1. 00 91. 11 6

ATOM 5119 CG ASP D 24 71. ,627 68. ,719 8. .780 1. 00 94. ,40 6

ATOM 5120 ODl ASP D 24 71. 599 67. 908 7. ,806 1. 00 95. ,87 8

ATOM 5121 OD2 ASP D 24 72. 121 69. 881 8. 712 1. 00 95. 25 8

ATOM 5122 C ASP D 24 68. 864 68. 594 11. ,274 1. 00 85. 02 6

ATOM 5123 O ASP D 24 69. .279 68. ,347 12. ,414 1. 00 83. ,40 8

ATOM 5124 N ARG D 25 67. ,836 69. ,409 11. .026 1. 00 82. ,95 7

ATOM 5125 CA ARG D 25 67. ,112 70. 062 12. 111 1. 00 81. 58 6

ATOM 5126 CB ARG D 25 66. ,218 71. ,189 11. .585 1. 00 83. ,67 6

ATOM 5127 CG ARG D 25 66. ,951 72. ,455 11. ,150 1. 00 88. ,52 6

ATOM 5128 CD ARG D 25 65. .941 73, .597 10, .942 1. ,00 92. .65 6

ATOM 5129 NE ARG D 25 66. ,579 74. .866 10. .584 1. ,00 96, .29 7

ATOM 5130 CZ ARG D 25 65. ,928 76. ,024 10. ,463 1. 00 98. ,03 6

ATOM 5131 NHl ARG D 25 64. ,608 76. .073 10. .673 1. ,00 98. .35 7

ATOM 5132 NH2 ARG D 25 66. .597 77. .136 10. .142 1. 00 98. .69 7

ATOM 5133 C ARG D 25 66. ,241 69. .091 12. .901 1. ,00 78. ,66 6

ATOM 5134 O ARG D 25 65. .480 68. ,303 12. .325 1. .00 79. ,51 8

ATOM 5135 N PRO D 26 66. ,353 69. .127 14, .237 1, .00 74, ,94 7

ATOM 5136 CD PRO D 26 67, .383 69, .831 15, .020 1. .00 73, .76 6

ATOM 5137 CA PRO D 26 65, .562 68. .252 15, .101 1. ,00 71. .13 6

ATOM 5138 CB PRO D 26 66 .202 68, .450 16 .483 1. .00 71 .49 6

ATOM 5139 CG PRO D 26 67, .608 68, .884 16, .165 1, ,00 72. .18 6

ATOM 5140 C PRO D 26 64, .115 68. .738 15. .095 1. .00 67, .33 6

ATOM 5141 O PRO D 26 63. .834 69. .874 14. .713 1. ,00 65. .48 8

ATOM 5142 N VAL D 27 63. .198 67. .870 15, .510 1. .00 63, .87 7

ATOM 5143 CA VAL D 27 61, .806 68. .258 15, .596 1. .00 58, .65 6

ATOM 5144 CB VAL D 27 60, .849 67. .036 15, .494 1. .00 57, .16 6

ATOM 5145 CGI VAL D 27 59, .462 67. .401 15, .998 1. .00 54, .11 6

ATOM 5146 CG2 VAL D 27 60 .755 66, .579 14, .052 1, .00 56, .19 6

ATOM 5147 C VAL D 27 61 .705 68. .896 16 .968 1, .00 56 .92 6

ATOM 5148 O VAL D 27 62, .164 68. .337 17, .961 1. .00 55. .97 8

ATOM 5149 N ALA D 28 61. .136 70. .088 17, .019 1. ,00 56, ,42 7

ATOM 5150 CA ALA D 28 60 .999 70. .767 18, .287 1. .00 55, ,56 6

ATOM 5151 CB ALA D 28 61 .057 72, .269 18 .095 1, .00 55 .33 6

ATOM 5152 C ALA D 28 59. .688 70, .371 18, .923 1. .00 54, .28 6

ATOM 5153 O ALA D 28 58 .617 70 .741 18 .440 1, .00 54 .43 8

ATOM 5154 N VAL D 29 59 .800 69 .603 20 .006 1, .00 52 .62 7

ATOM 5155 CA VAL D 29 58 .657 69 .127 20 .775 1. .00 50 .60 6

ATOM 5156 CB VAL D 29 58 .715 67 .599 21 .016 1, .00 48 .93 6

ATOM 5157 CGI VAL D 29 57 .543 67 .162 21 .871 1 .00 46 .20 6

ATOM 5158 CG2 VAL D 29 58 .718 66 .868 19 .692 1 .00 47 .60 6

ATOM 5159 C VAL D 29 58 .652 69, .805 22 .131 1, .00 50 .77 6

ATOM 5160 O VAL D 29 59 .657 69 .806 22 .852 1, ,00 51 .59 8

ATOM 5161 N SER D 30 57 .517 70 .395 22 .471 1 .00 50 .31 7

ATOM 5162 CA SER D 30 57 .373 71 .049 23 .754 1 .00 52 .56 6

ATOM 5163 CB SER D 30 56 .794 72 .449 23 .575 1 .00 53 .44 6

ATOM 5164 OG SER D 30 55 .514 72 .393 22 .966 1 .00 56 .80 8

ATOM 5165 C SER D 30 56 .442 70 .188 24 .598 1 .00 53 .29 6

ATOM 5166 O SER D 30 55 .397 69 .746 24 .126 1 .00 55 .20 8

ATOM 5167 N VAL D 31 56 .845 69 .947 25 .841 1, .00 54 .04 7

ATOM 5168 CA VAL D 31 56 .089 69 .130 26 .780 1 .00 56 .25 6

ATOM 5169 CB VAL D 31 56 .911 67 .898 27 .241 1 .00 58 .16 6

ATOM 5170 CGI VAL D 31 56 .015 66 .914 27 .986 1 .00 56 .17 6

ATOM 5171 CG2 VAL D 31 57 .573 67 .234 26 .043 1 .00 58 .28 6

ATOM 5172 C VAL D 31 55 .753 69 .947 28 .015 1 .00 57 .41 6

ATOM 5173 O VAL D 31 56 .607 70 .632 28 .570 1 .00 58 .01 8

ATOM 5174 N SER D 32 54 .508 69 .850. 28 .458 1 .00 59 .19 7 ATOM 5175 CA SER D 32 54.,062 70..594 29.,628 1.00 59.47 6

ATOM 5176 CB SER D 32 53. 467 71. ,934 29. ,175 1. 00 60. 04 6

ATOM 5177 OG SER D 32 52. .892 72. .641 30. ,256 1. ,00 62. ,30 8

ATOM 5178 C SER D 32 53. ,023 69. ,799 30. ,433 1. 00 58. 78 6

ATOM 5179 O SER D 32 51. ,906 69 . ,572 29. ,966 1. 00 59. 54 8

ATOM 5180 N LEU D 33 53. ,390 69. .379 31. .638 1. ,00 56. ,81 ^' 7

ATOM 5181 CA LEU D 33 52. ,468 68. 629 32. 472 1. 00 56. 85 6

ATOM 5182 CB LEU D 33 53. .217 67. .702 33. .426 1. .00 54. ,23 6

ATOM 5183 CG LEU D 33 54. ,192 66. ,726 32. ,775 1. 00 55. 08 6

ATOM 5184 CDl LEU D 33 54. ,665 65. ,709 33. .818 1. .00 53. .15 6

ATOM 5185 CD2 LEU D 33 53. ,513 66. ,034 31. .614 1. ,00 54. ,80 6

ATOM 5186 C LEU D 33 51. .623 69. .572 33. .291 1. ,00 56. ,91 6

ATOM 5187 O LEU D 33 52. ,136 70. .542 33. .829 1. ,00 59. ,29 8

ATOM 5188 N LYS D 34 50. .327 69. ,294 33. .366 1. ,00 56. ,10 7

ATOM 5189 CA LYS D 34 49. .422 70. ,089 34. .171 1. ,00 55. ,13 6

ATOM 5190 CB LYS D 34 48, .311 70. .694 33. .320 1. ,00 58. .38 6

ATOM 5191 CG LYS D 34 48. .802 71. .519 32. ,146 1. ,00 65. ,52 6

ATOM 5192 CD LYS D 34 49. .581 72. .764 32. ,581 1. ,00 69. ,06 6

ATOM 5193 CE LYS D 34 50. ,100 73. .559 31. ,364 1. ,00 72. ,37 6

ATOM 5194 NZ LYS D 34 50, .855 74. .801 31, .747 1. .00 72. ,05 7

ATOM 5195 C LYS D 34 48. .838 69, .065 35, .118 1. ,00 53. ,80 6

ATOM 5196 O LYS D 34 48. .123 68, .167 34. .685 1. ,00 55. ,04 8

ATOM 5197 N PHE D 35 49. .144 69. .173 36. .405 1. .00 51. ,60 7

ATOM 5198 CA PHE D 35 48. .616 68, .200 37, ,346 1. ,00 49. ,19 6

ATOM 5199 CB PHE D 35 49, .441 68. .199 38. .616 1. ,00 46, ,49 6

ATOM 5200 CG PHE D 35 50, .838 67. .733 38. .393 1. ,00 48. ,31 6

ATOM 5201 CDl PHE D 35 51. .823 68, .617 37, .964 1. ,00 46, .94 6

ATOM 5202 CD2 PHE D 35 51, .159 66. .387 38, .530 1. ,00 49. .16 6

ATOM 5203 CEl PHE D 35 53. .109 68, .170 37, .668 1. .00 48, .04 6

ATOM 5204 ^'CE2 PHE D 35 52, .449 65, .925 38, .235 1. ,00 50, .28 6

ATOM 5205 CZ PHE D 35 53 .424 66 .818 37, .802 1. .00 48, .13 6

ATOM 5206 C PHE D 35 47, .136 68, .352 37, .642 1. .00 49. .07 6

ATOM 5207 O PHE D 35 46 .626 69, .449 37, .869 1. .00 49, .57 8

ATOM 5208 N ILE D 36 46 .451 67 .217 37 .600 1. .00 47 .68 7

ATOM 5209 CA ILE D 36 45, .030 67, .156 37, .827 1. .00 44. .72 6

ATOM 5210 CB ILE D 36 44 .352 66 .334 36 .731 1 .00 43 .48 6

ATOM 5211 CG2 ILE D 36 42, .850 66, .369 36, .914 1. .00 41. .45 6

ATOM 5212 CGI ILE D 36 44 .752 66 .877 35 .360 1 .00 43 .86 6

ATOM 5213 CDl ILE D 36 44 .398 68, .324 35, .152 1. .00 46, .64 6

ATOM 5214 C ILE D 36 44 .719 66. .525 39, .164 1. .00 44, .81 6

ATOM 5215 O ILE D 36 43 .677 66 .798 39 .743 1. .00 46, .51 8

ATOM 5216 N ASN D 37 45 .612 65 .678 39, .661 1, .00 42 .08 7

ATOM 5217 CA ASN D 37 45 .363 65 .030 40 .939 1 .00 42 .31 6

ATOM 5218 CB ASN D 37 44 .117 64 .140 40 .834 1, .00 41 .66 6

ATOM 5219 CG ASN D 37 43 .392 63 .990 42 .159 1. .00 43 .88 6

ATOM 5220 ODl ASN D 37 44 .015 63 .785 43 .200 1 .00 43 .62 8

ATOM 5221 ND2 ASN D 37 42 .068 64 .085 42 .124 1 .00 38 .41 7

ATOM 5222 C ASN D 37 46 .539 64 .186 41 .426 1 .00 43 .81 6

ATOM 5223 O ASN D 37 47 .380 63 .752 40 .640 1 .00 40 .93 8

ATOM 5224 N ILE D 38 46 .588 63 .977 42 .740 1 .00 43 .93 7

ATOM 5225 CA ILE D 38 47 .612 63 .163 43. .372 1 .00 44 .58 6

ATOM 5226 CB ILE D 38 48 .496 64 .013 44 .246 1 .00 42 .93 6

ATOM 5227 CG2 ILE D 38 ^•49 .473 63 .140 44 .989 1 .00 39 .88 6

ATOM 5228 CGI ILE D 38 49 .220 65 .028 43 .359 1 .00 43 .19 6

ATOM 5229 CDl ILE D 38 49 .944 66 .110 44 .084 1 .00 44 .94 6

ATOM 5230 C ILE D 38 46 .795 62 .183 44 .190 1 .00 47 .97 6

ATOM 5231 O ILE D 38 46 .169 62 .565 45 .162 1 .00 50 .60 8

ATOM 5232 N LEU D 39 46 .802 60 .916 43 .777 1 .00 50 .68 7

ATOM 5233 CA LEU D 39 45 .979 59 .874 44 .388 1 .00 51 .24 6

ATOM 5234 CB LEU D 39 45 .489 58 .944 43 .287 1 .00 51 .95 6

ATOM 5235 CG LEU D 39 44 .834 59 .723 42 .141 1 .00 54 .64 6 ATOM 5236 CDl LEU D 39 44.,356 58.,777 41.,068 1.,00 53.,53 6

ATOM 5237 CD2 LEU D 39 43. ,666 60. 542 42. ,696 1. 00 53. .70 6

ATOM 5238 C LEU D 39 46, .520 59. ,041 45. ,529 1. 00 53. 82 6

ATOM 5239 O LEU D 39 45, .793 58. ,750 46. ,479 1. ,00 54. ,77 8

ATOM 5240 N GLU D 40 47. ,771 58. 620 45. ,437 1. 00 54. 21 7

ATOM 5241 CA GLU D 40 48, ,349 57. .825 46. .507 1. ,00 56. ,24 6

ATOM 5242 CB GLU D 40 48, .278 56. .339 46. .204 1. ,00 58. ,19 6

ATOM 5243 CG GLU D 40 46, .873 55. ,801 46. ,103 1. ,00 65. ,00 6

ATOM 5244 CD GLU D 40 46. .844 54. ,291 45. ,938 1. ,00 68. ,23 6

ATOM 5245 OEl GLU D 40 47, .443 53. .791 44, ,955 1. ,00 70. ,63 8

ATOM 5246 OE2 GLU D 40 46, .226 53. .611 46. .789 1. ,00 68. ,96 8

ATOM 5247 C GLU D 40 49. .785 58. .198 46, .702 1. ,00 56. .38 6

ATOM 5248 O GLU D 40 50, .541 58. .355 45, .746 1. ,00 59. .25 8

ATOM 5249 N VAL D 41 50, .162 58. .343 47, .955 1. .00 55. ,49 7

ATOM 5250 CA VAL D 41 51, .517 58. .695 48, .273 1, ,00 54. ,71 6

ATOM 5251 CB VAL D 41 51. .590 60. .145 48, .811 1. .00 55, .08 6

ATOM 5252 CGI VAL D 41 52, .954 60. ,431 49. .361 1. .00 55, ,65 6

ATOM 5253 CG2 VAL D 41 51 .273 61 .125 47, .696 1, .00 55. .07 6

ATOM 5254 C VAL D 41 52. .003 57. ,713 49, .309 1. .00 54, .17 6

ATOM 5255 O VAL D 41 51, .232 57. .239 50, .136 1. .00 53. ,51 8

ATOM 5256 N ASN D 42 53. .280 57. ,381 49. .233 1. ,00 54. ,90 7

ATOM 5257 CA ASN D 42 53. .880 56, .473 50. .182 1. ,00 56. ,47 6

ATOM 5258 CB ASN D 42 53. .944 55. ,056 49. .612 1. ,00 55, .97 6

ATOM 5259 CG ASN D 42 54 .306 54, .025 50. .661 1. ,00 56. .38 6

ATOM 5260 ODl ASN D 42 55 .272 54, .191 51, .408 1. ,00 55. .15 8

ATOM 5261 ND2 ASN D 42 53 .536 52, .947 50, .717 1. ,00 56, .12 7

ATOM 5262 C ASN D 42 55 .278 57, .022 50 .420 1. .00 58. .56 6

ATOM 5263 0 ASN D 42 56, .154 56, .912 49. .567 1. ,00 58. .83 8

ATOM 5264 N GLU D 43 55 .474 57, .639 51 .579 1. ,00 59. .69 7

ATOM 5265 CA GLU D 43 56 .771 58 .208 51 .905 1. .00 60, .97 6

ATOM 5266 CB GLU D 43 56 .640 59 .192 53 .065 1. .00 63, .50 6

ATOM 5267 CG GLU D 43 57 .921 59, .959 53 .341 1, .00 67, .19 6

ATOM 5268 CD GLU D 43 57, .725 61, .121 54. .303 1. .00 68. .84 6

ATOM 5269 OEl GLU D 43 58 .743 61 .734 54 .682 1. ,00 70 .83 8

ATOM 5270 OE2 GLU D 43 56 .568 61, .427 54. .670 1. .00 67, .80 8

ATOM 5271 C GLU D 43 57 .792 57 .134 52 .246 1. .00 59, .80 6

ATOM 5272 O GLU D 43 58 .993 57 .356 52 .138 1. .00 59 .85 8

ATOM 5273 N ILE D 44 57 .301 55 .969 52, .653 1, .00 59 .27 7

ATOM 5274 CA ILE D 44 58 .164 54, .858 53, .006 1, .00 59 .05 6

ATOM 5275 CB ILE D 44 57, .373 53, .723 53, .681 1. ,00 59, .62 6

ATOM 5276 CG2 ILE D 44 58 .300 52 .527 53 .945 1, .00 59 .50 6

ATOM 5277 CGI ILE D 44 56 .752 54 .217 54 .982 1, .00 58 .87 6

ATOM 5278 CDl ILE D 44 57 .768 54 .484 56 .073 1, .00 60 .45 6

ATOM 5279 C ILE D 44 58 .801 54, .286 51, .751 1. .00 59, .04 6

ATOM 5280 O ILE D 44 60 .001 54 .029 51. .723 1. .00 60, .06 8

ATOM 5281 N THR D 45 57 .986 54, .080 50, .719 1. ,00 57, .12 7

ATOM 5282 CA THR D 45 58 .461 53, .513 49, .464 1, ,00 54, .05 6

ATOM 5283 CB THR D 45 57 .410 52 .576 48 .857 1, .00 52 .43 6

ATOM 5284 OG1 THR D 45 56 .204 53 .304 48 .628 1, .00 49 .39 8

ATOM 5285 CG2 THR D 45 57 .128 51 .426 49 .788 1, .00 49 .70 6

ATOM 5286 C THR D 45 58 .833 54, .551 48, .417 1. .00 53, .32 6

ATOM 5287 O THR D 45 59 .427 54, .215 47, .397 1. ,00 56, .15 8

ATOM 5288 N ASN D 46 58 .493 55 .809 48 .666 1 .00 51 .82 7

ATOM 5289 CA ASN D 46 58 .796 56 .874 47 .723 1 .00 51 .33 6

ATOM 5290 CB ASN D 46 60 .305 57 .022 47 .567 1 .00 51 .66 6

ATOM 5291 CG ASN D 46 60 .874 58 .117 48 .434 1, .00 52 .73 6

ATOM 5292 ODl ASN D 46 62 .057 58 .105 48 .765 1 .00 52 .55 8

ATOM 5293 ND2 ASN D 46 60 .041 59 .078 48 .793 1, .00 50 .90 7

ATOM 5294 C ASN D 46 58 .156 56 .618 46 .360 1, .00 50 .97 6

ATOM 5295 O ASN D 46 58 .820 56 .668 45 .325 1 .00 53 .17 8

ATOM 5296 N GLU D 47 56 .858 56 .348 46 .371 1 .00 48 .99 7

^ ; t |w ;_y !_-_*to ^ to ;)» |> ^ !_3 ' to to to to to to

!-3^ι^ 3 3 3 3>-3ι-3βι- >- β^μ3ββι-3 aβHvθββββββι-3ι-3ι-3βHβι-3^βββ>-3^>^

OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOσOOOOOOOOOOOOOOQOQOQOQOOQQ ggggggggggggglξgggggSSggggSgggggggggggSgggKgSgggggggggggggggg π π Lπ Lπ Lπ Lπ Lπ Lπ Lπ π ^

L LO LO C_0 (__J L~l L^

Lπ Lπ Lπ ~j c Ln LO M P-> o co -3 _-' o

Ω Ω Ω Ω a Ω O Ω O Ω Ω Ω S O OΩΩΩΩΩΩΩΩS Ω Ω Ω Ω Ω a O O a O O O Ω a O Ω O Ω O O Ω Ω Ω

5! N N W α tS H t) O tJ] ι N M B tj α n to Ω Ω ft⁾ Ω Ω ft) ϋ ϋ Ω Ed ∑ Ω Ω td t c m α Ω ω to ω to μ p tiJ to to t P M P co μ-> CO to p to P to μ-> ι-3 3 ι-3 ^ 3 ^ ι^ ι-3 β β '-3 β '-3 ^ ^ ^ ^ 'xi ^ « ^ fl ^ ^ < < < < < < < < < <! ' &=^{, ,} !fc' ^ << < < < < ΩΩΩ ΩΩ Ω Ω pd p p pd pd d pd p p p p p p ffi K ffi ffi ffi ffi ffi W ffi ffi W ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ to to 5 to <t-'t t-¹ t-^, t-^t tr^l t-^|

^ ^l~ ^|rJ ^{h l}x) ^t _J ⁱ t^ι t^| _H f^ι t^, c; d α α α i c! αααoααoσααααoαoαααααααooα

__ι uι uι uι ι_ι uι (_ι (jι Uι uι Oι uι Uι uι Ui ui uι ω ui u: W u ui uι uι uι w uι uι αι tn αι __n ω tjι uι uι ui ι^ ^ ω ω ω ω ω ω ω ω ω ω ω ω ij to to to to to to to to to to to p p p p p p p o o o o o o o ω uJ w io ω ω so ω txi ffi co αj αi oj

_jι ~ -o ∞ o w Lπ tsJ Lπ cxι σι Lπ (_π o -J to o-ι c__o o c_n cn oo c_o _)-. cn -~a L^ co μ-' to tso -o -J cn -J sD W w ω o -o μ^ co .f-. cn ∞ so Lo .f^ to cn o

(jι u p _o p ~ι m t ^ ~ι io m ^ oι θ o fc w ι_3 si μ tji fc σι o u) θ J θ J cn ι_ι p co oo P o t m J m (Λ ~l p p p _o _o p si uι uι p to co σi -θ m c -j -o σι o-ι o-i w-ι θ-ι c w-ι o-ι σι o-ι σ σι o o oo c_ rι D co co ~J ~ σι L tsj ^j ω L O L ω ω ω ω ω ω L L Lo L Lo L L Lo t^ ω LO o oj ω ω

O P P P - P P P P P O P t _ W ω ιl- I tΛ lJ fc _i _i Ul M (Λ J 01 ~l ~] CO J (B O CO w U) O W P P O P - P t P _O ι|i lJ U lι ω ι_n θl Ul (ι Ul U tn σι P w P tD o co u u ιo _ oι cιι t p ⁽jι *, o o iιj ι_) ~] iΛj __j (Λ (iι ι *> ιo ^ ~l m o J iD io ω ι>J Ui ~l *> uι _jι iD iD flι m m W uι ι ιo p p ω σι o o p ^ p u ~l ^ m p ιn o3 iD ιti Ui ~] P ιl- m o ιl- t)) ω _n iB iιi - tΛ _ p -rι o ^ o w p oι [B (» ) ~i M μ io o ω t p p vj t oi o io ω to p io ^ p o o o o uι ω p u ~ι uι ω m co w ω o μ uι oi vi ijι co to _i co π) i_) (s ω u o <s u μ o j μ o <ιι M>ι o -j so co uι o o j ω o t - ω m uι μ p _- (» σι uι μ-> μ-> μ^Λ μ^j μ^j μ-' μ-^, ι-' i-' i-^λ μ-^Λ μ-' μ-^ι H^> μ-^> μ' ^ι μ-^ι μ^j μ^j. μ^j μ^Λ i-' i-' μ-' t-> t-> ι-» H> μ-> μ-^> μ^j μ-^> μ-^l μ-^> μ-^l μ-> μ^j μ-^, μ-ⁱ ι-' μ-' μ^j (-^ι μ-^l μ^j μ-' μ-> μ^Λ μ-^» (-¹ ι-^Λ μ-^l μ-^ι μ-^ι μ-^ι μ-^ι oooooo ooooooooooooo ooooooooooαooo o o ooooσooooooooσooooooo o o ooooooooooooooooooooooooooooooooooo o o ooooσoooooooooooooσoo o o ι^ Ln Lπ Ln ι)-. ιl^ Ln Lπ ,|-~. ιl^ _.|~. _.l-. _l|--> , .^ ₁|--, ₁l_-_. _l|---. ,|---. .|---. ,|__. ι^ ι^ ι^ ιl^ ι^ ι^ ι^ Ln uι ι i ι(-- ι_- ui Ln uι t_π uι uι uι ijι uι ui ιii. ιi_^ ι(i ι^

01 U *ι t α) J M O l_) 01 Ul ιM>J m ι^ P K) _0 _ f. t P -0 0 01 t0 01 lO ~I Q P σι (- ιt> lD ιo ~ι ccι co ιo ~ι u uι t iD iD ω P ι σι ω _ o o o p co ιo ~ι oι μ^j μ-> ω t Lπ w - ι ι _o o o i Lπ o ιl-. s o ~ M χ) n μ^ ~J ιl^ ρ^j o- μj ιi^ ι(-. so sΩ θθ ι^ - o ω ω so cι to -~J -J cn o oo so t__n o t ιJ ^ o μ^j -J ^ Co ~j σι __^ ~J Ui c» c?ι cn c o^ -J -i w θ-v wΛ w-i w-ι w-ι -j oo <^ σι _ σι cn w-ι o θΛ θ^ ~J c_o u^

ATOM 5358 O TRP D 53 49.803 67.384 30.960 1.00 46.13

ATOM 5359 N GLN D 54 49.444 65.532 29.760 1.00 49.02

ATOM 5360 CA GLN D 54 50.741 65.592 29.112 1.00 48.49

ATOM 5361 CB GLN D 54 51.248 64.184 28.809 1.00 48.38

ATOM 5362 CG GLN D 54 52.677 64.135 28.317 1.00 50.78

ATOM 5363 CD GLN D 54 53.339 62.792 28.583 1.00 52.08

ATOM 5364 OEl GLN D 54 53.409 62.336 29.721 ,00 52.24

ATOM 5365 NE2 GLN D 54 53.832 62.158 27.532 .00 53.79

ATOM 5366 C GLN D 54 50.560 66.408 27.849 ,00 49.01

ATOM 5367 O GLN D 54 50.504 65.892 26.735 ,00 48.80

ATOM 5368 N GLN D 55 50.441 67.708 28.058 1.00 51.39

ATOM 5369 CA GLN D 55 50.256 68.665 26.985 1.00 53.26

ATOM 5370 CB GLN D 55 49.964 70.022 27.609 1.00 56.68

ATOM 5371 CG GLN D 55 49.913 71.176 26.652 1.00 66.24 6

ATOM 5372 CD GLN D 55 49.355 72.406 27.326 1.00 70.72 6

ATOM 5373 OEl GLN D 55 49.611 72.637 28.525 .00 72.96 8

ATOM 5374 NE2 GLN D 55 48.584 73.210 26.573 .00 70.76 7

ATOM 5375 C GLN D 55 51.494 68.697 26.092 .00 51.66 6

ATOM 5376 0 GLN D 55 52.533 69.249 26.457 .00 52.73 8

ATOM 5377 N THR D 56 51.373 68.091 24.920 .00 48.75 7

ATOM 5378 CA THR D 56 52.485 68.005 23.988 ,00 48.81 6

ATOM 5379 CB THR D 56 52.769 66.534 23.617 1.00 48.35 6

ATOM 5380 OG1 THR D 56 52.793 65.733 24.801 1.00 50.12 8

ATOM 5381 CG2 THR D 56 54.101 66.408 22.925 . 00 47 . 54 6

ATOM 5382 C THR D 56 52.198 68.771 22.709 . 00 48 . 92 6

ATOM 5383 O THR D 56 51.051 68.862 22.275 1. ,00 50. .82

ATOM 5384 N THR D 57 53.243 69.320 22.101 1, ,00 48, .36

ATOM 5385 CA THR D 57 53.080 70.069 20.860 1. .00 47, .70

ATOM 5386 CB THR D 57 52.766 71.563 21.126 1. ,00 47, .89

ATOM 5387 OG1 THR D 57 51.521 71.679 21.834 1, ,00 48, .44

ATOM 5388 CG2 THR D 57 52.642 72.317 19.826 1. .00 47, .29

ATOM 5389 C THR D 57 54.322 69.988 19.995 1. .00 47, .52

ATOM 5390 O THR D 57 55.446 69.954 20.496 1. .00 48, .40

ATOM 5391 N TRP D 58 54.113 69.928 18.686 1, .00 46, .65

ATOM 5392 CA TRP D 58 55.221 69.883 17.749 1. .00 45 .92

ATOM 5393 CB TRP D 58 55.890 68.501 17.750 1 .00 46 .07

ATOM 5394 CG TRP D 58 55.055 67.379 17.192 1, .00 46 .21

ATOM 5395 CD2 TRP D 58 54.099 66.585 17.904 1, .00 45, .21

ATOM 5396 CE2 TRP D 58 53.517 65.702 16.976 1, .00 45, .14

ATOM 5397 CE3 TRP D 58 53.675 66.537 19.240 1. .00 44. ,92 6

ATOM 5398 CDl TRP D 58 55.018 66.952 15.902 1, .00 44, .73 6

ATOM 5399 NEl TRP D 58 54.097 65.945 15.761 1 .00 46, .01 7

ATOM 5400 CZ2 TRP D 58 52.533 64.783 17.336 1 .00 46 .24 6

ATOM 5401 CZ3 TRP D 58 52.696 65.618 19.596 1 .00 45 .62 6

ATOM 5402 CH2 TRP D 58 52.138 64.755 18.646 1, .00 45, .70 6

ATOM 5403 C TRP D 58 54.679 70.236 16.386 1, .00 47, .55 6

ATOM 5404 O TRP D 58 53.494 70.509 16.237 1 .00 46, .55

ATOM 5405 N SER D 59 55.537 70.226 15.381 1, .00 51, .25 7

ATOM 5406 CA SER D 59 55.097 70.602 14.051 1 .00 54 .98 6

ATOM 5407 CB SER D 59 55.688 71.974 13.705 1 .00 56 .59 6

ATOM 5408 OG SER D 59 54.969 72.610 12.659 1 .00 61, .93

ATOM 5409 C SER D 59 55.457 69.592 12.967 1 .00 55, .53

ATOM 5410 O SER D 59 56.587 69.119 12.889 1 .00 54, .93

ATOM 5411 N ASP D 60 54.479 69.279 12.126 1 .00 57, .49 7

ATOM 5412 CA ASP D 60 54.660 68.338 11.028 1 .00 59 .17 6

ATOM 5413 CB ASP D 60 53.898 67.046 11.316 1 .00 61 .53 6

ATOM 5414 CG ASP D 60 54.141 65.967 10.275 1 . 00 63 . 57

ATOM 5415 ODl ASP D 60 54.465 66.300 9.120 1 . 00 64 . 52

ATOM 5416 OD2 ASP D 60 53.988 64.773 10.611 1 . 00 64 . 89

ATOM 5417 C ASP D 60 54.067 69.020 9.811 1 . 00 60 . 52

ATOM 5418 O ASP D 60 52.847 69.016 9.615 1 . 00 59 . 95 ATOM 5419 N ARG D 61 54.,937 69..609 8.,995 1.00 62..50 7

ATOM 5420 CA ARG D 61 54. 503 70. ,334 7. ,800 1. 00 64. ,61 6

ATOM 5421 CB ARG D 61 55. 672 71. ,137 7. ,205 1. 00 67. ,57 6

ATOM 5422 CG ARG D 61 56. 000 72. .468 7. ,909 1. 00 73. ,40 6

ATOM 5423 CD ARG D 61 56. 968 73. ,283 7. ,037 1. 00 81. ,08 6

ATOM 5424 NE ARG D 61 57. ,268 74. .635 7. .537 1. ,00 86. ,56 7

ATOM 5425 CZ ARG D 61 58. ,057 75, ,522 6. .910 1. ,00 87. .41 6

ATOM 5426 NHl ARG D 61 58. ,642 75. .210 5. .749 1. ,00 87. ,01 7

ATOM 5427 NH2 ARG D 61 58. ,246 76. .731 7. .433 1. ,00 87. .16 7

ATOM 5428 C ARG D 61 53. ,867 69. .476 6. ,703 1. ,00 64. ,15 6

ATOM 5429 O ARG D 61 53. .145 69. .998 5. .844 1. ,00 63, ,51 8

ATOM 5430 N THR D 62 54, ,121 68. .170 6. ,722 1. 00 62. ,13 7

ATOM 5431 CA THR D 62 53. ,542 67. .303 5, .704 1. ,00 61. .28 6

ATOM 5432 CB THR D 62 54. .171 65. ,886 5, .716 1. ,00 62. .74 6

ATOM 5433 OG1 THR D 62 53. .809 65. ,201 6. .924 1. ,00 65, ,20 8

ATOM 5434 CG2 THR D 62 55. .692 65. .974 5. .624 1. ,00 63. ,05 6

ATOM 5435 C THR D 62 52. ,030 67. .184 5, ,911 1. ,00 60. .41 6

ATOM 5436 O THR D 62 51. .313 66, .619 5, .073 1. ,00 60. .16 8

ATOM 5437 N LEU D 63 51. .551 67. .731 7. .025 1. ,00 59. ,01 7

ATOM 5438 CA LEU D 63 50, .124 67. .705 7. .356 1, ,00 57, .25 6

ATOM 5439 CB LEU D 63 49. ,932 67. .483 8, ,860 1. ,00 55, ,13 6

ATOM 5440 CG LEU D 63 50. .567 66, .242 9. ,489 1. .00 54, .37 6

ATOM 5441 CDl LEU D 63 50. .396 66, .277 10, .997 1. .00 51, .58 6

ATOM 5442 CD2 LEU D 63 49. .917 65. .002 8. .903 1, ,00 55. .32 6

ATOM 5443 C LEU D 63 49. ,446 69. ,017 6. .973 1. ,00 56. .83 6

ATOM 5444 O LEU D 63 48, .228 69, ,091 6, .904 1. ,00 55, .62 8

ATOM 5445 N ALA D 64 50. .241 70, .052 6, .730 1. ,00 56, .52 7

ATOM 5446 CA ALA D 64 49, .702 71. ,362 6, ,388 1. ,00 56. .94 6

ATOM 5447 CB ALA D 64 50. .843 72. .351 6, .196 1. ,00 56, .75 6

ATOM 5448 C ALA D 64 48. .825 71, ,336 5, .147 1. .00 57, .08 6

ATOM 5449 O ALA D 64 49. .091 70. ,571 4. .222 1. .00 59, .16 8

ATOM 5450 N TRP D 65 47, .785 72, .174 5. .138 1. .00 56, .39 7

ATOM 5451 CA TRP D 65 46, .853 72, .286 4, .008 1. ,00 57. .81 6

ATOM 5452 CB TRP D 65 45 .718 71 .279 4, .183 1, .00 52, .06 6

ATOM 5453 CG TRP D 65 44. .662 71, .708 5, .139 1, .00 49. ,69 6

ATOM 5454 CD2 TRP D 65 44, .574 71, .383 6, .532 1. .00 48, .62 6

ATOM 5455 CE2 TRP D 65 43 .386 71, .974 7, ,027 1. .00 50, .58 6

ATOM 5456 CE3 TRP D 65 45 .379 70, .649 7, .409 1. .00 45, .78 6

ATOM 5457 CDl TRP D 65 43 .563 72, .466 4, .855 1 .00 51, .37 6

ATOM 5458 NEl TRP D 65 42 .787 72, .631 5. .985 1, .00 51, .62 7

ATOM 5459 CZ2 TRP D ^■65 42 .987 71 .849 8, .358 1 .00 48 .81 6

ATOM 5460 CZ3 TRP D 65 44 .983 70, .525 8, .731 1, .00 45. .33 6

ATOM 5461 CH2 TRP D 65 43 .797 71, .122 9. .193 1, .00 48, .88 6

ATOM 5462 C TRP D 65 46 .281 73, .723 3, .873 1, .00 60, .73 6

ATOM 5463 O TRP D 65 46 .309 74, .493 4, .839 1, .00 61, .78 8

ATOM 5464 N ASN D 66 45 .757 74, .081 2 .692 1 .00 63 .62 7

ATOM 5465 CA ASN D 66 45 .198 75, .423 2. .474 1, .00 66, .29 6

ATOM 5466 CB ASN D 66 4 .996 75 .702 0, .975 1, .00 67, .13 6

ATOM 5467 CG ASN D 66 4 .462 77 .129 0 .700 1 .00 70 .42 6

ATOM 5468 ODl ASN D 66 44 .317 77 .560 -0 .465 1 .00 68 .84 8

ATOM 5469 ND2 ASN D 66 44 .167 77, .866 1, .780 1, .00 71, .49 7

ATOM 5470 C ASN D 66 43 .886 75, .676 3, .221 1, .00 67, .74 6

ATOM 5471 O ASN D 66 42 .823 75 .208 2 .820 1 .00 67 .77 8

ATOM 5472 N SER D 67 43 .982 76 .466 4 .289 1 .00 70 .41 7

ATOM 5473 CA SER D 67 42 .852 76 .810 5, .156 1 .00 72 .51 6

ATOM 5474 CB SER D 67 43 .363 77, .028 6, .586 1, .00 71, .50 6

ATOM 5475 OG SER D 67 42 .519 7 .911 7 .324 1 .00 70 .60 8

ATOM 5476 C SER D 67 42 .021 78, .025 4 .763 1 .00 74, .90 6

ATOM 5477 O SER D 67 41 .148 78, .434 5, .530 1, .00 75, .98 8

ATOM 5478 N SER D 68 42 .272 78 .603 3. .589 1 .00 77 .57 7

ATOM 5479 CA SER D 68 41 .538 79 .805 3 .157 1 .00 79 .08 6 ATOM 5480 CB SER D 68 41,.991 80.,243 1..761 1.00 78..86 6

ATOM 5481 OG SER D 68 41. ,612 79. ,297 0. .776 1. 00 79. .93 8

ATOM 5482 C SER D 68 40. .012 79. ,707 3. ,157 1. 00 80. .32 6

ATOM 5483 O SER D 68 39. ,328 80. ,655 3. ,552 1. 00 81. ,34 8

ATOM 5484 N HIS D 69 39. .471 78. ,578 2. ,711 1. 00 80. ,85 7

ATOM 5485 CA HIS D 69 38. ,027 78. ,421 2. ,663 1. 00 81. ,81 6

ATOM 5486 CB HIS D 69 37. .562 78. ,625 1. ,239 1. ,00 84, .77 6

ATOM 5487 CG HIS D 69 37. .857 79, .994 0, .729 1. ,00 88, .72 6

ATOM 5488 CD2 HIS D 69 38. ,776 80, ,436 -0. .166 1. 00 89. ,11 6

ATOM 5489 NDl HIS D 69 37. .226 81, .117 1. .227 1. 00 88. .96 7

ATOM 5490 CEl HIS D 69 37. ,748 82, .193 0. ,660 1. 00 90. ,17 6

ATOM 5491 NE2 HIS D 69 38. ,691 81. .809 -0. ,188 1. 00 89. .66 7

ATOM 5492 C HIS D 69 37, .607 77, .066 3, .176 1. ,00 81, ,57 6

ATOM 5493 O HIS D 69 36, .624 76, .459 2, .713 1. ,00 80, .65 8

ATOM 5494 N SER D 70 38, .362 76, .606 4, .162 1. ,00 80, .66 7

ATOM 5495 CA SER D 70 38. .110 75, .319 4, .770 1. ,00 79. .33 6

ATOM 5496 CB SER D 70 38 .813 74, .240 3. .941 1. ,00 79. .59 6

ATOM 5497 OG SER D 70 40. .110 74, .675 3. ,550 1. . 00 79. ,40 8

ATOM 5498 C SER D 70 38, .624 75, .348 6. .211 1. ,00 77. .66 6

ATOM 5499 O SER D 70 39 .520 76, .135 6, .545 1. .00 76, .61 8

ATOM 5500 N PRO D 71 38, .037 74, .514 7, .088 1. ,00 76. .20 7

ATOM 5501 CD PRO D 71 36. .862 73, .660 6. .801 1, ,00 76. .18 6

ATOM 5502 CA PRO D 71 38. .420 74, .425 8, .502 1, ,00 74, .80 6

ATOM 5503 CB PRO D 71 37 .788 73 .101 8, .935 1. .00 75, .09 6

ATOM 5504 CG PRO D 71 36. .454 73 .145 8 .196 1. .00 75, .33 6

ATOM 5505 C PRO D 71 39, .933 74, .465 8. .704 1. ,00 73, .25 6

ATOM 5506 O PRO D 71 40, .685 73 .855 7 .939 1. .00 73, .92 8

ATOM 5507 N ASP D 72 40. .369 75, .180 9, .738 1. ,00 71, .15 7

ATOM 5508 CA ASP D 72 41. .794 75, .329 10, .033 1. ,00 69. .88 6

ATOM 5509 CB ASP D 72 42, .077 76 .680 10 .721 1. ,00 74, .59 6

ATOM 5510 CG ASP D 72 40 .874 77 .647 10, .691 1. ,00 79. .11 6

ATOM 5511 ODl ASP D 72 41, .131 78 .882 10 .737 1. ,00 79, .05 8

ATOM 5512 OD2 ASP D 72 39 .692 77 .190 10 .635 1. .00 80 .55 8

ATOM 5513 C ASP D 72 42, .330 74 .212 10 .923 1. .00 67, .26 6

ATOM 5514 O ASP D 72 43, .540 73, .973 10, .975 1. ,00 66. .51 8

ATOM 5515 N GLN D 73 41 .421 73 .556 11 .637 1. .00 63 .43 7

ATOM 5516 CA GLN D 73 41 .756 72 .462 12 .539 1. ,00 60 .99 6

ATOM 5517 CB GLN D 73 41 .653 72 .909 13, .981 1. ,00 63. .13 6

ATOM 5518 CG GLN D 73 42 .774 73 .723 14 .533 1, ,00 65, .58 6

ATOM 5519 CD GLN D 73 42, .460 74, .099 15, .957 1, ,00 67, .92 6

ATOM 5520 OEl GLN D 73 41, .413 74, .692 16, .216 1, .00 70 .47 8

ATOM 5521 NE2 GLN D 73 43 .338 73 .737 16 .895 1, .00 69 .20 7

ATOM 5522 C GLN D 73 40 .810 71 .287 12 .397 1 .00 58 .94 6

ATOM 5523 0 GLN D 73 39 .639 71 .445 12 .029 1, .00 59 .19 8

ATOM 5524 N VAL D 74 41 .317 70 .108 12 .737 1. .00 56, .36 7

ATOM 5525 CA VAL D 74 40 .531 68 .883 12 .698 1, .00 52 .71 6

ATOM 5526 CB VAL D 74 40, .635 68 .177 11 .329 1. .00 51, .38 6

ATOM 5527 CGI VAL D 74 39 .944 68 .998 10 .260 1. .00 48 .73 6

ATOM 5528 CG2 VAL D 74 42 .087 67 .951 10 .973 1 .00 48 .36 6

ATOM 5529 C VAL D 74 41 .089 67 .959 13 .760 1 .00 50 .70 6

ATOM 5530 O VAL D 74 42 .240 68 .108 14 .173 1, .00 49 .32 8

ATOM 5531 N SER D 75 40 .264 67 .023 14 .215 1, .00 48, .60 7

ATOM 5532 CA SER D 75 40 .696 66 .051 15 .206 1 .00 46 .92 6

ATOM 5533 CB SER D 75 39 .555 65 .729 16 .166 1 .00 48 .45 6

ATOM 5534 OG SER D 75 39 .444 66 .718 17 .168 1 .00 48 .28 8

ATOM 5535 C SER D 75 41 .159 64 .789 14 .487 1 .00 44 .70 6

ATOM 5536 O SER D 75 40 .397 64 .143 13 .781 1 .00 43 .70 8

ATOM 5537 N VAL D 76 42 .424 64 .449 14 .675 1 .00 44 .00 7

ATOM 5538 CA VAL D 76 43 .024 63 .281 14 .039 1 .00 43 .43 6

ATOM 5539 CB VAL D 76 44 .283 63 .687 13 .264 1 .00 44 .79 6

ATOM 5540 CGI VAL D 76 44 .891 62 .486 12 .604 1 .00 43 .63 6 -v

ATOM 5541 CG2 VAL D 76 43. ,943 64. ,746 12, ,241 1. ,00 42. 10 6

ATOM 5542 C VAL D 76 43. 419 62. 193 15. 034 1. 00 43. 50 6

ATOM 5543 O VAL D 76 44. 004 62. 472 16. 078 1. 00 45. 44 8

ATOM 5544 N PRO D 77 43. ,102 60. 929 14. 721 1. 00 42. 76 7

ATOM 5545 CD PRO D 77 42. ,235 60. ,402 13. ,656 1. 00 41. 52 6

ATOM 5546 CA PRO D 77 43. ,472 59. ,865 15. .650 1. ,00 41. ,41 6

ATOM 5547 CB PRO D 77 42. ,856 58. ,628 15. ,009 1. ,00 42. ,36 6

ATOM 5548 CG PRO D 77 41. .674 59. .168 14. .296 1. ,00 40. .67 6

ATOM 5549 C PRO D 77 44. ,985 59. .774 15. ,749 1. 00 40. 15 6

ATOM 5550 O PRO D 77 45. ,687 59, .922 14, ,762 1. ,00 39. ,02 8

ATOM 5551 N ILE D 78 45. .474 59. .537 16. ,954 1. ,00 41. ,66 7

ATOM 5552 CA ILE D 78 46. 899 59. .421 17. 217 1. 00 42. 23 6

ATOM 5553 CB ILE D 78 47. .113 59. .019 18, .687 1. ,00 43. ,04 6

ATOM 5554 CG2 ILE D 78 48. .495 58. .518 18. .924 1. ,00 45, ,01 6

ATOM 5555 CGI ILE D 78 46, .872 60, .236 19, .555 1, ,00 47, .88 6

ATOM 5556 CDl ILE D 78 47. .618 61. .461 19. ,057 1. ,00 48. .43 6

ATOM 5557 C ILE D 78 47, .591 58, .432 16, .299 1. .00 42, .53 6

ATOM 5558 0 ILE D 78 48, ,717 58. .643 15, .880 1, .00 44, ,25 8

ATOM 5559 N SER D 79 46. ,891 57. ,358 15. ,979 1. ,00 43. 93 7

ATOM 5560 CA SER D 79 47, .410 56. .302 15, .127 1. .00 43. ,22 6

ATOM 5561 CB SER D 79 46. .457 55. .110 15. .185 1. ,00 42. ,69 6

ATOM 5562 OG SER D 79 45, .130 55. .523 14, .910 1. .00 43. .59 8

ATOM 5563 C SER D 79 47, .661 56, .692 13, ,668 1. ,00 42. ,26 6

ATOM 5564 O SER D 79 48 .319 55 .953 12, .937 1. .00 41, .56 8

ATOM 5565 N SER D 80 47 .138 57, .835 13. .243 1. .00 39, .86 7

ATOM 5566 CA SER D 80 47. .326 58. .282 11, ,871 1. ,00 40. ,25 6

ATOM 5567 CB SER D 80 46 .026 58 .840 11, .307 1, .00 40, .77 6

ATOM 5568 OG SER D 80 45. .025 57. .845 11. ,259 1. ,00 48. ,70 8

ATOM 5569 C SER D 80 48. .413 59 .342 11, .742 1, .00 41. .01 6

ATOM 5570 O SER D 80 48 .658 59, .842 10, .655 1, .00 41, .05 8

ATOM 5571 N LEU D 81 49 .067 59 .671 12 .847 1. .00 39, .67 7

ATOM 5572 CA LEU D 81 50 .112 60 .678 12 .844 1 .00 39, .96 6

ATOM 5573 CB LEU D 81 49, .703 61. .886 13. .684 1. .00 40, .31 6

ATOM 5574 CG LEU D 81 48 .371 62 .571 13, .448 1 .00 42 .96 6

ATOM 5575 CDl LEU D 81 48, .019 63, .429 14, .638 1. .00 41. .75 6

ATOM 5576 CD2 LEU D 81 48 .454 63 .382 12 .191 1 .00 44 .21 6

ATOM 5577 C LEU D 81 51 .357 60, .109 13, .472 1, .00 38, .80 6

ATOM 5578 O LEU D 81 51 .303 59 .077 1 .119 1 .00 39 .28 8

ATOM 5579 N TRP D 82 52 .478 60 .795 1 .276 1 .00 37 .55 7

ATOM 5580 CA TRP D 82 53, .726 60, .398 13. .891 1. .00 36, .02 6

ATOM 5581 CB TRP D 82 54 .927 60 , .981 13. .158 1, .00 39, .06 6

ATOM 5582 CG TRP D 82 56, .206 60 .891 13. .958 1, .00 40, ,02 6

ATOM 5583 CD2 TRP D 82 56 .715 61 .864 1 .887 1 .00 39 .10 6

ATOM 5584 CΞ2 TRP D 82 57, .87.8 61, .318 15, .463 1, .00 38, .66 6

ATOM 5585 CE3 TRP D 82 56 .294 63 .140 15 .292 1 .00 38 .90 6

ATOM 5586 CDl TRP D 82 57 .060 59 .840 14 .007 1 .00 40 .23 6

ATOM 5587 NEl TRP D 82 58 .065 60, .082 14. .908 1, .00 40, .21 7

ATOM 5588 CZ2 TRP D 82 58 .630 61 .997 16 .422 1 .00 36 .80 6

ATOM 5589 CZ3 TRP D 82 57 .038 63 .812 16, .247 1 .00 40, .18 6

ATOM 5590 CH2 TRP D 82 58 .195 63 .238 16 .801 1 .00 38 .54 ^•6

ATOM 5591 C TRP D 82 53 .606 61, .068 15, .236 1, .00 35, .47 6

ATOM 5592 O TRP D 82 53 .085 62 .172 15 .339 1 .00 36 .72 8

ATOM 5593 N VAL D 83 54 .078 60 .408 16 .272 1 .00 34 .62 7

ATOM 5594 CA VAL D 83 53 .996 60 .989 17 .592 1 .00 36 .17 6

ATOM 5595 CB VAL D 83 52 .827 60 .341 18 .381 1 .00 35 .89 6

ATOM 5596 CGI VAL D 83 52 .906 60 .676 19 .835 1 .00 38 .30 6

ATOM 5597 CG2 VAL D 83 51 .507 60 .840 17 .832 1 .00 35 .92 6

ATOM 5598 C VAL D 83 55 .335 60 .810 18 .312 1 .00 37 .27 6

ATOM 5599 O VAL D 83 56 .035 59 .821 18 .113 1 .00 36 .95 8

ATOM 5600 N PRO D 84 55 .727 61 .796 19 .125 1 .00 35 .49 7

ATOM 5601 CD PRO D 84 55 .073 63 .095 19 .324 1 .00 37 .20 6 CD cn en -is- ^ oo oo IV) ιv> O en o eπ o cn o en o cn o en to to to toto to toto toto to toto to to to to to to to β ^ β β ι^ ι-3 ι-3 β B β tβ 3 >-3 >^ >-3 H3 β 3 '-3 β β β μ3 3 β β ι-3 3 ^ ι-3 ι-3 β !-3 ι-3 ^

O O O O O Ω O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O Q O O O O O O Q Q

Ul Ul (Jl ϋl l)l lI10l W (Λ cn

_Jι ω w ω ω _ M - - -θ t M t ω _ Ω aO aOΩgO Ω a Ω O Ω Ω Ω Ω Ω Ω Ω Ω a O Ω Ω Ω a O O Ω Ω a O Ω Ω Ω Ω Ω Ω a O Ω O O Ω Ω Ω a O Ω Ω Ω

Ω Ώ ω α K N tS O tT ϋ Ω ω ^ ω > α α Ω ω ; U O Q B > Ω ω μ-» to ω ; toα pΩ ft) ^ t to p p to μ-> to H

H H H H H !P' i_=' i_=' !-=' ' ' ' ; ' f-3 '-3 β ι-3 β 3 - β _ ι-3 _ β _ ι-3 - ι- _ ι- l_^ρ' l_ι=^, S=^| ϊfc' S=^, |w ' ' lr^l tr¹ tr¹ f tr¹ tr¹ iA lr^, |f |_=' ' |_ ^' |f ^tτ) ^fα iti ^|_ι i

- - c-- - -- c- -__- t-- ω-- c-o- Kι~i; KJ ι^ κi | ι-< κ; ι<; κ; κ; «J __r^, __H __H __ __ __-' f___ p_ f_ f_ t_ t_ M t_ K t_ t- t __: w co co ω co co co co pd pd ?d pd

M H M M M ^ ^ ^ ^ ^ a a a a a a d d pα pd ?d fd fd ^⁾ d pd ' ' ' ' ! ^, ' ^■ ' C -j^■ α α cj ci Q q C ^jj . . _ tl . . H1 . 0 0 0 0 α α α α o α tj σ α o α α σ α α α o σ o o o σ D o σ α D σ o o D O D σ α σ

SO SO SO SO Lo ω LO LO O lil lO lO sO SO sO SO sD SO CO CO CK OO CO CXI ∞ OO OO CO OO CO OO OO CO ∞ to t>J ts_) io to μ^j μ^j μ-^s μ-' μ-' o o o o o o o o so so so so so Lo so ι__! so ι_D So Lo cD oo oo oo oo ~j ~ - ~j o

_n w iΛ ϋi uι σι uι ι_i -i t_ι w -θ U3

∞ π ∞ tso

~ u uι uι ui ϋi (_ι _Ji (_π uι _jι t_ι uι σι σι ϋi ω ϋi ui uι uι oι <3i uι uπ m oι ι_ι W Ln w t_ι ui -n ui -n Lπ Ui iΛ Ui t_ι uι m M co ω tθ ιP- L ιi__> cn w-\ w-ι σι cn o σ so _o -o -J c -J μ-' σ so so μJ σ LD so c» cxι -j oo s o ∞

W CO P lD t tD 0100 Ul ~l CD o ι_ m ω u ιi) ⁾ ^ o ui ϋι o o uι w o p i)3 M ω -J - oι ~i so tj - _ t μ ~i (Λ ιi!. ι α) ^ ιo t. tιJ to m (_i vi μ uι ω o ω oi m ω to oi o p to oi o αi ~j ~θ o t>o σι i_3 ι θ ι)^ -π crι o c ~J » ___π o t π ιi^ o Lθ ιi__. so _rι ~J o σι _ o w -o o n o t co Lo o i cxi i.n μ-¹ μ o . ω o3 t o ω μ J so o ω p u o p m ιo ~ι ^ ^ ^ ω oι ^ μ ω -4 uι ~ι iD θ P _5, o uj _ m ω p _ . cD ~i -θ o ^ it_. L _O L _O L LO L Lo L LO Lw LO L L L LO L LO L CO t>J tO LO LO LJ 0 1_3 SO -J ~J Lπ _ ιI-» Ln Lπ ~J m CO OΛ -0 -J C^ Lπ ιt^ ιl-. OO sO SO O o μ-' M Lw CO CO tO M o __n co -J θ ~J t-^, w cΛ Lπ -~J c ~J _n Lπ _n _P^ I-^> Lπ w o co co Lπ .ρ~ σι ~J o so .^

L_j ~j L_j ω co μ-» Lπ cn L cn ι__> αϊ o μ-^ι cn o ~J ~J o -J _.ι^ σι co o .ι^ crι o ω to t <__> ω ι~ .~j o o o -θ uι ι_-> -θ Ji μ-> π o μ-^{l (}jθ _p cD θ _o io so H> H μ-s ι-^» μ-^ι μ^{i j} ι-^ι -' μ^j μⁱ μⁱ Pⁱ i^ ι-ⁱ i^j ι-^ι μ^{ι j} μ^j μ-^ι ι-ⁱ μ^j μ^ μ^j ι^j i-> μ-^l μ-^> μ^J μ-^j μ-> μ-^ι μ-> μ-^l μ-> _-> μ-^> _-¹ μ μ μ ooo ooooooσooo oσooσooooo oo ooo ooooo oσ oooooooooα ooooooooooooo oo oooo oooooooooσooo ooooo oo oo ooσoooooooooooooo DOo oooooooooooo

L_n ιl-ι .l-» >l-> ιt-> .P-- _l-> _I-. .t-. __i so oo ₁fi ι)-. μ-^s t t co to to to ∞

L Lπ o μ-> o -J ∞ co Lπ o ω -j ω o M Co so t_o t_π cn ι^ sD σι Lϋ tNJ i_o ∞ Lπ oo ~j o co ~ ∞ ~ Lπ ιl^ Ln oo o _!^ cΛ ~J ιl^ so cn l-¹ o o ~J Lo so ι-' Lπ t o l_o oo ιf^ μ-' ~ Lπ o oo ιi-. co μ-^l o σι to o cn

ATOM 5663 CDl ILE D 92 57.,559 52.,447 41.,544 1.00 57.,95 6

ATOM 5664 C ILE D 92 55. 921 51. ,998 37. ,180 1. 00 43. ,63 6

ATOM 5665 O ILE D 92 55. 867 50. 816 37. 502 1. 00 43. ,77 8

ATOM 5666 N SER D 93 55, ,051 52. ,546 36. ,343 1. 00 41, ,02 7

ATOM 5667 CA SER D 93 53. 968 51. 788 35. ,733 1. 00 39. ,43 6

ATOM 5668 CB SER D 93 52. .673 51. .994 36. .498 1. ,00 40, ,39 6

ATOM 5669 OG SER D 93 52. ,200 53. ,324 36. ,320 1. ,00 40, .98 8

ATOM 5670 C SER D 93 53. ,802 52. ,387 34. ,366 1. ,00 39. .82 6

ATOM 5671 O SER D 93 54. .349 53. ,452 34. .103 1. 00 38, ,78 8

ATOM 5672 N LYS D 94 53. ,063 51. 727 33. ,484 1. 00 40. ,02 7

ATOM 5673 CA LYS D 94 52. ,883 52. ,322 32. .173 1. 00 42. .68 6

ATOM 5674 CB LYS D 94 52. ,695 51, .260 31. .081 1, ,00 42 .12 6

ATOM 5675 CG LYS D 94 51. .789 50, ,113 31. .405 1. ,00 45, .31 6

ATOM 5676 CD LYS D 94 51, .980 48. .999 30, .378 1. ,00 48, .12 6

ATOM 5677 CE LYS D 94 51, .973 49. ,545 28, .957 1. ,00 49, .66 6

ATOM 5678 NZ LYS D 94 52, ,092 48. .466 27, .938 1. ,00 53, .06 7

ATOM 5679 C LYS D 94 51, .738 53, ,319 32. .205 1. ,00 42, .30 6

ATOM 5680 O LYS D 94 50, .899 53, .299 33, .104 1. ,00 42, .15 8

ATOM 5681 N PRO D 95 51, .707 54. .230 31, .234 1. ,00 41 .20 7

ATOM 5682 CD PRO D 95 52, .637 54, ,379 30, .108 1. ,00 37, .85 6

ATOM 5683 CA PRO D 95 50, .655 55, .243 31, .178 1. ,00 40 .86 6

ATOM 5684 CB PRO D 95 51, .064 56. .117 29, .990 1. .00 41 .55 6

ATOM 5685 CG PRO D 95 52, .512 55. .834 29, .821 1. .00 42, .69 6

ATOM 5686 C PRO D 95 49, .263 54. ,691 30, .981 1. .00 39 .96 6

ATOM 5687 O PRO D 95 49 .030 53. .893 30 .080 1, .00 39 .70 8

ATOM 5688 N GLU D 96 48, .344 55. .113 31, .835 1. ,00 40, .14 7

ATOM 5689 CA GLU D 96 46, .961 54. ,718 31, .689 1. .00 38, .41 6

ATOM 5690 CB GLU D 96 46, .321 54, ,399 33, .041 1. .00 40, .63 6

ATOM 5691 CG GLU D 96 44, .880 53. .856 32, .923 1. ,00 48, .74 6

ATOM 5692 CD GLU D 96 44 .232 53. .503 34 .273 1. .00 51 .27 6

ATOM 5693 OEl GLU D 96 44, .983 53. .350 35. .261 1. ,00 50, .19 8

ATOM 5694 OΞ2 GLU D 96 42 .979 53, .360 34 .345 1. .00 50 .07 8

ATOM 5695 C GLU D 96 46 .324 55 .963 31 .084 1. ,00 37 .34 6

ATOM 5696 O GLU D 96 45 .998 56, .900 31 .799 1. ,00 36, .63 8

ATOM 5697 N VAL D 97 46 .199 55, .988 29, .760 1, ,00 34 .71 7

ATOM 5698 CA VAL D 97 45 .599 57 .120 29 .079 1 .00 32 .69 6

ATOM 5699 CB VAL D 97 45 .881 57, .066 27, .582 1. .00 30 .58 6

ATOM 5700 CGI VAL D 97 45 .289 58 .260 26 .896 1, ,00 30 .36 6

ATOM 5701 CG2 VAL D 97 47 .361 57, .037 27 .354 1, .00 28 .89 6

ATOM 5702 C VAL D 97 44 .104 57, .067 29, .345 1. .00 34 .47 6

ATOM 5703 O VAL D 97 43 .431 56, .124 28 .962 1, .00 35 .88 8

ATOM 5704 N LEU D 98 43 .597 58 .091 30 .019 1. .00 35 .68 7

ATOM 5705 CA LEU D 98 42 .190 58 .174 30 .401 1 .00 36 .36 6

ATOM 5706 CB LEU D 98 42 .071 58 .943 31 .713 1, .00 35 .92 6

ATOM 5707 CG LEU D 98 42 .941 58, .547 32, .894 1, .00 36, .85 6

ATOM 5708 CDl LEU D 98 42 .906 59, .639 33 .914 1. .00 35 .58 6

ATOM 5709 CD2 LEU D 98 42 .456 57 .261 33 .487 1, .00 39 .84 6

ATOM 5710 C LEU D 98 41 .276 58 .845 29 .386 1 .00 38 .24 6

ATOM 5711 O LEU D 98 40 .055 58 .850 29 .549 1, .00 37 .04 8

ATOM 5712 N THR D 99 41 .862 59 .409 28 .338 1 .00 37 .00 7

ATOM 5713 CA THR D 99 41 .082 60 .130 27 .344 1, .00 36 .28 6

ATOM 5714 CB THR D 99 41 .449 61 .644 27 .378 1, .00 36 .19 6

ATOM 5715 OG1 THR D 99 42 .863 61 .803 27 .177 1 .00 38 .29 8

ATOM 5716 CG2 THR D 99 41 .075 62 .248 28 .706 1 .00 31 .31 6

ATOM 5717 C THR D 99 41 .224 59 .629 25 .910 1 .00 35 .89 6

ATOM 5718 O THR D 99 42 .148 58 .883 25 .588 1, .00 35 .45 8

ATOM 5719 N PRO D 100 40 .281 60 .026 25 .034 1 .00 34 .88 7

ATOM 5720 CD PRO D 100 39 .043 60 .761 25 .337 1, .00 35 .25 6

ATOM 5721 CA PRO D 100 40 .303 59 .630 23 .631 1 .00 33 .36 6

ATOM 5722 CB PRO D 100 39 .217 60 .492 23 .024 1 .00 32 .41 6

ATOM 5723 CG PRO D 100 38 .223 60 .527 24 .093 1 .00 33 .73 6 ATOM 5724 C PRO D 100 41,.666 59,.955 23,.077 1.,00 35..04 6

ATOM 5725 O PRO D 100 42, .188 61. ,028 23. ,310 1. 00 36. ,02 8

ATOM 5726 N GLN D 101 42. .256 59. ,026 22. .350 1. 00 38. ,56 7

ATOM 5727 CA GLN D 101 43. .574 59, .280 21. .817 1. ,00 39. .66 6

ATOM 5728 CB GLN D 101 44. ,356 57. .980 21. ,749 1. 00 38. .98 6

ATOM 5729 CG GLN D 101 44. ,890 57, .613 23. .109 1. 00 41. ,80 6

ATOM 5730 CD GLN D 101 45. .318 56, .175 23. .201 1. ,00 46, .38 6

ATOM 5731 OEl GLN D 101 46. .158 55 .714 22, .439 1. .00 50, .42 8

ATOM 5732 NE2 GLN D 101 44. .735 55. .447 24, ,143 1. ,00 49. .13 7

ATOM 5733 C GLN D 101 43. .543 59. .994 20, ,486 1. ,00 39. .27 6

ATOM 5734 O GLN D 101 43. .965 59. .463 19, ,463 1. ,00 38, .19 8

ATOM 5735 N LEU D 102 43. .037 61, .224 20. .540 1. ,00 .40. .46 7

ATOM 5736 CA LEU D 102 42, .910 62, .103 19, .381 1. .00 40. .51 6

ATOM 5737 CB LEU D 102 41. .467 62. .590 19, .231 1. .00 37, .39 6

ATOM 5738 CG LEU D 102 40. .382 61, .515 19, .121 1. ,00 38, .97 6

ATOM 5739 CDl LEU D 102 39. .030 62, .182 18, .988 1, ,00 36, .48 6

ATOM 5740 CD2 LEU D 102 40. .657 60, .628 17, .925 1, .00 36, .34 6

ATOM 5741 C LEU D 102 43, .804 63, .308 19, ,554 1, ,00 41, .42 6

ATOM 5742 O LEU D 102 43. .990 63. .794 20. ,665 1, ,00 43. ,09 8

ATOM 5743 N ALA D 103 44 .375 63 .777 18, .455 1, ,00 40 .44 7

ATOM 5744 CA ALA D 103 45 .221 64 .953 18, .489 1, .00 40, .53 6

ATOM 5745 CB ALA D 103 46 .549 64 .673 17 .847 1, .00 43 .43 6

ATOM 5746 C ALA D 103 44 .500 66 .050 17, .731 1, .00 41 .82 6

ATOM 5747 O ALA D 103 43. .503 65, .803 17, ,058 1, ,00 41, .33 8

ATOM 5748 N ARG D 104 44. .998 67 .271 17, .849 1, .00 42, .58 7

ATOM 5749 CA ARG D 104 44 .369 68, .381 17, .165 1. .00 43, .20 6

ATOM 5750 CB ARG D 104 43, .995 69, .450 18, .183 1. .00 43, .57 6

ATOM 5751 CG ARG D 104 43. .032 70, .480 17, .678 1. .00 40, .98 6

ATOM 5752 CD ARG D 104 41 .674 69 .900 17 .425 1, .00 39 .96 6

ATOM 5753 NE ARG D 104 40 .803 70 .951 16 .909 1, .00 41 .32 7

ATOM 5754 CZ ARG D 104 39 .517 70, .802 16, .635 1. .00 39. .52 6

ATOM 5755 NHl ARG D 104 38. .927 69, .633 16, .824 1. ,00 40, ,96 7

ATOM 5756 NH2 ARG D 104 38. .826 71 .832 16. .175 1. ,00 38 .44 7

ATOM 5757 C ARG D 104 45 .380 68 .896 16, .162 1. ,00 43, .89 6

ATOM 5758 O ARG D 104 46 .508 69 .192 16, .526 1, .00 44, .97 8

ATOM 5759 N VAL D 105 4 .989 68 .966 14 .894 1, .00 44 .88 7

ATOM 5760 CA VAL D 105 45, .910 69, .427 13, .863 1, .00 46, .87 6

ATOM 5761 CB VAL D 105 46, .094 68. .380 12, .751 1, .00 44, .91 6

ATOM 5762 CGI VAL D 105 47 .165 68 .838 11 .787 1, .00 42 .60 6

ATOM 5763 CG2 VAL D 105 46, .469 ^'67. .050 13. .346 1. .00 43, ,58 6

ATOM 5764 C VAL D 105 45. .467 70. ,729 13, .223 1, .00 48. ,29 6

ATOM 5765 O VAL D 105 44 .335 70 .845 12, .731 1, .00 47 .85 8

ATOM 5766 N VAL D 106 46 .375 71 .702 13 .238 1 .00 48 .47 7

ATOM 5767 CA VAL D 106 46, .129 73 .018 12 .663 1. .00 50. .73 6

ATOM 5768 CB VAL D 106 46 .855 74 .106 13. .472 1, .00 50. .55 6

ATOM 5769 CGI VAL D 106 46 .392 75 .477 13 .026 1, .00 51 .23 6

ATOM 5770 CG2 VAL D 106 46, .601 73. .903 14, .951 1. .00 48, .01 6

ATOM 5771 C VAL D 106 46 .636 73 .025 11, .216 1, .00 51 .91 6

ATOM 5772 O VAL D 106 47, .664 72, .420 10, .918 1. .00 52, .36 8

ATOM 5773 N SER D 107 45 .920 73 .712 10 .329 1, .00 52 .06 7

ATOM 5774 CA SER D 107 46 .281 73 .761 8, .915 1, .00 51 .56 6

ATOM 5775 CB SER D 107 45 .391 74 .756 8 .185 1, .00 52, .91 6

ATOM 5776 OG SER D 107 45, .259 75 .941 8 .943 1, .00 59, .44 8

ATOM 5777 C SER D 107 47, .726 74, .058 8. .591 1. .00 50. .83 6

ATOM 5778 O SER D 107 48 .188 73 .739 7 .511 1, .00 50 .82 8

ATOM 5779 N ASP D 108 48 .451 74 .657 9 .519 1 .00 53 .72 7

ATOM 5780 CA ASP D 108 49 .853 74 .978 9 .262 1 .00 57 .12 6

ATOM 5781 CB ASP D 108 50 .239 76 .289 9 .965 1, .00 58 .24 6

ATOM 5782 CG ASP D 108 50 .271 76 .163 11 .475 1, .00 61, .04 6

ATOM 5783 ODl ASP D 108 49 .396 75 .459 12 .042 1, .00 63 .89 8

ATOM 5784 OD2 ASP D 108 51 .162 76 .782 12 .095 1 .00 60, .97 8 -1lυ/

ATOM 5785 C ASP D 108 50.827 73. ,870 9. ,665 1. 00 58. 88 6

ATOM 5786 O ASP D 108 52. ,043 74. ,071 9. ,635 1. ,00 61. ,62 8

ATOM 5787 N GLY D 109 50. .293 72. .711 10. ,051 1. ,00 58. ,94 7

ATOM 5788 CA GLY D 109 51, .134 71. .589 10. .437 1. ,00 58. .18 6

ATOM 5789 C GLY D 109 51. ,424 71. ,483 11. ,918 1. ,00 57. ,62 6

ATOM 5790 O GLY D 109 52. ,186 70. .612 12. .343 1. ,00 56. ,21 8

ATOM 5791 N GLU D 110 50. 831 72. ,370 12. ,707 1. 00 58. ,61 7

ATOM 5792 CA GLU D 110 51. ,042 72. ,345 14. ,152 1. 00 59. ,21 6

ATOM 5793 CB GLU D 110 50. ,664 73. .700 14. .776 1. ,00 62. .41 6

ATOM 5794 CG GLU D 110 51. ,327 74. ,002 16. ,134 1. 00 66 . ,58 6

ATOM 5795 CD GLU D 110 52. ,852 74. ,104 16. ,041 1. 00 69, ,79 6

ATOM 5796 OEl GLU D 110 53. ,375 74. ,340 14. ,921 1. ,00 70. .58 8

ATOM 5797 OE2 GLU D 110 53, ,527 73. .963 17, ,089 1. .00 70, .10 8

ATOM 5798 C GLU D 110 50. .158 71, .232 14. .712 1. ,00 56. .76 6

ATOM 5799 O GLU D 110 49, .001 71, ,079 14. ,320 1. ,00 54. .86 8

ATOM 5800 N VAL D 111 50. ,723 70, .451 15, .625 1. ,00 55, .23 7

ATOM 5801 CA VAL D 111 50. .013 69. .333 16. .236 1. , 00 53. ,43 6

ATOM 5802 CB VAL D 111 50, .704 67, .976 15, .889 1. ,00 53. .47 6

ATOM 5803 CGI VAL D 111 49, .934 66, .821 16, ,500 1. ,00 51. ,83 6

ATOM 5804 CG2 VAL D 111 50, .798 67, .803 14, .382 1, .00 52, .57 6

ATOM 5805 C VAL D 111 49 .962 69, .470 17 .754 1, .00 53, .05 6

ATOM 5806 O VAL D 111 50, .972 69, ,747 18, .400 1. .00 52, .81 8

ATOM 5807 N LEU D 112 48, .783 69, .269 18, .323 1, ,00 51, .91 7

ATOM 5808 CA LEU D 112 48, .631 69, .354 19. .766 1. . 00 51, ,71 6

ATOM 5809 CB LEU D 112 47 .776 70, .566 20 .155 1, ,00 55 .12 6

ATOM 5810 CG LEU D 112 47, .832 71, .901 19, .392 1. ,00 55, .82 6

ATOM 5811 CDl LEU D 112 49, .269 72, .287 19, .035 1. .00 56, .65 6

ATOM 5812 CD2 LEU D 112 46, .985 71. .777 18, .155 1. .00 55, ,54 6

ATOM 5813 C LEU D 112 47, .959 68. .089 20, .292 1. .00 51, ,46 6

ATOM 5814 O LEU D 112 46, .833 67, .769 19, .900 1. ,00 51, .33 8

ATOM 5815 N TYR D 113 48. .659 67. .365 21, .162 1, .00 48. ,43 7

ATOM 5816 CA TYR D 113 48, .128 66 .149 21, .762 1. .00 45, ,71 6

ATOM 5817 CB TYR D 113 48, .941 64, .928 21, .318 1. .00 43, .52 6

ATOM 5818 CG TYR D 113 48 .490 63 .601 21 .918 1 .00 41 .37 6

ATOM 5819 CDl .TYR D 113 47, .142 63 .255 21, .975 1, .00 39, .60 6

ATOM 5820 CEl TYR D 113 46, .735 62. .028 22. .492 1, .00 38, .43 6

ATOM 5821 CD2 TYR D 113 49, .423 62. .679 22, .397 1, .00 40, .11 6

ATOM 5822 CE2 TYR D 113 49, .028 61 .458 22, .911 1, .00 39, .17 6

ATOM 5823 CZ TYR D 113 47 .682 61 .134 22 .958 1. .00 40 .31 6

ATOM 5824 OH TYR D 113 47 .283 59 .921 23 .470 1 .00 40 .08 8

ATOM 5825 C TYR D 113 48 .218 66 .325 23 .262 1 .00 45 .22 6

ATOM 5826 O TYR D 113 49 .302 66 .442 23 .812 1 .00 44 .34 8

ATOM 5827 N MET D 114 47 .073 66 .352 23 .924 1 .00 47 .16 7

ATOM 5828 CA MET D 114 47 .-044 66 .541 25 .368 1 .00 48 .56 6

ATOM 5829 CB MET D 114 46 .457 67 . 906 25 .681 1. .00 53 .17 6

ATOM 5830 CG MET D 114 46 .536 68 .281 27 .130 1 .00 58 .47 6

ATOM 5831 SD MET D 114 45 .470 69 .687 27 .429 1 .00 64 .86 16

ATOM 5832 CE MET D 114 46 .527 70 .991 26 .840 1 .00 63 .87 6

ATOM 5833 C MET D 114 46 .214 65 .472 26 .062 1 .00 47 .72 6

ATOM 5834 0 MET D 114 45 .060 65 .705 26 .424 1 .00 47 .31 8

ATOM 5835 N PRO D 115 46 .790 64 .279 26 .251 1 .00 45 .85 7

ATOM 5836 CD PRO D 115 48 .108 63 .831 25 .761 1 .00 45 .44 6

ATOM 5837 CA PRO D 115 46 .080 63 .184 26 .903 1 .00 44 .65 6

ATOM 5838 CB PRO D 115 ^'46 .818 61 .967 26 .385 1 .00 46 .29 6

ATOM 5839 CG PRO D 115 48 .231 62 .454 26 .372 1 .00 45 .12 6

ATOM 5840 C PRO D 115 46 .159 63 .283 28 .416 1 .00 44 .40 6

ATOM 5841 O PRO D 115 47 .145 63 .787 ^'28 .954 1 .00 43 .35 8

ATOM 5842 N SER D 116 45 .124 62 .811 29 .102 1 .00 42 .71 7

ATOM 5843 CA SER D 116 45 .142 62 .828 30 .551 1 .00 40 .50 6

ATOM 5844 CB SER D 116 43 .752 62 .976 31 .110 1 .00 37 .94 6

ATOM 5845 OG SER D 116 43 .829 63 .015 32 .516 1 .00 44 .37 8 CD en en oo oo IV) ro O en o en σ en o en o en en to to to to to to to to to to ;)y to ; ;>ι >' to to to ;> ^μ3 f_ ι-3 >-3 >-3 ^ ι-3 β !-3 t^ i- ι-3 β β ^ ^ ι- β β ι-3 β tβ >-3 ι-3 β ι-3 β !-3 β β ι-3 β ι^ ^ β β

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O Q O O O Q O Q O O Q O Q O Q Q Q Q Q Q O Q O g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g s g g g g g g g g g g g g g g g g g g g s s g g ι tn _Ji uι ιι ϋι ijι uι iΛ Ui iΛ Ui uι uι ln (_n ι_i (Λ i_ι tjι ι_i (_n ι_ι tn w u ^ uι ιjι __ι (_ι tΛ Ui tΛ W so ω io so so so ω co co co oo co co oo co co ∞ co ∞ ∞ ∞ oD oo oo co co ∞ oo oo co ∞

O O O O O O O !_0 O U_> S0 SO o S sD S--> SO C0 C>0 C0 C0 CD 00 03 C0 00 03 ~J ~J ~0 -J ~J O θ Ui _^ GJ W H o ι_3 co ~ c π _l!-_> ω _o μ-' o so co ~o σ> Lπ .ρ> ω ιo O O O a OΩΩΩΩΩΩΩΩΩSOΩ Ω a Ω a O Ω a O O a a Ω O a O Ω O O O i Ώ ω > N td o Ω ω M t_ D Ω td > κ κ N t_ n ω l θ Ω Ω ta

M P M P to (-> to μ μ-¹ l-» co

O Ω Ω to m &! tD t. CQ ^,ι) 'ϋ ^lτl . 'c) _ . _ _ - ifl ^ ^l > ' S=^J Ω Ω Ω Ω Ω Ω Ω ^l ' ^l ' _ϊ^:, >' ' ' ' H H H H H H H CO H. κ| i M M W W M M ffi K !S W _B ffi ffi ffi K _i! _3. Pd d pd 5 » 5 » d pd » p ι^ P !^! P P !→ e ι^ⁱ d pd ? ?d pd p p[_^ pd d t-^, lr^, tr¹ tr¹ f tr¹ t-ⁱ t_ cn cn W pd pd pd » pd M M M M M M K M M M M Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω a a a a a a a a a Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω H αoDασαoϋϋuαϋoϋααooϋ μ^j μⁱ H μ-> μ-> μ^j μ-^s μ-> μ-^> μ^j μ^j μ^j μ-' ^j μ-^l -' μ^j μ^{j j} μ^j μ^j -> -^ι μ-^ι μ-^ι μ-> μ-^ι μ-> μ-' μ-> μ-^l H^ι μ^j μ-^l μ^ tO to t M tO tO tO -O tO lO tO W tO tJ tO M -O t IO tO tO t t -O tO tO lO M tO -O tO P P P P P P P P P P P P P P P P P P P P P P P P P P P P P ω _o _ co to co t_o tNJ t --^> μ-^l μ-¹ μ-^ι μ^j μ-' μ-^ι μ-' μ^Λ σ o o o o o o o o o c) so ~o so u? so ι_D so o sD Co co ∞

m m ui σi σi m cn ui w ϋi iji ui w σi oi ui Ui tji ui σi ^ ui iΛ W Ui ln iΛ iΛ Lπ ui w ui ui iii ui ui -i ui ιP» ll^ ι l ιl^ ll^ _|i __^ _f^ ι _l^ ιl^ - ιl^ - it~. ι|5. ιl-. ιt-. ιft. ιl-. o o VD o o p o tø co o\ ~i Mjι ω σι *> ϋι m σ\ uι _i ιt!. to t - p p p t to _o p p MΛi U -o p ι_D ∞ oo _π ω ιi^ Lπ Ln σι cn -~_ι ~ ~J ~j o oo Lθ Co ~~l cr_\ Lπ

Lπ Lπ i_3 so M Lπ Lπ Lπ Lπ ~J t>o _jι oo oo Ln Lπ co σι ιJ^ o sβ _.t--» o <£> μ^Λ Lo ω __ co σ_Λ w-. σ_\ tθ ω t\} n isJ Lπ ^Λ Ln ιi___. ιi--. SD t ι__. ω OT .f-.

>l^ ιl---. Lπ oo .l^ θ Ln o o sΩ cn t tθ Ln .ι~. cn ω ~ Lι to so μ^ so μ-> o ~j t s_o ω uι t_ι t_ι uι t_ι uι iJi w

ιi-> oo ιl~. ιl__. ιt~. ιI__> _fe ω ω co ~J to w

C0 Lw R cn ~ tsJ co o o o ω _ ιi___. μ^j w p pp p p pp p p μ p p p μ^Λ i-' μ-^> μ-^ι μ^j μ-^> μ-^ι μ-' H^ι μ-^ι μ-^ι μ^j μ-^ι μ-¹ μ-> μ-> μ-> μ-^ι μ-> μ-^ι μ-¹ μ-> μ-¹ μ-> μ-^, μ-^ι μ-^l μ-ⁱ μ μ p μ p μ μ μ p o o o o o o o o o o ooooooooooooooo oooooooooooo oooooooooooooooooooooo > O d < > O D c> o o o ooooooooooooooo ooooooσooooo ooooooooooooooσooooooo ι_n ui w w w uι υπ W ιi- ιh ι^ ω ω J ω ω ιii ^ ιii ^ ιi_ι ^ oi (Λ σι σι σι υi ui ιli ι^ ^ _i- ω ι^ ω ~J Lπ to o l-' M oo _ cn CD ~ so so ι_3 to Lπ ι_ι cn __n t ι)~. Lπ ~j ιt^ oo o -j L Lo to ∞

Lπ Lo ^ - (__j Lπ tsj ~j o co ιi_i ιi^ μ^j oo ιt-. t ~j Lπ co o-ι ιf-. - tj t cn ω ιl-. rø o w σι _ι^ co LιJ co Co Lπ o cn so cn so o o SD ~j oι ~θ Lw Lw so cx3 θ Lπ μ-> ιti o L_ Lπ _~ι t

ATOM 5907 O CYS D 123 60.,131 59.,513 45..676 1.00 58.47 8

ATOM 5908 CB CYS D 123 59. 784 61. 083 42. ,631 1. 00 54. 89 6

ATOM 5909 SG CYS D 123 58. 043 61. 147 43. 136 1. 00 52. 88 16

ATOM 5910 N ASP D 124 61. 104 61. 487 45. ,218 1. 00 58. 85 7

ATOM 5911 CA ASP D 124 61. 196 61. ,865 46. .619 1. 00 59. ,59 6

ATOM 5912 CB ASP D 124 62. ,205 62. ,994 46. ,816 1. ,00 60. .38 6

ATOM 5913 CG ASP D 124 62. 876 62. 937 48. ,182 1. ,00 61. ,57 6

ATOM 5914 ODl ASP D 124 62. 207 62. ,519 49, .151 1. ,00 60. ,87 8

ATOM 5915 OD2 ASP D 124 64. ,067 63. ,306 48, .289 1. ,00 61. .86 8

ATOM 5916 C ASP D 124 59. ,864 62. ,294 47. .198 1. ,00 59. ,72 6

ATOM 5917 O ASP D 124 59. ,310 63. .329 46, .822 1. ,00 59. .12 8

ATOM 5918 N VAL D 125 59. ,366 61. ,492 48. .131 1. ,00 60. .02 7

ATOM 5919 CA VAL D 125 58. .096 61, .758 48. ,795 1. ,00 61. .00 6

ATOM 5920 CB VAL D 125 57. .274 60, .469 48, .906 1. ,00 57, .98 6

ATOM 5921 CGI VAL D 125 56. .007 60, .721 49 .664 1, .00 56, .31 6

ATOM 5922 CG2 VAL D 125 56. ,973 59, ,946 47. ,526 1. ,00 58, .88 6

ATOM 5923 C VAL D 125 58. ,305 62. ,346 50, .199 1. .00 63. .48 6

ATOM 5924 O VAL D 125 57. ,391 62. ,956 50, .781 1. .00 64, .81 8

ATOM 5925 N SER D 126 59. ,511 62, ,177 50, .738 1. ,00 64, ,05 7

ATOM 5926 CA SER D 126 59. ,824 62. .684 52, .072 1. .00 64, .03 6

ATOM 5927 CB SER D 126 61, ,317 62, .517 52, .362 1, .00 63, .15 6

ATOM 5928 OG SER D 126 62, .088 63, .277 51 .455 1, .00 61, .24 8

ATOM 5929 C SER D 126 59. .426 64, .146 52, .233 1, .00 63, .55 6

ATOM 5930 O SER D 126 59. .745 64. .989 51, .396 1. ,00 62. .30 8

ATOM 5931 N GLY D 127 58. .716 64, .434 53 .315 1, .00 64 .29 7

ATOM 5932 CA GLY D 127 58. .285 65, .794 53 .564 1. .00 67 .20 6

ATOM 5933 C GLY D 127 56. .868 66, .085 53 .115 1, .00 68 .64 6

ATOM 5934 O GLY D 127 56. .368 67, .190 53, .321 1, .00 69, .55 8

ATOM 5935 N VAL D 128 56 .207 65 .103 52 .510 1, .00 70 .10 7

ATOM 5936 CA VAL D 128 54. .845 65, .323 52 .038 1. .00 71, .31 6

ATOM 5937 CB VAL D 128 54. .252 64. .077 51, .378 1. .00 69, .98 6

ATOM 5938 CGI VAL D 128 54. .873 63, .859 50 .035 1. .00 72, .53 6

ATOM 5939 CG2 VAL D 128 54, .476 62, .877 52 .271 1. .00 70, .16 6

ATOM 5940 C VAL D 128 53, .883 65 .707 53 .136 1. .00 71 .70 6

ATOM 5941 O VAL D 128 53, .089 66, .634 52 .978 1. ,00 69 .47 8

ATOM 5942 N ASP D 129 53 .960 64 .993 54 .251 1, .00 73 .53 7

ATOM 5943 CA ASP D 129 53 .022 65 .233 55 .320 1 .00 77 .21 6

ATOM 5944 CB ASP D 129 53, .171 64, .197 56 .428 1, ,00 78 .32 6

ATOM 5945 CG ASP D 129 51, .860 63 .985 57 .204 1, .00 80 .24 6

ATOM 5946 ODl ASP D 129 51, .521 62 .805 57 .509 1, . 00 81 .78 8

ATOM 5947 OD2 ASP D 129 51 .172 64 .996 57 .504 1 .00 78 .07 8

ATOM 5948 C ASP D 129 53 .027 66 .618 55 .915 1 .00 79 .33 6

ATOM 5949 O ASP D 129 52 .082 66 .963 56 .644 1 .00 80 .54 8

ATOM 5950 N THR D 130 54, .041 67, .433 55 .604 1, .00 80, .13 7

ATOM 5951 CA THR D 130 54, .048 68 .779 56 .171 1, .00 80 .39 6

ATOM 5952 CB THR D 130 5 .064 68 .702 57 .716 1 .00 83 .74 6

ATOM 5953 OG1 THR D 130 54 .418 67, .359 58 .114 1, .00 84 .65 8

ATOM 5954 CG2 THR D 130 52, .670 69 .136 58 .320 1 .00 81 .78 6

ATOM 5955 C THR D 130 55 .110 69 .794 55 .795 1 .00 78 .83 6

ATOM 5956 O THR D 130 56 .241 69 .440 55 .449 1 .00 77 .71 8

ATOM 5957 N GLU D 131 54 .701 71 .065 55 .921 1 .00 78 .93 7

ATOM 5958 CA GLU D 131 55 .520 72, .272 55 .705 1 .00 78 .30 6

ATOM 5959 CB GLU D 131 56 .825 72 .165 56 .518 1 .00 81 .28 6

ATOM 5960 CG GLU D 131 56 .641 72 .410 58 .024 1 .00 83 .84 6

ATOM 5961 CD GLU D 131 57 .696 71 .715 58 .856 1 .00 84 .29 6

ATOM 5962 OEl GLU D 131 58 .893 71 .821 58 .485 1 .00 85 .14 8

ATOM 5963 OE2 GLU D 131 57 .321 71 .068 59 .870 1 .00 82 .70 8

ATOM 5964 C GLU D 131 55 .869 72 .672 54 .295 1 .00 75 .98 6

ATOM 5965 O GLU D 131 55 .047 73 .205 53 .552 1 .00 74 .51 8

ATOM 5966 N SER D 132 57 .136 72 .452 53 .973 1 .00 75 .06 7

ATOM 5967 CA SER D 132 57 .689 72 .733 52 .665 1 .00 74 .59 6 -17υ

ATOM 5968 CB SER D 132 59.215 72. 882 52. 788 1. 00 75. 96 6

ATOM 5969 OG SER D 132 59. 812 71. ,733 53. ,401 1. 00 76. 36 8

ATOM 5970 C SER D 132 57. 316 71. 551 51. 753 1. 00 72. 89 6

ATOM 5971 O SER D 132 57. ,636 71. ,530 50. ,563 1. 00 73. ,06 8

ATOM 5972 N GLY D 133 56. 630 70. ,575 52. 337 1. 00 70. 56 7

ATOM 5973 CA GLY D 133 56. ,203 69. .406 51. ,599 1. 00 67. ,95 6

ATOM 5974 C GLY D 133 57. ,326 68. .647 50. .917 1. 00 66. ,74 6

ATOM 5975 0 GLY D 133 58. ,504 68. ,784 51. ,257 1. 00 65. .57 8

ATOM 5976 N ALA D 134 56. ,950 67, ,830 49. .942 1. 00 65, .62 7

ATOM 5977 CA ALA D 134 57. ,922 67. ,052 49. ,194 1. 00 63. 00 6

ATOM 5978 CB ALA D 134 57. ,506 65. .586 49. .145 1. ,00 62. .05 6

ATOM 5979 C ALA D 134 58. .060 67, ,597 47. .785 1. ,00 60. .69 6

ATOM 5980 0 ALA D 134 57. .215 68. .357 47, ,298 1. ,00 57. .71 8

ATOM 5981 N THR D 135 59. ,149 67, .206 47. ,139 1. .00 60. .08 7

ATOM 5982 CA THR D 135 59, .417 67, .619 45, .777 1, ,00 59, .14 6

ATOM 5983 CB THR D 135 60. .585 68, .590 45. .703 1, ,00 59. .67 6

ATOM 5984 OG1 THR D 135 60, .291 69. .735 46, ,516 1. 00 62. .19 8

ATOM 5985 CG2 THR D 135 60. .811 69. .031 44. ,263 1. 00 57. .77 6

ATOM 5986 C THR D 135 59. ,726 66. .387 44. .963 1. 00 57. ,95 6

ATOM 5987 0 THR D 135 60 . ,801 65, .804 45. .065 1. ,00 56. .51 8

ATOM 5988 N CYS D 136 58. .740 65, .995 44. .170 1. ,00 56, .67 7

ATOM 5989 CA CYS D 136 58. .825 64. ,836 43. ,314 1. ,00 55. .02 6

ATOM 5990 C CYS D 136 59, .172 65, .310 41, .906 1. ,00 55, ,53 6

ATOM 5991 O CYS D 136 58. .413 66. ,060 41, ,282 1. ,00 53. .64 8

ATOM 5992 CB CYS D 136 57, .475 64, .115 43, .347 1. .00 55, .35 6

ATOM 5993 SG CYS D 136 57, .280 62, .756 42. .175 1. .00 52, .04 16

ATOM 5994 N ARG D 137 60, ,331 64, .889 41. .414 1. ,00 55. .15 7

ATOM 5995 CA ARG D 137 60, ,752 65, .291 40, ,084 1. .00 56. .13 6

ATOM 5996 CB ARG D 137 62 .233 65, .664 40, .080 1. .00 59. .85 6

ATOM 5997 CG ARG D 137 62, .587 66, .818 40, .993 1. .00 64. .22 6

ATOM 5998 CD ARG D 137 64, .042 66, .718 41, .445 1. ,00 67. ,87 6

ATOM 5999 NE ARG D 137 64, .261 67, .425 42, .706 1. ,00 72. .81 7

ATOM 6000 CZ ARG D 137 64, .221 68 .753 42, .848 1. .00 76, .15 6

ATOM 6001 NHl ARG D 137 63 .975 69 .545 41, .798 1. .00 76, .59 7

ATOM 6002 NH2 ARG D 137 64 .408 69 .295 44 .051 1. .00 75 .96 7

ATOM 6003 C ARG D 137 60 .511 64 .156 39 .112 1. .00 54 .79 6

ATOM 6004 O ARG D 137 60 .844 63, .011 39, .394 1. ,00 55, .64 8

ATOM 6005 N ILE D 138 59 .935 64 .498 37, .966 1. .00 52 .46 7

ATOM 6006 CA ILE D 138 59 .618 63 .551 36 .923 1. .00 49 .86 6

ATOM 6007 CB ILE D 138 58 .092 63 .516 36 .686 1, .00 47 .60 6

ATOM 6008 CG2 ILE D 138 57 .769 62 .562 35 .565 1, .00 46 .55 6

ATOM 6009 CGI ILE D 138 57 .368 63 .120 37 .975 1, .00 44 .38 6

ATOM 6010 CDl ILE D 138 55 .873 63 .274 37 .903 1 .00 39 .29 6

ATOM 6011 C ILE D 138 60 .307 64 .004 35 .645 1 .00 50 .53 6

ATOM 6012 O ILE D 138 60 .056 65 .103 35 .163 1, .00 47 .86 8

ATOM 6013 N LYS D 139 61 .171 63 .158 35 .093 1, .00 52 .17 7

ATOM 6014 CA LYS D 139 61 .881 63 .497 33 .857 1, .00 53 .46 6

ATOM 6015 CB LYS D 139 63 .381 63 .195 33 .988 1, .00 54 .96 6

ATOM 6016 CG LYS D 139 64 .040 63 .838 35 .187 1 .00 59 .06 6

ATOM 6017 CD LYS D 139 65 .558 63 .761 35 .119 1 .00 60 .55 6

ATOM 6018 CE LYS D 139 66 .116 64 .685 34 .044 1 .00 62 .84 6

ATOM 6019 NZ LYS D 139 67 .604 64 .584 33 .930 1 .00 64 .96 7

ATOM 6020 C LYS D 139 61 .335 62 .715 32 .667 1 .00 52 .45 6

ATOM 6021 O LYS D 139 61 .269 61 .493 32 .708 1 .00 52 .48 8

ATOM 6022 N ILE D 140 60 .953 63 .411 31 .604 1 .00 51 .17 7

ATOM 6023 CA ILE D 140 60 .453 62 .723 30 .426 1 .00 51 .40 6

ATOM 6024 CB ILE D 140 58 .886 62 .781 30 .369 1 .00 52 .71 6

ATOM 6025 CG2 ILE D 140 58 .303 62 .478 31 .748 1 .00 53 .74 6

ATOM 6026 CGI ILE D 140 58 .387 64 .171 30 .003 1 .00 52 .18 6

ATOM 6027 CDl ILE D 140 56 .892 64 .354 30 .322 1 .00 51 .22 6

ATOM 6028 C ILE D 140 61 .078 63 .251 29 .123 1 .00 50 .75 6 ATOM 6029 O ILE D 140 61.189 64.451 28.918 1.00 50.51 8

ATOM 6030 N GLY D 141 61. 511 62. 340 28. 258 1. 00 48. 91 7

ATOM 6031 CA GLY D 141 62. 112 62. 735 26. 997 1. 00 48. 03 6

ATOM 6032 C GLY D 141 62. 036 61. ,611 25. 983 1. 00 47. 81 6

ATOM 6033 O GLY D 141 61. 636 60 . 511 26. 340 1. 00 50. 42 8

ATOM 6034 N SER D 142 62. 405 61. ,865 24. 729 1. 00 45. 08 7

ATOM 6035 CA SER D 142 62. 364 60. ,824 23. 713 1. 00 42. ,21 6

ATOM 6036 CB SER D 142 62. 872 61. ,334 22. 376 1. 00 43. ,40 6

ATOM 6037 OG SER D 142 63. 079 60. ,255 21. 482 1. 00 43. ,21 8

ATOM 6038 C SER D 142 63. 194 59. ,630 24. 126 1. 00 44. 37 6

ATOM 6039 O SER D 142 64. ,284 59. .758 24. 688 1. ,00 45. ,99 8

ATOM 6040 N TRP D 143 ^• 62. ,673 58. .452 23. ,825 1. ,00 46. ,12 7

ATOM 6041 CA TRP D 143 63. .338 57, .222 24. .196 1. .00 45. ,24 6

ATOM 6042 CB TRP D 143 62. ,300 56. .121 24. ,425 1. ,00 42, ,93 6

ATOM 6043 CG TRP D 143 62. .872 54. ,893 25. .051 1, .00 39, .90 6

ATOM 6044 CD2 TRP D 143 63. ,244 54. .737 26. .418 1. ,00 37, .42 6

ATOM 6045 CE2 TRP D 143 63. 740 53. ,425 26. 567 1. 00 37. ,64 6

ATOM 6046 CE3 TRP D 143 63. ,204 55. .581 27. .536 1. ,00 35. ,75 6

ATOM 6047 CDl TRP D 143 63. ,154 53. .702 24. .436 1. ,00 40. .17 6

ATOM 6048 NEl TRP D 143 63. .676 52, ,817 25. ,341 1. ,00 38. .55 7

ATOM 6049 CZ2 TRP D 143 64. ,187 52, .935 27. .788 1. ,00 38. .02 6

ATOM 6050 CZ3 TRP D 143 63, .647 55 .100 28, .741 1. .00 36 .62 6

ATOM 6051 CH2 TRP D 143 64. ,133 53, .784 28. .863 1. .00 39. .07 6

ATOM 6052 C TRP D 143 64. .348 56, .758 23. .170 1. .00 46, .24 6

ATOM 6053 O TRP D 143 65. .328 56, .109 23. .509 1. .00 48, .11 8

ATOM 6054 N THR D 144 64. .124 57, .080 21, .910 1, .00 45, .62 7

ATOM 6055 CA THR D 144 65 .047 56 .616 20 .894 1, .00 44 .68 6

ATOM 6056 CB THR D 144 64. .336 55 .633 19 .955 1 .00 44 .87 6

ATOM 6057 OG1 THR D 144 63 .155 56 .242 19 .421 1, .00 41 .93 8

ATOM 6058 CG2 THR D 144 63. .931 54, .394 20, .720 1, .00 44, .03 6

ATOM 6059 C THR D 144 65, .703 57 .710 20, .075 1, .00 46, .21 6

ATOM 6060 O THR D 144 66, .662 57, .452 19, .366 1, .00 47, .29 8

ATOM 6061 N HIS D 145 65. .198 58 .931 20, .173 1, .00 47, .13 7

ATOM 6062 CA HIS D 145 65, .772 60 .021 19, .403 1, .00 50, .18 6

ATOM 6063 CB HIS D 145 64, .672 60, .793 18. .679 1, .00 50, .55 6

ATOM 6064 CG HIS D 145 63 .961 59 .997 17 .630 1 .00 52 .45 6

ATOM 6065 CD2 HIS D 145 64 .369 59 .558 16 .416 1 .00 51 .92 6

ATOM 6066 NDl HIS D 145 62, .652 59 .589 17, .765 1, .00 50 .59 7

ATOM 6067 CEl HIS D 145 62 .282 58 .936 16 .679 1 .00 51 .27 6

ATOM 6068 NΞ2 HIS D 145 63, .305 58 .902 15, .844 1 .00 52 .81 7

ATOM 6069 C HIS D 145 66 .611 60 .990 20 .241 1 .00 52 .96 6

ATOM 6070 O HIS D 145 66 .147 61 .554 21 .236 1 .00 51 .74 8

ATOM 6071 N HIS D 146 67 .856 61 .179 19 .828 1 .00 53 .81 7

ATOM 6072 CA HIS D 146 68 .748 62 .081 20, .532 1 .00 55 .05 6

ATOM 6073 CB HIS D 146 70 .205 61 .691 20 ,267 1 .00 53 .71 6

ATOM 6074 CG HIS D 146 70 .555 61 .617 18 .816 1 .00 52 .77 6

ATOM 6075 CD2 HIS D 146 70 .425 62 .526 17 .821 1 .00 53 .89 6

ATOM 6076 NDl HIS D 146 71 .083 60 .487 18 .236 1 .00 49 .45 7

ATOM 6077 CEl HIS D 146 71 .261 60 .700 16 .945 1 .00 49 .76 6

ATOM 6078 NE2 HIS D 146 70 .869 61 .929 16 .667 1 .00 51 .93 7

ATOM 6079 C HIS D 146 68 .489 63 .521 20 .094 1 .00 56 .51 6

ATOM 6080 O HIS D 146 67 .682 63 .770 19 .185 1 .00 58 .53 8

ATOM 6081 N SER D 147 69 .190 64 .455 20 .738 1 .00 57 .97 7

ATOM 6082 CA SER D 147 69 .054 65 .902 20 .497 1 .00 58 .69 6

ATOM 6083 CB SER D 147 70 .097 66 .646 21 .332 1 . 00 58 .36 6

ATOM 6084 OG SER D 147 71 .365 66 .032 21 .179 1 .00 58 .90 8

ATOM 6085 C SER D 147 69 .114 66 .404 19 .049 1 .00 57 .67 6

ATOM 6086 O SER D 147 68 .570 67 .470 18 .727 1 .00 55 .79 8

ATOM 6087 N ARG D 148 69 .768 65 .647 18 .180 1 .00 57 .54 7

ATOM 6088 CA ARG D 148 69 .878 66 .061 16 .790 1 .00 59 .37 6

ATOM 6089 CB ARG D 148 71 .054 65 .340 16 .126 1 .00 64 .67 6 r~- so so r- so ι ι so co t-- so so vo so co co so α_> c^ so so so so so so co ι so so co so co [ so so so so

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P P P P P P P P P P R P P P P P P P O P P P R P P R P P P P P P P R R R P P P P R R Q P P P P P P P P P P P P R P P P P P

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LO LO O LO O LO O LO o LO CM CM CO CO "fr "fr LO LO o CD

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ATOM 6212 CA TYR D 164 43.,236 72.,353 36.,946 1.00 61..14 6

ATOM 6213 CB TYR D 164 43. .901 71. ,828 35. ,675 1. 00 62. .34 6

ATOM 6214 CG TYR D 164 43. ,794 72. ,756 34. ,501 1. ,00 62. ,07 6

ATOM 6215 CDl TYR D 164 44. ,937 73. ,264 33. ,887 1. ,00 62. ,29 6

ATOM 6216 CEl TYR D 164 44. ,846 74. ,152 32. .813 1. 00 64. .14 6

ATOM 6217 CD2 TYR D 164 42. .547 73, .151 34. .016 1. ,00 ^•63, .36 6

ATOM 6218 CΞ2 TYR D 164 42. .438 74, .038 32. .940 1. ,00 65. .18 6

ATOM 6219 CZ TYR D 164 43. ,594 74, .536 32. .337 1. ,00 65, .18 6

ATOM 6220 OH TYR D 164 43. .495 75, .380 31. ,240 1. ,00 65, .32 8

ATOM 6221 C TYR D 164 43. .257 71, .263 38. ,000 1. .00 59, .77 6

ATOM 6222 0 TYR D 164 42. ,602 70, .231 37. ,853 1. ,00 59, .16 8

ATOM 6223 N PHE D 165 44. .008 71. .497 39. .068 1. ,00 57, .70 7

ATOM 6224 CA PHE D 165 44. .113 70, ,518 40, .143 1. ,00 56, .00 6

ATOM 6225 CB PHE D 165 45, .105 70, .988 41, ,202 1, ,00 53, .27 6

ATOM 6226 CG PHE D 165 45. 635 69. .885 42. ,053 1. 00 51. .93 6

ATOM 6227 CDl PHE D 165 46, .436 68 .891 41, .502 1, ,00 50 .62 6

ATOM 6228 CD2 PHE D 165 45. .326 69, ,820 43. .398 1. ,00 52, .41 6

ATOM 6229 CEl PHE D 165 46, ,922 67 .845 42, .283 1. .00 49 .13 6

ATOM 6230 CE2 PHE D 165 45. .807 68. .777 44, .188 1, ,00 52, ,20 6

ATOM 6231 CZ PHE D 165 46. .608 67 .788 43, .624 1. ,00 51 .98 6

ATOM 6232 C PHE D 165 42. .773 70, .241 40. .801 1, ,00 55, .90 6

ATOM 6233 O PHE D 165 41. ,970 71. .149 41. .005 1, ,00 56, ,82 8

ATOM 6234 N SER D 166 42. .524 68, .980 41. .126 1. ,00 55, .56 7

ATOM 6235 CA SER D 166 41. .273 68 .627 41, .771 1. .00 55 .90 6

ATOM 6236 CB SER D 166 41 .115 67 .117 41 .887 1, .00 55 .69 6

ATOM 6237 OG SER D 166 39. ,855 66, .799 42, .457 1. .00 55, .69 8

ATOM 6238 C SER D 166 41 .280 69 .229 43, .158 1, .00 56 .73 6

ATOM 6239 O SER D 166 42, .315 69 , .229 43. .839 1. .00 56, .74 8

ATOM 6240 N GLN D 167 40, ,121 69. .729 43. .578 1. ,00 57, .58 7

ATOM 6241 CA GLN D 167 39, .999 70, .353 44. .892 1. .00 57, .81 6

ATOM 6242 CB GLN D 167 38, .867 71, .383 44. .885 1. .00 59, .24 6

ATOM 6243 CG GLN D 167 37. ,541 70, .794 44. .439 1. .00 63, .59 6

ATOM 6244 CD GLN D 167 36 .485 71 .854 44, .107 1. .00 65 .57 6

ATOM 6245 OEl GLN D 167 36 .054 72 .607 44, .979 1, .00 65 .98 8

ATOM 6246 NE2 GLN D 167 36. .067 71 .909 42, .831 1. ,00 65 .54 7

ATOM 6247 C GLN D 167 39. ,752 69, .328 45. .977 1. ,00 56, .65 6

ATOM 6248 O GLN D 167 39 .990 69 .598 47, .151 1, ,00 56 .95 8

ATOM 6249 N TYR D 168 39. .293 68, .145 45, .586 1. ,00 56, .16 7

ATOM 6250 CA TYR D 168 39. .014 67 .091 46, .556 1, .00 53 .65 6

ATOM 6251 CB TYR D 168 37, .798 66, .297 46. .096 1, ,00 54, .14 6

ATOM 6252 CG TYR D 168 36 .675 67 .217 45, .707 1, .00 53 .82 6

ATOM 6253 CDl TYR D 168 36, .446 67, .545 44, .371 1, .00 53 .19 6

ATOM 6254 CEl TYR D 168 35, .445 68, .454 44, .020 1. .00 54 .20 6

ATOM 6255 CD2 TYR D 168 35 .880 67 .816 46, .681 1, .00 52 .39 6

ATOM 6256 CE2 TYR D 168 34, .881 68, .722 46. .342 1. .00 52, .03 6

ATOM 6257 CZ TYR D 168 34 .670 69 .035 45, .016 1, .00 53 .04 6

ATOM 6258 OH TYR D 168 33, .683 69, .917 44. .689 1. .00 53 .97 8

ATOM 6259 C TYR D 168 40 .181 66 .162 46. .851 1, .00 52 .39 6

ATOM 6260 0 TYR D 168 40, .025 65, .185 47. .575 1. .00 53 .02 8

ATOM 6261 N SER D 169 41 .347 66 .479 46, .299 1, .00 51 .48 7

ATOM 6262 CA SER D 169 42 .543 65 .686 46, .513 1, .00 51 .84 6

ATOM 6263 CB SER D 169 43 .664 66, .151 45, .584 1, .00 52 .14 6

ATOM 6264 OG SER D 169 44 .878 65 .483 45, .881 1, .00 50 .95 8

ATOM 6265 C SER D 169 43 .001 65 .828 47. .953 1, .00 53 .72 6

ATOM 6266 O SER D 169 42 .832 66 .880 48. .570 1, .00 51 .67 8

ATOM 6267 N ARG D 170 43, .583 64 .761 48. .487 1, .00 54 .84 7

ATOM 6268 CA ARG D 170 44, .079 64, .778 49. ,850 1. ,00 54, .97 6

ATOM 6269 CB ARG D 170 44 .460 63 .366 50 .297 1 .00 54 .29 6

ATOM 6270 CG ARG D 170 43 .369 62 .647 51. .081 1, .00 57 .60 6

ATOM 6271 CD ARG D 170 43 .436 61 .124 50 .955 1 .00 58 .91 6

ATOM 6272 NE ARG D 170 4 .726 60, .543 51. .323 1, .00 61 .45 7 CD en en o oo IV⁾ IV⁾ O en o en 4^ o o en o en o en en to to to to to to to to ;___ι ;> ;y to to ;_y to ;μ to ! to to to β β 3 >- β 3 ^ β t-3 β !-3 β ι-3 ι-3 3 B β β β ι-3 ι-3 μ3 β β β β ι-3 3 3 ι- 3 β ι-3 β μ3 β ι-3 ^ β β β β β

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K K ffi ffi ffi ^ i> ' ^ | ^l p w ω tn ω (n w w !n H B H B B B B lιl t^, t^l t t tr^l _r^, lr' _r^l t^H _^H _^H _^H _^H t^H _^H _^H t^H ffi ffi ffi K IS ffi ffi ffi K K K pα pd pd pd p3 ^ ^ ?3 ^ p p t^H _^H [^H fl y fl ^ 'ti 't « ^ d c! α d α d α i _. __ H H t. d ts ci α i i α c! K H t_ l_- H t_ W t_ H M t- ( n -__ Q α α α o α oα αα αααα αααα αα α α α αα αα α αo ppμμμμ p p p pp μ ppp p μ p p p p μ-^l ι-^> ι-^ι μ^j μ^A μ-^ι μ^j μ-^ι μ^j μ^j _l__ _|__ ₍_- _l_ι pΛ _|-__ι ₍__. _|-_-i μ__. _|_-. pι |__ |__ p_ pι

~j ~j ~j ~ ~j ~j - ~^j -o -J - -o ~-~ -o -j ~ -J -o -~J ~ ~j ~j ~j ~J ~ -~α ~j -J ~ ~ - - ~ -j ~j ~j ~^ --JJ --~_I -J ~J ~J ~J ~J ~J ~J ~J ~J ~J ~J ~J ~J ~j ~ -~j -j - cn OT -n σ~ c^ c. _^ _n Lπ Lπ Lπ Ln -π ui Lπ ι)-* ιi_. ι^ ιl-» .ι~_^ O O O O

Uι σι W ϋi ϋπ ui uι ϋi ui ljι tΛ iΛ tΛ Ui iΛ i_ι uι uι uι w ui (_n uι U ui -i uι iJi trι uι t> f. uι σι uι Cπ ι(^ ι^ ι!-. |f~ ιt^ __^ ι^ lfe _l^ tf^ _l^ __i |l^ _P> l^ ιl^ (_^ _^ _l^ -l^ ιl-> _^ lP» l _ 0 _ ⁽J⁾ ~l <_\ ⁽_l ^l |l_. i Ul Ul Ul tIl J Ul Ol Ul ^ i|i |O l _ ^ l U tO t O O l0 10 P O O o so cx> -J ~J t» -o ~J ~j Lπ _ Co so ~J to ~J co oo ~J Lπ Lrι υι cn Lπ t ω ~j σ-ι μ-» ιt-. ω co ω Lπ (-¹ L o c c θJ ~j σ^ o iΛ Lϋ ~j Lπ o ~o -^ι μ-ι oo ω Lπ _t)-> σι s ^j ~ ~ ∞ μ-^» ω ω μ-> ∞ c» ω ω ιo oo W c _ -j o so co ^j M ∞ .ι^ ω ι^

CO l_3 LO CO il-> 00 ~J tO CO O _ri CO O Ln Ln __n O O -J O U_⁾ tv3 Ln CO M SO i^ O IO OO h-¹ L tO tO OT ~J --3 ~J ~J ~J ~J -~J ~J ~J ~J ~J -J ~J ~J -J -J ~J ~J --J ~J ~J ~J ~J ~0 ~J -O ~J ~J ~J ~J ~J -J ~0 -J ~^ m ω i^ ii- ω w ii- t t -o ω ^ to u m ^ m ui ui fc n ui ω t ω it- iii W iii ω o o to t p μ o o t ω u o ra α) P Ui iΛ^j μ p o tD ^ ω ιa ιo m ^ ~ι ω o ιii ω p ra (» p p ι^ ω - _ i σι iι o ι_) ui p oi ι^ m σι m _i ω o ι^ P θ ι^ ω .ι^ ∞ ~j -^ι so __^ c_o .!-» ω ιi~. .i-» co oo μ-^ι __^ o c- ~j Lπ ω tNj ∞ s ω ω ω so ιi-. σ- ιl^ θ Lπ Lπ Lπ σ^ t _n ι_-. Lπ ω oo - -j o ~j L μ^j σ^ σ-ι i -' o o o Lπ π ω

W L _l^ ~ o^ Lπ u_ι oo » D θo ∞ _π H^> -θ Lrι __ ⁽ ι μ^j ω α5 i o ^ ⁽_θ L o ~J OT o ~ o o o μ-> -¹ _ μ-^ι so -o co _rι σι μ^j c) Lπ L ιi-. ιt-. ι_j π c» υ c _l^ o __^ _π Ln to oo c^ v 1 0 C^ CO I_ l_O ^ _n i-» _ H> I-' t-» iI-. ||^ i^ iP~ CX> Ln l_D VO ll^ O _0 0 |^ lO _^ t-> μ-¹ i-¹ ^ i-¹ s-¹ μ-> ι-» μ-¹ \- μ> μ-> ι-> μ^j μ-' H μ-s μ^ H ^j μ^j μ^j -' μ^j μ^Λ i-' _-^ι μⁱ μ^j μ-' μ-^ι μ-^l t-^l Pⁱ μ-> -> μ-> μ-' μ-' μ-^ι μ-> μ-> μ-> μ-¹ μ-¹ P P P o o o o o o o o o o o o o o o ooooooooooooooooooooooooooooooooooooooooo o o CD C CD O O O O C CD O CD Cl O oooooo noσ DOooooocDooooooo ooooooo oooooooo oo cn w"i c c_ -n cn c c cn α-ι θ _ σι _ c _ m cn . o^ c c Lπ c^ _^ Lo -j ω ι_a n c_ Lπ ι(_. ι)~. Ln Lπ w σ- so so D ~j Lπ ιi^ (_o ω u_ι to ^ μ-> co ^ ιf^ c^ o θ - L so cn c» -θ Ln L t n ιl^ wj s Ln σι l--' ω o ιi-» o oo t o tsJ Lπ ω W !θ Lπ .l^ t σι Lπ ~j so SD _π co oo ∞ c_o L_i ι!-> -J co co -J -J _. σ~ t α_ι tO _ o u_> .^ c_n co crι σ^ -o cxι σι cΛ -_n cJi cn -J cxι cn oo α3 c_n cn w ~J co o c_n σι o^

ATOM 6334 C THR D 177 59..165 73,.144 36,.739 1..00 71..66 6

ATOM 6335 O THR D 177 59, ,373 71 .973 37 .111 1. .00 73, ,56 8

ATOM 6336 N GLN D 178 59. .417 73, .568 35, .501 1. .00 71. .95 7

ATOM 6337 CA GLN D 178 59, ,941 72, .667 34 .488 1, .00 72. .06 6

ATOM 6338 CB GLN D 178 58, ,932 72, .511 33, .347 1. .00 74, .14 6

ATOM 6339 CG GLN D 178 57, .466 72 .700 33 .754 1. .00 76. ,97 6

ATOM 6340 CD GLN D 178 56, .497 72, .041 32 .772 1, .00 78. ,22 6

ATOM 6341 OEl GLN D 178 56 .603 72 .230 31 .551 1 .00 79 .44 8

ATOM 6342 NE2 GLN D 178 55. .544 71, .266 33 .302 1. .00 76. .76 7

ATOM 6343 C GLN D 178 61. .219 73, .240 33 .936 1. .00 71. .25 6

ATOM 6344 O GLN D 178 61, .226 74 .368 33 .462 1. .00 71. .24 8

ATOM 6345 N LYS D 179 62, .291 72, .461 33, .979 1. .00 71. ,70 7

ATOM 6346 CA LYS D 179 63, .593 72 .904 33 .474 1. .00 71. .59 6

ATOM 6347 CB LYS D 179 64. ,553 73, .170 34, .642 1. ,00 73, .63 6

ATOM 6348 CG LYS D 179 63 .906 73 .953 35 .800 1, .00 77, .80 6

ATOM 6349 CD LYS D 179 64, .795 74 .018 37 .040 1. ,00 78, .53 6

ATOM 6350 CE LYS D 179 64, .016 74 .470 38 .273 1. .00 79, .16 6

ATOM 6351 NZ LYS D 179 62, .899 73, .537 38, .610 1. .00 77, .90 7

ATOM 6352 C LYS D 179 64. .173 71, .807 32, .601 1. ,00 70, .50 6

ATOM 6353 O LYS D 179 64, .549 70 .754 33 .112 1, .00 69, .32 8

ATOM 6354 N LYS D 180 64, .252 72, .044 31 .294 1. .00 69, .56 7

ATOM 6355 CA LYS D 180 64, .803 71 .039 30 .382 1, .00 69, .55 6

ATOM 6356 CB LYS D 180 64, .581 71 .464 28 .924 1, .00 69, .05 6

ATOM 6357 CG LYS D 180 65, .462 72, .584 28, .419 1, .00 68. .35 6

ATOM 6358 CD LYS D 180 66, .773 72 .041 27 .860 1, ,00 66, .86 6

ATOM 6359 CE LYS D 180 66. .550 71, .200 26 .619 1. .00 63. .97 6

ATOM 6360 NZ LYS D 180 66. .096 72, .020 25, .476 1. .00 64. .54 7

ATOM 6361 C LYS D 180 66, .293 70 .795 30 .642 1. .00 68. .87 6

ATOM 6362 O LYS D 180 66, .869 71 .406 31 .536 1, .00 69, .83 8

ATOM 6363 N ASN D 181 66. .905 69, .879 29. .897 1. .00 68. .37 7

ATOM 6364 CA ASN D 181 68 . .326 69. .615 30. .060 1. . 00 70. .05 6

ATOM 6365 CB ASN D 181 68. .711 69. .461 31. .540 1. .00 70. .86 6

ATOM 6366 CG ASN D 181 67. .808 68, .533 32, .291 1. .00 71. .68 6

ATOM 6367 ODl ASN D 181 67, .498 67, ,446 31. .823 1. .00 74. .38 8

ATOM 6368 ND2 ASN D 181 67. .395 68, .945 33, .487 1. .00 72. ,61 7

ATOM 6369 C ASN D 181 68, .905 68, .449 29. .281 1. ,00 70. .12 6

ATOM 6370 O ASN D 181 68. .535 67 .303 29 .491 1. .00 68. .91 8

ATOM 6371 N SER D 182 69, .844 68 .760 .28 .385 1. .00 71, .81 7

ATOM 6372 CA SER D 182 70, .519 67, .744 ^'27, .577 1, ,00 71, ,83 6

ATOM 6373 CB SER D 182 71. .361 68, .418 26, .495 1, ,00 70. .60 6

ATOM 6374 OG SER D 182 71 .817 67 .463 25 .557 1, .00 71, .86 8

ATOM 6375 C SER D 182 71. .405 66 .866 28 .482 1. .00 71, ,03 6

ATOM 6376 O SER D 182 71, .794 67 .281 29 .572 1, ,00 72, .13 8

ATOM 6377 N VAL D 183 71. .715 65 .653 28, .037 1. .00 70. .45 7

ATOM 6378 CA VAL D 183 72. .528 64, .736 28, .842 1. ,00 69. ,61 6

ATOM 6379 CB VAL D 183 71, .728 64 .221 30 .066 1, .00 69. .93 6

ATOM 6380 CGI VAL D 183 70, ,268 63, ,988 29. .671 1, ,00 71. ,71 6

ATOM 6381 CG2 VAL D 183 72, .331 62 .909 30 .584 1, ,00 68, .31 6

ATOM 6382 C VAL D 183 73, .046 63 .521 28 .069 1, .00 69 , .82 6

ATOM 6383 O VAL D 183 72 .317 62 .887 27 .305 1, .00 69 .28 8

ATOM 6384 N THR D 184 74, .314 63, .194 28, .272 1. .00 71. .03 7

ATOM 6385 CA THR D 184 74. .898 62, ,041 27, .596 1, , 00 72. .40 6

ATOM 6386 CB THR D 184 76, .314 62 .360 27 .027 1, ,00 71. .67 6

ATOM 6387 OG1 THR D 184 76, .207 63 .364 26 .010 1, .00 69, .65 8

ATOM 6388 CG2 THR D 184 76 .944 61 .110 26 .404^' 1, .00 71, .24 6

ATOM 6389 C THR D 184 74, .997 60 .901 28 .602 1, .00 73, .76 6

ATOM 6390 O THR D 184 75, .273 61 .132 29 .786 1, .00 74, .26 8

ATOM 6391 N TYR D 185 74, .749 59 .679 28 .139 1. .00 74, .82 7

ATOM 6392 CA TYR D 185 74, .818 58 .515 29 .024 1, .00 76, .20 6

ATOM 6393 CB TYR D 185 73, .477 57, .755 29, .046 1. .00 77. .17 6

ATOM 6394 CG TYR D 185 72, .286 58, .637 29 .324 1, .00 77, .03 6 ATOM 6395 CDl TYR D 185 71.,822 59.,527 28..362 1.00 77.16 6

ATOM 6396 CEl TYR D 185 70. 781 60. 416 28. ,640 1. 00 78. ,65 6

ATOM 6397 CD2 TYR D 185 71. 676 58. 643 30. ,578 1. 00 78. ,44 6

ATOM 6398 CE2 TYR D 185 70. .629 59. ,532 30, .873 1. ,00 78, .76 6

ATOM 6399 CZ TYR D 185 70. ,190 60. ,417 29, .897 1. ,00 78. .44 6

ATOM 6400 OH TYR D 185 69. ,173 61. ,311 30. .160 1. ,00 78. .64 8

ATOM 6401 C TYR D 185 75. ,909 57. 595 28. .525 1. 00 76. ,37 6

ATOM 6402 O TYR D 185 76. .062 57. .403 27 .320 1. .00 75, .86 8

ATOM 6403 N SER D 186 76. ,669 57. ,031 29, .454 1. ,00 78. ,41 7

ATOM 6404 CA SER D 186 77. 762 56. .127 29. .097 1. 00 80. ,47 6

ATOM 6405 CB SER D 186 78. .353 55. .494 30, .361 1. .00 80, .37 6

ATOM 6406 OG SER D 186 77. ,324 55. ,000 31. .202 1. 00 80. .82 8

ATOM 6407 C SER D 186 77, .259 55. .042 28, .139 1. ,00 81. .49 6

ATOM 6408 O SER D 186 77. .977 54. .637 27 .205 1. .00 80, .86 8

ATOM 6409 N CYS D 187 76. .018 54. .601 28, .370 1. ,00 82. ,03 7

ATOM 6410 CA CYS D 187 75. .366 53. ,573 27. .553 1. ,00 82. .11 6

ATOM 6411 C CYS D 187 75, ,259 54. ,005 26. .123 1. 00 82. .74 6

ATOM 6412 O CYS D 187 75, .445 53. .226 25 .179 1, .00 81, .67 8

ATOM 6413 CB CYS D 187 73. .908 53. ,360 27. .980 1. ,00 82. .28 6

ATOM 6414 SG CYS D 187 72, .725 54. .778 27 .707 1. ,00 81 .64 16

ATOM 6415 N CYS D 188 74, .954 55, .287 25 .990 1. ,00 83, .43 7

ATOM 6416 CA CYS D 188 74, .614 55, ,827 24, .701 1. ,00 83, .03 6

ATOM 6417 C CYS D 188 75. ,379 57. ,070 24, .204 1. ,00 81, ,94 6

ATOM 6418 O CYS D 188 75. .401 58. .127 24 .860 1. ,00 81, .77 8

ATOM 6419 CB CYS D 188 73. .091 56. .059 24, .777 1. ,00 83. .56 6

ATOM 6420 SG CYS D 188 72. .115 54. ,783 25, .740 1. ,00 85. .15 16

ATOM 6421 N PRO D 189 76. ,000 56, .945 23 .013 1. .00 80 .60 7

ATOM 6422 CD PRO D 189 75, ,862 55, .676 22 .263 1. ,00 80, .05 6

ATOM 6423 CA PRO D 189 76 .809 57, .921 22 .254 1. .00 78 .99 6

ATOM 6424 CB PRO D 189 76, .804 57, .341 20 .836 1, .00 79 .15 6

ATOM 6425 CG PRO D 189 76, .835 55. .852 21 .097 1. .00 80, .06 6

ATOM 6426 C PRO D 189 76. .386 59. .408 22, .258 1. . 00 76, .71 6

ATOM 6427 O PRO D 189 77. .106 60. .265 22, .777 1. ,00 76. .06 8

ATOM 6428 N GLU D 190 75. .237 59. .713 21 .663 1, .00 73 .54 7

ATOM 6429 CA GLU D 190 74. .762 61, .101 21, .583 1. ,00 70, ,67 6

ATOM 6430 CB GLU D 190 73 .735 61, .233 20 .462 1, ,00 72 .95 6

ATOM 6431 CG GLU D 190 73 .941 60, .272 19 .292 1, .00 76 .22 6

ATOM 6432 CD GLU D 190 74, .959 60, .778 18, .284 1, ,00 77, .17 6

ATOM 6433 OEl GLU D 190 74 .920 61 .987 17 .949 1, .00 75 .78 8

ATOM 6434 OE2 GLU D 190 75 .786 59, ,961 17 .819 1, .00 78 .06 8

ATOM 6435 C GLU D 190 74, .113 61, .576 22 .874 1. ,00 67 .13 6

ATOM 6436 ^• O GLU D 190 74, .060 60, .842 23, .861 1. ,00 66, .77 8

ATOM 6437 N ALA D 191 73 .595 62 .797 22 .852 1 .00 63 .73 7

ATOM 6438 CA ALA D 191 72 .924 63 .362 24 .027 1 .00 63 .96 6

ATOM 6439 CB ALA D 191 73 .293 64 .833 24 .188 1, .00 60 .91 6

ATOM 6440 C ALA D 191 71 .398 63 .226 23 .935 1 .00 63 .09 6

ATOM 6441 O ALA D 191 70 .824 63 .324 22 .848 1. .00 63 .27 8

ATOM 6442 N TYR D 192 70 .737 63 .015 25 .073 1, .00 61 .86 7

ATOM 6443 CA TYR D 192 69 .284 62 .883 25 .077 1 .00 60 .02 6

ATOM 6444 CB TYR D 192 68 .874 61 .483 25 .544 1 .00 58 .87 6

ATOM 6445 CG TYR D 192 69 .185 60 .408 24 .531 1, .00 59 .77 6

ATOM 6446 CDl TYR D 192 70 .447 59 .804 24 .491 1 .00 59 .82 6

ATOM 6447 CEl TYR D 192 ■70 .762 58 .849 23 .514 1 .00 59 .91 6

ATOM 6448 CD2 TYR D 192 68 .234 60 .030 23 .568 1 .00 59 .23 6

ATOM 6449 CE2 TYR D 192 68 .534 59 .084 22 .592 1 .00 60 .37 6

ATOM 6450 CZ TYR D 192 69 .803 58 .496 22 .566 1 .00 61 . 99 6

ATOM 6451 OH TYR D 192 70 .120 57 .582 21 .581 1 .00 61 .54 8

ATOM 6452 C TYR D 192 68 .590 63 .938 25 .922 1 .00 59 .37 6

ATOM 6453 O TYR D 192 68 .594 63 .874 27 .150 1. .00 61 .63 8

ATOM 6454 N GLU D 193 67 .986 64 .909 25 .248 1 .00 59 .03 7

ATOM 6455 CA GLU D 193 67 .280 65 .992 25 .915 1 .00 60 .46 6 ATOM 6456 CB GLU D 193 66.832 67.,054 24.898 1.00 61.02 6

ATOM 6457 CG GLU D 193 67. 985 67. ,781 24. 196 1. 00 65. 53 6

ATOM 6458 CD GLU D 193 67. 522 68. ,937 23. .292 1. 00 66 . 58 6

ATOM 6459 OEl GLU D 193 66 . 678 69 . ,760 23. 739 1. 00 66. 15 8

ATOM 6460 OE2 GLU D 193 68. 017 69. ,023 22. 138 1. 00 66. 88 8

ATOM 6461 C GLU D 193 66. 066 65. ,455 26. ,658 1. 00 61. 32 6

ATOM 6462 O GLU D 193 65. .498 64. .428 26. ,278 1. ,00 61. ,10 8

ATOM 6463 N ASP D 194 65. .6-82 66. .157 27. ,724 1. 00 62. 11 7

ATOM 6464 CA ASP D 194 64. ,533 65, .788 28. .537 1. ,00 60. ,32 6

ATOM 6465 CB ASP D 194 64. .855 64, .571 29, .416 1. ,00 60. ,68 6

ATOM 6466 CG ASP D 194 65. .759 64, .907 30. .589 1. ,00 61. ,25 6

ATOM 6467 ODl ASP D 194 66. ,929 64. ,453 30. ,591 1. ,00 62. ,58 8

ATOM 6468 OD2 ASP D 194 65. ,297 65, .619 31, .509 1. .00 61. .10 8

ATOM 6469 C ASP D 194 64. ,086 66. ,951 29, ,417 1. ,00 59. ,85 6

ATOM 6470 O ASP D 194 64. .890 67 .793 29, .816 1. .00 60. ,03 8

ATOM 6471 N VAL D 195 62. .792 66, .993 29. ,704 1. .00 57. .38 7

ATOM 6472 CA VAL D 195 62. .225 68 .024 30. .538 1. ,00 55. ,36 6

ATOM 6473 CB VAL D 195 60. .864 68, .480 30, .001 1. ,00 52. .24 6

ATOM 6474 CGI VAL D 195 60. .179 69, .394 31, .001 1. ,00 51. ,69 6

ATOM 6475 CG2 VAL D 195 61. .058 69, .189 28. .693 1. .00 52. .14 6

ATOM 6476 C VAL D 195 62. .044 67, .460 31. ,935 1. ,00 56. .36 6

ATOM 6477 O VAL D 195 61. ,452 66 .412 32 .114 1, .00 57. .76 8

ATOM 6478 N GLU D 196 62, .571 68, .151 32. .930 1. ,00 58, .67 7

ATOM 6479 CA GLU D 196 62, .425 67, .712 34, .303 1. .00 58. .26 6

ATOM 6480 CB GLU D 196 63, ,754 67, .833 35, .035 1, .00 ^'58, .61 6

ATOM 6481 CG GLU D 196 63. .725 67, .326 36, .460 1, ,00 61. .95 6

ATOM 6482 CD GLU D 196 65, .062 67 .533 37, .172 1, ,00 63, ,50 6

ATOM 6483 OEl GLU D 196 66 .083 67 .014 36, .679 1, .00 62, .21 8

ATOM 6484 OE2 GLU D 196 65, .099 68 .218 38, .222 1. .00 65, .74 8

ATOM 6485 C GLU D 196 61 .370 68 .598 34, .959 1. .00 58, .08 6

ATOM 6486 O GLU D 196 61 .500 69 .822 34 .997 1, .00 59, .87 8

ATOM 6487 N VAL D 197 60. ,305 67, .979 35. .452 1, .00 57, .22 7

ATOM 6488 CA VAL D 197 59, .242 68 .721 36, .104 1, .00 54, .36 6

ATOM 6489 CB VAL D 197 57, .863 68 .304 35, .567 1 .00 52 .68 6

ATOM 6490 CGI VAL D 197 56, .772 69 .095 36, .255 1, .00 49, .60 6

ATOM 6491 CG2 VAL D 197 57 .809 68 .517 34 .068 1 .00 50 .84 6

ATOM 6492 C VAL D 197 5 .317 68 .420 37 .587 1 .00 55 .10 6

ATOM 6493 O VAL D 197 59 .367 67 .264 37, .995 1 .00 55, .27 8

ATOM 6494 N SER D 198 59, .351 69 .467 38, .399 1, .00 56, .68 7

ATOM 6495 CA SER D 198 59 .413 69 .284 39, .839 1 .00 56 .39 6

ATOM 6496 CB SER D 198 60, .487 70 .188 40, .448 1, .00 55, .89 6

ATOM 6497 OG SER D 198 61 .789 69 .767 40, .066 1 .00 57 .83 8

ATOM 6498 C SER D 198 58 .058 69 .593 40 .448 1 .00 56 .61 6

ATOM 6499 O SER D 198 57 .536 70 .698 40, .317 1 .00 56 .25 8

ATOM 6500 N LEU D 199 57 .481 68 .597 41 .101 1 .00 56 .92 7

ATOM 6501 CA LEU D 199 56 .189 68 .770 41 .728 1 .00 56 .84 6

ATOM 6502 CB LEU D 199 55, .303 67 .561 41, .468 1, .00 57, .08 6

ATOM 6503 CG LEU D 199 53 .981 67 .553 42 .243 1 .00 57 .99 6

ATOM 6504 CDl LEU D 199 53 .094 68 .726 41 .834 1 .00 57 .12 6

ATOM 6505 CD2 LEU D 199 53 .272 66 .246 41 .971 1 .00 58 .22 6

ATOM 6506 C LEU D 199 56 .354 68 .953 43 .220 1 . 00 57 .85 6

ATOM 6507 0 LEU D 199 56 .625 67 .998 43 .950 1 .00 58 .46 8

ATOM 6508 N ASN D 200 56 .207 70 .192 43 .671 1 .00 58 .52 7

ATOM 6509 CA ASN D 200 56 .315 70 .486 45, .084 1 . 00 57, .07 6

ATOM 6510 CB ASN D 200 57 .017 71 .827 45 .311 1 .00 59 .47 6

ATOM 6511 CG ASN D 200 57 .126 72 .184 46. .781 1 .00 61. .26 6

ATOM 6512 ODl ASN D 200 57 .508 71 .359 47 .613 1 .00 60 .78 8

ATOM 6513 ND2 ASN D 200 56 .792 73 .423 47 .108 1 .00 63 .13 7

ATOM 6514 C ASN D 200 54 .886 70 .533 45 .593 1 .00 55 .28 6

ATOM 6515 O ASN D 200 54 .108 71 .422 45 .242 1 .00 53 .93 8

ATOM 6516 N PHE D 201 54 .549 69 .554 46 .419 1 .00 53 .26 7 ATOM 6517 CA PHE D 201 53.,218 69..444 46..973 1.,00 51.,91 6

ATOM 6518 CB PHE D 201 52. ,408 68. ,434 46. .168 1. 00 49. ,89 6

ATOM 6519 CG PHE D 201 52. 870 67. ,013 46. ,348 1. 00 46. ,59 6

ATOM 6520 CDl PHE D 201 52. .068 66, ,086 47, .003 1. .00 45. .61 6

ATOM 6521 CD2 PHE D 201 54. ,133 66, .613 45. .903 1. ,00 46. .86 6

ATOM 6522 CEl PHE D 201 52. .519 64, .779 47, .218 1. .00 45, ,68 6

ATOM 6523 CE2 PHE D 201 54. .597 65, .312 46, .112 1. ,00 44. .48 6

ATOM 6524 CZ PHE D 201 53. .788 64, .394 46. ,772 1. .00 44. .43 6

ATOM 6525 C PHE D 201 53. .360 68, .940 48 .386 1, .00 53, .35 6

ATOM 6526 O PHE D 201 54. .456 68, .570 48, .818 1. .00 52. .18 8

ATOM 6527 N ARG D 202 52. ,238 68, .902 49. .093 1. .00 55. .22 7

ATOM 6528 CA ARG D 202 52. .211 68. .426 50. .470 1. .00 57. .74 6

ATOM 6529 CB ARG D 202 52. .632 69 .546 51 .412 1. .00 58, .53 6

ATOM 6530 CG ARG D 202 51. .564 70, .612 51, .484 1. .00 62. .76 6

ATOM 6531 CD ARG D 202 51. .956 71, .797 52, .313 1. .00 64, .76 6

ATOM 6532 NE ARG D 202 50. .901 72, .806 52, .296 1. .00 64. .52 7

ATOM 6533 CZ ARG D 202 51. ,046 74. ,035 52. .779 1. ,00 65. .00 6

ATOM 6534 NHl ARG D 202 52. .206 74, ,409 53, ,323 1. .00 65. .86 7

ATOM 6535 NH2 ARG D 202 50, .045 74, .896 52, .708 1. .00 62. .46 7

ATOM 6536 C ARG D 202 50, .788 67, .997 50, .835 1. .00 57, .64 6

ATOM 6537 O ARG D 202 49, .822 68, .392 50, .186 1. .00 55, .63 8

ATOM 6538 N LYS D 203 50, .668 67 .189 51 .878 1. .00 58, .55 7

ATOM 6539 CA LYS D 203 49. .359 66, .759 52, .332 1. .00 59, .55 6

ATOM 6540 CB LYS D 203 49. :505 65, .708 53, .428 1, ,00 60, .97 6

ATOM 6541 CG LYS D 203 48. .195 65 .258 54 .031 1. .00 62, .61 6

ATOM 6542 CD LYS D 203 48. .445 64, .319 55, .194 1. .00 66, .11 6

ATOM 6543 CE LYS D 203 47. .142 63, .813 55 .784 1, .00 68, .33 6

ATOM 6544 NZ LYS D 203 46, .380 62, .985 54, .804 1. .00 69, .98 7

ATOM 6545 C LYS D 203 48, .702 68, .008 52, .914 1, .00 60, .27 6

ATOM 6546 O LYS D 203 49. .402 68, .886 53, .428 1, .00 60, .55 8

ATOM 6547 N LYS D 204 47. .374 68, .105 52, .832 1. ,00 59, .32 7

ATOM 6548 CA LYS D 204 46. .680 69 .260 53 .395 1, .00 60 .40 6

ATOM 6549 CB LYS D 204 45, .221 69, .284 52 .947 1. .00 59. .66 6

ATOM 6550 CG LYS D 204 45. .054 69, .738 51 .495 1, .00 56 .15 6

ATOM 6551 CD LYS D 204 43, .652 69, .489 50, .974 1. .00 52, .10 6

ATOM 6552 CE LYS D 204 43, .593 69 .775 49 .488 1. ,00 52 .88 6

ATOM 6553 NZ LYS D 204 42. .334 69, .320 48, .856 1, .00 54, .65 7

ATOM 6554 C LYS D 204 46. .776 69 .201 54 .919 1. ,00 62, .27 6

ATOM 6555 O LYS D 204 47, .031 68 .129 55 .479 1, .00 63 .85 8

ATOM 6556 N GLY D 205 46, .590 70, .344 55 .587 1, .00 61 .70 7

ATOM 6557 CA GLY D 205 46, .701 70 .390 57 .043 1, .00 61 .46 6

ATOM 6558 C GLY D 205 45, .432 70, .704 57 .821 1. .00 60, . 96 6

ATOM 6559 OT1 GLY D 205 44 .364 70 .809 57 .191 1 .00 61 .45 8

ATOM 6560 OT2 GLY D 205 45 .495 70 ,835 59 .067 1 .00 60 .53 8

ATOM 6561 CB PHE E 1 68, .481 57 .493 1 .362 1, .00 63 .85 6

ATOM 6562 CG PHE Ξ 1 68 .496 56 .384 0 .357 1, .00 65 .93 6

ATOM 6563 CDl PHE E 1 67, .431 56, .207 -0 .526 1, .00 67 .13 6

ATOM 6564 CD2 PHE E 1 69 .549 55 .462 0 .345 1, .00 67 .48 6

ATOM 6565 CEl PHE E 1 67, .410 55, .116 -1 .409 1, .00 68 .65 6

ATOM 6566 CE2 PHE E 1 69 .548 54 .364 -0 .528 1 .00 67 .48 6

ATOM 6567 CZ PHE Ξ 1 68 .481 54 .185 -1 .406 1 .00 69 .10 6

ATOM 6568 C PHE E 1 67 .191 59, .419 2 .218 1, .00 61 .93 6

ATOM 6569 0 PHE Ξ 1 ^•67, .898 59, .384 3 .225 1, .00 62 .32 8

ATOM 6570 N PHE E 1 68, .457 59, .591 0 .037 1 .00 62 .93 7

ATOM 6571 CA PHE E 1 67 .655 58 .712 0 .943 1 .00 62 .89 6

ATOM 6572 N ASP E 2 66 .011 60 .038 2 .205 1 .00 61 .01 7

ATOM 6573 CA ASP E 2 65 .524 60 .730 3 .406 1 .00 60 .82 6

ATOM 6574 CB ASP E 2 64, .448 61 .754 3 .027 1, .00 59 .66 6

ATOM 6575 CG ASP E 2 63 .263 61 .126 2 .346 1 .00 61 .52 6

ATOM 6576 ODl ASP E 2 62 .587 60 .347 3 .035 1 .00 62 .72 8

ATOM 6577 OD2 ASP E 2 63 .006 61 .396 1 .142 1 .00 60 . 96 8 ATOM 6578 C ASP E 2 65..012 59,,731 4..459 1.,00 60.,89 6

ATOM 6579 O ASP E 2 64. ,990 58. .525 4. ,216 1. ,00 62. .95 8

ATOM 6580 N ARG E 3 64. ,624 60. .214 5. 635 1. ,00 60. ,20 7

ATOM 6581 CA ARG E 3 64. .161 59, ,321 6. ,697 1. .00 57, .08 6

ATOM 6582 CB ARG E 3 63. .746 60. .128 7. ,933 1. ,00 56, .21 6

ATOM 6583 CG ARG E 3 64. .906. 60. .475 8. ,878 1. ,00 56. ,67 ^' 6

ATOM 6584 CD ARG E 3 65. .314 59. .266 9. ,702 1. ,00 57. ,53 6

ATOM 6585 NE ARG E 3 66. .519 59, .426 10. ,524 1. .00 58. .61 7

ATOM 6586 CZ ARG E 3 66. .825 60, .497 11. ,258 1. ,00 60. ,79 6

ATOM 6587 NHl ARG E 3 66. .024 61. .559 11. .294 1. .00 61. ,35 7

ATOM 6588 NH2 ARG E 3 67. ,943 60. .499 11, ,975 1. ,00 58. ,97 7

ATOM 6589 C ARG E 3 63. .008 58, .447 6. .244 1. .00 56, .93 6

ATOM 6590 O ARG E 3 62, .949 57 .256 6. .567 1. .00 58, .08 8

ATOM 6591 N ALA E 4 62. .102 59. .033 5. ,473 1. ,00 54, ,21 7

ATOM 6592 CA ALA E 4 60. .937 58, .311 4. ,993 1. ,00 52. .85 6

ATOM 6593 CB ALA E 4 60. .002 59, .262 4. .270 1. .00 50, .53 6

ATOM 6594 C ALA E 4 61. ,342 57. .168 4. ,075 1. ,00 53. ,00 6

ATOM 6595 O ALA E 4 60. ,858 56. .056 4. ,225 1. ,00 53. ,30 8

ATOM 6596 N ASP E 5 62. .235 57. .443 3. .132 1. ,00 54, ,00 7

ATOM 6597 CA ASP Ξ 5 62. .692 56 .433 2. .190 1. ,00 54. .02 6

ATOM 6598 CB ASP E 5 63. .702 57. .021 1. ,197 1. .00 56, .37 6

ATOM 6599 CG ASP E 5 63. .153 58. .223 0, .435 1. .00 60 .25 6

ATOM 6600 ODl ASP E 5 62. .018 58, .154 -0. .072 1. .00 61, .70 8

ATOM 6601 OD2 ASP E 5 63. .864 59, .247 0. ,327 1, ,00 64, .63 8

ATOM 6602 C ASP E 5 63. .341 55 .278 2. .924 1. ,00 54, .45 6

ATOM 6603 O ASP E 5 63. .192 54, .127 2. .532 1. ,00 54, .26 8

ATOM 6604 N ILE E 6 64. .060 55 .582 3, .997 1, .00 54 .54 7

ATOM 6605 CA ILE E 6 64. .734 54 .535 4, .755 1, .00 55, .28 6

ATOM 6606 CB ILE E 6 65, .727 55 .121 5. .781 1. .00 56, .90 6

ATOM 6607 CG2 ILE E 6 66, .476 53 .991 6, .489 1, .00 56 .40 6

ATOM 6608 CGI ILE E 6 66, .728 56, .031 5. .068 1, .00 58, .74 6

ATOM 6609 CDl ILE E 6 67. .833 56, .589 5. ,976 1. .00 60. .73 6

ATOM 6610 C ILE E 6 63, .765 53, .617 5. .482 1. .00 53, .47 6

ATOM 6611 O ILE E 6 63 .830 52 .401 5, .322 1, .00 53 .23 8

ATOM 6612 N LEU E 7 62, .883 54, .199 6. .290 1, .00 53. .23 7

ATOM 6613 CA LEU E 7 61, .897 53 .423 7, .033 1, .00 52, .57 6

ATOM 6614 CB LEU E 7 61. .060 54 .354 7 .899 1, .00 52 .03 6

ATOM 6615 CG LEU E 7 61. .862 55 .020 9, .017 1. .00 52, .39 6

ATOM 6616 CDl LEU E 7 61, .074 56 .183 9, .607 1, .00 53, .72 6

ATOM 6617 CD2 LEU E 7 62 .185 53 .989 10 .070 1 .00 47 .50 6

ATOM 6618 C LEU E 7 61, .003 52 .660 6, .065 1, .00 52 .40 6

ATOM 6619 O LEU E 7 60, .665 51 .503 6, .302 1, .00 53, .43 8

ATOM 6620 N TYR E 8 60 .644 53 .311 .967 1. .00 51 .20 7

ATOM 6621 CA TYR E 8 59 .810 52 .707 3. .951 1 .00 52 .74 6

ATOM 6622 CB TYR E 8 59. .622 53 .686 2, .804 1 .00 54 .75 6

ATOM 6623 CG TYR E 8 58 .825 53 .102 1 .660 1 .00 60 .00 6

ATOM 6624 CDl TYR E 8 • 57 .448 52 .902 1 .773 1 .00 59 .81 6

ATOM 6625 CEl TYR E 8 56 .723 52 .341 0. .734 1 .00 59 .72 6

ATOM 6626 CD2 TYR E 8 5 .453 52 .717 0. .465 1 .00 61 .59 6

ATOM 6627 CE2 TYR E 8 58 .727 52 .148 -0 .580 1 .00 59 .67 6

ATOM 6628 CZ TYR E 8 57 .367 51 .967 -0 .433 1 .00 59 .94 6

ATOM 6629 OH TYR E 8 56 .646 51 .411 -1 .457 1 .00 63 .44 8

ATOM 6630 C TYR E 8 •60 .399 51 .405 3 .404 1 .00 54 .02 6

ATOM 6631 O TYR Ξ 8 59 .692 50 .414 3, .259 1 .00 54 .84 8

ATOM 6632 N ASN E 9 61 .688 51 .411 3 .082 1 .00 53 .58 7

ATOM 6633 CA ASN E 9 62 .338 50 .224 2, .559 1 .00 52 .96 6

ATOM 6634 CB ASN E 9 63 .790 50 .524 2 .182 1 .00 58 .69 6

ATOM 6635 CG ASN E 9 63 .907 51 .445 0 .966 1 .00 62 .10 6

ATOM 6636 ODl ASN E 9 62 .908 51 .771 0, .321 1 .00 64 .59 8

ATOM 6637 ND2 ASN Ξ 9 65 .137 51 .861 0 .645 1 .00 63 .43 7

ATOM 6638 C ASN E 9 62 .297 49 .112 3 .584 1 .00 52 .17 6 CD en en 4 00 oo ιv> ro O en σ en o en o en o en o en toto to tototototo toto tototototo totototototo

_ . „ e . . - _ . - - . B e ^ . ^ e ^ β _ . _ - _ _ . . _ - . . ι _ _ . _ _ _ _ _ - _ _ _ _ . . _ _ ri _ _ _ _ _ _ . _

Ω O O O O O O O O O O O O O O O O O O Ω O O O O O O O O O O O O O O O O O O Q O O O O O O O O O O O O O O O O O O O Q O g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g c^ σ_Λ σι n crι σι _»> cr_\ _^ __n σ- c_n cn _w-ι o~, cn c σι σϊ σ cn -_^ σι o^ o. o-ι θ θ^ w^ σι n - σι _. σ c cn _ -ή cn _^ cn σΛ cn c n cn w-ι w^ o o so so so so so so so so co co cx) oo cxι c_o ∞ cα co co -~j ~j -o ~j ~j ~j -j ~ ~J ~J cn cn c^ > co ~J c_ Cn ι^ LιJ to μ-> o tø σ3 --α __n Lπ ιl-» »J t -^l o o o ~j o-ι Lπ ιi^ ω c H θ ^ a o Ω Ω a o a a a Ω Ω a O Ω O Ω Ω O Ω O Ω O Ω O Ω Ω Ω a O Ω Ω ω > Ω Ω ω ^ M H ϋ ω ; K S N a t_ α Ώ ωΩ ; OΩΩ θ ΩΩΩ ω to μ-> t p to p t P P p to j it) ^ ^ ^ fl fl fl < ^ ω θ) m i_ ω O i3 β ι3 β ι3 ι3 ι n Q 00 Q Q _I. l> ^ H H H H H H H H

W ^ ^ ^ W 3 ^ ^ ^ ^ ^ ^ » ^ ^ 3 ^ p ^ H M t. t- t. t- !ι; ffi K ffi K W K t^, t t t^H t^H t^H t^H t^H t^H p pd f jd ?d ?d d L . I .Λ j , j _rl t_n p_ t_l t_^H. t_→ t_^H t_^ _ ^fO O O O O O O O Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω pd pd pd jd pd ^ pd pd ^ pd ^ tri fd a a a a a Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω H M M D- t- M B

M M M W M W M H M M M M P M H M J ta tS M μ-> μ μ-->> μ H^j> H μ^j i--' -' μ^j -ⁱ _^ μ^j μ^ μ-^ι μ-⁴ i-^{ι Λ Λ} P^Λ v-' μ^j i--^ι μ-^s μ-' μ-^> μ-> μ-^> μ-^ι μ-» μ-^ι μ^j μ-' μ-> m m cfi -Λ σi σi σi w iΛ W U i αi w ui tΛ αi oi ^ i^ i^ ^ ili i^ w ω ω ω oJ W ω to to to M

Lπ σi π Lπ Lπ Lπ Lπ Lπ ^ c π o^ π Lπ cn σi cn c c^ cπ cn αΛ - - n σi c o^ σi so o so oo oo so oo so μⁱ M o so so o o o o μ-> so o to μ-> μ-> μ^j tθ M to ω to .-> o ∞ ~θ Lπ cn _^ -J ∞ ∞ ∞

Lπ ιP~ θ ιP~ ~j u_ι σ_Λ θ3 ~ -o ~ _n ~o ~ -o _n so __^ co Lπ ~j is3 __n -n ιt^ o cn Lπ ω p p m m ω oι co m o ι^ _i - μ ι_n ιti co to c ω o tθ ι^ _o co μ ιo t_π to (a p m ω to p ω p ffl ^ ra p m m uι m o t <_o rι L μ^j to o Lπ (θ n w ιt^ Lπ c^ σι C ~j ω so ~ - s ι-' ι)^ cj c^

C_J OJ ) _fe _.l-. _0 ||-_» i|_-- U) W _O

~j oo rø μ-^l o o o o o3 so ι(-» w ω n ιl^ cn cn ~o ι_-) μ-' so σι ~j o π oo ~J o -j o μ-^> μ-^ι μ^j cn tso _ o _o ιi ii^

~j ~j -o co Lπ -> L t_o tNj tθ Ln ∞ μ-> -> σι ___π so ιl^ Lπ Lπ Ln Lπ c^ ρ^l ι_^ . o σι uJ o ~o t H' oo μ-' -χj w cn co ^j _» N_) o σι Lo cx) Lπ -J t^ (j σ^ o t _n ι^j

M μ-> f-> ι-> h¹ μ ω μ o t-^y o iB io uι ω _- uι _i Uι θι ~ι ~] m <Λ ∞ ~] oι ι ω _- o ω w to w p ω ρ ρ o P io u t)i ι_ι co m ~i (_i M oι oι oi (]i m oι (xι j ffl o o o so o Lπ ~j θ Lπ ι-' C so ~J θ Lπ L _o ~ Lι_⁾ -' σ' ~J ι)^ co o CD o μ-' - so cxi ιi^ Lπ t> __n so j-. ιl^ so (_j o co Lπ μ^j -j ∞ n -o c ι^ ^ o o σι co ι_-» κJ so o CD S o ιo s cx3 -j so ω ui oi -jι ~] p ω ~] ~ι u o -j ^ t o ~ι uι ι_ι ω ιo _i ^ u u) ∞ w ι ui t o μ p uι σi ιi- θ3 ui iι) ω L o uι m ~] - u μ p p p μ μ^j _-> H t-^ι μ^{i j j} μ^j μ^Λ μⁱ i-ⁱ μⁱ P-^ι ι-' i-> ι-' μ-' i-^> ι~^ι μ^j μ-^ι -' H μ-^, μ-^l μ-' μ-' t-' μ-' _-^j μ-> μ-> μ-^ι μ-> μ-^l ι-' i-^ι μ-^> μpp p μ p μ p p p oooooooooo ooo ooooooooooooooo ooooo oo ooooo oooooooooo oooooooooo ooo o ooo oo ooo ooooooooooooooooooo oooooooooooooooooooooooooo oo uι ^ l_ι uι w w ι_η iΛ Uι σι _n oι oι m oι Ui -i w ijι u oι m oι m m i)i t)i __ι lΛ l_ι l_ι ι_ι uι uι u σι l_ι ω o Lo o H o μ^j o _j^ π _π ~j ιP> θΛ σ" L_ι so ~J o ∞ s o cn tsj -' o c» cπ Ln Lπ Lπ Lπ ιt-» M

~ μ-> tsj i ) (Xi so so o ~j ~J Lo ~J ~ c_o ~J so Lo o -o sD Lo μ^j cn μ^Δ ιf^ c_o to L to so so μ-' cn σι ∞ co so M ._o vθ ι!-- -o so o Lπ σ_^ so so μ^j -o ω .[~. μ^j o _.l^ cn c_o so ~J o Lπ _I^ L_ so Lυ cn c^ cn cn cn -o cχ> cn ~j -- _> ~j _rι _fι -n _n ~J -o _rt co σ> cr> ~o co σ- cn cx. cn

toto to to to toto to to to to to to to to to to toto to to to 3 β β 3 3 θ >-3 B ι-3 ι-_ '-3 >- H ^ β β i-3 >- H H β >-3 <- !-3 !- t-3 ι-3 ι-3 >-3 β ι^ β 3 ι-3 >-3 β β

O O O O O O O O O O O O O O O O O O O O O O O O O O O O Q O O O O O O O O O O O O O O O Q O O O O Q O Q Q O O Q O O O O ggggggggggggg ggggggg ggg gggggggggggggggggggggggggggggg gg g gggg σ^*ι c c c^ c n _rι c c c c c w-ι cΛ cn cy! n σ c cn σ"ι c c w-\ σ- cn o^

~J ~J ~J ~J ~J -J -J -J ~J ~J -O ~J ~J ~0 -J ~J ~J -J ~J ~J ~0 ~J -J .~_] ~J ~J ~J -J -J -O ~J .~J ~J -O .~- -J ~^ -J ~J ~J ~J ~J ~J — 1 ~~) ~ c Lπ Lπ π Lπ Lπ Lπ _π Lπ Lπ Lπ ι^ ιi~. ιf_. ιi^ ι~ ι ιt_ ιj__. ιl-. ||-. L LJ Lo _ o _ o _ o __ o __ o __ o _ o _ o o ul ^_J to P o w (!O J m w ^ u ) P o ιo ra ^■o _n ι_l ^ w to p o u) ∞ M t!l Ul _i u ^) P o _ tD M Cft W ll- l_ _ p

Ω Ω Ω O Ω a Ω Ω Ω Ω Ω O Ω S O Ω Ω Ω Ω a O Ω Ω O Ω Ω a Ω Ω Ω Ω Ω a O Ω Ω Ω Ω O Ω O Ω Ω Ω Ω Ω a O Ω O Ω Ω Ω

O Ω td > a N Pd t_ Ω t Pd Pd O Ω td i Ώ Ω ω > Ω td > ϋ O Ω Ω ω Ω Ω td O O Ω ID t to _-» t v-» P P M to μ-> to

^ ^ ^ ^ ^ ^ to ^ ^ ^ ^ ^ ^ Da ^ ^ Ω Ω Ω Ω Ω Ω Ω Ω Ω 3 β >-3 ι-3 ι-3 β β . __ .. . _ . . m . p H H H H <J <! <; ; : ' !» ;_t< ; ;P' ' ;_ pd pd pd pd pd pd pd pd pd pd t^H tH |rⁱ -^H i< C> tA ffi a a a a w d d pd p ja jd d tr¹ f _^H F t¹ ^fti πj iu j ^fu Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω a a a a a ϊd pd pd pd pd ?d pα o θ Ω O O O O H H H H W H H H £ Λ O CO CO CO y ifl ⁱt) O

H H a H H B M M t. H H H a H H _. H t. l_. a H _. t- _. H I_. W W H H

_ to _0 _O t tO IO _O K) _O K⁾ t t t M M » _0 _0 -O t M t _O l t U t M _ M t t tO M - t t _ ~ H ■— P i— P <— P i— i- P r P i— P ι~ Pι— -> μ^j p μ-^Λ P ι->

^ ιfι (- (i (!, u ω u ^{) )} u u u u u ω to t ι - to _o ι t M p μ μ μ p μ o o o o o o o O uSO) iSDD iSDO iLDO iS_O) iSO- iS_O) iSoO ιOiO) CO CO CO OO OO ~J ~J -J ~J ~

~J

Ln co σι p ω c cn -j co Lπ 3 P ~j ω ~j to _ ~j o o σι π _. ω _o M .^ s ω ~j ^

Lπ ~ o o ιt-. ~J so o so co ιi^ (χι M cn Lo ~J co co oo __^ p so o -J oa Lπ c_n o __-. ~J θ o o Lπ Lπ ιi-. ~j so ∞ c p _ ιi^ oo ω o ιJ^ w w o oo ιt^ ~ Lπ n ι o ~ θ Lπ M Lυ ιo tNθ θ -l^ o _t^ θJ -o co - p

W J W tO IO tO J L LO J cn cn ro oo o ι_o J θ M π OT o ω -J θ ∞ Lo ~ _π -o l~¹ ~J ω Lπ Ln oo ιF~ ~o u. ω Lπ Lπ t μ^j P o P cn ω cΛ θ ∞ co p Ln σ^ ιt~. t ω LιJ so o -J so co αi -θ oo cD Lϋ oo o __^ o o θ -θ o t ~j ~j o w co u. ~j o _n w to ~j co tsj co so σι Lπ ω ω ~j ~j so o M o o o ~J o co ~o so to cxι cn M ~J θ oo co o ιl^ o ~J ιl^ ω ιt-.

P P M P M P M M t-> ^' ι-^» μ

~J Cϋ L0 S0 -0 C0 C0 C0 _0 ω ιI-. Lπ 0l σι ~J ~J 00 C0 C» O l_> 00 C0 -J LD ~J 00 S O O O O O O O t M P ift. - C C C P O O ~J OO O O O μ-> o No O μ

(Λ (!H!> - vl sl - 0 I M O (. lJl _ O O lD O ϋi ω μ t μ i!) 0 ~l (D Ul sl U p μ „ -_, „ ___ ___ . v O O lO CO O U) O t>) Ul (Il (D O U1 0 it, t O O J l_l (_) i ιo . ω . co o _ P . ιt> u - ι .i.- p . C .D . t .o σ _ι_ u_ι ijJ θ - u_ι .tθ. -.θ. P. u. ω o __M. o_ ~i - u.. p. _i o _ uι t _n . o _ p . _. c. ι_-. o Ln ∞ n ∞ π _o -J .!^ _!^ ~J ∞ -j v^ ω o ω cn t .£. ω- ω- L-u . LO i c _o mm oui_ ss!! θm3 ~ji j~i χxii ω- ~ιι μμ _to (cioι μμ μμ oo ιιt_)) UU oo wm μμ __-^ -- μμ Hμ mm oo __oj μμ ^_- mm siι oι o t. ~ι ii) Ui o ~ι ω j o o o ~i -i iι) ι t_ι ~ι ιo i- μ to lo P to ω to μ-> t-> μ-> μ-> P^ P P P p p M P p μ-' μ-' p p -' H p p μ-' μ-' p M H P P P P P P

OO O OO OOO O O O O O O O OOO OO O O O OO O OO O O OO O O O O O OOOO O O OO OO O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O so ι_3 so co oo cn c_o so so so so so co oo oo oo c^ ι_ι ω o (iι uι ijι uι i_ w u t o ^ fc fc ^ P M o ω o _ ~i -i ui - -) t M ω μ o o t ^ u μ u ω

H ~ ιl_i Lo ι_3 Lπ LιJ ~j w c ~J ι(i Co co o o w so ~ Lπ ~J ui Lπ t co ι> ∞ _!-» ω o i>o t_o _l|~>

∞ cn cn cn ~J co cn -~J ~J _rι -o σ^ c_n cn c_n ~J ∞ c_n -j α-> σ. σ. cn _n -~- ∞

CD en en 4> ω oo IV) ιv> O cn σ en o cn o en o on en

c_n σ. cn _ _n _ c^ _^ c -n σ> _r> Λ σ\ c c - σ n cn cn c. σι _ _^ _^

CO CO C» CO CO CO CO CX) 0000 CX3 0O CXI CX- CO CX) CX> CX1 0O 00 00 CX3 ~J -O ~J ~J ~0 ~J ~J ~J -~J tO t p P P P P P P P P P O O O O O O O O O O O SD sO O O sO O SO O θ α_> C)O CO CO CO CX> Cθ α_> C-0 00 ~J ~J ~_ -J ~J -J -J -J -J ~J C^ p^j < o-ι s_oo m oo ~j _ π >^ ω .o p i-- -o -θ n υι .l-. NJ o sD _o ~j σ. Lπ .l-» ω

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H M H H H H H H H H H H H H M M M H H H M H H H H H H H H H H H H H H H H H H H H H H H H H M H H H H H H H H H H H M H t cr_ σι _n crι cn cn cn cn w cΛ c_n cn σ. σ. cn cπ cn Ln Lπ Lπ L_n Lπ Lπ cn cπ Ln Ln Ln Lπ L^

P P P P P P P O O O O O O O O SO SO SO SO SO So CO C» C_O CX> CO CX_' ∞ CO CO C-0 ∞ C_O C_0 00 ~J ~J .-J -J ~J ~J -^

~ ~j -o ~j ~j ~j ~j ~ ~J cn σ. OT _ ~ ~ ~J -o ~J -o ~J ~J -J ~J C^ cn _n cn cn cn cn cn cn ~J ~J -~^

CX) ~J Cn i!-. L O P O P -J OO OO O O P tO tN3 lti |I^ CO tO t tsO C31 ~J Cn OO O CO -J CO SO P t P tO ϋi ιl- o ω (_n ιi_ θ3 Ui o o m -J P σι ^ o o -j (i io ι ω ιi- ^ ^ tΛ -θ ιi_ i3i co θD iD M u ιo ι^ p o ~] o ~) p ιo u m m θ M t_^ Lπ rø to so U3 _l^ <-n to p .l^ p cn co so ~ co oJ _o p cπ ιJ^ cn so to oo Lπ o ω o p o o σι p ω

_π p to ~J o ∞ cn so P θ Ln .Iι» .l^ OT P Co co ~ oJ θo --j isJ o ~J t>J c_o so Ln oJ o >)^ p ~J to σ. w

P P P M t0 tO tO ιl_- IO P P P C C IO O P L0 C0 CO tsJ ιI_- t0 0J L0 L0 p ρ to tO !O P P lNJ L0 J L0 0π cn Lπ ι(-» L0 0^ co co cn θJ p s co p ι_. _jι ~j oo Lπ t -n σ. c_o Lo ₁^ Lπ o o c» ι_^ t-w o so .F~ cn .^ _θ Ln p to cϋ ^ o (_n ~J θ Lπ oo Lπ o -, cπ o ~J o o co .J^ -J _n ~J -J o ~j ~j Ln co ~j _o σ_\ tθ Ln M io oo -o ω tø -j on so co oπ so p cn on _ p p lsJ cn Ln o oo co -J p ι__ι so to p t>J t co oo to oo oπ o on M ~j ι(__^

P P P P P P P P P P P P P P P P P P P P P P P P P tO P P _O I -O J ^ M J > 3 _O t C tO tO _O O tO W C t_ CO ts_l C c. -j cn ~J cn ~^j ∞ Lσ so o ra o P o P Cθ ->J tθ Lo ω Lπ cn cn c_o so ~J Ln _n ∞ cn - cn -J ~^ Ln _o ~J _π ι_. Lπ ~J to Lπ ω oo o o -J to cn cn ω L ~j o cn o oo Lo o ιi-> cn o c^ cn Lo .(^ ι^

So tO t>O O O O D O -J ω o CO t)^ C tO ~J ω oo OJ ~0 ~-) Cn ι^ 0 .t_» ~J _ ι!^ ∞ P O Cn ιC^ c» Lo M cn co p p oo oo ιF~ Lπ cn ~J θo Lo p L Ln ι>o oo cn -l^ o -J P L -j t_o co so ~J ~J Lθ _o to cn c» ∞ P P P P P P P P P P P PPPPPPPP P P P P P P P PPPPPPPPPP P P P P P P P PPPPPPPPPP ooooooooooooo oo ooooo ooo oo ooo ooooo ooooooooooooooo ooooooo ooo oo oooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo

∞∞∞~J~J c c.ncΛw cnc LπLπU.LnLn _n _nLn.^.^ι!_.ι!->ι5__ι^ ∞_.o__->oσΛωo -θ_o ι_?θ3Lπo_oι_oLnt ι_5cnσ- __ Lπtoω o tsoω^ppιj~. L^ t P Ln P t P ~J P O CO Ln CO _O So J CO O CO P CO OO SO SO P 00 so to ~j o o co ~ Lθ ιi__. cn p p Ln - oo cn Lθ ιii. Ln oo o so Ln ιi~. p o Lθ o oo so ~θ Ln o Lo cn u ιoro o3 θ oo u ω ι to p w o co to _o co w m σι «) so to p 00 00 o ~j co cn Ln Ln t Lθ ι|__=. σ. o ιl^ Lo co oo oo w cn P θo so ~j -j cn c_n Lo to o so Lπ Lπ co p oo o

CD en cn IV) O en o en 4^ oo oo IV) o en o on o en en to to to to to to to to to ;)__^ to to to to to to to to to to to to *. ^ !»' ^l ' Sa ^l ^' |w | 3 B ^ ι-3 ι^ ι-3 β β β ι-3 β ^ ι- β ι^ β ι-3 β β μ3 β β B v β β β β ι-3 ι^ ι^ ι-a ι-3 ι-3 ι^ ι-3 β β β ι- ⁽-3 β '^ β ι-3 ι^ O O O O Ω O O O O O Ω O Ω Ω O O O Ω O O O O O O Ω O O O O O O O O O O O O O Ω O Q O Q O O Q O O Q O O O Q O O O Q O Q Q g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g g

~J -J ~J ~J ~J ~J ~J ~J ~J -J ~J ~J ~J -J -J ~J ~J ~J ~J -J -J -~J -_ -~3 ~J -J ~J ~J - ~J ~J ~J ~J ~J ~J -J -J ~J ~J ~J ~J ~J -J ~J ~J ~J -J ~J ~J p Pp Pμ^j Pp Pp Pp Pp Pp Pp Pp PpPpPPPPPPPpPPPPPpPP Pp Pp PP PP p P P oO oO oO oO oO oO oO oO oO oO oO O O O O O O .-. C-D-- O--. O--. O.-. O--. O--. O--. O--- C-D-. O.-- C--. C-Z-3- — O _ _■ C0 W tJ _O .NJ CO _O P P P P P P P P P P O O O O O O O O O O lO <-3 0 β L0 α l___ S0 ~0 l0 C0 C0 _0 CD C0 C0 C0 CX> m uι ^ ω ι μ o - θ3 J m _i ω w p o _ cθ 'J o\ tjι ^ U -- P θ ifl ffl ~i (jι ui ιli ω t p o u) tD tn uι ^ tι) to p o ι_) Co ^ cn oπ ιf_- θo co p o ~o co ~

Ω Ω g O Ω O Ω Ω a O Ω O Ω Ω a O Ω a O Ω Ω Ω a O Ω Ω Ω Ω a Ω O Ω Ω Ω Ω Ω a O Ω Ω Ω a Ω Ω Ω Ω Ω Ω O Ω Ω Ω Ω Ω o a td Ω ω > Q td ϋ α Q tϋf tϋ N N B O H t- ti n tii p ω jw ϋ O Ω td a Ω Ω td x to p tO LO CO P P LO CO CO to p to p lϊ l__! !i; tn m D] tn tn ι__ tn ω w tn tn w ^l |κ !Pⁱ . . . ι3 β . . . . . . . 1-3 >A > tA tr' t< tr' tr< i < ' t< ιA ^ •A β H3 1-3 μ. H H M H H H H M H H H H H H C C0 C0 C0 Cn C CO C pd pα pd ?d d pd pd pd pd pd pd •pa pd pd t _¹ __ _ ^ HMH HHHHHffiK X X X K Pd Pd m ω tn ^ » p⁾ ^ ^ ^ p⁾ W a » » P3 ^ g 23 -5 -ϊ ^ 3 ^lO ^l- >H ⁱιJ . 3 ⁱιl it) it) ^tB - iι) i. ⁱt] J=^, ' ^ α - α - ^{^} α α α α d d d pd d d d Ω Ω Ω

H H H H H H H H H H H H H M H H M H H M H H M H H H H H H H H H H H H H M H H M t- H H H M H B H H H H H H H H H H H H H cn cn σ_ cn α-ι cn σ. cn w. cn σ- σ. w. σι σ. wι cn cn cn ch cn cn cn (_n c^ vo so θ Co co oo oo co cn -~ι ~J ι ~o ~J ~J __n -_n cn σι cn cn cn cn Lπ Ln Ln Lπ Lπ oπ Lπ oπ oπ Lπ Ln Lπ Ln L^ P P

~ ~j ~ ~j - ω (). cΛ m σι o. m ι_n σi (_. o -- ~J ~J on on on ~J cn ~J oo ~o cn _n Ln Ln ~J CO CO CO -J CO O --_ C_O S O P P SO to p - Lπ oo Lπ ts3 Lo p cn Lo p p to oo ι^ - c_n cπ ιJ-. p so co -θ -o _n .l^ p -J CD .~J Lo p Lπ ιi^ cn ∞

!O ~J tsJ CX3 S0 L0 P Lπ S0 P ~J cn Lπ 0J CΛ L0 O P P SO ~J Lπ θ O ~J C^ CX) O C0 C0 _0 0π ~J P O P ιl-> P ιP^ ~0 '~J so cn to σ^ C Lπ ~j J so to oo p so P ~J o -θ ιt^ oJ ~J ιi^ cn p co ι__- Cθ Lo p Lπ _o o tNJ Lθ Lo cn o w

CTi cri oπ oπ Ln Ln oπ Lπ Lπ Lπ Lπ Lπ oπ Ln Ln Ln Lπ Lπ Lπ oπ Lπ on Lπ on oπ Lπ Lπ oπ Lπ Ln Ln Lπ Lπ Ln oπ Ln iP- ^ o o ι_o ιo co cn cn ~J cn oo ~j |^ Lπ _. ιf_. on ι)-. oo oπ oo oj oo to p p t p L ι(__. oj p oo to tso p o so oo ∞ c_n Ln tθ ι(~. oo Lπ ~J ιi^ cn o o co oo o oo Lo oπ oo o so Lo to oo tθ ι|_i ιii i_o cn ι(-. _o p ιl-> tθ Ln Lπ cΛ σι tsJ c ~J Lo ιθ - co ~ θ ιi^ ~ o ~o c w ι_^ o so p o -j o ιj^ o c p p ιi^ x3 θ-ι θ θJ θJ J ι^

_n o p p Ln L ιt_. _n co oo p co Ln c. o p p ~ p o cxι Lo o -j so ~j ~ Lπ Lπ _n P co cn ^ ~j p t p p Lπ cx) ^ o -^

PPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPPP ooooooooooooooooo oooooooo ooo ooooo oo oooooσoooooooooooo oo ooooo ooooo oooooooooooooooooo oo ooo ooooo ooooooooooooooooooooooooo oo

~o -j -j ~j ~j co co ~ ~j -J ~ ~j ~j ~j _n _n ~J so so P o so so -o cx) Lπ c_n cn

~j Lo co ∞ p o p o to ~J o αo _Pi _^ o to ~J Lπ _lt-. P ιi~. ιf_- cn Lo co θ P Lπ co Lo _n ~ oo oo ιi^ θ ι(^ o w ιl^ ω p o o fo cn ω ι)__» o oo i-^ o P θ oo J o sD _ p o ιS--. υ. p ι>θ ι!-. o p to _^ cn cn ~J co σι cα cn cn ~ cx) cn cα cn ^ ~J oo on ~J CD cn c_n cΛ ~J C» ^ _n _. cn ~o cΛ

to to to to to to to to to to lis' ti^y ^ to ^ to to to ljy ι- B β ^μ3 B ι-3 t-3 ι-3 >-3 ^μ3 B e ι^β >-3 ι-3 ^β t-a θ ι-3 <- >β ^μ3 θ ^{β β} !-3 ^β B ^β ι-_ ^{β β} ι-3 ι-- B β ι-3 ι^

O O O O O Ω O O O O O O O Ω O O O O Ω O O O O O O O O O O Ω O O O Ω O O O O O O O O O O O O O O O Q O O O Q Q O O O Q Q gggggggggggggggggggggggggggggggggggggggggggggggggggggggggggg

~J -J ~J ~J ~J -J ~J ~J -J ~J ~J ~J ~J ~J -0 ~J -~J -_ -J -~J ~J ~J -J ~^

P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P cx> oo c)θ cx3 cxι oo co co ~ -J - ~ -o ~j ~j -o ~ ~J cn c_n cΛ -J o. Ln ιl-> Lo _sj p o o oo - c_. _n ιf__> co _Nθ p o so _o --_

Ω Ω Ω O Ω Ω Ω Ω Ω a o Ω o Ω Ω a O ΩaOΩaOOΩ Ωa ΩΩOOΩΩΩaOΩΩΩΩΩaOΩOΩΩa Ω Ω a Ω a Ω td α Ω Ω Cd !_=> Ω td Ω OO D.^ t ^α Ω td ! H H to p α p t α to P COΩptd Ht Hp rJOω ■ o n_) n_) irj iti <! < <l <; <; < co co co co co co <; Ω Ω Ω Ω Ω Ω Ω Ω Ω ^l l ^{, ,} ^ t W ^ W n3 τ3 ^lτ) 3 Λ W ω Co ω ω K K W ffi W W pd pd pd pd to to to to to ^ to t. M H M M KI to ≤ >_a £> tr¹ tr¹ tr⁴ tr¹ tr¹ V t¹ tr¹ CΛ CΛ Cn Co Co CO CO CΛ pd ^ pd pd pa pd pd M H H M H H H H H H H H O Ω O -H tH _H _H _^H _H p_) p d _H t¹ _^H t¹ F a a a a a a a 3 W iϋ »τ3 τ3 ¹τ_ι ¹χi ^|xi O O O O O O O pd pd pd pd pd pd t_o to co co co cn

MHHHHM HHHHHHHHHHHHHHHMHHHH HH H MM HHMH HHHHH HHHHH HHHHM HHHH HHHMHM

~j -j -j ~j ~j ~o ~j ~j ~j -~a ~j ~ ~j ~ ~j ~j -j ~ -j --! ~ ~jJ ~~jJ ~~J ~J ~J ~J ~J ~J l -~3 -O ~J -J -J ~4 ~J ~J -J ~J -J ~J ~J ~J ~J -J ~J ~J ~J ~J -J ~J -O ~J ~0 C^

~) θ θ ~l cn m oι σι u. θ- m t_ι uι uι uι uι ui ι^ ιti l)_, l|^ l(_-. ^ OJ OJ J OO LO O OJ OJ L M M t t _O tO CO CO P P P P P P P O O O O O O SO SO SO SO S_o

cn ti_. Ln cn Lπ Lπ Lπ .l^ Ln cπ Lπ Ln Lπ cπ cπ Lπ Ln Lπ cπ cπ Lπ cπ Ln cn Lπ W Lπ ._ri Lπ cn -^ o ι_o p o o o p o o P i ι^ oo _n Lπ _l-. Ln Lo ^ oo σ^ Lπ Lπ Lπ -~j c_n ι(-. cn Ln oπ Lπ Ln cn -l^ Lπ c» M o so to cn Lθ ~J o ιf~.

-j t Lo p Lo oπ m

C _o oo to p p o P so ω

P P P P P P P P P P P P P P P M M P P P PPPPPPPPPPPP P P P P rf5. Lπ θ ιP- Lπ ιp- p tsj co L j__. oθ ιF~ cn π _l-- L Lo oJ o O -J t P P Ol Ul Ul i^ l tO P O O P O O - SO LO -J O -J o tn ι_i (Λ Ui ω ω f, ι_ t - θ o o o

-j L oo ^ -j - vo M s -θ Lo ₁i^ p - - oo --α ∞ oo Lπ _o so ιo tθ Lπ Lθ ιt^ - ι{-- o θπ o p *> ω o uι uι a) Mo to p uι ω «) p uι i) (iι j (rι ω -J P - M j (_>

P _ Cnn bιt^ ^μP ^j-J ^μP nθ lLnO Jι_i_,. OO I.O- U- _.. σ.ι. σi μ (O O ^ m p O W lD ιl- W W P J Ol O l . ts-o s _o oo to p p cn o o rf-. co o -J oo cn oπ o o o Lo o on -j p s_o oo t so so o ιl-. oo co co -J cn J cn Lπ p oo oJ P tO SO ι(^ O ιl^ ιt-. P ιI-. P CO tO -j p θO ιt-- C L t C --_l p ω «- P t ιo ι» uι oι tD θ θ _i σHJ - θθ ι|i. o cn si w θ p

P P P P P P P P P P P P PPPPPPPPPPP PP PPPPPPPPPPPPPPPPPPPP PPP PPPPPPP ooooooσoooooooooooooooo oooo o oo ooo oooo oooooooo o o o o o o o o o o o o o o o ooooooooooooooooooooσoooooo oooooooooo ooooooooo oo o o oo o oo o o o oo

Lo ω ι|_i ||-> ιf-. ι{-. |P-. |(_~ .f_- ._-> .J-> |i-> .!-» ι|-» ι|-- !j-- -J σ-ι C^ c. c_n cn _ c^ _^ -j _^ _. <-n cn cn c_n cn cn cn -j - -j -j cn -J -J -o -J -J -J -J -J -J iO P p m i ui L. _^ ii |i Ui _ji _J iii Ui a) p p u tO - ^ J o o o p so cn oo co ⁾ tθ ιf-. u_ι __o so cn Lπ Lπ -j -j so so o o p θJ Co co p co cn cπ _π -J _l-» cn σ. cn ι(-- θ so o c» to co oj -J CD so oπ so _o θo o ι)-> ι)^ p o co o -n -j so p Lπ -J Lo on Lπ Lo -o _. p oo cnso ω

_ιmuι P co p ωto p m _) ^piD σι _ uι*. σι oo5o^ «ι. frcA- _im (Λicαj - ιo ι^ ui -3 ω

(_n c^ -j -θ _n <__Λ σ\ _^ wΛ -j co _ri co cn cn -o co c _n _^ _^ _. - oo c^ -o co _

-__.

ATOM 7188 CG PRO E 77 57, .736 51, .362 13. .981 1. ,00 41. ,25 6

ATOM 7189 C PRO E 77 59. ,407 48. .464 15. ,456 1. ,00 39. .33 6

ATOM 7190 O PRO E 77 59. ,766 47. 848 14. ,457 1. 00 39. .91 8

ATOM 7191 N ILE E 78 59. ,368 47. ,929 16. ,665 1. 00 39. ,53 7

ATOM 7192 CA ILE E 78 59. .729 46, .550 16. ,938 1. .00 39, .36 6

ATOM 7193 CB ILE Ξ 78 59, .440 46, .235 18 .408 1, .00 41 .90 6

ATOM 7194 CG2 ILE E 78 59. .421 44. .753 18. .667 1. .00 44. .69 6

ATOM 7195 CGI ILE E 78 60. .512 46. ,887 19, ,259 1, ,00 45. .61 6

ATOM 7196 CDl ILE E 78 61. .904 46. .569 18, .783 1, ,00 45, .82 6

ATOM 7197 C ILE Ξ 78 59, ,002 45. ,562 16. .048 1. ,00 39, ,58 6

ATOM 7198 O ILE E 78 59. ,556 44, .550 15. .645 1. ,00 39, .79 8

ATOM 7199 N SER E 79 57. ,755 45, ,870 15. .729 1. ,00 41, .50 7

ATOM 7200 CA SER Ξ 79 56, .932 45, .011 14. .891 1, .00 41 .99 6

ATOM 7201 CB SER E 79 55. .497 45, .502 14, ,931 1. .00 40, .86 6

ATOM 7202 OG SER E 79 55. .441 46. .876 14, .633 1. .00 44. .60 8

ATOM 7203 C SER E 79 57. .370 44, ,887 13. ,441 1. .00 43. ,24 6

ATOM 7204 O SER E 79 56. ,883 44. .020 12. .730 1. .00 43. ,62 8

ATOM 7205 N SER E 80 58. .278 45, .750 12 .996 1, ,00 44 .61 7

ATOM 7206 CA SER E 80 58. .751 45. .713 11. .619 1, .00 44, .15 6

ATOM 7207 CB SER E 80 58. .841 47, .133 11, ,062 1, .00 43 .26 6

ATOM 7208 OG SER Ξ 80 57. .568 47. .744 11, .017 1. ,00 47. .92 8

ATOM 7209 C SER E 80 60, .110 45, .033 11, .482 1. .00 45 .19 6

ATOM 7210 O SER Ξ 80 60. .661 44, .963 10 .387 1, .00 46 .20 8

ATOM 7211 N LEU E 81 60, .645 44, .533 12 .589 1, .00 42, .25 7

ATOM 7212 CA LEU E 81 61, .949 43. .891 12, .577 1, .00 42, .76 6

ATOM 7213 CB LEU E 81 62. .950 44. .702 13, .400 1, ,00 41. .44 6

ATOM 7214 CG LEU E 81 63. .144 46, ,190 13. ,150 1, ,00 39. .51 6

ATOM 7215 CDl LEU E 81 63, .861 46. .826 14, .314 1. .00 38, .48 6

ATOM 7216 CD2 LEU E 81 63 .908 46 .367 11 .891 1, .00 43 .00 6

ATOM 7217 C LEU E 81 61, .846 42. .530 13, .216 1. .00 42, .93 6

ATOM 7218 O LEU E 81 60, ,845 42, ,221 13. ,865 1. ,00 47, .16 8

ATOM 7219 N TRP E 82 62, ,880 41. .715 13, .028 1. .00 39, .63 7

ATOM 7220 CA TRP E 82 62. .925 40. ,412 13. ,657 1. ,00 38. .60 6

ATOM 7221 CB TRP E 82 63. ,872 39, .465 12, .941 1. .00 37, .23 6

ATOM 7222 CG TRP E 82 64, .186 38, .241 13, .753 1. .00 39, .34 6

ATOM 7223 CD2 TRP E 82 65 .272 38, .087 14 .678 1. .00 41 .49 6

ATOM 7224 CE2 TRP E 82 65, .142 36. .811 15, .266 1. .00 40, .40 6

ATOM 7225 CE3 TRP E 82 66. ,344 38. ,909 15. ,071 1. ,00 41. .39 6

ATOM 7226 CDl TRP E 82 63 .469 37. .086 13 .814 1, .00 37 .83 6

ATOM 7227 NEl TRP E 82 64 .032 36 .222 14 .719 1, .00 40 .75 7

ATOM 7228 CZ2 TRP E 82 66 .044 36 .335 16 .228 1, .00 39 .91 6

ATOM 7229 CZ3 TRP E 82 67, .237 38, .436 16, .025 1, .00 38 .98 6

ATOM 7230 CH2 TRP E 82 6 .080 37 .161 16 .591 1, .00 40 .84 6

ATOM 7231 C TRP E 82 63, .513 40. .766 14, .999 1. .00 38 .10 6

ATOM 7232 O TRP E 82 64, .356 41, .636 15, ,086 1. .00 39 .18 8

ATOM 7233 N VAL E 83 63 .068 40 .104 16 .049 1, .00 39 .36 7

ATOM 7234 CA VAL E 83 63 .578 40 .395 17 .367 1, .00 38 .27 6

ATOM 7235 CB VAL E 83 62 .562 41, .277 18 .141 1, .00 39 .12 6

ATOM 7236 CGI VAL E 83 62, .919 41, .352 19, .596 1, .00 43 .60 6

ATOM 7237 CG2 VAL E 83 62, .557 42, .678 17, .565 1. .00 38 .09 6

ATOM 7238 C VAL E 83 63 .853 39 .081 18 .089 1 .00 37 .11 6

ATOM 7239 O VAL E 83 63 .154 38 .098 17 .896 1, .00 39 .80 8

ATOM 7240 N PRO E 84 64 .909 39, .039 18 .899 1, .00 35 .89 7

ATOM 7241 CD PRO E 84 65 .921 40 .088 19 .075 1, .00 38 .94 6

ATOM 7242 CA PRO E 84 65 .276 37 .842 19 .651 1, .00 35 .46 6

ATOM 7243 CB PRO E 84 66 .485 38, .306 20, .456 1. .00 36 .52 6

ATOM 7244 CG PRO E 84 67 .087 39 .306 19 .600 1 .00 37 .91 6

ATOM 7245 C PRO E 84 64 .134 37 .398 20 .555 1 .00 36 .04 6

ATOM 7246 O PRO E 84 63 .541 38 .220 21 .246 1 .00 34 .75 8

ATOM 7247 N ASP E 85 63 .839 36 .103 20 .565 1 .00 33 .87 7

ATOM 7248 CA ASP E 85 62, .771 35, .595 21, .400 1, .00 35 .26 6 CD en en IV) O en o en 4^ oo oo IV) o en σ en o en en to to to to to to to to to to ;p to > ; to ;μ ;> to to to to ' ;)_d to

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_» ∞ m ∞ ∞ ∞ ∞ ∞ ∞ -o -o -j -j -J -j σι cn cn cn cn cn c^ _. σΛ _^ Lπ _π cπ Lπ Lπ Ln Lπ Lπ

-j -o -o -o -o - -j -o -o -o -J -o -j -J -J -J -J -o -J m cn -o cn cn -n _^ _^ cn cn c_n cn cn cn cn cn to on cn ιi-. co oo oo oo oo oo ιi__. Lo _lt-. ιP. Lo p o o c_3 so c_o o so so so cn cx) -J v_-. ιfs. Lπ Ln _^ ιo p o so -J rfs. D Co σι P rf-. cn o to to so -o oo o o -θ rfs σι o. Lπ oo o -J cn oo p cn o o cn oo rf_. Lθ cn P ω ιl-> oo rfs. -^j rf-> σΛ θ o p Lo so so ∞ cn P o -J θ cn cπ so - - cπ ω -^j so Ln so - p - ιjs. ω -^j cn ω -^ ts^j o Lπ ω so ι_o to -^j p -J P o co OT C» oo Lπ p oo ω ∞ .-^j t_o .fs. θ P _. rfs- ι|s> P -NJ cn -^

-o ω to to to to to to to ω to -o to to to to to ω to M to ω to to to to to to ω ω ω ω u ω M to to to to ω to to to to ω ∞ o to t ω ^ ui i -j m -o oi J -J -j αi si ^ ^ ii iji ui w σi ^ - CD O p p o o o co io j ω oj o iii co iD Co -i ∞ iD m co . o αj ω o p o p o p p p cn co cn o p cn J o _ o . m .. - _ i p ffl t fc oi si o P ^ o ω co ^ p ui ic co j μ oi t iD μ t i D μ tD ui iji μ - ui iii t oi is. o αi m o o ^ f' U tJ oi oo αi Lo oo on -j to to oo -J Lo cn co LO --JJ ccnn L_ππ ,p s—o o t ιi-. p -^j oo t on tJ P oo cπ ι(s. cn cn -J cπ ιo -j to -J cn co - ιi__. α_⁾ ι|s. to P OT

SD O -0 0 -NJ _ -O tO CO CO -O O CO ιp. -O l_O Cπ CO -J iji P KJ ω J oi -j ω ω -J i i σi to iD tΛ W tii ^ ^ ui ^ ω -o P o m σi iD Co iii i J tJi ϋi σi -i oi σi -j

P p p p p p to p p to μ P -J W _O IO M _ t- - M IO _O IO _ι) _O W W - tO IO on -J cn -J oo so o so so o so o o p -o oo co co - on rf_, -j cn cn ιp=. ιt-. ι(s, oo rf__. co p oo σι W ι_s. υi -θ o tθ Lo o _o co ∞ ι!-. Lo -j so rfs.

^■-J rfs. Lπ t p Lπ

P P P P P P P P P P P P P P P P P PP P P P P P P P P P P P P PP P P P P P P P P P PPP P P P P P P P P P oooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo oooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo

Lπ oo ∞ ∞ oo -j -J cn cn Lπ cn cn c_n σi -! w^ Lπ Ln cπ Lπ Ln Lπ Lπ Lπ Lπ Ln Lπ Ln Lπ ι{-» rfs so cn -J cn Ln so ιP. σι o so o o p o o o Lo co - _o co Lπ cn cn -j Lπ o p o cD -J so Lo so o cxι σ^ _n o t tθ ιi^ c^ cn 00 P -J o L0 L0 t t P LD C0 O cn ιP» -J __s. 0J O P M 00 O 00 l ι Ln L0 O S0 C» _NJ -J P O ∞ to -j Lo cn o -_ -4 oo Lo o -J rfs. - so cn Lo -j o oo co -j cn cπ cn -J P Ln C Co so co rø cn -J -J cn -J cn.cn cn cn -J C» cn oo cn cn -j cn cn -J cn -o cn cn cn cn -J co cn -J cn -J o-ι cn cn cn -o c» <_n cn ∞

ATOM 7737 O ARG E 148 73.418 28.,564 14.,766 1.00 58.11 8

ATOM 7738 N GLU E 149 71. ,836 28. ,707 16. .384 1. ,00 58. .68 7

ATOM 7739 CA GLU E 149 71. ,067 29, ,756 15. ,716 1. 00 56. ,72 ^■ 6

ATOM 7740 CB GLU Ξ 149 69. ,598 29. ,337 15. ,630 1. 00 55. ,99 6

ATOM 7741 CG GLU E 149 69. ,435 27, ,854 15. .335 1. ,00 57. .25 6

ATOM 7742 CD GLU E 149 67. ,992 27, .402 15, .239 1. .00 57, .65 6

ATOM 7743 OEl GLU Ξ 149 67. .166 27, .825 16. .075 1. .00 58, .97 8

ATOM 7744 OE2 GLU E 149 67. ,684 26, .606 14. .332 1. .00 56, .32 8

ATOM 7745 C GLU E 149 71, ,214 31, .073 16, .463 1. ,00 55. .95 6

ATOM 7746 O GLU E 149 71. ,423 32, .122 15. .852 1. .00 54. .41 8

ATOM 7747 N ILE E 150 71. .109 31 .012 17 .787 1, ,00 55, .27 7

ATOM 7748 CA ILE E 150 71. .265 32, .202 18. .600 1. .00 54, .72 6

ATOM 7749 CB ILE E 150 69. .922 32 .686 19, .227 1. .00 54, .60 6

ATOM 7750 CG2 ILE E 150 70. .190 33 .711 20 .339 1. ,00 51, .29 6

ATOM 7751 CGI ILE Ξ 150 69. ,051 33, .354 18, .167 1. .00 53, .90 6

ATOM 7752 CDl ILE E 150 67. .738 33. .855 18. .709 1. ,00 52. . 06 6

ATOM 7753 C ILE E 150 72. ,238 31. .954 19. .728 1. ,00 55. ,47 6

ATOM 7754 O ILE E 150 72, .226 30 .898 20. .361 1, .00 54. .39 8

ATOM 7755 N SER E 151 73, .083 32, .948 19, .962 1. .00 56. ,26 7

ATOM 7756 CA SER E 151 74. .055 32, .898 21, .035 1. .00 59, .09 6

ATOM 7757 CB SER E 151 75. .478 32 .752 20, .471 1. .00 59. .25 6

ATOM 7758 OG SER Ξ 151 75. ,826 33, .853 19, .653 1. .00 59, .55 8

ATOM 7759 C SER E 151 73. ,904 34, .226 21, .770 1. ,00 59, .98 6

ATOM 7760 O SER E 151 73. .793 35, .283 21, .139 1, .00 59, .94 8

ATOM 7761 N VAL E 152 73, .878 34, .172 23, .096 1. .00 60, .88 7

ATOM 7762 CA VAL E 152 73. .739 35. .380 23. .900 1. ,00 62. .73 6

ATOM 7763 CB VAL E 152 72, .628 35, .233 24 .956 1. .00 61. .31 6

ATOM 7764 CGI VAL E 152 71, .339 34 .777 24 .294 1. .00 58 .78 6

ATOM 7765 CG2 VAL E 152 73, .067 34, .241 26. .034 1. .00 62, .59 6

ATOM 7766 C VAL E 152 75, .054 35, .633 24, .612 1. .00 64, .27 6

ATOM 7767 O VAL E 152 75, .743 34 .687 24, .994 1. .00 63, .76 8

ATOM 7768 N ASP E 153 75, .393 36 .904 24 .805 1, ,00 66, .67 7

ATOM 7769 CA ASP E 153 76 .650 37 .261 25 .456 1. .00 70 .32 6

ATOM 7770 CB ASP E 153 77 .713 37 .471 24 .381 1, .00 70 .77 6

ATOM 7771 CG ASP E 153 77. .832 36 .272 23, .433 1. ,00 74, .19 6

ATOM 7772 ODl ASP E 153 78, .483 35 .261 23, .803 1. .00 75, .87 8

ATOM 7773 OD2 ASP E 153 77 .265 36 .331 22 .319 1 .00 73 .45 8

ATOM 7774 C ASP E 153 76 .531 38 .533 26 .304 1, .00 72 .18 6

ATOM 7775 O ASP E 153 75 .835 39 .481 25 .922 1. .00 72 .90 8

ATOM 7776 N PRO E 154 77 .187 38 .561 27 .478 1, .00 73 .33 7

ATOM 7777 CD PRO Ξ 154 77 .671 37 .398 28 .243 1 .00 72 .54 6

ATOM 7778 CA PRO Ξ 154 77 .123 39 .755 28 .332 1, .00 75 .06 6

ATOM 7779 CB PRO E 154 77 .749 39 .279 29 .642 1, .00 74 .00 6

ATOM 7780 CG PRO E 154 77 .389 37 .823 29 .676 1 .00 74 .05 6

ATOM 7781 C PRO E 154 77, .911 40 .901 27, .688 1, .00 77, .63 6

ATOM 7782 O PRO E 154 78 .502 40 .717 26 .^'620 1, .00 78 .05 8

ATOM 7783 N THR E 155 77 .940 42 .066 28 .338 1 .00 81 .26 7

ATOM 7784 CA THR E 155 78 .638 43 .230 27 .781 1 .00 85 .03 6

ATOM 7785 CB THR E 155 77 .623 44 .147 27 .020 1, .00 83 .83 6

ATOM 7786 OG1 THR E 155 76 .717 44 .749 27 .956 1 .00 81 .33 8

ATOM 7787 CG2 THR E 155 76 .815 43 .341 26 .020 1 .00 83 .47 6

ATOM 7788 C THR Ξ 155 79, .417 44 .101 28 .803 1, .00 88 .40 6

ATOM 7789 O THR E 155 79 .900 43 .592 29 .825 1 .00 88 .82 8

ATOM 7790 N THR E 156 79. .527 45 .405 28 .487 1 .00 91 .48 7

ATOM 7791 CA THR E 156 80 .206 46 .443 29 .288 1 .00 93 .55 6

ATOM 7792 CB THR E 156 79 .615 47 .854 29 .002 1 .00 93 .31 6

ATOM 7793 OG1 THR E 156 79 .697 48 .136 27 .596 1 .00 92 .71 8

ATOM 7794 CG2 THR E 156 80 .376 48 .925 29 .813 1 .00 92 .25 6

ATOM 7795 C THR E 156 80 .165 46 .249 30 .803 1. .00 95 .69 6

ATOM 7796 O THR E 156 79 .173 46 .584 31 .476 1 .00 95 .92 8

ATOM 7797 N GLU E 157 81 .264 45 .733 31 .340 1, .00 97 .89 7 CD en en 4^ oo oo ro IV⁾ O en o en o cn o en o en o en to to to to to to toto to to toto to to to to to to 3 ^ β 3 ^ H β β ^ ^ β ι-3 3 β β B ^μ3 β β 3 β '-3 3 β β ^μ β B ^ β β 3 ^μ3 3 >-3 ι-3 B β

0ΩΩO0OOΩΩOΩΩΩΩΩΩ00ΩΩOΩ0ΩOΩΩΩQΩ0ΩΩΩ0ΩΩΩΩΩΩΩΩΩ0Ω0Ω0OΩ0ΩQΩ0QΩO0 ggg gg ggg g g ggggg ggg ggggg gg ggg ggggggg gggg g gg g gg ggg g gggg ggggg gg

-_ - -J -J ! -- -- -J -J -J oo oo co oo co co co oo co co on Ln _n on cn cn Ln on cn iis.

03 --J C_n L_n ιl-. 00 M P O SO

ΩΩΩΩΩΩΩa O Ω O O Ω Ω Ω Ω a O Ω Ω Ω Ω O Ω Ω

H α H α Ω H H O Ω d ^<£> o Ω o Ω ΩΩΩΩaΩΩOOΩΩΩa Ω ω Ω > a OΩO α D Ω ω α α Ω ω u* Ω dd $ a H H t Ω td t CO P P ω ; CO p to p t P α o Ω Ω Ω a O Ω O O Ω Ω t α p Ω ω to p

. . . . . . _ . Q θ n Q Q O O O O to _ tn tn to tn ' ^ l l» l ^ ^ l ^ tn [θ ln t» (θ [n ^ ^ i> Q O Q O κ| ^ ι κi ι<; ι- ι κ; t→ i' irⁱ ι→ ι→ _rⁱ t^H |r^, _r^, H M H H H H C M o w o cn o co co c M d d d pd ^ pti q G α G C α G W pd pd d pd iϋ n_ ^ . ^fι3 ^

H H H H H H H H H H H H H H H H H H H H H H M H H H H H H M H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P

Ul Oil Wl Wl Wl Wl Ul Wl Ul Wl Ul Wl Oil Wl Wl Ul Wl Wl Wt Wl Wl Wl W μ μ μ o o o o o o o o O S- S-0 S- ωS0 iSOD iSo0 C_i0) C0θ0 0_o0 t0D0 cCo0 (0_0j c0o0 D00 J-- --Jι -Jι --0. -Ji s-Ji --.. -

-J -J -J -J -J — J — _ -J -J -J -J — J -J — J --o-J -J -O - -J -J -J -J -J OO OO O O OO O CO OO OO OO OO OO OO OO OO CO O

CO P CO tsO p o o to tsJ co cn -- cn Ln Ln ∞ 00 SD C0 S_0 C0 00 L0 O P P rfs. Ln rf-. -0 tO C P P C ll-. 00 t CO co o tsj o oπ oo co ) rf_s. L ω Lπ OO OO OO rfs- tO P CO O cn Ln rf , Lo ao Ln ifs. p -J o p co L Lo oo M _ _ tsj cπ cn p to co co io cn c rf-. o o -J cn on co P Lo co oo ι|s. CD -j co cn cn on rfs. oo Ln o p LO -j co Lo to oo p a

Cji Lπ oπ on cπ cπ oπ cπ cn Lπ Ln on θπ Lπ θπ oπ oπ Lπ Ln Lπ oπ on oπ rfs. ||:_. rfs. ||s. rf^ ι^ ιis. on oπ Lπ Ln Ln on Lπ L^ Ln oπ co oo rf^ co rf^ rf_. cn Ln cn ι Lπ rfs. on rf^ co ιi__. oo M P P P o o _n OT _n oo ι_o o p p -θ ιf_. oo ω

^[ι> _- w p^■p N) tn ι _- ι o fc p μ U l o p cn Lo o p co so rfs - on

LH L0 1_0 P l__) Cn θ CO Cθ p rf-.

0J CO CO LO L0 0O to ω M W _.j-» Lπ rfs. on C ii__. o tsJ

-o cn cn oJ on co p so P -J P on p p p p p PPPPPPPPPPPPP PP PP PPPPP PPP PP PPP P P P P p P P P P PPPPP PP O O O O O O O O O O O O O O O O Ό O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O

P P P P P P P P P P P cc^^ccnncc..ccnn __nnccnn __nnccnnccnn ^j s^j iΛ ^ ^ ^ ui ^(jι ^ m t o μ o ∞ i- θ o ^ ui ι_ι ω P

-j co cn -J oo rfs. σ co ω

CO P LO NO p o M rf-. p cn cn cn cn cn cn cn -o oo σi oo ao σ_. t_.n cn cn -J Co cn -o c. cn -J ∞ tΛ -O co cn c^ m

CD en en 4 4^ oo oo ro IV⁾ O en o en o on o en o en en to to to to !)y !w ;! !_y to !b' to to to to to |y to t_y to ι-3 ι-3 !-3 ι-3 >-3 t-_ ι^ B B β H_ .-3 β H i^ ⁽^ β r3 3 β r3 '-3 3 '-3 '^ H !^ β >^ ι-3 ι-3 β '-3 >-3 i^ β

ΩΩΩOOOOΩΩΩΩΩΩOOOΩOΩΩΩΩOOΩΩΩQOOΩΩOOΩΩΩQΩOΩΩOΩΩΩΩOQΩΩΩΩQΩOOΩΩO gggggSggggg gg gg ggg ggggg g ggg g gg g ggg g ggggggggggg g ggg ggggg gg ggg

-J -J -0 -J -J -J -J --J -0 -J -J -J -J -J -J -J -0 -J -J --3 -J -J -J -0 -0 -J -J --J -J -J --J -0

P P P P P P P P P P O O O O O CD O CD O SO S-D SO '-J SO SO S S SO SO CO CO CD CO CO OO O CO CO OO -O -J -O -O -J -O -J -O ^ so co -J c_n L_n rf_. L to p o i_3 Co -J cn on its. oo to P o so cx) - cn Ln i|s. oo to p o Lo oo i cn on i^ -o

Ω a Ω g a a Ω Ω Ω a ΩΩOΩΩaΩΩΩ Ω Ω Ω Ω Ω a Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω a Ω Ω O M K N H tl Q til ^ Ω dd X ΩΩΩΩΩΩΩΩaΩΩaOΩΩΩΩa t. α t. o ω M H θ Ω O tB N H M ϋ ϋ fl tU ^ W t p C co p p co p t p to p

. . ^ ^l ^ |ιs ^ ^l ^ ' [o tβ tn to [n to . . . . . . . . . . . . Q Q Q θ Q Q Q θ Q tn [n tn [» [n ω . . . . . . . . . ^μ3 B

W ffi p ;Λ pd .« p p :_d pd :Λ H H H H H H : κ; κ; _- ; ! κ; κ; ; ι^ κ: κ; t^ϊ _^

H H Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω pd pd pd pd ^ pd pα pd pd ^ pd pd pd pd td pd pd pd ≥; a a a a a a a a iΛ pd pd pd pd td H H H H H M H H H H H ?c( pd fd M H H H H H M H H H H H H H H H H H H H H H M H H M M H H H H H H H t M M H H H H H H H H H H H H H H H H M H H H H H H PPPPPPPP PP P PP P P PP P P P P P P P PP P PP P PP P P P P

-j -J -J -3 -J -O -J -J -_ - -o -j -o cn c_n σ> cn c_n cn

P P O O O O O O o o o o o so so so so ι__ι So

cn cn cn cn cπ Ln Lπ cn cn cn _n _n cn _n cn _n o-ι _n c^ _. cn σ cn _rι cn cn m σι cn _^ -j Ln cn on so so i_o o C rfs. on iis. vis. i rfs. i|^ L i(s. Ln its. rfs. rf^ rfs. rf^ O O i^ Ln -o c^ o c» co Lo -J θπ rø Lθ ι^ oo oo o oo c_n __n o P oo - p o ι^ ιo -o P cn p rø Lo Lπ cn p oo o -o p L_π Ln so rf^ p oo - rf__. α) -o so o oo oo cn -J -θ Lo α3 rfs. -D α3 θo L -o oπ t p so t o co so Ln p so c» oo so LD rf-. _^ p co oo to rfs. -j -j so OT Co so oπ Lπ _n cn _π p - on p to ∞ so P θ on t p o o oo σ^ o so oπ αo so -o ___π σι C ι^ ι(s. cn cn Ln __s. ι__. ι(s. ι|s, L_n Lπ Ln Lπ oπ on on Lπ Ln Lπ θn on Lπ σ^ cn _^ _n c^ Lπ on Ln Lπ on Lπ θπ _^

- O o o -O K ffl iD o μ o μ p w w o M ω ^ iJ iJi - p μ o o tD . oi oi m m H p o io ffl si σi ^ iΛ tji ^ ui ^ ui fc - μ io μ o p w u ω ^ ^ in w ω on p σi i^ ω - ω Ln ijs. co w -o oo P o its. tNJ ii. m Lπ w o cn rf^ -o ∞ o ∞ tø cn P Co cn c_n ^ o c» oo cn cn o ii-. M M o cn so -o oo -J p so o -J -J OO M cn -J LO Lo i oo _o co _n W

_n Lπ rf-. L θo rf_i oπ tsJ Lπ P CD j-. rfs. Ln cΛ -o -J Lo ι__ι co o oπ o rfs. - to so on o -J tsθ Lπ rfs. rf^ rfs. rfs. Ln js. Lπ rf_. Ln Lπ L_π Lπ rfs. ,ι__. rfs. j__. rf__. rf__. ι:. _|i__. rf_i ₁ι^ rf . rf__. |^ ₁|^ _|^ co oo o so o co o o o o so ι_o co oo - cπ Ln cn Ln -θ -n _^ ι|s. oπ σι Lo oo υι oπ cn LJi cn Ln -so rf^ Lθ Lθ ιis, rfi rf-. rfs. cn Lπ cn so p so Ln -o so cπ p p Ln Lπ to p ∞ P ils. p Ln -o tO Lπ Lo W cΛ p p -j Lπ o o tsJ cn -o oo rø so ) C c o co _n cn p o p n oo _ -o [ _π θ ι|s. ι!. rf_i μ-ⁱ Lθ j θ Lo Ln θ ιl-> ω ω oi vi ^ ⁽Λ P M ^j _i w o μ t i ^ -o μ ιo μ ^j - oι (D p ω ιo ιo p u o t o ιι u p ω M ^ ω ^ u i oD _^ oι o i- ji ^ o w (j\ J oi - _i tπ P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P p p p oσoooooooooooooooooooooooooooooooooooooooooooooooooooooooooo ooooooooσooooooooooooooooooooooooooooooooooooooooooooooooooo cn _π cn _n -J cn . _n cn Cπ Ln Ln Lπ cn Ln cπ cn cπ U cn cn _n cn Ln cn Ln Ln ι_n Ln Ln c^ co rfs. -o c_n P CΛ Co -j oo so -j α c ιls. ιt^ o co oo p co J so --J Ln t cn ι_s. oo Lo oo rfs, <3-ι -j co -^

O P JS. ||-. l_s. O C0 C» l_P P Ln CO L0 σ^ 0 ι^ CXI L0 1 ) ιIs. cn 00 t0 Ln θ θ 00 C0 So P ι_s. l ι tO ιl_. 0^

_n cn p L Ln Lπ so o L θ Ln J Lπ -J (xι o U3 j-. Lo oo on c_n o co uo p -J -J oπ co -J p p cxι ₁ιs. o p p c» cn σι Cθ cn o^ c_n -J rø σ. -J i -n ι _n cn cn cn -J co cn c_o cn cn -J co cn oo o. _n _n _n _n cn _^

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. . . . . . . . . . . . . _ . . . . . . . . . . . . . . _ . . . e . . . . . . . . . . . . . . . - . . . . . . . - . . .

ΩΩΩOOΩOΩΩΩΩΩΩOΩΩΩΩΩΩOΩΩΩOOOΩOΩΩΩΩΩOΩΩΩΩOΩOOΩΩΩΩΩOOΩΩΩΩΩQΩΩΩΩ gggggggggggggggggggggggggggggggggggggggggggggggggggggggggggg

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SO SO Q So l_3 S so Sβ O SO lO O S0 1_-> sO I-θ ω l_} l_3 SO I-β O tø SO sO I£> s^ co -o -J -o -J -J -J -J -J -J -J c_n c_n cn _n cn c_n c^ c^ c. _n _n Lπ oπ on L_n Lπ o^ o ι_o co -j cn _n _l^ oo to p o so co -j cn Ln ι^oo w p o Lo oo -- _^ υι rfs. c_o co p o ιθ -θ -- __rι Ln ιjs. oo w

ΩO ΩΩ Ω Ω Ω Ω td Ω a O Ω Ω a Ω Ω Ω Ω Ω Ω ΩΩΩΩΩΩΩaΩΩΩΩΩΩΩa Ω Ω Ω Ω Ω Ω a ΩΩΩΩΩΩΩΩa ΩΩΩΩΩΩΩΩ

QQM Ω N M H D O Ω t p to Ωp H t D a Ω Ω totP)OMi» OCO PO Ω td p p CO ω w Hco Mp O Ω td to p to p ιa Q Ω Ω (D - . . . . β . <; <; < ^ ^ι >' >' >ι ^ι t^ι t t^, t^| i_ f lr¹ t_^H H H H H H H H P Ω Ω Ω Ω Ω Ω Ω Ω Ω ^tw ^fϋ n_ n. iτ) ⁱϋ n3 n_) t¹ t t^, __< lr^l ffi K t5 K K ffi lι! ' p ^{l (}n [n ω [n [o oι θ] W M t. t. t. t. H H H t¹ _r^{, H} _^H _^H |r^, t lr¹ t¹ lr^, _r^, lr^H l^ t^H _^H _^H _^H ffi κ K W ffi W W -i! - ^"t^^{' "}a d p P- Pd pd pd b t¹ E^H v tr¹ _^H hd 'Td ic.l nj 'ti na na nd C^ - α ^■ α ^{■ J ■ '} c^ α M H H H H H H H c.i α C α H H H H H H H H

M H H t_ H H H H M K H H M H H H H H H H H H M H H H H H H H H M H H K. H H K H H H H H K H H H H H H H H H H H H H H H H

P P P P P P P P P P P P PP PP PP PP PP PP P P P pP pP PP PP P PP PP PP PP PP P P P P P P PP PP PP PP PP PP PP PP PP PP PP P P PP PP PP PPP PPP PPP PPP PPP P P <1 -J -J -J -J -0 -J -0 -J -0 -J -J --jJ --jJ --0o --jJ --j0 --j0 -J -J -J --0J -.-0J -.-0J ---J_J .-0 -0 .-_1 -.00 --0J —) -J

∞ ∞ ∞ ca oo -j - -j - - -j -J c^ c_n _^ cn cn cΛ cn ._jι cn cn Lπ Lπ Lπ Ln Lπ rfs. ι_s_

^■J -J -J -J -J -J -J -J -J -J -O -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -^ ιts. Lπ cn _. -o _n cn so -J ∞ -J c -o σ^ ι_s. ι!_. _n Ln c_n Ln cn so so so c_o --j cn -J C Lπ L^ o co p c»

_π rfs ,|__. LO L _OJ CO L_{O |}IS. Lθ ω ιJ--> rf--> rf-. ,|_-> ι)S. rf__i rf^ rf__, ||_i rf_» ,^ ,|_i ,^ ,^ rf__{i |}|^ p p o _o so so so o oo so o p Lo co rfs. oo ιi_i Lo _t-. oo Lθ to rfs Lo o j_!. oπ cn cn cn ι|s. υi Ln cn cn co -j so p -J _o cn t -o cn so -j cn -|s. Lo cn so Ln to Lo o io D i_s. cn cn so -j p -J O Ln o to p oo on -j -j M o c» ιls. cn cn o — j c_n oo so -J o on so o tsj oo tθ ιi-. so _n -J o -J io -J o co ι_) θJ p cn -J cn _n Ln c^ ∞

P -J lP^ p l_5 M CXl -J I» __s. p -J iI-. C0 tO il-. 00 S0 _I^ P O -J O C0 S0 tO t -J 0J C0 00 t cn O 0n t>J O 0J ^ CO 0 CO CO CO C0 C CO C CO CO 0O CO LO LO CO C 0 J_. rfS, ,t__, rfS, rf__> ,|__. rfS, rf__, ,|s. |J__ J__^ to oj oo j__. oπ σ^ cn co o oo -J oo co co so - co so o to p p p p co to θJ ιP- rf-. cxι oo cxι cn cn LJi L_π oπ p M rfs. ι^ o p p co vt^ o o p co to o oπ cπ rf-. cn rfs. Ln w co co p so p -_] so rfs. -J oo so o ιo o LJi Lθ M _o - c_n to ∞ σι ιI^ ω -o - p tsj Lθ rfs. rfs. σ cn -J ιts. ω -j rfs. -j |sj p o tsJ Lo cn ι_-. (_n -J CD σι so o^

^ l Ln Lo oπ Lo o ∞ P Co io ui oo p -J so oo -j o cn Co p co p oo co LD O o cn to cn co o cn to ui cn io -^

P P P P P P P P P P p P P P P P PP P P P P PP P P PP P P P P P P P P P P P P P P P P P P P P P P P P P P σ o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o σ o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o σ o o

-j - -j -j -j -J - -j σ^ cn so -j cπ ιts. oo ιθ !θ o CD So

Lo -j ι/s. o - ι)s. o NJ θo oι c» oo co oo ci. p -J Co cn to on c_n σ^ cΛ θ. -J co σ^ c_n α3 c_n cn -J co cn cn cn cn cn -j αo cn (Xι oo o-ι c_n cn -j co cn cn c^

CD en en 4^ co oo ro ro O en o en o cn o en o en en

;_> to ^| to !_y ; ;_-=< ;_^y ;_5' ; ' to to to ι-3 ι-_ β >-3 ι-3 3 β β ^β ι-3 β ^{β μ}3 ι-3 β ^β ιβ β ^β !^ ι-3 !-- i-3 β !^ >^β ι β !- ^β ι^ 3 ^β t-3 ι-3 ^ β 3

Ω Ω Ω Ω Ω Ω Ω O Ω Ω Ω Ω Q O Ω Ω Ω O Ω Ω Ω Ω Ω Ω Ω Ω O O Ω O Ω Ω Ω O Ω Ω Ω Ω Ω Ω Ω O Ω Ω Ω Ω O Ω Q Ω Ω Ω Ω Ω Ω O Ω O Ω O gggggggggggggggggggggggggggggggggggggggggggggggggggggggggggg

CD ∞ OO OO OO OO OO OO CD CO OO CO CO rø CXI OO CXJ OO -O CO CO OO CO OO CO -O OO CO C CO0 C∞O CαO3 CCOO C-OO CCOO rø_O CO -0 00 CO CO CO CO -J -J -J -J -J -J -J -J -J l -J -J -J -J -J I -J -J o o o o o ooo oo o o o oo o o o oo o oo o oo oo oo o © _ oO oOO oOO oOO oOO oOO oOO oOO oOO oOOoOO oOO oOO oOO oOO sSSoOD SSOO SSOO SSOO SSOD SSDD SSOO SSOO SSOD SSOO sSOD SSOO SSOO O CO SO SO SO

Js. |ϋ OJ OO OO LO OO OO CO CO LO OO tsJ t CO tO tO tO tO CO CO ^{" "} P P P P P P p PP pP pP pP . ^. oO - oO oO oO oO oO oO oO oO oO sSoO sSoO sSoO sSoO sSoO sSoO sSoO sSoO sSoO sSoD oOoO oCOo oOoO co oo co oo co p o so oo -J cn Ln -!s. J to p o so oo -J cn on rfs. co to p so oo -j cn Lπ rfs. co to p o LLoo oooo --JJ ccnn LL_nn iιfiss.. LLoo ccoo pp oo ssoo __oo --oo c_nrι L_ni iιJjss., LLOθ to p o so c_o -j

Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω a Ω Ω Ω Ω Ω Ω a Ω Ω Ω Ω Ω Ω a O O Ω O Ωa OΩaΩΩΩΩΩ OΩaΩΩΩΩΩa Ωa ffi N H ϋ H ϋ Ω ω .f Ω Ω dd tP Ω Ω td < Ω ω u* α o Ώ ω < to to p μ to p to p to p N H t) Ω H N H CJ Ω dd H β 3 co ' ' ' ^J ' ^y t^H tr¹ tr¹ t¹ tr¹ f tr¹ tr¹ tπ tA tr> IT¹ _H _H tr¹ Ω Ω Ω H CO CO Co CO Co CO CO CO Ki Ki Kj Ki Kj Ki Kj i Kj K. f! t IT¹ P- pa pd a a a a c c co o co o c L cn o co o co c co co a a a

HHH HHHt_ HHHHHHMHHHHHM MHHHH H ___H HHHHH MH HHHH HM HH H HHH H MHHHH HH HH HHH PPPPP PPPPPPPPPP PPPPP PPP PPPPPPPPPP PPPPPPP PPPPPPPP PPP PPPPPPPPP ro oo oo oo oo oo oo co ∞ oo co co αj co ro ∞ co co co ∞ oo co co co ∞ -o co co ∞ co oo ∞ LJi Ln Lπ Lπ Ln Lπ Lπ Lπ Lπ Ln Ln rfs. ι^ ιj rf^ ιt^ rf^ rf__. θJ θ Lθ Lo oo oo Lo to t - to to t p p p p p p p p o o o o o o o o o sD s^

cn cn cn cn _n c^ cn cn cn σι c^ -J -j -J - -J - - -j -j -j -j -_ - -j -J - .j - -j -j -j -j -j -j -j -J co co -^j -J co co - -^j _o so o o p Lo o p to p co p p t L Lo Ln ιi^ Ln cn _π _ ιis. _ i Ln js. Ln cn cn -^

-J i__> ιis. oo _o cn tθ Ln o -θ Lo co Ln Lo w oo LJi ιl-. Lπ Lo Lπ αo on oo ω Ln so -J ι_s. Ln tsj ι)^ t p -J to m c_n θ l|s. OO LO O _^ __S. Lπ rfs. LO CO So O _. LO SO CO ιls. OJ tO CX) P Lo p σ LO Ln Lπ Ln SO C^

Lπ so to .o p σ ω -j ιis, ιjs. - to -j Lθ ω ιo ^ o ∞ σ. ι|s. co !θ p σ^ -J .!s. to -J oo cn ∞ ∞

P t tO tO t CO tJ tNJ -O CO tO IO tsJ P tO P tO CO CO CO IO tO tO LO OO ω co on oπ rfs. W ι|s. Lo ιs^j p o o o o c» o so p Ln cn -- cx) θo oo o o o so so p p M

-J Lo o Lθ θ Lπ tθ ι|s. o o rfs. rfs. cn co Lo so p o c» θJ so p so t Lo αD o -^j Lπ p p so so υι o θ ιIs. C)o Lo co p -J o p on o c^ tsJ Ln -^j Lπ cn o p cxi -^j Ln so Lπ Lπ so co o Lo co cn so to co o ω Lπ LO Ln so cn cn to p Lo co o cn o co p -J -^

Lo -j Lπ so Ln cn oo tθ rfs. ι|s. Ln oo cn -J -J tθ ιls. -j - p tθ ιP- cn Lπ o cn _ts. p cn P P θo tsJ - _n o oπ p o cn to ω w ω cα o LD θ cn p p » uι ω (_) (i> P _ o o cn -j Lo -j _i_oO ωLo _to pp ωoo L__nl μp ιsDo ωLo cn o to

PPPPPPPPPPPPPPPP P P P P P P PPPPPPPPPP PPPPP PPP PPPPPPPPPPP P P P P P ooooooooooooooooooooooooooooooooooooooooooooooooooσooooooσoo oooooooooooooooooooooooooooooooooooooooooooooooooooooooooooo

-J -J -j -o -j - -J cn cn cn -j - -j -j -α -j -j - -j -j -j -j - cn cn -J cn _n cn cn cn -j -J -- -o -J co co oo oo -_ - -. ) -j -j -J o so so o so -o oo oo -J cn cπ Lπ p to to Lo p p p so -J SD P to oo oo -j rfs. oo p to p o on o so o s O Lo -J cn -J -J p o co ifs. i_s. tsJ CO Oo p -j Ln Ln rfs. iis. oo cn p rfs. Lo o co Lo to p _ cn cxi cn cn cn cn cn cn cn cn -j co cn cn cO cn cn -j co σi cΛ cn cn cn -J co cn co cn cn -^

C en en oo oo ro ro o en o en o en o en o en en to to to to to to i ;_-^j to to to ;;y to ;)^y to ;_>

^ >-3 ι-3 >^ β ^ β β !-3 ^μ3 3 t-3 ι-3 !- β β β β >^ β β ^ B ^μ3 β e ι-3 ι-3 β ι-3 ι-3 t-3 β ι-3 ι-3 β t-3 β 3 β β H

Ω Ω Ω O Ω Ω O Ω O Ω Ω Ω Ω O Ω Ω Ω Ω Ω Ω Ω Ω O Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω O Ω O Ω O O O O O Q Ω Ω O Q Ω Ω Ω Ω Ω Ω Ω gggSggggSggggggggggggggggggggggggggggggggggggggggggggggggggg ppppppoooo ooooooooooooooooσσoooooooooo ooo oooooo ooooooooooooooooooooo

O O O S0 S0 l_. s0 S0 S0 L0 L0 S0 U0 C0 C-0 C0 C0 00 Lπ Lπ Lπ Ln Ln Lπ rfs. _|(s. ||s. _|js. _|j___. rfs. rfs.

U P O - 03 -J m uni U -O P o to (D m ui Lπ ιis, Lo co p o so co -J cn Ln ι_s. oo

ΩΩΩH MO DΩΩΩΩddΩa ΩΩOΩΩΩΩΩΩΩΩaOΩΩΩa O Ω Ω O Ω Ω Ω Ω a Ω Ω Ω Ω Ω a tΛ Ω O Ω Ω a CO Ω Ω Ω a Ω ΩΩa

W N H O H α Ω ω ^ ω H a Ω td Ω td l> α Ω dd > Ω td to p CO co p p co p > Ω td

Ω Ω Ω Ω Ω Ω Ω Ω Ω ^ ι-3 β β >-3 >-3 μ3 >-3 β ι-3 >-3 3 .)^{y l} .W Ω Ω Ω Ω Ω Ω Ω ^ ^ ^ ^ ^ ^ Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω C O C C t_o H tH H tH tH tH f -H tH i ; κ; κi κ! κi i ι- κ; i ι _-; _r' tr^, -r< _r^< fr^, _r^l _r' _r^, _r^, lr^, l ^, _r¹ __H ^ ^ ^ w d p ^ cj c c^ ci j p p pd pd d pd ^ ^ ^ ^ ^ ^ α c α cj c! ; c_; α Ω θ θ θ θ _ι co co -j c n co c o ^

H H H H H H H H H H H H H H H H t- H H H M H H H H M H H H H H H H H H H H H H H H H t- H H H M H H H H H H H H H H H H H

P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P

1_O S SO S 0 SO SΩ SO SO SO SO S SO SO O LO SO SO SO SO SO SO SO LO SO SO S VO SO S O SO O SO SO SO OO OO OO ∞ ∞

-j -o -j -o -j -j -J -j - -J -j cn cn cn cn cn cn cn cn -j -j - -j -j -o -j -j -J cn -o -J cn -J -o cn -J c_n _ cn cn cn cn cn cn o^ cn cn c_n cn cn cn cn cn cn cn _n c_n c_n c^ cn o p on cn Ln ii_. Lo co !so p p Ln cn cn -J -J -j -O Lo O P P P OJ CO P O O SO P O SO O O SO o so cΛ -J co Lπ -j Lo on oo -J Lπ Lπ o Lo _ ι(s. oJ rfs. oπ oπ oπ σι cn -J

-J c» co o cn -o _n -O o P to -_i on cn rfs. p LD O O -is. o co on c_n P c» o c» oo rf-. co Ln Lo Ln ip. Ln Lo -j w rfs. ω co c» to co rfs^, so p co σ ιls. o rfs. Lθ ι|s_> oo so !θ θo sD -J o oπ ι(_. to so W Lo -j co w Lπ ιo

-J θ P Lθ Lπ to Lo to o P t>J rfs. Lπ t Lπ σ^ so σ Ln -j -J so co p tso cn αι t>θ cn P cn o cxι co o M -J W ω ω to ω ω to ω tO N^j to to to to w ω to w to M t to to to to M -o ω -O P -O to to to to μ p p μ p μ p p tO -O p p μ H tO H M P H P P P P P P p o o . P θ . o _ „ J vi fc ^ m {n u _- uι m αι uι ι_ι ^ u tj) _^j μ μ ιt) o o μ μ o ι_) co m - si si (iι ιιι μ o ω ι» - (!] θ U) si D j J in (Λ m uι m J oo cn w ife LO Lπ Lo cn Ln σi cn P -J o -J o L.π Lo cn c^ - L -j on -o on rfs. OT rfi tø Ln L co ro to o o Lo rfs. tsJ -J O Ln so so o p so o Lo σi On p -j Ln j-. CD Co i.o rfs. oo cn -o cn co Lxi co -J σ. i-O ∞ c» o c» Lτι Lπ to t cn -j so rfs. p θ ιF^ Lπ rf^ ι|s. L Lo cx_) Lπ o -J c_n o Lo so co tθ Ln Lo tsj p c)o p oo _^ to to tO -o to to to to to to to to to io to to tO -O to to to to to to tO -O to io p μ p p t to to to to to to to to to to to io i to i to to M t to to to to ω u isj to cn cn P Lθ Lθ rfs, ₁p. Lπ Ln -j _n P to to oo L ιts ιt_» Lπ rfs. rfs. to Lθ rfs. oj to oJ C -j -j oo so o p p to to p o to tθ Lo Ln ι|s. ι)s. rfi rf_ on ι -J Ln c_n -J _o -j oo p o so so o ιfs. Lθ Lπ P o -J -O p o -j Ln σι _π ι|s. rfs ι|s. ι|s. ₁p_. so so -J Cβ p so -j -J θo -J oo θ tθ ιfi. αι cn -J to p oo to

Lθ o co co ιts. -j ιJs. -j p t so Lo p tsJ so c_n ι|s. σι on _. -J θo Lo o Lπ so so p -j oo _o Lo o to co ∞

(_xι co L_n _ιs. ι)s. rf__. Lθ Lo t σi Ln c_o t p Lo cχι to t o ιls. p o co -j co p Ln ιf-. p so p so so Lπ

P P P P P P PPPPPPPPPPPPPPPPP P P P P P P P P P P P P P P P P P P P PPPP PP PPPPP ooooooooooooooo ooo ooooooo ooo oo ooo ooo oo oooo oooooooooooooooooo ooo oo oooooooooooooooooo oooo o ooooooooooooo ooooooo ooooo ooooooo cn cn -J -o -J o. σι cn cn cn cn cn cn cn _n cn cn cn _n cn _n _n cn cn cn cn -J -J co c_α oo co -^ il-. OJ Oo p to i.o cn ils. on -J oπ cn rfs. its. tO rfs. rfs. co LO Ln its. j^ LJi Lπ -j co p p o p p o cn rfs. σi s^ o o _fs. -J to (ji p -J cn p co rfs. - o cι Ln rf-. p oo p co o oo p p -J o oo Ln oo -J p oo LO Ln LO rf__. -j Lo on co rfs. p p -J I__{O C}n LO Ul ι|s. O_O Cn θo p oo tO M Ln L_O P

OO O OO O LO O LO O P LO CO Cn P i|s. O OJ O _l|s. p CO OJ θ Lθ oπ Ln oo oπ co tθ Lπ oπ f to rfs. Lπ c_. cn so o P ι_s. c_o uι p P O O Ln o sD Oo co oo on p i o so Ln Ln

P P

∞ cn ∞ oo cn cn cn cn -j ∞ cn ∞ cn cn _n m c_n cn cn cn -J OT OT cn cn -J oo cn ∞

CJ) en en 00 oo ro ro o en o cn o en σ en o cn en to to to to to to to to to to to to < to ;__ ; < to ;_y β β β β β ι-3 β '-3 β ι-3 β β β β i-3 'β ι^ 3 ι^ ι-3 3β 3 β β >-3 β 3 β β β β β β β β β β ι-3 β βι^ β β β β β ι-3 '^ β ι-3 ^ β ^ ^ β ι-3 ^μ3 ι-3 ^μ3 Ω Ω Ω Ω Ω Ω ΩΩ ΩΩ ΩΩO Ω Ω Ω Ω Ω Ω Ω OΩ O Ω O Ω Ω Ω Ω Ω Ω Ω Ω Ω O Ω Ω Ω Ω Ω O O Ω Ω Ω Ω Ω Ω O Ω QΩΩ ΩQ Ω Ω Ω O Ω ggg ggggggggggggggggggggggggg ggggg ggggggg ggg gg ggg Kgggg ggggg Sg oo oo ∞ C-O Oo cxi co co co oo oo oo oo ro oo co cΛ co co oo oo oo co oo oo oo oo co oo oo ∞ oo oo oo oo oo ∞ ∞

P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P c cn c Lπ n Ln Ln Ln Lπ Ln L_π Lπ ιfs. rfs. rfs. ιt__. rfi ιfs. rf_i rf__. rfs. _lι__. o o o Lθ L Lo o Lo ω Lo co p o so co -J cn _n rfs. L C p o so co -j cn L_n vis. L t p o so oo - α-v L_n rfs Lo to p o o co -o cn Lπ rfs. ω

Ω Ω Ω Ω Ω Ω Ω 3 Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω a O Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω O Ω Ω Ω Ω a O Ω to p ooΩ H M α O Ω W O O Ω td α α Ω t D=- Ω dd > Ω Ω td > H H O Ω txf tΩ Ω a Ω Ω

CO P CO P co p t p CO p to p u Ω Ω Ω Ω Ω a α Ώ to > to p

. . . . . . . . ^ >' ' __¹ __¹ t^, t^, t_¹ t t^H |? tD tn ω ω ω to ! < Q θ Ω Q Ω O θ n Ω < < ^ ^ a K K ιo tιι tn tn tn ω tn t» B t. H H l!! B tι| H tιl H H KI I?l t. ^ tr¹ F π tr' F &^y ^ to to to to to -O Co co co to to co

H H M H H H H M a a a a a s cii cj j c ci ci ϊd pd ^ td jd j tH t > f A c. Cl -__i t^{H H} E^H t¹ E^H t^H t' ^lτ) n3 iti nj 'c) ⁱτ_) 'τ)

H H H H H H M H H H H H H H H H H H H H H H H H H H H td H H H H H H H H H H H M H M H H H H H H H H H H H H H H H H H M to co to to to co to co co co to to co tsJ iso co- pi— p i— ip— ip— Ip— ip— p r— ip— ip— p i— p I— ip— Ip— ip— p I— p I— ip— Ip— tp— ip— tp— p i— p I— ■p— ip— tp— ip— ip— i— P P P P P P P P P P P P P P P

Oo Oo O O O O O O O O O O O O O OO SSOO SSOO SSOO LLDD SSOO SSOO SSOO SSOO SSOO SSOO SSOO SSOO SSOO SSOO SSOO SSOO SSOO SSOO SSOO SSOO SSOO SLOO SOO SLOO SLOO SSOO SSOO SSOO O SO LO O SO SO SO SD O SD SO SO SO ^ P P p p p p p P o o o o o o o oo ssoo ssoo ssoo ssoo ssoo ssoo ssoo tøi-o ∞co ∞co ∞co ∞co cooo ∞oo --jj --JJ --JJ --JJ --JJ --JJ --JJ ccnn c_nn ccnn ccnn ccnn ccnn ccnn _r. c^ Lπ Lπ L^

cn cn σi cn -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -J -O -J -J -J -J oo cn so -J rf-> CO .I_. LO LO __O LO tO LO p t_O LO LO OO CO CO OJ CO P P P O P o oo p so oπ oo p co oπ so ^ ιfs. ιi__ o t

Lθ Lo -j L c» Lπ rfs. -o oJ oo μ u t ^ ω ^ ^ ω ^ W M o μ μ μ μ o μ U ι|i t μ p _ o ω (Ji J m θ3 M (i) - o ω co m (n oι to μ w ω u ^ ι^ ijι u m -J (iι uι ^ - i μ ιo o μ - σ. ω rfs. to -J σ-ι to o o o to so cπ ιi--. cn cn cπ o p o ro cn p ∞ L_π w. ιθ Ln ω .t-. cn o ι_s. σ o ∞ (Λ ) (i) iι m ω uι ω u H W J i_ι u o α) M uι m P . - ^ (B o _o o o μ oi Ni αι co -θ m to m o ω α) ω J vi (iι o _- ιo - αι to _o P (o p o _=> tθ -n oo to αo Lθ o cxι o o cn cn Ln cn to -J oo -J θ ιfs -j so p t cn oπ LD θπ ι_3 js. o so ιts - P Ln o cn to -J o ιl^ on

||S, rf__, ,|__> ||S. ι^ ,l__. rf__. ,|_-. ₁|^ J__, rfS, rf--. t|S. rf-_. ||^ rf--. rf--> rf--, ι|--> rf-. |^ oπ cn cπ c. c. Lπ cn c^ ifs. Ln σ. -J cn ils. rfs. LO Lo tsj p p p p p o o o o o so CD -j -j Lo oπ Lπ Lπ Lπ i^

∞ so cn cn o ∞ _n p so co .-α t rf--, ιo .-J ω c_n so cn Lπ Lθ P ι!s. c» o P -θ P Lπ p -j ω ! to p o co tsj rfs, Ln o o co -j so Ln D CD cn ifs. p cn its. Ln oo Lo to o Ln p - cn to rfs. to co Lo _j co so on p p so _n oo c^ so p p p oo ιf-. o o __7i o o Ln ιts ι|s, o _^ o -J i -θ oo σ^ ιfs. oo rf^ oπ p ιj_i to Ln cx) Ln t to oo so w Ln Ln ω

PPP PPPPPPPPPP PPPPPPPPPPPPP PPPPPPPPPPPPPP PPPPPPPPPPPPPP o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o

O O O O O O O 3 0 0 CO C___⁾ O _> O Cl CO C__ι O C_> O O O O C__ι O __) O O _D O C) O C__) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 rf^ rfs. ||__. ιfs. ιi__. ijη Lπ L n αι n cn σι n Ln c cn c_n Lri Ln Lπ Lπ Lπ Ln Lπ Lπ n cπ oπ w ω Ln rfs. -j -j o cθ ιf-> oo cn rfs. ι). ω p _o P rfs. p -j -J oo so so w so ∞ o co ∞ c_o oo cn so -^ oo rfs. s o ιf-. co p p cn ι_3 C _o oo t -θ cn p cn on cn ιfs. tsj -j Lπ Ln oπ oo ^ oπ σ o o Lπ cn so θ L^ cx) Lo oo rf^ -j oo σι co rfs. Ln -j M cn tO p so <_Λ θo oo rf^ Lπ c_o rf^ p - Lo - _n Lπ Ln Lo ι ι_5 ιf^ m m m m m m tn J o3 θi o (» m σι oι θ m oι m σι m σι _n -J c» m co oι σι θ co m cn σι m (Λ J m m ffl ra _Λ

CD en en J oo oo IV) io O cn o en o cn o on σ on cn to to to toto to to to to to to to to to to toto to to to to to to to to to to toto to to toto to ι- 3 ι-3 β H i-3 ι- 3 >-3 β !-3 β ι^ β β ι-3 H β ι-3 β β ι- β β ιβ 3 ι-3 β ι-3 β β ι-3 3 t- β ι-3 ι-3 β

Ω Ω Ω OΩ O Ω Ω Ω ΩΩ Ω Ω Ω Ω Ω ΩΩ O Ω Ω Ω Ω OΩ O Ω Ω Ω Ω OΩ Ω ΩΩ Ω Ω ΩΩ Ω Ω Ω Ω Ω Ω ΩΩ Ω Ω Ω Ω ΩQ O QQΩ O Q gg gggggg ggg g ggggggg ggggggg gg g gg g g ggggg gg gSSgg cx> oo co c» oo oo oo oo co _o oo oo co oo oo oo oo oo oo co _o co oo oo oo cx> cx> oo co o_ _o oo co _o _α co ∞ tO tO tO tO tO t t IO tO tsJ tO tO CO tO tO I tsO M tO I tO W IO CO CO P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P tO t CO -_O CO P P P P P P P P P P O O O O O O _{O O} O S_O LO so LD SO LD o S_O SO o CO OQ OO OO OO CO Oo CO OO CO -J -J -J -J -J -J -J -J -^ i^ Lo co p o Lo oo -J _^ Ln rfs. LO M p o Lo oo - cn on rfs, oo Nj p o io co - cn Ln rfs. Lo co p o so _o -J OT

Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω _^H ^' t^H t tH tH | Ω Ω Ω Ω Ω O Ω Ω Ω Ω Ω Ω O O Ω O Ω Ω OΩa Ω Ω Ω Ω Ω a Ω a Ω Ω Ω Ω Ω ΩΩ Ω Ωa Ω i + i + i + i + i + .il ffi K ffi K K ffi ffi W K E W K .iI ^μS i^ N H a Ω td N H O Ω td > N H O Ω td > pp ttssoo pp ttoo pp ccoo pp ccoo pp ttssJJ ccoo ccoo ccoo tt ttssjj ttoo ttoo ccoo ccoo ttoo bboo ccoo ccoo iioo ccoo pp to p Ω _S _g _S __S ≤ -S ≤ -_g -g _3 _S __ -S ≤ Ω Ω Ω Ω t¹ _^H _^H _^H _^H _^H _^H |_rι t ^l _r^l ___^H _r^< lr^, t^H L^ -H _H to to to to to to to to to to n_ HJ tr ^ tr !j^ __r |j^ l_r^l ! l- - _^ !j !j ! |^y _w !^ ' ^l | ^ Ki Ki fd jd pd pd pd pd jd pd pd pd pd li: iii ρ u p to p t p ι p ι β . . _. . . . _. . β _{. . .} . i κi ι< κ; oι to . [_ [_ t_ _ [Λ to (_ (n [ _o t_ t_ [n _ [n m H H

H M H H H H H H H lH_l -_SS* «_ϊ_' -_S_' «_?S -_Sg' «_-S< '_S_^, ^__^, _«ϊ3' «_S_' «_-3^, ^__' -_S3^, -S¹ l H1 H H H H t. t. M K H H B H M H P- M H H H H H H H t- H H H H H H H H H H M tO tO tO tO tO N tO l M tO M tO tO tO t U tO tO tO tO tO tO tO M M tO tO tO tO tO tO M W tO tO M

P P P P P P o o oo oo oo oo oo oo oo oo αo oo αo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo oo o oo o so oo - cn on its. oo to P rfs. co co p o so co -J cn _n rfs. oo co on Lπ Ln Ln Lπ j_. ιfs. ιi_, |f_. rf_. rf_. rfs. ιf_₁rfs. L Lθθoooo _o _o _o _o to co!sθ NθW P

cn -j cn on co p to p co cn cn _n cn cn oπ oπ co oo to cθ rfs. ιfs. ιf_. ι^ _n cn _n -4 σι cn o. _n _^ rfs. s_₂ its. on - σ-ι θ -J ι cn ιfs. _n o ιfs. Ln Lπ on cn ι|s. -j _o so ^ -θ so so so o so co oo ∞ ^■ •

W ι(_, o θ ιfs -j Lπ _n o rfs. - _n co o -J cxι o o cx) ∞ to sD p -j so Lo -j o so p o Lo --j ! co Lπ o p -J _^ co o to _o p cn o cn so LJi Ln ifs. o -o p _o ifs. rf-. - co p to p o Lo co iis. to Ln p so co rfs. Ln Ln i^ cn o cn co co co co -J to o co p - -J -J co co on tθ (Tι so P Lπ -j -J cn -J Lπ co so p _o ιfs. oo co _π p o L^

-O rf_. cn -j _n cn rfs. co _o P rfs. ιi_, _θ Ln cn Lπ Lπ cn Lθ rf_. co t>o co to Ln oπ oπ on cπ ιi_. Lπ Lπ Lπ Ln Ln Lπ Ln rfs. rfs. rf^ o _n -J cn -J .ts. rfs. co p p p to cn -J Co cn -J θ _n P ιfs. to to c^ ιo oo to o o so o co rf_, oo co p o so -J co _o oo -J - cn -o oπ - _n s^

— o _ -J - o —o c .o . p -J _ . P c _n. o_. oo -j -j _n t ιi_. c» θ L^ _n Lπ so so co cn co rfs. co Lo _-_\ _o to o ιfs. p -j ω ω -j p _n co p _. _n o so p p p s_5 _o c3-ι co co co -_ι o θ- s_) rf , a. rfs. c on c_n con --jj pp c .x.3 i M iis. o c so LJi P Lo _o o to cn co .F-. o ¹ ^ o co ^cn ^σ. ip--» cn 'c"n cn p cn -o Ln cn o so ιi-. Ln co oo cn -J cn co to _o so o ~J θπ θ P θo to -j rfs. - cn co co rfs. rfs. o rfs. - co o oo co Ln P its. so o cn co tO its. -j O -J SO OO -J OO O t o cn co w so p cn p - co oo oj |js, -j p so o p cn co rf-. oo on tθ -o -j ι

P Oo P Co p Oo p OO p OO P P P P P P p p ϋi ui ui ui ϋi ui Ln ^ iti ϋπ ω ui ϋη ui ϋi ϋπ ϋπ ϋi ui ui -i ui ϋi iti ϋi i ϋi ϋi uπ Ln co -j to -j oo oo co co co -J so co -j on sD cn σ. -J 10 U (S m m 01 1 01 lJ 01 ^ ai - O P l0 U M U W ^ Ul ^ l_ IJ I0 P _ O I t0 t0 P P P P O C0 (I! (D

_s. cx) OO L o lNO p on -j so Ln o co cn p i_5 rfs o _n o ifs. co co Ln Ln Ln _o co oo L - ifs cn so t -^ ιts. Lo Lθ o _n o so o Lπ so cx) θo so co oo ι_> p Lo p ι_D θ rf_. p Lo Ln o rfs. ₁ι_. so co ιts. cn _^

O _OT ιfs. p -J S0 O -n ιts. S0 -J tO L0 C0 C0 -J CD ιfs. _0 _n rf-. O L0 LJl P -J rf-. _0 ι|S. S0 -J L0 ω

PPPPPPPPPPPPPPPPPPPP PPP P P P P P P P PP P P P P P P P P P P P P P P P P P P P P

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O σ O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O ιts. _o cn -θ ιfs. _o _n co ι|s, -j oπ Ln Lo o rfs. Lo tθ L Lπ rfs. ιf_. co Lθ (ji Ln Ln on oπ on Lπ _^ co Lπ so P Lπ Ln t o Lo _. _o M P cn p p c» co p p co -j Lo o rfs. Lo ι|s. t Lθ rfs. rf_. co _n Ln rfs. o co Lo ra

O W rfs. P -O LO _0 1_5 -J -J _D W C» SO -J C I CO Lπ -J -0 -J O -J O i0 1_3 Lπ -O O SO O L^

Ln _o -o o -J Co -j c⁾o ρ so Ln ιts. co ι_5 so to so p o rfs. Ln p to ιts. Lo co rfs. _n p to p ιt P ιt^ p co p co p co p co p co -J o -J θ -J o -J o -j o cn co oo oo oo oo oo co oo oo cβ oo cx) CX) CX) _o cn c3i -J CX) cn -J cn cn c^

CD en cn ro O en o cn J oo co ro o en o cn o cn cn

3μ3 3 μ3 ι-3 3 3 β ι^ 3 ι-3 β β ι^ β 3ι^β ι-3ι-3 ββββ ββι-3ββββιβι-3 ^ β ι^ ι^ ι-3μ3 β ββ ι^ β ^ '^ ^ θ ι^ β β μ β ι^ ιβ β . β ΩO Ω Ω O Ω ΩΩ ΩΩ OO Ω ΩO ΩΩΩ Ω Ω Ω Ω Ω O Ω Ω Ω Ω Ω Ω OΩ Ω Ω Ω Ω Ω Ω O Ω Ω Ω O ΩΩ ΩOOΩΩ OΩΩ ΩQ Q Ω Ω Ω O gggggggggggggggggggggggggggggggggggggggggggggggggggggggSgggg

CO CO CO CO _O CO CO CO CX> CO OO OO OO CO CX> CO OO OO OO OO CO OO _O C» OO CO CX. CO CO OO CO co co co t to w to w w to to t w to to to to to ω to to to M to w to M to w to to ω w co co cx. oo OT Co -j -j -j -J -J -J -J -j -J -J cn σι <3^ σ. cn cx. σ. cj. c^ Lπ rfs. Lθ M p o o _o - _n on ιjs. _o co P θ o cx- -j _n oπ ιCs. _o to p o so co -J _n Lπ ιj^

Ω Ω a Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω Ω a O Ω Ω Co a Ω Ω Ω Ω Ω Ω Ω Ω P CO oo Ωco pΩ co rfs.Ωoo -J'ΩcnΩ_nΩrfs.Ω_oΩ_oΩpa_oΩLoΩto pΩ P rfo_. _o -ΩoΩ_n cΩπΩrfs. oΩoΩ_o pΩ Ω Ω Co a _o c co p p p rf-. oo -o σ_. oπ ιts. oo co p co oo M p p p rfs. oo -J σ. oπ rfs. J to

H H H H H H H H H H H C- H H H H H H M H H H H H H M H H H H H H t- H H H H H H H H H H H H H H H H H H H H H H tXl H H H M n_l iτ_ iτJ >τj ι-ti id n3 it) _ n_ τ_ι ι-d π_ι n_ι π3 i_j π ^ ιt. W

_^H _^H |r^l lr¹ _^H |r^l l_^H _^H _^H _^H _^H |r^{i |}→ _^H |rⁱ _^H _^H _^H _^H _^H tr¹ _^H _^H _^H P

U_l rfs. rf_, _lf_, |fs. rf^ rf_, rf_, rf_, ιf_, rfs, |f_. rfs. rf_, rfs, ||_. L L L LO L0 0 0O 0O 0o ω

^ σ _^ o c cn cn c __Λ C. cn _ c. __. cn cn o ιf_. rf_. rf_, rf_. rf_, L L L ιjs. js. oo _ιj^ co cD θo -J cn -J -J co ] co oo oo - -o -j - s_. ι^ oo p co p so cx) So P o so o to ιso oo o co o o o o so oo o tø

C01 S0 O C0 Lπ rfa. p C P Lπ C0 P ιts. _^ C0 S0 C0 t>J S0 C0 P 00 _n P C0 CX. P P O O ιts. O O 00 cn !O P P O O -0

Lo on o p M cπ -J - cx. co to w so rf^ so ιfs. _o o P so L^ o p o o Lπ rf-. so -J so to -j Ln to rfs. rfs. ∞ σι _o co p so _n to so ιC_. cn _n oo ι_. _o _n co ιo co cn so p rfs. o o Lθ ιis. rf_. to co p co co so rf^

-O oπ Ln Lπ Lπ Lπ Lπ Ln t-n Lπ Ln Lπ Lπ Lπ Ln Ln -j -j c. -J cn cn cn cn -j σ. cn '-J -o cn -J ιfs. Lπ Ln rfs. Ln rfs. rf_. rfs, rf_, rf_. rfs. ι|-. |fs, ||s. |t_ p tO tO tsJ tθ CO P P P CO tO P M ιfs. -J C0 tO L0 L0 Ln -J LX) CXι rf-. 0n -J 0^ ιts. rfs. O O 00 O S0 S0 S0 S0 O o S0 O O S0 O -J P O S0 O C0 Cn m _. S C0 __. -J L0 U0 S L0 ifs. C0 00 C0 SO SO S P P S0 O CO

Lo Lo -j o co co o -o o co so so on rf_. o Ln -J Ln -j -J _n to cπ σι co cn on oo Ln o Q. ιts. cn co cχi Ln co Ln αo

-j rfs. Ln o o to to p vj to oo o cn co co so σ. o to ω ω ω M to io ω to to M to to to to to M to to ω w to ω u to ω to to w oo -j p to o P Lπ o o co cn -J cn Ln ιfs. Lo co co co p t cn p o o -o oo -J θπ on -θ oo Cθ Lo p t cn P o ω

Lπ P ιt-. Ln co _o _n _n ι_n lo _n -j p o Lπ p Lθ Lo Ln Lθ Lo p cjι co _n ιls. on p j o so on -j oo cn co _π ∞ p cn C io P so o so to so ιls. o oπ - rfs. o so ιCi Co o so t Ln Lθ Lo o o co oo o o o -J θ so so cn o _n cn ι!s. _π rf^

P so LO SO LO Ln sθ rfs. oO Cn _n P C3 P S S_3 l)s. CO Lπ P O LO t Cn O -O CO ιfs. CX. LO O -J So -J tO

P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P P p p p p p p

O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O o o o o o o o o σ o o o o o o o o o o o o o σ o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o σ o o

P P P P P P P P P P P P P P P P P P P P P P P P P P - P P P P P P P P p P

O SO P P P P O O σ o O O SO O O O LD P P P P O SO SO LD O SO CO o O O SO P P P P O SO SO SO O O So O O O SO P P P P O SO SO SO O SO -D SO O co so p p co t co o o o p o so p on so -J p p to co o Ln - -j o co cn '-j rfs. so cD p p -o to w on cn -J p o -o o rfs. co ∞ cn cn on co -J Ln θ rfs. o o σi L -J C -J W LO !0 1-. CX. ιfs. j ^ L O t c^ -J P θπ Ll LO OO CO W rfs, cn p rfs. P CO CO P p t>J Cθ M O S O C p -J C O Ln tO ιti -J ∞ tO (X> -J ιf oπ LO CO Lπ rfs. LO CO -J _^ p p p p c. -_ -o _o co cn -J oo cn σ. cn cn _. _n _n cn -J oo cx. crι cn -J oo cn cn σ. cn σ. c^ σι ι oo o. σ\ σι c. (J\ -i oι

ATOM 8286 C2 HEP 5 62.164 25..268 24. ,495 1.00104.37 6

ATOM 8287 C3 HEP L 5 64.426 25. .352 25. .555 1. ,00 99.26 6

ATOM 8288 C4 HEP 5 65.270 25. .934 26, .676 1. ,00 98.50 6

ATOM 8289 C5 HEP 5 63.215 26 .126 27 .960 1, .00 99.10 6

ATOM 8290 C6 HEP L 5 62.366 25. .505 26, .903 1. ,00100.20 6

ATOM 8291 . C7 HEP L 5 65.381 26 .089 29 .165 1, .00 98.56 6

ATOM 8292 C8 HEP L 5 65.085 27 .500 29 .708 1. .00 98.97 6

ATOM 8293 04 HEP 5 64.379 27 .406 30, .942 1. ,00 98.36 8

ATOM 8294 Nl HEP L 5 63.001 25 .830 25 .594 1, .00101.58 7

ATOM 8295 SI HEP L 5 61.935 24 .146 21 .985 1. .00112.71 16

ATOM 8296 01 HEP 5 62.912 24 .120 20 .912 1 .00112.36 8

ATOM 8297 02 HEP L 5 60.852 25 .151 22 .006 1, .00111.63 8

ATOM 8298 03 HEP 5 61.166 22 .846 22 .024 1, .00111.95 8

ATOM 8299 N2 HEP L 5 64.610 25 .582 27 .957 1, .00 98.40 7

END

Atom

Type Resά .due # X Y Z OCC B

Table 1 : Structural coordinates of AChBP

"Atom type" refers to the element whoose coordinate are measured. The first letter in the column defines the element.

"Residue" refers to the amino acid in the AChBP protein sequence, using the standard three letter abbreviations known in the art.

"#" refers to the residue number.

"X, Y, Z" crystallographically define the atomic position, in three-dimensional space, of the element measured.

"OCC" is the occupancy volume.

"B" is a thermal factor that measures movement of the atom around its atomic center.

Claims

1. A water-soluble protein derived from a mollusc being capable of binding a ligand of a ligand-gated receptor.

2. The protein of claim 1 , wherein the ligand is acetylcholine, gamma-ami no- butyric acid (GABA), glycine or serotonin.

3. The protein of claim 2, wherein said protein is a acetylcholine-binding protein (AChBP).

4. The protein of any one of claim 1 to 3 which is capable of forming multimers.

5. The protein of any one of claims 1 to 4 which is derived form a Pulmonata species, preferably from a Basommatophora species.

6. The protein of any one of claims 1 to 5 comprising an amino acid sequence selected from the group consisting of:

(a) an amino acid sequence as depicted in any one of SEQ ID Nos. 2, A, 6 or 8 or a functional equivalent thereof, or a fragment of at least 5 continuous amino acids thereof;

(b) an amino acid sequence having at least 30% amino acid identity to the amino acid sequence of any one of SEQ ID Nos. 2, 4, 6 or 8.

7. A water-soluble ligand binding protein capable of binding a ligand of a ligand- gated receptor and comprising at least 5 continuous amino acids of the aminoacid sequence depicted in any one of SEQ ID Nos. 2, 4, 6 or 8 and/or said protein is detectable by a monoclonal or polyclonal antibody which recognises, preferably with a binding affinity of at least 10^"7 , a protein of any one of claims 1 to 6.

8. A water-soluble protein being capable of binding a ligand of a ligand-gated receptor comprising

(a) at least the amino acids of the water-soluble protein of any one of claims 1 to 6 determining solubility of said protein, in the same or corresponding positions as in said protein; and

(b) at least 4 amino acids determining binding to said ligand.

9. The protein of claim 7 or 8 which is capable of forming multimers.

10. The protein of any one of claims 7 to 9 comprising 200-240 amino acids.

11. The protein of any one of claims 7 to 10, wherein the ligand is acetylcholine, nicotine, lophotoxin, d-tubocurarine, carbamylcholine, galanthamine or epibatidine.

12. The protein of any one of claims 1 to 11 , wherein said ligand-gated receptor is derived from an arthropod (preferably insect), a plant (preferably a higher plant, most preferably a seed plant) or a chordate (preferably a mammalian, most preferably human).

13. The protein of any one of claims 7 to 12, wherein said ligand-gated receptor is a nicotinic acetylcholine receptor.

14. The protein of any one of claims 7 to 13, wherein said amino acids determining solubility are in the same positions as in the AChBP having the amino acid sequence as depicted in any one of SEQ ID Nos. 2, 4, 6 or 8; preferably in which said solubility-determining amino acids comprise solvent accessible regions in the crystal structure according to Figure 10.

15. The protein of any one of claims 7 to 14 comprising an amino acid sequence having at least 40% amino acid identity to the amino acid sequence 20-223 of any one of SEQ ID Nos. 2, 4, 6 or 8, in which the ligand binding amino acids have been replaced with the corresponding amino acids of a ligand-gated receptor.

16. The protein of any one of claims 7 to 15, in which said solubility-determining amino acids (a) comprise hydrophilic amino acids (Asp, Glu, Arg, Lys) from the sequences 20-44, 73-81 ,. 86-92, 112-120, 135-152, 166-189, 196-20, 209-213, and/or 219-227 of SEQ ID No. 2.

17. The protein of claim 16, in which said solubility determining amino acids (a) comprise amino acids Asp(36), Asp(68), Glu(115), Arg(137), Asp(143), Asp(148), Glu(150), Arg(167), Arg(189), Glu(215) of SEQ ID No.2, wherein Asp may be exchanged for Glu and vice versa and Lys may be exchanged for Arg and vice versa.

18. The protein of any one of claims 7 to 17 which further comprises the amino acids Cys(142), Thr(149), Ala(163), Thr(154), Cys(155), Arg(156), lle(157) and/or Lys(158) of SEQ ID No. 2.

19. The protein of any one of claims 7 to 17 which comprises the amino acids (b) Pro(39), Trp(77), Trp(101), Pro(103), Asp(194), and/or Ser(161) of SEQ ID No. 2.

20. The protein of any one of claims 7 to 19 in which the amino acid sequences 165-169 and/or 200-203 of SEQ ID No. 2 have been exchanged with the corresponding sequence of the ligand-gated receptor.

21. The protein of any one of claims 7 to 20 which is capable of binding a ligand of an acetylcholine receptor, in which at least one of the amino acid sequences Trp(101) - Tyr(T08), Trp(162) - His(164) and Tyr(204) - Tyr(211 ) of SEQ ID No. 2 have been exchanged with the corresponding sequence of the acetylcholine receptor.

22. A method for the production of a water-soluble ligand-gated receptor or a corresponding ligand-binding domain or for improving the water solubility and accessibility to crystallization of such a receptor or domain, said method compπsing altering the amino acid sequence of the extracellular domain of a iigand-gated receptor by way of substituting, adding, deleting or modifying at least one amino acid at a position corresponding to an amino acid determining or contributing to the water-solubility of the protein of any one of claims 1 to 21.

23. The method of claim 22, wherein the ligand-gated receptor is defined as in any one of claims 1 to 21.

24. The method of claim 22 or 23, wherein at least one amino acid is altered to the corresponding amino acid of the amino acid sequence depicted in any one of SEQ ID Nos. 2, 4, 6 or 8, or to a an equivalent amino acid, preferably in which said solubility-determining amino acids comprise solvent accessible regions in the crystal structure according to Figure 10.

25. The method of any one of claims 22 to 24, wherein loop Cys123-Cys136 of SEQ ID No. 2 is inserted into the corresponding region of the ligand binding domain of the ligand-gated receptor.

26. The method of any one of claims 22 to 25 further comprising

(a) culturing a host cell transfected with and capable of expressing a polynucleotide comprising a nucleotide sequence encoding the altered amino acid sequence; and optionally

(b) recovering said water-soluble ligand-gated receptor or corresponding ligand-binding domain from the culture.

27. A water-soluble ligand-gated receptor or ligand-binding domain obtainable by the method of any one of claims 22 to 26.

28. The protein of any one of claims 1 to 21 or 27 further comprising a spacer sequence allowing coupling with a carrier body.

29. A fusion protein comprising the water-soluble ligand-binding protein of any one of claims 1 to 21 , 27 or 28, or a binding fragment thereof and a fragment of a ligand-gated receptor

30. A dimer or pentamer consisting of at least one monomer comprising a protein of any one of claims 1 to 21 or 27 to 29.

31. A ligand-gated ion channel comprising a protein of any one of claims 1 to 21 or 27 to 29 or the dimer or pentamer of claim 30.

32. One or more polynucleotides encoding the protein of any one of claims 1 to 21 or 27 to 29, the dimer or pentamer of claim 30 or the ligand-gated ion channel of claim 31.

33. The polynucleotide(s) of claim 32 which comprise(s) (a) a nucleotide sequence having at least 15 continuous nucleotides of the nucleotide sequence depicted in any one of SEQ ID Nos. 1 , 3, 5 or 7 or a degenerated sequence thereof; or

34. The polynucleotide(s) of claim 32 or 33 which is(are) operatively linked to heterologous expression control sequences allowing expression inprokaryotic or eukaryotic cells. .

35. One or more vector(s) containing the polynucleotide(s) of any one of claims 32 to 34.

36. A host cell genetically engineered with the polynucleotide(s) of any one claims 32 to 34 or with the vector(s) of claim 35.

37. An antigen comprising an epitope of at least 5 continuous amino acids of the amino acid sequence depicted in any one of SEQ ID Nos. 2, 4, 6 or 8 and/or said epitope is detectable by a monoclonal or polyclonal antibody which recognises, preferably with a binding affinity of at least 10^"7M, a protein of any one of claims 1 to 6.

38. An antibody specifically recognizing the protein of any one of claims 1 to 21 or 27 to 29, the dimer or pentamer of claim 30, the ligand-gated ion channel of claim 31 or the antigen of claim 37.

39. An oligonucleotide probe comprising a nucleotide sequence having at least 15 continuous nucleotides of a polynucleotide of any one claims 32 to 34 or encoding the antigen of claim 37.

40. A composition comprising the protein of any one of claims 1 to 21 or 27 to 29, the dimer or pentamer of claim 30, the ligand-gated ion channel of claim 31, the polynucleotide(s) of any one claims 32 to 34, the vector(s) of claim 35, the host cell of claim 36, the antigen of claim 37, the antibody of claim 38, or an oligonucleotide probe of claim 39; and optionally suitable means for detection or performing a ligand-receptor binding assay.

41. A method for identifying an agonist/activator or antagonist/inhibitor of a ligand- gated receptor comprising the steps of:

(a) contacting the water-soluble ligand-binding protein of any one of claims 1 to 21 or 27 to 29, the dimer or pentamer of claim 30, the ligand-gated ion channel of claim 31 or a cell expressing said protein in the presence of components capable of providing a detectable signal in response to ligand binding with a compound to be screened under conditions that permit binding of said compound to the ligand-binding protein; and (b) detecting the presence or absence of a signal generated from the binding activity of the ligand-binding protein, wherein the presence/increase and absence/decrease of the signal is indicative for an agonist/activator and antagonist/inhibitor, respectively, of a ligand- gated receptor.

42. A crystal of a protein of any one of claims 1 to 21 or 27 to 29, the dimer or pentamer of claim 30 or the ligand-gated ion channel of claim 31.

43. A crystal of a protein-ligand complex comprising a protein of any one of claims 1 to 21 or 27 to 29, the dimer or pentamer of claim 30 or the ligand- gated ion channel of claim 31 ; and a ligand.

44. The crystal of claim 43, wherein the ligand comprises an N-alkylated hydroxyalkyl and/or a quaternary ammonium ion.

45. The crystal of claim 43, wherein the ligand comprises 4-(2-Hydroxyethyl)-1- piperazineethanesulfonic acid (HEPES), B-bippinatin, lophotoxin, d- tubocurarine, carbamylcholine, galanthamine, epibatidine or alpha- bungarotoxin.

46. The crystal of any one of claims 42 to 45, wherein the crystal effectively diffracts X-rays for the determination of the atomic coordinates of the protein or protein-ligand complex to a resolution of greater than 5.0, preferably greater than 4.0 Angstroms.

47. The crystal of any one claims 42 to 46, wherein the protein has an amino acid sequence of amino acids 20 to 223 of SEQ ID No. 2, or an amino acid sequence that differs from amino acid 20 to 223 of SEQ ID No. 2 by only having conservative substitutions.

48. The crystal of claim 47, wherein the ligand is HEPES.

49. The crystal of claim 46 having (1) a space group of F2-|2i2₁ and a unit cell of dimensions of a=120.6A, b=137.θA and c=161.5A; (2) a space group of PA₂2 2 and a unit cell of dimensions of a=b=141.6A and c=120.δA or (3) a space group of P≥_Λ and a unit cell of dimensions of a=121.lA, b=162.lA, c=139.4A, 13=90.1 °.

50. The crystal of any one of claims 42 to 49, wherein the protein has secondary structural elements that include .alpha.-helix and antiparallel .beta.-sheets as shown in Figure 7, 10, 11 and/or 12.

51. The crystal of any one claims 42 to 50 having a three-dimensional structure as defined by atomic coordinates shown in Table 1.

52. The crystal of any one of claims 42 to 51 having a binding cavity as shown in Figure 6, 8, 9 and/or 13.

53. A method of using the crystal of any one of claims 42 to 52 in a drug screening assay comprising:

(a) selecting a potential ligand by performing structure assisted drug design with the three-dimensional structure determined for the crystal, wherein said selecting is performed in conjunction with computer modeling; optionally

54. The method of claim 53, wherein the ligand-gated receptor is a nicotinic acetylcholine receptor.

55. The method of claim 53 or 54 further comprising: (d) forming a supplemental crystal of a protein-ligand complex by co- crystallization or soaking the crystal of the water-soluble ligand-binding protein of any one of claims 1 to 21 or 27 to 29, the dimer or pentamer of claim 30 or the ligand-gated ion channel of claim 3 , with a potential drug, wherein the crystal effectively diffracts X-rays for the determination of the atomic coordinates of the protein-ligand complex to a resolution of greater than 5.0, preferably greater than 4.0 Angstroms, more preferably greater than 3;

(e) determining the three-dimensional structure of the supplemental crystal;

(f) selecting a candidate drug by performing a structure assisted drug design with the three-dimensional structure determined for the supplemental crystal, wherein said selecting is performed in conjunction with computer modeling; optionally (g) contacting the candidate drug with a cell that expresses the ligand- gated receptor; and (h) detecting a cell response; wherein a candidate drug is identified as a drug when the cell response is altered compared to a cell that has not been contacted with the candidate compound.

56. The method of any one of claims 53 to 55 further comprising an initial step that precedes step (a) wherein said initial step consists of determining the three-dimensional structure of a crystal comprising a protein-ligand complex formed between the water-soluble ligand-binding protein of any one of claims 1 to 21 or 27 to 29, the dimer or pentamer of claim 30 or the ligand-gated ion channel of claim 31 , and the ligand of the ligand-gated receptor, wherein the crystal effectively diffracts X-rays for the determination of the atomic coordinates of the protein-ligand complex to a resolution of greater than 5.0, preferably greater than 4.0 Angstroms.

57. A method of growing a crystal of a protein-ligand complex comprising: (a) contacting the water-soluble ligand-binding protein of any one of claims 1 to 21 or 27 to 29, the dimer or pentamer of claim 30 or the ligand-gated ion channel of claim 31 with a ligand of a ligand- gated receptor, wherein the water-soluble ligand-binding protein forms a protein-ligand complex with the ligand; and (b) growing the crystal of the protein-ligand complex; wherein the crystal effectively diffracts X-rays for the determination of the atomic coordinates of the protein-ligand complex to a resolution of greater than 5.0, preferably greater than 4.0 Angstroms.

58. A drug screening assay comprising soaking the crystal of any one of claims 42 to 52 in a solution of compounds to be screened and detecting the binding of the compound to the ligand-binding protein.

59. The method of claim 57 or 58, wherein said ligand comprises an alkylated nitrogen and/or quaternary ammonium ion.

60. A method of increasing or decreasing the affinity of a drug to a ligand-gated receptor, comprising (a) performing structure assisted drug design with the three-dimensional structure determined for the crystal of any one of claims 42 to 52, wherein said drug design is performed in conjunction with computer modeling; and

(b) modifying said drug to alter or eliminate a portion thereof suspected of interacting with a binding site of the binding cavity or with a non-specific binding site of the protein in the crystal.

61. The method of claim 60, wherein step (a) further comprises the steps of a method of any one of claims 53 to 59.

62. The method of claim 60 or 61 , further comprising after step (b), the additional step of :

(c) repeating the method used to perform structure assisted drug design according to step (a) using the modified drug according to step (b).

63. A method of drug design comprising the step of using the structural coordinates of a water-soluble ligand-binding protein crystal comprising the coordinates of Table 1 , to computationally evaluate a chemical entity for associating with the ligand-binding site or a non-specific binding site of a ligand-binding protein.

64. The method of any one of claims 53 to 63, wherein the identified drug prevents or promotes correct assembly of a ligand-gated ion channel.

65. The method of any one of claims 53 to 63, wherein the identified drug binds to a non-specific binding site of a ligand-gated ion channel.

66. The method of any one of claims 53 to 65 further comprising synthesizing the drug in a therapeutically effective amount.

67. A drug produced by the method of claim 66 or a pro-drug thereof.

68. The drug of claim 67 which interacts with a ligand-gated receptor comprising a pentamer of claim 30 with monomers A to E, wherein the drug binds to one or more primary contact regions of a monomer (residues from A contacting B) defined by amino acid residues 15 to 21 , 44 to 47, 85 to 87, 91 to 94, 122 to

124, 143 to 146, 149, 185 to 187 of the mature protein of SEQ ID No. 2 and/or to one or more of the complementary contact regions of the other monomer (from B contacting A, (identical to residues on A contacting E) defined by amino acid residues 3 to 4, 7 to 8, 11 , 37 to 39, 53, 75 to 77, 96 to 104, 114 to 118 and 163-170 of the mature protein of SEQ ID No. 2; or to the contact regions as identified in Figure 14; or to the corresponding contact regions of the monomers of a ligand-gated ion channel.

69. The drug of claim 68, wherein the ligand-gated ion channel is the nicotinic acetylcholine receptor and the order of the monomers is αγαβδ.

70. A computer readable medium comprising a nucleotide sequence of the polynucleotide(s) of any one of claims 32 to 34, an amino acid sequence of a protein of any one of claims 1 to 21 or 27 to 29, the dimer or pentamer of claim 30 or the ligand-gated ion channel of claim 31 , or the structural coordinates of a crystal of any one of claims 40 to 50.

71. A device comprising the computer readable medium of claim 70.

72. Use of the computer readable medium of claim 70 or the device of claim 71 for modeling an antagonist/inhibitor or agonist/activator of a ligand-gated receptor.

73. Use of the crystal of any one of claims 42 to 52 or its structural coordinates as a template for modeling the 3D structure of a ligand-gated ion channel.

74. Use of the polynucleotide(s) of any one of claims 32 to 34, the protein of any one of claims 1 to 21 or 27 to 29, the dimer or pentamer of claim 30, the ligand-gated ion channel of claim 31 , the vector(s) of claim 35, the host cell of claim 36, the antigen of claim 37, the antibody of claim 38, an oligonucleotide probe of claim 39, the crystal of any one of claims 42 to 52 or a method of any one of claims 53 to 66 for screening or profiling putative ligands of ligand- gated receptors.

75. Use of an antagonist/inhibitor or agonist/activator identified according to a method of any one of claims 53 to 66 for the preparation of a pharmaceutical composition for the treatment of a ligand-gated ion channel mediated or related disorder.

76. The use of claim 75, wherein the antagonist/inhibitor is or is derived from the protein of any one of claims 1 to 21 or 27 to 29, an antigen of claim 37, an antibody of claim 38 or from a toxin of the ligand-gated ion channel.

77. The use of claim 75, wherein the agonist/activator is or is derived from a the protein of any one of claims 1 to 21 or 27 to 29, an antigen of claim 37, an antibody of claim 38 or from epibatidine, acetylcholine, choline, nicotine, carbachol, serotonin or GABA.

78. The use of any one claims 75 to 77, wherein the ligand-gated ion channel is the nicotinic acetylcholine receptor and said mediated or related disorder is Tourette's syndrome, Alzheimer's disease, addiction to nicotine or schizophrenia.

79. Use of ligand of a ligand-gated receptor for identifying and isolating a water- soluble ligand-binding protein from a mollusc.

80. The use of claim 79, wherein said ligand is α-bungarotoxin.