WO2015017652A1 - Sting crystals and modulators - Google Patents

Abstract

The present invention provides STING crystals. The present invention also provides STING modulators that interact with sites present in and/or defined by such crystals. The present invention also provides methods of making and using such crystals and modulators. Other aspects and/or features of the present invention will be apparent to those skilled in the art, reading the present specification.

Description

STING CRYSTALS AND MODULATORS

Cross Reference to Related Applications

[0001] The present invention claims priority to United States provisional patent application no. 61/860,818, filed July 31, 2013, the entire contents of which is hereby incorporated by reference herein.

Background

[0002] The protein TMEM173/STING (stimulator of interferon genes) (Ishikawa and

Barber, 2008; Zhong et al. 2008; Sun et al. 2009; Burdette et al. 2011) is a central player in the innate immune response to nucleic acids, particularly cytosolic dsDNA (reviewed in Burdette and Vance, 2013). STING responds to various pathogens, as well as to mitochondrial damage, and its overactivation may contribute or possibly even trigger the onset of autoimmune disorders such as systemic lupus erythematosus. Drug discovery requires a mechanistic understanding of the cytosolic DNA-sensing pathway. Such discovery is desperately needed for development of agonists and antagonists of innate immunity, and will have a profound impact on anti-cancer and vaccine development, as well as therapies for autoimmune disorders.

Summary

[0003] The present disclosure provides insights into STING structure and function; such insights define agents useful as modulators of human STING, and provide methods and compositions related thereto.

[0004] Among other things, the present invention identifies the source of one or more probems with prior efforts to modulate (agonist or antagonist) human STING, and provides solutions to such problems. The present invention also identifies the source of one or more problems with prior efforts to define or determine hSTING structure, or relevant aspects of hSTING-interacting agents, based on comparisons with STING orthologs. The present invention provides solutions to such problems. Thus, among other things, the present invention provides STING polypeptides, STING crystal (and/or crystallizable) compositions, STING binding agents, systems that tangibly embody or otherwise contrain or utilize information about such polypeptides, compositions, and/or binding agents, and methods of generating and/or using each of these.

[0005] The present invention provides, among other things, a STING modulator whose structure is an analog of c[G(2',5')pA(3',5')p], 5,6-dimethylxanthenone-4-acetic acid (DMXAA), or 10-carboxymethyl-9-acridine (CMA), and includes a moiety that interacts with a residue corresponding to Serl62 and/or Ilel65 of hSTING. In some embodiments, a STING modulator whose structure is an analog of c[G(2',5')pA(3',5')p], 5,6-dimethylxanthenone-4-acetic acid (DMXAA), or 10-carboxymethyl-9-acridine (CMA), includes a moiety that interacts with a residue corresponding Gly230, Gln266, Serl62, or Ilel65 of hSTING, or a combination thereof. In some embodiments, a provided STING modulator includes a moiety that interacts with a residue corresponding to Gln266 of hSTING. In some embodiments, a provided STING modulator includes a moiety that interacts with a residue corresponding to Gly230 of hSTING. In some embodiments, a provided STING modulator includes a moiety that interacts with a residue corresponding to Serl62 of hSTING.

[0006] In some embodiments, provided STING modulators, upon binding hSTING, an antiparallel β-pleated sheet forms over the binding pocket indicative of formation of a closed STING conformation.

[0007] In some embodiments, a STING modulator comprises one or more of the following features: i. ) direct hydrogen bonds to the side chain of Thr267 of hSTING; ii. ) direct hydrogen bonds to the side chain of Arg238 of hSTING; and iii. ) direct hydrogen bonds to the side chain of Thr263 of hSTING.

[0008] In some embodiments, a STING modulator comprises one or more of the following features: i) direct hydrogen bonds to the side chain of Arg238 of hSTING; and ii) water-mediated hydrogen bonds to Tyr240 of hSTING. [0009] In some embodients, a STING modulator comprises one or more of the following features: i) hydrophobic interactions with a residue corresponding to Leu 170 of hSTING; ii) hydrophobic interactions with a residue corresponding to Ile235 of hSTING; and iii) hydrophobic interactions with a residue corresponding to He 165 of hSTING.

[0010] In certain embodiments, the one or more features of provided STING modulators include at least one feature selected from the group consisting of: spatial separation between the moiety and the potential interaction site; energy of the potential moiety-interaction site interaction, and/or combinations thereof.

[0011] In some embodiments, provided STING agents modulate hSTING.

[0012] In some embodiments, provided STING agents are specific to hSTING as compared with mSTING.

[0013] In some embodiments, the present invention provides methods of designing or characterizing a STING modulator comprising providing an image of a STING crystal that includes at least one potential interaction site; docking in the image at least one moiety that is a potential STING modulator structural element; and assessing one or more features of a potential moiety-interaction site interaction.

[0014] In some embodiments, the at least one potential interaction site includes a site of hSTING selected from the group consisting of Serl62, Ilel65, R238, T263, T267, and combinations thereof. In some embodiments, the at least one potential interaction site includes a site of hSTING selected from the group consisting of Serl62, Ilel65, Arg238, Thr263, Thr267, and combinations thereof. In some embodiments, the at least one potential interaction site includes a site of hSTING selected from the group consisting of Gly230, Gln266, Tyr240, Leul70, Ile235, and combinations thereof.

[0015] In some embodiments, the at least one potential interaction site is Serl62 of hSTING. [0016] In some embodiments, the at least one potential interaction site is He 165 of hSTING.

[0017] In some embodiments, the at least one potential interaction site is Gly230 of hSTING.

[0018] In some embodiments, provided methods further comprise a step of providing an image of a potential STING modulator comprising the moiety docked with the image of the STING crystal.

[0019] In some embodiments, provided methods further comprise further comprising a step of comparing the image with that of a STING crystal including a bound known modulator.

[0020] In some embodiments, the present invention provides a system comprising a computer or computer readable medium in which a STING crystal structure, or coordinates thereof, is embedded and/or displayed.

[0021] One feature of the present invention is that it permits assessment of potential and/or actual STING modulators based on both structural and functional attributes. For example, in some embodiments, the present invention provides methods of designing and/or characterizing a STING modulator, which methods comprise steps of (i) using a system comprising a computer or computer readable medium in which a STING crystal structure, or coordinates thereof, is embedded and/or displayed to assess one or more structural features of the STING modulator; and (ii) performing one or more in vitro, in vivo or cell-based assays to characterize the STING modulator. In some embodiments, the one or more structure features of the STING modulator comprise a moiety that interacts with a residue corresponding to Serl62 and/or Ilel65 of hSTING. In some embodiments, the one or more structure features of the STING modulator comprise a moiety that interacts with a residue corresponding to Gly230 of hSTING. In some embodiments, the one or more structure features of the STING modulator comprise a moiety that interacts with a residue corresponding to Arg238, Thr263, Thr267, Gln266, Tyr240, Leul70, Ile235 of hSTING, or a combination thereof.

[0022] In some embodiments, the present invention provides a method of designing and/or characterizing a STING modulator, which method comprises steps of (i) determining the STING modulator binds in the binding pocket having a three-dimensional structure characterized by the structure coordinates of any one of Tables 1, 2, 3, 4, 5, 6, 7, 8, and/or 9; and (ii) assessing one or more structure features of the STING modulator. In some embodiments, the method further comprises the step of defining the three-dimensional shape of the modulator. In some embodiments, the three-dimensional shape of the modulator includes a moiety that interacts with a residue corresponding to Serl62 and/or He 165 of hSTING. In certain embodiments, the three- dimensional shape of the modulator includes a moiety that interacts with a residue corresponding to Gly230 of hSTING. In some embodiments, the three-dimensional shape of the modulator includes a moiety that interacts with a residue corresponding to Arg238, Thr263, Thr267, Gln266, Tyr240, Leul70, Ile235 of hSTING, or a combination thereof.

[0023] In some embodiments, the present invention provides a modulator of STING characterized in that it binds in the binding pocket having a three-dimensional structure characterized by the structure coordinates of any one of Tables 1, 2, 3, 4, 5, 6, 7, 8, and/or 9.

[0024] In some embodiments, the present invention provides a designed STING modulator, comprising the crystallography coordinates of any one of Tables 1, 2, 3, 4, 5, 6, 7, 8, and/or 9, wherein the crystallography coordinates are within about a root mean square deviation of not more than about 1.5 A from the backbone atoms of the amino acids according to Tables 1, 2, 3, 4, 5, 6, 7, 8, and/or 9.

[0025] In some embodiments, the present invention provides a computer system containing a set of information to perform a design or characterization of a STING modulator having a user interface comprising a display unit, the set of information comprising: (i) logic for inputting an information regarding a binding of a STING protein to a moiety known to bind STING protein; (ii) logic for designing a candidate STING modulator based on the binding of the STING protein to the moiety known to bind STING protein; (iii) logic for determing an information regarding a binding of the STING protein to the candidate STING modulator; and logic for making a conclusion regarding a STING agonist or antagonist properties of the candidate STING modulator based on the determination of step (iii).

[0026] In some embodiments, the present invention provides a computer-readable storage medium containing a set of information for a general purpose computer having a user interface comprising, a display unit, the set of information comprising: (i) logic for inputting an information regarding a binding of a STING protein to a chemical known to binding STING protein; (ii) logic for design a candidate STING modulator based on the binding of the STING protein to the chemical known to bind STING protein; (iii) logic for determining an information regarding a binding of the STING protein to the candidate STING modulator; and (iv) logic for making a conclusion regarding a STING agonist or antagonist properties of the candidate STING modulator based on the determination step of step (iii).

[0027] In some embodiments, the present invention provides an electronic signal or carrier wave that is propagated over the internet between computers comprising a set of information for a general purpose computer having a user interface comprising a display unit, the set of information comprising a computer-readable storage medium containing a set of information for a general purpose computer having a user interface comprising a display unit, the set of information comprising: (i) logic for inputting an information regarding a binding of a STING protein to an agent known to bind STING protein; (ii) logic for designing a candidate STING modulator based on the binding of the STING protein to the agent known to bind STING protein; (iii) logic for determining an information regarding a binding of the STING protein to the candidate STING modulator; and (iv) logic for making a conclusion regarding a STING agonist or antagonist properties of the candidate STING modulator based on the determination of step (iii).

[0028] In some embodiments, the present invention provides a crystalline or

crystallizable composition comprising or consisting of a STING polypeptide. In some embodiments, the present invention provides methods of making and using such crystalline or crystallizable compositions.

Brief Description of the Drawings

[0029] The Figures described below, that together make up the Drawings, are for illustration purposes only, not for limitation. [0030] Figure 1 depicts an exemplary crystal structure of c[G(2',5')pA(3',5')p] bound to hSTING^H232 and exemplary details of intermolecular contacts in the complex. FIG. 1A depicts an exemplary 2.25 A crystal structure of cyclic [G(2',5')pA(3',5')p] bound to hSTING^H232 (aa 155-341). The symmetrical hSTING^H232 dimer is shown in a ribbon representation, with individual monomers colored in magenta and yellow, a-helices are labeled from a 1 to a 5. The c[G(2',5')pA(3',5')p] in a space-filling representation is bound in the central cavity at the interface between the two monomers. FIG. IB depicts an exemplary expanded view of the c[G(2',5')pA(3',5')p] binding pocket in the complex. The position of H232 (in green) in a stick representation is labeled in this panel. FIG. 1C depicts an exemplary surface representation of the structure of the complex shown in panel A. FIG. ID depicts an exemplary view in panel C rotated through 90°. FIG. IE, FIG. IF and FIG. 1G depict exemplary intermolecular contacts in the complex of c[G(2',5')pA(3',5')p] bound to hSTING^H232. The bound c[G(2',5')pA(3',5')p] is shown in biscuit color, with individual STING subunits in the symmetrical dimer shown in magenta and yellow. The bracketing of the purine rings of c[G(2',5')pA(3',5')p] by Y 167 is shown in panel E, and intermolecular contacts to the base edges and backbone phosphates of the ligand by the subunits of STING are shown in panels F and G, respectively.

[0031] Figure 2 depicts an exemplary comparison of hSTING^H232 complexes bound to c[G(2',5')pA(3',5')p] and c[di-GMP]. FIG. 2A depicts exemplary Details related to alignment and hydrogen-bonding patterns within the four-stranded anti-parallel β-sheet that forms a cap over the binding pocket on formation of the c[G(2',5')pA(3',5')p]-hSTING^H232 complex. FIG. 2B depicts an exemplary superposition of the c[G(2',5')pA(3',5')p] bound structure of hSTING^H232 (aa 155-341) with both subunits in green and c-[d-GMP] bound structure of hSTING^H232 (aa 139-379) with both subunits in beige (PDB: 4EF4). FIG. 2C depicts an exemplary superposition of the c[G(2',5')pA(3',5')p] in green and c[di-GMP] in orange (PDB: 4EF4) in their complexes with hSTING^H232. FIG. 2D depicts an exemplary expanded view in stereo of the top right segment of panel B following superposition of the c[G(2',5')pA(3',5')p] bound structure of hSTING^H232 (both subunits in green) and c[di-GMP] bound structure of hSTING^H232 (both subunits in orange) (PDB: 4EF4). [0032] Figure 3 depicts an exemplary crystal structure of c[G(2',5')pA(3',5')p] bound to mSting^R231 and an exemplary comparison of its complex with the same ligand bound to hSTING^H23. FIG. 3A depicts an exemplary 1.77 A crystal structure of c[G(2',5')pA(3',5')p] bound to mSting^R231 (aa 154-340). FIG. 3B depicts exemplary intermolecular contacts to the cyclic dinucleotide ring system of the ligand by the subunits of mSting^R231. FIG. 3C depicts an exemplary superposition of the c[G(2',5')pA(3',5')p] bound structures of hSTING^H232 (both subunits in green) and mSTING^R231 (both subunits in magenta). FIG. 3D depicts an exemplary superposition of the c[G(2',5')pA(3',5')p] in its complexes with hSTING^H232 in green and mSTING^R231 in magenta. FIG. 3E depicts an exemplary 1.9 A crystal structure of

c[G(2',5')pA(2',5')p] bound to hSTING^H232 (aa 155-341). FIG. 3F depicts an exemplary 2.1 A crystal structure of c[G(3',5')pA(3',5')p] bound to mSting^R231 (aa 154-340).

[0033] Figure 4 depicts exemplary ITC data on binding of cGAMP linkage isomers to hSTING^H232 and hSTING^H232 mutants, as well as to hSTING^R232, hSTING^A230/R232, mSting^R231 and mSting^A231. FIG. 4 A and FIG. 4B depicts exemplary ITC binding curves for complex formation between cGAMP linkage isomers bound to hSTING^H232 (aa 140-379) (panel A) and binding of c[G(2',5')pA(3',5')p] to mutants of hSTING^H232 (panel B). FIG. 4C depicts exemplary ITC binding curves for complex formation between cGAMP linkage isomers bound to hSTING^R232 (aa 140-379). FIG. 4D depicts exemplary ITC binding curves for complex formation between cGAMP linkage isomers bound to hSTING^A230/R232 (aa 140-379). FIG. 4E depicts exemplary ITC binding curves for complex formation between cGAMP linkage isomers bound to mSting^R231 (aa 139-378). FIG. 4F depicts exemplary ITC binding curves for complex formation between cGAMP linkage isomers bound to mSting^A231 (aa 139-378).

[0034] Figure 5 depicts an exemplary crystal structure of DMXAA ligand bound to mSting^R231. FIG. 5 A depicts exemplary chemical formulas of dimethylxanthenone-4-acetic acid (DMXAA). FIG. 5B depicts an exemplary 2.4 A crystal structure of two molecules of DMXAA bound to mSting^R231 (aa 154-340). FIG. 5C depicts exemplary intermolecular contacts in the complex of DMXAA bound to mSting^R231. The two bound DMXAA molecules are shown in biscuit color, with individual mSting subunits in the symmetrical dimer shown in magenta and yellow. The intermolecular contacts to the polar and nonpolar edges of the DMXAA by the mSting subunits are shown in two alternate views. FIG. 5D depicts an exemplary superposition of the 2.4 A DMXAA bound structure of mSting^{R231 (}both subunits in biscuit) and of the 1.77 A structure of c[G(2',5')pA(3',5')p] of mSting^R231 (both subunits in magenta). For dose dependence: Data points were determined in triplicate and are depicted as means ± SEM.

[0035] Figure 6 depicts exemplary results of cGAMP stimulation of the IFN pathway in mouse and human cells. FIG. 6A depicts an exemplary result showing BMDMs (1 x 10⁶) from C57B/6 mice were treated with increasing concentrations (5, 10 and 20 μΜ) of cGAMP linkage isomers, c[G(2',5')pA(2',5')p], c[G(2',5')pA(3',5')p] and c[G(3',5')pA(3',5')p], and cells were collected at 4 h post-treatment. cGAMP linkage isomers were provided by addition into media. Mock treatment control was included. qPCR analyses of Ifnbl, 116 and Ccl5 mRNAs were performed. FIG. 6B depicts an exemplary result showing BMDMs from IRF3 ^{~ ~} and age-matched wild-type control mice were generated. Cells (1 x 10⁶) were treated with cGAMP linkage isomers, c[G(2',5')pA(2',5')p], c[G(2',5')pA(3',5')p] and c[G(3',5')pA(3',5')p] at a final concentration of 15 μΜ. cGAMP linkage isomers were provided by addition into media. qPCR analysis of Ifnbl, 116 and Ccl5 mRNAs were performed. FIG. 6C depicts an exemplary result illustrating murine BMDMs were incubated in media supplemented with indicated

concentrations of cGAMP isomers for 18 h (left panel), or for 30 min with and without

Digitonin-mediated permeabilization (right panel). 18 h later, IFN-a concentrations in the supernatant were determined by ELISA. FIG. 6D depicts an exemplary result showing THP1 cells were incubated in media supplemented with indicated concentrations of cGAMP linkage isomers for 18 h (left panel), or for 30 min with and without Digitonin-mediated

permeabilization (right panel). CXCL10 concentrations were determined by ELISA after 18 h. FIG. 6E depicts an exemplary time-course of STING-dependent IFN pathway activation by cGAMP linkage isomers. THP1 cells were incubated in media supplemented with cGAMP linkage isomers from 0 to 12 h without permeabilization. IFNB1 and CXCL10 transcriptional activation was measured by RT-PCR, normalized against TUBAIB and vehicle control. For bar graphs: Data points were determined in triplicate and are depicted as means ± SEM.

[0036] Figure 7 depicts an exemplary mouse and human STING mutational analysis.

FIG. 7A depicts an exemplary experiment where HEK293T cells were transfected with reporter constructs and human or murine STING expression plasmids as indicated. After 12 h, cells were digitonin permeabilized to deliver cGAMP linkage isomers (5 μΜ concentration, 30 min permeabilization) and incubated for an additional 12 h, followed by luciferase-reporter assay. FIG. 7B depicts an exemplary experiment where, to gauge STING mutant stimulation by murine cGAS compared to the inactive cGAS mutant E211A, plasmids containing the indicated human or murine STING variants were cotransfected with either cGAS form and luciferase reporter constructs. Luciferase induction was determined after 30 h. In this setting, the transfected plasmids provide the dsDNA stimulus for cGAS activation. Activation is expressed as fold induction in relation to control plasmid pMAX-GFP. FIG. 7C depicts exemplary results where HEK293T cells were transfected as in panel A and stimulated with cyclic di-GMP (5 and 10 μΜ) following digitonin permeabilization. Luciferase activity was determined 12 h after stimulation. As negative and positive controls, HEK293T cells transfected with hSTING^H232 were mock- treated (white bar) or stimulated with 5 μΜ c[G(2',5')pA(3',5')p] following digitonin

permeabilization (green bar), respectively. FIG. 7D depicts an exemplary experiment where HEK293T cells were transfected as in panel C and after 12 h stimulated with medium containing DMXAA (136 and 266 μΜ). Luciferase activity was measured after additional 12 h. FIG. 7E depicts exemplary ITC binding curves for complex formation between DMAXX and mSting^R231. FIG. 7F depicts exemplary ITC binding curves for complex formation between DMAXX and hSTING^R232/A162 andhSTING^R232/V162. FIG. 7G depicts exemplary ITC binding curves for complex formation between DMAXX and hSTING^H232/A162 andhSTING^H232/V162. FIG. 7H depicts

[0037] Figure 8 depicts exemplary surface views of the crystral structure of c[di-GMP] bound to hSTING^H232 and exemplary details of intermolecular contacts in the complex. FIG. 8A depicts an exemplary 2.15 A crystal structure of c[di-GMP] bound to hSTING^H232 (aa 139-379) (PDB: 4EF4). The representations and color codes are the same as used in Figure 1A. Note that the two loops that protrude over the binding pocket are disordered for about half their lengths as one proceeds towards the tips of these loops. FIG. 8B depicts an exemplary expanded view of the c[di-GMP] binding pocket in the complex. FIG. 8C depicts an exemplary surface

representation of an exemplary structure of a complex of c[di-GMP] bound to human STING^H232 (aa 139-379) (PDB: 4EF4) with the same color-coding as in Figure 1A. FIG. 8D depicts an exemplary view in panel C rotated through 90°. FIG. 8E and FIG. 8F depicts exemplary intermolecular contacts in the complex of c[di-GMP] bound to hSTING^H232. The bound cyclic c[di-GMP] is shown in biscuit color, with individual STING subunits in the symmetrical dimer shown in magenta and yellow. The intermolecular contacts to the base edges of the ligand by the magenta and yellow subunits of STING are shown in panel E, while the intermolecular contacts to the backbone phosphates of the ligand by STING are shown in panel F.

[0038] Figure 9 depicts exemplary details of c[G(2',5')pA(2',5')p]-hSTING^H232 and c[G(3',5')pA(3',5')p]-mSting^R231 complexes. FIG. 9A depicts an exemplary superposition of the c[G(2',5')pA(2',5')p] (both subunits in red) and c[G(2',5')pA(3',5')p] (both subunits in green) bound structures of hSTING^H232 (aa 155-341). FIG. 9B depicts exemplary details of hydrogen- bonding interactions in the structure of the c[G(2',5')pA(2',5')p]-hSTING^H232 complex. Note the water-mediated hydrogen bonds between the 3' -OH groups and side chains of SI 62 and T267. FIG. 9C depicts an exemplary superposition of the c[G(3',5')pA(3',5')p] (both subunits in cyan) and c[G(2',5')pA(3',5')p] (both subunits in magenta) bound structures of mSting^R231 (aa 154- 340). FIG. 9D depicts exemplary details of hydrogen-bonding interactions in the structure of the c[G(3',5')pA(3',5')p]-mSting^R231 complex. Note the direct hydrogen bonds between the 2'-OH groups and the side chains of T262. FIG. 9E depicts an exemplary superposition of the c[G(2',5')pA(2',5')p] in its complex with hSTING^H232 in red and c[G(3',5 ')pA(3',5')p] in its complex with mSTING^R231 in cyan. The c[G(2',5')pA(2',5')p] is positioned deeper in the binding pocket than is its c[G(3',5')pA(3',5')p] counterpart.

[0039] Figure 10 depicts exemplary an exemplary crystal structure of CMA ligand bound to mSting^R231. FIG. 10A depicts an exemplary chemical formula of lO-carboxymethyl-9- acridine (CMA). FIG. 10B depicts an exemplary superposition of the 2.90 A DMXAA-bound structure of mSting^R231 (aa 154-340) with both subunits in biscuit and 2.75 A CMA-bound structure of mSting^R231 (aa 149-348) with both subunits in yellow (PDB: 4JC5).

[0040] Figure 11 depicts an exemplary experiment of cGAMP stimulation of BMDMs from wild-type and mutant STING mice. BMDMs from wild-type mice (Sting^+/+) and the N- ethyl-N-nitrosourea (ENU)-induced Goldenticket (Gt) mutant mice (Sting ) were generated. Cells (1 x 10⁶) were treated with cGAMP linkage isomers, c[G(2',5')pA(2',5')p], c[G(2',5')pA(3',5')p] and c[G(3',5')pA(3',5')p] at a final concentration of 15 μΜ. As before, cGAMP linkage isomers were provided by addition into media. Cells were collected at 2, 4, and 8 h post-treatment. Mock treatment controls were included (0 h). Western blot analysis was performed with anti-phosphoserine-396 of IRF3 or anti-IRF3, anti-phosphoserine-172 of TBKl and anti-TBKl . Glyceraldehyde 3-phosphate dehydrogenase (Gapdh) was used as a loading control.

[0041] Figure 12 depicts exemplary results showing that STING point mutants and natural STING variants display distinct dose-responses to cGAMP linkage isomers. The dotted line indicates the 5 μΜ cGAMP dose, whose corresponding values are that shown in Figure 7. For dose dependence: Data points were determined in triplicate and are depicted as means ± SEM. FIG. 12A, FIG. 12B, FIG. 12C, FIG. 12D, FIG. 12E, FIG. 12F and FIG. 12G depicts exemplary results showing HEK293T cells were transfected with human (panels A-F) or murine (panel G) STING variants for 12 h and cGAMP isomers delivered by Digitonin permeabilization (30 min) were titrated as indicated. Luciferase values were determined 12 h after stimulation.

[0042] Figure 13 depicts exemplary results showing that the S162A point mutation acquires DMXAA responsiveness in both hSTING^H232 and hSTING^R232 variants. HEK293T cells were transfected with human STING variants and murine STING as indicated, and 12 h later incubated with DMXAA without permeabilization or stimulated with c[di-GMP] and cGAMP isomers following digitonin permeabilization (30 min). Luciferase values were determined 12 h after stimulation. Panels A and B show human STING^H232 and STING^R232, panels C and D show the respective S162A mutants. In panel E responsiveness of murine Sting to DMXAA, c[di- GMP] and cGAMP isomers is shown for comparison. For dose dependence: Data points were determined in triplicate and are depicted as means ± SEM.

[0043] Figure 14 depicts exemplary results of hSTING position 162 variants and their sensitivity to cyclic dinucleaotides and DMXAA. 293T cells were transfected with reporter plasmids and hSTING variants as indicated. 12 h after transfection, cells were stimulated by incubation with 75 μg/ml DMXAA (panel A) or Digitonin-permeabilized for 30 min in the presence of cyclic dinucleotides (5μΜ) as indicated (panel B). After another 12h, cells were lysed and luciferase assay was performed. For bar graphs: Data points were determined in triplicate and are depicted as means ± SEM. FIG. 14A depicts an exemplary result showing conversion of SI 62 to Ala in H232 or R232 hSTING background renders the protein sensitive to DMXAA stimulation. However, substitution by VI 62 or 1162 does not yield similar results with DMXAA. FIG. 14B depicts an exemplary result showing conversion of SI 62 to Ala in H232 or R232 hSTING background does not significantly affect the respective protein sensitivities to cGAMP linkage isomers or c-[di-GMP]. Substitution by VI 62 or 1162 reduces/eliminates stimulation by any cyclic dinucleotide.

[0044] Figure 15 depicts exemplary results of how the replacement of non-conserved residues of hSTING with its murine counterparts enables recognition of DMXAA, as well as a crystal structure of DMXAA bound to hSTING^group2 and details of intermolecular interactions in the complex. FIG. 15A depicts the chemical formula of 5,6-dimethyl-xanthenone-4-acetic acid (DMXAA). FIGS. 15C-D depict isothermal titration calorimetry (ITC) binding curves for complex formation between DMXAA bound to hSTING^group1234 (aa 140-379) (panel B) and hSTING^group2 (panel C). FIG. 15D depicts 293T cells were transfected with IFN-β reporter constructs and STING variants as indicated. 12 hours after transfection, cells were stimulated with 0.18 mM DMXAA (50 μg/ml). Luciferase activity was determined after another 12 hours. Dotted lines separate (from left to right) wt controls, single group mutants, hSTING^group1234 and triple group mutants. Shown are raw values of Gaussia luciferase activity normalized to constitutive Firefly luciferase values. Values depicted are the means of triplicates +SEM and representative of 3 independent experiments. FIG. 15E depicts the 1.88 A crystal structure of DMXAA bound to hSTING^group2 (aa 155-341). The symmetrical hSTING^group2 dimer is shown in a ribbon representation. The DMXAA in a space-filling representation is bound in the central cavity at the interface between the two monomers. FIG. 15F depicts intermolecular contacts in the complex. The bound DMXAA is shown with individual STING subunits in the symmetrical dimer. FIG. 15G depicts two expanded views of the hydrophobic interactions of the G230I substitution in the complex (box region in panel E). Other residues lining the hydrophobic pocket are shown in a lighter shade.

[0045] Figure 16 depicts that G230 in hSTING and 1229 in mSTING are relevant for

DMXAA species selectivity. FIG. 16A depicts results where 293T cells were transfected with IFN-β reporter constructs and STING variants as indicated. 12 hours after transfection, cells were stimulated with ascending concentrations of DMXAA. Luciferase activity was determined after another 12 hours. Shown are the means of triplicates +SEM, representative of 3

independent experiments. FIG. 16B depicts results where 293T cells were transfected with mSTING variants and reporter constructs. Stimulation and luciferase assay was performed as described in panel A. Dose-responses are representative of 2 independent experiments. FIG. 16C depicts the 2.51 A crystal structure of DMXAA bound to hSTINGG230I (aa 155-341). The representations are the same as used in Figure 15E. FIG. 16D depicts detailed hydrophobic interactions in the complex of DMXAA bound to hSTINGG230I, with the same representations as in Figure 15G.

[0046] Figure 17 depicts exemplary results showing S162A and Q266I substitutions render hSTING sensitive to DMXAA. FIG. 17A depicts results where A293T cells were transfected with reporter constructs and indicated hSTING variants. 12 hours after transfection, cells were stimulated with 0.18 mM DMXAA for another 12 hours, followed by luciferase assay. Shown are means of triplicates +SEM, representative of 3 independent experiments. FIG. 17B depicts DMXAA dose-response curves of 293T cells transfected with indicated STING variants and illustrating one representative of 3 independent experiments. FIG. 17C depicts an ITC binding curve for complex formation between DMXAA bound to hSTINGS162A/Q266I (aa 140-379). FIG. 17D depicts natural variants of hSTING (Yi et al, 2013). Five hSTING variants (shown in the left column) were studied in this work. The amino acid variations are shown in the right column. FIG. 17E depicts results where 293T cells were transfected and stimulated as in (A). Shown are S162A and Q266I mutants of major human STING alleles. WT denotes the respective allele in this context. Shown are the means of triplicates +SEM, representative of 3 independent experiments. FIG. 17F depicts the 2.42 A crystal structure of DMXAA bound to hSTINGS162A/Q266I (aa 155-341). The representations are the same as used in Figure 15E. FIG. 17G depicts two alternate views of the hydrophobic interactions of DMXAA with hSTINGS162A/Q266I. The two bound DMXAA molecules are shown in space-filling representation, with surrounded hydrophobic side chains shown in stick and dot representations. [0047] Figure 18 depicts findings that triple substitution of G230I/S 162A/Q266I yields an hSTING Variant with higher affinity to DMXAA compared to mSTING, and robust stimulation of cytokines/chemokines in mouse cells. FIG. 18A depicts an ITC binding curve for complex formation between DMXAA bound to STING^{sl62A/G230I/Q2661} (aa 140-379). FIG. 18B depicts results where 293T cells were transfected with reporter constructs and indicated STING variants. After 12 hours, cells were stimulated with ascending concentrations of DMXAA for another 12 hours, followed by luciferase assay. Individual data points are means of triplicates ±SEM. Representative of 3 independent experiments. FIG. 18C depicts the 2.37 A crystal structure of DMXAA bound to STING^{sl62A G230I/Q2661} (aa 155-341). The representations are the same as used in Figure 15E. FIG. 18D depicts hydrophobic interactions of G230I substitution in the complex of DMXAA bound to STING^{sl62A/G230I/Q2661}. The representations are the same as used in Figure 15G. FIG. 18E depicts hydrophobic interactions of DMXAA in the ligand- binding pocket, with the same representations as Figure 17G. FIG. 18F depicts results where BMDCs (lxl 0⁶) from STING^Gt/Gt mouse were transduced with retroviruses expressing wt and various hSTING mutants. Two days afterviral infection, BMDCs were treated with 5(^g/ml of DMXAA for 3 hours and cells were collected for real-time PCR to measure IFN-β, CXCL10, CCL5 and IL-6 mRNA levels. Data shown are means ± SEM (n=3), representative of two independent experiments. FIG. 18G depicts results where BMDCs were transfected with retroviruses expressing wt hSTING and various hSTING mutants. Cells were collected 2 days after retroviral infection, and the levels of hSTING were determined by Western blot analysis.

[0048] Figure 19 depicts sequence alignment of STING from mouse and human and the design of group substituents. The transmembrane domain (1-139 of hSTING; 1-138 of mSTING) and C-terminal domian (140-379 of hSTING; 139-378 of mSTING) are shown in gray and black, respectively. The group substituents are indicated in boxes. Arrows indicate the mutated residues within the ligand-binding pocket.

[0049] Figure 20 depicts ITC binding assays for DMXAA with hSTING group 1 , group3 , and group4 mutants and structural comparison of DMXAA Bound to hSTINGgroup2 and mSTING. FIG. 20A depicts ITC binding curves for complex formation between DMXAA bound to hSTINGgroupl (aa 140-379) (left), hSTINGgroup3 (middle), and hSTINGgroup4 (right). FIG. 20B depicts superposed structures of the complex of DMXAA bound with mSTING (PDB: 4LOL) and hSTINGgroup2 (aa 155-341). FIG. 20C depicts hydrophobic interactions of 1229 with surrounding residues in the mSTING-DMXAA complex, with the same representations used in Figure 15G.

[0050] Figure 21 depicts a structural comparison of DMXAA Bound to hSTING⁰²³⁰¹ and hSTING^group2, as well as ITC-based DMXAA-binding assays for hSTING S162A and Q266I Mutants. FIG. 21A depicts exemplary intermolecular contacts in the complex of DMXAA bound to hSTING⁰²³⁰¹ (aa 155-341). The bound DMXAA is shown with individual STING subunits in the symmetrical dimer. FIG. 21B depicts superposed structures of the complex of DMXAA bound with hSTING⁰²³⁰¹ (aa 155-341) and hSTING^group2 (aa 155-341). FIGS. 21C-D depict ITC binding curves for complex formation between DMXAA bound to hSTING^sl62A (aa 140-379) (panel C) and hSTING^Q2661 (panel D).

[0051] Figure 22 depicts dose-responses of hSTING Variants and their respective

S162A, Q266I Mutants to DMXAA and the structural comparison of DMXAA bound to hSTING⁰²³⁰¹ and STING^sl62A/Q2661, as well as DMXAA stimulation of cytokines/chemokines in mouse cells. 293T cells were transfected with reporter constructs and indicated STING variants. After 12 hours, cells were stimulated with ascending concentration of DMXAA (A and B) directly added to medium. Luciferase assay was performed after another 12 hours. Dose- responses shown are representative of 2 independent experiments. FIG. 22 A depicts DMXAA dose-response of hSTING variants with S162A, Q266I double substituent. For improved clarity, only hSTING^H232 is shown as a representative for the corresponding wt variants. Circle refers to magnified view in (B). FIG. 22B depicts DMXAA dose-responses of hSTING^HAQ and hSTING^HAQ S162A, Q266I on a magnified scale (circle denotes corresponding hSTING^HAQ S162A, Q266I curve in (A)). FIG. 22C depicts superposed structures of the complex of DMXAA bound with hSTING⁰²³⁰¹ (aa 155-341) and STING^{sl62A Q2661} (aa 155-341). FIG. 22D depicts exemplary intermolecular contacts in the complex of DMXAA bound to

hSTING^{sl62A Q2661} (aa 155-341). The bound DMXAA is shown with individual STING subunits in the symmetrical dimer. FIG. 22E depicts results where BMDCs were infected with retroviruses (same as in Figure 18F). Cells were incubated with 50 μg/ml of DMXAA and supematants were collected 18 hours after treatment. CXCLIO protein levels were determined by ELISA. Data shown are means ± SEM (n=3), representative of two independent experiments.

[0052] Figure 23 depicts an exemplary block diagram of a computing device and a mobile computing device.

[0053] Figure 24 depicts an exemplary block diagram of a network environment for establishing a multi-channel context aware communication environment.

Definitions

[0054] Compounds of this invention include those described generally above, and are further illustrated by the classes, subclasses, and species disclosed herein. As used herein, the following definitions shall apply unless otherwise indicated. For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75^th Ed. Additionally, general principles of organic chemistry are described in "Organic Chemistry", Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry", 5^th Ed., Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated by reference.

[0055] The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulae set forth herein are constructed according to the standard rules of chemical valency known in the chemical arts.

[0056] Unless otherwise stated, structures depicted herein are also meant to include all isomeric (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) forms of the structure; for example, the R and S configurations for each asymmetric center, Z and E double bond isomers, and Z and E conformational isomers. Therefore, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the invention. Unless otherwise stated, all tautomeric forms of the compounds of the invention are within the scope of the invention. Additionally, unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures including the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a ¹³C- or ¹⁴C-enriched carbon are within the scope of this invention. Such compounds are useful, for example, as analytical tools, as probes in biological assays, or as therapeutic agents in accordance with the present invention.

[0057] Administration: As used herein, the term "administration" refers to the administration of a composition to a subject. Administration may be by any appropriate route. For example, in some embodiments, administration may be bronchial (including by bronchial instillation), buccal, enteral, interdermal, intra-arterial, intradermal, intragastric, intramedullary, intramuscular, intranasal, intraperitoneal, intrathecal, intravenous, intraventricular, mucosal, nasal, oral, rectal, subcutaneous, sublingual, topical, tracheal (including by intratracheal instillation), transdermal, vaginal and vitreal.

[0058] Aliphatic: As used herein, the term "aliphatic" or "aliphatic group" means a straight-chain (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is completely saturated or that contains one or more units of unsaturation, or a monocyclic hydrocarbon or bicyclic hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic (also referred to herein as "carbocycle,"

"cycloaliphatic" or "cycloalkyl"), that has a single point of attachment to the rest of the molecule. Unless otherwise specified, aliphatic groups contain 1-6 aliphatic carbon atoms. In some embodiments, aliphatic groups contain 1-5 aliphatic carbon atoms. In some embodiments, aliphatic groups contain 1-4 aliphatic carbon atoms. In some embodiments, aliphatic groups contain 1-3 aliphatic carbon atoms, and in yet other embodiments, aliphatic groups contain 1-2 aliphatic carbon atoms. In some embodiments, "cycloaliphatic" (or "carbocycle" or

"cycloalkyl") refers to a monocyclic C3-C6 hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic, that has a single point of attachment to the rest of the molecule. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl. [0059] Alkyl: As used herein, the term "alkyl" refers to saturated, straight- or branched- chain hydrocarbon radicals derived from an aliphatic moiety containing between one and six carbon atoms by removal of a single hydrogen atom. Unless otherwise specified, alkyl groups contain 1-12 carbon atoms. In certain embodiments, alkyl groups contain 1-8 carbon atoms. In certain embodiments, alkyl groups contain 1-6 carbon atoms. In some embodiments, alkyl groups contain 1-5 carbon atoms, in some embodiments, alkyl groups contain 1-4 carbon atoms, in some embodiments alkyl groups contain 1-3 carbon atoms, and in some embodiments alkyl groups contain 1-2 carbon atoms. Examples of alkyl radicals include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, sec-pentyl, iso-pentyl, tert- butyl, n-pentyl, neopentyl, n-hexyl, sec-hexyl, n-heptyl, n-octyl, n-decyl, n-undecyl, dodecyl, and the like.

[0060] Amino acid: As used herein, the term "amino acid," in its broadest sense, refers to any compound and/or substance that can be incorporated into a polypeptide chain, e.g., through formation of one or more peptide bonds. In some embodiments, an amino acid has the general structure H2N-C(H)(R)-COOH. In some embodiments, an amino acid is a naturally- occurring amino acid. In some embodiments, an amino acid is a synthetic amino acid; in some embodiments, an amino acid is a D-amino acid; in some embodiments, an amino acid is an L- amino acid. "Standard amino acid" refers to any of the twenty standard L-amino acids commonly found in naturally occurring peptides. "Nonstandard amino acid" refers to any amino acid, other than the standard amino acids, regardless of whether it is prepared synthetically or obtained from a natural source. In some embodiments, an amino acid, including a carboxy- and/or amino-terminal amino acid in a polypeptide, can contain a structural modification as compared with the general structure above. For example, in some embodiments, an amino acid may be modified by methylation, amidation, acetylation, and/or substitution as compared with the general structure. In some embodiments, such modification may, for example, alter the circulating half life of a polypeptide containing the modified amino acid as compared with one containing an otherwise identical unmodified amino acid. In some embodiments, such modification does not significantly alter a relevant activity of a polypeptide containing the modified amino acid, as compared with one containing an otherwise identical unmodified amino acid. As will be clear from context, in some embodiments, the term "amino acid" is used to refer to a free amino acid; in some embodiments it is used to refer to an amino acid residue of a polypeptide.

[0061] Analog: As used herein, the term "analog" refers to a substance that shares one or more particular structural features, elements, components, or moieties with a reference substance. Typically, an "analog" shows significant structural similarity with the reference substance, for example sharing a core or consensus structure, but also differs in certain discrete ways. In some embodiments, an analog a substance that can be generated from the reference substance by chemical manipulation of the reference substance. In some embodiemnts, an analog is a substance that can be generated through performance of a synthetic process substantially similar to (e.g., sharing a plurality of steps with) one that generates the reference substance. In some embodiments, an analog is or can be generated through performance of a synthetic process different from that used to generate the reference substance.

[0062] Animal: As used herein, the term "animal" refers to any member of the animal kingdom. In some embodiments, "animal" refers to humans, at any stage of development. In some embodiments, "animal" refers to non-human animals, at any stage of development. In some embodiments, the non-human animal is a mammal (e.g., a rodent, a mouse, a rat, a rabbit, a monkey, a dog, a cat, a sheep, cattle, a primate, and/or a pig). In some embodiments, animals include, but are not limited to, mammals, birds, reptiles, amphibians, fish, and/or worms. In some embodiments, an animal may be a transgenic animal, genetically-engineered animal, and/or a clone.

[0063] Approximately: As used herein, the term "approximately" and "about" is intended to encompass normal statistical variation as would be understood by those of ordinary skill in the art as appropriate to the relevant context. In certain embodiments, the term

"approximately" or "about" refers to a range of values that fall within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value). [0064] Associated with: Two events or entities are "associated" with one another, as that term is used herein, if the presence, level and/or form of one is correlated with that of the other. For example, a particular entity (e.g., polypeptide) is considered to be associated with a particular disease, disorder, or condition, if its presence, level and/or form correlates with incidence of and/or susceptibility of the disease, disorder, or condition (e.g., across a relevant population). In some embodiments, two or more entities are physically "associated" with one another if they interact, directly or indirectly, so that they are and remain in physical proximity with one another. In some embodiments, two or more entities that are physically associated with one another are covalently linked to one another; in some embodiments, two or more entities that are physically associated with one another are not covalently linked to one another but are non- covalently associated, for example by means of hydrogen bonds, van der Waals interaction, hydrophobic interactions, magnetism, and combinations thereof.

[0065] Characteristic sequence element: As used herein, the phrase "characteristic sequence element" refers to a sequence element found in a polymer (e.g., in a polypeptide or nucleic acid) that represents a characteristic portion of that polymer. In some embodiments, presence of a characteristic sequence element correlates with presence or level of a particular activity or property of the polymer. In some embodiments, presence (or absence) of a characteristic sequence element defines a particular polymer as a member (or not a member) of a particular family or group of such polymers. A characteristic sequence element typically comprises at least two monomers (e.g., amino acids or nucleotides). In some embodiments, a characteristic sequence element includes at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, or more monomers (e.g., contiguously linked monomers). In some embodiments, a characteristic sequence element includes at least first and second stretches of continguous monomers spaced apart by one or more spacer regions whose length may or may not vary across polymers that share the sequence element. In certain embodiments, particular characteristic sequence elements may be referred to as "motifs".

[0066] Combination therapy: As used herein, the term "combination therapy" refers to those situations in which a subject is simultaneously exposed to two or more therapeutic agents. In some embodiments, such agents are administered simultaneously; in some embodiments, such agents are administered sequentially; in some embodiments, such agents are administered in overlapping regimens.

[0067] Comparable: The term "comparable", as used herein, refers to two or more agents, entities, situations, sets of conditions, etc that may not be identical to one another but that are sufficiently similar to permit comparison therebetween so that conclusions may reasonably be drawn based on differences or similarities observed. Those of ordinary skill in the art will understand, in context, what degree of identity is required in any given circumstance for two or more such agents, entities, situations, sets of conditions, etc to be considered comparable.

[0068] Computer-readable medium: The term "computer-readable medium", as used herein, refers to non-volatile (i.e. secondary storage) computer data storage and/or memory to retain digital data even when not powered. Examples of computer-readable medium include, but are not limited to hard disk, floppy disk, flash memory(i.e. solid state memory), Ferroelectric RAM (F-RAM), Magnetoresistive RAM (MRAM), optical disc, standalone RAM disks, ZIP drives, magenetic tape and holographic memory.

[0069] Computer system: The term "computer system" or "computer", as used herein, refers to a computing device that can be used to implement the techniques described in this disclosure. An exemplary computing device 2500 and a mobile computing device are shown in FIG. 25.

[0070] Corresponding to: As used herein, the term "corresponding to" is often used to designate the position/identity of a residue in a polymer, such as an amino acid residue in a polypeptide or a nucleotide residue in a nucleic acid. Those of ordinary skill will appreciate that, for purposes of simplicity, residues in such a polymer are often designated using a canonical numbering system based on a reference related polymer, so that a residue in a first polymer "corresponding to" a residue at position 190 in the reference polymer, for example, need not actually be the 190^th residue in the first polymer but rather corresponds to the residue found at the 190^th position in the reference polymer; those of ordinary skill in the art readily appreciate how to identify "corresponding" amino acids, including through use of one or more

commercially-available algorithms specifically designed for polymer sequence comparisons. [0071] Crystal structure: As used herein, the term "crystal structure" of a composition shall mean a computer readable medium in which is stored a representation of three dimensional positional information (i.e. coordinates) for atoms of the composition.

[0072] Derivative: As used herein, the term "derivative" refers to a structural analogue of a reference substance. That is, a "derivative" is a substance that shows significant structural similarity with the reference substance, for example sharing a core or consensus structure, but also differs in certain discrete ways. In some embodiments, a derivative is a substance that can be generated from the reference substance by chemical manipulation. In some embodiemnts, a derivative is a substance that can be generated through performance of a synthetic process substantially similar to (e.g., sharing a plurality of steps with) one that generates the reference substance.

[0073] Docking: As used herein, the term "docking" refers to orienting, rotating, translating a chemical entity in the binding pocket, domain, molecule or molecular complex or portion thereof based on distance geometry or energy. Docking may be performed by distance geometry methods that find sets of atoms of a chemical entity that match sets of sphere centers of the binding pocket, domain, molecule or molecular complex or portion thereof. See Meng et al. J. Comp. Chem. 4: 505-524 (1992). Sphere centers are generated by providing an extra radius of given length from the atoms (excluding hydrogen atoms) in the binding pocket, domain, molecule or molecular complex or portion thereof. Real-time interaction energy calculations, energy minimizations or rigid-body minimizations (Gschwend et al., J. Mol. Recognition 9: 175- 186 (1996)) can be performed while orienting the chemical entity to facilitate docking. For example, interactive docking experiments can be designed to follow the path of least resistance. If the user in an interactive docking experiment makes a move to increase the energy, the system will resist that move. However, if that user makes a move to decrease energy, the system will favor that move by increased responsiveness. (Cohen et al, J. Med. Chem. 33:889-894 (1990)). Docking can also be performed by combining a Monte Carlo search technique with rapid energy evaluation using molecular affinity potentials. See Goodsell and Olson, Proteins: Structure, Function and Genetics 8:195-202 (1990). Software programs that carry out docking functions include but are not limited to MATCHMOL (Cory et al, J. Mol. Graphics 2: 39 (1984);

MOLFIT (Redington, Comput. Chem. 16: 217 (1992)) and DOCK (Meng et al, supra).

[0074] Dosage form: As used herein, the term "dosage form" refers to a physically discrete unit of a therapeutic agentfor administration to a subject. Each unit contains a predetermined quantity of active agent. In some embodiments, such quantity is a unit dosage amount (or a whole fraction thereof) appropriate for administration in accordance with a dosing regimen that has been determined to correlate with a desired or beneficial outcome when administered to a relevant population (i.e., with a therapeutic dosing regimen).

[0075] Designed: As used herein, the term "designed" refers to an agent (i) whose structure is or was selected by the hand of man; (ii) that is produced by a process requiring the hand of man; and/or (iii) that is distinct from natural substances and other known agents.

[0076] Dosing regimen: As used herein, the term "dosing regimen" refers to a set of unit doses (typically more than one) that are administered individually to a subject, typically separated by periods of time. In some embodiments, a given therapeutic agent has a

recommended dosing regimen, which may involve one or more doses. In some embodiments, a dosing regimen comprises a plurality of doses each of which are separated from one another by a time period of the same length; in some embodiments, a dosing regimen comprises a plurality of doses and at least two different time periods separating individual doses. In some embodiments, a dosing regimen is correlated with a desired or beneficial outcome when administered across a relevant population (i.e., is a therapeutic dosing regimen).

[0077] Engineered: In general, the term "engineered" refers to the aspect of having been manipulated by the hand of man. For example, a polynucleotide is considered to be

"engineered" when two or more sequences, that are not linked together in that order in nature, are manipulated by the hand of man to be directly linked to one another in the engineered polynucleotide. For example, in some embodiments of the present invention, an engineered polynucleotide comprises a regulatory sequence that is found in nature in operative association with a first coding sequence but not in operative association with a second coding sequence, is linked by the hand of man so that it is operatively associated with the second coding sequence. Comparably, a cell or organism is considered to be "engineered" if it has been manipulated so that its genetic information is altered (e.g., new genetic material not previously present has been introduced, for example by transformation, mating, somatic hybridization, transfection, transduction, or other mechanism, or previously present genetic material is altered or removed, for example by substitution or deletion mutation, or by mating protocols). As is common practice and is understood by those in the art, progeny of an engineered polynucleotide or cell are typically still referred to as "engineered" even though the actual manipulation was performed on a prior entity.

[0078] Fragment: A "fragment" of a material or entity as described herein has a structure that includes a discrete portion of the whole, but lacks one or more moieties found in the whole. In some embodiments, a fragment consists of such a discrete portion. In some embodiments, a fragment consists of or comprises a characteristic structural element or moiety found in the whole. In some embodiments, a polymer fragment comprises or consists of at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500 or more monomeric units (e.g., residues) as found in the whole polymer. In some embodiments, a polymer fragment comprises or consists of at least about 5%, 10%, 15%, 20%, 25%, 30%, 25%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more of the monomeric units (e.g., residues) found in the whole polymer. The whole material or entity may in some embodiments be referred to as the "parent" of the whole.

[0079] Homology: As used herein, the term "homology" refers to the overall relatedness between polymeric molecules, e.g., between nucleic acid molecules (e.g., DNA molecules and/or RNA molecules) and/or between polypeptide molecules. In some embodiments, polymeric molecules are considered to be "homologous" to one another if their sequences are at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical. In some embodiments, polymeric molecules are considered to be "homologous" to one another if their sequences are at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%), 80%), 85%o, 90%), 95%, or 99% similar (e.g., containing residues with related chemical properties at corresponding positions). For example, as is well known by those of ordinary skill in the art, certain amino acids are typically classified as similar to one another as "hydrophobic" or "hydrophilic"amino acids, and/or as having "polar" or "non-polar" side chains. Substitution of one amino acid for another of the same type may often be considered a "homologous" substitution. Typical amino acid categorizations are summarized below:

Valine Val V nonpolar neutral 4.2

[0080] As will be understood by those skilled in the art, a variety of algorithms are available that permit comparison of sequences in order to determine their degree of homology, including by permitting gaps of designated length in one sequence relative to another when considering which residues "correspond" to one another in different sequences. Calculation of the percent homology between two nucleic acid sequences, for example, can be performed by aligning the two sequences for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second nucleic acid sequences for optimal alignment and non- corresponding sequences can be disregarded for comparison purposes). In certain embodiments, the length of a sequence aligned for comparison purposes is at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or substantially 100% of the length of the reference sequence. The nucleotides at corresponding nucleotide positions are then compared. When a position in the first sequence is occupied by the same nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position; when a position in the first sequence is occupied by a similar nucleotide as the corresponding position in the second sequence, then the molecules are similar at that position. The percent homology between the two sequences is a function of the number of identical and similar positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which needs to be introduced for optimal alignment of the two sequences.

Representative algorithms and computer programs useful in determining the percent homology between two nucleotide sequences include, for example, the algorithm of Meyers and Miller (CABIOS, 1989, 4: 11-17), which has been incorporated into the ALIGN program (version 2.0) using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. The percent homology between two nucleotide sequences can, alternatively, be determined for example using the GAP program in the GCG software package using an NWSgapdna.CMP matrix.

[0081] Homology model: As used herein, the term "homology model" refers to a set of coordinates derived from known three-dimensional structure used as template. Generation of the homology model, termed "homology modeling", involves sequence alignment, residue replacement and residue conformation adjustment through energy minimization.

[0082] Human: In some embodiments, a human is an embryo, a fetus, an infant, a child, a teenager, an adult, or a senior citizen.

[0083] Hydrophilic: As used herein, the term "hydrophilic" and/or "polar" refers to a tendency to mix with, or dissolve easily in, water.

[0084] Hydrophobic: As used herein, the term "hydrophobic" and/or "non-polar", refers to a tendency to repel, not combine with, or an inability to dissolve easily in, water.

[0085] Identity: As used herein, the term "identity" refers to the overall relatedness between polymeric molecules, e.g., between nucleic acid molecules (e.g., DNA molecules and/or R A molecules) and/or between polypeptide molecules. In some embodiments, polymeric molecules are considered to be "substantially identical" to one another if their sequences are at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% identical. As will be understood by those skilled in the art, a variety of algorithms are available that permit comparison of sequences in order to determine their degree of homology, including by permitting gaps of designated length in one sequence relative to another when considering which residues "correspond" to one another in different sequences. Calculation of the percent identity between two nucleic acid sequences, for example, can be performed by aligning the two sequences for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second nucleic acid sequences for optimal alignment and non- corresponding sequences can be disregarded for comparison purposes). In certain embodiments, the length of a sequence aligned for comparison purposes is at least 30%>, at least 40%>, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or substantially 100% of the length of the reference sequence. The nucleotides at corresponding nucleotide positions are then compared. When a position in the first sequence is occupied by the same nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which needs to be introduced for optimal alignment of the two sequences. Representative algorithms and computer programs useful in determinng the percent identity between two nucleotide sequences include, for example, the algorithm of Meyers and Miller (CABIOS, 1989, 4: 11-17), which has been incorporated into the ALIGN program (version 2.0) using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. The percent identity between two nucleotide sequences can, alternatively, be determined for example using the GAP program in the GCG software package using an NWSgapdna.CMP matrix.

[0086] Inhibition model: As used herein, the term "inhibition model" refers to a region or regions of proteins that can associate with another chemical entity or compound. Such regions are of significant utility in fields such as drug discovery. These regions are formed by amino acid residues key for ligand binding or may be residues that are spatially related and define a three-dimensional shape of the binding pocket. In some embodiments, the amino acid residues may be contiguous or non-contiguous in primary sequence. In some embodiments, the region or regions may be embodied as a dataset (e.g. an array of structure coordinates) recorded on computer readable media.

[0087] Isolated: As used herein, the term "isolated" refers to a substance and/or entity that has been (1) separated from at least some of the components with which it was associated when initially produced (whether in nature and/or in an experimental setting), and/or (2) designed, produced, prepared, and/or manufactured by the hand of man. Isolated substances and/or entities may be separated from about 10%>, about 20%>, about 30%>, about 40%>, about 50%, about 60%, about 70%, about 80%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% of the other components with which they were initially associated. In some embodiments, isolated agents are about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% pure. As used herein, a substance is "pure" if it is substantially free of other components. In some embodiments, as will be understood by those skilled in the art, a substance may still be considered "isolated" or even "pure", after having been combined with certain other components such as, for example, one or more carriers or excipients (e.g., buffer, solvent, water, etc.); in such embodiments, percent isolation or purity of the substance is calculated without including such carriers or excipients. In some embodiments, isolation involves or requires disruption of covalent bonds (e.g., to isolate a polypeptide domain from a longer polypeptide and/or to isolate a nucleotide sequence element from a longer oligonucleotide or nucleic acid).

[0088] Modulator: The term "modulator" is used to refer to an entity whose presence in a system in which an activity of interest is observed correlates with a change in level and/or nature of that activity as compared with that observed under otherwise comparable conditions when the modulator is absent. In some embodiments, a modulator is an activator, in that activity is increased in its presence as compared with that observed under otherwise comparable conditions when the modulator is absent. In some embodiments, a modulator is an inhibitor, in that activity is reduced in its presence as compared with otherwise comparable conditions when the modulator is absent. In some embodiments, a modulator interacts directly with a target entity whose activity is of interest. In some embodiments, a modulator interacts indirectly (i.e., directly with an intermediate agent that interacts with the target entity) with a target entity whose activity is of interest. In some embodiments, a modulator affects level of a target entity of interest; alternatively or additionally, in some embodiments, a modulator affects activity of a target entity of interest without affecting level of the target entity. In some embodiments, a modulator affects both level and activity of a target entity of interest, so that an observed difference in activity is not entirely explained by or commensurate with an observed difference in level.

[0089] Nucleic acid: As used herein, the term "nucleic acid," in its broadest sense, refers to any compound and/or substance that is or can be incorporated into an oligonucleotide chain. In some embodiments, a nucleic acid is a compound and/or substance that is or can be incorporated into an oligonucleotide chain via a phosphodiester linkage. As will be clear from context, in some embodiments, "nucleic acid" refers to individual nucleic acid residues (e.g., nucleotides and/or nucleosides); in some embodiments, "nucleic acid" refers to an

oligonucleotide chain comprising individual nucleic acid residues. In some embodiments, a "nucleic acid" is or comprises RNA; in some embodiments, a "nucleic acid" is or comprises DNA. In some embodiments, a nucleic acid is, comprises, or consists of one or more natural nucleic acid residues. In some embodiments, a nucleic acid is, comprises, or consists of one or more nucleic acid analogs. In some embodiments, a nuclic acid analog differs from a nucleic acid in that it does not utilize a phosphodiester backbone. For example, in some embodiments, a nucleic acid is, comprises, or consists of one or more "peptide nucleic acids", which are known in the art and have peptide bonds instead of phosphodiester bonds in the backbone, are considered within the scope of the present invention. Alternatively or additionally, in some embodiments, a nucleic acid has one or more phosphorothioate and/or 5'-N-phosphoramidite linkages rather than phosphodiester bonds. In some embodiments, a nucleic acid is, comprises, or consists of one or more natural nucleosides (e.g., adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxyguanosine, and deoxy cytidine). In some embodiments, a nucleic acid is, comprises, or consists of one or more nucleoside analogs (e.g., 2- aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine, 3-methyl adenosine, 5- methylcytidine, C-5 propynyl-cytidine, C-5 propynyl-uridine, 2-aminoadenosine, C5- bromouridine, C5-fluorouridine, C5-iodouridine, C5-propynyl-uridine, C5-propynyl-cytidine, C5-methylcytidine, 2-aminoadenosine, 7-deazaadenosine, 7-deazaguanosine, 8-oxoadenosine, 8- oxoguanosine, 0(6)-methylguanine, 2-thiocytidine, methylated bases, intercalated bases, and combinations thereof). In some embodiments, a nucleic acid comprises one or more modified sugars (e.g., 2'-fluororibose, ribose, 2'-deoxyribose, arabinose, and hexose) as compared with those in natural nucleic acids. In some embodiments, a nucleic acid has a nucleotide sequence that encodes a functional gene product such as an RNA or protein. In some embodiments, a nucleic acid includes one or more introns. In some embodiments, nucleic acids are prepared by one or more of isolation from a natural source, enzymatic synthesis by polymerization based on a complementary template (in vivo or in vitro), reproduction in a recombinant cell or system, and chemical synthesis. In some embodiments, a nucleic acid is at least 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 20, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000 or more residues long.

[0090] Patient: As used herein, the term "patient" or "subject" refers to a human or any non-human animal (e.g., mouse, rat, rabbit, dog, cat, cattle, swine, sheep, horse or primate) to whom therapy is administered. In many embodiments, a patient is a human being. In some embodiments, a patient is a human presenting to a medical provider for diagnosis or treatment of a disease, disorder or condition. In some embodiments, a patient displays one or more symptoms or characteristics of a disease, disorder or condition. In some embodiments, a patient does not display any symptom or characteristic of a disease, disorder, or condition. In some

embodiments, a patient is someone with one or more features characteristic of susceptibility to or risk of a disease, disorder, or condition.

[0091] Pharmaceutically acceptable: The term "pharmaceutically acceptable" as used herein, refers to agents that, within the scope of sound medical judgment, are suitable for use in contact with tissues of human beings and/or animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.

[0092] Polypeptide: The term "polypeptide", as used herein, generally has its art- recognized meaning of a polymer of at least three amino acids, linked to one another by peptide bonds. In some embodiments, the term is used to refer to specific functional classes of polypeptides, such as, for example, autoantigen polypeptides, nicotinic acetylcholine receptor polypeptides, alloantigen polypeptides, etc. For each such class, the present specification provides several examples of amino acid sequences of known exemplary polypeptides within the class; in some embodiments, such known polypeptides are reference polypeptides for the class. In such embodiments, the term "polypeptide" refers to any member of the class that shows significant sequence homology or identity with a relevant reference polypeptide. In many embodiments, such member also shares significant activity with the reference polypeptide. For example, in some embodiments, a member polypeptide shows an overall degree of sequence homology or identity with a reference polypeptide that is at least about 30-40%, and is often greater than about 50%, 60%, 70%, 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more and/or includes at least one region (i.e., a conserved region, often including a characteristic sequence element) that shows very high sequence identity, often greater than 90% or even 95%, 96%, 97%, 98%, or 99%. Such a conserved region usually encompasses at least 3- 4 and often up to 20 or more amino acids; in some embodiments, a conserved region

encompasses at least one stretch of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more contiguous amino acids. In some embodiments, a useful polypeptide as described herein may comprise or consist of a fragment of a parent polypeptide. In some embodiments, a useful polypeptide as described herein may comprise or consist of a plurality of fragments, each of which is found in the same parent polypeptide in a different spatial arrangement relative to one another than is found in the polypeptide of interest (e.g., fragments that are directly linked in the parent may be spatially separated in the polypeptide of interest or vice versa, and/or fragments may be present in a different order in the polypeptide of interest than in the parent), so that the polypeptide of interest is a derivative of its parent polypeptide.

[0093] Protein: As used herein, the term "protein" refers to a polypeptide {i.e., a string of at least two amino acids linked to one another by peptide bonds). Proteins may include moieties other than amino acids {e.g., may be glycoproteins, proteoglycans, etc.) and/or may be otherwise processed or modified. Those of ordinary skill in the art will appreciate that a

"protein" can be a complete polypeptide chain as produced by a cell (with or without a signal sequence), or can be a characteristic portion thereof. Those of ordinary skill will appreciate that a protein can sometimes include more than one polypeptide chain, for example linked by one or more disulfide bonds or associated by other means. Polypeptides may contain L-amino acids, D- amino acids, or both and may contain any of a variety of amino acid modifications or analogs known in the art. Useful modifications include, e.g., terminal acetylation, amidation, methylation, etc. In some embodiments, proteins may comprise natural amino acids, non-natural amino acids, synthetic amino acids, and combinations thereof. The term "peptide" is generally used to refer to a polypeptide having a length of less than about 100 amino acids, less than about 50 amino acids, less than 20 amino acids, or less than 10 amino acids. In some embodiments, proteins are antibodies, antibody fragments, biologically active portions thereof, and/or characteristic portions thereof. [0094] Reference: The term "reference" is often used herein to describe a standard or control agent or value against which an agent or value of interest is compared. In some embodiments, a reference agent is tested and/or a reference value is determined substantially simultaneously with the testing or determination of the agent or value of interest. In some embodiments, a reference agent or value is a historical reference, optionally embodied in a tangible medium. Typically, as would be understood by those skilled in the art, a reference agent or value is determined or characterized under conditions comparable to those utilized to determine or characterize the agent or value of interest.

[0095] Small molecule: As used herein, the term "small molecule" means a low molecular weight organic compound that may serve as an enzyme substrate or regulator of biological processes. In general, a "small molecule" is a molecule that is less than about 5 kilodaltons (kD) in size. In some embodiments, provided nanoparticles further include one or more small molecules. In some embodiments, the small molecule is less than about 4 kD, 3 kD, about 2 kD, or about 1 kD. In some embodiments, the small molecule is less than about 800 daltons (D), about 600 D, about 500 D, about 400 D, about 300 D, about 200 D, or about 100 D. In some embodiments, a small molecule is less than about 2000 g/mol, less than about 1500 g/mol, less than about 1000 g/mol, less than about 800 g/mol, or less than about 500 g/mol. In some embodiments, one or more small molecules are encapsulated within the nanoparticle. In some embodiments, small molecules are non-polymeric. In some embodiments, in accordance with the present invention, small molecules are not proteins, polypeptides, oligopeptides, peptides, polynucleotides, oligonucleotides, polysaccharides, glycoproteins, proteoglycans, etc. In some embodiments, a small molecule is a therapeutic. In some embodiments, a small molecule is an adjuvant. In some embodiments, a small molecule is a drug.

[0096] Specific: The term "specific", when used herein with reference to an agent or entity having an activity, is understood by those skilled in the art to mean that the agent or entity discriminates between potential targets or states. For example, an agent is said to bind

"specifically" to its target if it binds preferentially with that target in the presence of competing alternative targets. In some embodiments, the agent or entity does not detectably bind to the competing alternative target under conditions of binding to its target. In some embodiments, the agent or entity binds with higher on-rate, lower off-rate, increased affinity, decreased dissociation, and/or increased stability to its target as compared with the competing alternative target(s).

[0097] Storage environment: As used herein, the term "storage environment" comprises any environment comprising secondary storage, i.e. long-term persistent storage. In some embodiments, a storage environment comprises computer-readable medium. In some embodiments, a storage environment comprises a network environment for establishing a multichannel context aware communication environment (i.e. cloud computing). For example, FIG. 23 is a block diagram of a network environment for establishing a multi-channel context aware communication environment.

[0098] Subject: As used herein, the term "subject" refers to a human or any non-human animal (e.g., mouse, rat, rabbit, dog, cat, cattle, swine, sheep, horse or primate). A human includes pre and post natal forms. In many embodiments, a subject is a human being. A subject can be a patient, which refers to a human presenting to a medical provider for diagnosis or treatment of a disease. A subject can be afflicted with or is susceptible to a disease or disorder but may or may not display symptoms of the disease or disorder.

[0099] Substantially: As used herein, the term "substantially" refers to the qualitative condition of exhibiting total or near-total extent or degree of a characteristic or property of interest. One of ordinary skill in the biological arts will understand that biological and chemical phenomena rarely, if ever, go to completion and/or proceed to completeness or achieve or avoid an absolute result. The term "substantially" is therefore used herein to capture the potential lack of completeness inherent in many biological and chemical phenomena.

[0100] Suffering from: An individual who is "suffering from" a disease, disorder, or condition has been diagnosed with and/or exhibits or has exhibited one or more symptoms or characteristics of the disease, disorder, or condition.

[0101] Susceptible to: An individual who is "susceptible to" a disease, disorder, or condition is at risk for developing the disease, disorder, or condition. In some embodiments, an individual who is susceptible to a disease, disorder, or condition does not display any symptoms of the disease, disorder, or condition. In some embodiments, an individual who is susceptible to a disease, disorder, or condition has not been diagnosed with the disease, disorder, and/or condition. In some embodiments, an individual who is susceptible to a disease, disorder, or condition is an individual who has been exposed to conditions associated with development of the disease, disorder, or condition. In some embodiments, a risk of developing a disease, disorder, and/or condition is a population-based risk (e.g., family members of individuals suffering from allergy, etc.

[0102] Symptoms are reduced: According to the present invention, "symptoms are reduced" when one or more symptoms of a particular disease, disorder or condition is reduced in magnitude {e.g., intensity, severity, etc.) and/or frequency. For purposes of clarity, a delay in the onset of a particular symptom is considered one form of reducing the frequency of that symptom.

[0103] Therapeutic agent: As used herein, the phrase "therapeutic agent" refers to any agent that has a therapeutic effect and/or elicits a desired biological and/or pharmacological effect, when administered to a subject. In some embodiments, an agent is considered to be a therapeutic agent if its administration to a relevant population is statistically correlated with a desired or beneficial therapeutic outcome in the population, whether or not a particular subject to whom the agent is administered experiences the desired or beneficial therapeutic outcome.

[0104] Therapeutically effective amount: As used herein, the term "therapeutically effective amount" means an amount that is sufficient, when administered to a population suffering from or susceptible to a disease, disorder, and/or condition in accordance with a therapeutic dosing regimen, to treat the disease, disorder, and/or condition {e.g., allergy). In some embodiments, a therapeutically effective amount is one that reduces the incidence and/or severity of, and/or delays onset of, one or more symptoms of the disease, disorder, and/or condition. Those of ordinary skill in the art will appreciate that the term "therapeutically effective amount" does not in fact require successful treatment be achieved in a particular individual. Rather, a therapeutically effective amount may be that amount that provides a particular desired pharmacological response in a significant number of subjects when

administered to patients in need of such treatment. It is specifically understood that particular subjects may, in fact, be "refractory" to a "therapeutically effective amount." To give but one example, a refractory subject may have a low bioavailability such that clinical efficacy is not obtainable. In some embodiments, reference to a therapeutically effective amount may be a reference to an amount as measured in one or more specific tissues (e.g., a tissue affected by the disease, disorder or condition) or fluids (e.g., blood, saliva, serum, sweart, tears, urine, etc). Those of ordinary skill in the art will appreciate that, in some embodiments, a therapeutically effective agent may be formulated and/or administered in a single dose. In some embodiments, a therapeutically effective agent may be formulated and/or administered in a plurality of doses, for example, as part of a dosing regimen.

[0105] Therapeutic regimen: A "therapeutic regimen", as that term is used herein, refers to a dosing regimen whose administration across a relevant population is correlated with a desired or beneficial therapeutic outcome.

[0106] Treatment: As used herein, the term "treatment" (also "treat" or "treating") refers to any administration of a substance that partially or completely alleviates, ameliorates, relives, inhibits, delays onset of, reduces severity of, and/or reduces frequency, incidence or severity of one or more symptoms, features, and/or causes of a particular disease, disorder, and/or condition. Such treatment may be of a subject who does not exhibit signs of the relevant disease, disorder and/or condition and/or of a subject who exhibits only early signs of the disease, disorder, and/or condition. Alternatively or additionally, such treatment may be of a subject who exhibits one or more established signs of the relevant disease, disorder and/or condition. In some embodiments, treatment may be of a subject who has been diagnosed as suffering from the relevant disease, disorder, and/or condition. In some embodiments, treatment may be of a subject known to have one or more susceptibility factors that are statistically correlated with increased risk of development of the relevant disease, disorder, and/or condition.

[0107] Three dimensional representation: As used herein, the term " three dimensional representation" refers to converting the lists of structure coordinates into structural models or graphical representation in three-dimensional space. In some embodiments, the three

dimensional structure may be displayed or used to performing computer modeling or fitting operations. In some embodiments, the structure coordinates themselves, without the displayed model, may be used to perform computer-based modeling and fitting operations. [0108] Unsaturated: As used herein, the term "unsaturated" means that a moiety has one or more units of unsaturation.

[0109] As used herein, the term "pharmaceutically acceptable salt" refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge et al., describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of this invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, nontoxic acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid or malonic acid or by using other methods used in the art such as ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like.

[0110] Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and

salts. Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, loweralkyl sulfonate and aryl sulfonate. [0111] In certain embodiments, neutral forms of the compounds are regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner. In some embodiments, the parent form of the compound differs from the various salt forms in certain physical properties, such as solubility in polar solvents.

[0112] The symbol "^w ", except when used as a bond to depict unknown or mixed stereochemistry, denotes the point of attachment of a chemical moiety to the remainder of a molecule or chemical formula.

Detailed Description of Certain Embodiments

STING

[0113] The protein TMEM173/STING (stimulator of interferon genes) (Ishikawa and

Barber, 2008; Zhong et al. 2008; Sun et al. 2009; Burdette et al. 2011; Ishikawa et al, 2009; Jin et al., 2008) is a central player in the innate immune response to nucleic acids, particularly cytosolic dsDNA (reviewed in Burdette and Vance, 2013; Cai et al., 2014; Danilchanka and Mekalanos, 2013; O'Neill, 2013; Paludan and Bowie, 2013; Xiao and Fitzgerald, 2013). STING responds to various pathogens, as well as to mitochondrial damage, and its overactivation may contribute or possibly even trigger the onset of autoimmune disorders such as systemic lupus erythematosus (Gall et al. 2012; Gehrke et al., 2013). STING's role in the immune system is consistent with its higher expression in certain organs such as the thymus, spleen and placenta. STING is also expressed in THP1 human monocytic cells.

[0114] An initial screen designed to discover potential regulators of the type I interferon

(IFN) antiviral response identified cyclic GMP-AMP (cGAMP) synthase (MB21Dl/cGAS) as a gene with broad antiviral effect (Schoggins et al. 2011). Independently, biochemical fractionation identified cGAS as the metazoan cytosolic DNA sensor and synthase of cGAMP, the endogenous second messenger that activates the type I IFN pathway (Sun et al. 2013; Wu et al. 2013). A structure-function study demonstrated that only one specific isomer of cGAMP, namely c[G(2',5')pA(3',5')p] was produced by cGAS (Gao et al. 2013). This isomer of the second messenger contained an unanticipated 2', 5 '-linkage at the GpA step, a feature subsequently validated by several independent studies (Diner et al. 2013; Ablasser et al. 2013; Zhang et al. 2013). Structures of dsDNA-bound cGAS with ATP and GTP (Gao et al. 2013; Civril et al. 2013), pppGpA dinucleotide intermediate (Gao et al. 2013), and the product c[G(2',5')pA(3',5')p] (Gao et al. 2013), along with biochemical analysis of reaction

intermediates, provided insights into the stepwise conversion of GTP and ATP in the first step to pppGpA (Gao et al. 2013; Ablasser et al. 2013) and subsequent cyclization to

c[G(2',5')pA(3',5')p] (Gao et al. 2013; Ablasser et al. 2013).

[0115] The identification of c[G(2',5')pA(3',5')p] as a novel second messenger generated by dsDNA-bound cGAS in the presence of GTP and ATP (Gao et al, 2013) has prompted studies of the role of c[G(2',5')pA(3',5')p] in activating the IFN pathway via the downstream receptor STING (Diner et al. 2013; Ablasser et al. 2013; Zhang et al. 2013). Binding of c[G(2',5')pA(3',5')p] to STING activates a cascade of events whereby STING recruits and activates ΙκΒ kinase (IKK) and TANK-binding kinase (TBK1), which following their phosphorylation, respectively activate nuclear transcription factor κΒ (NF-κΒ) and interferon regulatory factor 3 (IRF3). These activated proteins translocate to the nucleus to induce transcription of the genes encoding type I IFN and cytokines for promoting intercellular host immune defense (reviewed in Keating et al. 2011; Paludan and Bowie, 2013). STING is a direct sensor of bacterial cyclic dinucleotides (CDNs) such as c[di-GMP] (Burdette et al, 2011), although it was subsequently demonstrated that the host-encoded cytosolic DNA-binding sensor cyclic GMP-AMP synthase (cGAS) (Sun et al, 2013) and its product cyclic GMP-AMP

(cGAMP) (Wu et al, 2013) acted as the second messenger binding to STING in response to cells exposed to DNA.

[0116] In the human population, there are several STING variants, which may influence the responsiveness to cGAMP, its linkage isomers and other CDNs (Diner et al, 2013; Yi et al, 2013). Among them, R71/G230/R232/R293 (referred to as hSTING^R232) appears to be the most common variant (Yi et al, 2013). Thus, unless specified otherwise, the experiments described in the ensuing exemplification were based on this variant.

[0117] Human (h) and mouse (m) STING exhibit 68% amino acid identity and 81% similarity, with distinct sequence alleles reported in humans (Diner et al. 2013). Established numbering systems of human and mouse STING are offset by one residue, with hSTING and mSTING^R231 occupying corresponding positions. The amino acid sequences of hSTING

(accession no. NP 938023.1; SEQ ID NO.: 1) and mSTING (accession no.; SEQ ID NO.: 2) are shown in Table A.

Table A. Human and Mouse Stimulator of Interferon Genes Protein

[0119] hSTING is composed of a N-terminal transmembrane domain (aa 1-154), a central globular domain (aa 155-341) and a C-terminal tail (aa 342-379). Distinct sequence variants of either mouse or human STING have been studied with different functional assays and outcomes, complicating interpretation. Diner et al (2013) identified natural variant alleles of STING, namely the R232H variant to the genome reference of human STING (hSTING^H232, reference sequence) and the R231 A variant of mouse Sting (mSTING^A231), which were activated by c[G(2',5')pA(3',5')p] but not by c[di-GMP] or c[G(3',5')pA(3',5')p]. By contrast, Zhang et al (2013) proposed based on structural, calorimetric-based binding and cellular assays that c[G(2',5')pA(3',5')p] is the highest affinity ligand for hSTING^R232, even though their in vitro calorimetric binding measurements did not support their results seen with IFN induction cellular assays. Ablasser et al (2013) investigated the contribution of 2',5'- and 3 ',5 '-linkages in cGAMP and concluded that c[G(2',5')pA(3',5')p] was more potent than c[G(3',5')pA(3',5')] in activating hSTING from human fibroblasts and THP1 cells, and wild-type mSTING^R231.

[0120] Structural studies have been reported on hSTING^H232 in the free and c[di-GMP] bound states. STING forms a symmetrical dimer in both states with c[di-GMP] bound in a pocket within the dimer interface and anchored by a network of intermolecular hydrogen bonds (reviewed in Burdette and Vance, 2013). For all but one of the c[di-GMP]-hSTING^H232 complexes, the STING dimer adopts the same V-shaped conformation independent of the presence of the ligand and also does not completely surround the bound ligand. In the one

A230/R232

exception, c[di-GMP] -bound hSTING forms an anti-parallel β-pleated sheet cap over the binding pocket on complex formation and this conformational change further sequesters the bound ligand (Huang et al. 2012). More recently, the same conformational transition has been reported on formation of the complex between mSTING^R231 and the anti-viral drug CMA (Caviar et al. 2013) and on formation of the complex between hSTING^R232 and c[G(2',5')pA(3',5')p] (Zhang et al. 2013).

[0121] The present disclosure provides valuable insights into the structural basis and functional output of ligand-binding by hSTING and mSTING. Given STING's central role in immunoregulation of the anti-viral response and in eliciting a macrophage-dependent tumoricidal program (Kim et al. 2013), such insights permit design, production, and or characterization of useful STING modulators. In some embodiments, such modulators are useful in medicine (e.g., in therapy and/or in prophylaxis) of one or more diseases, disorders, or conditions.

[0122] The present disclosure provides insights relevant to selectivity of hSTING^R232 for

[G(2',5')pA(3',5')p], as well as its ability to recognize, bind to and/or discriminate between its linkage isomers.

[0123] The present disclosure also assesses the extent to which distinct STING alleles

H232 A231

(e.g., hSTING and mSTING ) and/or variants differentially respond to particular modulator agents.

[0124] Among other things, the present disclosure provides crystal structures of various

STING alleles and/or variants alone or complexed with one or more modulator or candidate modulator agents. Such crystal structures are useful, for example, to guide design of modulator agents, including modulator agents whose structures include moieties that can and/or do make specified interactions with complementary STING moieties. In some embodiments, such complementary STING moieties are present in some STING alleles or variants but not others. The present disclosure, therefore, among other things, provides technologies for designing, identifying and/or characterizing STING modulators that discriminate between or among STING alleles and/or variants.

STING Function

[0125] It is generally believed that STING coordinates multiple immune responses to infection, including the induction of interferons and STAT6-dependent response and selective autophagy response. STING plays an important role in innate immunity and mediates type I interferon production in response to intracellular DNA and a variety of intracellular pathogens, such as viruses, mycobacteria and intracellular parasites. For example, STING binds directly to cyclic di-GMP, and this recognition leads to the production of cytokines, such as type I interferon. Type I interferon protects infected cells and nearby cells from local infection in an autocrine and paracrine manner.

[0126] For example, binding of c[G(2',5')pA(3',5')p] to STING activates a cascade of events whereby STING recruits and activates ΙκΒ kinase (IKK) and TANK-binding kinase (TBKl), which following their phosphorylation, respectively activate nuclear transcription factor KB (NF-KB) and interferon regulatory factor 3 (IRF3). These activated proteins translocate to the nucleus to induce transcription of the genes encoding type I IFN and cytokines for promoting intercellular host immune defense (reviewed in Keating et al. 2011; Paludan and Bowie, 2013).

[0127] STING plays an important role in antiviral immunity and elicits powerful type I interferon immunity against viral infection. After viral entry, viral nucleic acids will be present in the cytosol of infected cells. Several DNA sensors, such as DAI, RNA polymerase III, IFI16, DDX41 and cGAS, can detect foreign nucleic acids. After recognizing viral DNA, DNA sensors initiate the downstream signaling pathways by activating STING-mediated interferon response. Viruses that activate a STING-depenent innate immune response include, but are not limited to, adenovirus, herpes simplex virus (e.g., HSV-1 and HSV-2), negative-stranded RNA virus- vesicular stomatitis virus (VSV), and combinations thereof.

[0128] A variety of assays are known to one of skill in the art that detect and/or characterize STING activities. In some embodiments, STING activity is or comprises interacting with a particular binding partner or partners. In some embodiments, STING activity is or comprises discriminating between potential partners. In some embodiments, STING activity is or comprises hSTING activity. In some embodiments, STING activity is or comprises mSTING activity.

[0129] In some embodiments, STING activity is or comprises phosphorylation of a particular substrate or substrates. In some embodiments, STING activity is or comprises phosphorylation of TBK1, IKK, IRF3, STAT6 and/or combinations thereof.

[0130] In some embodiments, STING activity is or comprises upregulation of gene expression of of IFN-β, CCL2, CCL20, and/or combinations thereof.

[0131] In some embodiments, a STING polypeptide shares at least one of these activites with a reference STING polypeptide, such as a wild type STING. In some embodiments, a STING polypeptide is considered to "share" an activity with a reference if it shows an acivity that would be recognized by those skilled in the art as comparable to, or not significiantly different from, that of a relevant reference in an appropriate assay that detects and/or

characterizes the activity. While the kinase activity of a STING polypeptide compared to a reference may be significantly lower, it can be recognized by its ability to phosphorylate STING- specific sites in bona- fide STING substrates such as IKK and TBK1.

STING Crystal Structure

[0132] Among other things, the present invention provides a crystalline (i.e., containing at least one crystal) or crystallizable composition comprising a STING polypeptide. In some embodiments, such a provided composition consists of or consists essentially of the STING polypeptide. In some embodiments, a composition is considered to "consist of a STING polypeptide if it includes only the polypeptide, one or more solvents, and optionally salts and/or metals. In some embodiments, such a provided composition includes one or more other agents such as one or more other polypeptides (e.g., one or more potential or actual STING binding partner polypeptides) and/or one or more interacting agents (e.g., small molecules).

[0133] In some embodiments, such a provided composition comprises a wild-type

STING polypeptide. Exemplary wild-type STING polypeptides include, but are not limited to, hSTING (SEQ ID NO: 1) and mSTING (SEQ ID NO: 2). In some embodiments, such a provided composition comprises a STING polypeptide comprising an N-terminal truncation. In some embodiments, a STING polypeptide comprises an N-terminal truncation of hSTING comprising a truncation of amino acid residues 1-139 (hSTING^140"379). In some embodiments, a STING polypeptide comprises an N-terminal truncation of mSTING comprising a truncation of amino acid residues 1-138 (mSTING^139-378).

[0134] In some embodiments, a STING polypeptide comprises a C-terminal truncation.

[0135] In some embodiments, a STING polypeptide comprises both an N-terminal truncation and a C-terminal truncation. In some embodiments, a STING polypeptide comprises both an N-terminal truncation and a C-terminal truncation of hSTING comprising a trunctation of N-terminal residues 1-154 and C-terminal residues 342-379 (hSTING^H232 comprising residues 155-341). In some embodiments, a STING polypeptide comprises both an N-terminal truncation and a C-terminal truncation of mSTING comprising a trunctation of N-terminal residues 1-153 and C-terminal residues 341-378 (mSTING^R231 comprising residues 154-340).

[0136] In some embodiments, a STING polypeptide comprises both an N-terminal truncation and one or more internal deletions. In some embodiments, a STING polypeptide comprises an N-terminal truncation, a C-terminal truncation, one or more internal deletions, and/or combinations thereof.

[0137] Without wishing to be bound by any particular theory, truncation and/or internal deletion of the STING polypeptide favors crystallization because it can reduce flexibility, can result in more compact shape, and eliminate undesirable events like aggregation, if for example, the deleted region has a hydrophobic binding site for a protein-binding partner.

[0138] In some embodiments, provided compositions comprise a STING polypeptide bound to one or more binding partners. In some embodiments, such a provided composition comprises a STING polypeptide bound to c[G(2',5')pA(3',5')p] (see, e.g., Table 1 : c[G(2',5')pA(3',5')p]-hSTING^H232 complex (4LOH) coordinates; and Table 3:

c[G(2',5')pA(3',5')p]-mSting^R231 complex (4LOJ) coordinates).

[0139] In some embodiments, such a provided composition comprises a STING polypeptide bound to c[G(2',5')pA(2',5')p] (see, e.g., Table 2: c[G(2',5')pA(2',5')p]- hSTING^H232 complex (4LOI) coordinates).

[0140] In some embodiments, such a provided composition comprises a STING polypeptide bound to c[G(3',5')pA(3',5')p] (see, e.g., Table 4: c[G(3',5')pA(3',5')p]-mSting^R231 complex (4LOK) coordinates).

[0141] In some embodiments, such a provided composition comprises a STING polypeptide bound to DMXAA (see, e.g., Table 5: DMXAA-mSting^R231 complex (4LOL) coordinates).

[0142] In some embodiments, such a provided composition comprises a STING polypeptide bound to DMXAA (see, e.g., Table 6: DMXAA-hSting^group2 complex (4QXO) coordinates).

[0143] In some embodiments, such a provided composition comprises a STING polypeptide bound to DMXAA (see, e.g., Table 7: DMXAA-hSTING⁰²³⁰¹ complex (4QXP) coordinates).

[0144] In some embodiments, such a provided composition comprises a STING polypeptide bound to DMXAA (see, e.g., Table 8: DMXAA-hSTING^sl62A/Q2661 complex (4QXQ) coordinates).

[0145] In some embodiments, such a provided composition comprises a STING polypeptide bound to DMXAA (see, e.g., Table 9: DMXAA-hSTING^{sl62A/G230I/Q2661} complex (4QXR) coordinates).

[0146] In some embodiments, provided composition comprise an STING polypeptide bound to one or more STING modulators. In some embodiments, provided composition comprises a STING polypeptide bound to one or more exemplary STING modulators including, but not limited to, analogs of of c[G(2',5')pA(3',5')p], DMXAA, CMA, and/or combinations thereof.

[0147] The present invention also provides structural information and/or analyses of

STING polypeptide crystals and/or sets thereof. In some embodiments, such structural information includes, but is not limited to, diffraction patterns, and/or coordinates, as well as any data sets, images, models, and/or graphical representations thereof or generated therefrom. In some embodiments, such graphical representations may include, for example, space-filling models, molecular surface representations, shell or boundary models, ribbon models, stick models; and/or combinations thereof.

[0148] In some embodiments, provided information is or comprises differences observed between or among structures that differ from one another in the presence or absence of one or more binding partners and/or interacting agents. In some embodiments, provided information is or comprises differences observed between or among structures that differ from one another in the presence or absence of one or more binding partners and/or one or more modulators.

[0149] In some embodiments, such structural information and/or analyses may be embodied in a tangible medium (e.g., a computer-readable medium) or a storage environment. Thus, the present invention provides tangible embodiments of STING polypeptide crystal structure information, as well as its use, for example, by or with a computer system, in any of a variety of applications. For example, in some embodiments, such structural information and/or analyses may be accessed by, transported to or from, and/or otherwise utilized by a computer system or program running thereon.

STING Modulators

[0150] As discussed herein, among other things, the present disclosure defines and/or provides certain STING modulators. In some embodiments, the present disclosure provides technologies for identifying, designing, and/or characterizing STING modulators. In some embodiments, STING modulators are specific STING modulators. In some embodiments, STING modulators are specific modulators of one or more STING alleles or variants; in some such embodiments, STING modulators have differential effects on different STING alleles or variants and/or discriminate between or among such alleles or variants.

[0151] In some embodiments, the present disclosure provides STING modulators that are

DMXAA analogs. DMXAA (5,6-dimethylxanthenone-4-acetic acid, Vadimezan) was initially identified as a small molecule exhibiting immune modulatory activities through induction of cytokines, and disrupting tumor vascularization in mouse xenotransplantation models (Baguley and Ching, 2002). The induction of interferon (IFN) β expression by DMXAA also slowed the growth of tumors in vivo (Head and Jameson, 2010; Roberts et al, 2008). DMXAA, in combination with paclitaxel and carboplatin showed promising efficacy, and was therefore evaluated in a phase II clinical trial against non-small-cell lung cancer, but subsequently failed in human phase III trials (Lara et al. 2011). Recently, it has been demonstrated that DMXAA- induced IFN production by murine macrophages was impaired by the absence of STING

(Prantner et al. 2012), suggesting that DMXAA targets the STING pathway. Despite high sequence identity between mSting and hSTING, DMXAA, which only activates mSting and has no effect on hSTING (Conlon et al. 2013; Kim et al, 2013), which presumably hampered further therapeutic development of DMXAA as a human drug.

[0152] In some embodiments, DMXAA analogs include substitutions at position 1 and/or position 2 (Fig. 5A). In some embodiments, the H at position 1 and/or 2 is replaced by an OH or O-methyl group. In some embodiments, positions 1 and/or 2 could also be replaced by F, CI, N0₂ groups to facilitate hydrogen bond formation with Serl62 of hSTING. Without wishing to be bound to a particular theory, hydrogen replacement by either an OH or O-methyl group facilitates hydrogen bond formation with Serl62 of hSTING.

[0153] In some embodiments, DMXAA analogs include substitutions at position 7 and/or position 8 (Fig. 5A). In some embodiments, the H at position 7 and/or 8 is replaced by methyl and/or larger alkyl groups. Without wishing to be bound to a particular theory, hydrogen replacement by methyl and/or larger alkyl groups facilitates hydrophobic contacts with He 165 of hSTING. In some embodiments, the H at position 7 is replaced by polar groups (OH, OCH₃, F, CI, NO₂). Without wishing to be bound to a particular theory, hydrogen replacement by polar groups facilitates hydrogen bond formation with Gln266 of hSTING. [0154] The present disclosure describes systematic structure-function studies of mouse and human STING interaction with DMXAA. The present disclosure specifically defines interaction points between STING modulator compounds and STING moieties. In one example, the present disclosure specifically defines interaction points between DMXAA moieties and STING moieties. Moreover, the present disclosure describes modifications of hSTING and/or DMXAA structure (i.e., mutations of hSTING and analogs of DMXAA) that permit interaction between them. Thus, the present disclosure defines DMXAA analogs that can act as hSTING modulators, including as specific hSTING modulators (even relative to mSting).

[0155] The present disclosure also describes cyclic dinucleotide compounds (e.g., cGAMP-analogs and/or isomers) active as STING modulators, and particularly as hSTING modulators (e.g., specific hSTING modulators). Among other things, the present disclosure demonstrates that hSTING was more discriminating towards 2 ',5 '-linkage-containing isomers versus those isomers containing all 3 ',5 '-linkages.

[0156] The present disclosure also describes 10-carboxymethyl-9-acridine (CMA) analogs that are active as STING modulators, and particularly as hSTING modulators (e.g., specific hSTING modulators). In certain embodiments, alternative CMA analogs are provided and tested for STING modulatory activity as described herein.

[0157] In some embodiments, provided STING modulators are compounds whose structure include one or more moieties that interact with a residue corresponding to Serl62 and/or He 165 of hSTING. In some embodiments, provided STING modulators are compounds whose structure include one or more moieties that interact with a residue corresponding to Gly230, Gln266, Serl62, and/or Ilel65 of hSTING. In some embodiments, provided STING modulators are compounds whose structure include one or more moieties that interact with a residue corresponding to Gly230, Gln266, and/or Serl62 of hSTING. In some embodiments, provided STING modulators are compounds whose structures include one or more moieties that interact with a residue corresponding to Leul70, Ile235, Ilel65, Thr267, Arg238, Tyr240, and/or Thr263 of hSTING. In some embodiments, provided STING modulators are compounds whose structures include one or more moieties that interact with a residue corresponding to Gly230, Gln266, Serl62, Ilel65, Leul70, Ile235, Ilel65, Thr267, Arg238, Tyr240, and/or Thr263 of hSTING.

[0158] In some embodiments, provided STING modulators are characterized by variety well understood and known by those skilled in the art including, but not limited to cGAMP stimulation of cells, ELISA, Isothermal Titration Calorimetry (ITC) Binding Assay, and/or combinations thereof. For example, in some embodiments, provided STING modulators show activity in an ITC binding assay such as is described in the Examples.

[0159] In some embodiments, in accordance with the present invention, STING modulators, and particularly hSTING modulators (e.g., specific hSTING modulators) are useful as agonists or antagonists of innate immunity. In some embodiments, in accordance with the present invention, STING modulators, and particularly hSTING modulators (e.g., specific hSTING modulators) are useful as anti-cancer agents. In some embodiments, in accordance with the present invention, STING modulators, and particularly hSTING modulators (e.g., specific hSTING modulators) are useful in vaccine development. In some embodiments, in accordance with the present invention, STING modulators, and particularly hSTING modulators (e.g., specific hSTING modulators) are useful as therapies for autoimmune disorders.

[0160] In some embodiments, a STING modulator is a compound described in

International Patent Application No. PCT/US 14/35909, the entire contents of which is hereby incorporated by reference.

STING Species Selectivity

[0161] In one aspect, the present invention defines the molecular basis underlying

DMXAA species selectivity. The small molecule drug DMXAA specifically activates the STING nucleic acid-sensing pathway in a species-dependent manner. Functional and structural studies demonstrate that DMXAA activates mouse but not human STING (Conlon et al., 2013; Kim et al., 2013). DMXAA showed great promise in mouse cancer models, underscoring its potential for human application, notwithstanding the outcome of a phase III clinical trial for non- small cell lung carcinoma (Lara et al., 2011). Hence it is important to recognize that while DMXAA itself is apparently not a viable drug, pharmacological modulation of STING remains an ideal therapeutic strategy.

[0162] One model recently suggested that DMXAA species-selectivity might be due to non-conserved residues within mSTING that could directly bind to DMXAA (Conlon et al., 2013). However, previous structural studies established that DMXAA binds to mSTING within the same pocket as cGAMP and that DMXAA binding involves interactions with identical amino acids in both mSTING and hSTING (Gao et al., 2013b). Therefore, although the non-conserved residues do not participate in direct interaction with DMXAA, they potentially play alternative roles in DMXAA recognition. Results disclosed herein on ITC binding (Figures 15B, 15C and 20A) and IFN induction (Figure 15D) studies established that the non-conserved residues located within the lid region of the ligand-binding pocket (group2) are important for the species-specific response to DMXAA. Furthermore, the structural studies described herein reveal the same 'closed' conformation for the complexes of DMXAA bound to hSTING^group2 (Figure 15E) and mSTING (Figure 20B), confirming the important role of group2 residues in DMXAA

recognition and complex formation.

[0163] Moreover, the present disclosure identifies a hydrophobic interaction between the substituted 1230 and the residues from both the lid region and other parts of the protein in the hSTING^group2-DMXAA complex (Figure 15G), a distinctive feature that was also found in the structure of the mSTING-DMXAA complex (Figure 20C). All residues that form the

hydrophobic pocket that contains 1230 are conserved in both human and mouse STING proteins. The gain of function of hSTING⁰²³⁰¹ and inversely the loss of function of mSTING^I229G or mSTING^I229A in their abilities to induce IFN gene expression in response to DMXAA, further confirmed the role of this residue in species-specific recognition of DMXAA (Figure 16A, B). A crystal structure of the hSTING^G230I-DMXAA complex also exhibited the active 'closed' conformation (Figures 16C, D), further supporting the conclusion that this single point substitution outside of the binding pocket of hSTING modulates sensitivity to the otherwise mouse-selective DMXAA ligand. Hydrophobic interactions could help facilitate formation of the lid region and other parts of the protein, allowing mSTING to form the 'closed' conformation more readily than hSTING in response to DMXAA. [0164] The disclosed structural studies indicate that mSTING is induced more readily to assume the 'closed' conformation than hSTING in response to CDNs and their analogs. Due to this 'intrinsic disadvantage' of hSTING, better fitting DMXAA analogs need to be designed to allow hSTING to overcome the energy barrier of transitioning from an Open' to a 'closed' state. To enable the rational design of suitable DMXAA modifications, the ensuing Examples systematically introduced hSTING substitutions within the binding pocket and tested their influence on DMXAA-induced IFN-β production. Following this strategy and guided by co- crystal structures of STING substituents with DMXAA, the present invention identifies two point substitutions within the ligand-binding pocket, S162A reported previously (Gao et al, 2013b) and Q266I, each of which strongly promote DMXAA recognition (Figure 17A). These data suggest that modestly-altered DMXAA derivatives might be sufficient to bind and activate hSTING. By introducing the above substitutions into the predominant hSTING alleles, a dose- dependent response to DMXAA is restored in all cases (Figures 22 A, B). However, the Q293- carrying hSTING variants still responded poorly to DMXAA (Figure 17E), in line with previous reports showing an impaired CDN response by hSTING^Q293 and hSTING^HAQ (Jin et al, 2011; Yi et al., 2013). This general effect of Q293 will most likely also affect the responsiveness to human-active DMXAA derivatives, suggesting a need for STING-genotyping in patients and possible adjustment of drug dosing in future studies.

[0165] The S 162A/G230I/Q266I triple substitution of hSTING showed an order of magnitude higher activity than mSTING (Figure 18B), indicating that all three substitutions confer a substantial synergistic effect to DMXAA recognition. hSTING^{sl62A/G230I/Q2661} might therefore be used as a benchmark hSTING synthetic allele in future drug development studies using humanized mouse models. In addition to the luciferase reporter assays in human 293T cells, the ensuing Examples describe IFN and proinflammatory cytokine/chemokine production for hSTING substitutions in BMDCs from the STING^Gt/Gt mouse and similar results (Figure 18F and 22E).

[0166] The ensuing Examples also show DMXAA-induced type I IFN and

proinflammatory cytokine/chemokine production in STING-deficient bone marrow-derived dendritic cells (BMDCs) reconstituted with the hSTING mutants by retroviral transduction. In some embodiments, reconstitution with hSTING^{sl62A/G230I/Q2661} resulted in the highest responsiveness to DMXAA stimulation in primary DCs with the induction of IFNB, IL-6, CCL5 and CXCL10 gene expression. These findings provide a guide for future rational drug design of DMXAA variants with potential IFN-P-stimulating activity in humans that are needed for the development of anti-cancer therapies and vaccine adjuvants

[0167] Thus the present invention provides, among other things, a comprehensive structural, biophysical, and functional analysis of DMXAA association with select substitutions within hSTING. The present invention highlights the role of the lid residue at position 230 (229 in mSTING) and unveils the structural basis for the mSTING-selectivity of DMXAA. Provided structural and functional results also shed light on strategies to restore an efficient DMXAA- response of hSTING based on the binding pocket S162A and Q266I substitutions. Imitating the effects of these amino acid substitutions by rational design of reciprocal DMXAA derivatives should lead to the development of human-active STING agonists for anti-tumor, anti-viral, and vaccine adjuvant applications. The same principles may apply to generation of analogs of CMA, the other small molecule that to date can target mSTING but not hSTING (Caviar et al., 2013).

Structure-Based Drug Design

[0168] In some embodiments, the present disclosure provides systems for identifying and/or characterizing STING modulators. In some embodiments, the present disclosure provides a method of designing, identifying and/or characterizing a STING modulator comprising the steps of: a) providing an image of a STING crystal that includes at least one potential interaction site; b) docking in the image at least one moiety that is a potential STING modulator structural element; and c) assessing one or more features of a potential moiety-interaction site interaction.

[0169] In some embodiments, the at least one potential interaction site includes a site selected from the group consisting of Serl62, Ilel65, and combinations thereof. In some embodiments, the at least one potential interaction site includes a site selected from the group consisting of Serl62, Ilel65, Gly230, Gln266, and combinations thereof. In some

embodiments, the at least one potential interaction site includes Serl62. In some embodiments, the at least one potential interaction site includes He 165. In some embodiments, the at least one potential interaction site includes Gly230. In some embodiments, the at least one potential interaction site includes Gln266. In some embodiments, the modulator is a compound disclosed herein.

[0170] In some embodiments, the one or more features include at least one feature selected from the group consisting of: spatial separation between the moiety and the potential interaction site; energy of the potential moiety-interaction site interaction, and/or combinations thereof.

[0171] In some embodiments, a method further comprises a step of providing an image of a potential STING modulator comprising the moiety docked with the image of the STING crystal. In some embodiments, a method further comprises a step of comparing the image with that of a STING crystal including a bound known modulator, substrate, or product.

Computer Systems

[0172] As will be appreciated by those skilled in the art, reading the present disclosure, in some aspects, the present invention is ideally suited for use in computer-implemented inventions. FIG. 24 shows but one example of a computing device 2500 and a mobile computing device 2550 that can be used to implement certain techniques described in this disclosure. The computing device 2500 depicted in FIG. 24 is intended to represent any of a variety forms of digital computers, such as laptops, desktops, workstations, personal digital assistants, servers, blade servers, mainframes, and other appropriate computers. The depicted mobile computing device 2550 is intended to represent any appropriate form of mobile devices, such as personal digital assistants, cellular telephones, smart-phones, tablet computers, and other similar computing devices. Moreover, the components shown in FIG. 24 and elsewhere in the Figures, their connections and relationships, and their functions, are meant to be examples only, and are not meant to be limiting.

[0173] The computing device depicted in FIG. 24 2500 includes a processor 2502, a memory 2504, a storage device 2506, a high-speed interface 2508 connecting to the memory 2504 and multiple high-speed expansion ports 2510, and a low-speed interface 2512 connecting to a low-speed expansion port 2514 and the storage device 2506. Each of the processor 2502, the memory 2504, the storage device 2506, the high-speed interface 2508, the high-speed expansion ports 2510, and the low-speed interface 2512, are interconnected using various busses, and may be mounted on a common motherboard or in other manners as appropriate. The processor 2502 can process instructions for execution within the computing device 2500, including instructions stored in the memory 2504 or on the storage device 2506 to display graphical information for a GUI on an external input/output device, such as a display 2516 coupled to the high-speed interface 2508. In some implementations, multiple processors and/or multiple buses may be used, as appropriate, along with multiple memories and types of memory. Also, multiple computing devices may be connected, with each device providing portions of the necessary operations (e.g., as a server bank, a group of blade servers, or a multi-processor system).

[0174] The memory 2504 depicted in FIG. 24 stores information within the computing device 2500. In some implementations, the memory 2504 is a volatile memory unit or units. In some implementations, the memory 2504 is a non-volatile memory unit or units. The memory 2504 may also be another form of computer-readable medium, such as a magnetic or optical disk.

[0175] The storage device 2506 depicted in FIG. 24 is capable of providing mass storage for the computing device 2500. In some implementations, the storage device 2506 may be or contain a computer-readable medium, such as a floppy disk device, a hard disk device, an optical disk device, or a tape device, a flash memory or other similar solid state memory device, or an array of devices, including devices in a storage area network or other configurations.

Instructions can be stored in an information carrier. The instructions, when executed by one or more processing devices (for example, processor 2502), perform one or more methods, such as those described above. The instructions can also be stored by one or more storage devices such as computer- or machine-readable mediums (for example, the memory 2504, the storage device 2506, or memory on the processor 2502).

[0176] The high-speed interface 2508 manages bandwidth-intensive operations for the computing device 2500, while the low-speed interface 2512 manages lower bandwidth-intensive operations. Such allocation of functions is an example only. In some implementations, the highspeed interface 2508 is coupled to the memory 2504, the display 2516 (e.g., through a graphics processor or accelerator), and to the high-speed expansion ports 2510, which may accept various expansion cards (not shown). In the implementation, the low-speed interface 2512 is coupled to the storage device 2506 and the low-speed expansion port 2514. The low-speed expansion port 2514, which may include various communication ports (e.g., USB, Bluetooth®, Ethernet, wireless Ethernet) may be coupled to one or more input/output devices, such as a keyboard, a pointing device, a scanner, or a networking device such as a switch or router, e.g., through a network adapter.

[0177] The computing device 2500 may be implemented in a number of different forms, as shown in the figure. For example, it may be implemented as a standard server 2520, or multiple times in a group of such servers. In addition, it may be implemented in a personal computer such as a laptop computer 2522. It may also be implemented as part of a rack server system 2524. Alternatively, components from the computing device 2500 may be combined with other components in a mobile device (not shown), such as a mobile computing device 2550. Each of such devices may contain one or more of the computing device 2500 and the mobile computing device 2550, and an entire system may be made up of multiple computing devices communicating with each other.

[0178] The mobile computing device 2550 depicted in FIG. 24 includes a processor

2552, a memory 2564, an input/output device such as a display 2554, a communication interface 2566, and a transceiver 2568, among other components. The mobile computing device 2550 may also be provided with a storage device, such as a micro-drive or other device, to provide additional storage. Each of the processor 2552, the memory 2564, the display 2554, the communication interface 2566, and the transceiver 2568, are interconnected using various buses, and several of the components may be mounted on a common motherboard or in other manners as appropriate.

[0179] The processor 2552 depicted in FIG. 24 can execute instructions within the mobile computing device 2550, including instructions stored in the memory 2564. The processor 2552 may be implemented as a chipset of chips that include separate and multiple analog and digital processors. The processor 2552 may provide, for example, for coordination of the other components of the mobile computing device 2550, such as control of user interfaces, applications run by the mobile computing device 2550, and wireless communication by the mobile computing device 2550.

[0180] The processor 2552 may communicate with a user through a control interface

2558 and a display interface 2556 coupled to the display 2554. The display 2554 depicted in FIG. 24 may be, for example, a TFT (Thin-Film-Transistor Liquid Crystal Display) display or an OLED (Organic Light Emitting Diode) display, or other appropriate display technology. The display interface 2556 may comprise appropriate circuitry for driving the display 2554 to present graphical and other information to a user. The control interface 2558 may receive commands from a user and convert them for submission to the processor 2552. In addition, an external interface 2562 may provide communication with the processor 2552, so as to enable near area communication of the mobile computing device 2550 with other devices. The external interface 2562 may provide, for example, for wired communication in some implementations, or for wireless communication in other implementations, and multiple interfaces may also be used.

[0181] The memory 2564 depicted in FIG. 24 stores information within the mobile computing device 2550. The memory 2564 can be implemented as one or more of a computer- readable medium or media, a volatile memory unit or units, or a non-volatile memory unit or units. An expansion memory 2574 may also be provided and connected to the mobile computing device 2550 through an expansion interface 2572, which may include, for example, a SIMM (Single In Line Memory Module) card interface. The expansion memory 2574 may provide extra storage space for the mobile computing device 2550, or may also store applications or other information for the mobile computing device 2550. Specifically, the expansion memory 2574 may include instructions to carry out or supplement the processes described above, and may include secure information also. Thus, for example, the expansion memory 2574 may be provide as a security module for the mobile computing device 2550, and may be programmed with instructions that permit secure use of the mobile computing device 2550. In addition, secure applications may be provided via the SIMM cards, along with additional information, such as placing identifying information on the SIMM card in a non-hackable manner.

[0182] The memory may include, for example, flash memory and/or NVRAM memory

(non-volatile random access memory), as discussed below. In some implementations, instructions are stored in an information carrier, that the instructions, when executed by one or more processing devices (for example, processor 2552), perform one or more methods, such as those described above. The instructions can also be stored by one or more storage devices, such as one or more computer- or machine-readable mediums (for example, the memory 2564, the expansion memory 2574, or memory on the processor 2552). In some implementations, the instructions can be received in a propagated signal, for example, over the transceiver 2568 or the external interface 2562.

[0183] The mobile computing device 2550 depicted in FIG. 24 may communicate wirelessly through the communication interface 2566, which may include digital signal processing circuitry where necessary. The communication interface 2566 may provide for communications under various modes or protocols, such as GSM voice calls (Global System for Mobile communications), SMS (Short Message Service), EMS (Enhanced Messaging Service), or MMS messaging (Multimedia Messaging Service), CDMA (code division multiple access), TDMA (time division multiple access), PDC (Personal Digital Cellular), WCDMA (Wideband Code Division Multiple Access), CDMA2000, or GPRS (General Packet Radio Service), among others. Such communication may occur, for example, through the transceiver 2568 using a radio-frequency. In addition, short-range communication may occur, such as using a

Bluetooth®, Wi-Fi™, or other such transceiver (not shown). In addition, a GPS (Global Positioning System) receiver module 2570 may provide additional navigation- and location- related wireless data to the mobile computing device 2550, which may be used as appropriate by applications running on the mobile computing device 2550.

[0184] The mobile computing device 2550 depicted in FIG. 24 may also communicate audibly using an audio codec 2560, which may receive spoken information from a user and convert it to usable digital information. The audio codec 2560 may likewise generate audible sound for a user, such as through a speaker, e.g., in a handset of the mobile computing device 2550. Such sound may include sound from voice telephone calls, may include recorded sound (e.g., voice messages, music files, etc.) and may also include sound generated by applications operating on the mobile computing device 2550. [0185] The mobile computing device 2550 may be implemented in a number of different forms, as shown in FIG. 24. For example, it may be implemented as a cellular telephone 2580. It may also be implemented as part of a smart-phone 2582, personal digital assistant, or other similar mobile device.

[0186] Various implementations of the systems and techniques described here can be realized in digital electronic circuitry, integrated circuitry, specially designed ASICs (application specific integrated circuits), computer hardware, firmware, software, and/or combinations thereof. These various implementations can include implementation in one or more computer programs that are executable and/or interpretable on a programmable system including at least one programmable processor, which may be special or general purpose, coupled to receive data and instructions from, and to transmit data and instructions to, a storage system, at least one input device, and at least one output device.

[0187] These computer programs (also known as programs, software, software applications or code) include machine instructions for a programmable processor, and can be implemented in a high-level procedural and/or object-oriented programming language, and/or in assembly/machine language. As used herein, the terms machine-readable medium and computer-readable medium refer to any computer program product, apparatus and/or device (e.g., magnetic discs, optical disks, memory, Programmable Logic Devices (PLDs)) used to provide machine instructions and/or data to a programmable processor, including a machine- readable medium that receives machine instructions as a machine -readable signal. The term machine-readable signal refers to any signal used to provide machine instructions and/or data to a programmable processor.

[0188] To provide for interaction with a user, the systems and techniques described here can be implemented on a computer having a display device (e.g., a CRT (cathode ray tube) or LCD (liquid crystal display) monitor) for displaying information to the user and a keyboard and a pointing device (e.g., a mouse or a trackball) by which the user can provide input to the computer. Other kinds of devices can be used to provide for interaction with a user as well; for example, feedback provided to the user can be any form of sensory feedback (e.g., visual feedback, auditory feedback, or tactile feedback); and input from the user can be received in any form, including acoustic, speech, or tactile input.

[0189] The systems and techniques described here can be implemented in a computing system that includes a back end component (e.g., as a data server), or that includes a middleware component (e.g., an application server), or that includes a front end component (e.g., a client computer having a graphical user interface or a Web browser through which a user can interact with an implementation of the systems and techniques described here), or any combination of such back end, middleware, or front end components. The components of the system can be interconnected by any form or medium of digital data communication (e.g., a communication network). Examples of communication networks include a local area network (LAN), a wide area network (WAN), and the Internet.

[0190] The computing system can include clients and servers. A client and server are generally remote from each other and typically interact through a communication network. The relationship of client and server arises by virtue of computer programs running on the respective computers and having a client-server relationship to each other.

[0191] In some embodiments, there is provided an implementation of an exemplary cloud computing environment for subscription management in a multi-channel context aware communication environment. As shown in FIG. 23, the cloud computing environment 2400 may include one or more resource providers 2402a, 2402b, 2402c (collectively, 2402). Each resource provider 2402 may include computing resources. In some implementations, computing resources may include any hardware and/or software used to process data. For example, computing resources may include hardware and/or software capable of executing algorithms, computer programs, and/or computer applications. In some implementations, exemplary computing resources may include application servers and/or databases with storage and retrieval capabilities. Each resource provider 2402 may be connected to any other resource provider 2402 in the cloud computing environment 2400. In some implementations, the resource providers 2402 may be connected over a computer network 2408. Each resource provider 2402 may be connected to one or more computing device 2404a, 2404b, 2404c (collectively, 2404), over the computer network 2408. [0192] The cloud computing environment 2400 depicted in FIG. 23 may include a resource manager 2406. The resource manager 2406 may be connected to the resource providers 2402 and the computing devices 2404 over the computer network 2408. In some

implementations, the resource manager 2406 may facilitate the provision of computing resources by one or more resource providers 2402 to one or more computing devices 2404. The resource manager 2406 may receive a request for a computing resource from a particular computing device 2404. The resource manager 2406 may identify one or more resource providers 2402 capable of providing the computing resource requested by the computing device 2404. The resource manager 2406 may select a resource provider 2402 to provide the computing resource. The resource manager 2406 may facilitate a connection between the resource provider 2402 and a particular computing device 2404. In some implementations, the resource manager 2406 may establish a connection between a particular resource provider 2402 and a particular computing device 2404. In some implementations, the resource manager 2406 may redirect a particular computing device 2404 to a particular resource provider 2402 with the requested computing resource.

[0193] As will be appreciated by those skilled in the art, reading the present disclosure in some embodiments, the present invention provides a computer system comprising one or more of (a) atomic coordinate data as disclosed herein [+/- a root mean square deviation from the Ca atoms of note more than 1.5A (or 1.0 A or 0.5 A)]; (b) structure factor data (where a structure factor comprises the amplitude and phase of the diffracted wave) for STING, said structure factor data being derivable from the atomic coordinate data of Tables 1-5 +/- a root mean square deviation from the Ca atoms of note more than 1.5 A (or 1.0 A or 0.5 A); (c) atomic coordinate data of a STING modulator protein generated by homology modeling of the target based on the data disclosed herein +/- a root mean square deviation from the Ca atoms of not more than 1.5A (or 1.0 A or 0.5 A); (d) atomic coordinate data of a STING modulator protein generated by interpreting X-ray crystallographic data or NMR data by reference to the data disclosed herein +/- a root mean square deviation from the Ca atoms of note more than 1.5A (or 1.0 A or 0.5 A); or (e) structure factor data a derivable from the atomic coordinate data of (c) or (d). In certain embodiments, a computer system comprises: a computer-readable data storage medium comprising data storage material encoded with the computer-readable data; (a) a working memory for storing instructions for processing said computer-readable data; and (b) a central- processing unit coupled to said working memory and to said computer-readable data storage medium for processing said computer-readable data and thereby generating structures, characterizing structures and/or performing rational drug design.

[0194] In some embodiments, there is provided a machine-readable data storage medium, comprising a data storage material encoded with machine-readable data, wherein said data comprises all or part of a c[G(2',5')pA(3',5')p]-hSTING^H232 complex defined by structure coordinates of hSTING^H232amino acids (SEQ ID NO.: l), according Table 1; or a molecule or molecular complex comprising all or part of a c[G(2',5')pA(3',5')p]-hSTING^H232 complex defined by structure coordinates of corresponding amino acids that are identical to said hSTING^H232 amino acids, wherein the root mean square deviation of the backbone atoms between said corresponding amino acids and said hSTING^H232 amino acids is not more than about 3.0A, 2.5 A, 2.0 A, 1.5 A, 1.0 A; or a molecule or molecular complex comprising all or part of a c[G(2',5')pA(3',5')p]-hSTING^H232 complex defined by structure coordinates of a set of corresponding amino acids, wherein the root mean square deviation of the backbone atoms between said set of corresponding amino acids and said hSTING^H232 amino acids is not more than about 1.1, 0.9, 0.7, or 0.5 A, and wherein at least one of said corresponding amino acids is not identical to the hSTING^H232 amino acid to which it corresponds.

[0195] In some embodiments, there is provided a machine-readable data storage medium, comprising a data storage material encoded with machine-readable data, wherein said data comprises all or part of a c[G(2',5')pA(2',5')p]-hSTING^H232 complex defined by structure coordinates of hSTING^H232 amino acids (SEQ ID NO.: l), according Table 2; or a molecule or molecular complex comprising all or part of a c[G(2',5')pA(2',5')p]-hSTING^H232 complex defined by structure coordinates of corresponding amino acids that are identical to said hSTING^H232 amino acids, wherein the root mean square deviation of the backbone atoms between said corresponding amino acids and said hSTING^H232 amino acids is not more than about 3.0A, 2.5 A, 2.0 A, 1.5 A, 1.0 A; or a molecule or molecular complex comprising all or part of a c[G(2',5')pA(2',5')p]-hSTING^H232 complex defined by structure coordinates of a set of corresponding amino acids, wherein the root mean square deviation of the backbone atoms between said set of corresponding amino acids and said hSTING amino acids is not more than about 1.1, 0.9, 0.7, or 0.5 A, and wherein at least one of said corresponding amino acids is not identical to the hSTING^H232 amino acid to which it corresponds.

[0196] In some embodiments, there is provided a machine-readable data storage medium, comprising a data storage material encoded with machine-readable data, wherein said data comprises all or part of a c[G(2',5')pA(3',5')p]-mSting^R231 complex defined by structure coordinates of mSting^R231 amino acids (SEQ ID NO.:2), according Table 3; or a molecule or molecular complex comprising all or part of a c[G(2',5')pA(3',5 ')p]-mSting^R231 complex defined by structure coordinates of corresponding amino acids that are identical to said mSting^R231 amino acids, wherein the root mean square deviation of the backbone atoms between said

corresponding amino acids and said mSting^R231 amino acids is not more than about 3.0 A, 2.5 A, 2.0 A, 1.5 A, 1.0 A; or a molecule or molecular complex comprising all or part of a

c[G(2',5')pA(3',5')p]-mSting^R231 complex defined by structure coordinates of a set of corresponding amino acids, wherein the root mean square deviation of the backbone atoms between said set of corresponding amino acids and said mSting^R231 amino acids is not more than about 1.1, 0.9, 0.7, or 0.5 A, and wherein at least one of said corresponding amino acids is not identical to the mSting^R231 amino acid to which it corresponds.

[0197] In some embodiments, there is provided a machine-readable data storage medium, comprising a data storage material encoded with machine-readable data, wherein said data comprises all or part of a c[G(3',5')pA(3',5')p]-mSting^R231 complex defined by structure coordinates of mSting^R231 amino acids (SEQ ID NO.:2), according Table 4; or a molecule or molecular complex comprising all or part of a c[G(3',5')pA(3',5 ')p]-mSting^R231 complex defined by structure coordinates of corresponding amino acids that are identical to said mSting^R231 amino acids, wherein the root mean square deviation of the backbone atoms between said

corresponding amino acids and said mSting^R231 amino acids is not more than about 3.0 A, 2.5 A, 2.0 A, 1.5 A, 1.0 A; or a molecule or molecular complex comprising all or part of a

c[G(2',5')pA(3',5')p]-mSting^R231 complex defined by structure coordinates of a set of corresponding amino acids, wherein the root mean square deviation of the backbone atoms between said set of corresponding amino acids and said mSting^R231 amino acids is not more than about 1.1, 0.9, 0.7, or 0.5 A, and wherein at least one of said corresponding amino acids is not identical to the mSting^R231 amino acid to which it corresponds.

[0198] In some embodiments, there is provided a machine-readable data storage medium, comprising a data storage material encoded with machine-readable data, wherein said data comprises all or part of a DMXAA-mSting^R231 complex defined by structure coordinates of mSting^R231 amino acids (SEQ ID NO.:2), according Table 5; or a molecule or molecular complex comprising all or part of a DMXAA-mSting^R231 complex defined by structure coordinates of corresponding amino acids that are identical to said mSting^R231 amino acids, wherein the root mean square deviation of the backbone atoms between said corresponding amino acids and said mSting^R231 amino acids is not more than about 3.0A, 2.5 A, 2.0 A, 1.5 A, 1.0 A; or a molecule or molecular complex comprising all or part of a DMXAA-mSting^R231 complex defined by structure coordinates of a set of corresponding amino acids, wherein the root mean square deviation of the backbone atoms between said set of corresponding amino acids and said mSting^R231 amino acids is not more than about 1.1, 0.9, 0.7, or 0.5 A, and wherein at least one of said corresponding amino acids is not identical to the mSting^R231 amino acid to which it corresponds.

[0199] In some embodiments, there is provided a machine-readable data storage medium, comprising a data storage material encoded with machine-readable data, wherein said data comprises all or part of a DMXAA-hSTING^group2 complex defined by structure coordinates of hSTING^group2 amino acids, according Table 6; or a molecule or molecular complex comprising all or part of a DMXAA-hSTING^group2 complex defined by structure coordinates of

corresponding amino acids that are identical to said hSTING^group2 amino acids, wherein the root mean square deviation of the backbone atoms between said corresponding amino acids and said hSTING^group2 amino acids is not more than about 3.0A, 2.5 A, 2.0 A, 1.5 A, 1.0 A; or a molecule or molecular complex comprising all or part of a DMXAA-hSTING^group2 complex defined by structure coordinates of a set of corresponding amino acids, wherein the root mean square deviation of the backbone atoms between said set of corresponding amino acids and said hSTING^group2 amino acids is not more than about 1.1, 0.9, 0.7, or 0.5 A, and wherein at least one of said corresponding amino acids is not identical to the hSTING^group2 amino acid to which it corresponds. [0200] In some embodiments, there is provided a machine-readable data storage medium, comprising a data storage material encoded with machine-readable data, wherein said data comprises all or part of a DMXAA-hSTING⁰²³⁰¹ complex defined by structure coordinates of hSTING⁰²³⁰¹ amino acids, according Table 7; or a molecule or molecular complex comprising all or part of a DMXAA-hSTING⁰²³⁰¹ complex defined by structure coordinates of corresponding amino acids that are identical to said hSTING⁰²³⁰¹ amino acids, wherein the root mean square deviation of the backbone atoms between said corresponding amino acids and said hSTING⁰²³⁰¹ amino acids is not more than about 3.0A, 2.5 A, 2.0 A, 1.5 A, 1.0 A; or a molecule or molecular complex comprising all or part of a DMXAA-hSTING⁰²³⁰¹ complex defined by structure coordinates of a set of corresponding amino acids, wherein the root mean square deviation of the backbone atoms between said set of corresponding amino acids and said hSTING⁰²³⁰¹ amino acids is not more than about 1.1, 0.9, 0.7, or 0.5 A, and wherein at least one of said

corresponding amino acids is not identical to the hSTING⁰²³⁰¹ amino acid to which it

corresponds.

[0201] In some embodiments, there is provided a machine-readable data storage medium, comprising a data storage material encoded with machine-readable data, wherein said data comprises all or part of a DMXAA-hSTING^sl62A/(^²⁶⁶¹ complex defined by structure coordinates of hSTING^sl62A/Q2661 amino acids, according Table 8; or a molecule or molecular complex comprising all or part of a DMXAA-hSTING^sl62A/(^²⁶⁶¹ complex defined by structure coordinates of corresponding amino acids that are identical to said hSTING^sl62A/(^²⁶⁶¹ amino acids, wherein the root mean square deviation of the backbone atoms between said corresponding amino acids and said _hSTING^sl62A/Q2661 amino acids is not more than about 3.0A, 2.5 A, 2.0 A, 1.5 A, 1.0 A; or a molecule or molecular complex comprising all or part of a DMXAA-hSTING^sl62A/(^²⁶⁶¹ complex defined by structure coordinates of a set of corresponding amino acids, wherein the root mean square deviation of the backbone atoms between said set of corresponding amino acids and said hSTING^sl62A/Q2661 amino acids is not more than about 1.1, 0.9, 0.7, or 0.5 A, and wherein at least one of said corresponding amino acids is not identical to the STING^{sl62A Q2661} amino acid to which it corresponds. [0202] In some embodiments, there is provided a machine-readable data storage medium, comprising a data storage material encoded with machine-readable data, wherein said data comprises all or part of a DMXAA-hSTING^{sl62A/G230I/Q2661} complex defined by structure coordinates of STING^{sl62A G230I/Q2661 /Q2661} amino acids, according Table 9; or a molecule or molecular complex comprising all or part of a DMXAA-hSTING^{sl62A/G230I/Q2661} complex defined by structure coordinates of corresponding amino acids that are identical to said

hSTING^{sl62A/G230I/(}^²⁶⁶¹ amino acids, wherein the root mean square deviation of the backbone atoms between said corresponding amino acids and said _hSTING^{sl62A/G230I/Q2661} amino acids is not more than about 3.0A, 2.5 A, 2.0 A, 1.5 A, 1.0 A; or a molecule or molecular complex comprising all or part of a DMXAA-hSTING^{sl62A/G230I/Q2661} complex defined by structure coordinates of a set of corresponding amino acids, wherein the root mean square deviation of the backbone atoms between said set of corresponding amino acids and said _hSTING^{sl62A/G230I/Q2661} amino acids is not more than about 1.1, 0.9, 0.7, or 0.5 A, and wherein at least one of said corresponding amino acids is not identical to the hSTING^{sl62A G230I/}^²⁶⁶¹ amino acid to which it corresponds.

[0203] In some embodiments, the data storage material is encoded with machine- readable data comprising all or part of a superposition of a STING complex with one or more additional molecules and/or complexes. In some embodiments, data storage material is encoded with machine-readable data comprising all or part of a superposition of a STING protein and STING modulator complex. In some embodiments, one or more domain(s) of STING are superposed with one or more molecules and/or complexes. In some embodiments, the cyclic dinucleotide cleft domain of STING and DMXAA are superpositioned. In some embodiments, the cyclic dinucleotide cleft domain of STING and a candidate STING modulator are

superpositioned.

[0204] In some embodiments, the present invention provides a computer system comprising executable code for computer-aided and/or structure-based drug design of STING modulators. In some embodiments, the present invention provides a computer system

comprising executable code for docking STING modulators in at least one potential STING interaction site (e.g., dinucleotide cleft domain, ligand-binding pocket). In some embodiments, said executable code comprises instructions for providing an image of a STRING crystal that includes at least one potential interaction site; docking in the image at least one moiety that is a potential STING modulator structural element; and assessing one or more features of a potential moiety-interaction site interaction.

[0205] In some embodiments, said executable code comprises a determining step, wherein said determining step comprises a prediction of 1.) whether said moiety will bind to at least one potential STING interaction site; 2.) calculates the strength of binding affinity; and 3.) calculates moiety specificity. In some embodiments, the determining step further comprises predicting the conformation of the moiety when bound to at least one potential interaction site. In some embodiments, the determining step further comprises one or more predictions of conformational changes in a STING polypeptide when said moiety binds at least one potential interaction site.

[0206] In some embodiments, provided computer system comprise executable code for superimposing all or part of a STING crystal or crystallizable composition with another crystal or crystallizable composition.

[0207] In some embodiments, provided computer systems comprise executable code for modeling interactions with a STING crystal or crystallizable composition.

Identifying, Designing and/or Characterizing STING modulators

[0208] As described herein, the present disclosure describes systems useful in the identification, design, and/or characterization of STING modulators and/or STING modulator candidates. In some embodiments, such systems are or comprise structure based drug design systems. In some embodiments, such systems are or comprise one or more activity assays.

[0209] In some embodiments, candidate STING modulator compounds are tested in accordance with systems described herein in order to identify and/or characterize those with desirable structural and/or functional attributes. In some embodiments, a population of candidate STING modulator compounds is provided through structure-based drug design predictions of interacting moieties. In some embodiments, a population of candidate STING modulator compounds is or comprises analogs of a reference compound selected from the group consisting of cyclic dinucleotides, DMXAA, CMA, and combinations thereof.

Pharmaceutical Compositions

[0210] The pharmaceutical compositions can be in a variety of forms including oral dosage forms, topic creams, topical patches, iontophoresis forms, suppository, nasal spray and inhaler, eye drops, intraocular injection forms, depot forms, as well as injectable and infusible solutions. Methods for preparing pharmaceutical composition are well known in the art.

[0211] Pharmaceutical compositions typically contain the active agent described herein

(e.g. STING modulators) in an amount effective to achieve the desired therapeutic effect while avoiding or minimizing adverse side effects. Pharmaceutically acceptable preparations and salts of the active agent are provided herein and are well known in the art. For the administration of STING modulators and the like, the amount administered desirably is chosen that is

therapeutically effective with few to no adverse side effects. The amount of the therapeutic or pharmaceutical composition which is effective in the treatment of a particular disease, disorder or condition depends on the nature and severity of the disease, the target site of action, the subject's weight, special diets being followed by the subject, concurrent medications being used, the administration route and other factors that are recognized by those skilled in the art. The dosage can be adapted by the clinician in accordance with conventional factors such as the extent of the disease and different parameters from the subject. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems (e.g., as described by the U.S. Department of Health and Human Services, Food and Drug Administration, and Center for Drug Evaluation and Research in "Guidance for Industry: Estimating Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers",

Pharmacology and Toxicology, July 2005, the entire contents of which are incorporated herein by reference).

[0212] Various delivery systems are known and can be used to administer active agent described herein (e.g. STING modulators) or a pharmaceutical composition comprising the same. The pharmaceutical compositions described herein can be administered by any suitable route including, intravenous or intramuscular injection, intraventricular or intrathecal injection (for central nervous system administration), orally, topically, subcutaneously, intrapulmonary (e.g., inhalation), subconjunctivally, intraocularly, or via intranasal, intradermal, sublingual, vaginal, rectal or epidural routes.

[0213] Other delivery systems well known in the art can be used for delivery of the pharmaceutical compositions described herein, for example via aqueous solutions, encapsulation in microparticules, or microcapsules. The pharmaceutical compositions of the present invention can also be delivered in a controlled release system. For example, a polymeric material can be used (see, e.g., Smolen and Ball, Controlled Drug Bioavailability, Drug product design and performance, 1984, John Wiley & Sons; Ranade and Hollinger, Drug Delivery Systems, pharmacology and toxicology series, 2003, 2^nd edition, CRRC Press). Alternatively, a pump may be used (Saudek et al, N. Engl. J. Med. 321 :574 (1989)). The compositions described herein may also be coupled to a class of biodegradable polymers useful in achieving controlled release of the drug, for example, polylactic acid, polyorthoesters, cross-linked amphipathic block copolymers and hydrogels, polyhydroxy butyric acid, and polydihydropyrans.

[0214] As described above, pharmaceutical compositions desirably include a

pharmaceutically acceptable carrier. The term carrier refers to diluents, adjuvants, excipients or vehicles with which STING modulators are administered. Such pharmaceutical carriers include sterile liquids such as water and oils including mineral oil, vegetable oil (e.g., soybean oil or corn oil), animal oil or oil of synthetic origin. Aqueous glycerol and dextrose solutions as well as saline solutions may also be employed as liquid carriers of the pharmaceutical compositions of the present invention. The choice of the carrier depends on factors well recognized in the art, such as the nature of the peptide, peptide derivative or peptidomimetic, its solubility and other physiological properties as well as the target site of delivery and application. Examples of suitable pharmaceutical carriers are described in Remington: The Science and Practice of Pharmacy by Alfonso R. Gennaro, 2003, 21^th edition, Mack Publishing Company. Moreover, suitable carriers for oral administration are known in the art and are described, for example, in U.S. Patent Nos. 6,086,918, 6,673,574, 6,960,355, and 7,351,741 and in WO2007/131286, the disclosures of which are hereby incorporated by reference. [0215] Further pharmaceutically suitable materials that may be incorporated in pharmaceutical preparations include absorption enhancers including those intended to increase paracellular absorption, pH regulators and buffers, osmolarity adjusters, preservatives, stabilizers, antioxidants, surfactants, thickeners, emollient, dispersing agents, flavoring agents, coloring agents, and wetting agents.

[0216] Examples of suitable pharmaceutical excipients include, water, glucose, sucrose, lactose, glycol, ethanol, glycerol monostearate, gelatin, starch flour (e.g., rice flour), chalk, sodium stearate, malt, sodium chloride, and the like. The pharmaceutical compositions comprising STING modulators can take the form of solutions, capsules, tablets, creams, gels, powders sustained release formulations and the like. The composition can be formulated as a suppository, with traditional binders and carriers such as triglycerides (see Remington: The Science and Practice of Pharmacy by Alfonso R. Gennaro, 2003, 21^th edition, Mack Publishing Company). Such compositions contain a therapeutically effective amount of the therapeutic composition, together with a suitable amount of carrier so as to provide the form for proper administration to the subject. The formulations are designed to suit the mode of administration and the target site of action (e.g., a particular organ or cell type).

[0217] The pharmaceutical compositions comprising the active agent described herein

(e.g. STING modulators) also include compositions formulated as neutral or salt forms.

Pharmaceutically acceptable salts include those that form with free amino groups and those that react with free carboxyl groups. Non-toxic alkali metal, alkaline earth metal, and ammonium salts commonly used in the pharmaceutical industry include sodium, potassium, lithium, calcium, magnesium, barium, ammonium, and protamine zinc salts, which are prepared by methods well known in the art. Also included are non-toxic acid addition salts, which are generally prepared by reacting the compounds of the present invention with suitable organic or inorganic acid. Representative salts include the hydrobromide, hydrochloride, valerate, oxalate, oleate, laureate, borate, benzoate, sulfate, bisulfate, acetate, phosphate, tysolate, citrate, maleate, fumarate, tartrate, succinate, napsylate salts, and the like.

[0218] Examples of fillers or binders that may be used in accordance with the present invention include acacia, alginic acid, calcium phosphate (dibasic), carboxymethylcellulose, carboxymethylcellulose sodium, hydroxyethylcellulose, hydroxypropylcellulose,

hydroxypropylmethylcellulose, dextrin, dextrates, sucrose, tylose, pregelatinized starch, calcium sulfate, amylose, glycine, bentonite, maltose, sorbitol, ethylcellulose, disodium hydrogen phosphate, disodium phosphate, disodium pyrosulfite, polyvinyl alcohol, gelatin, glucose, guar gum, liquid glucose, compressible sugar, magnesium aluminum silicate, maltodextrin, polyethylene oxide, polymethacrylates, povidone, sodium alginate, tragacanth microcrystalline cellulose, starch, and zein. In certain embodiments, a filler or binder is microcrystalline cellulose.

[0219] Examples of disintegrating agents that may be used include alginic acid, carboxymethylcellulose, carboxymethylcellulose sodium, hydroxypropylcellulose (low substituted), microcrystalline cellulose, powdered cellulose, colloidal silicon dioxide, sodium croscarmellose, crospovidone, methylcellulose, polacrilin potassium, povidone, sodium alginate, sodium starch glycolate, starch, disodium disulfite, disodium edathamil, disodium edetate, disodiumethylenediaminetetraacetate (EDTA) crosslinked polyvinylpyrrolidones, pregelatinized starch, carboxymethyl starch, sodium carboxymethyl starch, microcrystalline cellulose.

[0220] Examples of lubricants include calcium stearate, canola oil, glyceryl

palmitostearate, hydrogenated vegetable oil (type I), magnesium oxide, magnesium stearate, mineral oil, poloxamer, polyethylene glycol, sodium lauryl sulfate, sodium stearate fumarate, stearic acid, talc and, zinc stearate, glyceryl behapate, magnesium lauryl sulfate, boric acid, sodium benzoate, sodium acetate, sodium benzoate/sodium acetate (in combination), DL-leucine.

[0221] Examples of silica flow conditioners include colloidal silicon dioxide, magnesium aluminum silicate and guar gum. Another most preferred silica flow conditioner consists of silicon dioxide.

[0222] Examples of stabilizing agents include acacia, albumin, polyvinyl alcohol, alginic acid, bentonite, dicalcium phosphate, carboxymethylcellulose, hydroxypropylcellulose, colloidal silicon dioxide, cyclodextrins, glyceryl monostearate, hydroxypropyl methylcellulose, magnesium trisilicate, magnesium aluminum silicate, propylene glycol, propylene glycol alginate, sodium alginate, carnauba wax, xanthan gum, starch, stearate(s), stearic acid, stearic monoglyceride and stearyl alcohol. [0223] In some embodiments, the present invention contemplates oral formulations containing the active agent described herein (e.g. STING modulators). For example,

pharmaceutical compositions described herein may include a cyclodextrin or cyclodextrin derivative. Cyclodextrins are generally made up of five or more a-D-glycopyranoside unites linked l->4. Typically, cyclodextrins contain a number of glucose monomers ranging from six to eight units in a ring, creating a cone shape (a-cyclodextrin: six membered sugar ring molecule, β-cyclodextrin: seven sugar ring molecule, γ-cyclodextrin: eight sugar ring molecule).

Exemplary cyclodextrins and cyclodextrin derivatives are disclosed in U.S. Patent No.

7,723,304, U.S. Publication No. 2010/0196452, and U.S. Publication No. 2010/0144624, the entire contents of each of which are incorporated herein by reference. For example, in some embodiments, a cyclodextrin in accordance with the present invention is an alkylated

cyclodextrin, hydroxyalkylated cyclodextrin, or acylated cyclodextrin. In some embodiments, a cyclodextrin is a hydroxypropyl β-cyclodextrin. Exemplary cyclodextrin derivatives are disclosed in Szejtli, J. Chem Rev, (1998), 98, 1743-1753; and Szente, L and Szejtli, J., Advance Drug Delivery Reviews, 36 (1999) 17-28, the entire contents of each of which are hereby incorporated by reference. Examples of cyclodextin derivatives include methylated

cyclodextrins (e.g., RAMEB; randomly methylated β-cyclodextrin); hydroxyalkylated cyclodextrins (hydroxypropyl-P-cyclodextrin and hydroxypropyl γ-cyclodextrin); acetylated cyclodextrins (acetyl-y-cyclodextrin); reactive cyclodextrins (chlorotriazinyl β- cyclodextrin); and branched cyclodextrins (glucosyl- and maltosyl β-cyclodextrin); acetyl-y-cyclodextrin;

acetyl^-cyclodextrin, sulfobutyl-β cyclodextrin, sulfated α-, β- and γ-cyclodextrins;

sulfoalkylated cyclodextrins; and hydroxypropyl β-cyclodextrin.

Dosing

[0224] Typically, active agent described herein (e.g. STING modulators) in an amount ranging from 0.001 to 100 mg/kg/day is administered to the subject. For example, in some embodiments, about 0.01 mg/kg/day to about 25 mg/kg/day, about 1 mg/kg/day to about 20 mg/kg/day, 0.2 mg/kg/day to about 10 mg/kg/day, about 0.02 mg/kg/day to about 0.1 mg/kg/day, or about 1 mg/kg/day to about 100 mg/kg/day is administered to the subject. In some

embodiments, active agent described herein (e.g. STING modulators) in an amount of about 10 μΒ/kg/day, 50 μΒ/kg/day, 100 μΒ/kg/day, 200 μΒ/kg/day, 300 μΒ/kg/day, 400 μΒ/kg/day, 500 μg/kg/day, 600 μg/kg/day, 700 μg/kg/day, 800 μg/kg/day, 900 μg/kg/day, or 1000 μg/kg/day is administered to the subject.

[0225] In some embodiments, the STING modulator is administered at an effective dose ranging from about 1-1,000 μg/kg/day (e.g., ranging from about 1-900 μg/kg/day, 1-800 μg/kg/day, 1-700 μg/kg/day, 1-600 μg/kg/day, 1-500 μg/kg/day, 1-400 μg/kg/day, 1-300 μg/kg/day, 1-200 μg/kg/day, 1-100 μg/kg/day, 1-90 μg/kg/day, 1-80 μg/kg/day, 1-70 μg/kg/day, 1-60 μg/kg/day, 1-50 μg/kg/day, 1-40 μg/kg/day, 1-30 μg/kg/day, 1-20 μg/kg/day, 1-10 μg/kg/day). In some embodiments, the STING modulator is administered at an effective dose ranging from about 1-500 μg/kg/day. In some embodiments, the STING modulator is administered at an effective dose ranging from about 1-100 μg/kg/day. In some embodiments, the STING modulator is administered at an effective dose ranging from about 1-60 μg/kg/day. In some embodiments, the STING modulator is administered at an effective dose selected from about 1, 2, 4, 6, 8, 10, 15, 20, 25, 30, 35, 40, 45, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1,000 ug/kg/day.

[0226] In some embodiments, a therapeutically effective amount of an STING modulator may be an amount ranging from about 10-1,000 mg (e.g., about 20 mg - 1,000 mg, 30 mg - 1,000 mg, 40 mg - 1,000 mg, 50 mg - 1,000 mg, 60 mg - 1,000 mg, 70 mg - 1,000 mg, 80 mg - 1,000 mg, 90 mg - 1,000 mg, about 10-900 mg, 10-800 mg, 10-700 mg, 10-600 mg, 10-500 mg, 100-1000 mg, 100-900 mg, 100-800 mg, 100-700 mg, 100-600 mg, 100-500 mg, 100-400 mg, 100-300 mg, 200-1000 mg, 200-900 mg, 200-800 mg, 200-700 mg, 200-600 mg, 200-500 mg, 200-400 mg, 300-1000 mg, 300-900 mg, 300-800 mg, 300-700 mg, 300-600 mg, 300-500 mg, 400 mg - 1,000 mg, 500 mg - 1,000 mg, 100 mg - 900 mg, 200 mg - 800 mg, 300 mg - 700 mg, 400 mg - 700 mg, and 500 mg - 600 mg). In some embodiments, an STING modulator is present in an amount of or greater than about 10 mg, 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg. In some embodiments, an STING modulator is present in an amount of or less than about 1000 mg, 950 mg, 900 mg, 850 mg, 800 mg, 750 mg, 700 mg, 650 mg, 600 mg, 550 mg, 500 mg, 450 mg, 400 mg, 350 mg, 300 mg, 250 mg, 200 mg, 150 mg, or 100 mg. In some embodiments, the therapeutically effective amount described herein is provided in one dose. In some embodiments, the therapeutically effective amount described herein is provided in one day.

[0227] In other embodiments, a therapeutically effective amount may be, for example, about 0.001 mg/kg weight to 500 mg/kg weight, e.g., from about 0.001 mg/kg weight to 400 mg/kg weight, from about 0.001 mg/kg weight to 300 mg/kg weight, from about 0.001 mg/kg weight to 200 mg/kg weight, from about 0.001 mg/kg weight to 100 mg/kg weight, from about 0.001 mg/kg weight to 90 mg/kg weight, from about 0.001 mg/kg weight to 80 mg/kg weight, from about 0.001 mg/kg weight to 70 mg/kg weight, from about 0.001 mg/kg weight to 60 mg/kg weight, from about 0.001 mg/kg weight to 50 mg/kg weight, from about 0.001 mg/kg weight to 40 mg/kg weight, from about 0.001 mg/kg weight to 30 mg/kg weight, from about 0.001 mg/kg weight to 25 mg/kg weight, from about 0.001 mg/kg weight to 20 mg/kg weight, from about 0.001 mg/kg weight to 15 mg/kg weight, from about 0.001 mg/kg weight to 10 mg/kg weight. In some embodiments, the therapeutically effective amount described herein is provided in one dose. In some embodiments, the therapeutically effective amount described herein is provided in one day.

[0228] In still other embodiments, a therapeutically effective amount may be, for example, about 0.0001 mg/kg weight to 0.1 mg/kg weight, e.g. from about 0.0001 mg/kg weight to 0.09 mg/kg weight, from about 0.0001 mg/kg weight to 0.08 mg/kg weight, from about 0.0001 mg/kg weight to 0.07 mg/kg weight, from about 0.0001 mg/kg weight to 0.06 mg/kg weight, from about 0.0001 mg/kg weight to 0.05 mg/kg weight, from about 0.0001 mg/kg weight to about 0.04 mg/kg weight, from about 0.0001 mg/kg weight to 0.03 mg/kg weight, from about 0.0001 mg/kg weight to 0.02 mg/kg weight, from about 0.0001 mg/kg weight to 0.019 mg/kg weight, from about 0.0001 mg/kg weight to 0.018 mg/kg weight, from about 0.0001 mg/kg weight to 0.017 mg/kg weight, from about 0.0001 mg/kg weight to 0.016 mg/kg weight, from about 0.0001 mg/kg weight to 0.015 mg/kg weight, from about 0.0001 mg/kg weight to 0.014 mg/kg weight, from about 0.0001 mg/kg weight to 0.013 mg/kg weight, from about 0.0001 mg/kg weight to 0.012 mg/kg weight, from about 0.0001 mg/kg weight to 0.011 mg/kg weight, from about 0.0001 mg/kg weight to 0.01 mg/kg weight, from about 0.0001 mg/kg weight to 0.009 mg/kg weight, from about 0.0001 mg/kg weight to 0.008 mg/kg weight, from about 0.0001 mg/kg weight to 0.007 mg/kg weight, from about 0.0001 mg/kg weight to 0.006 mg/kg weight, from about 0.0001 mg/kg weight to 0.005 mg/kg weight, from about 0.0001 mg/kg weight to 0.004 mg/kg weight, from about 0.0001 mg/kg weight to 0.003 mg/kg weight, from about 0.0001 mg/kg weight to 0.002 mg/kg weight. In some embodiments, the therapeutically effective dose may be 0.0001 mg/kg weight, 0.0002 mg/kg weight, 0.0003 mg/kg weight, 0.0004 mg/kg weight, 0.0005 mg/kg weight, 0.0006 mg/kg weight, 0.0007 mg/kg weight, 0.0008 mg/kg weight, 0.0009 mg/kg weight, 0.001 mg/kg weight, 0.002 mg/kg weight, 0.003 mg/kg weight, 0.004 mg/kg weight, 0.005 mg/kg weight, 0.006 mg/kg weight, 0.007 mg/kg weight, 0.008 mg/kg weight, 0.009 mg/kg weight, 0.01 mg/kg weight, 0.02 mg/kg weight, 0.03 mg/kg weight, 0.04 mg/kg weight, 0.05 mg/kg weight, 0.06 mg/kg weight, 0.07 mg/kg weight, 0.08 mg/kg weight, 0.09 mg/kg weight, or 0.1 mg/kg weight. The effective dose for a particular individual can be varied (e.g., increased or decreased) over time, depending on the needs of the individual. In some embodiments, the therapeutically effective amount described herein is provided in one dose. In some embodiments, the therapeutically effective amount described herein is provided in one day.

[0229] In some embodiments, a provided composition is provided as a pharmaceutical formulation. In some embodiments, a pharmaceutical formulation is or comprises a unit dose amount for administration in accordance with a dosing regimen correlated with achievement of the reduced incidence or risk of cancer. In some embodiments, a pharmaceutical formulation is or comprises a unit dose amount for administration in accordance with a dosing regimen correlated with achievement of the reduced incidence or risk of infectious disease (i.e., vaccine). In some embodiments, a pharmaceutical formulation is or comprises a unit dose amount for administration in accordance with a dosing regimen correlated with achievement of the reduced incidence or risk of autoimmune disorders.

[0230] In some embodiments, a formulation comprising a STING modulator as described herein administered as a single dose. In some embodiments, a formulation comprising a STING modulator as described herein is administered at regular intervals. Administration at an

"interval," as used herein, indicates that the therapeutically effective amount is administered periodically (as distinguished from a one-time dose). The interval can be determined by standard clinical techniques. In some embodiments, a formulation comprising a STING modulator as described herein is administered bimonthly, monthly, twice monthly, triweekly, biweekly, weekly, twice weekly, thrice weekly, daily, twice daily, or every six hours. The administration interval for a single individual need not be a fixed interval, but can be varied over time, depending on the needs of the individual.

[0231] As used herein, the term "bimonthly" means administration once per two months

(i.e., once every two months); the term "monthly" means administration once per month; the term "triweekly" means administration once per three weeks (i.e., once every three weeks); the term "biweekly" means administration once per two weeks (i.e., once every two weeks); the term "weekly" means administration once per week; and the term "daily" means administration once per day.

[0232] In some embodiments, a formulation comprising a STING modulator as described herein is administered at regular intervals indefinitely. In some embodiments, a formulation comprising a STING modulator as described herein is administered at regular intervals for a defined period. In some embodiments, a formulation comprising a STING modulator as described herein is administered at regular intervals for 5 years, 4, years, 3, years, 2, years, 1 year, 11 months, 10 months, 9 months, 8 months, 7 months, 6 months, 5 months, 4 months, 3 months, 2 months, a month, 3 weeks, 2, weeks, a week, 6 days, 5 days, 4 days, 3 days, 2 days or a day.

Combination Therapy

[0233] In some embodiments, the present invention provides STING modulator agents for use in combination with one or more additional therapeutic and/or diagnostic agents and/or modalities. In some embodiments, provided agents are useful in combination with one or more other therapeutic agents or modalities known to be useful in the treatment or prevention of one or more STING -associated diseases, disorders, or conditions, and/or with the relief of one or more symptoms of such diseases, disorders, or conditions. For example, in some embodiments, provided agents are useful in combination with one or more chemotherapeutic, autoimmune medications and/or infectious disease agents. In some embodiments, provided agents are useful in combination with one or more other agents or modalities that is or are approved by the United States Food and Drug Administration or one or more other non-US agencies.

[0234] In some embodiments, agents utilized in combination may be included in a single pharmaceutical compositions. More commonly, however, agents utilized in combination are administered in accordance with overlapping regimens so that a subject is simultaneously exposed to both (or all) agents, and/or is exposed to individual agents in a predetermined order and/or with a predetermined timing.

[0235] For purposes of the present disclosure, the term "palliative" refers to treatment that is focused on the relief of symptoms of a disease and/or side effects of a therapeutic regimen, but is not curative. For example, in some embodiments, palliative treatment encompasses painkillers and antinausea medications. Alternatively or additionally, in some embodiments, chemotherapy, radiotherapy, and surgery can all be used palliatively (that is, to reduce symptoms without going for cure; e.g., for shrinking tumors and reducing pressure, bleeding, pain, and/or other symptoms or signs of cancer).

[0236] In some embodiments, a STING modulator is administered in combination with one or more known therapeutic agents (e.g., autoimmune medications) currently used for treatment of autoimmune disorders (e.g., systemic lupus erythematosus).

[0237] In some embodiments, a STING modulator is administered in combination with one or more known therapeutic agents (e.g., anti-viral medications) currently used for treatment of infectious disease (e.g., pathogenic infection).

[0238] In some embodiments, the known therapeutic agent(s) is/are administered according to its standard or approved dosing regimen and/or schedule. In some embodiments, the known therapeutic agent(s) is/are administered according to a regimen that is altered as compared with its standard or approved dosing regimen and/or schedule. In some embodiments, such an altered regimen differs from the standard or approved dosing regimen in that one or more unit doses is altered (e.g., reduced or increased) in amount, and/or in that dosing is altered in frequency (e.g., in that one or more intervals between unit doses is expanded, resulting in lower frequency, or is reduced, resulting in higher frequency). Applications for STING modulators

[0239] In certain embodiments provided modulators are useful in medicine. In some embodiments, provided modulators are useful in treating immune disease, disorders, or conditions. In some embodiments, the present invention provides a method for the treatment or prevention of an immune disease, disorder, or condition comprising administering to a subject in need thereof a provided modulator or a pharmaceutical composition thereof.

[0240] In some embodiments, the immune disease, disorder, or condition is an autoimmune disease, disorder, or condition. In certain embodiments, the immune disease, disorder, or condition is selected from the group consisting of any of a variety of diseases, disorders, and/or conditions, including but not limited to one or more of the following:

autoimmune disorders (e.g. diabetes, lupus, multiple sclerosis, psoriasis, rheumatoid arthritis); inflammatory disorders (e.g. arthritis, pelvic inflammatory disease); infectious diseases (e.g. viral infections (e.g., HIV, HCV, RSV), bacterial infections, fungal infections, sepsis); neurological disorders (e.g. Alzheimer's disease, Huntington's disease; autism; Duchenne muscular dystrophy); cardiovascular disorders (e.g. atherosclerosis, hypercholesterolemia, thrombosis, clotting disorders, angiogenic disorders such as macular degeneration); proliferative disorders (e.g. cancer, benign neoplasms); respiratory disorders (e.g. chronic obstructive pulmonary disease); digestive disorders (e.g. inflammatory bowel disease, ulcers); musculoskeletal disorders (e.g. fibromyalgia, arthritis); endocrine, metabolic, and nutritional disorders (e.g. diabetes, osteoporosis); urological disorders (e.g. renal disease); psychological disorders (e.g. depression, schizophrenia); skin disorders (e.g. wounds, eczema); blood and lymphatic disorders (e.g.

anemia, hemophilia); etc. In some embodiments, the immune disease, disorder, or condition is characterized by inflammation. In some embodiments, the immune disease, disorder, or condition is caused by, sustained by, or related to cGAS activation. In some embodiments, the immune disease, disorder, or condition is caused by, sustained by, or related to STING activation.

[0241] In some embodiments the autoimmune disorder or disease is selected from Acute disseminated encephalomyelitis (AD EM), Addison's disease, Agammaglobulinemia, Alopecia areata, Amyotrophic lateral sclerosis (Also Lou Gehrig's disease; Motor Neuron Disease), Ankylosing Spondylitis, Antiphospholipid syndrome, Antisynthetase syndrome, Atopic allergy, Atopic dermatitis, Autoimmune aplastic anemia, Autoimmune cardiomyopathy, Autoimmune enteropathy, Autoimmune hemolytic anemia, Autoimmune hepatitis, Autoimmune inner ear disease, Autoimmune lymphoproliferative syndrome, Autoimmune peripheral neuropathy, Autoimmune pancreatitis, Autoimmune polyendocrine syndrome, Autoimmune progesterone dermatitis, Autoimmune thrombocytopenic purpura, Autoimmune urticarial, Autoimmune uveitis, Balo disease/Balo concentric sclerosis, Beliefs disease, Berger's disease, Bickerstaf s encephalitis, Blau syndrome, Bullous pemphigoid Cancer, Castleman's disease, Celiac disease, Chagas disease, Chronic inflammatory demyelinating polyneuropathy, Chronic recurrent multifocal osteomyelitis, Chronic obstructive pulmonary disease, Churg-Strauss syndrome, Cicatricial pemphigoid Cogan syndrome, Cold agglutinin disease, Complement component 2 deficiency, Contact dermatitis, Cranial arteritis, CREST syndrome, Crohn's disease (idiopathic inflammatory bowel disease "IBD"), Cushing's Syndrome, Cutaneous leukocytoclastic angiitis, Dego's disease, Dermatitis herpetiformis, Dermatomyositis, Diabetes mellitus type 1, Diffuse cutaneous systemic sclerosis, Dressler's syndrome, Drug-induced lupus, Discoid lupus erythematosus, Eczema, Endometriosis, Enthesitis-related arthritis, Eosinophilic fasciitis, Eosinophilic gastroenteritis, Epidermolysis bullosa acquisita, Erythema nodosum,

Erythroblastosis fetalis, Essential mixed cryoglobulinemia, Evan's syndrome, Fibrodysplasia ossificans progressiva, Fibrosing alveolitis (or Idiopathic pulmonary fibrosis), Gastritis, Gastrointestinal pemphigoid, Glomerulonephritis, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome (GBS), Hashimoto's encephalopathy, Hashimoto's thyroiditis, Henoch- Schonlein purpura, Herpes gestationis aka Gestational Pemphigoid, Hidradenitis suppurativa, Hughes-Stovin syndrome, Hypogammaglobulinemia, Idiopathic inflammatory demyelinating diseases, Idiopathic pulmonary fibrosis, Idiopathic thrombocytopenic purpura, IgA nephropathy, Inclusion body myositis, Chronic inflammatory demyelinating polyneuropathy, Interstitial cystitis, Juvenile idiopathic arthritis aka Juvenile rheumatoid arthritis, Kawasaki's disease, Lambert-Eaton myasthenic syndrome, Leukocytoclastic vasculitis, Lichen planus, Lichen sclerosus, Linear IgA disease (LAD), Lupoid hepatitis aka Autoimmune hepatitis, Lupus erythematosus, Majeed syndrome, Meniere's disease, Microscopic polyangiitis, Miller-Fisher syndrome see Guillain-Barre Syndrome, Mixed connective tissue disease, Morphea, Mucha- Habermann disease aka Pityriasis lichenoides et varioliformis acuta, Multiple sclerosis,

Myasthenia gravis, Myositis, Narcolepsy, Neuromyelitis optica (also Devic's disease),

Neuromyotonia, Occular cicatricial pemphigoid, Opsoclonus myoclonus syndrome, Ord's thyroiditis, Palindromic rheumatism, PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcus), Paraneoplastic cerebellar degeneration, Paroxysmal nocturnal hemoglobinuria (PNH), Parry Romberg syndrome, Parsonage-Turner syndrome, Pars planitis, Pemphigus vulgaris, Pernicious anaemia, Perivenous encephalomyelitis, POEMS syndrome, Polyarteritis nodosa, Polymyalgia rheumatica, Polymyositis, Primary biliary cirrhosis, Primary sclerosing cholangitis, Progressive inflammatory neuropathy, Psoriasis, Psoriatic arthritis, Pyoderma gangrenosum, Pure red cell aplasia, Rasmussen's encephalitis, Raynaud phenomenon, Relapsing polychondritis, Reiter's syndrome, Restless leg syndrome,

Retroperitoneal fibrosis, Rheumatoid arthritis, Rheumatic fever, Sarcoidosis, Schizophrenia, Schmidt syndrome, Schnitzler syndrome, Scleritis, Scleroderma, Serum Sickness, Sjogren's syndrome, Spondyloarthropathy, Still's disease, Subacute bacterial endocarditis (SBE), Susac's syndrome, Sweet's syndrome, Sydenham chorea see PANDAS, Sympathetic ophthalmia, Systemic lupus erythematosis, Takayasu's arteritis, Temporal arteritis (also known as "giant cell arteritis"), Thrombocytopenia, Tolosa-Hunt syndrome, Transverse myelitis, Ulcerative colitis (one of two types of idiopathic inflammatory bowel disease "IBD"), Undifferentiated connective tissue disease different from Mixed connective tissue disease, Undifferentiated

spondyloarthropathy, Urticarial vasculitis, Vasculitis, Vitiligo, and Wegener's granulomatosis.

[0242] In certain embodiments, administration of a STING modulator to a patient in need thereof results in a decrease of cGAS activity. In some embodiments, administration of a STING modulator to a patient in need thereof results in a decrease of STING activity. In some embodiments, compounds used in the provided methods are prepared by chemical synthesis.

[0243] In certain embodiments, the present invention provides a method of inhibiting

STING comprising contacting STING with a provided modulator.

[0244] In certain embodiments, the present invention provides a method of modulating activity of an STING polypeptide, the method comprising contacting the STING polypeptide with a STING modulator designed by the methods disclosed herein, which modulating agent is not a known modulator, substrate, or product of STING.

Kits

[0245] The invention provides a variety of kits for conveniently and/or effectively carrying out methods of the present invention. Typically kits will comprise sufficient amounts and/or numbers of components to allow a user to perform multiple treatments of a subject(s) and/or to perform multiple experiments.

[0246] In one aspect, the present invention provides kits comprising the molecules

(compounds and compositions as described above) of the invention. In one embodiment, the kit comprises one or more functional antibodies or function fragments thereof.

[0247] Kits of the invention may comprise one or more STING parent molecules, or any mimic, analog or variant thereof. Kits may also comprise any of the STING variants, analogs or mutants described herein. The kit may further comprise packaging and instructions and/or a delivery agent to form a formulation composition. The delivery agent may comprise a saline, a buffered solution, a lipid or any delivery agent disclosed herein.

[0248] In one embodiment, the buffer solution may include sodium chloride, calcium chloride, phosphate and/or EDTA. In another embodiment, the buffer solution may include, but is not limited to, saline, saline with 2mM calcium, 5% sucrose, 5% sucrose with 2mM calcium, 5% Mannitol, 5% Mannitol with 2mM calcium, Ringer's lactate, sodium chloride, sodium chloride with 2mM calcium and mannose (See e.g., U.S. Pub. No. 20120258046; herein incorporated by reference in its entirety). In a futher embodiment, the buffer solutions may be precipitated or it may be lyophilized. The amount of each component may be varied to enable consistent, reproducible higher concentration saline or simple buffer formulations. The components may also be varied in order to increase the stability of the compound or composition in the buffer solution over a period of time and/or under a variety of conditions. In one aspect, the present invention provides kits for research applications related to STING activity or cGAMP signaling, provided in an amount effective to study the concomitant signaling pathways when introduced into a target cell. The kits may further comprise a second or further modulator or composition described herein. Such second or further molecules may modulate the immune response or an inflammatory process or comprise one or more therapeutic molecules. In one embodiment, a kit comprises at least one STING polypeptide and at least one cGAMP molecule. In one embodiment, the kits of the present invention comprise packaging and instructions.

Exemplification

[0249] Unless otherwise described in a particular Example, the reagents, protocols and constructs used in each Example are as described below. In each case, one of skill in the art will recognize that variations of particular reagents or procedures would be acceptable equivalents and it is contemplated that these alternatives are considered as part of the present description. The Examples below are intended only to provide specific exemplary enbodiments, and are not limiting.

[0250] The following coordinates have been deposited in the RCSB Protein Data Bank, with which the skilled artisan will be familiar, and correspond to Tables 1-9 incorporated by reference herein. With respect to Tables 1-5, see also Gao, P., et al. Cell 154, 748-762 (2013), including supplementary materials, the entire contents of which are hereby incorporated by reference herein. Furthermore, in the context of Figures 1-3, 5, and 8-10, the data presented in Tables 1-5 of United States provisional patent application no. 61/860,818, filed July 31, 2013, are hereby incorporated by reference.

DMXAA-hSTING^sl62A/Q2661 complex 4QXQ 8

DMXAA-hSTING^{sl62A/G230I/Q2661} complex 4QXR 9

¹ One method of accessing the RCSB Protein Data Bank is online at www.rcsb.org.

[0251] Tables 6-9 are found at the end of the specification and are hereby incorporated by reference herein in their entirety. Table 6 lists atomic structure coordinates for a DMXAA- hSTING^group2 complex as derived from X-ray diffraction from the corresponding crystal. Table 7 lists atomic structure coordinates for a DMXAA-hSTING⁰²³⁰¹ complex as derived from X-ray diffraction from the corresponding crystal. Table 8 lists atomic structure coordinates for a DMXAA-hSTING^sl62A/(^²⁶⁶¹ complex as derived from X-ray diffraction from the corresponding crystal. Table 9 lists atomic structure coordinates for a DMXAA-hSTING^{sl62A/G230I/Q2661} complex as derived from X-ray diffraction from the corresponding crystal.

Plasmid Construction

[0252] The human and murine STING sequences (reference sequences) used in the following Examples were inserted into a modified pMAX-cloning (Amaxa, Cologne, Germany) by standard cloning techniques, in frame with a N-terminal FLAG-tag. Site-directed mutagenesis was performed by the Quikchange method (Agilent, Santa Clara, CA) using Pfu Ultra Hot Start DNA Polymerase (Agilent) or Phusion Polymerase (NEB, Ipswich, MA). Luciferase reporter constructs were as described (Gao et al, 2013). Constructs (Figure 147) were verified by restriction digest and Sanger sequencing (Seqlab, Gottingen, Germany).

Table S7. Primer sequences for STING cloning and mutagenesis

GCCACCATGGATTACAAGGATGACGACGATAAGGTCG 7 hSTINGfw-39bpFlag-GibA

ACATGCCCCACTCCAGCCTGCA

hSTINGrev458-GibA AAATTCCCTTTTTCACACACTGCAG 8 hSTINGfw420-GibA CCCAGCTGAGATCTCTGCA 9

TGTGGTTTGTCCAAACTCATCGAGCTCGATGCGGCCG 10 hSTINGrev-40bp-GibA

CGGTCAAGAGAAATCCGTGCGGAGA

mmSTESiG t481g antisense CCCAATGTAGTATGCCCAGGCCAGCCCG 11 mmSTING t481g CGGGCTGGCCTGGGCATACTACATTGGG 12 mmSTING t496g_a497c CTGGTCATACTACATTGGGGCCTTGCGGTTGATCTTACCA 13 mmSTING 14

TGGTAAGATCAACCGCAAGGCCCCAATGTAGTATGACCAG

t496g a497c antisense

mmSTING c709g_g710c CGACCGTGCTGGCATCAAGAATGCGGTTTATTCCAACAG 15 mmSTING 16

CTGTTGGAATAAACCGCATTCTTGATGCCAGCACGGTCG

c709g_g71 Oc_antisense

mmSTING 17

TCGTAGACGCTGTTGGAAGCAACCCGATTCTTGATGCCAG

t715g a716c antisense

mmSTING t715g_a716c CTGGCATCAAGAATCGGGTTGCTTCCAACAGCGTCTACGA 18 mmSTING 19

CAGAATCTCGTAGACGCTGGCGGAATAAACCCGATTCTTG

a721g a722c antisense

mmSTING a721g_a722c CAAGAATCGGGTTTATTCCGCCAGCGTCTACGAGATTCTG 20 mmSTING a776c antisense GGGGGTGGCGTACGCCAGGATACAGAC 21 mmSTING a776c GTCTGTATCCTGGCGTACGCCACCCCC 22 mmSTING a784g CCTGGAGTACGCCGCCCCCTTGCAGAC 23 mmSTING a784g antisense GTCTGCAAGGGGGCGGCGTACTCCAGG 24 mmSTING a796g antisense CATGGCAAACAGGGCCTGCAAGGGGGTGG 25 mmSTING a796g CCACCCCCTTGCAGGCCCTGTTTGCCATG 26 hSTING 27

AGATATCCGATGTAATATCCCCATGCCAGCCCATGGGC

t484g c485g antisense hSTING t484g_c485g GCCCATGGGCTGGCATGGGGATATTACATCGGATATCT 28 hSTING t484a_a486g GCCCATGGGCTGGCATGGACGTATTACATCGGATATCTG 29 hSTING 30 t484a a486g antisense CAGATATCCGATGTAATACGTCCATGCCAGCCCATGGGC hSTING c485t CCATGGGCTGGCATGGTTATATTACATCGGATATC 31 hSTING c485t_antisense GATATCCGATGTAATATAACCATGCCAGCCCATGG 32

GCCACCATGGATTACAAGGATGACGACGATAAGGTCGACAT 33 hSTINGfw-39bpFlag-GibA

GCCCCACTCCAGCCTGCA

hSTINGrev458-GibA AAATTCCCTTTTTCACACACTGCAG 34 hSTINGfw420-GibA CCCAGCTGAGATCTCTGCA 35

TGTGGTTTGTCCAAACTCATCGAGCTCGATGCGGCCGCGGT 36 hSTINGrev-40bp-GibA

CAAGAGAAATCCGTGCGGAGA

revbefgrou l TGGCAGGATCAGCCGCAG 37 fwbefgrou l CTGCGGCTGATCCTGCCA 38 revbefgroup2 ACAGTCCAATGGGAGGAGAATATACAG 39 fwbefgroup2 CTGTATATTCTCCTCCCATTGGACTGT 40 revbefgroup3 TGGCGTACTCCAGGACACAGG 41 fwbefgroup3 CCTGTGTCCTGGAGTACGCCA 42 revbefgroup4 ACAGCGAGAAGCTGCTGTCAT 43 fwbefgroup4 ATGACAGCAGCTTCTCGCTGT 44 revbeforore266 TGGCGTACTCCAGGACACAG 45 fwbefore266 AGCTTCTGGAGAACGGGCAG 46 fwafter266 TGCCATGTCACAATACAGTCAAGCT 47 revafter266 GGCCTGCTCAAGCCTATCCTC 48

G230R232fw CTGCCCCAGCAGACCGGTGACCGTGCTGGCATCAAGGATC 49

G230R232rev GATCCTTGATGCCAGCACGGTCACCGGTCTGCTGGGGCAG 50 A230R232fw CTGCCCCAGCAGACCGCTGACCGTGCTGGCATCAAGGATC 51

A230R232rev GATCCTTGATGCCAGCACGGTCAGCGGTCTGCTGGGGCAG 52

G230H232fw CTGCCCCAGCAGACCGGTGACCATGCTGGCATCAAGGATC 53

G230H232rev GATCCTTGATGCCAGCATGGTCACCGGTCTGCTGGGGCAG 54 group2toGfw CTGCCCCAGCAGAACGGTGACCGTGCTGGCATCAAGAATC 55 group2toGrev GATTCTTGATGCCAGCACGGTCACCGTTCTGCTGGGGCAG 56

Q266Ifw GTGACATGGCAAACAAAGTTATCAAGGGGGTGGCGTACTCC 57

Q266Irev GGAGTACGCCACCCCCTTGATAACTTTGTTTGCCATGTCAC 58

S162Afw CCCATGGGCTGGCATGGGCATATTACATCGGATATC 59

S162Arev GATATCCGATGTAATATGCCCATGCCAGCCCATGGG 60

G230I 232H_fw CTGCCCCAGCAGACCATTGACCATGCTGGCAT 61

G230I 232H_rev ATGCCAGCATGGTCAATGGTCTGCTGGGGCAG 62

G230I 232R_fw TCCTTGATGCCAGCACGGTCAATGGTCTGCTGGGGCAG 63

G230I 232R_rev CTGCCCCAGCAGACCATTGACCGTGCTGGCATCAAGGA 64

I165Afw GGGCTGGCATGGTCATATTACGCCGGATATCTGCGGCT 65

I165Arev AGCCGCAGATATCCGGCGTAATATGACCATGCCAGCCC 66

G166Sfw CTGGCATGGTCATATTACATCAGCTATCTGCGGCTGATCC 67

G166Srev GGATCAGCCGCAGATAGCTGATGTAATATGACCATGCCAG 68

I235Lfw AGACCGGTGACCGTGCTGGCCTCAAGGATCGGG 69

I235Lrev CCCGATCCTTGAGGCCAGCACGGTCACCGGTCT 70

Q266Ifw GGAGTACGCCACCCCCTTGATAACTTTGTTTGCCATGTCAC 71

Q266Irev GTGACATGGCAAACAAAGTTATCAAGGGGGTGGCGTACTCC 72

Q266Lfiy CGCCACCCCCTTGCTGACTTTGTTTGCCAT 73

Q266Lrev ATGGCAAACAAAGTCAGCAAGGGGGTGGCG 74

Q266Vfw GTACGCCACCCCCTTGGTGACTTTGTTTGCCATGT 75 Q266Vrev ACATGGCAAACAAAGTCACCAAGGGGGTGGCGTAC 76 mSTING_I229Gfw ATGCTGCCCCAGCAAAACGGCGACCGTGCTGG 77 mSTING_I229Grev CCAGCACGGTCGCCGTTTTGCTGGGGCAGCAT 78 mSTING_I229Afw ATGCTGCCCCAGCAAAACGCCGACCGTGCTGG 79 mSTING_I229Arev CCAGCACGGTCGGCGTTTTGCTGGGGCAGCAT 80

[0253] Human STING mutants were assembled from C-terminal mutated constructs

(140-C) and N-terminal reference sequence by Gibson Assembly (NEB) and confirmed by Sanger sequencing. STING^THP1 and STING^R232 cDNAs were cloned from THP1 cells and Peripheral Blood Mononuclear Cells of a voluntary human donor with informed consent, respectively.

Protein Expression and Purification [0254] Unless otherwise specified, sequences used in the following Examples

g to residues aa 140-379 and 155-341 of hSTING^H232, hSTING^R232,

hSTING A230/R232_{? hSTING}group2_{? hSTING}G23CH _hSTINGS162A/Q26« _{and hSTING}S162A/G230I/Q266I. and residues 139-378 and 154-340 of mSTING^R231 were inserted into a modified pRSFDuet-1 vector (Novagen), in which the target protein was separated from the preceding His₆-SUMO tag by an ubiquitin-like protease (ULP1) cleavage site. The gene sequences were subsequently confirmed by sequencing. The fusion proteins were expressed in BL21 (DE3) PJL cell strain. The cells were grown at 37 °C until OD600 reached approx. 0.6. The temperature was then shifted to 18 °C and the cells were induced by addition of isopropyl β-D-l-thiogalactopyranoside (IPTG) to the culture medium at a final concentration of 0.3 mM. After induction, the cells were grown overnight. The fusion proteins were purified over a Ni-NTA affinity column. The His₆- SUMO tag was removed by ULP1 cleavage during dialysis against buffer containing 40 mM Tris-HCl, 300 mM NaCl, pH 7.5. After dialysis, the His₆-SUMO tag was removed by Ni-NTA affinity column and the sample was further fractionated over a gel filtration 16/60 G200

Superdex column. The final sample of hSTING^H232, hSTING^R232 and hSTING^A230/R232 , mSTING^R231, hSTING⁸¹⁰^², hSTING⁰²³⁰¹, _hSTING^sl62A/Q2661, and _hSTING^{sl62A/G230I/Q2661} contain about 13-16 mg/ml protein, 20 mM Tris-HCl, 150 mM NaCl, pH 7.5. All the mutants were cloned and purified using the same protocol as used for preparation of the wild-type protein.

Crystallization

[0255] Crystals were grown in the following Examples using the sitting drop vapor diffusion method and diffraction data collected at synchrotron beam lines. For crystallization of hSTING^H232 (155-341) with c[G(2',5')pA(3',5')p] and c[G(2',5')pA(2',5')p], the protein was incubated with c[G(2',5')pA(3',5')p] (2 mM) or c[G(2',5')pA(2',5')p] (2 mM) and MgCl₂ (5 mM) for 0.5 h at room temperature. The crystals were generated by sitting drop vapor diffusion method at 20 °C, by mixing equal volume reservoir solution (for c[G(2',5')pA(3',5')p]: 0.01 M NiCl₂, 0.1 M Tris, 20% PEG2000, pH 8.5; for c[G(2',5')pA(2',5')p]: 1.6 M NaH₂P0₄, 0.4 M Na₂HP0₄, 0.1 M phosphate-citrate, pH 4.2) with the sample.

[0256] For crystallization of mSTING^R231 (154-340) with c[G(2',5')pA(3',5')p], c[G(3',5')pA(3',5')p] and DMXAA, the protein was incubated with c[G(2',5')pA(3',5')p] (2 mM) or c[G(3',5')pA(3',5')p] (2 mM) or DMXAA (4 mM) for 0.5 h at room temperature. The crystals were generated by sitting drop vapor diffusion method at 20 °C, by mixing equal volume reservoir solution (for c[G(2',5')pA(3',5')p]: 0.2 M di-ammonium tartrate, 20% PEG3350; for c[G(3',5')pA(3',5')p]: 0.2 M sodium formate, 20% PEG3350; for DMXAA: 1.6 M ammonium sulfate, 0.1 M Tris-HCl, pH 8.0) with the samples.

[0257] For crystallization of DMXAA with hSTING mutants (aa 155-341), the protein samples were mixed and incubated with DMXAA (1 :2 molar ratio) for 0.5 h at room temperature before setting up crystals. The crystals were generated by sitting drop vapor diffusion method at 20 °C, by mixing equal volume reservoir solution with the sample. The detailed conditions are listed below: DMXAA-hSTING^group2: 2 M LiCl, 10% PEG6000, 0.01 M CaCl₂, 0.1 M Tris, pH 7.8; DMXAA-hSTING⁰²³⁰¹: 0.2 M Li₂S0₄, 20% PEG 3350, 0.015 mM CYMAL®-7, 0.1 M Tris, pH 8.1; DMXAA-hSTING^sl62A/Q2661: 0.2 M Ca(Ac)₂, 15% PEG3000, 0.01 M L-Proline, 0.1 M NaAc, pH 5.1; DMXAA-hSTING^{sl62A/G230I/Q2661}: 0.2 M Ca(Ac)₂, 15% PEG3000, 0.1 M LiCl, 0.1 M NaAc, pH 5.1. All structures were solved using PHASER, COOT, PHENIX, and REFMAC programs. Structure Determination

[0258] All the diffraction data sets (except mSTING^R231 with DMXAA) in the following

Examples were collected at the Brookhaven National Laboratory, and were indexed, integrated and scaled using the HKL2000 program (Otwinowski and Minor, 1997). The data set for mSTING^R231, hSTING⁸¹⁰^², hSTING⁰²³⁰¹, _hSTING^{sl62A Q2661}, and _hSTING^{sl62A G230I/Q2661} with DMXAA were collected at Argonne National Laboratory and was indexed, integrated and scaled using the RAPD online server. The structure of hSTING^H232 with c[G(2',5')pA(3',5')p] or c[G(2',5')pA(2',5')p] was solved using molecular replacement method in PHASER (McCoy et al, 2007) using the complex structure of hSTING^A230/R232 and c[di-GMP] (PDB: 4F5D) as the search model. For mSTING^R231 with c[G(2',5')pA(3',5')p], c[G(3',5')pA(3',5')p] and DMXAA, the structure of mSTING^R231 and CMA (PDB: 4JC5) was used as the search model. For the cGAMP-STING binary structures, two STING molecules in the STING dimer have equal probability to bind with either G or A moiety of the cGAMP isomers. The electron density also clearly indicated that the cGAMP isomers adopt two alternative conformations. We therefore assigned two conformations with 0.5 occupancy for bound cGAMP isomers.

[0259] The structures of DMXAA-hSTING^group2, DMXAA-hSTING⁰²³⁰¹, DMXAA- hSTING^sl62A/Q2661, and DMXAA-hSTING^{sl62A/G230I/Q2661} were solved using molecular replacement method in PHASER (McCoy et al, 2007) using the structure of hSTING^H232 complex bound to c[G(2',5')pA(3',5')p] (PDB: 4LOH) as the search model.

[0260] The model building was conducted using the program COOT (Emsley et al,

2010) and structural refinement was conducted using the program REFMAC (Murshudov et al., 1997). The statistics of the data collection and refinement are shown in Table SI, S2, and S7.

Isothermal Titration Calorimetry

[0261] The dissociation constants (Kd) and thermodynamic parameters of binding reactions of hSTING^H232 (aa 140-379), hSTING^R232 (aa 140-379), hSTING^A230/R232 (aa 140-379), mSting^R231 (aa 139-378), mSting^A231 (aa 139-378), hSTING^H232 (aa 140-379), hSTING^group2 (aa 140-379), hSTING^G230I (aa 140-379), hSTING^{sl62A Q2661} (aa 140-379), and STING^{sl62A G230I/Q2661} (aa 140-379), mutants with different cGAMP isomers or DMXAA were measured in the following Examples by isothermal titration calorimetry using a MicroCal ITC200 calorimeter at 25°C. First, wild-type and mutant protein samples were dialyzed overnight against working buffer (100 mM NaCl, 30 mM HEPES, pH 7.5) at 4 °C. Then, the protein samples were diluted with working buffer and the lyophilized cGAMP isomers or DMXAA were dissolved in working buffer. The titration was carried out with 16 successive injections of 2.4 μΕ cGAMP isomers or DMXAA, spaced 180s apart, into the sample cell containing the protein solution. The data for mSting^R231 (aa 139-378) and hSTING^S162 (aa 140-379) mutants with DMXAA were collected using the same protocol as used for STING with cGAMP isomers. The detailed concentration for different titrations was listed in Table S3, S4 and S6. The data were fit using the program Origin 7.0 software.

[0262] We observe a mixture of exothermic and endothermic transitions for complex formation of hSTING/mSting complexes with c[G(3',5')pA(3',5')p] (green triangles, Figure 4, and Table S3), primarily endothermic transitions for complex formation of hSTING/mSting complexes with c[G(2',5')pA(2',5')p] (red circles, Figure 4, and Table S3), and exclusively endothermic transitions for hSTING/mSting complexes bound to c[G(2',5')pA(3',5')p] (black squares, Figure 4, and Table S3). Endothermic binding events are not uncommon and may reflect ligand-induced conformational changes in STING that yield significant solvent

reorganization/displacement, often resulting in 'melting' (an endothermic event) and release (an entropically favorable event) of 'restricted' (bound) solvent (Table S3). The distinct

thermodynamic outcome (exothermic versus endothermic) could possibly relate to very subtle structural differences or alternately to the use of distinct folding pathways with defined energy parameters to arrive at the same or a distinct endpoint.

Mice

[0263] Female C57B/6 mice between 6 and 10 weeks of age were purchased from the

Jackson Laboratory and were used for the preparation of bone marrow-derived macrophages in the following Examples. These mice were maintained in the animal facility at the Sloan- Kettering Cancer Institute. All procedures were performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institute of Health. The protocol was approved by the Committee on the Ethics of Animal Experiments of Sloan-Kettering Cancer Institute (protocol number 96-04-017). IRF3 ^{~ ~} and STING mice were generated in the laboratories of Drs. Tadatsugu Taniguchi (University of Tokyo) and Russell Vance (University of California, Berkeley).

Generation of Bone-Marrow-Derived Macrophages

[0264] Female IRF3^_/~, STING^Gt/Gt and WT C57B/6 mice were used for the preparation of bone marrow-derived macrophages in the following Examples. These mice were maintained in the animal facility at the Sloan-Kettering Cancer Institute. Bone marrow cells were cultured in complete medium (CM) in the presence of 5% of supernatant of L929 mouse fibroblasts as conditioned medium providing macrophage colony-stimulating factor (M-CSF) for 7 days. CM is RPMI 1640 medium supplemented with 10% heat-inactivated fetal bovine serum (FBS), 100 U/ml penicillin, 100 μg/ml streptomycin, 0.1 mM essential and nonessential amino acids, 2 mM L-glutamine, 1 mM sodium pyruvate, and 10 mM HEPES-KOH buffer. Cells were fed at day 4 by replacing 50% of the old medium with fresh medium. Cells were plated into 6-well plate (1 million cells per well) at day 7, the day before stimulation.

Generation of Bone Marrow-derived Dendritic Cells

[0265] The protocol for generation of bone marrow-derived dendritic cells was described before (Dai et al., 2014). Bone marrow-derived dendritic cells were generated by culturing bone marrow cells from the tibia and femur of STING mice in complete medium (CM) in the presence of GM-CSF (30 ng/ml, produced by the Monoclonal Antibody Core facility at the Sloan Kettering Institute) for 10 days. CM is RPMI 1640 medium supplemented with 10% heat- inactivated fetal bovine serum (FBS), 100 U/ml penicillin, 100 μg/ml streptomycin, 0.1 mM essential and nonessential amino acids, 2 mM L-glutamine, 1 mM sodium pyruvate, and 10 mM HEPES buffer. Cells were fed every 2-3 days by replacing 50%> of the old medium with fresh medium. Cells were plated into 6-well plate (1 x 10⁶ cells per well) at day 10, the day before retroviral infection. BMDCs (lxlO⁶ cells/well) were infected with retroviruses expressing hSTING (wt and various substitution mutants). 48 hours after retroviral infection, cells were stimulated with DMXAA. Retroviruses Transduction and DMXAA Treatment

[0266] hSTING cDNAs were cloned into pQCXIP-HA vector. In vitro packaging system was used to generate retroviruses according to protocol (Clontech). BMDCs (lxlO⁶ cells/well) were seeded into 6-well plates and infected with retroviruses. 48 hours after retroviral infection, cells were stimulated with DMXAA at a final concentration of 50 μg/ml (Sigma). For real-time PCR analysis, cells were collected at 3 hours post DMXAA treatment. Supernatants were collected at 18 hours post DMXAA treatment. CXCLIO protein level was determined by ELISA.

THP1 Cell Culture

[0267] Human THP1 cells were cultured in RPMI1640 (Life Technologies) containing

10% FBS, 2 mM glutamine (Life Technologies), 1 mM sodium pyruvate (Life Technologies), and 100 U/ml penicillin/streptomycin (Life Technologies). cGAMP Stimulation of Cells

[0268] Bone marrow derived murine macrophages and THP-1 cells were stimulated by incubation with cGAMP isomers at indicated concentrations for 18 hrs, or by Digitonin permeabilization (30 minutes) at indicated concentrations as described (Woodward et al., 2010). Cytokines in supernatants were determined after 18 hrs by ELISA. THP1 cells were plated at 8xl0⁴ cells per 96-well and treated as described above.

RT-PCR analysis ofTHPl Cells

[0269] For RT-PCR analyses in the following Examples, 5xl0⁵ THP1 cells were plated in 12-well dishes and incubated overnight. 12.5 μΜ of cGAMP isomers were applied to the media and cells were harvested at indicated times. RNA samples were isolated and cDNA libraries were generated. KOD Polymerase was used to PCR amplify regions of IFNB1 and CXCLIO and normalized against TUBA IB.

RNA Isolation and Real-time PCR

[0270] Total RNA was extracted from whole-cell lystates with an RNeasy Mini kit

(Qiagen) and reverse transcribed with the First Strand cDNA synthesis kit (Fermentas) in the following Examples. Quantitative real-time PCR was performed in triplicate with the Applied Biosystem 7500 Real-Time PCR Detection System (Life Technologies) using Fast SYBR Green Master Mix and gene-specific primers. Relative expression was normalized to the levels of glyceraldehyde-3 -phosphate dehydrogenase (GADPH).

RT-PCR Analysis

[0271] RNA was extracted and isolated from each sample in the following Examples using TRIzol (Life Technologies), per manufacturer's instructions. Superscript III RT-PCR Kit (Life Technologies) was used for generating cDNA libraries, using oligo-dT primers, per manufacturer's instructions. The following primers were used for PCR:

IFNB1

5 '-GGACCATAGTCAGAGTGGAAATCCTAAG-3 ' (SEQ ID NO.:33)

5 ' -C ACTT AAAC AGC ATCTGCTGGTTGAAG-3 ' (SEQ ID NO.:34)

5 ' -TGGAGATGACGGAGAAGATG-3 ' (SEQ ID NO.:81)

5 ' -TTGG ATGGC AAAGGC AGT-3 ' (SEQ ID NO.: 82)

TUBA1B

5 '-ACCTTAACCGCCTTATTAGCCA-3 ' (SEQ ID NO.:35)

5 '-ACATTCAGGGCTCCATCAAATC-3 ' (SEQ ID NO.:36)

CXCL10

5 '-GCTACCTACATACAATTCCAAACACATAC-3 ' (SEQ ID NO.:37)

5 ' -GT ACTTAATT AC ATGTT ATTCC ATGT AC ACTGAAAAC-3 ' (SEQ ID NO.:38)

5 ' -GTC AGGTTGCCTCTGTCTC A-3 ' (SEQ ID NO.:83)

5 ' -TC AGGG AAGAGTCTGGAAAG-3 ' (SEQ ID NO.:84)

CCL5

5 '-GCCCACGTCAAGGAGTATTTCTA-3 ' (SEQ ID NO.:85)

5 ' -AC ACACTTGGCGGTTCCTTC-3 ' (SEQ ID NO.: 86)

IL-6

5 ' -AGGC ATAACGC ACT AGGTTT-3 ' (SEQ ID NO.:87)

5 ' -AGCTGGAGTC AC AGAAGGAG-3 ' (SEQ ID NO.:88)

GAPDH

5 ' -ATC AAG AAGGTGGTG AAGC A-3 ' (SEQ ID NO.:89) 5 ' -AGAC AACCTGGTCCTC AGTGT-3 ' (SEQ ID NO.:90)

PCR was accomplished using KOD Hot Start DNA polymerase (EMD Millipore) according to manufacturer's instructions. ImageJ (vl .47q) was used for quantitation of amplicons using TUBA1B for normalization.

Cell Culture

[0272] 293T cells (Life Technologies, Carlsbad, CA) were grown in DMEM

supplemented with 10% fetal bovine serum (FBS), 1 mM sodium pyruvate, lx MEM nonessential amino acids and 100 U/ml Penicillin/Streptomycin (Life Technologies).

Luciferase Assay

[0273] HEK293T cells in the following Examples were reverse-transfected with STING expression plasmids and reporter constructs. 12 hrs later, DMXAA was added directly, while cGAMP isomers and c[di-GMP] were delivered with digitonin permeabilization. Luciferase expression was determined after another 12 hrs, or 30 hrs when transfected together with a cGAS-expression plasmid.

[0274] For cGAMP Luciferase Assays, 3xl0⁴ HEK293T cells (Life Technologies,

Carlsbad, CA) per 96-well were reverse-transfected with a mix of pGL3-IFNBl-Gluc (50ng), pLenti-EFl-Fluc (lOng), pMAX-Flag-STING (5ng) and 35 ng empty plasmid (pMAX-cloning; Amaxa, Cologne, Germany) using Trans-IT LTl Reagent (MirusBio, Madison, WI). 12h after transfection, cGAMP isomers (synthesized by Roger Jones) and c[di-GMP] (Invivogen, San Diego, CA) were delivered with digitonin permeabilization as described (Woodward et al, 2010). DMXAA (Sigma) was diluted in fresh medium added to transfected cells. Luciferase expression was determined after 12 h. For stimulation by cGAS, cells were transfected as described above, but instead of empty plasmid pLenti(p)-EFl-Flag-mm-cGAS (WT or nonfunctional E211A mutation) was used, and Luciferase expression was determined 30 h after transfection. In this setting, expression plasmid served as cGAS stimulus at the same time. Cells were lysed in Passive Lysis Buffer. Firefly and gaussia luciferase activities were determined on an En Vision reader (Perkin Elmer, Waltham, MA) using their respective substrates (D-Luciferin and coelenterazine, PJK GmbH, Kleinblittersdorf, Germany) according to standard protocols. IFNBl-Gluc values were normalized to constitutive firefly luciferase values and fold induction was calculated in relation to control-plasmid pMAX-GFP.

[0275] Luciferase assays for DMXAA experiments were performed as described above.

Briefly, 3xl0⁴ 293T cells were reverse-transfected with STING constructs (5 ng per 96-well) and reporter constructs (50 ng pIFNP-Gluc, 10 ng pLenti-EFl-Fluc for normalization, 35 ng pMAX- empty as stuffer, delivered with TransIT-LTl, MirusBio, Madison WI). 12 hours after transfection, medium was replaced with fresh Medium containing DMXAA. 12 hours after stimulation with STING-ligands, cells were resuspended in passive lysis buffer and luciferase activity was determined using the respective substrates Coelenterazine and D-Luciferin (PJK, Kleinblittersdorf, Germany). Gaussia Luciferase values were then normalized to constitutive Firefly Luciferase values (resulting in Relative Light Units, RLU).

ELISA

[0276] CXCL10 was measured using the BD Opteia human IP- 10 ELISA Set according to manufacturer's recommendations. Murine IFN-a was determined by ELISA using antibody RMMA-1 for capture and rabbit-anti-murine IFN-a polyclonal antibody for detection (PBL Interferon Source, Piscataway, NJ). Dose-response curves were fitted and EC₅₀ values were determined with Graphpad Prism (Graph Pad Software Inc., San Diego, CA).

Western Blot Analysis

[0277] BMDMs (1 x 10⁶) were treated with cGAMP linkage isomers. At various times post-stimulation, the medium was removed and cells were collected. Whole-cell lysates were prepared at 2, 4, and 8 h post-treatment. Equal amounts of proteins were subjected to SDS-PAGE and transferred to a nitrocellulose membrane. Phosphorylation of IRF3 was determined using a rabbit polyclonal antibody specific for phosphoserine-396 of IRF3 (Cell signaling). The level of IRF3 was determined by using a rabbit polyclonal antibody against IRF3. Phosphorylation of TBK1 was determined using a rabbit monoclonal antibody specific for phosphoserine-172 of TBK1 (Cell Signaling). The level of TBK1 was determined by using a rabbit monoclonal antibody against TBK1 (Cell Signaling). Anti-glyceraldehyde-3 -phosphate dehydrogenase (GADPH) was used as loading controls.

[0278] BMDCs (1 x 10⁶ cells) were infected with retroviruses carrying WT hSTING and various hSTING mutants. Cells were collected at 2 days post retroviral infection. Whole-cell lysates were prepared by lysing cells in RIP A buffer. Equal amounts of proteins were subjected to SDS-PAGE and transferred to a nitrocellulose membrane. The levels of HA-hSTING in transduced cells were determined by using a mouse monoclonal antibody specific for HA tag (Covance). Anti-glyceraldehyde-3 -phosphate dehydrogenase (GAPDH) was used as a loading control, and was detected using a polyclonal antibody against GAPDH (Cell Signaling).

Example 1: Crystal Structure of c[G(2',5')pA(3',5')p] Bound to hSTING

[0279] The present Example presents the 2.25 A crystal structure of an -186 amino acid human STING polypeptide bound to c[G(2',5')pA(3',5')p].

[0280] The 2.25 A crystal structure of c[G(2',5')pA(3',5')p] bound to the symmetrical dimer of human STING (G230/H232; aa 155-341; termed hSTING^H232) is shown in Figure 1A (x-ray statistics in Table SI). The individual symmetry-related subunits of STING in a ribbon representation are color-coded in magenta and yellow, while the bound c[G(2',5')pA(3',5')p] is shown in a space-filling representation. The bound ligand is positioned in a deep U-shaped cleft between subunits, with the cyclic sugar-phosphate backbone at the base and the purine rings pointing upwards in a parallel alignment (expanded view in Figure IB). The bound U-shaped ligand is further anchored in place by an overhead cap element formed on complex formation by an anti-parallel four-stranded β-pleated sheet (Figure 2A), such that the hSTING dimer completely envelops the bound ligand (Figure 1C, D). Table SI. X-ray Statistics for cGAMP Linkage Isomers with hSTING

[0281] Relates to Figure 1 , 2 and 3.

[0282] The binding pocket is uncharged at its base, while both positive- and negative- charged residues line its walls. The bound c[G(2',5')pA(3',5')p] is anchored by its purine bases being bracketed on either side by Y 167 (Figure IE) and by R238 (whose position is buttressed by Y240), with R238 aligned in the plane and hydrogen bonds to the N7 of one purine, while its guanidinium group stacks over the other purine of the bound cyclic dinucleotide (Figure IE, F, G). The bound ligand is further stabilized through a network of direct and water-mediated hydrogen bonds to the base edges from side chains of hSTING^H232 (Figure IF, G). Amino acids participating in this network and positioned above the bound ligand include N242, S241 and V239 which form water-mediated hydrogen bonds to the 06 of guanosine, while Y163, E260, and Y261 form water-mediated hydrogen bonds together with a direct hydrogen bond from T263 to the NH₂ group of guanosine (Figure IF). The edges of the adenosine base are not involved in hydrogen-bond formation (Figure IF).

[0283] The phosphate backbone and ribose hydroxyls of the cyclic dinucleotide ring system are additionally stabilized through hydrogen bonds. Amino acids participating in this network and positioned below the bound ligand include SI 62 and T267 (Figure IG), with the 3'- OH group of the guanosine hydrogen-bonded to the side chain hydroxyl of SI 62, while no hydrogen-bonding is observed to the 2' -OH of adenosine of c[G(2',5')pA(3',5')p] in the complex (Figure IG). The backbone phosphates of the bound cyclic dinucleotide are recognized by direct contacts from the guanidinium groups of R238 and through water-mediated hydrogen bonds from the hydroxyl groups of T267 and Y240 (Figure IG).

[0284] The four-stranded anti-parallel β-sheet that forms upon c[G(2',5')pA(3',5')p]- hSTING^H232 complex formation (Figure 2A) caps the top of the binding pocket and restricts access to it (Figure 1 A). In addition to hydrogen-bonding between strands across the four- stranded β-pleated sheet, anchoring at either end of the sheet is achieved by salt bridges (Figure 2A). It should be noted that G230 forms part of the outer β-strand of this four- stranded β-sheet (Figure 2A).

Example 2: Comparison of Crystal Structures of c[G(2',5')pA(3',5')p] and c[di-GMP]

Bound to hSTING^H232

[0285] The present Example describes the binding cleft of human STING and presents

"open" and "closed" STING complex structure.

[0286] An exemplary crystal structures of c[di-GMP] bound to the symmetrical dimer of hSTING^H232 (aa 139-379) (PDB: 4EF4; 2.15 A resolution) is shown in Figure 8A, with an expanded view of the ligand binding pocket shown in Figure 8B. Note that the loops protruding over the binding pockets are disordered over half their lengths in the direction of their tips, while the symmetry-related o2 -helices form a larger angle in the V-shaped c[di-GMP] complex (Figure 8A), as compared to the U-shaped c[G(2',5')pA(3',5')p] complex (Figure 1A) with hSTING^H232. Indeed, space filling views of the c[di-GMP] complex indicate that the hSTING^H232 dimer does not encapsulate the bound c[di-GMP] in its complex (Figure IOC, D; termed the Open' STING complex), as it does in space filling views of the c[G(2',5')pA(3',5')p] complex (Figure 1C, D; termed the 'closed' STING complex) with hSTING^H232.

[0287] The intermolecular hydrogen bonds stabilizing complex formation in the exemplary structure of the complex of c[di-GMP] with hSTING^H232 (PDB: 4EF4) are shown in Figure 8E, F. Notably, the side chains of R238 are disordered, unlike the key recognition role they play in the complex of c[G(2',5')pA(3',5')p] with hSTING^H232 (Figure IF, G).

[0288] The superposition of c[di-GMP] bound to the Open' hSTING complex (both subunits in beige) with that for c[G(2',5')pA(3',5')p] bound to the 'closed' hSTING complex (both subunits in green) shows large conformational differences in STING between the two complexes (Figure 2B; rmsd = 3.11 A). Indeed, the separation between the tips of the symmetry related a2-helices decreases from approx. 60 A in the 'open' complex to approx. 38 A in the 'closed' complex. Furthermore, superposition of the bound c[di-GMP] in beige with that of bound c[G(2',5')pA(3',5')p] in green establishes that the purine bases are further apart in the former complex compared to the latter complex (Figure 2C), and presumably facilitate switching of the hSTING^H232 from an 'open' and more flexible (partly disordered loops positioned over the binding pocket) conformation in the c[di-GMP] complex (Figure 8 A) to a 'closed' and more compact (well defined four-stranded β-sheet cap over the binding pocket) conformation in the c[G(2',5')pA(3',5')p] complex (Figure 1A). Furthermore, the bound c[G(2',5')pA(3',5')p] (in green) is positioned slightly deeper in the binding cleft than its bound c[di-GMP] counterpart (in beige) (Figure 2C, top panel). Importantly, the conformational changes propagate to the surface of the STING protein as shown in a stereo view (Figure 2D) highlighting the upper right segment of Figure 2B. Example 3: Similar 'Closed' Conformations Adopted by c[G(2',5')pA(3',5')p] Bound to mSting^R231 and hSTING^H232

[0289] The present Example describes the 1.77 A crystal structure of an -186 amino acid mouse STING polypeptide bound to c[G(2',5')pA(3',5')p].

[0290] We have solved the 1.77 A crystal structure of c[G(2',5')pA(3',5')p] bound to the symmetrical dimer of mSting^R231 (aa 154-340) (Figure 3 A and Table S2). The side chain of R231 of mSting^R231 is shown in green in a stick representation (Figure 3A). Given the high resolution of this complex, the network of hydrogen bonds are clearly visible; the 3'-OH of guanosine of bound c[G(2',5')pA(3',5')p] makes hydrogen bonds with the side chain of S161 and two water molecules (Figure 3B). The guanidinium group of R231 interacts with the backbone phosphates of c[G(2',5')pA(3',5')p] through a bridging water molecule (Figure 3B). Formation of the four- stranded anti-parallel β-pleated sheet acts as a cap over the bound ligand in the complex (Figure 3A).

231

Table S2. X-ray Statistics for cGAMP Linkage Isomers and DMXAA with mSting

^a Highest resolution shell (in A) shown in parentheses.

Relates to Figure 3 and 5.

[0291] We observe excellent superposition of hSTING^H232 (both subunits in green) and mSting^R231 (both subunits in magenta) in its complexes with c[G(2',5')pA(3',5')p] as shown in Figure 3C (rmsd = 0.84 A). The separation between the tips of symmetry related a2 -helices are approx. 38 A for both complexes (Figure 3C). We also observe excellent superposition of the c[G(2',5')pA(3',5')p] dinucleotide in its complexes with hSTING^H232 and mSting^R231 (Figure 3D). Thus, the same c[G(2',5')pA(3',5')p]-STING complex is observed whether a His or Arg occupies this key position. Indeed, the R238, S162 and T267 in hSTING^H232 (Figure 1H) and their conserved counterparts R237, S161 and T266 in mSting^R231 (Figure 3B) are involved in similar hydrogen-bonding interactions with the backbone phosphates and sugar hydroxyl groups in both complexes.

Example 4: c[G(2',5')pA(2',5')p]- and c[G(3',5')pA(3',5')p]-Bound STING Complexes

Both Adopt 'Closed' Conformations

[0292] The present Example describes the 1.9 A crystal structure of an ~186 amino acid human STING polypeptide bound to c[G(2',5')pA(2',5')p]. The present Example also describes the 2.1 A crystal structure of an -186 amino acid mouse STING polypeptide bound to c[G(3',5')pA(3',5')p].

[0293] We also crystallized the two other cGAMP linkage isomers c[G(2',5 ')ρΑ(2',5 ')ρ] and c[G(3',5')pA(3',5')p] with hSTING^H232 and mSting^R231, respectively. We solved a 1.9 A crystal structure of c[G(2',5')pA(2',5')p] with hSTING^H232 (aa 155-341) (Figure 3E and Table SI) and a 2.1 A crystal structure of c[G(3',5')pA(3',5')p] with mSting^R231 (aa 154-340) (Figure 3F and Table S2). The structures of both complexes adopt the 'closed' conformation as reflected by the positioning of the ligands in the binding pocket, the separation between the tips of the a2- helices by approx. 38 A, and the formation of the four-stranded anti-parallel β-sheet cap over the bound ligands (Figure 3E, F). [0294] The crystal structures of c[G(2',5')pA(2',5')p] (in red) and c[G(2',5')pA(3',5')p]

(in green) in their bound complexes with hSTING^H232 superimpose with an rmsd of 0.59 A (Figure 9A), with the 3'-OH groups of bound c[G(2',5')pA(2',5')p] forming water-mediated hydrogen bonds to the hydroxyls of SI 62 and T267 (Figure 9B). The crystal structures of c[G(3',5')pA(3',5')p] (in cyan) and c[G(2',5')pA(3',5')p] (in magenta) in their bound complexes with mSting^R231 superimpose with an rmsd of 0.25 A (Figure 9C), with the 2'-OH groups of bound c[G(3',5')pA(3',5')p] forming direct hydrogen bonds to the hydroxyls of T262 (Figure 9D). The bound c[G(2',5')pA(2',5')p] (in red) is positioned somewhat deeper in the binding pocket than c[G(3',5')pA(3',5')p] (in cyan) (Figure 9E).

Example 5: ITC Binding Studies of hSTING^H232 and its Mutants with Linkage Isomers of cGAMP

[0295] The present Example describes isothermal titration calorimetric (ITC) binding curves for a human STING polypeptide bound with various linkage isomers of cGAMP including c[G(2',5')pA(2',5')p], c[G(3',5')pA(3',5')p], or c[G(2',5')pA(3',5')p].

[0296] We recorded the isothermal titration calorimetric (ITC) binding curves for hSTING^H232 (aa 140-379) with three linkage isomers of cGAMP as shown in Figure 4A. The binding curves are exothermic for complex formation with c[G(2',5')pA(2',5')p] (red circles) and c[G(3',5')pA(3',5')p] (green triangles), and endothermic for complex formation with c[G(2',5')pA(3',5')p] (black squares; K_D = 5.3 μΜ). The thermodynamic K_D, AG, AH and TAS parameters for these complexes are listed in Table S3.

Table S3. ITC Parameters for Binding of cGAMP Linkage Isomers to hSTING and mSting Alleles

c[G(2',5')pA(2',5')p] 0.62 2.5 ± 0.1 -7.52 -7.15 +0.37 c[G(2',5')pA(3',5')p] 0.54 5.3 ± 0.5 -7.19 +2.62 +9.81

hSTING with cGAMP Isomers

Protein: 0.2 mM; Ligands: 0.9 mM; Buffer: 30 mM HEPES, 100 mM NaCl, pH 7.5; T: 25 °C

hSTING with cGAMP Isomers

Protein: 0.2 mM; Ligands: 0.9 mM; Buffer: 30 mM HEPES, 100 mM NaCl, pH 7.5; T: 25 °C

c[G(3',5')pA(3',5')p] 0.42 1.34 ± 0.14 -8.01 -7.36 +0.65 c[G(2',5')pA(2',5')p] a

c[G(2',5')pA(3',5')p] 0.41 0.34 ± 0.04 -8.80 +3.63 +12.43 a Values could not be measured due to precipitation of complex

Relates to Figure 4.

[0297] We also recorded ITC binding curves for complex formation of

c[G(2',5')pA(3',5')p] with mutants of hSTING^H232 that participate in intermolecular contacts on complex formation. For this linkage isomer, cGAMP binding is completely lost (Figure 4B and Table S4) for the R238A mutant involved in cyclic dinucleotide base N7 and backbone phosphate recognition (Figure IE, F, G), as well as for the Y240A, N242A and E260A

(significantly reduced) mutants involved in water-mediated guanosine base edge recognition (Figure IF). The impact of mutating the polar Thr and Ser residues involved in intermolecular hydrogen bond formation is more nuanced, with no effect on binding affinity for the T267A mutant, a modest reduction for the S162A mutant and a more pronounced reduction for the T263A mutant (Figure IB). The thermodynamic parameters are listed in Table S4.

Table S4. ITC Parameters for Binding of c[G(2',5')pA(3',5')p] to hSTING^H232 Mutants hSTING Mutants with c[G(2',5')pA(3',5')p]

Protein: 0.3 mM; Ligands: 1.5 mM; Buffer: 30 mM HEPES, 100 mM NaCl, pH 7.5; T: 25 °C

Relates to Figure 4.

ITC Binding Studies ofhSTING^R232 and hSTING⁴²³⁰^²³² With Linkage Isomers of cGAMP

[0298] The corresponding ITC-based thermodynamic parameters were also recorded for complex formation of cGAMP linkage isomers with hSTING^R232 and hSTING^A230/R232 (aa 140- 379) (Figure 4C, D, respectively). The 2', 5 '-containing linkage isomers of cGAMP exhibited increased binding affinity by about an order of magnitude for STING variants with R232 compared to H232, while the corresponding binding affinity increase was about 4-fold for the all-3',5' linkage isomer of cGAMP (Table S3), with endothermic titration patterns observed for all binding curves, except for an exothermic titration pattern for c[G(3',5')pA(3',5')p] with hSTING^R232 (Figure 4C). The dissociation constants for c[G(2',5')pA(3',5')p] bound to hSTING^R232 and hSTING^A230/R232 were K_D = 0.11 μΜ and 0.16 μΜ, respectively (Table S3).

ITC Binding Studies of mSting and mSting with Linkage Isomers of cGAMP

[0299] The corresponding ITC-based thermodynamic parameters for complex formation of cGAMP linkage isomers with mouse Sting^R231 (I229/R231; aa 139-378) are plotted in Figure 4E, with observed K_D values similar to those observed for hSTING^A230/R232 (Table S3). The ITC titrations for mSting ^A231 with the various cGAMP linkage isomers are plotted in Figure 4F, with the observed K_D values listed in Table S3. The dissociation constants for c[G(2',5')pA(3',5')p] bound to mSting^³¹ was K_D = 0.34 μΜ (Table S3).

Example 6: Crystal Structure of DMXAA Bound to mSting¹*"¹

[0300] The present Example describes a 2.4 A crystal structure of an -186 amino acid mouse STING polypeptide bound to 5,6-dimethylxanthenone-4-acetic acid (DMXAA).

[0301] Reported antiviral small molecules reported to date that target mSting include 5,6- dimethylxanthenone-4-acetic acid (DMXAA) (Figure 5 A) (Conlon et al. 2013; Kim et al. 2013) and lO-carboxymethyl-9-acridine (CMA) (Figure 10A) (Caviar et al. 2013), with DMXAA and CMA showing species specificity for mouse but not human STING. The mode of binding of DMXAA and CMA to mSting is of interest for structure-based design of agonists and antagonists of hSTING with value as anti-cancer/anti-viral vaccine adjuvants and antiinflammatory compounds, respectively.

[0302] We solved the 2.4 A crystal structure of DMXAA bound to mSting^R231 (aa 154-

340) (x-ray statistics in Table S2), with the complex containing two molecules of DMXAA per mSting^R231 dimer (Figure 5B). The aromatic rings of the two DMXAA moieties are aligned in parallel but are not stacked on each other. The details of the intermolecular contacts in the complex are shown in Figure 5C, with the ketone groups of DMXAA forming direct hydrogen bonds to the side chain of T266, while the carboxylate moieties of the ligand are anchored through direct hydrogen bonds to the side chains of R237 and T262. In addition, the adjacent aromatic methyl groups of DMXAA form a hydrophobic patch with side chains of LI 69 and 1234 of mSting, while the non-substituted aromatic edges (positions 7 and 8) of DMXAA are positioned opposite 1164 (Figure 5C). A four-stranded anti-parallel β-pleated sheet forms a cap over the binding pocket indicative of formation of a 'closed' conformation on complex formation, consistent also with DMXAA exposure leading to type I IFN pathway activation via mSting (Conlon et al. 2013; Kim et al. 2013).

[0303] Finally, the mSting moieties bound to DMXAA (both subunits in biscuit) and to

CMA (both subunits in yellow) (PDB: 4JC5) superpose well on each other (rmsd = 0.75 A) representing the 'closed' conformation for both complexes (Figure 10B). By contrast, the mSting moieties bound to DMXAA (both subunits in biscuit) and to c[G(2',5')pA(3',5')p] (both subunits in magenta) show differences upon superposition despite both adopting the 'closed' conformation (rmsd = 2.21 A) with the separation between the tips of the a2-helices increasing from approx. 42 A in the former complex to approx. 38 A in the latter complex (Figure 5D). Superposition of the mSting^R23 Abound DMXAA (in salmon) and c[G(2',5')pA(2',5')p] (in magenta) ligands emphasize the different orientations adopted by these bound ligands within the same binding pocket (Figure 5E). Example 7: cGAMP Isomers Activate Type I IFN Pathway Through the STING/IRF3 Pathway

[0304] The present Example describes a requirement for STING activation by cGAMP isomers to induce phosphorylation of Tbkl and IrO.

[0305] To test whether cGAMP isomers elicit an innate immune response in murine macrophages, we recorded simple dose-response of cultured bone -marrow-derived macrophages (BMDMs) by addition of increasing concentrations of c[G(2',5')pA(2',5')p],

c[G(2',5')pA(3',5')p] and c[G(3',5')pA(3',5')p] to the medium, and assaying 4 h post-treatment. Using real-time reverse transcription PCR (qPCR) analysis to monitor induction of Ifnbl, 116, and Ccl5, we determined that exposure of BMDMs to 20 μΜ c[G(3',5')pA(3',5')p] elicited the strongest induction among the three isomers, with Ifnbl, 116 and Ccl5 mRNA levels increased by 1024-, 2624-, and 38-fold, respectively, relative to mock-treatment (Figure 6A). While c[G(3',5')pA(3',5')p] was the most potent compound, the differences between it and the other two isomers did not exceed three-fold. BMDMs isolated from IrO^"7" mice had reduced induction of Ifnbl, 116, and Ccl5 upon exposure to cGAMP isomers, thereby indicating the involvement of IrO-dependent type I IFN response pathway (Figure 6B).

[0306] Western blot analysis further demonstrated that cGAMP isomers induced phosphorylation of Tbkl and IrO at 2 and 4 h post-treatment of BMDMs (Figure 11). Consistent with our qPCR results, incubation of BMDMs with c[G(3',5')pA(3',5')p] also showed the highest levels of Tbkl and IrO protein phosphorylation compared to the two other isomers (Figure 11). To test whether mSting is required for cGAMP-induced Tbkl and IrO

phosphorylation, we compared type I IFN response in BMDMs derived from wild-type and Goldenticket (Gt) mutant mice (Sting ), which carry a I199R missense mutation in exon 6 of the mSting gene resulting in no detectable protein by Western blot analysis of BMDMs

(Rasmussen et al. 2011). We observed that cGAMP-induced Tbkl and IrO phosphorylation was absent from mSting-deficient cells (Figure 11). We conclude that cGAMP treatment of BMDMs triggers type I IFN and pro-inflammatory cytokine/chemokine via the mSting/IrO -dependent pathway. The strongest responses for mSting were seen for cGAMP derivatives comprising the non-metazoan all-3 ',5 '-linkage isomer produced by bacteria, which was unexpected, considering the recent report suggesting that the natural c[G(2',5')pA(3',5')p] was the highest affinity ligand for hSTING (Zhang et al. 2013).

[0307] Therefore, we also evaluated hSTING activation and its dependence on cGAMP isomer concentration. We assayed type I IFN and chemokine production in human THPl cells by ELISA and RT-PCR analysis delivering cGAMP isomers by addition to the medium without or with Digitonin (Dig) permeabilization. In comparison to the murine system, which slightly favored the bacterial c[G(3',5')pA(3',5')p], the non-natural c[G(2',5')pA(2',5')p] stimulated THPl cells 2.9- or 4.8-fold more effectively than the metazoan second messenger

c[G(2',5')pA(3',5')p] or c[G(3',5')pA(3',5')p], respectively (Figure 6C and D, left panels, Table S5). Measuring transcriptional activation of hSTING-dependent IFN response genes by the various cGAMP linkage isomers (Figure 6E) confirmed the ELISA results. As early as 2 h, we detected by RT-PCR that c[G(2',5')pA(2',5')p] stimulated expression of IFNB1 and CXCL10 the most. Digitonin-mediated cell permeabilization significantly increased and enhanced sensitivity to all cGAMP isomer in BMDM and THPl cells (Fig. 6C and D, right panels, Table S5). In THPl cells, there was no difference in the EC50 values obtained for c[G(2',5')pA(2',5')p] and c[G(2',5')pA(3',5')p] exposure.

Table S5. Effective concentration (EC₅₀) values of ELISA dose response curves for BMDM and THPl stimulation with cGAMP linkage isomers

THP1 - CXCL10, +Digitonin (refers to Fig. 6D right panel)

EC₅₀ (μΜ) 0.12 0.14 0.33

95% CI (μΜ) 0.09 - 0.16 0.12 - 0.16 0.28 - 0.39

Related to Figure 6.

Example 8: Mutagenesis of hSTING and mSting Identified Amino Acids Important for Its

Ligand-Binding-Induced IFN Pathway Activation

[0308] The present Example describes human STING amino acid residues important for ligand binding and IFN pathway activation.

[0309] To determine the functional importance of individual amino acids that interacted with c[G(2',5')pA(3',5')p] in the crystal structure, we generated Ala point mutants of specific

H232 R231

residues within hSTING , as well as of the corresponding mutations in mSting , and tested their activities in human HEK293T cells using an IFN-sensitive luciferase reporter assay (Burdette et al. 2011; Gao et al. 2013). STING expression plasmids and IFNB1 luciferase reporter constructs were co-transfected followed by Dig-mediated delivery of cGAMP isomers (Figure 7A), or co-transfected with wild-type or catalytic mutant (E211A) cGAS in the absence of exogenous cGAMP addition (Figure 7B) (Gao et al. 2013). Human mutant STING variants with amino acid substitutions of either of Y167A, R238A, Y240A, or E260A, as well as their murine counterparts, were no longer able to stimulate the IFN-pathway. Notably,

hSTING^H232/N242A induced no measurable IFN reporter activity, whereas mSTING^R231/N241A was only slightly impaired in its response. Mutants S162A and T267A of hSTING^H232 largely

tI232/T263^

retained their normal function, whereas hSTING showed reduced activation (Figure

7A). Dose-response studies of hSTING^H232 (Figure 12) revealed no significant differences in stimulation between c[G(2',5')pA(2',5')p] and c[G(2',5')pA(3',5')p] and a lesser response to c[G(3',5')pA(3',5')p]. However, the hSTING^H232/T263A mutant shows a gain in sensitivity to c[G(3',5')pA(3',5')p] compared to its response to 2',5' linkage isomers. The S162A and T267A hhSSTTIINNGG^H232 mmuuttaannttss rreespond similarly to hSTING , also showing a weaker response to c[G(3',5')pA(3',5')p]. [0310] Given the recent report of mSting and hSTING variants with distinct responsiveness (Diner et al. 2013), we sequenced hSTING DNAs derived from 8 Caucasians and our THP1 cells. All samples encoded R232 in both alleles; additionally hSTING^THP1 contained three additional point mutations (H72R, G230A, and R293Q) as reported before. We compared the cGAMP-dependent IFN-response for hSTING^H232, hSTING^R232, hSTING^THP1 and mSting^R231, and found that the prevalent hSTING^R232 was several-fold more responsive to all cGAMP isomers when compared to hSTING^H232, with the order of cGAMP isomer sensitivity remaining the same (Figure 7 and 12E, F). hSTING^THP1 and wild-type mSting^R231 displayed slightly reduced overall cGAMP sensitivity compared to hSTING^R232.

[0311] To complement our mutagenesis study of the cGAMP isomer response, we tested c[di-GMP] and DMXAA (Fig. 7C and D). While both ligands stimulated mSting, nearly all

R232 XHP 1

hSTING variants were non-responsive except for hSTING and hSTING ^" , which showed a residual response to high concentrations of c-di-GMP) (Fig. 7C and 12). Moreover, mSting mutants defective for recognition of all cGAMP isomers also failed to recognize c[di-GMP] and DMXAA. Mutants N241A and T262A of mSting were less responsive to c[di-GMP] and

DMXAA compared to cGAMPs, whereas mSting (T266A) showed a moderately enhanced recognition of c[di-GMP] over DMXAA.

Example 9: S162A Mutant by hSTING is Activated by DMXAA

[0312] The present Example describes a point mutation in human STING that renders it sensitive to DMXAA.

[0313] Strikingly, we found that the single point mutant S162A enabled recognition of

DMXAA by human STING (Figure 7D, left panel), while not restoring c[di-GMP]

responsiveness (Figure 7C, left panel). In both hSTING^H232 and hSTING^R232 background, the S162A mutation enabled DMXAA recognition with near-identical dose-responses (Figure 13C, D). In contrast, the differences in recognition of cGAMP isomers and c[di-GMP] were only slightly altered or unchanged compared to the respective SI 62 variants (Figure 14B). Noticeably, IFN induction was not observed in cellular assays for the SI 62V and SI 621 mutants of hSTING or hSTING , which contain bulkier hydrophobic amino acids compared to Ala at position 162 (Figure 14A).

[0314] ITC-based binding studies confirmed that mSting^R231 bound DMXAA as reported previously (Figure 14E) (Kim et al, 2013), as did S162A (and S162V) mutants in a hSTING^R232 and hSTING^H232 context bound DMXAA (Figure 7F, G).

[0315] Table S6. ITC Parameters for Binding of DMXAA to hSTING Containing

S162A and S162V Mutants in a R232 and H232 context

Relates to Figure 7E, F and G.

Example 10: The Lid Region of the Ligand-Binding Pocket Is Important for DMXAA Recognition

[0316] Within STING, DMXAA (Figure 15A) and c[G(2',5')pA(3',5')p] share the same ligand binding pocket (Gao et al, 2013b), which in human and mouse proteins is composed of identical amino acids. Despite the fact that human and mouse STING C-terminal domains (CTD, aa 140-379) exhibit -76% amino acid identity (Figure 19), DMXAA only binds and activates mSTING and has no effect on hSTING (Conlon et al, 2013; Kim et al, 2013). Therefore, the non-conserved residues between the two species that are located outside the DMXAA-binding pocket must play a role for distinct DMXAA recognition. We subdivided the non-conserved residues located in the STING CTD into four groups (labeled as group 1 to group4, hSTING^{groupl" 4}). We then substituted hSTING residues with their mSTING counterparts for each of the four groups (Figure 19). These residues are located either along the dimer interface or within the regions that undergo large conformational changes during the Open' to 'closed' transition associated with complex formation. We also generated a construct containing the combined substitution in all four groups (hSTING^group1234).

[0317] We performed isothermal titration calorimetry (ITC) experiments to measure the

DMXAA-binding affinity of hSTING CTD (aa 140-379) containing various group substitutions. hSTING^group1234 showed a comparable exothermic binding curve and binding affinity (K_D: 0.69 μΜ) (Figure 15B) to mSTING (K_D: 0.49 μΜ) (Gao et al, 2013b). Similar to wild-type (wt) hSTING protein, no detectable binding to DMXAA was observed for the isolated group 1, group3, or group4 substitutions of hSTING (Figure 20A). Only group2 substitutions of hSTING exhibited detectable endothermic binding with DMXAA (K_D: 3.12 μΜ; Figure 15C).

[0318] To validate the binding results, we used an IFN-β luciferase reporter assay to further test the responsiveness of hSTING group substitutions to DMXAA stimulation in human 293T cells, which lack endogenous STING expression. Full-length hSTING (wt and

substitutions) and mSTING (wt) constructs were used for this cellular assay, and were expressed at moderate levels allowing ligand-dependent activation of IFN-β promoter. We confirmed that mSTING-transfected 293T cells responded to DMXAA, while hSTING-transfected cells did not (Figure 15D, left panel). Consistent with the ITC results among the individual group

substitutions, only the hSTING^group2 substitutions showed responsiveness to DMXAA (Figure 15D, middle panel). Inversely, removing the group2 substitutions from the combined group 1234 substitutions (hSTING^group134) strongly diminished DMXAA activation, while loss of any of the other groups was tolerated (Figure 15D, right panel). These results indicate that group2 residues from mSTING, which are located within the lid region of the binding pocket, play an a role in DMXAA recognition. Example 11: Crystal Structure of DMXAA Bound to hSTING¹

[0319] We proceeded to solve the crystal structure of DMXAA bound to hSTING⁸™"¹³²

(aa 155-341) at 1.88 A resolution (x-ray statistics in Table SI) with the complex containing two molecules of DMXAA per hSTING^group2 dimer (Figure 15E). The results were similar to what we observed for the complex of mSTING and DMXAA, described above. The four-stranded antiparallel β-pleated sheet formed a lid covering the binding pocket, indicative of formation of a 'closed' conformation of STING on complex formation, which is consistent with the conclusions drawn from our ITC (Figure 15B, C) and IFN-P-dependent luciferase reporter (Figure 15D) results. Rather than being stacked on each other, the aromatic rings of the two DMXAA moieties are aligned in parallel, with complex formation mediated by both intermolecular van der Waals contacts and hydrogen bond interactions. The details of the intermolecular contacts in the complex are shown in Figure 15F, with the ketone and ether groups of DMXAA forming direct hydrogen bonds to the side chain of T267 and T263, respectively. The carboxylate moieties are anchored through direct hydrogen bonds to the side chains of R238 and T263 and through water- mediated hydrogen bonds to Y240. In addition, the adjacent aromatic methyl groups (positions 5 and 6) of DMXAA form a hydrophobic patch with side chains of LI 70 and 1235, whereas the non- substituted aromatic edges (positions 7 and 8) of DMXAA are positioned opposite 1165. We observed excellent superposition of hSTING^group2 and mSTING in their complexes with

DMXAA as shown in Figure 20B (rmsd: 0.95 A).

[0320] To elucidate the molecular basis underlying DMXAA species selectivity, we compared the structure of the hSTING^group2-DMXAA complex with those of the hSTING- c[G(2^,,5^*)pA(3^*,5^,)p] (Gao et al, 2013a) and mSTING-DMXAA (Gao et al, 2013b) complexes. We found that in the hSTING^group2-DMXAA structure, the side chain of the substituted residue 1230 (G230 in wt protein) is located in a hydrophobic pocket composed of residues from both the four-stranded antiparallel β-sheet region (R232, 1235, R238, and Y240) and the adjacent long a- helix (L170 and 1171) (Figure 15G). The amino acids that form the hydrophobic pocket are identical between human and mouse proteins. This same structural feature was also found in the mSTING-DMXAA structure (Figure 20C). In the structure of the hSTING-c[G(2^,,5^*)pA(3^*,5^,)p] complex, the corresponding position to 1230 (or 1229 in mSTING) is G230, which results in the loss of the hydrophobic interactions found in the other two structures. This isoleucine-mediated hydrophobic interaction may help stabilize the β-sheet and other parts of the protein, facilitating DMXAA-mediated formation of the 'closed' conformation by mSTING or hSTING^group2, thereby explaining the absence of complex formation by wt hSTING with a glycine at this position.

Example 12: G230 of hSTING and 1229 of mSTING are Contributors to Differential DMXAA Recognition

[0321] To support our conclusions based on our structural findings above, we generated the G230I single substitution in hSTING and tested its IFN-β induction activity using the luciferase assay. Indeed, hSTING⁰²³⁰¹ alone was sufficient to mimic the effects observed for hSTING^group2, resulting in almost identical IFN-β induction as hSTING^group2 (Figure 16A). Using the same method, reverse substitutions on mSTING (I229G or I229A) were also generated and tested. As expected, mSTING^I229G and mSTING^I229A showed a significant decrease in DMXAA- mediated IFN-β induction (Figure 16B).

[0322] We also solved the crystal structure of DMXAA bound to hSTING⁰²³⁰¹ (aa 155-

341) at 2.51 A resolution (x-ray statistics in Table SI), with hSTING⁰²³⁰¹ in the complex forming a 'closed' conformation (Figure 16C). The detailed intermolecular contacts in the complex (Figure 21 A) are similar to those observed for the hSTING^group2-DMXAA structure (Figure 15F). We observed excellent superposition of hSTING⁰²³⁰¹ and hSTING^group2 in their complexes with DMXAA, as shown in Figure 21B (rmsd: 0.61 A). The 1230 residue, which is positioned within a hydrophobic pocket (Figure 16D), forms the same intramolecular contacts as observed in the structures of the hSTING^group2 -DMXAA (Figure 15G) and mSTING-DMXAA (Figure 20C) complexes. Taken together, our structural and functional data strongly demonstrate that the substitution of Gly with He at aa 230 results in the gain of function of hSTING for DMXAA recognition. Example 13: liSTING^""¹ is Activated by DMXAA

[0323] Examples 1-8 identify a point substitution (S162A) placed within the cyclic- dinucleotide-binding site of hSTING that confers partial sensitivity to the otherwise mouse- specific drug DMXAA (Gao et al, 2013b). Guided by the structures of complexes of hSTING substitutions with DMXAA, we next tested additional substitutions within the ligand-binding pocket to identify more constraints that would help in the design of future modifications on DMXAA. We generated five new substitutions (G166S, I235L, Q266I, Q266L, Q266V) in hSTING (Figure 19) to either enhance the hydrophobic interaction or introduce additional hydrogen bonds with DMXAA. Initial IFN-β induction results showed that only the Q266I substitution in hSTING conferred DMXAA sensitivity at a level similar to that observed for the SI 62 A substitution (Figure 17A). Q266L resulted in a less pronounced gain of DMXAA- mediated IFN-β induction, while G166S, I235L and Q266V showed no effects (Figure 17A). It should be noted that neither S162A nor Q266I substitutions alone were able to introduce IFN-β responsiveness to DMXAA at a level comparable to mSTING (Figure 17B). We therefore tested whether the S162A/Q266I double substitution would augment DMXAA recognition, and indeed observed an enhanced DMXAA-induced IFN-β induction similar to mSTING (Figure 17B). We further validated the luciferase reporter results by testing the binding affinity for hSTING^sl62A, hSTING^Q2661 and STING^sl62A/Q2661 (aa 140-379) with DMXAA using ITC. These results confirmed that hSTING^{sl62A Q2661} binds to DMXAA with higher affinity (K_D: 1.99 μΜ) (Figure 18C) when compared to either hSTING^sl62A (Figure 21C) or hSTING^Q2661 (Figure 2 ID).

[0324] Besides the prevalent allelic hSTING variant (R71/G230/R232/R293, hSTING^R232), four major non-synonymous variants are found in high frequencies with

R71H/G230A/R293Q (hSTING^HAQ) is present in 20.4%, R232H (hSTING^H232) in 13.7%, G230A/R293Q (hSTING^AQ) in 5.2%, and R293Q (hSTING^Q293) in 1.5% of the human population (Yi et al, 2013). To determine whether the S162A and Q266I substitutions were effective in all natural human STING variants, we generated the respective single and double substitutions for all major hSTING alleles (listed in Figure 17D) and tested them for DMXAA recognition (Figure 17E). The S162A/Q266I double substitution was able to induce DMXAA responsiveness in all hSTING alleles, whereas single substitutions were only effective in hSTING^{K i} and hSTING^{H i} . This was further validated by titration of DMXAA concentrations (Figure 17B for hSTING^R232, Figures 22A and 22B for other hSTING alleles), which showed a variable maximal IFN-β induction for different alleles, but clear sigmoidal dose-responses that diverges by less than one order of magnitude in their EC50. Taken together, the Q266I substitution renders hSTING responsive to DMXAA. Further, hSTING containing Q266I and S162A substitutions led to a DMXAA-dependent IFN-β reporter response close to that observed for mSTING.

Example 14: Crystal Structure of DMXAA Bound to hSTING

[0325] To better understand how S162A and Q266I substitutions facilitate the IFN induction of hSTING by DMXAA, we solved the co-crystal complex of DMXAA with hSTING^sl62A/Q2661 (aa 155-341) at 2.42 A resolution (x-ray statistics in Table SI). The complex adopts the 'closed' conformation as reflected by the positioning of two DMXAA in the binding pocket and the formation of the four-stranded antiparallel β-sheet lid over the bound ligands (Figure 17F). The crystal structures of hSTING^sl62A/Q2661 and hSTING⁰²³⁰¹ in their bound complexes with DMXAA superimpose with an rmsd of 0.70 A (Figure 22C). The details of the intermolecular contacts in the complex are shown in Figure 22D, with the same intermolecular hydrogen bonding interaction network as observed in hSTING^group2 -DMXAA (Figure 15F) and hSTING^G230I-DMXAA (Figure 21 A) complexes. The substituted 1266 side chain forms a hydrophobic patch together with the side chains of 1165, LI 70 and 1235, which fully covers the aromatic methyl groups (positions 5 and 6) and the non-substituted aromatic edges (positions 7 and 8) of DMXAA (Figure 17G). The substituted A 162 side chain is juxtaposed to the aromatic edges lining the other side (positions 1 and 2) of DMXAA, forming additional hydrophobic interactions (Figure 17G). SI 62 A and Q266I substitutions increase the binding affinity between hSTING and DMXAA and apparently assist hSTING to overcome the energy barrier from an Open' to a 'closed' conformation. Based on the information on these two point substitutions in hSTING, it should be feasible to apply structure-guided approaches to design DMXAA analogs targeting hSTING. Example 15: hgTING^{M,,ZA lT iM,1/w ,,M} is more Sensitive to DMXAA than mSTING in IFN-β Induction

[0326] We next tested whether combining the G230I substitution with the binding-pocket substitutions S162A/Q266I would further enhance hSTING sensitivity to DMXAA. We generated the triple mutant of hSTING and tested its binding to DMXAA by ITC, as well as IFN induction by DMXAA in transfected cells. The ITC titration for hSTING^{sl62A/G230I/Q2661} with added DMXAA is plotted in Figure 18 A, and showed a higher binding affinity (K_D: 0.99 μΜ) than that observed for hSTING^group2 (K_D: 3.12 μΜ) (Figure 15C) or STING^sl62A/Q2661 (K_D: 1.99 μΜ) (Figure 17C), indicating that all three substitutions individually contribute to an increased DMXAA sensitivity. This increase in affinity translates to synergistic functional effects based on our luciferase reporter assays in which hSTING^{sl62A G230I/Q2661} showed approximately two orders

of magnitude higher sensitivity than hSTING , as well as an order of magnitude higher than either hSTING^sl62A/Q266I or mSTING for the IFN-β induction by DMXAA (Figure 18B).

[0327] We also solved the crystal structure of DMXAA bound to STING^{sl62A/G230I/Q2661}

(aa 155-341) at 2.37 A resolution (x-ray statistics in Table SI) in the 'closed' conformation (Figure 18C). As expected, we observed both the hydrophobic pocket surrounding 1230 (Figure 18D), which is the same as in the hSTING^G230I-DMXAA complex (Figure 16D), as well as the hydrophobic interactions within the DMXAA binding pocket (Figure 18E), which is the same as in the hSTING^sl62A/Q266I-DMXAA complex (Figure 17G).

Table S7. X-ray Statistics for DMXAA with hSTING Mutants

Beam line APS-ID24C APS-ID24C APS-ID24C APS-ID24C

Wavelength 1.550 1.550 1.550 1.550

Space group 6j22 P6 P6

Unit cell

a, b, c (A) 62.9, 62.9, 196.1 36.6, 77.9, 79.6 148.0, 148.0, 36.1 148.6, 148.6, 36.2 , β, γ θ 90.0, 90.0, 120.0 90.0, 99.0, 90.0 90.0, 90.0, 120.0 90.0, 90.0, 120.0

50-1.88 (1.92- 50-2.51 (2.61- 50-2.42 (2.55- 50-2.37 (2.50-

Resolution (A)

1.88)^a 2.51)^a 2.42)^a 2.37)^a

-^merge 0.077 (0.785) 0.102 (0.643) 0.118 (1.017) 0.115 (1.104)

Ι/ σ (Ι) 15.2 (2.4) 12.1 (2.3) 15.4 (2.3) 25.9 (3.1)

Completeness (%) 97.6 (93.7) 94.6 (89.5) 100.0 (100.0) 100.0 (100.0)

Redundancy 5.8 (6.0) 3.8 (3.7) 9.4 (9.0) 9.1 (8.7)

Number of unique

19022 14320 17687 19048 reflections

Rwork/Rfree (%) 17.4/21.8 19.7/23.9 18.2/22.8 18.7/23.1

Number of non-H atoms

Protein 1499 2932 2920 2928

Water 137 55 71 58

Ligands(molecule) 1 2 2 2

Average B factors (A²)

Protein 38.68 68.70 56.51 68.13

Water 45.73 44.55 51.55 63.79 ligands 21.53 49.91 28.21 38.75

R.m.s. deviations

Bond lengths (A) 0.013 0.007 0.014 0.007

Bond angles (°) 1.580 1.262 1.613 1.203

Highest resolution shell (in A) shown in parentheses.

Example 16: DMXAA Activates Type I IFN and Proinflammatory Cytokine/Chemokine Production in mSTING-Deficient BMDCs reconstituted with hSTING Substitutions

[0328] Examples 1-8 show that c[G(2',5')pA(3',5')p] and its linkage analogs induce type

I IFN and proinflammatory cytokine/chemokine production in a STFNG-dependent manner in bone marrow-derived macrophages. To test whether various hSTFNG substitutions can rescue the deficiency of type I IFN and proinflammatory cytokine/chemokine production in response to DMXAA in mSTING-deficient bone marrow-derived dendritic cells (BMDCs), we generated BMDCs from homozygous functional null STFNG mice (Goldenticket, STING^Gt/Gt) (Sauer et al, 2011). Retroviruses carrying wt hSTING or hSTING mutants (hSTING⁰²³⁰¹, STING^sl62A/Q2661, hSTING^{sl62A/G230I/Q2661}, hSTING^sl62A) were used to transduce these BMDCs. Although wt hSTING did not induce the up-regulation of IFN-β mRNA after DMXAA treatment, we observed 2.6, 3.1, 4.2, and 2.2-fold increases in IFN-β mRNA levels in BMDCs expressing hSTING⁰²³⁰¹, hSTING^sl62A/Q2661, _hSTING^{sl62A/G230I/Q2661} and hSTING^sl62A, respectively. Similar to the results obtained from the luciferase reporter assays, we found that STFNG -derived BMDCs expressing hSTING^{sl62A/G230I/Q2661} had the highest IFN-β mRNA induction after DMXAA treatment, corroborating that G230I substitution and the pocket substitutions

S162A/Q226I lead to synergistic effects on hSTING sensitivity to DMXAA. We also observed up-regulation of CXCL10, CCL5 and IL-6 mRNAs in BMDCs expressing various hSTING mutants (Figure 18F), with hSTFNG^{sl62A G230I/Q2661} eliciting the strongest induction among the four mutants after DMXAA treatment. We also collected supernatants at 18 h post DMXAA treatment. At this time point, hSTFNG^{sl62A G230I/Q2661} induced the highest level of CXCL10 production compared with the other hSTING substituents (Figure 22E). We confirmed hSTING protein expression in transduced cells by Western blot analysis (Figure 18G).

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Table 6. DMXAA-hSTING^group complex REMARK T33: 0.1207 T12: -0.0135

REMARK T13: -0.0096 T23: -0.0277

REMARK L TENSOR

REMARK REMARK Ll l 4.8802 L22 3.2007

REMARK 3 REFINEMENT. REMARK L33 6.2531 L12 0.5545

REMARK 3 PROGRAM : PHENIX (phenix.refme: 1.8.2 1309) REMARK L13 -3.1583 L23 -0.6229

REMARK 3 AUTHORS : Adams,Afonine,Burnley,Chen,Davis,Echols,Gildea, REMARK S TENSOR

REMARK 3 : Gopal,Gros,Grosse-Kunstleve,Headd,Hung,Immormino, REMARK Sl l 0.0931 S12: -0.6224 S13: 0.0424

REMARK 3 : Ioerger,McCoy,McKee,Moriarty,Pai,Read,Richardson, REMARK S21 0.2192 S22: -0.0965 S23: -0.1503

REMARK 3 : Richardson,Romo,Sacchettini,Sauter,Smith,Storoni, REMARK S31 -0.0048 S32: 0.5314 S33: -0.0194

REMARK 3 : Terwilliger,Zwart REMARK TLS GROUP : 2

REMARK 3 REMARK SELECTION: chain Ά' and (resid 168 through 185 )

REMARK 3 REFINEMENT TARGET : ML REMARK ORIGIN FOR THE GROUP (A): - 32.7374 41.7922 9

REMARK 3 REMARK T TENSOR

REMARK 3 DATA USED IN REFINEMENT. REMARK Ti l 0.3021 T22 0.2444

REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.880 REMARK T33 0.3426 T12 -0.0595

REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 54.491 REMARK T13 0.0922 T23 -0.0478

REMARK 3 MIN(FOBS/SIGMA_FOBS) : 1.37 REMARK L TE] SOR

REMARK 3 COMPLETENESS FOR RANGE (%) : 96.91 REMARK Ll l 3.4374 L22 2.9964

REMARK 3 NUMBER OF REFLECTIONS : 19022 REMARK L33 3.1918 L12 2.4360

REMARK 3 NUMBER OF REFLECTIONS (NON-ANOMALOUS) : 19022 REMARK L13 1.3854 L23 2.0523

REMARK REMARK S TENSOR

REMARK 3 FLT TO DATA USED IN REFINEMENT. REMARK Sl l : 0.5743 S12: -1.1553 S13 0.5744

REMARK 3 R VALUE (WORKTNG + TEST SET) : 0.1765 REMARK S21 : 0.6347 S22: -0.7613 S23 0.8717

REMARK 3 R VALUE (WORKING SET) : 0.1743 REMARK S31 : 0.1473 S32: -0.3896 S33 0.0968

REMARK 3 FREE R VALUE : 0.2185 REMARK TLS GROUP : 3

REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.14 REMARK SELECTION: chain Ά' and (resid 186 through 211 )

REMARK 3 FREE R VALUE TEST SET COUNT : 977 REMARK ORIGIN FOR THE GROUP (A): - 27.1904 34.9528 -0

REMARK 3 REMARK T TENSOR

REMARK 3 FLT TO DATA USED IN REFINEMENT (IN BINS). REMARK Ti l 0.2543 T22 0.1132

REMARK 3 BIN RESOLUTION RANGE COMPL. NWORK NFREE RWORK REMARK T33 0.2799 T12 0.0289

RFREE REMARK T13 0.0152 T23 -0.0043

REMARK 1 54.5141 - 3.5962 0.98 2865 140 0.1574 0.1997 REMARK L TE]

REMARK 2 3.5962 - 2.8544 0.99 2698 112 0 1674 0.1953 REMARK Ll l 9.8039 L22: 4.3916

REMARK 3 2.8544 - 2.4936 0.98 2588 146 0 1813 0.2280 REMARK L33 2.9025 L12: 5.7740

REMARK 4 2.4936 - 2.2656 0.98 2537 160 0 1775 0.2272 REMARK L13 -3.0538 L23: -1.9563

REMARK 5 2.2656 - 2.1032 0.97 2507 144 0 1899 0.2259 REMARK 3 S TENSOR

REMARK 6 2.1032 - 1.9792 0.95 2455 131 0 2010 0.2427 REMARK 3 Sl l : -0.0078 S12: 0.1178 S13 0.0817

REMARK 7 1.9792 - 1.8801 0.93 2395 144 0 2943 0.3815 REMARK 3 S21 : -0.0786 S22: -0.0580 S23 0.0132

REMARK REMARK 3 S31 : 0.0919 S32: 0.0047 S33: -0.0013

REMARK 3 BULK SOLVENT MODELLING. REMARK 3 TLS GROUP : 4

REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL REMARK 3 SELECTION: chain Ά' and (resid 212 through 280 )

REMARK 3 SOLVENT RADIUS : 1.11 REMARK 3 ORIGIN FOR THE GROUP (A): - 25.5020 42.8838 -4

REMARK 3 SHRINKAGE RADIUS : 0.90 REMARK 3 T TENSOR

REMARK 3 GRID STEP FACTOR : 4.00 REMARK Ti l 0.2173 T22 0.1850

REMARK 3 REMARK T33 0.1792 T12 0.0218

REMARK 3 ERROR ESTIMATES. REMARK T13 -0.0241 T23: -0.0111

REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : 0.22 REMARK 3 L TENSOR

REMARK 3 PHASE ERROR (DEGREES, MAXIMUM- LIKELIHOOD BASED) : REMARK Ll l 2.6912 L22 1.9708

20.66 REMARK L33 1.7012 L12 0.7989

REMARK REMARK L13 -0.5883 L23 -0.0806

REMARK STRUCTURE FACTORS CALCULATION ALGORITHM : FFT REMARK S TENSOR

REMARK REMARK Sl l : 0.0125 S12: 0.0312 S13: 0.0124

REMARK DEVIATIONS FROM IDEAL VALUES. REMARK S21 : -0.0313 S22: -0.0579 S23: 0.1528

REMARK RMSD MAX COUNT REMARK S31 : 0.0124 S32: -0.1562 S33: 0.0446

REMARK BOND : 0.013 0.073 1551 REMARK TLS GROUP : 5

REMARK ANGLE : 1.580 11.179 2109 REMARK SELECTION: chain Ά' and (resid 281 through 299 )

REMARK CHIRALITY : 0.113 0.543 225 REMARK ORIGIN FOR THE GROUP (A): -7.1814 43.5461 -1

REMARK PLANARLTY : 0.007 0.049 281 REMARK T TENSOR

REMARK DIHEDRAL : 16.214 68.227 593 REMARK Ti l 0.1952 T22 0.1940

REMARK MIN NONBONDED DISTANCE : 1.748 REMARK T33 0.2378 T12 0.0443

REMARK REMARK T13 -0.0485 T23: -0.0102

REMARK MOLPROBLTY STATISTICS. REMARK L TE] SOR

REMARK ALL-ATOM CLASHSCORE : 4.68 REMARK Ll l 9.1414 L22 4.6808

REMARK RAMACHANDRAN PLOT: REMARK L33 6.3324 L12 1.0083

REMARK OUTLIERS : 0.00 % REMARK L13 -6.9440 L23 -0.5677

REMARK ALLOWED : 4.35 % REMARK S TENSOR

REMARK FAVORED : 95.65 % REMARK Sl l -0.1423 S12: -0.1738 S13: -0.4257

REMARK ROTAMER OUTLIERS : 3.07 % REMARK S21 0.0344 S22: 0.0534 S23: -0.4990

REMARK CBETA DEVIATIONS : 1 REMARK S31 0.5858 S32: 0.9638 S33: 0.2796

REMARK REMARK TLS GROUP : 6

REMARK ATOMIC DISPLACEMENT PARAMETERS. REMARK SELECTION: chain Ά' and (resid 300 through 314 )

REMARK WILSON B : 31.20 REMARK ORIGIN FOR THE GROUP (A): - 18.7157 39.1351 8.9537

REMARK RMS(B_ISO_OR_EQUrVALENT_BONDED) : 6.85 REMARK T TENSOR

REMARK ATOMS NUMBER OF ATOMS REMARK Ti l 0.4995 T22: 0.3964

REMARK ISO. ANISO. REMARK T33 0.2781 T12: 0.0221

REMARK ALL : 1650 1494 REMARK T13 -0.0514 T23: 0.0212

REMARK ALL (NO H) : 1650 1494 REMARK L TE] SOR

REMARK SOLVENT : 135 0 REMARK Ll l 4.8044 L22: 4.6243

REMARK NON-SOLVENT : 1515 1494 REMARK L33 3.0810 L12: -0.7724

REMARK HYDROGENS : 0 0 REMARK L13 -1.9557 L23: 3.4708

REMARK REMARK S TENSOR

REMARK TLS DETAILS. REMARK Sl l : -0.0010 S12: -0.9497 S13: -0.1092

REMARK NUMBER OF TLS GROUPS: 7 REMARK S21 : 1.1162 S22: 0.0813 S23: -0.3287

REMARK ORIGIN: CENTER OF MASS REMARK S31 : 0.4353 S32: -0.1031 S33: 0.1316

REMARK TLS GROUP : 1 REMARK TLS GROUP : 7

REMARK SELECTION: chain 'A' and (resid 154 through 167 ) REMARK SELECTION: chain Ά' and (resid 315 through 335 )

REMARK ORIGIN FOR THE GROUP (A): -13.4260 50.6427 4.3207 REMARK ORIGIN FOR THE GROUP (A): - 16.9164 28.0917 -5.816

REMARK T TENSOR REMARK T TENSOR

REMARK Ti l : 0.1683 T22: 0.1103 REMARK Ti l : 0.3475 T22: 0.3288

 ANISOU 83 C TYR A 163 3420 2401 2843 -131 67 -257 C ANISOU 128 O LEU A 168 3902 2857 2922 -451 424 -349 O

ATOM 84 O TYR A 163 ■19.100 49.451 4.884 1.00 22.77 o ATOM 129 N ARG A 169 -21.807 48.982 8.898 1.00 20.85 N

ANISOU 84 O TYR A 163 3407 2385 2859 -156 118 -251 o ANISOU 129 N ARG A 169 3373 2291 2260 -554 442 -509 N

ATOM 85 N TYR A 164 ■17.032 49.607 5.713 1.00 18.80 N ATOM 130 CA ARG A 169 -22.216 49.460 10.196 1.00 27.08 C

ANISOU 85 N TYR A 164 2912 2007 2223 -133 39 -237 N ANISOU 130 CA ARG A 169 4117 3204 2969 -735 648 -741 C

ATOM 86 CA TYR A 164 -17.478 49.264 7.064 1.00 17.85 C ATOM 131 CB ARG A 169 -21.316 50.632 10.607 1.00 31.16 C

ANISOU 86 CA TYR A 164 2817 1990 1975 -157 75 -204 c ANISOU 131 CB ARG A 169 4665 3783 3392 -877 719 -916 C

ATOM 87 CB TYR A 164 -16.284 48.963 7.957 1.00 18.02 c ATOM 132 CG ARG A 169 -21.420 50.911 12.029 1.00 57.57 C

ANISOU 87 CB TYR A 164 2810 2207 1829 -133 0 -129 c ANISOU 132 CG ARG A 169 7975 7349 6550 -1103 913 -1129 C

ATOM 88 CG TYR A 164 -16.714 48.809 9.406 1.00 23.37 c ATOM 133 CD ARG A 169 -20.118 51.483 12.519 1.00 58.51 C

ANISOU 88 CG TYR A 164 3523 3040 2316 -168 36 -100 c ANISOU 133 CD ARG A 169 8147 7661 6422 -1265 913 -1186 C

ATOM 89 CD1 TYR A 164 -17.613 47.812 9.783 1.00 27.45 c ATOM 134 NE ARG A 169 -20.103 52.913 12.341 1.00 57.53 N

ANISOU 89 CD1 TYR A 164 4115 3485 2829 -134 128 27 c ANISOU 134 NE ARG A 169 8006 7342 6512 -1281 997 -1396 N

ATOM 90 CE1 TYR A 164 -18.018 47.704 11.122 1.00 33.52 c ATOM 135 CZ ARG A 169 -19.256 53.726 12.961 1.00 59.53 C

ANISOU 90 CE1 TYR A 164 4928 4408 3401 -168 183 66 c ANISOU 135 CZ ARG A 169 8229 7721 6667 -1415 1034 -1459 C

ATOM 91 CZ TYR A 164 -17.504 48.597 12.056 1.00 39.32 c ATOM 136 NHl ARG A 169 -18.340 53.230 13.791 1.00 52.23 N

ANISOU 91 CZ TYR A 164 5635 5387 3919 -246 130 -50 c ANISOU 136 NHl ARG A 169 7280 7099 5465 -1536 981 -1345 N

ATOM 92 OH TYR A 164 -17.860 48.519 13.362 1.00 39.13 o ATOM 137 NH2 ARG A 169 -19.322 55.035 12.747 1.00 45.52 N

ANISOU 92 OH TYR A 164 5666 5548 3654 -291 187 -27 o ANISOU 137 ΝΉ2 ARG A 169 6446 5742 5109 -1409 1091 -1614 N

ATOM 93 CE2 TYR A 164 -16.619 49.576 11.700 1.00 32.31 c ATOM 138 C ARG A 169 ■23.674 49.912 10.190 1.00 32.27 C

ANISOU 93 CE2 TYR A 164 4674 4570 3034 -314 36 -208 c ANISOU 138 C ARG A 169 4672 3651 3938 -679 782 -940 C

ATOM 94 CD2 TYR A 164 -16.234 49.680 10.371 1.00 28.56 c ATOM 139 O ARG A 169 -24.351 49.890 11.224 1.00 30.74 O

ANISOU 94 CD2 TYR A 164 4152 3919 2781 -269 -3 -220 c ANISOU 139 O ARG A 169 4401 3589 3691 -823 968 -1129 O

ATOM 95 C TYR A 164 18.288 50.438 7.662 1.00 18.86 c ATOM 140 N LEU A 170 24.160 50.326 9.023 1.00 29.54 N

ANISOU 95 C TYR A 164 2950 2135 2080 -223 155 -347 c ANISOU 140 N LEU A 170 4317 2989 3917 -486 680 -913 N

ATOM 96 O TYR A 164 ■19.432 50.279 8.053 1.00 24.10 o ATOM 141 CA LEU A 170 -25.530 50.812 8.902 1.00 30.35 C

ANISOU 96 O TYR A 164 3621 2783 2752 -230 243 -341 o ANISOU 141 CA LEU A 170 4297 2856 4379 -390 756 -1118 C

ATOM 97 N ILE A 165 - 17.698 51.623 7.673 1.00 18.20 N ATOM 142 CB LEU A 170 -25.699 51.677 7.648 1.00 31.20 C

ANISOU 97 N FLE A 165 2866 2062 1987 -277 157 -481 N ANISOU 142 CB LEU A 170 4430 2642 4781 -201 558 -1045 C

ATOM 98 CA FLE A 165 -18.314 52.796 8.311 1.00 18.05 c ATOM 143 CG LEU A 170 -24.803 52.909 7.572 1.00 43.17 C

ANISOU 98 CA FLE A 165 2898 2010 1950 -335 289 -640 c ANISOU 143 CG LEU A 170 6037 4110 6257 -266 508 -1083 C

ATOM 99 CB ILE A 165 -17.304 53.978 8.362 1.00 20.17 c ATOM 144 CD1 LEU A 170 -25.163 53.707 6.324 1.00 42.70 C

ANISOU 99 CB FLE A 165 3160 2289 2213 -426 285 -760 c ANISOU 144 CD1 LEU A 170 6043 3818 6363 -103 255 -927 C

ATOM 100 CGI ILE A 165 -16.109 53.611 9.240 1.00 24.29 c ATOM 145 CD2 LEU A 170 -24.964 53.755 8.811 1.00 45.81 C

ANISOU 100 CGI FLE A 165 3654 3068 2507 -556 170 -805 c ANISOU 145 CD2 LEU A 170 6273 4542 6593 -396 709 -1381 C

ATOM 101 CD1 ILE A 165 -16.524 53.402 10.683 1.00 27.09 c ATOM 146 C LEU A 170 -26.486 49.654 8.789 1.00 30.84 C

ANISOU 101 CD1 FLE A 165 4048 3601 2642 -612 202 -840 c ANISOU 146 C LEU A 170 4281 2952 4483 -318 750 -1015 C

ATOM 102 CG2 ILE A 165 -17.941 55.281 8.938 1.00 22.09 c ATOM 147 O LEU A 170 -27.567 49.667 9.356 1.00 32.74 O

ANISOU 102 CG2 FLE A 165 3446 2450 2497 -445 441 -857 c ANISOU 147 O LEU A 170 4379 3206 4857 -355 906 -1234 O

ATOM 103 C FLE A 165 -19.561 53.238 7.533 1.00 21.76 c ATOM 148 N FLE A 171 -26.077 48.644 8.049 1.00 24.55 N

ANISOU 103 C FLE A 165 3353 2313 2603 -234 396 -623 c ANISOU 148 N FLE A 171 3571 2181 3578 -230 576 -706 N

ATOM 104 O FLE A 165 -20.594 53.601 8.128 1.00 23.47 o ATOM 149 CA FLE A 171 -27.024 47.620 7.594 1.00 27.28 C

ANISOU 104 O FLE A 165 3576 2516 2823 -207 534 -664 o ANISOU 149 CA ILE A 171 3860 2472 4034 -123 523 -585 C

ATOM 105 N GLY A 166 -19.460 53.210 6.215 1.00 20.23 N ATOM 150 CB FLE A 171 -26.692 47.227 6.136 1.00 23.98 C

ANISOU 105 N GLY A 166 3117 2029 2540 -167 337 -549 N ANISOU 150 CB FLE A 171 3522 1881 3706 64 285 -323 C

ATOM 106 CA GLY A 166 -20.499 53.788 5.360 1.00 19.98 c ATOM 151 CGI ILE A 171 -27.912 46.639 5.442 1.00 41.39 C

ANISOU 106 CA GLY A 166 3037 1904 2650 -51 410 -502 c ANISOU 151 CGI FLE A 171 5641 3956 6129 204 216 -269 C

ATOM 107 C GLY A 166 -21.514 52.776 4.821 1.00 24.12 c ATOM 152 CD1 ILE A 171 -28.780 47.742 4.831 1.00 42.71 C

ANISOU 107 C GLY A 166 3447 2512 3206 -17 351 -387 c ANISOU 152 CD1 FLE A 171 5731 4079 6417 290 140 -358 C

ATOM 108 O GLY A 166 -22.444 53.168 4.129 1.00 24.34 o ATOM 153 CG2 ILE A 171 -25.572 46.211 6.072 1.00 28.53 C

ANISOU 108 O GLY A 166 3375 2554 3318 79 380 -324 o ANISOU 153 CG2 FLE A 171 4204 2656 3982 35 173 -82 C

ATOM 109 N TYR A 167 -21.397 51.504 5.175 1.00 23.68 N ATOM 154 C FLE A 171 ■27.046 46.421 8.531 1.00 29.39 C

ANISOU 109 N TYR A 167 3396 2523 3077 -101 287 -352 N ANISOU 154 C FLE A 171 4145 3018 4005 -281 593 -494 C

ATOM 110 CA TYR A 167 -22.426 50.533 4.765 1.00 19.81 c ATOM 155 O FLE A 171 -28.076 45.781 8.758 1.00 27.90 O

ANISOU 110 CA TYR A 167 2816 2096 2616 -143 272 -288 c ANISOU 155 O FLE A 171 3878 2850 3872 -310 668 -525 O

ATOM 111 CB TYR A 167 -22.052 49.872 3.422 1.00 23.35 c ATOM 156 N LEU A 172 ■25.912 46.114 9.145 1.00 27.87 N

ANISOU 111 CB TYR A 167 3267 2518 3086 -176 164 -258 c ANISOU 156 N LEU A 172 4061 3046 3483 -409 561 -385 N

ATOM 112 CG TYR A 167 -23.121 48.879 2.961 1.00 23.88 c ATOM 157 CA LEU A 172 -25.867 44.907 9.974 1.00 26.16 C

ANISOU 112 CG TYR A 167 3247 2666 3161 -296 156 -245 c ANISOU 157 CA LEU A 172 3910 3056 2976 -563 555 -241 C

ATOM 113 CD1 TYR A 167 -24.425 49.308 2.704 1.00 19.55 c ATOM 158 CB LEU A 172 -24.426 44.468 10.243 1.00 22.14 C

ANISOU 113 CD1 TYR A 167 2505 2278 2646 -287 165 -226 c ANISOU 158 CB LEU A 172 3526 2717 2168 -608 395 -52 C

ATOM 114 CE1 TYR A 167 -25.424 48.411 2.321 1.00 22.32 c ATOM 159 CG LEU A 172 -23.609 44.006 9.042 1.00 28.10 C

ANISOU 114 CE1 TYR A 167 2733 2762 2987 -457 151 -240 c ANISOU 159 CG LEU A 172 4321 3362 2993 -386 156 157 C

ATOM 115 CZ TYR A 167 -25.105 47.061 2.165 1.00 24.77 c ATOM 160 CD1 LEU A 172 -22.179 43.700 9.507 1.00 25.83 C

ANISOU 115 CZ TYR A 167 3178 2967 3267 -649 163 -292 c ANISOU 160 CD1 LEU A 172 4105 3279 2430 -445 16 258 C

ATOM 116 OH TYR A 167 -26.079 46.168 1.785 1.00 20.89 o ATOM 161 CD2 LEU A 172 -24.218 42.787 8.379 1.00 31.53 C

ANISOU 116 OH TYR A 167 2588 2587 2763 -885 176 -349 o ANISOU 161 CD2 LEU A 172 4768 3685 3527 -258 30 350 C

ATOM 117 CE2 TYR A 167 -23.815 46.608 2.424 1.00 21.50 c ATOM 162 C LEU A 172 26.706 44.887 11.280 1.00 31.38 C

ANISOU 117 CE2 TYR A 167 2991 2339 2840 -605 186 -285 c ANISOU 162 C LEU A 172 4518 3905 3501 -830 793 -439 C

ATOM 118 CD2 TYR A 167 -22.832 47.524 2.818 1.00 22.85 c ATOM 163 O LEU A 172 ■27.306 43.832 11.605 1.00 30.65 O

ANISOU 118 CD2 TYR A 167 3220 2456 3008 -423 162 -252 c ANISOU 163 O LEU A 172 4456 3893 3297 -934 797 -327 O

ATOM 119 C TYR A 167 ■22.700 49.471 5.808 1.00 26.51 c ATOM 164 N PRO A 173 ■26.755 46.004 12.044 1.00 30.45 N

ANISOU 119 C TYR A 167 3702 2978 3391 -236 325 -262 c ANISOU 164 N PRO A 173 4326 3868 3376 -974 997 -743 N

ATOM 120 O TYR A 167 -23.812 49.378 6.349 1.00 21.01 o ATOM 165 CA PRO A 173 -27.489 45.944 13.322 1.00 30.58 C

ANISOU 120 O TYR A 167 2925 2356 2702 -269 419 -255 o ANISOU 165 CA PRO A 173 4285 4118 3216 -1278 1246 -963 C

ATOM 121 N LEU A 168 ■21.682 48.664 6.117 1.00 20.15 N ATOM 166 CB PRO A 173 -27.504 47.400 13.792 1.00 34.05 C

ANISOU 121 N LEU A 168 3350 1833 2474 -240 126 -203 N ANISOU 166 CB PRO A 173 4608 4557 3774 -1341 1448 -1346 C

ATOM 122 CA LEU A 168 -21.900 47.511 7.002 1.00 19.16 c ATOM 167 CG PRO A 173 -26.195 47.937 13.299 1.00 36.01 C

ANISOU 122 CA LEU A 168 3184 1907 2190 -260 151 -138 c ANISOU 167 CG PRO A 173 4964 4726 3994 -1214 1275 -1213 C

ATOM 123 CB LEU A 168 -20.650 46.651 7.142 1.00 22.03 c ATOM 168 CD PRO A 173 -26.014 47.266 11.913 1.00 28.01 C

ANISOU 123 CB LEU A 168 3570 2512 2289 -278 21 1 c ANISOU 168 CD PRO A 173 4008 3488 3145 -926 1012 -893 C

ATOM 124 CG LEU A 168 -20.227 46.018 5.808 1.00 24.77 c ATOM 169 C PRO A 173 28.915 45.448 13.222 1.00 37.33 C

ANISOU 124 CG LEU A 168 3919 2788 2703 -124 -156 158 c ANISOU 169 C PRO A 173 5010 4928 4245 -1293 1362 -1062 C

ATOM 125 CD1 LEU A 168 -18.963 45.224 6.058 1.00 25.63 c ATOM 170 O PRO A 173 ■29.357 44.789 14.159 1.00 41.16 O

ANISOU 125 CD1 LEU A 168 4007 3139 2591 -127 -287 228 c ANISOU 170 O PRO A 173 5523 5650 4468 -1584 1492 -1084 O

ATOM 126 CD2 LEU A 168 -21.337 45.096 5.188 1.00 22.93 c ATOM 171 N GLU A 174 -29.650 45.756 12.151 1.00 31.37 N

ANISOU 126 CD2 LEU A 168 3673 2390 2650 27 -217 288 c ANISOU 171 N GLU A 174 4120 3892 3906 -1020 1316 -1129 N

ATOM 127 C LEU A 168 22.399 47.929 8.363 1.00 22.35 c ATOM 172 CA GLU A 174 -31.053 45.322 12.137 1.00 35.66 C

ANISOU 127 C LEU A 168 3549 2418 2526 -419 346 -335 c ANISOU 172 CA GLU A 174 4502 4425 4622 -1053 1443 -1275 C

ATOM 128 O LEU A 168 ■23.295 47.323 8.944 1.00 25.48 o ATOM 173 CB GLU A 174 -32.016 46.487 11.920 1.00 47.44 C ANISOU 173 CB GLU A 174 5731 5744 6552 -922 1585 -1692 C ANISOU 218 CG2 FLE A 179 4286 3109 3682 -817 407 598 C

ATOM 174 CG GLU A 174 -31.962 47.512 13.043 1.00 52.98 C ATOM 219 C FLE A 179 35.768 37.559 8.954 1.00 33.00 C

ANISOU 174 CG GLU A 174 6333 6609 7187 -1133 1840 -2087 C ANISOU 219 C FLE A 179 4272 3772 4496 -1030 945 -113 C

ATOM 175 CD GLU A 174 -33.172 48.437 13.100 1.00 78.95 C ATOM 220 O FLE A 179 36.510 36.755 8.374 1.00 25.64 O

ANISOU 175 CD GLU A 174 9307 9786 10904 -1062 1944 -2481 C ANISOU 220 O FLE A 179 3307 2758 3677 -1004 893 -36 O

ATOM 176 OE1 GLU A 174 -33.548 49.025 12.056 1.00 77.51 O ATOM 221 N ARG A 180 -35.889 37.850 10.245 1.00 28.95 N

ANISOU 176 OE1 GLU A 174 9026 9295 11130 -744 1739 -2438 O ANISOU 221 N ARG A 180 3748 3516 3734 -1365 1180 -304 N

ATOM 177 OE2 GLU A 174 -33.748 48.583 14.208 1.00 96.52 O ATOM 222 CA ARG A 180 -36.908 37.212 11.055 1.00 31.42 C

ANISOU 177 OE2 GLU A 174 11394 12249 13032 -1344 2136 -2736 0 ANISOU 222 CA ARG A 180 4020 4047 3872 -1753 1401 -431 C

ATOM 178 C GLU A 174 ■31.328 44.214 11.152 1.00 30.54 C ATOM 223 CB ARG A 180 -36.792 37.742 12.471 1.00 34.30 c

ANISOU 178 C GLU A 174 3913 3634 4055 -883 1239 -960 C ANISOU 223 CB ARG A 180 4389 4716 3926 -2127 1657 -657 c

ATOM 179 O GLU A 174 -32.481 43.861 10.892 1.00 30.14 O ATOM 224 CG ARG A 180 -37.479 36.940 13.528 1.00 70.91 c

ANISOU 179 O GLU A 174 3720 3533 4199 -860 1304 -1059 O ANISOU 224 CG ARG A 180 9115 9608 8220 -2543 1773 -696 c

ATOM 180 N LEU A 175 30.260 43.653 10.597 1.00 26.19 N ATOM 225 CD ARG A 180 -36.682 37.111 14.819 1.00 77.83 c

ANISOU 180 N LEU A 175 3556 3031 3364 -766 993 -608 N ANISOU 225 CD ARG A 180 10196 10686 8689 -2768 1741 -672 c

ATOM 181 CA LEU A 175 -30.424 42.636 9.557 1.00 23.01 C ATOM 226 NE ARG A 180 -35.440 36.333 14.769 1.00 80.32 N

ANISOU 181 CA LEU A 175 3209 2474 3059 -583 786 -327 C ANISOU 226 NE ARG A 180 10839 10896 8783 -2704 1411 -205

ATOM 182 CB LEU A 175 -29.067 42.170 9.066 1.00 25.85 C ATOM 227 CZ ARG A 180 -34.258 36.749 15.214 1.00 78.79 C

ANISOU 182 CB LEU A 175 3753 2810 3260 -468 537 -18 C ANISOU 227 CZ ARG A 180 10774 10734 8427 -2671 1290 -107

ATOM 183 CG LEU A 175 -29.171 41.063 8.012 1.00 33.37 C ATOM 228 NH1 ARG A 180 -34.132 37.963 15.747 1.00 74.38 N

ANISOU 183 CG LEU A 175 4760 3616 4304 -291 327 245 C ANISOU 228 NH1 ARG A 180 10072 10310 7878 -2722 1489 -424

ATOM 184 CD1 LEU A 175 -29.764 41.625 6.726 1.00 29.74 C ATOM 229 NH2 ARG A 180 -33.201 35.942 15.121 1.00 78.07 N

ANISOU 184 CD1 LEU A 175 4179 2906 4216 -45 276 176 C ANISOU 229 ΝΉ2 ARG A 180 10929 10527 8206 -2559 950 277

ATOM 185 CD2 LEU A 175 -27.795 40.514 7.759 1.00 35.69 C ATOM 230 C ARG A 180 ■38.285 37.538 10.482 1.00 36.27 C

ANISOU 185 CD2 LEU A 175 5205 3940 4417 -217 104 488 C ANISOU 230 C ARG A 180 4292 4608 4880 -1646 1546 -759 C

ATOM 186 C LEU A 175 31.176 41.428 10.074 1.00 27.04 C ATOM 231 O ARG A 180 -39.166 36.679 10.371 1.00 33.43 o

ANISOU 186 C LEU A 175 3751 3116 3407 -785 843 -241 C ANISOU 231 O ARG A 180 3896 4287 4520 -1795 1592 -745 o

ATOM 187 O LEU A 175 32.043 40.857 9.392 1.00 29.08 O ATOM 232 N THR A 181 ■38.469 38.806 10.116 1.00 32.13 N

ANISOU 187 O LEU A 175 3939 3253 3858 -688 805 -200 O ANISOU 232 N THR A 181 3516 3982 4710 -1387 1598 -1064 N

ATOM 188 N GLN A 176 -30.817 40.996 11.276 1.00 32.36 N ATOM 233 CA THR A 181 -39.744 39.239 9.556 1.00 35.78 C

ANISOU 188 N GLN A 176 4555 4040 3702 -1092 915 -194 N ANISOU 233 CA THR A 181 3624 4365 5604 -1237 1687 -1404 C

ATOM 189 CA GLN A 176 -31.454 39.816 11.872 1.00 35.78 C ATOM 234 CB THR A 181 -39.755 40.754 9.341 1.00 42.70 C

ANISOU 189 CA GLN A 176 5076 4606 3914 -1358 954 -78 C ANISOU 234 CB THR A 181 4270 5103 6849 -967 1707 -1733 C

ATOM 190 CB GLN A 176 -30.847 39.578 13.243 1.00 42.72 C ATOM 235 OG1 THR A 181 -39.657 41.397 10.618 1.00 39.05 O

ANISOU 190 CB GLN A 176 6135 5759 4336 -1721 999 -16 C ANISOU 235 OG1 THR A 181 3741 4894 6200 -1247 1987 -2046

ATOM 191 CG GLN A 176 -31.457 38.427 13.985 1.00 67.24 C ATOM 236 CG2 THR A 181 -41.032 41.173 8.650 1.00 41.92 C

ANISOU 191 CG GLN A 176 9381 9015 7153 -2075 1034 116 C ANISOU 236 CG2 THR A 181 3810 4869 7250 -755 1715 -2055 C

ATOM 192 CD GLN A 176 -30.502 37.853 15.002 1.00 74.59 C ATOM 237 C THR A 181 39.999 38.515 8.224 1.00 34.84 C

ANISOU 192 CD GLN A 176 10517 10063 7760 -2195 791 308 C ANISOU 237 C THR A 181 3538 3999 5701 -968 1426 -1136 C

ATOM 193 OE1 GLN A 176 -30.917 37.196 15.953 1.00 73.42 O ATOM 238 O THR A 181 ■41.077 37.968 7.993 1.00 33.78 O

ANISOU 193 OE1 GLN A 176 10445 10043 7407 -2464 781 310 O ANISOU 238 O THR A 181 3242 3899 5696 -1037 1491 -1244 O

ATOM 194 NE2 GLN A 176 -29.205 38.093 14.802 1.00 83.07 N ATOM 239 N TYR A 182 ■38.983 38.485 7.376 1.00 28.75 N

ANISOU 194 NE2 GLN A 176 11665 11082 8818 -2001 587 451 N ANISOU 239 N TYR A 182 2972 3007 4943 -694 1143 -802 N

ATOM 195 C GLN A 176 ■32.983 39.967 11.980 1.00 35.25 C ATOM 240 CA TYR A 182 -39.100 37.790 6.088 1.00 32.60 C

ANISOU 195 C GLN A 176 4782 4576 4037 -1472 1211 -383 C ANISOU 240 CA TYR A 182 3512 3275 5597 -458 892 -545 C

ATOM 196 O GLN A 176 -33.768 39.034 11.713 1.00 36.10 O ATOM 241 CB TYR A 182 -37.766 37.890 5.372 1.00 27.90 C

ANISOU 196 O GLN A 176 4889 4653 4174 -1525 1195 -289 O ANISOU 241 CB TYR A 182 3149 2507 4946 -222 632 -232 C

ATOM 197 N ALA A 177 -33.409 41.148 12.419 1.00 33.69 N ATOM 242 CG TYR A 182 -37.732 37.200 4.022 1.00 26.03 C

ANISOU 197 N ALA A 177 4373 4453 3974 -1521 1453 -781 N ANISOU 242 CG TYR A 182 2981 2064 4845 4 377 21 C

ATOM 198 CA ALA A 177 -34.840 41.420 12.612 1.00 35.51 C ATOM 243 CD1 TYR A 182 -38.106 37.899 2.868 1.00 34.42 C

ANISOU 198 CA ALA A 177 4327 4746 4418 -1625 1715 -1162 C ANISOU 243 CD1 TYR A 182 3907 3020 6151 258 224 -44 C

ATOM 199 CB ALA A 177 -35.042 42.763 13.316 1.00 40.04 C ATOM 244 CE1 TYR A 182 -38.052 37.287 1.632 1.00 28.77 C

ANISOU 199 CB ALA A 177 4690 5428 5096 -1705 1974 -1628 C ANISOU 244 CE1 TYR A 182 3300 2446 5185 322 10 131 C

ATOM 200 C ALA A 177 ■35.577 41.396 11.264 1.00 36.04 C ATOM 245 CZ TYR A 182 -37.623 35.966 1.548 1.00 26.95 C

ANISOU 200 C ALA A 177 4230 4523 4940 -1269 1584 -1160 C ANISOU 245 CZ TYR A 182 3246 2262 4732 266 -48 321 C

ATOM 201 O ALA A 177 -36.722 40.937 11.165 1.00 32.93 O ATOM 246 OH TYR A 182 -37.569 35.346 0.309 1.00 30.13 O

ANISOU 201 O ALA A 177 3678 4161 4673 -1342 1688 -1292 O ANISOU 246 OH TYR A 182 3725 2806 4919 308 -162 363 O

ATOM 202 N ARG A 178 -34.922 41.903 10.226 1.00 33.09 N ATOM 247 CE2 TYR A 182 -37.249 35.254 2.681 1.00 26.36 C

ANISOU 202 N ARG A 178 3894 3882 4795 -912 1353 -1018 N ANISOU 247 CE2 TYR A 182 3294 2093 4630 105 40 458 C

ATOM 203 CA ARG A 178 -35.522 41.929 8.895 1.00 31.30 C ATOM 248 CD2 TYR A 182 -37.310 35.878 3.908 1.00 28.15 C

ANISOU 203 CA ARG A 178 3548 3376 4969 -587 1189 -984 C ANISOU 248 CD2 TYR A 182 3466 2338 4889 -76 262 321 C

ATOM 204 CB ARG A 178 -34.660 42.750 7.917 1.00 24.32 C ATOM 249 C TYR A 182 39.485 36.318 6.273 1.00 31.32 C

ANISOU 204 CB ARG A 178 2734 2235 4273 -273 964 -865 C ANISOU 249 C TYR A 182 3480 3209 5210 -700 903 -351 C

ATOM 205 CG ARG A 178 -34.729 44.226 8.210 1.00 29.40 C ATOM 250 O TYR A 182 ■40.404 35.777 5.626 1.00 28.21 O

ANISOU 205 CG ARG A 178 3226 2808 5136 -216 1072 -1210 C ANISOU 250 O TYR A 182 2964 2751 5002 -658 872 -374 O

ATOM 206 CD ARG A 178 -33.594 44.968 7.492 1.00 36.68 C ATOM 251 N ASN A 183 ■38.809 35.660 7.207 1.00 26.72 N

ANISOU 206 CD ARG A 178 4302 3535 6101 -19 865 -1043 C ANISOU 251 N ASN A 183 3153 2779 4221 -978 937 -161 N

ATOM 207 NE ARG A 178 -33.780 44.953 6.045 1.00 32.58 N ATOM 252 CA ASN A 183 -39.072 34.248 7.446 1.00 27.59 C

ANISOU 207 NE ARG A 178 3797 2827 5754 232 575 -811 N ANISOU 252 CA ASN A 183 3447 2942 4094 -1235 907 63 C

ATOM 208 CZ ARG A 178 -32.785 44.927 5.164 1.00 32.73 C ATOM 253 CB ASN A 183 -37.931 33.627 8.220 1.00 29.61 C

ANISOU 208 CZ ARG A 178 4012 2847 5577 323 340 -503 C ANISOU 253 CB ASN A 183 4050 3258 3943 -1420 798 369 C

ATOM 209 NH1 ARG A 178 -31.534 44.928 5.602 1.00 31.02 N ATOM 254 CG ASN A 183 -36.733 33.420 7.346 1.00 29.71 C

ANISOU 209 NH1 ARG A 178 3951 2630 5206 260 376 -438 N ANISOU 254 CG ASN A 183 4233 3046 4009 -1084 482 667 C

ATOM 210 NH2 ARG A 178 -33.045 44.914 3.848 1.00 28.33 N ATOM 255 OD1 ASN A 183 -36.901 33.319 6.147 1.00 28.72 O

ANISOU 210 NH2 ARG A 178 3507 2332 4927 427 123 -318 N ANISOU 255 OD1 ASN A 183 4027 2729 4158 -799 344 710 O

ATOM 211 C ARG A 178 -35.662 40.522 8.387 1.00 30.06 C ATOM 256 ND2 ASN A 183 -35.528 33.372 7.916 1.00 27.65 N

ANISOU 211 C ARG A 178 3523 3198 4701 -598 1045 -659 C ANISOU 256 ND2 ASN A 183 4190 2823 3492 -1123 366 849 N

ATOM 212 O ARG A 178 -36.644 40.166 7.756 1.00 33.78 O ATOM 257 C ASN A 183 40.419 33.884 8.058 1.00 41.63 C

ANISOU 212 O ARG A 178 3854 3576 5407 -511 1026 -707 O ANISOU 257 C ASN A 183 5059 4924 5836 -1582 1173 -185 C

ATOM 213 N FLE A 179 34.654 39.710 8.661 1.00 24.53 N ATOM 258 O ASN A 183 ■40.760 32.687 8.225 1.00 33.33 O

ANISOU 213 N FLE A 179 3091 2575 3654 -699 922 -335 N ANISOU 258 O ASN A 183 4166 3906 4591 -1835 1153 -4 O

ATOM 214 CA FLE A 179 -34.688 38.327 8.216 1.00 25.44 C ATOM 259 N GLN A 184 ■41.218 34.891 8.374 1.00 33.78 N

ANISOU 214 CA ILE A 179 3356 2641 3668 -707 758 -23 C ANISOU 259 N GLN A 184 3734 4060 5042 -1607 1419 -621 N

ATOM 215 CB FLE A 179 -33.300 37.686 8.390 1.00 29.09 C ATOM 260 CA GLN A 184 -42.591 34.608 8.785 1.00 36.01 C

ANISOU 215 CB FLE A 179 4101 3124 3829 -719 552 312 C ANISOU 260 CA GLN A 184 3776 4545 5359 -1903 1681 -931 C

ATOM 216 CGI ILE A 179 -32.378 38.220 7.289 1.00 27.69 C ATOM 261 CB GLN A 184 -43.284 35.867 9.291 1.00 58.73 C

ANISOU 216 CGI FLE A 179 3936 2757 3828 -381 349 408 C ANISOU 261 CB GLN A 184 6273 7583 8460 -1910 1951 -1472 C

ATOM 217 CD1 ILE A 179 -30.955 37.759 7.426 1.00 29.97 C ATOM 262 CG GLN A 184 -42.728 36.349 10.615 1.00 60.83 C

ANISOU 217 CD1 FLE A 179 4433 3081 3872 -361 154 658 C ANISOU 262 CG GLN A 184 6683 8078 8352 -2147 2095 -1570 C

ATOM 218 CG2 ILE A 179 -33.384 36.176 8.333 1.00 29.16 C ATOM 263 CD GLN A 184 -43.342 37.664 11.059 1.00 84.00 C







 ANISOU 628 CA ASN A 229 4905 4902 5746 371 999 -1183 C ANISOU 673 CB FLE A 235 8305 6810 8659 209 920 -1381

ATOM 629 CB ASN A 229 36.103 53.468 7.094 1.00 50.46 C ATOM 674 CGI ILE A 235 -27.630 58.225 6.340 1.00 54.36

ANISOU 629 CB ASN A 229 5978 6073 7123 438 1170 -1302 C ANISOU 674 CGI FLE A 235 7256 6002 7397 125 892 -1398

ATOM 630 CG ASN A 229 37.184 53.342 6.034 1.00 69.56 C ATOM 675 CD1 ILE A 235 -26.913 57.078 5.675 1.00 60.49

ANISOU 630 CG ASN A 229 8221 8471 9738 575 1102 -1193 C ANISOU 675 CD1 FLE A 235 8037 6912 8034 107 718 -1217

ATOM 631 OD1 ASN A 229 -37.415 54.274 5.258 1.00 85.07 O ATOM 676 CG2 ILE A 235 -26.040 59.676 5.099 1.00 61.11

ANISOU 631 OD1 ASN A 229 10121 10301 11901 713 1074 -1153 O ANISOU 676 CG2 FLE A 235 8200 6613 8405 126 819 -1314

ATOM 632 ND2 ASN A 229 -37.831 52.178 5.973 1.00 71.20 N ATOM 677 C FLE A 235 29.397 60.734 6.767 1.00 61.97

ANISOU 632 ND2 ASN A 229 8350 8812 9891 530 1065 -1134 N ANISOU 677 C FLE A 235 8151 6559 8836 297 1241 -1675

ATOM 633 C ASN A 229 -33.639 53.364 7.518 1.00 45.38 C ATOM 678 O FLE A 235 ■29.803 60.244 7.835 1.00 56.45

ANISOU 633 C ASN A 229 5620 5459 6162 261 1047 -1287 C ANISOU 678 O FLE A 235 7449 5997 8002 216 1326 -1808

ATOM 634 O ASN A 229 -33.495 52.917 8.663 1.00 39.60 O ATOM 679 N LYS A 236 -30.179 61.389 5.933 1.00 58.00

ANISOU 634 O ASN A 229 4948 4844 5254 131 1124 -1369 O ANISOU 679 N LYS A 236 7566 5879 8592 470 1265 -1595

ATOM 635 N FLE A 230 ■32.832 54.270 6.985 1.00 35.87 N ATOM 680 CA LYS A 236 -31.563 61.560 6.253 1.00 56.87

ANISOU 635 N FLE A 230 4477 4127 5025 303 999 -1277 N ANISOU 680 CA LYS A 236 7306 5728 8575 569 1364 -1633

ATOM 636 CA FLE A 230 -31.712 54.814 7.738 1.00 28.23 C ATOM 681 CB LYS A 236 -31.974 63.015 6.093 1.00 56.19

ANISOU 636 CA ILE A 230 3642 3148 3934 191 1032 -1380 C ANISOU 681 CB LYS A 236 7195 5435 8719 657 1437 -1634

ATOM 637 CB FLE A 230 -30.396 54.600 7.004 1.00 31.07 C ATOM 682 CG LYS A 236 -31.412 63.913 7.172 1.00 66.81

ANISOU 637 CB FLE A 230 4084 3504 4218 167 865 -1252 C ANISOU 682 CG LYS A 236 8641 6733 10010 516 1554 -1825

ATOM 638 CGI ILE A 230 -30.119 53.114 6.857 1.00 34.74 C ATOM 683 CD LYS A 236 -32.445 64.920 7.609 1.00 70.51

ANISOU 638 CGI FLE A 230 4553 4123 4523 115 744 -1116 C ANISOU 683 CD LYS A 236 9039 7080 10671 592 1698 -1908

ATOM 639 CD1 ILE A 230 -29.810 52.457 8.205 1.00 42.86 C ATOM 684 CE LYS A 236 -32.283 66.237 6.878 1.00 73.71

ANISOU 639 CD1 FLE A 230 5646 5307 5332 -35 789 -1181 C ANISOU 684 CE LYS A 236 9457 7242 11306 682 1699 -1830

ATOM 640 CG2 ILE A 230 -29.234 55.274 7.782 1.00 32.30 C ATOM 685 NZ LYS A 236 -31.008 66.973 7.199 1.00 60.28

ANISOU 640 CG2 FLE A 230 4358 3649 4263 44 897 -1367 C ANISOU 685 NZ LYS A 236 7897 5465 9544 534 1715 -1921

ATOM 641 C FLE A 230 31.911 56.298 7.931 1.00 39.52 C ATOM 686 C LYS A 236 - -32.347 60.673 5.320 1.00 51.03

ANISOU 641 C FLE A 230 5074 4402 5540 244 1169 -1529 C ANISOU 686 C LYS A 236 6441 5053 7894 702 1264 -1462

ATOM 642 O FLE A 230 ■32.109 57.030 6.965 1.0040.28 O ATOM 687 O LYS A 236 -32.147 60.702 4.102 1.00 66.07

ANISOU 642 O FLE A 230 5122 4340 5844 376 1140 -1463 O ANISOU 687 O LYS A 236 8328 6909 9867 789 1122 -1262

ATOM 643 N ASP A 231 -31.871 56.734 9.191 1.00 38.78 N ATOM 688 N ASN A 237 -33.181 59.844 5.925 1.00 43.83

ANISOU 643 N ASP A 231 5039 4335 5361 135 1322 -1729 N ANISOU 688 N ASN A 237 5451 4297 6903 684 1312 -1515

ATOM 644 CA ASP A 231 -31.930 58.145 9.521 1.00 38.69 C ATOM 689 CA ASN A 237 -34.173 59.071 5.221 1.00 50.87

ANISOU 644 CA ASP A 231 5051 4145 5504 157 1474 -1907 C ANISOU 689 CA ASN A 237 6199 5278 7850 791 1226 -1366

ATOM 645 CB ASP A 231 -33.361 58.538 9.906 1.00 43.76 C ATOM 690 CB ASN A 237 -35.370 59.956 4.951 1.00 62.08

ANISOU 645 CB ASP A 231 5574 4744 6308 243 1632 -1990 C ANISOU 690 CB ASN A 237 7474 6546 9569 964 1320 -1370

ATOM 646 CG ASP A 231 -33.661 59.998 9.592 1.00 76.54 C ATOM 691 CG ASN A 237 -35.874 60.609 6.213 1.00 76.21

ANISOU 646 CG ASP A 231 9695 8673 10713 351 1690 -2012 C ANISOU 691 CG ASN A 237 9270 8322 11366 905 1503 -1558

ATOM 647 OD2 ASP A 231 -33.685 60.837 10.532 1.00 86.05 O ATOM 692 OD1 ASN A 237 -36.404 59.932 7.102 1.00 81.73

ANISOU 647 OD2 ASP A 231 10945 9842 11908 275 1809 -2160 O ANISOU 692 OD1 ASN A 237 9933 9167 11954 830 1594 -1667

ATOM 648 OD1 ASP A 231 -33.874 60.301 8.395 1.00 88.58 O ATOM 693 ND2 ASN A 237 -35.673 61.923 6.330 1.00 77.96

ANISOU 648 OD1 ASP A 231 11151 10063 12444 508 1611 -1872 O ANISOU 693 ND2 ASN A 237 9543 8369 11707 925 1564 -1602

ATOM 649 C ASP A 231 ■ -30.962 58.462 10.669 1.00 54.88 C ATOM 694 C ASN A 237 33.667 58.433 3.944 1.00 48.25

ANISOU 649 C ASP A 231 7238 6268 7344 -35 1516 -2056 C ANISOU 694 C ASN A 237 5877 5005 7451 817 1004 -1135

ATOM 650 O ASP A 231 -31.382 58.798 11.778 1.00 54.06 O ATOM 695 O ASN A 237 34.087 58.754 2.835 1.00 58.60

ANISOU 650 O ASP A 231 7143 6220 7178 -115 1635 -2184 O ANISOU 695 O ASN A 237 7108 6238 8920 953 918 -982

ATOM 651 N ARG A 232 -29.666 58.360 10.385 1.00 50.25 N ATOM 696 N ARG A 238 -32.727 57.533 4.101 1.00 29.46

ANISOU 651 N ARG A 232 6745 5701 6647 -112 1388 -2001 N ANISOU 696 N ARG A 238 3599 2766 4829 683 916 -1110

ATOM 652 CA ARG A 232 -28.629 58.666 11.356 1.00 50.55 C ATOM 697 CA ARG A 238 -32.293 56.720 3.001 1.00 27.71

ANISOU 652 CA ARG A 232 6896 5823 6489 -297 1385 -2109 C ANISOU 697 CA ARG A 238 3383 2621 4525 694 728 -918

ATOM 653 CB ARG A 232 -28.513 57.552 12.393 1.00 53.95 C ATOM 698 CB ARG A 238 -30.811 56.514 3.080 1.00 31.28

ANISOU 653 CB ARG A 232 7362 6514 6625 -442 1364 -2117 C ANISOU 698 CB ARG A 238 3978 3100 4806 575 665 -911

ATOM 654 CG ARG A 232 -27.882 56.281 11.846 1.00 52.47 C ATOM 699 CG ARG A 238 -30.119 56.413 1.754 1.00 45.66

ANISOU 654 CG ARG A 232 7174 6457 6307 -446 1173 -1903 C ANISOU 699 CG ARG A 238 5823 4933 6593 603 504 -729

ATOM 655 CD ARG A 232 -27.772 55.238 12.950 1.00 59.29 C ATOM 700 CD ARG A 238 -28.621 56.449 1.919 1.00 35.81

ANISOU 655 CD ARG A 232 8077 7565 6887 -591 1157 -1893 C ANISOU 700 CD ARG A 238 4700 3689 5218 492 470 -740

ATOM 656 NE ARG A 232 -27.302 53.946 12.452 1.00 63.91 N ATOM 701 NE ARG A 238 -28.039 57.711 1.553 1.00 33.42

ANISOU 656 NE ARG A 232 8643 8256 7383 -573 977 -1658 N ANISOU 701 NE ARG A 238 4448 3209 5042 517 505 -745

ATOM 657 CZ ARG A 232 -28.103 53.016 11.939 1.00 63.07 C ATOM 702 CZ ARG A 238 -26.761 57.864 1.284 1.00 33.74

ANISOU 657 CZ ARG A 232 8463 8166 7335 -480 952 -1524 C ANISOU 702 CZ ARG A 238 4574 3234 5011 440 456 -713

ATOM 658 NH1 ARG A 232 -29.412 53.247 11.854 1.00 60.46 N ATOM 703 NH1 ARG A 238 -26.296 59.022 0.941 1.00 36.08

ANISOU 658 NH1 ARG A 232 8055 7768 7148 -396 1084 -1593 N ANISOU 703 NH1 ARG A 238 4917 3362 5430 451 491 -707

ATOM 659 ΝΉ2 ARG A 232 ■27.600 51.855 11.516 1.00 54.53 N ATOM 704 ΝΉ2 ARG A 238 -25.959 56.855 1.380 1.00 24.24

ANISOU 659 ΝΉ2 ARG A 232 7375 7162 6180 -474 800 -1329 N ANISOU 704 ΝΉ2 ARG A 238 3402 2182 3625 352 376 -682

ATOM 660 C ARG A 232 -27.309 58.791 10.610 1.00 49.47 C ATOM 705 C ARG A 238 32.979 55.392 3.149 1.00 32.56

ANISOU 660 C ARG A 232 6820 5636 6340 -325 1241 -2022 C ANISOU 705 C ARG A 238 3925 3416 5031 660 692 -891

ATOM 661 O ARG A 232 -27.249 58.510 9.396 1.0041.11 O ATOM 706 O ARG A 238 -33.285 55.012 4.227 1.00 34.10

ANISOU 661 O ARG A 232 5711 4514 5394 -201 1120 -1826 O ANISOU 706 O ARG A 238 4116 3692 5150 584 801 -1016

ATOM 662 N ALA A 233 -26.255 59.173 11.342 1.00 48.73 N ATOM 707 N VAL A 239 33.214 54.691 2.059 1.00 27.39

ANISOU 662 N ALA A 233 6811 5606 6098 -489 1217 -2109 N ANISOU 707 N VAL A 239 3213 2825 4369 708 549 -735

ATOM 663 CA ALA A 233 -24.918 59.411 10.776 1.00 52.66 C ATOM 708 CA VAL A 239 -33.847 53.382 2.169 1.00 27.65

ANISOU 663 CA ALA A 233 7362 6063 6583 -546 1098 -2057 C ANISOU 708 CA VAL A 239 3180 3014 4311 662 515 -713

ATOM 664 CB ALA A 233 -24.276 58.097 10.260 1.00 43.91 C ATOM 709 CB VAL A 239 -35.220 53.338 1.521 1.00 36.43

ANISOU 664 CB ALA A 233 6226 5120 5337 -537 898 -1821 C ANISOU 709 CB VAL A 239 4120 4141 5582 770 489 -653

ATOM 665 C ALA A 233 -24.964 60.438 9.651 1.00 44.36 C ATOM 710 CGI VAL A 239 -35.798 51.929 1.653 1.00 38.27

ANISOU 665 C ALA A 233 6294 4747 5816 -416 1122 -2016 C ANISOU 710 CGI VAL A 239 4293 4532 5715 695 458 -640

ATOM 666 O ALA A 233 -24.316 60.263 8.615 1.00 39.12 O ATOM 711 CG2 VAL A 239 -36.140 54.349 2.152 1.00 33.68

ANISOU 666 O ALA A 233 5616 4048 5200 -363 989 -1837 O ANISOU 711 CG2 VAL A 239 3674 3698 5427 855 643 -759

ATOM 667 N GLY A 234 -25.761 61.480 9.847 1.00 50.75 N ATOM 712 C VAL A 239 32.944 52.388 1.482 1.00 28.59

ANISOU 667 N GLY A 234 7075 5404 6802 -349 1254 -2099 N ANISOU 712 C VAL A 239 3378 3215 4272 598 372 -603

ATOM 668 CA GLY A 234 -25.818 62.564 8.894 1.00 52.66 C ATOM 713 O VAL A 239 32.579 52.590 0.325 1.00 27.41

ANISOU 668 CA GLY A 234 7304 5394 7310 -233 1278 -2045 C ANISOU 713 O VAL A 239 3240 3027 4149 652 262 -490

ATOM 669 C GLY A 234 -26.695 62.270 7.696 1.00 55.43 C ATOM 714 N TYR A 240 32.538 51.330 2.207 1.00 22.82

ANISOU 669 C GLY A 234 7572 5640 7851 -26 1252 -1886 C ANISOU 714 N TYR A 240 2703 2590 3376 482 380 -633

ATOM 670 O GLY A 234 -27.012 63.172 6.925 1.00 58.34 O ATOM 715 CA TYR A 240 -31.687 50.296 1.614 1.00 23.45

ANISOU 670 O GLY A 234 7911 5806 8449 95 1274 -1812 O ANISOU 715 CA TYR A 240 2850 2734 3326 427 261 -538

ATOM 671 N FLE A 235 ■27.100 61.019 7.517 1.0046.88 N ATOM 716 CB TYR A 240 -30.488 49.964 2.512 1.00 23.75

ANISOU 671 N FLE A 235 6438 4717 6659 14 1178 -1789 N ANISOU 716 CB TYR A 240 3005 2810 3210 319 279 -573

ATOM 672 CA FLE A 235 -27.937 60.738 6.363 1.00 56.75 C ATOM 717 CG TYR A 240 -29.448 51.069 2.615 1.00 25.40

ANISOU 672 CA ILE A 235 7588 5912 8064 200 1113 -1597 C ANISOU 717 CG TYR A 240 3294 2933 3422 315 291 -607

ATOM 673 CB FLE A 235 -27.490 59.504 5.548 1.00 62.57 C ATOM 718 CD1 TYR A 240 -29.650 52.174 3.463 1.00 34.26 ANISOU 718 CD1 TYR A 240 4425 3990 4601 311 409 -733 C ANISOU 763 C TYR A 245 3124 2734 3210 -376 -22 -325 C

ATOM 719 CE1 TYR A 240 -28.689 53.181 3.548 1.00 34.44 C ATOM 764 O TYR A 245 -31.168 32.475 -2.244 1.00 24.04 O

ANISOU 719 CE1 TYR A 240 4524 3926 4636 290 424 -775 C ANISOU 764 O TYR A 245 3178 2704 3251 -377 33 -238 O

ATOM 720 CZ TYR A 240 -27.524 53.079 2.760 1.00 28.77 C ATOM 765 N GLU A 246 -31.907 31.984 -4.328 1.00 22.81 N

ANISOU 720 CZ TYR A 240 3862 3196 3873 277 318 -678 C ANISOU 765 N GLU A 246 2986 2567 3114 -457 -26 -417 N

ATOM 721 OH TYR A 240 -26.537 54.046 2.799 1.00 29.68 O ATOM 766 CA GLU A 246 -31.921 30.529 -4.156 1.00 22.71 C

ANISOU 721 OH TYR A 240 4044 3228 4004 242 331 -714 O ANISOU 766 CA GLU A 246 3018 2415 3194 -544 47 -430 C

ATOM 722 CE2 TYR A 240 -27.317 52.004 1.941 1.00 29.65 C ATOM 767 CB GLU A 246 -33.196 29.909 -4.772 1.00 23.99 C

ANISOU 722 CE2 TYR A 240 3961 3378 3927 289 212 -557 C ANISOU 767 CB GLU A 246 3115 2606 3396 -679 41 -541 C

ATOM 723 CD2 TYR A 240 -28.284 50.998 1.872 1.00 24.89 C ATOM 768 CG GLU A 246 -34.442 30.468 -4.113 1.00 31.00 C

ANISOU 723 CD2 TYR A 240 3294 2852 3313 307 199 -527 C ANISOU 768 CG GLU A 246 3887 3613 4280 -715 30 -519 C

ATOM 724 C TYR A 240 -32.477 49.011 1.412 1.00 26.68 C ATOM 769 CD GLU A 246 -35.755 29.880 -4.614 1.0049.61 C

ANISOU 724 C TYR A 240 3189 3243 3707 398 225 -499 C ANISOU 769 CD GLU A 246 6150 6014 6685 -857 19 -620 C

ATOM 725 O TYR A 240 -33.433 48.739 2.144 1.00 25.18 O ATOM 770 OE1 GLU A 246 -36.740 29.963 -3.839 1.00 47.07 O

ANISOU 725 O TYR A 240 2926 3100 3542 376 309 -559 O ANISOU 770 OE1 GLU A 246 5735 5749 6401 -907 52 -592 O

ATOM 726 N SERA 241 ■32.025 48.196 0.460 1.00 27.20 N ATOM 771 OE2 GLU A 246 -35.800 29.347 -5.750 1.00 51.49 O

ANISOU 726 N SER A 241 3281 3339 3716 385 112 -409 N ANISOU 771 OE2 GLU A 246 6403 6239 6921 -926 -16 -731 O

ATOM 727 CA SER A 241 -32.653 46.911 0.177 1.00 30.58 C ATOM 772 C GLU A 246 -30.689 29.934 -4.807 1.00 28.55 C

ANISOU 727 CA SER A 241 3658 3846 4117 341 74 -380 C ANISOU 772 C GLU A 246 3851 3036 3961 -504 71 -452 C

ATOM 728 CB SER A 241 -33.281 46.920 -1.212 1.00 31.87 C ATOM 773 O GLU A 246 -30.278 30.363 -5.898 1.00 27.96 O

ANISOU 728 CB SER A 241 3740 4020 4350 403 -28 -316 C ANISOU 773 O GLU A 246 3791 3007 3826 -471 26 -526 O

ATOM 729 OG SER A 241 -34.199 47.985 -1.336 1.00 51.40 O ATOM 774 N LEU A 247 ■30.102 28.930 -4.149 1.00 23.76 N

ANISOU 729 OG SER A 241 6108 6462 6961 496 -7 -323 O ANISOU 774 N LEU A 247 3304 2274 3450 -505 146 -384 N

ATOM 730 C SER A 241 ■ 31.619 45.814 0.181 1.00 29.71 C ATOM 775 CA LEU A 247 -28.939 28.242 -4.686 1.00 24.67 C

ANISOU 730 C SER A 241 3645 3759 3884 264 31 -341 C ANISOU 775 CA LEU A 247 3494 2249 3630 -458 189 -403 C

ATOM 731 O SERA 241 ■30.433 46.081 -0.060 1.00 26.33 O ATOM 776 CB LEU A 247 -27.834 28.146 -3.644 1.00 24.44 C

ANISOU 731 O SER A 241 3303 3294 3406 268 -4 -312 O ANISOU 776 CB LEU A 247 3500 2143 3643 -360 214 -241 C

ATOM 732 N ASN A 242 -32.060 44.570 0.404 1.00 21.69 N ATOM 777 CG LEU A 247 -27.530 29.467 -2.968 1.00 32.33 C

ANISOU 732 N ASN A 242 2610 2795 2837 196 38 -335 N ANISOU 777 CG LEU A 247 4468 3289 4527 -282 148 -151 C

ATOM 733 CA ASN A 242 -31.138 43.438 0.208 1.00 20.43 C ATOM 778 CD1 LEU A 247 -26.464 29.230 -1.971 1.00 41.08 C

ANISOU 733 CA ASN A 242 2531 2634 2596 141 -6 -285 C ANISOU 778 CD1 LEU A 247 5605 4332 5671 -209 161 4 C

ATOM 734 CB ASN A 242 -30.545 42.938 1.522 1.00 25.55 C ATOM 779 CD2 LEU A 247 -27.029 30.420 -4.025 1.00 35.98 C

ANISOU 734 CB ASN A 242 3247 3300 3161 70 53 -279 C ANISOU 779 CD2 LEU A 247 4924 3839 4909 -222 96 -232 C

ATOM 735 CG ASN A 242 -29.729 43.996 2.224 1.00 34.55 C ATOM 780 C LEU A 247 ■29.392 26.842 -5.050 1.00 32.38 C

ANISOU 735 CG ASN A 242 4443 4431 4256 82 80 -306 C ANISOU 780 C LEU A 247 4501 3073 4729 -569 265 -489 C

ATOM 736 OD1 ASN A 242 -30.267 44.771 3.008 1.00 31.48 O ATOM 781 O LEU A 247 ■29.989 26.149 -4.228 1.00 31.07 O

ANISOU 736 OD1 ASN A 242 4028 4056 3875 79 157 -374 O ANISOU 781 O LEU A 247 4330 2834 4641 -639 312 -427 O

ATOM 737 ND2 ASN A 242 -28.420 44.060 1.920 1.00 25.65 N ATOM 782 N LEU A 248 ■29.106 26.418 -6.286 1.00 25.92 N

ANISOU 737 ND2 ASN A 242 3385 3277 3086 91 23 -264 N ANISOU 782 N LEU A 248 3719 2205 3925 -597 287 -638 N

ATOM 738 C ASN A 242 -31.906 42.336 -0.462 1.00 26.18 C ATOM 783 CA LEU A 248 -29.552 25.102 -6.744 1.00 27.72 C

ANISOU 738 C ASN A 242 3206 3388 3353 103 -40 -275 C ANISOU 783 CA LEU A 248 3981 2280 4271 -719 367 -758 C

ATOM 739 O ASN A 242 -33.114 42.207 -0.253 1.00 25.14 O ATOM 784 CB LEU A 248 -30.257 25.192 -8.098 1.00 31.09 C

ANISOU 739 O ASN A 242 2979 3296 3277 85 -6 -306 O ANISOU 784 CB LEU A 248 4391 2814 4607 -831 326 -962 C

ATOM 740 N SERA 243 ■31.193 41.563 -1.282 1.00 20.70 N ATOM 785 CG LEU A 248 -31.263 26.318 -8.311 1.00 47.71 C

ANISOU 740 N SER A 243 2568 2671 2627 87 -100 -241 N ANISOU 785 CG LEU A 248 6402 5163 6562 -862 203 -970 C

ATOM 741 CA SER A 243 -31.815 40.594 -2.141 1.00 27.51 C ATOM 786 CD1 LEU A 248 -31.783 26.218 -9.732 1.00 48.11 C

ANISOU 741 CA SER A 243 3391 3549 3513 45 -140 -251 C ANISOU 786 CD1 LEU A 248 6447 5309 6525 -976 158 -1163 C

ATOM 742 CB SER A 243 -31.215 40.694 -3.538 1.00 29.13 C ATOM 787 CD2 LEU A 248 -32.417 26.193 -7.325 1.00 40.52 C

ANISOU 742 CB SER A 243 3632 3745 3691 77 -222 -240 C ANISOU 787 CD2 LEU A 248 5415 4278 5701 -937 199 -900 C

ATOM 743 OG SER A 243 -31.640 41.898 -4.131 1.00 30.14 O ATOM 788 C LEU A 248 ■28.361 24.168 -6.905 1.00 33.33 C

ANISOU 743 OG SER A 243 3705 3903 3842 147 -270 -229 O ANISOU 788 C LEU A 248 4770 2770 5122 -656 470 -761 C

ATOM 744 C SER A 243 ■ 31.632 39.181 -1.608 1.00 25.19 C ATOM 789 O LEU A 248 ■27.233 24.605 -7.187 1.00 36.91 O

ANISOU 744 C SER A 243 3141 3224 3206 -39 -98 -240 C ANISOU 789 O LEU A 248 5242 3231 5549 -535 468 -739 O

ATOM 745 O SERA 243 ■30.565 38.827 -1.132 1.00 20.41 O ATOM 790 N GLU A 249 -28.640 22.891 -6.765 1.00 31.85 N

ANISOU 745 O SER A 243 2619 2574 2562 -43 -80 -199 O ANISOU 790 N GLU A 249 4622 2383 5097 -740 565 -795 N

ATOM 746 N VAL A 244 -32.672 38.363 -1.796 1.00 21.22 N ATOM 791 CA GLU A 249 -27.635 21.845 -6.886 1.00 38.51 C

ANISOU 746 N VAL A 244 2574 2741 2747 -107 -90 -270 N ANISOU 791 CA GLU A 249 5534 2976 6124 -683 682 -801 C

ATOM 747 CA VAL A 244 -32.644 36.958 -1.403 1.00 22.25 C ATOM 792 CB GLU A 249 -27.110 21.539 -5.496 1.00 37.38 C

ANISOU 747 CA VAL A 244 2742 2820 2890 -196 -44 -257 C ANISOU 792 CB GLU A 249 5393 2716 6094 -586 702 -551 C

ATOM 748 CB VAL A 244 -33.950 36.586 -0.721 1.00 24.58 C ATOM 793 CG GLU A 249 -25.848 20.719 -5.443 1.00 58.08 C

ANISOU 748 CB VAL A 244 2949 3157 3232 -272 17 -278 C ANISOU 793 CG GLU A 249 8057 5104 8908 -467 796 -489 C

ATOM 749 CGI VAL A 244 -33.926 35.109 -0.342 1.00 23.73 C ATOM 794 CD GLU A 249 -25.417 20.442 -4.002 1.00 68.73 C

ANISOU 749 CGI VAL A 244 2889 2979 3150 -372 70 -251 C ANISOU 794 CD GLU A 249 9399 6366 10350 -380 788 -208 C

ATOM 750 CG2 VAL A 244 -34.138 37.453 0.502 1.00 24.35 C ATOM 795 OE1 GLU A 249 -26.257 19.927 -3.221 1.00 72.66 O

ANISOU 750 CG2 VAL A 244 2901 3176 3177 -245 86 -264 C ANISOU 795 OE1 GLU A 249 9907 6808 10891 -475 804 -116 O

ATOM 751 C VAL A 244 -32.519 36.072 -2.640 1.00 19.66 C ATOM 796 OE2 GLU A 249 -24.253 20.764 -3.650 1.00 65.39 O

ANISOU 751 C VAL A 244 2435 2453 2580 -233 -92 -295 C ANISOU 796 OE2 GLU A 249 8953 5948 9943 -227 760 -75 O

ATOM 752 O VAL A 244 -33.279 36.219 -3.595 1.00 21.30 O ATOM 797 C GLU A 249 -28.379 20.644 -7.440 1.00 45.56 C

ANISOU 752 O VAL A 244 2574 2718 2801 -249 -149 -348 O ANISOU 797 C GLU A 249 6466 3706 7137 -847 775 -973 C

ATOM 753 N TYR A 245 -31.543 35.155 -2.636 1.00 19.50 N ATOM 798 O GLU A 249 -29.413 20.267 -6.891 1.00 50.73 O

ANISOU 753 N TYR A 245 2507 2339 2563 -248 -69 -268 N ANISOU 798 O GLU A 249 7100 4346 7828 -965 775 -942 O

ATOM 754 CA TYR A 245 -31.325 34.283 -3.786 1.00 21.54 C ATOM 799 N ASN A 250 -27.881 20.058 -8.539 1.00 45.94 N

ANISOU 754 CA TYR A 245 2798 2544 2841 -287 -90 -327 C ANISOU 799 N ASN A 250 6570 3640 7244 -867 861 -1167 N

ATOM 755 CB TYR A 245 -29.903 34.467 -4.296 1.00 22.35 C ATOM 800 CA ASN A 250 -28.553 18.931 -9.185 1.00 55.73 C

ANISOU 755 CB TYR A 245 2982 2599 2910 -213 -105 -308 C ANISOU 800 CA ASN A 250 7843 4768 8563 -1022 937 -1346 C

ATOM 756 CG TYR A 245 -29.661 35.834 -4.853 1.00 20.09 C ATOM 801 CB ASN A 250 -28.425 17.654 -8.343 1.00 62.11 C

ANISOU 756 CG TYR A 245 2680 2396 2557 -137 -167 -307 C ANISOU 801 CB ASN A 250 8676 5331 9592 -997 1029 -1209 C

ATOM 757 CD1 TYR A 245 -29.297 36.873 -4.021 1.00 24.02 C ATOM 802 CG ASN A 250 -27.000 17.385 -7.880 1.00 70.00 C

ANISOU 757 CD1 TYR A 245 3175 2920 3030 -72 -165 -246 C ANISOU 802 CG ASN A 250 9694 6178 10725 -795 1085 -1051 C

ATOM 758 CE1 TYR A 245 -29.087 38.121 -4.512 1.00 23.57 C ATOM 803 OD1 ASN A 250 -26.028 17.772 -8.536 1.00 71.45 O

ANISOU 758 CE1 TYR A 245 3107 2913 2933 -7 -212 -241 C ANISOU 803 OD1 ASN A 250 9880 6399 10867 -689 1097 -1112 O

ATOM 759 CZ TYR A 245 -29.243 38.363 -5.876 1.00 27.94 C ATOM 804 ND2 ASN A 250 -26.873 16.716 -6.731 1.00 73.18 N

ANISOU 759 CZ TYR A 245 3653 3508 3454 -2 -270 -276 C ANISOU 804 ND2 ASN A 250 10101 6423 11282 -745 1115 -835 N

ATOM 760 OH TYR A 245 -29.016 39.636 -6.356 1.00 30.92 O ATOM 805 C ASN A 250 ■30.042 19.183 -9.435 1.00 56.24 C

ANISOU 760 OH TYR A 245 4026 3926 3797 63 -315 -246 O ANISOU 805 C ASN A 250 7859 4998 8510 -1215 858 -1455 C

ATOM 761 CE2 TYR A 245 -29.619 37.337 -6.753 1.00 28.11 C ATOM 806 O ASN A 250 -30.866 18.295 -9.215 1.00 59.84 O

ANISOU 761 CE2 TYR A 245 3677 3531 3474 -74 -282 -340 C ANISOU 806 O ASN A 250 8307 5377 9052 -1334 892 -1471 O

ATOM 762 CD2 TYR A 245 -29.845 36.088 -6.224 1.00 22.22 C ATOM 807 N GLY A 251 -30.381 20.402 -9.844 1.00 52.77 N

ANISOU 762 CD2 TYR A 245 2940 2719 2784 -142 -227 -366 C ANISOU 807 N GLY A 251 7365 4825 7861 -1221 733 -1488 N

ATOM 763 C TYR A 245 -31.476 32.827 -3.383 1.00 23.87 C ATOM 808 CA GLY A 251 -31.746 20.723 -10.222 1.00 53.96 C ANISOU 808 CA GLY A 251 7442 5173 7887 -1384 635 -1586 C ANISOU 853 N VAL A 258 2757 2428 2500 -192 45 14 N

ATOM 809 C GLY A 251 -32.710 21.053 -9.092 1.00 66.52 C ATOM 854 CA VAL A 258 -28.966 37.158 1.272 1.00 23.24 C

ANISOU 809 C GLY A 251 8942 6847 9484 -1411 576 -1422 C ANISOU 854 CA VAL A 258 3119 2865 2848 -125 7 -42 C

ATOM 810 O GLY A 251 -33.908 21.212 -9.336 1.00 67.45 O ATOM 855 CB VAL A 258 -29.117 38.083 2.466 1.00 27.42 C

ANISOU 810 O GLY A 251 8978 7114 9535 -1550 507 -1499 O ANISOU 855 CB VAL A 258 3643 3471 3304 -134 45 -44 C

ATOM 811 N GLN A 252 -32.213 21.154 -7.857 1.00 60.21 N ATOM 856 CGI VAL A 258 -29.060 39.550 2.003 1.00 28.03 C

ANISOU 811 N GLN A 252 8151 5968 8760 -1284 604 -1198 N ANISOU 856 CGI VAL A 258 3696 3576 3380 -66 20 -111 C

ATOM 812 CA GLN A 252 -33.083 21.373 -6.694 1.0048.70 C ATOM 857 CG2 VAL A 258 -30.442 37.798 3.161 1.00 30.52 C

ANISOU 812 CA GLN A 252 6619 4575 7308 -1318 579 -1045 C ANISOU 857 CG2 VAL A 258 3985 3908 3705 -204 121 -67 C

ATOM 813 CB GLN A 252 -33.271 20.070 -5.937 1.00 55.37 C ATOM 858 C VAL A 258 -27.556 37.317 0.741 1.00 26.76 C

ANISOU 813 CB GLN A 252 7512 5168 8358 -1403 704 -981 C ANISOU 858 C VAL A 258 3615 3271 3283 -63 -44 -11 C

ATOM 814 CG GLN A 252 -33.725 18.948 -6.827 1.00 65.46 C ATOM 859 O VAL A 258 -26.611 37.090 1.464 1.00 24.60 O

ANISOU 814 CG GLN A 252 8828 6296 9749 -1578 781 -1198 C ANISOU 859 O VAL A 258 3381 2989 2977 -60 -48 64 O

ATOM 815 CD GLN A 252 -34.827 18.177 -6.198 1.00 86.42 C ATOM 860 N LEU A 259 -27.430 37.732 -0.531 1.00 20.03 N ANISOU 815 CD GLN A 252 11447 8873 12515 -1748 838 -1173 C ANISOU 860 N LEU A 259 2751 2406 2454 -18 -85 -64 N

ATOM 816 OE1 GLN A 252 -35.840 17.856 -6.832 1.00 90.96 O ATOM 861 CA LEU A 259 -26.132 37.752 -1.180 1.00 22.36 C ANISOU 816 OE1 GLN A 252 11964 9539 13057 -1899 807 -1323 O ANISOU 861 CA LEU A 259 3087 2662 2749 31 -116 -44 C

ATOM 817 NE2 GLN A 252 -34.652 17.874 -4.924 1.00 96.23 N ATOM 862 CB LEU A 259 -26.194 36.757 -2.345 1.00 24.21 C ANISOU 817 NE2 GLN A 252 12714 9993 13857 -1699 900 -948 N ANISOU 862 CB LEU A 259 3330 2835 3035 18 -115 -83 C

ATOM 818 C GLN A 252 -32.500 22.411 -5.746 1.00 45.33 C ATOM 863 CG LEU A 259 -25.254 35.608 -2.526 1.00 40.60 C

ANISOU 818 C GLN A 252 6171 4254 6797 -1147 523 -836 C ANISOU 863 CG LEU A 259 5445 4816 5164 25 -91 -51 C

ATOM 819 0 GLN A 252 -31.282 22.524 -5.634 1.00 37.69 O ATOM 864 CD1 LEU A 259 -24.920 34.948 -1.220 1.00 37.34 C

ANISOU 819 O GLN A 252 5262 3213 5845 -1004 540 -758 O ANISOU 864 CD1 LEU A 259 5046 4369 4772 12 -67 50 C

ATOM 820 N ARG A 253 -33.369 23.148 -5.052 1.0040.98 N ATOM 865 CD2 LEU A 259 -25.982 34.616 -3.438 1.00 34.53 C

ANISOU 820 N ARG A 253 5532 3874 6165 -1167 465 -755 N ANISOU 865 CD2 LEU A 259 4678 3995 4447 -28 -69 -129 C

ATOM 821 CA ARG A 253 -32.894 24.207 -4.172 1.00 41.24 C ATOM 866 C LEU A 259 -25.929 39.103 -1.798 1.00 21.18 C

ANISOU 821 CA ARG A 253 5545 4021 6103 -1024 415 -588 C ANISOU 866 C LEU A 259 2926 2550 2569 80 -150 -78 C

ATOM 822 CB ARG A 253 -34.024 25.098 -3.664 1.00 35.88 C ATOM 867 O LEU A 259 -26.867 39.673 -2.367 1.00 22.04 O

ANISOU 822 CB ARG A 253 4753 3546 5333 -1061 359 -560 C ANISOU 867 O LEU A 259 2996 2692 2685 87 -166 -125 O

ATOM 823 CG ARG A 253 -33.483 26.346 -2.958 1.00 31.49 C ATOM 868 N GLU A 260 -24.704 39.621 -1.780 1.00 23.51 N

ANISOU 823 CG ARG A 253 4184 3117 4664 -915 307 -434 C ANISOU 868 N GLU A 260 3250 2840 2843 116 -166 -48 N

ATOM 824 CD ARG A 253 -34.571 27.205 -2.347 1.00 36.84 C ATOM 869 CA GLU A 260 -24.434 40.773 -2.643 1.00 25.73 C

ANISOU 824 CD ARG A 253 4751 3971 5276 -941 281 -411 C ANISOU 869 CA GLU A 260 3531 3136 3111 157 -192 -73 C

ATOM 825 NE ARG A 253 -35.447 26.375 -1.544 1.0045.19 N ATOM 870 CB GLU A 260 -25.032 42.055 -2.061 1.00 25.76 C

ANISOU 825 NE ARG A 253 5781 4974 6414 -1069 366 -370 N ANISOU 870 CB GLU A 260 3512 3172 3103 166 -188 -95 C

ATOM 826 CZ ARG A 253 -36.683 26.059 -1.912 1.00 54.51 C ATOM 871 CG GLU A 260 -24.481 42.402 -0.730 1.00 26.16 C

ANISOU 826 CZ ARG A 253 6868 6204 7639 -1206 372 -472 C ANISOU 871 CG GLU A 260 3579 3242 3118 143 -167 -80 C

ATOM 827 NHl ARG A 253 -37.180 26.538 -3.051 1.00 50.43 N ATOM 872 CD GLU A 260 -25.329 43.511 -0.074 1.0046.27 C ANISOU 827 NHl ARG A 253 6273 5805 7082 -1223 281 -609 N ANISOU 872 CD GLU A 260 6104 5811 5666 141 -133 -133 C

ATOM 828 NH2 ARG A 253 -37.418 25.271 -1.145 1.00 56.92 N ATOM 873 OE1 GLU A 260 -26.576 43.404 -0.112 1.00 39.73 O ANISOU 828 ΝΉ2 ARG A 253 7151 6449 8025 -1331 463 -427 N ANISOU 873 OE1 GLU A 260 5232 4994 4870 142 -112 -163 O

ATOM 829 C ARG A 253 -32.129 23.587 -3.000 1.00 34.42 C ATOM 874 OE2 GLU A 260 -24.754 44.479 0.449 1.00 42.71 O

ANISOU 829 C ARG A 253 4750 2991 5335 -961 491 -398 C ANISOU 874 OE2 GLU A 260 5673 5361 5193 137 -123 -153 O

ATOM 830 O ARG A 253 -32.591 22.638 -2.368 1.00 39.52 O ATOM 875 C GLU A 260 -22.951 40.986 -2.888 1.00 26.03 C

ANISOU 830 O ARG A 253 5414 3507 6094 -1055 570 -338 O ANISOU 875 C GLU A 260 3594 3155 3140 182 -200 -42 C

ATOM 831 N ALA A 254 -30.947 24.103 -2.740 1.00 34.10 N ATOM 876 0 GLU A 260 -22.122 40.583 -2.102 1.00 22.38 O

ANISOU 831 N ALA A 254 4746 2955 5254 -809 462 -297 N ANISOU 876 O GLU A 260 3137 2688 2679 175 -197 4 O

ATOM 832 CA ALA A 254 -30.088 23.540 -1.708 1.0041.66 C ATOM 877 N TYR A 261 -22.624 41.632 -3.993 1.00 25.36 N

ANISOU 832 CA ALA A 254 5762 3772 6295 -736 511 -104 C ANISOU 877 N TYR A 261 3519 3071 3047 208 -214 -56 N

ATOM 833 CB ALA A 254 -28.793 22.995 -2.323 1.00 33.59 C ATOM 878 CA TYR A 261 -21.214 41.968 -4.227 1.00 22.95 C

ANISOU 833 CB ALA A 254 4800 2581 5380 -635 544 -120 C ANISOU 878 CA TYR A 261 3226 2755 2739 224 -210 -29 C

ATOM 834 C ALA A 254 -29.789 24.581 -0.629 1.00 32.23 C ATOM 879 CB TYR A 261 -20.993 42.352 -5.678 1.00 20.10 C

ANISOU 834 C ALA A 254 4541 2737 4966 -651 449 55 C ANISOU 879 CB TYR A 261 2883 2396 2359 239 -210 -44 C

ATOM 835 O ALA A 254 -29.318 24.257 0.449 1.00 31.77 O ATOM 880 CG TYR A 261 -21.076 41.195 -6.634 1.00 23.37 C

ANISOU 835 O ALA A 254 4516 2624 4932 -616 468 239 O ANISOU 880 CG TYR A 261 3309 2797 2773 231 -190 -79 C

ATOM 836 N GLY A 255 -30.110 25.831 -0.915 1.00 26.46 N ATOM 881 CD1 TYR A 261 -20.113 40.202 -6.623 1.00 24.12 C

ANISOU 836 N GLY A 255 3753 2208 4093 -627 374 -18 N ANISOU 881 CD1 TYR A 261 3404 2851 2910 239 -149 -79 C

ATOM 837 CA GLY A 255 -29.898 26.891 0.056 1.00 29.48 C ATOM 882 CE1 TYR A 261 -20.179 39.131 -7.508 1.00 21.52 C

ANISOU 837 CA GLY A 255 4112 2741 4347 -561 327 94 C ANISOU 882 CE1 TYR A 261 3092 2491 2592 226 -112 -134 C

ATOM 838 C GLY A 255 -30.615 28.138 -0.375 1.00 26.32 C ATOM 883 CZ TYR A 261 -21.227 39.070 -8.413 1.00 25.94 C

ANISOU 838 C GLY A 255 3639 2530 3833 -562 267 -15 C ANISOU 883 CZ TYR A 261 3672 3086 3098 191 -130 -191 C

ATOM 839 O GLY A 255 -31.012 28.283 -1.535 1.00 25.81 O ATOM 884 0H TYR A 261 -21.305 38.024 -9.287 1.00 28.34 O

ANISOU 839 O GLY A 255 3543 2493 3770 -585 237 -158 O ANISOU 884 OH TYR A 261 4001 3366 3401 159 -90 -269 O

ATOM 840 N THR A 256 -30.772 29.064 0.573 1.00 23.65 N ATOM 885 CE2 TYR A 261 -22.197 40.039 -8.445 1.00 27.78 C

ANISOU 840 N THR A 256 3271 2322 3391 -536 249 56 N ANISOU 885 CE2 TYR A 261 3895 3378 3283 186 -190 -174 C

ATOM 841 CA THR A 256 -31.410 30.344 0.301 1.00 22.76 C ATOM 886 CD2 TYR A 261 -22.117 41.111 -7.559 1.00 30.51 C

ANISOU 841 CA THR A 256 3084 2372 3191 -516 202 -29 C ANISOU 886 CD2 TYR A 261 4221 3731 3640 214 -212 -117 C

ATOM 842 CB THR A 256 -32.889 30.336 0.741 1.00 30.71 C ATOM 887 C TYR A 261 -20.804 43.135 -3.346 1.00 24.77 C

ANISOU 842 CB THR A 256 4009 3455 4206 -619 246 -64 C ANISOU 887 C TYR A 261 3452 3003 2955 217 -218 -17 C

ATOM 843 OG1 THR A 256 -33.585 29.233 0.152 1.00 33.73 O ATOM 888 O TYR A 261 -21.569 44.050 -3.102 1.00 22.54 O

ANISOU 843 OG1 THR A 256 4375 3752 4690 -727 279 -129 O ANISOU 888 O TYR A 261 3169 2726 2668 217 -219 -41 O

ATOM 844 CG2 THR A 256 -33.586 31.647 0.363 1.00 28.54 C ATOM 889 N ALA A 262 -19.558 43.108 -2.881 1.00 24.80 N

ANISOU 844 CG2 THR A 256 3638 3332 3876 -581 197 -150 C ANISOU 889 N ALA A 262 3448 3015 2962 209 -221 16 N

ATOM 845 C THR A 256 -30.667 31.360 1.150 1.00 28.61 C ATOM 890 CA ALA A 262 -18.990 44.245 -2.199 1.00 21.10 C

ANISOU 845 C THR A 256 3844 3197 3831 -432 176 52 C ANISOU 890 CA ALA A 262 2976 2566 2474 183 -230 13 C

ATOM 846 O THR A 256 -30.492 31.139 2.357 1.00 27.63 O ATOM 891 CB ALA A 262 -17.694 43.849 -1.540 1.00 22.62 C

ANISOU 846 O THR A 256 3750 3077 3671 -454 213 166 O ANISOU 891 CB ALA A 262 3137 2790 2667 165 -250 59 C

ATOM 847 N CYS A 257 -30.229 32.465 0.554 1.00 23.84 N ATOM 892 C ALA A 262 -18.756 45.394 -3.183 1.00 26.11 C

ANISOU 847 N CYS A 257 3225 2661 3172 -349 114 -1 N ANISOU 892 C ALA A 262 3626 3173 3121 194 -219 -1 C

ATOM 848 CA CYS A 257 -29.446 33.420 1.335 1.00 21.24 C ATOM 893 O ALA A 262 -17.934 45.313 -4.114 1.00 23.10 O

ANISOU 848 CA CYS A 257 2918 2400 2754 -283 92 62 C ANISOU 893 O ALA A 262 3242 2784 2751 206 -208 19 O

ATOM 849 CB CYS A 257 -28.009 32.962 1.443 1.00 29.26 C ATOM 894 N THR A 263 -19.430 46.515 -2.945 1.00 22.72 N

ANISOU 849 CB CYS A 257 3998 3337 3781 -228 70 152 C ANISOU 894 N THR A 263 3212 2724 2695 189 -212 -33 N

ATOM 850 SG CYS A 257 -27.290 32.878 -0.152 1.00 47.49 S ATOM 895 CA THR A 263 -19.363 47.633 -3.882 1.00 20.75 C

ANISOU 850 SG CYS A 257 6318 5576 6148 -165 33 70 S ANISOU 895 CA THR A 263 2983 2429 2470 205 -201 -24 C

ATOM 851 C CYS A 257 -29.497 34.828 0.785 1.00 26.04 C ATOM 896 CB THR A 263 -20.320 48.754 -3.439 1.00 20.95 C

ANISOU 851 C CYS A 257 3486 3096 3313 -220 44 -16 C ANISOU 896 CB THR A 263 3018 2410 2531 215 -186 -60 C

ATOM 852 O CYS A 257 -29.819 35.058 -0.393 1.00 21.50 O ATOM 897 OG1 THR A 263 -20.009 49.119 -2.086 1.00 24.23 O

ANISOU 852 O CYS A 257 2880 2525 2765 -203 6 -96 O ANISOU 897 OG1 THR A 263 3433 2836 2937 162 -168 -113 O

ATOM 853 N VAL A 258 -29.160 35.764 1.659 1.00 20.23 N ATOM 898 CG2 THR A 263 -21.780 48.259 -3.504 1.00 23.24 C

 ANISOU 988 CD2 TYR A 274 5873 4662 4979 -130 210 727 C ANISOU 1033 C ARG A 281 3522 4747 3395 146 947 -663 C ATOM 989 C TYR A 274 -7.954 56.008 -15.653 1.00 35.57 C ATOM 1034 O ARG A 281 -4.145 44.638 -11.502 1.00 26.26 O ANISOU 989 C TYR A 274 5067 4188 4261 -441 571 713 C ANISOU 1034 O ARG A 281 3035 4053 2889 137 750 -706 O ATOM 990 O TYR A 274 -7.429 55.832 -14.553 1.00 37.85 O ATOM 1035 CA AARG A 281 -4.011 46.014 -13.484 0.51 31.58 C ANISOU 990 O TYR A 274 5263 4464 4656 -451 551 617 O ANISOU 1035 CA AARG A 281 3682 5189 3127 39 1013 -490 C ATOM 991 N SERA 275 -7.295 56.493 -16.697 1.00 33.77 N ATOM 1036 CB AARG A 281 -4.120 45.147 -14.737 0.51 36.30 C ANISOU 991 N SER A 275 4871 3983 3976 -523 674 802 N ANISOU 1036 CB AARG A 281 4441 6023 3330 -84 1150 -739 C ATOM 992 CA SER A 275 -5.847 56.662 -16.642 1.00 40.71 C ATOM 1037 CG AARG A 281 -4.698 45.912 -15.913 0.51 36.81 C ANISOU 992 CA SER A 275 5656 4886 4926 -625 785 770 C ANISOU 1037 CG AARG A 281 4510 6566 2909 -165 1180 -504 C ATOM 993 CB SER A 275 -5.257 56.889 -18.035 1.0046.55 C ATOM 1038 CD AARG A 281 -5.305 45.005 -16.984 0.51 46.03 C ANISOU 993 CB SER A 275 6440 5693 5554 -707 917 865 C ANISOU 1038 CD AARG A 281 5822 8136 3531 -406 1185 -799 C ATOM 994 OG SER A 275 -5.041 58.260 -18.291 1.00 47.46 O ATOM 1039 NE AARG A 281 -4.404 43.964 -17.487 0.51 40.95 N ANISOU 994 OG SER A 275 6616 5697 5718 -802 962 992 O ANISOU 1039 NE AARG A 281 5323 7329 2908 -485 1495 -1250 N ATOM 995 C SER A 275 -5.406 57.759 -15.635 1.0049.10 C ATOM 1040 CZ AARG A 281 -3.483 44.147 -18.426 0.51 43.75 C ANISOU 995 C SER A 275 6682 5819 6157 -699 772 762 C ANISOU 1040 CZ AARG A 281 5711 7738 3173 -446 1780 -1260 C ATOM 996 O SERA 275 -4.282 57.737 -15.114 1.00 44.36 O ATOM 1041 NH1AARG A 281 -3.299 45.347 -18.964 0.51 46.70 N ANISOU 996 O SER A 275 5962 5245 5646 -773 818 693 O ANISOU 1041 NH1AARG A 281 5996 8353 3396 -335 1834 -859 N ATOM 997 N GLN A 276 -6.287 58.707 -15.330 1.00 42.88 N ATOM 1042 NH2AARG A 281 -2.731 43.129 -18.821 0.51 49.21 N ANISOU 997 N GLN A 276 5985 4890 5418 -682 710 822 N ANISOU 1042 NH2AARG A 281 6532 8162 4002 -486 2042 -1618 N ATOM 998 CA GLN A 276 -5.909 59.695 -14.327 1.00 51.79 C ATOM 1043 CA BARG A 281 -4.019 46.022 -13.485 0.49 31.54 C ANISOU 998 CA GLN A 276 7085 5888 6706 -759 706 780 C ANISOU 1043 CA BARG A 281 3677 5186 3121 39 1012 -487 C ATOM 999 CB GLN A 276 -6.823 60.933 -14.358 1.00 49.84 C ATOM 1044 CB BARG A 281 -4.154 45.161 -14.745 0.49 35.97 C ANISOU 999 CB GLN A 276 6960 5452 6525 -748 684 877 C ANISOU 1044 CB BARG A 281 4399 5989 3278 -87 1145 -733 C ATOM 1000 CG GLN A 276 -8.258 60.701 -13.884 1.00 48.87 C ATOM 1045 CG BARG A 281 -4.775 45.900 -15.939 0.49 36.87 C ANISOU 1000 CG GLN A 276 6887 5288 6394 -610 571 857 C ANISOU 1045 CG BARG A 281 4522 6596 2891 -174 1168 -502 C ATOM 1001 CD GLN A 276 -9.008 62.021 -13.631 1.00 68.61 C ATOM 1046 CD BARG A 281 -6.094 46.605 -15.575 0.49 33.65 C ANISOU 1001 CD GLN A 276 9474 7573 9023 -599 563 923 C ANISOU 1046 CD BARG A 281 4034 6380 2370 -179 894 -150 C ATOM 1002 OE1 GLN A 276 -10.096 62.244 -14.167 1.00 73.21 O ATOM 1047 NE BARG A 281 -6.653 47.387 -16.688 0.49 42.90 N ANISOU 1002 OE1 GLN A 276 10132 8103 9580 -502 518 1036 O ANISOU 1047 NE BARG A 281 5143 8091 3067 -170 928 215 N ATOM 1003 NE2 GLN A 276 -8.419 62.898 -12.814 1.00 65.72 N ATOM 1048 CZ BARG A 281 -7.751 47.057 -17.369 0.49 49.92 C ANISOU 1003 NE2 GLN A 276 9090 7078 8804 -700 608 849 N ANISOU 1048 CZ BARG A 281 6014 9414 3537 -311 696 223 C ATOM 1004 C GLN A 276 -5.809 59.086 -12.907 1.00 48.36 C ATOM 1049 NH1BARG A 281 -8.432 45.959 -17.045 0.49 50.52 N ANISOU 1004 C GLN A 276 6549 5491 6335 -733 624 621 C ANISOU 1049 NH1BARG A 281 6146 9496 3555 -530 494 -161 N ATOM 1005 O GLN A 276 -5.309 59.743 -11.983 1.00 46.50 O ATOM 1050 NH2BARG A 281 -8.179 47.834 -18.366 0.49 45.31 N ANISOU 1005 O GLN A 276 6268 5189 6212 -820 619 552 O ANISOU 1050 NH2BARG A 281 5329 9166 2719 -225 670 602 N ATOM 1006 N ALA A 277 -6.286 57.844 -12.729 1.00 36.82 N ATOM 1051 N GLU A 282 -2.095 45.214 -12.221 1.00 28.82 N ANISOU 1006 N ALA A 277 5056 4137 4796 -625 559 564 N ANISOU 1051 N GLU A 282 3128 4411 3411 269 1126 -724 N ATOM 1007 CA ALA A 277 -6.128 57.149 -11.442 1.00 38.50 C ATOM 1052 CA GLU A 282 -1.444 44.528 -11.103 1.00 32.36 C ANISOU 1007 CA ALA A 277 5171 4405 5052 -602 482 440 C ANISOU 1052 CA GLU A 282 3444 4666 4187 436 1054 -782 C ATOM 1008 CB ALA A 277 -7.175 56.061 -11.272 1.00 34.08 C ATOM 1053 CB GLU A 282 0.068 44.386 -11.297 1.00 31.88 C ANISOU 1008 CB ALA A 277 4635 3899 4416 -470 402 410 C ANISOU 1053 CB GLU A 282 3150 4595 4367 589 1293 -841 C ATOM 1009 C ALA A 277 -4.707 56.580 -11.194 1.00 52.09 C ATOM 1054 CG GLU A 282 0.415 43.269 -12.244 1.00 43.11 C ANISOU 1009 C ALA A 277 6739 6240 6813 -664 519 386 C ANISOU 1054 CG GLU A 282 4725 5902 5752 659 1605 -1039 C ATOM 1010 O ALA A 277 -4.350 56.286 -10.050 1.00 46.35 O ATOM 1055 CD GLU A 282 1.914 43.029 -12.359 1.00 63.96 C ANISOU 1010 O ALA A 277 5918 5555 6136 -679 451 304 O ANISOU 1055 CD GLU A 282 7099 8500 8705 864 1878 -1060 C ATOM 1011 N GLY A 278 -3.916 56.410 -12.259 1.00 47.00 N ATOM 1056 OE1 GLU A 282 2.303 42.117 -13.130 1.00 60.73 O ANISOU 1011 N GLY A 278 6061 5656 6141 -700 625 435 N ANISOU 1056 OE1 GLU A 282 6811 7934 8329 935 2231 -1231 O ATOM 1012 CA GLY A 278 -2.535 55.944 -12.142 1.00 50.39 C ATOM 1057 OE2 GLU A 282 2.690 43.748 -11.679 1.00 73.40 O ANISOU 1012 CA GLY A 278 6326 6190 6632 -755 679 394 C ANISOU 1057 OE2 GLU A 282 7944 9831 10115 927 1770 -933 O ATOM 1013 C GLY A 278 -2.407 54.518 -11.617 1.00 52.27 C ATOM 1058 C GLU A 282 -1.743 45.236 -9.813 1.00 30.21 C ANISOU 1013 C GLY A 278 6457 6533 6871 -653 622 328 C ANISOU 1058 C GLU A 282 3041 4388 4050 415 793 -630 C ATOM 1014 O GLY A 278 -1.446 54.156 -10.924 1.00 50.66 O ATOM 1059 O GLU A 282 -2.002 44.580 -8.807 1.00 31.89 O ANISOU 1014 O GLY A 278 6095 6402 6751 -679 602 285 O ANISOU 1059 O GLU A 282 3267 4497 4353 504 617 -620 O ATOM 1015 N PHE A 279 -3.372 53.685 -11.987 1.00 39.00 N ATOM 1060 N ASP A 283 -1.746 46.574 -9.838 1.00 27.88 N ANISOU 1015 N PHE A 279 4856 4860 5101 -537 597 328 N ANISOU 1060 N ASP A 283 2644 4180 3770 285 829 -513 N ATOM 1016 CA PHE A 279 -3.610 52.432 -11.303 1.00 35.20 C ATOM 1061 CA ASP A 283 -2.155 47.358 -8.667 1.00 30.45 C ANISOU 1016 CA PHE A 279 4313 4432 4627 -433 522 273 C ANISOU 1061 CA ASP A 283 2889 4471 4209 184 667 -429 C ATOM 1017 CB PHE A 279 -5.042 52.516 -10.832 1.00 40.20 C ATOM 1062 CB ASP A 283 -2.114 48.863 -8.932 1.00 33.61 C ANISOU 1017 CB PHE A 279 5070 5000 5203 -374 422 270 C ANISOU 1062 CB ASP A 283 3211 4871 4688 27 892 -322 C ATOM 1018 CG PHE A 279 -5.363 51.673 -9.664 1.00 29.70 C ATOM 1063 CG ASP A 283 -0.710 49.382 -9.198 1.00 49.77 C ANISOU 1018 CG PHE A 279 3689 3699 3895 -308 318 222 C ANISOU 1063 CG ASP A 283 5000 6983 6929 -11 1147 -435 C ATOM 1019 CD1 PHE A 279 -4.670 51.815 -8.468 1.00 34.05 C ATOM 1064 OD1 ASP A 283 0.251 48.701 -8.774 1.00 52.74 O ANISOU 1019 CD1 PHE A 279 4134 4285 4517 -358 252 193 C ANISOU 1064 OD1 ASP A 283 5167 7462 7409 75 1057 -587 O ATOM 1020 CE1 PHE A 279 -5.017 51.071 -7.353 1.00 30.63 C ATOM 1065 OD2 ASP A 283 -0.586 50.463 -9.847 1.00 53.92 O ANISOU 1020 CE1 PHE A 279 3666 3888 4083 -305 150 168 C ANISOU 1065 OD2 ASP A 283 5511 7456 7518 -105 1472 -337 O ATOM 1021 CZ PHE A 279 -6.079 50.179 -7.423 1.00 29.15 C ATOM 1066 C ASP A 283 -3.578 47.030 -8.259 1.00 30.85 C ANISOU 1021 CZ PHE A 279 3549 3684 3841 -202 122 166 C ANISOU 1066 C ASP A 283 3162 4433 4124 152 458 -349 C ATOM 1022 CE2 PHE A 279 -6.803 50.043 -8.627 1.00 28.00 C ATOM 1067 O ASP A 283 -3.904 46.950 -7.073 1.00 25.86 O ANISOU 1022 CE2 PHE A 279 3504 3498 3635 -155 186 180 C ANISOU 1067 O ASP A 283 2520 3732 3573 138 278 -343 O ATOM 1023 CD2 PHE A 279 -6.437 50.802 -9.732 1.00 28.03 C ATOM 1068 N ARG A 284 -4.446 46.890 -9.254 1.00 23.24 N ANISOU 1023 CD2 PHE A 279 3545 3483 3623 -209 278 210 C ANISOU 1068 N ARG A 284 2374 3530 2925 119 489 -286 N ATOM 1024 C PHE A 279 -3.492 51.317 -12.329 1.00 34.75 C ATOM 1069 CA ARG A 284 -5.849 46.617 -8.950 1.00 22.39 C ANISOU 1024 C PHE A 279 4246 4436 4523 -361 610 263 C ANISOU 1069 CA ARG A 284 2419 3392 2696 59 301 -217 C ATOM 1025 O PHE A 279 -4.336 51.199 -13.208 1.00 45.87 O ATOM 1070 CB ARG A 284 -6.679 46.520 -10.237 1.00 22.88 C ANISOU 1025 O PHE A 279 5777 5828 5822 -328 636 281 O ANISOU 1070 CB ARG A 284 2575 3700 2419 -12 325 -159 C ATOM 1026 N SER A 280 -2.463 50.478 -12.222 1.00 31.76 N ATOM 1071 CG ARG A 284 -8.154 46.846 -9.962 1.00 29.86 C ANISOU 1026 N SER A 280 3715 4126 4227 -336 657 230 N ANISOU 1071 CG ARG A 284 3484 4646 3217 -83 161 37 C ATOM 1027 CA SER A 280 -2.288 49.395 -13.195 1.00 26.67 C ATOM 1072 CD ARG A 284 -9.144 45.712 -10.189 1.00 37.19 C ANISOU 1027 CA SERA 280 3056 3523 3555 -269 766 195 C ANISOU 1072 CD ARG A 284 4521 5680 3928 -202 5 -153 C ATOM 1028 CB SER A 280 -0.843 48.922 -13.202 1.00 36.47 C ATOM 1073 NE ARG A 284 -8.592 44.431 -10.656 1.00 37.63 N ANISOU 1028 CB SER A 280 4102 4828 4926 -271 857 173 C ANISOU 1073 NE ARG A 284 4699 5698 3901 -251 98 -525 N ATOM 1029 OG SERA 280 -0.555 48.249 -12.000 1.00 32.54 O ATOM 1074 CZ ARG A 284 -8.880 43.253 -10.082 1.00 37.19 C ANISOU 1029 OG SER A 280 3475 4344 4544 -205 751 166 O ANISOU 1074 CZ ARG A 284 4778 5392 3962 -294 89 -776 C ATOM 1030 C SER A 280 -3.174 48.196 -12.871 1.00 29.69 C ATOM 1075 NHl ARG A 284 -8.368 42.117 -10.558 1.00 30.72 N ANISOU 1030 C SER A 280 3476 3887 3919 -151 699 154 C ANISOU 1075 NHl ARG A 284 4082 4463 3129 -331 300 -1106 N ATOM 1031 O SER A 280 -3.796 48.128 -11.830 1.00 28.25 O ATOM 1076 ΝΉ2 ARG A 284 -9.721 43.214 -9.045 1.00 33.12 N ANISOU 1031 O SER A 280 3308 3674 3751 -118 570 161 O ANISOU 1076 ΝΉ2 ARG A 284 4287 4697 3599 -301 -61 -690 N ATOM 1032 N ARG A 281 -3.222 47.210 -13.768 1.00 31.32 N ATOM 1077 C ARG A 284 -5.992 45.310 -8.182 1.00 23.57 C ANISOU 1032 N ARG A 281 3507 5175 3217 104 1232 -276 N ANISOU 1077 C ARG A 284 2669 3376 2910 123 163 -384 C ATOM 1033 C ARG A 281 -3.418 45.225 -12.314 1.00 30.70 C ATOM 1078 O ARG A 284 -6.709 45.226 -7.178 1.00 24.32 O ANISOU 1078 O ARG A 284 2818 3344 3076 105 11 -332 O ANISOU 1123 CD1 LEU A 290 3788 6488 4769 380 -1072 -40 ATOM 1079 N LEU A 285 -5.326 44.270 -8.669 1.00 23.14 N ATOM 1124 CD2 LEU A 290 -3.151 46.875 1.008 1.00 36.66 ANISOU 1079 N LEU A 285 2658 3282 2854 212 287 -567 N ANISOU 1124 CD2 LEU A 290 3267 5982 4680 -88 -762 -448 ATOM 1080 CA LEU A 285 -5.409 42.961 -8.013 1.00 22.03 C ATOM 1125 c LEU A 290 -6.956 44.341 1.066 1.00 26.87 C ANISOU 1080 CA LEU A 285 2628 2907 2834 325 287 -676 C ANISOU 1125 c LEU A 290 3128 3568 3515 352 -726 5 C ATOM 1081 CB LEU A 285 -4.683 41.899 -8.840 1.00 25.04 c ATOM 1126 0 LEU A 290 -7.141 44.412 2.282 1.00 24.10 o ANISOU 1081 CB LEU A 285 3074 3193 3248 409 576 -884 c ANISOU 1126 0 LEU A 290 2798 3327 3031 317 -821 59 o ATOM 1082 CG LEU A 285 -4.777 40.518 -8.185 1.00 32.57 c ATOM 1127 N PHE A 291 -7.888 44.698 0.173 1.00 19.53 N ANISOU 1082 CG LEU A 285 4162 3807 4406 565 710 -950 c ANISOU 1127 N PHE A 291 2355 2384 2682 202 -617 -58 N ATOM 1083 CD1 LEU A 285 -6.212 40.009 -8.165 1.00 39.55 c ATOM 1128 CA PHE A 291 -9.209 45.154 0.617 1.00 22.58 C ANISOU 1083 CD1 LEU A 285 5279 4575 5172 344 674 -1095 ANISOU 1128 CA PHE A 291 2927 2560 3093 23 -587 -39 c ATOM 1084 CD2 LEU A 285 -3.883 39.577 -8.965 1.00 40.85 ATOM 1129 CB PHE A 291 -10.063 45.543 -0.594 1.00 25.93 c ANISOU 1084 CD2 LEU A 285 5250 4691 5580 682 1111 -1131 ANISOU 1129 CB PHE A 291 3402 2853 3598 -82 -488 -36 c ATOM 1085 C LEU A 285 -4.821 42.996 -6.590 1.00 26.28 c ATOM 1130 CG PHE A 291 -11.531 45.717 -0.273 1.00 22.05 c ANISOU 1085 C LEU A 285 3020 3376 3591 506 162 -532 c ANISOU 1130 CG PHE A 291 3057 2150 3172 -194 -452 38 c ATOM 1086 O LEU A 285 -5.395 42.442 -5.638 1.00 27.21 o ATOM 1131 CD1 PHE A 291 -11.981 46.887 0.308 1.00 19.19 c ANISOU 1086 O LEU A 285 3236 3339 3763 567 64 -473 o ANISOU 1131 CD1 PHE A 291 2672 1741 2877 -347 -328 83 c ATOM 1087 N GLU A 286 -3.673 43.641 -6.453 1.00 24.82 N ATOM 1132 CE1 PHE A 291 -13.339 47.065 0.575 1.00 21.29 c ANISOU 1087 N GLU A 286 2576 3357 3497 572 175 -481 N ANISOU 1132 CE1 PHE A 291 2963 2017 3108 -318 -143 124 c ATOM 1088 CA GLU A 286 -2.997 43.764 -5.155 1.00 28.42 c ATOM 1133 CZ PHE A 291 -14.250 46.054 0.269 1.00 17.04 c ANISOU 1088 CA GLU A 286 2802 3931 4064 692 22 -372 c ANISOU 1133 CZ PHE A 291 2460 1471 2542 -256 -182 131 c ATOM 1089 CB GLU A 286 -1.705 44.555 -5.327 1.00 36.43 c ATOM 1134 CE2 PHE A 291 -13.818 44.896 -0.332 1.00 27.49 c ANISOU 1089 CB GLU A 286 3477 5203 5161 667 82 -408 c ANISOU 1134 CE2 PHE A 291 3847 2742 3854 -216 -331 77 c ATOM 1090 CG GLU A 286 -0.926 44.728 -4.045 1.00 51.92 c ATOM 1135 CD2 PHE A 291 -12.454 44.723 -0.601 1.00 29.77 c ANISOU 1090 CG GLU A 286 5108 7458 7160 725 -105 -345 c ANISOU 1135 CD2 PHE A 291 4165 2988 4160 -161 -468 30 c ATOM 1091 CD GLU A 286 0.250 45.681 -4.199 1.00 77.63 c ATOM 1136 c PHE A 291 -9.873 44.041 1.394 1.00 24.77 c ANISOU 1091 CD GLU A 286 7986 11011 10499 580 -34 -464 c ANISOU 1136 c PHE A 291 3410 2648 3354 166 -615 56 c ATOM 1092 OE1 GLU A 286 0.885 45.690 -5.280 1.00 76.40 o ATOM 1137 0 PHE A 291 ■10.386 44.235 2.485 1.00 21.94 o ANISOU 1092 OE1 GLU A 286 7770 10810 10447 625 197 521 O ANISOU 1137 0 PHE A 291 3148 2246 2941 93 -634 100 o ATOM 1093 OE2 GLU A 286 0.517 46.438 -3.236 1.00 97.02 O ATOM 1138 N CYS A 292 -9.809 42.838 0.831 1.00 21.83 N ANISOU 1093 OE2 GLU A 286 10206 13749 12908 377 -173 -541 O ANISOU 1138 N CYS A 292 3119 2135 3042 364 -551 72 N ATOM 1094 C GLU A 286 -3.905 44.473 -4.149 1.00 26.26 C ATOM 1139 c CYS A 292 -9.750 41.340 2.826 1.00 29.97 c ANISOU 1094 C GLU A 286 2593 3664 3720 517 -175 -313 C ANISOU 1139 c CYS A 292 4326 3056 4003 750 -532 387 c ATOM 1095 O GLU A 286 -4.055 44.041 -2.995 1.00 24.26 o ATOM 1140 0 CYS A 292 ■10.453 41.060 3.812 1.00 28.68 o ANISOU 1095 O GLU A 286 2340 3419 3457 614 -320 -222 o ANISOU 1140 0 CYS A 292 4328 2769 3802 760 -492 497 o ATOM 1096 N GLN A 287 -4.550 45.553 -4.587 1.00 21.56 N ATOM 1141 CA ACYS A 292 -10.384 41.666 1.455 0.58 25.04 c ANISOU 1096 N GLN A 287 2060 3053 3076 283 -134 -329 N ANISOU 1141 CA ACYS A 292 3737 2274 3503 520 -462 165 c ATOM 1097 CA GLN A 287 -5.466 46.292 -3.715 1.00 23.64 C ATOM 1142 CB ACYS A 292 -10.210 40.480 0.515 0.58 29.34 c ANISOU 1097 CA GLN A 287 2399 3253 3330 111 -221 -276 c ANISOU 1142 CB ACYS A 292 4356 2611 4179 663 -265 87 c ATOM 1098 CB GLN A 287 -5.783 47.691 -4.278 1.00 23.23 c ATOM 1143 SG ACYS A 292 -10.855 38.997 1.190 0.58 32.61 s ANISOU 1098 CB GLN A 287 2323 3179 3324 -89 -40 -234 c ANISOU 1143 SG ACYS A 292 4866 2767 4755 723 -15 161 s ATOM 1099 CG GLN A 287 -4.589 48.636 -4.307 1.00 24.62 c ATOM 1144 CA BCYS A 292 -10.370 41.649 1.473 0.42 25.91 c ANISOU 1099 CG GLN A 287 2250 3489 3616 -205 129 -338 c ANISOU 1144 CA BCYS A 292 3848 2385 3613 526 -462 168 c ATOM 1100 CD GLN A 287 -3.913 48.810 -2.942 1.00 31.58 c ATOM 1145 CB BCYS A 292 -10.196 40.424 0.579 0.42 28.23 c ANISOU 1100 CD GLN A 287 2933 4546 4519 -323 15 -494 c ANISOU 1145 CB BCYS A 292 4222 2462 4042 679 -260 99 c ATOM 1101 OE1 GLN A 287 -4.548 49.235 -1.975 1.00 26.76 o ATOM 1146 SG BCYS A 292 -11.302 40.449 -0.818 0.42 36.65 s ANISOU 1101 OE1 GLN A 287 2397 3873 3896 -487 -15 -523 o ANISOU 1146 SG BCYS A 292 5369 3413 5143 362 -178 -181 s ATOM 1102 NE2 GLN A 287 -2.616 48.440 -2.837 1.00 27.30 N ATOM 1147 N ARG A 293 -8.418 41.348 2.892 1.00 23.70 N ANISOU 1102 NE2 GLN A 287 2107 4285 3980 -243 -51 -592 N ANISOU 1147 N ARG A 293 3276 2607 3122 935 -622 474 N ATOM 1103 C GLN A 287 -6.777 45.542 -3.438 1.00 23.58 c ATOM 1148 C ARG A 293 -8.050 42.153 5.231 1.00 23.90 ANISOU 1103 C GLN A 287 2648 3042 3268 138 -312 -216 c ANISOU 1148 C ARG A 293 3148 3253 2680 863 -912 648 ATOM 1104 O GLN A 287 -7.348 45.634 -2.345 1.00 24.31 o ATOM 1149 O ARG A 293 -8.215 41.823 6.410 1.00 26.07 o ANISOU 1104 O GLN A 287 2807 3062 3366 88 -405 -173 o ANISOU 1149 O ARG A 293 3493 3668 2744 972 -960 844 o ATOM 1105 N ALA A 288 -7.295 44.833 -4.431 1.00 21.19 N ATOM 1150 CA AARG A 293 -7.715 41.123 4.157 0.50 28.76 c ANISOU 1105 N ALA A 288 2484 2668 2899 169 -258 -252 N ANISOU 1150 CA AARG A 293 3776 3601 3552 1158 -749 727 ATOM 1106 CA ALA A 288 -8.462 43.974 -4.186 1.00 19.98 c ATOM 1151 CB AARG A 293 -6.220 41.156 3.918 0.50 29.57 ANISOU 1106 CA ALA A 288 2537 2331 2722 153 -305 -268 c ANISOU 1151 CB AARG A 293 3495 4140 3600 1345 -850 798 ATOM 1107 CB ALA A 288 -8.871 43.253 -5.462 1.00 21.80 c ATOM 1152 CG AARG A 293 -5.647 39.789 3.818 0.50 45.43 ANISOU 1107 CB ALA A 288 2865 2584 2833 87 -205 -419 c ANISOU 1152 CG AARG A 293 5494 5984 5784 1686 -641 1027 ATOM 1108 C ALA A 288 -8.122 42.939 -3.085 1.00 22.48 c ATOM 1153 CD AARG A 293 -4.313 39.750 4.500 0.50 56.11 ANISOU 1108 C ALA A 288 2916 2492 3134 350 -324 -244 c ANISOU 1153 CD AARG A 293 6486 7862 6972 1832 -779 1208 ATOM 1109 O ALA A 288 -8.914 42.665 -2.175 1.00 24.69 o ATOM 1154 NE AARG A 293 -3.313 40.477 3.722 0.50 64.85 N ANISOU 1109 O ALA A 288 3326 2617 3440 342 -378 -181 o ANISOU 1154 NE AARG A 293 7271 9263 8106 1744 -871 1041 N ATOM 1110 N LYS A 289 -6.957 42.319 -3.193 1.00 19.61 N ATOM 1155 CZ AARG A 293 -2.573 41.485 4.181 0.50 58.42 ANISOU 1110 N LYS A 289 2451 2168 2833 564 -240 -248 N ANISOU 1155 CZ AARG A 293 6145 8977 7075 1510 -1094 912 ATOM 1111 CA LYS A 289 -6.564 41.332 -2.162 1.00 21.60 c ATOM 1156 NHIAARG A 293 -1.689 42.061 3.370 0.50 43.26 N ANISOU 1111 CA LYS A 289 2714 2318 3175 846 -220 -100 c ANISOU 1156 NHIAARG A 293 3953 7233 5249 1410 -1096 738 N ATOM 1112 CB LYS A 289 -5.241 40.668 -2.536 1.00 27.58 c ATOM 1157 NH2AARG A 293 -2.706 41.916 5.434 0.50 48.44 N ANISOU 1112 CB LYS A 289 3301 3129 4048 1130 -61 -53 c ANISOU 1157 NH2AARG A 293 4852 8044 5507 1340 -1263 916 N ATOM 1113 CG LYS A 289 -5.376 39.556 -3.551 1.00 32.83 c ATOM 1158 CA BARG A 293 -7.717 41.112 4.172 0.50 28.54 C ANISOU 1113 CG LYS A 289 4165 3468 4842 1181 278 -213 c ANISOU 1158 CA BARG A 293 3749 3572 3522 1162 -749 731 C ATOM 1114 CD LYS A 289 -3.985 39.074 -4.032 1.00 37.34 c ATOM 1159 CB BARG A 293 -6.208 41.132 3.979 0.50 30.71 C ANISOU 1114 CD LYS A 289 4540 4076 5573 1459 502 -166 c ANISOU 1159 CB BARG A 293 3637 4297 3736 1357 -854 813 C ATOM 1115 CE LYS A 289 -4.095 37.966 -5.054 1.0045.86 c ATOM 1160 CG BARG A 293 -5.693 40.027 3.113 0.50 38.39 C ANISOU 1115 CE LYS A 289 5850 4779 6797 1460 945 -395 c ANISOU 1160 CG BARG A 293 4608 5003 4975 1634 -611 899 C ATOM 1116 NZ LYS A 289 -2.752 37.600 -5.643 1.00 45.51 N ATOM 1161 CD BARG A 293 -6.010 38.649 3.692 0.5048.55 C ANISOU 1116 NZ LYS A 289 5617 4738 6939 1711 1229 -367 N ANISOU 1161 CD BARG A 293 6096 5980 6372 1834 -379 1113 C ATOM 1117 C LYS A 289 -6.452 41.974 -0.769 1.00 29.57 c ATOM 1162 NE BARG A 293 -5.060 37.673 3.176 0.50 61.22 N ANISOU 1117 C LYS A 289 3603 3540 4092 847 -441 57 c ANISOU 1162 NE BARG A 293 7586 7514 8160 2110 -157 1231 N ATOM 1118 O LYS A 289 -6.889 41.426 0.255 1.00 27.87 o ATOM 1163 CZ BARG A 293 -5.336 36.394 2.934 0.50 65.64 ANISOU 1118 O LYS A 289 3505 3228 3857 966 -471 206 o ANISOU 1163 CZ BARG A 293 8349 7653 8937 2240 199 1280 ATOM 1119 N LEU A 290 -5.810 43.131 -0.732 1.00 26.71 N ATOM 1164 NHIBARG A 293 -4.386 35.590 2.471 0.50 58.47 N ANISOU 1119 N LEU A 290 3003 3485 3662 691 -549 -1 N ANISOU 1164 NHIBARG A 293 7326 6696 8196 2490 440 1404 N ATOM 1120 CA LEU A 290 -5.609 43.829 0.521 1.00 23.66 c ATOM 1165 NH2BARG A 293 -6.551 35.921 3.161 0.50 68.43 N ANISOU 1120 CA LEU A 290 2475 3373 3142 586 -719 34 c ANISOU 1165 NH2BARG A 293 8999 7655 9347 2088 345 1191 N ATOM 1121 CB LEU A 290 -4.632 44.993 0.316 1.00 28.24 c ATOM 1166 N THR A 294 -8.104 43.397 4.820 1.00 23.14 N ANISOU 1121 CB LEU A 290 2744 4280 3708 378 -731 -123 c ANISOU 1166 N THR A 294 2965 3225 2601 494 -939 369 N ATOM 1122 CG LEU A 290 -4.233 45.884 1.491 1.00 34.27 c ATOM 1167 CA THR A 294 -8.306 44.526 5.720 1.00 23.71 C ANISOU 1122 CG LEU A 290 3294 5417 4310 132 -852 -232 c ANISOU 1167 CA THR A 294 3012 3509 2487 137 -983 199 C ATOM 1123 CD1 LEU A 290 -3.648 45.054 2.647 1.00 39.60 c ATOM 1168 CB THR A 294 -8.058 45.852 5.002 1.00 24.41 c

 ANISOU 1258 CD GLN A 306 14169 13244 7573 -339 570 -246 C ANISOU 1303 O LEU A 311 4206 3072 4248 136 -579 371 O ATOM 1259 OE1 GLN A 306 -25.110 41.576 17.690 1.00 98.93 O ATOM 1304 N FLE A 312 -17.059 36.174 1.231 1.00 22.31 N ANISOU 1259 OE1 GLN A 306 14846 14063 8681 -486 872 -366 o ANISOU 1304 N FLE A 312 2970 2186 3322 98 -308 204 N ATOM 1260 NE2 GLN A 306 -23.862 41.433 19.558 1.00 95.02 N ATOM 1305 CA ILE A 312 -16.758 35.049 0.353 1.00 23.57 C ANISOU 1260 NE2 GLN A 306 14787 13838 7477 -309 523 -257 N ANISOU 1305 CA FLE A 312 3005 2245 3706 35 -289 202 C ATOM 1261 C GLN A 306 -22.757 38.154 14.785 1.00 68.32 C ATOM 1306 CB FLE A 312 -18.021 34.471 -0.217 1.00 25.02 C ANISOU 1261 C GLN A 306 11024 9380 5553 -195 326 562 c ANISOU 1306 CB FLE A 312 3110 2553 3843 -35 -103 194 C ATOM 1262 O GLN A 306 -23.966 38.190 14.551 1.00 63.46 o ATOM 1307 CGI FLE A 312 -18.860 33.916 0.930 1.00 31.07 C ANISOU 1262 0 GLN A 306 10370 8778 4965 -379 685 500 o ANISOU 1307 CGI FLE A 312 4017 3344 4444 -92 -42 308 C ATOM 1263 N ASN A 307 -21.937 37.292 14.191 1.00 56.05 N ATOM 1308 CD1 FLE A 312 -20.200 33.372 0.495 1.00 32.02 C ANISOU 1263 N ASN A 307 9461 7627 4209 -92 130 751 N ANISOU 1308 CD1 FLE A 312 4025 3592 4549 -186 178 230 C ATOM 1264 CA ASN A 307 -22.425 36.170 13.380 1.00 58.66 c ATOM 1309 CG2 FLE A 312 -17.687 33.299 -1.168 1.00 29.23 C ANISOU 1264 CA ASN A 307 9758 7736 4793 -203 345 912 c ANISOU 1309 CG2 FLE A 312 3483 2987 4637 -116 -67 142 C ATOM 1265 CB ASN A 307 -23.004 35.045 14.237 1.00 68.96 c ATOM 1310 C FLE A 312 -15.877 35.557 -0.788 1.00 27.65 C ANISOU 1265 CB ASN A 307 11451 8950 5800 -312 617 1182 c ANISOU 1310 C FLE A 312 3390 2694 4422 51 -281 69 C ATOM 1266 CG ASN A 307 -22.011 33.941 14.480 1.00 81.43 c ATOM 1311 O FLE A 312 -16.356 36.148 -1.761 1.00 24.50 O ANISOU 1266 CG ASN A 307 13307 10325 7308 -153 405 1517 c ANISOU 1311 O FLE A 312 2935 2395 3978 71 -141 10 O ATOM 1267 OD1 ASN A 307 -21.976 32.949 13.745 1.00 92.50 o ATOM 1312 N ALA A 313 -14.583 35.397 -0.619 1.00 23.70 N ANISOU 1267 OD1 ASN A 307 14667 11476 9003 -193 492 1658 o ANISOU 1312 N ALA A 313 2854 2027 4125 60 -428 13 N ATOM 1268 ND2 ASN A 307 -21.178 34.111 15.500 1.00 80.70 N ATOM 1313 CA ALA A 313 -13.637 35.934 -1.614 1.00 24.35 C ANISOU 1268 ND2 ASN A 307 13479 10348 6836 48 106 1620 N ANISOU 1313 CA ALA A 313 2817 2013 4421 44 -376 -147 C ATOM 1269 C ASN A 307 -23.490 36.667 12.423 1.00 57.58 c ATOM 1314 CB ALA A 313 -12.417 36.462 -0.967 1.00 28.54 C ANISOU 1269 C ASN A 307 9288 7637 4951 -342 597 675 c ANISOU 1314 CB ALA A 313 3332 2420 5092 80 -526 -272 C ATOM 1270 O ASN A 307 -24.595 36.113 12.339 1.00 55.42 o ATOM 1315 C ALA A 313 -13.276 34.766 -2.529 1.00 28.76 C ANISOU 1270 O ASN A 307 9018 7334 4706 -520 942 668 o ANISOU 1315 C ALA A 313 3223 2487 5218 -35 -351 -195 C ATOM 1271 N ASN A 308 -23.133 37.736 11.730 1.00 52.50 N ATOM 1316 O ALA A 313 -13.185 33.636 -2.063 1.00 27.24 O ANISOU 1271 N ASN A 308 8364 7059 4525 -246 427 464 N ANISOU 1316 0 ALA A 313 3015 2215 5120 -50 -461 -128 O ATOM 1272 CA ASN A 308 -24.075 38.566 11.002 1.00 51.54 c ATOM 1317 N TYR A 314 -13.083 35.038 -3.828 1.00 24.14 N ANISOU 1272 CA ASN A 308 7957 7026 4601 -294 596 217 c ANISOU 1317 N TYR A 314 2543 1908 4721 -80 -188 -307 N ATOM 1273 CB ASN A 308 -23.983 39.972 11.566 1.00 44.59 c ATOM 1318 CA TYR A 314 -12.761 33.964 -4.788 1.00 21.36 C ANISOU 1273 CB ASN A 308 7029 6303 3611 -227 520 5 c ANISOU 1318 CA TYR A 314 2022 1502 4593 -172 -138 -400 C ATOM 1274 CG ASN A 308 -25.271 40.420 12.144 1.00 68.41 c ATOM 1319 CB TYR A 314 -13.976 33.154 -5.203 1.00 25.25 C ANISOU 1274 CG ASN A 308 10031 9476 6485 -350 804 -170 c ANISOU 1319 CB TYR A 314 2468 2156 4970 -206 -49 -350 C ATOM 1275 OD1 ASN A 308 -26.299 39.775 11.944 1.00 78.84 o ATOM 1320 CG TYR A 314 -15.095 34.008 -5.714 1.00 22.95 C ANISOU 1275 OD1 ASN A 308 11317 10794 7844 -485 1067 -177 o ANISOU 1320 CG TYR A 314 2243 2107 4370 -136 83 -324 C ATOM 1276 ND2 ASN A 308 -25.240 41.524 12.884 1.00 71.94 N ATOM 1321 CD1 TYR A 314 -15.961 34.616 -4.823 1.00 26.91 C ANISOU 1276 ND2 ASN A 308 10478 10064 6793 -319 773 -360 N ANISOU 1321 CD1 TYR A 314 2879 2711 4633 -57 55 -207 C ATOM 1277 C ASN A 308 -23.700 38.671 9.546 1.00 38.43 c ATOM 1322 CE1 TYR A 314 -16.994 35.388 -5.258 1.00 28.70 C ANISOU 1277 C ASN A 308 6029 5263 3310 -208 485 175 c ANISOU 1322 CE1 TYR A 314 3146 3151 4606 40 149 -201 C ATOM 1278 O ASN A 308 -24.503 39.025 8.668 1.00 31.35 o ATOM 1323 CZ TYR A 314 -17.171 35.604 -6.616 1.00 28.95 C ANISOU 1278 0 ASN A 308 4901 4413 2596 -213 612 26 o ANISOU 1323 CZ TYR A 314 3119 3314 4567 91 256 -284 C ATOM 1279 N CYS A 309 -22.436 38.403 9.299 1.00 32.05 N ATOM 1324 OH TYR A 314 -18.218 36.401 -6.993 1.00 31.00 O ANISOU 1279 N CYS A 309 5253 4329 2597 -107 232 289 N ANISOU 1324 OH TYR A 314 3432 3793 4553 248 305 -267 O ATOM 1280 CA CYS A 309 -21.873 38.739 8.016 1.00 30.24 c ATOM 1325 CE2 TYR A 314 -16.338 35.017 -7.551 1.00 28.08 C ANISOU 1280 CA CYS A 309 4798 4010 2684 -20 121 223 c ANISOU 1325 CE2 TYR A 314 2899 3129 4642 4 303 -391 C ATOM 1281 CB CYS A 309 -21.243 40.124 8.161 1.00 40.98 c ATOM 1326 CD2 TYR A 314 -15.266 34.229 -7.084 1.00 26.73 C ANISOU 1281 CB CYS A 309 6094 5408 4068 87 -9 58 c ANISOU 1326 CD2 TYR A 314 2656 2719 4783 -125 225 -424 C ATOM 1282 SG CYS A 309 -20.620 40.771 6.675 1.00 43.61 s ATOM 1327 C TYR A 314 -12.033 34.510 -5.984 1.00 32.30 C ANISOU 1282 SG CYS A 309 6210 5613 4749 183 -59 -25 s ANISOU 1327 C TYR A 314 3339 2875 6057 -209 23 -547 C ATOM 1283 C CYS A 309 -20.802 37.714 7.700 1.00 33.97 c ATOM 1328 O TYR A 314 -12.129 35.713 -6.306 1.00 24.86 O ANISOU 1283 C CYS A 309 5314 4306 3288 12 -53 386 c ANISOU 1328 0 TYR A 314 2510 1940 4997 -173 155 -550 O ATOM 1284 0 CYS A 309 -20.087 37.274 8.590 1.00 33.95 o ATOM 1329 N GLN A 315 -11.193 33.657 -6.539 1.00 31.12 N ANISOU 1284 0 CYS A 309 5503 4265 3130 56 -213 506 o ANISOU 1329 N GLN A 315 2353 5936 3534 449 -507 650 N ATOM 1285 N ARG A 310 -20.682 37.332 6.437 1.00 27.49 N ATOM 1330 CA GLN A 315 -10.335 34.001 -7.654 1.00 29.17 C ANISOU 1285 N ARG A 310 4312 3388 2742 10 -35 378 N ANISOU 1330 CA GLN A 315 1998 5780 3306 571 -354 631 C ATOM 1286 CA ARG A 310 -19.639 36.403 6.028 1.00 27.36 c ATOM 1331 CB GLN A 315 -8.960 34.402 -7.146 1.00 31.75 C ANISOU 1286 CA ARG A 310 4292 3193 2912 37 -190 488 c ANISOU 1331 CB GLN A 315 1897 6571 3597 542 -380 844 C ATOM 1287 CB ARG A 310 -20.220 35.011 5.845 1.00 31.43 c ATOM 1332 CG GLN A 315 -8.030 34.958 -8.189 1.00 41.08 C ANISOU 1287 CB ARG A 310 4844 3614 3483 -74 -29 619 c ANISOU 1332 CG GLN A 315 2938 7866 4804 604 -206 814 C ATOM 1288 CG ARG A 310 -19.161 33.962 5.568 1.00 47.33 c ATOM 1333 CD GLN A 315 -6.621 35.126 -7.662 1.00 53.35 C ANISOU 1288 CG ARG A 310 6871 5412 5699 -37 -183 742 c ANISOU 1333 CD GLN A 315 4236 9687 6348 561 -209 1016 C ATOM 1289 CD ARG A 310 -18.592 33.453 6.871 1.00 69.84 c ATOM 1334 OE1 GLN A 315 -6.233 34.519 -6.660 1.00 62.13 O ANISOU 1289 CD ARG A 310 10016 8185 8336 42 -336 942 c ANISOU 1334 OE1 GLN A 315 5239 10917 7451 601 -313 1238 O ATOM 1290 NE ARG A 310 -17.935 32.159 6.714 1.00 89.65 N ATOM 1335 NE2 GLN A 315 -5.840 35.955 -8.336 1.00 72.17 N ANISOU 1290 NE ARG A 310 12580 10452 11032 74 -414 1105 ANISOU 1335 NE2 GLN A 315 6513 12184 8725 476 -96 953 N ATOM 1291 CZ ARG A 310 -18.543 30.988 6.886 1.00 99.47 ι ATOM 1336 C GLN A 315 -10.246 32.720 -8.454 1.00 37.56 C ANISOU 1291 CZ ARG A 310 13965 11542 12287 -23 -196 1280 ANISOU 1336 C GLN A 315 3249 6549 4474 959 -169 672 C ATOM 1292 NH1 ARG A 310 -17.866 29.854 6.726 1.00100.90 ATOM 1337 O GLN A 315 -10.024 31.651 -7.890 1.00 35.66 O ANISOU 1292 NH1 ARG A 310 14193 11466 12680 29 -272 1425 ANISOU 1337 0 GLN A 315 2973 6268 4307 1202 -138 872 O ATOM 1293 ΝΉ2 ARG A 310 -19.829 30.951 7.224 1.00101.33 N ATOM 1338 N GLU A 316 -10.457 32.833 -9.758 1.00 34.53 N ANISOU 1293 NH2 ARG A 310 14286 11859 12355 -178 124 1288 I ANISOU 1338 N GLU A 316 3101 5939 4078 995 -18 484 N ATOM 1294 C ARG A 310 -19.074 36.889 4.688 1.00 25.08 c ATOM 1339 CA GLU A 316 -10.470 31.691 -10.660 1.00 37.57 C ANISOU 1294 C ARG A 310 3776 2848 2905 87 -236 363 c ANISOU 1339 CA GLU A 316 3774 5988 4513 1274 217 449 C ATOM 1295 O ARG A 310 -19.835 37.176 3.778 1.00 26.01 o ATOM 1340 CB GLU A 316 -11.659 31.805 -11.602 1.0043.39 C ANISOU 1295 0 ARG A 310 3754 3040 3090 70 -85 281 o ANISOU 1340 CB GLU A 316 4922 6419 5147 1086 192 167 C ATOM 1296 N LEU A 311 -17.744 36.995 4.588 1.00 28.48 N ATOM 1341 CG GLU A 316 -12.939 32.260 -10.968 1.00 53.58 C ANISOU 1296 N LEU A 311 4175 3161 3486 158 -439 331 N ANISOU 1341 CG GLU A 316 6279 7666 6413 799 -68 71 C ATOM 1297 CA LEU A 311 -17.085 37.403 3.339 1.00 23.32 c ATOM 1342 CD GLU A 316 -14.055 32.388 -12.007 1.00 65.76 C ANISOU 1297 CA LEU A 311 3338 2421 3102 179 -439 214 c ANISOU 1342 CD GLU A 316 8149 8974 7861 621 -116 -140 C ATOM 1298 CB LEU A 311 -15.748 38.080 3.637 1.00 28.59 c ATOM 1343 OE1 GLU A 316 -14.122 31.508 -12.909 1.00 62.88 O ANISOU 1298 CB LEU A 311 3973 3002 3886 247 -619 82 c ANISOU 1343 OE1 GLU A 316 8087 8374 7430 713 36 -236 O ATOM 1299 CG LEU A 311 -15.860 39.295 4.538 1.00 35.69 c ATOM 1344 OE2 GLU A 316 -14.849 33.365 -11.931 1.00 62.69 O ANISOU 1299 CG LEU A 311 4937 4006 4616 290 -630 -29 c ANISOU 1344 OE2 GLU A 316 7717 8643 7460 376 -284 -189 O ATOM 1300 CD1 LEU A 311 -14.510 40.015 4.593 1.00 37.69 c ATOM 1345 C GLU A 316 -9.208 31.693 -11.494 1.00 41.89 C ANISOU 1300 CD1 LEU A 311 5085 4159 5074 333 -760 -246 c ANISOU 1345 C GLU A 316 4180 6627 5109 1501 483 538 C ATOM 1301 CD2 LEU A 311 -16.935 40.205 4.008 1.00 29.42 c ATOM 1346 O GLU A 316 -8.631 32.747 -11.763 1.00 43.79 O ANISOU 1301 CD2 LEU A 311 4122 3293 3764 283 -399 -57 c ANISOU 1346 0 GLU A 316 4205 7125 5310 1374 468 522 O ATOM 1302 C LEU A 311 -16.757 36.143 2.527 1.00 29.04 c ATOM 1347 N PRO A 317 -8.761 30.500 -11.918 1.00 46.74 N ANISOU 1302 C LEU A 311 3971 3020 4043 129 -445 273 c ANISOU 1347 N PRO A 317 4934 6997 5829 1840 787 634 N ATOM 1303 O LEU A 311 -16.204 35.180 3.075 1.00 30.33 o ATOM 1348 CA PRO A 317 -7.609 30.417 -12.813 1.00 48.15 C

 ANISOU 1438 CB VAL A 329 3944 3012 4143 -603 -653 -59 C ANISOU 1483 CG ARG A 334 8612 4709 7496 142 128 364 c ATOM 1439 CGI VAL A 329 -23.641 31.135 -0.998 1.00 35.10 C ATOM 1484 CD ARG A 334 -23.716 22.301 1.879 1.00 58.47 c ANISOU 1439 CGI VAL A 329 4738 3574 5026 -836 -563 -63 C ANISOU 1484 CD ARG A 334 9137 5073 8006 363 230 292 c ATOM 1440 CG2 VAL A 329 -22.068 31.919 -2.727 1.00 25.08 C ATOM 1485 NE ARG A 334 -24.907 21.997 1.090 1.00 53.37 N ANISOU 1440 CG2 VAL A 329 3229 2749 3551 -660 -685 -55 C ANISOU 1485 NE ARG A 334 8380 4386 7511 127 233 -9 N

ATOM 1441 C VAL A 329 -22.141 28.726 -0.603 1.00 28.84 C ATOM 1486 CZ ARG A 334 -24.871 21.562 -0.164 1.00 56.33 C

ANISOU 1441 C VAL A 329 4142 2824 3990 -335 -568 99 C ANISOU 1486 CZ ARG A 334 8807 4709 7888 148 278 -152 c

ATOM 1442 O VAL A 329 -22.217 28.824 0.622 1.00 33.19 O ATOM 1487 NHl ARG A 334 -23.695 21.404 -0.775 1.00 48.14 N

ANISOU 1442 VAL A 329 4734 3382 4495 -441 -541 181 O ANISOU 1487 NHl ARG A 334 7901 3643 6748 417 372 -56 N

ATOM 1443 N LEU A 330 -22.520 27.627 -1.250 1.00 28.62 N ATOM 1488 ΝΉ2 ARG A 334 -26.007 21.292 -0.808 1.00 47.87 N

ANISOU 1443 N LEU A 330 4287 2547 4041 -194 -507 23 N ANISOU 1488 ΝΉ2 ARG A 334 7650 3629 6908 -76 229 -359 N

ATOM 1444 CA LEU A 330 -23.097 26.505 -0.513 1.00 28.99 C ATOM 1489 C ARG A 334 -22.075 24.282 6.164 1.00 75.37

ANISOU 1444 CA LEU A 330 4566 2289 4160 -144 -386 35 C ANISOU 1489 C ARG A 334 10961 8210 9465 59 -179 1037

ATOM 1445 CB LEU A 330 -23.568 25.404 -1.462 1.00 33.47 C ATOM 1490 O ARG A 334 -21.314 23.310 6.226 1.00 73.23 O

ANISOU 1445 CB LEU A 330 5350 2565 4804 -69 -283 -111 C ANISOU 1490 O ARG A 334 10684 7996 9143 418 -138 1304

ATOM 1446 CG LEU A 330 -24.898 25.699 -2.148 1.00 33.79 C ATOM 1491 N GLN A 335 -22.066 25.287 7.043 1.00 82.10 N ANISOU 1446 CG LEU A 330 5389 2462 4987 -357 -342 -311 C ANISOU 1491 N GLN A 335 11779 9287 10129 -282 -281 1045 N ATOM 1447 CD1 LEU A 330 -25.147 24.664 -3.247 1.00 32.28 C ATOM 1492 CA GLN A 335 -21.179 25.311 8.207 1.00 87.81 C ANISOU 1447 CD1 LEU A 330 5358 2136 4772 -339 -242 -464 C ANISOU 1492 CA GLN A 335 12461 10394 10508 -322 -415 1361 ATOM 1448 CD2 LEU A 330 -26.029 25.637 -1.100 1.00 33.43 C ATOM 1493 CB GLN A 335 -19.723 25.282 7.761 1.00 87.61 C ANISOU 1448 CD2 LEU A 330 5203 2429 5069 -476 -174 -307 C ANISOU 1493 CB GLN A 335 12085 10862 10339 -64 -609 1637 C

ATOM 1449 C LEU A 330 -22.106 25.926 0.509 1.00 40.33 C ATOM 1494 CG GLN A 335 -19.219 26.618 7.293 1.00 87.85 C

ANISOU 1449 C LEU A 330 6015 3854 5457 82 -339 280 C ANISOU 1494 CG GLN A 335 11852 11255 10271 -330 -765 1507

ATOM 1450 O LEU A 330 -22.501 25.497 1.603 1.00 38.52 O ATOM 1495 CD GLN A 335 -17.801 26.526 6.793 1.00100.41 C

ANISOU 1450 O LEU A 330 5923 3476 5234 47 -273 353 O ANISOU 1495 CD GLN A 335 13072 13311 11768 -59 -928 1783 (

ATOM 1451 N ARG A 331 -20.829 25.890 0.138 1.00 34.46 N ATOM 1496 OE1 GLN A 335 -17.369 27.322 5.953 1.00 97.19 O

ANISOU 1451 N ARG A 331 5114 3391 4591 318 -368 435 N ANISOU 1496 OE1 GLN A 335 12442 13096 11390 -124 -990 1657

ATOM 1452 CA ARG A 331 -19.789 25.511 1.088 1.00 43.92 C ATOM 1497 NE2 GLN A 335 -17.058 25.540 7.302 1.00106.17 N ANISOU 1452 CA ARG A 331 6213 4825 5649 526 -378 750 C ANISOU 1497 NE2 GLN A 335 13716 14216 12405 270 -971 2194

ATOM 1453 CB ARG A 331 -18.427 25.754 0.488 1.00 48.86 C ATOM 1498 C GLN A 335 -21.395 26.541 9.093 1.00 86.69 C ANISOU 1453 CB ARG A 331 6566 5811 6188 739 -427 914 C ANISOU 1498 C GLN A 335 12375 10417 10147 -832 -462 1256 C

ATOM 1454 CG ARG A 331 -17.656 24.541 0.224 1.00 66.08 C ATOM 1499 O GLN A 335 -22.446 27.182 9.066 1.00 84.41 O ANISOU 1454 CG ARG A 331 8778 7910 8420 1170 -240 1135 C ANISOU 1499 O GLN A 335 12232 9813 10028 -1111 -302 969 O

ATOM 1455 CD ARG A 331 -16.339 24.980 -0.310 1.00 72.85 C TER 1500 GLN A 335

ANISOU 1455 CD ARG A 331 9306 9155 9219 1338 -290 1306 C HET ATM 1501 OAD DRG B 1 -16.913 52.085 3.644 1.00 21.87 O

ATOM 1456 NE ARG A 331 -16.178 24.508 -1.670 1.00 79.52 N HET ATM 1502 CAQ DRG B 1 -18.087 52.173 3.207 1.00 18.29 C ANISOU 1456 NE ARG A 331 10270 9768 10177 1538 -72 1171 N HET ATM 1503 CAS DRG B 1 -19.156 52.069 -4.081 1.00 18.47 C

ATOM 1457 CZ ARG A 331 -15.371 23.507 -1.997 1.00 87.77 C HET ATM 1504 CAJ DRG I -18.968 51.880 - 5.449 1.00 19.15 C ANISOU 1457 CZ ARG A 331 11325 10712 11312 1951 192 1392 C HET ATM 1505 CAH DRG -20.089 51.757 6.304 1.00 16.84 C ATOM 1458 NHl ARG A 331 -14.649 22.919 -1.050 1.00 82.48 N HET ATM 1506 CAN DRG -21.395 51.829 5.799 1.00 19.67 C ANISOU 1458 NHl ARG A 331 10488 10201 10648 2237 224 1809 N HET ATM 1507 CAA DRG -22.520 51.711 6.653 1.00 25.26 C ATOM 1459 NH2 ARG A 331 -15.269 23.110 -3.263 1.00 94.50 N HET ATM 1508 CAO DRG 21.592 52.036 -4.427 1.00 22.20 C ANISOU 1459 NH2 ARG A 331 12356 11309 12241 2075 442 1223 N HET ATM 1509 CAB DRG 22.866 52.116 -3.794 1.00 19.46 C

ATOM 1460 C ARG A 331 -19.869 26.326 2.382 1.00 50.48 C HET ATM 1510 CAT DRG -20.465 52.177 -3.620 1.00 21.40 C

ANISOU 1460 C ARG A 331 6971 5871 6336 245 -510 832 C HET ATM 1511 OAL DRG B -20.706 52.339 -2.325 1.00 22.41 O

ATOM 1461 O ARG A 331 -19.793 25.779 3.483 1.00 50.95 O HET ATM 1512 CAU DRG : -19.692 52.388 -1.437 1.00 22.13 C ANISOU 1461 O ARG A 331 7122 5932 6307 290 -494 1026 O HET ATM 1513 CAR DRG : -18.353 52.319 -1.857 1.00 15.64 C ATOM 1462 N HIS A 332 -20.003 27.640 2.247 1.00 47.45 N HET ATM 1514 CAI DRG E -17.334 52.372■ 0.879 1.00 22.69 C

ANISOU 1462 N HIS A 332 6455 5661 5914 -59 -608 691 N HET ATM 1515 CAF DRG I -17.712 52.519 0.460 1.00 18.38 C

ATOM 1463 CA HIS A 332 -20.064 28.505 3.422 1.0048.11 C HET ATM 1516 C AG DRG : -19.054 52.618 0.841 1.00 21.40 C

ANISOU 1463 CA HIS A 332 6525 5919 5835 -394 -667 724 C HET ATM 1517 CAP DRG I -20.066 52.548 -0.115 1.00 21.65 C

ATOM 1464 CB HIS A 332 -19.932 29.970 3.030 1.00 39.01 C HET ATM 1518 CAK DRG : -21.433 52.639 0.231 1.00 25.61 C

ANISOU 1464 CB HIS A 332 5209 4969 4643 -677 -709 581 C HET ATM 1519 CAM DRG -22.368 51.413 -0.084 1.00 32.80 C

ATOM 1465 CG HIS A 332 -18.555 30.363 2.662 1.0043.71 C HET ATM 1520 OAE DRG : -21.857 50.326 -0.472 1.00 22.31 O

ANISOU 1465 CG HIS A 332 5519 6021 5067 -596 -836 716 C HET ATM 1521 OAC DRG : -23.600 51.605 0.140 1.00 24.49 O

ATOM 1466 NDl HIS A 332 -17.677 30.932 3.573 1.00 43.01 N HET ATM 1523 O HOH S 1 -28.626 34.785 4.215 1.00 27.03 O ANISOU 1466 NDl HIS A 332 5287 6358 4698 -816 -951 867 N HET ATM 1524 HOH S 2 -47.650 29.425 8.056 1.00 26.56 O

ATOM 1467 CE1 HIS A 332 -16.535 31.187 2.964 1.00 46.31 C HET ATM 1525 HOH S 3 -24.245 53.450 2.078 1.00 23.35 O ANISOU 1467 CE1 HIS A 332 5413 7140 5041 -698 -1047 972 C HET ATM 1526 HOH S 4 -12.178 44.652 ■8.731 1.00 28.37 O

ATOM 1468 NE2 HIS A 332 -16.623 30.797 1.705 1.0042.72 N HET ATM 1527 HOH S 5 -24.927 42.673 ■5.489 1.00 28.51 O

ANISOU 1468 NE2 HB A 332 4945 6487 4801 -396 -975 892 N HET ATM 1528 HOH S 6 -23.646 48.402 ■0.574 1.00 26.00 O

ATOM 1469 CD2 HIS A 332 -17.882 30.271 1.489 1.00 43.95 C HET ATM 1529 HOH S 7 -22.287 45.745 ■0.729 1.00 29.09 O ANISOU 1469 CD2 HIS A 332 5377 6163 5158 -349 -858 727 C HET ATM 1530 HOH S 8 31.590 54.969 11.707 1.00 29.64 O ATOM 1470 C HB A 332 -21.368 28.329 4.173 1.00 48.81 C HET ATM 1531 HOH S 9 28.418 41.765 -0.998 1.00 31.77 O

ANISOU 1470 C HIS A 332 6891 5617 6040 -588 -535 603 C HET ATM 1532 HOH S 10 -30.530 45.924 8.039 1.00 29.84 O

ATOM 1471 O HIS A 332 -21.416 28.396 5.398 1.00 51.44 O HET ATM 1533 HOH S 11 -33.319 26.230 0.957 1.00 29.84 O

ANISOU 1471 O HIS A 332 7339 5992 6214 -767 -522 694 O HET ATM 1534 HOH S 12 -35.646 26.330 5.040 1.00 34.11 O

ATOM 1472 N LEU A 333 -22.438 28.126 3.426 1.00 39.92 N HET ATM 1535 HOH S 13 -34.846 44.984 0.897 1.00 29.86 O

ANISOU 1472 N LEU A 333 5866 4123 5179 -582 -437 404 N HET ATM 1536 HOH S 14 -27.499 41.332 -4.679 1.00 28.34 O

ATOM 1473 CA LEU A 333 -23.730 27.960 4.049 1.00 44.01 C HET ATM 1537 HOH S 15 -45.238 30.820 6.608 1.00 43.53 O ANISOU 1473 CA LEU A 333 6600 4258 5866 -761 -290 295 C HET ATM 1538 HOH S 16 -28.702 41.986 12.955 1.00 37.06 O

ATOM 1474 CB LEU A 333 -24.798 27.797 2.990 1.0043.50 C HET ATM 1539 HOH S 17 -31.558 42.751 14.241 1.00 35.37 O

ANISOU 1474 CB LEU A 333 6496 3947 6084 -737 -223 99 C HET ATM 1540 HOH S 18 -24.593 24.298 -7.345 1.00 34.03 O

ATOM 1475 CG LEU A 333 -25.796 28.932 2.854 1.00 51.50 C HET ATM 1541 HOH S 19 -8.656 59.398 -16.700 1.00 36.28 O

ANISOU 1475 CG LEU A 333 7177 5114 7278 -810 -73 -40 C HET ATM 1542 HOH S 20 -13.395 34.463 1.907 1.00 44.34 O

ATOM 1476 CD1 LEU A 333 -25.136 30.243 3.047 1.00 62.55 C HET ATM 1543 HOH S 21 -40.903 35.861 0.075 1.00 42.86 O

ANISOU 1476 CD1 LEU A 333 8501 6724 8542 -953 -116 -7 C HET ATM 1544 HOH S 22 -30.129 28.153 3.170 1.00 34.09 O

ATOM 1477 CD2 LEU A 333 -26.388 28.887 1.480 1.00 46.78 C HET ATM 1545 HOH S 23 -12.878 28.829 -13.442 1.00 47.21 O ANISOU 1477 CD2 LEU A 333 6480 4543 6752 -755 -29 -153 C HET ATM 1546 HOH S 24 -41.253 37.066 3.047 1.00 36.72 O

ATOM 1478 C LEU A 333 -23.711 26.723 4.919 1.00 52.19 C HET ATM 1547 HOH S 25 1.987 48.116 -11.341 1.00 46.52 O

ANISOU 1478 C LEU A 333 7853 5136 6839 -599 -214 435 C HET ATM 1548 HOH S 26 -9.801 45.800 -13.365 1.00 49.67 O

ATOM 1479 O LEU A 333 -24.203 26.722 6.042 1.00 59.27 O HET ATM 1549 HOH S 27 -20.039 30.304 -11.343 1.00 46.35 O

ANISOU 1479 LEU A 333 8930 5895 7697 -774 -117 459 O HET ATM 1550 HOH S 28 -0.095 44.565 -0.710 1.00 39.19 O

ATOM 1480 N ARG A 334 -23.131 25.663 4.382 1.00 50.19 N HET ATM 1551 HOH S 29 -0.804 42.091 -8.287 1.00 33.98 O

ANISOU 1480 N ARG A 334 7610 4879 6580 -255 -215 537 N HET ATM 1552 HOH S 30 -13.241 42.472 -8.951 1.00 33.71 O

ATOM 1481 CA ARG A 334 -23.110 24.374 5.047 1.00 63.41 C HET ATM 1553 HOH S 31 -41.235 40.094 3.813 1.00 48.03 O

ANISOU 1481 CA ARG A 334 9504 6352 8237 -33 -85 696 C HET ATM 1554 HOH S 33 -16.015 36.319 7.016 1.00 41.21 O

ATOM 1482 CB ARG A 334 -22.873 23.277 4.019 1.00 58.91 C HET ATM 1555 HOH S 34 -20.404 23.105 -2.297 1.00 47.69 O

ANISOU 1482 CB ARG A 334 8999 5600 7785 299 33 686 C HET ATM 1556 HOH S 35 -2.053 42.697 -1.666 1.00 34.78 O

ATOM 1483 CG ARG A 334 -24.070 23.092 3.119 1.00 54.79 C HET ATM 1557 HOH S 36 -39.542 41.578 -3.465 1.00 35.79 O ΗΕΤΑΤΜ 1558 0 HOH S 37 -17.528 50.479 11.644 1.00 45.34 O HETATM 1608 O HOH S 87 -29.289 25.588 3.450 1.00 58.12 o

HETATM 1559 0 HOH S 38 -2.790 36.224 7.911 1.0042.91 o HETATM 1609 O HOH S 88 -27.435 36.764 12.898 1.00 54.77 o

HETATM 1560 0 HOH S 39 -40.194 28.680 -2.146 1.00 39.59 o HETATM 1610 O HOH S 89 -39.441 47.478 6.524 1.00 52.37 o

HETATM 1561 0 HOH S 40 -38.407 41.038 13.382 1.00 42.80 o HETATM 1611 O HOH S 90 -28.782 30.517 9.098 1.00 60.43 o

HETATM 1562 0 HOH S 41 -22.915 26.393 10.704 1.00 51.77 o HETATM 1612 O HOH S 91 -25.426 31.438 10.148 1.00 61.49 o

HETATM 1563 0 HOH S 42 -38.845 41.788 -5.971 1.00 49.03 o HETATM 1613 O HOH S 92 -33.527 37.427 -12.120 1.00 49.18 o

HETATM 1564 0 HOH S 43 -36.099 50.115 9.037 1.00 41.25 o HETATM 1614 O HOH S 93 -6.868 50.707 - 18.505 1.00 50.15 o

HETATM 1565 0 HOH S 44 -17.355 45.376 13.697 1.00 44.10 o HETATM 1615 O HOH S 94 -35.352 21.726 -2.285 1 .00 61.43 o

HETATM 1566 0 HOH S 45 -1.162 40.678 6.005 1.00 39.09 o HETATM 1616 O HOH S 95 -15.812 25.105 4.715 1.00 63.37 o

HETATM 1567 0 HOH S 46 -28.753 22.369 10.777 1.00 55.50 o HETATM 1617 O HOH S 96 -29.866 61.685 9.944 1.00 65.49 o

HETATM 1568 0 HOH S 47 -0.975 52.746 7.990 1.0046.39 o HETATM 1618 O HOH S 97 -27.164 42.367 -8.980 1.00 48.83 o

HETATM 1569 0 HOH S 48 -0.894 40.925 3.330 1.00 51.81 o HETATM 1619 O HOH S 98 -18.982 36.563 -9.603 1.00 29.51 o

HETATM 1570 0 HOH S 49 -38.793 44.872 0.338 1.00 48.00 o HETATM 1620 O HOH S 99 -11.189 32.358 - -16.167 1.00 32.70 o

HETATM 1571 0 HOH S 50 -4.562 44.866 5.976 1.0044.49 o HETATM 1621 O HOH S 100 -10.913 22.271 -12.926 1.00 68.19 o

HETATM 1572 0 HOH S 51 -8.838 52.510 - 19.877 1 .00 48.90 o HETATM 1622 O HOH S 101 -28.185 47.430 0.578 1.00 38.10 o

HETATM 1573 0 HOH S 52 -3.172 41.183 0.843 1.00 32.; o HETATM 1623 O HOH S 102 -35.456 47.332 10.106 1.00 56.92 o

HETATM 1574 0 HOH S 53 -39.600 39.040 -6.706 1 .00 44.50 o HETATM 1624 O HOH S 103 -17.914 47.101 -11.833 1.00 43.20 o

HETATM 1575 0 HOH S 54 -25.008 47.181 -2.438 1.00 54.96 o HETATM 1625 O HOH S 104 -0.497 48.708 -0.679 1.00 42.44 o

HETATM 1576 0 HOH S 55 -41.565 36.148 -3.772 1.00 49.33 o HETATM 1626 O HOH S 105 -3.385 38.402 0.448 1.00 46.11 o

HETATM 1577 0 HOH S 56 -16.996 30.410 -13.718 ] .00 49.44 o HETATM 1627 O HOH S 106 -5.480 37.289 -0.956 1.00 56.81 o

HETATM 1578 0 HOH S 57 -0.606 40.376 - 10.330 1.00 47.80 o HETATM 1628 O HOH S 107 -39.368 34.378 11.707 1.00 45.98 o

HETATM 1579 0 HOH S 58 -34.434 26.234 7.374 1.00 53.47 o HETATM 1629 O HOH S 108 -7.993 44.416 - 14.099 1.00 57.03 o

HETATM 1580 0 HOH S 59 -35.799 24.448 0.839 1.00 54.83 o HETATM 1630 O HOH S 109 -26.188 21.362 -10.628 1.00 50.15 o

HETATM 1581 0 HOH S 60 -4.278 32.309 - 13.316 1.00 54.95 o HETATM 1631 O HOH S 110 -7.070 53.352 - 21.857 1.00 51.73 o

HETATM 1582 0 HOH S 61 -32.854 27.376 3.585 1.00 57.52 o HETATM 1632 O HOH S 111 -27.759 45.038 -2.135 1.00 52.15 o

HETATM 1583 0 HOH S 62 -29.653 39.466 -9.483 1.00 30.72 o HETATM 1633 O HOH S 112 -45.575 33.318 11.373 1.00 54.88 o

HETATM 1584 0 HOH S 63 -38.448 44.245 9.663 1.00 41.03 o HETATM 1634 O HOH S 113 -40.213 41.041 I .415 .00 56.13 o

HETATM 1585 0 HOH S 64 -12.664 36.441 -9.105 1.00 34.86 o HETATM 1635 O HOH S 114 -24.062 22.286 -9.305 .00 56.30 o

HETATM 1586 0 HOH S 65 -26.130 31.681 7.764 1.00 52.31 o HETATM 1636 O HOH S 115 -29.751 62.184 3.214 .00 59.44 o

HETATM 1587 0 HOH S 66 -7.106 38.900 6.887 1.00 53.76 o HETATM 1637 O HOH S 116 -36.144 21.864 -4.757 .00 66.85 o

HETATM 1588 0 HOH S 67 -5.686 44.678 8.679 1.00 53.91 o HETATM 1638 O HOH S 117 -14.039 32.204 0.301 .00 53.76 o

HETATM 1589 0 HOH S 68 -5.310 50.083 - 15.622 1.00 48.56 o HETATM 1639 O HOH S 118 -4.451 41.510 - 15.804 .00 56.62 o

HETATM 1590 0 HOH S 69 -12.151 44.755 -11.201 1.00 52.71 o HETATM 1640 O HOH S 119 -40.947 31.934 -2.395 .00 51.83 o

HETATM 1591 0 HOH S 70 -32.153 39.882 -10.835 1.00 52.92 o HETATM 1641 O HOH S 120 -2.530 52.445 -3.131 1.00 32.81 o

HETATM 1592 0 HOH S 71 -40.912 45.254 8.515 1.00 57.89 o HETATM 1643 O HOH S 122 -18.008 51.050 14.806 1.00 46.96 o

HETATM 1593 0 HOH S 72 -2.684 33.749 - 15.633 1.00 73.29 o HETATM 1644 O HOH S 123 -29.579 48.175 10.569 1.00 36.92 o

HETATM 1594 0 HOH S 73 -36.012 52.047 11.245 1.00 52.92 o HETATM 1645 O HOH S 124 -30.555 50.195 12.051 1.00 43.32 o

HETATM 1595 0 HOH S 74 -0.858 48.085 -5.158 1.0040.90 o HETATM 1646 O HOH S 125 -35.450 33.626 I I .031 1.00 35.19 o

HETATM 1596 0 HOH S 75 -21.507 55.180 10.249 1.00 38.22 o HETATM 1647 O HOH S 126 -33.049 36.196 11.934 1.00 54.98 o

HETATM 1597 0 HOH S 76 -29.020 37.926 11.432 1.00 58.69 o HETATM 1648 O HOH S 127 -42.986 29.868 -1.137 1.00 53.56 o

HETATM 1598 0 HOH S 77 -36.997 40.484 15.741 1.00 54.77 o HETATM 1649 O HOH S 128 -32.867 34.876 -11.501 1.00 34.67 o

HETATM 1599 0 HOH S 78 -7.288 40.043 - 12.107 1.00 46.19 o HETATM 1650 O HOH S 129 -29.358 32.427 -13.212 1.00 34.76 o

HETATM 1600 0 HOH S 79 -39.134 51.613 3.883 1.00 60.09 o HETATM 1651 O HOH S 130 -40.317 46.851 2.832 ..00 48.74 o

HETATM 1601 0 HOH S 80 -29.823 60.093 I.452 1.00 41.05 o HETATM 1653 O HOH S 132 -23.707 45.060 -4.522 1.00 44.38 o

HETATM 1602 0 HOH S 81 -6.828 60.448 -9.582 1.00 38.94 o HETATM 1654 O HOH S 133 -5.646 53.727 - 14.252 1.00 35.34 o

HETATM 1603 0 HOH S 82 -20.347 50.897 -10.447 1.00 41.52 o HETATM 1655 O HOH S 135 -9.150 37.201 1.775 .00 50.25 o

HETATM 1604 0 HOH S 83 -20.453 38.061 I I .698 1.00 52.10 o HETATM 1656 O HOH S 136 -22.113 30.881 7.444 .00 58.42 o

HETATM 1605 0 HOH S 84 -9.000 38.961 - 14.050 1.00 55.93 o HETATM 1659 O HOH S 138 -7.204 46.240 9.573 .00 30.00 o

HETATM 1606 0 HOH S 85 -13.476 38.546 10.079 1.00 45.40 o HETATM 1660 O HOH S 139 -38.441 50.149 7.696 .00 30.00 o

HETATM 1607 0 HOH S 86 -1.261 50.399 -5.536 1.00 51.75 o END

Table 7. DMXAA-hSTING⁰²³⁰¹ complex REMARK 3 T13: -0.0564 T23: -0.0648

REMARK 3 L TENSOR

REMARK 3 Ll l : 0.5884 L22: 3.2436

REMARK 3 L33: 1.0127 L12: -0.3808

REMARK 3 REMARK 3 L13: 0.0492 L23: 1.3981

REMARK 3 REFINEMENT. REMARK 3 S TENSOR

REMARK 3 PROGRAM : PHENIX (phenix.refme: 1.8.2 1309) REMARK 3 Sl l ■0.0732 S12: -0.1629 S13: 0.0759

REMARK 3 AUTHORS : Adams,Afonine,Burnley,Chen,Davis,Echols,Gildea, REMARK 3 S21 ■0.2078 S22: 0.5745 S23: -0.8923

REMARK 3 : Gopal,Gros,Grosse-Kunstleve,Headd,Hung,Immormino, REMARK 3 S31 0.5100 S32: 0.4198 S33: -0.2551

REMARK 3 : Ioerger,McCoy,McKee,Moriarty,Pai,Read,Richardson, REMARK 3 TLS GROUP : 2

REMARK 3 : Richardson,Romo,Sacchettini,Sauter,Smith,Storoni, REMARK 3 SELECTION: chain Ά' and (resid 185 through 203 )

REMARK 3 : Terwilliger,Zwart REMARK 3 ORIGIN FOR THE GROUP (A): 15.0533 -97.1915 -72.8326

REMARK 3 REMARK 3 T TENSOR

REMARK 3 REFINEMENT TARGET : ML REMARK 3 Ti l 0.4444 T22 0.4429

REMARK 3 REMARK 3 T33 0.7942 T12 0.0775

REMARK 3 DATA USED IN REFINEMENT. REMARK 3 T13 0.1063 T23 -0.1346

REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.510 REMARK 3

REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 78.660 REMARK 3 Ll l 1.3482 L22 3.5737

REMARK 3 MIN(FOBS/SIGMA FOBS) : 1.39 REMARK 3 L33 1.1882 L12 -0.3929

REMARK 3 COMPLETENESS FOR RANGE (%) : 94.13 REMARK 3 L13 0.5508 L23 0.1118

REMARK 3 NUMBER OF REFLECTIONS : 14320 REMARK 3 S TENSOR

REMARK 3 NUMBER OF REFLECTIONS (NON-ANOMALOUS) : 14320 REMARK 3 Sl l : -0.1754 S12: 0.1904 S13: -0.9845

REMARK 3 REMARK 3 S21 : -0.1476 S22: -0.0773 S23: -0.9503

REMARK 3 FLT TO DATA USED IN REFINEMENT. REMARK 3 S31 : 0.5475 S32: -0.1593 S33: 0.2662

REMARK 3 R VALUE (WORKTNG + TEST SET) : 0.1995 REMARK 3 TLS GROUP : 3

REMARK 3 R VALUE (WORKING SET) : 0.1975 REMARK 3 SELECTION: chain Ά' and (resid 204 through 218 )

REMARK 3 FREE R VALUE : 0.2391 REMARK 3 ORIGIN FOR THE GROUP (A): -0.0262 -86.6210 -74.0738

REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.03 REMARK 3 T TENSOR

REMARK 3 FREE R VALUE TEST SET COUNT : 720 REMARK 3 Ti l 0.4134 T22 0.5352

REMARK 3 REMARK 3 T33 1.1526 T12 0.0870

REMARK 3 FLT TO DATA USED IN REFINEMENT (IN BINS). REMARK 3 T13 0.0015 T23 0.0352

REMARK 3 BIN RESOLUTION RANGE COMPL. NWORK NFREE RWORK REMARK 3

RFREE REMARK 3 Ll l 0.3197 L22 2.3847

REMARK 3 1 78.6985 - 4.2921 0.95 2803 147 0.1705 0.1929 REMARK 3 L33 1.9616 L12 -0.7523

REMARK 3 2 4.2921 - 3.4068 0.95 2763 123 0.1804 0.2261 REMARK 3 L13 -0.2715 L23 1.7058

REMARK 3 3 3.4068 - 2.9761 0.93 2678 149 0.2266 0.2915 REMARK 3 S TENSOR

REMARK 3 4 2.9761 - 2.7040 0.94 2706 156 0.2615 0.3201 REMARK 3 Sl l : -0.1620 S12: 0.0679 S13: -1.4908

REMARK 3 5 2.7040 - 2.5102 0.92 2650 145 0.2906 0.3356 REMARK 3 S21 : -0.4128 S22: -0.4686 S23: 2.4070

REMARK 3 REMARK 3 S31 : 0.1596 S32: -0.0763 S33: 0.3138

REMARK 3 BULK SOLVENT MODELLING. REMARK 3 TLS GROUP : 4

REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL REMARK 3 SELECTION: chain Ά' and (resid 219 through 247 )

REMARK 3 SOLVENT RADIUS : 1.11 REMARK 3 ORIGIN FOR THE GROUP (A): 12.4963 -92.7353 -62.3817

REMARK 3 SHRINKAGE RADIUS : 0.90 REMARK 3 T TENSOR

REMARK 3 GRID STEP FACTOR : 4.00 REMARK 3 Ti l 0.6214 T22 0.4812

REMARK 3 REMARK 3 T33 0.6515 T12 0.0930

REMARK 3 ERROR ESTIMATES. REMARK 3 T13 0.0352 T23 0.0210

REMARK 3 COORDINATE ERROR (MAXIMUM -LIKELIHOOD BASED) : 0.38 REMARK 3

REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : REMARK 3 Ll l 2.3340 L22 4.1461

28.36 REMARK 3 L33 4.4152 L12 -1.2271

REMARK 3 REMARK 3 L13 -1.0413 L23 0.0238

REMARK 3 STRUCTURE FACTORS CALCULATION ALGORITHM : FFT REMARK 3 S TENSOR

REMARK 3 REMARK 3 Sl l ■0.1280 S12: -0.6561 S13: -0.2175

REMARK 3 DEVIATIONS FROM IDEAL VALUES. REMARK 3 S21 1.0992 S22: 0.2608 S23: -0.2951

REMARK 3 RMSD MAX COUNT REMARK 3 S31 0.3088 S32: -0.4641 S33: 0.1404

REMARK 3 BOND : 0.007 0.050 3034 REMARK 3 TLS GROUP : 5

REMARK 3 ANGLE : 1.262 16.566 4120 REMARK 3 SELECTION: chain Ά' and (resid 248 through 262 )

REMARK 3 CHIRALITY : 0.081 0.389 446 REMARK 3 ORIGIN FOR THE GROUP (A): 8.4387 -94.2521 -79.3077

REMARK 3 PLANARLTY : 0.005 0.043 544 REMARK 3 T TENSOR

REMARK 3 DIHEDRAL : 20.446 89.486 1142 REMARK 3 Ti l 0.6585 T22 0.4111

REMARK 3 MIN NONBONDED DISTANCE : 2.017 REMARK 3 T33 0.6599 T12 0.1126

REMARK 3 REMARK 3 T13 -0.0693 T23: -0.1355

REMARK 3 MOLPROBLTY STATISTICS. REMARK 3

REMARK 3 ALL-ATOM CLASHSCORE : 14.50 REMARK 3 Ll l 2.0873 L22 1.5403

REMARK 3 RAMACHANDRAN PLOT: REMARK 3 L33 0.4325 L12 0.6038

REMARK 3 OUTLIERS : 0.56 % REMARK 3 L13 0.5988 L23 -0.0328

REMARK 3 ALLOWED : 3.89 % REMARK 3 S TENSOR

REMARK 3 FAVORED : 95.56 % REMARK 3 Sl l 0.1274 S12: 0.2224 S13: -0.5200

REMARK 3 ROTAMER OUTLIERS : 14.15 % REMARK 3 S21 -0.6720 S22: -0.2759 S23: 0.6116

REMARK 3 CBETA DEVIATIONS : 3 REMARK 3 S31 0.0107 S32: 0.0571 S33: -0.0481

REMARK 3 REMARK 3 TLS GROUP : 6

REMARK 3 ATOMIC DISPLACEMENT PARAMETERS. REMARK 3 SELECTION: chain Ά' and (resid 263 through 280 )

REMARK 3 WILSON B : None REMARK 3 ORIGIN FOR THE GROUP (A): -0.0640 -71.1490 -64.7673

REMARK 3 RMS(B ISO OR EQUIVALENT BONDED) : 8.54 REMARK 3 T TENSOR

REMARK 3 ATOMS NUMBER OF ATOMS REMARK 3 Ti l 0.2561 T22 0.3183

REMARK 3 ISO. ANISO. REMARK 3 T33 0.4491 T12 -0.0366

REMARK 3 ALL : 3020 2932 REMARK 3 T13 0.0507 T23 -0.0720

REMARK 3 ALL (NO H) : 3020 2932 REMARK 3

REMARK 3 SOLVENT : 46 0 REMARK 3 Ll l 3.8910 L22: 3.4313

REMARK 3 NON-SOLVENT : 2974 2932 REMARK 3 L33 2.8197 L12: -2.0277

REMARK 3 HYDROGENS : 0 0 REMARK 3 L13 -0.9236 L23: 0.2563

REMARK 3 REMARK 3 S TENSOR

REMARK 3 TLS DETAILS. REMARK 3 Sl l : -0.1066 S12: 0.1651 S13 0.0430

REMARK 3 NUMBER OF TLS GROUPS: 13 REMARK 3 S21 : 0.1833 S22: -0.0732 S23 0.6659

REMARK 3 ORIGIN: CENTER OF MASS REMARK 3 S31 : 0.3945 S32: -0.8557 S33 0.0402

REMARK 3 TLS GROUP : 1 REMARK 3 TLS GROUP : 7

REMARK 3 SELECTION: chain 'A' and (resid 154 through 184 ) REMARK 3 SELECTION: chain Ά' and (resid 281 through 301 )

REMARK 3 ORIGIN FOR THE GROUP (A): 18.5649 -84.9417 -65.0832 REMARK 3 ORIGIN FOR THE GROUP (A): 11.2863 -70.6978 -72.9476

REMARK 3 T TENSOR REMARK 3 T TENSOR

REMARK 3 Ti l : 0.4393 T22: 0.3018 REMARK 3 Ti l : 0.3233 T22: 0.2157

REMARK 3 T33: 0.4398 T12: 0.0825 REMARK 3 T33: 0.3495 T12: 0.0468 REMARK 3 T13 0.0400 T23 0.0147 REMARK T13: -0.0138 T23: -0.0069

REMARK 3 L TENSOR REMARK L TENSOR

REMARK 3 Ll l 8.5718 L22 4.6285 REMARK Ll l : 2.2900 L22: 3.5956

REMARK 3 L33 3.2871 L12 -2.7268 REMARK L33: 3.1007 L12: 0.4476

REMARK 3 L13 1.2567 L23 0.1583 REMARK L13: -0.6791 L23: -1.4882

REMARK 3 S TENSOR REMARK S TENSOR

REMARK 3 Sl l 0.4866 S12 0.3128 S13 1.2110 REMARK 0.1403 S12: 0.7469 S13 0.0186

REMARK 3 S21 -0.5846 S22 -0.2970 S23 -0.6743 REMARK 0.7529 S22: 0.0615 S23 0.0205

REMARK 3 S31 -0.0057 S32 0.0562 S33 -0.0866 REMARK -0.3571 S32: 0.0704 S33 -0.0094

REMARK 3 TLS GROUP : 8 REMARK 3

REMARK 3 SELECTION: chain A' and (resid 302 through 314 ) CRYST1 36.570 77.919 79.634 90.00 .97 90.00 P 1 21 1

REMARK 3 ORIGIN FOR THE GROUP (A) 19.5103 -82.4342 -73.4070 SCALEl 0.027345 0.000000 0.004317 0.00000

REMARK 3 T TENSOR SCALE2 0.000000 0.012834 0.000000 0.00000

REMARK 3 Ti l 0.4366 T22 0.4324 SCALE3 0.000000 0.000000 0.012713 0.00000

REMARK 3 T33 0.9085 T12 -0.0064 ATOM 1 N SER A 154 12.290 -62.777 -65.163 1.00 38.38 N

REMARK 3 T13 -0.0121 T23: -0.1791 ANISOU 1 N SER A 154 4119 4350 6113 -935 208 -285 N

REMARK 3 L TENSOR ATOM 2 CA SER A 154 11.396 -63.506 -66.054 1.00 25.17 C

REMARK 3 Ll l 5.0079 L22 1.4371 ANISOU 2 CA SER A 154 2763 2582 4220 -991 161 -112 C

REMARK 3 L33 2.3589 L12 0.3981 ATOM 3 CB SER A 154 12.123 -63.829 -67.354 1.00 30.71 C

REMARK 3 L13 1.8094 L23 0.5328 ANISOU 3 CB SER A 154 3671 3116 4882 -1071 398 -137 C

REMARK 3 S TENSOR ATOM 4 OG SER A 154 11.332 -64.604 -68.222 1.00 38.95 O

REMARK 3 Sl l -0.2832 S12 -0.0864 S13 1.3536 ANISOU 4 OG SER A 154 5026 4061 5710 -1111 343 16 O

REMARK 3 S21 -0.2094 S22 0.2364 S23 -1.3952 ATOM 5 C SER A 154 10.920 -64.795 -65.403 1.00 36.48 C

REMARK 3 S31 -0.0630 S32 0.4603 S33 -0.1243 ANISOU 5 C SER A 154 4192 4114 5553 -883 -20 -45 C

REMARK 3 TLS GROUP : 9 ATOM 6 O SER A 154 11.686 -65.464 -64.707 1.0040.92 O

REMARK 3 SELECTION: chain A¹ and (resid 315 through 335 ) ANISOU 6 O SER A 154 4592 4763 6193 -768 -27 -147 O

REMARK 3 ORIGIN FOR THE GROUP (A) 5.9841 -84.6983 -84.8320 ATOM 7 N VAL A 155 9.654 -65.141 -65.634 1.00 38.95 N

REMARK 3 T TENSOR ANISOU 7 N VAL A 155 4692 4404 5704 -917 -168 118 N

REMARK 3 Ti l 0.8254 T22 0.4773 ATOM 8 CA VAL A 155 9.066 -66.362 -65.094 1.00 30.23 C

REMARK 3 T33 0.7360 T12 0.0892 ANISOU 8 CA VAL A 155 3619 3370 4498 -838 -323 197 C

REMARK 3 T13 -0.2281 T23: -0.1026 ATOM 9 CB VAL A 155 7.565 -66.467 -65.416 1.00 34.83 C

REMARK 3 L TENSOR ANISOU 9 CB VAL A 155 4383 3908 4945 -903 -477 357 C

REMARK 3 Ll l 0.5859 L22 3.6900 ATOM 10 CGI VAL A 155 7.082 -67.913 -65.299 1.00 26.15 C

REMARK 3 L33 3.4392 L12 0.8135 ANISOU 10 CGI VAL A 155 3391 2817 3729 -855 -571 439 C

REMARK 3 L13 -1.0849 L23 0.4363 ATOM 11 CG2 VAL A 155 6.765 -65.560 -64.508 1.00 17.05 C

REMARK 3 S TENSOR ANISOU 11 CG2 VAL A 155 1968 1754 2755 -901 -610 369 C

REMARK 3 Sl l 0.1659 S12 0.6695 S13 0.4312 ATOM 12 C VAL A 155 9.781 -67.590 -65.652 1.00 22.80 C

REMARK 3 S21 -1.8859 S22 0.0194 S23 0.7650 ANISOU 12 C VAL A 155 2793 2367 3502 -802 -230 175 C

REMARK 3 S31 -1.3287 S32 -0.1047 S33 0.1265 ATOM 13 O VAL A 155 10.131 -68.517 -64.919 1.00 35.79 O

REMARK 3 TLS GROUP : 10 ANISOU 13 O VAL A 155 4350 4095 5154 -688 -288 139 O

REMARK 3 SELECTION: chain 'Β' and (resid 154 through 184 ) ATOM 14 N ALA A 156 9.997 -67.576 -66.960 1.00 21.75 N

REMARK 3 ORIGIN FOR THE GROUP (A) 2.6989 -79.4016 -49.5127 ANISOU 14 N ALA A 156 2877 2081 3307 -895 -85 196 N

REMARK 3 T TENSOR ATOM 15 CA ALA A 156 10.641 -68.677 -67.665 1.00 30.61 C

REMARK 3 Ti l 0.4055 T22 0.5218 ANISOU 15 CA ALA A 156 4137 3123 4369 -877 24 176 C

REMARK 3 T33 0.4268 T12 -0.0439 ATOM 16 CB ALA A 156 10.571 -68.456 -69.164 1.00 42.97 C

REMARK 3 T13 0.0964 T23 0.1163 ANISOU 16 CB ALA A 156 5999 4500 5826 -1001 167 229 C

REMARK 3 L TENSOR ATOM 17 C ALA A 156 12.095 -68.868 -67.247 1.00 39.65 C

REMARK 3 Ll l 0.8467 L22 1.0167 ANISOU 17 C ALA A 156 5066 4319 5682 -792 159 -10 C

REMARK 3 L33 1.5333 L12 0.1082 ATOM 18 O ALA A 156 12.624 -69.982 -67.245 1.00 48.24 O

REMARK 3 L13 0.4092 L23 -0.9415 ANISOU 18 O ALA A 156 6166 5406 6756 -714 173 -50 O

REMARK 3 S TENSOR ATOM 19 N HIS A 157 12.751 -67.764 -66.923 1.00 33.82 N

REMARK 3 Sl l -0.3737 S12 -0.2406 S13 -0.4167 ANISOU 19 N HIS A 157 4124 3612 5116 -806 256 -135 N

REMARK 3 S21 -0.1505 S22 0.5597 S23 -0.1553 ATOM 20 CA HIS A 157 14.158 - 67.781 -66.578 1.00 30.84 C

REMARK 3 S31 0.3988 S32 -0.8521 S33 -0.0941 ANISOU 20 CA HIS A 157 3512 3266 4941 -733 390 -345 C

REMARK 3 TLS GROUP : 11 ATOM 21 CB HIS A 157 14.680 -66.351 -66.440 1.00 44.66 C

REMARK 3 SELECTION: chain 'Β' and (resid 185 through 197 ) ANISOU 21 CB HIS A 157 5077 5016 6877 -792 513 -466 C

REMARK 3 ORIGIN FOR THE GROUP (A) 4.3298 -89.0654 -31.6612 ATOM 22 CG HIS A 157 16.159 - 66.254 -66.244 1.00 41.24 C

REMARK 3 T TENSOR ANISOU 22 CG HIS A 157 4392 4586 6690 -740 679 -708 C

REMARK 3 Ti l 0.8391 T22 0.9093 ATOM 23 NDl HIS A 157 17.059 -66.776 -67.134 1.00 43.00 N

REMARK 3 T33 0.9086 T12 -0.0131 ANISOU 23 NDl HIS A 157 4684 4694 6960 -775 905 -806 N

REMARK 3 T13 0.1673 T23 0.1257 ATOM 24 CE1 HIS A 157 18.292 -66.536 -66.707 1.00 40.67 C

REMARK 3 L TENSOR ANISOU 24 CE1 HIS A 157 4095 4426 6932 -715 1012 -1047 C

REMARK 3 Ll l 0.3021 L22 2.2105 ATOM 25 NE2 HIS A 157 18.214 -65.881 -65.569 1.00 35.86 N

REMARK 3 L33 0.2378 L12 0.5587 ANISOU 25 NE2 HIS A 157 3242 3945 6436 -637 849 -1103 N

REMARK 3 L13 0.0275 L23 0.7643 ATOM 26 CD2 HIS A 157 16.885 -65.684 -65.256 1.00 34.62 C

REMARK 3 S TENSOR ANISOU 26 CD2 HIS A 157 3227 3848 6080 -654 648 -889 C

REMARK 3 Sl l -0.3698 S12 -0.2731 S13 -0.2713 ATOM 27 C HIS A 157 14.386 -68.557 -65.279 1.00 33.45 C

REMARK 3 S21 1.3272 S22 0.5413 S23 -0.7772 ANISOU 27 C HIS A 157 3643 3745 5322 -555 203 -407 C

REMARK 3 S31 -0.2905 S32 -0.6279 S33 -0.0887 ATOM 28 O HIS A 157 15.263 -69.426 -65.196 1.00 36.54 O

REMARK 3 TLS GROUP : 12 ANISOU 28 O HIS A 157 3971 4136 5776 -459 237 -520 O

REMARK 3 SELECTION: chain 'Β' and (resid 198 through 252 ) ATOM 29 N GLY A 158 13.584 -68.249 -64.266 1.00 30.30 N

REMARK 3 ORIGIN FOR THE GROUP (A) 12.7528 -81.7477 -42.9709 ANISOU 29 N GLY A 158 3164 3462 4888 -508 4 -334 N

REMARK 3 T TENSOR ATOM 30 CA GLY A 158 13.659 -68.964 -63.006 1.00 25.57 C

REMARK 3 Ti l 0.6197 T22 0.7199 ANISOU 30 CA GLY A 158 2434 2991 4292 -341 -184 -367 C

REMARK 3 T33 0.5747 T12 0.0259 ATOM 31 C GLY A 158 13.309 -70.431 -63.176 1.00 30.72 C

REMARK 3 T13 -0.0478 T23: 0.1385 ANISOU 31 C GLY A 158 3285 3621 4766 -292 -277 -248 C

REMARK 3 L TENSOR ATOM 32 O GLY A 158 13.948 -71.304 -62.589 1.00 42.20 O

REMARK 3 Ll l 1.7783 L22 3.4469 ANISOU 32 O GLY A 158 4680 5128 6227 -144 -372 -310 O

REMARK 3 L33 1.9528 L12 0.4436 ATOM 33 N LEU A 159 12.288 -70.700 -63.984 1.00 24.37 N

REMARK 3 L13 -0.9387 L23 -1.2119 ANISOU 33 N LEU A 159 2729 2727 3804 -411 -260 -83 N

REMARK 3 S TENSOR ATOM 34 CA LEU A 159 11.844 -72.068 -64.235 1.00 25.17 C

REMARK 3 Sl l 0.0497 S12 -0.4807 S13 -0.8641 ANISOU 34 CA LEU A 159 3030 2791 3741 -385 -342 35 C

REMARK 3 S21 0.2895 S22 -0.1031 S23 -0.6763 ATOM 35 CB LEU A 159 10.560 -72.069 -65.067 1.00 36.37 C

REMARK 3 S31 0.5541 S32 0.3894 S33 0.0559 ANISOU 35 CB LEU A 159 4689 4120 5010 -524 -364 211 C

REMARK 3 TLS GROUP : 13 ATOM 36 CG LEU A 159 9.251 -72.243 -64.293 1.00 35.53 C

REMARK 3 SELECTION: chain 'Β' and (resid 253 through 335 ) ANISOU 36 CG LEU A 159 4631 4067 4802 -530 -546 352 C

REMARK 3 ORIGIN FOR THE GROUP (A) 12.4991 -68.6162 -46.0924 ATOM 37 CD2 LEU A 159 8.069 -71.768 -65.123 1.00 18.32 C

REMARK 3 T TENSOR ANISOU 37 CD2 LEU A 159 2607 1802 2554 -672 -565 466 C

REMARK 3 Ti l 0.3619 T22 0.5606 ATOM 38 CD1 LEU A 159 9.310 -71.503 -62.965 1.00 38.67 C

REMARK 3 T33 0.3032 T12 0.0043 ANISOU 38 CD1 LEU A 159 4804 4608 5280 -452 -641 305 C ATOM 39 C LEU A 159 12.917 -72.905 -64.928 1.00 29.35 C ATOM 84 CZ TYR A 164 23.128 -77.219 -64.385 1.00 58.63 C

ANISOU 39 C LEU A 159 3607 3247 4297 -333 -227 -61 C ANISOU 84 CZ TYR A 164 6096 6777 9404 651 173 -1831 C

ATOM 40 O LEU A 159 13.122 -74.070 -64.587 1.00 35.64 O ATOM 85 OH TYR A 164 24.481 -77.436 -64.264 1.00 64.14 O

ANISOU 40 O LEU A 159 4431 4062 5047 -220 -312 -66 O ANISOU 85 OH TYR A 164 6531 7445 10395 780 209 -2143 O

ATOM 41 N ALA A 160 13.598 -72.306 -65.900 1.00 37.83 N ATOM 86 CE2 TYR A 164 22.563 -76.054 -63.889 1.00 51.96 C

ANISOU 41 N ALA A 160 4701 4226 5446 -420 -23 -142 N ANISOU 86 CE2 TYR A 164 5181 6012 8550 579 139 -1755 C

ATOM 42 CA ALA A 160 14.657 -72.996 -66.627 1.00 31.63 C ATOM 87 CD2 TYR A 164 21.198 -75.860 -64.012 1.00 39.99 C

ANISOU 42 CA ALA A 160 3943 3361 4715 -388 128 -260 C ANISOU 87 CD2 TYR A 164 3913 4519 6762 456 93 -1462 C

ATOM 43 CB ALA A 160 15.168 -72.131 -67.769 1.00 25.03 C ATOM 88 C TYR A 164 18.678 -77.923 -62.655 1.0042.04 C

ANISOU 43 CB ALA A 160 3171 2401 3937 -526 387 -322 C ANISOU 88 C TYR A 164 4715 4866 6392 604 -440 -932 C

ATOM 44 C ALA A 160 15.795 -73.362 -65.683 1.00 34.97 C ATOM 89 O TYR A 164 19.248 -78.997 -62.456 1.00 41.43 O

ANISOU 44 C ALA A 160 4105 3868 5315 -217 89 -457 C ANISOU 89 O TYR A 164 4664 4757 6321 753 -528 -1012 O

ATOM 45 O ALA A 160 16.364 -74.450 -65.764 1.00 30.64 O ATOM 90 N ILE A 165 18.548 -77.000 -61.711 1.00 34.21 N

ANISOU 45 O ALA A 160 3585 3304 4754 -112 53 -506 O ANISOU 90 N FLE A 165 3560 3975 5463 641 -537 -964 N

ATOM 46 N TRP A 161 16.115 -72.437 -64.785 1.00 33.35 N ATOM 91 CA FLE A 165 19.126 -77.164 -60.385 1.00 29.13 C

ANISOU 46 N TRP A 161 3645 3743 5283 -183 84 -584 N ANISOU 91 CA FLE A 165 2761 3407 4900 865 -753 -1106 C

ATOM 47 CA TRP A 161 17.152 -72.645 -63.787 1.00 26.02 C ATOM 92 CB ILE A 165 19.170 -75.821 -59.620 1.00 28.86 C

ANISOU 47 CA TRP A 161 2457 2894 4534 -5 4 -787 C ANISOU 92 CB FLE A 165 2500 3471 4994 868 -791 -1188 C

ATOM 48 CB TRP A 161 17.634 -71.318 -63.223 1.00 35.89 C ATOM 93 CGI FLE A 165 20.057 -74.816 -60.346 1.00 29.74 C

ANISOU 48 CB TRP A 161 3436 4209 5993 -6 36 -935 C ANISOU 93 CGI ILE A 165 2376 3551 5372 769 -568 -1381 C

ATOM 49 CG TRP A 161 18.635 -70.691 -64.132 1.00 43.81 C ATOM 94 CD1 FLE A 165 21.515 -75.304 -60.487 1.00 31.91 C

ANISOU 49 CG TRP A 161 4337 5114 7193 -105 312 -1104 C ANISOU 94 CD1 ILE A 165 2462 3773 5891 903 -531 -1665 C

ATOM 50 CD1 TRP A 161 18.423 -69.712 -65.065 1.00 27.79 C ATOM 95 CG2 FLE A 165 19.674 -76.008 -58.192 1.00 29.77 C

ANISOU 50 CD1 TRP A 161 2394 2998 5168 -294 522 -1056 C ANISOU 95 CG2 ILE A 165 2493 3659 5158 1115 -1046 -1325 C

ATOM 51 NE1 TRP A 161 19.588 -69.438 -65.731 1.00 51.15 N ATOM 96 C FLE A 165 18.376 -78.203 -59.545 1.0041.79 C

ANISOU 51 NE1 TRP A 161 5238 5863 8333 -345 782 -1256 N ANISOU 96 C ILE A 165 4585 5029 6265 982 -975 -944 C

ATOM 52 CE2 TRP A 161 20.580 -70.245 -65.240 1.0044.33 C ATOM 97 O ILE A 165 18.973 -78.957 -58.772 1.00 38.50 O

ANISOU 52 CE2 TRP A 161 4188 5031 7625 -183 731 -1451 C ANISOU 97 O FLE A 165 4157 4613 5860 1192 -1149 -1050 O

ATOM 53 CD2 TRP A 161 20.008 -71.056 -64.239 1.00 38.97 C ATOM 98 N GLY A 166 17.058 -78.239 -59.691 1.00 42.72 N

ANISOU 53 CD2 TRP A 161 3539 4463 6806 -22 425 -1354 C ANISOU 98 N GLY A 166 4911 5151 6171 845 -969 -694 N

ATOM 54 CE3 TRP A 161 20.819 -71.988 -63.576 1.00 38.53 C ATOM 99 CA GLY A 166 16.215 -79.045 -58.830 1.0043.82 C

ANISOU 54 CE3 TRP A 161 3342 4444 6853 177 294 -1516 C ANISOU 99 CA GLY A 166 5253 5305 6091 922 -1145 -532 C

ATOM 55 CZ3 TRP A 161 22.153 -72.074 -63.924 1.00 32.78 C ATOM 100 C GLY A 166 15.796 -80.370 -59.423 1.00 58.76 C

ANISOU 55 CZ3 TRP A 161 2415 3651 6388 212 460 -1783 C ANISOU 100 C GLY A 166 7407 7099 7819 897 -1137 -396 C

ATOM 56 CH2 TRP A 161 22.696 -71.249 -64.926 1.00 48.47 C ATOM 101 O GLY A 166 15.092 -81.162 -58.791 1.00 62.85 O

ANISOU 56 CH2 TRP A 161 4352 5533 8531 36 788 -1884 C ANISOU 101 O GLY A 166 8120 7606 8155 948 -1257 -258 O

ATOM 57 CZ2 TRP A 161 21.928 -70.333 -65.593 1.0045.55 C ATOM 102 N TYR A 167 16.224 -80.621 -60.650 1.00 55.21 N

ANISOU 57 CZ2 TRP A 161 4152 5116 8039 -163 932 -1714 C ANISOU 102 N TYR A 167 6976 6568 7433 814 -982 -438 N

ATOM 58 C TRP A 161 16.763 -73.609 -62.669 1.00 34.15 C ATOM 103 CA TYR A 167 15.887 -81.878 -61.286 1.00 49.20 C

ANISOU 58 C TRP A 161 3517 4010 5448 163 -254 -725 C ANISOU 103 CA TYR A 167 6459 5708 6528 792 -973 -324 C

ATOM 59 O TRP A 161 17.583 -74.406 -62.219 1.00 36.07 O ATOM 104 CB TYR A 167 14.620 -81.744 -62.120 1.00 25.58 C

ANISOU 59 O TRP A 161 3682 4262 5762 324 -327 -858 O ANISOU 104 CB TYR A 167 3646 2676 3397 576 -881 -109 C

ATOM 60 N SER A 162 15.518 -73.543 -62.214 1.00 39.41 N ATOM 105 CG TYR A 167 14.215 -83.061 -62.711 1.00 35.84 C

ANISOU 60 N SERA 162 4305 4727 5941 128 -389 -532 N ANISOU 105 CG TYR A 167 5198 3870 4550 557 -890 6 C

ATOM 61 CA SER A 162 15.095 -74.397 -61.114 1.00 29.89 C ATOM 106 CD1 TYR A 167 13.920 -84.139 -61.874 1.0049.68 C

ANISOU 61 CA SER A 162 3153 3589 4613 271 -605 -465 C ANISOU 106 CD1 TYR A 167 7095 5606 6174 676 -1044 79 C

ATOM 62 C SER A 162 14.876 -75.814 -61.623 1.00 23.85 C ATOM 107 CE1 TYR A 167 13.564 -85.366 -62.379 1.00 46.91 C

ANISOU 62 C SER A 162 2623 2742 3696 288 -621 -366 C ANISOU 107 CE1 TYR A 167 6973 5152 5700 661 -1055 178 C

ATOM 63 O SER A 162 15.062 -76.783 -60.892 1.00 28.93 O ATOM 108 CZ TYR A 167 13.495 -85.541 -63.750 1.00 51.83 C

ANISOU 63 O SERA 162 3309 3402 4282 441 -761 -379 O ANISOU 108 CZ TYR A 167 7683 5690 6319 533 -920 203 C

ATOM 64 CB SER A 162 13.837 -73.867 -60.426 1.0040.44 C ATOM 109 OH TYR A 167 13.130 -86.773 -64.236 1.00 67.21 O

ANISOU 64 CB SER A 162 4532 5000 5833 220 -717 -307 C ANISOU 109 OH TYR A 167 9857 7533 8147 522 -941 297 O

ATOM 65 OG SER A 162 12.692 -74.127 -61.207 1.00 54.79 O ATOM 110 CE2 TYR A 167 13.790 -84.490 -64.620 1.00 44.14 C

ANISOU 65 OG SER A 162 6572 6752 7492 71 -685 -110 O ANISOU 110 CE2 TYR A 167 6591 4727 5454 417 -764 134 C

ATOM 66 N TYR A 163 14.484 -75.931 -62.886 1.00 23.57 N ATOM 111 CD2 TYR A 167 14.156 -83.253 -64.090 1.00 25.70 C

ANISOU 66 N TYR A 163 2759 2608 3590 134 -484 -269 N ANISOU 111 CD2 TYR A 167 4024 2492 3249 427 -744 37 C

ATOM 67 CA TYR A 163 14.335 -77.235 -63.506 1.00 28.48 C ATOM 112 C TYR A 167 16.995 -82.452 -62.152 1.0046.60 C

ANISOU 67 CA TYR A 163 3601 3140 4082 139 -483 -189 C ANISOU 112 C TYR A 167 6095 5295 6317 838 -872 -482 C

ATOM 68 CB TYR A 163 13.719 -77.119 -64.892 1.00 34.72 C ATOM 113 O TYR A 167 17.515 -83.537 -61.874 1.00 51.43 O

ANISOU 68 CB TYR A 163 4592 3821 4779 -44 -348 -71 C ANISOU 113 O TYR A 167 6770 5860 6910 995 -976 -543 O

ATOM 69 CG TYR A 163 13.306 -78.446 -65.478 1.00 37.27 C ATOM 114 N LEU A 168 17.346 -81.733 -63.211 1.00 43.65 N

ANISOU 69 CG TYR A 163 5162 4053 4945 -49 -378 39 C ANISOU 114 N LEU A 168 5634 4890 6060 701 -663 -551 N

ATOM 70 CD1 TYR A 163 12.506 -79.328 -64.749 1.00 39.18 C ATOM 115 CA LEU A 168 18.150 -82.314 -64.279 1.00 33.98 C

ANISOU 70 CD1 TYR A 163 5509 4321 5057 9 -548 163 C ANISOU 115 CA LEU A 168 4437 3565 4910 690 -513 -660 C

ATOM 71 CE1 TYR A 163 12.115 -80.546 -65.283 1.00 38.93 C ATOM 116 CB LEU A 168 18.264 -81.365 -65.470 1.00 30.00 C

ANISOU 71 CE1 TYR A 163 5701 4198 4894 0 -574 259 C ANISOU 116 CB LEU A 168 3900 3016 4483 497 -254 -687 C

ATOM 72 CZ TYR A 163 12.524 -80.891 -66.564 1.00 35.64 C ATOM 117 CG LEU A 168 17.030 -81.352 -66.369 1.00 36.41 C

ANISOU 72 CZ TYR A 163 5409 3669 4463 -61 -438 232 C ANISOU 117 CG LEU A 168 4980 3767 5086 307 -191 -450 C

ATOM 73 OH TYR A 163 12.129 -82.103 -67.081 1.0042.87 O ATOM 118 CD1 LEU A 168 17.256 -80.423 -67.544 1.00 31.34 C

ANISOU 73 OH TYR A 163 6546 4493 5251 -66 -474 322 O ANISOU 118 CD1 LEU A 168 4342 3059 4507 137 62 -491 C

ATOM 74 CE2 TYR A 163 13.322 -80.029 -67.308 1.00 32.75 C ATOM 119 CD2 LEU A 168 16.681 -82.770 -66.851 1.00 28.35 C

ANISOU 74 CE2 TYR A 163 4957 3275 4211 -120 -257 111 C ANISOU 119 CD2 LEU A 168 4213 2657 3903 329 -242 -346 C

ATOM 75 CD2 TYR A 163 13.707 -78.820 -66.762 1.00 37.16 C ATOM 120 C LEU A 168 19.526 -82.789 -63.834 1.00 44.16 C

ANISOU 75 CD2 TYR A 163 5288 3919 4911 -117 -223 16 C ANISOU 120 C LEU A 168 5539 4849 6390 895 -570 -916 C

ATOM 76 C TYR A 163 15.697 -77.905 -63.614 1.00 25.39 C ATOM 121 O LEU A 168 19.971 -83.868 -64.215 1.0045.07 O

ANISOU 76 C TYR A 163 3120 2712 3814 269 -435 -381 C ANISOU 121 O LEU A 168 5746 4885 6493 972 -575 -966 O

ATOM 77 O TYR A 163 15.836 -79.114 -63.453 1.00 36.60 O ATOM 122 N ARG A 169 20.125 -81.982 -62.989 1.00 46.34 N

ANISOU 77 O TYR A 163 4646 4099 5159 374 -522 -369 O ANISOU 122 N ARG A 169 5549 5204 6852 995 -628 -1092 N

ATOM 78 N TYR A 164 16.707 -77.098 -63.892 1.00 50.12 N ATOM 123 CA ARG A 169 21.377 -82.228 -62.347 1.00 62.71 C

ANISOU 78 N TYR A 164 6049 5843 7153 259 -291 -569 N ANISOU 123 CA ARG A 169 7419 7265 9143 1199 -701 -1369 C

ATOM 79 CA TYR A 164 18.058 -77.593 -64.022 1.00 28.03 C ATOM 124 CB ARG A 169 21.669 -81.068 -61.445 1.00 63.72 C

ANISOU 79 CA TYR A 164 3119 3007 4525 373 -226 -791 C ANISOU 124 CB ARG A 169 7208 7451 9553 1217 -635 -1604 C

ATOM 80 CB TYR A 164 18.911 -76.586 -64.779 1.00 29.02 C ATOM 125 CG ARG A 169 22.895 -80.329 -61.807 1.00 55.08 C

ANISOU 80 CB TYR A 164 3078 3087 4860 270 23 -960 C ANISOU 125 CG ARG A 169 6014 6468 8446 1314 -843 -1593 C

ATOM 81 CG TYR A 164 20.391 -76.807 -64.635 1.00 47.79 C ATOM 126 CD ARG A 169 22.684 -78.898 -61.490 1.00 55.94 C

ANISOU 81 CG TYR A 164 5214 5448 7495 401 81 -1248 C ANISOU 126 CD ARG A 169 5827 6620 8808 1243 -707 -1768 C

ATOM 82 CD1 TYR A 164 20.987 -77.963 -65.128 1.00 57.40 C ATOM 127 NE ARG A 169 22.761 -78.639 -60.078 1.00 70.61 N

ANISOU 82 CD1 TYR A 164 6504 6586 8719 472 118 -1323 C ANISOU 127 NE ARG A 169 7521 8579 10731 1388 -921 -1853 N

ATOM 83 CE1 TYR A 164 22.342 -78.174 -65.003 1.00 59.14 C ATOM 128 CZ ARG A 169 23.694 -77.870 -59.549 1.00 67.93 C

ANISOU 83 CE1 TYR A 164 6485 6786 9202 597 164 -1609 C ANISOU 128 CZ ARG A 169 6950 8281 10580 1357 -891 -2043 C ATOM 129 NH1 ARG A 169 24.611 -77.350 -60.327 1.00 60.38 N ATOM 174 CA LEU A 175 21.102 -91.830 -66.098 1.00 50.79 C

ANISOU 129 NH1 ARG A 169 5836 7266 9841 1251 -668 -2212 N ANISOU 174 CA LEU A 175 7452 5040 6807 1489 -892 -967 c

ATOM 130 NH2 ARG A 169 23.710 -77.624 -58.262 1.00 68.38 N ATOM 175 CB LEU A 175 20.475 -90.690 -66.885 1.00 49.50 c

ANISOU 130 NH2 ARG A 169 6991 8423 10568 1392 -1066 -2041 N ANISOU 175 CB LEU A 175 7266 4915 6626 1240 -666 -870 c

ATOM 131 C ARG A 169 21.331 -83.404 -61.453 1.00 65.45 C ATOM 176 CG LEU A 175 19.413 -91.054 -67.896 1.00 45.73 c

ANISOU 131 C ARG A 169 7861 7631 9376 1428 -1003 -1347 C ANISOU 176 CG LEU A 175 7081 4363 5931 1055 -579 -637 c

ATOM 132 O ARG A 169 22.301 -84.093 -61.318 1.00 73.90 O ATOM 177 CD1 LEU A 175 18.072 -91.160 -67.244 1.00 52.78 c

ANISOU 132 O ARG A 169 8813 8677 10587 1637 -1131 -1560 O ANISOU 177 CD1 LEU A 175 8141 5293 6620 1003 -736 -384 c

ATOM 133 N LEU A 170 20.244 -83.552 -60.735 1.00 64.80 N ATOM 178 CD2 LEU A 175 19.389 -90.058 -69.004 1.0040.45 c

ANISOU 133 N LEU A 170 8001 7580 9039 1391 -1117 -1095 N ANISOU 178 CD2 LEU A 175 6389 3679 5300 850 -315 -644 c

ATOM 134 CA LEU A 170 20.068 -84.719 -59.939 1.00 77.52 C ATOM 179 C LEU A 175 21.642 -92.863 -67.066 1.00 52.09 c

ANISOU 134 CA LEU A 170 9794 9175 10487 1577 -1364 -1028 C ANISOU 179 C LEU A 175 7728 5083 6983 1517 -814 -1041 c

ATOM 135 CB LEU A 170 18.816 -84.557 -59.104 1.00 77.11 C ATOM 180 O LEU A 175 21.090 -93.911 -67.175 1.00 57.07 o

ANISOU 135 CB LEU A 170 9910 9181 10207 1518 -1455 -787 C ANISOU 180 O LEU A 175 8622 5638 7426 1520 -900 -882 o

ATOM 136 CG LEU A 170 18.590 -83.230 -58.395 1.00 76.46 C ATOM 181 N GLN A 176 22.768 -92.609 -67.700 1.00 58.12 N

ANISOU 136 CG LEU A 170 9645 9214 10191 1503 -1485 -819 C ANISOU 181 N GLN A 176 8291 5820 7974 1529 -638 -1288 N

ATOM 137 CD1 LEU A 170 17.531 -83.409 -57.331 1.00 75.73 C ATOM 182 CA GLN A 176 23.321 -93.575 -68.645 1.00 50.45 c

ANISOU 137 CD1 LEU A 170 9757 9158 9859 1492 -1601 -600 C ANISOU 182 CA GLN A 176 7403 4731 7033 1553 -537 -1387 c

ATOM 138 CD2 LEU A 170 19.888 -82.769 -57.789 1.00 74.45 C ATOM 183 CB GLN A 176 24.651 -93.085 -69.228 1.00 60.10 c

ANISOU 138 CD2 LEU A 170 9141 8996 10150 1724 -1622 -1101 C ANISOU 183 CB GLN A 176 8340 5936 8557 1566 -318 -1701 c

ATOM 139 C LEU A 170 19.932 -85.961 -60.796 1.00 78.96 C ATOM 184 CG GLN A 176 24.683 -91.597 -69.528 1.00 72.92 c

ANISOU 139 C LEU A 170 10203 9243 10555 1571 -1335 -950 C ANISOU 184 CG GLN A 176 9788 7629 10290 1392 -93 -1736 c

ATOM 140 O LEU A 170 20.548 -86.963 -60.545 1.00 84.49 O ATOM 185 CD GLN A 176 25.022 -91.287 -70.975 1.00 79.12 c

ANISOU 140 O LEU A 170 10994 9886 11221 1765 -1503 -1011 O ANISOU 185 CD GLN A 176 10599 8332 11131 1209 265 -1809 c

ATOM 141 N FLE A 171 19.101 -85.893 -61.809 1.00 66.03 N ATOM 186 OE1 GLN A 176 24.610 -92.001 -71.889 1.00 83.90 o

ANISOU 141 N FLE A 171 8668 7563 8858 1354 -1129 -822 N ANISOU 186 OE1 GLN A 176 11467 8846 11566 1129 349 -1693 o

ATOM 142 CA FLE A 171 18.858 -87.025 -62.660 1.00 55.20 C ATOM 187 NE2 GLN A 176 25.785 -90.219 -71.189 1.00 85.31 N

ANISOU 142 CA ILE A 171 7555 6085 7332 1316 -1108 -695 C ANISOU 187 NE2 GLN A 176 11123 9138 12152 1142 486 -2007 N

ATOM 143 CB FLE A 171 17.487 -86.897 -63.326 1.00 61.34 C ATOM 188 C GLN A 176 23.531 -94.909 -67.946 1.00 52.03 c

ANISOU 143 CB FLE A 171 8543 6854 7908 1095 -1029 -421 C ANISOU 188 C GLN A 176 7714 4873 7182 1780 -802 -1407 c

ATOM 144 CGI ILE A 171 16.828 -88.256 -63.493 1.00 72.80 C ATOM 189 O GLN A 176 23.275 -95.977 -68.509 1.00 62.01 o

ANISOU 144 CGI FLE A 171 10208 8304 9150 1150 -1212 -234 C ANISOU 189 O GLN A 176 9205 6037 8319 1777 -809 -1325 o

ATOM 145 CD1 ILE A 171 15.944 -88.669 -62.340 1.00 59.38 C ATOM 190 N ALA A 177 23.982 -94.836 -66.699 1.00 52.81 N

ANISOU 145 CD1 FLE A 171 8790 6488 7285 1115 -1224 -89 C ANISOU 190 N ALA A 177 7671 5025 7371 1983 -1031 -1514 N

ATOM 146 CG2 ILE A 171 17.589 -86.242 -64.677 1.00 67.08 C ATOM 191 CA ALA A 177 24.251 -96.024 -65.895 1.00 46.56 c

ANISOU 146 CG2 FLE A 171 9421 7477 8591 959 -864 -368 C ANISOU 191 CA ALA A 177 6994 4168 6529 2229 -1312 -1548 c

ATOM 147 C FLE A 171 19.940 -87.480 -63.636 1.00 58.92 C ATOM 192 CB ALA A 177 24.894 -95.638 -64.578 1.0045.50 c

ANISOU 147 C FLE A 171 7971 6470 7945 1317 -956 -861 C ANISOU 192 CB ALA A 177 6662 4097 6530 2452 -1544 -1714 c

ATOM 148 O FLE A 171 20.138 -88.650 -63.801 1.00 54.29 O ATOM 193 C ALA A 177 22.987 -96.839 -65.644 1.00 51.22 c

ANISOU 148 O FLE A 171 7531 5797 7301 1409 -1017 -867 O ANISOU 193 C ALA A 177 7950 4711 6801 2180 -1434 -1233 c

ATOM 149 N LEU A 172 20.557 -86.515 -64.312 1.00 53.72 N ATOM 194 O ALA A 177 22.985 -98.066 -65.785 1.00 63.05 o

ANISOU 149 N LEU A 172 7108 5827 7477 1216 -749 -1004 N ANISOU 194 O ALA A 177 9651 6100 8206 2269 -1528 -1201 o

ATOM 150 CA LEU A 172 21.427 -86.756 -65.464 1.00 56.08 C ATOM 195 N ARG A 178 21.914 -96.159 -65.260 1.00 50.29 N

ANISOU 150 CA LEU A 172 7363 6036 7910 1184 -551 -1162 C ANISOU 195 N ARG A 178 7910 4670 6529 2039 -1429 -1012 N

ATOM 151 CB LEU A 172 21.790 -85.427 -66.135 1.00 35.51 C ATOM 196 CA ARG A 178 20.647 -96.825 -64.973 1.00 52.59 c

ANISOU 151 CB LEU A 172 4615 3435 5442 996 -269 -1235 C ANISOU 196 CA ARG A 178 8521 4917 6544 1971 -1521 -723 c

ATOM 152 CG LEU A 172 20.721 -84.809 -67.038 1.00 47.25 C ATOM 197 CB ARG A 178 19.618 -95.828 -64.440 1.00 59.25 c

ANISOU 152 CG LEU A 172 6311 4912 6729 762 -154 -983 C ANISOU 197 CB ARG A 178 9363 5863 7284 1827 -1505 -540 c

ATOM 153 CD1 LEU A 172 21.355 -83.886 -68.068 1.0045.09 C ATOM 198 CG ARG A 178 19.826 -95.466 -62.986 1.00 50.64 c

ANISOU 153 CD1 LEU A 172 5960 4596 6575 589 148 -1072 C ANISOU 198 CG ARG A 178 8195 4842 6203 2000 -1705 -586 c

ATOM 154 CD2 LEU A 172 19.899 -85.893 -67.718 1.00 52.67 C ATOM 199 CD ARG A 178 19.115 -94.178 -62.637 1.00 54.80 c

ANISOU 154 CD2 LEU A 172 7323 5514 7176 710 -190 -782 C ANISOU 199 CD ARG A 178 8617 5492 6711 1853 -1637 -485 c

ATOM 155 C LEU A 172 22.698 -87.558 -65.198 1.00 66.82 C ATOM 200 NE ARG A 178 17.667 -94.322 -62.492 1.00 51.78 N

ANISOU 155 C LEU A 172 8564 7354 9470 1409 -632 -1436 C ANISOU 200 NE ARG A 178 8469 5099 6104 1694 -1628 -203 N

ATOM 156 O LEU A 172 23.085 -88.395 -66.024 1.00 68.79 O ATOM 201 CZ ARG A 178 16.779 -93.470 -62.998 1.00 59.71 c

ANISOU 156 O LEU A 172 8895 7506 9735 1413 -536 -1497 O ANISOU 201 CZ ARG A 178 9446 6161 7080 1466 -1480 -73 c

ATOM 157 N PRO A 173 23.348 -87.342 -64.074 1.00 68.01 N ATOM 202 NH1 ARG A 178 17.194 -92.423 -63.697 1.00 59.37 N

ANISOU 157 N PRO A 173 8492 7571 9779 1601 -813 -1614 N ANISOU 202 NH1 ARG A 178 9182 6184 7193 1369 -1323 -182 N

ATOM 158 CA PRO A 173 24.640 -87.967 -63.826 1.00 56.26 C ATOM 203 NH2 ARG A 178 15.480 -93.665 -62.813 1.00 63.18 N

ANISOU 158 CA PRO A 173 6838 6030 8510 1820 -902 -1903 C ANISOU 203 ΝΉ2 ARG A 178 10080 6581 7343 1337 -1486 156 N

ATOM 159 CB PRO A 173 24.972 -87.501 -62.420 1.00 57.62 C ATOM 204 C ARG A 178 20.099 -97.524 -66.207 1.00 57.11 C

ANISOU 159 CB PRO A 173 6808 6284 8800 2021 -1150 -2046 C ANISOU 204 C ARG A 178 9298 5393 7008 1812 -1379 -600 c

ATOM 160 CG PRO A 173 24.282 -86.209 -62.270 1.00 62.84 C ATOM 205 O ARG A 178 19.438 -98.561 -66.123 1.00 60.12 o

ANISOU 160 CG PRO A 173 7395 7044 9437 1853 -1052 -1934 C ANISOU 205 O ARG A 178 9947 5684 7213 1820 -1475 -441 o

ATOM 161 CD PRO A 173 23.117 -86.184 -63.203 1.00 66.33 C ATOM 206 N FLE A 179 20.387 -96.936 -67.357 1.00 50.50 N

ANISOU 161 CD PRO A 173 8143 7471 9589 1631 -935 -1602 C ANISOU 206 N FLE A 179 8345 4566 6277 1669 -1146 -681 N

ATOM 162 C PRO A 173 24.563 -89.461 -63.819 1.00 48.33 C ATOM 207 CA FLE A 179 19.951 -97.456 -68.636 1.00 47.01 C

ANISOU 162 C PRO A 173 6079 4934 7351 1951 -1056 -1837 C ANISOU 207 CA ILE A 179 8090 4032 5740 1518 -996 -590 c

ATOM 163 O PRO A 173 25.404 -90.100 -64.359 1.00 55.00 O ATOM 208 CB FLE A 179 20.028 -96.343 -69.692 1.00 47.63 c

ANISOU 163 O PRO A 173 6867 5696 8336 2017 -988 -2017 O ANISOU 208 CB FLE A 179 8052 4149 5898 1325 -730 -636 c

ATOM 164 N GLU A 174 23.542 -90.003 -63.214 1.00 41.45 N ATOM 209 CGI ILE A 179 18.853 -95.376 -69.503 1.0042.06 c

ANISOU 164 N GLU A 174 5476 4071 6203 1982 -1247 -1588 N ANISOU 209 CGI FLE A 179 7383 3521 5076 1149 -715 -429 c

ATOM 165 CA GLU A 174 23.377 -91.446 -63.088 1.00 46.26 C ATOM 210 CD1 ILE A 179 18.911 -94.151 -70.393 1.00 36.23 c

ANISOU 165 CA GLU A 174 6341 4583 6652 2111 -1408 -1511 C ANISOU 210 CD1 FLE A 179 6541 2818 4407 973 -478 -468 c

ATOM 166 CB GLU A 174 22.772 -91.793 -61.725 1.0046.65 C ATOM 211 CG2 ILE A 179 20.079 -96.914 -71.097 1.00 39.24 c

ANISOU 166 CB GLU A 174 6545 4652 6528 2284 -1710 -1403 C ANISOU 211 CG2 FLE A 179 7147 2973 4790 1227 -560 -644 c

ATOM 167 CG GLU A 174 23.793 -91.922 -60.607 1.00 67.59 C ATOM 212 C FLE A 179 20.764 -98.693 -69.048 1.00 53.99 c

ANISOU 167 CG GLU A 174 9002 7342 9337 2520 -1924 -1649 C ANISOU 212 C FLE A 179 9041 4799 6674 1663 -1029 -731 c

ATOM 168 CD GLU A 174 24.975 -92.789 -60.994 1.00 91.29 C ATOM 213 O FLE A 179 20.220 -99.668 -69.578 1.00 53.06 o

ANISOU 168 CD GLU A 174 11961 10285 12441 2612 -1953 -1820 C ANISOU 213 O FLE A 179 9173 4579 6410 1620 -1044 -606 o

ATOM 169 OE1 GLU A 174 24.866 -94.028 -60.884 1.00 95.75 O ATOM 214 N ARG A 180 22.067 -98.649 -68.785 1.00 57.47 N

ANISOU 169 OE1 GLU A 174 12796 10769 12816 2682 -2074 -1704 O ANISOU 214 N ARG A 180 9248 5251 7336 1839 -1048 -1002

ATOM 170 OE2 GLU A 174 26.013 -92.231 -61.409 1.00 99.33 O ATOM 215 CA ARG A 180 22.937 -99.800 -69.000 1.00 67.50

ANISOU 170 OE2 GLU A 174 12676 11336 13730 2597 -1841 -2063 O ANISOU 215 CA ARG A 180 10546 6415 8687 2014 -1114 -1171

ATOM 171 C GLU A 174 22.550 -92.092 -64.201 1.00 50.45 C ATOM 216 CB ARG A 180 24.378 -99.465 -68.630 1.00 75.66

ANISOU 171 C GLU A 174 7157 5044 6967 1916 -1263 -1269 C ANISOU 216 CB ARG A 180 11251 7480 10018 2201 -1134 -1505

ATOM 172 O GLU A 174 22.392 -93.313 -64.221 1.00 43.46 O ATOM 217 CG ARG A 180 25.321 -99.335 -69.808 1.00 85.75

ANISOU 172 O GLU A 174 6525 4079 5910 1986 -1391 -1149 O ANISOU 217 CG ARG A 180 12363 8714 11502 2147 -868 -1739

ATOM 173 N LEU A 175 22.010 -91.290 -65.115 1.0048.09 N ATOM 218 CD ARG A 180 26.223 -98.120 -69.643 1.00102.62

ANISOU 173 N LEU A 175 6832 4764 6677 1677 -1006 -1201 N ANISOU 218 CD ARG A 180 14129 10940 13921 2153 -742 -1983 ATOM 219 NE ARG A 180 26.758 -98.000 -68.289 1.00115.10 N ATOM 264 CA HIS A 185 19.486-106.707 -66.448 1.00113.33 C

ANISOU 219 NE ARG A 180 15526 12580 15629 2381 -1012 -2116 N ANISOU 264 CA HIS A 185 13108 10222 19731 1250 299 -62 C

ATOM 220 CZ ARG A 180 27.389 -96.924 -67.824 1.00115.40 C ATOM 265 CB HIS A 185 19.352-105.927 -65.167 1.00119.64 C

ANISOU 220 CZ ARG A 180 15238 12734 15875 2376 -968 -2269 C ANISOU 265 CB HIS A 185 13998 11228 20233 1259 31 166 C

ATOM 221 NHl ARG A 180 27.567 -95.867 -68.604 1.00110.30 N ATOM 266 CG HIS A 185 20.518-106.076 -64.251 1.00127.12 C

ANISOU 221 NHl ARG A 180 14434 12099 15375 2215 -673 -2370 N ANISOU 266 CG HIS A 185 14970 11991 21338 1368 -268 422 C

ATOM 222 NH2 ARG A 180 27.841 -96.903 -66.575 1.00118.89 N ATOM 267 NDl HIS A 185 21.809-106.209 -64.711 1.00132.10 N

ANISOU 222 NH2 ARG A 180 15530 13278 16366 2520 -1218 -2316 N ANISOU 267 NDl HIS A 185 15466 12534 22191 1435 -308 413 N

ATOM 223 C ARG A 180 22.461-100.947 -68.134 1.00 65.71 C ATOM 268 CE1 HIS A 185 22.629-106.314 -63.682 1.00134.29 C

ANISOU 223 C ARG A 180 10565 6117 8286 2160 -1387 -1032 C ANISOU 268 CE1 HIS A 185 15827 12752 22443 1483 -594 633 C

ATOM 224 O ARG A 180 22.390-102.098 -68.575 1.00 63.24 O ATOM 269 NE2 HIS A 185 21.916-106.234 -62.571 1.00131.80 N

ANISOU 224 O ARG A 180 10454 5686 7889 2197 -1425 -996 O ANISOU 269 NE2 HIS A 185 15716 12492 21871 1451 -735 794 N

ATOM 225 N THR A 181 22.155-100.615 -66.885 1.00 66.20 N ATOM 270 CD2 HIS A 185 20.594-106.083 -62.900 1.00127.82 C

ANISOU 225 N THR A 181 10618 6244 8292 2244 -1570 -959 N ANISOU 270 CD2 HIS A 185 15234 12072 21259 1378 -537 676 C

ATOM 226 CA THR A 181 21.571-101.564 -65.960 1.00 74.70 C ATOM 271 0 TYR A 186 17.692-107.513 -70.296 1.00131.41 O

ANISOU 226 CA THR A 181 11946 7267 9168 2341 -1798 -793 C ANISOU 271 O TYR A 186 15518 12941 21472 828 1210 -1011 O

ATOM 227 CB THR A 181 21.175-100.898 -64.641 1.00 84.72 C ATOM 272 N TYR A 186 17.551-106.872 -67.930 1.00122.21 N

ANISOU 227 CB THR A 181 13172 8655 10364 2364 -1925 -708 C ANISOU 272 N TYR A 186 14368 11595 20470 974 689 -420 N

ATOM 228 OG1 THR A 181 22.351-100.429 -63.972 1.00 90.29 O ATOM 273 CA TYR A 186 16.276-107.410 -68.391 1.00126.62 C

ANISOU 228 OG1 THR A 181 13600 9441 11266 2542 -2025 -959 O ANISOU 273 CA TYR A 186 15060 12219 20832 789 818 -538 C

ATOM 229 CG2 THR A 181 20.442-101.889 -63.747 1.00 84.99 C ATOM 274 C TYR A 186 16.776-108.044 -69.692 1.00130.67 C

ANISOU 229 CG2 THR A 181 13445 8701 10146 2342 -2058 -523 C ANISOU 274 C TYR A 186 15514 12670 21466 773 1094 -857 C

ATOM 230 C THR A 181 20.337-102.168 -66.601 1.00 73.84 C ATOM 275 CB TYR A 186 15.179-106.337 -68.236 1.00124.50 C

ANISOU 230 C THR A 181 12126 7088 8842 2145 -1720 -531 C ANISOU 275 CB TYR A 186 14870 12344 20091 670 778 -522 C

ATOM 231 O THR A 181 20.229-103.378 -66.744 1.00 65.69 O ATOM 276 CG TYR A 186 15.431-105.545 -66.977 1.00119.70 C

ANISOU 231 O THR A 181 11256 5999 7704 2155 -1773 -478 O ANISOU 276 CG TYR A 186 14302 11897 19280 722 535 -265 C

ATOM 232 N TYR A 182 19.424-101.314 -67.037 1.00 74.70 N ATOM 277 CD2 TYR A 186 14.842-105.879 -65.786 1.00112.09 C

ANISOU 232 N TYR A 182 12245 7246 8890 1926 -1573 -379 N ANISOU 277 CD2 TYR A 186 13496 10964 18128 629 413 -66 C

ATOM 233 CA TYR A 182 18.179-101.800 -67.602 1.00 62.64 C ATOM 278 CD1 TYR A 186 16.328-104.509 -66.971 1.00122.36 C

ANISOU 233 CA TYR A 182 10959 5665 7175 1729 -1513 -142 C ANISOU 278 CD1 TYR A 186 14531 12369 19593 856 440 -233 C

ATOM 234 CB TYR A 182 17.217-100.669 -67.916 1.00 58.98 C ATOM 279 CE2 TYR A 186 15.110-105.182 -64.649 1.00109.74 C

ANISOU 234 CB TYR A 182 10461 5278 6672 1504 -1384 1 C ANISOU 279 CE2 TYR A 186 13261 10821 17613 687 197 153 C

ATOM 235 CG TYR A 182 15.879-101.195 -68.361 1.00 61.74 C ATOM 280 CE1 TYR A 186 16.594-103.809 -65.836 1.00118.54 C

ANISOU 235 CG TYR A 182 10951 5654 6853 1271 -1323 198 C ANISOU 280 CE1 TYR A 186 14097 12028 18915 908 205 -19 C

ATOM 236 CD1 TYR A 182 14.905-101.540 -67.428 1.00 58.52 C ATOM 281 CZ TYR A 186 15.987-104.147 -64.683 1.00113.64 C

ANISOU 236 CD1 TYR A 182 10537 5354 6343 1175 -1364 308 C ANISOU 281 CZ TYR A 186 13649 11436 18093 831 83 168 C

ATOM 237 CE1 TYR A 182 13.684-102.030 -67.827 1.00 59.84 C ATOM 282 0H TYR A 186 16.268-103.428 -63.556 1.00114.20 O

ANISOU 237 CE1 TYR A 182 10743 5557 6437 968 -1284 414 C ANISOU 282 OH TYR A 186 13791 11648 17951 899 -149 368 O

ATOM 238 CZ TYR A 182 13.431-102.193 -69.177 1.00 65.30 C ATOM 283 0 ASN A 187 15.356-110.153 -67.321 1.00112.92 O

ANISOU 238 CZ TYR A 182 11495 6197 7117 857 -1195 426 C ANISOU 283 O ASN A 187 13708 10078 19117 297 984 -574 O

ATOM 239 0H TYR A 182 12.217-102.683 -69.592 1.00 71.77 O ATOM 284 N ASN A 187 16.341-109.247 -70.046 1.00128.71 N

ANISOU 239 OH TYR A 182 12322 7054 7895 677 -1141 498 O ANISOU 284 N ASN A 187 15332 12168 21404 701 1202 -961 N

ATOM 240 CE2 TYR A 182 14.383-101.862 -70.124 1.00 65.98 C ATOM 285 CA ASN A 187 15.120-109.938 -69.671 1.00123.40 C

ANISOU 240 CE2 TYR A 182 11632 6183 7256 933 -1151 346 C ANISOU 285 CA ASN A 187 14790 11282 20816 601 1098 -798 C

ATOM 241 CD2 TYR A 182 15.599-101.380 -69.713 1.00 63.55 C ATOM 286 C ASN A 187 14.702-109.714 -68.258 1.00122.38 C

ANISOU 241 CD2 TYR A 182 11273 5815 7057 1137 -1198 224 C ANISOU 286 C ASN A 187 14790 11412 20299 410 1041 -714 C

ATOM 242 C TYR A 182 18.346-102.693 -68.831 1.00 65.69 C ATOM 287 CB ASN A 187 15.753-111.299 -69.623 1.00125.83 C

ANISOU 242 C TYR A 182 11475 5934 7552 1691 -1426 -173 C ANISOU 287 CB ASN A 187 15076 11274 21458 742 907 -544 C

ATOM 243 O TYR A 182 17.645-103.693 -68.987 1.00 65.11 O ATOM 288 CG ASN A 187 17.049-111.272 -68.863 1.00133.97 C

ANISOU 243 O TYR A 182 11555 5854 7331 1596 -1446 -44 O ANISOU 288 CG ASN A 187 16134 11892 22878 753 968 -594 C

ATOM 244 N ASN A 183 19.252-102.325 -69.722 1.00 68.48 N ATOM 289 OD1 ASN A 187 17.435-112.234 -68.206 1.00140.04 O

ANISOU 244 N ASN A 183 11672 6286 8060 1696 -1274 -366 N ANISOU 289 OD1 ASN A 187 16910 12592 23706 688 1172 -850 O

ATOM 245 CA ASN A 183 19.447-103.124 -70.921 1.00 66.45 C ATOM 290 ND2 ASN A 187 17.731-110.144 -68.937 1.00136.34 N

ANISOU 245 CA ASN A 183 11542 5917 7790 1659 -1172 -409 C ANISOU 290 ND2 ASN A 187 16464 11981 23356 826 765 -346 N

ATOM 246 CB ASN A 183 20.246-102.360 -71.970 1.00 49.23 C ATOM 291 0 ASN A 188 13.481-106.429 -69.712 1.00137.31 O

ANISOU 246 CB ASN A 183 9175 3769 5763 1587 -927 -595 C ANISOU 291 O ASN A 188 16554 13697 21921 422 1393 -1280 O

ATOM 247 CG ASN A 183 19.437-101.253 -72.611 1.00 55.28 C ATOM 292 N ASN A 188 13.542-109.092 -68.123 1.00130.97 N

ANISOU 247 CG ASN A 183 9949 4595 6460 1347 -757 -466 C ANISOU 292 N ASN A 188 15845 12870 21047 393 1051 -778 N

ATOM 248 OD1 ASN A 183 18.205-101.284 -72.589 1.00 53.34 O ATOM 293 CA ASN A 188 12.752-108.698 -69.297 1.00132.44 C

ANISOU 248 OD1 ASN A 183 9882 4339 6046 1219 -814 -239 O ANISOU 293 CA ASN A 188 16081 13338 20901 223 1149 -944 C

ATOM 249 ND2 ASN A 183 20.121-100.265 -73.183 1.00 54.63 N ATOM 294 C ASN A 188 13.358-107.566 -70.145 1.00130.85 C

ANISOU 249 ND2 ASN A 183 9675 4566 6518 1286 -548 -619 N ANISOU 294 C ASN A 188 15824 13056 20835 261 1346 -1247 C

ATOM 250 C ASN A 183 20.063-104.485 -70.629 1.00 75.19 C ATOM 295 CB ASN A 188 11.295-108.364 -68.869 1.00130.18 C

ANISOU 250 C ASN A 183 12745 6918 8906 1864 -1329 -498 C ANISOU 295 CB ASN A 188 15771 13455 20238 234 1072 -907 C

ATOM 251 O ASN A 183 19.620-105.500 -71.166 1.00 78.02 O ATOM 296 CG ASN A 188 11.072-106.888 -68.574 1.00 87.73 C

ANISOU 251 O ASN A 183 13281 7220 9143 1798 -1332 -399 O ANISOU 296 CG ASN A 188 10286 8220 14829 358 1154 -1080 C

ATOM 252 N GLN A 184 21.133-104.524 -69.856 1.00 80.73 N ATOM 297 OD1 ASN A 188 10.563-106.151 -69.415 1.00 95.34 O

ANISOU 252 N GLN A 184 13264 7663 9747 2075 -1454 -680 N ANISOU 297 OD1 ASN A 188 11236 9184 15804 337 1333 -1343 O

ATOM 253 CA GLN A 184 21.670-105.801 -69.444 1.00 91.89 C ATOM 298 ND2 ASN A 188 11.425-106.457 -67.362 1.00 66.22 N

ANISOU 253 CA GLN A 184 14695 9048 11170 2244 -1610 -767 C ANISOU 298 ND2 ASN A 188 7498 5624 12036 482 1017 -927 N

ATOM 254 CB GLN A 184 23.058-105.634 -68.847 1.00100.74 C ATOM 299 0 LEU A 189 15.291-108.371 -73.265 1.00110.59 O

ANISOU 254 CB GLN A 184 15525 10227 12525 2453 -1686 -1048 C ANISOU 299 O LEU A 189 13161 10540 18319 411 1754 -1836 O

ATOM 255 CG GLN A 184 24.053-104.976 -69.772 1.00107.62 C ATOM 300 N LEU A 189 13.651-107.852 -71.399 1.00124.07 N

ANISOU 255 CG GLN A 184 16153 11093 13644 2446 -1471 -1306 C ANISOU 300 N LEU A 189 15016 12363 19764 123 1457 -1472 N

ATOM 256 CD GLN A 184 25.196-104.357 -69.015 1.00112.72 C ATOM 301 CA LEU A 189 13.405-109.124 -72.033 1.00121.52 C

ANISOU 256 CD GLN A 184 16451 11843 14536 2597 -1536 -1557 C ANISOU 301 CA LEU A 189 14716 11891 19564 97 1639 -1767 C

ATOM 257 OE1 GLN A 184 25.187-104.318 -67.791 1.00116.08 O ATOM 302 C LEU A 189 14.470-109.263 -73.079 1.00113.32 C

ANISOU 257 OE1 GLN A 184 16843 12341 14921 2712 -1759 -1525 O ANISOU 302 C LEU A 189 13596 10729 18730 285 1770 -1896 C

ATOM 258 NE2 GLN A 184 26.187-103.873 -69.734 1.00112.69 N ATOM 303 CB LEU A 189 12.016-109.176 -72.676 1.00125.08 C

ANISOU 258 NE2 GLN A 184 16185 11851 14781 2581 -1328 -1808 N ANISOU 303 CB LEU A 189 15228 12615 19680 -58 1696 -1989 C

ATOM 259 C GLN A 184 20.809-106.581 -68.473 1.00 94.56 C ATOM 304 CG LEU A 189 10.756-108.647 -71.964 1.00127.32 C

ANISOU 259 C GLN A 184 15215 9417 11295 2246 -1797 -568 C ANISOU 304 CG LEU A 189 15519 13229 19627 -170 1562 -1847 C

ATOM 260 O GLN A 184 20.570-107.743 -68.667 1.00 97.43 O ATOM 305 CD1 LEU A 189 9.742-108.113 -72.961 1.00126.49 C

ANISOU 260 O GLN A 184 15759 9723 11537 2222 -1839 -487 O ANISOU 305 CD1 LEU A 189 15458 13351 19252 -307 1616 -2103 C

ATOM 261 N HIS A 185 20.265-105.961 -67.445 1.00108.20 N ATOM 306 CD2 LEU A 189 10.083-109.681 -71.086 1.00 74.54 C

ANISOU 261 N HIS A 185 12282 9713 19115 1301 496 -276 N ANISOU 306 CD2 LEU A 189 8872 6457 12993 -279 1447 -1584 C

ATOM 262 C HIS A 185 18.122-107.285 -66.815 1.00116.07 C ATOM 307 N LEU A 190 14.457-110.396 -73.749 1.00104.26 N

ANISOU 262 C HIS A 185 13619 10627 19856 1058 449 -161 C ANISOU 307 N LEU A 190 12479 9290 17846 303 1909 -2077 N

ATOM 263 O HIS A 185 17.560-108.043 -66.050 1.00113.01 O ATOM 308 CA LEU A 190 15.388-110.668 -74.798 1.00 68.03 C

ANISOU 263 O HIS A 185 13385 10120 19433 984 344 -2 O ANISOU 308 CA LEU A 190 7820 4558 13472 476 2083 -2233 C ATOM 309 CB LEU A 190 15.224-112.066 -75.325 1.00 86.22 C ATOM 354 NE2 GLN A 196 22.296 -96.893 -73.801 1.00104.02 N

ANISOU 309 CB LEU A 190 10187 6536 16036 468 2203 -2408 C ANISOU 354 NE2 GLN A 196 11193 11060 17271 1350 1394 -1034 N

ATOM 310 CG LEU A 190 15.519-113.176 -74.350 1.00 72.84 C ATOM 355 C GLN A 196 20.494 -92.059 -73.388 1.00 60.44 C

ANISOU 310 CG LEU A 190 8517 4533 14627 422 2063 -2213 c ANISOU 355 C GLN A 196 5796 6486 10684 1322 913 -906 C

ATOM 311 CD2 LEU A 190 16.779-112.852 -73.600 1.00 74.17 c ATOM 356 O GLN A 196 21.037 -91.690 -72.347 1.00 61.96 O

ANISOU 311 CD2 LEU A 190 8557 4616 15010 579 1925 -1920 c ANISOU 356 O GLN A 196 5894 6601 11045 1395 651 -707 O

ATOM 312 CD1 LEU A 190 15.676-114.429 -75.158 1.00 76.01 c ATOM 357 N ARG A 197 19.650 -91.294 -74.050 1.00 54.71 N

ANISOU 312 CD1 LEU A 190 8985 4720 15174 394 2140 -2358 c ANISOU 357 N ARG A 197 5209 6035 9543 1244 958 -1022 N

ATOM 313 C LEU A 190 15.166-109.722 -75.900 1.00 75.09 c ATOM 358 CA ARG A 197 19.252 -89.991 -73.570 1.00 52.91 C

ANISOU 313 C LEU A 190 8729 5745 14058 489 2221 -2447 c ANISOU 358 CA ARG A 197 5011 6031 9060 1248 720 -919 C

ATOM 314 O LEU A 190 16.008-109.613 -76.735 1.00 73.82 o ATOM 359 CB ARG A 197 19.297 -88.979 -74.686 1.00 52.63 C

ANISOU 314 O LEU A 190 8528 5572 13950 604 2379 -2565 o ANISOU 359 CB ARG A 197 5008 6164 8827 1225 887 -1034 C

ATOM 315 N ARG A 191 14.021-109.063 -75.948 1.00 82.50 N ATOM 360 CG ARG A 197 20.442 -89.155 -75.621 1.00 48.63 C

ANISOU 315 N ARG A 191 9731 7004 14610 353 2136 -2457 N ANISOU 360 CG ARG A 197 4354 5479 8644 1280 1160 -1068 C

ATOM 316 CA ARG A 191 13.870-107.966 -76.905 1.00 78.40 c ATOM 361 CD ARG A 197 20.454 -88.029 -76.617 1.00 68.47 C

ANISOU 316 CA ARG A 191 9251 6783 13757 351 2228 -2643 c ANISOU 361 CD ARG A 197 6930 8178 10908 1253 1288 -1143 C

ATOM 317 CB ARG A 191 12.721-108.193 -77.851 1.00 73.01 c ATOM 362 NE ARG A 197 21.664 -88.006 -77.426 1.00 82.41 N

ANISOU 317 CB ARG A 191 8716 6199 12826 177 2242 -2875 c ANISOU 362 NE ARG A 197 8614 9810 12890 1267 1533 -1128 N

ATOM 318 CG ARG A 191 12.137-109.591 -77.842 1.00 84.33 c ATOM 363 CZ ARG A 197 22.350 -86.910 -77.707 1.00 88.41 C

ANISOU 318 CG ARG A 191 10222 7343 14476 65 2237 -2946 c ANISOU 363 CZ ARG A 197 9287 10592 13713 1286 1513 -1013 C

ATOM 319 CD ARG A 191 13.170-110.689 -77.957 1.00 96.27 c ATOM 364 NH1 ARG A 197 23.428 -86.984 -78.443 1.00 80.56 N

ANISOU 319 CD ARG A 191 11747 8494 16336 185 2409 -3086 c ANISOU 364 NH1 ARG A 197 8238 9479 12891 1273 1741 -995 N

ATOM 320 NE ARG A 191 12.594-111.811 -78.648 1.00104.48 N ATOM 365 NH2 ARG A 197 21.958 -85.735 -77.255 1.00 92.14 N

ANISOU 320 NE ARG A 191 12917 9383 17398 66 2434 -3284 N ANISOU 365 ΝΉ2 ARG A 197 9724 11202 14084 1314 1259 -921 N

ATOM 321 CZ ARG A 191 11.832-112.709 -78.068 1.00112.51 c ATOM 366 C ARG A 197 17.893 -89.926 -72.906 1.00 52.07 C

ANISOU 321 CZ ARG A 191 13968 10191 18592 -76 2342 -3244 c ANISOU 366 C ARG A 197 5072 6134 8577 1177 517 -911 C

ATOM 322 NH1 ARG A 191 11.598-112.635 -76.778 1.00112.22 N ATOM 367 O ARG A 197 17.079 -90.807 -73.038 1.00 46.29 O

ANISOU 322 NH1 ARG A 191 13852 10166 18620 -125 2184 -2931 N ANISOU 367 O ARG A 197 4447 5418 7722 1096 601 -1018 O

ATOM 323 NH2 ARG A 191 11.336-113.695 -78.774 1.00123.75 N ATOM 368 N LEU A 198 17.678 -88.822 -72.200 1.00 36.02 N

ANISOU 323 ΝΉ2 ARG A 191 15503 11492 20022 -177 2355 -3432 N ANISOU 368 N LEU A 198 3057 4257 6373 1208 255 -785 N

ATOM 324 C ARG A 191 13.791-106.573 -76.267 1.00 77.81 C ATOM 369 CA LEU A 198 16.403 -88.550 -71.578 1.00 37.30 C

ANISOU 324 C ARG A 191 9103 7025 13435 371 2081 -2443 c ANISOU 369 CA LEU A 198 3370 4656 6146 1152 83 -788 C

ATOM 325 O ARG A 191 12.924-106.312 -75.466 1.00 76.08 o ATOM 370 CB LEU A 198 16.594 -87.940 -70.191 1.00 38.99 C

ANISOU 325 O ARG A 191 8909 6977 13022 256 1915 -2317 o ANISOU 370 CB LEU A 198 3579 4903 6334 1231 -251 -582 C

ATOM 326 N GLY A 192 14.718-105.704 -76.652 1.00 59.28 N ATOM 371 CG LEU A 198 15.318 -87.612 -69.413 1.00 39.89 C

ANISOU 326 N GLY A 192 6666 4746 11113 519 2151 -2418 N ANISOU 371 CG LEU A 198 3827 5128 6199 1203 -428 -517 C

ATOM 327 CA GLY A 192 14.932-104.394 -76.064 1.00 83.82 C ATOM 372 CD1 LEU A 198 15.654 -87.013 -68.056 1.00 33.43 C

ANISOU 327 CA GLY A 192 9701 8121 14024 558 2011 -2236 c ANISOU 372 CD1 LEU A 198 3062 4481 5159 1267 -714 -405 C

ATOM 328 C GLY A 192 14.800-103.329 -77.113 1.00 75.54 c ATOM 373 CD2 LEU A 198 14.427 -86.673 -70.212 1.00 32.49 C

ANISOU 328 C GLY A 192 8697 7330 12675 570 2128 -2415 c ANISOU 373 CD2 LEU A 198 3000 4357 4987 1079 -267 -692 C

ATOM 329 O GLY A 192 13.950-103.488 -77.952 1.00 68.42 o ATOM 374 C LEU A 198 15.754 -87.549 -72.515 1.00 35.15 C

ANISOU 329 O GLY A 192 7930 6516 11549 470 2204 -2642 o ANISOU 374 C LEU A 198 3186 4640 5529 1095 167 -945 C

ATOM 330 N ALA A 193 15.641-102.290 -77.141 1.00 69.65 N ATOM 375 O LEU A 198 16.266 -86.450 -72.727 1.0044.16 O

ANISOU 330 N ALA A 193 7852 6696 11917 684 2134 -2320 N ANISOU 375 O LEU A 198 4289 5851 6640 1137 129 -917 O

ATOM 331 CA ALA A 193 16.566-101.835 -76.107 1.00 61.52 c ATOM 376 N TYR A 199 14.625 -87.948 -73.079 1.00 42.52 N

ANISOU 331 CA ALA A 193 6658 5588 11127 798 1997 -2050 c ANISOU 376 N TYR A 199 4239 5703 6213 997 269 -1108 N

ATOM 332 CB ALA A 193 17.937-102.384 -76.357 1.00 60.58 c ATOM 377 CA TYR A 199 13.914 -87.150 -74.025 1.00 48.62 C

ANISOU 332 CB ALA A 193 6411 5173 11432 944 2166 -2065 c ANISOU 377 CA TYR A 199 5113 6714 6646 946 313 -1261 C

ATOM 333 C ALA A 193 16.625-100.303 -76.117 1.00 63.09 c ATOM 378 CB TYR A 199 13.350 -88.023 -75.116 1.00 43.25 C

ANISOU 333 C ALA A 193 6822 6084 11065 827 1914 -1975 c ANISOU 378 CB TYR A 199 4519 6028 5887 854 558 -1488 C

ATOM 334 O ALA A 193 16.621 -99.703 -77.150 1.00 59.63 o ATOM 379 CG TYR A 199 14.409 -88.469 -76.040 1.00 43.73 C

ANISOU 334 O ALA A 193 6439 5799 10417 825 2063 -2141 o ANISOU 379 CG TYR A 199 4523 5886 6208 887 819 -1549 C

ATOM 335 N VAL A 194 16.703 -99.697 -74.949 1.00 50.17 N ATOM 380 CD1 TYR A 199 15.221 -89.522 -75.723 1.00 51.53 C

ANISOU 335 N VAL A 194 5113 4518 9432 859 1672 -1727 N ANISOU 380 CD1 TYR A 199 5403 6600 7576 925 913 -1484 C

ATOM 336 CA VAL A 194 16.514 -98.258 -74.765 1.00 55.43 c ATOM 381 CE1 TYR A 199 16.208 -89.931 -76.567 1.00 49.04 C

ANISOU 336 CA VAL A 194 5783 5489 9791 857 1542 -1658 c ANISOU 381 CE1 TYR A 199 5019 6095 7520 968 1168 -1545 C

ATOM 337 CB VAL A 194 16.109 -97.925 -73.316 1.00 61.87 c ATOM 382 CZ TYR A 199 16.398 -89.274 -77.726 1.0048.01 C

ANISOU 337 CB VAL A 194 6604 6400 10505 837 1244 -1419 c ANISOU 382 CZ TYR A 199 4945 6049 7248 968 1349 -1660 C

ATOM 338 CGI VAL A 194 15.228 -99.007 -72.759 1.00 58.98 c ATOM 383 OH TYR A 199 17.376 -89.659 -78.573 1.00 57.63 O

ANISOU 338 CGI VAL A 194 6323 5921 10166 738 1197 -1395 c ANISOU 383 OH TYR A 199 6100 7079 8718 1015 1637 -1721 O

ATOM 339 CG2 VAL A 194 17.313 -97.777 -72.426 1.00 67.41 c ATOM 384 CE2 TYR A 199 15.604 -88.221 -78.064 1.00 51.17 C

ANISOU 339 CG2 VAL A 194 7166 6950 11499 973 1097 -1193 c ANISOU 384 CE2 TYR A 199 5472 6714 7256 926 1248 -1714 C

ATOM 340 C VAL A 194 17.624 -97.312 -75.219 1.00 57.36 ATOM 385 CD2 TYR A 199 14.625 -87.818 -77.215 1.0046.97 C

ANISOU 340 C VAL A 194 5898 5743 10153 979 1615 -1623 ANISOU 385 CD2 TYR A 199 4989 6366 6489 890 976 -1661 C

ATOM 341 O VAL A 194 18.776 -97.606 -75.061 1.00 60.20 ATOM 386 C TYR A 199 12.858 -86.362 -73.294 1.0046.31 C

ANISOU 341 O VAL A 194 6114 5859 10900 1089 1689 -1562 ANISOU 386 C TYR A 199 4899 6667 6030 933 69 -1222 C

ATOM 342 N SERA 195 17.254 -96.152 -75.728 1.00 47.46 ATOM 387 O TYR A 199 12.030 -86.881 -72.623 1.00 37.25 O

ANISOU 342 N SER A 195 4689 4763 8581 959 1594 -1660 ANISOU 387 O TYR A 199 3797 5571 4785 884 4 -1220 O

ATOM 343 CA SER A 195 18.226 -95.156 -76.114 1.00 51.50 ATOM 388 N FLE A 200 12.963 -85.066 -73.425 1.00 46.68 N

ANISOU 343 CA SER A 195 5087 5304 9176 1055 1658 -1613 ANISOU 388 N FLE A 200 4954 6854 5928 983 -59 -1182 N

ATOM 344 CB SER A 195 17.607 -94.112 -77.000 1.00 57.14 ATOM 389 CA FLE A 200 12.113 -84.154 -72.701 1.00 45.80 C

ANISOU 344 CB SER A 195 5918 6307 9484 1002 1713 -1738 ANISOU 389 CA ILE A 200 4906 6963 5533 1000 -305 -1134 C

ATOM 345 OG SER A 195 17.317 -94.673 -78.245 1.00 67.53 ATOM 390 CB FLE A 200 12.931 -83.100 -71.989 1.00 34.87 C

ANISOU 345 OG SER A 195 7372 7623 10664 948 1964 -1991 ANISOU 390 CB FLE A 200 3465 5556 4228 1107 -523 -954 C

ATOM 346 C SER A 195 18.886 -94.536 -74.905 1.0049.50 c ATOM 391 CGI ILE A 200 13.804 -83.775 -70.937 1.00 32.54 C

ANISOU 346 C SER A 195 4692 5018 9099 1137 1392 -1348 c ANISOU 391 CGI FLE A 200 3080 5025 4257 1168 -599 -777 C

ATOM 347 O SERA 195 18.451 -94.742 -73.810 1.00 50.41 o ATOM 392 CD1 ILE A 200 14.642 -82.817 -70.148 1.00 29.05 C

ANISOU 347 O SER A 195 4842 5148 9163 1115 1150 -1209 o ANISOU 392 CD1 FLE A 200 2581 4530 3924 1276 -850 -598 C

ATOM 348 N GLN A 196 19.997 -93.851 -75.108 1.00 59.41 N ATOM 393 CG2 ILE A 200 12.015 -82.071 -71.347 1.00 37.87 C

ANISOU 348 N GLN A 196 5796 6223 10556 1231 1436 -1277 ANISOU 393 CG2 FLE A 200 3931 6174 4284 1136 -769 -931 C

ATOM 349 CA GLN A 196 20.854 -93.405 -74.008 1.00 64.26 ATOM 394 C FLE A 200 11.143 -83.497 -73.653 1.00 41.34 C

ANISOU 349 CA GLN A 196 6247 6731 11438 1327 1187 -1037 ANISOU 394 C FLE A 200 4446 6631 4630 945 -279 -1310 C

ATOM 350 CB GLN A 196 22.314 -93.372 -74.452 1.00 55.36 ATOM 395 O FLE A 200 11.538 -82.887 -74.641 1.00 63.22 O

ANISOU 350 CB GLN A 196 4998 5459 10577 1350 1287 -961 ANISOU 395 O FLE A 200 7239 9424 7357 951 -195 -1374 O

ATOM 351 CG GLN A 196 22.888 -94.734 -74.727 1.00 76.79 ATOM 396 N LEU A 201 9.865 -83.649 -73.358 1.00 33.16 N

ANISOU 351 CG GLN A 196 7686 7928 13564 1346 1450 -1011 ANISOU 396 N LEU A 201 3474 5762 3365 890 -349 -1387 N

ATOM 352 CD GLN A 196 22.736 -95.666 -73.538 1.00 97.02 ATOM 397 CA LEU A 201 8.831 -83.119 -74.214 1.00 36.22 C

ANISOU 352 CD GLN A 196 10235 10306 16323 1377 1248 -905 ANISOU 397 CA LEU A 201 3949 6318 3495 820 -346 -1513 C

ATOM 353 OE1 GLN A 196 22.997 -95.283 -72.396 1.00 99.29 ATOM 398 CB LEU A 201 7.568 -83.962 -74.105 1.00 34.09 C

ANISOU 353 OE1 GLN A 196 10473 10568 16686 1419 952 -707 ANISOU 398 CB LEU A 201 3699 6049 3203 701 -302 -1545 C ATOM 399 CG LEU A 201 7.658 -85.302 -74.816 1.00 40.99 C ATOM 444 O GLY A 207 0.657 -81.093 -72.829 1.00 45.28 O

ANISOU 399 CG LEU A 201 4586 6836 4154 636 -90 -1747 C ANISOU 444 O GLY A 207 3769 5310 8126 876 -155 858 o

ATOM 400 CD1 LEU A 201 6.421 -86.121 -74.500 1.00 51.18 C ATOM 445 N VAL A 208 -0.102 -80.773 -70.735 1.00 55.32 N

ANISOU 400 CD1 LEU A 201 5876 8155 5413 528 -88 -1788 C ANISOU 445 N VAL A 208 4658 6534 9826 778 586 1257 N

ATOM 401 CD2 LEU A 201 7.783 -85.059 -76.308 1.00 47.57 C ATOM 446 CA VAL A 208 0.537 -81.952 -70.178 1.0049.52 C

ANISOU 401 CD2 LEU A 201 5509 7584 4982 571 20 -1780 C ANISOU 446 CA VAL A 208 3873 5774 9167 755 1021 1502 c

ATOM 402 C LEU A 201 8.542 -81.681 -73.829 1.00 37.07 C ATOM 447 CB VAL A 208 1.398 -81.585 -68.971 1.00 49.49 c

ANISOU 402 C LEU A 201 4076 6421 3588 840 -490 -1294 C ANISOU 447 CB VAL A 208 4054 6105 8644 737 1511 1954 c

ATOM 403 O LEU A 201 8.344 -81.363 -72.650 1.00 29.14 O ATOM 448 CGI VAL A 208 2.171 -82.810 -68.476 1.00 42.72 c

ANISOU 403 O LEU A 201 3074 5387 2610 877 -585 -1154 O ANISOU 448 CGI VAL A 208 3207 5240 7785 751 1915 2194 c

ATOM 404 N LEU A 202 8.519 -80.814 -74.829 1.00 34.29 N ATOM 449 CG2 VAL A 208 2.335 -80.438 -69.336 1.00 42.90 c

ANISOU 404 N LEU A 202 3777 6031 3221 801 -452 -1264 N ANISOU 449 CG2 VAL A 208 3657 5713 6932 763 1279 2016 c

ATOM 405 CA LEU A 202 8.213 -79.416 -74.603 1.00 40.08 C ATOM 450 C VAL A 208 -0.520 -82.949 -69.732 1.00 54.82 c

ANISOU 405 CA LEU A 202 4561 6690 3978 799 -512 -1097 C ANISOU 450 C VAL A 208 4076 5998 10757 703 1276 1420 c

ATOM 406 CB LEU A 202 9.460 -78.569 -74.788 1.00 31.05 C ATOM 451 O VAL A 208 -1.303 -82.656 -68.829 1.00 67.74 o

ANISOU 406 CB LEU A 202 3404 5543 2851 885 -554 -1071 C ANISOU 451 O VAL A 208 5460 7512 12765 648 1566 1509 o

ATOM 407 CG LEU A 202 10.540 -78.866 -73.762 1.00 36.65 C ATOM 452 N PRO A 209 -0.544 -84.129 -70.319 1.00 59.87 N

ANISOU 407 CG LEU A 202 4042 6260 3623 1002 -656 -1052 C ANISOU 452 N PRO A 209 4596 6384 11767 712 1180 1239 N

ATOM 408 CD1 LEU A 202 11.919 -78.657 -74.376 1.0046.89 C ATOM 453 CA PRO A 209 -1.500 -85.151 -69.928 1.00 66.95 c

ANISOU 408 CD1 LEU A 202 5252 7623 4942 1104 -701 -1123 C ANISOU 453 CA PRO A 209 5044 6826 13567 644 1412 1120 c

ATOM 409 CD2 LEU A 202 10.344 -77.972 -72.554 1.00 30.81 C ATOM 454 CB PRO A 209 -1.468 -86.114 -71.088 1.00 56.90 c

ANISOU 409 CD2 LEU A 202 3393 5357 2958 962 -723 -853 C ANISOU 454 CB PRO A 209 3736 5339 12546 681 1063 810 c

ATOM 410 C LEU A 202 7.102 -78.924 -75.515 1.00 44.85 C ATOM 455 CG PRO A 209 -1.048 -85.296 -72.218 1.00 79.05 c

ANISOU 410 C LEU A 202 5251 7236 4556 688 -470 -1073 C ANISOU 455 CG PRO A 209 6956 8469 14609 775 565 708 c

ATOM 411 O LEU A 202 7.366 -78.236 -76.506 1.00 36.94 O ATOM 456 CD PRO A 209 -0.012 -84.401 -71.645 1.00 69.42 c

ANISOU 411 O LEU A 202 4292 6224 3518 681 -454 -1083 O ANISOU 456 CD PRO A 209 6065 7689 12622 779 820 1092 c

ATOM 412 N PRO A 203 5.855 -79.310 -75.198 1.00 45.03 N ATOM 457 C PRO A 209 -1.161 -85.876 -68.658 1.00 67.95 c

ANISOU 412 N PRO A 203 5238 7305 4567 663 -469 -1097 N ANISOU 457 C PRO A 209 5304 6905 13610 560 2004 1478 c

ATOM 413 CA PRO A 203 4.694 -78.745 -75.887 1.00 39.17 C ATOM 458 O PRO A 209 -0.031 -85.933 -68.258 1.00 70.33 o

ANISOU 413 CA PRO A 203 4470 6630 3783 662 -474 -1140 C ANISOU 458 O PRO A 209 5919 7494 13307 611 2209 1785 o

ATOM 414 CB PRO A 203 3.507 -79.484 -75.261 1.00 34.94 C ATOM 459 N ASP A 210 -2.184 -86.426 -68.032 1.00 77.10 N

ANISOU 414 CB PRO A 203 3880 6149 3246 629 -469 -1175 C ANISOU 459 N ASP A 210 6319 7680 15296 451 2202 1397 N

ATOM 415 CG PRO A 203 4.016 -79.980 -73.920 1.00 41.04 C ATOM 460 CA ASP A 210 -2.050 -87.226 -66.834 1.00 85.13 c

ANISOU 415 CG PRO A 203 4651 6889 4055 648 -479 -1108 C ANISOU 460 CA ASP A 210 7534 8542 16270 429 2646 1652 c

ATOM 416 CD PRO A 203 5.465 -80.327 -74.210 1.00 42.10 C ATOM 461 CB ASP A 210 -3.451 -87.651 -66.364 1.00 95.97 c

ANISOU 416 CD PRO A 203 4851 6935 4211 633 -467 -1096 C ANISOU 461 CB ASP A 210 8669 9456 18340 333 2782 1469 c

ATOM 417 C PRO A 203 4.575 -77.263 -75.576 1.00 33.03 C ATOM 462 CG ASP A 210 -3.567 -87.738 -64.853 1.00 99.87 c

ANISOU 417 C PRO A 203 3663 5871 3017 762 -521 -1078 C ANISOU 462 CG ASP A 210 9401 9895 18649 369 3146 1710 c

ATOM 418 O PRO A 203 4.496 -76.884 -74.404 1.00 29.27 O ATOM 463 OD2 ASP A 210 -3.522 -88.871 -64.318 1.00102.43 o

ANISOU 418 O PRO A 203 3157 5392 2572 827 -542 -1023 O ANISOU 463 OD2 ASP A 210 9807 10003 19107 409 3427 1813 o

ATOM 419 N LEU A 204 4.550 -76.439 -76.616 1.00 34.53 N ATOM 464 OD1 ASP A 210 -3.703 -86.678 -64.203 1.00 84.79 o

ANISOU 419 N LEU A 204 4868 5402 2849 967 -1660 593 N ANISOU 464 OD1 ASP A 210 7590 8161 16466 379 3121 1772 o

ATOM 420 CA LEU A 204 4.412 -75.002 -76.445 1.00 44.90 C ATOM 465 C ASP A 210 -1.241 -88.438 -67.193 1.00 86.00 C

ANISOU 420 CA LEU A 204 6331 6766 3965 763 -1569 611 C ANISOU 465 C ASP A 210 7701 8602 16374 475 2746 1727 C

ATOM 421 CB LEU A 204 4.730 -74.268 -77.743 1.00 39.38 C ATOM 466 O ASP A 210 -0.401 -88.882 -66.447 1.00 82.91 O

ANISOU 421 CB LEU A 204 5789 6036 3137 554 -1615 386 C ANISOU 466 O ASP A 210 7620 8312 15570 551 3002 2000 O

ATOM 422 CG LEU A 204 6.178 -74.408 -78.192 1.00 41.48 C ATOM 467 N ASN A 211 -1.562 -88.957 -68.361 1.00 87.26 N

ANISOU 422 CG LEU A 204 6112 6441 3209 287 -1336 442 C ANISOU 467 N ASN A 211 7565 8604 16985 463 2467 1429 N

ATOM 423 CD1 LEU A 204 6.389 -73.632 -79.468 1.00 37.62 C ATOM 468 CA ASN A 211 -1.023 -90.153 -68.900 1.00 73.27 C

ANISOU 423 CD1 LEU A 204 5844 5843 2607 375 -1443 197 C ANISOU 468 CA ASN A 211 5763 6706 15370 502 2516 1416 C

ATOM 424 CD2 LEU A 204 7.122 -73.920 -77.101 1.00 30.08 C ATOM 469 CB ASN A 211 -2.201 -91.082 -69.108 1.00 83.13 C

ANISOU 424 CD2 LEU A 204 4768 4979 1683 105 -1007 597 C ANISOU 469 CB ASN A 211 6699 7425 17461 390 2541 1133 C

ATOM 425 C LEU A 204 3.026 -74.601 -75.932 1.00 53.13 C ATOM 470 CG ASN A 211 -1.810 -92.473 -69.497 1.00106.96 C

ANISOU 425 C LEU A 204 7149 7660 5379 993 -1806 552 C ANISOU 470 CG ASN A 211 9721 10237 20681 408 2735 1185 C

ATOM 426 O LEU A 204 2.873 -73.560 -75.297 1.00 58.32 O ATOM 471 OD1 ASN A 211 -1.291 -92.708 -70.580 1.00110.81 O

ANISOU 426 O LEU A 204 7870 8434 5857 914 -1652 687 O ANISOU 471 OD1 ASN A 211 10025 10618 21460 446 2429 911 (

ATOM 427 N ASP A 205 2.013 -75.416 -76.210 1.00 50.93 N ATOM 472 ND2 ASN A 211 -2.125 -93.420 -68.646 1.00119.38 N

ANISOU 427 N ASP A 205 6480 7001 5869 1062 -1977 313 N ANISOU 472 ND2 ASN A 211 11544 11741 22072 427 3195 1509

ATOM 428 CA ASP A 205 0.672 -75.116 -75.716 1.00 55.17 C ATOM 473 C ASN A 211 -0.435 -89.819 -70.238 1.00 73.45 C

ANISOU 428 CA ASP A 205 6646 7285 7031 1099 -2013 207 C ANISOU 473 C ASN A 211 5743 6969 15196 645 2056 1231 C

ATOM 429 CB ASP A 205 -0.422 -75.845 -76.516 1.00 52.86 C ATOM 474 O ASN A 211 -1.135 -89.445 -71.143 1.00 85.46 O

ANISOU 429 CB ASP A 205 6034 6567 7484 1199 -2403 -206 C ANISOU 474 O ASN A 211 7141 8397 16934 647 1566 860 O

ATOM 430 CG ASP A 205 -0.287 -77.370 -76.471 1.00 62.05 C ATOM 475 N LEU A 212 0.854 -90.013 -70.380 1.00 67.52 N

ANISOU 430 CG ASP A 205 6881 7556 9138 1164 -2186 -191 C ANISOU 475 N LEU A 212 5355 6528 13770 734 2081 1443 N

ATOM 431 OD2 ASP A 205 -0.667 -78.010 -77.476 1.00 75.31 O ATOM 476 CA LEU A 212 1.511 -89.867 -71.655 1.00 68.19 C

ANISOU 431 OD2 ASP A 205 8489 8979 11146 1244 -2568 -529 O ANISOU 476 CA LEU A 212 5692 6818 13400 815 1542 1226 C

ATOM 432 OD1 ASP A 205 0.197 -77.923 -75.453 1.0045.81 O ATOM 477 CB LEU A 212 3.009 -89.882 -71.446 1.00 63.81 C

ANISOU 432 OD1 ASP A 205 4669 5611 7126 1067 -1649 149 O ANISOU 477 CB LEU A 212 5547 6700 11999 900 1668 1525 C

ATOM 433 C ASP A 205 0.566 -75.434 -74.215 1.00 57.84 C ATOM 478 CG LEU A 212 3.920 -89.921 -72.654 1.00 67.58 C

ANISOU 433 C ASP A 205 6622 7668 7688 1005 -1407 556 C ANISOU 478 CG LEU A 212 6323 7406 11950 982 1223 1355 C

ATOM 434 O ASP A 205 -0.477 -75.211 -73.589 1.00 57.84 O ATOM 479 CD1 LEU A 212 3.256 -89.250 -73.828 1.00 75.08 C

ANISOU 434 O ASP A 205 6284 7487 8205 1009 -1322 525 O ANISOU 479 CD1 LEU A 212 7292 8342 12894 980 629 983 C

ATOM 435 N CYS A 206 1.647 -75.980 -73.662 1.00 42.18 N ATOM 480 CD2 LEU A 212 5.229 -89.251 -72.287 1.00 47.46 C

ANISOU 435 N CYS A 206 4715 5916 5396 931 -992 871 N ANISOU 480 CD2 LEU A 212 4146 5360 8525 1039 1382 1655 C

ATOM 436 CA CYS A 206 1.754 -76.299 -72.237 1.00 45.96 C ATOM 481 C LEU A 212 1.114 -90.933 -72.641 1.00 79.56 C

ANISOU 436 CA CYS A 206 4940 6470 6052 858 -397 1236 C ANISOU 481 C LEU A 212 6953 7887 15389 819 1309 908 C

ATOM 437 CB CYS A 206 1.669 -75.033 -71.378 1.00 43.88 C ATOM 482 O LEU A 212 0.964 -90.683 -73.807 1.00 80.85 O

ANISOU 437 CB CYS A 206 4782 6426 5465 825 -225 1444 C ANISOU 482 O LEU A 212 7131 8009 15580 855 767 554 O

ATOM 438 SG CYS A 206 3.051 -73.897 -71.628 1.00 51.52 S ATOM 483 N SERA 213 0.991 -92.149 -72.159 1.00 86.18 N

ANISOU 438 SG CYS A 206 6362 7888 5326 788 -285 1600 S ANISOU 483 N SER A 213 7639 8443 16661 786 1725 1033 N

ATOM 439 C CYS A 206 0.723 -77.325 -71.778 1.00 53.16 C ATOM 484 CA SER A 213 0.613 -93.255 -73.004 1.00 96.17 C

ANISOU 439 C CYS A 206 5323 6993 7884 854 -206 1170 C ANISOU 484 CA SER A 213 8738 9341 18461 780 1578 766 C

ATOM 440 O CYS A 206 0.384 -77.396 -70.595 1.00 51.86 O ATOM 485 CB SER A 213 0.726 -94.540 -72.224 1.00 97.60 C

ANISOU 440 O CYS A 206 4904 6796 8005 804 236 1406 O ANISOU 485 CB SER A 213 8778 9212 19093 727 2166 983 C

ATOM 441 N GLY A 207 0.219 -78.108 -72.725 1.00 57.04 N ATOM 486 OG SER A 213 0.238 -95.598 -73.001 1.00 96.24 O

ANISOU 441 N GLY A 207 5657 7181 8835 902 -536 837 N ANISOU 486 OG SER A 213 8738 9239 18591 728 2676 1408 O

ATOM 442 CA GLY A 207 -0.716 -79.171 -72.422 1.00 45.53 C ATOM 487 C SER A 213 -0.785 -93.166 -73.593 1.00105.94 C

ANISOU 442 CA GLY A 207 3704 5334 8262 883 -372 730 C ANISOU 487 C SER A 213 9639 10262 20350 727 1151 299 C

ATOM 443 C GLY A 207 0.010 -80.436 -72.013 1.00 45.38 C ATOM 488 O SERA 213 -0.983 -93.458 -74.760 1.00111.89 O

ANISOU 443 C GLY A 207 3619 5306 8315 842 31 955 C ANISOU 488 O SER A 213 10365 10864 21283 768 739 -24 O ATOM 489 N MET A 214 -1.748 -92.797 -72.759 1.00103.52 N ATOM 534 CA ARG A 220 3.020 -97.081 -75.372 1.00 60.48 (

ANISOU 489 N MET A 214 9076 9859 20399 646 1236 247 N ANISOU 534 CA ARG A 220 5708 8192 9078 -908 1133 -133 ATOM 490 CA MET A 214 -3.137 -92.766 -73.175 1.00107.12 C ATOM 535 CB ARG A 220 2.793 -98.388 -76.118 1.00 65.47 ( ANISOU 490 CA MET A 214 9241 10089 21369 628 764 -218 C ANISOU 535 CB ARG A 220 6374 8710 9791 -1252 1048 -229 ATOM 491 CB MET A 214 -4.041 -92.384 -72.002 1.00112.52 C ATOM 536 CG ARG A 220 2.451 -99.550 -75.230 1.00 81.76 ( ANISOU 491 CB MET A 214 9590 10354 22808 416 1024 -361 C ANISOU 536 CG ARG A 220 8513 10642 11912 -1608 1130 -137 ATOM 492 CG MET A 214 -5.212 -93.329 -71.788 1.00119.93 C ATOM 537 CD ARG A 220 2.623-100.853 -75.977 1.00 92.84 ANISOU 492 CG MET A 214 10266 10958 24342 370 549 -897 C ANISOU 537 CD ARG A 220 10080 11777 13417 -1910 1047 -246 ATOM 493 SD MET A 214 -6.666 -92.865 -72.748 1.00179.49 S ATOM 538 NE ARG A 220 1.405-101.301 -76.631 1.00104.97 ANISOU 493 SD MET A 214 17963 18728 31506 561 -300 -1277 S ANISOU 538 NE ARG A 220 11345 13587 14950 -2224 994 -357 ATOM 494 CE MET A 214 -6.734 -94.209 -73.930 1.00 80.71 C ATOM 539 CZ ARG A 220 0.412-101.905 -75.990 1.00108.81 ANISOU 494 CE MET A 214 5281 5856 19531 542 -695 -1742 C ANISOU 539 CZ ARG A 220 11665 14209 15470 -2570 1095 -290

ATOM 495 C MET A 214 -3.290 -91.764 -74.303 1.00112.71 C ATOM 540 NH1 ARG A 220 -0.673-102.298 -76.645 1.00108.87

ANISOU 495 C MET A 214 10105 11106 21612 686 399 -283 C ANISOU 540 NH1 ARG A 220 11384 14481 15499 -2875 1022 -416

ATOM 496 O MET A 214 -4.050 -91.981 -75.246 1.00115.31 O ATOM 541 ΝΉ2 ARG A 220 0.508-102.109 -74.683 1.00111.49 N

ANISOU 496 O MET A 214 10493 11641 21677 655 682 -10 O ANISOU 541 ΝΉ2 ARG A 220 12124 14423 15815 -2611 1271 98 N

ATOM 497 N ALA A 215 -2.567 -90.656 -74.192 1.00117.16 N ATOM 542 C ARG A 220 3.998 -97.283 -74.227 1.00 64.38 C

ANISOU 497 N ALA A 215 10732 11662 22120 774 -236 -667 N ANISOU 542 C ARG A 220 6483 8363 9614 -860 1184 -22 C ATOM 498 CA ALA A 215 -2.729 -89.573 -75.116 1.00118.83 C ATOM 543 O ARG A 220 5.192 -97.494 -74.448 1.00 69.74 o ANISOU 498 CA ALA A 215 11145 12109 21896 861 -733 -836 C ANISOU 543 O ARG A 220 7400 8711 10387 -767 1117 -53 o ATOM 499 CB ALA A 215 -1.915 -88.381 -74.673 1.00114.08 C ATOM 544 N PHE A 221 3.494 -97.200 -73.002 1.00 68.57 N ANISOU 499 CB ALA A 215 10838 11922 20585 857 -497 -454 C ANISOU 544 N PHE A 221 6979 9009 10066 -900 1304 109 N

ATOM 500 C ALA A 215 -2.407 -89.940 -76.555 1.00116.17 C ATOM 545 CA PHE A 221 4.340 -97.367 -71.836 1.00 61.90 C

ANISOU 500 C ALA A 215 11128 11872 21141 976 -1228 -1030 C ANISOU 545 CA PHE A 221 6408 7898 9214 -834 1333 218 c

ATOM 501 O ALA A 215 -3.025 -89.413 -77.456 1.00116.67 O ATOM 546 CB PHE A 221 3.572 -97.065 -70.555 1.00 51.11 c

ANISOU 501 O ALA A 215 11388 12041 20902 1073 -1759 -1279 O ANISOU 546 CB PHE A 221 4981 6740 7699 -834 1490 356 c

ATOM 502 N ASP A 216 -1.403 -90.778 -76.793 1.00102.02 N ATOM 547 CG PHE A 221 4.291 -97.479 -69.311 1.00 53.73 c

ANISOU 502 N ASP A 216 9410 10043 19309 971 -1032 -903 N ANISOU 547 CG PHE A 221 5621 6812 7982 -811 1512 479 c ATOM 503 CA ASP A 216 -0.988 -91.053 -78.164 1.00 81.17 C ATOM 548 CD1 PHE A 221 5.260 -96.656 -68.751 1.00 50.85 c ANISOU 503 CA ASP A 216 6993 7411 16438 1070 -1460 -1122 C ANISOU 548 CD1 PHE A 221 5425 6327 7567 -516 1440 471 c ATOM 504 CB ASP A 216 0.430 -90.546 -78.449 1.00 68.17 C ATOM 549 CE1 PHE A 221 5.933 -97.033 -67.600 1.00 47.34 c ANISOU 504 CB ASP A 216 5853 6219 13831 1127 -1437 -842 C ANISOU 549 CE1 PHE A 221 5264 5670 7052 -473 1420 575 c ATOM 505 CG ASP A 216 0.872 -90.780 -79.881 1.00 75.45 C ATOM 550 CZ PHE A 221 5.637 -98.259 -66.996 1.0049.71 c ANISOU 505 CG ASP A 216 7062 7194 14411 1238 -1976 -1116 C ANISOU 550 CZ PHE A 221 5714 5851 7323 -709 1505 716 c ATOM 506 OD1 ASP A 216 0.801 -91.903 -80.361 1.00 87.85 O ATOM 551 CE2 PHE A 221 4.670 -99.094 -67.552 1.00 51.54 c ANISOU 506 OD1 ASP A 216 8516 8516 16347 1264 -2073 -1291 O ANISOU 551 CE2 PHE A 221 5792 6166 7625 -1029 1612 732 c ATOM 507 OD2 ASP A 216 1.311 -89.857 -80.550 1.00 70.57 O ATOM 552 CD2 PHE A 221 4.007 -98.700 -68.701 1.00 60.21 c ANISOU 507 OD2 ASP A 216 6802 6860 13153 1298 -2290 -1156 O ANISOU 552 CD2 PHE A 221 6575 7499 8801 -1087 1599 602 c

ATOM 508 C ASP A 216 -1.106 -92.517 -78.408 1.00 85.47 C ATOM 553 C PHE A 221 4.877 -98.786 -71.799 1.00 66.05 c

ANISOU 508 C ASP A 216 7279 7605 17592 1028 -1259 -1186 C ANISOU 553 C PHE A 221 7175 8073 9846 -1074 1294 245 c

ATOM 509 O ASP A 216 -0.919 -93.307 -77.500 1.00 94.35 O ATOM 554 O PHE A 221 4.125 -99.755 -71.951 1.00 69.47 o

ANISOU 509 O ASP A 216 8316 8685 18848 950 -696 -869 O ANISOU 554 O PHE A 221 7557 8526 10310 -1395 1343 257 o

ATOM 510 N PRO A 217 -1.499 -92.866 -79.704 1.00 83.09 N ATOM 555 N LEU A 222 6.182 -98.915 -71.604 1.00 57.16 N

ANISOU 510 N PRO A 217 6865 7037 17668 1086 -1712 -1600 N ANISOU 555 N LEU A 222 6308 6620 8788 -921 1209 252 N ATOM 511 CA PRO A 217 -1.630 -94.312 -79.897 1.00 81.29 C ATOM 556 CA LEU A 222 6.797-100.226 -71.524 1.00 58.48 c ANISOU 511 CA PRO A 217 6412 6473 18003 1042 -1521 -1664 C ANISOU 556 CA LEU A 222 6739 6428 9051 -1080 1177 293 c ATOM 512 CB PRO A 217 -2.714 -94.438 -80.978 1.00 89.92 C ATOM 557 CB LEU A 222 8.097-100.261 -72.318 1.00 68.01 c ANISOU 512 CB PRO A 217 7250 7246 19670 1029 -2027 -2197 C ANISOU 557 CB LEU A 222 8082 7360 10400 -902 1052 196 c ATOM 513 CG PRO A 217 -2.869 -93.094 -81.605 1.00 92.23 C ATOM 558 CG LEU A 222 8.011-100.741 -73.758 1.00 67.43 c ANISOU 513 CG PRO A 217 7702 7726 19616 1114 -2532 -2410 C ANISOU 558 CG LEU A 222 7975 7227 10420 -1017 1013 50 c ATOM 514 CD PRO A 217 -1.785 -92.233 -81.080 1.00 85.60 C ATOM 559 CD2 LEU A 222 7.111-101.961 -73.861 1.00 61.70 c ANISOU 514 CD PRO A 217 7242 7313 17967 1197 -2395 -2034 C ANISOU 559 CD2 LEU A 222 7286 6462 9693 -1394 1066 57 c

ATOM 515 C PRO A 217 -0.343 -94.984 -80.347 1.00 72.50 C ATOM 560 CD1 LEU A 222 9.409-101.051 -74.244 1.00 60.29 c

ANISOU 515 C PRO A 217 5664 5552 16332 1119 -1524 -1504 C ANISOU 560 CD1 LEU A 222 7274 5978 9655 -845 938 4 c

ATOM 516 O PRO A 217 -0.236 -96.180 -80.307 1.00 74.21 O ATOM 561 C LEU A 222 7.092-100.595 -70.088 1.00 56.21 c

ANISOU 516 O PRO A 217 5775 5545 16878 1095 -1312 -1480 O ANISOU 561 C LEU A 222 6675 6000 8680 -1060 1226 466 c ATOM 517 N ASN A 218 0.628 -94.196 -80.761 1.00 84.13 N ATOM 562 O LEU A 222 6.644-101.627 -69.587 1.00 54.92 o

ANISOU 517 N ASN A 218 7567 7436 16963 1208 -1755 -1405 N ANISOU 562 O LEU A 222 6641 5730 8495 -1301 1321 576 o ATOM 518 CA ASN A 218 1.910 -94.711 -81.164 1.00 80.88 C ATOM 563 N ASP A 223 7.851 -99.740 -69.422 1.00 55.33 N ANISOU 518 CA ASN A 218 7510 7257 15966 1281 -1748 -1256 C ANISOU 563 N ASP A 223 6627 5882 8514 -772 1160 487 N ATOM 519 CB ASN A 218 2.374 -94.042 -82.429 1.00 65.84 C ATOM 564 CA ASP A 223 8.398-100.110 -68.138 1.00 55.70 c ANISOU 519 CB ASN A 218 5956 5557 13503 1396 -2337 -1498 C ANISOU 564 CA ASP A 223 6935 5759 8469 -695 1147 631 c ATOM 520 CG ASN A 218 1.551 -94.437 -83.607 1.00 69.10 C ATOM 565 CB ASP A 223 9.437-101.219 -68.336 1.00 63.37 c ANISOU 520 CG ASN A 218 6205 5617 14433 1460 -2869 -1984 C ANISOU 565 CB ASP A 223 8159 6343 9575 -702 1050 656 c ATOM 521 OD1 ASN A 218 1.218 -95.581 -83.755 1.00 71.77 O ATOM 566 CG ASP A 223 9.612-102.085 -67.108 1.00 79.65 c ANISOU 521 OD1 ASN A 218 6308 5633 15328 1451 -2833 -2121 O ANISOU 566 CG ASP A 223 10524 8218 11521 -722 1083 848 c ATOM 522 ND2 ASN A 218 1.216 -93.493 -84.444 1.00 69.06 N ATOM 567 OD1 ASP A 223 8.656-102.172 -66.305 1.00 92.81 o ANISOU 522 ND2 ASN A 218 6335 5661 14242 1536 -3375 -2258 N ANISOU 567 OD1 ASP A 223 12208 10034 13023 -854 1239 970 o

ATOM 523 C ASN A 218 2.938 -94.558 -80.076 1.00 76.59 C ATOM 568 OD2 ASP A 223 10.703-102.673 -66.952 1.00 79.79 o

ANISOU 523 C ASN A 218 7193 7078 14829 1259 -1240 -771 C ANISOU 568 OD2 ASP A 223 10763 7945 11608 -587 964 888 o

ATOM 524 O ASN A 218 4.107 -94.714 -80.319 1.00 72.42 O ATOM 569 C ASP A 223 9.042 -98.920 -67.452 1.00 58.61 c

ANISOU 524 O ASN A 218 6993 6838 13685 1326 -1238 -633 O ANISOU 569 C ASP A 223 7311 6205 8753 -391 1055 606 c

ATOM 525 N FLE A 219 2.496 -94.208 -78.881 1.00 66.32 N ATOM 570 O ASP A 223 9.082 -97.813 -67.990 1.00 57.58 o

ANISOU 525 N FLE A 219 6081 9555 9561 -94 952 -404 N ANISOU 570 O ASP A 223 6994 6227 8655 -251 1026 483 o ATOM 526 CA FLE A 219 3.393 -94.166 -77.738 1.00 65.72 C ATOM 571 N LYS A 224 9.553 -99.165 -66.255 1.00 56.49 N

ANISOU 526 CA ILE A 219 6212 9181 9579 -72 1048 -310 C ANISOU 571 N LYS A 224 7283 5817 8366 -289 1006 721 N

ATOM 527 CB FLE A 219 3.620 -92.745 -77.206 1.00 64.88 C ATOM 572 CA LYS A 224 10.285 -98.164 -65.513 1.00 57.81 c

ANISOU 527 CB FLE A 219 6116 9124 9411 274 1156 -241 C ANISOU 572 CA LYS A 224 7501 6018 8447 -20 876 680 c ATOM 528 CGI ILE A 219 4.273 -91.873 -78.271 1.00 59.25 C ATOM 573 CB LYS A 224 9.728 -98.051 -64.105 1.00 52.80 c ANISOU 528 CGI FLE A 219 5506 8318 8690 570 1152 -300 C ANISOU 573 CB LYS A 224 7028 5506 7528 17 964 813 c ATOM 529 CD1 ILE A 219 4.549 -90.458 -77.806 1.00 57.36 C ATOM 574 CG LYS A 224 8.361 -97.472 -64.055 1.00 60.84 c ANISOU 529 CD1 FLE A 219 5316 8071 8409 892 1271 -246 C ANISOU 574 CG LYS A 224 7864 6837 8417 -68 1183 828 c ATOM 530 CG2 ILE A 219 4.496 -92.778 -75.962 1.00 57.46 C ATOM 575 CD LYS A 224 8.252 -96.576 -62.852 1.00 72.80 c ANISOU 530 CG2 FLE A 219 5381 7903 8550 264 1212 -167 C ANISOU 575 CD LYS A 224 9494 8494 9670 134 1203 850 c

ATOM 531 C FLE A 219 2.808 -95.035 -76.641 1.00 58.39 C ATOM 576 CE LYS A 224 6.871 -96.013 -62.766 1.00 80.98 c

ANISOU 531 C FLE A 219 5219 8293 8675 -380 1094 -229 C ANISOU 576 CE LYS A 224 10342 9852 10575 83 1452 88800 C

ATOM 532 0 FLE A 219 1.721 -94.769 -76.135 1.00 64.43 O ATOM 577 NZ LYS A 224 5.905 -96.904 -63.482 1.00 86.45 N

ANISOU 532 O FLE A 219 5734 9391 9357 -415 1164 -170 O ANISOU 577 NZ LYS A 224 10843 10620 11384 -217 1618 949 N ATOM 533 N ARG A 220 3.532 -96.084 -76.286 1.00 54.92 N ATOM 578 C LYS A 224 11.758 -98.513 -65.435 1.00 62.08 C

ANISOU 533 N ARG A 220 5009 7508 8349 -588 1075 -216 N ANISOU 578 C LYS A 224 8190 6281 9115 136 658 659 C ATOM 579 O LYS A 224 12.138 -99.685 -65452 1.00 64.62 O ATOM 624 CB FLE A 230 18.179 -87.538 -53.982 1.00105.04 C

ANISOU 579 O LYS A 224 8681 6373 9501 73 633 750 O ANISOU 624 CB FLE A 230 15193 12122 12595 1958 -1845 -1041 C

ATOM 580 N LEU A 225 12.586 -97.481 -65.349 1.00 61.28 N ATOM 625 CGI ILE A 230 17.152 -88.005 -55.010 1.00104.55 C

ANISOU 580 N LEU A 225 8020 6200 9064 343 506 537 N ANISOU 625 CGI FLE A 230 14959 12086 12678 1863 -1408 -819 C

ATOM 581 CA LEU A 225 14.001 -97.653 -65.072 1.00 60.96 C ATOM 626 CG2 ILE A 230 18.903 -86.301 -54.458 1.00105.54 C

ANISOU 581 CA LEU A 225 8073 5954 9135 514 276 512 C ANISOU 626 CG2 FLE A 230 15063 12070 12969 1856 -1977 -1352 C

ATOM 582 CB LEU A 225 14.741 -96.349 -65.340 1.00 63.08 C ATOM 627 CD1 ILE A 230 17.745 -88.229 -56.383 1.00104.69 C

ANISOU 582 CB LEU A 225 8165 6271 9529 664 156 332 C ANISOU 627 CD1 FLE A 230 14579 11987 13209 1717 -1392 -826 C

ATOM 583 CG LEU A 225 15.092 -96.002 -66.780 1.00 63.22 C ATOM 628 N ASP A 231 21.086 -87.838 -52.482 1.00115.91 N

ANISOU 583 CG LEU A 225 7960 6235 9824 646 202 206 C ANISOU 628 N ASP A 231 16583 13462 13997 2110 -2974 -1372 N

ATOM 584 CD1 LEU A 225 15.547 -94.564 -66.830 1.00 62.08 C ATOM 629 CA ASP A 231 21.641 -87.140 -51.355 1.00120.15 C

ANISOU 584 CD1 LEU A 225 7679 6160 9749 766 146 51 C ANISOU 629 CA ASP A 231 17336 14052 14261 2219 -3418 -1602 C

ATOM 585 CD2 LEU A 225 16.190 -96.920 -67.288 1.00 58.08 C ATOM 630 CB ASP A 231 22.261 -88.073 -50.356 1.00123.58 C

ANISOU 585 CD2 LEU A 225 7327 5338 9403 688 99 219 C ANISOU 630 CB ASP A 231 17760 14547 14647 2373 -3831 -1503 C

ATOM 586 C LEU A 225 14.151 -98.022 -63.605 1.00 74.14 C ATOM 631 CG ASP A 231 21.380 -88.242 -49.187 1.00128.77 C

ANISOU 586 C LEU A 225 10011 7601 10559 610 182 645 C ANISOU 631 CG ASP A 231 18883 15309 14735 2606 -3803 -1258 C

ATOM 587 O LEU A 225 13.228 -97.771 -62.813 1.00 81.92 O ATOM 632 OD1 ASP A 231 20.737 -89.295 -49.084 1.00126.27 O

ANISOU 587 O LEU A 225 11087 8754 11286 575 306 718 O ANISOU 632 OD1 ASP A 231 18942 15052 13982 2675 -3670 -1305 O

ATOM 588 N PRO A 226 15.306 -98.602 -63.227 1.00 72.48 N ATOM 633 OD2 ASP A 231 21.278 -87.276 -48.411 1.00134.04 O

ANISOU 588 N PRO A 226 9932 7198 10411 757 -29 682 N ANISOU 633 OD2 ASP A 231 19559 15984 15387 2731 -3885 -1010 O

ATOM 589 CA PRO A 226 15.532 -98.814 -61.798 1.00 72.91 C ATOM 634 C ASP A 231 22.444 -85.889 -51.637 1.00125.72 C

ANISOU 589 CA PRO A 226 10256 7253 10193 901 -159 796 C ANISOU 634 C ASP A 231 17842 14665 15262 2056 -3605 -1975 C

ATOM 590 CB PRO A 226 16.926 -99.447 -61.745 1.00 64.66 C ATOM 635 O ASP A 231 23.430 -85.578 -50.971 1.00130.82 O

ANISOU 590 CB PRO A 226 9267 5999 9301 1083 -415 811 C ANISOU 635 O ASP A 231 18489 15333 15883 2074 -4069 -2215 O

ATOM 591 CG PRO A 226 17.583 -99.030 -63.029 1.00 61.65 C ATOM 636 N ARG A 232 21.995 -85.170 -52.642 1.00126.23 N

ANISOU 591 CG PRO A 226 8577 5565 9282 1069 -446 640 C ANISOU 636 N ARG A 232 17735 14620 15606 1893 -3243 -2024 N

ATOM 592 CD PRO A 226 16.464 -99.019 -64.032 1.00 62.04 C ATOM 637 CA ARG A 232 22.454 -83.831 -52.862 1.00134.44 C

ANISOU 592 CD PRO A 226 8513 5672 9386 835 -162 623 C ANISOU 637 CA ARG A 232 18668 15529 16885 1731 -3322 -2364 C

ATOM 593 C PRO A 226 15.533 -97.483 -61.051 1.00 82.38 C ATOM 638 CB ARG A 232 22.190 -83.405 -54.301 1.00129.88 C

ANISOU 593 C PRO A 226 11427 8651 11222 1020 -260 671 C ANISOU 638 CB ARG A 232 17785 14814 16749 1563 -2921 -2323 C

ATOM 594 O PRO A 226 15.944 -96.452 -61.596 1.00 80.06 O ATOM 639 CG ARG A 232 22.414 -84.525 -55.308 1.00126.61 C

ANISOU 594 O PRO A 226 10906 8411 11102 1052 -333 479 O ANISOU 639 CG ARG A 232 17023 14405 16678 1532 -2808 -2070 C

ATOM 595 N GLN A 227 15.063 -97.511 -59.811 1.00 82.90 N ATOM 640 CD ARG A 232 23.728 -84.381 -56.055 1.00128.51 C

ANISOU 595 N GLN A 227 11751 8807 10941 1084 -243 779 N ANISOU 640 CD ARG A 232 16828 14531 17471 1374 -3003 -2217 C

ATOM 596 CA GLN A 227 14.912 -96.295 -59.037 1.00 73.01 C ATOM 641 NE ARG A 232 23.583 -83.816 -57.393 1.00128.05 N

ANISOU 596 CA GLN A 227 10533 7735 9474 1194 -305 660 C ANISOU 641 NE ARG A 232 16541 14324 17789 1222 -2636 -2228 N

ATOM 597 CB GLN A 227 14.103 -96.565 -57.774 1.00 76.63 C ATOM 642 CZ ARG A 232 24.433 -84.032 -58.394 1.00126.77 C

ANISOU 597 CB GLN A 227 11313 8290 9514 1237 -178 830 C ANISOU 642 CZ ARG A 232 15985 14070 18113 1112 -2596 -2206 C

ATOM 598 CG GLN A 227 12.631 -96.757 -58.045 1.00 78.01 C ATOM 643 NHl ARG A 232 24.232 -83.474 -59.579 1.00122.76 N

ANISOU 598 CG GLN A 227 11437 8589 9614 1038 208 950 C ANISOU 643 NHl ARG A 232 15332 13425 17886 1000 -2241 -2206 N

ATOM 599 CD GLN A 227 11.925 -97.465 -56.914 1.00 85.04 C ATOM 644 ΝΉ2 ARG A 232 25.489 -84.807 -58.209 1.00127.58 N

ANISOU 599 CD GLN A 227 12655 9505 10151 1044 383 1186 C ANISOU 644 ΝΉ2 ARG A 232 15849 14219 18408 1141 -2899 -2176 N

ATOM 600 OE1 GLN A 227 12.523 -98.279 -56.208 1.00 90.72 O ATOM 645 C ARG A 232 21.706 -82.977 -51.836 1.00142.51 C

ANISOU 600 OE1 GLN A 227 13660 10074 10737 1154 248 1321 O ANISOU 645 C ARG A 232 20155 16571 17423 1824 -3281 -2523 C

ATOM 601 NE2 GLN A 227 10.647 -97.155 -56.729 1.00 83.42 N ATOM 646 O ARG A 232 20.819 -83.484 -51.140 1.00144.75 O

ANISOU 601 NE2 GLN A 227 12412 9496 9787 943 700 1249 N ANISOU 646 O ARG A 232 20784 16981 17234 2009 -3143 -2342 O

ATOM 602 C GLN A 227 16.246 -95.652 -58.695 1.00 70.38 C ATOM 647 N ALA A 233 22.108 -81.716 -51.686 1.00143.11 N

ANISOU 602 C GLN A 227 10167 7359 9217 1379 -668 485 C ANISOU 647 N ALA A 233 20255 16505 17614 1696 -3381 -2861 N

ATOM 603 O GLN A 227 17.304 -96.285 -58.747 1.00 73.10 o ATOM 648 CA ALA A 233 21.492 -80.842 -50.695 1.00138.64 C

ANISOU 603 O GLN A 227 10505 7557 9711 1469 -894 503 o ANISOU 648 CA ALA A 233 20161 15926 16589 1791 -3377 -3062 C

ATOM 604 N GLN A 228 16.181 -94.376 -58.354 1.00 72.46 N ATOM 649 CB ALA A 233 22.207 -79.516 -50.625 1.00139.58 C

ANISOU 604 N GLN A 228 10398 7750 9385 1433 -718 308 N ANISOU 649 CB ALA A 233 20248 15843 16945 1594 -3582 -3476 C

ATOM 605 CA GLN A 228 17.353 -93.619 -57.983 1.00 76.24 C ATOM 650 C ALA A 233 20.032 -80.612 -50.987 1.00130.68 C

ANISOU 605 CA GLN A 228 10832 8202 9934 1562 -1060 104 C ANISOU 650 C ALA A 233 19385 14939 15328 1911 -2826 -2876 C

ATOM 606 CB GLN A 228 17.630 -92.547 -59.036 1.00 75.48 C ATOM 651 O ALA A 233 19.631 -80.498 -52.133 1.00123.83 O

ANISOU 606 CB GLN A 228 10419 8090 10171 1477 -1024 -111 C ANISOU 651 O ALA A 233 18270 14018 14763 1838 -2447 -2725 O

ATOM 607 CG GLN A 228 18.600 -91.464 -58.613 1.00 80.08 C ATOM 652 N GLY A 234 19.248 -80.601 -49.919 1.00129.16 N

ANISOU 607 CG GLN A 228 10950 8661 10815 1552 -1315 -359 C ANISOU 652 N GLY A 234 19667 14839 14568 2113 -2787 -2890 N

ATOM 608 CD GLN A 228 19.823 -91.389 -59.504 1.00 83.98 C ATOM 653 CA GLY A 234 17.868 -80.190 -49.930 1.00121.13 C

ANISOU 608 CD GLN A 228 11126 9024 11758 1516 -1475 -480 C ANISOU 653 CA GLY A 234 18884 13862 13278 2253 -2280 -2750 C

ATOM 609 OE1 GLN A 228 19.787 -91.793 -60.667 1.00 80.28 O ATOM 654 C GLY A 234 16.980 -81.324 -50.323 1.00115.06 C

ANISOU 609 OE1 GLN A 228 10459 8479 11564 1430 -1295 -417 O ANISOU 654 C GLY A 234 18018 13277 12421 2346 -1955 -2335 C

ATOM 610 NE2 GLN A 228 20.920 -90.871 -58.960 1.00 89.67 N ATOM 655 O GLY A 234 15.779 -81.266 -50.165 1.00112.28 O

ANISOU 610 NE2 GLN A 228 11792 9724 12553 1581 -1814 -660 N ANISOU 655 O GLY A 234 17846 13024 11790 2485 -1551 -2175 O

ATOM 611 C GLN A 228 17.097 -92.998 -56.619 1.00 79.11 C ATOM 656 N FLE A 235 17.585 -82.392 -50.807 1.00118.14 N

ANISOU 611 C GLN A 228 11488 8690 9882 1694 -1157 57 C ANISOU 656 N FLE A 235 18116 13712 13061 2265 -2126 -2162 N

ATOM 612 O GLN A 228 15.951 -92.758 -56.242 1.00 81.95 O ATOM 657 CA FLE A 235 16.837 -83.594 -51.079 1.00116.53 C

ANISOU 612 O GLN A 228 11996 9170 9971 1674 -894 130 O ANISOU 657 CA ILE A 235 17814 13643 12818 2307 -1838 -1784 C

ATOM 613 N THR A 229 18.163 -92.757 -55.869 1.00 80.30 N ATOM 658 CB FLE A 235 16.631 -83.752 -52.586 1.00101.63 C

ANISOU 613 N THR A 229 11717 8820 9973 1838 -1536 -68 N ANISOU 658 CB FLE A 235 15504 11702 11411 2149 -1532 -1668 C

ATOM 614 CA THR A 229 18.037 -92.144 -54.563 1.00 79.90 C ATOM 659 CGI ILE A 235 16.041 -85.107 -52.909 1.00102.57 C

ANISOU 614 CA THR A 229 11975 8877 9505 1980 -1676 -149 C ANISOU 659 CGI FLE A 235 15486 11937 11548 2141 -1318 -1311 C

ATOM 615 CB THR A 229 18.344 -93.156 -53.457 1.00 79.87 C ATOM 660 CD1 ILE A 235 15.510 -85.210 -54.320 1.00101.97 C

ANISOU 615 CB THR A 229 12300 8873 9172 2163 -1875 32 C ANISOU 660 CD1 FLE A 235 15053 11840 11850 2011 -992 -1204 C

ATOM 616 OG1 THR A 229 17.451 -94.266 -53.584 1.00 79.72 O ATOM 661 CG2 ILE A 235 17.931 -83.537 -53.315 1.00 92.37 C

ANISOU 616 OG1 THR A 229 12409 8825 9056 2107 -1546 334 O ANISOU 661 CG2 FLE A 235 13989 10357 10749 1967 -1798 -1865 C

ATOM 617 CG2 THR A 229 18.171 -92.535 -52.077 1.00 80.85 C ATOM 662 C FLE A 235 17.544 -84.794 -50.449 1.00125.11 C

ANISOU 617 CG2 THR A 229 12794 9118 8807 2330 -2013 -51 C ANISOU 662 C FLE A 235 18914 14799 13821 2357 -2152 -1626 C

ATOM 618 C THR A 229 18.940 -90.923 -54.485 1.00 87.92 C ATOM 663 O FLE A 235 18.695 -85.089 -50.748 1.00129.27 O

ANISOU 618 C THR A 229 12861 9884 10659 1994 -1974 -472 C ANISOU 663 O FLE A 235 19162 15258 14699 2258 -2463 -1682 O

ATOM 619 O THR A 229 19.990 -90.871 -55.126 1.00 88.12 O ATOM 664 N LYS A 236 16.859 -85.458 -49.540 1.00123.27 N

ANISOU 619 O THR A 229 12592 9820 11070 1947 -2183 -590 O ANISOU 664 N LYS A 236 19029 14699 13109 2532 -2052 -1423 N

ATOM 620 N FLE A 230 18.523 -89.935 -53.704 1.00 97.10 N ATOM 665 CA LYS A 236 17.371 -86.669 -48.951 1.00114.92 C

ANISOU 620 N FLE A 230 14246 11131 11516 2051 -1974 -619 N ANISOU 665 CA LYS A 236 18078 13699 11888 2630 -2295 -1230 C

ATOM 621 CA FLE A 230 19.181 -88.645 -53.709 1.00103.59 C ATOM 666 CB LYS A 236 17.898 -86.421 -47.532 1.00113.45 C

ANISOU 621 CA ILE A 230 14967 11916 12478 2015 -2183 -947 C ANISOU 666 CB LYS A 236 18312 13564 11228 2825 -2700 -1398 C

ATOM 622 C FLE A 230 19.863 -88.320 -52.399 1.00113.84 C ATOM 667 CG LYS A 236 17.834 -84.968 -47.042 1.00111.53 C

ANISOU 622 C FLE A 230 16534 13262 13458 2162 -2601 -1118 C ANISOU 667 CG LYS A 236 18275 13281 10820 2839 -2776 -1760 C

ATOM 623 O FLE A 230 19.295 -88.510 -51.324 1.00121.58 O ATOM 668 CD LYS A 236 16.484 -84.624 -46.406 1.00105.27 C

ANISOU 623 O FLE A 230 17907 14339 13949 2317 -2584 -1029 O ANISOU 668 CD LYS A 236 17892 12574 9531 3002 -2360 -1675 C ATOM 669 CE LYS A 236 15.824 -83402 -47.022 1.00 96.12 C ATOM 714 0G SER A 241 9.320 -93.568 -61.151 1.00 61.03 O

ANISOU 669 CE LYS A 236 16631 11335 8557 2914 -2029 -1841 C ANISOU 714 OG SER A 241 8221 7146 7820 747 953 583 O

ATOM 670 NZ LYS A 236 14.653 -83.764 -47.859 1.00 89.20 N ATOM 715 C SER A 241 11.537 -92.543 -62.635 1.00 66.75 C

ANISOU 670 NZ LYS A 236 15528 10526 7838 2867 -1480 -1542 N ANISOU 715 C SER A 241 8740 7566 9055 879 546 244 C

ATOM 671 C LYS A 236 16.249 -87.674 -48.930 1.00109.77 C ATOM 716 O SERA 241 11.049 -91.414 -62.683 1.00 57.48 O

ANISOU 671 C LYS A 236 17539 13141 11027 2679 -1867 -852 C ANISOU 716 O SER A 241 7501 6529 7811 965 648 154 O

ATOM 672 O LYS A 236 15.233 - 87.479 -48.277 1.00102.98 O ATOM 717 N ASN A 242 11.949 -93.201 -63.709 1.00 57.03 N

ANISOU 672 O LYS A 236 16975 12377 9775 2790 -1565 -779 O ANISOU 717 N ASN A 242 7369 6207 8091 773 514 243 N

ATOM 673 N ASP A 237 16.466 -88.792 -49.587 1.00110.51 N ATOM 718 CA ASN A 242 11.715 -92.701 -65.045 1.00 46.44 C

ANISOU 673 N ASP A 237 17388 13197 11406 2586 -1825 -621 N ANISOU 718 CA ASN A 242 5787 4909 6949 737 613 152 C

ATOM 674 CA ASP A 237 15.513 -89.845 -49.453 1.00109.66 C ATOM 719 CB ASN A 242 13.020 -92.279 -65.702 1.00 51.82 C

ANISOU 674 CA ASP A 237 17362 13143 11160 2582 -1453 -260 C ANISOU 719 CB ASN A 242 6391 5396 7900 812 451 12 C

ATOM 675 CB ASP A 237 15.250 -90.027 -47.980 1.00114.61 C ATOM 720 CG ASN A 242 13.734 -91.197 -64.936 1.00 53.93 C

ANISOU 675 CB ASP A 237 18502 13861 11186 2803 -1437 -107 C ANISOU 720 CG ASN A 242 6736 5627 8130 959 310 -114 C

ATOM 676 CG ASP A 237 16.439 -90.614 -47.285 1.00120.20 C ATOM 721 OD1 ASN A 242 14.380 -91.464 -63.925 1.00 64.35 O

ANISOU 676 CG ASP A 237 19399 14525 11747 2960 -1900 -83 C ANISOU 721 OD1 ASN A 242 8213 6875 9363 1012 121 -107 O

ATOM 677 OD2 ASP A 237 16.700 -91.804 -47.497 1.00127.13 O ATOM 722 ND2 ASN A 242 13.608 -89.958 -65.405 1.00 57.51 N

ANISOU 677 OD2 ASP A 237 20476 15390 12438 3037 -1803 224 O ANISOU 722 ND2 ASN A 242 7096 6121 8634 1028 395 -237 N

ATOM 678 OD1 ASP A 237 17.149 -89.895 -46.570 1.00119.09 O ATOM 723 C ASN A 242 11.060 -93.789 -65.861 1.00 50.51 C

ANISOU 678 OD1 ASP A 237 19201 14361 11686 3005 -2357 -367 O ANISOU 723 C ASN A 242 6208 5441 7541 544 733 248 C

ATOM 679 C ASP A 237 14.254 -89.705 -50.273 1.00102.04 C ATOM 724 O ASN A 242 11.251 -94.977 -65.592 1.00 51.19 O

ANISOU 679 C ASP A 237 16189 12237 10347 2439 -947 -162 C ANISOU 724 O ASN A 242 6420 5397 7633 442 693 355 O

ATOM 680 O ASP A 237 13.234 - 90.305 -49.986 1.00102.84 O ATOM 725 N SERA 243 10.303 -93.386 -66.869 1.00 51.20 N

ANISOU 680 O ASP A 237 16412 12426 10236 2442 -589 94 O ANISOU 725 N SER A 243 6092 5679 7683 502 870 203 N

ATOM 681 N ARG A 238 14.347 -88.889 -51.300 1.00 86.07 N ATOM 726 CA SER A 243 9.513 -94.343 -67.618 1.00 61.98 C

ANISOU 681 N ARG A 238 13848 10170 8686 2319 -912 -359 N ANISOU 726 CA SER A 243 7354 7105 9093 296 972 266 C

ATOM 682 CA ARG A 238 13.368 -88.855 -52.333 1.00 68.71 C ATOM 727 CB SER A 243 8.031 -93.970 -67.572 1.00 56.65 C

ANISOU 682 CA ARG A 238 11364 8022 6720 2178 -502 -247 C ANISOU 727 CB SER A 243 6516 6753 8254 245 1164 310 C

ATOM 683 CB ARG A 238 13.647 -87.688 -53.201 1.00 64.35 C ATOM 728 OG SER A 243 7.543 -94.042 -66.250 1.00 44.33 O

ANISOU 683 CB ARG A 238 10582 7425 6442 2125 -467 -495 C ANISOU 728 OG SER A 243 5081 5286 6475 248 1245 423 O

ATOM 684 CG ARG A 238 12.534 -86.809 -53.351 1.00 80.76 C ATOM 729 C SER A 243 9.984 -94.510 -69.050 1.0046.82 C

ANISOU 684 CG ARG A 238 12705 9636 8344 2194 -74 -492 C ANISOU 729 C SER A 243 5320 5070 7399 268 930 171 C

ATOM 685 CD ARG A 238 13.089 -85.485 -53.158 1.00 82.55 C ATOM 730 O SERA 243 10.370 -93.549 -69.712 1.00 45.92 O

ANISOU 685 CD ARG A 238 13158 9808 8401 2328 -185 -781 C ANISOU 730 O SER A 243 5115 4959 7373 411 920 65 O

ATOM 686 NE ARG A 238 12.328 -84.515 -53.878 1.00 75.31 N ATOM 731 N FLE A 244 9.922 -95.747 -69.518 1.00 45.57 N

ANISOU 686 NE ARG A 238 12048 8868 7697 2313 45 -895 N ANISOU 731 N FLE A 244 5197 4797 7320 82 928 214 N

ATOM 687 CZ ARG A 238 11.618 -83.563 -53.330 1.00 85.25 C ATOM 732 CA FLE A 244 10.367 -96.107 -70.850 1.00 50.86 C

ANISOU 687 CZ ARG A 238 13495 10183 8714 2471 276 -981 C ANISOU 732 CA ILE A 244 5815 5334 8176 49 896 128 C

ATOM 688 NH1 ARG A 238 11.037 -82.744 -54.147 1.00 68.92 N ATOM 733 CB FLE A 244 11.176 -97.394 -70.813 1.00 40.31 C

ANISOU 688 NH1 ARG A 238 11813 8200 6173 2650 324 -978 N ANISOU 733 CB FLE A 244 4665 3694 6956 -32 818 174 C

ATOM 689 ΝΉ2 ARG A 238 11.244 -83.615 -52.068 1.00 92.77 N ATOM 734 CGI ILE A 244 12.437 -97.174 -69.992 1.0040.12 C

ANISOU 689 ΝΉ2 ARG A 238 14266 11098 9883 2476 477 -1061 N ANISOU 734 CGI FLE A 244 4764 3493 6988 156 682 191 C

ATOM 690 C ARG A 238 13.680 -90.055 -53.152 1.00 67.66 C ATOM 735 CD1 ILE A 244 12.776 -98.327 -69.103 1.00 61.33 C

ANISOU 690 C ARG A 238 10977 7805 6924 2025 -530 -73 C ANISOU 735 CD1 FLE A 244 7677 5991 9635 106 622 321 C

ATOM 691 O ARG A 238 14.825 -90.420 -53.255 1.00 66.89 O ATOM 736 CG2 ILE A 244 11.525 -97.844 -72.214 1.0043.76 C

ANISOU 691 O ARG A 238 10808 7585 7023 2021 -874 -141 O ANISOU 736 CG2 FLE A 244 5074 3995 7556 -68 815 80 C

ATOM 692 N VAL A 239 12.675 -90.651 -53.757 1.00 62.98 N ATOM 737 C FLE A 244 9.170 -96.318 -71.745 1.0045.97 C

ANISOU 692 N VAL A 239 10250 7281 6398 1903 -174 144 N ANISOU 737 C FLE A 244 5030 4923 7513 -112 992 100 C

ATOM 693 CA VAL A 239 12.877 -91.768 -54.633 1.00 61.13 C ATOM 738 O FLE A 244 8.204 -96.977 -71.362 1.00 43.32 O

ANISOU 693 CA VAL A 239 9796 6947 6483 1742 -166 291 C ANISOU 738 O FLE A 244 4671 4707 7083 -316 1064 176 O

ATOM 694 CB VAL A 239 12.141 -92.992 -54.166 1.00 67.70 C ATOM 739 N TYR A 245 9.235 -95.767 -72.947 1.00 42.32 N

ANISOU 694 CB VAL A 239 10808 7802 7113 1693 51 596 C ANISOU 739 N TYR A 245 4450 4510 7118 -24 994 -8 N

ATOM 695 CGI VAL A 239 12.298 -94.081 -55.154 1.00 61.52 C ATOM 740 CA TYR A 245 8.122 -95.871 -73.861 1.00 45.39 C

ANISOU 695 CGI VAL A 239 9805 6891 6680 1502 94 720 C ANISOU 740 CA TYR A 245 4667 5132 7446 -142 1043 -55 C

ATOM 696 CG2 VAL A 239 12.667 -93.440 -52.841 1.00 66.47 C ATOM 741 CB TYR A 245 7.534 -94.497 -74.140 1.00 44.07 C

ANISOU 696 CG2 VAL A 239 11066 7606 6586 1883 -159 679 C ANISOU 741 CB TYR A 245 4319 5248 7178 59 1104 -89 C

ATOM 697 C VAL A 239 12.354 -91.369 -55.966 1.00 71.40 C ATOM 742 CG TYR A 245 6.857 -93.926 -72.929 1.00 51.54 C

ANISOU 697 C VAL A 239 10722 8277 8130 1582 50 245 C ANISOU 742 CG TYR A 245 5208 6396 7978 104 1183 -2 C

ATOM 698 O VAL A 239 11.300 -90.834 -56.061 1.00 75.06 O ATOM 743 CD1 TYR A 245 7.597 -93.313 -71.917 1.00 55.10 C

ANISOU 698 O VAL A 239 11115 8899 8507 1546 371 304 O ANISOU 743 CD 1 TYR A 245 5802 6720 8414 259 1173 26 C

ATOM 699 N TYR A 240 13.108 -91.620 -57.012 1.00 72.90 N ATOM 744 CE1 TYR A 245 6.981 -92.802 -70.799 1.00 51.82 C

ANISOU 699 N TYR A 240 10667 8328 8703 1505 -124 142 N ANISOU 744 CE1 TYR A 245 5380 6478 7833 317 1255 96 C

ATOM 700 CA TYR A 240 12.701 -91.220 -58.340 1.00 73.01 C ATOM 745 CZ TYR A 245 5.601 -92.907 -70.679 1.00 57.80 C

ANISOU 700 CA TYR A 240 10354 8359 9027 1378 57 94 C ANISOU 745 CZ TYR A 245 5950 7551 8459 222 1374 157 C

ATOM 701 CB TYR A 240 13.734 -90.307 -58.944 1.00 58.93 C ATOM 746 OH TYR A 245 4.968 -92.399 -69.568 1.00 62.60 O

ANISOU 701 CB TYR A 240 8405 6462 7525 1405 -133 -145 C ANISOU 746 OH TYR A 245 6555 8339 8893 302 1493 235 O

ATOM 702 CG TYR A 240 13.712 -88.916 -58.444 1.00 54.44 C ATOM 747 CE2 TYR A 245 4.847 -93.517 -71.668 1.00 64.11 C

ANISOU 702 CG TYR A 240 7957 5939 6790 1525 -151 -332 C ANISOU 747 CE2 TYR A 245 6558 8501 9301 48 1375 132 C

ATOM 703 CD2 TYR A 240 13.063 -87.934 -59.138 1.00 52.37 C ATOM 748 CD2 TYR A 245 5.478 -94.025 -72.778 1.00 62.26 C

ANISOU 703 CD2 TYR A 240 7573 5744 6583 1536 83 -409 C ANISOU 748 CD2 TYR A 245 6367 8079 9210 -14 1267 45 C

ATOM 704 CE2 TYR A 240 13.052 -86.669 -58.701 1.00 52.09 C ATOM 749 C TYR A 245 8.498 -96.575 -75.147 1.00 54.37 C

ANISOU 704 CE2 TYR A 240 7687 5712 6393 1658 87 -584 C ANISOU 749 C TYR A 245 5856 6110 8693 -212 993 -149 C

ATOM 705 CZ TYR A 240 13.709 -86.364 -57.565 1.00 72.81 C ATOM 750 O TYR A 245 9.658 -96.594 -75.556 1.00 56.14 O

ANISOU 705 CZ TYR A 240 10584 8284 8797 1748 -166 -704 C ANISOU 750 O TYR A 245 6204 6078 9050 -87 958 -190 O

ATOM 706 OH TYR A 240 13.712 -85.101 -57.105 1.00 72.59 O ATOM 751 N GLU A 246 7.492 -97.170 -75.765 1.00 56.22 N

ANISOU 706 OH TYR A 240 10745 8232 8604 1859 -167 -903 O ANISOU 751 N GLU A 246 5987 6504 8871 -420 994 -191 N

ATOM 707 CE1 TYR A 240 14.370 -87.320 -56.860 1.00 74.81 C ATOM 752 CA GLU A 246 7.652 -97.872 -77.011 1.0049.56 C

ANISOU 707 CE1 TYR A 240 10945 8501 8977 1744 -427 -632 C ANISOU 752 CA GLU A 246 5209 5540 8084 -508 940 -304 C

ATOM 708 CD1 TYR A 240 14.372 -88.573 -57.297 1.00 62.68 C ATOM 753 CB GLU A 246 6.878 -99.179 -76.942 1.00 68.75 C

ANISOU 708 CD1 TYR A 240 9262 6952 7603 1644 -408 -436 C ANISOU 753 CB GLU A 246 7660 7954 10507 -869 925 -309 C

ATOM 709 C TYR A 240 12.606 -92.382 -59.262 1.00 79.47 C ATOM 754 CG GLU A 246 6.783 -99.964 -78.227 1.00 89.25 C

ANISOU 709 C TYR A 240 11021 9109 10066 1213 142 250 C ANISOU 754 CG GLU A 246 10325 10461 13123 -1013 855 -457 C

ATOM 710 O TYR A 240 13.258 -93.372 -59.087 1.00 78.87 O ATOM 755 CD GLU A 246 5.777-101.091 -78.101 1.00101.26 C

ANISOU 710 O TYR A 240 11034 8889 10043 1207 -24 335 O ANISOU 755 CD GLU A 246 11815 12024 14635 -1416 844 -478 C

ATOM 711 N SERA 241 11.791 -92.245 -60.275 1.00 79.90 N ATOM 756 OE1 GLU A 246 5.414-101.693 -79.133 1.00101.76 O

ANISOU 711 N SER A 241 10855 9264 10238 1092 395 282 N ANISOU 756 OE1 GLU A 246 11895 12086 14686 -1586 766 -629 C

ATOM 712 CA SER A 241 11.721 -93.257 -61.304 1.00 79.70 C ATOM 757 OE2 GLU A 246 5.356-101.362 -76.960 1.00103.92 O

ANISOU 712 CA SER A 241 10667 9161 10453 919 458 370 C ANISOU 757 OE2 GLU A 246 12122 12391 14973 -1569 921 -347 C

ATOM 713 CB SER A 241 10.567 -94.228 -61.051 1.00 72.20 C ATOM 758 C GLU A 246 7.062 -96.962 -78.063 1.00 52.61 C

ANISOU 713 CB SER A 241 9773 8310 9349 769 699 579 C ANISOU 758 C GLU A 246 5411 6208 8371 -364 933 -393 C

 ATOM 849 CG LEU A 259 8.977 -89.616 -74.331 1.00 53.35 C ATOM 894 N LEU A 265 6.159 -76.822 -67.425 1.00 35.30 N

ANISOU 849 CG LEU A 259 7238 5572 7460 724 -126 -821 C ANISOU 894 N LEU A 265 5100 3401 4910 -509 425 -596 N

ATOM 850 CD1 LEU A 259 9.952 -88.891 -75.223 1.00 56.32 C ATOM 895 CA LEU A 265 5.080 -76.452 -68.332 1.00 46.00 C

ANISOU 850 CD1 LEU A 259 7825 6009 7564 786 -142 -777 C ANISOU 895 CA LEU A 265 6226 4945 6307 -580 326 -673 C

ATOM 851 CD2 LEU A 259 8.019 -90.435 -75.175 1.00 49.92 C ATOM 896 CB LEU A 265 5.082 -77.311 -69.588 1.00 36.83 C

ANISOU 851 CD2 LEU A 259 6795 4988 7186 796 -305 -969 C ANISOU 896 CB LEU A 265 5139 3802 5053 -647 248 -764 C

ATOM 852 C LEU A 259 9.683 -89.405 -71.159 1.00 42.59 C ATOM 897 CG LEU A 265 6.321 -77.225 -70.467 1.00 41.47 C

ANISOU 852 C LEU A 259 5572 4457 6154 448 286 -557 C ANISOU 897 CG LEU A 265 5865 4364 5529 -459 184 -678 C

ATOM 853 O LEU A 259 8.977 -90.102 -70.437 1.00 50.93 O ATOM 898 CD1 LEU A 265 6.036 -77.958 -71.741 1.00 51.11 C

ANISOU 853 O LEU A 259 6459 5487 7404 380 315 -570 O ANISOU 898 CD1 LEU A 265 7124 5658 6636 -514 91 -806 C

ATOM 854 N GLU A 260 9.708 -88.082 -71.058 1.00 37.71 N ATOM 899 CD2 LEU A 265 6.727 -75.780 -70.770 1.00 25.97 C

ANISOU 854 N GLU A 260 5007 3893 5429 443 288 -563 N ANISOU 899 CD2 LEU A 265 3749 2510 3607 -243 114 -533 C

ATOM 855 CA GLU A 260 8.866 -87.404 -70.083 1.00 57.14 C ATOM 900 C LEU A 265 3.740 -76.575 -67.609 1.00 43.44 C

ANISOU 855 CA GLU A 260 7322 6384 8006 364 328 -610 C ANISOU 900 C LEU A 265 5748 4678 6079 -756 411 -756 C

ATOM 856 CB GLU A 260 9.445 -87.537 -68.673 1.00 37.08 C ATOM 901 O LEU A 265 2.800 -75.829 -67.887 1.00 47.75 O

ANISOU 856 CB GLU A 260 4670 3987 5432 225 533 -477 C ANISOU 901 O LEU A 265 6037 5407 6699 -759 341 -791 O

ATOM 857 CG GLU A 260 10.743 -86.792 -68.432 1.00 49.66 C ATOM 902 N GLN A 266 3.653 -77.533 -66.691 1.00 38.33 N

ANISOU 857 CG GLU A 260 6373 5703 6791 196 639 -346 C ANISOU 902 N GLN A 266 5255 3873 5434 -889 579 -770 N

ATOM 858 CD GLU A 260 11.408 -87.203 -67.124 1.00 69.53 C ATOM 903 CA GLN A 266 2.468 -77.680 -65.849 1.0041.70 C

ANISOU 858 CD GLU A 260 8788 8356 9274 56 825 -196 C ANISOU 903 CA GLN A 266 5549 4332 5963 -1047 719 -813 C ATOM 859 OE1 GLU A 260 11.289 -88.393 -66.741 1.00 69.55 O ATOM 904 C GLN A 266 2.248 -76.399 -65.077 1.00 50.69 C

ANISOU 859 OE1 GLU A 260 8687 8347 9392 7 864 -147 O ANISOU 904 C GLN A 266 6533 5587 7141 -893 725 -751 C ATOM 860 OE2 GLU A 260 12.031 -86.331 -66.479 1.00 78.26 O ATOM 905 O GLN A 266 1.128 -75.893 -64.974 1.00 45.72 O ANISOU 860 OE2 GLU A 260 9915 9576 10243 -9 921 -126 O ANISOU 905 O GLN A 266 5651 5107 6612 -948 738 -798 O

ATOM 861 C GLU A 260 8.607 -85.938 -70.419 1.00 49.86 C ATOM 906 CB GLN A 266 2.617 -78.825 -64.853 1.00 32.58 C

ANISOU 861 C GLU A 260 6475 5451 7018 405 247 -678 C ANISOU 906 CB GLN A 266 4631 2961 4785 -1154 943 -776 C

ATOM 862 O GLU A 260 9.412 -85.282 -71.081 1.00 53.54 O ATOM 907 CG GLN A 266 2.163 -80.177 -65.355 1.0046.50 C

ANISOU 862 O GLU A 260 7107 5941 7294 457 216 -627 O ANISOU 907 CG GLN A 266 6465 4594 6611 -1406 1013 -879 C

ATOM 863 N TYR A 261 7.465 -85.440 -69.962 1.00 40.46 N ATOM 908 CD GLN A 266 2.512 -81.291 -64.382 1.00 56.89 C

ANISOU 863 N TYR A 261 5152 4220 6001 380 211 -793 N ANISOU 908 CD GLN A 266 8067 5649 7899 -1464 1259 -793 C

ATOM 864 CA TYR A 261 7.144 -84.027 -70.083 1.00 41.00 C ATOM 909 OE1 GLN A 266 1.787 -81.532 -63.421 1.00 59.31 O

ANISOU 864 CA TYR A 261 5253 4270 6054 407 142 -863 C ANISOU 909 OE1 GLN A 266 8626 5804 8106 -1393 1253 -753 O

ATOM 865 CB TYR A 261 5.662 -83.785 -69.851 1.00 39.58 C ATOM 910 NE2 GLN A 266 3.615 -81.994 -64.644 1.00 50.56 N

ANISOU 865 CB TYR A 261 4912 3997 6132 408 60 -1026 C ANISOU 910 NE2 GLN A 266 7217 4827 7166 -1544 1479 -733 N

ATOM 866 CG TYR A 261 4.799 -84.140 -71.026 1.00 67.12 C ATOM 911 N THR A 267 3.341 -75.889 -64.524 1.00 36.15 N

ANISOU 866 CG TYR A 261 8437 7318 9747 514 -161 -1135 C ANISOU 911 N THR A 267 4838 3669 5230 -695 712 -663 N ATOM 867 CD1 TYR A 261 4.609 -83.233 -72.064 1.00 41.08 C ATOM 912 CA THR A 267 3.303 -74.644 -63.789 1.00 33.16 C ANISOU 867 CD1 TYR A 261 5267 3927 6413 607 -351 -1188 C ANISOU 912 CA THR A 267 4342 3365 4891 -532 700 -635 C

ATOM 868 CE1 TYR A 261 3.826 -83.546 -73.147 1.0046.60 C ATOM 913 CB THR A 267 4.624 -74.358 -63.088 1.00 27.38 C

ANISOU 868 CE1 TYR A 261 6009 4481 7217 696 -566 -1282 C ANISOU 913 CB THR A 267 3802 2517 4085 -345 681 -577 C

ATOM 869 CZ TYR A 261 3.220 -84.791 -73.209 1.00 47.70 C ATOM 914 OG1 THR A 267 4.835 -75.338 -62.072 1.00 28.48 O

ANISOU 869 CZ TYR A 261 6059 4558 7509 698 -592 -1334 C ANISOU 914 OG1 THR A 267 4168 2544 4108 -376 838 -553 O

ATOM 870 OH TYR A 261 2.435 -85.114 -74.289 1.0047.41 O ATOM 915 CG2 THR A 267 4.601 -72.954 -62.467 1.00 22.52 C

ANISOU 870 OH TYR A 261 6065 4373 7577 783 -817 -1433 O ANISOU 915 CG2 THR A 267 3046 1967 3542 -176 632 -593 C

ATOM 871 CE2 TYR A 261 3.402 -85.717 -72.192 1.00 51.22 C ATOM 916 C THR A 267 2.894 -73.465 -64.677 1.00 24.06 C

ANISOU 871 CE2 TYR A 261 6370 5085 8005 609 -405 -1279 C ANISOU 916 C THR A 267 2932 2371 3839 -448 547 -643 C ATOM 872 CD2 TYR A 261 4.184 -85.386 -71.111 1.00 41.20 C ATOM 917 O THR A 267 2.053 -72.659 -64.291 1.00 35.64 O ANISOU 872 CD2 TYR A 261 5063 3969 6622 515 -193 -1176 C ANISOU 917 O THR A 267 4202 3949 5390 -412 568 -666 O

ATOM 873 C TYR A 261 7.929 -83.193 -69.090 1.00 37.67 C ATOM 918 N LEU A 268 3.485 -73.368 -65.864 1.00 27.55 N

ANISOU 873 C TYR A 261 4821 3991 5500 318 306 -775 C ANISOU 918 N LEU A 268 3384 2823 4262 -395 410 -611 N

ATOM 874 O TYR A 261 8.149 -83.610 -67.954 1.00 41.68 O ATOM 919 CA LEU A 268 3.108 -72.323 -66.814 1.00 30.13 C

ANISOU 874 O TYR A 261 5213 4608 6014 208 477 -713 O ANISOU 919 CA LEU A 268 3491 3300 4659 -289 280 -584 C

ATOM 875 N ALA A 262 8.338 -82.004 -69.517 1.00 43.51 N ATOM 920 CB LEU A 268 3.935 -72.390 -68.107 1.00 22.85 C

ANISOU 875 N ALA A 262 5680 4729 6122 359 246 -765 N ANISOU 920 CB LEU A 268 2642 2375 3667 -206 168 -519 C

ATOM 876 CA ALA A 262 8.974 -81.065 -68.614 1.00 37.57 C ATOM 921 CG LEU A 268 5.362 -71.851 -68.073 1.00 32.15 C

ANISOU 876 CA ALA A 262 4916 4093 5267 280 377 -707 C ANISOU 921 CG LEU A 268 3939 3412 4864 -37 156 -405 C

ATOM 877 CB ALA A 262 9.635 -79.928 -69.378 1.00 36.69 C ATOM 922 CD1 LEU A 268 6.010 -71.993 -69.439 1.00 25.64 C

ANISOU 877 CB ALA A 262 4975 3961 5003 341 284 -661 C ANISOU 922 CD1 LEU A 268 3169 2616 3959 44 82 -327 C

ATOM 878 C ALA A 262 7.918 -80.527 -67.660 1.00 46.72 C ATOM 923 CD2 LEU A 268 5.408 -70.385 -67.643 1.00 20.92 C

ANISOU 878 C ALA A 262 5887 5251 6613 221 418 -845 C ANISOU 923 CD2 LEU A 268 2367 1980 3602 117 143 -346 C

ATOM 879 O ALA A 262 6.958 -79.880 -68.079 1.00 38.37 O ATOM 924 C LEU A 268 1.611 -72.387 -67.138 1.00 41.27 C

ANISOU 879 O ALA A 262 4794 4076 5709 282 278 -983 O ANISOU 924 C LEU A 268 4661 4901 6119 -409 266 -670 C

ATOM 880 N THR A 263 8.105 -80.801 -66.374 1.00 35.15 N ATOM 925 O LEU A 268 0.943 -71.358 -67.274 1.00 44.67 O

ANISOU 880 N THR A 263 5895 2823 4636 -587 750 -531 N ANISOU 925 O LEU A 268 4868 5468 6636 -306 217 -653 O

ATOM 881 CA THR A 263 7.187 -80.360 -65.329 1.00 32.79 C ATOM 926 N PHE A 269 1.086 -73.601 -67.255 1.00 34.51 N

ANISOU 881 CA THR A 263 5520 2526 4413 -679 858 -542 C ANISOU 926 N PHE A 269 3839 4043 5229 -625 311 -769 N

ATOM 882 CB THR A 263 7.637 -80.873 -63.949 1.00 40.95 C ATOM 927 CA PHE A 269 -0.334 -73.774 -67.535 1.00 33.62 C

ANISOU 882 CB THR A 263 6718 3485 5357 -581 995 -424 C ANISOU 927 CA PHE A 269 3465 4110 5198 -772 293 -879 C ATOM 883 OG1 THR A 263 8.964 -80.417 -63.674 1.00 50.25 O ATOM 928 CB PHE A 269 -0.671 -75.211 -67.913 1.00 30.59 C ANISOU 883 OG1 THR A 263 7938 4709 6446 -336 891 -336 O ANISOU 928 CB PHE A 269 3144 3676 4801 -1028 313 -1010 C ATOM 884 CG2 THR A 263 7.627 -82.387 -63.945 1.00 26.95 C ATOM 929 CG PHE A 269 -2.055 -75.365 -68.455 1.00 42.66 C ANISOU 884 CG2 THR A 263 5102 1599 3538 -666 1112 -400 C ANISOU 929 CG PHE A 269 4362 5412 6432 -1181 237 -1158 C

ATOM 885 C THR A 263 6.883 -78.853 -65.249 1.00 35.95 C ATOM 930 CD1 PHE A 269 -2.317 -75.054 -69.782 1.00 37.97 C

ANISOU 885 C THR A 263 5671 3107 4881 -593 751 -542 C ANISOU 930 CD1 PHE A 269 3620 5029 5778 -1100 2 -1225 C

ATOM 886 O THR A 263 5.768 -78.488 -64.874 1.00 53.48 O ATOM 931 CE1 PHE A 269 -3.597 -75.163 -70.300 1.00 42.36 C

ANISOU 886 O THR A 263 7716 5425 7180 -696 795 -584 O ANISOU 931 CE1 PHE A 269 3859 5812 6424 -1221 -107 -1383 C

ATOM 887 N PRO A 264 7.862 -77.972 -65.570 1.00 35.75 N ATOM 932 CZ PHE A 269 -4.651 -75.585 -69.475 1.00 49.01 C

ANISOU 887 N PRO A 264 5606 3131 4845 -396 623 -483 N ANISOU 932 CZ PHE A 269 4506 6656 7462 -1452 45 -1469 C

ATOM 888 CA PRO A 264 7.516 -76.556 -65.415 1.00 25.13 C ATOM 933 CE2 PHE A 269 -4.405 -75.889 -68.135 1.00 41.41 C

ANISOU 888 CA PRO A 264 4021 1933 3596 -315 540 -477 C ANISOU 933 CE2 PHE A 269 3702 5469 6564 -1533 319 -1375 C

ATOM 889 CB PRO A 264 8.826 -75.841 -65.726 1.00 34.16 C ATOM 934 CD2 PHE A 269 -3.107 -75.768 -67.634 1.00 35.26 C

ANISOU 889 CB PRO A 264 5168 3055 4757 -116 437 -400 C ANISOU 934 CD2 PHE A 269 3262 4483 5653 -1383 400 -1223 C

ATOM 890 CG PRO A 264 9.877 -76.821 -65.342 1.00 32.72 C ATOM 935 C PHE A 269 -1.207 -73.343 -66.352 1.00 45.00 C

ANISOU 890 CG PRO A 264 5238 2725 4471 -60 492 -362 C ANISOU 935 C PHE A 269 4751 5594 6753 -796 444 -882 C

ATOM 891 CD PRO A 264 9.314 -78.139 -65.771 1.00 30.82 C ATOM 936 O PHE A 269 -2.189 -72.610 -66.518 1.00 44.41 O

ANISOU 891 CD PRO A 264 5140 2415 4156 -228 581 -409 C ANISOU 936 O PHE A 269 4393 5710 6770 -753 398 -908 O

ATOM 892 C PRO A 264 6.433 -76.066 -66.372 1.00 28.16 C ATOM 937 N ALA A 270 -0.842 -73.809 -65.162 1.00 29.37 N

ANISOU 892 C PRO A 264 4169 2480 4052 -403 462 -535 C ANISOU 937 N ALA A 270 2963 3447 4748 -839 631 -848 N

ATOM 893 O PRO A 264 5.874 -74.988 -66.165 1.00 37.68 O ATOM 938 CA ALA A 270 -1.561 -73.462 -63.944 1.00 33.76 C

ANISOU 893 O PRO A 264 5171 3800 5346 -353 424 -533 O ANISOU 938 CA ALA A 270 3422 4037 5368 -831 809 -840 C ATOM 939 CB ALA A 270 -0.896 -74.060 -62.726 1.00 29.89 C ATOM 984 CA GLN A 276 -3.760 -64.673 -58.863 1.00 42.55 C

ANISOU 939 CB ALA A 270 3218 3359 4778 -826 997 -782 C ANISOU 984 CA GLN A 276 3805 5467 6895 683 1093 -1007 C

ATOM 940 C ALA A 270 -1.659 -71.952 -63.795 1.00 39.87 C ATOM 985 CB GLN A 276 -3.732 -65.543 -57.653 1.00 34.61 C

ANISOU 940 C ALA A 270 4041 4918 6191 -595 735 -807 C ANISOU 985 CB GLN A 276 2998 4456 5696 622 1283 -1042 C

ATOM 941 O ALA A 270 -2.739 -71.413 -63.559 1.00 31.21 O ATOM 986 CG GLN A 276 -4.081 -64.747 -56.456 1.00 60.34 C

ANISOU 941 O ALA A 270 2691 3973 5193 -582 783 -838 O ANISOU 986 CG GLN A 276 6277 7748 8903 833 1426 -1142 C

ATOM 942 N MET A 271 -0.515 -71.285 -63.938 1.00 27.67 N ATOM 987 CD GLN A 276 -3.112 -64.904 -55.350 1.00 65.48 C

ANISOU 942 N MET A 271 2640 3277 4597 -409 629 -746 N ANISOU 987 CD GLN A 276 7248 8273 9357 942 1426 -1224 C

ATOM 943 CA MET A 271 -0.426 -69.837 -63.818 1.00 37.35 C ATOM 988 OE1 GLN A 276 -2.957 -65.974 -54.819 1.00 74.85 O

ANISOU 943 CA MET A 271 3754 4536 5901 -184 564 -716 C ANISOU 988 OE1 GLN A 276 8618 9471 10350 859 1557 -1180 O

ATOM 944 CB MET A 271 0.997 -69.357 -64.075 1.00 25.21 C ATOM 989 NE2 GLN A 276 -2.489 -63.825 -54.962 1.00 65.53 N

ANISOU 944 CB MET A 271 2389 2845 4345 -38 459 -652 C ANISOU 989 NE2 GLN A 276 7323 8153 9422 1135 1275 -1345 N

ATOM 945 CG MET A 271 1.999 -69.856 -63.055 1.00 41.28 C ATOM 990 C GLN A 276 -2.363 -64.578 -59.457 1.00 35.73 C

ANISOU 945 CG MET A 271 4689 4714 6283 -29 532 -663 C ANISOU 990 C GLN A 276 3124 4415 6039 692 901 -976 C

ATOM 946 SD MET A 271 3.679 -69.322 -63.408 1.00 38.90 S ATOM 991 0 GLN A 276 -1.577 -63.792 -59.024 1.00 39.31 O

ANISOU 946 SD MET A 271 4528 4245 6007 122 400 -603 S ANISOU 991 O GLN A 276 3690 4713 6532 849 834 -1041 O

ATOM 947 CE MET A 271 3.540 -67.565 -63.054 1.00 24.01 C ATOM 992 N ALA A 277 -2.062 -65.441 -60.396 1.00 34.12 N

ANISOU 947 CE MET A 271 2466 2346 4312 322 356 -628 C ANISOU 992 N ALA A 277 2938 4220 5806 522 818 -891 N

ATOM 948 C MET A 271 -1.400 -69.136 -64.757 1.00 28.37 C ATOM 993 CA ALA A 277 -0.841 -65.389 -61.124 1.00 28.62 C

ANISOU 948 C MET A 271 2319 3596 4865 -135 460 -715 C ANISOU 993 CA ALA A 277 2401 3363 5112 527 665 -841 C

ATOM 949 O MET A 271 -1.980 -68.109 -64.417 1.00 33.88 O ATOM 994 CB ALA A 277 -0.651 -66.633 -61.947 1.00 33.53 C

ANISOU 949 O MET A 271 2847 4367 5661 5 479 -714 O ANISOU 994 CB ALA A 277 3099 4009 5631 320 634 -777 C

ATOM 950 N SERA 272 -1.574 -69.695 -65.947 1.00 34.24 N ATOM 995 C ALA A 277 -0.739 -64.163 -61.981 1.00 48.08 C

ANISOU 950 N SER A 272 3006 4433 5572 -226 342 -722 N ANISOU 995 C ALA A 277 4728 5784 7755 680 537 -777 C

ATOM 951 CA SER A 272 -2.434 -69.087 -66.946 1.00 30.27 C ATOM 996 0 ALA A 277 0.345 -63.802 -62.357 1.00 48.44 O

ANISOU 951 CA SER A 272 2231 4150 5122 -146 209 -718 C ANISOU 996 O ALA A 277 4881 5665 7858 734 439 -732 O

ATOM 952 CB SER A 272 -2.214 -69.725 -68.324 1.00 36.09 C ATOM 997 N GLY A 278 -1.852 -63.546 -62.328 1.00 36.07 N

ANISOU 952 CB SER A 272 2998 4965 5749 -198 46 -729 C ANISOU 997 N GLY A 278 2961 4411 6333 758 551 -755 N

ATOM 953 0G SER A 272 -2.716 -71.050 -68.375 1.00 31.80 O ATOM 998 CA GLY A 278 -1.853 -62.397 -63.219 1.00 30.45 C

ANISOU 953 OG SER A 272 2453 4451 5180 -464 70 -866 O ANISOU 998 CA GLY A 278 2117 3668 5786 936 455 -660 C

ATOM 954 C SER A 272 -3.903 -69.215 -66.546 1.00 32.65 C ATOM 999 C GLY A 278 -1.139 -62.697 -64.521 1.00 41.10 C

ANISOU 954 C SER A 272 2252 4634 5519 -254 281 -812 C ANISOU 999 C GLY A 278 3517 4992 7108 896 331 -524 C

ATOM 955 O SERA 272 -4.752 -68.492 -67.055 1.00 39.74 O ATOM 1000 O GLY A 278 -0.367 -61.887 -65.030 1.00 57.64 O

ANISOU 955 O SER A 272 2880 5732 6487 -141 194 -809 O ANISOU 1000 O GLY A 278 5676 6937 9286 1010 272 -420 O

ATOM 956 N GLN A 273 -4.215 -70.115 -65.642 1.00 35.83 N ATOM 1001 N PHE A 279 -1.405 -63.875 -65.062 1.00 30.09 N

ANISOU 956 N GLN A 273 2710 4971 5933 -461 455 -881 N ANISOU 1001 N PHE A 279 2125 3745 5564 717 302 -518 N

ATOM 957 CA GLN A 273 -5.577 -70.399 -65.279 1.00 35.92 C ATOM 1002 CA PHE A 279 -0.601 -64.445 -66.123 1.00 36.68 C

ANISOU 957 CA GLN A 273 2441 5143 6063 -610 560 -966 C ANISOU 1002 CA PHE A 279 3073 4552 6311 658 204 -427 C

ATOM 958 CB GLN A 273 -5.818 -71.889 -65.233 1.00 37.14 C ATOM 1003 CB PHE A 279 0.062 -65.696 -65.570 1.00 39.04 C

ANISOU 958 CB GLN A 273 2652 5231 6229 -926 653 -1054 C ANISOU 1003 CB PHE A 279 3595 4765 6472 462 249 -500 C

ATOM 959 CG GLN A 273 -5.391 -72.620 -66.466 1.00 61.16 C ATOM 1004 CG PHE A 279 1.154 -66.257 -66.424 1.00 25.35 C

ANISOU 959 CG GLN A 273 5766 8273 9199 -1028 454 -1122 C ANISOU 1004 CG PHE A 279 2028 2948 4654 425 174 -422 C

ATOM 960 CD GLN A 273 -6.433 -72.667 -67.531 1.00 62.36 C ATOM 1005 CD1 PHE A 279 2.365 -65.578 -66.567 1.00 31.27 C

ANISOU 960 CD GLN A 273 5566 8699 9428 -1081 264 -1246 C ANISOU 1005 CD1 PHE A 279 2880 3510 5492 551 147 -335 C

ATOM 961 OE1 GLN A 273 -6.305 -72.045 -68.567 1.00 69.29 O ATOM 1006 CE1 PHE A 279 3.414 -66.114 -67.341 1.00 23.25 C

ANISOU 961 OE1 GLN A 273 6211 9662 10453 -1313 328 -1371 O ANISOU 1006 CE1 PHE A 279 2010 2424 4402 530 104 -252 C

ATOM 962 NE2 GLN A 273 -7.470 -73.429 -67.286 1.00 52.67 N ATOM 1007 CZ PHE A 279 3.240 -67.355 -67.971 1.00 30.38 C

ANISOU 962 NE2 GLN A 273 4284 7619 8108 -857 34 -1207 N ANISOU 1007 CZ PHE A 279 2985 3438 5121 391 75 -275 C

ATOM 963 C GLN A 273 -5.968 -69.850 -63.961 1.00 36.39 C ATOM 1008 CE2 PHE A 279 2.014 -68.051 -67.811 1.00 40.84 C

ANISOU 963 C GLN A 273 2455 5191 6183 -514 770 -939 C ANISOU 1008 CE2 PHE A 279 4215 4930 6374 245 88 -386 C

ATOM 964 0 GLN A 273 -7.099 -69.851 -63.653 1.00 41.14 O ATOM 1009 CD2 PHE A 279 0.994 -67.490 -67.035 1.00 25.44 C

ANISOU 964 O GLN A 273 2782 5948 6900 -575 876 -985 O ANISOU 1009 CD2 PHE A 279 2094 3054 4518 260 144 -449 C

ATOM 965 N TYR A 274 -5.024 -69.388 -63.177 1.00 37.13 N ATOM 1010 C PHE A 279 -1.519 -64.819 -67.271 1.00 43.93 C

ANISOU 965 N TYR A 274 2806 5107 6194 -359 830 -879 N ANISOU 1010 C PHE A 279 3812 5722 7156 629 112 -393 C

ATOM 966 CA TYR A 274 -5.325 -68.740 -61.907 1.00 35.08 C ATOM 1011 O PHE A 279 -2.354 -65.709 -67.124 1.0044.45 O

ANISOU 966 CA TYR A 274 2537 4839 5952 -224 1009 -879 C ANISOU 1011 O PHE A 279 3792 5943 7156 456 131 -497 O

ATOM 967 CB TYR A 274 -4.444 -69.261 -60.781 1.00 34.04 C ATOM 1012 N SER A 280 -1.391 -64.144 -68.407 1.00 29.85 N

ANISOU 967 CB TYR A 274 2741 4516 5678 -228 1156 -862 C ANISOU 1012 N SER A 280 1963 3988 5390 804 14 -252 N

ATOM 968 CG TYR A 274 -4.632 -70.717 -60.499 1.00 53.48 C ATOM 1013 CA SER A 280 -2.302 -64.403 -69.511 1.00 34.02 C

ANISOU 968 CG TYR A 274 5302 6925 8094 -482 1319 -853 C ANISOU 1013 CA SER A 280 2308 4797 5821 826 -107 -236 C

ATOM 969 CD1 TYR A 274 -5.865 -71.205 -60.091 1.00 61.20 C ATOM 1014 CB SER A 280 -2.506 -63.162 -70.385 1.00 35.78 C

ANISOU 969 CD1 TYR A 274 6070 8014 9168 -635 1524 -869 C ANISOU 1014 CB SER A 280 2400 5088 6106 1125 -169 -58 C

ATOM 970 CE1 TYR A 274 -6.050 -72.544 -59.832 1.00 66.25 C ATOM 1015 OG SER A 280 -1.302 -62.815 -71.036 1.00 57.27 O

ANISOU 970 CE1 TYR A 274 6799 8564 9810 -883 1705 -849 C ANISOU 1015 OG SER A 280 5303 7638 8818 1241 -170 112 O

ATOM 971 CZ TYR A 274 -4.986 -73.418 -59.985 1.00 60.65 C ATOM 1016 C SER A 280 -1.837 -65.577 -70.364 1.00 36.98 C

ANISOU 971 CZ TYR A 274 6409 7653 8982 -959 1670 -815 C ANISOU 1016 C SER A 280 2817 5227 6005 685 -197 -262 C

ATOM 972 0H TYR A 274 -5.150 -74.757 -59.733 1.00 63.90 O ATOM 1017 O SER A 280 -0.692 -66.025 -70.266 1.00 44.22 O

ANISOU 972 OH TYR A 274 6930 7935 9416 -1196 1866 -784 O ANISOU 1017 O SER A 280 3974 5953 6875 620 -159 -237 O

ATOM 973 CE2 TYR A 274 -3.750 -72.958 -60.391 1.00 54.23 C ATOM 1018 N ARG A 281 -2.734 -66.061 -71.215 1.00 46.62 N

ANISOU 973 CE2 TYR A 274 5799 6753 8052 -794 1456 -803 C ANISOU 1018 N ARG A 281 5219 6006 6489 895 -525 -580 N

ATOM 974 CD2 TYR A 274 -3.580 -71.616 -60.643 1.00 55.22 C ATOM 1019 CA ARG A 281 -2.451 -67.205 -72.066 1.00 41.03 C

ANISOU 974 CD2 TYR A 274 5817 6966 8198 -569 1288 -821 C ANISOU 1019 CA ARG A 281 4752 5356 5482 820 -618 -360 C

ATOM 975 C TYR A 274 -5.178 -67.233 -62.001 1.00 41.43 C ATOM 1020 CB ARG A 281 -3.716 -67.664 -72.783 1.00 33.20 C

ANISOU 975 C TYR A 274 3266 5659 6819 60 905 -859 C ANISOU 1020 CB ARG A 281 3729 4550 4335 888 -819 -278 C

ATOM 976 O TYR A 274 -4.122 -66.722 -62.405 1.00 35.34 O ATOM 1021 CG ARG A 281 -3.662 -69.087 -73.250 1.00 54.60 C

ANISOU 976 O TYR A 274 2653 4752 6023 181 767 -816 O ANISOU 1021 CG ARG A 281 6606 7383 6756 751 -981 -206 C

ATOM 977 N SERA 275 -6.204 -66.525 -61.578 1.00 36.49 N ATOM 1022 CD ARG A 281 -4.263 -69.236 -74.634 1.00 84.05 C

ANISOU 977 N SER A 275 2392 5179 6294 168 992 -885 N ANISOU 1022 CD ARG A 281 10451 11138 10347 955 -1184 -65 C

ATOM 978 CA SER A 275 -6.271 -65.073 -61.646 1.00 39.77 C ATOM 1023 NE ARG A 281 -4.000 -70.562 -75.185 1.00 96.97 N

ANISOU 978 CA SER A 275 2710 5599 6803 448 920 -870 C ANISOU 1023 NE ARG A 281 12281 12830 11735 866 -1361 -56 N

ATOM 979 CB SER A 275 -7.688 -64.597 -61.343 1.00 39.32 C ATOM 1024 CZ ARG A 281 -4.766 -71.627 -74.973 1.00104.06 C

ANISOU 979 CB SER A 275 2337 5746 6859 536 1040 -903 C ANISOU 1024 CZ ARG A 281 13075 13868 12593 678 -1580 -163 C

ATOM 980 OG SER A 275 -8.067 -64.994 -60.077 1.0040.50 O ATOM 1025 NHl ARG A 281 -4.438 -72.796 -75.510 1.00111.91 N

ANISOU 980 OG SER A 275 2529 5907 6952 459 1290 -953 O ANISOU 1025 NHl ARG A 281 14255 14839 13427 619 -1764 -188 N

ATOM 981 C SER A 275 -5.216 -64.398 -60.787 1.00 35.19 C ATOM 1026 NH2 ARG A 281 -5.857 -71.527 -74.226 1.00 99.41 N

ANISOU 981 C SER A 275 2403 4793 6174 609 948 -897 C ANISOU 1026 NH2 ARG A 281 12177 13434 12162 554 -1610 -246 N

ATOM 982 O SERA 275 -4.810 -63.313 -61.047 1.00 47.30 O ATOM 1027 C ARG A 281 -1.373 -66.849 -73.087 1.00 45.00 C

ANISOU 982 O SER A 275 3947 6225 7802 808 848 -882 O ANISOU 1027 C ARG A 281 5480 5578 6040 949 -522 -115 C

ATOM 983 N GLN A 276 -4.830 -65.075 -59.739 1.00 42.25 N ATOM 1028 O ARG A 281 -0.584 -67.700 -73.514 1.00 48.57 O

ANISOU 983 N GLN A 276 3514 5608 6932 530 1088 -942 N ANISOU 1028 O ARG A 281 6134 6038 6282 884 -523 -7 O





 ATOM 1299 CG GLN A 315 4.312 -74.862 -82.822 1.00 92.81 C ATOM 1344 -1.514 -81.762 -89.887 1.00120.53 C ANISOU 1299 CG GLN A 315 15444 7359 12459 1471 -1586 29 ANISOU 1344 CB SER A 321 18232 12090 15472 3001 -5595 51 C ATOM 1300 CD GLN A 315 3.692 -74.009 -83.911 1.00100.51 C ATOM 1345 OG SERA 321 -0.960 -82.971 -89.394 1.00110.50 O ANISOU 1300 CD GLN A 315 17125 7915 13148 1707 -1728 281 ANISOU 1345 OG SER A 321 16582 11082 14319 2792 -5451 -165 O ATOM 1301 OE1 GLN A 315 2.573 -74.252 -84.334 1.00104.15 ATOM 1346 c SER A 321 -3.379 -82.273 -88.325 1.00127.96 C ANISOU 1301 OE1 GLN A 315 17605 8249 13719 2135 -2186 407 ANISOU 1346 c SER A 321 17888 13424 17306 3077 -5524 -200 C ATOM 1302 NE2 GLN A 315 4.434 -73.016 -84.385 1.00100.46 ] ATOM 1347 0 SER A 321 -3.604 -81.510 -87.382 1.00125.70 O ANISOU 1302 NE2 GLN A 315 17708 7693 12771 1427 -1336 353 ANISOU 1347 0 SER A 321 17394 13052 17315 3145 -5290 -174 O ATOM 1303 C GLN A 315 2.566 -77.648 -82.250 1.00 92.39 C ATOM 1348 N SER A 322 -3.416 -83.597 -88.224 1.00127.79 N ANISOU 1303 C GLN A 315 13930 7932 13242 1924 -2368 -262 ANISOU 1348 N SER A 322 17502 13686 17368 2902 -5526 -403 N ATOM 1304 O GLN A 315 2.979 -77.990 -83.337 1.00 99.61 O ATOM 1349 CA SER A 322 -3.370 -84.265 -86.937 1.00125.23 C ANISOU 1304 O GLN A 315 15145 8925 13778 1857 -2492 -223 ANISOU 1349 CA SERA 322 16592 13562 17427 2736 -5193 -613 C ATOM 1305 N GLU A 316 1.380 -78.034 -81.796 1.00 90.84 N ATOM 1350 CB SER A 322 -4.329 -85.449 -86.871 1.00128.30 C ANISOU 1305 N GLU A 316 13264 7769 13483 2228 -2668 -305 N ANISOU 1350 CB SER A 322 16528 14228 17990 2634 -5236 -781 C ATOM 1306 CA GLU A 316 0.488 -78.789 -82.653 1.00 86.85 C ATOM 1351 OG SERA 322 -5.262 -85.264 -85.819 1.00130.27 O ANISOU 1306 CA GLU A 316 12586 7385 13027 2517 -3204 ■291 C ANISOU 1351 OG SER A 322 16328 14544 18623 2644 -5043 -836 O ATOM 1307 CB GLU A 316 -0.433 -79.685 -81.856 1.00 81.04 C ATOM 1352 C SER A 322 -1.928 -84.692 -86.697 1.00114.89 C ANISOU 1307 CB GLU A 316 11087 6995 12709 2531 -3240 459 C ANISOU 1352 C SER A 322 15414 12253 15984 2572 -4992 -687 C ATOM 1308 CG GLU A 316 0.226 -80.498 -80.781 1.00 76.25 C ATOM 1353 O SER A 322 -1.412 -85.622 -87.320 1.00114.32 O ANISOU 1308 CG GLU A 316 10098 6686 12187 2314 -3180 ■685 C ANISOU 1353 O SER A 322 15461 12308 15666 2456 -5089 -760 O ATOM 1309 CD GLU A 316 -0.679 -81.571 -80.240 1.00 81.39 C ATOM 1354 N PHE A 323 -1.299 -83.965 -85.788 1.00104.42 N ANISOU 1309 CD GLU A 316 10104 7675 13145 2186 -3040 ■844 C ANISOU 1354 N PHE A 323 14075 10778 14821 2565 -4693 -662 N ATOM 1310 OE1 GLU A 316 -1.681 -81.883 -80.893 1.00 82.49 O ATOM 1355 CA PHE A 323 0.123 -84.024 -85.526 1.00 92.32 C ANISOU 1310 OE1 GLU A 316 10041 7941 13360 2291 -3228 -829 O ANISOU 1355 CA PHE A 323 12725 9228 13124 2328 -4312 -707 C ATOM 1311 OE2 GLU A 316 -0.386 -82.111 -79.167 1.00 84.72 O ATOM 1356 CB PHE A 323 0.442 -82.860 -84.583 1.00 86.87 C ANISOU 1311 OE2 GLU A 316 10278 8213 13698 1952 -2720 -982 O ANISOU 1356 CB PHE A 323 12071 8324 12612 2307 -3944 -643 C ATOM 1312 C GLU A 316 -0.366 -77.791 -83.360 1.00 92.02 C ATOM 1357 CG PHE A 323 1.744 -82.973 -83.863 1.00 84.24 C ANISOU 1312 C GLU A 316 13622 7805 13535 2825 -3480 -54 C ANISOU 1357 CG PHE A 323 11684 8096 12228 1945 -3391 -759 C ATOM 1313 O GLU A 316 -1.096 -77.062 -82.733 1.00 95.16 O ATOM 1358 CD1 PHE A 323 2.919 -82.534 -84.453 1.00 81.08 C ANISOU 1313 O GLU A 316 13834 8162 14160 2954 -3383 8 O ANISOU 1358 CD1 PHE A 323 11794 7624 11388 1697 -3085 -687 C ATOM 1314 N PRO A 317 -0.289 -77.772 -84.674 1.00 99.97 N ATOM 1359 CE1 PHE A 323 4.123 -82.615 -83.774 1.00 67.68 C ANISOU 1314 N PRO A 317 15164 8694 14125 2909 -3774 81 N ANISOU 1359 CE1 PHE A 323 10004 6048 9665 1362 -2588 -796 C ATOM 1315 CA PRO A 317 -0.969 -76.740 -85.454 1.00110.29 C ATOM 1360 CZ PHE A 323 4.154 -83.130 -82.481 1.00 70.89 C ANISOU 1315 CA PRO A 317 16878 9797 15230 3149 -3965 312 C ANISOU 1360 CZ PHE A 323 9836 6632 10467 1283 -2411 -967 C ATOM 1316 CB PRO A 317 -0.519 -77.025 -86.886 1.00112.90 C ATOM 1361 CE2 PHE A 323 2.978 -83.558 -81.879 1.00 74.76 C ANISOU 1316 CB PRO A 317 17808 10049 15039 3138 -4246 416 C ANISOU 1361 CE2 PHE A 323 9862 7166 11377 1525 -2698 -1036 C ATOM 1317 CG PRO A 317 -0.242 -78.494 -86.899 1.00110.25 ATOM 1362 CD2 PHE A 323 1.786 -83.474 -82.569 1.00 78.37 C ANISOU 1317 CG PRO A 317 17070 10076 14746 2955 -4326 208 ANISOU 1362 CD2 PHE A 323 10384 7515 11878 1849 -3174 -938 C ATOM 1318 CD PRO A 317 0.342 -78.786 -85.534 1.00103.75 ATOM 1363 C PHE A 323 0.519 -85.375 -84.940 1.00 85.93 C ANISOU 1318 CD PRO A 317 15752 9415 14254 2693 -3853 4 ANISOU 1363 C PHE A 323 11443 8743 12464 2111 -4135 -952 C ATOM 1319 C PRO A 317 -2.477 -76.882 -85.353 1.00115.18 ATOM 1364 O PHE A 323 -0.255 -85.999 -84.218 1.00 94.92 O ANISOU 1319 C PRO A 317 16957 10648 16158 3381 -4236 303 ANISOU 1364 O PHE A 323 12062 10045 13958 2138 -4179 -1092 O ATOM 1320 O PRO A 317 -3.004 -77.992 -85.440 1.00114.75 O ATOM 1365 N SER A 324 1.712 -85.845 -85.280 1.00 67.43 N ANISOU 1320 O PRO A 317 16448 10917 16233 3357 -4463 159 O ANISOU 1365 N SER A 324 9311 6518 9791 1822 -3826 -1010 N ATOM 1321 N ALA A 318 -3.162 -75.762 -85.149 1.00119.53 N ATOM 1366 CA SER A 324 2.182 -87.103 -84.731 1.00 59.71 C ANISOU 1321 N ALA A 318 17573 11021 16821 3581 -4170 451 N ANISOU 1366 CA SERA 324 7925 5829 8933 1631 -3631 -1229 C ATOM 1322 CA ALA A 318 -4.611 -75.752 -85.183 1.00119.96 C ATOM 1367 CB SER A 324 2.670 -88.044 -85.824 1.00 57.13 C ANISOU 1322 CA ALA A 318 17214 11238 17127 3819 -4414 478 C ANISOU 1367 CB SER A 324 7854 5644 8210 1499 -3686 -1273 C ATOM 1323 CB ALA A 318 -5.144 -74.414 -84.712 1.00111.78 C ATOM 1368 OG SERA 324 2.801 -89.359 -85.318 1.00 61.93 O ANISOU 1323 CB ALA A 318 16268 9955 16250 4024 -4215 642 C ANISOU 1368 OG SER A 324 8032 6516 8984 1395 -3599 -1483 O ATOM 1324 C ALA A 318 -5.050 -76.031 -86.614 1.00132.46 C ATOM 1369 c SER A 324 3.291 -86.853 -83.732 1.00 68.42 C ANISOU 1324 C ALA A 318 19062 12866 18403 3957 -4900 570 C ANISOU 1369 c SER A 324 8901 6975 10118 1389 -3102 -1296 C ATOM 1325 O ALA A 318 -6.016 -76.756 -86.854 1.00138.36 O ATOM 1370 0 SER A 324 4.389 -86.437 -84.100 1.00 78.78 O ANISOU 1325 O ALA A 318 19398 13877 19296 4023 -5182 494 O ANISOU 1370 0 SER A 324 10574 8248 11112 1183 -2791 -1240 O ATOM 1326 N ASP A 319 -4.316 -75.458 -87.562 1.00139.08 N ATOM 1371 N LEU A 325 2.993 -87.103 -82.464 1.00 72.69 N ANISOU 1326 N ASP A 319 20628 13433 18783 3964 -4963 730 N ANISOU 1371 N LEU A 325 8932 7600 11087 1401 -3002 -1422 N ATOM 1327 CA ASP A 319 -4.604 -75.619 -88.981 1.00147.58 C ATOM 1372 CA LEU A 325 3.979 -86.960 -81.410 1.00 68.75 C ANISOU 1327 CA ASP A 319 22080 14508 19485 4067 -5395 834 C ANISOU 1372 CA LEU A 325 8262 7169 10691 1168 -2541 -1500 C ATOM 1328 CB ASP A 319 -3.747 -74.655 -89.808 1.00149.84 C ATOM 1373 CB LEU A 325 3.331 -87.207 -80.050 1.00 58.12 C ANISOU 1328 CB ASP A 319 23260 14420 19252 4051 -5315 1034 C ANISOU 1373 CB LEU A 325 6381 5868 9833 1235 -2527 -1626 C ATOM 1329 CG ASP A 319 -4.309 -74.412 -91.195 1.00157.47 C ATOM 1374 CG LEU A 325 4.100 -86.672 -78.850 1.00 58.26 C ANISOU 1329 CG ASP A 319 24644 15322 19867 4227 -5737 1190 C ANISOU 1374 CG LEU A 325 6273 5869 9994 1036 -2108 -1663 C ATOM 1330 OD2 ASP A 319 -3.516 -74.147 -92.124 1.00155.33 O ATOM 1375 CD1 LEU A 325 4.480 -85.235 -79.126 1.00 53.01 C ANISOU 1330 OD2 ASP A 319 25108 14841 19068 4118 -5734 1292 O ANISOU 1375 CD1 LEU A 325 6057 4951 9135 994 -1956 -1486 C ATOM 1331 OD1 ASP A 319 -5.547 -74.480 -91.357 1.00164.57 O ATOM 1376 CD2 LEU A 325 3.250 -86.769 -77.596 1.00 55.50 C ANISOU 1331 OD1 ASP A 319 25149 16373 21005 4457 -6050 1209 O ANISOU 1376 CD2 LEU A 325 5593 5558 9937 997 -2039 -1715 C ATOM 1332 C ASP A 319 -4.368 -77.052 -89.456 1.00152.05 C ATOM 1377 C LEU A 325 5.078 -87.981 -81.669 1.00 61.37 C ANISOU 1332 C ASP A 319 22482 15356 19934 3883 -5615 665 C ANISOU 1377 C LEU A 325 7308 6481 9528 935 -2312 -1615 C ATOM 1333 O ASP A 319 -3.304 -77.628 -89.216 1.00152.57 O ATOM 1378 O LEU A 325 6.270 -87.706 -81.527 1.00 57.75 O ANISOU 1333 O ASP A 319 22637 15443 19891 3648 -5418 560 O ANISOU 1378 O LEU A 325 6975 6065 8901 702 -1936 -1614 O ATOM 1334 N ASP A 320 -5.376 -77.619 -90.117 1.00153.32 N ATOM 1379 N SER A 326 4.675 -89.168 -82.055 1.00 57.01 N ANISOU 1334 N ASP A 320 22404 15724 20126 3988 -6005 641 N ANISOU 1379 N SER A 326 6597 6089 8974 1004 -2541 -1717 N ATOM 1335 CA ASP A 320 -5.254 -78.896 -90.823 1.00146.21 C ATOM 1380 CA SER A 326 5.605 -90.218 -82.325 1.00 58.67 C ANISOU 1335 CA ASP A 320 21461 15053 19040 3825 -6248 510 C ANISOU 1380 CA SERA 326 6789 6521 8981 831 -2353 -1831 C ATOM 1336 CB ASP A 320 -4.260 -78.773 -91.990 1.00147.85 C ATOM 1381 CB SER A 326 4.863 -91.496 -82.546 1.00 63.95 C ANISOU 1336 CB ASP A 320 22484 15053 18638 3729 -6334 629 C ANISOU 1381 CB SER A 326 7302 7311 9685 946 -2675 -1937 C ATOM 1337 CG ASP A 320 -4.875 -78.151 -93.230 1.00152.59 C ATOM 1382 OG SERA 326 4.079 -91.363 -83.677 1.00 78.93 O ANISOU 1337 CG ASP A 320 23549 15507 18922 3915 -6686 819 C ANISOU 1382 OG SER A 326 8856 9234 11900 999 -2516 -1957 O ATOM 1338 OD2 ASP A 320 -4.107 -77.783 -94.143 1.00153.12 O ATOM 1383 C SER A 326 6.537 -89.917 -83.473 1.00 59.11 c ANISOU 1338 OD2 ASP A 320 24366 15345 18468 3840 -6690 945 O ANISOU 1383 C SER A 326 7350 6533 8578 681 -2172 -1734 c ATOM 1339 OD1 ASP A 320 -6.118 -78.047 -93.300 1.00156.73 O ATOM 1384 O SER A 326 7.683 -90.242 -83.390 1.00 55.11 o ANISOU 1339 OD1 ASP A 320 23701 16144 19704 4122 -6940 843 O ANISOU 1384 O SER A 326 6830 6163 7947 473 -1805 -1796 o ATOM 1340 C ASP A 320 -4.759 -79.929 -89.813 1.00132.77 C ATOM 1385 N GLN A 327 6.068 -89.296 -84.541 1.00 61.56 N ANISOU 1340 C ASP A 320 19246 13616 17583 3584 -6042 259 C ANISOU 1385 N GLN A 327 8105 6652 8635 789 -2430 -1585 N ATOM 1341 O ASP A 320 -5.434 -80.246 -88.830 1.00123.63 O ATOM 1386 CA GLN A 327 6.942 -88.928 -85.642 1.00 58.07 c ANISOU 1341 O ASP A 320 17438 12703 16831 3565 -5998 107 O ANISOU 1386 CA GLN A 327 8208 6130 7727 641 -2262 -1489 c ATOM 1342 N SER A 321 -3.571 -80.434 -90.063 1.00130.82 N ATOM 1387 CB GLN A 327 6.142 -88.368 -86.818 1.00 60.68 c ANISOU 1342 N SER A 321 19344 13304 17059 3391 -5889 227 N ANISOU 1387 CB GLN A 327 9025 6236 7793 810 -2653 -1323 c ATOM 1343 CA SER A 321 -3.034 -81.747 -89.714 1.00128.83 C ATOM 1388 CG GLN A 327 5.491 -89.452 -87.653 1.00 56.58 c ANISOU 1343 CA SERA 321 18757 13306 16887 3161 -5789 8 C ANISOU 1388 8536 5816 7147 904 -3015 -1380 c ATOM 1389 CD GLN A 327 6488 -90.527 -88.072 1.00 61.98 C ATOM 1434 CE1 HIS A 332 12.730 -83.012 -82.485 1.00 67.36 C ANISOU 1389 CD GLN A 327 9272 6687 7591 691 -2731 -1510 C ANISOU 1434 CE1 HIS A 332 9987 6931 8677 -748 112 -1295 c ATOM 1390 OE1 GLN A 327 7.400 -90.268 -88.859 1.00 74.76 O ATOM 1435 NE2 HIS A 332 13.652 -82.567 -81.662 1.00 62.85 N ANISOU 1390 OE1 GLN A 327 11335 8241 8827 525 -2482 -1455 O ANISOU 1435 NE2 HIS A 332 9338 6416 8125 -1045 494 -1339 N ATOM 1391 NE2 GLN A 327 6.327 -91.736 -87.533 1.00 55.10 N ATOM 1436 CD2 HIS A 332 14.397 -83.620 -81.210 1.00 54.31 C ANISOU 1391 NE2 GLN A 327 7954 6036 6947 696 -2742 -1686 N ANISOU 1436 CD2 HIS A 332 7810 5682 7143 -1203 685 -1495 c ATOM 1392 C GLN A 327 7.970 -87.917 -85.169 1.00 56.30 C ATOM 1437 C HIS A 332 15.620 -87.942 -82.617 1.00 65.45 c ANISOU 1392 C GLN A 327 8105 5832 7456 443 -1833 -1435 C ANISOU 1437 C HIS A 332 8431 7973 8463 -1092 724 -1869 c ATOM 1393 O GLN A 327 9.128 -87.939 -85.582 1.00 56.11 O ATOM 1438 O HIS A 332 16.810 -87.905 -82.478 1.00 67.77 o ANISOU 1393 O GLN A 327 8297 5865 7156 217 -1491 -1450 O ANISOU 1438 O HIS A 332 8631 8437 8682 -1335 1093 -1928 o ATOM 1394 N GLU A 328 7.530 -87.042 -84.276 1.00 47.72 N ATOM 1439 N LEU A 333 14.897 -89.026 -82.413 1.00 74.14 N ANISOU 1394 N GLU A 328 6865 4618 6649 519 -1841 -1384 N ANISOU 1439 N LEU A 333 9248 9171 9751 -863 453 -1938 N ATOM 1395 CA GLU A 328 8.375 -85.995 -83.731 1.00 65.69 C ATOM 1440 CA LEU A 333 15.481 -90.283 -81.956 1.00 72.04 c ANISOU 1395 CA GLU A 328 9256 6801 8903 323 -1458 -1334 C ANISOU 1440 CA LEU A 333 8543 9204 9626 -862 573 -2082 c ATOM 1396 CB GLU A 328 7.537 -85.047 -82.880 1.00 53.31 C ATOM 1441 CB LEU A 333 14.388 -91.334 -81.756 1.00 77.23 c ANISOU 1396 CB GLU A 328 7575 5035 7646 478 -1566 -1262 C ANISOU 1441 CB LEU A 333 8982 9884 10476 -595 220 -2142 c ATOM 1397 CG GLU A 328 8.225 -83.757 -82.563 1.00 62.79 C ATOM 1442 CG LEU A 333 14.047 -91.758 -80.332 1.00 75.86 c ANISOU 1397 CG GLU A 328 9056 6054 8749 296 -1228 -1172 C ANISOU 1442 CG LEU A 333 8299 9832 10694 -523 144 -2229 c ATOM 1398 CD GLU A 328 8.302 -82.845 -83.767 1.00 85.08 C ATOM 1443 CD1 LEU A 333 13.263 -93.058 -80.359 1.00 68.32 c ANISOU 1398 CD GLU A 328 12553 8611 11163 310 -1268 -991 C ANISOU 1443 CD1 LEU A 333 7162 8941 9854 -309 -108 -2321 c ATOM 1399 OE1 GLU A 328 9.137 -81.911 -83.750 1.00 85.59 O ATOM 1444 CD2 LEU A 333 15.314 -91.918 -79.519 1.00 78.69 c ANISOU 1399 OE1 GLU A 328 12936 8549 11035 83 -921 -934 O ANISOU 1444 CD2 LEU A 333 8326 10434 11141 -712 488 -2305 c ATOM 1400 OE2 GLU A 328 7.525 -83.063 -84.728 1.00 95.00 O ATOM 1445 C LEU A 333 16.506 -90.842 -82.930 1.00 71.32 c ANISOU 1400 OE2 GLU A 328 14035 9783 12278 535 -1648 -909 O ANISOU 1445 C LEU A 333 8613 9236 9251 -976 845 -2126 c ATOM 1401 C GLU A 328 9.492 -86.593 -82.879 1.00 63.08 C ATOM 1446 O LEU A 333 17.533 -91.392 -82.531 1.00 72.07 o ANISOU 1401 C GLU A 328 8547 6737 8684 75 -1064 -1491 C ANISOU 1446 O LEU A 333 8388 9580 9415 -1085 1126 -2222 o ATOM 1402 O GLU A 328 10.668 -86.241 -83.013 1.00 59.40 O ATOM 1447 N ARG A 334 16.208 -90.712 -84.215 1.00 68.75 N ANISOU 1402 O GLU A 328 8252 6311 8006 -181 -695 -1490 O ANISOU 1447 N ARG A 334 8787 8728 8605 -941 756 -2054 N ATOM 1403 N VAL A 329 9.108 -87.498 -81.990 1.00 54.87 N ATOM 1448 CA ARG A 334 16.986 -91.378 -85.244 1.00 64.04 c ANISOU 1403 N VAL A 329 6988 5879 7981 153 -1150 -1627 N ANISOU 1448 CA ARG A 334 8394 8211 7727 -1017 984 -2103 c ATOM 1404 CA VAL A 329 10.066 -88.135 -81.111 1.00 53.12 C ATOM 1449 CB ARG A 334 16.163 -91.522 -86.524 1.00 49.46 c ANISOU 1404 CA VAL A 329 6382 5912 7889 -38 -833 -1769 C ANISOU 1449 CB ARG A 334 7065 6146 5580 -891 710 -2031 c ATOM 1405 CB VAL A 329 9.380 -89.004 -80.063 1.00 54.00 C ATOM 1450 CG ARG A 334 15.062 -92.561 -86.366 1.00 54.21 c ANISOU 1405 CB VAL A 329 5972 6153 8391 90 -981 -1900 C ANISOU 1450 CG ARG A 334 7465 6781 6349 -634 316 -2083 c ATOM 1406 CGI VAL A 329 10.420 -89.658 -79.161 1.00 32.72 C ATOM 1451 CD ARG A 334 13.975 -92.462 -87.424 1.00 57.75 c ANISOU 1406 CGI VAL A 329 2914 3716 5803 -96 -668 -2032 C ANISOU 1451 CD ARG A 334 8382 7000 6560 -498 -73 -1991 c ATOM 1407 CG2 VAL A 329 8.426 -88.164 -79.248 1.00 35.27 C ATOM 1452 NE ARG A 334 13.199 -93.699 -87.494 1.00 56.49 N ANISOU 1407 CG2 VAL A 329 3498 3587 6317 213 -1116 -1850 C ANISOU 1452 NE ARG A 334 8054 6921 6489 -320 -356 -2080 N ATOM 1408 C VAL A 329 11.014 -88.986 -81.930 1.00 52.84 C ATOM 1453 CZ ARG A 334 11.980 -93.808 -88.014 1.00 59.56 c ANISOU 1408 C VAL A 329 6447 6060 7568 -162 -663 -1829 C ANISOU 1453 CZ ARG A 334 8637 7174 6819 -158 -802 -2031 c ATOM 1409 O VAL A 329 12.223 -89.004 -81.694 1.00 62.39 O ATOM 1454 NHl ARG A 334 11.366 -92.741 -88.513 1.00 65.55 N ANISOU 1409 O VAL A 329 7584 7419 8702 -386 -300 -1878 O ANISOU 1454 NHl ARG A 334 9767 7703 7438 -114 -1041 -1878 N ATOM 1410 N LEU A 330 10.478 -89.670 -82.909 1.00 49.00 N ATOM 1455 ΝΉ2 ARG A 334 11.369 -94.987 -88.030 1.00 54.39 N ANISOU 1410 N LEU A 330 6132 5563 6924 -19 -925 -1828 N ANISOU 1455 ΝΉ2 ARG A 334 7806 6614 6245 -40 -1014 -2137 N ATOM 1411 CA LEU A 330 11.275 -90.514 -83.735 1.00 54.01 C ATOM 1456 C ARG A 334 18.330 -90.702 -85.487 1.00 85.34 C ANISOU 1411 CA LEU A 330 6893 6344 7284 -114 -771 -1891 C ANISOU 1456 C ARG A 334 11215 10962 10248 -1313 1449 -2104 ATOM 1412 CB LEU A 330 10.408 -91.383 -84.626 1.00 54.45 C ATOM 1457 O ARG A 334 18.599 -90.201 -86.578 1.00 87.32 O ANISOU 1412 CB LEU A 330 7089 6373 7225 66 -1136 -1905 C ANISOU 1457 O ARG A 334 11979 11049 10152 -1431 1581 -2042 O ATOM 1413 CG LEU A 330 9.927 -92.679 -84.014 1.00 47.37 C ATOM 1458 N GLN A 335 19.149 -90.681 -84.433 1.00 99.41 N ANISOU 1413 CG LEU A 330 5736 5657 6604 180 -1278 -2058 C ANISOU 1458 N GLN A 335 12525 12975 12272 -1441 1688 -2178 N ATOM 1414 CD1 LEU A 330 8.817 -93.282 -84.823 1.00 40.73 C ATOM 1459 CA GLN A 335 20.533 -90.204 -84.463 1.00101.72 C ANISOU 1414 CD1 LEU A 330 5047 4751 5676 351 -1704 -2058 C ANISOU 1459 CA GLN A 335 12776 13402 12471 -1740 2148 -2216 C ATOM 1415 CD2 LEU A 330 11.042 -93.658 -83.827 1.00 37.71 C ATOM 1460 CB GLN A 335 20.625 -88.732 -84.877 1.00 96.70 C ANISOU 1415 CD2 LEU A 330 4344 4664 5321 48 -930 -2184 C ANISOU 1460 CB GLN A 335 12614 12522 11606 -1959 2269 -2109 C ATOM 1416 C LEU A 330 12.286 -89.772 -84.546 1.00 60.61 C ATOM 1461 CG GLN A 335 19.533 -87.844 -84.316 1.00 92.69 C ANISOU 1416 C LEU A 330 8188 7093 7749 -318 -478 -1805 C ANISOU 1461 CG GLN A 335 12220 11781 11215 -1861 1949 -1999 C ATOM 1417 O LEU A 330 13.396 -90.220 -84.696 1.00 57.78 O ATOM 1462 CD GLN A 335 18.812 -87.082 -85.410 1.00 97.37 C ANISOU 1417 O LEU A 330 7807 6896 7251 -494 -140 -1877 O ANISOU 1462 CD GLN A 335 13490 12016 11489 -1807 1783 -1858 C ATOM 1418 N ARG A 331 11.901 -88.630 -85.074 1.00 60.96 N ATOM 1463 OE1 GLN A 335 18.806 -85.853 -85.425 1.00 97.60 O ANISOU 1418 N ARG A 331 8657 6870 7636 -289 -600 -1651 N ANISOU 1463 OE1 GLN A 335 13843 11834 11405 -1946 1862 -1764 ( ATOM 1419 CA ARG A 331 12.796 -87.887 -85.913 1.00 56.55 C ATOM 1464 NE2 GLN A 335 18.211 -87.812 -86.346 1.00 99.42 N ANISOU 1419 CA ARG A 331 8602 6178 6708 -492 -323 -1561 C ANISOU 1464 NE2 GLN A 335 13991 12199 11584 -1609 1552 -1840 ] ATOM 1420 CB ARG A 331 12.078 -86.673 -86.468 1.00 67.64 C ATOM 1465 C GLN A 335 21.198 -90.404 -83.104 1.00101.48 C ANISOU 1420 CB ARG A 331 10456 7250 7993 -389 -540 -1379 C ANISOU 1465 C GLN A 335 12117 13664 12776 -1815 2281 -2304 C ATOM 1421 CG ARG A 331 12.956 -85.480 -86.800 1.00 81.49 C ATOM 1466 O GLN A 335 21.642 -91.502 -82.776 1.00100.12 O ANISOU 1421 CG ARG A 331 12809 8814 9338 -599 -263 -1275 C ANISOU 1466 O GLN A 335 11547 13741 12754 -1722 2346 -2404 O ATOM 1422 CD ARG A 331 12.123 -84.291 -87.225 1.00 85.89 C TER 1467 GLN A 335

ANISOU 1422 CD ARG A 331 13751 9036 9848 -489 -434 -1096 C HETATM 1468 OAD DRG C 1 7.647 -76.692 -62.085 1.0044.74 O ATOM 1423 NE ARG A 331 12.252 -83.133 -86.353 1.00 86.24 N HETATM 1469 CAQ DRG C 1 8.003 -77.711 -61.497 1.00 55.27 C ANISOU 1423 NE ARG A 331 13631 9046 10091 -641 -151 -1097 N HETATM 1470 CAS DRG C 1 7.089 -78.705 -61.199 1.00 51.55 C ATOM 1424 CZ ARG A 331 13.405 -82.620 -85.942 1.00 88.99 C HETATM 1471 CAJ DRG C 1 5.760 -78.535 -61.568 1.00 51.37 C ANISOU 1424 CZ ARG A 331 14228 9350 10233 -955 286 -1091 C HETATM 1472 CAH DRG C 1 4.840 -79.541 -61.279 1.00 56.00 C ATOM 1425 NH1 ARG A 331 14.552 -83.174 -86.290 1.00 95.44 N HETATM 1473 CAN DRG C 1 5.237 -80.711 -60.627 1.0046.44 C ANISOU 1425 NH1 ARG A 331 15459 10150 10655 -1139 505 -1087 N HETATM 1474 CAA DRG C 1 4.300 -81.703 -60.347 1.00 26.68 C ATOM 1426 NH2 ARG A 331 13.409 -81.554 -85.160 1.00 77.36 N HETATM 1475 CAO DRG C 1 6.574 -80.882 -60.258 1.0045.72 C ANISOU 1426 NH2 ARG A 331 12601 7849 8944 -1105 518 -1099 N HETATM 1476 CAB DRG C 1 6.990 -82.043 -59.604 1.00 30.41 C ATOM 1427 C ARG A 331 13.998 -87.503 -85.080 1.00 69.23 C HETATM 1477 CAT DRG C 1 7.483 -79.863 -60.537 1.0043.76 C ANISOU 1427 C ARG A 331 9979 7930 8395 -768 147 -1628 C HETATM 1478 OAL DRG C 1 8.781 -80.059 -60.194 1.00 36.28 O ATOM 1428 O ARG A 331 15.111 -87.606 -85.529 1.00 76.31 O HETATM 1479 CAU DRG C 1 9.705 -79.109 -60.509 1.0047.85 C ANISOU 1428 O ARG A 331 11007 8924 9062 -987 497 -1671 O HETATM 1480 CAR DRG C 1 9.328 -77.933 -61.155 1.00 57.72 C ATOM 1429 N HIS A 332 13.775 -87.057 -83.857 1.00 66.23 N HETATM 1481 CAI DRG C 1 10.309 -76.990 -61.463 1.00 52.34 C ANISOU 1429 N HIS A 332 9246 7572 8346 -766 157 -1643 N HETATM 1482 CAF DRG C 1 11.633 -77.232 -61.107 1.00 41.69 C ATOM 1430 CA HIS A 332 14.851 -86.724 -82.964 1.00 59.31 C HETATM 1483 CAG DRG C 1 11.999 -78.407 -60.453 1.00 34.93 C ANISOU 1430 CA HIS A 332 8107 6854 7574 -1034 553 -1712 C HETATM 1484 CAP DRG C 1 11.022 -79.346 -60.145 1.00 47.31 C ATOM 1431 CB HIS A 332 14.317 -86.150 -81.685 1.0042.49 C HETATM 1485 CAK DRG C 1 11.361 -80.525 -59.495 1.00 48.85 C ANISOU 1431 CB HIS A 332 5715 4657 5772 -1008 490 -1699 C HETATM 1486 CAM DRG C 1 11.257 -81.740 -60.416 1.00 49.85 C ATOM 1432 CG HIS A 332 13.906 -84.728 -81.793 1.00 60.89 C HETATM 1487 OAE DRG C 1 10.890 -81.531 -61.601 1.00 37.91 O ANISOU 1432 CG HIS A 332 8476 6649 8008 -991 431 -1547 C HETATM 1488 OAC DRG C 11.567 -82.840 -59.898 1.0044.52 O ATOM 1433 NDl HIS A 332 12.862 -84.315 -82.580 1.00 70.24 N ATOM 1490 N SER B 154 8.907 -62.145 -63.562 1.00 35.71 N ANISOU 1433 NDl HIS A 332 9994 7582 9113 -727 74 -1425 N ANISOU 1490 N SER B 154 4521 4617 4430 -347 455 -551 N

 ATOM 1581 CB ILE B 165 2.130 -75.866 -59.428 1.00 33.68 ATOM 1626 CD1 LEU B 170 3.155 -81.663 -56.726 1.00 84.69 C ANISOU 1581 CB ILE B 165 4246 4795 3757 -1651 1063 458 ANISOU 1626 CD1 LEU B 170 10993 10585 10602 -1901 1258 630 C ATOM 1582 CGI ILE B 165 1.361 -74.551 -59.560 1.00 36.68 ATOM 1627 CD2 LEU B 170 0.892 -82.658 -57.052 1.00 86.63 C ANISOU 1582 CGI ILE B 165 4490 5446 4000 -1550 974 530 ANISOU 1627 CD2 LEU B 170 11177 11156 10583 -2332 1163 944 C ATOM 1583 CD1 ILE B 165 -0.100 -74.644 -59.088 1.00 38.43 ATOM 1628 C LEU B 170 1.250 -83.025 -52.387 1.00 65.89 C ANISOU 1583 CD1 ILE B 165 4561 5989 4052 -1588 906 763 ANISOU 1628 C LEU B 170 8189 8760 8085 -1573 1082 1282 C ATOM 1584 CG2 ILE B 165 1.545 -76.924 -60.351 1.00 35.04 ATOM 1629 O LEU B 170 0.874 -84.167 -52.118 1.00 67.30 O ANISOU 1584 CG2 ILE B 165 4518 4928 3867 -2011 1099 494 ANISOU 1629 O LEU B 170 8396 8905 8268 -1740 1079 1401 O ATOM 1585 C ILE B 165 2.932 -77.670 -57.892 1.00 49.39 ATOM 1630 N ILE B 171 1.943 -82.270 -51.544 1.00 56.51 N ANISOU 1585 C ILE B 165 6302 6530 5936 -1568 1137 488 ANISOU 1630 N ILE B 171 6938 7574 6958 -1258 1074 1224 N ATOM 1586 O ILE B 165 2.366 -78.759 -58.002 1.00 63.30 ATOM 1631 CA ILE B 171 2.448 -82.770 -50.275 1.00 57.34 C ANISOU 1586 O ILE B 165 8107 8285 7660 -1787 1154 577 ANISOU 1631 CA ILE B 171 7017 7613 7156 -1083 1072 1276 C ATOM 1587 N GLY B 166 4.240 -77.569 -57.736 1.00 45.47 ATOM 1632 CB ILE B 171 3.904 -82.277 -50.027 1.00 60.02 c ANISOU 1587 N GLY B 166 5876 5793 5606 -1412 1189 333 ANISOU 1632 CB ILE B 171 7421 7715 7670 -847 1106 1085 c ATOM 1588 CA GLY B 166 5.113 -78.712 -57.832 1.0040.49 ATOM 1633 CGI ILE B 171 4.906 -83.417 -50.235 1.00 58.39 c ANISOU 1588 CA GLY B 166 5395 4862 5128 -1509 1287 235 ANISOU 1633 CGI ILE B 171 7372 7154 7660 -951 1184 987 c ATOM 1589 C GLY B 166 5.567 -79.380 -56.570 1.00 50.71 ATOM 1634 CD1 ILE B 171 5.310 -84.128 -48.938 1.00 54.50 c ANISOU 1589 C GLY B 166 6666 6068 6533 -1347 1295 286 ANISOU 1634 CD1 ILE B 171 6850 6595 7261 -817 1174 1075 c ATOM 1590 O GLY B 166 6.226 -80.367 -56.617 1.00 53.81 ATOM 1635 CG2 ILE B 171 4.057 -81.657 -48.630 1.00 55.8 c ANISOU 1590 O GLY B 166 7177 6204 7066 -1401 1376 214 ANISOU 1635 CG2 ILE B 171 6774 7332 7127 -528 1048 1152 c ATOM 1591 N TYR B 167 5.229 -78.815 -55.437 1.00 49.00 ATOM 1636 C ILE B 171 1.529 -82.406 -49.098 1.00 54.34 c ANISOU 1591 N TYR B 167 6301 6062 6254 -1143 1212 413 ANISOU 1636 C ILE B 171 6449 7570 6628 -916 1000 1483 c ATOM 1592 CA TYR B 167 5.491 -79.458 -54.180 1.00 43.43 ATOM 1637 O ILE B 171 1.309 -83.212 -48.187 1.00 62.23 o ANISOU 1592 CA TYR B 167 5566 5301 5635 -995 1209 481 ANISOU 1637 O ILE B 171 7406 8607 7633 -913 987 1625 o ATOM 1593 CB TYR B 167 6.755 -78.908 -53.568 1.00 33.03 ATOM 1638 N LEU B 172 0.985 -81.194 -49.124 1.00 40.73 N ANISOU 1593 CB TYR B 167 4253 3822 4473 -731 1215 361 ANISOU 1638 N LEU B 172 4614 6093 4769 -775 956 1503 N ATOM 1594 CG TYR B 167 7.127 -79.517 -52.263 1.00 49.16 ATOM 1639 CA LEU B 172 0.141 -80.713 -48.030 1.00 49.61 c ANISOU 1594 CG TYR B 167 6261 5816 6603 -571 1202 437 ANISOU 1639 CA LEU B 172 5562 7547 5741 -579 899 1685 c ATOM 1595 CD1 TYR B 167 7.430 -80.839 -52.161 1.0040.45 ATOM 1640 CB LEU B 172 -0.139 -79.212 -48.149 1.0048.51 c ANISOU 1595 CD1 TYR B 167 5246 4514 5609 -694 1270 450 ANISOU 1640 CB LEU B 172 5340 7603 5487 -373 860 1644 c ATOM 1596 CE1 TYR B 167 7.777 -81.386 -50.966 1.00 36.31 ATOM 1641 CG LEU B 172 1.020 -78.271 -47.828 1.00 41.26 c ANISOU 1596 CE1 TYR B 167 4686 3945 5165 -555 1255 527 ANISOU 1641 CG LEU B 172 4478 6529 4668 -95 851 1456 c ATOM 1597 CZ TYR B 167 7.827 -80.621 -49.875 1.00 39.10 ATOM 1642 CD1 LEU I ! 172 0.544 -76.843 -47.895 1.00 39.83 c ANISOU 1597 CZ TYR B 167 4921 4456 5479 -290 1171 588 ANISOU 1642 CD1 LEU B 172 4214 6569 4351 95 800 1448 c ATOM 1598 OH TYR B 167 8.176 -81.142 -48.687 1.00 45.50 ATOM 1643 CD2 LEU I ! 172 1.584 -78.564 -46.447 1.00 48.72 c ANISOU 1598 OH TYR B 167 5700 5226 6363 -157 1152 669 ANISOU 1643 CD2 LEU B 172 5407 7428 5674 122 838 1491 c ATOM 1599 CE2 TYR B 167 7.531 -79.306 -49.944 1.00 32.94 ATOM 1644 C LEU ! 172 -1.170 -81.477 -47.787 1.00 63.57 c ANISOU 1599 CE2 TYR B 167 4064 3867 4584 -157 1104 568 ANISOU 1644 C LEU B 172 7220 9565 7369 -760 875 1939 c ATOM 1600 CD2 TYR B 167 7.189 -78.756 -51.134 1.00 32.64 ATOM 1645 O LEU B 172 -1.561 -81.651 -46.625 1.00 68.56 o ANISOU 1600 CD2 TYR B 167 4056 3871 4476 -297 1119 496 ANISOU 1645 O LEU B 172 7739 10374 7937 -620 850 2098 o ATOM 1601 C TYR B 167 4.329 -79.357 -53.204 1.00 48.10 ATOM 1646 N PRO B 173 -1.871 -81.903 -48.864 1.00 58.72 N ANISOU 1601 C TYR B 167 6003 6192 6081 -904 1126 685 ANISOU 1646 N PRO B 173 6633 8980 6700 -1070 876 1987 N ATOM 1602 O TYR B 167 3.822 -80.344 -52.760 1.00 55.34 ATOM 1647 CA PRO B 173 -3.172 -82.549 -48.642 1.00 64.63 c ANISOU 1602 O TYR B 167 6907 7143 6975 -1005 1127 817 ANISOU 1647 CA PRO B 173 7259 9991 7306 -1249 839 2250 c ATOM 1603 N LEU B 168 3.946 -78.152 -52.833 1.00 42.29 ATOM 1648 CB PRO B 173 -3.577 -83.004 -50.042 1.00 57.76 c ANISOU 1603 N LEU B 168 5151 5676 5241 -711 1053 716 ANISOU 1648 CB PRO B 173 6485 9044 6420 -1611 841 2230 c ATOM 1604 CA LEU B 168 3.056 -77.956 -51.722 1.00 42.28 ATOM 1649 CG PRO I ! 173 -2.985 -81.972 -50.927 1.00 58.83 c ANISOU 1604 CA LEU B 168 5000 5958 5107 -559 983 898 ANISOU 1649 CG PRO B 173 6693 9073 6589 -1535 864 2012 c ATOM 1605 CB LEU B 168 2.952 -76.480 -51.413 1.00 33.21 ATOM 1650 CD PRO I ! 173 -1.650 -81.652 -50.301 1.00 46.16 c ANISOU 1605 CB LEU B 168 3762 4984 3874 -297 912 879 ANISOU 1650 CD PRO B 173 5160 7240 5139 -1258 901 1829 c ATOM 1606 CG LEU B 168 4.163 -75.971 -50.672 1.00 35.57 ATOM 1651 C PRO ! 173 -3.153 -83.747 -47.692 1.00 64.28 c ANISOU 1606 CG LEU B 168 4093 5120 4302 -25 894 761 ANISOU 1651 C PRO B 173 7210 9898 7313 -1295 837 2386 c ATOM 1607 CD1 LEU I ! 168 4.005 -74.554 -50.241 1.00 37.53 ATOM 1652 O PRO B 173 -4.082 -83.891 -46.896 1.00 65.21 o ANISOU 1607 CD1 LEU B 168 4264 5551 4446 234 809 759 ANISOU 1652 O PRO B 173 7167 10307 7304 -1261 801 2619 o ATOM 1608 CD2 LEU I ! 168 4.462 -76.820 -49.480 1.00 34.97 ATOM 1653 N GLU B 174 -2.124 -84.586 -47.774 1.00 62.33 N ANISOU 1608 CD2 LEU B 168 4002 4993 4291 66 901 842 ANISOU 1653 N GLU B 174 7133 9300 7250 -1367 878 2253 N ATOM 1609 C LEU I ! 168 1.672 -78.546 -51.914 1.00 53.61 ATOM 1654 CA GLU B 174 -2.043 -85.763 -46.914 1.00 51.04 c ANISOU 1609 C LEU B 168 6364 7620 6387 -778 968 1090 ANISOU 1654 CA GLU B 174 5714 7794 5885 -1420 873 2377 c ATOM 1610 O LEU ] i 168 1.157 -79.205 -51.059 1.00 36.39 ATOM 1655 CB GLU B 174 -1.623 -86.998 -47.708 1.00 52.82 c ANISOU 1610 O LEU B 168 4109 5556 4162 -762 951 1252 ANISOU 1655 CB GLU B 174 6138 7689 6243 -1725 904 2303 c ATOM 1611 N ARG 3 169 1.100 -78.342 -53.076 1.00 50.76 ATOM 1656 CG GLU B 174 -2.767 -87.699 -48.405 1.00 75.76 c ANISOU 1611 N ARG I B 169 6019 7326 5940 -990 969 1084 ANISOU 1656 CG GLU B 174 9040 10710 9034 -2079 862 2467 c ATOM 1612 CA ARG I ! 169 -0.270 -78.792 -53.279 1.00 60.81 ATOM 1657 CD GLU B 174 -3.715 -88.372 -47.427 1.00 99.46 c ANISOU 1612 CA ARG B 169 7208 8842 7055 -1200 938 1282 ANISOU 1657 CD GLU B 174 11912 13921 11955 -2084 785 2694 ATOM 1613 CB ARG B 169 -0.957 -78.010 -54.392 1.00 51.65 ATOM 1658 OE1 GLU B 174 -4.920 -88.043 -47.447 1.00107.31 ANISOU 1613 CB ARG B 169 6019 7832 5774 -1325 909 1281 ANISOU 1658 OE1 GLU B 174 12772 15198 12804 -2075 702 2784 ATOM 1614 CG ARG I i 169 -0.830 -78.591 -55.776 1.00 54.22 ATOM 1659 OE2 GLU B 174 -3.253 -89.229 -46.643 1.00109.14 ANISOU 1614 CG ARG B 169 6497 7975 6131 -1654 952 1185 ANISOU 1659 OE2 GLU B 174 13172 15018 13278 -2084 799 2766 ATOM 1615 CD ARG I i 169 -1.611 -77.701 -56.714 1.00 60.70 ATOM 1660 C GLU B 174 -1.098 -85.588 -45.730 1.00 49.22 C ANISOU 1615 CD ARG B 169 7257 8994 6813 -1746 908 1215 ANISOU 1660 C GLU B 174 5473 7471 5756 -1110 886 2318 c ATOM 1616 NE ARG I i 169 -1.643 -78.152 -58.097 1.00 74.02 ATOM 1661 O GLU B 174 -0.711 -86.567 -45.100 1.00 52.18 o ANISOU 1616 NE ARG B 169 9082 10549 8492 -2073 936 1138 ANISOU 1661 O GLU B 174 5895 7699 6233 -1140 892 2369 o ATOM 1617 CZ ARG I i 169 -2.516 -77.696 -58.988 1.00 70.95 ATOM 1662 N LEU B 175 -0.721 -84.351 -45.428 1.00 42.59 N ANISOU 1617 CZ ARG B 169 8653 10322 7983 -2209 878 1188 ANISOU 1662 N LEU B 175 4580 6710 4891 -817 883 2215 N ATOM 1618 NHl ARG B 169 -3.412 -76.797 -58.611 1.00 71.31 ATOM 1663 CA LEU B 175 0.287 -84.119 -44.400 1.00 51.79 c ANISOU 1618 NHl ARG B 169 8517 10667 7909 -2054 801 1323 ANISOU 1663 CA LEU B 175 5759 7759 6160 -532 887 2136 c ATOM 1619 NH2 ARG B 169 -2.502 -78.136 -60.241 1.00 62.31 ATOM 1664 CB LEU B 175 0.852 -82.698 -44.468 1.00 56.18 c ANISOU 1619 NH2 ARG B 169 7707 9053 6913 -2413 866 1069 N ANISOU 1664 CB LEU B 175 6312 8324 6711 -267 879 1966 c ATOM 1620 C ARG B 169 -0.345 -80.302 -53.518 1.00 66.92 ATOM 1665 CG LEU B 175 2.121 -82.507 -43.635 1.00 51.60 c ANISOU 1620 C ARG B 169 8085 9460 7882 -1486 977 1330 ANISOU 1665 CG LEU B 175 5787 7543 6274 -16 879 1845 c ATOM 1621 O ARG I 3 169 -1.426 -80.881 -53.657 1.00 71.65 O ATOM 1666 CD1 LEU I ! 175 3.278 -83.296 -44.236 1.00 48.68 c ANISOU 1621 O ARG B 169 8630 10230 8366 -1697 945 1507 O ANISOU 1666 CD1 LEU B 175 5585 6780 6132 -151 935 1687 c ATOM 1622 N LEU I i 170 0.820 -80.935 -53.548 1.00 66.93 N ATOM 1667 CD2 LEU I ! 175 2.483 -81.036 -43.519 1.00 43.28 c ANISOU 1622 N LEU : B 170 8235 9134 8061 -1488 1042 1179 N ANISOU 1667 CD2 LEU B 175 4711 6557 5176 257 846 1721 c ATOM 1623 CA LEU B 170 0.913 -82.372 -53.725 1.00 74.46 ATOM 1668 C LEU I ! 175 -0.233 -84.397 -42.993 1.00 49.48 c ANISOU 1623 CA LEU B 170 9313 9892 9087 -1728 1083 1200 ANISOU 1668 C LEU B 175 5329 7694 5776 -392 849 2349 c ATOM 1624 CB LEU B 170 1.978 -82.698 -54.774 1.00 80.00 ATOM 1669 O LEU I i 175 0.381 -85.137 -42.221 1.00 60.46 o ANISOU 1624 CB LEU B 170 10220 10248 9930 -1846 1169 973 ANISOU 1669 O LEU B 175 6759 8934 7279 -349 853 2370 o ATOM 1625 CG LEU B 170 1.810 -81.921 -56.083 1.00 86.52 ATOM 1670 N GLN I 3 176 -1.368 -83.794 -42.669 1.00 62.04 N ANISOU 1625 CG LEU B 170 11086 11107 10680 -1967 1174 871 ANISOU 1670 N GLN B 176 6755 9655 7161 -317 817 2513 N i -0.437 -92.000 -39.525 1.00 56.51

6328 8085 7059 -1188 768 3218

-1.530 -91.439 -40.257 1.00 63.53 7132 9239 7769 -1308 754 3281 i -0.465 -93.506 -39.661 1.00 53.47

6054 7481 6782 -1476 751 3316 i 0.778 -91.857 -37.363 1.00 60.09

6708 8509 7614 -728 753 3243

0.945 -92.857 -36.666 1.00 69.84

7956 9652 8928 -785 730 3367

1.720 -90.946 -37.554 1.00 59.94

6747 8355 7673 -514 785 3014

3.000 -91.015 -36.877 1.00 59.17

6716 8017 7749 -317 792 2906

3.946 -89.962 -37.446 1.00 63.09

7287 8360 8327 -145 826 2643

5.285 -89.953 -36.769 1.00 59.41

6876 7657 8039 60 825 2539 i 6.331 -90.736 -37.253 1.00 66.67

7944 8191 9199 -33 873 2417

7.562 -90.739 -36.631 1.00 53.00

6250 6251 7638 153 870 2339

7.751 -89.956 -35.506 1.00 51.54

5968 6239 7377 422 809 2379

8.969 -89.949 -34.874 1.00 56.88

6677 6715 8219 596 793 2313

6.726 -89.173 -35.006 1.00 58.48

6719 7492 8010 522 763 2487

5.506 -89.174 -35.638 1.0049.54

5537 6570 6716 347 776 2568

2.814 -90.809 -35.372 1.00 62.27

6971 8652 8039 -89 741 3070

3.416 -91.509 -34.552 1.00 65.18

7361 8882 8521 -42 723 3128

1.978 -89.836 -35.022 1.00 63.75 i 183 7018 9199 8004 57 719 3146 i i 183 1.655 -89.529 -33.630 1.00 59.44

183 6339 8929 7315 284 678 3305 i i 183 0.732 -88.315 -33.549 1.00 62.04

183 6539 9634 7400 446 673 3344 i 183 1.486 -87.005 -33.558 1.00 62.65 183 6665 9657 7483 722 670 3123 183 2.706 -86.974 -33.385 1.00 62.90 183 6804 9409 7687 825 663 2968 i 183 0.760 -85.907 -33.750 1.00 61.78 183 6474 9816 7184 845 671 3116 o i 183 0.997 -90.675 -32.877 1.00 56.75 o C ASN B 183 5919 8712 6933 143 650 3574

O ASN B 183 1.208 -90.846 -31.675 1.00 60.03

O ASN B 183 6281 9199 7328 298 619 3680 N GLN B 184 0.152 -91.398 -33.578 1.00 59.61 c N GLN B 184 6272 9106 7271 -159 654 3693 c CA GLN B 184 -0.516 -92.551 -33.047 1.00 68.99 c CA GLN B 184 7382 10418 8413 -332 618 3966 c CB GLN B 184 -1.605 -93.021 -33.993 1.00 82.55 c CB GLN B 184 9066 12255 10044 -651 611 4097 c CG GLN B 184 -2.840 -92.143 -34.049 1.00 94.76 c CG GLN B 184 10450 14197 11358 -582 602 4154 c CD GLN B 184 -3.620 -92.416 -35.311 1.00111.99 c CD GLN B 184 12664 16362 13526 -875 574 4106 c OE1 GLN B 184 -3.508 -93.492 -35.884 1.00118.95 c OE1 GLN B 184 13670 16998 14529 -1153 555 4105 o NE2 GLN B 184 -4.391 -91.441 -35.766 1.00116.17 o NE2 GLN B 184 13094 17136 13909 -807 564 4056

C GLN B 184 0.387 -93.705 -32.714 1.00 59.54

C GLN B 184 6312 8866 7442 -434 607 3956 c O GLN B 184 0.184 -94.354 -31.723 1.00 59.88

O GLN B 184 6291 8988 7473 -440 569 4156 N HIS B 185 1.423 -93.911 -33.512 1.00 73.31

N HIS B 185 7831 10418 9606 -826 2814 1752 C HIS I ! 185 2.578 -95.731 -32.338 1.00 85.65

C HIS 185 9529 11590 11424 -909 2458 1760 HIS ] i 185 2.990 -95.013 -31.467 1.00 69.94 HIS I B 185 7860 9395 9321 -717 2189 1713 o i CA HIS I B 185 2.090 -95.186 -33.646 1.00 76.96 c

CA HIS B 185 8123 10728 10391 -1025 2719 1721 i CB HIS I ! 185 3.269 -95.078 -34.603 1.00 68.76 c CB HIS 185 6809 9502 9814 -1233 2580 1525

CG HIS I i 185 3.783 -96.399 -35.083 1.00 76.80

CG HIS B 185 7554 10435 11193 -1483 2578 1493 NDl HIS B 185 4.688 -97.151 -34.375 1.00 73.05

NDl HIS i 185 7172 9659 10925 -1491 2282 1437 c CE1 HIS I 185 4.944 -98.260 -35.036 1.00 66.97 c CE1 HIS : 185 6101 8879 10465 -1733 2360 1418 o NE2 HIS I 185 4.240 -98.256 -36.146 1.00 72.19 o NE2 HB ! 185 6484 9827 11118 -1886 2698 1462

CD2 HIS I 185 3.504 -97.105 -36.198 1.00 79.32

CD2 HIS ! 185 7511 10925 11699 -1731 2834 1511 c N TYR B 186 2.568 -97.042 -32.213 1.00 86.34 c N TYR B 18( 9525 11705 11576 -1030 2538 1848 i

i

i

i

NHl

NHl

B

i

B

i i

i i

B

i

B

i

B B

B

i

B

i

B

i

B

i

i

B

B c i o B o B

B

i

B c i c B c i o B o c c c o B c o c

c i

c i c c c c i c B c B c c i c B c

i i c B

c B o B c B

i c i

c B

c i

c B

c i

B c

i

B

B i

i

B B B B

 ATOM 1 41 N PRO B 209 21.674 -75.369 -45.892 1.00 76.75 N ATOM 1986 N ALA B 215 23.291 -76.996 -38.638 1.00108.50 N ANISOU 1941 N PRO B 209 7921 11351 9890 566 -434 850 N ANISOU 1986 N ALA B 215 11763 15945 13517 289 -2097 2145 N ATOM 1942 CA PRO B 209 22.599 -76.484 -45.683 1.00 74.40 C ATOM 1987 CA ALA B 215 23.247 -75.533 -38.640 1.00106.46 C ANISOU 1942 CA PRO B 209 7432 10936 9902 748 -510 1055 C ANISOU 1987 CA ALA B 215 11553 15863 13033 78 -2095 1939 C ATOM 1943 CB PRO B 209 22.866 -76.460 -44.173 1.00 67.01 C ATOM 1988 CB ALA B 215 22.180 -75.030 -39.599 1.00 99.85 C ANISOU 1943 CB PRO B 209 6433 10164 8865 653 -849 1279 C ANISOU 1988 CB ALA B 215 10919 14943 12077 50 -1765 1655 C ATOM 1944 CG PRO i 209 22.309 -75.152 -43.677 1.00 67.57 C ATOM 1989 C ALA B 215 23.010 -74.983 -37.239 1.00113.63 C ANISOU 1944 CG PRO i 209 6637 10444 8594 417 -926 1159 C ANISOU 1989 C ALA B 215 12643 16967 13564 -146 -2368 2022 C ATOM 1945 CD PRO : i 209 21.194 -74.813 -44.622 1.00 75.22 C ATOM 1990 O ALA B 215 23.570 -73.954 -36.859 1.00119.67 O ANISOU 1945 CD PRO i 209 7831 11340 9410 381 -662 924 C ANISOU 1990 O ALA B 215 13349 17907 14215 -320 -2518 1971 O ATOM 1946 C PRO i 209 22.011 -77.839 -46.067 1.00 81.19 C ATOM 1991 N ASP B 216 22.187 -75.684 -36.470 1.00109.50 N ANISOU 1946 C PRO B 209 8446 11551 10853 884 -388 1083 C ANISOU 1991 N ASP B 216 12357 16404 12846 -150 -2423 2149 N ATOM 1947 O PRO B 209 20.804 -78.063 -45.959 1.00 74.82 O ATOM 1992 CA ASP B 216 21.976 -75.336 -35.075 1.00100.68 C ANISOU 1947 O PRO B 209 7894 10707 9828 799 -368 1027 O ANISOU 1992 CA ASP B 216 11443 15452 11360 -345 -2677 2259 C ATOM 1948 N ASP B 210 22.886 -78.736 -46.506 1.00 98.88 N ATOM 1993 CB ASP B 216 20.602 -74.698 -34.886 1.00 86.77 C ANISOU 1948 N ASP B 210 10522 13614 13433 1093 -300 1177 N ANISOU 1993 CB ASP B 216 10044 13696 9229 -491 -2485 2074 C ATOM 1949 CA ASP B 210 22.538 -80.125 -46.751 1.00105.98 C ATOM 1994 CG ASP B 216 20.473 -73.963 -33.562 1.00 85.74 C ANISOU 1949 CA ASP B 210 11545 14254 14468 1237 -198 1238 C ANISOU 1994 CG ASP B 216 10145 13749 8685 -729 -2696 2112 C ATOM 1950 CB ASP B 210 23.759 -80.852 -47.304 1.00116.33 C ATOM 1995 OD1 ASP B 216 21.070 -74.404 -32.555 1.00 81.84 O ANISOU 1950 CB ASP B 210 12625 15383 16190 1482 -62 1333 C ANISOU 1995 OD1 ASP B 216 9628 13346 8122 -762 -3010 2351 O ATOM 1951 CG ASP B 210 25.039 -80.065 -47.091 1.00113.98 C ATOM 1996 OD2 ASP B 216 19.773 -72.930 -33.537 1.00 86.19 O ANISOU 1951 CG ASP B 210 11981 15260 16066 1504 -160 1426 C ANISOU 1996 OD2 ASP B 216 10418 13852 8477 -884 -2541 1904 O ATOM 1952 OD1 ASP B 210 25.440 -79.884 -45.919 1.00113.95 O ATOM 1997 C ASP B 216 22.099 -76.578 -34.206 1.00103.64 C ANISOU 1952 OD1 ASP B 210 11825 15434 16039 1440 -465 1637 O ANISOU 1997 C ASP B 216 11826 15787 11767 -245 -2889 2578 C ATOM 1953 OD2 ASP B 210 25.635 -79.618 -48.094 1.00107.48 O ATOM 1998 O ASP B 216 21.372 -77.552 -34.423 1.00112.65 O ANISOU 1953 OD2 ASP B 210 11045 14398 15394 1573 64 1290 O ANISOU 1998 O ASP B 216 13072 16750 12979 -109 -2734 2634 O ATOM 1954 C ASP B 210 22.112 -80.772 -45.445 1.00103.09 C ATOM 1999 N PRO B 217 23.005 -76.550 -33.217 1.00102.82 N ANISOU 1954 C ASP B 210 11251 13918 14002 1194 -451 1465 C ANISOU 1999 N PRO B 217 11614 15844 11607 -322 -3252 2797 N ATOM 1955 O ASP B 210 21.257 -81.657 -45.418 1.00102.62 O ATOM 2000 CA PRO B 217 23.112 -77.683 -32.297 1.00105.41 C ANISOU 1955 O ASP 210 11402 13697 13893 1206 -404 1479 O ANISOU 2000 CA PRO B 217 11969 16150 11933 -236 -3474 3127 C ATOM 1956 N ASN 211 22.723 -80.330 -44.354 1.00101.38 N ATOM 2001 CB PRO B 217 24.246 -77.266 -31.358 1.00108.70 C ANISOU 1956 N ASN B ! 211 10862 13907 13751 1134 -724 1649 N ANISOU 2001 CB PRO B 217 12232 16797 12272 -374 -3896 3313 C ATOM 1957 CA ASN B i 211 22.332 -80.813 -43.041 1.00 96.37 C ATOM 2002 CG PRO I i 217 24.243 -75.769 -31.418 1.00106.06 C ANISOU 1957 CA ASN ] B 211 10314 13331 12970 1074 -978 1871 C ANISOU 2002 CG PRO B 217 11982 16616 11699 -620 -3878 3036 C ATOM 1958 CB ASN B ! 211 23.459 -81.586 -42.374 1.00103.55 C ATOM 2003 CD PRO I i 217 23.918 -75.460 -32.848 1.00101.90 C ANISOU 1958 CB ASN I B 211 10969 14213 14163 1233 -1163 2181 C ANISOU 2003 CD PRO B 217 11371 15944 11405 -514 -3488 2757 C ATOM 1959 CG ASN B i 211 23.017 -82.950 -41.924 1.00104.56 C ATOM 2004 C PRO i 217 21.824 -77.866 -31.501 1.00102.07 C ANISOU 1959 CG ASN ] B 211 11226 14144 14360 1342 -1184 2370 C ANISOU 2004 C PRO B 217 11957 15705 11119 -332 -3412 3140 C ATOM 1960 OD1 ASN ] B 211 22.190 -83.079 -41.028 1.00106.42 O ATOM 2005 O PRO B 217 21.486 -78.987 -31.116 1.00101.06 O ANISOU 1960 OD1 ASN ! 211 11661 14442 14333 1220 -1328 2451 O ANISOU 2005 O PRO B 217 11904 15463 11032 -209 -3431 3355 O ATOM 1961 ND2 ASN ] 211 23.534 -83.984 -42.577 1.00103.81 N ATOM 2006 N ASN 218 21.111 -76.768 -31.265 1.00101.95 N ANISOU 1961 ND2 ASN ! 211 11035 13788 14620 1574 -1010 2436 N ANISOU 2006 N ASN B ! 218 12205 15788 10744 -544 -3317 2917 N ATOM 1962 C ASN B 211 21.826 -79.711 -42.131 1.00 85.61 C ATOM 2007 CA ASN B i 218 19.824 -76.817 -30.578 1.00103.23 C ANISOU 1962 C ASN I ! 211 9058 12235 11236 832 -1171 1841 C ANISOU 2007 CA ASN ] B 218 12756 15922 10543 -636 -3198 2906 C ATOM 1963 O ASN B 211 22.604 -78.920 -41.598 1.00 82.44 O ATOM 2008 CB ASN B ! 218 19.442 -75.444 -30.025 1.00 99.42 C ANISOU 1963 O ASN I i 211 8484 12033 10805 754 -1357 1900 O ANISOU 2008 CB ASN I B 218 12534 15599 9644 -898 -3189 2711 C ATOM 1964 N LEU B 212 20.508 -79.666 -41.967 1.00 78.49 N ATOM 2009 CG ASN B i 218 20.028 -75.176 -28.658 1.00 99.11 C ANISOU 1964 N LEU I ! 212 8443 11324 10056 709 -1116 1749 N ANISOU 2009 CG ASN ] B 218 12622 15644 9390 -1032 -3442 2779 C ATOM 1965 CA LEU I i 212 19.887 -78.660 -41.125 1.00 76.93 C ATOM 2010 OD1 ASN ] B 218 20.559 -76.076 -28.006 1.00 96.31 O ANISOU 1965 CA LEU B 212 8390 11344 9495 490 -1243 1711 C ANISOU 2010 OD1 ASN ! 218 12200 15274 9121 -946 -3655 3022 O ATOM 1966 CB LEU I ! 212 18.364 -78.700 -41.257 1.00 75.74 C ATOM 2011 ND2 ASN ] 218 19.919 -73.932 -28.206 1.00 97.11 N ANISOU 1966 CB LEU B 212 8532 11134 9113 393 -1096 1593 C ANISOU 2011 ND2 ASN ! 218 12567 15457 8871 -1234 -3393 2550 N ATOM 1967 CG LEU B 212 17.512 -78.064 -40.154 1.00 72.30 C ATOM 2012 C ASN 218 18.698 -77.336 -31.468 1.00 99.24 C ANISOU 1967 CG LEU B 212 8299 10862 8311 200 -1206 1626 C ANISOU 2012 C ASN B 218 12333 15202 10171 -505 -2830 2785 C ATOM 1968 CD1 LEU I i 212 17.952 -76.639 -39.810 1.00 76.19 C ATOM 2013 O ASN B 218 17.532 -77.322 -31.078 1.00 99.62 O ANISOU 1968 CD1 LEU B 212 8744 11581 8622 52 -1291 1534 C ANISOU 2013 O ASN B 218 12673 15211 9968 -574 -2674 2754 O ATOM 1969 CD2 LEU I i 212 16.058 -78.062 -40.593 1.00 57.26 C ATOM 2014 N ILE B 219 19.045 -77.773 -32.671 1.00 91.90 N ANISOU 1969 CD2 LEU B 212 6619 8877 6260 131 -1005 1494 C ANISOU 2014 N ILE B 219 11149 14132 9636 -325 -2687 2718 N ATOM 1970 C LEU i 212 20.290 -78.872 -39.679 1.00 87.24 C ATOM 2015 CA ILE B 219 18.074 -78.369 -33.572 1.00 84.84 C ANISOU 1970 C LEU B 212 9668 12776 10703 443 -1553 1976 C ANISOU 2015 CA ILE B 219 10319 13027 8889 -208 -2374 2613 C ATOM 1971 O LEU B 212 20.689 -77.926 -38.996 1.00 88.34 O ATOM 2016 CB ILE B 219 17.821 -77.503 -34.803 1.00 80.55 C ANISOU 1971 O LEU B 212 9767 13128 10668 299 -1732 1987 O ANISOU 2016 CB ILE B 219 9718 12462 8424 -227 -2117 2301 C ATOM 1972 N SER B 213 20.194 -80.116 -39.219 1.00 95.53 N ATOM 2017 CGI ILE B 219 17.124 -76.210 -34.395 1.00 82.56 C ANISOU 1972 N SER B 213 10752 13688 11857 556 -1620 2192 N ANISOU 2017 CGI ILE B 219 10199 12859 8310 -441 -2046 2128 C ATOM 1973 CA SER B 213 20.435 -80.437 -37.814 1.00 99.86 C ATOM 2018 CD1 ILE B 219 16.530 -75.441 -35.549 1.00 80.61 C ANISOU 1973 CA SERB 213 11318 14343 12280 514 -1915 2469 C ANISOU 2018 CD1 ILE B 219 9956 12569 8105 -455 -1754 1848 C ATOM 1974 CB SER B 213 20.388 -81.949 -37.578 1.00 98.55 C ATOM 2019 CG2 ILE B 219 16.970 -78.258 -35.816 1.00 73.92 C ANISOU 1974 CB SER B 213 11165 13968 12312 689 -1928 2705 C ANISOU 2019 CG2 ILE B 219 8912 11401 7775 -100 -1840 2216 C ATOM 1975 OG SERB 213 20.275 -82.654 -38.802 1.00 98.47 O ATOM 2020 C ILE B 219 18.564 -79.726 -34.018 1.00 91.93 C ANISOU 1975 OG SER B 213 11126 13704 12585 849 -1657 2587 O ANISOU 2020 C ILE B 219 11024 13737 10167 23 -2383 2788 C ATOM 1976 C SER B 213 21.757 -79.856 -37.325 1.00106.65 C ATOM 2021 O ILE B 219 19.578 -79.835 -34.703 1.00 99.18 O ANISOU 1976 C SER B 213 11918 15398 13208 488 -2173 2586 ANISOU 2021 O ILE B 219 11661 14626 11396 145 -2409 2783 O ATOM 1977 O SER B 213 21.910 -79.529 -36.151 1.00111.35 O ATOM 2022 N ARG B 220 17.847 -80.767 -33.621 1.00 91.03 N ANISOU 1977 O SER B 213 12565 16174 13569 355 -2444 2732 ANISOU 2022 N ARG B 220 11066 13483 10040 86 -2343 2949 N ATOM 1978 N MET B 214 22.699 -79.699 -38.247 1.00111.66 N ATOM 2023 CA ARG B 220 18.286 -82.121 -33.900 1.00 87.09 C ANISOU 1978 N MET B 214 12279 15992 14153 604 -2083 2516 ANISOU 2023 CA ARG B 220 10420 12782 9887 303 -2352 3141 C ATOM 1979 CA MET B 214 24.029 -79.195 -37.930 1.00116.13 C ATOM 2024 CB ARG B 220 18.643 -82.844 -32.603 1.00 99.40 C ANISOU 1979 CA MET B 214 12541 16724 14859 590 -2312 2634 ANISOU 2024 CB ARG B 220 12018 14386 11365 327 -2628 3493 C ATOM 1980 CB MET B 214 25.026 -79.653 -38.995 1.00118.92 C ATOM 2025 CG ARG I 3 220 20.120 -82.856 -32.282 1.00107.39 C ANISOU 1980 CB MET B 214 12578 16926 15679 820 -2152 2648 ANISOU 2025 CG ARG B 220 12740 15515 12548 399 -2921 3686 C ATOM 1981 CG MET B 214 25.832 -80.881 -38.605 1.00124.68 C ATOM 2026 CD ARG I 3 220 20.465 -84.098 -31.477 1.00119.55 C ANISOU 1981 CG MET B 214 13093 17546 16732 1034 -2289 2984 ANISOU 2026 CD ARG B 220 14254 16972 14199 538 -3107 4064 C ATOM 1982 SD MET B 214 24.996 -81.995 -37.456 1.00203.20 S ATOM 2027 NE ARG I 3 220 21.508 -84.894 -32.118 1.00126.77 N ANISOU 1982 SD MET B 214 23302 27421 26484 1045 -2447 3233 ANISOU 2027 NE ARG B 220 14839 17741 15588 782 -3113 4200 N ATOM 1983 CE MET B 214 23.737 -82.718 -38.496 1.00102.87 C ATOM 2028 CZ ARG I i 220 21.759 -86.169 -31.837 1.00129.76 C ANISOU 1983 CE MET B 214 10881 14410 13793 1136 -2041 3008 ANISOU 2028 CZ ARG B 220 15159 17946 16198 974 -3161 4497 C ATOM 1984 C MET B 214 24.070 -77.679 -37.801 1.00111.16 C ATOM 2029 NH1 ARG B 220 22.732 -86.813 -32.470 1.00129.01 N ANISOU 1984 C MET B 214 11941 16320 13975 353 -2371 2439 ANISOU 2029 NH1 ARG B 220 14757 17707 16552 1206 -3131 4609 N ATOM 1985 O MET B 214 24.795 -77.143 -36.960 1.00109.07 O ATOM 2030 NH2 ARG B 220 21.036 -86.807 -30.927 1.00132.27 N ANISOU 1985 O MET B 214 11562 16255 13626 226 -2666 2559 ANISOU 2030 NH2 ARG B 220 15728 18220 16309 942 -3217 4691 N ATOM 2031 C ARG B 220 17.238 -82.915 -34.647 1.00 73.27 C ATOM 2076 O LEU B 225 8.450 -90.790 -42.984 1.00 96.21 O ANISOU 2031 C ARG B 220 8797 10782 8259 378 -2068 3054 C ANISOU 2076 O LEU B 225 12903 11193 12461 226 -164 1981 O ATOM 2032 O ARG B 220 16.046 -82.821 -34.362 1.00 72.31 O ATOM 2077 N PRO B 226 6.367 -91.216 -42.201 1.00 95.47 N ANISOU 2032 O ARG B 220 8920 10648 7906 264 -1954 3002 O ANISOU 2077 N PRO B 226 12979 11064 12232 -57 -165 2132 N ATOM 2033 N PHE B 221 17.702 -83.706 -35.604 1.00 76.14 N ATOM 2078 CA PRO B 226 6.280 -92.330 -43.146 1.00 97.42 C ANISOU 2033 N PHE B 221 8992 10941 8995 566 -1952 3041 N ANISOU 2078 CA PRO B 226 13337 10976 12702 -60 -66 2020 C ATOM 2034 CA PHE B 221 16.843 -84.614 -36.337 1.00 76.47 C ATOM 2079 CB PRO B 226 4.971 -93.030 -42.757 1.00 97.09 C ANISOU 2034 CA PHE B 221 9151 10719 9186 637 -1710 2973 C ANISOU 2079 CB PRO B 226 13415 10801 12674 -241 -49 2135 C ATOM 2035 CB PHE B 221 17.611 -85.244 -37.489 1.00 71.19 C ATOM 2080 CG PRO B 226 4.172 -91.983 -42.048 1.00 93.34 C ANISOU 2035 CB PHE B 221 8284 9845 8918 838 -1576 2914 C ANISOU 2080 CG PRO B 226 12878 10630 11957 -367 -101 2210 C ATOM 2036 CG PHE 3 221 16.893 -86.382 -38.147 1.00 72.78 C ATOM 2081 CD PRO B 226 5.177 -91.119 -41.342 1.00 92.08 C ANISOU 2036 CG PHE B 1 221 8615 9740 9297 919 -1361 2881 C ANISOU 2081 CD PRO B 226 12604 10719 11663 -216 -184 2285 C ATOM 2037 CD1 PHE I B 221 15.934 -86.141 -39.120 1.00 76.27 C ATOM 2082 C PRO B 226 6.223 -91.820 -44.585 1.00 91.99 C ANISOU 2037 CD1 PHE i 221 9194 10100 9683 829 -1135 2607 C ANISOU 2082 C PRO B 226 12663 10298 11992 -125 8 1704 C ATOM 2038 CE1 PHE B 221 15.273 -87.189 -39.737 1.00 76.02 C ATOM 2083 O PRO B 226 5.623 -90.775 -44.853 1.00 83.24 O ANISOU 2038 CE1 PHE B 221 9293 9785 9807 874 -958 2567 C ANISOU 2083 O PRO B 226 11509 9421 10696 -252 -12 1594 O ATOM 2039 CZ PHE B 221 15.573 -88.499 -39.379 1.00 76.06 C ATOM 2084 N GLN B 227 6.869 -92.550 -45.488 1.00 90.49 N ANISOU 2039 CZ PHE B 221 9299 9565 10036 1023 -979 2799 C ANISOU 2084 N GLN B 227 12543 9851 11989 -27 104 1570 N ATOM 2040 CE2 PHE B 221 16.531 -88.751 -38.407 1.00 73.04 C ATOM 2085 CA GLN B 227 6.978 -92.157 -46.885 1.00 84.23 C ANISOU 2040 CE2 PHE B 221 8772 9259 9722 1136 -1190 3089 C ANISOU 2085 CA GLN B 227 11794 9040 11170 -65 188 1272 C ATOM 2041 CD2 PHE B 221 17.184 -87.695 -37.801 1.00 74.16 C ATOM 2086 CB GLN B 227 7.701 -93.240 -47.677 1.00 78.72 C ANISOU 2041 CD2 PHE B 221 8776 9703 9697 1078 -1392 3131 C ANISOU 2086 CB GLN B 227 11219 7987 10703 60 327 1169 C ATOM 2042 C PHE B 221 16.310 -85.682 -35.402 1.00 84.19 C ATOM 2087 CG GLN B 227 9.147 -93.415 -47.305 1.00 80.79 C ANISOU 2042 C PHE B 221 10288 11583 10118 661 -1776 3239 C ANISOU 2087 CG GLN B 227 11355 8208 11133 341 361 1287 C ATOM 2043 O PHE B 221 17.066 -86.343 -34.683 1.00 98.40 O ATOM 2088 CD GLN B 227 9.696 -94.739 -47.786 1.00 95.49 C ANISOU 2043 O PHE B 221 11997 13370 12022 770 -1965 3519 O ANISOU 2088 CD GLN B 227 13353 9661 13269 475 519 1268 C ATOM 2044 N LEU B 222 14.997 -85.853 -35.416 1.00 81.21 N ATOM 2089 OE1 GLN B 227 9.152 -95.801 -47.471 1.00 96.72 O ANISOU 2044 N LEU B 222 10139 11121 9597 558 -1618 3166 N ANISOU 2089 OE1 GLN B 227 13646 9565 13536 417 537 1370 O ATOM 2045 CA LEU B 222 14.344 -86.789 -34.525 1.00 80.21 C ATOM 2090 NE2 GLN B 227 10.772 -94.687 -48.560 1.00100.70 N ANISOU 2045 CA LEU B 222 10186 10885 9403 554 -1648 3407 C ANISOU 2090 NE2 GLN B 227 13980 10234 14048 654 656 1138 N ATOM 2046 CB LEU B 222 13.034 -86.192 -34.028 1.00 74.82 C ATOM 2091 C GLN B 227 5.624 -91.905 -47.527 1.00 89.11 C ANISOU 2046 CB LEU B 222 9743 10304 8383 354 -1564 3337 C ANISOU 2091 C GLN B 227 12506 9696 11655 -329 176 1129 C ATOM 2047 CG LEU B 222 12.665 -86.447 -32.571 1.00 85.34 C ATOM 2092 O GLN B 227 4.626 -92.522 -47.157 1.00 88.83 O ANISOU 2047 CG LEU B 222 11259 11708 9457 287 -1693 3608 C ANISOU 2092 O GLN B 227 12549 9557 11646 -482 146 1231 O ATOM 2048 CD2 LEU B 222 11.926 -87.767 -32.426 1.00 90.23 C ATOM 2093 N GLN B 228 5.596 -90.993 -48.492 1.00 94.73 N ANISOU 2048 CD2 LEU B 222 11999 12070 10214 341 -1586 3778 C ANISOU 2093 N GLN B 228 13198 10560 12233 -384 195 910 N ATOM 2049 CD1 LEU B 222 11.809 -85.305 -32.083 1.00 83.99 C ATOM 2094 CA GLN B 228 4.401 -90.798 -49.297 1.00 93.52 C ANISOU 2049 CD1 LEU B 222 11266 11733 8912 88 -1634 3490 C ANISOU 2094 CA GLN B 228 13132 10429 11970 -627 174 765 C ATOM 2050 C LEU B 222 14.074 -88.082 -35.268 1.00 68.40 C ATOM 2095 CB GLN B 228 3.826 -89.398 -49.126 1.00 85.12 C ANISOU 2050 C LEU B 222 8702 9061 8227 684 -1477 3423 C ANISOU 2095 CB GLN B 228 11926 9723 10693 -715 106 773 C ATOM 2051 O LEU B 222 14.440 -89.169 -34.817 1.00 90.57 O ATOM 2096 CG GLN B 228 2.385 -89.323 -49.573 1.00 78.85 C ANISOU 2051 O LEU B 222 11495 11712 11205 816 -1543 3676 O ANISOU 2096 CG GLN B 228 11176 8961 9824 -974 53 736 C ATOM 2052 N ASP B 223 13.449 -87.950 -36.428 1.00 66.05 N ATOM 2097 CD GLN B 228 1.948 -87.920 -49.899 1.00 80.65 C ANISOU 2052 N ASP B 223 8437 8652 8007 641 -1258 3151 N ANISOU 2097 CD GLN B 228 11286 9498 9858 -1041 24 673 C ATOM 2053 CA ASP B 223 12.876 -89.092 -37.104 1.00 68.40 C ATOM 2098 OE1 GLN B 228 2.002 -87.029 -49.051 1.00 80.98 O ANISOU 2053 CA ASP B 223 8820 8636 8531 693 -1080 3127 C ANISOU 2098 OE1 GLN B 228 11189 9772 9807 -980 14 796 O ATOM 2054 CB ASP B 223 11.741 -89.643 -36.253 1.00 69.52 C ATOM 2099 NE2 GLN B 228 1.521 -87.706 -51.139 1.00 84.72 N ANISOU 2054 CB ASP B 223 9170 8714 8530 587 -1066 3292 C ANISOU 2099 NE2 GLN B 228 11872 10014 10305 -1170 14 481 N ATOM 2055 CG ASP B 223 11.650 -91.139 -36.301 1.00 74.01 C ATOM 2100 C GLN B 228 4.677 -91.064 -50.769 1.00 90.83 C ANISOU 2055 CG ASP B 223 9800 8957 9364 698 -997 3453 C ANISOU 2100 C GLN B 228 12948 9915 11647 -650 264 487 C ATOM 2056 OD1 ASP B 223 11.716 -91.698 -37.418 1.00 77.66 O ATOM 2101 O GLN B 228 5.680 -90.609 -51.322 1.00 93.30 O ANISOU 2056 OD1 ASP B 223 10244 9186 10079 764 -844 3295 O ANISOU 2101 O GLN B 228 13232 10268 11950 -496 344 360 O ATOM 2057 OD2 ASP B 223 11.524 -91.749 -35.218 1.00 85.74 O ATOM 2102 N THR B 229 3.774 -91.805 -51.395 1.00 84.09 N ANISOU 2057 OD2 ASP B 223 11369 10412 10797 716 -1089 3738 O ANISOU 2102 N THR B 229 12268 8866 10816 -855 253 396 N ATOM 2058 C ASP B 223 12.328 -88.681 -38.459 1.00 70.87 C ATOM 2103 CA THR B 229 3.910 -92.155 -52.796 1.00 81.57 C ANISOU 2058 C ASP B 223 9155 8890 8883 621 -880 2795 C ANISOU 2103 CA THR B 229 12154 8357 10481 -917 331 124 C ATOM 2059 O ASP B 223 12.285 -87.497 -38.791 1.00 73.99 O ATOM 2104 CB THR B 229 3.653 -93.650 -53.020 1.00 89.58 C ANISOU 2059 O ASP B 223 9505 9492 9115 530 -871 2606 O ANISOU 2104 CB THR B 229 13402 8970 11665 -1004 382 91 C ATOM 2060 N LYS ] i 224 11.895 -89.665 -39.235 1.00 70.99 N ATOM 2105 OG1 THR B 229 4.468 -94.405 -52.119 1.00 93.66 O ANISOU 2060 N LYS I B 224 9252 8616 9106 652 -723 2729 N ANISOU 2105 OG1 THR B 229 13885 9310 12391 -785 460 270 O ATOM 2061 CA LYS I B 224 11.299 -89.410 -40.534 1.00 71.08 C ATOM 2106 CG2 THR B 229 3.988 -94.051 -54.451 1.00 92.26 C ANISOU 2061 CA LYS B 224 9316 8551 9141 567 -549 2428 C ANISOU 2106 CG2 THR B 229 13998 9081 11978 -1041 497 -207 C ATOM 2062 CB LYS I 3 224 11.991 -90.243 -41.612 1.00 78.77 C ATOM 2107 C THR B 229 2.949 -91.301 -53.606 1.00 74.13 C ANISOU 2062 CB LYS B 224 10257 9247 10425 723 -417 2327 C ANISOU 2107 C THR B 229 11214 7625 9327 -1141 237 -7 C ATOM 2063 CG LYS I 3 224 13.242 -89.615 -42.199 1.00 85.97 C ATOM 2108 O THR B 229 1.940 -90.828 -53.088 1.00 68.42 O ANISOU 2063 CG LYS B 224 10977 10252 11434 859 -410 2221 C ANISOU 2108 O THR B 229 10366 7098 8533 -1288 117 127 O ATOM 2064 CD LYS I 3 224 12.896 -88.333 -42.931 1.00 91.59 C ATOM 2109 N FLE B 230 3.284 -91.080 -54.870 1.00 86.55 N ANISOU 2064 CD LYS B 224 11677 11171 11951 726 -359 1952 C ANISOU 2109 N FLE B 230 12925 9160 10801 -1155 301 -256 N ATOM 2065 CE LYS I 3 224 13.744 -88.137 -44.181 1.00 91.82 C ATOM 2110 CA ILE B 230 2.616 -90.068 -55.666 1.00 97.11 C ANISOU 2065 CE LYS B 224 11616 11127 12146 840 -218 1744 C ANISOU 2110 CA ILE B 230 14237 10741 11919 -1313 216 -368 C ATOM 2066 NZ LYS I 3 224 13.362 -86.877 -44.907 1.00 78.39 N ATOM 2111 C FLE B 230 1.945 -90.697 -56.854 1.00103.87 C ANISOU 2066 NZ LYS B 224 9915 9625 10244 708 -164 1495 N ANISOU 2111 C FLE B 230 15354 11408 12705 -1552 177 -569 C ATOM 2067 C LYS I 3 224 9.821 -89.748 -40.489 1.00 66.39 C ATOM 2112 O ILE B 230 2.503 -91.586 -57.496 1.00103.69 O ANISOU 2067 C LYS B 224 8904 7870 8451 389 -472 2413 C ANISOU 2112 O ILE B 230 15572 11081 12743 -1519 295 -733 O ATOM 2068 O LYS I 3 224 9.417 -90.699 -39.823 1.00 72.47 O ATOM 2113 CB ILE B 230 3.614 -89.040 -56.212 1.00101.03 C ANISOU 2068 O LYS B 224 9771 8484 9280 390 -484 2614 O ANISOU 2113 CB FLE B 230 14673 11407 12307 -1132 317 -491 C ATOM 2069 N LEU B 225 9.010 -88.961 -41.189 1.00 64.95 N ATOM 2114 CGI ILE B 230 4.762 -88.848 -55.229 1.00100.37 C ANISOU 2069 N LEU B 225 8757 7788 8132 237 -393 2192 N ANISOU 2114 CGI ILE B 230 14412 11370 12352 -855 401 -352 C ATOM 2070 CA LEU B 225 7.598 -89.274 -41.350 1.00 69.97 C ATOM 2115 CG2 FLE B 230 2.916 -87.721 -56.492 1.00 99.24 C ANISOU 2070 CA LEU B 225 9530 8334 8720 61 -314 2162 C ANISOU 2115 CG2 ILE B 230 14313 11518 11875 -1244 217 -490 C ATOM 2071 CB LEU B 225 6.863 -88.104 -41.998 1.00 60.51 C ATOM 2116 CD1 FLE B 230 4.298 -88.390 -53.865 1.00100.15 C ANISOU 2071 CB LEU B 225 8319 7329 7344 -89 -262 1951 C ANISOU 2116 CD1 ILE B 230 14163 11556 12332 -857 289 -96 C ATOM 2072 CG LEU B 225 6.184 -87.069 -41.103 1.00 68.75 C ATOM 2117 N ASP B 231 0.749 -90.222 -57.159 1.00110.22 N ANISOU 2072 CG LEU B 225 9360 8637 8126 -203 -296 2031 C ANISOU 2117 N ASP B 231 16112 12388 13377 -1797 13 -552 N ATOM 2073 CD1 LEU B 225 5.432 -86.076 -41.971 1.00 52.06 C ATOM 2118 CA ASP B 231 0.047 -90.694 -58.331 1.00119.46 C ANISOU 2073 CD1 LEU B 225 7226 6654 5903 -332 -216 1820 C ANISOU 2118 CA ASP B 231 17521 13426 14444 -2060 -71 -737 C ATOM 2074 CD2 LEU B 225 5.239 -87.737 -40.117 1.00 79.39 C ATOM 2119 CB ASP B 231 -1.428 -90.904 -58.011 1.00117.13 C ANISOU 2074 CD2 LEU B 225 10814 9911 9442 -287 -293 2256 C ANISOU 2119 CB ASP B 231 17140 13189 14176 -2348 -273 -589 C ATOM 2075 C LEU B 225 7.500 -90.495 -42.247 1.00 90.96 C ATOM 2120 CG ASP B 231 -2.062 -91.964 -58.879 1.00119.36 C ANISOU 2075 C LEU B 225 12279 10654 11628 85 -212 2084 C ANISOU 2120 CG ASP B 231 17703 13198 14450 -2632 -360 -746 C ATOM 2121 OD2 ASP B 231 -2.060 -93.142 -58463 1.00123.34 O ATOM 2166 OD1 ASP B 237 3.867 -95.718 -59.316 1.00117.48 O ANISOU 2121 OD2 ASP B 231 18328 13400 15135 -2666 -316 -719 O ANISOU 2166 OD1 ASP B 237 18343 11438 14856 -1503 793 -1255 ATOM 2122 OD1 ASP B 231 -2.553 -91.624 -59.977 1.00116.74 O ATOM 2167 OD2 ASP B 237 5.302 -96.674 -57.953 1.00113.38 O ANISOU 2122 OD1 ASP B 231 17481 12949 13927 -2827 -476 -894 O ANISOU 2167 OD2 ASP B 237 17683 10636 14759 -1063 1033 -999 O ATOM 2123 C ASP B 231 0.180 -89.661 -59.429 1.00124.08 C ATOM 2168 C ASP B 237 6.823 -92.692 -57.752 1.00104.16 C ANISOU 2123 C ASP B 231 18139 14215 14791 -2074 -80 -903 C ANISOU 2168 C ASP B 237 15774 10559 13243 -643 975 -901 C ATOM 2124 O ASP B 231 0.368 -90.005 -60.598 1.00124.61 O ATOM 2169 O ASP B 237 7.798 -93.371 -57.423 1.00109.02 O ANISOU 2124 O ASP B 231 18480 14125 14741 -2157 -44 -1138 O ANISOU 2169 O ASP B 237 16388 10953 14083 -414 1134 -842 O ATOM 2125 N ARG B 232 0.110 -88.395 -59.020 1.00123.32 N ATOM 2170 N ARG B 238 6.796 -91.372 -57.609 1.00 85.47 N ANISOU 2125 N ARG B 232 17780 14457 14621 -1985 -111 -777 N ANISOU 2170 N ARG B 238 13183 8566 10726 -627 885 -856 N ATOM 2126 CA ARG B 232 -0.134 -87.270 -59.921 1.00120.75 C ATOM 2171 CA ARG B 238 7.854 -90.710 -56.872 1.00 75.40 C ANISOU 2126 CA ARG B 232 17426 14381 14071 -2045 -165 -862 C ANISOU 2171 CA ARG B 238 11637 7464 9546 -364 937 -713 C ATOM 2127 CB ARG B 232 0.000 -85.937 -59.181 1.00111.88 C ATOM 2172 CB ARG B 238 7.801 -89.201 -57.072 1.00 59.15 C ANISOU 2127 CB ARG B 232 16001 13585 12925 -1887 -143 -697 C ANISOU 2172 CB ARG B 238 9408 5782 7285 -383 873 -741 C ATOM 2128 CG ARG I 3 232 -0.742 -85.877 -57.864 1.00106.07 C ATOM 2173 CG ARG I 3 238 9.123 -88.509 -56.843 1.00 75.14 C ANISOU 2128 CG ARG B 232 15031 12955 12316 -1917 -220 -432 C ANISOU 2173 CG ARG B 238 11230 7928 9391 -122 985 -700 C ATOM 2129 CD ARG I 3 232 -2.209 -85.469 -58.008 1.00105.07 C ATOM 2174 CD ARG I 3 238 9.622 -87.841 -58.116 1.00 74.99 C ANISOU 2129 CD ARG B 232 14786 13004 12131 -2161 -397 -311 C ANISOU 2174 CD ARG B 238 11301 7949 9243 -87 1134 -927 C ATOM 2130 NE ARG I 3 232 -2.598 -84.446 -57.033 1.00102.74 N ATOM 2175 NE ARG I 3 238 9.274 -86.424 -58.164 1.00 71.44 N ANISOU 2130 NE ARG B 232 14211 12973 11852 -2086 -388 -91 N ANISOU 2175 NE ARG B 238 10698 7854 8590 -161 1038 -924 N ATOM 2131 CZ ARG I i 232 -2.495 -84.563 -55.707 1.00103.39 C ATOM 2176 CZ ARG I i 238 9.582 -85.605 -59.165 1.00 72.13 C ANISOU 2131 CZ ARG B 232 14166 13057 12060 -1978 -329 ί C ANISOU 2176 CZ ARG B 238 10829 8044 8534 -148 1139 -1087 C ATOM 2132 NH1 ARG B 232 -2.010 -85.668 -55.153 1.00106.19 N ATOM 2177 NH1 ARG B 238 10.257 -86.064 -60.211 1.00 73.10 N ANISOU 2132 NH1 ARG B 232 14622 13172 12555 -1922 -285 97 N ANISOU 2177 NH1 ARG B 238 11154 7943 8679 -66 1348 -1274 N ATOM 2133 NH2 ARG B 232 -2.880 -83.564 -54.922 1.00 97.17 N ATOM 2178 NH2 ARG B 238 9.218 -84.329 -59.123 1.00 74.26 N ANISOU 2133 NH2 ARG B 232 13161 12505 11252 -1924 -304 264 N ANISOU 2178 NH2 ARG B 238 10953 8624 8636 -213 1051 -1059 N ATOM 2134 C ARG B 232 0.720 -87.255 -61.183 1.00123.82 C ATOM 2179 C ARG B 238 7.633 -91.057 -55.409 1.00 80.76 C ANISOU 2134 C ARG B 232 18068 14661 14315 -1982 -40 -1130 C ANISOU 2179 C ARG B 238 12141 8179 10367 -330 815 -430 C ATOM 2135 O ARG I 3 232 1.802 -87.840 -61.236 1.00127.43 O ATOM 2180 O ARG I 3 238 6.511 -91.365 -55.010 1.00 88.18 O ANISOU 2135 O ARG B 232 18660 14895 14864 -1803 145 -1238 O ANISOU 2180 O ARG B 238 13114 9123 11268 -531 675 -347 O ATOM 2136 N ALA I 3 233 0.206 -86.564 -62.193 1.00120.79 N ATOM 2181 N VAL I 3 239 8.685 -91.044 -54.603 1.00 61.80 N ANISOU 2136 N ALA I B 233 17744 14441 13709 -2128 -136 -1220 N ANISOU 2181 N VAL BI 239 9553 5796 8130 -83 863 -269 N ATOM 2137 CA ALA ] B 233 0.765 -86.589 -63.536 1.00116.54 C ATOM 2182 CA VAL BI 239 8.494 -91.237 -53.173 1.00 68.99 C ANISOU 2137 CA ALA i 233 17497 13801 12983 -2134 -43 -1479 C ANISOU 2182 CA VAL B 239 10301 6784 9129 -54 730 12 C ATOM 2138 CB ALA B 233 -0.140 -85.839 -64.479 1.00107.16 C ATOM 2183 CB VAL I i 239 9.048 -92.578 -52.653 1.00 71.55 C ANISOU 2138 CB ALA B 233 16337 12833 11546 -2350 -225 -1507 C ANISOU 2183 CB VAL BI 239 10684 6779 9724 98 811 149 C ATOM 2139 C ALA B 233 2.178 -86.031 -63.620 1.00121.46 C ATOM 2184 CGI VAL I B 239 8.890 -92.661 -51.144 1.00 70.00 C ANISOU 2139 C ALA B 233 18098 14440 13613 -1826 209 -1559 C ANISOU 2184 CGI VAL i 239 10316 6699 9580 133 663 457 C ATOM 2140 O ALA B 233 2.563 -85.150 -62.850 1.00114.68 O ATOM 2185 CG2 VAL B 239 8.342 -93.746 -53.324 1.00 66.73 C ANISOU 2140 O ALA B 233 16960 13791 12823 -1646 255 -1414 O ANISOU 2185 CG2 VAL B 239 10371 5819 9166 -59 879 19 C ATOM 2141 N GLY B 234 2.941 -86.548 -64.579 1.00131.81 N ATOM 2186 C VAL B 239 9.087 -90.084 -52.385 1.00 64.72 C ANISOU 2141 N GLY B 234 19712 15519 14852 -1777 377 -1794 N ANISOU 2186 C VAL B 239 9482 6579 8531 69 653 148 C ATOM 2142 CA GLY B 234 4.302 -86.103 -64.805 1.00135.87 C ATOM 2187 O VAL B 239 10.280 -89.810 -52.465 1.00 59.43 O ANISOU 2142 CA GLY B 234 20222 16017 15387 -1495 639 -1881 C ANISOU 2187 O VAL B 239 8696 5928 7957 276 742 145 O ATOM 2143 C GLY B 234 5.242 -86.488 -63.680 1.00145.69 C ATOM 2188 N TYR B 240 8.230 -89.400 -51.637 1.00 67.75 N ANISOU 2143 C GLY B 234 21283 17151 16921 -1239 781 -1761 C ANISOU 2188 N TYR B 240 9763 7217 8761 -68 496 267 N ATOM 2144 O GLY B 234 6.353 -85.964 -63.591 1.00144.33 O ATOM 2189 CA TYR B 240 8.658 -88.287 -50.811 1.00 65.26 C ANISOU 2144 O GLY B 234 20997 17026 16817 -994 965 -1764 O ANISOU 2189 CA TYR B 240 9220 7215 8360 10 414 391 C ATOM 2145 N ILE B 235 4.800 -87.415 -62.832 1.00155.51 N ATOM 2190 CB TYR B 240 7.656 -87.153 -50.891 1.00 52.70 C ANISOU 2145 N ILE B 235 22497 18248 18342 -1301 691 -1644 N ANISOU 2190 CB TYR B 240 7591 5902 6530 -175 334 345 C ATOM 2146 CA ILE B 235 5.556 -87.799 -61.636 1.00151.99 C ATOM 2191 CG TYR B 240 7.664 -86.410 -52.188 1.00 74.23 C ANISOU 2146 CA ILE B 235 21860 17721 18167 -1076 779 -1482 C ANISOU 2191 CG TYR B 240 10365 8702 9136 -222 410 106 C ATOM 2147 CB ILE B 235 5.568 -86.633 -60.600 1.00138.87 C ATOM 2192 CD2 TYR B 240 8.281 -85.175 -52.299 1.00 61.95 C ANISOU 2147 CB ILE B 235 19830 16407 16528 -976 694 -1265 C ANISOU 2192 CD2 TYR B 240 8667 7384 7486 -145 433 57 C ATOM 2148 CGI ILE B 235 6.451 -86.947 -59.398 1.00133.39 C ATOM 2193 CE2 TYR B 240 8.276 -84.488 -53.489 1.00 58.98 C ANISOU 2148 CGI ILE B 235 18946 15655 16081 -744 768 -1098 C ANISOU 2193 CE2 TYR B 240 8343 7073 6994 -185 512 -147 C ATOM 2149 CD1 ILE B 235 6.095 -86.150 -58.163 1.00130.97 C ATOM 2194 CZ TYR B 240 7.650 -85.036 -54.593 1.00 73.55 C ANISOU 2149 CD1 ILE B 235 18341 15632 15789 -731 630 -864 C ANISOU 2194 CZ TYR B 240 10398 8755 8795 -311 552 -310 C ATOM 2150 CG2 ILE B 235 4.155 -86.247 -60.171 1.00138.70 C ATOM 2195 OH TYR B 240 7.640 -84.358 -55.788 1.00 68.54 O ANISOU 2150 CG2 ILE B 235 19690 16594 16418 -1204 457 -1123 C ANISOU 2195 OH TYR B 240 9835 8189 8018 -355 622 -503 O ATOM 2151 C ILE B 235 5.438 -89.236 -61.087 1.00142.70 C ATOM 2196 CE1 TYR B 240 7.028 -86.262 -54.504 1.00 82.85 C ANISOU 2151 C ILE B 235 20772 16287 17161 -1179 708 -1404 C ANISOU 2196 CE1 TYR B 240 11725 9696 10060 -406 515 -277 C ATOM 2152 O ILE B 235 5.874 -89.548 -59.976 1.00140.03 O ATOM 2197 CD1 TYR B 240 7.046 -86.938 -53.307 1.00 78.22 C ANISOU 2152 O ILE B 235 20222 16016 16969 -1147 617 -1182 O ANISOU 2197 CD1 TYR B 240 11073 9037 9611 -356 455 -69 C ATOM 2153 N LYS B 236 4.812 -90.119 -61.856 1.00134.69 N ATOM 2198 C TYR B 240 8.757 -88.702 -49.364 1.00 70.75 C ANISOU 2153 N LYS B 236 20092 14965 16120 -1310 759 -1589 N ANISOU 2198 C TYR B 240 9821 7925 9135 74 311 669 C ATOM 2154 CA LYS I 3 236 4.291 -91.359 -61.308 1.00125.94 C ATOM 2199 O TYR B 240 8.005 -89.556 -48.894 1.00 71.35 O ANISOU 2154 CA LYS B 236 19078 13600 15174 -1431 693 -1518 C ANISOU 2199 O TYR B 240 9993 7856 9259 -15 271 782 O ATOM 2155 CB LYS I 3 236 3.765 -92.287 -62.409 1.00123.68 C ATOM 2200 N SER B 241 9.675 -88.075 -48.649 1.00 73.13 N ANISOU 2155 CB LYS B 236 19193 13022 14779 -1680 688 -1754 C ANISOU 2200 N SER B 241 9938 8407 9441 217 259 784 N ATOM 2156 CG LYS I 3 236 4.774 -93.247 -62.975 1.00118.98 C ATOM 2201 CA SER B 241 9.734 -88.242 -47.215 1.00 74.30 C ANISOU 2156 CG LYS B 236 18898 12028 14280 -1530 968 -1943 C ANISOU 2201 CA SERB 241 10000 8633 9596 255 131 1053 C ATOM 2157 CD LYS I 3 236 4.067 -94.332 -63.757 1.00112.62 C ATOM 2202 CB SER B 241 10.872 -89.179 -46.813 1.00 70.03 C ANISOU 2157 CD LYS B 236 18491 10902 13397 -1819 930 -2138 C ANISOU 2202 CB SER B 241 9402 7902 9304 474 144 1206 C ATOM 2158 CE LYS I 3 236 4.027 -94.031 -65.238 1.00104.95 C ATOM 2203 OG SERB 241 12.097 -88.479 -46.758 1.00 76.28 O ANISOU 2158 CE LYS B 236 17842 9922 12115 -1963 964 -2425 C ANISOU 2203 OG SER B 241 10001 8845 10137 627 128 1215 O ATOM 2159 NZ LYS I 3 236 3.192 -95.049 -65.931 1.00104.61 N ATOM 2204 C SER B 241 9.921 -86.870 -46.586 1.00 69.65 C ANISOU 2159 NZ LYS B 236 18184 9594 11969 -2301 868 -2607 N ANISOU 2204 C SER B 241 9258 8389 8816 236 34 1094 C ATOM 2160 C LYS I 3 236 5.300 -92.055 -60.400 1.00119.11 C ATOM 2205 O SER B 241 10.463 -85.956 -47.209 1.00 61.40 O ANISOU 2160 C LYS B 236 18129 12531 14598 -1157 862 -1394 C ANISOU 2205 O SER B 241 8128 7480 7720 269 78 945 O ATOM 2161 O LYS I 3 236 6.496 -92.105 -60.695 1.00119.34 O ATOM 2206 N ASN B 242 9.454 -86.732 -45.354 1.00 70.57 N ANISOU 2161 O LYS B 236 18197 12439 14707 -913 1088 -1475 O ANISOU 2206 N ASN B 242 9359 8634 8819 174 -83 1293 N ATOM 2162 N ASP I 3 237 4.804 -92.535 -59.266 1.00115.87 N ATOM 2207 CA ASN B 242 9.621 -85.505 -44.603 1.00 52.13 C ANISOU 2162 N ASP I B 237 17577 12100 14348 -1191 748 -1174 N ANISOU 2207 CA ASN B 242 6916 6601 6288 145 -173 1345 C ATOM 2163 CA ASP 1 B 237 5.586 -93.357 -58.351 1.00113.72 C ATOM 2208 CB ASN B 242 8.276 -84.819 -44.395 1.00 60.04 C ANISOU 2163 CA ASP i 237 17244 11612 14352 -966 869 -1023 C ANISOU 2208 CB ASN B 242 7990 7750 7073 -47 -167 1325 C ATOM 2164 CB ASP B 237 5.972 -94.673 -59.022 1.00116.41 C ATOM 2209 CG ASN B 242 7.598 -84.466 -45.700 1.00 59.03 C ANISOU 2164 CB ASP B 237 17924 11493 14814 -954 1059 -1194 C ANISOU 2209 CG ASN B 242 7909 7604 6916 -148 -62 1098 C ATOM 2165 CG ASP B 237 4.978 -95.769 -58.750 1.00117.04 C ATOM 2210 OD1 ASN B 242 6.952 -85.311 -46.322 1.00 58.02 O ANISOU 2165 CG ASP B 237 18161 11333 14975 -1189 957 -1152 C ANISOU 2210 OD1 ASN B 242 7889 7279 6877 -214 -15 1047 O ATOM 2211 ND2 ASN B 242 7.762 -83.217 -46.138 1.00 53.49 N ATOM 2256 O LEU ] S 247 13.601 -78.584 -28.525 1.00101.58 O ANISOU 2211 ND2 ASN B 242 7135 7103 6086 -168 -32 962 N ANISOU 2256 O LEU B 247 13950 15240 9404 -719 -2252 3052 O ATOM 2212 C ASN B 242 10.268 -85.802 -43.267 1.00 57.66 C ATOM 2257 N LEU ] S 248 15.337 -77.259 -28.929 1.00 97.94 N ANISOU 2212 C ASN B 242 7555 7349 7005 236 -311 1601 C ANISOU 2257 N LEU I B 248 13204 15014 8995 -808 -2533 2872 N ATOM 2213 O ASN B 242 10.037 -86.858 -42.681 1.00 55.55 O ATOM 2258 CA LEU I B 248 15.681 -77.234 -27.525 1.00102.92 C ANISOU 2213 O ASN B 242 7361 6918 6829 261 -342 1778 O ANISOU 2258 CA LEU B 248 13989 15685 9431 -871 -2718 2957 C ATOM 2214 N SER B 243 11.069 -84.863 -42.781 1.00 55.40 N ATOM 2259 CB LEU I 3 248 17.048 -77.859 -27.315 1.00 99.32 C ANISOU 2214 N SER B 243 7141 7285 6625 275 -402 1628 N ANISOU 2259 CB LEU B 248 13268 15289 9182 -786 -3067 3174 C ATOM 2215 CA SER B 243 11.867 -85.090 -41.589 1.00 57.61 C ATOM 2260 CG LEU B 248 17.505 -78.935 -28.285 1.00 89.53 C ANISOU 2215 CA SERB 243 7346 7628 6916 362 -567 1868 C ANISOU 2260 CG LEU B 248 11732 13958 8327 -574 -3135 3398 C ATOM 2216 CB SER B 243 13.307 -84.661 -41.827 1.00 63.12 C ATOM 2261 CD1 LEU I i 248 18.782 -79.583 -27.795 1.00 79.76 C ANISOU 2216 CB SER B 243 7842 8405 7736 496 -620 1842 C ANISOU 2261 CD1 LEU B 248 10273 12766 7264 -494 -3462 3619 C ATOM 2217 OG SER B 243 13.840 -85.318 -42.955 1.00 80.80 O ATOM 2262 CD2 LEU I i 248 16.441 -79.989 -28.464 1.00 86.34 C ANISOU 2217 OG SER B 243 10033 10425 10241 630 -482 1733 O ANISOU 2262 CD2 LEU B 248 11471 13373 7962 -465 -2956 3547 C ATOM 2218 C SER B 243 11.320 -84.377 -40.367 1.00 64.20 C ATOM 2263 C LEU i 248 15.661 -75.850 -26.900 1.00110.24 C ANISOU 2218 C SER B 243 8245 8683 7465 232 -676 1988 C ANISOU 2263 C LEU B 248 15107 16704 10077 -1056 -2680 2719 C ATOM 2219 O SER B 243 10.816 -83.258 -40.456 1.00 64.72 O ATOM 2264 O LEU I 3 248 16.100 -74.882 -27.510 1.00111.08 O ANISOU 2219 O SER B 243 8335 8926 7328 111 -634 1858 O ANISOU 2264 O LEU B 248 15104 16889 10211 -1136 -2663 2524 O ATOM 2220 N ILE B 244 11.450 -85.032 -39.219 1.00 63.60 N ATOM 2265 N GLU I B 249 15.133 -75.757 -25.685 1.00107.55 N ANISOU 2220 N ILE B 244 8209 8586 7370 265 -803 2245 N ANISOU 2265 N GLU 3 249 15057 16340 9469 -1115 -2653 2742 N ATOM 2221 CA ILE B 244 10.965 -84.496 -37.958 1.00 70.32 C ATOM 2266 CA GLU I 3 249 15.349 -74.591 -24.850 1.00107.14 C ANISOU 2221 CA ILE B 244 9162 9621 7935 149 -899 2383 C ANISOU 2266 CA GLU B 249 15188 16371 9148 -1280 -2695 2581 C ATOM 2222 CB ILE B 244 10.158 -85.544 -37.200 1.00 69.84 C ATOM 2267 CB GLU I i 249 14.046 -73.874 -24.516 1.00104.50 C ANISOU 2222 CB ILE B 244 9254 9415 7867 127 -893 2598 C ANISOU 2267 CB GLU B 249 15161 15953 8592 -1335 -2345 2400 C ATOM 2223 CG1 ILE B 244 9.018 -86.055 -38.068 1.00 65.43 C ATOM 2268 CG GLU I 3 249 14.199 -72.367 -24.602 1.00112.35 C ANISOU 2223 CG1 ILE B 244 8778 8668 7413 60 -708 2479 C ANISOU 2268 CG GLU B 249 16190 16986 9514 -1464 -2220 2115 C ATOM 2224 CD1 ILE B 244 8.306 -87.231 -37.472 1.00 61.07 C ATOM 2269 CD GLU I 3 249 12.937 -71.598 -24.308 1.00116.37 C ANISOU 2224 CD1 ILE B 244 8355 7926 6923 46 -687 2687 C ANISOU 2269 CD GLU B 249 16973 17393 9850 -1486 -1858 1956 C ATOM 2225 CG2 ILE B 244 9.621 -84.972 -35.901 1.00 69.56 C ATOM 2270 OE1 GLU : B 249 12.294 -71.123 -25.256 1.00114.53 O ANISOU 2225 CG2 ILE B 244 9354 9562 7512 6 -958 2737 C ANISOU 2270 OE1 GLU B 249 16688 17090 9737 -1447 -1588 1818 O ATOM 2226 ILE B 244 12.135 -84.060 -37.093 1.00 71.63 C ATOM 2271 OE2 GLU B 249 12.599 -71.444 -23.129 1.00118.74 O ANISOU 2226 ILE B 244 9228 9966 8023 197 -1109 2515 C ANISOU 2271 OE2 GLU B 249 17527 17685 9903 -1535 -1841 1979 O ATOM 2227 ILE B 244 13.123 -84.779 -36.970 1.00 78.15 O ATOM 2272 C GLU B 249 16.060 -75.028 -23.586 1.00112.53 C ANISOU 2227 ILE B 244 9935 10711 9049 343 -1221 2660 O ANISOU 2272 C GLU B 249 15940 17113 9703 -1295 -2986 2781 C ATOM 2228 TYR B 245 12.022 -82.886 -36.487 1.00 68.99 N ATOM 2273 O GLU I i 249 15.608 -75.930 -22.908 1.00121.73 O ANISOU 2228 TYR B 245 8942 9867 7403 70 -1165 2472 N ANISOU 2273 O GLU B 249 17245 18207 10801 -1213 -2959 2961 O ATOM 2229 CA TYR B 245 13.115 -82.332 -35.708 1.00 72.23 C ATOM 2274 N ASN I i 250 17.176 -74.399 -23.262 1.00109.84 N ANISOU 2229 CA TYR B 245 9267 10466 7710 73 -1385 2567 C ANISOU 2274 N ASN I B 250 15489 16903 9341 -1402 -3266 2758 N ATOM 2230 CB TYR B 245 13.679 -81.097 -36.398 1.00 64.00 C ATOM 2275 CA ASN I B 250 17.925 -74.807 -22.090 1.00120.61 C ANISOU 2230 CB TYR B 245 8094 9572 6649 33 -1360 2334 C ANISOU 2275 CA ASN B 250 16880 18349 10596 -1432 -3585 2949 C ATOM 2231 CG TYR B 245 14.442 -81.406 -37.660 1.00 65.21 C ATOM 2276 CB ASN I i 250 17.037 -74.702 -20.868 1.00129.25 C ANISOU 2231 CG TYR B 245 8040 9603 7134 178 -1284 2215 C ANISOU 2276 CB ASN B 250 18374 19422 11314 -1509 -3484 2933 C ATOM 2232 CD1 TYR B 245 13.778 -81.569 -38.876 1.00 54.88 C ATOM 2277 CG ASN ] 3 250 16.461 -73.322 -20.696 1.00131.19 C ANISOU 2232 CD1 TYR B 245 6758 8147 5946 196 -1057 2021 C ANISOU 2277 CG ASN ] B 250 18854 19662 11329 -1665 -3254 2636 C ATOM 2233 CE1 TYR B 245 14.472 -81.854 -40.029 1.00 54.85 C ATOM 2278 OD1 ASN ] B 250 17.194 -72.338 -20.649 1.00136.26 O ANISOU 2233 CE1 TYR B 245 6604 8020 6216 326 -965 1905 C ANISOU 2278 OD1 ASN B 250 19487 20399 11888 -1826 -3399 2501 O ATOM 2234 CZ TYR B 245 15.857 -81.982 -39.979 1.00 68.45 C ATOM 2279 ND2 ASN ] i 250 15.145 -73.237 -20.596 1.00125.70 N ANISOU 2234 CZ TYR B 245 8113 9761 8133 456 -1084 1995 C ANISOU 2279 ND2 ASN B 250 18357 18845 10557 -1615 -2884 2540 N ATOM 2235 OH TYR B 245 16.572 -82.265 -41.122 1.00 56.99 O ATOM 2280 C ASN 3 250 18.472 -76.226 -22.190 1.00117.49 C ANISOU 2235 OH TYR B 245 6515 8174 6964 599 -956 1886 O ANISOU 2280 C ASN B 250 16252 17930 10458 -1252 -3789 3263 C ATOM 2236 CE2 TYR B 245 16.538 -81.824 -38.782 1.00 60.73 C ATOM 2281 O ASN B 250 18.643 -76.908 -21.198 1.00115.12 O ANISOU 2236 CE2 TYR B 245 7070 8940 7067 439 -1330 2204 C ANISOU 2281 O ASN B 250 16056 17641 10045 -1222 -3947 3465 O ATOM 2237 CD2 TYR B 245 15.829 -81.538 -37.637 1.00 62.09 C ATOM 2282 N GLY B 251 18.753 -76.666 -23.399 1.00114.76 N ANISOU 2237 CD2 TYR B 245 7425 9238 6929 294 -1436 2305 C ANISOU 2282 N GLY B 251 15594 17546 10465 -1123 -3773 3307 N ATOM 2238 C TYR B 245 12.680 -81.971 -34.301 1.00 83.23 C ATOM 2283 CA GLY B 251 19.474 -77.898 -23.590 1.00114.27 C ANISOU 2238 C TYR B 245 10854 12009 8759 -58 -1493 2719 C ANISOU 2283 CA GLY B 251 15272 17440 10708 -934 -3950 3600 C ATOM 2239 O TYR B 245 11.529 -81.603 -34.075 1.00 91.08 O ATOM 2284 C GLY B 251 18.570 -79.078 -23.477 1.00117.08 C ANISOU 2239 O TYR B 245 12031 13023 9552 -176 -1350 2666 O ANISOU 2284 C GLY B 251 15777 17634 11072 -792 -3773 3761 C ATOM 2240 N GLU B 246 13.596 -82.083 -33.348 1.00 81.90 N ATOM 2285 O GLY B 251 19.023 -80.206 -23.568 1.00120.17 O ANISOU 2240 N GLU 3 246 10650 11947 8522 -37 -1745 2920 N ANISOU 2285 O GLY B 251 15997 17947 11714 -619 -3876 4017 O ATOM 2241 CA GLU I 3 246 13.318 -81.576 -32.018 1.00 86.01 C ATOM 2286 N GLN B 252 17.283 -78.811 -23.313 1.00117.47 N ANISOU 2241 CA GLU B 246 11379 12635 8666 -181 -1862 3037 C ANISOU 2286 N GLN B 252 16142 17620 10870 -860 -3490 3617 N ATOM 2242 CB GLU I i 246 13.632 -82.606 -30.927 1.00 96.92 C ATOM 2287 CA GLN B 252 16.277 -79.854 -23.204 1.00119.13 C ANISOU 2242 CB GLU B 246 12823 13982 10019 -120 -2064 3373 C ANISOU 2287 CA GLN B 252 16504 17669 11090 -748 -3281 3747 C ATOM 2243 CG GLU I 3 246 15.082 -82.672 -30.488 1.00108.60 C ATOM 2288 CB GLN B 252 15.707 -79.884 -21.791 1.00131.29 C ANISOU 2243 CG GLU B 246 14118 15577 11567 -58 -2379 3537 C ANISOU 2288 CB GLN B 252 18387 19205 12292 -800 -3256 3816 C ATOM 2244 CD GLU I 3 246 15.432 -84.013 -29.872 1.00123.05 C ATOM 2289 CG GLN B 252 14.357 -80.573 -21.648 1.00137.67 C ANISOU 2244 CD GLU B 246 15927 17289 13536 82 -2530 3876 C ANISOU 2289 CG GLN B 252 19424 19854 13030 -744 -2935 3850 C ATOM 2245 OE1 GLU : B 246 15.051 -84.262 -28.705 1.00123.49 O ATOM 2290 CD GLN B 252 14.341 -81.963 -22.230 1.00142.83 C ANISOU 2245 OE1 GLU B 246 16203 17395 13321 13 -2630 4085 O ANISOU 2290 CD GLN B 252 19942 20349 13976 -568 -2922 4101 C ATOM 2246 OE2 GLU B 246 16.076 -84.827 -30.566 1.00130.20 O ATOM 2291 OE1 GLN B 252 15.237 -82.340 -22.975 1.00145.38 O ANISOU 2246 OE2 GLU B 246 16606 18037 14825 269 -2528 3938 C ANISOU 2291 OE1 GLN B 252 19974 20662 14603 -463 -3103 4226 O ATOM 2247 C GLU B 246 14.092 -80.290 -31.806 1.00 84.01 C ATOM 2292 NE2 GLN B 252 13.313 -82.731 -21.903 1.00143.70 N ANISOU 2247 C GLU B 246 11073 12613 8235 -290 -2001 2917 C ANISOU 2292 NE2 GLN B 252 20262 20321 14018 -529 -2687 4179 N ATOM 2248 O GLU I 3 246 15.216 -80.127 -32.291 1.00 79.50 O ATOM 2293 C GLN B 252 15.171 -79.620 -24.209 1.00108.97 C ANISOU 2248 O GLU B 246 10260 12086 7862 -222 -2124 2880 O ANISOU 2293 C GLN B 252 15261 16285 9856 -749 -2939 3567 C ATOM 2249 N LEU I S 247 13.462 -79.370 -31.091 1.00 90.72 N ATOM 2294 O GLN B 252 14.888 -78.498 -24.572 1.00101.43 O ANISOU 2249 N LEU I B 247 12154 13596 8720 -463 -1958 2852 N ANISOU 2294 O GLN B 252 14387 15385 8765 -870 -2790 3308 O ATOM 2250 CA LEU I B 247 14.046 -78.076 -30.811 1.00 95.56 C ATOM 2295 N ARG B 253 14.539 -80.701 -24.640 1.00112.48 N ANISOU 2250 CA LEU B 247 12776 14414 9120 -603 -2065 2718 C ANISOU 2295 N ARG B 253 15778 18102 8859 -576 -1105 2972 N ATOM 2251 CB LEU I 3 247 13.072 -76.983 -31.208 1.00 87.34 C ATOM 2296 CA ARG B 253 13.600 -80.650 -25.738 1.00106.03 C ANISOU 2251 CB LEU B 247 11875 13397 7914 -718 -1790 2466 C ANISOU 2296 CA ARG B 253 14840 17175 8273 -515 -806 2892 C ATOM 2252 CG LEU B 247 12.490 -77.211 -32.592 1.00 81.32 C ATOM 2297 CB ARG B 253 13.054 -82.041 -26.039 1.00104.27 C ANISOU 2252 CG LEU B 247 10978 12481 7440 -614 -1537 2308 C ANISOU 2297 CB ARG B 253 14450 16845 8323 -417 -672 3195 C ATOM 2253 CD1 LEU I i 247 11.454 -76.169 -32.813 1.00 82.23 C ATOM 2298 CG ARG ] i 253 11.713 -82.084 -26.750 1.00104.17 C ANISOU 2253 CD1 LEU B 247 11241 12629 7372 -726 -1284 2116 C ANISOU 2298 CG ARG B 253 14318 16730 8534 -366 -351 3144 C ATOM 2254 CD2 LEU I i 247 13.584 -77.114 -33.638 1.00 75.08 C ATOM 2299 CD ARG ] i 253 11.300 -83.510 -27.032 1.00106.79 C ANISOU 2254 CD2 LEU B 247 9894 11687 6947 -517 -1600 2194 C ANISOU 2299 CD ARG B 253 14518 16937 9121 -299 -232 3446 C ATOM 2255 C LEU i 247 14.319 -77.990 -29.330 1.00 99.21 C ATOM 2300 NE ARG I i 253 12.413 -84.313 -27.519 1.00109.44 N ANISOU 2255 C LEU B 247 13437 15018 9241 -720 -2306 2914 C ANISOU 2300 NE ARG B 253 14665 17183 9734 -239 -489 3644 N

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 C ATOM 2886 CG GLU I i 328 12.697 -66.895 -36.085 1.00108.87 C ANISOU 2886 CG GLU B 328 14955 16138 10272 -527 -56 -445 O ATOM 2887 CD GLU I i 328 13.614 -65.709 -35.959 1.00117.73 O ANISOU 2887 CD GLU B 328 16269 17203 11260 -702 -218 -676 N ATOM 2888 OE1 GLU : B 328 13.467 -64.924 -34.994 1.00123.80 N ANISOU 2888 OE1 GLU B 328 17383 17974 11682 -788 -134 -864 C ATOM 2889 OE2 GLU B 328 14.484 -65.578 -36.826 1.00117.61 O C ANISOU 2889 OE2 GLU B 328 16069 17136 11482 -760 -421 -667 o C ATOM 2890 C GLU B 328 11.466 -69.457 -34.393 1.00 94.75 c C ANISOU 2890 C GLU B 328 13139 14679 8182 -414 124 61 c C ATOM 2891 O GLU I i 328 10.273 -69.160 -34.489 1.00104.29 o C ANISOU 2891 O GLU B 328 14372 15807 9448 -285 445 -1 o C ATOM 2892 N VAL I i 329 11.922 -70.692 -34.547 1.00 87.98 N C ANISOU 2892 N VAL I B 329 12074 13904 7450 -415 -57 323 N C ATOM 2893 CA VAL I B 329 11.021 -71.789 -34.843 1.00 76.45 c C ANISOU 2893 CA VAL B 329 10427 12428 6194 -289 108 539 c C ATOM 2894 CB VAL I i 329 11.776 -73.066 -35.218 1.00 63.80 c C ANISOU 2894 CB VAL I B 329 8603 10858 4780 -296 -128 800 c

C ATOM 2895 CGI VAL I B 329 10.790 -74.173 -35.534 1.00 55.84 c C ANISOU 2895 CGI VAL i 329 7434 9800 3982 -192 50 1004 c C ATOM 2896 CG2 VAL B 329 12.669 -72.807 -36.413 1.00 53.65 c C ANISOU 2896 CG2 VAL B 329 7130 9460 3794 -301 -320 732 c C ATOM 2897 C VAL B 329 10.123 -72.062 -33.654 1.00 77.23 c

C ANISOU 2897 C VAL B 329 10716 12641 5989 -270 339 614 c o ATOM 2898 O VAL I 3 329 8.917 -72.254 -33.806 1.00 81.90 o o ANISOU 2898 O VAL B 329 11236 13182 6700 -158 627 659 o

N ATOM 2899 N LEU I 3 330 10.720 -72.072 -32.467 1.00 85.03 N

N ANISOU 2899 N LEU I B 330 11940 13791 6576 -387 210 640 N C ATOM 2900 CA LEU I B 330 9.979 -72.305 -31.232 1.00 87.54 c c ANISOU 2900 CA LEU B 330 12487 14236 6537 -383 426 712 c c ATOM 2901 CB LEU I i 330 10.918 -72.294 -30.031 1.00 86.76 c c ANISOU 2901 CB LEU B 330 12655 14329 5981 -548 185 740 c o ATOM 2902 CG LEU B 330 11.548 -73.642 -29.702 1.00 86.00 c o ANISOU 2902 CG LEU B 330 12431 14371 5876 -583 -58 1083 c c ATOM 2903 CD1 LEU I i 330 12.777 -73.452 -28.833 1.00 89.09 c c ANISOU 2903 CD1 LEU B 330 12998 14849 6001 -733 -401 1072 c o ATOM 2904 CD2 LEU I i 330 10.523 -74.525 -29.009 1.00 82.24 c o ANISOU 2904 CD2 LEU B 330 12003 13964 5282 -509 208 1303 c

N ATOM 2905 C LEU i 330 8.916 -71.244 -31.044 1.00 83.28 c

N ANISOU 2905 C LEU B 330 12128 13614 5899 -303 794 476 c c ATOM 2906 O LEU B 330 7.772 -71.545 -30.702 1.00 69.29 o c ANISOU 2906 O LEU B 330 10360 11860 4109 -199 1116 565 o c ATOM 2907 N ARG B 331 9.323 -69.998 -31.256 1.00 89.37 N c ANISOU 2907 N ARG B 331 13049 14292 6618 -350 752 188 N c ATOM 2908 CA ARG B 331 8.427 -68.857 -31.161 1.00 99.06 c c ANISOU 2908 CA ARG B 331 14462 15399 7778 -256 1098 -59 c c ATOM 2909 CB ARG B 331 9.116 -67.599 -31.675 1.00101.32 c c ANISOU 2909 CB ARG B 331 14854 15538 8105 -326 969 -348 c c ATOM 2910 CG ARG B 331 8.181 -66.445 -31.847 1.00100.55 c c ANISOU 2910 CG ARG B 331 14892 15262 8051 -189 1331 -581 c

ATOM 2911 CD ARG B 331 8.909 -65.180 -32.265 1.00102.02 c ANISOU 2911 CD ARG B 331 15229 15284 8249 -280 1203 -866 c ATOM 2912 NE ARG B 331 8.630 -64.744 -33.637 1.00100.43 N ANISOU 2912 NE ARG B 331 14763 14893 8504 -153 1255 -906 N ATOM 2913 CZ ARG B 331 7.418 -64.585 -34.172 1.00100.26 c ANISOU 2913 CZ ARG B 331 14591 14765 8738 65 1582 -876 c ATOM 2914 NHl ARG B 331 6.315 -64.840 -33.479 1.00105.24 N ANISOU 2914 NHl ARG B 331 15280 15458 9249 197 1919 -801 N ATOM 2915 NH2 ARG B 331 7.307 -64.168 -35.426 1.00 96.48 N ANISOU 2915 NH2 ARG B 331 13888 14127 8643 152 1569 -904 N ATOM 2916 C ARG B 331 7.147 -69.115 -31.945 1.00 98.93 C ANISOU 2916 C ARG B 331 14170 15281 8140 -56 1405 36 c c ATOM 2917 O ARG B 331 6.054 -69.081 -31.383 1.00 99.18 o c ANISOU 2917 O ARG B 331 14280 15336 8067 53 1759 64 o o ATOM 2918 N HIS B 332 7.291 -69.397 -33.238 1.00 96.73 N o ANISOU 2918 N HIS B 332 13562 14899 8292 -15 1265 100 N

N ATOM 2919 CA HIS B 332 6.155 -69.778 -34.076 1.00 90.75 C N ANISOU 2919 CA HIS B 332 12508 14064 7909 138 1479 223 c c ATOM 2920 CB HIS B 332 6.599 -70.048 -35.513 1.00 80.89 c i c ANISOU 2920 CB HIS B 332 10961 12703 7070 138 1249 262 c c ATOM 2921 CG HIS B 332 7.070 -68.842 -36.254 1.00 82.31 c c ANISOU 2921 CG HIS B 332 11183 12737 7355 141 1178 18 c c ATOM 2922 NDl HIS B 332 8.304 -68.271 -36.036 1.00 93.69 N i c ANISOU 2922 NDl HIS B 332 12801 14178 8618 6 936 -133 N c ATOM 2923 CE1 HIS B 332 8.453 -67.233 -36.838 1.00 90.28 c i c ANISOU 2923 CE1 HIS B 332 12366 13587 8349 32 936 -322 c o ATOM 2924 NE2 HIS B 332 7.363 -67.112 -37.572 1.00 78.63 N 3 o ANISOU 2924 NE2 HIS B 332 10717 12015 7143 191 1161 -291 N

N ATOM 2925 CD2 HIS B 332 6.484 -68.109 -37.226 1.00 76.20 C 3 N ANISOU 2925 CD2 HIS B 332 10287 11810 6855 254 1308 -80 c c ATOM 2926 C HIS B 332 5.508 -71.052 -33.563 1.00 93.35 c c ANISOU 2926 C HIS B 332 12730 14519 8220 153 1585 509 c o ATOM 2927 O HIS B 332 4.306 -71.252 -33.702 1.00 95.85 o ί 327 o ANISOU 2927 O HIS B 332 12899 14821 8699 264 1866 608 o

N ATOM 2928 N LEU B 333 6.321 -71.936 -33.000 1.00 97.34 N ί 328 N ANISOU 2928 N LEU B 333 13290 15146 8550 37 1350 663 N i c ATOM 2929 CA LEU B 333 5.851 -73.270 -32.662 1.00 92.43 c c ANISOU 2929 CA LEU B 333 12544 14613 7963 38 1403 965 c i c ATOM 2930 CB LEU B 333 7.021 -74.184 -32.310 1.00 86.42 c c ANISOU 2930 CB LEU B 333 11808 13945 7081 -78 1066 1134

Table 8. DMXAA-hSTING^sl62A/Q2661 complex REMARK 3 T33: 0.2519 T12: 0.0735

REMARK 3 T13: 0.0755 T23: 0.0818

REMARK 3 L TENSOR

REMARK 3 Ll l : 5.9722 L22: 1.3349

REMARK 3 REMARK 3 L33: 1.7568 L12: -1.1178

REMARK 3 REFINEMENT. REMARK 3 L13: -0.3822 L23: 0.2016

REMARK 3 PROGRAM : PHENIX (phenix.refme: 1.8.2 1309) REMARK 3 S TENSOR

REMARK 3 AUTHORS : Adams,Afonine,Burnley,Chen,Davis,Echols,Gildea, REMARK 3 SI 1 : 0.2128 S12: 0.9436 S13: ■0.0733

REMARK 3 : Gopal,Gros,Grosse-Kunstleve,Headd,Hung,Immormino, REMARK 3 S21 : -0.3067 S22: -0.3874 S23: -0.1726

REMARK 3 : Ioerger,McCoy,McKee,Moriarty,Pai,Read,Richardson, REMARK 3 S31 : -0.0468 S32: 0.1617 S33: 0.1883

REMARK 3 : Richardson,Romo,Sacchettini,Sauter,Smith,Storoni, REMARK 3 TLS GROUP : 2

REMARK 3 : Terwilliger,Zwart REMARK 3 SELECTION: chain Ά' and (resid 186 through 197 )

REMARK 3 REMARK 3 ORIGIN FOR THE GROUP (A): 190.7984 42.0205 -3.5854

REMARK 3 REFINEMENT TARGET : ML REMARK 3 T TENSOR

REMARK 3 REMARK 3 Ti l 0.3433 T22 0.7278

REMARK 3 DATA USED IN REFINEMENT. REMARK 3 T33 0.9942 T12 0.0625

REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.420 REMARK 3 T13 0.0145 T23 -0.1884

REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 128.132 REMARK 3

REMARK 3 MIN(FOBS/SIGMA FOBS) : 1.37 REMARK 3 Ll l 0.6328 L22 1.4550

REMARK 3 COMPLETENESS FOR RANGE (%) : 99.92 REMARK 3 L33 1.9966 L12 0.9561

REMARK 3 NUMBER OF REFLECTIONS : 17687 REMARK 3 L13 -1.1238 L23 -1.7024

REMARK 3 NUMBER OF REFLECTIONS (NON-ANOMALOUS) : 17687 REMARK 3 S TENSOR

REMARK 3 REMARK 3 SI 1 : 0.2236 S12: 2.5099 S13 0.4877

REMARK 3 FLT TO DATA USED IN REFINEMENT. REMARK 3 S21 : 0.3243 S22: 0.4937 S23 -0.6010

REMARK 3 R VALUE (WORKTNG + TEST SET) : 0.1849 REMARK 3 S31 : 0.4014 S32: 0.9611 S33 -0.3780

REMARK 3 R VALUE (WORKING SET) : 0.1826 REMARK 3 TLS GROUP : 3

REMARK 3 FREE R VALUE : 0.2288 REMARK 3 SELECTION: chain Ά' and (resid 198 through 211 )

REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.09 REMARK 3 ORIGIN FOR THE GROUP (A): 170.7088 39.7653 7.4402

REMARK 3 FREE R VALUE TEST SET COUNT : 900 REMARK 3 T TENSOR

REMARK 3 REMARK 3 Ti l 0.2740 T22: 0.4544

REMARK 3 FLT TO DATA USED IN REFINEMENT (IN BINS). REMARK 3 T33 0.4040 T12: 0.0404

REMARK 3 BIN RESOLUTION RANGE COMPL. NWORK NFREE RWORK REMARK 3 T13 -0.0470 T23: 0.0714

RFREE REMARK 3

REMARK 3 1 128.3118 - 4.3975 1.00 2916 153 0.1666 0.2093 REMARK 3 Ll l 5.7895 L22 3.3168

REMARK 3 2 4.3975 - 3.4904 1.00 2807 157 0.1516 0.1892 REMARK 3 L33 4.0196 L12 1.5375

REMARK 3 3 3.4904 - 3.0491 1.00 2768 152 0.17840.2393 REMARK 3 L13 -1.1285 L23 -0.3983

REMARK 3 4 3.0491 - 2.7703 1.00 2762 163 0.2125 0.2572 REMARK 3 S TENSOR

REMARK 3 5 2.7703 - 2.5717 1.00 2785 124 0.2508 0.2956 REMARK 3 SI 1 : 0.2141 S12: -1.2485 S13: -0.3878

REMARK 3 6 2.5717 - 2.4201 1.00 2749 151 0.3209 0.3813 REMARK 3 S21 : 0.4935 S22: 0.0116 S23: -0.0676

REMARK 3 REMARK 3 S31 : 0.0221 S32: 0.3522 S33: -0.0548

REMARK 3 BULK SOLVENT MODELLING. REMARK 3 TLS GROUP : 4

REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL REMARK 3 SELECTION: chain Ά' and (resid 212 through 224 )

REMARK 3 SOLVENT RADIUS : 1.11 REMARK 3 ORIGIN FOR THE GROUP (A): 183.4756 40.9208 10.1738

REMARK 3 SHRINKAGE RADIUS : 0.90 REMARK 3 T TENSOR

REMARK 3 GRID STEP FACTOR : 4.00 REMARK 3 Ti l 0.4807 T22 0.3883

REMARK 3 REMARK 3 T33 0.4005 T12 -0.0833

REMARK 3 ERROR ESTIMATES. REMARK 3 T13 0.0009 T23 -0.0042

REMARK 3 COORDINATE ERROR (MAXIMUM -LIKELIHOOD BASED) : 0.36 REMARK 3

REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : REMARK 3 Ll l 1.4467 L22 7.9564

23.15 REMARK 3 L33 2.3372 L12 0.3458

REMARK 3 REMARK 3 L13 0.8944 L23 -3.1919

REMARK 3 STRUCTURE FACTORS CALCULATION ALGORITHM : FFT REMARK 3 S TENSOR

REMARK 3 REMARK 3 SI 1 : -0.2837 S12: -0.0988 S13: 0.1904

REMARK 3 DEVIATIONS FROM IDEAL VALUES. REMARK 3 S21 : 0.6346 S22: 0.1878 S23: -0.8066

REMARK 3 RMSD MAX COUNT REMARK 3 S31 : -0.6748 S32: 0.1563 S33: -0.0333

REMARK 3 BOND : 0.014 0.122 3030 REMARK 3 TLS GROUP : 5

REMARK 3 ANGLE : 1.613 32.388 4116 REMARK 3 SELECTION: chain Ά' and (resid 225 through 280 )

REMARK 3 CHIRALITY : 0.094 0.461 444 REMARK 3 ORIGIN FOR THE GROUP (A): 172.8424 46.4350 4.7085

REMARK 3 PLANARLTY : 0.006 0.049 542 REMARK 3 T TENSOR

REMARK 3 DIHEDRAL : 19.567 88.200 1134 REMARK 3 Ti l 0.2443 T22: 0.2704

REMARK 3 MIN NONBONDED DISTANCE : 1.815 REMARK 3 T33 0.3434 T12: -0.0185

REMARK 3 REMARK 3 T13 -0.0020 T23: 0.0299

REMARK 3 MOLPROBLTY STATISTICS. REMARK 3

REMARK 3 ALL-ATOM CLASHSCORE : 7.69 REMARK 3 Ll l 2.4041 L22 1.1461

REMARK 3 RAMACHANDRAN PLOT: REMARK 3 L33 1.2070 L12 -1.6704

REMARK 3 OUTLIERS : 0.00 % REMARK 3 L13 -0.6579 L23 0.4071

REMARK 3 ALLOWED : 2.50 % REMARK 3 S TENSOR

REMARK 3 FAVORED : 97.50 % REMARK 3 SI 1 : -0.0871 S12: 0.2281 S13: 0.3173

REMARK 3 ROTAMER OUTLIERS : 11.78 % REMARK 3 S21 : -0.0231 S22: -0.0117 S23: -0.3709

REMARK 3 CBETA DEVIATIONS : 1 REMARK 3 S31 : -0.0217 S32: 0.0440 S33: 0.0348

REMARK 3 REMARK 3 TLS GROUP : 6

REMARK 3 ATOMIC DISPLACEMENT PARAMETERS. REMARK 3 SELECTION: chain Ά' and (resid 281 through 300 )

REMARK 3 WILSON B : 51.93 REMARK 3 ORIGIN FOR THE GROUP (A): 158.8087 37.1274 2.4555

REMARK 3 RMS(B ISO OR EQUIVALENT BONDED) : 5.80 REMARK 3 T TENSOR

REMARK 3 ATOMS NUMBER OF ATOMS REMARK 3 Ti l 0.3605 T22 0.3488

REMARK 3 ISO. ANISO. REMARK 3 T33 0.2887 T12 -0.0224

REMARK 3 ALL : 3043 2920 REMARK 3 T13 -0.0733 T23: -0.0596

REMARK 3 ALL (NO H) : 3043 2920 REMARK 3

REMARK 3 SOLVENT : 71 0 REMARK 3 Ll l 4.6775 L22 2.9261

REMARK 3 NON-SOLVENT : 2972 2920 REMARK 3 L33 2.9523 L12 0.9648

REMARK 3 HYDROGENS : 0 0 REMARK 3 L13 -3.4362 L23 -1.5127

REMARK 3 REMARK 3 S TENSOR

REMARK 3 TLS DETAILS. REMARK 3 Sl l -0.3680 S12: 0.2443 S13: -0.4711

REMARK 3 NUMBER OF TLS GROUPS: 12 REMARK 3 S21 0.1364 S22: -0.0570 S23: -0.3094

REMARK 3 ORIGIN: CENTER OF MASS REMARK 3 S31 0.9835 S32: -0.6684 S33: 0.3625

REMARK 3 TLS GROUP : 1 REMARK 3 TLS GROUP : 7

REMARK 3 SELECTION: chain 'A' and (resid 154 through 185 ) REMARK 3 SELECTION: chain Ά' and (resid 301 through 314 )

REMARK 3 ORIGIN FOR THE GROUP (A): 172.7210 47.3865 -5.8660 REMARK 3 ORIGIN FOR THE GROUP (A): 170.2562 38.6578 -7.1494

REMARK 3 T TENSOR REMARK 3 T TENSOR

REMARK 3 Ti l : 0.2534 T22: 0.3103 REMARK 3 Ti l : 0.5190 T22: 0.6208



 ATOM 136 CD1 LEU A 170 168420 54.284 -5.108 1.00 56.58 C ATOM 181 CA GLN A 176 181.055 45.127 -10.476 1.00 59.62

ANISOU 136 CD1 LEU A 170 7199 7095 7205 649 580 1481 C ANISOU 181 CA GLN A 176 6588 9245 6820 1347 1432 1122

ATOM 137 CD2 LEU A 170 168.233 54.157 -7.595 1.00 61.54 c ATOM 182 CB GLN A 176 180.661 44.404 -11.748 1.00 69.15

ANISOU 137 CD2 LEU A 170 7734 8231 7416 953 655 1680 c ANISOU 182 CB GLN A 176 7752 10731 7793 1529 1414 845

ATOM 138 C LEU A 170 172.022 51.631 -7.291 1.00 51.30 c ATOM 183 CG GLN A 176 179.248 43.921 -11.722 1.00 84.31

ANISOU 138 C LEU A 170 6325 7032 6135 801 824 1540 c ANISOU 183 CG GLN A 176 9737 12605 9692 1578 1337 572

ATOM 139 O LEU A 170 172.978 52.226 -7.755 1.00 58.75 o ATOM 184 CD GLN A 176 179.136 42.455 -12.086 1.00 97.37

ANISOU 139 O LEU A 170 7202 8040 7081 810 919 1783 o ANISOU 184 CD GLN A 176 11337 14269 11391 1690 1298 145 C

ATOM 140 N FLE A 171 172.183 50.540 -6.562 1.00 45.53 N ATOM 185 OE1 GLN A 176 178.572 42.101 -13.129 1.00102.93 O

ANISOU 140 N FLE A 171 5616 6211 5474 737 784 1316 N ANISOU 185 OE1 GLN A 176 12011 15190 11909 1790 1240 -100 o

ATOM 141 CA FLE A 171 173.528 50.113 -6.177 1.00 38.25 c ATOM 186 NE2 GLN A 176 179.685 41.586 -11.232 1.00100.03 N

ANISOU 141 CA ILE A 171 4645 5247 4642 673 839 1356 c ANISOU 186 NE2 GLN A 176 11658 14345 12006 1659 1311 56 N

ATOM 142 CB FLE A 171 173.558 49.581 -4.693 1.00 54.60 c ATOM 187 C GLN A 176 182.234 46.050 -10.777 1.00 58.38 C

ANISOU 142 CB FLE A 171 6760 7082 6903 536 773 1224 c ANISOU 187 C GLN A 176 6366 9163 6651 1281 1475 1420 c

ATOM 143 CGI ILE A 171 174.905 49.836 -4.068 1.00 54.95 c ATOM 188 O GLN A 176 183.389 45.691 -10.557 1.00 62.58 o

ANISOU 143 CGI FLE A 171 6747 7053 7078 439 813 1356 c ANISOU 188 O GLN A 176 6817 9683 7276 1266 1514 1443 o

ATOM 144 CD1 ILE A 171 175.067 51.316 -3.748 1.00 59.62 c ATOM 189 N ALA A 177 181.931 47.239 -11.283 1.00 53.99 N

ANISOU 144 CD1 FLE A 171 7331 7529 7794 342 817 1539 c ANISOU 189 N ALA A 177 5833 8667 6014 1250 1461 1640 N

ATOM 145 CG2 ILE A 171 173.276 48.107 -4.588 1.00 55.70 c ATOM 190 CA ALA A 177 182.965 48.208 -11.613 1.00 51.61 c

ANISOU 145 CG2 FLE A 171 6901 7231 7031 579 746 988 c ANISOU 190 CA ALA A 177 5452 8398 5759 1194 1497 1914 c

ATOM 146 C FLE A 171 174.107 49.068 -7.143 1.00 35.71 C ATOM 191 CB ALA A 177 182.385 49.410 -12.334 1.0041.97 c

ANISOU 146 C FLE A 171 4247 5162 4159 805 898 1256 C ANISOU 191 CB ALA A 177 4237 7246 4464 1212 1482 2120 c

ATOM 147 O FLE A 171 175.289 49.068 -7.451 1.00 48.25 O ATOM 192 C ALA A 177 183.647 48.632 -10.331 1.00 54.09 c

ANISOU 147 O FLE A 171 5758 6840 5736 819 983 1380 O ANISOU 192 C ALA A 177 5772 8412 6369 1002 1474 2017 c

ATOM 148 N LEU A 172 173.279 48.165 -7.633 1.00 38.21 N ATOM 193 O ALA A 177 184.864 48.741 -10.281 1.00 59.93 o

ANISOU 148 N LEU A 172 4568 5587 4362 903 853 1006 N ANISOU 193 O ALA A 177 6414 9165 7190 962 1511 2111 o

ATOM 149 CA LEU A 172 173.772 47.037 -8.415 1.00 44.51 C ATOM 194 N ARG A 178 182.867 48.847 -9.275 1.00 48.28 N

ANISOU 149 CA LEU A 172 5283 6576 5051 1025 893 824 C ANISOU 194 N ARG A 178 5139 7421 5784 885 1403 1977 N

ATOM 150 CB LEU A 172 172.658 46.005 -8.629 1.0047.45 C ATOM 195 CA ARG A 178 183.472 49.247 -8.018 1.00 47.16 c

ANISOU 150 CB LEU A 172 5661 6966 5403 1085 814 479 C ANISOU 195 CA ARG A 178 4994 7025 5902 708 1352 2026 c

ATOM 151 CG LEU A 172 172.259 45.226 -7.375 1.00 48.68 C ATOM 196 CB ARG A 178 182.410 49.647 -7.008 1.00 42.63 c

ANISOU 151 CG LEU A 172 5874 6801 5822 957 753 335 C ANISOU 196 CB ARG A 178 4540 6207 5451 594 1258 1970 c

ATOM 152 CD1 LEU A 172 171.335 44.085 -7.733 1.00 51.07 C ATOM 197 CG ARG A 178 181.715 50.932 -7.412 1.00 37.36 c

ANISOU 152 CD1 LEU A 172 6139 7113 6151 1017 699 -13 C ANISOU 197 CG ARG A 178 3913 5483 4798 562 1227 2079 c

ATOM 153 CD2 LEU A 172 173.490 44.698 -6.612 1.00 42.38 C ATOM 198 CD ARG A 178 180.454 51.157 -6.528 1.00 42.44 c

ANISOU 153 CD2 LEU A 172 5054 5849 5199 893 803 409 C ANISOU 198 CD ARG A 178 4686 5923 5518 485 1135 1976 c

ATOM 154 C LEU A 172 174.415 47.406 -9.765 1.00 51.61 C ATOM 199 NE ARG A 178 180.816 51.341 -5.120 1.00 40.41 N

ANISOU 154 C LEU A 172 6082 7828 5701 1177 990 960 C ANISOU 199 NE ARG A 178 4434 5452 5468 327 1058 1911 N

ATOM 155 O LEU A 172 175.421 46.807 -10.142 1.00 57.40 O ATOM 200 CZ ARG A 178 180.109 50.884 -4.094 1.00 44.12 c

ANISOU 155 O LEU A 172 6731 8684 6397 1238 1062 924 O ANISOU 200 CZ ARG A 178 4987 5796 5981 276 986 1778 c

ATOM 156 N PRO A 173 173.819 48.353 -10.518 1.00 50.56 N ATOM 201 NHl ARG A 178 178.997 50.213 -4.326 1.00 44.59 N

ANISOU 156 N PRO A 173 5942 7881 5385 1256 998 1123 N ANISOU 201 NHl ARG A 178 5136 5887 5920 359 990 1701 N

ATOM 157 CA PRO A 173 174.427 48.673 -11.822 1.00 57.61 C ATOM 202 NH2 ARG A 178 180.519 51.082 -2.842 1.00 45.29 N

ANISOU 157 CA PRO A 173 6718 9161 6009 1420 1105 1291 C ANISOU 202 ΝΉ2 ARG A 178 5114 5811 6282 150 915 1726 N

ATOM 158 CB PRO A 173 173.648 49.907 -12.277 1.00 57.66 C ATOM 203 C ARG A 178 184.386 48.174 -7.464 1.00 47.72 C

ANISOU 158 CB PRO A 173 6741 9236 5930 1459 1081 1534 C ANISOU 203 C ARG A 178 4994 7106 6032 721 1377 1934 c

ATOM 159 CG PRO A 173 172.249 49.662 -11.693 1.00 55.73 C ATOM 204 O ARG A 178 185.439 48.475 -6.911 1.00 47.05 o

ANISOU 159 CG PRO A 173 6596 8840 5739 1424 960 1305 C ANISOU 204 O ARG A 178 4831 6954 6090 626 1364 2010 o

ATOM 160 CD PRO A 173 172.509 49.013 -10.349 1.00 52.05 C ATOM 205 N FLE A 179 183.958 46.926 -7.634 1.00 48.20 N

ANISOU 160 CD PRO A 173 6207 7997 5572 1240 913 1138 C ANISOU 205 N FLE A 179 5066 7251 5995 852 1412 1750 N

ATOM 161 C PRO A 173 175.928 48.981 -11.773 1.00 59.73 C ATOM 206 CA FLE A 179 184.694 45.760 -7.193 1.00 48.50 C

ANISOU 161 C PRO A 173 6920 9399 6375 1361 1202 1522 C ANISOU 206 CA ILE A 179 5025 7286 6115 910 1439 1634 c

ATOM 162 O PRO A 173 176.638 48.581 -12.685 1.00 61.49 O ATOM 207 CB FLE A 179 183.815 44.516 -7.290 1.00 51.23 c

ANISOU 162 O PRO A 173 7041 9870 6451 1470 1235 1483 O ANISOU 207 CB FLE A 179 5430 7600 6437 1037 1413 1356 c

ATOM 163 N GLU A 174 176.411 49.662 -10.738 1.00 56.89 N ATOM 208 CGI ILE A 179 182.643 44.624 -6.342 1.00 60.80 c

ANISOU 163 N GLU A 174 6606 8720 6288 1178 1205 1708 N ANISOU 208 CGI FLE A 179 6794 8553 7754 925 1289 1294 c

ATOM 164 CA GLU A 174 177.823 50.037 -10.719 1.00 54.95 C ATOM 209 CD1 ILE A 179 183.063 44.561 -4.944 1.00 62.50 c

ANISOU 164 CA GLU A 174 6278 8426 6174 1107 1253 1877 C ANISOU 209 CD1 FLE A 179 7012 8566 8169 802 1223 1362 c

ATOM 165 CB GLU A 174 178.022 51.509 -10.342 1.00 57.70 C ATOM 210 CG2 ILE A 179 184.581 43.302 -6.871 1.00 50.72 c

ANISOU 165 CB GLU A 174 6626 8541 6756 969 1227 2109 C ANISOU 210 CG2 FLE A 179 5289 7472 6509 1109 1417 1232 c

ATOM 166 CG GLU A 174 177.490 52.511 -11.355 1.00 67.68 C ATOM 211 C FLE A 179 185.942 45.532 -8.055 1.00 51.38 c

ANISOU 166 CG GLU A 174 7846 9937 7930 1062 1234 2282 C ANISOU 211 C FLE A 179 5265 7862 6394 999 1508 1661 c

ATOM 167 CD GLU A 174 178.155 52.387 -12.725 1.00 80.62 C ATOM 212 O FLE A 179 187.017 45.249 -7.538 1.00 50.58 o

ANISOU 167 CD GLU A 174 9352 11927 9351 1225 1306 2387 C ANISOU 212 O FLE A 179 5076 7729 6412 969 1513 1697 o

ATOM 168 OE1 GLU A 174 179.293 51.839 -12.802 1.00 84.29 O ATOM 213 N ARG A 180 185.771 45.628 -9.372 1.00 52.67 N

ANISOU 168 OE1 GLU A 174 9751 12469 9807 1223 1357 2372 O ANISOU 213 N ARG A 180 5415 8263 6336 1117 1554 1639 N

ATOM 169 OE2 GLU A 174 177.522 52.844 -13.714 1.00 83.96 O ATOM 214 CA ARG A 180 186.860 45.449 -10.326 1.00 60.20 c

ANISOU 169 OE2 GLU A 174 9728 12564 9610 1361 1309 2485 O ANISOU 214 CA ARG A 180 6249 9456 7170 1212 1624 1662 c

ATOM 170 C GLU A 174 178.634 49.172 -9.779 1.00 48.63 C ATOM 215 CB ARG A 180 186.346 45.651 -11.753 1.00 69.09 c

ANISOU 170 C GLU A 174 5472 7486 5521 1023 1279 1768 C ANISOU 215 CB ARG A 180 7373 10861 8017 1345 1651 1638 c

ATOM 171 O GLU A 174 179.766 49.496 -9.461 1.00 51.76 O ATOM 216 CG ARG A 180 186.513 44.452 -12.661 1.00 77.82 c

ANISOU 171 O GLU A 174 5808 7792 6067 933 1297 1887 O ANISOU 216 CG ARG A 180 8412 12202 8954 1535 1683 1356 c

ATOM 172 N LEU A 175 178.077 48.067 -9.327 1.0045.45 N ATOM 217 CD ARG A 180 185.184 44.024 -13.309 1.00 83.31 c

ANISOU 172 N LEU A 175 5120 7024 5125 1047 1236 1495 N ANISOU 217 CD ARG A 180 9174 13008 9474 1649 1632 1109 c

ATOM 173 CA LEU A 175 178.783 47.309 -8.305 1.00 47.79 C ATOM 218 NE ARG A 180 185.152 44.261 -14.760 1.00 90.87 N

ANISOU 173 CA LEU A 175 5414 7115 5629 957 1211 1394 C ANISOU 218 NE ARG A 180 10069 14328 10130 1783 1647 1114

ATOM 174 CB LEU A 175 177.864 46.317 -7.610 1.0044.51 C ATOM 219 CZ ARG A 180 185.845 43.559 -15.666 1.00 93.66

ANISOU 174 CB LEU A 175 5086 6510 5314 938 1104 1111 C ANISOU 219 CZ ARG A 180 10312 14935 10339 1920 1685 951

ATOM 175 CG LEU A 175 178.599 45.713 -6.426 1.00 46.88 C ATOM 220 NHl ARG A 180 186.643 42.567 -15.276 1.00 95.47

ANISOU 175 CG LEU A 175 5378 6598 5836 844 1083 1096 C ANISOU 220 NHl ARG A 18C 10486 15066 10723 1941 1717 765

ATOM 176 CD1 LEU A 175 178.824 46.798 -5.403 1.00 43.61 C ATOM 221 ΝΉ2 ARG A 180 185.745 43.846 -16.965 1.00 89.93 N

ANISOU 176 CD1 LEU A 175 4996 6023 5553 675 1051 1302 C ANISOU 221 NH2 ARG A 18C 9774 14822 9574 2048 1687 980 N

ATOM 177 CD2 LEU A 175 177.785 44.579 -5.867 1.00 48.55 C ATOM 222 C ARG A 180 187.936 46.479 -10.019 1.00 63.20 c

ANISOU 177 CD2 LEU A 175 5645 6641 6161 849 1008 853 C ANISOU 222 C ARG A 180 6557 9780 7675 1073 1633 1926 c

ATOM 178 C LEU A 175 180.048 46.608 -8.827 1.00 56.12 C ATOM 223 O ARG A 180 189.132 46.195 -10.045 1.00 69.21 o

ANISOU 178 C LEU A 175 6337 8351 6634 1052 1309 1376 C ANISOU 223 O ARG A 180 7206 10615 8477 1086 1676 1953 o

ATOM 179 O LEU A 175 181.137 46.765 -8.251 1.00 54.98 O ATOM 224 N THR A 181 187.481 47.680 -9.701 1.00 59.04 N

ANISOU 179 O LEU A 175 6131 8128 6630 967 1347 1515 O ANISOU 224 N THR A 181 6091 9106 7237 939 1587 2092 N

ATOM 180 N GLN A 176 179.914 45.859 -9.921 1.00 57.81 N ATOM 225 CA THR A 181 188.355 48.787 -9.363 1.00 60.45 c

ANISOU 180 N GLN A 176 6490 8828 6645 1234 1345 1188 N ANISOU 225 CA THR A 181 6199 9182 7588 793 1581 2295 c

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



 ATOM 586 O LEU A 225 184.123 51.853 -0.680 1.00 57.16 O ATOM 631 N ARG A 232 170.259 61.057 -8.616 1.00 S N

ANISOU 586 O LEU A 225 5606 6540 9573 -434 694 1274 O ANISOU 631 N ARG A 232 9479 10116 10852 1012 1610 2888 N

ATOM 587 N PRO A 226 185.105 51.424 -2.659 1.00 60.76 N ATOM 632 CA ARG A 232 168.967 60.531 -8.988 1.00 72.26 C

ANISOU 587 N PRO A 226 5980 7135 9972 -354 972 1562 N ANISOU 632 CA ARG A 232 8561 9413 9483 1149 1521 2779 C

ATOM 588 CA PRO A 226 185.086 52.856 -2.996 1.00 62.43 C ATOM 633 CB ARG A 232 169.026 59.020 -8.882 1.00 72.82 C

ANISOU 588 CA PRO A 226 6108 7185 10428 -387 1081 1716 C ANISOU 633 CB ARG A 232 8624 9666 9380 1077 1383 2546 C

ATOM 589 CB PRO A 226 185.830 52.927 -4.326 1.00 60.37 C ATOM 634 CG ARG A 232 168.592 58.275 -10.091 1.00 78.81 C

ANISOU 589 CB PRO A 226 5759 6979 10199 -326 1303 1957 C ANISOU 634 CG ARG A 232 9389 10761 9795 1274 1427 2550 C

ATOM 590 CG PRO A 226 185.745 51.531 -4.897 1.00 59.96 C ATOM 635 CD ARG A 232 168.649 56.800 -9.785 1.00 80.61 C

ANISOU 590 CG PRO A 226 5804 7163 9815 -228 1304 1934 C ANISOU 635 CD ARG A 232 9607 11108 9913 1165 1278 2290 C

ATOM 591 CD PRO A 226 185.750 50.617 -3.706 1.00 61.73 C ATOM 636 NE ARG A 232 167.968 55.961 -10.769 1.00 86.47 N

ANISOU 591 CD PRO A 226 6081 7407 9967 -279 1101 1676 C ANISOU 636 NE ARG A 232 10356 12186 10314 1335 1264 2201 N

ATOM 592 C PRO A 226 183.647 53.319 -3.157 1.00 63.26 C ATOM 637 CZ ARG A 232 166.650 55.912 -10.940 1.00 87.60 C

ANISOU 592 C PRO A 226 6352 7307 10376 -338 1068 1752 C ANISOU 637 CZ ARG A 232 10540 12523 10223 1438 1184 2087 C

ATOM 593 O PRO A 226 182.759 52.576 -3.603 1.00 57.45 O ATOM 638 NHl ARG A 232 165.855 56.672 -10.203 1.00 88.15 N

ANISOU 593 O PRO A 226 5754 6746 9329 -252 1057 1744 O ANISOU 638 NHl ARG A 232 10657 12485 10350 1396 1119 2068 N

ATOM 594 N GLN A 227 183.417 54.557 -2.757 1.00 68.31 N ATOM 639 ΝΉ2 ARG A 232 166.127 55.105 -11.856 1.00 89.07 N

ANISOU 594 N GLN A 227 6948 7759 11246 -395 1065 1775 N ANISOU 639 ΝΉ2 ARG A 232 10709 13016 10117 1591 1164 1978 N

ATOM 595 CA GLN A 227 182.078 55.090 -2.654 1.00 65.90 C

ANISOU 595 CA GLN A 227 6768 7447 10825 -358 1023 1776 C

ATOM 596 CB GLN A 227 182.123 56.367 -1.838 1.00 66.47 C

ANISOU 596 CB GLN A 227 6764 7274 11216 -449 973 1730 C

ATOM 597 CG GLN A 227 182.686 56.144 -0.471 1.00 67.98 C

ANISOU 597 CG GLN A 227 6891 7384 11554 -543 781 1478 C

ATOM 598 CD GLN A 227 183.030 57.434 0.215 1.00 73.56 C

ANISOU 598 CD GLN A 227 7475 7838 12635 -635 747 1424 C

ATOM 599 OE1 GLN A 227 183.237 58.464 -0.433 1.00 75.79 O

ANISOU 599 OE1 GLN A 227 7677 7973 13146 -652 910 1604 O

ATOM 600 NE2 GLN A 227 183.081 57.396 1.538 1.00 75.81 N

ANISOU 600 NE2 GLN A 227 7744 8071 12991 -682 541 1173 N

ATOM 601 C GLN A 227 181.385 55.357 -3.989 1.00 62.96 C

ANISOU 601 C GLN A 227 6463 7185 10274 -233 1196 2004 C

ATOM 602 O GLN A 227 182.012 55.517 -5.059 1.00 56.53 O

ANISOU 602 O GLN A 227 5576 6400 9502 -173 1387 2213 O

ATOM 603 N GLN A 228 180.068 55.424 -3.891 1.00 61.54 N

ANISOU 603 N GLN A 228 6418 7074 9890 -180 1127 1960 N

ATOM 604 CA GLN A 228 179.244 55.806 -5.008 1.00 67.96 C

ANISOU 604 CA GLN A 228 7298 7996 10525 -44 1261 2146 C

ATOM 605 CB GLN A 228 178.360 54.632 -5.427 1.00 72.12 C

ANISOU 605 CB GLN A 228 7950 8787 10667 51 1201 2058 C

ATOM 606 CG GLN A 228 177.754 54.738 -6.824 1.00 74.95 C

ANISOU 606 CG GLN A 228 8353 9331 10792 229 1350 2241 C

ATOM 607 CD GLN A 228 176.840 53.554 -7.134 1.00 74.88 C

ANISOU 607 CD GLN A 228 8448 9574 10427 308 1262 2097 C

ATOM 608 OE1 GLN A 228 176.901 52.518 -6.462 1.00 70.75 O

ANISOU 608 OE1 GLN A 228 7953 9081 9847 230 1130 1897 O

ATOM 609 NE2 GLN A 228 175.985 53.705 -8.146 1.00 75.08 N

ANISOU 609 NE2 GLN A 228 8525 9780 10221 472 1339 2193 N

ATOM 610 C GLN A 228 178.405 56.993 -4.546 1.00 67.50 C

ANISOU 610 C GLN A 228 7280 7791 10577 -58 1232 2161 C

ATOM 611 O GLN A 228 177.930 57.035 -3.397 1.00 67.53 O

ANISOU 611 O GLN A 228 7327 7721 10612 -136 1054 1967 O

ATOM 612 N THR A 229 178.232 57.961 -5.438 1.00 68.06 N

ANISOU 612 N THR A 229 7336 7821 10701 34 1413 2398 N

ATOM 613 CA THR A 229 177.398 59.130 -5.144 1.00 68.55 C

ANISOU 613 CA THR A 229 7443 7748 10855 46 1412 2441 C

ATOM 614 CB THR A 229 178.138 60.437 -5.436 1.00 72.60 C

ANISOU 614 CB THR A 229 7839 8010 11735 23 1598 2651 C

ATOM 615 OG1 THR A 229 179.230 60.581 -4.521 1.00 74.09 O

ANISOU 615 OG1 THR A 229 7897 7992 12261 -146 1522 2512 O

ATOM 616 CG2 THR A 229 177.203 61.616 -5.278 1.00 74.79 C

ANISOU 616 CG2 THR A 229 8179 8161 12077 64 1618 2716 C

ATOM 617 C THR A 229 176.099 59.099 -5.947 1.00 65.14 C

ANISOU 617 C THR A 229 7140 7527 10084 218 1452 2525 C

ATOM 618 O THR A 229 176.119 58.778 -7.138 1.00 59.32 O

ANISOU 618 O THR A 229 6410 6974 9156 362 1594 2684 O

ATOM 619 N GLY A 230 174.981 59.419 -5.289 1.00 68.21 N

ANISOU 619 N GLY A 230 7621 7904 10391 215 1322 2409 N

ATOM 620 CA GLY A 230 173.667 59.369 -5.907 1.00 68.15 C ATOM 665 NZ LYS A 236 169.649 64.836 -10.453 1.00 90.14 N

ANISOU 620 CA GLY A 230 7728 8106 10062 371 1328 2446 C ANISOU 665 NZ LYS A 236 10765 11165 12321 1463 2126 3525 N

ATOM 621 C GLY A 230 173.418 60.605 -6.758 1.00 73.08 C ATOM 666 C LYS A 236 172.033 63.657 -3.966 1.00 61.62 C

ANISOU 621 C GLY A 230 8352 8672 10742 509 1527 2716 C ANISOU 666 C LYS A 236 6971 6568 9874 313 1292 2535 C

ATOM 622 O GLY A 230 173.611 61.736 -6.312 1.00 68.15 O ATOM 667 O LYS A 236 171.682 64.100 -2.859 1.00 60.83 O

ANISOU 622 O GLY A 230 7693 7793 10407 451 1571 2787 O ANISOU 667 O LYS A 236 6892 6323 9897 229 1141 2373 O

ATOM 623 N ASP A 231 173.008 60.387 -8.002 1.00 83.59 N ATOM 668 N ASP A 237 173.309 63.507 -4.339 1.00 62.20 N

ANISOU 623 N ASP A 231 9720 10242 11799 706 1653 2866 N ANISOU 668 N ASP A 237 6930 6558 10146 254 1408 2625 N

ATOM 624 CA ASP A 231 172.624 61.482 -8.893 1.00 92.32 C ATOM 669 CA ASP A 237 174.464 63.799 -3.476 1.00 65.66 C

ANISOU 624 CA ASP A 231 10845 11342 12890 888 1852 3137 C ANISOU 669 CA ASP A 237 7240 6732 10976 73 1361 2523 C

ATOM 625 CB ASP A 231 173.674 61.689 -9.993 1.00103.54 C ATOM 670 CB ASP A 237 174.521 65.290 -3.125 1.00 74.50 C

ANISOU 625 CB ASP A 231 12176 12771 14392 989 2065 3342 C ANISOU 670 CB ASP A 237 8316 7559 12433 41 1419 2574 C

ATOM 626 CG ASP A 231 173.926 60.426 -10.831 1.00109.80 C ATOM 671 CG ASP A 237 174.971 66.159 -4.307 1.00 84.88 C

ANISOU 626 CG ASP A 231 12963 13854 14902 1086 2080 3331 C ANISOU 671 CG ASP A 237 9574 8854 13822 157 1665 2794 C

ATOM 627 OD1 ASP A 231 173.472 59.327 -10.423 1.00110.93 O ATOM 672 OD2 ASP A 237 174.134 66.965 -4.794 1.00 86.07 O

ANISOU 627 OD1 ASP A 231 13153 14155 14841 1028 1912 3123 O ANISOU 672 OD2 ASP A 237 9801 9019 13883 289 1760 2924 O

ATOM 628 OD2 ASP A 231 174.587 60.549 -11.895 1.00112.19 O ATOM 673 OD1 ASP A 237 176.149 66.022 -4.740 1.00 88.75 O

ANISOU 628 OD2 ASP A 231 13210 14225 15192 1227 2227 3464 O ANISOU 673 OD1 ASP A 237 9946 9320 14456 125 1762 2836 O

ATOM 629 C ASP A 231 171.245 61.192 -9.492 1.00 88.71 C ATOM 674 C ASP A 237 174.579 62.945 -2.203 1.00 64.36 C

ANISOU 629 C ASP A 231 10494 11187 12026 1081 1808 3106 C ANISOU 674 C ASP A 237 7076 6593 10786 -58 1103 2208 C

ATOM 630 O ASP A 231 171.078 61.085 -10.704 1.00 91.37 O ATOM 675 O ASP A 237 175.279 63.313 -1.264 1.00 62.37 O

ANISOU 630 O ASP A 231 10840 11747 12131 1296 1947 3265 O ANISOU 675 O ASP A 237 6731 6131 10835 -189 1014 2071 O

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







 ATOM 1216 CA GLN A 306 171.371 39.991 -13.510 1.00 74.70 ATOM 1261 CD1 LEU A 311 166.665 37.238 -3.148 1.00 43.00 C ANISOU 1216 CA GLN A 306 9120 12824 6439 1279 -641 -517 ANISOU 1261 CD1 LEU A 311 5309 5345 5682 4 -1410 -196 C ATOM 1217 CB GLN A 306 171.060 40.120 -15.009 1.00 83.63 ATOM 1262 CD2 LEU A 311 168.652 38.614 -2.408 1.00 36.53 C ANISOU 1217 CB GLN A 306 10194 14604 6977 1402 -700 -472 ANISOU 1262 CD2 LEU A 311 4612 4360 4909 225 -924 -149 C ATOM 1218 CG GLN A 306 170.159 39.016 -15.601 1.00 89.94 ATOM 1263 C LEU A 311 170.442 34.929 -0.897 1.00 43.86 C ANISOU 1218 CG GLN A 306 11074 15559 7538 1376 -1117 -882 ANISOU 1263 C LEU A 311 5921 4486 6259 171 -1428 -970 C ATOM 1219 CD GLN A 306 168.741 38.993 -15.019 1.00 91.37 ATOM 1264 O LEU A 311 170.256 33.767 -1.315 1.00 37.66 O ANISOU 1219 CD GLN A 306 11211 15496 8010 1169 -1387 -705 ANISOU 1264 O LEU A 311 5252 3566 5489 145 -1682 -1213 O ATOM 1220 OE1 GLN A 306 168.349 39.872 -14.244 1.00 90.84 O ATOM 1265 N FLE A 312 170.839 35.201 0.336 1.00 37.83 N ANISOU 1220 OE1 GLN A 306 11053 15185 8277 1104 -1243 -254 ANISOU 1265 N FLE A 312 5161 3549 5664 153 -1309 -832 N ATOM 1221 NE2 GLN A 306 167.973 37.967 -15.381 1.00 91.36 ATOM 1266 CA ILE A 312 171.115 34.122 1.269 1.0043.01 C ANISOU 1221 NE2 GLN A 306 11274 15561 7879 1060 -1780 -1074 ANISOU 1266 CA FLE A 312 5937 3877 6528 126 -1465 -916 C ATOM 1222 C GLN A 306 172.848 39.714 -13.257 1.00 78.44 C ATOM 1267 CB FLE A 312 172.530 34.254 1.828 1.00 48.67 C ANISOU 1222 C GLN A 306 9604 13240 6958 1378 -427 -757 c ANISOU 1267 CB FLE A 312 6657 4574 7260 288 -1343 -1000 C ATOM 1223 O GLN A 306 173.719 40.409 -13.786 1.00 82.44 o ATOM 1268 CGI FLE A 312 173.509 34.573 0.700 1.00 52.31 C ANISOU 1223 O GLN A 306 10002 14080 7242 1461 -138 -557 o ANISOU 1268 CGI FLE A 312 7056 5312 7506 482 -1236 -1203 C ATOM 1224 N ASN A 307 173.101 38.736 -12.388 1.00 75.8 N ATOM 1269 CD1 FLE A 312 174.946 34.652 1.145 1.00 54.27 C ANISOU 1224 N ASN A 307 9388 12494 6947 1359 -565 -1130 N ANISOU 1269 CD1 FLE A 312 7241 5620 7759 636 -1130 -1283 C ATOM 1225 CA ASN A 307 174.433 38.186 -12.151 1.00 74.32 C ATOM 1270 CG2 FLE A 312 172.941 33.002 2.567 1.00 45.06 C ANISOU 1225 CA ASN A 307 9194 12258 6787 1509 -436 -1437 c ANISOU 1270 CG2 FLE A 312 6335 3799 6986 339 -1534 -1105 C ATOM 1226 CB ASN A 307 175.174 38.001 -13.470 1.00 81.17 c ATOM 1271 C FLE A 312 170.066 34.093 2.394 1.00 34.28 C ANISOU 1226 CB ASN A 307 10003 13720 7116 1759 -317 -1637 c ANISOU 1271 C FLE A 312 4810 2616 5601 -81 -1495 -630 C ATOM 1227 CG ASN A 307 175.782 36.638 -13.600 1.00 89.46 c ATOM 1272 O FLE A 312 170.191 34.790 3.396 1.00 37.23 O ANISOU 1227 CG ASN A 307 11186 14716 8089 1999 -448 -2242 c ANISOU 1272 O FLE A 312 5142 2987 6018 -92 -1322 -441 O ATOM 1228 OD1 ASN A 307 176.499 36.179 -12.702 1.00 8) o ATOM 1273 N ALA A 313 169.027 33.298 2.205 1.00 35.64 N ANISOU 1228 OD1 ASN A 307 11055 14235 8272 2055 -415 -2396 ANISOU 1273 N ALA A 313 5001 2687 5855 -257 -1714 -604 N ATOM 1229 ND2 ASN A 307 175.494 35.962 -14.720 1.00 95.35 N ATOM 1274 167.946 33.153 3.187 1.00 40.07 C ANISOU 1229 ND2 ASN A 307 12050 15790 8388 2163 -611 -2605 N ANISOU 1274 CA ALA A 313 5495 3158 6571 -476 -1748 -305 C ATOM 1230 C ASN A 307 175.333 38.936 -11.166 1.00 67.14 C ATOM 1275 CB ALA A 313 166.599 32.963 2.504 1.00 36.67 C ANISOU 1230 C ASN A 307 8170 11138 6202 1425 -164 -1174 C ANISOU 1275 CB ALA A 313 4940 2871 6122 -681 -1903 -210 C ATOM 1231 O ASN A 307 176.548 38.716 -11.142 1.00 71.83 O ATOM 1276 c ALA A 313 168.244 31.939 4.035 1.00 44.56 C ANISOU 1231 O ASN A 307 8675 11863 6754 1559 -5 -1330 O ANISOU 1276 c ALA A 313 6224 3369 7340 -546 -1918 -330 C ATOM 1232 N ASN A 308 174.765 39.826 -10.366 1.00 56.85 N ATOM 1277 0 ALA A 313 168.694 30.915 3.525 1.0047.39 O ANISOU 1232 N ASN A 308 6860 9537 5203 1214 -109 -787 N ANISOU 1277 0 ALA A 313 6712 3617 7676 -475 -2048 -556 O ATOM 1233 CA ASN A 308 175.606 40.594 -9.445 1.00 53.96 C ATOM 1278 N TYR A 314 167.988 32.060 5.328 1.00 45.45 N ANISOU 1233 CA ASN A 308 6416 8969 5119 1094 127 -565 C ANISOU 1278 N TYR A 314 6282 3478 7510 -610 -1796 -51 N ATOM 1234 CB ASN A 308 175.910 41.994 -9.994 1.00 59.55 C ATOM 1279 CA TYR A 314 168.285 30.983 6.261 1.0047.66 C ANISOU 1234 CB ASN A 308 7011 9941 5674 1012 420 -105 C ANISOU 1279 CA TYR A 314 6647 3625 7835 -612 -1836 13 C ATOM 1235 CG ASN A 308 174.704 42.639 -10.584 1.00 61.09 C ATOM 1280 CB TYR A 314 169.755 30.980 6.672 1.00 40.06 C ANISOU 1235 CG ASN A 308 7257 10219 5737 996 376 213 C ANISOU 1280 CB TYR A 314 5761 2650 6809 -368 -1746 -126 C ATOM 1236 OD1 ASN A 308 173.589 42.204 -10.310 1.00 53.33 O ATOM 1281 CG TYR A 314 170.206 32.304 7.203 1.00 36.63 C ANISOU 1236 OD1 ASN A 308 6362 9039 4861 989 140 139 O ANISOU 1281 CG TYR A 314 5247 2377 6292 -290 -1530 -61 C ATOM 1237 ND2 ASN A 308 174.908 43.650 -11.438 1.00 71.64 N ATOM 1282 CD1 TYR A 314 170.550 33.345 6.335 1.00 32.71 C ANISOU 1237 ND2 ASN A 308 8515 11883 6821 995 596 596 N ANISOU 1282 CD1 TYR A 314 4711 1987 5729 -201 -1435 -202 C ATOM 1238 C ASN A 308 175.049 40.689 -8.039 1.00 51.21 C ATOM 1283 CE1 TYR A 314 170.970 34.590 6.849 1.00 34.97 C ANISOU 1238 C ASN A 308 6164 8077 5217 921 38 -481 C ANISOU 1283 CE1 TYR A 314 4954 2379 5953 -155 -1229 -140 C ATOM 1239 O ASN A 308 175.435 41.566 -7.259 1.00 49.27 O ATOM 1284 CZ TYR A 314 171.022 34.767 8.242 1.00 36.24 C ANISOU 1239 O ASN A 308 5892 7634 5193 775 213 -241 O ANISOU 1284 CZ TYR A 314 5122 2551 6098 -194 -1139 28 C ATOM 1240 N CYS A 309 174.164 39.753 -7.715 1.0042.56 N ATOM 1285 OH TYR A 314 171.443 35.969 8.763 1.00 43.14 O ANISOU 1240 N CYS A 309 5184 6749 4238 923 -240 -695 N ANISOU 1285 OH TYR A 314 5986 3525 6882 -168 -943 45 O ATOM 1241 CA CYS A 309 173.419 39.797 -6.488 1.00 44.26 C ATOM 1286 CE2 TYR A 314 170.695 33.737 9.100 1.00 28.94 C ANISOU 1241 CA CYS A 309 5475 6528 4815 771 -329 -583 C ANISOU 1286 CE2 TYR A 314 4227 1547 5222 -263 -1245 165 C ATOM 1242 CB CYS A 309 172.133 40.566 -6.713 1.0048.09 C ATOM 1287 CD2 TYR A 314 170.300 32.523 8.589 1.00 35.45 C ANISOU 1242 CB CYS A 309 5948 7047 5277 706 -337 -246 C ANISOU 1287 CD2 TYR A 314 5084 2255 6128 -314 -1429 136 C ATOM 1243 SG CYS A 309 171.250 40.861 -5.210 1.00 94.69 S ATOM 1288 c TYR A 314 167.415 31.118 7.484 1.00 46.93 C ANISOU 1243 SG CYS A 309 11906 12496 11578 564 -358 -51 S ANISOU 1288 c TYR A 314 6455 3581 7795 -780 -1758 363 C ATOM 1244 C CYS A 309 173.094 38.377 -6.118 1.0046.10 C ATOM 1289 0 TYR A 314 167.003 32.212 7.843 1.00 50.49 O ANISOU 1244 C CYS A 309 5816 6531 5171 787 -620 -933 C ANISOU 1289 0 TYR A 314 6789 4179 8215 -795 -1594 529 O ATOM 1245 O CYS A 309 172.869 37.543 -6.983 1.0047.55 O ATOM 1290 N GLN A 315 167.104 29.993 8.106 1.00 72.93 N ANISOU 1245 O CYS A 309 6050 6873 5145 876 -803 -1201 O ANISOU 1290 N GLN A 315 9353 5038 13321 -1300 -20 237 N ATOM 1246 N ARG A 310 173.060 38.088 -4.825 1.00 37.20 N ATOM 1291 CA GLN A 315 166.370 30.034 9.351 1.00 75.77 C ANISOU 1246 N ARG A 310 4746 5016 4373 690 -672 -934 N ANISOU 1291 CA GLN A 315 9664 5509 13614 -1762 501 463 C ATOM 1247 CA ARG A 310 172.754 36.741 -4.418 1.00 41.58 C ATOM 1292 CB GLN A 315 165.041 29.320 9.196 1.00 77.06 C ANISOU 1247 CA ARG A 310 5424 5299 5077 681 -945 -1209 C ANISOU 1292 CB GLN A 315 9599 5350 14329 -2268 642 439 C ATOM 1248 CB ARG A 310 174.015 35.890 -4.344 1.00 49.83 C ATOM 1293 CG GLN A 315 163.916 29.937 9.984 1.00 80.01 C ANISOU 1248 CB ARG A 310 6514 6291 6127 865 -962 -1535 C ANISOU 1293 CG GLN A 315 9559 6063 14779 -2675 1166 437 C ATOM 1249 CG ARG A 310 173.741 34.397 -4.368 1.00 68.20 C ATOM 1294 CD GLN A 315 162.566 29.411 9.522 1.00 87.78 C ANISOU 1249 CG ARG A 310 9028 8351 8535 917 -1263 -1877 C ANISOU 1294 CD GLN A 315 10152 6953 16248 -3095 1214 249 C ATOM 1250 CD ARG A 310 173.191 33.945 -5.714 1.00 88.72 C ATOM 1295 OE1 GLN A 315 162.462 28.804 8.454 1.00 89.01 O ANISOU 1250 CD ARG A 310 11699 11170 10840 965 -1422 -2111 C ANISOU 1295 OE1 GLN A 315 10277 6914 16631 -3004 820 5 O ATOM 1251 NE ARG A 310 173.214 32.487 -5.889 1.00101.67 N ATOM 1296 NE2 GLN A 315 161.528 29.636 10.320 1.00 91.88 N ANISOU 1251 NE ARG A 310 13571 12532 12527 1052 -1696 -2532 N ANISOU 1296 NE2 GLN A 315 10372 7766 16774 -3495 1667 326 N ATOM 1252 CZ ARG A 310 172.302 31.656 -5.385 1.00105.52 C ATOM 1297 c GLN A 315 167.216 29.388 10.436 1.00 77.20 C ANISOU 1252 CZ ARG A 310 14216 12622 13254 841 -1976 -2573 C ANISOU 1297 c GLN A 315 10394 5661 13279 -1721 605 907 C ATOM 1253 NH1 ARG A 310 172.402 30.347 -5.594 1.00106.99 N ATOM 1298 0 GLN A 315 167.675 28.263 10.282 1.00 74.85 O ANISOU 1253 NH1 ARG A 310 14661 12497 13495 919 -2224 -2968 N ANISOU 1298 0 GLN A 315 10546 4932 12963 -1620 381 1147 O ATOM 1254 NH2 ARG A 310 171.293 32.141 -4.667 1.00105.33 N ATOM 1299 N GLU A 316 167.457 30.132 11.509 1.00 80.87 N ANISOU 1254 NH2 ARG A 310 14093 12507 13420 556 -1998 -2211 N ANISOU 1299 N GLU A 316 10823 6621 13281 -1734 948 991 N ATOM 1255 C ARG A 310 172.080 36.798 -3.082 1.0042.01 C ATOM 1300 CA GLU A 316 168.211 29.620 12.635 1.00 88.80 C ANISOU 1255 C ARG A 310 5509 5006 5448 507 -988 -1013 C ANISOU 1300 CA GLU A 316 12265 7785 13689 -1626 1087 1399 C ATOM 1256 O ARG A 310 172.563 37.443 -2.165 1.00 42.68 O ATOM 1301 CB GLU A 316 168.551 30.746 13.615 1.00 90.73 C ANISOU 1256 O ARG A 310 5565 4976 5675 471 -818 -858 O ANISOU 1301 CB GLU A 316 12319 8744 13408 -1582 1392 1274 C ATOM 1257 N LEU A 311 170.944 36.124 -2.980 1.00 49.64 N ATOM 1302 CG GLU A 316 169.971 31.293 13.482 1.00 92.92 C ANISOU 1257 N LEU A 311 6524 5835 6503 381 -1219 -1020 N ANISOU 1302 CG GLU A 316 12678 9460 13169 -1139 1113 1055 C ATOM 1258 CA LEU A 311 170.134 36.148 -1.765 1.00 44.50 C ATOM 1303 170.120 32.722 13.990 1.00 94.83 C ANISOU 1258 CA LEU A 311 5868 4925 6116 212 -1251 -795 C ANISOU 1303 CD GLU A 316 12575 10300 13158 -1201 1393 655 C ATOM 1259 CB LEU A 311 168.637 36.143 -2.092 1.00 37.98 C ATOM 1304 OE1 GLU A 316 170.648 32.911 15.113 1.00 96.96 O ANISOU 1259 CB LEU A 311 4954 4208 5270 65 -1393 -623 C ANISOU 1304 OE1 GLU A 316 12906 11124 12812 -1159 1597 701 O ATOM 1260 CG LEU A 311 168.190 37.285 -2.987 1.00 43.55 C ATOM 1305 OE2 GLU A 316 169.708 33.650 13.253 1.00 93.08 O ANISOU 1260 CG LEU A 311 5524 5275 5749 139 -1251 -402 C ANISOU 1305 OE2 GLU A 316 12032 9995 13340 -1260 1428 283 O

 ATOM 1396 O GLU A 328 176.229 30.006 2.885 1.00 62.88 O ATOM 1441 N ARG A 334 180.960 29.365 -2.673 1.00 73.05 N ANISOU 1396 O GLU A 328 6186 7300 10406 -736 -619 -431 O ANISOU 1441 N ARG A 334 9408 9770 8576 1503 -1846 -642 N ATOM 1397 N VAL A 329 177.205 31.318 4.376 1.0043.86 N ATOM 1442 CA ARG A 334 181.733 28.398 -3.435 1.00 75.97 C ANISOU 1397 N VAL A 329 3734 5127 7803 -369 -40 32 N ANISOU 1442 CA ARG A 334 10320 10181 8364 1898 -2009 -864 C ATOM 1398 CA VAL A 329 177.678 32.222 3.329 1.00 44.46 C ATOM 1443 CB ARG A 334 182.038 27.177 -2.573 1.00 74.03 C ANISOU 1398 CA VAL A 329 3817 5492 7583 -66 -385 60 C ANISOU 1443 CB ARG A 334 10510 9329 8288 1632 -1740 -1052 C ATOM 1399 CB VAL A 329 178.251 33.510 3.940 1.0041.13 c ATOM 1444 CG ARG A 334 183.164 27.415 -1.606 1.00 69.26 C ANISOU 1399 CB VAL A 329 3243 5257 7129 225 -239 327 c ANISOU 1444 CG ARG A 334 10095 8676 7544 1716 -1187 -555 C ATOM 1400 CGI VAL A 329 178.903 34.399 2.878 1.00 40.20 c ATOM 1445 CD ARG A 334 182.987 26.586 -0.365 1.00 72.23 C ANISOU 1400 CGI VAL A 329 3114 5396 6763 549 -556 495 c ANISOU 1445 CD ARG A 334 10611 8461 8373 1269 -828 -629 C ATOM 1401 CG2 VAL A 329 177.118 34.256 4.615 1.00 38.47 c ATOM 1446 NE ARG A 334 184.094 26.758 0.571 1.00 73.01 N ANISOU 1401 CG2 VAL A 329 2370 5015 7233 104 -195 307 c ANISOU 1446 NE ARG A 334 10908 8547 8285 1394 -319 -195 N ATOM 1402 C VAL A 329 178.664 31.523 2.396 1.00 44.09 c ATOM 1447 CZ ARG A 334 184.043 26.420 1.858 1.00 73.65 C ANISOU 1402 C VAL A 329 4284 5414 7053 136 -544 -3 c ANISOU 1447 CZ ARG A 334 10993 8274 8717 1083 105 -82 C ATOM 1403 O VAL A 329 178.602 31.652 1.176 1.0045.57 o ATOM 1448 NHl ARG A 334 182.924 25.900 2.353 1.00 78.15 N ANISOU 1403 O VAL A 329 4469 5817 7029 287 -939 -112 o ANISOU 1448 NHl ARG A 334 11344 8474 9874 617 107 -302 N ATOM 1404 N LEU A 330 179.560 30.749 2.986 1.00 41.98 N ATOM 1449 ΝΉ2 ARG A 334 185.100 26.605 2.649 1.00 65.04 N ANISOU 1404 N LEU A 330 4453 4920 6576 185 -226 69 N ANISOU 1449 ΝΉ2 ARG A 334 10085 7233 7395 1260 521 283 N ATOM 1405 CA LEU A 330 180.551 30.025 2.206 1.00 39.11 c ATOM 1450 C ARG A 334 181.047 27.948 -4.711 1.00 86.29 C ANISOU 1405 CA LEU A 330 4609 4532 5721 428 -331 18 c ANISOU 1450 C ARG A 334 11630 11684 9473 2084 -2617 -1395 C ATOM 1406 CB LEU A 330 181.568 29.369 3.131 1.00 39.36 c ATOM 1451 O ARG A 334 180.798 26.752 -4.857 1.00 91.93 O ANISOU 1406 CB LEU A 330 5059 4332 5565 495 112 181 c ANISOU 1451 O ARG A 334 12665 12003 10261 1969 -2851 -1926 O ATOM 1407 CG LEU A 330 182.552 30.327 3.780 1.00 43.39 c ATOM 1452 N GLN A 335 180.747 28.912 -5.600 1.00 87.58 N ANISOU 1407 CG LEU A 330 5555 5036 5894 776 365 547 c ANISOU 1452 N GLN A 335 11417 12438 9423 2384 -2886 -1246 N ATOM 1408 CD1 LEU A 330 183.276 29.646 4.980 1.00 44.13 c ATOM 1453 CA GLN A 335 180.170 28.742 -6.954 1.00 87.87 C ANISOU 1408 CD1 LEU A 330 5966 4901 5902 776 848 673 c ANISOU 1453 CA GLN A 335 11383 12860 9144 2706 -3459 -1670 C ATOM 1409 CD2 LEU A 330 183.560 30.791 2.726 1.00 37.18 c ATOM 1454 CB GLN A 335 179.095 27.665 -7.022 1.00 90.28 C ANISOU 1409 CD2 LEU A 330 4938 4549 4640 1187 141 746 c ANISOU 1454 CB GLN A 335 11747 12685 9872 2310 -3914 -2446 C ATOM 1410 C LEU A 330 179.923 28.976 1.294 1.00 45.41 c ATOM 1455 CG GLN A 335 177.881 28.007 -6.206 1.00 88.26 C ANISOU 1410 C LEU A 330 5542 5158 6555 272 -700 -398 c ANISOU 1455 CG GLN A 335 10979 12076 10480 1596 -3838 -2450 C ATOM 1411 O LEU A 330 180.461 28.656 0.225 1.00 44.05 o ATOM 1456 CD GLN A 335 177.590 26.982 -5.121 1.00 91.28 C ANISOU 1411 O LEU A 330 5679 5130 5929 579 -988 -536 o ANISOU 1456 CD GLN A 335 11521 11658 11502 995 -3630 -2652 C ATOM 1412 N ARG A 331 178.806 28.413 1.740 1.00 43.86 N ATOM 1457 OE1 GLN A 335 176.433 26.764 -4.768 1.00 96.56 O ANISOU 1412 N ARG A 331 5103 4655 6908 -174 -703 -592 N ANISOU 1457 OE1 GLN A 335 11834 11989 12866 456 -3773 -2872 O ATOM 1413 CA ARG A 331 178.094 27.424 0.946 1.00 50.07 c ATOM 1458 NE2 GLN A 335 178.632 26.343 -4.595 1.00 90.37 N ANISOU 1413 CA ARG A 331 5945 5189 7890 -384 -1128 -1031 c ANISOU 1458 NE2 GLN A 335 11906 11258 11170 1100 -3279 -2525 N ATOM 1414 CB ARG A 331 176.869 26.912 1.698 1.00 55.85 c ATOM 1459 C GLN A 335 179.538 30.052 -7.398 1.00 83.01 C ANISOU 1414 CB ARG A 331 6289 5554 9378 -931 -1041 -1082 c ANISOU 1459 C GLN A 335 10183 12615 8741 2623 -3360 -1298 C ATOM 1415 CG ARG A 331 176.263 25.621 1.161 1.00 63.99 c ATOM 1460 O GLN A 335 180.012 30.697 -8.325 1.00 82.36 O ANISOU 1415 CG ARG A 331 7417 6109 10788 -1233 -1435 -1508 ANISOU 1460 O GLN A 335 10049 12888 8354 2898 -3109 -926 O ATOM 1416 CD ARG A 331 174.723 25.600 1.377 1.00104.65 TER 1461 GLN A 335

ANISOU 1416 CD ARG A 331 11926 11117 16720 -1742 -1597 -1561 ATOM 1461 N SER B 154 148.849 45.994 3.869 1.00 61.24 N ATOM 1417 NE ARG A 331 174.344 26.087 2.704 1.00102.73 ANISOU 1461 N SER B 154 7667 7421 8180 -452 -1039 158 N ANISOU 1417 NE ARG A 331 11283 10943 16807 -1927 -1033 -1085 ATOM 1462 CA SER B 154 148.821 46.818 2.655 1.00 62.18 C ATOM 1418 CZ ARG A 331 173.970 25.311 3.715 1.00106.52 ANISOU 1462 CA SERB 154 7904 7529 8192 -597 -1236 209 C ANISOU 1418 CZ ARG A 331 11610 11039 17824 -2268 -673 -843 ATOM 1463 CB SER B 154 147.769 47.936 2.754 1.00 63.13 C ATOM 1419 NHl ARG A 331 173.884 23.996 3.547 1.00113.86 ANISOU 1463 CB SER B 154 7769 7644 8574 -584 -1380 415 C ANISOU 1419 NHl ARG A 331 12731 11387 19143 -2540 -848 -1027 ATOM 1464 OG SER B 154 148.239 48.999 3.570 1.00 57.09 O ATOM 1420 ΝΉ2 ARG A 331 173.668 25.855 4.890 1.00103.69 ANISOU 1464 OG SER B 154 6881 6936 7874 -386 -1183 383 O ANISOU 1420 ΝΉ2 ARG A 331 10882 10887 17629 -2298 -155 -405 ATOM 1465 C SER B 154 150.192 47.452 2.385 1.00 54.84 C ATOM 1421 C ARG A 331 177.676 28.051 -0.379 1.00 53.80 C ANISOU 1465 C SER B 154 7135 6654 7046 -528 -1086 66 C ANISOU 1421 C ARG A 331 6218 6073 8151 ■175 -1671 -1246 C ATOM 1466 O SER B 154 151.064 47.518 3.277 1.0047.88 O ATOM 1422 O ARG A 331 177.869 27.476 -1.443 1.00 60.61 O ANISOU 1466 O SER B 154 6204 5830 6158 -355 -859 -33 O ANISOU 1422 O ARG A 331 7366 6973 8691 45 -2082 -1588 o ATOM 1467 N VAL B 155 150.353 47.963 1.158 1.00 43.13 N ATOM 1423 N HIS A 332 177.108 29.252 -0.305 1.00 51.62 N ANISOU 1467 N VAL B 155 5842 5145 5400 -675 -1231 78 N ANISOU 1423 N HIS A 332 5445 6134 8035 -189 -1676 -1046 N ATOM 1468 CA VAL B 155 151.638 48.468 0.734 1.00 32.52 C ATOM 1424 CA HIS A 332 176.729 29.995 -1.501 1.00 54.98 C ANISOU 1468 CA VAL B 155 4671 3826 3857 -631 -1084 -44 C ANISOU 1424 CA HIS A 332 5619 7018 8254 51 -2133 -1145 c ATOM 1469 CB VAL B 155 151.657 48.752 -0.776 1.00 43.29 C ATOM 1425 CB HIS A 332 175.819 31.179 -1.134 1.00 53.62 c ANISOU 1469 CB VAL B 155 6320 5124 5005 -841 -1255 -26 C ANISOU 1425 CB HIS A 332 4825 7066 8481 -107 -2089 -941 c ATOM 1470 CGI VAL B 155 152.878 49.611 -1.148 1.00 38.57 C ATOM 1426 CG HIS A 332 174.473 30.767 -0.661 1.00 60.75 c ANISOU 1470 CGI VAL B 155 5836 4552 4268 -766 -1095 -113 C ANISOU 1426 CG HIS A 332 5343 7712 10028 -618 -2136 -1138 c ATOM 1471 CG2 VAL B 155 151.663 47.430 -1.548 1.00 46.08 C ATOM 1427 NDl HIS A 332 174.263 30.160 0.578 1.00 62.39 N ANISOU 1471 CG2 VAL B 155 6997 5361 5151 -1027 -1278 -96 C ANISOU 1427 NDl HIS A 332 5535 7520 10649 -967 -1728 -1037 ATOM 1472 C VAL B 155 151.991 49.711 1.508 1.00 31.39 C ATOM 1428 CE1 HIS A 332 172.994 29.878 0.719 1.00 68.23 ANISOU 1472 C VAL B 155 4323 3769 3837 -453 -984 -30 C ANISOU 1428 CE1 HIS A 332 5841 8126 11958 -1374 -1863 -1164 ATOM 1473 O VAL B 155 153.060 49.824 2.066 1.00 38.82 O ATOM 1429 NE2 HIS A 332 172.343 30.257 -0.382 1.00 65.54 ANISOU 1473 O VAL B 155 5261 4752 4736 -322 -782 -131 O ANISOU 1429 NE2 HIS A 332 5248 8062 11593 -1326 -2374 -1405 ATOM 1474 N ALA B 156 151.078 50.666 1.529 1.00 35.88 N ATOM 1430 CD2 HIS A 332 173.253 30.802 -1.252 1.00 60.87 ANISOU 1474 N ALA B 156 4718 4345 4572 -459 -1130 115 N ANISOU 1430 CD2 HIS A 332 4939 7820 10368 -837 -2540 -1391 ATOM 1475 CA ALA B 156 151.347 51.956 2.147 1.00 32.65 C ATOM 1431 C HIS A 332 177.951 30.493 -2.263 1.00 53.44 C ANISOU 1475 CA ALA B 156 4157 3986 4264 -313 -1030 131 C ANISOU 1431 C HIS A 332 5707 7231 7365 636 -2172 -912 C ATOM 1476 CB ALA B 156 150.141 52.858 1.981 1.00 34.00 C ATOM 1432 O HIS A 332 178.017 30.405 -3.486 1.00 57.61 O ANISOU 1476 CB ALA B 156 4142 4123 4654 -345 -1194 330 C ANISOU 1432 O HIS A 332 6320 8084 7486 972 -2580 -1097 o ATOM 1477 C ALA B 156 151.690 51.793 3.637 1.00 32.13 C ATOM 1433 N LEU A 333 178.901 31.045 -1.529 1.00 48.63 N ANISOU 1477 C ALA B 156 3964 3956 4288 -132 -809 61 C ANISOU 1433 N LEU A 333 5199 6643 6634 788 -1757 -479 N ATOM 1478 O ALA B 156 152.512 52.502 4.215 1.00 34.92 O ATOM 1434 CA LEU A 333 180.111 31.573 -2.134 1.00 60.37 C ANISOU 1478 O ALA B 156 4308 4350 4608 -25 -673 -6 O ANISOU 1434 CA LEU A 333 6877 8502 7559 1316 -1744 -125 c ATOM 1479 N HIS B 157 151.045 50.848 4.264 1.00 32.63 N ATOM 1435 CB LEU A 333 181.116 32.001 -1.070 1.00 58.85 c ANISOU 1479 N HIS B 157 3946 3994 4458 -115 -789 88 N ANISOU 1435 CB LEU A 333 6795 8181 7383 1368 -1281 297 c ATOM 1480 CA HIS I 157 151.190 50.694 5.704 1.00 35.60 C ATOM 1436 CG LEU A 333 181.275 33.510 -0.922 1.00 64.22 c ANISOU 1480 CA HIS B 157 4224 4387 4916 39 -597 47 C ANISOU 1436 CG LEU A 333 7041 9112 8249 1515 -1250 740 c ATOM 1481 CB HIS I ! 157 150.170 49.654 6.196 1.00 34.17 C ATOM 1437 CD1 LEU A 333 182.617 33.828 -0.281 1.00 64.06 c ANISOU 1481 CB HIS B 157 3939 4155 4890 35 -605 117 C ANISOU 1437 CD1 LEU A 333 7333 8883 8124 1507 -866 1003 c ATOM 1482 CG HIS I 157 150.342 49.250 7.607 1.00 34.58 C ATOM 1438 CD2 LEU A 333 181.168 34.209 -2.264 1.00 66.79 c ANISOU 1482 CG HIS B 157 3943 4212 4983 172 -406 69 C ANISOU 1438 CD2 LEU A 333 7275 9654 8448 1576 -1472 812 c ATOM 1483 NDl HIS B 157 150.119 50.116 8.665 1.00 34.37 N ATOM 1439 C LEU A 333 80.789 30.609 -3.097 1.00 69.76 ANISOU 1483 NDl HIS B 157 3843 4160 5056 291 -260 100 N ANISOU 1439 C LEU A 333 8563 9799 8144 1681 -1954 -338 C ATOM 1484 CE1 HIS B 157 150.339 49.496 9.808 1.00 33.86 C ATOM 1440 O LEU A 333 181.145 30.986 -4.206 1.00 75.74 O ANISOU 1484 CE1 HIS B 157 3802 4094 4971 374 -110 49 C ANISOU 1440 O LEU A 333 9301 11052 8424 2158 -2209 -212 O ATOM 1485 NE2 HIS B 157 150.709 48.246 9.541 1.00 34.91 N



 ANISOU 1665 N ILE B 179 7173 5408 5643 -1433 -1653 -32 N ANISOU 1710 O ASN B 183 10654 6715 7649 -2497 -1907 -253 O ATOM 1666 CA ILE B 179 170.261 73.280 12.429 1.00 51.34 C ATOM 1711 N GLN B 184 174.032 79.142 14.299 1.00 73.30 N ANISOU 1666 CA ILE B 179 7726 5749 6033 -1385 -1457 -155 C ANISOU 1711 N GLN B 184 11379 7858 8612 -2580 -2307 -12 N ATOM 1667 CB ILE B 179 168.746 73.208 12.200 1.00 49.51 C ATOM 1712 CA GLN B 184 174.948 79.884 15.138 1.00 82.13 C ANISOU 1667 CB ILE B 179 7591 5513 5706 -1178 -1137 -309 C ANISOU 1712 CA GLN B 184 12671 8898 9636 -2810 -2535 101 C ATOM 1668 CGI ILE B 179 168.443 72.253 11.047 1.00 45.65 C ATOM 1713 CB GLN B 184 175.150 79.186 16.482 1.00 91.25 C ANISOU 1668 CGI ILE B 179 6765 5178 5401 -943 -1018 -265 C ANISOU 1713 CB GLN B 184 14043 10061 10565 -2947 -2729 196 C ATOM 1669 CD1 ILE B 179 166.948 71.995 10.853 1.00 44.85 C ATOM 1714 CG GLN B 184 174.084 79.545 17.531 1.00101.96 C ANISOU 1669 CD1 ILE B 179 6718 5080 5241 -760 -762 -371 C ANISOU 1714 CG GLN B 184 15942 11286 11513 -2986 -2506 1 C ATOM 1670 CG2 ILE B 179 168.166 74.586 11.903 1.00 45.73 C ATOM 1715 CD GLN B 184 172.658 79.754 16.965 1.00106.22 C ANISOU 1670 CG2 ILE B 179 7273 4909 5192 -1151 -936 -413 C ANISOU 1715 CD GLN B 184 16583 11780 11998 -2761 -2074 -251 C ATOM 1671 C ILE B 179 170.665 74.442 13.365 1.00 60.56 C ATOM 1716 OE1 GLN B 184 172.368 80.749 16.285 1.00109.16 O ANISOU 1671 C ILE B 179 9242 6746 7022 -1657 -1608 -191 C ANISOU 1716 OE1 GLN B 184 16971 12068 12436 -2702 -1879 -359 O ATOM 1672 O ILE B 179 171.000 75.563 12.906 1.00 58.94 O ATOM 1717 NE2 GLN B 184 171.761 78.821 17.278 1.00105.45 N ANISOU 1672 O ILE B 179 9041 6468 6884 -1702 -1587 -199 o ANISOU 1717 NE2 GLN B 184 16554 11721 11792 -2635 -1920 -328 N ATOM 1673 N ARG B 180 170.686 74.164 14.669 1.00 66.48 N ATOM 1718 C GLN B 184 176.256 80.101 14.418 1.00 80.15 C ANISOU 1673 N ARG B 180 10304 7422 7535 -1858 -1771 -205 N ANISOU 1718 C GLN B 184 12019 8692 9741 -2864 -2761 324 C ATOM 1674 CA ARG B 180 171.163 75.166 15.637 1.00 69.06 C ATOM 1719 O GLN B 184 176.783 81.207 14.375 1.00 82.41 O ANISOU 1674 CA ARG B 180 11026 7567 7647 -2172 -1961 -228 C ANISOU 1719 O GLN B 184 12376 8884 10051 -2981 -2817 348 O ATOM 1675 CB ARG B 180 170.896 74.746 17.062 1.00 75.44 C ATOM 1720 N HIS B 185 176.786 79.066 13.828 1.00 75.86 N ANISOU 1675 CB ARG B 180 12178 8320 8168 -2281 -1995 -234 C ANISOU 1720 N HIS B 185 11044 8282 9496 -2762 -2859 497 ATOM 1676 CG ARG I i 180 169.562 74.122 17.178 1.00 82.90 C ATOM 1721 CA HIS I i 185 178.049 79.195 13.178 1.00 74.68 ANISOU 1676 CG ARG B 180 13252 9258 8989 -2104 -1706 -391 C ANISOU 1721 CA HIS 185 10473 8162 9739 -2777 -3022 748 ATOM 1677 CD ARG I i 180 168.622 74.866 18.089 1.00 91.41 C ATOM 1722 CB HIS I ! 185 178.551 77.841 12.772 1.00 77.52 ANISOU 1677 CD ARG B 180 14795 10145 9790 -2119 -1413 -532 C ANISOU 1722 CB HIS 10412 8651 10392 -2650 -3082 950 ATOM 1678 NE ARG I i 180 169.129 74.968 19.456 1.00100.91 N ATOM 1723 CG HIS I 179.149 77.080 13.899 1.00 88.03 ANISOU 1678 NE ARG B 180 16315 11264 10761 -2343 -1573 -441 N ANISOU 1723 CG HIS B 185 11789 9999 11660 -2778 -3359 1147 ATOM 1679 CZ ARG I i 180 169.443 73.937 20.246 1.00103.16 C ATOM 1724 NDl HIS B 185 179.135 77.551 15.190 1.00 93.29 N ANISOU 1679 CZ ARG B 180 16615 11608 10973 -2421 -1766 -325 C ANISOU 1724 NDl HIS 3 185 12851 10573 12022 -3002 -3550 1147 ATOM 1680 NH1 ARG B 180 169.887 74.169 21.481 1.00106.20 N ATOM 1725 CE1 HIS I 185 179.719 76.676 15.980 1.00 97.67 C ANISOU 1680 NH1 ARG B 180 17341 11878 11131 -2650 -1909 -236 ] ANISOU 1725 CE1 HIS : i 185 13359 11147 12602 -3089 -3788 1370 ATOM 1681 NH2 ARG B 180 169.322 72.682 19.815 1.00 98.28 N ATOM 1726 NE2 HIS I 185 180.104 75.650 15.246 1.00 97.08 N ANISOU 1681 NH2 ARG B 180 15690 11149 10501 -2284 -1818 -288 ] ANISOU 1726 NE2 HB i 185 12864 11175 12849 -2910 -3731 1501 ATOM 1682 C ARG B 180 172.637 75.428 15.462 1.00 60.80 C ATOM 1727 CD2 HIS I 185 179.769 75.883 13.940 1.00 90.14 C ANISOU 1682 C ARG B 180 9743 6551 6807 -2339 -2292 -15 C ANISOU 1727 CD2 HIS i 185 11758 10345 12146 -2712 -3458 1366 ATOM 1683 O ARG B 180 173.079 76.566 15.548 1.00 57.56 O ATOM 1728 C HIS 185 178.042 80.071 11.976 1.00 72.41 C ANISOU 1683 O ARG B 180 9460 6038 6372 -2462 -2329 -10 O ANISOU 1728 C HIS I ! 185 10028 7824 9659 -2694 -2837 688 C ATOM 1684 N THR B 181 173.391 74.373 15.189 1.00 57.39 N ATOM 1729 O HIS B 185 179.011 80.716 11.674 1.00 80.31 O ANISOU 1684 N THR B 181 8938 6255 6611 -2315 -2492 181 N ANISOU 1729 O HIS I i 185 10906 8768 10839 -2781 -2944 820 O ATOM 1685 CA THR B 181 174.795 74.556 14.870 1.00 59.91 C ATOM 1730 N TYR ] i 186 176.943 80.076 11.274 1.00 72.02 N ANISOU 1685 CA THR B 181 8944 6598 7222 -2411 -2738 428 C ANISOU 1730 N TYR B 186 9985 7808 9570 -2478 -2519 501 N ATOM 1686 CB THR B 181 175.523 73.230 14.599 1.00 66.32 C ATOM 1731 CA TYR B 186 176.873 80.634 9.954 1.00 71.52 C ANISOU 1686 CB THR B 181 9331 7539 8330 -2337 -2878 662 C ANISOU 1731 CA TYR B 186 9724 7758 9693 -2262 -2234 471 C ATOM 1687 OG1 THR B 181 175.603 72.481 15.816 1.00 73.88 O ATOM 1732 CB TYR B 186 176.359 79.551 9.030 1.00 75.47 C ANISOU 1687 OG1 THR B 181 10457 8499 9114 -2430 -3025 745 O ANISOU 1732 CB TYR B 186 9949 8416 10312 -1926 -1955 465 C ATOM 1688 CG2 THR B 181 176.947 73.498 14.086 1.00 62.18 C ATOM 1733 CG TYR B 186 177.374 78.926 8.142 1.00 84.72 C ANISOU 1688 CG2 THR B 181 8440 7006 8180 -2390 -3049 935 C ANISOU 1733 CG TYR B 186 10677 9649 11864 -1849 -1995 710 C ATOM 1689 C THR B 181 174.908 75.477 13.669 1.00 52.36 C ATOM 1734 CD2 TYR B 186 177.670 79.485 6.930 1.00 88.16 C ANISOU 1689 C THR B 181 7812 5615 6469 -2333 -2603 386 C ANISOU 1734 CD2 TYR B 186 10885 10073 12540 -1701 -1792 772 ATOM 1690 O THR B 181 175.606 76.470 13.708 1.00 57.02 O ATOM 1735 CE2 TYR B 186 178.587 78.916 6.089 1.00 92.39 C ANISOU 1690 O THR B 181 8440 6117 7108 -2479 -2720 449 O ANISOU 1735 CE2 TYR B 186 11040 10625 13438 -1615 -1759 1001 ATOM 1691 N TYR B 182 174.187 75.161 12.606 1.00 51.70 N ATOM 1736 CZ TYR B 186 179.205 77.766 6.452 1.00 96.59 C ANISOU 1691 N TYR B 182 7527 5630 6486 -2013 -2259 296 N ANISOU 1736 CZ TYR B 186 11380 11191 14130 -1673 -1939 1188 ATOM 1692 CA TYR B 182 174.224 75.977 11.396 1.00 50.09 C ATOM 1737 OH TYR B 186 180.111 77.224 5.594 1.00102.22 O ANISOU 1692 CA TYR B 182 7150 5422 6460 -1864 -2051 272 C ANISOU 1737 OH TYR B 186 11706 11885 15248 -1572 -1849 1436 ATOM 1693 CB TYR B 182 173.351 75.356 10.309 1.00 46.79 C ATOM 1738 CE1 TYR B 186 178.928 77.178 7.648 1.00 93.23 C ANISOU 1693 CB TYR B 182 6547 5122 6109 -1538 -1719 192 C ANISOU 1738 CE1 TYR B 186 11154 10796 13473 -1827 -2182 1141 ATOM 1694 CG TYR B 182 173.556 75.997 8.969 1.00 50.20 C ATOM 1739 CD1 TYR B 186 178.007 77.756 8.488 1.00 89.24 C ANISOU 1694 CG TYR B 182 6769 5562 6744 -1392 -1539 215 C ANISOU 1739 CD1 TYR B 186 11064 10271 12572 -1917 -2205 895 ATOM 1695 CD1 TYR B 182 172.789 77.099 8.588 1.00 53.00 C ATOM 1740 C TYR B 186 175.902 81.785 9.931 1.00 64.14 C ANISOU 1695 CD1 TYR B 182 7291 5850 6996 -1329 -1341 69 C ANISOU 1740 C TYR B 186 9138 6710 8523 -2247 -2010 241 C ATOM 1696 CE1 TYR B 182 172.979 77.721 7.373 1.00 54.48 C ATOM 1741 O TYR B 186 175.281 82.029 8.942 1.00 61.93 O ANISOU 1696 CE1 TYR B 182 7308 6040 7353 -1209 -1189 100 C ANISOU 1741 O TYR B 186 8761 6463 8307 -2009 -1705 164 o ATOM 1697 CZ TYR B 182 173.945 77.240 6.508 1.00 55.96 C ATOM 1742 N ASN B 187 175.763 82.478 11.039 1.00 62.32 N ANISOU 1697 CZ TYR B 182 7175 6281 7808 -1145 -1200 268 C ANISOU 1742 N ASN B 187 9334 6328 8017 -2511 -2154 143 N ATOM 1698 OH TYR B 182 174.075 77.899 5.296 1.00 58.47 O ATOM 1743 CA ASN ] i 187 174.815 83.559 11.123 1.00 67.81 C ANISOU 1698 OH TYR B 182 7372 6583 8261 -1027 -1022 289 O ANISOU 1743 CA ASN 187 10402 6871 8490 -2510 -1905 -71 ATOM 1699 CE2 TYR B 182 174.740 76.135 6.863 1.00 51.93 C ATOM 1744 CB ASN ] ! 187 174.679 83.976 12.561 1.00 78.04 ANISOU 1699 CE2 TYR B 182 6479 5818 7433 -1194 -1362 422 C ANISOU 1744 CB ASN 187 12167 8034 9453 -2770 -2046 -140 ATOM 1700 CD2 TYR B 182 174.536 75.527 8.093 1.00 51.75 C ATOM 1745 CG ASN ] i 187 173.505 84.876 12.787 1.00 84.41 ANISOU 1700 CD2 TYR B 182 6608 5807 7246 -1320 -1547 399 C ANISOU 1745 CG ASN ] 187 13399 8677 9997 -2718 -1697 -373 ATOM 1701 C TYR B 182 173.771 77.415 11.657 1.00 52.92 C ATOM 1746 OD1 ASN ] 187 172.619 85.002 11.948 1.00 86.04 o ANISOU 1701 C TYR B 182 7853 5631 6624 -1967 -1967 111 C ANISOU 1746 OD1 ASN 187 13577 8858 10257 -2505 -1379 -490 O ATOM 1702 O TYR B 182 174.367 78.359 11.136 1.00 51.49 O ATOM 1747 ND2 ASN ] i 187 173.493 85.519 13.926 1.00 85.00 N ANISOU 1702 O TYR B 182 7590 5389 6586 -2020 -1987 160 O ANISOU 1747 ND2 ASN 187 13857 8637 9801 -2892 -1729 -413 N ATOM 1703 N ASN B 183 172.724 77.574 12.468 1.00 54.55 N ATOM 1748 C ASN ] i 187 175.186 84.759 10.276 1.00 68.04 C ANISOU 1703 N ASN B 183 8447 5758 6521 -1992 -1844 -73 N ANISOU 1748 C ASN 187 10310 6831 8711 -2465 -1781 -54 C ATOM 1704 CA ASN 1 i 183 172.195 78.906 12.788 1.00 57.74 C ATOM 1749 O ASN ] i 187 174.344 85.483 9.799 1.00 64.82 O ANISOU 1704 CA ASN 183 9221 5981 6736 -2078 -1698 -233 C ANISOU 1749 O ASN 187 9985 6379 8266 -2283 -1448 -188 O ATOM 1705 CB ASN I ! 183 170.885 78.824 13.580 1.00 55.14 C ATOM 1750 N ASN ] i 188 176.469 84.958 10.090 1.00 69.05 N ANISOU 1705 CB ASN B 183 9274 5559 6116 -2032 -1460 -418 C ANISOU 1750 N ASN I 188 10230 6938 9067 -2638 -2054 133 N ATOM 1706 CG ASN ] i 183 169.674 78.672 12.674 1.00 56.88 C ATOM 1751 CA ASN ] B 188 176.944 86.043 9.271 1.00 71.48 C ANISOU 1706 CG ASN ] 183 9328 5849 6436 -1697 -1085 -499 C ANISOU 1751 CA ASN 188 10403 7177 9579 -2606 -1951 170 C ATOM 1707 OD1 ASN ] 183 169.761 78.933 11.458 1.00 57.99 O ATOM 1752 CB ASN ] ! 188 178.460 86.061 9.288 1.00 76.31 C ANISOU 1707 OD1 ASN 183 9159 6072 6802 -1532 -990 -449 O ANISOU 1752 CB ASN 188 10765 7759 10470 -2829 -2302 419 C ATOM 1708 ND2 ASN ] i 183 168.535 78.247 13.251 1.00 50.75 N ATOM 1753 CG ASN ] i 188 179.009 86.591 10.567 1.00 83.08 C ANISOU 1708 ND2 ASN 183 8757 5027 5497 -1607 -877 -606 N ANISOU 1753 CG ASN ] 188 11918 8568 11082 -3066 -2548 430 C ATOM 1709 C ASN i 183 173.179 79.783 13.522 1.00 65.45 C ATOM 1754 OD1 ASN ] 188 178.295 87.161 11.355 1.00 89.66 O ANISOU 1709 C ASN B 183 10428 6806 7635 -2424 -1996 -178 C ANISOU 1754 OD1 ASN 188 13199 9292 11574 -3143 -2440 232 O ATOM 1710 O ASN B 183 173.167 81.008 13.404 1.00 65.84 O ATOM 1755 ND2 ASN ] i 188 180.276 86.390 10.786 1.00 82.66 N ANISOU 1755 ND2 ASN B 1 11627 8574 11206 -3179 -2865 685 N ANISOU 1800 O VAL B 194 8028 4902 5535 -992 -272 -639 O ATOM 1756 C ASN B 188 176470 85.965 7.843 1.00 66.95 C ATOM 1801 N SER B 195 164.443 77.521 9.840 1.0042.07 N ANISOU 1756 C ASN B 188 9517 6728 9194 -2239 -1602 166 C ANISOU 1801 N SER B 195 6867 4165 4952 -617 57 -597 N ATOM 1757 O ASN ] i 188 176.148 86.962 7.261 1.00 67.49 O ATOM 1802 CA SER B 195 163.552 76.840 10.766 1.00 52.48 C ANISOU 1757 O ASN B 188 9636 6725 9283 -2144 -1375 90 O ANISOU 1802 CA SERB 195 8347 5429 6166 -586 176 -647 C ATOM 1758 N LEU I i 189 176.465 84.771 7.285 1.00 61.56 N ATOM 1803 CB SER B 195 162.170 76.712 10.131 1.00 60.75 C ANISOU 1758 N LEU B 189 8531 6217 8640 -2049 -1569 257 N ANISOU 1803 CB SER B 195 9230 6474 7379 -367 412 -601 C ATOM 1759 CA LEU B 189 176.128 84.548 5.895 1.00 62.09 C ATOM 1804 OG SER B 195 161.732 78.018 9.787 1.00 69.72 O ANISOU 1759 CA LEU B 189 8331 6393 8866 -1742 -1282 276 C ANISOU 1804 OG SER B 195 10413 7460 8618 -321 614 -592 O ATOM 1760 CB LEU B 189 176.511 83.127 5.495 1.00 61.64 C ATOM 1805 C SER B 195 164.064 75.484 11.234 1.00 51.84 C ANISOU 1760 CB LEU B 189 7971 6485 8965 -1617 -1313 410 C ANISOU 1805 C SER B 195 8215 5485 5996 -645 -39 -630 C ATOM 1761 CG LEU B 189 177.470 82.897 4.332 1.00 62.17 C ATOM 1806 O SER B 195 164.925 74.879 10.602 1.00 42.86 O ANISOU 1761 CG LEU B 189 7663 6583 9376 -1500 -1236 606 C ANISOU 1806 O SER B 195 6838 4509 4939 -651 -243 -557 O ATOM 1762 CD1 LEU I ! 189 177.618 81.404 4.133 1.00 62.87 C ATOM 1807 N GLN B 196 163.480 74.987 12.316 1.00 64.16 N ANISOU 1762 CD1 LEU B 189 7543 6788 9555 -1378 -1219 701 C ANISOU 1807 N GLN B ! 196 10002 6966 7410 -672 44 -687 N ATOM 1763 CD2 LEU I ! 189 176.984 83.562 3.060 1.00 57.30 C ATOM 1808 CA GLN I i 196 164.055 73.855 13.039 1.00 72.80 C ANISOU 1763 CD2 LEU B 189 7021 5966 8785 -1294 -929 547 C ANISOU 1808 CA GLN : B 196 11130 8149 8381 -774 -170 -672 C ATOM 1764 C LEU I ! 189 174.634 84.678 5.739 1.00 62.94 C ATOM 1809 CB GLN B ! 196 163.972 74.078 14.546 1.00 80.99 C ANISOU 1764 C LEU B 189 8642 6519 8754 -1557 -1001 82 C ANISOU 1809 CB GLN ] B 196 12621 9001 9149 -951 -138 -757 C ATOM 1765 O LEU I i 189 174.133 85.388 4.861 1.00 61.02 O ATOM 1810 CG GLN I i 196 165.316 74.343 15.193 1.00 95.59 C ANISOU 1765 O LEU B 189 8375 6256 8552 -1405 -768 42 O ANISOU 1810 CG GLN : B 196 14648 10827 10844 -1229 -457 -736 C ATOM 1766 N LEU I i 190 173.946 83.959 6.618 1.00 62.94 N ATOM 1811 CD GLN I i 196 165.674 75.830 15.239 1.00108.14 C ANISOU 1766 N LEU B 190 8826 6548 8542 -1578 -1035 -11 N ANISOU 1811 CD GLN : B 196 16464 12247 12378 -1367 -425 -787 C ATOM 1767 CA LEU B 190 172.509 83.727 6.555 1.00 63.15 C ATOM 1812 OE1 GLN I 3 196 166.392 76.280 16.142 1.00110.78 O ANISOU 1767 CA LEU B 190 8984 6606 8406 -1390 -786 -151 C ANISOU 1812 OE1 GLN B 196 17129 12459 12502 -1637 -608 -808 O ATOM 1768 CB LEU B 190 172.129 82.742 7.643 1.00 67.75 C ATOM 1813 NE2 GLN I 3 196 165.174 76.600 14.260 1.00112.63 N ANISOU 1768 CB LEU B 190 9723 7219 8798 -1457 -889 -206 C ANISOU 1813 NE2 GLN B 196 16864 12799 13132 -1199 -207 -796 N ATOM 1769 CG LEU B 190 171.276 81.566 7.219 1.00 74.45 C ATOM 1814 C GLN B 196 163.509 72.463 12.711 1.00 70.84 C ANISOU 1769 CG LEU B 190 10432 8218 9636 -1232 -759 -221 C ANISOU 1814 C GLN B 196 10643 8054 8219 -618 -163 -628 C ATOM 1770 CD1 LEU B 190 171.050 80.704 8.472 1.00 77.34 C ATOM 1815 O GLN B 196 163.999 71.467 13.245 1.00 76.13 O ANISOU 1770 CD1 LEU B 190 10987 8588 9811 -1340 -886 -269 C ANISOU 1815 O GLN B ! 196 11308 8803 8813 -687 -334 -601 O ATOM 1771 CD2 LEU I 3 190 169.958 82.026 6.591 1.00 73.51 C ATOM 1816 N ARG B 197 162.508 72.374 11.852 1.00 59.95 N ANISOU 1771 CD2 LEU B 190 10355 8081 9496 -1027 -459 -304 C ANISOU 1816 N ARG E ! 197 9069 6708 7002 -424 16 -605 N ATOM 1772 C LEU B 190 171.660 84.976 6.744 1.00 61.83 C ATOM 1817 CA ARG I i 197 161.961 71.056 11.539 1.00 49.55 C ANISOU 1772 C LEU B 190 9091 6274 8126 -1388 -573 -282 C ANISOU 1817 CA ARG B 197 7550 5520 5758 -301 10 -563 C ATOM 1773 O LEU B 190 170.708 85.197 6.003 1.00 56.91 O ATOM 1818 CB ARG B 197 160.438 71.021 11.711 1.00 53.83 C ANISOU 1773 O LEU B 190 8414 5670 7538 -1180 -324 -312 O ANISOU 1818 CB ARG B 197 8120 5962 6373 -163 275 -566 C ATOM 1774 N ARG B 191 172.014 85.788 7.738 1.00 68.47 N ATOM 1819 CG ARG I 3 197 159.874 72.262 12.354 1.00 64.15 C ANISOU 1774 N ARG I i 191 10238 6938 8839 -1634 -674 -342 N ANISOU 1819 CG ARG B 197 9690 7037 7647 -180 523 -615 C ATOM 1775 CA ARG B 191 171.209 86.949 8.119 1.00 74.22 C ATOM 1820 CD ARG I 3 197 158.752 72.003 13.355 1.00 68.99 C ANISOU 1775 CA ARG B 191 11298 7462 9441 -1655 -435 -477 C ANISOU 1820 CD ARG B 197 10495 7485 8232 -122 790 -639 C ATOM 1776 CB ARG B 191 171.350 88.090 7.109 1.00 74.04 C ATOM 1821 NE ARG I i 197 158.929 72.811 14.570 1.00 80.52 N ANISOU 1776 CB ARG B 191 11145 7383 9603 -1573 -288 -438 C ANISOU 1821 NE ARG B 197 12398 8719 9478 -259 934 -738 N ATOM 1777 CG ARG I i 191 172.740 88.712 7.108 1.00 75.92 C ATOM 1822 CZ ARG I i 197 158.862 74.147 14.633 1.00 86.32 C ANISOU 1777 CG ARG B 191 11337 7563 9945 -1796 -533 -353 C ANISOU 1822 CZ ARG B 197 13318 9265 10213 -292 1114 -773 C ATOM 1778 CD ARG I i 191 172.757 90.056 6.420 1.00 79.96 C ATOM 1823 NH1 ARG B 197 159.057 74.768 15.793 1.00 91.37 N ANISOU 1778 CD ARG B 191 11847 7953 10581 -1758 -355 -353 C ANISOU 1823 NH1 ARG B 197 14425 9682 10610 -447 1239 -877 N ATOM 1779 NE ARG I i 191 173.104 91.147 7.335 1.00 89.29 N ATOM 1824 NH2 ARG B 197 158.606 74.869 13.548 1.00 84.76 N ANISOU 1779 NE ARG B 191 13402 8892 11634 -2034 -411 -436 N ANISOU 1824 NH2 ARG B 197 12874 9088 10244 -184 1169 -702 N ATOM 1780 CZ ARG I i 191 172.425 92.291 7.463 1.00 88.21 C ATOM 1825 C ARG B 197 162.345 70.607 10.146 1.0044.78 C ANISOU 1780 CZ ARG B 191 13536 8548 11431 -2024 -136 -546 C ANISOU 1825 C ARG 3 197 6627 5082 5304 -221 -102 -489 C ATOM 1781 NH1 ARG B 191 171.333 92.505 6.733 1.00 88.25 N ATOM 1826 O ARG I ! 197 162.632 71.413 9.264 1.00 48.26 O ANISOU 1781 NH1 ARG B 191 13440 8569 11521 -1741 203 -560 N ANISOU 1826 O ARG B 197 6980 5527 5829 -207 -104 -462 O ATOM 1782 NH2 ARG B 191 172.842 93.220 8.326 1.00 84.38 N ATOM 1827 N LEU I 198 162.348 69.301 9.930 1.0041.67 N ANISOU 1782 NH2 ARG B 191 13431 7823 10804 -2310 -204 -626 N ANISOU 1827 N LEU I 3 198 6087 4812 4935 -172 -178 -456 N ATOM 1783 C ARG B 191 169.759 86.529 8.274 1.00 73.97 C ATOM 1828 CA LEU I 3 198 162.463 68.791 8.575 1.00 41.75 C ANISOU 1783 C ARG B 191 11365 7431 9311 -1460 -161 -567 C ANISOU 1828 CA LEU B 198 5858 4942 5063 -90 -223 -396 C ATOM 1784 O ARG I i 191 168.854 87.141 7.717 1.00 77.21 O ATOM 1829 CB LEU I 3 198 162.963 67.366 8.608 1.00 37.38 C ANISOU 1784 O ARG B 191 11758 7781 9798 -1283 125 -588 O ANISOU 1829 CB LEU B 198 5205 4496 4502 -90 -326 -369 C ATOM 1785 N GLY I ! 192 169.569 85.445 9.018 1.00 70.73 N ATOM 1830 CG LEU B 198 163.005 66.664 7.259 1.00 41.71 C ANISOU 1785 N GLY I B 192 11027 7088 8760 -1493 -263 -592 N ANISOU 1830 CG LEU B 198 5576 5136 5137 -15 -332 -322 C ATOM 1786 CA GLY I B 192 168.259 84.914 9.309 1.00 71.86 C ATOM 1831 CD1 LEU I ! 198 164.036 67.316 6.311 1.00 38.71 C ANISOU 1786 CA GLY i 192 11261 7224 8820 -1331 -28 -662 C ANISOU 1831 CD1 LEU B 198 5126 4766 4818 -41 -365 -280 C ATOM 1787 C GLY B 192 168.454 83.629 10.075 1.00 76.87 C ATOM 1832 CD2 LEU I ! 198 163.310 65.171 7.472 1.00 36.17 C ANISOU 1787 C GLY B 192 11927 7962 9319 -1408 -230 -660 C ANISOU 1832 CD2 LEU B 198 4807 4505 4430 -5 -380 -303 C ATOM 1788 O GLY B 192 169.567 83.326 10.507 1.00 85.87 O ATOM 1833 C LEU ! 198 161.090 68.855 7.879 1.00 44.48 C ANISOU 1788 O GLY B 192 13070 9139 10418 -1612 -542 -607 O ANISOU 1833 C LEU B 198 6124 5271 5505 32 -94 -368 C ATOM 1789 N ALA B 193 167.375 82.875 10.251 1.00 70.09 N ATOM 1834 O LEU B 198 160.102 68.354 8.425 1.00 50.79 O ANISOU 1789 N ALA B 193 11074 7140 8417 -1249 -60 -697 N ANISOU 1834 O LEU B 198 6949 6034 6314 84 -7 -371 O ATOM 1790 CA ALA B 193 167.443 81.577 10.900 1.00 57.93 C ATOM 1835 N TYR B 199 161.014 69.517 6.720 1.00 36.43 N ANISOU 1790 CA ALA B 193 9539 5708 6765 -1288 -220 -690 C ANISOU 1835 N TYR B 199 5009 4262 4570 67 -87 -320 N ATOM 1791 CB ALA B 193 166.814 81.629 12.279 1.00 54.00 C ATOM 1836 CA TYR B 199 159.753 69.591 5.955 1.00 34.46 C ANISOU 1791 CB ALA B 193 9495 5018 6006 -1404 -98 -811 C ANISOU 1836 CA TYR B 199 4660 3998 4435 156 -23 -246 C ATOM 1792 C ALA B 193 166.671 80.625 10.035 1.00 57.55 C ATOM 1837 CB TYR B 199 159.447 71.013 5.497 1.00 33.63 C ANISOU 1792 C ALA B 193 9166 5837 6863 -1025 -113 -636 C ANISOU 1837 CB TYR B 199 4555 3801 4420 175 59 -201 C ATOM 1793 O ALA B 193 165.511 80.879 9.707 1.00 59.23 O ATOM 1838 CG TYR B 199 159.161 71.921 6.666 1.00 42.42 C ANISOU 1793 O ALA B 193 9366 5996 7142 -851 158 -655 O ANISOU 1838 CG TYR B 199 5828 4757 5532 167 225 -249 C ATOM 1794 N VAL B 194 167.298 79.523 9.650 1.00 53.72 N ATOM 1839 CD1 TYR B 199 160.206 72.425 7.464 1.00 43.64 C ANISOU 1794 N VAL B 194 8418 5546 6447 -1004 -323 -551 N ANISOU 1839 CD1 TYR B 199 6160 4867 5555 63 206 -343 C ATOM 1795 CA VAL B 194 166.524 78.480 9.037 1.00 50.37 C ATOM 1840 CE1 TYR B 199 159.948 73.236 8.544 1.00 44.58 C ANISOU 1795 CA VAL B 194 7770 5266 6101 -797 -237 -519 C ANISOU 1840 CE1 TYR B 199 6501 4813 5625 27 367 -401 C ATOM 1796 CB VAL B 194 167.408 77.467 8.283 1.00 47.68 C ATOM 1841 CZ TYR B 199 158.620 73.567 8.857 1.00 46.43 C ANISOU 1796 CB VAL B 194 7119 5115 5880 -765 -427 -412 C ANISOU 1841 CZ TYR B 199 6761 4902 5979 126 606 -359 C ATOM 1797 CGI VAL B 194 168.853 77.887 8.368 1.00 50.34 C ATOM 1842 OH TYR B 199 158.344 74.384 9.954 1.00 48.34 O ANISOU 1797 CGI VAL B 194 7418 5435 6273 -941 -644 -342 C ANISOU 1842 OH TYR B 199 7277 4928 6164 92 833 -423 O ATOM 1798 CG2 VAL B 194 167.199 76.065 8.777 1.00 39.36 C ATOM 1843 CE2 TYR B 199 157.570 73.054 8.093 1.00 44.08 C ANISOU 1798 CG2 VAL B 194 6031 4160 4764 -739 -498 -407 C ANISOU 1843 CE2 TYR B 199 6228 4652 5867 245 625 -238 C ATOM 1799 C VAL B 194 165.680 77.874 10.160 1.00 46.53 C ATOM 1844 CD2 TYR B 199 157.852 72.235 7.010 1.00 42.22 C ANISOU 1799 C VAL B 194 7511 4717 5452 -806 -151 -595 C ANISOU 1844 CD2 TYR B 199 5796 4604 5642 250 409 -188 C ATOM 1800 O VAL B 194 166.131 77.793 11.296 1.0048.60 O ATOM 1845 C TYR B 199 159.683 68.588 4.799 1.00 32.02 C



 7369 7143 9014 -663 -662 465 C ANISOU 2070 C GLN B 228 15252 16449 18937 -290 -3158 553 C 175.629 76.531 2.085 1.00 68.73 O ATOM 2071 O GLN B 228 175.194 61.638 8.192 1.00130.89 O 8054 8015 10048 -570 -549 580 O ANISOU 2071 O GLN B 228 14910 16176 18644 -220 -2851 565 O 175.142 76.020 4.098 1.00 57.53 O ATOM 2072 N THR B 229 176.629 61.324 9.899 1.00138.46 N 6856 6530 8474 -847 -877 495 O ANISOU 2072 N THR B 229 15882 17020 19708 -277 -3362 649 N 172.799 74.100 1.721 1.00 44.61 C ATOM 2073 CA THR B 229 176.977 59.983 9.465 1.00140.17 C 5272 5116 6561 -348 -343 308 C ANISOU 2073 CA THR B 229 15967 17164 20126 -182 -3288 784 C 171.696 73.657 1.810 1.0047.55 O ATOM 2074 CB THR B 229 178.503 59.788 9.416 1.00143.45 C 5767 5551 6750 -305 -340 196 O ANISOU 2074 CB THR B 229 16118 17387 21000 -161 -3374 845 C N i 173.870 73.387 1.981 1.00 44.55 N ATOM 2075 OG1 THR B 229 179.113 60.946 8.829 1.00143.52 O

N I 5084 5086 6756 -374 -375 452 N ANISOU 2075 OG1 THR B 229 15933 17317 21280 -194 -3271 754 O I 173.763 72.106 2.610 1.00 42.31 C ATOM 2076 CG2 THR B 229 178.856 58.561 8.596 1.00142.57 C 4757 4857 6464 -380 -452 474 C ANISOU 2076 CG2 THR B 229 15823 17177 21171 -56 -3188 954 C I 3 174.841 71.190 2.144 1.00 42.88 C ATOM 2077 C THR B 229 176.332 58.964 10.398 1.00140.42 C 4608 4880 6806 -327 -342 656 C ANISOU 2077 C THR B 229 16268 17277 19808 -177 -3442 869 C I 3 174.779 70.883 0.680 1.00 51.87 C ATOM 2078 O THR B 229 176.459 59.057 11.625 1.00143.15 O 5780 5985 7944 -172 -37 641 C ANISOU 2078 O THR B 229 16811 17639 19940 -241 -3706 874 O I 3 173.568 70.056 0.328 1.00 59.96 C ATOM 2079 N GLY B 230 175.631 58.002 9.807 1.00136.83 N 6957 7084 8742 -90 42 510 C ANISOU 2079 N GLY B 230 15832 16864 19294 -104 -3263 936 N 3 173.700 69.459 -1.053 1.00 63.11 C ATOM 2080 CA GLY B 230 174.880 57.021 10.570 1.00134.41 C 7452 7423 9102 23 329 500 C ANISOU 2080 CA GLY B 230 15788 16632 18648 -100 -3354 1020 C NZ I 3 172.989 68.165 -1.136 1.00 68.23 N ATOM 2081 C GLY B 230 175.730 56.029 11.344 1.00133.18 C

NZ 8238 8127 9560 73 381 400 N ANISOU 2081 C GLY B 230 15627 16369 18606 -78 -3571 1149 C I 3 173.898 72.265 4.073 1.00 40.20 C ATOM 2082 O GLY B 230 176.748 55.538 10.853 1.00134.02 O 4532 4594 6147 -548 -727 478 C ANISOU 2082 O GLY B 230 15470 16329 19124 -18 -3550 1214 O I 3 174.599 73.096 4.536 1.00 50.06 O ATOM 2083 N ASP B 231 175.293 55.722 12.560 1.00130.93 N 5757 5778 7486 -691 -883 550 O ANISOU 2083 N ASP B 231 15646 16147 17956 -129 -3763 1187 N N 173.183 71.463 4.812 1.00 51.00 N ATOM 2084 CA ASP B 231 176.062 54.885 13.470 1.00131.82 C

N 4907 5974 8497 -493 -1634 -269 N ANISOU 2084 CA ASP B 231 15796 16161 18128 -124 -4012 1308 C

173.382 71.348 6.244 1.00 53.84 C ATOM 2085 CB ASP B 231 176.667 55.764 14.550 1.00135.01 C 5354 6368 8734 -568 -1987 -311 C ANISOU 2085 CB ASP B 231 16304 16547 18446 -217 -4294 1252 C 172.225 70.559 6.856 1.00 54.51 C ATOM 2086 CG ASP B 231 175.693 56.818 15.026 1.00134.22 C 5702 6611 8398 -539 -2008 -305 C ANISOU 2086 CG ASP B 231 16481 16593 17924 -304 -4262 1115 C 171.188 71.199 7.768 1.00 49.85 C ATOM 2087 OD1 ASP B 231 174.836 56.496 15.878 1.00134.90 O 5394 6107 7439 -590 -2050 -426 C ANISOU 2087 OD1 ASP B 231 16901 16767 17588 -342 -4290 1132 O 170.575 70.104 8.617 1.00 46.67 C ATOM 2088 OD2 ASP B 231 175.762 57.957 14.517 1.00132.74 O 5190 5820 6723 -580 -2161 -382 C ANISOU 2088 OD2 ASP B 231 16178 16423 17834 -335 -4181 990 O 171.837 72.236 8.638 1.00 51.88 C ATOM 2089 C ASP B 231 175.148 53.861 14.124 1.00128.60 C 5664 6283 7765 -701 -2292 -535 C ANISOU 2089 C ASP B 231 15684 15822 17357 -119 -4021 1401 C 174.654 70.538 6.402 1.00 55.85 C ATOM 2090 O ASP B 231 175.219 53.634 15.337 1.00129.44 O 5374 6536 9312 -570 -2190 -211 C ANISOU 2090 O ASP B 231 16024 15929 17230 -169 -4243 1449 O 174.841 69.545 5.703 1.00 58.87 O ATOM 2091 N ARG B 232 174.285 53.255 13.312 1.00122.29 N 5645 6911 9813 -489 -2055 -102 O ANISOU 2091 N ARG B 232 14880 15072 16512 -61 -3771 1428 N N 175.533 70.947 7.313 1.00 59.12 N ATOM 2092 CA ARG B 232 173.296 52.294 13.791 1.00114.35 C

N 5708 6874 9882 -663 -2521 -249 N ANISOU 2092 CA ARG B 232 14148 14126 15172 -59 -3726 1515 C

176.680 70.093 7.620 1.00 64.45 C ATOM 2093 CB ARG B 232 171.931 52.970 13.944 1.00107.41 C 6161 7467 10861 -661 -2772 -144 C ANISOU 2093 CB ARG B 232 13538 13410 13861 -128 -3583 1411 C 177.338 70.819 8.777 1.00 65.22 C ATOM 2094 CG ARG I 3 232 171.068 52.349 15.015 1.00107.31 C 6322 7508 10951 -761 -3089 -215 C ANISOU 2094 CG ARG B 232 13896 13455 13421 -176 -3603 1473 C I 3 177.080 72.266 8.450 1.00 65.45 C ATOM 2095 CD ARG I 3 232 169.673 52.085 14.493 1.00104.52 C B 6350 7493 11027 -832 -2971 -355 C ANISOU 2095 CD ARG B 232 13677 13200 12837 -178 -3330 1461 C I 3 175.653 72.272 7.941 1.00 64.64 C ATOM 2096 NE ARG I 3 232 168.687 52.949 15.135 1.00104.18 N B 6470 7523 10570 -772 -2667 -388 C ANISOU 2096 NE ARG B 232 13925 13279 12379 -274 -3250 1341 N 3 176.213 68.701 8.025 1.00 73.83 C ATOM 2097 CZ ARG I i 232 167.921 52.595 16.166 1.00102.14 C 7487 8763 11803 -597 -2850 -44 C ANISOU 2097 CZ ARG B 232 14005 13061 11743 -332 -3212 1367 C 175.205 68.550 8.719 1.00 71.31 O ATOM 2098 NHl ARG B 232 167.056 53.468 16.672 1.00 99.70 N 7470 8576 11050 -610 -2896 -83 O ANISOU 2098 NHl ARG B 232 13933 12847 11101 -414 -3094 1238 N 176.946 67.691 7.573 1.00 86.84 N ATOM 2099 NH2 ARG B 232 168.011 51.373 16.686 1.00102.28 N ί 227 8920 10340 13737 -525 -2829 85 N ANISOU 2099 NH2 ARG B 232 14123 13013 11728 -306 -3270 1520 N i 176.398 66.344 7.502 1.00 98.10 C ATOM 2100 C ARG B 232 173.207 51.114 12.821 1.00106.74 C 10439 11850 14984 -442 -2772 187 C ANISOU 2100 C ARG B 232 13016 13091 14449 45 -3543 1618 C i 177.110 65.522 6.428 1.00100.05 C ATOM 2101 O ARG I 3 232 173.828 51.146 11.751 1.00105.67 O 10408 11987 15619 -348 -2564 296 C ANISOU 2101 O ARG B 232 12570 12872 14708 112 -3422 1602 O i 176.401 65.576 5.098 1.00 99.95 C ATOM 2102 N ALA I 3 233 172.446 50.082 13.198 1.00 99.06 N 10442 12005 15530 -281 -2111 276 C ANISOU 2102 N ALA I B 233 12257 12137 13244 55 -3503 1720 N i 177.341 65.775 3.929 1.00100.74 C ATOM 2103 CA ALA ] B 233 172.237 48.917 12.340 1.00 94.25 C 10252 11941 16082 -246 -1858 304 C ANISOU 2103 CA ALA B 233 11529 11452 12828 147 -3322 1817 C I 178.484 65.299 3.944 1.00 97.83 O ATOM 2104 CB ALA I i 233 171.274 47.942 12.989 1.00 92.74 C 9632 11434 16104 -227 -1945 379 O ANISOU 2104 CB ALA B 233 11640 11292 12305 126 -3292 1921 C I 176.865 66.499 2.903 1.00101.26 N ATOM 2105 C ALA B 233 171.705 49.338 10.966 1.00 90.32 C 10379 12009 16087 -235 -1520 247 N ANISOU 2105 C ALA B 233 10887 11002 12429 175 -2973 1690 C I 176.332 65.560 8.798 1.00106.25 C ATOM 2106 O ALA B 233 170.774 50.143 10.875 1.00 87.78 O 11666 12941 15761 -461 -3093 242 C ANISOU 2106 O ALA B 233 10712 10818 11822 110 -2803 1552 O I 176.810 65.989 9.863 1.00102.24 O ATOM 2107 N GLY B 234 172.300 48.788 9.909 1.00 89.52 N ί 227 11261 12407 15178 -532 -3353 208 O ANISOU 2107 N GLY B 234 10517 10777 12718 267 -2810 1708 N I 175.705 64.398 8.662 1.00115.69 N ATOM 2108 CA GLY B 234 171.874 49.057 8.546 1.00 89.09 C ί 228 12948 14213 16798 -391 -3022 330 N ANISOU 2108 CA GLY B 234 10360 10747 12742 290 -2426 1568 C i 175.504 63.462 9.747 1.00127.55 C ATOM 2109 C GLY B 234 172.413 50.339 7.917 1.00 95.51 C 14661 15770 18032 -393 -3250 407 C ANISOU 2109 C GLY B 234 10986 11573 13730 279 -2367 1442 C i 174.077 63.571 10.282 1.00127.77 C ATOM 2110 O GLY B 234 172.206 50.568 6.718 1.00 92.33 O 15042 15959 17546 -428 -3203 340 C ANISOU 2110 O GLY B 234 10494 11167 13418 305 -2057 1340 O i 173.657 62.396 11.146 1.00128.19 C ATOM 2111 N ILE B 235 173.098 51.181 8.700 1.00101.20 N 15312 16074 17319 -416 -3359 444 C ANISOU 2111 N ILE B 235 11661 12298 14490 235 -2664 1448 N i 172.176 62.401 11.481 1.00125.37 C ATOM 2112 CA ILE B 235 173.570 52.475 8.183 1.00100.91 C 15292 15860 16482 -434 -3172 379 C ANISOU 2112 CA ILE B 235 11460 12270 14611 210 -2612 1325 C I 171.473 63.405 11.292 1.00124.27 O ATOM 2113 CB ILE B 235 172.553 53.629 8.456 1.00 72.53 C 15248 15777 16193 -467 -2990 245 C ANISOU 2113 CB ILE B 235 8092 8849 10617 117 -2552 1183 C I 171.690 61.271 11.978 1.00124.63 N ATOM 2114 CGI ILE B 235 172.219 53.738 9.952 1.00 72.39 C 15371 15814 16168 -411 -3207 480 N ANISOU 2114 CGI ILE B 235 8338 8909 10257 39 -2859 1223 C 175.761 62.054 9.213 1.00133.27 C ATOM 2115 CD1 ILE B 235 172.033 55.190 10.429 1.00 67.61 C

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 c c c c c c o o c c c c c c c c o o o o c c o o c c c c o o c c o o c c c c c c c c o o c c o o c c c c c c o o c c o c c c c c c o o c c o o

 B

O ATOM 2881 C ARG B 331 151.607 77.041 5.916 1.00 56.57 C O ANISOU 2881 C ARG B 331 7732 6246 7517 523 41 -827 C

ATOM 2882 O ARG B 331 151.097 77.338 6.999 1.00 58.75 o ANISOU 2882 O ARG B 331 8124 6474 7723 621 222 -951 o O ATOM 2883 N HIS B 332 152.408 75.996 5.800 1.00 51.38 N O ANISOU 2883 N HIS B 332 7024 5743 6754 364 -60 -763 N

ATOM 2884 CA HIS B 332 152.699 75.178 6.963 1.00 44.61 C

S ANISOU 2884 CA HIS B 332 6235 5010 5706 300 6 -812 c 3 ATOM 2885 CB HIS B 332 153.231 73.819 6.548 1.00 37.46 c

ANISOU 2885 CB HIS B 332 5179 4271 4783 180 -72 -684 c i ATOM 2886 CG HIS B 332 152.181 72.856 6.152 1.00 45.89 c

ANISOU 2886 CG HIS B 332 6027 5446 5962 244 24 -601 c 3 ATOM 2887 ND1 HIS B 332 151.504 72.920 4.938 1.00 47.90 N

ANISOU 2887 NDl HIS B 332 6120 5683 6394 292 -31 -531 N 3 ATOM 2888 CE1 HIS B 332 150.650 71.927 4.855 1.00 43.87 c

ANISOU 2888 CE1 HIS B 332 5424 5276 5968 306 36 -473 c O ATOM 2889 NE2 HIS B 332 150.724 71.216 5.969 1.0047.12 N O ANISOU 2889 NE2 HIS B 332 5868 5763 6271 284 169 -488 N 3 ATOM 2890 CD2 HB B 332 151.665 71.777 6.793 1.0049.15 C

ANISOU 2890 CD2 HIS B 332 6351 5980 6343 251 154 -565 c i ATOM 2891 C HIS B 332 153.724 75.838 7.858 1.00 53.06 c

ANISOU 2891 C HIS B 332 7570 5994 6597 195 -76 -936 c i O ATOM 2892 O HIS B 332 153.569 75.863 9.079 1.00 57.74 o

O ANISOU 2892 O HIS B 332 8339 6600 6998 217 24 -1049 o i ATOM 2893 N LEU B 333 154.775 76.365 7.231 1.00 50.28 N

ANISOU 2893 N LEU B 333 7251 5551 6301 69 -262 -907 N ATOM 2894 CA LEU E 333 155.878 76.985 7.927 1.00 56.12 c ANISOU 2894 CA LEU ] ! 333 8198 6200 6925 -81 -408 -1002 c i ATOM 2895 CB LEU B 333 156.791 77.614 6.901 1.00 62.16 c

ANISOU 2895 CB LEU ] ! 333 8914 6841 7862 -192 -563 -921 c 3 ATOM 2896 CG LEU E 333 158.168 77.023 6.708 1.00 63.00 c

ANISOU 2896 CG LEU ] ! 333 8918 7033 7985 -385 -733 -799 c 3 ATOM 2897 CD2 LEU I 333 159.156 77.699 7.618 1.00 54.08 c

ANISOU 2897 CD2 LEU 3 333 7963 5806 6779 -558 -916 -901 c O ATOM 2898 CD1 LEU I 333 158.526 77.267 5.279 1.00 66.92 c O ANISOU 2898 CD1 LEU 3 333 9282 7461 8684 -404 -746 -655 c O ATOM 2899 C LEU I 333 155.396 78.092 8.848 1.00 66.65 c O ANISOU 2899 C LEU 1 333 9808 7356 8159 -5 -316 -1215 c

ATOM 2900 O LEU ] 333 156.017 78.405 9.863 1.00 72.53 o ANISOU 2900 O LEU ! 333 10792 8060 8707 -118 -408 -1349 o i O ATOM 2901 N ARG 334 154.282 78.703 8.481 1.00 64.64 N

O ANISOU 2901 N ARG B 3 334 9530 6983 8047 190 -141 -1246 N i ATOM 2902 CA ARG B 3 334 153.808 79.844 9.211 1.00 68.23 c

ANISOU 2902 CA ARG 1 B 334 10249 7217 8460 294 -9 -1448 c ATOM 2903 CB ARG B 3 334 152.976 80.731 8.301 1.00 62.76 c ANISOU 2903 CB ARG I B 334 9462 6334 8051 478 91 -1402 c i ATOM 2904 CG ARG B 3 334 153.828 81.762 7.609 1.00 62.47 c

ANISOU 2904 CG ARG 1 B 334 9512 6074 8151 364 -89 -1390 c ATOM 2905 CD ARG B 3 334 153.159 82.263 6.362 1.00 62.02 c i ANISOU 2905 CD ARG 1 B 334 9278 5913 8375 519 -59 -1227 c

ATOM 2906 NE ARG B 3 334 153.974 83.269 5.691 1.00 67.63 N ANISOU 2906 NE ARG I B 334 10085 6394 9220 412 -202 -1187 N ATOM 2907 CZ ARG B i 334 153.754 83.710 4.453 1.00 72.71 c

B 329 ANISOU 2907 CZ ARG I B 334 10604 6951 10073 486 -241 -996 c 3 329 O ATOM 2908 NHl ARG I B 334 152.742 83.209 3.749 1.00 75.45 N B 329 O ANISOU 2908 NHl ARG 334 10721 7439 10508 658 -192 -840 N 3 330 ATOM 2909 NH2 ARG I 334 154.552 84.641 3.919 1.00 71.15 N B 330 ANISOU 2909 NH2 ARG 334 10514 6527 9995 375 -344 -947 N B 330 ATOM 2910 C ARG I 334 153.074 79.446 10.490 1.00 82.51 C B 330 ANISOU 2910 C ARG ! 334 12204 9109 10039 401 222 -1574 c 3 330 ATOM 2911 O ARG I 334 151.916 79.817 10.702 1.00 84.62 o

ANISOU 2911 O ARG ! 334 12479 9289 10384 622 494 -1632 o ATOM 2912 N GLN I 335 153.767 78.664 11.324 1.00 88.39 N ANISOU 2912 N GLN 1 335 13052 10024 10510 250 122 -1587 N ATOM 2913 CA GLN B 335 153.413 78.453 12.730 1.00 90.10 C ANISOU 2913 CA GLN B 335 13537 10296 10402 294 296 -1729 c ATOM 2914 CB GLN B 335 152.178 77.573 12.878 1.00 86.04 c ANISOU 2914 CB GLN B 335 12828 9936 9926 486 608 -1625 c ATOM 2915 CG GLN B 335 151.932 76.676 11.682 1.00 84.23 c ANISOU 2915 CG GLN B 335 12170 9850 9985 493 549 -1384 c

O O ATOM 2916 CD GLN B 335 150.587 76.950 11.040 1.00 86.54 c

O O ANISOU 2916 CD GLN B 335 12230 10073 10579 716 772 -1332 c

ATOM 2917 OE1 GLN B 335 149.777 76.036 10.860 1.00 86.21 o ANISOU 2917 OE1 GLN B 335 11924 10175 10655 788 906 -1195 o ATOM 2918 NE2 GLN B 335 150.328 78.215 10.718 1.00 86.38 N ANISOU 2918 NE2 GLN B 335 12295 9818 10708 824 807 -1428 N ATOM 2919 C GLN B 335 154.593 77.838 13.465 1.00 90.04 c ANISOU 2919 C GLN B 335 13668 10439 10104 63 37 -1715 c ATOM 2920 O GLN B 335 155.623 78.484 13.627 1.00 90.66 o ANISOU 2920 O GLN B 335 13924 10409 10114 -122 -230 -1808 TER 2922 GLN B 335

HET ATM 2921 OAD DRG C 162.991 49.038 5.565 1.00 28.90 o HETATM 2922 CAQ DRG C 163.951 49.693 5.137 1.00 31.88 c HETATM 2923 CAS DRG C 165.012 50.082 5.948 1.00 28.82 c HETATM 2924 CAJ DRG C 165.024 49.798 7.306 1.00 26.98 c HETATM 2925 CAH DRG C 166.130 50.171 8.071 1.00 28.53 c HETATM 2926 CAN DRG C 167.237 50.842 7.499 1.00 31.26 c HETATM 2927 CAA DRG C 168.386 51.246 8.285 1.00 24.52 c HETATM 2928 CAO DRG C 167.200 51.163 6.135 1.00 30.95 c ΗΕΤΑΤΜ 2929 CAB DRG C 168.248 51.869 5.487 1.00 23.50 C HETATM 2982 O HOH S 20 171.080 57.987 13.953 1.00 45.06 O HETATM 2930 CAT DRG C 166.056 50.821 5.426 1.00 31.37 C HETATM 2983 O HOH S 21 148.067 47.124 -0.587 1.00 45.29 o HET ATM 2931 OAL DRG C 166.098 51.093 4.116 1.00 29.82 o HETATM 2984 O HOH S 22 143.902 55.932 -14.363 1.00 63.60 o HETATM 2932 CAU DRG C 165.125 50.661 3.280 1.00 23.20 c HETATM 2986 O HOH S 24 150.530 40.637 7.539 1.00 55.40 o HETATM 2933 CAR DRG C 164.030 49.989 3.787 1.00 24.45 c HETATM 2987 O HOH S 25 166.897 51.082 11.483 1.00 49.70 o HETATM 2934 CAI DRG C 163.050 49.542 2.893 1.00 23.70 c HETATM 2988 O HOH S 26 182.591 60.441 -1.208 1.00 53.67 o HETATM 2935 CAF DRG C 163.148 49.831 1.533 1.00 24.90 c HETATM 2989 O HOH S 27 172.503 46.354 5.924 1.00 51.32 o HETATM 2936 CAG DRG C 164.257 50.533 1.042 1.00 24.70 c HETATM 2991 O HOH S 29 197.473 47.430 -5.671 1.00 56.88 o HETATM 2937 CAP DRG C 165.250 50.993 1.925 1.00 29.90 c HETATM 2992 O HOH S 30 154.281 64.868 15.755 1.00 61.97 o HETATM 2938 CAK DRG C 166.386 51.724 1.462 1.00 26.20 c HETATM 2993 O HOH S 31 194.426 33.302 6.916 1.00 47.03 o HETATM 2939 CAM DRG C 167.789 51.131 1.752 1.00 39.78 c HETATM 2994 O HOH S 32 163.586 73.804 8.275 1.00 40.52 o HETATM 2940 OAE DRG C 167.893 49.935 2.148 1.00 40.47 o HETATM 2995 O HOH S 33 181.340 40.097 -2.774 1.00 48.13 o HETATM 2941 OAC DRG C 168.731 51.931 1.552 1.0041.66 o HETATM 2996 O HOH S 34 184.998 42.705 12.196 1.00 50.78 o HETATM 2942 OAD DRG C 160.821 53.562 -0.957 1.00 29.91 o HETATM 2997 O HOH S 35 151.669 47.690 -11.983 1.00 33.83 o HETATM 2943 CAQ DRG C 161.917 53.977 -0.557 1.00 27.38 c HETATM 2998 O HOH S 36 171.381 82.460 13.092 1.00 72.55 o HETATM 2944 CAS DRG C 162.812 54.579 -1.407 1.00 20.36 c HETATM 2999 O HOH S 37 164.720 55.181 -7.543 1.00 35.15 o HETATM 2945 CAJ DRG C 162.507 54.745 2.761 1.00 19.81 c HETATM 3000 O HOH S 38 152.216 75.299 -11.371 1.00 64.67 o HETATM 2946 163.441 55.403 -3.591 1.00 24.49 c HETATM 3001 O HOH S 39 162.728 61.240 2.446 1.00 52.37 o HETATM 2947 CAN DRG C 164.687 55.855 -3.089 1.00 28.71 c HETATM 3002 O HOH S 40 157.809 85.373 -5.397 1.00 49.67 o HETATM 2948 CAA DRG C 165.671 56.485 -3.925 1.00 28.17 c HETATM 3003 O HOH S 41 160.833 54.824 -11.983 1.00 53.47 o HETATM 2949 CAO DRG C 164.978 55.677 -1.721 1.00 26.46 c HETATM 3004 O HOH S 42 172.438 36.666 11.131 1.00 50.31 o HETATM 2950 CAB DRG C 166.188 56.089 -1.114 1.00 18.84 c HETATM 3005 O HOH S 43 143.215 55.825 1.242 1.00 51.98 o HETATM 2951 CAT DRG C 164.038 55.032 -0.924 1.00 24.41 c HETATM 3006 O HOH S 44 178.194 34.813 -9.692 1.00 61.99 o HETATM 2952 OAL DRG C 164.378 54.935 0.369 1.00 27.02 o HETATM 3007 O HOH S 45 160.209 55.971 -9.794 1.00 51.89 o HETATM 2953 CAU DRG C 163.488 54.378 1.221 1.00 27.07 c HETATM 3009 O HOH S 47 170.559 46.042 2.157 1.00 40.56 o HETATM 2954 CAR DRG C 162.274 53.883 0.769 1.00 24.72 c HETATM 3011 O HOH S 49 176.760 53.698 2.889 1.00 56.49 o HETATM 2955 CAI DRG C 161.376 53.311 1.662 1.00 23.42 c HETATM 3012 O HOH S 50 168.790 62.275 2.328 1.00 60.56 o HETATM 2956 CAF DRG C 161.750 53.230 2.996 1.00 24.17 c HETATM 3013 O HOH S 51 167.855 55.504 4.837 1.00 40.62 o HETATM 2957 CAG DRG C 162.974 53.719 3.444 1.00 24.73 c HETATM 3014 O HOH S 52 177.579 50.250 -7.113 1.00 55.88 o HETATM 2958 CAP DRG C 163.876 54.296 2.556 1.00 29.50 c HETATM 3015 O HOH S 53 155.929 68.342 -6.155 1.00 42.77 o HETATM 2959 CAK DRG C 165.123 54.798 3.007 1.00 31.35 c HETATM 3016 O HOH S 54 187.365 29.710 12.394 1.00 49.65 o HETATM 2960 CAM DRG C 165.455 56.308 2.721 1.00 33.32 c HETATM 3017 O HOH S 55 185.843 27.691 12.218 1.00 51.08 o HETATM 2961 OAE DRG C 164.570 57.125 2.437 1.00 34.51 o HETATM 3018 O HOH S 56 190.462 26.460 7.158 1.00 50.01 o HETATM 2962 OAC DRG C 166.634 56.666 2.839 1.0040.95 o HETATM 3019 O HOH S 57 163.171 48.532 17.270 1.00 48.75 o HETATM 2963 0 HOH S 1 168.713 53.789 -0.291 1.00 35.33 o HETATM 3020 O HOH S 58 164.548 48.001 15.528 1.00 60.23 o HETATM 2964 0 HOH S 2 161.892 53.727 16.866 1.00 49.67 o HETATM 3021 O HOH S 59 143.593 59.258 12.238 1.00 63.87 o HETATM 2965 0 HOH S 3 164.969 59.956 2.543 1.00 37.40 o HETATM 3022 O HOH S 60 144.484 59.906 14.347 1.00 71.48 o HETATM 2966 0 HOH S 4 153.816 51.547 -17.356 1.00 35.89 o HETATM 3023 O HOH S 61 152.669 45.115 16.448 1.00 43.47 o HETATM 2967 0 HOH S 5 173.955 67.623 4.394 1.00 44.22 o HETATM 3024 O HOH S 62 160.263 38.016 17.761 1.00 48.84 o HETATM 2968 0 HOH S 6 160.329 36.676 11.944 1.00 55.15 o HETATM 3025 O HOH S 63 152.484 64.476 18.117 1.00 65.15 o HETATM 2969 0 HOH S 7 167.121 68.307 2.491 1.00 43.22 o HETATM 3026 O HOH S 64 149.649 67.575 5.246 1.00 53.28 o HETATM 2970 0 HOH S 8 174.241 45.104 7.023 1.00 39.35 o HETATM 3028 O HOH S 66 154.393 85.153 -5.360 1.00 42.89 o HETATM 2971 0 HOH S 9 147.991 51.757 8.039 1.00 42.30 o HETATM 3029 O HOH S 67 163.677 82.527 -9.406 1.00 55.89 o HETATM 2972 0 HOH S 10 150.720 42.063 5.341 1.00 55.82 o HETATM 3030 O HOH S 68 163.984 77.274 -8.161 1.00 46.95 o HETATM 2973 0 HOH S 11 155.127 75.108 -8.066 1.00 54.25 o HETATM 3031 O HOH S 69 176.278 65.478 13.005 1.00 69.67 o HETATM 2974 0 HOH S 12 154.172 39.544 -3.767 1.00 53.24 o HETATM 3033 0 HOH S 71 149.765 70.612 2.125 1.00 53.58 o HETATM 2975 0 HOH S 13 165.300 57.764 -7.952 1.00 41.58 o HETATM 3039 S S04 E 1 190.873 52.635 : !.687 1.00209.77 s HETATM 2976 0 HOH S 14 162.850 89.254 -6.796 1.00 52.78 o HETATM 3040 01 S04 E 1 191.344 51.848 1.550 1.00208.46 o HETATM 2977 0 HOH S 15 154.964 70.741 -7.727 1.00 45.98 o HETATM 3041 02 S04 E 1 189.413 52.472 2.690 1.00210.80 o HETATM 2978 0 HOH S 16 164.131 62.771 -1.020 1.00 51.78 o HETATM 3042 03 S04 E 1 191.451 52.156 3.943 1.00210.05 o HETATM 2979 0 HOH S 17 152.520 70.191 15.623 1.00 58.84 o HETATM 3043 04 S04 E 1 191.281 54.037 2.527 1.00209.37 o HETATM 2980 0 HOH S 18 166.251 62.142 0.998 1.00 47.15 o END

Table 9. DMXAA-hSTING^{sl62A/G230I/Q2661} REMARK 3 ORIGIN FOR THE GROUP (A): 119.7412 -45.6180 0.9079

REMARK 3 T TENSOR

complex REMARK 3 Ti l 0.4193 T22 0.4961

REMARK 3 T33 0.3419 T12 0.1443

REMARK 3 T13 0.0895 T23 0.1533

REMARK 3

REMARK 3 REMARK 3 Ll l 4.6250 L22 6.8599

REMARK 3 REFINEMENT. REMARK 3 L33 2.9736 L12 -3.3531

REMARK 3 PROGRAM : PHENIX (phenix.refme: 1.8.2 1309) REMARK 3 L13 0.4680 L23 -0.1759

REMARK 3 AUTHORS : Adams,Afonine,Burnley,Chen,Davis,Echols,Gildea, REMARK 3 S TENSOR

REMARK 3 : Gopal,Gros,Grosse-Kunstleve,Headd,Hung,Immormino, REMARK 3 Sl l ■0.8048 S12: -0.9653 S13: -0.5231

REMARK 3 : Ioerger,McCoy,McKee,Moriarty,Pai,Read,Richardson, REMARK 3 S21 1.3663 S22: 0.5796 S23: 0.1655

REMARK 3 : Richardson,Romo,Sacchettini,Sauter,Smith,Storoni, REMARK 3 S31 0.2873 S32: 0.2438 S33: 0.2232

REMARK 3 : Terwilliger,Zwart REMARK 3 TLS GROUP : 2

REMARK 3 REMARK 3 SELECTION: chain Ά' and (resid 186 through 211 )

REMARK 3 REFINEMENT TARGET : ML REMARK 3 ORIGIN FOR THE GROUP (A): 129.3530 -48.7083 -7.1009

REMARK 3 REMARK 3 T TENSOR

REMARK 3 DATA USED IN REFINEMENT. REMARK 3 Ti l 0.4212 T22 0.6459

REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.370 REMARK 3 T33 0.6367 T12 0.1380

REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 128.671 REMARK 3 T13 0.0329 T23 -0.0528

REMARK 3 MIN(FOBS/SIGMA FOBS) : 1.35 REMARK 3

REMARK 3 COMPLETENESS FOR RANGE (%) : 99. 1 REMARK 3 Ll l 3.5990 L22 9.5628

REMARK 3 NUMBER OF REFLECTIONS : 19048 REMARK 3 L33 2.8698 L12 -3.6331

REMARK 3 NUMBER OF REFLECTIONS (NON-ANOMALOUS) : 19048 REMARK 3 L13 1.0100 L23 -0.5546

REMARK 3 REMARK 3 S TENSOR

REMARK 3 FLT TO DATA USED IN REFINEMENT. REMARK 3 Sl l -0.0638 S12: 0.2429 S13: -0.8055

REMARK 3 R VALUE (WORKTNG + TEST SET) : 0.1893 REMARK 3 S21 0.1232 S22: 0.2133 S23: -0.3000

REMARK 3 R VALUE (WORKING SET) : 0.1870 REMARK 3 S31 0.5832 S32: 0.3737 S33: -0.0249

REMARK 3 FREE R VALUE : 0.2310 REMARK 3 TLS GROUP : 3

REMARK 3 FREE R VALUE TEST SET SIZE ( ) : 5.15 REMARK 3 SELECTION: chain Ά' and (resid 212 through 227 )

REMARK 3 FREE R VALUE TEST SET COUNT : 981 REMARK 3 ORIGIN FOR THE GROUP (A): 129.1486 -52.5547 -12.8258

REMARK 3 REMARK 3 T TENSOR

REMARK 3 FLT TO DATA USED IN REFINEMENT (IN BINS). REMARK 3 Ti l 0.4393 T22: 0.5281

REMARK 3 BIN RESOLUTION RANGE COMPL. NWORK NFREE RWORK REMARK 3 T33 0.5919 T12: 0.0322

RFREE REMARK 3 T13 -0.0127 T23: 0.1194

REMARK 3 1 128.8606 - 4.5338 1.00 2698 133 0.1721 0.2114 REMARK 3

REMARK 3 2 4.5338 - 3.5985 1.00 2593 146 0.15540.1881 REMARK 3 Ll l 5.8586 L22: 9.3215

REMARK 3 3 3.5985 - 3.1436 1.00 2587 136 0.1775 0.2098 REMARK 3 L33 8.1146 L12: 6.4837

REMARK 3 4 3.1436 - 2.8562 1.00 2551 135 0.2056 0.2800 REMARK 3 L13 -6.5623 L23: -5.5758

REMARK 3 5 2.8562 - 2.6514 1.00 2559 140 0.2293 0.2668 REMARK 3 S TENSOR

REMARK 3 6 2.6514 - 2.4951 1.00 2546 142 0.2922 0.3880 REMARK 3 Sl l : -0.8869 S12: 1.2379 S13 -0.7595

REMARK 3 7 2.4951 - 2.3701 1.00 2533 149 0.2916 0.3274 REMARK 3 S21 : -0.4167 S22: 1.1681 S23 0.6136

REMARK 3 REMARK 3 S31 : 0.0975 S32: -1.4546 S33 -0.1067

REMARK 3 BULK SOLVENT MODELLING. REMARK 3 TLS GROUP : 4

REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL REMARK 3 SELECTION: chain Ά' and (resid 228 through 242 )

REMARK 3 SOLVENT RADIUS : 1.11 REMARK 3 ORIGIN FOR THE GROUP (A): 110.4692 -51.7135 -1.3574

REMARK 3 SHRINKAGE RADIUS : 0.90 REMARK 3 T TENSOR

REMARK 3 GRID STEP FACTOR : 4.00 REMARK 3 Ti l 0.7933 T22 0.5352

REMARK 3 REMARK 3 T33 0.8596 T12 -0.0041

REMARK 3 ERROR ESTIMATES. REMARK 3 T13 0.2322 T23 0.1112

REMARK 3 COORDINATE ERROR (MAXIMUM -LIKELIHOOD BASED) : 0.30 REMARK 3

REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : REMARK 3 Ll l 7.5537 L22: 2.8609

22.08 REMARK 3 L33 1.4922 L12: -4.5153

REMARK 3 REMARK 3 L13 -2.2277 L23: 1.0483

REMARK 3 STRUCTURE FACTORS CALCULATION ALGORITHM : FFT REMARK 3 S TENSOR

REMARK 3 REMARK 3 Sl l : -0.9886 S12: -1.1618 S13: -1.8144

REMARK 3 DEVIATIONS FROM IDEAL VALUES. REMARK 3 S21 : 0.0203 S22: 0.2433 S23: 0.9635

REMARK 3 RMSD MAX COUNT REMARK 3 S31 : -0.0130 S32: -0.0466 S33: 0.4012

REMARK 3 BOND : 0.007 0.040 3034 REMARK 3 TLS GROUP : 5

REMARK 3 ANGLE : 1.203 8.976 4122 REMARK 3 SELECTION: chain Ά' and (resid 243 through 280 )

REMARK 3 CHIRALITY : 0.075 0.371 448 REMARK 3 ORIGIN FOR THE GROUP (A): 124.7540 -41.4323 -13.6540

REMARK 3 PLANARLTY : 0.004 0.039 542 REMARK 3 T TENSOR

REMARK 3 DIHEDRAL : 18.321 82.369 1138 REMARK 3 Ti l 0.3074 T22 0.3011

REMARK 3 MIN NONBONDED DISTANCE : 1.922 REMARK 3 T33 0.2748 T12 -0.0078

REMARK 3 REMARK 3 T13 0.0100 T23 0.0303

REMARK 3 MOLPROBLTY STATISTICS. REMARK 3

REMARK 3 ALL-ATOM CLASHSCORE : 7.67 REMARK 3 Ll l 3.6448 L22 2.3155

REMARK 3 RAMACHANDRAN PLOT: REMARK 3 L33 1.7574 L12 -1.9552

REMARK 3 OUTLIERS : 0.56 % REMARK 3 L13 -0.0407 L23 -0.1114

REMARK 3 ALLOWED : 3.89 % REMARK 3 S TENSOR

REMARK 3 FAVORED : 95.56 % REMARK 3 Sl l -0.1020 S12: -0.0173 S13: -0.1125

REMARK 3 ROTAMER OUTLIERS : 11.71 % REMARK 3 S21 0.1136 S22: 0.0133 S23: -0.1586

REMARK 3 CBETA DEVIATIONS : 0 REMARK 3 S31 0.0827 S32: 0.2233 S33: 0.0722

REMARK 3 REMARK 3 TLS GROUP : 6

REMARK 3 ATOMIC DISPLACEMENT PARAMETERS. REMARK 3 SELECTION: chain Ά' and (resid 281 through 314 )

REMARK 3 WILSON B : 52.20 REMARK 3 ORIGIN FOR THE GROUP (A): 123.3640 -32.6276 -3.4192

REMARK 3 RMS(B ISO OR EQUIVALENT BONDED) : 8.54 REMARK 3 T TENSOR

REMARK 3 ATOMS NUMBER OF ATOMS REMARK 3 Ti l 0.4307 T22: 0.4987

REMARK 3 ISO. ANISO. REMARK 3 T33 0.3607 T12: 0.0528

REMARK 3 ALL : 3033 2928 REMARK 3 T13 -0.0232 T23: -0.0691

REMARK 3 ALL (NO H) : 3033 2928 REMARK 3

REMARK 3 SOLVENT : 58 0 REMARK 3 Ll l 5.0093 L22 6.6833

REMARK 3 NON-SOLVENT : 2975 2928 REMARK 3 L33 6.8768 L12 -2.5420

REMARK 3 HYDROGENS : 0 0 REMARK 3 L13 -0.4223 L23 -1.0414

REMARK 3 REMARK 3 S TENSOR

REMARK 3 TLS DETAILS. REMARK 3 Sl l ■0.3563 S12: -0.7204 S13: -0.0370

REMARK 3 NUMBER OF TLS GROUPS: 19 REMARK 3 S21 1.1416 S22: 0.4752 S23: ■0.2161

REMARK 3 ORIGIN: CENTER OF MASS REMARK 3 S31 -0.6150 S32: 0.5594 S33: -0.1028

REMARK 3 TLS GROUP : 1 REMARK 3 TLS GROUP : 7

REMARK 3 SELECTION: chain 'A' and (resid 154 through 185 ) REMARK 3 SELECTION: chain 'Α' and (resid 315 through 324 ) REMARK 3 ORIGIN FOR THE GROUP (A): 136.1529 -33.2184 - 19.3637 REMARK 3 ORIGIN FOR THE GROUP (A): 85.9333 -53.1198 - 4.2411

REMARK 3 T TENSOR REMARK 3 T TENSOR

REMARK 3 Ti l 1.2099 T22 1.0982 REMARK 3 Ti l 0.3714 T22 0.2747

REMARK 3 T33 1.0451 T12 -0.0360 REMARK 3 T33 0.5722 T12 -0.0192

REMARK 3 T13 0.0766 T23 0.2092 REMARK 3 T13 -0.0126 T23: -0.0928

REMARK 3 L TENSOR REMARK 3 L TENSOR

REMARK 3 Ll l 7.4924 L22 8.3097 REMARK 3 Ll l 3.3449 L22 2.0165

REMARK 3 L33 3.9134 L12 -7.5601 REMARK 3 L33 5.6917 L12 -1.8933

REMARK 3 L13 -2.5458 L23 3.9627 REMARK 3 L13 1.8124 L23 0.8956

REMARK 3 S TENSOR REMARK 3 S TENSOR

REMARK 3 Sl l 1.0706 S12 0.5115 S13 0.7413 REMARK 3 Sl l 0.4190 S12 1.2640 S13 -1.7916

REMARK 3 S21 -2.3931 S22 0.2034 S23 -0.4202 REMARK 3 S21 -0.2402 S22 -0.4122 S23 0.0219

REMARK 3 S31 -1.4970 S32 1.0416 S33 -1.1149 REMARK 3 S31 -0.1884 S32 -0.4293 S33 0.0260

REMARK 3 TLS GROUP : 8 REMARK 3 TLS GROUP : 14

REMARK 3 SELECTION: chain A' and (resid 325 through 335 ) REMARK 3 SELECTION: chain 'Β' and (resid 252 through 262 )

REMARK 3 ORIGIN FOR THE GROUP (A): 138.2183 -41.3718 6.6489 REMARK 3 ORIGIN FOR THE GROUP (A): 90.2196 -50.5140 - 6.8148

REMARK 3 T TENSOR REMARK 3 T TENSOR

REMARK 3 Ti l 0.4830 T22 0.6805 REMARK 3 Ti l 0.3741 T22 0.3438

REMARK 3 T33 0.7524 T12 0.0984 REMARK 3 T33 0.5056 T12 0.0020

REMARK 3 T13 0.0045 T23 -0.1937 REMARK 3 T13 0.0368 T23 -0.0219

REMARK 3 L TENSOR REMARK 3 L TENSOR

REMARK 3 Ll l 3.9316 L22 9.9442 REMARK 3 Ll l 6.9716 L22 3.5972

REMARK 3 L33 4.3889 L12 0.7967 REMARK 3 L33 0.3302 L12 4.8886

REMARK 3 L13 -3.5976 L23 2.5293 REMARK 3 L13 -0.2250 L23 -0.4021

REMARK 3 S TENSOR REMARK 3 S TENSOR

REMARK 3 Sl l -0.0798 S12 -1.5666 S13 2.2980 REMARK 3 Sl l -0.6307 S12 0.1548 S13 -0.3940

REMARK 3 S21 0.1616 S22 0.8716 S23 0.0533 REMARK 3 S21 -0.4735 S22 0.4279 S23 -0.0522

REMARK 3 S31 -0.9688 S32 1.3146 S33 -0.7372 REMARK 3 S31 0.1429 S32 -0.0110 S33 0.1038

REMARK 3 TLS GROUP : 9 REMARK 3 TLS GROUP : 15

REMARK 3 SELECTION: chain 'Β' and (resid 154 through 185 ) REMARK 3 SELECTION: chain 'Β' and (resid 263 through 280 )

REMARK 3 ORIGIN FOR THE GROUP (A): 102.7779 -46.2422 - 15.6896 REMARK 3 ORIGIN FOR THE GROUP (A): 107.3523 -32.3148 3.4381

REMARK 3 T TENSOR REMARK 3 T TENSOR

REMARK 3 Ti l 0.3790 T22 0.4564 REMARK 3 Ti l 0.3575 T22 0.4111

REMARK 3 T33 0.4948 T12 -0.0780 REMARK 3 T33 0.2047 T12 0.0400

REMARK 3 T13 0.1193 T23 -0.1808 REMARK 3 T13 -0.0095 T23: -0.0117

REMARK 3 L TENSOR REMARK 3 L TENSOR

REMARK 3 Ll l 5.0670 L22 9.2284 REMARK 3 Ll l 4.1938 L22 7.9005

REMARK 3 L33 1.9220 L12 6.1333 REMARK 3 L33 7.0490 L12 3.5052

REMARK 3 L13 -0.3197 L23 -1.2094 REMARK 3 L13 2.3469 L23 5.1477

REMARK 3 S TENSOR REMARK 3 S TENSOR

REMARK 3 Sl l -0.7388 S12 0.8656 S13 -0.5878 REMARK 3 Sl l -0.0007 S12 -0.7426 S13 0.1759

REMARK 3 S21 -0.7892 S22 0.2346 S23 0.4003 REMARK 3 S21 0.2832 S22 -0.1936 S23 -0.0761

REMARK 3 S31 0.4546 S32 -0.3021 S33 0.5353 REMARK 3 S31 -0.2331 S32 -0.0177 S33 0.2045

REMARK 3 TLS GROUP : 10 REMARK 3 TLS GROUP : 16

REMARK 3 SELECTION: chain 'Β' and (resid 186 through 197 ) REMARK 3 SELECTION: chain 'Β' and (resid 281 through 300 )

REMARK 3 ORIGIN FOR THE GROUP (A) 89.4343 -60.0520 -14.5866 REMARK 3 ORIGIN FOR THE GROUP (A): 99.3068 -29.4630 - 6.9766

REMARK 3 T TENSOR REMARK 3 T TENSOR

REMARK 3 Ti l 0.7926 T22 0.8090 REMARK 3 Ti l 0.3660 T22 0.3222

REMARK 3 T33 0.7893 T12 -0.2621 REMARK 3 T33 0.3279 T12 0.0265

REMARK 3 T13 0.0833 T23 -0.0286 REMARK 3 T13 0.0158 T23 0.0473

REMARK 3 L TENSOR REMARK 3 L TENSOR

REMARK 3 Ll l 4.1177 L22 2.1948 REMARK 3 Ll l 5.4311 L22 8.2757

REMARK 3 L33 4.0533 L12 3.0564 REMARK 3 L33 4.2934 L12 -1.9276

REMARK 3 L13 -1.0144 L23 -0.7338 REMARK 3 L13 -1.7369 L23 5.9517

REMARK 3 S TENSOR REMARK 3 S TENSOR

REMARK 3 Sl l -0.2529 S12 0.1725 S13 -0.4022 REMARK 3 Sl l -0.0824 S12 -0.1743 S13 0.1487

REMARK 3 S21 -0.9500 S22 0.4807 S23 -0.1411 REMARK 3 S21 -0.2388 S22 -0.3192 S23 0.1127

REMARK 3 S31 1.0844 S32 -1.4521 S33 -0.1682 REMARK 3 S31 -0.9197 S32 -0.8060 S33 0.2108

REMARK 3 TLS GROUP : 11 REMARK 3 TLS GROUP : 17

REMARK 3 SELECTION: chain 'Β' and (resid 198 through 227 ) REMARK 3 SELECTION: chain 'Β' and (resid 301 through 314 )

REMARK 3 ORIGIN FOR THE GROUP (A): 94.8966 -48.5955 - 2.3933 REMARK 3 ORIGIN FOR THE GROUP (A): 96.0561 -40.1387 -17.0384

REMARK 3 T TENSOR REMARK 3 T TENSOR

REMARK 3 Ti l 0.3729 T22 0.3587 REMARK 3 Ti l 0.5710 T22 0.5758

REMARK 3 T33 0.5199 T12 -0.0317 REMARK 3 T33 0.3773 T12 -0.0341

REMARK 3 T13 0.0514 T23 -0.0067 REMARK 3 T13 -0.0190 T23: 0.0308

REMARK 3 L TENSOR REMARK 3 L TENSOR

REMARK 3 Ll l 3.2456 L22 4.8310 REMARK 3 Ll l 9.0583 L22 4.4916

REMARK 3 L33 3.6015 L12 1.6632 REMARK 3 L33 4.0786 L12 0.9703

REMARK 3 L13 0.0335 L23 -0.3002 REMARK 3 L13 -6.1633 L23 -0.3551

REMARK 3 S TENSOR REMARK 3 S TENSOR

REMARK 3 Sl l 0.0959 S12 -0.1614 S13 -0.6866 REMARK 3 Sl l -0.5655 S12 1.7341 S13 -0.0968

REMARK 3 S21 0.3321 S22 -0.1757 S23 -0.1693 REMARK 3 S21 -0.9309 S22 0.3457 S23 -0.0561

REMARK 3 S31 0.4177 S32 0.1672 S33 0.1094 REMARK 3 S31 0.6964 S32 -1.2850 S33 0.1675

REMARK 3 TLS GROUP : 12 REMARK 3 TLS GROUP : 18

REMARK 3 SELECTION: chain 'Β' and (resid 228 through 242 ) REMARK 3 SELECTION: chain 'Β' and (resid 315 through 324 )

REMARK 3 ORIGIN FOR THE GROUP (A): 112.4208 -51.6896 - 13.1983 REMARK 3 ORIGIN FOR THE GROUP (A): 85.7637 -36.4903 5.1908

REMARK 3 T TENSOR REMARK 3 T TENSOR

REMARK 3 Ti l 0.7790 T22 0.5122 REMARK 3 Ti l 0.9311 T22 0.7813

REMARK 3 T33 1.0026 T12 0.1648 REMARK 3 T33 0.7808 T12 0.0715

REMARK 3 T13 0.1659 T23 -0.1220 REMARK 3 T13 0.1264 T23 -0.2422

REMARK 3 L TENSOR REMARK 3 L TENSOR

REMARK 3 Ll l 3.7366 L22 2.5001 REMARK 3 Ll l 9.5457 L22 5.3768

REMARK 3 L33 0.7851 L12 3.0397 REMARK 3 L33 8.6160 L12 7.1404

REMARK 3 L13 1.3074 L23 1.0241 REMARK 3 L13 -0.7572 L23 -0.6912

REMARK 3 S TENSOR REMARK 3 S TENSOR

REMARK 3 Sl l 0.1534 S12 0.8507 S13 -1.6972 REMARK 3 Sl l 0.9085 S12 -1.4752 S13 1.2802

REMARK 3 S21 -0.4068 S22 0.1129 S23 -0.7964 REMARK 3 S21 2.8252 S22 0.2965 S23 -0.1022

REMARK 3 S31 -0.8144 S32 -0.0429 S33 -0.2444 REMARK 3 S31 -1.1428 S32 0.4070 S33 -1.0872

REMARK 3 TLS GROUP : 13 REMARK 3 TLS GROUP : 19

REMARK 3 SELECTION: chain 'Β' and (resid 243 through 251 ) REMARK 3 SELECTION: chain 'Β' and (resid 325 through 335 )

 ATOM 82 CE1 TYR A 164 116.767 -38.833 4.598 1.00 56.67 C ATOM 127 CZ ARG A 169 110.751 -40.536 5.196 1.00 73.48 C

ANISOU 82 CE1 TYR A 164 8169 8423 4941 2261 409 646 C ANISOU 127 CZ ARG A 169 9892 10168 7859 2342 2580 1598 (

ATOM 83 CZ TYR A 164 115.851 -38.162 5.389 1.00 64.24 C ATOM 128 NHl ARG A 169 111.080 -39.747 6.194 1.00 65.58 N

ANISOU 83 CZ TYR A 164 9364 9432 5611 2538 570 601 C ANISOU 128 NHl ARG A 169 9251 9327 6338 2708 2434 1478

ATOM 84 OH TYR A 164 115.771 -38.464 6.723 1.00 75.84 O ATOM 129 NH2 ARG A 169 109.488 -40.738 4.889 1.00 74.99 N

ANISOU 84 OH TYR A 164 11222 11026 6569 3019 723 722 O ANISOU 129 ΝΉ2 ARG A 169 9827 10208 8459 2186 2847 1697

ATOM 85 CE2 TYR A 164 115.022 -37.192 4.844 1.0049.80 C ATOM 130 C ARG A 169 115.383 -44.385 3.716 1.00 58.53 C

ANISOU 85 CE2 TYR A 164 7404 7535 3982 2375 588 442 C ANISOU 130 C ARG A 169 7942 8201 6094 1998 2023 1935 C

ATOM 86 CD2 TYR A 164 115.119 -36.898 3.498 1.00 41.28 C ATOM 131 O ARG A 169 115.185 -44.908 4.766 1.00 65.30 O

ANISOU 86 CD2 TYR A 164 5982 6338 3363 1939 436 344 C ANISOU 131 O ARG A 169 8993 9016 6800 2265 2206 2100 O

ATOM 87 C TYR A 164 114.639 -39.219 0.879 1.00 34.16 C ATOM 132 N LEU A 170 115.026 -44.935 2.579 1.00 64.83 N

ANISOU 87 C TYR A 164 4349 5193 3439 1204 918 736 C ANISOU 132 N LEU A 170 8415 8816 7401 1645 2099 1934 N

ATOM 88 O TYR A 164 114.787 -40.337 1.363 1.00 44.10 O ATOM 133 CA LEU A 170 114.442 -46.270 2.522 1.00 66.72 C

ANISOU 88 O TYR A 164 5666 6451 4638 1324 1136 956 O ANISOU 133 CA LEU A 170 8536 8788 8027 1561 2373 2135 C

ATOM 89 N ILE A 165 113.460 -38.623 0.795 1.00 38.35 N ATOM 134 CB LEU A 170 113.403 -46.378 1.413 1.00 61.59 C

ANISOU 89 N FLE A 165 4823 5687 4063 1200 1079 695 N ANISOU 134 CB LEU A 170 7554 7930 7916 1209 2420 2026 C

ATOM 90 CA FLE A 165 112.250 -39.226 1.333 1.00 48.87 C ATOM 135 CG LEU A 170 112.508 -45.194 1.087 1.00 71.61 C

ANISOU 90 CA FLE A 165 6130 6986 5453 1340 1550 914 C ANISOU 135 CG LEU A 170 8705 9260 9243 1101 2378 1842 C

ATOM 91 CB ILE A 165 111.073 -38.225 1.292 1.00 50.77 C ATOM 136 CD1 LEU A 170 111.586 -45.585 -0.051 1.00 68.42 C

ANISOU 91 CB FLE A 165 6306 7216 5770 1375 1640 802 C ANISOU 136 CD1 LEU A 170 7995 8624 9378 783 2351 1731 C

ATOM 92 CGI FLE A 165 111.337 -37.082 2.265 1.00 44.29 C ATOM 137 CD2 LEU A 170 111.712 -44.780 2.307 1.00 80.57 C

ANISOU 92 CGI ILE A 165 5812 6519 4499 1678 1458 628 C ANISOU 137 CD2 LEU A 170 10009 10444 10158 1362 2602 1955

ATOM 93 CD1 FLE A 165 111.586 -37.560 3.697 1.00 39.10 C ATOM 138 C LEU A 170 115.515 -47.308 2.240 1.00 69.65 C

ANISOU 93 CD1 ILE A 165 5490 5984 3380 2084 1659 792 C ANISOU 138 C LEU A 170 8919 9103 8441 1559 2294 2235 C

ATOM 94 CG2 FLE A 165 109.747 -38.901 1.620 1.00 36.02 C ATOM 139 O LEU A 170 115.288 -48.508 2.366 1.00 73.24 o

ANISOU 94 CG2 ILE A 165 4283 5283 4121 1452 2162 1048 C ANISOU 139 O LEU A 170 9342 9342 9144 1564 2485 2402 o

ATOM 95 C FLE A 165 111.861 -40.515 0.609 1.00 45.97 C ATOM 140 N FLE A 171 116.680 -46.842 1.825 1.00 62.81 N

ANISOU 95 C ILE A 165 5495 6467 5505 1121 1798 1107 C ANISOU 140 N FLE A 171 8068 8400 7397 1538 1937 2067 N

ATOM 96 O ILE A 165 111.359 -41.459 1.219 1.00 50.30 O ATOM 141 CA FLE A 171 117.687 -47.747 1.310 1.00 54.15 C

ANISOU 96 O FLE A 165 6046 6960 6105 1241 2190 1376 O ANISOU 141 CA ILE A 171 6908 7231 6434 1489 1796 2085 c

ATOM 97 N GLY A 166 112.038 -40.538 -0.695 1.00 44.97 N ATOM 142 CB FLE A 171 117.963 -47.458 -0.177 1.00 52.72 c

ANISOU 97 N GLY A 166 5153 6256 5680 816 1571 972 N ANISOU 142 CB FLE A 171 6448 7015 6569 1155 1551 1813 c

ATOM 98 CA GLY A 166 111.595 -41.651 -1.494 1.0046.42 C ATOM 143 CGI ILE A 171 117.425 -48.598 -1.044 1.00 62.70 c

ANISOU 98 CA GLY A 166 5078 6264 6296 609 1734 1068 C ANISOU 143 CGI FLE A 171 7536 8004 8283 965 1756 1885 c

ATOM 99 C GLY A 166 112.585 -42.674 -1.962 1.00 49.67 C ATOM 144 CD1 ILE A 171 118.507 -49.561 -1.529 1.00 57.89 c

ANISOU 99 C GLY A 166 5480 6621 6769 510 1629 1113 C ANISOU 144 CD1 FLE A 171 6904 7327 7763 989 1642 1893 c

ATOM 100 O GLY A 166 112.254 -43.542 -2.717 1.00 53.06 O ATOM 145 CG2 ILE A 171 119.448 -47.210 -0.425 1.0047.41 c

ANISOU 100 O GLY A 166 5720 6885 7556 335 1676 1125 O ANISOU 145 CG2 FLE A 171 5763 6496 5757 1191 1178 1665 c

ATOM 101 N TYR A 167 113.828 -42.530 -1.579 1.00 50.40 N ATOM 146 C FLE A 171 118.962 -47.701 2.147 1.00 54.13 c

ANISOU 101 N TYR A 167 5773 6844 6533 638 1456 1111 N ANISOU 146 C FLE A 171 7132 7413 6022 1790 1530 2094 c

ATOM 102 CA TYR A 167 114.816 -43.511 -1.956 1.00 48.12 C ATOM 147 O FLE A 171 119.615 -48.719 2.362 1.00 63.95 o

ANISOU 102 CA TYR A 167 5471 6516 6297 591 1379 1168 C ANISOU 147 O FLE A 171 8446 8593 7258 1932 1560 2262 o

ATOM 103 CB TYR A 167 115.468 -43.187 -3.298 1.00 38.31 C ATOM 148 N LEU A 172 119.304 -46.515 2.634 1.0047.71 N

ANISOU 103 CB TYR A 167 4095 5280 5182 373 1082 962 C ANISOU 148 N LEU A 172 6432 6809 4889 1902 1240 1899 N

ATOM 104 CG TYR A 167 116.491 -44.174 -3.702 1.00 31.13 C ATOM 149 CA LEU A 172 120.481 -46.363 3.483 1.00 55.03 c

ANISOU 104 CG TYR A 167 3158 4335 4333 353 1032 1011 C ANISOU 149 CA LEU A 172 7560 7907 5442 2203 906 1855 c

ATOM 105 CD1 TYR A 167 116.136 -45.410 -4.137 1.0048.17 C ATOM 150 CB LEU A 172 120.769 -44.890 3.787 1.00 51.97 c

ANISOU 105 CD1 TYR A 167 5228 6304 6772 296 1215 1103 C ANISOU 150 CB LEU A 172 7228 7691 4825 2239 517 1552 c

ATOM 106 CE1 TYR A 167 117.051 -46.306 -4.499 1.00 29.30 C ATOM 151 CG LEU A 172 121.240 -44.075 2.593 1.00 60.79 c

ANISOU 106 CE1 TYR A 167 2832 3867 4435 312 1174 1135 C ANISOU 151 CG LEU A 172 8021 8805 6273 1871 225 1277 c

ATOM 107 CZ TYR A 167 118.347 -45.996 -4.425 1.00 32.82 C ATOM 152 CD1 LEU A 172 121.711 -42.716 3.066 1.00 63.38 c

ANISOU 107 CZ TYR A 167 3322 4479 4669 384 966 1094 C ANISOU 152 CD1 LEU A 172 8423 9256 6403 1942 -202 998 c

ATOM 108 OH TYR A 167 119.252 -46.919 -4.782 1.00 41.47 O ATOM 153 CD2 LEU A 172 122.343 -44.817 1.861 1.00 56.04 c

ANISOU 108 OH TYR A 167 4392 5536 5827 429 943 1128 O ANISOU 153 CD2 LEU A 172 7197 8175 5919 1760 96 1295 c

ATOM 109 CE2 TYR A 167 118.735 -44.792 -3.976 1.00 33.13 C ATOM 154 C LEU A 172 120.473 -47.183 4.785 1.00 65.71 C

ANISOU 109 CE2 TYR A 167 3411 4700 4478 415 772 1010 C ANISOU 154 C LEU A 172 9263 9274 6429 2632 1112 2153 C

ATOM 110 CD2 TYR A 167 117.812 -43.884 -3.629 1.00 35.52 C ATOM 155 O LEU A 172 121.486 -47.819 5.101 1.00 73.94 O

ANISOU 110 CD2 TYR A 167 3759 5027 4712 401 797 960 C ANISOU 155 O LEU A 172 10359 10336 7397 2788 927 2172 O

ATOM 111 C TYR A 167 115.842 -43.763 -0.887 1.00 37.61 C ATOM 156 N PRO A 173 119.359 -47.157 5.551 1.00 63.91 N

ANISOU 111 C TYR A 167 4374 5314 4602 841 1308 1265 C ANISOU 156 N PRO A 173 9182 8994 6108 2741 1464 2243 N

ATOM 112 O TYR A 167 115.980 -44.841 -0.408 1.00 54.20 O ATOM 157 CA PRO A 173 119.343 -47.849 6.847 1.00 72.40 C

ANISOU 112 O TYR A 167 6559 7357 6679 981 1512 1486 O ANISOU 157 CA PRO A 173 10522 10049 6939 3086 1637 2389 C

ATOM 113 N LEU A 168 116.588 -42.733 -0.580 1.00 44.24 N ATOM 158 CB PRO A 173 117.858 -47.878 7.197 1.00 65.42 C

ANISOU 113 N LEU A 168 5316 6308 5186 905 994 1095 N ANISOU 158 CB PRO A 173 9635 9040 6184 3085 2101 2538 C

ATOM 114 CA LEU A 168 117.719 -42.803 0.289 1.00 39.59 C ATOM 159 CG PRO A 173 117.347 -46.601 6.632 1.00 61.93 C

ANISOU 114 CA LEU A 168 4913 5843 4285 1135 800 1115 C ANISOU 159 CG PRO A 173 9081 8684 5764 2899 1985 2328 C

ATOM 115 CB LEU A 168 118.400 -41.456 0.341 1.0047.60 C ATOM 160 CD PRO A 173 118.106 -46.403 5.343 1.00 64.47 C

ANISOU 115 CB LEU A 168 5966 6970 5148 1134 394 864 C ANISOU 160 CD PRO A 173 9175 9037 6281 2597 1689 2202 C

ATOM 116 CG LEU A 168 119.233 -41.056 -0.857 1.00 44.06 C ATOM 161 C PRO A 173 119.890 -49.271 6.823 1.00 75.75 C

ANISOU 116 CG LEU A 168 5267 6494 4978 839 160 721 C ANISOU 161 C PRO A 173 10928 10333 7519 3125 1751 2598 C

ATOM 117 CD1 LEU A 168 119.778 -39.714 -0.676 1.0040.81 C ATOM 162 O PRO A 173 120.603 -49.661 7.746 1.00 69.85 O

ANISOU 117 CD1 LEU A 168 4872 6139 4496 820 -216 502 C ANISOU 162 O PRO A 173 10408 9657 6476 3430 1634 2625 O

ATOM 118 CD2 LEU A 168 120.319 -42.025 -1.031 1.00 39.25 C ATOM 163 N GLU A 174 119.574 -50.033 5.784 1.00 71.87 N

ANISOU 118 CD2 LEU A 168 4554 5889 4471 830 132 819 C ANISOU 163 N GLU A 174 10180 9635 7494 2829 1952 2717 N

ATOM 119 C LEU A 168 117.433 -43.219 1.695 1.00 51.50 C ATOM 164 CA GLU A 174 119.989 -51.424 5.750 1.00 77.47 C

ANISOU 119 C LEU A 168 6698 7393 5478 1484 1044 1329 C ANISOU 164 CA GLU A 174 10879 10170 8387 2868 2083 2907 C

ATOM 120 O LEU A 168 118.185 -43.944 2.269 1.00 53.79 O ATOM 165 CB GLU A 174 118.806 -52.335 5.433 1.00 70.91 C

ANISOU 120 O LEU A 168 7112 7701 5626 1672 1059 1486 O ANISOU 165 CB GLU A 174 9887 9034 8020 2679 2533 3099 C

ATOM 121 N ARG A 169 116.360 -42.735 2.272 1.00 49.82 N ATOM 166 CG GLU A 174 117.692 -52.247 6.445 1.00 76.28 C

ANISOU 121 N ARG A 169 6594 7196 5139 1604 1255 1355 N ANISOU 166 CG GLU A 174 10687 9682 8616 2845 2871 3235 C

ATOM 122 CA ARG A 169 116.081 -43.062 3.641 1.00 58.82 C ATOM 167 CD GLU A 174 118.102 -52.781 7.800 1.00106.62 C

ANISOU 122 CA ARG A 169 8044 8402 5903 1998 1521 1575 C ANISOU 167 CD GLU A 174 14852 13588 12071 3264 2965 3408 C

ATOM 123 CB ARG A 169 115.277 -41.978 4.323 1.00 62.17 C ATOM 168 OE1 GLU A 174 119.003 -53.649 7.853 1.00116.02 O

ANISOU 123 CB ARG A 169 8633 8916 6074 2189 1601 1480 C ANISOU 168 OE1 GLU A 174 16115 14740 13226 3359 2875 3486 O

ATOM 124 CG ARG A 169 113.825 -42.185 4.234 1.00 66.31 C ATOM 169 OE2 GLU A 174 117.524 -52.331 8.815 1.00111.19 O

ANISOU 124 CG ARG A 169 8984 9327 6885 2097 2077 1642 C ANISOU 169 OE2 GLU A 174 15623 14251 12374 3520 3126 3464 O

ATOM 125 CD ARG A 169 113.106 -40.999 4.735 1.00 71.86 C ATOM 170 C GLU A 174 121.100 -51.675 4.752 1.00 70.07 C

ANISOU 125 CD ARG A 169 9823 10112 7367 2285 2094 1497 C ANISOU 170 C GLU A 174 9776 9235 7613 2735 1778 2820 C

ATOM 126 NE ARG A 169 111.689 -41.138 4.494 1.00 73.35 N ATOM 171 O GLU A 174 121.312 -52.807 4.327 1.00 67.57 O

ANISOU 126 NE ARG A 169 9773 10134 7962 2140 2420 1597 N ANISOU 171 O GLU A 174 9378 8720 7575 2678 1900 2947 O ATOM 172 N LEU A 175 121.815 -50.628 4.370 1.00 66.42 N ATOM 217 CD ARG A 180 128.430 -55.323 8.896 1.00104.25 C

ANISOU 172 N LEU A 175 9245 8981 7009 2700 1375 2597 N ANISOU 217 CD ARG A 180 14944 13973 10694 4509 188 2870 (

ATOM 173 CA LEU A 175 122.786 -50.788 3.303 1.00 68.74 C ATOM 218 NE ARG A 180 129.208 -54.366 9.677 1.00117.14 N

ANISOU 173 CA LEU A 175 9304 9274 7539 2573 1111 2515 C ANISOU 218 NE ARG A 180 16654 15840 12014 4697 -305 2605 N

ATOM 174 CB LEU A 175 123.215 -49.449 2.718 1.00 68.07 c ATOM 219 CZ ARG A 180 129.199 -54.309 11.006 1.00126.76 C

ANISOU 174 CB LEU A 175 9007 9377 7477 2359 733 2150 c ANISOU 219 CZ ARG A 180 18228 17147 12788 5052 -352 2618 C

ATOM 175 CG LEU A 175 124.122 -49.686 1.513 1.00 71.76 c ATOM 220 NH1 ARG A 180 129.938 -53.405 11.636 1.00128.69 N

ANISOU 175 CG LEU A 175 9156 9821 8290 2143 555 1995 c ANISOU 220 ΝΉ1 ARG A 180 18520 17576 12802 5203 -846 2328 N

ATOM 176 CD1 LEU A 175 123.326 -50.325 0.383 1.00 69.95 c ATOM 221 ΝΉ2 ARG A 180 128.459 -55.158 11.705 1.00127.17 N

ANISOU 176 CD1 LEU A 175 8768 9360 8452 1857 862 2024 c ANISOU 221 ΝΉ2 ARG A 180 18580 17087 12651 5265 98 2916 N

ATOM 177 CD2 LEU A 175 124.756 -48.395 1.065 1.00 68.69 c ATOM 222 C ARG A 180 128.144 -58.234 5.012 1.00 87.42 C

ANISOU 177 CD2 LEU A 175 8560 9610 7929 1976 187 1697 c ANISOU 222 C ARG A 180 12093 11064 10059 3799 888 3183

ATOM 178 C LEU A 175 124.015 -51.556 3.759 1.00 65.89 c ATOM 223 O ARG A 180 128.988 -59.127 5.034 1.00 94.84 O

ANISOU 178 C LEU A 175 9011 8949 7076 2807 904 2530 c ANISOU 223 O ARG A 180 13038 11929 11068 3960 791 3231 O

ATOM 179 O LEU A 175 124.388 -52.564 3.158 1.00 69.49 o ATOM 224 N TFFR A 181 126.866 -58.451 4.740 1.00 86.09 N

ANISOU 179 O LEU A 175 9354 9244 7805 2764 986 2621 o ANISOU 224 N THR A 181 11947 10691 10072 3599 1291 3316 N

ATOM 180 N GLN A 176 124.641 -51.066 4.822 1.00 70.35 N ATOM 225 CA THR A 181 126.356 -59.771 4.418 1.00 85.37 C

ANISOU 180 N GLN A 176 9761 9708 7259 3057 615 2413 N ANISOU 225 CA THR A 181 11877 10246 10313 3527 1631 3511

ATOM 181 CA GLN A 176 125.846 -51.681 5.358 1.00 74.29 c ATOM 226 CB TFFR A 181 124.822 -59.762 4.401 1.00 88.62 C

ANISOU 181 CA GLN A 176 10324 10257 7646 3288 362 2398 C ANISOU 226 CB TFFR A 181 12289 10472 10911 3305 2045 3634 (

ATOM 182 CB GLN A 176 126.271 -50.977 6.632 1.00 74.33 C ATOM 227 OG1 TFFR A 181 124.342 -59.442 5.713 1.00 90.82 O

ANISOU 182 CB GLN A 176 10570 10451 7223 3555 52 2239 C ANISOU 227 OG1 THR A 181 12807 10883 10816 3505 2191 3775

ATOM 183 CG GLN A 176 126.088 -49.491 6.565 1.00 81.07 C ATOM 228 CG2 THR A 181 124.259 -61.106 3.970 1.00 79.42 C

ANISOU 183 CG GLN A 176 11365 11450 7989 3441 -207 1973 C ANISOU 228 CG2 TFFR A 181 11085 8901 10192 3176 2351 3791 C

ATOM 184 CD GLN A 176 127.229 -48.750 7.209 1.00106.05 C ATOM 229 C THR A 181 126.907 -60.281 3.085 1.00 91.37 C

ANISOU 184 CD GLN A 176 14535 14768 10990 3576 -765 1684 ANISOU 229 C TFFR A 181 12396 10852 11469 3386 1530 3376 C

ATOM 185 OE1 GLN A 176 128.292 -48.586 6.611 1.00119.42 O ATOM 230 O TFFR A 181 127.056 -61.486 2.880 1.00 99.93 O

ANISOU 185 OE1 GLN A 176 15926 16500 12951 3450 -1110 1538 ANISOU 230 O THR A 181 13515 11672 12782 3429 1646 3478 O

ATOM 186 NE2 GLN A 176 127.025 -48.311 8.445 1.00114.32 N ATOM 231 N TYR A 182 127.221 -59.363 2.179 1.00 86.87 N

ANISOU 186 NE2 GLN A 176 15909 15889 11639 3841 -844 1595 ANISOU 231 N TYR A 182 11584 10443 10978 3238 1318 3139 N

ATOM 187 C GLN A 176 125.631 -53.151 5.654 1.00 71.28 C ATOM 232 CA TYR A 182 127.757 -59.771 0.889 1.00 76.62 ι

ANISOU 187 C GLN A 176 10083 9667 7334 3407 715 2679 C ANISOU 232 CA TYR A 182 10057 9032 10022 3144 1244 2982

ATOM 188 O GLN A 176 126.494 -53.978 5.381 1.00 82.45 O ATOM 233 CB TYR A 182 127.691 -58.644 -0.130 1.00 78.14 C

ANISOU 188 O GLN A 176 11416 11018 8892 3466 614 2715 O ANISOU 233 CB TYR A 182 9988 9383 10317 2933 1128 2754 C

ATOM 189 N ALA A 177 124.472 -53.466 6.219 1.00 79.72 N ATOM 234 CG TYR A 182 128.133 -59.095 -1.500 1.00 64.81 c

ANISOU 189 N ALA A 177 11337 10618 8334 3443 1136 2871 N ANISOU 234 CG TYR A 182 8089 7578 8959 2858 1113 2575 c

ATOM 190 CA ALA A 177 124.161 -54.837 6.594 1.00 86.84 C ATOM 235 CD1 TYR A 182 127.226 -59.678 -2.371 1.00 72.08 c

ANISOU 190 CA ALA A 177 12361 11297 9338 3547 1496 3149 C ANISOU 235 CD1 TYR A 182 9003 8169 10215 2668 1334 2537 c

ATOM 191 CB ALA A 177 122.863 -54.907 7.367 1.00 62.05 C ATOM 236 CE1 TYR A 182 127.611 -60.104 -3.619 1.00 79.90 c

ANISOU 191 CB ALA A 177 9383 8074 6121 3609 1934 3329 C ANISOU 236 CE1 TYR A 182 9852 9055 11451 2640 1306 2327 c

ATOM 192 C ALA A 177 124.083 -55.708 5.354 1.00 83.93 C ATOM 237 CZ TYR A 182 128.930 -59.958 -4.010 1.00 75.04 c

ANISOU 192 C ALA A 177 11746 10671 9473 3283 1647 3217 C ANISOU 237 CZ TYR A 182 9071 8683 10756 2793 1115 2189 c

ATOM 193 O ALA A 177 124.414 -56.887 5.392 1.00 82.55 O ATOM 238 OH TYR A 182 129.326 -60.381 -5.254 1.00 70.06 o

ANISOU 193 O ALA A 177 11613 10320 9433 3367 1751 3366 O ANISOU 238 OH TYR A 182 8325 7977 10316 2797 1125 1973 o

ATOM 194 N ARG A 178 123.633 -55.122 4.252 1.00 74.77 N ATOM 239 CE2 TYR A 182 129.860 -59.388 -3.159 1.00 65.52 c

ANISOU 194 N ARG A 178 10342 9475 8590 2979 1647 3095 N ANISOU 239 CE2 TYR A 182 7811 7793 9290 2944 903 2244 c

ATOM 195 CA ARG A 178 123.541 -55.858 3.000 1.00 77.32 C ATOM 240 CD2 TYR A 182 129.457 -58.962 -1.912 1.00 59.62 c

ANISOU 195 CA ARG A 178 10441 9544 9393 2740 1753 3101 C ANISOU 240 CD2 TYR A 182 7232 7129 8290 2982 873 2419 c

ATOM 196 CB ARG A 178 122.688 -55.099 2.003 1.00 70.71 C ATOM 241 C TYR A 182 129.199 -60.182 1.050 1.00 73.36 c

ANISOU 196 CB ARG A 178 9394 8658 8815 2421 1818 2983 C ANISOU 241 C TYR A 182 9603 8742 9528 3399 970 2927 c

ATOM 197 CG ARG A 178 121.235 -55.179 2.331 1.00 70.83 C ATOM 242 O TYR A 182 129.660 -61.154 0.451 1.00 71.50 o

ANISOU 197 CG ARG A 178 9426 8515 8971 2286 2188 3091 C ANISOU 242 O TYR A 182 9317 8321 9530 3451 998 2904 o

ATOM 198 CD ARG A 178 120.451 -54.248 1.460 1.00 63.52 C ATOM 243 N ASN A 183 129.908 -59.427 1.879 1.00 75.52 N

ANISOU 198 CD ARG A 178 8303 7593 8240 1990 2187 2937 C ANISOU 243 N ASN A 183 9894 9318 9482 3561 682 2880 N

ATOM 199 NE ARG A 178 120.408 -54.682 0.071 1.00 54.03 N ATOM 244 CA ASN A 183 131.330 -59.631 2.092 1.00 69.08 c

ANISOU 199 NE ARG A 178 6879 6161 7488 1733 2161 2833 N ANISOU 244 CA ASN A 183 8979 8648 8621 3787 357 2794 c

ATOM 200 CZ ARG A 178 120.571 -53.870 -0.966 1.00 60.81 ATOM 245 CB ASN A 183 131.906 -58.503 2.939 1.00 64.57 c

ANISOU 200 CZ ARG A 178 7533 7161 8411 1504 1907 2490 C ANISOU 245 CB ASN A 183 8386 8395 7752 3884 -8 2678 c

ATOM 201 ΝΉ1 ARG A 178 120.797 -52.582 -0.759 1.00 62.71 N ATOM 246 CG ASN A 183 132.200 -57.271 2.126 1.00 72.76 c

ANISOU 201 NH1 ARG A 178 7770 7707 8349 1502 1700 2333 N ANISOU 246 CG ASN A 183 9081 9637 8927 3668 -202 2431 c

ATOM 202 NH2 ARG A 178 120.511 -54.344 -2.207 1.00 62.39 N ATOM 247 OD1 ASN A 183 132.154 -57.309 0.899 1.00 77.79 o

ANISOU 202 ΝΉ2 ARG A 178 7557 7179 8969 1301 1857 2304 N ANISOU 247 OD1 ASN A 183 9484 10216 9858 3487 -68 2348 o

ATOM 203 C ARG A 178 124.917 -56.081 2.422 1.00 76.19 C ATOM 248 ND2 ASN A 183 132.519 -56.170 2.801 1.00 75.78 N

ANISOU 203 C ARG A 178 10179 9475 9296 2822 1423 2977 C ANISOU 248 ND2 ASN A 183 9437 10249 9107 3688 -522 2301 N

ATOM 204 O ARG A 178 125.188 -57.090 1.777 1.00 71.95 O ATOM 249 C ASN A 183 131.663 -60.965 2.729 1.00 81.86 C

ANISOU 204 O ARG A 178 9563 8721 9055 2788 1493 3009 O ANISOU 249 C ASN A 183 10818 10075 10210 4039 425 2988 C

ATOM 205 N FLE A 179 125.780 -55.109 2.659 1.00 69.81 N ATOM 250 O ASN A 183 132.805 -61.217 3.100 1.00 79.94 O

ANISOU 205 N FLE A 179 9332 8969 8224 2930 1049 2805 N ANISOU 250 O ASN A 183 10529 9936 9910 4267 152 2949 O

ATOM 206 CA FLE A 179 127.132 -55.157 2.158 1.00 64.05 C ATOM 251 N GLN A 184 130.651 -61.812 2.850 1.00 98.06 N

ANISOU 206 CA ILE A 179 8408 8354 7574 2999 716 2654 C ANISOU 251 N GLN A 184 13084 11832 12344 3986 788 3197 N

ATOM 207 CB FLE A 179 127.735 -53.763 2.131 1.00 52.00 C ATOM 252 CA GLN A 184 130.783 -63.098 3.496 1.00107.67 C

ANISOU 207 CB FLE A 179 6717 7128 5910 2966 332 2414 C ANISOU 252 CA GLN A 184 14534 12827 13549 4203 908 3421 C

ATOM 208 CGI ILE A 179 127.131 -52.974 0.972 1.00 55.85 C ATOM 253 CB GLN A 184 129.845 -63.171 4.689 1.00 93.19 C

ANISOU 208 CGI FLE A 179 6964 7618 6641 2634 404 2275 C ANISOU 253 CB GLN A 184 13011 10950 11449 4270 1158 3675 C

ATOM 209 CD1 ILE A 179 127.736 -51.607 0.785 1.00 57.56 C ATOM 254 CG GLN A 184 130.441 -63.860 5.876 1.00116.71 C

ANISOU 209 CD1 FLE A 179 6966 8087 6818 2505 49 2002 C ANISOU 254 CG GLN A 184 16254 13943 14149 4629 1085 3864 C

ATOM 210 CG2 ILE A 179 129.243 -53.838 2.014 1.00 60.05 C ATOM 255 CD GLN A 184 130.816 -62.879 6.956 1.00130.90 C

ANISOU 210 CG2 FLE A 179 7537 8283 6998 3078 -27 2268 C ANISOU 255 CD GLN A 184 18178 16087 15471 4835 818 3801 C

ATOM 211 C FLE A 179 127.969 -56.090 3.021 1.00 74.21 C ATOM 256 OE1 GLN A 184 130.085 -62.710 7.930 1.00137.40 O

ANISOU 211 C FLE A 179 9866 9625 8705 3289 626 2753 C ANISOU 256 OE1 GLN A 184 19262 16946 15997 4934 1018 3959

ATOM 212 O FLE A 179 128.676 -56.964 2.508 1.00 74.73 O ATOM 257 NE2 GLN A 184 131.951 -62.210 6.784 1.00131.97 N

ANISOU 212 O FLE A 179 9826 9581 8985 3338 601 2760 O ANISOU 257 NE2 GLN A 184 18113 16472 15558 4902 364 3553 N

ATOM 213 N ARG A 180 127.874 -55.897 4.334 1.00 74.18 N ATOM 258 C GLN A 184 130.416 -64.214 2.537 1.00116.25 C

ANISOU 213 N ARG A 180 10139 9729 8319 3502 581 2819 N ANISOU 258 C GLN A 184 15577 13535 15060 4073 1146 3449 C

ATOM 214 CA ARG A 180 128.508 -56.784 5.303 1.00 80.62 C ATOM 259 O GLN A 184 131.260 -65.020 2.146 1.00124.03 O

ANISOU 214 CA ARG A 180 11173 10521 8939 3809 527 2947 C ANISOU 259 O GLN A 184 16506 14415 16206 4215 1038 3401 O

ATOM 215 CB ARG A 180 128.054 -56.445 6.719 1.00 85.92 C ATOM 260 N HIS A 185 129.139 -64.252 2.171 1.00110.66 N

ANISOU 215 CB ARG A 180 12183 11301 9161 4036 574 3023 C ANISOU 260 N HIS A 185 14884 12608 14552 3806 1452 3504 N

ATOM 216 CG ARG A 180 128.933 -55.468 7.468 1.00 91.95 C ATOM 261 C HIS A 185 129.383 -65.406 0.017 1.00 92.33 C

ANISOU 216 CG ARG A 180 12994 12342 9601 4219 84 2787 C ANISOU 261 C HIS A 185 12318 9864 12900 3635 1469 3216 C ATOM 262 O HIS A 185 129.521 -66485 -0.550 1.00 98.64 O ATOM 307 CA LEU A 190 134.820 -61.671 -4.986 1.00 95.91 C

ANISOU 262 O HIS A 185 13138 10359 13983 3667 1510 3178 O ANISOU 307 CA LEU A 190 11460 10243 14740 3450 -524 -1121 C

ATOM 263 CA HIS A 185 128.615 -65.303 1.318 1.00104.80 C ATOM 308 CB LEU A 190 134.059 -60.637 -4.161 1.00 87.74 C

ANISOU 263 CA HIS A 185 14115 11454 14250 3652 1655 3503 C ANISOU 308 CB LEU A 190 10475 9357 13507 3235 -462 -822 C

ATOM 264 CB HIS A 185 127.139 -65.062 1.013 1.00112.81 C ATOM 309 CG LEU A 190 134.612 -59.218 -4.144 1.00 92.31 C

ANISOU 264 CB HIS A 185 15091 12281 15489 3324 1935 3529 C ANISOU 309 CG LEU A 190 10820 10362 13892 3202 -451 -846 C

ATOM 265 CG HIS A 185 126.246 -65.249 2.193 1.00126.75 C ATOM 310 CD1 LEU A 190 133.896 -58.331 -5.146 1.00 86.41 C

ANISOU 265 CG HIS A 185 17047 13979 17133 3339 2220 3828 C ANISOU 310 CD1 LEU A 190 9935 9875 13020 2917 -276 -940 C

ATOM 266 NDl HIS A 185 126.578 -64.797 3.455 1.00131.78 N ATOM 311 CD2 LEU A 190 134.456 -58.672 -2.758 1.00 97.93 C

ANISOU 266 NDl HIS A 185 17870 14903 17298 3592 2178 3979 N ANISOU 311 CD2 LEU A 190 11710 11065 14436 3242 -543 -546 C

ATOM 267 CE1 HIS A 185 125.611 -65.104 4.297 1.00133.99 C ATOM 312 C LEU A 190 136.321 -61.547 -4.736 1.00101.40 C

ANISOU 267 CE1 HIS A 185 18294 15058 17557 3587 2513 4234 ANISOU 312 C LEU A 190 11962 11085 15481 3764 -636 -1224 C

ATOM 268 NE2 HIS A 185 124.662 -65.741 3.630 1.00135.39 N ATOM 313 O LEU A 190 137.007 -60.772 -5.406 1.00107.19 O

ANISOU 268 NE2 HIS A 185 18348 14872 18224 3310 2756 4257 N ANISOU 313 O LEU A 190 12395 12145 16186 3782 -548 -1390 O

ATOM 269 CD2 HIS A 185 125.037 -65.845 2.314 1.00131.80 C ATOM 314 N ARG A 191 136.823 -62.322 -3.775 1.00102.35 N

ANISOU 269 CD2 HIS A 185 17704 14302 18072 3152 2554 3989 ANISOU 314 N ARG A 191 12243 10934 15711 4020 -830 -1108 N

ATOM 270 N TYR A 186 129.888 -64.273 -0.451 1.00 97.02 N ATOM 315 CA ARG A 191 138.241 -62.311 -3.423 1.00 92.68 C

ANISOU 270 N TYR A 186 12866 8573 15423 3009 47 783 N ANISOU 315 CA ARG A 191 10820 9781 14614 4348 -1021 -1202 C

ATOM 271 CA TYR A 186 130.601 -64.247 -1.715 1.00 95.33 C ATOM 316 CB ARG A 191 139.070 -62.902 -4.549 1.00 82.16 C

ANISOU 271 CA TYR A 186 12399 8574 15249 3003 -192 278 C ANISOU 316 CB ARG A 191 9253 8467 13495 4543 -934 -1528 C

ATOM 272 CB TYR A 186 129.839 -63.409 -2.733 1.00 98.17 c ATOM 317 CG ARG A 191 138.862 -64.381 -4.694 1.00 92.03 C

ANISOU 272 CB TYR A 186 12474 9203 15622 2672 -134 91 c ANISOU 317 CG ARG A 191 10784 9297 14886 4699 -989 -1602 C

ATOM 273 CG TYR A 186 128.475 -63.961 -3.053 1.00109.28 c ATOM 318 CD ARG A 191 138.932 -64.798 -6.139 1.00 85.99 C

ANISOU 273 CG TYR A 186 13823 10238 17462 2362 -43 209 c ANISOU 318 CD ARG A 191 9943 8559 14170 4746 -801 -1933 C

ATOM 274 CD1 TYR A 186 128.331 -65.017 -3.935 1.00107.32 c ATOM 319 NE ARG A 191 139.533 -66.117 -6.261 1.00 98.85 N

ANISOU 274 CD1 TYR A 186 13548 9632 17598 2305 -239 -55 c ANISOU 319 NE ARG A 191 11687 9851 16021 5090 -914 -2097 N

ATOM 275 CE1 TYR A 186 127.093 -65.536 -4.236 1.00108.04 c ATOM 320 CZ ARG A 191 140.827 -66.354 -6.078 1.00112.46 C

ANISOU 275 CE1 TYR A 186 13541 9324 18185 2007 -237 30 c ANISOU 320 CZ ARG A 191 13216 11667 17849 5318 -939 -2112 C

ATOM 276 CZ TYR A 186 125.969 -64.996 -3.654 1.00111.82 c ATOM 321 NHl ARG A 191 141.302 -67.586 -6.203 1.00104.32 N

ANISOU 276 CZ TYR A 186 13903 9779 18806 1761 30 414 c ANISOU 321 NHl ARG A 191 12332 10363 16942 5534 -997 -2201 N

ATOM 277 OH TYR A 186 124.734 -65.519 -3.964 1.00113.56 o ATOM 322 NH2 ARG A 191 141.648 -65.361 -5.766 1.00120.30 N

ANISOU 277 OH TYR A 186 13941 9566 19641 1451 18 506 o ANISOU 322 NH2 ARG A 191 13851 13000 18856 5312 -921 -2030 N

ATOM 278 CE2 TYR A 186 126.078 -63.939 -2.768 1.00108.67 c ATOM 323 C ARG A 191 138.706 -60.903 -3.099 1.00 99.97 C

ANISOU 278 CE2 TYR A 186 13559 9758 17974 1843 291 695 c ANISOU 323 C ARG A 191 11480 11061 15441 4282 -1079 -1157 C

ATOM 279 CD2 TYR A 186 127.330 -63.429 -2.471 1.00108.19 c ATOM 324 O ARG A 191 139.677 -60.403 -3.665 1.00100.8; O

ANISOU 279 CD2 TYR A 186 13640 10074 17392 2142 220 576 c ANISOU 324 O ARG A 191 11198 11411 15722 4363 -1053 -1338 O

ATOM 280 C TYR A 186 132.019 -63.730 -1.573 1.00 88.95 c ATOM 325 N GLY A 192 137.979 -60.268 -2.191 1.00 97.78 N

ANISOU 280 C TYR A 186 11556 8110 14130 3307 -379 c ANISOU 325 N GLY A 192 11432 10798 14923 4142 -1134 -901 N

ATOM 281 O TYR A 186 132.646 -63.346 -2.558 1.00 79.91 o ATOM 326 CA GLY A 192 138.250 -58.906 -1.790 1.00 921 C

ANISOU 281 O TYR A 186 10159 7254 12948 3310 -476 -285 O ANISOU 326 CA GLY A 192 10543 10359 14083 4067 -1236 -852 C

ATOM 282 N ASN A 187 132.522 -63.715 -0.344 1.00 94.49 N ATOM 327 C GLY A 192 137.107 -58.429 -0.924 1.00101.10 C

ANISOU 282 N ASN A 187 12515 8757 14629 3581 -431 330 N ANISOU 327 C GLY A 192 12056 11461 14896 3918 -1200 -565 C

ATOM 283 CA ASN A 187 133.897 -63.300 -0.102 1.00100.37 c ATOM 328 O GLY A 192 136.419 -59.231 -0.292 1.00106.23 O

ANISOU 283 CA ASN A 187 13199 9752 15186 3887 -692 148 c ANISOU 328 O GLY A 192 13090 11818 15455 3977 -1160 -356 O

ATOM 284 CB ASN A 187 134.194 -63.283 1.396 1.00107.63 c ATOM 329 N ALA A 193 136.881 -57.124 -0.914 1.00 99.06 N

ANISOU 284 CB ASN A 187 14510 10537 15846 4200 -800 467 c ANISOU 329 N ALA A 193 11682 11476 14479 3733 -1174 -535 N

ATOM 285 CG ASN A 187 135.670 -63.413 1.701 1.00114.91 c ATOM 330 CA ALA A 193 135.786 -56.563 -0.146 1.00 92.70 C

ANISOU 285 CG ASN A 187 15406 11504 16752 4586 -1183 271 c ANISOU 330 CA ALA A 193 11211 10661 13349 3617 -1094 -272 C

ATOM 286 OD1 ASN A 187 136.466 -62.528 1.387 1.00111.24 o ATOM 331 CB ALA A 193 136.239 -56.239 1.268 1.00 85.64 C

ANISOU 286 OD1 ASN A 187 14625 11390 16252 4610 -1357 30 o ANISOU 331 CB ALA A 193 10620 9667 12252 3914 -1438 -133 C

ATOM 287 ND2 ASN A 187 136.045 -64.525 2.327 1.00121.75 N ATOM 332 C ALA A 193 135.260 -55.317 -0.834 1.00 82.52 C

ANISOU 287 ND2 ASN A 187 16583 11983 17693 4893 -1323 390 ANISOU 332 C ALA A 193 9700 9692 11962 3302 -913 -318 C

ATOM 288 C ASN A 187 134.878 -64.206 -0.840 1.00102.41 C ATOM 333 O ALA A 193 136.031 -54.500 -1.331 1.00 84.82 O

ANISOU 288 C ASN A 187 13316 9898 15696 4082 -877 -186 C ANISOU 333 O ALA A 193 9647 10216 12364 3256 -994 -489 O

ATOM 289 O ASN A 187 135.930 -63.760 -1.297 1.00113.67 O ATOM 334 N VAL A 194 133.944 -55.176 -0.876 1.00 67.94 N

ANISOU 289 O ASN A 187 14465 11610 17113 4217 -1016 -463 O ANISOU 334 N VAL A 194 8027 7835 9954 3087 -658 -148 N

ATOM 290 N ASN A 188 134.519 -65.479 -0.963 1.00 93.40 N ATOM 335 CA VAL A 194 133.371 -53.956 -1.400 1.00 69.10 C

ANISOU 290 N ASN A 188 12352 8316 14820 4101 -857 -147 N ANISOU 335 CA VAL A 194 8018 8262 9975 2821 -519 -166 C

ATOM 291 CA ASN A 188 135.336 -66.437 -1.697 1.00101.81 c ATOM 336 CB VAL A 194 131.990 -54.192 -2.040 1.00 63.56 C

ANISOU 291 CA ASN A 188 13336 9222 16127 4308 -1017 -472 c ANISOU 336 CB VAL A 194 7347 7519 9283 2553 -224 -92 C

ATOM 292 CB ASN A 188 134.932 -67.872 -1.346 1.00102.42 c ATOM 337 CGI VAL A 194 131.949 -55.557 -2.694 1.00 58.36 C

ANISOU 292 CB ASN A 188 13733 8706 16476 4384 -1043 -307 c ANISOU 337 CGI VAL A 194 6670 6625 8881 2563 -173 -202 C

ATOM 293 CG ASN A 188 135.496 -68.324 -0.020 1.00110.24 c ATOM 338 CG2 VAL A 194 130.893 -54.095 -1.012 1.00 78.10 C

ANISOU 293 CG ASN A 188 15056 9462 17367 4735 -1177 -19 c ANISOU 338 CG2 VAL A 194 9501 9220 10954 2549 -89 236 C

ATOM 294 OD1 ASN A 188 136.561 -67.874 0.400 1.00114.87 o ATOM 339 C VAL A 194 133.304 -52.956 -0.252 1.00 68.18 C

ANISOU 294 OD1 ASN A 188 15584 10284 17776 5024 -1386 -102 O ANISOU 339 C VAL A 194 8123 8202 9581 2921 -671 -1 C

ATOM 295 ND2 ASN A 188 134.785 -69.225 0.651 1.00 96.05 N ATOM 340 O VAL A 194 133.091 -53.330 0.905 1.00 70.06 O

ANISOU 295 ND2 ASN A 188 13615 7167 15712 4725 -1073 333 N ANISOU 340 O VAL A 194 8749 8231 9640 3145 -738 210 O

ATOM 296 C ASN A 188 135.243 -66.232 -3.202 1.00 84.41 C ATOM 341 N SERA 195 133.521 -51.687 -0.574 1.00 62.31 N

ANISOU 296 C ASN A 188 10844 7225 14004 4133 -947 -860 C ANISOU 341 N SER A 195 7170 7718 8787 2789 -730 -97 N

ATOM 297 O ASN A 188 136.102 -66.672 -3.959 1.00 88.71 O ATOM 342 CA SER A 195 133.480 -50.635 0.426 1.00 66.35 C

ANISOU 297 O ASN A 188 11265 7791 14649 4351 -1030 -1187 O ANISOU 342 CA SER A 195 7899 8274 9039 2890 -925 7 C

ATOM 298 N LEU A 189 134.182 -65.560 -3.625 1.00 92.06 N ATOM 343 CB SER A 195 133.952 -49.319 -0.179 1.00 65.76 C

ANISOU 298 N LEU A 189 11736 8334 14910 3776 -786 -814 N ANISOU 343 CB SER A 195 7486 8453 9046 2711 -1018 -151 C

ATOM 299 CA LEU A 189 133.913 -65.354 -5.041 1.00 95.19 C ATOM 344 OG SER A 195 134.845 -49.562 -1.243 1.00 76.90 O

ANISOU 299 CA LEU A 189 11957 8887 15326 3619 -744 -1159 C ANISOU 344 OG SER A 195 8462 9955 10800 2629 -985 -353 O

ATOM 300 CB LEU A 189 132.409 -65.404 -5.294 1.00 88.17 C ATOM 345 C SER A 195 132.055 -50.507 0.951 1.00 78.03 C

ANISOU 300 CB LEU A 189 11124 7793 14585 3248 -679 -1047 C ANISOU 345 C SER A 195 9723 9700 10227 2841 -653 272 C

ATOM 301 CG LEU A 189 131.920 -64.906 -6.650 1.00 83.74 C ATOM 346 O SERA 195 131.102 -50.967 0.316 1.00 72.71 O

ANISOU 301 CG LEU A 189 10426 7430 13960 3061 -682 -1363 C ANISOU 346 O SER A 195 8980 9006 9641 2634 -332 341 O

ATOM 302 CD1 LEU A 189 132.484 -65.766 -7.773 1.00 81.76 C ATOM 347 N GLN A 196 131.902 -49.867 2.102 1.00 75.77 N

ANISOU 302 CD1 LEU A 189 10252 7028 13785 3290 -829 -1794 C ANISOU 347 N GLN A 196 9804 9369 9615 3051 -789 415 N

ATOM 303 CD2 LEU A 189 130.402 -64.890 -6.692 1.00 78.74 C ATOM 348 CA GLN A 196 130.637 -49.963 2.815 1.00 95.27 C

ANISOU 303 CD2 LEU A 189 9796 6570 13554 2691 -673 -1205 C ANISOU 348 CA GLN A 196 12658 11728 11812 3115 -472 725 C

ATOM 304 C LEU A 189 134.476 -64.020 -5.515 1.00104.41 C ATOM 349 CB GLN A 196 130.886 -50.181 4.307 1.00107.29 C

ANISOU 304 C LEU A 189 12847 10608 16216 3602 -650 -1299 C ANISOU 349 CB GLN A 196 14754 13030 12983 3563 -650 904 C

ATOM 305 O LEU A 189 135.013 -63.908 -6.619 1.00103.93 O ATOM 350 CG GLN A 196 129.989 -51.235 4.926 1.00117.21 C

ANISOU 305 O LEU A 189 12643 10736 16110 3698 -609 -1623 O ANISOU 350 CG GLN A 196 16367 14021 14147 3700 -255 1260 C

ATOM 306 N LEU A 190 134.340 -63.006 -4.669 1.00103.74 N ATOM 351 CD GLN A 196 130.726 -52.107 5.920 1.00131.08 C

ANISOU 306 N LEU A 190 12716 10757 15943 3499 -596 -1038 N ANISOU 351 CD GLN A 196 18557 15502 15747 4122 -492 1348 C

 ATOM 442 C GLY A 207 124.056 -37.913 -17.754 1.00 58.59 C ATOM 487 O SERA 213 131.061 -49.313 -18.911 1.00 91.58 O

ANISOU 442 C GLY A 207 7276 9597 5390 928 529 -725 C ANISOU 487 O SER A 213 11498 12915 10385 -1297 -936 665 O

ATOM 443 O GLY A 207 125.078 -38.220 -17.140 1.00 63.85 o ATOM 488 N MET A 214 129.086 -48.292 -19.251 1.00106.88 N

ANISOU 443 O GLY A 207 7722 10288 6251 886 756 -652 o ANISOU 488 N MET A 214 12792 15761 12056 -1169 -1455 1782 N

ATOM 444 N VAL A 208 122.975 -38.687 -17.787 1.00 52.82 N ATOM 489 CA MET A 214 129.434 -47.781 -20.570 1.00100.93 C

ANISOU 444 N VAL A 208 6568 8734 4765 938 175 -909 N ANISOU 489 CA MET A 214 12223 15322 10803 -1680 -1675 1718 C

ATOM 445 CA VAL A 208 122.959 -39.983 -17.132 1.00 46.21 C ATOM 490 CB MET A 214 128.275 -48.012 -21.537 1.00113.49 C

ANISOU 445 CA VAL A 208 5532 7767 4261 899 82 -1016 c ANISOU 490 CB MET A 214 13386 17726 12008 -2403 -2121 2191 C

ATOM 446 CB VAL A 208 121.832 -40.095 -16.116 1.00 53.16 c ATOM 491 CG MET A 214 127.606 -49.373 -21.387 1.00126.03 C

ANISOU 446 CB VAL A 208 6151 8536 5511 729 -143 -957 c ANISOU 491 CG MET A 214 14750 19473 13662 -2973 -2119 2023 C

ATOM 447 CGI VAL A 208 121.841 -41.481 -15.477 1.00 56.27 c ATOM 492 SD MET A 214 128.517 -50.735 -22.140 1.00157.08 S

ANISOU 447 CGI VAL A 208 6369 8756 6255 698 -195 -1028 c ANISOU 492 SD MET A 214 19295 23060 17327 -4014 -1779 961 S

ATOM 448 CG2 VAL A 208 121.977 -39.015 -15.065 1.00 45.69 c ATOM 493 CE MET A 214 128.777 -51.803 -20.729 1.00105.49 C

ANISOU 448 CG2 VAL A 208 5029 7705 4625 602 25 -701 c ANISOU 493 CE MET A 214 12781 15799 11503 -3486 -1264 575 C

ATOM 449 C VAL A 208 122.828 -41.084 -18.167 1.00 53.32 c ATOM 494 C MET A 214 129.796 -46.296 -20.533 1.00 96.96 C

ANISOU 449 C VAL A 208 6692 8534 5034 1092 -101 -1302 c ANISOU 494 C MET A 214 11883 14720 10237 -1067 -1664 2050 C

ATOM 450 O VAL A 208 121.869 -41.111 -18.931 1.00 64.85 o ATOM 495 O MET A 214 130.165 -45.716 -21.552 1.00 91.46 O

ANISOU 450 O VAL A 208 8364 9894 6382 1171 -443 -1470 o ANISOU 495 O MET A 214 11382 14228 9139 -1387 -1820 2027 O

ATOM 451 N PRO A 209 123.811 -41.992 -18.199 1.00 50.33 N ATOM 496 N ALA A 215 129.681 -45.679 -19.360 1.00111.58 N

ANISOU 451 N PRO A 209 6313 8132 4679 1197 87 -1378 N ANISOU 496 N ALA A 215 13723 16223 12448 -244 -1420 2344 N

ATOM 452 CA PRO A 209 123.884 -43.032 -19.223 1.00 59.62 c ATOM 497 CA ALA A 215 130.025 -44.262 -19.200 1.00107.97 C

ANISOU 452 CA PRO A 209 7803 9175 5673 1441 -50 -1669 c ANISOU 497 CA ALA A 215 13536 15552 11935 326 -1256 2620 C

ATOM 453 CB PRO A 209 125.335 -43.508 -19.131 1.00 60.97 c ATOM 498 CB ALA A 215 129.447 -43.715 -17.907 1.00106.55 C

ANISOU 453 CB PRO A 209 7916 9423 5827 1560 360 -1630 c ANISOU 498 CB ALA A 215 13305 15026 12155 1078 -897 3020 C

ATOM 454 CG PRO A 209 125.688 -43.293 -17.706 1.00 64.35 c ATOM 499 C ALA A 215 131.537 -44.066 -19.224 1.00 92.13 C

ANISOU 454 CG PRO A 209 7903 9901 6644 1317 491 -1396 c ANISOU 499 C ALA A 215 12125 13085 9795 259 -1078 1935 C

ATOM 455 CD PRO A 209 124.975 -42.026 -17.301 1.00 46.90 c ATOM 500 O ALA A 215 132.047 -43.073 -19.736 1.00 79.93 O

ANISOU 455 CD PRO A 209 5604 7786 4430 1128 423 -1206 c ANISOU 500 O ALA A 215 10876 11503 7990 328 -1053 1961 o

ATOM 456 C PRO A 209 122.949 -44.203 -18.973 1.00 53.38 c ATOM 501 N ASP A 216 132.239 -45.022 -18.631 1.00 79.82 N

ANISOU 456 C PRO A 209 6928 8107 5249 1379 -481 -1875 c ANISOU 501 N ASP A 216 10690 11176 8460 143 -935 1394 N

ATOM 457 O PRO A 209 122.583 -44.527 -17.841 1.00 56.65 o ATOM 502 CA ASP A 216 133.684 -45.089 -18.678 1.00 66.06 C

ANISOU 457 O PRO A 209 6987 8430 6109 1162 -528 -1754 o ANISOU 502 CA ASP A 216 9346 9056 6699 6 -783 812 c

ATOM 458 N ASP A 210 122.580 -44.828 -20.081 1.00 58.64 N ATOM 503 CB ASP A 216 134.294 -44.525 -17.389 1.00 65.42 c

ANISOU 458 N ASP A 210 7959 8608 5712 1601 -793 -2183 N ANISOU 503 CB ASP A 216 9539 8543 6774 510 -560 837 c

ATOM 459 CA ASP A 210 121.848 -46.079 -20.114 1.00 79.31 c ATOM 504 CG ASP A 216 135.828 -44.647 -17.340 1.00 70.81 c

ANISOU 459 CA ASP A 210 10558 10893 8683 1592 -1243 -2442 ANISOU 504 CG ASP A 216 10500 8909 7496 342 -456 359 c

ATOM 460 CB ASP A 210 121.899 -46.590 -21.542 1.00 93.89 ATOM 505 OD1 ASP A 216 136.381 -45.682 -17.750 1.00 74.00 o

ANISOU 460 CB ASP A 210 12963 12612 10101 1955 -1507 -2807 ANISOU 505 OD1 ASP A 216 10776 9234 8107 -2 -412 -7 o

ATOM 461 CG ASP A 210 123.154 -46.128 -22.264 1.00106.02 ATOM 506 OD2 ASP A 216 136.479 -43.690 -16.862 1.00 61.37 o

ANISOU 461 CG ASP A 210 14853 14408 11024 2253 -1004 -2753 ANISOU 506 OD2 ASP A 216 9651 7523 6143 540 -362 388 o

ATOM 462 OD2 ASP A 210 123.089 -45.087 -22.957 1.00103.95 ATOM 507 C ASP A 216 133.961 -46.570 -18.809 1.00 67.30 c

ANISOU 462 OD2 ASP A 210 14874 14310 10314 2376 -911 -2680 ANISOU 507 C ASP A 216 9372 9111 7088 -437 -713 365 c

ATOM 463 OD1 ASP A 210 124.210 -46.782 -22.109 1.00100.76 o ATOM 508 O ASP A 216 133.339 -47.379 -18.123 1.00 67.08 o

ANISOU 463 OD1 ASP A 210 14155 13769 10362 2365 -669 -2754 ANISOU 508 O ASP A 216 9086 9061 7340 -358 -680 466 o

ATOM 464 C ASP A 210 122.498 -47.102 -19.192 1.00 82.20 C ATOM 509 N PRO A 217 134.882 -46.941 -19.706 1.00 66.02 N

ANISOU 464 C ASP A 210 10650 11163 9421 1507 -1055 -2384 C ANISOU 509 N PRO A 217 9420 8830 6834 -911 -599 -130 N

ATOM 465 O ASP A 210 121.834 -47.724 -18.363 1.00 68.23 O ATOM 510 CA PRO A 217 135.176 -48.368 -19.827 1.00 64.08 c

ANISOU 465 O ASP A 210 8573 9176 8176 1297 -1239 -2336 O ANISOU 510 CA PRO A 217 9116 8350 6883 -1313 -340 -551 c

ATOM 466 N ASN A 211 123.805 -47.277 -19.353 1.00 90.27 N ATOM 511 CB PRO A 217 135.888 -48.464 -21.173 1.00 48.60 c

ANISOU 466 N ASN A 211 11784 12328 10185 1691 -668 -2371 N ANISOU 511 CB PRO A 217 7463 6347 4654 -1938 -174 -1014 c

ATOM 467 CA ASN A 211 124.582 -48.145 -18.478 1.00 91.11 C ATOM 512 CG PRO A 217 136.568 -47.138 -21.307 1.00 59.06 c

ANISOU 467 CA ASN A 211 11646 12371 10602 1652 -471 -2302 C ANISOU 512 CG PRO A 217 9013 7671 5756 -1645 -285 -928 c

ATOM 468 CB ASN A 211 124.858 -49.495 -19.139 1.00103.18 C ATOM 513 CD PRO A 217 135.602 -46.143 -20.714 1.00 60.33 c

ANISOU 468 CB ASN A 211 13438 13650 12116 1902 -645 -2627 C ANISOU 513 CD PRO A 217 9020 8151 5751 -1145 -614 -321 c

ATOM 469 CG ASN A 211 123.642 -50.394 -19.140 1.00110.52 C ATOM 514 C PRO A 217 136.084 -48.884 -18.709 1.00 63.77 c

ANISOU 469 CG ASN A 211 14359 14191 13442 1793 -1195 -2829 C ANISOU 514 C PRO A 217 9035 7806 7389 -926 -71 -659 c

ATOM 470 OD1 ASN A 211 122.837 -50.366 -20.070 1.00113.40 O ATOM 515 O PRO A 217 136.365 -50.077 -18.673 1.00 75.95 o

ANISOU 470 OD1 ASN A 211 15002 14416 13669 1888 -1603 -3075 O ANISOU 515 O PRO A 217 10495 9060 9303 -1134 241 -919 o

ATOM 471 ND2 ASN A 211 123.496 -51.192 -18.087 1.00109.03 N ATOM 516 N ASN A 218 136.551 -48.011 -17.824 1.00 58.53 N

ANISOU 471 ND2 ASN A 211 13849 13794 13782 1599 -1227 -2715 N ANISOU 516 N ASN A 218 8446 7036 6757 -433 -161 -426 N

ATOM 472 C ASN A 211 125.878 -47.487 -18.027 1.00 86.33 C ATOM 517 CA ASN A 218 137.290 -48.472 -16.651 1.00 57.92 c

ANISOU 472 C ASN A 211 10878 12051 9873 1672 39 -2059 C ANISOU 517 CA ASN A 218 8269 6617 7121 -144 -31 -365 c

ATOM 473 O ASN A 211 126.714 -47.099 -18.843 1.00 78.01 O ATOM 518 CB ASN A 218 138.402 -47.496 -16.269 1.00 51.91 c

ANISOU 473 O ASN A 211 10028 11165 8448 1891 331 -2080 O ANISOU 518 CB ASN A 218 7721 5747 6256 27 -80 -310 c

ATOM 474 N LEU A 212 126.013 -47.361 -16.712 1.00 95.19 N ATOM 519 CG ASN A 218 139.519 -47.476 -17.274 1.00 56.93 c

ANISOU 474 N LEU A 212 10128 14488 11554 495 -1249 3688 N ANISOU 519 CG ASN A 218 8447 6253 6932 -265 99 -655 c

ATOM 475 CA LEU A 212 127.161 -46.730 -16.080 1.00 95.93 C ATOM 520 OD1 ASN A 218 139.944 -48.518 -17.760 1.00 57.84 o

ANISOU 475 CA LEU A 212 10852 13931 11664 946 -919 3289 C ANISOU 520 OD1 ASN A 218 8408 6135 7433 -494 408 -906 o

ATOM 476 CB LEU A 212 127.042 -46.883 -14.567 1.00 93.98 C ATOM 521 ND2 ASN A 218 139.988 -46.277 -17.618 1.00 60.95 N

ANISOU 476 CB LEU A 212 10752 13167 11791 1472 -519 3285 C ANISOU 521 ND2 ASN A 218 9250 6855 7054 -270 -2 -680 N

ATOM 477 CG LEU A 212 128.290 -46.769 -13.704 1.00 80.74 C ATOM 522 C ASN A 218 136.364 -48.698 -15.467 1.00 51.59 c

ANISOU 477 CG LEU A 212 9712 10871 10095 1658 -263 2763 C ANISOU 522 C ASN A 218 7309 5852 6439 178 -128 -14 c

ATOM 478 CD1 LEU A 212 128.974 -45.427 -13.906 1.00 82.58 C ATOM 523 O ASN A 218 136.807 -48.853 -14.335 1.00 51.21 o

ANISOU 478 CD1 LEU A 212 10387 10897 10091 1814 -122 2675 C ANISOU 523 O ASN A 218 7233 5606 6620 413 -112 158 o

ATOM 479 CD2 LEU A 212 127.877 -46.939 -12.263 1.00 76.72 C ATOM 524 N FLE A 219 135.071 -48.695 -15.748 1.00 53.47 N

ANISOU 479 CD2 LEU A 212 9312 9974 9864 1925 90 2733 C ANISOU 524 N FLE A 219 7431 6381 6503 140 -239 141 N

ATOM 480 C LEU A 212 128.426 -47.402 -16.560 1.00101.92 C ATOM 525 CA FLE A 219 134.069 -48.994 -14.747 1.0047.84 c

ANISOU 480 C LEU A 212 12023 14495 12207 434 -987 2476 C ANISOU 525 CA ILE A 219 6537 5699 5942 412 -262 461 c

ATOM 481 O LEU A 212 129.452 -46.763 -16.803 1.00101.04 O ATOM 526 CB FLE A 219 133.148 -47.801 -14.501 1.00 56.94 c

ANISOU 481 O LEU A 212 12333 14146 11913 496 -923 2195 O ANISOU 526 CB FLE A 219 7753 7063 6819 744 -356 889 c

ATOM 482 N SERA 213 128.320 -48.714 -16.706 1.00110.74 N ATOM 527 CGI ILE A 219 133.968 -46.593 -14.070 1.00 53.02 c

ANISOU 482 N SER A 213 13007 15688 13381 -84 -1045 2124 N ANISOU 527 CGI FLE A 219 7676 6368 6099 981 -293 933 c

ATOM 483 CA SER A 213 129.394 -49.551 -17.201 1.00108.19 C ATOM 528 CD1 ILE A 219 133.121 -45.397 -13.681 1.00 52.89 c

ANISOU 483 CA SER A 213 13017 15118 12974 -596 -956 1401 C ANISOU 528 CD1 FLE A 219 7831 6379 5887 1363 -169 1365 c

ATOM 484 CB SER A 213 128.859 -50.970 -17.357 1.00103.95 C ATOM 529 CG2 ILE A 219 132.127 -48.122 -13.426 1.00 52.12 c

ANISOU 484 CB SER A 213 12287 14695 12513 -1179 -922 1174 C ANISOU 529 CG2 FLE A 219 6967 6415 6419 1033 -276 1218 c

ATOM 485 OG SER A 213 127.614 -51.105 -16.692 1.00 91.43 O ATOM 530 C FLE A 219 133.268 -50.179 -15.245 1.00 54.28 c

ANISOU 485 OG SER A 213 10259 13360 11122 -952 -1005 1685 O ANISOU 530 C FLE A 219 7070 6656 6898 54 -221 343 c

ATOM 486 C SER A 213 129.922 -49.042 -18.539 1.00101.82 C ATOM 531 O FLE A 219 132.538 -50.070 -16.227 1.00 49.64 o

ANISOU 486 C SER A 213 12421 14545 11719 -1058 -1124 1227 C ANISOU 531 O FLE A 219 6385 6448 6026 -281 -366 373 o ATOM 532 N ARG A 220 133437 -51.318 -14.578 1.00 52.26 N ATOM 577 C LYS A 224 124.581 -57.612 -6.087 1.00 61.88 C

ANISOU 532 N ARG A 220 6696 6109 7052 60 -22 241 N ANISOU 577 C LYS A 224 6350 6786 10376 1114 1117 2043

ATOM 533 CA ARG A 220 132.825 -52.567 -15.009 1.00 50.66 C ATOM 578 O LYS A 224 125.084 -58.649 -5.677 1.00 79.58 O

ANISOU 533 CA ARG A 220 6322 5932 6995 -359 137 44 C ANISOU 578 O LYS A 224 8721 8686 12830 1012 1274 1843

ATOM 534 CB ARG A 220 133.894 -53.609 -15.309 1.00 63.82 c ATOM 579 N LEU A 225 124.096 -56.673 -5.283 1.00 68.38 N

ANISOU 534 CB ARG A 220 8077 7136 9034 -606 557 -360 c ANISOU 579 N LEU A 225 7268 7563 11151 1526 1203 2402

ATOM 535 CG ARG A 220 134.474 -53.532 -16.697 1.00 76.30 c ATOM 580 CA LEU A 225 123.941 -56.898 -3.853 1.00 68.91

ANISOU 535 CG ARG A 220 9888 8715 10386 -1116 717 -766 c ANISOU 580 CA LEU A 225 7622 7278 11283 1717 1448 2491

ATOM 536 CD ARG A 220 135.968 -53.766 -16.654 1.00 76.49 c ATOM 581 CB LEU A 225 123.782 -55.567 -3.120 1.00 68.40 (

ANISOU 536 CD ARG A 220 9990 8230 10842 -977 1090 -943 c ANISOU 581 CB LEU A 225 7909 7268 10811 1852 1549 2539

ATOM 537 NE ARG A 220 136.386 -54.937 -17.413 1.00 83.48 N ATOM 582 CG LEU A 225 125.045 -54.815 -2.728 1.00 58.28

ANISOU 537 NE ARG A 220 11006 8688 12026 -1449 1725 -1376 ANISOU 582 CG LEU A 225 7121 5890 9132 1795 1397 2308

ATOM 538 CZ ARG A 220 136.970 -56.008 -16.885 1.00 85.77 ATOM 583 CD1 LEU A 225 124.669 -53.663 -1.823 1.00 54.77

ANISOU 538 CZ ARG A 220 11164 8425 13000 -1276 2248 -1366 ANISOU 583 CD1 LEU A 225 7025 5370 8416 1902 1670 2372

ATOM 539 NHl ARG A 220 137.314 -57.031 -17.662 1.00 95.16 N ATOM 584 CD2 LEU A 225 126.007 -55.751 -2.021 1.00 61.54

ANISOU 539 NHl ARG A 220 12547 9173 14437 -1706 2971 -1764 N ANISOU 584 CD2 LEU A 225 7722 6109 9552 1632 1261 2151

ATOM 540 ΝΉ2 ARG A 220 137.210 -56.063 -15.583 1.00 69.97 N ATOM 585 C LEU A 225 122.714 -57.776 -3.604 1.00 76.72 C

ANISOU 540 ΝΉ2 ARG A 220 8857 6328 11400 -687 2084 -911 N ANISOU 585 C LEU A 225 8255 8306 12590 1655 1653 2635

ATOM 541 C ARG A 220 131.885 -53.121 -13.957 1.00 50.13 C ATOM 586 O LEU A 225 121.908 -57.986 -4.513 1.00 83.49 O

ANISOU 541 C ARG A 220 6036 5858 7155 -128 144 315 C ANISOU 586 O LEU A 225 8638 9600 13483 1389 1550 2676

ATOM 542 O ARG A 220 132.194 -53.117 -12.765 1.00 46.16 O ATOM 587 N PRO A 226 122.566 -58.299 -2.374 1.00 78.29 N

ANISOU 542 O ARG A 220 5553 5089 6895 293 190 507 O ANISOU 587 N PRO A 226 8707 8191 12847 1708 1882 2634

ATOM 543 N PHE A 221 130.743 -53.615 -14.410 1.0045.38 N ATOM 588 CA PRO A 226 121.321 -59.007 -2.060 1.00 81.39

ANISOU 543 N PHE A 221 5231 5579 6433 -487 88 349 N ANISOU 588 CA PRO A 226 8775 8586 13562 1694 2134 2814

ATOM 544 CA PHE A 221 129.805 -54.256 -13.516 1.00 51.00 C ATOM 589 CB PRO A 226 121.573 -59.574 -0.659 1.00 75.37 (

ANISOU 544 CA PHE A 221 5715 6286 7377 -344 140 569 C ANISOU 589 CB PRO A 226 8452 7482 12703 1672 2316 2686

ATOM 545 CB PHE A 221 128.479 -54.512 -14.229 1.00 65.56 C ATOM 590 CG PRO A 226 122.683 -58.741 -0.099 1.00 79.28

ANISOU 545 CB PHE A 221 7268 8671 8971 -832 -37 706 C ANISOU 590 CG PRO A 226 9438 7991 12693 1671 2115 2509

ATOM 546 CG PHE A 221 127.575 -55.445 -13.488 1.00 59.67 C ATOM 591 CD PRO A 226 123.544 -58.411 -1.279 1.00 80.52

ANISOU 546 CG PHE A 221 6292 7898 8483 -853 92 818 C ANISOU 591 CD PRO A 226 9497 8278 12818 1631 1832 2408

ATOM 547 CD1 PHE A 221 126.753 -54.972 -12.478 1.00 60.92 C ATOM 592 C PRO A 226 120.129 -58.057 -2.034 1.00 83.17 C

ANISOU 547 CD1 PHE A 221 6222 8136 8790 -322 17 1304 C ANISOU 592 C PRO A 226 8712 9065 13825 1929 2300 3224

ATOM 548 CE1 PHE A 221 125.919 -55.829 -11.786 1.00 58.77 C ATOM 593 O PRO A 226 120.241 -56.911 -1.600 1.00 84.84 O

ANISOU 548 CE1 PHE A 221 5744 7826 8759 -349 159 1402 C ANISOU 593 O PRO A 226 9271 9276 13688 2047 2394 3232

ATOM 549 CZ PHE A 221 125.908 -57.180 -12.102 1.00 58.77 C ATOM 594 N GLN A 227 118.988 -58.552 -2.492 1.00 81.13 >

ANISOU 549 CZ PHE A 221 5788 7703 8841 -922 378 1003 C ANISOU 594 N GLN A 227 7853 9178 13794 1740 2316 3406

ATOM 550 CE2 PHE A 221 126.734 -57.665 -13.109 1.00 65.13 C ATOM 595 CA GLN A 227 117.816 -57.716 -2.663 1.00 87.79

ANISOU 550 CE2 PHE A 221 6873 8370 9503 -1465 529 504 C ANISOU 595 CA GLN A 227 8191 10348 14817 1983 2456 3967

ATOM 551 CD2 PHE A 221 127.558 -56.797 -13.793 1.00 58.19 C ATOM 596 CB GLN A 227 116.797 -58.424 -3.534 1.00 87.19 ι

ANISOU 551 CD2 PHE A 221 6176 7535 8398 -1422 385 417 C ANISOU 596 CB GLN A 227 7349 10919 14861 1497 2230 4131

ATOM 552 C PHE A 221 130.392 -55.567 -13.005 1.00 56.52 C ATOM 597 CG GLN A 227 117.308 -58.689 -4.919 1.00 87.65

ANISOU 552 C PHE A 221 6480 6473 8520 -401 525 293 C ANISOU 597 CG GLN A 227 7247 11452 14602 929 1726 3858

ATOM 553 O PHE A 221 130.897 -56.378 -13.775 1.00 52.12 O ATOM 598 CD GLN A 227 116.409 -59.620 -5.679 1.00 95.42

ANISOU 553 O PHE A 221 6048 5706 8047 -856 828 -112 O ANISOU 598 CD GLN A 227 7657 13039 15559 197 1516 3898

ATOM 554 N LEU A 222 130.321 -55.763 -11.697 1.00 62.61 N ATOM 599 OE1 GLN A 227 115.568 -60.302 -5.092 1.00 88.00 O

ANISOU 554 N LEU A 222 7201 7004 9585 50 579 544 N ANISOU 599 OE1 GLN A 227 6499 12083 14854 98 1744 4006 o

ATOM 555 CA LEU A 222 130.802 -56.987 -11.089 1.00 64.09 C ATOM 600 NE2 GLN A 227 116.570 -59.654 -6.997 1.00 98.48 N

ANISOU 555 CA LEU A 222 7389 6716 10246 75 932 436 C ANISOU 600 NE2 GLN A 227 7835 13979 15603 -410 1088 3808 N

ATOM 556 CB LEU A 222 131.618 -56.685 -9.836 1.00 64.99 C ATOM 601 C GLN A 227 117.172 -57.293 -1.356 1.00 90.29 C

ANISOU 556 CB LEU A 222 7566 6552 10577 585 870 747 C ANISOU 601 C GLN A 227 8902 10264 15140 2216 2954 4135 C

ATOM 557 CG LEU A 222 133.117 -56.490 -10.030 1.00 69.45 C ATOM 602 O GLN A 227 117.273 -57.975 -0.335 1.00 77.69 O

ANISOU 557 CG LEU A 222 8202 6882 11304 656 920 706 C ANISOU 602 O GLN A 227 7658 8284 13578 2191 3201 3924 O

ATOM 558 CD2 LEU A 222 133.673 -57.553 -10.968 1.00 42.04 C ATOM 603 N GLN A 228 116.505 -56.150 -1.414 1.00 77.76 N

ANISOU 558 CD2 LEU A 222 4693 3085 8195 330 1391 348 C ANISOU 603 N GLN A 228 10247 7639 11657 16 3681 2587 N

ATOM 559 CD1 LEU A 222 133.810 -56.551 -8.682 1.00 64.59 C ATOM 604 CA GLN A 228 115.783 -55.635 -0.276 1.00 77.20 C

ANISOU 559 CD1 LEU A 222 7558 6052 10930 997 839 1120 C ANISOU 604 CA GLN A 228 10045 7953 11335 306 3718 2785 C

ATOM 560 C LEU A 222 129.642 -57.889 -10.719 1.00 72.27 C ATOM 605 CB GLN A 228 116.422 -54.346 0.218 1.00 81.32 C

ANISOU 560 C LEU A 222 8266 7798 11397 -84 1061 474 C ANISOU 605 CB GLN A 228 10794 9022 11081 427 3334 2626 C

ATOM 561 O LEU A 222 129.511 -59.002 -11.226 1.00 72.79 O ATOM 606 CG GLN A 228 115.781 -53.786 1.468 1.00 88.52 C

ANISOU 561 O LEU A 222 8350 7698 11609 -531 1403 166 O ANISOU 606 CG GLN A 228 11561 10419 11655 785 3349 2805 C

ATOM 562 N ASP A 223 128.795 -57.393 -9.830 1.00 68.75 N ATOM 607 CD GLN A 228 116.645 -52.741 2.132 1.00 92.39 C

ANISOU 562 N ASP A 223 7710 7534 10878 250 863 841 N ANISOU 607 CD GLN A 228 12171 11497 11436 977 3046 2674 C

ATOM 563 CA ASP A 223 127.782 -58.227 -9.222 1.00 62.67 C ATOM 608 OE1 GLN A 228 117.699 -52.374 1.615 1.00 95.36 O

ANISOU 563 CA ASP A 223 6779 6747 10284 196 1007 937 C ANISOU 608 OE1 GLN A 228 12743 11873 11618 802 2823 2436 O

ATOM 564 CB ASP A 223 128.443 -59.128 -8.175 1.00 69.82 C ATOM 609 NE2 GLN A 228 116.207 -52.258 3.288 1.00 90.21 N

ANISOU 564 CB ASP A 223 7794 7108 11625 434 1289 966 C ANISOU 609 NE2 GLN A 228 11748 11729 10797 1354 3042 2804 N

ATOM 565 CG ASP A 223 127.536 -60.248 -7.702 1.00 79.32 C ATOM 610 C GLN A 228 114.357 -55.380 -0.712 1.00 77.10 C

ANISOU 565 CG ASP A 223 8887 8197 13052 282 1546 956 C ANISOU 610 C GLN A 228 9991 7653 11649 154 3582 2469 C

ATOM 566 OD1 ASP A 223 126.316 -60.185 -7.956 1.00 87.51 O ATOM 611 O GLN A 228 114.115 -54.766 -1.752 1.00 78.09 O

ANISOU 566 OD1 ASP A 223 9744 9603 13901 -81 1503 894 O ANISOU 611 O GLN A 228 10357 7582 11732 -119 3190 1951 O

ATOM 567 OD2 ASP A 223 128.058 -61.195 -7.079 1.00 81.50 O ATOM 612 N THR A 229 113.413 -55.867 0.082 1.00 72.46 N

ANISOU 567 OD2 ASP A 223 9232 8043 13690 496 1775 1063 O ANISOU 612 N THR A 229 9081 7055 11395 366 3933 2803 N

ATOM 568 C ASP A 223 126.687 -57.377 -8.585 1.00 60.35 C ATOM 613 CA THR A 229 112.008 -55.659 -0.211 1.00 86.25 C

ANISOU 568 C ASP A 223 6333 6754 9844 515 814 1362 C ANISOU 613 CA THR A 229 10731 8554 13486 252 3836 2524 C

ATOM 569 O ASP A 223 126.847 -56.172 -8.404 1.00 49.51 O ATOM 614 CB THR A 229 111.200 -56.928 0.020 1.00 98.72 C

ANISOU 569 O ASP A 223 5064 5468 8281 851 655 1589 O ANISOU 614 CB THR A 229 11861 9715 15935 307 4391 2845 C

ATOM 570 N LYS A 224 125.570 -58.014 -8.261 1.00 54.11 N ATOM 615 OG1 THR A 229 112.053 -58.067 -0.143 1.00102.25 O

ANISOU 570 N LYS A 224 5312 6076 9172 394 915 1474 N ANISOU 615 OG1 THR A 229 12180 10020 16652 354 4584 2973 O

ATOM 571 CA LYS A 224 124.482 -57.340 -7.579 1.00 67.24 C ATOM 616 CG2 THR A 229 110.051 -57.005 -0.971 1.00 97.67 C

ANISOU 571 CA LYS A 224 6786 7933 10830 732 879 1925 C ANISOU 616 CG2 THR A 229 11634 9099 16376 6 4216 2305 C

ATOM 572 CB LYS A 224 123.136 -57.840 -8.100 1.00 79.72 C ATOM 617 C THR A 229 111.494 -54.551 0.686 1.00 85.87 C

ANISOU 572 CB LYS A 224 7895 9982 12412 328 833 2063 C ANISOU 617 C THR A 229 10753 9002 12871 490 3627 2545 C

ATOM 573 CG LYS A 224 122.806 -57.387 -9.501 1.00 89.53 C ATOM 618 O THR A 229 111.907 -54.431 1.839 1.00 79.18 O

ANISOU 573 CG LYS A 224 8845 11840 13333 -117 507 2136 C ANISOU 618 O THR A 229 9827 8638 11620 853 3793 2958 O

ATOM 574 CD LYS A 224 122.770 -55.881 -9.551 1.00 91.80 C ATOM 619 N FLE A 230 110.597 -53.732 0.156 1.00 94.96 N

ANISOU 574 CD LYS A 224 9068 12298 13512 380 350 2572 C ANISOU 619 N FLE A 230 12043 10070 13968 322 3254 2082 N

ATOM 575 CE LYS A 224 121.471 -55.372 -10.129 1.00 94.90 C ATOM 620 CA FLE A 230 110.200 -52.537 0.879 1.00105.12 C

ANISOU 575 CE LYS A 224 8831 13364 13862 269 131 3181 C ANISOU 620 CA ILE A 230 13449 11816 14676 512 2984 2013 C

ATOM 576 NZ LYS A 224 121.041 -54.144 -9.407 1.00 96.27 N ATOM 621 C FLE A 230 108.769 -52.585 1.373 1.00107.19 C

ANISOU 576 NZ LYS A 224 8924 13410 14244 1037 329 3763 N ANISOU 621 C FLE A 230 13460 12036 15231 640 3134 2104



 ATOM 802 NE2 GLN A 252 146.693 -56.390 -15.189 1.00 68.03 N ATOM 847 CB LEU A 259 129.008 -47.189 -8.280 1.00 51.44 C ANISOU 802 NE2 GLN A 252 7125 9756 8969 2571 446 756 N ANISOU 847 CB LEU A 259 6653 6638 6253 616 94 698 C

ATOM 803 C GLN A 252 142.609 -53.317 -12.392 1.0049.03 C ATOM 848 CG LEU A 259 129.582 -45.924 -8.894 1.00 62.42 C

ANISOU 803 C GLN A 252 5149 7065 6417 1809 127 765 C ANISOU 848 CG LEU A 259 7963 8116 7639 509 -3 585 C

ATOM 804 O GLN A 252 142.416 -52.103 -12.390 1.00 50.15 O ATOM 849 CD1 LEU A 259 130.145 -45.051 -7.797 1.00 65.76 C

ANISOU 804 O GLN A 252 5230 7275 6550 1631 71 738 O ANISOU 849 CD1 LEU A 259 8361 8664 7959 560 -137 559 C

ATOM 805 N ARG A 253 142.009 -54.149 -11.556 1.00 60.02 N ATOM 850 CD2 LEU A 259 130.663 -46.299 -9.890 1.00 58.33 C

ANISOU 805 N ARG A 253 6702 8320 7783 1901 121 819 N ANISOU 850 CD2 LEU A 259 7347 7613 7202 506 6 556 C

ATOM 806 CA ARG A 253 141.120 -53.659 -10.522 1.00 65.27 C ATOM 851 C LEU A 259 126.549 -46.860 -8.103 1.00 50.61 C

ANISOU 806 CA ARG A 253 7476 8942 8380 1815 49 852 C ANISOU 851 C LEU A 259 6667 6408 6155 508 208 730 C

ATOM 807 CB ARG A 253 140.506 -54.822 -9.759 1.00 68.74 C ATOM 852 O LEU A 259 126.047 -47.780 -8.747 1.0048.96 O

ANISOU 807 CB ARG A 253 8087 9215 8815 1955 97 951 C ANISOU 852 O LEU A 259 6462 6065 6076 476 299 745 O

ATOM 808 CG ARG A 253 139.560 -54.393 -8.663 1.00 74.55 C ATOM 853 N GLU A 260 126.016 -45.646 -8.054 1.00 44.73 N

ANISOU 808 CG ARG A 253 8938 9924 9462 1901 50 1011 C ANISOU 853 N GLU A 260 5934 5718 5344 433 155 663 N

ATOM 809 CD ARG A 253 138.892 -55.606 -8.071 1.00 78.34 C ATOM 854 CA GLU A 260 124.886 -45.318 -8.905 1.00 43.78 C

ANISOU 809 CD ARG A 253 9579 10215 9973 2033 145 1143 C ANISOU 854 CA GLU A 260 5822 5521 5290 311 203 611 C

ATOM 810 NE ARG A 253 138.380 -56.489 -9.114 1.00 78.20 N ATOM 855 CB GLU A 260 123.586 -45.918 -8.360 1.0044.32 C

ANISOU 810 NE ARG A 253 9633 9970 10108 2006 274 1096 N ANISOU 855 CB GLU A 260 5940 5506 5392 331 312 705 C

ATOM 811 CZ ARG A 253 137.801 -57.662 -8.881 1.00 79.41 C ATOM 856 CG GLU A 260 123.180 -45.451 -6.976 1.00 47.56 C

ANISOU 811 CZ ARG A 253 9909 9895 10369 2097 376 1191 C ANISOU 856 CG GLU A 260 6406 6003 5659 429 314 786 C

ATOM 812 NHl ARG A 253 137.662 -58.092 -7.635 1.00 65.59 N ATOM 857 CD GLU A 260 122.004 -46.249 -6.430 1.00 73.21 C ANISOU 812 NHl ARG A 253 8225 8125 8570 2232 389 1375 N ANISOU 857 CD GLU A 260 9682 9169 8967 467 461 929 C

ATOM 813 NH2 ARG A 253 137.363 -58.404 -9.896 1.00 73.08 N ATOM 858 OE1 GLU A 260 122.096 -47.496 -6.404 1.00 87.23 O ANISOU 813 ΝΉ2 ARG A 253 9157 8882 9728 2063 465 1100 N ANISOU 858 OE1 GLU A 260 11446 10836 10860 505 551 1032 O

ATOM 814 C ARG A 253 141.880 -52.757 -9.557 1.00 46.24 C ATOM 859 OE2 GLU A 260 120.985 -45.632 -6.057 1.00 81.40 O

ANISOU 814 C ARG A 253 4925 6733 5911 1814 -113 864 C ANISOU 859 OE2 GLU A 260 10740 10236 9952 457 493 943 O

ATOM 815 O ARG A 253 142.989 -53.072 -9.142 1.00 51.02 O ATOM 860 C GLU A 260 124.747 -43.823 -9.127 1.00 49.13 C

ANISOU 815 O ARG A 253 5403 7467 6516 1966 -177 899 O ANISOU 860 C GLU A 260 6493 6268 5908 230 120 519 C

ATOM 816 N ALA A 254 141.276 -51.632 -9.204 1.00 53.21 N ATOM 861 O GLU A 260 125.290 -43.009 -8.376 1.00 47.87 O

ANISOU 816 N ALA A 254 5826 7640 6751 1649 -189 818 N ANISOU 861 O GLU A 260 6333 6197 5659 268 26 494 O

ATOM 817 CA ALA A 254 141.905 -50.708 -8.279 1.00 61.18 C ATOM 862 N TYR A 261 124.029 -43.484 -10.191 1.00 47.32 N

ANISOU 817 CA ALA A 254 6707 8820 7718 1639 -368 786 C ANISOU 862 N TYR A 261 6253 5991 5736 127 147 461 N

ATOM 818 CB ALA A 254 142.315 -49.441 -8.997 1.0049.86 C ATOM 863 CA TYR A 261 123.708 -42.107 -10.503 1.0040.20 C

ANISOU 818 CB ALA A 254 5099 7459 6385 1441 -409 699 C ANISOU 863 CA TYR A 261 5350 5125 4798 54 92 397 C

ATOM 819 C ALA A 254 140.954 -50.387 -7.142 1.00 66.62 C ATOM 864 CB TYR A 261 123.388 -41.964 -11.979 1.00 42.64 C

ANISOU 819 C ALA A 254 7549 9484 8279 1637 -441 797 C ANISOU 864 CB TYR A 261 5627 5405 5168 -29 120 344 C

ATOM 820 O ALA A 254 141.312 -49.697 -6.194 1.00 69.58 O ATOM 865 CG TYR A 261 124.596 -41.918 -12.869 1.00 50.21 C

ANISOU 820 O ALA A 254 7858 9996 8584 1664 -609 751 O ANISOU 865 CG TYR A 261 6518 6404 6155 -42 101 323 C

ATOM 821 N GLY A 255 139.730 -50.881 -7.255 1.00 61.93 N ATOM 866 CD1 TYR A 261 125.237 -40.711 -13.125 1.00 41.41 C

ANISOU 821 N GLY A 255 7151 8721 7660 1612 -316 848 N ANISOU 866 CD1 TYR A 261 5359 5336 5038 -88 48 312 C

ATOM 822 CA GLY A 255 138.712 -50.586 -6.273 1.00 52.05 C ATOM 867 CE1 TYR A 261 126.336 -40.652 -13.944 1.00 49.19 C

ANISOU 822 CA GLY A 255 6044 7443 6289 1611 -347 878 C ANISOU 867 CE1 TYR A 261 6262 6365 6062 -97 55 322 C

ATOM 823 C GLY A 255 137.405 -51.265 -6.611 1.00 45.40 C ATOM 868 CZ TYR A 261 126.815 -41.813 -14.522 1.00 46.48 C

ANISOU 823 C GLY A 255 5381 6393 5478 1570 -180 945 C ANISOU 868 CZ TYR A 261 5892 6033 5734 -41 107 323 C

ATOM 824 0 GLY A 255 137.177 -51.692 -7.741 1.00 48.88 O ATOM 869 0H TYR A 261 127.917 -41.749 -15.339 1.00 56.84 O

ANISOU 824 O GLY A 255 5831 6705 6035 1494 -69 918 O ANISOU 869 OH TYR A 261 7115 7409 7072 -29 129 342 O

ATOM 825 N THR A 256 136.545 -51.353 -5.611 1.00 51.64 N ATOM 870 CE2 TYR A 261 126.195 -43.031 -14.284 1.00 50.48 C

ANISOU 825 N THR A 256 6301 7158 6163 1631 -168 1029 N ANISOU 870 CE2 TYR A 261 6454 6477 6248 8 144 310 C

ATOM 826 CA THR A 256 135.270 -52.018 -5.751 1.00 61.33 C ATOM 871 CD2 TYR A 261 125.091 -43.077 -13.460 1.00 50.53 C

ANISOU 826 CA THR A 256 7675 8183 7442 1596 -11 1114 C ANISOU 871 CD2 TYR A 261 6531 6427 6242 -1 145 319 C

ATOM 827 CB THR A 256 135.332 -53.424 -5.158 1.00 63.03 C ATOM 872 C TYR A 261 122.494 -41.680 -9.705 1.0041.89 C

ANISOU 827 CB THR A 256 7965 8308 7677 1805 88 1295 C ANISOU 872 C TYR A 261 5626 5336 4955 72 112 417 C

ATOM 828 OG1 THR A 256 136.433 -54.136 -5.732 1.00 74.47 O ATOM 873 O TYR A 261 121.621 -42.488 -9.412 1.00 43.11 O ANISOU 828 OG1 THR A 256 9328 9754 9214 1895 89 1282 O ANISOU 873 O TYR A 261 5802 5441 5136 98 199 480 O

ATOM 829 CG2 THR A 256 134.056 -54.173 -5.430 1.00 57.25 C ATOM 874 N ALA A 262 122.440 -40.403 -9.354 1.00 42.04 N ANISOU 829 CG2 THR A 256 7352 7328 7073 1743 257 1377 C ANISOU 874 N ALA A 262 5665 5399 4911 61 37 366 N

ATOM 830 C THR A 256 134.277 -51.194 -4.963 1.00 61.39 C ATOM 875 CA ALA A 262 121.255 -39.871 -8.705 1.00 38.91 C

ANISOU 830 C THR A 256 7765 8230 7328 1545 -39 1120 C ANISOU 875 CA ALA A 262 5325 5010 4449 91 59 372 C

ATOM 831 O THR A 256 134.575 -50.783 -3.850 1.00 69.11 O ATOM 876 CB ALA A 262 121.563 -38.572 -8.003 1.00 34.70 C

ANISOU 831 O THR A 256 8744 9370 8143 1669 -146 1141 O ANISOU 876 CB ALA A 262 4821 4526 3838 122 -53 296 C

ATOM 832 N CYS A 257 133.103 -50.935 -5.524 1.00 53.53 N ATOM 877 C ALA A 262 120.181 -39.662 -9.763 1.00 38.08 C

ANISOU 832 N CYS A 257 6836 7103 6401 1382 45 1088 N ANISOU 877 C ALA A 262 5205 4853 4410 4 112 351 C

ATOM 833 CA CYS A 257 132.154 -50.096 -4.807 1.00 49.19 C ATOM 878 O ALA A 262 120.383 -38.933 -10.729 1.00 31.85 O

ANISOU 833 CA CYS A 257 6357 6600 5734 1342 23 1088 C ANISOU 878 O ALA A 262 4391 4056 3656 -66 74 298 O

ATOM 834 CB CYS A 257 132.606 -48.629 -4.828 1.0046.30 C ATOM 879 N THR A 263 119.035 -40.303 -9.570 1.00 37.56 N

ANISOU 834 CB CYS A 257 5910 6383 5297 1245 -145 922 C ANISOU 879 N THR A 263 5144 4758 4368 19 202 404 N

ATOM 835 SG CYS A 257 132.342 -47.808 -6.413 1.00 61.31 S ATOM 880 CA THR A 263 117.941 -40.260 -10.543 1.00 39.32 C

ANISOU 835 SG CYS A 257 7749 8198 7347 985 -130 775 S ANISOU 880 CA THR A 263 5334 4942 4665 -52 241 373 C

ATOM 836 C CYS A 257 130.722 -50.188 -5.315 1.00 49.36 C ATOM 881 CB THR A 263 116.840 -41.265 -10.170 1.00 41.91 C

ANISOU 836 C CYS A 257 6456 6449 5849 1204 154 1105 C ANISOU 881 CB THR A 263 5635 5220 5071 -40 346 446 C

ATOM 837 O CYS A 257 130.464 -50.511 -6.479 1.0041.68 O ATOM 882 OG1 THR A 263 116.357 -40.986 -8.846 1.00 38.62 O

ANISOU 837 O CYS A 257 5464 5339 5031 1082 217 1043 O ANISOU 882 OG1 THR A 263 5259 4852 4562 52 392 527 O

ATOM 838 N VAL A 258 129.798 -49.885 -4.409 1.00 36.44 N ATOM 883 CG2 THR A 263 117.401 -42.674 -10.235 1.00 24.77 C

ANISOU 838 N VAL A 258 4900 4840 4107 1242 185 1180 N ANISOU 883 CG2 THR A 263 3436 2975 3000 -37 392 491 C

ATOM 839 CA VAL A 258 128.404 -49.750 -4.766 1.00 44.98 C ATOM 884 C THR A 263 117.307 -38.897 -10.867 1.00 29.26 C

ANISOU 839 CA VAL A 258 6032 5793 5264 1110 289 1187 C ANISOU 884 C THR A 263 4076 3696 3344 -74 198 318 C

ATOM 840 CB VAL A 258 127.488 -49.987 -3.570 1.0049.65 C ATOM 885 O THR A 263 116.885 -38.682 -12.006 1.00 45.79 O

ANISOU 840 CB VAL A 258 6708 6398 5758 1231 388 1362 C ANISOU 885 O THR A 263 6137 5781 5481 -129 192 274 O

ATOM 841 CG2 VAL A 258 127.825 -51.324 -2.933 1.00 46.49 C ATOM 886 N PRO A 264 117.205 -37.985 -9.877 1.00 37.40 N ANISOU 841 CG2 VAL A 258 6338 5941 5388 1417 494 1572 C ANISOU 886 N PRO A 264 5161 4766 4282 -13 164 315 N

ATOM 842 CGI VAL A 258 126.033 -49.959 -4.008 1.00 43.15 C ATOM 887 CA PRO A 264 116.598 -36.690 -10.218 1.00 39.64 C ANISOU 842 CGI VAL A 258 5908 5429 5058 1086 507 1377 C ANISOU 887 CA PRO A 264 5464 5053 4544 -26 125 262 C

ATOM 843 C VAL A 258 128.223 -48.350 -5.319 1.00 48.92 C ATOM 888 CB PRO A 264 116.688 -35.905 -8.907 1.0041.04 C

ANISOU 843 C VAL A 258 6498 6361 5728 950 184 1008 C ANISOU 888 CB PRO A 264 5709 5266 4617 69 77 238 C

ATOM 844 O VAL A 258 128.511 -47.352 -4.656 1.00 48.72 O ATOM 889 CG PRO A 264 116.664 -36.968 -7.843 1.00 40.43 C

ANISOU 844 O VAL A 258 6469 6486 5557 985 64 945 O ANISOU 889 CG PRO A 264 5644 5235 4483 156 143 316 C

ATOM 845 N LEU A 259 127.750 -48.290 -6.551 1.0045.19 N ATOM 890 CD PRO A 264 117.445 -38.104 -8.423 1.00 32.06 C

ANISOU 845 N LEU A 259 6001 5773 5396 785 225 922 N ANISOU 890 CD PRO A 264 4534 4138 3507 96 165 355 C

ATOM 846 CA LEU A 259 127.833 -47.072 -7.316 1.00 45.45 C ATOM 891 C PRO A 264 117.315 -35.911 -11.322 1.00 36.77 C

ANISOU 846 CA LEU A 259 5987 5860 5422 644 137 771 C ANISOU 891 C PRO A 264 5083 4663 4224 -97 63 218 C



 ATOM 1072 N GLN A 287 120.105 -25.439 -11.348 1.00 42.68 N ATOM 1117 SG CYS A 292 125.052 -31.770 -7.150 1.00 80.54 S

ANISOU 1072 N GLN A 287 6028 4942 5247 -6 474 -575 N ANISOU 1117 SG CYS A 292 9573 10925 10105 -177 -314 -893 S ATOM 1073 CA GLN A 287 119.291 -26.262 -10.480 1.00 37.21 C ATOM 1118 C CYS A 292 123.891 -30.465 -3.413 1.0041.93 C ANISOU 1073 CA GLN A 287 5215 4375 4548 215 479 -566 C ANISOU 1118 C CYS A 292 5622 5847 4463 238 -425 -1018 C ATOM 1074 CB GLN A 287 117.971 -26.641 -11.141 1.00 54.31 C ATOM 1119 O CYS A 292 124.062 -31.168 -2.418 1.00 46.09 O ANISOU 1074 CB GLN A 287 7209 6642 6785 467 544 -418 C ANISOU 1119 O CYS A 292 6199 6508 4804 438 -495 -968 o ATOM 1075 CG GLN A 287 116.986 -25.494 -11.232 1.0040.90 C ATOM 1120 N ARG A 293 123.844 -29.141 -3.365 1.00 51.13 N ANISOU 1075 CG GLN A 287 5760 4769 5013 722 665 -325 C ANISOU 1120 N ARG A 293 7060 6826 5541 109 -466 -1183 N ATOM 1076 CD GLN A 287 116.608 -24.946 -9.871 1.00 49.59 C ATOM 1121 CA ARG A 293 123.970 -28.419 -2.107 1.00 52.73 C ANISOU 1076 CD GLN A 287 7125 5720 5995 902 776 -368 C ANISOU 1121 CA ARG A 293 7666 6963 5407 193 -621 -1367 c ATOM 1077 OE1 GLN A 287 116.041 -25.657 -9.041 1.00 57.21 O ATOM 1122 CB ARG A 293 123.996 -26.918 -2.355 1.00 50.13 c ANISOU 1077 OE1 GLN A 287 7942 6821 6973 1052 840 -330 O ANISOU 1122 CB ARG A 293 7634 6338 5075 -19 -665 -1569 c ATOM 1078 NE2 GLN A 287 116.924 -23.676 -9.632 1.00 61.68 N ATOM 1123 CG ARG A 293 125.325 -26.421 -2.858 1.00 66.91 c ANISOU 1078 NE2 GLN A 287 9086 6949 7401 895 816 -445 N ANISOU 1123 CG ARG A 293 9563 8464 7394 -467 -940 -1736 c ATOM 1079 C GLN A 287 120.053 -27.503 -10.052 1.00 39.52 C ATOM 1124 CD ARG A 293 125.309 -24.922 -3.035 1.00 90.67 c

ANISOU 1079 C GLN A 287 5240 4876 4898 91 369 -630 C ANISOU 1124 CD ARG A 293 12931 11099 10421 -696 -963 -1917 c

ATOM 1080 O GLN A 287 119.861 -28.007 -8.952 1.00 51.16 O ATOM 1125 NE ARG A 293 124.939 -24.540 -4.394 1.00102.36 N

ANISOU 1080 O GLN A 287 6716 6400 6322 198 365 -645 O ANISOU 1125 NE ARG A 293 14300 12418 12173 -816 -708 -1754 N ATOM 1081 N ALA A 288 120.920 -27.994 -10.927 1.00 38.41 N ATOM 1126 CZ ARG A 293 124.160 -23.508 -4.694 1.00106.89 C

ANISOU 1081 N ALA A 288 4893 4860 4842 -91 305 -647 N ANISOU 1126 CZ ARG A 293 15243 12642 12728 -754 -526 -1751 C ATOM 1082 CA ALA A 288 121.717 -29.174 -10.602 1.0042.79 C ATOM 1127 NHl ARG A 293 123.882 -23.231 -5.962 1.00103.74 N ANISOU 1082 CA ALA A 288 5199 5604 5457 -162 209 -698 C ANISOU 1127 NHl ARG A 293 14732 12141 12544 -831 -319 -1573 N ATOM 1083 CB ALA A 288 122.464 -29.677 -11.811 1.00 40.86 C ATOM 1128 ΝΉ2 ARG A 293 123.658 -22.755 -3.725 1.00113.36 N ANISOU 1083 CB ALA A 288 4738 5495 5291 -272 199 -698 C ANISOU 1128 ΝΉ2 ARG A 293 16574 13216 13281 -567 -547 -1922 N

ATOM 1084 C ALA A 288 122.692 -28.881 -9.469 1.0049.91 C ATOM 1129 C ARG A 293 122.848 -28.760 -1.131 1.00 58.02 c

ANISOU 1084 C ALA A 288 6183 6500 6279 -291 94 -813 C ANISOU 1129 C ARG A 293 8611 7630 5806 613 -395 -1231 c

ATOM 1085 O ALA A 288 122.952 -29.733 -8.618 1.0042.56 O ATOM 1130 O ARG A 293 123.069 -28.895 0.075 1.00 57.30 o

ANISOU 1085 O ALA A 288 5158 5692 5322 -218 14 -831 O ANISOU 1130 O ARG A 293 8764 7634 5374 807 -518 -1297 o

ATOM 1086 N LYS A 289 123.234 -27.669 -9.467 1.0042.44 N ATOM 1131 N THR A 294 121.638 -28.891 -1.660 1.00 48.76 N

ANISOU 1086 N LYS A 289 5428 5399 5296 -487 66 -888 N ANISOU 1131 N THR A 294 7381 6368 4776 764 -60 -1030 N ATOM 1087 CA LYS A 289 124.145 -27.260 -8.415 1.00 46.34 C ATOM 1132 CA THR A 294 120.489 -29.133 -0.811 1.0044.14 c ANISOU 1087 CA LYS A 289 6015 5872 5719 -652 -111 -1043 C ANISOU 1132 CA THR A 294 6996 5786 3991 1149 227 -858 c

ATOM 1088 CB LYS A 289 124.819 -25.943 -8.764 1.00 60.14 C ATOM 1133 CB THR A 294 119.174 -28.883 -1.542 1.0047.37 c ANISOU 1088 CB LYS A 289 7921 7405 7524 -968 -136 -1117 C ANISOU 1133 CB THR A 294 7308 6081 4610 1257 550 -686 c ATOM 1089 CG LYS A 289 125.754 -26.015 -9.944 1.00 74.27 C ATOM 1134 OGl THR A 294 119.208 -27.588 -2.147 1.00 51.55 o ANISOU 1089 CG LYS A 289 9406 9313 9500 -1217 -79 -1036 C ANISOU 1134 OGl THR A 294 8025 6392 5167 1127 496 -861 o ATOM 1090 CD LYS A 289 126.266 -24.628 -10.259 1.00 80.93 C ATOM 1135 CG2 THR A 294 118.002 -28.957 -0.560 1.00 41.42 c ANISOU 1090 CD LYS A 289 10445 9874 10431 -1548 -47 -1057 C ANISOU 1135 CG2 THR A 294 6750 5347 3641 1671 887 -503 c ATOM 1091 CE LYS A 289 127.138 -24.608 -11.492 1.00 84.18 C ATOM 1136 C THR A 294 120.522 -30.556 -0.287 1.00 40.40 c ANISOU 1091 CE LYS A 289 10566 10400 11019 -1781 96 -913 C ANISOU 1136 C THR A 294 6331 5516 3504 1305 285 -634 c ATOM 1092 NZ LYS A 289 127.295 -23.213 -11.996 1.00 88.82 N ATOM 1137 O THR A 294 120.199 -30.820 0.870 1.00 50.45 o ANISOU 1092 NZ LYS A 289 11424 10629 11694 -2052 226 -843 N ANISOU 1137 O THR A 294 7849 6856 4462 1609 400 -537 o

ATOM 1093 C LYS A 289 123.386 -27.105 -7.106 1.00 49.67 C ATOM 1138 N LEU A 295 120.925 -31.472 -1.153 1.00 37.85 N

ANISOU 1093 C LYS A 289 6739 6201 5933 -419 -128 -1100 C ANISOU 1138 N LEU A 295 5607 5269 3506 1119 223 -543 N

ATOM 1094 O LYS A 289 123.873 -27.471 -6.037 1.00 56.99 O ATOM 1139 CA LEU A 295 121.016 -32.873 -0.773 1.0048.68 c ANISOU 1094 O LYS A 289 7684 7237 6732 -390 -291 -1195 O ANISOU 1139 CA LEU A 295 6813 6765 4920 1251 276 -325 c

ATOM 1095 N LEU A 290 122.186 -26.551 -7.206 1.00 40.29 N ATOM 1140 CB LEU A 295 121.273 -33.752 -1.993 1.00 38.11 c

ANISOU 1095 N LEU A 290 5789 4832 4688 -212 51 -1027 N ANISOU 1140 CB LEU A 295 5068 5429 3985 1047 245 -265 c ATOM 1096 CA LEU A 290 121.362 -26.305 -6.037 1.00 38.30 C ATOM 1141 CG LEU A 295 121.290 -35.246 -1.706 1.0043.40 c ANISOU 1096 CA LEU A 290 5843 4490 4220 69 117 -1054 C ANISOU 1141 CG LEU A 295 5599 6135 4756 1181 324 -33 c ATOM 1097 CB LEU A 290 120.198 -25.388 -6.399 1.00 36.13 C ATOM 1142 CD1 LEU A 295 119.971 -35.656 -1.068 1.00 50.64 c ANISOU 1097 CB LEU A 290 5815 3989 3923 275 326 -975 C ANISOU 1142 CD1 LEU A 295 6601 6969 5671 1391 678 250 c ATOM 1098 CG LEU A 290 119.167 -25.024 -5.338 1.00 52.76 C ATOM 1143 CD2 LEU A 295 121.527 -36.018 -2.993 1.0040.05 c ANISOU 1098 CG LEU A 290 8237 6000 5807 648 486 -967 C ANISOU 1143 CD2 LEU A 295 4842 5665 4710 994 280 -41 c ATOM 1099 CD 1 LEU A 290 119.844 -24.496 -4.081 1.00 51.15 C ATOM 1144 C LEU A 295 122.107 -33.083 0.279 1.00 40.58 c ANISOU 1099 CD1 LEU A 290 8424 5681 5330 618 327 -1213 C ANISOU 1144 C LEU A 295 5955 5901 3562 1355 4 -414 c ATOM 1100 CD2 LEU A 290 118.237 -23.977 -5.920 1.00 56.81 C ATOM 1145 O LEU A 295 121.937 -33.857 1.223 1.00 68.34 o ANISOU 1100 CD2 LEU A 290 8966 6277 6340 836 669 -892 C ANISOU 1145 O LEU A 295 9595 9498 6874 1634 104 -216 o

ATOM 1101 C LEU A 290 120.863 -27.627 -5.448 1.0044.57 C ATOM 1146 N GLU A 296 123.226 -32.387 0.106 1.00 59.18 N

ANISOU 1101 C LEU A 290 6434 5514 4987 305 183 -922 C ANISOU 1146 N GLU A 296 8301 8313 5872 1129 -344 -693 N

ATOM 1102 O LEU A 290 120.674 -27.760 -4.240 1.00 55.20 O ATOM 1147 CA GLU A 296 124.305 -32.402 1.088 1.00 54.90 c

ANISOU 1102 O LEU A 290 7974 6888 6112 500 191 -946 O ANISOU 1147 CA GLU A 296 7888 7960 5013 1198 -694 -834 c

ATOM 1103 N PHE A 291 120.667 -28.606 -6.319 1.00 38.51 N ATOM 1148 CB GLU A 296 125.433 -31.460 0.676 1.00 62.30 c

ANISOU 1103 N PHE A 291 5308 4889 4435 287 234 -781 N ANISOU 1148 CB GLU A 296 8723 8922 6027 833 -1062 -1154 c ATOM 1104 CA PHE A 291 120.258 -29.941 -5.911 1.00 34.50 C ATOM 1149 CG GLU A 296 126.691 -32.166 0.242 1.00 83.26 c ANISOU 1104 CA PHE A 291 4592 4537 3981 445 299 -639 C ANISOU 1149 CG GLU A 296 10937 11809 8888 688 -1318 -1157 C

ATOM 1105 CB PHE A 291 119.939 -30.779 -7.155 1.00 38.37 C ATOM 1150 CD GLU A 296 127.875 -31.848 1.130 1.00103.45 C

ANISOU 1105 CB PHE A 291 4748 5092 4739 382 332 -541 C ANISOU 1150 CD GLU A 296 13523 14587 11195 645 -1790 -1381 C ATOM 1106 CG PHE A 291 119.667 -32.226 -6.858 1.00 30.11 C ATOM 1151 OE1 GLU A 296 127.991 -30.685 1.575 1.00112.17 O ANISOU 1106 CG PHE A 291 3492 4134 3814 471 374 -413 C ANISOU 1151 OE1 GLU A 296 14915 15588 12116 486 -1992 -1654 O ATOM 1107 CD1 PHE A 291 118.412 -32.640 -6.435 1.00 28.88 C ATOM 1152 OE2 GLU A 296 128.687 -32.765 1.388 1.00111.35 O ANISOU 1107 CD1 PHE A 291 3288 3953 3733 645 564 -234 C ANISOU 1152 OE2 GLU A 296 14268 15855 12184 782 -1982 -1292 O ATOM 1108 CE1 PHE A 291 118.156 -33.982 -6.164 1.00 29.10 C ATOM 1153 C GLU A 296 123.794 -31.990 2.463 1.00 53.69 C

ANISOU 1108 CE1 PHE A 291 3138 4000 3921 682 626 -89 C ANISOU 1153 C GLU A 296 8239 7803 4359 1523 -647 -854 C

ATOM 1109 CZ PHE A 291 119.174 -34.925 -6.313 1.00 32.34 C ATOM 1154 O GLU A 296 124.059 -32.657 3.462 1.00 60.30 O

ANISOU 1109 CZ PHE A 291 3461 4445 4384 599 485 -138 C ANISOU 1154 O GLU A 296 9218 8811 4882 1807 -725 -747 O ATOM 1110 CE2 PHE A 291 120.435 -34.513 -6.740 1.00 40.72 C ATOM 1155 N ASP A 297 123.064 -30.879 2.500 1.00 55.94 N ANISOU 1110 CE2 PHE A 291 4543 5578 5350 476 296 -322 C ANISOU 1155 N ASP A 297 8824 7888 4541 1524 -506 -985 N ATOM 1111 CD2 PHE A 291 120.671 -33.170 -7.011 1.00 35.92 C ATOM 1156 CA ASP A 297 122.544 -30.348 3.755 1.00 63.40 C ANISOU 1111 CD2 PHE A 291 4071 4962 4616 385 246 -450 C ANISOU 1156 CA ASP A 297 10308 8808 4972 1870 -428 -1046 C

ATOM 1112 C PHE A 291 121.351 -30.614 -5.066 1.00 46.79 C ATOM 1157 CB ASP A 297 121.808 -29.029 3.541 1.00 69.36 C

ANISOU 1112 C PHE A 291 6119 6231 5427 408 124 -703 C ANISOU 1157 CB ASP A 297 11365 9291 5699 1849 -273 -1221 C

ATOM 1113 O PHE A 291 121.070 -31.207 -4.025 1.0049.14 O ATOM 1158 CG ASP A 297 122.731 -27.903 3.151 1.00 99.54 C

ANISOU 1113 0 PHE A 291 6497 6589 5585 616 180 -612 O ANISOU 1158 CG ASP A 297 15271 12961 9589 1459 -667 -1613 C

ATOM 1114 N CYS A 292 122.599 -30.510 -5.518 1.00 41.14 N ATOM 1159 OD1 ASP A 297 123.961 -28.072 3.278 1.00110.44 O

ANISOU 1114 N CYS A 292 5274 5587 4770 168 -76 -832 N ANISOU 1159 OD1 ASP A 297 16501 14496 10965 1230 -1092 -1781 ATOM 1115 CA CYS A 292 123.730 -31.085 -4.794 1.00 46.08 C ATOM 1160 OD2 ASP A 297 122.215 -26.844 2.726 1.00109.93 O ANISOU 1115 CA CYS A 292 5812 6390 5309 146 -289 -896 C ANISOU 1160 OD2 ASP A 297 16794 13995 10981 1387 -542 -1734 ATOM 1116 CB CYS A 292 125.036 -30.921 -5.574 1.00 44.22 C ATOM 1161 C ASP A 297 121.599 -31.331 4.420 1.00 54.00 C ANISOU 1116 CB CYS A 292 5316 6261 5225 -138 -458 -1004 C ANISOU 1161 C ASP A 297 9182 7704 3633 2284 -17 -656 ATOM 1162 O ASP A 297 121.615 -31.505 5.630 1.00 66.19 O ATOM 1207 CG GLU A 304 117.079 -42.904 7.920 1.00 99.39 C ANISOU 1162 0 ASP A 297 11089 9371 4689 2632 -20 -612 o ANISOU 1207 CG GLU A 304 14390 12928 10447 3840 3265 3634 C ATOM 1163 N ILE A 298 120.766 -31.966 3.610 1.00 54.21 N ATOM 1208 CD GLU A 304 116.443 -41.521 8.013 1.00100.29 C ANISOU 1163 N FLE A 298 8857 7659 4082 2233 335 -366 N ANISOU 1208 CD GLU A 304 14523 13230 10352 3865 3332 3379 C ATOM 1164 CA ILE A 298 119.820 -32.929 4.131 1.00 51.45 C ATOM 1209 OE1 GLU A 304 115.216 -41.448 8.231 1.00 98.49 O ANISOU 1164 CA FLE A 298 8490 7349 3708 2541 761 43 c ANISOU 1209 OE1 GLU A 304 14123 12925 10373 3845 3744 3565 O ATOM 1165 CB FLE A 298 118.871 -33.421 3.046 1.00 51.13 c ATOM 1210 OE2 GLU A 304 117.168 -40.513 7.862 1.00100.65 O ANISOU 1165 CB FLE A 298 8013 7190 4222 2374 1073 279 c ANISOU 1210 OE2 GLU A 304 14738 13479 10027 3899 2941 2974 O ATOM 1166 CGI FLE A 298 117.975 -32.280 2.591 1.00 47.60 c ATOM 1211 C GLU A 304 120.911 -42.497 7.442 1.00 89.63 C ANISOU 1166 CGI FLE A 298 7620 6614 3852 2364 1250 176 c ANISOU 1211 C GLU A 304 13327 12146 8582 3960 1677 2705 C ATOM 1167 CD1 FLE A 298 117.042 -32.659 1.474 1.00 46.35 c ATOM 1212 0 GLU A 304 121.421 -43.504 6.962 1.00 78.68 O ANISOU 1167 CD1 FLE A 298 7010 6379 4220 2200 1475 368 c ANISOU 1212 0 GLU A 304 11775 10601 7521 3906 1584 2809 O ATOM 1168 CG2 FLE A 298 118.014 -34.568 3.568 1.00 60.58 c ATOM 1213 N SER A 305 121.446 -41.290 7.320 1.00 85.74 N ANISOU 1168 CG2 FLE A 298 9122 8408 5489 2603 1489 727 c ANISOU 1213 N SER A 305 12848 11888 7842 3869 1288 2236 N ATOM 1169 C FLE A 298 120.531 -34.113 4.767 1.00 52.33 c ATOM 1214 CA SER A 305 122.467 -41.022 6.322 1.00 87.73 C ANISOU 1169 C FLE A 298 8583 7623 3674 2685 641 227 c ANISOU 1214 CA SERA 305 12775 12204 8355 3568 805 1829 C ATOM 1170 O FLE A 298 120.211 -34.515 5.882 1.00 61.86 o ATOM 1215 CB SER A 305 122.027 -39.862 5.445 1.00 95.11 C ANISOU 1170 O FLE A 298 10088 8919 4497 3062 842 452 o ANISOU 1215 CB SER A 305 13514 13099 9523 3191 774 1478 C ATOM 1171 N LEU A 299 121.514 -34.654 4.060 1.00 57.38 N ATOM 1216 OG SERA 305 122.247 -38.645 6.132 1.00100.27 o ANISOU 1171 N LEU A 299 8895 8310 4598 2428 331 148 N ANISOU 1216 OG SER A 305 14466 13955 9676 3295 567 119 o ATOM 1172 CA LEU A 299 122.212 -35.848 4.521 1.00 51.71 c ATOM 1217 C SER A 305 123.813 -40.652 6.909 1.00 89.66 C ANISOU 1172 CA LEU A 299 8118 7725 3804 2591 217 345 c ANISOU 1217 C SER A 305 13155 12776 8136 3756 263 1572 C ATOM 1173 CB LEU A 299 123.093 -36.432 3.421 1.00 48.81 c ATOM 1218 O SER A 305 124.580 -39.915 6.287 1.00 81.56 O ANISOU 1173 CB LEU A 299 7306 7365 3874 2302 -24 270 c ANISOU 1218 0 SER A 305 11905 11877 7208 3487 -135 1166 O ATOM 1174 CG LEU A 299 122.363 -36.971 2.200 1.00 66.13 c ATOM 1219 N GLN A 306 124.098 -41.135 8.109 1.00 86.88 N ANISOU 1174 CG LEU A 299 9155 9351 6621 2078 249 409 c ANISOU 1219 N GLN A 306 13159 12575 7275 4212 239 1818 N ATOM 1175 CD1 LEU A 299 123.325 -37.735 1.310 1.00 63.97 c ATOM 1220 CA GLN A 306 125.373 -40.818 8.724 1.00 88.90 C ANISOU 1175 CD1 LEU A 299 8537 9103 6665 1918 33 355 c ANISOU 1220 CA GLN A 306 13520 13186 7071 4412 -339 1572 C ATOM 1176 CD2 LEU A 299 121.208 -37.862 2.634 1.00 58.44 c ATOM 1221 CB GLN A 306 125.223 -40.565 10.227 1.00106.68 c ANISOU 1176 CD2 LEU A 299 8242 8238 5726 2279 697 814 c ANISOU 1221 CB GLN A 306 16223 15550 8761 4738 -295 1591 c ATOM 1177 C LEU A 299 123.061 -35.587 5.755 1.00 63.98 c ATOM 1222 CG GLN A 306 125.659 -39.164 10.673 1.00122.35 c ANISOU 1177 C LEU A 299 10042 9504 4762 2858 -120 206 c ANISOU 1222 CG GLN A 306 18365 17726 10398 4623 -718 1078 c ATOM 1178 O LEU A 299 123.257 -36.475 6.579 1.00 70.06 o ATOM 1223 CD GLN A 306 124.735 -38.051 10.183 1.00136.76 c ANISOU 1178 0 LEU A 299 10956 10393 5271 3185 -91 463 o ANISOU 1223 CD GLN A 306 20271 19405 12288 4382 -504 881 c ATOM 1179 N ALA A 300 123.578 -34.370 5.867 1.00 64.53 N ATOM 1224 OE1 GLN A 306 123.668 -38.307 9.626 1.00142.59 o ANISOU 1179 N ALA A 300 10282 9618 4619 2713 -463 -202 N ANISOU 1224 OE1 GLN A 306 20950 19941 13286 4336 -3 1155 o ATOM 1180 CA ALA A 300 124.483 -34.035 6.956 1.00 72.54 c ATOM 1225 NE2 GLN A 306 125.147 -36.805 10.399 1.00138.57 N ANISOU 1180 CA ALA A 300 11622 10856 5084 2900 -904 -424 C ANISOU 1225 NE2 GLN A 306 20623 19709 12318 4209 -880 408 N ATOM 1181 CB ALA A 300 124.997 -32.619 6.814 1.00 62.85 C ATOM 1226 C GLN A 306 126.388 -41.914 8.424 1.00 88.57 C ANISOU 1181 CB ALA A 300 10519 9576 3784 2595 -1285 -918 C ANISOU 1226 C GLN A 306 13215 13198 7240 4532 -574 1705 C ATOM 1182 C ALA A 300 123.805 -34.222 8.309 1.00 83.96 C ATOM 1227 O GLN A 306 126.257 -43.052 8.881 1.00 87.25 O ANISOU 1182 C ALA A 300 13605 12371 5925 3426 -651 -214 c ANISOU 1227 O GLN A 306 13169 12886 7096 4800 -314 2092 O ATOM 1183 O ALA A 300 124.443 -34.604 9.290 1.00 88.19 o ATOM 1228 N ASN A 307 127.369 -41.551 7.602 1.00 87.94 N ANISOU 1183 O ALA A 300 14294 13079 6134 3660 -891 -188 o ANISOU 1228 N ASN A 307 12719 13263 7431 4245 -997 1343 N ATOM 1184 N ASP A 301 122.505 -33.961 8.354 1.00 76.83 N ATOM 1229 CA ASN A 307 128.536 -42.376 7.306 1.00 89.61 C ANISOU 1184 N ASP A 301 12878 11291 5025 3561 -124 -40 N ANISOU 1229 CA ASN A 307 12624 13619 7803 4387 -1301 1383 C ATOM 1185 CA ASP A 301 121.778 -34.046 9.609 1.00 75.30 c ATOM 1230 CB ASN A 307 129.231 -42.804 8.595 1.00102.12 C ANISOU 1185 CA ASP A 301 13036 11068 4508 3957 202 175 c ANISOU 1230 CB ASN A 307 14429 15409 8962 4755 -1504 1474 C ATOM 1186 CB ASP A 301 121.098 -32.708 9.929 1.00 95.50 c ATOM 1231 CG ASN A 307 130.720 -42.874 8.436 1.00113.55 C ANISOU 1186 CB ASP A 301 15894 13447 6944 3974 312 -78 c ANISOU 1231 CG ASN A 307 15478 17161 10504 4729 -2016 1246 C ATOM 1187 CG ASP A 301 121.805 -31.941 11.037 1.00120.84 c ATOM 1232 OD1 ASN A 307 131.289 -43.952 8.270 1.00119.30 O ANISOU 1187 CG ASP A 301 19495 16700 9719 4069 -107 -425 c ANISOU 1232 OD1 ASN A 307 16042 17858 11427 4934 -1993 1452 O ATOM 1188 OD1 ASP A 301 123.053 -31.965 11.087 1.00128.34 o ATOM 1233 ND2 ASN A 307 131.365 -41.715 8.445 1.00121.33 N ANISOU 1188 OD1 ASP A 301 20373 17799 10592 3887 -654 -674 o ANISOU 1233 ND2 ASN A 307 16288 18413 11400 4444 -2457 821 N ATOM 1189 OD2 ASP A 301 121.102 -31.317 11.863 1.00128.05 o ATOM 1234 C ASN A 307 128.343 -43.592 6.390 1.00 81.26 C ANISOU 1189 OD2 ASP A 301 20764 17506 10382 4330 109 -441 o ANISOU 1234 C ASN A 307 11345 12227 7305 4360 -973 1646 C ATOM 1190 C ASP A 301 120.739 -35.166 9.637 1.00 71.55 C ATOM 1235 O ASN A 307 129.138 -44.532 6.424 1.00 88.95 O ANISOU 1190 C ASP A 301 12425 10533 4226 4170 814 737 c ANISOU 1235 O ASN A 307 12218 13259 8319 4660 -1110 1813 O ATOM 1191 O ASP A 301 119.971 -35.278 10.582 1.00 87.78 o ATOM 1236 N ASN A 308 127.311 -43.577 5.560 1.00 73.11 N ANISOU 1191 O ASP A 301 14694 12542 6118 4477 1169 965 o ANISOU 1236 N ASN A 308 10240 10840 6700 4021 -572 1665 N ATOM 1192 N ALA A 302 120.706 -35.997 8.604 1.00 73.18 N ATOM 1237 CA ASN A 308 127.097 -44.695 4.650 1.00 75.76 C ANISOU 1192 N ALA A 302 12245 10710 4852 3973 934 962 N ANISOU 1237 CA ASN A 308 10402 10820 7564 3954 -309 1846 C ATOM 1193 CA ALA A 302 119.666 -37.019 8.538 1.00 71.92 c ATOM 1238 CB ASN A 308 126.024 -45.626 5.200 1.00 79.22 C ANISOU 1193 CA ALA A 302 11904 10420 5002 4064 1516 1488 C ANISOU 1238 CB ASN A 308 11169 10892 8039 4134 179 2322 C ATOM 1194 CB ALA A 302 119.262 -37.292 7.104 1.00 60.51 C ATOM 1239 CG ASN A 308 124.826 -44.874 5.730 1.00 83.81 C ANISOU 1194 CB ALA A 302 9898 8763 4328 3608 1608 1501 C ANISOU 1239 CG ASN A 308 11968 11438 8438 4020 484 2392 C ATOM 1195 C ALA A 302 120.060 -38.313 9.241 1.00 86.36 C ATOM 1240 OD1 ASN A 308 124.714 -43.664 5.548 1.00 61.56 O ANISOU 1195 C ALA A 302 13798 12291 6725 4315 1561 1854 C ANISOU 1240 OD1 ASN A 308 9072 8802 5516 3786 342 2056 o ATOM 1196 O ALA A 302 121.096 -38.901 8.929 1.00 87.89 O ATOM 1241 ND2 ASN A 308 123.926 -45.585 6.398 1.00 95.78 N ANISOU 1196 0 ALA A 302 13858 12552 6983 4247 1190 1810 O ANISOU 1241 ND2 ASN A 308 13761 12708 9923 4203 934 2852 N ATOM 1197 N PRO A 303 119.223 -38.754 10.199 1.00 90.87 N ATOM 1242 C ASN A 308 126.707 -44.223 3.267 1.00 65.05 C ANISOU 1197 N PRO A 303 14508 12782 7237 4584 2004 2185 N ANISOU 1242 C ASN A 308 8722 9300 6693 3459 -229 1559 C ATOM 1198 CA PRO A 303 119.346 -39.984 10.993 1.00 95.18 C ATOM 1243 O ASN A 308 126.101 -44.954 2.488 1.00 63.44 o ANISOU 1198 CA PRO A 303 15137 13299 7728 4838 2173 2566 C ANISOU 1243 0 ASN A 308 8447 8738 6921 3315 48 1666 o ATOM 1199 CB PRO A 303 117.906 -40.241 11.447 1.00 83.53 C ATOM 1244 N CYS A 309 127.064 -42.984 2.973 1.00 55.06 N ANISOU 1199 CB PRO A 303 13619 11663 6456 4945 2822 2941 C ANISOU 1244 N CYS A 309 7290 8288 5342 3199 -491 1188 N ATOM 1200 CG PRO A 303 117.231 -38.892 11.421 1.00 80.65 C ATOM 1245 CA CYS A 309 126.673 -42.362 1.736 1.00 50.64 C ANISOU 1200 CG PRO A 303 13319 11330 5996 4931 2879 2672 C ANISOU 1245 CA CYS A 309 6479 7608 5152 2763 -417 933 c ATOM 1201 CD PRO A 303 118.129 -37.910 10.704 1.00 87.77 C ATOM 1246 CB CYS A 309 125.306 -41.706 1.899 1.00 55.78 c ANISOU 1201 CD PRO A 303 14250 12335 6763 4709 2340 2163 C ANISOU 1246 CB CYS A 309 7323 8091 5781 2596 -118 975 c ATOM 1202 C PRO A 303 119.839 -41.197 10.208 1.00 90.58 C ATOM 1247 SG CYS A 309 124.592 -41.092 0.370 1.00109.82 s ANISOU 1202 C PRO A 303 14281 12599 7537 4674 2120 2807 C ANISOU 1247 SG CYS A 309 13897 14750 13079 2128 10 742 s ATOM 1203 O PRO A 303 120.660 -41.961 10.711 1.00 87.61 O ATOM 1248 C CYS A 309 127.720 -41.323 1.391 1.00 62.38 c ANISOU 1203 O PRO A 303 14015 12278 6994 4871 1921 2899 O ANISOU 1248 C CYS A 309 7714 9419 6568 2568 -806 567 c ATOM 1204 N GLU A 304 119.335 -41.373 8.993 1.00 85.28 N ATOM 1249 O CYS A 309 128.319 -40.719 2.275 1.00 61.60 o ANISOU 1204 N GLU A 304 13260 11744 7398 4332 2289 2905 N ANISOU 1249 0 CYS A 309 7710 9600 6094 2674 -1105 463 o ATOM 1205 CA GLU A 304 119.609 -42.584 8.231 1.00 95.23 C ATOM 1250 N ARG A 310 127.946 -41.117 0.104 1.00 59.92 N ANISOU 1205 CA GLU A 304 14249 12770 9164 4150 2287 3131 C ANISOU 1250 N ARG A 310 7089 9066 6614 2275 -807 372 N ATOM 1206 CB GLU A 304 118.454 -42.883 7.269 1.00 93.31 C ATOM 1251 CA ARG A 310 128.938 -40.150 -0.317 1.00 53.28 c ANISOU 1206 CB GLU A 304 13592 12223 9639 3745 2661 3267 C ANISOU 1251 CA ARG A 310 5967 8503 5776 2043 -1113 72 c





 ANISOU 1542 CG LEUB 159 6523 5642 5404 -537 764 293 C ANISOU 1587 CDl TYRB 164 4663 6212 4724 -684 -458 -619 C ATOM 1543 CD2LEUB 159 106.741 -32.721 -4.652 1.0045.94 C ATOM 1588 CE1 TYRB 164 104.921 -38.952-19.000 1.0052.04 C ANISOU 1543 CD2 LEUB 159 6701 5371 5384 -774 1116 73 C ANISOU 1588 CE1 TYRB 164 6235 7769 5767 -1035 -582 -704 C ATOM 1544 CDl LEUB 159 108.940 -33.159 -5.699 1.0054.73 C ATOM 1589 CZ TYRB 164 105.891 -38.321 -19.762 1.0057.32 C ANISOU 1544 CDl LEUB 159 7794 6840 6162 -595 483 677 C ANISOU 1589 CZ TYRB 164 7106 8610 6063 -1183 -657 -610 C ATOM 1545 C LEUB 159 106.771 -33.993 -9.415 1.0034.06 C ATOM 1590 OH TYRB 164 105.974-38.562-21.110 1.0066.85 O ANISOU 1545 c 159 4156 4484 4300 59 222 167 C ANISOU 1590 OH TYRB 164 8569 9985 6847 -1631 -735 -721 O ATOM 1546 O LEU I i 159 106.878 -35.206 -9.605 1.0033.81 O ATOM 1591 CE2TYRB 164 106.785 -37.443-19.178 1.0053.77 C ANISOU 1546 o 159 4095 4495 4256 47 294 124 O ANISOU 1591 CE2TYRB 164 6639 8165 5627 -943 -642 -411 C ATOM 1547 N ALA I i 160 105.922-33.227 -10.089 1.0029.30 N ATOM 1592 CD2TYRB 164 106.708 -37.200-17.831 1.0049.78 C ANISOU 1547 N ALA B 160 3333 3857 3943 145 75 81 N ANISOU 1592 CD2TYRB 164 5960 7492 5463 -599 -553 -313 C ATOM 1548 CA ALA B 160 105.052 -33.767-11.118 1.0033.09 C ATOM 1593 C TYRB 164 107.324-39.409 -15.280 1.0040.21 C ANISOU 1548 CA ALAB 160 3545 4392 4634 184 -60 -42 C ANISOU 1593 C TYRB 164 4641 5838 4801 -184 297 -483 C ATOM 1549 CB ALAB 160 104.076 -32.714-11.606 1.0028.13 C ATOM 1594 O TYRB 164 107.243 -40.521 -15.804 1.0037.31 O ANISOU 1549 CB ALAB 160 2647 3652 4388 242 -281 -49 C ANISOU 1594 O TYRB 164 4291 5434 4452 -291 499 -697 O ATOM 1550 C ALAB 160 105.875 -34.325 -12.283 1.0038.04 C ATOM 1595 N ILEB 165 108.462 -38.752-15.180 1.0030.92 N ANISOU 1550 C ALAB 160 4223 5270 4960 161 -263 57 C ANISOU 1595 N ILEB 165 3529 4712 3507 -113 275 -281 N ATOM 1551 O ALAB 160 105.629-35.430 -12.770 1.0031.69 O ATOM 1596 CA ILEB 165 109.696-39.275 -15.703 1.0031.32 C ANISOU 1551 O ALAB 160 3368 4518 4154 111 -199 -73 O ANISOU 1596 CA ILEB 165 3629 4780 3490 -151 497 -299 C ATOM 1552 N TRPB 161 106.852 -33.551 -12.731 1.0030.18 N ATOM 1597 CB ILEB 165 110.793 -38.200-15.709 1.0033.02 C ANISOU 1552 N TRPB 161 3343 4413 3712 168 -463 261 N ANISOU 1597 CB ILEB 165 3889 5094 3562 -96 368 -34 C ATOM 1553 CA TRPB 161 107.751 -34.033 -13.763 1.0036.31 C ATOM 1598 CGI ILEB 165 110.470 -37.098 -16.706 1.0035.79 C ANISOU 1553 CA TRPB 161 4195 5402 4199 102 -544 316 C ANISOU 1598 CGI ILEB 165 4333 5673 3593 -242 45 -3 C ATOM 1554 CB TRPB 161 108.682 -32.927 -14.240 1.0034.27 C ATOM 1599 CDl ILEB 165 110.094-37.550 -18.016 1.0030.89 C ANISOU 1554 CB TRPB 161 4043 5282 3696 87 -778 544 C ANISOU 1599 CDl ILEB 165 3822 5188 2728 -534 92 -246 C ATOM 1555 CG TRPB 161 107.969 -32.038 -15.169 1.0024.91 C ATOM 1600 CG2 ILEB 165 112.142 -38.783 -15.962 1.0026.33 C ANISOU 1555 CG TRPB 161 2762 4152 2551 15 -1150 599 C ANISOU 1600 CG2 ILEB 165 3006 4189 2810 -97 672 -29 C ATOM 1556 CDl TRPB 161 107.358-30.854-14.875 1.0029.59 C ATOM 1601 C ILEB 165 110.202-40.535 -15.024 1.0039.00 C ANISOU 1556 CDl TRPB 161 3250 4604 3391 82 -1357 700 C ANISOU 1601 C ILEB 165 4520 5510 4789 -56 826 -330 C ATOM 1557 NE1 TRPB 161 106.771 -30.339 -16.000 1.0032.70 N ATOM 1602 O ILEB 165 110.686 -41.435-15.667 1.0047.32 O ANISOU 1557 NE1 TRPB 161 3575 5001 3848 -12 -1640 717 N ANISOU 1602 O ILEB 165 5550 6484 5945 -118 1123 -510 O ATOM 1558 CE2 TRPB 161 106.977 -31.208 -17.047 1.0033.34 C ATOM 1603 N GLYB 166 110.100-40.567 -13.712 1.0040.03 N ANISOU 1558 CE2TRPB 161 3753 5261 3652 -195 -1662 641 C ANISOU 1603 N GLYB 166 4619 5493 5098 54 783 -152 N ATOM 1559 CD2TRPB 161 107.720-32.293 -16.546 1.0040.53 C ATOM 1604 CA GLYB 166 110.625 -41.640-12.925 1.0036.59 C ANISOU 1559 CD2 TRPB 161 4737 6301 4363 -188 -1381 572 C ANISOU 1604 CA GLYB 166 4110 4803 4991 108 982 -58 C ATOM 1560 CE3 TRPB 161 108.073 -33.331 -17.420 1.0026.85 C ATOM 1605 C GLYB 166 109.706 -42.758 -12.547 1.0040.38 C ANISOU 1560 CE3TRPB 161 3113 4721 2366 -374 -1249 424 C ANISOU 1605 C GLYB 166 4563 5121 5657 70 1120 -238 C ATOM 1561 CZ3 TRPB 161 107.675 -33.251 -18.742 1.0037.79 C ATOM 1606 O GLYB 166 110.115-43.643 -11.873 1.0043.27 O ANISOU 1561 CZ3TRPB 161 4569 6222 3567 -656 -1518 416 C ANISOU 1606 O GLYB 166 4876 5247 6316 88 1229 -114 O ATOM 1562 CH2TRPB 161 106.932-32.154-19.213 1.0041.76 C ATOM 1607 N TYRB 167 108.455 -42.676 -12.935 1.0031.17 N ANISOU 1562 CH2 TRPB 161 5014 6560 4292 -635 -1803 533 C ANISOU 1607 N TYRB 167 3417 4065 4361 -4 1079 -491 N ATOM 1563 CZ2 TRPB 161 106.576 -31.122-18.382 1.0037.46 C ATOM 1608 CA TYRB 167 107.505-43.715 -12.650 1.0039.43 C ANISOU 1563 CZ2TRPB 161 4319 5834 4082 -396 -1863 637 C ANISOU 1608 CA TYRB 167 4429 4969 5583 -60 1221 -681 C ATOM 1564 C TRPB 161 108.548 -35.254-13.328 1.0034.70 C ATOM 1609 CB TYRB 167 106.820 -43.484-11.323 1.0028.55 C ANISOU 1564 C TRPB 161 4073 5172 3940 107 -245 280 C ANISOU 1609 CB TYRB 167 3086 3508 4253 -71 1158 -563 C ATOM 1565 O TRPB161 108.729 -36.192-14.098 1.0032.00 O ATOM 1610 CG TYRB 167 105.890-44.568 -10.958 1.0034.39 C ANISOU 1565 O TRPB 161 3712 4896 3550 44 -146 156 O ANISOU 1610 CG TYRB 167 3796 4100 5172 -153 1315 -741 C ATOM 1566 N ALAB 162 109.029-35.241 -12.093 1.0028.82 N ATOM 1611 CDl TYRB 167 106.352 -45.820-10.638 1.0041.93 C ANISOU 1566 N ALAB 162 3426 4299 3224 141 -109 403 N ANISOU 1611 CDl TYRB 167 4740 4829 6362 -171 1485 -710 C ATOM 1567 CA ALAB 162 109.778 -36.380-11.572 1.0029.10 C ATOM 1612 CE1 TYRB 167 105.513 -46.806-10.317 1.0030.94 C ANISOU 1567 CA ALAB 162 3499 4249 3309 128 94 458 C ANISOU 1612 CE1 TYRB 167 3336 3295 5124 -267 1619 -864 C ATOM 1568 CB ALAB 162 110.371 -36.060 -10.219 1.0027.34 C ATOM 1613 CZ TYRB 167 104.189 -46.571 -10.310 1.0040.47 C ANISOU 1568 CB ALAB 162 3440 3905 3045 69 102 702 C ANISOU 1613 CZ TYRB 167 4518 4595 6263 -346 1604 -1061 C ATOM 1569 C ALAB 162 108.896 -37.634-11.483 1.0031.94 C ATOM 1614 OH TYRB 167 103.337 -47.567 -9.970 1.0050.37 O ANISOU 1569 C ALAB 162 3772 4499 3865 105 294 220 C ANISOU 1614 OH TYRB 167 5752 5717 7670 -460 1746 -1216 O ATOM 1570 O ALAB 162 109.353-38.754-11.702 1.0046.58 O ATOM 1615 CE2TYRB 167 103.699 -45.345-10.614 1.0036.07 C ANISOU 1570 O ALA B 162 5582 6299 5818 103 447 182 O ANISOU 1615 CE2TYRB 167 3918 4230 5555 -313 1445 -1087 C ATOM 1571 N TYRI i 163 107.632 -37.438 -11.138 1.0033.94 N ATOM 1616 CD2TYRB 167 104.542 -44.358-10.939 1.0039.25 C ANISOU 1571 N TYRI 163 3977 4685 4233 85 316 57 N ANISOU 1616 CD2TYRB 167 4356 4764 5791 -218 1291 -923 C ATOM 1572 CA TYRI B 163 106.722-38.560 -10.979 1.0036.48 C ATOM 1617 C TYRB 167 106.501 -44.020 -13.752 1.0039.73 C ANISOU 1572 CA TYR ! 163 4215 4901 4743 42 499 -163 C ANISOU 1617 C TYRB 167 4455 5126 5516 -192 1212 -995 C ATOM 1573 CB TYRB 163 105.448 -38.111 -10.268 1.0027.18 C ATOM 1618 O TYRB 167 106.489 -45.079 -14.286 1.0049.78 O ANISOU 1573 CB TYRB 163 2977 3601 3750 9 577 -303 C ANISOU 1618 O TYRB 167 5733 6312 6869 -281 1422 -1216 O ATOM 1574 CG TYRB 163 104.498-39.234 -9.938 1.0035.21 C ATOM 1619 N LEUB 168 105.650 -43.069 -14.059 1.0038.42 N ANISOU 1574 CG TYRB 163 3914 4498 4967 -61 790 -517 C ANISOU 1619 N LEUB 168 4266 5126 5205 -231 951 -994 N ATOM 1575 CDl TYRB 163 104.943 -40.378 -9.274 1.0044.03 C ATOM 1620 CA LEUB 168 104.580 -43.235 -14.996 1.0043.70 C ANISOU 1575 CDl TYRB 163 5156 5515 6059 -140 967 -479 C ANISOU 1620 CA LEUB 168 4899 5896 5809 -408 819 -1197 C ATOM 1576 CE1 TYRB 163 104.073 -41.407 -8.967 1.0035.72 C ATOM 1621 CB LEUB 168 103.733 -41.984-15.022 1.0035.81 C ANISOU 1576 CE1 TYRB 163 4046 4349 5178 -225 1155 -666 C ANISOU 1621 CB LEUB 168 3785 5003 4818 -408 467 -1082 C ATOM 1577 CZ TYRB 163 102.739 -41.290 -9.323 1.0036.72 C ATOM 1622 CG LEUB 168 102.958 -41.719 -13.757 1.0049.06 C ANISOU 1577 CZ TYRB 163 3964 4468 5522 -226 1179 -900 C ANISOU 1622 CG LEUB 168 5326 6527 6789 -282 526 -1041 C ATOM 1578 OH TYRB 163 101.861 -42.295 -9.025 1.0044.92 O ATOM 1623 CDl LEU I ! 168 102.083 -40.540 -13.960 1.0052.56 C ANISOU 1578 OH TYRB 163 4932 5397 6738 -324 1368 -1085 O ANISOU 1623 CDl LEU 168 5572 6998 7399 -283 223 -971 C ATOM 1579 CE2TYRB 163 102.278 -40.159 -9.981 1.0041.54 C ATOM 1624 CD2LEUI ! 168 102.148 -42.900 -13.390 1.0047.62 C ANISOU 1579 CE2TYRB 163 4403 5154 6225 -144 980 -913 C ANISOU 1624 CD2 LEU 168 5087 6197 6809 -343 756 -1233 C ATOM 1580 CD2TYRB 163 103.154-39.144-10.283 1.0032.94 C ATOM 1625 C LEU I ! 168 104.998 -43.560 -16.408 1.0046.97 C ANISOU 1580 CD2TYRB 163 3398 4172 4946 -64 782 -720 C ANISOU 1625 C LEU 168 5452 6424 5969 -620 869 -1363 C ATOM 1581 C TYRB 163 106.416 -39.157 -12.352 1.0042.75 C ATOM 1626 O LEU] i 168 104.392 -44.352 -17.051 1.0042.91 O ANISOU 1581 C TYRB 163 4894 5812 5537 22 445 -339 C ANISOU 1626 O LEU 168 4986 5889 5430 -823 955 -1599 O ATOM 1582 O TYRB 163 106.279 -40.373 -12.519 1.0036.33 O ATOM 1627 N ARG 3169 106.029 -42.934-16.907 1.0044.92 N ANISOU 1582 O TYRB 163 4055 4934 4813 -21 617 -486 O ANISOU 1627 N ARGI B 169 5291 6281 5495 -627 845 -1264 N ATOM 1583 N TYRB 164 106.339 -38.282 -13.344 1.0039.30 N ATOM 1628 CA ARGI ! 169 106.448 -43.261 -18.265 1.0051.77 C ANISOU 1583 N TYRB 164 4423 5535 4973 3 192 -311 N ANISOU 1628 CA ARG 169 6345 7255 6068 -915 963 -1469 C ATOM 1584 CA TYRB 164 106.093-38.716 -14.702 1.0038.13 C ATOM 1629 CB ARG B 169 107.262 -42.140-18.904 1.0047.70 C ANISOU 1584 CA TYRB 164 4256 5521 4711 -136 96 -451 C ANISOU 1629 CB ARGB 169 5942 6938 5244 -989 804 -1317 C ATOM 1585 CB TYRB 164 105.678 -37.534-15.568 1.0037.79 C ATOM 1630 CG ARGB 169 108.733 -42.167 -18.591 1.0048.59 C ANISOU 1585 CB TYRB 164 4173 5618 4566 -221 -297 -347 C ANISOU 1630 CG ARGB 169 6032 6960 5470 -810 1118 -1243 C ATOM 1586 CG TYRB 164 105.746-37.817 -17.043 1.0045.68 C ATOM 1631 CD ARGB 169 109.431 -41.113 -19.415 1.0054.09 C ANISOU 1586 CG TYRB 164 5275 6799 5280 -485 -443 -426 C ANISOU 1631 CD ARGB 169 6869 7877 5806 -964 976 -1141 C ATOM 1587 CDl TYRB 164 104.855 -38.696-17.646 1.0041.06 C ATOM 1632 NE ARGB 169 110.850 -41.013-19.107 1.0063.98 N

 ANISOU 1722 CG ARG l i 180 13166 12380 12201 -4212 1280 -3807 C ANISOU 1767 C HIS 185 12734 10354 15229 -2939 3793 -4232 C ATOM 1723 CD ARG B 180 94.511 -56.305 -23.887 1.00116.30 C ATOM 1768 O HIS ] i 185 94.040 -67.867 -15.533 1.00 95.59 O ANISOU 1723 CD ARG l i 180 15704 14718 13768 -4718 1066 -3777 C ANISOU 1768 O HIS I 185 12077 9458 14787 -2956 3934 -4255 O ATOM 1724 NE ARG B 180 93.754 -55.121 -24.266 1.00123.66 N ATOM 1769 CA HIS I B 185 94.997 -66.425 -17.194 1.00 99.08 C ANISOU 1724 NE ARG l ! 180 16497 15864 14624 -4896 332 -3426 N ANISOU 1769 CA HIS 185 12681 10195 14771 -3067 3965 -4409 C ATOM 1725 CZ ARG B 180 93.266 -54.910 -25.482 1.00130.00 C ATOM 1770 CB HIS I ! 185 96.499 -66.349 -16.931 1.00110.66 C ANISOU 1725 CZ ARG l 180 17556 16830 15009 -5382 -88 -3258 C ANISOU 1770 CB HIS 185 14033 11454 16557 -2791 4224 -4305 C ATOM 1726 NH1 ARG l ! 180 93.452 -55.812 -26.437 1.00119.89 N ATOM 1771 CG HIS I i 185 97.322 -66.215 -18.165 1.00130.05 C ANISOU 1726 NH1 ARG 180 16728 15547 13276 -5784 212 -3459 N ANISOU 1771 CG HIS B 185 16644 13929 18838 -2945 4489 -4497 C ATOM 1727 NH2 ARG l ! 180 92.586 -53.802 -25.743 1.00138.81 N ATOM 1772 NDl HIS B 185 96.759 -66.074 -19.429 1.00137.01 N ANISOU 1727 NH2 ARG 180 18456 18085 16200 -5470 -790 -2866 N ANISOU 1772 NDl HIS B 185 17811 15031 19214 -3339 4466 -4733 N ATOM 1728 C ARG B 180 95.532 -59.554 -20.316 1.00 77.93 C ATOM 1773 CE1 HIS I i 185 97.709 -65.978 -20.324 1.00140.50 C ANISOU 1728 C ARG B 180 10281 8932 10398 -3496 2620 -4195 C ANISOU 1773 CE1 HIS : 185 18375 15439 19570 -3455 4773 -4870 C ATOM 1729 O ARG B 180 94.776 -60.517 -20.407 1.00 73.54 O ATOM 1774 NE2 HIS I i 185 98.884 -66.053 -19.708 1.00138.79 N ANISOU 1729 O ARG B 180 9780 8296 9866 -3672 2647 -4286 O ANISOU 1774 NE2 HB B 185 17918 14972 19845 -3127 4992 -4734 N ATOM 1730 N THR B 181 96.817 -59.669 -20.011 1.00 76.75 N ATOM 1775 CD2 HIS I i 185 98.657 -66.202 -18.365 1.00132.42 C ANISOU 1730 N THR B 181 10101 8620 10439 -3221 3005 -4200 N ANISOU 1775 CD2 HIS B 185 16870 14050 19395 -2814 4788 -4485 C ATOM 1731 CA THR B 181 97.389 -60.967 -19.704 1.00 84.43 C ATOM 1776 N TYR B 186 93.765 -65.658 -15.242 1.00 92.09 N ANISOU 1731 CA THR B 181 11052 9284 11742 -3102 3455 -4281 C ANISOU 1776 N TYR B 186 13438 8920 12630 -3015 1796 -991 N ATOM 1732 CB THR B 181 98.907 -60.897 -19.502 1.00 85.82 C ATOM 1777 CA TYR B 186 93.012 -65.832 -14.008 1.00 88.87 C ANISOU 1732 CB THR B 181 11138 9278 12194 -2839 3780 -4210 C ANISOU 1777 CA TYR B 186 12741 8837 12189 -3077 1542 -708 C ATOM 1733 OG1 THR B 181 99.547 -60.747 -20.775 1.00 89.45 O ATOM 1778 CB TYR B 186 93.629 -65.012 -12.880 1.00 90.65 C ANISOU 1733 OG1 THR B 181 11837 9810 12342 -3115 3992 -4384 O ANISOU 1778 CB TYR B 186 12572 9210 12659 -2626 1504 -557 C ATOM 1734 CG2 THR B 181 99.414 -62.170 -18.838 1.00 69.58 C ATOM 1779 CG TYR B 186 94.946 -65.571 -12.407 1.00 99.96 C ANISOU 1734 CG2 THR B 181 8933 6848 10657 -2657 4116 -4188 C ANISOU 1779 CG TYR B 186 13836 9864 14281 -2356 1687 -556 C ATOM 1735 C THR B 181 96.728 -61.548 -18.464 1.00 78.25 C ATOM 1780 CD2 TYR B 186 94.995 -66.482 -11.360 1.00 99.50 C ANISOU 1735 C THR B 181 10046 8352 11333 -2892 3393 -4166 C ANISOU 1780 CD2 TYR B 186 13732 9656 14416 -2417 1598 -333 C ATOM 1736 O THR B 181 96.349 -62.718 -18.434 1.00 91.21 O ATOM 1781 CE2 TYR B 186 96.192 -67.005 -10.930 1.00107.20 C ANISOU 1736 O THR B 181 11729 9828 13096 -2988 3560 -4268 O ANISOU 1781 CE2 TYR B 186 14749 10161 15820 -2157 1746 -278 C ATOM 1737 N TYR B 182 96.574 -60.715 -17.444 1.00 65.42 N ATOM 1782 CZ TYR B 186 97.365 -66.623 -11.551 1.00111.75 C ANISOU 1737 N TYR B 182 8204 6785 9868 -2640 3165 -3957 N ANISOU 1782 CZ TYR B 186 15405 10422 16632 -1831 2005 -475 C ATOM 1738 CA TYR B 182 95.981 -61.170 -16.195 1.00 65.09 C ATOM 1783 OH TYR B 186 98.561 -67.147 -11.119 1.00118.66 O ANISOU 1738 CA TYR B 182 7978 6614 10140 -2485 3132 -3828 C ANISOU 1783 OH TYR B 186 16276 10854 17956 -1555 2152 -395 O ATOM 1739 CB TYR B 182 96.085 -60.090 -15.123 1.00 62.91 C ATOM 1784 CE1 TYR B 186 97.345 -65.724 -12.599 1.00106.05 C ANISOU 1739 CB TYR B 182 7510 6397 9994 -2237 2962 -3601 C ANISOU 1784 CE1 TYR B 186 14751 9844 15700 -1790 2110 -729 C ATOM 1740 CG TYR B 182 95.529 -60.536 -13.799 1.00 70.58 C ATOM 1785 CD1 TYR B 186 96.139 -65.206 -13.023 1.00104.61 C ANISOU 1740 CG TYR B 182 8348 7241 11227 -2143 2973 -3461 C ANISOU 1785 CD1 TYR B 186 14536 10118 15094 -2053 1943 -754 C ATOM 1741 CD1 TYR B 182 96.340 -61.170 -12.865 1.00 74.18 C ATOM 1786 C TYR B 186 91.546 -65.481 -14.205 1.00 85.90 C ANISOU 1741 CD1 TYR B 182 8794 7438 11954 -1969 3144 -3287 C ANISOU 1786 C TYR B 186 12209 9058 11371 -3404 1290 -604 C ATOM 1742 CE1 TYR B 182 95.834 -61.582 -11.659 1.00 70.79 C ATOM 1787 O TYR B 186 90.873 -65.002 -13.295 1.00 82.87 O ANISOU 1742 CE1 TYR B 182 8317 6901 11681 -1955 3134 -3147 C ANISOU 1787 O TYR B 186 11448 9134 10905 -3350 1081 -398 O ATOM 1743 CZ TYR B 182 94.494 -61.366 -11.384 1.00 73.73 C ATOM 1788 N ASN B 187 91.063 -65.736 -15.413 1.00 88.63 N ANISOU 1743 CZ TYR B 182 8611 7431 11971 -2090 3020 -3207 C ANISOU 1788 N ASN I i 187 12838 9410 11428 -3763 1322 -753 N ATOM 1744 OH TYR B 182 93.947 -61.771 -10.196 1.00 75.59 O ATOM 1789 CA ASN ] i 187 89.694 -65.419 -15.784 1.00 94.92 C ANISOU 1744 OH TYR B 182 8831 7581 12307 -2121 3050 -3086 O ANISOU 1789 CA ASN B 187 13489 10789 11788 -4101 1083 -642 C ATOM 1745 CE2 TYR B 182 93.676 -60.746 -12.296 1.00 67.69 C ATOM 1790 CB ASN ] i 187 89.539 -65.529 -17.296 1.00103.73 C ANISOU 1745 CE2 TYR B 182 7780 6896 11043 -2223 2857 -3371 C ANISOU 1790 CB ASN 187 14945 11853 12616 -4443 1175 -841 C ATOM 1746 CD2 TYR B 182 94.190 -60.337 -13.490 1.00 64.00 C ATOM 1791 CG ASN ] i 187 88.137 -65.231 -17.754 1.00107.80 C ANISOU 1746 CD2 TYR B 182 7398 6531 10389 -2265 2798 -3483 C ANISOU 1791 CG ASN ] B 187 15296 12999 12666 -4821 912 -688 C ATOM 1747 C TYR B 182 94.521 -61.577 -16.391 1.00 70.13 ATOM 1792 OD1 ASN ] B 187 87.414 -64.459 -17.124 1.00108.18 O ANISOU 1747 C TYR B 182 8623 7343 10678 -2744 2943 -3929 ANISOU 1792 OD1 ASN 187 14898 13560 12646 -4661 690 -457 O ATOM 1748 O TYR B 182 94.052 -62.560 -15.816 1.00 74.03 O ATOM 1793 ND2 ASN ] i 187 87.736 -65.849 -18.859 1.00113.17 N ANISOU 1748 O TYR B 182 9080 7682 11367 -2746 3046 -3931 O ANISOU 1793 ND2 ASN 187 16323 13657 13019 -5343 946 -817 N ATOM 1749 N ASN B 183 93.808 -60.813 -17.211 1.00 66.39 N ATOM 1794 C ASN ] i 187 88.662 -66.307 -15.088 1.00 93.03 C ANISOU 1749 N ASN I i 183 8187 7114 9923 -2987 2620 -3976 N ANISOU 1794 C ASN 187 13200 10767 11379 -4490 881 -463 C ATOM 1750 CA ASN I i 183 92.408 -61.092 -17.485 1.00 66.46 ATOM 1795 O ASN ] i 187 87.596 -65.841 -14.682 1.00 92.57 O ANISOU 1750 CA ASN B 183 8157 7210 9885 -3269 2347 -4006 ANISOU 1795 O ASN B 187 12790 11296 11085 -4582 640 -270 O ATOM 1751 CB ASN I i 183 91.748 -59.914 -18.191 1.00 75.57 ATOM 1796 N ASN ] i 188 88.977 -67.591 -14.969 1.00 80.71 N ANISOU 1751 CB ASN 183 9235 8623 10856 -3488 1859 -3907 ANISOU 1796 N ASN I B 188 11994 8723 9951 -4721 993 -528 N ATOM 1752 CG ASN ] i 183 91.284 -58.850 -17.227 1.00 70.44 ATOM 1797 CA ASN ] B 188 88.124 -68.517 -14.243 1.00 93.86 C ANISOU 1752 CG ASN ] B 183 8196 8035 10532 -3258 1658 -3709 ANISOU 1797 CA ASN 188 13655 10520 11487 -5099 817 -352 C ATOM 1753 OD1 ASN ] B 183 91.136 -59.101 -16.030 1.00 69.33 O ATOM 1798 CB ASN ] ! 188 88.709 -69.924 -14.299 1.00102.50 C ANISOU 1753 OD1 ASN 183 7878 7765 10698 -3018 1864 -3665 O ANISOU 1798 CB ASN 188 15226 10914 12803 -5303 1009 -460 C ATOM 1754 ND2 ASN ] i 183 91.045 -57.648 -17.744 1.00 73.30 N ATOM 1799 CG ASN ] i 188 88.572 -70.548 -15.656 1.00105.14 C ANISOU 1754 ND2 ASN 183 8430 8589 10833 -3354 1257 -3567 N ANISOU 1799 CG ASN ] 188 16043 10993 12913 -5740 1181 -729 C ATOM 1755 C ASN i 183 92.226 -62.346 -18.318 1.00 77.56 C ATOM 1800 OD1 ASN ] 188 87.574 -70.341 -16.341 1.00116.01 O ANISOU 1755 C ASN B 183 9833 8526 11109 -3559 2504 -4199 C ANISOU 1800 OD1 ASN 188 17406 12836 13835 -6133 1043 -736 O ATOM 1756 O ASN B 183 91.109 -62.822 -18.523 1.00 75.62 O ATOM 1801 ND2 ASN ] i 188 89.580 -71.311 -16.066 1.00 95.53 N ANISOU 1756 O ASN B 183 9582 8309 10840 -3810 2306 -4220 O ANISOU 1801 ND2 ASN 188 15242 9042 12011 -5688 1495 -952 N ATOM 1757 N GLN B 184 93.343 -62.868 -18.802 1.00 78.87 N ATOM 1802 C ASN ] i 188 87.975 -68.102 -12.793 1.00 92.41 C ANISOU 1757 N GLN B 184 10212 8569 11186 -3535 2878 -4333 N ANISOU 1802 C ASN 188 13016 10654 11441 -4832 639 -96 C ATOM 1758 CA GLN B 184 93.341 -64.069 -19.605 1.00 85.17 C ATOM 1803 O ASN ] i 188 86.952 -68.334 -12.154 1.00 99.12 O ANISOU 1758 CA GLN B 184 11274 9246 11841 -3808 3136 -4548 C ANISOU 1803 O ASN B 188 13664 11930 12066 -5111 417 90 O ATOM 1759 CB GLN B 184 94.504 -64.036 -20.592 1.00 97.79 C ATOM 1804 N LEU ] i 189 89.025 -67.482 -12.285 1.00 91.36 N ANISOU 1759 CB GLN B 184 13110 10828 13216 -3912 3457 -4694 C ANISOU 1804 N LEU I 189 12723 10330 11660 -4319 752 -100 N ATOM 1760 CG GLN B 184 94.217 -64.700 -21.911 1.00109.17 C ATOM 1805 CA LEU I B 189 89.099 -67.114 -10.889 1.00 91.12 C ANISOU 1760 CG GLN B 184 14922 12307 14250 -4407 3569 -4924 C ANISOU 1805 CA LEU 189 12298 10538 11785 -4074 631 112 C ATOM 1761 CD GLN B 184 93.268 -63.878 -22.753 1.00112.28 C ATOM 1806 CB LEU I i 189 90.559 -66.931 -10.505 1.00 86.21 C ANISOU 1761 CD GLN B 184 15483 13020 14159 -4810 3025 -4846 C ANISOU 1806 CB LEU B 189 11687 9468 11601 -3612 821 76 C ATOM 1762 OE1 GLN B 184 92.870 -62.776 -22.364 1.00114.09 O ATOM 1807 CG LEU B 189 90.891 -66.449 -9.106 1.00 82.39 C ANISOU 1762 OE1 GLN B 184 15502 13424 14423 -4690 2577 -4626 O ANISOU 1807 CG LEU B 189 10809 9204 11293 -3339 735 274 C ATOM 1763 NE2 GLN B 184 92.900 -64.404 -23.915 1.00 99.14 N ATOM 1808 CD1 LEU I ! 189 90.139 -67.276 -8.079 1.00 70.59 C ANISOU 1763 NE2 GLN B 184 14184 11416 12068 -5319 3038 -4994 N ANISOU 1808 CD1 LEU 189 9220 7907 9694 -3682 526 516 C ATOM 1764 C GLN B 184 93.504 -65.273 -18.704 1.00 82.18 C ATOM 1809 CD2 LEU I ! 189 92.385 -66.577 -8.912 1.00 77.56 C ANISOU 1764 C GLN B 184 10785 8565 11874 -3596 3451 -4557 C ANISOU 1809 CD2 LEU 189 10292 8070 11108 -2975 929 251 C ATOM 1765 O GLN B 184 92.702 -66.206 -18.724 1.00 85.55 O ATOM 1810 C LEU I ! 189 88.345 -65.821 -10.658 1.00 88.18 C ANISOU 1765 O GLN B 184 11272 8913 12321 -3774 3452 -4642 O ANISOU 1810 C LEU 189 11466 10834 11204 -3928 487 179 C ATOM 1766 N HIS B 185 94.555 -65.236 -17.900 1.00 78.95 N ATOM 1811 O LEU ] i 189 87.726 -65.612 -9.615 1.00 91.88 O ANISOU 1766 N HIS B 185 10212 7980 11805 -3235 3671 -4433 N ANISOU 1811 O LEU 189 11584 11729 11599 -3960 326 352 O ATOM 1767 C HB B 185 94.223 -66.709 -15.909 1.00100.85 C ATOM 1812 N LEU ] i 190 88.407 -64.944 -11.647 1.00 81.52 N

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c

 NZ N ANISOU 2127 C ILE B 230 11003 8961 13729 1363 2158 -2282

C ATOM 2128 O ILE B 230 114.834 -52.194 -15.044 1.00 84.49 C ANISOU 2128 O ILE B 230 10391 8183 13527 1275 2088 -2076 O ATOM 2129 CB ILE B 230 111.848 -51.128 -15.165 1.00 98.08

O ANISOU 2129 CB ILE B 230 12833 10318 14114 1711 1912 -1660 C N N ATOM 2130 CGI ILE B 230 110.335 -51.236 -15.323 1.00 97.19 C

N N ANISOU 2130 CGI ILE B 230 12803 10352 13772 1933 1793 -1609 C

C ATOM 2131 CG2 ILE B 230 112.318 -49.949 -15.991 1.00 93.96 C C ANISOU 2131 CG2 ILE B 230 12738 9999 12964 1605 2108 -1725 C C ATOM 2132 CD1 ILE B 230 109.891 -51.216 -16.779 1.00 91.06 C C ANISOU 2132 CD1 ILE B 230 12085 9855 12659 1942 1923 -1964 C C ATOM 2133 N ASP B 231 114.292 -52.030 -17.233 1.00102.37 N C ANISOU 2133 N ASP B 231 12776 10940 15182 1241 2396 -2688 N CD1 C ATOM 2134 CA ASP B 231 115.650 -51.931 -17.750 1.00121.49 C

CD1 C ANISOU 2134 CA ASP B 231 15077 13362 17720 988 2623 -3002 C

C ATOM 2135 CB ASP B 231 115.845 -53.015 -18.803 1.00134.17 C C ANISOU 2135 CB ASP B 231 16187 15055 19738 880 2778 -3621 C C ATOM 2136 CG ASP B 231 114.577 -53.277 -19.606 1.00142.54 C C ANISOU 2136 CG ASP B 231 17298 16375 20487 1000 2765 -3768 C O ATOM 2137 OD1 ASP B 231 114.134 -52.374 -20.351 1.00145.88 O O ANISOU 2137 OD1 ASP B 231 18169 17105 20155 960 2858 -3736 O N N ATOM 2138 OD2 ASP B 231 114.017 -54.387 -19.486 1.00142.66 O

N N ANISOU 2138 OD2 ASP B 231 16903 16276 21024 1126 2640 -3899 O

C ATOM 2139 C ASP B 231 115.924 -50.573 -18.399 1.00123.54 C C ANISOU 2139 C ASP B 231 15884 13889 17166 855 2805 -2952 C C ATOM 2140 O ASP B 231 115.877 -50.446 -19.620 1.00131.14 O C ANISOU 2140 O ASP B 231 16914 15143 17771 718 2991 -3301 O I i C ATOM 2141 N ARG B 232 116.224 -49.560 -17.596 1.00111.30 N B C ANISOU 2141 N ARG B 232 14723 12246 15320 866 2744 -2519 N I i C ATOM 2142 CA ARG B 232 116.472 -48.236 -18.151 1.00107.25 C B C ANISOU 2142 CA ARG B 232 14743 11956 14053 741 2879 -2429 C i C ATOM 2143 CB ARG B 232 115.217 -47.376 -18.073 1.00 97.93 C

C ANISOU 2143 CB ARG B 232 14039 10899 12270 942 2724 -2072 C O ATOM 2144 CG ARG I 3 232 114.249 -47.566 -19.209 1.00104.03 C O ANISOU 2144 CG ARG B 232 14847 11947 12732 976 2737 -2309 C N ATOM 2145 CD ARG I 3 232 112.938 -46.921 -18.845 1.00115.18 C N ANISOU 2145 CD ARG B 232 16616 13382 13764 1232 2520 -1930 C C ATOM 2146 NE ARG I 3 232 112.423 -46.043 -19.890 1.00122.63 N i C ANISOU 2146 NE ARG B 232 17976 14596 14022 1172 2527 -1934 N

C ATOM 2147 CZ ARG I i 232 112.880 -44.818 -20.135 1.00121.90 C C ANISOU 2147 CZ ARG B 232 18338 14581 13396 1030 2564 -1760 C C ATOM 2148 NHl ARG B 232 113.880 -44.324 -19.417 1.00117.50 N i C ANISOU 2148 NHl ARG B 232 17878 13865 12904 945 2629 -1591 N

C ATOM 2149 NH2 ARG B 232 112.343 -44.091 -21.106 1.00122.16 N i C ANISOU 2149 NH2 ARG B 232 18730 14846 12840 957 2517 -1741 N

O ATOM 2150 C ARG B 232 117.612 -47.519 -17.455 1.00104.78 C 3 O ANISOU 2150 C ARG B 232 14599 11483 13729 612 2927 -2205 C

N ATOM 2151 O ARG I 3 232 118.258 -48.073 -16.571 1.00111.40 O 3 N ANISOU 2151 O ARG B 232 15127 12039 15159 603 2858 -2134 O

C ATOM 2152 N ALA I 3 233 117.855 -46.279 -17.862 1.00 91.19 N C ANISOU 2152 N ALA I B 233 13375 9937 11337 497 3024 -2080 N O ATOM 2153 CA ALA ] B 233 118.847 -45.460 -17.190 1.00 86.90 C ί 227 O ANISOU 2153 CA ALA i 233 13059 9258 10699 387 3062 -1827 C

N ATOM 2154 CB ALA B 233 119.032 -44.144 -17.911 1.00 84.49 C ί 228 N ANISOU 2154 CB ALA B 233 13295 9192 9615 234 3173 -1754 C i C ATOM 2155 C ALA B 233 118.366 -45.223 -15.772 1.00 88.14 C

C ANISOU 2155 C ALA B 233 13341 9172 10975 602 2829 -1325 C i C ATOM 2156 O ALA B 233 117.165 -45.093 -15.530 1.00 83.02 O

C ANISOU 2156 O ALA B 233 12850 8559 10137 818 2670 -1118 O i C ATOM 2157 N GLY B 234 119.304 -45.195 -14.831 1.00 87.94 N

C ANISOU 2157 N GLY B 234 13227 8908 11276 521 2810 -1148 N i C ATOM 2158 CA GLY B 234 118.976 -44.946 -13.441 1.00 80.20 C

C ANISOU 2158 CA GLY B 234 12367 7718 10386 650 2606 -678 C O ATOM 2159 C GLY B 234 118.126 -46.036 -12.825 1.00 79.87 C O ANISOU 2159 C GLY B 234 11966 7546 10835 813 2403 -625 C N ATOM 2160 O GLY B 234 117.729 -45.959 -11.663 1.00 80.49 O N ANISOU 2160 O GLY B 234 12106 7480 10995 891 2226 -257 O

108.881 -55.565 -14.001 1.00 84.86 C ATOM 2161 N ILE B 235 117.842 -47.072 -13.595 1.00 88.05 N C GLN B 228 9704 8308 14231 2110 1226 -1792 C ANISOU 2161 N ILE B 235 12617 8643 12196 839 2430 -1002 N O GLN B 228 108.990 -54.751 -13.088 1.00 93.99 O ATOM 2162 CA ILE B 235 117.014 -48.135 -13.071 1.00 91.27 C O GLN B 228 11170 9413 15129 2084 1171 -1409 O ANISOU 2162 CA ILE B 235 12679 8930 13068 985 2228 -959 C N THR B 229 109.927 -56.140 -14.573 1.00 81.28 N ATOM 2163 CB ILE B 235 115.506 -47.840 -13.313 1.00110.98 C N THR B 229 8919 7752 14212 1970 1333 -2136 N ANISOU 2163 CB ILE B 235 15428 11625 15114 1207 2153 -867 C CA THR B 229 111.269 -55.713 -14.242 1.00 79.42 C ATOM 2164 CGI ILE B 235 114.640 -48.518 -12.260 1.00107.58 C CA THR B 229 8718 7358 14101 1788 1407 -2073 C ANISOU 2164 CGI ILE B 235 14805 11050 15020 1343 1912 -620 C CB THR B 229 112.264 -56.862 -14.382 1.00 88.46 C ATOM 2165 CD1 ILE B 235 113.213 -48.646 -12.691 1.00107.37 C CB THR B 229 9283 8254 16076 1643 1380 -2385 C ANISOU 2165 CD1 ILE B 235 14840 11203 14752 1554 1850 -676 C OG1 THR B 229 111.609 -58.094 -14.065 1.00 90.20 O ATOM 2166 CG2 ILE B 235 115.066 -48.185 -14.725 1.00119.64 C OG1 THR B 229 9155 8442 16676 1623 1099 -2312 O ANISOU 2166 CG2 ILE B 235 16435 12963 16059 1231 2277 -1288 C CG2 THR B 229 113.443 -56.660 -13.447 1.00 91.06 C ATOM 2167 C ILE B 235 117.501 -49.495 -13.578 1.00 94.55 C CG2 THR B 229 9568 8289 16742 1483 1301 -2139 C ANISOU 2167 C ILE B 235 12492 9244 14190 907 2256 -1387 C C THR B 229 111.603 -54.609 -15.226 1.00 88.04 C ATOM 2168 O ILE B 235 117.456 -49.810 -14.766 1.00101.51 O C THR B 229 10206 8714 14530 1741 1685 -2244 C ANISOU 2168 O ILE B 235 13240 10311 15018 875 2421 -1819 O O THR B 229 111.261 -54.708 -16.401 1.00 94.87 O ATOM 2169 N LYS B 236 118.042 -50.288 -12.671 1.00 86.81 N O THR B 229 11060 9814 15174 1759 1837 -2606 O ANISOU 2169 N LYS B 236 11134 7955 13894 846 2089 -1276 N N FLE B 230 112.244 -53.545 -14.759 1.00 83.19 N ATOM 2170 CA LYS I 3 236 118.524 -51.584 -13.090 1.00 97.56 C N FLE B 230 9957 8078 13574 1659 1740 -1975 N ANISOU 2170 CA LYS B 236 11887 9165 16015 781 2082 -1684 C CA ILE B 230 112.514 -52.424 -15.652 1.00 90.88 C ATOM 2171 CB LYS I i 236 120.056 -51.633 -13.158 1.00100.49 C CA FLE B 230 11349 9303 13879 1597 1969 -2085 C ANISOU 2171 CB LYS B 236 12033 9365 16784 563 2199 -1882 C C FLE B 230 113.997 -52.207 -15.947 1.00 88.68 C ATOM 2172 CG LYS I 3 236 120.764 -52.015 -11.878 1.00102.42 C ANISOU 2172 CG LYS B 236 12047 9225 17641 473 1947 -1550 C ANISOU 2217 CA SERB 241 10488 8519 13613 2346 443 -111 ATOM 2173 CD LYS B 236 122.237 -51.735 -12.014 1.00 99.28 C ATOM 2218 CB SER B 241 104.354 -55.608 -7.596 1.00 93.06 ANISOU 2173 CD LYS B 236 11554 8711 17458 268 2098 -1720 C ANISOU 2218 CB SER B 241 11102 9260 14999 2131 199 146 ATOM 2174 CE LYS B 236 122.893 -52.677 -13.013 1.00102.27 C ATOM 2219 OG SERB 241 104.571 -54.861 -6.416 1.00 98.91 ANISOU 2174 CE LYS B 236 11372 9042 18445 180 2252 -2368 C ANISOU 2219 OG SER B 241 12095 9981 15507 1955 171 497 ATOM 2175 NZ LYS B 236 124.104 -52.048 -13.607 1.00100.60 N ATOM 2220 C SER B 241 103.155 -53.700 -8.629 1.00 76.19 ANISOU 2175 NZ LYS B 236 11226 8914 18084 -19 2544 -2656 N ANISOU 2220 C SER B 241 9620 7508 11821 2511 498 -33 ATOM 2176 C LYS B 236 117.947 -52.672 -12.213 1.00 95.84 C ATOM 2221 O SER B 241 103.314 -52.613 -8.082 1.00 77.14 ANISOU 2176 C LYS B 236 11304 8705 16406 865 1771 -1495 C ANISOU 2221 O SER B 241 10080 7654 11575 2472 568 159 ATOM 2177 O LYS B 236 117.988 -52.590 -10.981 1.00 98.10 O ATOM 2222 N ASN B 242 101.987 -54.102 -9.103 1.00 70.47 ANISOU 2177 O LYS B 236 11653 8794 16827 831 1549 -1045 O ANISOU 2222 N ASN B 242 8796 6924 11055 2696 462 -197 ATOM 2178 N ASP B 237 117.362 -53.662 -12.879 1.00 91.49 N ATOM 2223 CA ASN B 242 100.792 -53.321 -8.885 1.00 60.34 ANISOU 2178 N ASP B 237 10392 8194 16174 953 1757 -1838 N ANISOU 2223 CA ASN B 242 7773 5817 9337 2856 480 -145 ATOM 2179 CA ASP B 237 116.823 -54.837 -12.225 1.00 95.99 C ATOM 2224 CB ASN B 242 100.332 -52.679 -10.187 1.00 66.79 ANISOU 2179 CA ASP B 237 10555 8538 17379 1017 1462 -1731 C ANISOU 2224 CB ASN B 242 8805 6785 9789 3099 593 -386 ATOM 2180 CB ASP B 237 117.963 -55.762 -11.807 1.00105.52 C ATOM 2225 CG ASN B 242 101.357 -51.718 -10.743 1.00 70.58 ANISOU 2180 CB ASP B 237 11221 9356 19516 857 1313 -1829 C ANISOU 2225 CG ASN B 242 9583 7239 9997 3061 738 -396 ATOM 2181 CG ASP B 237 118.515 -56.561 -12.968 1.00114.21 C ATOM 2226 OD1 ASN B 242 102.406 -52.133 -11.239 1.00 78.16 ANISOU 2181 CG ASP B 237 11859 10529 21005 772 1468 -2438 C ANISOU 2226 OD1 ASN B 242 10406 8115 11175 2943 798 -509 ATOM 2182 OD1 ASP B 237 119.007 -55.946 -13.939 1.00116.12 O ATOM 2227 ND2 ASN B 242 101.072 -50.423 -10.647 1.00 53.57 ANISOU 2182 OD1 ASP B 237 12245 10939 20936 734 1816 -2821 O ANISOU 2227 ND2 ASN B 242 7821 5147 7387 3149 791 -289 ATOM 2183 OD2 ASP B 237 118.452 -57.806 -12.904 1.00115.88 O ATOM 2228 C ASN B 242 99.697 -54.184 -8.290 1.00 67.60 ANISOU 2183 OD2 ASP B 237 11579 10673 21775 691 1231 -2518 O ANISOU 2228 C ASN B 242 8435 6790 10460 2860 327 -112 ATOM 2184 C ASP B 237 115.963 -54.475 -11.023 1.00 93.55 C ATOM 2229 O ASN B 242 99.581 -55.360 -8.615 1.00 74.28 ANISOU 2184 C ASP B 237 10545 8208 16791 1088 1228 -1161 C ANISOU 2229 O ASN B 242 8928 7591 11703 2855 227 -237 ATOM 2185 O ASP B 237 116.207 -54.932 -9.908 1.00 99.80 O ATOM 2230 N SER B 243 98.902 -53.594 -7.408 1.00 59.32 ANISOU 2185 O ASP B 237 11156 8727 18037 987 959 -834 O ANISOU 2230 N SER B 243 5998 7665 8876 -134 596 -1377 ATOM 2186 N ARG B 238 114.980 -53.616 -11.250 1.00 76.68 N ATOM 2231 CA SER B 243 97.854 -54.342 -6.739 1.00 52.84 ANISOU 2186 N ARG B 238 8868 6365 13904 1233 1326 -1049 N ANISOU 2231 CA SERB 243 5275 6302 8498 -89 391 -1463 ATOM 2187 CA ARG B 238 114.047 -53.272 -10.197 1.00 69.59 C ATOM 2232 CB SER B 243 97.819 -54.017 -5.251 1.00 63.15 ANISOU 2187 CA ARG B 238 8230 5488 12724 1303 1143 -593 C ANISOU 2232 CB SER B 243 6853 7101 10042 -341 337 -985 ATOM 2188 CB ARG B 238 113.797 -51.777 -10.156 1.00 70.10 C ATOM 2233 OG SERB 243 98.998 -54.463 -4.620 1.00 81.25 ANISOU 2188 CB ARG B 238 8899 5768 11970 1357 1293 -387 C ANISOU 2233 OG SER B 243 8983 9267 12621 -373 290 -958 ATOM 2189 CG ARG I 3 238 113.268 -51.311 -8.833 1.00 67.37 C ATOM 2234 C SER B 243 96.496 -54.082 -7.360 1.00 52.84 ANISOU 2189 CG ARG B 238 8794 5384 11420 1340 1128 88 C ANISOU 2234 C SER B 243 5421 6386 8269 0 386 -1569 ATOM 2190 CD ARG I 3 238 114.172 -50.240 -8.288 1.00 67.24 C ATOM 2235 O SER B 243 96.218 -52.994 -7.853 1.0046.24 ANISOU 2190 CD ARG B 238 9114 5316 11119 1201 1207 333 C ANISOU 2235 O SER B 243 4794 5862 6914 -48 535 -1365 ATOM 2191 NE ARG I 3 238 113.574 -48.918 -8.410 1.00 63.62 N ATOM 2236 N ILE B 244 95.648 -55.100 -7.313 1.00 57.53 ANISOU 2191 NE ARG B 238 9181 5075 9916 1321 1339 443 N ANISOU 2236 N ILE B 244 5912 6686 9261 126 197 -1892 ATOM 2192 CZ ARG I i 238 114.216 -47.781 -8.173 1.00 63.81 C ATOM 2237 CA ILE B 244 94.307 -55.003 -7.852 1.00 47.95 ANISOU 2192 CZ ARG B 238 9576 5108 9561 1242 1449 608 C ANISOU 2237 CA ILE B 244 4775 5545 7897 219 155 -2054 ATOM 2193 NHl ARG B 238 115.486 -47.803 -7.798 1.00 56.77 N ATOM 2238 CB ILE B 244 93.994 -56.186 -8.741 1.00 59.70 ANISOU 2193 NHl ARG B 238 8595 4035 8939 1040 1456 687 N ANISOU 2238 CB ILE B 244 5947 7103 9633 489 -9 -2687 ATOM 2194 NH2 ARG B 238 113.581 -46.627 -8.301 1.00 56.26 N ATOM 2239 CGI ILE B 244 95.138 -56.437 -9.710 1.00 59.82 ANISOU 2194 NH2 ARG B 238 9066 4324 7986 1366 1534 696 N ANISOU 2239 CGI ILE B 244 5691 7571 9467 715 53 -3013 ATOM 2195 C ARG B 238 112.755 -53.993 -10.487 1.00 74.07 C ATOM 2240 CD1 ILE B 244 94.917 -57.652 -10.559 1.00 51.94 ANISOU 2195 C ARG B 238 8637 6168 13339 1476 1049 -705 C ANISOU 2240 CD1 ILE B 244 4391 6621 8723 1029 -151 -3677 ATOM 2196 O ARG I 3 238 112.357 -54.119 -11.642 1.00 85.97 O ATOM 2241 CG2 ILE B 244 92.718 -55.944 -9.514 1.00 58.22 ANISOU 2196 O ARG B 238 10111 7866 14689 1589 1203 -1072 O ANISOU 2241 CG2 ILE B 244 5802 7137 9183 615 -34 -2897 ATOM 2197 N VAL I 3 239 112.097 -54.476 -9.444 1.00 71.98 N ATOM 2242 C ILE B 244 93.309 -54.994 -6.713 1.00 55.72 ANISOU 2197 N VAL BI 239 8273 5800 13277 1468 795 -389 N ANISOU 2242 C ILE B 244 5976 6044 9152 34 63 -1760 ATOM 2198 CA VAL B 1 239 110.855 -55.194 -9.649 1.00 62.35 C ATOM 2243 O ILE B 244 93.399 -55.805 -5.795 1.00 51.52 ANISOU 2198 CA VAL B 239 6889 4681 12121 1622 693 -481 C ANISOU 2243 O ILE B 244 5395 5043 9138 -61 -66 -1717 ATOM 2199 CB VAL I S 239 110.853 -56.539 -8.930 1.00 72.47 C ATOM 2244 N TYR B 245 92.347 -54.083 -6.785 1.00 50.99 ANISOU 2199 CB VAL BI 239 7681 5695 14160 1514 389 -375 C ANISOU 2244 N TYR B 245 5619 5579 8177 7 126 -1559 ATOM 2200 CGI VAL I B 239 109.843 -57.459 -9.577 1.00 60.93 C ATOM 2245 CA TYR B 245 91.394 -53.921 -5.705 1.00 43.63 ANISOU 2200 CGI VAL S 239 5949 4333 12869 1671 341 -642 C ANISOU 2245 CA TYR B 245 4887 4286 7404 -146 65 -1248 ATOM 2201 CG2 VAL B 239 112.238 -57.155 -8.999 1.00 62.14 C ATOM 2246 CB TYR B 245 91.556 -52.555 -5.060 1.00 46.69 ANISOU 2201 CG2 VAL B 239 5996 4110 13503 1330 337 -514 C ANISOU 2246 CB TYR B 245 5658 4697 7385 -282 186 -699 ATOM 2202 C VAL B 239 109.682 -54.350 -9.201 1.00 60.71 C ATOM 2247 CG TYR B 245 92.882 -52.387 -4.376 1.00 52.34 ANISOU 2202 C VAL B 239 7100 4692 11273 1747 694 -224 C ANISOU 2247 CG TYR B 245 6424 5253 8211 -437 236 -414 ATOM 2203 O VAL B 239 109.561 -53.997 -8.030 1.00 56.77 O ATOM 2248 CD1 TYR B 245 93.999 -51.957 -5.082 1.00 52.62 ANISOU 2203 O VAL B 239 6760 4141 10669 1644 570 158 O ANISOU 2248 CD1 TYR B 245 6403 5628 7963 -431 361 -440 ATOM 2204 N TYR B 240 108.834 -54.006 -10.159 1.00 66.99 N ATOM 2249 CE1 TYR B 245 95.220 -51.810 -4.457 1.00 50.43 ANISOU 2204 N TYR B 240 8067 5736 11648 1951 835 -454 N ANISOU 2249 CE1 TYR B 245 6125 5243 7794 -586 398 -203 ATOM 2205 CA TYR B 240 107.634 -53.246 -9.878 1.00 69.02 C ATOM 2250 CZ TYR B 245 95.329 -52.102 -3.108 1.00 52.64 ANISOU 2205 CA TYR B 240 8675 6191 11359 2103 831 -281 C ANISOU 2250 CZ TYR B 245 6490 5050 8461 -712 296 54 ATOM 2206 CB TYR B 240 107.432 -52.162 -10.924 1.00 72.04 C ATOM 2251 OH TYR B 245 96.537 -51.964 -2.470 1.00 59.11 ANISOU 2206 CB TYR B 240 9444 6795 11133 2244 1037 -447 C ANISOU 2251 OH TYR B 245 7297 5774 9387 -843 310 263 ATOM 2207 CG TYR B 240 108.358 -50.991 -10.766 1.00 69.93 C ATOM 2252 CE2 TYR B 245 94.231 -52.535 -2.389 1.00 56.61 ANISOU 2207 CG TYR B 240 9539 6506 10527 2141 1164 -300 C ANISOU 2252 CE2 TYR B 245 7076 5202 9232 -706 183 106 ATOM 2208 CD1 TYR B 240 108.059 -49.967 -9.876 1.00 56.94 C ATOM 2253 CD2 TYR B 245 93.019 -52.678 -3.024 1.00 56.85 ANISOU 2208 CD1 TYR B 240 8255 4879 8503 2150 1142 20 C ANISOU 2253 CD2 TYR B 245 7075 5363 9162 -588 160 -124 ATOM 2209 CE1 TYR B 240 108.894 -48.891 -9.728 1.00 62.14 C ATOM 2254 C TYR B 245 89.956 -54.115 -6.141 1.00 47.73 ANISOU 2209 CE1 TYR B 240 9245 5510 8856 2058 1253 155 C ANISOU 2254 C TYR B 245 5349 4896 7889 -43 -19 -1499 ATOM 2210 CZ TYR B 240 110.050 -48.823 -10.475 1.00 64.12 C ATOM 2255 O TYR B 245 89.575 -53.781 -7.257 1.00 49.86 ANISOU 2210 CZ TYR B 240 9475 5727 9161 1945 1390 -24 C ANISOU 2255 O TYR B 245 5585 5585 7774 151 13 -1766 ATOM 2211 OH TYR B 240 110.883 -47.744 -10.325 1.00 56.47 O ATOM 2256 N GLU B 246 89.174 -54.667 -5.227 1.00 50.03 ANISOU 2211 OH TYR B 240 8842 4735 7878 1845 1497 118 O ANISOU 2256 N GLU B 246 5620 4809 8581 -179 -125 -1402 ATOM 2212 CE2 TYR B 240 110.373 -49.834 -11.369 1.00 69.67 C ATOM 2257 CA GLU I 3 246 87.739 -54.776 -5.381 1.0048.26 ANISOU 2212 CE2 TYR B 240 9809 6426 10237 1920 1430 -368 C ANISOU 2257 CA GLU B 246 5333 4659 8344 -146 -199 -1555 ATOM 2213 CD2 TYR B 240 109.530 -50.905 -11.509 1.00 65.13 C ATOM 2258 CB GLU I i 246 87.264 -56.047 -4.695 1.00 70.53 ANISOU 2213 CD2 TYR B 240 8898 5865 9981 2022 1317 -507 C ANISOU 2258 CB GLU B 246 7940 7024 11833 -315 -351 -1658 ATOM 2214 C TYR B 240 106.417 -54.151 -9.862 1.00 78.62 C ATOM 2259 CG GLU I 3 246 85.778 -56.266 -4.698 1.00 86.28 ANISOU 2214 C TYR B 240 9642 7469 12760 2226 687 -345 C ANISOU 2259 CG GLU B 246 9811 9074 13898 -356 -430 -1788 ATOM 2215 O TYR B 240 106.264 -55.027 -10.713 1.00 74.15 O ATOM 2260 CD GLU I 3 246 85.394 -57.518 -3.925 1.00 95.6 ANISOU 2215 O TYR B 240 8772 6917 12485 2293 692 -655 O ANISOU 2260 CD GLU B 246 10856 10003 15495 -497 -511 -1651 ATOM 2216 N SER B 241 105.549 -53.926 -8.888 1.00 79.96 N ATOM 2261 OE1 GLU : B 246 84.559 -58.297 -4.432 1.00101.97 ANISOU 2216 N SER B 241 9938 7688 12755 2238 573 -71 N ANISOU 2261 OE1 GLU B 246 11412 10833 16501 -490 -625 -1986 ATOM 2217 CA SER B 241 104.311 -54.671 -8.795 1.00 85.85 C ATOM 2262 OE2 GLU B 246 85.930 -57.725 -2.814 1.00 83.50



 N GLN 3 276 6058 7444 4534 -229 -856 -781

CA GLN I 3 276 115.070 -27.732 7.277 1.00 42.29

CA GLN B 276 5217 6738 4115 -355 -805 -896 CB GLN I i 276 115.999 -28.931 7.247 1.00 54.96

CB GLN B 276 6516 8463 5903 -244 -967 -863 CG GLN I 3 276 117.382 -28.668 6.744 1.00 74.49

CG GLN B 276 8654 11017 8632 -404 -950 -1128 CD GLN I 3 276 118.296 -29.842 7.011 1.00 92.77

CD B 276 10604 13458 11185 -199 -1234 -1186 OE1 I B 276 117.839 -30.923 7.389 1.00100.03

OE1 GLN B 276 11614 14330 12062 54 -1437 -957 NE2 GLN I 3 276 119.595 -29.637 6.827 1.00 96.97

NE2 GLN B 276 10724 14136 11985 -315 -1276 -1528 C GLN I i 276 114.547 -27.452 5.866 1.00 51.26

C GLN B 276 6495 7638 5343 -415 -563 -861 O GLN I 3 276 115.208 -26.810 5.054 1.00 52.96

O GLN B 276 6718 7759 5644 -651 -442 -985 N ALA I 3 277 113.348 -27.948 5.586 1.00 42.04 i N ALA B I 277 5470 6378 4125 -245 -504 -702 i CA ALA B] 277 112.751 -27.840 4.266 1.00 37.47

CA ALA B 277 5056 5568 3611 -263 -358 -641 3 CB ALA I i 277 111.755 -28.967 4.041 1.00 32.84

CB ALA B 277 4459 4988 3030 -53 -326 -467 C ALA B 277 112.081 -26.488 4.034 1.00 47.35

C ALA B 277 6623 6567 4801 -321 -377 -738 O ALA B 277 111.840 -26.100 2.896 1.00 54.14

O ALA B 277 7722 7166 5683 -409 -338 -701 N GLY B 278 111.765 -25.786 5.118 1.00 63.33

N GLY B 278 8686 8641 6737 -270 -472 -876 CA GLY B 278 111.169 -24.460 5.032 1.00 59.75

CA GLY B 278 8515 7909 6279 -270 -556 -1035 C GLY B 278 109.834 -24.449 4.307 1.00 57.23

C GLY B 278 8354 7353 6039 -50 -612 -1016 O GLY B 278 109.608 -23.669 3.387 1.00 65.52

O GLY B 278 9728 8031 7134 -87 -731 -1019 N PHE B 279 108.933 -25.316 4.747 1.00 62.01

N PHE B 279 8755 8162 6644 156 -558 -1012 CA PHE B 279 107.711 -25.603 4.016 1.0044.23 i CA PHE B 279 6537 5768 4501 363 -597 -1013

CB PHE B 279 107.890 -26.950 3.331 1.00 55.14

CB PHE B 279 7811 7261 5878 332 -468 -750 CG PHE 3 279 106.993 -27.166 2.160 1.00 54.39 i CG PHE ] 279 7832 6949 5885 456 -536 -696

CD1 PHE I 279 107.236 -26.520 0.960 1.00 55.03 i CD1 PHE i 279 8255 6678 5977 357 -665 -618

CE1 PHE B 279 106.423 -26.732 -0.132 1.00 48.80

CE1 PHE B 279 7625 5673 5243 460 -789 -554 CZ PHE B 279 105.356 -27.621 -0.033 1.00 53.59

CZ PHE B 279 7972 6448 5944 678 -756 -601 CE2 PHE B 279 105.113 -28.285 1.162 1.00 50.79

CE2 PHE B 279 7262 6458 5578 733 -570 -692 CD2 PHE B 279 105.934 -28.056 2.246 1.00 49.48

CD2 PHE B 279 7015 6476 5308 616 -474 -720 C PHE B 279 106.577 -25.691 5.020 1.00 45.23

C PHE B 279 6456 6100 4629 538 -556 -1270 O PHE B 279 106.591 -26.547 5.898 1.00 58.42

O PHE B 279 7940 8107 6151 468 -397 -1233 N SER B 280 105.603 -24.798 4.897 1.00 40.10

N SER B 280 5857 5235 4145 744 -716 -1564 CA SER B 280 104.515 -24.734 5.862 1.00 37.26

CA SERB 280 5230 5103 3824 880 -632 -1954 CB SER B 280 104.022 -23.296 6.025 1.00 53.38

CB SER B 280 7352 6860 6071 1082 -868 -2370 OG SER B 280 103.224 -22.914 4.923 1.00 60.97

OG SER B 280 8427 7430 7310 1361 -1175 -2449 C SER B 280 103.347 -25.629 5.454 1.00 40.92

C SER B 280 5468 5685 4395 1017 -553 -2018 O SER B 280 103.287 -26.146 4.337 1.00 58.09

O SER B 280 7734 7693 6643 1067 -634 -1767 N ARG B 281 102.396 -25.774 6.369 1.00 58.87

N ARG B 281 8326 8383 5659 1120 -812 -887 CA ARG B 281 101.235 -26.607 6.123 1.00 70.75

CA ARG B 281 9909 9979 6992 1011 -459 -575 CB ARG B 281 100.511 -26.891 7.427 1.00 86.15

CB ARG B 281 12102 12238 8391 1134 -289 -585 CG ARG I 3 281 100.183 -28.348 7.605 1.00101.97

CG ARG B 281 14348 14284 10112 1060 -6 -192 CD ARG I 3 281 98.703 -28.489 7.883 1.00107.82

CD ARG B 281 15104 15175 10687 949 478 -209 NE ARG I 3 281 98.343 -29.316 9.039 1.00113.76

NE ARG B 281 16275 16081 10868 994 793 -33 CZ ARG I i 281 98.924 -29.303 10.240 1.00119.33

CZ ARG B 281 17373 16937 11029 1244 616 -36 NHl ARG B 281 98.459 -30.105 11.188 1.00126.50

NHl ARG B 281 18751 17936 11376 1272 1003 182 NH2 ARG B 281 99.958 -28.514 10.515 1.00113.49

NH2 ARG B 281 16584 16246 10290 1478 80 -280 C ARG B 281 100.293 -25.943 5.128 1.00 68.75

C ARG B 281 9456 9608 7057 907 -283 -635 O ARG B 281 99.464 -26.594 4.497 1.00 72.07

 ANISOU 2622 CB CYS B 292 3154 4422 3968 357 303 -64 C ANISOU 2667 C ASP B 297 7624 5999 4605 911 105 431 C ATOM 2623 SG CYS I i 292 94.895 -32.847 -9.370 1.00 79.76 S ATOM 2668 O ASP B 297 99.683 -32.037 -19.876 1.00 43.96 O ANISOU 2623 SG CYS B 292 8981 10986 10340 583 230 -545 S ANISOU 2668 O ASP B 297 7470 5518 3715 1101 82 415 o ATOM 2624 C CYS B 292 97.362 -31.736 -10.756 1.00 41.82 C ATOM 2669 N ILE B 298 100.556 -32.636 -17.900 1.00 38.67 N ANISOU 2624 C CYS B ! 292 5080 5620 5188 527 66 119 C ANISOU 2669 N ILE B 298 6094 4715 3883 391 385 510 N ATOM 2625 O CYS B 292 97.132 -32.424 -11.750 1.00 38.69 O ATOM 2670 CA ILE B 298 101.586 -33.463 -18.495 1.00 48.88 C ANISOU 2625 O CYS E ! 292 4542 5349 4808 557 42 -1 3 ANISOU 2670 CA ILE B 298 7292 5937 5342 -9 675 526 c ATOM 2626 N ARG B 293 97.358 -30.416 -10.808 1.00 41.69 N ATOM 2671 CB ILE B 298 102.581 -33.962 -17.452 1.00 40.21 c ANISOU 2626 N ARG I 3 293 5447 5433 4963 780 -89 173 N ANISOU 2671 CB ILE B 298 5832 4677 4769 -495 896 599 c ATOM 2627 CA ARG I B 293 97.061 -29.738 -12.056 1.00 32.22 C ATOM 2672 CGI ILE B 298 103.377 -32.794 -16.890 1.00 44.24 c ANISOU 2627 CA ARG 293 4596 4158 3489 1139 -296 146 C ANISOU 2672 CGI ILE B 298 6739 4786 5285 -599 1050 806 c ATOM 2628 CB ARG B 293 96.725 -28.284 -11.794 1.00 44.75 c ATOM 2673 CD1 ILE B 298 104.380 -33.218 -15.841 1.00 47.74 c ANISOU 2628 CB ARG B 293 6549 5558 4897 1476 -472 154 c ANISOU 2673 CD1 ILE B 298 6823 5098 6218 -988 1172 800 c ATOM 2629 CG ARG I 3 293 95.439 -28.153 -11.064 1.00 54.97 c ATOM 2674 CG2 ILE B 298 103.542 -34.975 -18.072 1.00 40.72 c ANISOU 2629 CG ARG B 293 7486 7128 6272 1718 -644 -196 c ANISOU 2674 CG2 ILE B 298 5678 4708 5086 -879 1145 524 c ATOM 2630 CD ARG I 3 293 95.009 -26.736 -10.991 1.00 91.56 c ATOM 2675 C ILE B 298 100.975 -34.666 -19.207 1.00 46.53 ANISOU 2630 CD ARG B 293 12471 11578 10741 2123 -874 -239 ANISOU 2675 C ILE B 298 6557 6034 5089 56 553 221 ATOM 2631 NE ARG I 3 293 93.968 -26.578 -9.985 1.00108.10 N ATOM 2676 O ILE B 298 101.329 -34.981 -20.343 1.00 58.33 o ANISOU 2631 NE ARG B 293 14167 13912 12993 2243 -956 -594

ATOM 2632 CZ ARG I i 293 94.134 -25.922 -8.844 1.00102.89 C

ANISOU 2632 CZ ARG B 293 13525 13154 12414 2140 -864 -572 C

ATOM 2633 NH1 ARG B 293 93.134 -25.837 -7.980 1.00 99.36 N

ANISOU 2633 NH1 ARG B 293 12707 12948 12095 2237 -896 --993366

ATOM 2634 NH2 ARG B 293 95.298 -25.342 -8.579 1.00 96.55 N

ANISOU 2634 NH2 ARG B 293 13085 12015 11585 1937 -722 --224477

ATOM 2635 C ARG B 293 98.192 -29.847 -13.069 1.00 46.65 C

ANISOU 2635 C ARG B 293 6770 5740 5214 964 -152 399 C

ATOM 2636 O ARG B 293 97.958 -29.937 -14.269 1.00 49.04 o

ANISOU 2636 O ARG B 293 7257 6089 5288 1180 -257 356 o

ATOM 2637 N THR B 294 99.421 -29.834 -12.576 1.00 39.86 N

ANISOU 2637 N THR B 294 5992 4628 4524 587 88 614 N

ATOM 2638 CA THR B 294 100.570 -29.946 -13.452 1.0042.36 C

ANISOU 2638 CA THR B 294 6579 4688 4829 351 302 785 c

ATOM 2639 CB THR B 294 101.872 -29.689 -12.707 1.00 42.27 c

ANISOU 2639 CB THR B 294 6601 4379 5080 -15 524 900 c

ATOM 2640 OG1 THR B 294 101.811 -28.405 -12.076 1.00 44.36 o

ANISOU 2640 OG1 THR B 294 7136 4429 5288 137 480 925 o

ATOM 2641 CG2 THR B 294 103.044 -29.736 -13.679 1.00 30.60 c

ANISOU 2641 CG2 THR B 294 5380 2605 3641 -283 807 994 c

ATOM 2642 C THR B 294 100.628 -31.335 -14.075 1.00 36.59 c

ANISOU 2642 C THR B 294 5498 4188 4215 170 364 697 c

ATOM 2643 O THR B 294 100.810 -31.497 -15.282 1.00 32.95 o

ANISOU 2643 O THR B 294 5247 3700 3571 210 411 709 o

ATOM 2644 N LEU B 295 100.465 -32.338 -13.228 1.00 36.55 N

ANISOU 2644 N LEU B 295 4990 4393 4505 -21 386 607 N

ATOM 2645 CA LEU B 295 100.498 -33.723 -13.670 1.00 39.13 c

ANISOU 2645 CA LEU B 295 4931 4902 5034 -215 473 503 c

ATOM 2646 CB LEU B 295 100.369 -34.661 -12.482 1.00 29.39 c

ANISOU 2646 CB LEU B 295 3269 3781 4117 -417 555 477 c

ATOM 2647 CG LEU B 295 100.553 -36.124 -12.854 1.00 38.69 c

ANISOU 2647 CG LEU B 295 4066 5051 5583 -658 696 396 c

ATOM 2648 CD1 LEU I 3 295 101.923 -36.352 -13.491 1.00 26.99 c

ANISOU 2648 CD1 LEU B 295 2700 3346 4209 -917 811 510 c

ATOM 2649 CD2 LEU I 3 295 100.389 -36.970 -11.616 1.0044.70 c

ANISOU 2649 CD2 LEU B 295 4571 5848 6566 -802 795 419 c

ATOM 2650 C LEU 3 295 99.375 -34.009 -14.669 1.00 39.86 c

ANISOU 2650 C LEU B 295 4910 5282 4953 89 305 246 c ANISOU 2695 OD2 ASP B 301 17679 18710 15746 1703 1338 3888 ATOM 2651 O LEU I 3 295 99.567 -34.678 -15.681 1.0042.15 o ATOM 2696 C ASP B 301 100.867 -35.309 -24.052 1.00 68.04 C ANISOU 2651 O LEU B 295 5131 5649 5234 30 348 159 o ANISOU 2696 C ASP B 301 9504 10022 6326 450 772 1969 C ATOM 2652 N GLU I B 296 98.193 -33.504 -14.343 1.00 37.31 N ATOM 2697 O ASP B 301 101.744 -35.222 -24.901 1.00 69.68 O ANISOU 2652 N GLU 3 296 4526 5135 4515 430 94 60 N ANISOU 2697 O ASP B 301 9894 10156 6424 447 1058 1983 o ATOM 2653 CA GLU I 3 296 97.043 -33.523 -15.237 1.00 40.92 c ATOM 2698 N ALA B 302 100.749 -36.360 -23.252 1.00 63.48 N ANISOU 2653 CA GLU B 296 4887 5872 4789 840 -170 -280 c ANISOU 2698 N ALA B 302 9022 9214 5884 226 694 1496 N ATOM 2654 CB GLU I i 296 95.962 -32.623 -14.645 1.00 42.77 c ATOM 2699 CA ALA B 302 101.793 -37.372 -23.222 1.00 55.49 C ANISOU 2654 CB GLU B 296 5128 6196 4926 1218 -410 -463 c ANISOU 2699 CA ALA B 302 8307 7738 5038 43 984 1020 c ATOM 2655 CG GLU I 3 296 94.609 -32.687 -15.281 1.00 59.21 c ATOM 2700 CB ALA B 302 102.111 -37.772 -21.798 1.0047.46 c ANISOU 2655 CG GLU B 296 6952 8611 6933 1681 -740 -956 c ANISOU 2700 CB ALA B 302 7267 6152 4613 166 966 807 c ATOM 2656 CD GLU I 3 296 93.714 -31.549 -14.808 1.00 84.41 c ATOM 2701 C ALA B 302 101.481 -38.602 -24.060 1.00 75.31 c ANISOU 2656 CD GLU B 296 10262 11814 9996 2108 -1019 -1120 ANISOU 2701 C ALA B 302 11032 10603 6979 -459 1074 596 c ATOM 2657 OE1 GLU : B 296 92.542 -31.498 -15.245 1.00101.08 ATOM 2702 O ALA I 3 302 100.387 -39.166 -23.968 1.00 68.11 o ANISOU 2657 OE1 GLU B 296 12123 14202 12082 2552 -1352 -1610 ANISOU 2702 O ALA B 302 10038 10099 5741 -734 852 429 o ATOM 2658 OE2 GLU B 296 94.182 -30.705 -14.009 1.00 63.58 O ATOM 2703 N PRO I i 303 102.461 -39.025 -24.875 1.00 72.71 N ANISOU 2658 OE2 GLU B 296 7932 8913 7312 2017 -925 -817 o ANISOU 2703 N PRO I B 303 10970 10095 6561 -611 1451 375 N ATOM 2659 C GLU B 296 97.437 -33.006 -16.631 1.00 45.45 c ATOM 2704 CA PRO I B 303 102.386 -40.233 -25.702 1.00 83.59 c ANISOU 2659 C GLU B 296 5996 6334 4937 1072 -280 -174 c ANISOU 2704 CA PRO i 303 12597 11691 7471 -1141 1690 -136 ATOM 2660 O GLU I 3 296 97.088 -33.592 -17.657 1.00 48.51 o ATOM 2705 CB PRO B 303 103.795 -40.341 -26.288 1.00 80.66 ANISOU 2660 O GLU B 296 6273 6946 5214 1228 -396 -409 o ANISOU 2705 CB PRO B 303 12489 10851 7309 -1108 2173 -249 ATOM 2661 N ASP 3 297 98.177 -31.903 -16.653 1.00 43.27 N ATOM 2706 CG PRO I i 303 104.287 -38.935 -26.330 1.00 59.10 ANISOU 2661 N ASP I B 297 6326 5693 4420 1090 -206 164 N ANISOU 2706 CG PRO B 303 9612 8042 4802 -634 2103 304 ATOM 2662 CA ASP 1 B 297 98.568 -31.261 -17.900 1.00 50.57 c ATOM 2707 CD PRO I i 303 103.714 -38.282 -25.102 1.00 62.98 ANISOU 2662 CA ASP i 297 7916 6416 4881 1307 -213 329 c ANISOU 2707 CD PRO B 303 9802 8431 5696 -297 1728 593 ATOM 2663 CB ASP B 297 99.013 -29.820 -17.655 1.00 51.85 c ATOM 2708 C PRO B 303 102.076 -41.481 -24.880 1.00 84.86 ANISOU 2663 CB ASP B 297 8731 6133 4835 1408 -133 641 c ANISOU 2708 C PRO B 303 12825 11533 7883 -1385 1768 -602 ATOM 2664 CG ASP B 297 97.857 -28.851 -17.672 1.00 83.05 c ATOM 2709 O PRO B 303 101.283 -42.301 -25.320 1.00 85.87 o ANISOU 2664 CG ASP B 297 12942 10131 8484 2025 -531 534 c ANISOU 2709 O PRO B 303 13001 12071 7556 -1859 1782 -981 o ATOM 2665 OD1 ASP B 297 96.761 -29.250 -18.119 1.00100.07 o ATOM 2710 N GLU B 304 102.693 -41.627 -23.713 1.00 80.16 N ANISOU 2665 OD1 ASP B 297 14841 12666 10515 2427 -896 194 o ANISOU 2710 N GLU B 304 12216 10251 7992 -1077 1845 -573 N ATOM 2666 OD2 ASP B 297 98.053 -27.689 -17.248 1.00 88.28 o ATOM 2711 CA GLU B 304 102.485 -42.820 -22.894 1.00 83.48 C ANISOU 2666 OD2 ASP B 297 14033 10438 9071 2119 -488 737 ANISOU 2711 CA GLU B 304 12704 10312 8702 -1234 1994 -920 C ATOM 2667 C ASP B 297 99.656 -32.020 -18.651 1.00 47.97 C ATOM 2712 CB GLU B 304 103.617 -42.993 -21.881 1.00 90.31 C ANISOU 2712 CB GLU B 304 13580 10431 10302 -854 2195 -827 C ANISOU 2757 CA ARG B 310 5581 5629 4170 -576 -325 -27 C ATOM 2713 CG GLU I i 304 104.979 -43.214 -22495 1.00102.89 c ATOM 2758 CB ARG B 310 91.988 -42.391 -14.279 1.00 60.53 C ANISOU 2713 CG GLU B 304 15358 11606 12130 -823 2658 -917 c ANISOU 2758 CB ARG B 310 8013 8405 6580 -909 -349 -253 C ATOM 2714 CD GLU I i 304 105.765 -41.926 -22.639 1.00111.99 c ATOM 2759 CG ARG I i 310 90.812 -41.458 -14.239 1.00 81.13 C ANISOU 2714 CD GLU B 304 16390 12722 13438 -459 2539 -550 c ANISOU 2759 CG ARG I 1 310 10263 11443 9119 -853 -674 30 C ATOM 2715 OE1 GLU : B 304 107.009 -42.001 -22.722 1.00119.36 o ATOM 2760 CD ARG B 310 90.295 -41.168 -15.630 1.00 95.03 C ANISOU 2715 OE1 GLU B 304 17383 13195 14773 -305 2870 -556 o ANISOU 2760 CD ARG B 310 11797 13909 10400 -1092 -879 87 C ATOM 2716 OE2 GLU B 304 105.140 -40.843 -22.663 1.00108.90 o ATOM 2761 NE ARG B 310 88.857 -40.939 -15.584 1.00113.74 N ANISOU 2716 OE2 GLU B 304 15823 12733 12821 -323 2164 -251 o ANISOU 2761 NE ARG B 310 13794 16743 12680 -1209 -1119 198 N ATOM 2717 C GLU B 304 101.162 -42.812 -22.137 1.00 81.29 c ATOM 2762 CZ ARG B 310 88.303 -39.768 -15.293 1.00119.62 C ANISOU 2717 C GLU B 304 12218 10345 8325 -1266 1601 -868 c ANISOU 2762 CZ ARG B 310 14230 17634 13584 -893 -1325 681 C ATOM 2718 O GLU B 304 100.667 -43.857 -21.724 1.00 81.38 o ATOM 2763 NH1 ARG B 310 86.982 -39.648 -15.255 1.00119.18 N ANISOU 2718 O GLU B 304 12290 10227 8406 -1515 1740 -1198 o ANISOU 2763 NH1 ARG I 310 13805 17997 13483 -1003 -1516 786 N ATOM 2719 N SER B 305 100.598 -41.628 -21.949 1.00 87.98 N ATOM 2764 NH2 ARG B 310 .072 -38.716 -15.043 1.00120.92 N ANISOU 2719 N SER B 305 12813 11549 9067 -1004 1176 -444 N ANISOU 2764 NH2 ARG B 310 14434 17507 14002 -480 -1292 1045 N ATOM 2720 CA SER B 305 99.522 -41.448 -20.984 1.00 85.33 c ATOM 2765 C ARG B 310 93.660 -41.082 -12.978 1.00 45.85 C ANISOU 2720 CA SERB 305 12252 11352 8819 -913 830 -316 c ANISOU 2765 C ARG B 310 6244 5932 5243 -193 -354 184 C ATOM 2721 CB SER B 305 99.676 -40.106 -20.284 1.00 94.70 c ATOM 2766 O ARG B 310 93.970 -41.807 -12.040 1.00 49.88 O ANISOU 2721 CB SER B 305 13217 12427 10337 -428 585 164 c ANISOU 2766 O ARG B 310 6910 6080 5964 -123 -183 72 o ATOM 2722 OG SERB 305 101.048 -39.772 -20.225 1.00 99.41 o ATOM 2767 N LEU B 311 93.593 -39.762 -12.878 1.0049.02 N ANISOU 2722 OG SER B 305 13620 13590 10560 -382 359 517 o ANISOU 2767 N LEU B 311 6442 6446 5738 48 -534 497 N ATOM 2723 C SER B 305 98.126 -41.470 -21.580 1.00 75.03 c ATOM 2768 CA LEU B 311 93.890 -39.084 -11.631 1.00 43.12 C ANISOU 2723 C SER B 305 10778 10799 6933 -1241 556 -356 c ANISOU 2768 CA LEU B 311 5648 5407 5328 340 -539 622 c ATOM 2724 O SER B 305 97.157 -41.202 -20.876 1.00 77.92 o ATOM 2769 CB LEU B 311 94.539 -37.737 -11.889 1.0044.46 c ANISOU 2724 O SER B 305 10917 11326 7362 -1157 264 -205 o ANISOU 2769 CB LEU B 311 5686 5560 5646 575 -561 862 c ATOM 2725 N GLN B 306 97.999 -41.751 -22.869 1.00 72.67 N ATOM 2770 CG LEU B 311 95.934 -37.814 -12.484 1.00 56.98 c ANISOU 2725 N GLN I i 306 10552 11013 6045 -1619 638 -551 N ANISOU 2770 CG LEU B 311 7425 6994 7229 634 -433 803 c ATOM 2726 CA GLN I 3 306 96.682 -41.627 -23.480 1.00 83.69 c ATOM 2771 CD1 LEU B 311 96.606 -36.453 -12.360 1.00 47.40 c ANISOU 2726 CA GLN B 306 11693 13286 6819 -1910 305 -524 c ANISOU 2771 CD1 LEU B 311 6067 5651 6293 880 -383 984 c ATOM 2727 CB GLN I i 306 96.770 -41.348 -24.983 1.00 89.69 c ATOM 2772 CD2 LEU B 311 96.744 -38.908 -11.794 1.00 51.52 c ANISOU 2727 CB GLN B 306 12464 14757 6855 -2139 304 -473 c ANISOU 2772 CD2 LEU B 311 6948 6007 6620 636 -301 571 c ATOM 2728 CG GLN I 3 306 97.738 -40.222 -25.362 1.00 88.91 c ATOM 2773 C LEU B 311 92.644 -38.874 -10.800 1.00 42.01 c ANISOU 2728 CG GLN B 306 12414 14492 6877 -1680 370 50 c ANISOU 2773 C LEU B 311 5342 5329 5290 334 -630 684 c ATOM 2729 CD GLN I 3 306 97.183 -38.826 -25.134 1.00 87.21 c ATOM 2774 O LEU B 311 91.672 -38.280 -11.253 1.0044.08 o ANISOU 2729 CD GLN : B 306 11843 14560 6733 -1200 16 783 c ANISOU 2774 O LEU B 311 5364 5894 5492 291 -762 867 o ATOM 2730 OE1 GLN I B 306 96.444 -38.299 -25.970 1.00 75.15 o ATOM 2775 N ILE B 312 92.693 -39.347 -9.566 1.00 41.91 ■f ANISOU 2730 OE1 GLN B 306 10070 13869 4616 -1234 -230 1135 o ANISOU 2775 N ILE B 312 5441 5048 5435 400 -542 572 N ATOM 2731 NE2 GLN I Ϊ 306 97.551 -38.211 -24.006 1.00 63.98 N ATOM 2776 CA ILE B 312 91.583 -39.157 -8.662 1.00 36.06 c ANISOU 2731 NE2 GLN B 306 8850 10943 4515 -751 26 1029 N ANISOU 2776 CA ILE B 312 4577 4309 4816 401 -574 611 c ATOM 2732 C GLN I i 306 95.820 -42.851 -23.191 1.00 96.38 C ATOM 2777 CB ILE B 312 91.105 -40.489 -8.120 1.00 47.47 c ANISOU 2732 C GLN B 306 13301 14974 8346 -2391 370 -1080 ANISOU 2777 CB ILE B 312 6186 5628 6222 247 -439 411 c ATOM 2733 O GLN I i 306 96.202 -43.983 -23.496 1.00 97.12 C ATOM 2778 CGI ILE B 312 90.933 -41.467 -9.271 1.0045.65 c ANISOU 2733 O GLN B 306 13657 14822 8423 -2794 788 -1645 ANISOU 2778 CGI ILE B 312 6026 5543 5777 -52 -377 217 c ATOM 2734 N ASN I i 307 94.674 -42.600 -22.562 1.00 99.08 > ATOM 2779 CD1 ILE B 312 90.289 -42.752 -8.856 1.00 58.25 c ANISOU 2734 N ASN I B 307 13340 15588 8717 -2335 22 -914 ANISOU 2779 CD1 ILE B 312 7744 6983 7405 -259 -155 -14 c ATOM 2735 CA ASN I B 307 93.634 -43.602 -22.362 1.00 97.27 ATOM 2780 CG2 ILE B 312 89.792 -40.315 -7.375 1.0041.61 c ANISOU 2735 CA ASN B 307 13023 15569 8368 -2807 37 -1399 ANISOU 2780 CG2 ILE B 312 5296 4919 5596 203 -456 445 c ATOM 2736 CB ASN I i 307 93.266 -44.260 -23.695 1.00115.55 ATOM 2781 C ILE B 312 c ANISOU 2736 CB ASN B 307 15329 18632 9942 -3472 120 -1900 ANISOU 2781 C ILE B 312 4329 3923 4850 635 -546 683 c ATOM 2737 CG ASN I i 307 91.855 -43.956 -24.121 1.00132.77 ATOM 2782 O ILE B 312 92.630 -38.660 -6.567 1.00 45.48 o ANISOU 2737 CG ASN ] B 307 17004 21635 11807 -3595 -313 -1726 ANISOU 2782 O ILE B 312 5870 5142 6268 727 -469 582 o ATOM 2738 OD1 ASN I B 307 91.103 -44.855 -24.503 1.00138.43 ATOM 2783 N ALA B 313 91.651 -36.964 -7.662 1.00 35.57 N ANISOU 2738 OD1 ASN B 307 17574 22601 12423 -4070 -202 -2189 ANISOU 2783 N ALA B 313 4234 4124 5156 727 -576 864 N ATOM 2739 ND2 ASN I i 307 91.476 -42.688 -24.043 1.00135.98 N ATOM 2784 CA ALA B 313 91.977 -35.984 -6.637 1.0044.62 c ANISOU 2739 ND2 ASN B 307 17112 22420 12135 -3143 -745 -1026 N ANISOU 2784 CA ALA B 313 5308 5090 6557 875 -474 849 c ATOM 2740 C ASN I 3 307 93.951 -44.681 -21.330 1.00 83.66 ATOM 2785 CB ALA B 313 92.466 -34.698 -7.260 1.00 34.12 c ANISOU 2740 C ASN B 307 11549 12992 7248 -2847 443 -1779 ANISOU 2785 CB ALA B 313 3804 3732 5430 997 -401 1007 c ATOM 2741 O ASN I 3 307 93.215 -45.659 -21.211 1.00 79.29 o ATOM 2786 C ALA B 313 90.766 -35.716 -5.764 1.00 44.06 c ANISOU 2741 O ASN B 307 10976 12485 6664 -3279 606 -2257 o ANISOU 2786 C ALA B 313 5121 4981 6640 844 -410 871 c ATOM 2742 N ASN I 3 308 95.028 -44.517 -20.575 1.00 59.59 N ATOM 2787 O ALA B 313 89.652 -35.593 -6.257 1.00 46.95 o ANISOU 2742 N ASN I B 308 8701 9188 4752 -2398 628 -1554 N ANISOU 2787 O ALA B 313 5307 5481 7049 787 -451 1041 o ATOM 2743 CA ASN I B 308 95.424 -45.586 -19.670 1.00 61.32 C ATOM 2788 N TYR B 314 90.991 -35.614 -4.462 1.00 45.87 N ANISOU 2743 CA ASN B 308 9141 8651 5506 -2392 1052 -1826 C ANISOU 2788 N TYR B 314 5427 5070 6933 876 -308 701 N ATOM 2744 CB ASN I i 308 96.572 -46.370 -20.276 1.00 66.55 C ATOM 2789 CA TYR B 314 89.894 -35.391 -3.540 1.00 48.33 c ANISOU 2744 CB ASN B 308 10125 8895 6266 -2559 1594 -2145 C ANISOU 2789 CA TYR B 314 5664 5310 7389 833 -192 684 c ATOM 2745 CG ASN I i 308 97.788 -45.508 -20.503 1.00 77.08 C ATOM 2790 CB TYR B 314 89.212 -36.709 -3.187 1.00 35.91 c ANISOU 2745 CG ASN ] B 308 11531 10048 7706 -2149 1549 -1767 C ANISOU 2790 CB TYR B 314 4252 3762 5629 735 -224 631 c ATOM 2746 OD1 ASN I B 308 97.709 -44.283 -20.426 1.00 76.57 O ATOM 2791 CG TYR B 314 90.161 -37.760 -2.650 1.00 34.89 c ANISOU 2746 OD1 ASN B 308 11276 10264 7554 -1815 1127 -1312 O ANISOU 2791 CG TYR B 314 4393 3612 5251 776 -232 506 c ATOM 2747 ND2 ASN I i 308 98.924 -46.139 -20.787 1.00 80.65 N ATOM 2792 CD1 TYR B 314 90.884 -38.577 -3.516 1.00 30.60 c ANISOU 2747 ND2 ASN B 308 12242 9994 8407 -2173 2043 -1955 N ANISOU 2792 CD1 TYR B 314 3970 3101 4556 770 -303 514 c ATOM 2748 C ASN I 3 308 95.816 -45.139 -18.269 1.00 66.14 C ATOM 2793 CE1 TYR B 314 91.753 -39.529 -3.040 1.00 34.50 c ANISOU 2748 C ASN B 308 9729 8722 6679 -1823 950 -1412 C ANISOU 2793 CE1 TYR B 314 4669 3542 4899 857 -251 479 c ATOM 2749 O ASN I 3 308 96.478 -45.877 -17.540 1.00 66.00 O ATOM 2794 CZ TYR B 314 91.902 -39.692 -1.673 1.00 48.14 c ANISOU 2749 O ASN B 308 9892 8079 7105 -1681 1302 -1481 O ANISOU 2794 CZ TYR B 314 6473 5270 6546 963 -178 469 c ATOM 2750 N CYS I 3 309 95.414 -43.937 -17.889 1.00 57.64 N ATOM 2795 OH TYR B 314 92.762 -40.652 -1.190 1.00 52.05 o ANISOU 2750 N CYS I B 309 8409 7910 5581 -1500 504 -975 N ANISOU 2795 OH TYR B 314 7125 5765 6889 1110 -117 543 o ATOM 2751 CA CYS I B 309 95.788 -43.419 -16.590 1.00 54.76 C ATOM 2796 CE2 TYR B 314 91.197 -38.895 -0.786 1.00 36.52 c ANISOU 2751 CA CYS B 309 8006 7120 5682 -1022 410 -648 C ANISOU 2796 CE2 TYR B 314 4910 3822 5143 932 -134 414 c ATOM 2752 CB CYS I i 309 97.161 -42.763 -16.660 1.0048.32 C ATOM 2797 CD2 TYR B 314 90.331 -37.934 -1.278 1.00 33.36 c ANISOU 2752 CB CYS B 309 7269 6026 5065 -681 469 -420 C ANISOU 2797 CD2 TYR B 314 4315 3387 4972 832 -135 414 c ATOM 2753 SG CYS I i 309 97.792 -42.250 -15.068 1.00 71.58 S ATOM 2798 C TYR B 314 90.355 -34.690 -2.273 1.00 48.00 c ANISOU 2753 SG CYS B 309 10146 8523 8527 -182 390 -139 S ANISOU 2798 C TYR B 314 5634 5157 7445 859 -28 481 c ATOM 2754 C CYS I i 309 94.754 -42.419 -16.107 1.00 64.21 C ATOM 2799 O TYR B 314 91.491 -34.849 -1.823 1.00 42.97 o ANISOU 2754 C CYS B 309 8904 8648 6844 -861 6 -337 C ANISOU 2799 O TYR B 314 5108 4574 6644 890 -66 316 o ATOM 2755 O CYS ] 3 309 94.331 -41.543 -16.856 1.00 73.26 O ATOM 2800 N GLN B 315 89.448 -33.912 -1.705 1.00 59.28 N ANISOU 2755 O CYS ] B 309 9852 10282 7702 -862 -242 -112 O ANISOU 2800 N GLN B 315 5285 7275 9962 -655 546 -2539 N ATOM 2756 N ARG I B 310 94.348 -42.544 -14.850 1.00 50.79 N ATOM 2801 CA GLN B 315 89.703 -33.222 -0.460 1.00 57.58 c ANISOU 2756 N ARG i 310 7165 6683 5451 -702 -20 -285 N ANISOU 2801 CA GLN B 315 5768 6696 9414 -642 589 -2977 c ATOM 2757 CA ARG i 310 93.315 -41.663 -14.343 1.00 40.48 C ATOM 2802 CB GLN B 315 89.345 -31.750 -0.599 1.00 61.20 ANISOU 2802 CB GLN B 315 6516 6556 10180 -785 1109 -2953 C ANISOU 2847 CA SERB 321 16410 14104 11889 624 1371 -2209 ATOM 2803 CG GLN B 315 90.256 -30.815 0.155 1.00 89.53 C ATOM 2848 CB SER B 321 85.016 -38.864 8.981 1.00105.77 ANISOU 2803 CG GLN B 315 10610 9882 13524 -1154 1002 -3613 C ANISOU 2848 CB SER B 321 16063 13693 10433 296 550 -2265 ATOM 2804 CD GLN B 315 90.389 -29.473 -0.536 1.00 94.49 C ATOM 2849 OG SER B 321 85.343 -38.091 10.112 1.00109.17 ANISOU 2804 CD GLN B 315 11252 10043 14608 -1511 1279 -3599 C ANISOU 2849 OG SER B 321 17093 14123 10263 -135 660 -2816 ATOM 2805 OE1 GLN B 315 89.766 -29.230 -1.572 1.00 97.90 O ATOM 2850 C SER B 321 83.123 -38.891 7.380 1.00106.37 ANISOU 2805 OE1 GLN B 315 11292 10353 15555 -1464 1525 -3023 O ANISOU 2850 C SER B 321 15449 13590 11376 932 1622 -1574 ATOM 2806 NE2 GLN B 315 91.210 -28.594 0.031 1.00 97.65 N ATOM 2851 O SER B 321 83.075 -40.098 7.608 1.00105.37 ANISOU 2806 NE2 GLN B 315 12113 10192 14799 -1936 1211 -4193 N ANISOU 2851 O SER B 321 15389 13738 10908 901 1142 -1224 ATOM 2807 C GLN B 315 88.831 -33.875 0.595 1.00 58.08 C ATOM 2852 N SER B 322 82.225 -38.274 6.627 1.00103.49 ANISOU 2807 C GLN B 315 6297 6678 9091 -204 767 -2828 C ANISOU 2852 N SER B 322 14748 13040 11533 1200 2347 -1381 ATOM 2808 O GLN B 315 87.622 -33.983 0.429 1.00 71.31 O ATOM 2853 CA SER B 322 81.231 -39.056 5.919 1.00 99.85 ANISOU 2808 O GLN B 315 7977 8210 10908 106 1248 -2339 O ANISOU 2853 CA SERB 322 13897 12801 11240 1418 2544 -737 C ATOM 2809 N GLU B 316 89.452 -34.321 1.676 1.00 90.11 N ATOM 2854 CB SER B 322 79.954 -38.249 5.711 1.00102.64 C ANISOU 2809 N GLU I 5316 10714 10894 12631 -233 349 -3212 N ANISOU 2854 CB SER B 322 14086 13017 11895 1678 3486 -554 C ATOM 2810 CA GLU I Ϊ 316 88.724 -35.019 2.722 1.00 93.60 C ATOM 2855 OG SER B 322 78.853 -39.113 5.499 1.00104.22 O ANISOU 2810 CA GLU B 316 11616 11348 12600 61 428 -3070 C ANISOU 2855 OG SER B 322 14091 13580 11927 1775 3694 31 O ATOM 2811 CB GLU I i 316 89.582 -36.144 3.300 1.00105.57 C ATOM 2856 C SER B 322 81.823 -39.476 4.580 1.00 91.47 C ANISOU 2811 CB GLU B 316 13094 13285 13734 35 -356 -3200 C ANISOU 2856 C SER B 322 12193 11796 10763 1452 2113 -479 ATOM 2812 CG GLU I Ϊ 316 88.816 -37.169 4.111 1.00115.39 C ATOM 2857 O SER B 322 81.146 -40.059 3.734 1.00 78.84 ANISOU 2812 CG GLU B 316 14680 14624 14540 304 -397 -2875 C ANISOU 2857 O SER B 322 10176 10394 9386 1540 2248 o ATOM 2813 CD GLU I Ϊ 316 89.676 -38.361 4.501 1.00119.83 C ATOM 2858 N PHE B 323 83.102 -39.175 4.400 1.00 56.42 N ANISOU 2813 CD GLU B 316 15103 15530 14896 326 -1247 -2859 C ANISOU 2858 N PHE B 323 7669 7241 6528 1311 1614 -874 N ATOM 2814 OE1 GLU : B 316 90.445 -38.849 3.644 1.00119.94 O ATOM 2859 CA PHE B 323 83.759 -39.411 3.132 1.00 54.89 C ANISOU 2814 OE1 GLU B 316 14482 15730 15359 359 -1653 -2888 O ANISOU 2859 CA PHE B 323 6840 7121 6896 1274 1283 -775 c ATOM 2815 OE2 GLU B 316 89.586 -38.803 5.665 1.00118.84 O ATOM 2860 CB PHE B 323 85.122 -38.729 3.103 1.00 53.29 c ANISOU 2815 OE2 GLU B 316 15485 15488 14180 292 -1505 -2812 O ANISOU 2860 CB PHE B 323 6582 6790 6875 1079 880 -1320 c ATOM 2816 C GLU B 316 88.316 -34.033 3.806 1.00 92.26 C ATOM 2861 CG PHE Ϊ 323 85.891 -38.992 1.852 1.00 53.28 c ANISOU 2816 C GLU B 316 12193 10764 12099 -12 922 -3393 C ANISOU 2861 CG PHE ] B 323 5908 6939 7396 972 542 -1317 c ATOM 2817 O GLU I 3 316 89.149 -33.275 4.305 1.00 95.73 O ATOM 2862 CD1 PHE I B 323 85.511 -38.400 0.658 1.0046.58 c ANISOU 2817 O GLU B 316 12943 11098 12331 -384 785 -3923 O ANISOU 2862 CD1 PHE i 323 4572 6071 7056 903 942 -1079 c ATOM 2818 N PRO I i 317 87.021 -34.024 4.163 1.00 95.43 N ATOM 2863 CE1 PHE B 323 86.217 -38.641 -0.507 1.00 46.77 c ANISOU 2818 N PRO I B 317 12868 10949 12444 303 1546 -3115 N ANISOU 2863 CE1 PHE B 323 3975 6317 7480 683 671 -1124 c ATOM 2819 CA PRO I B 317 86.580 -33.105 5.211 1.00102.12 C ATOM 2864 CZ PHE B 323 87.323 -39.484 -0.482 1.0045.64 c ANISOU 2819 CA PRO i 317 14411 11385 13003 237 2132 -3519 C ANISOU 2864 CZ PHE B 323 3650 6366 7323 625 37 -1463 c ATOM 2820 CB PRO B 317 85.055 -33.279 5.225 1.00 99.20 C ATOM 2865 CE2 PHE B 323 87.711 -40.087 0.712 1.00 50.47 c ANISOU 2820 CB PRO B 317 14039 10885 12767 684 2829 -3068 C ANISOU 2865 CE2 PHE B 323 4710 6940 7528 789 -405 -1640 c ATOM 2821 CG PRO I i 317 84.721 -34.108 4.012 1.00 92.31 C ATOM 2866 CD2 PHE B 323 86.993 -39.838 1.868 1.00 53.46 c ANISOU 2821 CG PRO B 317 12445 10318 12312 918 2615 -2382 C ANISOU 2866 CD2 PHE B 323 5749 7147 7415 913 -174 -1539 c ATOM 2822 CD PRO I i 317 85.937 -34.918 3.727 1.00 85.93 C ATOM 2867 C PHE B 323 83.915 -40.894 2.864 1.00 51.27 c ANISOU 2822 CD PRO B 317 11366 9927 11358 677 1744 -2484 C ANISOU 2867 C PHE B 323 6207 6926 6347 1281 773 -500 c ATOM 2823 C PRO i 317 87.150 -33.588 6.527 1.00112.78 C ATOM 2868 O PHE B 323 84.216 -41.676 3.762 1.00 61.61 o ANISOU 2823 C PRO B 317 16298 13054 13501 -68 1692 -3909 C ANISOU 2868 O PHE B 323 7906 8292 7210 1268 310 -543 o ATOM 2824 O PRO B 317 87.177 -34.796 6.753 1.00114.74 O ATOM 2869 N SER B 324 83.697 -41.270 1.611 1.00 52.95 N ANISOU 2824 O PRO B 317 16441 13739 13415 19 1188 -3608 O ANISOU 2869 N SER B 324 5844 7283 6991 1256 867 -200 N ATOM 2825 N ALA i 318 87.605 -32.676 7.376 1.00120.72 N ATOM 2870 CA SER B 324 83.920 -42.637 1.171 1.00 53.22 c ANISOU 2825 N ALA I B 318 17879 13842 14148 -472 1859 -4539 N ANISOU 2870 CA SERB 324 5667 7485 7068 1227 457 -34 c ATOM 2826 CA ALA B] 318 88.154 -33.069 8.668 1.00131.67 C ATOM 2871 CB SER B 324 82.621 -43.275 0.704 1.00 50.70 c ANISOU 2826 CA ALA i 318 19789 15612 14629 -899 1418 -4878 C ANISOU 2871 CB SER B 324 5251 7371 6642 1206 884 544 c ATOM 2827 CB ALA B 318 89.649 -32.802 8.714 1.00129.55 C ATOM 2872 OG SER B 324 82.895 -44.471 0.002 1.00 62.56 o ANISOU 2827 CB ALA B 318 19451 15578 14193 -1403 706 -5258 C ANISOU 2872 OG SER B 324 6478 8981 8311 1095 583 628 o ATOM 2828 C ALA B 318 87.443 -32.358 9.818 1.00147.32 C ATOM 2873 C SER B 324 84.932 -42.650 0.035 1.00 51.81 c ANISOU 2828 C ALA B 318 22552 17316 16106 -1116 2192 -5357 C ANISOU 2873 C SER B 324 4862 7378 7445 1074 191 -307 c ATOM 2829 O ALA ] i 318 87.590 -31.149 9.986 1.00150.36 O ATOM 2874 O SER B 324 84.710 -42.049 -1.012 1.0043.28 o ANISOU 2829 O ALA B 318 23290 17228 16610 -1373 2705 -5914 O ANISOU 2874 O SER B 324 3325 6410 6711 899 546 -200 o ATOM 2830 N ASP 5319 86.682 -33.106 10.616 1.00158.28 N ATOM 2875 N LEU B 325 86.043 -43.344 0.246 1.00 53.65 N ANISOU 2830 N ASP I B 319 24226 18992 16920 -1063 2301 -5177 N ANISOU 2875 N LEU B 325 7977 5221 7187 -189 1536 -759 N ATOM 2831 CA ASP B ] 319 86.553 -34.551 10.455 1.00162.22 C ATOM 2876 CA LEU B 325 87.075 -43.425 -0.771 1.00 45.96 c ANISOU 2831 CA ASP i 319 24382 19987 17266 -818 1656 -4513 C ANISOU 2876 CA LEU B 325 6870 4368 6224 -331 1251 -585 c ATOM 2832 CB ASP B 319 87.586 -35.275 11.330 1.00167.60 C ATOM 2877 CB LEU B 325 88.379 -43.974 -0.196 1.00 51.17 c ANISOU 2832 CB ASP B 319 25290 21220 17169 -1309 682 -4556 C ANISOU 2877 CB LEU B 325 7750 4907 6786 -598 1099 -572 c ATOM 2833 CG ASP B 319 87.745 -36.739 10.961 1.00164.73 C ATOM 2878 CG LEU B 325 89.561 -43.890 -1.160 1.00 48.90 c ANISOU 2833 CG ASP B 319 24478 21224 16889 -1011 -124 -3867 C ANISOU 2878 CG LEU B 325 7319 4692 6568 -733 869 -390 c ATOM 2834 OD1 ASP B 319 87.355 -37.604 11.773 1.00169.02 O ATOM 2879 CD1 LEU B 325 89.785 -42.442 -1.565 1.00 39.94 c ANISOU 2834 OD1 ASP B 319 25222 21942 17057 -909 -64 -3482 O ANISOU 2879 CD1 LEU B 325 6311 3392 5471 -654 731 -224 c ATOM 2835 OD2 ASP B 319 88.263 -37.028 9.861 1.00157.65 O ATOM 2880 CD2 LEU B 325 90.810 -44.455 -0.521 1.00 54.14 c ANISOU 2835 OD2 ASP B 319 23029 20427 16444 -900 -793 -3738 O ANISOU 2880 CD2 LEU B 325 8125 5189 7258 -980 705 -366 c ATOM 2836 C ASP B 319 85.144 -35.029 10.811 1.00166.37 C ATOM 2881 C LEU B 325 86.616 -44.297 -1.938 1.00 42.53 c ANISOU 2836 C ASP B 319 25075 20562 17578 -540 2251 -4203 C ANISOU 2881 C LEU B 325 5996 4310 5853 -332 1245 -549 c ATOM 2837 O ASP B 319 84.951 -35.697 11.826 1.00171.36 O ATOM 2882 O LEU B 325 86.960 -44.042 -3.090 1.00 44.88 o ANISOU 2837 O ASP B 319 26132 21587 17391 -830 2045 -4163 O ANISOU 2882 O LEU B 325 6146 4738 6168 -357 1085 -403 o ATOM 2838 N ASP ] Ϊ 320 84.157 -34.672 9.991 1.00162.47 N ATOM 2883 N SER B 326 85.851 -45.339 -1.637 1.00 38.02 N ANISOU 2838 N ASP I B 320 24229 19716 17786 -35 2971 -3951 N ANISOU 2883 N SER B 326 5260 3899 5288 -337 1408 -674 N ATOM 2839 CA ASP ] B 320 82.827 -35.260 10.122 1.00158.27 C ATOM 2884 CA SER B 326 85.358 -46.219 -2.687 1.00 41.93 c ANISOU 2839 CA ASP i 320 23664 19337 17132 269 3459 -3536 C ANISOU 2884 CA SERB 326 5390 4711 5830 -355 1362 -646 c ATOM 2840 CB ASP B 320 81.783 -34.451 9.346 1.00157.98 C ATOM 2885 CB SER B 326 84.818 -47.528 -2.113 1.00 39.92 c ANISOU 2840 CB ASP B 320 23262 18840 17923 773 4387 -3386 C ANISOU 2885 CB SER B 326 5026 4582 5561 -440 1495 -779 c ATOM 2841 CG ASP B 320 80.381 -34.580 9.933 1.00160.12 C ATOM 2886 OG SERB 326 83.830 -47.272 -1.143 1.00 57.38 o ANISOU 2841 CG ASP B 320 23687 19221 17932 960 5184 -3297 C ANISOU 2886 OG SER B 326 7277 6688 7838 -320 1751 -864 o ATOM 2842 OD1 ASP B 320 79.741 -35.636 9.744 1.00157.27 O ATOM 2887 C SER B 326 84.293 -45.533 -3.554 1.00 48.03 c ANISOU 2842 OD1 ASP B 320 23082 19295 17379 1102 5014 -2702 O ANISOU 2887 C SER B 326 5924 5558 6767 -161 1318 -539 c ATOM 2843 OD2 ASP B 320 79.918 -33.612 10.575 1.00161.79 O ATOM 2888 O SER B 326 84.179 -45.823 -4.741 1.00 53.17 o ANISOU 2843 OD2 ASP B 320 24047 19168 18259 907 5697 -3668 O ANISOU 2888 O SER B 326 6384 6408 7409 -208 1151 -439 o ATOM 2844 C ASP B 320 82.956 -36.662 9.546 1.00145.06 C ATOM 2889 N GLN B 327 83.509 -44.634 -2.962 1.00 34.97 N ANISOU 2844 C ASP B 320 21570 18082 15464 424 2691 -2844 C ANISOU 2889 N GLN I Ϊ 327 4301 3713 5274 50 1456 -563 N ATOM 2845 O ASP B 320 82.335 -37.614 10.021 1.00147.51 O ATOM 2890 CA GLN I Ϊ 327 82.537 -43.864 -3.736 1.00 50.89 c ANISOU 2845 O ASP B 320 22039 18743 15265 402 2602 -2500 O ANISOU 2890 CA GLN B 327 6070 5721 7544 250 1355 -438 ATOM 2846 N SER B 321 83.802 -36.765 8.523 1.00128.64 N ATOM 2891 CB GLN I i 327 81.669 -42.983 -2.840 1.00 43.63 ANISOU 2846 N SER B 321 18971 15947 13961 530 2157 -2690 N ANISOU 2891 CB GLN B 327 5167 4543 6868 519 1599 -530 ATOM 2847 CA SER B 321 84.242 -38.039 7.953 1.00111.60 C ATOM 2892 CG GLN I Ϊ 327 80.448 -43.685 -2.277 1.00 69.58 ANISOU 2892 CG GLN : ! 327 8154 7920 10361 615 1908 -644 ANISOU 2930 NH2 ARG B 331 12254 10127 12798 -754 1136 N ATOM 2893 CD GLN I 327 79.598 -44.342 -3.357 1.00 76.84 ATOM 2931 C ARG B 331 83.488 -42.005 -10.946 1.00 61.47 C ANISOU 2893 CD GLN : ! 327 8607 9088 11501 598 1706 -496 ANISOU 2931 C ARG B 331 7509 7510 8338 -393 -287 695 C ATOM 2894 OE1 GLN I 327 78.858 -43.669 -4.080 1.00 87.42 O ATOM 2932 O ARG B 331 82.986 -41.671 -12.019 1.00 62.26 O ANISOU 2894 OE1 GLN i 327 9685 10364 13167 762 1523 -348 O c ANISOU 2932 O ARG B 331 7631 7614 8410 -486 -621 908 O ATOM 2895 NE2 GLN I 327 79.707 -45.662 -3.475 1.00 71.13 N ATOM 2933 N HIS B 332 84.771 -42.292 -10.848 1.00 59.85 N ANISOU 2895 NE2 GLN i 327 7800 8612 10614 383 1686 -522 N ANISOU 2933 N HIS B 332 7487 7383 7868 -544 -86 619 N ATOM 2896 C GLN 327 83.261 -42.983 -4.738 1.00 57.49 C ATOM 2934 CA HIS B 332 85.656 -42.259 -11.992 1.00 56.95 C ANISOU 2896 C GLN B ! 327 7021 6512 8312 204 1051 -247 c ANISOU 2934 CA HIS B 332 7331 7158 7150 -822 -152 755 C ATOM 2897 O GLN B 327 82.832 -42.802 -5.879 1.00 56.04 o ATOM 2935 CB HIS B 332 87.080 -42.058 -11.532 1.00 50.51 C ANISOU 2897 O GLN B i 327 6653 6431 8207 207 817 -82 o ANISOU 2935 CB HIS B 332 6645 6305 6242 -915 65 723 C ATOM 2898 N GLU B 328 84.377 -42.432 -4.290 1.00 55.93 N ATOM 2936 CG HIS B 332 87.377 -40.661 -11.139 1.00 56.42 C ANISOU 2898 N GLU B i 328 7153 6138 7960 125 1028 -247 N ANISOU 2936 CG HIS B 332 7528 6783 7126 -857 -86 900 C ATOM 2899 CA GLU I i 328 85.125 -41.490 -5.098 1.00 58.25 c ATOM 2937 NDl HIS B 332 88.018 -39.781 -11.969 1.00 64.51 N ANISOU 2899 CA GLU : B 328 7578 6357 8196 57 768 -46 c ANISOU 2937 NDl HIS B 332 8741 7788 7983 -1057 -253 1159 N ATOM 2900 CB GLU B i 328 86.137 -40.743 -4.237 1.00 43.81 c ATOM 2938 CE1 HIS B 332 88.131 -38.619 -11.364 1.00 60.89 C ANISOU 2900 CB GLU ] B 328 6118 4238 6289 13 758 -56 c ANISOU 2938 CE1 HIS B 332 8384 7036 7716 -956 -407 1277 C ATOM 2901 CG GLU I i 328 86.706 -39.521 -4.912 1.00 51.35 c ATOM 2939 NE2 HIS B 332 87.571 -38.711 -10.179 1.00 54.89 N ANISOU 2901 CG GLU : B 328 7214 5045 7251 -23 485 173 c ANISOU 2939 NE2 HIS B 332 7537 6105 7214 -689 -312 1078 N ATOM 2902 CD GLU I i 328 85.628 -38.562 -5.416 1.00 69.56 c ATOM 2940 CD2 HIS B 332 87.093 -39.977 -10.014 1.00 53.58 C ANISOU 2902 CD GLU : B 328 9415 7232 9784 202 343 271 c ANISOU 2940 CD2 HIS B 332 7181 6142 7036 -634 -100 852 C ATOM 2903 OE1 GLU I B 328 85.900 -37.848 -6.403 1.00 69.95 o ATOM 2941 C HIS B 332 85.592 -43.535 -12.801 1.00 69.45 C ANISOU 2903 OE1 GLU ! 328 9487 7273 9817 116 61 509 o ANISOU 2941 C HIS B 332 8909 9014 8467 -995 -102 660 C ATOM 2904 OE2 GLU I 328 84.517 -38.516 -4.831 1.00 78.20 o ATOM 2942 O HIS B 332 85.662 -43.518 -13.998 1.00 66.53 O ANISOU 2904 OE2 GLU ! 328 10392 8224 11096 452 512 123 o ANISOU 2942 O HIS B 332 8718 8747 7813 -1206 -267 804 O ATOM 2905 C GLU I 328 85.818 -42.176 -6.272 1.00 57.13 c ATOM 2943 N LEU B 333 85.440 -44.654 -12.133 1.00 74.71 N ANISOU 2905 C GLU ! 328 7349 6499 7861 -181 640 63 c ANISOU 2943 N LEU B 333 9419 9769 9200 -926 114 416 N ATOM 2906 O GLU I 328 85.968 -41.603 -7.350 1.00 52.82 o ATOM 2944 CA LEU B 333 85.391 -45.904 -12.828 1.00 79.69 C ANISOU 2906 O GLU i 328 6810 5999 7261 -251 431 258 o ANISOU 2944 CA LEU B 333 10062 10617 9600 -1071 162 287 C ATOM 2907 N VAL I 329 86.240 -43.411 -6.051 1.00 35.43 N ATOM 2945 CB LEU B 333 85.286 -47.035 -11.851 1.00 75.72 C ANISOU 2907 N VAL B i 329 4545 3919 4997 -315 775 -73 N ANISOU 2945 CB LEU B 333 9371 10149 9249 -973 360 37 C ATOM 2908 CA VAL B i 329 86.878 -44.178 -7.101 1.00 41.84 c ATOM 2946 CG LEU B 333 86.653 -47.644 -11.683 1.00 91.95 C ANISOU 2908 CA VAL ] B 329 5282 4981 5636 -513 731 -34 c ANISOU 2946 CG LEU B 333 11497 12286 11153 -1090 628 -138 C ATOM 2909 CB VAL B i 329 87.690 -45.347 -6.522 1.00 44.73 c ATOM 2947 CD1 LEU I 333 87.063 -47.539 -10.262 1.00106.42 C ANISOU 2909 CB VAL I B 329 5643 5401 5952 -642 874 -201 c ANISOU 2947 CD1 LEU 1 333 13228 13977 13230 -977 781 -253 C ATOM 2910 CGI VAL I B 329 88.324 -46.150 -7.623 1.00 38.21 c ATOM 2948 CD2 LEU I 333 86.593 -49.084 -12.110 1.00 77.02 C ANISOU 2910 CGI VAL ! 329 4732 4807 4981 -808 889 -207 c ANISOU 2948 CD2 LEU 1 333 9611 10560 9093 -1189 653 -312 C ATOM 2911 CG2 VAL I 329 88.767 -44.813 -5.595 1.00 40.56 c ATOM 2949 C LEU 333 84.217 -45.910 -13.758 1.00 91.96 C ANISOU 2911 CG2 VAL ! 329 5322 4618 5472 -698 873 -183 c ANISOU 2949 C LEU B 333 11627 12212 11102 -1132 -180 428 C ATOM 2912 C VAL I 329 85.817 -44.677 -8.076 1.00 47.35 c ATOM 2950 O LEU B 333 84.230 -46.563 -14.770 1.00105.03 O ANISOU 2912 C VAL i 329 5785 5888 6318 -496 636 -3 c ANISOU 2950 O LEU B 333 13499 14002 12407 -1352 -264 449 O ATOM 2913 O VAL I 329 86.004 -44.648 -9.293 1.00 43.12 o ATOM 2951 N ARG B 334 83.186 -45.174 -13.423 1.00 91.31 N ANISOU 2913 O VAL S 329 5278 5492 5614 -628 505 119 o ANISOU 2951 N ARG B 334 11320 11988 11387 -942 -378 525 N ATOM 2914 N LEU I 330 84.689 -45.119 -7.531 1.00 47.31 N ATOM 2952 CA ARG B 334 82.035 -45.205 -14.260 1.00 89.10 C ANISOU 2914 N LEU B ! 330 5603 5888 6484 -359 696 -97 N ANISOU 2952 CA ARG B 334 11001 11676 11178 -997 -796 727 C ATOM 2915 CA LEU E i 330 83.591 -45.603 -8.359 1.00 51.28 c ATOM 2953 CB ARG B 334 80.808 -44.804 -13.468 1.00 75.67 C ANISOU 2915 CA LEU ] B 330 5892 6545 7046 -351 545 -36 c ANISOU 2953 CB ARG B 334 8925 9791 10033 -724 -913 796 C ATOM 2916 CB LEU B i 330 82.451 -46.156 -7.501 1.00 46.75 c ATOM 2954 CG ARG I 3 334 80.254 -45.999 -12.721 1.00 73.29 C ANISOU 2916 CB LEU ] B 330 5074 5962 6725 -212 680 -143 c ANISOU 2954 CG ARG B 334 8330 9579 9938 -647 -793 638 C ATOM 2917 CG LEU E i 330 82.684 -47.558 -6.942 1.00 54.79 c ATOM 2955 CD ARG I 3 334 79.775 -45.703 -11.333 1.00 64.53 C ANISOU 2917 CG LEU ] B 330 6064 7114 7639 -332 840 -329 c ANISOU 2955 CD ARG B 334 6946 8354 9219 -368 -474 508 C ATOM 2918 CD1 LEU ] B 330 81.655 -47.889 -5.881 1.00 51.25 c ATOM 2956 NE ARG I 3 334 79.520 -46.958 -10.654 1.00 72.05 N ANISOU 2918 CD1 LEU 1 330 5424 6622 7424 -216 1039 -415 c ANISOU 2956 NE ARG B 334 7705 9435 10237 -369 -271 330 N ATOM 2919 CD2 LEU I 330 82.636 -48.579 -8.064 1.00 53.00 c ATOM 2957 CZ ARG I i 334 78.933 -47.079 -9.476 1.00 76.05 C ANISOU 2919 CD2 LEU 1 330 5779 7105 7255 -500 656 -314 c ANISOU 2957 CZ ARG B 334 7962 9875 11057 -184 16 218 C ATOM 2920 C LEU 330 83.068 -44.524 -9.307 1.00 54.99 ATOM 2958 NHl ARG B 334 78.533 -46.021 -8.821 1.00 78.83 N

ANISOU 2920 C LEU B 330 6359 6940 7595 -308 259 201 c ANISOU 2958 NHl ARG B 334 8239 10021 11691 50 164 232 N ATOM 2921 O LEU B 330 82.610 -44.819 -10.408 1.00 57.84 o ATOM 2959 NH2 ARG B 334 78.743 -48.268 -8.957 1.00 66.41 N ANISOU 2921 O LEU B 330 6677 7423 7876 -419 19 321 o ANISOU 2959 NH2 ARG B 334 6600 8781 9851 -245 164 88 N ATOM 2922 N ARG B 331 83.141 -43.272 -8.873 1.0044.63 N ATOM 2960 C ARG B 334 82.300 -44.320 -15.442 1.00102.82 C ANISOU 2922 N ARG B 331 5135 5388 6434 -164 241 276 N ANISOU 2960 C ARG B 334 13047 13355 12666 -1186 -1072 985 C ATOM 2923 CA ARG B 331 82.640 -42.173 -9.685 1.00 51.18 c ATOM 2961 O ARG I 3 334 81.736 -43.262 -15.601 1.00101.63 O ANISOU 2923 CA ARG B 331 5965 6085 7395 -116 -81 517 c ANISOU 2961 O ARG B 334 12830 12996 12789 -1078 -1323 1191 O ATOM 2924 CB ARG B 331 82.627 -40.871 -8.892 1.00 58.29 c ATOM 2962 N GLN I i 335 83.197 -44.826 -16.277 1.00109.97 N ANISOU 2924 CB ARG B 331 6949 6662 8535 103 -54 533 c ANISOU 2962 N GLN B 335 14293 14431 13058 -1464 -976 950 N ATOM 2925 CG ARG B 331 81.979 -39.723 -9.635 1.00 73.21 c ATOM 2963 CA GLN B 335 83.550 -44.255 -17.567 1.00105.58 C ANISOU 2925 CG ARG B 331 8801 8353 10661 189 -428 780 c ANISOU 2963 CA GLN B 335 14147 13893 12077 -1772 -1207 1177 C ATOM 2926 CD ARG B 331 82.192 -38.401 -8.920 1.00 80.82 c ATOM 2964 CB GLN B 335 83.440 -42.745 -17.557 1.00 99.33 C ANISOU 2926 CD ARG B 331 9928 8966 11814 384 -423 785 c ANISOU 2964 CB GLN B 335 13413 12881 11446 -1761 -1520 1490 C ATOM 2927 NE ARG B 331 83.533 -37.869 -9.145 1.00 94.70 N ATOM 2965 CG GLN B 335 83.642 -42.144 -16.222 1.00101.26 C ANISOU 2927 NE ARG B 331 12034 10698 13251 172 -503 890 N ANISOU 2965 CG GLN B 335 13508 12996 11969 -1546 -1285 1463 C ATOM 2928 CZ ARG B 331 83.867 -36.590 -8.994 1.00103.81 c ATOM 2966 CD GLN B 335 82.815 -40.915 -16.039 1.00108.55 C ANISOU 2928 CZ ARG B 331 13398 11548 14497 234 -680 1009 c ANISOU 2966 CD GLN B 335 14225 13618 13401 -1305 -1639 1647 C ATOM 2929 NHl ARG B 331 82.956 -35.701 -8.618 1.00109.37 N ATOM 2967 OE1 GLN B 335 81.608 -40.988 -15.881 1.00108.52 O ANISOU 2929 NHl ARG B 331 14018 11930 15609 533 -782 1005 ANISOU 2967 OE1 GLN B 335 14011 13523 13697 -1202 -1942 1716 O ATOM 2930 NH2 ARG B 331 85.115 -36.200 -9.227 1.00 92.59 N ATOM 2968 NE2 GLN B 335 83.455 -39.764 -16.085 1.00110.71 N ANISOU 2968 NE2 GLN B 335 14547 13709 13810 -1216 -1618 1735

ATOM 2969 C GLN B 335 84.930 -44.716 -18.000 1.00 99.77 C

ANISOU 2969 C GLN B 335 13688 13356 10864 -1980 -778 1016 C

ATOM 2970 O GLN B 335 85.207 -45.909 -18.035 1.00 94.32 O

ANISOU 2970 O GLN B 335 13052 12823 9963 -2046 -563 777 O

TER 2974 GLN B 335

HET ATM 2971 O HOH S 1 110.319 -45.601 -9.573 1.00 39.14 O

HETATM 2972 O HOH S 2 112.398 -45.393 -4.628 1.00 48.56 O

HETATM 2973 O HOH S 3 123.141 -29.303 -16.515 1.00 49.19 O

HETATM 2974 O HOH S 4 92.690 -51.029 -13.033 1.00 53.52 O

HETATM 2975 O HOH S 5 93.030 -41.555 0.913 1.00 51.01 O

HETATM 2976 O HOH S 6 128.910 -39.669 -15.753 1.00 51.84 O

HETATM 2977 O HOH S 7 106.614 -30.842 12.237 1.00 54.53 O

HETATM 2978 O HOH S 8 109.156 -39.164 -21.771 1.00 54.08 O ΗΕΤΑΤΜ 29790 HOHS 9 97.811 -30.595 2.170 1.0048.71 O

HETATM 2980 0 HOHS 10 105.036-44.979 -7.282 1.0051.03 o

HET ATM 2981 0 HOHS 12 103.744-48.332 -7.113 1.0059.56 o

HETATM 2982 0 HOHS 13 102.856 -40.999 5.206 1.0060.87 o

HETATM 2983 0 HOHS 14 78.716 -40.614 -2.936 1.0059.21 o

HETATM 2984 0 HOHS 15 89.578 -46.058■■20.621 1.0074.32 o

HETATM 2985 0 HOHS 16 114.649-30.692 -26.795 1.0049.10 o

HETATM 2986 0 HOHS 17 142.633-40.619 -9.003 1.0056.67 o

HETATM 2987 0 HOHS 18 116.936-44.379 -7.204 1.0062.33 o

HETATM 2988 0 HOHS 19 96.204 -29.452 4.025 1.0056.31 o

HETATM 2989 0 HOHS 21 115.084-38.633 -20.997 1.0070.64 o

HETATM 2990 0 HOHS 22 89.198 -28.947 10.760 1.0066.83 o

HETATM 2991 0 HOHS 23 79.979 -40.035 -6.193 1.0070.41 o

HETATM 2992 0 HOHS 24 119.896-43.181 -7.274 1.0054.10 o

HETATM 2993 0 HOHS 25 119.736-51.368 1.322 1.0056.96 o

HETATM 2994 0 HOHS 26 137.748 -60.377 2.044 1.0069.09 o

HETATM 2996 0 HOHS 28 130.865-49.157 -1.725 1.0056.51 o

HETATM 2997 0 HOHS 29 130.133-53.659 -16.917 1.0063.59 o

HETATM 2998 0 HOHS 30 142.632 -49.220 -17.348 1.0053.78 o

HETATM 2999 0 HOHS 31 145.254 -49.889 -7.093 1.0070.96 o

HETATM 3000 0 HOHS 32 147.065-50.187 -11.753 1.0078.79 o

HETATM 3002 0 HOHS 34 122.353 -45.352 -11.824 1.0067.53 o

HETATM 3003 0 HOHS 35 111.792-27.084 -21.446 1.0048.46 o

HETATM 3004 0 HOHS 38 127.029 -40.326 5.304 1.0057.55 o

HETATM 3005 0 HOHS 39 107.501 -23.962 -4.417 1.0055.20 o

HETATM 3006 0 HOHS 40 102.641 -43.919 -7.277 1.0061.10 o

HETATM 3008 0 HOHS 42 103.070-51.992 -16.598 1.0056.67 o

HETATM 3010 0 HOHS 45 101.908-39.022 4.295 1.0065.97 o

HETATM 3011 0 HOHS 46 107.409 -38.986 7.075 1.0071.54 o

HETATM 3012 0 HOHS 47 86.638 -44.011 3.203 1.0060.81 o

HETATM 3013 0 HOHS 49 98.622 -50.649 -8.050 1.0074.15 o

HETATM 3014 0 HOHS 50 105.194 -49.981 -7.010 1.0066.48 o

HETATM 3015 0 HOHS 51 79.285 -43.513 -9.134 1.0057.17 o

HETATM 3016 0 HOHS 52 80.026 -42.362 -7.039 1.0057.20 o

HETATM 3017 0 HOHS 54 108.687-27.481 7.180 1.0056.18 o

HETATM 3018 0 HOHS 55 103.638-29.900 10.927 1.0086.50 o

HETATM 3019 0 HOHS 56 97.777 -23.963 -5.954 1.0059.40 o

HETATM 3021 0 HOHS 59 95.246 -27.230■■16.402 1.0087.80 o

HETATM 3025 0 HOHS 63 82.517 -46.956-■18.723 1.0085.91 o

HETATM 3026 0 HOHS 65 110.613-30.055 -7.221 1.0060.49 o

HETATM 3027 0 HOHS 66 146.283 -49.230 -9.611 1.0099.22 o

HETATM 3028 0 HOHS 67 149.262-52.143 -12.721 1.0077.47 o

HETATM 3029 s S04D 1 124.241 -63.786 - 7.468 1.00144.81 s

HETATM 3030 01 S04D 1 125.494-63.499 -6.774 1.00140.19 o

HETATM 3031 02 S04D 1 124.514-64.163 -8.855 1.00139.55 o

HETATM 3032 03 S04D 1 123.552 -64.891 -6.798 1.00145.34 o

HETATM 3033 04 S04D 1 123.399 -62.594 -7.442 1.00141.27 o

END

Equivalents

[0329] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. The scope of the present invention is not intended to be limited to the above Description, but rather is as set forth in the following claims:

Claims

CLAIMS We claim:

1. A STING modulator whose structure is an analog of c[G(2',5')pA(3',5')p], DMXAA, or CMA, and includes a moiety that interacts with a residue corresponding to Gly230, Gln266, Serl62, or He 165 of hSTING, or a combination thereof.

2. A STING modulator whose structure is an analog of c[G(2',5')pA(3',5')p], DMXAA, or CMA, and includes a moiety that interacts with a residue corresponding to Serl62 and/or He 165 of hSTING.

3. The STING modulator of claim 1 or 2 that modulates hSTING.

4. The STING modulator of any one of the preceding claims, which STING modulator is specific to hSTING as compared with mSTING.

5. The STING modulator of any one of preceding claims, wherein the STING modulator

includes a moiety that interacts with a residue corresponding to Gln266 of hSTING.

6. The STING modulator of any one of preceding claims, wherein the STING modulator

includes a moiety that interacts with a residue corresponding to Gly230 of hSTING.

7. The STING modulator of any one of preceding claims, wherein the STING modulator

includes a moiety that interacts with a residue corresponding to Serl62 of hSTING.

8. The STING modulator of any one of the preceding claims, which STING modulator comprises one or more of the following features:

i. ) direct hydrogen bonds to the side chain of Thr267 of hSTING;

ii. ) direct hydrogen bonds to the side chain of Arg238 of hSTING; and

iii. ) direct hydrogen bonds to the side chain of Thr263 of hSTING.

9. The STING modulator of any one of the preceding claims, which STING modulator comprises one or more of the following features:

i) direct hydrogen bonds to the side chain of Arg238 of hSTING; and

ii) water-mediated hydrogen bonds to Tyr240 of hSTING.

10. The STING modulator of any one of the preceding claims, which STING modulator

comprises one or more of the following features:

i) hydrophobic interactions with a residue corresponding to Leu 170 of hSTING;

ii) hydrophobic interactions with a residue corresponding to Ile235 of hSTING; and

iii) hydrophobic interactions with a residue corresponding to He 165 of hSTING.

11. The STING modulator of any one of the preceding claims, wherein upon binding hSTING, an antiparallel β-pleated sheet forms over the binding pocket indicative of formation of a closed STING conformation.

12. A method of designing or characterizing a STING modulator comprising the steps of:

providing an image of a STING crystal that includes at least one potential interaction site;

docking in the image at least one moiety that is a potential STING modulator structural element; and

assessing one or more features of a potential moiety-interaction site interaction.

13. The method of claim 12, wherein the at least one potential interaction site includes a site of hSTING selected from the group consisting of Serl62, Ilel65, Arg238, Thr263, Thr267, and combinations thereof.

14. The method of claim 12 or 13, wherein the at least one potential interaction site includes a site of hSTING selected from the group consisting of Gly230, Gln266, Tyr240, Leul70, Ile235, and combinations thereof.

15. The method of claim 12, wherein the at least one potential interaction site is Serl62.

16. The method of claim 12, wherein the at least one potential interaction site is Ilel65.

17. The method of claim 12, wherein the at least one potential interaction site is Gly230.

18. The method of any one of claims 12-17, wherein the one or more features include at least one feature selected from the group consisting of: spatial separation between the moiety and the potential interaction site; energy of the potential moiety-interaction site interaction, and/or combinations thereof.

19. The method of any one of claims 12-18, further comprising a step of providing an image of a potential STING modulator comprising the moiety docked with the image of the STING crystal.

20. The method of claim 19, further comprising a step of comparing the image with that of a STING crystal including a bound known modulator.

21. A system comprising a computer or computer readable medium in which a STING crystal structure, or coordinates thereof, is embedded and/or displayed.

22. A method of designing and/or characterizing a STING modulator, which method comprises steps of:

(i) using the sytem of claim 21 to assess one or more structural features of the STING

modulator; and

(ii) performing one or more in vitro, in vivo or cell-based assays to characterize the STING

modulator.

23. The method of claim 22, wherein the one or more structure features of the STING modulator comprise a moiety that interacts with a residue corresponding to Serl62 and/or Ilel65 of hSTING.

24. The method of claim 22 or 23, wherein the one or more structure features of the STING modulator comprise a moiety that interacts with a residue corresponding to Gly230 of hSTING.

25. The method of claim 22, 23, or 24, wherein the one or more structure features of the STING modulator comprise a moiety that interacts with a residue corresponding to Arg238, Thr263, Thr267, Gln266, Tyr240, Leul70, Ile235 of hSTING, or a combination thereof.

26. A method of designing and/or characterizing a STING modulator, which method comprises steps of:

(i) determining the STING modulator binds in the binding pocket having a three-dimensional structure characterized by the structure coordinates of any one of Tables 1, 2, 3, 4, 5, 6, 7, 8, and/or 9; and

(ii) assessing one or more structure features of the STING modulator.

27. The method of claim 26, wherein the method further comprises the step:

(iii) defining the three-dimensional shape of the modulator.

28. The method of claim 26 or 27, wherein the three-dimensional shape of the modulator includes a moiety that interacts with a residue corresponding to Serl62 and/or He 165 of hSTING.

29. The method of claim 26, 27, or 28, wherein the three-dimensional shape of the modulator includes a moiety that interacts with a residue corresponding to Gly230 of hSTING.

30. The method of any one of claims 26-29, wherein the three-dimensional shape of the modulator includes a moiety that interacts with a residue corresponding to Arg238, Thr263, Thr267, Gln266, Tyr240, Leul70, Ile235 of hSTING, or a combination thereof.

31. A designed STING modulator, comprising the crystallography coordinates of any one of Tables 1-9, wherein the crystallography coordinates are within about a root mean square deviation of not more than about 1.5 A from the backbone atoms of the amino acids according to Tables 1, 2, 3, 4, 5, 6, 7, 8, and/or 9.

32. A computer system containing a set of information to perform a design or characterization of a STING modulator having a user interface comprising a display unit, the set of information comprising:

(i) logic for inputting an information regarding a binding of a STING protein to a moiety known to bind STING protein;

(ii) logic for designing a candidate STING modulator based on the binding of the STING protein to the moiety known to bind STING protein;

(iii) logic for determing an information regarding a binding of the STING protein to the

candidate STING modulator; and

(iv) logic for making a conclusion regarding a STING agonist or antagonist properties of the candidate STING modulator based on the determination of step (iii).

33. A computer-readable storage medium containing a set of information for a general purpose computer having a user interface comprising, a display unit, the set of information comprising:

(i) logic for inputting an information regarding a binding of a STING protein to a chemical known to binding STING protein;

(ii) logic for design a candidate STING modulator based on the binding of the STING protein to the chemical known to bind STING protein;

(iii) logic for determining an information regarding a binding of the STING protein to the

candidate STING modulator; and (iv) logic for making a conclusion regarding a STING agonist or antagonist properties of the candidate STING modulator based on the determination step of step (iii).

34. An electronic signal or carrier wave that is propagated over the internet between computers comprising a set of information for a general purpose computer having a user interface comprising a display unit, the set of information comprising a computer-readable storage medium containing a set of information for a general purpose computer having a user interface comprising a display unit, the set of information comprising:

(i) logic for inputting an information regarding a binding of a STING protein to an agent known to bind STING protein;

(ii) logic for designing a candidate STING modulator based on the binding of the STING protein to the agent known to bind STING protein;

(iii) logic for determining an information regarding a binding of the STING protein to the

candidate STING modulator; and

(iv) logic for making a conclusion regarding a STING agonist or antagonist properties of the candidate STING modulator based on the determination of step (iii).

35. A method of modulating activity of a STING polypeptide, the method comprising steps of: contacting the STING polypeptide with a modulating agent of any one of claims 1-11 which modulating agent is not a known modulator.

36. A crystalline or crystallizable composition comprising or consisting of a STING polypeptide.

37. A method of making the composition of claim 36.

38. A method of using the composition of claim 36.