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Database: PDB
Entry: 6EDS
LinkDB: 6EDS
Original site: 6EDS 
HEADER    HYDROLASE/INHIBITOR                     10-AUG-18   6EDS              
TITLE     STRUCTURE OF CYSTEINE-FREE HUMAN INSULIN-DEGRADING ENZYME IN COMPLEX  
TITLE    2 WITH GLUCAGON AND SUBSTRATE-SELECTIVE MACROCYCLIC INHIBITOR 63       
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: INSULIN-DEGRADING ENZYME;                                  
COMPND   3 CHAIN: A, B;                                                         
COMPND   4 SYNONYM: ABETA-DEGRADING PROTEASE,INSULIN PROTEASE,INSULINASE,       
COMPND   5 INSULYSIN;                                                           
COMPND   6 EC: 3.4.24.56;                                                       
COMPND   7 ENGINEERED: YES;                                                     
COMPND   8 MUTATION: YES;                                                       
COMPND   9 MOL_ID: 2;                                                           
COMPND  10 MOLECULE: GLUCAGON;                                                  
COMPND  11 CHAIN: C, D;                                                         
COMPND  12 ENGINEERED: YES;                                                     
COMPND  13 OTHER_DETAILS: GLUCAGON, MARKETED AS GLUCAGEN AND MANUFACTURED BY    
COMPND  14 BOEHRINGER INGELHEIM.                                                
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 GENE: IDE;                                                           
SOURCE   6 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21(DE3);                       
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 469008;                                     
SOURCE   8 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);                                 
SOURCE   9 MOL_ID: 2;                                                           
SOURCE  10 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE  11 ORGANISM_COMMON: HUMAN;                                              
SOURCE  12 ORGANISM_TAXID: 9606;                                                
SOURCE  13 GENE: GCG;                                                           
SOURCE  14 EXPRESSION_SYSTEM: SACCHAROMYCES CEREVISIAE;                         
SOURCE  15 EXPRESSION_SYSTEM_TAXID: 4932                                        
KEYWDS    INSULIN, GLUCAGON, DIABETES, EXO-SITE, HYDROLASE, HYDROLASE-INHIBITOR 
KEYWDS   2 COMPLEX                                                              
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    G.A.TAN,M.A.SEELIGER,J.P.MAIANTI,D.R.LIU,A.J.WELSH                    
REVDAT   3   29-MAY-19 6EDS    1       JRNL                                     
REVDAT   2   17-APR-19 6EDS    1       REMARK                                   
REVDAT   1   03-APR-19 6EDS    0                                                
JRNL        AUTH   J.P.MAIANTI,G.A.TAN,A.VETERE,A.J.WELSH,B.K.WAGNER,           
JRNL        AUTH 2 M.A.SEELIGER,D.R.LIU                                         
JRNL        TITL   SUBSTRATE-SELECTIVE INHIBITORS THAT REPROGRAM THE ACTIVITY   
JRNL        TITL 2 OF INSULIN-DEGRADING ENZYME.                                 
JRNL        REF    NAT.CHEM.BIOL.                V.  15   565 2019              
JRNL        REFN                   ESSN 1552-4469                               
JRNL        PMID   31086331                                                     
JRNL        DOI    10.1038/S41589-019-0271-0                                    
REMARK   1                                                                      
REMARK   1 REFERENCE 1                                                          
REMARK   1  AUTH   J.P.MAIANTI,A.MCFEDRIES,Z.H.FODA,R.E.KLEINER,X.Q.DU,         
REMARK   1  AUTH 2 M.A.LEISSRING,W.J.TANG,M.J.CHARRON,M.A.SEELIGER,             
REMARK   1  AUTH 3 A.SAGHATELIAN,D.R.LIU                                        
REMARK   1  TITL   ANTI-DIABETIC ACTIVITY OF INSULIN-DEGRADING ENZYME           
REMARK   1  TITL 2 INHIBITORS MEDIATED BY MULTIPLE HORMONES.                    
REMARK   1  REF    NATURE                        V. 511    94 2014              
REMARK   1  REFN                   ESSN 1476-4687                               
REMARK   1  PMID   24847884                                                     
REMARK   1  DOI    10.1038/NATURE13297                                          
REMARK   2                                                                      
REMARK   2 RESOLUTION.    3.18 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : PHENIX 1.11.1_2575                                   
REMARK   3   AUTHORS     : PAUL ADAMS,PAVEL AFONINE,VINCENT CHEN,IAN            
REMARK   3               : DAVIS,KRESHNA GOPAL,RALF GROSSE-KUNSTLEVE,           
REMARK   3               : LI-WEI HUNG,ROBERT IMMORMINO,TOM IOERGER,            
REMARK   3               : AIRLIE MCCOY,ERIK MCKEE,NIGEL MORIARTY,              
REMARK   3               : REETAL PAI,RANDY READ,JANE RICHARDSON,               
REMARK   3               : DAVID RICHARDSON,TOD ROMO,JIM SACCHETTINI,           
REMARK   3               : NICHOLAS SAUTER,JACOB SMITH,LAURENT                  
REMARK   3               : STORONI,TOM TERWILLIGER,PETER ZWART                  
REMARK   3                                                                      
REMARK   3    REFINEMENT TARGET : NULL                                          
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 3.18                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 131.56                         
REMARK   3   MIN(FOBS/SIGMA_FOBS)              : 1.336                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 99.9                           
REMARK   3   NUMBER OF REFLECTIONS             : 60257                          
REMARK   3                                                                      
REMARK   3  FIT TO DATA USED IN REFINEMENT.                                     
REMARK   3   R VALUE     (WORKING + TEST SET) : 0.179                           
REMARK   3   R VALUE            (WORKING SET) : 0.177                           
REMARK   3   FREE R VALUE                     : 0.222                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 4.761                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 2869                            
REMARK   3                                                                      
REMARK   3  FIT TO DATA USED IN REFINEMENT (IN BINS).                           
REMARK   3   BIN  RESOLUTION RANGE  COMPL.    NWORK NFREE   RWORK  RFREE        
REMARK   3     1131.6721 -  8.6330    0.99     2954   148  0.1595 0.1781        
REMARK   3     2  8.6330 -  6.8524    1.00     2920   147  0.1530 0.2002        
REMARK   3     3  6.8524 -  5.9862    1.00     2887   144  0.1769 0.2185        
REMARK   3     4  5.9862 -  5.4388    1.00     2898   143  0.1745 0.2127        
REMARK   3     5  5.4388 -  5.0490    1.00     2862   145  0.1525 0.2209        
REMARK   3     6  5.0490 -  4.7513    1.00     2869   143  0.1357 0.1708        
REMARK   3     7  4.7513 -  4.5133    1.00     2876   149  0.1288 0.1552        
REMARK   3     8  4.5133 -  4.3169    1.00     2855   145  0.1365 0.1525        
REMARK   3     9  4.3169 -  4.1507    1.00     2858   140  0.1514 0.2110        
REMARK   3    10  4.1507 -  4.0074    1.00     2892   151  0.1781 0.2335        
REMARK   3    11  4.0074 -  3.8821    1.00     2862   143  0.1926 0.2746        
REMARK   3    12  3.8821 -  3.7711    1.00     2813   138  0.1958 0.2559        
REMARK   3    13  3.7711 -  3.6719    1.00     2892   147  0.1993 0.2755        
REMARK   3    14  3.6719 -  3.5823    1.00     2852   136  0.1992 0.2300        
REMARK   3    15  3.5823 -  3.5008    1.00     2843   142  0.2116 0.2688        
REMARK   3    16  3.5008 -  3.4263    1.00     2849   142  0.2234 0.2758        
REMARK   3    17  3.4263 -  3.3578    1.00     2840   142  0.2421 0.2853        
REMARK   3    18  3.3578 -  3.2944    1.00     2852   143  0.2448 0.3068        
REMARK   3    19  3.2944 -  3.2356    1.00     2847   141  0.2509 0.3164        
REMARK   3    20  3.2356 -  3.1807    1.00     2867   140  0.2401 0.2681        
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELLING.                                             
REMARK   3   METHOD USED        : NULL                                          
REMARK   3   SOLVENT RADIUS     : 1.11                                          
REMARK   3   SHRINKAGE RADIUS   : 0.90                                          
REMARK   3   K_SOL              : NULL                                          
REMARK   3   B_SOL              : NULL                                          
REMARK   3                                                                      
REMARK   3  ERROR ESTIMATES.                                                    
REMARK   3   COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED)     : 0.333            
REMARK   3   PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 21.334           
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 57.90                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 51.59                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : NULL                                                 
REMARK   3    B22 (A**2) : NULL                                                 
REMARK   3    B33 (A**2) : NULL                                                 
REMARK   3    B12 (A**2) : NULL                                                 
REMARK   3    B13 (A**2) : NULL                                                 
REMARK   3    B23 (A**2) : NULL                                                 
REMARK   3                                                                      
REMARK   3  TWINNING INFORMATION.                                               
REMARK   3   FRACTION: NULL                                                     
REMARK   3   OPERATOR: NULL                                                     
REMARK   3                                                                      
REMARK   3  DEVIATIONS FROM IDEAL VALUES.                                       
REMARK   3                 RMSD          COUNT                                  
REMARK   3   BOND      :  0.004          16328                                  
REMARK   3   ANGLE     :  0.645          22100                                  
REMARK   3   CHIRALITY :  0.042           2366                                  
REMARK   3   PLANARITY :  0.004           2850                                  
REMARK   3   DIHEDRAL  : 14.234           9832                                  
REMARK   3                                                                      
REMARK   3  TLS DETAILS                                                         
REMARK   3   NUMBER OF TLS GROUPS  : 1                                          
REMARK   3   TLS GROUP : 1                                                      
REMARK   3    SELECTION: ALL                                                    
REMARK   3    ORIGIN FOR THE GROUP (A):  72.4903 -78.3115   4.8686              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:   0.2196 T22:   0.1995                                     
REMARK   3      T33:   0.1936 T12:  -0.0510                                     
REMARK   3      T13:  -0.0109 T23:  -0.0625                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   0.2584 L22:   0.0635                                     
REMARK   3      L33:   0.0493 L12:   0.1390                                     
REMARK   3      L13:  -0.1330 L23:  -0.1066                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:   0.0309 S12:   0.0273 S13:   0.0002                       
REMARK   3      S21:   0.0177 S22:  -0.0291 S23:  -0.0026                       
REMARK   3      S31:   0.0065 S32:  -0.0307 S33:   0.0012                       
REMARK   3                                                                      
REMARK   3  NCS DETAILS                                                         
REMARK   3   NUMBER OF NCS GROUPS : 2                                           
REMARK   3   NCS GROUP : 1                                                      
REMARK   3    NCS OPERATOR : 1                                                  
REMARK   3     REFERENCE SELECTION: CHAIN 'A'                                   
REMARK   3     SELECTION          : (CHAIN 'B' AND (RESID 43 THROUGH 526 OR     
REMARK   3                          (RESID 527 AND (NAME N OR NAME CA OR NAME   
REMARK   3                          C OR NAME O OR NAME CB )) OR RESID 528      
REMARK   3                          THROUGH 1011))                              
REMARK   3     ATOM PAIRS NUMBER  : NULL                                        
REMARK   3     RMSD               : NULL                                        
REMARK   3   NCS GROUP : 2                                                      
REMARK   3    NCS OPERATOR : 1                                                  
REMARK   3     REFERENCE SELECTION: CHAIN 'C'                                   
REMARK   3     SELECTION          : CHAIN 'D'                                   
REMARK   3     ATOM PAIRS NUMBER  : NULL                                        
REMARK   3     RMSD               : NULL                                        
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: NULL                                      
REMARK   4                                                                      
REMARK   4 6EDS COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 14-AUG-18.                  
REMARK 100 THE DEPOSITION ID IS D_1000236104.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 19-JUL-18                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : 6.8-7.0                            
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : NSLS-II                            
REMARK 200  BEAMLINE                       : 17-ID-2                            
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 0.979341                           
REMARK 200  MONOCHROMATOR                  : NULL                               
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : PIXEL                              
REMARK 200  DETECTOR MANUFACTURER          : DECTRIS EIGER X 16M                
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : XDS                                
REMARK 200  DATA SCALING SOFTWARE          : AUTOPROC                           
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 60302                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 3.180                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 131.559                            
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : NULL                               
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 100.0                              
REMARK 200  DATA REDUNDANCY                : 20.90                              
REMARK 200  R MERGE                    (I) : 0.36900                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 10.9800                            
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 3.18                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 3.24                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : NULL                               
REMARK 200  DATA REDUNDANCY IN SHELL       : NULL                               
REMARK 200  R MERGE FOR SHELL          (I) : NULL                               
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : NULL                               
REMARK 200                                                                      
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH                              
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT        
REMARK 200 SOFTWARE USED: PHASER                                                
REMARK 200 STARTING MODEL: 4LTE                                                 
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 69.32                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 4.01                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1M HEPES PH 7.0, 12% TACSIMATE PH      
REMARK 280  7.0, 13% PEGMME, 10% DIOXANE, VAPOR DIFFUSION, HANGING DROP,        
REMARK 280  TEMPERATURE 298K                                                    
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 65                             
REMARK 290                                                                      
REMARK 290      SYMOP   SYMMETRY                                                
REMARK 290     NNNMMM   OPERATOR                                                
REMARK 290       1555   X,Y,Z                                                   
REMARK 290       2555   -Y,X-Y,Z+2/3                                            
REMARK 290       3555   -X+Y,-X,Z+1/3                                           
REMARK 290       4555   -X,-Y,Z+1/2                                             
REMARK 290       5555   Y,-X+Y,Z+1/6                                            
REMARK 290       6555   X-Y,X,Z+5/6                                             
REMARK 290                                                                      
REMARK 290     WHERE NNN -> OPERATOR NUMBER                                     
REMARK 290           MMM -> TRANSLATION VECTOR                                  
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY TRANSFORMATIONS                            
REMARK 290 THE FOLLOWING TRANSFORMATIONS OPERATE ON THE ATOM/HETATM             
REMARK 290 RECORDS IN THIS ENTRY TO PRODUCE CRYSTALLOGRAPHICALLY                
REMARK 290 RELATED MOLECULES.                                                   
REMARK 290   SMTRY1   1  1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   1  0.000000  1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   1  0.000000  0.000000  1.000000        0.00000            
REMARK 290   SMTRY1   2 -0.500000 -0.866025  0.000000        0.00000            
REMARK 290   SMTRY2   2  0.866025 -0.500000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000       60.21467            
REMARK 290   SMTRY1   3 -0.500000  0.866025  0.000000        0.00000            
REMARK 290   SMTRY2   3 -0.866025 -0.500000  0.000000        0.00000            
REMARK 290   SMTRY3   3  0.000000  0.000000  1.000000       30.10733            
REMARK 290   SMTRY1   4 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   4  0.000000  0.000000  1.000000       45.16100            
REMARK 290   SMTRY1   5  0.500000  0.866025  0.000000        0.00000            
REMARK 290   SMTRY2   5 -0.866025  0.500000  0.000000        0.00000            
REMARK 290   SMTRY3   5  0.000000  0.000000  1.000000       15.05367            
REMARK 290   SMTRY1   6  0.500000 -0.866025  0.000000        0.00000            
REMARK 290   SMTRY2   6  0.866025  0.500000  0.000000        0.00000            
REMARK 290   SMTRY3   6  0.000000  0.000000  1.000000       75.26833            
REMARK 290                                                                      
REMARK 290 REMARK: NULL                                                         
REMARK 300                                                                      
REMARK 300 BIOMOLECULE: 1, 2                                                    
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM                
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN                  
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON               
REMARK 300 BURIED SURFACE AREA.                                                 
REMARK 350                                                                      
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN           
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE                
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS          
REMARK 350 GIVEN BELOW.  BOTH NON-CRYSTALLOGRAPHIC AND                          
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.                               
REMARK 350                                                                      
REMARK 350 BIOMOLECULE: 1                                                       
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: DIMERIC                           
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC                    
REMARK 350 SOFTWARE USED: PISA                                                  
REMARK 350 TOTAL BURIED SURFACE AREA: 2870 ANGSTROM**2                          
REMARK 350 SURFACE AREA OF THE COMPLEX: 37500 ANGSTROM**2                       
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -1.0 KCAL/MOL                         
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, C                                  
REMARK 350   BIOMT1   1  1.000000  0.000000  0.000000        0.00000            
REMARK 350   BIOMT2   1  0.000000  1.000000  0.000000        0.00000            
REMARK 350   BIOMT3   1  0.000000  0.000000  1.000000        0.00000            
REMARK 350                                                                      
REMARK 350 BIOMOLECULE: 2                                                       
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: DIMERIC                           
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC                    
REMARK 350 SOFTWARE USED: PISA                                                  
REMARK 350 TOTAL BURIED SURFACE AREA: 2770 ANGSTROM**2                          
REMARK 350 SURFACE AREA OF THE COMPLEX: 37470 ANGSTROM**2                       
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -1.0 KCAL/MOL                         
REMARK 350 APPLY THE FOLLOWING TO CHAINS: B, D                                  
REMARK 350   BIOMT1   1  1.000000  0.000000  0.000000        0.00000            
REMARK 350   BIOMT2   1  0.000000  1.000000  0.000000        0.00000            
REMARK 350   BIOMT3   1  0.000000  0.000000  1.000000        0.00000            
REMARK 465                                                                      
REMARK 465 MISSING RESIDUES                                                     
REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE                       
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN               
REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)                
REMARK 465                                                                      
REMARK 465   M RES C SSSEQI                                                     
REMARK 465     MET A    42                                                      
REMARK 465     VAL A   968                                                      
REMARK 465     VAL A   969                                                      
REMARK 465     GLY A   970                                                      
REMARK 465     GLU A   971                                                      
REMARK 465     PHE A   972                                                      
REMARK 465     PRO A   973                                                      
REMARK 465     ALA A   974                                                      
REMARK 465     GLN A   975                                                      
REMARK 465     ASN A   976                                                      
REMARK 465     ASP A   977                                                      
REMARK 465     ILE A  1012                                                      
REMARK 465     ASN A  1013                                                      
REMARK 465     PHE A  1014                                                      
REMARK 465     MET A  1015                                                      
REMARK 465     ALA A  1016                                                      
REMARK 465     ALA A  1017                                                      
REMARK 465     LYS A  1018                                                      
REMARK 465     LEU A  1019                                                      
REMARK 465     MET B    42                                                      
REMARK 465     VAL B   968                                                      
REMARK 465     VAL B   969                                                      
REMARK 465     GLY B   970                                                      
REMARK 465     GLU B   971                                                      
REMARK 465     PHE B   972                                                      
REMARK 465     PRO B   973                                                      
REMARK 465     ALA B   974                                                      
REMARK 465     GLN B   975                                                      
REMARK 465     ASN B   976                                                      
REMARK 465     ASP B   977                                                      
REMARK 465     ILE B  1012                                                      
REMARK 465     ASN B  1013                                                      
REMARK 465     PHE B  1014                                                      
REMARK 465     MET B  1015                                                      
REMARK 465     ALA B  1016                                                      
REMARK 465     ALA B  1017                                                      
REMARK 465     LYS B  1018                                                      
REMARK 465     LEU B  1019                                                      
REMARK 465     PHE C     6                                                      
REMARK 465     THR C     7                                                      
REMARK 465     SER C     8                                                      
REMARK 465     ASP C     9                                                      
REMARK 465     TYR C    10                                                      
REMARK 465     SER C    11                                                      
REMARK 465     LYS C    12                                                      
REMARK 465     TYR C    13                                                      
REMARK 465     LEU C    14                                                      
REMARK 465     ASP C    15                                                      
REMARK 465     SER C    16                                                      
REMARK 465     ARG C    17                                                      
REMARK 465     ARG C    18                                                      
REMARK 465     ALA C    19                                                      
REMARK 465     GLN C    20                                                      
REMARK 465     ASP C    21                                                      
REMARK 465     THR C    29                                                      
REMARK 465     PHE D     6                                                      
REMARK 465     THR D     7                                                      
REMARK 465     SER D     8                                                      
REMARK 465     ASP D     9                                                      
REMARK 465     TYR D    10                                                      
REMARK 465     SER D    11                                                      
REMARK 465     LYS D    12                                                      
REMARK 465     TYR D    13                                                      
REMARK 465     LEU D    14                                                      
REMARK 465     ASP D    15                                                      
REMARK 465     SER D    16                                                      
REMARK 465     ARG D    17                                                      
REMARK 465     ARG D    18                                                      
REMARK 465     ALA D    19                                                      
REMARK 465     GLN D    20                                                      
REMARK 465     ASP D    21                                                      
REMARK 465     THR D    29                                                      
REMARK 470                                                                      
REMARK 470 MISSING ATOM                                                         
REMARK 470 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;           
REMARK 470 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;          
REMARK 470 I=INSERTION CODE):                                                   
REMARK 470   M RES CSSEQI  ATOMS                                                
REMARK 470     GLU A 365    CG   CD   OE1  OE2                                  
REMARK 470     LYS A 511    CG   CD   CE   NZ                                   
REMARK 470     LYS A 523    CG   CD   CE   NZ                                   
REMARK 470     LYS A 527    CG   CD   CE   NZ                                   
REMARK 470     LYS A 542    CG   CD   CE   NZ                                   
REMARK 470     GLU A 543    CG   CD   OE1  OE2                                  
REMARK 470     LYS A 657    CG   CD   CE   NZ                                   
REMARK 470     VAL A 764    CG1  CG2                                            
REMARK 470     ASP A 964    CG   OD1  OD2                                       
REMARK 470     ASN A 966    CG   OD1  ND2                                       
REMARK 470     ILE A 978    CG1  CG2  CD1                                       
REMARK 470     ASN A 979    CG   OD1  ND2                                       
REMARK 470     LYS A1009    CG   CD   CE   NZ                                   
REMARK 470     GLU B 365    CG   CD   OE1  OE2                                  
REMARK 470     LYS B 511    CG   CD   CE   NZ                                   
REMARK 470     LYS B 523    CG   CD   CE   NZ                                   
REMARK 470     LYS B 542    CG   CD   CE   NZ                                   
REMARK 470     GLU B 543    CG   CD   OE1  OE2                                  
REMARK 470     LYS B 657    CG   CD   CE   NZ                                   
REMARK 470     VAL B 764    CG1  CG2                                            
REMARK 470     ASP B 964    CG   OD1  OD2                                       
REMARK 470     ASN B 966    CG   OD1  ND2                                       
REMARK 470     ILE B 978    CG1  CG2  CD1                                       
REMARK 470     ASN B 979    CG   OD1  ND2                                       
REMARK 470     LYS B1009    CG   CD   CE   NZ                                   
REMARK 470     PHE C  22    N                                                   
REMARK 470     PHE D  22    N                                                   
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT                     
REMARK 500                                                                      
REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.                            
REMARK 500                                                                      
REMARK 500  ATM1  RES C  SSEQI   ATM2  RES C  SSEQI           DISTANCE          
REMARK 500   O    LEU B   944     NH1  ARG B   951              1.97            
REMARK 500   OE2  GLU A   864     NH2  ARG A   951              2.08            
REMARK 500   OE2  GLU B   864     NH2  ARG B   951              2.10            
REMARK 500   O    LEU A   944     NH1  ARG A   951              2.15            
REMARK 500   OG   SER A   557     OE2  GLU A   746              2.17            
REMARK 500   O    MET A   877     NZ   LYS A   933              2.18            
REMARK 500   NZ   LYS B   906     OD2  ASP B   921              2.19            
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: CLOSE CONTACTS                                             
REMARK 500                                                                      
REMARK 500 THE FOLLOWING ATOMS THAT ARE RELATED BY CRYSTALLOGRAPHIC             
REMARK 500 SYMMETRY ARE IN CLOSE CONTACT.  AN ATOM LOCATED WITHIN 0.15          
REMARK 500 ANGSTROMS OF A SYMMETRY RELATED ATOM IS ASSUMED TO BE ON A           
REMARK 500 SPECIAL POSITION AND IS, THEREFORE, LISTED IN REMARK 375             
REMARK 500 INSTEAD OF REMARK 500.  ATOMS WITH NON-BLANK ALTERNATE               
REMARK 500 LOCATION INDICATORS ARE NOT INCLUDED IN THE CALCULATIONS.            
REMARK 500                                                                      
REMARK 500 DISTANCE CUTOFF:                                                     
REMARK 500 2.2 ANGSTROMS FOR CONTACTS NOT INVOLVING HYDROGEN ATOMS              
REMARK 500 1.6 ANGSTROMS FOR CONTACTS INVOLVING HYDROGEN ATOMS                  
REMARK 500                                                                      
REMARK 500  ATM1  RES C  SSEQI   ATM2  RES C  SSEQI  SSYMOP   DISTANCE          
REMARK 500   OE2  GLU A   233     OG   SER B   246     1554     2.08            
REMARK 500   OE2  GLU A   408     OG1  THR A   734     2544     2.19            
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: COVALENT BOND ANGLES                                       
REMARK 500                                                                      
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES              
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE               
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN               
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).                 
REMARK 500                                                                      
REMARK 500 STANDARD TABLE:                                                      
REMARK 500 FORMAT: (10X,I3,1X,A3,1X,A1,I4,A1,3(1X,A4,2X),12X,F5.1)              
REMARK 500                                                                      
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999                        
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996                     
REMARK 500                                                                      
REMARK 500  M RES CSSEQI ATM1   ATM2   ATM3                                     
REMARK 500    PRO B 967   C   -  N   -  CA  ANGL. DEV. =  11.0 DEGREES          
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: TORSION ANGLES                                             
REMARK 500                                                                      
REMARK 500 TORSION ANGLES OUTSIDE THE EXPECTED RAMACHANDRAN REGIONS:            
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;               
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).                             
REMARK 500                                                                      
REMARK 500 STANDARD TABLE:                                                      
REMARK 500 FORMAT:(10X,I3,1X,A3,1X,A1,I4,A1,4X,F7.2,3X,F7.2)                    
REMARK 500                                                                      
REMARK 500 EXPECTED VALUES: GJ KLEYWEGT AND TA JONES (1996). PHI/PSI-           
REMARK 500 CHOLOGY: RAMACHANDRAN REVISITED. STRUCTURE 4, 1395 - 1400            
REMARK 500                                                                      
REMARK 500  M RES CSSEQI        PSI       PHI                                   
REMARK 500    HIS A  53      132.98    -37.83                                   
REMARK 500    HIS A  93       42.51    -75.43                                   
REMARK 500    LEU A 116       42.23    -93.63                                   
REMARK 500    LEU A 170      -51.25   -133.37                                   
REMARK 500    SER A 171       67.04   -150.36                                   
REMARK 500    GLU A 227      -62.55   -139.32                                   
REMARK 500    GLN A 294     -168.11   -102.63                                   
REMARK 500    TYR A 325       39.02    -81.56                                   
REMARK 500    TYR A 454      -61.44   -109.90                                   
REMARK 500    GLU A 457      -55.67   -126.54                                   
REMARK 500    ARG A 460       78.35   -119.34                                   
REMARK 500    ASN A 515       44.12    -90.06                                   
REMARK 500    ASP A 517      178.60    -59.33                                   
REMARK 500    LYS A 566      -39.02   -137.09                                   
REMARK 500    TYR A 584       15.80   -145.22                                   
REMARK 500    THR A 797      -81.69    -99.08                                   
REMARK 500    ARG A 824      -65.99   -103.86                                   
REMARK 500    SER A 965      101.20    -58.99                                   
REMARK 500    PRO A1006     -163.20    -70.91                                   
REMARK 500    HIS B  93       41.74    -74.79                                   
REMARK 500    LEU B 116       44.44    -92.77                                   
REMARK 500    LEU B 170      -52.16   -133.37                                   
REMARK 500    SER B 171       67.30   -152.20                                   
REMARK 500    GLU B 227      -64.08   -140.44                                   
REMARK 500    GLN B 294     -166.13   -105.15                                   
REMARK 500    TYR B 325       33.51    -82.63                                   
REMARK 500    GLU B 457      -68.22   -124.03                                   
REMARK 500    ARG B 460       77.42   -115.86                                   
REMARK 500    ASN B 515       43.28    -90.99                                   
REMARK 500    ASP B 517      176.48    -58.85                                   
REMARK 500    LYS B 566      -38.85   -137.21                                   
REMARK 500    TYR B 584       16.22   -145.28                                   
REMARK 500    THR B 797      -81.20    -98.91                                   
REMARK 500    ARG B 824      -65.76   -103.02                                   
REMARK 500    ASN B 917       79.27   -101.59                                   
REMARK 500    SER B 965      106.35    -58.04                                   
REMARK 500    PRO B1006     -163.66    -68.97                                   
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 800                                                                      
REMARK 800 SITE                                                                 
REMARK 800 SITE_IDENTIFIER: AC1                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue J22 A 1101                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue EPE A 1102                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue PEG A 1103                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC4                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue DIO A 1104                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC5                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue EPE B 1101                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC6                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue PEG B 1102                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC7                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue DIO B 1103                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC8                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue J22 B 1104                
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 4LTE   RELATED DB: PDB                                   
REMARK 900 4LTE IS OF IDE IN COMPLEX WITH AN EARLIER GENERATION MACROCYCLIC     
REMARK 900 LIGAND FROM OUR GROUP                                                
REMARK 900 RELATED ID: 6BYZ   RELATED DB: PDB                                   
REMARK 900 6BYZ IS OUR UNRELEASED STRUCTURE OF IDE IN COMPLEX WITH J18, A       
REMARK 900 MACROCYCLIC INHIBITOR                                                
REMARK 900 RELATED ID: 2G49   RELATED DB: PDB                                   
REMARK 900 2G49 IS A STRUCTURE OF GLUCAGON-BOUND IDE                            
DBREF  6EDS A   42  1019  UNP    P14735   IDE_HUMAN       42   1019             
DBREF  6EDS B   42  1019  UNP    P14735   IDE_HUMAN       42   1019             
DBREF  6EDS C    1    29  UNP    P01275   GLUC_HUMAN      53     81             
DBREF  6EDS D    1    29  UNP    P01275   GLUC_HUMAN      53     81             
SEQADV 6EDS LEU A  110  UNP  P14735    CYS   110 ENGINEERED MUTATION            
SEQADV 6EDS GLN A  111  UNP  P14735    GLU   111 ENGINEERED MUTATION            
SEQADV 6EDS SER A  171  UNP  P14735    CYS   171 ENGINEERED MUTATION            
SEQADV 6EDS ALA A  178  UNP  P14735    CYS   178 ENGINEERED MUTATION            
SEQADV 6EDS VAL A  257  UNP  P14735    CYS   257 ENGINEERED MUTATION            
SEQADV 6EDS LEU A  414  UNP  P14735    CYS   414 ENGINEERED MUTATION            
SEQADV 6EDS ASN A  573  UNP  P14735    CYS   573 ENGINEERED MUTATION            
SEQADV 6EDS SER A  590  UNP  P14735    CYS   590 ENGINEERED MUTATION            
SEQADV 6EDS SER A  789  UNP  P14735    CYS   789 ENGINEERED MUTATION            
SEQADV 6EDS ALA A  812  UNP  P14735    CYS   812 ENGINEERED MUTATION            
SEQADV 6EDS ALA A  819  UNP  P14735    CYS   819 ENGINEERED MUTATION            
SEQADV 6EDS SER A  904  UNP  P14735    CYS   904 ENGINEERED MUTATION            
SEQADV 6EDS ASN A  966  UNP  P14735    CYS   966 ENGINEERED MUTATION            
SEQADV 6EDS ALA A  974  UNP  P14735    CYS   974 ENGINEERED MUTATION            
SEQADV 6EDS LEU B  110  UNP  P14735    CYS   110 ENGINEERED MUTATION            
SEQADV 6EDS GLN B  111  UNP  P14735    GLU   111 ENGINEERED MUTATION            
SEQADV 6EDS SER B  171  UNP  P14735    CYS   171 ENGINEERED MUTATION            
SEQADV 6EDS ALA B  178  UNP  P14735    CYS   178 ENGINEERED MUTATION            
SEQADV 6EDS VAL B  257  UNP  P14735    CYS   257 ENGINEERED MUTATION            
SEQADV 6EDS LEU B  414  UNP  P14735    CYS   414 ENGINEERED MUTATION            
SEQADV 6EDS ASN B  573  UNP  P14735    CYS   573 ENGINEERED MUTATION            
SEQADV 6EDS SER B  590  UNP  P14735    CYS   590 ENGINEERED MUTATION            
SEQADV 6EDS SER B  789  UNP  P14735    CYS   789 ENGINEERED MUTATION            
SEQADV 6EDS ALA B  812  UNP  P14735    CYS   812 ENGINEERED MUTATION            
SEQADV 6EDS ALA B  819  UNP  P14735    CYS   819 ENGINEERED MUTATION            
SEQADV 6EDS SER B  904  UNP  P14735    CYS   904 ENGINEERED MUTATION            
SEQADV 6EDS ASN B  966  UNP  P14735    CYS   966 ENGINEERED MUTATION            
SEQADV 6EDS ALA B  974  UNP  P14735    CYS   974 ENGINEERED MUTATION            
SEQRES   1 A  978  MET ASN ASN PRO ALA ILE LYS ARG ILE GLY ASN HIS ILE          
SEQRES   2 A  978  THR LYS SER PRO GLU ASP LYS ARG GLU TYR ARG GLY LEU          
SEQRES   3 A  978  GLU LEU ALA ASN GLY ILE LYS VAL LEU LEU ILE SER ASP          
SEQRES   4 A  978  PRO THR THR ASP LYS SER SER ALA ALA LEU ASP VAL HIS          
SEQRES   5 A  978  ILE GLY SER LEU SER ASP PRO PRO ASN ILE ALA GLY LEU          
SEQRES   6 A  978  SER HIS PHE LEU GLN HIS MET LEU PHE LEU GLY THR LYS          
SEQRES   7 A  978  LYS TYR PRO LYS GLU ASN GLU TYR SER GLN PHE LEU SER          
SEQRES   8 A  978  GLU HIS ALA GLY SER SER ASN ALA PHE THR SER GLY GLU          
SEQRES   9 A  978  HIS THR ASN TYR TYR PHE ASP VAL SER HIS GLU HIS LEU          
SEQRES  10 A  978  GLU GLY ALA LEU ASP ARG PHE ALA GLN PHE PHE LEU SER          
SEQRES  11 A  978  PRO LEU PHE ASP GLU SER ALA LYS ASP ARG GLU VAL ASN          
SEQRES  12 A  978  ALA VAL ASP SER GLU HIS GLU LYS ASN VAL MET ASN ASP          
SEQRES  13 A  978  ALA TRP ARG LEU PHE GLN LEU GLU LYS ALA THR GLY ASN          
SEQRES  14 A  978  PRO LYS HIS PRO PHE SER LYS PHE GLY THR GLY ASN LYS          
SEQRES  15 A  978  TYR THR LEU GLU THR ARG PRO ASN GLN GLU GLY ILE ASP          
SEQRES  16 A  978  VAL ARG GLN GLU LEU LEU LYS PHE HIS SER ALA TYR TYR          
SEQRES  17 A  978  SER SER ASN LEU MET ALA VAL VAL VAL LEU GLY ARG GLU          
SEQRES  18 A  978  SER LEU ASP ASP LEU THR ASN LEU VAL VAL LYS LEU PHE          
SEQRES  19 A  978  SER GLU VAL GLU ASN LYS ASN VAL PRO LEU PRO GLU PHE          
SEQRES  20 A  978  PRO GLU HIS PRO PHE GLN GLU GLU HIS LEU LYS GLN LEU          
SEQRES  21 A  978  TYR LYS ILE VAL PRO ILE LYS ASP ILE ARG ASN LEU TYR          
SEQRES  22 A  978  VAL THR PHE PRO ILE PRO ASP LEU GLN LYS TYR TYR LYS          
SEQRES  23 A  978  SER ASN PRO GLY HIS TYR LEU GLY HIS LEU ILE GLY HIS          
SEQRES  24 A  978  GLU GLY PRO GLY SER LEU LEU SER GLU LEU LYS SER LYS          
SEQRES  25 A  978  GLY TRP VAL ASN THR LEU VAL GLY GLY GLN LYS GLU GLY          
SEQRES  26 A  978  ALA ARG GLY PHE MET PHE PHE ILE ILE ASN VAL ASP LEU          
SEQRES  27 A  978  THR GLU GLU GLY LEU LEU HIS VAL GLU ASP ILE ILE LEU          
SEQRES  28 A  978  HIS MET PHE GLN TYR ILE GLN LYS LEU ARG ALA GLU GLY          
SEQRES  29 A  978  PRO GLN GLU TRP VAL PHE GLN GLU LEU LYS ASP LEU ASN          
SEQRES  30 A  978  ALA VAL ALA PHE ARG PHE LYS ASP LYS GLU ARG PRO ARG          
SEQRES  31 A  978  GLY TYR THR SER LYS ILE ALA GLY ILE LEU HIS TYR TYR          
SEQRES  32 A  978  PRO LEU GLU GLU VAL LEU THR ALA GLU TYR LEU LEU GLU          
SEQRES  33 A  978  GLU PHE ARG PRO ASP LEU ILE GLU MET VAL LEU ASP LYS          
SEQRES  34 A  978  LEU ARG PRO GLU ASN VAL ARG VAL ALA ILE VAL SER LYS          
SEQRES  35 A  978  SER PHE GLU GLY LYS THR ASP ARG THR GLU GLU TRP TYR          
SEQRES  36 A  978  GLY THR GLN TYR LYS GLN GLU ALA ILE PRO ASP GLU VAL          
SEQRES  37 A  978  ILE LYS LYS TRP GLN ASN ALA ASP LEU ASN GLY LYS PHE          
SEQRES  38 A  978  LYS LEU PRO THR LYS ASN GLU PHE ILE PRO THR ASN PHE          
SEQRES  39 A  978  GLU ILE LEU PRO LEU GLU LYS GLU ALA THR PRO TYR PRO          
SEQRES  40 A  978  ALA LEU ILE LYS ASP THR ALA MET SER LYS LEU TRP PHE          
SEQRES  41 A  978  LYS GLN ASP ASP LYS PHE PHE LEU PRO LYS ALA ASN LEU          
SEQRES  42 A  978  ASN PHE GLU PHE PHE SER PRO PHE ALA TYR VAL ASP PRO          
SEQRES  43 A  978  LEU HIS SER ASN MET ALA TYR LEU TYR LEU GLU LEU LEU          
SEQRES  44 A  978  LYS ASP SER LEU ASN GLU TYR ALA TYR ALA ALA GLU LEU          
SEQRES  45 A  978  ALA GLY LEU SER TYR ASP LEU GLN ASN THR ILE TYR GLY          
SEQRES  46 A  978  MET TYR LEU SER VAL LYS GLY TYR ASN ASP LYS GLN PRO          
SEQRES  47 A  978  ILE LEU LEU LYS LYS ILE ILE GLU LYS MET ALA THR PHE          
SEQRES  48 A  978  GLU ILE ASP GLU LYS ARG PHE GLU ILE ILE LYS GLU ALA          
SEQRES  49 A  978  TYR MET ARG SER LEU ASN ASN PHE ARG ALA GLU GLN PRO          
SEQRES  50 A  978  HIS GLN HIS ALA MET TYR TYR LEU ARG LEU LEU MET THR          
SEQRES  51 A  978  GLU VAL ALA TRP THR LYS ASP GLU LEU LYS GLU ALA LEU          
SEQRES  52 A  978  ASP ASP VAL THR LEU PRO ARG LEU LYS ALA PHE ILE PRO          
SEQRES  53 A  978  GLN LEU LEU SER ARG LEU HIS ILE GLU ALA LEU LEU HIS          
SEQRES  54 A  978  GLY ASN ILE THR LYS GLN ALA ALA LEU GLY ILE MET GLN          
SEQRES  55 A  978  MET VAL GLU ASP THR LEU ILE GLU HIS ALA HIS THR LYS          
SEQRES  56 A  978  PRO LEU LEU PRO SER GLN LEU VAL ARG TYR ARG GLU VAL          
SEQRES  57 A  978  GLN LEU PRO ASP ARG GLY TRP PHE VAL TYR GLN GLN ARG          
SEQRES  58 A  978  ASN GLU VAL HIS ASN ASN SER GLY ILE GLU ILE TYR TYR          
SEQRES  59 A  978  GLN THR ASP MET GLN SER THR SER GLU ASN MET PHE LEU          
SEQRES  60 A  978  GLU LEU PHE ALA GLN ILE ILE SER GLU PRO ALA PHE ASN          
SEQRES  61 A  978  THR LEU ARG THR LYS GLU GLN LEU GLY TYR ILE VAL PHE          
SEQRES  62 A  978  SER GLY PRO ARG ARG ALA ASN GLY ILE GLN GLY LEU ARG          
SEQRES  63 A  978  PHE ILE ILE GLN SER GLU LYS PRO PRO HIS TYR LEU GLU          
SEQRES  64 A  978  SER ARG VAL GLU ALA PHE LEU ILE THR MET GLU LYS SER          
SEQRES  65 A  978  ILE GLU ASP MET THR GLU GLU ALA PHE GLN LYS HIS ILE          
SEQRES  66 A  978  GLN ALA LEU ALA ILE ARG ARG LEU ASP LYS PRO LYS LYS          
SEQRES  67 A  978  LEU SER ALA GLU SER ALA LYS TYR TRP GLY GLU ILE ILE          
SEQRES  68 A  978  SER GLN GLN TYR ASN PHE ASP ARG ASP ASN THR GLU VAL          
SEQRES  69 A  978  ALA TYR LEU LYS THR LEU THR LYS GLU ASP ILE ILE LYS          
SEQRES  70 A  978  PHE TYR LYS GLU MET LEU ALA VAL ASP ALA PRO ARG ARG          
SEQRES  71 A  978  HIS LYS VAL SER VAL HIS VAL LEU ALA ARG GLU MET ASP          
SEQRES  72 A  978  SER ASN PRO VAL VAL GLY GLU PHE PRO ALA GLN ASN ASP          
SEQRES  73 A  978  ILE ASN LEU SER GLN ALA PRO ALA LEU PRO GLN PRO GLU          
SEQRES  74 A  978  VAL ILE GLN ASN MET THR GLU PHE LYS ARG GLY LEU PRO          
SEQRES  75 A  978  LEU PHE PRO LEU VAL LYS PRO HIS ILE ASN PHE MET ALA          
SEQRES  76 A  978  ALA LYS LEU                                                  
SEQRES   1 B  978  MET ASN ASN PRO ALA ILE LYS ARG ILE GLY ASN HIS ILE          
SEQRES   2 B  978  THR LYS SER PRO GLU ASP LYS ARG GLU TYR ARG GLY LEU          
SEQRES   3 B  978  GLU LEU ALA ASN GLY ILE LYS VAL LEU LEU ILE SER ASP          
SEQRES   4 B  978  PRO THR THR ASP LYS SER SER ALA ALA LEU ASP VAL HIS          
SEQRES   5 B  978  ILE GLY SER LEU SER ASP PRO PRO ASN ILE ALA GLY LEU          
SEQRES   6 B  978  SER HIS PHE LEU GLN HIS MET LEU PHE LEU GLY THR LYS          
SEQRES   7 B  978  LYS TYR PRO LYS GLU ASN GLU TYR SER GLN PHE LEU SER          
SEQRES   8 B  978  GLU HIS ALA GLY SER SER ASN ALA PHE THR SER GLY GLU          
SEQRES   9 B  978  HIS THR ASN TYR TYR PHE ASP VAL SER HIS GLU HIS LEU          
SEQRES  10 B  978  GLU GLY ALA LEU ASP ARG PHE ALA GLN PHE PHE LEU SER          
SEQRES  11 B  978  PRO LEU PHE ASP GLU SER ALA LYS ASP ARG GLU VAL ASN          
SEQRES  12 B  978  ALA VAL ASP SER GLU HIS GLU LYS ASN VAL MET ASN ASP          
SEQRES  13 B  978  ALA TRP ARG LEU PHE GLN LEU GLU LYS ALA THR GLY ASN          
SEQRES  14 B  978  PRO LYS HIS PRO PHE SER LYS PHE GLY THR GLY ASN LYS          
SEQRES  15 B  978  TYR THR LEU GLU THR ARG PRO ASN GLN GLU GLY ILE ASP          
SEQRES  16 B  978  VAL ARG GLN GLU LEU LEU LYS PHE HIS SER ALA TYR TYR          
SEQRES  17 B  978  SER SER ASN LEU MET ALA VAL VAL VAL LEU GLY ARG GLU          
SEQRES  18 B  978  SER LEU ASP ASP LEU THR ASN LEU VAL VAL LYS LEU PHE          
SEQRES  19 B  978  SER GLU VAL GLU ASN LYS ASN VAL PRO LEU PRO GLU PHE          
SEQRES  20 B  978  PRO GLU HIS PRO PHE GLN GLU GLU HIS LEU LYS GLN LEU          
SEQRES  21 B  978  TYR LYS ILE VAL PRO ILE LYS ASP ILE ARG ASN LEU TYR          
SEQRES  22 B  978  VAL THR PHE PRO ILE PRO ASP LEU GLN LYS TYR TYR LYS          
SEQRES  23 B  978  SER ASN PRO GLY HIS TYR LEU GLY HIS LEU ILE GLY HIS          
SEQRES  24 B  978  GLU GLY PRO GLY SER LEU LEU SER GLU LEU LYS SER LYS          
SEQRES  25 B  978  GLY TRP VAL ASN THR LEU VAL GLY GLY GLN LYS GLU GLY          
SEQRES  26 B  978  ALA ARG GLY PHE MET PHE PHE ILE ILE ASN VAL ASP LEU          
SEQRES  27 B  978  THR GLU GLU GLY LEU LEU HIS VAL GLU ASP ILE ILE LEU          
SEQRES  28 B  978  HIS MET PHE GLN TYR ILE GLN LYS LEU ARG ALA GLU GLY          
SEQRES  29 B  978  PRO GLN GLU TRP VAL PHE GLN GLU LEU LYS ASP LEU ASN          
SEQRES  30 B  978  ALA VAL ALA PHE ARG PHE LYS ASP LYS GLU ARG PRO ARG          
SEQRES  31 B  978  GLY TYR THR SER LYS ILE ALA GLY ILE LEU HIS TYR TYR          
SEQRES  32 B  978  PRO LEU GLU GLU VAL LEU THR ALA GLU TYR LEU LEU GLU          
SEQRES  33 B  978  GLU PHE ARG PRO ASP LEU ILE GLU MET VAL LEU ASP LYS          
SEQRES  34 B  978  LEU ARG PRO GLU ASN VAL ARG VAL ALA ILE VAL SER LYS          
SEQRES  35 B  978  SER PHE GLU GLY LYS THR ASP ARG THR GLU GLU TRP TYR          
SEQRES  36 B  978  GLY THR GLN TYR LYS GLN GLU ALA ILE PRO ASP GLU VAL          
SEQRES  37 B  978  ILE LYS LYS TRP GLN ASN ALA ASP LEU ASN GLY LYS PHE          
SEQRES  38 B  978  LYS LEU PRO THR LYS ASN GLU PHE ILE PRO THR ASN PHE          
SEQRES  39 B  978  GLU ILE LEU PRO LEU GLU LYS GLU ALA THR PRO TYR PRO          
SEQRES  40 B  978  ALA LEU ILE LYS ASP THR ALA MET SER LYS LEU TRP PHE          
SEQRES  41 B  978  LYS GLN ASP ASP LYS PHE PHE LEU PRO LYS ALA ASN LEU          
SEQRES  42 B  978  ASN PHE GLU PHE PHE SER PRO PHE ALA TYR VAL ASP PRO          
SEQRES  43 B  978  LEU HIS SER ASN MET ALA TYR LEU TYR LEU GLU LEU LEU          
SEQRES  44 B  978  LYS ASP SER LEU ASN GLU TYR ALA TYR ALA ALA GLU LEU          
SEQRES  45 B  978  ALA GLY LEU SER TYR ASP LEU GLN ASN THR ILE TYR GLY          
SEQRES  46 B  978  MET TYR LEU SER VAL LYS GLY TYR ASN ASP LYS GLN PRO          
SEQRES  47 B  978  ILE LEU LEU LYS LYS ILE ILE GLU LYS MET ALA THR PHE          
SEQRES  48 B  978  GLU ILE ASP GLU LYS ARG PHE GLU ILE ILE LYS GLU ALA          
SEQRES  49 B  978  TYR MET ARG SER LEU ASN ASN PHE ARG ALA GLU GLN PRO          
SEQRES  50 B  978  HIS GLN HIS ALA MET TYR TYR LEU ARG LEU LEU MET THR          
SEQRES  51 B  978  GLU VAL ALA TRP THR LYS ASP GLU LEU LYS GLU ALA LEU          
SEQRES  52 B  978  ASP ASP VAL THR LEU PRO ARG LEU LYS ALA PHE ILE PRO          
SEQRES  53 B  978  GLN LEU LEU SER ARG LEU HIS ILE GLU ALA LEU LEU HIS          
SEQRES  54 B  978  GLY ASN ILE THR LYS GLN ALA ALA LEU GLY ILE MET GLN          
SEQRES  55 B  978  MET VAL GLU ASP THR LEU ILE GLU HIS ALA HIS THR LYS          
SEQRES  56 B  978  PRO LEU LEU PRO SER GLN LEU VAL ARG TYR ARG GLU VAL          
SEQRES  57 B  978  GLN LEU PRO ASP ARG GLY TRP PHE VAL TYR GLN GLN ARG          
SEQRES  58 B  978  ASN GLU VAL HIS ASN ASN SER GLY ILE GLU ILE TYR TYR          
SEQRES  59 B  978  GLN THR ASP MET GLN SER THR SER GLU ASN MET PHE LEU          
SEQRES  60 B  978  GLU LEU PHE ALA GLN ILE ILE SER GLU PRO ALA PHE ASN          
SEQRES  61 B  978  THR LEU ARG THR LYS GLU GLN LEU GLY TYR ILE VAL PHE          
SEQRES  62 B  978  SER GLY PRO ARG ARG ALA ASN GLY ILE GLN GLY LEU ARG          
SEQRES  63 B  978  PHE ILE ILE GLN SER GLU LYS PRO PRO HIS TYR LEU GLU          
SEQRES  64 B  978  SER ARG VAL GLU ALA PHE LEU ILE THR MET GLU LYS SER          
SEQRES  65 B  978  ILE GLU ASP MET THR GLU GLU ALA PHE GLN LYS HIS ILE          
SEQRES  66 B  978  GLN ALA LEU ALA ILE ARG ARG LEU ASP LYS PRO LYS LYS          
SEQRES  67 B  978  LEU SER ALA GLU SER ALA LYS TYR TRP GLY GLU ILE ILE          
SEQRES  68 B  978  SER GLN GLN TYR ASN PHE ASP ARG ASP ASN THR GLU VAL          
SEQRES  69 B  978  ALA TYR LEU LYS THR LEU THR LYS GLU ASP ILE ILE LYS          
SEQRES  70 B  978  PHE TYR LYS GLU MET LEU ALA VAL ASP ALA PRO ARG ARG          
SEQRES  71 B  978  HIS LYS VAL SER VAL HIS VAL LEU ALA ARG GLU MET ASP          
SEQRES  72 B  978  SER ASN PRO VAL VAL GLY GLU PHE PRO ALA GLN ASN ASP          
SEQRES  73 B  978  ILE ASN LEU SER GLN ALA PRO ALA LEU PRO GLN PRO GLU          
SEQRES  74 B  978  VAL ILE GLN ASN MET THR GLU PHE LYS ARG GLY LEU PRO          
SEQRES  75 B  978  LEU PHE PRO LEU VAL LYS PRO HIS ILE ASN PHE MET ALA          
SEQRES  76 B  978  ALA LYS LEU                                                  
SEQRES   1 C   29  HIS SER GLN GLY THR PHE THR SER ASP TYR SER LYS TYR          
SEQRES   2 C   29  LEU ASP SER ARG ARG ALA GLN ASP PHE VAL GLN TRP LEU          
SEQRES   3 C   29  MET ASN THR                                                  
SEQRES   1 D   29  HIS SER GLN GLY THR PHE THR SER ASP TYR SER LYS TYR          
SEQRES   2 D   29  LEU ASP SER ARG ARG ALA GLN ASP PHE VAL GLN TRP LEU          
SEQRES   3 D   29  MET ASN THR                                                  
HET    J22  A1101      69                                                       
HET    EPE  A1102      32                                                       
HET    PEG  A1103      17                                                       
HET    DIO  A1104      14                                                       
HET    EPE  B1101      32                                                       
HET    PEG  B1102      17                                                       
HET    DIO  B1103      14                                                       
HET    J22  B1104      69                                                       
HETNAM     J22 {(8R,9S,10S)-9-(2',3'-DIMETHYL[1,1'-BIPHENYL]-4-YL)-6-           
HETNAM   2 J22  [(1-METHYL-1H-IMIDAZOL-2-YL)SULFONYL]-1,6-                      
HETNAM   3 J22  DIAZABICYCLO[6.2.0]DECAN-10-YL}METHANOL                         
HETNAM     EPE 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID              
HETNAM     PEG DI(HYDROXYETHYL)ETHER                                            
HETNAM     DIO 1,4-DIETHYLENE DIOXIDE                                           
HETSYN     EPE HEPES                                                            
FORMUL   5  J22    2(C27 H34 N4 O3 S)                                           
FORMUL   6  EPE    2(C8 H18 N2 O4 S)                                            
FORMUL   7  PEG    2(C4 H10 O3)                                                 
FORMUL   8  DIO    2(C4 H8 O2)                                                  
HELIX    1 AA1 GLY A   95  ASP A   99  5                                   5    
HELIX    2 AA2 GLY A  105  PHE A  115  1                                  11    
HELIX    3 AA3 ASN A  125  GLU A  133  1                                   9    
HELIX    4 AA4 HIS A  157  GLN A  167  1                                  11    
HELIX    5 AA5 PHE A  168  LEU A  170  5                                   3    
HELIX    6 AA6 ASP A  175  MET A  195  1                                  21    
HELIX    7 AA7 ASN A  196  GLY A  209  1                                  14    
HELIX    8 AA8 HIS A  213  LYS A  217  5                                   5    
HELIX    9 AA9 ASN A  222  GLU A  227  1                                   6    
HELIX   10 AB1 GLU A  227  GLU A  233  1                                   7    
HELIX   11 AB2 ASP A  236  TYR A  249  1                                  14    
HELIX   12 AB3 SER A  250  ASN A  252  5                                   3    
HELIX   13 AB4 SER A  263  SER A  276  1                                  14    
HELIX   14 AB5 GLN A  294  LEU A  298  5                                   5    
HELIX   15 AB6 LEU A  322  TYR A  326  5                                   5    
HELIX   16 AB7 ASN A  329  GLY A  339  1                                  11    
HELIX   17 AB8 SER A  345  LYS A  353  1                                   9    
HELIX   18 AB9 THR A  380  HIS A  386  1                                   7    
HELIX   19 AC1 HIS A  386  GLY A  405  1                                  20    
HELIX   20 AC2 GLN A  407  PHE A  424  1                                  18    
HELIX   21 AC3 ARG A  429  LEU A  441  1                                  13    
HELIX   22 AC4 ARG A  460  LEU A  471  1                                  12    
HELIX   23 AC5 ARG A  472  ASN A  475  5                                   4    
HELIX   24 AC6 SER A  484  GLU A  486  5                                   3    
HELIX   25 AC7 PRO A  506  ASN A  515  1                                  10    
HELIX   26 AC8 PRO A  581  TYR A  584  5                                   4    
HELIX   27 AC9 ASP A  586  ALA A  614  1                                  29    
HELIX   28 AD1 LYS A  637  THR A  651  1                                  15    
HELIX   29 AD2 ASP A  655  ASN A  672  1                                  18    
HELIX   30 AD3 PHE A  673  GLU A  676  5                                   4    
HELIX   31 AD4 GLN A  677  THR A  691  1                                  15    
HELIX   32 AD5 THR A  696  LEU A  704  1                                   9    
HELIX   33 AD6 ASP A  705  VAL A  707  5                                   3    
HELIX   34 AD7 THR A  708  SER A  721  1                                  14    
HELIX   35 AD8 THR A  734  HIS A  754  1                                  21    
HELIX   36 AD9 LEU A  759  LEU A  763  5                                   5    
HELIX   37 AE1 SER A  801  ARG A  824  1                                  24    
HELIX   38 AE2 PRO A  855  MET A  877  1                                  23    
HELIX   39 AE3 THR A  878  LEU A  894  1                                  17    
HELIX   40 AE4 LYS A  899  SER A  913  1                                  15    
HELIX   41 AE5 ASP A  919  LEU A  931  1                                  13    
HELIX   42 AE6 THR A  932  LEU A  944  1                                  13    
HELIX   43 AE7 ASN A  994  GLY A 1001  1                                   8    
HELIX   44 AE8 GLY B   95  ASP B   99  5                                   5    
HELIX   45 AE9 GLY B  105  PHE B  115  1                                  11    
HELIX   46 AF1 ASN B  125  GLU B  133  1                                   9    
HELIX   47 AF2 HIS B  157  GLN B  167  1                                  11    
HELIX   48 AF3 PHE B  168  LEU B  170  5                                   3    
HELIX   49 AF4 ASP B  175  MET B  195  1                                  21    
HELIX   50 AF5 ASN B  196  GLY B  209  1                                  14    
HELIX   51 AF6 HIS B  213  LYS B  217  5                                   5    
HELIX   52 AF7 ASN B  222  GLU B  227  1                                   6    
HELIX   53 AF8 GLU B  227  GLU B  233  1                                   7    
HELIX   54 AF9 ASP B  236  TYR B  249  1                                  14    
HELIX   55 AG1 SER B  250  ASN B  252  5                                   3    
HELIX   56 AG2 SER B  263  SER B  276  1                                  14    
HELIX   57 AG3 GLN B  294  LEU B  298  5                                   5    
HELIX   58 AG4 LEU B  322  SER B  328  5                                   7    
HELIX   59 AG5 ASN B  329  GLY B  339  1                                  11    
HELIX   60 AG6 SER B  345  LYS B  353  1                                   9    
HELIX   61 AG7 THR B  380  HIS B  386  1                                   7    
HELIX   62 AG8 HIS B  386  GLY B  405  1                                  20    
HELIX   63 AG9 GLN B  407  PHE B  424  1                                  18    
HELIX   64 AH1 ARG B  429  LEU B  441  1                                  13    
HELIX   65 AH2 GLU B  448  GLU B  453  1                                   6    
HELIX   66 AH3 ARG B  460  LEU B  471  1                                  12    
HELIX   67 AH4 ARG B  472  ASN B  475  5                                   4    
HELIX   68 AH5 SER B  484  GLU B  486  5                                   3    
HELIX   69 AH6 PRO B  506  ASN B  515  1                                  10    
HELIX   70 AH7 PRO B  581  TYR B  584  5                                   4    
HELIX   71 AH8 ASP B  586  ALA B  614  1                                  29    
HELIX   72 AH9 LYS B  637  THR B  651  1                                  15    
HELIX   73 AI1 ASP B  655  ASN B  672  1                                  18    
HELIX   74 AI2 PHE B  673  GLU B  676  5                                   4    
HELIX   75 AI3 GLN B  677  THR B  691  1                                  15    
HELIX   76 AI4 THR B  696  LEU B  704  1                                   9    
HELIX   77 AI5 ASP B  705  VAL B  707  5                                   3    
HELIX   78 AI6 THR B  708  SER B  721  1                                  14    
HELIX   79 AI7 THR B  734  HIS B  754  1                                  21    
HELIX   80 AI8 LEU B  759  LEU B  763  5                                   5    
HELIX   81 AI9 SER B  801  ARG B  824  1                                  24    
HELIX   82 AJ1 PRO B  855  MET B  877  1                                  23    
HELIX   83 AJ2 THR B  878  LEU B  894  1                                  17    
HELIX   84 AJ3 LYS B  899  SER B  913  1                                  15    
HELIX   85 AJ4 ASP B  919  THR B  930  1                                  12    
HELIX   86 AJ5 THR B  932  LEU B  944  1                                  13    
HELIX   87 AJ6 ASN B  994  GLY B 1001  1                                   8    
SHEET    1 AA1 8 ILE A  47  GLY A  51  0                                        
SHEET    2 AA1 8 GLU A  63  LEU A  69 -1  O  GLY A  66   N  GLY A  51           
SHEET    3 AA1 8 LYS A  74  SER A  79 -1  O  VAL A  75   N  LEU A  67           
SHEET    4 AA1 8 MET A 254  GLY A 260  1  O  VAL A 258   N  ILE A  78           
SHEET    5 AA1 8 LYS A  85  VAL A  92 -1  N  SER A  87   O  LEU A 259           
SHEET    6 AA1 8 THR A 147  SER A 154 -1  O  TYR A 149   N  LEU A  90           
SHEET    7 AA1 8 SER A 137  THR A 142 -1  N  SER A 137   O  ASP A 152           
SHEET    8 AA1 8 GLN C  24  TRP C  25 -1  O  GLN C  24   N  THR A 142           
SHEET    1 AA2 7 LEU A 359  GLU A 365  0                                        
SHEET    2 AA2 7 MET A 371  ASP A 378 -1  O  ASN A 376   N  VAL A 360           
SHEET    3 AA2 7 ARG A 311  ILE A 319 -1  N  LEU A 313   O  VAL A 377           
SHEET    4 AA2 7 ARG A 477  SER A 482 -1  O  VAL A 481   N  ASN A 312           
SHEET    5 AA2 7 GLN A 300  ILE A 304  1  N  TYR A 302   O  ILE A 480           
SHEET    6 AA2 7 GLN A 499  ALA A 504 -1  O  GLU A 503   N  LEU A 301           
SHEET    7 AA2 7 ARG A 491  THR A 492 -1  N  ARG A 491   O  TYR A 500           
SHEET    1 AA3 6 ALA A 549  ASP A 553  0                                        
SHEET    2 AA3 6 SER A 557  GLN A 563 -1  O  PHE A 561   N  ALA A 549           
SHEET    3 AA3 6 ARG A 722  GLY A 731  1  O  ALA A 727   N  TRP A 560           
SHEET    4 AA3 6 LYS A 571  PHE A 579 -1  N  ASN A 573   O  HIS A 730           
SHEET    5 AA3 6 GLY A 626  TYR A 634 -1  O  MET A 627   N  PHE A 578           
SHEET    6 AA3 6 LEU A 616  THR A 623 -1  N  ASP A 619   O  SER A 630           
SHEET    1 AA4 4 ALA A 549  ASP A 553  0                                        
SHEET    2 AA4 4 SER A 557  GLN A 563 -1  O  PHE A 561   N  ALA A 549           
SHEET    3 AA4 4 ARG A 722  GLY A 731  1  O  ALA A 727   N  TRP A 560           
SHEET    4 AA4 4 LYS A 756  PRO A 757  1  O  LYS A 756   N  LEU A 723           
SHEET    1 AA5 6 ILE A 832  ALA A 840  0                                        
SHEET    2 AA5 6 ILE A 843  SER A 852 -1  O  ILE A 843   N  ALA A 840           
SHEET    3 AA5 6 SER A 789  MET A 799 -1  N  TYR A 795   O  LEU A 846           
SHEET    4 AA5 6 HIS A 952  LEU A 959 -1  O  VAL A 958   N  GLY A 790           
SHEET    5 AA5 6 GLY A 775  ARG A 782  1  N  GLN A 781   O  LEU A 959           
SHEET    6 AA5 6 GLU A 990  ILE A 992  1  O  GLU A 990   N  TRP A 776           
SHEET    1 AA6 8 ILE B  47  GLY B  51  0                                        
SHEET    2 AA6 8 GLU B  63  LEU B  69 -1  O  GLY B  66   N  GLY B  51           
SHEET    3 AA6 8 LYS B  74  SER B  79 -1  O  VAL B  75   N  LEU B  67           
SHEET    4 AA6 8 MET B 254  GLY B 260  1  O  VAL B 258   N  ILE B  78           
SHEET    5 AA6 8 LYS B  85  VAL B  92 -1  N  SER B  87   O  LEU B 259           
SHEET    6 AA6 8 THR B 147  SER B 154 -1  O  TYR B 149   N  LEU B  90           
SHEET    7 AA6 8 SER B 137  THR B 142 -1  N  PHE B 141   O  ASN B 148           
SHEET    8 AA6 8 GLN D  24  TRP D  25 -1  O  GLN D  24   N  THR B 142           
SHEET    1 AA7 7 LEU B 359  LYS B 364  0                                        
SHEET    2 AA7 7 PHE B 370  ASP B 378 -1  O  ASN B 376   N  VAL B 360           
SHEET    3 AA7 7 ARG B 311  PRO B 320 -1  N  ILE B 319   O  MET B 371           
SHEET    4 AA7 7 ARG B 477  SER B 482 -1  O  ALA B 479   N  TYR B 314           
SHEET    5 AA7 7 GLN B 300  ILE B 304  1  N  TYR B 302   O  ILE B 480           
SHEET    6 AA7 7 GLN B 499  ALA B 504 -1  O  GLU B 503   N  LEU B 301           
SHEET    7 AA7 7 ARG B 491  THR B 492 -1  N  ARG B 491   O  TYR B 500           
SHEET    1 AA8 6 ALA B 549  ASP B 553  0                                        
SHEET    2 AA8 6 SER B 557  GLN B 563 -1  O  PHE B 561   N  ALA B 549           
SHEET    3 AA8 6 ARG B 722  GLY B 731  1  O  ALA B 727   N  TRP B 560           
SHEET    4 AA8 6 LYS B 571  PHE B 579 -1  N  ASN B 573   O  HIS B 730           
SHEET    5 AA8 6 GLY B 626  TYR B 634 -1  O  MET B 627   N  PHE B 578           
SHEET    6 AA8 6 LEU B 616  THR B 623 -1  N  ASP B 619   O  SER B 630           
SHEET    1 AA9 4 ALA B 549  ASP B 553  0                                        
SHEET    2 AA9 4 SER B 557  GLN B 563 -1  O  PHE B 561   N  ALA B 549           
SHEET    3 AA9 4 ARG B 722  GLY B 731  1  O  ALA B 727   N  TRP B 560           
SHEET    4 AA9 4 LYS B 756  PRO B 757  1  O  LYS B 756   N  LEU B 723           
SHEET    1 AB1 6 ILE B 832  ALA B 840  0                                        
SHEET    2 AB1 6 ILE B 843  SER B 852 -1  O  ILE B 849   N  PHE B 834           
SHEET    3 AB1 6 SER B 789  MET B 799 -1  N  TYR B 795   O  LEU B 846           
SHEET    4 AB1 6 HIS B 952  LEU B 959 -1  O  VAL B 958   N  GLY B 790           
SHEET    5 AB1 6 GLY B 775  ARG B 782  1  N  GLN B 781   O  LEU B 959           
SHEET    6 AB1 6 GLU B 990  VAL B 991  1  O  GLU B 990   N  TRP B 776           
SITE     1 AC1 17 ALA A 198  LEU A 201  PHE A 202  GLU A 205                    
SITE     2 AC1 17 TYR A 302  TYR A 314  THR A 316  VAL A 360                    
SITE     3 AC1 17 GLN A 363  LYS A 364  ILE A 374  ASN A 376                    
SITE     4 AC1 17 ARG A 477  ALA A 479  GLN C   3  THR C   5                    
SITE     5 AC1 17 PHE C  22                                                     
SITE     1 AC2  7 GLN A 800  ARG A 839  ALA A 840  ASN A 841                    
SITE     2 AC2  7 GLY A 842  SER A 913  GLN A 915                               
SITE     1 AC3  8 GLU A 408  LEU A 538  ASN A 635  GLN A 638                    
SITE     2 AC3  8 ASN A 732  ILE A 733  THR A 734  ALA A 737                    
SITE     1 AC4  3 GLU A 529  PHE A 530  ILE A 640                               
SITE     1 AC5  7 GLN B 800  ARG B 839  ALA B 840  ASN B 841                    
SITE     2 AC5  7 GLY B 842  SER B 913  ARG B 920                               
SITE     1 AC6  6 LEU B 538  ASN B 635  GLN B 638  ASN B 732                    
SITE     2 AC6  6 ILE B 733  ALA B 737                                          
SITE     1 AC7  2 GLU B 529  ILE B 640                                          
SITE     1 AC8 15 ALA B 198  LEU B 201  PHE B 202  GLU B 205                    
SITE     2 AC8 15 TYR B 302  THR B 316  VAL B 360  LYS B 364                    
SITE     3 AC8 15 ILE B 374  ASN B 376  ARG B 477  ALA B 479                    
SITE     4 AC8 15 GLN D   3  THR D   5  PHE D  22                               
CRYST1  263.119  263.119   90.322  90.00  90.00 120.00 P 65         12          
ORIGX1      1.000000  0.000000  0.000000        0.00000                         
ORIGX2      0.000000  1.000000  0.000000        0.00000                         
ORIGX3      0.000000  0.000000  1.000000        0.00000                         
SCALE1      0.003801  0.002194  0.000000        0.00000                         
SCALE2      0.000000  0.004389  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.011071        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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