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Database: PDB
Entry: 2I0H
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Original site: 2I0H 
HEADER    TRANSFERASE                             10-AUG-06   2I0H              
TITLE     THE STRUCTURE OF P38ALPHA IN COMPLEX WITH AN ARYLPYRIDAZINONE         
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: MITOGEN-ACTIVATED PROTEIN KINASE 14;                       
COMPND   3 CHAIN: A;                                                            
COMPND   4 SYNONYM: MITOGEN-ACTIVATED PROTEIN KINASE P38 ALPHA, MAP KINASE P38  
COMPND   5 ALPHA, CYTOKINE SUPPRESSIVE ANTI-INFLAMMATORY DRUG-BINDING PROTEIN,  
COMPND   6 CSAID-BINDING PROTEIN, CSBP, MAX-INTERACTING PROTEIN 2, MAP KINASE   
COMPND   7 MXI2, SAPK2A;                                                        
COMPND   8 EC: 2.7.11.24;                                                       
COMPND   9 ENGINEERED: YES;                                                     
COMPND  10 MUTATION: YES                                                        
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 GENE: MAPK14, CSBP, CSBP1, CSBP2, MXI2;                              
SOURCE   6 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21(DE3);                       
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 469008;                                     
SOURCE   8 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);                                 
SOURCE   9 EXPRESSION_SYSTEM_PLASMID: PET                                       
KEYWDS    SERINE/THREONINE KINASE, INHIBITOR DESIGN, TRANSFERASE                
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    S.R.NATARAJAN,S.T.HELLER,K.NAM,S.B.SINGH,G.SCAPIN,S.PATEL,            
AUTHOR   2 J.E.THOMPSON,C.E.FITZGERALD,S.J.O'KEEFE                              
REVDAT   5   18-OCT-17 2I0H    1       REMARK                                   
REVDAT   4   13-JUL-11 2I0H    1       VERSN                                    
REVDAT   3   24-FEB-09 2I0H    1       VERSN                                    
REVDAT   2   07-NOV-06 2I0H    1       JRNL                                     
REVDAT   1   17-OCT-06 2I0H    0                                                
JRNL        AUTH   S.R.NATARAJAN,S.T.HELLER,K.NAM,S.B.SINGH,G.SCAPIN,S.PATEL,   
JRNL        AUTH 2 C.E.FITZGERALD,J.E.THOMPSON,S.J.O'KEEFE                      
JRNL        TITL   P38 MAP KINASE INHIBITORS PART 6: 2-ARYLPYRIDAZIN-3-ONES AS  
JRNL        TITL 2 TEMPLATES FOR INHIBITOR DESIGN.                              
JRNL        REF    BIOORG.MED.CHEM.LETT.         V.  16  5809 2006              
JRNL        REFN                   ISSN 0960-894X                               
JRNL        PMID   16945533                                                     
JRNL        DOI    10.1016/J.BMCL.2006.08.074                                   
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.00 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : CNS                                                  
REMARK   3   AUTHORS     : BRUNGER,ADAMS,CLORE,DELANO,GROS,GROSSE-              
REMARK   3               : KUNSTLEVE,JIANG,KUSZEWSKI,NILGES,PANNU,              
REMARK   3               : READ,RICE,SIMONSON,WARREN                            
REMARK   3                                                                      
REMARK   3  REFINEMENT TARGET : ENGH & HUBER                                    
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 2.00                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 30.00                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 0.000                          
REMARK   3   DATA CUTOFF HIGH         (ABS(F)) : NULL                           
REMARK   3   DATA CUTOFF LOW          (ABS(F)) : NULL                           
REMARK   3   COMPLETENESS (WORKING+TEST)   (%) : 97.7                           
REMARK   3   NUMBER OF REFLECTIONS             : 30985                          
REMARK   3                                                                      
REMARK   3  FIT TO DATA USED IN REFINEMENT.                                     
REMARK   3   CROSS-VALIDATION METHOD          : THROUGHOUT                      
REMARK   3   FREE R VALUE TEST SET SELECTION  : RANDOM                          
REMARK   3   R VALUE            (WORKING SET) : 0.178                           
REMARK   3   FREE R VALUE                     : 0.228                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 5.000                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 1613                            
REMARK   3   ESTIMATED ERROR OF FREE R VALUE  : NULL                            
REMARK   3                                                                      
REMARK   3  FIT IN THE HIGHEST RESOLUTION BIN.                                  
REMARK   3   TOTAL NUMBER OF BINS USED           : NULL                         
REMARK   3   BIN RESOLUTION RANGE HIGH       (A) : 2.00                         
REMARK   3   BIN RESOLUTION RANGE LOW        (A) : 2.07                         
REMARK   3   BIN COMPLETENESS (WORKING+TEST) (%) : 87.60                        
REMARK   3   REFLECTIONS IN BIN    (WORKING SET) : 2735                         
REMARK   3   BIN R VALUE           (WORKING SET) : 0.2240                       
REMARK   3   BIN FREE R VALUE                    : 0.2420                       
REMARK   3   BIN FREE R VALUE TEST SET SIZE  (%) : 5.00                         
REMARK   3   BIN FREE R VALUE TEST SET COUNT     : 138                          
REMARK   3   ESTIMATED ERROR OF BIN FREE R VALUE : NULL                         
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 2807                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 86                                      
REMARK   3   SOLVENT ATOMS            : 455                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 19.00                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 21.40                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : 2.58900                                              
REMARK   3    B22 (A**2) : 1.80500                                              
REMARK   3    B33 (A**2) : -4.93400                                             
REMARK   3    B12 (A**2) : 0.00000                                              
REMARK   3    B13 (A**2) : 0.00000                                              
REMARK   3    B23 (A**2) : 0.00000                                              
REMARK   3                                                                      
REMARK   3  ESTIMATED COORDINATE ERROR.                                         
REMARK   3   ESD FROM LUZZATI PLOT        (A) : 0.20                            
REMARK   3   ESD FROM SIGMAA              (A) : NULL                            
REMARK   3   LOW RESOLUTION CUTOFF        (A) : 5.00                            
REMARK   3                                                                      
REMARK   3  CROSS-VALIDATED ESTIMATED COORDINATE ERROR.                         
REMARK   3   ESD FROM C-V LUZZATI PLOT    (A) : NULL                            
REMARK   3   ESD FROM C-V SIGMAA          (A) : NULL                            
REMARK   3                                                                      
REMARK   3  RMS DEVIATIONS FROM IDEAL VALUES.                                   
REMARK   3   BOND LENGTHS                 (A) : 0.012                           
REMARK   3   BOND ANGLES            (DEGREES) : 1.440                           
REMARK   3   DIHEDRAL ANGLES        (DEGREES) : 22.31                           
REMARK   3   IMPROPER ANGLES        (DEGREES) : 0.900                           
REMARK   3                                                                      
REMARK   3  ISOTROPIC THERMAL MODEL : ANISOTROPIC                               
REMARK   3                                                                      
REMARK   3  ISOTROPIC THERMAL FACTOR RESTRAINTS.    RMS    SIGMA                
REMARK   3   MAIN-CHAIN BOND              (A**2) : 1.420 ; 2.000                
REMARK   3   MAIN-CHAIN ANGLE             (A**2) : 2.444 ; 2.500                
REMARK   3   SIDE-CHAIN BOND              (A**2) : 1.906 ; 2.500                
REMARK   3   SIDE-CHAIN ANGLE             (A**2) : 2.936 ; 3.000                
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELING.                                              
REMARK   3   METHOD USED : MASK                                                 
REMARK   3   KSOL        : 0.36                                                 
REMARK   3   BSOL        : 41.96                                                
REMARK   3                                                                      
REMARK   3  NCS MODEL : NULL                                                    
REMARK   3                                                                      
REMARK   3  NCS RESTRAINTS.                         RMS   SIGMA/WEIGHT          
REMARK   3   GROUP  1  POSITIONAL            (A) : NULL  ; NULL                 
REMARK   3   GROUP  1  B-FACTOR           (A**2) : NULL  ; NULL                 
REMARK   3                                                                      
REMARK   3  PARAMETER FILE  1  : NULL                                           
REMARK   3  TOPOLOGY FILE  1   : NULL                                           
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: NULL                                      
REMARK   4                                                                      
REMARK   4 2I0H COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 11-AUG-06.                  
REMARK 100 THE DEPOSITION ID IS D_1000038982.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 15-DEC-01                          
REMARK 200  TEMPERATURE           (KELVIN) : 100.0                              
REMARK 200  PH                             : 7.00                               
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : APS                                
REMARK 200  BEAMLINE                       : 17-BM                              
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.00                               
REMARK 200  MONOCHROMATOR                  : NULL                               
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : CCD                                
REMARK 200  DETECTOR MANUFACTURER          : MARRESEARCH                        
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : DENZO                              
REMARK 200  DATA SCALING SOFTWARE          : SCALEPACK                          
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 32668                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.000                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 30.000                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : -3.000                             
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 97.8                               
REMARK 200  DATA REDUNDANCY                : 6.600                              
REMARK 200  R MERGE                    (I) : 0.09300                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 4.9000                             
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.00                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 2.07                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 87.7                               
REMARK 200  DATA REDUNDANCY IN SHELL       : 5.90                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.36700                            
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 1.800                              
REMARK 200                                                                      
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH                              
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: FOURIER SYNTHESIS            
REMARK 200 SOFTWARE USED: CNS                                                   
REMARK 200 STARTING MODEL: PDB ENTRY 1WFC                                       
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 56.88                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.85                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: SODIUM CITRATE, AMMONIUM SULFATE,        
REMARK 280  HEPES, PH 7.00, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 284K     
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 21                       
REMARK 290                                                                      
REMARK 290      SYMOP   SYMMETRY                                                
REMARK 290     NNNMMM   OPERATOR                                                
REMARK 290       1555   X,Y,Z                                                   
REMARK 290       2555   -X+1/2,-Y,Z+1/2                                         
REMARK 290       3555   -X,Y+1/2,-Z+1/2                                         
REMARK 290       4555   X+1/2,-Y+1/2,-Z                                         
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 -1.000000  0.000000  0.000000       22.36100            
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000       60.72800            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       44.11250            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000       60.72800            
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000       22.36100            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       44.11250            
REMARK 290   SMTRY3   4  0.000000  0.000000 -1.000000        0.00000            
REMARK 290                                                                      
REMARK 290 REMARK: NULL                                                         
REMARK 300                                                                      
REMARK 300 BIOMOLECULE: 1                                                       
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: MONOMERIC                         
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A                                     
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     GLY A    -5                                                      
REMARK 465     SER A    -4                                                      
REMARK 465     HIS A    -3                                                      
REMARK 465     MET A    -2                                                      
REMARK 465     LEU A    -1                                                      
REMARK 465     GLU A     0                                                      
REMARK 465     MET A     1                                                      
REMARK 465     SER A     2                                                      
REMARK 465     GLN A     3                                                      
REMARK 465     LEU A   353                                                      
REMARK 465     ASP A   354                                                      
REMARK 465     GLN A   355                                                      
REMARK 465     GLU A   356                                                      
REMARK 465     GLU A   357                                                      
REMARK 465     MET A   358                                                      
REMARK 465     GLU A   359                                                      
REMARK 465     SER A   360                                                      
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     LYS A  15    CG   CD   CE   NZ                                   
REMARK 470     ARG A 173    CG   CD   NE   CZ   NH1  NH2                        
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    LYS A  15       17.49     58.80                                   
REMARK 500    ASN A 100       20.21   -152.58                                   
REMARK 500    ASN A 100       16.55   -152.58                                   
REMARK 500    ASP A 145       32.18     72.05                                   
REMARK 500    ARG A 149      -16.34     79.92                                   
REMARK 500    ASP A 150       43.98   -146.02                                   
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 222 A 400                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 222 A 3400                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL A 1004                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC4                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL A 1005                
DBREF  2I0H A    1   360  UNP    Q16539   MK14_HUMAN       1    360             
SEQADV 2I0H GLY A   -5  UNP  Q16539              CLONING ARTIFACT               
SEQADV 2I0H SER A   -4  UNP  Q16539              CLONING ARTIFACT               
SEQADV 2I0H HIS A   -3  UNP  Q16539              CLONING ARTIFACT               
SEQADV 2I0H MET A   -2  UNP  Q16539              CLONING ARTIFACT               
SEQADV 2I0H LEU A   -1  UNP  Q16539              CLONING ARTIFACT               
SEQADV 2I0H GLU A    0  UNP  Q16539              CLONING ARTIFACT               
SEQADV 2I0H SER A  162  UNP  Q16539    CYS   162 ENGINEERED                     
SEQRES   1 A  366  GLY SER HIS MET LEU GLU MET SER GLN GLU ARG PRO THR          
SEQRES   2 A  366  PHE TYR ARG GLN GLU LEU ASN LYS THR ILE TRP GLU VAL          
SEQRES   3 A  366  PRO GLU ARG TYR GLN ASN LEU SER PRO VAL GLY SER GLY          
SEQRES   4 A  366  ALA TYR GLY SER VAL CYS ALA ALA PHE ASP THR LYS THR          
SEQRES   5 A  366  GLY LEU ARG VAL ALA VAL LYS LYS LEU SER ARG PRO PHE          
SEQRES   6 A  366  GLN SER ILE ILE HIS ALA LYS ARG THR TYR ARG GLU LEU          
SEQRES   7 A  366  ARG LEU LEU LYS HIS MET LYS HIS GLU ASN VAL ILE GLY          
SEQRES   8 A  366  LEU LEU ASP VAL PHE THR PRO ALA ARG SER LEU GLU GLU          
SEQRES   9 A  366  PHE ASN ASP VAL TYR LEU VAL THR HIS LEU MET GLY ALA          
SEQRES  10 A  366  ASP LEU ASN ASN ILE VAL LYS CYS GLN LYS LEU THR ASP          
SEQRES  11 A  366  ASP HIS VAL GLN PHE LEU ILE TYR GLN ILE LEU ARG GLY          
SEQRES  12 A  366  LEU LYS TYR ILE HIS SER ALA ASP ILE ILE HIS ARG ASP          
SEQRES  13 A  366  LEU LYS PRO SER ASN LEU ALA VAL ASN GLU ASP SER GLU          
SEQRES  14 A  366  LEU LYS ILE LEU ASP PHE GLY LEU ALA ARG HIS THR ASP          
SEQRES  15 A  366  ASP GLU MET THR GLY TYR VAL ALA THR ARG TRP TYR ARG          
SEQRES  16 A  366  ALA PRO GLU ILE MET LEU ASN TRP MET HIS TYR ASN GLN          
SEQRES  17 A  366  THR VAL ASP ILE TRP SER VAL GLY CYS ILE MET ALA GLU          
SEQRES  18 A  366  LEU LEU THR GLY ARG THR LEU PHE PRO GLY THR ASP HIS          
SEQRES  19 A  366  ILE ASP GLN LEU LYS LEU ILE LEU ARG LEU VAL GLY THR          
SEQRES  20 A  366  PRO GLY ALA GLU LEU LEU LYS LYS ILE SER SER GLU SER          
SEQRES  21 A  366  ALA ARG ASN TYR ILE GLN SER LEU THR GLN MET PRO LYS          
SEQRES  22 A  366  MET ASN PHE ALA ASN VAL PHE ILE GLY ALA ASN PRO LEU          
SEQRES  23 A  366  ALA VAL ASP LEU LEU GLU LYS MET LEU VAL LEU ASP SER          
SEQRES  24 A  366  ASP LYS ARG ILE THR ALA ALA GLN ALA LEU ALA HIS ALA          
SEQRES  25 A  366  TYR PHE ALA GLN TYR HIS ASP PRO ASP ASP GLU PRO VAL          
SEQRES  26 A  366  ALA ASP PRO TYR ASP GLN SER PHE GLU SER ARG ASP LEU          
SEQRES  27 A  366  LEU ILE ASP GLU TRP LYS SER LEU THR TYR ASP GLU VAL          
SEQRES  28 A  366  ILE SER PHE VAL PRO PRO PRO LEU ASP GLN GLU GLU MET          
SEQRES  29 A  366  GLU SER                                                      
HET    222  A 400      37                                                       
HET    222  A3400      37                                                       
HET    GOL  A1004       6                                                       
HET    GOL  A1005       6                                                       
HETNAM     222 2-(3-{(2-CHLORO-4-FLUOROPHENYL)[1-(2-CHLOROPHENYL)-6-            
HETNAM   2 222  OXO-1,6-DIHYDROPYRIDAZIN-3-YL]AMINO}PROPYL)-1H-                 
HETNAM   3 222  ISOINDOLE-1,3(2H)-DIONE                                         
HETNAM     GOL GLYCEROL                                                         
HETSYN     GOL GLYCERIN; PROPANE-1,2,3-TRIOL                                    
FORMUL   2  222    2(C27 H19 CL2 F N4 O3)                                       
FORMUL   4  GOL    2(C3 H8 O3)                                                  
FORMUL   6  HOH   *455(H2 O)                                                    
HELIX    1   1 GLY A   31  ALA A   34  5                                   4    
HELIX    2   2 SER A   61  MET A   78  1                                  18    
HELIX    3   3 LEU A  113  LYS A  118  1                                   6    
HELIX    4   4 THR A  123  ALA A  144  1                                  22    
HELIX    5   5 LYS A  152  SER A  154  5                                   3    
HELIX    6   6 ASP A  176  THR A  180  5                                   5    
HELIX    7   7 VAL A  183  TYR A  188  1                                   6    
HELIX    8   8 ALA A  190  LEU A  195  1                                   6    
HELIX    9   9 GLN A  202  GLY A  219  1                                  18    
HELIX   10  10 ASP A  227  GLY A  240  1                                  14    
HELIX   11  11 GLY A  243  ILE A  250  1                                   8    
HELIX   12  12 SER A  252  GLN A  260  1                                   9    
HELIX   13  13 ASN A  269  PHE A  274  1                                   6    
HELIX   14  14 ASN A  278  LEU A  289  1                                  12    
HELIX   15  15 ASP A  292  ARG A  296  5                                   5    
HELIX   16  16 THR A  298  ALA A  304  1                                   7    
HELIX   17  17 HIS A  305  ALA A  309  5                                   5    
HELIX   18  18 GLN A  325  ARG A  330  5                                   6    
HELIX   19  19 LEU A  333  SER A  347  1                                  15    
SHEET    1   A 2 PHE A   8  LEU A  13  0                                        
SHEET    2   A 2 THR A  16  PRO A  21 -1  O  THR A  16   N  LEU A  13           
SHEET    1   B 5 TYR A  24  PRO A  29  0                                        
SHEET    2   B 5 SER A  37  ASP A  43 -1  O  ALA A  40   N  SER A  28           
SHEET    3   B 5 ARG A  49  SER A  56 -1  O  VAL A  52   N  CYS A  39           
SHEET    4   B 5 ASP A 101  HIS A 107 -1  O  VAL A 102   N  LEU A  55           
SHEET    5   B 5 ASP A  88  PHE A  90 -1  N  ASP A  88   O  VAL A 105           
SHEET    1   C 3 ALA A 111  ASP A 112  0                                        
SHEET    2   C 3 LEU A 156  VAL A 158 -1  O  VAL A 158   N  ALA A 111           
SHEET    3   C 3 LEU A 164  ILE A 166 -1  O  LYS A 165   N  ALA A 157           
SITE     1 AC1 15 TYR A  35  VAL A  38  ALA A  51  LYS A  53                    
SITE     2 AC1 15 LEU A  75  LEU A 104  THR A 106  HIS A 107                    
SITE     3 AC1 15 LEU A 108  MET A 109  GLY A 110  ALA A 111                    
SITE     4 AC1 15 ASP A 112  SER A 154  HOH A 808                               
SITE     1 AC2 16 VAL A  30  TYR A  35  ALA A  51  LEU A  75                    
SITE     2 AC2 16 ILE A  84  LEU A 104  THR A 106  HIS A 107                    
SITE     3 AC2 16 LEU A 108  MET A 109  GLY A 110  ALA A 111                    
SITE     4 AC2 16 ASP A 112  SER A 154  HOH A 808  HOH A 821                    
SITE     1 AC3 12 TYR A  69  TYR A 182  ARG A 220  THR A 221                    
SITE     2 AC3 12 SER A 326  PHE A 327  ARG A 330  LEU A 340                    
SITE     3 AC3 12 HOH A 531  HOH A 547  HOH A 581  HOH A 602                    
SITE     1 AC4  5 ASP A 125  HIS A 126  PHE A 129  HOH A 561                    
SITE     2 AC4  5 HOH A 867                                                     
CRYST1   44.722   88.225  121.456  90.00  90.00  90.00 P 21 21 21    4          
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      0.022360  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.011335  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.008233        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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