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Database: PDB
Entry: 5M4H
LinkDB: 5M4H
Original site: 5M4H 
HEADER    SIGNALING PROTEIN                       18-OCT-16   5M4H              
TITLE     APPLICATION OF OFF-RATE SCREENING IN THE IDENTIFICATION OF NOVEL PAN- 
TITLE    2 ISOFORM INHIBITORS OF PYRUVATE DEHYDROGENASE KINASE                  
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: HEAT SHOCK PROTEIN HSP 90-ALPHA;                           
COMPND   3 CHAIN: A;                                                            
COMPND   4 SYNONYM: HEAT SHOCK 86 KDA,HSP86,LIPOPOLYSACCHARIDE-ASSOCIATED       
COMPND   5 PROTEIN 2,LPS-ASSOCIATED PROTEIN 2,RENAL CARCINOMA ANTIGEN NY-REN-38;
COMPND   6 ENGINEERED: YES                                                      
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 ORGAN: SKIN;                                                         
SOURCE   6 TISSUE: MELANOMA;                                                    
SOURCE   7 GENE: HSP90AA1, HSP90A, HSPC1, HSPCA;                                
SOURCE   8 EXPRESSION_SYSTEM: ESCHERICHIA COLI;                                 
SOURCE   9 EXPRESSION_SYSTEM_TAXID: 469008;                                     
SOURCE  10 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);                                 
SOURCE  11 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;                              
SOURCE  12 EXPRESSION_SYSTEM_PLASMID: PET19                                     
KEYWDS    OFF-RATE SCREENING, PDHK, HSP90, SPR, KINASE INHIBITORS, FRAGMENT     
KEYWDS   2 SCREENING, CANCER, PDK1, PDK2, PDK3, PDK4, SIGNALING PROTEIN         
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    L.M.BAKER,P.BROUGH,A.SURGENOR                                         
REVDAT   3   07-MAR-18 5M4H    1       REMARK                                   
REVDAT   2   05-APR-17 5M4H    1       JRNL                                     
REVDAT   1   22-FEB-17 5M4H    0                                                
JRNL        AUTH   P.A.BROUGH,L.BAKER,S.BEDFORD,K.BROWN,S.CHAVDA,V.CHELL,       
JRNL        AUTH 2 J.D'ALESSANDRO,N.G.DAVIES,B.DAVIS,L.LE STRAT,A.T.MACIAS,     
JRNL        AUTH 3 D.MADDOX,P.C.MAHON,A.J.MASSEY,N.MATASSOVA,S.MCKENNA,         
JRNL        AUTH 4 J.W.MEISSNER,J.D.MOORE,J.B.MURRAY,C.J.NORTHFIELD,C.PARRY,    
JRNL        AUTH 5 R.PARSONS,S.D.ROUGHLEY,T.SHAW,H.SIMMONITE,S.STOKES,          
JRNL        AUTH 6 A.SURGENOR,E.STEFANIAK,A.ROBERTSON,Y.WANG,P.WEBB,            
JRNL        AUTH 7 N.WHITEHEAD,M.WOOD                                           
JRNL        TITL   APPLICATION OF OFF-RATE SCREENING IN THE IDENTIFICATION OF   
JRNL        TITL 2 NOVEL PAN-ISOFORM INHIBITORS OF PYRUVATE DEHYDROGENASE       
JRNL        TITL 3 KINASE.                                                      
JRNL        REF    J. MED. CHEM.                 V.  60  2271 2017              
JRNL        REFN                   ISSN 1520-4804                               
JRNL        PMID   28199108                                                     
JRNL        DOI    10.1021/ACS.JMEDCHEM.6B01478                                 
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.00 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : REFMAC 5.8.0135                                      
REMARK   3   AUTHORS     : MURSHUDOV,VAGIN,DODSON                               
REMARK   3                                                                      
REMARK   3    REFINEMENT TARGET : NULL                                          
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 2.00                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 64.57                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : NULL                           
REMARK   3   COMPLETENESS FOR RANGE        (%) : 92.3                           
REMARK   3   NUMBER OF REFLECTIONS             : 16318                          
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 + TEST SET) : 0.228                           
REMARK   3   R VALUE            (WORKING SET) : 0.224                           
REMARK   3   FREE R VALUE                     : 0.317                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 4.800                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 815                             
REMARK   3                                                                      
REMARK   3  FIT IN THE HIGHEST RESOLUTION BIN.                                  
REMARK   3   TOTAL NUMBER OF BINS USED           : 20                           
REMARK   3   BIN RESOLUTION RANGE HIGH       (A) : 2.00                         
REMARK   3   BIN RESOLUTION RANGE LOW        (A) : 2.05                         
REMARK   3   REFLECTION IN BIN     (WORKING SET) : 1182                         
REMARK   3   BIN COMPLETENESS (WORKING+TEST) (%) : 94.05                        
REMARK   3   BIN R VALUE           (WORKING SET) : 0.4150                       
REMARK   3   BIN FREE R VALUE SET COUNT          : 66                           
REMARK   3   BIN FREE R VALUE                    : 0.5420                       
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 1616                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 28                                      
REMARK   3   SOLVENT ATOMS            : 271                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : NULL                           
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 27.30                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : -1.02000                                             
REMARK   3    B22 (A**2) : 0.71000                                              
REMARK   3    B33 (A**2) : 0.30000                                              
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 OVERALL COORDINATE ERROR.                                 
REMARK   3   ESU BASED ON R VALUE                            (A): 0.221         
REMARK   3   ESU BASED ON FREE R VALUE                       (A): 0.227         
REMARK   3   ESU BASED ON MAXIMUM LIKELIHOOD                 (A): 0.180         
REMARK   3   ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 7.026         
REMARK   3                                                                      
REMARK   3 CORRELATION COEFFICIENTS.                                            
REMARK   3   CORRELATION COEFFICIENT FO-FC      : 0.934                         
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.857                         
REMARK   3                                                                      
REMARK   3  RMS DEVIATIONS FROM IDEAL VALUES        COUNT    RMS    WEIGHT      
REMARK   3   BOND LENGTHS REFINED ATOMS        (A):  1681 ; 0.020 ; 0.020       
REMARK   3   BOND LENGTHS OTHERS               (A):  1602 ; 0.003 ; 0.020       
REMARK   3   BOND ANGLES REFINED ATOMS   (DEGREES):  2276 ; 1.919 ; 1.984       
REMARK   3   BOND ANGLES OTHERS          (DEGREES):  3690 ; 1.036 ; 3.002       
REMARK   3   TORSION ANGLES, PERIOD 1    (DEGREES):   209 ; 6.714 ; 5.000       
REMARK   3   TORSION ANGLES, PERIOD 2    (DEGREES):    72 ;36.771 ;24.722       
REMARK   3   TORSION ANGLES, PERIOD 3    (DEGREES):   300 ;16.364 ;15.000       
REMARK   3   TORSION ANGLES, PERIOD 4    (DEGREES):     8 ;26.240 ;15.000       
REMARK   3   CHIRAL-CENTER RESTRAINTS       (A**3):   260 ; 0.100 ; 0.200       
REMARK   3   GENERAL PLANES REFINED ATOMS      (A):  1882 ; 0.008 ; 0.020       
REMARK   3   GENERAL PLANES OTHERS             (A):   369 ; 0.002 ; 0.020       
REMARK   3   NON-BONDED CONTACTS REFINED ATOMS (A):  NULL ;  NULL ;  NULL       
REMARK   3   NON-BONDED CONTACTS OTHERS        (A):  NULL ;  NULL ;  NULL       
REMARK   3   NON-BONDED TORSION REFINED ATOMS  (A):  NULL ;  NULL ;  NULL       
REMARK   3   NON-BONDED TORSION OTHERS         (A):  NULL ;  NULL ;  NULL       
REMARK   3   H-BOND (X...Y) REFINED ATOMS      (A):  NULL ;  NULL ;  NULL       
REMARK   3   H-BOND (X...Y) OTHERS             (A):  NULL ;  NULL ;  NULL       
REMARK   3   POTENTIAL METAL-ION REFINED ATOMS (A):  NULL ;  NULL ;  NULL       
REMARK   3   POTENTIAL METAL-ION OTHERS        (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY VDW REFINED ATOMS        (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY VDW OTHERS               (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY H-BOND REFINED ATOMS     (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY H-BOND OTHERS            (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY METAL-ION REFINED ATOMS  (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY METAL-ION OTHERS         (A):  NULL ;  NULL ;  NULL       
REMARK   3                                                                      
REMARK   3  ISOTROPIC THERMAL FACTOR RESTRAINTS.     COUNT   RMS    WEIGHT      
REMARK   3   MAIN-CHAIN BOND REFINED ATOMS  (A**2):   833 ; 2.288 ; 2.571       
REMARK   3   MAIN-CHAIN BOND OTHER ATOMS    (A**2):   832 ; 2.274 ; 2.569       
REMARK   3   MAIN-CHAIN ANGLE REFINED ATOMS (A**2):  1040 ; 3.425 ; 3.851       
REMARK   3   MAIN-CHAIN ANGLE OTHER ATOMS   (A**2):  1041 ; 3.425 ; 3.852       
REMARK   3   SIDE-CHAIN BOND REFINED ATOMS  (A**2):   848 ; 2.828 ; 2.812       
REMARK   3   SIDE-CHAIN BOND OTHER ATOMS    (A**2):   843 ; 2.804 ; 2.793       
REMARK   3   SIDE-CHAIN ANGLE REFINED ATOMS (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SIDE-CHAIN ANGLE OTHER ATOMS   (A**2):  1230 ; 4.407 ; 4.090       
REMARK   3   LONG RANGE B REFINED ATOMS     (A**2):  8173 ; 6.998 ;24.470       
REMARK   3   LONG RANGE B OTHER ATOMS       (A**2):  7851 ; 6.773 ;24.103       
REMARK   3                                                                      
REMARK   3 ANISOTROPIC THERMAL FACTOR RESTRAINTS.    COUNT   RMS   WEIGHT       
REMARK   3   RIGID-BOND RESTRAINTS          (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SPHERICITY; FREE ATOMS         (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SPHERICITY; BONDED ATOMS       (A**2):  NULL ;  NULL ;  NULL       
REMARK   3                                                                      
REMARK   3  NCS RESTRAINTS STATISTICS                                           
REMARK   3   NUMBER OF DIFFERENT NCS GROUPS : NULL                              
REMARK   3                                                                      
REMARK   3  TLS DETAILS                                                         
REMARK   3   NUMBER OF TLS GROUPS  : NULL                                       
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELLING.                                             
REMARK   3   METHOD USED : NULL                                                 
REMARK   3   PARAMETERS FOR MASK CALCULATION                                    
REMARK   3   VDW PROBE RADIUS   : 1.20                                          
REMARK   3   ION PROBE RADIUS   : 0.80                                          
REMARK   3   SHRINKAGE RADIUS   : 0.80                                          
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: HYDROGENS HAVE BEEN ADDED IN THE RIDING   
REMARK   3  POSITIONS                                                           
REMARK   4                                                                      
REMARK   4 5M4H COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 19-OCT-16.                  
REMARK 100 THE DEPOSITION ID IS D_1200001925.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 09-SEP-16                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : 6.5                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : N                                  
REMARK 200  RADIATION SOURCE               : SEALED TUBE                        
REMARK 200  BEAMLINE                       : NULL                               
REMARK 200  X-RAY GENERATOR MODEL          : BRUKER D8 QUEST                    
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.51484                            
REMARK 200  MONOCHROMATOR                  : CU FILTER                          
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : PIXEL                              
REMARK 200  DETECTOR MANUFACTURER          : BRUKER PHOTON 100                  
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : SAINT                              
REMARK 200  DATA SCALING SOFTWARE          : SADABS                             
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 17134                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.000                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 64.570                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : NULL                               
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 92.3                               
REMARK 200  DATA REDUNDANCY                : 2.900                              
REMARK 200  R MERGE                    (I) : 0.13780                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 7.8400                             
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) : 2.03                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 94.4                               
REMARK 200  DATA REDUNDANCY IN SHELL       : 2.55                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.51650                            
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 2.500                              
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: 1UYL                                                 
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 47.75                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.35                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1M NA CACODYLATE PH 6.5 25% PEG 2K     
REMARK 280  MME 0.2M MGCL2, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 277K     
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: I 2 2 2                          
REMARK 290                                                                      
REMARK 290      SYMOP   SYMMETRY                                                
REMARK 290     NNNMMM   OPERATOR                                                
REMARK 290       1555   X,Y,Z                                                   
REMARK 290       2555   -X,-Y,Z                                                 
REMARK 290       3555   -X,Y,-Z                                                 
REMARK 290       4555   X,-Y,-Z                                                 
REMARK 290       5555   X+1/2,Y+1/2,Z+1/2                                       
REMARK 290       6555   -X+1/2,-Y+1/2,Z+1/2                                     
REMARK 290       7555   -X+1/2,Y+1/2,-Z+1/2                                     
REMARK 290       8555   X+1/2,-Y+1/2,-Z+1/2                                     
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        0.00000            
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000        0.00000            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000        0.00000            
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        0.00000            
REMARK 290   SMTRY1   5  1.000000  0.000000  0.000000       32.00550            
REMARK 290   SMTRY2   5  0.000000  1.000000  0.000000       43.27600            
REMARK 290   SMTRY3   5  0.000000  0.000000  1.000000       48.47850            
REMARK 290   SMTRY1   6 -1.000000  0.000000  0.000000       32.00550            
REMARK 290   SMTRY2   6  0.000000 -1.000000  0.000000       43.27600            
REMARK 290   SMTRY3   6  0.000000  0.000000  1.000000       48.47850            
REMARK 290   SMTRY1   7 -1.000000  0.000000  0.000000       32.00550            
REMARK 290   SMTRY2   7  0.000000  1.000000  0.000000       43.27600            
REMARK 290   SMTRY3   7  0.000000  0.000000 -1.000000       48.47850            
REMARK 290   SMTRY1   8  1.000000  0.000000  0.000000       32.00550            
REMARK 290   SMTRY2   8  0.000000 -1.000000  0.000000       43.27600            
REMARK 290   SMTRY3   8  0.000000  0.000000 -1.000000       48.47850            
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 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC                  
REMARK 350 SOFTWARE USED: PISA                                                  
REMARK 350 TOTAL BURIED SURFACE AREA: 180 ANGSTROM**2                           
REMARK 350 SURFACE AREA OF THE COMPLEX: 9540 ANGSTROM**2                        
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -13.0 KCAL/MOL                        
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 375                                                                      
REMARK 375 SPECIAL POSITION                                                     
REMARK 375 THE FOLLOWING ATOMS ARE FOUND TO BE WITHIN 0.15 ANGSTROMS            
REMARK 375 OF A SYMMETRY RELATED ATOM AND ARE ASSUMED TO BE ON SPECIAL          
REMARK 375 POSITIONS.                                                           
REMARK 375                                                                      
REMARK 375 ATOM RES CSSEQI                                                      
REMARK 375      HOH A 619  LIES ON A SPECIAL POSITION.                          
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   -15                                                      
REMARK 465     GLY A   -14                                                      
REMARK 465     HIS A   -13                                                      
REMARK 465     HIS A   -12                                                      
REMARK 465     HIS A   -11                                                      
REMARK 465     HIS A   -10                                                      
REMARK 465     HIS A    -9                                                      
REMARK 465     HIS A    -8                                                      
REMARK 465     HIS A    -7                                                      
REMARK 465     HIS A    -6                                                      
REMARK 465     HIS A    -5                                                      
REMARK 465     HIS A    -4                                                      
REMARK 465     SER A    -3                                                      
REMARK 465     SER A    -2                                                      
REMARK 465     GLY A    -1                                                      
REMARK 465     HIS A     0                                                      
REMARK 465     ILE A     1                                                      
REMARK 465     ASP A     2                                                      
REMARK 465     ASP A     3                                                      
REMARK 465     ALA A     4                                                      
REMARK 465     ASP A     5                                                      
REMARK 465     LYS A     6                                                      
REMARK 465     HIS A     7                                                      
REMARK 465     MET A     8                                                      
REMARK 465     ASP A     9                                                      
REMARK 465     GLN A    10                                                      
REMARK 465     PRO A    11                                                      
REMARK 465     MET A    12                                                      
REMARK 465     GLU A    13                                                      
REMARK 465     GLU A    14                                                      
REMARK 465     GLU A    15                                                      
REMARK 465     LYS A   224                                                      
REMARK 465     GLU A   225                                                      
REMARK 465     ARG A   226                                                      
REMARK 465     ASP A   227                                                      
REMARK 465     LYS A   228                                                      
REMARK 465     GLU A   229                                                      
REMARK 465     VAL A   230                                                      
REMARK 465     SER A   231                                                      
REMARK 465     ASP A   232                                                      
REMARK 465     ASP A   233                                                      
REMARK 465     GLU A   234                                                      
REMARK 465     ALA A   235                                                      
REMARK 465     GLU A   236                                                      
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  16    CG   CD   OE1  OE2                                  
REMARK 470     GLN A  85    CG   CD   OE1  NE2                                  
REMARK 470     GLN A 123    CG   CD   OE1  NE2                                  
REMARK 470     GLU A 192    CG   CD   OE1  OE2                                  
REMARK 470     LYS A 208    CD   CE   NZ                                        
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    HOH A   473     O    HOH A   515              2.01            
REMARK 500   O    HOH A   407     O    HOH A   542              2.12            
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   O    HOH A   581     O    HOH A   594     2655     2.17            
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    ASP A 157   CB  -  CG  -  OD1 ANGL. DEV. =   7.6 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    TYR A  38      103.86   -165.57                                   
REMARK 500    THR A  94       41.11   -102.04                                   
REMARK 500    ILE A 110       58.67    -98.89                                   
REMARK 500    ALA A 124       41.47    -77.66                                   
REMARK 500    ALA A 126      154.88    -49.80                                   
REMARK 500    ALA A 166     -144.56     70.71                                   
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 525                                                                      
REMARK 525 SOLVENT                                                              
REMARK 525                                                                      
REMARK 525 THE SOLVENT MOLECULES HAVE CHAIN IDENTIFIERS THAT                    
REMARK 525 INDICATE THE POLYMER CHAIN WITH WHICH THEY ARE MOST                  
REMARK 525 CLOSELY ASSOCIATED. THE REMARK LISTS ALL THE SOLVENT                 
REMARK 525 MOLECULES WHICH ARE MORE THAN 5A AWAY FROM THE                       
REMARK 525 NEAREST POLYMER CHAIN (M = MODEL NUMBER;                             
REMARK 525 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE                  
REMARK 525 NUMBER; I=INSERTION CODE):                                           
REMARK 525                                                                      
REMARK 525  M RES CSSEQI                                                        
REMARK 525    HOH A 671        DISTANCE =  6.13 ANGSTROMS                       
REMARK 800                                                                      
REMARK 800 SITE                                                                 
REMARK 800 SITE_IDENTIFIER: AC1                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue 7FX A 301                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 302                 
DBREF  5M4H A    9   236  UNP    P07900   HS90A_HUMAN      9    236             
SEQADV 5M4H MET A  -15  UNP  P07900              INITIATING METHIONINE          
SEQADV 5M4H GLY A  -14  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H HIS A  -13  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H HIS A  -12  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H HIS A  -11  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H HIS A  -10  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H HIS A   -9  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H HIS A   -8  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H HIS A   -7  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H HIS A   -6  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H HIS A   -5  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H HIS A   -4  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H SER A   -3  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H SER A   -2  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H GLY A   -1  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H HIS A    0  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H ILE A    1  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H ASP A    2  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H ASP A    3  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H ALA A    4  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H ASP A    5  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H LYS A    6  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H HIS A    7  UNP  P07900              EXPRESSION TAG                 
SEQADV 5M4H MET A    8  UNP  P07900              EXPRESSION TAG                 
SEQRES   1 A  252  MET GLY HIS HIS HIS HIS HIS HIS HIS HIS HIS HIS SER          
SEQRES   2 A  252  SER GLY HIS ILE ASP ASP ALA ASP LYS HIS MET ASP GLN          
SEQRES   3 A  252  PRO MET GLU GLU GLU GLU VAL GLU THR PHE ALA PHE GLN          
SEQRES   4 A  252  ALA GLU ILE ALA GLN LEU MET SER LEU ILE ILE ASN THR          
SEQRES   5 A  252  PHE TYR SER ASN LYS GLU ILE PHE LEU ARG GLU LEU ILE          
SEQRES   6 A  252  SER ASN SER SER ASP ALA LEU ASP LYS ILE ARG TYR GLU          
SEQRES   7 A  252  SER LEU THR ASP PRO SER LYS LEU ASP SER GLY LYS GLU          
SEQRES   8 A  252  LEU HIS ILE ASN LEU ILE PRO ASN LYS GLN ASP ARG THR          
SEQRES   9 A  252  LEU THR ILE VAL ASP THR GLY ILE GLY MET THR LYS ALA          
SEQRES  10 A  252  ASP LEU ILE ASN ASN LEU GLY THR ILE ALA LYS SER GLY          
SEQRES  11 A  252  THR LYS ALA PHE MET GLU ALA LEU GLN ALA GLY ALA ASP          
SEQRES  12 A  252  ILE SER MET ILE GLY GLN PHE GLY VAL GLY PHE TYR SER          
SEQRES  13 A  252  ALA TYR LEU VAL ALA GLU LYS VAL THR VAL ILE THR LYS          
SEQRES  14 A  252  HIS ASN ASP ASP GLU GLN TYR ALA TRP GLU SER SER ALA          
SEQRES  15 A  252  GLY GLY SER PHE THR VAL ARG THR ASP THR GLY GLU PRO          
SEQRES  16 A  252  MET GLY ARG GLY THR LYS VAL ILE LEU HIS LEU LYS GLU          
SEQRES  17 A  252  ASP GLN THR GLU TYR LEU GLU GLU ARG ARG ILE LYS GLU          
SEQRES  18 A  252  ILE VAL LYS LYS HIS SER GLN PHE ILE GLY TYR PRO ILE          
SEQRES  19 A  252  THR LEU PHE VAL GLU LYS GLU ARG ASP LYS GLU VAL SER          
SEQRES  20 A  252  ASP ASP GLU ALA GLU                                          
HET    7FX  A 301      23                                                       
HET    SO4  A 302       5                                                       
HETNAM     7FX [2,4-BIS(OXIDANYL)PHENYL]-[(7~{S})-7-(TRIFLUOROMETHYL)-          
HETNAM   2 7FX  6,7-DIHYDRO-5~{H}-PYRAZOLO[1,5-A]PYRIMIDIN-4-                   
HETNAM   3 7FX  YL]METHANONE                                                    
HETNAM     SO4 SULFATE ION                                                      
FORMUL   2  7FX    C14 H12 F3 N3 O3                                             
FORMUL   3  SO4    O4 S 2-                                                      
FORMUL   4  HOH   *271(H2 O)                                                    
HELIX    1 AA1 GLN A   23  THR A   36  1                                  14    
HELIX    2 AA2 GLU A   42  LEU A   64  1                                  23    
HELIX    3 AA3 THR A   65  ASP A   71  5                                   7    
HELIX    4 AA4 THR A   99  ASN A  105  1                                   7    
HELIX    5 AA5 ASN A  106  THR A  109  5                                   4    
HELIX    6 AA6 ILE A  110  ALA A  124  1                                  15    
HELIX    7 AA7 ASP A  127  GLY A  135  5                                   9    
HELIX    8 AA8 VAL A  136  LEU A  143  5                                   8    
HELIX    9 AA9 GLU A  192  LEU A  198  5                                   7    
HELIX   10 AB1 GLU A  199  SER A  211  1                                  13    
SHEET    1 AA1 8 VAL A  17  ALA A  21  0                                        
SHEET    2 AA1 8 SER A 169  THR A 174 -1  O  VAL A 172   N  GLU A  18           
SHEET    3 AA1 8 TYR A 160  SER A 164 -1  N  GLU A 163   O  THR A 171           
SHEET    4 AA1 8 ALA A 145  LYS A 153 -1  N  VAL A 148   O  SER A 164           
SHEET    5 AA1 8 GLY A 183  LEU A 190 -1  O  ILE A 187   N  THR A 149           
SHEET    6 AA1 8 THR A  88  ASP A  93 -1  N  ASP A  93   O  THR A 184           
SHEET    7 AA1 8 ILE A  78  ASN A  83 -1  N  ASN A  83   O  THR A  88           
SHEET    8 AA1 8 ILE A 218  LEU A 220  1  O  THR A 219   N  LEU A  80           
SITE     1 AC1 15 LEU A  48  ASN A  51  ALA A  55  LYS A  58                    
SITE     2 AC1 15 ASP A  93  ILE A  96  GLY A  97  MET A  98                    
SITE     3 AC1 15 GLY A 108  THR A 184  VAL A 186  HOH A 425                    
SITE     4 AC1 15 HOH A 444  HOH A 450  HOH A 464                               
SITE     1 AC2  8 THR A  19  GLU A  75  HIS A  77  ASN A  79                    
SITE     2 AC2  8 SER A 169  HOH A 411  HOH A 455  HOH A 520                    
CRYST1   64.011   86.552   96.957  90.00  90.00  90.00 I 2 2 2       8          
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      0.015622  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.011554  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.010314        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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