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Database: PDB
Entry: 3R4O
LinkDB: 3R4O
Original site: 3R4O 
HEADER    CHAPERONE/CHAPERONE INHIBITOR           17-MAR-11   3R4O              
TITLE     OPTIMIZATION OF POTENT, SELECTIVE, AND ORALLY BIOAVAILABLE            
TITLE    2 PYRROLODINOPYRIMIDINE-CONTAINING INHIBITORS OF HEAT SHOCK PROTEIN 90.
TITLE    3 IDENTIFICATION OF DEVELOPMENT CANDIDATE 2-AMINO-4-{4-CHLORO-2-[2-(4- 
TITLE    4 FLUORO-1H-PYRAZOL-1-YL)ETHOXY]-6-METHYLPHENYL}-N-(2,2-               
TITLE    5 DIFLUOROPROPYL)-5,7-DIHYDRO-6H-PYRROLO[3,4-D]PYRIMIDINE-6-CARBOXAMIDE
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: HEAT SHOCK PROTEIN HSP 90-ALPHA;                           
COMPND   3 CHAIN: A, B;                                                         
COMPND   4 FRAGMENT: UNP RESIDUES 9-225;                                        
COMPND   5 SYNONYM: HEAT SHOCK 86 KDA, HSP 86, HSP86, RENAL CARCINOMA ANTIGEN   
COMPND   6 NY-REN-38;                                                           
COMPND   7 ENGINEERED: YES                                                      
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 GENE: HSP90AA1, HSP90A, HSPC1, HSPCA;                                
SOURCE   6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;                                 
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 562                                         
KEYWDS    CHAPERONE, ATP BINDING, CHAPERONE-CHAPERONE INHIBITOR COMPLEX         
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    K.S.GAJIWALA                                                          
REVDAT   2   11-APR-12 3R4O    1       JRNL   VERSN                             
REVDAT   1   27-APR-11 3R4O    0                                                
JRNL        AUTH   L.ZEHNDER,M.BENNETT,J.MENG,B.HUANG,S.NINKOVIC,F.WANG,        
JRNL        AUTH 2 J.BRAGANZA,J.TATLOCK,T.JEWELL,J.Z.ZHOU,B.BURKE,J.WANG,       
JRNL        AUTH 3 K.MAEGLEY,P.P.MEHTA,M.J.YIN,K.S.GAJIWALA,M.J.HICKEY,         
JRNL        AUTH 4 S.YAMAZAKI,E.SMITH,P.KANG,A.SISTLA,E.DOVALSANTOS,            
JRNL        AUTH 5 M.R.GEHRING,R.KANIA,M.WYTHES,P.P.KUNG                        
JRNL        TITL   OPTIMIZATION OF POTENT, SELECTIVE, AND ORALLY BIOAVAILABLE   
JRNL        TITL 2 PYRROLODINOPYRIMIDINE-CONTAINING INHIBITORS OF HEAT SHOCK    
JRNL        TITL 3 PROTEIN 90. IDENTIFICATION OF DEVELOPMENT CANDIDATE          
JRNL        TITL 4 2-AMINO-4-{4-CHLORO-2-[2-(4-FLUORO-1H-PYRAZOL-1-YL)ETHOXY]-  
JRNL        TITL 5 6-METHYLPHENYL}-N-(2,2-DIFLUOROPROPYL)-5,7-DIHYDRO-6H-       
JRNL        TITL 6 PYRROLO[3,4-D]PYRIMIDINE-6-CARBOXAMIDE.                      
JRNL        REF    J.MED.CHEM.                   V.  54  3368 2011              
JRNL        REFN                   ISSN 0022-2623                               
JRNL        PMID   21438541                                                     
JRNL        DOI    10.1021/JM200128M                                            
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.65 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : CNX 2005                                             
REMARK   3   AUTHORS     : BRUNGER,ADAMS,CLORE,DELANO,GROS,GROSSE-              
REMARK   3               : KUNSTLEVE,JIANG,KUSZEWSKI,NILGES,PANNU,              
REMARK   3               : READ,RICE,SIMONSON,WARREN,ACCELRYS                   
REMARK   3               : SOFTWARE INC.(BADGER,BERARD,KUMAR,SZALMA,            
REMARK   3               : YIP,DZAKULA)                                         
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 2.65                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 19.88                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 0.000                          
REMARK   3   DATA CUTOFF HIGH         (ABS(F)) : 228831.210                     
REMARK   3   DATA CUTOFF LOW          (ABS(F)) : 0.0000                         
REMARK   3   COMPLETENESS (WORKING+TEST)   (%) : 86.2                           
REMARK   3   NUMBER OF REFLECTIONS             : 11752                          
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) : 0.215                           
REMARK   3   R VALUE            (WORKING SET) : 0.211                           
REMARK   3   FREE R VALUE                     : 0.285                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 4.700                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 554                             
REMARK   3   ESTIMATED ERROR OF FREE R VALUE  : 0.012                           
REMARK   3                                                                      
REMARK   3  FIT/AGREEMENT OF MODEL WITH ALL DATA.                               
REMARK   3   R VALUE     (WORKING + TEST SET, NO CUTOFF) : 0.2390               
REMARK   3   R VALUE            (WORKING SET, NO CUTOFF) : 0.2350               
REMARK   3   FREE R VALUE                    (NO CUTOFF) : 0.308                
REMARK   3   FREE R VALUE TEST SET SIZE   (%, NO CUTOFF) : 4.700                
REMARK   3   FREE R VALUE TEST SET COUNT     (NO CUTOFF) : 643                  
REMARK   3   ESTIMATED ERROR OF FREE R VALUE (NO CUTOFF) : 0.0120               
REMARK   3   TOTAL NUMBER OF REFLECTIONS     (NO CUTOFF) : 13577                
REMARK   3                                                                      
REMARK   3  FIT IN THE HIGHEST RESOLUTION BIN.                                  
REMARK   3   TOTAL NUMBER OF BINS USED           : 6                            
REMARK   3   BIN RESOLUTION RANGE HIGH       (A) : 2.65                         
REMARK   3   BIN RESOLUTION RANGE LOW        (A) : 2.82                         
REMARK   3   BIN COMPLETENESS (WORKING+TEST) (%) : 75.00                        
REMARK   3   REFLECTIONS IN BIN    (WORKING SET) : 1581                         
REMARK   3   BIN R VALUE           (WORKING SET) : 0.2840                       
REMARK   3   BIN FREE R VALUE                    : 0.3950                       
REMARK   3   BIN FREE R VALUE TEST SET SIZE  (%) : 5.10                         
REMARK   3   BIN FREE R VALUE TEST SET COUNT     : 85                           
REMARK   3   ESTIMATED ERROR OF BIN FREE R VALUE : 0.043                        
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 3304                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 66                                      
REMARK   3   SOLVENT ATOMS            : 48                                      
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 31.30                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 20.30                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : -2.32000                                             
REMARK   3    B22 (A**2) : 0.21000                                              
REMARK   3    B33 (A**2) : 2.11000                                              
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) : 0.31                            
REMARK   3   ESD FROM SIGMAA              (A) : 0.31                            
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) : 0.46                            
REMARK   3   ESD FROM C-V SIGMAA          (A) : 0.46                            
REMARK   3                                                                      
REMARK   3  RMS DEVIATIONS FROM IDEAL VALUES.                                   
REMARK   3   BOND LENGTHS                 (A) : 0.006                           
REMARK   3   BOND ANGLES            (DEGREES) : 0.90                            
REMARK   3   DIHEDRAL ANGLES        (DEGREES) : 21.50                           
REMARK   3   IMPROPER ANGLES        (DEGREES) : 0.64                            
REMARK   3                                                                      
REMARK   3  ISOTROPIC THERMAL MODEL : RESTRAINED                                
REMARK   3                                                                      
REMARK   3  ISOTROPIC THERMAL FACTOR RESTRAINTS.    RMS    SIGMA                
REMARK   3   MAIN-CHAIN BOND              (A**2) : 1.270 ; 1.500                
REMARK   3   MAIN-CHAIN ANGLE             (A**2) : 2.110 ; 2.000                
REMARK   3   SIDE-CHAIN BOND              (A**2) : 1.890 ; 2.000                
REMARK   3   SIDE-CHAIN ANGLE             (A**2) : 2.860 ; 2.500                
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELING.                                              
REMARK   3   METHOD USED : FLAT MODEL                                           
REMARK   3   KSOL        : 0.35                                                 
REMARK   3   BSOL        : 20.16                                                
REMARK   3                                                                      
REMARK   3  NCS MODEL : NONE                                                    
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  : PROTEIN_REP.PARA                               
REMARK   3  PARAMETER FILE  2  : DNA-RNA_REP.PARA                               
REMARK   3  PARAMETER FILE  3  : WATER_REP.PARAM                                
REMARK   3  PARAMETER FILE  4  : ION.PARAM                                      
REMARK   3  PARAMETER FILE  5  : LIG.PARAM                                      
REMARK   3  TOPOLOGY FILE  1   : PROTEIN.TOP                                    
REMARK   3  TOPOLOGY FILE  2   : DNA-RNA.TOP                                    
REMARK   3  TOPOLOGY FILE  3   : WATER.TOP                                      
REMARK   3  TOPOLOGY FILE  4   : ION.TOP                                        
REMARK   3  TOPOLOGY FILE  5   : LIG.TOP                                        
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: NULL                                      
REMARK   4                                                                      
REMARK   4 3R4O COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 22-MAR-11.                  
REMARK 100 THE RCSB ID CODE IS RCSB064484.                                      
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 15-APR-07                          
REMARK 200  TEMPERATURE           (KELVIN) : 98                                 
REMARK 200  PH                             : 4.5                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : N                                  
REMARK 200  RADIATION SOURCE               : ROTATING ANODE                     
REMARK 200  BEAMLINE                       : NULL                               
REMARK 200  X-RAY GENERATOR MODEL          : RIGAKU                             
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.5418                             
REMARK 200  MONOCHROMATOR                  : MIRRORS                            
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : IMAGE PLATE                        
REMARK 200  DETECTOR MANUFACTURER          : MAR SCANNER 345 MM PLATE           
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : HKL-2000                           
REMARK 200  DATA SCALING SOFTWARE          : SCALEPACK                          
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 11758                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.650                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 19.880                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : 0.000                              
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 86.2                               
REMARK 200  DATA REDUNDANCY                : 4.700                              
REMARK 200  R MERGE                    (I) : 0.07400                            
REMARK 200  R SYM                      (I) : 0.07400                            
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 18.4000                            
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.65                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 2.74                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 79.6                               
REMARK 200  DATA REDUNDANCY IN SHELL       : 4.30                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.21100                            
REMARK 200  R SYM FOR SHELL            (I) : 0.21100                            
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 6.450                              
REMARK 200                                                                      
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH                              
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT        
REMARK 200 SOFTWARE USED: CNX                                                   
REMARK 200 STARTING MODEL: NULL                                                 
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 43.61                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.18                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 5 % ETHYLENE GLYCOL, 0.1 M PHOSPHATE-    
REMARK 280  CITRATE, PH 4.5, 20 MM TCEP, VAPOR DIFFUSION, HANGING DROP,         
REMARK 280  TEMPERATURE 286K                                                    
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       21.57450            
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000       65.05050            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       39.76150            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000       65.05050            
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000       21.57450            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       39.76150            
REMARK 290   SMTRY3   4  0.000000  0.000000 -1.000000        0.00000            
REMARK 290                                                                      
REMARK 290 REMARK: NULL                                                         
REMARK 300                                                                      
REMARK 300 BIOMOLECULE: 1, 2, 3                                                 
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 350                                                                      
REMARK 350 BIOMOLECULE: 2                                                       
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC                         
REMARK 350 APPLY THE FOLLOWING TO CHAINS: B                                     
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: 3                                                       
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC                    
REMARK 350 SOFTWARE USED: PISA                                                  
REMARK 350 TOTAL BURIED SURFACE AREA: 2090 ANGSTROM**2                          
REMARK 350 SURFACE AREA OF THE COMPLEX: 18460 ANGSTROM**2                       
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -14.0 KCAL/MOL                        
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, B                                  
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     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     GLU A    16                                                      
REMARK 465     GLU A   227                                                      
REMARK 465     HIS A   228                                                      
REMARK 465     HIS A   229                                                      
REMARK 465     HIS A   230                                                      
REMARK 465     HIS A   231                                                      
REMARK 465     HIS A   232                                                      
REMARK 465     HIS A   233                                                      
REMARK 465     MET B     8                                                      
REMARK 465     ASP B     9                                                      
REMARK 465     GLN B    10                                                      
REMARK 465     PRO B    11                                                      
REMARK 465     MET B    12                                                      
REMARK 465     GLU B    13                                                      
REMARK 465     GLU B    14                                                      
REMARK 465     GLU B    15                                                      
REMARK 465     GLU B    16                                                      
REMARK 465     GLU B   227                                                      
REMARK 465     HIS B   228                                                      
REMARK 465     HIS B   229                                                      
REMARK 465     HIS B   230                                                      
REMARK 465     HIS B   231                                                      
REMARK 465     HIS B   232                                                      
REMARK 465     HIS B   233                                                      
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    ASN A  40       41.07   -155.08                                   
REMARK 500    THR A  94       40.44    -93.97                                   
REMARK 500    ALA A 166     -150.31     71.26                                   
REMARK 500    ASN B  40       49.01    -76.19                                   
REMARK 500    ASP B  66       69.16   -173.30                                   
REMARK 500    ALA B 166     -151.26     78.50                                   
REMARK 500    LYS B 224       40.94    -66.80                                   
REMARK 500    GLU B 225      109.18    -21.39                                   
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: NON-CIS, NON-TRANS                                         
REMARK 500                                                                      
REMARK 500 THE FOLLOWING PEPTIDE BONDS DEVIATE SIGNIFICANTLY FROM BOTH          
REMARK 500 CIS AND TRANS CONFORMATION.  CIS BONDS, IF ANY, ARE LISTED           
REMARK 500 ON CISPEP RECORDS.  TRANS IS DEFINED AS 180 +/- 30 AND               
REMARK 500 CIS IS DEFINED AS 0 +/- 30 DEGREES.                                  
REMARK 500                                 MODEL     OMEGA                      
REMARK 500 SER A   39     ASN A   40                 -138.89                    
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 FU3 A 901                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE FU3 B 901                 
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 3R4M   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 3R4N   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 3R4P   RELATED DB: PDB                                   
DBREF  3R4O A    9   225  UNP    P07900   HS90A_HUMAN      9    225             
DBREF  3R4O B    9   225  UNP    P07900   HS90A_HUMAN      9    225             
SEQADV 3R4O MET A    8  UNP  P07900              INITIATING METHIONINE          
SEQADV 3R4O LEU A  226  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O GLU A  227  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O HIS A  228  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O HIS A  229  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O HIS A  230  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O HIS A  231  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O HIS A  232  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O HIS A  233  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O MET B    8  UNP  P07900              INITIATING METHIONINE          
SEQADV 3R4O LEU B  226  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O GLU B  227  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O HIS B  228  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O HIS B  229  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O HIS B  230  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O HIS B  231  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O HIS B  232  UNP  P07900              EXPRESSION TAG                 
SEQADV 3R4O HIS B  233  UNP  P07900              EXPRESSION TAG                 
SEQRES   1 A  226  MET ASP GLN PRO MET GLU GLU GLU GLU VAL GLU THR PHE          
SEQRES   2 A  226  ALA PHE GLN ALA GLU ILE ALA GLN LEU MET SER LEU ILE          
SEQRES   3 A  226  ILE ASN THR PHE TYR SER ASN LYS GLU ILE PHE LEU ARG          
SEQRES   4 A  226  GLU LEU ILE SER ASN SER SER ASP ALA LEU ASP LYS ILE          
SEQRES   5 A  226  ARG TYR GLU SER LEU THR ASP PRO SER LYS LEU ASP SER          
SEQRES   6 A  226  GLY LYS GLU LEU HIS ILE ASN LEU ILE PRO ASN LYS GLN          
SEQRES   7 A  226  ASP ARG THR LEU THR ILE VAL ASP THR GLY ILE GLY MET          
SEQRES   8 A  226  THR LYS ALA ASP LEU ILE ASN ASN LEU GLY THR ILE ALA          
SEQRES   9 A  226  LYS SER GLY THR LYS ALA PHE MET GLU ALA LEU GLN ALA          
SEQRES  10 A  226  GLY ALA ASP ILE SER MET ILE GLY GLN PHE GLY VAL GLY          
SEQRES  11 A  226  PHE TYR SER ALA TYR LEU VAL ALA GLU LYS VAL THR VAL          
SEQRES  12 A  226  ILE THR LYS HIS ASN ASP ASP GLU GLN TYR ALA TRP GLU          
SEQRES  13 A  226  SER SER ALA GLY GLY SER PHE THR VAL ARG THR ASP THR          
SEQRES  14 A  226  GLY GLU PRO MET GLY ARG GLY THR LYS VAL ILE LEU HIS          
SEQRES  15 A  226  LEU LYS GLU ASP GLN THR GLU TYR LEU GLU GLU ARG ARG          
SEQRES  16 A  226  ILE LYS GLU ILE VAL LYS LYS HIS SER GLN PHE ILE GLY          
SEQRES  17 A  226  TYR PRO ILE THR LEU PHE VAL GLU LYS GLU LEU GLU HIS          
SEQRES  18 A  226  HIS HIS HIS HIS HIS                                          
SEQRES   1 B  226  MET ASP GLN PRO MET GLU GLU GLU GLU VAL GLU THR PHE          
SEQRES   2 B  226  ALA PHE GLN ALA GLU ILE ALA GLN LEU MET SER LEU ILE          
SEQRES   3 B  226  ILE ASN THR PHE TYR SER ASN LYS GLU ILE PHE LEU ARG          
SEQRES   4 B  226  GLU LEU ILE SER ASN SER SER ASP ALA LEU ASP LYS ILE          
SEQRES   5 B  226  ARG TYR GLU SER LEU THR ASP PRO SER LYS LEU ASP SER          
SEQRES   6 B  226  GLY LYS GLU LEU HIS ILE ASN LEU ILE PRO ASN LYS GLN          
SEQRES   7 B  226  ASP ARG THR LEU THR ILE VAL ASP THR GLY ILE GLY MET          
SEQRES   8 B  226  THR LYS ALA ASP LEU ILE ASN ASN LEU GLY THR ILE ALA          
SEQRES   9 B  226  LYS SER GLY THR LYS ALA PHE MET GLU ALA LEU GLN ALA          
SEQRES  10 B  226  GLY ALA ASP ILE SER MET ILE GLY GLN PHE GLY VAL GLY          
SEQRES  11 B  226  PHE TYR SER ALA TYR LEU VAL ALA GLU LYS VAL THR VAL          
SEQRES  12 B  226  ILE THR LYS HIS ASN ASP ASP GLU GLN TYR ALA TRP GLU          
SEQRES  13 B  226  SER SER ALA GLY GLY SER PHE THR VAL ARG THR ASP THR          
SEQRES  14 B  226  GLY GLU PRO MET GLY ARG GLY THR LYS VAL ILE LEU HIS          
SEQRES  15 B  226  LEU LYS GLU ASP GLN THR GLU TYR LEU GLU GLU ARG ARG          
SEQRES  16 B  226  ILE LYS GLU ILE VAL LYS LYS HIS SER GLN PHE ILE GLY          
SEQRES  17 B  226  TYR PRO ILE THR LEU PHE VAL GLU LYS GLU LEU GLU HIS          
SEQRES  18 B  226  HIS HIS HIS HIS HIS                                          
HET    FU3  A 901      33                                                       
HET    FU3  B 901      33                                                       
HETNAM     FU3 2-AMINO-N-CYCLOBUTYL-4-[2,4-DICHLORO-6-(4,4,4-                   
HETNAM   2 FU3  TRIFLUOROBUTOXY)PHENYL]-5,7-DIHYDRO-6H-PYRROLO[3,4-             
HETNAM   3 FU3  D]PYRIMIDINE-6-CARBOXAMIDE                                      
FORMUL   3  FU3    2(C21 H22 CL2 F3 N5 O2)                                      
FORMUL   5  HOH   *48(H2 O)                                                     
HELIX    1   1 GLN A   23  THR A   36  1                                  14    
HELIX    2   2 GLU A   42  LEU A   64  1                                  23    
HELIX    3   3 THR A   65  ASP A   71  5                                   7    
HELIX    4   4 THR A   99  LEU A  107  1                                   9    
HELIX    5   5 GLY A  114  GLY A  125  1                                  12    
HELIX    6   6 ASP A  127  GLY A  135  5                                   9    
HELIX    7   7 VAL A  136  LEU A  143  5                                   8    
HELIX    8   8 GLU A  192  LEU A  198  5                                   7    
HELIX    9   9 GLU A  199  SER A  211  1                                  13    
HELIX   10  10 GLN B   23  THR B   36  1                                  14    
HELIX   11  11 GLU B   42  SER B   63  1                                  22    
HELIX   12  12 LEU B   64  ASP B   71  5                                   8    
HELIX   13  13 THR B   99  LEU B  107  1                                   9    
HELIX   14  14 GLY B  114  ALA B  124  1                                  11    
HELIX   15  15 ASP B  127  PHE B  134  5                                   8    
HELIX   16  16 VAL B  136  LEU B  143  5                                   8    
HELIX   17  17 GLU B  192  LEU B  198  5                                   7    
HELIX   18  18 GLU B  199  SER B  211  1                                  13    
SHEET    1   A16 GLU A  18  ALA A  21  0                                        
SHEET    2   A16 SER A 169  THR A 174 -1  O  PHE A 170   N  PHE A  20           
SHEET    3   A16 TYR A 160  SER A 164 -1  N  ALA A 161   O  ARG A 173           
SHEET    4   A16 ALA A 145  LYS A 153 -1  N  VAL A 150   O  TRP A 162           
SHEET    5   A16 GLY A 183  LEU A 190 -1  O  ILE A 187   N  THR A 149           
SHEET    6   A16 THR A  88  ASP A  93 -1  N  LEU A  89   O  LEU A 188           
SHEET    7   A16 ILE A  78  ASN A  83 -1  N  ASN A  83   O  THR A  88           
SHEET    8   A16 ILE A 218  GLU A 225  1  O  PHE A 221   N  LEU A  80           
SHEET    9   A16 ILE B 218  GLU B 223 -1  O  LEU B 220   N  LYS A 224           
SHEET   10   A16 ILE B  78  ASN B  83  1  N  LEU B  80   O  THR B 219           
SHEET   11   A16 THR B  88  ASP B  93 -1  O  VAL B  92   N  ASN B  79           
SHEET   12   A16 GLY B 183  LEU B 190 -1  O  LEU B 188   N  LEU B  89           
SHEET   13   A16 ALA B 145  LYS B 153 -1  N  ILE B 151   O  LYS B 185           
SHEET   14   A16 GLN B 159  SER B 164 -1  O  TRP B 162   N  VAL B 150           
SHEET   15   A16 SER B 169  THR B 174 -1  O  THR B 171   N  GLU B 163           
SHEET   16   A16 GLU B  18  ALA B  21 -1  N  PHE B  20   O  PHE B 170           
SITE     1 AC1 16 ASN A  51  SER A  52  ASP A  54  ALA A  55                    
SITE     2 AC1 16 LYS A  58  ASP A  93  GLY A  97  MET A  98                    
SITE     3 AC1 16 ASP A 102  ASN A 106  LEU A 107  LYS A 112                    
SITE     4 AC1 16 PHE A 138  THR A 184  HOH A 256  HOH A 259                    
SITE     1 AC2 15 ASN B  51  SER B  52  ASP B  54  ALA B  55                    
SITE     2 AC2 15 LYS B  58  ASP B  93  GLY B  97  MET B  98                    
SITE     3 AC2 15 ASP B 102  ASN B 106  LEU B 107  GLU B 120                    
SITE     4 AC2 15 PHE B 138  THR B 184  HOH B 240                               
CRYST1   43.149   79.523  130.101  90.00  90.00  90.00 P 21 21 21    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      0.023176  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.012575  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.007686        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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