GenomeNet

Database: PDB
Entry: 4HXL
LinkDB: 4HXL
Original site: 4HXL 
HEADER    PROTEIN BINDING/INHIBITOR               12-NOV-12   4HXL              
TITLE     BRD4 BROMODOMAIN 1 COMPLEX WITH 3-CYCLOHEXYL-N-{3-(2-OXO-2,3-DIHYDRO- 
TITLE    2 1,3-THIAZOL-4-YL)-5-[(THIOPHEN-2-YLSULFONYL)AMINO]PHENYL}PROPANAMIDE 
TITLE    3 INHIBITOR                                                            
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: BROMODOMAIN-CONTAINING PROTEIN 4;                          
COMPND   3 CHAIN: A;                                                            
COMPND   4 SYNONYM: PROTEIN HUNK1;                                              
COMPND   5 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: BRD4, HUNK1;                                                   
SOURCE   6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;                                 
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 562;                                        
SOURCE   8 EXPRESSION_SYSTEM_STRAIN: BL21(DE3)CODON PLUS;                       
SOURCE   9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;                              
SOURCE  10 EXPRESSION_SYSTEM_PLASMID: PET28A                                    
KEYWDS    BRD4, BROMODOMAIN, FOUR ALPHA HELICES, PROTEIN BINDING-INHIBITOR      
KEYWDS   2 COMPLEX                                                              
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    T.T.CHEN,D.Y.CAO,W.Y.CHEN,B.XIONG,J.K.SHEN,Y.C.XU                     
REVDAT   4   28-FEB-24 4HXL    1       REMARK SEQADV                            
REVDAT   3   19-JUN-13 4HXL    1       JRNL                                     
REVDAT   2   10-APR-13 4HXL    1       AUTHOR                                   
REVDAT   1   03-APR-13 4HXL    0                                                
JRNL        AUTH   L.ZHAO,D.CAO,T.CHEN,Y.WANG,Z.MIAO,Y.XU,W.CHEN,X.WANG,Y.LI,   
JRNL        AUTH 2 Z.DU,B.XIONG,J.LI,C.XU,N.ZHANG,J.HE,J.SHEN                   
JRNL        TITL   FRAGMENT-BASED DRUG DISCOVERY OF 2-THIAZOLIDINONES AS        
JRNL        TITL 2 INHIBITORS OF THE HISTONE READER BRD4 BROMODOMAIN.           
JRNL        REF    J.MED.CHEM.                   V.  56  3833 2013              
JRNL        REFN                   ISSN 0022-2623                               
JRNL        PMID   23530754                                                     
JRNL        DOI    10.1021/JM301793A                                            
REMARK   2                                                                      
REMARK   2 RESOLUTION.    1.52 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : PHENIX 1.8_1069                                      
REMARK   3   AUTHORS     : PAUL ADAMS,PAVEL AFONINE,VINCENT CHEN,IAN            
REMARK   3               : DAVIS,KRESHNA GOPAL,RALF GROSSE-KUNSTLEVE,           
REMARK   3               : LI-WEI HUNG,ROBERT IMMORMINO,TOM IOERGER,            
REMARK   3               : AIRLIE MCCOY,ERIK MCKEE,NIGEL MORIARTY,              
REMARK   3               : REETAL PAI,RANDY READ,JANE RICHARDSON,               
REMARK   3               : DAVID RICHARDSON,TOD ROMO,JIM SACCHETTINI,           
REMARK   3               : NICHOLAS SAUTER,JACOB SMITH,LAURENT                  
REMARK   3               : STORONI,TOM TERWILLIGER,PETER ZWART                  
REMARK   3                                                                      
REMARK   3    REFINEMENT TARGET : MLHL                                          
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 1.52                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 30.28                          
REMARK   3   MIN(FOBS/SIGMA_FOBS)              : 2.010                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 99.1                           
REMARK   3   NUMBER OF REFLECTIONS             : 18944                          
REMARK   3                                                                      
REMARK   3  FIT TO DATA USED IN REFINEMENT.                                     
REMARK   3   R VALUE     (WORKING + TEST SET) : 0.171                           
REMARK   3   R VALUE            (WORKING SET) : 0.170                           
REMARK   3   FREE R VALUE                     : 0.191                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 3.000                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 568                             
REMARK   3                                                                      
REMARK   3  FIT TO DATA USED IN REFINEMENT (IN BINS).                           
REMARK   3   BIN  RESOLUTION RANGE  COMPL.    NWORK NFREE   RWORK  RFREE        
REMARK   3     1 30.2855 -  2.4126    0.98     4734   147  0.1739 0.1860        
REMARK   3     2  2.4126 -  1.9151    1.00     4600   142  0.1704 0.1924        
REMARK   3     3  1.9151 -  1.6730    0.99     4527   140  0.1639 0.2091        
REMARK   3     4  1.6730 -  1.5201    0.99     4515   139  0.1624 0.1930        
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELLING.                                             
REMARK   3   METHOD USED        : FLAT BULK SOLVENT MODEL                       
REMARK   3   SOLVENT RADIUS     : 1.11                                          
REMARK   3   SHRINKAGE RADIUS   : 0.90                                          
REMARK   3   K_SOL              : NULL                                          
REMARK   3   B_SOL              : NULL                                          
REMARK   3                                                                      
REMARK   3  ERROR ESTIMATES.                                                    
REMARK   3   COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED)     : 0.080            
REMARK   3   PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 18.980           
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 18.99                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 17.61                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : NULL                                                 
REMARK   3    B22 (A**2) : NULL                                                 
REMARK   3    B33 (A**2) : NULL                                                 
REMARK   3    B12 (A**2) : NULL                                                 
REMARK   3    B13 (A**2) : NULL                                                 
REMARK   3    B23 (A**2) : NULL                                                 
REMARK   3                                                                      
REMARK   3  TWINNING INFORMATION.                                               
REMARK   3   FRACTION: NULL                                                     
REMARK   3   OPERATOR: NULL                                                     
REMARK   3                                                                      
REMARK   3  DEVIATIONS FROM IDEAL VALUES.                                       
REMARK   3                 RMSD          COUNT                                  
REMARK   3   BOND      :  0.006           1107                                  
REMARK   3   ANGLE     :  1.144           1508                                  
REMARK   3   CHIRALITY :  0.074            157                                  
REMARK   3   PLANARITY :  0.005            192                                  
REMARK   3   DIHEDRAL  : 15.561            434                                  
REMARK   3                                                                      
REMARK   3  TLS DETAILS                                                         
REMARK   3   NUMBER OF TLS GROUPS  : NULL                                       
REMARK   3                                                                      
REMARK   3  NCS DETAILS                                                         
REMARK   3   NUMBER OF NCS GROUPS : NULL                                        
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: NULL                                      
REMARK   4                                                                      
REMARK   4 4HXL COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 15-NOV-12.                  
REMARK 100 THE DEPOSITION ID IS D_1000076046.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 21-OCT-12                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : NULL                               
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : SSRF                               
REMARK 200  BEAMLINE                       : BL17U                              
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 0.979                              
REMARK 200  MONOCHROMATOR                  : NULL                               
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : CCD                                
REMARK 200  DETECTOR MANUFACTURER          : ADSC QUANTUM 315R                  
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : XDS                                
REMARK 200  DATA SCALING SOFTWARE          : XSCALE                             
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : NULL                               
REMARK 200  RESOLUTION RANGE HIGH      (A) : 1.520                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 30.279                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : -3.000                             
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 99.1                               
REMARK 200  DATA REDUNDANCY                : NULL                               
REMARK 200  R MERGE                    (I) : 0.04000                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 21.4900                            
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.52                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 1.56                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 99.4                               
REMARK 200  DATA REDUNDANCY IN SHELL       : NULL                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.13200                            
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 9.420                              
REMARK 200                                                                      
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH                              
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT        
REMARK 200 SOFTWARE USED: PHASER 2.1.4                                          
REMARK 200 STARTING MODEL: NULL                                                 
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 38.74                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.01                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 3.6M NA FORMATE, 10% GLYCEROL, VAPOR     
REMARK 280  DIFFUSION, HANGING DROP, TEMPERATURE 293K                           
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       16.05000            
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000       39.52500            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       23.55500            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000       39.52500            
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000       16.05000            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       23.55500            
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 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC                  
REMARK 350 SOFTWARE USED: PISA                                                  
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 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 167    CG   CD   OE1  OE2                                  
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  52      107.29   -161.12                                   
REMARK 500    ASN A 140     -147.34   -112.56                                   
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 1A9 A 201                 
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 4HXK   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4HXM   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4HXN   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4HXO   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4HXP   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4HXR   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4HXS   RELATED DB: PDB                                   
DBREF  4HXL A   44   167  UNP    O60885   BRD4_HUMAN      44    167             
SEQADV 4HXL MET A   43  UNP  O60885              EXPRESSION TAG                 
SEQRES   1 A  125  MET ASN PRO PRO PRO PRO GLU THR SER ASN PRO ASN LYS          
SEQRES   2 A  125  PRO LYS ARG GLN THR ASN GLN LEU GLN TYR LEU LEU ARG          
SEQRES   3 A  125  VAL VAL LEU LYS THR LEU TRP LYS HIS GLN PHE ALA TRP          
SEQRES   4 A  125  PRO PHE GLN GLN PRO VAL ASP ALA VAL LYS LEU ASN LEU          
SEQRES   5 A  125  PRO ASP TYR TYR LYS ILE ILE LYS THR PRO MET ASP MET          
SEQRES   6 A  125  GLY THR ILE LYS LYS ARG LEU GLU ASN ASN TYR TYR TRP          
SEQRES   7 A  125  ASN ALA GLN GLU CYS ILE GLN ASP PHE ASN THR MET PHE          
SEQRES   8 A  125  THR ASN CYS TYR ILE TYR ASN LYS PRO GLY ASP ASP ILE          
SEQRES   9 A  125  VAL LEU MET ALA GLU ALA LEU GLU LYS LEU PHE LEU GLN          
SEQRES  10 A  125  LYS ILE ASN GLU LEU PRO THR GLU                              
HET    1A9  A 201      32                                                       
HETNAM     1A9 3-CYCLOHEXYL-N-{3-(2-OXO-2,3-DIHYDRO-1,3-THIAZOL-4-YL)-          
HETNAM   2 1A9  5-[(THIOPHEN-2-YLSULFONYL)AMINO]PHENYL}PROPANAMIDE              
FORMUL   2  1A9    C22 H25 N3 O4 S3                                             
FORMUL   3  HOH   *152(H2 O)                                                    
HELIX    1   1 THR A   60  VAL A   69  1                                  10    
HELIX    2   2 VAL A   69  TRP A   75  1                                   7    
HELIX    3   3 ALA A   80  GLN A   84  5                                   5    
HELIX    4   4 ASP A   96  ILE A  101  1                                   6    
HELIX    5   5 ASP A  106  ASN A  116  1                                  11    
HELIX    6   6 ASN A  121  ASN A  140  1                                  20    
HELIX    7   7 ASP A  144  ASN A  162  1                                  19    
SITE     1 AC1 15 TRP A  81  PRO A  82  GLN A  85  LEU A  92                    
SITE     2 AC1 15 ASN A  93  ASP A  96  LYS A  99  ILE A 100                    
SITE     3 AC1 15 ASN A 140  ILE A 146  HOH A 307  HOH A 325                    
SITE     4 AC1 15 HOH A 364  HOH A 374  HOH A 380                               
CRYST1   32.100   47.110   79.050  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      0.031153  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.021227  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.012650        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
DBGET integrated database retrieval system