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Database: PDB
Entry: 5V67
LinkDB: 5V67
Original site: 5V67 
HEADER    TRANSCRIPTION/INHIBITOR                 16-MAR-17   5V67              
TITLE     CRYSTAL STRUCTURE OF THE FIRST BROMODOMAIN OF HUMAN BRD4 IN COMPLEX   
TITLE    2 WITH VOLASERTIB                                                      
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: BROMODOMAIN-CONTAINING PROTEIN 4;                          
COMPND   3 CHAIN: A;                                                            
COMPND   4 FRAGMENT: UNP RESIDUES 44-168;                                       
COMPND   5 SYNONYM: PROTEIN HUNK1;                                              
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 GENE: BRD4, HUNK1;                                                   
SOURCE   6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;                                 
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 469008;                                     
SOURCE   8 EXPRESSION_SYSTEM_STRAIN: BL21(DE3)-R3;                              
SOURCE   9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;                              
SOURCE  10 EXPRESSION_SYSTEM_PLASMID: PNIC28-BSA4                               
KEYWDS    BROMODOMAIN, CAP, HUNK1, MCAP, PROTEIN BINDING-INHIBITOR COMPLEX,     
KEYWDS   2 MITOTIC CHROMOSOME ASSOCIATED PROTEIN, INHIBITOR, TRANSCRIPTION-     
KEYWDS   3 INHIBITOR COMPLEX                                                    
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    S.W.EMBER,J.-Y.ZHU,E.SCHONBRUNN                                       
REVDAT   5   04-OCT-23 5V67    1       REMARK                                   
REVDAT   4   17-NOV-21 5V67    1       JRNL                                     
REVDAT   3   11-DEC-19 5V67    1       COMPND HETNAM                            
REVDAT   2   11-APR-18 5V67    1       COMPND HETNAM HETSYN ATOM                
REVDAT   1   28-MAR-18 5V67    0                                                
JRNL        AUTH   R.M.KARIM,M.J.BIKOWITZ,A.CHAN,J.Y.ZHU,D.GRASSIE,A.BECKER,    
JRNL        AUTH 2 N.BERNDT,S.GUNAWAN,N.J.LAWRENCE,E.SCHONBRUNN                 
JRNL        TITL   DIFFERENTIAL BET BROMODOMAIN INHIBITION BY                   
JRNL        TITL 2 DIHYDROPTERIDINONE AND PYRIMIDODIAZEPINONE KINASE            
JRNL        TITL 3 INHIBITORS.                                                  
JRNL        REF    J.MED.CHEM.                                2021              
JRNL        REFN                   ISSN 0022-2623                               
JRNL        PMID   34710325                                                     
JRNL        DOI    10.1021/ACS.JMEDCHEM.1C01096                                 
REMARK   2                                                                      
REMARK   2 RESOLUTION.    1.78 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : PHENIX 1.9_1692                                      
REMARK   3   AUTHORS     : PAUL ADAMS,PAVEL AFONINE,VINCENT CHEN,IAN            
REMARK   3               : DAVIS,KRESHNA GOPAL,RALF GROSSE-KUNSTLEVE,           
REMARK   3               : LI-WEI HUNG,ROBERT IMMORMINO,TOM IOERGER,            
REMARK   3               : AIRLIE MCCOY,ERIK MCKEE,NIGEL MORIARTY,              
REMARK   3               : REETAL PAI,RANDY READ,JANE RICHARDSON,               
REMARK   3               : DAVID RICHARDSON,TOD ROMO,JIM SACCHETTINI,           
REMARK   3               : NICHOLAS SAUTER,JACOB SMITH,LAURENT                  
REMARK   3               : STORONI,TOM TERWILLIGER,PETER ZWART                  
REMARK   3                                                                      
REMARK   3    REFINEMENT TARGET : NULL                                          
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 1.78                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 38.47                          
REMARK   3   MIN(FOBS/SIGMA_FOBS)              : 1.380                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 100.0                          
REMARK   3   NUMBER OF REFLECTIONS             : 15098                          
REMARK   3                                                                      
REMARK   3  FIT TO DATA USED IN REFINEMENT.                                     
REMARK   3   R VALUE     (WORKING + TEST SET) : 0.153                           
REMARK   3   R VALUE            (WORKING SET) : 0.150                           
REMARK   3   FREE R VALUE                     : 0.208                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 5.000                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 755                             
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 38.4762 -  3.0433    1.00     3005   159  0.1594 0.1956        
REMARK   3     2  3.0433 -  2.4157    1.00     2879   151  0.1560 0.2118        
REMARK   3     3  2.4157 -  2.1103    1.00     2815   148  0.1387 0.1906        
REMARK   3     4  2.1103 -  1.9174    1.00     2829   149  0.1385 0.2404        
REMARK   3     5  1.9174 -  1.7800    1.00     2815   148  0.1316 0.2440        
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELLING.                                             
REMARK   3   METHOD USED        : NULL                                          
REMARK   3   SOLVENT RADIUS     : 1.11                                          
REMARK   3   SHRINKAGE RADIUS   : 0.90                                          
REMARK   3   K_SOL              : NULL                                          
REMARK   3   B_SOL              : NULL                                          
REMARK   3                                                                      
REMARK   3  ERROR ESTIMATES.                                                    
REMARK   3   COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED)     : 0.190            
REMARK   3   PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 20.680           
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 15.96                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 21.39                          
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      :  0.010           1164                                  
REMARK   3   ANGLE     :  1.286           1586                                  
REMARK   3   CHIRALITY :  0.045            165                                  
REMARK   3   PLANARITY :  0.006            199                                  
REMARK   3   DIHEDRAL  : 17.165            453                                  
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 5V67 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 29-MAR-17.                  
REMARK 100 THE DEPOSITION ID IS D_1000226952.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 20-APR-14                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : 7.5                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : APS                                
REMARK 200  BEAMLINE                       : 22-ID                              
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : NULL                               
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.00                               
REMARK 200  MONOCHROMATOR                  : ROSENBAUM-ROCK DOUBLE-CRYSTAL      
REMARK 200                                   SI(220)                            
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : CCD                                
REMARK 200  DETECTOR MANUFACTURER          : MARMOSAIC 300 MM CCD               
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : XDS                                
REMARK 200  DATA SCALING SOFTWARE          : XSCALE                             
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 15100                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 1.780                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 38.467                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : -3.000                             
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 100.0                              
REMARK 200  DATA REDUNDANCY                : 7.165                              
REMARK 200  R MERGE                    (I) : 0.06500                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 21.1800                            
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.78                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 1.83                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 100.0                              
REMARK 200  DATA REDUNDANCY IN SHELL       : 7.24                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.33300                            
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 5.920                              
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: 4O70                                                 
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 50.74                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.50                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 12.5 MG/ML BRD4, 5MM HEPES PH 7.5,       
REMARK 280  50MM SODIUM CHLORIDE, 0.5MM DTT, 50MM TRIS PH8.5, 0.1M AMMONIUM,    
REMARK 280  SULFATE, 12.5% PEG 3,350, 10% DMSO, 1 MM VOLASERTIB, VAPOR          
REMARK 280  DIFFUSION, HANGING DROP, TEMPERATURE 291K                           
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       19.12000            
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000       46.72000            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       21.10500            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000       46.72000            
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000       19.12000            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       21.10500            
REMARK 290   SMTRY3   4  0.000000  0.000000 -1.000000        0.00000            
REMARK 290                                                                      
REMARK 290 REMARK: NULL                                                         
REMARK 300                                                                      
REMARK 300 BIOMOLECULE: 1                                                       
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM                
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN                  
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON               
REMARK 300 BURIED SURFACE AREA.                                                 
REMARK 350                                                                      
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN           
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE                
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS          
REMARK 350 GIVEN BELOW.  BOTH NON-CRYSTALLOGRAPHIC AND                          
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.                               
REMARK 350                                                                      
REMARK 350 BIOMOLECULE: 1                                                       
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC                         
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A                                     
REMARK 350   BIOMT1   1  1.000000  0.000000  0.000000        0.00000            
REMARK 350   BIOMT2   1  0.000000  1.000000  0.000000        0.00000            
REMARK 350   BIOMT3   1  0.000000  0.000000  1.000000        0.00000            
REMARK 800                                                                      
REMARK 800 SITE                                                                 
REMARK 800 SITE_IDENTIFIER: AC1                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue IBI A 201                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 202                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue DMS A 203                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC4                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue DMS A 204                 
DBREF  5V67 A   44   168  UNP    O60885   BRD4_HUMAN      44    168             
SEQADV 5V67 SER A   42  UNP  O60885              EXPRESSION TAG                 
SEQADV 5V67 MET A   43  UNP  O60885              EXPRESSION TAG                 
SEQRES   1 A  127  SER MET ASN PRO PRO PRO PRO GLU THR SER ASN PRO ASN          
SEQRES   2 A  127  LYS PRO LYS ARG GLN THR ASN GLN LEU GLN TYR LEU LEU          
SEQRES   3 A  127  ARG VAL VAL LEU LYS THR LEU TRP LYS HIS GLN PHE ALA          
SEQRES   4 A  127  TRP PRO PHE GLN GLN PRO VAL ASP ALA VAL LYS LEU ASN          
SEQRES   5 A  127  LEU PRO ASP TYR TYR LYS ILE ILE LYS THR PRO MET ASP          
SEQRES   6 A  127  MET GLY THR ILE LYS LYS ARG LEU GLU ASN ASN TYR TYR          
SEQRES   7 A  127  TRP ASN ALA GLN GLU CYS ILE GLN ASP PHE ASN THR MET          
SEQRES   8 A  127  PHE THR ASN CYS TYR ILE TYR ASN LYS PRO GLY ASP ASP          
SEQRES   9 A  127  ILE VAL LEU MET ALA GLU ALA LEU GLU LYS LEU PHE LEU          
SEQRES  10 A  127  GLN LYS ILE ASN GLU LEU PRO THR GLU GLU                      
HET    IBI  A 201      45                                                       
HET    EDO  A 202      10                                                       
HET    DMS  A 203      10                                                       
HET    DMS  A 204      10                                                       
HETNAM     IBI N-{TRANS-4-[4-(CYCLOPROPYLMETHYL)PIPERAZIN-1-                    
HETNAM   2 IBI  YL]CYCLOHEXYL}-4-{[(7R)-7-ETHYL-5-METHYL-8-(1-                  
HETNAM   3 IBI  METHYLETHYL)-6-OXO-5,6,7,8-TETRAHYDROPTERIDIN-2-                
HETNAM   4 IBI  YL]AMINO}-3-METHOXYBENZAMIDE                                    
HETNAM     EDO 1,2-ETHANEDIOL                                                   
HETNAM     DMS DIMETHYL SULFOXIDE                                               
HETSYN     IBI VOLASERTIB                                                       
HETSYN     EDO ETHYLENE GLYCOL                                                  
FORMUL   2  IBI    C34 H50 N8 O3                                                
FORMUL   3  EDO    C2 H6 O2                                                     
FORMUL   4  DMS    2(C2 H6 O S)                                                 
FORMUL   6  HOH   *117(H2 O)                                                    
HELIX    1 AA1 THR A   60  VAL A   69  1                                  10    
HELIX    2 AA2 VAL A   69  LYS A   76  1                                   8    
HELIX    3 AA3 ALA A   80  GLN A   84  5                                   5    
HELIX    4 AA4 ASP A   96  ILE A  101  1                                   6    
HELIX    5 AA5 ASP A  106  ASN A  116  1                                  11    
HELIX    6 AA6 ASN A  121  ASN A  140  1                                  20    
HELIX    7 AA7 ASP A  144  ASN A  162  1                                  19    
SITE     1 AC1 14 THR A  60  ASN A  61  GLN A  64  TRP A  81                    
SITE     2 AC1 14 PRO A  82  GLN A  85  VAL A  87  LEU A  92                    
SITE     3 AC1 14 TYR A 139  ASN A 140  PRO A 142  DMS A 204                    
SITE     4 AC1 14 HOH A 313  HOH A 363                                          
SITE     1 AC2  7 ILE A 100  ILE A 101  LYS A 102  THR A 103                    
SITE     2 AC2  7 ASN A 135  ASP A 145  HOH A 306                               
SITE     1 AC3  5 PRO A  56  LYS A  57  LYS A  99  LYS A 102                    
SITE     2 AC3  5 HOH A 359                                                     
SITE     1 AC4  4 TRP A  81  ILE A 138  IBI A 201  HOH A 363                    
CRYST1   38.240   42.210   93.440  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      0.026151  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.023691  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.010702        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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