HEADER TRANSCRIPTION/TRANSCRIPTION INHIBITOR 28-JUL-17 5WMD
TITLE N-TERMINAL BROMODOMAIN OF BRD4 IN COMPLEX WITH OTX-015
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BROMODOMAIN-CONTAINING PROTEIN 4;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: N-TERMINAL BROMODOMAIN (UNP RESIDUES 44-168);
COMPND 5 SYNONYM: PROTEIN HUNK1;
COMPND 6 ENGINEERED: YES;
COMPND 7 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 GENE: BRD4, HUNK1;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS BROMODOMAIN, BRD4, TRANSCRIPTION, OTX-015, TRANSCRIPTION-
KEYWDS 2 TRANSCRIPTION INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR Y.ZHANG
REVDAT 3 04-OCT-23 5WMD 1 REMARK
REVDAT 2 13-FEB-19 5WMD 1 JRNL
REVDAT 1 01-AUG-18 5WMD 0
JRNL AUTH H.G.OZER,D.EL-GAMAL,B.POWELL,Z.A.HING,J.S.BLACHLY,
JRNL AUTH 2 B.HARRINGTON,S.MITCHELL,N.R.GRIESELHUBER,K.WILLIAMS,T.H.LAI,
JRNL AUTH 3 L.ALINARI,R.A.BAIOCCHI,L.BRINTON,E.BASKIN,M.CANNON,L.BEAVER,
JRNL AUTH 4 V.M.GOETTL,D.M.LUCAS,J.A.WOYACH,D.SAMPATH,A.M.LEHMAN,L.YU,
JRNL AUTH 5 J.ZHANG,Y.MA,Y.ZHANG,W.SPEVAK,S.SHI,P.SEVERSON,R.SHELLOOE,
JRNL AUTH 6 H.CARIAS,G.TSANG,K.DONG,T.EWING,A.MARIMUTHU,C.TANTOY,
JRNL AUTH 7 J.WALTERS,L.SANFTNER,H.REZAEI,M.NESPI,B.MATUSOW,G.HABETS,
JRNL AUTH 8 P.IBRAHIM,C.ZHANG,E.A.MATHE,G.BOLLAG,J.C.BYRD,R.LAPALOMBELLA
JRNL TITL BRD4 PROFILING IDENTIFIES CRITICAL CHRONIC LYMPHOCYTIC
JRNL TITL 2 LEUKEMIA ONCOGENIC CIRCUITS AND REVEALS SENSITIVITY TO
JRNL TITL 3 PLX51107, A NOVEL STRUCTURALLY DISTINCT BET INHIBITOR.
JRNL REF CANCER DISCOV V. 8 458 2018
JRNL REFN ESSN 2159-8290
JRNL PMID 29386193
JRNL DOI 10.1158/2159-8290.CD-17-0902
REMARK 2
REMARK 2 RESOLUTION. 1.27 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX 1.7.3_928
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) : 1.27
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 21.22
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 1.340
REMARK 3 COMPLETENESS FOR RANGE (%) : 95.4
REMARK 3 NUMBER OF REFLECTIONS : 33012
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.146
REMARK 3 R VALUE (WORKING SET) : 0.145
REMARK 3 FREE R VALUE : 0.170
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.010
REMARK 3 FREE R VALUE TEST SET COUNT : 1655
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 21.2221 - 2.9053 0.90 2610 147 0.1885 0.2063
REMARK 3 2 2.9053 - 2.3069 0.98 2731 161 0.1539 0.1855
REMARK 3 3 2.3069 - 2.0156 0.98 2722 149 0.1337 0.1317
REMARK 3 4 2.0156 - 1.8314 0.97 2668 138 0.1276 0.1454
REMARK 3 5 1.8314 - 1.7002 0.97 2645 143 0.1193 0.1556
REMARK 3 6 1.7002 - 1.6000 0.96 2625 125 0.1100 0.1402
REMARK 3 7 1.6000 - 1.5199 0.96 2624 132 0.1005 0.1502
REMARK 3 8 1.5199 - 1.4537 0.95 2594 121 0.0925 0.1451
REMARK 3 9 1.4537 - 1.3978 0.95 2573 130 0.0979 0.1410
REMARK 3 10 1.3978 - 1.3496 0.94 2528 138 0.1087 0.1589
REMARK 3 11 1.3496 - 1.3074 0.94 2512 142 0.1280 0.1723
REMARK 3 12 1.3074 - 1.2700 0.93 2525 129 0.1553 0.1799
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : NULL
REMARK 3 SOLVENT RADIUS : 1.00
REMARK 3 SHRINKAGE RADIUS : 0.73
REMARK 3 K_SOL : 0.42
REMARK 3 B_SOL : 41.88
REMARK 3
REMARK 3 ERROR ESTIMATES.
REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : 0.120
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 13.170
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : NULL
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 2.47500
REMARK 3 B22 (A**2) : -3.68170
REMARK 3 B33 (A**2) : 1.20680
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 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 : 0.012 1145
REMARK 3 ANGLE : 1.541 1570
REMARK 3 CHIRALITY : 0.134 164
REMARK 3 PLANARITY : 0.008 201
REMARK 3 DIHEDRAL : 13.480 445
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 5WMD COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 01-AUG-17.
REMARK 100 THE DEPOSITION ID IS D_1000229283.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 20-JUN-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 : SSRL
REMARK 200 BEAMLINE : BL7-1
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.1271
REMARK 200 MONOCHROMATOR : SI(111)
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 315R
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 40196
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.180
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 93.6
REMARK 200 DATA REDUNDANCY : 5.900
REMARK 200 R MERGE (I) : 0.03700
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 25.5000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.18
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.22
REMARK 200 COMPLETENESS FOR SHELL (%) : NULL
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : 0.23900
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : NULL
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: MOLREP
REMARK 200 STARTING MODEL: PDB ENTRY 5WMA
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 42.20
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.13
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1 M BIS-TRIS, PH 7.5, 19% PEG3350,
REMARK 280 0.2 M LITHIUM SULFATE, VAPOR DIFFUSION, SITTING DROP,
REMARK 280 TEMPERATURE 277K
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 18.43250
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 38.92300
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 22.28350
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 38.92300
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 18.43250
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 22.28350
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 TOTAL BURIED SURFACE AREA: 0 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 7690 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: 0.0 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 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 99.65 -160.31
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 455 DISTANCE = 7.24 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 6JE A 201
DBREF 5WMD A 44 168 UNP O60885 BRD4_HUMAN 44 168
SEQADV 5WMD GLY A 42 UNP O60885 EXPRESSION TAG
SEQADV 5WMD MET A 43 UNP O60885 EXPRESSION TAG
SEQADV 5WMD ALA A 96 UNP O60885 ASP 96 ENGINEERED MUTATION
SEQRES 1 A 127 GLY 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 ALA 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 6JE A 201 56
HETNAM 6JE 2-[(6S)-4-(4-CHLOROPHENYL)-2,3,9-TRIMETHYL-6H-THIENO[3,
HETNAM 2 6JE 2-F][1,2,4]TRIAZOLO[4,3-A][1,4]DIAZEPIN-6-YL]-N-(4-
HETNAM 3 6JE HYDROXYPHENYL)ACETAMIDE
FORMUL 2 6JE C25 H22 CL N5 O2 S
FORMUL 3 HOH *155(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 ALA 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 13 PRO A 53 TRP A 81 PRO A 82 LEU A 92
SITE 2 AC1 13 LEU A 94 LYS A 99 LYS A 102 ASN A 140
SITE 3 AC1 13 ILE A 146 MET A 149 HOH A 306 HOH A 330
SITE 4 AC1 13 HOH A 374
CRYST1 36.865 44.567 77.846 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 0.027126 0.000000 0.000000 0.00000
SCALE2 0.000000 0.022438 0.000000 0.00000
SCALE3 0.000000 0.000000 0.012846 0.00000
(ATOM LINES ARE NOT SHOWN.)
END