HEADER TRANSCRIPTION/TRANSCRIPTION INHIBITOR 28-JUL-17 5WMA
TITLE N-TERMINAL BROMODOMAIN OF BRD4 IN COMPLEX WITH PLX5981
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
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, PLX5981, TRANSCRIPTION-
KEYWDS 2 TRANSCRIPTION INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR Y.ZHANG
REVDAT 3 04-OCT-23 5WMA 1 REMARK
REVDAT 2 13-FEB-19 5WMA 1 JRNL
REVDAT 1 01-AUG-18 5WMA 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. 1.40 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) : 1.40
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 38.67
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 1.340
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.7
REMARK 3 NUMBER OF REFLECTIONS : 26187
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.148
REMARK 3 R VALUE (WORKING SET) : 0.146
REMARK 3 FREE R VALUE : 0.176
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 7.630
REMARK 3 FREE R VALUE TEST SET COUNT : 1324
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 38.6847 - 3.3756 0.98 1842 153 0.1839 0.1761
REMARK 3 2 3.3756 - 2.6795 1.00 1781 147 0.1513 0.1623
REMARK 3 3 2.6795 - 2.3409 1.00 1738 143 0.1429 0.2014
REMARK 3 4 2.3409 - 2.1269 1.00 1756 145 0.1273 0.1636
REMARK 3 5 2.1269 - 1.9744 1.00 1727 143 0.1308 0.1518
REMARK 3 6 1.9744 - 1.8580 1.00 1724 143 0.1299 0.1756
REMARK 3 7 1.8580 - 1.7650 1.00 1717 140 0.1376 0.1747
REMARK 3 8 1.7650 - 1.6881 1.00 1726 143 0.1237 0.1711
REMARK 3 9 1.6881 - 1.6232 1.00 1695 141 0.1148 0.1663
REMARK 3 10 1.6232 - 1.5671 1.00 1713 142 0.1119 0.1738
REMARK 3 11 1.5671 - 1.5181 1.00 1705 141 0.1276 0.1857
REMARK 3 12 1.5181 - 1.4747 1.00 1699 140 0.1348 0.2091
REMARK 3 13 1.4747 - 1.4359 1.00 1700 141 0.1493 0.2138
REMARK 3 14 1.4359 - 1.4009 0.98 1665 137 0.1451 0.2153
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : NULL
REMARK 3 SOLVENT RADIUS : 0.90
REMARK 3 SHRINKAGE RADIUS : 0.60
REMARK 3 K_SOL : 0.41
REMARK 3 B_SOL : 48.38
REMARK 3
REMARK 3 ERROR ESTIMATES.
REMARK 3 COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) : 0.140
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 14.930
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) : 3.47780
REMARK 3 B22 (A**2) : -2.48970
REMARK 3 B33 (A**2) : -0.98810
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 : 0.004 1131
REMARK 3 ANGLE : 0.988 1544
REMARK 3 CHIRALITY : 0.057 163
REMARK 3 PLANARITY : 0.005 199
REMARK 3 DIHEDRAL : 13.953 441
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 5WMA 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_1000229278.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 18-JAN-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 : CLSI
REMARK 200 BEAMLINE : 08ID-1
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.97949
REMARK 200 MONOCHROMATOR : DOUBLE CRYSTAL SI(111)
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : MARMOSAIC 225 MM CCD
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : HKL-2000
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 26278
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.400
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 (%) : 99.9
REMARK 200 DATA REDUNDANCY : 5.600
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 9.8000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.40
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.45
REMARK 200 COMPLETENESS FOR SHELL (%) : NULL
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : 0.11100
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 2OSS
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 42.70
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.15
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1 M BIS-TRIS PROPANE, PH 7.5-8.0,
REMARK 280 11% PEG3350, 0.2 M SODIUM CHLORIDE, 20% ETHYLENE GLYCOL, VAPOR
REMARK 280 DIFFUSION, SITTING DROP, 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 18.61300
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 39.15550
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 22.23500
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 39.15550
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 18.61300
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 22.23500
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: 200 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 7600 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: 3.0 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: CLOSE CONTACTS
REMARK 500
REMARK 500 THE FOLLOWING ATOMS THAT ARE RELATED BY CRYSTALLOGRAPHIC
REMARK 500 SYMMETRY ARE IN CLOSE CONTACT. AN ATOM LOCATED WITHIN 0.15
REMARK 500 ANGSTROMS OF A SYMMETRY RELATED ATOM IS ASSUMED TO BE ON A
REMARK 500 SPECIAL POSITION AND IS, THEREFORE, LISTED IN REMARK 375
REMARK 500 INSTEAD OF REMARK 500. ATOMS WITH NON-BLANK ALTERNATE
REMARK 500 LOCATION INDICATORS ARE NOT INCLUDED IN THE CALCULATIONS.
REMARK 500
REMARK 500 DISTANCE CUTOFF:
REMARK 500 2.2 ANGSTROMS FOR CONTACTS NOT INVOLVING HYDROGEN ATOMS
REMARK 500 1.6 ANGSTROMS FOR CONTACTS INVOLVING HYDROGEN ATOMS
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI SSYMOP DISTANCE
REMARK 500 O HOH A 439 O HOH A 442 3444 2.14
REMARK 500 O HOH A 385 O HOH A 390 4545 2.18
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: TORSION ANGLES
REMARK 500
REMARK 500 TORSION ANGLES OUTSIDE THE EXPECTED RAMACHANDRAN REGIONS:
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT:(10X,I3,1X,A3,1X,A1,I4,A1,4X,F7.2,3X,F7.2)
REMARK 500
REMARK 500 EXPECTED VALUES: GJ KLEYWEGT AND TA JONES (1996). PHI/PSI-
REMARK 500 CHOLOGY: RAMACHANDRAN REVISITED. STRUCTURE 4, 1395 - 1400
REMARK 500
REMARK 500 M RES CSSEQI PSI PHI
REMARK 500 ASN A 52 94.69 -164.54
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 EDO A 201
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 6JC A 202
DBREF 5WMA A 44 168 UNP O60885 BRD4_HUMAN 44 168
SEQADV 5WMA SER A 42 UNP O60885 EXPRESSION TAG
SEQADV 5WMA 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 EDO A 201 10
HET 6JC A 202 27
HETNAM EDO 1,2-ETHANEDIOL
HETNAM 6JC 5-(3,5-DIMETHYL-1,2-OXAZOL-4-YL)-1H-PYRROLO[2,3-
HETNAM 2 6JC B]PYRIDINE
HETSYN EDO ETHYLENE GLYCOL
FORMUL 2 EDO C2 H6 O2
FORMUL 3 6JC C12 H11 N3 O
FORMUL 4 HOH *179(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 6 ILE A 100 ILE A 101 LYS A 102 THR A 103
SITE 2 AC1 6 ASN A 135 HOH A 325
SITE 1 AC2 9 TRP A 81 PRO A 82 PHE A 83 LEU A 94
SITE 2 AC2 9 LYS A 99 ASN A 140 HOH A 307 HOH A 371
SITE 3 AC2 9 HOH A 376
CRYST1 37.226 44.470 78.311 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 0.026863 0.000000 0.000000 0.00000
SCALE2 0.000000 0.022487 0.000000 0.00000
SCALE3 0.000000 0.000000 0.012770 0.00000
(ATOM LINES ARE NOT SHOWN.)
END