HEADER TRANSCRIPTION/INHIBITOR 01-OCT-16 5TI5
TITLE CRYSTAL STRUCTURE OF THE FIRST BROMODOMAIN OF HUMAN BRD4 IN COMPLEX
TITLE 2 WITH INHIBITOR 8841880
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;
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: 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, CELL CYCLE, INHIBITOR,
KEYWDS 3 TRANSCRIPTION-INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR J.-Y.ZHU,S.W.J.EMBER,E.SCHONBRUNN
REVDAT 5 06-MAR-24 5TI5 1 REMARK
REVDAT 4 04-DEC-19 5TI5 1 REMARK
REVDAT 3 20-SEP-17 5TI5 1 JRNL
REVDAT 2 13-SEP-17 5TI5 1 REMARK
REVDAT 1 09-AUG-17 5TI5 0
JRNL AUTH B.K.ALLEN,S.MEHTA,S.W.J.EMBER,J.Y.ZHU,E.SCHONBRUNN,N.G.AYAD,
JRNL AUTH 2 S.C.SCHURER
JRNL TITL IDENTIFICATION OF A NOVEL CLASS OF BRD4 INHIBITORS BY
JRNL TITL 2 COMPUTATIONAL SCREENING AND BINDING SIMULATIONS.
JRNL REF ACS OMEGA V. 2 4760 2017
JRNL REFN ESSN 2470-1343
JRNL PMID 28884163
JRNL DOI 10.1021/ACSOMEGA.7B00553
REMARK 2
REMARK 2 RESOLUTION. 1.83 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX 1.8.4_1496
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) : 1.83
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 19.46
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 1.360
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.8
REMARK 3 NUMBER OF REFLECTIONS : 11741
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.167
REMARK 3 R VALUE (WORKING SET) : 0.164
REMARK 3 FREE R VALUE : 0.214
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT : 587
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 19.4586 - 2.9026 1.00 2906 153 0.1613 0.1815
REMARK 3 2 2.9026 - 2.3051 1.00 2774 146 0.1715 0.2429
REMARK 3 3 2.3051 - 2.0140 1.00 2735 143 0.1534 0.2176
REMARK 3 4 2.0140 - 1.8300 1.00 2739 145 0.1752 0.3055
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) : 0.230
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 25.510
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 19.42
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 27.00
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 : 0.007 1129
REMARK 3 ANGLE : 1.097 1530
REMARK 3 CHIRALITY : 0.037 158
REMARK 3 PLANARITY : 0.004 196
REMARK 3 DIHEDRAL : 18.152 450
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 5TI5 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 05-OCT-16.
REMARK 100 THE DEPOSITION ID IS D_1000224282.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 02-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) : N
REMARK 200 RADIATION SOURCE : ROTATING ANODE
REMARK 200 BEAMLINE : NULL
REMARK 200 X-RAY GENERATOR MODEL : RIGAKU MICROMAX-007 HF
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.54
REMARK 200 MONOCHROMATOR : MIRROR
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : IMAGE PLATE
REMARK 200 DETECTOR MANUFACTURER : RIGAKU RAXIS HTC
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : XSCALE
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 11742
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.830
REMARK 200 RESOLUTION RANGE LOW (A) : 19.457
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : -3.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.7
REMARK 200 DATA REDUNDANCY : 6.900
REMARK 200 R MERGE (I) : 0.08100
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 14.8500
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.83
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.88
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.9
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : 0.38900
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 4.810
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: NULL
REMARK 200 SOFTWARE USED: PHASER
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 41.56
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.10
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 8841880, 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 17.56000
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 38.91500
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 23.25500
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 38.91500
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 17.56000
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 23.25500
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 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 93.15 -164.57
REMARK 500 LEU A 94 68.88 -119.76
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 7CN 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 EDO A 203
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 204
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 205
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 5TI2 RELATED DB: PDB
REMARK 900 RELATED ID: 5TI3 RELATED DB: PDB
REMARK 900 RELATED ID: 5TI4 RELATED DB: PDB
REMARK 900 RELATED ID: 5TI6 RELATED DB: PDB
REMARK 900 RELATED ID: 5TI7 RELATED DB: PDB
DBREF 5TI5 A 44 168 UNP O60885 BRD4_HUMAN 44 168
SEQADV 5TI5 SER A 42 UNP O60885 EXPRESSION TAG
SEQADV 5TI5 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 7CN A 201 23
HET EDO A 202 4
HET EDO A 203 4
HET EDO A 204 4
HET EDO A 205 4
HETNAM 7CN 3-BROMO-N-[3-(2-OXO-2,3-DIHYDRO-1H-PYRROL-1-YL)
HETNAM 2 7CN PHENYL]BENZENE-1-SULFONAMIDE
HETNAM EDO 1,2-ETHANEDIOL
HETSYN EDO ETHYLENE GLYCOL
FORMUL 2 7CN C16 H13 BR N2 O3 S
FORMUL 3 EDO 4(C2 H6 O2)
FORMUL 7 HOH *65(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 GLU A 163 1 20
SITE 1 AC1 10 PRO A 82 LEU A 92 LYS A 99 ILE A 100
SITE 2 AC1 10 ASN A 140 MET A 149 EDO A 204 HOH A 304
SITE 3 AC1 10 HOH A 306 HOH A 324
SITE 1 AC2 5 ILE A 100 ILE A 101 LYS A 102 THR A 103
SITE 2 AC2 5 ASN A 135
SITE 1 AC3 6 ARG A 58 THR A 60 GLN A 62 ASN A 121
SITE 2 AC3 6 ALA A 122 GLU A 167
SITE 1 AC4 5 ASP A 144 ASP A 145 ILE A 146 7CN A 201
SITE 2 AC4 5 HOH A 341
SITE 1 AC5 4 ILE A 138 GLN A 159 ASN A 162 GLU A 163
CRYST1 35.120 46.510 77.830 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 0.028474 0.000000 0.000000 0.00000
SCALE2 0.000000 0.021501 0.000000 0.00000
SCALE3 0.000000 0.000000 0.012849 0.00000
(ATOM LINES ARE NOT SHOWN.)
END