HEADER TRANSCRIPTION/INHIBITOR 20-JAN-18 5Z5T
TITLE THE FIRST BROMODOMAIN OF BRD4 WITH COMPOUND BDF-2141
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BROMODOMAIN-CONTAINING PROTEIN 4;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: FIRST BROMODOMAIN;
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 BRD4, INHIBITOR, COMPLEX, PROTEIN BINDING, TRANSCRIPTION-INHIBITOR
KEYWDS 2 COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR H.ZHANG,C.LUO
REVDAT 3 22-NOV-23 5Z5T 1 REMARK
REVDAT 2 06-MAR-19 5Z5T 1 JRNL
REVDAT 1 23-JAN-19 5Z5T 0
JRNL AUTH W.CHEN,H.ZHANG,Z.CHEN,H.JIANG,L.LIAO,S.FAN,J.XING,Y.XIE,
JRNL AUTH 2 S.CHEN,H.DING,K.CHEN,H.JIANG,C.LUO,M.ZHENG,Z.YAO,Y.HUANG,
JRNL AUTH 3 Y.ZHANG
JRNL TITL DEVELOPMENT AND EVALUATION OF A NOVEL SERIES OF
JRNL TITL 2 NITROXOLINE-DERIVED BET INHIBITORS WITH ANTITUMOR ACTIVITY
JRNL TITL 3 IN RENAL CELL CARCINOMA.
JRNL REF ONCOGENESIS V. 7 83 2018
JRNL REFN ISSN 2157-9024
JRNL PMID 30385738
JRNL DOI 10.1038/S41389-018-0093-Z
REMARK 2
REMARK 2 RESOLUTION. 1.99 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX (1.10.1_2155)
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) : 1.99
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 40.48
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 1.340
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.6
REMARK 3 NUMBER OF REFLECTIONS : 8839
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.207
REMARK 3 R VALUE (WORKING SET) : 0.204
REMARK 3 FREE R VALUE : 0.244
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 6.170
REMARK 3 FREE R VALUE TEST SET COUNT : 545
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 40.4931 - 3.1604 1.00 2174 144 0.1756 0.2114
REMARK 3 2 3.1604 - 2.5086 1.00 2057 134 0.2196 0.2405
REMARK 3 3 2.5086 - 2.1916 0.99 2041 135 0.2376 0.2874
REMARK 3 4 2.1916 - 1.9912 1.00 2022 132 0.2563 0.3168
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) : 0.170
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 32.310
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) : 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 1086
REMARK 3 ANGLE : 0.955 1479
REMARK 3 CHIRALITY : 0.045 155
REMARK 3 PLANARITY : 0.005 189
REMARK 3 DIHEDRAL : 11.228 658
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 5Z5T COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBJ ON 25-JAN-18.
REMARK 100 THE DEPOSITION ID IS D_1300006524.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 17-OCT-16
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 : BL19U1
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.9785
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : PIXEL
REMARK 200 DETECTOR MANUFACTURER : DECTRIS PILATUS3 S 6M
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : AIMLESS
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 8867
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.991
REMARK 200 RESOLUTION RANGE LOW (A) : 40.480
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 100.0
REMARK 200 DATA REDUNDANCY : 2.000
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 25.2400
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.99
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.06
REMARK 200 COMPLETENESS FOR SHELL (%) : NULL
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : NULL
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: PHASER
REMARK 200 STARTING MODEL: 5H21
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 40.18
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.06
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 10-15% GLYCEROL, 4M SODIUM FORMATE,
REMARK 280 VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 289K
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 16.54950
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 39.06100
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 23.66850
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 39.06100
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 16.54950
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 23.66850
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 465
REMARK 465 MISSING RESIDUES
REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)
REMARK 465
REMARK 465 M RES C SSSEQI
REMARK 465 GLU A 167
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT
REMARK 500
REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI DISTANCE
REMARK 500 OE2 GLU A 163 O HOH A 301 1.84
REMARK 500 NE2 GLN A 62 O HOH A 302 1.94
REMARK 500 OH TYR A 65 O HOH A 303 1.98
REMARK 500 O HOH A 365 O HOH A 373 2.01
REMARK 500 O HOH A 331 O HOH A 353 2.06
REMARK 500 O ILE A 138 O HOH A 304 2.07
REMARK 500 OE1 GLU A 151 O HOH A 305 2.11
REMARK 500 O HOH A 375 O HOH A 378 2.14
REMARK 500 O HOH A 306 O HOH A 345 2.19
REMARK 500
REMARK 500 REMARK: NULL
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 ASN A 140 O HOH A 301 4445 2.10
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 52 108.29 -162.06
REMARK 500 LEU A 94 63.23 -115.96
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 96R A 201
DBREF 5Z5T A 44 167 UNP O60885 BRD4_HUMAN 44 167
SEQADV 5Z5T MET A 43 UNP O60885 INITIATING METHIONINE
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 96R A 201 17
HETNAM 96R 2-AMINO-4-(1H-IMIDAZOL-1-YL)QUINOLIN-8-OL
FORMUL 2 96R C12 H10 N4 O
FORMUL 3 HOH *81(H2 O)
HELIX 1 AA1 THR A 60 VAL A 69 1 10
HELIX 2 AA2 VAL A 69 TRP A 75 1 7
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 ILE A 161 1 18
SITE 1 AC1 11 TRP A 81 PHE A 83 VAL A 87 LEU A 92
SITE 2 AC1 11 TYR A 97 CYS A 136 TYR A 139 ASN A 140
SITE 3 AC1 11 ILE A 146 HOH A 309 HOH A 369
CRYST1 33.099 47.337 78.122 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 0.030212 0.000000 0.000000 0.00000
SCALE2 0.000000 0.021125 0.000000 0.00000
SCALE3 0.000000 0.000000 0.012800 0.00000
(ATOM LINES ARE NOT SHOWN.)
END