HEADER TRANSCRIPTION 28-AUG-18 6AJX
TITLE CRYSTAL STRUCTURE OF BRD4 IN COMPLEX WITH ISOLIQUIRITIGENIN IN THE
TITLE 2 ABSENCE OF DMSO
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BROMODOMAIN-CONTAINING PROTEIN 4;
COMPND 3 CHAIN: A;
COMPND 4 SYNONYM: PROTEIN HUNK1;
COMPND 5 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, INHIBITOR, ISOLIQUIRITIGENIN, TRANSCRIPTION
EXPDTA X-RAY DIFFRACTION
AUTHOR T.YOKOYAMA,K.MATSUMOTO,Y.NABESHIMA,M.MIZUGUCHI
REVDAT 1 12-JUN-19 6AJX 0
JRNL AUTH T.YOKOYAMA,K.MATSUMOTO,A.OSTERMANN,T.E.SCHRADER,Y.NABESHIMA,
JRNL AUTH 2 M.MIZUGUCHI
JRNL TITL STRUCTURAL AND THERMODYNAMIC CHARACTERIZATION OF THE BINDING
JRNL TITL 2 OF ISOLIQUIRITIGENIN TO THE FIRST BROMODOMAIN OF BRD4.
JRNL REF FEBS J. V. 286 1656 2019
JRNL REFN ISSN 1742-464X
JRNL PMID 30565859
JRNL DOI 10.1111/FEBS.14736
REMARK 2
REMARK 2 RESOLUTION. 1.89 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX (1.12-2829_1069: ???)
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) : 1.89
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 30.29
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 1.360
REMARK 3 COMPLETENESS FOR RANGE (%) : 98.3
REMARK 3 NUMBER OF REFLECTIONS : 10075
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.206
REMARK 3 R VALUE (WORKING SET) : 0.204
REMARK 3 FREE R VALUE : 0.237
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT : 504
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 30.2924 - 2.9955 0.96 2434 129 0.1800 0.1952
REMARK 3 2 2.9955 - 2.3779 0.99 2396 126 0.2366 0.2749
REMARK 3 3 2.3779 - 2.0774 1.00 2393 125 0.2237 0.2971
REMARK 3 4 2.0774 - 1.8875 0.99 2348 124 0.2408 0.3122
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) : 0.180
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 36.090
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 : 0.006 1156
REMARK 3 ANGLE : 0.810 1577
REMARK 3 CHIRALITY : 0.069 165
REMARK 3 PLANARITY : 0.006 203
REMARK 3 DIHEDRAL : 21.481 446
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : 1
REMARK 3 TLS GROUP : 1
REMARK 3 SELECTION: (CHAIN A AND RESID 37:166)
REMARK 3 ORIGIN FOR THE GROUP (A): -10.5502 -1.8287 8.5479
REMARK 3 T TENSOR
REMARK 3 T11: 0.2753 T22: 0.2583
REMARK 3 T33: 0.2449 T12: -0.0445
REMARK 3 T13: 0.0295 T23: -0.0124
REMARK 3 L TENSOR
REMARK 3 L11: 1.8150 L22: 4.7993
REMARK 3 L33: 2.3642 L12: -0.5971
REMARK 3 L13: -0.1460 L23: -0.1588
REMARK 3 S TENSOR
REMARK 3 S11: 0.0230 S12: 0.0048 S13: 0.0422
REMARK 3 S21: -0.1808 S22: 0.0492 S23: -0.2010
REMARK 3 S31: -0.2267 S32: 0.0943 S33: -0.0640
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 6AJX COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBJ ON 12-SEP-18.
REMARK 100 THE DEPOSITION ID IS D_1300008893.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 15-NOV-17
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 : PHOTON FACTORY
REMARK 200 BEAMLINE : BL-5A
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 315R
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : XSCALE
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 10088
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.887
REMARK 200 RESOLUTION RANGE LOW (A) : 40.300
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 98.4
REMARK 200 DATA REDUNDANCY : 5.800
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 17.1000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.89
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.95
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: NULL
REMARK 200 SOFTWARE USED: MOLREP
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 34.19
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 1.87
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 4M SODIUM FORMATE, 0.1M TRIS-HCL PH 8,
REMARK 280 VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 293K
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 16.41500
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 39.25550
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 23.43750
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 39.25550
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 16.41500
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 23.43750
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: 650 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 8080 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -15.0 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 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 MET A 34
REMARK 465 HIS A 35
REMARK 465 HIS A 36
REMARK 465 GLU A 167
REMARK 465 GLU A 168
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 HIS A 40 84.23 -69.16
REMARK 500 ASN A 52 105.59 -160.70
REMARK 500
REMARK 500 REMARK: NULL
REMARK 620
REMARK 620 METAL COORDINATION
REMARK 620 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 620 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE):
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 NA A 203 NA
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 TYR A 65 OH
REMARK 620 2 LYS A 160 O 89.5
REMARK 620 3 GLU A 163 O 90.7 93.1
REMARK 620 N 1 2
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 NA A 202 NA
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 TYR A 137 O
REMARK 620 2 ILE A 138 O 86.6
REMARK 620 3 ASN A 140 O 69.9 96.9
REMARK 620 4 GLU A 163 OE1 20.6 101.5 82.3
REMARK 620 5 GLU A 163 OE2 24.2 104.8 83.7 3.8
REMARK 620 N 1 2 3 4
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue HCC A 201
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue NA A 202
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue NA A 203
DBREF 6AJX A 42 168 UNP O60885 BRD4_HUMAN 42 168
SEQADV 6AJX MET A 34 UNP O60885 EXPRESSION TAG
SEQADV 6AJX HIS A 35 UNP O60885 EXPRESSION TAG
SEQADV 6AJX HIS A 36 UNP O60885 EXPRESSION TAG
SEQADV 6AJX HIS A 37 UNP O60885 EXPRESSION TAG
SEQADV 6AJX HIS A 38 UNP O60885 EXPRESSION TAG
SEQADV 6AJX HIS A 39 UNP O60885 EXPRESSION TAG
SEQADV 6AJX HIS A 40 UNP O60885 EXPRESSION TAG
SEQADV 6AJX MET A 41 UNP O60885 EXPRESSION TAG
SEQRES 1 A 135 MET HIS HIS HIS HIS HIS HIS MET SER THR ASN PRO PRO
SEQRES 2 A 135 PRO PRO GLU THR SER ASN PRO ASN LYS PRO LYS ARG GLN
SEQRES 3 A 135 THR ASN GLN LEU GLN TYR LEU LEU ARG VAL VAL LEU LYS
SEQRES 4 A 135 THR LEU TRP LYS HIS GLN PHE ALA TRP PRO PHE GLN GLN
SEQRES 5 A 135 PRO VAL ASP ALA VAL LYS LEU ASN LEU PRO ASP TYR TYR
SEQRES 6 A 135 LYS ILE ILE LYS THR PRO MET ASP MET GLY THR ILE LYS
SEQRES 7 A 135 LYS ARG LEU GLU ASN ASN TYR TYR TRP ASN ALA GLN GLU
SEQRES 8 A 135 CYS ILE GLN ASP PHE ASN THR MET PHE THR ASN CYS TYR
SEQRES 9 A 135 ILE TYR ASN LYS PRO GLY ASP ASP ILE VAL LEU MET ALA
SEQRES 10 A 135 GLU ALA LEU GLU LYS LEU PHE LEU GLN LYS ILE ASN GLU
SEQRES 11 A 135 LEU PRO THR GLU GLU
HET HCC A 201 19
HET NA A 202 1
HET NA A 203 1
HETNAM HCC 2',4,4'-TRIHYDROXYCHALCONE
HETNAM NA SODIUM ION
FORMUL 2 HCC C15 H12 O4
FORMUL 3 NA 2(NA 1+)
FORMUL 5 HOH *43(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 ASN A 162 1 19
LINK OH TYR A 65 NA NA A 203 1555 1555 2.40
LINK O TYR A 137 NA NA A 202 1555 1555 2.32
LINK O ILE A 138 NA NA A 202 1555 1555 2.49
LINK O ASN A 140 NA NA A 202 1555 1555 2.44
LINK O LYS A 160 NA NA A 203 1555 1555 2.43
LINK O GLU A 163 NA NA A 203 1555 1555 2.37
LINK OE1 GLU A 163 NA NA A 202 1555 4545 2.44
LINK OE2 GLU A 163 NA NA A 202 1555 4545 2.40
SITE 1 AC1 12 PRO A 82 VAL A 87 LEU A 92 LEU A 94
SITE 2 AC1 12 ASP A 96 TYR A 97 LYS A 99 ILE A 100
SITE 3 AC1 12 CYS A 136 ASN A 140 HOH A 302 HOH A 308
SITE 1 AC2 4 TYR A 137 ILE A 138 ASN A 140 GLU A 163
SITE 1 AC3 3 TYR A 65 LYS A 160 GLU A 163
CRYST1 32.830 46.875 78.511 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 0.030460 0.000000 0.000000 0.00000
SCALE2 0.000000 0.021333 0.000000 0.00000
SCALE3 0.000000 0.000000 0.012737 0.00000
(ATOM LINES ARE NOT SHOWN.)
END