HEADER SIGNALING PROTEIN/INHIBITOR 03-JAN-17 5UEX
TITLE BRD4_BD2_A-1497627
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BROMODOMAIN-CONTAINING PROTEIN 4;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: RESIDUES 352-457;
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-PICHIA PASTORIS SHUTTLE VECTOR
SOURCE 7 PPPARG4;
SOURCE 8 EXPRESSION_SYSTEM_TAXID: 1182032
KEYWDS SIGNALING PROTEIN-INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR C.H.PARK
REVDAT 3 06-MAR-24 5UEX 1 REMARK
REVDAT 2 24-MAY-17 5UEX 1 JRNL
REVDAT 1 10-MAY-17 5UEX 0
JRNL AUTH L.WANG,J.K.PRATT,T.SOLTWEDEL,G.S.SHEPPARD,S.D.FIDANZE,D.LIU,
JRNL AUTH 2 L.A.HASVOLD,R.A.MANTEI,J.H.HOLMS,W.J.MCCLELLAN,M.D.WENDT,
JRNL AUTH 3 C.WADA,R.FREY,T.M.HANSEN,R.HUBBARD,C.H.PARK,L.LI,T.J.MAGOC,
JRNL AUTH 4 D.H.ALBERT,X.LIN,S.E.WARDER,P.KOVAR,X.HUANG,D.WILCOX,R.WANG,
JRNL AUTH 5 G.RAJARAMAN,A.M.PETROS,C.W.HUTCHINS,S.C.PANCHAL,C.SUN,
JRNL AUTH 6 S.W.ELMORE,Y.SHEN,W.M.KATI,K.F.MCDANIEL
JRNL TITL FRAGMENT-BASED, STRUCTURE-ENABLED DISCOVERY OF NOVEL
JRNL TITL 2 PYRIDONES AND PYRIDONE MACROCYCLES AS POTENT BROMODOMAIN AND
JRNL TITL 3 EXTRA-TERMINAL DOMAIN (BET) FAMILY BROMODOMAIN INHIBITORS.
JRNL REF J. MED. CHEM. V. 60 3828 2017
JRNL REFN ISSN 1520-4804
JRNL PMID 28368119
JRNL DOI 10.1021/ACS.JMEDCHEM.7B00017
REMARK 2
REMARK 2 RESOLUTION. 2.29 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER 2.11.7
REMARK 3 AUTHORS : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,
REMARK 3 : PACIOREK,ROVERSI,SHARFF,SMART,VONRHEIN,
REMARK 3 : WOMACK,MATTHEWS,TEN EYCK,TRONRUD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.29
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 42.76
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 98.6
REMARK 3 NUMBER OF REFLECTIONS : 6154
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 CROSS-VALIDATION METHOD : THROUGHOUT
REMARK 3 FREE R VALUE TEST SET SELECTION : RANDOM
REMARK 3 R VALUE (WORKING + TEST SET) : 0.238
REMARK 3 R VALUE (WORKING SET) : 0.236
REMARK 3 FREE R VALUE : 0.279
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 4.650
REMARK 3 FREE R VALUE TEST SET COUNT : 286
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : 0.020
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 5
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 2.29
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 2.56
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 97.99
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 1704
REMARK 3 BIN R VALUE (WORKING + TEST SET) : 0.2940
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 1617
REMARK 3 BIN R VALUE (WORKING SET) : 0.2920
REMARK 3 BIN FREE R VALUE : 0.3310
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.11
REMARK 3 BIN FREE R VALUE TEST SET COUNT : NULL
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : 0.000
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 882
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 34
REMARK 3 SOLVENT ATOMS : 93
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 45.25
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 45.34
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -21.59950
REMARK 3 B22 (A**2) : 19.33010
REMARK 3 B33 (A**2) : 2.26940
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 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.400
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : 0.478
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : 0.275
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : 0.381
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : 0.258
REMARK 3
REMARK 3 REFERENCES: BLOW, D. (2002) ACTA CRYST D58, 792-797
REMARK 3 CRUICKSHANK, D.W.J. (1999) ACTA CRYST D55, 583-601
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.887
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.847
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 966 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 1323 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 322 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 20 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 149 ; 5.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 966 ; 20.000 ; HARMONIC
REMARK 3 BAD NON-BONDED CONTACTS : NULL ; NULL ; NULL
REMARK 3 IMPROPER TORSIONS : NULL ; NULL ; NULL
REMARK 3 PSEUDOROTATION ANGLES : NULL ; NULL ; NULL
REMARK 3 CHIRAL IMPROPER TORSION : 111 ; 5.000 ; SEMIHARMONIC
REMARK 3 SUM OF OCCUPANCIES : NULL ; NULL ; NULL
REMARK 3 UTILITY DISTANCES : NULL ; NULL ; NULL
REMARK 3 UTILITY ANGLES : NULL ; NULL ; NULL
REMARK 3 UTILITY TORSION : NULL ; NULL ; NULL
REMARK 3 IDEAL-DIST CONTACT TERM : 1154 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.008
REMARK 3 BOND ANGLES (DEGREES) : 0.97
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 1.67
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 18.11
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 5UEX COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 12-JAN-17.
REMARK 100 THE DEPOSITION ID IS D_1000224213.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 12-JUN-13
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 : APS
REMARK 200 BEAMLINE : 17-ID
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.0
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : PIXEL
REMARK 200 DETECTOR MANUFACTURER : DECTRIS PILATUS 6M
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS 2.11.7
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 6417
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.270
REMARK 200 RESOLUTION RANGE LOW (A) : 42.800
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.6
REMARK 200 DATA REDUNDANCY : 6.000
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 31.9000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : NULL
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : NULL
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: NULL
REMARK 200 STARTING MODEL: APO-BRD4_BD2
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 51.38
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.53
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PROTEIN BUFFER : 10 MM HEPES PH 7.5
REMARK 280 100MM NACL, 5 MM DTT CRYSTALLIZATION : 15 % (V/V) ETHANOL, TRIS
REMARK 280 PH 7.0, VAPOR DIFFUSION, TEMPERATURE 277K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 2
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,-Y,Z
REMARK 290 3555 -X+1/2,Y+1/2,-Z
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 0.00000
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 26.12200
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 37.21050
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 26.12200
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 37.21050
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: 6670 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 470
REMARK 470 MISSING ATOM
REMARK 470 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;
REMARK 470 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;
REMARK 470 I=INSERTION CODE):
REMARK 470 M RES CSSEQI ATOMS
REMARK 470 LYS A 355 CD CE NZ
REMARK 470 LYS A 378 CD CE NZ
REMARK 470 GLN A 416 CG CD OE1 NE2
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 LYS A 456 48.41 -86.01
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 89D A 501
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 5UF0 RELATED DB: PDB
REMARK 900 RELATED ID: 5UEZ RELATED DB: PDB
REMARK 900 RELATED ID: 5UEY RELATED DB: PDB
REMARK 900 RELATED ID: 5UEV RELATED DB: PDB
REMARK 900 RELATED ID: 5UEP RELATED DB: PDB
REMARK 900 RELATED ID: 5UET RELATED DB: PDB
REMARK 900 RELATED ID: 5UES RELATED DB: PDB
REMARK 900 RELATED ID: 5UER RELATED DB: PDB
REMARK 900 RELATED ID: 5UEQ RELATED DB: PDB
REMARK 900 RELATED ID: 5UEU RELATED DB: PDB
REMARK 900 RELATED ID: 5UEO RELATED DB: PDB
REMARK 900 RELATED ID: 5UEW RELATED DB: PDB
DBREF 5UEX A 352 457 UNP O60885 BRD4_HUMAN 352 457
SEQADV 5UEX SER A 349 UNP O60885 EXPRESSION TAG
SEQADV 5UEX HIS A 350 UNP O60885 EXPRESSION TAG
SEQADV 5UEX MET A 351 UNP O60885 EXPRESSION TAG
SEQRES 1 A 109 SER HIS MET GLU GLN LEU LYS CYS CYS SER GLY ILE LEU
SEQRES 2 A 109 LYS GLU MET PHE ALA LYS LYS HIS ALA ALA TYR ALA TRP
SEQRES 3 A 109 PRO PHE TYR LYS PRO VAL ASP VAL GLU ALA LEU GLY LEU
SEQRES 4 A 109 HIS ASP TYR CYS ASP ILE ILE LYS HIS PRO MET ASP MET
SEQRES 5 A 109 SER THR ILE LYS SER LYS LEU GLU ALA ARG GLU TYR ARG
SEQRES 6 A 109 ASP ALA GLN GLU PHE GLY ALA ASP VAL ARG LEU MET PHE
SEQRES 7 A 109 SER ASN CYS TYR LYS TYR ASN PRO PRO ASP HIS GLU VAL
SEQRES 8 A 109 VAL ALA MET ALA ARG LYS LEU GLN ASP VAL PHE GLU MET
SEQRES 9 A 109 ARG PHE ALA LYS MET
HET 89D A 501 58
HETNAM 89D 17-{[ETHYL(DIHYDROXY)-LAMBDA~4~-SULFANYL]AMINO}-11,13-
HETNAM 2 89D DIFLUORO-2-METHYL-6,7,8,9-TETRAHYDRODIBENZO[4,5:7,
HETNAM 3 89D 8][1,6]DIOXACYCLODODECINO[3,2-C]PYRIDIN-3(2H)-ONE
FORMUL 2 89D C24 H26 F2 N2 O5 S
FORMUL 3 HOH *93(H2 O)
HELIX 1 AA1 SER A 349 ALA A 366 1 18
HELIX 2 AA2 HIS A 369 TRP A 374 1 6
HELIX 3 AA3 PRO A 375 TYR A 377 5 3
HELIX 4 AA4 ASP A 381 GLY A 386 1 6
HELIX 5 AA5 ASP A 389 ILE A 394 1 6
HELIX 6 AA6 ASP A 399 ALA A 409 1 11
HELIX 7 AA7 ASP A 414 ASN A 433 1 20
HELIX 8 AA8 HIS A 437 LYS A 456 1 20
SITE 1 AC1 13 TRP A 374 PRO A 375 PHE A 376 LYS A 378
SITE 2 AC1 13 PRO A 379 VAL A 380 ASP A 381 LEU A 385
SITE 3 AC1 13 ASN A 433 HIS A 437 GLU A 438 VAL A 439
SITE 4 AC1 13 HOH A 601
CRYST1 52.244 74.421 33.333 90.00 90.00 90.00 P 21 21 2 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 0.019141 0.000000 0.000000 0.00000
SCALE2 0.000000 0.013437 0.000000 0.00000
SCALE3 0.000000 0.000000 0.030000 0.00000
(ATOM LINES ARE NOT SHOWN.)
END