HEADER SIGNALING PROTEIN/INHIBITOR 03-JAN-17 5UF0
TITLE BRD4_BD2-A-35165
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 HELIX BUNDLE, SIGNALING PROTEIN-INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR C.H.PARK
REVDAT 2 06-MAR-24 5UF0 1 REMARK
REVDAT 1 28-JUN-17 5UF0 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. 1.35 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER-TNT
REMARK 3 AUTHORS : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,
REMARK 3 : PACIOREK,ROVERSI,SMART,VONRHEIN,WOMACK,
REMARK 3 : MATTHEWS,TEN EYCK,TRONRUD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.35
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 36.51
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 COMPLETENESS FOR RANGE (%) : 98.0
REMARK 3 NUMBER OF REFLECTIONS : 30952
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) : 0.180
REMARK 3 R VALUE (WORKING SET) : 0.179
REMARK 3 FREE R VALUE : 0.201
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.060
REMARK 3 FREE R VALUE TEST SET COUNT : 1565
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 : 16
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 1.35
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 1.39
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 82.66
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 2358
REMARK 3 BIN R VALUE (WORKING + TEST SET) : NULL
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 2232
REMARK 3 BIN R VALUE (WORKING SET) : 0.2270
REMARK 3 BIN FREE R VALUE : 0.2510
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.34
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 126
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : NULL
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 886
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 16
REMARK 3 SOLVENT ATOMS : 196
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 25.04
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -5.72650
REMARK 3 B22 (A**2) : 3.71180
REMARK 3 B33 (A**2) : 2.01470
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) : 0.170
REMARK 3 DPI (BLOW EQ-10) BASED ON R VALUE (A) : 0.056
REMARK 3 DPI (BLOW EQ-9) BASED ON FREE R VALUE (A) : 0.057
REMARK 3 DPI (CRUICKSHANK) BASED ON R VALUE (A) : 0.049
REMARK 3 DPI (CRUICKSHANK) BASED ON FREE R VALUE (A) : 0.051
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 : 0.959
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.959
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : 931 ; 2.000 ; HARMONIC
REMARK 3 BOND ANGLES : 1247 ; 2.000 ; HARMONIC
REMARK 3 TORSION ANGLES : 333 ; 2.000 ; SINUSOIDAL
REMARK 3 TRIGONAL CARBON PLANES : 21 ; 2.000 ; HARMONIC
REMARK 3 GENERAL PLANES : 138 ; 5.000 ; HARMONIC
REMARK 3 ISOTROPIC THERMAL FACTORS : 931 ; 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 : 110 ; 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 : 1226 ; 4.000 ; SEMIHARMONIC
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.010
REMARK 3 BOND ANGLES (DEGREES) : 0.96
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 3.40
REMARK 3 OTHER TORSION ANGLES (DEGREES) : 16.12
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 5UF0 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_1000224161.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 09-AUG-10
REMARK 200 TEMPERATURE (KELVIN) : 100.0
REMARK 200 PH : 7.0
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 300K
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS 2.11.7
REMARK 200 DATA SCALING SOFTWARE : SCALA 3.20
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 31000
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.350
REMARK 200 RESOLUTION RANGE LOW (A) : 73.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 98.0
REMARK 200 DATA REDUNDANCY : 6.100
REMARK 200 R MERGE (I) : NULL
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 19.4000
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 (%): 55.29
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.75
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PROTEIN BUFFER : PH 7.5 10 MM HEPES
REMARK 280 100 MM NACL 5MM DTT CRYSTALLIZATION : 15 %(V/V) ETHANOL TRIS PH
REMARK 280 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 28.52450
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 36.51500
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 28.52450
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 36.51500
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: 6890 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 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 SER A 349
REMARK 525
REMARK 525 SOLVENT
REMARK 525
REMARK 525 THE SOLVENT MOLECULES HAVE CHAIN IDENTIFIERS THAT
REMARK 525 INDICATE THE POLYMER CHAIN WITH WHICH THEY ARE MOST
REMARK 525 CLOSELY ASSOCIATED. THE REMARK LISTS ALL THE SOLVENT
REMARK 525 MOLECULES WHICH ARE MORE THAN 5A AWAY FROM THE
REMARK 525 NEAREST POLYMER CHAIN (M = MODEL NUMBER;
REMARK 525 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE
REMARK 525 NUMBER; I=INSERTION CODE):
REMARK 525
REMARK 525 M RES CSSEQI
REMARK 525 HOH A 795 DISTANCE = 6.22 ANGSTROMS
REMARK 525 HOH A 796 DISTANCE = 7.17 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 89J A 501
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 5UEZ RELATED DB: PDB
REMARK 900 RELATED ID: 5UEY RELATED DB: PDB
REMARK 900 RELATED ID: 5UEX 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 5UF0 A 352 457 UNP O60885 BRD4_HUMAN 352 457
SEQADV 5UF0 SER A 349 UNP O60885 EXPRESSION TAG
SEQADV 5UF0 HIS A 350 UNP O60885 EXPRESSION TAG
SEQADV 5UF0 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 89J A 501 16
HETNAM 89J 2-METHYL-5-(METHYLAMINO)-6-PHENYLPYRIDAZIN-3(2H)-ONE
FORMUL 2 89J C12 H13 N3 O
FORMUL 3 HOH *196(H2 O)
HELIX 1 AA1 HIS A 350 PHE A 365 1 16
HELIX 2 AA2 ALA A 366 LYS A 368 5 3
HELIX 3 AA3 HIS A 369 TRP A 374 1 6
HELIX 4 AA4 PRO A 375 TYR A 377 5 3
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 MET A 457 1 21
SITE 1 AC1 6 VAL A 380 CYS A 429 ASN A 433 HOH A 601
SITE 2 AC1 6 HOH A 644 HOH A 714
CRYST1 57.049 73.030 33.596 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 0.017529 0.000000 0.000000 0.00000
SCALE2 0.000000 0.013693 0.000000 0.00000
SCALE3 0.000000 0.000000 0.029765 0.00000
(ATOM LINES ARE NOT SHOWN.)
END