HEADER SIGNALING PROTEIN 26-NOV-14 4X2I
TITLE DISCOVERY OF BENZOTRIAZOLO DIAZEPINES AS ORALLY-ACTIVE INHIBITORS OF
TITLE 2 BET BROMODOMAINS: CRYSTAL STRUCTURE OF BRD4 WITH CPI-13
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BROMODOMAIN-CONTAINING PROTEIN 4;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: BROMO 1 DOMAIN (UNP RESIDUES 42-166);
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 BET, CPI-13, SIGNALING PROTEIN
EXPDTA X-RAY DIFFRACTION
AUTHOR S.F.BELLON,H.JAYARAM,F.POY
REVDAT 3 28-FEB-24 4X2I 1 REMARK
REVDAT 2 30-MAR-16 4X2I 1 JRNL
REVDAT 1 11-NOV-15 4X2I 0
JRNL AUTH A.M.TAYLOR,R.G.VASWANI,V.S.GEHLING,M.C.HEWITT,Y.LEBLANC,
JRNL AUTH 2 J.E.AUDIA,S.BELLON,R.T.CUMMINGS,A.COTE,J.C.HARMANGE,
JRNL AUTH 3 H.JAYARAM,S.JOSHI,J.M.LORA,J.A.MERTZ,A.NEISS,E.PARDO,
JRNL AUTH 4 C.G.NASVESCHUK,F.POY,P.SANDY,J.W.SETSER,R.J.SIMS,Y.TANG,
JRNL AUTH 5 B.K.ALBRECHT
JRNL TITL DISCOVERY OF BENZOTRIAZOLO[4,3-D][1,4]DIAZEPINES AS ORALLY
JRNL TITL 2 ACTIVE INHIBITORS OF BET BROMODOMAINS.
JRNL REF ACS MED.CHEM.LETT. V. 7 145 2016
JRNL REFN ISSN 1948-5875
JRNL PMID 26985289
JRNL DOI 10.1021/ML500411H
REMARK 2
REMARK 2 RESOLUTION. 1.20 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.8.0069
REMARK 3 AUTHORS : MURSHUDOV,SKUBAK,LEBEDEV,PANNU,STEINER,
REMARK 3 : NICHOLLS,WINN,LONG,VAGIN
REMARK 3
REMARK 3 REFINEMENT TARGET : MAXIMUM LIKELIHOOD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.20
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 41.04
REMARK 3 DATA CUTOFF (SIGMA(F)) : NULL
REMARK 3 COMPLETENESS FOR RANGE (%) : 96.6
REMARK 3 NUMBER OF REFLECTIONS : 37915
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) : 0.141
REMARK 3 R VALUE (WORKING SET) : 0.138
REMARK 3 FREE R VALUE : 0.187
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT : 2004
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 20
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 1.20
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.23
REMARK 3 REFLECTION IN BIN (WORKING SET) : 2246
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 78.06
REMARK 3 BIN R VALUE (WORKING SET) : 0.2290
REMARK 3 BIN FREE R VALUE SET COUNT : 124
REMARK 3 BIN FREE R VALUE : 0.2740
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 1046
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 26
REMARK 3 SOLVENT ATOMS : 183
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 22.15
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 2.70000
REMARK 3 B22 (A**2) : -1.04000
REMARK 3 B33 (A**2) : -1.66000
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 OVERALL COORDINATE ERROR.
REMARK 3 ESU BASED ON R VALUE (A): 0.037
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.042
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.038
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 1.990
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.981
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.968
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 1131 ; 0.023 ; 0.020
REMARK 3 BOND LENGTHS OTHERS (A): 1070 ; 0.002 ; 0.020
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 1547 ; 2.061 ; 1.992
REMARK 3 BOND ANGLES OTHERS (DEGREES): 2474 ; 1.036 ; 3.005
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 131 ; 5.566 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 54 ;36.024 ;25.926
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 196 ;13.257 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 3 ;13.829 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 163 ; 0.133 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 1281 ; 0.011 ; 0.021
REMARK 3 GENERAL PLANES OTHERS (A): 260 ; 0.002 ; 0.020
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) OTHERS (A): NULL ; NULL ; NULL
REMARK 3 POTENTIAL METAL-ION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 POTENTIAL METAL-ION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY VDW REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY VDW OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY METAL-ION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY METAL-ION OTHERS (A): NULL ; NULL ; NULL
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT
REMARK 3 MAIN-CHAIN BOND REFINED ATOMS (A**2): 515 ; 3.104 ; 1.865
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): 516 ; 3.102 ; 1.866
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 646 ; 3.874 ; 2.800
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): 647 ; 3.872 ; 2.806
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 616 ; 3.258 ; 2.140
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): 617 ; 3.255 ; 2.139
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE OTHER ATOMS (A**2): 901 ; 4.062 ; 3.085
REMARK 3 LONG RANGE B REFINED ATOMS (A**2): 1493 ; 5.132 ;17.080
REMARK 3 LONG RANGE B OTHER ATOMS (A**2): 1494 ; 5.131 ;17.081
REMARK 3
REMARK 3 ANISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT
REMARK 3 RIGID-BOND RESTRAINTS (A**2): 2201 ; 5.855 ; 3.000
REMARK 3 SPHERICITY; FREE ATOMS (A**2): 50 ;28.368 ; 5.000
REMARK 3 SPHERICITY; BONDED ATOMS (A**2): 2299 ;11.188 ; 5.000
REMARK 3
REMARK 3 NCS RESTRAINTS STATISTICS
REMARK 3 NUMBER OF DIFFERENT NCS GROUPS : NULL
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : MASK
REMARK 3 PARAMETERS FOR MASK CALCULATION
REMARK 3 VDW PROBE RADIUS : 1.20
REMARK 3 ION PROBE RADIUS : 0.80
REMARK 3 SHRINKAGE RADIUS : 0.80
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: HYDROGENS HAVE BEEN ADDED IN THE RIDING
REMARK 3 POSITIONS
REMARK 4
REMARK 4 4X2I COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 02-DEC-14.
REMARK 100 THE DEPOSITION ID IS D_1000204960.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 23-JAN-12
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 8.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : APS
REMARK 200 BEAMLINE : 22-ID
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.00
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : MARMOSAIC 300 MM CCD
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : DENZO
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 39985
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.200
REMARK 200 RESOLUTION RANGE LOW (A) : 50.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 96.2
REMARK 200 DATA REDUNDANCY : 3.000
REMARK 200 R MERGE (I) : 0.07800
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 17.9900
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.20
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.24
REMARK 200 COMPLETENESS FOR SHELL (%) : NULL
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : 0.56300
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.290
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: AMORE
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 43.04
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.16
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: BRD4-BD1 PROTEIN AT 1MM, 2.682 M
REMARK 280 FORMATE, 10% GLYCEROL, 0.1 M TRIS-HCL PH 8.5, VAPOR DIFFUSION,
REMARK 280 SITTING DROP, TEMPERATURE 277K
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 16.95250
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 39.15700
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 24.09050
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 39.15700
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 16.95250
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 24.09050
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 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: 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 O HOH A 443 O HOH A 445 2.00
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 OD1 ASN A 162 O HOH A 313 4455 1.94
REMARK 500 O HOH A 395 O HOH A 446 3444 1.96
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: COVALENT BOND LENGTHS
REMARK 500
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT: (10X,I3,1X,2(A3,1X,A1,I4,A1,1X,A4,3X),1X,F6.3)
REMARK 500
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996
REMARK 500
REMARK 500 M RES CSSEQI ATM1 RES CSSEQI ATM2 DEVIATION
REMARK 500 ARG A 68 CZ ARG A 68 NH1 0.082
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: COVALENT BOND ANGLES
REMARK 500
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT: (10X,I3,1X,A3,1X,A1,I4,A1,3(1X,A4,2X),12X,F5.1)
REMARK 500
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996
REMARK 500
REMARK 500 M RES CSSEQI ATM1 ATM2 ATM3
REMARK 500 ARG A 68 NE - CZ - NH2 ANGL. DEV. = -7.0 DEGREES
REMARK 500 LYS A 76 CD - CE - NZ ANGL. DEV. = -17.6 DEGREES
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 117 53.58 38.91
REMARK 500
REMARK 500 REMARK: NULL
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 427 DISTANCE = 5.91 ANGSTROMS
REMARK 525 HOH A 430 DISTANCE = 6.19 ANGSTROMS
REMARK 525 HOH A 473 DISTANCE = 6.90 ANGSTROMS
REMARK 525 HOH A 474 DISTANCE = 9.07 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue FMT A 201
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 3X0 A 202
DBREF 4X2I A 42 166 UNP O60885 BRD4_HUMAN 42 166
SEQADV 4X2I GLY A 41 UNP O60885 EXPRESSION TAG
SEQRES 1 A 126 GLY SER THR ASN PRO PRO PRO PRO GLU THR SER ASN PRO
SEQRES 2 A 126 ASN LYS PRO LYS ARG GLN THR ASN GLN LEU GLN TYR LEU
SEQRES 3 A 126 LEU ARG VAL VAL LEU LYS THR LEU TRP LYS HIS GLN PHE
SEQRES 4 A 126 ALA TRP PRO PHE GLN GLN PRO VAL ASP ALA VAL LYS LEU
SEQRES 5 A 126 ASN LEU PRO ASP TYR TYR LYS ILE ILE LYS THR PRO MET
SEQRES 6 A 126 ASP MET GLY THR ILE LYS LYS ARG LEU GLU ASN ASN TYR
SEQRES 7 A 126 TYR TRP ASN ALA GLN GLU CYS ILE GLN ASP PHE ASN THR
SEQRES 8 A 126 MET PHE THR ASN CYS TYR ILE TYR ASN LYS PRO GLY ASP
SEQRES 9 A 126 ASP ILE VAL LEU MET ALA GLU ALA LEU GLU LYS LEU PHE
SEQRES 10 A 126 LEU GLN LYS ILE ASN GLU LEU PRO THR
HET FMT A 201 3
HET 3X0 A 202 23
HETNAM FMT FORMIC ACID
HETNAM 3X0 (4R)-6-(4-CHLOROPHENYL)-1,4-DIMETHYL-5,6-DIHYDRO-4H-[1,
HETNAM 2 3X0 2,4]TRIAZOLO[4,3-A][1,5]BENZODIAZEPINE
FORMUL 2 FMT C H2 O2
FORMUL 3 3X0 C18 H17 CL N4
FORMUL 4 HOH *183(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 ASN A 162 1 19
SITE 1 AC1 6 THR A 60 GLN A 62 ASN A 121 ALA A 122
SITE 2 AC1 6 HOH A 406 HOH A 445
SITE 1 AC2 11 PRO A 53 PRO A 82 LEU A 92 LEU A 94
SITE 2 AC2 11 LYS A 99 TYR A 139 ASN A 140 ASP A 145
SITE 3 AC2 11 ILE A 146 MET A 149 HOH A 404
CRYST1 33.905 48.181 78.314 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 0.029494 0.000000 0.000000 0.00000
SCALE2 0.000000 0.020755 0.000000 0.00000
SCALE3 0.000000 0.000000 0.012769 0.00000
(ATOM LINES ARE NOT SHOWN.)
END