HEADER TRANSCRIPTION 09-JUN-16 5L96
TITLE CRYSTAL STRUCTURE OF BAZ2B BROMODOMAIN IN COMPLEX WITH 3-AMINO-2-
TITLE 2 METHYLPYRIDINE DERIVATIVE 1
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BROMODOMAIN ADJACENT TO ZINC FINGER DOMAIN PROTEIN 2B;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: BROMODOMAIN (RESIDUES 2054-2168);
COMPND 5 SYNONYM: HWALP4;
COMPND 6 ENGINEERED: YES;
COMPND 7 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 GENE: BAZ2B, KIAA1476;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS FOUR HELICAL BUNDLE, TRANSCRIPTION
EXPDTA X-RAY DIFFRACTION
AUTHOR G.LOLLI,J.-R.MARCHAND,A.CAFLISCH
REVDAT 3 10-JAN-24 5L96 1 REMARK
REVDAT 2 21-DEC-16 5L96 1 JRNL
REVDAT 1 26-OCT-16 5L96 0
JRNL AUTH J.R.MARCHAND,G.LOLLI,A.CAFLISCH
JRNL TITL DERIVATIVES OF 3-AMINO-2-METHYLPYRIDINE AS BAZ2B BROMODOMAIN
JRNL TITL 2 LIGANDS: IN SILICO DISCOVERY AND IN CRYSTALLO VALIDATION.
JRNL REF J. MED. CHEM. V. 59 9919 2016
JRNL REFN ISSN 1520-4804
JRNL PMID 27731638
JRNL DOI 10.1021/ACS.JMEDCHEM.6B01258
REMARK 2
REMARK 2 RESOLUTION. 2.15 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX
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) : 2.15
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 33.43
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 1.340
REMARK 3 COMPLETENESS FOR RANGE (%) : 98.2
REMARK 3 NUMBER OF REFLECTIONS : 12623
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.192
REMARK 3 R VALUE (WORKING SET) : 0.190
REMARK 3 FREE R VALUE : 0.228
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 4.980
REMARK 3 FREE R VALUE TEST SET COUNT : 629
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 33.4331 - 3.4124 0.97 3092 146 0.1632 0.1987
REMARK 3 2 3.4124 - 2.7089 0.99 3019 160 0.2091 0.2294
REMARK 3 3 2.7089 - 2.3666 0.98 2950 155 0.2213 0.2650
REMARK 3 4 2.3666 - 2.1502 0.99 2933 168 0.2594 0.3231
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) : 0.190
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 29.340
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 36.08
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 54.56
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 : 0.005 998
REMARK 3 ANGLE : 0.932 1344
REMARK 3 CHIRALITY : 0.033 144
REMARK 3 PLANARITY : 0.004 169
REMARK 3 DIHEDRAL : 15.889 385
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 5L96 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 09-JUN-16.
REMARK 100 THE DEPOSITION ID IS D_1200000362.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 20-FEB-16
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 7.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : ELETTRA
REMARK 200 BEAMLINE : 5.2R
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 2M
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS, XDS
REMARK 200 DATA SCALING SOFTWARE : AIMLESS
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 12723
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.150
REMARK 200 RESOLUTION RANGE LOW (A) : 42.480
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.3
REMARK 200 DATA REDUNDANCY : 5.100
REMARK 200 R MERGE (I) : 0.06900
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 13.0000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.15
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.22
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.7
REMARK 200 DATA REDUNDANCY IN SHELL : 5.30
REMARK 200 R MERGE FOR SHELL (I) : 0.43500
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: 4IR5
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 70.99
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 4.24
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PEG500MME (20%), PEG1000 (2%), PEG3350
REMARK 280 (2%), PEG20000 (10%), MPD (2%), PH 7.5, VAPOR DIFFUSION, SITTING
REMARK 280 DROP, TEMPERATURE 277K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: C 2 2 21
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,-Y,Z+1/2
REMARK 290 3555 -X,Y,-Z+1/2
REMARK 290 4555 X,-Y,-Z
REMARK 290 5555 X+1/2,Y+1/2,Z
REMARK 290 6555 -X+1/2,-Y+1/2,Z+1/2
REMARK 290 7555 -X+1/2,Y+1/2,-Z+1/2
REMARK 290 8555 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 28.95050
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 28.95050
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 5 1.000000 0.000000 0.000000 40.94200
REMARK 290 SMTRY2 5 0.000000 1.000000 0.000000 48.40250
REMARK 290 SMTRY3 5 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 6 -1.000000 0.000000 0.000000 40.94200
REMARK 290 SMTRY2 6 0.000000 -1.000000 0.000000 48.40250
REMARK 290 SMTRY3 6 0.000000 0.000000 1.000000 28.95050
REMARK 290 SMTRY1 7 -1.000000 0.000000 0.000000 40.94200
REMARK 290 SMTRY2 7 0.000000 1.000000 0.000000 48.40250
REMARK 290 SMTRY3 7 0.000000 0.000000 -1.000000 28.95050
REMARK 290 SMTRY1 8 1.000000 0.000000 0.000000 40.94200
REMARK 290 SMTRY2 8 0.000000 -1.000000 0.000000 48.40250
REMARK 290 SMTRY3 8 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 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 150 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 7820 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: 2.0 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 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 A1970 31.72 -77.67
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 6RZ A 2001
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue EDO A 2002
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 5E9K RELATED DB: PDB
REMARK 900 5E9K CONTAINS THE SAME PROTEIN COMPLEXED WITH A SIMILAR HEAD GROUP
REMARK 900 RELATED ID: 5L8T RELATED DB: PDB
REMARK 900 5L8T CONTAINS THE SAME PROTEIN COMPLEXED WITH A SIMILAR COMPOUND
REMARK 900 RELATED ID: 5L8U RELATED DB: PDB
REMARK 900 5L8U CONTAINS THE SAME PROTEIN COMPLEXED WITH A SIMILAR COMPOUND
DBREF 5L96 A 1858 1971 UNP Q9UIF8 BAZ2B_HUMAN 1858 1971
SEQADV 5L96 SER A 1856 UNP Q9UIF8 EXPRESSION TAG
SEQADV 5L96 MET A 1857 UNP Q9UIF8 EXPRESSION TAG
SEQRES 1 A 116 SER MET SER VAL LYS LYS PRO LYS ARG ASP ASP SER LYS
SEQRES 2 A 116 ASP LEU ALA LEU CYS SER MET ILE LEU THR GLU MET GLU
SEQRES 3 A 116 THR HIS GLU ASP ALA TRP PRO PHE LEU LEU PRO VAL ASN
SEQRES 4 A 116 LEU LYS LEU VAL PRO GLY TYR LYS LYS VAL ILE LYS LYS
SEQRES 5 A 116 PRO MET ASP PHE SER THR ILE ARG GLU LYS LEU SER SER
SEQRES 6 A 116 GLY GLN TYR PRO ASN LEU GLU THR PHE ALA LEU ASP VAL
SEQRES 7 A 116 ARG LEU VAL PHE ASP ASN CYS GLU THR PHE ASN GLU ASP
SEQRES 8 A 116 ASP SER ASP ILE GLY ARG ALA GLY HIS ASN MET ARG LYS
SEQRES 9 A 116 TYR PHE GLU LYS LYS TRP THR ASP THR PHE LYS VAL
HET 6RZ A2001 15
HET EDO A2002 4
HETNAM 6RZ 2-METHYL-~{N}-[(2~{R})-1-METHYLSULFONYLPROPAN-2-
HETNAM 2 6RZ YL]PYRIDIN-3-AMINE
HETNAM EDO 1,2-ETHANEDIOL
HETSYN EDO ETHYLENE GLYCOL
FORMUL 2 6RZ C10 H16 N2 O2 S
FORMUL 3 EDO C2 H6 O2
FORMUL 4 HOH *66(H2 O)
HELIX 1 AA1 LYS A 1868 THR A 1882 1 15
HELIX 2 AA2 HIS A 1883 TRP A 1887 5 5
HELIX 3 AA3 GLY A 1900 ILE A 1905 1 6
HELIX 4 AA4 ASP A 1910 SER A 1920 1 11
HELIX 5 AA5 ASN A 1925 ASN A 1944 1 20
HELIX 6 AA6 SER A 1948 PHE A 1969 1 22
SITE 1 AC1 10 PRO A1888 VAL A1893 ASN A1894 LEU A1897
SITE 2 AC1 10 VAL A1898 TYR A1901 PHE A1943 ASN A1944
SITE 3 AC1 10 EDO A2002 HOH A2108
SITE 1 AC2 2 PRO A1899 6RZ A2001
CRYST1 81.884 96.805 57.901 90.00 90.00 90.00 C 2 2 21 8
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 0.012212 0.000000 0.000000 0.00000
SCALE2 0.000000 0.010330 0.000000 0.00000
SCALE3 0.000000 0.000000 0.017271 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
