HEADER TRANSCRIPTION 21-NOV-16 5MGL
TITLE CRYSTAL STRUCTURE OF BAZ2A BROMODOMAIN IN COMPLEX WITH 4-
TITLE 2 CHLOROPYRIDINE DERIVATIVE 3
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BROMODOMAIN ADJACENT TO ZINC FINGER DOMAIN PROTEIN 2A;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: BROMODOMAIN, UNP RESIDUES 1796-1898;
COMPND 5 SYNONYM: TRANSCRIPTION TERMINATION FACTOR I-INTERACTING PROTEIN 5,
COMPND 6 TIP5,HWALP3;
COMPND 7 ENGINEERED: YES;
COMPND 8 OTHER_DETAILS: FIRST TWO RESIDUES SM DERIVE FROM THE EXPRESSION TAG
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 GENE: BAZ2A, KIAA0314, TIP5;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS FOUR HELICAL BUNDLE, TRANSCRIPTION
EXPDTA X-RAY DIFFRACTION
AUTHOR G.LOLLI,D.SPILIOTOPOULOS,A.CAFLISCH
REVDAT 3 17-JAN-24 5MGL 1 REMARK
REVDAT 2 06-SEP-17 5MGL 1 JRNL
REVDAT 1 12-APR-17 5MGL 0
JRNL AUTH D.SPILIOTOPOULOS,E.C.WAMHOFF,G.LOLLI,C.RADEMACHER,A.CAFLISCH
JRNL TITL DISCOVERY OF BAZ2A BROMODOMAIN LIGANDS.
JRNL REF EUR J MED CHEM V. 139 564 2017
JRNL REFN ISSN 1768-3254
JRNL PMID 28837921
JRNL DOI 10.1016/J.EJMECH.2017.08.028
REMARK 2
REMARK 2 RESOLUTION. 2.65 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) : 2.65
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 27.06
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 1.330
REMARK 3 COMPLETENESS FOR RANGE (%) : 100.0
REMARK 3 NUMBER OF REFLECTIONS : 5172
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.216
REMARK 3 R VALUE (WORKING SET) : 0.213
REMARK 3 FREE R VALUE : 0.253
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.320
REMARK 3 FREE R VALUE TEST SET COUNT : 275
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 27.0645 - 3.3386 1.00 2498 125 0.1883 0.2353
REMARK 3 2 3.3386 - 2.6507 1.00 2399 150 0.2587 0.2772
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) : 0.300
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 22.990
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 35.18
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 : 0.002 867
REMARK 3 ANGLE : 0.611 1168
REMARK 3 CHIRALITY : 0.021 117
REMARK 3 PLANARITY : 0.004 154
REMARK 3 DIHEDRAL : 12.755 322
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : 4
REMARK 3 TLS GROUP : 1
REMARK 3 SELECTION: CHAIN 'A' AND (RESID 1799 THROUGH 1810 )
REMARK 3 ORIGIN FOR THE GROUP (A): 61.1671 22.5746 7.2298
REMARK 3 T TENSOR
REMARK 3 T11: 0.1566 T22: 0.2052
REMARK 3 T33: 0.3286 T12: -0.0777
REMARK 3 T13: 0.0866 T23: 0.0426
REMARK 3 L TENSOR
REMARK 3 L11: 0.0879 L22: 0.0119
REMARK 3 L33: 0.0458 L12: -0.0100
REMARK 3 L13: 0.0391 L23: 0.0076
REMARK 3 S TENSOR
REMARK 3 S11: -0.0895 S12: 0.0364 S13: -0.0271
REMARK 3 S21: -0.0086 S22: -0.0363 S23: -0.0629
REMARK 3 S31: 0.1198 S32: -0.0300 S33: -0.1113
REMARK 3 TLS GROUP : 2
REMARK 3 SELECTION: CHAIN 'A' AND (RESID 1811 THROUGH 1839 )
REMARK 3 ORIGIN FOR THE GROUP (A): 60.2700 36.7737 -6.4937
REMARK 3 T TENSOR
REMARK 3 T11: 0.2047 T22: 0.4271
REMARK 3 T33: 0.2561 T12: -0.0501
REMARK 3 T13: 0.0216 T23: -0.0362
REMARK 3 L TENSOR
REMARK 3 L11: 0.0295 L22: 0.2662
REMARK 3 L33: 0.0634 L12: -0.0489
REMARK 3 L13: -0.0108 L23: 0.1276
REMARK 3 S TENSOR
REMARK 3 S11: 0.0123 S12: 0.1044 S13: -0.1313
REMARK 3 S21: -0.1695 S22: 0.1152 S23: 0.0373
REMARK 3 S31: -0.1154 S32: -0.2603 S33: -0.0007
REMARK 3 TLS GROUP : 3
REMARK 3 SELECTION: CHAIN 'A' AND (RESID 1840 THROUGH 1872 )
REMARK 3 ORIGIN FOR THE GROUP (A): 65.5570 26.1121 -2.4726
REMARK 3 T TENSOR
REMARK 3 T11: 0.1818 T22: 0.1930
REMARK 3 T33: 0.2191 T12: -0.0755
REMARK 3 T13: 0.1417 T23: -0.0813
REMARK 3 L TENSOR
REMARK 3 L11: 0.3441 L22: 0.4436
REMARK 3 L33: 0.5459 L12: 0.1827
REMARK 3 L13: 0.1904 L23: -0.2153
REMARK 3 S TENSOR
REMARK 3 S11: -0.2292 S12: 0.2039 S13: -0.2016
REMARK 3 S21: -0.0910 S22: -0.0609 S23: -0.2460
REMARK 3 S31: -0.0171 S32: 0.0015 S33: -0.3772
REMARK 3 TLS GROUP : 4
REMARK 3 SELECTION: CHAIN 'A' AND (RESID 1873 THROUGH 1898 )
REMARK 3 ORIGIN FOR THE GROUP (A): 67.5308 35.0834 7.0285
REMARK 3 T TENSOR
REMARK 3 T11: 0.0443 T22: 0.2255
REMARK 3 T33: 0.0857 T12: -0.0341
REMARK 3 T13: -0.0010 T23: 0.0109
REMARK 3 L TENSOR
REMARK 3 L11: 0.1239 L22: 0.5256
REMARK 3 L33: 0.2256 L12: 0.1173
REMARK 3 L13: 0.0328 L23: 0.0829
REMARK 3 S TENSOR
REMARK 3 S11: 0.0968 S12: -0.3111 S13: 0.0586
REMARK 3 S21: 0.2520 S22: 0.0679 S23: -0.0113
REMARK 3 S31: 0.0202 S32: -0.0490 S33: 0.0300
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 5MGL COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 21-NOV-16.
REMARK 100 THE DEPOSITION ID IS D_1200002440.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 05-OCT-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) : 1.00
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 : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : AIMLESS 0.3.11
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 5180
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.650
REMARK 200 RESOLUTION RANGE LOW (A) : 27.063
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.9
REMARK 200 DATA REDUNDANCY : 9.600
REMARK 200 R MERGE (I) : 0.26800
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 7.0000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.65
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.78
REMARK 200 COMPLETENESS FOR SHELL (%) : 100.0
REMARK 200 DATA REDUNDANCY IN SHELL : 8.20
REMARK 200 R MERGE FOR SHELL (I) : 0.93600
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: 4LZ2
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 64.81
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.50
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 20% PEG3350, 0.2 M MGCL2, PH 7.5,
REMARK 280 VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 277K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 31 2 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -Y,X-Y,Z+1/3
REMARK 290 3555 -X+Y,-X,Z+2/3
REMARK 290 4555 Y,X,-Z
REMARK 290 5555 X-Y,-Y,-Z+2/3
REMARK 290 6555 -X,-X+Y,-Z+1/3
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 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 2 0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 10.94667
REMARK 290 SMTRY1 3 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 3 -0.866025 -0.500000 0.000000 0.00000
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 21.89333
REMARK 290 SMTRY1 4 -0.500000 0.866025 0.000000 0.00000
REMARK 290 SMTRY2 4 0.866025 0.500000 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 0.00000
REMARK 290 SMTRY2 5 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 5 0.000000 0.000000 -1.000000 21.89333
REMARK 290 SMTRY1 6 -0.500000 -0.866025 0.000000 0.00000
REMARK 290 SMTRY2 6 -0.866025 0.500000 0.000000 0.00000
REMARK 290 SMTRY3 6 0.000000 0.000000 -1.000000 10.94667
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: 6070 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 1794
REMARK 465 MET A 1795
REMARK 465 HIS A 1796
REMARK 465 SER A 1797
REMARK 465 ASP A 1798
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 A2051 DISTANCE = 6.16 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 7MU A 1901
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 5MGG RELATED DB: PDB
REMARK 900 5MGG CONTAINS THE SAME LIGAND COMPLEXED WITH A DIFFERENT
REMARK 900 BROMODOMAIN (BAZ2B).
REMARK 900 RELATED ID: 5MGJ RELATED DB: PDB
REMARK 900 5MGJ CONTAINS THE SAME PROTEIN COMPLEXED WITH A DIFFERENT FRAGMENT.
REMARK 900 RELATED ID: 5MGK RELATED DB: PDB
REMARK 900 5MGK CONTAINS THE SAME PROTEIN COMPLEXED WITH A DIFFERENT FRAGMENT.
DBREF 5MGL A 1796 1898 UNP Q9UIF9 BAZ2A_HUMAN 1796 1898
SEQADV 5MGL SER A 1794 UNP Q9UIF9 EXPRESSION TAG
SEQADV 5MGL MET A 1795 UNP Q9UIF9 EXPRESSION TAG
SEQRES 1 A 105 SER MET HIS SER ASP LEU THR PHE CYS GLU ILE ILE LEU
SEQRES 2 A 105 MET GLU MET GLU SER HIS ASP ALA ALA TRP PRO PHE LEU
SEQRES 3 A 105 GLU PRO VAL ASN PRO ARG LEU VAL SER GLY TYR ARG ARG
SEQRES 4 A 105 ILE ILE LYS ASN PRO MET ASP PHE SER THR MET ARG GLU
SEQRES 5 A 105 ARG LEU LEU ARG GLY GLY TYR THR SER SER GLU GLU PHE
SEQRES 6 A 105 ALA ALA ASP ALA LEU LEU VAL PHE ASP ASN CYS GLN THR
SEQRES 7 A 105 PHE ASN GLU ASP ASP SER GLU VAL GLY LYS ALA GLY HIS
SEQRES 8 A 105 ILE MET ARG ARG PHE PHE GLU SER ARG TRP GLU GLU PHE
SEQRES 9 A 105 TYR
HET 7MU A1901 11
HETNAM 7MU 4-CHLORANYL-~{N}-METHYL-PYRIDINE-2-CARBOXAMIDE
FORMUL 2 7MU C7 H7 CL N2 O
FORMUL 3 HOH *51(H2 O)
HELIX 1 AA1 LEU A 1799 SER A 1811 1 13
HELIX 2 AA2 HIS A 1812 TRP A 1816 5 5
HELIX 3 AA3 GLY A 1829 ILE A 1834 1 6
HELIX 4 AA4 ASP A 1839 GLY A 1850 1 12
HELIX 5 AA5 SER A 1854 ASN A 1873 1 20
HELIX 6 AA6 SER A 1877 TYR A 1898 1 22
SITE 1 AC1 7 PRO A1817 PHE A1818 VAL A1822 TYR A1830
SITE 2 AC1 7 PHE A1872 ASN A1873 HOH A2003
CRYST1 95.550 95.550 32.840 90.00 90.00 120.00 P 31 2 1 6
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 0.010466 0.006042 0.000000 0.00000
SCALE2 0.000000 0.012085 0.000000 0.00000
SCALE3 0.000000 0.000000 0.030450 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
