HEADER TRANSCRIPTION 23-MAY-17 5O3C
TITLE HUMAN BRD2(BD2) MUTANT IN COMPLEX WITH 9-ME
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BROMODOMAIN-CONTAINING PROTEIN 2;
COMPND 3 CHAIN: A;
COMPND 4 SYNONYM: O27.1.1,REALLY INTERESTING NEW GENE 3 PROTEIN;
COMPND 5 ENGINEERED: YES;
COMPND 6 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: BRD2, KIAA9001, RING3;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 511693;
SOURCE 8 EXPRESSION_SYSTEM_PLASMID: PNIC28-BSA4
KEYWDS THE BROMODOMAIN AND EXTRA-TERMINAL DOMAIN (BET) FAMILY CHROMATIN
KEYWDS 2 BINDING PROTEIN, TRANSCRIPTION
EXPDTA X-RAY DIFFRACTION
AUTHOR A.C.RUNCIE,K.-H.CHAN,A.CIULLI
REVDAT 3 17-JAN-24 5O3C 1 REMARK
REVDAT 2 16-MAY-18 5O3C 1 JRNL
REVDAT 1 14-FEB-18 5O3C 0
JRNL AUTH A.C.RUNCIE,M.ZENGERLE,K.H.CHAN,A.TESTA,L.VAN BEURDEN,
JRNL AUTH 2 M.G.J.BAUD,O.EPEMOLU,L.C.J.ELLIS,K.D.READ,V.COULTHARD,
JRNL AUTH 3 A.BRIEN,A.CIULLI
JRNL TITL OPTIMIZATION OF A "BUMP-AND-HOLE" APPROACH TO
JRNL TITL 2 ALLELE-SELECTIVE BET BROMODOMAIN INHIBITION.
JRNL REF CHEM SCI V. 9 2452 2018
JRNL REFN ISSN 2041-6520
JRNL PMID 29732121
JRNL DOI 10.1039/C7SC02536J
REMARK 2
REMARK 2 RESOLUTION. 1.60 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : PHENIX 1.9_1692
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 : ML
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 1.60
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 31.85
REMARK 3 MIN(FOBS/SIGMA_FOBS) : 1.340
REMARK 3 COMPLETENESS FOR RANGE (%) : 99.5
REMARK 3 NUMBER OF REFLECTIONS : 16283
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 R VALUE (WORKING + TEST SET) : 0.164
REMARK 3 R VALUE (WORKING SET) : 0.162
REMARK 3 FREE R VALUE : 0.194
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 4.940
REMARK 3 FREE R VALUE TEST SET COUNT : 804
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 31.8583 - 2.9071 0.99 2710 135 0.1456 0.1561
REMARK 3 2 2.9071 - 2.3077 1.00 2616 132 0.1636 0.2051
REMARK 3 3 2.3077 - 2.0160 1.00 2558 133 0.1538 0.2091
REMARK 3 4 2.0160 - 1.8317 0.99 2551 140 0.1767 0.2202
REMARK 3 5 1.8317 - 1.7004 1.00 2552 116 0.1914 0.2503
REMARK 3 6 1.7004 - 1.6002 1.00 2492 148 0.2158 0.2434
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : FLAT BULK SOLVENT MODEL
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) : 0.150
REMARK 3 PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 17.970
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : NULL
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 : 0.007 984
REMARK 3 ANGLE : 1.081 1327
REMARK 3 CHIRALITY : 0.038 133
REMARK 3 PLANARITY : 0.005 168
REMARK 3 DIHEDRAL : 11.260 361
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 5O3C COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 24-MAY-17.
REMARK 100 THE DEPOSITION ID IS D_1200005102.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 24-APR-16
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 : DIAMOND
REMARK 200 BEAMLINE : I02
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.9795
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : PIXEL
REMARK 200 DETECTOR MANUFACTURER : DECTRIS PILATUS 6M-F
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : XDS
REMARK 200 DATA SCALING SOFTWARE : AIMLESS
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 16285
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.600
REMARK 200 RESOLUTION RANGE LOW (A) : 31.850
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.5
REMARK 200 DATA REDUNDANCY : 4.300
REMARK 200 R MERGE (I) : 0.11110
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 7.6700
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.60
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.66
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.6
REMARK 200 DATA REDUNDANCY IN SHELL : 4.20
REMARK 200 R MERGE FOR SHELL (I) : 0.56270
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 2.040
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: PHENIX
REMARK 200 STARTING MODEL: 4QEU
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 44.80
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.23
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.2M TRIS PH 8.5 60% PENTAERYTHRITOL
REMARK 280 PROPOXYLATE (5/4 PO/OH), VAPOR DIFFUSION, SITTING DROP,
REMARK 280 TEMPERATURE 293K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 2 21 21
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,Y+1/2,-Z+1/2
REMARK 290 4555 -X,-Y+1/2,Z+1/2
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 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 26.04100
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 35.89450
REMARK 290 SMTRY1 4 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 26.04100
REMARK 290 SMTRY3 4 0.000000 0.000000 1.000000 35.89450
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: 110 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 6620 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -6.0 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 375
REMARK 375 SPECIAL POSITION
REMARK 375 THE FOLLOWING ATOMS ARE FOUND TO BE WITHIN 0.15 ANGSTROMS
REMARK 375 OF A SYMMETRY RELATED ATOM AND ARE ASSUMED TO BE ON SPECIAL
REMARK 375 POSITIONS.
REMARK 375
REMARK 375 ATOM RES CSSEQI
REMARK 375 CL CL A 502 LIES ON A SPECIAL POSITION.
REMARK 375 HOH A 799 LIES ON A SPECIAL POSITION.
REMARK 375 HOH A 811 LIES ON A SPECIAL POSITION.
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 342
REMARK 465 MET A 343
REMARK 465 GLY A 344
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 616 O HOH A 755 2.11
REMARK 500 O HOH A 623 O HOH A 682 2.12
REMARK 500 O HOH A 711 O HOH A 780 2.14
REMARK 500 O HOH A 672 O HOH A 766 2.15
REMARK 500 O HOH A 809 O HOH A 812 2.16
REMARK 500 O HOH A 742 O HOH A 761 2.19
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 O HOH A 601 O HOH A 714 1655 2.11
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 809 DISTANCE = 6.27 ANGSTROMS
REMARK 525 HOH A 810 DISTANCE = 6.34 ANGSTROMS
REMARK 525 HOH A 811 DISTANCE = 6.40 ANGSTROMS
REMARK 525 HOH A 812 DISTANCE = 6.55 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue 9J2 A 501
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue CL A 502
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: binding site for residue DQW A 503
DBREF 5O3C A 344 455 UNP P25440 BRD2_HUMAN 344 455
SEQADV 5O3C SER A 342 UNP P25440 EXPRESSION TAG
SEQADV 5O3C MET A 343 UNP P25440 EXPRESSION TAG
SEQADV 5O3C VAL A 383 UNP P25440 LEU 383 ENGINEERED MUTATION
SEQRES 1 A 114 SER MET GLY LYS LEU SER GLU GLN LEU LYS HIS CYS ASN
SEQRES 2 A 114 GLY ILE LEU LYS GLU LEU LEU SER LYS LYS HIS ALA ALA
SEQRES 3 A 114 TYR ALA TRP PRO PHE TYR LYS PRO VAL ASP ALA SER ALA
SEQRES 4 A 114 LEU GLY VAL HIS ASP TYR HIS ASP ILE ILE LYS HIS PRO
SEQRES 5 A 114 MET ASP LEU SER THR VAL LYS ARG LYS MET GLU ASN ARG
SEQRES 6 A 114 ASP TYR ARG ASP ALA GLN GLU PHE ALA ALA ASP VAL ARG
SEQRES 7 A 114 LEU MET PHE SER ASN CYS TYR LYS TYR ASN PRO PRO ASP
SEQRES 8 A 114 HIS ASP VAL VAL ALA MET ALA ARG LYS LEU GLN ASP VAL
SEQRES 9 A 114 PHE GLU PHE ARG TYR ALA LYS MET PRO ASP
HET 9J2 A 501 51
HET CL A 502 1
HET DQW A 503 23
HETNAM 9J2 METHYL (2~{R})-2-[(4~{S})-6-(4-CHLOROPHENYL)-9-METHOXY-
HETNAM 2 9J2 1-METHYL-4~{H}-[1,2,4]TRIAZOLO[4,3-A][1,
HETNAM 3 9J2 4]BENZODIAZEPIN-4-YL]PROPANOATE
HETNAM CL CHLORIDE ION
HETNAM DQW (2~{S})-1-[(2~{S})-2-OXIDANYLPROPOXY]PROPAN-2-OL
FORMUL 2 9J2 C22 H21 CL N4 O3
FORMUL 3 CL CL 1-
FORMUL 4 DQW C6 H14 O3
FORMUL 5 HOH *212(H2 O)
HELIX 1 AA1 SER A 347 LEU A 361 1 15
HELIX 2 AA2 SER A 362 LYS A 364 5 3
HELIX 3 AA3 HIS A 365 TRP A 370 1 6
HELIX 4 AA4 PRO A 371 TYR A 373 5 3
HELIX 5 AA5 ASP A 377 GLY A 382 1 6
HELIX 6 AA6 ASP A 385 ILE A 390 1 6
HELIX 7 AA7 ASP A 395 ASN A 405 1 11
HELIX 8 AA8 ASP A 410 ASN A 429 1 20
HELIX 9 AA9 HIS A 433 ALA A 451 1 19
SITE 1 AC1 10 LYS A 345 PRO A 371 PHE A 372 VAL A 383
SITE 2 AC1 10 ASN A 429 VAL A 435 HOH A 613 HOH A 620
SITE 3 AC1 10 HOH A 682 HOH A 688
SITE 1 AC2 2 ARG A 419 HOH A 636
SITE 1 AC3 4 TYR A 426 ARG A 440 ASP A 444 PHE A 448
CRYST1 31.852 52.082 71.789 90.00 90.00 90.00 P 2 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 0.031395 0.000000 0.000000 0.00000
SCALE2 0.000000 0.019200 0.000000 0.00000
SCALE3 0.000000 0.000000 0.013930 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
