HEADER SIGNALING PROTEIN 02-FEB-18 5Z9C
TITLE SOLUTION NMR STRUCTURES OF BRD4 FIRST BROMODOMAIN WITH SMALL COMPOUND
TITLE 2 MMQO
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BROMODOMAIN-CONTAINING PROTEIN 4;
COMPND 3 CHAIN: A;
COMPND 4 SYNONYM: PROTEIN HUNK1;
COMPND 5 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 BRD4, BROMODOMAIN, INHIBITOR, HIV, BET, MMQO, SIGNALING PROTEIN
EXPDTA SOLUTION NMR
NUMMDL 20
AUTHOR L.ZENG,M.-M.ZHOU
REVDAT 3 14-JUN-23 5Z9C 1 REMARK
REVDAT 2 16-MAY-18 5Z9C 1 JRNL
REVDAT 1 14-FEB-18 5Z9C 0
JRNL AUTH E.ABNER,M.STOSZKO,L.ZENG,H.C.CHEN,A.IZQUIERDO-BOULDSTRIDGE,
JRNL AUTH 2 T.KONUMA,E.ZORITA,E.FANUNZA,Q.ZHANG,T.MAHMOUDI,M.M.ZHOU,
JRNL AUTH 3 G.J.FILION,A.JORDAN
JRNL TITL A NEW QUINOLINE BRD4 INHIBITOR TARGETS A DISTINCT LATENT
JRNL TITL 2 HIV-1 RESERVOIR FOR REACTIVATION FROM OTHER "SHOCK" DRUGS.
JRNL REF J. VIROL. V. 92 2018
JRNL REFN ESSN 1098-5514
JRNL PMID 29343578
JRNL DOI 10.1128/JVI.02056-17
REMARK 2
REMARK 2 RESOLUTION. NOT APPLICABLE.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : ARIA
REMARK 3 AUTHORS : LINGE, O'DONOGHUE AND NILGES
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 5Z9C COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBJ ON 07-FEB-18.
REMARK 100 THE DEPOSITION ID IS D_1300006696.
REMARK 210
REMARK 210 EXPERIMENTAL DETAILS
REMARK 210 EXPERIMENT TYPE : NMR
REMARK 210 TEMPERATURE (KELVIN) : 298
REMARK 210 PH : 7.5
REMARK 210 IONIC STRENGTH : NULL
REMARK 210 PRESSURE : 1 ATM
REMARK 210 SAMPLE CONTENTS : 100 MM NACL, 10 MM SODIUM
REMARK 210 PHOSPHATE, 90% H2O/10% D2O
REMARK 210
REMARK 210 NMR EXPERIMENTS CONDUCTED : 3D 1H-15N NOESY; 3D HNCACB; 3D
REMARK 210 CBCA(CO)NH; 3D 13C NOESY; 3D 13
REMARK 210 NOESY AROMATIC
REMARK 210 SPECTROMETER FIELD STRENGTH : 800 MHZ; 900 MHZ
REMARK 210 SPECTROMETER MODEL : AVANCE
REMARK 210 SPECTROMETER MANUFACTURER : BRUKER
REMARK 210
REMARK 210 STRUCTURE DETERMINATION.
REMARK 210 SOFTWARE USED : CNS, NMRVIEW
REMARK 210 METHOD USED : SIMULATED ANNEALING
REMARK 210
REMARK 210 CONFORMERS, NUMBER CALCULATED : 200
REMARK 210 CONFORMERS, NUMBER SUBMITTED : 20
REMARK 210 CONFORMERS, SELECTION CRITERIA : STRUCTURES WITH THE LOWEST
REMARK 210 ENERGY
REMARK 210
REMARK 210 BEST REPRESENTATIVE CONFORMER IN THIS ENSEMBLE : 1
REMARK 210
REMARK 210 REMARK: NULL
REMARK 215
REMARK 215 NMR STUDY
REMARK 215 THE COORDINATES IN THIS ENTRY WERE GENERATED FROM SOLUTION
REMARK 215 NMR DATA. PROTEIN DATA BANK CONVENTIONS REQUIRE THAT
REMARK 215 CRYST1 AND SCALE RECORDS BE INCLUDED, BUT THE VALUES ON
REMARK 215 THESE RECORDS ARE MEANINGLESS.
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 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
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 HD13 ILE A 101 HB2 TYR A 139 1.13
REMARK 500 HG23 ILE A 126 HZ PHE A 157 1.25
REMARK 500 HD2 PHE A 79 HG2 MET A 149 1.33
REMARK 500 HE2 TYR A 97 HB2 MQO A 201 1.34
REMARK 500 O GLN A 64 H ARG A 68 1.50
REMARK 500 O VAL A 147 H GLU A 151 1.55
REMARK 500 O LEU A 153 H PHE A 157 1.59
REMARK 500 O ASP A 96 H ILE A 100 1.60
REMARK 500 OD2 ASP A 106 HG1 THR A 109 1.60
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 1 GLN A 59 88.35 -65.43
REMARK 500 1 ASN A 93 75.41 61.08
REMARK 500 1 THR A 103 87.33 -160.47
REMARK 500 1 ASN A 117 26.87 47.77
REMARK 500 1 PRO A 165 168.66 -49.54
REMARK 500 2 ASN A 93 68.90 63.22
REMARK 500 2 PRO A 165 177.51 -49.75
REMARK 500 3 ASN A 93 71.37 59.82
REMARK 500 3 PRO A 165 157.90 -41.13
REMARK 500 4 ASN A 93 71.60 57.86
REMARK 500 4 THR A 103 87.67 -160.01
REMARK 500 4 PRO A 142 109.97 -46.72
REMARK 500 4 PRO A 165 160.59 -46.98
REMARK 500 5 GLN A 59 72.45 -68.53
REMARK 500 5 ASN A 93 66.10 60.86
REMARK 500 5 THR A 103 92.76 -162.06
REMARK 500 5 PRO A 142 109.48 -46.83
REMARK 500 5 PRO A 165 164.70 -47.31
REMARK 500 6 ASN A 54 100.94 -160.38
REMARK 500 6 GLN A 59 81.28 -68.49
REMARK 500 6 THR A 103 87.73 -160.15
REMARK 500 6 PRO A 142 109.86 -44.49
REMARK 500 6 PRO A 165 176.84 -51.02
REMARK 500 7 ASN A 93 71.55 60.67
REMARK 500 7 THR A 103 87.68 -161.51
REMARK 500 7 PRO A 142 109.29 -47.38
REMARK 500 7 PRO A 165 164.29 -47.55
REMARK 500 8 ASN A 93 67.79 61.39
REMARK 500 8 LYS A 99 -60.96 -96.83
REMARK 500 8 THR A 103 85.40 -160.13
REMARK 500 8 ASN A 117 28.69 48.52
REMARK 500 8 PRO A 142 109.82 -48.74
REMARK 500 8 PRO A 165 171.80 -49.25
REMARK 500 9 GLN A 59 86.41 -69.52
REMARK 500 9 PRO A 142 109.96 -47.91
REMARK 500 9 PRO A 165 158.18 -46.18
REMARK 500 10 GLN A 59 82.71 -65.80
REMARK 500 10 ASN A 93 69.37 60.46
REMARK 500 10 LYS A 99 -61.48 -95.79
REMARK 500 10 THR A 103 88.20 -160.85
REMARK 500 10 PRO A 142 109.95 -45.75
REMARK 500 10 PRO A 165 174.42 -50.33
REMARK 500 11 ASN A 54 79.67 64.08
REMARK 500 11 GLN A 59 90.15 -69.93
REMARK 500 11 ASN A 93 66.34 60.18
REMARK 500 11 LYS A 99 -60.98 -97.37
REMARK 500 11 THR A 103 87.67 -161.18
REMARK 500 11 PRO A 142 109.05 -48.84
REMARK 500 11 PRO A 165 175.89 -50.45
REMARK 500 12 GLN A 59 75.19 -69.10
REMARK 500
REMARK 500 THIS ENTRY HAS 89 RAMACHANDRAN OUTLIERS.
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 MQO A 201
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 36163 RELATED DB: BMRB
REMARK 900 SOLUTION NMR STRUCTURES OF BRD4 FIRST BROMODOMAIN WITH SMALL
REMARK 900 COMPOUND MMQO
DBREF 5Z9C A 53 168 UNP O60885 BRD4_HUMAN 53 168
SEQRES 1 A 116 PRO ASN LYS PRO LYS ARG GLN THR ASN GLN LEU GLN TYR
SEQRES 2 A 116 LEU LEU ARG VAL VAL LEU LYS THR LEU TRP LYS HIS GLN
SEQRES 3 A 116 PHE ALA TRP PRO PHE GLN GLN PRO VAL ASP ALA VAL LYS
SEQRES 4 A 116 LEU ASN LEU PRO ASP TYR TYR LYS ILE ILE LYS THR PRO
SEQRES 5 A 116 MET ASP MET GLY THR ILE LYS LYS ARG LEU GLU ASN ASN
SEQRES 6 A 116 TYR TYR TRP ASN ALA GLN GLU CYS ILE GLN ASP PHE ASN
SEQRES 7 A 116 THR MET PHE THR ASN CYS TYR ILE TYR ASN LYS PRO GLY
SEQRES 8 A 116 ASP ASP ILE VAL LEU MET ALA GLU ALA LEU GLU LYS LEU
SEQRES 9 A 116 PHE LEU GLN LYS ILE ASN GLU LEU PRO THR GLU GLU
HET MQO A 201 25
HETNAM MQO 8-METHOXY-6-METHYLQUINOLIN-4(1H)-ONE
FORMUL 2 MQO C11 H11 N O2
HELIX 1 AA1 GLN A 59 VAL A 69 1 11
HELIX 2 AA2 VAL A 69 LYS A 76 1 8
HELIX 3 AA3 ALA A 80 GLN A 85 1 6
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 9 TRP A 81 PRO A 82 VAL A 87 LEU A 92
SITE 2 AC1 9 LEU A 94 TYR A 97 TYR A 139 ASN A 140
SITE 3 AC1 9 ILE A 146
CRYST1 1.000 1.000 1.000 90.00 90.00 90.00 P 1 1
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 1.000000 0.000000 0.000000 0.00000
SCALE2 0.000000 1.000000 0.000000 0.00000
SCALE3 0.000000 0.000000 1.000000 0.00000
MODEL 1
(ATOM LINES ARE NOT SHOWN.)
END