[English] 日本語
Yorodumi
- PDB-7mr7: Crystal structure of the first bromodomain (BD1) of human BRD4 bo... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7mr7
TitleCrystal structure of the first bromodomain (BD1) of human BRD4 bound to GXH-II-075
ComponentsBromodomain-containing protein 4
KeywordsGENE REGULATION / Bromosporine / BRD4 / BRD / BET
Function / homology
Function and homology information


RNA polymerase II C-terminal domain binding / negative regulation of DNA damage checkpoint / P-TEFb complex binding / negative regulation by host of viral transcription / positive regulation of T-helper 17 cell lineage commitment / positive regulation of G2/M transition of mitotic cell cycle / RNA polymerase II CTD heptapeptide repeat kinase activity / histone reader activity / condensed nuclear chromosome / positive regulation of transcription elongation by RNA polymerase II ...RNA polymerase II C-terminal domain binding / negative regulation of DNA damage checkpoint / P-TEFb complex binding / negative regulation by host of viral transcription / positive regulation of T-helper 17 cell lineage commitment / positive regulation of G2/M transition of mitotic cell cycle / RNA polymerase II CTD heptapeptide repeat kinase activity / histone reader activity / condensed nuclear chromosome / positive regulation of transcription elongation by RNA polymerase II / transcription coregulator activity / lysine-acetylated histone binding / p53 binding / chromosome / regulation of inflammatory response / positive regulation of canonical NF-kappaB signal transduction / Potential therapeutics for SARS / transcription coactivator activity / transcription cis-regulatory region binding / chromatin remodeling / DNA damage response / chromatin binding / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / enzyme binding / positive regulation of transcription by RNA polymerase II / nucleoplasm / nucleus
Similarity search - Function
Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / Brdt, bromodomain, repeat II / Brdt, bromodomain, repeat I / NET domain superfamily / NET domain profile. / : / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain, conserved site ...Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / Brdt, bromodomain, repeat II / Brdt, bromodomain, repeat I / NET domain superfamily / NET domain profile. / : / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily
Similarity search - Domain/homology
Chem-ZN1 / Bromodomain-containing protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.4 Å
AuthorsChan, A. / Schonbrunn, E.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD)1U54HD093540 United States
CitationJournal: J.Med.Chem. / Year: 2022
Title: Bivalent BET Bromodomain Inhibitors Confer Increased Potency and Selectivity for BRDT via Protein Conformational Plasticity.
Authors: Guan, X. / Cheryala, N. / Karim, R.M. / Chan, A. / Berndt, N. / Qi, J. / Georg, G.I. / Schonbrunn, E.
History
DepositionMay 7, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 11, 2022Provider: repository / Type: Initial release
Revision 1.1Aug 3, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Aug 24, 2022Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.3Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Bromodomain-containing protein 4
B: Bromodomain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,7606
Polymers30,1992
Non-polymers1,5614
Water4,107228
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)30.281, 39.895, 57.456
Angle α, β, γ (deg.)100.030, 104.500, 90.180
Int Tables number1
Space group name H-MP1

-
Components

#1: Protein Bromodomain-containing protein 4 / Protein HUNK1


Mass: 15099.380 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Plasmid: pNIC-Bsa4 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: O60885
#2: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6O2
#3: Chemical ChemComp-ZN1 / 4-[(4-{4-chloro-3-[(2-methylpropane-2-sulfonyl)amino]anilino}-5-methylpyrimidin-2-yl)amino]-2-fluoro-N-[1-(14-{3-[(2-{3-fluoro-4-[(piperidin-4-yl)carbamoyl]anilino}-5-methylpyrimidin-4-yl)amino]-5-[(2-methylpropane-2-sulfonyl)amino]phenyl}-14-oxo-4,7,10-trioxa-13-azatetradecanan-1-oyl)piperidin-4-yl]benzamide


Mass: 1375.010 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C64H82ClF2N15O11S2 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 228 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.19 Å3/Da / Density % sol: 43.8 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop
Details: 0.2 M Ammonium sulfate,0.1 M HEPES pH 7.5, 25% w/v Polyethylene glycol 3,350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-D / Wavelength: 1.0332 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Aug 9, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0332 Å / Relative weight: 1
ReflectionResolution: 1.15→54.71 Å / Num. obs: 55324 / % possible obs: 61.1 % / Redundancy: 1.7 % / CC1/2: 0.998 / Rmerge(I) obs: 0.038 / Rpim(I) all: 0.038 / Rrim(I) all: 0.054 / Net I/σ(I): 4.6 / Num. measured all: 96130
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
1.15-1.211.40.905138210200.4160.9051.280.57.7
3.64-54.711.80.023457325640.9970.0230.03310.289.7

-
Processing

Software
NameVersionClassification
Aimless0.7.4data scaling
PHENIX1.18.2-3874_3874refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3MXF

3mxf


Resolution: 1.4→39.24 Å / SU ML: 0.14 / Cross valid method: THROUGHOUT / σ(F): 1.97 / Phase error: 20.58 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1938 2106 4.62 %
Rwork0.1765 43485 -
obs0.1773 45591 90.37 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 55.63 Å2 / Biso mean: 20.1716 Å2 / Biso min: 9.22 Å2
Refinement stepCycle: final / Resolution: 1.4→39.24 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2098 0 107 228 2433
Biso mean--26.57 25.51 -
Num. residues----251
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 15

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
1.4-1.430.26411460.26582903304990
1.43-1.470.24681300.2262910304092
1.47-1.510.23921310.21132963309491
1.51-1.550.25061410.20862931307292
1.55-1.60.20171230.18952998312192
1.6-1.660.2011370.18232982311993
1.66-1.730.2311400.18112972311292
1.73-1.80.20531730.17982915308892
1.8-1.90.22431580.1792933309192
1.9-2.020.1911210.17492910303191
2.02-2.170.16721400.1682857299789
2.17-2.390.1851260.17442821294788
2.39-2.740.18771460.18342797294387
2.74-3.450.20811510.18092727287886
3.45-39.240.1621430.15192866300989
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
14.12871.00990.31216.8129-1.88085.6211-0.162-0.0823-0.5353-0.2941-0.034-0.1180.77670.14070.25470.23190.03060.00720.1214-0.01280.1971-3.9384-9.3905-18.2839
21.5616-0.4269-0.79071.1443-0.84652.5068-0.1349-0.09420.0363-0.1162-0.2321-0.24260.00770.50010.17090.15610.00850.02590.16930.05740.15124.72379.5872-17.6508
30.9722-0.239-0.21871.18890.37631.9199-0.0141-0.094-0.08860.0971-0.08440.02730.23480.03730.12070.10380.00130.00350.11010.00670.1192-5.1525-1.6495-12.8415
42.44911.3178-0.0862.1750.44462.03990.0202-0.06350.18820.0355-0.09540.1189-0.1143-0.12650.04670.09530.0283-0.01350.1076-0.00330.12-9.83459.1144-11.4864
53.76480.09480.10746.21271.78653.27460.0374-0.0231-0.39730.3311-0.13630.1810.3783-0.31350.16570.1734-0.0548-0.00410.13960.04390.1725-17.34012.050422.7775
61.89930.2942-1.60432.7241.65874.04780.0959-0.03430.09450.092-0.33280.26250.0787-0.5040.15740.1677-0.04130.00970.2023-0.0530.207-25.773520.409924.9744
72.4981-1.4573-1.80214.65694.83515.9401-0.0060.14220.0097-0.0123-0.15920.404-0.4845-0.4465-0.04250.14030.0135-0.01840.1411-0.0140.1743-21.589618.70499.9012
82.0391-0.1440.17892.1987-1.1093.0482-0.00310.0557-0.2737-0.107-0.04820.02260.26960.10730.03660.1111-0.00320.01070.1123-0.00610.1514-9.96654.975212.0088
91.5475-0.4308-1.03431.030.51721.60130.0112-0.00020.10150.0479-0.01510.0582-0.064-0.03930.03560.1139-0.0152-0.00670.10920.00570.1212-13.647614.424519.0776
103.0844-2.8962-2.55362.68282.47663.92680.1378-0.04880.314-0.16370.0222-0.2048-0.3380.1133-0.19070.1588-0.0349-0.00560.10270.00320.1762-12.155323.483412.0039
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 42 through 51 )A42 - 51
2X-RAY DIFFRACTION2chain 'A' and (resid 52 through 76 )A52 - 76
3X-RAY DIFFRACTION3chain 'A' and (resid 77 through 121 )A77 - 121
4X-RAY DIFFRACTION4chain 'A' and (resid 122 through 167 )A122 - 167
5X-RAY DIFFRACTION5chain 'B' and (resid 43 through 52 )B43 - 52
6X-RAY DIFFRACTION6chain 'B' and (resid 53 through 68 )B53 - 68
7X-RAY DIFFRACTION7chain 'B' and (resid 69 through 76 )B69 - 76
8X-RAY DIFFRACTION8chain 'B' and (resid 77 through 106 )B77 - 106
9X-RAY DIFFRACTION9chain 'B' and (resid 107 through 144 )B107 - 144
10X-RAY DIFFRACTION10chain 'B' and (resid 145 through 167 )B145 - 167

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more