[English] 日本語
Yorodumi
- PDB-8qar: Crystal Structure of the first bromodomain of BRD4 in complex wit... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8qar
TitleCrystal Structure of the first bromodomain of BRD4 in complex with acetyl-pyrrole derivative compound 98
ComponentsBromodomain-containing protein 4
KeywordsTRANSCRIPTION / four helical bundle
Function / homology
Function and homology information


RNA polymerase II C-terminal domain binding / P-TEFb complex binding / negative regulation of DNA damage checkpoint / 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 / condensed nuclear chromosome / histone reader activity / : ...RNA polymerase II C-terminal domain binding / P-TEFb complex binding / negative regulation of DNA damage checkpoint / 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 / condensed nuclear chromosome / histone reader activity / : / positive regulation of transcription elongation by RNA polymerase II / transcription coregulator activity / p53 binding / chromosome / regulation of inflammatory response / histone binding / Potential therapeutics for SARS / positive regulation of canonical NF-kappaB signal transduction / transcription coactivator activity / transcription cis-regulatory region binding / chromatin remodeling / protein serine/threonine kinase activity / DNA damage response / chromatin binding / regulation of transcription by RNA polymerase II / chromatin / 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 I / Brdt, bromodomain, repeat II / 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 I / Brdt, bromodomain, repeat II / 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-GI0 / Bromodomain-containing protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.5 Å
AuthorsDalle Vedove, A. / Cazzanelli, G. / Lolli, G.
Funding support Italy, 1items
OrganizationGrant numberCountry
Italian Association for Cancer ResearchMFAG 2017 - ID. 19882 Italy
CitationJournal: Protein Sci. / Year: 2024
Title: Enhanced cellular death in liver and breast cancer cells by dual BET/BRPF1 inhibitors.
Authors: Cazzanelli, G. / Dalle Vedove, A. / Sbardellati, N. / Valer, L. / Caflisch, A. / Lolli, G.
History
DepositionAug 23, 2023Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 11, 2024Provider: repository / Type: Initial release
Revision 1.1Mar 26, 2025Group: Database references / Structure summary / Category: citation / citation_author / pdbx_entry_details
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Bromodomain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)15,6344
Polymers15,0991
Non-polymers5353
Water2,342130
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area360 Å2
ΔGint5 kcal/mol
Surface area7520 Å2
MethodPISA
Unit cell
Length a, b, c (Å)37.320, 44.380, 78.415
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

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


Mass: 15099.380 Da / Num. of mol.: 1 / Mutation: First bromodomain (residues 1796-1899)
Source method: isolated from a genetically manipulated source
Details: First two residues SM derive from the expression tag
Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1
Production host: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (bacteria)
References: UniProt: O60885
#2: Chemical ChemComp-GI0 / 3-methyl-1-[2-[4-[(4-methyl-1~{H}-pyrazol-3-yl)methyl]piperazin-1-yl]-1,3-thiazol-4-yl]-2,5,6,7-tetrahydroisoindol-4-one


Mass: 410.536 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C21H26N6OS / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 130 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.15 Å3/Da / Density % sol: 42.8 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5 / Details: 16% PEG 3350, 20% ethylene glycol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: ELETTRA / Beamline: 11.2C / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 28, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.5→78.42 Å / Num. obs: 21574 / % possible obs: 100 % / Redundancy: 12.3 % / CC1/2: 0.994 / Rmerge(I) obs: 0.15 / Rpim(I) all: 0.045 / Rrim(I) all: 0.156 / Χ2: 0.98 / Net I/σ(I): 9.6 / Num. measured all: 265637
Reflection shellResolution: 1.5→1.53 Å / % possible obs: 100 % / Redundancy: 11.7 % / Rmerge(I) obs: 1.187 / Num. measured all: 12284 / Num. unique obs: 1052 / CC1/2: 0.77 / Rpim(I) all: 0.36 / Rrim(I) all: 1.242 / Χ2: 0.98 / Net I/σ(I) obs: 2.2

-
Processing

Software
NameVersionClassification
PHENIX(1.11.1_2575: ???)refinement
Aimlessdata scaling
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.5→39.208 Å / SU ML: 0.12 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 19.34 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2008 1075 5 %
Rwork0.166 --
obs0.1676 21515 99.97 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.5→39.208 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1052 0 37 130 1219
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0091121
X-RAY DIFFRACTIONf_angle_d1.0531524
X-RAY DIFFRACTIONf_dihedral_angle_d14.64684
X-RAY DIFFRACTIONf_chiral_restr0.05157
X-RAY DIFFRACTIONf_plane_restr0.007195
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.5-1.56830.24791360.2252491X-RAY DIFFRACTION100
1.5683-1.6510.24391430.20222501X-RAY DIFFRACTION100
1.651-1.75440.23361180.18472528X-RAY DIFFRACTION100
1.7544-1.88990.21941370.1762524X-RAY DIFFRACTION100
1.8899-2.08010.21181340.16222540X-RAY DIFFRACTION100
2.0801-2.3810.19821390.14962547X-RAY DIFFRACTION100
2.381-2.99970.18941360.16212588X-RAY DIFFRACTION100
2.9997-39.2080.18741320.1622721X-RAY DIFFRACTION100
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)
11.9469-0.0168-0.10056.08563.55053.72350.19440.03110.077-0.1736-0.0287-0.245-0.3366-0.1428-0.16810.2177-0.00370.01940.16350.03970.178114.02819.2375-15.2116
20.75760.0162-0.20592.1784-1.1672.7493-0.01320.041-0.1123-0.3947-0.04430.0790.3997-0.2018-0.05470.2529-0.01930.00320.2059-0.00530.20879.8819-11.4291-20.9517
30.89130.9663-0.37972.4805-0.24521.5072-0.0257-0.0870.11740.18430.07940.2836-0.079-0.0371-0.0460.15190.0250.04060.1740.01280.192810.43063.0802-4.5347
41.61440.2069-0.98671.76160.73773.35020.01760.17890.0027-0.11410.04020.22130.0352-0.4175-0.0920.1495-0.0208-0.00930.2050.02240.16489.5875-5.3542-17.9846
50.72710.89560.70442.19311.4112.7443-0.0548-0.011-0.06080.15240.1730.0290.1230.1361-0.12640.16260.02210.00360.17570.01120.146417.1657-4.6404-6.6961
66.46750.961-0.92294.7104-4.52344.34490.0709-1.30960.24380.87030.18680.08940.28920.957-0.37410.37960.1005-0.00610.4344-0.01250.204317.39962.45728.195
71.55270.7119-0.13434.1871.97543.6468-0.0516-0.0397-0.1170.38540.13660.08890.50750.1248-0.05040.23730.03530.02840.15990.02750.165410.9892-12.1573-2.1373
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 42 through 51 )
2X-RAY DIFFRACTION2chain 'A' and (resid 52 through 68 )
3X-RAY DIFFRACTION3chain 'A' and (resid 69 through 106 )
4X-RAY DIFFRACTION4chain 'A' and (resid 107 through 121 )
5X-RAY DIFFRACTION5chain 'A' and (resid 122 through 139 )
6X-RAY DIFFRACTION6chain 'A' and (resid 140 through 144 )
7X-RAY DIFFRACTION7chain 'A' and (resid 145 through 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