[English] 日本語
Yorodumi
- PDB-6cj1: Crystal Structure of the first bromodomain of human BRD4 in compl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6cj1
TitleCrystal Structure of the first bromodomain of human BRD4 in complex with the inhibitor JWG071
ComponentsBromodomain-containing protein 4
KeywordsTRANSCRIPTION/INHIBITOR / Kinase / Inhibitor / BRD4 / TRANSCRIPTION / TRANSCRIPTION-INHIBITOR complex
Function / homology
Function and homology information


RNA polymerase II C-terminal domain binding / P-TEFb complex binding / negative regulation of DNA damage checkpoint / histone H4 reader activity / host-mediated suppression of viral transcription / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of T-helper 17 cell lineage commitment / : / RNA polymerase II CTD heptapeptide repeat kinase activity / condensed nuclear chromosome ...RNA polymerase II C-terminal domain binding / P-TEFb complex binding / negative regulation of DNA damage checkpoint / histone H4 reader activity / host-mediated suppression of viral transcription / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of T-helper 17 cell lineage commitment / : / RNA polymerase II CTD heptapeptide repeat kinase activity / condensed nuclear chromosome / transcription coregulator activity / positive regulation of transcription elongation by RNA polymerase II / p53 binding / chromosome / regulation of inflammatory response / histone binding / Potential therapeutics for SARS / transcription coactivator activity / positive regulation of canonical NF-kappaB signal transduction / 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-like ...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-like / Histone Acetyltransferase; Chain A / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-F2S / Chem-FND / NITRATE ION / Bromodomain-containing protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.53 Å
AuthorsXu, X. / Blacklow, S.C.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)P50 GM107618 United States
Leukemia & Lymphoma SocietySCOR 7003-13 United States
CitationJournal: ACS Chem. Biol. / Year: 2018
Title: Structural and Atropisomeric Factors Governing the Selectivity of Pyrimido-benzodiazipinones as Inhibitors of Kinases and Bromodomains.
Authors: Wang, J. / Erazo, T. / Ferguson, F.M. / Buckley, D.L. / Gomez, N. / Munoz-Guardiola, P. / Dieguez-Martinez, N. / Deng, X. / Hao, M. / Massefski, W. / Fedorov, O. / Offei-Addo, N.K. / Park, P. ...Authors: Wang, J. / Erazo, T. / Ferguson, F.M. / Buckley, D.L. / Gomez, N. / Munoz-Guardiola, P. / Dieguez-Martinez, N. / Deng, X. / Hao, M. / Massefski, W. / Fedorov, O. / Offei-Addo, N.K. / Park, P.M. / Dai, L. / DiBona, A. / Becht, K. / Kim, N.D. / McKeown, M.R. / Roberts, J.M. / Zhang, J. / Sim, T. / Alessi, D.R. / Bradner, J.E. / Lizcano, J.M. / Blacklow, S.C. / Qi, J. / Xu, X. / Gray, N.S.
History
DepositionFeb 25, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 29, 2018Provider: repository / Type: Initial release
Revision 1.1Oct 3, 2018Group: Data collection / Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title
Revision 1.2Feb 20, 2019Group: Author supporting evidence / Data collection / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Jan 1, 2020Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.4Oct 4, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
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)16,3778
Polymers14,8411
Non-polymers1,5367
Water4,504250
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)40.050, 42.227, 84.900
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 1 molecules A

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


Mass: 14841.152 Da / Num. of mol.: 1 / Fragment: residues 44-166
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Production host: Escherichia coli (E. coli) / References: UniProt: O60885

-
Non-polymers , 5 types, 257 molecules

#2: Chemical ChemComp-F2S / 11-[(2R)-butan-2-yl]-2-({2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]phenyl}amino)-5-methyl-5,11-dihydro-6H-pyrimido[4,5-b][1,4]benzodiazepin-6-one


Mass: 612.765 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C34H44N8O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-FND / 11-[(2S)-butan-2-yl]-2-({2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]phenyl}amino)-5-methyl-5,11-dihydro-6H-pyrimido[4,5-b][1,4]benzodiazepin-6-one


Mass: 612.765 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C34H44N8O3
#4: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6O2
#5: Chemical ChemComp-NO3 / NITRATE ION


Mass: 62.005 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: NO3
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 250 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.42 Å3/Da / Density % sol: 49.15 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop
Details: 100mM Sodium Nitrate, 5% Ethylene Glycol, 18% (w/v) PEG3350

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.9792 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Aug 19, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9792 Å / Relative weight: 1
ReflectionResolution: 1.53→84.9 Å / Num. obs: 22183 / % possible obs: 99 % / Redundancy: 6.8 % / CC1/2: 0.982 / Rmerge(I) obs: 0.2 / Rpim(I) all: 0.092 / Rrim(I) all: 0.239 / Net I/σ(I): 15
Reflection shellResolution: 1.53→1.56 Å / Redundancy: 6.9 % / Mean I/σ(I) obs: 2.1 / Num. unique obs: 1059 / CC1/2: 0.499 / Rpim(I) all: 0.577 / % possible all: 97.9

-
Processing

Software
NameVersionClassification
PHENIX(1.10_2155)refinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4WIV

4wiv


Resolution: 1.53→42.45 Å / SU ML: 0.19 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 19.86
RfactorNum. reflection% reflection
Rfree0.192 1132 5.12 %
Rwork0.1738 --
obs0.1748 22129 98.72 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 1.53→42.45 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1043 0 65 252 1360
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0111188
X-RAY DIFFRACTIONf_angle_d1.3491616
X-RAY DIFFRACTIONf_dihedral_angle_d13.234714
X-RAY DIFFRACTIONf_chiral_restr0.065164
X-RAY DIFFRACTIONf_plane_restr0.008206
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.53-1.59970.32651260.3192562X-RAY DIFFRACTION98
1.5997-1.6840.26951390.2322530X-RAY DIFFRACTION97
1.684-1.78950.24291480.21122537X-RAY DIFFRACTION98
1.7895-1.92770.22111370.17072605X-RAY DIFFRACTION98
1.9277-2.12170.16861390.14452623X-RAY DIFFRACTION99
2.1217-2.42870.17091450.15272647X-RAY DIFFRACTION100
2.4287-3.05970.16861500.16642684X-RAY DIFFRACTION100
3.0597-42.46630.17761480.16692809X-RAY DIFFRACTION100

+
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