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

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6fsy
TitleCrystal Structure of the first bromodomain of human BRD4 in complex with a 3,5-dimethylisoxazol ligand
ComponentsBromodomain-containing protein 4
KeywordsTRANSCRIPTION / Bromodomain / ligand / isoxazole / Structural Genomics / Structural Genomics Consortium / SGC
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-E5Q / Bromodomain-containing protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.34 Å
AuthorsFilippakopoulos, P. / Picaud, S. / Conway, S.J. / Pike, A.C.W. / Krojer, T. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. / Structural Genomics Consortium (SGC)
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
Wellcome Trust095751/Z/11/Z United Kingdom
CitationJournal: Bioorg.Med.Chem. / Year: 2018
Title: BET bromodomain ligands: Probing the WPF shelf to improve BRD4 bromodomain affinity and metabolic stability.
Authors: Jennings, L.E. / Schiedel, M. / Hewings, D.S. / Picaud, S. / Laurin, C.M.C. / Bruno, P.A. / Bluck, J.P. / Scorah, A.R. / See, L. / Reynolds, J.K. / Moroglu, M. / Mistry, I.N. / Hicks, A. / ...Authors: Jennings, L.E. / Schiedel, M. / Hewings, D.S. / Picaud, S. / Laurin, C.M.C. / Bruno, P.A. / Bluck, J.P. / Scorah, A.R. / See, L. / Reynolds, J.K. / Moroglu, M. / Mistry, I.N. / Hicks, A. / Guzanov, P. / Clayton, J. / Evans, C.N.G. / Stazi, G. / Biggin, P.C. / Mapp, A.K. / Hammond, E.M. / Humphreys, P.G. / Filippakopoulos, P. / Conway, S.J.
History
DepositionFeb 20, 2018Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 18, 2018Provider: repository / Type: Initial release
Revision 1.1Apr 24, 2019Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp / citation ...chem_comp / citation / citation_author / entity / pdbx_database_proc / pdbx_entity_nonpoly
Item: _chem_comp.name / _citation.country ..._chem_comp.name / _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 / _entity.pdbx_description / _pdbx_entity_nonpoly.name
Revision 1.2Jan 17, 2024Group: 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)15,5204
Polymers15,0991
Non-polymers4203
Water2,810156
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area400 Å2
ΔGint6 kcal/mol
Surface area7540 Å2
MethodPISA
Unit cell
Length a, b, c (Å)38.316, 42.910, 79.797
Angle α, β, γ (deg.)90.000, 90.000, 90.000
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
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): R3 / References: UniProt: O60885
#2: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6O2
#3: Chemical ChemComp-E5Q / 3-(3,5-dimethyl-1,2-oxazol-4-yl)-5-[(~{R})-oxidanyl(pyridin-3-yl)methyl]phenol


Mass: 296.321 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C17H16N2O3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 156 / 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: 2.17 Å3/Da / Density % sol: 43.38 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 5.5 / Details: 20 % PEG 3350 and 0.1 M citrate pH 5.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.96861 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Dec 18, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.96861 Å / Relative weight: 1
ReflectionResolution: 1.338→29.22 Å / Num. obs: 30364 / % possible obs: 99.7 % / Redundancy: 6.2 % / Rmerge(I) obs: 0.078 / Rpim(I) all: 0.034 / Rrim(I) all: 0.085 / Rsym value: 0.078 / Net I/av σ(I): 4.4 / Net I/σ(I): 11.3
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsRpim(I) allRrim(I) allRsym value% possible all
1.34-1.415.40.5631.342640.2630.6230.56398.1
1.41-1.55.80.37241440.1650.4060.3799.9
1.5-1.66.30.2562.839300.1080.2780.25699.9
1.6-1.736.50.178436260.0750.1940.178100
1.73-1.896.40.1295.233690.0550.1410.129100
1.89-2.126.50.0926.930520.0390.10.09299.9
2.12-2.446.50.0757.927220.0320.0820.075100
2.44-2.996.50.0688.223340.0290.0740.068100
2.99-4.236.30.0598.818390.0260.0650.059100
4.23-29.225.70.0588.910840.0260.0640.05899.7

-
Phasing

PhasingMethod: molecular replacement
Phasing MRModel details: Phaser MODE: MR_AUTO
Highest resolutionLowest resolution
Rotation2.5 Å28.58 Å
Translation2.5 Å28.58 Å

-
Processing

Software
NameVersionClassification
SCALA3.3.22data scaling
PHASER2.5.7phasing
REFMACrefinement
PDB_EXTRACT3.24data extraction
XDSdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: Ensemble of 2OSS, 2OUO, 2GRC, 2OO1, 3DAI, 3D7C, 3DWY

2oss

2ouo

2grc

2oo1

3dai

3d7c

3dwy


Resolution: 1.34→29.22 Å / Cor.coef. Fo:Fc: 0.974 / Cor.coef. Fo:Fc free: 0.964 / SU B: 2.271 / SU ML: 0.042 / SU R Cruickshank DPI: 0.0565 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.056 / ESU R Free: 0.057
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.1997 1430 4.7 %RANDOM
Rwork0.1555 ---
obs0.1575 28822 99.84 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 66.62 Å2 / Biso mean: 19.083 Å2 / Biso min: 9.39 Å2
Baniso -1Baniso -2Baniso -3
1-0.65 Å20 Å2-0 Å2
2---0.38 Å20 Å2
3----0.27 Å2
Refinement stepCycle: final / Resolution: 1.34→29.22 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1049 0 30 156 1235
Biso mean--19.47 29.56 -
Num. residues----127
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.021127
X-RAY DIFFRACTIONr_bond_other_d0.0070.021029
X-RAY DIFFRACTIONr_angle_refined_deg1.7151.9911535
X-RAY DIFFRACTIONr_angle_other_deg1.0422.9862408
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.9415131
X-RAY DIFFRACTIONr_dihedral_angle_2_deg40.27825.38552
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.49715194
X-RAY DIFFRACTIONr_dihedral_angle_4_deg26.213154
X-RAY DIFFRACTIONr_chiral_restr0.1040.2160
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.0211218
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02213
X-RAY DIFFRACTIONr_rigid_bond_restr2.41132156
X-RAY DIFFRACTIONr_sphericity_free20.174594
X-RAY DIFFRACTIONr_sphericity_bonded9.18652185
LS refinement shellResolution: 1.34→1.375 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.325 87 -
Rwork0.269 2091 -
all-2178 -
obs--99.32 %

+
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