[English] 日本語
Yorodumi
- PDB-6g0s: Crystal Structure of the first bromodomain of human BRD4 in compl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6g0s
TitleCrystal Structure of the first bromodomain of human BRD4 in complex with an acetylated SIRT7 peptide (K272ac/K275ac)
Components
  • Bromodomain-containing protein 4BRD4
  • NAD-dependent protein deacetylase sirtuin-7
KeywordsTRANSCRIPTION / Bromodomain / complex
Function / homology
Function and homology information


: / regulation of transcription of nucleolar large rRNA by RNA polymerase I / : / nucleolus organizer region / : / : / : / protein depropionylation / protein-propionyllysine depropionylase activity / protein deglutarylation ...: / regulation of transcription of nucleolar large rRNA by RNA polymerase I / : / nucleolus organizer region / : / : / : / protein depropionylation / protein-propionyllysine depropionylase activity / protein deglutarylation / peptidyl-lysine desuccinylation / protein-glutaryllysine deglutarylase activity / NAD-dependent histone H3K18 deacetylase activity / regulation of double-strand break repair via nonhomologous end joining / protein-succinyllysine desuccinylase activity / R-loop processing / deacetylase activity / homologous chromosome pairing at meiosis / NAD-dependent protein lysine deacetylase activity / protein acetyllysine N-acetyltransferase / positive regulation of rRNA processing / protein deacetylation / regulation of protein export from nucleus / regulation of mitochondrion organization / histone deacetylase activity / regulation of gluconeogenesis / rRNA transcription / RNA polymerase II C-terminal domain binding / negative regulation of DNA damage checkpoint / P-TEFb complex binding / NAD+ binding / negative regulation by host of viral transcription / regulation of DNA repair / positive regulation of T-helper 17 cell lineage commitment / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / negative regulation of protein ubiquitination / positive regulation of G2/M transition of mitotic cell cycle / histone reader activity / RNA polymerase II CTD heptapeptide repeat kinase activity / condensed nuclear chromosome / positive regulation of transcription elongation by RNA polymerase II / transcription coregulator activity / lysine-acetylated histone binding / osteoblast differentiation / transcription corepressor activity / p53 binding / site of double-strand break / 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 repair / DNA damage response / chromatin binding / chromatin / nucleolus / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / enzyme binding / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / nucleoplasm / metal ion binding / nucleus / cytoplasm
Similarity search - Function
Sirtuin family / Sir2 family / Sirtuin family, catalytic core domain / Sirtuin catalytic domain profile. / DHS-like NAD/FAD-binding domain superfamily / Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / NET domain superfamily / NET domain profile. / Brdt, bromodomain, repeat II ...Sirtuin family / Sir2 family / Sirtuin family, catalytic core domain / Sirtuin catalytic domain profile. / DHS-like NAD/FAD-binding domain superfamily / Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / NET domain superfamily / NET domain profile. / Brdt, bromodomain, repeat II / Brdt, bromodomain, repeat I / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain-like / Histone Acetyltransferase; Chain A / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
Bromodomain-containing protein 4 / NAD-dependent protein deacetylase sirtuin-7
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.48 Å
AuthorsFilippakopoulos, P. / Picaud, S. / Krojer, T. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C.
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
Wellcome Trust095751/Z/11/Z United Kingdom
CitationJournal: Mol Cell / Year: 2019
Title: Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains.
Authors: Jean-Philippe Lambert / Sarah Picaud / Takao Fujisawa / Huayun Hou / Pavel Savitsky / Liis Uusküla-Reimand / Gagan D Gupta / Hala Abdouni / Zhen-Yuan Lin / Monika Tucholska / James D R ...Authors: Jean-Philippe Lambert / Sarah Picaud / Takao Fujisawa / Huayun Hou / Pavel Savitsky / Liis Uusküla-Reimand / Gagan D Gupta / Hala Abdouni / Zhen-Yuan Lin / Monika Tucholska / James D R Knight / Beatriz Gonzalez-Badillo / Nicole St-Denis / Joseph A Newman / Manuel Stucki / Laurence Pelletier / Nuno Bandeira / Michael D Wilson / Panagis Filippakopoulos / Anne-Claude Gingras /
Abstract: Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, ...Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, BRD3, BRD4, and BRDT following treatment with the pan-BET BRD inhibitor JQ1, revealing broad rewiring of the interaction landscape, with three distinct classes of behavior for the 603 unique interactors identified. A group of proteins associate in a JQ1-sensitive manner with BET BRDs through canonical and new binding modes, while two classes of extra-terminal (ET)-domain binding motifs mediate acetylation-independent interactions. Last, we identify an unexpected increase in several interactions following JQ1 treatment that define negative functions for BRD3 in the regulation of rRNA synthesis and potentially RNAPII-dependent gene expression that result in decreased cell proliferation. Together, our data highlight the contributions of BET protein modules to their interactomes allowing for a better understanding of pharmacological rewiring in response to JQ1.
History
DepositionMar 19, 2018Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 28, 2018Provider: repository / Type: Initial release
Revision 1.1Dec 26, 2018Group: Data collection / 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 1.2Feb 20, 2019Group: Data collection / Database references
Category: citation / database_PDB_rev ...citation / database_PDB_rev / database_PDB_rev_record / pdbx_database_proc / pdbx_struct_ref_seq_depositor_info
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year / _pdbx_struct_ref_seq_depositor_info.db_seq_one_letter_code
Revision 1.3Jan 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
D: NAD-dependent protein deacetylase sirtuin-7
B: Bromodomain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,7966
Polymers31,6093
Non-polymers1863
Water4,414245
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3210 Å2
ΔGint-13 kcal/mol
Surface area14340 Å2
MethodPISA
Unit cell
Length a, b, c (Å)42.393, 59.376, 106.017
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 / BRD4 / 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: pNIC28-Bsa4 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): R3 / References: UniProt: O60885
#2: Protein/peptide NAD-dependent protein deacetylase sirtuin-7 / Regulatory protein SIR2 homolog 7 / SIR2-like protein 7


Mass: 1410.677 Da / Num. of mol.: 1 / Source method: obtained synthetically
Details: SIRT7 peptide acetylated at K272 and K275 C-terminal TYR added for UV detection
Source: (synth.) Homo sapiens (human)
References: UniProt: Q9NRC8, Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 245 / 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: 2.12 Å3/Da / Density % sol: 41.88 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: 20.0 % PEG3350 10.0 % EtGly 0.1 M bis-tris-propane pH 8.5 0.2M NaOOCCH3

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.9763 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Apr 28, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9763 Å / Relative weight: 1
ReflectionResolution: 1.475→51.805 Å / Num. all: 45984 / Num. obs: 45984 / % possible obs: 100 % / Redundancy: 7.2 % / Rpim(I) all: 0.031 / Rrim(I) all: 0.084 / Rsym value: 0.077 / Net I/av σ(I): 7.4 / Net I/σ(I): 14.5 / Num. measured all: 328804
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsRpim(I) allRrim(I) allRsym value% possible all
1.48-1.5570.9550.866340.3851.0310.955100
1.55-1.657.20.6341.262530.2520.6830.634100
1.65-1.767.20.4431.759210.1770.4780.443100
1.76-1.97.20.2612.954760.1040.2820.261100
1.9-2.097.30.1465.150850.0580.1580.146100
2.09-2.337.30.0898.346200.0350.0960.089100
2.33-2.697.30.0661141140.0260.0710.066100
2.69-3.37.10.04614.735120.0190.050.046100
3.3-4.6670.03517.427480.0140.0380.035100
4.66-51.8056.50.03514.316210.0150.0380.03599.7

-
Phasing

PhasingMethod: molecular replacement
Phasing MRModel details: Phaser MODE: MR_AUTO
Highest resolutionLowest resolution
Rotation2 Å39.54 Å
Translation2 Å39.54 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: 1.48→51.8 Å / Cor.coef. Fo:Fc: 0.966 / Cor.coef. Fo:Fc free: 0.956 / SU B: 2.795 / SU ML: 0.052 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.071 / ESU R Free: 0.074
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2095 2061 4.5 %RANDOM
Rwork0.1771 ---
obs0.1786 43853 99.97 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 65.9 Å2 / Biso mean: 21.015 Å2 / Biso min: 9.82 Å2
Baniso -1Baniso -2Baniso -3
1-0.22 Å20 Å20 Å2
2--0.01 Å2-0 Å2
3----0.23 Å2
Refinement stepCycle: final / Resolution: 1.48→51.8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2162 0 12 245 2419
Biso mean--25.8 30.97 -
Num. residues----262
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.022270
X-RAY DIFFRACTIONr_bond_other_d0.0020.022151
X-RAY DIFFRACTIONr_angle_refined_deg1.6541.9763095
X-RAY DIFFRACTIONr_angle_other_deg1.02634970
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.7715267
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.90925.755106
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.17715383
X-RAY DIFFRACTIONr_dihedral_angle_4_deg22.081155
X-RAY DIFFRACTIONr_chiral_restr0.1090.2332
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.0212540
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02509
LS refinement shellResolution: 1.475→1.513 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.314 171 -
Rwork0.29 3206 -
all-3377 -
obs--99.97 %
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)
10.394-0.244-0.4160.37970.32140.5796-0.06040.00850.00630.00680.03750.00270.03850.01560.02290.0335-0.00350.00530.013-0.00270.06533.34262.142912.6876
20.1911-0.1186-0.42850.25780.15031.0535-0.03240.0155-0.0180.03360.0030.05420.0426-0.03990.02940.0334-0.00490.00690.00260.00320.078810.29972.428141.4257
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A42 - 168
2X-RAY DIFFRACTION2B43 - 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