[English] 日本語
Yorodumi
- PDB-5nnd: Crystal Structure of the first bromodomain of human BRD4 in compl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5nnd
TitleCrystal Structure of the first bromodomain of human BRD4 in complex with a diacetylated histone 4 peptide (H3K9ac/K14ac)
Components
  • Bromodomain-containing protein 4BRD4
  • Histone H3
KeywordsTRANSCRIPTION / Bromodomain / complex
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 / Chromatin modifying enzymes / epigenetic regulation of gene expression / positive regulation of G2/M transition of mitotic cell cycle / telomere organization / histone reader activity ...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 / Chromatin modifying enzymes / epigenetic regulation of gene expression / positive regulation of G2/M transition of mitotic cell cycle / telomere organization / histone reader activity / RNA Polymerase I Promoter Opening / Interleukin-7 signaling / Assembly of the ORC complex at the origin of replication / RNA polymerase II CTD heptapeptide repeat kinase activity / DNA methylation / Condensation of Prophase Chromosomes / HCMV Late Events / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / SIRT1 negatively regulates rRNA expression / PRC2 methylates histones and DNA / condensed nuclear chromosome / Defective pyroptosis / HDACs deacetylate histones / positive regulation of transcription elongation by RNA polymerase II / RNA Polymerase I Promoter Escape / transcription coregulator activity / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / lysine-acetylated histone binding / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / NoRC negatively regulates rRNA expression / B-WICH complex positively regulates rRNA expression / HDMs demethylate histones / PKMTs methylate histone lysines / RMTs methylate histone arginines / Meiotic recombination / Pre-NOTCH Transcription and Translation / nucleosome assembly / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / nucleosome / p53 binding / gene expression / chromosome / RUNX1 regulates transcription of genes involved in differentiation of HSCs / chromatin organization / Factors involved in megakaryocyte development and platelet production / HATs acetylate histones / regulation of inflammatory response / Senescence-Associated Secretory Phenotype (SASP) / positive regulation of canonical NF-kappaB signal transduction / Oxidative Stress Induced Senescence / Estrogen-dependent gene expression / Potential therapeutics for SARS / transcription coactivator activity / transcription cis-regulatory region binding / chromatin remodeling / cadherin binding / Amyloid fiber formation / protein heterodimerization activity / 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 / protein-containing complex / DNA binding / extracellular exosome / extracellular region / nucleoplasm / membrane / nucleus
Similarity search - Function
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 / Histone H3 signature 1. / Histone H3 signature 2. ...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 / Histone H3 signature 1. / Histone H3 signature 2. / Histone H3 / Histone H3/CENP-A / Bromodomain-like / Histone Acetyltransferase; Chain A / Histone H2A/H2B/H3 / Core histone H2A/H2B/H3/H4 / Histone-fold / 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 / Histone H3.1 / Histone H3-7
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.82 Å
AuthorsFilippakopoulos, P. / Picaud, S. / Pike, A.C.W. / 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: Lambert, J.P. / Picaud, S. / Fujisawa, T. / Hou, H. / Savitsky, P. / Uuskula-Reimand, L. / Gupta, G.D. / Abdouni, H. / Lin, Z.Y. / Tucholska, M. / Knight, J.D.R. / Gonzalez-Badillo, B. / St- ...Authors: Lambert, J.P. / Picaud, S. / Fujisawa, T. / Hou, H. / Savitsky, P. / Uuskula-Reimand, L. / Gupta, G.D. / Abdouni, H. / Lin, Z.Y. / Tucholska, M. / Knight, J.D.R. / Gonzalez-Badillo, B. / St-Denis, N. / Newman, J.A. / Stucki, M. / Pelletier, L. / Bandeira, N. / Wilson, M.D. / Filippakopoulos, P. / Gingras, A.C.
History
DepositionApr 8, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0May 16, 2018Provider: repository / Type: Initial release
Revision 1.1Nov 28, 2018Group: Data collection / Database references / Category: citation / Item: _citation.title
Revision 1.2Dec 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 1.3Feb 20, 2019Group: Data collection / Database references
Category: citation / database_PDB_rev ...citation / database_PDB_rev / database_PDB_rev_record / pdbx_database_proc
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year
Revision 1.4Jan 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
B: Bromodomain-containing protein 4
D: Histone H3
E: Histone H3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)34,4075
Polymers34,3454
Non-polymers621
Water2,270126
1
A: Bromodomain-containing protein 4
D: Histone H3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)17,2353
Polymers17,1732
Non-polymers621
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1160 Å2
ΔGint-5 kcal/mol
Surface area7690 Å2
MethodPISA
2
B: Bromodomain-containing protein 4
E: Histone H3


Theoretical massNumber of molelcules
Total (without water)17,1732
Polymers17,1732
Non-polymers00
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area940 Å2
ΔGint-8 kcal/mol
Surface area7800 Å2
MethodPISA
Unit cell
Length a, b, c (Å)42.630, 50.490, 64.540
Angle α, β, γ (deg.)90.00, 89.99, 90.00
Int Tables number4
Space group name H-MP1211

-
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 Histone H3 /


Mass: 2073.250 Da / Num. of mol.: 2 / Fragment: UNP residues 5-21 / Source method: obtained synthetically
Details: Histone H3 peptide acetylated at K9/K14 and phosphorylated at S10. C-terminal TYR added for UV detection
Source: (synth.) Homo sapiens (human) / References: UniProt: Q5TEC6, UniProt: P68431*PLUS
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL / Ethylene glycol


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 126 / 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: 2.02 Å3/Da / Density % sol: 39.18 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: 0.20M Na(acetate) 0.1M BTProp pH 7.5 20.0% PEG 3350 10.0% EtGly

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.9686 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 3, 2012
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9686 Å / Relative weight: 1
ReflectionResolution: 1.61→19.82 Å / Num. obs: 18357 / % possible obs: 99.2 % / Redundancy: 4.9 % / Rmerge(I) obs: 0.081 / Rpim(I) all: 0.041 / Rrim(I) all: 0.041 / Rsym value: 0.081 / Net I/σ(I): 9.9
Reflection shellResolution: 2.2→2.32 Å / Redundancy: 3 % / Rmerge(I) obs: 0.635 / Mean I/σ(I) obs: 2.2 / Num. unique all: 1952 / Rsym value: 0.635 / % possible all: 98.2

-
Processing

Software
NameVersionClassification
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing
REFMAC5.8.0155refinement
Cootmodel building
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2OSS

2oss


Resolution: 1.82→19.82 Å / Cor.coef. Fo:Fc: 0.928 / Cor.coef. Fo:Fc free: 0.86 / SU B: 7.541 / SU ML: 0.121 / Cross valid method: THROUGHOUT / ESU R: 0.17 / ESU R Free: 0.177 / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.28495 1173 5.1 %RANDOM
Rwork0.20604 ---
obs0.21015 18357 92.92 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso mean: 24.332 Å2
Baniso -1Baniso -2Baniso -3
1--0.78 Å20 Å20.08 Å2
2--1.03 Å20 Å2
3----0.25 Å2
Refinement stepCycle: 1 / Resolution: 1.82→19.82 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2188 0 4 126 2318
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0260.022284
X-RAY DIFFRACTIONr_bond_other_d0.0020.022194
X-RAY DIFFRACTIONr_angle_refined_deg2.3071.9933109
X-RAY DIFFRACTIONr_angle_other_deg1.2235076
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.8825272
X-RAY DIFFRACTIONr_dihedral_angle_2_deg38.74825.686102
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.90415389
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.038156
X-RAY DIFFRACTIONr_chiral_restr0.150.2331
X-RAY DIFFRACTIONr_gen_planes_refined0.0160.0212543
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02503
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it5.7083.5111074
X-RAY DIFFRACTIONr_mcbond_other5.6963.5061073
X-RAY DIFFRACTIONr_mcangle_it6.1316.461338
X-RAY DIFFRACTIONr_mcangle_other6.1366.4671339
X-RAY DIFFRACTIONr_scbond_it8.2624.2791210
X-RAY DIFFRACTIONr_scbond_other8.2594.281211
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other9.5487.5541767
X-RAY DIFFRACTIONr_long_range_B_refined9.06523.342588
X-RAY DIFFRACTIONr_long_range_B_other9.07223.2412569
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.82→1.867 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.312 75 -
Rwork0.247 1397 -
obs--81.01 %
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)
10.40540.00830.1090.19870.03320.5542-0.0397-0.00290.00790.02480.03120.0035-0.03810.00230.00840.051-0.0056-0.00860.0219-0.00720.037327.52412.756158.8006
20.39790.0386-0.40270.27630.14860.7241-0.0184-0-0.02040.05350.0187-0.01640.05070.0071-0.00030.056-0.0048-0.01550.02160.00920.038536.141422.116730.3562
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A42 - 165
2X-RAY DIFFRACTION2B42 - 165

+
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