[English] 日本語
Yorodumi
- PDB-3uvx: Crystal Structure of the first bromodomain of human BRD4 in compl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3uvx
TitleCrystal Structure of the first bromodomain of human BRD4 in complex with a diacetylated histone 4 peptide (H4K12acK16ac)
Components
  • Bromodomain-containing protein 4
  • diacetylated histone 4 peptide
KeywordsTRANSCRIPTION/PROTEIN BINDING / Bromodomain / Bromodomain containing protein 4 / CAP / HUNK1 / MCAP / Mitotic chromosome associated protein / peptide complex / Structural Genomics Consortium / SGC / TRANSCRIPTION-PROTEIN BINDING 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 / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / Replacement of protamines by nucleosomes in the male pronucleus ...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 / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / : / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / RNA polymerase II CTD heptapeptide repeat kinase activity / telomere organization / Inhibition of DNA recombination at telomere / RNA Polymerase I Promoter Opening / Meiotic synapsis / Assembly of the ORC complex at the origin of replication / SUMOylation of chromatin organization proteins / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / DNA methylation / Condensation of Prophase Chromosomes / Chromatin modifications during the maternal to zygotic transition (MZT) / SIRT1 negatively regulates rRNA expression / HCMV Late Events / condensed nuclear chromosome / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / Regulation of endogenous retroelements by KRAB-ZFP proteins / Defective pyroptosis / transcription coregulator activity / HDACs deacetylate histones / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / positive regulation of transcription elongation by RNA polymerase II / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / HDMs demethylate histones / G2/M DNA damage checkpoint / NoRC negatively regulates rRNA expression / DNA Damage/Telomere Stress Induced Senescence / B-WICH complex positively regulates rRNA expression / PKMTs methylate histone lysines / Meiotic recombination / Pre-NOTCH Transcription and Translation / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / Transcriptional regulation of granulopoiesis / HCMV Early Events / p53 binding / structural constituent of chromatin / nucleosome / nucleosome assembly / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromosome / HATs acetylate histones / RUNX1 regulates transcription of genes involved in differentiation of HSCs / chromatin organization / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / Processing of DNA double-strand break ends / regulation of inflammatory response / Senescence-Associated Secretory Phenotype (SASP) / histone binding / Oxidative Stress Induced Senescence / Estrogen-dependent gene expression / Potential therapeutics for SARS / transcription coactivator activity / chromosome, telomeric region / positive regulation of canonical NF-kappaB signal transduction / transcription cis-regulatory region binding / chromatin remodeling / Amyloid fiber formation / protein heterodimerization activity / 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 / protein-containing complex / DNA binding / RNA binding / extracellular exosome / extracellular region / nucleoplasm / nucleus / membrane
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 / TATA box binding protein associated factor ...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 / TATA box binding protein associated factor / TATA box binding protein associated factor (TAF), histone-like fold domain / Bromodomain-like / Histone H4, conserved site / Histone H4 signature. / Histone H4 / Histone H4 / CENP-T/Histone H4, histone fold / Centromere kinetochore component CENP-T histone fold / Histone Acetyltransferase; Chain A / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Histone-fold / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
FORMIC ACID / Bromodomain-containing protein 4 / Histone H4
Similarity search - Component
Biological speciesHomo sapiens (human)
homo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.91 Å
AuthorsFilippakopoulos, P. / Picaud, S. / Keates, T. / Ugochukwu, E. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Weigelt, J. / Bountra, C. / Knapp, S. / Structural Genomics Consortium (SGC)
CitationJournal: Cell(Cambridge,Mass.) / Year: 2012
Title: Histone recognition and large-scale structural analysis of the human bromodomain family.
Authors: Filippakopoulos, P. / Picaud, S. / Mangos, M. / Keates, T. / Lambert, J.P. / Barsyte-Lovejoy, D. / Felletar, I. / Volkmer, R. / Muller, S. / Pawson, T. / Gingras, A.C. / Arrowsmith, C.H. / Knapp, S.
History
DepositionNov 30, 2011Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 25, 2012Provider: repository / Type: Initial release
Revision 1.1Apr 11, 2012Group: Database references
Revision 1.2Jan 31, 2018Group: Source and taxonomy / Structure summary / Category: audit_author / pdbx_entity_src_syn
Item: _audit_author.name / _pdbx_entity_src_syn.ncbi_taxonomy_id / _pdbx_entity_src_syn.organism_scientific
Revision 1.3Sep 13, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_leaving_atom_flag / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.4Dec 6, 2023Group: Data collection / Category: chem_comp_atom / chem_comp_bond / Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2
Revision 1.5Oct 9, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Bromodomain-containing protein 4
B: diacetylated histone 4 peptide
hetero molecules


Theoretical massNumber of molelcules
Total (without water)16,6278
Polymers16,3812
Non-polymers2466
Water1,78399
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1950 Å2
ΔGint-19 kcal/mol
Surface area7520 Å2
MethodPISA
Unit cell
Length a, b, c (Å)43.940, 52.380, 57.620
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
DetailsMonomer

-
Components

-
Protein / Protein/peptide , 2 types, 2 molecules AB

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


Mass: 15099.380 Da / Num. of mol.: 1 / Fragment: unp residues 44-168
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)-R3 / References: UniProt: O60885
#2: Protein/peptide diacetylated histone 4 peptide / Peptide (H4K12acK16ac)


Mass: 1281.511 Da / Num. of mol.: 1 / Source method: obtained synthetically
Details: Human Histone 4 peptide (Uniprot: P62805) residues 11-21 acetylated on K12 and K16
Source: (synth.) homo sapiens (human) / References: UniProt: P62805*PLUS

-
Non-polymers , 4 types, 105 molecules

#3: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Na
#4: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#5: Chemical ChemComp-FMT / FORMIC ACID


Mass: 46.025 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: CH2O2
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 99 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.02 Å3/Da / Density meas: 39.23 Mg/m3 / Density % sol: 39.23 %
Crystal growTemperature: 278 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: 0.35M NaFortmate 20% PEG 3350 10% EtGly, pH 7.5, VAPOR DIFFUSION, SITTING DROP, temperature 278K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.52 Å
DetectorType: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: Dec 6, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.52 Å / Relative weight: 1
ReflectionRedundancy: 4.4 % / Av σ(I) over netI: 4.8 / Number: 47477 / Rsym value: 0.112 / D res high: 1.91 Å / D res low: 22.497 Å / Num. obs: 10804 / % possible obs: 99.9
Diffraction reflection shell
Highest resolution (Å)Lowest resolution (Å)% possible obs (%)IDRmerge(I) obsRsym valueRedundancy
6.0422.598.210.0720.0723.9
4.276.0410010.0720.0724.4
3.494.2710010.0720.0724.4
3.023.4910010.0860.0864.5
2.73.0210010.1080.1084.5
2.472.710010.1540.1544.5
2.282.4710010.2070.2074.5
2.142.2810010.2670.2674.5
2.012.1499.910.3980.3984.4
1.912.0110010.6170.6174.2
ReflectionResolution: 1.91→24.09 Å / Num. all: 10815 / Num. obs: 10804 / % possible obs: 99.9 % / Redundancy: 4.4 % / Biso Wilson estimate: 26.6 Å2 / Rmerge(I) obs: 0.112 / Rsym value: 0.112 / Net I/σ(I): 8.1
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allRsym value% possible all
1.91-2.014.20.6171.2640215380.617100
2.01-2.144.40.3981.9650814660.39899.9
2.14-2.284.50.2672.8614413800.267100
2.28-2.474.50.2073.6565412690.207100
2.47-2.74.50.1544.7540812070.154100
2.7-3.024.50.1086.5486710850.108100
3.02-3.494.50.0867.343459670.086100
3.49-4.274.40.0728.237378400.072100
4.27-6.044.40.0727.928766590.072100
6.04-22.4973.90.0727.115363930.07298.2

-
Phasing

PhasingMethod: molecular replacement
Phasing MRRfactor: 53.45 / Model details: Phaser MODE: MR_AUTO
Highest resolutionLowest resolution
Rotation2.5 Å22.5 Å
Translation2.5 Å22.5 Å

-
Processing

Software
NameVersionClassificationNB
SCALA3.3.16data scaling
PHASER2.1.4phasing
REFMACrefinement
PDB_EXTRACT3.1data extraction
CrystalCleardata collection
MOSFLMdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: Ensemble of 2OSS, 2OUO, 2GRC, 2OO1, 3DAI, 3D7C

2oss

2ouo

2grc

2oo1

3dai

3d7c


Resolution: 1.91→24.09 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.944 / WRfactor Rfree: 0.216 / WRfactor Rwork: 0.1627 / Occupancy max: 1 / Occupancy min: 0.5 / FOM work R set: 0.8728 / SU B: 6.294 / SU ML: 0.098 / SU R Cruickshank DPI: 0.1569 / SU Rfree: 0.1476 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.157 / ESU R Free: 0.148 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES: WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2187 517 4.8 %RANDOM
Rwork0.1672 ---
all0.1697 10780 --
obs0.1697 10766 99.87 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 120.77 Å2 / Biso mean: 27.8702 Å2 / Biso min: 11.66 Å2
Baniso -1Baniso -2Baniso -3
1--0.82 Å20 Å20 Å2
2--1.06 Å20 Å2
3----0.24 Å2
Refinement stepCycle: LAST / Resolution: 1.91→24.09 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1101 0 15 99 1215
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0130.021165
X-RAY DIFFRACTIONr_bond_other_d0.0010.02817
X-RAY DIFFRACTIONr_angle_refined_deg1.4711.9921562
X-RAY DIFFRACTIONr_angle_other_deg0.95132006
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.9595132
X-RAY DIFFRACTIONr_dihedral_angle_2_deg38.09625.63655
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.96915202
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.329154
X-RAY DIFFRACTIONr_chiral_restr0.0880.2168
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0211238
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02216
LS refinement shellResolution: 1.91→1.959 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.437 30 -
Rwork0.352 656 -
all-686 -
obs--100 %
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)
11.1386-0.3307-0.41150.33150.12160.8215-0.1162-0.0146-0.22360.05920.02160.05970.0987-0.00430.09460.0701-0.00770.0190.02470.01840.060237.95932.575710.6343
20.5216-0.0637-0.22010.32360.48330.86710.0016-0.0677-0.0260.0599-0.02660.02720.07370.04610.0250.0767-0.00830.00570.0548-0.00470.048238.484739.783413.6362
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A42 - 90
2X-RAY DIFFRACTION2A91 - 168

+
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