[English] 日本語
Yorodumi
- PDB-4e96: Crystal Structure of the first bromodomain of human BRD4 in compl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4.0E+96
TitleCrystal Structure of the first bromodomain of human BRD4 in complex with the inhibitor PFi-1
ComponentsBromodomain-containing protein 4
KeywordsPROTEIN BINDING/INHIBITOR / BROMODOMAIN / CAP / HUNK1 / MCAP / MITOTIC CHROMOSOME ASSOCIATED PROTEIN / JQ1 / BETSOFF1 / STRUCTURAL GENOMICS CONSORTIUM / SGC / CELL CYCLE / PROTEIN BINDING-INHIBITOR 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 / positive regulation of G2/M transition of mitotic cell cycle / RNA polymerase II CTD heptapeptide repeat kinase activity / histone reader activity / condensed nuclear chromosome / positive regulation of transcription elongation by RNA polymerase II ...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 / positive regulation of G2/M transition of mitotic cell cycle / RNA polymerase II CTD heptapeptide repeat kinase activity / histone reader activity / condensed nuclear chromosome / positive regulation of transcription elongation by RNA polymerase II / transcription coregulator activity / lysine-acetylated histone binding / p53 binding / 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 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 / 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 / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-0NS / Bromodomain-containing protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.92 Å
AuthorsFilippakopoulos, P. / Picaud, S. / Felletar, I. / Fedorov, O. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Weigelt, J. / Fish, P. / Bunnage, M. ...Filippakopoulos, P. / Picaud, S. / Felletar, I. / Fedorov, O. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Weigelt, J. / Fish, P. / Bunnage, M. / Owen, D. / Knapp, S. / Cook, A. / Structural Genomics Consortium (SGC)
CitationJournal: J.Med.Chem. / Year: 2012
Title: Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit.
Authors: Fish, P.V. / Filippakopoulos, P. / Bish, G. / Brennan, P.E. / Bunnage, M.E. / Cook, A.S. / Federov, O. / Gerstenberger, B.S. / Jones, H. / Knapp, S. / Marsden, B. / Nocka, K. / Owen, D.R. / ...Authors: Fish, P.V. / Filippakopoulos, P. / Bish, G. / Brennan, P.E. / Bunnage, M.E. / Cook, A.S. / Federov, O. / Gerstenberger, B.S. / Jones, H. / Knapp, S. / Marsden, B. / Nocka, K. / Owen, D.R. / Philpott, M. / Picaud, S. / Primiano, M.J. / Ralph, M.J. / Sciammetta, N. / Trzupek, J.D.
History
DepositionMar 20, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 18, 2012Provider: repository / Type: Initial release
Revision 1.1Nov 14, 2012Group: Database references
Revision 1.2Feb 27, 2013Group: Database references
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 / 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 / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
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)15,6105
Polymers15,0991
Non-polymers5114
Water1,08160
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)34.710, 46.710, 78.250
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

-
Protein , 1 types, 1 molecules A

#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

-
Non-polymers , 5 types, 64 molecules

#2: Chemical ChemComp-0NS / 2-methoxy-N-(3-methyl-2-oxo-1,2,3,4-tetrahydroquinazolin-6-yl)benzenesulfonamide


Mass: 347.389 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H17N3O4S
#3: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Na
#4: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#5: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


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


Mass: 18.015 Da / Num. of mol.: 60 / 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: 2.1 Å3/Da / Density % sol: 41.44 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: 0.2M Na(malonate) 0.1M BTProp pH 8.5 20% PEG3350 10% EtGly, VAPOR DIFFUSION, SITTING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.54178 Å
DetectorType: RIGAKU RAXIS IV / Detector: IMAGE PLATE / Date: May 13, 2011
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54178 Å / Relative weight: 1
ReflectionRedundancy: 4.6 % / Av σ(I) over netI: 5.6 / Number: 47459 / Rsym value: 0.11 / D res high: 1.91 Å / D res low: 19.572 Å / Num. obs: 10412 / % possible obs: 99.5
Diffraction reflection shell
Highest resolution (Å)Lowest resolution (Å)% possible obs (%)IDRmerge(I) obsRsym valueRedundancy
6.0419.5797.110.0430.0434
4.276.0499.910.050.054.3
3.494.2799.710.0550.0554.5
3.023.4999.910.080.084.5
2.73.0299.810.1140.1144.6
2.472.799.710.1770.1774.6
2.282.4799.610.2450.2454.6
2.142.2899.710.320.324.6
2.012.1499.110.4610.4614.6
1.912.019910.8190.8194.6
ReflectionResolution: 1.91→23.355 Å / Num. all: 10464 / Num. obs: 10412 / % possible obs: 99.5 % / Redundancy: 4.6 % / Biso Wilson estimate: 26.5 Å2 / Rmerge(I) obs: 0.11 / Rsym value: 0.11 / Net I/σ(I): 8.8
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allRsym value% possible all
1.91-2.014.60.8190.9685214790.81999
2.01-2.144.60.4611.7644513940.46199.1
2.14-2.284.60.322.4611713240.3299.7
2.28-2.474.60.2453.2576412430.24599.6
2.47-2.74.60.1774.3534011580.17799.7
2.7-3.024.60.1146.4479410420.11499.8
3.02-3.494.50.088.242869520.0899.9
3.49-4.274.50.05511.235737990.05599.7
4.27-6.044.30.0511.227956460.0599.9
6.04-19.57240.0439.514933750.04397.1

-
Phasing

PhasingMethod: molecular replacement
Phasing MRRfactor: 53.92 / Model details: Phaser MODE: MR_AUTO
Highest resolutionLowest resolution
Rotation2.5 Å23.35 Å
Translation2.5 Å23.35 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: PDB ENTRY 2OSS

2oss


Resolution: 1.92→23.35 Å / Cor.coef. Fo:Fc: 0.946 / Cor.coef. Fo:Fc free: 0.926 / WRfactor Rfree: 0.2612 / WRfactor Rwork: 0.1933 / Occupancy max: 1 / Occupancy min: 0.3 / FOM work R set: 0.8007 / SU B: 5.24 / SU ML: 0.148 / SU R Cruickshank DPI: 0.1869 / SU Rfree: 0.1821 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.196 / ESU R Free: 0.192 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES: REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2855 489 4.8 %RANDOM
Rwork0.2126 ---
all0.2159 10208 --
obs0.2159 10125 99.19 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso max: 94.93 Å2 / Biso mean: 28.7881 Å2 / Biso min: 9.25 Å2
Baniso -1Baniso -2Baniso -3
1-4 Å20 Å20 Å2
2---2.1 Å20 Å2
3----1.9 Å2
Refinement stepCycle: LAST / Resolution: 1.92→23.35 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1020 0 33 60 1113
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0160.0221107
X-RAY DIFFRACTIONr_bond_other_d0.0010.02745
X-RAY DIFFRACTIONr_angle_refined_deg1.5121.9971513
X-RAY DIFFRACTIONr_angle_other_deg0.9913.0021827
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.8495126
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.10626.15452
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.52415185
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.075152
X-RAY DIFFRACTIONr_chiral_restr0.0790.2161
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.0211195
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02193
X-RAY DIFFRACTIONr_mcbond_it4.2513644
X-RAY DIFFRACTIONr_mcbond_other1.4213241
X-RAY DIFFRACTIONr_mcangle_it5.55651061
X-RAY DIFFRACTIONr_scbond_it8.4358463
X-RAY DIFFRACTIONr_scangle_it9.94111452
LS refinement shellResolution: 1.92→1.97 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.436 45 -
Rwork0.38 665 -
all-710 -
obs--98.07 %

+
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