[English] 日本語
Yorodumi
- PDB-7mcf: CRYSTAL STRUCTURE OF THE FIRST BROMODOMAIN OF HUMAN BRD4 IN COMPL... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7mcf
TitleCRYSTAL STRUCTURE OF THE FIRST BROMODOMAIN OF HUMAN BRD4 IN COMPLEX WITH 2-{3-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-6-fluoro-5-[(S)-(3-fluoropyridin-2-yl)(oxan-4-yl)methyl]-5H-pyrido[3,2-b]indol-7-yl}propan-2-ol
ComponentsBromodomain-containing protein 4
KeywordsCELL CYCLE / BROMODOMAIN-CONTAINING PROTEIN 4 ISOFORM LONG / BRD4 / BROMODOMAIN CONTAINING PROTEIN 4 / CAP / HUNK1 / MCAP / MITOTIC CHROMOSOME ASSOCIATED PROTEIN SGC
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 / histone reader activity / RNA polymerase II CTD heptapeptide repeat kinase 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 / 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 / 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 / NET domain superfamily / NET domain profile. / Brdt, bromodomain, repeat II / Brdt, bromodomain, repeat I / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain, conserved site / Bromodomain signature. ...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, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily
Similarity search - Domain/homology
Chem-YX4 / Bromodomain-containing protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.19 Å
AuthorsSheriff, S.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2021
Title: Development of BET inhibitors as potential treatments for cancer: A search for structural diversity.
Authors: Hill, M.D. / Fang, H. / Tokarski, J. / Fanslau, C. / Haarhoff, Z. / Huang, C. / Kramer, M. / Menard, K. / Monereau, L. / Morrison, J. / Ranasinghe, A. / Shields, E.E. / Tye, C.K. / ...Authors: Hill, M.D. / Fang, H. / Tokarski, J. / Fanslau, C. / Haarhoff, Z. / Huang, C. / Kramer, M. / Menard, K. / Monereau, L. / Morrison, J. / Ranasinghe, A. / Shields, E.E. / Tye, C.K. / Westhouse, R. / Everlof, G. / Sheriff, S. / Yan, C. / Marsilio, F. / Zhang, L. / Zvyaga, T. / Lee, F. / Gavai, A.V. / Degnan, A.P.
History
DepositionApr 2, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 26, 2021Provider: repository / Type: Initial release
Revision 1.1Jun 2, 2021Group: Database references / Category: citation / Item: _citation.journal_volume
Revision 1.2Oct 18, 2023Group: 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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)31,4804
Polymers30,4152
Non-polymers1,0652
Water1,69394
1
A: Bromodomain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)16,2733
Polymers15,2071
Non-polymers1,0652
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Bromodomain-containing protein 4


Theoretical massNumber of molelcules
Total (without water)15,2071
Polymers15,2071
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)87.912, 89.356, 36.554
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212

-
Components

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


Mass: 15207.499 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Plasmid: PET28 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: O60885
#2: Chemical ChemComp-YX4 / 2-{3-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-6-fluoro-5-[(S)-(3-fluoropyridin-2-yl)(oxan-4-yl)methyl]-5H-pyrido[3,2-b]indol-7-yl}propan-2-ol


Mass: 532.584 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C29H30F2N6O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 94 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.36 Å3/Da / Density % sol: 47.89 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7
Details: 100 mM Tris, PH 7.0, 100 mM NaCl, 30%(w/v) PEG 3000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 26, 2015
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.19→43.96 Å / Num. obs: 15428 / % possible obs: 99.8 % / Observed criterion σ(I): 0 / Redundancy: 5.9 % / Biso Wilson estimate: 35.49 Å2 / Rsym value: 0.087 / Net I/σ(I): 14.3
Reflection shellResolution: 2.19→2.68 Å / Redundancy: 5.6 % / Mean I/σ(I) obs: 5.5 / Num. unique obs: 6871 / Rsym value: 0.301 / % possible all: 99.7

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
XDSdata reduction
Aimlessdata scaling
PHASERphasing
BUSTER2.11.6refinement
PDB_EXTRACT3.22data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3UVW

3uvw


Resolution: 2.19→19.89 Å / Cor.coef. Fo:Fc: 0.9244 / Cor.coef. Fo:Fc free: 0.9081 / SU R Cruickshank DPI: 0.229 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.237 / SU Rfree Blow DPI: 0.184 / SU Rfree Cruickshank DPI: 0.181
RfactorNum. reflection% reflectionSelection details
Rfree0.2337 709 4.62 %RANDOM
Rwork0.2041 ---
obs0.2055 15361 99.46 %-
Displacement parametersBiso max: 82.17 Å2 / Biso mean: 30.47 Å2 / Biso min: 9.91 Å2
Baniso -1Baniso -2Baniso -3
1--2.997 Å20 Å20 Å2
2--4.0195 Å20 Å2
3----1.0225 Å2
Refine analyzeLuzzati coordinate error obs: 0.31 Å
Refinement stepCycle: final / Resolution: 2.19→19.89 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1767 0 78 94 1939
Biso mean--25.75 37.85 -
Num. residues----216
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d643SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes56HARMONIC2
X-RAY DIFFRACTIONt_gen_planes341HARMONIC5
X-RAY DIFFRACTIONt_it1961HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion240SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact2405SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d1961HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg2737HARMONIC21.02
X-RAY DIFFRACTIONt_omega_torsion3.18
X-RAY DIFFRACTIONt_other_torsion15.94
LS refinement shellResolution: 2.19→2.34 Å / Total num. of bins used: 8
RfactorNum. reflection% reflection
Rfree0.2668 133 4.98 %
Rwork0.2003 2540 -
all0.2035 2673 -
obs--97.66 %

+
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://pdbjlvh1.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