[English] 日本語
Yorodumi
- PDB-8wy3: Crystal Structure of the first bromodomain of human BRD4 in compl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8wy3
TitleCrystal Structure of the first bromodomain of human BRD4 in complex with the inhibitor 21
ComponentsBromodomain-containing protein 4
KeywordsPROTEIN BINDING / BRD4(1) / Bromodomain
Function / homology
Function and homology information


RNA polymerase II C-terminal domain binding / P-TEFb complex binding / negative regulation of DNA damage checkpoint / host-mediated suppression 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 / condensed nuclear chromosome / histone reader activity / : ...RNA polymerase II C-terminal domain binding / P-TEFb complex binding / negative regulation of DNA damage checkpoint / host-mediated suppression 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 / condensed nuclear chromosome / histone reader activity / : / positive regulation of transcription elongation by RNA polymerase II / transcription coregulator activity / p53 binding / chromosome / regulation of inflammatory response / histone binding / Potential therapeutics for SARS / positive regulation of canonical NF-kappaB signal transduction / transcription coactivator activity / transcription cis-regulatory region binding / chromatin remodeling / 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 / 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, conserved site ...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, conserved site / Bromodomain signature. / Bromodomain / Bromodomain (BrD) profile. / bromo domain / Bromodomain / Bromodomain-like superfamily
Similarity search - Domain/homology
Chem-XHE / Bromodomain-containing protein 4
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.78 Å
AuthorsXu, H. / Zhao, X. / Shen, H. / Xu, Y. / Wu, X.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)22307116 China
CitationJournal: J.Med.Chem. / Year: 2024
Title: Discovery of Novel Phenoxyaryl Pyridones as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with High Selectivity for the Second Bromodomain (BD2) to Potentially Treat Acute Myeloid Leukemia.
Authors: Jiang, W. / Hou, Q. / Xu, H. / Yang, K. / Wang, X. / Zhang, K. / Zeng, Y. / Li, W. / Wang, B. / Luo, G. / Zhao, X. / Shen, H. / Xu, Y. / Wu, X.
History
DepositionOct 30, 2023Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jan 24, 2024Provider: repository / Type: Initial release
Revision 1.1Feb 7, 2024Group: Database references / Refinement description
Category: citation / citation_author ...citation / citation_author / pdbx_initial_refinement_model / refine
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID / _pdbx_initial_refinement_model.entity_id_list / _refine.pdbx_starting_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Bromodomain-containing protein 4
B: Bromodomain-containing protein 4
C: Bromodomain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)51,7836
Polymers50,3023
Non-polymers1,4813
Water34219
1
B: Bromodomain-containing protein 4
C: Bromodomain-containing protein 4
hetero molecules

A: Bromodomain-containing protein 4
hetero molecules


Theoretical massNumber of molelcules
Total (without water)51,7836
Polymers50,3023
Non-polymers1,4813
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation10_554-y,-x,-z-1/61
Unit cell
Length a, b, c (Å)140.409, 140.409, 134.482
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number178
Space group name H-MP6122

-
Components

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


Mass: 16767.326 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Production host: Escherichia coli (E. coli) / References: UniProt: O60885
#2: Chemical ChemComp-XHE / ~{N}-cyclopropyl-2-[[5-[2-(4-fluoranyl-2,6-dimethyl-phenoxy)-5-(2-oxidanylpropan-2-yl)phenyl]-1-methyl-2-oxidanylidene-pyridin-4-yl]amino]ethanamide


Mass: 493.570 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C28H32FN3O4 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 19 / 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: 3.8 Å3/Da / Density % sol: 67.66 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8.5 / Details: 2.0 M Sodium formate, 0.1 M Tris pH 8.5

-
Data collection

DiffractionMean temperature: 80 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL10U2 / Wavelength: 0.97918 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 16, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 2.78→134.48 Å / Num. obs: 19675 / % possible obs: 97 % / Redundancy: 15.6 % / CC1/2: 0.996 / Rmerge(I) obs: 0.224 / Rpim(I) all: 0.058 / Rrim(I) all: 0.232 / Net I/σ(I): 9 / Num. measured all: 307458
Reflection shellResolution: 2.78→2.93 Å / % possible obs: 100 % / Redundancy: 14.4 % / Rmerge(I) obs: 1.289 / Num. measured all: 41839 / Num. unique obs: 2897 / CC1/2: 0.858 / Rpim(I) all: 0.349 / Rrim(I) all: 1.337 / Net I/σ(I) obs: 2.3

-
Processing

Software
NameVersionClassification
REFMAC5.8.0189refinement
Aimlessdata scaling
XDSdata reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 7wjs

7wjs


Resolution: 2.78→121.6 Å / Cor.coef. Fo:Fc: 0.957 / Cor.coef. Fo:Fc free: 0.936 / SU B: 12.932 / SU ML: 0.226 / Cross valid method: THROUGHOUT / ESU R: 0.346 / ESU R Free: 0.265 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.2336 939 4.8 %RANDOM
Rwork0.18576 ---
obs0.18797 18692 96.95 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 63.77 Å2
Baniso -1Baniso -2Baniso -3
1--3.15 Å2-1.58 Å2-0 Å2
2---3.15 Å2-0 Å2
3---10.22 Å2
Refinement stepCycle: 1 / Resolution: 2.78→121.6 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2806 0 108 19 2933
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0170.023006
X-RAY DIFFRACTIONr_bond_other_d0.0040.022760
X-RAY DIFFRACTIONr_angle_refined_deg1.9781.9994097
X-RAY DIFFRACTIONr_angle_other_deg1.193.0096428
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.1155331
X-RAY DIFFRACTIONr_dihedral_angle_2_deg39.80225.616146
X-RAY DIFFRACTIONr_dihedral_angle_3_deg20.13715530
X-RAY DIFFRACTIONr_dihedral_angle_4_deg13.148158
X-RAY DIFFRACTIONr_chiral_restr0.1020.2429
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.0213229
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02589
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_it5.1276.1931339
X-RAY DIFFRACTIONr_mcbond_other5.1266.1951340
X-RAY DIFFRACTIONr_mcangle_it7.8789.2561665
X-RAY DIFFRACTIONr_mcangle_other7.8799.2591666
X-RAY DIFFRACTIONr_scbond_it5.4276.6081667
X-RAY DIFFRACTIONr_scbond_other5.4266.6091668
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other8.6819.6862424
X-RAY DIFFRACTIONr_long_range_B_refined11.30768.8513553
X-RAY DIFFRACTIONr_long_range_B_other11.30768.8633554
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2.78→2.852 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.296 59 -
Rwork0.309 1399 -
obs--100 %

+
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