[English] 日本語
Yorodumi
- PDB-8wyg: Crystal Structure of the second bromodomain of human BRD2 in comp... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8wyg
TitleCrystal Structure of the second bromodomain of human BRD2 in complex with the inhibitor 22
ComponentsBromodomain-containing protein 2
KeywordsPROTEIN BINDING / BRD2(2) / Bromodomain
Function / homology
Function and homology information


histone H4K12ac reader activity / histone H4K5ac reader activity / histone H3K14ac reader activity / acetylation-dependent protein binding / chromatin looping / RUNX3 regulates p14-ARF / positive regulation of T-helper 17 cell lineage commitment / protein localization to chromatin / neural tube closure / nucleosome assembly ...histone H4K12ac reader activity / histone H4K5ac reader activity / histone H3K14ac reader activity / acetylation-dependent protein binding / chromatin looping / RUNX3 regulates p14-ARF / positive regulation of T-helper 17 cell lineage commitment / protein localization to chromatin / neural tube closure / nucleosome assembly / histone binding / spermatogenesis / nuclear speck / chromatin remodeling / protein serine/threonine kinase activity / chromatin binding / regulation of transcription by RNA polymerase II / chromatin / nucleoplasm / nucleus / cytoplasm
Similarity search - Function
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 ...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 / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily
Similarity search - Domain/homology
Chem-XHN / Bromodomain-containing protein 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.13 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 2
B: Bromodomain-containing protein 2
C: Bromodomain-containing protein 2
D: Bromodomain-containing protein 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)66,1318
Polymers63,9254
Non-polymers2,2074
Water181
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)91.782, 95.497, 109.080
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein
Bromodomain-containing protein 2 / O27.1.1 / Really interesting new gene 3 protein


Mass: 15981.218 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRD2, KIAA9001, RING3 / Production host: Escherichia coli (E. coli) / References: UniProt: P25440
#2: Chemical
ChemComp-XHN / 2-[[5-[2-(4-fluoranyl-2,6-dimethyl-phenoxy)-5-(2-oxidanylpropan-2-yl)phenyl]-1-methyl-2-oxidanylidene-pyridin-4-yl]amino]-~{N}-(4-oxidanylcyclohexyl)ethanamide


Mass: 551.649 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C31H38FN3O5 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 1 / 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: 3.74 Å3/Da / Density % sol: 67.1 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / Details: 60% v/v Tacsimate pH 7.0

-
Data collection

DiffractionMean temperature: 80 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL02U1 / Wavelength: 0.97918 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Sep 24, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 3.13→109.08 Å / Num. obs: 17520 / % possible obs: 100 % / Redundancy: 6 % / CC1/2: 0.951 / Rmerge(I) obs: 0.364 / Rpim(I) all: 0.163 / Rrim(I) all: 0.4 / Net I/σ(I): 5.9 / Num. measured all: 104944
Reflection shellResolution: 3.13→3.35 Å / % possible obs: 100 % / Redundancy: 6.2 % / Rmerge(I) obs: 0.726 / Num. measured all: 19315 / Num. unique obs: 3115 / CC1/2: 0.717 / Rpim(I) all: 0.317 / Rrim(I) all: 0.794 / Net I/σ(I) obs: 1.9

-
Processing

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

7wni


Resolution: 3.13→71.85 Å / Cor.coef. Fo:Fc: 0.93 / Cor.coef. Fo:Fc free: 0.872 / SU B: 19.374 / SU ML: 0.325 / Cross valid method: THROUGHOUT / ESU R: 1.03 / ESU R Free: 0.392 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.25677 931 5.3 %RANDOM
Rwork0.19452 ---
obs0.19786 16542 99.93 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 51.416 Å2
Baniso -1Baniso -2Baniso -3
1-3.91 Å20 Å20 Å2
2---1.4 Å20 Å2
3----2.51 Å2
Refinement stepCycle: 1 / Resolution: 3.13→71.85 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3631 0 160 1 3792
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0150.0193903
X-RAY DIFFRACTIONr_bond_other_d0.0040.023595
X-RAY DIFFRACTIONr_angle_refined_deg1.7641.9985273
X-RAY DIFFRACTIONr_angle_other_deg1.1233.0138337
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.0245435
X-RAY DIFFRACTIONr_dihedral_angle_2_deg32.73423.404188
X-RAY DIFFRACTIONr_dihedral_angle_3_deg19.17215676
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.5491524
X-RAY DIFFRACTIONr_chiral_restr0.0870.2523
X-RAY DIFFRACTIONr_gen_planes_refined0.0070.0214221
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02827
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_it3.1634.9411764
X-RAY DIFFRACTIONr_mcbond_other3.1624.9411765
X-RAY DIFFRACTIONr_mcangle_it5.1217.42191
X-RAY DIFFRACTIONr_mcangle_other5.127.42192
X-RAY DIFFRACTIONr_scbond_it3.7075.3022139
X-RAY DIFFRACTIONr_scbond_other3.7065.3012140
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other6.1427.7453083
X-RAY DIFFRACTIONr_long_range_B_refined8.69455.6654597
X-RAY DIFFRACTIONr_long_range_B_other8.69355.6664598
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 3.13→3.211 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.356 73 -
Rwork0.294 1204 -
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