[English] 日本語
Yorodumi
- PDB-6ufx: WD repeat-containing protein 5 complexed with N-[(3,5-dimethoxyph... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ufx
TitleWD repeat-containing protein 5 complexed with N-[(3,5-dimethoxyphenyl)methyl]-4'-fluoro-5-{[(2E)-2-imino-3-methyl-2,3-dihydro-1H-imidazol-1-yl]methyl}-2'-methyl[1,1'-biphenyl]-3-carboxamide (compound 13)
ComponentsWD repeat-containing protein 5
KeywordsGENE REGULATION/INHIBITOR / inhibitor / GENE REGULATION-INHIBITOR complex
Function / homology
Function and homology information


Epigenetic regulation of gene expression by MLL3 and MLL4 complexes / MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Cardiogenesis / histone methyltransferase complex / Formation of WDR5-containing histone-modifying complexes ...Epigenetic regulation of gene expression by MLL3 and MLL4 complexes / MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Cardiogenesis / histone methyltransferase complex / Formation of WDR5-containing histone-modifying complexes / regulation of cell division / regulation of embryonic development / MLL1 complex / histone acetyltransferase complex / : / positive regulation of gluconeogenesis / transcription initiation-coupled chromatin remodeling / gluconeogenesis / skeletal system development / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / PKMTs methylate histone lysines / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / mitotic spindle / HATs acetylate histones / Neddylation / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / histone binding / regulation of cell cycle / regulation of DNA-templated transcription / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / nucleoplasm / nucleus
Similarity search - Function
YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats ...YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Mainly Beta
Similarity search - Domain/homology
Chem-Q6S / WD repeat-containing protein 5
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.015 Å
AuthorsRietz, T.A. / Fesik, S.W. / Zhao, B.
Funding support United States, 3items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)HHSN261200800001E United States
National Institutes of Health/National Cancer Institute (NIH/NCI)CA200709 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)CA68485 United States
CitationJournal: J.Med.Chem. / Year: 2020
Title: Discovery and Structure-Based Optimization of Potent and Selective WD Repeat Domain 5 (WDR5) Inhibitors Containing a Dihydroisoquinolinone Bicyclic Core.
Authors: Tian, J. / Teuscher, K.B. / Aho, E.R. / Alvarado, J.R. / Mills, J.J. / Meyers, K.M. / Gogliotti, R.D. / Han, C. / Macdonald, J.D. / Sai, J. / Shaw, J.G. / Sensintaffar, J.L. / Zhao, B. / ...Authors: Tian, J. / Teuscher, K.B. / Aho, E.R. / Alvarado, J.R. / Mills, J.J. / Meyers, K.M. / Gogliotti, R.D. / Han, C. / Macdonald, J.D. / Sai, J. / Shaw, J.G. / Sensintaffar, J.L. / Zhao, B. / Rietz, T.A. / Thomas, L.R. / Payne, W.G. / Moore, W.J. / Stott, G.M. / Kondo, J. / Inoue, M. / Coffey, R.J. / Tansey, W.P. / Stauffer, S.R. / Lee, T. / Fesik, S.W.
History
DepositionSep 25, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 1, 2020Provider: repository / Type: Initial release
Revision 1.1Jan 15, 2020Group: Database references / Category: citation / citation_author
Item: _citation.title / _citation.year ..._citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.2Feb 5, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.3Oct 11, 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: WD repeat-containing protein 5
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,8392
Polymers33,3511
Non-polymers4891
Water2,540141
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area10880 Å2
MethodPISA
Unit cell
Length a, b, c (Å)78.625, 98.896, 80.546
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number20
Space group name H-MC2221
Components on special symmetry positions
IDModelComponents
11A-526-

HOH

-
Components

#1: Protein WD repeat-containing protein 5 / BMP2-induced 3-kb gene protein


Mass: 33350.789 Da / Num. of mol.: 1 / Fragment: UNP residues 32-334
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: WDR5, BIG3 / Production host: Escherichia coli (E. coli) / References: UniProt: P61964
#2: Chemical ChemComp-Q6S / N-[(3,5-dimethoxyphenyl)methyl]-4'-fluoro-5-{[(2E)-2-imino-3-methyl-2,3-dihydro-1H-imidazol-1-yl]methyl}-2'-methyl[1,1'-biphenyl]-3-carboxamide


Mass: 488.553 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H29FN4O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 141 / 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: 2.35 Å3/Da / Density % sol: 47.6 %
Crystal growTemperature: 291 K / Method: vapor diffusion, sitting drop
Details: 0.1 M Bis-Tris or HEPES or Tris-HCl, pH 6.0-8.0, 0.2 M ammonium acetate, 20-30% PEG3350
PH range: 6.0-8.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 0.987 Å
DetectorType: RAYONIX MX300HE / Detector: CCD / Date: Apr 10, 2019
RadiationMonochromator: diamond(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.987 Å / Relative weight: 1
ReflectionResolution: 2→30 Å / Num. obs: 20876 / % possible obs: 100 % / Redundancy: 12.1 % / CC1/2: 0.998 / Rmerge(I) obs: 0.162 / Rpim(I) all: 0.048 / Rrim(I) all: 0.169 / Rsym value: 0.108 / Net I/σ(I): 19.6
Reflection shellResolution: 2→2.03 Å / Rmerge(I) obs: 1.035 / Mean I/σ(I) obs: 3.41 / Num. unique obs: 1005 / CC1/2: 0.762 / Rpim(I) all: 0.319 / Rrim(I) all: 1.085 / Rsym value: 1.032

-
Processing

Software
NameVersionClassification
PHENIX1.15.2_3472refinement
PDB_EXTRACT3.25data extraction
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB entry 3EG6

3eg6


Resolution: 2.015→28.746 Å / SU ML: 0.21 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 21.09
RfactorNum. reflection% reflection
Rfree0.2083 1040 4.99 %
Rwork0.1691 --
obs0.171 20848 98.84 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 68.56 Å2 / Biso mean: 23.091 Å2 / Biso min: 10.9 Å2
Refinement stepCycle: final / Resolution: 2.015→28.746 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2267 0 36 141 2444
Biso mean--23.51 30.83 -
Num. residues----303
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.015-2.12110.27881440.206258192
2.1211-2.25390.24281350.18972849100
2.2539-2.42790.24631460.18662819100
2.4279-2.6720.22481640.18262827100
2.672-3.05830.20381600.16992831100
3.0583-3.85170.19991270.15372914100
3.8517-28.7460.17371640.15652987100

+
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