[English] 日本語
Yorodumi
- PDB-9dlw: Crystal structure of the ternary complex of DCAF1 and WDR5 with P... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9dlw
TitleCrystal structure of the ternary complex of DCAF1 and WDR5 with PROTAC, OICR-41114
Components
  • DDB1- and CUL4-associated factor 1
  • WD repeat-containing protein 5
KeywordsPROTEIN BINDING / E3 ligase / adaptor / PROTAC / WDR / ternary complex
Function / homology
Function and homology information


cell competition in a multicellular organism / histone H2AT120 kinase activity / histone H3Q5ser reader activity / histone H3K4me1 reader activity / V(D)J recombination / Epigenetic regulation of gene expression by MLL3 and MLL4 complexes / MLL3/4 complex / Set1C/COMPASS complex / MLL1/2 complex / ATAC complex ...cell competition in a multicellular organism / histone H2AT120 kinase activity / histone H3Q5ser reader activity / histone H3K4me1 reader activity / V(D)J recombination / 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 / Cul4-RING E3 ubiquitin ligase complex / Formation of WDR5-containing histone-modifying complexes / histone methyltransferase complex / regulation of cell division / MLL1 complex / regulation of embryonic development / histone acetyltransferase complex / ubiquitin-like ligase-substrate adaptor activity / positive regulation of gluconeogenesis / transcription initiation-coupled chromatin remodeling / post-translational protein modification / B cell differentiation / nuclear estrogen receptor binding / 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 / fibrillar center / positive regulation of protein catabolic process / mitotic spindle / Antigen processing: Ubiquitination & Proteasome degradation / HATs acetylate histones / Neddylation / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / histone binding / proteasome-mediated ubiquitin-dependent protein catabolic process / non-specific serine/threonine protein kinase / regulation of cell cycle / protein ubiquitination / protein serine kinase activity / centrosome / 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 / ATP binding / nucleus / cytoplasm
Similarity search - Function
VPRBP/DCAF1 family / Lissencephaly type-1-like homology motif / WDR5 beta-propeller domain / LIS1 homology (LisH) motif profile. / LIS1 homology motif / Armadillo-like helical / Armadillo-type fold / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. ...VPRBP/DCAF1 family / Lissencephaly type-1-like homology motif / WDR5 beta-propeller domain / LIS1 homology (LisH) motif profile. / LIS1 homology motif / Armadillo-like helical / Armadillo-type fold / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / 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
Similarity search - Domain/homology
: / WD repeat-containing protein 5 / DDB1- and CUL4-associated factor 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.07 Å
AuthorsMabanglo, M.F. / Mamai, A. / Wilson, B.J. / Hoffer, L. / Al-awar, R. / Vedadi, M.
Funding support Canada, 1items
OrganizationGrant numberCountry
Ontario Institute for Cancer Research Canada
CitationJournal: Nat Commun / Year: 2024
Title: Crystal structures of DCAF1-PROTAC-WDR5 ternary complexes provide insight into DCAF1 substrate specificity.
Authors: Mabanglo, M.F. / Wilson, B. / Noureldin, M. / Kimani, S.W. / Mamai, A. / Krausser, C. / Gonzalez-Alvarez, H. / Srivastava, S. / Mohammed, M. / Hoffer, L. / Chan, M. / Avrumutsoae, J. / Li, A. ...Authors: Mabanglo, M.F. / Wilson, B. / Noureldin, M. / Kimani, S.W. / Mamai, A. / Krausser, C. / Gonzalez-Alvarez, H. / Srivastava, S. / Mohammed, M. / Hoffer, L. / Chan, M. / Avrumutsoae, J. / Li, A.S.M. / Hajian, T. / Tucker, S. / Green, S. / Szewczyk, M. / Barsyte-Lovejoy, D. / Santhakumar, V. / Ackloo, S. / Loppnau, P. / Li, Y. / Seitova, A. / Kiyota, T. / Wang, J.G. / Prive, G.G. / Kuntz, D.A. / Patel, B. / Rathod, V. / Vala, A. / Rout, B. / Aman, A. / Poda, G. / Uehling, D. / Ramnauth, J. / Halabelian, L. / Marcellus, R. / Al-Awar, R. / Vedadi, M.
History
DepositionSep 11, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 6, 2024Provider: repository / Type: Initial release
Revision 1.1Dec 4, 2024Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
B: DDB1- and CUL4-associated factor 1
A: WD repeat-containing protein 5
hetero molecules


Theoretical massNumber of molelcules
Total (without water)76,2073
Polymers74,7322
Non-polymers1,4751
Water7,548419
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: surface plasmon resonance
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)80.225, 83.882, 131.483
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

#1: Protein DDB1- and CUL4-associated factor 1 / HIV-1 Vpr-binding protein / VprBP / Serine/threonine-protein kinase VPRBP / Vpr-interacting protein


Mass: 38298.820 Da / Num. of mol.: 1 / Fragment: residues 1080-1390
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DCAF1, KIAA0800, RIP, VPRBP / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q9Y4B6, non-specific serine/threonine protein kinase
#2: Protein WD repeat-containing protein 5 / BMP2-induced 3-kb gene protein


Mass: 36433.207 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: WDR5, BIG3 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P61964
#3: Chemical ChemComp-A1BAF / N-{(1P)-5'-({(32E)-33-[(3P)-4-{[(1S)-3-amino-1-(3-chloro-4-fluorophenyl)-3-oxopropyl]carbamoyl}-3-(4-chloro-2-fluorophenyl)-1H-pyrrol-2-yl]-31-oxo-3,6,9,12,15,18,21,24,27-nonaoxa-30-azatritriacont-32-en-1-yl}carbamoyl)-2'-fluoro-4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl][1,1'-biphenyl]-3-yl}-6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide / OICR-41114


Mass: 1475.356 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C70H83Cl2F6N9O15 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 419 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.96 Å3/Da / Density % sol: 58.44 %
Crystal growTemperature: 294 K / Method: vapor diffusion, sitting drop / pH: 6.9
Details: 1.8 M Sodium phosphate monobasic monohydrate, potassium phosphate dibasic / pH 6.9

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-002+ / Wavelength: 1.54189 Å
DetectorType: DECTRIS EIGER R 1M / Detector: PIXEL / Date: Jun 21, 2024
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54189 Å / Relative weight: 1
ReflectionResolution: 2.07→28.59 Å / Num. obs: 52605 / % possible obs: 95.8 % / Redundancy: 4.4 % / Biso Wilson estimate: 17.3 Å2 / CC1/2: 0.989 / CC star: 0.997 / Net I/σ(I): 7.69
Reflection shellResolution: 2.07→2.11 Å / Num. unique obs: 2423 / CC1/2: 0.448 / CC star: 0.997

-
Processing

Software
NameVersionClassification
PHENIX1.21.1_5286refinement
CrysalisProdata reduction
Aimlessdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.07→28.59 Å / SU ML: 0.2731 / Cross valid method: FREE R-VALUE / σ(F): 1.33 / Phase error: 24.6376
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2422 2645 5.04 %
Rwork0.1997 49820 -
obs0.2018 52465 95.8 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 20.66 Å2
Refinement stepCycle: LAST / Resolution: 2.07→28.59 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4833 0 102 419 5354
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01135088
X-RAY DIFFRACTIONf_angle_d0.95566907
X-RAY DIFFRACTIONf_chiral_restr0.0563758
X-RAY DIFFRACTIONf_plane_restr0.0067874
X-RAY DIFFRACTIONf_dihedral_angle_d14.38021824
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.07-2.110.37221290.28322289X-RAY DIFFRACTION84.19
2.11-2.150.31451310.25422358X-RAY DIFFRACTION88.67
2.15-2.190.291400.26732479X-RAY DIFFRACTION91.51
2.19-2.240.38371310.35142477X-RAY DIFFRACTION91.93
2.24-2.290.41531290.38482494X-RAY DIFFRACTION92.59
2.29-2.350.36151460.28122537X-RAY DIFFRACTION94.31
2.35-2.410.26051460.21792639X-RAY DIFFRACTION97.38
2.41-2.480.28141320.21982697X-RAY DIFFRACTION99.12
2.48-2.560.24581250.20492727X-RAY DIFFRACTION99.76
2.56-2.660.28471570.19482704X-RAY DIFFRACTION99.9
2.66-2.760.2281340.19322729X-RAY DIFFRACTION99.93
2.76-2.890.24261420.18822720X-RAY DIFFRACTION99.97
2.89-3.040.24461300.19342734X-RAY DIFFRACTION99.76
3.04-3.230.24311380.18762745X-RAY DIFFRACTION99.24
3.23-3.480.19461370.17272711X-RAY DIFFRACTION98.96
3.48-3.830.21091680.17352697X-RAY DIFFRACTION98.18
3.83-4.380.15451300.14172710X-RAY DIFFRACTION97.09
4.38-5.510.17221670.13022679X-RAY DIFFRACTION96.15
5.51-28.590.20321330.1682694X-RAY DIFFRACTION91.64

+
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