[English] 日本語
Yorodumi
- PDB-5wg6: Human Polycomb Repressive Complex 2 in complex with GSK126 inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5wg6
TitleHuman Polycomb Repressive Complex 2 in complex with GSK126 inhibitor
Components
  • Histone-lysine N-methyltransferase EZH2,Polycomb protein SUZ12 (E.C.2.1.1.43) chimera
  • Polycomb protein EED
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / complex / epigenetics / transferase / inhibitor / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


hepatocyte homeostasis / cellular response to trichostatin A / regulation of gliogenesis / negative regulation of striated muscle cell differentiation / regulation of kidney development / [histone H3]-lysine27 N-trimethyltransferase / sex chromatin / negative regulation of keratinocyte differentiation / histone H3K27 trimethyltransferase activity / negative regulation of retinoic acid receptor signaling pathway ...hepatocyte homeostasis / cellular response to trichostatin A / regulation of gliogenesis / negative regulation of striated muscle cell differentiation / regulation of kidney development / [histone H3]-lysine27 N-trimethyltransferase / sex chromatin / negative regulation of keratinocyte differentiation / histone H3K27 trimethyltransferase activity / negative regulation of retinoic acid receptor signaling pathway / cerebellar cortex development / response to tetrachloromethane / primary miRNA binding / random inactivation of X chromosome / regulatory ncRNA-mediated heterochromatin formation / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / histone H3K27 methyltransferase activity / facultative heterochromatin formation / positive regulation of cell cycle G1/S phase transition / ESC/E(Z) complex / negative regulation of stem cell differentiation / RSC-type complex / pronucleus / chromatin silencing complex / protein-lysine N-methyltransferase activity / cardiac muscle hypertrophy in response to stress / G1 to G0 transition / positive regulation of dendrite development / histone H3 methyltransferase activity / synaptic transmission, GABAergic / DNA methylation-dependent constitutive heterochromatin formation / histone methyltransferase activity / lncRNA binding / negative regulation of G1/S transition of mitotic cell cycle / spinal cord development / negative regulation of gene expression, epigenetic / oligodendrocyte differentiation / Transcriptional Regulation by E2F6 / negative regulation of transcription elongation by RNA polymerase II / negative regulation of cell differentiation / positive regulation of protein serine/threonine kinase activity / subtelomeric heterochromatin formation / ribonucleoprotein complex binding / pericentric heterochromatin / positive regulation of epithelial to mesenchymal transition / RNA polymerase II core promoter sequence-specific DNA binding / nucleosome binding / keratinocyte differentiation / protein localization to chromatin / : / negative regulation of cytokine production involved in inflammatory response / positive regulation of GTPase activity / positive regulation of MAP kinase activity / B cell differentiation / SUMOylation of chromatin organization proteins / enzyme activator activity / hippocampus development / liver regeneration / Regulation of PTEN gene transcription / PRC2 methylates histones and DNA / transcription corepressor binding / Defective pyroptosis / stem cell differentiation / promoter-specific chromatin binding / regulation of circadian rhythm / protein-DNA complex / protein modification process / PKMTs methylate histone lysines / chromatin DNA binding / cellular response to hydrogen peroxide / G1/S transition of mitotic cell cycle / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / transcription corepressor activity / rhythmic process / heterochromatin formation / response to estradiol / chromatin organization / chromosome / Oxidative Stress Induced Senescence / methylation / histone binding / chromosome, telomeric region / cell population proliferation / nuclear body / positive regulation of cell migration / RNA polymerase II cis-regulatory region sequence-specific DNA binding / ribonucleoprotein complex / negative regulation of DNA-templated transcription / positive regulation of cell population proliferation / synapse / chromatin binding / regulation of DNA-templated transcription / chromatin / nucleolus / negative regulation of transcription by RNA polymerase II / RNA binding / zinc ion binding / nucleoplasm / identical protein binding
Similarity search - Function
Polycomb protein SUZ12-like, Zn domain / EZH2, SET domain / Polycomb protein, VEFS-Box / VEFS-Box of polycomb protein / Histone-lysine N-methyltransferase EZH1/EZH2 / Polycomb repressive complex 2 subunit EZH1/EZH2, tri-helical domain / Pre-SET CXC domain / : / WD repeat binding protein EZH2 / Polycomb repressive complex 2 tri-helical domain ...Polycomb protein SUZ12-like, Zn domain / EZH2, SET domain / Polycomb protein, VEFS-Box / VEFS-Box of polycomb protein / Histone-lysine N-methyltransferase EZH1/EZH2 / Polycomb repressive complex 2 subunit EZH1/EZH2, tri-helical domain / Pre-SET CXC domain / : / WD repeat binding protein EZH2 / Polycomb repressive complex 2 tri-helical domain / CXC domain / Ezh2, MCSS domain / Tesmin/TSO1-like CXC domain / Tesmin/TSO1-like CXC domain / CXC domain / Histone-lysine N-methyltransferase EZH1/2-like / CXC domain profile. / : / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain / SET domain / SET domain superfamily / SET domain profile. / SET domain / SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains / SANT/Myb domain / Zinc finger C2H2 type domain signature. / 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
Similarity search - Domain/homology
Chem-A9G / Polycomb protein EED / Polycomb protein SUZ12 / Histone-lysine N-methyltransferase EZH2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 3.901 Å
AuthorsBratkowski, M.A. / Liu, X.
Funding support United States, 6items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM114576 United States
Welch FoundationI-1790 United States
Rita Allen Foundation United States
Cancer Prevention and Research Institute of Texas (CPRIT)R1119 United States
UT Southwestern Endowed Scholar Fund United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)GM121662 United States
CitationJournal: Sci Rep / Year: 2018
Title: An Evolutionarily Conserved Structural Platform for PRC2 Inhibition by a Class of Ezh2 Inhibitors.
Authors: Bratkowski, M. / Yang, X. / Liu, X.
History
DepositionJul 13, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 27, 2018Provider: repository / Type: Initial release
Revision 1.1Apr 24, 2019Group: Author supporting evidence / Data collection / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.2Jan 8, 2020Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 1.3Mar 23, 2022Group: Author supporting evidence / Database references / Derived calculations
Category: database_2 / pdbx_audit_support / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_dist_value / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id
Revision 1.4Oct 4, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Histone-lysine N-methyltransferase EZH2,Polycomb protein SUZ12 (E.C.2.1.1.43) chimera
B: Polycomb protein EED
C: Histone-lysine N-methyltransferase EZH2,Polycomb protein SUZ12 (E.C.2.1.1.43) chimera
D: Polycomb protein EED
hetero molecules


Theoretical massNumber of molelcules
Total (without water)300,59421
Polymers299,0214
Non-polymers1,57317
Water00
1
A: Histone-lysine N-methyltransferase EZH2,Polycomb protein SUZ12 (E.C.2.1.1.43) chimera
B: Polycomb protein EED
hetero molecules


Theoretical massNumber of molelcules
Total (without water)150,56011
Polymers149,5102
Non-polymers1,0509
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area8370 Å2
ΔGint-99 kcal/mol
Surface area38980 Å2
MethodPISA
2
C: Histone-lysine N-methyltransferase EZH2,Polycomb protein SUZ12 (E.C.2.1.1.43) chimera
D: Polycomb protein EED
hetero molecules


Theoretical massNumber of molelcules
Total (without water)150,03410
Polymers149,5102
Non-polymers5238
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5420 Å2
ΔGint-80 kcal/mol
Surface area39680 Å2
MethodPISA
Unit cell
Length a, b, c (Å)243.880, 243.880, 243.699
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number97
Space group name H-MI422

-
Components

#1: Protein Histone-lysine N-methyltransferase EZH2,Polycomb protein SUZ12 (E.C.2.1.1.43) chimera / ENX-1 / Enhancer of zeste homolog 2 / Lysine N-methyltransferase 6


Mass: 99155.523 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EZH2, KMT6, SUZ12, CHET9, JJAZ1, KIAA0160 / Production host: Saccharomyces cerevisiae (brewer's yeast)
References: UniProt: Q15910, UniProt: Q15022, histone-lysine N-methyltransferase
#2: Protein Polycomb protein EED / hEED / Embryonic ectoderm development protein / WD protein associating with integrin cytoplasmic ...hEED / Embryonic ectoderm development protein / WD protein associating with integrin cytoplasmic tails 1 / WAIT-1


Mass: 50354.766 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EED / Production host: Saccharomyces cerevisiae (brewer's yeast) / References: UniProt: O75530
#3: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 16 / Source method: obtained synthetically / Formula: Zn
#4: Chemical ChemComp-A9G / 1-[(2S)-butan-2-yl]-N-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-3-methyl-6-[6-(piperazin-1-yl)pyridin-3-yl]-1H-indole-4-carboxamide


Mass: 526.672 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C31H38N6O2
Sequence detailsTHIS MUTATION INADVERTENTLY OCCURRED DURING CLONING.

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.03 Å3/Da / Density % sol: 59.4 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 7.2 / Details: 200 mM ammonium citrate pH 7.2, 16% PEG 3350

-
Data collection

DiffractionMean temperature: 93 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.979 Å
DetectorType: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Nov 10, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979 Å / Relative weight: 1
ReflectionResolution: 3.9→50 Å / Num. obs: 33621 / % possible obs: 100 % / Redundancy: 26.2 % / CC1/2: 0.932 / Rmerge(I) obs: 0.375 / Rpim(I) all: 0.075 / Net I/σ(I): 14.6
Reflection shellResolution: 3.9→3.97 Å / Redundancy: 26.2 % / Rmerge(I) obs: 4.734 / Mean I/σ(I) obs: 1.17 / Num. unique obs: 1643 / CC1/2: 0.646 / Rpim(I) all: 0.939 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX(1.11.1_2575)refinement
HKL-3000data reduction
HKL-3000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5IJ7

5ij7


Resolution: 3.901→40.647 Å / SU ML: 0.52 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 29.04 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.3 1367 5.1 %
Rwork0.242 --
obs0.245 26797 79.66 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 3.901→40.647 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms13419 0 55 0 13474
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00813821
X-RAY DIFFRACTIONf_angle_d0.75418557
X-RAY DIFFRACTIONf_dihedral_angle_d5.2898310
X-RAY DIFFRACTIONf_chiral_restr0.051965
X-RAY DIFFRACTIONf_plane_restr0.0052392
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
3.9013-4.04070.2984520.2639786X-RAY DIFFRACTION25
4.0407-4.20230.38780.24761192X-RAY DIFFRACTION38
4.2023-4.39330.2689950.2381707X-RAY DIFFRACTION54
4.3933-4.62470.3021350.24272519X-RAY DIFFRACTION80
4.6247-4.91390.28121510.23663125X-RAY DIFFRACTION98
4.9139-5.29260.28452020.24553122X-RAY DIFFRACTION100
5.2926-5.82380.31661720.25323163X-RAY DIFFRACTION100
5.8238-6.66340.34721490.2673216X-RAY DIFFRACTION100
6.6634-8.3830.37331580.24923261X-RAY DIFFRACTION100
8.383-40.64890.24961750.21673339X-RAY DIFFRACTION99
Refinement TLS params.Method: refined / Origin x: -68.3387 Å / Origin y: -22.3818 Å / Origin z: -37.2141 Å
111213212223313233
T0.1831 Å20.0389 Å2-0.4267 Å2-0.2862 Å2-1.0687 Å2---0.4854 Å2
L-0.1169 °20.1145 °20.108 °2-0.0743 °20.1946 °2--0.3604 °2
S0.0824 Å °-0.0931 Å °-0.3512 Å °0.1121 Å °0.1887 Å °-0.4116 Å °0.2265 Å °0.5964 Å °-0.2484 Å °
Refinement TLS groupSelection details: all

+
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