[English] 日本語
Yorodumi
- PDB-7t7l: Structure of human G9a SET-domain (EHMT2) in complex with covalen... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7t7l
TitleStructure of human G9a SET-domain (EHMT2) in complex with covalent inhibitor (Compound 1)
ComponentsHistone-lysine N-methyltransferase EHMT2
KeywordsGENE REGULATION / G9a / Covalent inhibitor
Function / homology
Function and homology information


regulation of protein modification process / histone H3K56 methyltransferase activity / : / phenotypic switching / neuron fate specification / : / [histone H3]-lysine9 N-methyltransferase / histone H3K27 methyltransferase activity / histone H3K9 methyltransferase activity / histone H3K9me2 methyltransferase activity ...regulation of protein modification process / histone H3K56 methyltransferase activity / : / phenotypic switching / neuron fate specification / : / [histone H3]-lysine9 N-methyltransferase / histone H3K27 methyltransferase activity / histone H3K9 methyltransferase activity / histone H3K9me2 methyltransferase activity / peptidyl-lysine dimethylation / synaptonemal complex assembly / negative regulation of autophagosome assembly / oocyte development / protein-lysine N-methyltransferase activity / C2H2 zinc finger domain binding / fertilization / : / cellular response to cocaine / : / organ growth / Transcriptional Regulation by E2F6 / spermatid development / behavioral response to cocaine / regulation of DNA replication / RNA Polymerase I Transcription Initiation / Transcriptional Regulation by VENTX / long-term memory / response to fungicide / Transferases; Transferring one-carbon groups; Methyltransferases / cellular response to starvation / transcription corepressor binding / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / promoter-specific chromatin binding / RNA polymerase II transcription regulatory region sequence-specific DNA binding / Regulation of TP53 Activity through Methylation / PKMTs methylate histone lysines / cellular response to xenobiotic stimulus / p53 binding / Senescence-Associated Secretory Phenotype (SASP) / response to ethanol / nuclear speck / chromatin / negative regulation of transcription by RNA polymerase II / zinc ion binding / nucleoplasm / nucleus
Similarity search - Function
Histone-lysine N-methyltransferase EHMT2 / Histone-lysine N-methyltransferase EHMT1/EHMT2 / : / Histone-lysine N-methyltransferase EHMT1/EHMT2, Cys-rich region / Pre-SET domain / Pre-SET motif / Pre-SET domain profile. / N-terminal to some SET domains / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain / SET domain superfamily ...Histone-lysine N-methyltransferase EHMT2 / Histone-lysine N-methyltransferase EHMT1/EHMT2 / : / Histone-lysine N-methyltransferase EHMT1/EHMT2, Cys-rich region / Pre-SET domain / Pre-SET motif / Pre-SET domain profile. / N-terminal to some SET domains / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain / SET domain superfamily / SET domain / SET domain profile. / SET domain / Ankyrin repeat / Ankyrin repeats (3 copies) / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily
Similarity search - Domain/homology
Chem-G4R / Chem-G5U / S-ADENOSYLMETHIONINE / Histone-lysine N-methyltransferase EHMT2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å
AuthorsPark, K.-S. / Kumar, P.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01HD088626 United States
CitationJournal: J.Med.Chem. / Year: 2022
Title: Discovery of the First-in-Class G9a/GLP Covalent Inhibitors.
Authors: Park, K.S. / Xiong, Y. / Yim, H. / Velez, J. / Babault, N. / Kumar, P. / Liu, J. / Jin, J.
History
DepositionDec 15, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 6, 2022Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Aug 24, 2022Group: 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 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.4Mar 13, 2024Group: Source and taxonomy / Category: entity_src_gen

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Histone-lysine N-methyltransferase EHMT2
B: Histone-lysine N-methyltransferase EHMT2
C: Histone-lysine N-methyltransferase EHMT2
D: Histone-lysine N-methyltransferase EHMT2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)135,05328
Polymers130,4204
Non-polymers4,63324
Water6,215345
1
A: Histone-lysine N-methyltransferase EHMT2
C: Histone-lysine N-methyltransferase EHMT2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,52514
Polymers65,2102
Non-polymers2,31512
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2230 Å2
ΔGint-10 kcal/mol
Surface area25000 Å2
MethodPISA
2
B: Histone-lysine N-methyltransferase EHMT2
D: Histone-lysine N-methyltransferase EHMT2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,52714
Polymers65,2102
Non-polymers2,31712
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2220 Å2
ΔGint-11 kcal/mol
Surface area25570 Å2
MethodPISA
Unit cell
Length a, b, c (Å)56.821, 72.303, 85.029
Angle α, β, γ (deg.)71.150, 86.170, 89.100
Int Tables number1
Space group name H-MP1

-
Components

-
Protein , 1 types, 4 molecules ABCD

#1: Protein
Histone-lysine N-methyltransferase EHMT2 / Euchromatic histone-lysine N-methyltransferase 2 / HLA-B-associated transcript 8 / Histone H3-K9 ...Euchromatic histone-lysine N-methyltransferase 2 / HLA-B-associated transcript 8 / Histone H3-K9 methyltransferase 3 / H3-K9-HMTase 3 / Lysine N-methyltransferase 1C / Protein G9a


Mass: 32604.924 Da / Num. of mol.: 4 / Fragment: residues 913-1193
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EHMT2, BAT8, C6orf30, G9A, KMT1C, NG36 / Production host: Escherichia coli (E. coli)
References: UniProt: Q96KQ7, Transferases; Transferring one-carbon groups; Methyltransferases, histone-lysine N-methyltransferase

-
Non-polymers , 5 types, 369 molecules

#2: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 16 / Source method: obtained synthetically / Formula: Zn
#3: Chemical
ChemComp-SAM / S-ADENOSYLMETHIONINE / S-Adenosyl methionine


Mass: 398.437 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C15H22N6O5S
#4: Chemical ChemComp-G5U / N-(6-methoxy-4-{[1-(propan-2-yl)piperidin-4-yl]amino}-7-[3-(pyrrolidin-1-yl)propoxy]quinazolin-2-yl)propanamide


Mass: 498.661 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Formula: C27H42N6O3 / Feature type: SUBJECT OF INVESTIGATION
#5: Chemical ChemComp-G4R / N-(6-methoxy-4-{[1-(propan-2-yl)piperidin-4-yl]amino}-7-[3-(pyrrolidin-1-yl)propoxy]quinazolin-2-yl)prop-2-enamide


Mass: 496.645 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C27H40N6O3 / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 345 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.54 Å3/Da / Density % sol: 51.5 %
Crystal growTemperature: 290.15 K / Method: vapor diffusion, sitting drop
Details: 2% v/v 1,4-Dioxane, 10% w/v Polyethylene glycol 20,000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.97918 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 7, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97918 Å / Relative weight: 1
ReflectionResolution: 1.959→80.299 Å / Num. all: 63720 / Num. obs: 63720 / % possible obs: 98.2 % / Redundancy: 2.4 % / Biso Wilson estimate: 31 Å2 / Rpim(I) all: 0.058 / Rrim(I) all: 0.089 / Rsym value: 0.067 / Net I/av σ(I): 8.3 / Net I/σ(I): 8.9 / Num. measured all: 152076
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique obsRpim(I) allRrim(I) allRsym valueNet I/σ(I) obs% possible all
2.2-2.322.40.4161.82221292130.3550.550.4162.497.4
2.32-2.462.40.2992.62115087730.2550.3950.2993.297.6
2.46-2.632.40.2033.81991582670.1740.2690.2034.297.9
2.63-2.842.40.1256.11851977300.1080.1660.125698.2
2.84-3.112.40.0818.81691370770.070.1080.0818.598.4
3.11-3.482.40.05112.81523664050.0440.0670.05112.698.7
3.48-4.022.30.0414.31344957290.0350.0540.0416.398.9
4.02-4.922.30.0412.71113647830.0360.0550.0418.999
4.92-6.962.40.03813.9878337330.0330.050.03818.899.1
6.96-68.4252.40.03814.3476320100.0330.0510.03820.297.9

-
Processing

Software
NameVersionClassification
PHENIX1.13_2998refinement
SCALA3.3.22data scaling
PDB_EXTRACT3.27data extraction
MOLREPphasing
MOSFLMdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5TTF

5ttf


Resolution: 2.2→68.425 Å / SU ML: 0.27 / Cross valid method: THROUGHOUT / σ(F): 1.96 / Phase error: 30.95 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2507 3096 4.86 %
Rwork0.2043 60551 -
obs0.2065 63647 98.08 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 95.72 Å2 / Biso mean: 44.2625 Å2 / Biso min: 21.76 Å2
Refinement stepCycle: final / Resolution: 2.2→68.425 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8565 0 267 345 9177
Biso mean--46 39.9 -
Num. residues----1065
LS refinement shell

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

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.2-2.23440.34471520.3094270897
2.2344-2.2710.39471390.2923274697
2.271-2.31020.33241420.287271898
2.3102-2.35220.33511420.283273297
2.3522-2.39750.34031540.27271798
2.3975-2.44640.33881460.261272497
2.4464-2.49960.3071260.2474279598
2.4996-2.55770.3291420.2524267398
2.5577-2.62170.2861510.236274798
2.6217-2.69260.24511410.2382277398
2.6926-2.77180.32441290.2393276398
2.7718-2.86130.33381390.2247277698
2.8613-2.96360.22951100.2227276598
2.9636-3.08220.28281530.2206276499
3.0822-3.22250.26841360.2148274199
3.2225-3.39240.2231520.2133279499
3.3924-3.60490.2351320.2042275699
3.6049-3.88320.23521510.1839276199
3.8832-4.2740.20661400.1645278999
4.274-4.89230.20751380.1527278799
4.8923-6.16310.18451570.1574277299

+
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