[English] 日本語
Yorodumi
- PDB-7t7m: Structure of human GLP SET-domain (EHMT1) in complex with covalen... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7t7m
TitleStructure of human GLP SET-domain (EHMT1) in complex with covalent inhibitor (Compound 1)
ComponentsHistone-lysine N-methyltransferase EHMT1
KeywordsTRANSFERASE/INHIBITOR / GLP / Covalent inhibitor / GENE REGULATION / TRANSFERASE-INHIBITOR complex
Function / homology
Function and homology information


[histone H3]-lysine9 N-methyltransferase / peptidyl-lysine monomethylation / histone H3K9 methyltransferase activity / histone H3K9me2 methyltransferase activity / peptidyl-lysine dimethylation / histone H3K27 methyltransferase activity / protein-lysine N-methyltransferase activity / C2H2 zinc finger domain binding / DNA methylation-dependent heterochromatin formation / Transcriptional Regulation by E2F6 ...[histone H3]-lysine9 N-methyltransferase / peptidyl-lysine monomethylation / histone H3K9 methyltransferase activity / histone H3K9me2 methyltransferase activity / peptidyl-lysine dimethylation / histone H3K27 methyltransferase activity / protein-lysine N-methyltransferase activity / C2H2 zinc finger domain binding / DNA methylation-dependent heterochromatin formation / Transcriptional Regulation by E2F6 / regulation of embryonic development / Transcriptional Regulation by VENTX / response to fungicide / Transferases; Transferring one-carbon groups; Methyltransferases / transcription corepressor binding / methyltransferase activity / Regulation of TP53 Activity through Methylation / PKMTs methylate histone lysines / p53 binding / chromatin organization / positive regulation of cold-induced thermogenesis / Senescence-Associated Secretory Phenotype (SASP) / nuclear body / negative regulation of DNA-templated transcription / chromatin / negative regulation of transcription by RNA polymerase II / zinc ion binding / nucleoplasm / nucleus
Similarity search - Function
Histone-lysine N-methyltransferase EHMT1 / 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 / Ankyrin repeats (many copies) / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain ...Histone-lysine N-methyltransferase EHMT1 / 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 / Ankyrin repeats (many copies) / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain / SET domain superfamily / SET domain / SET domain profile. / SET domain / 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 / Histone-lysine N-methyltransferase EHMT1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.85 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Histone-lysine N-methyltransferase EHMT1
B: Histone-lysine N-methyltransferase EHMT1
C: Histone-lysine N-methyltransferase EHMT1
D: Histone-lysine N-methyltransferase EHMT1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)134,93324
Polymers131,8974
Non-polymers3,03520
Water82946
1
A: Histone-lysine N-methyltransferase EHMT1
D: Histone-lysine N-methyltransferase EHMT1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,46712
Polymers65,9492
Non-polymers1,51910
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2070 Å2
ΔGint-11 kcal/mol
Surface area25060 Å2
MethodPISA
2
B: Histone-lysine N-methyltransferase EHMT1
hetero molecules

C: Histone-lysine N-methyltransferase EHMT1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,46512
Polymers65,9492
Non-polymers1,51710
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation3_555-x,y+1/2,-z+1/21
Buried area2080 Å2
ΔGint-10 kcal/mol
Surface area24880 Å2
MethodPISA
Unit cell
Length a, b, c (Å)95.490, 128.730, 132.500
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein
Histone-lysine N-methyltransferase EHMT1 / Euchromatic histone-lysine N-methyltransferase 1 / Eu-HMTase1 / G9a-like protein 1 / GLP1 / Histone ...Euchromatic histone-lysine N-methyltransferase 1 / Eu-HMTase1 / G9a-like protein 1 / GLP1 / Histone H3-K9 methyltransferase 5 / H3-K9-HMTase 5 / Lysine N-methyltransferase 1D


Mass: 32974.344 Da / Num. of mol.: 4 / Fragment: residues 982-1266
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EHMT1, EUHMTASE1, GLP, KIAA1876, KMT1D / Production host: Escherichia coli (E. coli)
References: UniProt: Q9H9B1, Transferases; Transferring one-carbon groups; Methyltransferases, histone-lysine N-methyltransferase
#2: Chemical
ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 16 / Source method: obtained synthetically / Formula: Zn
#3: 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.: 3 / Source method: obtained synthetically / Formula: C27H40N6O3 / Feature type: SUBJECT OF INVESTIGATION
#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.: 1 / Source method: obtained synthetically / Formula: C27H42N6O3 / Feature type: SUBJECT OF INVESTIGATION
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 46 / 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: 2.92 Å3/Da / Density % sol: 57.87 %
Crystal growTemperature: 290.15 K / Method: vapor diffusion, sitting drop
Details: 0.2 Magnesium Formate, 15% w/v Polyethylene glycol 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.9792 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: 0.9792 Å / Relative weight: 1
ReflectionResolution: 2.85→92.33 Å / Num. obs: 38903 / % possible obs: 100 % / Redundancy: 7.9 % / Biso Wilson estimate: 47.39 Å2 / Rsym value: 0.185 / Net I/σ(I): 11.4
Reflection shellResolution: 2.85→3 Å / Redundancy: 8 % / Rmerge(I) obs: 0.95 / Mean I/σ(I) obs: 0.7 / Num. unique obs: 38841 / Rsym value: 0.95 / % possible all: 100

-
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: 5TUZ

5tuz


Resolution: 2.85→76.69 Å / SU ML: 0.39 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 25.84 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.244 2008 5.17 %
Rwork0.199 36823 -
obs0.201 38831 100 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 119.04 Å2 / Biso mean: 50.8 Å2 / Biso min: 12.65 Å2
Refinement stepCycle: final / Resolution: 2.85→76.69 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8405 0 160 46 8611
Biso mean--59.82 35.23 -
Num. residues----1041
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / % reflection obs: 100 %

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork
2.85-2.92130.3671380.28542604
2.9213-3.00030.30741340.25832577
3.0003-3.08860.37361450.25732602
3.0886-3.18820.32631310.25282612
3.1882-3.30220.28821350.24222601
3.3022-3.43440.29061440.23382591
3.4344-3.59070.27841430.2172610
3.5907-3.780.25121430.2052619
3.78-4.01680.27861280.18762636
4.0168-4.3270.21451590.1722611
4.327-4.76230.18341410.15652636
4.7623-5.45130.18931630.1632635
5.4513-6.86740.24171500.18132681
6.8674-76.690.18351540.17812808

+
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://pdbjlc1.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