PDBsum entry: 2rfi

Transferase

PDB id: 2rfi

Contents

Protein chains

261 a.a. *

Ligands

LYS-GLN-THR-ALA-ARG-MLY-SER-THR

THR-ALA-ARG-MLY-SER-THR

SAH ×2

Metals

_ZN ×8

Waters ×686

* Residue conservation analysis

PDB id:

2rfi

Name:

Transferase

Title:

Crystal structure of catalytic domain of human euchromatic histone methyltransferase 1 in complex with sah and dimethylated h3k9 peptide

Structure:

Histone-lysine n-methyltransferase, h3 lysine-9 specific 5. Chain: a, b. Fragment: catalytic domain: residues 951-1235. Synonym: histone h3-k9 methyltransferase 5, h3-k9-hmtase 5, euchromatic histone-lysine n-methyltransferase 1, eu- hmtase1, g9a-like protein 1, glp1. Engineered: yes. Histone h3.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ehmt1, euhmtase1, kiaa1876. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic dimethylated h3k9 peptide

Resolution:

1.59Å R-factor: 0.194 R-free: 0.220

Authors:

J.Min,H.Wu,P.Loppnau,J.Weigelt,M.Sundstrom,C.H.Arrowsmith, A.M.Edwards,A.Bochkarev,A.N.Plotnikov,Structural Genomics Consortium (Sgc)

Key ref:

H.Wu et al. (2010). Structural biology of human H3K9 methyltransferases. Plos One, 5, e8570. PubMed id: 20084102 DOI: 10.1371/journal.pone.0008570

Date:

30-Sep-07 Release date: 23-Oct-07

Protein chains

Q9H9B1  (EHMT1_HUMAN) -  Histone-lysine N-methyltransferase EHMT1

Seq: 1298 a.a.

Struc: 261 a.a.

Enzyme reactions

• Enzyme class: E.C.2.1.1.43 - Histone-lysine N-methyltransferase.
• Reaction: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N₆-methyl-L-lysine-[histone]

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine (Bound ligand (Het Group name = SAH) corresponds exactly) + N(6)-methyl-L-lysine-[histone]

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: nucleus (1 term)
• Biological process: chromatin modification (1 term)
• Biochemical function: zinc ion binding (2 terms)

Added reference

DOI no: 10.1371/journal.pone.0008570

Plos One 5:e8570 (2010)

PubMed id: 20084102

Structural biology of human H3K9 methyltransferases.

H.Wu, J.Min, V.V.Lunin, T.Antoshenko, L.Dombrovski, H.Zeng, A.Allali-Hassani, V.Campagna-Slater, M.Vedadi, C.H.Arrowsmith, A.N.Plotnikov, M.Schapira.

ABSTRACT

SET domain methyltransferases deposit methyl marks on specific histone tail lysine residues and play a major role in epigenetic regulation of gene transcription. We solved the structures of the catalytic domains of GLP, G9a, Suv39H2 and PRDM2, four of the eight known human H3K9 methyltransferases in their apo conformation or in complex with the methyl donating cofactor, and peptide substrates. We analyzed the structural determinants for methylation state specificity, and designed a G9a mutant able to tri-methylate H3K9. We show that the I-SET domain acts as a rigid docking platform, while induced-fit of the Post-SET domain is necessary to achieve a catalytically competent conformation. We also propose a model where long-range electrostatics bring enzyme and histone substrate together, while the presence of an arginine upstream of the target lysine is critical for binding and specificity. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.