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PMID: 12372305 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Structure of the Neurospora SET domain protein DIM-5, a histone H3 lysine methyltransferase.

Cell ·Vol. 111 ·No. 1 ·2002-10-04 ·Pages 117-27

Zhang X, Tamaru H, Khan SI, Horton JR, Keefe LJ, Selker EU, Cheng X

Abstract

AdoMet-dependent methylation of histones is part of the "histone code" that can profoundly influence gene expression. We describe the crystal structure of Neurospora DIM-5, a histone H3 lysine 9 methyltranferase (HKMT), determined at 1.98 A resolution, as well as results of biochemical characterization and site-directed mutagenesis of key residues. This SET domain protein bears no structural similarity to previously characterized AdoMet-dependent methyltransferases but includes notable features such as a triangular Zn3Cys9 zinc cluster in the pre-SET domain and a AdoMet binding site in the SET domain essential for methyl transfer. The structure suggests a mechanism for the methylation reaction and provides the structural basis for functional characterization of the HKMT family and the SET domain.

MeSH Terms
Amino Acid Sequence Binding Sites DNA-Binding Proteins/chemistry Dose-Response Relationship, Drug Drosophila Proteins/chemistry Histone Methyltransferases Histone-Lysine N-Methyltransferase Histones/metabolism Hydrogen-Ion Concentration Methyltransferases/chemistry,metabolism Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Neurospora/enzymology Nuclear Proteins/chemistry Polycomb Repressive Complex 2 Protein Binding Protein Methyltransferases Protein Structure, Tertiary Recombinant Proteins/chemistry Repressor Proteins/chemistry Sequence Homology, Amino Acid Temperature Transcription Factors Ultraviolet Rays X-Ray Diffraction Zinc/chemistry
Chemicals
DNA-Binding Proteins Drosophila Proteins Histones Nuclear Proteins Recombinant Proteins Repressor Proteins Transcription Factors Trl protein, Drosophila Histone Methyltransferases Methyltransferases Protein Methyltransferases E(z) protein, Drosophila Histone-Lysine N-Methyltransferase Polycomb Repressive Complex 2 Zinc
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Zhang Xing
Department of Biochemistry, School of Medicine, Emory University, 1510 Clifton Road, Atlanta, GA 30322, USA.
Tamaru Hisashi
Khan Seema I
Horton John R
Keefe Lisa J
Selker Eric U
Cheng Xiaodong
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/s0092-8674(02)00999-6
Published
2002-10-04
Pages
117-27
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2713760
Subset
IM
Grants
NIGMS NIH HHS · R01 GM061355-03 · United States
NIGMS NIH HHS · GM61355 · United States
NIGMS NIH HHS · R37 GM035690 · United States
NIGMS NIH HHS · R01 GM035690 · United States
NIGMS NIH HHS · GM49245 · United States
NIGMS NIH HHS · GM35690 · United States
NIGMS NIH HHS · R01 GM049245 · United States
NIGMS NIH HHS · R01 GM061355 · United States
External Links
PubMed source DOI: 10.1016/s0092-8674(02)00999-6 PMC Full Text View journal details
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