Structure and catalytic mechanism of the human histone methyltransferase SET7/9 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2003-02

AUTHORS

Bing Xiao, Chun Jing, Jonathan R. Wilson, Philip A. Walker, Nishi Vasisht, Geoff Kelly, Steven Howell, Ian A. Taylor, G. Michael Blackburn, Steven J. Gamblin

ABSTRACT

Acetylation, phosphorylation and methylation of the amino-terminal tails of histones are thought to be involved in the regulation of chromatin structure and function. With just one exception, the enzymes identified in the methylation of specific lysine residues on histones (histone methyltransferases) belong to the SET family. The high-resolution crystal structure of a ternary complex of human SET7/9 with a histone peptide and cofactor reveals that the peptide substrate and cofactor bind on opposite surfaces of the enzyme. The target lysine accesses the active site of the enzyme and the S-adenosyl-l-methionine (AdoMet) cofactor by inserting its side chain into a narrow channel that runs through the enzyme, connecting the two surfaces. Here we show from the structure and from solution studies that SET7/9, unlike most other SET proteins, is exclusively a mono-methylase. The structure indicates the molecular basis of the specificity of the enzyme for the histone target, and allows us to propose a model for the methylation reaction that accounts for the role of many of the residues that are invariant across the SET family. More... »

PAGES

652

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature01378

DOI

http://dx.doi.org/10.1038/nature01378

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1043777921

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12540855


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