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

Xiao, B., Jing, C., Wilson, J.R., Walker, P.A., Vasisht, N., Kelly, G., Howell, S., Taylor, I.A., Blackburn, G.M. and Gamblin, S.J. (2003) Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature, 421 (6923). pp. 652-656. ISSN 0028-0836


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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.

Item Type: Article
Copyright, Publisher and Additional Information: © 2003 Nature Publishing Group
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Science (Sheffield) > Department of Chemistry (Sheffield)
The University of Sheffield > University of Sheffield Research Centres and Institutes > The Krebs Institute for Biomolecular Research (Sheffield)
Depositing User: Repository Officer
Date Deposited: 24 Sep 2004
Last Modified: 05 Jun 2014 05:28
Published Version: http://www.nature.com/nature
Status: Published
Refereed: Yes
Identification Number: 10.1038/nature01378
URI: http://eprints.whiterose.ac.uk/id/eprint/111

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