RESEARCH ARTICLE


Structural Chemistry of Human SET Domain Protein Methyltransferases



Matthieu Schapira*, 1, 2
1 Structural Genomics Consortium, University of Toronto, MaRS Centre, Toronto, Ontario, M5G 1L7, Canada
2 Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Building, Toronto, Ontario, M5S 1A8, Canada


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© Matthieu Schapira; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Structural Genomics Consortium, University of Toronto, MaRS Centre, Toronto, Ontario, M5G 1L7, Canada; Tel: 416-978-3092; Fax: 416-946-0880; E-mail: matthieu.schapira@utoronto.ca


Abstract

There are about fifty SET domain protein methyltransferases (PMTs) in the human genome, that transfer a methyl group from S-adenosyl-L-methionine (SAM) to substrate lysines on histone tails or other peptides. A number of structures in complex with cofactor, substrate, or inhibitors revealed the mechanisms of substrate recognition, methylation state specificity, and chemical inhibition. Based on these structures, we review the structural chemistry of SET domain PMTs, and propose general concepts towards the development of selective inhibitors.

Keywords: Methyltransferase, SET domain, structure, PMT, histone, epigenetics.