Current Chemical Genomics and Translational Medicine
2011, 5 : 85-94Published online 2011 August 22. DOI: 10.2174/1875397301005010085
Publisher ID: CCGTM-5-85
RESEARCH ARTICLE
Structural Chemistry of Human SET Domain Protein Methyltransferases
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
* 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
2 Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Building, Toronto, Ontario, M5S 1A8, Canada
* 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.