title: Structural biology and chemistry of protein arginine methyltransferases.
abstract: Protein arginine methyltransferases (PRMTs), an emerging target class in drug discovery, can methylate histones and other substrates, and can be divided into three subgroups, based on the methylation pattern of the reaction product (monomethylation, symmetrical or asymmetrical dimethylation). Here, we review the growing body of structural information characterizing this protein family, including structures in complex with substrate-competitive and allosteric inhibitors. We outline structural differences between type I, II and III enzymes and propose a model underlying class-specificity. We analyze the structural plasticity and diversity of the substrate, cofactor and allosteric binding sites, and propose that the conformational dynamics of PRMTs can be exploited towards the discovery of allosteric inhibitors that would antagonize conformationally active states.
authors.affiliation: Structural Genomics Consortium , University of Toronto , Toronto , ON M5G 1L7 , Canada . Email: matthieu.schapira@utoronto.ca ; Tel: +1-416-978-3092 ; The Department of Pharmacology and Toxicology , University of Toronto , Toronto , ON M5S 1A8 , Canada.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Schapira
authors.affiliation: Structural Genomics Consortium , University of Toronto , Toronto , ON M5G 1L7 , Canada . Email: matthieu.schapira@utoronto.ca ; Tel: +1-416-978-3092.
authors.forename: Renato
authors.initials: R
authors.lastname: Ferreira de Freitas