Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

Histone methyltransferases (HMTs) transfer a methyl group from the cofactor S-adenosyl methionine to lysine or arginine residues on histone tails, thereby regulating chromatin compaction, binding of effector proteins and gene transcription. HMTs constitute an emerging target class in diverse disease areas, and selective chemical probes are necessary for target validation. Potent and selective competitors of the substrate peptide have been reported, but the chemical tractability of the cofactor binding site is poorly understood. Here, a systematic analysis of this site across structures of 14 human HMTs or close homologues was conducted. The druggability, interaction hotspots, and diversity of the cofactor binding pocket were dissected. This analysis strongly suggests that this site is chemically tractable. General principles underlying tight binding and specific guidelines to achieve selective inhibition are presented.

Citation

Valérie Campagna-Slater, Man Wai Mok, Kong T Nguyen, Miklos Feher, Rafael Najmanovich, Matthieu Schapira. Structural chemistry of the histone methyltransferases cofactor binding site. Journal of chemical information and modeling. 2011 Mar 28;51(3):612-23

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 21366357

View Full Text