Epigenetic Proteins as Emerging Drug Targets

Substrate-Differentiated Transition States of SET7/9-Catalyzed Lysine Methylation

“…[11][12][13][14] Protein lysine methyltransferases (PKMTs) are the posttranslationally-modifying enzymes that catalyze lysine methylation with S-adenosyl-L-methionine (SAM) as a cofactor. 11,[15][16] The methods using experimental binding and kinetic isotope effects (BIE and KIEs) as geometrical constraints coupled with computational modeling allow to uncover atomistic details of the TS structures of PKMT-catalyzed methylation reactions. [17][18] Similar to other homologous enzymes, closely related PKMTs can adopt distinct TS as revealed by a collection of characteristic KIEs.…”