The Burden Borne by Protein Methyltransferases: Rates and Equilibria of Nonenzymatic Methylation of Amino Acid Side-Chains by SAM in Water

Abstract

SAM is a powerful methylating agent, with a methyl group transfer potential matching the phosphoryl group transfer potential of ATP. SAM-dependent N-methyltransferases have evolved to catalyze the modification of specific lysine residues in histones and transcription factors, in addition to generating epinephrine, N-methylnicotinamide, and a quaternary amine (betaine) that is used to maintain osmotic pressure in plants and halophilic bacteria. To assess the catalytic power of these enzymes and their potential susceptibility to transition state and multisubstrate analogue inhibitors, we determined the rates and positions of equilibrium of methyl transfer from the trimethylsulfonium ion to model amines in the absence of a catalyst.