Mechanism of <i>S</i>-Adenosyl-<scp>l</scp>-methionine <i>C</i>-Methylation by Cobalamin-dependent Radical <i>S</i>-Adenosyl-<scp>l</scp>-methionine Methylase in 1-Amino-2-methylcyclopropanecarboxylic Acid Biosynthesis
Fumitaka Kudo, Atsushi Minato, Shusuke Sato, Nayuta Nagano, Chitose Maruyama, Yoshimitsu Hamano, Junko Hashimoto, Ikuko Kozone, Kazuo Shin‐ya, Tadashi Eguchi
Abstract
The radical S-adenosyl-l-methionine (SAM) methylase Orf29 catalyzes the C-methylation of SAM in the biosynthesis of 1-amino-2-methylcyclopropanecarboxylic acid. Here, we determined that the methylation product is (4″R)-4″-methyl-SAM. Furthermore, we found that the 5′-deoxyadenosyl radical generated by Orf29 abstracts the pro-R hydrogen atom from the C-4″ position of SAM to generate the radical intermediate, which reacts with methylcobalamin to give (4″R)-4″-methyl-SAM. Consequently, the Orf29-catalyzed C-methylation was confirmed to proceed with retention of configuration.
Topics & Concepts
ChemistryMethylationMethylcobalaminMethyltransferaseCobalaminMethionineStereochemistryMethyl groupBiosynthesisAmino acidBiochemistryVitamin B12EnzymeOrganic chemistryDNAAlkylMetalloenzymes and iron-sulfur proteinsPorphyrin Metabolism and DisordersRNA modifications and cancer