西亚试剂：A Radically Different Mechanism for S-Adenosylmethionine-De

A Radically Different Mechanism for S-Adenosylmethionine-Dependent Methyltransferases

T. L. Grove, J. S. Benner, M. I. Radle, J. H. Ahlum, B. J. Landgraf, C. Krebs, S. J. Booker

Abstract

Methylation of small molecules and macromolecules is crucial in metabolism, cell signaling, and epigenetic programming and is most often achieved by S-adenosylmethionine (SAM)–dependent methyltransferases. Most employ an SN2 mechanism to methylate nucleophilic sites on their substrates, but recently, radical SAM enzymes have been identified that methylate carbon atoms that are not inherently nucleophilic via the intermediacy of a 5′-deoxyadenosyl 5′-radical. We have determined the mechanisms of two such reactions targeting the sp2-hybridized carbons at positions 2 and 8 of adenosine 2503 in 23S ribosomal RNA, catalyzed by RlmN and Cfr, respectively. In neither case is a methyl group transferred directly from SAM to the RNA; rather, both reactions proceed by a ping-pong mechanism involving intermediate methylation of a conserved cysteine residue.