title: A radically different mechanism for S-adenosylmethionine-dependent methyltransferases.
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 S(N)2 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 sp(2)-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.
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Tyler L
authors.initials: TL
authors.lastname: Grove
authors.forename: Jack S
authors.initials: JS
authors.lastname: Benner
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Radle
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Ahlum
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Landgraf
authors.forename: Carsten
authors.initials: C
authors.lastname: Krebs
authors.forename: Squire J
authors.initials: SJ
authors.lastname: Booker
mesh_terms: D000241:Adenosine / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055162:Biocatalysis; D002244:Carbon / Q000737:chemistry; D055598:Chemical Phenomena; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006859:Hydrogen / Q000737:chemistry; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012329:RNA, Bacterial / Q000378:metabolism; D012338:RNA, Ribosomal, 23S / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000201:enzymology
chemical_list: D001426:Bacterial Proteins; C539943:CFR protein, Staphylococcus aureus; D029968:Escherichia coli Proteins; D012329:RNA, Bacterial; D012338:RNA, Ribosomal, 23S; D002244:Carbon; D012436:S-Adenosylmethionine; D006859:Hydrogen; D008780:Methyltransferases; C558134:RlmN protein, E coli; D000241:Adenosine; D003545:Cysteine