A radically different mechanism for S-adenosylmethionine-dependent methyltransferases

Science. 2011 Apr 29;332(6029):604-7. doi: 10.1126/science.1200877. Epub 2011 Mar 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / chemistry
  • Adenosine / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Biocatalysis
  • Carbon / chemistry
  • Chemical Phenomena
  • Cysteine / chemistry
  • Cysteine / metabolism
  • Escherichia coli / enzymology
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Hydrogen / chemistry
  • Methylation
  • Methyltransferases / chemistry
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • RNA, Bacterial / metabolism
  • RNA, Ribosomal, 23S / metabolism*
  • S-Adenosylmethionine / metabolism*
  • Staphylococcus aureus / enzymology

Substances

  • Bacterial Proteins
  • CFR protein, Staphylococcus aureus
  • Escherichia coli Proteins
  • RNA, Bacterial
  • RNA, Ribosomal, 23S
  • Carbon
  • S-Adenosylmethionine
  • Hydrogen
  • Methyltransferases
  • RlmN protein, E coli
  • Adenosine
  • Cysteine