Emerging themes in radical SAM chemistry

Curr Opin Struct Biol. 2012 Dec;22(6):701-10. doi: 10.1016/j.sbi.2012.10.005. Epub 2012 Nov 8.

Abstract

Enzymes in the radical SAM (RS) superfamily catalyze a wide variety of reactions through unique radical chemistry. The characteristic markers of the superfamily include a [4Fe-4S] cluster coordinated to the protein via a cysteine triad motif, typically CX(3)CX(2)C, with the fourth iron coordinated by S-adenosylmethionine (SAM). The SAM serves as a precursor for a 5'-deoxyadenosyl radical, the central intermediate in nearly all RS enzymes studied to date. The SAM-bound [4Fe-4S] cluster is located within a partial or full triosephosphate isomerase (TIM) barrel where the radical chemistry occurs protected from the surroundings. In addition to the TIM barrel and a RS [4Fe-4S] cluster, many members of the superfamily contain additional domains and/or additional Fe-S clusters. Recently characterized superfamily members are providing new examples of the remarkable range of reactions that can be catalyzed, as well as new structural and mechanistic insights into these fascinating reactions.

Publication types

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

MeSH terms

  • Animals
  • Biocatalysis
  • Free Radicals / chemistry*
  • Free Radicals / metabolism
  • Oxidation-Reduction
  • S-Adenosylmethionine / chemistry*
  • S-Adenosylmethionine / metabolism

Substances

  • Free Radicals
  • S-Adenosylmethionine