Identification and function of auxiliary iron-sulfur clusters in radical SAM enzymes

Nicholas D. Lanz, Squire J. Booker

Research output: Contribution to journalReview articlepeer-review

69 Scopus citations


Radical SAM (RS) enzymes use a 5′-deoxyadenosyl 5′-radical generated from a reductive cleavage of S-adenosyl-l-methionine to catalyze over 40 distinct reaction types. A distinguishing feature of these enzymes is a [4Fe-4S] cluster to which each of three iron ions is ligated by three cysteinyl residues most often located in a Cx3Cx2C motif. The α-amino and α-carboxylate groups of SAM anchor the molecule to the remaining iron ion, which presumably facilitates its reductive cleavage. A subset of RS enzymes contains additional iron-sulfur clusters, - which we term auxiliary clusters - most of which have unidentified functions. Enzymes in this subset are involved in cofactor biosynthesis and maturation, post-transcriptional and post-translational modification, enzyme activation, and antibiotic biosynthesis. The additional clusters in these enzymes have been proposed to function in sulfur donation, electron transfer, and substrate anchoring. This review will highlight evidence supporting the presence of multiple iron-sulfur clusters in these enzymes as well as their predicted roles in catalysis. This article is part of a special issue entitled: Radical SAM enzymes and radical enzymology.

Original languageEnglish (US)
Pages (from-to)1196-1212
Number of pages17
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Issue number11
StatePublished - Nov 2012

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology


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