title: Auxiliary iron-sulfur cofactors in radical SAM enzymes.
abstract: A vast number of enzymes are now known to belong to a superfamily known as radical SAM, which all contain a [4Fe-4S] cluster ligated by three cysteine residues. The remaining, unligated, iron ion of the cluster binds in contact with the α-amino and α-carboxylate groups of S-adenosyl-l-methionine (SAM). This binding mode facilitates inner-sphere electron transfer from the reduced form of the cluster into the sulfur atom of SAM, resulting in a reductive cleavage of SAM to methionine and a 5'-deoxyadenosyl radical. The 5'-deoxyadenosyl radical then abstracts a target substrate hydrogen atom, initiating a wide variety of radical-based transformations. A subset of radical SAM enzymes contains one or more additional iron-sulfur clusters that are required for the reactions they catalyze. However, outside of a subset of sulfur insertion reactions, very little is known about the roles of these additional clusters. This review will highlight the most recent advances in the identification and characterization of radical SAM enzymes that harbor auxiliary iron-sulfur clusters. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, United States.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Lanz
authors.affiliation: Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, United States; Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, United States. Electronic address: squire@psu.edu.
authors.forename: Squire J
authors.initials: SJ
authors.lastname: Booker
mesh_terms: D003067:Coenzymes / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism*; D008780:Methyltransferases / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D017434:Protein Structure, Tertiary; D012436:S-Adenosylmethionine / Q000737:chemistry / Q000378:metabolism*; D013455:Sulfur / Q000378:metabolism
chemical_list: D003067:Coenzymes; D005609:Free Radicals; D007506:Iron-Sulfur Proteins; D013455:Sulfur; D012436:S-Adenosylmethionine; D008780:Methyltransferases
keywords: Cofactor maturation; Iron–sulfur cluster; Radical SAM; Radical-dependent post-translational modification; S-adenosylmethionine; SPASM/twitch domain