Radical SAM enzymes in methylation and methylthiolation
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Updated: May 18, 2026

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
Rachel U Hutcheson1, Joan B Broderick
1Department of Chemistry and Biochemistry and the Astrobiology Biogeocatalysis Research Center, Montana State University, Bozeman, MT 59717, USA.
Abstract:
Radical S-adenosyl-l-methionine (SAM) enzymes are a large and diverse superfamily with functions ranging from enzyme activation through a single H atom abstraction to complex organic and metal cofactor synthesis involving a series of steps. Though these enzymes carry out a variety of functions, they share common structural and mechanistic characteristics. All of them contain a site-differentiated [4Fe-4S] cluster, ligated by a CX(3)CX(2)C or similar motif, which binds SAM at the unique iron. The [4Fe-4S](1+) state of the cluster reductively cleaves SAM to produce a 5'-deoxyadenosyl radical, which serves to initiate the diverse reactions catalyzed by these enzymes. Recent highlights in the understanding of radical SAM enzymes will be presented, with a particular emphasis on enzymes catalyzing methylation and methythiolation reactions.
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