cd01335

Radical_SAM

CDD entry
Member databaseCDD
CDD typedomain
Short nameRadical_SAM
SetRadical_SAM

Description

Radical SAM superfamily. Enzymes of this family generate radicals by combining a 4Fe-4S cluster and S-adenosylmethionine (SAM) in close proximity. They are characterized by a conserved CxxxCxxC motif, which coordinates the conserved iron-sulfur cluster. Mechanistically, they share the transfer of a single electron from the iron-sulfur cluster to SAM, which leads to its reductive cleavage to methionine and a 5'-deoxyadenosyl radical, which, in turn, abstracts a hydrogen from the appropriately positioned carbon atom. Depending on the enzyme, SAM is consumed during this process or it is restored and reused. Radical SAM enzymes catalyze steps in metabolism, DNA repair, the biosynthesis of vitamins and coenzymes, and the biosynthesis of many antibiotics. Examples are biotin synthase (BioB), lipoyl synthase (LipA), pyruvate formate-lyase (PFL), coproporphyrinogen oxidase (HemN), lysine 2,3-aminomutase (LAM), anaerobic ribonucleotide reductase (ARR), and MoaA, an enzyme of the biosynthesis of molybdopterin.
[3, 7, 6, 4, 1, 2, 5]

References

1.S-Adenosyl-L-methionine: beyond the universal methyl group donor. Roje S. Phytochemistry 67, 1686-98, (2006). PMID: 16766004

2.S-adenosylmethionine radical enzymes. Marsh EN, Patwardhan A, Huhta MS. Bioorg Chem 32, 326-40, (2004). PMID: 15381399

3.The Radical SAM Superfamily. Frey PA, Hegeman AD, Ruzicka FJ. Crit Rev Biochem Mol Biol 43, 63-88, (2008). PMID: 18307109

4.S-adenosylmethionine as an oxidant: the radical SAM superfamily. Wang SC, Frey PA. Trends Biochem Sci 32, 101-10, (2007). PMID: 17291766

5.Structure and function of radical SAM enzymes. Layer G, Heinz DW, Jahn D, Schubert WD. Curr Opin Chem Biol 8, 468-76, (2004). PMID: 15450488

6.Iron-sulfur proteins as initiators of radical chemistry. Marquet A, Bui BT, Smith AG, Warren MJ. Nat Prod Rep 24, 1027-40, (2007). PMID: 17898896

7.Self-sacrifice in radical S-adenosylmethionine proteins. Booker SJ, Cicchillo RM, Grove TL. Curr Opin Chem Biol 11, 543-52, (2007). PMID: 17936058

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