PROSITE documentation PDOC51918Radical SAM core domain profile
The Radical S-adenosylmethionine (SAM) superfamily is an ancient and diverged group found from all three domains of life. Radical SAM proteins share an unusual Fe-S cluster associated with generation of a free radical by reductive cleavage of SAM and often provide an anaerobic or oxygen-independent mechanism that is found as an aerobic reaction in other proteins.They catalyze diverse reactions, including unusual methylations, isomerization, sulfur insertion, ring formation, anaerobic oxidation and protein radical formation. Radical SAM proteins function in DNA precursor, vitamin, cofactor, antibiotic and herbicide biosynthesis and in biodegradation pathways [1].
Radical SAM proteins share several common features, notably three strictly conserved cysteine residues generally included in the CxxxCxxC motif. These critical cysteines coordinate the unusual [4Fe-4S]2+/1+ cluster, while SAM serves as ligand for the fourth iron atom and acts as a cofactor or a cosubstrate [1]. The radical SAM enzymes biochemically characterized to date have in common the cleavage of the [4Fe-4S]1+-SAM complex to [4Fe-4S]2+-Met and the 5'-deoxyadenosyl radical, which abstracts a hydrogen atom from the substrate to initiate a radical mechanism [2,3].
The Radical SAM core domain displays a fold related to the β-barrel or TIM barrel, in which β-strands are arranged in a barrel-like array, with peripheral helices intervening between β-strands (see <PDB:5V1Q>). The [4Fe-4S] clusters and substrates are bound within the barrels, as is typical of TIM barrel enzymes [4,5].
The profile we developed covers the entire Radical SAM core domain.
Last update:March 2020 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Sofia H.J. Chen G. Hetzler B.G. Reyes-Spindola J.F. Miller N.E. |
| Title | Radical SAM, a novel protein superfamily linking unresolved steps in familiar biosynthetic pathways with radical mechanisms: functional characterization using new analysis and information visualization methods. | |
| Source | Nucleic. Acids. Res. 29:1097-1106(2001). | |
| PubMed ID | 11222759 | |
| DOI | 10.1093/nar/29.5.1097 |
| 2 | Authors | Benjdia A. Heil K. Barends T.R.M. Carell T. Schlichting I. |
| Title | Structural insights into recognition and repair of UV-DNA damage by Spore Photoproduct Lyase, a radical SAM enzyme. | |
| Source | Nucleic. Acids. Res. 40:9308-9318(2012). | |
| PubMed ID | 22761404 | |
| DOI | 10.1093/nar/gks603 |
| 3 | Authors | Frey P.A. Hegeman A.D. Ruzicka F.J. |
| Title | The Radical SAM Superfamily. | |
| Source | Crit. Rev. Biochem. Mol. Biol. 43:63-88(2008). | |
| PubMed ID | 18307109 | |
| DOI | 10.1080/10409230701829169 |
| 4 | Authors | Davis K.M. Schramma K.R. Hansen W.A. Bacik J.P. Khare S.D. Seyedsayamdost M.R. Ando N. |
| Title | Structures of the peptide-modifying radical SAM enzyme SuiB elucidate the basis of substrate recognition. | |
| Source | Proc. Natl. Acad. Sci. U. S. A. 114:10420-10425(2017). | |
| PubMed ID | 28893989 | |
| DOI | 10.1073/pnas.1703663114 |
| 5 | Authors | Dowling D.P. Vey J.L. Croft A.K. Drennan C.L. |
| Title | Structural diversity in the AdoMet radical enzyme superfamily. | |
| Source | Biochim. Biophys. Acta. 1824:1178-1195(2012). | |
| PubMed ID | 22579873 | |
| DOI | 10.1016/j.bbapap.2012.04.006 |
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