Radical SAM

Radical_SAM
Identifiers
Symbol Radical_SAM
Pfam PF04055
InterPro IPR007197
SCOP 102114
SUPERFAMILY 102114

Radical SAM is a designation for a superfamily of enzymes that use a [4Fe-4S]+ cluster to reductively cleave S-adenosyl-L-methionine (SAM) to generate a radical, usually a 5′-deoxyadenosyl radical, as a critical intermediate.[1] These enzymes utilize this potent radical intermediate to perform an array of unusual and chemically difficult transformations, often to functionalize unactivated C-H bonds. Examples of radical SAM enzymes include various enzymes involved in cofactor biosynthesis, enzyme activation, peptide modification, post-transcriptional and post-translational modifications, metalloprotein cluster formation, tRNA modification, lipid metabolism, biosynthesis of antibiotics and natural products etc. The vast majority of known radical SAM enzymes belong to the radical SAM superfamily,[2][3] and have a cysteine-rich motif that matches or resembles CxxxCxxC.

Examples of radical SAM enzymes found within the radical SAM superfamily include:

In addition, several non-canonical radical SAM enzymes have been described. These cannot be recognized by the Pfam hidden Markov model PF04055, but still use three Cys residues as ligands to a 4Fe4S cluster and produce a radical from S-adenosylmethionine. These include

  1. ↑ Booker, SJ; Grove, TL (2010). "Mechanistic and functional versatility of radical SAM enzymes". F1000 biology reports. 2: 52. doi:10.3410/B2-52. PMC 2996862Freely accessible. PMID 21152342.
  2. ↑ Sofia, HJ; Chen, G; Hetzler, BG; Reyes-Spindola, JF; Miller, NE (2001). "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". Nucleic Acids Research. 29 (5): 1097–106. doi:10.1093/nar/29.5.1097. PMC 29726Freely accessible. PMID 11222759.
  3. ↑ Frey, PA; Hegeman, AD; Ruzicka, FJ (2008). "The Radical SAM Superfamily". Critical reviews in biochemistry and molecular biology. 43 (1): 63–88. doi:10.1080/10409230701829169. PMID 18307109.
  4. ↑ Zhang, Q; Li, Y; Chen, D; Yu, Y; Duan, L; Shen, B; Liu, W (2011). "Radical-mediated enzymatic carbon chain fragmentation-recombination". Nature Chemical Biology. 7 (3): 154–60. doi:10.1038/nchembio.512. PMC 3079562Freely accessible. PMID 21240261.
  5. ↑ Bruender, NA; Wilcoxen, J; Britt, RD; Bandarian, V (2016). "Biochemical and Spectroscopic Characterization of a Radical S‐Adenosyl‐L‐methionine Enzyme Involved in the Formation of a Peptide Thioether Cross-Link". Biochemistry. 55: 2122–34. doi:10.1021/acs.biochem.6b00145. PMID 27007615.
  6. ↑ Chatterjee, A; Li, Y; Zhang, Y; Grove, TL; Lee, M; Krebs, C; Booker, SJ; Begley, TP; Ealick, SE (2008). "Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily". Nature Chemical Biology. 4 (12): 758–65. doi:10.1038/nchembio.121. PMC 2587053Freely accessible. PMID 18953358.
  7. ↑ Zhang, Y; Zhu, X; Torelli, AT; Lee, M; Dzikovski, B; Koralewski, RM; Wang, E; Freed, J; et al. (2010). "Diphthamide biosynthesis requires an organic radical generated by an iron-sulphur enzyme". Nature. 465 (7300): 891–6. doi:10.1038/nature09138. PMC 3006227Freely accessible. PMID 20559380.
  8. ↑ Kamat, SS; Williams, HJ; Raushel, FM (2011). "Intermediates in the transformation of phosphonates to phosphate by bacteria". Nature. 480 (7378): 570–3. doi:10.1038/nature10622. PMC 3245791Freely accessible. PMID 22089136.
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