Radical SAM
| Radical_SAM | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Radical_SAM | ||||||||
| Pfam | PF04055 | ||||||||
| InterPro | IPR007197 | ||||||||
| SCOP | 102114 | ||||||||
| SUPERFAMILY | 102114 | ||||||||
| |||||||||
Radical SAM is a designation for group of enzymatic reactions sharing the property that an iron-sulfur cluster in the enzyme cleaves S-Adenosyl methionine (SAM) reductively to produce a radical, usually a 5′-deoxyadenosyl radical, as a critical intermediate.[1] The radical intermediate allows enzymes to perform a wide variety of unusual chemical transformations. Examples of radical SAM enzymes include various enzymes of cofactor biosynthesis, enzyme activation, peptide modification, metalloprotein cluster formation, tRNA modification, lipid metabolism, 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:
- AblA - lysine 2,3-aminomutase (osmolyte biosynthesis - N-epsilon-acetyl-beta-lysine)
- AlbA - subtilosin maturase (peptide modification)
- AtsB - anaerobic sulfatase activase (enzyme activation)
- BchE - anaerobic magnesium protoporphyrin-IX oxidative cyclase (cofactor biosynthesis - chlorophyll)
- BioB - biotin synthase (cofactor biosynthesis - biotin)
- BlsE - cytosylglucuronic acid decarboxylase - blasticidin S biosynthesis
- BtrN - butirosin biosynthesis pathway oxidoreductase (aminoglycoside antibiotic biosynthesis)
- CofG - FO synthase, CofG subunit (cofactor biosynthesis - F420)
- CofH - FO synthase, CofH subunit (cofactor biosynthesis - F420)
- CutD - trimethylamine lyase-activating enzyme
- DesII - D-desosamine biosynthesis deaminase (sugar modification for macrolide antibiotic biosynthesis)
- EpmB - elongation factor P beta-lysylation protein (protein modification)
- HemN - oxygen-independent coproporphyrinogen III oxidase (cofactor biosynthesis - heme)
- HmdB - 5,10-methenyltetrahydromethanopterin hydrogenase cofactor biosynthesis protein HmdB (note unusual CX5CX2C motif)
- HpnR - hopanoid C-3 methylase (lipid biosynthesis - 3-methylhopanoid production)
- HydE - [FeFe] hydrogenase H-cluster radical SAM maturase (metallocluster assembly)
- HydG - [FeFe] hydrogenase H-cluster radical SAM maturase (metallocluster assembly)
- LipA - lipoyl synthase (cofactor biosynthesis - lipoyl)
- MftC - mycofactocin system maturase (peptide modification/cofactor biosynthesis - predicted)
- MiaB - tRNA methylthiotransferase (tRNA modification)
- MoaA - Mo cofactor biosynthesis protein A (cofactor biosynthesis - molybdenum cofactor)
- MqnC - dehypoxanthine futalosine cyclase (cofactor biosynthesis - menaquinone via futalosine)
- NifB - cofactor biosynthesis protein nifB (cofactor biosynthesis - FeMo cofactor)
- NirJ - heme d1 biosynthesis radical SAM protein NirJ (cofactor biosynthesis - heme d1)
- NosL - complex rearrangement of tryptophan to 3-methyl-2-indolic acid - nosiheptide biosynthesis [4]
- NrdG - anaerobic ribonucleoside-triphosphate reductase activase (enzyme activation)
- PeaB - quinohemoprotein amine dehydrogenase maturation protein (enzyme activation)
- PflA - pyruvate formate-lyase activating enzyme (enzyme activation)
- PqqE - PQQ biosynthesis enzyme (peptide modification / cofactor biosynthesis - PQQ)
- PylB - pyrrolysine biosynthesis protein PylB (amino acid biosynthesis - pyrrolysine)
- QueE - 7-carboxy-7-deazaguanine (CDG) synthase
- RimO - ribosomal protein S12 methylthiotransferase
- RlmN - 23S rRNA m2A2503 methyltransferase (rRNA modification)
- ScfB - SCIFF maturase (peptide modification - predicted)
- SkfB - sporulation killing factor maturase
- SplB - spore photoproduct lyase (DNA repair)
- ThiH - thiazole biosynthesis protein ThiH (cofactor biosynthesis - thiamine)
- TsrT - tryptophan 2-C-methyltransferase (amino acid modification - antibiotic biosynthesis)
- TYW1 - 4-demethylwyosine synthase (tRNA modification)
- YqeV - tRNA methylthiotransferase (tRNA modification)
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
- ThiC (PF01964) - thiamine biosynthesis protein ThiC (cofactor biosynthesis - thiamine) (Cys residues near extreme C-terminus) [5]
- Dph2 (PF01866) - diphthamide biosynthesis enzyme Dph2 (protein modification - diphthamide in translation elongation factor 2) (note different radical production, a 3-amino-3-carboxypropyl radical) [6]
- PhnJ (PF06007) - phosphonate metabolism protein PhnJ (C-P phosphonate bond cleavage) [7]
- ↑ Booker, SJ; Grove, TL (2010). "Mechanistic and functional versatility of radical SAM enzymes". F1000 biology reports 2: 52. doi:10.3410/B2-52. PMC 2996862. PMID 21152342.
- ↑ 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 29726. PMID 11222759.
- ↑ 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.
- ↑ 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 3079562. PMID 21240261.
- ↑ 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 2587053. PMID 18953358.
- ↑ 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 3006227. PMID 20559380.
- ↑ 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 3245791. PMID 22089136.