Radical SAM
| Radical_SAM | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Radical_SAM | ||||||||
| Pfam | PF04055 | ||||||||
| InterPro | IPR007197 | ||||||||
| SCOP | 102114 | ||||||||
| SUPERFAMILY | 102114 | ||||||||
|
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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:
- 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)
- Cfr - 23S rRNA (adenine(2503)-C(8))-methyltransferase - rRNA modification for antibiotic resistance
- 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)
- MqnE - aminofutalosine synthase (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)
- PflA - pyruvate formate-lyase activating enzyme (enzyme activation)
- PhpK - radical SAM P-methyltransferase - antibiotic biosynthesis
- PqqE - PQQ biosynthesis enzyme (peptide modification / cofactor biosynthesis - PQQ)
- PylB - pyrrolysine biosynthesis protein PylB (amino acid biosynthesis - pyrrolysine)
- QhpD (PeaB) - quinohemoprotein amine dehydrogenase maturation protein (enzyme activation)
- QueE - 7-carboxy-7-deazaguanine (CDG) synthase
- RimO - ribosomal protein S12 methylthiotransferase
- RlmN - 23S rRNA (adenine(2503)-C(2))-methyltransferase (rRNA modification)
- ScfB - SCIFF maturase (peptide modification by thioether cross-link formation) [5]
- SkfB - sporulation killing factor maturase
- SplB - spore photoproduct lyase (DNA repair)
- ThiH - thiazole biosynthesis protein ThiH (cofactor biosynthesis - thiamine)
- TrnC - thuricin biosynthesis
- TrnD - thuricin biosynthesis
- 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) [6]
- Dph2 (PF01866) - diphthamide biosynthesis enzyme Dph2 (protein modification - diphthamide in translation elongation factor 2) (note different radical production, a 3-amino-3-carboxypropyl radical) [7]
- PhnJ (PF06007) - phosphonate metabolism protein PhnJ (C-P phosphonate bond cleavage) [8]
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