Radical SAM enzymes

[1][2] These enzymes utilize this radical intermediate[3] to perform diverse transformations, often to functionalize unactivated C-H bonds.

[4] According to the EFI and SFLD databases, more than 220,000 radical SAM enzymes are predicted to be involved in 85 types of biochemical transformations.

Methylthiotransferases play a major role in catalyzing methylthiolation on tRNA nucleotides or anticodons through a redox mechanism.

Two well-known examples are BioB and LipA which are independently responsible for biotin synthesis and lipoic acid metabolism, respectively.

SPASM/Twitch enzymes carry a functionalized C-terminal extension for the binding of two [4Fe-4S] clusters, especially in post-translational modifications of peptides.

[46][47][48][7] The following examples are representative enzymes that can catalyze peptide modifications to generate specific natural products or cofactors.

[7] Another subset of radical SAM superfamily has been shown to catalyze carbon skeleton rearrangements especially in the areas of DNA repair and cofactor biosynthesis.

Below are a few examples of radical SAM enzymes have been shown to be promising targets for antibiotic and antiviral development.

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.

Superimposition of three radical SAM core domains. Side views of radical SAM enzymes BioB ( PDB: 1R30 ), MoaA ( PDB: 1TV8 ) and phTYW1 ( PDB: 2YX0 ) are shown front and back. This core fold consists of six β/α motifs arranged in a manner that is similar to TIM barrel and is responsible for radical generation. [ 10 ] β-sheets are colored yellow and α-helices are shown in cyan.
Structure of a B 12 -dependent radical SAM enzyme (PDB: 7QBS )