Emerging themes in radical SAM chemistry

Area of Science:

• Biochemistry
• Enzymology
• Structural Biology

Background:

• Radical SAM (RS) enzymes are a diverse superfamily catalyzing various reactions via radical chemistry.
• Key features include a [4Fe-4S] cluster coordinated by cysteine residues and S-adenosylmethionine (SAM).
• SAM acts as a precursor to the 5'-deoxyadenosyl radical, a crucial intermediate.

Purpose of the Study:

• To summarize the structural and mechanistic features of the radical SAM enzyme superfamily.
• To highlight the diversity of reactions catalyzed by RS enzymes.
• To underscore the importance of recently characterized members in expanding knowledge.

Main Methods:

• Review of existing literature on radical SAM enzymes.
• Analysis of conserved structural motifs, including the [4Fe-4S] cluster and triosephosphate isomerase (TIM) barrel.
• Examination of biochemical and mechanistic studies of characterized RS enzymes.

Main Results:

• RS enzymes share conserved structural elements like the [4Fe-4S] cluster and often a TIM barrel domain.
• The 5'-deoxyadenosyl radical generated from SAM is central to their catalytic mechanisms.
• Additional domains and Fe-S clusters are present in many RS enzymes, contributing to their functional diversity.

Conclusions:

• The radical SAM superfamily exhibits remarkable catalytic versatility driven by radical chemistry.
• Structural insights, particularly the TIM barrel and Fe-S clusters, are key to understanding RS enzyme function.
• Continued characterization of novel RS enzymes promises further expansion of their known reaction repertoire and mechanistic understanding.