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Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
Radical SAM enzymes in methylation and methylthiolation
Rachel U Hutcheson1, Joan B Broderick
1Department of Chemistry and Biochemistry and the Astrobiology Biogeocatalysis Research Center, Montana State University, Bozeman, MT 59717, USA.
Metallomics : Integrated Biometal Science
|September 21, 2012
Summary
Radical S-adenosyl-l-methionine (SAM) enzymes utilize a [4Fe-4S] cluster to cleave SAM, generating a radical that initiates diverse biochemical reactions. This review highlights recent advances, particularly in methylation and methythiolation pathways.
Area of Science:
- Biochemistry
- Enzymology
- Organic Chemistry
Background:
- Radical S-adenosyl-l-methionine (SAM) enzymes are a diverse superfamily catalyzing various reactions.
- They share conserved structural and mechanistic features, including a site-differentiated [4Fe-4S] cluster.
Purpose of the Study:
- To present recent advancements in the understanding of radical SAM enzymes.
- To emphasize enzymes involved in methylation and methythiolation reactions.
Main Methods:
- Analysis of conserved [4Fe-4S] cluster structure and SAM binding.
- Investigation of the reductive cleavage of SAM to a 5'-deoxyadenosyl radical.
- Review of recent literature on radical SAM enzyme mechanisms.
Main Results:
- The [4Fe-4S] cluster in its (1+) state reductively cleaves SAM.
- This cleavage generates a 5'-deoxyadenosyl radical crucial for catalysis.
- Recent studies have elucidated mechanisms for methylation and methythiolation.
Conclusions:
- Radical SAM enzymes employ a conserved radical mechanism initiated by SAM cleavage.
- Ongoing research continues to uncover the breadth of their functions and catalytic strategies.
- Methylation and methythiolation are key areas of recent discovery within this enzyme class.
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