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Published on: September 7, 2017
Radical SAM-mediated methylation reactions.
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158-2280, USA. Danica.Fujimori@ucsf.edu
Current Opinion in Chemical Biology
|July 10, 2013
Summary
Radical S-adenosylmethionine (SAM) enzymes methylate distinct substrates using unique mechanisms. Recent studies reveal how RlmN, Cfr, and TsrM enzymes utilize SAM for radical methylation, advancing our understanding of these processes.
Area of Science:
- Biochemistry
- Enzymology
- Molecular Biology
Background:
- Radical S-adenosylmethionine (SAM) enzymes catalyze methylation reactions distinct from polar mechanisms.
- Recent in vitro reconstitutions have elucidated the catalytic mechanisms of several radical SAM methylating enzymes.
Purpose of the Study:
- To investigate the distinct mechanisms of radical SAM methylating enzymes.
- To understand the roles of S-adenosylmethionine (SAM) and methylcobalamin in radical methylation reactions.
Main Methods:
- In vitro reconstitution of enzyme activities.
- Mechanistic investigations of radical SAM methylating enzymes RlmN, Cfr, and TsrM.
Main Results:
- RlmN and Cfr enzymes utilize SAM as both a methyl group donor and a source of 5'-deoxyadenosyl radical (5'-dA) for RNA methylation via a methyl synthase mechanism.
- TsrM enzyme methylates tryptophan using methylcobalamin as an intermediate, potentially transferring the methyl group as a radical without reductive cleavage of SAM.
Conclusions:
- Radical SAM enzymes exhibit diverse methylation strategies, including methyl synthase mechanisms and novel pathways involving methylcobalamin.
- These findings provide crucial insights into the mechanisms of radical methylation and pave the way for future research in this area.
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