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Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
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Surprise! A hidden B12 cofactor catalyzes a radical methylation.
1Department of Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822 jtj@hawaii.edu.
The Journal of Biological Chemistry
|August 4, 2019
Summary
Radical S-adenosylmethionine methylases are enzymes that add methyl groups. A new enzyme, Mmp10, uses a methylcobalamin cofactor for methylation, suggesting a novel subclass of these enzymes.
Area of Science:
- Biochemistry
- Enzymology
- Methylation Reactions
Background:
- Radical S-adenosylmethionine (SAM) methylases are crucial enzymes catalyzing methylation at unactivated carbon and phosphorus atoms.
- Class B RS methylases utilize a unique mechanism involving cobalamin for methyl transfer to substrate radicals.
Purpose of the Study:
- To investigate the mechanism and cofactor requirements of Mmp10, an RS enzyme involved in methyl coenzyme M reductase.
- To determine if Mmp10 represents a new subclass of B12-dependent RS methylases.
Main Methods:
- Biochemical assays to study Mmp10 activity.
- Cofactor binding studies.
- Sequence homology analysis.
Main Results:
- Mmp10 binds a methylcobalamin cofactor, essential for methyl transfer from SAM to a peptide substrate.
- Mmp10 catalyzes the methylation of Arg-285 in methyl coenzyme M reductase.
- Mmp10 exhibits limited sequence homology to known methylases.
Conclusions:
- Mmp10 functions as a B12-dependent radical SAM methylase.
- The findings suggest Mmp10 represents a novel subclass of B12-dependent RS methylases.
- This discovery expands our understanding of methyltransferase diversity and function.
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