ArticleProceedings of the National Academy of Sciences of the United States of America2011
RNA methylation by radical SAM enzymes RlmN and Cfr proceeds via methylene transfer and hydride shift.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 102 citations in OpenAlex.
- Beyond native reactivity: radical SAM enzymes as platforms for new-to-nature chemistry.RSC chemical biology · 2026Review
- CNature communications · 2024Article
- An RNA modification enzyme directly senses reactive oxygen species for translational regulation in Enterococcus faecalis.Nature communications · 2023Article
- Biosynthesis of 3-thia-α-amino acids on a carrier peptide.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Functional Diversity of HemN-like Proteins.ACS bio & med chem Au · 2022Review
- Structural basis for context-specific inhibition of translation by oxazolidinone antibiotics.Nature structural & molecular biology · 2022Article
- Directed evolution of the rRNA methylating enzyme Cfr reveals molecular basis of antibiotic resistance.eLife · 2022Article
- miCLIP-MaPseq Identifies Substrates of Radical SAM RNA-Methylating Enzyme Using Mechanistic Cross-Linking and Mismatch Profiling.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Naturally occurring modified ribonucleosides.Wiley interdisciplinary reviews. RNA · 2020Review
- Analysis of RNA Methylation by Phylogenetically Diverse Cfr RadicalBiochemistry · 2019Article
- Matching tRNA modifications in humans to their known and predicted enzymes.Nucleic acids research · 2019Article
- Structural and biochemical analysis of the dual-specificity Trm10 enzyme fromRNA (New York, N.Y.) · 2018Article
- Investigation of Solvent Hydron Exchange in the Reaction Catalyzed by the Antibiotic Resistance Protein Cfr.Biochemistry · 2018Article
- miCLIP-MaPseq, a Substrate Identification Approach for Radical SAM RNA Methylating Enzymes.Journal of the American Chemical Society · 2018Article
- RNA-modifying proteins as anticancer drug targets.Nature reviews. Drug discovery · 2018Review
- Mechanism of a Class C Radical S-Adenosyl-l-methionine Thiazole Methyl Transferase.Journal of the American Chemical Society · 2017Article
- Mutations in RNA methylating enzymes in disease.Current opinion in chemical biology · 2017Review
- Antibiotic resistance evolved via inactivation of a ribosomal RNA methylating enzyme.Nucleic acids research · 2016Article
- Crystallographic capture of a radical S-adenosylmethionine enzyme in the act of modifying tRNA.Science (New York, N.Y.) · 2016Article
- Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
RlmN and Cfr are Radical SAM enzymes that modify a single adenosine nucleotide--A2503--in 23S ribosomal RNA. This nucleotide is positioned within the peptidyl transferase center of the ribosome, which is a target of numerous antibiotics. An unusual feature of these enzymes is their ability to carry out methylation of amidine carbons of the adenosine substrate. To gain insight into the mechanism of methylation catalyzed by RlmN and Cfr, deuterium labeling experiments were carried out. These experiments demonstrate that the newly introduced methyl group is assembled from an S-adenosyl-L-methionine (SAM)-derived methylene fragment and a hydrogen atom that had migrated from the substrate amidine carbon. Rather than activating the adenosine nucleotide of the substrate by hydrogen atom abstraction from an amidine carbon, the 5'-deoxyadenosyl radical abstracts hydrogen from the second equivalent of SAM to form the SAM-derived radical cation. This species, or its corresponding sulfur ylide, subsequently adds into the substrate, initiating hydride shift and S-adenosylhomocysteine elimination to complete the formation of the methyl group. These findings indicate that rather than acting as methyltransferases, RlmN and Cfr are methyl synthases. Together with the previously described 5'-deoxyadenosyl and 3-amino-3-carboxypropyl radicals, these findings demonstrate that all three carbon atoms attached to the sulfonium center in SAM can serve as precursors to carbon-derived radicals in enzymatic reactions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.