ArticleNature2013
Structure-guided discovery of the metabolite carboxy-SAM that modulates tRNA function.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 94 citations in OpenAlex.
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- Carboxymethylcytosine is a natural base modification and a handle for bacteriophage DNA hypermodification.Nature communications · 2025Article
- tRNA modification profiling reveals epitranscriptome regulatory networks in Pseudomonas aeruginosa.Nucleic acids research · 2025Article
- Chemotype- and Target-Driven Genome Mining for a New Natural Product Inhibitor of Bacterial Peptide Deformylase.Journal of the American Chemical Society · 2025Article
- Unusual cysteine modifications in natural product biosynthesis.RSC chemical biology · 2024Review
- An organic O donor for biological hydroxylation reactions.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- CLPP-Null Eukaryotes with Excess Heme Biosynthesis Show Reduced L-arginine Levels, Probably via CLPX-Mediated OAT Activation.Biomolecules · 2024Article
- Discovery of a non-canonical prototype long-chain monoacylglycerol lipase through a structure-based endogenous reaction intermediate complex.Nature communications · 2023Article
- Revealing Drivers for Carboxy-ACS chemical biology · 2023Article
- Structural basis for the selective methylation of 5-carboxymethoxyuridine in tRNA modification.Nucleic acids research · 2023Article
- Review
- Direct enzymatic sequencing of 5-methylcytosine at single-base resolution.Nature chemical biology · 2023Article
- Functional Diversification and Structural Origins of Plant Natural Product Methyltransferases.Molecules (Basel, Switzerland) · 2022Review
- Article
- Unique anticodon loop conformation with the flipped-out wobble nucleotide in the crystal structure of unbound tRNARNA (New York, N.Y.) · 2021Article
- From Natural Methylation to Versatile Alkylations Using Halide Methyltransferases.Chembiochem : a European journal of chemical biology · 2021Review
- Biotechnological applications of S-adenosyl-methionine-dependent methyltransferases for natural products biosynthesis and diversification.Bioresources and bioprocessing · 2021Review
- Harnessing methylation and AdoMet-utilising enzymes for selective modification in cascade reactions.Organic & biomolecular chemistry · 2021Review
- Discovery of an Unnatural DNA Modification Derived from a Natural Secondary Metabolite.Cell chemical biology · 2021Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The identification of novel metabolites and the characterization of their biological functions are major challenges in biology. X-ray crystallography can reveal unanticipated ligands that persist through purification and crystallization. These adventitious protein-ligand complexes provide insights into new activities, pathways and regulatory mechanisms. We describe a new metabolite, carboxy-S-adenosyl-l-methionine (Cx-SAM), its biosynthetic pathway and its role in transfer RNA modification. The structure of CmoA, a member of the SAM-dependent methyltransferase superfamily, revealed a ligand consistent with Cx-SAM in the catalytic site. Mechanistic analyses showed an unprecedented role for prephenate as the carboxyl donor and the involvement of a unique ylide intermediate as the carboxyl acceptor in the CmoA-mediated conversion of SAM to Cx-SAM. A second member of the SAM-dependent methyltransferase superfamily, CmoB, recognizes Cx-SAM and acts as a carboxymethyltransferase to convert 5-hydroxyuridine into 5-oxyacetyl uridine at the wobble position of multiple tRNAs in Gram-negative bacteria, resulting in expanded codon-recognition properties. CmoA and CmoB represent the first documented synthase and transferase for Cx-SAM. These findings reveal new functional diversity in the SAM-dependent methyltransferase superfamily and expand the metabolic and biological contributions of SAM-based biochemistry. These discoveries highlight the value of structural genomics approaches in identifying ligands within the context of their physiologically relevant macromolecular binding partners, and in revealing their functions.
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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.