ArticleMethods in enzymology2018
Atlas of the Radical SAM Superfamily: Divergent Evolution of Function Using a "Plug and Play" Domain.
Article in Methods in enzymology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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91 citing papers in PubMed, 123 citations in OpenAlex.
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- The cobalamin-binding domain of cobalamin-dependent radical S-adenosylmethionine enzymes: Familiarity in unfamiliar places.Journal of inorganic biochemistry · 2026Review
- Structural Basis for CbioRxiv : the preprint server for biology · 2026Article
- Structural basis for iterative methylation by a cobalamin-dependent radicalProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Rgg/SHP transcriptional regulators, RaS-RiPPs, and their impacts in streptococci.F1000Research · 2026Review
- Structural Basis for Iterative Methylation by a Cobalamin-dependent Radical S-Adenosylmethionine Enzyme in Cystobactamids Biosynthesis.bioRxiv : the preprint server for biology · 2025Article
- Characterization of C3' Epimerization of the Thioheptose Core in the Biosynthesis of AlbomycinACS catalysis · 2025Article
- The radical SAM enzyme NirJ cleaves off two propionate side chains with the release of acrylate during heme dThe FEBS journal · 2025Article
- Structural basis for catalysis by human lipoyl synthase.Nature communications · 2025Article
- RadicalJournal of the American Chemical Society · 2025Article
- EPR Characterization of the BlsE Substrate Radical Offers Insight into the Determinants of Reaction Outcome that Distinguish Radical SAM Dioldehydratases from Dehydrogenases.Journal of the American Chemical Society · 2025Article
- Structural Evidence for DUF512 as a RadicalACS bio & med chem Au · 2024Article
- Initiation, Propagation, and Termination in the Chemistry of Radical SAM Enzymes.Biochemistry · 2024Review
- Discovery of a New Class of Aminoacyl Radical Enzymes Expands Nature's Known Radical Chemistry.Journal of the American Chemical Society · 2024Article
- Mechanistic Insights from the Crystal Structure and Computational Analysis of the Radical SAM Deaminase DesII.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Substrate Specificities of Variants of Barley (1,3)- and (1,3;1,4)-β-d-Glucanases Resulting from Mutagenesis and Segment Hybridization.Biochemistry · 2024Article
- Article
- CNature communications · 2024Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The radical SAM superfamily contains over 100,000 homologous enzymes that catalyze a remarkably broad range of reactions required for life, including metabolism, nucleic acid modification, and biogenesis of cofactors. While the highly conserved SAM-binding motif responsible for formation of the key 5'-deoxyadenosyl radical intermediate is a key structural feature that simplifies identification of superfamily members, our understanding of their structure-function relationships is complicated by the modular nature of their structures, which exhibit varied and complex domain architectures. To gain new insight about these relationships, we classified the entire set of sequences into similarity-based subgroups that could be visualized using sequence similarity networks. This superfamily-wide analysis reveals important features that had not previously been appreciated from studies focused on one or a few members. Functional information mapped to the networks indicates which members have been experimentally or structurally characterized, their known reaction types, and their phylogenetic distribution. Despite the biological importance of radical SAM chemistry, the vast majority of superfamily members have never been experimentally characterized in any way, suggesting that many new reactions remain to be discovered. In addition to 20 subgroups with at least one known function, we identified additional subgroups made up entirely of sequences of unknown function. Importantly, our results indicate that even general reaction types fail to track well with our sequence similarity-based subgroupings, raising major challenges for function prediction for currently identified and new members that continue to be discovered. Interactive similarity networks and other data from this analysis are available from the Structure-Function Linkage Database.
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