ArticleBiochemistry2018
A Radical Clock Probe Uncouples H Atom Abstraction from Thioether Cross-Link Formation by the Radical S-Adenosyl-l-methionine Enzyme SkfB.
Article in Biochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- RaS-RiPPs in Streptococci and the Human Microbiome.ACS bio & med chem Au · 2022Review
- Journey on the Radical SAM Road as an Accidental Pilgrim.ACS bio & med chem Au · 2022Review
- New Role for Radical SAM Enzymes in the Biosynthesis of Thio(seleno)oxazole RiPP Natural Products.Biochemistry · 2021Article
- Current Advancements in Sactipeptide Natural Products.Frontiers in chemistry · 2021Review
- New developments in RiPP discovery, enzymology and engineering.Natural product reports · 2021Review
- Ruminococcin C, a promising antibiotic produced by a human gut symbiont.Science advances · 2019Article
- Structural and spectroscopic analyses of the sporulation killing factor biosynthetic enzyme SkfB, a bacterial AdoMet radical sactisynthase.The Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Sporulation killing factor (SKF) is a ribosomally synthesized and post-translationally modified peptide (RiPP) produced by Bacillus. SKF contains a thioether cross-link between the α-carbon at position 40 and the thiol of Cys32, introduced by a member of the radical S-adenosyl-l-methionine (SAM) superfamily, SkfB. Radical SAM enzymes employ a 4Fe-4S cluster to bind and reductively cleave SAM to generate a 5'-deoxyadenosyl radical. SkfB utilizes this radical intermediate to abstract the α-H atom at Met40 to initiate cross-linking. In addition to the cluster that binds SAM, SkfB also has an auxiliary cluster, the function of which is not known. We demonstrate that a substrate analogue with a cyclopropylglycine (CPG) moiety replacing the wild-type Met40 side chain forgoes thioether cross-linking for an alternative radical ring opening of the CPG side chain. The ring opening reaction also takes place with a catalytically inactive SkfB variant in which the auxiliary Fe-S cluster is absent. Therefore, the CPG-containing peptide uncouples H atom abstraction from thioether bond formation, limiting the role of the auxiliary cluster to promoting thioether cross-link formation. CPG proves to be a valuable tool for uncoupling H atom abstraction from peptide modification in RiPP maturases and demonstrates potential to leverage RS enzyme reactivity to create noncanonical amino acids.
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Registered trials
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.