ArticleBiochemistry2014
Evidence for a catalytically and kinetically competent enzyme-substrate cross-linked intermediate in catalysis by lipoyl synthase.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Amino Acids in the RSSY Motif of Lipoyl Synthase Control Substrate Binding and ReactivitybioRxiv : the preprint server for biology · 2026Article
- Structural basis for catalysis by human lipoyl synthase.Nature communications · 2025Article
- Lipoic acid attachment to proteins: stimulating new developments.Microbiology and molecular biology reviews : MMBR · 2024Review
- Cluster-selectiveChemical science · 2023Article
- Identification of a novel lipoic acid biosynthesis pathway reveals the complex evolution of lipoate assembly in prokaryotes.PLoS biology · 2023Article
- Characterization of LipS1 and LipS2 fromACS bio & med chem Au · 2022Article
- In Vitro Demonstration of Human Lipoyl Synthase Catalytic Activity in the Presence of NFU1.ACS bio & med chem Au · 2022Article
- Reversible Alkyl-Group Migration between Iron and Sulfur in [FeJournal of the American Chemical Society · 2022Article
- Genome-wide association studies of grain quality traits in maize.Scientific reports · 2021Article
- Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly.International journal of molecular sciences · 2021Article
- Biochemical Approaches to Probe the Role of the Auxiliary Iron-Sulfur Cluster of Lipoyl Synthase from Mycobacterium Tuberculosis.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Characterization of Fe-S Clusters in Proteins by Mӧssbauer Spectroscopy.Methods in molecular biology (Clifton, N.J.) · 2021Article
- A Structurally Novel Lipoyl Synthase in the Hyperthermophilic Archaeon Thermococcus kodakarensis.Applied and environmental microbiology · 2020Article
- First Step in Catalysis of the RadicalJournal of the American Chemical Society · 2020Article
- Article
- The A-type domain inThe Journal of biological chemistry · 2019Article
- Advances in synthesis of biotin and assembly of lipoic acid.Current opinion in chemical biology · 2018Review
- Structural and spectroscopic analyses of the sporulation killing factor biosynthetic enzyme SkfB, a bacterial AdoMet radical sactisynthase.The Journal of biological chemistry · 2018Article
- Following the electrons: peculiarities in the catalytic cycles of radical SAM enzymes.Natural product reports · 2018Review
- Insight into the reaction mechanism of lipoyl synthase: a QM/MM study.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Article
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6 authors.
Funding
Abstract
Lipoyl synthase (LS) catalyzes the final step in lipoyl cofactor biosynthesis: the insertion of two sulfur atoms at C6 and C8 of an (N(6)-octanoyl)-lysyl residue on a lipoyl carrier protein (LCP). LS is a member of the radical SAM superfamily, enzymes that use a [4Fe-4S] cluster to effect the reductive cleavage of S-adenosyl-l-methionine (SAM) to l-methionine and a 5'-deoxyadenosyl 5'-radical (5'-dA(•)). In the LS reaction, two equivalents of 5'-dA(•) are generated sequentially to abstract hydrogen atoms from C6 and C8 of the appended octanoyl group, initiating sulfur insertion at these positions. The second [4Fe-4S] cluster on LS, termed the auxiliary cluster, is proposed to be the source of the inserted sulfur atoms. Herein, we provide evidence for the formation of a covalent cross-link between LS and an LCP or synthetic peptide substrate in reactions in which insertion of the second sulfur atom is slowed significantly by deuterium substitution at C8 or by inclusion of limiting concentrations of SAM. The observation that the proteins elute simultaneously by anion-exchange chromatography but are separated by aerobic SDS-PAGE is consistent with their linkage through the auxiliary cluster that is sacrificed during turnover. Generation of the cross-linked species with a small, unlabeled (N(6)-octanoyl)-lysyl-containing peptide substrate allowed demonstration of both its chemical and kinetic competence, providing strong evidence that it is an intermediate in the LS reaction. Mössbauer spectroscopy of the cross-linked intermediate reveals that one of the [4Fe-4S] clusters, presumably the auxiliary cluster, is partially disassembled to a 3Fe-cluster with spectroscopic properties similar to those of reduced [3Fe-4S](0) clusters.
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