ArticleMetallomics : integrated biometal science2022
Characterization of the nickel-inserting cyclometallase LarC from Moorella thermoacetica and identification of a cytidinylylated reaction intermediate.
Article in Metallomics : integrated biometal science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Discovery and characterization of a nickel enzyme family that catalyses intermolecular hydride shuttling.Nature chemistry · 2026Article
- Structural and functional analysis of LarC, a CTP-dependent cyclometallase required for nickel-pincer nucleotide cofactor biosynthesis.Science advances · 2026Article
- Structural Basis for the Catalysis and Substrate Specificity of a LarA Racemase with a Broad Substrate Spectrum.ACS catalysis · 2025Article
- Article
- A structural view of nickel-pincer nucleotide cofactor-related biochemistry.Critical reviews in biochemistry and molecular biology · 2024Review
- Structure of the LarB-Substrate Complex and Identification of a Reaction Intermediate during Nickel-Pincer Nucleotide Cofactor Biosynthesis.Biochemistry · 2023Article
- Irreversible inactivation of lactate racemase by sodium borohydride reveals reactivity of the nickel-pincer nucleotide cofactor.ACS catalysis · 2023Article
- Five decades of metalloenzymology.The Enzymes · 2023Review
- The nickel-pincer coenzyme of lactate racemase: A case study of uncovering cofactor structure and biosynthesis.Methods in enzymology · 2023Article
- Unveiling the mechanisms and biosynthesis of a novel nickel-pincer enzyme.Biochemical Society transactions · 2022Article
- Sulfur incorporation into biomolecules: recent advances.Critical reviews in biochemistry and molecular biologyReview
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
LarC catalyzes the CTP-dependent insertion of nickel ion into pyridinium-3,5-bisthiocarboxylic acid mononucleotide (P2TMN), the final biosynthetic step for generating the nickel-pincer nucleotide (NPN) enzyme cofactor. In this study, we characterized a LarC homolog from Moorella thermoacetica (LarCMt) and characterized selected properties of the protein. We ruled out the hypothesis that enzyme inhibition by its product pyrophosphate accounts for its apparent single-turnover activity. Most notably, we identified a cytidinylylated-substrate intermediate that is formed during the reaction of LarCMt. Selected LarCMt variants with substitutions at the predicted CTP-binding site retained substantial amounts of activity, but exhibited greatly reduced levels of the CMP-P2TMN intermediate. In contrast, enhanced amounts of the CMP-P2TMN intermediate were generated when using LarCMt from cells grown on medium without supplemental nickel. On the basis of these results, we propose a functional role for CTP in the unprecedented nickel-insertase reaction during NPN biosynthesis.
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