ArticleJournal of the American Chemical Society2012
Trapping of an intermediate in the reaction catalyzed by flavin-dependent thymidylate synthase.
Article in Journal of the American Chemical Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- The Oxidase Reaction of Flavin-Dependent Thymidylate Synthase Reveals the Nature of Inhibitor Binding.Biochemistry · 2025Article
- Structural Plasticity of Flavin-Dependent Thymidylate Synthase Controlled by the Enzyme Redox State.Biomolecules · 2025Article
- Integrative Approach to Probe Alternative Redox Mechanisms in RNA Modifications.Accounts of chemical research · 2023Article
- An enzymatic activation of formaldehyde for nucleotide methylation.Nature communications · 2021Article
- Chemo-enzymatic synthesis of the exocyclic olefin isomer of thymidine monophosphate.Bioorganic & medicinal chemistry · 2018Article
- Unique Features and Anti-microbial Targeting of Folate- and Flavin-Dependent Methyltransferases Required for Accurate Maintenance of Genetic Information.Frontiers in microbiology · 2018Review
- Flavin-dependent thymidylate synthase: N5 of flavin as a Methylene carrier.Archives of biochemistry and biophysics · 2017Review
- Deprotonations in the Reaction of Flavin-Dependent Thymidylate Synthase.Biochemistry · 2016Article
- Flavin-Dependent Thymidylate Synthase as a New Antibiotic Target.Molecules (Basel, Switzerland) · 2016Review
- An unprecedented mechanism of nucleotide methylation in organisms containing thyX.Science (New York, N.Y.) · 2016Article
- Synthesis and application of isotopically labeled flavin nucleotides.Journal of labelled compounds & radiopharmaceuticals · 2015Article
- Targeting of Helicobacter pylori thymidylate synthase ThyX by non-mitotoxic hydroxy-naphthoquinones.Open biology · 2015Article
- Role of long-range protein dynamics in different thymidylate synthase catalyzed reactions.International journal of molecular sciences · 2015Article
- Article
- Substrate activation in flavin-dependent thymidylate synthase.Journal of the American Chemical Society · 2014Article
- Flavin-Dependent Thymidylate Synthase as a Drug Target for Deadly Microbes: Mutational Study and a Strategy for Inhibitor Design.Journal of bioterrorism & biodefense · 2013Article
- QM/MM calculations suggest a novel intermediate following the proton abstraction catalyzed by thymidylate synthase.Biochemistry · 2013Article
- Article
- Folate binding site of flavin-dependent thymidylate synthase.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Thymidylate is a DNA nucleotide that is essential to all organisms and is synthesized by the enzyme thymidylate synthase (TSase). Several human pathogens rely on an alternative flavin-dependent thymidylate synthase (FDTS), which differs from the human TSase both in structure and molecular mechanism. It has recently been shown that FDTS catalysis does not rely on an enzymatic nucleophile and that the proposed reaction intermediates are not covalently bound to the enzyme during catalysis, an important distinction from the human TSase. Here we report the chemical trapping, isolation, and identification of a derivative of such an intermediate in the FDTS-catalyzed reaction. The chemically modified reaction intermediate is consistent with currently proposed FDTS mechanisms that do not involve an enzymatic nucleophile, and it has never been observed during any other TSase reaction. These findings establish the timing of the methylene transfer during FDTS catalysis. The presented methodology provides an important experimental tool for further studies of FDTS, which may assist efforts directed toward the rational design of inhibitors as leads for future antibiotics.
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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.