ArticleScience (New York, N.Y.)2016
An unprecedented mechanism of nucleotide methylation in organisms containing thyX.
Article in Science (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- A Riboflavin-Derived Flavinium Salt Mediates Chemoselective Methylation Reactions.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- The Oxidase Reaction of Flavin-Dependent Thymidylate Synthase Reveals the Nature of Inhibitor Binding.Biochemistry · 2025Article
- Characterization and Genomic Analysis of a Lytic Vibriophage vB_VneS_S3 of Infecting Vibrio neocaledonicus.Current microbiology · 2025Article
- Structural Plasticity of Flavin-Dependent Thymidylate Synthase Controlled by the Enzyme Redox State.Biomolecules · 2025Article
- Insights into the Mechanism of Installation of 5-Carboxymethylaminomethyl Uridine Hypermodification by tRNA-Modifying Enzymes MnmE and MnmG.Journal of the American Chemical Society · 2023Article
- Integrative Approach to Probe Alternative Redox Mechanisms in RNA Modifications.Accounts of chemical research · 2023Article
- Biochemical and structural characterization of meningococcal methylenetetrahydrofolate reductase.Protein science : a publication of the Protein Society · 2023Article
- Bacterial origins of thymidylate metabolism in Asgard archaea and Eukarya.Nature communications · 2023Article
- Flavin-enabled reductive and oxidative epoxide ring opening reactions.Nature communications · 2022Article
- Pathways of thymidine hypermodification.Nucleic acids research · 2022Article
- An enzymatic activation of formaldehyde for nucleotide methylation.Nature communications · 2021Article
- Mechanism of Naphthoquinone Selectivity of Thymidylate Synthase ThyX.Biophysical journal · 2020Article
- Flavin doesn't put all oxygens in one basket.Nature chemical biology · 2020Article
- Reductive Evolution and Diversification of C5-Uracil Methylation in the Nucleic Acids of Mollicutes.Biomolecules · 2020Article
- Multitargeting Compounds: A Promising Strategy to Overcome Multi-Drug Resistant Tuberculosis.Molecules (Basel, Switzerland) · 2020Review
- Inter-Active Site Communication Mediated by the Dimer Interface β-Sheet in the Half-the-Sites Enzyme, Thymidylate Synthase.Biochemistry · 2019Article
- Drugging the Folate Pathway in Mycobacterium tuberculosis: The Role of Multi-targeting Agents.Cell chemical biology · 2019Article
- Targeting Methyltransferases in Human Pathogenic Bacteria: Insights into Thymidylate Synthase (TS) and Flavin-Dependent TS (FDTS).Molecules (Basel, Switzerland) · 2019Review
- Cyclic Changes in Active Site Polarization and Dynamics Drive the 'Ping-pong' Kinetics in NRH:Quinone Oxidoreductase 2: An Insight from QM/MM Simulations.ACS catalysis · 2018Article
- Methionine Sulfoxide Reductases of Archaea.Antioxidants (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
In several human pathogens, thyX-encoded flavin-dependent thymidylate synthase (FDTS) catalyzes the last step in the biosynthesis of thymidylate, one of the four DNA nucleotides. ThyX is absent in humans, rendering FDTS an attractive antibiotic target; however, the lack of mechanistic understanding prohibits mechanism-based drug design. Here, we report trapping and characterization of two consecutive intermediates, which together with previous crystal structures indicate that the enzyme's reduced flavin relays a methylene from the folate carrier to the nucleotide acceptor. Furthermore, these results corroborate an unprecedented activation of the nucleotide that involves no covalent modification but only electrostatic polarization by the enzyme's active site. These findings indicate a mechanism that is very different from thymidylate biosynthesis in humans, underscoring the promise of FDTS as an antibiotic target.
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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.