ArticlePloS one2018
Bacterial versus human thymidylate synthase: Kinetics and functionality.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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.
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Who cites it
14 citing papers in PubMed, 47 citations in OpenAlex.
- Disordered N-Terminal Tail "Wags the Dog" in Human Thymidylate Synthase.Biochemistry · 2026Article
- Shrimycocin-A, a next generation broad spectrum and systemic biofungicide from coconut shell agro waste for crop protection.Scientific reports · 2026Article
- Bacimethrin, an allelopathic vitamin B1 antagonist, is linked with microbial gene expression patterns in a hypereutrophic watershed.PloS one · 2025Article
- Effect of 5-fluorouracil onFrontiers in microbiology · 2025Review
- 5-Fluorouracil Inhibits Bacterial Growth and Reduces Biofilm in Addition to Having Synergetic Effects with Gentamicin AgainstMicroorganisms · 2024Article
- Multifunctional in vitro, in silico and DFT analyses on antimicrobial BagremycinA biosynthesized by Micromonospora chokoriensis CR3 from Hieracium canadense.Scientific reports · 2024Article
- Enzyme kinetics of deoxyuridine triphosphatase from Western corn rootworm.BMC research notes · 2023Article
- MRF: a tool to overcome the barrier of inconsistent genome annotations and perform comparative genomics studies for the largest animal DNA virus.Virology journal · 2023Article
- The cancer chemotherapeutic 5-fluorouracil is a potent Fusobacterium nucleatum inhibitor and its activity is modified by intratumoral microbiota.Cell reports · 2022Article
- Host and gut bacteria share metabolic pathways for anti-cancer drug metabolism.Nature microbiology · 2022Article
- Cytosolic localization and in vitro assembly of human de novo thymidylate synthesis complex.The FEBS journal · 2022Article
- Detection of Genomic Uracil Patterns.International journal of molecular sciences · 2021Review
- Proteomics of Sentinel Lymph Nodes in Early Breast Cancer for Identification of Thymidylate Synthase as a Potential Biomarker to Flag Metastasis: A Preliminary Study.Cancer management and research · 2020Article
- Targeting Methyltransferases in Human Pathogenic Bacteria: Insights into Thymidylate Synthase (TS) and Flavin-Dependent TS (FDTS).Molecules (Basel, Switzerland) · 2019Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Thymidylate Synthase (TSase) is a highly conserved enzyme that catalyzes the production of the DNA building block thymidylate. Structurally, functionally and mechanistically, bacterial and mammalian TSases share remarkable similarities. Because of this closeness, bacterial enzymes have long been used as model systems for human TSase. Furthermore, while TSase inhibitors have long served as chemotherapeutic drugs, no TSase inhibitor serves as an antibiotic. Despite their high resemblance, the mammalian TSases are distinct in a few known aspects, such as having a N-terminal tail and two insertions in the primary sequence and active/inactive conformations. Here, we aim to comprehensively characterize human (hs) TSase and delineate its contrasts and the similarities to the well-studied Escherichia coli (ec) TSase. We found that, in contrast to ecTSase, Mg2+ does not enhance reaction rates for hsTSase. The temperature dependence of intrinsic kinetic isotope effects (KIEs), on the other hand, suggests that Mg2+ has little or no impact on the transition state of hydride transfer in either enzyme, and that the transition state for the hydride transfer in hsTSase is looser than in ecTSase. Additionally, the substrates' binding order is strictly ordered for ecTSase but slightly less ordered for hsTSase. The observed kinetic and functional differences between bacterial and human enzymes may aid in the development of antibiotic drugs with reduced toxicity.
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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.