ArticleProceedings of the National Academy of Sciences of the United States of America2012
Folate binding site of flavin-dependent thymidylate synthase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- Direct Phasing of Protein Crystals with Continuous Iterative Projection Algorithms and Refined Envelope Reconstruction.Biomolecules · 2026Article
- The Oxidase Reaction of Flavin-Dependent Thymidylate Synthase Reveals the Nature of Inhibitor Binding.Biochemistry · 2025Article
- Selective Inhibitor Design against Thymidylate Synthase ofACS omega · 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
- dUMP/F-dUMP Binding to Thymidylate Synthase: Human VersusACS omega · 2020Article
- Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications.International journal of molecular sciences · 2019Review
- Drugging the Folate Pathway in Mycobacterium tuberculosis: The Role of Multi-targeting Agents.Cell chemical biology · 2019Article
- Crystal structure of the flavin-dependent thymidylate synthase Thy1 from Thermus thermophilus with an extra C-terminal domain.Acta crystallographica. Section F, Structural biology communications · 2019Article
- Targeting Methyltransferases in Human Pathogenic Bacteria: Insights into Thymidylate Synthase (TS) and Flavin-Dependent TS (FDTS).Molecules (Basel, Switzerland) · 2019Review
- 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
- From chemical metabolism to life: the origin of the genetic coding process.Beilstein journal of organic chemistry · 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
- Article
- Substrate activation in flavin-dependent thymidylate synthase.Journal of the American Chemical Society · 2014Article
- [Clinical significance of ERCC1, RRM1 and TS in non-small cell lung cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2014Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The DNA nucleotide thymidylate is synthesized by the enzyme thymidylate synthase, which catalyzes the reductive methylation of deoxyuridylate using the cofactor methylene-tetrahydrofolate (CH(2)H(4)folate). Most organisms, including humans, rely on the thyA- or TYMS-encoded classic thymidylate synthase, whereas, certain microorganisms, including all Rickettsia and other pathogens, use an alternative thyX-encoded flavin-dependent thymidylate synthase (FDTS). Although several crystal structures of FDTSs have been reported, the absence of a structure with folates limits understanding of the molecular mechanism and the scope of drug design for these enzymes. Here we present X-ray crystal structures of FDTS with several folate derivatives, which together with mutagenesis, kinetic analysis, and computer modeling shed light on the cofactor binding and function. The unique structural data will likely facilitate further elucidation of FDTSs' mechanism and the design of structure-based inhibitors as potential leads to new antimicrobial drugs.
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What OpenQuestion holds
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.