ArticleBioscience reports2014
Analysis of mRNA recognition by human thymidylate synthase.
Article in Bioscience reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
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- 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
- Detection of a G-Quadruplex as a Regulatory Element inInternational journal of molecular sciences · 2020Article
- The polymorphism of rs11614913 T/T in pri-American journal of translational research · 2020Article
- Structural and Functional Characterization of the Human Thymidylate Synthase (hTS) Interface Variant R175C, New Perspectives for the Development of hTS Inhibitors.Molecules (Basel, Switzerland) · 2019Article
- Evidence of Destabilization of the Human Thymidylate Synthase (hTS) Dimeric Structure Induced by the Interface Mutation Q62R.Biomolecules · 2019Article
- The Inescapable Effects of Ribosomes on In-Cell NMR Spectroscopy and the Implications for Regulation of Biological Activity.International journal of molecular sciences · 2019Review
- P53 represses pyrimidine catabolic gene dihydropyrimidine dehydrogenase (DPYD) expression in response to thymidylate synthase (TS) targeting.Scientific reports · 2017Article
- Structural analyses of human thymidylate synthase reveal a site that may control conformational switching between active and inactive states.The Journal of biological chemistry · 2017Article
- Trypanosoma brucei DHFR-TS Revisited: Characterisation of a Bifunctional and Highly Unstable Recombinant Dihydrofolate Reductase-Thymidylate Synthase.PLoS neglected tropical diseases · 2016Article
- Structural Analysis of Thymidylate Synthase from Kaposi's Sarcoma-Associated Herpesvirus with the Anticancer Drug Raltitrexed.PloS one · 2016Article
- Bacterial Thymidylate Synthase Binds Two Molecules of Substrate and Cofactor without Cooperativity.Journal of the American Chemical Society · 2015Article
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Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Expression of hTS (human thymidylate synthase), a key enzyme in thymidine biosynthesis, is regulated on the translational level through a feedback mechanism that is rarely found in eukaryotes. At low substrate concentrations, the ligand-free enzyme binds to its own mRNA and stabilizes a hairpin structure that sequesters the start codon. When in complex with dUMP (2'-deoxyuridine-5'-monophosphate) and a THF (tetrahydrofolate) cofactor, the enzyme adopts a conformation that is unable to bind and repress expression of mRNA. Here, we have used a combination of X-ray crystallography, RNA mutagenesis and site-specific cross-linking studies to investigate the molecular recognition of TS mRNA by the hTS enzyme. The interacting mRNA region was narrowed to the start codon and immediately flanking sequences. In the hTS enzyme, a helix-loop-helix domain on the protein surface was identified as the putative RNA-binding site.
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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.