ArticleBiochemistry2008
The R163K mutant of human thymidylate synthase is stabilized in an active conformation: structural asymmetry and reactivity of cysteine 195.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
15 citing papers in PubMed.
- Disordered N-Terminal Tail "Wags the Dog" in Human Thymidylate Synthase.Biochemistry · 2026Article
- Article
- Article
- Biomolecular study of human thymidylate synthase conformer-selective inhibitors: New chemotherapeutic approach.PloS one · 2018Article
- Crystal structure of the active form of native human thymidylate synthase in the absence of bound substrates.Acta crystallographica. Section F, Structural biology communications · 2017Article
- Analysis of mRNA recognition by human thymidylate synthase.Bioscience reports · 2014Article
- Virtual screening reveals allosteric inhibitors of the Toxoplasma gondii thymidylate synthase-dihydrofolate reductase.Bioorganic & medicinal chemistry letters · 2014Article
- Selective peptide inhibitors of bifunctional thymidylate synthase-dihydrofolate reductase from Toxoplasma gondii provide insights into domain-domain communication and allosteric regulation.Protein science : a publication of the Protein Society · 2013Article
- The structure of Enterococcus faecalis thymidylate synthase provides clues about folate bacterial metabolism.Acta crystallographica. Section D, Biological crystallography · 2012Article
- Protein-protein interface-binding peptides inhibit the cancer therapy target human thymidylate synthase.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Evolution of metamorphism in thymidylate synthases within the primate lineages.Journal of molecular evolution · 2011Article
- Structures of human thymidylate synthase R163K with dUMP, FdUMP and glutathione show asymmetric ligand binding.Acta crystallographica. Section D, Biological crystallography · 2011Article
- Human thymidylate synthase with loop 181-197 stabilized in an inactive conformation: ligand interactions, phosphorylation, and inhibition profiles.Protein science : a publication of the Protein Society · 2011Article
- Replacement of Val3 in human thymidylate synthase affects its kinetic properties and intracellular stability .Biochemistry · 2010Article
- Variants of human thymidylate synthase with loop 181-197 stabilized in the inactive conformation.Protein science : a publication of the Protein Society · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Loop 181-197 of human thymidylate synthase (hTS) populates two conformational states. In the first state, Cys195, a residue crucial for catalytic activity, is in the active site (active conformer); in the other conformation, it is about 10 A away, outside the active site (inactive conformer). We have designed and expressed an hTS variant, R163K, in which the inactive conformation is destabilized. The activity of this mutant is 33% higher than that of wt hTS, suggesting that at least one-third of hTS populates the inactive conformer. Crystal structures of R163K in two different crystal forms, with six and two subunits per asymmetric part of the unit cells, have been determined. All subunits of this mutant are in the active conformation while wt hTS crystallizes as the inactive conformer in similar mother liquors. The structures show differences in the environment of catalytic Cys195, which correlate with Cys195 thiol reactivity, as judged by its oxidation state. Calculations show that the molecular electrostatic potential at Cys195 differs between the subunits of the dimer. One of the dimers is asymmetric with a phosphate ion bound in only one of the subunits. In the absence of the phosphate ion, that is in the inhibitor-free enzyme, the tip of loop 47-53 is about 11 A away from the active site.
Indexed as
Identifiers
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.