ArticleeLife2022
Dynamic allostery in substrate binding by human thymidylate synthase.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 17 citations in OpenAlex.
- Dynamic view of an allosteric intermediate in a positively cooperative dimer.bioRxiv : the preprint server for biology · 2026Article
- Disordered N-Terminal Tail "Wags the Dog" in Human Thymidylate Synthase.Biochemistry · 2026Article
- The Power of Protein Dynamics in Binding and Allostery.Biochemistry · 2026Review
- Modernizing biomolecular NMR: The POKY suite.The Journal of biological chemistry · 2026Review
- Crystallographic Ensembles Reveal the Structural Basis of Binding Entropy in SARS-CoV2 Macrodomain.bioRxiv : the preprint server for biology · 2025Article
- Sparse networks of conformational fluctuations communicate signals within proteins.bioRxiv : the preprint server for biology · 2025Article
- A flexible, allosteric loop regulates protein activity and rewires electrostatics.Protein science : a publication of the Protein Society · 2025Article
- Advances in uncovering the mechanisms of macromolecular conformational entropy.Nature chemical biology · 2025Review
- Identifying Allosteric Hotspots inBiochemistry · 2025Article
- Platform-directed allostery and quaternary structure dynamics of SAMHD1 catalysis.Nature communications · 2024Article
- Gauging Dynamics-driven Allostery Using a New Computational Tool: A CAP Case Study.Journal of molecular biology · 2024Article
- Mixed, nonclassical behavior in a classic allosteric protein.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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
Human thymidylate synthase (hTS) is essential for DNA replication and therefore a therapeutic target for cancer. Effective targeting requires knowledge of the mechanism(s) of regulation of this 72 kDa homodimeric enzyme. Here, we investigate the mechanism of binding cooperativity of the nucleotide substrate. We have employed exquisitely sensitive methyl-based CPMG and CEST NMR experiments enabling us to identify residues undergoing bifurcated linear 3-state exchange, including concerted switching between active and inactive conformations in the apo enzyme. The inactive state is populated to only ~1.3%, indicating that conformational selection contributes negligibly to the cooperativity. Instead, methyl rotation axis order parameters, determined by
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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.