ArticleNature chemistry2012
Evidence that a 'dynamic knockout' in Escherichia coli dihydrofolate reductase does not affect the chemical step of catalysis.
Article in Nature chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- Dissecting mechanisms of ligand binding and conformational changes in the glutamine-binding protein.eLife · 2026Article
- Interplay of structural preorganization and conformational sampling in UDP-glucuronic acid 4-epimerase catalysis.Nature communications · 2024Article
- Perturbative diffraction methods resolve a conformational switch that facilitates a two-step enzymatic mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- X-ray-driven chemistry and conformational heterogeneity in atomic resolution crystal structures of bacterial dihydrofolate reductases.bioRxiv : the preprint server for biology · 2023Article
- Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation.Nature communications · 2022Article
- Cross-validation of distance measurements in proteins by PELDOR/DEER and single-molecule FRET.Nature communications · 2022Article
- Linker Molecules Convert Commercial Fluorophores into Tailored Functional Probes during Biolabelling.Angewandte Chemie (International ed. in English) · 2022Article
- Single-Molecule Sampling of Dihydrofolate Reductase Shows Kinetic Pauses and an Endosteric Effect Linked to Catalysis.ACS catalysis · 2022Article
- Structural dynamics in the evolution of a bilobed protein scaffold.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Temperature-Dependent Kinetic Isotope Effects in R67 Dihydrofolate Reductase from Path-Integral Simulations.The journal of physical chemistry. B · 2021Article
- Acceleration of catalysis in dihydrofolate reductase by transient, site-specific photothermal excitation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Designing Dihydrofolate Reductase Inhibitors as X-ray Radiosensitizers to Reverse Radioresistance of Cervical Cancer.ACS medicinal chemistry letters · 2020Article
- Heavy Enzymes and the Rational Redesign of Protein Catalysts.Chembiochem : a European journal of chemical biology · 2019Article
- Article
- Why are some Enzymes Dimers? Flexibility and Catalysis inACS catalysis · 2019Article
- Convergence of theory and experiment on the role of preorganization, quantum tunneling and enzyme motions into flavoenzyme-catalyzed hydride transfer.ACS catalysis · 2019Article
- Engineered control of enzyme structural dynamics and function.Protein science : a publication of the Protein Society · 2018Review
- Contribution of buried distal amino acid residues in horse liver alcohol dehydrogenase to structure and catalysis.Protein science : a publication of the Protein Society · 2018Article
- The role of the MetThe Journal of biological chemistry · 2017Article
- Electric Fields and Enzyme Catalysis.Annual review of biochemistry · 2017Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
The question of whether protein motions play a role in the chemical step of enzymatic catalysis has generated much controversy in recent years. Debate has recently reignited over possible dynamic contributions to catalysis in dihydrofolate reductase, following conflicting conclusions from studies of the N23PP/S148A variant of the Escherichia coli enzyme. By investigating the temperature dependence of kinetic isotope effects, we present evidence that the reduction in the hydride transfer rate constants in this variant is not a direct result of impairment of conformational fluctuations. Instead, the conformational state of the enzyme immediately before hydride transfer, which determines the electrostatic environment of the active site, affects the rate constant for the reaction. Although protein motions are clearly important for binding and release of substrates and products, there appears to be no detectable dynamic coupling of protein motions to the hydride transfer step itself.
Indexed as
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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.