ArticleJournal of the American Chemical Society2013
Increased dynamic effects in a catalytically compromised variant of Escherichia coli dihydrofolate reductase.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- Electrostatics as a Guiding Principle in Understanding and Designing Enzymes.Journal of chemical theory and computation · 2024Review
- Cryo-kinetics Reveal Dynamic Effects on the Chemistry of Human Dihydrofolate Reductase.Chembiochem : a European journal of chemical biology · 2021Article
- Temperature-Dependent Kinetic Isotope Effects in R67 Dihydrofolate Reductase from Path-Integral Simulations.The journal of physical chemistry. B · 2021Article
- Protein Mass-Modulated Effects in Alkaline Phosphatase.Biochemistry · 2021Article
- Heavy Enzymes and the Rational Redesign of Protein Catalysts.Chembiochem : a European journal of chemical biology · 2019Article
- Why are some Enzymes Dimers? Flexibility and Catalysis inACS catalysis · 2019Article
- Conformational dynamics and enzyme evolution.Journal of the Royal Society, Interface · 2018Review
- Isotope Substitution of Promiscuous Alcohol Dehydrogenase Reveals the Origin of Substrate Preference in the Transition State.Angewandte Chemie (International ed. in English) · 2018Article
- Protein Mass Effects on Formate Dehydrogenase.Journal of the American Chemical Society · 2017Article
- Quantifying the limits of transition state theory in enzymatic catalysis.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The role of the MetThe Journal of biological chemistry · 2017Article
- Dynamic and Electrostatic Effects on the Reaction Catalyzed by HIV-1 Protease.Journal of the American Chemical Society · 2016Article
- Minimization of dynamic effects in the evolution of dihydrofolate reductase.Chemical science · 2016Article
- Pinpointing dynamic coupling in enzymes for efficient drug design.Future science OA · 2016Article
- The Effect of Protein Mass Modulation on Human Dihydrofolate Reductase.Biochemistry · 2016Article
- Transition state theory for enzyme kinetics.Archives of biochemistry and biophysics · 2015Review
- Are there dynamical effects in enzyme catalysis? Some thoughts concerning the enzymatic chemical step.Archives of biochemistry and biophysics · 2015Article
- Does the pressure dependence of kinetic isotope effects report usefully on dynamics in enzyme H-transfer reactions?The FEBS journal · 2015Review
- Chemical Ligation and Isotope Labeling to Locate Dynamic Effects during Catalysis by Dihydrofolate Reductase.Angewandte Chemie (International ed. in English) · 2015Article
- Network of remote and local protein dynamics in dihydrofolate reductase catalysis.ACS catalysis · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Isotopic substitution ((15)N, (13)C, (2)H) of a catalytically compromised variant of Escherichia coli dihydrofolate reductase, EcDHFR-N23PP/S148A, has been used to investigate the effect of these mutations on catalysis. The reduction of the rate constant of the chemical step in the EcDHFR-N23PP/S148A catalyzed reaction is essentially a consequence of an increase of the quasi-classical free energy barrier and to a minor extent of an increased number of recrossing trajectories on the transition state dividing surface. Since the variant enzyme is less well set up to catalyze the reaction, a higher degree of active site reorganization is needed to reach the TS. Although millisecond active site motions are lost in the variant, there is greater flexibility on the femtosecond time scale. The "dynamic knockout" EcDHFR-N23PP/S148A is therefore a "dynamic knock-in" at the level of the chemical step, and the increased dynamic coupling to the chemical coordinate is in fact detrimental to catalysis. This finding is most likely applicable not just to hydrogen transfer in EcDHFR but also to other enzymatic systems.
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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.