ArticleJournal of the American Chemical Society2011
The role of large-scale motions in catalysis by dihydrofolate reductase.
Article in Journal of the American Chemical Society, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 44 citations in OpenAlex.
- X-ray-driven chemistry and conformational heterogeneity in atomic resolution crystal structures of bacterial dihydrofolate reductases.bioRxiv : the preprint server for biology · 2023Article
- The Mystery of Piezophiles: Understudied Microorganisms from the Deep, Dark Subsurface.Microorganisms · 2023Review
- 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
- Why are some Enzymes Dimers? Flexibility and Catalysis inACS catalysis · 2019Article
- Consensus sequence design as a general strategy to create hyperstable, biologically active proteins.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Biophysical Characterization of a Disabled Double Mutant of Soybean Lipoxygenase: The "Undoing" of Precise Substrate Positioning Relative to Metal Cofactor and an Identified Dynamical Network.Journal of the American Chemical Society · 2019Article
- Enzymes from piezophiles.Seminars in cell & developmental biology · 2018Review
- Why the Energy Landscape of Barnase Is Hierarchical.Frontiers in molecular biosciences · 2018Article
- Benchmarking Quantum Mechanics/Molecular Mechanics (QM/MM) Methods on the Thymidylate Synthase-Catalyzed Hydride Transfer.Journal of chemical theory and computation · 2017Article
- Minimization of dynamic effects in the evolution of dihydrofolate reductase.Chemical science · 2016Article
- Are there dynamical effects in enzyme catalysis? Some thoughts concerning the enzymatic chemical step.Archives of biochemistry and biophysics · 2015Article
- Different dynamical effects in mesophilic and hyperthermophilic dihydrofolate reductases.Journal of the American Chemical Society · 2014Article
- Thermal adaptation of dihydrofolate reductase from the moderate thermophile Geobacillus stearothermophilus.Biochemistry · 2014Article
- Increased dynamic effects in a catalytically compromised variant of Escherichia coli dihydrofolate reductase.Journal of the American Chemical Society · 2013Article
- Unraveling the role of protein dynamics in dihydrofolate reductase catalysis.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Direct observation of T4 lysozyme hinge-bending motion by fluorescence correlation spectroscopy.Biophysical journal · 2012Article
- Evidence that a 'dynamic knockout' in Escherichia coli dihydrofolate reductase does not affect the chemical step of catalysis.Nature chemistry · 2012Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Dihydrofolate reductase has long been used as a model system to study the coupling of protein motions to enzymatic hydride transfer. By studying environmental effects on hydride transfer in dihydrofolate reductase (DHFR) from the cold-adapted bacterium Moritella profunda (MpDHFR) and comparing the flexibility of this enzyme to that of DHFR from Escherichia coli (EcDHFR), we demonstrate that factors that affect large-scale (i.e., long-range, but not necessarily large amplitude) protein motions have no effect on the kinetic isotope effect on hydride transfer or its temperature dependence, although the rates of the catalyzed reaction are affected. Hydrogen/deuterium exchange studies by NMR-spectroscopy show that MpDHFR is a more flexible enzyme than EcDHFR. NMR experiments with EcDHFR in the presence of cosolvents suggest differences in the conformational ensemble of the enzyme. The fact that enzymes from different environmental niches and with different flexibilities display the same behavior of the kinetic isotope effect on hydride transfer strongly suggests that, while protein motions are important to generate the reaction ready conformation, an optimal conformation with the correct electrostatics and geometry for the reaction to occur, they do not influence the nature of the chemical step itself; large-scale motions do not couple directly to hydride transfer proper in DHFR.
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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.