ArticleBiochemistry2016
Hydride Transfer in DHFR by Transition Path Sampling, Kinetic Isotope Effects, and Heavy Enzyme Studies.
Article in Biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Mutexa: A Computational Ecosystem for Intelligent Protein Engineering.Journal of chemical theory and computation · 2023Review
- Protein Dynamics and Enzymatic Catalysis.The journal of physical chemistry. B · 2023Review
- Perspective: Path Sampling Methods Applied to Enzymatic Catalysis.Journal of chemical theory and computation · 2022Review
- Comparison of the Role of Protein Dynamics in Catalysis by Dihydrofolate Reductase fromThe journal of physical chemistry. B · 2022Article
- Hydride Transfer Mechanism of Enzymatic Sugar Nucleotide C2 Epimerization Probed with a Loose-Fit CDP-Glucose Substrate.ACS catalysis · 2022Article
- 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
- Site-Specific Tryptophan Labels Reveal Local Microsecond-Millisecond Motions of Dihydrofolate Reductase.Molecules (Basel, Switzerland) · 2020Article
- Biosynthetic Incorporation of Site-Specific Isotopes in β-Lactam Antibiotics Enables Biophysical Studies.ACS chemical biology · 2020Article
- Heavy Enzymes and the Rational Redesign of Protein Catalysts.Chembiochem : a European journal of chemical biology · 2019Article
- Article
- Tripping the light fantastic in membrane redox biology: linking dynamic structures to function in ER electron transfer chains.The FEBS journal · 2019Review
- Article
- Promoting Vibrations and the Function of Enzymes. Emerging Theoretical and Experimental Convergence.Biochemistry · 2018Review
- Origins of Enzyme Catalysis: Experimental Findings for C-H Activation, New Models, and Their Relevance to Prevailing Theoretical Constructs.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
- Catalytic-site design for inverse heavy-enzyme isotope effects in human purine nucleoside phosphorylase.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Triple Isotope Effects Support Concerted Hydride and Proton Transfer and Promoting Vibrations in Human Heart Lactate Dehydrogenase.Journal of the American Chemical Society · 2016Article
- Modulating Enzyme Catalysis through Mutations Designed to Alter Rapid Protein Dynamics.Journal of the American Chemical Society · 2016Article
- The Effect of Protein Mass Modulation on Human Dihydrofolate Reductase.Biochemistry · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Escherichia coli dihydrofolate reductase (ecDHFR) is used to study fundamental principles of enzyme catalysis. It remains controversial whether fast protein motions are coupled to the hydride transfer catalyzed by ecDHFR. Previous studies with heavy ecDHFR proteins labeled with (13)C, (15)N, and nonexchangeable (2)H reported enzyme mass-dependent hydride transfer kinetics for ecDHFR. Here, we report refined experimental and computational studies to establish that hydride transfer is independent of protein mass. Instead, we found the rate constant for substrate dissociation to be faster for heavy DHFR. Previously reported kinetic differences between light and heavy DHFRs likely arise from kinetic steps other than the chemical step. This study confirms that fast (femtosecond to picosecond) protein motions in ecDHFR are not coupled to hydride transfer and provides an integrative computational and experimental approach to resolve fast dynamics coupled to chemical steps in enzyme catalysis.
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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.