ArticleThe journal of physical chemistry. B2015
Evolution alters the enzymatic reaction coordinate of dihydrofolate reductase.
Article in The journal of physical chemistry. B, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Considering Metabolic Context in Enzyme Evolution and Design.Biochemistry · 2025Review
- 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
- Convergence in determining enzyme functional descriptors across Kemp eliminase variants.Electronic structure (Bristol, England) · 2022Article
- Comparison of the Role of Protein Dynamics in Catalysis by Dihydrofolate Reductase fromThe journal of physical chemistry. B · 2022Article
- Cryo-kinetics Reveal Dynamic Effects on the Chemistry of Human Dihydrofolate Reductase.Chembiochem : a European journal of chemical biology · 2021Article
- Multiple Reaction Pathways in the Morphinone Reductase-Catalyzed Hydride Transfer Reaction.ACS omega · 2020Article
- Harnessing Conformational Plasticity to Generate Designer Enzymes.Journal of the American Chemical Society · 2020Review
- The polymorphism of rs11614913 T/T in pri-American journal of translational research · 2020Article
- Article
- Convergence of theory and experiment on the role of preorganization, quantum tunneling and enzyme motions into flavoenzyme-catalyzed hydride transfer.ACS catalysis · 2019Article
- Directed Evolution as a Probe of Rate Promoting Vibrations Introduced via Mutational Change.Biochemistry · 2018Article
- Quantifying the limits of transition state theory in enzymatic catalysis.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Structurally Linked Dynamics in Lactate Dehydrogenases of Evolutionarily Distinct Species.Biochemistry · 2017Article
- Structure-based analysis of Bacilli and plasmid dihydrofolate reductase evolution.Journal of molecular graphics & modelling · 2017Article
- The Effect of Protein Mass Modulation on Human Dihydrofolate Reductase.Biochemistry · 2016Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
How evolution has affected enzyme function is a topic of great interest in the field of biophysical chemistry. Evolutionary changes from Escherichia coli dihydrofolate reductase (ecDHFR) to human dihydrofolate reductase (hsDHFR) have resulted in increased catalytic efficiency and an altered dynamic landscape in the human enzyme. Here, we show that a subpicosecond protein motion is dynamically coupled to hydride transfer catalyzed by hsDHFR but not ecDHFR. This motion propagates through residues that correspond to mutational events along the evolutionary path from ecDHFR to hsDHFR. We observe an increase in the variability of the transition states, reactive conformations, and times of barrier crossing in the human system. In the hsDHFR active site, we detect structural changes that have enabled the coupling of fast protein dynamics to the reaction coordinate. These results indicate a shift in the DHFR family to a form of catalysis that incorporates rapid protein dynamics and a concomitant shift to a more flexible path through reactive phase space.
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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.