ArticleBiochemistry2006
Effects of a distal mutation on active site chemistry.
Article in Biochemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 80 citations in OpenAlex.
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- Substrate Positioning Dynamics Involves a Non-Electrostatic Component to Mediate Catalysis.The journal of physical chemistry letters · 2023Article
- Allosteric regulatory control in dihydrofolate reductase is revealed by dynamic asymmetry.Protein science : a publication of the Protein Society · 2023Article
- Structural plasticity enables evolution and innovation of RuBisCO assemblies.Science advances · 2022Article
- Temperature-Dependent Kinetic Isotope Effects in R67 Dihydrofolate Reductase from Path-Integral Simulations.The journal of physical chemistry. B · 2021Article
- Recent advances suggest increased influence of selective pressure in allostery.Current opinion in structural biology · 2020Review
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- Conformational Dynamics and Allosteric Regulation Landscapes of Germline PTEN Mutations Associated with Autism Compared to Those Associated with Cancer.American journal of human genetics · 2019Article
- A Biophysical Perspective on Enzyme Catalysis.Biochemistry · 2019Article
- Modulation of allosteric coupling by mutations: from protein dynamics and packing to altered native ensembles and function.Current opinion in structural biology · 2019Review
- 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
- Benchmarking Quantum Mechanics/Molecular Mechanics (QM/MM) Methods on the Thymidylate Synthase-Catalyzed Hydride Transfer.Journal of chemical theory and computation · 2017Article
- Examinations of the Chemical Step in Enzyme Catalysis.Methods in enzymology · 2016Article
- Perturbation of the Conformational Dynamics of an Active-Site Loop Alters Enzyme Activity.Structure (London, England : 1993) · 2015Article
- 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
- Linking protein motion to enzyme catalysis.Molecules (Basel, Switzerland) · 2015Review
- Article
- Different dynamical effects in mesophilic and hyperthermophilic dihydrofolate reductases.Journal of the American Chemical Society · 2014Article
- How Accurate Are Transition States from Simulations of Enzymatic Reactions?Journal of chemical theory and computation · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Previous studies of Escherichia coli dihydrofolate reductase (ecDHFR) have demonstrated that residue G121, which is 19 A from the catalytic center, is involved in catalysis, and long distance dynamical motions were implied. Specifically, the ecDHFR mutant G121V has been extensively studied by various experimental and theoretical tools, and the mutation's effect on kinetic, structural, and dynamical features of the enzyme has been explored. This work examined the effect of this mutation on the physical nature of the catalyzed hydride transfer step by means of intrinsic kinetic isotope effects (KIEs), their temperature dependence, and activation parameters as described previously for wild type ecDHFR [Sikorski, R. S., et al. (2004) J. Am. Chem. Soc. 126, 4778-4779]. The temperature dependence of initial velocities was used to estimate activation parameters. Isotope effects on the preexponential Arrhenius factors, and the activation energy, could be rationalized by an environmentally coupled hydrogen tunneling model, similar to the one used for the wild-type enzyme. Yet, in contrast to that in the wild type, fluctuations of the donor-acceptor distance were now required. Secondary (2 degrees ) KIEs were also measured for both H- and D-transfer, and as in the case of the wild-type enzyme, no coupled motion was detected. Despite these similarities, the reduced rates, the slightly inflated primary (1 degrees ) KIEs, and their temperature dependence, together with relatively deflated 2 degrees KIEs, indicate that the potential surface prearrangement was not as ideal as for the wild-type enzyme. These findings support theoretical studies suggesting that the G121V mutation led to a different conformational ensemble of reactive states and less effective rearrangement of the potential surface but has an only weak effect on H-tunneling.
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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.