ArticleProceedings of the National Academy of Sciences of the United States of America2011
Femtosecond dynamics coupled to chemical barrier crossing in a Born-Oppenheimer enzyme.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed.
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- Mechanistic Insights into GTP Hydrolysis by the RhoA Protein: Catalytic Impact of Glutamine Tautomerism.ACS catalysis · 2025Article
- Allosteric activation unveils protein-mass modulation of ATP phosphoribosyltransferase product release.Communications chemistry · 2024Article
- Decreased Transition-State Analogue Affinity in Isotopically Heavy MTAN with Increased Catalysis.Biochemistry · 2023Article
- Protein Dynamics and Enzymatic Catalysis.The journal of physical chemistry. B · 2023Review
- Protein dynamics: The future is bright and complicated!Structural dynamics (Melville, N.Y.) · 2023Article
- Atomistic description of the relationship between protein dynamics and catalysis with transition path sampling.Methods in enzymology · 2023Review
- Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation.Nature communications · 2022Article
- 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
- Inverse heavy enzyme isotope effects in methylthioadenosine nucleosidases.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cryo-kinetics Reveal Dynamic Effects on the Chemistry of Human Dihydrofolate Reductase.Chembiochem : a European journal of chemical biology · 2021Article
- Protein Mass-Modulated Effects in Alkaline Phosphatase.Biochemistry · 2021Article
- Role of Protein Motions in Catalysis by Formate Dehydrogenase.The journal of physical chemistry. B · 2020Article
- The Energetic Origin of Different Catalytic Activities in Temperature-Adapted Trypsins.ACS omega · 2020Article
- Oscillatory Active-site Motions Correlate with Kinetic Isotope Effects in Formate Dehydrogenase.ACS catalysis · 2019Article
- Effect of Protein Isotope Labeling on the Catalytic Mechanism of Lactate Dehydrogenase.The journal of physical chemistry. B · 2019Article
13 more citing papers are in PubMed but not listed here.
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3 authors.
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Abstract
Contributions of fast (femtosecond) dynamic motion to barrier crossing at enzyme catalytic sites is in dispute. Human purine nucleoside phosphorylase (PNP) forms a ribocation-like transition state in the phosphorolysis of purine nucleosides and fast protein motions have been proposed to participate in barrier crossing. In the present study, (13)C-, (15)N-, (2)H-labeled human PNP (heavy PNP) was expressed, purified to homogeneity, and shown to exhibit a 9.9% increase in molecular mass relative to its unlabeled counterpart (light PNP). Kinetic isotope effects and steady-state kinetic parameters were indistinguishable for both enzymes, indicating that transition-state structure, equilibrium binding steps, and the rate of product release were not affected by increased protein mass. Single-turnover rate constants were slowed for heavy PNP, demonstrating reduced probability of chemical barrier crossing from enzyme-bound substrates to enzyme-bound products. In a second, independent method to probe barrier crossing, heavy PNP exhibited decreased forward commitment factors, also revealing mass-dependent decreased probability for barrier crossing. Increased atomic mass in human PNP alters bond vibrational modes on the femtosecond time scale and reduces on-enzyme chemical barrier crossing. This study demonstrates coupling of enzymatic bond vibrations on the femtosecond time scale to barrier crossing.
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