ArticleProceedings of the National Academy of Sciences of the United States of America2007
Evidence for proton transfer in the rate-limiting step of a fast-cleaving Varkud satellite ribozyme.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Beyond the Plateau: pL Dependence of Proton Inventories as a Tool for Studying Ribozyme and Ribonuclease Catalysis.Biochemistry · 2021Article
- Confluence of theory and experiment reveals the catalytic mechanism of the Varkud satellite ribozyme.Nature chemistry · 2020Article
- The L-platform/L-scaffold framework: a blueprint for RNA-cleaving nucleic acid enzyme design.RNA (New York, N.Y.) · 2020Article
- Insights into RNA structure and dynamics from recent NMR and X-ray studies of the Neurospora Varkud satellite ribozyme.Wiley interdisciplinary reviews. RNA · 2017Review
- Rational engineering of the Neurospora VS ribozyme to allow substrate recognition via different kissing-loop interactions.Nucleic acids research · 2016Article
- Structure of a prereaction complex between the nerve agent sarin, its biological target acetylcholinesterase, and the antidote HI-6.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The NMR structure of the II-III-VI three-way junction from the Neurospora VS ribozyme reveals a critical tertiary interaction and provides new insights into the global ribozyme structure.RNA (New York, N.Y.) · 2015Article
- Solvent and Temperature Probes of the Long-Range Electron-Transfer Step in Tyramine β-Monooxygenase: Demonstration of a Long-Range Proton-Coupled Electron-Transfer Mechanism.Journal of the American Chemical Society · 2015Article
- A remarkably stable kissing-loop interaction defines substrate recognition by the Neurospora Varkud Satellite ribozyme.RNA (New York, N.Y.) · 2014Article
- Nucleic acid catalysis: metals, nucleobases, and other cofactors.Chemical reviews · 2014Review
- NMR localization of divalent cations at the active site of the Neurospora VS ribozyme provides insights into RNA-metal-ion interactions.Biochemistry · 2014Article
- Helix-length compensation studies reveal the adaptability of the VS ribozyme architecture.Nucleic acids research · 2012Article
- Mechanisms of RNA catalysis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2011Article
- Additional roles of a peripheral loop-loop interaction in the Neurospora VS ribozyme.Nucleic acids research · 2011Article
- NMR structure of the A730 loop of the Neurospora VS ribozyme: insights into the formation of the active site.Nucleic acids research · 2011Article
- Do the hairpin and VS ribozymes share a common catalytic mechanism based on general acid-base catalysis? A critical assessment of available experimental data.RNA (New York, N.Y.) · 2011Article
- Nucleobase-mediated general acid-base catalysis in the Varkud satellite ribozyme.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Catalytic importance of a protonated adenosine in the hairpin ribozyme active site.Biochemistry · 2010Article
- Identification of catalytic metal ion ligands in ribozymes.Methods (San Diego, Calif.) · 2009Review
- Formation of an active site in trans by interaction of two complete Varkud Satellite ribozymes.RNA (New York, N.Y.) · 2009Article
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2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A fast-cleaving version of the Varkud satellite ribozyme, called RG, shows an apparent cis-cleavage rate constant of 5 sec(-1), similar to the rates of protein enzymes that catalyze similar reactions. Here, we describe mutational, pH-rate, and kinetic solvent isotope experiments that investigate the identity and rate constant of the rate-limiting step in this reaction. Self-cleavage of RG exhibits a bell-shaped rate vs. pH profile with apparent pK(a)s of 5.8 and 8.3, consistent with the protonation state of two nucleotides being important for the rate of cleavage. Cleavage experiments in heavy water (D(2)O) revealed a kinetic solvent isotope effect consistent with proton transfer in the rate-limiting step. A mutant RNA that disrupts a peripheral loop-loop interaction involved in RNA folding exhibits pH- and D(2)O-independent cleavage approximately 10(3)-fold slower than wild type, suggesting that this mutant is limited by a different step than wild type. Substitution of adenosine 756 in the putative active-site loop with cytosine also decreases the cleavage rate approximately 10(3)-fold, but the A756C mutant retains pH- and D(2)O-sensitivity similar to wild type, consistent with this mutant and wild type being limited by the chemical step of the reaction. These results suggest that the RG ribozyme provides a good experimental system to investigate the nature of fast, rate-limiting steps in a ribozyme cleavage reaction.
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