ArticleJournal of the American Chemical Society2010
Kinetic isotope effects for RNA cleavage by 2'-O- transphosphorylation: nucleophilic activation by specific base.
Article in Journal of the American Chemical Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Direct Competitive Kinetic Isotope Effect Measurement Using Quantitative Whole Molecule Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry.Chembiochem : a European journal of chemical biology · 2026Article
- Altered Mechanisms for Acid-Catalyzed RNA Cleavage and Isomerization Reactions Models.Journal of chemical theory and computation · 2023Article
- Dissociative Transition State in Hepatitis Delta Virus Ribozyme Catalysis.Journal of the American Chemical Society · 2023Article
- A general and efficient approach to synthesize the phosphoramidites of 5'-Nucleosides, nucleotides & nucleic acids · 2023Article
- Evidence That Nucleophile Deprotonation Exceeds Bond Formation in the HDV Ribozyme Transition State.Biochemistry · 2018Article
- Phosphodiester models for cleavage of nucleic acids.Beilstein journal of organic chemistry · 2018Review
- Investigation of the mechanism of the SpnF-catalyzed [4+2]-cycloaddition reaction in the biosynthesis of spinosyn A.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- A Multidimensional B-Spline Correction for Accurate Modeling Sugar Puckering in QM/MM Simulations.Journal of chemical theory and computation · 2017Article
- Experimental and Computational Evidence for a Loose Transition State in Phosphoroimidazolide Hydrolysis.Journal of the American Chemical Society · 2016Article
- Isotope effect analyses provide evidence for an altered transition state for RNA 2'-O-transphosphorylation catalyzed by Zn(2+).Chemical communications (Cambridge, England) · 2016Article
- A Two-Metal-Ion-Mediated Conformational Switching Pathway for HDV Ribozyme Activation.ACS catalysis · 2016Article
- Measuring specificity in multi-substrate/product systems as a tool to investigate selectivity in vivo.Biochimica et biophysica acta · 2016Review
- Effect of Zn2+ binding and enzyme active site on the transition state for RNA 2'-O-transphosphorylation interpreted through kinetic isotope effects.Biochimica et biophysica acta · 2015Article
- Heavy atom labeled nucleotides for measurement of kinetic isotope effects.Biochimica et biophysica acta · 2015Review
- Integration of kinetic isotope effect analyses to elucidate ribonuclease mechanism.Biochimica et biophysica acta · 2015Review
- Determination of hepatitis delta virus ribozyme N(-1) nucleobase and functional group specificity using internal competition kinetics.Analytical biochemistry · 2015Article
- Transition State Features in the Hepatitis Delta Virus Ribozyme Reaction Revealed by Atomic Perturbations.Journal of the American Chemical Society · 2015Article
- Determination of relative rate constants for in vitro RNA processing reactions by internal competition.Analytical biochemistry · 2014Article
- Mechanistic insights into RNA transphosphorylation from kinetic isotope effects and linear free energy relationships of model reactions.Chemistry (Weinheim an der Bergstrasse, Germany) · 2014Article
- Altered (transition) states: mechanisms of solution and enzyme catalyzed RNA 2'-O-transphosphorylation.Current opinion in chemical biology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
To better understand the interactions between catalysts and transition states during RNA strand cleavage, primary (18)O kinetic isotope effects (KIEs) and solvent D(2)O isotope effects were measured to probe the mechanism of base-catalyzed 2'-O-transphosphorylation of the RNA dinucleotide 5'-UpG-3'. The observed (18)O KIEs for the nucleophilic 2'-O and in the 5'-O leaving group at pH 14 are both large relative to reactions of phosphodiesters with good leaving groups, indicating that the reaction catalyzed by hydroxide has a transition state (TS) with advanced phosphorus-oxygen bond fission to the leaving group ((18)k(LG) = 1.034 +/- 0.004) and phosphorus-nucleophile bond formation ((18)k(NUC) = 0.984 +/- 0.004). A breakpoint in the pH dependence of the 2'-O-transphosphorylation rate to a pH independent phase above pH 13 has been attributed to the pK(a) of the 2'-OH nucleophile. A smaller nucleophile KIE is observed at pH 12 ((18)k(NUC) = 0.995 +/- 0.004) that is interpreted as the combined effect of the equilibrium isotope effect (ca. 1.02) on deprotonation of the 2'-hydroxyl nucleophile and the intrinsic KIE on the nucleophilic addition step (ca. 0.981). An alternative mechanism in which the hydroxide ion acts as a general base is considered unlikely given the lack of a solvent deuterium isotope effect above the breakpoint in the pH versus rate profile. These results represent the first direct analysis of the transition state for RNA strand cleavage. The primary (18)O KIE results and the lack of a kinetic solvent deuterium isotope effect together provide strong evidence for a late transition state and 2'-O nucleophile activation by specific base catalysis.
Indexed as
Identifiers
What OpenQuestion holds
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.