ArticleJournal of the American Chemical Society2009
Direct Raman measurement of an elevated base pKa in the active site of a small ribozyme in a precatalytic conformation.
Article in Journal of the American Chemical Society, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Two Divalent Metal Ions and Conformational Changes Play Roles in the Hammerhead Ribozyme Cleavage Reaction.Biochemistry · 2015Article
- Inverse thio effects in the hepatitis delta virus ribozyme reveal that the reaction pathway is controlled by metal ion charge density.Biochemistry · 2015Article
- Molecular targets of aspirin and cancer prevention.British journal of cancer · 2014Review
- Evidence for the role of active site residues in the hairpin ribozyme from molecular simulations along the reaction path.Journal of the American Chemical Society · 2014Article
- Quantum mechanical/molecular mechanical free energy simulations of the self-cleavage reaction in the hepatitis delta virus ribozyme.Journal of the American Chemical Society · 2014Article
- Direct observation of multiple tautomers of oxythiamine and their recognition by the thiamine pyrophosphate riboswitch.ACS chemical biology · 2014Article
- Experimental approaches for measuring pKa's in RNA and DNA.Methods in enzymology · 2014Article
- Towards Accurate Prediction of Protonation Equilibrium of Nucleic Acids.The journal of physical chemistry letters · 2013Article
- Intermolecular domain docking in the hairpin ribozyme: metal dependence, binding kinetics and catalysis.RNA biology · 2013Article
- pH-dependent dynamics of complex RNA macromolecules.Journal of chemical theory and computation · 2013Article
- Article
- A transition-state interaction shifts nucleobase ionization toward neutrality to facilitate small ribozyme catalysis.Journal of the American Chemical Society · 2012Article
- General acid-base catalysis mediated by nucleobases in the hairpin ribozyme.Journal of the American Chemical Society · 2012Article
- Constant pH Molecular Dynamics Simulations of Nucleic Acids in Explicit Solvent.Journal of chemical theory and computation · 2012Article
- Charged nucleobases and their potential for RNA catalysis.Accounts of chemical research · 2011Article
- QM/MM studies of hairpin ribozyme self-cleavage suggest the feasibility of multiple competing reaction mechanisms.The journal of physical chemistry. B · 2011Article
- Two distinct catalytic strategies in the hepatitis δ virus ribozyme cleavage reaction.Biochemistry · 2011Review
- Use of a coenzyme by the glmS ribozyme-riboswitch suggests primordial expansion of RNA chemistry by small molecules.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2011Article
- The glmS ribozyme tunes the catalytically critical pK(a) of its coenzyme glucosamine-6-phosphate.Journal of the American Chemical Society · 2011Article
- glmS Riboswitch binding to the glucosamine-6-phosphate α-anomer shifts the pKa toward neutrality.Biochemistry · 2011Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Catalytic RNA molecules can achieve rate acceleration by shifting base pK(a) values toward neutrality. Prior evidence has suggested that base A38 of the hairpin ribozyme plays an important role in phosphoryl transfer, possibly functioning as a general acid, or by orienting a specific water molecule for proton transfer. To address the role of A38, we used Raman spectroscopy to measure directly the pK(a) of the N1-imino moiety in the context of hairpin ribozyme crystals representative of a "precatalytic" conformation. The results revealed that the pK(a) of A38 is shifted to 5.46 +/- 0.05 relative to 3.68 +/- 0.06 derived from a reference solution of the nucleotide AMP. The elevated pK(a) correlates well with the first titration point of the macroscopic pH-rate profile of the hairpin ribozyme in solution and strongly supports A38 as a general acid catalyst in bond scission. The results confirm that A38 is protonated before the transition state, which would promote phosphorane development. Overall, the results establish a cogent structure-function paradigm that expands our understanding of how RNA structure can enhance nucleobase reactivity to catalyze biological reactions.
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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.