RNA · 2006 · 66 citations · 22 references
PharmacyBiochemistryMolecular BiologyCatalysisNucleic Acid ChemistryRna ProcessingEnzyme KineticsNucleic Acid CleavageNucleobase ChemistryRibonucleic Acid (Rna) ChemistryRna ChemistryRna CleavageCatalytic Acid-base CatalysisGeneral Acid CatalysisGeneral Acid-base CatalysisHairpin Ribozyme CleavageHairpin RibozymesLigation KineticsRibozyme-mediated CleavageRibozymes
RNA catalysis is important in the processing and translation of RNA molecules, yet the mechanisms of catalysis are still unclear in most cases. We have studied the role of nucleobase catalysis in the hairpin ribozyme, where the scissile phosphate is juxtaposed between guanine and adenine bases. We show that a modified ribozyme in which guanine 8 has been substituted by an imidazole base is active in both cleavage and ligation, with ligation rates 10-fold faster than cleavage. The rates of both reactions exhibit bell-shaped dependence on pH, with pK(a) values of 5.7 +/- 0.1 and 7.7 +/- 0.1 for cleavage and 6.1 +/- 0.3 and 6.9 +/- 0.3 for ligation. The data provide good evidence for general acid-base catalysis by the nucleobases.
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Transition State Stabilization by a Catalytic RNA
Peter B. Rupert, Archna P. Massey, Snorri Th. Sigurdsson et al. · Science · 2002 · 286 citations
A conformational switch controls hepatitis delta virus ribozyme catalysis
Ailong Ke, Kaihong Zhou, Fang Ding et al. · Nature · 2004 · 279 citations