ArticleBiochemistry2009
A catalytic metal ion interacts with the cleavage Site G.U wobble in the HDV ribozyme.
Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Structure and mechanism of HDV ribozymes revealing Lewis acid catalysis by a metal ion.Nature communications · 2026Article
- Dissociative Transition State in Hepatitis Delta Virus Ribozyme Catalysis.Journal of the American Chemical Society · 2023Article
- Review
- Dynamical ensemble of the active state and transition state mimic for the RNA-cleaving 8-17 DNAzyme in solution.Nucleic acids research · 2019Article
- Evidence That Nucleophile Deprotonation Exceeds Bond Formation in the HDV Ribozyme Transition State.Biochemistry · 2018Article
- Studying metal ion binding properties of a three-way junction RNA by heteronuclear NMR.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2016Article
- A Two-Metal-Ion-Mediated Conformational Switching Pathway for HDV Ribozyme Activation.ACS catalysis · 2016Article
- Assessment of metal-assisted nucleophile activation in the hepatitis delta virus ribozyme from molecular simulation and 3D-RISM.RNA (New York, N.Y.) · 2015Article
- Wobble pairs of the HDV ribozyme play specific roles in stabilization of active site dynamics.Physical chemistry chemical physics : PCCP · 2015Article
- Multiscale methods for computational RNA enzymology.Methods in enzymology · 2015Article
- Disparate HDV ribozyme crystal structures represent intermediates on a rugged free-energy landscape.RNA (New York, N.Y.) · 2014Article
- NMR localization of divalent cations at the active site of the Neurospora VS ribozyme provides insights into RNA-metal-ion interactions.Biochemistry · 2014Article
- Thio effects and an unconventional metal ion rescue in the genomic hepatitis delta virus ribozyme.Biochemistry · 2013Article
- Article
- Testing the nearest neighbor model for canonical RNA base pairs: revision of GU parameters.Biochemistry · 2012Article
- Characterization of the trans Watson-Crick GU base pair located in the catalytic core of the antigenomic HDV ribozyme.PloS one · 2012Article
- Quantum Mechanical/Molecular Mechanical Study of the HDV Ribozyme: Impact of the Catalytic Metal Ion on the Mechanism.The journal of physical chemistry letters · 2011Article
- Two distinct catalytic strategies in the hepatitis δ virus ribozyme cleavage reaction.Biochemistry · 2011Review
- Characterization of the Structure and Dynamics of the HDV Ribozyme at Different Stages Along the Reaction Path.The journal of physical chemistry letters · 2011Article
- Identification of an hepatitis delta virus-like ribozyme at the mRNA 5'-end of the L1Tc retrotransposon from Trypanosoma cruzi.Nucleic acids research · 2011Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The HDV ribozyme self-cleaves by a chemical mechanism involving general acid-base catalysis to generate 2',3'-cyclic phosphate and 5'-hydroxyl termini. Biochemical studies from several laboratories have implicated C75 as the general acid and hydrated magnesium as the general base. We have previously shown that C75 has a pK(a) shifted >2 pH units toward neutrality [Gong, B., Chen, J. H., Chase, E., Chadalavada, D. M., Yajima, R., Golden, B. L., Bevilacqua, P. C., and Carey, P. R. (2007) J. Am. Chem. Soc. 129, 13335-13342], while in crystal structures, it is well-positioned for proton transfer. However, no evidence for a hydrated magnesium poised to serve as a general base in the reaction has been observed in high-resolution crystal structures of various reaction states and mutants. Herein, we use solution kinetic experiments and parallel Raman crystallographic studies to examine the effects of pH on the rate and Mg(2+) binding properties of wild-type and 7-deazaguanosine mutants of the HDV ribozyme. These data suggest that a previously unobserved hydrated magnesium ion interacts with N7 of the cleavage site G.U wobble base pair. Integrating this metal ion binding site with the available crystal structures provides a new three-dimensional model for the active site of the ribozyme that accommodates all available biochemical data and appears competent for catalysis. The position of this metal is consistent with a role of a magnesium-bound hydroxide as a general base as dictated by biochemical data.
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