ArticleRNA (New York, N.Y.)2012
Ground-state coordination of a catalytic metal to the scissile phosphate of a tertiary-stabilized Hammerhead ribozyme.
Article in RNA (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Rapid Kinetics of Pistol Ribozyme: Insights into Limits to RNA Catalysis.Biochemistry · 2023Article
- The L-platform/L-scaffold framework: a blueprint for RNA-cleaving nucleic acid enzyme design.RNA (New York, N.Y.) · 2020Article
- Dynamical ensemble of the active state and transition state mimic for the RNA-cleaving 8-17 DNAzyme in solution.Nucleic acids research · 2019Article
- Molecular simulations of the pistol ribozyme: unifying the interpretation of experimental data and establishing functional links with the hammerhead ribozyme.RNA (New York, N.Y.) · 2019Article
- Divalent Metal Ion Activation of a Guanine General Base in the Hammerhead Ribozyme: Insights from Molecular Simulations.Biochemistry · 2017Article
- Probing fast ribozyme reactions under biological conditions with rapid quench-flow kinetics.Methods (San Diego, Calif.) · 2017Article
- The GlcN6P cofactor plays multiple catalytic roles in the glmS ribozyme.Nature chemical biology · 2017Article
- Two Active Site Divalent Ions in the Crystal Structure of the Hammerhead Ribozyme Bound to a Transition State Analogue.Biochemistry · 2016Article
- An active site rearrangement within the Tetrahymena group I ribozyme releases nonproductive interactions and allows formation of catalytic interactions.RNA (New York, N.Y.) · 2016Article
- Force Field for Mg(2+), Mn(2+), Zn(2+), and Cd(2+) Ions That Have Balanced Interactions with Nucleic Acids.The journal of physical chemistry. B · 2015Article
- Two Divalent Metal Ions and Conformational Changes Play Roles in the Hammerhead Ribozyme Cleavage Reaction.Biochemistry · 2015Article
- Dynamic nuclear polarization of nucleic acid with endogenously bound manganese.Journal of biomolecular NMR · 2015Article
- 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
- Active-site monovalent cations revealed in a 1.55-Å-resolution hammerhead ribozyme structure.Journal of molecular biology · 2013Article
- Thio effects and an unconventional metal ion rescue in the genomic hepatitis delta virus ribozyme.Biochemistry · 2013Article
- Bridging the gap between theory and experiment to derive a detailed understanding of hammerhead ribozyme catalysis.Progress in molecular biology and translational science · 2013Review
- RNA folding and catalysis mediated by iron (II).PloS one · 2012Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Although the Hammerhead ribozyme (HHRz) has long been used as a model system in the field of ribozyme enzymology, several details of its mechanism are still not well understood. In particular, significant questions remain concerning the disposition and role of catalytic metals in the HHRz. Previous metal-rescue experiments using a "minimal" HHRz resulted in prediction of a catalytic metal that is bound in the A9/G10.1 site in the ground state of the reaction and that bridges to the scissile phosphate further along the reaction pathway. "Native" or extended HHRz constructs contain tertiary contacts that stabilize a more compact structure at moderate ionic strength. We performed Cd(2+) rescue experiments on an extended HHRz from Schistosoma mansoni using stereo-pure scissile phosphorothioate-substituted substrates in order to determine whether a metal ion makes contact with the scissile phosphate in the ground state or further along the reaction coordinate. Inhibition in Ca(2+)/Mg(2+) and rescue by thiophilic Cd(2+) was specific for the R(p)-S stereoisomer of the scissile phosphate. The affinity of the rescuing Cd(2+), measured in two different ionic strength backgrounds, increased fourfold to 17-fold when the pro-R(p) oxygen is replaced by sulfur. These data support a model in which the rescuing metal ion makes a ground-state interaction with the scissile phosphate in the native HHRz. The resulting model for Mg(2+) activation in the HHRz places a metal ion in contact with the scissile phosphate, where it may provide ground-state electrostatic activation of the substrate.
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