ArticleBiochemistry2015
Inverse thio effects in the hepatitis delta virus ribozyme reveal that the reaction pathway is controlled by metal ion charge density.
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- Simulations predict preferred MgBiophysical journal · 2024Article
- A ribozyme that uses lanthanides as cofactor.Nucleic acids research · 2023Article
- Dissociative Transition State in Hepatitis Delta Virus Ribozyme Catalysis.Journal of the American Chemical Society · 2023Article
- Graph deep learning locates magnesium ions in RNA.QRB discovery · 2022Article
- Synthesis of Oligoribonucleotides Containing a 2'-Amino-5'-The Journal of organic chemistry · 2021Article
- Single-pass transcription by T7 RNA polymerase.RNA (New York, N.Y.) · 2020Article
- In vitro Selection of Chemically Modified DNAzymes.ChemistryOpen · 2020Review
- 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
- From general base to general acid catalysis in a sodium-specific DNAzyme by a guanine-to-adenine mutation.Nucleic acids research · 2019Article
- Design of highly active double-pseudoknotted ribozymes: a combined computational and experimental study.Nucleic acids research · 2019Article
- Phosphorothioate DNA Mediated Sequence-Insensitive Etching and Ripening of Silver Nanoparticles.Frontiers in chemistry · 2019Article
- Evidence That Nucleophile Deprotonation Exceeds Bond Formation in the HDV Ribozyme Transition State.Biochemistry · 2018Article
- RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview.Chemical reviews · 2018Review
- Elucidation of Catalytic Strategies of Small Nucleolytic Ribozymes From Comparative Analysis of Active Sites.ACS catalysis · 2018Article
- Quantum mechanical force fields for condensed phase molecular simulations.Journal of physics. Condensed matter : an Institute of Physics journal · 2017Article
- Probing fast ribozyme reactions under biological conditions with rapid quench-flow kinetics.Methods (San Diego, Calif.) · 2017Article
- Understanding in-line probing experiments by modeling cleavage of nonreactive RNA nucleotides.RNA (New York, N.Y.) · 2017Article
- The GlcN6P cofactor plays multiple catalytic roles in the glmS ribozyme.Nature chemical biology · 2017Article
- Thermal Stability of RNA Structures with Bulky Cations in Mixed Aqueous Solutions.Biophysical journal · 2016Article
- Ambient-Potential Composite Ewald Method for ab Initio Quantum Mechanical/Molecular Mechanical Molecular Dynamics Simulation.Journal of chemical theory and computation · 2016Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The hepatitis delta virus (HDV) ribozyme self-cleaves in the presence of a wide range of monovalent and divalent ions. Prior theoretical studies provided evidence that self-cleavage proceeds via a concerted or stepwise pathway, with the outcome dictated by the valency of the metal ion. In the present study, we measure stereospecific thio effects at the nonbridging oxygens of the scissile phosphate under a wide range of experimental conditions, including varying concentrations of diverse monovalent and divalent ions, and combine these with quantum mechanical/molecular mechanical (QM/MM) free energy simulations on the stereospecific thio substrates. The RP substrate gives large normal thio effects in the presence of all monovalent ions. The SP substrate also gives normal or no thio effects, but only for smaller monovalent and divalent cations, such as Li(+), Mg(2+), Ca(2+), and Sr(2+); in contrast, sizable inverse thio effects are found for larger monovalent and divalent cations, including Na(+), K(+), NH4(+), and Ba(2+). Proton inventories are found to be unity in the presence of the larger monovalent and divalent ions, but two in the presence of Mg(2+). Additionally, rate-pH profiles are inverted for the low charge density ions, and only imidazole plus ammonium ions rescue an inactive C75Δ variant in the absence of Mg(2+). Results from the thio effect experiments, rate-pH profiles, proton inventories, and ammonium/imidazole rescue experiments, combined with QM/MM free energy simulations, support a change in the mechanism of HDV ribozyme self-cleavage from concerted and metal ion-stabilized to stepwise and proton transfer-stabilized as the charge density of the metal ion decreases.
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