ArticleBiochemistry2015
Two Divalent Metal Ions and Conformational Changes Play Roles in the Hammerhead Ribozyme Cleavage Reaction.
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 68 citations in OpenAlex.
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- Cat_Wiz: a stereochemistry-guided toolkit for locating, diagnosing, and annotating Mg2+ ions in RNA structures.Nucleic acids research · 2026Article
- A minimal RNA-cleaving DNAzyme and its catalytic mechanism.Nucleic acids research · 2026Article
- Enhanced hammerhead ribozyme turnover rates: Reevaluating therapeutic space for small catalytic RNAs.Molecular therapy. Nucleic acids · 2025Article
- A hammerhead ribozyme selects mechanically stable conformations for catalysis against viral RNA.Communications biology · 2025Article
- The structure and catalytic mechanism of a pseudoknot-containing hammerhead ribozyme.Nature communications · 2024Article
- The 8-17 DNAzyme can operate in a single active structure regardless of metal ion cofactor.Nature communications · 2024Article
- When will RNA get its AlphaFold moment?Nucleic acids research · 2023Article
- Rapid Kinetics of Pistol Ribozyme: Insights into Limits to RNA Catalysis.Biochemistry · 2023Article
- Rock, scissors, paper: How RNA structure informs function.The Plant cell · 2023Article
- Structural variants and modifications of hammerhead ribozymes targeting influenza A virus conserved structural motifs.Molecular therapy. Nucleic acids · 2022Article
- RNA Electrostatics: How Ribozymes Engineer Active Sites to Enable Catalysis.The journal of physical chemistry. B · 2022Article
- Article
- Self-cleaving ribozymes: substrate specificity and synthetic biology applications.RSC chemical biology · 2021Review
- FARFAR2: Improved De Novo Rosetta Prediction of Complex Global RNA Folds.Structure (London, England : 1993) · 2020Article
- Single Mutation in Hammerhead Ribozyme Favors Cleavage Activity with Manganese over Magnesium.Non-coding RNA · 2020Article
- An Evolutionary Trace method defines functionally important bases and sites common to RNA families.PLoS computational biology · 2020Article
- The L-platform/L-scaffold framework: a blueprint for RNA-cleaving nucleic acid enzyme design.RNA (New York, N.Y.) · 2020Article
- Confluence of theory and experiment reveals the catalytic mechanism of the Varkud satellite ribozyme.Nature chemistry · 2020Article
- Dynamical ensemble of the active state and transition state mimic for the RNA-cleaving 8-17 DNAzyme in solution.Nucleic acids research · 2019Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The hammerhead ribozyme is a self-cleaving RNA broadly dispersed across all kingdoms of life. Although it was the first of the small, nucleolytic ribozymes discovered, the mechanism by which it catalyzes its reaction remains elusive. The nucleobase of G12 is well positioned to be a general base, but it is unclear if or how this guanine base becomes activated for proton transfer. Metal ions have been implicated in the chemical mechanism, but no interactions between divalent metal ions and the cleavage site have been observed crystallographically. To better understand how this ribozyme functions, we have solved crystal structures of wild-type and G12A mutant ribozymes. We observe a pH-dependent conformational change centered around G12, consistent with this nucleotide becoming deprotonated. Crystallographic and kinetic analysis of the G12A mutant reveals a Zn(2+) specificity switch suggesting a direct interaction between a divalent metal ion and the purine at position 12. The metal ion specificity switch and the pH-rate profile of the G12A mutant suggest that the minor imino tautomer of A12 serves as the general base in the mutant ribozyme. We propose a model in which the hammerhead ribozyme rearranges prior to the cleavage reaction, positioning two divalent metal ions in the process. The first metal ion, positioned near G12, becomes directly coordinated to the O6 keto oxygen, to lower the pKa of the general base and organize the active site. The second metal ion, positioned near G10.1, bridges the N7 of G10.1 and the scissile phosphate and may participate directly in the cleavage reaction.
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