ArticleRNA (New York, N.Y.)2009
Molecular dynamics suggest multifunctionality of an adenine imino group in acid-base catalysis of the hairpin ribozyme.
Article in RNA (New York, N.Y.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Critical structural perturbations of ribozyme active sites induced by 2'-O-methylation commonly used in structural studies.Nucleic acids research · 2026Article
- RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview.Chemical reviews · 2018Review
- Thermodynamics and kinetics of RNA tertiary structure formation in the junctionless hairpin ribozyme.Biophysical chemistry · 2017Article
- Insight into G-quadruplex-hemin DNAzyme/RNAzyme: adjacent adenine as the intramolecular species for remarkable enhancement of enzymatic activity.Nucleic acids research · 2016Article
- Wobble pairs of the HDV ribozyme play specific roles in stabilization of active site dynamics.Physical chemistry chemical physics : PCCP · 2015Article
- Dynamics of riboswitches: Molecular simulations.Biochimica et biophysica acta · 2014Review
- Principles of ion recognition in RNA: insights from the group II intron structures.RNA (New York, N.Y.) · 2014Article
- Towards Accurate Prediction of Protonation Equilibrium of Nucleic Acids.The journal of physical chemistry letters · 2013Article
- Lewis acid catalysis of phosphoryl transfer from a copper(II)-NTP complex in a kinase ribozyme.Nucleic acids research · 2013Article
- pH-dependent dynamics of complex RNA macromolecules.Journal of chemical theory and computation · 2013Article
- General acid-base catalysis mediated by nucleobases in the hairpin ribozyme.Journal of the American Chemical Society · 2012Article
- Constant pH Molecular Dynamics Simulations of Nucleic Acids in Explicit Solvent.Journal of chemical theory and computation · 2012Article
- QM/MM studies of hairpin ribozyme self-cleavage suggest the feasibility of multiple competing reaction mechanisms.The journal of physical chemistry. B · 2011Article
- The pH dependence of hairpin ribozyme catalysis reflects ionization of an active site adenine.The Journal of biological chemistry · 2011Article
- Metal ions: supporting actors in the playbook of small ribozymes.Metal ions in life sciences · 2011Review
- Deciphering the role of glucosamine-6-phosphate in the riboswitch action of glmS ribozyme.RNA (New York, N.Y.) · 2010Article
- Protonation states of the key active site residues and structural dynamics of the glmS riboswitch as revealed by molecular dynamics.The journal of physical chemistry. B · 2010Article
- Extensive molecular dynamics simulations showing that canonical G8 and protonated A38H+ forms are most consistent with crystal structures of hairpin ribozyme.The journal of physical chemistry. B · 2010Article
- Molecular dynamics and quantum mechanics of RNA: conformational and chemical change we can believe in.Accounts of chemical research · 2010Article
- Theoretical studies of RNA catalysis: hybrid QM/MM methods and their comparison with MD and QM.Methods (San Diego, Calif.) · 2009Review
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3 authors.
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Abstract
Despite numerous structural and biochemical investigations, the catalytic mechanism of hairpin ribozyme self-cleavage remains elusive. To gain insight into the coupling of active site dynamics with activity of this small catalytic RNA, we analyzed a total of approximately 300 ns of molecular dynamics (MD) simulations. Our simulations predict improved global stability for an in vitro selected "gain of function" mutation, which is validated by native gel electrophoretic mobility shift assay. We observe that active site nucleobases and water molecules stabilize a geometry favorable to catalysis through a dynamic hydrogen bonding network. Simulations in which A38 is unprotonated show its N1 move into close proximity of the active site 2'-OH, indicating that A38 may act as a general base during cleavage, a role that has generally been discounted due to the longer distances observed in crystal structures involving inactivating substrate analogs. By contrast, simulations in which N1 of A38 is protonated place N1 in close proximity to the 5'-oxygen leaving group, which supports the proposal that A38 serves as a general acid. In analogy to protein enzymes, we discuss a plausible mechanism in which A38 acts bifunctionally and shuttles a proton directly from the 2'-OH to the 5'-oxygen. Furthermore, our simulations suggest an important role for protonation of N1 of A38 in promoting a favorable geometry similar to that observed in transition-state analog crystal structures, and support previously proposed roles of A38, G8, and long residency water molecules in transition-state stabilization.
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