ArticleJournal of the American Chemical Society2011
The glmS ribozyme tunes the catalytically critical pK(a) of its coenzyme glucosamine-6-phosphate.
Article in Journal of the American Chemical Society, 2011. 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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24 citing papers in PubMed, 36 citations in OpenAlex.
- Self-cleaving ribozymes: substrate specificity and synthetic biology applications.RSC chemical biology · 2021Review
- Nucleic Acid Catalysis under Potential Prebiotic Conditions.Chemistry, an Asian journal · 2020Review
- Elucidation of Catalytic Strategies of Small Nucleolytic Ribozymes From Comparative Analysis of Active Sites.ACS catalysis · 2018Article
- A divalent cation-dependent variant of theRNA (New York, N.Y.) · 2017Article
- Assessing the Potential Effects of Active Site MgThe journal of physical chemistry letters · 2016Article
- In vitro evolution of coenzyme-independent variants from the glmS ribozyme structural scaffold.Methods (San Diego, Calif.) · 2016Article
- Chemistry and Biology of Self-Cleaving Ribozymes.Trends in biochemical sciences · 2015Review
- Two Divalent Metal Ions and Conformational Changes Play Roles in the Hammerhead Ribozyme Cleavage Reaction.Biochemistry · 2015Article
- Chemical feasibility of the general acid/base mechanism of glmS ribozyme self-cleavage.Biopolymers · 2015Article
- Inverse thio effects in the hepatitis delta virus ribozyme reveal that the reaction pathway is controlled by metal ion charge density.Biochemistry · 2015Article
- Role of the active site guanine in the glmS ribozyme self-cleavage mechanism: quantum mechanical/molecular mechanical free energy simulations.Journal of the American Chemical Society · 2015Article
- Role of tautomerism in RNA biochemistry.RNA (New York, N.Y.) · 2015Review
- Phosphatase-inert glucosamine 6-phosphate mimics serve as actuators of the glmS riboswitch.ACS chemical biology · 2014Article
- Nucleic acid catalysis: metals, nucleobases, and other cofactors.Chemical reviews · 2014Review
- Quantum mechanical/molecular mechanical free energy simulations of the self-cleavage reaction in the hepatitis delta virus ribozyme.Journal of the American Chemical Society · 2014Article
- Direct observation of multiple tautomers of oxythiamine and their recognition by the thiamine pyrophosphate riboswitch.ACS chemical biology · 2014Article
- Experimental approaches for measuring pKa's in RNA and DNA.Methods in enzymology · 2014Article
- An in vitro evolved glmS ribozyme has the wild-type fold but loses coenzyme dependence.Nature chemical biology · 2013Article
- Glucosamine and glucosamine-6-phosphate derivatives: catalytic cofactor analogues for the glmS ribozyme.The Journal of organic chemistry · 2013Article
- Lewis acid catalysis of phosphoryl transfer from a copper(II)-NTP complex in a kinase ribozyme.Nucleic acids research · 2013Article
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4 authors at 3 institutions in 1 country.
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Abstract
The glmS ribozyme riboswitch is the first known natural catalytic RNA that employs a small-molecule cofactor. Binding of glucosamine-6-phosphate (GlcN6P) uncovers the latent self-cleavage activity of the RNA, which adopts a catalytically competent conformation that is nonetheless inactive in the absence of GlcN6P. Structural and analogue studies suggest that the amine of GlcN6P functions as a general acid-base catalyst, while its phosphate is important for binding affinity. However, the solution pK(a) of the amine is 8.06 ± 0.05, which is not optimal for proton transfer. Here we used Raman crystallography directly to determine the pK(a)'s of GlcN6P bound to the glmS ribozyme. Binding to the RNA lowers the pK(a) of the amine of GlcN6P to 7.26 ± 0.09 and raises the pK(a) of its phosphate to 6.35 ± 0.09. Remarkably, the pK(a)'s of these two functional groups are unchanged from their values for free GlcN6P (8.06 ± 0.05 and 5.98 ± 0.05, respectively) when GlcN6P binds to the catalytically inactive but structurally unperturbed G40A mutant of the ribozyme, thus implicating the ribozyme active site guanine in pK(a) tuning. This is the first demonstration that a ribozyme can tune the pK(a) of a small-molecule ligand. Moreover, the anionic glmS ribozyme in effect stabilizes the neutral amine of GlcN6P by lowering its pK(a). This is unprecedented and illustrates the chemical sophistication of ribozyme active sites.
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