ArticleThe journal of physical chemistry. B2010
Protonation states of the key active site residues and structural dynamics of the glmS riboswitch as revealed by molecular dynamics.
Article in The journal of physical chemistry. B, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 58 citations in OpenAlex.
- Optimized periphery-core interface increases fitness of the Bacillus subtilis glmS ribozyme.Nucleic acids research · 2024Article
- Structural Studies of the 3',3'-cGAMP Riboswitch Induced by Cognate and Noncognate Ligands Using Molecular Dynamics Simulation.International journal of molecular sciences · 2018Article
- An intricate balance of hydrogen bonding, ion atmosphere and dynamics facilitates a seamless uracil to cytosine substitution in the U-turn of the neomycin-sensing riboswitch.Nucleic acids research · 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
- Assessing the Potential Effects of Active Site MgThe journal of physical chemistry letters · 2016Article
- Influence of surface charge, binding site residues and glycosylation on Thielavia terrestris cutinase biochemical characteristics.Applied microbiology and biotechnology · 2016Article
- Molecular mechanism for preQ1-II riboswitch function revealed by molecular dynamics.RNA (New York, N.Y.) · 2015Article
- Chemical feasibility of the general acid/base mechanism of glmS ribozyme self-cleavage.Biopolymers · 2015Article
- The energy landscape of adenylate kinase during catalysis.Nature structural & molecular biology · 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
- Phosphatase-inert glucosamine 6-phosphate mimics serve as actuators of the glmS riboswitch.ACS chemical biology · 2014Article
- Dynamics of riboswitches: Molecular simulations.Biochimica et biophysica acta · 2014Review
- Reduced model captures Mg(2+)-RNA interaction free energy of riboswitches.Biophysical journal · 2014Article
- Towards Accurate Prediction of Protonation Equilibrium of Nucleic Acids.The journal of physical chemistry letters · 2013Article
- pH-dependent dynamics of complex RNA macromolecules.Journal of chemical theory and computation · 2013Article
- Molecular mechanism of preQ1 riboswitch action: a molecular dynamics study.The journal of physical chemistry. B · 2012Article
- Molecular dynamics simulations of G-DNA and perspectives on the simulation of nucleic acid structures.Methods (San Diego, Calif.) · 2012Review
- Mechanism and distribution of glmS ribozymes.Methods in molecular biology (Clifton, N.J.) · 2012Article
- Charged nucleobases and their potential for RNA catalysis.Accounts of chemical research · 2011Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The glmS catalytic riboswitch is part of the 5'-untranslated region of mRNAs encoding glucosamine-6-phosphate (GlcN6P) synthetase (glmS) in numerous gram-positive bacteria. Binding of the cofactor GlcN6P induces site-specific self-cleavage of the RNA. However, the detailed reaction mechanism as well as the protonation state of the glmS reactive form still remains elusive. To probe the dominant protonation states of key active site residues, we carried out explicit solvent molecular dynamic simulations involving various protonation states of three crucial active site moieties observed in the available crystal structures: (i) guanine G40 (following the Thermoanaerobacter tengcongensis numbering), (ii) the GlcN6P amino/ammonium group, and (iii) the GlcN6P phosphate moiety. We found that a deprotonated G40(-) seems incompatible with the observed glmS active site architecture. Our data suggest that the canonical form of G40 plays a structural role by stabilizing an in-line attack conformation of the cleavage site A-1(2'-OH) nucleophile, rather than a more direct chemical role. In addition, we observe weakened cofactor binding upon protonation of the GlcN6P phosphate moiety, which explains the experimentally observed increase in K(m) with decreasing pH. Finally, we discuss a possible role of cofactor binding and its interaction with the G65 and G1 purines in structural stabilization of the A-1(2'-OH) in-line attack conformation. On the basis of the identified dominant protonation state of the reaction precursor, we propose a hypothesis of the self-cleavage mechanism in which A-1(2'-OH) is activated as a nucleophile by the G1(pro-R(p)) nonbridging oxygen of the scissile phosphate, whereas the ammonium group of GlcN6P acts as the general acid protonating the G1(O5') leaving group.
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