ArticleJournal of the American Chemical Society2015
Role of the active site guanine in the glmS ribozyme self-cleavage mechanism: quantum mechanical/molecular mechanical free energy simulations.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 50 citations in OpenAlex.
- Investigation of the pThe journal of physical chemistry. B · 2021Article
- Beyond the Plateau: pL Dependence of Proton Inventories as a Tool for Studying Ribozyme and Ribonuclease Catalysis.Biochemistry · 2021Article
- Exploring the Minimum-Energy Pathways and Free-Energy Profiles of Enzymatic Reactions with QM/MM Calculations.The journal of physical chemistry. B · 2021Article
- Catalytic Mechanism of Non-Target DNA Cleavage in CRISPR-Cas9 Revealed byACS catalysis · 2020Article
- 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
- Evidence of a General Acid-Base Catalysis Mechanism in the 8-17 DNAzyme.Biochemistry · 2018Article
- Elucidation of Catalytic Strategies of Small Nucleolytic Ribozymes From Comparative Analysis of Active Sites.ACS catalysis · 2018Article
- Metals induce transient folding and activation of the twister ribozyme.Nature chemical biology · 2017Article
- Quantum mechanical force fields for condensed phase molecular simulations.Journal of physics. Condensed matter : an Institute of Physics journal · 2017Article
- A Multidimensional B-Spline Correction for Accurate Modeling Sugar Puckering in QM/MM Simulations.Journal of chemical theory and computation · 2017Article
- Divalent Metal Ion Activation of a Guanine General Base in the Hammerhead Ribozyme: Insights from Molecular Simulations.Biochemistry · 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
- Pressure modulates the self-cleavage step of the hairpin ribozyme.Nature communications · 2017Article
- Assessing the Potential Effects of Active Site MgThe journal of physical chemistry letters · 2016Article
- High-Throughput Mutational Analysis of a Twister Ribozyme.Angewandte Chemie (International ed. in English) · 2016Article
- Molecular Dynamics Study of Twister Ribozyme: Role of Mg(2+) Ions and the Hydrogen-Bonding Network in the Active Site.Biochemistry · 2016Article
- Ambient-Potential Composite Ewald Method for ab Initio Quantum Mechanical/Molecular Mechanical Molecular Dynamics Simulation.Journal of chemical theory and computation · 2016Article
- VR-SCOSMO: A smooth conductor-like screening model with charge-dependent radii for modeling chemical reactions.The Journal of chemical physics · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The glmS ribozyme catalyzes a self-cleavage reaction at the phosphodiester bond between residues A-1 and G1. This reaction is thought to occur by an acid-base mechanism involving the glucosamine-6-phosphate cofactor and G40 residue. Herein quantum mechanical/molecular mechanical free energy simulations and pKa calculations, as well as experimental measurements of the rate constant for self-cleavage, are utilized to elucidate the mechanism, particularly the role of G40. Our calculations suggest that an external base deprotonates either G40(N1) or possibly A-1(O2'), which would be followed by proton transfer from G40(N1) to A-1(O2'). After this initial deprotonation, A-1(O2') starts attacking the phosphate as a hydroxyl group, which is hydrogen-bonded to deprotonated G40, concurrent with G40(N1) moving closer to the hydroxyl group and directing the in-line attack. Proton transfer from A-1(O2') to G40 is concomitant with attack of the scissile phosphate, followed by the remainder of the cleavage reaction. A mechanism in which an external base does not participate, but rather the proton transfers from A-1(O2') to a nonbridging oxygen during nucleophilic attack, was also considered but deemed to be less likely due to its higher effective free energy barrier. The calculated rate constant for the favored mechanism is in agreement with the experimental rate constant measured at biological Mg(2+) ion concentration. According to these calculations, catalysis is optimal when G40 has an elevated pKa rather than a pKa shifted toward neutrality, although a balance among the pKa's of A-1, G40, and the nonbridging oxygen is essential. These results have general implications, as the hammerhead, hairpin, and twister ribozymes have guanines at a similar position as G40.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.