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- W2964658530 endingPage "1456" @default.
- W2964658530 startingPage "1439" @default.
- W2964658530 abstract "The pistol ribozyme (Psr) is among the most recently discovered RNA enzymes and has been the subject of experiments aimed at elucidating the mechanism. Recent biochemical studies have revealed exciting clues about catalytic interactions in the active site not apparent from available crystallographic data. The present work unifies the interpretation of the existing body of structural and functional data on Psr by providing a dynamical model for the catalytically active state in solution from molecular simulation. Our results suggest that a catalytic Mg 2+ ion makes inner-sphere contact with G33:N7 and outer-sphere coordination to the pro- R P of the scissile phosphate, promoting electrostatic stabilization of the dianionic transition state and neutralization of the developing charge of the leaving group through a metal-coordinated water molecule that is made more acidic by a hydrogen bond donated from the 2′OH of P32. This model is consistent with experimental activity-pH and mutagenesis data, including sensitivity to G33(7cG) and phosphorothioate substitution/metal ion rescue. The model suggests several experimentally testable predictions, including the response of cleavage activity to mutations at G42 and P32 positions in the ribozyme, and thio substitutions of the substrate in the presence of different divalent metal ions. Further, the model identifies striking similarities of Psr to the hammerhead ribozyme (HHr), including similar global fold, organization of secondary structure around an active site three-way junction, catalytic metal ion binding mode, and guanine general base. However, the specific binding mode and role of the Mg 2+ ion, as well as a conserved 2′-OH in the active site, are interrelated but subtly different between the ribozymes." @default.
- W2964658530 created "2019-08-13" @default.
- W2964658530 creator A5076436548 @default.
- W2964658530 creator A5078304969 @default.
- W2964658530 date "2019-07-30" @default.
- W2964658530 modified "2023-10-17" @default.
- W2964658530 title "Molecular simulations of the pistol ribozyme: unifying the interpretation of experimental data and establishing functional links with the hammerhead ribozyme" @default.
- W2964658530 cites W1585990551 @default.
- W2964658530 cites W166287601 @default.
- W2964658530 cites W1891814836 @default.
- W2964658530 cites W1969848982 @default.
- W2964658530 cites W1972139720 @default.
- W2964658530 cites W1975820674 @default.
- W2964658530 cites W1979401635 @default.
- W2964658530 cites W1981225934 @default.
- W2964658530 cites W1981253739 @default.
- W2964658530 cites W1983825093 @default.
- W2964658530 cites W1984319638 @default.
- W2964658530 cites W1987565198 @default.
- W2964658530 cites W1992015440 @default.
- W2964658530 cites W1999404678 @default.
- W2964658530 cites W2003698664 @default.
- W2964658530 cites W2024726841 @default.
- W2964658530 cites W2026514619 @default.
- W2964658530 cites W2039917092 @default.
- W2964658530 cites W2047997492 @default.
- W2964658530 cites W2050110866 @default.
- W2964658530 cites W2052044977 @default.
- W2964658530 cites W2058079503 @default.
- W2964658530 cites W2067174909 @default.
- W2964658530 cites W2074240228 @default.
- W2964658530 cites W2081046982 @default.
- W2964658530 cites W2085985889 @default.
- W2964658530 cites W2087220625 @default.
- W2964658530 cites W2101290186 @default.
- W2964658530 cites W2101900479 @default.
- W2964658530 cites W2109783713 @default.
- W2964658530 cites W2114892973 @default.
- W2964658530 cites W2118039681 @default.
- W2964658530 cites W2118528302 @default.
- W2964658530 cites W2130112867 @default.
- W2964658530 cites W2131468364 @default.
- W2964658530 cites W2133751785 @default.
- W2964658530 cites W2134988785 @default.
- W2964658530 cites W2136729627 @default.
- W2964658530 cites W2143875407 @default.
- W2964658530 cites W2144759995 @default.
- W2964658530 cites W2148420129 @default.
- W2964658530 cites W2149199200 @default.
- W2964658530 cites W2153461732 @default.
- W2964658530 cites W2158760873 @default.
- W2964658530 cites W2160498409 @default.
- W2964658530 cites W2162293419 @default.
- W2964658530 cites W2162522101 @default.
- W2964658530 cites W2171563376 @default.
- W2964658530 cites W2178153861 @default.
- W2964658530 cites W2195337028 @default.
- W2964658530 cites W2237727050 @default.
- W2964658530 cites W2238302853 @default.
- W2964658530 cites W2261625992 @default.
- W2964658530 cites W2275900200 @default.
- W2964658530 cites W2289773886 @default.
- W2964658530 cites W2315462435 @default.
- W2964658530 cites W2327005453 @default.
- W2964658530 cites W2328290467 @default.
- W2964658530 cites W2335093845 @default.
- W2964658530 cites W2346647512 @default.
- W2964658530 cites W2402493314 @default.
- W2964658530 cites W2404280981 @default.
- W2964658530 cites W2419909218 @default.
- W2964658530 cites W242058159 @default.
- W2964658530 cites W2468944904 @default.
- W2964658530 cites W2472298146 @default.
- W2964658530 cites W2573677285 @default.
- W2964658530 cites W2574750764 @default.
- W2964658530 cites W2588887966 @default.
- W2964658530 cites W2607077817 @default.
- W2964658530 cites W2609981101 @default.
- W2964658530 cites W2613870238 @default.
- W2964658530 cites W2620098252 @default.
- W2964658530 cites W2765223342 @default.
- W2964658530 cites W2766537639 @default.
- W2964658530 cites W2767146376 @default.
- W2964658530 cites W2770384609 @default.
- W2964658530 cites W2771262230 @default.
- W2964658530 cites W2777570659 @default.
- W2964658530 cites W2891791233 @default.
- W2964658530 cites W2941843676 @default.
- W2964658530 cites W2945380370 @default.
- W2964658530 cites W2946396630 @default.
- W2964658530 cites W4237468509 @default.
- W2964658530 cites W4253399616 @default.
- W2964658530 cites W97434050 @default.
- W2964658530 doi "https://doi.org/10.1261/rna.071944.119" @default.
- W2964658530 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6795133" @default.
- W2964658530 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31363004" @default.
- W2964658530 hasPublicationYear "2019" @default.
- W2964658530 type Work @default.