Crucial roles of two hydrated Mg(2+) ions in reaction catalysis of the pistol ribozyme Journal Article
| Authors: | Teplova, M.; Falschlunger, C.; Krasheninina, O.; Egger, M.; Ren, A.; Patel, D. J.; Micura, R. |
| Article Title: | Crucial roles of two hydrated Mg(2+) ions in reaction catalysis of the pistol ribozyme |
| Abstract: | Pistol ribozymes constitute a new class of small self-cleaving RNAs. Crystal structures have been solved, providing three-dimensional snapshots along the reaction coordinate of pistol phosphodiester cleavage, corresponding to the pre-catalytic state, a vanadate mimic of the transition state, and the product. The results led to the proposed underlying chemical mechanism. Importantly, a hydrated Mg2+ ion remains innersphere-coordinated to N7 of G33 in all three states, and is consistent with its likely role as acid in general acid base catalysis (δ and β catalysis). Strikingly, the new structures shed light on a second hydrated Mg2+ ion that approaches the scissile phosphate from its binding site in the pre-cleavage state to reach out for water-mediated hydrogen bonding in the cyclophosphate product. The major role of the second Mg2+ ion appears to be the stabilization of product conformation. This study delivers a mechanistic understanding of ribozyme-catalyzed backbone cleavage. © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. |
| Keywords: | rna; binding sites; catalysis; hydration; oligonucleotides; transition state; magnesium; hydrogen bonds; reaction coordinates; phosphodiesters; reaction mechanisms; ions; chemical mechanism; acid-base catalysis; guns (armament); structure–function relationships; function relationships; reaction catalysis; reaction mechanism |
| Journal Title: | Angewandte Chemie - International Edition |
| Volume: | 59 |
| Issue: | 7 |
| ISSN: | 1433-7851 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2020-02-10 |
| Start Page: | 2837 |
| End Page: | 2843 |
| Language: | English |
| DOI: | 10.1002/anie.201912522 |
| PUBMED: | 31804735 |
| PROVIDER: | scopus |
| PMCID: | PMC7027511 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 March 2020 -- Source: Scopus |
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