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Crucial Roles of Two Hydrated Mg2+ 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 (? and ? 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.

SUBMITTER: Teplova M 

PROVIDER: S-EPMC7027511 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Crucial Roles of Two Hydrated Mg<sup>2+</sup> Ions in Reaction Catalysis of the Pistol Ribozyme.

Teplova Marianna M   Falschlunger Christoph C   Krasheninina Olga O   Egger Michaela M   Ren Aiming A   Patel Dinshaw J DJ   Micura Ronald R  

Angewandte Chemie (International ed. in English) 20200109 7


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 Mg<sup>2+</sup> ion remains innersphere-coordinated to N7 of G33 in all three states, and is consistent  ...[more]

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