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

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  • Additional Information
    • Source:
      Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 0370543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-3773 (Electronic) Linking ISSN: 14337851 NLM ISO Abbreviation: Angew Chem Int Ed Engl Subsets: MEDLINE
    • Publication Information:
      Publication: <2004-> : Weinheim : Wiley-VCH
      Original Publication: Weinheim/Bergstr. : New York, : Verlag Chemie ; Academic Press, c1962-
    • Subject Terms:
      Magnesium/*metabolism ; Phosphates/*metabolism ; RNA, Catalytic/*metabolism; Biocatalysis ; Hydrogen Bonding ; Ions/chemistry ; Ions/metabolism ; Magnesium/chemistry ; Models, Molecular ; Phosphates/chemistry ; RNA, Catalytic/chemistry ; Water/chemistry ; Water/metabolism
    • 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 Mg 2+ 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 Mg 2+ 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 Mg 2+ 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.)
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    • Grant Information:
      M 2517 Austria FWF_ Austrian Science Fund FWF; P 27947 Austria FWF_ Austrian Science Fund FWF; P 31691 Austria FWF_ Austrian Science Fund FWF; P30 CA008748 United States CA NCI NIH HHS
    • Contributed Indexing:
      Keywords: RNA; magnesium; oligonucleotides; reaction mechanisms; structure-function relationships
    • Accession Number:
      0 (Ions)
      0 (Phosphates)
      0 (RNA, Catalytic)
      059QF0KO0R (Water)
      I38ZP9992A (Magnesium)
    • Publication Date:
      Date Created: 20191206 Date Completed: 20210108 Latest Revision: 20210110
    • Publication Date:
      20240829
    • Accession Number:
      PMC7027511
    • Accession Number:
      10.1002/anie.201912522
    • Accession Number:
      31804735