The 8-17 DNAzyme can operate in a single active structure regardless of metal ion cofactor.

Autor: Wieruszewska J; Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704, Poznań, Noskowskiego, 12/14, Poland., Pawłowicz A; Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704, Poznań, Noskowskiego, 12/14, Poland., Połomska E; Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704, Poznań, Noskowskiego, 12/14, Poland., Pasternak K; Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704, Poznań, Noskowskiego, 12/14, Poland., Gdaniec Z; Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704, Poznań, Noskowskiego, 12/14, Poland., Andrałojć W; Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61-704, Poznań, Noskowskiego, 12/14, Poland. wandralojc@ibch.poznan.pl.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 May 17; Vol. 15 (1), pp. 4218. Date of Electronic Publication: 2024 May 17.
DOI: 10.1038/s41467-024-48638-x
Abstrakt: DNAzymes - synthetic enzymes made of DNA - have long attracted attention as RNA-targeting therapeutic agents. Yet, as of now, no DNAzyme-based drug has been approved, partially due to our lacking understanding of their molecular mode of action. In this work we report the solution structure of 8-17 DNAzyme bound to a Zn 2+ ion solved through NMR spectroscopy. Surprisingly, it turned out to be very similar to the previously solved Pb 2+ -bound form (catalytic domain RMSD = 1.28 Å), despite a long-standing literature consensus that Pb 2+ recruits a different DNAzyme fold than other metal ion cofactors. Our follow-up NMR investigations in the presence of other ions - Mg 2+ , Na + , and Pb 2+ - suggest that at DNAzyme concentrations used in NMR all these ions induce a similar tertiary fold. Based on these findings, we propose a model for 8-17 DNAzyme interactions with metal ions postulating the existence of only a single catalytically-active structure, yet populated to a different extent depending on the metal ion cofactor. Our results provide structural information on the 8-17 DNAzyme in presence of non-Pb 2+ cofactors, including the biologically relevant Mg 2+ ion.
(© 2024. The Author(s).)
Databáze: MEDLINE
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