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

Author

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  • Julia Wieruszewska

    (Polish Academy of Sciences, 61-704)

  • Aleksandra Pawłowicz

    (Polish Academy of Sciences, 61-704)

  • Ewa Połomska

    (Polish Academy of Sciences, 61-704)

  • Karol Pasternak

    (Polish Academy of Sciences, 61-704)

  • Zofia Gdaniec

    (Polish Academy of Sciences, 61-704)

  • Witold Andrałojć

    (Polish Academy of Sciences, 61-704)

Abstract

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 Zn2+ ion solved through NMR spectroscopy. Surprisingly, it turned out to be very similar to the previously solved Pb2+-bound form (catalytic domain RMSD = 1.28 Å), despite a long-standing literature consensus that Pb2+ recruits a different DNAzyme fold than other metal ion cofactors. Our follow-up NMR investigations in the presence of other ions — Mg2+, Na+, and Pb2+ – 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-Pb2+ cofactors, including the biologically relevant Mg2+ ion.

Suggested Citation

  • Julia Wieruszewska & Aleksandra Pawłowicz & Ewa Połomska & Karol Pasternak & Zofia Gdaniec & Witold Andrałojć, 2024. "The 8-17 DNAzyme can operate in a single active structure regardless of metal ion cofactor," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48638-x
    DOI: 10.1038/s41467-024-48638-x
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    References listed on IDEAS

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    1. Almudena Ponce-Salvatierra & Katarzyna Wawrzyniak-Turek & Ulrich Steuerwald & Claudia Höbartner & Vladimir Pena, 2016. "Crystal structure of a DNA catalyst," Nature, Nature, vol. 529(7585), pages 231-234, January.
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    Cited by:

    1. Jessica Felice Schmuck & Jan Borggräfe & Manuel Etzkorn, 2024. "The dynamic world of the 8–17 DNAzyme," Nature Communications, Nature, vol. 15(1), pages 1-3, December.

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    1. Jessica Felice Schmuck & Jan Borggräfe & Manuel Etzkorn, 2024. "The dynamic world of the 8–17 DNAzyme," Nature Communications, Nature, vol. 15(1), pages 1-3, December.

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