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

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

SUBMITTER: Wieruszewska J 

PROVIDER: S-EPMC11101458 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature