8OR8

Solution structure of the 8-17 DNAzyme in presence of Zn2+

Summary for 8OR8

• Entry DOI: 10.2210/pdb8or8/pdb
• NMR Information: BMRB: 34805
• Descriptor: 8-17 DNAzyme (1 entity in total)
• Functional Keywords: dnazyme, 8-17, zinc, dna
• Biological source: synthetic construct
• Total number of polymer chains: 1
• Total formula weight: 10841.92

Authors

Andralojc, W.,Gdaniec, Z. (deposition date: 2023-04-13, release date: 2023-04-26, Last modification date: 2024-06-19)

Primary citation

Wieruszewska, J.,Pawlowicz, A.,Polomska, E.,Pasternak, K.,Gdaniec, Z.,Andralojc, W.
The 8-17 DNAzyme can operate in a single active structure regardless of metal ion cofactor.
Nat Commun, 15:4218-4218, 2024

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

PubMed: 38760331
DOI: 10.1038/s41467-024-48638-x

Experimental method

SOLUTION NMR