RESUMEN
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.
Asunto(s)
ADN Catalítico , Plomo , Magnesio , Zinc , ADN Catalítico/química , ADN Catalítico/metabolismo , Magnesio/metabolismo , Magnesio/química , Zinc/metabolismo , Zinc/química , Plomo/química , Plomo/metabolismo , Conformación de Ácido Nucleico , Dominio Catalítico , Modelos Moleculares , Sodio/metabolismo , Sodio/química , Metales/metabolismo , Metales/química , Espectroscopía de Resonancia Magnética , IonesRESUMEN
We report the synthesis and characterization of a coordination architecture with a Fe(ii) center obtained by subcomponent self-assembly in water. The complex is based on very rare hemi-iminal ligands spontaneously generated from commercially available materials. The complex can be further transformed into another species by oxidation reaction of both the metal center and organic ligand.