ABSTRACT
Structural biology is focused on understanding the architecture of biomolecules, such as proteins and nucleic acids. Deciphering the structure helps to understand their function in the cell at a very precise molecular level. This makes it possible to not only determine the basis of diseases but also to propose therapeutic strategies and tools. Such a strong motivation for the development of structural biology has led to the development of a number of methods, which enable determination of the structures of the molecules of life. The continuous progress has been enabled by the integration of biology, chemistry, physics, and computer science, making structural biology extremely interdisciplinary. In its 35-year history, the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznan has become one of the key Polish institutions conducting research in the field of structural biology. On one hand, the research has brought international recognition, and on the other hand, it has forced the implementation and development of cutting-edge methods. This review discusses the methods used in structural biology at the Institute.
Subject(s)
Proteins , Poland , Proteins/chemistry , Molecular Biology , Nucleic Acids/chemistry , HumansABSTRACT
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.
Subject(s)
DNA, Catalytic , Lead , Magnesium , Zinc , DNA, Catalytic/chemistry , DNA, Catalytic/metabolism , Magnesium/metabolism , Magnesium/chemistry , Zinc/metabolism , Zinc/chemistry , Lead/chemistry , Lead/metabolism , Nucleic Acid Conformation , Catalytic Domain , Models, Molecular , Sodium/metabolism , Sodium/chemistry , Metals/metabolism , Metals/chemistry , Magnetic Resonance Spectroscopy , IonsABSTRACT
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.