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Publication

Novel insights into the interactions between polyoxometalates and proteins through co-crystallization and X-ray diffraction

Book - Dissertation

Research in the field of proteomics often relies on hydrolysis of proteins into smaller, more manageable fragments. This process requires the usage of a catalyst since the peptide bond has an estimated half-life of 600 years. While proteases are very efficient in hydrolyzing the peptide backbone, they often undergo self-hydrolysis and generate fragments that are too small to match to the protein they were generated from. Most of chemical agents for hydrolysis require harsh reaction conditions, only display partial selectivity and tend to have low yields. A new class of catalysts, metal-substituted polyoxometalates (POMs), has proven to be able to hydrolyze proteins in a regioselective fashion under physiological conditions. Further studies focused on understanding the mechanism behind POM-protein interaction, regioselective cleavage and POM-catalyzed hydrolysis identified a range of POMs that prove to be potential candidates for optimization. Recently, x-ray diffraction of POM-protein co-crystals has given new insights into the interaction between POMs and proteins. Resulting structural models showed binding of catalytically active POMs in the proximity of the reported cleavage sites. However, many questions regarding the mechanism of hydrolysis still remain unanswered. The aim of this project is to expand on the recent x-ray studies, link the acquired data to insights gained from complementary solution studies and improve the design of this class of novel synthetic enzymes. Furthermore, we aimed to use these acquired insights to design and construct self-assembling hybrid frameworks using symmetrical designer proteins. We investigated the role of symmetry, size and shape complementarity on the interactions and the resulting three-dimensional packings that were formed.
Publication year:2020
Accessibility:Open