Samofalova D. Reconstruction spatial structure of the protein phosphates involved in regulation of cytoskeleton in plants, structural and biological mechanisms of their interaction with specific inhibitors

Protein phosphatases associated with the cytoskeleton regulation in plants are considered in the presented Thesis. Characteristics of their interaction with specific inhibitors are studied. As a result of the research, complete plant phosphatomes, represented with serine/threonine-, tyrosine-, and aspartate-specific protein phosphatase superfamilies, were reconstructed. A group of plant protein phosphatases associated with the microtubules regulation has been selected, models of human protein phosphatase and homolog proteins of monocotyledonous and dicotyledonous plants were constructed. Structural and biological features of interaction between inhibitors and plant protein phosphates were established. The original data on ligand-protein interaction sites extends the view of mechanisms that determine the selectivity of known protein phosphatase inhibitors and peculiarities of their structures in higher plant cells. These data are relevant for the subsequent rational design of compounds with antiphosphatase activity. The established differences in the affinity of inhibitors toward different PP1, PP2A and PP4 plants made it possible to optimize the molecular design of new biologically active compounds with increased selectivity against these molecular targets. 5 derivatives of protein phosphatase inhibitors with a higher levels of affinity to the target PP1, PP2A, PP4 were proposed. It is possible to use the described compounds as new effective inhibitors of protein phosphatase in higher plants.