Abstract
Na,K-ATPase is a redox-sensitive transmembrane protein. Understanding the mechanisms of Na,K-ATPase redox regulation can help to prevent impairment of Na,K-ATPase functioning under pathological conditions and reduce damage and death of cells. One of the basic mechanisms to protect Na,K-ATPase against stress oxidation is the glutathionylation reaction that is aimed to reduce several principal oxidized cysteines (244, 458, and 459) that are involved in Na,K-ATPase action regulation. In this study, we carried out in silico modeling to evaluate glutathione affinity on various stages of Na,K-ATPase action cycle, as well as to discover a reaction mechanism of disulfide bond formation between reduced glutathione and oxidized cysteine. To achieve this goal both glutathione and Na,K-ATPase conformer sampling was applied, the reliability of the protein-ligand complexes was examined by MD assay, the reaction mechanism was studied using semi-empirical PM6-D3H4 approach that could have a deal with large organic systems optimization.
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Acknowledgments
This work (except conformational movement modeling) has been supported by the Russian Science Foundation (grant No. 19-14-00374). The conformational movement modeling has been performed under support of the Russian Science Foundation (grant No 19-71-30020).
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Solovev, Y.V. et al. (2020). Na/K-ATPase Glutathionylation: in silico Modeling of Reaction Mechanisms. In: Cai, Z., Mandoiu, I., Narasimhan, G., Skums, P., Guo, X. (eds) Bioinformatics Research and Applications. ISBRA 2020. Lecture Notes in Computer Science(), vol 12304. Springer, Cham. https://doi.org/10.1007/978-3-030-57821-3_36
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DOI: https://doi.org/10.1007/978-3-030-57821-3_36
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