Na/K-ATPase Glutathionylation: in silico Modeling of Reaction Mechanisms

Yaroslav V. Solovev, Daria S. Ostroverkhova, Gaik Tamazian, Anton V. Domnin, Anastasya A. Anashkina, Irina Yu. Petrushanko, Eugene O. Stepanov, Yu. B. Porozov

Research output

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.
Original languageEnglish
Title of host publicationBioinformatics Research and Applications
Subtitle of host publication16th International Symposium, ISBRA 2020, Moscow, Russia, December 1–4, 2020, Proceedings
Place of PublicationCham
PublisherSpringer Nature
Pages372-380
Number of pages9
ISBN (Electronic)978-3-030-57821-3
ISBN (Print)978-3-030-57820-6
DOIs
Publication statusE-pub ahead of print - 18 Aug 2020
Event16th International Symposium on Bioinformatics Research and Applications - Moscow
Duration: 1 Dec 20204 Dec 2020

Publication series

NameLNCS
Volume12304
ISSN (Print)0302-9743

Conference

Conference16th International Symposium on Bioinformatics Research and Applications
CountryRussian Federation
CityMoscow
Period1/12/204/12/20

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