TY - GEN
T1 - Na/K-ATPase Glutathionylation: in silico Modeling of Reaction Mechanisms
AU - Solovev, Yaroslav V.
AU - Ostroverkhova, Daria S.
AU - Tamazian, Gaik
AU - Domnin, Anton V.
AU - Anashkina, Anastasya A.
AU - Petrushanko, Irina Yu.
AU - Stepanov, Eugene O.
AU - Porozov, Yu. B.
N1 - 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
PY - 2020/8/18
Y1 - 2020/8/18
N2 - 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.
AB - 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.
KW - Conformer search
KW - Glutathionylation
KW - Hybrid MD
KW - In silico modeling
KW - Na/K-ATPase
KW - PM6-D3H4
UR - http://www.scopus.com/inward/record.url?scp=85090094890&partnerID=8YFLogxK
U2 - 10.1007/978-3-030-57821-3_36
DO - 10.1007/978-3-030-57821-3_36
M3 - Conference contribution
AN - SCOPUS:85090094890
SN - 978-3-030-57820-6
T3 - LNCS
SP - 372
EP - 380
BT - Bioinformatics Research and Applications
PB - Springer Nature
CY - Cham
T2 - 16th International Symposium on Bioinformatics Research and Applications
Y2 - 1 December 2020 through 4 December 2020
ER -