O. V. Bevza1, T. O. Veklich1, O. A. Shkrabak1, R. V. Rodik2, V. I. Kalchenko2, S. O. Kosterin1
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv;
The inhibition of the Na+,K+-АТРase activity of the myometrium cell plasma membranes with calixarene С-107 (5,17-diamino(2-pyridyl)methylphosphono-11,23-di-tret-butyl-26,28-dihydroxy-25,27-dipropoxycalixarene) was investigated. It has been shown that calixarene С-107 reduced the Na+,K+-АТРase activity more efficiently than ouabain did, while it did not practically influence the «basal» Mg2+-АТРase activity of the same membrane. The magnitude of the cofficient of inhibition I0.5 was 33 ± 4 nМ, Hill coefficient was 0.38 ± 0.06. The model calixarene C-150 – the calixarene «scaffold» (26,28-dihydroxy-25,27-dipropoxycalixarene), and the model compound М-3 (4-hydroxyaniline(2-pyridine)methylphosphonic acid) – a fragment of the calixarene С-107, had practically no influence on the enzymatic activity of Na+,K+-АТРase and Mg2+-АТРаse.
We carried out the computer simulation of interaction of calixarenes C-107 and the mentioned model compound with ligand binding sites of the Na+,K+-АТРase of plasma membrane and structure foundation of their intermolecular interaction was found out. The participation of hydrogen, hydrophobic, electrostatic and ?-? (stacking) interaction between calixarene and enzyme aminoacid residues, some of which are located near the active center of Na+,K+-АТРase, was discussed.
Key words: Na+,K+-ATPase, plasma membrane, smooth muscle cells, myometrium, calix-arene C-107, computer simulation, docking.
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