Inhibition of Na<sup>+</sup>/K<sup>+</sup> - and Ca<sup>2+</sup> -ATPase activities by phosphotetradecavanadate
- Author(s)
- Gil Fraqueza, Juan Fuentes, Lukáš Krivosudský, Saikat Dutta, Sib Sankar Mal, Alexander Roller, Gerald Giester, Annette Rompel, Manuel Aureliano
- Abstract
Polyoxometalates (POMs) are promising inorganic inhibitors for P-type ATPases. The experimental models used to study the effects of POMs on these ATPases are usually in vitro models using vesicles from several membrane sources. Very recently, some polyoxotungstates, such as the Dawson anion [P2W18O62](6-), were shown to be potent P-type ATPase inhibitors; being active in vitro as well as in ex-vivo. In the present study we broaden the spectrum of highly active inhibitors of Na+/K+-ATPase from basal membrane of epithelial skin to the bi-capped Keggin-type anion phosphotetradecavanadate Cs(5.6)H(3)APV(14)O(42) (PV14) and we confront the data with activity of other commonly encountered polyoxovanadates, decavanadate (V10) and monovanadate (V-1). The X-ray crystal structure of PV14 was solved and contains two trans-bicapped alpha-Keggin anions HxPV14O42(9-x)-. The anion is built up from the classical Keggin structure [(PO4)@(V12O36)] capped by two [VO] units. PV14 (10 M) exhibited higher ex-vivo inhibitory effect on Na+/K+-ATPase (78%) than was observed at the same concentrations of V-10 (66%) or V-1 (33%). Moreover, PV14 is also a potent in vitro inhibitor of the Ca2+-ATPase activity (IC50 5 mu M) exhibiting stronger inhibition than the previously reported activities for V-10 (15 mu M) and V-1 (80 mu M). Putting it all together, when compared both P-typye ATPases it is suggested that PV14 exibited a high potential to act as an in vivo inhibitor of the Na+/K+-ATPase associated with chloride secretion.
- Organisation(s)
- X-ray Structure Analysis Centre, Department of Inorganic Chemistry, Department of Mineralogy and Crystallography, Department of Biophysical Chemistry
- External organisation(s)
- University of Algarve, Comenius University Bratislava, National Institute of Technology Karnataka, Universität Wien
- Journal
- Journal of Inorganic Biochemistry
- Volume
- 197
- No. of pages
- 7
- ISSN
- 0162-0134
- DOI
- https://doi.org/10.1016/j.jinorgbio.2019.110700
- Publication date
- 04-2019
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 104004 Chemical biology, 105113 Crystallography, 104024 X-ray structural analysis
- Keywords
- ASJC Scopus subject areas
- Biochemistry, Inorganic Chemistry
- Portal url
- https://ucris.univie.ac.at/portal/en/publications/inhibition-of-nak--and-ca2-atpase-activities-by-phosphotetradecavanadate(0d97b7c5-e299-42be-9400-27d790aa9a0b).html