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 [P

2

W

18

O

62

]

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

3.4

PV

14

O

42

(PV

14

)and we confront the data with activity of other commonly encountered polyoxovanadates, decavanadate (V

10

)and monovanadate (V

1

). The X-ray crystal structure of PV

14

was solved and contains two trans-bicapped α-Keggin anions H

x

PV

14

O

42

 

(9-x)-

. The anion is built up from the classical Keggin structure [(PO

4

)@(V

12

O

36

)]capped by two [VO]units. PV

14

(10 μM)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, PV

14

is also a potent in vitro inhibitor of the Ca

2+

-ATPase activity (IC

50

5 μM)exhibiting stronger inhibition than the previously reported activities for V

10

(15 μM)and V

1

(80 μM). Putting it all together, when compared both P-typye ATPases it is suggested that PV

14

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
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
Publication status
E-pub ahead of print
Peer reviewed
Yes
Austrian Fields of Science 2012
104004 Chemical biology, 104003 Inorganic chemistry, 104024 X-ray structural analysis, 105113 Crystallography
Keywords
Decavanadate, Epithelial chloride secretion, P-type ATPases, Phosphotetradecavanadate, Polyoxometalates
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