Role of homologous ASP334 and GLU319 in human non-gastric H,K- and Na,K-ATPases in cardiac glycoside binding

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Serval ID
serval:BIB_C653864473A8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Role of homologous ASP334 and GLU319 in human non-gastric H,K- and Na,K-ATPases in cardiac glycoside binding
Journal
Biochemical and Biophysical Research Communications
Author(s)
Radkov R., Kharoubi-Hess S., Schaer D., Modyanov N. N., Geering K., Horisberger J. D.
ISSN
0006-291X (Print)
Publication state
Published
Issued date
04/2007
Peer-reviewed
Oui
Volume
356
Number
1
Pages
142-6
Language
english
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Apr 27
Abstract
Cardiac steroids inhibit Na,K-ATPase and the related non-gastric H,K-ATPase, while they do not interact with gastric H,K-ATPase. Introducing an arginine, the residue present in the gastric H,K-ATPase, in the second extracellular loop at the corresponding position 334 in the human non-gastric H,K-ATPase (D334R mutation) rendered it completely resistant to 2mM ouabain. The corresponding mutation (E319R) in alpha1 Na,K-ATPase produced a approximately 2-fold increase of the ouabain IC(50) in the ouabain-resistant rat alpha1 Na,K-ATPase and a large decrease of the ouabain affinity of human alpha1 Na,K-ATPase, on the other hand this mutation had no effect on the affinity for the aglycone ouabagenin. These results provide a strong support for the orientation of ouabain in its biding site with its sugar moiety interacting directly with the second extracellular loop.
Keywords
Amino Acid Sequence *Amino Acid Substitution Animals Aspartic Acid/genetics Binding, Competitive/drug effects Biological Transport/drug effects Cardiac Glycosides/*metabolism Dose-Response Relationship, Drug Enzyme Inhibitors/pharmacology Female Glutamic Acid/genetics H(+)-K(+)-Exchanging ATPase/antagonists & inhibitors/genetics/*metabolism Humans Membrane Potentials/drug effects Mutation Na(+)-K(+)-Exchanging ATPase/antagonists & inhibitors/genetics/*metabolism Oocytes/drug effects/metabolism/physiology Ouabain/analogs & derivatives/pharmacology Protein Subunits/antagonists & inhibitors/genetics/metabolism Rabbits Rats Rubidium Radioisotopes/pharmacokinetics Sequence Homology, Amino Acid Xenopus laevis
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Web of science
Create date
24/01/2008 12:28
Last modification date
20/08/2019 15:41
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