Role of homologous ASP334 and GLU319 in human non-gastric H,K- and Na,K-ATPases in cardiac glycoside binding
Détails
Télécharger: 17349614_Postprint.pdf (566.20 [Ko])
Etat: Public
Version: de l'auteur⸱e
Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_C653864473A8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Role of homologous ASP334 and GLU319 in human non-gastric H,K- and Na,K-ATPases in cardiac glycoside binding
Périodique
Biochemical and Biophysical Research Communications
ISSN
0006-291X (Print)
Statut éditorial
Publié
Date de publication
04/2007
Peer-reviewed
Oui
Volume
356
Numéro
1
Pages
142-6
Langue
anglais
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Apr 27
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Apr 27
Résumé
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.
Mots-clé
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
Pubmed
Web of science
Création de la notice
24/01/2008 13:28
Dernière modification de la notice
20/08/2019 16:41