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

Autor:	Rossen Radkov, Solange Kharoubi-Hess, Danièle Schaer, Käthi Geering, Jean-Daniel Horisberger, Nikolai N. Modyanov
Rok vydání:	2007
Předmět:	Arginine ATPase Biophysics Glutamic Acid Biology H(+)-K(+)-Exchanging ATPase Binding Competitive Biochemistry Article Ouabain Membrane Potentials Cardiac Glycosides 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 Xenopus laevis chemistry.chemical_compound Extracellular medicine Animals Humans Amino Acid Sequence Enzyme Inhibitors Na+/K+-ATPase Molecular Biology Cardiac glycoside Aspartic Acid Dose-Response Relationship Drug Sequence Homology Amino Acid Biological Transport Proton Pump Inhibitors Cell Biology Molecular biology Rats Protein Subunits Aglycone Amino Acid Substitution chemistry Mutation Oocytes biology.protein Female Rabbits Sodium-Potassium-Exchanging ATPase Rubidium Radioisotopes medicine.drug
Zdroj:	Biochemical and Biophysical Research Communications, vol. 356, no. 1, pp. 142-6
ISSN:	0006-291X
DOI:	10.1016/j.bbrc.2007.02.119
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d1a2ea1f58dda6a4087dd8fa3573114 https://doi.org/10.1016/j.bbrc.2007.02.119 Zobrazit plný text záznamu Full Text from ScienceDirect