Probing the cation binding site of Na+/K+-ATPase with competitive Na+ antagonists (original) (raw)

The Sodium Pump, 1994

Abstract

Organic guanidium derivatives have been characterized as competitive Na+-like antagonists in Na+/K+-ATPase (2). They compete for Na+ and Rb+ occlusion by Na+/K+-ATPase, and inhibit ATPase activity and Na+-dependent phosphorylation from ATP. Like Na+, they inhibit phosphorylation from inorganic phosphate and stabilize the E1 conformation of FITC-labeled enzyme. Two compounds m- and p- xylylene bisguanidinium, pXBG and mXBG, were found to compete for cation occlusion with the highest affinity (~8μM). This work utilizes pXBG and other Na+-like antagonists to investigate structural and functional properties of the cation binding and transport site of renal Na+/K+-ATPase. The first section summarises experiments which compare the ability of pXBG and other Na+-like antagonists with that of transported alkali metal cations to protect the enzyme against covalent modification and structural perturbations of the cation occlusion site (9). The second section describes experiments with reconstituted proteoliposomes which define the sidedness of inhibition and effects of electrical diffusion potentials on inhibition by Na+ antagonists.

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