Amino acids Val115-Ile126 of rat gastric H(+)-K(+)-ATPase confer high affinity for Sch-28080 to Na(+)-K(+)-ATPase

The American Journal of Physiology
R M Lyu, R A Farley

Abstract

Na(+)-K(+)-ATPase is inhibited by cardiac glycosides and is insensitive to Sch-28080, an inhibitor of gastric H(+)-K(+)-ATPase. Gastric H(+)-K(+)-ATPase is not inhibited by cardiac glycosides. Both ouabain and, Sch-28080 binding are inhibited by K+, and it has been suggested that the inhibitors bind to corresponding regions on the alpha-subunit of each ion pump. For identification of regions of each pump that interact with the specific inhibitors, chimeric alpha-subunits consisting of selected regions from Na(+)-K(+)-ATPase and gastric H(+)-K(+)-ATPase have been prepared. One chimera (gM1/2) has been constructed from cDNA of the sheep alpha1-subunit of Na(+)-K(+)-ATPase by replacement of the last 12 amino acids of the first predicted transmembrane region (Ile99-Ile110) with corresponding amino acids from rat gastric H(+)-K(+)-ATPase. gM1/2 was expressed in yeast cells together with either the rat Na(+)-K(+)-ATPase beta 1-subunit (NK beta 1) or rat gastric H(+)-K(+)-ATPase beta-subunit (HK beta). Western blots show that the expression level of the chimeric alpha-subunit was comparable to the Na(+)-K(+)-ATPase alpha 1. Ouabain binds with high affinity to gM1/2+NK beta 1 [ouabain binding affinity (Kd) = 9.5 nM] but not to gM1/2+HK...Continue Reading

References

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Citations

Jun 11, 1999·The American Journal of Physiology·F Jaisser, A T Beggah
Oct 31, 2000·The Journal of Biological Chemistry·R A FarleyG Scheiner-Bobis
Mar 5, 2004·The Journal of Pharmacology and Experimental Therapeutics·Keisuke TakeshitaFlorian Gantner
Apr 7, 2000·Leukemia & Lymphoma·S F van Eeden, T Terashima
Mar 6, 1999·The Journal of Biological Chemistry·S AsanoN Takeguchi
Aug 19, 2015·Developmental Biology·Daphne SchatzbergCynthia A Bradham

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