title: Evidence for a common binding site for omeprazole and N-ethylmaleimide in subunit A of chromaffin granule vacuolar-type H(+)-ATPase.
abstract: Vacuolar-type H(+)-ATPase from adrenal chromaffin granules was found to be sensitive to omeprazole, a known gastric H+/K(+)-ATPase inhibitor, the concentration required for 50% inhibition being 80 microM freshly-prepared and 12 microM acid-treated reagent. ATP and ADP protected the enzyme from inhibition by omeprazole. The activity of the inhibited enzyme was restored by the addition of reduced glutathione. Omeprazole protected the enzyme from inhibition by N-ethylmaleimide and its binding to the subunit A. As subunit A has a nucleotide binding site(s) and as a cysteine residue is involved in the inhibition by N-ethylmaleimide, these results suggested that the two sulfhydryl reagents bind to the same cysteine residue near the nucleotide binding domain in the subunit A, resulting in inactivation of vacuolar-type H(+)-ATPase.
authors.affiliation: Department of Biochemistry and Organic Chemistry, Osaka University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Moriyama
authors.forename: V
authors.initials: V
authors.lastname: Patel
authors.forename: I
authors.initials: I
authors.lastname: Ueda
authors.forename: M
authors.initials: M
authors.lastname: Futai
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000313:Adrenal Medulla / Q000201:enzymology*; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002837:Chromaffin Granules / Q000201:enzymology*; D005033:Ethylmaleimide / Q000378:metabolism*; D007700:Kinetics; D046911:Macromolecular Substances; D009853:Omeprazole / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D014617:Vacuoles / Q000201:enzymology
chemical_list: D046911:Macromolecular Substances; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D009853:Omeprazole; D005033:Ethylmaleimide