title: Binding site of omeprazole in hog gastric H+,K(+)-ATPase.
abstract: Omeprazole transforms into an active compound in an acidic environment, which is able to modify a sulfhydryl group of gastric H+,K(+)-ATPase. Omeprazole was transformed into a strongly fluorescent molecule by UV-light irradiation (excitation wavelength = 290 nm, emission wavelength = 335 nm). The omeprazole-modified residue of hog H+,K(+)-ATPase was estimated by the fluorescence of the omeprazole moiety and limited tryptic digestion of the enzyme. Among the four main tryptic digested subfragments, omeprazole was bound to the 67, 42 and 32-kDa subfragments, but not to the 52-kDa subfragment. Taking the amino acid sequence of this ATPase into consideration, we propose that omeprazole specifically binds with Cys322 in hog H+,K(+)-ATPase (Cys321 in rat).
authors.affiliation: Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Morii
authors.forename: H
authors.initials: H
authors.lastname: Takata
authors.forename: N
authors.initials: N
authors.lastname: Takeguchi
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000201:enzymology; D003545:Cysteine; D017506:H(+)-K(+)-Exchanging ATPase; D008970:Molecular Weight; D009130:Muscle, Smooth / Q000201:enzymology; D009853:Omeprazole / Q000378:metabolism*; D010446:Peptide Fragments / Q000302:isolation & purification; D010449:Peptide Mapping; D013050:Spectrometry, Fluorescence; D013270:Stomach / Q000201:enzymology*; D013552:Swine; D014357:Trypsin
chemical_list: D010446:Peptide Fragments; D014357:Trypsin; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D003545:Cysteine; D009853:Omeprazole