title: The role of the autoinhibitory domain in differential metal ion activation of calmodulin-stimulated phosphatase.
abstract: Metal ion activators, Ni2+ and Mn2+, have been suggested to induce different conformations of calmodulin (CaM)-stimulated phosphatase. In the present study, an autoinhibitory domain previously implicated in the conformation transition of CaM stimulation of the phosphatase is shown to participate in defining the differential metal ion activation. A proteolytic derivative of the phosphatase deleted from the autoinhibitory domain displayed CaM-independent Mn(2+)-stimulated activity which was about 4-times that of the CaM-stimulated activity of the native enzyme. The Ni(2+)-stimulated activity of the derivative, on the other hand, retained slight CaM-dependence, and the CaM-stimulated activity was 90% of that of the native enzyme. A synthetic peptide corresponding to the autoinhibitory domain could inhibit the Mn(2+)-stimulated activity of the phosphatase derivative by 80%, but had little effect on the Ni(2+)-stimulated activity.
authors.affiliation: Department of Physiology, Nihon University School of Dentistry at Matsudo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yokoyama
authors.forename: J H
authors.initials: JH
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000201:enzymology; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D003546:Cysteine Endopeptidases; D004789:Enzyme Activation; D007700:Kinetics; D008345:Manganese / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009532:Nickel / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D002148:Calmodulin-Binding Proteins; D010446:Peptide Fragments; D008345:Manganese; D009532:Nickel; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D003546:Cysteine Endopeptidases; C019913:clostripain