title: Acidity of exogenous metal ion in the activation of calcineurin.
abstract: The pH dependent activation of calcineurin by exogenous metal ion was studied over the pH range from 6.5 to 9.0 in increments of 0.5 pH units. Calcineurin activated by Co2+, Ni2+, or Mg2+ was characterized and compared to the pH dependency of the Mn(2+)-activated enzyme (Martin, B.L., and Graves, D.J. (1986) J. Biol. Chem. 261, 14545-14550). The pH dependency of the kinetic parameters varied with metal ion and subsequent analysis yielded estimates for the pKa values for the enzyme-metal ion and the enzyme-metal ion-substrate complexes with each of the exogenous metal ions characterized. The evaluated pK(a)s for enzyme-metal ion (EM) complexes showed an inverse relationship with the pK(a)s of the M(2+)-H2O complex. In contrast, variation of the pK(a)s for the enzyme-metal ion-substrate (EMS) complexes showed no trend. These data support the hypothesis that exogenous metal ion functions to facilitate a proton transfer before the turnover of substrate with the acidity of the exogenous metal ion as a primary determinant of its participation.
authors.affiliation: Department of Molecular Sciences, University of Tennessee, 858 Madison Avenue, Memphis, TN 38163, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Rhode
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Martin
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism*; D002417:Cattle; D004789:Enzyme Activation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry / Q000494:pharmacology; D008670:Metals / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D007477:Ions; D008670:Metals; D019703:Calcineurin