Acidity of exogenous metal ion in the activation of calcineurin

Authors: Rhode D.J.¹; Martin B.L.²

Source: BioMetals, Volume 17, Number 4, August 2004 , pp. 399-407(9)

Publisher: Springer

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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 Mn²⁺-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 pK_a values for the enzyme-metal ion and the enzyme-metal ion-substrate complexes with each of the exogenous metal ions characterized. The evaluated pK_as for enzyme-metal ion (EM) complexes showed an inverse relationship with the pK_as of the M²⁺-H₂O complex. In contrast, variation of the pK_as 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.

Keywords: calcineurin; metal-activated enzyme; activation; pH dependency; metal ion; acidity

Document Type: Research article

DOI: http://dx.doi.org/10.1023/B:BIOM.0000029435.98167.d6

Affiliations: 1: Department of Molecular Sciences, University of Tennessee, 858 Madison Avenue, Memphis, TN 38163 2: Department of Molecular Sciences, University of Tennessee, 858 Madison Avenue, Memphis, TN 38163 current address: Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street, SE, Minneapolis, MN 55455 Phone: 612-625-5988 marti285@umn.edu, Email: marti285@umn.edu

Publication date: 2004-08-01