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Acidity of exogenous metal ion in the activation of calcineurin

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

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Article Open access 28 August 2020

Trevor P. Creamer

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  1. Bruce L. Martin

    Present address: Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Delaware Street, SE, Minneapolis, MN, 55455

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  1. Department of Molecular Sciences, University of Tennessee, 858 Madison Avenue, Memphis, TN 38163

    David J. Rhode & Bruce L. Martin

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Rhode, D.J., Martin, B.L. Acidity of exogenous metal ion in the activation of calcineurin. Biometals 17, 399–407 (2004). https://doi.org/10.1023/B:BIOM.0000029435.98167.d6

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  • DOI: https://doi.org/10.1023/B:BIOM.0000029435.98167.d6

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