Manganese inhibits Nickel-stimulated Calcineurin Enzyme Activity by Uncompetitive Inhibition

Abstract

Calcineurin (CN), also known as phosphoprotein phosphatase 2B, is a Ca²⁺/calmodulin-dependent protein serine/threonin phosphatase that plays a pivotal role in a variety of cellular functions, such as immune and nerve systems in our body. It has been shown that the phosphatase activity is stimulated by divalent ions, such as nickel (Ni²⁺) and manganese (Mn²⁺) in vitro . In the present study, we examined combined effect of Mn²⁺ and Ni²⁺ on CN activity in vitro . Although the combined effect of Mn²⁺ on Ni²⁺-stimulated CN activity was not observed, we have found that the activity was inhibited by low concentrations of Mn²⁺. To further examine effect of Mn²⁺ inhibition on Ni²⁺-stimulated phosphatase activity, we studied on this inhibition by kinetic analysis. The result showed that Mn²⁺ inhibition of Ni²⁺-stimulated CN activity was uncompetitive inhibition using Lineweaver-Burk plot. Inhibition constant (Ki) for Mn²⁺ was seen at 20.0 μmol/L.