Zinc inhibits calcineurin activity in vitro by competing with nickel

Calcineurin (CN) is a Ca2+/calmodulin (CaM)-dependent protein serine/threonine phosphatase that contains Zn2+ in its catalytic domain and can be stimulated by divalent ions such as Mn2+ and Ni2+. In this study, the role of exogenous Zn2+ in the regulation of CN activity and its relevance to the role of Ni2+ was investigated. Zn2+ at a concentration range of 10 nM-10 muM inhibited Ni2+-stimulated CN-activity in vitro in a dose-dependent manner and approximately 50% inhibition was attained with 0.25 muM Zn2(+). Kinetic analysis showed that Zn2+ inhibited the activity of CN by competing with Ni2+. Interaction of CN and CaM was not inhibited with Zn2+ at 10 muM. Zn2+ never affected the activity of cAMP phosphodiesterase I or myosin light-chain kinase (CaM-dependent enzymes) and rather activated alkaline phosphatase. The present results indicate that Zn2+ should be a potent inhibitor for CN activity although this ion is essential for CN. (C) 2003 Elsevier Science (USA). All rights reserved.