Inhibitory effect of okadaic acid on protein phosphatases: characteristics as a tightly binding inhibitor

Abstract

Okadaic acid is the first exogenous substance that has been described to have a potent and specific inhibitory effect on type 2A-, type 1- and type 2B- protein phosphatases, whose catalytic subunits have a striking sequence homology. Of these types of enzyme, type 2A-phosphatase is most strongly inhibited by okadaic acid. The dissociation constant for the interaction between this enzyme and okadaic acid is estimated to be 30pM. As expected from the kinetic theory for tightly binding inhibitors, the dose-inhibition relationship is markedly shifted to the right and became steeper when the concentration of the enzyme is increased. The concentrations of okadaic acfd for 50% inhibition of type 1 and type 2B-phosphatases are 200 nM and 5 μM, respectively. Kinetic studies have shown that okadaic acid acts as a non-competitive or mixed inhibitor on the okadaic acid-sensitive enzymes.