Cyclopiazonic acid reduces the coupling factor of the Ca 2+-ATPase acting on Ca 2+ binding

Abstract

The mycotoxin cyclopiazonic acid (CPA) is a potent inhibitor of the sarcoplasmic reticulum Ca 2+-ATPase. The compound decreases the affinity of the Ca 2+-ATPase for Ca 2+ and reduces the maximum specific activity of the enzyme. Furthermore, CPA abolishes the cooperativity of Ca 2+ transport, showing a Ca 2+/ATP ratio ∼1 at any extent of Ca 2+ saturation. There is also an effect on the Ca 2+-binding mechanism, where the addition of CPA results in binding of only half-maximal amount of Ca 2+ observed in its absence. The experimental data suggest that in the presence of CPA, only a single Ca 2+ ion binds to the Ca 2+-ATPase.