Key result
Cyclopiazonic acid inhibits the sarcoplasmic reticulum Ca2+-ATPase by reducing its affinity for Ca2+, abolishing transport cooperativity, and limiting binding to a single Ca2+ ion.
Cyclopiazonic acid inhibits the sarcoplasmic reticulum Ca2+-ATPase by altering its Ca2+ binding mechanism, allowing only a single Ca2+ ion to bind and abolishing transport cooperativity.
CPA should not inform clinical SERCA targeting; hypothesis-generating for inhibitor design in cardiac models.
The mycotoxin cyclopiazonic acid (CPA) is a potent inhibitor of the sarcoplasmic reticulum Ca2+-ATPase. The compound decreases the affinity of the Ca2+-ATPase for Ca2+ and reduces the maximum specific activity of the enzyme. Furthermore, CPA abolishes the cooperativity of Ca2+ transport, showing a Ca2+/ATP ratio approximately 1 at any extent of Ca2+ saturation. There is also an effect on the Ca2+-binding mechanism, where the addition of CPA results in binding of only half-maximal amount of Ca2+ observed in its absence. The experimental data suggest that in the presence of CPA, only a single Ca2+ ion binds to the Ca2+-ATPase.
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Francisco Martínez‐Azorín (2004) studied this question. Cyclopiazonic acid (CPA) vs. Absence of CPA was evaluated on Ca2+ binding and transport by Ca2+-ATPase. Cyclopiazonic acid inhibits the sarcoplasmic reticulum Ca2+-ATPase by reducing its affinity for Ca2+, abolishing transport cooperativity, and limiting binding to a single Ca2+ ion.
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