Cyclopiazonic acid reduces the coupling factor of the Ca2+-ATPase acting on Ca2+ binding.
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.
Departamento de Bioquímica (B-19), Facultad de Medicina (CSIC-UAM), Universidad Autónoma de Madrid, Arturo Duperier 4, E-28029 Madrid, Spain. fazorin@iib.uam.es
Francisco
F
Martínez-Azorín
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D008861:Microsomes; D018482:Muscle, Skeletal / Q000201:enzymology; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases
D004791:Enzyme Inhibitors; D007211:Indoles; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid