CHARACTERIZATION OF ATP BINDING-INHIBITION TO THE SARCOPLASMIC-RETICULUM CA2-ATPASE BY THAPSIGARGIN()

The inhibition of Ca2+-ATPase of sarcoplasmic reticulum by thapsigargi n has been reported to be associated with a suppression of calcium bin ding to the high affinity transport sites. We report here that thapsig argin also acts as an inhibitor of ATP binding by reducing its apparen t affinity by about two orders of magnitude. This inhibition is non-co mpetitive indicating that thapsigargin does not bind to the ATP bindin g site. This is confirmed by the fact that thapsigargin binding to the Ca2+-ATPase does not affect the binding of 2',3'-O-(2,4,6-trinitrocyc lohexadienylidene)-ATP (TNP-ATP).