The inhibitors thapsigargin and 2,5‐di(tert‐butyl)‐1,4‐benzohydroquinone favour the E2 form of the Ca2+, Mg2+‐ATPase

Abstract

2,5‐Di(tert‐butyl)‐1,4‐benzohydroquinone has been shown to inhibit the Ca²⁺, Mg²⁺‐ATPase of sarcoplasmic reticulum with an affinity of 0.4 μM. It has been shown to shift the E2‐E1 equilibrium for the ATPase towards E2, as shown previously for the inhibitor thapsigargin. The shift towards E2 results in a decrease in affinity for Ca²⁺, as also observed for thapsigargin. A marked decrease in the rate of the E2‐E1 transition is observed for both BHQ and thapsigargin. A decrease in the equilibrium level of phosphorylation by P_i and of the steady‐state lever of phosphorylation by ATP are consistent with a decrease in the equilibrium constant for phosphorylation by P_i and an increase in the rate of dephosphorylation.