Biochemical and Biophysical Research Communications 1994-03-15

The importance of the hydroxyl moieties for inhibition of the Ca(2+)-ATPase by trilobolide and 2,5-di(tert-butyl)-1,4-benzohydroquinone.

M Wictome, M Holub, J M East, A G Lee

Index: Biochem. Biophys. Res. Commun. 199(2) , 916-21, (1994)

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Abstract

Trilobolide and 2,5-di(tert-butyl)-1,4-benzohydroquinone (BHQ) are potent inhibitors of the Ca(2+)-ATPase of skeletal muscle sarcoplasmic reticulum. Desoxytrilobolide and 2,5-di(tert-butyl)-1,4-diacetylphenol (acetyl-BHQ) have much lower potencies than their parent compounds and 2,5-di(tert-butyl)-1,4-benzoquinone (BQ) has no effect on ATPase activity. Studies using the ATPase labelled with 4-nitrobenzo-2-oxa-1,3-diazole (NBD) suggest that both trilobolide and BHQ bind more strongly to the E2 conformation of the ATPase than to the E1 conformation. Desoxytrilobolide, acetyl-BHQ and BQ have little effect on the E1/E2 equilibrium. Studies with mixtures of trilobolide and desoxytrilobolide suggest that the inactive derivatives are unable to bind to the ATPase.