The importance of the hydroxyl moieties for inhibition of the Ca(2+)-ATPase by trilobolide and 2,5-di(tert-butyl)-1,4-benzohydroquinone.
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.
Wictome
M
M
Department of Biochemistry, University of Southampton, UK.
Holub
M
M
East
J M
JM
Lee
A G
AG
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D005663:Furans / Q000494:pharmacology*; D017665:Hydroxyl Radical; D007700:Kinetics; D009132:Muscles / Q000201:enzymology; D011487:Protein Conformation / Q000187:drug effects; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
D000975:Antioxidants; D016227:Benzoquinones; D002087:Butyrates; D005663:Furans; C067344:2,5-di-tert-butylbenzoquinone; D017665:Hydroxyl Radical; C086352:trilobolide; D000251:Adenosine Triphosphatases; D000252:Calcium-Transporting ATPases