Quinacrine mustard and lipophilic cations inhibitory to both vacuolar H(+)-ATPase and F0F1-ATP synthase.
Various lipophilic cations, such as quinacrine mustard and dequalinium, which are known to inhibit mitochondrial F1-ATPase, strongly inhibited vacuolar H(+)-ATPase purified from bovine adrenal chromaffin granules. Quinacrine mustard bound irreversibly to vacuolar H(+)-ATPase subunit A, and the 115 kDa accessory polypeptide and dithiothreitol had no effect. The binding was competitively inhibited by chlorpromazine and quinacrine, and these compounds specifically reduced the amount of labeling of subunit A. Quinacrine mustard also prevented the binding of [alpha-32P]ATP to subunit A but had no effect on the binding of [3H]N-ethylmaleimide to either subunit A or the 115 kDa accessory polypeptide. These results suggest that the binding site of quinacrine mustard in subunit A is not related to the N-ethylmaleimide-binding site(s), which is important for activity.
Moriyama
Y
Y
Department of Biochemistry and Organic Chemistry, Osaka University, Japan.
Patel
V
V
Futai
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000201:enzymology; D002412:Cations; D002417:Cattle; D002746:Chlorpromazine / Q000494:pharmacology; D002837:Chromaffin Granules / Q000201:enzymology; D003868:Dequalinium / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology; D008969:Molecular Sequence Data; D010944:Plants / Q000201:enzymology / Q000648:ultrastructure; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011796:Quinacrine; D011797:Quinacrine Mustard / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D013572:Synaptic Vesicles / Q000201:enzymology; D014617:Vacuoles / Q000201:enzymology*
D002412:Cations; D011797:Quinacrine Mustard; D003868:Dequalinium; D006180:Proton-Translocating ATPases; D011796:Quinacrine; D004229:Dithiothreitol; D002746:Chlorpromazine