Inhibition of H+-transporting ATPase by formation of a tight nucleoside diphosphate-fluoroaluminate complex at the catalytic site.
Inhibition of the mitochondrial and bacterial F1-type ATPases [of ATP phosphohydrolase (H+-transporting), EC 3.6.1.34] by fluoride was found to depend on the presence of aluminum and ADP at the catalytic site(s) of F1-type ATPase. AIF-4 was demonstrated to be the active fluoroaluminate species. The identical pattern of inhibition of F1-type ATPase activity obtained in the presence of ADP and NaF with beryllium, a metal that forms fluoride complexes strictly tetracoordinated, suggests that aluminum acts through a tetrahedral complex. Inhibition of isolated F1-type ATPase by AIF-4 in the presence of ADP cannot be reversed by ADP, ATP, or chelators of aluminum. However, the inhibition of the ATPase activity of the F1 sector in submitochondrial particles caused by AIF-4 and ADP was reversed upon addition of an oxidizable substrate. Uncouplers prevented the reversal of inhibition, suggesting that the protonmotive force generated by respiration was responsible for the relief of inhibition. Because of structural similarities between AIF4- and , AIF4- is postulated to mimic the phosphate group of ATP and form an abortive complex with ADP at the active site(s) of F1-type ATPase.
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000535:Aluminum / Q000494:pharmacology*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D002712:Chlorides / Q000494:pharmacology*; D005461:Fluorine / Q000494:pharmacology*; D007700:Kinetics; D008929:Mitochondria, Heart / Q000201:enzymology; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D012969:Sodium Fluoride / Q000494:pharmacology*; D013367:Submitochondrial Particles / Q000201:enzymology
D017607:Aluminum Compounds; D002712:Chlorides; C053629:fluoroaluminum; D005461:Fluorine; D000077410:Aluminum Chloride; D000244:Adenosine Diphosphate; D012969:Sodium Fluoride; D000535:Aluminum; D006180:Proton-Translocating ATPases