The effects of exchange-inert metal-nucleotide complexes on the kinetics of beef heart mitochondrial F1-ATPase.
The inhibition of beef heart mitochondrial F1 by exchange-inert metal-nucleotide complexes was examined. Mono- and bidentate Cr(NH3)4ATP were found to be mixed noncompetitive inhibitors of F1-catalyzed ATP hydrolysis (values of Ki = 0.5 and 0.1 mM; values of alpha = 0.2 and 24, respectively). Rh(H2O)nATP was also found to be a mixed noncompetitive inhibitor of F1-catalyzed ATP hydrolysis (Ki = 0.3 mM, alpha = 0.7). These compounds were used in a series of dual inhibition experiments, along with mono- and bidentate CrATP and Co(NH3)4ATP. All the exchange-inert metal-nucleotides examined were found to be mutually exclusive inhibitors of F1, indicating that they all bind to the same site(s). It is postulated that the pKa of the metal-coordinated ligands is related to the potency of inhibition by these compounds. It appears probable that the exchange-inert nucleotide complexes are binding to site(s) in addition to the catalytic site(s) of F1.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D007700:Kinetics; D008929:Mitochondria, Heart / Q000201:enzymology*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D012238:Rhodium / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000255:Adenosine Triphosphate; D012238:Rhodium; D006180:Proton-Translocating ATPases