Ptilomycalin A, a novel Na+, K(+)- or Ca2(+)-ATPase inhibitor, competitively interacts with ATP at its binding site.
Ptilomycalin A inhibited the brain Na+, K(+)-ATPase and Ca2(+)-ATPase from skeletal sarcoplasmic reticulum with an IC50 value of 2 microM and 10 microM, respectively. Kinetic analysis of the inhibitory effects of ptilomycalin A suggests that the inhibition of Na+, K(+)-ATPase is a competitive-, an uncompetitive- and an anticompetitive-type with respect to ATP, Na+ and K+, respectively. The inhibition of Ca2(+)-ATPase by ptilomycalin A is a competitive- or an uncompetitive-type with respect to ATP or Ca2+, respectively. These results suggest that ptilomycalin A interacts with ATP at the ATP binding site of Na+, K(+)-ATPase or Ca2(+)-ATPase. Ptilomycalin A has become a useful biochemical tool for clarifying the ATP binding site in both enzymes.
Ohizumi
Y
Y
Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Sasaki
S
S
Kusumi
T
T
Ohtani
I I
II
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006146:Guanidines; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D000470:Alkaloids; D006146:Guanidines; C103200:ptilomycalin A; D000255:Adenosine Triphosphate; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase