The effect of binding of chlorpromazine and chloroquine to ion transporting ATPases

The inhibition of ion transporting ATPases (Na+,K+-ATPase, Ca2+,Mg2+- and C a2+-ATPase) by two amphiphilic drugs e.g. chlorpromazine (antipsychotic) an d chloroquine (antimalarial) are found to be competitive in nature in vitro with respect to the substrate. Two binding sites - high and low affinity a re found to exist on all the three ATPases toward these drugs as evident fr om the plot of F/F-0 vs. different drug concentrations of tryptophan fluore scence of the enzymes. Circular dichroism analysis suggest that binding of drugs to the high affinity site does not involve any change in conformation of ATPase molecules which occur only when drug binds to the low affinity s ites. The drug binding sites and possible effect on conformational change o f ATPase molecules of these two drugs have been described in this report.