Thymoquinone Inhibits Escherichia coli ATP Synthase and Cell Growth

We examined the thymoquinone induced inhibition of purified F(1) or membrane bound F(1)F(O) E. coli ATP synthase. Both purified F(1) and membrane bound F(1)F(O) were completely inhibited by thymoquinone with no residual ATPase activity. The process of inhibition was fully reversible and identical in both membrane bound F(1)F(o) and purified F(1) preparations. Moreover, thymoquinone induced inhibition of ATP synthase expressing wild-type E. coli cell growth and non-inhibition of ATPase gene deleted null control cells demonstrates that ATP synthase is a molecular target for thymoquinone. This also links the beneficial dietary based antimicrobial and anticancer effects of thymoquinone to its inhibitory action on ATP synthase.