Inhibition of ATPase activity of Escherichia coli ATP synthase by polyphenols

We have studied the inhibitory effect of five polyphenols namely, resveratrol, piceatannol, quercetin, quercetrin, and quercetin-3-beta-D glucoside on Escherichia coli ATP synthase. Recently published X-ray crystal structures of bovine mitochondrial ATP synthase inhibited by resveratrol, piceatannol, and quercetin, suggest that these compounds bind in a hydrophobic pocket between the gamma-subunit C-terminal tip and the hydrophobic inside of the surrounding annulus in a region critical for rotation of the gamma-subunit. Herein, we show that resveratrol, piceatannol, quercetin, quercetrin, or quercetin-3-beta-D glucoside all inhibit E. coli ATP synthase but to different degrees. Whereas piceatannol inhibited ATPase essentially completely (similar to 0 residual activity), inhibition by other compounds was partial with similar to 20% residual activity by quercetin, similar to 50% residual activity by quercetin-3-beta-D glucoside, and similar to 60% residual activity by quercetrin or resveratrol. Piceatannol was the most potent inhibitor (IC50 similar to 14 mu M) followed by quercetin (IC50 similar to 33 mu M), quercetin-3-beta-D glucoside (IC50 similar to 71 mu M), resveratrol (IC50 similar to 94 mu M), quercitrin (IC50 similar to 120 mu M). Inhibition was identical in both F1Fo. membrane preparations as well as in isolated purified F-1. In all cases inhibition was reversible. Interestingly, resveratrol and piceatannol inhibited both ATPase and ATP synthesis whereas quercetin, quercetrin or quercetin-3-beta-D glucoside inhibited only ATPase activity and not ATP synthesis. (C) 2009 Elsevier B.V. All rights reserved.