Inhibitors of a Na-pumping NADH-ubiquinone oxidoreductase play multiple roles to block enzyme function.

The Na-pumping NADH-ubiquinone (UQ) oxidoreductase (Na-NQR) is present in the respiratory chain of many pathogenic bacteria and is thought to be a promising antibiotic target. Whereas many details of Na-NQR structure and function are known, the mechanisms of action of potent inhibitors is not well-understood; elucidating the mechanisms would not only advance drug design strategies but might also provide insights on a terminal electron transfer from riboflavin to UQ. To this end, we performed photoaffinity labeling experiments using photoreactive derivatives of two known inhibitors, aurachin and korormicin, on isolated Na-NQR.