The Formylamino Group of Antimycin is Essential in Specifically Inhibiting Cyclic Electron Transport.

Abstract

The antibiotic antimycin is a naturally occurring inhibitor of mitochondrial electron flow. Antimycin inhibits the cytochrome b/c complex by binding to the Q_i site and thereby blocking electron transfer from the heme b_H to ubiquinone. The antimycin A molecule consists of a dilactone ring (non-essential for activity) amide linked to a salicyl moiety with a formylamino group at position 3 (figure 1A). According to Miyoshi et al. (1) the conformation and bulkiness of the formylamino group is important for the binding of antimycin, while the acidity of the hydroxy group governs the degree of inhibition by the molecule. The hydrophobicity of the dilactone group is believed to aid in the penetration of the molecule into the membrane, and to facilitate the fitting of the salicyl moiety into the binding domain (1-4). Miyake et al (5) show that the dilactone group is involved in the hydrophobic binding of antimycin to a low-potential cytochrome b ₅₅₉ in maize thylakoids, while the hydrogen bonding by the formylamino group is necessary for inhibition of photoreduction of this cytochrome.