The cytochrome bc complex inhibitor Ametoctradin has an unusual binding mode.

Ametoctradin is an agricultural fungicide that selectively inhibits the cytochrome bc complex of oomycetes. Previous spectrophotometric studies using the purified cytochrome bc complex from Pythium sp. showed that Ametoctradin binds to the Q-site of the enzyme. However, as modeling studies suggested a binding mode like that of the substrate ubiquinol, the possibility for a dual Q- and Qi-site binding mode was left open. In this work, binding studies and enzyme assays with mitochondrial membrane preparations from Pythium sp. and an S. cerevisiae strain with a modified Q-site were used to investigate further the binding mode of Ametoctradin. The results obtained argue that the compound could bind to both the Q- and Qi-sites of the cytochrome bc complex and that its position or binding pose in the Q-site differs from that of Cyazofamid and Amisulbrom, the two Q-site-targeting, anti-oomycetes compounds. Furthermore, the data support the argument that Ametoctradin prefers binding to the reduced cytochrome bc complex. Thus, Ametoctradin has an unusual binding mode and further studies with this compound may offer the opportunity to better understand the catalytic cycle of the cytochrome bc complex.