bc1 complex activity and sensitivity to Qo site inhibitors.

The mutated residues in the yeast strains are presented in Table 2 for the Plasmodium-like mutants (PF) and in Table 3 for the human-like mutants (HS). Their location in the sequence and the structure is shown in Fig. 1.TN, turnover number: cytochrome c reduced per bc1 complex per second (Materials and Methods). The values are presented as % of the WT activity (140 s−1).IC50, mid-point inhibition concentration.The IC50 values for bovine and yeast enzymes were obtained as described in Materials and Methods. The values are presented as ratio of IC50 on the concentration of monomeric bc1 complex (estimated using cytochrome optical signal as in Materials and Methods). For example, 4 molecules of atovaquone were added per yeast WT monomeric bc1 complex to inhibit the quinol cytochrome c reductase activity by 50%.For P. falciparum enzyme, the atovaquone IC50 is taken from [21]. In the same study, the IC50s for bovine and human enzymes were approximately 70 nM. The RCQ06 IC50value is from [14]. Note that the bc1 complex concentrations in the P. falciparum preparations used for inhibitor titrations were not available in the published studies. It was thus not possible to present the data as the molar ratio IC50/[bc1 complex]. An IC50 of azoxystrobin is not available. The inhibitor was reported to be highly active on the parasite growth [8].