Saccharomyces cerevisiae-based mutational analysis of the bc1 complex Qo site residue 279 to study the trade-off between atovaquone resistance and function.

ABSTRACT: The bc1 complex is central to mitochondrial bioenergetics and the target of the antimalarial drug atovaquone that binds in the quinol oxidation (Qo) site of the complex. Structural analysis has shown that the Qo site residue Y279 (Y268 in Plasmodium falciparum) is key for atovaquone binding. Consequently, atovaquone resistance can be acquired by mutation of that residue. In addition to the probability of amino acid substitution, the level of atovaquone resistance and the loss of bc1 complex activity that are associated with the novel amino acid would restrict the nature of resistance-driven mutations occurring on atovaquone exposure in native parasite populations. Using the yeast model, we characterized the effect of all the amino acid replacements resulting from a single nucleotide substi

SUBMITTER: Song Z 

PROVIDER: S-EPMC4468654 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature