Probing binding determinants in center P of the cytochrome bc(1) complex using novel hydroxy-naphthoquinones.

ABSTRACT: Atovaquone is a substituted 2-hydroxy-naphthoquinone used therapeutically against Plasmodium falciparum (malaria) and Pneumocystis pathogens. It acts by inhibiting the cytochrome bc(1) complex via interactions with the Rieske iron-sulfur protein and cytochrome b in the ubiquinol oxidation pocket. As the targeted pathogens have developed resistance to this drug there is an urgent need for new alternatives. To better understand the determinants of inhibitor binding in the ubiquinol oxidation pocket of the bc(1) complex we synthesized a series of hydroxy-naphthoquinones bearing a methyl group on the benzene ring that is predicted to interact with the nuclear encoded Rieske iron-sulfur protein. We have also attempted to overcome the metabolic instability of a potent cytochrome bc(1) complex in

SUBMITTER: Hughes LM 

PROVIDER: S-EPMC2787711 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature