WHAT INFORMATION DO INHIBITORS PROVIDE ABOUT THE STRUCTURE OF THE HYDROQUINONE OXIDATION SITE OF UBIHYDROQUINONE - CYTOCHROME-C OXIDOREDUCTASE

The Q cycle mechanism of the bc1 complex requires two quinone reaction centers, the hydroquinone oxidation (Q(P)) and the quinone reduction (Q(N)) center. These sites can be distinguished by the specific bindin g of inhibitors to either of them. A substantial body of information a bout the hydroquinone oxidation site has been provided by the analysis of the binding of Q(P) site inhibitors to the bc1 complex in differen t redox states and to preparations depleted of lipid or protein compon ents as well as by functional studies with mutant bc1 complexes select ed for resistance toward the inhibitors. The reaction site is formed b y at least five protein segments of cytochrome b and parts of the iron -sulfur protein. At least two different binding sites for Q(P) site in hibitors could be detected, one for the methoxyacrylate-type inhibitor s binding predominantly to cytochrome b, the other for the chromone-ty pe inhibitors and hydroxyquinones binding predominantly to the iron-su lfur protein. The interactions with the protein segments, between diff erent protein segments, and between protein and ligands (substrate, in hibitors) are discussed in detail and a working model of the Q(P) pock et is proposed.