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 (QP) and the quinone reduction (QN) center. These sites can be distinguished by the specific binding of inhibitors to either of them. A substantial body of information about the hydroquinone oxidation site has been provided by the analysis of the binding of QP site inhibitors to the bc1 complex in different redox states and to preparations depleted of lipid or protein components as well as by functional studies with mutant bc1 complexes selected for resistance toward the inhibitors. The reaction site is formed by at least five protein segments of cytochrome b and parts of the iron-sulfur protein. At least two different binding sites for QP site inhibitors could be detected, one for the methoxyacrylate-type inhibitors binding predominantly to cytochrome b, the other for the chromone-type inhibitors and hydroxyquinones binding predominantly to the iron-sulfur protein. The interactions with the protein segments, between different protein segments, and between protein and ligands (substrate, inhibitors) are discussed in detail and a working model of the QP pocket is proposed.
Universitätsklinikum Frankfurt/Main, Germany.
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D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D004579:Electron Transport / Q000187:drug effects; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010084:Oxidation-Reduction; D017354:Point Mutation; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011809:Quinones / Q000378:metabolism; D016992:Rhodobacter / Q000201:enzymology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship
D001426:Bacterial Proteins; D005656:Fungal Proteins; D007506:Iron-Sulfur Proteins; D011809:Quinones; C037989:Rieske iron-sulfur protein; D014450:Electron Transport Complex III