Evidence for a quinone binding site close to the interface between NUOD and NUOB subunits of Complex I.
Piericidin, rotenone and pyridaben are specific inhibitors of the NADH-ubiquinone oxidoreductase (Complex I) that bind to its ubiquinone binding site(s). Using site directed mutagenesis, we demonstrate that residues G409, D412, R413 and V407 of the C-terminus of Complex I NUOD subunit are directly involved in the binding of these inhibitors. We propose that the corresponding inhibitor/quinone binding site would be located close to NUOD-NUOB interface.
Laboratoire de Bioénergétique Cellulaire et Pathologique (EA 2943-UJF), Département de Biologie Moléculaire et Structurale CEA Grenoble, 17 rue des Martyrs, 38054 Cedex 9, Grenoble, France. iprieur@cea.fr
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Prieur
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Lunardi
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Dupuis
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003001:Cloning, Molecular; D042967:Electron Transport Complex I; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019920:Photoaffinity Labels; D011725:Pyridines / Q000494:pharmacology; D011809:Quinones / Q000378:metabolism*; D016354:Rhodobacter capsulatus; D012402:Rotenone / Q000494:pharmacology; D016415:Sequence Alignment
D004791:Enzyme Inhibitors; D019920:Photoaffinity Labels; D011725:Pyridines; D011809:Quinones; D012402:Rotenone; C100213:piericidin A; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I