The 49-kDa subunit of NADH-ubiquinone oxidoreductase (Complex I) is involved in the binding of piericidin and rotenone, two quinone-related inhibitors.
Piericidin is a potent inhibitor of the mitochondrial and bacterial type I NADH-ubiquinone oxidoreductases (Complex I) and is considered to bind at or close to the ubiquinone binding site(s) of the enzyme. Piericidin-resistant mutants of the bacterium Rhodobacter capsulatus have been isolated and the present work demonstrates that a single missense mutation at the level of the gene encoding the peripheral 49-kDa/NUOD subunit of Complex I is definitely associated with this resistance. Based on this original observation, we propose a model locating the binding site for piericidin (and quinone) at the interface between the hydrophilic and hydrophobic domains of Complex I.
Laboratoire de Bioénergétique Cellulaire et Pathologique, (EA 2411-UJF), Départment de Biologie Moléculaire et Structurale CEA Grenoble, France.
E
E
Darrouzet
J P
JP
Issartel
J
J
Lunardi
A
A
Dupuis
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D004352:Drug Resistance, Microbial; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology; D011809:Quinones / Q000737:chemistry; D016354:Rhodobacter capsulatus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D012402:Rotenone / Q000378:metabolism / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011725:Pyridines; D011809:Quinones; D012402:Rotenone; C100213:piericidin A; D016660:NAD(P)H Dehydrogenase (Quinone)