THE 49-KDA SUBUNIT OF NADH-UBIQUINONE OXIDOREDUCTASE (COMPLEX-I) IS INVOLVED IN THE BINDING OF PIERICIDIN AND ROTENONE, 2 QUINONE-RELATED INHIBITORS

Piericidin is a potent inhibitor of the mitochondrial and bacterial ty pe I NADH-ubiquinone oxidoreductases (Complex I) and is considered to bind at or close to the ubiquinone binding site(s) of the enzyme. Pier icidin-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,vith this resistance. B ased on this original observation, we propose a model locating the bin ding site for piericidin (and quinone) at the interface between the hy drophilic and hydrophobic domains of Complex I. (C) 1998 Federation of European Biochemical Societies.