SPECIFICITIES OF THE 2 CENTER N-INHIBITORS OF MITOCHONDRIAL BC(1) COMPLEX, ANTIMYCIN AND FUNICULOSIN - STRONG INVOLVEMENT OF CYTOCHROME-B ASPARAGINE-208 IN FUNICULOSIN BINDING

Funiculosin, a center N inhibitor of the bc(1) complex, induces a blue-shift in the cytochrome b spectrum. A thermosensitive revertant [Coppee, J.Y. et al., J. Biol. Chem. 269 (1994) 4221-4226] isolated from a cytochrome b respiratory-deficient mutant, exhibits a red-shift instead of the blue-shift retained in the original mutant and shows resistance to this inhibitor. Replacing cytochrome b-Asparagine-208 by Lysine in this revertant, keeping the original mutation S206L, leads, when mitochondria are incubated at non-permissive temperature, to complete loss of be, complex activity and funiculosin-binding, while the antimycin-binding is conserved. These data suggest some inhibitor site specificity and close proximity between the funiculosin-binding site and the catalytic center N domain (Q(N)).