Specificities of the two center N inhibitors of mitochondial bc1 complex, antimycin and funiculosin: strong involvement of cytochrome b-asparagine-208 in funiculosin binding.
Funiculosin, a center N inhibitor of the bc1 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 bc1 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 (QN).
Brasseur
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Bioénergétique et Ingénierie des Protéines, C.N.R.S., Marseille, France.
Brivet-Chevillotte
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D000880:Anthraquinones / Q000378:metabolism / Q000494:pharmacology; D000935:Antifungal Agents / Q000378:metabolism*; D000968:Antimycin A / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D001216:Asparagine / Q000502:physiology; D001665:Binding Sites; D003573:Cytochrome b Group / Q000737:chemistry / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013053:Spectrophotometry; D013696:Temperature
D000880:Anthraquinones; D000935:Antifungal Agents; D003573:Cytochrome b Group; C032456:antimycin; C015286:funiculosin (anthraquinone); D000968:Antimycin A; D001216:Asparagine; D014450:Electron Transport Complex III