UK-2A,B,C and D, novel antifungal antibiotics from Streptomyces sp.517.02. V. Inhibition mechanism of bovine heart mitochondrial cytochrome bc1 by the novel antibiotic UK-2A.
UK-2A is a potent antifungal antibiotic isolated from Streptomyces sp. 517-02 and its structure is highly similar to that of antimycin A. We investigated the inhibition mechanism of bovine heart mitochondrial cytochrome bc1 complex by the UK-2A using antimycin A and myxothiazol as the reference inhibitors of ubiquinol oxidation (Qo) and ubiquinone reduction (Qi) sites, respectively. The inhibitory potency of UK-2A was about 3-fold less than antimycin A. On the basis of the effects of UK-2A on the reduction kinetics of b and c1 hemes, this compound appeared to be an inhibitor of the Qi site. However, since spectral changes of dithionite-reduced cytochrome b induced by UK-2A binding differed from that of antimycin A, the precise binding manner of UK-2A to the enzyme is not identical to that of antimycin A. It could be concluded that antimycin A binding to cytochrome b is primarily decided by structural specificity of the salicylic acid moiety.
Machida
K
K
Department of Biology, Graduate School of Science, Osaka City University, Osaka, Japan.
Takimoto
H
H
Miyoshi
H
H
Taniguchi
M
M
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007783:Lactones / Q000378:metabolism / Q000494:pharmacology; D008689:Methacrylates; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology; D013302:Streptomyces / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology
D000935:Antifungal Agents; D007783:Lactones; D008689:Methacrylates; D011725:Pyridines; D013844:Thiazoles; C101439:UK 2A; C101494:UK 2B; C101495:UK 2C; C101496:UK 2D; C030517:myxothiazol; D014450:Electron Transport Complex III