title: Mucidin and strobilurin A are identical and inhibit electron transfer in the cytochrome bc1 complex of the mitochondrial respiratory chain at the same site as myxothiazol.
abstract: Mucidin and strobilurin A, antifungal antibiotics isolated from the basidiomycetes Oudemansiella mucida and Strobiluris tenacellus, respectively, inhibit electron-transfer reactions in the cytochrome bc1 complex of the mitochondrial respiratory chain. The two compounds have identical effects on oxidation-reduction reactions of the cytochromes b and c1 in isolated succinate-cytochrome c reductase. They inhibit reduction of cytochrome c1 by succinate but do not inhibit reduction of cytochrome b. When added in combination with antimycin, either inhibitor blocks reduction of both cytochromes b and c1. Mucidin and strobilurin A differ from antimycin in that they inhibit, rather than promote, oxidant-induced reduction of cytochrome b. They also differ from antimycin in that they do not block reduction of cytochrome b by succinate when cytochrome c1 is previously reduced by ascorbate and they do not inhibit oxidation of cytochrome b by fumarate. These effects of mucidin and strobilurin A are, however, qualitatively identical with those of myxothiazol, an antibiotic that inhibits respiration by binding to cytochrome b [Von Jagow, G., Ljungdahl, P. O., Graf, P., Ohnishi, T., & Trumpower, B. L. (1984) J. Biol. Chem. 259, 6319-6326]. Mucidin and strobilurin A have identical UV and mass spectra, and they elute together on high-pressure liquid chromatography. We thus conclude that these antibiotics, although isolated from different bacteria, are structurally identical. Our results indicate that strobilurin A and mucidin inhibit electron transport at the same site as myxothiazol and not at the antimycin site, as previously reported [Subik, J., Behren, M., & Musilek, V. (1974) Biochem. Biophys. Res. Commun. 57, 17-22].
mesh_terms: D000475:Alkenes / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D004579:Electron Transport / Q000187:drug effects; D014450:Electron Transport Complex III; D005231:Fatty Acids, Unsaturated; D007700:Kinetics; D013058:Mass Spectrometry; D008689:Methacrylates; D008928:Mitochondria / Q000201:enzymology*; D009097:Multienzyme Complexes / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011485:Protein Binding; D011808:Quinone Reductases / Q000378:metabolism*; D000073739:Strobilurins; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D000475:Alkenes; D000935:Antifungal Agents; D005231:Fatty Acids, Unsaturated; D008689:Methacrylates; D009097:Multienzyme Complexes; D000073739:Strobilurins; D013844:Thiazoles; C008556:mucidin; C030517:myxothiazol; D011808:Quinone Reductases; D014450:Electron Transport Complex III