Molecular basis for resistance to myxothiazol, mucidin (strobilurin A), and stigmatellin. Cytochrome b inhibitors acting at the center o of the mitochondrial ubiquinol-cytochrome c reductase in Saccharomyces cerevisiae

• Published in: The Journal of biological chemistry Vol. 264; no. 24; pp. 14543 - 14548
• Main Authors: DI RAGO, J.-P, COPPEE, J.-Y, COLSON, A.-M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 25.08.1989
• Subjects: Action of physical and chemical agents; Amino Acid Sequence - drug effects; Antifungal Agents - pharmacology; Base Composition - drug effects; Biological and medical sciences; Cytochrome b Group - antagonists & inhibitors; Cytochrome b Group - genetics; DNA, Mitochondrial - drug effects; Drug Resistance, Microbial; Electron Transport Complex III - antagonists & inhibitors; Electron Transport Complex III - genetics; Fundamental and applied biological sciences. Psychology; Methacrylates; Microbiology; Molecular Sequence Data; Mutation; Mycology; Oxygen Consumption - drug effects; Polyenes - pharmacology; Saccharomyces cerevisiae; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Sequence Homology, Nucleic Acid; Thiazoles - pharmacology; Cytochrome; Electron transfer; Hemoprotein; Yeast; Mutation
• ISSN: 0021-9258; 1083-351X

The respiratory bc1 complex transfers the electrons from ubiquinol to cytochrome c oxidase. Myxothiazol, strobilurin A (mucidin), and stigmatellin are center o inhibitors preventing electron transfer at the ubiquinone redox site Qo, which is located closer to the outer side of the inner mitochondrial membrane. The cytochrome b gene is carried by the organelle DNA. Yeast mutants resistant to myxothiazol and mucidin have been previously isolated and mapped to specific loci of the cytochrome b gene. In the present work, stigmatellin-resistant mutants were isolated and genetically analyzed. The mutated amino acid residues from seven myxothiazol-, four mucidin-, and six stigmatellin-resistant mutants have been identified by sequencing the relevant segments of the resistant cytochrome b gene. A third myxothiazol-resistant locus and the first stigmatellin-resistant locus were identified. The mutated codons were found to be clustered in two regions of the cytochrome b protein which appeared to be responsible for the resistance to Qo site inhibitors. The first region is within the end of the first, the second, and the beginning of the third exon whereas the second region is within exon five and the beginning of the sixth exon.