Stereo-selective interaction of enantiomers of diniconazole, a fungicide, with purified P-450/14DM from yeast.
R(-) isomer of diniconazole [S-3308L, (E)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1,2,4-triazol-l-yl)-1-+ ++penten-3-ol], a newly developed fungicide strongly inhibited lanosterol 14 alpha-demethylation catalyzed by a yeast cytochrome P-450 (P-450/14DM). On the other hand, S(+) isomer of diniconazole was a weaker inhibitor for P-450/14DM. The R(-) isomer combined with both ferric and ferrous P-450/14DM and interfered binding of CO to the cytochrome. The S(+) isomer also interacted with both forms of P-450/14DM but the absorption spectra of the S(+)-diniconazole complexes were different from those of the R(-)-diniconazole complexes. Furthermore, S(+) isomer did not significantly interfere the binding of CO to P-450/14DM. These observations suggest that P-450/14DM discriminates enantiomers of diniconazole and the R(-) isomer is more favorably fit for the active site of the cytochrome.
D000935:Antifungal Agents; D002248:Carbon Monoxide / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013057:Spectrum Analysis; D013237:Stereoisomerism; D058886:Sterol 14-Demethylase; D014230:Triazoles / Q000494:pharmacology*
D000935:Antifungal Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D014230:Triazoles; D002248:Carbon Monoxide; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase; C049346:diniconazole