Lanosterol 14-alpha-demethylase (Saccharomyces cerevisiae) (Erg11p)

Lanosterol 14-alpha-demethylase, commonly known as Erg11p in Saccharomyces cerevisiae, is a vital cytochrome P450 enzyme essential for the biosynthesis of ergosterol, the primary sterol in fungal cell membranes [UniProt P10614]. It catalyzes the oxidative removal of the 14-alpha-methyl group from lanosterol, a rate-limiting step in the production of ergosterol which maintains membrane fluidity and integrity [PubMed 10831452]. This enzyme serves as the principal target for azole antifungal agents, such as fluconazole and voriconazole, which coordinate with the heme iron in the enzyme's active site to block substrate binding [PubChem CID 3365]. The resulting depletion of ergosterol and accumulation of toxic 14-alpha-methylated sterols disrupt the fungal cell membrane, leading to growth inhibition [PubMed 25730362]. Although S. cerevisiae is a non-pathogenic yeast, Erg11p is highly homologous to the CYP51 enzymes in pathogenic fungi like Candida albicans, making it a cornerstone of antifungal drug development and resistance research [PubMed 11714470].

Other names

CYP51Cytochrome P450 51Lanosterol 14-demethylaseERG11Sterol 14-alpha-demethylaseCytochrome P450 51 (Saccharomyces cerevisiae)

Inhibition of lanosterol 14-alpha-demethylase by binding to the heme iron atom within the enzyme's active site, preventing the conversion of lanosterol to ergosterol and leading to membrane dysfunction.