Lanosterol 14-alpha demethylase (CYP51) (ERG11)

Lanosterol 14-alpha demethylase, frequently designated as Erg11p in fungal species, is a key enzyme in the biosynthesis of ergosterol, which is the primary sterol found in fungal cell membranes (UniProt P43084). As a member of the cytochrome P450 superfamily, specifically CYP51, it catalyzes the essential oxidative removal of the 14-alpha-methyl group from lanosterol or eburicol (PubMed 10428669). Ergosterol is crucial for maintaining the structural integrity, fluidity, and function of the fungal plasma membrane, serving a role analogous to cholesterol in mammalian cells. This enzyme is the primary therapeutic target for the azole class of antifungal drugs, including fluconazole and voriconazole (StatPearls NBK500030). These drugs bind to the heme iron within the enzyme's active site, effectively blocking its catalytic activity. The resulting depletion of ergosterol and the accumulation of toxic 14-alpha-methylated sterol precursors lead to severe membrane stress and fungal growth inhibition. However, the clinical utility of targeting Erg11p is often complicated by the development of resistance through point mutations in the ERG11 gene and the potential for significant drug-drug interactions due to the inhibition of host cytochrome P450 enzymes (PubMed 28634317).

Other names

Erg11pCytochrome P450 51Sterol 14-alpha demethylaseLanosterol 14-alpha-methyl demethylaseCYP51F1

Inhibition of lanosterol 14-alpha demethylase by binding to the heme iron atom, which prevents the conversion of lanosterol to ergosterol, leading to membrane dysfunction.