Fungal cytochrome P450 lanosterol 14-α-demethylase (CYP51 (also Erg11 in yeast/fungi))

Fungal cytochrome P450 lanosterol 14-α-demethylase (CYP51) is a membrane-bound enzyme that catalyzes the removal of the 14α-methyl group from lanosterol, a key step in the biosynthesis of ergosterol, the principal sterol and structural component of fungal plasma membranes. CYP51 belongs to the conserved cytochrome P450 superfamily and is highly specific for its sterol substrates. The integrity of ergosterol is crucial for fungal cell membrane permeability, fluidity, and survival. Azole antifungal drugs selectively inhibit CYP51 by binding the heme iron in the enzyme's active site, thus blocking ergosterol synthesis and leading to fungal cell death. Resistance can arise through mutations in the enzyme or increased drug efflux. CYP51 is present in all biological kingdoms, but the fungal version is the primary therapeutic target in medicine and agriculture for the treatment and prophylaxis of diverse fungal infections

Other names

Lanosterol 14α-demethylaseCYP51Erg11 (specifically in Saccharomyces cerevisiae and other fungal species)Sterol 14-demethylaseP45014DM

Inhibition of lanosterol 14-α-demethylase blocks conversion of lanosterol to ergosterol, disrupting fungal membrane structure and function\nAzole antifungals coordinate to the heme iron in the enzyme's active site, directly inhibiting catalysis