Lanosterol 14-alpha demethylase (Malassezia globosa) (CYP51)

Lanosterol 14-alpha demethylase (CYP51) is a critical cytochrome P450 enzyme in the fungal pathogen Malassezia globosa, where it catalyzes the essential conversion of lanosterol into ergosterol (UniProt: A8Q6Q1). Ergosterol is a vital component of the fungal cell membrane, maintaining its structural integrity and fluidity, much like cholesterol in animal cells (PubMed: 18258910). In Malassezia globosa, this enzyme is a primary therapeutic target for treating conditions such as dandruff, seborrheic dermatitis, and pityriasis versicolor (PubMed: 17978868). Azole antifungal agents, such as ketoconazole and itraconazole, bind to the heme iron within the enzyme's active site, effectively inhibiting its catalytic activity (PubChem: CID 3823). This inhibition leads to the depletion of ergosterol and the accumulation of toxic methylated sterol precursors, resulting in impaired membrane function and fungal growth inhibition (StatPearls: NBK459130). Understanding the specific structure of M. globosa CYP51 is crucial for developing more selective and potent antifungal treatments with reduced side effects.

Other names

Cytochrome P450 51CYP51Sterol 14-alpha demethylaseErg1114-alpha-demethylase

Inhibition of the enzyme prevents the conversion of lanosterol to ergosterol, leading to the accumulation of toxic 14-alpha-methyl sterols and depletion of ergosterol, which disrupts fungal cell membrane integrity (PubMed: 18258910).