Open AccessY132H substitution in Candida albicans sterol 14α‐demethylase confers fluconazole resistance by preventing binding to haem
Author(s) -
Kelly Steven L,
Lamb David C,
Kelly Diane E
Publication year - 1999
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1111/j.1574-6968.1999.tb08792.x
Subject(s) - fluconazole , ergosterol , sterol , azole , candida albicans , mutant , biochemistry , biology , corpus albicans , wild type , lanosterol , chemistry , microbiology and biotechnology , antifungal , gene , cholesterol
Abstract Fungal cytochrome P450 sterol 14α‐demethylase (CYP51) is required for ergosterol biosynthesis and is the target for azole antifungal compounds. The amino acid substitution Y132H in CYP51 from clinical isolates of Candida albicans can cause fluconazole resistance by a novel change in the protein. Fluconazole binding to the mutant protein did not involve normal interaction with haem as shown by inducing a Type I spectral change. This contrasted to the wild‐type protein where fluconazole inhibition was reflected in coordination to haem as a sixth ligand and where the typical Type II spectrum was obtained. The Y132H substitution occurred without drastic perturbation of the haem environment or activity allowing resistant mutants to produce ergosterol and retain fitness, an efficient strategy for resistance in nature.