S279 point mutations in Candida albicans Sterol 14-α demethylase (CYP51) reduce in vitro inhibition by fluconazole.

ABSTRACT: The effects of S279F and S279Y point mutations in Candida albicans CYP51 (CaCYP51) on protein activity and on substrate (lanosterol) and azole antifungal binding were investigated. Both S279F and S279Y mutants bound lanosterol with 2-fold increased affinities (K(s), 7.1 and 8.0 μM, respectively) compared to the wild-type CaCYP51 protein (K(s), 13.5 μM). The S279F and S279Y mutants and the wild-type CaCYP51 protein bound fluconazole, voriconazole, and itraconazole tightly, producing typical type II binding spectra. However, the S279F and S279Y mutants had 4- to 5-fold lower affinities for fluconazole, 3.5-fold lower affinities for voriconazole, and 3.5- to 4-fold lower affinities for itraconazole than the wild-type CaCYP51 protein. The S279F and S279Y mutants gave 2.3- and 2.8-fold higher 5

SUBMITTER: Warrilow AG 

PROVIDER: S-EPMC3318376 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature