Abstract
CYP51 (Erg11) belongs to the cytochrome P450 monooxygenase (CYP) superfamily and mediates a crucial step of the synthesis of ergosterol, which is a fungal-specific sterol. It is also the target of azole drugs in clinical practice. In recent years, researches on fungal CYP51 have stepped into a new stage attributing to the discovery of crystal structures of the homologs in Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. This review summarizes the functions, structures of fungal CYP51 proteins, and the inhibitors targeting these homologs. In particular, several drug-resistant mechanisms associated with the fungal CYP51s are introduced. The sequences and crystal structures of CYP51 proteins in different fungal species are also compared. These will provide new insights for the advancement of research on antifungal agents.
Highlights
The incidence of invasive fungal infections has increased during the past three decades, arising more and more concern
Together with information from the analysis of multiplesequence alignment of CYP51 proteins from human and fungi including S. cerevisiae, C. albicans, C. glabrata, C. tropicalis, C. krusei, C. dubliniensis, C. parapsilosis, A. fumigatus and Cryptococcus neoformans showing that the identity varied between 36.5 and 93.9% among them (Table 1)
CYP51 point mutation plays an important role in pan-azole resistance of C. auris
Summary
The incidence of invasive fungal infections has increased during the past three decades, arising more and more concern. Together with information from the analysis of multiplesequence alignment of CYP51 proteins from human and fungi including S. cerevisiae, C. albicans, C. glabrata, C. tropicalis, C. krusei, C. dubliniensis, C. parapsilosis, A. fumigatus and Cryptococcus neoformans showing that the identity varied between 36.5 and 93.9% among them (Table 1). Transcription factors of non-pathogenic species may bring some information, such as Set4 in S. cerevisiae, which represses CYP51 expression and reduces drug resistance (Serratore et al, 2018).
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