The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors

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 s...

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Autores principales: Zhang, Jingxiang, Li, Liping, Lv, Quanzhen, Yan, Lan, Wang, Yan, Jiang, Yuanying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Microbiology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491756/
https://www.ncbi.nlm.nih.gov/pubmed/31068906
http://dx.doi.org/10.3389/fmicb.2019.00691
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author Zhang, Jingxiang
Li, Liping
Lv, Quanzhen
Yan, Lan
Wang, Yan
Jiang, Yuanying
author_facet Zhang, Jingxiang
Li, Liping
Lv, Quanzhen
Yan, Lan
Wang, Yan
Jiang, Yuanying
author_sort Zhang, Jingxiang
collection PubMed
description 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.
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spelling pubmed-64917562019-05-08 The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors Zhang, Jingxiang Li, Liping Lv, Quanzhen Yan, Lan Wang, Yan Jiang, Yuanying Front Microbiol Microbiology 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. Frontiers Media S.A. 2019-04-24 /pmc/articles/PMC6491756/ /pubmed/31068906 http://dx.doi.org/10.3389/fmicb.2019.00691 Text en Copyright © 2019 Zhang, Li, Lv, Yan, Wang and Jiang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Zhang, Jingxiang
Li, Liping
Lv, Quanzhen
Yan, Lan
Wang, Yan
Jiang, Yuanying
The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors
title The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors
title_full The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors
title_fullStr The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors
title_full_unstemmed The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors
title_short The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors
title_sort fungal cyp51s: their functions, structures, related drug resistance, and inhibitors
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491756/
https://www.ncbi.nlm.nih.gov/pubmed/31068906
http://dx.doi.org/10.3389/fmicb.2019.00691
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