Cited by 459Antifungal resistance and susceptibilityFungal Plant Pathogen ControlMicrobial Natural Products and Biosynthesis

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Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis

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Hargrove, Tatiana Y., Friggeri, Laura, Wawrzak, Zdzislaw, Qi, Aidong, Hoekstra, William J., Schotzinger, Robert J., York, John D., Guengerich, F. Peter, Lepesheva, Galina I.·2017·Journal of Biological Chemistry

DOI 10.1074/jbc.m117.778308PMC PMC5399120

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Abstract

With some advances in modern medicine (such as cancer chemotherapy, broad exposure to antibiotics, and immunosuppression), the incidence of opportunistic fungal pathogens such as Candida albicans has increased. Cases of drug resistance among these pathogens have become more frequent, requiring the development of new drugs and a better understanding of the targeted enzymes. Sterol 14α-demethylase (CYP51) is a cytochrome P450 enzyme required for biosynthesis of sterols in eukaryotic cells and is the major target of clinical drugs for managing fungal pathogens, but some of the CYP51 key features important for rational drug design have remained obscure. We report the catalytic properties, ligand-binding profiles, and inhibition of enzymatic activity of C. albicans CYP51 by clinical antifungal drugs that are used systemically (fluconazole, voriconazole, ketoconazole, itraconazole, and posaconazole) and topically (miconazole and clotrimazole) and by a tetrazole-based drug candidate, VT-1161 (oteseconazole: ( R )-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1 H -tetrazol-1-yl)-1-(5-(4-(2,2,2-trifluoroethoxy)phenyl)pyridin-2-yl)propan-2-ol). Among the compounds tested, the first-line drug fluconazole was the weakest inhibitor, whereas posaconazole and VT-1161 were the strongest CYP51 inhibitors. We determined the X-ray structures of C. albicans CYP51 complexes with posaconazole and VT-1161, providing a molecular mechanism for the potencies of these drugs, including the activity of VT-1161 against Candida krusei and Candida glabrata , pathogens that are intrinsically resistant to fluconazole. Our comparative structural analysis outlines phylum-specific CYP51 features that could direct future rational development of more efficient broad-spectrum antifungals.

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UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 45,882
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 29,915
Hidden Killers: Human Fungal Infections
Brown, G. D., Denning, D. W., Gow, N. A. R., Levitz, S. M., Netea, M. G., & White, T. C. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004404 · Cited by 4,284
Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America
Pappas, P. G., Kauffman, C. A., Andes, D. R., Clancy, C. J., Marr, K. A., Ostrosky-Zeichner, L., Reboli, A. C., Schuster, M. G., Vazquez, J. A., Walsh, T. J., et al. (2016) · Clinical Infectious Diseases · doi:10.1093/cid/civ933 · Cited by 4,200
Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensions
Krissinel, E., & Henrick, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904026460 · Cited by 3,788
Clinical Practice Guidelines for the Management Candidiasis: 2009 Update by the Infectious Diseases Society of America
Pappas, P. G., Kauffman, C. A., Andes, D., Benjamin, D. K., Calandra, T. F., Edwards, J. E., Filler, S. G., Fisher, J. F., Kullberg, B.-J., Zeichner, L. O., et al. (2009) · Clinical Infectious Diseases · doi:10.1086/596757 · Cited by 3,191
Cytochrome P-450: Structure, Mechanism, and Biochemistry
de Montellano, O., & Paul, R. (1986) · Medical Entomology and Zoology · Cited by 2,663
Cytochrome P450: Structure, mechanism, and biochemistry
PRYOR, W. A. (1996) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(96)83807-x · Cited by 1,603
Clinical, Cellular, and Molecular Factors That Contribute to Antifungal Drug Resistance
White, T. C., Marr, K. A., & Bowden, R. A. (1998) · Clinical Microbiology Reviews · doi:10.1128/cmr.11.2.382 · Cited by 1,353
The Catalytic Pathway of Cytochrome P450cam at Atomic Resolution
Schlichting, I., Berendzen, J., Chu, K., Stock, A., Maves, S. A., Benson, D. E., Sweet, R. M., Ringe, D., Petsko, G. A., & Sligar, S. G. (2000) · Science · doi:10.1126/science.287.5458.1615 · Cited by 1,349

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Formation and Cleavage of C–C Bonds by Enzymatic Oxidation–Reduction Reactions
Guengerich, F. P., & Yoshimoto, F. K. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00031 · Cited by 298
Self-citation
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Shafiei, M., Peyton, L., Hashemzadeh, M., & Foroumadi, A. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.104240 · Cited by 295
The Fungal CYP51s: Their Functions, Structures, Related Drug Resistance, and Inhibitors
Zhang, J., Li, L., Lv, Q., Yan, L., Wang, Y., & Jiang, Y. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00691 · Cited by 261
Current treatment options for vulvovaginal candidiasis caused by azole-resistant Candida species
Sobel, J. D., & Sobel, R. (2018) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1476490 · Cited by 168
A comprehensive overview of the medicinal chemistry of antifungal drugs: perspectives and promise
Howard, K. C., Dennis, E. K., Watt, D. S., & Garneau‐Tsodikova, S. (2020) · Chemical Society Reviews · doi:10.1039/c9cs00556k · Cited by 149
Fungal Lanosterol 14α-demethylase: A target for next-generation antifungal design
Monk, B. C., Sagatova, A. A., Hosseini, P., Ruma, Y. N., Wilson, R. K., & Keniya, M. V. (2019) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2019.02.008 · Cited by 148
Emerging New Targets for the Treatment of Resistant Fungal Infections
Liu, N., Tu, J., Dong, G., Wang, Y., & Sheng, C. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01413 · Cited by 129
Antifungals and Drug Resistance
Hossain, C. M., Ryan, L. K., Gera, M., Choudhuri, S., Lyle, N., Ali, K. A., & Diamond, G. (2022) · Encyclopedia · doi:10.3390/encyclopedia2040118 · Cited by 135
CYP51 as drug targets for fungi and protozoan parasites: past, present and future
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Self-citation
The Role of Ergosterol and Sphingolipids in the Localization and Activity of Candida albicans’ Multidrug Transporter Cdr1p and Plasma Membrane ATPase Pma1p
Urbanek, A. K., Muraszko, J., Derkacz, D., Łukaszewicz, M., Bernat, P., & Krasowska, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179975 · Cited by 26
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Oteseconazole: First Approved Orally Bioavailable and Selective CYP51 Inhibitor for the Treatment of Patients with Recurrent Vulvovaginal Candidiasis
De, S. K. (2023) · Current Medicinal Chemistry · doi:10.2174/0929867330666230220130024 · Cited by 24

Authors: Hargrove, T. Y., Friggeri, L., Wawrzak, Z., Qi, A., Hoekstra, W. J., Schotzinger, R. J., York, J. D., Guengerich, F. P., & Lepesheva, G. I.
Affiliations: Vanderbilt University (US)
Northwestern University (US)
Viamet Pharmaceuticals (United States) (US)
Corresponding author: Lepesheva, Galina I.
ORCID: Wawrzak, Zdzislaw
York, John D.
Guengerich, F. Peter
Lepesheva, Galina I.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2017-04
Volume: 292
Issue: 16
Pages: 6728-6743
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m117.778308
PMC: PMC5399120
OpenAlex: W2593598577
Cited by: 444
References: 57
Citations by year: 2026: 67 · 2025: 82 · 2024: 49 · 2023: 64 · 2022: 55 · 2021: 30 · 2020: 39 · 2019: 25 · 2018: 24 · 2017: 9
FWCI: 21.04
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 1243 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (R01 GM067871)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Agricultural and Biological Sciences › Plant Science › Fungal Plant Pathogen Control
Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Microbial Natural Products and Biosynthesis
Keywords: Candida albicans, sterol 14α-demethylase, CYP51, cytochrome P450, azole antifungals, posaconazole, oteseconazole, fluconazole, ketoconazole, voriconazole, itraconazole, miconazole, clotrimazole, fungal sterol biosynthesis, drug resistance, Candida krusei, Candida glabrata, X-ray crystal structure, ligand binding, antifungal drug design
MeSH terms: Animals, Antifungal Agents, Azoles, Candida albicans, Crystallization, Fungal Proteins, Heme, Humans, Kinetics, Ligands, Microbial Sensitivity Tests, Protein Binding, Protein Conformation, Protons, Sterols, Rats, Sterol 14-Demethylase

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Structural analyses of Candida albicans sterol 14α-demethylase complexed with azole drugs address the molecular basis of azole-mediated inhibition of fungal sterol biosynthesis

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