ArticleScientific reports2016
Triazole resistance mediated by mutations of a conserved active site tyrosine in fungal lanosterol 14α-demethylase.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 111 citations in OpenAlex.
- Molecular Mechanisms, Diagnosis, and Therapeutic Strategies of Antifungal Resistance in Filamentous Fungi.Journal of fungi (Basel, Switzerland) · 2026Review
- Comparative Analysis of Virulence Traits and Fluconazole-Response Mechanisms in Clinical Isolates ofMicroorganisms · 2026Article
- The dual role of azoles: lifesaving antifungals and drivers of resistance - a One Health perspective.Nature communications · 2026Review
- A Retrospective, Comparative Cohort Analysis of the Utilization of Voriconazole-Containing Regimens Versus Itraconazole in the Treatment of Blastomycosis.Journal of fungi (Basel, Switzerland) · 2026Article
- The molecular basis of intrinsic resistance to azoles inAntimicrobial agents and chemotherapy · 2026Article
- Synthesis, Characterization, Density Functional Theory Calculation, In Silico and In Vitro Antimicrobial Evaluation of New 1,2,4-Triazole-Amide Conjugates.Chemistry & biodiversity · 2026Article
- Integrated In Silico and In Vitro Study of Copper Nanocatalyzed Carbonyl-Functionalized Triazoles-Inducing S Phase Cell Cycle Arrest and Apoptosis in MCF-7.ChemistryOpen · 2026Article
- Article
- Chromosomal-level assembly of Magnusiomyces clavatus: novel genetic insights on an emerging fungal pathogen.G3 (Bethesda, Md.) · 2025Article
- Dermatophyte-Selective Imidazole-Thiosemicarbazides: Potent In Vitro Activity AgainstInternational journal of molecular sciences · 2025Article
- FungAMR: a comprehensive database for investigating fungal mutations associated with antimicrobial resistance.Nature microbiology · 2025Article
- Exploring Long Arm Amide-Linked Side Chains in the Design of Antifungal Azole Inhibitors of Sterol 14α-Demethylase (CYP51).Journal of medicinal chemistry · 2025Article
- Exploring Novel Y140F/H Mutant Fungal CYP51 Inhibitors: A Molecular Docking and Dynamics Study on Thiophene Compounds.Journal of pharmacy & bioallied sciences · 2025Article
- Repurposing FDA-Approved Drugs for Eumycetoma Treatment: Homology Modeling and Computational Screening of CYP51 Inhibitors.International journal of molecular sciences · 2025Article
- Intrinsic resistance to short-tailed azoles in the basal fungusFrontiers in microbiology · 2025Article
- From crops to clinic: the impact of dual azole use on antifungal resistance inFrontiers in microbiology · 2025Review
- The Molecular Basis of the Intrinsic and Acquired Resistance to Azole Antifungals inJournal of fungi (Basel, Switzerland) · 2024Article
- Potent Antimicrobial Azoles: Synthesis, In Vitro and In Silico Study.Antibiotics (Basel, Switzerland) · 2024Article
- Effect of Conformational Variability on the Drug Resistance ofACS omega · 2024Article
- Molecular mechanisms that govern infection and antifungal resistance in Mucorales.Microbiology and molecular biology reviews : MMBR · 2024Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emergence of fungal strains showing resistance to triazole drugs can make treatment of fungal disease problematic. Triazole resistance can arise due to single mutations in the drug target lanosterol 14α-demethylase (Erg11p/CYP51). We have determined how commonly occurring single site mutations in pathogenic fungi affect triazole binding using Saccharomyces cerevisiae Erg11p (ScErg11p) as a target surrogate. The mutations Y140F/H were introduced into full-length hexahistidine-tagged ScErg11p. Phenotypes and high-resolution X-ray crystal structures were determined for the mutant enzymes complexed with short-tailed (fluconazole and voriconazole) or long-tailed (itraconazole and posaconazole) triazoles and wild type enzyme complexed with voriconazole. The mutations disrupted a water-mediated hydrogen bond network involved in binding of short-tailed triazoles, which contain a tertiary hydroxyl not present in long-tailed triazoles. This appears to be the mechanism by which resistance to these short chain azoles occurs. Understanding how these mutations affect drug affinity will aid the design of azoles that overcome resistance.
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