ArticleThe Journal of biological chemistry2015
Structure-Functional Characterization of Cytochrome P450 Sterol 14α-Demethylase (CYP51B) from Aspergillus fumigatus and Molecular Basis for the Development of Antifungal Drugs.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- Updating genome annotation for the microbial cell factory Aspergillus niger using gene co-expression networks.Nucleic acids research · 2019Pooled it
- Computational Discovery of Novel CYP51 Inhibitors for Antifungal Therapy Against Aspergillus fumigatus.Probiotics and antimicrobial proteins · 2026Article
- Benzophenone Derivatives as a New Class of Anti-Infectives Against Acanthamoeba spp.Archiv der Pharmazie · 2026Article
- Article
- The dual role of azoles: lifesaving antifungals and drivers of resistance - a One Health perspective.Nature communications · 2026Review
- Prevalence of cyp51A variants in a US collection of Aspergillus fumigatus clinical isolates and comparative analysis of their contribution to triazole antifungal resistance.The Journal of antimicrobial chemotherapy · 2026Article
- Rising antifungal resistance inFrontiers in microbiology · 2026Review
- Molecular modeling studies, in vitro antioxidant and antimicrobial assay and BSA affinity of novel benzyl-amine derived scaffolds as CYP51B inhibitors.Molecular diversity · 2025Article
- No Evidence for Environmental Triazole Resistance Selection Route in Aspergillus Section Flavi, The Netherlands, 1994-2023.Mycopathologia · 2025Article
- Unique Structural Features Relate to Evolutionary Adaptation of Cytochrome P450 in the Abyssal Zone.International journal of molecular sciences · 2025Article
- Design and Synthesis of Thymol Derivatives Bearing a 1,2,3-Triazole Moiety for Papaya Protection againstJournal of agricultural and food chemistry · 2025Article
- Progress and Prospects of Triazoles in Advanced Therapies for Parasitic Diseases.Tropical medicine and infectious disease · 2025Review
- Activity of Azole and Non-Azole Substances AgainstInternational journal of molecular sciences · 2025Article
- Computational analysis of Ayurvedic metabolites for potential treatment of drug-resistantFrontiers in cellular and infection microbiology · 2025Article
- Article
- Exploring the Molecular Mechanisms of Resistance to Prochloraz byJournal of fungi (Basel, Switzerland) · 2024Article
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- Mechanism of the Oxidative Ring-Closure Reaction during Gliotoxin Biosynthesis by Cytochrome P450 GliF.International journal of molecular sciences · 2024Article
- Design and Synthesis of Eugenol Derivatives Bearing a 1,2,3-Triazole Moiety for Papaya Protection againstJournal of agricultural and food chemistry · 2024Article
- Identification of Potent and Selective Inhibitors ofJournal of medicinal chemistry · 2024Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Aspergillus fumigatus is the opportunistic fungal pathogen that predominantly affects the immunocompromised population and causes 600,000 deaths/year. The cytochrome P450 51 (CYP51) inhibitor voriconazole is currently the drug of choice, yet the treatment efficiency remains low, calling for rational development of more efficient agents. A. fumigatus has two CYP51 genes, CYP51A and CYP51B, which share 59% amino acid sequence identity. CYP51B is expressed constitutively, whereas gene CYP51A is reported to be inducible. We expressed, purified, and characterized A. fumigatus CYP51B, including determination of its substrate preferences, catalytic parameters, inhibition, and x-ray structure in complexes with voriconazole and the experimental inhibitor (R)-N-(1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide (VNI). The enzyme demethylated its natural substrate eburicol and the plant CYP51 substrate obtusifoliol at steady-state rates of 17 and 16 min(-1), respectively, but did not metabolize lanosterol, and the topical antifungal drug miconazole was the strongest inhibitor that we identified. The x-ray crystal structures displayed high overall similarity of A. fumigatus CYP51B to CYP51 orthologs from other biological kingdoms but revealed phylum-specific differences relevant to enzyme catalysis and inhibition. The complex with voriconazole provides an explanation for the potency of this relatively small molecule, whereas the complex with VNI outlines a direction for further enhancement of the efficiency of this new inhibitory scaffold to treat humans afflicted with filamentous fungal infections.
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