ArticlePloS one2014
Cytochrome P450 monooxygenase CYP53 family in fungi: comparative structural and evolutionary analysis and its role as a common alternative anti-fungal drug target.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 80 citations in OpenAlex.
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- Consensus scoring-guided virtual screening identifies potent anti-saprolegniasis compounds targeting a P450 fusion protein.Frontiers in microbiology · 2025Article
- Genome analysis of the esca-associated Basidiomycetes Fomitiporia mediterranea, Fomitiporia polymorpha, Inonotus vitis, and Tropicoporus texanus reveals virulence factor repertoires characteristic of white-rot fungi.G3 (Bethesda, Md.) · 2024Article
- Structure-Function Analysis of the EssentialInternational journal of molecular sciences · 2024Article
- Structure-Function Analysis of the Biotechnologically Important Cytochrome P450 107 (CYP107) Enzyme Family.Biomolecules · 2023Article
- Genome-Wide Analysis of the Cytochrome P450 Monooxygenases in the Lichenized Fungi of the ClassMicroorganisms · 2023Article
- Pezizomycetes Genomes Reveal Diverse P450 Complements Characteristic of Saprotrophic and Ectomycorrhizal Lifestyles.Journal of fungi (Basel, Switzerland) · 2023Article
- Complete genome analysis of pathogenic Metschnikowia bicuspidata strain MQ2101 isolated from diseased ridgetail white prawn, Exopalaemon carinicauda.BMC microbiology · 2023Article
- Article
- Saprophytic to Pathogenic Mycobacteria: Loss of Cytochrome P450s Vis a Vis Their Prominent Involvement in Natural Metabolite Biosynthesis.International journal of molecular sciences · 2022Article
- An Unprecedented Number of Cytochrome P450s Are Involved in Secondary Metabolism inMicroorganisms · 2022Article
- Genomic Studies of White-Rot FungusJournal of fungi (Basel, Switzerland) · 2021Article
- In Silico Structural Modeling and Analysis of Interactions ofInternational journal of molecular sciences · 2021Article
- Ancient Bacterial ClassInternational journal of molecular sciences · 2021Article
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytochrome P450 monooxygenases (CYPs/P450s) are heme-thiolate proteins whose role as a drug target against pathogenic microbes has been explored because of their stereo- and regio-specific oxidation activity. We aimed to assess the CYP53 family's role as a common alternative drug target against animal (including human) and plant pathogenic fungi and its role in fungal-mediated wood degradation. Genome-wide analysis of fungal species revealed the presence of CYP53 members in ascomycetes and basidiomycetes. Basidiomycetes had a higher number of CYP53 members in their genomes than ascomycetes. Only two CYP53 subfamilies were found in ascomycetes and six subfamilies in basidiomycetes, suggesting that during the divergence of phyla ascomycetes lost CYP53 P450s. According to phylogenetic and gene-structure analysis, enrichment of CYP53 P450s in basidiomycetes occurred due to the extensive duplication of CYP53 P450s in their genomes. Numerous amino acids (103) were found to be conserved in the ascomycetes CYP53 P450s, against only seven in basidiomycetes CYP53 P450s. 3D-modelling and active-site cavity mapping data revealed that the ascomycetes CYP53 P450s have a highly conserved protein structure whereby 78% amino acids in the active-site cavity were found to be conserved. Because of this rigid nature of ascomycetes CYP53 P450s' active site cavity, any inhibitor directed against this P450 family can serve as a common anti-fungal drug target, particularly toward pathogenic ascomycetes. The dynamic nature of basidiomycetes CYP53 P450s at a gene and protein level indicates that these P450s are destined to acquire novel functions. Functional analysis of CYP53 P450s strongly supported our hypothesis that the ascomycetes CYP53 P450s ability is limited for detoxification of toxic molecules, whereas basidiomycetes CYP53 P450s play an additional role, i.e. involvement in degradation of wood and its derived components. This study is the first report on genome-wide comparative structural (gene and protein structure-level) and evolutionary analysis of a fungal P450 family.
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