Carbamoyl-phosphate synthase 1 as a novel target of phomoxanthone a, a bioactive fungal metabolite
| Autor: | Sebastian Wesselborg, Matteo Mozzicafreddo, Peter Proksch, Jana Deitersen, Björn Stork, Sara Ceccacci, Elva Morretta, Maria Chiara Monti |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Proteomics
Bioactive xanthone Cellular respiration Proteolysis Xanthones Carbamoyl-Phosphate Synthase (Ammonia) lcsh:QR1-502 Phomopsis Targeted-limited proteolysis Mitochondrion 010402 general chemistry 01 natural sciences Biochemistry Article lcsh:Microbiology 03 medical and health sciences chemistry.chemical_compound Xanthone medicine Humans Drug affinity responsive target stability Molecular docking Molecular Biology 030304 developmental biology 0303 health sciences medicine.diagnostic_test ATP synthase biology Chemistry Ligand (biochemistry) Electron transport chain 0104 chemical sciences Molecular Docking Simulation Mechanism of action biology.protein medicine.symptom HeLa Cells |
| Zdroj: | Biomolecules, Vol 10, Iss 846, p 846 (2020) Biomolecules Volume 10 Issue 6 |
| Popis: | Phomoxanthone A, a bioactive xanthone dimer isolated from the endophytic fungus Phomopsis sp., is a mitochondrial toxin weakening cellular respiration and electron transport chain activity by a fast breakup of the mitochondrial assembly. Here, a multi-disciplinary strategy has been developed and applied for identifying phomoxanthone A target(s) to fully address its mechanism of action, based on drug affinity response target stability and targeted limited proteolysis. Both approaches point to the identification of carbamoyl-phosphate synthase 1 as a major phomoxanthone A target in mitochondria cell lysates, giving also detailed insights into the ligand/target interaction sites by molecular docking and assessing an interesting phomoxanthone A stimulating activity on carbamoyl-phosphate synthase 1. Thus, phomoxanthone A can be regarded as an inspiring molecule for the development of new leads in counteracting hyperammonemia states. |
| Databáze: | OpenAIRE |
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