Carbamoyl-Phosphate Synthase 1 as a Novel Target of Phomoxanthone A, a Bioactive Fungal Metabolite
Autor: | Sara Ceccacci, Jana Deitersen, Matteo Mozzicafreddo, Elva Morretta, Peter Proksch, Sebastian Wesselborg, Björn Stork, Maria Chiara Monti |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: | |
Zdroj: | Biomolecules, Vol 10, Iss 6, p 846 (2020) |
Druh dokumentu: | article |
ISSN: | 2218-273X |
DOI: | 10.3390/biom10060846 |
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: | Directory of Open Access Journals |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |
Pro tento záznam nejsou dostupné žádné jednotky.