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
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