In:
Biomolecules, MDPI AG, Vol. 10, No. 6 ( 2020-06-02), p. 846-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
2218-273X
DOI:
10.3390/biom10060846
Language:
English
Publisher:
MDPI AG
Publication Date:
2020
detail.hit.zdb_id:
2701262-1
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