Phomoxanthone A Targets ATP Synthase.
Rameez AliSangram S ParelkarPaul R ThompsonSusan Mitroka-BatsfordSiddartha YerramilliSuzanne F ScarlataKatelyn S MistrettaJeannine M CoburnAnita E MattsonPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2022)
Phomoxanthone A is a naturally occurring molecule and a powerful anti-cancer agent, although its mechanism of action is unknown. To facilitate the determination of its biological target(s), we used affinity-based labelling using a phomoxanthone A probe. Labelled proteins were pulled down, subjected to chemoproteomics analysis using LC-MS/MS and ATP synthase was identified as a likely target. Mitochondrial ATP synthase was validated in cultured cells lysates and in live intact cells. Our studies show sixty percent inhibition of ATP synthase by 260 μM phomoxanthone A.