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Phomoxanthone A Targets ATP Synthase.

Abstract
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.
AuthorsRameez Ali, Sangram S Parelkar, Paul R Thompson, Susan Mitroka-Batsford, Siddartha Yerramilli, Suzanne F Scarlata, Katelyn S Mistretta, Jeannine M Coburn, Anita E Mattson
JournalChemistry (Weinheim an der Bergstrasse, Germany) (Chemistry) Vol. 28 Issue 70 Pg. e202202397 (Dec 15 2022) ISSN: 1521-3765 [Electronic] Germany
PMID36082977 (Publication Type: Journal Article)
Copyright© 2022 Wiley-VCH GmbH.
Chemical References
  • phomoxanthone A
  • Mitochondrial Proton-Translocating ATPases
  • Affinity Labels
  • Adenosine Triphosphate
Topics
  • Chromatography, Liquid
  • Tandem Mass Spectrometry
  • Mitochondrial Proton-Translocating ATPases (metabolism)
  • Affinity Labels
  • Adenosine Triphosphate (metabolism)

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