Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

The natural product argyrin B inhibits bacteria and eukaryotic cell growth by inhibition of elongation factor G1.

Nyfeler, Beat and Hoepfner, Dominic and Palestrant, Deborah and Kirby, Christina and Whitehead, Lewis and Yu, Robert and Deng, Gejing and Caughlan, Ruth and Woods, Angela and Jones, Adriana and Barnes, Whitney and Walker, John and Gaulis, Swann and Hauy, Ervan and Brachmann, Saskia and Krastel, Philipp and Studer, Christian and Riedl, Ralph and Estoppey, David and Aust, Thomas and Movva, Rao and Wang, Zuncai and Salcius, Michael and Michaud, Gregory and Mcallister, Gregory and Murphy, Leon and Tallarico, John and Wilson, Christopher and Myer, Vic and Dean, Charles (2012) The natural product argyrin B inhibits bacteria and eukaryotic cell growth by inhibition of elongation factor G1. PLoS ONE, 7 (9). pp. 1-12. ISSN 1932-6203

Abstract

Argyrins are cyclic octapeptides that have antibacterial, immunosuppressive and antitumor activity. Using bacterial mutant selection and whole genome sequencing, we identified elongation factor G (EF-G) as the cellular target of argyrin B. Purified EF-G bound argyrin tightly, and the co-crystal structure of EF-G in complex with argyrin B revealed a novel binding pocket that was clearly delineated by the locations of resistance determining amino acid subtitutions. In eukaryotic cells, argyrin B was found to inhibit mitochondrial elongation factor G1 (a close homologue of EF-G), thereby blocking mitochondrial translation, depleting electron transport components, and inhibiting the growth of rapidly dividing tumor cells. This study identifies argyrin B as an antibacterial and cytotoxic agent that inhibits EF-G, a target which is evolutionarily conserved from bacteria to yeast to mammalian cells.

Item Type: Article
Related URLs:
Additional Information: Can archive pre-print and post-print or publisher's version/PDF
Keywords: argyrin natural product antibacterial elongation factor G cytotoxicity mitochondria
Related URLs:
Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/6511

Search

Email Alerts

Register with OAK to receive email alerts for saved searches.