Nyfeler, Beat, Hoepfner, Dominic, Palestrant, Deborah, Kirby, Christina, Whitehead, Lewis, Yu, Robert, Deng, Gejing, Caughlan, Ruth, Woods, Angela, Jones, Adriana, Barnes, Whitney, Walker, John, Gaulis, Swann, Hauy, Ervan, Brachmann, Saskia, Krastel, Philipp, Studer, Christian, Riedl, Ralph, Estoppey, David, Aust, Thomas, Movva, Rao, Wang, Zuncai, Salcius, Michael, Michaud, Gregory, Mcallister, Gregory, Murphy, Leon, Tallarico, John, Wilson, Christopher, 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:	http://www.ncbi.nlm.nih.gov/pubmed/22970...
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:	http://www.ncbi.nlm.nih.gov/pubmed/22970...
Date Deposited:	13 Oct 2015 13:14
Last Modified:	13 Oct 2015 13:14
URI:	https://oak.novartis.com/id/eprint/6511