4FN5

ELONGATION FACTOR G 1 (PSEUDOMONAS AERUGINOSA) IN COMPLEX WITH Argyrin B

4FN5 の概要

• エントリーDOI: 10.2210/pdb4fn5/pdb
• 分子名称: Elongation factor G 1, Argyrin B (3 entities in total)
• 機能のキーワード: elongation factor, translation, translation-antibiotic complex, translation/antibiotic
• 由来する生物種: Pseudomonas aeruginosa; 詳細
• 細胞内の位置: Cytoplasm (By similarity): Q9HWD2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 79035.60

構造登録者

Kirby, C.A.,Palestrant, D. (登録日: 2012-06-19, 公開日: 2012-09-26, 最終更新日: 2024-07-10)

主引用文献

Nyfeler, B.,Hoepfner, D.,Palestrant, D.,Kirby, C.A.,Whitehead, L.,Yu, R.,Deng, G.,Caughlan, R.E.,Woods, A.L.,Jones, A.K.,Barnes, S.W.,Walker, J.R.,Gaulis, S.,Hauy, E.,Brachmann, S.M.,Krastel, P.,Studer, C.,Riedl, R.,Estoppey, D.,Aust, T.,Movva, N.R.,Wang, Z.,Salcius, M.,Michaud, G.A.,McAllister, G.,Murphy, L.O.,Tallarico, J.A.,Wilson, C.J.,Dean, C.R.
Identification of elongation factor g as the conserved cellular target of argyrin B.
Plos One, 7:e42657-e42657, 2012

PubMed Abstract: Argyrins, produced by myxobacteria and actinomycetes, are cyclic octapeptides with antibacterial and antitumor activity. Here, we identify elongation factor G (EF-G) as the cellular target of argyrin B in bacteria, via resistant mutant selection and whole genome sequencing, biophysical binding studies and crystallography. Argyrin B binds a novel allosteric pocket in EF-G, distinct from the known EF-G inhibitor antibiotic fusidic acid, revealing a new mode of protein synthesis inhibition. In eukaryotic cells, argyrin B was found to target mitochondrial elongation factor G1 (EF-G1), the closest homologue of bacterial EF-G. By blocking mitochondrial translation, argyrin B depletes electron transport components and inhibits the growth of yeast and tumor cells. Further supporting direct inhibition of EF-G1, expression of an argyrin B-binding deficient EF-G1 L693Q variant partially rescued argyrin B-sensitivity in tumor cells. In summary, we show that argyrin B is an antibacterial and cytotoxic agent that inhibits the evolutionarily conserved target EF-G, blocking protein synthesis in bacteria and mitochondrial translation in yeast and mammalian cells.

PubMed: 22970117
DOI: 10.1371/journal.pone.0042657

実験手法

X-RAY DIFFRACTION (2.9 Å)