4fn5

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

spinqualitylabelsall models 4fn5, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4fn5 is a 2 chain structure with sequence from Actinoplanes sp. and Pseudomonas aeruginosa PAO1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Ligands: 0UO, BB9, DAL, DBB, DHA, SAR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function EFG1_PSEAE Catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome.[HAMAP-Rule:MF_00054] Publication Abstract from PubMed 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. Identification of elongation factor g as the conserved cellular target of argyrin B.,Nyfeler B, Hoepfner D, Palestrant D, Kirby CA, Whitehead L, Yu R, Deng G, Caughlan RE, Woods AL, Jones AK, Barnes SW, Walker JR, Gaulis S, Hauy E, Brachmann SM, Krastel P, Studer C, Riedl R, Estoppey D, Aust T, Movva NR, Wang Z, Salcius M, Michaud GA, McAllister G, Murphy LO, Tallarico JA, Wilson CJ, Dean CR PLoS One. 2012;7(9):e42657. Epub 2012 Sep 10. PMID:22970117 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Elongation factor 3D structures

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