3u2q

EF-Tu (Escherichia coli) in complex with NVP-LFF571

spinqualitylabelsall models 3u2q, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3u2q is a 2 chain structure with sequence from Escherichia coli k-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GDP, MG NonStd Res: 7BB, BB6, BB7, BB8, BB9, MEN, MH6 Related: 3u6k, 3u6b Gene: tufA, b3339, JW3301 (Escherichia coli K-12) Resources: FirstGlance, OCA, RCSB, PDBsum Function [EFTU1_ECOLI] This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.[HAMAP-Rule:MF_00118] May play an important regulatory role in cell growth and in the bacterial response to nutrient deprivation.[HAMAP-Rule:MF_00118] [THCL_PLARO] Has bacteriocidal activity against Gram-positive bacteria and a few Gram-negative bacteria. It is particularly active against anaerobes. Inhibits bacterial protein biosynthesis by preventing the formation of a stable complex between the elongation factor Tu (EF-Tu), GTP and tRNA, hindering the activation of EF-Tu. Publication Abstract from PubMed Clostridium difficile (C. difficile) is a Gram positive, anaerobic bacterium that infects the lumen of the large intestine and produces toxins. This results in a range of syndromes from mild diarrhea to severe toxic megacolon and death. Alarmingly, the prevalence and severity of C. difficile infection are increasing; thus, associated morbidity and mortality rates are rising. 4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for the treatment of C. difficile infection. The medicinal chemistry effort focused on enhancing aqueous solubility relative to that of the natural product and previous development candidates (2, 3) and improving antibacterial activity. Structure-activity relationships, cocrystallographic interactions, pharmacokinetics, and efficacy in animal models of infection were characterized. These studies identified a series of dicarboxylic acid derivatives, which enhanced solubility/efficacy profile by several orders of magnitude compared to previously studied compounds and led to the selection of LFF571 (4) as an investigational new drug for treating C. difficile infection. Discovery of LFF571: an investigational agent for Clostridium difficile infection.,LaMarche MJ, Leeds JA, Amaral A, Brewer JT, Bushell SM, Deng G, Dewhurst JM, Ding J, Dzink-Fox J, Gamber G, Jain A, Lee K, Lee L, Lister T, McKenney D, Mullin S, Osborne C, Palestrant D, Patane MA, Rann EM, Sachdeva M, Shao J, Tiamfook S, Trzasko A, Whitehead L, Yifru A, Yu D, Yan W, Zhu Q J Med Chem. 2012 Mar 8;55(5):2376-87. Epub 2012 Feb 23. PMID:22315981 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Elongation factor

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