3U2Q

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

3U2Q の概要

• エントリーDOI: 10.2210/pdb3u2q/pdb
• 関連するPDBエントリー: 3U6B 3U6K
• 関連するBIRD辞書のPRD_ID: PRD_001072
• 分子名称: Elongation factor Tu 1, Thiocillin GE2270 analogue NVP-LFF571, GUANOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: translation factor-antibiotic complex, translation factor/antibiotic
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm: P0CE47; Secreted: Q7M0J8
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 45335.74

構造登録者

Palestrant, D.J. (登録日: 2011-10-04, 公開日: 2012-05-02, 最終更新日: 2023-11-15)

主引用文献

LaMarche, M.J.,Leeds, J.A.,Amaral, A.,Brewer, J.T.,Bushell, S.M.,Deng, G.,Dewhurst, J.M.,Ding, J.,Dzink-Fox, J.,Gamber, G.,Jain, A.,Lee, K.,Lee, L.,Lister, T.,McKenney, D.,Mullin, S.,Osborne, C.,Palestrant, D.,Patane, M.A.,Rann, E.M.,Sachdeva, M.,Shao, J.,Tiamfook, S.,Trzasko, A.,Whitehead, L.,Yifru, A.,Yu, D.,Yan, W.,Zhu, Q.
Discovery of LFF571: an investigational agent for Clostridium difficile infection.
J.Med.Chem., 55:2376-2387, 2012

PubMed Abstract: 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.

PubMed: 22315981
DOI: 10.1021/jm201685h

実験手法

X-RAY DIFFRACTION (2.7 Å)