3U2Q
EF-Tu (Escherichia coli) in complex with NVP-LFF571
Summary for 3U2Q
| Entry DOI | 10.2210/pdb3u2q/pdb |
| Related | 3U6B 3U6K |
| Related PRD ID | PRD_001072 |
| Descriptor | Elongation factor Tu 1, Thiocillin GE2270 analogue NVP-LFF571, GUANOSINE-5'-DIPHOSPHATE, ... (5 entities in total) |
| Functional Keywords | translation factor-antibiotic complex, translation factor/antibiotic |
| Biological source | Escherichia coli |
| Cellular location | Cytoplasm: P0CE47 Secreted: Q7M0J8 |
| Total number of polymer chains | 2 |
| Total formula weight | 45335.74 |
| Authors | Palestrant, D.J. (deposition date: 2011-10-04, release date: 2012-05-02, Last modification date: 2023-11-15) |
| Primary citation | 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 Cited by 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: 22315981DOI: 10.1021/jm201685h PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
Download full validation report
