3U6K

Ef-tu (escherichia coli) in complex with nvp-ldk733

Summary for 3U6K

• Entry DOI: 10.2210/pdb3u6k/pdb
• Related: 3U2Q 3U6B
• Related PRD ID: PRD_001073
• Descriptor: Elongation factor Tu 1, Thiocillin GE2270 analogue NVP-LDK733, 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: 4
• Total formula weight: 90471.24

Authors

Palestrant, D.J. (deposition date: 2011-10-12, release date: 2012-02-08, Last modification date: 2023-11-15)

Primary citation

LaMarche, M.J.,Leeds, J.A.,Amaral, K.,Brewer, J.T.,Bushell, S.M.,Dewhurst, J.M.,Dzink-Fox, J.,Gangl, E.,Goldovitz, J.,Jain, A.,Mullin, S.,Neckermann, G.,Osborne, C.,Palestrant, D.,Patane, M.A.,Rann, E.M.,Sachdeva, M.,Shao, J.,Tiamfook, S.,Whitehead, L.,Yu, D.
Antibacterial optimization of 4-aminothiazolyl analogues of the natural product GE2270 A: identification of the cycloalkylcarboxylic acids.
J.Med.Chem., 54:8099-8109, 2011

PubMed Abstract: 4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for their activity against Gram positive bacterial infections. Optimization efforts focused on improving the physicochemical properties (e.g., aqueous solubility and chemical stability) of the 4-aminothiazolyl natural product template while improving the in vitro and in vivo antibacterial activity. Structure-activity relationships were defined, and the solubility and efficacy profiles were improved over those of previous analogues and 1. These studies identified novel, potent, soluble, and efficacious elongation factor-Tu inhibitors, which bear cycloalkylcarboxylic acid side chains, and culminated in the selection of development candidates amide 48 and urethane 58.

PubMed: 21999529
DOI: 10.1021/jm200938f

Experimental method

X-RAY DIFFRACTION (2.45 Å)