5JBQ

EF-TU (ESCHERICHIA COLI) IN COMPLEX WITH THIOMURACIN ANALOG

Summary for 5JBQ

• Entry DOI: 10.2210/pdb5jbq/pdb
• Descriptor: Elongation factor Tu 1, THIOMURACIN ANALOG, GUANOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: natural product inhibitor, elongation factor, rna binding protein-antimicrobial complex, rna binding protein/antimicrobial
• Biological source: Escherichia coli (strain K12); More
• Cellular location: Cytoplasm: P0CE47
• Total number of polymer chains: 2
• Total formula weight: 45432.04

Authors

Palestrant, D.,Stams, T. (deposition date: 2016-04-13, release date: 2016-07-13, Last modification date: 2023-11-15)

Primary citation

LaMarche, M.J.,Leeds, J.A.,Brewer, J.,Dean, K.,Ding, J.,Dzink-Fox, J.,Gamber, G.,Jain, A.,Kerrigan, R.,Krastel, P.,Lee, K.,Lombardo, F.,McKenney, D.,Neckermann, G.,Osborne, C.,Palestrant, D.,Patane, M.A.,Rann, E.M.,Robinson, Z.,Schmitt, E.,Stams, T.,Tiamfook, S.,Yu, D.,Whitehead, L.
Antibacterial and Solubility Optimization of Thiomuracin A.
J.Med.Chem., 59:6920-6928, 2016

PubMed Abstract: Synthetic studies of the antimicrobial secondary metabolite thiomuracin A (1) provided access to analogues in the Northern region (C2-C10). Selective hydrolysis of the C10 amide of lead compound 2 and subsequent derivatization led to novel carbon- and nitrogen-linked analogues (e.g., 3) which improved antibacterial potency across a panel of Gram-positive organisms. In addition, congeners with improved physicochemical properties were identified which proved efficacious in murine sepsis and hamster C. difficile models of disease. Optimal efficacy in the hamster model of C. difficile was achieved with compounds that possessed both potent antibacterial activity and high aqueous solubility.

PubMed: 27355833
DOI: 10.1021/acs.jmedchem.6b00726

Experimental method

X-RAY DIFFRACTION (2.006 Å)