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Inhibitory Mechanisms of Antibiotics Targeting Elongation Factor Tu

[ Vol. 3 , Issue. 1 ]

Author(s):

T. Hogg, J. R. Mesters and R. Hilgenfeld   Pages 121 - 131 ( 11 )

Abstract:


Since the pioneering discovery of the inhibitory effects of kirromycin on bacterial elongation factor Tu (EF-Tu) more than 25 years ago [1], a great wealth of biological data has accumulated concerning protein biosynthesis inhibitors specific for EF-Tu. With the subsequent discovery of over two dozen naturally occurring EF-Tu inhibitors belonging to four different subclasses, EF-Tu has blossomed into an appealing antimicrobial target for rational drug discovery efforts. Very recently, independent crystal structure determinations of EF-Tu in complex with two potent antibiotics, aurodox and GE2270A, have provided structural explanations for the mode of action of these two compounds, and have set the foundation for the design of inhibitors with higher bioavailability, broader spectra, and greater efficacy.

Keywords:

Inhibitory Mechanisms, Antibiotics Targeting Elongation Factor Tu, thermus thermophilus, the kirromycine, pulvomycin, cyclic thiazolyls, enacyloxin lla, planobispora rosea cinnamoneus, nocardialactamdurans, streptomyces, ramocissimus

Affiliation:

Department of Structural Biology and Crystallography, Institute of Molecular Biotechnology, Beutenbergstrasse 11, D-07745 Jena, Germany



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