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FEBS Lett. 2006 Aug 21;580(19):4576-81. Epub 2006 Jul 24.

Elongation factor Tu-targeted antibiotics: four different structures, two mechanisms of action.

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Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10 C, DK-8000 Aarhus C, Denmark.


Elongation factor Tu (EF-Tu), the carrier of aa-tRNA to the mRNA-programmed ribosome, is the target of four families of antibiotics of unrelated structure, of which the action is supported by two basic mechanisms. Kirromycin and enacyloxin block EF-Tu.GDP on the ribosome; pulvomycin and GE2270 A inhibit the interaction of EF-Tu.GTP with aa-tRNA. The crystallographic analysis has unveiled the structural background of their actions, explaining how antibiotics of unrelated structures and binding modes and sites can employ similar mechanism of action. The selective similarities and differences of their binding sites and the induced EF-Tu conformations make understand how nature can affect the activities of a complex regulatory enzyme by means of low-molecular compounds, and have proposed a suitable approach for drug design.

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