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Elongation factor Tu (EF-Tu) is a highly conserved and essential bacterial GTPase that plays a central role in protein biosynthesis [UniProt: Q18C08]. It is responsible for transporting aminoacyl-tRNA to the A-site of the ribosome in a GTP-dependent manner. Upon correct codon-anticodon recognition, GTP is hydrolyzed to GDP, and the resulting EF-Tu•GDP complex is released from the ribosome to be recycled by the guanine nucleotide exchange factor EF-Ts. In Clostridioides difficile, EF-Tu has emerged as a significant therapeutic target, particularly for the development of narrow-spectrum antibiotics like LFF571 [PubMed: 23114770]. By inhibiting EF-Tu, these drugs halt bacterial translation, leading to cell death or growth inhibition. Because EF-Tu is distinct from its eukaryotic homolog (eEF-1A), it offers a high degree of selectivity for bacterial pathogens over human cells [Wikipedia: EF-Tu].
Inhibition of bacterial protein synthesis by binding to EF-Tu and preventing either the formation of the ternary complex with aminoacyl-tRNA or the release of EF-Tu from the ribosome after GTP hydrolysis [PubMed: 23114770].
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