Structural basis for potent inhibitory activity of the antibiotic tigecycline during protein synthesis

作者：L. Jenner, Agata L. Starosta, Daniel S. Terry, Aleksandra Mikolajka, Liudmila Filonava, Marat Yusupov, Scott C. Blanchard, Daniel N. Wilson, G. Yusupova · 发表于：Proceedings of the National Academy of Sciences · 年份：2013 · DOI：10.1073/pnas.1216691110 · 被引用次数：201 · 研究领域：Antibiotic Resistance in Bacteria、Advanced biosensing and bioanalysis techniques、Bacteriophages and microbial interactions

Here we present an X-ray crystallography structure of the clinically relevant tigecycline antibiotic bound to the 70S ribosome. Our structural and biochemical analysis indicate that the enhanced potency of tigecycline results from a stacking interaction with nucleobase C1054 within the decoding site of the ribosome. Single-molecule fluorescence resonance energy transfer studies reveal that, during decoding, tigecycline inhibits the initial codon recognition step of tRNA accommodation and prevents rescue by the tetracycline-resistance protein TetM.