Structural basis for potent inhibitory activity of the antibiotic tigecycline during protein synthesis
Structural basis for potent inhibitory activity of the antibiotic tigecycline during protein synthesis
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DOI：
10.1073/pnas.1216691110
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发表时间：
2013-03-05
影响因子：
11.1
通讯作者：
Yusupova, Gulnara
中科院分区：
文献类型：
--
作者：
Jenner, Lasse;Starosta, Agata L.;Yusupova, Gulnara
在这里，我们提出了与70年代核糖体结合的临床相关替格环素抗生素的X射线结晶学结构。我们的结构和生化分析表明，替吉环素的增强效力是由于在核糖体的解码位置与核苷酸碱基C1054的堆积相互作用所致。单分子荧光共振能量转移研究表明，在解码过程中，替格环素抑制tRNA调节的初始密码子识别步骤，并阻止四环素耐药蛋白TetM的拯救。
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.