Structural and functional characterization of the bacterial translocation inhibitor GE82832

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• 作者：Letizia Br ; i ; Sonia Maffioli ; Stefano Donadio ; Fabio Quaglia ; Marco Sette ; Pohl Mil¨®n ; Claudio O. Gualerzi ; Attilio Fabbretti
• 关键词：Dityromycin ; Translation ; Translocation inhibitor ; Natural product ; Ribosome
• 刊名：FEBS Letters
• 出版年：2012
• 出版时间：21 September, 2012
• 年：2012
• 卷：586
• 期：19
• 页码：3373-3378
• 全文大小：952 K

文摘

The structure of GE82832, a translocation inhibitor produced by a soil microorganism, is shown to be highly related to that of dityromycin, a bicyclodecadepsipeptide antibiotic discovered long ago whose characterization had never been pursued beyond its structural elucidation. GE82832 and dityromycin were shown to interfere with both aminoacyl-tRNA and mRNA movement and with the Pi release occurring after ribosome- and EF-G-dependent GTP hydrolysis. These findings and the unusual ribosomal localization of GE82832/dityromycin near protein S13 suggest that the mechanism of inhibition entails an interference with the rotation of the 30S subunit ¡°head¡± which accompanies the ribosome-unlocking step of translocation.