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Structural and functional characterization of the bacterial translocation inhibitor GE82832
Author(s) -
Brandi Letizia,
Maffioli Sonia,
Donadio Stefano,
Quaglia Fabio,
Sette Marco,
Milón Pohl,
Gualerzi Claudio O.,
Fabbretti Attilio
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.07.040
Subject(s) - ribosome , chromosomal translocation , ribosomal rna , chemistry , translation (biology) , protein subunit , transfer rna , ribosomal protein , protein biosynthesis , biochemistry , messenger rna , biology , biophysics , rna , gene
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.