Title
Structural and functional characterization of the bacterial translocation inhibitor GE82832
Date Issued
21 September 2012
Access level
open access
Resource Type
journal article
Author(s)
Brandi L.
Maffioli S.
Donadio S.
Quaglia F.
Sette M.
Gualerzi C.O.
Fabbretti A.
University of Camerino
Abstract
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. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Start page
3373
End page
3378
Volume
586
Issue
19
Language
English
OCDE Knowledge area
Biología celular, Microbiología
Subjects
Scopus EID
2-s2.0-84866625243
PubMed ID
Source
FEBS Letters
ISSN of the container
18733468
Sponsor(s)
We are grateful to Professor S. Omura (Tokyo) for providing a sample of dityromycin and to Professor Cynthia L. Pon (Camerino) for her invaluable discussions and suggestions in the preparation of this manuscript. This work was started with the financial support of the EC Grant (Contract QLRT-2001-00892 “Ribosome inhibitors”) to C.O.G. and L.B. and later partially supported by a Grant from Regione Lombardia (Bando ATP). We also acknowledge the early contribution of former colleagues at Biosearch Italia, spa (Gerenzano).
Sources of information:
Directorio de Producción Científica
Scopus