Differential Effects of Thiopeptide and Orthosomycin Antibiotics on Translational GTPases

Overview

Journal Chem Biol

Publisher Elsevier

Specialties Biochemistry
Biology
Chemistry

Date 2011 May 26

PMID 21609840

Citations 24

Authors

Aleksandra Mikolajka

Hanqing Liu

Yuanwei Chen

Agata L Starosta

Viter Marquez

Marina Ivanova

Barry S Cooperman

Daniel N Wilson

Affiliations

Soon will be listed here.

Abstract

The ribosome is a major target in the bacterial cell for antibiotics. Here, we dissect the effects that the thiopeptide antibiotics thiostrepton (ThS) and micrococcin (MiC) as well as the orthosomycin antibiotic evernimicin (Evn) have on translational GTPases. We demonstrate that, like ThS, MiC is a translocation inhibitor, and that the activation by MiC of the ribosome-dependent GTPase activity of EF-G is dependent on the presence of the ribosomal proteins L7/L12 as well as the G' subdomain of EF-G. In contrast, Evn does not inhibit translocation but is a potent inhibitor of back-translocation as well as IF2-dependent 70S-initiation complex formation. Collectively, these results shed insight not only into fundamental aspects of translation but also into the unappreciated specificities of these classes of translational inhibitors.

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