Fusidic Acid Targets Elongation Factor G in Several Stages of Translocation on the Bacterial Ribosome
2015 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 290, no 6, 3440-3454 p.Article in journal (Refereed) Published
The antibiotic fusidic acid (FA) targets elongation factor G (EF-G) and inhibits ribosomal peptide elongation and ribosome recycling, but deeper mechanistic aspects of FA action have remained unknown. Using quench flow and stopped flow experiments in a biochemical system for protein synthesis and taking advantage of separate time scales for inhibited (10 s) and uninhibited (100 ms) elongation cycles, a detailed kinetic model of FA action was obtained. FA targets EF-G at an early stage in the translocation process (I), which proceeds unhindered by the presence of the drug to a later stage (II), where the ribosome stalls. Stalling may also occur at a third stage of translocation(III), just before release of EF-G from the post-translocation ribosome. We show that FA is a strong elongation inhibitor (K-50% approximate to 1 mu M), discuss the identity of the FA targeted states, and place existing cryo-EM and crystal structures in their functional context.
Place, publisher, year, edition, pages
2015. Vol. 290, no 6, 3440-3454 p.
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-247496DOI: 10.1074/jbc.M114.611608ISI: 000349456000020PubMedID: 25451927OAI: oai:DiVA.org:uu-247496DiVA: diva2:796429