Fusidic acid targets elongation factor G in several stages of translocation on the bacterial ribosome
(2015) In Journal of Biological Chemistry 290(6). p.3440-3454- Abstract
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... (More)
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 (K50% ≈ 1 μM), discuss the identity of the FA targeted states, and place existing cryo-EM and crystal structures in their functional context.
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- author
- Borg, Anneli
; Holm, Mikael
; Shiroyama, Ikue
; Hauryliuk, Vasili
LU
; Pavlov, Michael ; Sanyal, Suparna LU and Ehrenberg, Måns
- publishing date
- 2015-02-06
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 290
- issue
- 6
- pages
- 15 pages
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:25451927
- scopus:84922373723
- ISSN
- 0021-9258
- DOI
- 10.1074/jbc.M114.611608
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Copyright: Copyright 2015 Elsevier B.V., All rights reserved.
- id
- e6236a11-1185-4f9e-b44e-6fa8a8f4a10a
- date added to LUP
- 2021-09-24 20:43:30
- date last changed
- 2024-04-06 08:45:35
@article{e6236a11-1185-4f9e-b44e-6fa8a8f4a10a, abstract = {{<p>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<sub>50%</sub> ≈ 1 μM), discuss the identity of the FA targeted states, and place existing cryo-EM and crystal structures in their functional context.</p>}}, author = {{Borg, Anneli and Holm, Mikael and Shiroyama, Ikue and Hauryliuk, Vasili and Pavlov, Michael and Sanyal, Suparna and Ehrenberg, Måns}}, issn = {{0021-9258}}, language = {{eng}}, month = {{02}}, number = {{6}}, pages = {{3440--3454}}, publisher = {{American Society for Biochemistry and Molecular Biology}}, series = {{Journal of Biological Chemistry}}, title = {{Fusidic acid targets elongation factor G in several stages of translocation on the bacterial ribosome}}, url = {{http://dx.doi.org/10.1074/jbc.M114.611608}}, doi = {{10.1074/jbc.M114.611608}}, volume = {{290}}, year = {{2015}}, }