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The mechanism of er...
The mechanism of error induction by the antibiotic viomycin provides insight into the fidelity mechanism of translation
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- Holm, Mikael, 1984- (författare)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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- Mandava, Chandra Sekhar, 1978- (författare)
- Uppsala universitet,Molekylärbiologi
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- Ehrenberg, Måns (författare)
- Uppsala universitet,Molekylärbiologi
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- Sanyal, Suparna (författare)
- Uppsala universitet,Molekylärbiologi
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(creator_code:org_t)
- ELIFE SCIENCES PUBLICATIONS LTD, 2019
- 2019
- Engelska.
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Ingår i: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 8
- Relaterad länk:
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https://doi.org/10.7...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.7...
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Abstract
Ämnesord
Stäng
- Applying pre-steady state kinetics to an Escherichia-coli-based reconstituted translation system, we have studied how the antibiotic viomycin affects the accuracy of genetic code reading. We find that viomycin binds to translating ribosomes associated with a ternary complex (TC) consisting of elongation factor Tu (EF-Tu), aminoacyl tRNA and GTP, and locks the otherwise dynamically flipping monitoring bases A1492 and A1493 into their active conformation. This effectively prevents dissociation of near- and non-cognate TCs from the ribosome, thereby enhancing errors in initial selection. Moreover, viomycin shuts down proofreading-based error correction. Our results imply a mechanism in which the accuracy of initial selection is achieved by larger backward rate constants toward TC dissociation rather than by a smaller rate constant for GTP hydrolysis for near- and non-cognate TCs. Additionally, our results demonstrate that translocation inhibition, rather than error induction, is the major cause of cell growth inhibition by viomycin.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
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- art (ämneskategori)
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