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Accuracy of genetic code translation and its orthogonal corruption by aminoglycosides and Mg(2+) ions
We studied the effects of aminoglycosides and changing Mg(2+) ion concentration on the accuracy of initial codon selection by aminoacyl-tRNA in ternary complex with elongation factor Tu and GTP (T(3)) on mRNA programmed ribosomes. Aminoglycosides decrease the accuracy by changing the equilibrium con...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814885/ https://www.ncbi.nlm.nih.gov/pubmed/29267976 http://dx.doi.org/10.1093/nar/gkx1256 |
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author | Zhang, Jingji Pavlov, Michael Y Ehrenberg, Måns |
author_facet | Zhang, Jingji Pavlov, Michael Y Ehrenberg, Måns |
author_sort | Zhang, Jingji |
collection | PubMed |
description | We studied the effects of aminoglycosides and changing Mg(2+) ion concentration on the accuracy of initial codon selection by aminoacyl-tRNA in ternary complex with elongation factor Tu and GTP (T(3)) on mRNA programmed ribosomes. Aminoglycosides decrease the accuracy by changing the equilibrium constants of ‘monitoring bases’ A1492, A1493 and G530 in 16S rRNA in favor of their ‘activated’ state by large, aminoglycoside-specific factors, which are the same for cognate and near-cognate codons. Increasing Mg(2+) concentration decreases the accuracy by slowing dissociation of T(3) from its initial codon- and aminoglycoside-independent binding state on the ribosome. The distinct accuracy-corrupting mechanisms for aminoglycosides and Mg(2+) ions prompted us to re-interpret previous biochemical experiments and functional implications of existing high resolution ribosome structures. We estimate the upper thermodynamic limit to the accuracy, the ‘intrinsic selectivity’ of the ribosome. We conclude that aminoglycosides do not alter the intrinsic selectivity but reduce the fraction of it that is expressed as the accuracy of initial selection. We suggest that induced fit increases the accuracy and speed of codon reading at unaltered intrinsic selectivity of the ribosome. |
format | Online Article Text |
id | pubmed-5814885 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-58148852018-02-23 Accuracy of genetic code translation and its orthogonal corruption by aminoglycosides and Mg(2+) ions Zhang, Jingji Pavlov, Michael Y Ehrenberg, Måns Nucleic Acids Res Nucleic Acid Enzymes We studied the effects of aminoglycosides and changing Mg(2+) ion concentration on the accuracy of initial codon selection by aminoacyl-tRNA in ternary complex with elongation factor Tu and GTP (T(3)) on mRNA programmed ribosomes. Aminoglycosides decrease the accuracy by changing the equilibrium constants of ‘monitoring bases’ A1492, A1493 and G530 in 16S rRNA in favor of their ‘activated’ state by large, aminoglycoside-specific factors, which are the same for cognate and near-cognate codons. Increasing Mg(2+) concentration decreases the accuracy by slowing dissociation of T(3) from its initial codon- and aminoglycoside-independent binding state on the ribosome. The distinct accuracy-corrupting mechanisms for aminoglycosides and Mg(2+) ions prompted us to re-interpret previous biochemical experiments and functional implications of existing high resolution ribosome structures. We estimate the upper thermodynamic limit to the accuracy, the ‘intrinsic selectivity’ of the ribosome. We conclude that aminoglycosides do not alter the intrinsic selectivity but reduce the fraction of it that is expressed as the accuracy of initial selection. We suggest that induced fit increases the accuracy and speed of codon reading at unaltered intrinsic selectivity of the ribosome. Oxford University Press 2018-02-16 2017-12-18 /pmc/articles/PMC5814885/ /pubmed/29267976 http://dx.doi.org/10.1093/nar/gkx1256 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Nucleic Acid Enzymes Zhang, Jingji Pavlov, Michael Y Ehrenberg, Måns Accuracy of genetic code translation and its orthogonal corruption by aminoglycosides and Mg(2+) ions |
title | Accuracy of genetic code translation and its orthogonal corruption by aminoglycosides and Mg(2+) ions |
title_full | Accuracy of genetic code translation and its orthogonal corruption by aminoglycosides and Mg(2+) ions |
title_fullStr | Accuracy of genetic code translation and its orthogonal corruption by aminoglycosides and Mg(2+) ions |
title_full_unstemmed | Accuracy of genetic code translation and its orthogonal corruption by aminoglycosides and Mg(2+) ions |
title_short | Accuracy of genetic code translation and its orthogonal corruption by aminoglycosides and Mg(2+) ions |
title_sort | accuracy of genetic code translation and its orthogonal corruption by aminoglycosides and mg(2+) ions |
topic | Nucleic Acid Enzymes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814885/ https://www.ncbi.nlm.nih.gov/pubmed/29267976 http://dx.doi.org/10.1093/nar/gkx1256 |
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