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Open access
Nucleic Acids Research, volume 41, issue 14, pages e144

Identifying the targets of aminoacyl-tRNA synthetase inhibitors by primer extension inhibition

Orelle Cedric 1
Szal Teresa 2
Klepacki Dorota 2
Shaw Karen J 2
1
 
Center for Pharmaceutical Biotechnology, University of Illinois, Chicago, IL 60607, USA and Trius Therapeutics, Inc., San Diego, CA 92121, USA.
2
 
1Center for Pharmaceutical Biotechnology, University of Illinois, Chicago, IL 60607, USA and 2Trius Therapeutics, Inc., San Diego, CA 92121, USA
Publication typeJournal Article
Publication date2013-06-12
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor14.9
ISSN03051048, 13624962
PubMed ID:  23761439
Genetics
Abstract
Aminoacyl-transfer RNA (tRNA) synthetases (RS) are essential components of the cellular translation machinery and can be exploited for antibiotic discovery. Because cells have many different RS, usually one for each amino acid, identification of the specific enzyme targeted by a new natural or synthetic inhibitor can be cumbersome. We describe the use of the primer extension technique in conjunction with specifically designed synthetic genes to identify the RS targeted by an inhibitor. Suppression of a synthetase activity reduces the amount of the cognate aminoacyl-tRNA in a cell-free translation system resulting in arrest of translation when the corresponding codon enters the decoding center of the ribosome. The utility of the technique is demonstrated by identifying a switch in target specificity of some synthetic inhibitors of threonyl-tRNA synthetase.

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GOST |
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GOST Copy
Orelle C. et al. Identifying the targets of aminoacyl-tRNA synthetase inhibitors by primer extension inhibition // Nucleic Acids Research. 2013. Vol. 41. No. 14. p. e144.
GOST all authors (up to 50) Copy
Orelle C., Szal T., Klepacki D., Shaw K. J., Vázquez Laslop N., Mankin A. S. Identifying the targets of aminoacyl-tRNA synthetase inhibitors by primer extension inhibition // Nucleic Acids Research. 2013. Vol. 41. No. 14. p. e144.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1093/nar/gkt526
UR - https://doi.org/10.1093%2Fnar%2Fgkt526
TI - Identifying the targets of aminoacyl-tRNA synthetase inhibitors by primer extension inhibition
T2 - Nucleic Acids Research
AU - Orelle, Cedric
AU - Szal, Teresa
AU - Klepacki, Dorota
AU - Shaw, Karen J
AU - Vázquez Laslop, Nora
AU - Mankin, Alexander S.
PY - 2013
DA - 2013/06/12 00:00:00
PB - Oxford University Press
SP - e144
IS - 14
VL - 41
PMID - 23761439
SN - 0305-1048
SN - 1362-4962
ER -
BibTex |
Cite this
BibTex Copy
@article{2013_Orelle,
author = {Cedric Orelle and Teresa Szal and Dorota Klepacki and Karen J Shaw and Nora Vázquez Laslop and Alexander S. Mankin},
title = {Identifying the targets of aminoacyl-tRNA synthetase inhibitors by primer extension inhibition},
journal = {Nucleic Acids Research},
year = {2013},
volume = {41},
publisher = {Oxford University Press},
month = {jun},
url = {https://doi.org/10.1093%2Fnar%2Fgkt526},
number = {14},
pages = {e144},
doi = {10.1093/nar/gkt526}
}
MLA
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MLA Copy
Orelle, Cedric, et al. “Identifying the targets of aminoacyl-tRNA synthetase inhibitors by primer extension inhibition.” Nucleic Acids Research, vol. 41, no. 14, Jun. 2013, p. e144. https://doi.org/10.1093%2Fnar%2Fgkt526.
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