The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
An Antifungal Agent Inhibits an Aminoacyl-tRNA Synthetase by Trapping tRNA in the Editing Site
Open accessAbstract
Aminoacyl–transfer RNA (tRNA) synthetases, which catalyze the attachment of the correct amino acid to its corresponding tRNA during translation of the genetic code, are proven antimicrobial drug targets. We show that the broad-spectrum antifungal 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690), in development for the treatment of onychomycosis, inhibits yeast cytoplasmic leucyl-tRNA synthetase by formation of a stable tRNA Leu -AN2690 adduct in the editing site of the enzyme. Adduct formation is mediated through the boron atom of AN2690 and the 2′- and 3′-oxygen atoms of tRNA's3′-terminal adenosine. The trapping of enzyme-bound tRNA Leu in the editing site prevents catalytic turnover, thus inhibiting synthesis of leucyl-tRNA Leu and consequentially blocking protein synthesis. This result establishes the editing site as a bona fide target for aminoacyl-tRNA synthetase inhibitors.
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Cites
Ibba, M., & Söll, D. (2000) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.69.1.617 · Cited by 1,459
Dowlut, M., & Hall, D. G. (2006) · Journal of the American Chemical Society · doi:10.1021/ja057798c · Cited by 434
Baker, S. J., Zhang, Y.-K., Akama, T., Lau, A., Zhou, H., Hernandez, V., Mao, W., Alley, M. R. K., Sanders, V., & Plattner, J. J. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm0603724 · Cited by 314
Self-citationThe 2 Å crystal structure of leucyl-tRNA synthetase and its complex with a leucyl-adenylate analogue
Cusack, S., Yaremchuk, A., & Tukalo, M. (2000) · The EMBO Journal · doi:10.1093/emboj/19.10.2351 · Cited by 259
Self-citationStructural and Mechanistic Basis of Pre- and Posttransfer Editing by Leucyl-tRNA Synthetase
Lincecum, T. L., Tukalo, M., Yaremchuk, A., Mursinna, R. S., Williams, A. M., Sproat, B. S., Van Den Eynde, W., Link, A., Van Calenbergh, S., Grøtli, M., et al. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00098-4 · Cited by 217
Self-citationTukalo, M. A., Yaremchuk, A. D., Fukunaga, R., Yokoyama, S., & Cusack, S. (2005) · Nature Structural & Molecular Biology · doi:10.1038/nsmb986 · Cited by 155
Self-citationMursinna, R. S., Lincecum, T. L., & Martinis, S. A. (2001) · Biochemistry · doi:10.1021/bi002915w · Cited by 108
Self-citationFukunaga, R., & Yokoyama, S. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.11.060 · Cited by 100
Ricardo, A., Frye, F., Carrigan, M. A., Tipton, J. D., Powell, D. H., & Benner, S. A. (2006) · The Journal of Organic Chemistry · doi:10.1021/jo061770h · Cited by 62
Making connections: RNA-dependent amino acid recognition
SCHIMMEL, P. R., & Schmidt, E. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)88937-9 · Cited by 30
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Boike, L., Henning, N. J., & Nomura, D. K. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00542-z · Cited by 823
Antifungal Drug Development: Challenges, Unmet Clinical Needs, and New Approaches
Roemer, T., & Krysan, D. J. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019703 · Cited by 593
Campoy, S., & Adrio, J. L. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2016.11.019 · Cited by 511
Therapeutic Potential of Boron-Containing Compounds
Baker, S. J., Ding, C. Z., Akama, T., Zhang, Y.-K., Hernandez, V., & Xia, Y. (2009) · Future Medicinal Chemistry · doi:10.4155/fmc.09.71 · Cited by 373
Self-citationNew agents for the treatment of drug-resistant Mycobacterium tuberculosis
Hoagland, D. T., Liu, J., Lee, R. B., & Lee, R. E. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.04.026 · Cited by 328
Metadata
- Authors
- Rock, F. L., Mao, W., Yaremchuk, A., Tukalo, M., Crépin, T., Zhou, H., Zhang, Y.-K., Hernandez, V., Akama, T., Baker, S. J., Plattner, J. J., Shapiro, L., Martinis, S. A., Benkovic, S. J., Cusack, S., & Alley, M. R. K.
- Venue
- Science
- Published
- 2007-06-22
- Volume
- 316
- Issue
- 5832
- Pages
- 1759-1761
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2009746802
- Cited by
- 631
- References
- 10
- FWCI
- 7.66
- Type
- journal article
- Language
- en
- Open access
- green
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- Rock, F. L., Mao, W., Yaremchuk, A., Tukalo, M., Crépin, T., Zhou, H., Zhang, Y.-K., Hernandez, V., Akama, T., Baker, S. J., Plattner, J. J., Shapiro, L., Martinis, S. A., Benkovic, S. J., Cusack, S., & Alley, M. R. K. (2007). An Antifungal Agent Inhibits an Aminoacyl-tRNA Synthetase by Trapping tRNA in the Editing Site. Science. https://doi.org/10.1126/science.1142189
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