2v0g: Difference between revisions
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==Overview== | ==Overview== | ||
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 .. | 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. | ||
==About this Structure== | ==About this Structure== | ||
2V0G is a | 2V0G is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus] with ZN, HG, SO4 and LEU as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2V0G OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: synthetase]] | [[Category: synthetase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:47:15 2007'' | ||
