2v0c
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| , resolution 1.85Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , , , , , , , , and | ||||||
| Ligands: | , , , , | ||||||
| Domains: | Anticodon_1, leuS, LeuRS_core | ||||||
| Related: | 1H3N, 1OBC, 1OBH, 2BTE, 2BYT
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
LEUCYL-TRNA SYNTHETASE FROM THERMUS THERMOPHILUS COMPLEXED WITH A SULPHAMOYL ANALOGUE OF LEUCYL-ADENYLATE IN THE SYNTHETIC SITE AND AN ADDUCT OF AMP WITH 5-FLUORO-1,3-DIHYDRO-1-HYDROXY-2,1-BENZOXABOROLE (AN2690) IN THE EDITING SITE
OverviewOverview
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 StructureAbout this Structure
2V0C is a Single protein structure of sequence from Thermus thermophilus. Full crystallographic information is available from OCA.
ReferenceReference
An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site., Rock FL, Mao W, Yaremchuk A, Tukalo M, Crepin T, Zhou H, Zhang YK, Hernandez V, Akama T, Baker SJ, Plattner JJ, Shapiro L, Martinis SA, Benkovic SJ, Cusack S, Alley MR, Science. 2007 Jun 22;316(5832):1759-61. PMID:17588934
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- Single protein
- Thermus thermophilus
- Akama, T.
- Alley, M R.K.
- Baker, S.
- Benkovic, S J.
- Crepin, T.
- Cusack, S.
- Hernandez, V.
- Mao, W.
- Martinis, S A.
- Plattner, J.
- Rock, F.
- Shapiro, L.
- Tukalo, M.
- Yaremchuk, A.
- Zhang, Y.
- Zhou, H.
- Aminoacyl-trna synthetase
- Atp + l-leucine + trna (leu) gives amp + ppi + l-leucyl-trna(leu)
- Atp-binding
- Clss i aminoacyl-trna synthetase
- Ligase
- Metal-binding
- Nucleotide-binding
- Protein biosynthesis
- Zinc