2v0g: Difference between revisions
No edit summary |
No edit summary |
||
| Line 5: | Line 5: | ||
==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== | ||
| Line 45: | Line 45: | ||
[[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'' | ||
Revision as of 15:41, 5 November 2007
|
LEUCYL-TRNA SYNTHETASE FROM THERMUS THERMOPHILUS COMPLEXED WITH A TRNA(LEU) TRANSCRIPT WITH 5-FLUORO-1,3-DIHYDRO-1-HYDROXY-2,1-BENZOXABOROLE (AN2690) FORMING AN ADDUCT TO THE RIBOSE OF ADENOSINE-76 IN THE ENZYME 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
2V0G is a Protein complex structure of sequences from Thermus thermophilus with ZN, HG, SO4 and LEU as ligands. Structure known Active Site: AC1. 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
Page seeded by OCA on Mon Nov 5 14:47:15 2007
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Protein complex
- 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.
- HG
- LEU
- SO4
- ZN
- Aminoacyl-trna synthetase
- Atp + l-leucine + trna (leu) gives amp + ppi l-leucyl-trna synthetase
- Atp- binding
- Class i aminoacyl- trna synthetase
- Editing
- Ligase
- Metal-binding
- Nucleotide-binding zinc
- Protein biosynthesis
- Synthetase