2V0G
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.
Summary for 2V0G
| Entry DOI | 10.2210/pdb2v0g/pdb |
| Related | 1H3N 1OBC 1OBH 2BTE 2BYT 2V0C |
| Descriptor | AMINOACYL-TRNA SYNTHETASE, TRNALEU, LEUCINE, ... (6 entities in total) |
| Functional Keywords | class i aminoacyl- trna synthetase, protein biosynthesis, aminoacyl-trna synthetase, atp + l-leucine + trna (leu) gives amp + ppi l-leucyl-trna synthetase, metal-binding, nucleotide-binding zinc, ligase, editing, synthetase, atp-binding |
| Biological source | THERMUS THERMOPHILUS More |
| Total number of polymer chains | 4 |
| Total formula weight | 258287.99 |
| Authors | Rock, F.,Mao, W.,Yaremchuk, A.,Tukalo, M.,Crepin, T.,Zhou, H.,Zhang, Y.,Hernandez, V.,Akama, T.,Baker, S.,Plattner, J.,Shapiro, L.,Martinis, S.A.,Benkovic, S.J.,Cusack, S.,Alley, M.R.K. (deposition date: 2007-05-14, release date: 2007-07-03, Last modification date: 2023-12-13) |
| Primary citation | Rock, F.,Mao, W.,Yaremchuk, A.,Tukalo, M.,Crepin, T.,Zhou, H.,Zhang, Y.,Hernandez, V.,Akama, T.,Baker, S.,Plattner, J.,Shapiro, L.,Martinis, S.A.,Benkovic, S.J.,Cusack, S.,Alley, M.R.K. An Antifungal Agent Inhibits an Aminoacyl-tRNA Synthetase by Trapping tRNA in the Editing Site. Science, 316:1759-, 2007 Cited by PubMed Abstract: 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. PubMed: 17588934DOI: 10.1126/SCIENCE.1142189 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.5 Å) |
Structure validation
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