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== | ==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.== | ||
Aminoacyl-transfer RNA (tRNA) synthetases, which catalyze the attachment | <StructureSection load='2v0g' size='340' side='right'caption='[[2v0g]], [[Resolution|resolution]] 3.50Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2v0g]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V0G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V0G FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANZ:[(6-AMINO-9H-PURIN-9-YL)-[5-FLUORO-1,3-DIHYDRO-1-HYDROXY-2,1-BENZOXABOROLE]-4YL]METHYL+DIHYDROGEN+PHOSPHATE'>ANZ</scene>, <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>, <scene name='pdbligand=LEU:LEUCINE'>LEU</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2v0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v0g OCA], [https://pdbe.org/2v0g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v0g RCSB], [https://www.ebi.ac.uk/pdbsum/2v0g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v0g ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q7SIE4_THETH Q7SIE4_THETH] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v0/2v0g_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2v0g ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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<ref>PMID:17588934</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
[[Category: | <div class="pdbe-citations 2v0g" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] | |||
*[[Transfer RNA (tRNA)|Transfer RNA (tRNA)]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Thermus thermophilus]] | [[Category: Thermus thermophilus]] | ||
[[Category: Akama | [[Category: Akama T]] | ||
[[Category: Alley | [[Category: Alley MRK]] | ||
[[Category: Baker | [[Category: Baker S]] | ||
[[Category: Benkovic | [[Category: Benkovic SJ]] | ||
[[Category: Crepin | [[Category: Crepin T]] | ||
[[Category: Cusack | [[Category: Cusack S]] | ||
[[Category: Hernandez | [[Category: Hernandez V]] | ||
[[Category: Mao | [[Category: Mao W]] | ||
[[Category: Martinis | [[Category: Martinis SA]] | ||
[[Category: Plattner | [[Category: Plattner J]] | ||
[[Category: Rock | [[Category: Rock F]] | ||
[[Category: Shapiro | [[Category: Shapiro L]] | ||
[[Category: Tukalo | [[Category: Tukalo M]] | ||
[[Category: Yaremchuk | [[Category: Yaremchuk A]] | ||
[[Category: Zhang | [[Category: Zhang Y]] | ||
[[Category: Zhou | [[Category: Zhou H]] | ||
Latest revision as of 18:00, 13 December 2023
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.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.
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAminoacyl-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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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