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| | ==Structure of the Candida albicans cytosolic leucyl-tRNA synthetase editing domain== | | ==Structure of the Candida albicans cytosolic leucyl-tRNA synthetase editing domain== |
| - | <StructureSection load='2wfe' size='340' side='right' caption='[[2wfe]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='2wfe' size='340' side='right'caption='[[2wfe]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2wfe]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_11006_[[candida_stellatoidea]] Atcc 11006 [[candida stellatoidea]]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WFE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WFE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2wfe]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_albicans Candida albicans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WFE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WFE FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wfg|2wfg]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2wfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wfe OCA], [http://pdbe.org/2wfe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wfe RCSB], [http://www.ebi.ac.uk/pdbsum/2wfe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wfe ProSAT]</span></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=2wfe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wfe OCA], [https://pdbe.org/2wfe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wfe RCSB], [https://www.ebi.ac.uk/pdbsum/2wfe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wfe ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
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| | ==See Also== | | ==See Also== |
| - | *[[Aminoacyl tRNA Synthetase|Aminoacyl tRNA Synthetase]] | + | *[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]] |
| - | *[[Leucyl-tRNA Synthetase|Leucyl-tRNA Synthetase]]
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Alley, M R.K]] | + | [[Category: Candida albicans]] |
| - | [[Category: Baker, S J]] | + | [[Category: Large Structures]] |
| - | [[Category: Cusack, S]] | + | [[Category: Alley MRK]] |
| - | [[Category: Hernandez, V]] | + | [[Category: Baker SJ]] |
| - | [[Category: Mao, W]] | + | [[Category: Cusack S]] |
| - | [[Category: Plattner, J J]] | + | [[Category: Hernandez V]] |
| - | [[Category: Seiradake, E]] | + | [[Category: Mao W]] |
| - | [[Category: Candida albican]] | + | [[Category: Plattner JJ]] |
| - | [[Category: Editing domain]] | + | [[Category: Seiradake E]] |
| - | [[Category: Hydrolysis of mis-charged trna]]
| + | |
| - | [[Category: Leucyl-trna synthetase]]
| + | |
| - | [[Category: Ligase]]
| + | |
| Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Leucyl-tRNA synthetase (LeuRS) specifically links leucine to the 3' end of tRNA(leu) isoacceptors. The overall accuracy of the two-step aminoacylation reaction is enhanced by an editing domain that hydrolyzes mischarged tRNAs, notably ile-tRNA(leu). We present crystal structures of the editing domain from two eukaryotic cytosolic LeuRS: human and fungal pathogen Candida albicans. In comparison with previous structures of the editing domain from bacterial and archeal kingdoms, these structures show that the LeuRS editing domain has a conserved structural core containing the active site for hydrolysis, with distinct bacterial, archeal, or eukaryotic specific peripheral insertions. It was recently shown that the benzoxaborole antifungal compound AN2690 (5-fluoro-1,3-dihydro-1-hydroxy-1,2-benzoxaborole) inhibits LeuRS by forming a covalent adduct with the 3' adenosine of tRNA(leu) at the editing site, thus locking the enzyme in an inactive conformation. To provide a structural basis for enhancing the specificity of these benzoxaborole antifungals, we determined the structure at 2.2 A resolution of the C. albicans editing domain in complex with a related compound, AN3018 (6-(ethylamino)-5-fluorobenzo[c][1,2]oxaborol-1(3H)-ol), using AMP as a surrogate for the 3' adenosine of tRNA(leu). The interactions between the AN3018-AMP adduct and C. albicans LeuRS are similar to those previously observed for bacterial LeuRS with the AN2690 adduct, with an additional hydrogen bond to the extra ethylamine group. However, compared to bacteria, eukaryotic cytosolic LeuRS editing domains contain an extra helix that closes over the active site, largely burying the adduct and providing additional direct and water-mediated contacts. Small differences between the human domain and the fungal domain could be exploited to enhance fungal specificity.
Crystal structures of the human and fungal cytosolic Leucyl-tRNA synthetase editing domains: A structural basis for the rational design of antifungal benzoxaboroles.,Seiradake E, Mao W, Hernandez V, Baker SJ, Plattner JJ, Alley MR, Cusack S J Mol Biol. 2009 Jul 10;390(2):196-207. Epub 2009 May 6. PMID:19426743[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Seiradake E, Mao W, Hernandez V, Baker SJ, Plattner JJ, Alley MR, Cusack S. Crystal structures of the human and fungal cytosolic Leucyl-tRNA synthetase editing domains: A structural basis for the rational design of antifungal benzoxaboroles. J Mol Biol. 2009 Jul 10;390(2):196-207. Epub 2009 May 6. PMID:19426743 doi:10.1016/j.jmb.2009.04.073
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