View source for 2wfd


==Structure of the human cytosolic leucyl-tRNA synthetase editing domain==
<StructureSection load='2wfd' size='340' side='right'caption='[[2wfd]], [[Resolution|resolution]] 3.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2wfd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WFD 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]] 3.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=2wfd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wfd OCA], [https://pdbe.org/2wfd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wfd RCSB], [https://www.ebi.ac.uk/pdbsum/2wfd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wfd ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SYLC_HUMAN SYLC_HUMAN] Acute infantile liver failure-multisystemic involvement syndrome. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/SYLC_HUMAN SYLC_HUMAN] Catalyzes the specific attachment of an amino acid to its cognate tRNA in a two step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA. Exhibits a post-transfer editing activity to hydrolyze mischarged tRNAs.<ref>PMID:19426743</ref> 
== 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/wf/2wfd_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2wfd ConSurf].
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== 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<ref>PMID:19426743</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2wfd" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Alley MRK]]
[[Category: Baker SJ]]
[[Category: Cusack S]]
[[Category: Hernandez V]]
[[Category: Mao W]]
[[Category: Plattner JJ]]
[[Category: Seiradake E]]