View source for 6lr6


==The crystal structure of human cytoplasmic LRS==
<StructureSection load='6lr6' size='340' side='right'caption='[[6lr6]], [[Resolution|resolution]] 3.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6lr6]] 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=6LR6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LR6 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]] 3.009&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A2H:4-CHLORO-3-AMINOMETHYL-7-[ETHOXY]-3H-BENZO[C][1,2]OXABOROL-1-OL+MODIFIED+ADENOSINE'>A2H</scene>, <scene name='pdbligand=LSS:5-O-(L-LEUCYLSULFAMOYL)ADENOSINE'>LSS</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=6lr6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lr6 OCA], [https://pdbe.org/6lr6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lr6 RCSB], [https://www.ebi.ac.uk/pdbsum/6lr6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lr6 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human cytosolic leucyl-tRNA synthetase (hcLRS) is an essential and multifunctional enzyme. Its canonical function is to catalyze the covalent ligation of leucine to tRNALeu, and it may also hydrolyze mischarged tRNAs through an editing mechanism. Together with eight other aminoacyl-tRNA synthetases (AaRSs) and three auxiliary proteins, it forms a large multi-synthetase complex (MSC). Beyond its role in translation, hcLRS has an important moonlight function as a leucine sensor in the rapamycin complex 1 (mTORC1) pathway. Since this pathway is active in cancer development, hcLRS is a potential target for anti-tumor drug development. Moreover, LRS from pathogenic microbes are proven drug targets for developing antibiotics, which however should not inhibit hcLRS. Here we present the crystal structure of hcLRS at a 2.5 A resolution, the first complete structure of a eukaryotic LRS, and analyze the binding of various compounds that target different sites of hcLRS. We also deduce the assembly mechanism of hcLRS into the MSC through reconstitution of the entire mega complex in vitro. Overall, our study provides the molecular basis for understanding both the multifaceted functions of hcLRS and for drug development targeting these functions.

Molecular basis of the multifaceted functions of human leucyl-tRNA synthetase in protein synthesis and beyond.,Liu RJ, Long T, Li H, Zhao J, Li J, Wang M, Palencia A, Lin J, Cusack S, Wang ED Nucleic Acids Res. 2020 Mar 30. pii: 5813801. doi: 10.1093/nar/gkaa189. PMID:32232361<ref>PMID:32232361</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6lr6" 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: Cusack S]]
[[Category: Li H]]
[[Category: Li J]]
[[Category: Lin JZ]]
[[Category: Liu RJ]]
[[Category: Long T]]
[[Category: Palencia A]]
[[Category: Wang ED]]
[[Category: Wang MZ]]
[[Category: Zhao JH]]