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| | <StructureSection load='6lr6' size='340' side='right'caption='[[6lr6]], [[Resolution|resolution]] 3.01Å' scene=''> | | <StructureSection load='6lr6' size='340' side='right'caption='[[6lr6]], [[Resolution|resolution]] 3.01Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6lr6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://proteopedia.org/fgij/fg.htm?mol=6LR6 FirstGlance]. <br> | + | <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='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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.009Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LARS, KIAA1352 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Leucine--tRNA_ligase Leucine--tRNA ligase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=6.1.1.4 6.1.1.4] </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=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> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6lr6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lr6 OCA], [http://pdbe.org/6lr6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6lr6 RCSB], [http://www.ebi.ac.uk/pdbsum/6lr6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6lr6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://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. | + | [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 == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6lr6" style="background-color:#fffaf0;"></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 == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Leucine--tRNA ligase]]
| + | [[Category: Cusack S]] |
| - | [[Category: Cusack, S]] | + | [[Category: Li H]] |
| - | [[Category: Li, H]] | + | [[Category: Li J]] |
| - | [[Category: Li, J]] | + | [[Category: Lin JZ]] |
| - | [[Category: Lin, J Z]] | + | [[Category: Liu RJ]] |
| - | [[Category: Liu, R J]] | + | [[Category: Long T]] |
| - | [[Category: Long, T]] | + | [[Category: Palencia A]] |
| - | [[Category: Palencia, A]] | + | [[Category: Wang ED]] |
| - | [[Category: Wang, E D]] | + | [[Category: Wang MZ]] |
| - | [[Category: Wang, M Z]] | + | [[Category: Zhao JH]] |
| - | [[Category: Zhao, J H]] | + | |
| - | [[Category: Aminoacylation]]
| + | |
| - | [[Category: Leur]]
| + | |
| - | [[Category: Protein translation]]
| + | |
| - | [[Category: Rna binding protein]]
| + | |
| - | [[Category: Trna]]
| + | |
| Structural highlights
Disease
SYLC_HUMAN Acute infantile liver failure-multisystemic involvement syndrome. The disease is caused by mutations affecting the gene represented in this entry.
Function
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.[1]
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[2]
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
- ↑ Liu RJ, Long T, Li H, Zhao J, Li J, Wang M, Palencia A, Lin J, Cusack S, Wang ED. Molecular basis of the multifaceted functions of human leucyl-tRNA synthetase in protein synthesis and beyond. Nucleic Acids Res. 2020 Mar 30. pii: 5813801. doi: 10.1093/nar/gkaa189. PMID:32232361 doi:http://dx.doi.org/10.1093/nar/gkaa189
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