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<StructureSection load='6lpf' size='340' side='right'caption='[[6lpf]], [[Resolution|resolution]] 2.49Å' scene=''> | <StructureSection load='6lpf' size='340' side='right'caption='[[6lpf]], [[Resolution|resolution]] 2.49Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6lpf]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LPF OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6lpf]] 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=6LPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LPF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LSS:5-O-(L-LEUCYLSULFAMOYL)ADENOSINE'>LSS</scene>, <scene name='pdbligand=VRT:2-(L-NORVALYL)AMINO-2-DEOXYADENOSINE'>VRT</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.49Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LSS:5-O-(L-LEUCYLSULFAMOYL)ADENOSINE'>LSS</scene>, <scene name='pdbligand=VRT:2-(L-NORVALYL)AMINO-2-DEOXYADENOSINE'>VRT</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6lpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lpf OCA], [https://pdbe.org/6lpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lpf RCSB], [https://www.ebi.ac.uk/pdbsum/6lpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lpf ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == 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 == | == 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6lpf" 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: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Cusack S]] | |||
[[Category: Cusack | [[Category: Li H]] | ||
[[Category: Li | [[Category: Li J]] | ||
[[Category: Li | [[Category: Lin JZ]] | ||
[[Category: Lin | [[Category: Liu RJ]] | ||
[[Category: Liu | [[Category: Long T]] | ||
[[Category: Long | [[Category: Palencia A]] | ||
[[Category: Palencia | [[Category: Wang ED]] | ||
[[Category: Wang | [[Category: Wang MZ]] | ||
[[Category: Wang | [[Category: Zhao JH]] | ||
[[Category: Zhao | |||
Latest revision as of 17:42, 29 November 2023
The crystal structure of human cytoplasmic LRSThe crystal structure of human cytoplasmic LRS
Structural highlights
DiseaseSYLC_HUMAN Acute infantile liver failure-multisystemic involvement syndrome. The disease is caused by mutations affecting the gene represented in this entry. FunctionSYLC_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 PubMedHuman 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 AlsoReferences
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