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<StructureSection load='7bt5' size='340' side='right'caption='[[7bt5]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
<StructureSection load='7bt5' size='340' side='right'caption='[[7bt5]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7bt5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum Plasmodium falciparum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BT5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BT5 FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BT5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BT5 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]] 2.493&#8491;</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]] 2.493&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F6O:N4-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-N2-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine'>F6O</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F6O:N4-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-N2-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine'>F6O</scene>, <scene name='pdbligand=LYS:LYSINE'>LYS</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=7bt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bt5 OCA], [https://pdbe.org/7bt5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bt5 RCSB], [https://www.ebi.ac.uk/pdbsum/7bt5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bt5 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=7bt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bt5 OCA], [https://pdbe.org/7bt5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bt5 RCSB], [https://www.ebi.ac.uk/pdbsum/7bt5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bt5 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q8IDJ8_PLAF7 Q8IDJ8_PLAF7]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Aminoacyl-tRNA synthetases are attractive targets for the development of antibacterial, antifungal, antiparasitic agents and for the treatment of other human diseases. Lysyl-tRNA synthetase (LysRS) from this family has been validated as a promising target for the development of antimalarial drugs. Here, we developed a high-throughput compatible assay and screened 1215 bioactive compounds to identify Plasmodium falciparum cytoplasmic LysRS (PfLysRS) inhibitor. ASP3026, an anaplastic lymphoma kinase inhibitor that was used in clinical trials for the treatment of B-cell lymphoma and solid tumors, was identified as a novel PfLysRS inhibitor. ASP3026 suppresses the enzymatic activity of PfLysRS at nanomolar potency, which is &gt;380-fold more effective than inhibition of the human counterpart. In addition, the compound suppressed blood-stage P. falciparum growth. To understand the molecular mechanism of inhibition by ASP3026, we further solved the cocrystal structure of PfLysRS-ASP3026 at a resolution of 2.49 A, providing clues for further optimization of the compound. Finally, primary structure-activity relationship analyses indicated that the inhibition of PfLysRS by ASP3026 is highly structure specific. This work not only provides a new chemical scaffold with good druggability for antimalarial development but also highlights the potential for repurposing kinase-inhibiting drugs to tRNA synthetase inhibitors to treat human diseases.
Inhibition of Plasmodium falciparum Lysyl-tRNA synthetase via an anaplastic lymphoma kinase inhibitor.,Zhou J, Huang Z, Zheng L, Hei Z, Wang Z, Yu B, Jiang L, Wang J, Fang P Nucleic Acids Res. 2020 Oct 14. pii: 5923426. doi: 10.1093/nar/gkaa862. PMID:33053158<ref>PMID:33053158</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7bt5" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
*[[Aminoacyl tRNA synthetase 3D structures|Aminoacyl tRNA synthetase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Plasmodium falciparum]]
[[Category: Fang P]]
[[Category: Fang P]]
[[Category: Wang J]]
[[Category: Wang J]]
[[Category: Zhou J]]
[[Category: Zhou J]]

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