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| - | | + | WITHDRAWN: The PDB entry 5UMB was withdrawn. |
| - | ==Crystal structure of ATPase domain of Malaria GRP78 with ADP bound==
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| - | <StructureSection load='5umb' size='340' side='right'caption='[[5umb]], [[Resolution|resolution]] 2.30Å' scene=''>
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| - | == Structural highlights ==
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| - | <table><tr><td colspan='2'>[[5umb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_NF54 Plasmodium falciparum NF54]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UMB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UMB FirstGlance]. <br>
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| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5umb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5umb OCA], [https://pdbe.org/5umb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5umb RCSB], [https://www.ebi.ac.uk/pdbsum/5umb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5umb ProSAT]</span></td></tr>
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| - | </table>
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| - | == Function ==
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| - | [[https://www.uniprot.org/uniprot/W7JXN5_PLAFO W7JXN5_PLAFO]]
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| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Drug resistant Plasmodium falciparum parasites represent a major obstacle in our efforts to control malaria, a deadly vector borne infectious disease. This situation creates an urgent need to find and validate new drug targets to contain the spread of the disease. Several genes associated with the unfolded protein response (UPR) including Glucose-regulated Protein 78 kDa (GRP78, also known as BiP) have been deemed potential drug targets. We explored the drug target potential of GRP78, a molecular chaperone that is a regulator of the UPR, for the treatment of P. falciparum parasite infection. By screening repurposed chaperone inhibitors that are anticancer agents, we showed that GRP78 inhibition is lethal to drug-sensitive and -resistant P. falciparum parasite strains in vitro. We correlated the antiplasmodial activity of the inhibitors with their ability to bind the malaria chaperone, by characterizing their binding to recombinant parasite GRP78. Furthermore, we determined the crystal structure of the ATP binding domain of P. falciparum GRP78 with ADP and identified structural features unique to the parasite. These data suggest that P. falciparum GRP78 can be a valid drug target and that its structural differences to human GRP78 emphasize potential to generate parasite specific compounds.
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| - | Repurposing drugs to target the malaria parasite unfolding protein response.,Chen Y, Murillo-Solano C, Kirkpatrick MG, Antoshchenko T, Park HW, Pizarro JC Sci Rep. 2018 Jul 9;8(1):10333. doi: 10.1038/s41598-018-28608-2. PMID:29985421<ref>PMID:29985421</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5umb" style="background-color:#fffaf0;"></div>
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| - | == References ==
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| - | <references/>
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| - | __TOC__
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| - | </StructureSection>
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| - | [[Category: Large Structures]]
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| - | [[Category: Plasmodium falciparum NF54]]
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| - | [[Category: Antoshchenko T]]
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| - | [[Category: Chen Y]]
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| - | [[Category: Park H]]
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| - | [[Category: Pizarro JC]]
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| - | [[Category: Song JH]]
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