7udq

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'''Unreleased structure'''
 
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The entry 7udq is ON HOLD until Paper Publication
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==Crystal structure of COQ8A-CA157 inhibitor complex in space group P1==
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<StructureSection load='7udq' size='340' side='right'caption='[[7udq]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7udq]] 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=7UDQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UDQ 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=MVS:4-[(3,4,5-trimethoxyphenyl)amino]quinoline-7-carbonitrile'>MVS</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=7udq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7udq OCA], [https://pdbe.org/7udq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7udq RCSB], [https://www.ebi.ac.uk/pdbsum/7udq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7udq ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/COQ8A_HUMAN COQ8A_HUMAN] Autosomal recessive ataxia due to ubiquinone deficiency. The disease is caused by variants affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/COQ8A_HUMAN COQ8A_HUMAN] Atypical kinase involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration (PubMed:25498144, PubMed:21296186, PubMed:25540914, PubMed:27499294). Its substrate specificity is unclear: does not show any protein kinase activity (PubMed:25498144, PubMed:27499294). Probably acts as a small molecule kinase, possibly a lipid kinase that phosphorylates a prenyl lipid in the ubiquinone biosynthesis pathway, as suggested by its ability to bind coenzyme Q lipid intermediates (PubMed:25498144, PubMed:27499294). Shows an unusual selectivity for binding ADP over ATP (PubMed:25498144).<ref>PMID:25498144</ref> <ref>PMID:27499294</ref> <ref>PMID:21296186</ref> <ref>PMID:25540914</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Small-molecule tools have enabled mechanistic investigations and therapeutic targeting of the protein kinase-like (PKL) superfamily. However, such tools are still lacking for many PKL members, including the highly conserved and disease-related UbiB family. Here, we sought to develop and characterize an inhibitor for the archetypal UbiB member COQ8, whose function is essential for coenzyme Q (CoQ) biosynthesis. Guided by crystallography, activity assays and cellular CoQ measurements, we repurposed the 4-anilinoquinoline scaffold to selectively inhibit human COQ8A in cells. Our chemical tool promises to lend mechanistic insights into the activities of these widespread and understudied proteins and to offer potential therapeutic strategies for human diseases connected to their dysfunction.
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Authors:
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Small-molecule inhibition of the archetypal UbiB protein COQ8.,Murray NH, Asquith CRM, Fang Z, East MP, Ptak N, Smith RW, Vasta JD, Zimprich CA, Corona CR, Robers MB, Johnson GL, Bingman CA, Pagliarini DJ Nat Chem Biol. 2022 Oct 27. doi: 10.1038/s41589-022-01168-3. PMID:36302899<ref>PMID:36302899</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 7udq" 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: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Bingman CA]]
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[[Category: Murray N]]
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[[Category: Pagliarini DJ]]
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[[Category: Smith RW]]

Revision as of 07:17, 18 January 2023

Crystal structure of COQ8A-CA157 inhibitor complex in space group P1

PDB ID 7udq

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