View source for 5lbz


==Structure of the human quinone reductase 2 (NQO2) in complex with pacritinib==
<StructureSection load='5lbz' size='340' side='right'caption='[[5lbz]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5lbz]] 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=5LBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LBZ 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]] 1.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6T3:11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene'>6T3</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5lbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lbz OCA], [https://pdbe.org/5lbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lbz RCSB], [https://www.ebi.ac.uk/pdbsum/5lbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lbz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NQO2_HUMAN NQO2_HUMAN] The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.<ref>PMID:18254726</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the target spectrum of 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on the "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration of phosphoproteomic data refined drug-affected pathways, identified response markers, and strengthened rationale for combination treatments. We exemplify translational value by discovering SIK2 (salt-inducible kinase 2) inhibitors that modulate cytokine production in primary cells, by identifying drugs against the lung cancer survival marker MELK (maternal embryonic leucine zipper kinase), and by repurposing cabozantinib to treat FLT3-ITD-positive acute myeloid leukemia. This resource, available via the ProteomicsDB database, should facilitate basic, clinical, and drug discovery research and aid clinical decision-making.

The target landscape of clinical kinase drugs.,Klaeger S, Heinzlmeir S, Wilhelm M, Polzer H, Vick B, Koenig PA, Reinecke M, Ruprecht B, Petzoldt S, Meng C, Zecha J, Reiter K, Qiao H, Helm D, Koch H, Schoof M, Canevari G, Casale E, Depaolini SR, Feuchtinger A, Wu Z, Schmidt T, Rueckert L, Becker W, Huenges J, Garz AK, Gohlke BO, Zolg DP, Kayser G, Vooder T, Preissner R, Hahne H, Tonisson N, Kramer K, Gotze K, Bassermann F, Schlegl J, Ehrlich HC, Aiche S, Walch A, Greif PA, Schneider S, Felder ER, Ruland J, Medard G, Jeremias I, Spiekermann K, Kuster B Science. 2017 Dec 1;358(6367). pii: 358/6367/eaan4368. doi:, 10.1126/science.aan4368. PMID:29191878<ref>PMID:29191878</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5lbz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Quinone reductase 3D structures|Quinone reductase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kuster B]]
[[Category: Medard G]]
[[Category: Schneider S]]