3o73: Difference between revisions
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==Crystal structure of quinone reductase 2 in complex with the indolequinone MAC627== | ==Crystal structure of quinone reductase 2 in complex with the indolequinone MAC627== | ||
<StructureSection load='3o73' size='340' side='right' caption='[[3o73]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='3o73' size='340' side='right'caption='[[3o73]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3o73]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3o73]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O73 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O73 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=O73:5-[(4-AMINOBUTYL)AMINO]-1,2-DIMETHYL-3-[(4-NITROPHENOXY)METHYL]-1H-INDOLE-4,7-DIONE'>O73</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=O73:5-[(4-AMINOBUTYL)AMINO]-1,2-DIMETHYL-3-[(4-NITROPHENOXY)METHYL]-1H-INDOLE-4,7-DIONE'>O73</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1qr2|1qr2]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1qr2|1qr2]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NQO2, NMOR2 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NQO2, NMOR2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Ribosyldihydronicotinamide_dehydrogenase_(quinone) Ribosyldihydronicotinamide dehydrogenase (quinone)], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.10.99.2 1.10.99.2] </span></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=3o73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o73 OCA], [https://pdbe.org/3o73 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o73 RCSB], [https://www.ebi.ac.uk/pdbsum/3o73 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o73 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Colucci, M A]] | [[Category: Colucci, M A]] | ||
[[Category: Dufour, M]] | [[Category: Dufour, M]] | ||
Revision as of 10:17, 12 May 2022
Crystal structure of quinone reductase 2 in complex with the indolequinone MAC627Crystal structure of quinone reductase 2 in complex with the indolequinone MAC627
Structural highlights
Function[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.[1] Publication Abstract from PubMedA role for the flavoprotein NRH:quinone oxidoreductase 2 (NQO2, QR2) in human diseases such as malaria, leukemia and neurodegeneration has been proposed. In order to explore the potential of NQO2 as a therapeutic target, we have developed potent and selective mechanism-based inhibitors centered on the indolequinone pharmacophore. The compounds show remarkable selectivity for NQO2 over the closely related flavoprotein NQO1, with small structural changes defining selectivity. Biochemical studies confirmed the mechanism-based inhibition, whereas X-ray crystallography and mass spectrometry revealed the nature of the inhibitor interaction with the protein. These indolequinones represent the first mechanism-based inhibitors of NQO2, and their novel mode of action involving alkylation of the flavin cofactor, provides significant advantages over existing competitive inhibitors in terms of potency and irreversibility, and will open new opportunities to define the role of NQO2 in disease. Mechanism-Based Inhibition of Quinone Reductase 2 (NQO2): Selectivity for NQO2 over NQO1 and Structural Basis for Flavoprotein Inhibition.,Dufour M, Yan C, Siegel D, Colucci MA, Jenner M, Oldham NJ, Gomez J, Reigan P, Li Y, De Matteis CI, Ross D, Moody CJ Chembiochem. 2011 Apr 19. doi: 10.1002/cbic.201100085. PMID:21506232[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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