4xdh: Difference between revisions
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==Crystal Structure of Quinone Reductase II in complex with a 2-(4-methoxy-phenyl)-5-methoxy-indol-3-one molecule== | ==Crystal Structure of Quinone Reductase II in complex with a 2-(4-methoxy-phenyl)-5-methoxy-indol-3-one molecule== | ||
<StructureSection load='4xdh' size='340' side='right' caption='[[4xdh]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='4xdh' size='340' side='right'caption='[[4xdh]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4xdh]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XDH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XDH FirstGlance]. <br> | <table><tr><td colspan='2'>[[4xdh]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XDH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XDH FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3ZV:5-METHOXY-2-(4-METHOXYPHENYL)-3H-INDOL-3-ONE'>3ZV</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> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3ZV:5-METHOXY-2-(4-METHOXYPHENYL)-3H-INDOL-3-ONE'>3ZV</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NQO2, NMOR2 ([http://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'>[http://en.wikipedia.org/wiki/Ribosyldihydronicotinamide_dehydrogenase_(quinone) Ribosyldihydronicotinamide dehydrogenase (quinone)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.10.99.2 1.10.99.2] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ribosyldihydronicotinamide_dehydrogenase_(quinone) Ribosyldihydronicotinamide dehydrogenase (quinone)], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4xdh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xdh OCA], [http://pdbe.org/4xdh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xdh RCSB], [http://www.ebi.ac.uk/pdbsum/4xdh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xdh ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4xdh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xdh OCA], [http://pdbe.org/4xdh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xdh RCSB], [http://www.ebi.ac.uk/pdbsum/4xdh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xdh ProSAT]</span></td></tr> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Boutin, J A]] | [[Category: Boutin, J A]] | ||
[[Category: Ferry, G]] | [[Category: Ferry, G]] | ||
Revision as of 10:08, 29 May 2019
Crystal Structure of Quinone Reductase II in complex with a 2-(4-methoxy-phenyl)-5-methoxy-indol-3-one moleculeCrystal Structure of Quinone Reductase II in complex with a 2-(4-methoxy-phenyl)-5-methoxy-indol-3-one molecule
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 PubMedIndolone-N-oxides have antiplasmodial properties against Plasmodium falciparum at the erythrocytic stage, with IC50 values in the nanomolar range. The mechanism of action of indolone derivatives involves the production of free radicals, which follows their bioreduction by an unknown mechanism. In this study, we hypothesized that human quinone reductase 2 (hQR2), known to act as a flavin redox switch upon binding to the broadly used antimalarial chloroquine, could be involved in the activity of the redox-active indolone derivatives. Therefore, we investigated the role of hQR2 in the reduction of indolone derivatives. We analyzed the interaction between hQR2 and several indolone-type derivatives by examining enzymatic kinetics, the substrate/protein complex structure with X-ray diffraction analysis, and the production of free radicals with electron paramagnetic resonance. The reduction of each compound in cells overexpressing hQR2 was compared to its reduction in naive cells. This process could be inhibited by the specific hQR2 inhibitor, S29434. These results confirmed that the anti-malarial activity of indolone-type derivatives was linked to their ability to serve as hQR2 substrates and not as hQR2 inhibitors as reported for chloroquine, leading to the possibility that substrate of hQR2 could be considered as a new avenue for the design of new antimalarial compounds. Role of Quinone Reductase 2 in the Antimalarial Properties of Indolone-Type Derivatives.,Cassagnes LE, Rakotoarivelo N, Sirigu S, Perio P, Najahi E, Chavas LM, Thompson A, Gayon R, Ferry G, Boutin JA, Valentin A, Reybier K, Nepveu F Molecules. 2017 Jan 30;22(2). pii: E210. doi: 10.3390/molecules22020210. PMID:28146103[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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