6fy4
From Proteopedia
(Difference between revisions)
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<StructureSection load='6fy4' size='340' side='right'caption='[[6fy4]], [[Resolution|resolution]] 2.76Å' scene=''> | <StructureSection load='6fy4' size='340' side='right'caption='[[6fy4]], [[Resolution|resolution]] 2.76Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6fy4]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FY4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FY4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6fy4]] is a 4 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=6FY4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FY4 FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EAW:N-(2-bromophenyl)pyrrolidine-1-sulfonamide'>EAW</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EAW:N-(2-bromophenyl)pyrrolidine-1-sulfonamide'>EAW</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NQO1, DIA4, NMOR1 ([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/NAD(P)H_dehydrogenase_(quinone) NAD(P)H dehydrogenase (quinone)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.5.2 1.6.5.2] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(P)H_dehydrogenase_(quinone) NAD(P)H dehydrogenase (quinone)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.5.2 1.6.5.2] </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=6fy4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fy4 OCA], [http://pdbe.org/6fy4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fy4 RCSB], [http://www.ebi.ac.uk/pdbsum/6fy4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fy4 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=6fy4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fy4 OCA], [http://pdbe.org/6fy4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fy4 RCSB], [http://www.ebi.ac.uk/pdbsum/6fy4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fy4 ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/NQO1_HUMAN NQO1_HUMAN]] The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis. | [[http://www.uniprot.org/uniprot/NQO1_HUMAN NQO1_HUMAN]] The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | NAD(P)H:quinone oxidoreductase 1 (NQO1) is a human FAD-dependent enzyme that plays a crucial role in the antioxidant defense system. A naturally occurring single-nucleotide polymorphism (NQO1*2) in the NQO1 gene leads to an amino acid substitution (P187S), which severely compromises the activity and stability of the enzyme. The NQO1*2 genotype has been linked to a higher risk for several types of cancer and poor survival rate after anthracycline-based chemotherapy. In this study, we show that a small molecular chaperone (N-(2-bromophenyl)pyrrolidine-1-sulfonamide) repopulates the native wild-type conformation. As a consequence of the stabilizing effect, the enzymatic activity of the P187S variant protein is strongly improved in the presence of the molecular chaperone in vitro. | ||
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| + | A small molecule chaperone rescues the stability and activity of a cancer-associated variant of NAD(P)H:quinone oxidoreductase 1 in vitro.,Strandback E, Lienhart WD, Hromic-Jahjefendic A, Bourgeois B, Hogler A, Waltenstorfer D, Winkler A, Zangger K, Madl T, Gruber K, Macheroux P FEBS Lett. 2020 Feb;594(3):424-438. doi: 10.1002/1873-3468.13636. Epub 2019 Oct, 30. PMID:31605637<ref>PMID:31605637</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6fy4" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Gruber, K]] | [[Category: Gruber, K]] | ||
Current revision
Structure of human NAD(P) H:quinone oxidoreductase in complex with N-(2-bromophenyl)pyrrolidine-1-sulfonamide
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