1h69: Difference between revisions

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-[[Image:1h69.png|left|200px]]
-<!--
+==CRYSTAL STRUCTURE OF HUMAN NAD[P]H-QUINONE OXIDOREDUCTASE CO WITH 2,3,5,6,TETRAMETHYL-P-BENZOQUINONE (DUROQUINONE) AT 2.5 ANGSTROM RESOLUTION==
-The line below this paragraph, containing "STRUCTURE_1h69", creates the "Structure Box" on the page.
+<StructureSection load='1h69' size='340' side='right'caption='[[1h69]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1h69]] is a 4 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=1H69 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H69 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.86&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ARH:3-(HYDROXYMETHYL)-1-METHYL-5-(2-METHYLAZIRIDIN-1-YL)-2-PHENYL-1H-INDOLE-4,7-DIONE'>ARH</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></td></tr>
-{{STRUCTURE_1h69|  PDB=1h69  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1h69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h69 OCA], [https://pdbe.org/1h69 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h69 RCSB], [https://www.ebi.ac.uk/pdbsum/1h69 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h69 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://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.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h6/1h69_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1h69 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+BACKGROUND: NAD(P)H:quinone acceptor oxidoreductase (QR1) protects animal cells from the deleterious and carcinogenic effects of quinones and other electrophiles. Remarkably, the same enzyme activates cancer prodrugs that become cytotoxic only after two-electron reduction. QR1's ability to bioactivate quinones and its elevated expression in many human solid tumors makes this protein an excellent target for enzyme-directed drug development. Until now, structural analysis of the mode of binding of chemotherapeutic compounds to QR1 was based on model building using the structures of complexes with simple substrates; no structure of complexes of QR1 with chemotherapeutic prodrugs had been reported. RESULTS: Here we report the high-resolution crystal structures of complexes of QR1 with three chemotherapeutic prodrugs: RH1, a water-soluble homolog of dimethylaziridinylbenzoquinone; EO9, an aziridinylindolequinone; and ARH019, another aziridinylindolequinone. The structures, determined to resolutions of 2.0 A, 2.5 A, and 1.86 A, respectively, were refined to R values below 21% with excellent geometry. CONCLUSIONS: The structures show that compounds can bind to QR1 in more than one orientation. Surprisingly, the two aziridinylindolequinones bind to the enzyme in different orientations. The results presented here reveal two new factors that must be taken into account in the design of prodrugs targeted for activation by QR1: the enzyme binding site is highly plastic and changes to accommodate binding of different substrates, and homologous drugs with different substituents may bind to QR1 in different orientations. These structural insights provide important clues for the optimization of chemotherapeutic compounds that utilize this reductive bioactivation pathway.
-===CRYSTAL STRUCTURE OF HUMAN NAD[P]H-QUINONE OXIDOREDUCTASE CO WITH 2,3,5,6,TETRAMETHYL-P-BENZOQUINONE (DUROQUINONE) AT 2.5 ANGSTROM RESOLUTION===
+Structure-based development of anticancer drugs: complexes of NAD(P)H:quinone oxidoreductase 1 with chemotherapeutic quinones.,Faig M, Bianchet MA, Winski S, Hargreaves R, Moody CJ, Hudnott AR, Ross D, Amzel LM Structure. 2001 Aug;9(8):659-67. PMID:11587640<ref>PMID:11587640</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1h69" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_11587640}}, adds the Publication Abstract to the page
+*[[Quinone reductase 3D structures|Quinone reductase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 11587640 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_11587640}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[1h69]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H69 OCA].
-==Reference==
-<ref group="xtra">PMID:11587640</ref><ref group="xtra">PMID:10706635</ref><ref group="xtra">PMID:10917652</ref><ref group="xtra">PMID:10433694</ref><ref group="xtra">PMID:7568029</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Amzel, L M.]]
+[[Category: Large Structures]]
-[[Category: Bianchet, M A.]]
+[[Category: Amzel LM]]
-[[Category: Chen, S.]]
+[[Category: Bianchet MA]]
-[[Category: Faig, M.]]
+[[Category: Chen S]]
-[[Category: Ross, D.]]
+[[Category: Faig M]]
-[[Category: Winski, S.]]
+[[Category: Ross D]]
-[[Category: Flavoprotein]]
+[[Category: Winski S]]
-[[Category: Oxidoreductase]]
-[[Category: Rossman fold]]