1xi2: Difference between revisions

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-[[Image:1xi2.jpg|left|200px]]<br /><applet load="1xi2" size="350" color="white" frame="true" align="right" spinBox="true"
-caption="1xi2, resolution 1.5&Aring;" />
-'''Quinone Reductase 2 in Complex with Cancer Prodrug CB1954'''<br />
-==Overview==
+==Quinone Reductase 2 in Complex with Cancer Prodrug CB1954==
-CB1954 is a cancer pro-drug that can be activated through reduction by Escherichia coli nitro-reductases and quinone reductases. Human quinone reductase 2 is very efficient in the activation of CB1954, approximately 3000 times more efficient than human QR1 in terms of k(cat)/K(m). We have solved the three-dimensional structure of QR2 in complex with CB1954 to a nominal resolution of 1.5A. The complex structure indicates the essentiality of the two nitro groups: one nitro group forms hydrogen bonds with the side-chain of Asn161 of QR2 to hold the other nitro group in position for the reduction. We further conclude that residue 161, an Asn in QR2 and a His in QR1, is critical in differentiating the substrate specificities of these two enzymes. Mutation of Asn161 to His161 in QR2 resulted in the total loss of the enzymatic activity towards activation of CB1954, whereas the rates of reduction towards menadione are not altered.
+<StructureSection load='1xi2' size='340' side='right'caption='[[1xi2]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1xi2]] 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=1XI2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XI2 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]] 1.5&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CB1:5-(AZIRIDIN-1-YL)-2,4-DINITROBENZAMIDE'>CB1</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=1xi2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xi2 OCA], [https://pdbe.org/1xi2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xi2 RCSB], [https://www.ebi.ac.uk/pdbsum/1xi2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xi2 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>
+== 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/xi/1xi2_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=1xi2 ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-XI2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=FAD:'>FAD</scene> and <scene name='pdbligand=CB1:'>CB1</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XI2 OCA].
+*[[Quinone reductase 3D structures|Quinone reductase 3D structures]]
+== References ==
-==Reference==
+<references/>
-Crystal structure of quinone reductase 2 in complex with cancer prodrug CB1954., Fu Y, Buryanovskyy L, Zhang Z, Biochem Biophys Res Commun. 2005 Oct 14;336(1):332-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16129418 16129418]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Buryanovskyy, L.]]
+[[Category: Buryanovskyy L]]
-[[Category: Fu, Y.]]
+[[Category: Fu Y]]
-[[Category: Zhang, Z.]]
+[[Category: Zhang Z]]
-[[Category: CB1]]
-[[Category: FAD]]
-[[Category: ZN]]
-[[Category: cb1954]]
-[[Category: qr2]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:54:59 2008''