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[[Image:2bzs.gif|left|200px]]
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{{STRUCTURE_2bzs|  PDB=2bzs  |  SCENE=  }}
'''BINDING OF ANTI-CANCER PRODRUG CB1954 TO THE ACTIVATING ENZYME NQO2 REVEALED BY THE CRYSTAL STRUCTURE OF THEIR COMPLEX.'''


==Binding of anti-cancer prodrug CB1954 to the activating enzyme NQO2 revealed by the crystal structure of their complex.==
<StructureSection load='2bzs' size='340' side='right'caption='[[2bzs]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2bzs]] 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=2BZS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BZS 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]] 2&#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=2bzs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bzs OCA], [https://pdbe.org/2bzs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bzs RCSB], [https://www.ebi.ac.uk/pdbsum/2bzs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bzs 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/bz/2bzs_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=2bzs ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
CB1954 is an attractive prodrug for directed-enzyme prodrug therapy (DEPT) and a conventional prodrug against tumors in which the enzyme NQO2 is highly expressed. We have determined the crystal structure of the NQO2-CB1954 complex to 2.0 A resolution. The binding of the prodrug is governed by hydrophobic forces, while two key electrostatic contacts determine the specific orientation of the ligand. The structure also reveals an unfavorable interaction, therefore suggesting possible avenues for DEPT-tailored engineering studies.


==Overview==
Binding of the anticancer prodrug CB1954 to the activating enzyme NQO2 revealed by the crystal structure of their complex.,AbuKhader M, Heap J, De Matteis C, Kellam B, Doughty SW, Minton N, Paoli M J Med Chem. 2005 Dec 1;48(24):7714-9. PMID:16302811<ref>PMID:16302811</ref>
CB1954 is an attractive prodrug for directed-enzyme prodrug therapy (DEPT) and a conventional prodrug against tumors in which the enzyme NQO2 is highly expressed. We have determined the crystal structure of the NQO2-CB1954 complex to 2.0 A resolution. The binding of the prodrug is governed by hydrophobic forces, while two key electrostatic contacts determine the specific orientation of the ligand. The structure also reveals an unfavorable interaction, therefore suggesting possible avenues for DEPT-tailored engineering studies.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
2BZS is a [[Single protein]] structure of 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=2BZS OCA].
</div>
<div class="pdbe-citations 2bzs" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Binding of the anticancer prodrug CB1954 to the activating enzyme NQO2 revealed by the crystal structure of their complex., AbuKhader M, Heap J, De Matteis C, Kellam B, Doughty SW, Minton N, Paoli M, J Med Chem. 2005 Dec 1;48(24):7714-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16302811 16302811]
*[[Quinone reductase 3D structures|Quinone reductase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Doughty, S W.]]
[[Category: Abu Khader MM]]
[[Category: Heap, J T.]]
[[Category: De Matteis C]]
[[Category: Kellam, B.]]
[[Category: Doughty SW]]
[[Category: Khader, M M.Abu.]]
[[Category: Heap JT]]
[[Category: Matteis, C De.]]
[[Category: Kellam B]]
[[Category: Minton, N.]]
[[Category: Minton N]]
[[Category: Paoli, M.]]
[[Category: Paoli M]]
[[Category: Cb1954]]
[[Category: Fad]]
[[Category: Flavoprotein]]
[[Category: Metal-binding]]
[[Category: Nqo2]]
[[Category: Oxidoreductase]]
[[Category: Polymorphism]]
[[Category: Zinc]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 21:01:41 2008''
Retrieved from "https://proteopedia.org/2bzs"