View source for 4zvm


==Oxidized quinone reductase 2 in complex with doxorubicin==
<StructureSection load='4zvm' size='340' side='right' caption='[[4zvm]], [[Resolution|resolution]] 1.97&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zvm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZVM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZVM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DM2:DOXORUBICIN'>DM2</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4zvk|4zvk]], [[4zvl|4zvl]], [[4zvn|4zvn]]</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=4zvm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zvm OCA], [http://pdbe.org/4zvm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zvm RCSB], [http://www.ebi.ac.uk/pdbsum/4zvm PDBsum]</span></td></tr>
</table>
== Function ==
[[http://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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Quinone reductase 2 (NQO2) is an enzyme that might have intracellular signaling functions. NQO2 can exist in either an oxidized state or a reduced state, and binding of compounds to one or both of these states inhibits enzymatic activity and could also affect intracellular signaling. A wide range of planar aromatic compounds bind NQO2, and we have identified three DNA-intercalating agents [ethidium bromide, acridine orange (AO), and doxorubicin] as novel nanomolar inhibitors of NQO2. Ethidium and AO, which carry a positive charge in their aromatic ring systems, bound reduced NQO2 with an affinity 50-fold higher than that of oxidized NQO2, while doxorubicin bound only oxidized NQO2. Crystallographic analyses of oxidized NQO2 in complex with the inhibitors indicated that the inhibitors were situated deep in the active site. The aromatic faces were sandwiched between the isoalloxazine ring of FAD and the phenyl ring of F178, with their edges making direct contact with residues lining the active site. In reduced NQO2, ethidium and AO occupied a more peripheral position in the active site, allowing several water molecules to interact with the polar end of the negatively charged isoalloxazine ring. We also showed that AO inhibited NQO2 at a nontoxic concentration in cells while ethidium was less effective at inhibiting NQO2 in cells. Together, this study shows that reduced NQO2 has structural and electrostatic properties that yield a preference for binding of planar, aromatic, and positively charged molecules that can also function as DNA-intercalating agents.

Binding of DNA-Intercalating Agents to Oxidized and Reduced Quinone Reductase 2.,Leung KK, Shilton BH Biochemistry. 2015 Dec 29;54(51):7438-48. doi: 10.1021/acs.biochem.5b00884. Epub , 2015 Dec 14. PMID:26636353<ref>PMID:26636353</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zvm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Leung, K K]]
[[Category: Shilton, B H]]
[[Category: Doxorubicin]]
[[Category: Oxidoreductase-inhibitor complex]]
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
[[Category: Quinone reductase 2]]