3tem: Difference between revisions
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[[ | ==Quinone Oxidoreductase (NQ02) bound to the imidazoacridin-6-one 6a1== | ||
<StructureSection load='3tem' size='340' side='right' caption='[[3tem]], [[Resolution|resolution]] 1.45Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3tem]] is a 2 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=3TEM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TEM FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6A1:HYDROXY(2-{[(5S)-6-HYDROXY-8-METHOXY-4,5-DIHYDRO-3H-IMIDAZO[4,5,1-DE]ACRIDIN-5-YL]AMINO}ETHYL)DIMETHYLAMMONIUM'>6A1</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</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">[[3te7|3te7]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NQO2, NMOR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3tem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tem OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tem RCSB], [http://www.ebi.ac.uk/pdbsum/3tem PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Imidazoacridin-6-ones are shown to be potent nanomolar inhibitors of the enzyme NQO2. By use of computational molecular modeling, a reliable QSAR was established, relating inhibitory potency with calculated binding affinity. Further, crystal structures of NQO2 containing two of the imidazoacridin-6-ones have been solved. To generate compounds with reduced off-target (DNA binding) effects, an N-oxide moiety was introduced into the tertiary aminoalkyl side chain of the imidazoacridin-6-ones. This resulted in substantially less toxicity in a panel of eight cancer cell lines, decreased protein binding, and reduced DNA binding and nuclear accumulation. Finally, one of the N-oxides showed potent ability to inhibit the enzymatic function of NQO2 in cells, and therefore, it may be useful as a pharmacological probe to study the properties of the enzyme in vitro and in vivo. | |||
Novel Inhibitors of NRH:Quinone Oxidoreductase 2 (NQO2): Crystal Structures, Biochemical Activity, and Intracellular Effects of Imidazoacridin-6-ones.,Dunstan MS, Barnes J, Humphries M, Whitehead RC, Bryce RA, Leys D, Stratford IJ, Nolan KA J Med Chem. 2011 Sep 13. PMID:21859103<ref>PMID:21859103</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Quinone reductase|Quinone reductase]] | *[[Quinone reductase|Quinone reductase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Dunstan, M S | [[Category: Dunstan, M S]] | ||
[[Category: Leys, D | [[Category: Leys, D]] | ||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | ||
Revision as of 17:19, 9 December 2014
Quinone Oxidoreductase (NQ02) bound to the imidazoacridin-6-one 6a1
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