1qrd
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(New page: 200px<br /><applet load="1qrd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qrd, resolution 2.4Å" /> '''QUINONE REDUCTASE/FAD...)
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Revision as of 22:47, 20 November 2007
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QUINONE REDUCTASE/FAD/CIBACRON BLUE/DUROQUINONE COMPLEX
Overview
Quinone reductase [NAD(P)H:(quinone acceptor) oxidoreductase, EC, 1.6.99.2], also called DT diaphorase, is a homodimeric FAD-containing, enzyme that catalyzes obligatory NAD(P)H-dependent two-electron reductions, of quinones and protects cells against the toxic and neoplastic effects of, free radicals and reactive oxygen species arising from one-electron, reductions. These two-electron reductions participate in the reductive, bioactivation of cancer chemotherapeutic agents such as mitomycin C in, tumor cells. Thus, surprisingly, the same enzymatic reaction that protects, normal cells activates cytotoxic drugs used in cancer chemotherapy. The, 2.1-A crystal structure of rat liver quinone reductase reveals that the, folding of a portion of each monomer is similar to that of flavodoxin, a, bacterial FMN-containing protein. Two additional portions of the, polypeptide chains are involved in dimerization and in formation of the, two identical catalytic sites to which both monomers contribute. The, crystallographic structures of two FAD-containing enzyme complexes (one, containing NADP+, the other containing duroquinone) suggest that direct, hydride transfers from NAD(P)H to FAD and from FADH2 to the quinone [which, occupies the site vacated by NAD(P)H] provide a simple rationale for the, obligatory two-electron reductions involving a ping-pong mechanism.
About this Structure
1QRD is a Single protein structure of sequence from Rattus rattus with FAD, CBD and DQN as ligands. Active as NAD(P)H dehydrogenase (quinone), with EC number 1.6.5.2 Full crystallographic information is available from OCA.
Reference
The three-dimensional structure of NAD(P)H:quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two-electron reduction., Li R, Bianchet MA, Talalay P, Amzel LM, Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8846-50. PMID:7568029
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