1qrd
From Proteopedia
(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...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1qrd.gif|left|200px]]<br /><applet load="1qrd" size=" | + | [[Image:1qrd.gif|left|200px]]<br /><applet load="1qrd" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1qrd, resolution 2.4Å" /> | caption="1qrd, resolution 2.4Å" /> | ||
'''QUINONE REDUCTASE/FAD/CIBACRON BLUE/DUROQUINONE COMPLEX'''<br /> | '''QUINONE REDUCTASE/FAD/CIBACRON BLUE/DUROQUINONE COMPLEX'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Quinone reductase [NAD(P)H:(quinone acceptor) oxidoreductase, EC | + | 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== | ==About this Structure== | ||
| - | 1QRD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_rattus Rattus rattus] with FAD, CBD and DQN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/NAD(P)H_dehydrogenase_(quinone) NAD(P)H dehydrogenase (quinone)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.5.2 1.6.5.2] Full crystallographic information is available from [http:// | + | 1QRD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_rattus Rattus rattus] with <scene name='pdbligand=FAD:'>FAD</scene>, <scene name='pdbligand=CBD:'>CBD</scene> and <scene name='pdbligand=DQN:'>DQN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/NAD(P)H_dehydrogenase_(quinone) NAD(P)H dehydrogenase (quinone)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.6.5.2 1.6.5.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QRD OCA]. |
==Reference== | ==Reference== | ||
| Line 14: | Line 14: | ||
[[Category: Rattus rattus]] | [[Category: Rattus rattus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Amzel, L | + | [[Category: Amzel, L M.]] |
| - | [[Category: Bianchet, M | + | [[Category: Bianchet, M A.]] |
[[Category: Li, R.]] | [[Category: Li, R.]] | ||
[[Category: Talalay, P.]] | [[Category: Talalay, P.]] | ||
| Line 25: | Line 25: | ||
[[Category: quinone-reductase (cytosolic)]] | [[Category: quinone-reductase (cytosolic)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:42:52 2008'' |
Revision as of 12:42, 21 February 2008
|
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 , and 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
Page seeded by OCA on Thu Feb 21 14:42:52 2008
