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Quinone reductase: Difference between revisions

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<StructureSection load='2f1o.pdb' size='450' scene='2f1o/Com_view/2'  caption='NADPH dehydrogenase complex with FAD (red) and dicoumarol (blue) [[2f1o]]'>
<StructureSection load='' size='350' scene='2f1o/Com_view/2'  caption='NADPH dehydrogenase complex with FAD (red) and dicoumarol (blue) [[2f1o]]'>
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'''Quinone reductase type 1 (QR1)''' reduces quinines to the non-toxic hydroquinone. '''Quinone reductase type 2 (QR2)''' catalyzes the reduction of adrenochrome.    The '''sulfide-quinone reductase (SQR)''' reduces sulfide and thus provides electrons for phototropic processes in bacteria. '''NADPH-quinone reductase (NQR)''' catalyzes the reduction of quinone to semiquinone. The images at the left and at the right correspond to one representative Quinone reductase, ''i.e.'' the crystal structure of NADH quinone oxidoreductase (NQO1) with inhibitor dicoumarol ([[2f1o]]).
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==Function==
*'''Quinone reductase type 1 (QR1)''' reduces quinines to the non-toxic hydroquinone.  
*'''Quinone reductase type 2 (QR2)''' or '''ribosyldihydronicotinamide dehydrogenase [quinone]''' catalyzes the reduction of adrenochrome.     
* '''Sulfide-quinone reductase (SQR)''' reduces sulfide and thus provides electrons for phototropic processes in bacteria.  
* '''NADPH-quinone reductase (NQR)''' catalyzes the reduction of quinone to semiquinone.  
*'''Na(+)-translocating NADH-quinone reductase''' is the Na(+) pumping respiratory complex found in prokaryotes<ref>PMID:25052842</ref>. 
See [[Electron Transport & Oxidative Phosphorylation]].


== NADH Quinone oxidoreductase type 1 (NQO1) in complex with its potent inhibitor dicoumarol ==
== NADH Quinone oxidoreductase type 1 (NQO1) in complex with its potent inhibitor dicoumarol ==
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Certain [http://en.wikipedia.org/wiki/Coumarin coumarins], [http://en.wikipedia.org/wiki/Flavones flavones] and the reactive dye cibacron blue are [http://en.wikipedia.org/wiki/Competitive_inhibition competitive inhibitors] of NQO1 activity, which compete with NAD(P)H for binding to NQO1. [[Dicoumarol]] (3-3’–methylene-bis (4-hydroxycoumarin)),
Certain [http://en.wikipedia.org/wiki/Coumarin coumarins], [http://en.wikipedia.org/wiki/Flavones flavones] and the reactive dye cibacron blue are [http://en.wikipedia.org/wiki/Competitive_inhibition competitive inhibitors] of NQO1 activity, which compete with NAD(P)H for binding to NQO1. [[Dicoumarol]] (3-3’–methylene-bis (4-hydroxycoumarin)),
is the most potent competitive inhibitor of NQO1. Dicoumarol competes with NAD(P)H for binding to NQO1 and prevents the [http://en.wikipedia.org/wiki/Electron_transfer electron transfer] to FAD.
is the most potent competitive inhibitor of NQO1. Dicoumarol competes with NAD(P)H for binding to NQO1 and prevents the [http://en.wikipedia.org/wiki/Electron_transfer electron transfer] to FAD.
In addition to its role in the detoxification of quinones, NQO1 is also a 20S proteasome-associated protein that plays an important role in the stability of the [http://en.wikipedia.org/wiki/Tumor_suppressor_gene tumor suppressor] p53 and several other short-lived proteins including [[p73α]] and ornithine decarboxylase (ODC, ''i.e.'' [[7odc]]). NQO1 binds and stabilizes [[p53]], protecting p53 from [http://en.wikipedia.org/wiki/Proteasome#Ubiquitin-independent_degradation ubiquitin-independent 20S proteasomal degradation]. Dicoumarol and several other inhibitors of NQO1 activity, which compete with NADH for binding to NQO1, disrupt the binding of NQO1 to p53 and induce ubiquitin-independent p53 degradation.
In addition to its role in the detoxification of quinones, NQO1 is also a 20S proteasome-associated protein that plays an important role in the stability of the [http://en.wikipedia.org/wiki/Tumor_suppressor_gene tumor suppressor] p53 and several other short-lived proteins including p73α and ornithine decarboxylase (ODC, ''i.e.'' [[7odc]]). NQO1 binds and stabilizes [[p53]], protecting p53 from [http://en.wikipedia.org/wiki/Proteasome#Ubiquitin-independent_degradation ubiquitin-independent 20S proteasomal degradation]. Dicoumarol and several other inhibitors of NQO1 activity, which compete with NADH for binding to NQO1, disrupt the binding of NQO1 to p53 and induce ubiquitin-independent p53 degradation.


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The quinone ES936 causes irreversible inhibition of the NQO1. <scene name='2f1o/Align2/5'>Alignment</scene> of the hNQO1 dimer in complex with <font color='red'><b>ES936 (red)</b></font> ([[1kbq]]) with the hNQO1−dicoumarol complex ([[2f1o]]) yields 0.45Å RMSD for the 546 Cα atoms. The ES936 causes structural change only in the position of Phe 232. The movement of this residue is smaller than that caused by dicoumarol. The <scene name='2f1o/Align2/6'>distance</scene> between Tyr 128 and Phe 232 in the hNQO1−ES936 complex is only ~7 Å, while in the hNQO1−dicoumarol complex it is ~12 Å.
The quinone ES936 causes irreversible inhibition of the NQO1. <scene name='2f1o/Align2/5'>Alignment</scene> of the hNQO1 dimer in complex with <font color='red'><b>ES936 (red)</b></font> ([[1kbq]]) with the hNQO1−dicoumarol complex ([[2f1o]]) yields 0.45Å RMSD for the 546 Cα atoms. The ES936 causes structural change only in the position of Phe 232. The movement of this residue is smaller than that caused by dicoumarol. The <scene name='2f1o/Align2/6'>distance</scene> between Tyr 128 and Phe 232 in the hNQO1−ES936 complex is only ~7 Å, while in the hNQO1−dicoumarol complex it is ~12 Å.
</StructureSection>


== 3D Structures of Quinone reductase ==
== 3D Structures of Quinone reductase ==


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
[[Quinone reductase 3D structures]]
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*Quinone reductase type 1
 
**[[3jsx]] – hQR1 + coumarine derivative<br />
**[[2f1o]] – hQR1 + dicoumarol<br />
**[[1kbo]], [[1kbq]] – hQR1 + indole derivative<br />
 
*Quinone reductase type 2
 
**[[3fw1]], [[1qr2]] – hQR2 - human<br />
**[[3o2n]], [[3g5m]], [[3gam]] – hQR2 + PET agent<br />
**[[3ovm]], [[3owh]], [[3owx]] – hQR2 + carbamate derivative<br />
**[[3ox1]], [[2qx4]], [[2qx6]], [[2qx8]], [[2qx9]], [[2qwx]] – hQR2 + acetamide derivative<br />
**[[3ox2]] - hQR2 + indole derivative<br />
**[[3ox3]] - hQR2 + carboxamide derivative<br />
**[[2qmy]] – hQR2 + adrenochrome<br />
**[[2qr2]] – hQR2 + menadione<br />
**[[2qmz]] – hQR2 + dopamine<br />
**[[1sg0]] – hQR2 + resveratol<br />
**[[3nhu]], [[3nhs]], [[3nhr]], [[3nhp]], [[3nhl]], [[3nhk]], [[3nhj]], [[3nhf]], [[3nfr]], [[3nhw]], [[3nhy]], [[3uxe]], [[3uxh]] - hQR2 + quinoline derivative<br />
**[[3te7]], [[3tem]], [[3tzb]] – hQR2 + acridine derivative<br />
**[[2bzs]], [[1xi2]], [[1zx1]], [[3o73]] – hQR2 + anti-cancer prodrug<br />
**[[4fgj]], [[4fgk]], [[4fgl]] – hQR2 + anti-malaria drug<br />
**[[4gqi]], [[4gr9]] – hQR2 + ligand<br />
 
*Sulfide-quinone reductase
 
**[[3hyv]] – AaSQR – ''Aquifex aeolicus''<br />
**[[3hyw]] – AaSQR + decylubiquinone<br />
**[[3hyx]] – AaSQR + Aurachin C<br />
 
*NADPH-quinone reductase
 
**[[3ha2]] – NQR – ''Pediococcus pentosaceus''<br />
**[[1dxq]], [[1d4a]] - hNQR<br />
**[[1yb5]] – hNQR + NADP<br />
**[[1gg5]], [[1h66]], [[1h69]], [[1qbg]] - hNQR + anti-cancer prodrug<br />
**[[1dxo]] - hNQR + quinone derivative<br />
 
*Quinone reductase


**[[1qrd]] – QR + bicarbon blue + duroquinone - rat<br />
**[[4gi5]] – QR + FAD – ''Klebsiella pneumoniae''
}}
==References==
==References==
<ref group="xtra">PMID:10706635</ref> <ref group="xtra">PMID:16700548</ref> <references group="xtra"/>
<ref group="xtra">PMID:10706635</ref> <ref group="xtra">PMID:16700548</ref> <references group="xtra"/>
 
<references/>
</StructureSection>
[[Category:Topic Page]]
[[Category:Topic Page]]

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Alexander Berchansky, Michal Harel, Joel L. Sussman
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