NADH quinone oxidoreductase (NQO1) with inhibitor dicoumarol: Difference between revisions
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[http://en.wikipedia.org/wiki/NAD(P)H_dehydrogenase_(quinone) NAD(P)H quinone oxidoreductase 1] (NQO1, [http://www.expasy.org/cgi-bin/nicezyme.pl?1.6.5.2 EC 1.6.5.2]) is a ubiquitous [http://medical-dictionary.thefreedictionary.com/flavoenzyme flavoenzyme] that [http://en.wikipedia.org/wiki/Catalysis catalyzes] two electron reduction of [http://en.wikipedia.org/wiki/Quinone quinones] to [http://en.wikipedia.org/wiki/Hydroquinone hydroquinones] utilizing [[NAD(P)H]] as an [http://en.wikipedia.org/wiki/Electron_donor electron donor]. | [http://en.wikipedia.org/wiki/NAD(P)H_dehydrogenase_(quinone) NAD(P)H quinone oxidoreductase 1] (NQO1, [http://www.expasy.org/cgi-bin/nicezyme.pl?1.6.5.2 EC 1.6.5.2]) is a ubiquitous [http://medical-dictionary.thefreedictionary.com/flavoenzyme flavoenzyme] that [http://en.wikipedia.org/wiki/Catalysis catalyzes] two electron reduction of [http://en.wikipedia.org/wiki/Quinone quinones] to [http://en.wikipedia.org/wiki/Hydroquinone hydroquinones] utilizing [[NAD(P)H]] as an [http://en.wikipedia.org/wiki/Electron_donor electron donor]. | ||
NQO1 is a homo-dimer that functions via a “ping pong” mechanism. | NQO1 is a homo-dimer that functions via a “ping pong” mechanism. NAD(P)H binds to NQO1, reduces the [http://en.wikipedia.org/wiki/FAD FAD] co-factor and is then released, allowing the quinone substrate to bind the enzyme and to be reduced. The NAD(P)H and the quinone binding sites of NQO1 have a significant overlap, thus providing a molecular basis for this “ping pong” mechanism. | ||
Certain coumarins, flavones and the reactive dye cibacron blue are competitive inhibitors of NQO1 activity, which compete with NAD(P)H for binding to NQO1. [[Dicoumarol]] (3-3’–methylene-bis (4-hydroxycoumarin)),[[Image:Figure3 copy.jpg|border|center|300px]] is the most potent competitive inhibitor of NQO1. Dicoumarol competes with NAD(P)H for binding to NQO1 and prevents the electron transfer to FAD. | 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)),[[Image:Figure3 copy.jpg|border|center|300px]] is the most potent competitive inhibitor of NQO1. Dicoumarol competes with NAD(P)H for binding to NQO1 and prevents the 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 tumor suppressor p53 and several other short-lived proteins including [[p73α]] and ornithine decarboxylase ([[ODC]]). NQO1 binds and stabilizes [[p53]], protecting p53 from 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 tumor suppressor p53 and several other short-lived proteins including [[p73α]] and ornithine decarboxylase ([[ODC]]). NQO1 binds and stabilizes [[p53]], protecting p53 from 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. | ||
