NADH quinone oxidoreductase (NQO1) with inhibitor dicoumarol: Difference between revisions
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NAD(P)H quinone oxidoreductase 1 (NQO1) is a ubiquitous flavoenzyme that catalyzes two electron reduction of quinones to hydroquinones utilizing [[NAD(P)H]] as an electron donor. | NAD(P)H quinone oxidoreductase 1 (NQO1) is a ubiquitous flavoenzyme that catalyzes two electron reduction of quinones to hydroquinones utilizing [[NAD(P)H]] as an electron donor. | ||
NQO1 is a homo-dimer that functions via a “ping pong” mechanism. NAD(P)H binds to NQO1, reduces the [[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. | NQO1 is a homo-dimer that functions via a “ping pong” mechanism. NAD(P)H binds to NQO1, reduces the [[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: | 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. | ||
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. | ||
