NADH quinone oxidoreductase (NQO1) with inhibitor dicoumarol: Difference between revisions
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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. | ||
The crystal structure of human | The crystal structure of human <scene name='Nqo1/Nqo1_1/1'> NQO1</scene> in complex with dicoumarol was determine at 2.75 Å resolution. | ||
NQO1 is a physiological homodimer composed of two interlocked monomers. Each monomer is composed of two domains: a large catalytic domain with α/β fold with flavodoxin topology (residues 1-220) and a small C-terminal domain (residues 221-273). Two catalytic sites are formed and are present at the dimer interface. Two FAD molecules (red) are present; each one is bound to the catalytic domain of each monomer. The dicoumarol molecule (purple) is bound to each of the catalytic sites interacting with FAD and with residues from both monomer.The dicoumarol molecule is bound to each of the catalytic sites interacting with FAD and with residues from both monomers. | NQO1 is a physiological homodimer composed of two interlocked monomers. Each monomer is composed of two domains: a large catalytic domain with α/β fold with flavodoxin topology (residues 1-220) and a small C-terminal domain (residues 221-273). Two catalytic sites are formed and are present at the dimer interface. Two FAD molecules (red) are present; each one is bound to the catalytic domain of each monomer. The dicoumarol molecule (purple) is bound to each of the catalytic sites interacting with FAD and with residues from both monomer.The dicoumarol molecule is bound to each of the catalytic sites interacting with FAD and with residues from both monomers. | ||
[[Image:NQO_Dic copy.jpg|border|center|300px]] | [[Image:NQO_Dic copy.jpg|border|center|300px]] | ||