NADH quinone oxidoreductase (NQO1) with inhibitor dicoumarol: Difference between revisions

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]]

The different residues of NQO1 interacting with dicoumarol with and the conformational changes imposed upon dicoumarol binding. The most prominent conformational changes that occur in the presence of dicoumarol involve Tyr 128 and Phe 232 that are present on the surface of the NQO1 catalytic pocket. Based on the comparison of NQO1 structure in complex with different NQO1 inhibitors and our previous analysis of NQO1 mutations that affect NQO1 interactions we propose that the specific conformation of Tyr 128 and Phe 232 is important for NQO1 interaction with p53 and other client proteins.