Structure-function studies of DT-diaphorase (NQO1) and NRH: quinone oxidoreductase (NQO2).
DT-diaphorase, also referred to as NQO1 or NAD(P)H: quinone acceptor oxidoreductase, is a flavoprotein that catalyzes the two-electron reduction of quinones and quinonoid compounds to hydroquinones, using either NADH or NADPH as the electron donor. NRH (dihydronicotinamide riboside): quinone oxidoreductase, also referred to as NQO2, has a high nucleotide sequence identity to DT-diaphorase and is considered to be an isozyme of DT-diaphorase. These enzymes transfer two electrons to a quinone, resulting in the formation of a hydroquinone product without the accumulation of a dissociated semiquinone. Steady and rapid-reaction kinetic experiments have been performed to determine the reaction mechanism of DT-diaphorase. Furthermore, chimeric and site-directed mutagenesis experiments have been performed to determine the molecular basis of the catalytic differences between the two isozymes and to identify the critical amino acid residues that interact with various inhibitors of the enzymes. In addition, functional studies of a natural occurring mutant Pro-187 to Ser (P187S) have been carried out. Results obtained from these investigations are summarized and discussed.
Chen
S
S
Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA. schen@coh.org
Wu
K
K
Knox
R
R
D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D016660:NAD(P)H Dehydrogenase (Quinone)