Quinone reductase 2 is a catechol quinone reductase.
The functions of quinone reductase 2 have eluded researchers for decades even though a genetic polymorphism is associated with various neurological disorders. Employing enzymatic studies using adrenochrome as a substrate, we show that quinone reductase 2 is specific for the reduction of adrenochrome, whereas quinone reductase 1 shows no activity. We also solved the crystal structure of quinone reductase 2 in complexes with dopamine and adrenochrome, two compounds that are structurally related to catecholamine quinones. Detailed structural analyses delineate the mechanism of quinone reductase 2 specificity toward catechol quinones in comparison with quinone reductase 1; a side-chain rotational difference between quinone reductase 1 and quinone reductase 2 of a single residue, phenylalanine 106, determines the specificity of enzymatic activities. These results infer functional differences between two homologous enzymes and indicate that quinone reductase 2 could play important roles in the regulation of catecholamine oxidation processes that may be involved in the etiology of Parkinson disease.
Fu
Yue
Y
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.
Buryanovskyy
Leonid
L
Zhang
Zhongtao
Z
D000323:Adrenochrome / Q000737:chemistry*; D000818:Animals; D002395:Catecholamines / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000201:enzymology / Q000378:metabolism; D011110:Polymorphism, Genetic; D051381:Rats
D002395:Catecholamines; D000323:Adrenochrome; D016660:NAD(P)H Dehydrogenase (Quinone); D004298:Dopamine