Quinone Reductase 2 Is a Catechol Quinone Reductase
- NYMEDCO
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.
- Research Organization:
- Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1006788
- Journal Information:
- J. Biol. Chem., Journal Name: J. Biol. Chem. Journal Issue: (35) ; 08, 2008 Vol. 283; ISSN 0021-9258; ISSN JBCHA3
- Country of Publication:
- United States
- Language:
- ENGLISH
Similar Records
X-ray structural studies of quinone reductase 2 nanomolar range inhibitors
Design, Synthesis, and Biological Evaluation of Potent Quinoline and Pyrroloquinoline Ammosamide Analogues as Inhibitors of Quinone Reductase 2