THE THREE DIMENSIONAL STRUCTURE OF MOUSE NAD(P)H: QUINONE REDUCTASE EXPRESSED IN E. COLI. Mario A. Bianchet¹, Margarita Faig¹, Shiuan Chen², Paul Talalay³ and L. Mario Amzel¹, Dept. of Biophysics & Biophysical Chemistry, ¹Johns Hopkins School of Medicine, Baltimore, MD, 21205, Division of Immunology, ²Beckman Research Institute of the City of Hope, Duarte, CA 91010, ³Dept. of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205^.

Quinone Reductase (EC.1.6.99.2), also called DT:Diaphorase, is a flavoprotein that catalyses the two electron reduction of quinones and quinoinimines using NAD(P)H as electron donors. QR was shown to be an important chemoprotector agent against the carcinogenic effect of quinones. The 3-D structure of mouse Quinone Reductase (QR) in the presence of FAD was determined in two crystal forms by X-ray diffraction methods. Although QR activity is different for different species, the activities of human and mouse enzymes are very similar vis- a-vis the rat enzyme. Comparison of the mouse structure with the available rat model (Li et al. 1995) can provide a rationale for the observed differences. One aminoacid substitution in the FAD binding pocket has a marked effect in the positioning of FAD.

Li, R., Bianchet, M.A., Talalay, P. and Amzel, L.M. (1995) Proc. Natl. Acad. Sci. USA 92. 8846 - 8850