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Report No.

Crystal structure of human drug metabolizing enzyme CYP2C9 in complex with losartan determined by X-ray crystallography

Adachi, Motoyasu; Maekawa, Keiko*; Matsuzawa, Yumiko*; Saito, Yoshiro*; Kuroki, Ryota

CYP2C9 belongs to cytochrome P450 and play an important role as human drug metabolizing enzyme. In this study, to elucidate molecular mechanism in drug metabolizing reaction by wild-type CYP2C9 and its SNP mutant *30, X-ray structures of their CYP2C9 molecules complexed with the drug were determined. CYP2C9 was truncated at N-terminal, expressed in E. coli, and homogeneously purified for crystallization. CYP2C9 Losartan complex was crystallized by co-crystallization. As a result of experiments using synchrotron radiation, diffraction data were obtained at 2.1${AA}$ resolution. The electron density maps of bound Losartan were observed in the both complexes.



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