Trends Biochem Sci. 2005 Jan;30(1):5-7.

Structures of cytochrome P450 3A4.

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Department of Medicinal Chemistry, University of Kansas, Lawrence, KS 66045-7582, USA. eescott@ku.edu

Abstract

Cytochrome P450 3A4 (CYP3A4) catalyzes the initial step in the clearance of many pharmaceuticals and foreign chemicals. The structurally diverse nature of CYP3A4 substrates complicates rational prediction of their metabolism and identification of potential drug interactions. The first molecular structures of human CYP3A4 were recently determined, revealing an active site of sufficient size and topography to accommodate either large ligands or multiple smaller ligands, as suggested by the heterotropic and homotropic cooperativity of the enzyme.

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