A. Prewett, Ben Riegsecker, Ethan D Angle
Apr 1, 2020
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Journal
The FASEB Journal
Abstract
The Cytochromes P450 2B6 (CYP2B6) and 2A6 (CYP2A6) participate in the metabolism of the anti‐HIV drug Efavirenz (EFV). CYP2B6 monohydroxylation of EFV results in the formation of 8‐hydroxyefavirenz (8‐OHEFV) whereas CYP2A6 monohydroxylation of EFV forms 7‐hydroxyefavirenz (7‐OHEFV). To date, little is known about the structural characteristics of these enzymes that lead to differential EFV metabolite formation. In order to better understand such characteristics, we sought to mutate CYP2B6 towards CYP2A6 in hopes of uncovering amino acids critical for the formation of 8‐OHEFV. Specifically, we decided to focus on two phenylalanine residues in the CYP2A6 active site that are valines at the analogous positions in CYP2B6.