About this Biochemistry, Genetics and Molecular Biology article

Tight-binding inhibition by α-naphthoflavone of human cytochrome P450 1A2 by Uhn Soo Cho; Eun Young Park; Mi Sook Dong; Bum Seok Park; Keehyuk Kim; Kyung Hyun Kim is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

Human cytochrome P450 (P450) enzymes exhibit remarkable diversity in their substrate specificities, participating in oxidation reactions of a wide range of xenobiotic drugs. Previously, we reported that alpha-naphthoflavone (ANF) is bound to the recombinant P450 1A2 tightly and stabilizes an overall enzyme conformation. The present study is designed to determine the type of P450 1A2 inhibition exerted by ANF, using two different substrates of P450 1A2, 7-ethoxycoumarin (EOC) and 7-ethoxyresorufin (EOR). ANF is generally known as a competitive inhibitor of the enzyme. However, in our tight-binding enzyme kinetics study, ANF acts as noncompetitive inhibitor in 7-ethoxycoumarin O-deethylation (ECOD) (K(i)=55.0 nM), but as competitive inhibitor in 7-ethoxyresorufin O-deethylation (EROD) (K(i)=1.4 nM). Based on homology modeling studies, ANF is positioned to bind to a hydrophobic cavity next to the active site where it may cause a direct effect on substrate binding. It is agreed with the predicted binding site of ANF in P450 3A4, in which ANF is rather known as a stimulating modulator. Our results suggest that ANF binds near the active site of P450 1A2 and exhibits differential inhibiti

Author

Uhn Soo Cho; Eun Young Park; Mi Sook Dong; Bum Seok Park; Keehyuk Kim; Kyung Hyun Kim

Publisher

Elsevier Science; Elsevier ; Elsevier BV (ISSN 1570-9639)

Published

2003

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)