CYP2A6*6, a Novel Polymorphism in Cytochrome P450 2A6, Has a Single Amino Acid Substitution (R128Q) that Inactivates Enzymatic Activity

83Citations
Citations of this article
24Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

By using the polymerase chain reaction technique combined with restriction enzyme fragment length polymorphism (PCR-RFLP), a novel polymorphism of CYP2A6, CYP2A6*6, was detected in 0.4% of the Japanese population. To study the enzymatic properties of the CYP2A6.6 protein with a single amino acid substitution of arginine 128 to glutamine, both this isozyme and the CYP2A6.1 protein (wild-type) were produced in insect cells using a baculovirus system. Coumarin 7-hydroxylation, which reflects CYP2A6 activity, was significantly reduced (one-eighth of normal) in cell lysate from CYP2A6*6-transfected Sf9 cells compared with that lysate from CYP2A6*1-transfected cells. To clarify the mechanism of inactivation of the CYP2A6.6 enzyme, the heme content and reduced CO difference spectrum were examined. Although CYP2A6.6 retained about one-half the heme content of CYP2A6.1, the reduced CO-bound Soret peak was completely lost. These results suggest that the inactivation of CYP2A6.6 is mainly due to disordering of the holoprotein structure rather than a failure of heme incorporation.

Cite

CITATION STYLE

APA

Kitagawa, K., Kunugita, N., Kitagawa, M., & Kawamoto, T. (2001). CYP2A6*6, a Novel Polymorphism in Cytochrome P450 2A6, Has a Single Amino Acid Substitution (R128Q) that Inactivates Enzymatic Activity. Journal of Biological Chemistry, 276(21), 17830–17835. https://doi.org/10.1074/jbc.M009432200

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free