Membrane topology and search for potential redox partners of colon cancer-specific cytochrome P450 2W1

FEBS Letters
Jia GuoMagnus Ingelman-Sundberg

Abstract

Cytochrome P450 2W1 (CYP2W1) is a colon tumor-specific enzyme, suggested as a potential target for cancer therapy. In contrast to other endoplasmic reticulum P450s, we found completely inverted ER membrane topology of CYP2W1 using different approaches (redox sensitive luciferase assay and protease protection assay) and demonstrated that canonical CYP reductants, cytochrome P450 reductase, and cytochrome b5 cannot serve as electron donors for CYP2W1. Moreover, the reduced catalytic activity of the Asn177 mutant that is modified by glycan moieties in the wild-type enzyme indicates a functional relevance of CYP2W1 glycosylation.

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Citations

Jun 4, 2016·Drug Metabolism Reviews·Jia GuoMagnus Ingelman-Sundberg
Oct 4, 2016·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Yan Pan, Eng Chin Ong
Oct 6, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Aaron G BartEmily E Scott

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