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J Biol Chem. 2017 Dec 22;292(51):20818-20833. doi: 10.1074/jbc.RA117.000220. Epub 2017 Oct 27.

Structural and functional effects of cytochrome b5 interactions with human cytochrome P450 enzymes.

Author information

1
From the Biophysics Program and.
2
From the Biophysics Program and scottee@umich.edu.
3
the Departments of Medicinal Chemistry and Pharmacology, University of Michigan, Ann Arbor, Michigan 48109.

Abstract

The small heme-containing protein cytochrome b5 can facilitate, inhibit, or have no effect on cytochrome P450 catalysis, often in a P450-dependent and substrate-dependent manner that is not well understood. Herein, solution NMR was used to identify b5 residues interacting with different human drug-metabolizing P450 enzymes. NMR results revealed that P450 enzymes bound to either b5 α4-5 (CYP2A6 and CYP2E1) or this region and α2-3 (CYP2D6 and CYP3A4) and suggested variation in the affinity for b5 Mutations of key b5 residues suggest not only that different b5 surfaces are responsible for binding different P450 enzymes, but that these different complexes are relevant to the observed effects on P450 catalysis.

KEYWORDS:

cytochrome; cytochrome P450; membrane protein; nuclear magnetic resonance (NMR); protein-protein interaction

PMID:
29079577
PMCID:
PMC5743060
[Available on 2018-12-22]
DOI:
10.1074/jbc.RA117.000220

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