Dissociation Constants of Cytochrome P450 2C9/Cytochrome P450 Reductase Complexes in a Lipid Bilayer Membrane Depend on NADPH: A Single-Protein Tracking Study
| Autor: | Carlo Barnaba, James A. Brozik, Evan Taylor |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cytochrome Stereochemistry Lipid Bilayers Oxidative phosphorylation Biochemistry Catalysis Diffusion 03 medical and health sciences Colloid and Surface Chemistry Humans Lipid bilayer Cytochrome P-450 CYP2C9 NADPH-Ferrihemoprotein Reductase biology Chemistry Cytochrome b Endoplasmic reticulum Cytochrome c Cytochrome P450 reductase General Chemistry Single Molecule Imaging Dissociation constant 030104 developmental biology Multiprotein Complexes biology.protein Thermodynamics Oxidation-Reduction NADP Protein Binding |
| Zdroj: | Journal of the American Chemical Society. 139:17923-17934 |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | Cytochrome P450-reductase (CPR) is a versatile NADPH-dependent electron donor located in the cytoplasmic side of the endoplasmic reticulum. It is an electron transferase that is able to deliver electrons to a variety of membrane-bound oxidative partners, including the drug-metabolizing enzymes of the cytochrome P450s (P450). CPR is also stoichiometrically limited compared to its oxidative counterparts, and hypotheses have arisen about possible models that can overcome the stoichiometric imbalance, including quaternary organization of P450 and diffusion-limited models. Described here are results from a single-protein tracking study of fluorescently labeled CPR and cytochrome P450 2C9 (CYP2C9) molecules in which stochastic analysis was used to determine the dissociation constants of CPR/CYP2C9 complexes in a lipid bilayer membrane for the first time. Single-protein trajectories demonstrate the transient nature of these CPR–CYP2C9 interactions, and the measured Kd values are highly dependent on the redox sta... |
| Databáze: | OpenAIRE |
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