AFM study of the interaction of cytochrome P450 2C9 with phospholipid bilayers

Matthew Nussio; Nicolas Voelcker; John Miners; Benjamin Lewis; Matthew Sykes; Joseph Shapter

doi:10.1016/j.chemphyslip.2009.11.003

AFM study of the interaction of cytochrome P450 2C9 with phospholipid bilayers

Matthew Nussio, Nicolas Voelcker, John Miners, Benjamin Lewis, Matthew Sykes, Joseph Shapter

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

Cytochromes P450 (CYP) are key enzymes involved in the metabolism of drugs and other lipophilic xenobiotics and endogenous compounds. In this study, atomic force microscopy was applied to characterise the association of CYP2C9 to dimyristoylphosphatidylcholine (DMPC) supported phospholipid bilayers. CYP2C9 was found to exclusively localise in the gel domains of partially melted DMPC bilayers. Despite lacking the N-terminus transmembrane spanning domain, the CYP2C9 protein appeared to partially embed into the membrane bilayer, as evidenced by an increase in melting temperature of surrounding phospholipids. Reversible binding of CYP2C9 via an engineered His tag to a phospholipid bilayer was facilitated using nickel-chelating lipids, presenting potential applications for biosensor technologies.

Original language	English
Pages (from-to)	182-189
Number of pages	8
Journal	Chemistry and Physics of Lipids
Volume	163
Issue number	2
DOIs	https://doi.org/10.1016/j.chemphyslip.2009.11.003
Publication status	Published - Feb 2010

Keywords

Atomic force microscopy (AFM)
Cytochrome P450
Membrane protein
Phospholipid bilayers

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10.1016/j.chemphyslip.2009.11.003

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title = "AFM study of the interaction of cytochrome P450 2C9 with phospholipid bilayers",

abstract = "Cytochromes P450 (CYP) are key enzymes involved in the metabolism of drugs and other lipophilic xenobiotics and endogenous compounds. In this study, atomic force microscopy was applied to characterise the association of CYP2C9 to dimyristoylphosphatidylcholine (DMPC) supported phospholipid bilayers. CYP2C9 was found to exclusively localise in the gel domains of partially melted DMPC bilayers. Despite lacking the N-terminus transmembrane spanning domain, the CYP2C9 protein appeared to partially embed into the membrane bilayer, as evidenced by an increase in melting temperature of surrounding phospholipids. Reversible binding of CYP2C9 via an engineered His tag to a phospholipid bilayer was facilitated using nickel-chelating lipids, presenting potential applications for biosensor technologies.",

keywords = "Atomic force microscopy (AFM), Cytochrome P450, Membrane protein, Phospholipid bilayers",

author = "Matthew Nussio and Nicolas Voelcker and John Miners and Benjamin Lewis and Matthew Sykes and Joseph Shapter",

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T1 - AFM study of the interaction of cytochrome P450 2C9 with phospholipid bilayers

AU - Nussio, Matthew

AU - Voelcker, Nicolas

AU - Miners, John

AU - Lewis, Benjamin

AU - Sykes, Matthew

AU - Shapter, Joseph

PY - 2010/2

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AB - Cytochromes P450 (CYP) are key enzymes involved in the metabolism of drugs and other lipophilic xenobiotics and endogenous compounds. In this study, atomic force microscopy was applied to characterise the association of CYP2C9 to dimyristoylphosphatidylcholine (DMPC) supported phospholipid bilayers. CYP2C9 was found to exclusively localise in the gel domains of partially melted DMPC bilayers. Despite lacking the N-terminus transmembrane spanning domain, the CYP2C9 protein appeared to partially embed into the membrane bilayer, as evidenced by an increase in melting temperature of surrounding phospholipids. Reversible binding of CYP2C9 via an engineered His tag to a phospholipid bilayer was facilitated using nickel-chelating lipids, presenting potential applications for biosensor technologies.

KW - Atomic force microscopy (AFM)

KW - Cytochrome P450

KW - Membrane protein

KW - Phospholipid bilayers

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DO - 10.1016/j.chemphyslip.2009.11.003

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EP - 189

JO - Chemistry and Physics of Lipids

JF - Chemistry and Physics of Lipids

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AFM study of the interaction of cytochrome P450 2C9 with phospholipid bilayers

Abstract

Keywords

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