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.
authors.affiliation: School of Chemistry, Physics and Earth Sciences, Flinders University, Sturt Road, Bedford Park, Adelaide, SA 5001, Australia.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Nussio
authors.forename: Nicolas H
authors.initials: NH
authors.lastname: Voelcker
authors.forename: John O
authors.initials: JO
authors.lastname: Miners
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Lewis
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sykes
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Shapter
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D009532:Nickel / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D044366:Transition Temperature
chemical_list: D008051:Lipid Bilayers; D011994:Recombinant Proteins; D009532:Nickel; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D004134:Dimyristoylphosphatidylcholine