title: What Is the Preferred Conformation of Phosphatidylserine-Copper(II) Complexes? A Combined Theoretical and Experimental Investigation.
abstract: Phosphatidylserine (PS) has previously been found to bind Cu2+in a ratio of 1 Cu2+ion per 2 PS lipids to form a complex with an apparent dissociation constant that can be as low as picomolar. While the affinity of Cu2+for lipid membranes containing PS lipids has been well characterized, the structural details of the Cu-PS2complex have not yet been reported. Coordinating to one amine and one carboxylate moiety on two separate PS lipids, the Cu-PS2complex is unique among ion-lipid complexes in its ability to adopt both cis and trans conformations. Herein, we determine which stereoisomer of the Cu-PS2complex is favored in lipid bilayers using density functional theory calculations and electron paramagnetic resonance experiments. It was determined that a conformation in which the nitrogen centers are cis to each other is the preferred binding geometry. This is in contrast to the complex formed when two glycine molecules bind to Cu2+in bulk solution, where the cis and trans isomers exist in equilibrium, indicating that the lipid environment has a significant steric effect on the Cu2+binding conformation. These findings are relevant for understanding lipid oxidation caused by Cu2+binding to lipid membrane surfaces and will help us understand how ion binding to lipid membranes can affect their physical properties.
authors.affiliation: Department of Chemistry, Chemical Theory Center, and Minnesota Supercomputing Institute, University of Minnesota , 207 Pleasant Street SE, Minneapolis, Minnesota 55455-0431, United States.
authors.forename: Kari
authors.initials: K
authors.lastname: Kusler
authors.affiliation: Department of Chemistry, Chemical Theory Center, and Minnesota Supercomputing Institute, University of Minnesota , 207 Pleasant Street SE, Minneapolis, Minnesota 55455-0431, United States.
authors.forename: Samuel O
authors.initials: SO
authors.lastname: Odoh
authors.affiliation: Department of Chemistry, The Pennsylvania State University , 104 Chemistry Building, University Park, Pennsylvania 16802, United States.
authors.forename: Alexey
authors.initials: A
authors.lastname: Silakov
authors.affiliation: Department of Chemistry, The Pennsylvania State University , 104 Chemistry Building, University Park, Pennsylvania 16802, United States.
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Poyton
authors.affiliation: Department of Chemistry, The Pennsylvania State University , 104 Chemistry Building, University Park, Pennsylvania 16802, United States.
authors.forename: Saranya
authors.initials: S
authors.lastname: Pullanchery
authors.affiliation: Department of Chemistry, The Pennsylvania State University , 104 Chemistry Building, University Park, Pennsylvania 16802, United States.
authors.forename: Paul S
authors.identifier: 0000-0002-8524-0438
authors.initials: PS
authors.lastname: Cremer
authors.affiliation: Department of Chemistry, Chemical Theory Center, and Minnesota Supercomputing Institute, University of Minnesota , 207 Pleasant Street SE, Minneapolis, Minnesota 55455-0431, United States.
authors.forename: Laura
authors.identifier: 0000-0001-5227-1396
authors.initials: L
authors.lastname: Gagliardi
mesh_terms: D002413:Cations, Divalent; D003300:Copper / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry*; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry*; D010718:Phosphatidylserines / Q000737:chemistry*; D011789:Quantum Theory; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D002413:Cations, Divalent; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; C050294:1-palmitoyl-2-oleoylglycero-3-phosphoserine; D003300:Copper; C028694:1-palmitoyl-2-oleoylphosphatidylcholine