Conformation and position of membrane-bound amphotericin B deduced from NMR in SDS micelles.
Amphotericin B (AmB) is known to self-assemble to form an ion channel across lipid bilayer membranes. To gain insight into the conformation of AmB in lipidic environments, AmB in SDS micelles was subjected to high-resolution NMR and CD measurements, and the NMR-derived conformation thus obtained was refined by molecular mechanics calculations. These results indicate that AmB in SDS micelles is conformationally fixed particularly for the macrolide moiety. Paramagnetic relaxation experiments with the use of Mn2+ reveal that AmB is shallowly embedded in the micelle with the polyhydroxyl chain being close to the water interface and the side of polyene portion facing to the micelle interior. CD measurements demonstrate that AmB is in a monomeric form in SDS micelles. The structure of AmB in the micelles obtained in the present study may reproduce the initial stage of membrane interaction of AmB prior to the assembly formation in biomembranes.
Matsumori
Nobuaki
N
Department of Chemistry, Graduate School of Science, Osaka University, Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
Houdai
Toshihiro
T
Murata
Michio
M
D000666:Amphotericin B / Q000032:analysis / Q000737:chemistry*; D000935:Antifungal Agents / Q000032:analysis / Q000737:chemistry*; D002413:Cations, Divalent; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008345:Manganese / Q000737:chemistry; D008823:Micelles; D008968:Molecular Conformation; D011090:Polyenes / Q000737:chemistry; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*
D000935:Antifungal Agents; D002413:Cations, Divalent; D004337:Drug Carriers; D008051:Lipid Bilayers; D008823:Micelles; D011090:Polyenes; D012967:Sodium Dodecyl Sulfate; D008345:Manganese; D000666:Amphotericin B