Solution NMR structures of the polyene macrolide antibiotic filipin III.
The solution structure of filipin III, an antifungal polyene macrolide biosynthesized by Streptomyces filipinensis and widely used for the detection and the quantitation of cholesterol in biomembranes, has been calculated with a set of geometrical restraints derived from 1H NMR in DMSO-d(6) at 25 degrees C. Filipin III appears as a rod-shaped molecule of 18 A length. Its amphiphilic structure is made of an all-syn 1,3-polyol motif, stabilized by intramolecular hydrogen bonds on one side, and a conjugated pentaene moiety on the other side of the molecule. The overall shape is comparable to cholesterol, and the molecular structure of filipin III affords a first molecular basis to the comprehensive understanding of the interactions possible in the filipin III-cholesterol complex which is still unknown at the atomic resolution.
Laboratoire de RMN Biomoléculaire associé au CNRS, Université Claude Bernard-Lyon 1 et Ecole Supérieure de Chimie Physique et Electronique de Lyon, Bâtiment 308G, F-69622, Villeurbanne, France.
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D000935:Antifungal Agents / Q000737:chemistry* / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D005372:Filipin / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D012996:Solutions; D013302:Streptomyces / Q000737:chemistry*
D000935:Antifungal Agents; D012996:Solutions; D005372:Filipin; D002784:Cholesterol