title: Double-stranded helical twisted beta-sheet channels in crystals of gramicidin S grown in the presence of trifluoroacetic and hydrochloric acids.
abstract: Gramicidin S is a nonribosomally synthesized cyclic decapeptide antibiotic with twofold symmetry (Val-Orn-Leu-D-Phe-Pro)(2); a natural source is Bacillus brevis. Gramicidin S is active against Gram-positive and some Gram-negative bacteria. However, its haemolytic toxicity in humans limits its use as an antibiotic to certain topical applications. Synthetically obtained gramicidin S was crystallized from a solution containing water, methanol, trifluoroacetic acid and hydrochloric acid. The structure was solved and refined at 0.95 A resolution. The asymmetric unit contains 1.5 molecules of gramicidin S, two trifluoroacetic acid molecules and ten water molecules located and refined in 14 positions. One gramicidin S molecule has an exact twofold-symmetrical conformation; the other deviates from the molecular twofold symmetry. The cyclic peptide adopts an antiparallel beta-sheet secondary structure with two type II' beta-turns. These turns have the residues D-Phe and Pro at positions i + 1 and i + 2, respectively. In the crystals, the gramicidin S molecules line up into double-stranded helical channels that differ from those observed previously. The implications of the supramolecular structure for several models of gramicidin S conformation and assembly in the membrane are discussed.
authors.affiliation: Unidad de Difracción de Rayos X (RIAIDT), Laboratorio Integral de Dinámica y Estructura de Biomoléculas José R. Carracido, Edificio CACTUS, Campus Sur, Universidad de Santiago de Compostela, E-15782 Santiago de Compostela, Spain. allamas@usc.es
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Llamas-Saiz
authors.forename: Gijsbert M
authors.initials: GM
authors.lastname: Grotenbreg
authors.forename: Mark
authors.initials: M
authors.lastname: Overhand
authors.forename: Mark J
authors.initials: MJ
authors.lastname: van Raaij
mesh_terms: D018360:Crystallography, X-Ray; D006096:Gramicidin / Q000737:chemistry*; D006851:Hydrochloric Acid / Q000737:chemistry*; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D014269:Trifluoroacetic Acid / Q000737:chemistry*
chemical_list: D006096:Gramicidin; D014269:Trifluoroacetic Acid; D006851:Hydrochloric Acid