RESUMEN
The structure of membrane-active antibiotic cyclodecapeptide gramicidin S in the crystals of its complex with urea, C(60)H(92)N(12)0(10).0.(5)[(NH(2))(2)CO].7.94H(2)0, has been investigated with three-dimensional X-ray data by the automatic sequential approximation method. The crystals are trigonal, space group P3(1)21, a = 25.80(3), c= 21.49 (2) A, M(r) = 7968, calculated density = 1.088 mg m(-3), Z = 1. Conventional R factor: R1 = 0.0943, wR2 = 0.2478 [I> 2sigma(I)]. The molecule possesses an antiparallel twisted beta-structure, with turns involving the Phe-Pro peptides. The Orn side chains extend on one side of the sheet, while the non-polar Val and Leu side chains are located on the other face. One of the Orn residues (namely Orn2) is linked by an intermolecular hydrogen bond to the O atom of Phe4 residue, the other is free. The side chains of the Phe residues have trans orientation (chi(1) approximately 180 degrees ) and those of the Val, Orn, Leu residues, except those of Orn2, have the preferential gauche orientation with the chi(1) angle close to 60. Two side chains show statistical disorder and conformation of the Pro residues is C(s)-C(beta)-exo. There is half a urea molecule and also 7.94 water molecules distributed on 13 positions for each antibiotic molecule. A partially occupied and poorly ordered alcohol molecule had been identified. The gramicidin S molecules are arranged around the 3(1) axis in the form of a left-handed double spiral forming suggestive channels. The outer hydrophobic surface of the spiral is made of uncharged side radicals while the inside surface consists of the main-chain atoms, mainly O and N, and of ornithine side chains with N atoms at the ends. By changing the Orn side-chain conformation, the inner diameter of the channels may change from 3.4 to 6.3 A. Thus, ions and particles of rather large size may pass through the channel. The possibility of the creation of the gramicidin S channels in mitochondrial membranes has been noted by some biochemists. The channel complexes are close-packed in a hexagonal arrangement in the crystal. The CI(-) ions, present in abundance in the mother solution, are not found ordered in the crystals, which may indicate the absence of the charges in the terminal N atoms of the Orn residues.
