Antiparallel pleated beta-sheets observed in crystal structures of N,N-bis(trichloroacetyl) and N,N-bis(m-bromobenzoyl) gramicidin S.
Despite intensive efforts, the structures of gramicidin S (GS) [cyclo(-Val-Orn-Leu-d-Phe-Pro-)(2)] and its analogues have not been elucidated by the X-ray diffraction method, except for the GS-urea complex (Hull et al., Nature 275, 206-207, 1978; Tishchenko et al., Acta Cryst. D53, 151-159, 1997). We focused on the acetylation of GS to obtain suitable crystals for X-ray diffraction. The amino groups of Orn residues were capped with trichloroacetic and m-bromobenzoic acids. Both trichloroacetyl and m-bromobenzoyl GSs (TcGS and BzGS, respectively) are hydrophobic and their properties are similar to those of acetyl-GS (AcGS). Although it is well known that AcGS yields hexagonal crystals, TcGS and BzGS yield monoclinic and orthorhombic crystals in aqueous dimethylformamide solution, respectively. Their cell volumes were approximately one-fourth or one-eighth of the hexagonal cell volume. The crystal structures of TcGS and BzGS were determined as the first examples of acetylated GS analogues: TcGS, C(64)H(90)N(12)O(12)Cl(6). 3(C(3)H(7)NO), M(r) = 1651.47, monoclinic, P2(1), a = 15.4366(6) A, b = 18.5312(4) A, c = 16.4774(6) A, beta = 14.160(2) degrees, V = 4300.6(2) A(3), Z = 2; and BzGS, C(64)H(98)N(12)O(12)Br(2). 1.54(H(2)O), M(r) = 1535.21, orthorhombic, P2(1)2(1)2(1), a = 16.748(10) A, b = 18.834(5) A, c = 28.558(10) A, V = 9008(7) A(3), Z = 4. Both these peptide molecules formed an antiparallel pleated beta-sheet, and pseudo twofold symmetries existed in the repeated sequence. beta-Turns formed at the fragments of d-Phe-Pro were classified into type II' based on their characteristics. The peptide conformations of TcGS and BzGS were similar to each other, and these structural features agreed with those of structures proposed by the previous studies.
Doi
M
M
Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, 569-1094, Japan. doit@oysun01.oups.ac.jp
Fujita
S
S
Katsuya
Y
Y
Sasaki
M
M
Taniguchi
T
T
Hasegawa
H
H
D001970:Bromobenzoates / Q000737:chemistry*; D002234:Carbodiimides / Q000737:chemistry; D003460:Crystallization; D006096:Gramicidin / Q000031:analogs & derivatives* / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D017433:Protein Structure, Secondary / Q000502:physiology; D017434:Protein Structure, Tertiary; D014238:Trichloroacetic Acid / Q000737:chemistry*; D014961:X-Ray Diffraction
D001970:Bromobenzoates; D002234:Carbodiimides; D006096:Gramicidin; D014238:Trichloroacetic Acid