title: Helix-forming tendencies of amino acids depend on their sequence contexts: tripeptides AFG and FAG show incipient beta-bulge formation in their crystal structures.
abstract: Many of the theoretical methods used for predicting the occurrence of alpha-helices in peptides are based on the helical preferences of amino acid monomer residues. In order to check whether the helix-forming tendencies are based on helical preferences of monomers only or also on their sequence contexts, we synthesized permuted sequences of the tripeptides GAF, GAV, and GAL that formed crystalline helices with near alpha-helical conformation. The tripeptides AFG and FAG formed good crystals. The x-ray crystallographic studies of AFG and FAG showed that though they contain the same amino acids as GAF but in different sequences, they do not assume a helical conformation in the solid state. On the other hand, AFG and FAG, which contain the same amino acids but in a different sequence, exhibit nearly the same backbone torsion angles corresponding to an incipient formation of a beta-bulge, and exhibit nearly identical unit cells and crystal structures. Based on these results, it appears that the helix-forming tendencies of amino acids depend on the sequence context in which it occurs in a polypeptide. The synthetic peptides AFG (L-Ala-L-Phe-Gly) and FAG (L-Phe-L-Ala-Gly), C14H19N3O4, crystallize in the orthorhombic space group P2(1)2(1)2(1), with a = 5.232(1), b = 14.622(2), c = 19.157(3) A, Dx = 1.329 g cm-3, Z = 4, R = 0.041 for 549 reflections for AFG, and with a = 5.488(2), b = 14.189(1), c = 18.562(1) A, Dx = 1.348 g cm-3, Z = 4, R = 0.038 for 919 reflections for FAG. Unlike the other tripeptides GAF, GGV, GAL, and GAI, the crystals of AFG and FAG do not contain water molecule, and the molecules of AFG aor FAG do not show the helical conformation. The torsion angles at the backbone of the peptide are psi 1 = 144.5(5) degrees; phi 2, psi 2 = -98.1(6) degrees, -65.2(6) degrees; phi 3, psi 13, psi 31 = 154.1(6) degrees, -173.6(6) degrees, 6.9(8) degrees for AFG; and psi 1 = 162.6(3) degrees; phi 2, psi 2 = -96.7(4) degrees, -46.3(4) degrees; phi 3, psi 13, psi 31 = 150.1(3) degrees, -168.7(3) degrees, 12.2(5) degrees for FAG. The conformation angles (phi, psi) for residues 2 and 3 for both AFG and FAG show incipient formation of an beta-bulge.
authors.affiliation: Center for Crystallographic Research, Roswell Park Cancer Institute, Buffalo, New York 14263.
authors.forename: R
authors.initials: R
authors.lastname: Parthasarathy
authors.forename: K
authors.initials: K
authors.lastname: Go
authors.forename: S
authors.initials: S
authors.lastname: Chaturvedi
mesh_terms: D000595:Amino Acid Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D009842:Oligopeptides