Crystal structure and a twisted beta-sheet conformation of the tripeptide L-leucyl-L-leucyl-L-leucine monohydrate trimethanol solvate: conformation analysis of tripeptides.

In order to test the helical preference of short oligo-L-leucines, we crystallized the tripeptide L-leucyl-L-leucyl-L-leucine (LLL) and carried out x-ray diffraction studies of it (L-leucyl-L-leucyl-Lleucine)2. 3CH3OH. H2O, (C39H84N6O12), crystallized in the monoclinic system, space group P2(1), cell parameters: a = 12.031(2), b = 15.578(3), c = 14.087(2) A, alpha = 90 degrees, beta = 97.29(1) degrees, gamma = 90 degrees, V = 2618.6 A3, MW = 829.1, Dc = 1.051 g cm-3, R index of 0.057 for 4213 reflections (lambda CuK alpha = 1.5418 A) > 2 sigma. LLL takes up the beta-sheet rather than a helical conformation in the crystalline state. The three methanol molecules and the water molecule that constitute the solvent of crystallization form a network of hydrogen bonds to the LLL molecules and to one another. It is rather remarkable that though A and L have stronger helical preferences than G, neither AAA nor LLL form the crystalline helix but GAL does, indicating that the helical preferences depend on the sequence context. The residue L2 in molecule A and the residues L1 and L3 of molecule B do not show the preferred conformation for forming helices. Further, very remarkably, LLL exhibits a unique supersecondary feature of the protein folding topology, namely the twisted beta-sheet, whereas most short peptides show only the classical beta-sheet conformation.(ABSTRACT TRUNCATED AT 250 WORDS)