Role of modified glutamic acid in the helical structure of conantokin-T.

Circular dichroism (CD) and 2-dimensional NMR were used to study the solution conformation of conantokin-T (Con-T), a small peptide toxin found in the venom of fish-hunting cone snails, and its Glu-substituted analog. Con-T lacks disulfide bonds but contains many gamma-carboxyglutamic acids (Gla), a post-translationally modified residue. Our results show that Con-T adopts an alpha-helical conformation in aqueous solution even in the absence of calcium. Glu replacements diminish both helicity and function of Con-T. The helical content of Con-T is higher than most natural helical peptides of this length in aqueous solution. The sequence of this small toxin incorporates several known elements that stabilize alpha-helical structure in peptides. Gla residues form several salt bridges that stabilize helical conformation of Con-T.