The reverse turn as a template for metal coordination

Abstract

The structural consequence of zinc binding to three octapeptides is examined. The experimental results indicate that placement of a constrained reverse turn motif in the core of the peptide nucleates the peptide secondary structure to facilitate metal coordination to ligands within the remainder of the sequence. These studies demonstrate that secondary structure in a polypeptide framework may be enhanced by a combination of β-turn nucleation and metal coordination. The structural consequences of metal cation binding to three, Ac-Glu-Gly-Val-Pro-DSer-His-Thr-His-NH 2 ( 1), Ac-His-Gly-Val-Pro-DSer-His-Thr-His-NH 2 ( 2), and Ac-His-Gly-Val-Gly-Gly-His-Thr-His-NH 2 ( 3) are examined by 1H NMR and CD. Evidence is provided to indicate that the structural preorganization provided by the constrained type II β-1 turn, in the core of the sequence, is an important determinant for effective metal complexation. Spectroscopic changes resultant on metal binding suggest the presence of a β-hairpin structure. In the absence of such a constraint, metal complexation is ineffective and defined structural changes are not observed.