C—H⋯O hydrogen bond involving proline residues in α-helices

Abstract

Despite proline being assumed to be a helix-breaker, a large number of α-helices are found to contain Pro in globular as well as membrane proteins. Proline has no free NH group and therefore cannot form the conventional intra-helical NH⋯O = C hydrogen bond. An analysis of known protein structures has shown that the Cδ protons are involved in C—H⋯O hydrogen bonds, usually two, with the carbonyl groups in the preceding turn of the helix (four and three residues away). These interactions satisfy the hydrogen bond forming potential of the carbonyl groups, which would otherwise, in the case of membrane-bound helices, be unfavorably exposed to hydrophobic surroundings. Depending on the type (based on the location of the carbonyl group, usually three, four or five residues preceding Pro) of C—H⋯O interactions, the kink in the helix may be of different magnitude. The puckering (UP or DOWN) of the pyrrolidine ring of Pro residues is controlled by the type of the C—H⋯O bond present, and the form that provides a better hydrogen bond geometry is preferred.