Solution conformation of the synthetic bovine proenkephalin-A(209-237) by H-1 NMR spectroscopy

Proenkephalin-A has been described to generate enkephalins, opoid peptides, and several derived peptides, which display various biological effects, in cluding antinociception and immunological enhancement. Recently, we have is olated from bovine chromaffin grannies a new antibacterial peptide, named e nkelytin, which corresponds to the bisphosphorylated form of PEAP(209-237) (Goumon, Y., Strub, J. M., Moniatte, M., Nullans, G., Poteur, L., Hubert, P ., Van Dorsselaer, A., Aunis, D., and Metz-Boutigue, M. H. (1996) Eur. J. B iochem. 235, 516-525). In this paper, the three-dimensional solution struct ure of synthetic PEAP(209-237) was investigated by NMR. These studies indic ate that this peptide, which is unstructured in water, folds into an cu-hel ical structure in trifluoroethanol/water (1/1). NMR data revealed two possi ble three-dimensional models of PEAP(209-237). In both models, the proline residue Pro-227 induces a 90 degrees hinge between two alpha-helical segmen ts (Ser-215 to Ser-221 and Glu-228 to Arg-232) leading to an overall L-shap ed structure for the molecule. The negative charge of PEAP(209-237) and the low amphipathy of the two alpha-helical segments imply new mechanisms to e xplain the antibacterial activity of enkelytin.