Solution conformation of the synthetic bovine proenkephalin-A209-237 by 1H NMR spectroscopy.
Proenkephalin-A has been described to generate enkephalins, opoid peptides, and several derived peptides, which display various biological effects, including antinociception and immunological enhancement. Recently, we have isolated from bovine chromaffin granules a new antibacterial peptide, named enkelytin, which corresponds to the bisphosphorylated form of PEAP209-237 (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. Biochem. 235, 516-525). In this paper, the three-dimensional solution structure of synthetic PEAP209-237 was investigated by NMR. These studies indicate that this peptide, which is unstructured in water, folds into an alpha-helical structure in trifluoroethanol/water (1/1). NMR data revealed two possible three-dimensional models of PEAP209-237. In both models, the proline residue Pro-227 induces a 90 degrees hinge between two alpha-helical segments (Ser-215 to Ser-221 and Glu-228 to Arg-232) leading to an overall L-shaped structure for the molecule. The negative charge of PEAP209-237 and the low amphipathy of the two alpha-helical segments imply new mechanisms to explain the antibacterial activity of enkelytin.
Kieffer
B
B
CNRS, UPR 9003, Cancérogénèse et Mutagénèse Moléculaire et Structurale, 67400 Illkirch Graffenstaden, France.
Dillmann
B
B
Lefèvre
J F
JF
Goumon
Y
Y
Aunis
D
D
Metz-Boutigue
M H
MH
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D004745:Enkephalins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry*; D011522:Protons; D012996:Solutions; D055672:Static Electricity
D004745:Enkephalins; D011498:Protein Precursors; D011522:Protons; D012996:Solutions; C029992:proenkephalin