Kieffer B, Dillmann B, Lefèvre J F, Goumon Y, Aunis D, Metz-Boutigue M H
CNRS, UPR 9003, Cancérogénèse et Mutagénèse Moléculaire et Structurale, 67400 Illkirch Graffenstaden, France.
J Biol Chem. 1998 Dec 11;273(50):33517-23. doi: 10.1074/jbc.273.50.33517.
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.
前脑啡肽原 - A已被描述可产生脑啡肽、阿片样肽和几种衍生肽，这些肽具有多种生物学效应，包括抗伤害感受和免疫增强作用。最近，我们从牛嗜铬颗粒中分离出一种新的抗菌肽，命名为脑溶素，它对应于PEAP209 - 237的双磷酸化形式（古蒙，Y.，斯特鲁布，J. M.，莫尼亚特，M.，努兰斯，G.，波特厄，L.，于贝尔，P.，范多塞尔拉尔，A.，奥尼斯，D.，和梅茨 - 布蒂格，M. H.（1996年）《欧洲生物化学杂志》235卷，516 - 525页）。在本文中，通过核磁共振研究了合成的PEAP209 - 237的三维溶液结构。这些研究表明，该肽在水中无结构，在三氟乙醇/水（1/1）中折叠成α - 螺旋结构。核磁共振数据揭示了PEAP209 - 237的两种可能的三维模型。在这两种模型中，脯氨酸残基Pro - 227在两个α - 螺旋片段（Ser - 215至Ser - 221和Glu - 228至Arg - 232）之间诱导出90度铰链，导致分子整体呈L形结构。PEAP209 - 237的负电荷以及两个α - 螺旋片段的低亲水性意味着有新的机制来解释脑溶素的抗菌活性。
