The C-terminal bisphosphorylated proenkephalin-A-(209-237)-peptide from adrenal medullary chromaffin granules possesses antibacterial activity
The C-terminal bisphosphorylated proenkephalin-A-(209-237)-peptide from adrenal medullary chromaffin granules possesses antibacterial activity
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DOI：
10.1111/j.1432-1033.1996.t01-1-00516.x
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发表时间：
1996-02-01
期刊：
影响因子：
--
通讯作者：
MetzBoutigue, MH
中科院分区：
文献类型：
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作者：
Goumon, Y;Strub, JM;MetzBoutigue, MH
嗜铬颗粒是研究脑啡肽原A和嗜铬颗粒蛋白加工的理想模型。最近，我们报道了一项研究，涉及嗜铬粒蛋白B/分泌粒蛋白I的加工和C-末端嗜铬粒蛋白B衍生肽614-626的出现，其显示出具有抗菌活性[Stru B，J.M.，Garcia-Sablone，P.，Looning，K.，陶珀诺湖休伯特，P.，货车Dorsselaer，A.，Aunis，D. & Metz-Boutigue，M. H.（1995）Eur J.Biochem.229，356-368]。我们还观察到，这种新的抗菌活性存在于嗜铬颗粒与其他内源性蛋白质衍生的片段尚未被表征。本研究报告了一种具有抗菌活性的肽的分离和表征，该肽对应于前脑啡肽原-A的C-末端209-237序列。使用微测序和基质辅助激光解吸飞行时间质谱（MALD-TOF MS）的详细研究使我们能够将这种名为enkelytin（FAEPLPSEEEGE-SYSKEVPEMEKRYGGFM）的肽的抗菌活性与翻译后修饰相关联。内源性双磷酸化的原脑啡肽-A-（209-237）在0.2-0.4 μ M范围内对藤黄微球菌和巨大芽孢杆菌有杀灭细菌的活性，但在类似条件下对大肠杆菌无活性。Enkelytin与地西泮结合抑制剂的抗菌C-末端结构域具有序列和结构相似性。根据这种相似性，预测的二级结构提出enkelytin和讨论有关其生物活性。
The chromaffin granules have been shown to be an excellent model to study the processing of proenkephalin-A and chromogranins. Recently, we reported a study dealing with the processing of chromogranin B/secretogranin I and the occurrence of the C-terminal chromogranin B-derived peptide 614-626 which was shown to have antibacterial activity [Strub, J. M., Garcia-Sablone, P., Looning, K., Taupenot, L., Hubert, P., Van Dorsselaer, A., Aunis, D. & Metz-Boutigue, M. H. (1995) Eur J. Biochem. 229, 356-368]. We also observed that this new antibacterial activity present in chromaffin granules was associated with other endogenous protein-derived fragments yet to be characterized. The present study reports the isolation and characterization of a peptide which possesses antibacterial activity and which corresponds to the C-terminal 209-237 sequence of proenkephalin-A. A detailed study using microsequencing and matrix-assisted-laser-desorption time-of-flight mass spectrometry (MALD-TOF MS) allowed us to correlate the antibacterial activity of this peptide named enkelytin (FAEPLPSEEEGE-SYSKEVPEMEKRYGGFM) with post-translational modifications. Endogenous bisphosphorylated preen kephalin-A-(209-237) was active on Micrococcus luteus and Bacillus megaterium killing bacteria in the 0.2-0.4 mu M range but was inactive in similar conditions towards Escherichia coli. Enkelytin shares sequence and structural similarities with the antibacterial C-terminal domain of diazepam-binding inhibitor. According to this similarity, a prediction of secondary structure is proposed for enkelytin and discussed in relation to its biological activity.