Pellegrini A, Thomas U, Bramaz N, Klauser S, Hunziker P, von Fellenberg R
Institute of Veterinary Physiology, University of Zürich, Switzerland.
Biochem Biophys Res Commun. 1996 May 15;222(2):559-65. doi: 10.1006/bbrc.1996.0783.
Aprotinin is a protein proteinase inhibitor of 58 amino acids, located in bovine mast cells which also possesses antibacterial activity. Digestion of aprotinin by clostripain yielded three antimicrobial oligopeptide fragments with the sequences RPDFCLEPPYTGPCK (residues 1-15), IIRYFYNAKAGLCQTFVYGGCR (residues 18-39) and AKRNNFKSAEDCMRTCGGA (residues 40-58). With the exception of residues 16 (alanyl) and 17 (arginyl) they cover the whole aprotinin structure. The three oligopeptides were synthesized and found to exert a broad spectrum of antimicrobial activities. Most potent was oligopeptide IIRYFYNAKAGLCQTFVYGGCR which at a concentration of 7 x 10(-9) M exhibited a high bactericidal activity against the eleven gram-positive and gram-negative bacterial strains tested. None of the purified oligopeptides showed any antiproteolytic activity. Our results suggest that aprotinin has multiple antimicrobial domains which are independent of the antiproteolytic function of the original molecule.
抑肽酶是一种由58个氨基酸组成的蛋白质蛋白酶抑制剂，存在于牛肥大细胞中，也具有抗菌活性。用梭菌蛋白酶消化抑肽酶产生了三个抗菌寡肽片段，其序列分别为RPDFCLEPPYTGPCK（第1 - 15位氨基酸）、IIRYFYNAKAGLCQTFVYGGCR（第18 - 39位氨基酸）和AKRNNFKSAEDCMRTCGGA（第40 - 58位氨基酸）。除了第16位（丙氨酰）和第17位（精氨酰）氨基酸外，它们覆盖了抑肽酶的整个结构。合成了这三个寡肽，发现它们具有广谱抗菌活性。最有效的是寡肽IIRYFYNAKAGLCQTFVYGGCR，在浓度为7×10⁻⁹ M时，对所测试的11种革兰氏阳性和革兰氏阴性细菌菌株表现出高杀菌活性。纯化的寡肽均未显示出任何抗蛋白水解活性。我们的结果表明，抑肽酶具有多个抗菌结构域，这些结构域独立于原始分子的抗蛋白水解功能。
