Structure and mechanism of action of an indolicidin peptide derivative with improved activity against gram-positive bacteria
Structure and mechanism of action of an indolicidin peptide derivative with improved activity against gram-positive bacteria
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DOI：
10.1074/jbc.m009691200
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发表时间：
2001-06-29
影响因子：
4.8
通讯作者：
Hancock, REW
中科院分区：
文献类型：
--
作者：
Friedrich, CL;Rozek, A;Hancock, REW
Indolicidin是一种在牛中性粒细胞中发现的具有独特氨基酸序列（ILPWKWPWWPWRR-NH 2）的抗菌肽。indolicidin的衍生物CP 10A具有丙氨酸残基取代脯氨酸残基，并具有改善的抗革兰氏阳性生物体的活性。用CP 10A处理的金黄色葡萄球菌和表皮葡萄球菌的透射电子显微镜显示细胞质中的中粒体样结构。在最小抑制浓度的a倍的肽未显示对金黄色葡萄球菌ISP 67（组氨酸、尿苷和胸苷营养缺陷型）的显著杀伤，但确实显示对组氨酸和尿苷掺入的早期影响，以及随后对胸苷掺入的影响。在与脂质体，洗涤剂，和脂磷壁酸，CP 10A的相互作用，显示通过圆二色光谱进行二级结构的变化。荧光光谱表明色氨酸残基位于脂质体和洗涤剂胶束的疏水/亲水界面上，并且不能被水性猝灭剂KI所接近。使用二维NMR方法测定了脂质模拟物十二烷基磷酸胆碱中CP 10A的三维结构，其特征在于短的两亲性螺旋结构，而indolicidin先前显示具有延伸的结构。这些研究已经引入了具有独特结构和与膜相互作用并影响蛋白质、RNA和DNA的细胞内合成的能力的阳离子肽。
Indolicidin, an antimicrobial peptide with a unique amino acid sequence (ILPWKWPWWPWRR-NH2) is found in bovine neutrophils, A derivative of indolicidin, CP10A, has alanine residues substituted for proline residues and has improved activity against Gram-positive organisms. Transmission electron microscopy of Staphylococcus aureus and Staphylococcus epidermidis treated with CP10A showed mesosome-like structures in the cytoplasm, The peptide at a-fold the minimal inhibitory concentration did not show significant killing of S, aureus ISP67 (a histidine, uridine, and thymidine auxotroph) but did show an early effect on histidine and uridine incorporation and, later, an effect on thymidine incorporation. Upon interaction with liposomes, detergents, and lipoteichoic acid, CP10A was shown by circular dichroism spectroscopy to undergo a change in secondary structure. Fluorescence spectroscopy indicated that the tryptophan residues were located at the hydrophobic/hydrophilic interface of liposomes and detergent micelles and were inaccessible to the aqueous quencher KI. The three-dimensional structure of CP10A in the Lipid mimetic dodecylphosphocholine was determined using two-dimensional NMR methods and was characterized as a short, amphipathic helical structure, whereas indolicidin was previously shown to have an extended structure. These studies have introduced a cationic peptide with a unique structure and an ability to interact with membranes and to affect intracellular synthesis of proteins, RNA, and DNA.