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首页> 外文期刊>Biochemistry >Structural Insights into the Mode of Action of the Peptide Antibiotic Copsin
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Structural Insights into the Mode of Action of the Peptide Antibiotic Copsin

机译：结构见解肽抗生素COPSIN的作用方式

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摘要

Defensins make up a class of cysteine-rich antimicrobial peptides, expressed by virtually all eukaryotes as part of their innate immune response. Because of their unique mode of action and rapid killing of pathogenic microbes, defensins are considered promising alternatives to clinically applied antibiotics. Copsin is a defensin-like peptide, previously identified in the mushroom Coprinopsis cinerea. It exerts its activity against a range of Gram-positive bacteria by binding to the peptidoglycan precursor lipid II and prevention of proper cell wall formation. In this study, we present a new workflow for the generation, production, and activity-driven selection of copsin derivatives, based on their expression in Pichia pastoris. One hundred fifty-two single-amino acid mutants and combinations thereof allowed the identification of k-copsin, a peptide variant exhibiting significantly enhanced activity against Bacillus subtilis and Staphylococcus aureus. Furthermore, we performed in silico characterizations of membrane interactions of copsin and k-copsin, in the presence and absence of lipid II. The molecular dynamics data highlighted a high variability in lipid II binding, with a preference for the MurNAc moiety with 47 and 35% of the total contacts for copsin and k-copsin, respectively. Mutated amino acids were located in loop regions of k-copsin and shown to be crucial in the perturbation of the bacterial membrane. These structural studies provide a better understanding of how defensins can be developed toward antibacterial therapies less prone to resistance issues.]]>
机译：<！[cdata [ src ='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bichaw/2017/bichaw.2017.56.issue-37/acs.biochem.7b00697/ 20170914 / Images / Medium / Bi-2017-00697V_0005.gif“> Defensins构成一类富含半胱氨酸的抗微生物肽，几乎所有真核生物都表达，作为其先天免疫应答的一部分。由于它们独特的动作模式和致病微生物的快速杀害，Defensins被认为是临床应用抗生素的有前途的替代品。 Copsin是一种类似于防御素样肽，以前在蘑菇中鉴定在蘑菇中，Coprinopsis inerea 。它通过与肽聚糖前体脂质II结合并预防适当的细胞壁形成，它施加对一系列革兰氏阳性细菌的活性。在这项研究中，基于它们在 Pichia Pastoris 中的表达式，我们为生成，生产和活动驱动的选择的新工作流程提供了一种新的工作流程。一百五十二种单氨基酸突变体及其组合允许鉴定K-Copsin，肽变体表现出对I>枯草芽孢杆菌的显着增强的活性，并且金黄色葡萄球菌葡萄球菌。此外，在脂质II的存在和不存在的情况下，我们在硅和K-copsin的膜相互作用中进行了胰岛素相互作用的表征。分子动力学数据突出了脂质II结合的高可变性，优先于莫尔克蛋白组分别具有47和35％的Copsin和K-Copsin的总触点。突变的氨基酸位于K-Copsin的环形区域中，并且在细菌膜的扰动中显示至关重要。这些结构研究提供了更好地理解Defensins如何对抗菌治疗的开发方式不太容易发生抗性问题。]]>

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  • 来源
    《Biochemistry》 |2017年第37期|共10页
  • 作者

    Marco Franzoi; Yasemin van Heuvel; Susanne Thomann; Nadia Schürch; Pauli T. Kallio; Paola Venier; Andreas Essig;

  • 作者单位

    Department of Biology University of Padova Via Ugo Bassi 58/B Padova 35131 Italy;

    Institute of Microbiology Swiss Federal Institute of Technology ETH Zurich CH-8093 Zurich Switzerland;

    Biology Division Spiez Laboratory Federal Office for Civil Protection CH-3700 Spiez Switzerland;

    Biology Division Spiez Laboratory Federal Office for Civil Protection CH-3700 Spiez Switzerland;

    Institute of Microbiology Swiss Federal Institute of Technology ETH Zurich CH-8093 Zurich Switzerland;

    Department of Biology University of Padova Via Ugo Bassi 58/B Padova 35131 Italy;

    Institute of Microbiology Swiss Federal Institute of Technology ETH Zurich CH-8093 Zurich Switzerland;

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  • 正文语种 eng
  • 中图分类 生物化学;
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