Targeting Membrane Transport Steps in Cell Envelope Assembly

项目摘要/摘要 革兰氏阴性菌和结核分枝杆菌感染对人类构成严重威胁 健康。这些生物产生特别复杂的由双层膜组成的细胞膜。 对生存至关重要的生物。该单元格包膜还起到物理屏障的作用，阻止许多 抗生素的种类，从而使其无效。这项研究旨在了解 负责细胞被膜组装的三种蛋白质转运体的结构和功能。这其中的每一个 运输商代表三大运输商家族之一，即ABC运输商，MOPS 传送器和RND传送器。为了了解这些转运体是如何移动它们复杂的糖脂货物的， 将进行生化和结构研究。转运和组装的中间体和抑制剂 将在结构上、生化上和细胞内进行表征。更好地了解这些蛋白质在 细胞膜组装将导致治疗耐药感染的新疗法。

Project Summary/Abstract Infections due to Gram-negative bacteria and mycobacterium tuberculosis (Mtb) pose a serious threat to human health. These organisms produce especially complex cell envelopes consisting of a double layer of membranes that are essential for survival. This cell envelope also functions as a physical barrier to block entry of many classes of antibiotics and thereby render them ineffective. This research is directed towards understanding the structure and function of three protein transporters responsible for cell envelope assembly. Each of these transporters represents one of the three major transporter families, namely ABC transporters, MOPS transporters, and RND transporters. To understand how these transporters move their complex glycolipid cargo, biochemical and structural studies will be undertaken. Intermediates and inhibitors of transport and assembly of will be characterized structurally, biochemically, and in cells. A better understanding of these proteins’ roles in cell envelope assembly will lead to new therapies to treat resistant infections.