Targeting Membrane Transport Steps in Cell Envelope Assembly

细胞包膜组装中的靶向膜运输步骤

基本信息

批准号：
10386887
负责人：
Daniel Kahne
金额：
$ 72.67万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-21 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10386887
关键词：
ATP-Binding Cassette Transporters Acinetobacter baumannii Address Affinity Amino Acids Amino Acyl-tRNA Synthetases Antibiotics Bacteria Biochemical Biochemistry Biogenesis Biological Assay Biology Carrier Proteins Cell surface Cells Cellular Structures Complex Crystallization Data Development Disaccharides Drug resistance Escherichia coli Face Family Genus Mycobacterium Glycolipids Gram-Negative Bacteria Health Human Impairment Infection Lead Lipid A Lipid Binding Lipids Lipopolysaccharides Maps Membrane Methods Molecular Conformation Monitor Mycobacterium tuberculosis Mycolic Acid Organism Pathway interactions Peptidoglycan Permeability Pharmaceutical Preparations Polymers Polysaccharides Process Proteins Public Health Pump Research Resistance Role Side Structure Surface Therapeutic Uses Toxic effect Transmembrane Transport Trehalose Variant Work cell envelope improved inhibitor multidisciplinary muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol novel novel strategies novel therapeutics periplasm resistance frequency small molecule structural biology sugar therapeutic development tool transport inhibitor tuberculosis treatment

项目摘要

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.

项目概要/摘要革兰氏阴性菌和结核分枝杆菌（Mtb）引起的感染对人类构成严重威胁这些生物体产生特别复杂的细胞膜，由双层膜组成。这对于生存至关重要。这种细胞膜还起到物理屏障的作用，阻止许多人进入。本研究旨在了解抗生素的类别，从而使其无效。负责细胞包膜组装的三种蛋白质转运蛋白的结构和功能。运输者代表三大运输者家族之一，即ABC运输者、MOPS 运输商和 RND 运输商了解这些运输商如何运输其复杂的糖脂货物，将进行转运和组装的中间体和抑制剂的生化和结构研究。将从结构、生物化学和细胞中表征更好地了解这些蛋白质的作用。细胞包膜组装将带来治疗耐药感染的新疗法。