Targeting Membrane Transport Steps in Cell Envelope Assembly

细胞包膜组装中的靶向膜运输步骤

• 批准号: 10610387
• 负责人: Daniel Kahne
• 金额: $ 72.67万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 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/10610387
• 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; Collaborations; Complex; Cytoplasm; Data; Development; Disaccharides; Drug resistance; Escherichia coli; Face; Family; Genus Mycobacterium; Glycolipids; Gram-Negative Bacteria; Health; Human; Impairment; Infection; Lipid A; Lipid Binding; Lipids; Lipopolysaccharides; Maps; Membrane; Methods; Molecular Conformation; Monitor; Mycobacterium tuberculosis; Mycolic Acid; Organism; Pathway interactions; Penetration; 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 assembly; 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

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.

项目总结/文摘