Outer Membrane Biogenesis: New Antibiotic Targets

外膜生物发生：新的抗生素靶点

• 批准号: 8793724
• 负责人: Daniel Kahne
• 金额: $ 47.51万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-15 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8793724
• 关键词: Amino Acids; Antibiotic Resistance; Antibiotics; Binding; Binding Sites; Biochemical; Biogenesis; Biological Assay; C-terminal; Carrier Proteins; Cell surface; Cells; Complex; Consensus Sequence; Cyclic Peptides; Cytoplasm; Development; Escherichia coli; Glycolipids; Gram-Negative Bacteria; Health; Human; In Vitro; Individual; Infection; Lead; Length; Lipopolysaccharides; Lipoproteins; Membrane; Membrane Proteins; Methods; Modeling; Molecular; Molecular Structure; Movement; Mutation; Organism; Peptide Fragments; Peptide Signal Sequences; Peptides; Phospholipids; Point Mutation; Positioning Attribute; Process; Protein Binding; Proteins; Proteolysis; Pseudomonas aeruginosa; Relative (related person); Research; Resistance; Roentgen Rays; Site; Structure; Substrate Interaction; System; Testing; Therapeutic Uses; Work; crosslink; fluorophore; inhibitor/antagonist; insight; killings; membrane biogenesis; periplasm; protein folding; protein protein interaction; proteoliposomes; reconstitution; research study; small molecule; sugar; tool

DESCRIPTION (provided by applicant): Antibiotic resistant Gram-negative infections pose a serious threat to human health. The outer membrane of Gram-negative bacteria is a unique structure essential for survival; it 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 two multi-protein machines responsible for the biogenesis of two major components of the outer membrane, lipopolysaccharide (LPS) and outer membrane proteins (OMPs). To understand the protein-protein interactions within each machine and their molecular structures, biochemical and structural studies will be undertaken. To dissect the functions of the individual components of these machines, the assembly of LPS and OMPs will be reconstituted in vitro. A better understanding of the protein machinery and the processes in which they are involved may lead to the discovery of inhibitors that could ultimately be developed to treat Gram-negative infections.

描述（由申请人提供）：耐药革兰氏阴性感染对人类健康构成严重威胁。革兰氏阴性菌的外膜是生存所必需的独特结构；它还作为一个物理屏障，阻止许多种类的抗生素进入，从而使它们无效。本研究旨在了解负责外膜两种主要成分脂多糖（LPS）和外膜蛋白（OMPs）生物发生的两种多蛋白机器的结构和功能。为了了解每台机器中蛋白质之间的相互作用及其分子结构，将进行生化和结构研究。为了解剖这些机器的单个组件的功能，LPS和OMPs的组装将在体外重组。更好地了解蛋白质机制及其参与的过程可能会导致发现抑制剂，最终可能被开发用于治疗革兰氏阴性感染。