STRUCTURAL CHANGES IN MULTI-DRUG TRANSPORTER HOMOLOG MSBA FROM ECOLI

ECOLI 多药物转运蛋白同源物 MSBA 的结构变化

• 批准号: 7956624
• 负责人: Hassane S Mchaourab
• 金额: $ 0.22万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956624
• 关键词: ATP Hydrolysis; ATP-Binding Cassette Transporters; Binding; Cell membrane; Computer Retrieval of Information on Scientific Projects Database; Detergents; Development; Disease; Environment; Funding; Grant; Homologous Gene; Hydrolysis; Institution; Lipid A; Lipids; Lipopolysaccharides; Medical; Methods; Multi-Drug Resistance; P-Glycoprotein; P-Glycoproteins; Pharmaceutical Preparations; Research; Research Personnel; Resources; Source; Structure; Technology; United States National Institutes of Health; Vesicle; X-Ray Crystallography; base; multi drug transporter; novel therapeutics

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Multidrug resistance is a serious medical problem and presents a major challenge to the treatment of disease and the development of novel therapeutics. ABC transporters that are associated with multidrug resistance move hydrophobic drugs and lipids from the inner to the outer leaflet of the cell membrane. E.coli MsbA lipopolysaccharide (lipid A) flippase is homolog of mammalian P-glycoproteins. Different transporters are thought to have a common mechanism based on ATP binding and hydrolysis to energize the substrate translocation. The structure of MsbA in vesicles is different from that in detergent used in X-ray crystallography. Therefore, the study of MsbA conformational changes produced by ATP hydrolysis in the lipid environment is valuable, but requires methods suited for such case. Distance constraints from ESR are well up to the task. We plan to determine a critical set of such constraints to undersand better the MsbA conformational changes.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 多重耐药性是一个严重的医学问题，对疾病的治疗和新疗法的开发提出了重大挑战。与多药耐药性相关的 ABC 转运蛋白将疏水性药物和脂质从细胞膜的内层转移到外层。大肠杆菌 MsbA 脂多糖（脂质 A）翻转酶是哺乳动物 P-糖蛋白的同源物。 不同的转运蛋白被认为具有基于 ATP 结合和水解的共同机制，为底物易位提供能量。囊泡中 MsbA 的结构与 X 射线晶体学中使用的洗涤剂中的结构不同。因此，研究脂质环境中 ATP 水解产生的 MsbA 构象变化是有价值的，但需要适合这种情况的方法。 ESR 的距离限制完全可以胜任这项任务。 我们计划确定一组关键的此类约束，以更好地理解 MsbA 构象变化。