STRUCTURAL CHANGES IN MULTI-DRUG TRANSPORTER HOMOLOG MSBA FROM ECOLI

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 多药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小叶移动到外小叶。大肠杆菌MsbA脂多糖（脂质A）翻转酶是哺乳动物P-糖蛋白的同系物。 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，以激发底物转运。囊泡中MsbA的结构与X射线晶体学中使用的去污剂中的结构不同。因此，在脂质环境中ATP水解产生的MsbA构象变化的研究是有价值的，但需要适合这种情况的方法。 来自ESR的距离限制很好地完成了任务。 我们计划确定一个关键的一组这样的限制，更好地了解MsbA的构象变化。

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.