CRYSTALLOGRAPHIC STUDIES OF TRANSPORT PROTEINS FROM ESCHERICHIA COLI

大肠杆菌转运蛋白的晶体学研究

• 批准号: 6240606
• 负责人: HIROSHI NIKAIDO
• 金额: $ 16.99万
• 依托单位: UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6240606
• 关键词: Escherichia coli; bacterial proteins; bacterial toxins; cell membrane; cell wall; crystallization; maltose; membrane transport proteins; pore forming protein; protein structure; transmission electron microscopy

The goal of this subproject is to purify in sufficient amounts two intrinsic membrane proteins of Escherichia coli, the OmpA protein of the outer membrane and the multi-subunit, maltose transporter complex of the inner, cytoplasmic membrane, and to carry out the electron crystallographic studies of these membrane proteins. OmpA was chosen because it belongs to a family of novel porins, with unusually low permeability, and the structural basis for this property is total unknown. The elucidation of the channel structure of this protein is expected to help design better chemotherapeutic agents, which would be more effective against Pseudomonas aeruginosa, that is a major source of opportunistic infections because it has an OmpA homolog, a low permeability porin, as its main porin. The maltose transporter complex was chosen because it is one of the best-studied members of a widespread transporter family, the ABC ("ATP-binding cassette") transporters, and much knowledge is available on the physiology and genetics of this transporter. The ABC transporters include the MDR system of mammalian cells, which pumps out anti-cancer agents from the cytoplasm of cancer cells. Thus the understanding of the molecular structure and mechanism of action of maltose transporter, as a paradigm of the ABC transporters, is expected to contribute to the design of anti-cancer agents that may remain active even in cells expressing the MDR system at a high level.

这个子项目的目标是在足够的数量净化两个 大肠杆菌的内在膜蛋白， 外膜和多亚基，麦芽糖转运蛋白复合物的 内，细胞质膜，并进行电子 这些膜蛋白的晶体学研究。 Ompa被选中 因为它属于一个新的孔蛋白家族， 渗透性，并且这种性质的结构基础完全未知。 这种蛋白质的通道结构的阐明有望 帮助设计更好的化疗药物， 铜绿假单胞菌，这是一个主要来源的机会 感染，因为它有一个OmpA同源物，低渗透性孔蛋白， 其主要孔。 选择麦芽糖转运蛋白复合物是因为它是 作为广泛分布的转运蛋白家族中研究得最好的成员之一， ABC（“ATP结合盒”）转运蛋白，并且许多知识是可用的 关于这个传送器的生理学和遗传学。 ABC运输公司 包括哺乳动物细胞的MDR系统， 从癌细胞的细胞质中提取药物。 所以，理解。 麦芽糖转运蛋白的分子结构和作用机制， ABC运输机的范例，预计将有助于设计 即使在表达抗肿瘤药物的细胞中， MDR系统处于高水平。