ENERGETICS OF AN ANION-TRANSLOCATING ATPASE

阴离子转运ATP酶的能量

• 批准号: 3432675
• 负责人: BARRY P. ROSEN
• 金额: $ 2.5万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3432675
• 关键词: active transport; adenosinetriphosphatase; anions; antimony; arsenic; bioenergetics; drug resistance; membrane potentials; membrane transport proteins; mitochondria; operon; plasmids

The overall goals of this research are first, elucidation of the molecular mechanisms of an ion pump whose genes are natural components of a bacterial resistance plasmid, and second, the role of this transport system in bacterial resistance to antibiotics and toxic compounds. The clinical resistance plasmid R773 carries the arsenical resistance (ars) operon, which produces resistance to arsenate, arsenite, and antimonite. The operon encodes an oxyanion-translocating ATPase which functions as an ATP-coupled extrusion pump for the toxic oxyanions. In this collaborative project analysis will be extended to determine the energetics of this novel anion pump, with the specific aim of determination of the mechanism of energy coupling. The laboratory of Professor V.P. Skulachev pioneered the methodology for the measurement of membrane potentials and ion fluxes in mitochondria, submitochondrial particles, bacteria and bacterial membrane vesicles. Professor Skulachev is uniquely qualified to perform these collaborative studies. While plasmid-mediated antibiotic and heavy metal resistances which are due to energy-dependent efflux systems may be wide spread in nature, anion pumps appear to be rather rare. The arsenical efflux system provide a good model system for the study of transmissible bacterial antibiotic resistances. The plasmid encoded ars system also provides a bacterial model for the study of multidrug resistance in mammalian cells. The Ars ATPase exhibits structural and functional similarity to the P-glycoprotein, the protein which produces multiple drug resistance in tumor cells.

本研究的总体目标是，首先，阐明 离子泵的分子机制，其基因是 细菌耐药质粒，第二，这种转运的作用 细菌对抗生素和有毒化合物的耐药性系统。 的 临床抗性质粒R773携带砷抗性（ars） 操纵子，产生对砷酸盐、亚砷酸盐和亚锑酸盐的抗性。 操纵子编码氧阴离子转运ATP酶，其功能为 ATP耦合的有毒含氧阴离子挤出泵。 在这个合作项目中，分析将扩展到确定 这种新型阴离子泵的能量学，其具体目的是 能量耦合机制的确定。 实验室 V. P. Skulachev教授开创了测量 线粒体、亚线粒体膜电位和离子流 颗粒、细菌和细菌膜囊泡。 斯库拉切夫教授 是唯一有资格进行这些合作研究的人 而质粒介导的抗生素和重金属抗性， 由于依赖能量的外排系统在自然界中广泛分布， 阴离子泵似乎相当罕见。 砷外排系统 为传染性细菌的研究提供了一个良好的模型系统 抗生素耐药性 质粒编码的ars系统还提供了一种 细菌模型，用于研究哺乳动物细胞中的多药耐药性。 Ars ATP酶在结构和功能上与 P-糖蛋白是一种在大肠杆菌中产生多药耐药的蛋白质， 肿瘤细胞