一个与阴子结合的多药物和有毒化合物挤出输送器的结构
Xiao He1, Paul Szewczyk, Andrey Karyakin
1Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, CB105, La Jolla, California 92037, USA.
Nature
|September 24, 2010
概括
研究人员确定了MATE输送器的结构,这对植物代谢物运输和药物耐药性至关重要. 这揭示了其面向外的形状和独特的结构,与其他多药物耐药性转运器不同.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 多种药物和有毒化合物挤出 (MATE) 家族的载体对于植物中的代谢物运输至关重要,并在各种生物体中介导多种药物耐药性 (MDR).
- MATE输送器是MDR输送器的最后一个未确定类别,影响作物产量和制药药物的疗效.
- 这些传送器将基质运输与电化学梯度结合起来.
研究的目的:
- 为了确定来自Vibrio cholerae的MATE传送器NorM的X射线结构.
- 阐明MATE传送器功能的结构基础及其独特的拓.
- 确定潜在的阴离子结合点及其与运输机制的关系.
主要方法:
- 使用X射线晶体学来确定NorM传送器的结构.
- 进行了结构分析,以确定跨膜螺旋和潜在的结合部位等关键特征.
主要成果:
- 诺姆的X射线结构被确定为3.65 Å,显示出面向外的形状.
- 该结构具有独特的拓结构,有12个跨膜螺旋,与其他已知的MDR传送器不同.
- 在运输关键的残留物附近确定了一个阴离子结合点,这表明它在基质结合或运输调制中发挥了作用.
结论:
- 确定的结构为我们提供了第一次了解MATE传送器的形状.
- 独特的结构特征和已识别的阴离子结合部位为人们提供了关于运输机制的见解.
- 这些结构信息对于理解植物生理学和药物耐药性中的MATE传送器功能至关重要,并可能指导未来的药物开发.
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