QacR诱导和多药物识别的结构机制
M A Schumacher1, M C Miller, S Grkovic
1Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97201, USA.
Science (New York, N.Y.)
|December 12, 2001
概括
黄金葡萄球菌多药结合蛋白QacR在结合各种药物时发生结构变化,揭示了其控制多药耐药基因的机制.
科学领域:
- 微生物学 微生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 黄金葡萄球菌具有一种多药结合蛋白,QacR,它调节了qacA多药转运基因.
- QacR的转录抑制是由各种性脂性药物诱导的,这表明一个复杂的调节机制.
研究的目的:
- 阐明QacR药物结合和转录调节的结构基础.
- 了解QacR如何与多种药物相互作用.
主要方法:
- 采用X射线结晶学来确定六种QacR药物复合物的结构.
- 药物结合结构与先前确定的DNA结合结构的比较.
主要成果:
- 药物结合在QacR.中诱导了显著的线圈到螺旋结构过渡.
- 这种过渡形成了一个大型的多药结合口袋,其中含有特定的氨基酸残留物 (谷氨酸,芳香物,极性残留物).
- 结合口袋似乎包含QacR蛋白内多个相互连接的药物结合点.
结论:
- 晶体结构揭示了QacR.中的一个新的多站点药物结合机制.
- 这种机制解释了QacR如何结合各种药物并调节qacA基因.
- 这些发现提供了对多药性耐药性传递机制的见解.
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