通过BmrR进行多药物识别的结构基础,BmrR是多药物载体的转录激活剂
E E Zheleznova1, P N Markham, A A Neyfakh
1Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201-3098, USA.
Cell
|February 20, 1999
概括
细菌细菌BmrR蛋白通过展开一个alpha螺旋来暴露一个口袋来结合各种药物. 这种结合机制涉及水和静电相互作用,是多药耐药性的关键.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 多种药物外流输送器可以识别各种毒素.
- 细菌细菌的转录调节器 BmrR 结合了疏水性阴阳性药物.
- 在药物结合时,BmrR激活了多药物载体Bmr的表达.
研究的目的:
- 通过BmrR阐明药物结合的结构基础.
- 了解BmrR中药物识别和选择性的机制.
主要方法:
- BmrR多药结合域的X射线晶体学.
- 在2.7分辨率和2.8A分辨率下确定BmrR-tetraphenylphosphonium复合物的晶体结构.
主要成果:
- 药物结合诱导了BmrR.中的α螺旋体的展开和转移.
- 一个内部的药物结合口袋暴露在螺旋运动时.
- 基的结合涉及水和静电相互作用,包括与埋藏的谷氨酸残留的关键相互作用,以获得离子选择性.
结论:
- 对于结合,BmrR采用一种独特的药物诱导的形状变化.
- 埋藏的谷氨酸残留物对BmrR的阳离子选择性至关重要.
- 类似的结合原理也可能适用于其他多药结合蛋白.
相关概念视频
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RNA...
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