转录激活剂BmrR结合DNA和一种药物的晶体结构
1Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland 97201-3098, USA.
Nature
|February 24, 2001
概括
细菌的多药性耐药性通常是由药物排泄引起的. 这项研究揭示了BmrR (转录调节剂) 如何通过打破和滑动DNA基因对来激活传送基因表达,这是一种控制抗性的新机制.
科学领域:
- 分子生物学分子生物学
- 微生物学 微生物学
- 结构生物学 结构生物学
背景情况:
- 细菌的多药性耐药性 (MDR) 是一个重大的临床挑战,通常由膜跨度药物排放载体介导.
- 这些载体的表达通常由与有毒化合物结合的转录因子调节,例如Bacillus subtilis中的BmrR.
研究的目的:
- 阐明MerR家族转录调节器BmrR激活多药载体基因 (bmr) 转录的结构机制,以应对药物结合.
- 了解转录激活的分子基础,包括促进子重构.
主要方法:
- 使用X射线晶体学来确定BmrR.的3.0 Å分辨率结构.
- 结构被确定为复合物,使用药物四基 (TPP) 和含有BMR促进子序列的DNA寡氧核酸.
主要成果:
- 晶体结构显示BmrR与TPP结合,以及bmr促进体DNA.
- 观察到一种意想不到的转录激活机制,涉及局部DNA基对破坏,滑动和 -35和 -10促进元件的重新调整.
- 这种重新配置促进了与RNA聚合酶的有效相互作用.
结论:
- BmrR采用一种独特的转录激活机制,涉及DNA结构重组,以对抗毒性化合物暴露.
- 了解这种机制可以了解细菌的多药耐药性和治疗干预的潜在目标.
相关概念视频
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