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多药结合转录因子QacR在多个位置结合了双价芳香二胺丁DB75和DB359
Benjamin E Brooks1, Kevin M Piro, Richard G Brennan
1Department of Biochemistry and Molecular Biology, University of Texas MD Anderson Cancer Center, Unit 1000, Houston, TX 77030, USA.
Journal of the American Chemical Society
|June 15, 2007
概括
黄金葡萄球菌 QacRR
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QacR是一种转录抑制剂,可以结合多种药物.
- 它的结合口袋包括更小,重叠的"迷你口袋",促进各种分子相互作用.
- 药物结合通常涉及堆叠,范德瓦尔斯和离子力,具有有限的结合.
研究的目的:
- 为了研究双价胺与QacR的结合机制.
- 为了确定QacR-DB75和QacR-DB359复合物的晶体结构.
- 测量这些化合物与QacR.的结合亲和力.
主要方法:
- 使用X射线晶体学来确定QacR药物复合物的结构.
- 使用生物物理技术测量了结合亲和力.
- 在QacR结合口袋中的药物蛋白相互作用的分析.
主要成果:
- 像DB75和DB359这样的双对应胺胺与低微分子亲和度的QacR结合.
- 这些化合物没有单个,离散的结合模式.
- 结合相互作用涉及通过双极相互作用中和正电荷,而不是仅仅是离子键.
结论:
- QacR多药结合口袋表现出显著的化学冗余,允许杂乱结合.
- 这种化学冗余是许多多药结合囊的可能特征.
- 只有特定的药物类别,如刚性,双价化合物,才能有效利用这种冗余性.
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