通过Alba的结构和功能显示的细菌多药耐药性系统的适应
Asfandyar Sikandar1, Katarina Cirnski2,3, Giambattista Testolin3,4
1Workgroup Structural Biology of Biosynthetic Enzymes, Helmholtz Institute for Pharmaceutical Research Saarland , Helmholtz Centre for Infection Research, Saarland University , Campus Geb. E8.1 , Saarbrücken 66123 , Germany.
Journal of the American Chemical Society
|November 14, 2018
概括
新的研究揭示了抗生素中和蛋白 AlbA 如何结合并改变抗生素阿尔比西丁. 这种蛋白质是从一个古老的基因进化出来的, 提供了对抗生素耐药性机制和潜在的新药发现策略的见解.
科学领域:
- 微生物学
- 结构生物学
- 药物发现
背景情况:
- 抗菌耐药性需要新型抗生素的发现.
- 阿尔比西丁和西斯托巴克塔米德是有效的抗生素,可以对抗阳性和阴性病原体.
- 阿尔比西丁中和蛋白A (AlbA) 是一种潜在的抗药性机制.
研究的目的:
- 阐明Alba与阿尔比西丁相互作用的结构基础.
- 了解 AlbA 中和 的机制.
- 为了研究Alba的进化起源.
主要方法:
- 用X射线结晶学测定Alba及其与阿尔比西丁复合物的结构.
- 生物化学测试以证明阿尔比西丁的修饰.
- 生物信息分析以推断进化关系.
主要成果:
- AlbA的结构显示了两个域,每个域都与多抗生素中和蛋白TipA相似.
- 阿尔比西丁结合在两个 AlbA 域中呈现伪对称的分布.
- 促使阿尔比西丁发生意想不到的化学变化,降低了它的功效.
结论:
- AlbA可能是通过内部复制从古老的TipA类基因进化而来的.
- 这些发现提供了对阿尔比西丁中和耐药性的结构理解.
- 这项工作提供了对抗生素结合蛋白的演变和新抗生素开发的潜在途径的见解.
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