通过识别一种新的进化关键子结构来绘制二二酸合成酶的演变性
Dwipanjan Sanyal1, A Shivram2, Deeptanshu Pandey3
1Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
International journal of biological macromolecules
|April 20, 2025
概括
了解蛋白质进化,如二二酸合成酶 (DHPS),是打击抗生素耐药性的关键. 针对关键的DHPS亚结构可以减缓药物耐药性的出现.
科学领域:
- 微生物学 微生物学
- 进化生物学 进化生物学
- 结构生物学 结构生物学
背景情况:
- 病原体的适应是由蛋白质进化驱动的,特别是在发展耐药性方面.
- 抗生素耐药性源于药物压力下的标蛋白的突变.
- 二甲酸合成酶 (DHPS) 是硫胺抗生素的关键点,突变会产生耐药性.
研究的目的:
- 了解DHPS破坏抗生素耐药性的进化动态.
- 确定关键的DHPS次序及其对演化性和药物适应性的影响.
主要方法:
- 对DHPS序列空间的统计分析.
- 深度突变分析与基于结构的网络拓模型集成.
- 挫折景观分析和基于经验的健身预测模型.
主要成果:
- 确定了影响构造性和突变性能量再分配的关键DHPS次序.
- 开发了一个健身预测模型,模拟适应性步行并识别关键的残留位置.
- 揭示了对DHPS演化能力至关重要的中央基层结构,并评估了其药物可用性.
结论:
- 结合进化和结构数据的综合框架识别了具有重大影响的DHPS子结构.
- 针对这个进化上受限且易于药物治疗的区域可能会减缓抗生素耐药性的出现.
- 这种方法为抗生素开发针对耐药病原体提供了新的方向.
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