诱导的酸性转移在S100A1212的抗菌封存中的分子基础
Mahil Kothalawala1,2, Shaan Shirazi1, Qian Wang1
1Department of Chemistry, College of Staten Island, City University of New York, New York, New York 10314, United States.
The journal of physical chemistry. B
|September 19, 2025
概括
抗微生物蛋白S100A12使用His3Asp动机结合 (Zn(II)) 来对抗感染. (Ca(II)) 结合变化Zn(II) 化,在炎症期间在较低的pH值保持抗微生物活性.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 金属蛋白化学 金属蛋白化学
背景情况:
- 抗菌蛋白S100A12通过His3Asp动机利用 (Zn(II)) 化来抑制病原体.
- 了解S100A12的pH依赖性Zn(II) 结合对于其在感染和炎症中的作用至关重要.
研究的目的:
- 通过S100A12在不同与感染相关的pH条件下研究Zn(II) 结合的分子机制.
- 阐明 (Ca(II)) 结合对S100A12.12的Zn(II) 结合特性和结构动态的影响.
主要方法:
- 紫外线可见 (UV-vis) 光谱测试以评估的结合亲和力作为pH值的函数.
- 核磁共振 (NMR) 光谱检测结构变化和质子事件.
- 分子动力学 (MD) 模拟来分析盐桥的形成和结构动力学.
主要成果:
- 与apo-S100A12结合的Zn(II) 显示出西格形pH依赖性,pH值在7.0以下显著下降.
- 与S100A12结合的Ca (II) 将Zn (II) 的结合曲线转移到较低的pH值,扩展其亲和力.
- 核磁共振和核磁共振模拟显示pH诱导的构造变化和盐桥形成在His3Asp动机内,它们是由Ca(II) 调节的.
结论:
- 对His3Asp基因的质子化导致Zn(II) 结合的丧失和稳定的盐桥的形成.
- 在中性pH下,Ca (II) 结合会阻碍盐桥形成,从而在炎症期间发现的酸性pH下保持S100A12的Zn (II) 结合亲和力.
- 这些发现为S100A12作为抗微生物剂的pH调节功能提供了分子洞察力.
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