重新检查粉样前体蛋白的E2域:铁氧化酶,超氧化物和氧化物清理活动
Andrew T Poore1, Eli C Zuercher1, Gabriel Bury2
1Department of Chemistry, Purdue University, West Lafayette, Indiana 47906, United States.
Inorganic chemistry
|June 27, 2023
概括
粉样蛋白前体蛋白 (APP) 的E2域具有铁氧化酶活性,可以清除活性氧和物种,可能保护神经元免受阿尔茨海默病中的氧化应激.
科学领域:
- 生物化学 生化学
- 神经科学是一个神经科学.
- 结构生物学 结构生物学
背景情况:
- 粉样蛋白前体蛋白 (APP) 与阿尔茨海默病 (AD) 有关.
- APP的E2域的功能,特别是其拟议的铁氧化酶活性和在铁平衡中的作用,仍然不清楚.
- 矛盾的证据需要进一步调查E2域的生物化学特性.
研究的目的:
- 阐明APP E2领域中的铜结合场所的结构和功能特征.
- 为了研究Cu (II) -E2域的铁氧化酶活性.
- 评估E2域与活性氧物种 (ROS) 和活性物种 (RNS) 的反应性.
主要方法:
- 扩展的X射线吸收细结构 (EXAFS) 光谱学.
- 紫外线可见光谱学. 紫外线可见光谱学.
- 电子偏磁共振 (EPR) 光谱学.电子偏磁共振 (EPR) 光谱学.
- 酶分析测量铁的氧化,氧耗,超氧化基清除和过氧酸盐分解.
主要成果:
- 鉴定出了一种新的可变水联体,它与E2域中的Cu (II) 辅因子协调.
- 对Cu (II) -E2 (速度高达1.0 × 10^2 M^-1 s^-1) 观察到单次转换铁氧化活性.
- Cu(I) -E2与分子氧反应缓慢 (5.3 M^-1 s^-1),但对超氧化激素 (1.6 × 10^5 M^-1 s^-1) 和过氧酸盐 (1.1 × 10^5 M^-1 s^-1) 显著反应.
结论:
- APP E2 域表现出酶活性,在特定条件下作为铁氧化酶起作用.
- 它充当超氧化基的补充清除剂和有效的过氧酸盐去除剂.
- 这些活动表明E2域在神经元细胞外环境中对ROS/RNS损伤起着保护作用,特别是在铁流出部位附近.
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