对细菌NADPH氧化酶的X射线结构和酶研究突出显示了真核生物NOX的激活机制
Isabelle Petit-Hartlein1, Annelise Vermot1, Michel Thepaut1
1Univ. Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale, Grenoble, France.
eLife
|April 19, 2024
概括
肺炎 estreptococcus 的 NADPH 氧化酶 (SpNOX) 揭示了化物从 NAD 转移到 FAD 的速度限制步骤. 这种构成性酶为更广泛的NADPH氧化酶 (NOX) 家族的激活机制提供了洞察力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 酶学 是一种酶学.
背景情况:
- NADPH氧化酶 (NOX) 是关键的跨膜蛋白,用于细胞功能产生活性氧物种 (ROS).
- ROS信号传递和天生的免疫力依赖NOX活动,但它们的电子转移激活机制尚不清楚.
- 肺炎 estreptococcus NOX (SpNOX) 是一个构成性活跃的同类物,可以作为NOX家族研究的宝贵模型.
研究的目的:
- 阐明NADPH氧化酶 (NOX) 的电子转移机制和激活过程.
- 研究SpNOX活动的结构基础及其作为人类NOX异型的模型的作用.
- 为了确定关键的残留物和涉及 SpNOX 中基质结合和电子转移的域.
主要方法:
- 确定全长SpNOX及其脱酶 (DH) 域的晶体结构.
- 生物化学试验分析基质使用 (NADPH/NADH) 并确定速度限制步骤.
- 与相关酶进行比较分析,以了解域相互作用和激活.
主要成果:
- 晶体结构揭示了SpNOX DH域功能作为flavin减少酶,利用NADPH和NADH.
- 从NAD(P) H到FAD的化物转移被确定为SpNOX电子转移中的速度限制步骤.
- 残留物F397对于尼古丁胺进入黄来说至关重要,DH和转膜 (TM) 域都对黄结合有贡献.
结论:
- SpNOX激活涉及DH域内的内部重组,从静止状态过渡到活跃状态.
- 该研究提出了SpNOX的模型,提供了对NOX2.2的激活要求的见解.
- 结构和机械学的发现有助于我们更好地理解NOX酶家族中的电子转移.
关键词:
在NADPH氧化酶.链球菌肺炎的肺炎.生物化学 生物化学化学生物学 化学生物学电子转移是电子的转移.酶激活酶的激活方式人类 人类 人类 人类 人类 人类 人类作为一个完整的膜蛋白质.分子生物物理学分子生物物理学有活性氧物种的反应性氧物种.结构生物学结构生物学更多相关视频
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