结构生物学 结构生物学. 通过交替的质子转位和化物转移来转化酶中的分工
Josephine H Leung1, Lici A Schurig-Briccio2, Mutsuo Yamaguchi1
1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
概括
尼古丁胺核酸转酶 (TH) 产生NADPH,这对细胞氧化应激防御至关重要. 结构分析揭示了一种不对称的二元机制,用于质子转位和化物转移.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 细胞的新陈代谢
背景情况:
- 维持细胞氧化还原平衡对于对抗氧化应激至关重要.
- 尼古丁胺核酸转酶 (TH) 是一种关键的膜酶,将质子梯度与NADPH生产联系起来.
- NADPH对于许多细胞还原生物合成和抗氧化途径至关重要.
研究的目的:
- 阐明尼古丁胺核酸转酶 (TH) 功能的结构基础.
- 为了提供对NADPH生成机制的洞察力,与质子动力相结合.
- 描述来自Thermus thermophilus的TH酶的结构特征.
主要方法:
- 使用X射线结晶学来确定TH酶的结构.
- 获得了超膜质子通道域和整个全酶的高分辨率晶体结构.
- 结构分析侧重于维度安排和域定向.
主要成果:
- TH的跨膜域结晶成一个对称的二元体,每个质子体都有一个质子通道.
- 整酶 (holo-TH) 呈现为一个高度不对称的二次体.
- NADP (H) 结合域 (dIII) 在不对称的全TH二次体内表现出两种不同的方向.
结论:
- 整体TH的不对称二元结构表明了一个新的催化机制.
- NADP (H) 结合域的两个副本可能在质子转位和化物转移中交替发挥作用.
- 这种结构性的洞察力有助于我们对细胞氧化还原恒温和能量转导的理解.
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