在dTDP-d-葡萄糖脱水酶 (RmlB) 酶中NADH的结构
Konstantinos Beis1, Simon T M Allard, Adrian D Hegeman
1Centre for Biomolecular Sciences, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9ST, United Kingdom.
Journal of the American Chemical Society
|September 25, 2003
概括
瑞波菌 suis RmlB 酶结构揭示了NADH的独特的船形状. 这种由键稳定下来的形状变化,微调了NADH的微调.
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:
- 菌株Streptococcus suis RmlB (dTDP-d-glucose 4,6-dehydratase) 对于细菌细胞壁的合成至关重要.
- 了解RmlB的机制是开发新型抗生素的关键.
- 以前的结构显示在辅因子中有一个平面的尼古丁胺胺环.
研究的目的:
- 为了阐明RmlB酶活性的结构基础.
- 为了研究辅因子构成在酶催化中的作用.
- 为了确定RmlB与结合的尼古丁胺合酶和基质模拟物的结构.
主要方法:
- 在1.5A分辨率的X射线晶体学.
- 单晶光谱学研究.
- 一开始的电子结构计算.
主要成果:
- 确定了RmlB在与NADH和dTDP-xylose一起的流产复合体中的结构.
- 观察到NADH的二胺环的船形构造,与本地结构不同.
- 确定了一种内部键,稳定了船形状.
- 计算表明,这种构造影响NADH的化物供体能力和氧化还原潜力.
结论:
- 脱水酶可以通过尼古丁胺环形状变化调节NADH氧化还原潜力.
- 活性部位的氨酸残留物可能进一步影响化物转移.
- 该研究提供了对酶催化机制和潜在药物点的见解.
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