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A Protocol for Computer-Based Protein Structure and Function Prediction
Published on: November 3, 2011
在两个结构上不同的酶中,类似功能的融合进化
J Kuriyan1, T S Krishna, L Wong
1Rockefeller University, New York 10021.
Nature
|July 11, 1991
概括
通过比较大肠杆菌铁素减少酶和人体谷氨减少酶,尽管具有相似的催化功能,但活性部位结构显然不同. 这种结构差异表明,它们的二硫化还原酶活动从共同的祖先独立演化.
科学领域:
- 酶学 是一种酶学.
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 铁素减少酶和谷氨减少酶是二元酶,通过皮里丁核酸,黄素和一种酶减少硫化物来催化二硫化物减少.
- 人类的谷氨还原酶具有四个不同的结构域,包括FAD和NADPH结合域,一个中心域,以及对于二分化和活性位点形成至关重要的C终端域.
- 尽管这些酶具有相同的催化机制和整体的三级结构,但它们在活性部位的配置上存在显著差异.
研究的目的:
- 阐明埃舍里希亚大肠杆菌硫氨酸减少酶和人类谷氨酸减少酶之间活性位点的差异的结构基础.
- 为了比较大肠杆菌硫素减少酶的四级结构和域组织与人体谷氨减少酶.
主要方法:
- 在2安格斯特罗姆分辨率下确定大肠杆菌硫素还原酶的晶体结构.
- 对大肠杆菌硫素减少酶和人类谷氨减少酶进行比较结构分析.
主要成果:
- 晶体结构显示,大肠杆菌的硫素还原酶缺乏人体谷氨还原酶中存在的C端域,它形成了二分体接口.
- 与人类的谷氨缩小酶相比,大肠杆菌氨缩小酶形成了一个独特的二维结构.
- 催化必不可少的二硫化基位于不同的领域,并且位于两个酶中flavin环系统的对面.
结论:
- 结构上的差异,特别是域组成和活性位点的排列,表明大肠杆菌硫素减少酶和人体谷氨减少酶已经发展出不同的二硫化物减少机制.
- 这些发现支持了这些酶从祖先的核酸结合蛋白中分离出来,并独立地获得了各自的二硫化还原酶功能的假设.
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