酶活性在一个祖先的糖转移酶中的演变
Jorick Franceus1, José Pablo Rivas-Fernández2, Jolien Lormans1
1Centre for Synthetic Biology (CSB), Department of Biotechnology, Ghent University, Coupure Links 653, Ghent 9000, Belgium.
概括
祖先序列重建揭示了曼诺酸酶活性如何在Leishmania寄生虫中演变. 在活性部位之外的微妙突变使这种关键的碳水化合物活性酶功能成为可能.
科学领域:
- 生物化学 生物化学
- 分子进化分子进化
- 结构生物学 结构生物学
背景情况:
- 碳水化合物活性酶对于合成和降解曼诺基因至关重要,曼诺基因是Leishmania寄生虫的关键碳水化合物储备.
- 了解这些酶的演变,可以了解塑造现代蛋白质的适应性途径.
研究的目的:
- 重建和描述Leishmania中参与曼诺基因代谢的祖先碳水化合物活性酶.
- 为了研究曼诺酸酶活性进化的出现和丧失.
主要方法:
- 祖先序列重建和复活酶的生化特征.
- 通过局部定向突变发生的历史序列空间的分析.
- 分子动力学模拟以阐明酶活性的结构基础.
主要成果:
- 曼诺酸酸化酶的活性源于一个祖先的细菌曼诺转移酶,随后在Leishmania中消失了.
- 在活性部位以外的特定突变足以恢复曼诺酸酶活性.
- 远端突变影响活性部位的灵活性和防水,促进生产基质的构成.
结论:
- 蛋白质进化可以由微妙的,远端突变驱动,这些突变调节酶活性和基质结合.
- 祖先的糖转移酶作为工程新型酸化酶的有价值的模板.
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