在性酸酶超级家族中的性行为. 通过分子模拟来解开进化
Violeta López-Canut1, Maite Roca, Juan Bertrán
1Departament de Química Física, Universitat de València, 46100 Burjassot, Spain.
Journal of the American Chemical Society
|May 26, 2011
概括
大肠杆菌的性酸酶 (AP) 通过一种保守的解离机制,类似于其单酶活性,通过化酸. 蛋白质相互作用,特别是与Lys328的相互作用,决定了基质的特异性和混杂性.
科学领域:
- 生物化学 生物化学
- 计算生物学 计算生物学
- 酶学 是一种酶学.
背景情况:
- 大肠杆菌的性酸酶 (AP) 主要是一种单酶,但表现出乱的酶活性.
- 了解AP的二水解机制对于酶工程和药物设计至关重要.
研究的目的:
- 理论上研究AP活性部位中基化 (p-nitrophenyl酸甲基) 的性水解机制.
- 为了阐明AP的杂乱的化酶活性和基质特异性的分子基础.
主要方法:
- 使用了分子动力学 (MD) 模拟.
- 混合量子力学/分子力学 (QM/MM) 潜能被用来建模反应.
- 分析的重点是水解过程中AP活性部位内的相互作用.
主要成果:
- 反应通过D(N) A(N) 或分离机制进行,与单水解相一致.
- 特定的蛋白质相互作用,涉及Mg2+) 协调水和Lys328,稳定单基质,但阻碍了二水解.
- 在Lys328中发生的突变增强了AP的死酶活性.
- 酶乱交是通过中心和外部遗留物稳定离开群体中的多样性电荷分布引起的.
结论:
- 保存的分离机制解释了AP的散乱的化酶活性.
- 蛋白质基质相互作用,特别是涉及Lys328的相互作用,是基质特异性的关键决定因素.
- 酶能够稳定各种离子组电荷的能力是其广泛基质接受的基础.
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