关于蛋白酶催化在气相,溶液和弹性酶中的脱氧化步骤的理论研究
1Physical and Theoretical Chemistry Laboratory, University of Oxford, South Parks Road, OX1 3QZ, United Kingdom. maya@salliab.org
Journal of the American Chemical Society
|November 4, 2004
概括
血清蛋白酶催化解离析是酶中的一个阶段性反应,与气相不同. 四面体中间体由酶静电学稳定,使其成为速度决定的步骤.
科学领域:
- 生物化学 生物化学
- 计算化学计算化学
- 酶学 是一种酶学.
背景情况:
- 血清蛋白酶是参与各种生物过程的关键酶.
- 了解催化机制,特别是脱,是酶功能的关键.
- 之前的研究已经提出了蛋白酶催化过程的不同机制.
研究的目的:
- 为了阐明血清蛋白酶的脱氧化机制.
- 研究溶剂和酶环境在反应途径中的作用.
- 为了确定催化步骤的能量概况.
主要方法:
- 密度函数理论 (DFT) 的计算.
- 最初的量子力学/分子力学 (QM/MM) 计算.
- 分子动力学 (MD) 和采样模拟.
主要成果:
- 脱机制从在气相中的协调转移到使用溶剂或酶的逐步转移.
- 在酶中形成一个稳定的四面体中间体,通过静电相互作用稳定.
- 形成中间体的第一步是以比水低的激活能量确定速率.
- 后续步骤涉及由于侧链移动和相关的结合部位重排的小障碍.
结论:
- 酶环境显著改变了血清蛋白酶脱氧化机制.
- 静电相互作用,特别是氧离子孔和Asp102,稳定了四面体中间体.
- 建议产品释放与脱过程相结合.
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