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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
乙醇胺氨基酶自杀失活的不同机制
Gregory M Sandala1, David M Smith, Leo Radom
1School of Chemistry, University of Sydney, Sydney, NSW 2006, Australia.
Journal of the American Chemical Society
|June 16, 2005
概括
基质类似物可以通过停止酶功能来抑制乙醇胺氨基酶 (EAL). 计算研究揭示了不同的无活化机制,涉及稳定基和内热步骤,特别是对糖类甲和2-乙烯.
科学领域:
- 生物化学 生物化学
- 计算化学的计算化学
- 酶学 是一种酶学.
背景情况:
- 乙醇胺氨酶 (EAL) 是代谢途径中的关键酶.
- 了解酶失活机制对于药物开发和生物催化剂至关重要.
- 基质类似物经常用于探测酶机制并识别潜在的抑制剂.
研究的目的:
- 通过使用三种不同的基质类似物来研究EAL自杀性失活的机制.
- 阐明拟议的失活路径的计算能量学.
- 为了比较糖类甲,2-基乙基 (HEH) 和2-氨基乙甲的失活机制.
主要方法:
- 最初的分子轨道计算被用来研究反应途径.
- 对过渡状态和中间体进行分析,以确定反应能量.
- 计算的能量与实验观测的比较.
主要成果:
- 预计2-氨基乙醇的正常催化机制是外热的.
- 葡萄糖和HEH通过涉及高度稳定基和内热再抽象步骤的途径诱导无活化.
- 2-氨基乙甲基表现出不同的无活化机制,其中一条通路导致酸和氨基离子的形成,再生了激进的辅因子.
结论:
- 通过基质类似物对EAL的自杀性无活化通过不同的机制发生.
- 稳定基和内热性步骤是糖醇和HEH无活化的关键特征.
- 2-氨基乙甲的失活机制有显著差异,涉及辅因子再生,但随后的降解途径尚未完全阐明.
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