氧化物合成酶中的结合基质是质子化还是中性化,以及执行基质氧化的活性氧化剂是什么?
Sam P de Visser1, Lee Siew Tan
1Manchester Interdisciplinary Biocenter and the School of Chemical Engineering and Analytical Science, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, United Kingdom. sam.devisser@manchester.ac.uk
Journal of the American Chemical Society
|September 9, 2008
概括
密度函数理论研究揭示了氧化合成酶 (NOS) 酶通过一种新的途径氧化L-氨酸. 化合物II是关键的氧化剂,与细胞染色体P450机制不同.
科学领域:
- 生物化学和酶学 生物化学和酶学
- 计算化学是一种计算化学.
- 机械酶学 机械酶学
背景情况:
- 氧化合成酶 (NOS) 酶催化L-氨酸的氧化成N(omega) -氧氨酸.
- 据说NOS的催化机制类似于P450酶的催化机制.
- 了解NOS催化循环中的精确步骤对于阐明酶功能至关重要.
研究的目的:
- 通过密度函数理论 (DFT) 研究氧化合成酶 (NOS) 催化循环中的关键步骤.
- 通过NOS阐明L-氨酸氧化L-氨酸的机制.
- 为了将NOS机制与细胞P450酶的机制进行比较.
主要方法:
- 密度功能理论 (DFT) 的计算是在NOS.的酶活性部位模型上进行的.
- 对反应路径,过渡状态和中间能量的分析.
- 研究了质子转移机制和电子结构.
主要成果:
- 确定了L-氨酸氧化的一种低能耗途径,与细胞染色体P450.0不同.
- 基质L-氨酸作为一个质子捐赠体和基化物种.
- 化合物II是活性铁物种的减少形式,被确定为NOS的主要氧化剂,与P450不同,它是一种缓慢的氧化剂.
结论:
- NOS酶采用独特的催化机制来氧化氨酸,其中化合物II作为活性氧化剂.
- 拟议的机制涉及从氨酸到化合物I的初始电子转移,形成化合物II,随后是抽象和基因重组.
- 蛋白质的环境影响对反应机制能量的影响最小.
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