细胞染色体p450芳酶的最终催化步骤:密度功能理论研究研究
John C Hackett1, Robert W Brueggemeier, Christopher M Hadad
1Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, Ohio 43210, USA. hackett.35@osu.edu
Journal of the American Chemical Society
|April 7, 2005
概括
芳香酶是一种芳香酶.
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:
- 芳酶对于雌激素生物合成至关重要.
- 它最后的催化步骤的精确机制仍然不完全理解.
- 之前的研究提出了各种中间体和途径.
研究的目的:
- 阐明芳酶作用中的第三个催化步骤的机制.
- 研究特定中间体和反应途径的作用.
- 确定拟议机制的能源可行性.
主要方法:
- B3LYP密度函数理论计算.
- 一开始的分子动力学模拟.
- 过渡状态和反应障碍的分析.
主要成果:
- 过氧乙中介的质子辅助同解在能量上是有利的.
- 通过P450化合物I从化基质中提取1β-原子的速度明显更快.
- 芳酶表现出脱酶的行为,涉及抽象和gem-diol脱.
结论:
- 减少的铁氧二氧化物中间体不太可能调解雄激素芳香化.
- 最后的催化步骤涉及从化基质中抽取1β-原子,然后进行gem-diol脱质.
- 芳酶在其终端催化步骤中作为脱酶起作用.
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