通过HppE进行激素介导催化的证据:一项使用环烯和甲基环烯基基底相似物的研究
Hui Huang1, Wei-chen Chang, Pei-Jing Pai
1Division of Medicinal Chemistry, College of Pharmacy, and Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, USA.
Journal of the American Chemical Society
|September 26, 2012
概括
(S) - 2 - 基酸氧化酶 (HppE) 使用激素中间体进行菌素生物合成. 研究显示,在 (R) -HPP氧化中存在一个以C2为中心的基,为这种不寻常的铁酶提供了关键的机理洞察力.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 有机化学 有机化学
背景情况:
- 酶 (S) -2-基酸氧化酶 (HppE) 对于菌素抗生素生物合成至关重要.
- HppE是一种不寻常的单核铁酶,可催化 (S) - 2 - 基酸 ((S) - HPP) 的氧化环氧化.
- 此外,HppE还将 (R) - 异构体 (R) - 2 - 基基酸 (R) - HPP) 加工成2 - 基基酸.
研究的目的:
- 阐明HppE催化氧化反应的反应机制.
- 调查激进中间体在HppE活动中的参与.
- 探测HppE的基质特异性和催化途径.
主要方法:
- 合成含有环烯和甲环烯的激素时钟基板类似物.
- 使用这些类似物进行酶分析以研究HppE活性.
- 对反应产物的分析,以确定酶机制.
主要成果:
- HppE有效地将含有环烯的类似物转化为环氧化物 ((S) - 异构体) 和子 ((R) - 异构体) 产品.
- 甲基烯cyclopropyl类似物迅速无活化HppE,表明一个快速的激素触发的环开放.
- 实验证据支持在 (R) -HPP氧化中具有纳秒寿命的C2-中心的基质中间体.
结论:
- 这项研究提供了第一个实验证据,证明在HppE催化 (R) -HPP氧化过程中,存在C2中心的中间基.
- 激进时钟类似物有效地探测HppE不寻常的酶反应的机制.
- 这些发现有助于我们更好地了解单核铁酶催化和胺酸生物合成.
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