对甲和烯单氧基酶氧酶的不同二氧化物激活路径的洞察
Arteum D Bochevarov1, Jianing Li, Woon Ju Song
1Department of Chemistry, Columbia University, New York, New York 10027, USA.
Journal of the American Chemical Society
|April 27, 2011
概括
甲和二烯单氧化酶具有相似的活性位点,但具有不同的中间特性. 结构上的差异,特别是氨酸残留物的配置,解释了这些变化,并影响了酶的功能.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 结构生物学 结构生物学
背景情况:
- 甲单氧化酶 (MMOH) 和烯单氧化酶 (TMOH) 具有非常相似的活性位点.
- 尽管结构相似,但它们的氧化中间体表现出不同的物理和化学性质.
- 了解这些差异对于阐明酶机制和设计新型生物催化剂至关重要.
研究的目的:
- 为了比较MMOH和TMOH的活跃地点附近的结构差异.
- 研究特定残留物的作用,如氨酸,在氧化中间体的不同行为中.
- 提出一个假设,解释MMOH和TMOH中不同的过氧二铁 (III) 物种的形成.
主要方法:
- 分析多重晶体结构以确定结构变异.
- 分子力学 (MM) 和量子力学/分子力学 (QM/MM) 计算方法用于研究残留旋转能量概况.
- 对于过氧二铁 (III) 模型的Mössbauer光谱的理论计算.
主要成果:
- 在活性部位附近确定了氨酸残留物的不同旋转配置 (MMOH中的T213,TMOH中的T201).
- 建议这些氨酸残留物会影响不同类型的过氧二铁的形成.
- QM/MM计算和Mössbauer光谱支持了这一假设,并解释了中间行为,包括T201S突变物.
结论:
- 氨酸残留物的独特旋转配置是MMOH和TMOH中观察到的不同中间体性质的关键.
- ToMOD调节蛋白可能在中间体的形成和酶的功能中起着重要作用.
- 氧部分的质子化,可能被T201稳定,解释了ToMOH (氧) 中介的低四极分裂.
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