结构不同的N-和O-甲基转移酶之间的融合机制特征:甘氨酸N-甲基转移酶和甲基转移酶
Jianyu Zhang1, Judith P Klinman1
1Department of Chemistry, ‡Department of Molecular and Cell Biology, and §California Institute for Quantitative Biosciences, University of California , Berkeley, California 94720, United States.
Journal of the American Chemical Society
|June 30, 2016
概括
甘氨酸N-甲基转移酶 (GNMT) 使用蛋白质结构来促进甲基转移. 一个氨酸残留是关键,减少捐赠者-接受者距离以实现有效的催化,类似于其他甲基转移酶.
科学领域:
- 生物化学
- 酵素学
- 蛋白质的结构和功能
背景情况:
- 甲基转移酶是具有不同生物作用的关键酶.
- 对甲基转移机制的全面理解仍然不完整.
- 用S-adenosyl-l-methionine (AdoMet) 甲基化甘氨酸N-甲基转移酶 (GNMT).
研究的目的:
- 调查GNMT的甲基转移机制.
- 探索蛋白质结构在酶催化中的作用.
- 将GNMT与其他甲基转移酶,如甲基醇转移酶进行比较.
主要方法:
- 对野生型GNMT和Tyr21突变物进行了初级和二级动态同位素效应测量.
- 分析了碳-12/14和-1/3的动态同位素效应.
- 确定了野生型GNMT和突变的结合同位素效应.
主要成果:
- 动态同位素效应数据表明在甲基转移过程中蛋白质结构诱导的紧缩.
- 在GNMT和Catechol O-methyltransferase之间观察到具有显著的催化特性.
- 一个位于AdoMet甲硫后面的氨酸侧链被确定为催化剂的关键.
结论:
- 蛋白质结构在促进GNMT中的甲基转移步骤中起着至关重要的作用.
- 根据氨酸残留物,建议减少甲基供体-接受体距离.
- 甲基转移酶中的酶结构-功能关系可以表现出尽管有不同的活性位点,但仍具有保留的机制.
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