一个结合硫胺的镜像铜中心在一个人造的非血金属酶中
Yoshitsugu Morita1, Hiroki Kubo1, Ryusei Matsumoto1
1Graduate School of Agriculture, Osaka Metropolitan University, 1-1 Gakuen-cho, Naka-ku, Sakai-shi, Osaka 599-8531, Japan.
Journal of inorganic biochemistry
|August 21, 2024
概括
人工金属酶被设计为在催化反应中逆转酶选择性. 铜结合部位的化学修饰成功地将立体化学结果从S型切换到R型.
科学领域:
- 生物化学 生物化学
- 有机化学 有机化学
- 蛋白质工程是指蛋白质工程.
背景情况:
- 人工金属酶结合金属复合物和蛋白质矩阵进行立体选择性催化.
- 工程蛋白质矩阵通过化学修饰和突变性定制器的催化活性.
- 使用了库宾超级家族蛋白质 (TM1459),具有4-His四-金属结合基因.
研究的目的:
- 为了证明人造金属酶的化学修饰,以逆转酶选择性.
- 为了研究固体阻碍对49位的反选择性对固体阻碍的影响.
- 通过调整活性部位的 Re-face 侧面来增强 R-enantioselectivity.
主要方法:
- 通过使用cupin蛋白 (TM1459) 开发出人造非血金属酶.
- 在Si面引入了Cys,并与4,4'-dithiopyridine (4-PDS) 反应形成Cys-4py.
- 产生了各种I49X/H52A/C106D突变,并进行了X射线结晶学.
主要成果:
- 与Cu结合的I49C-4py/H52A/C106D显示了从S-到R-形式的反向酶选择性 (ee = 71%, (R)).
- 在Si面上的4py修饰在逆转enantioselectivity方面最有效.
- 引入H54A突变将R-enantioselectivity提升到88% (ee = 88%, (R)). 在这种情况下,R-enantioselectivity可以提高到88% (ee = 88%, (R)).
结论:
- 人工金属酶的化学修饰可以精确地控制酶选择性.
- 在位置49的绝缘障碍显著影响了立体化学结果.
- 来自X射线晶体学的结构洞察力证实了硫胺结合和活性位点协调.
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