一个单一的酸盐协调了两种催化步骤
Jian Xie, Timothy Owen1, Ke Xia
1Department of Chemistry, Binghamton University, State University of New York , 4400 Vestal Parkway East, Binghamton, New York 13902, United States.
Journal of the American Chemical Society
|August 17, 2016
概括
一个关键的酸盐残留物 (D46) 在 (Hh) 中信号蛋白自处理对于胆固醇修饰至关重要. 这种残留物结合了两个催化步骤,确保有效的Hh信号通路激活.
科学领域:
- 生物化学
- 分子生物学
- 细胞信号传输
背景情况:
- 刺 (Hh) 信号由胆固醇修饰的Hh连接体启动.
- Hh联体生成涉及Hh前体蛋白的自处理.
- 有效的Hh信号需要合N-S乙烯转移和转化步骤进行胆固醇化.
研究的目的:
- 调查一个保存的酸盐残留物 (D46) 在Hh自处理领域的作用.
- 阐明D46协调Hh自处理和胆固醇化的催化步骤的机制.
主要方法:
- 在Hh前体蛋白中对D46残留物的局部定向突变.
- 核磁共振 (NMR) 光谱测定D46的pKa.
- 测量Hh胆固醇和自动处理效率.
主要成果:
- 突变性显示D46抑制非本源自动处理,对胆固醇转化至关重要.
- 核磁共振数据显示D46由于与催化剂半氨酸结合而增加了pKa (5.6).
- 一个D46N突变取消了Hh胆固醇化,这表明了D46的质子化和脱质子化形式的重要性.
结论:
- 酸盐残留物D46作为Hh自处理的关键协调者.
- D46的质子穿机制机械地连接了N-S转移和转化步骤.
- 这种D46的协调对于Hh胆固醇和随后的信号转导至关重要.
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