在乙蛋白化酶1中,一个保留但结构分离的循环调节了其催化活性,联体结合和折叠稳定性
William Trey Harris1, Isabelle Altieri1, Isabella Gieck1
1Department of Chemistry and Biochemistry, Butler University, Indianapolis, Indiana, USA.
Proteins
|January 5, 2024
概括
人类乙蛋白雌激酶 (APT) 调节蛋白质膜的定. 人类APT1中的保存循环对于其催化活性,连接物结合和稳定性至关重要,特定的残留物起着关键作用.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 人类乙蛋白雌激酶 (APT) 是一种酶,可以从S-乙化蛋白中去除棕酸盐,控制膜结合.
- 细菌APT同类体中活性部位附近的灵活循环会影响酶构造,但尽管有序列保存,但其在人类APT中的作用尚不清楚.
研究的目的:
- 研究人类APT1 (hAPT1) 中保存循环的功能,调节其催化活性,带结合和蛋白质折叠.
- 为了确定这个循环中的特定残留物,这些残留物对hAPT1的功能和稳定性至关重要.
主要方法:
- 在hAPT1循环中替代关键氨基酸残留的局部定向突变发生.
- 动力测试用于测量催化活性.
- 结构和生物物理特征,包括连接物结合亲和和和蛋白质稳定性测量.
主要成果:
- 尽管与细菌同类相比,hAPT1的保存循环通过影响连接体结合和基质定位来调节催化活动,尽管其结构位置发生了变化.
- 发现特定残留物 (Pro69,Phe72,Asp73,Ile74,Ile75) 对基质选择性,催化和稳定具有重要作用.
- 素71 (Trp71) 对于hAPT1的结构和功能至关重要,其替代导致活动丧失,稳定性降低,并降低了连接体亲和力.
结论:
- 在hAPT1中的分离循环在酶调节,基质相互作用和整体蛋白质稳定性中起着关键作用.
- Trp71代表了α/β水解酶中一种新型的必需酸盐类,以及人类APT中的潜在基位.
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