人类3'-adenosine 5'-phosphosulfate合成酶 (hPAPSS) 的ATP硫酶域的结构/功能
K V Venkatachalam1,2, Dhiraj Sinha3, Chris Soha2
1College of Allopathic Medicine, USA.
Biochemistry and biophysics reports
|January 6, 2025
概括
这项研究确定了H425NGH428图案.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 分子生物学分子生物学
背景情况:
- 3'-adenosine 5'-phosphosulfate (PAPS) 对于硫化反应至关重要.
- PAPS合成酶 (PAPSS) 在两个步骤中催化PAPS合成:ATP硫化酶 (ATPS) 和APS-激酶 (APSK).
- 人类PAPSS1 (hPAPSS1) 异型具有不同的N端APSK和C端ATPS域.
研究的目的:
- 研究H425NGH428基因在hPAPSS1的ATPS活性中的功能作用.
- 描述一种新的hPAPSS1突变 (N426K) 的动力特性.
- 阐明全长hPAPSS1及其个别域之间的动态差异.
主要方法:
- 局部定向的突变发生,以产生hPAPSS1变种.
- 对ATP和硫酸盐的酶动力学测定 (Km,Vmax).
- 在基中进行ATP结合和分子动力学模拟.
- 对全长酶和域删除突变的分析.
主要成果:
- H425NGH428基因对hPAPSS1的ATPS活性至关重要,正如结合研究所显示的那样.
- 与野生型相比,N426K突变体显示了ATP和硫酸盐的显著增强的催化效率 (Vmax/Km).
- 全长的hPAPSS1表现出与ATP的双模动力学,仅在C端ATPS域中丢失,表明域间影响.
结论:
- H425NGH428基因对hPAPSS1.1.的ATP硫化酶功能至关重要.
- 将N426转变为K可以提高hPAPSS1.1的催化效率.
- 在hPAPSS1中ATPS和APSK域的融合性质导致独特的结构和运动性质,与单个域不同.
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