单核酸多态驱动的GSTP1酸化和基质相互作用变化的分子动力学研究
Durr-E- Shahwar1, Usama2, Zahid Khan1
1Biochemistry Section, Institute of Chemical Sciences, University of Peshawar, Peshawar, KP, Pakistan.
Journal of biomolecular structure & dynamics
|January 22, 2026
概括
在谷氨S转移酶P1 (GSTP1) 中的Ile105Val替代稍微降低了其对乙烯酸 (EA) 的灵活性和结合亲和力. 这种结构变化会影响排毒和酸化,可能会影响疾病易感性.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 计算生物学 计算生物学
背景情况:
- 谷氨S转移酶 (GSTs) 对于排毒至关重要.
- GSTP1 Ile105Val 多态性 (rs1695) 与酶功能的改变和疾病风险有关.
- 了解这种多态的结构和功能影响是必不可少的.
研究的目的:
- 评估GSTP1Ile105Val替代对蛋白质稳定性,酸化和基质相互作用的影响.
- 调查Val105变体对与乙烯酸 (EA) 的结合亲和力的影响.
主要方法:
- 野生型 (WT) 和Val105突变型GSTP1.1的分子动力学 (MD) 模拟.
- 在GROMACS中利用CHARMM36m力场进行100ns的模拟.
- 使用RMSD,RMSF,Rg,SASA和MM-PBSA进行结构和约束能量分析.
主要成果:
- 无论是WT还是Val105的GSTP1变体,都表现出100ns以上的稳定结构配置文件.
- 值105变种显示了减少波动,并保持了紧性和溶剂暴露.
- 乙酸结合稳定了突变,与WT相比,结合亲和力略有降低,但足够.
结论:
- 在GSTP1中Ile105Val的替代导致微妙的形状变化,降低灵活性和适度降低EA结合亲和力.
- 尽管进行了替代,GSTP1的结构完整性仍保持不变.
- 研究结果表明,有机的基础改变了解毒效率和酸化调节,可能影响疾病易感性.
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