单甲基素与Zn2+在葡萄糖皮质类受体的结合部位上竞争
Anne M Spuches1, Dean E Wilcox
1Department of Chemistry, Dartmouth College, Hanover, New Hampshire 03755, USA.
单甲基化 (MMAIII),与化不同,将离子从葡萄糖皮质体受体DNA结合域 (GR-DBD) 中取代. 这种干扰会损害受体结合DNA的能力,影响基因调节.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 毒理学 毒理学 毒理学
背景情况:
- 葡萄糖皮质体受体 (GR) 在基因调节中起着至关重要的作用.
- DNA结合域 (GR-DBD) 需要两个Zn2+离子来实现结构完整性和DNA结合.
- 类物质,如矿和单甲基矿,是已知的环境毒素,可以干扰细胞过程.
研究的目的:
- 研究矿 (As(III)) 和单甲基矿 (MMAIII) 与GR-DBD的相互作用.
- 为了确定这些素是否与GR-DBD中必不可少的Zn2+离子竞争.
- 评估结对GR-DBDDNA结合能力的影响.
主要方法:
- 异热定位热量计 (ITC) 用于研究结合热力学.
- 循环二重化 (CD) 光谱法用于监测结构变化和Zn2+位移.
- 进行了Zn2+结合的GR-DBD与酸盐和MMAIII的定位.
主要成果:
- 异热定位热量计揭示了酸盐和MMAIII的明显的结合热力学.
- 发现MMAIII,但不是化,与GR-DBD中的至少一个Zn2+离子竞争并取代它.
- 循环二元论证实,只有MMAIII破坏了GR-DBD的Zn2+稳定二次结构.
结论:
- 单甲基化 (MMAIII) 可以从GR-DBD中取代离子,与化不同.
- 由MMAIII取代Zn2+导致GR-DBD的结构完整性丧失.
- 这种干扰损害了GR-DBD结合DNA的能力,可能会影响葡萄糖皮质激素介导的基因表达.
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