人类蒂胺DNA糖酶的特异性取决于N-糖酸结合的稳定性
Matthew T Bennett1, M T Rodgers, Alexander S Hebert
1Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Journal of the American Chemical Society
|September 21, 2006
概括
人类胆氨酸DNA糖酶 (hTDG) 通过利用基糖键稳定性的差异来歧视细胞氨酸. 它的特异性取决于离开群体的能力和活跃的网站互动,而不是排斥.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 通过切除受损的基,DNA糖基酶启动DNA基切除修复.
- 人类胆氨酸DNA糖酶 (hTDG) 修复GT不对,但避免了丰富的GC对.
- 在HTDG的特异性背后的机制,特别是它避免细胞因子的机制,尚不清楚.
研究的目的:
- 为了研究在hTDG的基质特异性中,切片基糖结合稳定的作用.
- 为了确定离开组的能力和活性位点相互作用是否支配hTDG对细胞素的歧视.
主要方法:
- 测量了hTDG对不同核基的最大活性 (k(max)).具有不同的离开组能力.
- 分析了k ((max) 与离开组pK ((a) 之间的关系,以确定反应机制.
- 评估了HTDG活性部位的疏水性对基质歧视的贡献.
主要成果:
- 与 uracil 和 thymine 相比,hTDG 对5-fluorouracil 和 5-chlorouracil 的活性显著更高,与离开组的能力相关.
- hTDG很容易切除具有改进的离开组的细胞因子类似物,表明细胞因子可以进入活性部位.
- 一个线性自由能量关系证明了一个高度分离的反应机制,斜率 (βlg) 为-1.6 ± 0.2.2.
- hTDG的疏水活性位点放大了固有的基质反应率差异.
结论:
- hTDG的特异性主要取决于N-糖基键的稳定性,特别是基的离开组的能力.
- 对细胞氨酸的歧视主要是由于其离开能力不佳,而不是它被排除在活性部位之外.
- 酶的活性部位结构通过利用这些化学差异来增强特异性.
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