如何ATP和dATP重新定位III类核糖核酸还原酶域以调节酶活性?
Gisele A Andree1, Kelsey R Miller-Brown2,3, Zhuangyu Zhao2
1Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science advances
|November 28, 2025
概括
第三类核糖核酸还原酶 (RNR) 使用不同的构造来调节活性. ATP 结合将一个活动部位的置为活动部位,而 dATP 结合将其移开,控制基质的访问.
科学领域:
- 生物化学 生化学
- 结构生物学 结构生物学
- 酶学 是一种酶学.
背景情况:
- рибо核酸减少酶 (RNRs) 是必要的酶,可以将 рибо核酸转化为脱氧核酸.
- RNR活性通常由细胞dATP/ATP比率调节,影响酶功能.
研究的目的:
- 为了研究无氧,III类RNRs的全调节.
- 确定在*Streptococcus thermophilus* NrdD (StNrdD) 中通过ATP和dATP进行差异调节的结构基础.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定StNrdD结构.
- -交换质谱 (HDX-MS) 用于验证结构发现.
- 位点定向突变发生以探测功能机制.
主要成果:
- 在结合ATP (激活剂) 与dATP (抑制剂) 时,StNrdD表现出不同的"形"域构造.
- ATP结合将"活性部位"定位到活性部位,可能促进基质结合.
- dATP结合将"活性部位"移开,这表明通过改变基质访问而不是通过激素转移调制来抑制.
结论:
- 第三类RNR监管涉及监管领域的结构变化,影响基质结合.
- 活性部位的差异定位是通过ATP和dATP进行全性控制的关键.
- 结构洞察力揭示了由核酸结合驱动的差异域构造的基础分子机制.
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