核酸与无氧核酸还原酶中的ATP结合的核酸通过调节基质结合来全osterically调节活性
Ornella Bimai1, Ipsita Banerjee2, Inna Rozman Grinberg1
1Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden.
eLife
|July 5, 2024
概括
脱氧腺三酸盐 (dATP) 通过增加关键域的灵活性,防止基质结合和酶活性来抑制无氧核酸减少酶 (RNR). 这项研究揭示了厌氧RNR的机制,与之前研究的有氧形式不同.
科学领域:
- 生物化学 生物化学
- 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 (RNR) 是DNA合成的必需酶,由核酸结合域调节.
- 有氧RNR的特征很好,具有涉及寡合化的脱氧腺三酸盐 (dATP) 抑制机制.
- 无氧RNRs的dATP抑制机制仍然未知,尽管它们具有独特的结构特征,如稳定的糖基基域 (GRD).
研究的目的:
- 阐明ATP和dATP与Prevotella copri*的无氧RNR结合的生物化学,生物物理和结构基础.
- 了解无氧RNR中dATP依赖抑制的机制.
主要方法:
- 生物化学测试用于测量酶活性.
- 生物物理技术研究蛋白质动力学和寡合化.
- 电子显微镜 (cryo-EM) 用于结构的确定.
主要成果:
- ATP结合有利于二次状态和具有有序GRD的活性酶.
- dATP结合将平衡转移到四重体状态,使酶失活,并增加GRD的灵活性,防止基质结合.
- 低温-EM结构揭示了一个涉及GRD,基质特异性部位和活性部位的调节网络,dATP诱导远离结合部位的形状变化.
结论:
- dATP通过破坏GRD和活性部位来抑制无氧P.copri*NrdD,阻碍基质的进入和激进的动员.
- 这种机制与有氧RNR不同,突出了无氧酶中独特的调节策略.
- 这些发现为无氧生物体中DNA合成前体的调节提供了关键的见解.
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