利用辅因子结合能用于酶催化:形成整个NAD辅因子和辅因子部分的脱酶催化反应
Judith R Cristobal1, Richard W Nagorski2, John P Richard1
1Department of Chemistry, University at Buffalo, SUNY, Buffalo, New York 14260-3000, United States.
Biochemistry
|July 18, 2023
概括
酶催化被诱导适合机制优化. 结合NAD辅因子碎片与Candida boidinii形成脱酶 (CbFDH) 激活化物转移,证明基于碎片的酶激活.
科学领域:
- 生物化学 生物化学
- 酶动力学 酶动力学
- 蛋白质的结构变化.
背景情况:
- 酶催化是由诱导适合机制驱动的,其中基质结合优化蛋白质结构以加速.
- NAD辅因子在酶反应中起着至关重要的作用,特别是在化物转移过程中.
研究的目的:
- 测试假设NAD的腺5'-二酸盐核糖 (ADP-核糖) 片段激活Candida boidinii形成脱酶 (CbFDH).
- 调查辅助因子碎片结合能在驱动蛋白质结构变化的作用,以促进催化.
主要方法:
- 酶分析测量化物转移速率.
- 确定配因子碎片的结合亲和和和过渡状态稳定能量的确定.
主要成果:
- ADP-ribose片段稳定了CbFDH催化化物转移的过渡状态>14 kcal/mol.
- ADP,AMP和核糖5'-酸盐碎片也激活了CbFDH,使过渡状态稳定了4.4-5.5kcal/mol.
- 建议激活涉及R174和激活剂酸盐离子之间的离子对相互作用.
结论:
- 共因子碎片可以通过诱导具有催化作用的相关形状变化来激活酶.
- 基于碎片的激活机制为酶的进化和设计提供了洞察力.
- 这项研究强调了特定相互作用在稳定酶结合过渡状态方面的重要性.
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