乙-CoA合成酶的活性通过使用乙-CoA或乙酸作为捐赠分子的lysine乙化进行酶调节
Chuan Qin1, Leonie G Graf1, Kilian Striska1
1Department of Synthetic and Structural Biochemistry, Institute of Biochemistry, University of Greifswald, 17489, Greifswald, Germany.
Nature communications
|July 17, 2024
概括
素乙化调节了乙-CoA合成酶的作用. 细菌细菌AcuA酶乙化AcsA,导致复杂的解离和调节活性通过透乙酶的功能.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 酵素法规 酵素法规
背景情况:
- 氨酸乙化是AMP形成的乙-CoA合成酶 (AcsA) 在细菌和真核生物中的关键调节机制.
- 控制这种调节的精确分子机制,特别是乙转移酶和合成酶之间的相互作用,仍然在很大程度上未被阐明.
研究的目的:
- 阐明Bacillus subtilis乙转移酶AcuA通过lysine乙化调节AMP形成的乙-CoA合成酶AcsA的机制.
- 为了研究AcuA介导的AcsA乙化的结构和功能后果.
- 在AcuA-AcsA复合体内发现新的酶活性.
主要方法:
- 生物化学试验用于研究AcuA•AcsA复合物的形成,解离和乙化.
- 使用x射线晶体学分析AcsA在apo和乙-AMP结合状态中的结构分析.
- 使用AlphaFold2进行计算建模,以预测复杂结构和结构变化.
- 酶活性测定用于表征酸酶活性.
主要成果:
- 这种AcuA•AcsA复合物在AcuA调节的AcsA lysine乙化时分离,依赖于乙-辅酶A (乙-CoA).
- 晶体结构揭示了AcsA的灵活C端域采用了不同的构造,AlphaFold2表明AcuA结合稳定了新的AcsA构造.
- AcuA•AcsA表现出内在的透乙酶活性,从乙酸 (AcP) 和辅酶A (CoA) 中产生乙-CoA.
结论:
- 这项研究提供了关于AMP形成的乙-CoA合成酶的依赖于 lysine 乙化调节的机制性见解.
- 在AcuA•AcsA复合体中发现了一种内在的甲酸酶活性,可以根据AcP和CoA的可用性调节AcsA的活动.
- 这种双重功能凸显了一个复杂的监管网络,控制乙-甲酸代谢.
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