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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2023, Vol. 43 Issue (10): 43-51    DOI: 10.13523/j.cb.2304037
综述     
代谢物衍生的非酶促翻译后修饰研究进展*
董媛媛,鲍秋雨,王德祥,温宏涛,杨行超,皖宁**(),叶慧**()
中国药科大学药物代谢动力学重点实验室 南京 210009
Advance in Metabolite-mediated Non-enzymatic Post-translational Modifications
DONG Yuan-yuan,BAO Qiu-yu,WANG De-xiang,WEN Hong-tao,YANG Xing-chao,WAN Ning**(),YE Hui**()
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China
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摘要：

代谢物在细胞生命周期中具有重要作用,包括为细胞生命活动提供能量及合成原料、参与生物信号转导等。已有研究表明,活性代谢物可通过体内自发化学反应共价修饰蛋白,调控蛋白质结构和功能,进而影响细胞生命活动的各个环节。近年来,发展迅速的蛋白质组学技术能够捕获这类非酶促修饰的靶蛋白,继而阐明代谢物对靶蛋白功能的调控机制。由活性代谢物产生的非酶促共价修饰,分为可逆和不可逆两种类型。详细介绍代谢物衍生的非酶促翻译后修饰的形成机理,并列举蛋白质组学技术如何鉴定这类修饰进而揭示代谢调控机制的经典研究案例。
关键词： 活性代谢物;  非酶促共价修饰;  蛋白组学技术    
Abstract:

Endogenous small molecules play vital roles in the cell lifespan, such as supplying the energy and substrates for biological processes and mediating cellular communication. Previous studies have shown that some endogenous reactive molecules can non-enzymatically modify proteins via spontaneous chemical reactions, thereby regulating protein structure and functions and participating in various cellular processes. Recently, the rapid development of proteomics technology for capturing non-enzymatically modified target proteins contributes to elucidating the function of the modified target protein. This review focuses on reversible and irreversible non-enzymatic covalent modifications (NECMs) produced by active metabolites, respectively, and introduces the formation mechanism of NECMs and the application of proteomics in the discovery of new post-translational modifications (PTMs) and the elucidation of metabolites-regulated protein functions.
Key words: Reactive metabolite    Non-enzymatic covalent modifications    Proteomics
收稿日期: 2023-04-18 出版日期: 2023-11-02
ZTFLH:  Q816  
基金资助: *国家自然科学基金(82173783);江苏省自然科学基金杰出青年基金(BK20220088)
通讯作者: **电子信箱:wan_ning95@126.com;cpuyehui@cpu.edu.cn   
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董媛媛
鲍秋雨
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温宏涛
杨行超
皖宁
叶慧

引用本文:

董媛媛, 鲍秋雨, 王德祥, 温宏涛, 杨行超, 皖宁, 叶慧. 代谢物衍生的非酶促翻译后修饰研究进展*[J]. 中国生物工程杂志, 2023, 43(10): 43-51.

DONG Yuan-yuan, BAO Qiu-yu, WANG De-xiang, WEN Hong-tao, YANG Xing-chao, WAN Ning, YE Hui. Advance in Metabolite-mediated Non-enzymatic Post-translational Modifications. China Biotechnology, 2023, 43(10): 43-51.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2304037    或    https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I10/43

图1  LDEs结构式及羰基化反应
图2  基于ABPP技术发现PTMs靶蛋白
图3  糖化反应
图4  琥珀酸化反应
图5  酰化反应
图6  LGSH介导的非酶促乳酰化反应
图7  多磷酸化及焦磷酸化反应
修饰类型 修饰名称 代谢物 修饰的位点 参考文献
不可逆的NECMs 羰基化修饰 脂质过氧化产物 半胱氨酸、赖氨酸和组氨酸 [11-12]
糖化修饰 糖类及糖的衍生物 赖氨酸、精氨酸 [15-16]
琥珀酸化修饰 琥珀酸 半胱氨酸 [22]
可逆的NECMs 乙酰化修饰 乙酰辅酶A、酰基磷酸酯 赖氨酸、半胱氨酸 [30]
琥珀酰化修饰 琥珀酰辅酶A 赖氨酸 [33]
其他酰化修饰 代谢物酰基辅酶A 赖氨酸 [34?-36]
乳酰化修饰 乳酰化谷胱甘肽 赖氨酸 [37]
多磷酸化修饰 多聚磷酸盐 赖氨酸 [40]
焦磷酸化修饰 二磷酸肌醇聚磷酸盐 磷酸化的丝氨酸 [4,41]
表1  代谢物衍生的非酶促共价修饰
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