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鉴定SIRT3作为H4K16la的擦拭剂

Zhuming Fan^1,2,3, Zhiyang Liu⁴, Nan Zhang³

¹Institute of High Energy Physics, CAS, Beijing 100000, China.

|September 18, 2023

概括

氨酸乳酸化 (Kla) 是一种新的修改. SIRT3表现出强烈的Kla擦拭剂活性,并开发了化学探针来研究这一过程及其在基因调节中的作用.

科学领域:

生物化学生物化学
分子生物学分子生物学
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

氨酸乳酸化 (Kla) 是一种最近发现的基因素修饰.
基因组脱乙酶 (HDACs) 和Sirtuins是已知的Kla擦除剂,但效率和机制各不相同.

研究的目的:

调查Sirtuins,特别是SIRT3.3的Kla擦拭剂活性.
为了阐明SIRT3与乳酸lysine的结合机制.
开发化学探测器,用于研究Kla擦拭剂活性和脱乳化过程.

主要方法:

酶活性测定比较SIRT3与其他Sirtuins对H4K16la.
进行X射线晶体学,以确定SIRT3与乳酸lysine的结合结构.
开发和应用化学探针 (p-H4K16laAlk和p-H4K16la-NBD) 来捕获目标和检测光.

主要成果:

在H4K16la部位上,SIRT3表现出显著的Kla擦拭剂活性,超过了其他人类Sirtuins.
晶体结构为SIRT3和乳酸lysine之间的结合相互作用提供了详细的见解.
蛋白质组分析证实SIRT3被p-H4K16laAlk探针捕获.
该p-H4K16la-NBD探针使得基于光的直接检测可实现.

结论:

SIRT3 是 H4K16.16 处氨酸乳酸化的强有力的擦除剂.
结构数据揭示了SIRT3介导的脱甲基化的分子基础.
新的化学探测器有助于研究Kla擦拭剂及其在基因转录中的作用.

关键词:

酶学是一种酶学.分子相互作用分子相互作用.蛋白质蛋白质是一种蛋白质.结构生物学是结构生物学.

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