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通过HisAT/NAT16合成乙希斯提丁的分子基础

Matti Myllykoski¹, Malin Lundekvam², Camilla Osberg²

¹Department of Biomedicine, University of Bergen, Bergen, Norway. matti.myllykoski@uib.no.

Nature communications

|July 2, 2025

概括

研究人员确定NAT16是负责人体乙基化酶 (HisAT) 生产人体乙基化的酶. 一种常见的变种会影响酶功能,通过改变血中乙希斯提丁水平,可能会影响病风险.

科学领域:

生物化学生物化学
分子生物学分子生物学
人体生理学人体生理学

背景情况:

乙希斯提丁存在于人体血液中,但其来源和作用尚不清楚.
乙希斯提丁通过将乙基从乙-CoA转移到希斯提丁来合成.
一种特定的NAT16变体 (p.Phe63Ser) 与较低的乙基胺水平和病风险增加有关.

研究的目的:

为了确定对人类的胺乙化负责的酶.
调查NAT16变种,乙西斯蒂丁水平和病之间的关联的生物化学基础.

主要方法:

在体外和体内生化分析以表征酶活性.
希斯蒂丁乙转移酶 (HisAT) 的结构分析.
对NAT16变种的种群遗传学分析.

主要成果:

细胞内酶NAT16被确定为人类的胺乙转移酶 (HisAT).
该NAT16变体 (p.Phe63Ser) 呈现出对histidine的 afinity 降低,导致acetylhistidine催化作用降低.
他的AT具有独特的双Gcn5相关的N-乙转移酶 (GNAT) 折叠,在各种生物体中保存.

结论:

NAT16是人类主要的胺乙转移酶,采用独特的结构折叠.
常见的NAT16变种损害了乙西斯提丁合成,可能会影响血水平和脏健康.
了解HisAT的结构和功能,可以了解新陈代谢调节和疾病相关性.

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