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基于ADP-ribosyltransferase的非水解NAD+类型的生物催化

Moona Sakari¹, Rajendra Bhadane¹, Sujit Kumar¹

¹Institute of Biomedicine, University of Turku, Turku, Finland.

The Journal of biological chemistry

|December 20, 2024

概括

这项研究详细介绍了一种新的生物催化方法,使用百日咳毒素来制造不可水解的NAD+类似物. 这些新型化合物,包括光版本,是研究参与ADP-ribosylation和药物开发的酶的宝贵工具.

科学领域:

生物化学生物化学
酶学是一种酶学.
化学生物学化学生物学

背景情况:

酶杂乱使得无意反应的催化成为可能.
尼古丁胺胺氨基二核酸 (NAD+) 类似物是生物化学研究中的关键工具.
百日咳毒素的S1亚单元 (PtxS1) 具有ADP-ribosyltransferase活性.

研究的目的:

开发一种生物催化工艺,用于合成不可水解的NAD+类似物.
为了利用 PtxS1 的乱交活动来产生新的化合物.
创建用于研究NAD+依赖酶和推进药物发现的工具.

主要方法:

利用PtxS1的ADP-ribosyltransferase活性与尼古丁胺胺类同类物发生反应.
使用PtxS1与NAD+和3-aminobenzamide (3-AB) 联合结晶的结构数据.
使用基于药的选和量子力学模拟来识别反应性类似物.
通过高性能液态染色学 (HPLC) 和质谱学确认产品形成并识别新实体.

主要成果:

建立了一种生物催化方法,以产生不可水解的NAD+类型.
合成了胺氨基氨酸二核酸,证实了PtxS1与修饰基质的活性.
确定了两种新的NAD+类型,即isoindolone amin adenine dinucleotide和isoquinolinone amine adenine dinucleotide,这两种新型的NAD+类型.
发现异华诺氨基氨基氨基二核酸具有高度的光.

结论:

可以通过PtxS1的工程设计,通过酶杂交产生新的非水解NAD+类型.
新合成的NAD+类似物对NAD+结合酶的结构和酶学研究非常有价值.
这些类似物具有促进药物开发的潜力,这些药物可以向聚基聚合酶和细菌毒素等酶.

关键词:

它们是ADP-ribosyl转移酶.它们是NAD+NAD+NAD.生物催化剂的生物催化剂酶杂乱性酶杂乱性是一种核酸类比的核酸类比

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