Nucleophilic Thiol Proteins Bind Covalently to Abasic Sites in DNA
Nucleophilic Thiol Proteins Bind Covalently to Abasic Sites in DNA
复制标题
DOI：
10.1021/acs.chemrestox.2c00068
复制
发表时间：
2022-04-28
影响因子：
4.1
通讯作者：
Guengerich, F. Peter
中科院分区：
文献类型：
--
作者：
Ghodke, Pratibha P.;Matse, Johannes H.;Guengerich, F. Peter
在研究O-6-烷基鸟嘌呤-DNA烷基转移酶（AGT，MGMT）增强1，2-二溴乙烷诱导的DNA碱基对突变的过程中，我们发现AGT可以与DNA中的一个脱碱基位点发生共价交联。AGT的结合不同于蛋白质HMCES报告的机制;相反，它似乎涉及形成稳定的硫代糖苷。与AGT一样，木瓜蛋白酶和三肽谷胱甘肽也具有低pK（a）半胱氨酸，在木瓜蛋白酶中也观察到了容易的交联。
In the course of studies on the enhancement of 1,2-dibromoethane-induced DNA base pair mutations by O-6-alkylguanine-DNA alkyltransferase (AGT, MGMT), we discovered the facile reaction of AGT with an abasic site in DNA, leading to covalent cross-linking. The binding of AGT differs from the mechanism reported for the protein HMCES; instead it appears to involve formation of a stable thioglycoside. Facile cross-linking was also observed with the protease papain, which like AGT has a low pK(a) cysteine, and the tripeptide glutathione.