Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, United States.
Chem Res Toxicol. 2022 Oct 17;35(10):1805-1808. doi: 10.1021/acs.chemrestox.2c00068. Epub 2022 Apr 28.
In the course of studies on the enhancement of 1,2-dibromoethane-induced DNA base pair mutations by -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 p cysteine, and the tripeptide glutathione.
在研究 -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 与 DNA 中的无碱基位点很容易发生反应，导致共价交联。AGT 的结合与报道的蛋白质 HMCES 的机制不同；相反，它似乎涉及形成稳定的硫糖苷。蛋白酶木瓜蛋白酶也很容易发生交联，与 AGT 一样，它的半胱氨酸 p 很低，三肽谷胱甘肽也是如此。
