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Crystal Structures of Two Archaeal 8-Oxoguanine DNA Glycosylases Provide Structural Insight into Guanine/8-Oxoguanine Distinction

机译:两种古细菌8-氧鸟嘌呤DNA糖基化酶的晶体结构为鸟嘌呤/ 8-氧鸟嘌呤的区分提供结构见解。

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摘要

Among the four DNA bases, guanine is particularly vulnerable to oxidative damage and the most common oxidative product, 7,8-dihydro-8-oxoguanine (8-oxoG), is the most prevalent lesion observed in DNA molecules. Fortunately, 8-oxoG is recognized and excised by the 8-oxoguanine DNA glycosylase (Ogg) of the base excision repair pathway. 9 enzymes are divided into three separate families, namely, Ogg1, Ogg2, and archaeal GO glycosylase (AGOG). To date, structures of members of both Ogg1 and AGOG families are known but no structural information is available for members of Ogg2. Here we describe the first crystal structures of two archaeal Ogg2: Methanocaldococcus janischii Ogg and Suffolobus soltataricus Ogg. A structural comparison with OGG1 and AGOG suggested that the C-terminal lysine of Ogg2 may play a key role in discriminating between guanine and 8-oxoG. This prediction was substantiated by measuring the glycosylase/lyase activity of a C-terminal deletion mutant of MjaOgg.
机译:在这四个DNA碱基中,鸟嘌呤特别容易受到氧化损伤,最常见的氧化产物7,8-二氢-8-氧鸟嘌呤(8-oxoG)是在DNA分子中观察到的最普遍的病变。幸运的是,碱基切除修复途径的8-oxo鸟嘌呤DNA糖基化酶(Ogg)识别并切除了8-oxoG。 9种酶分为三个独立的家族,即Ogg1,Ogg2和古细菌GO糖基化酶(AGOG)。迄今为止,Ogg1和AGOG家族成员的结构都是已知的,但没有Ogg2成员的结构信息。在这里,我们描述了两个古细菌Ogg2的第一个晶体结构:Methanocaldococcus janischii Ogg和Suffolobus soltataricus Ogg。与OGG1和AGOG的结构比较表明,Ogg2的C端赖氨酸可能在区分鸟嘌呤和8-oxoG方面起关键作用。通过测量MjaOgg的C端缺失突变体的糖基化酶/裂解酶活性,证实了这一预测。

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