Zharkov Dmitry O, Shoham Gil, Grollman Arthur P
Novosibirsk Institute of Bioorganic Chemistry, Siberian Division of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
DNA Repair (Amst). 2003 Aug 12;2(8):839-62. doi: 10.1016/s1568-7864(03)00084-3.
Until recently, the Fpg family was the only major group of DNA glycosylases for which no structural data existed. Prototypical members of this family, found in eukaryotes as well as prokaryotes, have now been crystallized as free proteins and as complexes with DNA. In this review, we analyze the available structural information for formamidopyrimidine-DNA glycosylase (Fpg) and endonuclease VIII (Nei). Special emphasis is placed on mechanisms by which these enzymes recognize and selectively excise cognate lesions from oxidatively damaged DNA. The problem of lesion recognition is considered in two parts: how the enzyme efficiently locates a single lesion embedded in a vast excess of DNA; and how the lesion is accommodated in a pocket near the active site of the enzyme. Although all crystal structures reported to date for the Fpg family lack the damaged base, functionally important residues that participate in DNA binding and enzyme catalysis have been clearly identified and other residues, responsible for substrate specificity, have been inferred.
直到最近，Fpg家族还是唯一没有结构数据的主要DNA糖基化酶组。该家族的典型成员存在于真核生物和原核生物中，目前已被结晶为游离蛋白以及与DNA的复合物。在本综述中，我们分析了甲酰胺嘧啶-DNA糖基化酶（Fpg）和核酸内切酶VIII（Nei）的现有结构信息。特别强调了这些酶从氧化损伤的DNA中识别并选择性切除同源损伤的机制。损伤识别问题分为两部分：酶如何有效地定位嵌入大量DNA中的单个损伤；以及损伤如何容纳在酶活性位点附近的口袋中。尽管迄今为止报道的Fpg家族所有晶体结构都缺少受损碱基，但已明确鉴定出参与DNA结合和酶催化的功能重要残基，并推断出负责底物特异性的其他残基。
