Xiaofeng Zhu, Xuan Yan, Lester G Carter, Huanting Liu, Shirley Graham, Peter J Coote, James Naismith
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引用次数: 0
摘要
清除化学损伤的 DNA 碱基（如 3-甲基腺嘌呤 (3-MeA)）是所有生物体内的一个基本过程，由 3-MeA DNA 糖基化酶 I 催化。一个关键问题是该酶如何选择性地识别烷基化的 3-MeA 而不是含量更高的腺嘌呤。据报道，来自金黄色葡萄球菌的原生和 Y16F 突变的 3-MeA DNA 糖基化酶 I 与 3-MeA 复合物的晶体结构分辨率分别为 1.8 和 2.2 Å。等温滴定量热法显示，3-MeA 的质子化会降低其结合亲和力，这证实了之前的荧光研究，即电荷识别对于选择 3-MeA 而不是腺嘌呤并不重要。据推测，3-MeA DNA 糖基化酶 I 的 Glu38 和 Tyr16 与 3-MeA 独有的特定同系物的氢键模式有助于识别和选择。
A model for 3-methyladenine recognition by 3-methyladenine DNA glycosylase I (TAG) from Staphylococcus aureus.
The removal of chemically damaged DNA bases such as 3-methyladenine (3-MeA) is an essential process in all living organisms and is catalyzed by the enzyme 3-MeA DNA glycosylase I. A key question is how the enzyme selectively recognizes the alkylated 3-MeA over the much more abundant adenine. The crystal structures of native and Y16F-mutant 3-MeA DNA glycosylase I from Staphylococcus aureus in complex with 3-MeA are reported to 1.8 and 2.2 Å resolution, respectively. Isothermal titration calorimetry shows that protonation of 3-MeA decreases its binding affinity, confirming previous fluorescence studies that show that charge-charge recognition is not critical for the selection of 3-MeA over adenine. It is hypothesized that the hydrogen-bonding pattern of Glu38 and Tyr16 of 3-MeA DNA glycosylase I with a particular tautomer unique to 3-MeA contributes to recognition and selection.
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