Depurination of N7-Methylguanine by DNA Glycosylase AlkD Is Dependent on the DNA Backbone
Depurination of N7-Methylguanine by DNA Glycosylase AlkD Is Dependent on the DNA Backbone
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DOI：
10.1021/bi401195r
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发表时间：
2013-10-22
期刊：
影响因子：
2.9
通讯作者：
Eichman, Brandt F.
中科院分区：
文献类型：
--
作者：
Rubinson, Emily H.;Christov, Plamen P.;Eichman, Brandt F.
DNA糖基化酶AlkD通过一种独特但未知的机制切除N7-甲基鸟嘌呤（7 mG），其中受损的核苷酸远离蛋白质定位，磷酸骨架扭曲。在这里，我们通过甲基膦酸酯取代，近端病变的磷酸盐对酶的7 mG脱嘌呤的速率增强有显着的影响。因此，代替蛋白质侧链参与N-糖苷键裂解的常规机制，AlkD将DNA重塑成仅由DNA官能团组成的活性位点，所述DNA官能团提供催化脱嘌呤的必要化学。
DNA glycosylase AlkD excises N7-methylguanine (7mG) by a unique but unknown mechanism, in which the damaged nucleotide is positioned away from the protein and the phosphate backbone is distorted. Here, we show by methylphosphonate substitution that a phosphate proximal to the lesion has a significant effect on the rate enhancement of 7mG depurination by the enzyme. Thus, instead of a conventional mechanism whereby protein side chains participate in N-glycosidic bond cleavage, AlkD remodels the DNA into an active site composed exclusively of DNA functional groups that provide the necessary chemistry to catalyze depurination.