Product-assisted catalysis in base-excision DNA repair
Product-assisted catalysis in base-excision DNA repair
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DOI：
10.1038/nsb902
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发表时间：
2003-03-01
期刊：
影响因子：
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通讯作者：
Verdine, GL
中科院分区：
文献类型：
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作者：
Fromme, JC;Bruner, SD;Verdine, GL
大多数对DNA中碱基的自发损伤是通过碱基切除DNA修复途径的作用来纠正的。碱基切除修复是由DNA糖基酶启动的，DNA糖基酶是一种病变特异性酶，它拦截DNA中的异常碱基并催化它们的切除。这些蛋白质如何利用一个活性部位完成催化不少于五个连续反应步骤的壮举一直是未知的。为了帮助回答这个问题，我们报道了人8-氧鸟嘌呤DNA糖基酶修复DNA过程中捕获的催化中间体的结构。这种结构和支持的生化结果表明，该酶隔离切除的损伤碱基，并利用它作为辅助因子参与催化。据我们所知，这个例子是第一个记录在案的酶催化反应中产物辅助催化的案例。
Most spontaneous damage to bases in DNA is corrected through the action of the base-excision DNA repair pathway. Base excision repair is initiated by DNA glycosylases, lesion-specific enzymes that intercept aberrant bases in DNA and catalyze their excision. How such proteins accomplish the feat of catalyzing no fewer than five sequential reaction steps using a single active site has been unknown. To help answer this, we report the structure of a trapped catalytic intermediate in DNA repair by human 8-oxoguanine DNA glycosylase. This structure and supporting biochemical results reveal that the enzyme sequesters the excised lesion base and exploits it as a cofactor to participate in catalysis. To our knowledge, the present example represents the first documented case of product-assisted catalysis in an enzyme-catalyzed reaction.