在威尔逊氏病条件下，铜抑制AlkB家族DNA修复酶。
Copper Inhibits the AlkB Family DNA Repair Enzymes under Wilson's Disease Condition.
作者信息
Bian Ke, Chen Fangyi, Humulock Zachary T, Tang Qi, Li Deyu
机构信息
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island , Kingston, Rhode Island 02881, United States.
出版信息
Chem Res Toxicol. 2017 Oct 16;30(10):1794-1796. doi: 10.1021/acs.chemrestox.7b00230. Epub 2017 Sep 26.
Abstract
Disturbed metabolism of copper ions can cause diseases such as Wilson's disease (WD). In this work, we investigated the inhibitory effect of Cu(II) ion in vitro on the AlkB family DNA repair enzymes, which are members of the Fe(II)/alpha-ketoglutarate-dependent dioxygenase and include human ALKBH2, ALKBH3, and E. coli AlkB proteins. None of the three proteins was significantly inhibited under normal cellular copper concentrations. However, under WD related condition, we observed that the activities of all three enzymes were strongly suppressed (from 95.2 to 100.0%). We also noted the repair efficiency under ds-DNA condition was less susceptible than ss-DNA to the inhibition.
摘要
铜离子代谢紊乱会引发诸如威尔逊氏病（WD）等疾病。在本研究中，我们研究了Cu(II)离子在体外对AlkB家族DNA修复酶的抑制作用，这些酶是Fe(II)/α-酮戊二酸依赖性双加氧酶的成员，包括人类ALKBH2、ALKBH3和大肠杆菌AlkB蛋白。在正常细胞铜浓度下，这三种蛋白质均未受到显著抑制。然而，在与WD相关的条件下，我们观察到所有三种酶的活性均受到强烈抑制（从95.2%到100.0%）。我们还注意到，在双链DNA条件下的修复效率比单链DNA对抑制作用的敏感性更低。
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