Switching Demethylation Activities between AlkB Family RNA/DNA Demethylases through Exchange of Active-Site Residues
Switching Demethylation Activities between AlkB Family RNA/DNA Demethylases through Exchange of Active-Site Residues
复制标题
通过交换活性位点残基来切换 AlkB 家族 RNA/DNA 去甲基化酶之间的去甲基化活性
DOI：
10.1002/anie.201310050
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发表时间：
2014-04-01
影响因子：
16.6
通讯作者：
Yi, Chengqi
中科院分区：
文献类型：
--
作者：
Zhu, Chenxu;Yi, Chengqi
AlkB 家族去甲基化酶 AlkB、FTO 和 ALKBH5 可识别差异甲基化的 RNA/DNA 底物，从而发挥其独特的生物学作用。在这里，我们确定了有助于其底物特异性的关键活性位点残基。在去甲基化酶之间交换此类活性位点残基会导致部分去甲基化活性的转换。 X 射线结构和酶动力学的综合证据表明活性位点残基在底物识别中的作用。这种不同的活性位点序列可能有助于设计能够区分这些同源 RNA/DNA 去甲基酶的选择性抑制剂。
The AlkB family demethylases AlkB, FTO, and ALKBH5 recognize differentially methylated RNA/DNA substrates, which results in their distinct biological roles. Here we identify key active-site residues that contribute to their substrate specificity. Swapping such active-site residues between the demethylases leads to partially switched demethylation activities. Combined evidence from X-ray structures and enzyme kinetics suggests a role of the active-site residues in substrate recognition. Such a divergent active-site sequence may aid the design of selective inhibitors that can discriminate these homologue RNA/DNA demethylases.