Structures of aminophenol dioxygenase in complex with intermediate, product and inhibitor.
Structures of aminophenol dioxygenase in complex with intermediate, product and inhibitor.
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DOI：
10.1107/s0907444912042072
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发表时间：
2013
期刊：
影响因子：
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通讯作者：
De-Feng Li;Jia Yue Zhang;Yanjie Hou;Lei Liu;Yonglin Hu;Shuang Liu;Da Cheng Wang;Wei Liu
中科院分区：
文献类型：
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作者：
De-Feng Li;Jia Yue Zhang;Yanjie Hou;Lei Liu;Yonglin Hu;Shuang Liu;Da Cheng Wang;Wei Liu
近年来，含有2-His-1-carboxylic facial triad的非血红素Fe（II）酶对分子氧的活化作用得到了广泛的研究。在这里，2-氨基苯酚1，6-双加氧酶，一种酶，代表一个小组的extradiol双加氧酶和催化2-氨基苯酚的开环，在复杂的内酯中间体（4 Z，6 Z）-3-亚氨基氧杂环庚烯-2（3 H）-酮和产品2-aminomuconic 6-semialdehyde和复杂的自杀抑制剂4-硝基儿茶酚的晶体结构的报告。在这些结构中观察到的Fe-配体结合方案揭示了一些共同的几何特征，这些特征是由extradiol双加氧酶的已发表结构所共有的，这表明催化非儿茶酚化合物氧化的酶很可能利用类似的双氧活化和芳环裂变策略作为典型机制。然而，Fe-连接排列与除原儿茶酸4，5-双加氧酶之外的所有其他2-His-1-羧酸酶的排列是惊人的对映体。这种结构差异导致在O（2）结合之前产生不常见的O（-）-Fe（2+）-O（-）物种，这可能形成APD区分其特异性底物和抑制剂的结构基础，它们具有相似的分子结构。
Dioxygen activation by nonhaem Fe(II) enzymes containing the 2-His-1-carboxylate facial triad has been extensively studied in recent years. Here, crystal structures of 2-aminophenol 1,6-dioxygenase, an enzyme that represents a minor group of extradiol dioxygenases and that catalyses the ring opening of 2-aminophenol, in complex with the lactone intermediate (4Z,6Z)-3-iminooxepin-2(3H)-one and the product 2-aminomuconic 6-semialdehyde and in complex with the suicide inhibitor 4-nitrocatechol are reported. The Fe-ligand binding schemes observed in these structures revealed some common geometrical characteristics that are shared by the published structures of extradiol dioxygenases, suggesting that enzymes that catalyse the oxidation of noncatecholic compounds are very likely to utilize a similar strategy for dioxygen activation and the fission of aromatic rings as the canonical mechanism. The Fe-ligation arrangement, however, is strikingly enantiomeric to that of all other 2-His-1-carboxylate enzymes apart from protocatechuate 4,5-dioxygenase. This structural variance leads to the generation of an uncommon O(-)-Fe(2+)-O(-) species prior to O(2) binding, which probably forms the structural basis on which APD distinguishes its specific substrate and inhibitor, which share an analogous molecular structure.