Oxidation by 2-oxoglutarate oxygenases: non-haem iron systems in catalysis and signalling
Oxidation by 2-oxoglutarate oxygenases: non-haem iron systems in catalysis and signalling
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DOI：
10.1098/rsta.2004.1540
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发表时间：
2005-04-15
期刊：
影响因子：
5
通讯作者：
Schofield, CJ
中科院分区：
文献类型：
--
作者：
Hewitson, KS;Granatino, N;Schofield, CJ
2-酮戊二酸 (2OG) 和二价铁依赖性加氧酶是酶的超家族，可催化多种反应，包括羟基化、去饱和和氧化闭环。最近，人们发现它们可以作为人类和其他动物缺氧反应的传感器。底物氧化与 2OC 转化为琥珀酸盐和二氧化碳有关。动力学、光谱和结构研究与共识机制一致，其中（共）底物的有序结合能够控制反应中间体。底物与活性位点的结合触发酶将分子氧与金属连接。 2OG 的氧化脱羧随后产生被认为介导底物氧化的ferryl物种。结构研究揭示了一个保守的双链 β-螺旋核心，负责通过 2His-1 羧酸基序和 2OG 侧链结合铁。该核心的刚性与参与结合底物的周围区域的构象灵活性形成对比。在这里，我们从使 2OG 加氧酶适合其功能的通用结构和机械特征方面讨论 2OG 加氧酶的作用。
The 2-oxoglutarate (2OG) and ferrous iron dependent oxygenases are a superfamily of enzymes that catalyse a wide range of reactions including hydroxylations, desaturations and oxidative ring closures. Recently, it has been discovered that they act as sensors ill the hypoxic response in humans and other animals. Substrate oxidation is coupled to conversion of 2OC to succinate and carbon dioxide. Kinetic, spectroscopic and structural studies are consistent with a consensus mechanism in which ordered binding of (co)substrates enables control of reactive intermediates. Binding of the substrate to the active site triggers the enzyme for ligation of dioxygen to the metal. Oxidative decarboxylation of 2OG then generates the ferryl species thought to mediate substrate oxidation. Structural studies reveal a conserved double-stranded beta-helix core responsible for binding the iron, via a 2His-1carboxylate motif and the 2OG side chain. The rigidity of this core contrasts with the conformational flexibility of surrounding regions that are involved in binding the substrate. Here we discuss the roles of 2OG oxygenases in terms of the generic structural and mechanistic features that render the 2OG oxygenases suited for their functions.