Crystal structure of the non-haem iron halogenase SyrB2 in syringomycin biosynthesis
Crystal structure of the non-haem iron halogenase SyrB2 in syringomycin biosynthesis
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DOI：
10.1038/nature04544
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发表时间：
2006-03-16
期刊：
影响因子：
64.8
通讯作者：
Drennan, CL
中科院分区：
文献类型：
--
作者：
Blasiak, LC;Vaillancourt, FH;Drennan, CL
非血红素Fe（II）/α-酮戊二酸（α KG）依赖性酶利用α KG的还原能力来催化氧化反应，通常是未活性碳的羟基化，并且参与诸如天然产物生物合成、哺乳动物缺氧反应和DNA修复的过程（1，2）。这些酶将α KG的脱羧作用与作为夺氢物质的高能铁酰基-氧代中间体的形成偶联（2 - 4）。所有以前的结构特征单核铁酶含有2-组氨酸，1-羧酸基序，协调铁（1，2）。两个组氨酸和一个羧酸盐，被称为“面三元组”，形成八面体铁配位几何结构的一个三角形侧面。单核铁酶的一个亚类已被证明催化卤化反应，而不是更典型的羟基化反应（5，6）。SyrB2是该亚类的一个成员，是一种非血红素Fe（II）/α KG依赖性卤化酶，其在瑞幸霉素E生物合成中催化苏氨酸的氯化（5）。在这里，我们报告的结构SyrB2与氯离子和α KG协调的铁离子在1.6埃的分辨率。这个结构揭示了一个以前未知的铁的配位，其中的羧酸配体的面三元组被氯离子取代。
Non- haem Fe( II)/ alpha-ketoglutarate ( alpha KG)- dependent enzymes harness the reducing power of alpha KG to catalyse oxidative reactions, usually the hydroxylation of unactivated carbons, and are involved in processes such as natural product biosynthesis, the mammalian hypoxic response, and DNA repair(1,2). These enzymes couple the decarboxylation of alpha KG with the formation of a high- energy ferryl- oxo intermediate that acts as a hydrogen- abstracting species(2-4). All previously structurally characterized mononuclear iron enzymes contain a 2- His, 1- carboxylate motif that coordinates the iron(1,2). The two histidines and one carboxylate, known as the ' facial triad', form one triangular side of an octahedral iron coordination geometry. A subclass of mononuclear iron enzymes has been shown to catalyse halogenation reactions, rather than the more typical hydroxylation reaction(5,6). SyrB2, a member of this subclass, is a non- haem Fe( II)/ alpha KG-dependent halogenase that catalyses the chlorination of threonine in syringomycin E biosynthesis(5). Here we report the structure of SyrB2 with both a chloride ion and alpha KG coordinated to the iron ion at 1.6 angstrom resolution. This structure reveals a previously unknown coordination of iron, in which the carboxylate ligand of the facial triad is replaced by a chloride ion.