myo-Inositol oxygenase: a radical new pathway for O2 and C-H activation at a nonheme diiron cluster
myo-Inositol oxygenase: a radical new pathway for O2 and C-H activation at a nonheme diiron cluster
复制标题
DOI：
10.1039/b811885j
复制
发表时间：
2009-01-01
影响因子：
4
通讯作者：
Krebs, Carsten
中科院分区：
文献类型：
--
作者：
Bollinger, J. Martin, Jr.;Diao, Yinghui;Krebs, Carsten
肌醇加氧酶（MIOX）催化肌醇（环己-1，2，3，5/4，6-六醇或MI）转化为D-葡萄糖醛酸（DG），启动人类中唯一已知的细胞信号肌醇（多）磷酸和磷酸肌醇碳骨架催化剂的途径。最近的动力学，光谱学和晶体学研究表明，酶激活其底物，MI和O-2，在一个羧基桥接nonheme二铁（II/III）簇，使其成为第一个许多已知的nonheme二铁加氧酶采用混合价形式的辅因子。证据表明：（1）Fe（III）位点通过其C1和C6羟基与MI配位;（2）Fe（II）位点可逆地与O-2配位以产生超氧代二铁（III/III）中间体;和（3）超氧化物配体的侧氧原子从C1夺取氢以引发独特的C-C键断裂、四电子氧化反应。本文综述了导致认识到新的辅因子要求和催化机制的MIOX的研究，并预测如何在我们的理解剩余的差距可能会填补额外的实验。
The enzyme myo-inositol oxygenase (MIOX) catalyzes conversion of myo-inositol (cyclohexan-1,2,3,5/4,6-hexa-ol or MI) to D-glucuronate (DG), initiating the only known pathway in humans for catabolism of the carbon skeleton of cell-signaling inositol (poly) phosphates and phosphoinositides. Recent kinetic, spectroscopic and crystallographic studies have shown that the enzyme activates its substrates, MI and O-2, at a carboxylate-bridged nonheme diiron(II/III) cluster, making it the first of many known nonheme diiron oxygenases to employ the mixed-valent form of its cofactor. Evidence suggests that: (1) the Fe(III) site coordinates MI via its C1 and C6 hydroxyl groups; (2) the Fe(II) site reversibly coordinates O-2 to produce a superoxo-diiron(III/III) intermediate; and (3) the pendant oxygen atom of the superoxide ligand abstracts hydrogen from C1 to initiate the unique C-C-bond-cleaving, four-electron oxidation reaction. This review recounts the studies leading to the recognition of the novel cofactor requirement and catalytic mechanism of MIOX and forecasts how remaining gaps in our understanding might be filled by additional experiments.