The crystal structures of the ferric and ferrous forms of the heme complex of HmuO, a heme oxygenase of Corynebacterium diphtheriae
The crystal structures of the ferric and ferrous forms of the heme complex of HmuO, a heme oxygenase of Corynebacterium diphtheriae
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DOI：
10.1074/jbc.m311631200
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发表时间：
2004-03-19
影响因子：
4.8
通讯作者：
Ikeda-Saito, M
中科院分区：
文献类型：
--
作者：
Hirotsu, S;Chu, GC;Ikeda-Saito, M
铁和亚铁血红素复合物的HmuO，24 kDa血红素加氧酶的白喉棒状杆菌的晶体结构，已被细化到1.4和1.5埃的分辨率，分别。的HmuO结构表明，血红素组是紧密夹在近端和远端螺旋之间。His-20的咪唑基团是近端血红素配体，其紧密地遮蔽卟啉环的β-和δ-中轴。存在长程氢键网络，将铁结合的水配体连接到溶剂水分子。这使得质子能够从溶剂转移到催化位点，在催化位点处发生氧活化。与铁络合物相比，亚铁络合物中的近端和远端螺旋更靠近血红素平面。与扭结的远端螺旋一起，这种运动只留下α-中位碳原子与铁结合的分子氧接触。血红素口袋结构负责通过防止过早的异裂O-O键断裂来稳定铁氢过氧活性中间体。这允许酶在HmuO催化中选择性地在α-内消旋碳上进行重排。
Crystal structures of the ferric and ferrous heme complexes of HmuO, a 24-kDa heme oxygenase of Corynebacterium diphtheriae, have been refined to 1.4 and 1.5 Angstrom resolution, respectively. The HmuO structures show that the heme group is closely sandwiched between the proximal and distal helices. The imidazole group of His-20 is the proximal heme ligand, which closely eclipses the beta- and delta-meso axis of the porphyrin ring. A long range hydrogen bonding network is present, connecting the iron-bound water ligand to the solvent water molecule. This enables proton transfer from the solvent to the catalytic site, where the oxygen activation occurs. In comparison to the ferric complex, the proximal and distal helices move closer to the heme plane in the ferrous complex. Together with the kinked distal helix, this movement leaves only the alpha-meso carbon atom accessible to the iron-bound dioxygen. The heme pocket architecture is responsible for stabilization of the ferric hydroperoxo-active intermediate by preventing premature heterolytic O-O bond cleavage. This allows the enzyme to oxygenate selectively at the alpha-meso carbon in HmuO catalysis.