Structure and Catalytic Mechanism of Heme Oxygenase
Structure and Catalytic Mechanism of Heme Oxygenase
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DOI：
10.1002/chin.200736271
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发表时间：
2007-09
期刊：
影响因子：
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通讯作者：
M. Unno;T. Matsui;M. Ikeda-Saito
中科院分区：
文献类型：
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作者：
M. Unno;T. Matsui;M. Ikeda-Saito
覆盖范围：截至2006年 血红素加氧酶（HO）催化血红素在O2依赖下区域特异性地转化为胆绿素、CO和游离Fe（II）。血红素基团紧紧夹在“近端”和“远端”螺旋之间，其中His的中性咪唑作为轴向配体。在亚铁形式中，两个螺旋都更靠近血红素基团，并且O2以大约110°的锐角Fe-O-O结合，远端螺旋限制O-O键的方向，使末端氧原子靠近α-中间碳。结合O2是稳定的氢键与远端Gly酰胺氮和附近的H2O，后者是一个扩展的远端口袋氢键网络的一部分，由保守的远端Asp连接。氢键网络充当用于转移形成氢过氧铁所需的质子的管道，所述氢过氧铁通过氧形式的单电子还原产生，并且还用于活化氢过氧铁，导致血红素α-中位碳的选择性羟基化。铁过氧化氢活性物种不能形成后，附近的H2O的损失，表明该H2O分子中的中间碳羟基化的关键作用。亚铁绿血红素的形成是由α-meso-羟基亚铁血红素的亚铁卟啉中性自由基与O2和一个电子反应进行的。亚铁绿血红素铁与O2反应形成反应中间体，其还原得到胆绿素。通过远端口袋氢键网络的质子转移促进绿血红素转化为胆绿素。HO血红素催化剂是通过突出的HO蛋白结构实现的，该HO蛋白结构能够将相当惰性的血红素转化为反应性羟基血红素和绿血红素中间体。
Covering: up to 2006 Heme oxygenase (HO) catalyzes O2-dependent regiospecific conversion of heme to biliverdin, CO and free Fe(II). The heme group is tightly sandwiched between the “proximal” and “distal” helices with a neutral imidazole of His as an axial ligand. In the ferrous form, both helices move closer to the heme group, and O2 binds with an acute Fe–O–O angle of ∼110°, the distal helix restricts the O–O bond direction placing the terminal oxygen atom close to the α-meso-carbon. The bound O2 is stabilized by hydrogen bonds with a distal Gly amide nitrogen and the nearby H2O, the latter of which is a part of an extended distal pocket hydrogen bonding network linked by a conserved distal Asp. The hydrogen bonding network functions as a conduit for transferring protons required for the formation of the ferric hydroperoxo, generated by one-electron reduction of the oxy form, and also for the activation of the hydroperoxo, leading to the selective hydroxylation of the heme α-meso-carbon. The ferric hydroperoxo active species could not be formed upon loss of the nearby H2O, indicating a critical role of this H2O molecule in the meso-carbon hydroxylation. Ferrous verdoheme formation proceeds by reaction of the ferrous porphyrin neutral radical of ferric α-meso-hydroxyheme with O2 and one electron. Ferrous verdoheme iron reacts with O2 to form a reaction intermediate, reduction of which affords biliverdin. Proton transfer by the distal pocket hydrogen bonding network facilitates conversion of verdoheme to biliverdin. HO heme catabolism is realized by the salient HO protein structure that enables conversion of heme, which is rather inert, into reactive hydroxyheme and verdoheme intermediates.