Heme oxygenation and the widening paradigm of heme degradation.
Heme oxygenation and the widening paradigm of heme degradation.
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血红素氧合和血红素降解范式的扩大。
DOI：
10.1016/j.abb.2013.10.013
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发表时间：
2014-02-15
影响因子：
3.9
通讯作者：
Heinzl G
中科院分区：
文献类型：
--
作者：
Wilks A;Heinzl G
通过血红素加氧酶 (HO) 作用进行的血红素降解是不寻常的，因为它利用血红素作为其自身降解的底物和辅助因子。 H2O 催化血红素依赖氧的降解为胆绿素，并释放 CO 和“游离”铁。从人类到细菌的 H2O 酶的表征揭示了相似的整体结构折叠，这有助于形成独特的反应流形。血红素加氧酶与细胞色素 P450 和过氧化物酶具有相似的 O2 对氢过氧化铁的血红素依赖性激活作用。然而，虽然 P450 促进氢过氧化铁 O-O 键与氧化铁基物种的裂解，但 H2O 稳定氢过氧化铁，促进血红素边缘的羟基化。 H2O 中的替代反应途径是通过血红素结合位点内的构象灵活性和广泛的氢键网络实现的，从而引发血红素羟基化。直到最近，人们还认为所有血红素降解酶都会将血红素转化为胆绿素和铁，并释放一氧化碳 (CO)。然而，最近金黄色葡萄球菌、炭疽杆菌和结核分枝杆菌的细菌IsdG样血红素降解蛋白的发现扩大了血红素氧化的反应流形。 IsdG 样反应中血红素降解产物的表征表明了一种不同于经典 HO 的机制。在下面的综述中，我们将讨论经典 HO 的结构功能，因为它与 IsdG 样蛋白的新兴替代反应流形相关。
Heme degradation through the action of heme oxygenase (HO) is unusual in that it utilizes heme as both a substrate and cofactor for its own degradation. HO catalyzes the oxygen-dependent degradation of heme to biliverdin with the release of CO and “free” iron. The characterization of HO enzymes from humans to bacteria reveals a similar overall structural fold that contributes to the unique reaction manifold. The heme oxygenases share a similar heme-dependent activation of O2 to the ferric hydroperoxide as that of the cytochrome P450s and peroxidases. However, whereas the P450s promote cleavage of the ferric hydroperoxide O—O bond to the oxoferryl species the HOs stabilize the ferric hydroperoxide promoting hydroxylation at the heme edge. The alternate reaction pathway in HO is achieved through the conformational flexibility and extensive hydrogen bond network within the heme binding site priming the heme for hydroxylation. Until recently it was believed that all heme degrading enzymes converted heme to biliverdin and iron, with the release of carbon monoxide (CO). However, the recent discovery of the bacterial IsdG-like heme degrading proteins of Staphylococcus aureus, Bacillus anthracis and Mycobacterium tuberculosis has expanded the reaction manifold of heme oxidation. Characterization of the heme degradation products in the IsdG-like reaction suggests a mechanism distinct from the classical HOs. In the following review we will discuss the structure–function of the canonical HOs as it relates to the emerging alternate reaction manifold of the IsdG-like proteins.
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影响因子：
3.9
作者：
DOCHERTY, JC;FIRNEISZ, GD;SCHACTER, BA
通讯作者：
SCHACTER, BA
影响因子：
15
作者：
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通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
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影响因子：
4.1
作者：
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通讯作者：
BROWN, SB
影响因子：
15
作者：
Fujii, H;Zhang, XH;Yoshida, T
通讯作者：
Yoshida, T