Structural basis for detoxification and oxidative stress protection in membranes
Structural basis for detoxification and oxidative stress protection in membranes
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DOI：
10.1016/j.jmb.2006.05.056
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发表时间：
2006-07-28
影响因子：
5.6
通讯作者：
Hebert, Hans
中科院分区：
文献类型：
--
作者：
Holm, Peter J.;Bhakat, Priyaranjan;Hebert, Hans
发烧、疼痛和炎症介质的合成以及针对反应性分子和氧化应激的保护是 MAPEG 超家族（类二十烷酸和谷胱甘肽代谢中的膜相关蛋白）的标志。 MAPEG 成员（大鼠线粒体谷胱甘肽转移酶 1）的结构，分辨率为 3.2 埃，通过电子晶体学与谷胱甘肽形成复合物，定义了活性位点位置和参与酶激活的胞质结构域。发现谷胱甘肽结合位点与典型的可溶性谷胱甘肽转移酶的结合位点不同。同源三聚体的结构支持涉及亚基相互作用的催化机制，并揭示了胞质和膜底物进入位点，为酶的膜定位提供了理论依据。 (c) 2006 Elsevier Ltd. 保留所有权利。
Synthesis of mediators of fever, pain and inflammation as well as protection against reactive molecules and oxidative stress is a hallmark of the MAPEG superfamily (membrane associated proteins in eicosanoid and glutathione metabolism). The structure of a MAPEG member, rat mictosomal glutathione transferase 1, at 3.2 angstrom resolution, solved here in complex with glutathione by electron crystallography, defines the active site location and a cytosolic domain involved in enzyme activation. The glutathione binding site is found to be different from that of the canonical soluble glutathione transferases. The architecture of the homotrimer supports a catalytic mechanism involving subunit interactions and reveals both cytosolic and membraneous substrate entry sites, providing a rationale for the membrane location of the enzyme. (c) 2006 Elsevier Ltd. All rights reserved.