Structural basis for detoxification and oxidative stress protection in membranes |
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Authors: | Holm Peter J Bhakat Priyaranjan Jegerschöld Caroline Gyobu Nobuhiko Mitsuoka Kaoru Fujiyoshi Yoshinori Morgenstern Ralf Hebert Hans |
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Institution: | Department of Biosciences and Nutrition, Karolinska Institutet and School of Technology and Health, Royal Institute of Technology, SE-14157 Huddinge, Sweden. |
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Abstract: | 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 microsomal glutathione transferase 1, at 3.2 A 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. |
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Keywords: | GST glutathione transferase MAPEG membrane associated proteins in eicosanoid and glutathione metabolism MGST1 microsomal glutathione transferase 1 GSH tri-peptide glutathione |
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