分辨率为6埃的微粒体谷胱甘肽转移酶1的三维图谱。
The three-dimensional map of microsomal glutathione transferase 1 at 6 A resolution.
作者信息
Schmidt-Krey I, Mitsuoka K, Hirai T, Murata K, Cheng Y, Fujiyoshi Y, Morgenstern R, Hebert H
机构信息
Karolinska Institutet, Center for Structural Biochemistry, Department of Biosciences, Novum, S-141 57 Huddinge, Germany.
出版信息
EMBO J. 2000 Dec 1;19(23):6311-6. doi: 10.1093/emboj/19.23.6311.
Microsomal glutathione transferase 1 (MGST1) is representative of a superfamily of membrane proteins where different members display distinct or overlapping physiological functions, including detoxication of reactive electrophiles (glutathione transferase), reduction of lipid hydroperoxides (glutathione peroxidase), and production of leukotrienes and prostaglandin E. It follows that members of this superfamily constitute important drug targets regarding asthma, inflammation and the febrile response. Here we propose that this superfamily consists of a new class of membrane proteins built on a common left-handed four-helix bundle motif within the membrane, as determined by electron crystallography of MGST1 at 6 A resolution. Based on the 3D map and biochemical data we discuss a model for the membrane topology. The 3D structure differs significantly from that of soluble glutathione transferases, which display overlapping substrate specificity with MGST1.
微粒体谷胱甘肽转移酶1（MGST1）是膜蛋白超家族的代表，该超家族的不同成员具有不同或重叠的生理功能，包括对活性亲电试剂的解毒作用（谷胱甘肽转移酶）、脂质氢过氧化物的还原作用（谷胱甘肽过氧化物酶）以及白三烯和前列腺素E的生成。因此，这个超家族的成员构成了与哮喘、炎症和发热反应相关的重要药物靶点。在此我们提出，这个超家族由一类新的膜蛋白组成，这些膜蛋白基于膜内常见的左手四螺旋束基序构建，这是通过MGST1在6埃分辨率下的电子晶体学确定的。基于三维图谱和生化数据，我们讨论了膜拓扑结构模型。其三维结构与可溶性谷胱甘肽转移酶有显著差异，可溶性谷胱甘肽转移酶与MGST1具有重叠的底物特异性。
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