The three-dimensional map of microsomal glutathione transferase 1 at 6 angstrom resolution

Microsomal glutathione transferase 1 (MGST1) is representative of a superfa mily of membrane proteins where different members display distinct or overl apping physiological functions, including detoxication of reactive electrop hiles (glutathione transferase), reduction of lipid hydroperoxides (glutath ione peroxidase), and production of leukotrienes and prostaglandin E. It fo llows that members of this superfamily constitute important drug targets re garding asthma, inflammation and the febrile response. Here we propose that this superfamily consists of a new class of membrane proteins built on a c ommon left-handed four-helix bundle motif within the membrane, as determine d by electron crystallography of MGST1 at 6 Angstrom resolution. Based on t he 3D map and biochemical data we discuss a model for the membrane topology . The 3D structure differs significantly from that of soluble glutathione t ransferases, which display overlapping substrate specificity with MGST1.