5ia9

The structure of microsomal glutathione transferase 1 in complex with Meisenheimer complex

spinqualitylabelsall models 5ia9, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ia9 is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron crystallography, Resolution 3.5Å Ligands: GTD, PC1, PLM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MGST1_RAT Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Publication Abstract from PubMed Microsomal glutathione transferase 1 (MGST1) is a detoxification enzyme belonging to the Membrane Associated Proteins in Eicosanoid and Glutathione Metabolism (MAPEG) superfamily. Here we have used electron crystallography of two-dimensional crystals in order to determine an atomic model of rat MGST1 in a lipid environment. The model comprises 123 of the 155 amino acid residues, two structured phospholipid molecules, two aliphatic chains and one glutathione (GSH) molecule. The functional unit is a homotrimer centered on the crystallographic three-fold axes of the unit cell. The GSH substrate binds in an extended conformation at the interface between two subunits of the trimer supported by new in vitro mutagenesis data. Mutation of Arginine 130 to alanine resulted in complete loss of activity consistent with a role for Arginine 130 in stabilizing the strongly nucleophilic GSH thiolate required for catalysis. Based on the new model and an electron diffraction data set from crystals soaked with trinitrobenzene, that forms a dead-end Meisenheimer complex with GSH, a difference map was calculated. The map reveals side chain movements opening a cavity that defines the second substrate site. Dead-end complex, lipid interactions and catalytic mechanism of microsomal glutathione transferase 1, an electron crystallography and mutagenesis investigation.,Kuang Q, Purhonen P, Alander J, Svensson R, Hoogland V, Winerdal J, Spahiu L, Ottosson-Wadlund A, Jegerschold C, Morgenstern R, Hebert H Sci Rep. 2017 Aug 11;7(1):7897. doi: 10.1038/s41598-017-07912-3. PMID:28801553 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glutathione S-transferase 3D structures

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