5IA9
The structure of microsomal glutathione transferase 1 in complex with Meisenheimer complex
Summary for 5IA9
| Entry DOI | 10.2210/pdb5ia9/pdb |
| EMDB information | 8084 |
| Descriptor | Microsomal glutathione S-transferase 1, 1-(S-GLUTATHIONYL)-2,4,6-TRINITROCYCLOHEXA-2,5-DIENE, 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (4 entities in total) |
| Functional Keywords | membrane, enzyme, meisenheimer complex, transferase |
| Biological source | Rattus norvegicus (Norway Rat) |
| Cellular location | Microsome: P08011 |
| Total number of polymer chains | 1 |
| Total formula weight | 20106.05 |
| Authors | Kuang, Q.,Purhonen, P.,Jegerschold, C.,Morgenstern, R.,Hebert, H. (deposition date: 2016-02-21, release date: 2017-07-12, Last modification date: 2025-05-07) |
| Primary citation | Kuang, Q.,Purhonen, P.,Alander, J.,Svensson, R.,Hoogland, V.,Winerdal, J.,Spahiu, L.,Ottosson-Wadlund, A.,Jegerschold, C.,Morgenstern, R.,Hebert, H. Dead-end complex, lipid interactions and catalytic mechanism of microsomal glutathione transferase 1, an electron crystallography and mutagenesis investigation. Sci Rep, 7:7897-7897, 2017 Cited by PubMed Abstract: 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. PubMed: 28801553DOI: 10.1038/s41598-017-07912-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON CRYSTALLOGRAPHY (3.5 Å) |
Structure validation
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