5I9K

The structure of microsomal glutathione transferase 1

5I9K の概要

• エントリーDOI: 10.2210/pdb5i9k/pdb
• EMDBエントリー: 8076
• 分子名称: Microsomal glutathione S-transferase 1, GLUTATHIONE, 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (4 entities in total)
• 機能のキーワード: membrane, enzyme, four-helical bundle, trimer, transferase
• 由来する生物種: Rattus norvegicus (Norway Rat)
• 細胞内の位置: Microsome: P08011
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19892.95

構造登録者

Kuang, Q.,Purhonen, P.,Jegerschold, C.,Morgenstern, R.,Hebert, H. (登録日: 2016-02-20, 公開日: 2017-07-12, 最終更新日: 2017-08-23)

主引用文献

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

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: 28801553
DOI: 10.1038/s41598-017-07912-3

実験手法

ELECTRON CRYSTALLOGRAPHY (3.5 Å)