1U88

Crystal Structure Of The 26 Kda Glutathione S-Transferase Y7F mutant From Schistosoma Japonicum Complexed With S-Octyl Glutathione

1U88 の概要

• エントリーDOI: 10.2210/pdb1u88/pdb
• 関連するPDBエントリー: 1gne 1gta 1m9a 1U87
• 分子名称: Glutathione S-transferase 26 kDa, L-GAMMA-GLUTAMYL-S-OCTYL-D-CYSTEINYLGLYCINE (2 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Schistosoma japonicum
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51456.98

構造登録者

Smith, A.W.,Camara-Artigas, A. (登録日: 2004-08-05, 公開日: 2005-02-22, 最終更新日: 2024-04-03)

主引用文献

Andujar-Sanchez, M.,Smith, A.W.,Clemente-Jimenez, J.M.,Rodriguez-Vico, F.,Las Heras-Vazquez, F.J.,Jara-Perez, V.,Camara-Artigas, A.
Crystallographic and Thermodynamic Analysis of the Binding of S-Octylglutathione to the Tyr 7 to Phe Mutant of Glutathione S-Transferase from Schistosoma japonicum(,)
Biochemistry, 44:1174-1183, 2005

PubMed Abstract: Glutathione S-transferases are a family of multifunctional enzymes involved in the metabolism of drugs and xenobiotics. Two tyrosine residues, Tyr 7 and Tyr 111, in the active site of the enzyme play an important role in the binding and catalysis of substrate ligands. The crystal structures of Schistosoma japonicum glutathione S-transferase tyrosine 7 to phenylalanine mutant [SjGST(Y7F)] in complex with the substrate glutathione (GSH) and the competitive inhibitor S-octylglutathione (S-octyl-GSH) have been obtained. These new structural data combined with fluorescence spectroscopy and thermodynamic data, obtained by means of isothermal titration calorimetry, allow for detailed characterization of the ligand-binding process. The binding of S-octyl-GSH to SjGST(Y7F) is enthalpically and entropically driven at temperatures below 30 degrees C. The stoichiometry of the binding is one molecule of S-octyl-GSH per mutant dimer, whereas shorter alkyl derivatives bind with a stoichiometry of two molecules per mutant dimer. The SjGST(Y7F).GSH structure showed no major structural differences compared to the wild-type enzyme. In contrast, the structure of SjGST(Y7F).S-octyl-GSH showed asymmetric binding of S-octyl-GSH. This lack of symmetry is reflected in the lower symmetry space group of the SjGST(Y7F).S-octyl-GSH crystals (P6(3)) compared to that of the SjGST(Y7F).GSH crystals (P6(3)22). Moreover, the binding of S-octyl-GSH to the A subunit is accompanied by conformational changes that may be responsible for the lack of binding to the B subunit.

PubMed: 15667211
DOI: 10.1021/bi0483110

実験手法

X-RAY DIFFRACTION (3.5 Å)