1U87

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

Summary for 1U87

• Entry DOI: 10.2210/pdb1u87/pdb
• Related: 1U88 1gne 1gta
• Descriptor: Glutathione S-Transferase 26 kDa, GLUTATHIONE (2 entities in total)
• Functional Keywords: transferase
• Biological source: Schistosoma japonicum
• Total number of polymer chains: 1
• Total formula weight: 25826.04

Authors

Smith, A.W.,Camara-Artigas, A. (deposition date: 2004-08-05, release date: 2005-02-22, Last modification date: 2023-10-25)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.5 Å)