1U88 : Crystal Structure Of The 26 Kda Glutathione S-Transferase Y7F mutant From Schistosoma Japonicum Complexed With S-Octyl Glutathione

  • A. W. Smith (Contributor)
  • A. Cámara-Artigas (Contributor)

Dataset

Description

Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:3.5
Classification:TRANSFERASE
Release Date:2005-02-22
Deposition Date:2004-08-05
Revision Date:2008-04-30#2011-07-13
Molecular Weight:51456.98
Macromolecule Type:Protein
Residue Count:436
Atom Site Count:3486
DOI:10.2210/pdb1u88/pdb

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.
Date made availableFeb 22 2005
PublisherRCSB-PDB

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