1U87

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.50 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.199 

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Ligand Structure Quality Assessment 


This is version 1.6 of the entry. See complete history


Literature

Crystallographic and Thermodynamic Analysis of the Binding of S-Octylglutathione to the Tyr 7 to Phe Mutant of Glutathione S-Transferase from Schistosoma japonicum(,)

Andujar-Sanchez, M.Smith, A.W.Clemente-Jimenez, J.M.Rodriguez-Vico, F.Las Heras-Vazquez, F.J.Jara-Perez, V.Camara-Artigas, A.

(2005) Biochemistry 44: 1174-1183

  • DOI: https://doi.org/10.1021/bi0483110
  • Primary Citation of Related Structures:  
    1U87, 1U88

  • 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.


  • Organizational Affiliation

    Departamento Química Física, Bioquímica y Química Inorgánica, Universidad de Almería, España.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glutathione S-Transferase 26 kDa218Schistosoma japonicumMutation(s): 1 
EC: 2.5.1.18
UniProt
Find proteins for P08515 (Schistosoma japonicum)
Explore P08515 
Go to UniProtKB:  P08515
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08515
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GSH
Query on GSH

Download Ideal Coordinates CCD File 
B [auth A]GLUTATHIONE
C10 H17 N3 O6 S
RWSXRVCMGQZWBV-WDSKDSINSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.50 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.199 
  • R-Value Observed: 0.199 
  • Space Group: P 63 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 123.05α = 90
b = 123.05β = 90
c = 72.51γ = 120
Software Package:
Software NamePurpose
CNSrefinement
MOSFLMdata reduction
CCP4data scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-02-22
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2012-03-21
    Changes: Non-polymer description
  • Version 1.4: 2017-10-11
    Changes: Data collection
  • Version 1.5: 2021-11-10
    Changes: Database references, Derived calculations
  • Version 1.6: 2023-10-25
    Changes: Data collection, Refinement description