4IS0

Structural Insights into Omega-Class Glutathione Transferases: A Snapshot of Enzyme Reduction and Identification of the Non-Catalytic Ligandin Site.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.72 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.152 
  • R-Value Observed: 0.155 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural insights into omega-class glutathione transferases: a snapshot of enzyme reduction and identification of a non-catalytic ligandin site.

Brock, J.Board, P.G.Oakley, A.J.

(2013) PLoS One 8: e60324-e60324

  • DOI: https://doi.org/10.1371/journal.pone.0060324
  • Primary Citation of Related Structures:  
    4IS0

  • PubMed Abstract: 

    Glutathione transferases (GSTs) are dimeric enzymes containing one active-site per monomer. The omega-class GSTs (hGSTO1-1 and hGSTO2-2 in humans) are homodimeric and carry out a range of reactions including the glutathione-dependant reduction of a range of compounds and the reduction of S-(phenacyl)glutathiones to acetophenones. Both types of reaction result in the formation of a mixed-disulfide of the enzyme with glutathione through the catalytic cysteine (C32). Recycling of the enzyme utilizes a second glutathione molecule and results in oxidized glutathione (GSSG) release. The crystal structure of an active-site mutant (C32A) of the hGSTO1-1 isozyme in complex with GSSG provides a snapshot of the enzyme in the process of regeneration. GSSG occupies both the G (GSH-binding) and H (hydrophobic-binding) sites and causes re-arrangement of some H-site residues. In the same structure we demonstrate the existence of a novel "ligandin" binding site deep within in the dimer interface of this enzyme, containing S-(4-nitrophenacyl)glutathione, an isozyme-specific substrate for hGSTO1-1. The ligandin site, conserved in Omega class GSTs from a range of species, is hydrophobic in nature and may represent the binding location for tocopherol esters that are uncompetitive hGSTO1-1 inhibitors.


  • Organizational Affiliation

    Research School of Chemistry, Australian National University, Canberra, Australian Capital Territory, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glutathione S-transferase omega-1241Homo sapiensMutation(s): 1 
Gene Names: GSTO1GSTTLP28
EC: 2.5.1.18 (PDB Primary Data), 1.8.5.1 (PDB Primary Data), 1.20.4.2 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for P78417 (Homo sapiens)
Explore P78417 
Go to UniProtKB:  P78417
PHAROS:  P78417
GTEx:  ENSG00000148834 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP78417
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.72 Å
  • R-Value Free: 0.201 
  • R-Value Work: 0.152 
  • R-Value Observed: 0.155 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.6α = 90
b = 57.6β = 90
c = 140.176γ = 120
Software Package:
Software NamePurpose
Blu-Icedata collection
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-04-24
    Type: Initial release
  • Version 1.1: 2013-07-03
    Changes: Database references
  • Version 1.2: 2017-11-15
    Changes: Advisory, Refinement description
  • Version 1.3: 2023-09-20
    Changes: Advisory, Data collection, Database references, Derived calculations, Refinement description