3GSS

HUMAN GLUTATHIONE S-TRANSFERASE P1-1 IN COMPLEX WITH ETHACRYNIC ACID-GLUTATHIONE CONJUGATE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

The three-dimensional structure of the human Pi class glutathione transferase P1-1 in complex with the inhibitor ethacrynic acid and its glutathione conjugate.

Oakley, A.J.Rossjohn, J.Lo Bello, M.Caccuri, A.M.Federici, G.Parker, M.W.

(1997) Biochemistry 36: 576-585

  • DOI: https://doi.org/10.1021/bi962316i
  • Primary Citation of Related Structures:  
    2GSS, 3GSS

  • PubMed Abstract: 

    The potent diuretic drug ethacrynic acid has been tested in clinical trials as an adjuvant in chemotherapy. Its target is the detoxifying enzyme glutathione transferase which is often found overexpressed in cancer tissues. We have solved the crystal structures of human pi class glutathione transferase P1-1 in complex with the inhibitor ethacrynic acid and its glutathione conjugate. Ethacrynic acid is found to bind in a nonproductive mode to one of the ligand binding sites of the enzyme (the H site) while the glutathione binding site (G site) is occupied by solvent molecules. There are no structural rearrangements of the G site in the absence of ligand. The structure indicates that bound glutathione is required for ethacrynic acid to dock into the H site in a productive binding mode. The binding of the ethacrynic acid-glutathione conjugate shows that the contacts of the glutathione moiety with the protein are identical to those observed in crystal structures of the enzyme with other glutathione-based substrates and inhibitors. The ethacrynic acid moiety of the conjugate binds in the H site in a fashion that has not been observed in crystal structures of other glutathione-based inhibitor complexes. The crystal structures implicate Tyr 108 as an electrophilic participant in the Michael addition of glutathione to ethacrynic acid.


  • Organizational Affiliation

    Ian Porter Foundation Protein Crystallography Laboratory, St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GLUTATHIONE S-TRANSFERASE P1-1
A, B
209Homo sapiensMutation(s): 0 
Gene Names: GSTP1
EC: 2.5.1.18
UniProt & NIH Common Fund Data Resources
Find proteins for P09211 (Homo sapiens)
Explore P09211 
Go to UniProtKB:  P09211
PHAROS:  P09211
GTEx:  ENSG00000084207 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP09211
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
EAA BindingDB:  3GSS IC50: min: 3400, max: 2.60e+4 (nM) from 3 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.233 
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.657α = 90
b = 89.347β = 97.44
c = 68.596γ = 90
Software Package:
Software NamePurpose
AMoREphasing
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1997-11-12
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2011-12-14
    Changes: Non-polymer description
  • Version 1.4: 2023-08-09
    Changes: Database references, Derived calculations, Refinement description