9GSS

HUMAN GLUTATHIONE S-TRANSFERASE P1-1, COMPLEX WITH S-HEXYL GLUTATHIONE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.97 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.194 

Starting Model: experimental
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This is version 1.4 of the entry. See complete history


Literature

The structures of human glutathione transferase P1-1 in complex with glutathione and various inhibitors at high resolution.

Oakley, A.J.Bello, M.L.Battistoni, A.Ricci, G.Rossjohn, J.Villar, H.O.Parker, M.W.

(1997) J Mol Biol 274: 84-100

  • DOI: https://doi.org/10.1006/jmbi.1997.1364
  • Primary Citation of Related Structures:  
    10GS, 5GSS, 6GSS, 7GSS, 8GSS, 9GSS

  • PubMed Abstract: 

    The human pi-class glutathione S-transferase (hGST P1-1) is a target for structure-based inhibitor design with the aim of developing drugs that could be used as adjuvants in chemotherapeutic treatment. Here we present seven crystal structures of the enzyme in complex with substrate (glutathione) and two inhibitors (S-hexyl glutathione and gamma-glutamyl- (S-benzyl)cysteinyl-D-phenylglycine). The binding of the modified glutathione inhibitor, gamma-glutamyl-(S-benzyl)cysteinyl-D-phenylglycine, has been characterized with the phenyl group stacking against the benzyl moiety of the inhibitor and making interactions with the active-site residues Phe8 and Trp38. The structure provides an explanation as to why this compound inhibits the pi-class GST much better than the other GST classes. The structure of the enzyme in complex with glutathione has been determined to high resolution (1.9 to 2.2 A) in three different crystal forms and at two different temperatures (100 and 288 K). In one crystal form, the direct hydrogen-bonding interaction between the hydroxyl group of Tyr7, a residue involved in catalysis, and the thiol group of the substrate, glutathione, is broken and replaced by a water molecule that mediates the interaction. The hydrogen-bonding partner of the hydroxyl group of Tyr108, another residue implicated in the catalysis, is space-group dependent. A high-resolution (2.0 A) structure of the enzyme in complex with S-hexyl glutathione in a new crystal form is presented. The enzyme-inhibitor complexes show that the binding of ligand into the electrophilic binding site does not lead to any conformational changes of the protein.


  • Organizational Affiliation

    The Ian Potter 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: GTP_HUMAN
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
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.97 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.194 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.774α = 90
b = 89.914β = 97.73
c = 68.751γ = 90
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling
X-PLORphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1998-09-16
    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: 2023-08-09
    Changes: Database references, Derived calculations, Other, Refinement description
  • Version 1.4: 2024-05-22
    Changes: Data collection