PDBsum entry 3hjo

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
Protein chain
209 a.a. *
GSH ×2
EAA ×2
CO3 ×2
_CA ×6
Waters ×473
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of glutathione transferase pi y108v mutant complex with the glutathione conjugate of ethacrynic acid
Structure: Glutathione s-transferase p. Chain: a, b. Synonym: gst class-pi, gstp1-1. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: gstp1. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.95Å     R-factor:   0.160     R-free:   0.210
Authors: L.J.Parker
Key ref: I.Quesada-Soriano et al. (2009). Influence of the H-site residue 108 on human glutathione transferase P1-1 ligand binding: structure-thermodynamic relationships and thermal stability. Protein Sci, 18, 2454-2470. PubMed id: 19780048
22-May-09     Release date:   22-Sep-09    
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Protein chains
Pfam   ArchSchema ?
P09211  (GSTP1_HUMAN) -  Glutathione S-transferase P
210 a.a.
209 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Glutathione transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RX + glutathione = HX + R-S-glutathione
Bound ligand (Het Group name = GSH)
corresponds exactly
= HX
+ R-S-glutathione
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     TRAF2-GSTP1 complex   9 terms 
  Biological process     metabolic process   31 terms 
  Biochemical function     S-nitrosoglutathione binding     8 terms  


Protein Sci 18:2454-2470 (2009)
PubMed id: 19780048  
Influence of the H-site residue 108 on human glutathione transferase P1-1 ligand binding: structure-thermodynamic relationships and thermal stability.
I.Quesada-Soriano, L.J.Parker, A.Primavera, J.M.Casas-Solvas, A.Vargas-Berenguel, C.Barón, C.J.Morton, A.P.Mazzetti, M.Lo Bello, M.W.Parker, L.García-Fuentes.
The effect of the Y108V mutation of human glutathione S-transferase P1-1 (hGST P1-1) on the binding of the diuretic drug ethacrynic acid (EA) and its glutathione conjugate (EASG) was investigated by calorimetric, spectrofluorimetric, and crystallographic studies. The mutation Tyr 108 --> Val resulted in a 3D-structure very similar to the wild type (wt) enzyme, where both the hydrophobic ligand binding site (H-site) and glutathione binding site (G-site) are unchanged except for the mutation itself. However, due to a slight increase in the hydrophobicity of the H-site, as a consequence of the mutation, an increase in the entropy was observed. The Y108V mutation does not affect the affinity of EASG for the enzyme, which has a higher affinity (K(d) approximately 0.5 microM) when compared with those of the parent compounds, K(d) (EA) approximately 13 microM, K(d) (GSH) approximately 25 microM. The EA moiety of the conjugate binds in the H-site of Y108V mutant in a fashion completely different to those observed in the crystal structures of the EA or EASG wt complex structures. We further demonstrate that the Delta C(p) values of binding can also be correlated with the potential stacking interactions between ligand and residues located in the binding sites as predicted from crystal structures. Moreover, the mutation does not significantly affect the global stability of the enzyme. Our results demonstrate that calorimetric measurements maybe useful in determining the preference of binding (the binding mode) for a drug to a specific site of the enzyme, even in the absence of structural information.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20540076 I.Quesada-Soriano, L.J.Parker, A.Primavera, J.Wielens, J.K.Holien, J.M.Casas-Solvas, A.Vargas-Berenguel, A.M.Aguilera, M.Nuccetelli, A.P.Mazzetti, M.L.Bello, M.W.Parker, and L.García-Fuentes (2011).
Diuretic drug binding to human glutathione transferase P1-1: potential role of Cys-101 revealed in the double mutant C47S/Y108V.
  J Mol Recognit, 24, 220-234.
PDB codes: 3km6 3kmo
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