PDBsum entry 3n9j

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
Jmol PyMol
Protein chain
208 a.a.
MES ×2
EAA ×2
_CA ×3
Waters ×377
PDB id:
Name: Transferase
Title: Structure of human glutathione transferase pi class in compl ethacraplatin
Structure: Glutathione s-transferase p. Chain: a, b. Synonym: gst class-pi, gstp1-1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: faees3, gst3, gstp1. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.85Å     R-factor:   0.180     R-free:   0.218
Authors: L.J.Parker,M.W.Parker
Key ref: L.J.Parker et al. (2011). Studies of glutathione transferase P1-1 bound to a platinum(IV)-based anticancer compound reveal the molecular basis of its activation. Chemistry, 17, 7806-7816. PubMed id: 21681839
30-May-10     Release date:   11-May-11    
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Protein chains
Pfam   ArchSchema ?
P09211  (GSTP1_HUMAN) -  Glutathione S-transferase P
210 a.a.
208 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Glutathione transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RX + glutathione = HX + R-S-glutathione
+ glutathione
= 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     extracellular region   13 terms 
  Biological process     metabolic process   47 terms 
  Biochemical function     S-nitrosoglutathione binding     12 terms  


Chemistry 17:7806-7816 (2011)
PubMed id: 21681839  
Studies of glutathione transferase P1-1 bound to a platinum(IV)-based anticancer compound reveal the molecular basis of its activation.
L.J.Parker, L.C.Italiano, C.J.Morton, N.C.Hancock, D.B.Ascher, J.B.Aitken, H.H.Harris, P.Campomanes, U.Rothlisberger, A.De Luca, M.Lo Bello, W.H.Ang, P.J.Dyson, M.W.Parker.
Platinum-based cancer drugs, such as cisplatin, are highly effective chemotherapeutic agents used extensively for the treatment of solid tumors. However, their effectiveness is limited by drug resistance, which, in some cancers, has been associated with an overexpression of pi class glutathione S-transferase (GST P1-1), an important enzyme in the mercapturic acid detoxification pathway. Ethacraplatin (EA-CPT), a trans-Pt(IV) carboxylate complex containing ethacrynate ligands, was designed as a platinum cancer metallodrug that could also target cytosolic GST enzymes. We previously reported that EA-CPT was an excellent inhibitor of GST activity in live mammalian cells compared to either cisplatin or ethacrynic acid. In order to understand the nature of the drug-protein interactions between EA-CPT and GST P1-1, and to obtain mechanistic insights at a molecular level, structural and biochemical investigations were carried out, supported by molecular modeling analysis using quantum mechanical/molecular mechanical methods. The results suggest that EA-CPT preferentially docks at the dimer interface at GST P1-1 and subsequent interaction with the enzyme resulted in docking of the ethacrynate ligands at both active sites (in the H-sites), with the Pt moiety remaining bound at the dimer interface. The activation of the inhibitor by its target enzyme and covalent binding accounts for the strong and irreversible inhibition of enzymatic activity by the platinum complex.