spacer
spacer

PDBsum entry 1zgn

Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Transferase PDB id
1zgn
Jmol
Contents
Protein chain
208 a.a. *
Ligands
MES ×2
GSH ×2
_NO ×4
Metals
_FE ×2
Waters ×242
* Residue conservation analysis
PDB id:
1zgn
Name: Transferase
Title: Crystal structure of the glutathione transferase pi in complex with dinitrosyl-diglutathionyl iron complex
Structure: Glutathione s-transferase p. Chain: a, b. Synonym: glutathione transferase pi, gst class-pi, gstp1-1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: gstp1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
Resolution:
2.10Å     R-factor:   0.182     R-free:   0.244
Authors: L.J.Parker,J.J.Adams,M.W.Parker
Key ref:
E.Cesareo et al. (2005). Nitrosylation of human glutathione transferase P1-1 with dinitrosyl diglutathionyl iron complex in vitro and in vivo. J Biol Chem, 280, 42172-42180. PubMed id: 16195232 DOI: 10.1074/jbc.M507916200
Date:
21-Apr-05     Release date:   01-Nov-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P09211  (GSTP1_HUMAN) -  Glutathione S-transferase P
Seq:
Struc:
210 a.a.
210 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.5.1.18  - Glutathione transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RX + glutathione = HX + R-S-glutathione
RX
+
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   10 terms 
  Biological process     metabolic process   31 terms 
  Biochemical function     S-nitrosoglutathione binding     8 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M507916200 J Biol Chem 280:42172-42180 (2005)
PubMed id: 16195232  
 
 
Nitrosylation of human glutathione transferase P1-1 with dinitrosyl diglutathionyl iron complex in vitro and in vivo.
E.Cesareo, L.J.Parker, J.Z.Pedersen, M.Nuccetelli, A.P.Mazzetti, A.Pastore, G.Federici, A.M.Caccuri, G.Ricci, J.J.Adams, M.W.Parker, M.L.Bello.
 
  ABSTRACT  
 
We have recently shown that dinitrosyl diglutathionyl iron complex, a possible in vivo nitric oxide (NO) donor, binds with extraordinary affinity to one of the active sites of human glutathione transferase (GST) P1-1 and triggers negative cooperativity in the neighboring subunit of the dimer. This strong interaction has also been observed in the human Mu, Alpha, and Theta GST classes, suggesting a common mechanism by which GSTs may act as intracellular NO carriers or scavengers. We present here the crystal structure of GST P1-1 in complex with the dinitrosyl diglutathionyl iron ligand at high resolution. In this complex the active site Tyr-7 coordinates to the iron atom through its phenolate group by displacing one of the GSH ligands. The crucial importance of this catalytic residue in binding the nitric oxide donor is demonstrated by site-directed mutagenesis of this residue with His, Cys, or Phe residues. The relative binding affinity for the complex is strongly reduced in all three mutants by about 3 orders of magnitude with respect to the wild type. Electron paramagnetic resonance spectroscopy studies on intact Escherichia coli cells expressing the recombinant GST P1-1 enzyme indicate that bacterial cells, in response to NO treatment, are able to form the dinitrosyl diglutathionyl iron complex using intracellular iron and GSH. We hypothesize the complex is stabilized in vivo through binding to GST P1-1.
 
  Selected figure(s)  
 
Figure 1.
FIGURE 1. Crystal structure of the GST P1-1 DNDGIC complex. A, stereo diagram of the final 2F[o] - F[c] electron density map of the DNGIC complex at 2.1 Å of resolution centered about the active site. The DNGIC ligand, GSH, and Tyr-7 were omitted from the final calculation, and the map is contoured at 0.75 . B, stereo diagram showing the coordination geometry of the active site.
Figure 2.
FIGURE 2.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 42172-42180) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20070240 V.A.Kostyuk, A.I.Potapovich, E.Cesareo, S.Brescia, L.Guerra, G.Valacchi, A.Pecorelli, I.B.Deeva, D.Raskovic, C.De Luca, S.Pastore, and L.G.Korkina (2010).
Dysfunction of glutathione s-transferase leads to excess 4-hydroxy-2-nonenal and H2O2 and impaired cytokine pattern in cultured keratinocytes and blood of vitiligo patients.
  Antioxid Redox Signal, 13, 607-620.  
19261856 C.A.Bosworth, J.C.Toledo, J.W.Zmijewski, Q.Li, and J.R.Lancaster (2009).
Dinitrosyliron complexes and the mechanism(s) of cellular protein nitrosothiol formation from nitric oxide.
  Proc Natl Acad Sci U S A, 106, 4671-4676.  
18480062 J.C.Toledo, C.A.Bosworth, S.W.Hennon, H.A.Mahtani, H.A.Bergonia, and J.R.Lancaster (2008).
Nitric oxide-induced conversion of cellular chelatable iron into macromolecule-bound paramagnetic dinitrosyliron complexes.
  J Biol Chem, 283, 28926-28933.  
18172742 M.A.Grillo, A.Lanza, and S.Colombatto (2008).
Transport of amino acids through the placenta and their role.
  Amino Acids, 34, 517-523.  
17136409 H.Lewandowska, S.Meczyńska, B.Sochanowicz, J.Sadło, and M.Kruszewski (2007).
Crucial role of lysosomal iron in the formation of dinitrosyl iron complexes in vivo.
  J Biol Inorg Chem, 12, 345-352.  
17342415 V.I.Bunik, J.V.Schloss, J.T.Pinto, G.E.Gibson, and A.J.Cooper (2007).
Enzyme-catalyzed side reactions with molecular oxygen may contribute to cell signaling and neurodegenerative diseases.
  Neurochem Res, 32, 871-891.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.