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PDBsum entry 2a2s

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
2a2s
Jmol
Contents
Protein chain
210 a.a. *
Ligands
MES ×2
GSN ×2
CO3
Metals
_CA
Waters ×527
* Residue conservation analysis
PDB id:
2a2s
Name: Transferase
Title: Crystal structure of human glutathione transferase in complex with s-nitrosoglutathione in the absence of reducing agent
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:
1.70Å     R-factor:   0.178     R-free:   0.208
Authors: L.J.Parker,C.J.Morton,J.J.Adams,M.W.Parker
Key ref:
R.Téllez-Sanz et al. (2006). Calorimetric and structural studies of the nitric oxide carrier S-nitrosoglutathione bound to human glutathione transferase P1-1. Protein Sci, 15, 1093-1105. PubMed id: 16597834 DOI: 10.1110/ps.052055206
Date:
23-Jun-05     Release date:   06-Jun-06    
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 = GSN)
matches with 90.00% similarity
= 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  

 

 
    reference    
 
 
DOI no: 10.1110/ps.052055206 Protein Sci 15:1093-1105 (2006)
PubMed id: 16597834  
 
 
Calorimetric and structural studies of the nitric oxide carrier S-nitrosoglutathione bound to human glutathione transferase P1-1.
R.Téllez-Sanz, E.Cesareo, M.Nuccetelli, A.M.Aguilera, C.Barón, L.J.Parker, J.J.Adams, C.J.Morton, M.Lo Bello, M.W.Parker, L.García-Fuentes.
 
  ABSTRACT  
 
The nitric oxide molecule (NO) is involved in many important physiological processes and seems to be stabilized by reduced thiol species, such as S-nitrosoglutathione (GSNO). GSNO binds strongly to glutathione transferases, a major superfamily of detoxifying enzymes. We have determined the crystal structure of GSNO bound to dimeric human glutathione transferase P1-1 (hGSTP1-1) at 1.4 A resolution. The GSNO ligand binds in the active site with the nitrosyl moiety involved in multiple interactions with the protein. Isothermal titration calorimetry and differential scanning calorimetry (DSC) have been used to characterize the interaction of GSNO with the enzyme. The binding of GSNO to wild-type hGSTP1-1 induces a negative cooperativity with a kinetic process concomitant to the binding process occurring at more physiological temperatures. GSNO inhibits wild-type enzyme competitively at lower temperatures but covalently at higher temperatures, presumably by S-nitrosylation of a sulfhydryl group. The C47S mutation removes the covalent modification potential of the enzyme by GSNO. These results are consistent with a model in which the flexible helix alpha2 of hGST P1-1 must move sufficiently to allow chemical modification of Cys47. In contrast to wild-type enzyme, the C47S mutation induces a positive cooperativity toward GSNO binding. The DSC results show that the thermal stability of the mutant is slightly higher than wild type, consistent with helix alpha2 forming new interactions with the other subunit. All these results suggest that Cys47 plays a key role in intersubunit cooperativity and that under certain pathological conditions S-nitrosylation of Cys47 by GSNO is a likely physiological scenario.
 
  Selected figure(s)  
 
Figure 1.
Stereo diagram of the 2F[o] -- F[c] electron density map of the hGSTP1-1 --GSNO complex at 1.4 A resolution (contoured at the 1[sigma] level). Only one conformer of the nitroso moiety is shown for clarity.
Figure 3.
ITC data for the binding of GSNO to wt-hGSTP1-1 at 35.1[deg]C. Titrations were performed in 20 mM sodium phosphate (pH 7.0), 5 mM NaCl, and 0.1 mM EDTA buffer. Raw data for the titration of enzyme (39.46 [mu]M) with 29 8-[mu]L injections of GSNO (13.95 mM). A preinjection of 1 [mu]L was performed at the beginning. (a) GSNO dilution experiment.
 
  The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (2006, 15, 1093-1105) copyright 2006.  
  Figures were selected by the author.  

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
19780048 I.Quesada-Soriano, L.J.Parker, A.Primavera, J.M.Casas-Solvas, A.Vargas-Berenguel, C.Barón, C.J.Morton, A.Paola Mazzetti, M.Lo Bello, M.W.Parker, and L.García-Fuentes (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.
PDB codes: 3hjm 3hjo 3hkr
18008069 H.Cui, J.Shen, D.Lu, T.Zhang, W.Zhang, D.Sun, and P.G.Wang (2008).
4-Aryl-1,3,2-oxathiazolylium-5-olate: a novel GST inhibitor to release JNK and activate c-Jun for cancer therapy.
  Cancer Chemother Pharmacol, 62, 509-515.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
18267127 Y.M.Go, and D.P.Jones (2008).
Redox compartmentalization in eukaryotic cells.
  Biochim Biophys Acta, 1780, 1273-1290.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.