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PDBsum entry 22gs

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protein ligands Protein-protein interface(s) links
Transferase PDB id
22gs
Jmol
Contents
Protein chain
208 a.a. *
Ligands
MES ×3
Waters ×312
* Residue conservation analysis
PDB id:
22gs
Name: Transferase
Title: Human glutathione s-transferase p1-1 y49f mutant
Structure: Glutathione s-transferase p1-1. Chain: a, b. Synonym: gst. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cellular_location: cytoplasm. Gene: gstp1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Homo-Dimer (from PDB file)
Resolution:
1.90Å     R-factor:   0.206     R-free:   0.230
Authors: A.J.Oakley
Key ref:
E.Ortiz-Salmerón et al. (2003). Thermodynamic description of the effect of the mutation Y49F on human glutathione transferase P1-1 in binding with glutathione and the inhibitor S-hexylglutathione. J Biol Chem, 278, 46938-46948. PubMed id: 12937169 DOI: 10.1074/jbc.M305043200
Date:
10-Mar-98     Release date:   23-Mar-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P09211  (GSTP1_HUMAN) -  Glutathione S-transferase P
Seq:
Struc:
210 a.a.
208 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.2.5.1.18  - Glutathione transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RX + glutathione = HX + R-S-glutathione
RX
+ 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     TRAF2-GSTP1 complex   10 terms 
  Biological process     metabolic process   31 terms 
  Biochemical function     S-nitrosoglutathione binding     8 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M305043200 J Biol Chem 278:46938-46948 (2003)
PubMed id: 12937169  
 
 
Thermodynamic description of the effect of the mutation Y49F on human glutathione transferase P1-1 in binding with glutathione and the inhibitor S-hexylglutathione.
E.Ortiz-Salmerón, M.Nuccetelli, A.J.Oakley, M.W.Parker, M.Lo Bello, L.García-Fuentes.
 
  ABSTRACT  
 
The thermodynamics of binding of both the substrate glutathione (GSH) and the competitive inhibitor S-hexylglutathione to the mutant Y49F of human glutathione S-transferase (hGST P1-1), a key residue at the dimer interface, has been investigated by isothermal titration calorimetry and fluorescence spectroscopy. Calorimetric measurements indicated that the binding of these ligands to both the Y49F mutant and wild-type enzyme is enthalpically favorable and entropically unfavorable over the temperature range studied. The affinity of these ligands for the Y49F mutant is lower than those for the wild-type enzyme due mainly to an entropy change. Therefore, the thermodynamic effect of this mutation is to decrease the entropy loss due to binding. Calorimetric titrations in several buffers with different ionization heat amounts indicate a release of protons when the mutant binds GSH, whereas protons are taken up in binding S-hexylglutathione at pH 6.5. This suggests that the thiol group of GSH releases protons to buffer media during binding and a group with low pKa (such as Asp98) is responsible for the uptake of protons. The temperature dependence of the free energy of binding, DeltaG0, is weak because of the enthalpy-entropy compensation caused by a large heat capacity change. The heat capacity change is -199.5 +/- 26.9 cal K-1 mol-1 for GSH binding and -333.6 +/- 28.8 cal K-1 mol-1 for S-hexylglutathione binding. The thermodynamic parameters are consistent with the mutation Tyr49 --> Phe, producing a slight conformational change in the active site.
 
  Selected figure(s)  
 
Figure 1.
FIG. 1. Schematic representation of the binding site of GSH (G-site) in homodimeric hGST P1-1. Subunits are displayed in green and blue. The GSH molecule is shown in a ball-and-stick representation. Helix [2] is denoted, and residues from this helix and its flanking region that directly contact GSH are also shown. Some residues of the adjacent subunit that also participate in the active site are indicated. This figure was made using VMD software (49) and corresponds to entry 7GSS [PDB] of the Protein Data Bank (3).
Figure 7.
FIG. 7. Stereoview of the region in hGST P1-1 about the site of mutation. The -carbon trace of the Y49F crystal structure is shown in light gray, and the wild-type crystal structure is shown in black (5GSS [PDB] ) (3). This figure was produced using MOLSCRIPT (50).
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 46938-46948) copyright 2003.  
  Figures were selected by an automated process.  

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
16597834 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, and L.García-Fuentes (2006).
Calorimetric and structural studies of the nitric oxide carrier S-nitrosoglutathione bound to human glutathione transferase P1-1.
  Protein Sci, 15, 1093-1105.
PDB codes: 2a2r 2a2s
15384176 M.J.Cliff, A.Gutierrez, and J.E.Ladbury (2004).
A survey of the year 2003 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 17, 513-523.  
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.