PDBsum entry 1bay

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Transferase PDB id
Protein chains
193 a.a. *
Waters ×150
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Glutathione s-transferase yfyf cys 47-carboxymethylated class pi, free enzyme
Structure: Glutathione s-transferase class pi. Chain: a, b. Synonym: gst yfyf. Other_details: chemical modification on cys 47 with iodoacetic acid, cys 47 carboxymethylated
Source: Mus musculus. House mouse. Organism_taxid: 10090. Organ: liver
Biol. unit: Homo-Dimer (from PDB file)
2.00Å     R-factor:   0.193     R-free:   0.236
Authors: M.C.Vega,M.Coll
Key ref:
M.C.Vega et al. (1998). The three-dimensional structure of Cys-47-modified mouse liver glutathione S-transferase P1-1. Carboxymethylation dramatically decreases the affinity for glutathione and is associated with a loss of electron density in the alphaB-310B region. J Biol Chem, 273, 2844-2850. PubMed id: 9446594 DOI: 10.1074/jbc.273.5.2844
02-Nov-96     Release date:   12-Nov-97    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P19157  (GSTP1_MOUSE) -  Glutathione S-transferase P 1
210 a.a.
193 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     TRAF2-GSTP1 complex   11 terms 
  Biological process     metabolic process   38 terms 
  Biochemical function     S-nitrosoglutathione binding     8 terms  


DOI no: 10.1074/jbc.273.5.2844 J Biol Chem 273:2844-2850 (1998)
PubMed id: 9446594  
The three-dimensional structure of Cys-47-modified mouse liver glutathione S-transferase P1-1. Carboxymethylation dramatically decreases the affinity for glutathione and is associated with a loss of electron density in the alphaB-310B region.
M.C.Vega, S.B.Walsh, T.J.Mantle, M.Coll.
The three-dimensional structure of mouse liver glutathione S-transferase P1-1 carboxymethylated at Cys-47 and its complex with S-(p-nitrobenzyl)glutathione have been determined by x-ray diffraction analysis. The structure of the modified enzyme described here is the first structural report for a Pi class glutathione S-transferase with no glutathione, glutathione S-conjugate, or inhibitor bound. It shows that part of the active site area, which includes helix alphaB and helix 310B, is disordered. However, the environment of Tyr-7, an essential residue for the catalytic reaction, remains unchanged. The position of the sulfur atom of glutathione is occupied in the ligand-free enzyme by a water molecule that is at H-bond distance from Tyr-7. We do not find any structural evidence for a tyrosinate form, and therefore our results suggest that Tyr-7 is not acting as a general base abstracting the proton from the thiol group of glutathione. The binding of the inhibitor S-(p-nitrobenzyl)-glutathione to the carboxymethylated enzyme results in a partial restructuring of the disordered area. The modification of Cys-47 sterically hinders structural organization of this region, and although it does not prevent glutathione binding, it significantly reduces the affinity. A detailed kinetic study of the modified enzyme indicates that the carboxymethylation increases the Km for glutathione by 3 orders of magnitude, although the enzyme can function efficiently under saturating conditions.
  Selected figure(s)  
Figure 2.
Fig. 2. C^ trace of the Cys-47-carboxymethylated mGST P1-1 dimer. The inhibitor S-(p-nitrobenzyl)glutathione is represented^ by pink (aromatic ring) and blue balls. The disordered zone in the unliganded CM-mGST P1-1 is shown in orange. It includes the^ external helices B and 3[10]B and affects mainly the G-subsite.
Figure 4.
Fig. 4. 2F[o] F[c] (blue) and F[o] F[c] (red) Fourier maps in the vicinity of Tyr-7 before^ assigning the residual density (superimposed red and blue globule) to water molecule W0.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (1998, 273, 2844-2850) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21134126 G.McManus, M.Costa, A.Canals, M.Coll, and T.J.Mantle (2011).
Site-directed mutagenesis of mouse glutathione transferase P1-1 unlocks masked cooperativity, introduces a novel mechanism for 'ping pong' kinetic behaviour, and provides further structural evidence for participation of a water molecule in proton abstraction from glutathione.
  FEBS J, 278, 273-281.
PDB code: 3o76
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
20941747 Y.Liu, M.He, X.Sun, K.Peng, and L.Zhao (2010).
Alteration of nuclear protein profiling for NIH-3T3 cells exposed to H₂O₂.
  Cell Biochem Funct, 28, 578-584.  
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.  
17433278 C.R.Orton, and D.C.Liebler (2007).
Analysis of protein adduction kinetics by quantitative mass spectrometry: competing adduction reactions of glutathione-S-transferase P1-1 with electrophiles.
  Chem Biol Interact, 168, 117-127.  
17405918 J.Gayarre, M.I.Avellano, F.J.Sánchez-Gómez, M.J.Carrasco, F.J.Cañada, and D.Pérez-Sala (2007).
Modification of proteins by cyclopentenone prostaglandins is differentially modulated by GSH in vitro.
  Ann N Y Acad Sci, 1096, 78-85.  
17587159 Y.Wu, J.Shen, and Z.Yin (2007).
Expression, purification and functional analysis of hexahistidine-tagged human glutathione S-transferase P1-1 and its cysteinyl mutants.
  Protein J, 26, 359-370.  
17341644 K.Stamatakis, and D.Pérez-Sala (2006).
Prostanoids with cyclopentenone structure as tools for the characterization of electrophilic lipid-protein interactomes.
  Ann N Y Acad Sci, 1091, 548-570.  
17112229 Y.M.Koen, W.Yue, N.A.Galeva, T.D.Williams, and R.P.Hanzlik (2006).
Site-specific arylation of rat glutathione s-transferase A1 and A2 by bromobenzene metabolites in vivo.
  Chem Res Toxicol, 19, 1426-1434.  
12565703 A.Pennelli, P.Sacchetta, C.Catitti, F.Amicarelli, and C.Di Ilio (2003).
Effects of glutathione on kinetics and structural properties of amphibian BbGSTP1-1.
  Int J Biochem Cell Biol, 35, 415-421.  
12192076 J.K.Luo, J.A.Hornby, L.A.Wallace, J.Chen, R.N.Armstrong, and H.W.Dirr (2002).
Impact of domain interchange on conformational stability and equilibrium folding of chimeric class micro glutathione transferases.
  Protein Sci, 11, 2208-2217.  
11604524 A.J.Oakley, T.Harnnoi, R.Udomsinprasert, K.Jirajaroenrat, A.J.Ketterman, and M.C.Wilce (2001).
The crystal structures of glutathione S-transferases isozymes 1-3 and 1-4 from Anopheles dirus species B.
  Protein Sci, 10, 2176-2185.
PDB codes: 1jlv 1jlw
9799517 J.M.Stevens, J.A.Hornby, R.N.Armstrong, and H.W.Dirr (1998).
Class sigma glutathione transferase unfolds via a dimeric and a monomeric intermediate: impact of subunit interface on conformational stability in the superfamily.
  Biochemistry, 37, 15534-15541.  
9818188 R.N.Armstrong (1998).
Mechanistic imperatives for the evolution of glutathione transferases.
  Curr Opin Chem Biol, 2, 618-623.  
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 code is shown on the right.