PDBsum entry 1aqw

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Transferase/substrate PDB id
Jmol PyMol
Protein chain
209 a.a. *
GSH ×4
MES ×4
Waters ×351
* Residue conservation analysis
PDB id:
Name: Transferase/substrate
Title: Glutathione s-transferase in complex with glutathione
Structure: Glutathione s-transferase. Chain: a, b, c, d. Synonym: gst. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: placenta. Cellular_location: cytosol. Gene: gtp_human. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PDB file)
1.80Å     R-factor:   0.206     R-free:   0.261
Authors: L.Prade,R.Huber,T.H.Manoharan,W.E.Fahl,W.Reuter
Key ref:
L.Prade et al. (1997). Structures of class pi glutathione S-transferase from human placenta in complex with substrate, transition-state analogue and inhibitor. Structure, 5, 1287-1295. PubMed id: 9351803 DOI: 10.1016/S0969-2126(97)00281-5
03-Aug-97     Release date:   18-Mar-98    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P09211  (GSTP1_HUMAN) -  Glutathione S-transferase P
210 a.a.
209 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
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     extracellular region   13 terms 
  Biological process     metabolic process   47 terms 
  Biochemical function     S-nitrosoglutathione binding     12 terms  


DOI no: 10.1016/S0969-2126(97)00281-5 Structure 5:1287-1295 (1997)
PubMed id: 9351803  
Structures of class pi glutathione S-transferase from human placenta in complex with substrate, transition-state analogue and inhibitor.
L.Prade, R.Huber, T.H.Manoharan, W.E.Fahl, W.Reuter.
BACKGROUND: Glutathione S-transferases (GSTs) are detoxification enzymes, found in all aerobic organisms, which catalyse the conjugation of glutathione with a wide range of hydrophobic electrophilic substrates, thereby protecting the cell from serious damage caused by electrophilic compounds. GSTs are classified into five distinct classes (alpha, mu, pi, sigma and theta) by their substrate specificity and primary structure. Human GSTs are of interest because tumour cells show increased levels of expression of single classes of GSTs, which leads to drug resistance. Structural differences between classes of GST can therefore be utilised to develop new anti-cancer drugs. Many mutational and structural studies have been carried out on the mu and alpha classes of GST to elucidate the reaction mechanism, whereas knowledge about the pi class is still limited. RESULTS: We have solved the structures of the pi class GST hP1-1 in complex with its substrate, glutathione, a transition-state complex, the Meisenheimer complex, and an inhibitor, S-(rho-bromobenzyl)-glutathione, and refined them to resolutions of 1.8 A, 2.0 A and 1.9 A, respectively. All ligand molecules are well-defined in the electron density. In all three structures, an additionally bound N-morpholino-ethansulfonic acid molecule from the buffer solution was found. CONCLUSIONS: In the structure of the GST-glutathione complex, two conserved water molecules are observed, one of which hydrogen bonds directly to the sulphur atom of glutathione and the other forms hydrogen bonds with residues around the glutathione-binding site. These water molecules are absent from the structure of the Meisenheimer complex bound to GST, implicating that deprotonation of the cysteine occurs during formation of the ternary complex which involves expulsion of the inner bound water molecule. The comparison of our structures with known mu class GST structures show differences in the location of the electrophile-binding site (H-site), explaining the different substrate specificities of the two classes. Fluorescence measurements are in agreement with the position of the N-morpholino-ethansulfonic acid, close to Trp28, identifying a possible ligandin-substrate binding site.
  Selected figure(s)  
Figure 7.
Figure 7. Overlay of the active site of all three structures described in this paper. View is from the outer solvent area. Shown in green is the GST-GSH complex, in blue the GST-S-(p-bromobenzyl)-glutathione complex and in red the Meisenheimer complex bound to GST.
  The above figure is reprinted by permission from Cell Press: Structure (1997, 5, 1287-1295) copyright 1997.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21428697 A.Oakley (2011).
Glutathione transferases: a structural perspective.
  Drug Metab Rev, 43, 138-151.  
18703268 N.Kinsley, Y.Sayed, S.Mosebi, R.N.Armstrong, and H.W.Dirr (2008).
Characterization of the binding of 8-anilinonaphthalene sulfonate to rat class Mu GST M1-1.
  Biophys Chem, 137, 100-104.  
  19662104 X.Ji, A.Pal, R.Kalathur, X.Hu, Y.Gu, J.E.Saavedra, G.S.Buzard, A.Srinivasan, L.K.Keefer, and S.V.Singh (2008).
Structure-Based Design of Anticancer Prodrug PABA/NO.
  Drug Des Devel Ther, 2, 123-130.  
18232056 X.W.Bian, J.P.Xu, Y.F.Ping, Y.Wang, J.H.Chen, C.P.Xu, Y.Z.Wu, J.Wu, X.D.Zhou, Y.S.Chen, J.Q.Shi, and J.M.Wang (2008).
Unique proteomic features induced by a potential antiglioma agent, Nordy (dl-nordihydroguaiaretic acid), in glioma cells.
  Proteomics, 8, 484-494.  
16639747 R.Singh, M.A.White, K.V.Ramana, J.M.Petrash, S.J.Watowich, A.Bhatnagar, and S.K.Srivastava (2006).
Structure of a glutathione conjugate bound to the active site of aldose reductase.
  Proteins, 64, 101-110.
PDB code: 2f2k
15640152 M.Perbandt, J.Höppner, C.Betzel, R.D.Walter, and E.Liebau (2005).
Structure of the major cytosolic glutathione S-transferase from the parasitic nematode Onchocerca volvulus.
  J Biol Chem, 280, 12630-12636.
PDB codes: 1tu7 1tu8
14573868 L.A.Ralat, and R.F.Colman (2003).
Monobromobimane occupies a distinct xenobiotic substrate site in glutathione S-transferase pi.
  Protein Sci, 12, 2575-2587.  
12044179 J.Dong, P.R.Carey, Y.Wei, L.Luo, X.Lu, R.Q.Liu, and D.Dunaway-Mariano (2002).
Raman evidence for Meisenheimer complex formation in the hydrolysis reactions of 4-fluorobenzoyl- and 4-nitrobenzoyl-coenzyme A catalyzed by 4-chlorobenzoyl-coenzyme A dehalogenase.
  Biochemistry, 41, 7453-7463.  
  16233260 K.Hirota, and Y.Hanyu (2002).
Method for identification of mutant glutathione S-transferases conferring enhanced resistance to the anti-cancer drug chlorambucil.
  J Biosci Bioeng, 93, 618-621.  
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
11123923 C.Micaloni, A.P.Mazzetti, M.Nuccetelli, J.Rossjohn, W.J.McKinstry, G.Antonini, A.M.Caccuri, A.J.Oakley, G.Federici, G.Ricci, M.W.Parker, and M.Lo Bello (2000).
Valine 10 may act as a driver for product release from the active site of human glutathione transferase P1-1.
  Biochemistry, 39, 15961-15970.  
10652317 Y.V.Patskovsky, L.N.Patskovska, and I.Listowsky (2000).
The enhanced affinity for thiolate anion and activation of enzyme-bound glutathione is governed by an arginine residue of human Mu class glutathione S-transferases.
  J Biol Chem, 275, 3296-3304.
PDB code: 2gtu
9929473 C.C.Chuang, S.H.Wu, S.H.Chiou, and G.G.Chang (1999).
Homology modeling of cephalopod lens S-crystallin: a natural mutant of sigma-class glutathione transferase with diminished endogenous activity.
  Biophys J, 76, 679-690.  
10569948 H.W.Dirr, and L.A.Wallace (1999).
Role of the C-terminal helix 9 in the stability and ligandin function of class alpha glutathione transferase A1-1.
  Biochemistry, 38, 15631-15640.  
9930979 Y.V.Patskovsky, L.N.Patskovska, and I.Listowsky (1999).
Functions of His107 in the catalytic mechanism of human glutathione S-transferase hGSTM1a-1a.
  Biochemistry, 38, 1193-1202.
PDB code: 1gtu
9665696 A.J.Oakley, M.Lo Bello, G.Ricci, G.Federici, and M.W.Parker (1998).
Evidence for an induced-fit mechanism operating in pi class glutathione transferases.
  Biochemistry, 37, 9912-9917.
PDB codes: 14gs 16gs
9817846 L.Prade, R.Huber, and B.Bieseler (1998).
Structures of herbicides in complex with their detoxifying enzyme glutathione S-transferase - explanations for the selectivity of the enzyme in plants.
  Structure, 6, 1445-1452.
PDB codes: 1bx9 1bye
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.