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PDBsum entry 2pgt
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protein ligands Protein-protein interface(s) links
Transferase PDB id
2pgt

 

 

 

 

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Contents
Protein chain
210 a.a. *
Ligands
SO4
GPR ×2
EPE ×2
Waters ×344
* Residue conservation analysis
PDB id:
2pgt
Name: Transferase
Title: Crystal structure of human glutathione s-transferase p1-1[v104] complexed with (9r,10r)-9-(s-glutathionyl)-10-hydroxy-9,10- dihydrophenanthrene
Structure: Glutathione s-transferase. Chain: a, b. Synonym: gst, hgstp1-1[v104]. Engineered: yes. Mutation: yes. Other_details: hgstp1-1[v104] and hgstp1-1[i104] are naturally occurring variants of hgstp1-1 obtained by site-directed mutagenesis
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: 293. Organ: placenta. Cellular_location: cytoplasm. Gene: gtp_human. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
1.90Å     R-factor:   0.183    
Authors: X.Ji
Key ref:
X.Ji et al. (1997). Structure and function of the xenobiotic substrate-binding site and location of a potential non-substrate-binding site in a class pi glutathione S-transferase. Biochemistry, 36, 9690-9702. PubMed id: 9245401 DOI: 10.1021/bi970805s
Date:
17-Feb-97     Release date:   04-Sep-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P09211  (GSTP1_HUMAN) -  Glutathione S-transferase P from Homo sapiens
Seq:
Struc: 		210 a.a.
210 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 = an S-substituted glutathione + a halide anion + H+
RX
Bound ligand (Het Group name = GPR)
matches with 57.14% similarity 		+ glutathione
 = S-substituted glutathione
 + halide anion
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1021/bi970805s Biochemistry 36:9690-9702 (1997)
PubMed id: 9245401  
 
 
Structure and function of the xenobiotic substrate-binding site and location of a potential non-substrate-binding site in a class pi glutathione S-transferase.
X.Ji, M.Tordova, R.O'Donnell, J.F.Parsons, J.B.Hayden, G.L.Gilliland, P.Zimniak.
 
  ABSTRACT  
 
Complex structures of a naturally occurring variant of human class pi glutathione S-transferase 1-1 (hGSTP1-1) with either S-hexylglutathione or (9R,10R)-9-(S-glutathionyl)-10-hydroxy-9, 10-dihydrophenanthrene [(9R,10R)-GSPhen] have been determined at resolutions of 1.8 and 1.9 A, respectively. The crystal structures reveal that the xenobiotic substrate-binding site (H-site) is located at a position similar to that observed in class mu GST 1-1 from rat liver (rGSTM1-1). In rGSTM1-1, the H-site is a hydrophobic cavity defined by the side chains of Y6, W7, V9, L12, I111, Y115, F208, and S209. In hGSTP1-1, the cavity is approximately half hydrophobic and half hydrophilic and is defined by the side chains of Y7, F8, V10, R13, V104, Y108, N204, and G205 and five water molecules. A hydrogen bond network connects the five water molecules and the side chains of R13 and N204. V104 is positioned such that the introduction of a methyl group (the result of the V104I mutation) disturbs the H-site water structure and alters the substrate-binding properties of the isozyme. The hydroxyl group of Y7 forms a hydrogen bond (3.2 A) with the sulfur atom of the product. There is a short hydrogen bond (2.5 A) between Y108 (OH) and (9R, 10R)-GSPhen (O5), indicating the hydroxyl group of Y108 as an electrophilic participant in the addition of glutathione to epoxides. An N-(2-hydroxethyl)piperazine-N'-2-ethanesulfonic acid (HEPES) molecule is found in the cavity between beta2 and alphaI. The location and properties of this HEPES-binding site fit a possible non-substrate-binding site that is involved in noncompetitive inhibition of the enzyme.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21384452 A.F.Thévenin, C.L.Zony, B.J.Bahnson, and R.F.Colman (2011).
GSTpi modulates JNK activity through a direct interaction with JNK substrate, ATF2.
  Protein Sci, 20, 834-848.  
  21428697 A.Oakley (2011).
Glutathione transferases: a structural perspective.
  Drug Metab Rev, 43, 138-151.  
  21351850 K.D.Tew, and D.M.Townsend (2011).
Regulatory functions of glutathione S-transferase P1-1 unrelated to detoxification.
  Drug Metab Rev, 43, 179-193.  
18990698 D.M.Townsend, Y.Manevich, L.He, S.Hutchens, C.J.Pazoles, and K.D.Tew (2009).
Novel role for glutathione S-transferase pi. Regulator of protein S-Glutathionylation following oxidative and nitrosative stress.
  J Biol Chem, 284, 436-445.  
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.  
18796433 Y.C.Huang, S.Misquitta, S.Y.Blond, E.Adams, and R.F.Colman (2008).
Catalytically Active Monomer of Glutathione S-Transferase {pi} and Key Residues Involved in the Electrostatic Interaction between Subunits.
  J Biol Chem, 283, 32880-32888.  
17915350 G.Cornilescu, E.B.Hadley, M.G.Woll, J.L.Markley, S.H.Gellman, and C.C.Cornilescu (2007).
Solution structure of a small protein containing a fluorinated side chain in the core.
  Protein Sci, 16, 2089.  
16760134 S.N.Pandey, M.Jain, P.Nigam, G.Choudhuri, and B.Mittal (2006).
Genetic polymorphisms in GSTM1, GSTT1, GSTP1, GSTM3 and the susceptibility to gallbladder cancer in North India.
  Biomarkers, 11, 250-261.  
16008560 W.G.Willmore, and K.B.Storey (2005).
Purification and properties of the glutathione S-transferases from the anoxia-tolerant turtle, Trachemys scripta elegans.
  FEBS J, 272, 3602-3614.  
15347687 L.A.Ralat, and R.F.Colman (2004).
Glutathione S-transferase Pi has at least three distinguishable xenobiotic substrate sites close to its glutathione-binding site.
  J Biol Chem, 279, 50204-50213.  
15234974 L.Tao, and A.L.Harris (2004).
Biochemical requirements for inhibition of Connexin26-containing channels by natural and synthetic taurine analogs.
  J Biol Chem, 279, 38544-38554.  
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.  
11738048 J.Blaszczyk, J.E.Tropea, M.Bubunenko, K.M.Routzahn, D.S.Waugh, D.L.Court, and X.Ji (2001).
Crystallographic and modeling studies of RNase III suggest a mechanism for double-stranded RNA cleavage.
  Structure, 9, 1225-1236.
PDB codes: 1i4s 1jfz
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.  
10681528 J.Wang, S.Bauman, and R.F.Colman (2000).
Probing subunit interactions in alpha class rat liver glutathione S-transferase with the photoaffinity label glutathionyl S-[4-(succinimidyl)benzophenone].
  J Biol Chem, 275, 5493-5503.  
11027134 Y.Gu, S.V.Singh, and X.Ji (2000).
Residue R216 and catalytic efficiency of a murine class alpha glutathione S-transferase toward benzo[a]pyrene 7(R),8(S)-diol 9(S), 10(R)-epoxide.
  Biochemistry, 39, 12552-12557.
PDB codes: 1f3a 1f3b
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.  
10403654 P.Zimniak, S.Pikula, J.Bandorowicz-Pikula, and Y.C.Awasthi (1999).
Mechanisms for xenobiotic transport in biological membranes.
  Toxicol Lett, 106, 107-118.  
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
  9792095 D.Mandelman, F.P.Schwarz, H.Li, and T.L.Poulos (1998).
The role of quaternary interactions on the stability and activity of ascorbate peroxidase.
  Protein Sci, 7, 2089-2098.  
9843371 J.Wang, S.Bauman, and R.F.Colman (1998).
Photoaffinity labeling of rat liver glutathione S-transferase, 4-4, by glutathionyl S-[4-(succinimidyl)-benzophenone].
  Biochemistry, 37, 15671-15679.  
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 codes are shown on the right.

 

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