PDBsum entry 4pgt

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Transferase PDB id
Protein chain
210 a.a. *
SO4 ×2
GBX ×2
MES ×2
Waters ×427
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of hgstp1-1[v104] complexed with the gsh conjugate of (+)-anti-bpde
Structure: Protein (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. Strain: bl21 (de3) plyss. Organ: placenta. Cellular_location: cytoplasm. Gene: gtp_human. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
2.10Å     R-factor:   0.190     R-free:   0.179
Authors: X.Ji,J.Blaszczyk
Key ref:
X.Ji et al. (1999). Structure and function of residue 104 and water molecules in the xenobiotic substrate-binding site in human glutathione S-transferase P1-1. Biochemistry, 38, 10231-10238. PubMed id: 10441116 DOI: 10.1021/bi990668u
22-Mar-99     Release date:   01-Sep-99    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P09211  (GSTP1_HUMAN) -  Glutathione S-transferase P
210 a.a.
210 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Glutathione transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RX + glutathione = HX + R-S-glutathione
Bound ligand (Het Group name = GBX)
matches with 46.00% 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  


DOI no: 10.1021/bi990668u Biochemistry 38:10231-10238 (1999)
PubMed id: 10441116  
Structure and function of residue 104 and water molecules in the xenobiotic substrate-binding site in human glutathione S-transferase P1-1.
X.Ji, J.Blaszczyk, B.Xiao, R.O'Donnell, X.Hu, C.Herzog, S.V.Singh, P.Zimniak.
Two variants of human class pi glutathione (GSH) S-transferase 1-1 with either isoleucine or valine in position 104 (hGSTP1-1[I104] and hGSTP1-1[V104]) have distinct activity toward (+)-anti-7, 8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE]. To elucidate their structure-function relationship, we determined the crystal structures of the two variants in complex with GSBpd, the GSH conjugate of (+)-anti-BPDE, at 2.1 and 2.0 A resolution, respectively. The crystal structures reveal that residue 104 in the xenobiotic substrate-binding site (H-site) dictates the binding modes of the product molecule GSBpd with the following three consequences. First, the distance between the hydroxyl group of Y7 and the sulfur atom of GSBpd is 5.9 A in the hGSTP1-1[I104].GSBpd complex versus 3.2 A in the V104 variant. Second, one of the hydroxyl groups of GSBpd forms a direct hydrogen bond with R13 in hGSTP1-1[V104].GSBpd; in contrast, this hydrogen bond is not observed in the I104 complex. Third, in the hydrophilic portion of the H-site of the I104 complex, five H-site water molecules [Ji, X., et al. (1997) Biochemistry 36, 9690-9702] are observed, whereas in the V104 complex, two of the five have been displaced by the Bpd moiety of GSBpd. Although there is no direct hydrogen bond between Y108 (OH) and the hydroxyl groups of GSBpd, indirect hydrogen bonds mediated by water molecules are observed in both complexes, supporting the previously suggested role of the hydroxyl group of Y108 as an electrophilic participant in the addition of GSH to epoxides.

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.  
20069434 S.Palma, F.Novelli, L.Padua, A.Venuti, G.Prignano, L.Mariani, R.Cozzi, D.Tirindelli, and A.Testa (2010).
Interaction between glutathione-S-transferase polymorphisms, smoking habit, and HPV infection in cervical cancer risk.
  J Cancer Res Clin Oncol, 136, 1101-1109.  
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.  
17716224 J.M.Ladero, C.Martínez, J.M.Fernández, F.Martín, E.García-Martín, P.Ropero, A.Villegas, M.Díaz-Rubio, and J.A.Agúndez (2007).
Glutathione S-transferases pi1, alpha1 and micro3 genetic polymorphisms and the risk of hepatocellular carcinoma in humans.
  Pharmacogenomics, 8, 895-899.  
16886896 C.Martínez, F.Martín, J.M.Fernández, E.García-Martín, J.Sastre, M.Díaz-Rubio, J.A.Agúndez, and J.M.Ladero (2006).
Glutathione S-transferases mu 1, theta 1, pi 1, alpha 1 and mu 3 genetic polymorphisms and the risk of colorectal and gastric cancers in humans.
  Pharmacogenomics, 7, 711-718.  
16501997 M.Bauer, O.Herbarth, G.Aust, J.G.Hengstler, A.Dotzauer, C.Graebsch, and E.Schmuecking (2006).
Expression patterns and novel splicing variants of glutathione-S-transferase isoenzymes of human lung and hepatocyte cell lines.
  Cell Tissue Res, 324, 423-432.  
17077089 Y.S.Yun, W.Lee, S.Shin, B.H.Oh, and K.Y.Choi (2006).
Arg-158 is critical in both binding the substrate and stabilizing the transition-state oxyanion for the enzymatic reaction of malonamidase E2.
  J Biol Chem, 281, 40057-40064.  
15808397 F.F.Parl (2005).
Glutathione S-transferase genotypes and cancer risk.
  Cancer Lett, 221, 123-129.  
15115915 C.Flamant, A.Henrion-Caude, P.Y.Boëlle, F.Brémont, J.Brouard, B.Delaisi, J.F.Duhamel, C.Marguet, M.Roussey, M.C.Miesch, M.Boulé, R.C.Strange, and A.Clement (2004).
Glutathione-S-transferase M1, M3, P1 and T1 polymorphisms and severity of lung disease in children with cystic fibrosis.
  Pharmacogenetics, 14, 295-301.  
12360105 T.M.Ishimoto, and F.Ali-Osman (2002).
Allelic variants of the human glutathione S-transferase P1 gene confer differential cytoprotection against anticancer agents in Escherichia coli.
  Pharmacogenetics, 12, 543-553.  
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
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
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.