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PDBsum entry 1fhe

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Transferase PDB id
1fhe
Jmol
Contents
Protein chain
214 a.a. *
Ligands
GSH
Waters ×30
* Residue conservation analysis
PDB id:
1fhe
Name: Transferase
Title: Glutathione transferase (fh47) from fasciola hepatica
Structure: Glutathione transferase. Chain: a. Synonym: gst. Engineered: yes
Source: Fasciola hepatica. Liver fluke. Organism_taxid: 6192. Organ: liver. Cellular_location: cytoplasm. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: secreted as a monomer, forms membrane-bound
Biol. unit: Dimer (from PDB file)
Resolution:
3.00Å     R-factor:   0.237     R-free:   0.354
Authors: J.Rossjohn,M.W.Parker
Key ref:
J.Rossjohn et al. (1997). Crystallization, structural determination and analysis of a novel parasite vaccine candidate: Fasciola hepatica glutathione S-transferase. J Mol Biol, 273, 857-872. PubMed id: 9367777 DOI: 10.1006/jmbi.1997.1338
Date:
24-Jul-97     Release date:   29-Jul-98    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P31670  (GST27_FASHE) -  Glutathione S-transferase class-mu 26 kDa isozyme 47
Seq:
Struc:
218 a.a.
214 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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
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     cytoplasm   1 term 
  Biological process     metabolic process   1 term 
  Biochemical function     transferase activity     2 terms  

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.1997.1338 J Mol Biol 273:857-872 (1997)
PubMed id: 9367777  
 
 
Crystallization, structural determination and analysis of a novel parasite vaccine candidate: Fasciola hepatica glutathione S-transferase.
J.Rossjohn, S.C.Feil, M.C.Wilce, J.L.Sexton, T.W.Spithill, M.W.Parker.
 
  ABSTRACT  
 
Glutathione S-transferases (GSTs) represent the major class of detoxifying enzymes from parasitic helminths. As a result, they are candidates for chemotherapeutic and vaccine design. Indeed, GSTs from Fasciola hepatica have been found to be effective for vaccinating sheep and cattle against fasciolosis. This helminth contains at least seven GST isoforms, of which four have been cloned. The cloned isoforms (Fh51, Fh47, Fh7 and Fh1) all belong to the mu class of GSTs, share greater than 71% sequence identity, yet display distinct substrate specificities. Crystals of Fh47 were obtained using the hanging drop vapour diffusion technique. The crystals belong to space group I4122, with one monomer in the asymmetric unit, which corresponds to a very high solvent content of approximately 75%. The physiological dimer is generated via a crystallographic 2-fold rotation. The three-dimensional structure of Fh47 was solved by molecular replacement using the Schistosoma japonicum glutathione S-transferase (Sj26) crystal structure as a search model. The structure adopts the canonical GST fold comprising two domains: an N-terminal glutathione-binding domain, consisting of a four-stranded beta-sheet and three helices whilst the C-terminal domain is entirely alpha-helical. The presence of Phe19 in Fh47 results in a 6 degrees interdomain rotation in comparison to Sj26, where the equivalent residue is a leucine. Homology models of Fh51, Fh7 and Fh1, based on the Fh47 crystal structure, reveal critical differences in the residues lining the xenobiotic binding site, particularly at residue positions 9, 106 and 204. In addition, differences amongst the isoforms in the non-substrate binding site were noted, which may explain the observed differential binding of large ligands. The major immunogenic epitopes of Fh47 were surprisingly found not to reside on the most solvent-exposed regions of the molecule.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. Residues lining the H-sites of the FhGST isoforms. (a) Surface representation of Fh47 produced using GRASP (Nicholls et al., 1991). Red, green, blue and magenta denote negatively charged, hydrophobic, positively charged and polar residues, respectively. The CDNB.gluta- thione conjugate was superposed onto the FhGST active site using the rGST M3-3 coordinates (Ji et al., 1993). (b) Stereo view of the active site of the different isoforms. The isoforms Fh47, Fh51, Fh7 and Fh1 are coloured black, green, yellow and blue respectively. The residue numbering refers to Fh47. Drawn using MOLSCRIPT (Kraulis, 1991).
Figure 7.
Figure 7. Representation of the major and medium shared epitopes of Fh47, with the surface accessibility of each residue indicated. (a) Region A (49 to 61); (b) region B (83 to 93); and (c) region D (69 to 77).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 273, 857-872) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19619366 A.Jedeppa, O.K.Raina, S.Samanta, G.Nagar, N.Kumar, A.Varghese, S.C.Gupta, and P.S.Banerjee (2010).
Molecular cloning and characterization of a glutathione S-transferase in the tropical liver fluke, Fasciola gigantica.
  J Helminthol, 84, 55-60.  
17657508 T.Sakamoto, and T.Oikawa (2007).
Cubic crystal protein inclusions in the neodermis of the pancreatic fluke, Eurytrema pancreaticum, and Eurytrema coelomaticum.
  Parasitol Res, 101, 1393-1399.  
17641916 T.Y.Kim, J.Y.Lee, T.I.Kim, K.H.Moon, S.Y.Kang, and S.J.Hong (2007).
Molecular cloning and enzymatic characterization of a class mu glutathione S-transferase of Paragonimus westermani.
  Parasitol Res, 101, 1225-1231.  
17078019 G.Chemale, R.Morphew, J.V.Moxon, A.L.Morassuti, E.J.Lacourse, J.Barrett, D.A.Johnston, and P.M.Brophy (2006).
Proteomic analysis of glutathione transferases from the liver fluke parasite, Fasciola hepatica.
  Proteomics, 6, 6263-6273.  
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
11320322 V.Hlinková, L.Urbániková, D.Krajcíková, and J.Sevcík (2001).
Purification, crystallization and preliminary X-ray analysis of two crystal forms of ribonuclease Sa3.
  Acta Crystallogr D Biol Crystallogr, 57, 737-739.  
11093265 W.S.Valdar, and J.M.Thornton (2001).
Protein-protein interfaces: analysis of amino acid conservation in homodimers.
  Proteins, 42, 108-124.  
11264588 Y.H.Han, Y.H.Chung, T.Y.Kim, S.J.Hong, J.D.Choi, and Y.J.Chung (2001).
Crystallization of Clonorchis sinensis 26 kDa glutathione S-transferase and its fusion proteins with peptides of different lengths.
  Acta Crystallogr D Biol Crystallogr, 57, 579-581.  
  10548067 J.U.Flanagan, J.Rossjohn, M.W.Parker, P.G.Board, and G.Chelvanayagam (1999).
Mutagenic analysis of conserved arginine residues in and around the novel sulfate binding pocket of the human Theta class glutathione transferase T2-2.
  Protein Sci, 8, 2205-2212.  
9829702 J.U.Flanagan, J.Rossjohn, M.W.Parker, P.G.Board, and G.Chelvanayagam (1998).
A homology model for the human theta-class glutathione transferase T1-1.
  Proteins, 33, 444-454.  
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.