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PDBsum entry 2hnl

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protein ligands Protein-protein interface(s) links
Transferase PDB id
2hnl
Jmol PyMol
Contents
Protein chains
202 a.a. *
Ligands
GSH ×2
Waters ×415
* Residue conservation analysis
PDB id:
2hnl
Name: Transferase
Title: Structure of the prostaglandin d synthase from the parasitic onchocerca volvulus
Structure: Glutathione s-transferase 1. Chain: a, b. Engineered: yes
Source: Onchocerca volvulus. Organism_taxid: 6282. Gene: gst1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.00Å     R-factor:   0.184     R-free:   0.234
Authors: M.Perbandt,J.Hoppner,C.Betzel,E.Liebau
Key ref:
M.Perbandt et al. (2008). Structure of the extracellular glutathione S-transferase OvGST1 from the human pathogenic parasite Onchocerca volvulus. J Mol Biol, 377, 501-511. PubMed id: 18258257 DOI: 10.1016/j.jmb.2008.01.029
Date:
13-Jul-06     Release date:   17-Jul-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P46434  (GST1_ONCVO) -  Glutathione S-transferase 1 (Fragment)
Seq:
Struc:
235 a.a.
202 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!
  Biochemical function     transferase activity     2 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2008.01.029 J Mol Biol 377:501-511 (2008)
PubMed id: 18258257  
 
 
Structure of the extracellular glutathione S-transferase OvGST1 from the human pathogenic parasite Onchocerca volvulus.
M.Perbandt, J.Höppner, C.Burmeister, K.Lüersen, C.Betzel, E.Liebau.
 
  ABSTRACT  
 
Onchocerciasis or river blindness, caused by the filarial worm Onchocerca volvulus, is the world's second leading infectious cause of blindness. In order to chronically infect the host, O. volvulus has evolved molecular strategies that influence and direct immune responses away from the modes most damaging to it. The O. volvulus GST1 (OvGST1) is a unique glutathione S-transferase (GST) in that it is a glycoprotein and possesses a signal peptide that is cleaved off in the process of maturation. The mature protein starts with a 25-amino-acid extension not present in other GSTs. In all life stages of the filarial worm, it is located directly at the parasite-host interface. Here, the OvGST1 functions as a highly specific glutathione-dependent prostaglandin D synthase (PGDS). The enzyme therefore has the potential to participate in the modulation of immune responses by contributing to the production of parasite-derived prostanoids and restraining the host's effector responses, making it a tempting target for chemotherapy and vaccine development. Here, we report the crystal structure of the OvGST1 bound to its cofactor glutathione at 2.0 A resolution. The structure reveals an overall structural homology to the haematopoietic PGDS from vertebrates but, surprisingly, also a large conformational change in the prostaglandin binding pocket. The observed differences reveal a different vicinity of the prostaglandin H(2) binding pocket that demands another prostaglandin H(2) binding mode to that proposed for the vertebrate PGDS. Finally, a putative substrate binding mode for prostaglandin H(2) is postulated based on the observed structural insights.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Ribbon diagram of the homodimeric OvGST1. β-Sheets are green and α-helices blue. The largest structural deviations between the parasitic enzyme and the human host counterpart are shown in red and concern helix α-4 and α-5.
Figure 7.
Fig. 7. Schematic drawing of the proposed binding mode of PGH[2]. The ω-chain of PGH[2] is adapted to the tunnel-like pocket 2 and stabilized by several hydrophobic interactions. The position of the cyclopentane ring of PGH[2] is stabilized by several H-bonds. Residues that are supposed to be directly involved in PGH[2] binding are highlighted by ovals and residues mediating H-bonds are highlighted as quadrangles. The isomerization reaction is initiated by the nucleophilic attack of the thiolic anion of the deprotonated GSH to the O[11] atom of PGH[2].
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 377, 501-511) copyright 2008.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21425928 J.U.Flanagan, and M.L.Smythe (2011).
Sigma-class glutathione transferases.
  Drug Metab Rev, 43, 194-214.  
18537826 E.Liebau, J.Höppner, M.Mühlmeister, C.Burmeister, K.Lüersen, M.Perbandt, C.Schmetz, D.Büttner, and N.Brattig (2008).
The secretory omega-class glutathione transferase OvGST3 from the human pathogenic parasite Onchocerca volvulus.
  FEBS J, 275, 3438-3453.  
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.

 

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