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PDBsum entry 1m0u

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1m0u
Jmol
Contents
Protein chains
203 a.a. *
Ligands
SO4 ×2
GSH
Waters ×304
* Residue conservation analysis
PDB id:
1m0u
Name: Transferase
Title: Crystal structure of the drosophila glutathione s-transferas complex with glutathione
Structure: Gst2 gene product. Chain: a, b. Synonym: glutathione s-transferase-2. Engineered: yes
Source: Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PQS)
Resolution:
1.75Å     R-factor:   0.215     R-free:   0.232
Authors: B.Agianian,P.A.Tucker,A.Schouten,K.Leonard,B.Bullard,P.Gros
Key ref:
B.Agianian et al. (2003). Structure of a Drosophila sigma class glutathione S-transferase reveals a novel active site topography suited for lipid peroxidation products. J Mol Biol, 326, 151-165. PubMed id: 12547198 DOI: 10.1016/S0022-2836(02)01327-X
Date:
14-Jun-02     Release date:   11-Feb-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P41043  (GST1_DROME) -  Glutathione S-transferase S1
Seq:
Struc:
249 a.a.
203 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     cellular_component   1 term 
  Biological process     metabolic process   4 terms 
  Biochemical function     transferase activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0022-2836(02)01327-X J Mol Biol 326:151-165 (2003)
PubMed id: 12547198  
 
 
Structure of a Drosophila sigma class glutathione S-transferase reveals a novel active site topography suited for lipid peroxidation products.
B.Agianian, P.A.Tucker, A.Schouten, K.Leonard, B.Bullard, P.Gros.
 
  ABSTRACT  
 
Insect glutathione-S-transferases (GSTs) are grouped in three classes, I, II and recently III; class I (Delta class) enzymes together with class III members are implicated in conferring resistance to insecticides. Class II (Sigma class) GSTs, however, are poorly characterized and their exact biological function remains elusive. Drosophila glutathione S-transferase-2 (GST-2) (DmGSTS1-1) is a class II enzyme previously found associated specifically with the insect indirect flight muscle. It was recently shown that GST-2 exhibits considerable conjugation activity for 4-hydroxynonenal (4-HNE), a lipid peroxidation product, raising the possibility that it has a major anti-oxidant role in the flight muscle. Here, we report the crystal structure of GST-2 at 1.75A resolution. The GST-2 dimer shows the canonical GST fold with glutathione (GSH) ordered in only one of the two binding sites. While the GSH-binding mode is similar to other GST structures, a distinct orientation of helix alpha6 creates a novel electrophilic substrate-binding site (H-site) topography, largely flat and without a prominent hydrophobic-binding pocket, which characterizes the H-sites of other GSTs. The H-site displays directionality in the distribution of charged/polar and hydrophobic residues creating a binding surface that explains the selectivity for amphipolar peroxidation products, with the polar-binding region formed by residues Y208, Y153 and R145 and the hydrophobic-binding region by residues V57, A59, Y211 and the C-terminal V249. A structure-based model of 4-HNE binding is presented. The model suggest that residues Y208, R145 and possibly Y153 may be key residues involved in catalysis.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Structure of GST-2. (a) The GST-2 dimer viewed down the 2-fold axis. The N and C termini are indicated. The GSH molecule bound to monomer A is shown in ball and stick representation. (b) Monomer A in a ribbon diagram illustrating the secondary structure elements and the bound GSH molecule. Helices are colored green, b-strands magenta and 3[10] helices gold. Naming follows standard nomenclature from other GST structures.
Figure 6.
Figure 6. Model of 4-HNE binding to GST-2. A sticks representation of the GS-HNE conjugate in a putative-binding position in the GST-2 active site is shown (for details see the text). Surface patch coloring: green, hydrophobic side-chains; magenta, tyrosine hydroxyls; blue, guanidino group; cyan, hydroxyl of the catalytic tyrosine Y54. The surface corresponding to the side-chain carbon atoms of Y153 and Y211 is not colored for clarity.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 326, 151-165) copyright 2003.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21323601 A.J.Ketterman, C.Saisawang, and J.Wongsantichon (2011).
Insect glutathione transferases.
  Drug Metab Rev, 43, 253-265.  
  21425928 J.U.Flanagan, and M.L.Smythe (2011).
Sigma-class glutathione transferases.
  Drug Metab Rev, 43, 194-214.  
21253607 M.S.Clark, M.A.Thorne, J.Y.Toullec, Y.Meng, l.e. .L.Guan, L.S.Peck, and S.Moore (2011).
Antarctic krill 454 pyrosequencing reveals chaperone and stress transcriptome.
  PLoS One, 6, e15919.  
19819328 H.C.Kuiper, B.L.Langsdorf, C.L.Miranda, J.Joss, C.Jubert, J.E.Mata, and J.F.Stevens (2010).
Quantitation of mercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites in a smoking cessation study.
  Free Radic Biol Med, 48, 65-72.  
20663851 L.Federici, M.Masulli, C.Di Ilio, and N.Allocati (2010).
Characterization of the hydrophobic substrate-binding site of the bacterial beta class glutathione transferase from Proteus mirabilis.
  Protein Eng Des Sel, 23, 743-750.  
18442969 H.C.Kuiper, C.L.Miranda, J.D.Sowell, and J.F.Stevens (2008).
Mercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites are in vivo markers of oxidative stress.
  J Biol Chem, 283, 17131-17138.  
17435007 H.K.Ledford, B.L.Chin, and K.K.Niyogi (2007).
Acclimation to singlet oxygen stress in Chlamydomonas reinhardtii.
  Eukaryot Cell, 6, 919-930.  
17284839 K.Yamamoto, H.Fujii, Y.Aso, Y.Banno, and K.Koga (2007).
Expression and characterization of a sigma-class glutathione S-transferase of the fall webworm, Hyphantria cunea.
  Biosci Biotechnol Biochem, 71, 553-560.  
20307234 O.Mittapalli, J.J.Neal, and R.H.Shukle (2007).
Tissue and life stage specificity of glutathione S-transferase expression in the Hessian fly, Mayetiola destructor: implications for resistance to host allelochemicals.
  J Insect Sci, 7, 1.  
15663770 A.A.Enayati, H.Ranson, and J.Hemingway (2005).
Insect glutathione transferases and insecticide resistance.
  Insect Mol Biol, 14, 3-8.  
16189827 D.J.Schuller, Q.Liu, I.A.Kriksunov, A.M.Campbell, J.Barrett, P.M.Brophy, and Q.Hao (2005).
Crystal structure of a new class of glutathione transferase from the model human hookworm nematode Heligmosomoides polygyrus.
  Proteins, 61, 1024-1031.
PDB code: 1tw9
15373810 J.N.Tarnay, F.Szeri, A.Iliás, T.Annilo, C.Sung, O.Le Saux, A.Váradi, M.Dean, C.D.Boyd, and S.Robinow (2004).
The dMRP/CG6214 gene of Drosophila is evolutionarily and functionally related to the human multidrug resistance-associated protein family.
  Insect Mol Biol, 13, 539-548.  
15236740 K.Ginalski, L.Kinch, L.Rychlewski, and N.V.Grishin (2004).
DCC proteins: a novel family of thiol-disulfide oxidoreductases.
  Trends Biochem Sci, 29, 339-342.  
14987763 Y.Takada, K.Uda, K.Kawamura, and T.Matsuoka (2004).
Molecular cloning and characterization of a novel glutathione S-transferase gene induced by light stimulation in the protozoan Blepharisma japonicum.
  FEMS Microbiol Lett, 231, 185-189.  
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.