PDBsum entry 3i69

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Transferase PDB id
Jmol PyMol
Protein chain
(+ 2 more) 219 a.a. *
GSH ×2
Waters ×239
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Apo glutathione transferase a1-1 gimf-helix mutant
Structure: Glutathione s-transferase a1. Chain: a, b, c, d, e, f, g, h. Synonym: gth1, ha subunit 1, gst-epsilon, gsta1-1, gst clas member 1. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: gsta1. Expressed in: escherichia coli. Expression_system_taxid: 562
2.38Å     R-factor:   0.228     R-free:   0.289
Authors: L.M.Balogh,I.Le Trong,R.E.Stenkamp,W.M.Atkins
Key ref: L.M.Balogh et al. (2009). Structural analysis of a glutathione transferase A1-1 mutant tailored for high catalytic efficiency with toxic alkenals. Biochemistry, 48, 7698-7704. PubMed id: 19618965
06-Jul-09     Release date:   01-Sep-09    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P08263  (GSTA1_HUMAN) -  Glutathione S-transferase A1
222 a.a.
219 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 13 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 = 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   3 terms 
  Biological process     metabolic process   6 terms 
  Biochemical function     transferase activity     3 terms  


Biochemistry 48:7698-7704 (2009)
PubMed id: 19618965  
Structural analysis of a glutathione transferase A1-1 mutant tailored for high catalytic efficiency with toxic alkenals.
L.M.Balogh, I.Le Trong, K.A.Kripps, K.Tars, R.E.Stenkamp, B.Mannervik, W.M.Atkins.
The specificity of human glutathione transferase (GST) A1-1 is drastically altered to favor alkenal substrates in the GIMFhelix mutant designed to mimic first-sphere interactions utilized by GSTA4-4. This redesign serves as a model for improving our understanding of the structural determinants that contribute to the distinct specificities of alpha class GSTs. Herein we report the first crystal structures of GIMFhelix, both in complex with GSH and in apo form at 1.98 and 2.38 A resolution. In contrast to the preorganized hydrophobic binding pocket that accommodates alkenals in GSTA4-4, GSTA1-1 includes a dynamic alpha9 helix that undergoes a ligand-dependent localization to complete the active site. Comparisons of the GIMFhelix structures with previously reported structures show a striking similarity with the GSTA4-4 active site obtained within an essentially GSTA1-1 scaffold and reveal the alpha9 helix assumes a similar localized structure regardless of active site occupancy in a manner resembling that of GSTA4-4. However, we cannot fully account for all the structural elements important in GSTA4-4 within the mutant's active site. The contribution of Phe10 to the Tyr212-Phe10-Phe220 network prevents complete C-terminal closure and demonstrates that the presence of Phe10 within the context of a GSTA4-4-like active site may ultimately hinder Phe220, a key C-terminal residue, from effectively contributing to the active site. In total, these results illustrate the remaining structural differences presumably reflected in the previously reported catalytic efficiencies of GIMFhelix and GSTA4-4 and emphasize the F10P mutation as being necessary to completely accomplish the transformation to a highly specific GST from the more promiscuous GSTA1-1 enzyme.

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21401344 L.M.Balogh, and W.M.Atkins (2011).
Interactions of glutathione transferases with 4-hydroxynonenal.
  Drug Metab Rev, 43, 165-178.  
20085333 L.M.Balogh, I.Le Trong, K.A.Kripps, L.M.Shireman, R.E.Stenkamp, W.Zhang, B.Mannervik, and W.M.Atkins (2010).
Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4-dependent metabolism of 4-hydroxynonenal.
  Biochemistry, 49, 1541-1548.
PDB codes: 3ik7 3ik9
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