PDBsum entry 3ik9

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Transferase PDB id
Protein chain
(+ 2 more) 219 a.a. *
BOB ×8
Waters ×59
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Human gst a1-1-gimf with gsdhn
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
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: gsta1. Expressed in: escherichia coli. Expression_system_taxid: 562
2.20Å     R-factor:   0.226     R-free:   0.279
Authors: L.M.Balogh,I.Le Trong,W.M.Atkins,R.E.Stenkamp
Key ref: L.M.Balogh et al. (2010). Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4-dependent metabolism of 4-hydroxynonenal. Biochemistry, 49, 1541-1548. PubMed id: 20085333
05-Aug-09     Release date:   23-Jun-10    
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 = BOB)
matches with 64.00% 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     cytoplasm   3 terms 
  Biological process     metabolic process   6 terms 
  Biochemical function     transferase activity     2 terms  


Biochemistry 49:1541-1548 (2010)
PubMed id: 20085333  
Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4-dependent metabolism of 4-hydroxynonenal.
L.M.Balogh, I.Le Trong, K.A.Kripps, L.M.Shireman, R.E.Stenkamp, W.Zhang, B.Mannervik, W.M.Atkins.
Conjugation to glutathione (GSH) by glutathione transferase A4-4 (GSTA4-4) is a major route of elimination for the lipid peroxidation product 4-hydroxynonenal (HNE), a toxic compound that contributes to numerous diseases. Both enantiomers of HNE are presumed to be toxic, and GSTA4-4 has negligible stereoselectivity toward them, despite its high catalytic chemospecificity for alkenals. In contrast to the highly flexible, and substrate promiscuous, GSTA1-1 isoform that has poor catalytic efficiency with HNE, GSTA4-4 has been postulated to be a rigid template that is preorganized for HNE metabolism. However, the combination of high substrate chemoselectivity and low substrate stereoselectivity is intriguing. The mechanism by which GSTA4-4 achieves this combination is important, because it must metabolize both enantiomers of HNE to efficiently detoxify the biologically formed mixture. The crystal structures of GSTA4-4 and an engineered variant of GSTA1-1 with high catalytic efficiency toward HNE, cocrystallized with a GSH-HNE conjugate analogue, demonstrate that GSTA4-4 undergoes no enantiospecific induced fit; instead, the active site residue Arg15 is ideally located to interact with the 4-hydroxyl group of either HNE enantiomer. The results reveal an evolutionary strategy for achieving biologically useful stereopromiscuity toward a toxic racemate, concomitant with high catalytic efficiency and substrate specificity toward an endogenously formed toxin.

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.  
  21401344 L.M.Balogh, and W.M.Atkins (2011).
Interactions of glutathione transferases with 4-hydroxynonenal.
  Drug Metab Rev, 43, 165-178.  
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