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PDBsum entry 1xwg

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protein Protein-protein interface(s) links
Transferase PDB id
1xwg
Jmol
Contents
Protein chain
213 a.a. *
Waters ×448
* Residue conservation analysis
PDB id:
1xwg
Name: Transferase
Title: Human gst a1-1 t68e mutant
Structure: Glutathione s-transferase a1. Chain: a, b. Synonym: gth1, ha subunit 1, gst-epsilon, gsta1-1, gst class-alpha. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
1.85Å     R-factor:   0.169     R-free:   0.218
Authors: E.Grahn,E.Jakobsson,A.Gustafsson,M.Novotny,L.Grehn,B.Olin, D.Madsen,M.Wahlberg,B.Mannervik,G.J.Kleywegt
Key ref:
E.Grahn et al. (2006). New crystal structures of human glutathione transferase A1-1 shed light on glutathione binding and the conformation of the C-terminal helix. Acta Crystallogr D Biol Crystallogr, 62, 197-207. PubMed id: 16421451 DOI: 10.1107/S0907444905039296
Date:
01-Nov-04     Release date:   01-Nov-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P08263  (GSTA1_HUMAN) -  Glutathione S-transferase A1
Seq:
Struc:
222 a.a.
213 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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
= 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  

 

 
    reference    
 
 
DOI no: 10.1107/S0907444905039296 Acta Crystallogr D Biol Crystallogr 62:197-207 (2006)
PubMed id: 16421451  
 
 
New crystal structures of human glutathione transferase A1-1 shed light on glutathione binding and the conformation of the C-terminal helix.
E.Grahn, M.Novotny, E.Jakobsson, A.Gustafsson, L.Grehn, B.Olin, D.Madsen, M.Wahlberg, B.Mannervik, G.J.Kleywegt.
 
  ABSTRACT  
 
Human glutathione transferase A1-1 is a well studied enzyme, but despite a wealth of structural and biochemical data a number of aspects of its catalytic function are still poorly understood. Here, five new crystal structures of this enzyme are described that provide several insights. Firstly, the structure of a complex of the wild-type human enzyme with glutathione was determined for the first time at 2.0 angstroms resolution. This reveals that glutathione binds in the G site in a very similar fashion as the glutathione portion of substrate analogues in other structures and also that glutathione binding alone is sufficient to stabilize the C-terminal helix of the protein. Secondly, we have studied the complex with a decarboxylated glutathione conjugate that is known to dramatically decrease the activity of the enzyme. The T68E mutant of human glutathione transferase A1-1 recovers some of the activity that is lost with the decarboxylated glutathione, but our structures of this mutant show that none of the earlier explanations of this phenomenon are likely to be correct. Thirdly, and serendipitously, the apo structures also reveal the conformation of the crucial C-terminal region that is disordered in all previous apo structures. The C-terminal region can adopt an ordered helix-like structure even in the apo state, but shows a strong tendency to unwind. Different conformations of the C-terminal regions were observed in the apo states of the two monomers, which suggests that cooperativity could play a role in the activity of the enzyme.
 
  Selected figure(s)  
 
Figure 2.
Figure 2 Crystal structure of human GST A1-1 with only glutathione bound. (a) The homodimer shown in a ribbon representation. The view is along the twofold axis that relates the two subunits. (b) The A subunit with secondary-structure elements labelled. Figs. 2, 3 and 4 were created using Swiss-PDB Viewer 3.7 (Guex & Peitsch, 1997 [Guex, N. & Peitsch, M. C. (1997). Electrophoresis, 18, 2714-2723.]) and POV-Ray 3.6 for Windows (http://www.povray.org/ ).
Figure 5.
Figure 5 Superposition of the C-terminal regions of various GST A1-1 structures. (a) Eight different GST A1-1 structures (16 monomers; PDB codes 1guh , 1gse and 1gsf , as well as the five structures reported here) were superimposed (using the C^ atoms of residues 2-209). Four structures with a glutathione conjugate bound are shown in red, the two apo structures in yellow, the structure with only glutathione bound in blue and the structure with ethacrynic acid bound in green. (b) Superposition of the C-terminal regions of the two apo structures presented here. A monomers are shown in red and B monomers in yellow. Figs. 5 and 6 were created with PyMOL (http://www.pymol.org/ ).
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2006, 62, 197-207) copyright 2006.  
  Figures were selected by an automated process.  

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
19618965 L.M.Balogh, I.Le Trong, K.A.Kripps, K.Tars, R.E.Stenkamp, B.Mannervik, and W.M.Atkins (2009).
Structural analysis of a glutathione transferase A1-1 mutant tailored for high catalytic efficiency with toxic alkenals.
  Biochemistry, 48, 7698-7704.
PDB codes: 3i69 3i6a
18792041 D.F.Dourado, P.A.Fernandes, B.Mannervik, and M.J.Ramos (2008).
Glutathione transferase: new model for glutathione activation.
  Chemistry, 14, 9591-9598.  
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.