PDBsum entry 1k3l

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Transferase PDB id
Protein chain
221 a.a. *
GTX ×2
Waters ×477
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure analysis of s-hexyl-glutathione complex of glutathione transferase at 1.5 angstroms resolution
Structure: Glutathione s-transferase a1. Chain: a, b. Synonym: gsta1-1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
1.50Å     R-factor:   0.165     R-free:   0.241
Authors: I.Le Trong,R.E.Stenkamp,C.Ibarra,W.M.Atkins,E.T.Adman
Key ref:
I.Le Trong et al. (2002). 1.3-A resolution structure of human glutathione S-transferase with S-hexyl glutathione bound reveals possible extended ligandin binding site. Proteins, 48, 618-627. PubMed id: 12211029 DOI: 10.1002/prot.10162
03-Oct-01     Release date:   23-Oct-02    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P08263  (GSTA1_HUMAN) -  Glutathione S-transferase A1
222 a.a.
221 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Glutathione transferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RX + glutathione = HX + R-S-glutathione
Bound ligand (Het Group name = GTX)
matches with 76.00% 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  


DOI no: 10.1002/prot.10162 Proteins 48:618-627 (2002)
PubMed id: 12211029  
1.3-A resolution structure of human glutathione S-transferase with S-hexyl glutathione bound reveals possible extended ligandin binding site.
I.Le Trong, R.E.Stenkamp, C.Ibarra, W.M.Atkins, E.T.Adman.
Cytosolic glutathione S-transferases (GSTs) play a critical role in xenobiotic binding and metabolism, as well as in modulation of oxidative stress. Here, the high-resolution X-ray crystal structures of homodimeric human GSTA1-1 in the apo form and in complex with S-hexyl glutathione (two data sets) are reported at 1.8, 1.5, and 1.3A respectively. At this level of resolution, distinct conformations of the alkyl chain of S-hexyl glutathione are observed, reflecting the nonspecific nature of the hydrophobic substrate binding site (H-site). Also, an extensive network of ordered water, including 75 discrete solvent molecules, traverses the open subunit-subunit interface and connects the glutathione binding sites in each subunit. In the highest-resolution structure, three glycerol moieties lie within this network and directly connect the amino termini of the glutathione molecules. A search for ligand binding sites with the docking program Molecular Operating Environment identified the ordered water network binding site, lined mainly with hydrophobic residues, suggesting an extended ligand binding surface for nonsubstrate ligands, the so-called ligandin site. Finally, detailed comparison of the structures reported here with previously published X-ray structures reveal a possible reaction coordinate for ligand-dependent conformational changes in the active site and the C-terminus.
  Selected figure(s)  
Figure 4.
Figure 4. Hydrogen bonding between S-hexyl GSH, protein side-chains, and glycerol molecules. Hydrogen bonds are depicted as thick bonds emphasizing how one glutathione is connected to the other across the dimer interface, which runs roughly vertically in this figure.
Figure 6.
Figure 6. Comparison of apo [apo, this work, (purple)], ethacrynic acid with no GSH [1GSF^5 (cyan)], S-ethacrynic acid GSH [1GSE^5 (red)], S-benzyl-GSH [1GUH^4 (yellow)], and S-hexyl GSH [GTX-GST-1.3, this work,(green)], in the region around GSH showing helix 9 and helix 4 as cylinders. Only selected side-chains are shown for clarity. The cofactors are drawn in ball-and-stick, while side-chains are shown as solid frames. Short connecting chains are shown in white. S-Hexyl GSH at the lower left can be seen to differ little among the structures. Arg15 at the lower left is hydrogen bonded to Glu104 on helix 4, which lies vertically at the right. Tyr9 is directly beneath GSH and Phe10 fans out underneath Phe220, which comes from helix 9, running horizontal at the top of the figure. Phe10 in the apo structure (purple) can be seen to occupy the place that Phe220 would occupy if the helix were localized in the apo structure. Phe222 is also seen to systematically correlate with the position of Phe10 (green/yellow/red/cyan: S-hexyl-GSH/S-benzyl GSH/ethacrynic acid GSH/no GSH). Arg216 also seems to correlate somewhat, although the order of the cyan and red side-chains are interchanged relative to the Phe222 order. Leu 213 is packed against Met 208 (also shown, just behind where the conjugates lie, near where the two cylinders appear to touch). Met 208 is also loosely in contact with Phe10 (there are no atoms directly between the two side-chains, although they are 4.5 Å apart and, in all except the present work, the thermal parameters for the SD and CE are high compared to its remaining side-chain atoms). Also shown on helix 4 are Leu107, Leu108, and Val111, residues that comprise part of the H site.
  The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2002, 48, 618-627) copyright 2002.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21283550 C.Tuzmen, and B.Erman (2011).
Identification of ligand binding sites of proteins using the gaussian network model.
  PLoS One, 6, e16474.  
  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
18691867 P.Kapoli, I.A.Axarli, D.Platis, M.Fragoulaki, M.Paine, J.Hemingway, J.Vontas, and N.E.Labrou (2008).
Engineering sensitive glutathione transferase for the detection of xenobiotics.
  Biosens Bioelectron, 24, 498-503.  
16421451 E.Grahn, M.Novotny, E.Jakobsson, A.Gustafsson, L.Grehn, B.Olin, D.Madsen, M.Wahlberg, B.Mannervik, and G.J.Kleywegt (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.
PDB codes: 1pkw 1pkz 1pl1 1pl2 1xwg
15757902 H.W.Dirr, T.Little, D.C.Kuhnert, and Y.Sayed (2005).
A conserved N-capping motif contributes significantly to the stabilization and dynamics of the C-terminal region of class Alpha glutathione S-transferases.
  J Biol Chem, 280, 19480-19487.  
12637518 C.A.Ibarra, P.Chowdhury, J.W.Petrich, and W.M.Atkins (2003).
The anomalous pKa of Tyr-9 in glutathione S-transferase A1-1 catalyzes product release.
  J Biol Chem, 278, 19257-19265.  
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