1PKW

Crystal structure of human glutathione transferase (GST) A1-1 in complex with glutathione


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.151 
  • R-Value Observed: 0.157 

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This is version 1.4 of the entry. See complete history


Literature

New crystal structures of human glutathione transferase A1-1 shed light on glutathione binding and the conformation of the C-terminal helix.

Grahn, E.Novotny, M.Jakobsson, E.Gustafsson, A.Grehn, L.Olin, B.Madsen, D.Wahlberg, M.Mannervik, B.Kleywegt, G.J.

(2006) Acta Crystallogr D Biol Crystallogr 62: 197-207

  • DOI: https://doi.org/10.1107/S0907444905039296
  • Primary Citation of Related Structures:  
    1PKW, 1PKZ, 1PL1, 1PL2, 1XWG

  • PubMed 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.


  • Organizational Affiliation

    Department of Cell and Molecular Biology, Uppsala University, Biomedical Centre, Box 596, SE-751 24 Uppsala, Sweden.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glutathione S-transferase A1
A, B
222Homo sapiensMutation(s): 1 
EC: 2.5.1.18
UniProt & NIH Common Fund Data Resources
Find proteins for P08263 (Homo sapiens)
Explore P08263 
Go to UniProtKB:  P08263
PHAROS:  P08263
GTEx:  ENSG00000243955 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08263
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.208 
  • R-Value Work: 0.151 
  • R-Value Observed: 0.157 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 99.204α = 90
b = 90.498β = 93.37
c = 51.334γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-06-22
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2011-12-07
    Changes: Non-polymer description
  • Version 1.4: 2018-03-07
    Changes: Data collection