1ZGN

Crystal Structure of the Glutathione Transferase Pi in Complex with Dinitrosyl-diglutathionyl Iron Complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.182 

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This is version 1.5 of the entry. See complete history


Literature

Nitrosylation of human glutathione transferase P1-1 with dinitrosyl diglutathionyl iron complex in vitro and in vivo

Cesareo, E.Parker, L.J.Pedersen, J.Z.Nuccetelli, M.Mazzetti, A.P.Pastore, A.Federici, G.Caccuri, A.M.Ricci, G.Adams, J.J.Parker, M.W.Bello, M.L.

(2005) J Biol Chem 280: 42172-42180

  • DOI: https://doi.org/10.1074/jbc.M507916200
  • Primary Citation of Related Structures:  
    1ZGN

  • PubMed Abstract: 

    We have recently shown that dinitrosyl diglutathionyl iron complex, a possible in vivo nitric oxide (NO) donor, binds with extraordinary affinity to one of the active sites of human glutathione transferase (GST) P1-1 and triggers negative cooperativity in the neighboring subunit of the dimer. This strong interaction has also been observed in the human Mu, Alpha, and Theta GST classes, suggesting a common mechanism by which GSTs may act as intracellular NO carriers or scavengers. We present here the crystal structure of GST P1-1 in complex with the dinitrosyl diglutathionyl iron ligand at high resolution. In this complex the active site Tyr-7 coordinates to the iron atom through its phenolate group by displacing one of the GSH ligands. The crucial importance of this catalytic residue in binding the nitric oxide donor is demonstrated by site-directed mutagenesis of this residue with His, Cys, or Phe residues. The relative binding affinity for the complex is strongly reduced in all three mutants by about 3 orders of magnitude with respect to the wild type. Electron paramagnetic resonance spectroscopy studies on intact Escherichia coli cells expressing the recombinant GST P1-1 enzyme indicate that bacterial cells, in response to NO treatment, are able to form the dinitrosyl diglutathionyl iron complex using intracellular iron and GSH. We hypothesize the complex is stabilized in vivo through binding to GST P1-1.


  • Organizational Affiliation

    Department of Biology, Chemical Sciences, and Technologies, and Internal Medicine, University of Rome "Tor Vergata," 00133 Rome, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glutathione S-transferase P
A, B
209Homo sapiensMutation(s): 0 
Gene Names: GSTP1
EC: 2.5.1.18
UniProt & NIH Common Fund Data Resources
Find proteins for P09211 (Homo sapiens)
Explore P09211 
Go to UniProtKB:  P09211
PHAROS:  P09211
GTEx:  ENSG00000084207 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP09211
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
GSH
Query on GSH

Download Ideal Coordinates CCD File 
E [auth A],
J [auth B]
GLUTATHIONE
C10 H17 N3 O6 S
RWSXRVCMGQZWBV-WDSKDSINSA-N
MES
Query on MES

Download Ideal Coordinates CCD File 
D [auth A],
I [auth B]
2-(N-MORPHOLINO)-ETHANESULFONIC ACID
C6 H13 N O4 S
SXGZJKUKBWWHRA-UHFFFAOYSA-N
FE
Query on FE

Download Ideal Coordinates CCD File 
C [auth A],
H [auth B]
FE (III) ION
Fe
VTLYFUHAOXGGBS-UHFFFAOYSA-N
NO
Query on NO

Download Ideal Coordinates CCD File 
F [auth A],
G [auth A],
K [auth B],
L [auth B]
NITRIC OXIDE
N O
ODUCDPQEXGNKDN-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.182 
  • R-Value Observed: 0.182 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 76.219α = 90
b = 89.759β = 97.632
c = 68.713γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-11-01
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2024-03-13
    Changes: Data collection, Database references, Derived calculations
  • Version 1.5: 2024-03-20
    Changes: Source and taxonomy, Structure summary