RCSB PDB - 1PGT: CRYSTAL STRUCTURE OF HUMAN GLUTATHIONE S-TRANSFERASE P1-1[V104] COMPLEXED WITH S-HEXYLGLUTATHIONE

 1PGT

CRYSTAL STRUCTURE OF HUMAN GLUTATHIONE S-TRANSFERASE P1-1[V104] COMPLEXED WITH S-HEXYLGLUTATHIONE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Work: 0.182 

Starting Model: experimental
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Ligand Structure Quality Assessment 

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Literature

Structure and function of the xenobiotic substrate-binding site and location of a potential non-substrate-binding site in a class pi glutathione S-transferase.

Ji, X.Tordova, M.O'Donnell, R.Parsons, J.F.Hayden, J.B.Gilliland, G.L.Zimniak, P.

(1997) Biochemistry 36: 9690-9702

  • DOI: https://doi.org/10.1021/bi970805s
  • Primary Citation of Related Structures:  
    1PGT, 2PGT

  • PubMed Abstract: 

    Complex structures of a naturally occurring variant of human class pi glutathione S-transferase 1-1 (hGSTP1-1) with either S-hexylglutathione or (9R,10R)-9-(S-glutathionyl)-10-hydroxy-9, 10-dihydrophenanthrene [(9R,10R)-GSPhen] have been determined at resolutions of 1.8 and 1.9 A, respectively. The crystal structures reveal that the xenobiotic substrate-binding site (H-site) is located at a position similar to that observed in class mu GST 1-1 from rat liver (rGSTM1-1). In rGSTM1-1, the H-site is a hydrophobic cavity defined by the side chains of Y6, W7, V9, L12, I111, Y115, F208, and S209. In hGSTP1-1, the cavity is approximately half hydrophobic and half hydrophilic and is defined by the side chains of Y7, F8, V10, R13, V104, Y108, N204, and G205 and five water molecules. A hydrogen bond network connects the five water molecules and the side chains of R13 and N204. V104 is positioned such that the introduction of a methyl group (the result of the V104I mutation) disturbs the H-site water structure and alters the substrate-binding properties of the isozyme. The hydroxyl group of Y7 forms a hydrogen bond (3.2 A) with the sulfur atom of the product. There is a short hydrogen bond (2.5 A) between Y108 (OH) and (9R, 10R)-GSPhen (O5), indicating the hydroxyl group of Y108 as an electrophilic participant in the addition of glutathione to epoxides. An N-(2-hydroxethyl)piperazine-N'-2-ethanesulfonic acid (HEPES) molecule is found in the cavity between beta2 and alphaI. The location and properties of this HEPES-binding site fit a possible non-substrate-binding site that is involved in noncompetitive inhibition of the enzyme.


  • Organizational Affiliation

    ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GLUTATHIONE S-TRANSFERASE
A, B
210Homo sapiensMutation(s): 0 
Gene Names: GTP_HUMAN
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
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Work: 0.182 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 79.39α = 90
b = 90.8β = 98.08
c = 69.15γ = 90
Software Package:
Software NamePurpose
AMoREphasing
GPRLSArefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted GTXClick on this verticalbar to view details

Entry History 

Deposition Data

  • Released Date: 1997-09-04 
  • Deposition Author(s): Ji, X.

Revision History  (Full details and data files)

  • Version 1.0: 1997-09-04
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-09
    Changes: Database references, Derived calculations, Refinement description
  • Version 1.4: 2023-08-30
    Changes: Data collection, Database references, Structure summary