Three-dimensional structure of class pi glutathione S-transferase from human placenta in complex with S-hexylglutathione at 2.8 A resolution

J Mol Biol. 1992 Sep 5;227(1):214-26. doi: 10.1016/0022-2836(92)90692-d.

Abstract

The three-dimensional structure of human class pi glutathione S-transferase from placenta (hGSTP1-1), a homodimeric enzyme, has been solved by Patterson search methods and refined at 2.8 A resolution to a final crystallographic R-factor of 19.6% (8.0 to 2.8 A resolution). Subunit folding topology, subunit overall structure and subunit association closely resembles the structure of porcine class pi glutathione S-transferase. The binding site of a competitive inhibitor, S-hexylglutathione, is analyzed and the locations of the binding regions for glutathione (G-site) and electrophilic substrates (H-site) are determined. The specific interactions between protein and the inhibitor's glutathione peptide are the same as those observed between glutathione sulfonate and the porcine isozyme. The H-site is located adjacent to the G-site, with the hexyl moiety lying above a segment (residues 8 to 10) connecting strand beta 1 and helix alpha A where it is in hydrophobic contact with Tyr7, Phe8, Val10, Val35 and Tyr106. Catalytic models are discussed on the basis of the molecular structure.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Crystallography
  • Fourier Analysis
  • Glutathione / analogs & derivatives*
  • Glutathione / metabolism
  • Glutathione Transferase / antagonists & inhibitors
  • Glutathione Transferase / ultrastructure*
  • Humans
  • Macromolecular Substances
  • Molecular Sequence Data
  • Particle Accelerators
  • Placenta / enzymology
  • Protein Binding
  • Protein Conformation
  • Swine

Substances

  • Macromolecular Substances
  • Glutathione Transferase
  • Glutathione
  • hexylglutathione