Structure Determination and Refinement of Human Alpha Class Glutathione Transferase A1-1, and a Comparison With the Mu and Pi Class Enzymes

J Mol Biol. 1993 Jul 5;232(1):192-212. doi: 10.1006/jmbi.1993.1376.

Abstract

The crystal structure of human alpha class glutathione transferase A1-1 has been determined and refined to a resolution of 2.6 A. There are two copies of the dimeric enzyme in the asymmetric unit. Each monomer is built from two domains. A bound inhibitor, S-benzyl-glutathione, is primarily associated with one of these domains via a network of hydrogen bonds and salt-links. In particular, the sulphur atom of the inhibitor forms a hydrogen bond to the hydroxyl group of Tyr9 and the guanido group of Arg15. The benzyl group of the inhibitor is completely buried in a hydrophobic pocket. The structure shows an overall similarity to the mu and pi class enzymes particularly in the glutathione-binding domain". The main difference concerns the extended C terminus of the alpha class enzyme which forms an extra alpha-helix that blocks one entrance to the active site and makes up part of the substrate binding site.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography
  • Glutathione / chemistry
  • Glutathione Transferase / classification
  • Glutathione Transferase / ultrastructure*
  • Humans
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Proteins
  • Sequence Alignment
  • Software
  • X-Ray Diffraction

Substances

  • Macromolecular Substances
  • Recombinant Proteins
  • Glutathione Transferase
  • Glutathione