Structural basis for detoxification and oxidative stress protection in membranes

J Mol Biol. 2006 Jul 28;360(5):934-45. doi: 10.1016/j.jmb.2006.05.056. Epub 2006 Jun 5.


Synthesis of mediators of fever, pain and inflammation as well as protection against reactive molecules and oxidative stress is a hallmark of the MAPEG superfamily (membrane associated proteins in eicosanoid and glutathione metabolism). The structure of a MAPEG member, rat microsomal glutathione transferase 1, at 3.2 A resolution, solved here in complex with glutathione by electron crystallography, defines the active site location and a cytosolic domain involved in enzyme activation. The glutathione binding site is found to be different from that of the canonical soluble glutathione transferases. The architecture of the homotrimer supports a catalytic mechanism involving subunit interactions and reveals both cytosolic and membraneous substrate entry sites, providing a rationale for the membrane location of the enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Catalytic Domain
  • Conserved Sequence
  • Dimerization
  • Glutathione / chemistry
  • Glutathione / metabolism
  • Glutathione Transferase / chemistry*
  • Glutathione Transferase / metabolism
  • Inactivation, Metabolic
  • Intracellular Membranes / enzymology*
  • Lipid Bilayers / chemistry*
  • Microsomes, Liver / enzymology
  • Models, Molecular*
  • Molecular Sequence Data
  • Oxidative Stress*
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Rats
  • Sequence Homology, Amino Acid


  • Lipid Bilayers
  • Protein Subunits
  • microsomal glutathione S-transferase-I
  • Glutathione Transferase
  • Glutathione

Associated data

  • PDB/2H8A