Structural basis for detoxification and oxidative stress protection in membranes

Research output: Contribution to journalArticle

Abstract

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 mictosomal glutathione transferase 1, at 3.2 angstrom 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.

Details

Authors
  • Peter Holm
  • Priyaranjan Bhakat
  • Caroline Jegerschold
  • Nobuhiko Gyobu
  • Kaoru Mitsuoka
  • Yoshinori Fujiyoshi
  • Ralf Morgenstern
  • Hans Hebert
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biological Sciences

Keywords

  • electron crystallography, protein structure, enzymology, membrane protein, oxidative stress
Original languageEnglish
Pages (from-to)934-945
JournalJournal of Molecular Biology
Volume360
Issue number5
Publication statusPublished - 2006
Publication categoryResearch
Peer-reviewedYes