Structural basis for detoxification and oxidative stress protection in membranes

• 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.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

membrane protein

oxidative stress

enzymology

protein structure

electron crystallography

microsomal glutathione transferase

leukotriene c-4 synthase

6 angstrom resolution

s-transferase

electron crystallography

purification

activation

substrate

superfamily

microscopy

electron crystallography

protein structure

enzymology

membrane protein

oxidative stress

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)