Identification of mu-class glutathione transferases M2-2 and M3-3 as cytosolic prostaglandin E synthases in the human brain

Neurochem Res. 2000 May;25(5):733-8. doi: 10.1023/a:1007579507804.


Cytosolic prostaglandin (PG) E synthase was purified from human brain cortex. The N-terminal amino acid sequence, PMTLGYXNIRGL, was identical to that of the human mu-class glutathione transferase (GST) M2 subunit. Complementary DNAs for human GSTM2, GSTM3, and GSTM4 subunits were cloned, and recombinant proteins were expressed as homodimers in Escherichia coli. The recombinant GSTM2-2 and 3-3 catalyzed the conversion of PGH2 to PGE2 at the rates of 282 and 923 nmol/min/mg of protein, respectively, at the optimal pH of 8, whereas GSTM4-4 was inactive; although all three enzymes showed GST activity. The PGE synthase activity depended on thiols, such as glutathione, dithiothreitol, 2-mercaptoethanol, or L-cysteine. Michaelis-Menten constants and turnover numbers for PGH2 were 141 microM and 10.8 min(-1) for GSTM2-2 and 1.5 mM and 130 min(-1) for GSTM3-3, respectively. GSTM2-2 and 3-3 may play crucial roles in temperature regulation, nociception, and sleep-wake regulation by producing PGE2 in the brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cerebral Cortex / enzymology*
  • Cloning, Molecular
  • Cytosol / enzymology
  • Glutathione Transferase / chemistry
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism*
  • Humans
  • Intramolecular Oxidoreductases / chemistry
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / metabolism*
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Kinetics
  • Peptide Fragments / chemistry
  • Prostaglandin-E Synthases
  • Protein Subunits
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Substrate Specificity
  • Sulfhydryl Compounds / metabolism


  • Isoenzymes
  • Peptide Fragments
  • Protein Subunits
  • Recombinant Proteins
  • Sulfhydryl Compounds
  • Glutathione Transferase
  • glutathione S-transferase Mu 2
  • glutathione transferase M3-3
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases