Mutation of a critical arginine in microsomal prostaglandin e synthase-1 shifts the isomerase activity to a reductase activity that converts prostaglandin H2 into prostaglandin F2α

  • Hammarberg T
  • Hamberg M
  • Wetterholm A
 et al. 
  • 12


    Mendeley users who have this article in their library.
  • 27


    Citations of this article.


Microsomal prostaglandin E synthase type 1 (mPGES-1) converts prostaglandin endoperoxides, generated from arachidonic acid by cyclooxygenases, into prostaglandin E2. This enzyme belongs to the membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG) family of integral membrane proteins, and because of its link to inflammatory conditions and preferential coupling to cyclooxygenase 2, it has received considerable attention as a drug target. Based on the high resolution crystal structure of human leukotriene C4 synthase, a model of mPGES-1 has been constructed in which the tripeptide co-substrate glutathione is bound in a horseshoe-shaped conformation with its thiol group positioned in close proximity to Arg-126. Mutation of Arg-126 into an Ala or Gln strongly reduces the enzyme's prostaglandin E synthase activity (85-95%), whereas mutation of a neighboring Arg-122 does not have any significant effect. Interestingly, R126A and R126Q mPGES-1 exhibit a novel, glutathione-dependent, reductase activity, which allows conversion of prostaglandin H2 into prostaglandin F2alpha. Our data show that Arg-126 is a catalytic residue in mPGES-1 and suggest that MAPEG enzymes share significant structural components of their active sites.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • Tove Hammarberg

  • Mats Hamberg

  • Anders Wetterholm

  • Henrik Hansson

  • Bengt Samuelsson

  • Jesper Z. Haeggström

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free