GST_N family; microsomal Prostaglandin E synthase Type 2 (mPGES2) subfamily; mPGES2 is a membrane-anchored dimeric protein containing a CXXC motif which catalyzes the isomerization of PGH2 to PGE2. Unlike cytosolic PGE synthase (cPGES) and microsomal PGES Type 1 (mPGES1), mPGES2 does not require glutathione (GSH) for its activity, although its catalytic rate is increased two- to four-fold in the presence of DTT, GSH or other thiol compounds. PGE2 is widely distributed in various tissues and is implicated in the sleep/wake cycle, relaxation/contraction of smooth muscle, excretion of sodium ions, maintenance of body temperature and mediation of inflammation. mPGES2 contains an N-terminal hydrophobic domain which is membrane associated, and a C-terminal soluble domain with a GST-like structure.
Structure:1Z9H; Macaca fascicularis mPGES2 with bound indomethacin (IMN) and an acetate ion; contacts at 3.5A
Comment:The first cysteine of the CXXC motif is essential for the catalytic activity of mPGES2.
Comment:GRX reduces protein disulfides via a dithiol mechanism similar to that employed by TRX, where the exposed N-terminal cysteine initiates attack on the substrate disulfide followed by an intramolecular attack of the the C-terminal cysteine. GRX also uniquely reduces GSH mixed disulfides in which it utilizes only the N-terminal cysteine in a monothiol mechanism.
Jiyao W et al.(2023). "The conserved domain database in 2023.",