Figure 3.

Two suggested chemical mechanisms of GSH-dependent isomerization of PGH₂ to PGE₂ by mPGES-1.²⁰⁾ (A) The thiolate of GSH could be stabilized by Arg¹²⁶ and could attack on the endoperoxide oxygen atom at the C-9 carbon of PGH₂ to produce an unstable reaction intermediate. The subsequent proton abstraction at C-9 followed by S-O bond cleavages is mediated by Asp⁴⁹, and then a carbonyl forms and the oxygen sulfur bond is broken to form PGE₂. (B) The reaction starts by proton abstraction at C-9 via Asp⁴⁹, and then a carbonyl forms and the endoperoxide is broken. The thiol of GSH functions as a proton donor to the developing C-11 oxyanion.