Isomerization of the Phytohormone Precursor 12-Oxophytodienoic Acid (OPDA) in the Insect Gut A MECHANISTIC AND COMPUTATIONAL STUDY

12-Oxophytodienoic acid (OPDA) is isomerized in the gut of herbivorous insects to tetrahydrodicranenone B (iso-OPDA). The transformation is achieved by a glutathione S-transferase present in the gut epithelium. Experiments with 9-[H-2]-iso-OPDA demonstrated the complete retention of the deuterium atom in the product 11-[H-2]-OPDA consistent with an intramolecular 1,3-hydrogen shift. Homology modeling based on the x-ray structure of a glutathione S-transferase from Anopheles gambiae revealed that the co-factor glutathione does not covalently bind to the substrate but appears to be involved in the initial deprotonation and enolization of the OPDA. The transformation resembles that of a mammalian GST-catalyzed isomerization of Delta(5)-3-ketosteroids to Delta(4)-3-ketosteroids or the conversion of prostaglandin A(1) to the biologically inactive prostaglandin B-1.