title: Isomerization of the phytohormone precursor 12-oxophytodienoic acid (OPDA) in the insect gut: a mechanistic and computational study.
abstract: 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-[(2)H]-iso-OPDA demonstrated the complete retention of the deuterium atom in the product 11-[(2)H]-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 Δ(5)-3-ketosteroids to Δ(4)-3-ketosteroids or the conversion of prostaglandin A(1) to the biologically inactive prostaglandin B(1).
authors.affiliation: Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Hans-Knöll-Strasse 8, 07745 Jena, Germany.
authors.forename: Paulina
authors.initials: P
authors.lastname: Dabrowska
authors.forename: Mohammed
authors.initials: M
authors.lastname: Shabab
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brandt
authors.forename: Heiko
authors.initials: H
authors.lastname: Vogel
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Boland
mesh_terms: D000818:Animals; D000852:Anopheles; D055162:Biocatalysis; D020134:Catalytic Domain; D003903:Deuterium / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000737:chemistry* / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D008958:Models, Molecular; D010937:Plant Growth Regulators / Q000737:chemistry* / Q000378:metabolism*; D017385:Sequence Homology; D013237:Stereoisomerism
chemical_list: D005231:Fatty Acids, Unsaturated; D010937:Plant Growth Regulators; C025999:12-oxophytodienoic acid; D003903:Deuterium; D005982:Glutathione Transferase