Crystal structure of juvenile hormone epoxide hydrolase from the silkwormBombyx mori

The juvenile hormone (JH) is a kind of epoxidecontaining sesquiterpene ester secreted by a pair of corpora allatum behind the brain of insects.1 It controls the metamorphosis development of insects together with the ecdysone.2,3 Thus the synthesis and degradation of JH are tightly regulated in different development stages.4 The degradation of JH is catalyzed by two hydrolases, juvenile hormone epoxide hydrolase (JHEH) and juvenile hormone esterase. JHEH is responsible for opening the epoxide ring of JH to produce JH diol, whereas JHE catalyzes the removal of the methyl ester moiety of JH to form JH acid.5,6 JHEH belongs to the microsomal epoxide hydrolase (mEH) (EC 3.3.2.9) family, which is one of the most widely distributed families of epoxide hydrolases (EHs). EHs can transform epoxides to compounds with decreased chemical reactivity, increased water solubility, and altered biological activity.7,8 In addition to participating in the catabolism of JH in insects, mEHs also play important roles in cytoprotection, steroid metabolism, bile acid transport, and xenobiotic metabolism.9 To date, the only structure of the mEH from the fungus Aspergillus niger (termed AnEH, PDB 1QO7) revealed a typical a/b-hydrolase core composed of a twisted eightstranded b-sheet packing on both sides with several a-helices.10,11 Structural analyses suggested a bimolecular nucleophilic substitution (SN2) reaction mechanism involving a standard nucleophile–histidine–acid catalytic triad of Asp–His–Glu/Asp.11 However, the mechanism of substrate recognition and catalysis of mEHs remains unclear. Here we report the crystal structure of Bombyx mori JHEH (BmJHEH) at 2.30 A resolution. Structural analyses together with molecular simulation reveal insights into the specific binding of JH in the active-site pocket. These findings increase our understanding of the substrate recognition and catalysis of mEHs and might help the design of JH-derived pesticides.