Juvenile hormone JH is an insect hormone containing an alpha,beta-unsaturated ester consisting of a small alcohol and long hydrophobic acid. JH degradation is required for proper insect development. One pathway of this degradation is through juvenile hormone esterase JHE which cleaves the JH ester bond to produce methanol and JH acid. Another way of degradation of JH is epoxyde hydrolysis. Most insect species contain only juvenile hormone (JH) III. To date JH 0, JH I, and JH II have been identified only in the Lepidoptera (butterflies and moths). The form JHB3 (JH III bisepoxide) appears to be the most important JH in the Diptera, or flies. Certain species of crustaceans have been shown to produce and secrete methyl farnesoate, which is juvenile hormone III lacking the epoxide group. Methyl farnesoate is believed to play a role similar to that of JH in crustaceans. In drosophila DmJHE is the hormone esterase with precise regulation and highly specific activity for its substrate, juvenile hormone. DmJHEdup is an odorant degrading esterase (ODE) responsible for processing various kairomones in antennae
The Drosophila melanogaster enzymes juvenile hormone esterase (DmJHE) and its duplicate, DmJHEdup, present ideal examples for studying the structural changes involved in the neofunctionalization of enzyme duplicates. DmJHE is a hormone esterase with precise regulation and highly specific activity for its substrate, juvenile hormone. DmJHEdup is an odorant degrading esterase (ODE) responsible for processing various kairomones in antennae. Our phylogenetic analysis shows that the JHE lineage predates the hemi/holometabolan split and that several duplications of JHEs have been templates for the evolution of secreted beta-esterases such as ODEs through the course of insect evolution. Our biochemical comparisons further show that DmJHE has sufficient substrate promiscuity and activity against odorant esters for a duplicate to evolve a general ODE function against a range of mid-long chain food esters, as is shown in DmJHEdup. This substrate range complements that of the only other general ODE known in this species, Esterase 6. Homology models of DmJHE and DmJHEdup enabled comparisons between each enzyme and the known structures of a lepidopteran JHE and Esterase 6. Both JHEs showed very similar active sites despite low sequence identity (30%). Both ODEs differed drastically from the JHEs and each other, explaining their complementary substrate ranges. A small number of amino acid changes are identified that may have been involved in the early stages of the neofunctionalization of DmJHEdup. Our results provide key insights into the process of neofunctionalization and the structural changes that can be involved.
Title: Juvenile hormone esterase: biochemistry and structure Kamita SG, Hammock BD Ref: Journal of Pesticide Science, 35:265, 2010 : PubMed
Normal insect development requires a precisely timed, precipitous drop in hemolymph juvenile hormone (JH) titer. This drop occurs through a coordinated halt in JH biosynthesis and increase in JH metabolism. In many species, JH esterase (JHE) is critical for metabolism of the resonance-stabilized methyl ester of JH. JHE metabolizes JH with a high kcat/KM ratio that results primarily from an exceptionally low KM. Here we review the biochemistry and structure of authentic and recombinant JHEs from six insect orders, and present updated diagnostic criteria that help to distinguish JHEs from other carboxylesterases. The use of a JHE-encoding gene to improve the insecticidal efficacy of biopesticides is also discussed.
Juvenile hormone (JH) is an insect hormone containing an alpha,beta-unsaturated ester consisting of a small alcohol and long, hydrophobic acid. JH degradation is required for proper insect development. One pathway of this degradation is through juvenile hormone esterase (JHE), which cleaves the JH ester bond to produce methanol and JH acid. JHE is a member of the functionally divergent alpha/beta-hydrolase family of enzymes and is a highly efficient enzyme that cleaves JH at very low in vivo concentrations. We present here a 2.7 A crystal structure of JHE from the tobacco hornworm Manduca sexta (MsJHE) in complex with the transition state analogue inhibitor 3-octylthio-1,1,1-trifluoropropan-2-one (OTFP) covalently bound to the active site. This crystal structure, the first JHE structure reported, contains a long, hydrophobic binding pocket with the solvent-inaccessible catalytic triad located at the end. The structure explains many of the interactions observed between JHE and its substrates and inhibitors, such as the preference for small alcohol groups and long hydrophobic backbones. The most potent JHE inhibitors identified to date contain a trifluoromethyl ketone (TFK) moiety and have a sulfur atom beta to the ketone. In this study, sulfur-aromatic interactions were observed between the sulfur atom of OTFP and a conserved aromatic residue in the crystal structure. Mutational analysis supported the hypothesis that these interactions contribute to the potency of sulfur-containing TFK inhibitors. Together, these results clarify the binding mechanism of JHE inhibitors and provide useful observations for the development of additional enzyme inhibitors for a variety of enzymes.
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No structure scheme yet for this family
Structures in Juvenile_hormone_esterase family (1)
