Distinctive structural and kinetic properties of an unusual juvenile hormone-hydrolyzing esterase

The insect juvenile hormone specific esterases (JHEs), related to acetylcho linesterases but exhibiting substrate specificity for juvenile hormone (JH) , are essential enzymes for normal insect development, making them attracti ve targets for biorationally designed, environmentally safe pesticides. Ne examine here a new enzyme, JHER, related to, but yet structurally, biochemi cally, and kinetically distinct from, the classical JHE. Both classical JHE and baculovirus-expressed JHER hydrolyze JH show disproportionately higher catalytic rates at higher substrate concentrations (in contrast to substra te inhibition reported for acetylcholinesterase) and are similarly inhibite d by an organophosphate. However, JHER, which possesses an unusual cysteine residue at + 1 to the catalytic serine, is less sensitive to trifluorometh yl ketone transition state analogs designed around the structure of JET. We propose a model in which JHER is expressed just prior to metamorphosis for hydrolysis of a JH-like substrate with hydrophobic backbone, a proximal es ter, and a terminal expoxide or related substitution. (C) 2000 Academic Pre ss.