Distinctive structural and kinetic properties of an unusual juvenile hormone-hydrolyzing esterase.
The insect juvenile hormone specific esterases (JHEs), related to acetylcholinesterases but exhibiting substrate specificity for juvenile hormone (JH), are essential enzymes for normal insect development, making them attractive targets for biorationally designed, environmentally safe pesticides. We examine here a new enzyme, JHER, related to, but yet structurally, biochemically, 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 substrate inhibition reported for acetylcholinesterase) and are similarly inhibited by an organophosphate. However, JHER, which possesses an unusual cysteine residue at +1 to the catalytic serine, is less sensitive to trifluoromethyl ketone transition state analogs designed around the structure of JH. 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 ester, and a terminal expoxide or related substitution.
Kadono-Okuda
K
K
Graduate Center for Toxicology, University of Kentucky, Lexington 40506-0054, USA.
Ridley
B
B
Jones
D
D
Jones
G
G
D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020134:Catalytic Domain / Q000235:genetics; D002460:Cell Line; D019476:Insect Proteins; D007605:Juvenile Hormones / Q000378:metabolism*; D007700:Kinetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry; D018411:Spodoptera; D013379:Substrate Specificity
D019476:Insect Proteins; D007605:Juvenile Hormones; D011994:Recombinant Proteins; D012694:Serine; D002265:Carboxylic Ester Hydrolases; C089555:JHER protein, Trichoplusia ni