Reference - Detail
|Author||Tsugehara T, Imai T, Takeda M.|
|Title||Characterization of arylalkylamine N-acetyltransferase from silkmoth (Antheraea pernyi) and pesticidal drug design based on the baculovirus-expressed enzyme.|
|Journal||Comp Biochem Physiol C Toxicol Pharmacol|
Arylalkylamine N-acetyltransferase (AANAT; EC 220.127.116.11) catalyzes the N-acetylation of arylalkylamines. A cDNA encoding AANAT (ApAANAT) was cloned from Antheraea pernyi by PCR. The cDNA of 1966 bp encodes a 261 amino acid protein. The amino acid sequence was found to have a high homology with Bombyx mori AANAT (BmNAT) but had very low homology with vertebrate AANATs. Amino acid sequence analysis revealed that four insect AANATs cloned from three species including ApAANAT formed a distinct cluster from the vertebrate group. A recombinant ApAANAT protein was expressed in Sf9 cells using a baculovirus expression system, having AANAT activity. The transformed cell extract acetylated tryptamine, serotonin, dopamine, tyramine, octopamine and norepinephrine. The AANAT activity was inhibited at over 0.03 mM tryptamine. Although insect AANATs have been considered as a target of insecticide, this type of insecticide has never been developed. Screening a chemical library of Otsuka Chemical Co., Ltd., we found a novel compound and its derivatives that inhibited the AANAT activity of ApAANAT. This may facilitate investigation of the monoamine metabolic pathway in insects and the development of new types of insecticides and inhibitors of AANATs.
|MeSH||Acetylation Amino Acid Sequence Animals Arylalkylamine N-Acetyltransferase / classification Arylalkylamine N-Acetyltransferase / genetics Arylalkylamine N-Acetyltransferase / metabolism* Baculoviridae / genetics Base Sequence Biocatalysis / drug effects Biogenic Monoamines / metabolism Blotting, Western DNA, Complementary / genetics Drug Design* Enzyme Inhibitors / metabolism Enzyme Inhibitors / pharmacology Genetic Vectors / genetics Insect Proteins / antagonists & inhibitors Insect Proteins / genetics Insect Proteins / metabolism* Kinetics Molecular Sequence Data Moths / enzymology* Moths / genetics Pesticides / chemistry Pesticides / pharmacology Phylogeny Sequence Homology, Amino Acid Sf9 Cells Substrate Specificity Tryptamines / metabolism Tryptamines / pharmacology|
|WOS Category||ZOOLOGY TOXICOLOGY ENDOCRINOLOGY & METABOLISM BIOCHEMISTRY & MOLECULAR BIOLOGY|