Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 661, Issue -, Pages 107-116Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2018.11.015
Keywords
AANAT; Bombyx mori; N-acylarylakylamine; Kinetic mechanism; Chemical mechanism
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Funding
- Florida Center for Excellence for Biomolecular and Targeted Therapeutics (FCoE-BITT) [GALS020]
- University of South Florida (a Creative Scholarship Grant from the College of Arts and Sciences)
- Shirley W. and William L. Griffin Foundation
- National Institute of Drug Abuse at the National Institutes of Health [R03-DA034323]
- National Institute of General Medical Science of the National Institutes of Health [R15-GM107864]
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The arylalkylamine N-acyltransferases (AANATs) are enzymes that catalyze the acyl-CoA-dependent formation of N-acylarylalkylamides: acyl-CoA + arylalkylamine -> N-acylarylalkylamides + CoA-SH. Herein, we describe our study of a previously uncharacterized AANAT from Bombyx mori: Bm-iAANAT3. Bm-iAANAT3 catalyzes the direct formation of N-acylarylalkylamides and accepts a broad range of short-chain acyl-CoA thioesters and amines as substrates. Acyl-CoA thioesters possessing an acyl chain length > 10 carbon atoms are not substrates for Bm-iAANAT3. We report that Bm-iAANAT3 is a versatile generalist, most likely, functioning in amine acetylation - a reaction in amine inactivation/excretion, cuticle sclerotization, and melanism. We propose a kinetic and chemical mechanism for Bm-iAANAT3 that is consistent with our steady-state kinetic analysis, deadend inhibition studies, determination of the pH-rate profiles, and site-directed mutagenesis of a catalytically important amino acid in Bm-iAANAT3. These mechanistic studies of Bm-iAANAT3 will foster the development of novel compounds targeted against this enzyme and other insect AANATs for the control of insect pests.
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