Arylalkalamine N‐acetyltransferase‐1 acts on a secondary amine in the yellow fever mosquito, Aedes aegypti. Issue 8 (23rd February 2022)

• Record Type: Journal Article
• Authors: Zhang, Lei; Tang, Yu; Chen, Huaqing; Zhu, Xiaojing; Gong, Xue; Wang, Shouchuang; Luo, Jie; Han, Qian
• Is Part Of: FEBS letters. Volume 596:Issue 8(2022)
• Page Start: 1081
• Page End: 1091
• Publication Date: 2022-02-23
• Subjects: epinephrine -- functional analysis -- haemostasis -- mosquito -- N‐acetyltransferase -- novel substrate; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14316
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Arylalkylamine N ‐acetyltransferase (aaNAT) in Aedes aegypti is primarily involved in cuticle pigmentation and formation. The reported arylalkylamine substrates are all primary amines. In this study, we report a novel substrate, a secondary amine, of Ae . aegypti aaNAT1. The recombinant aaNAT1 protein exhibited high activity to a secondary amine, epinephrine, which has not been reported for any aaNATs previously. Structure–activity relationship study demonstrated that aaNAT1 has an epinephrine‐binding site, and molecular docking and dynamic simulation showed that epinephrine is quite stable in the active cavity. Further functional studies demonstrated that epinephrine affected mosquito fecundity, egg hatching and development. The new biochemical function of aaNAT1 in metabolizing epinephrine could reduce some negative effects of the compound in the mosquito. Abstract : The substrates of arylalkylamine N ‐acetyltransferase (aaNAT) are usually primary amines. Herein, we report that mosquito aaNAT1 acts on a secondary amine, epinephrine, efficiently. A functional analysis demonstrated that epinephrine affects mosquito fecundity, egg hatching and development, and aaNAT1 mutant mosquitos had lower anti‐hemostatic ability than wild type mosquitos. These findings suggest that aaNAT1 has a role in anti‐hemostasis via metabolizing epinephrine.