4.5 Article

Arylalkalamine N-acetyltransferase-1 acts on a secondary amine in the yellow fever mosquito, Aedes aegypti

Journal

FEBS LETTERS
Volume 596, Issue 8, Pages 1081-1091

Publisher

WILEY
DOI: 10.1002/1873-3468.14316

Keywords

epinephrine; functional analysis; haemostasis; mosquito; N-acetyltransferase; novel substrate

Funding

  1. National Natural Science Foundation of China [31860702]
  2. Hainan Provincial Major RD Program [ZDKJ2021035]

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This study reports a new biochemical function of aaNAT1 in metabolizing epinephrine, revealing its potential impact on mosquitoes.
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.

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