Functional Analysis of Amino Acid Residues Responsible for Substrate Specificity of GH13_17 α‑Glucosidase from Aedes aegypti Saliva (AaMalI)

埃及伊蚊唾液中 GH13_17 α-葡萄糖苷酶 (AaMalI) 底物特异性氨基酸残基的功能分析

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Abstract

The α-glucosidase (AaMalI) in Aedes aegypti saliva belongs to glycoside hydrolase family 13, subfamily 17 (GH13_17) and plays a crucial role in the digestion of sucrose, which is the main sugar involved in insect metabolism. The amino-acid residues in the conserved region II have been reported as the key residues for sucrose specificity in GH13_17. Using mutagenesis, this study expressed and purified recombinant AaMalI and determined the molecular mechanism related to substrate specificity. The optimal activity was at pH 6.3 and 40 °C. AaMalI had a trisaccharide specificity similar to GH13 α-glucosidases and preference for sucrose over maltose. The single mutation of Y223H and the double mutation of P222N/Y223H altered the substrate preference from sucrose to maltose. Structural analysis of the AaMalI model obtained by superimposition with the maltose-bound complex suggested that Tyr292 stabilizes the d-glucosyl moiety at subsite +1, whereas His223 indirectly contributes to maltose hydrolysis. These findings provide structural insights into AaMalI substrate specificity and support its potential as a target for vector mosquito control.

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