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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Evolution of insect arylalkylamine N-acetyltransferases:Structural evidence from the yellow fever mosquito,Aedes aegypti
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Evolution of insect arylalkylamine N-acetyltransferases:Structural evidence from the yellow fever mosquito,Aedes aegypti

机译：昆虫芳基烷基胺N-乙酰基转移酶的进化：黄热蚊，埃及伊蚊的结构证据

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摘要

Arylalkylamine N-acetyltransferase (aaNAT) catalyzes the transace-tylation from acetyl-CoA to arylalkylamines. aaNATs are involved in sclerotization and neurotransmitter inactivation in insects. Phyletic distribution analysis confirms three clusters of aaNAT-like sequences in insects: typical insect aaNAT, polyamine NAT-like aaNAT, and mosquito unique putative aaNAT (paaNAT). Here we studied three proteins: aaNAT2, aaNAT5b, and paaNAT7, each from a different cluster. aaNAT2, a protein from the typical insect aaNAT cluster, uses histamine as a substrate as well as the previously identified arylalkylamines. aaNAT5b, a protein from polyamine NAT -like aaNAT cluster, uses hydrazine and histamine as substrates. The crystal structure of aaNAT2 was determined using single-wavelength anomalous dispersion methods, and that of native aaNAT2, aaNATSb and paaNAT7 was detected using molecular replacement techniques. All three aaNAT structures have a common fold core of GCN5-related N-acetyltransferase superfamily proteins, along with a unique structural feature: helix/helices between β3 and β4 strands. Our data provide a start toward a more comprehensive understanding of the structure-function relationship and physiology of aaNATs from the mosquito Aedes aegypti and serve as a reference for studying the aaNAT family of proteins from other insect species. The structures of three different types of aaNATs may provide targets for designing insecticides for use in mosquito control.
机译：芳基烷基胺N-乙酰基转移酶（aaNAT）催化从乙酰基CoA到芳基烷基胺的酯基转移反应。 aaNATs参与昆虫的硬化和神经递质失活。系统分布分析证实了昆虫中的三个类似于aaNAT的序列簇：典型的昆虫aaNAT，类似多胺NAT的aaNAT和蚊子独特的假定aaNAT（paaNAT）。在这里，我们研究了三种蛋白质：aaNAT2，aaNAT5b和paaNAT7，它们分别来自不同的簇。 aaNAT2是典型昆虫aaNAT簇中的一种蛋白质，它使用组胺作为底物以及先前鉴定的芳基烷基胺。 aaNAT5b是一种类似多胺NAT的aaNAT簇的蛋白质，它使用肼和组胺作为底物。使用单波长异常色散方法确定aaNAT2的晶体结构，并使用分子置换技术检测天然aaNAT2，aaNATSb和paaNAT7的晶体结构。所有三个aaNAT结构都具有GCN5相关的N-乙酰基转移酶超家族蛋白的共同折叠核心，并具有独特的结构特征：β3和β4链之间的螺旋/螺旋。我们的数据为更全面地了解埃及伊蚊（Aedes aegypti）的aaNATs的结构-功能关系和生理学提供了一个起点，并为研究其他昆虫物种的aaNAT家族蛋白提供了参考。三种不同类型的aaNAT的结构可为设计用于灭蚊的杀虫剂提供目标。

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