近日,来自威斯康星大学等处的研究者发现了昆虫体内的一种酶的关键结构组分扮演着多重的角色,包括在表皮和褪黑激素合成以及生物胺脱毒的作用。而且这种酶在埃及伊蚊处于激活状态,埃及伊蚊是众所周知的可以传染黄热病以及登革热的传播者。
这项研究成果刊登在了近日的国际杂志PNAS上。
研究者Jianyong Li和其同事研究了这种酶-芳(香)烷胺N-乙酰基转移酶(aaNAT)。研究小组使用生物信息学技术将昆虫中类似于aaNAT的序列分为了三簇,后期使用晶体学技术,他们观察到了三簇酶类的晶体学结构,最后从两簇酶中发现了蛋白质的生化活性部分。
值得注意的是,研究小组发现了一簇酶类在蚊子中是独一无二的,因此通过对埃及伊蚊进行研究,在其它蚊子如冈比亚按蚊中夜还会有类似的aaNAT酶类。
下一步研究者会进一步研究蚊子体内这种特殊酶类的生理学功能,总之,研究者的发现为开发蚊子体内特异性酶类的生化功能提供基础,以及为后期开发出潜在的杀蚊剂提供思路和指导。(生物谷Bioon.com)
编译自:Enzyme characterization brings biochemists closer to mosquito drug targets
doi:10.1073/pnas.1206828109
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PMID:
Evolution of insect arylalkylamine N-acetyltransferases: Structural evidence from the yellow fever mosquito, Aedes aegypti.
Han Q, Robinson H, Ding H, Christensen BM, Li J.
Arylalkylamine N-acetyltransferase (aaNAT) catalyzes the transacetylation 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, aaNAT5b 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.