近日,，來自威斯康星大學(xué)等處的研究者發(fā)現(xiàn)了昆蟲體內(nèi)的一種酶的關(guān)鍵結(jié)構(gòu)組分扮演著多重的角色,，包括在表皮和褪黑激素合成以及生物胺脫毒的作用,。而且這種酶在埃及伊蚊處于激活狀態(tài)，埃及伊蚊是眾所周知的可以傳染黃熱病以及登革熱的傳播者,。
這項研究成果刊登在了近日的國際雜志PNAS上,。
研究者Jianyong Li和其同事研究了這種酶-芳(香)烷胺N-乙酰基轉(zhuǎn)移酶（aaNAT）,。研究小組使用生物信息學(xué)技術(shù)將昆蟲中類似于aaNAT的序列分為了三簇,，后期使用晶體學(xué)技術(shù)，他們觀察到了三簇酶類的晶體學(xué)結(jié)構(gòu),，最后從兩簇酶中發(fā)現(xiàn)了蛋白質(zhì)的生化活性部分,。
值得注意的是，研究小組發(fā)現(xiàn)了一簇酶類在蚊子中是獨一無二的,，因此通過對埃及伊蚊進(jìn)行研究,，在其它蚊子如岡比亞按蚊中夜還會有類似的aaNAT酶類。
下一步研究者會進(jìn)一步研究蚊子體內(nèi)這種特殊酶類的生理學(xué)功能,，總之,，研究者的發(fā)現(xiàn)為開發(fā)蚊子體內(nèi)特異性酶類的生化功能提供基礎(chǔ)，以及為后期開發(fā)出潛在的殺蚊劑提供思路和指導(dǎo),。（生物谷Bioon.com）
編譯自：Enzyme characterization brings biochemists closer to mosquito drug targets
doi:10.1073/pnas.1206828109
PMC:
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.
