Hasan Md Nazmul, Hosen Mohammad Jakir, Thakur Prasoon Kumar, Abir Ruhshan Ahmed, Zubaer Abdullah, Renkai Guo, Yoshida Mayumi, Ohta Hiroto, Lee Jae Man, Kusakabe Takahiro, Hirashima Akinori
Laboratory of Pesticide Chemistry, Division of Molecular Biosciences, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan; Department of Genetic Engineering and Biotechnology, Jessore University of Science and Technology, Jessore, Bangladesh.
Department of Genetic Engineering and Biotechnology, Shahjalal University of Science and Technology, Sylhet, Bangladesh.
Int J Biol Macromol. 2016 Dec;93(Pt A):889-895. doi: 10.1016/j.ijbiomac.2016.06.026. Epub 2016 Jun 26.
Biogenic amines are common biologically active substances extended within the whole animal kingdom where they play vital roles as signal transducer as well as regulator of cell functions. One of these biogenic amines called octopamine (OA) is synthesized from tyramine (TA) by the catalysis of tyramine-β-hydroxylase (TβH) originated in the insect nervous system. Both TA and OA act as neurotransmitters, neurohormones and neuromodulators in the arthropod nervous system. Herein, the inhibitory activity of 1-arylimidazole-2(3H)-thiones (AITs) was tested on cloned Drosophila tyramine-β-hydroxylase (DmTβH) expressed in Bombyx mori strain. Radiolabelled H-TA was used to analyze the activity of AITs exhibited inhibitory effects on DmTβH, whose ID values range from 0.02 to 2511nM where DmTβH was inhibited in a dose-dependent manner at pH 7.6 and 25°C during a 30min of incubation. To understand the catalytic role of the TβH, a three dimensional structure of the TβH from Drosophila melanogaster was constructed by homology modeling using the Phyre2 web server with 100% confidence. The modeled three-dimensional structure of TβH was used to perform the docking study with AITs. This may give more insights to precise design of inhibitors for TβH to control insect's population.
生物胺是广泛存在于整个动物界的常见生物活性物质，它们作为信号转导分子以及细胞功能调节剂发挥着至关重要的作用。其中一种生物胺名为章鱼胺（OA），它由酪胺（TA）在昆虫神经系统中起源的酪胺-β-羟化酶（TβH）催化下合成。TA和OA在节肢动物神经系统中均充当神经递质、神经激素和神经调质。在此，测试了1-芳基咪唑-2(3H)-硫酮（AITs）对在家蚕品系中表达的克隆果蝇酪胺-β-羟化酶（DmTβH）的抑制活性。使用放射性标记的H-TA来分析AITs对DmTβH的活性，其ID值范围为0.02至2511nM，在pH 7.6和25°C孵育30分钟期间，DmTβH以剂量依赖性方式受到抑制。为了解TβH的催化作用，使用Phyre2网络服务器通过同源建模以100%的置信度构建了黑腹果蝇TβH的三维结构。TβH的模拟三维结构用于与AITs进行对接研究。这可能为精确设计TβH抑制剂以控制昆虫种群提供更多见解。
