Structures and functions of insect arylalkylamine N-acetyltransferase (iaaNAT); a key enzyme for physiological and behavioral switch in arthropods.

Structures and functions of insect arylalkylamine N-acetyltransferase (iaaNAT); a key enzyme for physiological and behavioral switch in arthropods.
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昆虫芳基烷基胺N-乙酰转移酶(Iaanat)的结构和功能;节肢动物中生理和行为转换的关键酶。

DOI:
10.3389/fphys.2015.00113
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发表时间:
2015
影响因子:
4
通讯作者:
Takeda M
Takeda M
中科院分区:
医学2区
文献类型:
--
作者:
Hiragaki S;Suzuki T;Mohamed AA;Takeda M

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N-乙酰转移酶(NAT)的进化似乎很复杂。脊椎动物芳基烷基胺N-乙酰基转移酶(aaNAT)已被广泛研究,因为它导致褪黑激素的合成,褪黑激素是感光细胞中普遍存在的多功能神经激素,并被称为夜晚的化学标志。褪黑激素还充当活性氧的清除剂。无脊椎动物也是如此。因此,NAT在昼夜节律功能中具有不同的功能含义,如时间酶(aaNAT)和异生物质反应(芳胺NAT或简称NAT)。NAT属于一个更广泛的酶组,GCN 5相关的N-乙酰转移酶超家族。由于低序列同源性和看似快速的结构分化,NAT的命名可能会令人困惑。然而,生物信息学的出现有助于对这类酶进行分类;脊椎动物有两个不同的亚类,时间酶类型和异生素类型,异生素类型具有更广泛的底物范围,包括咪唑胺,药理学药物,环境毒物甚至组蛋白。昆虫aaNAT(iaaNAT)在进化史上形成了自己的分支,与脊椎动物aaNAT不同。节肢动物是独特的,因为该门具有外骨骼,其中来自N-乙酰化单胺的醌类在甲壳素和节肢动物素的偶联中起作用。单胺氧化酶(MAO)活性在昆虫中是有限的,但NAT介导的降解占主导地位。然而,意想不到的iaaNAT不仅发生在节肢动物中,而且也发生在基部后口动物中,因此更无定形。我们的分析表明,iaaNATs具有独特的生理作用,但在同一时间,它发挥了作用的时间酶功能,至少在光周期。光周期被认为是昼夜节律系统的一个功能,但详细的分子机制还没有很好的理解。我们提出了一个分子假说,光周期在柞蚕的NAT的转录调控的基础上联锁的昼夜节律系统。因此,该酶在昆虫中既具有独特的作用,又具有普遍的作用。iaaNAT在生理调节中的独特作用促使该系统用于害虫综合治理(IPM)。我们确实展示了一个用重组酶筛选化合物的成功例子,进一步的尝试似乎很有希望。
The evolution of N-acetyltransfeases (NATs) seems complex. Vertebrate arylalkylamine N-acetyltransferase (aaNAT) has been extensively studied since it leads to the synthesis of melatonin, a multifunctional neurohormone prevalent in photoreceptor cells, and is known as a chemical token of the night. Melatonin also serves as a scavenger for reactive oxygen species. This is also true with invertebrates. NAT therefore has distinct functional implications in circadian function, as timezymes (aaNAT), and also xenobiotic reactions (arylamine NAT or simply NAT). NATs belong to a broader enzyme group, the GCN5-related N-acetyltransferase superfamily. Due to low sequence homology and a seemingly fast rate of structural differentiation, the nomenclature for NATs can be confusing. The advent of bioinformatics, however, has helped to classify this group of enzymes; vertebrates have two distinct subgroups, the timezyme type and the xenobiotic type, which has a wider substrate range including imidazolamine, pharmacological drugs, environmental toxicants and even histone. Insect aaNAT (iaaNAT) form their own clade in the phylogeny, distinct from vertebrate aaNATs. Arthropods are unique, since the phylum has exoskeleton in which quinones derived from N-acetylated monoamines function in coupling chitin and arthropodins. Monoamine oxidase (MAO) activity is limited in insects, but NAT-mediated degradation prevails. However, unexpectedly iaaNAT occurs not only among arthropods but also among basal deuterostomia, and is therefore more apomorphic. Our analyses illustrate that iaaNATs has unique physiological roles but at the same time it plays a role in a timezyme function, at least in photoperiodism. Photoperiodism has been considered as a function of circadian system but the detailed molecular mechanism is not well understood. We propose a molecular hypothesis for photoperiodism in Antheraea pernyi based on the transcription regulation of NAT interlocked by the circadian system. Therefore, the enzyme plays both unique and universal roles in insects. The unique role of iaaNATs in physiological regulation urges the targeting of this system for integrated pest management (IPM). We indeed showed a successful example of chemical compound screening with reconstituted enzyme and further attempts seem promising.
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