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用于阿尔茨海默病和 2 型糖尿病的 AChE 和 BChE 的药用化合物的功能分析和分子对接研究。

Functional Analysis and Molecular Docking studies of Medicinal Compounds for AChE and BChE in Alzheimer's Disease and Type 2 Diabetes Mellitus.

机构信息

Department of Biochemistry/Bioinformatics, GIS, GITAM University, Visakhapatnam-530045, AP, India.

出版信息

Aging Dis. 2013 Jun 20;4(4):186-200. Print 2013 Aug.

Abstract

Acetylcholinesterase and Butyrylcholinesterase share unravelling link with components of metabolic syndromes that's characterised by low levels of HDL cholesterol, obesity, high fast aldohexose levels, hyper-trigliceridaemia and high blood pressure, by regulation of cholinergic transmission and therefore the enzyme activity within a living system. The phosphomotifs associated with amino acid and tyrosine binding motifs in AChE and BChE were known to be common. Phylogenetic tree was constructed to these proteins usinf UPGMA and Maximum Likelihood methods in MEGA software has shown interaction of AChE and BChE with ageing diseases like Alzheimer's disease and Diabetes. AChE has shown closely related to BChE, retinol dehydrogenase and β-polypeptide. The present studies is also accomplished that AChE, BChE, COLQ, HAND1, APP, NLGN2 and NGF proteins has interactions with diseases such as Alzheimer's and D2M using Pathwaylinker and STRING. Medicinal compounds like Ortho-7, Dibucaine and HI-6 are predicted as good targets for modeled AChE and BChE proteins based on docking studies. Hence perceptive studies of cholinesterase structure and the biological mechanisms of inhibition are necessary for effective drug development.

摘要

乙酰胆碱酯酶和丁酰胆碱酯酶与代谢综合征的组成部分有着尚未解开的联系,这些组成部分的特征是高密度脂蛋白胆固醇水平低、肥胖、高果糖水平、高甘油三酯血症和高血压,通过调节胆碱能传递,从而调节活系统中的酶活性。已知与 AChE 和 BChE 中的氨基酸和酪氨酸结合基序相关的磷酸基序是常见的。使用 MEGA 软件中的 UPGMA 和最大似然法构建了这些蛋白质的系统发育树,结果表明 AChE 和 BChE 与阿尔茨海默病和糖尿病等衰老疾病相互作用。AChE 与 BChE、视黄醇脱氢酶和β-多肽密切相关。目前的研究还表明,AChE、BChE、COLQ、HAND1、APP、NLGN2 和 NGF 蛋白与阿尔茨海默病和 D2M 等疾病存在相互作用,使用 Pathwaylinker 和 STRING 进行了研究。基于对接研究,预测 Ortho-7、二丁卡因和 HI-6 等药物化合物是 AChE 和 BChE 蛋白的良好靶标。因此,对胆碱酯酶结构和抑制的生物学机制进行感知研究对于有效的药物开发是必要的。

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