Han ethnicity-specific type 2 diabetic treatment from traditional Chinese medicine?
Han ethnicity-specific type 2 diabetic treatment from traditional Chinese medicine?
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DOI：
10.1080/07391102.2012.732340
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发表时间：
2013-11-01
影响因子：
4.4
通讯作者：
Chen, Calvin Yu-Chian
中科院分区：
文献类型：
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作者：
Chen, Kuan-Chung;Chang, Su-Sen;Chen, Calvin Yu-Chian
胰岛素降解酶(IDE)基因是中国汉族人群特有的2型糖尿病易感基因之一。IDE是一种锌金属内肽酶，是控制胰岛素降解的潜在靶点。通过对中药的吸收、分布、代谢、排泄和毒性等药代动力学性质的虚拟筛选和评价，从中药中筛选出潜在的抑制IDE的先导化合物。通过分子动力学(MD)模拟验证了分子对接模拟得到的络合物的稳定性。排在前三位的中草药化合物二氢咖啡酸、异丙酚苷IV和东莨菪素与关键残基Asn139形成稳定的氢键相互作用，并通过锌与活性口袋残基His108、His112和Glu189相连。扭转角轨迹也表明每个配体与IDE有稳定的相互作用。分子水平分析表明，候选中药可能通过与活性部位的竞争结合和空间位阻来影响IDE。结构特征分析表明，大量的羟基和羧基有助于将配体锚定在络合物中。因此，我们建议将排名前三位的中药化合物作为针对IDE蛋白的潜在抑制剂来控制2型糖尿病患者的胰岛素降解。http://proteopedia.org/w/Journal:JBSD:29上的Proteopedia中提供了一个动画交互3D补体(I3DC)
Insulin-degrading enzyme (IDE) gene is one of the type 2 diabetes mellitus susceptibility genes specific to the Han Chinese population. IDE, a zinc-metalloendopeptidase, is a potential target for controlling insulin degradation. Potential lead compounds for IDE inhibition were identified from traditional Chinese medicine (TCM) through virtual screening and evaluation of their pharmacokinetic properties of absorption, distribution, metabolism, excretion, and toxicity. Molecular dynamics (MD) simulation was performed to validate the stability of complexes from docking simulation. The top three TCM compounds, dihydrocaffeic acid, isopraeroside IV, and scopolin, formed stable H-bond interactions with key residue Asn139, and were linked to active pocket residues His108, His112, and Glu189 through zinc. Torsion angle trajectories also indicated some stable interactions for each ligand with IDE. Molecular level analysis revealed that the TCM candidates might affect IDE through competitive binding to the active site and steric hindrance. Structural feature analysis reveals that high amounts of hydroxyl groups and carboxylic moieties contribute to anchor the ligand within the complex. Hence, we suggest the top three TCM compounds as potential inhibitor leads against IDE protein to control insulin degradation for type 2 diabetes mellitus.An animated interactive 3D complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:29