Promiscuity and selectivity of bitter molecules and their receptors
Promiscuity and selectivity of bitter molecules and their receptors
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DOI：
10.1016/j.bmc.2015.04.025
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发表时间：
2015-07-15
影响因子：
3.5
通讯作者：
Niv, Masha Y.
中科院分区：
文献类型：
--
作者：
Di Pizio, Antonella;Niv, Masha Y.
苦味对生存至关重要，因为它可以防止摄入有毒化合物，这些化合物通常是苦的。苦味感知由苦味受体（TAS 2 R）介导，苦味受体是G蛋白偶联受体（GPCR）的一个亚家族。TAS 2 R亚型的数量是物种依赖性的，从鸡的3种到青蛙的50种不等。TAS 2 R为研究滥交提供了一个有趣的案例：一些受体仍然是孤儿，或者几乎没有已知的激动剂，而另一些受体可以被许多结构不同的化合物激活。这些配体在它们激活的TAS 2 R库中也是不同的：一些苦味化合物对单个TAS 2 R具有选择性，而另一些则激活多个TAS 2 R。通过化学信息学方法探索苦味受体及其化合物的选择性/混杂性。TAS 2 R-混杂和TAS 2 R-选择性苦味分子被发现在化学特征上不同，例如AlogP、E-状态、总电荷、环数、球形度和重原子数。这允许预测苦味配体对TAS 2 R的选择性。有趣的是，尽管混杂的TAS 2 R被TAS 2 R-混杂的和TAS 2 R-选择性的化合物激活，但人体中几乎所有的选择性TAS 2 R都被混杂的化合物激活，这些化合物无论如何都被其他TAS 2 R识别。因此，独特的配体，这可能是发展选择性TAS 2 R的进化驱动力，仍然需要解开。(C)2015爱思唯尔有限公司版权所有。
Bitter taste is essential for survival, as it protects against consuming poisonous compounds, which are often bitter. Bitter taste perception is mediated by bitter taste receptors (TAS2Rs), a subfamily of G-protein coupled receptors (GPCRs). The number of TAS2R subtypes is species-dependent, and varies from 3 in chicken to 50 in frog. TAS2Rs present an intriguing case for studying promiscuity: some of the receptors are still orphan, or have few known agonists, while others can be activated by numerous, structurally dissimilar compounds. The ligands also vary in the repertoire of TAS2Rs that they activate: some bitter compounds are selective toward a single TAS2R, while others activate multiple TAS2Rs. Selectivity/promiscuity profile of bitter taste receptors and their compounds was explored by a chemoinformatic approach. TAS2R-promiscuous and TAS2R-selective bitter molecules were found to differ in chemical features, such as AlogP, E-state, total charge, number of rings, globularity, and heavy atom count. This allowed the prediction of bitter ligand selectivity toward TAS2Rs. Interestingly, while promiscuous TAS2Rs are activated by both TAS2R-promiscuous and TAS2R-selective compounds, almost all selective TAS2Rs in human are activated by promiscuous compounds, which are recognized by other TAS2Rs anyway. Thus, unique ligands, that may have been the evolutionary driving force for development of selective TAS2Rs, still need to be unraveled. (C) 2015 Elsevier Ltd. All rights reserved.