The Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel; Fritz Haber Center for Molecular Dynamics, The Hebrew University, Jerusalem, Israel.
The Institute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel; Fritz Haber Center for Molecular Dynamics, The Hebrew University, Jerusalem, Israel.
Food Chem. 2022 Mar 30;373(Pt A):131393. doi: 10.1016/j.foodchem.2021.131393. Epub 2021 Oct 13.
Naturally occurring sugars usually have d-chirality. While a change in chirality typically affects ligand-receptor interaction, non-caloric l-glucose was reported as sweet for humans. Here we show that l- and d-glucose have similar sensory detection thresholds (0.041 ± 0.006 M for d-glucose, and 0.032 ± 0.007 M for l-glucose) and similar sweetness intensities at suprathreshold concentrations. We demonstrate that l-glucose acts via the sweet taste receptor TAS1R2/TAS1R3, eliciting a dose-dependent activation in cell-based functional assays. Computational docking of glucose to the VFT domain of TAS1R2 suggests two sub-pockets, each compatible with each of the enantiomers. While some polar residues (Y103, D142, N143, S144, Y215) are unique for sub-pocket A and others (D307, T326, E382, R383) for sub-pocket B, no interaction is unique for only one enantiomer. The many options for creating hydrogen bonds with the hydroxyl moieties of glucose explain how both enantiomers can fit each one of the sub-pockets.
天然存在的糖通常具有 d-手性。虽然手性的改变通常会影响配体-受体相互作用，但非热量 l-葡萄糖被报道对人类是甜的。在这里，我们表明 l-和 d-葡萄糖具有相似的感觉检测阈值（d-葡萄糖为 0.041 ± 0.006 M，l-葡萄糖为 0.032 ± 0.007 M），并且在超阈值浓度下具有相似的甜度强度。我们证明 l-葡萄糖通过甜味受体 TAS1R2/TAS1R3 起作用，在基于细胞的功能测定中引发剂量依赖性激活。葡萄糖对 TAS1R2 的 VFT 结构域的计算对接表明存在两个亚口袋，每个亚口袋都与两种对映异构体兼容。虽然一些极性残基（Y103、D142、N143、S144、Y215）是亚口袋 A 的独特残基，而另一些（D307、T326、E382、R383）是亚口袋 B 的独特残基，但没有一个相互作用是仅与一种对映异构体独特的。与葡萄糖的羟基形成氢键的多种选择解释了两种对映异构体如何适合每个亚口袋。
