Chen C Y-C, Chen Y-F, Tsai H-Y
Dept. of Biological Science and Technology, China Medical University, Taichung, 40402 Taiwan, ROC.
J Biomol Struct Dyn. 2008 Aug;26(1):57-64. doi: 10.1080/07391102.2008.10507223.
The reliable structure of gamma aminobutyric acid type A (GABA-A) receptor was built based on several criteria. According to zolpidem and GABA binding conformations, the key residues that were indicated to be the determination of binding were consistent with our simulation. Investigation of the major effective constituents from suanzaoren to modulate the GABA-A was the aim of the study. Jujuboside A, which was indicated to be the effective constituent from suanzaoren, had no blood-brain barrier (BBB) penetration and was unable to bind at both binding sites due to its large volume. In addition, the glycoside groups on jujuboside A were easily to be hydrolyzed. In contrast, jujubogenin, which was hydrolyzed from jujuboside A, had the most compatible binding conformation. In addition, jujubogenin formed two HBs with the key residue beta(2)-Thr226 and beta(2)-Tyr229 at the GABA binding site. Moreover, it gained the comparably highest scoring values among suanzaoren constituents. Furthermore, the Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) descriptor predicted that jujubogenin have good BBB penetration. Consequently, we suggested jujubogenin to be the effective suanzaoren constituent to mediate the GABA-A receptor.
基于多项标准构建了可靠的A型γ-氨基丁酸（GABA-A）受体结构。根据唑吡坦和GABA的结合构象，表明决定结合的关键残基与我们的模拟结果一致。研究酸枣仁中调节GABA-A的主要有效成分是本研究的目的。酸枣仁皂苷A被认为是酸枣仁的有效成分，它没有血脑屏障（BBB）通透性，并且由于其体积较大而无法在两个结合位点结合。此外，酸枣仁皂苷A上的糖苷基团容易水解。相比之下，从酸枣仁皂苷A水解得到的酸枣仁皂苷元具有最匹配的结合构象。此外，酸枣仁皂苷元在GABA结合位点与关键残基β(2)-Thr226和β(2)-Tyr229形成了两个氢键。而且，它在酸枣仁成分中获得了相对最高的评分值。此外，吸收、分布、代谢、排泄和毒性（ADMET）描述符预测酸枣仁皂苷元具有良好的血脑屏障通透性。因此，我们认为酸枣仁皂苷元是介导GABA-A受体的有效酸枣仁成分。
