解码人类嗅觉受体OR8D1由索托反体激活的潜在分子机制
Juan Wang1,2,3, Danqing Wang1,2, Mingquan Huang1,2
1Key Laboratory of Brewing Molecular Engineering of China Light Industry, Beijing Technology & Business University (BTBU), Beijing 100048, China.
Journal of agricultural and food chemistry
|February 22, 2024
概括
石化化合物索托隆对其R-和S-反体具有独特的气味和检测值. S型是OR8D1受体的更强烈的激动剂,特定的氨基酸残留被认为对这种反选择性至关重要.
科学领域:
- 味道和香味化学 味道和香味化学
- 嗅觉受体研究 嗅觉受体研究
- 分子生物物理学 分子生物物理学
背景情况:
- 索托隆是食品工业中重要的性化合物,以其独特的芳香特征而闻名.
- 了解sotolone的酶选择性感知对于风味和香味应用至关重要.
- 气味受体 (ORs) 在检测挥发性化合物及其立体异构体方面发挥着关键作用.
研究的目的:
- 为了分离和描述 (R) -和 (S) -sotolone的气味概况和检测值.
- 为了研究索托隆反体与嗅觉受体OR8D1.1的相互作用.
- 确定负责OR8D1对索托隆的酶选择性反应的分子决定因素.
主要方法:
- (R) - 和 (S) - 索托的基拉分离.
- 气相色谱-光度计 (GC-O) 用于气味的特征和气味值的确定.
- HEK293基于细胞的发光量测试用于受体响应.
- 分子动力学 (MD) 模拟和分子力学Poisson-Boltzmann表面积 (MM/PBSA) 分析.
- 气味对接,多个序列对齐,部位定向突变发生和功能研究.
主要成果:
- 确定了不同的气味配置和气味值: (R) - 索托隆 (烟雾,烧,草药,绿色; 0.0514μg/m3), (S) - 索托隆 (甜,奶,酸,坚果; 0.0048μg/m3).
- 与 (R) - 索托相比, (S) - 索托作为OR8D1的激动剂具有显著更高的功效 (EC50: 84.98 ± 1.05 μmol/L与167.20 ± 0.25 μmol/L).
- 医学医学模拟表明, (S) - 索托和OR8D1.1之间的复合物更稳定.
- 确定了11种氨基酸残留物对OR8D1对索托的酶选择性至关重要,N2065·46对 (S) - 索托激活至关重要.
结论:
- 这项研究成功地阐明了sotolone enantiomers的差异性嗅觉感知和受体相互作用.
- OR8D1对索托具有显著的反选择性,其中 (S) - 索托是一种更强大的激活剂.
- 特定的氨基酸残留物,特别是N2065·46,对于 (S) -sotolone对OR8D1的酶选择性识别和激活是不可或缺的.
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