化学
诺比林
圆二色性
脂肪酶
黄酮类
酶动力学
立体化学
胰脂肪酶
分子模型
酶
动力学
IC50型
疏水效应
分子动力学
生物物理学
生物化学
活动站点
体外
类黄酮
计算化学
色谱法
生物
物理
抗氧化剂
量子力学
作者
Xin Huang,Junxiang Zhu,Li Wang,Huijuan Jing,Chaoyang Ma,Xingran Kou,Hongxin Wang
标识
DOI:10.1016/j.ijbiomac.2020.07.305
摘要
This study aimed to reveal the interaction and inhibitory mechanisms of tangeretin (TAN), nobiletin (NBT), and their acidic hydroxylated forms, 5-demethyltangeretin (5-DT) and 5-demethylnobiletin (5-DN) on porcine pancreatic lipase (PPL) using spectroscopic techniques and molecular dynamics (MD) simulation. PPL inhibition assay showed that the inhibitory activity of NBT (IC50 value of 3.60 ± 0.19 μM) was superior to those of three polymethoxylated flavones (PMFs), indicating it may be related to the methoxy groups at the 3′-position in its molecular structure. Inhibition kinetic analyses demonstrated that the inhibition types of the 4 PMFs were consistent with the mixed inhibition model, which agreed well with the results from the ultraviolet-visible (UV–Vis) spectroscopy, Circular dichroism (CD), fluorescence spectroscopy, molecular docking, and MD simulation that PMFs could bind to the PPL catalytic site and non-catalytic site, affecting the normal spatial conformation of PPL and weakening its ability to decompose the substrate. All these findings suggest that PMFs are a kind of natural lipase inhibitors, and NBT has the potential as a lipase inhibition precursor because of its unique flavone skeleton structure.
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