Inhibition of Pancreatic Elastase by Polyphenolic Compounds
Inhibition of Pancreatic Elastase by Polyphenolic Compounds
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DOI：
10.1021/jf1017934
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发表时间：
2010-10-13
影响因子：
6.1
通讯作者：
Do Freitas, Victor
中科院分区：
文献类型：
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作者：
Bras, Natercia F.;Goncalves, Rui;Do Freitas, Victor
多酚是植物次生代谢产物，通常存在于人类饮食中，具有结合和抑制消化蛋白的能力。以Suc-（Ala）（3）-对硝基苯胺为底物，多酚类化合物为抑制剂，测定了猪胰弹性蛋白酶（PPE）的动力学活性。多酚聚合度和多酚抑制PPE的能力之间的正相关关系进行了观察。具有至少1154 Da的分子量的原花青素是观察到显著抑制能力所必需的。动力学参数也被计算，并证实抑制是可逆的和竞争性的。分子对接和动力学模拟表明，四聚体结构具有更高的亲和力，酶由于建立更多的接触点与氨基酸存在于其活性位点。多酚基团与残基侧链之间的氢键相互作用和疏水作用稳定并有利于该原花青素的结合模式。本工作涉及膳食单宁对消化酶活性、降低食物消化率和营养素吸收的抗营养作用的研究。一般而言，本文研究的弹性蛋白酶模型允许更好地理解多酚化合物的抑制能力。
Polyphenols are plant secondary metabolites commonly present in the human diet that possess the ability to bind and inhibit digestive proteins. In the present study, kinetic measurements of porcine pancreatic elastase (PPE) activity were determined using Suc-(Ala)(3)-p-nitroanilide as substrate and polyphenolic compounds as inhibitors. A positive relationship between the degree of polyphenol polymerization and the capacity of the polyphenols to inhibit PPE was observed. Procyanidins with a molecular weight of at least 1154 Da were necessary to observe a significant inhibitory ability. Kinetic parameters were also calculated and confirmed that the inhibition is reversible and competitive. Molecular docking and dynamics simulations demonstrated that the tetramer structure has a higher affinity to the enzyme due the establishment of more contact points with the amino acids present in its active site. Hydrogen bond interactions and hydrophobic effects established between the polyphenol groups and the side chain of residues stabilize and favor the binding mode of this procyanidin. This work is relevant to the study of the antinutritional effects caused by dietary tannins on the digestive enzymes' activity, reducing food digestibility and the absorption of nutrients. In general, the elastase model studied herein allows a better understanding of the inhibitory ability of polyphenol compounds.