对羟基杏仁酸合成酶三维结构模建及其与底物的分子对接研究

以对羟基苯丙酮酸双氧化酶(HPPD)的晶体结构为模板, 利用同源模建方法构建了与其高度同源、底物相同但催化功能存在明显差别的对羟基杏仁酸合成酶(HMS)的三维结构, 并对模建结构的合理性进行了分析. 在模建结果的基础上, 对HPPD和HMS分别与底物羟苯基丙酮酸(HPP)进行分子对接计算, 比较了二者结合模式的异同, 为两种同源酶在催化方面差异性的合理阐释提供了一些有益的信息.

Homology Modeling of p-Hydroxymandelate Synthase and Its Molecular Docking with Substrate

p-hydroxymandelate synthase (HMS) and 4-hydroxyphenylpyruvate dioxygenase (HPPD) are highhomology and share the same substrate, p-hydroxyphenylpyruvate (HPP). Using HPPD as a structural template , the3D structure of HMS was built by homology modeling. Rational analysis of the modeled structure was performed.Subsequently, docking calculations of HPPD and HMS with the substrate HPP were conducted. A comparison ofthe binding mode of these two enzymes with HPP was made. While the three residues that coordinate to Fe2 , His,His and Glu, are important for the tight binding of both enzymes with the substrate, the conserved residues near thesubstrate, Leu228, Pro243, Asn245 and Phe364 in HPPD(1T47) and Met187, Thr202 and Ile204 in HMS, play acrucial role in determination of the reaction pathway. This may provide a starting point for the understanding oftheir difference in catalytic function.