In vitro and in silico investigations of the binding interactions between chlorophenols and trypsin.
In vitro and in silico investigations of the binding interactions between chlorophenols and trypsin.
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DOI：
10.1016/j.jhazmat.2014.05.092
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发表时间：
2014-08
影响因子：
13.6
通讯作者：
Yanqing Wang;Chunjian Tan;Shulin Zhuang;P. Zhai;Yun Cui;Qiu-hua Zhou;Hong-Mei Zhang;Z. Fei
中科院分区：
文献类型：
--
作者：
Yanqing Wang;Chunjian Tan;Shulin Zhuang;P. Zhai;Yun Cui;Qiu-hua Zhou;Hong-Mei Zhang;Z. Fei
氯酚类化合物是一级有毒污染物，具有潜在的致癌、致突变活性和毒性。由于胰蛋白酶是许多外源性环境污染物的主要结合靶点，而氯酚类化合物与胰蛋白酶的分子相互作用研究还很缺乏，因此采用多光谱技术和分子模拟相结合的方法，研究了2-CP、2，6-DCP、2，4，6-TCP、2，4，6-TCP、2，3，4，6-TCP和PCP等5种氯酚类化合物与胰蛋白酶的结合作用。氯酚结合在胰蛋白酶的一个主要位点上，这种结合引起胰蛋白酶微环境和整体构象的变化。不同氯原子数的氯离子对结合有显著影响，其结合常数KA的大小顺序为KA（2-CP）<KA（2，6-DCP）> KA（2，4，6-TCP）<KA（2，3，4，6-TCP）<KA（PCP）。这些氯酚类化合物与胰蛋白酶的相互作用主要通过疏水相互作用、氢键相互作用和芳香-芳香π-π堆积相互作用进行。本研究结果为深入了解氯酚类化合物与胰蛋白酶的结合机理提供了重要信息，并为氯酚类化合物对人体健康的潜在毒性风险提供了重要信息。
Being the first-degree toxic pollutants, chlorophenols (CP) have potential carcinogenic and mutagenic activity and toxicity. Since there still lacks studies on molecular interactions of chlorophenols with trypsin, one major binding target of many exogenous environmental pollutants, the binding interactions between five chlorophenols, 2-CP, 2,6-DCP, 2,4,6-TCP, 2,4,6-TCP, 2,3,4,6-TCP and PCP and trypsin were characterized by the combination of multispectroscopic techniques and molecular modeling. The chlorophenols bind at the one main site of trypsin and the binding induces the changes of microenvironment and global conformations of trypsin. Different number of chloride atoms significantly affects the binding and the binding constantsKAranks asKA(2-CP) <KA(2,6-DCP) ≈KA(2,4,6-TCP) <KA(2,3,4,6-TCP) <KA(PCP). These chlorophenols interacts with trypsin mainly through hydrophobic interactions and via hydrogen bonding interactions and aromatic–aromatic π–π stacking interaction. Our results offer insights into the binding mechanism of chlorophenols with trypsin and provide important information for possible toxicity risk of chlorophenols to human health.