College of Geography and Environment, Shandong Normal University, 88# East Wenhua Road, Jinan, 250014, Shandong, China.
School of Environmental and Civil Engineering, Jiangnan University, 1800# Lihu Avenue, Wuxi, 214122, Jiangsu, China.
Environ Sci Pollut Res Int. 2018 Sep;25(26):26020-26029. doi: 10.1007/s11356-018-2676-9. Epub 2018 Jul 2.
Biotransformation was an important pathway to regulate the toxicity of microcystins (MCs) targeted to protein phosphatases (PPs). To explore the regulation effectiveness and mechanism, several typical biothiol transformation products originated from MCLR were prepared by nucleophilic addition reaction. The reduced inhibition effect of MCLR transformation products on PP1 was evaluated and compared with their original toxin. Though molecular simulation showed the introduced biothiols enhanced the total combination areas and energies for target complexes, the steric hindrance of introduced biothiols inhibited the combination between the key action sites (Mdha and Adda residues) and PP1. Furthermore, the introduced biothiols also weakened the hydrogen bonds for some key interaction sites and altered the ion bonds between PP1 and the two Mn ions in the catalytic center. The discrepant regulation effect for biothiols on the toxicity of MCLR was closely related to above indexes and influenced by molecular sides.
生物转化是调节针对蛋白磷酸酶（PPs）的微囊藻毒素（MCs）毒性的重要途径。为了探索调节效果和机制，通过亲核加成反应制备了几种源自 MCLR 的典型生物硫转化产物。评估了 MCLR 转化产物对 PP1 的还原抑制作用，并将其与原始毒素进行了比较。尽管分子模拟表明引入的生物硫醇增加了靶复合物的总结合面积和能量，但引入的生物硫醇的空间位阻抑制了关键作用位点（Mdha 和 Adda 残基）与 PP1 之间的结合。此外，引入的生物硫醇还削弱了一些关键相互作用位点的氢键，并改变了 PP1 与催化中心两个 Mn 离子之间的离子键。生物硫醇对 MCLR 毒性的不同调节作用与上述指标密切相关，并受分子侧面的影响。
