Regulation on the toxicity of microcystin-LR target to protein phosphatase 1 by biotransformation pathway: effectiveness and mechanism.

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.