Research on the discrepant inhibition mechanism of microcystin-LR disinfectant by-products target to protein phosphatase 1.

The secondary contamination for microcystin disinfection by-products (MC-DBPs) is of concern due to the residual toxic structure similar to their original toxins. To evaluate the toxicity of MC-DBPs, the discrepant inhibition mechanisms target to protein phosphatase 1 (PP1) were evaluated. Five typical MCLR-DBPs related to the oxidation of Adda were identified as CHNOCl (+1Cl1OH, P1/P2), CHNO (+2OH, P3/P4), and CHNO (P5). Toxicity inhibition experiment on PP1 showed that the toxicity was in the sequence of MCLR > P3 > P1 > P4 > P2 > P5. Base on MOE molecular simulation, the discrepant inhibition mechanisms for MCLR and MCLR-DBPs target to PP1 were further clarified. The combination of MCLR/MCLR-DBPs to PP1 was mainly restrained by residues Adda and Arg. Above key sites promoted the binding of MCLR/MCLR-DBPs to PP1 through the hydrogen bonds (HO ← Adda, Tyr → Adda, HO ← Arg, Tyr → Arg, Glu ← Arg), ionic bonds (Asp-Adda, Glu-Arg, Asp → Arg), and H-pi bonds (Trp ↔ Adda, Ser ↔ Adda). The oxidation of Adda also affected Mdha participated ionic bond Glu-Mdha and Glu participated hydrogen bond HO → Glu. Besides, the "integral hydrogen bonds and ionic bonds" between toxin and PP1 also had important effects on the toxin toxicity. In this way, the inhibition of "Adda destroyed" MC-DBPs target to PP1 was regulated.