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 5 were identified as C 49 H 75 N 10 O 13 Cl (+1Cl1OH, P1/P2), C 34 H 54 N 10 O 12 (+2OH, P3/P4), and C 49 H 76 N 10 O 14 (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 5 and Arg 4 . Above key sites promoted the binding of MCLR/MCLR-DBPs to PP1 through the hydrogen bonds (H 2 O ← Adda 5 , Tyr 134 → Adda 5 , H 2 O ← Arg 4 , Tyr 134 → Arg 4 , Glu 275 ← Arg 4 ), ionic bonds (Asp 197 –Adda 5 , Glu 275 –Arg 4 , Asp 220 → Arg 4 ), and H-pi bonds (Trp 206 ↔ Adda 5 , Ser 129 ↔ Adda 5 ). The oxidation of Adda 5 also affected Mdha 7 participated ionic bond Glu 275 –Mdha 7 and Glu 6 participated hydrogen bond H 2 O → Glu 6 . 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 5 destroyed” MC-DBPs target to PP1 was regulated.