Research on the discrepant inhibition mechanism of microcystin-LR disinfectant by-products target to protein phosphatase 1
Research on the discrepant inhibition mechanism of microcystin-LR disinfectant by-products target to protein phosphatase 1
复制标题
微囊藻毒素-LR消毒剂副产物对蛋白磷酸酶1的差异抑制机制研究
DOI：
10.1007/s11356-021-12472-1
复制
发表时间：
2021-04-19
影响因子：
5.8
通讯作者：
Zong, Wansong
中科院分区：
文献类型：
--
作者：
Hu, Zhengxin;Wang, Xiaoning;Zong, Wansong
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 C49H75N10O13Cl (+1Cl1OH, P1/P2), C34H54N10O12 (+2OH, P3/P4), and C49H76N10O14 (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 (H2O Adda(5), H2O Arg(4), Glu(275) 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 H2O -> 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.
