Mechanism for the Potential Inhibition Effect of Microcystin-LR Disinfectant By-Products on Protein Phosphatase 2A.

ABSTRACT: The secondary contamination of microcystin disinfection by-products (MC-DBPs) is of concern due to the residual structure similar to their original toxin. Based on identification and preparation, the potential inhibition effect of typical MCLR-DBPs (associated with the oxidation of Adda⁵) on PP2A was confirmed in the sequence of MCLR > P1 > P4 > P3 ≈ P2 > P7 ≈ P6 ≈ P5 > P8. To elucidate the molecular mechanism underlying the inhibition effect, the interaction models for typical MCLR-DBPs and PP2A were constructed using a modeling-based-on-ligand-similarity approach, and the candidate interaction parameters between typical MCLR-DBPs and PP2A were obtained by molecular docking. By analyzing the correlation between inhibition data and candidate interaction parameters, the key interaction parameters were filtered as hydrogen bonds "Adda⁵"←Asn₁₁₇, "Adda⁵"←His₁₁₈, MeAsp³←Arg₈₉, Arg⁴←Arg₂₁₄, Arg⁴→Pro₂₁₃; ionic bonds Glu⁶-Arg₈₉, Asp₈₅-Mn₁²⁺, Asp₅₇-Mn₂²⁺; and metal bonds Glu⁶-Mn₁²⁺, Glu⁶-Mn₂²⁺. With the gradual intensification of chlorination, Adda⁵ was destroyed to varying degrees. The key interactions changed correspondingly, resulting in the discrepant inhibition effects of typical MCLR-DBPs on PP2A.

SUBMITTER: Yu H 

PROVIDER: S-EPMC9780900 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature