Water‐Regulated Mechanisms for Degradation of Pesticides Paraoxon and Parathion by Phosphotriesterase: Insight from QM/MM and MD Simulations
Yuzhuang Fu, Fangfang Fan, Binju Wang, Zexing Cao
Abstract
Abstract The enzymatic degradation of pesticides paraoxon (PON) and parathion (PIN) by phosphotriesterase (PTE) has been investigated by QM/MM calculations and MD simulations. In the PTE‐PON complex, Zn α and Zn β in the active site are five‐ and six‐coordinated, respectively, while both zinc ions are six coordinated with the Zn α ‐bound water molecule (WT1) for the PTE‐PIN system. The hydrolytic reactions for PON and PIN are respectively driven by the nucleophilic attack of the bridging‐OH − and the Zn α ‐bound water molecule on the phosphorus center of substrate, and the two‐step hydrolytic process is predicted to be the rate‐limiting step with the energy spans of 13.8 and 14.4 kcal/mol for PON and PIN, respectively. The computational studies reveal that the presence of the Zn α ‐bound water molecule depends on the structural feature of substrates characterized by P=O and P=S, which determines the hydrolytic mechanism and efficiency for the degradation of organophosphorus pesticides by PTE.