Comparison on the conformation folding and structure change of serum albumin induced by methyl parathion and its metabolite p-nitrophenol

Abstract

Residues of organophosphorus pesticides (OPPs) and their metabolites pose potential risks to the environment and human health. In the work, multiple spectroscopy, atomic force microscope and computational simulations were utilized to compare the interaction between methyl parathion (MP) and its metabolite p-nitrophenol (PNP) with human serum albumin (HSA). The results showed that both MP and PNP spontaneously formed complexes with HSA predominantly facilitated by hydrogen bonds and van der Waals forces, following static quenching mechanisms. The binding constant of PNP (15.16 ± 0.10 × 10⁴ L mol⁻¹) with HSA was nearly 5 times larger than that of MP (3.58 ± 0.09 × 10⁴ L mol⁻¹), suggesting PNP had a stronger affinity with HSA, which was consistent with density functional theory (DFT) calculation. Molecular docking revealed that the binding energy of PNP (−4.54 kcal mol⁻¹) was lower than that of MP (−4.07 kcal mol⁻¹), which potentially contributed a longer in vivo half-life of PNP and greater potential harm. Moreover, synchronous, 3D, FTIR and CD spectroscopy analyses indicated that the binding of MP and PNP to HSA significantly altered the microenvironment of amino acid residues and the secondary structure of HSA. Molecular dynamics simulations further demonstrated these findings. The study provides insights on the interaction between the pesticide MP and its metabolite PNP with HSA, which help understand the impact of pesticide residues on the food safety and environmental protection at the molecular level.