Attenuation of Lysozyme's Lytic Activity: Impact of Organochlorine Pesticide Through Modulating the Structure and Binding Site via Allosteric Interactions.

Pesticides play a crucial role in protecting crops from pests, ensuring food security and higher agricultural yields. However, excessive pesticide use can harm human health, disrupt ecosystems, and contaminate soil and water sources. Endosulfan, a potent organochlorine pesticide, presents severe toxicological risks, manifesting as nausea, emesis, vertigo, cephalalgia, cognitive impairment, convulsions, and, in extreme cases, mortality. Owing to its extensive utilization in agriculture, it demonstrates a high propensity for vegetable contamination. The present investigation elucidates the molecular interplay between endosulfan and lysozyme, a protein particularly susceptible to its perturbative effects. Notably, an ADMET analysis confirms the facile permeation of endosulfan across the blood-brain barrier (BBB), underscoring its neurotoxic potential. Our findings reveal that while the overarching secondary structural integrity of lysozyme remains ostensibly preserved, its active site undergoes substantial perturbation upon endosulfan exposure. Despite its initial interaction at an allosteric site, the pesticide induces destabilization of key active-site residues, leading to a partial attenuation of enzymatic activity. Spectroscopic analyses indicate that endosulfan directly associates with Trp63, eliciting a subtle quenching effect in the fluorescence spectrum. However, this quenching is unequivocally attributable to static mechanisms, as substantiated by an increase in absorbance spectra coupled with an unaltered fluorescence lifetime. Moreover, this allosteric interaction profoundly modulates the protein's functional dynamics through allosteric perturbation propagation. Allosteric coupling intensity (ACI) analysis further delineates that His15 and Val92 experience significant perturbation, with ACI values exceeding 0.9, a phenomenon consistently observed in both the bound and unbound states. This underscores the pervasive influence of endosulfan on lysozyme's conformational stability and functional integrity.