Abstract
Background: Deltamethrin (DLM) is a commercial insecticide of the synthetic pyrethroid family that is used to control disease-causing insects and vectors. When humans are exposed to the fumes or aerosols of DLM, it enters the body via cuticular absorption and reacts with proteins and other biomolecules.
Objective: Alpha-2-macroglobulin (α2M) is a serum proteinase inhibitor that also carries out receptor- mediated endocytosis of extracellular substances. This study was done to decipher the structural and functional alterations of α2M by DLM.
Methods: Various spectroscopic techniques, including UV absorption and fluorescence spectroscopy, binding studies, and molecular docking, were used to characterize the interaction of DLM with α2M. The affinity constant was calculated from the Stern-Volmer equation using fluorescence data.
Results: The UV-Vis and fluorescence spectral studies indicated the formation of a complex between α2M and DLM. Thermodynamically, the interaction was found to be spontaneous with ΔG = -4.23 kcal/mol. CD spectra suggested a change in the secondary structure of the protein from β to α helical content with increasing concentration of DLM. The molecular docking study by Autodock Vina established the interaction of DLM with Glu-926, Ala-1103, Ala-1108, Val-1116, Asn-1159, Glu-1220, Leu-1261, Thr-1272, Ile-1390, Pro-1391, Lys-1393, Val-1396, Lys-1397, Thr-1408, Glu-1409, Val-1410, Ser-1411, Ser-1412, and Asn-1413 with an improved docking score of -6.191 kcal/mol. The binding was carried out in the vicinity of the receptor-binding domain at the C-terminal of α2M.
Conclusion: The decrease in the functional activity and structural changes of protein after binding with DLM has a significant effect on human α2M. The information may be useful for exploring the role of DLM in a clinical chemistry laboratory.
Keywords: Synthetic pyrethroids, deltamethrin, insecticide, alpha-2-macroglobulin, anti-proteinase, molecular docking.
Graphical Abstract
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