Interaction of organophosphate pesticide chlorpyrifos with alpha-2-macroglobulin: Biophysical and molecular docking approach

ABSTRACT

Organophosphate class of pesticides causes neurotoxicity and carcinogenicity in humans. Once inside the human body, these pesticides often interact with plasma proteins, such as alpha-2-macroglobulin (α₂M) which is the key anti-proteinase. Our work focuses on the structural and functional alteration of α₂M by chlorpyrifos (CPF), a member of organophosphates. We explored the binding interaction between alpha-2-macroglobulin and CPF by using UV absorption and fluorescence spectroscopy (steady state and synchronous), circular dichroism and molecular docking approach. The functional activity of α₂M was analyzed by anti-proteinase trypsin inhibitory assay which showed dose-dependent decrease in alpha-2-macroglobulin antiproteolytic potential. UV absorption studies and fluorescence quenching experiments suggested the formation of a complex between α₂M and CPF. The CD spectra suggested a reduction in the beta helical (β helix) content of α₂M. Analysis of thermodynamic parameters suggested the process is spontaneous and endothermic with the ΔG and ΔH values being −5.501 kJ/mol, 11.49 kJ/mol, respectively. CPF binds with Ile-1390, Pro-1391, Leu-1392, Lys-1393, Val-1396, Lys-1397, Arg-1407, Thr-1408, Glu-1409, Val-1410, Asp-282, Glu-281 of α₂M as suggested by molecular docking.

KEYWORDS:

• Chlorpyrifos
• proteinase inhibitor
• alpha-2-macroglobulin
• insecticides
• thermodynamic change

Acknowledgments

The authors acknowledge the research facilities provided by the Department of Biochemistry, Aligarh Muslim University, Aligarh. SD is thankful to Indian Council of Medical Research (ICMR), New Delhi for providing SRF fellowship.

Disclosure statement

The authors declare that there is no conflict of interest.

Additional information

Funding

The authors acknowledge the research facilities provided by the Department of Biochemistry, Aligarh Muslim University, Aligarh. SD is thankful to Indian Council of Medical Research (ICMR), New Delhi for providing SRF fellowship.