Fluorometric and molecular modeling deciphering the non-covalent interaction between cyromazine and human serum albumin
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Cyromazine (CMZ) had been believed to be one of the safest pesticides and widely used for many years until its carcinogenesis was revealed recently. In this work, the interaction between cyromazine and human serum albumin (HSA) was systematically investigated by multiple spectroscopic methods and molecular docking techniques using warfarin and flufenamic acid as probes. The results demonstrated the fluorescence of HSA had been quenched by CMZ through static mechanism, with new non-covalent complexes formed at ground state. Fluorescence probe experiments indicated CMZ bound to Sudlow’s site I in subdomain IIA of HSA, having no competition with site marker in site II. The number of binding sites, equilibrium constants and thermodynamic parameters were calculated by monitoring the binding equilibriums at different temperatures. The positive enthalpy change (ΔH θ) and entropy change (ΔS θ) implied the binding was mainly conducted by hydrophobic interactions. The binding was an endothermic, spontaneous (ΔG θ < 0) and entropy-driven process which made the energy distribution of the system more evenly. The force of interaction and the conformation of binding pocket were displayed by molecular simulation and discussed at molecular level. Circular dichroism (CD) spectra indicated distorted α-helix content of HSA decreased while other fine secondary structure increased when CMZ was added.
KeywordsCyromazine Protein-binding Fluorescence probe Molecular docking Thermodynamics
The authors gratefully acknowledge the fund support from Research Foundation of Education Bureau of Hubei Province of China (D20174301, T201719), Superior Subjects Project of Jingchu University of Technology (17020303), Hubei Natural Science Foundation (2016CFB149) and Scientific Research Project of Jingchu University of Technology (QN201601, ZR201509).
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