The molecular interaction of three haloacetic acids with bovine serum albumin and the underlying mechanisms

Abstract

As typical disinfection byproducts, monohaloacetic acids (monoHAAs) were reported to be cytotoxic and genotoxic with the order of iodoacetic acid (IAA) > bromoacetic acid (BAA) ≫ chloroacetic acid (CAA). However, it remains unknown for the toxicity of monoHAAs to biomacromolecules and the detailed molecular mechanisms. Consequently, the structural and functional responses of bovine serum albumin (BSA) to three monoHAAs (CAA, BAA and IAA) were compared by investigating their interactions using multi-spectroscopic methods, esterase-like activity assays and molecular docking simulations. Results found that monoHAAs stimulated the esterase-like activity of BSA to different levels with the order of CAA > IAA > BAA. The binding of monoHAAs affected the secondary structures, peptide skeleton and aggregation state of BSA. The interactions of BSA with CAA, BAA and IAA are dominated by van der Waals forces and hydrogen bonds, hydrophobic forces and electrostatic forces, respectively. The binding of CAA directly interferes the key residues Arg 254 and Tyr 147 to the activity but BAA and IAA do not. BAA and IAA interacted with Tyr residues by static and dynamic quenching, respectively. The binding constant suggested a relatively weak binding affinity for the interaction of BSA with BAA and with IAA. While CAA barely changed the fluorescence of BSA with the increase of exposure concentrations. Accordingly, this study provides a comprehensive view on the molecular toxicity of monoHAAs interacting with BSA.