Structural and Functional Alterations of Human Serum Albumin (HSA) Induced by TBBPS-BME: A Spectroscopic, Computational, and Molecular Dynamics Study

Abstract

Tetrabromobisphenol S Dimethyl Ether (TBBPS-BME) serves as a substitute for Tetrabromobisphenol A (TBBPA). It exhibits a greater potential for bioaccumulation, potentially posing substantial risks to environmental health and human safety. This research utilized a variety of spectroscopic and computational modeling methods to investigate structural and functional alterations of human serum albumin (HSA) induced by TBBPS-BME. The findings revealed that TBBPS-BME induces fluorescence quenching in HSA by binding to site I. The predominant force in this binding process is hydrophobic interaction. The binding constant for this complex is 2.394 ± 0.032 × 10⁴ M^-1 at 298 K, suggesting that they can form complex in vivo. The interaction with TBBPS-BME causes structural alterations in HSA, leading to a decrease in α-helix proportion and an overall enhancement of protein structural flexibility. The esterase-like function of HSA was also impacted by the presence of TBBPS-BME. Computational simulation tests indicate that this may be through interactions with residues Lys199 and Lys195. Molecular dynamics simulations further validated the formation of stable TBBPS-BME-HSA binary complexes, highlighting the critical role of hydrogen bonds in this steadiness. Alanine scanning mutation analysis revealed that Trp214, Phe211, Arg218, Lys199, and His242 are necessary for the assembly of the TBBPS-BME-HSA complex. Overall, this study provides an exhaustive examination of the binding mechanisms between TBBPS-BME and HSA, elucidating the underlying health hazards that may arise from exposure to TBBPS-BME.