Investigations on the binding properties of hydroxylated polybrominated diphenyl ethers with lysozyme using the multispectral techniques and molecular modeling

Abstract

As a kind of phenolic chemical with endocrine disrupting potency, hydroxylated polybrominated diphenyl ethers (OH-PBDEs) cause a latent threat to human health from their residue in the environment. Their binding efficiency with lysozyme (LYSO) was studied by molecular simulation combined with fluorescence, UV-vis absorption and circular dichroism (CD), so as to assess their toxicity at the molecular level. Molecular docking data indicate that van der Waals force is the principal interaction force between OH-PBDEs and LYSO. The binding site for 5'-OH-BDE-25 in LYSO is ascertained as the active site, which interaction with the TRP63 and TRP108 residues of LYSO to take shape a strong face-to-face stacked rank (F-shaped). Both 4'-OH-BDE-99 and 3'-OH-BDE-154 display a certain degree of deviation from the active site. Nevertheless, their F-shaped interaction with TRP63 conduce to bind LYSO and stabilize the docking conformation. Combined with dynamics simulation and spectral analysis, the secondary structure of LYSO can be induced by the three kinds of OH-PBDEs. CD spectrum shows that the combination of LYSO and OH-PBDEs will make α- Helix content increased. The combination of OH-PBDEs and LYSO touch upon a static quenching mechanism as a result of steady state fluorescence. The energy decomposition analysis exhibited that LYSO-OH-PBDEs binding site was stable by van der Waals and hydrophobic interaction. As enzyme activity experiments demonstrate that OH-PBDEs can inhibit the activity of LYSO, which is helpful to clarify the molecular toxicity mechanism of OH-PBDEs.

Keywords: Binding free energy; Hydroxylated polybrominated diphenyl ethers; Lysozyme; Molecular modeling; Spectroscopy.