Assessment of binding potencies of polychlorinated biphenyls and polybrominated diphenyl ethers with Baikal seal and mouse constitutive androstane receptors: Comparisons across species and congeners

Pham Thi Dau, Hiroshi Ishibashi, Le Huu Tuyen, Hiroki Sakai, Masashi Hirano, Eun Young Kim, Hisato Iwata

Research output: Contribution to journalArticlepeer-review

Abstract

The present study evaluated the binding potencies (equilibrium dissociation constant: KD) of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) with the constitutive androstane receptor (CAR)_ligand binding domain (LBD) of the Baikal seal (bsCAR_LBD) and mouse (mCAR_LBD) using a surface plasmon resonance (SPR) biosensor. The binding affinities of individual congeners with mCAR_LBD tended to be higher than those with bsCAR_LBD but the differences were within the same order of magnitude. Notably, PBDE congeners showed higher binding affinities for both CAR_LBDs than PCB congeners. In silico docking simulations demonstrated that PBDEs had more non-covalent interactions with specific amino acid residues in both CAR_LBDs than PCBs, supporting the results of their binding affinities. Binding affinity comparisons among congeners revealed the structural requirements for higher binding; mono or di ortho-, tri meta-, and di para‑chlorine substitutions for PCBs, and di or tri ortho-, mono meta-, and di para‑bromine substitutions for PBDEs. The binding potencies of these congeners unlikely accounted for their previously reported CAR-mediated transactivation potencies, implying that their transactivation is regulated in a ligand-dependent, but a distinct manner from ligand binding. Risk assessment analysis showed that the KD values of individual PCB and PBDE congeners were 1-4 orders of magnitude higher than their respective hepatic concentrations in wild Baikal seal population.

Original languageEnglish
Article number150631
JournalScience of the Total Environment
Volume806
DOIs
Publication statusPublished - 1 Feb 2022

Keywords

  • Baikal seal
  • Constitutive androstane receptor
  • Mouse
  • Polybrominated diphenyl ethers
  • Polychlorinated biphenyls
  • Surface plasmon resonance

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