Assessment of binding potencies of polychlorinated biphenyls and polybrominated diphenyl ethers with Baikal seal and mouse constitutive androstane receptors: Comparisons across species and congeners
| Autor: | Pham Thi Dau, Hiroki Sakai, Le Huu Tuyen, Masashi Hirano, Eun-Young Kim, Hiroshi Ishibashi, Hisato Iwata |
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| Rok vydání: | 2021 |
| Předmět: |
education.field_of_study
Environmental Engineering Stereochemistry Seals Earless Population Polybrominated Biphenyls Pollution Polychlorinated Biphenyls Orders of magnitude (mass) Dissociation constant Transactivation chemistry.chemical_compound Mice Polybrominated diphenyl ethers chemistry Constitutive androstane receptor Halogenated Diphenyl Ethers Environmental Chemistry Animals Androstane Environmental Pollutants Receptor education Waste Management and Disposal |
| Zdroj: | The Science of the total environment. 806(Pt 3) |
| ISSN: | 1879-1026 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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