Assessment of binding potencies of polychlorinated biphenyls and polybrominated diphenyl ethers with Baikal seal and mouse constitutive androstane receptors: Comparisons across species and congeners.
Assessment of binding potencies of polychlorinated biphenyls and polybrominated diphenyl ethers with Baikal seal and mouse constitutive androstane receptors: Comparisons across species and congeners.
复制标题
评估多氯联苯和多溴二苯醚与贝加尔海豹和小鼠组成型雄甾烷受体的结合效力：物种和同系物之间的比较。
DOI：
10.1016/j.scitotenv.2021.150631
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发表时间：
2022
影响因子：
9.8
通讯作者：
Iwata H.
中科院分区：
文献类型：
--
作者：
Dau PT;Ishibashi H;Tuyen LH;Sakai H;Hirano M;Kim EY;Iwata H.
用表面等离子体共振(SPR)生物传感器测定了多氯联苯(PCbs)和多溴联苯醚(PBDEs)与Baikal海豹(BsCAR_LBD)和小鼠(MCAR_LBD)的雄烷受体(CAR)配体结合域(LBD)的结合势能(平衡解离常数Kd)。单个同系物与mCAR_LBD的结合亲和力趋于高于与bsCAR_LBD的结合亲和力，但差异在相同的数量级内。在电子对接模拟中，多溴二苯醚与两种CAR_LBD中特定氨基酸残基的非共价相互作用比与多氯联苯中特定氨基酸残基的结合亲和力更强，这支持了它们结合亲和力的结果。同系物之间的结合亲和力比较揭示了更高结合的结构要求；多氯联苯的一氯或二邻位、三偏位和二对位氯取代，以及多溴联苯的二位或三邻位、一偏位和二对位溴取代。这些同系物的结合能力不太可能解释之前报道的CAR介导的反式激活能力，这意味着它们的反式激活是以配体依赖的方式调节的，但与配体结合的方式不同。风险评估分析表明，在野生贝加尔海豹种群中，个体多氯联苯和多溴二苯醚的KD值比各自肝脏中的浓度高出1-4个数量级。
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 silicodocking 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 diortho-, trimeta-, and dipara‑chlorine substitutions for PCBs, and di or triortho-, monometa-, and dipara‑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 theKDvalues of individual PCB and PBDE congeners were 1-4 orders of magnitude higher than their respective hepatic concentrations in wild Baikal seal population.