Novel evidence on iodoacetic acid-induced immune protein functional and conformational changes: Focusing on cellular and molecular aspects,Science of the Total Environment

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Novel evidence on iodoacetic acid-induced immune protein functional and conformational changes: Focusing on cellular and molecular aspects
Science of the Total Environment ( IF 8.2 ) Pub Date : 2023-12-15 , DOI: 10.1016/j.scitotenv.2023.169359
Shuqi Guo ₁ , Falin He ₁ , Shaoyang Hu ₁ , Wansong Zong ₂ , Rutao Liu ₁

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Elevated levels of iodide occur in raw water in certain regions, where iodination disinfection byproducts are formed during chloramine-assisted disinfection of naturally iodide-containing water. Iodoacetic acid (IAA) is one of the typical harmful products. The mechanisms underlying IAA-induced immunotoxicity and its direct effects on biomolecules remained unclear in the past. Cellular, biochemical, and molecular methods were used to investigate the mechanism of IAA-induced immunotoxicity and its binding to lysozyme. In the presence of IAA, the cell viability of coelomocytes was significantly reduced to 70.8 %, as was the intracellular lysozyme activity. Upon binding to IAA, lysozyme underwent structural and conformational changes, causing elongation and unfolding of the protein due to loosening of the backbone and polypeptide chains. IAA effectively quenched the fluorescence of lysozyme and induced a reduction in particle sizes. Molecular docking revealed that the catalytic residue, Glu 35, which is crucial for lysozyme activity, resided within the docking range, suggesting the preferential binding of IAA to the active site of lysozyme. Moreover, electrostatic interaction emerged as the primary driving force behind the interaction between IAA and lysozyme. In conclusion, the structural and conformational changes induced by IAA in lysozyme resulted in impaired immune protein function in coelomocytes, leading to cellular dysfunction.

中文翻译：

关于碘乙酸诱导的免疫蛋白功能和构象变化的新证据：关注细胞和分子方面

部分地区原水中碘化物含量升高，对天然含碘水进行氯胺辅助消毒时会产生碘化消毒副产物。碘乙酸(IAA)是典型的有害产物之一。 IAA 诱导免疫毒性的机制及其对生物分子的直接影响过去仍不清楚。采用细胞、生化和分子方法研究IAA诱导的免疫毒性机制及其与溶菌酶的结合。在 IAA 存在下，体腔细胞的细胞活力显着降低至 70.8%，细胞内溶菌酶活性也显着降低。与 IAA 结合后，溶菌酶发生结构和构象变化，由于主链和多肽链松弛，导致蛋白质伸长和展开。 IAA 有效猝灭溶菌酶的荧光并诱导粒径减小。分子对接显示，对溶菌酶活性至关重要的催化残基 Glu 35 位于对接范围内，表明 IAA 优先与溶菌酶的活性位点结合。此外，静电相互作用成为 IAA 和溶菌酶之间相互作用的主要驱动力。总之，IAA在溶菌酶中诱导的结构和构象变化导致体腔细胞中的免疫蛋白功能受损，导致细胞功能障碍。

更新日期：2023-12-15

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