Probing the potential toxicity by characterizing the binding mechanism of sodium dehydroacetate to human serum albumin
Probing the potential toxicity by characterizing the binding mechanism of sodium dehydroacetate to human serum albumin
复制标题
通过表征脱氢乙酸钠与人血清白蛋白的结合机制探讨潜在毒性
DOI：
10.1002/jsfa.11712
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发表时间：
2021
影响因子：
4.1
通讯作者：
Wansong Zong
中科院分区：
文献类型：
--
作者：
Mengchen Xu;Zhaohao Cui;Yihua Xiao;Changqing Liu;Rutao Liu;Wansong Zong
研究背景脱氢醋酸钠（DHA‐S）是一种常见的食品添加剂，可与血浆中的血清蛋白联合收割机结合，但DHA‐S与人血清白蛋白（HSA）的相互作用机制尚不清楚。本研究采用多种光谱技术、等温滴定量热法（ITC）、分子对接和酯酶活性测试等方法研究了DHA‐S与人血清白蛋白（HSA）的相互作用机制，发现DHA‐S与HSA形成了双硫代TSA DHA‐S-HSA复合物，并改变了HSA的结构。由于DHA-S改变了色氨酸（Trp）所在的疏水亚结构域IIA的紧密结构，因此HSA微环境的疏水性增强。随着DHA‐S的加入，HSA的骨架结构变得松散，HSA表面的溶剂壳被破坏。DHA‐S改变了HSA的二级结构，导致α-螺旋减少和β-折叠含量增加。该相互作用是放热的，自发的，由货车范德华力和氢键驱动。DHA‐S抑制HSA的酯酶活性。分子对接结果表明，DHA‐S与HSA的结合位点位于IIA和IIIA亚结构域的空腔内，但与HSA酯酶活性相关的氨基酸不在结合口袋内，表明DHA‐S抑制HSA酯酶活性的机制是蛋白质结构的改变。该研究有助于了解DHA-S的毒性，并为食品添加剂的安全使用提供基础数据。© 2021化学工业协会
BACKGROUNDSodium dehydroacetate (DHA‐S) is a common food additive, which can combine with serum proteins in the plasma, but the interaction mechanism between DHA‐S and human serum albumin (HSA) is unclear. In this study, multiple spectroscopy techniques, isothermal titration calorimetry (ITC), molecular docking and esterase activity test were employed to investigate the interaction mechanism of DHA‐S and HSA.RESULTSA DHA‐S–HSA complex was formed and the structure of HSA were altered by DHA‐S. Since DHA‐S changed the tight structure of the hydrophobic subdomain IIA where tryptophan (Trp) was placed, the hydrophobicity of the microenvironment of HSA was enhanced. With the addition of DHA‐S, the skeleton structure of HSA became loose and the solvent shell on the HSA surface was destroyed. DHA‐S altered the secondary structure of HSA, resulting in the decreased α‐helix and increased β‐sheet contents. The interaction was exothermic and spontaneous driven by van der Waals and hydrogen bonding. DHA‐S inhibited the esterase activity of HSA. Molecular docking demonstrated that the binding site of DHA‐S on HSA located at the cavity of subdomains IIA and IIIA, but the amino acids related to esterase activity of HSA were not in the binding pocket, indicating that the mechanism by which DHA‐S inhibited HSA esterase activity was the change in protein structure.CONCLUSIONThis study illustrated that DHA‐S interacted with HSA and the structure and function of HSA were affected by DHA‐S. This research could help to understand the toxicity of DHA‐S and provide basic data for safe use of food additives. © 2021 Society of Chemical Industry