当前位置：
X-MOL 学术
›
Toxicology
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Estimating the potential toxicity of chiral diclofop-methyl: Mechanistic insight into the enantioselective behavior.
Toxicology ( IF 4.8 ) Pub Date : 2020-04-08 , DOI: 10.1016/j.tox.2020.152446 Fei Ding 1 , Wei Peng 2 , Yu-Kui Peng 3 , Bing-Qi Liu 4
Toxicology ( IF 4.8 ) Pub Date : 2020-04-08 , DOI: 10.1016/j.tox.2020.152446 Fei Ding 1 , Wei Peng 2 , Yu-Kui Peng 3 , Bing-Qi Liu 4
Affiliation
|
Chiral pollutants are widely distributed in the environment; however, the enantioselective toxic effects of these chemicals have still not fully been clarified. Using wet experiments and computational toxicology, this story was to explore the static and dynamic toxic reactions between chiral diclofop-methyl and target protein at the enantiomeric level, and further unveil the microscopic mechanism of enantioselective toxicity of chiral pesticide. Steady-state and time-resolved results indicated that both (R)-/(S)-enantiomers can form the stable toxic conjugates with target protein and the bioaffinities were 1.156 × 104 M-1/1.734 × 104 M-1, respectively, and significant enantioselectivity was occurred in the reaction. Results of the modes of toxic action revealed that diclofop-methyl enantiomers located in the subdomain IIA, and the strength of important noncovalent interactions between (S)-diclofop-methyl and the residues was greater than that of (R)-diclofop-methyl. The Gibbs free energies of the chiral reactions were －26.89/－29.40 kJ mol-1 and －25.79/－30.08 kJ mol-1, respectively, which was consistent with the outcomes of photochemistry and site-specific competitive assay. Dynamic enantioselective processes explained that the impact of intrinsic protein conformational flexibility on the toxic reaction of (R)-diclofop-methyl was lower than that of (S)-diclofop-methyl, which originates from the conformational changes and spatial displacement of the four loop regions (i.e. h6↔h7, h1↔h2, h5↔h6, and h8↔h9). The quantitative data of circular dichroism spectra confirmed such results. Energy decomposition displayed that the electrostatic energy of the target protein-(S)-diclofop-methyl system (－25.86 kJ mol-1) was higher than that of the target protein-(R)-diclofop-methyl complex (－18.21 kJ mol-1). Some crucial residues such as Lys-195, Lys-199, Ser-202, and Trp-214 have been shown to be of different importance for the enantioselective toxicity of chiral diclofop-methyl. Obviously this scenario will contribute mechanistic clues to assessing the potential hazards of chiral environmental pollutants to the body.
中文翻译：
估计手性双氯芬酸的潜在毒性：对映选择性行为的机理见解。
手性污染物在环境中分布广泛；但是，这些化学物质的对映选择性毒性作用尚未完全阐明。通过湿法实验和计算毒理学，该故事旨在探讨手性双氯氟酚-甲基与目标蛋白在对映体水平上的静态和动态毒性反应，并进一步揭示手性农药对映选择性毒性的微观机理。稳态和时间分辨结果表明，两种（R）-/（S）-对映异构体均可以与目标蛋白形成稳定的毒性缀合物，生物亲和力分别为1.156×104 M-1 / 1.734×104 M-1。反应中发生了明显的对映选择性。毒性作用模式的结果表明，位于IIA亚结构域的双氯氟甲基对映体 （S）-二氯氟甲基与残基之间重要的非共价相互作用的强度大于（R）-二氯氟甲基的残基。手性反应的吉布斯自由能分别为－26.89 / －29.40 kJ mol-1和－25.79 / －30.08 kJ mol-1，这与光化学和定点竞争分析的结果一致。动态对映选择性过程说明，内在蛋白质构象柔性对（R）-二氯氟甲基的毒性反应的影响低于（S）-二氯氟甲基的毒性反应，这是由于四个环的构型变化和空间位移引起的区域（即h6↔h7，h1↔h2，h5↔h6和h8↔h9）。圆二色性光谱的定量数据证实了这种结果。能量分解表明，目标蛋白-（S）-双氟甲基-系统的静电能量（－25.86 kJ mol-1）高于目标蛋白-（R）-双氟甲基-复合物的静电能量（－18.21 kJ mol） -1）。一些关键的残基，如Lys-195，Lys-199，Ser-202和Trp-214，已显示出对手性双氯吡氟甲基的对映选择性毒性具有不同的重要性。显然，这种情况将为评估手性环境污染物对人体的潜在危害提供机械线索。
更新日期：2020-04-08
中文翻译：
估计手性双氯芬酸的潜在毒性：对映选择性行为的机理见解。
手性污染物在环境中分布广泛；但是，这些化学物质的对映选择性毒性作用尚未完全阐明。通过湿法实验和计算毒理学，该故事旨在探讨手性双氯氟酚-甲基与目标蛋白在对映体水平上的静态和动态毒性反应，并进一步揭示手性农药对映选择性毒性的微观机理。稳态和时间分辨结果表明，两种（R）-/（S）-对映异构体均可以与目标蛋白形成稳定的毒性缀合物，生物亲和力分别为1.156×104 M-1 / 1.734×104 M-1。反应中发生了明显的对映选择性。毒性作用模式的结果表明，位于IIA亚结构域的双氯氟甲基对映体 （S）-二氯氟甲基与残基之间重要的非共价相互作用的强度大于（R）-二氯氟甲基的残基。手性反应的吉布斯自由能分别为－26.89 / －29.40 kJ mol-1和－25.79 / －30.08 kJ mol-1，这与光化学和定点竞争分析的结果一致。动态对映选择性过程说明，内在蛋白质构象柔性对（R）-二氯氟甲基的毒性反应的影响低于（S）-二氯氟甲基的毒性反应，这是由于四个环的构型变化和空间位移引起的区域（即h6↔h7，h1↔h2，h5↔h6和h8↔h9）。圆二色性光谱的定量数据证实了这种结果。能量分解表明，目标蛋白-（S）-双氟甲基-系统的静电能量（－25.86 kJ mol-1）高于目标蛋白-（R）-双氟甲基-复合物的静电能量（－18.21 kJ mol） -1）。一些关键的残基，如Lys-195，Lys-199，Ser-202和Trp-214，已显示出对手性双氯吡氟甲基的对映选择性毒性具有不同的重要性。显然，这种情况将为评估手性环境污染物对人体的潜在危害提供机械线索。
京公网安备 11010802027423号