Laboratory of Molecular Modeling, Chemistry Department, Federal University of Lavras, 37200-000 Lavras, MG, Brazil.
Department of Health Sciences, Federal University of Espírito Santo, 29932-540 São Mateus, ES, Brazil.
Int J Mol Sci. 2018 Apr 23;19(4):1257. doi: 10.3390/ijms19041257.
Organophosphorus compounds (OP) are part of a group of compounds that may be hazardous to health. They are called neurotoxic agents because of their action on the nervous system, inhibiting the acetylcholinesterase (AChE) enzyme and resulting in a cholinergic crisis. Their high toxicity and rapid action lead to irreversible damage to the nervous system, drawing attention to developing new treatment methods. The diisopropyl fluorophosphatase (DFPase) enzyme has been considered as a potent biocatalyst for the hydrolysis of toxic OP and has potential for bioremediation of this kind of intoxication. In order to investigate the degradation process of the nerve agents Tabun, Cyclosarin and Soman through the wild-type DFPase, and taking into account their stereochemistry, theoretical studies were carried out. The intermolecular interaction energy and other parameters obtained from the molecular docking calculations were used to construct a data matrix, which were posteriorly treated by statistical analyzes of chemometrics, using the PCA (Principal Components Analysis) multivariate analysis. The analyzed parameters seem to be quite important for the reaction mechanisms simulation (QM/MM). Our findings showed that the wild-type DFPase enzyme is stereoselective in hydrolysis, showing promising results for the catalytic degradation of the neurotoxic agents under study, with the degradation mechanism performed through two proposed pathways.
有机磷化合物 (OP) 属于一组可能对健康有害的化合物。由于其对神经系统的作用，它们被称为神经毒剂，抑制乙酰胆碱酯酶 (AChE) 酶，导致胆碱能危机。它们的高毒性和快速作用导致神经系统的不可逆转损伤，引起人们对开发新的治疗方法的关注。二异丙基氟膦酸酶 (DFPase) 酶已被认为是水解有毒 OP 的有效生物催化剂，具有这种中毒生物修复的潜力。为了研究野生型 DFPase 对塔崩、沙林和梭曼神经毒剂的降解过程，并考虑到它们的立体化学，进行了理论研究。从分子对接计算中获得的分子间相互作用能和其他参数用于构建数据矩阵，然后通过化学计量学的主成分分析 (PCA) 多元分析对其进行统计分析处理。分析得到的参数对于反应机制模拟 (QM/MM) 似乎非常重要。我们的研究结果表明，野生型 DFPase 酶在水解过程中具有立体选择性，对所研究的神经毒剂的催化降解表现出良好的效果，其降解机制通过两种提出的途径进行。
