Department of Chemistry, Federal University of Lavras, P.O. Box 3037, 37200-000 Lavras, MG, Brazil.
Biomedical Research Center, University Hospital Hradec Kralove, 500 05 Hradec Kralove, Czech Republic.
Toxins (Basel). 2017 Oct 25;9(11):341. doi: 10.3390/toxins9110341.
Human phospholipase A₂ (PLA₂) of the IIA group (HGIIA) catalyzes the hydrolysis of membrane phospholipids, producing arachidonic acid and originating potent inflammatory mediators. Therefore, molecules that can inhibit this enzyme are a source of potential anti-inflammatory drugs, with different action mechanisms of known anti-inflammatory agents. For the study and development of new anti-inflammatory drugs with this action mechanism, snake venom PLA₂ (PLA₂) can be employed, since the PLA₂ has high similarity with the human PLA₂ HGIIA. Despite the high similarity between these secretory PLA₂s it is still not clear if these toxins can really be employed as an experimental model to predict the interactions that occur with the human PLA₂ HGIIA and its inhibitors. Thus, the present study aims to compare and evaluate, by means of theoretical calculations, docking and molecular dynamics simulations, as well as experimental studies, the interactions of human PLA₂ HGIIA and two PLA₂s toxin II and Crotoxin B (BthTX-II and CB, respectively). Our theoretical findings corroborate experimental data and point out that the human PLA₂ HGIIA and PLA₂ BthTX-II lead to similar interactions with the studied compounds. From our results, the PLA₂ BthTX-II can be used as an experimental model for the development of anti-inflammatory drugs for therapy in humans.
人 IIA 组磷脂酶 A₂（PLA₂）（HGIIA）催化膜磷脂水解，产生花生四烯酸并产生有效的炎症介质。因此，能够抑制这种酶的分子是潜在抗炎药物的来源，具有已知抗炎剂不同的作用机制。为了研究和开发具有这种作用机制的新型抗炎药物，可以使用蛇毒 PLA₂（PLA₂），因为 PLA₂与人 PLA₂ HGIIA 具有高度相似性。尽管这些分泌型 PLA₂之间具有高度相似性，但仍不清楚这些毒素是否真的可以用作实验模型来预测与人类 PLA₂ HGIIA 及其抑制剂的相互作用。因此，本研究旨在通过理论计算、对接和分子动力学模拟以及实验研究来比较和评估人 PLA₂ HGIIA 和两种 PLA₂毒素 II 和 Crotoxin B（BthTX-II 和 CB）之间的相互作用。我们的理论发现与实验数据相符，并指出人 PLA₂ HGIIA 和 PLA₂ BthTX-II 与所研究的化合物产生相似的相互作用。根据我们的结果，PLA₂ BthTX-II 可用作开发用于人类治疗的抗炎药物的实验模型。
