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首页> 美国卫生研究院文献>Scientific Reports >Structural and functional characterization of suramin-bound MjTX-I from Bothrops moojeni suggests a particular myotoxic mechanism
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Structural and functional characterization of suramin-bound MjTX-I from Bothrops moojeni suggests a particular myotoxic mechanism

机译：来自Bothrops moojeni的与苏拉明结合的MjTX-I的结构和功能表征表明特定的肌毒性机制

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Local myonecrosis is the main event resulting from snakebite envenomation by the Bothrops genus and, frequently, it is not efficiently neutralized by antivenom administration. Proteases, phospholipases A2 (PLA2) and PLA2-like toxins are found in venom related to muscle damage. Functional sites responsible for PLA2-like toxins activity have been proposed recently; they consist of a membrane docking-site and a membrane rupture-site. Herein, a combination of functional, biophysical and crystallographic techniques was used to characterize the interaction between suramin and MjTX-I (a PLA2-like toxin from Bothrops moojeni venom). Functional in vitro neuromuscular assays were performed to study the biological effects of the protein-ligand interaction, demonstrating that suramin neutralizes the myotoxic effect of MjTX-I. Calorimetric assays showed two different binding events: (i) inhibitor-protein interactions and (ii) toxin oligomerization processes. These hypotheses were also corroborated with dynamic light and small angle X-ray scattering assays. The crystal structure of the MjTX-I/suramin showed a totally different interaction mode compared to other PLA2-like/suramin complexes. Thus, we suggested a novel myotoxic mechanism for MjTX-I that may be inhibited by suramin. These results can further contribute to the search for inhibitors that will efficiently counteract local myonecrosis in order to be used as an adjuvant of conventional serum therapy.
机译：局部肌坏死是Bothrops属蛇毒咬伤所致的主要事件，通常，抗蛇毒血清不能有效地中和。在与肌肉损伤有关的毒液中发现了蛋白酶，磷脂酶A2（PLA2）和类似PLA2的毒素。最近已经提出了负责PLA2样毒素活性的功能位点。它们由一个膜对接点和一个膜破裂点组成。在这里，功能，生物物理和晶体学技术的组合被用来表征苏拉明和MjTX-1（Bothrops moojeni毒液的PLA2样毒素）之间的相互作用。进行功能性体外神经肌肉测定以研究蛋白质-配体相互作用的生物学效应，证明苏拉明中和了MjTX-1的肌毒性作用。量热分析显示了两种不同的结合事件：（i）抑制剂-蛋白质相互作用和（ii）毒素寡聚过程。这些假设也得到了动态光和小角度X射线散射测定的证实。与其他PLA2-like /苏拉明复合物相比，MjTX-1 /苏拉明的晶体结构显示出完全不同的相互作用模式。因此，我们提出了可能被苏拉明抑制的一种新型的MjTX-I肌毒性机制。这些结果可进一步有助于寻找可有效抵消局部肌坏死的抑制剂，以用作常规血清疗法的佐剂。

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