Departamento de Biofísica e Farmacologia, Instituto de Biociências, Universidade Estadual Paulista (UNESP), Botucatu, SP, Brazil.
Departamento de Biofísica e Farmacologia, Instituto de Biociências, Universidade Estadual Paulista (UNESP), Botucatu, SP, Brazil; UMR 7590, CNRS, Muséum National d'Histoire Naturelle, IRD, Institut de Minéralogie, Physique des Matériaux et de Cosmochimie (IMPMC), Sorbonne Université, Paris, France.
Biochimie. 2024 Mar;218:46-56. doi: 10.1016/j.biochi.2023.08.018. Epub 2023 Sep 1.
In accidents involving Crotalus snakes, the crotoxin complex (CTX) plays lethal action due to its neurotoxic activity. On the other hand, CTX have potential biotechnological application due to its anti-tumoral, anti-inflammatory, antimicrobial, analgesic and immunomodulatory properties. CTX is a heterodimer composed of Crotoxin A (CA or crotapotin), the acidic nontoxic and non-enzymatic component and; Crotoxin B (CB), a basic, toxic and catalytic PLA. Currently, there are two classes of CTX isoforms, whose differences in their biological activities have been attributed to features presented in CB isoforms. Here, we present the crystal structure of CB isolated from the Crotalus durissus collilineatus venom. It amino acid sequence was assigned using the SEQUENCE SLIDER software, which revealed that the crystal structure is a heterodimer composed of two new CB isoforms (colCB-A and colCB-B). Bioinformatic and biophysical analyses showed that the toxin forms a tetrameric assembly in solution similar to CB from Crotalus durissus terrificus venom, despite some differences observed at the dimeric interface. By the previously proposed classification, the colCB-B presents features of the class I isoforms while colCB-A cannot be classified into classes I and II based on its amino acid sequence. Due to similar features observed for other CB isoforms found in the NCBI database and the results obtained for colCB-A, we suggest that there are more than two classes of CTX and CB isoforms in crotalic venoms.
在涉及响尾蛇的事故中，由于其神经毒性作用，响尾蛇毒素复合物（CTX）发挥致命作用。另一方面，CTX 具有抗肿瘤、抗炎、抗菌、镇痛和免疫调节特性，因此具有潜在的生物技术应用价值。CTX 是由 Crotoxin A（CA 或 crotapotin）组成的异二聚体，CA 是酸性无毒非酶成分；Crotoxin B（CB）是碱性、有毒和催化 PLA。目前，有两种 CTX 同工型，其生物活性的差异归因于 CB 同工型中存在的特征。在这里，我们展示了来自 Crotalus durissus collilineatus 毒液的 CB 的晶体结构。使用 SEQUENCE SLIDER 软件对其氨基酸序列进行了分配，结果表明该晶体结构是由两个新的 CB 同工型（colCB-A 和 colCB-B）组成的异二聚体。生物信息学和生物物理分析表明，该毒素在溶液中形成类似于 Crotalus durissus terrificus 毒液中 CB 的四聚体组装，尽管在二聚体界面观察到一些差异。根据之前提出的分类，colCB-B 具有 I 类同工型的特征，而 colCB-A 不能根据其氨基酸序列归类为 I 类和 II 类。由于在 NCBI 数据库中发现的其他 CB 同工型具有相似的特征，并且 colCB-A 的结果也表明，在响尾蛇毒液中存在不止两类 CTX 和 CB 同工型。
