Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
Universidade Federal do Ceará, Fortaleza, Ceará, Brazil.
Int J Biol Macromol. 2018 Jan;106:369-378. doi: 10.1016/j.ijbiomac.2017.08.023. Epub 2017 Aug 10.
CaBo is a mannose/glucose-specific lectin purified from seeds of Canavalia bonariensis. In the present work, we report the CaBo crystal structure determined to atomic resolution in the presence of X-man, a specific ligand. Similar to the structural characteristics of other legume lectins, CaBo presented the jellyroll motif, a metal binding site occupied by calcium and manganese ions close to the carbohydrate-recognition domain (CRD). In vitro test of CaBo cytotoxicity against glioma cells demonstrated its ability to decrease the cellular viability and migration by induction of autophagy and cell death. Molecular docking simulations corroborate previous data indicating that the lectin's biological activities occur mostly through interactions with glycoproteins since the lectin interacted favorably with several N-glycans, especially those of the high-mannose type. Together, these results suggest that CaBo interacts with glycosylated cell targets and elicits a remarkable antiglioma activity.
CaBo 是从 Canavalia bonariensis 种子中纯化得到的甘露糖/葡萄糖特异性凝集素。在本工作中，我们报道了 CaBo 晶体结构，该结构在 X-man（一种特异性配体）存在的情况下解析至原子分辨率。与其他豆科凝集素的结构特征相似，CaBo 呈现出卷曲螺旋结构，金属结合位点由接近碳水化合物识别结构域（CRD）的钙离子和锰离子占据。体外实验表明，CaBo 对神经胶质瘤细胞的细胞毒性能够通过诱导自噬和细胞死亡来降低细胞活力和迁移。分子对接模拟实验证实了之前的数据，表明凝集素的生物活性主要通过与糖蛋白的相互作用发生，因为凝集素与多种 N-聚糖（尤其是高甘露糖型）有利地相互作用。综上所述，这些结果表明 CaBo 与糖基化的细胞靶标相互作用，并表现出显著的抗神经胶质瘤活性。
