polysialyltransferase domain

  • 文章类型: Journal Article
    神经元细胞粘附分子(NCAM)上的聚唾液酸(polySia)的表达称为NCAM-聚唾液酸化,这与肿瘤细胞的迁移和侵袭以及侵袭性临床状态密切相关。因此,在临床治疗中,选择合适的药物来阻断肿瘤细胞的迁移是非常重要的。在这项研究中,我们提出,与CMP和低分子量肝素(LMWH)相比,乳铁蛋白(LFcinB11)可能是抑制NCAM聚唾液酸化的更好候选物,这是根据我们的核磁共振研究确定的。此外,中性粒细胞胞外陷阱(NETs)代表了细胞死亡过程中最戏剧性的阶段,NETs的释放与自身免疫性疾病和炎症性疾病的发病机制有关,被提议参与肾小球肾炎,慢性肺病,脓毒症,和血管疾病。在这项研究中,还确定了使用LFcinB11作为抑制剂抑制NET释放的分子机制。基于这些结果,LFcinB11被认为是抑制NCAM聚唾液酸化和NETs释放的双功能抑制剂。
    The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. Thus, it is important to select a proper drug to block tumor cell migration during clinical treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a better candidate for inhibiting NCAM polysialylation when compared with CMP and low-molecular-weight heparin (LMWH), which were determined based on our NMR studies. Furthermore, neutrophil extracellular traps (NETs) represent the most dramatic stage in the cell death process, and the release of NETs is related to the pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. In this study, the molecular mechanisms involved in the inhibition of NET release using LFcinB11 as an inhibitor were also determined. Based on these results, LFcinB11 is proposed as being a bifunctional inhibitor for inhibiting both NCAM polysialylation and the release of NETs.
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  • 文章类型: Journal Article
    多唾液酸(polySia)在神经细胞粘附分子(NCAM)上的过表达促进高唾液酸化,从而有利于癌细胞的迁移和侵袭。已经提出需要抑制聚唾液酸转移酶结构域(PSTD)和CMP-Sia之间的结合以阻断高唾液酸化的作用。在这项研究中,基于分子之间的相互作用特征,在CMP-Sia和triSia(寡唾液酸三聚体)存在下,CMP被证实是聚唾液酸转移酶(polyST)的竞争性抑制剂。进一步的NMR分析表明,当CMP-Sia和polySia在溶液中共存时,聚唾液酸化可以部分抑制。此外,一个意想不到的发现是,CMP-Sia在减少PSTD上polysia链的聚集程度方面发挥了作用,并且可能对多唾液酸化的抑制有益。这项研究的发现可能为癌症治疗药物和抑制剂的最佳设计提供新的见解。
    The overexpression of polysialic acid (polySia) on neural cell adhesion molecules (NCAM) promotes hypersialylation, and thus benefits cancer cell migration and invasion. It has been proposed that the binding between the polysialyltransferase domain (PSTD) and CMP-Sia needs to be inhibited in order to block the effects of hypersialylation. In this study, CMP was confirmed to be a competitive inhibitor of polysialyltransferases (polySTs) in the presence of CMP-Sia and triSia (oligosialic acid trimer) based on the interactional features between molecules. The further NMR analysis suggested that polysialylation could be partially inhibited when CMP-Sia and polySia co-exist in solution. In addition, an unexpecting finding is that CMP-Sia plays a role in reducing the gathering extent of polySia chains on the PSTD, and may benefit for the inhibition of polysialylation. The findings in this study may provide new insight into the optimal design of the drug and inhibitor for cancer treatment.
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