...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Molecular Basis of Activation of Endopeptidase Activity of Botulinum Neurotoxin Type E
【24h】

Molecular Basis of Activation of Endopeptidase Activity of Botulinum Neurotoxin Type E

机译：E型肉毒杆菌神经毒素激活内肽酶活性的分子基础

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Botulinum neurotoxins (BoNTs) are a group of large proteins that are responsible for the clinicalnsyndrome of botulism. The seven immunologically distinct serotypes of BoNTs (A-G), each produced bynvarious strains of Clostridium botulinum, act on the neuromuscular junction by blocking the release of thenneurotransmitter acetylcholine, thereby resulting in flaccid muscle paralysis. BoNTs are synthesized as singleninactive polypeptide chains that are cleaved by endogenous or exogenous proteases to generate the activendichain form of the toxin. Nicking of the single chain BoNT/E to the dichain form is associated with 100-foldnincrease in toxicity. Here we investigated the activation mechanism of botulinum neurotoxin type E uponnnicking and subsequent reduction of disulfide bond. It was observed that nicking of BoNT/E significantlynenhances its endopeptidase activity and that at the physiological temperature of 37 u0001C the reduced form ofnnicked BoNT/E adopts a dynamically flexible conformation resulting from the exposure of hydrophobicnsegments and facilitating optimal cleavage of its substrate SNAP-25. Such reduction-induced increase in thenflexibility of the polypeptide folding provides a rationale for the mechanism of BoNT/E endopeptidasenagainst its intracellular substrate, SNAP-25, and complements current understanding of the mechanistics ofninteraction between the substrate and BoNT endopeptidase.
机译：肉毒杆菌神经毒素（BoNT）是一组导致肉毒中毒临床综合征的大蛋白。 BoNT的七种免疫学血清型（A-G），分别由不同的肉毒梭菌菌株产生，通过阻断神经递质乙酰胆碱的释放而作用于神经肌肉接头，从而导致松弛的肌肉麻痹。 BoNTs合成为单能活性多肽链，可被内源或外源蛋白酶切割以产生毒素的活性二链形式。单链BoNT / E形成双链的切口与毒性增加100倍有关。在这里，我们调查了切口和随后减少的二硫键后，E型肉毒神经毒素的激活机制。观察到BoNT / E的切口显着增强了其内肽酶的活性，并且在37 u0001C的生理温度下，缩合形式的BoNT / E的缩合形式由于暴露于疏水性链段并促进其底物SNAP-25的最佳裂解而具有动态柔性构象。 。多肽折叠的柔性的这种减少诱导的增加提供了BoNT / E内肽酶抗其细胞内底物SNAP-25的机理的原理，并补充了对底物与BoNT内肽酶之间相互作用机理的当前理解。

著录项

  • 来源
    《Biochemistry》 |2010年第11期|p.2510-2519|共10页
  • 作者

    Roshan V. Kukreja Shashi K. Sharma and Bal Ram Singh;

  • 作者单位

    ‡Botulinum Research Center and Department of Chemistry and Biochemistry, University of Massachusetts Dartmouth,285 Old Westport Road, North Dartmouth, Massachusetts 02747, and §FDA, Center for Food Safety and Applied Nutrition,5100 Paint Branch Parkway, HFS-712, College Park, Maryland 20740;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号