肉毒梭菌
肉毒中毒
肉毒神经毒素
弛缓性麻痹
绑定域
神经肌肉接头
结合位点
生物
肽序列
生物化学
化学
毒素
遗传学
医学
麻痹
神经科学
基因
外科
作者
Kyle S. Gregory,K. Ravi Acharya
出处
期刊:Toxins
[Multidisciplinary Digital Publishing Institute]
日期:2023-01-18
卷期号:15 (2): 92-92
被引量:7
标识
DOI:10.3390/toxins15020092
摘要
Botulinum neurotoxins (BoNTs) cause flaccid neuromuscular paralysis by cleaving one of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex proteins. BoNTs display high affinity and specificity for neuromuscular junctions, making them one of the most potent neurotoxins known to date. There are seven serologically distinct BoNTs (serotypes BoNT/A to BoNT/G) which can be further divided into subtypes (e.g., BoNT/A1, BoNT/A2…) based on small changes in their amino acid sequence. Of these, BoNT/A1 and BoNT/B1 have been utilised to treat various diseases associated with spasticity and hypersecretion. There are potentially many more BoNT variants with differing toxicological profiles that may display other therapeutic benefits. This review is focused on the structural analysis of the cell-binding domain from BoNT/A1 to BoNT/A6 subtypes (HC/A1 to HC/A6), including features such as a ganglioside binding site (GBS), a dynamic loop, a synaptic vesicle glycoprotein 2 (SV2) binding site, a possible Lys–Cys/Cys–Cys bridge, and a hinge motion between the HCN and HCC subdomains. Characterising structural features across subtypes provides a better understanding of how the cell-binding domain functions and may aid the development of novel therapeutics.
科研通智能强力驱动
Strongly Powered by AbleSci AI