【摘要】 烟碱型乙酰胆碱受体(n AChRs)是配体门控离子通道,它与疼痛、阿尔茨海默氏病、成瘾等疾病密切相关。α-芋螺毒素是n AChRs的拮抗剂,也是治疗上述疾病的先导药物。乙酰胆碱结合蛋白(ACh BPs)与n AChRs的配体结合结构域同源性较高,它们的药理特性和离子通道激活机制也相类似,α-芋螺毒素与ACh BPs共结晶结构解析了α-芋螺毒素残基如何选择结合n AChRs。现对α-芋螺毒素与ACh BPs共结晶结构进行综述,旨在剖析α-芋螺毒素与n AChRs相互作用的关键残基,为开发药效更好的芋螺毒素提供参考依据。更多还原

【Abstract】 The nicotinic acetylcholine receptors( n AChRs) are ligand-gated ion-channel proteins. They are the drug targets for against pain,Alzheimer’ s disease and nicotine addiction etc. The α-conotoxins are the n AChRs inhibitors and the leading drugs. Acetylcholine-binding proteins( ACh BPs) are homologous to the ligand-binding domains of the n AChRs. The ACh BPs have similar characteristics and activation mechanisms of n AChRs. The crystal structures of α-conotoxins in complex with ACh BPs can provide the insights into the key residues which select for binding to n AChRs,and help design the potentα-conotoxin analogs as drug leads. This article has given an overview of the co-crystal structures of α-conotoxins in complex with ACh BPs,and the key residues for the selectivity of α-conotoxins for n AChRs,which will be valuable to design the new α-conotoxin-based drugs for treatment.更多还原