Xu Xiaoxiao, Xu Qingliang, Chen Fangling, Shi Juan, Liu Yuntian, Chu Yanyan, Wan Shengbiao, Jiang Tao, Yu Rilei
Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China Qingdao 266003 China
Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology Qingdao 266003 China.
RSC Adv. 2019 Jan 3;9(2):668-674. doi: 10.1039/c8ra06103c. eCollection 2019 Jan 2.
μ-Conotoxin PIIIA, a peptide toxin isolated from , blocks the skeletal muscle voltage-gated sodium channel Na1.4 with significant potency. PIIIA has three disulfide bonds, which contribute largely to its highly constrained and stable structure. In this study, a combination of experimental studies and computational modeling were performed to assess the effects of deletion of the disulfide bonds on the structure and activity of PIIIA. The final results indicate that the three disulfide bonds of PIIIA are required to produce the effective inhibition of Na1.4, and the removal of any one of the disulfide bonds significantly reduces its binding affinity owing to secondary structure variation, among which the Cys11-Cys22 is the most important for sustaining the structure and activity of PIIIA.
μ-芋螺毒素PIIIA是一种从[来源未提及]分离出的肽毒素，它能高效阻断骨骼肌电压门控钠通道Na1.4。PIIIA有三个二硫键，这在很大程度上促成了其高度受限且稳定的结构。在本研究中，结合实验研究与计算建模来评估二硫键缺失对PIIIA结构和活性的影响。最终结果表明，PIIIA的三个二硫键是产生对Na1.4有效抑制所必需的，去除任何一个二硫键都会因二级结构变化而显著降低其结合亲和力，其中Cys11-Cys22对维持PIIIA的结构和活性最为重要。
