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首页> 外文期刊>RSC Advances >Role of the disulfide bond on the structure and activity of mu-conotoxin PIIIA in the inhibition of Na(V)1.4
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Role of the disulfide bond on the structure and activity of mu-conotoxin PIIIA in the inhibition of Na(V)1.4

机译：二硫键的作用对瘤（v）1.4的抑制mu-芋诺毒素Piiia的结构和活性

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摘要

mu -Conotoxin PIIIA, a peptide toxin isolated from Conus purpurascens, blocks the skeletal muscle voltage-gated sodium channel Na(V)1.4 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 Na(V)1.4, 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.
机译：Mu-Conotoxin Piiia，肽毒素中分离的肽毒素，阻断骨骼肌电压门控钠通道Na（v）1.4，具有显着效力。 PIIIa具有三种二硫键，这主要有助于其高度约束和稳定的结构。 在该研究中，进行了实验研究和计算建模的组合，以评估缺失二硫键对PIIIA结构和活性的影响。 最终结果表明，需要的三种PIIIa二硫键来产生Na（v）1.4的有效抑制，并且除了二次结构变异，除了二级结构变异，其中任何一种二硫键的除去明显降低其结合亲和力，其中包括Cys11 -Cys22对于维持PIIIA的结构和活性最为重要。

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  • 来源
    《RSC Advances》 |2019年第2期|共7页
  • 作者

    Xu Xiaoxiao; Xu Qingliang; Chen Fangling; Shi Juan; Liu Yuntian; Chu Yanyan; Wan Shengbiao; Jiang Tao; Yu Rilei;

  • 作者单位

    Ocean Univ China Sch Med &

    Pharm Chinese Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Ocean Univ China Sch Med &

    Pharm Chinese Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Ocean Univ China Sch Med &

    Pharm Chinese Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Ocean Univ China Sch Med &

    Pharm Chinese Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Ocean Univ China Sch Med &

    Pharm Chinese Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Qingdao Natl Lab Marine Sci &

    Technol Lab Marine Drugs &

    Bioprod Qingdao 266003 Peoples R China;

    Ocean Univ China Sch Med &

    Pharm Chinese Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Ocean Univ China Sch Med &

    Pharm Chinese Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

    Ocean Univ China Sch Med &

    Pharm Chinese Minist Educ Key Lab Marine Drugs Qingdao 266003 Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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