An inhibition model of BPTI to unlinked dengue virus NS2B‐NS3 protease
An inhibition model of BPTI to unlinked dengue virus NS2B‐NS3 protease
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DOI：
10.1016/j.febslet.2014.05.063
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发表时间：
2014-08
期刊：
影响因子：
3.5
通讯作者：
Hua Li;Lei Zhu;Shulin Hou;Jing Yang;Junfeng Wang;Jinsong Liu
中科院分区：
文献类型：
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作者：
Hua Li;Lei Zhu;Shulin Hou;Jing Yang;Junfeng Wang;Jinsong Liu
治疗登革病毒感染的一种方法是抑制其在病毒成熟中起重要作用的NS 2B-NS 3蛋白酶。然而，缺乏蛋白酶活性构象的结构信息阻碍了相关的药物设计。通过共表达系统，我们获得了未连接形式的活性双组分蛋白酶。BPTI对这种未连接的蛋白酶显示出强的竞争性抑制活性（Ki= 6.5 nM），该蛋白酶采用封闭构象。基于生物化学和核磁共振微扰信息，提出了BPTI对NS 2B-NS 3蛋白酶的抑制模型。
One approach to treating the dengue virus infection is to inhibit its NS2B-NS3 protease that plays a vital role in virus maturation. However, the lack of structural information on the active conformation of the protease hindered related drug design. With a co-expression system, we obtained the active two-component protease in its unlinked form. BPTI shows strong competitive inhibitory activity (Ki= 6.5 nM) against this unlinked protease, which adopts a closed conformation. Based on the biochemical and NMR perturbation information, an inhibition model of BPTI to NS2B-NS3 protease is proposed.