New strategy for the development of drugs to treat serpinopathies based on structural biology

由丝氨酸蛋白酶抑制剂聚合引起的丝氨酸蛋白酶抑制剂病包括痴呆和肝硬化。自2008年以来，治疗药物开发的目标分子已从天然蛋白质转变为折叠中间体。在这项研究中，我们发现了三个种子化合物的治疗serpinopathies的基础上获得的数据，通过映射的重折叠中间体的neuroserpin，分析的延伸和结构域交换机制的neuroserpin和卵白蛋白的聚合物，和切割形式的致病突变体Ser49Pro的neuroserpin的晶体结构。

The serpinopathies resulting from serpin polymerization include dementia and cirrhosis. Since 2008, the target molecule for the development of the therapeutic agents has changed from the native protein to folding intermediates. In this study, we found three seed compounds for a cure of serpinopathies based on the data obtained by mapping of a refolding intermediate of neuroserpin, analysis of elongation and domain-swapping mechanisms of polymers of neuroserpin and ovalbumin, and a crystal structure of the cleaved form of the pathogenic mutant Ser49Pro of neuroserpin.