首页> 外国专利> CRYSTAL STRUCTURE OF THE HUMAN G267S CALPAIN-5 PROTEASE CORE DOMAIN AND ITS USE IN RATIONAL DRUG DESIGN FOR IDENTIFYING INHIBITORS OF CALPAIN-5

CRYSTAL STRUCTURE OF THE HUMAN G267S CALPAIN-5 PROTEASE CORE DOMAIN AND ITS USE IN RATIONAL DRUG DESIGN FOR IDENTIFYING INHIBITORS OF CALPAIN-5

机译:人G267S钙蛋白酶核心结构域的晶体结构及其在合理药物设计中的应用

摘要

A high-resolution crystallographic structure of the mutant human G267S calpain-5 protease core domain at 2.22 Å resolution and methods of crystallizing the mutant human G267S calpain-5 protease core domain are provided. In addition, a computer readable medium comprising atomic coordinates of the x-ray crystallographic structure of the mutant human G267S calpain-5 protease core domain and a computer system comprising atomic coordinates of the x-ray crystallographic structure of the mutant human G267S calpain-5 protease core domain stored in memory are also provided. The G267S mutation is associated with hyperactivity of calpain-5 and is linked to the inherited disease, neovascular inflammatory vitreoretinopathy. Methods of using the crystallographic structure in rational design of small molecule drugs that inhibit calpain-5 for treatment of retinal diseases such as neovascular inflammatory vitreoretinopathy and other diseases associated with calpain-5 hyperactivity are also provided.
机译:本发明提供了2.22Å分辨率的突变人类G267S钙蛋白酶核心结构域的高分辨率晶体结构和结晶突变人类G267S钙蛋白酶核心结构域的方法。此外,还提供了一种计算机可读介质,其包括存储在存储器中的突变人类G267S钙蛋白酶核心域的x射线晶体结构的原子坐标,以及一种计算机系统,其包括存储在存储器中的突变人类G267S钙蛋白酶核心域的x射线晶体结构的原子坐标。G267S突变与钙蛋白酶-5的过度活跃有关,并与遗传性疾病、新生血管炎性玻璃体视网膜病变有关。本发明还提供了在合理设计抑制钙蛋白酶-5的小分子药物中使用晶体结构的方法,该小分子药物用于治疗视网膜疾病,例如新生血管炎性玻璃体视网膜病变和与钙蛋白酶-5多动相关的其他疾病。

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