STRUCTURE-FUNCTION STUDIES OF CYSTEINE PROTEASES OF PARASITIC DISEASE AND ALLERG

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 半胱氨酸蛋白酶存在于几乎所有真核生物中，在抗原加工、细菌感染、关节炎、骨质疏松症、阿尔茨海默病、S病和癌细胞侵袭等广泛的生物学过程和疾病中发挥重要作用。木瓜蛋白酶超家族的几种半胱氨酸蛋白酶对许多致病原虫的生命周期进程至关重要，因此它们是选择性抑制剂设计的潜在靶点。也已经确定，人类对常见的屋尘螨的过敏和哮喘反应需要这种相同类别的酶。高分辨率的结构研究为设计选择性调节半胱氨酸蛋白酶CRUZAIN的抗寄生虫疗法提供了有价值的信息，CRUZAIN是查格斯病的病原体T.CRUZI生命周期中的关键酶。本计划中详细介绍的研究将扩大我们对多种寄生虫感染中所示的几种新的蛋白水解酶靶点以及尘螨过敏引起的哮喘的蛋白水解酶的了解和调控的能力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cysteine proteases are present in nearly all groups of eukaryotes and play vital roles in a wide range of biological processes and diseases, including antigen processing, bacterial infection, arthritis, osteoporosis, Alzheimer¿s disease and cancer cell invasion. Several cysteine proteases of the papain superfamily are critical to the life-cycle progression of many pathogenic protozoa and therefore they represent potential targets for selective inhibitor design. It has also been determined that members of this same class of enzyme are required for human allergic and asthmatic response to the common house dust mite. High-resolution structural studies have provided valuable information for the design of anti-parasitic therapeutics that selectively regulate the cysteine protease cruzain, a key enzyme in the lifecycle of T. cruzi, the causative agent of Chagas¿ disease. The studies detailed in this program will expand our understanding and ability to regulate several new protease targets indicated in a variety of parasitic infections as well as proteases of dust mite allergy induced asthma.