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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。半胱氨酸蛋白酶几乎存在于所有真核生物中，并在广泛的生物过程和疾病中发挥重要作用，包括抗原加工、细菌感染、关节炎、骨质疏松症、阿尔茨海默病和癌细胞侵袭。木瓜蛋白酶超家族的几种半胱氨酸蛋白酶对许多致病性原生动物的生命周期进程至关重要，因此它们代表了选择性抑制剂设计的潜在目标。人们还确定，人类对常见的室内尘螨过敏和哮喘反应需要这类酶的成员。高分辨率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是恰加斯病病原体克氏锥虫生命周期中的关键酶。本项目详细的研究将扩大我们对几种新的蛋白酶靶点的理解和调节能力，这些靶点显示在各种寄生虫感染以及尘螨过敏引起的哮喘的蛋白酶中。

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.