CYSTEINE PROTEASE-INHIBITOR COMPLEXES; DESIGNING THERAPEUTICS

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。 这项拟议工作的基础是在寄生虫病中蛋白分解作用的选择性控制领域提出和回答问题。我们的目标是了解蛋白水解酶的功能和调节，并使用结构生物学来指导有效的、特定的抑制剂的设计。为了实现这一点，我们使用了生化和结构生物学技术？包括高分辨率X射线结晶学。正在研究的目标包括那些与设计小分子抑制剂的目标相关的药物，以优化寄生虫感染的新疗法，这些药物来自以下生物体：来自克氏锥虫的Cruzain和Cruziain 2，来自布氏锥虫的TbCatB，来自恶性疟原虫的Fulciain 3，来自组织溶解Entomeba的EhCP4和来自蓝氏贾第鞭毛虫的GlCP。由这些病原体引起的疾病分别是查加斯？疾病、人类非洲锥虫病、疟疾、阿米巴结肠炎和贾第鞭毛虫病。

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. The basis of the proposed work is to ask and answer questions in the arena of selective control of proteolytic action in parasitic disease. Our goal is to understand the function and regulation of proteolytic enzymes and to use structural biology to guide the design of potent, specific inhibitors. To achieve this, we use biochemical and structural biology technologies ? including high resolution x-ray crystallography. Targets under study include those pertinent to the goal of designing small molecule inhibitors to be optimized to new therapeutics for parasitic infection and are derived from the following organisms: cruzain and cruzipain 2, from Trypanosoma cruzi, TbCatB from Trypanosoma brucei rhodesiense, falcipain 3 from Plasmodium falciparum, EhCP4 from Entomeba histolytica and GlCP from Giardia lamblia. The diseases caused by these agents are, respectively, Chagas? disease, Human African Trypanosomiasis, malaria, amoebic colitis and giardiasis.