This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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