BIOLOGICAL ROLES OF PLASMEPSINS

疟疾是世界上最具破坏性的疾病之一。药效 抗药性正在迅速使我们的抗疟疾药物过时。这个 拟议的研究项目的目标是在分子水平上理解和 最终抑制人类天冬氨酸蛋白酶的功能 疟疾寄生虫恶性疟原虫。寄生虫通过分解代谢而生长 宿主红细胞血红蛋白和利用由此产生的氨基酸作为蛋白质 综合。PI已经表明，天冬氨酸蛋白酶的作用可以解开 通过战略性切割血红蛋白分子，进一步暴露，有效 蛋白质分解。阻断血红蛋白降解的天冬氨酸蛋白酶抑制剂 杀灭培养中的恶性疟原虫。一个天冬氨酸蛋白酶基因家族 存在于恶性疟原虫基因组数据库中。私隐专员建议审查 表达，定位，生物合成，酶学，底物特异性和 编码的天冬氨酸蛋白酶的功能。目标是更好地理解 天冬氨酸蛋白酶在寄生虫生物学和血红蛋白中的作用 特别是降解，着眼于未来的药物开发。

Malaria is one of the world's most devastating diseases. Drug resistance is rapidly rendering our antimalarial armamentarium obsolete. The goal of the proposed research project is to understand at a molecular level and ultimately to inhibit the function of the aspartic proteases of the human malaria parasite, Plasmodium falciparum. The parasite grows by catabolizing host erythrocyte hemoglobin and using the resulting amino acids for protein synthesis. The PI has shown that aspartic protease action unravels the hemoglobin molecule by strategic cleavage, exposing for further, efficient proteolysis. Aspartic protease inhibitors that block hemoglobin degradation kill P. falciparum parasites in culture. A family of aspartic protease genes exists in the falciparum genomic database. The PI proposes to examine the expression, location, biosynthesis, enzymology, substrate specificity and function of the encoded aspartic proteases. The goal is to better understand the roles of aspartic proteases in parasite biology generally and in hemoglobin degradation specifically, with an eye toward future drug development.