A role for the protease falcipain 1 in host cell invasion by the human malaria parasite
A role for the protease falcipain 1 in host cell invasion by the human malaria parasite
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DOI：
10.1126/science.1077426
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发表时间：
2002-12-06
期刊：
影响因子：
56.9
通讯作者：
Bogyo, M
中科院分区：
文献类型：
--
作者：
Greenbaum, DC;Baruch, A;Bogyo, M
恶性疟原虫的半胱氨酸蛋白酶是疟原虫生存所必需的，但其具体的细胞功能仍不清楚。我们使用带有小分子探针的化学蛋白质组筛选来表征整个寄生虫生命周期中的主要半胱氨酸蛋白酶。只有一种蛋白酶，falcipain 1，在侵入裂殖子阶段具有活性。通过筛选化学文库鉴定出的 Falcipain 1 特异性抑制剂可以阻止寄生虫入侵宿主红细胞，但对血红蛋白降解等正常寄生虫过程没有影响。这些结果证明了 falcipain 1 在宿主细胞侵袭中的特定作用，并为抗疟治疗建立了潜在的新靶标。
Cysteine proteases of Plasmodium falciparum are required for survival of the malaria parasite, yet their specific cellular functions remain unclear. We used a chemical proteomic screen with a small-molecule probe to characterize the predominant cysteine proteases throughout the parasite life cycle. Only one protease, falcipain 1, was active during the invasive merozoite stage. Falcipain 1-specific inhibitors, identified by screening of chemical libraries, blocked parasite invasion of host erythrocytes, yet had no effect on normal parasite processes such as hemoglobin degradation. These results demonstrate a specific role for falcipain 1 in host cell invasion and establish a potential new target for antimalarial therapeutics.