Gamboa de Domínguez N D, Rosenthal P J
Department of Medicine, San Francisco General Hospital, University of California, San Francisco, USA.
Blood. 1996 May 15;87(10):4448-54.
Erythrocytic malaria parasites degrade hemoglobin as a source of amino acids for parasite protein synthesis. Cysteine proteinase inhibitors have been shown to block the hydrolysis of globin by cultured parasites, indicating that a malarial cysteine proteinase is required for this process. In the present study, we have evaluated the role of parasite proteinases in earlier steps of hemoglobin degradation, namely the disassociation of the hemoglobin tetramer and the separation of heme from globin. Hemoglobin did not spontaneously denature or release heme under the pH and reducing conditions of the malarial food vacuole, suggesting that parasite enzymatic activity is necessary for early steps in hemoglobin degradation. The incubation of cultured parasites with cysteine proteinase inhibitors inhibited the denaturation of hemoglobin and the release of heme from globin. These results suggest that, in addition to its role in globin hydrolysis, a malarial cysteine proteinase participates in the dissociation of the hemoglobin tetramer and the release of heme from globin. Thus, the malarial cysteine proteinase is a promising target for antimalarial chemotherapy.
红细胞疟原虫降解血红蛋白，将其作为寄生虫蛋白质合成所需氨基酸的来源。半胱氨酸蛋白酶抑制剂已被证明可阻断培养的寄生虫对珠蛋白的水解，这表明该过程需要一种疟原虫半胱氨酸蛋白酶。在本研究中，我们评估了寄生虫蛋白酶在血红蛋白降解早期步骤中的作用，即血红蛋白四聚体的解离以及血红素与珠蛋白的分离。在疟原虫食物泡的pH值和还原条件下，血红蛋白不会自发变性或释放血红素，这表明寄生虫的酶活性对于血红蛋白降解的早期步骤是必需的。用半胱氨酸蛋白酶抑制剂培养寄生虫可抑制血红蛋白的变性以及血红素从珠蛋白中的释放。这些结果表明，除了在珠蛋白水解中的作用外，疟原虫半胱氨酸蛋白酶还参与血红蛋白四聚体的解离以及血红素从珠蛋白中的释放。因此，疟原虫半胱氨酸蛋白酶是抗疟化疗的一个有前景的靶点。
