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恶性疟原虫组织天冬氨酸蛋白酶原(proHAP)蛋白肽特异性结合红细胞并在体外抑制入侵过程。

P. falciparum pro-histoaspartic protease (proHAP) protein peptides bind specifically to erythrocytes and inhibit the invasion process in vitro.

作者信息

Valbuena John, Vera Ricardo, Puentes Alvaro, Ocampo Marisol, Garcia Javier, Curtidor Hernando, Lopez Ramses, Rodriguez Luis, Rosas Jaiver, Cortes Jimena, Forero Martha, Pinto Martha, Patarroyo Manuel Elkin

机构信息

Fundacion Instituto de Inmunologia de Colombia (FIDIC), Cra 50 26-00, Bogotá, Colombia.

出版信息

Biol Chem. 2005 Apr;386(4):361-7. doi: 10.1515/BC.2005.043.

DOI:10.1515/BC.2005.043
PMID:15899698
Abstract

Plasmodium falciparum histoaspartic protease (HAP) is an active enzyme involved in haemoglobin degradation. HAP is expressed as an inactive 51-kDa zymogen and is cleaved into an active 37-kDa enzyme. It has been proposed that this kind of protease might be implicated in the parasite's invasion of erythrocytes; however, this protein's role during invasion has still to be determined. Synthetic peptides derived from the HAP precursor (proHAP) were tested in erythrocyte binding assays to identify their possible function in the invasion process. Two proHAP high-activity binding peptides (HABPs) specifically bound to erythrocytes; these peptides were numbered 30609 (101LKNYIKESVKLFNKGLTKKS120) and 30610 (121YLGSEFDNVELKDLANVLSF140 ). The binding of these two peptides was saturable, presenting nanomolar affinity constants. These peptides interacted with 26- and 45-kDa proteins on the erythrocyte surface; the nature of these receptor sites was studied in peptide binding assays using enzyme-treated erythrocytes. The HABPs showed greater than 90% merozoite invasion inhibition in in vitro assays. Goat serum containing proHAP polymeric peptide antibodies inhibited parasite invasion in vitro .

摘要

恶性疟原虫组织天冬氨酸蛋白酶(HAP)是一种参与血红蛋白降解的活性酶。HAP以无活性的51 kDa酶原形式表达,并被切割成有活性的37 kDa酶。有人提出这种蛋白酶可能与疟原虫侵入红细胞有关;然而,这种蛋白质在侵入过程中的作用仍有待确定。在红细胞结合试验中测试了源自HAP前体(proHAP)的合成肽,以确定它们在侵入过程中的可能功能。两种proHAP高活性结合肽(HABP)特异性结合红细胞;这些肽分别编号为30609(101LKNYIKESVKLFNKGLTKKS120)和30610(121YLGSEFDNVELKDLANVLSF140)。这两种肽的结合是可饱和的,呈现出纳摩尔亲和力常数。这些肽与红细胞表面的26 kDa和45 kDa蛋白质相互作用;在使用酶处理红细胞的肽结合试验中研究了这些受体位点的性质。在体外试验中,HABP显示出大于90%的裂殖子侵入抑制作用。含有proHAP聚合肽抗体的山羊血清在体外抑制寄生虫侵入。

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