Lalmanach Gilles, Boulangé Alain, Serveau Carole, Lecaille Fabien, Scharfstein Julio, Gauthier Francis, Authié Edith
Laboratoire d'Enzymologie et Chimie des Protéines, INSERM EMI-U 00.10, Université François Rabelais, Faculté de Médecine, Tours, France.
Biol Chem. 2002 May;383(5):739-49. doi: 10.1515/BC.2002.077.
Trypanosomes are the etiological agents of human sleeping sickness and livestock trypanosomosis (nagana), which are major diseases in Africa. Their cysteine proteases (CPs), which are members of the papain family, are expressed during the infective stages of the parasites' life cycle. They are suspected to act as pathogenic factors in the mammalian host, where they also trigger prominent immune responses. Trypanosoma congolense, a major pathogenic species in livestock, possesses at least two families of closely related CPs, named CP1 and CP2. Congopain, a CP2-type of enzyme, shares structural and functional resemblances with cruzipain from T. cruzi and with mammalian cathepsin L. Like CPs from other Trypanosomatids, congopain might be an attractive target for trypanocidal drugs. Here we summarise the current knowledge in the two main areas of research on congopain: first, the biochemical properties of congopain were characterised and its substrate specificity was determined, as a first step towards drug design; second, the possibility was being explored that inhibition of congopain by host-specific antibodies may mitigate the pathology associated with trypanosome infection.
锥虫是人类昏睡病和家畜锥虫病(那加那病)的病原体,这两种疾病是非洲的主要疾病。它们的半胱氨酸蛋白酶(CPs)属于木瓜蛋白酶家族成员,在寄生虫生命周期的感染阶段表达。人们怀疑它们在哺乳动物宿主中作为致病因素起作用,在宿主中它们还引发显著的免疫反应。刚果锥虫是家畜中的一种主要致病物种,拥有至少两个密切相关的CP家族,分别命名为CP1和CP2。刚果锥蛋白酶是一种CP2型酶,与克氏锥虫的克氏锥蛋白酶以及哺乳动物组织蛋白酶L在结构和功能上相似。与其他锥虫的CPs一样,刚果锥蛋白酶可能是杀锥虫药物的一个有吸引力的靶点。在此,我们总结了关于刚果锥蛋白酶的两个主要研究领域的当前知识:第一,对刚果锥蛋白酶的生化特性进行了表征,并确定了其底物特异性,这是药物设计的第一步;第二,正在探索宿主特异性抗体对刚果锥蛋白酶的抑制作用是否可以减轻与锥虫感染相关的病理状况。