Cazzulo J J, Stoka V, Turk V
Instituto de Investigaciones Bioquímicas, Luis F. Leloir, Fundación Campomar - CONICET - Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Biol Chem. 1997 Jan;378(1):1-10. doi: 10.1515/bchm.1997.378.1.1.
Trypanosoma cruzi, the parasitic protozoan which causes the American Trypanosomiasis, Chagas disease, contains a major cysteine proteinase (CP), cruzipain. The enzyme belongs to the papain family, but contains, as other CPs from Trypanosomatids, an unusual C-terminal extension. This C-terminal domain contains a number of post-translational modifications and is responsible for the immunodominant antigenic character of cruzipain in natural human infections. In addition, this domain is probably the cause of most of the microheterogeneities found in natural cruzipain. Irreversible inhibitors of CPs are able to block the parasite's life cycle at the differentiation steps, suggesting an essential role for CPs for parasite survival, and opening up possibilities of developing new chemotherapeutic agents against Chagas disease based on specific cruzipain inhibitors.
克氏锥虫是一种导致美洲锥虫病(查加斯病)的寄生原生动物,它含有一种主要的半胱氨酸蛋白酶(CP)——克氏锥虫蛋白酶。该酶属于木瓜蛋白酶家族,但与来自锥虫的其他CP一样,含有一个不寻常的C末端延伸。这个C末端结构域包含许多翻译后修饰,并且是克氏锥虫蛋白酶在自然人类感染中具有免疫显性抗原特性的原因。此外,该结构域可能是天然克氏锥虫蛋白酶中发现的大多数微异质性的原因。CP的不可逆抑制剂能够在分化步骤阻断寄生虫的生命周期,这表明CP对寄生虫的生存起着至关重要的作用,并为基于特异性克氏锥虫蛋白酶抑制剂开发治疗查加斯病的新化疗药物开辟了可能性。