Chemistry Institute, University of Campinas UNICAMP, Campinas SP 13083-970, Brazil.
Parasitology. 2011 Sep;138(10):1245-58. doi: 10.1017/S0031182011001077. Epub 2011 Aug 8.
Sirtuin proteins form a family of NAD+-dependent protein deacetylases that are considered potential drug targets against parasites. Here, we present the first characterization of a sirtuin orthologue from Leishmania amazonensis, an aetiological agent of American tegumentary leishmaniasis that has been the subject of many studies focused in the development of therapeutic approaches. The protein has high sequence identity with other Kinetoplastid Silent information regulator 2 Related Protein 1 (Sir2RP1) and was named LaSir2RP1. The gene exists as a single copy, encoding a monomeric protein (LaSir2RP1) of approximately 41 kDa that has NAD+-dependent deacetylase activity. LaSir2RP1 was immunodetected in total protein extracts, in cytoplasmic granules, and in the secreted material of both promastigotes and lesion-derived amastigotes. Analysis of both lectin‑affinity purified promastigote and amastigote extracts revealed the presence of a major enriched protein of approximately 66 kDa that was recognized by an anti-LaSir2RP1 serum, suggesting that a parasite sirtuin could be glycosylated in vivo.
Sirtuin 蛋白构成了一个 NAD+依赖性蛋白去乙酰化酶家族，它们被认为是针对寄生虫的潜在药物靶点。在这里，我们首次描述了来自美洲利什曼原虫的 Sirtuin 同源物，该蛋白是美洲皮肤利什曼病的病原体，已经成为许多专注于治疗方法开发的研究的主题。该蛋白与其他 Kinetoplastid Silent information regulator 2 Related Protein 1 (Sir2RP1) 具有高度序列同一性，并被命名为 LaSir2RP1。该基因作为单个拷贝存在，编码一个单体蛋白（LaSir2RP1），约 41 kDa，具有 NAD+依赖性去乙酰化酶活性。LaSir2RP1 在总蛋白提取物、细胞质颗粒以及前鞭毛体和病变衍生的无鞭毛体的分泌物质中均被免疫检测到。对凝集素亲和纯化的前鞭毛体和无鞭毛体提取物的分析表明，存在一种约 66 kDa 的主要富集蛋白，该蛋白被抗 LaSir2RP1 血清识别，提示寄生虫 Sirtuin 可能在体内发生糖基化。
