Department of Biology, Indian Institute of Science Education and Research (IISER), Pune, India
Biosci Rep. 2019 Jun 20;39(6). doi: 10.1042/BSR20191369. Print 2019 Jun 28.
An explosion of sequence information in the genomics era has thrown up thousands of protein sequences without functional assignment. Though our ability to predict function based on sequence alone is improving steadily, we still have a long way to go. Proteins with common evolutionary origins carry telling sequence signatures, which ought to reveal their biological roles. These sequence signatures have allowed us to classify proteins into families with similar structures, and possibly, functions. Yet, evolution is a perpetual tinkerer, and hence, sequence signatures alone have proved inadequate in understanding the physiological activities of proteins. One such enigmatic family of enzymes is the NUDIX ( cleoside phosphate linked to a moiety ) hydrolase family that has over 80000 members from all branches of the tree of life. Though MutT, the founding member of this family, was identified in 1954, we are only now beginning to understand the diversity of substrates and biological roles that these enzymes demonstrate. In a recent article by Cordeiro et al. in Bioscience Reports [Biosci. Rep. (2019)], two members of this protein family from the human pathogen were deorphanized as being polyphosphate hydrolases. The authors show that of the five NUDIX hydrolases coded by the genomes, TbNH2 and TbNH4, show hydrolytic activity against inorganic polyphosphate. Through classical biochemistry and immunostaining microscopy, differences in their substrate specificities and sub-cellular localization were revealed. These new data provide a compelling direction to the study of Trypanosome stress biology as well as our understanding of the NUDIX enzyme family.
在基因组学时代，序列信息呈爆炸式增长，出现了数千种没有功能注释的蛋白质序列。尽管我们仅根据序列预测功能的能力在稳步提高，但我们还有很长的路要走。具有共同进化起源的蛋白质具有明显的序列特征，这些特征应该能够揭示它们的生物学功能。这些序列特征使我们能够将蛋白质分类为具有相似结构且可能具有相似功能的家族。然而，进化是一个永恒的微调者，因此，仅序列特征不足以理解蛋白质的生理活动。NUDIX（核苷酸磷酸连接到某一部分）水解酶家族就是这样一个神秘的酶家族，它拥有来自生命之树各个分支的超过 80000 个成员。尽管这个家族的创始成员 MutT 于 1954 年被发现，但我们现在才开始了解这些酶表现出的多样性底物和生物学功能。在最近 Cordeiro 等人在《生物科学报告》（Biosci. Rep. (2019)）上的一篇文章中，人类病原体中的两个该蛋白家族成员被鉴定为多聚磷酸盐水解酶。作者表明，在 编码的 5 种 NUDIX 水解酶中，TbNH2 和 TbNH4 对无机多聚磷酸盐具有水解活性。通过经典的生物化学和免疫染色显微镜，揭示了它们在底物特异性和亚细胞定位上的差异。这些新数据为研究锥虫应激生物学以及我们对 NUDIX 酶家族的理解提供了一个引人注目的方向。
