Biotechnology and Biosciences Research Group, School of Chemical Sciences and Engineering, Autonomous University of Baja California, Tijuana 22390, Mexico.
Int J Mol Sci. 2023 Jul 26;24(15):11992. doi: 10.3390/ijms241511992.
TOR proteins, also known as targets of rapamycin, are serine/threonine kinases involved in various signaling pathways that regulate cell growth. The protozoan parasite is the causative agent of giardiasis, a neglected infectious disease in humans. In this study, we used a bioinformatics approach to examine the structural features of GTOR, a TOR-like protein, and predict functional associations. Our findings confirmed that it shares significant similarities with functional TOR kinases, including a binding domain for the FKBP-rapamycin complex and a kinase domain resembling that of phosphatidylinositol 3-kinase-related kinases. In addition, it can form multiprotein complexes such as TORC1 and TORC2. These results provide valuable insights into the structure-function relationship of GTOR, highlighting its potential as a molecular target for controlling cell proliferation. Furthermore, our study represents a step toward rational drug design for specific anti-giardiasis therapeutic agents.
TOR 蛋白,也称为雷帕霉素的靶点,是丝氨酸/苏氨酸激酶,参与调节细胞生长的各种信号通路。原生动物寄生虫是贾第虫病的病原体,这是一种在人类中被忽视的传染病。在这项研究中,我们使用生物信息学方法研究了 GTOR,一种 TOR 样蛋白的结构特征,并预测了其功能关联。我们的研究结果证实,它与功能性 TOR 激酶具有显著的相似性,包括与 FKBP-雷帕霉素复合物结合的结构域和与磷酸肌醇 3-激酶相关激酶相似的激酶结构域。此外,它可以形成 TORC1 和 TORC2 等多蛋白复合物。这些结果为 GTOR 的结构-功能关系提供了有价值的见解,突出了其作为控制细胞增殖的分子靶标的潜力。此外,我们的研究代表了朝着针对特定抗贾第虫病治疗药物的合理药物设计迈出的一步。