Byrne Dominic P, Foulkes Daniel M, Eyers Patrick A
Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
Future Med Chem. 2017 Jan;9(2):245-265. doi: 10.4155/fmc-2016-0207. Epub 2017 Jan 18.
The pseudokinase complement of the human kinase superfamily consists of approximately 60 signaling proteins, which lacks one or more of the amino acids typically required to correctly align ATP and metal ions, and phosphorylate protein substrates. Recent studies in the pseudokinase field have begun to expose the biological relevance of pseudokinases, which are now thought to perform a diverse range of physiological roles and are connected to a multitude of human diseases, including cancer. In this review, we discuss how and why members of the 'pseudokinome' represent important new targets for drug discovery, and describe how knowledge of protein structure and function provides informative clues to help guide the rational chemical design or repurposing of inhibitors to target pseudokinases.
人类激酶超家族的伪激酶成员约由60种信号蛋白组成,这些蛋白缺少正确排列ATP和金属离子以及磷酸化蛋白质底物通常所需的一种或多种氨基酸。最近在伪激酶领域的研究已开始揭示伪激酶的生物学相关性,现在认为它们发挥着多种生理作用,并与包括癌症在内的多种人类疾病相关。在本综述中,我们讨论了“伪激酶组”成员如何以及为何成为药物发现的重要新靶点,并描述了蛋白质结构和功能的知识如何提供有用线索,以帮助指导针对伪激酶的抑制剂的合理化学设计或重新利用。