Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Ontario, Canada.
Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Biochem J. 2022 Apr 14;479(7):825-838. doi: 10.1042/BCJ20210528.
Allosteric pluripotency arises when the functional response of an allosteric receptor to an allosteric stimulus depends on additional allosteric modulators. Here, we discuss allosteric pluripotency as observed in the prototypical Protein Kinase A (PKA) as well as in other signaling systems, from typical multidomain signaling proteins to bacterial enzymes. We identify key drivers of pluripotent allostery and illustrate how hypothesizing allosteric pluripotency may solve apparent discrepancies currently present in the literature regarding the dual nature of known allosteric modulators. We also outline the implications of allosteric pluripotency for cellular signaling and allosteric drug design, and analyze the challenges and opportunities opened by the pluripotent nature of allostery.
变构多效性是指变构受体对变构刺激的功能反应取决于其他变构调节剂时出现的情况。在这里，我们讨论了在典型的蛋白激酶 A（PKA）以及其他信号转导系统中观察到的变构多效性，这些系统包括典型的多结构域信号蛋白和细菌酶。我们确定了变构多效性的关键驱动因素，并说明了假设变构多效性如何解决当前文献中关于已知变构调节剂双重性质的明显差异。我们还概述了变构多效性对细胞信号转导和变构药物设计的影响，并分析了变构多效性的多效性带来的挑战和机遇。
