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.

中文翻译：

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变构多能性：挑战与机遇

当变构受体对变构刺激的功能反应依赖于额外的变构调节剂时，变构多能性就会出现。在这里，我们讨论了在原型蛋白激酶 A (PKA) 以及其他信号系统中观察到的变构多能性，从典型的多域信号蛋白到细菌酶。我们确定了多能变构的关键驱动因素，并说明了假设变构多能性如何解决目前文献中存在的关于已知变构调节剂的双重性质的明显差异。我们还概述了变构多能性对细胞信号传导和变构药物设计的影响，并分析了变构多能性所带来的挑战和机遇。