Protein-protein interactions often regulate the activity of protein kinases by allosterically modulating the conformation of the ATP-binding site. Bidirectional allostery implies that reverse modulation (i.e., from the ATP-binding site to the interaction and regulatory sites) must also be possible. Here, we review both the allosteric regulation of protein kinases and recent work describing how compounds binding at the ATP-binding site can promote or inhibit protein kinase interactions at regulatory sites via the reverse mechanism. Notably, the pharmaceutical industry has been developing compounds that bind to the ATP-binding site of protein kinases and potently disrupt protein-protein interactions between target protein kinases and their regulatory interacting partners. Learning to modulate allosteric processes will facilitate the development of protein-protein interaction modulators.

中文翻译：

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变构的复兴来破坏蛋白激酶的相互作用。

蛋白质间相互作用通常通过变构地调节ATP结合位点的构象来调节蛋白激酶的活性。双向变构意味着反向调制（即从ATP结合位点到相互作用和调控位点）也必须是可能的。在这里，我们回顾了蛋白激酶的变构调节和最近的工作，描述了化合物在ATP结合位点的结合如何通过反向机制促进或抑制蛋白激酶在调节位点的相互作用。值得注意的是，制药行业一直在开发与蛋白激酶的ATP结合位点结合并有效破坏目标蛋白激酶与其调节相互作用伙伴之间的蛋白相互作用的化合物。