Allosteric regulation of protein functions is ubiquitous in organismal biology, but the principles governing its evolution are not well understood. Here we discuss recent studies supporting the large-scale existence of latent allostery in ancestor proteins of superfamilies. As suggested, the evolution of allostery could be driven by the need for specificity in paralogs of slow evolving protein complexes with conserved active sites. The same slow evolution is displayed by purifying selection exhibited in allosteric proteins with somatic mutations involved in cancer, where disease-associated mutations are enriched in both orthosteric and allosteric sites. Consequently, disease-associated variants can be used to identify druggable allosteric sites that are specific for paralogs in protein superfamilies with otherwise similar functions.

中文翻译：

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最近的进展表明选择压力在变构中的影响增加。

蛋白质功能的变构调节在生物体生物学中无处不在，但控制其进化的原理尚不清楚。在这里，我们讨论了支持超家族祖先蛋白质中潜在变构的大规模存在的最新研究。正如所建议的，变构的进化可能是由于对具有保守活性位点的缓慢进化的蛋白质复合物的旁系同源物的特异性的需要。通过纯化变构蛋白中表现出的与癌症相关的体细胞突变的选择，显示了相同的缓慢进化，其中疾病相关的突变在正构位点和变构位点中都富集。因此，疾病相关变体可用于鉴定具有其他相似功能的蛋白质超家族中旁系同源物的特异性药物变构位点。