Proteins are supposed to bind to their substrates/ligands in a specific manner via their pre-formed binding sites, according to classical biochemistry. In recent years, several types of deviations from this norm have been observed and called promiscuous behavior. Enzymatic promiscuities allow several biochemical functions to be carried out by the same enzyme. The promiscuous activity can also be the origin of “new proteins” via gene duplication. In more recent years, proteins from prokaryotes, eukaryotes and viruses have been found to have intrinsic disorder and lack a preformed binding site. Intrinsic disorder is exploited in regulatory proteins such as those that are involved in transcription and signal transduction. Such proteins function by folding locally while binding to their ligands or interacting with other proteins. These phenomena have also been classified as examples of protein promiscuity and encompass diverse kinds of ligands that can bind to a protein. Given the significant extent of structural homology in many protein families, it is not surprising that ligands also have been found to display promiscuity. Promiscuous behavior of proteins offers both challenges and opportunities to the drug discovery programs such as drug repurposing. Pathogens when exposed to antibiotics exploit protein promiscuity in several ways to develop resistance to the drug. There is increasing evidence now to support that the disorder in proteins is a major tool used by pathogens for virulence and evade drug action by exploiting protein promiscuity. This review provides a holistic view of this multi-faceted phenomenon called protein promiscuity.

根据经典的生物化学方法，蛋白质应通过其预先形成的结合位点以特定的方式与底物/配体结合。近年来，已观察到与该规范的几种类型的偏离，称为混杂行为。酶混用使得同一酶可以执行多种生化功能。混杂的活动也可以是“新的蛋白质”的由来通过基因重复。近年来，已经发现来自原核生物，真核生物和病毒的蛋白质具有内在的紊乱并且缺乏预先形成的结合位点。内在障碍被利用在调节蛋白中，例如那些参与转录和信号转导的蛋白。这样的蛋白质通过在与它们的配体结合或与其他蛋白质相互作用时局部折叠而起作用。这些现象也被归类为蛋白质混杂的例子，涵盖了可以与蛋白质结合的各种配体。考虑到许多蛋白质家族中结构同源性的程度很高，因此发现配体也显示混杂是不足为奇的。蛋白质的混杂行为给药物发现计划（例如重新利用药物）带来了挑战和机遇。当暴露于抗生素时，病原体会以多种方式利用蛋白质混杂，从而产生对药物的抗性。现在有越来越多的证据支持蛋白质失调是病原体利用毒力和滥用蛋白质来逃避药物作用的主要工具。这篇综述提供了对这种多方面现象的整体看法，这种现象被称为蛋白质滥交。