Laboratoire d'Ingénierie de Protéines et des Peptides, Louvain-la-Neuve, Belgium.
Chembiochem. 2009 Dec 14;10(18):2824-35. doi: 10.1002/cbic.200900590.
Enzymes and ribozymes constitute two classes of biological catalysts. The activity of many natural enzymes is regulated by the binding of ligands that have different structures than their substrates; these ligands are consequently called allosteric effectors. In most allosteric enzymes, the allosteric binding site lies far away from the active site. This implies that communication pathways must exist between these sites. While mechanisms of allosteric regulation were developed more than forty years ago, they continue to be revisited regularly. The improved understanding of these mechanisms has led in the past two decades to projects to transform several unregulated enzymes into allosterically regulated ones either by rational design or directed evolution techniques. More recently, ribozymes have also been the object of similar successful engineering efforts. In this review, after briefly summarising recent progress in the theories of allosteric regulation, several strategies to engineer allosteric regulations in enzymes and ribozymes are described and compared. These redesigned biological catalysts find applications in a variety of areas.
酶和核酶构成了两类生物催化剂。许多天然酶的活性受配体结合的调节，这些配体的结构与它们的底物不同；因此，这些配体被称为别构效应物。在大多数别构酶中，别构结合位点远离活性位点。这意味着这些位点之间必须存在通讯途径。虽然别构调节的机制早在四十多年前就已经发展起来，但它们仍在定期被重新研究。过去二十年中，对这些机制的理解的提高导致了通过合理设计或定向进化技术将几种未调节的酶转化为别构调节酶的项目。最近，核酶也成为了类似成功的工程设计的对象。在这篇综述中，在简要总结别构调节理论的最新进展之后，描述并比较了几种在酶和核酶中设计别构调节的策略。这些重新设计的生物催化剂在各种领域都有应用。
