Table1_Structural Basis for Allostery in PLP-dependent Enzymes.docx

Pyridoxal 5′-phosphate (PLP)-dependent enzymes are found ubiquitously in nature and are involved in a variety of biological pathways, from natural product synthesis to amino acid and glucose metabolism. The first structure of a PLP-dependent enzyme was reported over 40 years ago, and since that time, there is a steady wealth of structural and functional information revealed for a wide array of these enzymes. A functional mechanism that is gaining more appreciation due to its relevance in drug design is that of protein allostery, where binding of a protein or ligand at a distal site influences the structure, organization, and function at the active site. Here, we present a review of current structure-based mechanisms of allostery for select members of each PLP-dependent enzyme family. Knowledge of these mechanisms may have a larger potential for identifying key similarities and differences among enzyme families that can eventually be exploited for therapeutic development.

吡哆醛-5′-磷酸（PLP）依赖性酶在自然界中普遍存在，并参与多种生物途径，从天然产物合成至氨基酸和葡萄糖代谢。PLP依赖性酶的第一种结构在40多年前首次被报道，自那时起，关于这些酶的广泛族系，在结构及功能信息方面逐渐积累。由于其在药物设计中的相关性，蛋白质变构机制正日益受到重视，其中蛋白质或配体在远端位点的结合会影响活性位点的结构、组织和功能。在此，我们综述了针对每个PLP依赖性酶家族选定成员的基于结构的变构机制。对这些机制的了解可能具有更大的潜力，有助于识别酶家族之间的关键相似性和差异性，最终可被用于药物开发。