Mudryi Vitalii, Peske Frank, Rodnina Marina
Department of Physical Biochemistry, Max Planck Institute for Multidisciplinary Sciences, 37077 Goettingen, Germany.
BBA Adv. 2023 Jan 10;3:100074. doi: 10.1016/j.bbadva.2023.100074. eCollection 2023.
Elongation factor P (EF-P) and its eukaryotic homolog eIF5A are auxiliary translation factors that facilitate peptide bond formation when several sequential proline (Pro) residues are incorporated into the nascent chain. EF-P and eIF5A bind to the exit (E) site of the ribosome and contribute to favorable entropy of the reaction by stabilizing tRNA binding in the peptidyl transferase center of the ribosome. In most organisms, EF-P and eIF5A carry a posttranslational modification that is crucial for catalysis. The chemical nature of the modification varies between different groups of bacteria and between pro- and eukaryotes, making the EF-P-modification enzymes promising targets for antibiotic development. In this review, we summarize our knowledge of the structure and function of EF-P and eIF5A, describe their modification enzymes, and present an approach for potential drug screening aimed at EarP, an enzyme that is essential for EF-P modification in several pathogenic bacteria.
延伸因子P（EF-P）及其真核同源物eIF5A是辅助翻译因子，当几个连续的脯氨酸（Pro）残基掺入新生链时，它们促进肽键形成。EF-P和eIF5A与核糖体的出口（E）位点结合，并通过稳定核糖体肽基转移酶中心的tRNA结合来促进反应的有利熵变。在大多数生物体中，EF-P和eIF5A进行一种对催化至关重要的翻译后修饰。修饰的化学性质在不同细菌群体之间以及原核生物和真核生物之间有所不同，这使得EF-P修饰酶成为抗生素开发的有前景的靶点。在这篇综述中，我们总结了我们对EF-P和eIF5A的结构和功能的认识，描述了它们的修饰酶，并提出了一种针对EarP的潜在药物筛选方法，EarP是几种致病细菌中EF-P修饰所必需的一种酶。
