PDF(Pubmed)
Abstract：
Targeting translation factor proteins holds promise for developing innovative anti-tuberculosis drugs. During protein translation, many factors cause ribosomes to stall at messenger RNA (mRNA). To maintain protein homeostasis, bacteria have evolved various ribosome rescue mechanisms, including the predominant trans-translation process, to release stalled ribosomes and remove aberrant mRNAs. The rescue systems require the participation of translation elongation factor proteins (EFs) and are essential for bacterial physiology and reproduction. However, they disappear during eukaryotic evolution, which makes the essential proteins and translation elongation factors promising antimicrobial drug targets. Here, we review the structural and molecular mechanisms of the translation elongation factors EF-Tu, EF-Ts, and EF-G, which play essential roles in the normal translation and ribosome rescue mechanisms of Mycobacterium tuberculosis (Mtb). We also briefly describe the structure-based, computer-assisted study of anti-tuberculosis drugs.
摘要：
靶向翻译因子蛋白有望开发创新的抗结核药物。在蛋白质翻译过程中,许多因素导致核糖体在信使RNA（mRNA）处停滞。为了维持蛋白质的稳态,细菌已经进化出各种核糖体拯救机制，包括主要的翻译过程，释放停滞的核糖体并去除异常的mRNA。拯救系统需要翻译延伸因子蛋白（EF）的参与，并且对于细菌生理和繁殖至关重要。然而,它们在真核进化过程中消失，这使得必需蛋白和翻译延伸因子有望成为抗菌药物的靶点。这里,我们综述了翻译延伸因子EF-Tu的结构和分子机制，EF-Ts,和EF-G,在结核分枝杆菌（Mtb）的正常翻译和核糖体拯救机制中起着至关重要的作用。我们还简要描述了基于结构的，计算机辅助抗结核药物研究。
