细菌肽基tRNA水解酶(Pth)或Pth1作为关键酶出现,通过催化肽基-tRNA分子释放肽基部分和维持特定tRNA的游离库,参与维持细胞稳态。这种酶对细菌细胞和各种细菌感染的新兴药物靶标至关重要。了解细菌Pth的酶促机制和结构复杂性对于设计新疗法以对抗抗生素耐药性至关重要。这篇综述全面分析了Pth在细菌生理学中的多方面作用,阐明其作为潜在药物靶标的重要性。本文深入研究了Pth的各种功能,包括参与核糖体拯救,在细菌系统中维持一个自由的tRNA池,翻译保真度的规定,和细菌系统内的应激反应途径。此外,它还探索了细菌Pth的可药用性,强调其作为抗菌剂靶标的前景,并强调与开发针对该酶的特异性抑制剂相关的挑战。结构阐明是揭示Pth的催化机理和底物识别的基石。这篇综述概括了通过各种生物物理技术获得的Pth的当前结构见解,如X射线晶体学和核磁共振光谱,提供对酶的结构和构象动力学的详细了解。此外,生物物理方面,包括它与配体的相互作用,抑制剂,和基底,讨论,阐明细菌Pth功能的分子基础及其在药物设计策略中的潜在用途。通过这篇评论文章,我们的目标是汇集所有有关细菌Pth的现有信息,并强调其在推进创新治疗干预措施和对抗细菌感染方面的潜力。
Bacterial peptidyl tRNA hydrolase (Pth) or Pth1 emerges as a pivotal enzyme involved in the maintenance of cellular homeostasis by catalyzing the release of peptidyl moieties from peptidyl-tRNA molecules and the maintenance of a free pool of specific tRNAs. This enzyme is vital for bacterial cells and an emerging drug target for various bacterial infections. Understanding the enzymatic mechanisms and structural intricacies of bacterial Pth is pivotal in designing novel therapeutics to combat antibiotic resistance. This review provides a comprehensive analysis of the multifaceted roles of Pth in bacterial physiology, shedding light on its significance as a potential drug target. This article delves into the diverse functions of Pth, encompassing its involvement in ribosome rescue, the maintenance of a free tRNA pool in bacterial systems, the regulation of translation fidelity, and stress response pathways within bacterial systems. Moreover, it also explores the druggability of bacterial Pth, emphasizing its promise as a target for antibacterial agents and highlighting the challenges associated with developing specific inhibitors against this enzyme. Structural elucidation represents a cornerstone in unraveling the catalytic mechanisms and substrate recognition of Pth. This review encapsulates the current structural insights of Pth garnered through various biophysical techniques, such as X-ray crystallography and NMR spectroscopy, providing a detailed understanding of the enzyme\'s architecture and conformational dynamics. Additionally, biophysical aspects, including its interaction with ligands, inhibitors, and substrates, are discussed, elucidating the molecular basis of bacterial Pth\'s function and its potential use in drug design strategies. Through this review article, we aim to put together all the available information on bacterial Pth and emphasize its potential in advancing innovative therapeutic interventions and combating bacterial infections.