Sharma Sujata, Kaushik Sanket, Sinha Mau, Kushwaha Gajraj Singh, Singh Avinash, Sikarwar Juhi, Chaudhary Anshul, Gupta Akshita, Kaur Punit, Singh Tej P
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Biochim Biophys Acta. 2014 Jul;1844(7):1279-88. doi: 10.1016/j.bbapap.2014.04.012. Epub 2014 Apr 21.
Peptidyl-tRNA hydrolase is an essential enzyme which acts as one of the rescue factors of the stalled ribosomes. It is an esterase that hydrolyzes the ester bond in the peptidyl-tRNA molecules, which are products of ribosome stalling. This enzyme is required for rapid clearing of the peptidyl-tRNAs, the accumulation of which in the cell leads to cell death. Over the recent years, it has been heralded as an attractive drug target for antimicrobial therapeutics. Two distinct classes of peptidyl-tRNA hydrolase, Pth and Pth2, have been identified in nature. This review gives an overview of the structural and functional aspects of Pth, along with its sequence and structural comparison among various species of bacteria. While the mode of binding of the substrate to Pth and the mechanism of hydrolysis are still speculated upon, the structure-based drug design using this protein as the target is still largely unexplored. This review focuses on the structural features of Pth, giving a direction to structure-based drug design on this protein.
肽基 - tRNA水解酶是一种必需酶，作为停滞核糖体的拯救因子之一发挥作用。它是一种酯酶，可水解肽基 - tRNA分子中的酯键，这些分子是核糖体停滞的产物。快速清除肽基 - tRNA需要这种酶，其在细胞中的积累会导致细胞死亡。近年来，它被誉为抗菌治疗中有吸引力的药物靶点。自然界中已鉴定出两类不同的肽基 - tRNA水解酶，即Pth和Pth2。本综述概述了Pth的结构和功能方面，以及不同细菌物种之间的序列和结构比较。虽然底物与Pth的结合模式和水解机制仍在推测中，但以该蛋白为靶点的基于结构的药物设计仍在很大程度上未被探索。本综述重点关注Pth的结构特征，为基于该蛋白的结构药物设计指明方向。
