Structural and functional insights into peptidyl-tRNA hydrolase.
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.
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Sujata
S
Sharma
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Sanket
S
Kaushik
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Mau
M
Sinha
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Gajraj Singh
GS
Kushwaha
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Avinash
A
Singh
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Juhi
J
Sikarwar
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Anshul
A
Chaudhary
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Akshita
A
Gupta
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India.
Punit
P
Kaur
Department of Biophysics, All India Institute of Medical Sciences, New Delhi 110029, India. Electronic address: tpsingh.aiims@gmail.com.
Tej P
TP
Singh
D001419:Bacteria / Q000201:enzymology*; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D006868:Hydrolysis; D013379:Substrate Specificity
D002265:Carboxylic Ester Hydrolases; C019674:aminoacyl-tRNA hydrolase
Peptidyl-tRNA hydrolase; Pth; Pth2; Stalled ribosome; Structure