4fno | pdb_00004fno
Crystal structure of peptidyl t-RNA hydrolase from Pseudomonas aeruginosa at 2.2 Angstrom resolution
Structural highlights
Function[PTH_PSEAE] The natural substrate for this enzyme may be peptidyl-tRNAs which drop off the ribosome during protein synthesis (By similarity). Publication Abstract from PubMedDuring the course of protein synthesis in the cell, the translation process is often terminated due to various reasons. As a result, peptidyl-tRNA molecules are released which are toxic to the cell as well reducing the availability of free amino acid and tRNA molecules for the required protein synthesis in the cell. Such a situation is corrected by an enzyme, Pth (peptidyl-tRNA hydrolase), which catalyses the release of free tRNA and peptide moieties from peptidyl-tRNAs. This means that the active Pth is essential for the survival of bacteria. In order to design inhibitors of PaPth (Pth from Pseudomonas aeruginosa), we determined the structures of PaPth in its native and bound states with compounds amino acylate-tRNA analogue and 5-azacytidine. The structure determination of the native protein revealed that the substrate-binding site was partially occupied by Glu161 from the neigh-bouring molecule. The structure of PaPth indicated that the substrate-binding site can be broadly divided into three distinct subsites. The structures of the two complexes showed that the amino acylate-tRNA analogue filled three subsites, whereas 5-azacytidine filled two subsites. The common sugar and the base moieties of the two compounds occupied identical positions in the cleft. Using surface plasmon resonance, the dissociation constants for the amino acylate-tRNA analogue and 5-azacytidine were found to be 3.53x10-8 M and 5.82x10-8 M respectively. Structural and binding studies of peptidyl-tRNA hydrolase from Pseudomonas aeruginosa provide a platform for the structure-based inhibitor design against peptidyl-tRNA hydrolase.,Singh A, Kumar A, Gautam L, Sharma P, Sinha M, Bhushan A, Kaur P, Sharma S, Arora A, Singh TP Biochem J. 2014 Nov 1;463(3):329-37. doi: 10.1042/BJ20140631. PMID:25101795[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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