4FNO

Crystal structure of peptidyl t-RNA hydrolase from Pseudomonas aeruginosa at 2.2 Angstrom resolution

Summary for 4FNO

• Entry DOI: 10.2210/pdb4fno/pdb
• Related: 4ERX
• Descriptor: Peptidyl-tRNA hydrolase, DI(HYDROXYETHYL)ETHER, GLYCEROL, ... (4 entities in total)
• Functional Keywords: hydrolase
• Biological source: Pseudomonas aeruginosa
• Cellular location: Cytoplasm : Q9HVC3
• Total number of polymer chains: 2
• Total formula weight: 42338.30

Authors

Singh, A.,Kumar, A.,Arora, A.,Singh, N.,Sinha, M.,Kaur, P.,Sharma, S.,Singh, T.P. (deposition date: 2012-06-20, release date: 2012-07-04, Last modification date: 2023-11-08)

Primary citation

Singh, A.,Kumar, A.,Gautam, L.,Sharma, P.,Sinha, M.,Bhushan, A.,Kaur, P.,Sharma, S.,Arora, A.,Singh, T.P.
Structural and binding studies of peptidyl-tRNA hydrolase from Pseudomonas aeruginosa provide a platform for the structure-based inhibitor design against peptidyl-tRNA hydrolase
Biochem.J., 463:329-337, 2014

PubMed Abstract: During 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 3.53×10-8 M and 5.82×10-8 M respectively.

PubMed: 25101795
DOI: 10.1042/BJ20140631

Experimental method

X-RAY DIFFRACTION (2.25 Å)