4QBK

Crystal structure of the complex of Peptidyl-tRNA hydrolase from Pseudomonas aeruginosa with amino acyl-tRNA analogue at 1.77 Angstrom resolution

4QBK の概要

• エントリーDOI: 10.2210/pdb4qbk/pdb
• 関連するPDBエントリー: 4JC4
• 分子名称: Peptidyl-tRNA hydrolase, GLYCEROL, 3'-deoxy-3'-[(O-methyl-L-tyrosyl)amino]adenosine, ... (4 entities in total)
• 機能のキーワード: pth, hydrolase
• 由来する生物種: Pseudomonas aeruginosa
• 細胞内の位置: Cytoplasm : Q9HVC3
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21368.34

構造登録者

Singh, A.,Sinha, M.,Bhushan, A.,Kaur, P.,Sharma, S.,Singh, T.P. (登録日: 2014-05-08, 公開日: 2014-05-28, 最終更新日: 2023-11-08)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.77 Å)