7JQL

Crystal structure of the Thermus thermophilus 70S ribosome in complex with Bac7-001, mRNA, and deacylated P-site tRNA at 3.00A resolution

これはPDB形式変換不可エントリーです。

7JQL の概要

• エントリーDOI: 10.2210/pdb7jql/pdb
• 分子名称: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (60 entities in total)
• 機能のキーワード: bactenecin 7; antibiotic; 70s ribosome; x-ray structure; inhibition of translation; peptidyl transferase center; nascent peptide exit tunnel, ribosome
• 由来する生物種: Thermus thermophilus HB8; 詳細
• タンパク質・核酸の鎖数: 110
• 化学式量合計: 4469975.75

構造登録者

Mardirossian, M.,Sola, R.,Beckert, B.,Valencic, E.,Collis, D.W.P.,Borisek, J.,Armas, F.,Di Stasi, A.,Buchmann, J.,Syroegin, E.A.,Polikanov, Y.S.,Magistrato, A.,Hilpert, K.,Wilson, D.N.,Scocchi, M. (登録日: 2020-08-11, 公開日: 2020-08-26, 最終更新日: 2023-11-15)

主引用文献

Mardirossian, M.,Sola, R.,Beckert, B.,Valencic, E.,Collis, D.W.P.,Borisek, J.,Armas, F.,Di Stasi, A.,Buchmann, J.,Syroegin, E.A.,Polikanov, Y.S.,Magistrato, A.,Hilpert, K.,Wilson, D.N.,Scocchi, M.
Peptide Inhibitors of Bacterial Protein Synthesis with Broad Spectrum and SbmA-Independent Bactericidal Activity against Clinical Pathogens.
J.Med.Chem., 63:9590-9602, 2020

PubMed Abstract: Proline-rich antimicrobial peptides (PrAMPs) are promising lead compounds for developing new antimicrobials; however, their narrow spectrum of action is limiting. PrAMPs kill bacteria binding to their ribosomes and inhibiting protein synthesis. In this study, 133 derivatives of the PrAMP Bac7(1-16) were synthesized to identify the crucial residues for ribosome inactivation and antimicrobial activity. Then, five new Bac7(1-16) derivatives were conceived and characterized by antibacterial and membrane permeabilization assays, X-ray crystallography, and molecular dynamics simulations. Some derivatives displayed broad spectrum activity, encompassing , , , , and . Two peptides out of five acquired a weak membrane-perturbing activity while maintaining the ability to inhibit protein synthesis. These derivatives became independent of the SbmA transporter, commonly used by native PrAMPs, suggesting that they obtained a novel route to enter bacterial cells. PrAMP-derived compounds could become new-generation antimicrobials to combat antibiotic-resistant pathogens.

PubMed: 32787108
DOI: 10.1021/acs.jmedchem.0c00665

実験手法

X-RAY DIFFRACTION (3 Å)