7JQM

Crystal structure of the Thermus thermophilus 70S ribosome in complex with Bac7-002, mRNA, and deacylated P-site tRNA at 3.05A resolution

This is a non-PDB format compatible entry.

Summary for 7JQM

• Entry DOI: 10.2210/pdb7jqm/pdb
• Descriptor: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (60 entities in total)
• Functional Keywords: bactenecin 7; antibiotic; 70s ribosome; x-ray structure; inhibition of translation; peptidyl transferase center; nascent peptide exit tunnel, ribosome
• Biological source: Thermus thermophilus HB8; More
• Total number of polymer chains: 110
• Total formula weight: 4456995.52

Authors

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. (deposition date: 2020-08-11, release date: 2020-08-26, Last modification date: 2025-03-19)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.05 Å)