5W4K

Crystal structure of the Thermus thermophilus 70S ribosome in complex with Klebsazolicin and bound to mRNA and A-, P- and E-site tRNAs at 2.7A resolution

This is a non-PDB format compatible entry.

Summary for 5W4K

• Entry DOI: 10.2210/pdb5w4k/pdb
• Related PRD ID: PRD_002277
• Descriptor: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (63 entities in total)
• Functional Keywords: klebsazolicin, antibiotic, ripps, ribosome inhibitor, 70s ribosome, inhibition of translation, peptidyl transferase center, nascent peptide exit tunnel, ribosome-antibiotic complex, ribosome/antibiotic
• Biological source: Escherichia coli; More
• Total number of polymer chains: 114
• Total formula weight: 4576710.22

Authors

Metelev, M.,Osterman, I.A.,Ghilarov, D.,Khabibullina, N.F.,Yakimov, A.,Shabalin, K.,Utkina, I.,Travin, D.Y.,Komarova, E.S.,Serebryakova, M.,Artamonova, T.,Khodorkovskii, M.,Konevega, A.L.,Sergiev, P.V.,Severinov, K.,Polikanov, Y.S. (deposition date: 2017-06-12, release date: 2017-08-30, Last modification date: 2025-04-02)

Primary citation

Metelev, M.,Osterman, I.A.,Ghilarov, D.,Khabibullina, N.F.,Yakimov, A.,Shabalin, K.,Utkina, I.,Travin, D.Y.,Komarova, E.S.,Serebryakova, M.,Artamonova, T.,Khodorkovskii, M.,Konevega, A.L.,Sergiev, P.V.,Severinov, K.,Polikanov, Y.S.
Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel.
Nat. Chem. Biol., 13:1129-1136, 2017

PubMed Abstract: Whereas screening of the small-molecule metabolites produced by most cultivatable microorganisms often results in the rediscovery of known compounds, genome-mining programs allow researchers to harness much greater chemical diversity, and result in the discovery of new molecular scaffolds. Here we report the genome-guided identification of a new antibiotic, klebsazolicin (KLB), from Klebsiella pneumoniae that inhibits the growth of sensitive cells by targeting ribosomes. A ribosomally synthesized post-translationally modified peptide (RiPP), KLB is characterized by the presence of a unique N-terminal amidine ring that is essential for its activity. Biochemical in vitro studies indicate that KLB inhibits ribosomes by interfering with translation elongation. Structural analysis of the ribosome-KLB complex showed that the compound binds in the peptide exit tunnel overlapping with the binding sites of macrolides or streptogramin-B. KLB adopts a compact conformation and largely obstructs the tunnel. Engineered KLB fragments were observed to retain in vitro activity, and thus have the potential to serve as a starting point for the development of new bioactive compounds.

PubMed: 28846667
DOI: 10.1038/nchembio.2462

Experimental method

X-RAY DIFFRACTION (2.7 Å)