8R6C

70S Escherichia coli ribosome with Paenilamicin B2 bound with A- and P-site tRNA.

This is a non-PDB format compatible entry.

Summary for 8R6C

• Entry DOI: 10.2210/pdb8r6c/pdb
• Related: 8R8M 9FBV
• EMDB information: 18950
• Related PRD ID: PRD_002555
• Descriptor: Large ribosomal subunit protein bL33, Small ribosomal subunit protein uS4, Small ribosomal subunit protein uS5, ... (61 entities in total)
• Functional Keywords: ribosome, 70s, paenilamicin, antibiotic
• Biological source: Escherichia coli BW25113; More
• Total number of polymer chains: 57
• Total formula weight: 2226522.93

Authors

Koller, T.O.,Wilson, D.N. (deposition date: 2023-11-22, release date: 2024-07-24, Last modification date: 2025-03-12)

Primary citation

Koller, T.O.,Berger, M.J.,Morici, M.,Paternoga, H.,Bulatov, T.,Di Stasi, A.,Dang, T.,Mainz, A.,Raulf, K.,Crowe-McAuliffe, C.,Scocchi, M.,Mardirossian, M.,Beckert, B.,Vazquez-Laslop, N.,Mankin, A.,Sussmuth, R.D.,Wilson, D.N.
Paenilamicins from the honey bee pathogen Paenibacillus larvae are context-specific translocation inhibitors of protein synthesis.
Biorxiv, 2024

PubMed Abstract: The paenilamicins are a group of hybrid non-ribosomal peptide-polyketide compounds produced by the honey bee pathogen that display activity against Gram-positive pathogens, such as . While paenilamicins have been shown to inhibit protein synthesis, their mechanism of action has remained unclear. Here, we have determined structures of the paenilamicin PamB2 stalled ribosomes, revealing a unique binding site on the small 30S subunit located between the A- and P-site tRNAs. In addition to providing a precise description of interactions of PamB2 with the ribosome, the structures also rationalize the resistance mechanisms utilized by . We could further demonstrate that PamB2 interferes with the translocation of mRNA and tRNAs through the ribosome during translation elongation, and that this inhibitory activity is influenced by the presence of modifications at position 37 of the A-site tRNA. Collectively, our study defines the paenilamicins as a new class of context-specific translocation inhibitors.

PubMed: 38826346
DOI: 10.1101/2024.05.21.595107

Experimental method

ELECTRON MICROSCOPY (2.2 Å)