4Z8C

Crystal structure of the Thermus thermophilus 70S ribosome bound to translation inhibitor oncocin

This is a non-PDB format compatible entry.

Summary for 4Z8C

• Entry DOI: 10.2210/pdb4z8c/pdb
• Descriptor: 23S ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (59 entities in total)
• Functional Keywords: oncocin, antimicrobial peptide, antibiotic, 70s ribosome, inhibition of translation, peptidyl transferase inhibitors, 50s ribosomal subunit, peptide exit tunnel, ribosome-inhibitor complex, onc112, ribosome-antibiotic complex, ribosome/antibiotic
• Biological source: Escherichia coli; More
• Total number of polymer chains: 110
• Total formula weight: 4464601.48

Authors

Roy, R.N.,Lomakin, I.B.,Gagnon, M.G.,Steitz, T.A. (deposition date: 2015-04-08, release date: 2015-05-20, Last modification date: 2024-03-06)

Primary citation

Roy, R.N.,Lomakin, I.B.,Gagnon, M.G.,Steitz, T.A.
The mechanism of inhibition of protein synthesis by the proline-rich peptide oncocin.
Nat.Struct.Mol.Biol., 22:466-469, 2015

PubMed Abstract: Antibiotic-resistant bacteria are a global health issue necessitating the development of new effective therapeutics. Proline-rich antimicrobial peptides (PrAMPs), which include oncocins, are an extensively studied class of AMPs that counteract bacterial infection at submicromolar concentrations. Oncocins enter and kill bacteria by inhibiting certain targets rather than by acting through membrane lysis. Although they have recently been reported to bind DnaK and the bacterial ribosome, their mode of inhibition has remained elusive. Here we report the crystal structure of the oncocin derivative Onc112 bound to the Thermus thermophilus 70S ribosome. Strikingly, this 19-residue proline-rich peptide manifests the features of several known classes of ribosome inhibitors by simultaneously blocking the peptidyl transferase center and the peptide-exit tunnel of the ribosome. This high-resolution structure thus reveals the mechanism by which oncocins inhibit protein synthesis, providing an opportunity for structure-based design of new-generation therapeutics.

PubMed: 25984972
DOI: 10.1038/nsmb.3031

Experimental method

X-RAY DIFFRACTION (2.9 Å)