4ZER

Crystal structure of the Onc112 antimicrobial peptide bound to the Thermus thermophilus 70S ribosome

This is a non-PDB format compatible entry.

Summary for 4ZER

• Entry DOI: 10.2210/pdb4zer/pdb
• Descriptor: 23s ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (63 entities in total)
• Functional Keywords: bacterial ribosome, proline-rich antimicrobial peptide, antibiotics, protein biosynthesis, ribosome
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 110
• Total formula weight: 4412861.84

Authors

Seefeldt, A.C.,Nguyen, F.,Antunes, S.,Perebaskine, N.,Graf, M.,Arenz, S.,Inampudi, K.K.,Douat, C.,Guichard, G.,Wilson, D.N.,Innis, C.A. (deposition date: 2015-04-20, release date: 2015-05-20, Last modification date: 2024-04-24)

Primary citation

Seefeldt, A.C.,Nguyen, F.,Antunes, S.,Perebaskine, N.,Graf, M.,Arenz, S.,Inampudi, K.K.,Douat, C.,Guichard, G.,Wilson, D.N.,Innis, C.A.
The proline-rich antimicrobial peptide Onc112 inhibits translation by blocking and destabilizing the initiation complex.
Nat.Struct.Mol.Biol., 22:470-475, 2015

PubMed Abstract: The increasing prevalence of multidrug-resistant pathogenic bacteria is making current antibiotics obsolete. Proline-rich antimicrobial peptides (PrAMPs) display potent activity against Gram-negative bacteria and thus represent an avenue for antibiotic development. PrAMPs from the oncocin family interact with the ribosome to inhibit translation, but their mode of action has remained unclear. Here we have determined a structure of the Onc112 peptide in complex with the Thermus thermophilus 70S ribosome at a resolution of 3.1 Å by X-ray crystallography. The Onc112 peptide binds within the ribosomal exit tunnel and extends toward the peptidyl transferase center, where it overlaps with the binding site for an aminoacyl-tRNA. We show biochemically that the binding of Onc112 blocks and destabilizes the initiation complex, thus preventing entry into the elongation phase. Our findings provide a basis for the future development of this class of potent antimicrobial agents.

PubMed: 25984971
DOI: 10.1038/nsmb.3034

Experimental method

X-RAY DIFFRACTION (3.1 Å)