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Crystal structure of the Onc112 antimicrobial peptide bound to the Thermus thermophilus 70S ribosomeCrystal structure of the Onc112 antimicrobial peptide bound to the Thermus thermophilus 70S ribosome
Structural highlights
FunctionRL24_THET8 One of two assembly initiator proteins, it binds directly to the 5'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit (By similarity).[HAMAP-Rule:MF_01326_B] One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit.[HAMAP-Rule:MF_01326_B] Publication Abstract from PubMedThe 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 A 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. The proline-rich antimicrobial peptide Onc112 inhibits translation by blocking and destabilizing the initiation complex.,Seefeldt AC, Nguyen F, Antunes S, Perebaskine N, Graf M, Arenz S, Inampudi KK, Douat C, Guichard G, Wilson DN, Innis CA Nat Struct Mol Biol. 2015 May 18. doi: 10.1038/nsmb.3034. PMID:25984971[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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