5fdu

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

spinqualitylabelsall models 5fdu, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5fdu is a 20 chain structure with sequence from Thermus thermophilus HB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Ligands: 0TD, 2MA, 2MG, 4OC, 5MC, 5MU, 7MG, M2G, MA6, MG, OMG, OMU, PSU, SF4, UR3, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL2_THET8 One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial (By similarity). Makes several contacts with the 16S rRNA (forming bridge B7b) in the 70S ribosome.[HAMAP-Rule:MF_01320_B] Publication Abstract from PubMed Proline-rich antimicrobial peptides (PrAMPs) produced as part of the innate immune response of animals, insects and plants represent a vast, untapped resource for the treatment of multidrug-resistant bacterial infections. PrAMPs such as oncocin or bactenecin-7 (Bac7) interact with the bacterial ribosome to inhibit translation, but their supposed specificity as inhibitors of bacterial rather than mammalian protein synthesis remains unclear, despite being key to developing drugs with low toxicity. Here, we present crystal structures of the Thermus thermophilus 70S ribosome in complex with the first 16 residues of mammalian Bac7, as well as the insect-derived PrAMPs metalnikowin I and pyrrhocoricin. The structures reveal that the mammalian Bac7 interacts with a similar region of the ribosome as insect-derived PrAMPs. Consistently, Bac7 and the oncocin derivative Onc112 compete effectively with antibiotics, such as erythromycin, which target the ribosomal exit tunnel. Moreover, we demonstrate that Bac7 allows initiation complex formation but prevents entry into the elongation phase of translation, and show that it inhibits translation on both mammalian and bacterial ribosomes, explaining why this peptide needs to be stored as an inactive pro-peptide. These findings highlight the need to consider the specificity of PrAMP derivatives for the bacterial ribosome in future drug development efforts. Structure of the mammalian antimicrobial peptide Bac7(1-16) bound within the exit tunnel of a bacterial ribosome.,Seefeldt AC, Graf M, Perebaskine N, Nguyen F, Arenz S, Mardirossian M, Scocchi M, Wilson DN, Innis CA Nucleic Acids Res. 2016 Jan 20. pii: gkv1545. PMID:26792896 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA