7p7s

PoxtA-EQ2 antibiotic resistance ABCF bound to E. faecalis 70S ribosome, state II

spinqualitylabelsall models 7p7s, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7p7s is a 10 chain structure with sequence from Enterococcus faecalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3Å Ligands: ATP, K, MG, PUT, SCM, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A1B4XKV0_ENTFL Publication Abstract from PubMed PoxtA and OptrA are ATP binding cassette (ABC) proteins of the F subtype (ABCF). They confer resistance to oxazolidinone and phenicol antibiotics, such as linezolid and chloramphenicol, which stall translating ribosomes when certain amino acids are present at a defined position in the nascent polypeptide chain. These proteins are often encoded on mobile genetic elements, facilitating their rapid spread amongst Gram-positive bacteria, and are thought to confer resistance by binding to the ribosome and dislodging the bound antibiotic. However, the mechanistic basis of this resistance remains unclear. Here we refine the PoxtA spectrum of action, demonstrate alleviation of linezolid-induced context-dependent translational stalling, and present cryo-electron microscopy structures of PoxtA in complex with the Enterococcus faecalis 70S ribosome. PoxtA perturbs the CCA-end of the P-site tRNA, causing it to shift by approximately 4 A out of the ribosome, corresponding to a register shift of approximately one amino acid for an attached nascent polypeptide chain. We postulate that the perturbation of the P-site tRNA by PoxtA thereby alters the conformation of the attached nascent chain to disrupt the drug binding site. Structural basis for PoxtA-mediated resistance to phenicol and oxazolidinone antibiotics.,Crowe-McAuliffe C, Murina V, Turnbull KJ, Huch S, Kasari M, Takada H, Nersisyan L, Sundsfjord A, Hegstad K, Atkinson GC, Pelechano V, Wilson DN, Hauryliuk V Nat Commun. 2022 Apr 6;13(1):1860. doi: 10.1038/s41467-022-29274-9. PMID:35387982 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures

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