5tcu

Methicillin sensitive Staphylococcus aureus 70S ribosomeMethicillin sensitive Staphylococcus aureus 70S ribosome

5tcu, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Structural highlights 5tcu is a 10 chain structure with sequence from Staphylococcus aureus subsp. aureus NCTC 8325. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.9Å Ligands: Experimental data: Check Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RS3_STAA8 Binds the lower part of the 30S subunit head. Binds mRNA in the 70S ribosome, positioning it for translation. Publication Abstract from PubMed An unorthodox, surprising mechanism of resistance to the antibiotic linezolid was revealed by cryo-electron microscopy (cryo-EM) in the 70S ribosomes from a clinical isolate of Staphylococcus aureus This high-resolution structural information demonstrated that a single amino acid deletion in ribosomal protein uL3 confers linezolid resistance despite being located 24 A away from the linezolid binding pocket in the peptidyl-transferase center. The mutation induces a cascade of allosteric structural rearrangements of the rRNA that ultimately results in the alteration of the antibiotic binding site.IMPORTANCE The growing burden on human health caused by various antibiotic resistance mutations now includes prevalent Staphylococcus aureus resistance to last-line antimicrobial drugs such as linezolid and daptomycin. Structure-informed drug modification represents a frontier with respect to designing advanced clinical therapies, but success in this strategy requires rapid, facile means to shed light on the structural basis for drug resistance (D. Brown, Nat Rev Drug Discov 14:821-832, 2015, https://doi.org/10.1038/nrd4675). Here, detailed structural information demonstrates that a common mechanism is at play in linezolid resistance and provides a step toward the redesign of oxazolidinone antibiotics, a strategy that could thwart known mechanisms of linezolid resistance. Structural Basis for Linezolid Binding Site Rearrangement in the Staphylococcus aureus Ribosome.,Belousoff MJ, Eyal Z, Radjainia M, Ahmed T, Bamert RS, Matzov D, Bashan A, Zimmerman E, Mishra S, Cameron D, Elmlund H, Peleg AY, Bhushan S, Lithgow T, Yonath A MBio. 2017 May 9;8(3). pii: e00395-17. doi: 10.1128/mBio.00395-17. PMID:28487427 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures