5T7V

Methicillin Resistant, Linezolid resistant Staphylococcus aureus 70S ribosome (delta S145 uL3)

This is a non-PDB format compatible entry.

Summary for 5T7V

• Entry DOI: 10.2210/pdb5t7v/pdb
• EMDB information: 8369
• Descriptor: 16S ribosomal RNA, 30S ribosomal protein S4, 30S ribosomal protein S5, ... (43 entities in total)
• Functional Keywords: 70s ribosome, methicillin resistant, linezolid resistant, cryoem, ribosome
• Biological source: Staphylococcus aureus; More
• Total number of polymer chains: 42
• Total formula weight: 1971153.05

Authors

Belousoff, M.J.,Lithgow, T.,Eyal, Z.,Yonath, A.,Radjainia, M. (deposition date: 2016-09-06, release date: 2017-05-31, Last modification date: 2024-10-09)

Primary citation

Belousoff, M.J.,Eyal, Z.,Radjainia, M.,Ahmed, T.,Bamert, R.S.,Matzov, D.,Bashan, A.,Zimmerman, E.,Mishra, S.,Cameron, D.,Elmlund, H.,Peleg, A.Y.,Bhushan, S.,Lithgow, T.,Yonath, A.
Structural Basis for Linezolid Binding Site Rearrangement in theStaphylococcus aureusRibosome.
MBio, 8:-, 2017

PubMed Abstract: 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 This high-resolution structural information demonstrated that a single amino acid deletion in ribosomal protein uL3 confers linezolid resistance despite being located 24 Å 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. The growing burden on human health caused by various antibiotic resistance mutations now includes prevalent 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.

PubMed: 28487427
DOI: 10.1128/mBio.00395-17

Experimental method

ELECTRON MICROSCOPY (3.6 Å)