5t7v
Methicillin Resistant, Linezolid resistant Staphylococcus aureus 70S ribosome (delta S145 uL3)
Structural highlights
FunctionA0A077UKD6_9STAP Located on the platform of the 30S subunit, it bridges several disparate RNA helices of the 16S rRNA. Forms part of the Shine-Dalgarno cleft in the 70S ribosome.[HAMAP-Rule:MF_01310] Publication Abstract from PubMedAn 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||
