5TCU の概要
| エントリーDOI | 10.2210/pdb5tcu/pdb |
| EMDBエントリー | 8369 8402 |
| 分子名称 | 16S RRNA, 30S ribosomal protein S11, 30S ribosomal protein S12, ... (54 entities in total) |
| 機能のキーワード | 70s ribosome, cryoem, ribosome, staphylococcus aureus, ribosome-antibiotic complex, ribosome/antibiotic |
| 由来する生物種 | Staphylococcus aureus (strain NCTC 8325) 詳細 |
| タンパク質・核酸の鎖数 | 52 |
| 化学式量合計 | 2119582.33 |
| 構造登録者 | Eyal, Z.,Ahmed, T.,Belousoff, N.,Mishra, S.,Matzov, D.,Bashan, A.,Zimmerman, E.,Lithgow, T.,Bhushan, S.,Yonath, A. (登録日: 2016-09-15, 公開日: 2017-05-24, 最終更新日: 2025-05-21) |
| 主引用文献 | 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 the Staphylococcus aureus Ribosome. MBio, 8:-, 2017 Cited by 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: 28487427DOI: 10.1128/mBio.00395-17 主引用文献が同じPDBエントリー |
| 実験手法 | ELECTRON MICROSCOPY (3.9 Å) |
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