6YFY

Solid-state NMR structure of the D-Arg4,L10-teixobactin - Lipid II complex in lipid bilayers.

6YFY の概要

• エントリーDOI: 10.2210/pdb6yfy/pdb
• NMR情報: BMRB: 50202
• 関連するBIRD辞書のPRD_ID: PRD_002267 PRD_002268
• 分子名称: D-Arg4,Leu10-Teixobactin, Lipid II, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-N-acetyl-alpha-muramic acid, ... (5 entities in total)
• 機能のキーワード: teixobactin lipid ii complex antimicrobial peptide, antibiotic
• 由来する生物種: Staphylococcus simulans; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 10611.59

構造登録者

Weingarth, M.H.,Shukla, R. (登録日: 2020-03-26, 公開日: 2020-06-10, 最終更新日: 2024-08-07)

主引用文献

Shukla, R.,Medeiros-Silva, J.,Parmar, A.,Vermeulen, B.J.A.,Das, S.,Paioni, A.L.,Jekhmane, S.,Lorent, J.,Bonvin, A.M.J.J.,Baldus, M.,Lelli, M.,Veldhuizen, E.J.A.,Breukink, E.,Singh, I.,Weingarth, M.
Mode of action of teixobactins in cellular membranes.
Nat Commun, 11:2848-2848, 2020

PubMed Abstract: The natural antibiotic teixobactin kills pathogenic bacteria without detectable resistance. The difficult synthesis and unfavourable solubility of teixobactin require modifications, yet insufficient knowledge on its binding mode impedes the hunt for superior analogues. Thus far, teixobactins are assumed to kill bacteria by binding to cognate cell wall precursors (Lipid II and III). Here we present the binding mode of teixobactins in cellular membranes using solid-state NMR, microscopy, and affinity assays. We solve the structure of the complex formed by an improved teixobactin-analogue and Lipid II and reveal how teixobactins recognize a broad spectrum of targets. Unexpectedly, we find that teixobactins only weakly bind to Lipid II in cellular membranes, implying the direct interaction with cell wall precursors is not the sole killing mechanism. Our data suggest an additional mechanism affords the excellent activity of teixobactins, which can block the cell wall biosynthesis by capturing precursors in massive clusters on membranes.

PubMed: 32503964
DOI: 10.1038/s41467-020-16600-2

実験手法

SOLID-STATE NMR