6YFY
Solid-state NMR structure of the D-Arg4,L10-teixobactin - Lipid II complex in lipid bilayers.
Summary for 6YFY
| Entry DOI | 10.2210/pdb6yfy/pdb |
| NMR Information | BMRB: 50202 |
| Related PRD ID | PRD_002267 PRD_002268 |
| Descriptor | D-Arg4,Leu10-Teixobactin, Lipid II, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-N-acetyl-alpha-muramic acid, ... (5 entities in total) |
| Functional Keywords | teixobactin lipid ii complex antimicrobial peptide, antibiotic |
| Biological source | Staphylococcus simulans More |
| Total number of polymer chains | 8 |
| Total formula weight | 10611.59 |
| Authors | Weingarth, M.H.,Shukla, R. (deposition date: 2020-03-26, release date: 2020-06-10, Last modification date: 2024-08-07) |
| Primary citation | 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 Cited by 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: 32503964DOI: 10.1038/s41467-020-16600-2 PDB entries with the same primary citation |
| Experimental method | SOLID-STATE NMR |
Structure validation
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