9I95
Cryo-EM structure of Shigella flexneri LptDE bound by a Bicyclic peptide molecule (Compound 4)
This is a non-PDB format compatible entry.
Summary for 9I95
| Entry DOI | 10.2210/pdb9i95/pdb |
| EMDB information | 52752 |
| Descriptor | LPS-assembly protein LptD, LPS-assembly lipoprotein LptE, Bicycle Peptide Binder - Compound 4, ... (5 entities in total) |
| Functional Keywords | outer membrane protein, lipid transport, membrane protein |
| Biological source | Shigella flexneri More |
| Total number of polymer chains | 3 |
| Total formula weight | 111001.79 |
| Authors | Allyjaun, S.,Newman, H.,Dunbar, E.,Hardwick, S.W.,Chirgadze, D.Y.,van den Berg, B.,Hubbard, J. (deposition date: 2025-02-06, release date: 2025-10-15, Last modification date: 2025-11-05) |
| Primary citation | Allyjaun, S.,Dunbar, E.,Hardwick, S.W.,Newell, S.,Holding, F.,Rowland, C.E.,St Denis, M.A.,Pellegrino, S.,Arruda Bezerra, G.,Bournakas, N.,Chirgadze, D.Y.,Cooper, L.,Paris, G.,Lewis, N.,Brown, P.,Skynner, M.J.,Dawson, M.J.,Beswick, P.,Hubbard, J.,van den Berg, B.,Newman, H. High-Throughput Identification and Characterization of LptDE-Binding Bicycle Peptides Using Phage Display and Cryo-EM. J.Med.Chem., 68:21144-21155, 2025 Cited by PubMed Abstract: The lipopolysaccharide (LPS) transport (Lpt) system in Gram-negative bacteria maintains the integrity of the asymmetric bacterial outer membrane (OM). LPS biogenesis systems are essential in most Gram-negative bacteria, with LptDE responsible for the delivery of LPS to the outer leaflet of the OM. As an externally accessible, essential protein, LptDE offers a promising target for inhibitor development without the need for cellular penetration. However, there are no direct inhibitors of LptDE, and drug discovery is made challenging since it is a membrane target without a conventional active site. Here, the bicycle phage display platform was used in combination with cryogenic-electron microscopy (cryo-EM) and surface plasmon resonance to identify and map bicyclic peptide binders to LptDE (SfLptDE). Four distinct epitopes with unique bicycle molecule binding motifs were identified across the SfLptD β-barrel. This method represents a streamlined workflow for the identification and prioritization of hit molecules against LptDE. PubMed: 41048016DOI: 10.1021/acs.jmedchem.5c00307 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.35 Å) |
Structure validation
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