7R1W
E. coli BAM complex (BamABCDE) bound to dynobactin A
Summary for 7R1W
| Entry DOI | 10.2210/pdb7r1w/pdb |
| EMDB information | 14242 |
| Related PRD ID | PRD_002404 |
| Descriptor | Outer membrane protein assembly factor BamA, Outer membrane protein assembly factor BamB, Outer membrane protein assembly factor BamC, ... (6 entities in total) |
| Functional Keywords | beta-barrel, outer membrane, protein insertion, protein folding, protein maturation, antibiotic, natural product, cyclized peptide, membrane protein |
| Biological source | Escherichia coli K-12 More |
| Total number of polymer chains | 6 |
| Total formula weight | 212845.49 |
| Authors | Jakob, R.P.,Hiller, S.,Maier, T. (deposition date: 2022-02-03, release date: 2022-09-28, Last modification date: 2025-07-02) |
| Primary citation | Miller, R.D.,Iinishi, A.,Modaresi, S.M.,Yoo, B.K.,Curtis, T.D.,Lariviere, P.J.,Liang, L.,Son, S.,Nicolau, S.,Bargabos, R.,Morrissette, M.,Gates, M.F.,Pitt, N.,Jakob, R.P.,Rath, P.,Maier, T.,Malyutin, A.G.,Kaiser, J.T.,Niles, S.,Karavas, B.,Ghiglieri, M.,Bowman, S.E.J.,Rees, D.C.,Hiller, S.,Lewis, K. Computational identification of a systemic antibiotic for gram-negative bacteria. Nat Microbiol, 7:1661-1672, 2022 Cited by PubMed Abstract: Discovery of antibiotics acting against Gram-negative species is uniquely challenging due to their restrictive penetration barrier. BamA, which inserts proteins into the outer membrane, is an attractive target due to its surface location. Darobactins produced by Photorhabdus, a nematode gut microbiome symbiont, target BamA. We reasoned that a computational search for genes only distantly related to the darobactin operon may lead to novel compounds. Following this clue, we identified dynobactin A, a novel peptide antibiotic from Photorhabdus australis containing two unlinked rings. Dynobactin is structurally unrelated to darobactins, but also targets BamA. Based on a BamA-dynobactin co-crystal structure and a BAM-complex-dynobactin cryo-EM structure, we show that dynobactin binds to the BamA lateral gate, uniquely protruding into its β-barrel lumen. Dynobactin showed efficacy in a mouse systemic Escherichia coli infection. This study demonstrates the utility of computational approaches to antibiotic discovery and suggests that dynobactin is a promising lead for drug development. PubMed: 36163500DOI: 10.1038/s41564-022-01227-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
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