7UGW
M. tuberculosis DNA gyrase cleavage core bound to DNA and evybactin
This is a non-PDB format compatible entry.
Summary for 7UGW
| Entry DOI | 10.2210/pdb7ugw/pdb |
| Related PRD ID | PRD_002540 |
| Descriptor | DNA gyrase subunit A, DNA gyrase subunit B, DNA (46-MER), ... (5 entities in total) |
| Functional Keywords | topoisomerase, inhibitor, natural product, isomerase-antibiotic-dna complex, isomerase/antibiotic/dna |
| Biological source | Mycobacterium tuberculosis H37Rv More |
| Total number of polymer chains | 6 |
| Total formula weight | 183784.17 |
| Authors | Hauk, G.,Imai, Y.,Lewis, K.,Berger, J.M. (deposition date: 2022-03-25, release date: 2022-08-17, Last modification date: 2024-10-02) |
| Primary citation | Imai, Y.,Hauk, G.,Quigley, J.,Liang, L.,Son, S.,Ghiglieri, M.,Gates, M.F.,Morrissette, M.,Shahsavari, N.,Niles, S.,Baldisseri, D.,Honrao, C.,Ma, X.,Guo, J.J.,Berger, J.M.,Lewis, K. Evybactin is a DNA gyrase inhibitor that selectively kills Mycobacterium tuberculosis. Nat.Chem.Biol., 18:1236-1244, 2022 Cited by PubMed Abstract: The antimicrobial resistance crisis requires the introduction of novel antibiotics. The use of conventional broad-spectrum compounds selects for resistance in off-target pathogens and harms the microbiome. This is especially true for Mycobacterium tuberculosis, where treatment requires a 6-month course of antibiotics. Here we show that a novel antimicrobial from Photorhabdus noenieputensis, which we named evybactin, is a potent and selective antibiotic acting against M. tuberculosis. Evybactin targets DNA gyrase and binds to a site overlapping with synthetic thiophene poisons. Given the conserved nature of DNA gyrase, the observed selectivity against M. tuberculosis is puzzling. We found that evybactin is smuggled into the cell by a promiscuous transporter of hydrophilic compounds, BacA. Evybactin is the first, but likely not the only, antimicrobial compound found to employ this unusual mechanism of selectivity. PubMed: 35996001DOI: 10.1038/s41589-022-01102-7 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3 Å) |
Structure validation
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