| Structural highlights
7ugw is a 6 chain structure with sequence from Mycobacterium tuberculosis H37Rv, Photorhabdus noenieputensis and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | DAR, DSN, IAS, MG, MHS, NLF |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
GYRA_MYCTU DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.
Publication Abstract from PubMed
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.
Evybactin is a DNA gyrase inhibitor that selectively kills Mycobacterium tuberculosis.,Imai Y, Hauk G, Quigley J, Liang L, Son S, Ghiglieri M, Gates MF, Morrissette M, Shahsavari N, Niles S, Baldisseri D, Honrao C, Ma X, Guo JJ, Berger JM, Lewis K Nat Chem Biol. 2022 Aug 22. pii: 10.1038/s41589-022-01102-7. doi:, 10.1038/s41589-022-01102-7. PMID:35996001[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Imai Y, Hauk G, Quigley J, Liang L, Son S, Ghiglieri M, Gates MF, Morrissette M, Shahsavari N, Niles S, Baldisseri D, Honrao C, Ma X, Guo JJ, Berger JM, Lewis K. Evybactin is a DNA gyrase inhibitor that selectively kills Mycobacterium tuberculosis. Nat Chem Biol. 2022 Aug 22. pii: 10.1038/s41589-022-01102-7. doi:, 10.1038/s41589-022-01102-7. PMID:35996001 doi:https://dx.doi.org/10.1038/s41589-022-01102-7
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