7ugw
From Proteopedia
M. tuberculosis DNA gyrase cleavage core bound to DNA and evybactin
Structural highlights
FunctionGYRA_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 PubMedThe 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 Nov;18(11):1236-1244. doi: 10.1038/s41589-022-01102-7. Epub , 2022 Aug 22. PMID:35996001[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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