7ugw
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7ugw]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv], [https://en.wikipedia.org/wiki/Photorhabdus_noenieputensis Photorhabdus noenieputensis] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UGW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UGW FirstGlance]. <br> | <table><tr><td colspan='2'>[[7ugw]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv], [https://en.wikipedia.org/wiki/Photorhabdus_noenieputensis Photorhabdus noenieputensis] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7UGW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UGW FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAR:D-ARGININE'>DAR</scene>, <scene name='pdbligand=DSN:D-SERINE'>DSN</scene>, <scene name='pdbligand=IAS:BETA-L-ASPARTIC+ACID'>IAS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AZ2:3-methyl-D-histidine'>A1AZ2</scene>, <scene name='pdbligand=DAR:D-ARGININE'>DAR</scene>, <scene name='pdbligand=DSN:D-SERINE'>DSN</scene>, <scene name='pdbligand=IAS:BETA-L-ASPARTIC+ACID'>IAS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NLF:(2~{S})-2-formamido-3-(1~{H}-indol-3-yl)propanoic+acid'>NLF</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ugw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ugw OCA], [https://pdbe.org/7ugw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ugw RCSB], [https://www.ebi.ac.uk/pdbsum/7ugw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ugw ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7ugw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ugw OCA], [https://pdbe.org/7ugw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ugw RCSB], [https://www.ebi.ac.uk/pdbsum/7ugw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ugw ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/GYRA_MYCTU 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. | |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == 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. | 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 | + | 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<ref>PMID:35996001</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 7ugw" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7ugw" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Gyrase 3D Structures|Gyrase 3D Structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
M. tuberculosis DNA gyrase cleavage core bound to DNA and evybactin
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