View source for 5bs8


==Crystal structure of a topoisomerase II complex==
<StructureSection load='5bs8' size='340' side='right'caption='[[5bs8]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5bs8]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv] 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=5BS8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BS8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.399&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MFX:1-CYCLOPROPYL-6-FLUORO-8-METHOXY-7-[(4AS,7AS)-OCTAHYDRO-6H-PYRROLO[3,4-B]PYRIDIN-6-YL]-4-OXO-1,4-DIHYDROQUINOLINE-3-CARBOXYLIC+ACID'>MFX</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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=5bs8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bs8 OCA], [https://pdbe.org/5bs8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bs8 RCSB], [https://www.ebi.ac.uk/pdbsum/5bs8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bs8 ProSAT]</span></td></tr>
</table>
== 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.
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== Publication Abstract from PubMed ==
Mycobacterium tuberculosis (Mtb) infects one-third of the world's population and in 2013 accounted for 1.5 million deaths. Fluoroquinolone antibacterials, which target DNA gyrase, are critical agents used to halt the progression from multidrug-resistant tuberculosis to extensively resistant disease; however, fluoroquinolone resistance is emerging and new ways to bypass resistance are required. To better explain known differences in fluoroquinolone action, the crystal structures of the WT Mtb DNA gyrase cleavage core and a fluoroquinolone-sensitized mutant were determined in complex with DNA and five fluoroquinolones. The structures, ranging from 2.4- to 2.6-A resolution, show that the intrinsically low susceptibility of Mtb to fluoroquinolones correlates with a reduction in contacts to the water shell of an associated magnesium ion, which bridges fluoroquinolone-gyrase interactions. Surprisingly, the structural data revealed few differences in fluoroquinolone-enzyme contacts from drugs that have very different activities against Mtb. By contrast, a stability assay using purified components showed a clear relationship between ternary complex reversibility and inhibitory activities reported with cultured cells. Collectively, our data indicate that the stability of fluoroquinolone/DNA interactions is a major determinant of fluoroquinolone activity and that moieties that have been appended to the C7 position of different quinolone scaffolds do not take advantage of specific contacts that might be made with the enzyme. These concepts point to new approaches for developing quinolone-class compounds that have increased potency against Mtb and the ability to overcome resistance.

Crystal structure and stability of gyrase-fluoroquinolone cleaved complexes from Mycobacterium tuberculosis.,Blower TR, Williamson BH, Kerns RJ, Berger JM Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1706-13. doi:, 10.1073/pnas.1525047113. Epub 2016 Jan 20. PMID:26792525<ref>PMID:26792525</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5bs8" style="background-color:#fffaf0;"></div>

==See Also==
*[[Gyrase 3D Structures|Gyrase 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Synthetic construct]]
[[Category: Berger JM]]
[[Category: Blower TR]]
[[Category: Kerns RJ]]
[[Category: Williamson BH]]