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| | ==2.65 structure of S.aureus DNA gyrase and artificially nicked DNA== | | ==2.65 structure of S.aureus DNA gyrase and artificially nicked DNA== |
| - | <StructureSection load='5cdr' size='340' side='right' caption='[[5cdr]], [[Resolution|resolution]] 2.65Å' scene=''> | + | <StructureSection load='5cdr' size='340' side='right'caption='[[5cdr]], [[Resolution|resolution]] 2.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5cdr]] is a 7 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CDR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CDR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5cdr]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_N315 Staphylococcus aureus subsp. aureus N315] 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=5CDR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CDR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_topoisomerase_(ATP-hydrolyzing) DNA topoisomerase (ATP-hydrolyzing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.3 5.99.1.3] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5cdr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cdr OCA], [http://pdbe.org/5cdr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cdr RCSB], [http://www.ebi.ac.uk/pdbsum/5cdr PDBsum]</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=5cdr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cdr OCA], [https://pdbe.org/5cdr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cdr RCSB], [https://www.ebi.ac.uk/pdbsum/5cdr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cdr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GYRA_STAAN GYRA_STAAN]] 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.[HAMAP-Rule:MF_01897] [[http://www.uniprot.org/uniprot/GYRB_STAAN GYRB_STAAN]] 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 (By similarity). | + | [https://www.uniprot.org/uniprot/GYRA_STAAN GYRA_STAAN] 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.[HAMAP-Rule:MF_01897] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5cdr" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5cdr" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Gyrase 3D Structures|Gyrase 3D Structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bax, B D]] | + | [[Category: Large Structures]] |
| - | [[Category: Chan, P F]] | + | [[Category: Staphylococcus aureus subsp. aureus N315]] |
| - | [[Category: Srikannathasan, V]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Isomerase]] | + | [[Category: Bax BD]] |
| - | [[Category: Type iia topoisomerase]] | + | [[Category: Chan PF]] |
| | + | [[Category: Srikannathasan V]] |
| Structural highlights
Function
GYRA_STAAN 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.[HAMAP-Rule:MF_01897]
Publication Abstract from PubMed
New antibacterials are needed to tackle antibiotic-resistant bacteria. Type IIA topoisomerases (topo2As), the targets of fluoroquinolones, regulate DNA topology by creating transient double-strand DNA breaks. Here we report the first co-crystal structures of the antibacterial QPT-1 and the anticancer drug etoposide with Staphylococcus aureus DNA gyrase, showing binding at the same sites in the cleaved DNA as the fluoroquinolone moxifloxacin. Unlike moxifloxacin, QPT-1 and etoposide interact with conserved GyrB TOPRIM residues rationalizing why QPT-1 can overcome fluoroquinolone resistance. Our data show etoposide's antibacterial activity is due to DNA gyrase inhibition and suggests other anticancer agents act similarly. Analysis of multiple DNA gyrase co-crystal structures, including asymmetric cleavage complexes, led to a 'pair of swing-doors' hypothesis in which the movement of one DNA segment regulates cleavage and religation of the second DNA duplex. This mechanism can explain QPT-1's bacterial specificity. Structure-based strategies for developing topo2A antibacterials are suggested.
Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin.,Chan PF, Srikannathasan V, Huang J, Cui H, Fosberry AP, Gu M, Hann MM, Hibbs M, Homes P, Ingraham K, Pizzollo J, Shen C, Shillings AJ, Spitzfaden CE, Tanner R, Theobald AJ, Stavenger RA, Bax BD, Gwynn MN Nat Commun. 2015 Dec 7;6:10048. doi: 10.1038/ncomms10048. PMID:26640131[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chan PF, Srikannathasan V, Huang J, Cui H, Fosberry AP, Gu M, Hann MM, Hibbs M, Homes P, Ingraham K, Pizzollo J, Shen C, Shillings AJ, Spitzfaden CE, Tanner R, Theobald AJ, Stavenger RA, Bax BD, Gwynn MN. Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin. Nat Commun. 2015 Dec 7;6:10048. doi: 10.1038/ncomms10048. PMID:26640131 doi:http://dx.doi.org/10.1038/ncomms10048
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