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| | <StructureSection load='5iwi' size='340' side='right'caption='[[5iwi]], [[Resolution|resolution]] 1.98Å' scene=''> | | <StructureSection load='5iwi' size='340' side='right'caption='[[5iwi]], [[Resolution|resolution]] 1.98Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5iwi]] is a 7 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885] and [http://en.wikipedia.org/wiki/Staan Staan]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IWI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5IWI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5iwi]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus], [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=5IWI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IWI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6EJ:(1R)-1-[(4-{[(6,7-DIHYDRO[1,4]DIOXINO[2,3-C]PYRIDAZIN-3-YL)METHYL]AMINO}PIPERIDIN-1-YL)METHYL]-9-FLUORO-1,2-DIHYDRO-4H-PYRROLO[3,2,1-IJ]QUINOLIN-4-ONE'>6EJ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <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]] 1.98Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gyrB, SA0005 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885]), gyrA, SA0006 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158879 STAAN])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6EJ:(1R)-1-[(4-{[(6,7-DIHYDRO[1,4]DIOXINO[2,3-C]PYRIDAZIN-3-YL)METHYL]AMINO}PIPERIDIN-1-YL)METHYL]-9-FLUORO-1,2-DIHYDRO-4H-PYRROLO[3,2,1-IJ]QUINOLIN-4-ONE'>6EJ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5iwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iwi OCA], [https://pdbe.org/5iwi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iwi RCSB], [https://www.ebi.ac.uk/pdbsum/5iwi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iwi ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5iwi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iwi OCA], [http://pdbe.org/5iwi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iwi RCSB], [http://www.ebi.ac.uk/pdbsum/5iwi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5iwi ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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). [[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] | + | [https://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). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Staan]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Bax, B D]] | + | [[Category: Staphylococcus aureus subsp. aureus N315]] |
| - | [[Category: Miles, T J]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Antibacterial]] | + | [[Category: Bax BD]] |
| - | [[Category: Fusion protein]] | + | [[Category: Miles TJ]] |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Type iia topoisomerase]]
| + | |
| Structural highlights
5iwi is a 7 chain structure with sequence from Staphylococcus aureus, Staphylococcus aureus subsp. aureus N315 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.98Å |
| Ligands: | , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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).
Publication Abstract from PubMed
During the course of our research on the lead optimisation of the NBTI (Novel Bacterial Type II Topoisomerase Inhibitors) class of antibacterials, we discovered a series of tricyclic compounds that showed good Gram-positive and Gram-negative potency. Herein we will discuss the various subunits that were investigated in this series and report advanced studies on compound 1 (GSK945237) which demonstrates good PK and in vivo efficacy properties.
Novel tricyclics (e.g., GSK945237) as potent inhibitors of bacterial type IIA topoisomerases.,Miles TJ, Hennessy AJ, Bax B, Brooks G, Brown BS, Brown P, Cailleau N, Chen D, Dabbs S, Davies DT, Esken JM, Giordano I, Hoover JL, Jones GE, Kusalakumari Sukmar SK, Markwell RE, Minthorn EA, Rittenhouse S, Gwynn MN, Pearson ND Bioorg Med Chem Lett. 2016 Mar 31. pii: S0960-894X(16)30338-9. doi:, 10.1016/j.bmcl.2016.03.106. PMID:27055939[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Miles TJ, Hennessy AJ, Bax B, Brooks G, Brown BS, Brown P, Cailleau N, Chen D, Dabbs S, Davies DT, Esken JM, Giordano I, Hoover JL, Jones GE, Kusalakumari Sukmar SK, Markwell RE, Minthorn EA, Rittenhouse S, Gwynn MN, Pearson ND. Novel tricyclics (e.g., GSK945237) as potent inhibitors of bacterial type IIA topoisomerases. Bioorg Med Chem Lett. 2016 Mar 31. pii: S0960-894X(16)30338-9. doi:, 10.1016/j.bmcl.2016.03.106. PMID:27055939 doi:http://dx.doi.org/10.1016/j.bmcl.2016.03.106
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