4kpf
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Novel fluoroquinolones in complex with topoisomerase IV from S. pneumoniae and E-site G-gate== | |
| + | <StructureSection load='4kpf' size='340' side='right'caption='[[4kpf]], [[Resolution|resolution]] 3.24Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4kpf]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_TIGR4 Streptococcus pneumoniae TIGR4] 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=4KPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KPF 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]] 3.24Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1UV:(3AS,4R)-4-AMINO-13-CYCLOPROPYL-8-FLUORO-10-OXO-3A,4,5,6,10,13-HEXAHYDRO-1H,3H-PYRROLO[2,1 3,4][1,4]OXAZEPINO[5,6-H]QUINOLINE-11-CARBOXYLIC+ACID'>1UV</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=4kpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kpf OCA], [https://pdbe.org/4kpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kpf RCSB], [https://www.ebi.ac.uk/pdbsum/4kpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kpf ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PARC_STRPN PARC_STRPN] Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.<ref>PMID:17375187</ref> <ref>PMID:20596531</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | As part of a programme of synthesizing and investigating the biological properties of new fluoroquinolone antibacterials and their targeting of topoisomerase IV from Streptococcus pneumoniae, we have solved the X-ray structure of the complexes of two new 7,8-bridged fluoroquinolones (with restricted C7 group rotation favouring tight binding) in complex with the topoisomerase IV from S. pneumoniae and an 18-base-pair DNA binding site-the E-site-found by our DNA mapping studies to bind drug strongly in the presence of topoisomerase IV (Leo et al. 2005 J. Biol. Chem. 280, 14 252-14 263, doi:10.1074/jbc.M500156200). Although the degree of antibiotic resistance towards fluoroquinolones is much lower than that of beta-lactams and a range of ribosome-bound antibiotics, there is a pressing need to increase the diversity of members of this successful clinically used class of drugs. The quinolone moiety of the new 7,8-bridged agents ACHN-245 and ACHN-454 binds similarly to that of clinafloxocin, levofloxacin, moxifloxacin and trovofloxacin but the cyclic scaffold offers the possibility of chemical modification to produce interactions with other topoisomerase residues at the active site. | ||
| - | + | Exploring the active site of the Streptococcus pneumoniae topoisomerase IV-DNA cleavage complex with novel 7,8-bridged fluoroquinolones.,Laponogov I, Pan XS, Veselkov DA, Cirz RT, Wagman A, Moser HE, Fisher LM, Sanderson MR Open Biol. 2016 Sep;6(9). pii: rsob.160157. doi: 10.1098/rsob.160157. PMID:27655731<ref>PMID:27655731</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4kpf" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Topoisomerase 3D structures|Topoisomerase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Streptococcus pneumoniae TIGR4]] | ||
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Cirz RT]] | ||
| + | [[Category: Fisher LM]] | ||
| + | [[Category: Laponogov I]] | ||
| + | [[Category: Moser HE]] | ||
| + | [[Category: Pan X-S]] | ||
| + | [[Category: Sanderson MR]] | ||
| + | [[Category: Vesekov DA]] | ||
| + | [[Category: Wagman AS]] | ||
Current revision
Novel fluoroquinolones in complex with topoisomerase IV from S. pneumoniae and E-site G-gate
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