4hy1

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==Pyrrolopyrimidine inhibitors of dna gyrase b and topoisomerase iv, part i: structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity.==
==Pyrrolopyrimidine inhibitors of dna gyrase b and topoisomerase iv, part i: structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity.==
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<StructureSection load='4hy1' size='340' side='right' caption='[[4hy1]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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<StructureSection load='4hy1' size='340' side='right'caption='[[4hy1]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4hy1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Frath Frath]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HY1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HY1 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4hy1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Francisella_tularensis_subsp._holarctica_LVS Francisella tularensis subsp. holarctica LVS]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HY1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HY1 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=19X:6-({4-[(3R)-3-AMINOPYRROLIDIN-1-YL]-5-CHLORO-6-ETHYL-7H-PYRROLO[2,3-D]PYRIMIDIN-2-YL}SULFANYL)-1H-ISOINDOL-1-ONE'>19X</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hxz|4hxz]], [[4gee|4gee]], [[4gfn|4gfn]], [[4ggl|4ggl]], [[4hyp|4hyp]], [[4hym|4hym]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=19X:6-({4-[(3R)-3-AMINOPYRROLIDIN-1-YL]-5-CHLORO-6-ETHYL-7H-PYRROLO[2,3-D]PYRIMIDIN-2-YL}SULFANYL)-1H-ISOINDOL-1-ONE'>19X</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DNA topoisomerase IV subunit B ParE, FTL_1726 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=376619 FRATH])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4hy1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hy1 OCA], [https://pdbe.org/4hy1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hy1 RCSB], [https://www.ebi.ac.uk/pdbsum/4hy1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hy1 ProSAT]</span></td></tr>
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<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>
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<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=4hy1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hy1 OCA], [http://pdbe.org/4hy1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hy1 RCSB], [http://www.ebi.ac.uk/pdbsum/4hy1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hy1 ProSAT]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/PARE_FRATH PARE_FRATH] Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA (PubMed:23352267, PubMed:23294697, PubMed:24386374). Performs the decatenation events required during the replication of a circular DNA molecule.[HAMAP-Rule:MF_00938]<ref>PMID:23352267</ref> <ref>PMID:24386374</ref> <ref>PMID:23294697</ref>
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The bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) are essential enzymes that control the topological state of DNA during replication. The high degree of conservation in the ATP-binding pockets of these enzymes make them appealing targets for broad-spectrum inhibitor development. A pyrrolopyrimidine scaffold was identified from a pharmacophore-based fragment screen with optimization potential. Structural characterization of inhibitor complexes conducted using selected GyrB/ParE orthologs aided in the identification of important steric, dynamic and compositional differences in the ATP-binding pockets of the targets, enabling the design of highly potent pyrrolopyrimidine inhibitors with broad enzymatic spectrum and dual targeting activity.
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Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE). Part I: Structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity.,Tari LW, Trzoss M, Bensen DC, Li X, Chen Z, Lam T, Zhang J, Creighton CJ, Cunningham ML, Kwan B, Stidham M, Shaw KJ, Lightstone FC, Wong SE, Nguyen TB, Nix J, Finn J Bioorg Med Chem Lett. 2012 Dec 5. pii: S0960-894X(12)01475-8. doi:, 10.1016/j.bmcl.2012.11.032. PMID:23352267<ref>PMID:23352267</ref>
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==See Also==
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*[[Topoisomerase 3D structures|Topoisomerase 3D structures]]
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4hy1" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Frath]]
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[[Category: Francisella tularensis subsp. holarctica LVS]]
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[[Category: Bensen, D C]]
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[[Category: Large Structures]]
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[[Category: Creighton, C J]]
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[[Category: Bensen DC]]
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[[Category: Kwan, B]]
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[[Category: Creighton CJ]]
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[[Category: Tari, L W]]
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[[Category: Kwan B]]
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[[Category: Atp-binding]]
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[[Category: Tari LW]]
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[[Category: Atp-binding domain]]
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[[Category: Isomerase-isomerase inhibitor complex]]
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[[Category: Nucleotide-binding]]
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[[Category: Topoisomerase]]
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Current revision

Pyrrolopyrimidine inhibitors of dna gyrase b and topoisomerase iv, part i: structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity.

PDB ID 4hy1

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