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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== | ||
<StructureSection load='4ggl' size='340' side='right' caption='[[4ggl]], [[Resolution|resolution]] 1.69Å' scene=''> | <StructureSection load='4ggl' size='340' side='right'caption='[[4ggl]], [[Resolution|resolution]] 1.69Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4ggl]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4ggl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecalis_V583 Enterococcus faecalis V583]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GGL FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CJC:7-({4-[(3R)-3-AMINOPYRROLIDIN-1-YL]-5-CHLORO-6-ETHYL-7H-PYRROLO[2,3-D]PYRIMIDIN-2-YL}SULFANYL)PYRIDO[2,3-B]PYRAZIN-2(1H)-ONE'>CJC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CJC:7-({4-[(3R)-3-AMINOPYRROLIDIN-1-YL]-5-CHLORO-6-ETHYL-7H-PYRROLO[2,3-D]PYRIMIDIN-2-YL}SULFANYL)PYRIDO[2,3-B]PYRAZIN-2(1H)-ONE'>CJC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4ggl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ggl OCA], [https://pdbe.org/4ggl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ggl RCSB], [https://www.ebi.ac.uk/pdbsum/4ggl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ggl ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/GYRB_ENTFA GYRB_ENTFA] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 23: | Line 20: | ||
==See Also== | ==See Also== | ||
*[[Gyrase|Gyrase]] | *[[Gyrase 3D Structures|Gyrase 3D Structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Enterococcus faecalis V583]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Bensen DC]] | ||
[[Category: | [[Category: Creighton CJ]] | ||
[[Category: | [[Category: Tari LW]] | ||
Revision as of 09:55, 26 October 2022
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 activityPyrrolopyrimidine 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
Structural highlights
FunctionPublication Abstract from PubMedThe 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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