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4lpb
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4lpb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_R6 Streptococcus pneumoniae R6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LPB FirstGlance]. <br> | <table><tr><td colspan='2'>[[4lpb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_R6 Streptococcus pneumoniae R6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LPB FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1YP:1-ETHYL-3-{5-(5-OXO-4,5-DIHYDRO-1,3,4-OXADIAZOL-2-YL)-4-[4-(TRIFLUOROMETHYL)-1,3-THIAZOL-2-YL]-3,3-BIPYRIDIN-6-YL}UREA'>1YP</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]] 1.75Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1YP:1-ETHYL-3-{5-(5-OXO-4,5-DIHYDRO-1,3,4-OXADIAZOL-2-YL)-4-[4-(TRIFLUOROMETHYL)-1,3-THIAZOL-2-YL]-3,3-BIPYRIDIN-6-YL}UREA'>1YP</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=4lpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lpb OCA], [https://pdbe.org/4lpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lpb RCSB], [https://www.ebi.ac.uk/pdbsum/4lpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lpb ProSAT]</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=4lpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lpb OCA], [https://pdbe.org/4lpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lpb RCSB], [https://www.ebi.ac.uk/pdbsum/4lpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lpb ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/Q8DQB5_STRR6 Q8DQB5_STRR6] | [https://www.uniprot.org/uniprot/Q8DQB5_STRR6 Q8DQB5_STRR6] | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | The discovery and optimization of a new class of bacterial topoisomerase (DNA gyrase and topoisomerase IV) inhibitors binding in the ATP domain are described. A fragment molecule, 1-ethyl-3-(2-pyridyl)urea, provided sufficiently potent enzyme inhibition (32 muM) to prompt further analogue work. Acids and acid isosteres were incorporated at the 5-pyridyl position of this fragment, bridging to a key asparagine residue, improving enzyme inhibition, and leading to measurable antibacterial activity. A CF3-thiazole substituent at the 4-pyridyl position improved inhibitory potency due to a favorable lipophilic interaction. Promising antibacterial activity was seen versus the Gram-positive pathogens Staphylococcus aureus and Streptococcus pneumoniae and the Gram-negative pathogens Haemophilus influenzae and Moraxella catarrhalis . Precursor metabolite incorporation and mutant analysis studies support the mode-of-action, blockage of DNA synthesis by dual target topoisomerase inhibition. Compound 35 was efficacious in a mouse S. aureus disease model, where a 4.5-log reduction in colony forming units versus control was demonstrated. | ||
| - | |||
| - | Fragment-to-Hit-to-Lead Discovery of a Novel Pyridylurea Scaffold of ATP Competitive Dual Targeting Type II Topoisomerase Inhibiting Antibacterial Agents.,Basarab GS, Manchester JI, Bist S, Boriack-Sjodin PA, Dangel B, Illingworth R, Sherer BA, Sriram S, Uria-Nickelsen M, Eakin AE J Med Chem. 2013 Oct 29. PMID:24098982<ref>PMID:24098982</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4lpb" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Topoisomerase 3D structures|Topoisomerase 3D structures]] | *[[Topoisomerase 3D structures|Topoisomerase 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of a topoisomerase ATPase inhibitor
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