1y2f

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(New page: 200px<br /><applet load="1y2f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1y2f, resolution 2.00&Aring;" /> '''Crystal Structure of...)
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[[Image:1y2f.gif|left|200px]]<br /><applet load="1y2f" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1y2f, resolution 2.00&Aring;" />
 
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'''Crystal Structure of ZipA with an inhibitor'''<br />
 
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==Overview==
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==Crystal Structure of ZipA with an inhibitor==
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In this paper, we describe the first prospective application of the, shape-comparison program ROCS (Rapid Overlay of Chemical Structures) to, find new scaffolds for small molecule inhibitors of the ZipA-FtsZ, protein-protein interaction, a proposed antibacterial target. The shape, comparisons are made relative to the crystallographically determined, bioactive conformation of a high-throughput screening (HTS) hit. The use, of ROCS led to the identification of a set of novel, weakly binding, inhibitors with scaffolds presenting synthetic opportunities to further, optimize biological affinity and lacking development issues associated, with the HTS lead. These ROCS-identified scaffolds would have been missed, using other structural similarity approaches such as ISIS 2D fingerprints., X-ray crystallographic analysis of one of the new inhibitors bound to ZipA, reveals that the shape comparison approach very accurately predicted the, binding mode. These experimental results validate this use of ROCS for, chemotype switching or "lead hopping" and suggest that it is of general, interest for lead identification in drug discovery endeavors.
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<StructureSection load='1y2f' size='340' side='right'caption='[[1y2f]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1y2f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y2F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y2F FirstGlance]. <br>
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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]] 2&#8491;</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=WAI:4-{2-[4-(2-AMINOETHYL)PIPERAZIN-1-YL]PYRIDIN-4-YL}-N-(3-CHLORO-4-METHYLPHENYL)PYRIMIDIN-2-AMINE'>WAI</scene></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=1y2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y2f OCA], [https://pdbe.org/1y2f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y2f RCSB], [https://www.ebi.ac.uk/pdbsum/1y2f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y2f ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ZIPA_ECOLI ZIPA_ECOLI] Interacts directly with the cell division protein FtsZ. Probable receptor for the septal ring structure, may anchor it to the inner-membrane.[HAMAP-Rule:MF_00509]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/y2/1y2f_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1y2f ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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In this paper, we describe the first prospective application of the shape-comparison program ROCS (Rapid Overlay of Chemical Structures) to find new scaffolds for small molecule inhibitors of the ZipA-FtsZ protein-protein interaction, a proposed antibacterial target. The shape comparisons are made relative to the crystallographically determined, bioactive conformation of a high-throughput screening (HTS) hit. The use of ROCS led to the identification of a set of novel, weakly binding inhibitors with scaffolds presenting synthetic opportunities to further optimize biological affinity and lacking development issues associated with the HTS lead. These ROCS-identified scaffolds would have been missed using other structural similarity approaches such as ISIS 2D fingerprints. X-ray crystallographic analysis of one of the new inhibitors bound to ZipA reveals that the shape comparison approach very accurately predicted the binding mode. These experimental results validate this use of ROCS for chemotype switching or "lead hopping" and suggest that it is of general interest for lead identification in drug discovery endeavors.
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==About this Structure==
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A shape-based 3-D scaffold hopping method and its application to a bacterial protein-protein interaction.,Rush TS 3rd, Grant JA, Mosyak L, Nicholls A J Med Chem. 2005 Mar 10;48(5):1489-95. PMID:15743191<ref>PMID:15743191</ref>
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1Y2F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with WAI as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Y2F OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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A shape-based 3-D scaffold hopping method and its application to a bacterial protein-protein interaction., Rush TS 3rd, Grant JA, Mosyak L, Nicholls A, J Med Chem. 2005 Mar 10;48(5):1489-95. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15743191 15743191]
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</div>
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[[Category: Escherichia coli]]
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<div class="pdbe-citations 1y2f" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Mosyak, L.]]
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[[Category: Rush, T.S.]]
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[[Category: WAI]]
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[[Category: cell cycle]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 06:31:00 2007''
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==See Also==
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*[[Cell division protein 3D structures|Cell division protein 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Escherichia coli]]
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[[Category: Large Structures]]
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[[Category: Mosyak L]]
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[[Category: Rush TS]]

Current revision

Crystal Structure of ZipA with an inhibitor

PDB ID 1y2f

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