2wks
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 2wks is ON HOLD until Paper Publication Authors: Otero, J.M., Guardado-Calvo, P., Llamas-Saiz, A.L., Prazeres, V.F.V., Tizon, L., Castedo, L., Lamb,...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of Helicobacter pylori Type II Dehydroquinase with a new carbasugar-thiophene inhibitor.== | |
| + | <StructureSection load='2wks' size='340' side='right'caption='[[2wks]], [[Resolution|resolution]] 2.95Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2wks]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Helicobacter_pylori Helicobacter pylori]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WKS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WKS 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]] 2.95Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CB6:(1R,4S,5R)-1,4,5-TRIHYDROXY-3-[(5-METHYL-1-BENZOTHIOPHEN-2-YL)METHOXY]CYCLOHEX-2-ENE-1-CARBOXYLIC+ACID'>CB6</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=2wks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wks OCA], [https://pdbe.org/2wks PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wks RCSB], [https://www.ebi.ac.uk/pdbsum/2wks PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wks ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/AROQ_HELPY AROQ_HELPY] Catalyzes a trans-dehydration via an enolate intermediate (By similarity).[HAMAP-Rule:MF_00169] | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wk/2wks_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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=2wks ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The shikimic acid pathway is essential to many pathogens but absent in mammals. Enzymes in its pathway are therefore appropriate targets for the development of novel antibiotics. Dehydroquinase is the third enzyme of the pathway, catalyzing the reversible dehydratation of 3-dehydroquinic acid to form 3-dehydroshikimic acid. Here we present the synthesis of novel inhibitors with high affinity for Helicobacter pylori type II dehydroquinase and efficient inhibition characteristics. The structure of Helicobacter pylori type II dehydroquinase in complex with the most potent inhibitor shows that the aromatic functional group interacts with the catalytic Tyr22 by pi-stacking, expelling the Arg17 side chain, which is essential for catalysis, from the active site. The structure therefore explains the favorable properties of the inhibitor and will aid in design of improved antibiotics. | ||
| - | + | Synthesis and Biological Evaluation of New Nanomolar Competitive Inhibitors of Helicobacter pylori Type II Dehydroquinase. Structural Details of the Role of the Aromatic Moieties with Essential Residues (double dagger).,Prazeres VF, Tizon L, Otero JM, Guardado-Calvo P, Llamas-Saiz AL, van Raaij MJ, Castedo L, Lamb H, Hawkins AR, Gonzalez-Bello C J Med Chem. 2009 Nov 13. PMID:19911771<ref>PMID:19911771</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 2wks" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| + | *[[Dehydroquinase 3D structures|Dehydroquinase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Helicobacter pylori]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Castedo L]] | ||
| + | [[Category: Gonzalez-Bello C]] | ||
| + | [[Category: Guardado-Calvo P]] | ||
| + | [[Category: Hawkins AR]] | ||
| + | [[Category: Lamb H]] | ||
| + | [[Category: Llamas-Saiz AL]] | ||
| + | [[Category: Otero JM]] | ||
| + | [[Category: Prazeres VFV]] | ||
| + | [[Category: Tizon L]] | ||
| + | [[Category: Van Raaij MJ]] | ||
Current revision
Structure of Helicobacter pylori Type II Dehydroquinase with a new carbasugar-thiophene inhibitor.
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