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| | <StructureSection load='2wks' size='340' side='right'caption='[[2wks]], [[Resolution|resolution]] 2.95Å' scene=''> | | <StructureSection load='2wks' size='340' side='right'caption='[[2wks]], [[Resolution|resolution]] 2.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2wks]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_43504 Atcc 43504]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WKS FirstGlance]. <br> | + | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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> | + | </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2c57|2c57]], [[2c4v|2c4v]], [[1j2y|1j2y]], [[2c4w|2c4w]]</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/3-dehydroquinate_dehydratase 3-dehydroquinate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.10 4.2.1.10] </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=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> |
| - | <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=2wks FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wks OCA], [http://pdbe.org/2wks PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wks RCSB], [http://www.ebi.ac.uk/pdbsum/2wks PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wks ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AROQ_HELPY AROQ_HELPY]] Catalyzes a trans-dehydration via an enolate intermediate (By similarity).[HAMAP-Rule:MF_00169] | + | [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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 3-dehydroquinate dehydratase]] | + | [[Category: Helicobacter pylori]] |
| - | [[Category: Atcc 43504]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Castedo, L]] | + | [[Category: Castedo L]] |
| - | [[Category: Gonzalez-Bello, C]] | + | [[Category: Gonzalez-Bello C]] |
| - | [[Category: Guardado-Calvo, P]] | + | [[Category: Guardado-Calvo P]] |
| - | [[Category: Hawkins, A R]] | + | [[Category: Hawkins AR]] |
| - | [[Category: Lamb, H]] | + | [[Category: Lamb H]] |
| - | [[Category: Llamas-Saiz, A L]] | + | [[Category: Llamas-Saiz AL]] |
| - | [[Category: Otero, J M]] | + | [[Category: Otero JM]] |
| - | [[Category: Prazeres, V F.V]] | + | [[Category: Prazeres VFV]] |
| - | [[Category: Raaij, M J.van]]
| + | [[Category: Tizon L]] |
| - | [[Category: Tizon, L]] | + | [[Category: Van Raaij MJ]] |
| - | [[Category: Aromatic amino acid biosynthesis]] | + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Shikimic acid pathway]]
| + | |
| Structural highlights
Function
AROQ_HELPY Catalyzes a trans-dehydration via an enolate intermediate (By similarity).[HAMAP-Rule:MF_00169]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Prazeres VF, Tizon L, Otero JM, Guardado-Calvo P, Llamas-Saiz AL, van Raaij MJ, Castedo L, Lamb H, Hawkins AR, Gonzalez-Bello C. 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). J Med Chem. 2009 Nov 13. PMID:19911771 doi:10.1021/jm9010466
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