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| | ==Type II dehydroquinase from Mycobacterium Tuberculosis complexed with 3-dehydroshikimate== | | ==Type II dehydroquinase from Mycobacterium Tuberculosis complexed with 3-dehydroshikimate== |
| - | <StructureSection load='3n59' size='340' side='right' caption='[[3n59]], [[Resolution|resolution]] 2.52Å' scene=''> | + | <StructureSection load='3n59' size='340' side='right'caption='[[3n59]], [[Resolution|resolution]] 2.52Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3n59]] is a 24 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N59 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N59 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3n59]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N59 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N59 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3DS:(4S,5R)-4,5-DIHYDROXY-3-OXOCYCLOHEX-1-ENE-1-CARBOXYLIC+ACID'>3DS</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.52Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1h0r|1h0r]], [[2dhq|2dhq]], [[1h0s|1h0s]], [[1h05|1h05]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3DS:(4S,5R)-4,5-DIHYDROXY-3-OXOCYCLOHEX-1-ENE-1-CARBOXYLIC+ACID'>3DS</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">aroD, aroQ, MT2612, MTCY159.19, Rv2537c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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=3n59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n59 OCA], [https://pdbe.org/3n59 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n59 RCSB], [https://www.ebi.ac.uk/pdbsum/3n59 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n59 ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3n59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n59 OCA], [http://pdbe.org/3n59 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3n59 RCSB], [http://www.ebi.ac.uk/pdbsum/3n59 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3n59 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AROQ_MYCTU AROQ_MYCTU]] Catalyzes a trans-dehydration via an enolate intermediate (By similarity).[HAMAP-Rule:MF_00169] | + | [https://www.uniprot.org/uniprot/AROQ_MYCTU AROQ_MYCTU] 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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| | ==See Also== | | ==See Also== |
| - | *[[Dehydroquinase|Dehydroquinase]] | + | *[[Dehydroquinase 3D structures|Dehydroquinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 3-dehydroquinate dehydratase]] | + | [[Category: Large Structures]] |
| - | [[Category: Abell, C]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Blundell, T L]] | + | [[Category: Abell C]] |
| - | [[Category: Bromfield, K M]] | + | [[Category: Blundell TL]] |
| - | [[Category: Ciulli, A]] | + | [[Category: Bromfield KM]] |
| - | [[Category: Dias, M V.B]] | + | [[Category: Ciulli A]] |
| - | [[Category: Howard, N I]] | + | [[Category: Dias MVB]] |
| - | [[Category: Palaninathan, S K]] | + | [[Category: Howard NI]] |
| - | [[Category: Payne, R]] | + | [[Category: Palaninathan SK]] |
| - | [[Category: Sacchettini, J C]] | + | [[Category: Payne R]] |
| - | [[Category: Snee, W C]] | + | [[Category: Sacchettini JC]] |
| - | [[Category: Structural genomic]]
| + | [[Category: Snee WC]] |
| - | [[Category: 3-dehydroshikimate]]
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| - | [[Category: Aromatic amino acid biosynthesis]]
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| - | [[Category: Dehydratase]]
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| - | [[Category: Drug target]]
| + | |
| - | [[Category: Lyase]]
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| - | [[Category: Shikimate pathway]]
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| - | [[Category: Tbsgc]]
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| - | [[Category: Tuberculosis]]
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| Structural highlights
Function
AROQ_MYCTU 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 shikimate pathway is essential in Mycobacterium tuberculosis and its absence in humans makes the enzymes of this pathway potential drug targets. In this report, we provide structural insights into ligand and inhibitor binding to 3-dehydroquinate dehydratase (dehydroquinase) from Mycobacterium tuberculosis (MtDHQase), the third enzyme of the shikimate pathway. The enzyme has been crystallized in complex with its reaction product, 3-dehydroshikimate, and with six different competitive inhibitors. The inhibitor 2,3-anhydroquinate mimics the flattened enol/enolate reaction intermediate and serves as an anchor molecule for four of the inhibitors investigated. MtDHQase also forms a complex with citrazinic acid, a planar analog of the reaction product. The structure of MtDHQase in complex with a 2,3-anhydroquinate moiety attached to a biaryl group shows that this group extends to an active site subpocket inducing significant structural re-arrangement. The flexible extensions of inhibitors designed to form pi-stacking interactions with the catalytic Tyr24 residue have been investigated. The high resolution crystal structures of the MtDHQase complexes provide structural evidence for the role of the loop residues 19-24 in MtDHQase ligand binding and catalytic mechanism and provide rationale for the design and efficacy of inhibitors.
Structural investigation of inhibitor designs targeting 3-dehydroquinate dehydratase from the shikimate pathway of Mycobacterium tuberculosis.,Dias MV, Snee WC, Bromfield KM, Payne R, Palaninathan SK, Ciulli A, Howard NI, Abell C, Sacchettini JC, Blundell TL Biochem J. 2011 Mar 17. PMID:21410435[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dias MV, Snee WC, Bromfield KM, Payne R, Palaninathan SK, Ciulli A, Howard NI, Abell C, Sacchettini JC, Blundell TL. Structural investigation of inhibitor designs targeting 3-dehydroquinate dehydratase from the shikimate pathway of Mycobacterium tuberculosis. Biochem J. 2011 Mar 17. PMID:21410435 doi:10.1042/BJ20110002
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