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| | <StructureSection load='1we2' size='340' side='right'caption='[[1we2]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='1we2' size='340' side='right'caption='[[1we2]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1we2]] is a 1 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=1WE2 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1WE2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1we2]] is a 1 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=1WE2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WE2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DHK:3-DEHYDROSHIKIMATE'>DHK</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1l4y|1l4y]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DHK:3-DEHYDROSHIKIMATE'>DHK</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AROK ([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=1we2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1we2 OCA], [https://pdbe.org/1we2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1we2 RCSB], [https://www.ebi.ac.uk/pdbsum/1we2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1we2 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/Shikimate_kinase Shikimate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.71 2.7.1.71] </span></td></tr> | + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1we2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1we2 OCA], [http://pdbe.org/1we2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1we2 RCSB], [http://www.ebi.ac.uk/pdbsum/1we2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1we2 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AROK_MYCTU AROK_MYCTU]] Catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid using ATP as a cosubstrate.<ref>PMID:11483005</ref> <ref>PMID:17020768</ref> | + | [https://www.uniprot.org/uniprot/AROK_MYCTU AROK_MYCTU] Catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid using ATP as a cosubstrate.<ref>PMID:11483005</ref> <ref>PMID:17020768</ref> |
| | == 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== |
| - | *[[Shikimate kinase|Shikimate kinase]] | + | *[[Shikimate kinase 3D structures|Shikimate kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Shikimate kinase]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Azevedo, W F.de]]
| + | [[Category: Basso LA]] |
| - | [[Category: Basso, L A]] | + | [[Category: Canduri F]] |
| - | [[Category: Canduri, F]] | + | [[Category: Dias MV]] |
| - | [[Category: Dias, M V]] | + | [[Category: Palma MS]] |
| - | [[Category: Oliveira, J S.de]]
| + | [[Category: Pereira JH]] |
| - | [[Category: Palma, M S]] | + | [[Category: Santos DS]] |
| - | [[Category: Pereira, J H]] | + | [[Category: De Azevedo Jr WF]] |
| - | [[Category: Santos, D S]] | + | [[Category: De Oliveira JS]] |
| - | [[Category: Drug design]] | + | |
| - | [[Category: Shikimate pathway]] | + | |
| - | [[Category: Synchrotron]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
AROK_MYCTU Catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid using ATP as a cosubstrate.[1] [2]
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
Tuberculosis made a resurgence in the mid-1980s and now kills approximately 3 million people a year. The re-emergence of tuberculosis as a public health threat, the high susceptibility of HIV-infected persons and the proliferation of multi-drug-resistant strains have created a need to develop new drugs. Shikimate kinase and other enzymes in the shikimate pathway are attractive targets for development of non-toxic antimicrobial agents, herbicides and anti-parasitic drugs, because the pathway is essential in these species whereas it is absent from mammals. The crystal structure of shikimate kinase from Mycobacterium tuberculosis (MtSK) complexed with MgADP and shikimic acid (shikimate) has been determined at 2.3 A resolution, clearly revealing the amino-acid residues involved in shikimate binding. This is the first three-dimensional structure of shikimate kinase complexed with shikimate. In MtSK, the Glu61 residue that is strictly conserved in shikimate kinases forms a hydrogen bond and salt bridge with Arg58 and assists in positioning the guanidinium group of Arg58 for shikimate binding. The carboxyl group of shikimate interacts with Arg58, Gly81 and Arg136 and the hydroxyl groups interact with Asp34 and Gly80. The crystal structure of MtSK-MgADP-shikimate will provide crucial information for the elucidation of the mechanism of the shikimate kinase-catalyzed reaction and for the development of a new generation of drugs against tuberculosis.
Structure of shikimate kinase from Mycobacterium tuberculosis reveals the binding of shikimic acid.,Pereira JH, de Oliveira JS, Canduri F, Dias MV, Palma MS, Basso LA, Santos DS, de Azevedo WF Jr Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 2):2310-9. Epub, 2004 Nov 26. PMID:15583379[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Oliveira JS, Pinto CA, Basso LA, Santos DS. Cloning and overexpression in soluble form of functional shikimate kinase and 5-enolpyruvylshikimate 3-phosphate synthase enzymes from Mycobacterium tuberculosis. Protein Expr Purif. 2001 Aug;22(3):430-5. PMID:11483005 doi:10.1006/prep.2001.1457
- ↑ Hartmann MD, Bourenkov GP, Oberschall A, Strizhov N, Bartunik HD. Mechanism of phosphoryl transfer catalyzed by shikimate kinase from Mycobacterium tuberculosis. J Mol Biol. 2006 Dec 1;364(3):411-23. Epub 2006 Sep 5. PMID:17020768 doi:10.1016/j.jmb.2006.09.001
- ↑ Pereira JH, de Oliveira JS, Canduri F, Dias MV, Palma MS, Basso LA, Santos DS, de Azevedo WF Jr. Structure of shikimate kinase from Mycobacterium tuberculosis reveals the binding of shikimic acid. Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 2):2310-9. Epub, 2004 Nov 26. PMID:15583379 doi:10.1107/S090744490402517X
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