|
|
| (3 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal Structure of M. tuberculosis MenD bound to ThDP and Mn2+== | | ==Crystal Structure of M. tuberculosis MenD bound to ThDP and Mn2+== |
| - | <StructureSection load='5esd' size='340' side='right' caption='[[5esd]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='5esd' size='340' side='right'caption='[[5esd]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5esd]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ESD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ESD FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5esd]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ESD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ESD FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TDP:THIAMIN+DIPHOSPHATE'>TDP</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]] 2.25Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5erx|5erx]], [[5ery|5ery]], [[5esu|5esu]], [[5eso|5eso]], [[5ess|5ess]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TPP:THIAMINE+DIPHOSPHATE'>TPP</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid_synthase 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.2.1.9 2.2.1.9] </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=5esd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5esd OCA], [https://pdbe.org/5esd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5esd RCSB], [https://www.ebi.ac.uk/pdbsum/5esd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5esd 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=5esd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5esd OCA], [http://pdbe.org/5esd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5esd RCSB], [http://www.ebi.ac.uk/pdbsum/5esd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5esd ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MEND_MYCTU MEND_MYCTU]] Catalyzes the thiamine diphosphate-dependent decarboxylation of 2-oxoglutarate and the subsequent addition of the resulting succinic semialdehyde-thiamine pyrophosphate anion to isochorismate to yield 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC). | + | [https://www.uniprot.org/uniprot/MEND_MYCTU MEND_MYCTU] Catalyzes the thiamine diphosphate-dependent decarboxylation of 2-oxoglutarate and the subsequent addition of the resulting succinic semialdehyde-thiamine pyrophosphate anion to isochorismate to yield 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC). |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Menaquinone (MQ) is an essential component of the respiratory chains of many pathogenic organisms, including Mycobacterium tuberculosis (Mtb). The first committed step in MQ biosynthesis is catalyzed by 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexadiene-1-carboxylate synthase (MenD), a thiamin diphosphate (ThDP)-dependent enzyme. Catalysis proceeds through two covalent intermediates as the substrates 2-oxoglutarate and isochorismate are successively added to the cofactor before final cleavage of the product. We have determined a series of crystal structures of Mtb-MenD that map the binding of both substrates, visualizing each step in the MenD catalytic cycle, including both intermediates. ThDP binding induces a marked asymmetry between the coupled active sites of each dimer, and possible mechanisms of communication can be identified. The crystal structures also reveal conformational features of the two intermediates that facilitate reaction but prevent premature product release. These data fully map chemical space to inform early-stage drug discovery targeting MenD.
| + | |
| - | | + | |
| - | Structural Views along the Mycobacterium tuberculosis MenD Reaction Pathway Illuminate Key Aspects of Thiamin Diphosphate-Dependent Enzyme Mechanisms.,Jirgis EN, Bashiri G, Bulloch EM, Johnston JM, Baker EN Structure. 2016 Jul 6;24(7):1167-77. doi: 10.1016/j.str.2016.04.018. Epub 2016, Jun 9. PMID:27291649<ref>PMID:27291649</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5esd" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase]] | + | [[Category: Large Structures]] |
| - | [[Category: Baker, E N]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Bashiri, G]] | + | [[Category: Baker EN]] |
| - | [[Category: Bulloch, E M.M]] | + | [[Category: Bashiri G]] |
| - | [[Category: Jirgis, E N.M]] | + | [[Category: Bulloch EMM]] |
| - | [[Category: Johnston, J M]] | + | [[Category: Jirgis ENM]] |
| - | [[Category: 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexadiene-1-carboxylate synthase]] | + | [[Category: Johnston JM]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Menaquinone biosynthesis]]
| + | |
| - | [[Category: Mend]]
| + | |
| - | [[Category: Pyruvate oxidase family]]
| + | |
| - | [[Category: Thiamin-diphosphate dependent enzyme]]
| + | |
