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| | ==Crystal Structure of APO MenD from M. tuberculosis - P212121== | | ==Crystal Structure of APO MenD from M. tuberculosis - P212121== |
| - | <StructureSection load='5ery' size='340' side='right' caption='[[5ery]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='5ery' size='340' side='right'caption='[[5ery]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ery]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ERY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ERY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ery]] 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=5ERY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ERY FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5erx|5erx]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">menD, Rv0555 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=5ery FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ery OCA], [https://pdbe.org/5ery PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ery RCSB], [https://www.ebi.ac.uk/pdbsum/5ery PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ery 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/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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ery FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ery OCA], [http://pdbe.org/5ery PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ery RCSB], [http://www.ebi.ac.uk/pdbsum/5ery PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ery 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase]] | + | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Baker, E N]] | + | [[Category: Baker EN]] |
| - | [[Category: Bashiri, G]] | + | [[Category: Bashiri G]] |
| - | [[Category: Bulloch, E M.M]] | + | [[Category: Bulloch EMM]] |
| - | [[Category: Jirgis, E N.M]] | + | [[Category: Jirgis ENM]] |
| - | [[Category: Johnston, J M]] | + | [[Category: Johnston JM]] |
| - | [[Category: 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexadiene-1-carboxylate synthase]]
| + | |
| - | [[Category: Menaquinone biosynthesis]]
| + | |
| - | [[Category: Mend]]
| + | |
| - | [[Category: Pyruvate oxidase family]]
| + | |
| - | [[Category: Thiamin-diphosphate dependent enzyme]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
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).
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jirgis EN, Bashiri G, Bulloch EM, Johnston JM, Baker EN. Structural Views along the Mycobacterium tuberculosis MenD Reaction Pathway Illuminate Key Aspects of Thiamin Diphosphate-Dependent Enzyme Mechanisms. Structure. 2016 Jul 6;24(7):1167-77. doi: 10.1016/j.str.2016.04.018. Epub 2016, Jun 9. PMID:27291649 doi:http://dx.doi.org/10.1016/j.str.2016.04.018
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