|
|
| (One intermediate revision not shown.) |
| Line 3: |
Line 3: |
| | <StructureSection load='6o0j' size='340' side='right'caption='[[6o0j]], [[Resolution|resolution]] 2.35Å' scene=''> | | <StructureSection load='6o0j' size='340' side='right'caption='[[6o0j]], [[Resolution|resolution]] 2.35Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6o0j]] 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=6O0J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O0J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6o0j]] 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=6O0J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O0J FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DNA:1,4-DIHYDROXY-2-NAPHTHOIC+ACID'>DNA</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.35Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6o04|6o04]], [[6o0g|6o0g]], [[5ess|5ess]], [[5esu|5esu]], [[5eso|5eso]], [[5esd|5esd]], [[5ery|5ery]], [[5erx|5erx]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DNA:1,4-DIHYDROXY-2-NAPHTHOIC+ACID'>DNA</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TPP:THIAMINE+DIPHOSPHATE'>TPP</scene></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=6o0j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o0j OCA], [https://pdbe.org/6o0j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o0j RCSB], [https://www.ebi.ac.uk/pdbsum/6o0j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o0j 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=6o0j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o0j OCA], [http://pdbe.org/6o0j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o0j RCSB], [http://www.ebi.ac.uk/pdbsum/6o0j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o0j 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 == |
| Line 25: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase]] | |
| | [[Category: Large Structures]] | | [[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: Chuang, H]] | + | [[Category: Chuang H]] |
| - | [[Category: Ho, N A.T]] | + | [[Category: Ho NAT]] |
| - | [[Category: Jirgis, E M.N]] | + | [[Category: Jirgis EMN]] |
| - | [[Category: Johnston, J M]] | + | [[Category: Johnston JM]] |
| - | [[Category: Nigon, L V]] | + | [[Category: Nigon LV]] |
| - | [[Category: C-c bond ligation]]
| + | |
| - | [[Category: Decarboxylation]]
| + | |
| - | [[Category: Inhibitor complex]]
| + | |
| - | [[Category: Menaquinone biosynthesis]]
| + | |
| - | [[Category: Sephchc synthase]]
| + | |
| - | [[Category: Thdp dependent]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| Structural highlights
6o0j is a 4 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.35Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
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 (vitamin K2) plays a vital role in energy generation and environmental adaptation in many bacteria, including the human pathogen Mycobacterium tuberculosis (Mtb). Although menaquinone levels are known to be tightly linked to the cellular redox/energy status of the cell, the regulatory mechanisms underpinning this phenomenon are unclear. The first committed step in menaquinone biosynthesis is catalyzed by MenD, a thiamine diphosphate-dependent enzyme comprising three domains. Domains I and III form the MenD active site, but no function has yet been ascribed to domain II. Here, we show that the last cytosolic metabolite in the menaquinone biosynthesis pathway, 1,4-dihydroxy-2-naphthoic acid (DHNA), binds to domain II of Mtb-MenD and inhibits its activity. Using X-ray crystallography of four apo and cofactor-bound Mtb-MenD structures, along with several spectroscopy assays, we identified three arginine residues (Arg-97, Arg-277, and Arg-303) that are important for both enzyme activity and the feedback inhibition by DHNA. Among these residues Arg277 appeared to be particularly important for signal propagation from the allosteric site to the active site. This is the first evidence of feedback regulation of the menaquinone biosynthesis pathway in bacteria, identifying a protein-level regulatory mechanism that controls menaquinone levels within the cell and may therefore represent a good target for disrupting vitamin K2 biosynthesis in M. tuberculosis.
Allosteric regulation of menaquinone (vitamin K2) biosynthesis in the human pathogen Mycobacterium tuberculosis.,Bashiri G, Nigon LV, Jirgis ENM, Ho NAT, Stanborough T, Dawes SS, Baker EN, Bulloch EMM, Johnston JM J Biol Chem. 2020 Feb 6. pii: RA119.012158. doi: 10.1074/jbc.RA119.012158. PMID:32029475[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bashiri G, Nigon LV, Jirgis ENM, Ho NAT, Stanborough T, Dawes SS, Baker EN, Bulloch EMM, Johnston JM. Allosteric regulation of menaquinone (vitamin K2) biosynthesis in the human pathogen Mycobacterium tuberculosis. J Biol Chem. 2020 Feb 6. pii: RA119.012158. doi: 10.1074/jbc.RA119.012158. PMID:32029475 doi:http://dx.doi.org/10.1074/jbc.RA119.012158
|
