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| | <StructureSection load='6ito' size='340' side='right'caption='[[6ito]], [[Resolution|resolution]] 2.55Å' scene=''> | | <StructureSection load='6ito' size='340' side='right'caption='[[6ito]], [[Resolution|resolution]] 2.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ito]] 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=6ITO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ITO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ito]] 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=6ITO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ITO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene>, <scene name='pdbligand=R5P:RIBOSE-5-PHOSPHATE'>R5P</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]] 2.55Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5wsc|5wsc]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene>, <scene name='pdbligand=R5P:RIBOSE-5-PHOSPHATE'>R5P</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pyk, pykA, Rv1617, MTCY01B2.09 ([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=6ito FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ito OCA], [https://pdbe.org/6ito PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ito RCSB], [https://www.ebi.ac.uk/pdbsum/6ito PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ito 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/Pyruvate_kinase Pyruvate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.40 2.7.1.40] </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=6ito FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ito OCA], [http://pdbe.org/6ito PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ito RCSB], [http://www.ebi.ac.uk/pdbsum/6ito PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ito ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/KPYK_MYCTU KPYK_MYCTU] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6ito" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6ito" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Pyruvate kinase 3D structures|Pyruvate kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Myctu]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Pyruvate kinase]] | + | [[Category: Cai Q]] |
| - | [[Category: Cai, Q]] | + | [[Category: Dedon PC]] |
| - | [[Category: Dedon, P C]] | + | [[Category: El Sahili A]] |
| - | [[Category: Lescar, J]] | + | [[Category: Lescar J]] |
| - | [[Category: Mu, Y]] | + | [[Category: Mu Y]] |
| - | [[Category: Sahili, A El]]
| + | [[Category: Zhong W]] |
| - | [[Category: Zhong, W]] | + | |
| - | [[Category: Allostery]]
| + | |
| - | [[Category: Glycolysis]]
| + | |
| - | [[Category: Phospho transferase]]
| + | |
| - | [[Category: Synergism]]
| + | |
| - | [[Category: Tetramer]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
KPYK_MYCTU
Publication Abstract from PubMed
In response to the stress of infection, Mycobacterium tuberculosis (Mtb) reprograms its metabolism to accommodate nutrient and energetic demands in a changing environment. Pyruvate kinase (PYK) is an essential glycolytic enzyme in the phosphoenolpyruvate-pyruvate-oxaloacetate node that is a central switch point for carbon flux distribution. Here we show that the competitive binding of pentose monophosphate inhibitors or the activator glucose 6-phosphate (G6P) to MtbPYK tightly regulates the metabolic flux. Intriguingly, pentose monophosphates were found to share the same binding site with G6P. The determination of a crystal structure of MtbPYK with bound ribose 5-phosphate (R5P), combined with biochemical analyses and molecular dynamic simulations, revealed that the allosteric inhibitor pentose monophosphate increases PYK structural dynamics, weakens the structural network communication, and impairs substrate binding. G6P, on the other hand, primes and activates the tetramer by decreasing protein flexibility and strengthening allosteric coupling. Therefore, we propose that MtbPYK uses these differences in conformational dynamics to up- and down-regulate enzymic activity. Importantly, metabolome profiling in mycobacteria reveals a significant increase in the levels of pentose monophosphate during hypoxia, which provides insights into how PYK uses dynamics of the tetramer as a competitive allosteric mechanism to retard glycolysis and facilitate metabolic reprogramming toward the pentose-phosphate pathway for achieving redox balance and an anticipatory metabolic response in Mtb.
Pyruvate Kinase Regulates the Pentose-Phosphate Pathway in Response to Hypoxia in Mycobacterium tuberculosis.,Zhong W, Guo J, Cui L, Chionh YH, Li K, El Sahili A, Cai Q, Yuan M, Michels PAM, Fothergill-Gilmore LA, Walkinshaw MD, Mu Y, Lescar J, Dedon PC J Mol Biol. 2019 Aug 2. pii: S0022-2836(19)30484-X. doi:, 10.1016/j.jmb.2019.07.033. PMID:31381898[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhong W, Guo J, Cui L, Chionh YH, Li K, El Sahili A, Cai Q, Yuan M, Michels PAM, Fothergill-Gilmore LA, Walkinshaw MD, Mu Y, Lescar J, Dedon PC. Pyruvate Kinase Regulates the Pentose-Phosphate Pathway in Response to Hypoxia in Mycobacterium tuberculosis. J Mol Biol. 2019 Aug 2. pii: S0022-2836(19)30484-X. doi:, 10.1016/j.jmb.2019.07.033. PMID:31381898 doi:http://dx.doi.org/10.1016/j.jmb.2019.07.033
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