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| | ==Pyruvate kinase (PYK) from Mycobacterium tuberculosis in complex with Oxalate== | | ==Pyruvate kinase (PYK) from Mycobacterium tuberculosis in complex with Oxalate== |
| - | <StructureSection load='5ws8' size='340' side='right' caption='[[5ws8]], [[Resolution|resolution]] 2.62Å' scene=''> | + | <StructureSection load='5ws8' size='340' side='right'caption='[[5ws8]], [[Resolution|resolution]] 2.62Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ws8]] 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=5WS8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WS8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ws8]] 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=5WS8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WS8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</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]] 2.62Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5wrp|5wrp]], [[5ws9|5ws9]], [[5wsa|5wsa]], [[5wsb|5wsb]], [[5wsc|5wsc]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</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=5ws8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ws8 OCA], [https://pdbe.org/5ws8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ws8 RCSB], [https://www.ebi.ac.uk/pdbsum/5ws8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ws8 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=5ws8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ws8 OCA], [http://pdbe.org/5ws8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ws8 RCSB], [http://www.ebi.ac.uk/pdbsum/5ws8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ws8 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 5ws8" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5ws8" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Pyruvate kinase 3D structures|Pyruvate kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Myctu]] | + | [[Category: Large Structures]] |
| - | [[Category: Pyruvate kinase]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Cai, Q]] | + | [[Category: Cai Q]] |
| - | [[Category: Dedon, P C]] | + | [[Category: Dedon PC]] |
| - | [[Category: Lescar, J]] | + | [[Category: El Sahili A]] |
| - | [[Category: Sahili, A El]] | + | [[Category: Lescar J]] |
| - | [[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
Pyruvate kinase (PYK) is an essential glycolytic enzyme that controls glycolytic flux and is critical for ATP production in all organisms, with tight regulation by multiple metabolites. Yet the allosteric mechanisms governing PYK activity in bacterial pathogens are poorly understood. Here we report biochemical, structural and metabolomic evidence that Mycobacterium tuberculosis (Mtb) PYK uses AMP and glucose-6-phosphate (G6P) as synergistic allosteric activators that function as a molecular "OR logic gate" to tightly regulate energy and glucose metabolism. G6P was found to bind to a previously unknown site adjacent to the canonical site for AMP. Kinetic data and structural network analysis further show that AMP and G6P work synergistically as allosteric activators. Importantly, metabolome profiling in the Mtb surrogate, Mycobacterium bovis BCG, reveals significant changes in AMP and G6P levels during nutrient deprivation, which provides insights into how a PYK OR gate would function during the stress of Mtb infection.
Allosteric pyruvate kinase-based "logic gate" synergistically senses energy and sugar levels in Mycobacterium tuberculosis.,Zhong W, Cui L, Goh BC, Cai Q, Ho P, Chionh YH, Yuan M, Sahili AE, Fothergill-Gilmore LA, Walkinshaw MD, Lescar J, Dedon PC Nat Commun. 2017 Dec 7;8(1):1986. doi: 10.1038/s41467-017-02086-y. PMID:29215013[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhong W, Cui L, Goh BC, Cai Q, Ho P, Chionh YH, Yuan M, Sahili AE, Fothergill-Gilmore LA, Walkinshaw MD, Lescar J, Dedon PC. Allosteric pyruvate kinase-based "logic gate" synergistically senses energy and sugar levels in Mycobacterium tuberculosis. Nat Commun. 2017 Dec 7;8(1):1986. doi: 10.1038/s41467-017-02086-y. PMID:29215013 doi:http://dx.doi.org/10.1038/s41467-017-02086-y
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