5wsa: Difference between revisions
New page: '''Unreleased structure''' The entry 5wsa is ON HOLD Authors: Zhong, W., Cai, Q., El Sahili, A., Lescar, J., Dedon, P.C. Description: Pyruvate kinase (PYK) from Mycobacterium tuberculo... |
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==Pyruvate kinase (PYK) from Mycobacterium tuberculosis in complex with Oxalate and allosteric activator Glucose 6-Phosphate== | |||
<StructureSection load='5wsa' size='340' side='right'caption='[[5wsa]], [[Resolution|resolution]] 2.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5wsa]] 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=5WSA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WSA FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.85Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G6P:ALPHA-D-GLUCOSE-6-PHOSPHATE'>G6P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=5wsa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wsa OCA], [https://pdbe.org/5wsa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wsa RCSB], [https://www.ebi.ac.uk/pdbsum/5wsa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wsa ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KPYK_MYCTU KPYK_MYCTU] | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:29215013</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Cai | <div class="pdbe-citations 5wsa" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Pyruvate kinase 3D structures|Pyruvate kinase 3D structures]] | ||
[[Category: Zhong | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis H37Rv]] | |||
[[Category: Cai Q]] | |||
[[Category: Dedon PC]] | |||
[[Category: El Sahili A]] | |||
[[Category: Lescar J]] | |||
[[Category: Zhong W]] | |||
Latest revision as of 19:52, 8 November 2023
Pyruvate kinase (PYK) from Mycobacterium tuberculosis in complex with Oxalate and allosteric activator Glucose 6-PhosphatePyruvate kinase (PYK) from Mycobacterium tuberculosis in complex with Oxalate and allosteric activator Glucose 6-Phosphate
Structural highlights
FunctionPublication Abstract from PubMedPyruvate 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 AlsoReferences
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