5wsa

Pyruvate kinase (PYK) from Mycobacterium tuberculosis in complex with Oxalate and allosteric activator Glucose 6-Phosphate

spinqualitylabelsall models 5wsa, resolution 2.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5wsa 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 2.85Å Ligands: G6P, MG, OXL, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Pyruvate kinase 3D structures

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