scholarly journals Tautomeric and anomeric specificity of allosteric activation of yeast pyruvate kinase by D-fructose 1,6-bisphosphate and its relevance in D-glucose catabolism

FEBS Letters ◽  
1976 ◽  
Vol 63 (1) ◽  
pp. 17-21 ◽  
Keyword(s):  
Pyruvate Kinase ◽  
Allosteric Activation ◽  
Glucose Catabolism ◽  
Anomeric Specificity ◽  
Fructose 1,6 Bisphosphate

scholarly journals Changes in the allosteric site of human liver pyruvate kinase upon activator binding include the breakage of an intersubunit cation–π bond

2019 ◽  
Vol 75 (6) ◽  
pp. 461-469 ◽  
Author(s):  
Jeffrey S. McFarlane ◽  
Trey A. Ronnebaum ◽  
Kathleen M. Meneely ◽  
Annemarie Chilton ◽  
Aron W. Fenton ◽  
...  
Keyword(s):  
Pyruvate Kinase ◽  
Functional Data ◽  
Human Liver ◽  
Phosphate Binding ◽  
Allosteric Site ◽  
Allosteric Activation ◽  
X Ray ◽  
Fructose 1,6 Bisphosphate ◽  
Open Position ◽  
Binding Loop

Human liver pyruvate kinase (hLPYK) converts phosphoenolpyruvate to pyruvate in the final step of glycolysis. hLPYK is allosterically activated by fructose-1,6-bisphosphate (Fru-1,6-BP). The allosteric site, as defined by previous structural studies, is located in domain C between the phosphate-binding loop (residues 444–449) and the allosteric loop (residues 527–533). In this study, the X-ray crystal structures of four hLPYK variants were solved to make structural correlations with existing functional data. The variants are D499N, W527H, Δ529/S531G (called GGG here) and S531E. The results revealed a conformational toggle between the open and closed positions of the allosteric loop. In the absence of Fru-1,6-BP the open position is stabilized, in part, by a cation–π bond between Trp527 and Arg538′ (from an adjacent monomer). In the S531E variant glutamate binds in place of the 6′-phosphate of Fru-1,6-BP in the allosteric site, leading to partial allosteric activation. Finally, the structure of the D499N mutant does not provide structural evidence for the previously observed allosteric activation of the D499N variant.

Anomeric specificity of yeast pyruvate kinase toward activation by D-fructose 1,6-bisphosphate

Biochemistry ◽  
1975 ◽  
Vol 14 (18) ◽  
pp. 4060-4063 ◽  
Author(s):  
Richard Fishbein ◽  
Patricia A. Benkovic ◽  
Stephen J. Benkovic
Keyword(s):  
Pyruvate Kinase ◽  
Anomeric Specificity ◽  
Fructose 1,6 Bisphosphate

scholarly journals Functional cross-talk between allosteric effects of activating and inhibiting ligands underlies PKM2 regulation

2018 ◽  
Author(s):  
Jamie A. Macpherson ◽  
Alina Theisen ◽  
Laura Masino ◽  
Louise Fets ◽  
Paul C. Driscoll ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
High Activity ◽  
Pyruvate Kinase ◽  
Cross Talk ◽  
Glycolytic Enzyme ◽  
Computational Framework ◽  
Allosteric Inhibitor ◽  
Fructose 1,6 Bisphosphate ◽  
Low Activity

ABSTRACTAllosteric regulation is central to the role of the glycolytic enzyme pyruvate kinase M2 (PKM2) in cellular metabolism. Multiple activating and inhibitory allosteric ligands regulate PKM2 activity by controlling the equilibrium between high activity tetramers and low activity dimers and monomers. However, it remains elusive how allosteric inputs upon simultaneous binding of different ligands are integrated to regulate PKM2 activity. Here, we show that, in the presence of the allosteric inhibitor L-phenylalanine (Phe), the activator fructose 1,6-bisphosphate (FBP) can induce PKM2 tetramerisation, but fails to maximally increase enzymatic activity. Guided by a new computational framework we developed to identify residues that mediate FBP-induced allostery, we generated two PKM2 mutants, A327S and C358A, in which activation by FBP remains intact but cannot be attenuated by Phe. Our findings demonstrate a role for residues involved in FBP-induced allostery in enabling the integration of allosteric input from Phe and reveal a mechanism that underlies the co-ordinate regulation of PKM2 activity by multiple allosteric ligands.

Partial purification and properties of pyruvate kinase and its regulatory role during lipid accumulation by the oleaginous yeast Rhodosporidium toruloides CBS 14

1985 ◽  
Vol 31 (5) ◽  
pp. 479-484 ◽  
Author(s):  
Christopher Thomas Evans ◽  
Colin Ratledge
Keyword(s):  
Pyruvate Kinase ◽  
Oleaginous Yeast ◽  
Lipid Production ◽  
Energy Charge ◽  
Rhodosporidium Toruloides ◽  
Regulatory Role ◽  
Relative Mass ◽  
Partial Purification ◽  
Wide Range ◽  
Fructose 1,6 Bisphosphate

Pyruvate kinase from the oleaginous yeast Rhodosporidium toruloides CBS 14 was partially purified and its properties investigated to determine its role during lipid production by this yeast. The enzyme (relative mass (Mr) = 190 000) showed a pH optimum of 8.0 and apparent Km values for K+, phosphoenolpyruvate (PEP), and ADP of 1.6 mM, 571 μM, and 120 μM, respectively. Enzyme activity was inhibited by citrate, isocitrate, ATP, GTP, and CTP and activated by fructose 1,6-bisphosphate, L-glutamate, and [Formula: see text] ions. Inhibition by citrate and ATP were both competitive with PEP with the Ki(citrate) = 340 μM and Ki(ATP) = 303 μM. The effect of ATP and cellular energy charge were critically dependent on the concentration of ADP present in the enzyme assay. Both L-glutamate and fructose 1,6-bisphosphate increased the affinity of the enzyme for both PEP and ADP and so were significant activators at nonsaturating substrate concentrations. [Formula: see text] ions increased the affinity of the enzyme for PEP, but not ADP. The modulation of pyruvate kinase activity by such a wide range of effectors is indicative of a major regulatory role in controlling the flux of carbon, through glycolysis, into lipid-synthesizing systems.

Allosteric activation of pyruvate kinase via NAD+ in rat liver cells

2001 ◽  
Vol 268 (14) ◽  
pp. 3943-3949 ◽  
Author(s):  
Anne Devin ◽  
Véronique Nogueira ◽  
Xavier Leverve ◽  
Bernard Guérin ◽  
Michel Rigoulet
Keyword(s):  
Pyruvate Kinase ◽  
Rat Liver ◽  
Liver Cells ◽  
Allosteric Activation ◽  
Rat Liver Cells
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