2q8m
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Allosteric activation of fructose-1,6-bisphosphatase (FBPase) from | + | Allosteric activation of fructose-1,6-bisphosphatase (FBPase) from Escherichia coli by phosphoenolpyruvate implies rapid feed-forward activation of gluconeogenesis in heterotrophic bacteria. But how do such bacteria rapidly down-regulate an activated FBPase in order to avoid futile cycling? Demonstrated here is the allosteric inhibition of E. coli FBPase by glucose 6-phosphate (Glc-6-P), the first metabolite produced upon glucose transport into the cell. FBPase undergoes a quaternary transition from the canonical R-state to a T-like state in response to Glc-6-P and AMP ligation. By displacing Phe(15), AMP binds to an allosteric site comparable with that of mammalian FBPase. Relative movements in helices H1 and H2 perturb allosteric activator sites for phosphoenolpyruvate. Glc-6-P binds to allosteric sites heretofore not observed in previous structures, perturbing subunits that in pairs form complete active sites of FBPase. Glc-6-P and AMP are synergistic inhibitors of E. coli FBPase, placing AMP/Glc-6-P inhibition in bacteria as a possible evolutionary predecessor to AMP/fructose 2,6-bisphosphate inhibition in mammalian FBPases. With no exceptions, signature residues of allosteric activation appear in bacterial sequences along with key residues of the Glc-6-P site. FBPases in such organisms may be components of metabolic switches that allow rapid changeover between gluconeogenesis and glycolysis in response to nutrient availability. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Structure of | + | Structure of inhibited fructose-1,6-bisphosphatase from Escherichia coli: distinct allosteric inhibition sites for AMP and glucose 6-phosphate and the characterization of a gluconeogenic switch., Hines JK, Kruesel CE, Fromm HJ, Honzatko RB, J Biol Chem. 2007 Aug 24;282(34):24697-706. Epub 2007 Jun 13. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17567577 17567577] |
[[Category: Fructose-bisphosphatase]] | [[Category: Fructose-bisphosphatase]] | ||
[[Category: Shigella boydii]] | [[Category: Shigella boydii]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Fromm, H | + | [[Category: Fromm, H J.]] |
| - | [[Category: Hines, J | + | [[Category: Hines, J K.]] |
| - | [[Category: Honzatko, R | + | [[Category: Honzatko, R B.]] |
| - | [[Category: Kruesel, C | + | [[Category: Kruesel, C E.]] |
[[Category: AMP]] | [[Category: AMP]] | ||
[[Category: BG6]] | [[Category: BG6]] | ||
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[[Category: x-ray diffraction]] | [[Category: x-ray diffraction]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:37:10 2008'' |
Revision as of 16:37, 21 February 2008
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T-like Fructose-1,6-bisphosphatase from Escherichia coli with AMP, Glucose 6-phosphate, and Fructose 1,6-bisphosphate bound
Overview
Allosteric activation of fructose-1,6-bisphosphatase (FBPase) from Escherichia coli by phosphoenolpyruvate implies rapid feed-forward activation of gluconeogenesis in heterotrophic bacteria. But how do such bacteria rapidly down-regulate an activated FBPase in order to avoid futile cycling? Demonstrated here is the allosteric inhibition of E. coli FBPase by glucose 6-phosphate (Glc-6-P), the first metabolite produced upon glucose transport into the cell. FBPase undergoes a quaternary transition from the canonical R-state to a T-like state in response to Glc-6-P and AMP ligation. By displacing Phe(15), AMP binds to an allosteric site comparable with that of mammalian FBPase. Relative movements in helices H1 and H2 perturb allosteric activator sites for phosphoenolpyruvate. Glc-6-P binds to allosteric sites heretofore not observed in previous structures, perturbing subunits that in pairs form complete active sites of FBPase. Glc-6-P and AMP are synergistic inhibitors of E. coli FBPase, placing AMP/Glc-6-P inhibition in bacteria as a possible evolutionary predecessor to AMP/fructose 2,6-bisphosphate inhibition in mammalian FBPases. With no exceptions, signature residues of allosteric activation appear in bacterial sequences along with key residues of the Glc-6-P site. FBPases in such organisms may be components of metabolic switches that allow rapid changeover between gluconeogenesis and glycolysis in response to nutrient availability.
About this Structure
2Q8M is a Single protein structure of sequence from Shigella boydii with , , , and as ligands. Active as Fructose-bisphosphatase, with EC number 3.1.3.11 Full crystallographic information is available from OCA.
Reference
Structure of inhibited fructose-1,6-bisphosphatase from Escherichia coli: distinct allosteric inhibition sites for AMP and glucose 6-phosphate and the characterization of a gluconeogenic switch., Hines JK, Kruesel CE, Fromm HJ, Honzatko RB, J Biol Chem. 2007 Aug 24;282(34):24697-706. Epub 2007 Jun 13. PMID:17567577
Page seeded by OCA on Thu Feb 21 18:37:10 2008
Categories: Fructose-bisphosphatase | Shigella boydii | Single protein | Fromm, H J. | Hines, J K. | Honzatko, R B. | Kruesel, C E. | AMP | BG6 | CL | FBP | MG | Allosteric regulation | Bacteria | Carbohydrate metabolism | Diabetes | Gluconeogenesis | Glycolysis | Gram-negative | Heterotrophic | Protein crystallography | Protein-protein interactions | Proteobacteria | X-ray diffraction
