2Q8M

T-like Fructose-1,6-bisphosphatase from Escherichia coli with AMP, Glucose 6-phosphate, and Fructose 1,6-bisphosphate bound

Summary for 2Q8M

• Entry DOI: 10.2210/pdb2q8m/pdb
• Related: 2GQ1 2OWZ 2OX3
• Descriptor: Fructose-bisphosphatase, 6-O-phosphono-beta-D-glucopyranose, 1,6-di-O-phosphono-beta-D-fructofuranose, ... (7 entities in total)
• Functional Keywords: glycolysis, gluconeogenesis, bacteria, carbohydrate metabolism, diabetes, protein-protein interactions, proteobacteria, gram-negative, protein crystallography, heterotrophic, allosteric regulation, hydrolase
• Biological source: Shigella boydii
• Total number of polymer chains: 2
• Total formula weight: 76160.86

Authors

Hines, J.K.,Kruesel, C.E.,Fromm, H.J.,Honzatko, R.B. (deposition date: 2007-06-11, release date: 2007-06-19, Last modification date: 2024-10-30)

Primary citation

Hines, J.K.,Kruesel, C.E.,Fromm, H.J.,Honzatko, R.B.
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.
J.Biol.Chem., 282:24697-24706, 2007

PubMed Abstract: 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.

PubMed: 17567577
DOI: 10.1074/jbc.M703580200

Experimental method

X-RAY DIFFRACTION (2.05 Å)