Structural highlights
FunctionPFKB_ECOLI Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.[1] Publication Abstract from PubMedSubstrate inhibition by ATP is a regulatory feature of the phosphofructokinases isoenzymes from E. coli (Pfk-1 and Pfk-2). Under gluconeogenic conditions, the loss of this regulation in Pfk-2 causes substrate cycling of fructose-6-P and futile consumption of ATP delaying growth. In the present work we have broached the mechanism of ATP-induced inhibition of Pfk-2 from both structural and kinetic perspectives. The crystal structure of Pfk-2 in complex with fructose-6-P is reported to a resolution of 2 A. The comparison of this structure with the previously reported inhibited form of the enzyme suggests a negative interplay between fructose-6-P binding and allosteric binding of MgATP. Initial velocity experiments show a linear increase of the apparent K0.5 for fructose-6-P and a decrease in the apparent kcat as a function of MgATP concentration. These effects occur simultaneously with the induction of a sigmoidal kinetic behavior (nH approx. 2). Differences and resemblances in the patterns of fructose-6-P binding and the mechanism of inhibition are discussed for Pfk-1 and Pfk-2, as an example of evolutionary convergence, since these enzymes do not share a common ancestor. The crystal complex of phosphofructokinase-2 of Escherichia coli with fructose-6-P: kinetic and structural analysis of the allosteric ATP inhibition.,Cabrera R, Baez M, Pereira HM, Caniuguir A, Garratt RC, Babul J J Biol Chem. 2010 Dec 8. PMID:21147773[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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