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PDBsum entry 3n1c
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References listed in PDB file
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Key reference
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Title
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The crystal complex of phosphofructokinase-2 of escherichia coli with fructose-6-Phosphate: kinetic and structural analysis of the allosteric ATP inhibition.
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Authors
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R.Cabrera,
M.Baez,
H.M.Pereira,
A.Caniuguir,
R.C.Garratt,
J.Babul.
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Ref.
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J Biol Chem, 2011,
286,
5774-5783.
[DOI no: ]
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PubMed id
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Abstract
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Substrate inhibition by ATP is a regulatory feature of the phosphofructokinases
isoenzymes from Escherichia coli (Pfk-1 and Pfk-2). Under gluconeogenic
conditions, the loss of this regulation in Pfk-2 causes substrate cycling of
fructose-6-phosphate (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
Å. 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 K(0.5) for fructose-6-P and a decrease in the apparent
k(cat) as a function of MgATP concentration. These effects occur simultaneously
with the induction of a sigmoidal kinetic behavior (n(H) of approximately 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, because these enzymes do not share a common ancestor.
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