Abstract
Fructose-1,6-bisphosphate activates ADP-glucose pyrophosphorylase and the synthesis of glycogen in Escherichia coli. Here, we show that although pyruvate is a weak activator by itself, it synergically enhances the fructose-1,6-bisphosphate activation. They increase the enzyme affinity for each other, and the combination increases Vmax, substrate apparent affinity, and decreases AMP inhibition. Our results indicate that there are two distinct interacting allosteric sites for activation. Hence, pyruvate modulates E. coli glycogen metabolism by orchestrating a functional network of allosteric regulators. We postulate that this novel dual activator mechanism increases the evolvability of ADP-glucose pyrophosphorylase and its related metabolic control.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allosteric Site
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Enzyme Activation
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Escherichia coli / enzymology*
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Fructosediphosphates / chemistry
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Fructosediphosphates / metabolism
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Glucose-1-Phosphate Adenylyltransferase / metabolism*
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Glycogen / biosynthesis
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Kinetics
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Pyruvates / chemistry
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Pyruvates / metabolism*
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Substrate Specificity
Substances
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Fructosediphosphates
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Pyruvates
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Glycogen
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Glucose-1-Phosphate Adenylyltransferase
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fructose-1,6-diphosphate
Grants and funding
This work was supported by grants to AAI from CONICET [PIP 112-201101-00438 and external collaboration], UNL [CAI+D’11 and Orientado], and ANPCyT [PICT’12 2439]; and to MAB from the National Science Foundation [MCB 1024945]. MDAD is Post-Doctoral Fellow from CONICET. AAI is Principal Investigator from the same Institution. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.