A novel dual allosteric activation mechanism of Escherichia coli ADP-glucose pyrophosphorylase: the role of pyruvate

PLoS One. 2014 Aug 7;9(8):e103888. doi: 10.1371/journal.pone.0103888. eCollection 2014.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allosteric Site
  • Enzyme Activation
  • Escherichia coli / enzymology*
  • Fructosediphosphates / chemistry
  • Fructosediphosphates / metabolism
  • Glucose-1-Phosphate Adenylyltransferase / metabolism*
  • Glycogen / biosynthesis
  • Kinetics
  • Pyruvates / chemistry
  • Pyruvates / metabolism*
  • Substrate Specificity

Substances

  • Fructosediphosphates
  • Pyruvates
  • Glycogen
  • Glucose-1-Phosphate Adenylyltransferase
  • 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.