Structural Basis of Glycogen Biosynthesis Regulation in Bacteria

Structure. 2016 Sep 6;24(9):1613-22. doi: 10.1016/j.str.2016.06.023. Epub 2016 Aug 18.


ADP-glucose pyrophosphorylase (AGPase) catalyzes the rate-limiting step of bacterial glycogen and plant starch biosynthesis, the most common carbon storage polysaccharides in nature. A major challenge is to understand how AGPase activity is regulated by metabolites in the energetic flux within the cell. Here we report crystal structures of the homotetrameric AGPase from Escherichia coli in complex with its physiological positive and negative allosteric regulators, fructose-1,6-bisphosphate (FBP) and AMP, and sucrose in the active site. FBP and AMP bind to partially overlapping sites located in a deep cleft between glycosyltransferase A-like and left-handed β helix domains of neighboring protomers, accounting for the fact that sensitivity to inhibition by AMP is modulated by the concentration of the activator FBP. We propose a model in which the energy reporters regulate EcAGPase catalytic activity by intra-protomer interactions and inter-protomer crosstalk, with a sensory motif and two regulatory loops playing a prominent role.

MeSH terms

  • Adenosine Monophosphate / chemistry
  • Adenosine Monophosphate / metabolism
  • Allosteric Regulation
  • Amino Acid Sequence
  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Escherichia coli / enzymology
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Fructosediphosphates / chemistry
  • Fructosediphosphates / metabolism
  • Gene Expression Regulation, Bacterial*
  • Glucose-1-Phosphate Adenylyltransferase / chemistry*
  • Glucose-1-Phosphate Adenylyltransferase / genetics
  • Glucose-1-Phosphate Adenylyltransferase / metabolism
  • Glycogen / biosynthesis*
  • Models, Molecular
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sucrose / chemistry
  • Sucrose / metabolism


  • Escherichia coli Proteins
  • Fructosediphosphates
  • Recombinant Proteins
  • Adenosine Monophosphate
  • Sucrose
  • Glycogen
  • Glucose-1-Phosphate Adenylyltransferase
  • fructose-1,6-diphosphate