Structural basis for glucose-6-phosphate activation of glycogen synthase

Journal Article · Mon Nov 22 04:00:00 EST 2010 · Proc. Natl. Acad. Sci. USA

DOI:https://doi.org/10.1073/pnas.1006340107· OSTI ID:1002839

Baskaran, Sulochanadevi; Roach, Peter J; DePaoli-Roach, Anna A; Hurley, Thomas D ^[1]

---

1. Indiana-Med

Regulation of the storage of glycogen, one of the major energy reserves, is of utmost metabolic importance. In eukaryotes, this regulation is accomplished through glucose-6-phosphate levels and protein phosphorylation. Glycogen synthase homologs in bacteria and archaea lack regulation, while the eukaryotic enzymes are inhibited by protein kinase mediated phosphorylation and activated by protein phosphatases and glucose-6-phosphate binding. We determined the crystal structures corresponding to the basal activity state and glucose-6-phosphate activated state of yeast glycogen synthase-2. The enzyme is assembled into an unusual tetramer by an insertion unique to the eukaryotic enzymes, and this subunit interface is rearranged by the binding of glucose-6-phosphate, which frees the active site cleft and facilitates catalysis. Using both mutagenesis and intein-mediated phospho-peptide ligation experiments, we demonstrate that the enzyme's response to glucose-6-phosphate is controlled by Arg583 and Arg587, while four additional arginine residues present within the same regulatory helix regulate the response to phosphorylation.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002839
• Journal Information: Proc. Natl. Acad. Sci. USA, Journal Name: Proc. Natl. Acad. Sci. USA Journal Issue: (41) ; 10, 2010 Vol. 107; ISSN PNASA6; ISSN 0027-8424
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
ARGININE
BACTERIA
CATALYSIS
CRYSTAL STRUCTURE
ENZYMES
GLYCOGEN
MUTAGENESIS
PHOSPHATASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROTEINS
REGULATIONS
RESIDUES
STORAGE
YEASTS