Crystal structure of glycogen synthase: Homologous enzymes catalyze glycogen synthesis and degradation

Unité de Biochimie Structurale, URA 2185 CNRS, Institut Pasteur, Paris, France.
The EMBO Journal (Impact Factor: 10.43). 09/2004; 23(16):3196-205. DOI: 10.1038/sj.emboj.7600324
Source: PubMed


Glycogen and starch are the major readily accessible energy storage compounds in nearly all living organisms. Glycogen is a very large branched glucose homopolymer containing about 90% alpha-1,4-glucosidic linkages and 10% alpha-1,6 linkages. Its synthesis and degradation constitute central pathways in the metabolism of living cells regulating a global carbon/energy buffer compartment. Glycogen biosynthesis involves the action of several enzymes among which glycogen synthase catalyzes the synthesis of the alpha-1,4-glucose backbone. We now report the first crystal structure of glycogen synthase in the presence and absence of adenosine diphosphate. The overall fold and the active site architecture of the protein are remarkably similar to those of glycogen phosphorylase, indicating a common catalytic mechanism and comparable substrate-binding properties. In contrast to glycogen phosphorylase, glycogen synthase has a much wider catalytic cleft, which is predicted to undergo an important interdomain 'closure' movement during the catalytic cycle. The structures also provide useful hints to shed light on the allosteric regulation mechanisms of yeast/mammalian glycogen synthases.

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    • "Interestingly, abundant POV-encoded PPP enzymes (for example, gnd, transketolase (tkt), and talC) (see Additional file 6: Table S4) represent all three enzymes whose metabolic flux is increased in starved E. coli[43]. Moreover, the glycogen biosynthetic gene (glgA), present in all viromes suggests that some viral infections trigger a starvation response in their hosts to redistribute carbon through non-glycolytic pathways [44,45]. "
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    Genome biology 11/2013; 14(11):R123. DOI:10.1186/gb-2013-14-11-r123 · 10.81 Impact Factor
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    • "We further demonstrated that the interaction between two regions within the SBDs (D(385e413) in D2 and D(564e604) in D3) and the CD, as well as the full starch binding capacity of the D2 domain are requisites for the full catalytic activity of SSIII [11] [20]. Besides the biochemical characterization, we had proposed a structural model of SSIII-CD that predicts a global structural similarity with the GS from Agrobacterium tumefaciens [21] [22]. Particularly , a fully conservation of the ADP-binding residues was found: residues participating in the binding of ADPGlc are evolutionary conserved in plants and algae [22]. "
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    Biochimie 06/2013; 95(10). DOI:10.1016/j.biochi.2013.06.009 · 2.96 Impact Factor
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    • "Glycogen metabolism-related genes and glycogen structure With the development of molecular biology, more and more effort has been put into the study of structural genes of glycogen metabolism and their influence on glycogen structure (Buschiazzo et al. 2004; Dauvillee et al. 2005; Alonso-Casajus et al. 2006; Ballicora et al. 2003; Binderup et al. 2000). The corresponding genes for enzymes of glycogen metabolism are glgC, glgA, glgB, glgP, glgX, respectively (Fig. 3). "
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